Scandinavian Journal of Gastroenterology
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Parietal and Chief Cell Sensitivity to Pentagastrin Stimulation before and after Cimetidine Treatment for Duodenal Ulcer E. Aadland & A. Berstad To cite this article: E. Aadland & A. Berstad (1979) Parietal and Chief Cell Sensitivity to Pentagastrin Stimulation before and after Cimetidine Treatment for Duodenal Ulcer, Scandinavian Journal of Gastroenterology, 14:1, 111-114, DOI: 10.3109/00365527909179855 To link to this article: http://dx.doi.org/10.3109/00365527909179855
Published online: 23 Feb 2010.
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Citing articles: 4 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [UNSW Library]
Date: 15 April 2016, At: 18:59
Parietal and Chief Cell Sensitivity to Pentagastrin Stimulation before and after Cimetidine Treatment for Duodenal Ulcer E. AADLAND & A. BERSTAD Aker Hospital, Medical Dept. B. Oslo. Norway
Aadland. E. & Berstad, 4. Parietal and chief cell sensitivity to pentagastrin stimulation before and after cimetidine treatment for duodenal ulcer. Scand. J. Gastroent. 1979,14, 1 I I- 1 14.
Downloaded by [UNSW Library] at 18:59 15 April 2016
-
Gastric acid and pepsin output in response to 0.10 and 6.0 pg k g W ' of pentagastrin was studied in ten duodenal ulcer patients before and after cessation of 6 weeks of cimetidine treatment. I g/tiay. Acid output in response to the low dose of pentagastrin was on average 63% of the response to the high dose before and on average 65% after treatment. The corresponding values for pepsin output were on average 88% both before and after treatment. Thus, the parietal and chief cell sensitivity stayed unchanged after cimetidine treatment. Mean maximal acid output decreased insignificantly, from 39.4 mmol/h before to 34.9 mmol/h after cimetidine treatment. The results suggest an unchanged gastric acid and pepsin secretion capacity after short-term treatment with cimetidine for duodenal ulcer.
Key-words: Acid secretion; chief cell sensitivity; parietal cell sensitivity; pentagastrin; pepsin secretion
E. Aad/and, M.D., Medical Dept. B , Aker ffospilal, Oslo, Norway
Relapse of duodenal ulcers has been reported shortly after completing treatment with histamine H2 receptor antagonists (1 1, 15), although evidence of this was found neither in a recent review (16) nor when preliminary data from several trials were pooled (3). Some rapid and severe relapses after cessation of long-term treatment with metiamide was suggested to represent an after-effect of the drug ( 1 1). Evidence of increased gastric secretion after cimetidine treatment for duodenal ulcer (DU) has not been established in man (1, 4-6, 13). DU patients have increased sensitivity of the acidsecreting mechanism to pentagastrin stimulation (7, 9, lo), which could represent an important pathophysiological mechanism underlying the disease and the relapses. We therefore wanted to study the influence of cimetidine on this sensitivity.
MATERIALS A N D METHODS Ten patients with endoscopically verified duodenal ulcers were studied before and after cessation of 6
weeks of treatment with cimetidine, 1 g/day. In all but one patient were the ulcers endoscopically healed after the treatment period. One patient had to be treated for 8 weeks until his ulcer healed. Various degrees of duodenitis and mucosal deformity persisted in all patients. After the patients had fasted overnight, a nasogastric tube was passed and positioned under fluoroscopic control. The stomach was emptied, and the gastric juice collected in nine 15-min portions and analysed for acid and pepsin concentrations (2). After collection of basal secretion for 30 min, pentagastrin, 0.10 or 6.0 pg . kg-lh-l, was infused in isotonic saline for 105 min at a constant rate of 22 ml/h. Both before and after cessation of cimetidine treatment the secretion tests were carried out on 2 consecutive days in random order. The second series of tests was performed 60 and 84 h after the last dose of cimetidine, when no cimetidine is supposed to be left in the body (14). Acid and pepsin output during the last hour of each test was taken to represent the response t o the
E. Aadland di A. Berstad
112
dose of pentagastrin , yglkg-h 0.10
6.0
60
/
50
H+
before
output
40
mmol/h
30
20
after
Downloaded by [UNSW Library] at 18:59 15 April 2016
6 weeks of daily cimetidine treatment
10
Fig. 1. Basal acid output in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean and individual values.
