Digestive Diseases and Sciences, Vot. 37, No. 8 (August 1992), pp. 1302-1309
LETTERS TO THE EDITOR
H2-RECEPTOR ANTAGONIST NONRESPONDERS AND OMEPRAZOLE
Department of Gastroenterology
To The Editor: We read the letter to the editor by V. Savarino et al (Dig Dis Sci 36:1172-1173, 1991) considering some aspects of inadequate pharmacodynamic effects of H2-receptor antagonists and omeprazole. In similar studies we found a higher frequency of patients with inadequate antisecretory response to H2-receptor blockers among patients with cirrhosis of the liver, compared to subjects with normal liver function (1). Nighttime intragastric pH was continuously monitored, and normal response was defined as a rise in the intragastric pH above 4.0 for more than 6 hr following the oral dose at 6 PM. In addition, plasma levels of the drugs were monitored to test for altered pharmacokinetics. In all subjects plasma concentrations of ranitidine were in a range where acid secretion should be suppressed. Thus, pharmacokinetic factors did not account for the inadequate response. Only in a few patients of both groups could the inadequate response to 300 mg of ranitidine be corrected by increasing the dose of the ranitidine to 900 mg (2) or by the addition of 50 mg of pirenzepine (3) or 400 p~g of misoprostol (4). Since intragastric pH is also affected by gastric emptying, we determined gastric emptying of 300 ml of orange juice labeled with 99mTC Solco Nanocoll. Gastric emptying was not delayed in any of the nonresponders, and therefore it would be very unlikely that gastric motility plays a role in the nonresponse to H2-receptor antagonists (5). Even though it appears possible to overcome the inadequate response of patients, omeprazole may be the drug of choice in patients with inadequate antisecretory response to H2-receptor antagonists. In contrast to 300 mg ranitidine, which, despite plasma levels 2 and 4 hr after intake of 762 --- 431 and 802 --- 668 ng/ml, respectively, resulted in a rise of the nighttime intragastric pH above 4 only for 1.8 --- 1.7 hr, the intragastric pH was above 4 for 10.1 +-2.4 of 12 hr during the night (P < 0.001) in 16 cirrhotics during treatment with 40 mg omeprazole (6). The omeprazole plasma levels were 611 --- 323 and 881 + 533 ng/ml after 2 and 4 hr respectively. In our study we demonstrated that the H2-blocker resistance in cirrhotics could be overcome by 40 mg of omeprazole.
1302
S. WALKER G. TREIBER A. SAREM-ASLANI
Department of Clinical Chemistry U. KLOTZ
Department of Clinical Pharmacology Robert-Bosch-Krankenhaus Stuttgart, Germany REFERENCES 1. Walker S, Krishna DR, Klotz U, Bode JC: Frequent nonresponse to histamine H2-receptor antagonists in cirrhotics. Gut 30:1105-1109, 1989 2. Walker S, Klotz U: Effect of 900 mg of ranitidine on the nocturnal intragastric acidity in non-responders to 300 mg of ranitidine. Eur J Gastroenterol Hepatol 2:33-36, 1990 3. Walker S, Klotz U, Bode JC: Combined effect of pirenzepine and ranitidine on the nocturnal intragastric pH in nonresponders to ranitidine. Z Gastroenterol 28:379-382, 1990 4. Walker S, Sarem-Aslani A, Treiber G, Klotz U, Bode JC: Addition of misoprostol to ranitidine in non-responders to H2-blockers and pirenzepine. Neth J Med 38:18-23, 1991 5. Walker S, Meinke J, Klotz U, Treiber G, Bode JC: Gastric emptying in non-responders to H2-receptor antagonists. Klin Wochenschr 68:959-963, 1990 6. Walker S, Sarem-Aslani A, Treiber G, Klotz U, Bode JC: Effect of omeprazole on nocturnal intragastric pH in cirrhotics not responding to ranitidine. Digestion 48:179-184, 1991
NEW PC-BASED PROGRAM TO CALCULATE GASTRIC SECRETION AND EMPTYING USING A MARKER DILUTION TECHNIQUE To The Editor: Measurement of gastric acid output is important both from a clinical and physiological standpoint. Clinically, it has been shown that the healing rate of peptic ulcer disease is related to the degree of acid suppression (1) and determination of acid output has been used to calculate the effective dose of histamine H 2 antagonists or H +,K + -ATPase inhibitors (2, 3). Recently, metanalysis of data obtained with 24-hr intragastric pH monitoring has suggested that this type of approach may be useful (4). In addition, studies of the pharmacodynamics of these medications should be based on reliable determination of acid output, because these measurements are more easily quantifiable than intragastric pH. From a physiological standpoint, evaluation of the role of peptides that stimulate or inhibit acid output Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
