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Endoscopic ultrasonography of the distal esophagus in achalasia
April 1995
Esophageal, Gastric, and Duodenal Disorders A59
Q ENDOSCOPIC ULTRASONOORAPHY OF THE DISTAL ESOPHAGUS IN ACHALASIA. J.O. Bertolino, P. Mambrini, P. Audibert, D. Zighed, O. Larroque, C. Bousti~re, T. Helbert, J. Salducci, J.C. Grimaud. Dept of Gastroenterology, North Hospital, Marscille, France
~THE CRITICAL CYSTEINE IN THE GASTRIC H,K ATPase FOR INHIBITION OF ACID SECRETION BY PROTON PUMP INHIBITORS.
The main advantage of endoscopic ultrasonogmphy for study of motor disorders of the esophagus is the ability to detect small tumors that can cause pseudoachalasia. Histological evidence of thickening of the muscle layer and ultmsonographie images of thickening of the hypoechogenic 4th layer ( corresponding to the muscle layer) has been inconsistently reported in patients with idiopathic achalasia. The purpose of this study was to assess the morphology and thickness of the lower esophagus wall by endoscopic ultrasonography in patients presenting idiopathic achalasia and to correlate findings with manometric data (lower esophageal sphincter (LOS) pressure). Patients and methods : Twelve patients (8 men, 4 women) with a mean age of 51 years (27 to 75 years) underwent endoscopic ultrasonography (Eehogastroscope Olympus, model EUM3) prior to treatment of achalasia diagnosed by manometry, barium swallow, and esophagoscopy. The wall of the lower esophagus was examined and measured 3 cm above the cardia at a frequency of 12 MHz. Results were compared to similar data obtained in a control group of 12 patients without esophageal disease, in whom endoscopy of the upper digestive tract and manometry were normal. Restilts : The structure of the esophageal wall was normal in the 14 patients with achalasia. The mean thickness of the wall of the lower esophagus was not significantly different in patients with achalasia and controls (3.0 + 0.1 mm versus 2.9 ± 0.1 mm). In patients with achalasia, manometry showed LOS pressure to be elevated in 8 cases and normal in 4 cases. There was no correlation between the thickness of the esophageal wall determined by endoscopic ultrasonography and LOS pressure determined by manometry. Conclusion : Significant thickening of the wall of the lower esophagus cannot be demonstrated by endoscopic ultrasonography in patients presenting idiopathic achalasia, regardless of thepressure of the LOS.
The currently prescribed proton pump inhibitor drugs, omeprazole, lansoprazole and pantoprazole are acid activated prodrugs that bind to cysteines in the alpha subunit of the active gastric H,K ATPase, This results in covalent inhibition of the acid transporting capacity of this polytopic integral membrane enzyme. Omeprazole binds to cysteine 813 or 822 in the 5th and 6th membrane spanning segments and cys 892 in the loop connecting TM7 and TM8, lansoprazole binds to cys 321 in TM3, cys 813/822 and also to cys 892, whereas pantoprazole binds to cys 813 and also to 822. In order to define which of these cysteines is important for inhibition of acid transport, intact hog gastric vesicles were incubated, under acid transporting conditions, with labelled drug in the presence of their respective sulfide derivatives, shown to slow inhibition. The labelled protein was digested and washed to povide the membrane spanning segment pairs connected by their extracellular loops. Following SDS page separation on tricine gradient gels, autoradiography and scanning of the autoradiogram allowed quantitation of the different radioactive bands. This provided a correlation of radioactivity with inhibition. In the case of omeprazole, cys 892 reacted more rapidly than cys 813/822, and reaction of the latter correlated with inhibition. In the case of lansoprazole, reaction occurred more rapidly with cys 321 and inhibition correlated more with binding to cys 813/822. In the case of pantoprazole, it was possible to distinguish binding to cys 813 and to 822 ( or vice versa) by the generation of a fragment beginning at position 793 in the alpha chain. Binding of pantoprazole to the same cysteine as with omeprazole and lansoprazole correlated with inhibition of enzyme activity. Accordingly cys 813 or 822 in the TM5/TM6 region of the membrane is the important target for these PPI's. Since modelling studies (Munson, K.B. in preparation) suggest that cysel3 is the more accessible residue, presumably cys 813 is the common and important amino acid target for these drugs.