0 before after
before after
6 weeks of daily cimetidine treatment
applied dose of pentagastrin. Parietal and chief cell Fig. 3. Gastric acid output in 10 duodenal ulcer patients, sensitivity was calculated as the output of acid and in response to 0.10 and 6.0 pg/kg/h of pentagastrin before pepsin in response to 0.10 Fg . kg-lh-' of pentagas- and after 6 weeks of cimetidine treatment. Mean and trin in percentage of the corresponding response to individual values. 6.0 pg . kg-lh-' of pentagastrin. Statistical differences were evaluated by the Wildose of p e n t a g a s t r i n p g / k p - h coxon ranked pairs test. P values < 0.05 were rea1o 6.0 garded as significant. 300 120 Pepsin
100
output
basal pepsin
80
rng/h
output
60
me/
100
h 40
20 0 before after
0 before
after
6 weeks of daily cirnetidine treatment
Fig. 2. Basal pepsin output in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean .and individual values.
before after
6 weeks of daily cimetidine t r e a t m e n t
Fig. 4. Pepsin output in 10 duodenal ulcer patients, in response to 0.10 and 6.0 pg/kg/h of pentagastrin, before and after 6 weeks of cimetidine treatment. Mean and individual values.
Parietal and Chief Cell Sensitivity after Cimetidine
Downloaded by [UNSW Library] at 18:59 15 April 2016
RESULTS
Chiafcell sensitivity
After the end of cimetidine treatment no significant change was found in mean basal acid (Fig. 1) and. pepsin (Fig. 2) output. In two patients (V and X) basal acid and pepsin output increased markedly after cimetidine .treatment. In one of these patients (V) the low dose of pentagastrin then elicited maximal acid output. Mean gastric acid output in response to pentagastrin, 0.10 and 6.0 pg . kg-'h-', was 24.5 and 39.4mmol/h before compared to 23.5 and 34.9 mmol/h after cessation of cimetidine treatment, respectively (Fig. 3). The values are not statistically different. The corresponding values for pepsin output were 143.6 and 160.3 mg/h before compared to 124.3 and 140.6 mg/h after treatment (Fig. 4). The difference was not significant. Maximal acid output increased in three subjects, but in two of these only marginally. Marked increase in individual maximal pepsin output was not found. The estimated mean sensitivity of the parietal (Fig. 5) and chief cells (Fig. 6) to pentagastrin stimulation was not significantly different before and after cessation of treatment with cimetidine. Before treatment the low dose of pentagastrin gave on average 63% of maximal acid response and after treatment on average 65%. The corresponding values for pepsin output was on average 88% both
/
1
H'wtput in response to
a8
80
-
60
-
of pentauastrin do
-
in response to O.lOpu/ho-h as O/o of response to
6.0 rr@/ho- h
*O0
1
before
after
6 weeks of daily cimetidine treatment
Fig. 6. Chief cell sensitivity in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean and individual values.
before and after treatment. It may be noteworthy that the scatter of individual results of basal and stimulated acid output and of parietal cell sensitivity was greater after than before treatment. In two patients (V and IX) the low dose of pentagastrin after treatment evoked maximal acid secretion, which caused a marked increase in estimated parietal cell sensitivity in these subjects.
A high sensitivity of the parietal cells to pentagastrin stimulation has been demonstrated in DU patients (7, 9, lo). Roland (10) calculated that D U patients required on average 0.04 pg kg-'h-' of pentagastrin for half maximal stimulation of gastric acid secretion compared to 0.11 pg . kg-'h-' in healthy subjects. The difference was significant. Maximal acid output in the two groups was not significantly different. The study demonstrated that a high sensitivity, to pentagastrin stimulation was a more characteristic feature of DU patients than a high maximal acid output when compared to healthy young subjects. The present study was carried out by the same technique as that of Roland (10). Acid output in response to 0.10 pg . kg-'h-' of pentagastrin in percentage of the response to 6.0 pg . kg-lh-', which evokes maximal acid secretion (S), was on average +
0.10 p0Ikg-h
% of
response t o
1-
DISCUSSION
Parietal cell sensitivity
lW
4
120 100
Papsinoutput
60.