0163-2116/92/0800-1302506.50/09 1992PlenumPublishingCorporation
LETTERS TO THE EDITOR require precise determination of gastric secretion while causing as little disturbance as possible of the normal regulatory feedback mechanisms. In both types of studies, concurrent measurement of fasting and postprandial emptying of fluids and acids may help in the understanding of gastric pathophysiology (5). A number of methods exist to determine basal and pentagastrin- or histalog-stimulated acid output, but none will be valid in all situations. The simplest method relies on continuous aspiration of the gastric contents through a double-lumen tube. However, it is advisable to correct for pyloric losses by concurrently and continuously infusing a nonabsorbable marker. Following meals, this method cannot be used, and other methods have been devised. These are the intragastric titration technique, the intragastric marker dilution technique, and the intraduodenal marker dilution technique. The intragastric titration method relies on the addition of alkali to the stomach contents to maintain a pH of 4 or 7 (6). This method has two limitations, which result in overestimation of acid output (7, 8): continuous mixing of the gastric contents requires forceful aspirations and reinjection of fluids and particles, creating mechanical stimulation of acid output. In addition, maintaining the pH at an artificial level interferes with normal feedback regulation of acid output and concurrent gastric emptying. The intragastric marker dilution technique requires only serial samplings of intragastric contents before and after injection of a marker. It permits concurrent measurement of gastric emptying, but this method can only be applied during fasting and after liquid meals (9). The intraduodenal marker dilution technique also allows concurrent measurement of acid output and of gastric emptying, and it may be applied after mixed solid and liquid meals (10). The method is based on dilution techniques previously developed to measure propulsion of fluids in the jejunum, and it has been extensively used by Malagelada et al (11). However, positioning of the tube in the duodenum requires radiography, perfusion of the duodenum with saline may modify gastric emptying and secretion, and a number of assumptions have to be made, which may entail nonnegligible errors (12). Thus, each of the techniques currently available to measure acid output may be applied to the study of specific questions, although no completely satisfactory method is currently available. Digestive Diseases and Sciences, Vol. 37, No. e (August 1992)
However, when gastric acid output is to be measured in response to secretagogues or to liquid meals, and if one is concerned about possible modifications of normal gastric physiology and about radiation exposure, we believe that the marker dilution technique is preferable. This method has been used successfully in animals (13-15), as well as in infants (16) and adult volunteers and patients (9, 17-19). Until recently, the main limitation of this technique was that many clinicians and gastrointestinal physiologists did not have access to a mainframe computer on which the program could be run. If available, this option was often costly and awkward. Therefore, we have adapted the original FORTRAN computer program to calculate gastric emptying and gastric secretion on an IBM PC or compatible. The results provided by this program have been compared with those obtained using a PDP-10 computer (DCRT, NIH, Bethesda, Maryland). No numerical differences were observed up to the seventh decimal point, and the speed of execution is equivalent on a 286, 16-MHz PC. The size of this program is only 64 K, and it may be run from a floppy diskette. It will be provided upon request and telephone support will be available if necessary. It is expected that this new software will facilitate the diffusion of the intragastric marker dilution method and that it will foster its application to the study of various physiological and clinical questions where a precise measurement of gastric secretion and gastric emptying of liquids is required. ANDRE DUBOIS, M D , PHD