EFFECT OF HELICOBACTER PYLORI ERADICATION ON THE HEALING O F NSAID-INDUCED GASTRIC AND/OR DUODENAL ULCERS G. Bianchi Forro, V. Imbesi, F. Montrone, I. Caruso Gastrointestinal Unit, L. Sacco Hospital, Milan, Italy.
EVALUATION OF 0MEPRAZOLE COUPLED WITH ANTIBIOTICS ON B.PYLOHI ERADICATION AND DUODENAL L~CER RECURRENCE G. BienchJ Porro, H. Lazzaronl, S, BargiEgis, E. 5olcis, H. Fiocca, M, Perego. Gastrointestinal Unit, L. Sacco Hospital, Milan, Italy.
Until today data reported in the literature are uncertain concerning the role cf H.pylori eradication on the healing of NSAID-induced duodenal or gastric ulcers. The aim of the present study was to evaluate whether H.pylori eradication has a positive influence on the acute healing of NSAID-induced gastroduodenal ulcers. |00 patients, suffering from rheumatoid arthritis or osteoarthrosis undergoing ant~-rheumatic treatment with diclofenac or naproxen, according [o their Hp status (evaluated through antrsl biopsy at the base control) were enrolledln this single-blind study. Thirty, H. pylori negative, were treated with omeprazole 20 mg bid for four weeks; H.pylori positive patients were rand0mfzed to receive two different treatments: 3~ patients, considered the control group, were treated with only omeprazole 20 mg bid for four weeks, while 36 received omeprazole 20 mE bid for ?nut weeks in combination with amoxicillin ] g bid for the first two weeks. Those unhealed after 4 weeks underwent a further 4 weeks' treatment with omeprazole. After four weeks' treatment with omeprazole, 21/30 patients(70%) in the H.pvlorl negative group were healed; 25/34 (74%) H.pyl0ri positive patients of those not treated with antibiotics and 27/36 (75%) of those who also received amoxlcillin w e r e also found to be healed. This healing rate reached 80Z in HP" patients, 82~ in eradicated patients and 83% in non-eradlcated patients after 8 weeks. Statistical analysis did not show anv significant difference. Tn conclusion, HP eradication (which was achieved in 61Z of the patients) did not influence the healing rate in our patients.
Marie Besancon, Alex Simon and George Sachs UCLA/Wadsworth VA, Los Angeles and Byk Gulden, Konstanz
The aim of
our study was to evaluate the efficacy
of
a
triple
association of omeprazole (0M) and antibiotics in the eradication of H.pyJori (HP) recurrence.
and
the
prevention
of
duodenal
ulcer
(DU)
J83 patients with active duodenal ulcer were randomized under double-bllnd conditions to receive OH 20 ~ for-four weeks, plus amoxicill~n 3 g daily and metronidazole i g daily in divided doses for two weeks (91 patients, Group A) or OM plus matching placebo (92 patients, Group 8). Endoscopic control took place ut 4 weeks, 2 months (for eradication) 6 and 12 months from the end of acute treatment. Two biopsies in the duoden,,~, 4 in the antrum and 3 in the gastric body were tsken at each endoscopic control for HP histological and urease research and for the evaluation of l) scores of gastritis and duodenitis. 2) total i~uneinflarmnatory cells, and 31 superficial epithelial lesions. After four weeks 84/86 (98%) of Group A were healed and 80/86 (93~) of Group B. There were 5 dropouts in Group A and 6 in Group B (2 patients in Group A and 3 in Group B for medical reasons). The percentage of eradication was 90% in Group A and I% iD Group B. After 12 months there was relapse in 4/64 (6%) of HP-patients and 56/73 (71%) of ~P+ patients. Complete suppression of gastroduodenitis activity and gastric surface epithelium lesions was observed in eradicated patients for the whole follow-up period. Total immunolnflammatorv ceils showed s significant but not complete decrease after 12 months as well. In non-eradicated biopsies we observed only a transient decrease of all scores at the end of therapy with the worsening of the same scores after 2 months.