6.0 pg/kg-h of pentawstrin
I.
2ol
113
0
before
after
6 weeks of daily cimetidine treatment
Fig. 5. Parietal cell sensitivity in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean and individual values.
Downloaded by [UNSW Library] at 18:59 15 April 2016
114
E . Aadland & A . Berstad
63% before and 65% after cessation of 6 weeks of cimetidine treatment. Since the low dose of pentagastrin evoked on average more than 50% of maximal acid output, our results are consistent with a high parietal cell sensitivity to pentagastrin stimulation. The ten patients studied had active duodenal ulcers at admittance and a healed ulcer with relief of symptoms at the end of treatment. The high parietal cell sensitivity found in our patients also after the treatment period, when the ulcers were healed, suggest that the sensitivity is independent of manifest ulcers. A decreased sensitivity due to healing of the ulcers could, however, theoretically mask an increased sensitivity due to cimetidine. Mean basal acid output was not significantly different before and after treatment with cimetidine. Marked differences in individual basal acid outputs was noticed. Mean maximal acid output (pentagastrin, 6.0 pg . kg-lh-l) decreased insignificantly from 39.4 mmol/h before to 34.9 mmol/h after the treatment period. Thus no significant difference of acidsecretory capacity in response to pentagastrin is observed after treatment with cimetidine (1, 4-6) except in one study (12), in which low blood concentrations of cimetidine were measured. Our recent study (1) showed that stimulated (pentagastrin 1.5 pg . kg-lh-') gastric acid output stayed unchanged after a cimetidine treatment period of 6 weeks. Accordingly, no significant change of basal acid output or acid output in response to O.lCk1.56.0 pg . kg-lh-' of pentagastrin seems to occur after finishing 6 weeks of cimetidine treatment, 1 g/day, suggesting an unchanged acid dose-response curve to pentagastrin. The greater scatter of individual basal and stimulated gastric acid output as well as of individual parietal cell sensitivity after the cimetidine treatment period than before may suggest individual differences. However, patient V (a female) was the only one in whom both basal acid output and parietal cell sensitivity increased markedly after the treatment. Her ulcer relapsed after 5 months of maintenance treatment with placebo. She was subsequently operated on with proximal gastric vagotomy. In our patients no ulcer relapse shortly after cessation of cimetidine treatment was observed. Both basal and stimulated mean pepsin output and mean chiefcell sensitivity to pentagastrin stimu-
lation were not significantly changed after the cimetidine treatment period. The inhibition of pepsin by histamine H, receptor antagonists is less pronounced than that of acid (2), and the kinetics of cimetidine-induced inhibition of acid and pepsin secretion seems to differ (2). In conclusion, cimetidine seems not to affect the sensitivity of the acid and pepsin-producing cells of DU patients to pentagastrin stimulation. The high parietal cell sensitivity found in most of the patients is maintained after cessation of cimetidine treatment. In this way the parietal cell sensitivity may have a bearing on the liability of the ulcers to relapse after treatment (4). A high sensitivity to humoral stimuli may reflect a disposition for DU disease, independent of whether the ulcer is active or inactive, and this disposition is not changed by a course of cimetidine treatment. REFERENCES 1. Aadland, E. & Berstad, A. Scand. J. Gastroent. 