MARY MIZRAHI, MS Laboratory of Gastrointestinal and Liver Studies Digestive Diseases Division Department of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland 20814 REFERENCES 1. Rune S: The relationship between acid reduction and rate of ulcer healing. Scand J Gastroenterol Suppl 155:12-15, 1988 2. Santoro E, Morucci P, Idotta G, Scutari F: Ulcere duodenal, etude de la secretion gastrique et traitement rationnel par famotidine a doses differentes. Ann Gastroenterol Hepatol 25:211-214, 1989 3. Collen MJ, Stanczak VJ, Ciarleglio CA: Refractory duodenal ulcers (nonhealing duodenal ulcers with standard doses of antisecretory medication). Dig Dis Sci 34:233-237, 1989 4. Burget DW, Chiverton SG, Hunt RH: Is there an optimal
1303
LETTERS TO T H E EDITOR degree of acid suppression for healing of duodenal ulcers? Gastroenterology 99:345-351, 1990 5. Dubois A: Gastric emptying of liquids should not be studied independently from gastric secretion. In Functional Disorders of the Gastrointestinal Tract. W Chey (ed). New York, Raven Press, 1983, pp 151-155 6. Fortran JS, Walsh JH: Gastric acid secretion rate and buffer contents of the stomach after eating results in normal subjects and in patients with duodenal ulcer. J Clin Invest 52:645-657, 1973 7. Halter F, Keller M: A comparison between intragastric titration and gastric aspiration under basal conditions and after food or pentagastrin stimulation. Am J Dig Dis 23:723729, 1978 8. Feldman M: Comparison of acid secretion rates measured by gastric aspiration and by in vivo intragastric titration in healthy human subjects. Gastroenterology 76:954-957, 1979 9. Dubois A, Van Eerdewegh P, Gardner JD: Gastric emptying and secretion in Zollinger-Ellison syndrome. J Clin Invest 59:255-263, 1977 10. Go VLW, Hoffman AF, Summerskill WHJ: Simultaneous measurements of total pancreatic, biliary, and gastric outputs in man using a perfusion technique. Gastroenterology 58:321-328, 1970 11. Malagelada JR, Longstreth GF, Summerskill WHJ, Go VLW: Measurement of gastric functions during digestion of ordinary solid meals in man. Gastroenterology 70:203-210, 1976 12. Dubois A: Methods for studying propulsion and retropulsion of the alimentary tract contents. In Techniques in the Life Sciences. DA Titchen (ed). Amsterdam, Elsevier North Holland, 1982, p 202/1-18 13. Dubois A, Natelson BH, Van Eerdewegh P, Gardner JD: Gastric emptying and secretion in the rhesus monkey. Am J Physiol 232:EI86-E192, 1977 14. Batzri S, Harmon JW, Dubois A, Moskowitz D, Weichbrodt R, Rich NM: A new in vivo method for repeatedly studying gastric acid secretion and other secretory parameters in awake guinea pig. J Surg Res 43:398-405, 1987 15. Dorval ED, Mueller GP, Eng RR, Durakovic A, Conklin JJ, Dubois A: Effect of ionizing radiation on gastric secretion and gastric motility in monkeys. Gastroenterol 89:374-380, 1985 16. Hyman PE, Abrams C, Dubois A: Effect of metoclopramide and bethanechol on gastric emptying in infants. Pediatr Res 19:1029-1032, 1985 17. Dubois A, Castell DO: Abnormal gastric emptying response to pentagastrin in duodenal ulcer disease. Dig Dis Sci 26:292-296, 1981 18. Sasaki H, Nagulesparan M, Samloff IM, Straus E, Sievers ME, Dubois A: Low acid output in Pima Indians: A possible cause for the rarity of duodenal ulcer in this population. Dig Dis Sci 29:785-789, 1984 19. Cherner JA, Jensen RT, Dubois A, O'Dorisio TM, Gardner JD, Metcalfe DD: Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. Gastroenterology 95:657-667, 1988
1304
AUTOIMMUNE GASTRITIS: IS Helicobacter pylori A M E R E L Y C O M M E N S A L O R A PATHOGENIC AGENT? To The Editor: We h a v e read with great interest the p a p e r by O r m a n d et al (1) regarding the p r e v a l e n c e of Helicobacter pylori in s o m e specific f o r m s of chronic gastritis (ie, eosinophilic, C r o h n ' s , and M e n e t r i e r ' s gastritis). N o n e of the patients with specific f o r m s o f gastritis s h o w e d evidence o f H. pylori infection c o m p a r e d with the 71% o f the patients with chronic nonspecific gastritis. The authors concluded that the results o f the study " a d d further support to the accumulating evidence that H. pylori plays a pathogenic role in chronic nonspecific gastritis." To