Esophageal, Gastric, and Duodenal Disorders A59
Q ENDOSCOPIC ULTRASONOORAPHY OF THE DISTAL ESOPHAGUS IN ACHALASIA. J.O. Bertolino, P. Mambrini, P. Audibert, D. Zighed, O. Larroque, C. Bousti~re, T. Helbert, J. Salducci, J.C. Grimaud. Dept of Gastroenterology, North Hospital, Marscille, France
~THE CRITICAL CYSTEINE IN THE GASTRIC H,K ATPase FOR INHIBITION OF ACID SECRETION BY PROTON PUMP INHIBITORS.
The main advantage of endoscopic ultrasonogmphy for study of motor disorders of the esophagus is the ability to detect small tumors that can cause pseudoachalasia. Histological evidence of thickening of the muscle layer and ultmsonographie images of thickening of the hypoechogenic 4th layer ( corresponding to the muscle layer) has been inconsistently reported in patients with idiopathic achalasia. The purpose of this study was to assess the morphology and thickness of the lower esophagus wall by endoscopic ultrasonography in patients presenting idiopathic achalasia and to correlate findings with manometric data (lower esophageal sphincter (LOS) pressure). Patients and methods : Twelve patients (8 men, 4 women) with a mean age of 51 years (27 to 75 years) underwent endoscopic ultrasonography (Eehogastroscope Olympus, model EUM3) prior to treatment of achalasia diagnosed by manometry, barium swallow, and esophagoscopy. The wall of the lower esophagus was examined and measured 3 cm above the cardia at a frequency of 12 MHz. Results were compared to similar data obtained in a control group of 12 patients without esophageal disease, in whom endoscopy of the upper digestive tract and manometry were normal. Restilts : The structure of the esophageal wall was normal in the 14 patients with achalasia. The mean thickness of the wall of the lower esophagus was not significantly different in patients with achalasia and controls (3.0 + 0.1 mm versus 2.9 ± 0.1 mm). In patients with achalasia, manometry showed LOS pressure to be elevated in 8 cases and normal in 4 cases. There was no correlation between the thickness of the esophageal wall determined by endoscopic ultrasonography and LOS pressure determined by manometry. Conclusion : Significant thickening of the wall of the lower esophagus cannot be demonstrated by endoscopic ultrasonography in patients presenting idiopathic achalasia, regardless of thepressure of the LOS.
The currently prescribed proton pump inhibitor drugs, omeprazole, lansoprazole and pantoprazole are acid activated prodrugs that bind to cysteines in the alpha subunit of the active gastric H,K ATPase, This results in covalent inhibition of the acid transporting capacity of this polytopic integral membrane enzyme. Omeprazole binds to cysteine 813 or 822 in the 5th and 6th membrane spanning segments and cys 892 in the loop connecting TM7 and TM8, lansoprazole binds to cys 321 in TM3, cys 813/822 and also to cys 892, whereas pantoprazole binds to cys 813 and also to 822. In order to define which of these cysteines is important for inhibition of acid transport, intact hog gastric vesicles were incubated, under acid transporting conditions, with labelled drug in the presence of their respective sulfide derivatives, shown to slow inhibition. The labelled protein was digested and washed to povide the membrane spanning segment pairs connected by their extracellular loops. Following SDS page separation on tricine gradient gels, autoradiography and scanning of the autoradiogram allowed quantitation of the different radioactive bands. This provided a correlation of radioactivity with inhibition. In the case of omeprazole, cys 892 reacted more rapidly than cys 813/822, and reaction of the latter correlated with inhibition. In the case of lansoprazole, reaction occurred more rapidly with cys 321 and inhibition correlated more with binding to cys 813/822. In the case of pantoprazole, it was possible to distinguish binding to cys 813 and to 822 ( or vice versa) by the generation of a fragment beginning at position 793 in the alpha chain. Binding of pantoprazole to the same cysteine as with omeprazole and lansoprazole correlated with inhibition of enzyme activity. Accordingly cys 813 or 822 in the TM5/TM6 region of the membrane is the important target for these PPI's. Since modelling studies (Munson, K.B. in preparation) suggest that cysel3 is the more accessible residue, presumably cys 813 is the common and important amino acid target for these drugs.