1978, 13, 193-197 2. Aadland, E., Berstad, A. & Semb, L. S. Scand. J . Gastroeni. 1977, 12, 501-506 3. Bardhan, K. D., Blum, A. & Gillespie, G. Lancet 1977, 1, 900-901 4. Bodemar, G. & Walan, A. Lancet 1 9 7 8 , l . 403-407 5. Domschke, W., Domschke, S. & Demling, L. pp. 2 17-223 in Cimetidine. Proceedings of the Second International Symposium on Histamine H,-Receptor Antagonists. Excerpta Medica, 1977 6. Hetzel, D. J., Hansky, J., Shearman, D. J. C., Korman, M. G., Hecker, R., Taggart, G . J., Jackson, R. & Gabb, B. W. Gastroenierology 1978, 7 4 (Suppl.), 389-392 7. Isenberg, J. I., Grossman, M. I., Maxwell, V. & Walsh, J. H. J. Clin. Invest. 1975, 55, 330-337 8. Johnston, D. & Jepson, K. Lancet 1967,2,585-588 9. Petersen, H. & Myren, J. Scand. J. Gastroent. 1975, 10, 705-714 10. Roland, M. Scand. J. Gastroent. 1975,10,603-608 I I . Saunders, J. H. & Wormsley, K. G. Lancet 1977, I , 765-76 7 12. Sewing, K. F., Hagie, L.. Ippoliti, A. F., Isenberg, J. I.. Samloff, I. M. & Sturdevant, R. A. L. GasiroenterolOD 1978. 74 (SUPPI.), 376-379 13. Spence, R. W., Celestin, L. R. & McCormick. D. A. pp. 101-107 in Cimeiidine. Proceedings of ihe Second International Symposium on Histamine Hz Receptor Antagonists. Excerpta Medica, 1977 14. Walkenstein, S. S.. Dubb. J. W., Randolph, W. C., Westlake, W. J., Stote, R. M. & Intoccia, A. P. Gastroenterology 1978. 7 4 (Suppl.), 360-365 15. Wallace, W. A., Orr, C. M. & Beam, A, R., Brit. Med. J. 1977, 2, 865-866 16. Winship, D. H. Gastroenterology 1978, 7 4 (Suppl.), 402-406. Received 5 May 1978 Accepted 8 September 1978
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Parietal and Chief Cell Sensitivity to Pentagastrin Stimulation before and after Cimetidine Treatment for Duodenal Ulcer E. Aadland & A. Berstad To cite this article: E. Aadland & A. Berstad (1979) Parietal and Chief Cell Sensitivity to Pentagastrin Stimulation before and after Cimetidine Treatment for Duodenal Ulcer, Scandinavian Journal of Gastroenterology, 14:1, 111-114, DOI: 10.3109/00365527909179855 To link to this article: http://dx.doi.org/10.3109/00365527909179855
Published online: 23 Feb 2010.
Submit your article to this journal
Article views: 4
View related articles
Citing articles: 4 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [UNSW Library]
Date: 15 April 2016, At: 18:59
Parietal and Chief Cell Sensitivity to Pentagastrin Stimulation before and after Cimetidine Treatment for Duodenal Ulcer E. AADLAND & A. BERSTAD Aker Hospital, Medical Dept. B. Oslo. Norway
Aadland. E. & Berstad, 4. Parietal and chief cell sensitivity to pentagastrin stimulation before and after cimetidine treatment for duodenal ulcer. Scand. J. Gastroent. 1979,14, 1 I I- 1 14.
Downloaded by [UNSW Library] at 18:59 15 April 2016
-
Gastric acid and pepsin output in response to 0.10 and 6.0 pg k g W ' of pentagastrin was studied in ten duodenal ulcer patients before and after cessation of 6 weeks of cimetidine treatment. I g/tiay. Acid output in response to the low dose of pentagastrin was on average 63% of the response to the high dose before and on average 65% after treatment. The corresponding values for pepsin output were on average 88% both before and after treatment. Thus, the parietal and chief cell sensitivity stayed unchanged after cimetidine treatment. Mean maximal acid output decreased insignificantly, from 39.4 mmol/h before to 34.9 mmol/h after cimetidine treatment. The results suggest an unchanged gastric acid and pepsin secretion capacity after short-term treatment with cimetidine for duodenal ulcer.