determine the p r e v a l e n c e of H. pylori in a further f o r m of specific chronic gastritis, we h a v e evaluated 16 patients (4 males and 12 females; m e a n age 64 years, range 5 5 - 8 0 years) with a u t o i m m u n e gastritis. All patients w e r e diagnosed as having a u t o i m m u n e gastritis on the basis of the p r e s e n c e o f p a r i e t a l cell a n t i b o d i e s , p e n t a g a s t r i n - r e s i s t a n t achlorhydria at gastric analysis, and diffuse fundal a t r o p h y by histological examination in repeated multiple biopsies; no hematological findings consistent with pernicious anemia w e r e detected. E a c h patient u n d e r w e n t u p p e r gastrointestinal endoscopy, and multiple biopsies in fundus, body, and antrum were m a d e (mean four samples, range three to five, in each region) b y separate sterile forceps. Histological specimens were stained with h e m a t o x ylin-eosin to study gastritis and with G i e m s a to search for H. pylori. Twelve patients were found to b e infected b y H. pylori. Biopsies f r o m fundus and b o d y showed the p r e s e n c e of H. pylori in both regions in all cases. The examination of the biopsies f r o m antrum detected chronic atrophic gastritis with H. pylori infection in seven cases and superficial gastritis in the remaining five patients, two of w h o m also showed H. pylori infection. In the four H. pylori-negative patients, the antral specimens revealed chronic atrophic gastritis in two and superficial gastritis in the other two patients. The results are s u m m a r i z e d in Table 1. The results of this study on H. priori infection in a u t o i m m u n e gastritis patients confirm those previously reported b y us in a smaller series (2), showing a p r e v a l e n c e of about 70%. Other authors described a lesser infection rate ranging f r o m 3 to 21% (3-6), nevertheless some others reported a p r e v a l e n c e Digestive Diseases and Sciences, Vol.37, No. 8 (August 1992)
LETTERS TO THE EDITOR
H2-RECEPTOR ANTAGONIST NONRESPONDERS AND OMEPRAZOLE
Department of Gastroenterology
To The Editor: We read the letter to the editor by V. Savarino et al (Dig Dis Sci 36:1172-1173, 1991) considering some aspects of inadequate pharmacodynamic effects of H2-receptor antagonists and omeprazole. In similar studies we found a higher frequency of patients with inadequate antisecretory response to H2-receptor blockers among patients with cirrhosis of the liver, compared to subjects with normal liver function (1). Nighttime intragastric pH was continuously monitored, and normal response was defined as a rise in the intragastric pH above 4.0 for more than 6 hr following the oral dose at 6 PM. In addition, plasma levels of the drugs were monitored to test for altered pharmacokinetics. In all subjects plasma concentrations of ranitidine were in a range where acid secretion should be suppressed. Thus, pharmacokinetic factors did not account for the inadequate response. Only in a few patients of both groups could the inadequate response to 300 mg of ranitidine be corrected by increasing the dose of the ranitidine to 900 mg (2) or by the addition of 50 mg of pirenzepine (3) or 400 p~g of misoprostol (4). Since intragastric pH is also affected by gastric emptying, we determined gastric emptying of 300 ml of orange juice labeled with 99mTC Solco Nanocoll. Gastric emptying was not delayed in any of the nonresponders, and therefore it would be very unlikely that gastric motility plays a role in the nonresponse to H2-receptor antagonists (5). Even though it appears possible to overcome the inadequate response of patients, omeprazole may be the drug of choice in patients with inadequate antisecretory response to H2-receptor antagonists. In contrast to 300 mg ranitidine, which, despite plasma levels 2 and 4 hr after intake of 762 --- 431 and 802 --- 668 ng/ml, respectively, resulted in a rise of the nighttime intragastric pH above 4 only for 1.8 --- 1.7 hr, the intragastric pH was above 4 for 10.1 +-2.4 of 12 hr during the night (P < 0.001) in 16 cirrhotics during treatment with 40 mg omeprazole (6). The omeprazole plasma levels were 611 --- 323 and 881 + 533 ng/ml after 2 and 4 hr respectively. In our study we demonstrated that the H2-blocker resistance in cirrhotics could be overcome by 40 mg of omeprazole.