EFFECT OF HELICOBACTER PYLORI ERADICATION ON THE HEALING O F NSAID-INDUCED GASTRIC AND/OR DUODENAL ULCERS G. Bianchi Forro, V. Imbesi, F. Montrone, I. Caruso Gastrointestinal Unit, L. Sacco Hospital, Milan, Italy.
EVALUATION OF 0MEPRAZOLE COUPLED WITH ANTIBIOTICS ON B.PYLOHI ERADICATION AND DUODENAL L~CER RECURRENCE G. BienchJ Porro, H. Lazzaronl, S, BargiEgis, E. 5olcis, H. Fiocca, M, Perego. Gastrointestinal Unit, L. Sacco Hospital, Milan, Italy.
Until today data reported in the literature are uncertain concerning the role cf H.pylori eradication on the healing of NSAID-induced duodenal or gastric ulcers. The aim of the present study was to evaluate whether H.pylori eradication has a positive influence on the acute healing of NSAID-induced gastroduodenal ulcers. |00 patients, suffering from rheumatoid arthritis or osteoarthrosis undergoing ant~-rheumatic treatment with diclofenac or naproxen, according [o their Hp status (evaluated through antrsl biopsy at the base control) were enrolledln this single-blind study. Thirty, H. pylori negative, were treated with omeprazole 20 mg bid for four weeks; H.pylori positive patients were rand0mfzed to receive two different treatments: 3~ patients, considered the control group, were treated with only omeprazole 20 mg bid for four weeks, while 36 received omeprazole 20 mE bid for ?nut weeks in combination with amoxicillin ] g bid for the first two weeks. Those unhealed after 4 weeks underwent a further 4 weeks' treatment with omeprazole. After four weeks' treatment with omeprazole, 21/30 patients(70%) in the H.pvlorl negative group were healed; 25/34 (74%) H.pyl0ri positive patients of those not treated with antibiotics and 27/36 (75%) of those who also received amoxlcillin w e r e also found to be healed. This healing rate reached 80Z in HP" patients, 82~ in eradicated patients and 83% in non-eradlcated patients after 8 weeks. Statistical analysis did not show anv significant difference. Tn conclusion, HP eradication (which was achieved in 61Z of the patients) did not influence the healing rate in our patients.
Marie Besancon, Alex Simon and George Sachs UCLA/Wadsworth VA, Los Angeles and Byk Gulden, Konstanz
The aim of
our study was to evaluate the efficacy
of
a
triple
association of omeprazole (0M) and antibiotics in the eradication of H.pyJori (HP) recurrence.
and
the
prevention
of
duodenal
ulcer
(DU)
J83 patients with active duodenal ulcer were randomized under double-bllnd conditions to receive OH 20 ~ for-four weeks, plus amoxicill~n 3 g daily and metronidazole i g daily in divided doses for two weeks (91 patients, Group A) or OM plus matching placebo (92 patients, Group 8). Endoscopic control took place ut 4 weeks, 2 months (for eradication) 6 and 12 months from the end of acute treatment. Two biopsies in the duoden,,~, 4 in the antrum and 3 in the gastric body were tsken at each endoscopic control for HP histological and urease research and for the evaluation of l) scores of gastritis and duodenitis. 2) total i~uneinflarmnatory cells, and 31 superficial epithelial lesions. After four weeks 84/86 (98%) of Group A were healed and 80/86 (93~) of Group B. There were 5 dropouts in Group A and 6 in Group B (2 patients in Group A and 3 in Group B for medical reasons). The percentage of eradication was 90% in Group A and I% iD Group B. After 12 months there was relapse in 4/64 (6%) of HP-patients and 56/73 (71%) of ~P+ patients. Complete suppression of gastroduodenitis activity and gastric surface epithelium lesions was observed in eradicated patients for the whole follow-up period. Total immunolnflammatorv ceils showed s significant but not complete decrease after 12 months as well. In non-eradicated biopsies we observed only a transient decrease of all scores at the end of therapy with the worsening of the same scores after 2 months.