Key-words: Acid secretion; chief cell sensitivity; parietal cell sensitivity; pentagastrin; pepsin secretion
E. Aad/and, M.D., Medical Dept. B , Aker ffospilal, Oslo, Norway
Relapse of duodenal ulcers has been reported shortly after completing treatment with histamine H2 receptor antagonists (1 1, 15), although evidence of this was found neither in a recent review (16) nor when preliminary data from several trials were pooled (3). Some rapid and severe relapses after cessation of long-term treatment with metiamide was suggested to represent an after-effect of the drug ( 1 1). Evidence of increased gastric secretion after cimetidine treatment for duodenal ulcer (DU) has not been established in man (1, 4-6, 13). DU patients have increased sensitivity of the acidsecreting mechanism to pentagastrin stimulation (7, 9, lo), which could represent an important pathophysiological mechanism underlying the disease and the relapses. We therefore wanted to study the influence of cimetidine on this sensitivity.
MATERIALS A N D METHODS Ten patients with endoscopically verified duodenal ulcers were studied before and after cessation of 6
weeks of treatment with cimetidine, 1 g/day. In all but one patient were the ulcers endoscopically healed after the treatment period. One patient had to be treated for 8 weeks until his ulcer healed. Various degrees of duodenitis and mucosal deformity persisted in all patients. After the patients had fasted overnight, a nasogastric tube was passed and positioned under fluoroscopic control. The stomach was emptied, and the gastric juice collected in nine 15-min portions and analysed for acid and pepsin concentrations (2). After collection of basal secretion for 30 min, pentagastrin, 0.10 or 6.0 pg . kg-lh-l, was infused in isotonic saline for 105 min at a constant rate of 22 ml/h. Both before and after cessation of cimetidine treatment the secretion tests were carried out on 2 consecutive days in random order. The second series of tests was performed 60 and 84 h after the last dose of cimetidine, when no cimetidine is supposed to be left in the body (14). Acid and pepsin output during the last hour of each test was taken to represent the response t o the
E. Aadland di A. Berstad
112
dose of pentagastrin , yglkg-h 0.10
6.0
60
/
50
H+
before
output
40
mmol/h
30
20
after
Downloaded by [UNSW Library] at 18:59 15 April 2016
6 weeks of daily cimetidine treatment
10
Fig. 1. Basal acid output in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean and individual values.
0 before after
before after
6 weeks of daily cimetidine treatment
applied dose of pentagastrin. Parietal and chief cell Fig. 3. Gastric acid output in 10 duodenal ulcer patients, sensitivity was calculated as the output of acid and in response to 0.10 and 6.0 pg/kg/h of pentagastrin before pepsin in response to 0.10 Fg . kg-lh-' of pentagas- and after 6 weeks of cimetidine treatment. Mean and trin in percentage of the corresponding response to individual values. 6.0 pg . kg-lh-' of pentagastrin. Statistical differences were evaluated by the Wildose of p e n t a g a s t r i n p g / k p - h coxon ranked pairs test. P values < 0.05 were rea1o 6.0 garded as significant. 300 120 Pepsin
100
output
basal pepsin
80
rng/h
output
60
me/
100
h 40
20 0 before after
0 before
after
6 weeks of daily cirnetidine treatment
Fig. 2. Basal pepsin output in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean .and individual values.
before after
6 weeks of daily cimetidine t r e a t m e n t
Fig. 4. Pepsin output in 10 duodenal ulcer patients, in response to 0.10 and 6.0 pg/kg/h of pentagastrin, before and after 6 weeks of cimetidine treatment. Mean and individual values.