1302
S. WALKER G. TREIBER A. SAREM-ASLANI
Department of Clinical Chemistry U. KLOTZ
Department of Clinical Pharmacology Robert-Bosch-Krankenhaus Stuttgart, Germany REFERENCES 1. Walker S, Krishna DR, Klotz U, Bode JC: Frequent nonresponse to histamine H2-receptor antagonists in cirrhotics. Gut 30:1105-1109, 1989 2. Walker S, Klotz U: Effect of 900 mg of ranitidine on the nocturnal intragastric acidity in non-responders to 300 mg of ranitidine. Eur J Gastroenterol Hepatol 2:33-36, 1990 3. Walker S, Klotz U, Bode JC: Combined effect of pirenzepine and ranitidine on the nocturnal intragastric pH in nonresponders to ranitidine. Z Gastroenterol 28:379-382, 1990 4. Walker S, Sarem-Aslani A, Treiber G, Klotz U, Bode JC: Addition of misoprostol to ranitidine in non-responders to H2-blockers and pirenzepine. Neth J Med 38:18-23, 1991 5. Walker S, Meinke J, Klotz U, Treiber G, Bode JC: Gastric emptying in non-responders to H2-receptor antagonists. Klin Wochenschr 68:959-963, 1990 6. Walker S, Sarem-Aslani A, Treiber G, Klotz U, Bode JC: Effect of omeprazole on nocturnal intragastric pH in cirrhotics not responding to ranitidine. Digestion 48:179-184, 1991
NEW PC-BASED PROGRAM TO CALCULATE GASTRIC SECRETION AND EMPTYING USING A MARKER DILUTION TECHNIQUE To The Editor: Measurement of gastric acid output is important both from a clinical and physiological standpoint. Clinically, it has been shown that the healing rate of peptic ulcer disease is related to the degree of acid suppression (1) and determination of acid output has been used to calculate the effective dose of histamine H 2 antagonists or H +,K + -ATPase inhibitors (2, 3). Recently, metanalysis of data obtained with 24-hr intragastric pH monitoring has suggested that this type of approach may be useful (4). In addition, studies of the pharmacodynamics of these medications should be based on reliable determination of acid output, because these measurements are more easily quantifiable than intragastric pH. From a physiological standpoint, evaluation of the role of peptides that stimulate or inhibit acid output Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
0163-2116/92/0800-1302506.50/09 1992PlenumPublishingCorporation
LETTERS TO THE EDITOR require precise determination of gastric secretion while causing as little disturbance as possible of the normal regulatory feedback mechanisms. In both types of studies, concurrent measurement of fasting and postprandial emptying of fluids and acids may help in the understanding of gastric pathophysiology (5). A number of methods exist to determine basal and pentagastrin- or histalog-stimulated acid output, but none will be valid in all situations. The simplest method relies on continuous aspiration of the gastric contents through a double-lumen tube. However, it is advisable to correct for pyloric losses by concurrently and continuously infusing a nonabsorbable marker. Following meals, this method cannot be used, and other methods have been devised. These are the intragastric titration technique, the intragastric marker dilution technique, and the intraduodenal marker dilution technique. The intragastric titration method relies on the addition of alkali to the stomach contents to maintain a pH of 4 or 7 (6). This method has two limitations, which result in overestimation of acid output (7, 8): continuous mixing of the gastric contents requires forceful aspirations and reinjection of fluids and particles, creating mechanical stimulation of acid output. In addition, maintaining the pH at an artificial level interferes with normal feedback regulation of acid output and concurrent gastric emptying. The intragastric marker dilution technique requires only serial samplings of intragastric contents before and after injection of a marker. It permits concurrent measurement of gastric emptying, but this method can only be applied during fasting and after liquid meals (9). The intraduodenal marker dilution technique also allows concurrent measurement of acid output and of gastric emptying, and it may be applied after mixed solid and liquid meals (10). The method is based on dilution techniques previously developed to measure propulsion of fluids in the jejunum, and it has been extensively used by Malagelada et al (11). However, positioning of the tube in the duodenum requires radiography, perfusion of the duodenum with saline may modify gastric emptying and secretion, and a number of assumptions have to be made, which may entail nonnegligible errors (12). Thus, each of the techniques currently available to measure acid output may be applied to the study of specific questions, although no completely satisfactory method is currently available. Digestive Diseases and Sciences, Vol. 37, No. e (August 1992)
However, when gastric acid output is to be measured in response to secretagogues or to liquid meals, and if one is concerned about possible modifications of normal gastric physiology and about radiation exposure, we believe that the marker dilution technique is preferable. This method has been used successfully in animals (13-15), as well as in infants (16) and adult volunteers and patients (9, 17-19). Until recently, the main limitation of this technique was that many clinicians and gastrointestinal physiologists did not have access to a mainframe computer on which the program could be run. If available, this option was often costly and awkward. Therefore, we have adapted the original FORTRAN computer program to calculate gastric emptying and gastric secretion on an IBM PC or compatible. The results provided by this program have been compared with those obtained using a PDP-10 computer (DCRT, NIH, Bethesda, Maryland). No numerical differences were observed up to the seventh decimal point, and the speed of execution is equivalent on a 286, 16-MHz PC. The size of this program is only 64 K, and it may be run from a floppy diskette. It will be provided upon request and telephone support will be available if necessary. It is expected that this new software will facilitate the diffusion of the intragastric marker dilution method and that it will foster its application to the study of various physiological and clinical questions where a precise measurement of gastric secretion and gastric emptying of liquids is required. ANDRE DUBOIS, M D , PHD
MARY MIZRAHI, MS Laboratory of Gastrointestinal and Liver Studies Digestive Diseases Division Department of Medicine Uniformed Services University of the Health Sciences Bethesda, Maryland 20814 REFERENCES 1. Rune S: The relationship between acid reduction and rate of ulcer healing. Scand J Gastroenterol Suppl 155:12-15, 1988 2. Santoro E, Morucci P, Idotta G, Scutari F: Ulcere duodenal, etude de la secretion gastrique et traitement rationnel par famotidine a doses differentes. Ann Gastroenterol Hepatol 25:211-214, 1989 3. Collen MJ, Stanczak VJ, Ciarleglio CA: Refractory duodenal ulcers (nonhealing duodenal ulcers with standard doses of antisecretory medication). Dig Dis Sci 34:233-237, 1989 4. Burget DW, Chiverton SG, Hunt RH: Is there an optimal
1303
LETTERS TO T H E EDITOR degree of acid suppression for healing of duodenal ulcers? Gastroenterology 99:345-351, 1990 5. Dubois A: Gastric emptying of liquids should not be studied independently from gastric secretion. In Functional Disorders of the Gastrointestinal Tract. W Chey (ed). New York, Raven Press, 1983, pp 151-155 6. Fortran JS, Walsh JH: Gastric acid secretion rate and buffer contents of the stomach after eating results in normal subjects and in patients with duodenal ulcer. J Clin Invest 52:645-657, 1973 7. Halter F, Keller M: A comparison between intragastric titration and gastric aspiration under basal conditions and after food or pentagastrin stimulation. Am J Dig Dis 23:723729, 1978 8. Feldman M: Comparison of acid secretion rates measured by gastric aspiration and by in vivo intragastric titration in healthy human subjects. Gastroenterology 76:954-957, 1979 9. Dubois A, Van Eerdewegh P, Gardner JD: Gastric emptying and secretion in Zollinger-Ellison syndrome. J Clin Invest 59:255-263, 1977 10. Go VLW, Hoffman AF, Summerskill WHJ: Simultaneous measurements of total pancreatic, biliary, and gastric outputs in man using a perfusion technique. Gastroenterology 58:321-328, 1970 11. Malagelada JR, Longstreth GF, Summerskill WHJ, Go VLW: Measurement of gastric functions during