Parietal and Chief Cell Sensitivity after Cimetidine
Downloaded by [UNSW Library] at 18:59 15 April 2016
RESULTS
Chiafcell sensitivity
After the end of cimetidine treatment no significant change was found in mean basal acid (Fig. 1) and. pepsin (Fig. 2) output. In two patients (V and X) basal acid and pepsin output increased markedly after cimetidine .treatment. In one of these patients (V) the low dose of pentagastrin then elicited maximal acid output. Mean gastric acid output in response to pentagastrin, 0.10 and 6.0 pg . kg-'h-', was 24.5 and 39.4mmol/h before compared to 23.5 and 34.9 mmol/h after cessation of cimetidine treatment, respectively (Fig. 3). The values are not statistically different. The corresponding values for pepsin output were 143.6 and 160.3 mg/h before compared to 124.3 and 140.6 mg/h after treatment (Fig. 4). The difference was not significant. Maximal acid output increased in three subjects, but in two of these only marginally. Marked increase in individual maximal pepsin output was not found. The estimated mean sensitivity of the parietal (Fig. 5) and chief cells (Fig. 6) to pentagastrin stimulation was not significantly different before and after cessation of treatment with cimetidine. Before treatment the low dose of pentagastrin gave on average 63% of maximal acid response and after treatment on average 65%. The corresponding values for pepsin output was on average 88% both
/
1
H'wtput in response to
a8
80
-
60
-
of pentauastrin do
-
in response to O.lOpu/ho-h as O/o of response to
6.0 rr@/ho- h
*O0
1
before
after
6 weeks of daily cimetidine treatment
Fig. 6. Chief cell sensitivity in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean and individual values.
before and after treatment. It may be noteworthy that the scatter of individual results of basal and stimulated acid output and of parietal cell sensitivity was greater after than before treatment. In two patients (V and IX) the low dose of pentagastrin after treatment evoked maximal acid secretion, which caused a marked increase in estimated parietal cell sensitivity in these subjects.
A high sensitivity of the parietal cells to pentagastrin stimulation has been demonstrated in DU patients (7, 9, lo). Roland (10) calculated that D U patients required on average 0.04 pg kg-'h-' of pentagastrin for half maximal stimulation of gastric acid secretion compared to 0.11 pg . kg-'h-' in healthy subjects. The difference was significant. Maximal acid output in the two groups was not significantly different. The study demonstrated that a high sensitivity, to pentagastrin stimulation was a more characteristic feature of DU patients than a high maximal acid output when compared to healthy young subjects. The present study was carried out by the same technique as that of Roland (10). Acid output in response to 0.10 pg . kg-'h-' of pentagastrin in percentage of the response to 6.0 pg . kg-lh-', which evokes maximal acid secretion (S), was on average +
0.10 p0Ikg-h
% of
response t o
1-
DISCUSSION
Parietal cell sensitivity
lW
4
120 100
Papsinoutput
60.
6.0 pg/kg-h of pentawstrin
I.
2ol
113
0
before
after
6 weeks of daily cimetidine treatment
Fig. 5. Parietal cell sensitivity in 10 duodenal ulcer patients before and after 6 weeks of cimetidine treatment. Mean and individual values.
Downloaded by [UNSW Library] at 18:59 15 April 2016
114
E . Aadland & A . Berstad
63% before and 65% after cessation of 6 weeks of cimetidine treatment. Since the low dose of pentagastrin evoked on average more than 50% of maximal acid output, our results are consistent with a high parietal cell sensitivity to pentagastrin stimulation. The ten patients studied had active duodenal ulcers at admittance and a healed ulcer with relief of symptoms at the end of treatment. The high parietal cell sensitivity found in our patients also after the treatment period, when the ulcers were healed, suggest that the sensitivity is independent of manifest ulcers. A decreased sensitivity due to healing of the ulcers could, however, theoretically mask an increased sensitivity due to cimetidine. Mean basal acid output was not significantly