digestion of ordinary solid meals in man. Gastroenterology 70:203-210, 1976 12. Dubois A: Methods for studying propulsion and retropulsion of the alimentary tract contents. In Techniques in the Life Sciences. DA Titchen (ed). Amsterdam, Elsevier North Holland, 1982, p 202/1-18 13. Dubois A, Natelson BH, Van Eerdewegh P, Gardner JD: Gastric emptying and secretion in the rhesus monkey. Am J Physiol 232:EI86-E192, 1977 14. Batzri S, Harmon JW, Dubois A, Moskowitz D, Weichbrodt R, Rich NM: A new in vivo method for repeatedly studying gastric acid secretion and other secretory parameters in awake guinea pig. J Surg Res 43:398-405, 1987 15. Dorval ED, Mueller GP, Eng RR, Durakovic A, Conklin JJ, Dubois A: Effect of ionizing radiation on gastric secretion and gastric motility in monkeys. Gastroenterol 89:374-380, 1985 16. Hyman PE, Abrams C, Dubois A: Effect of metoclopramide and bethanechol on gastric emptying in infants. Pediatr Res 19:1029-1032, 1985 17. Dubois A, Castell DO: Abnormal gastric emptying response to pentagastrin in duodenal ulcer disease. Dig Dis Sci 26:292-296, 1981 18. Sasaki H, Nagulesparan M, Samloff IM, Straus E, Sievers ME, Dubois A: Low acid output in Pima Indians: A possible cause for the rarity of duodenal ulcer in this population. Dig Dis Sci 29:785-789, 1984 19. Cherner JA, Jensen RT, Dubois A, O'Dorisio TM, Gardner JD, Metcalfe DD: Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. Gastroenterology 95:657-667, 1988
1304
AUTOIMMUNE GASTRITIS: IS Helicobacter pylori A M E R E L Y C O M M E N S A L O R A PATHOGENIC AGENT? To The Editor: We h a v e read with great interest the p a p e r by O r m a n d et al (1) regarding the p r e v a l e n c e of Helicobacter pylori in s o m e specific f o r m s of chronic gastritis (ie, eosinophilic, C r o h n ' s , and M e n e t r i e r ' s gastritis). N o n e of the patients with specific f o r m s o f gastritis s h o w e d evidence o f H. pylori infection c o m p a r e d with the 71% o f the patients with chronic nonspecific gastritis. The authors concluded that the results o f the study " a d d further support to the accumulating evidence that H. pylori plays a pathogenic role in chronic nonspecific gastritis." To determine the p r e v a l e n c e of H. pylori in a further f o r m of specific chronic gastritis, we h a v e evaluated 16 patients (4 males and 12 females; m e a n age 64 years, range 5 5 - 8 0 years) with a u t o i m m u n e gastritis. All patients w e r e diagnosed as having a u t o i m m u n e gastritis on the basis of the p r e s e n c e o f p a r i e t a l cell a n t i b o d i e s , p e n t a g a s t r i n - r e s i s t a n t achlorhydria at gastric analysis, and diffuse fundal a t r o p h y by histological examination in repeated multiple biopsies; no hematological findings consistent with pernicious anemia w e r e detected. E a c h patient u n d e r w e n t u p p e r gastrointestinal endoscopy, and multiple biopsies in fundus, body, and antrum were m a d e (mean four samples, range three to five, in each region) b y separate sterile forceps. Histological specimens were stained with h e m a t o x ylin-eosin to study gastritis and with G i e m s a to search for H. pylori. Twelve patients were found to b e infected b y H. pylori. Biopsies f r o m fundus and b o d y showed the p r e s e n c e of H. pylori in both regions in all cases. The examination of the biopsies f r o m antrum detected chronic atrophic gastritis with H. pylori infection in seven cases and superficial gastritis in the remaining five patients, two of w h o m also showed H. pylori infection. In the four H. pylori-negative patients, the antral specimens revealed chronic atrophic gastritis in two and superficial gastritis in the other two patients. The results are s u m m a r i z e d in Table 1. The results of this study on H. priori infection in a u t o i m m u n e gastritis patients confirm those previously reported b y us in a smaller series (2), showing a p r e v a l e n c e of about 70%. Other authors described a lesser infection rate ranging f r o m 3 to 21% (3-6), nevertheless some others reported a p r e v a l e n c e Digestive Diseases and Sciences, Vol.37, No. 8 (August 1992)