different before and after treatment with cimetidine. Marked differences in individual basal acid outputs was noticed. Mean maximal acid output (pentagastrin, 6.0 pg . kg-lh-l) decreased insignificantly from 39.4 mmol/h before to 34.9 mmol/h after the treatment period. Thus no significant difference of acidsecretory capacity in response to pentagastrin is observed after treatment with cimetidine (1, 4-6) except in one study (12), in which low blood concentrations of cimetidine were measured. Our recent study (1) showed that stimulated (pentagastrin 1.5 pg . kg-lh-') gastric acid output stayed unchanged after a cimetidine treatment period of 6 weeks. Accordingly, no significant change of basal acid output or acid output in response to O.lCk1.56.0 pg . kg-lh-' of pentagastrin seems to occur after finishing 6 weeks of cimetidine treatment, 1 g/day, suggesting an unchanged acid dose-response curve to pentagastrin. The greater scatter of individual basal and stimulated gastric acid output as well as of individual parietal cell sensitivity after the cimetidine treatment period than before may suggest individual differences. However, patient V (a female) was the only one in whom both basal acid output and parietal cell sensitivity increased markedly after the treatment. Her ulcer relapsed after 5 months of maintenance treatment with placebo. She was subsequently operated on with proximal gastric vagotomy. In our patients no ulcer relapse shortly after cessation of cimetidine treatment was observed. Both basal and stimulated mean pepsin output and mean chiefcell sensitivity to pentagastrin stimu-
lation were not significantly changed after the cimetidine treatment period. The inhibition of pepsin by histamine H, receptor antagonists is less pronounced than that of acid (2), and the kinetics of cimetidine-induced inhibition of acid and pepsin secretion seems to differ (2). In conclusion, cimetidine seems not to affect the sensitivity of the acid and pepsin-producing cells of DU patients to pentagastrin stimulation. The high parietal cell sensitivity found in most of the patients is maintained after cessation of cimetidine treatment. In this way the parietal cell sensitivity may have a bearing on the liability of the ulcers to relapse after treatment (4). A high sensitivity to humoral stimuli may reflect a disposition for DU disease, independent of whether the ulcer is active or inactive, and this disposition is not changed by a course of cimetidine treatment. REFERENCES 1. Aadland, E. & Berstad, A. Scand. J. Gastroent. 1978, 13, 193-197 2. Aadland, E., Berstad, A. & Semb, L. S. Scand. J . Gastroeni. 1977, 12, 501-506 3. Bardhan, K. D., Blum, A. & Gillespie, G. Lancet 1977, 1, 900-901 4. Bodemar, G. & Walan, A. Lancet 1 9 7 8 , l . 403-407 5. Domschke, W., Domschke, S. & Demling, L. pp. 2 17-223 in Cimetidine. Proceedings of the Second International Symposium on Histamine H,-Receptor Antagonists. Excerpta Medica, 1977 6. Hetzel, D. J., Hansky, J., Shearman, D. J. C., Korman, M. G., Hecker, R., Taggart, G . J., Jackson, R. & Gabb, B. W. Gastroenierology 1978, 7 4 (Suppl.), 389-392 7. Isenberg, J. I., Grossman, M. I., Maxwell, V. & Walsh, J. H. J. Clin. Invest. 1975, 55, 330-337 8. Johnston, D. & Jepson, K. Lancet 1967,2,585-588 9. Petersen, H. & Myren, J. Scand. J. Gastroent. 1975, 10, 705-714 10. Roland, M. Scand. J. Gastroent. 1975,10,603-608 I I . Saunders, J. H. & Wormsley, K. G. Lancet 1977, I , 765-76 7 12. Sewing, K. F., Hagie, L.. Ippoliti, A. F., Isenberg, J. I.. Samloff, I. M. & Sturdevant, R. A. L. GasiroenterolOD 1978. 74 (SUPPI.), 376-379 13. Spence, R. W., Celestin, L. R. & McCormick. D. A. pp. 101-107 in Cimeiidine. Proceedings of ihe Second International Symposium on Histamine Hz Receptor Antagonists. Excerpta Medica, 1977 14. Walkenstein, S. S.. Dubb. J. W., Randolph, W. C., Westlake, W. J., Stote, R. M. & Intoccia, A. P. Gastroenterology 1978. 7 4 (Suppl.), 360-365 15. Wallace, W. A., Orr, C. M. & Beam, A, R., Brit. Med. J. 1977, 2, 865-866 16. Winship, D. H. Gastroenterology 1978, 7 4 (Suppl.), 402-406. Received 5 May 1978 Accepted 8 September 1978
