286
Pali
Proc. roy. Soc. Med. Volume 68 May 1975 in Peptic Ulcer
by Oliver James1 MA MRCP and J S Kenefick Mch FRCS (Departments ofMedicine and Surgery, Royal Free Hospital, London NW3)
10 Rhodes et al. (1966), in carefully conducted studies of the pH of the contents of the duodenal bulb in relation to duodenal ulcer symptoms, showed that the symptoms were present when the pH was fluctuating and low in the duodenum.
On the other hand Hurst (1911), Ryle (1926) and others have also introduced acid into the stomach but failed to reproduce the symptoms of patients with peptic ulcer. Texter et al. (1959) relieved pain in 18 of 42 subjects who were Edwards & Coghill (1968) found that pain was experiencing pain due to acute gastric ulcer by the chief symptom in 93% of 84 patients with the introduction of 200 ml of 0.1 N HC1 into gastric ulcer and in 88 % of patients with duodenal their stomachs; in a further 83 subjects with active ulcer. The pain was described as -boring, gnawing, gastric ulcer no pain was induced, but in 37 aching, nagging, cramplike, dull, sharp, hot, patients pain was produced or increased by the introduction of the acid. Texter et al. also found tearing, heaving, stretching and indescribable. marked increase in intraluminal pressure wave There appeared to be no marked difference in activity within the stomach in patients who were the character of the pain experienced in gastric experiencing ulcer pain; the increase being far or duodenal ulcer; nor was there any difference more marked in ulcers in the cardia and body of in the site of pain in the two groups. Perhaps the stomach where they were 50-70% increased, surprisingly, noctural pain occurred in 50% of than in the antrum or duodenum where the patients with duodenal ulcer and in 43 % of those increase was only about 20 % above normal. with gastric ulcer. Alkalis eased the pain over 80% of both groups of patients. Edwards & The Present Study Coghill concluded that it is not easy to distinguish The present short study has therefore been undertwo conditions which have few signs but numerous taken as a further investigation into the mechanism of pain production. As Pickering (1950) has symptoms in common. noted, one of the drawbacks to earlier experiAlthough there are many variations, the two ments in which acid was instilled into the stomach main concepts as to the cause of pain in peptic has been that the pH in the stomach varies and ulcer may be said to be championed by two thus it was not known that there was a true acid famous knights. On the one hand, Sir George stimulus to pain production at the site of the Pickering believes that, by analogy with the skin, ulcer. The fibreoptic endoscope is an ideal instruif an ulcer is bathed in strong acid then pain will ment with which to bathe peptic ulcers with acid result; on the other hand, Sir Arthur Hurst and to observe the changes in symptoms which proposed that since stretching abdominal viscera occur. In order to record the effect of the acid causes pain, then pain in peptic ulcer is caused on the ulcers, no analgesic premedication was by tension and spasm in the walls of the stomach given before the procedure. and duodenum. Patients Studied Pickering (1950) and Bonney & Pickering Eight patients with gastric ulcer were studied. All (1946) found relief of pain in subjects with duo- experienced epigastric pain as the main presenting denal ulcer and gastric ulcer following aspiration symptom, the mean duration of symptoms being of the gastric contents; returning the gastric twenty months. All had obtained some symptocontents brought back the pain. Introduction of matic relief by use of antacids. All had gastric 200-300 ml of 0.1 N HC1 into the stomach ulcer, confirmed on barium meal X-ray to be on resulted in pain which occurred after a latent the upper part of the lesser curve of the stomach. period of about 10 minutes; the pain was relieved None was neai the prepyloric region. by again removing the gastric contents. They concluded that acid acts as a chemical irritant in Procedure producing pain; but measurement of intragastric Premedication of atropine 0.6 mg was given pH at times when the subjects were pain free intramuscularly one hour before endoscopy; revealed no marked difference from the pH Xylocaine spray was applied to the pharynx just during the experiment when the subjects were before the endoscope was passed. An Olympus GIF Pan endoscope was passed into the stomach, experiencing pain. and the ulcer identified. Hydrochloric acid, 0.2 N, Present address: Royal Victoria Infirmary, was introduced via the endoscope on to the ulcer Newcastle upon Tyne, NEI 4LP Abdominal pain is the chief symptom in patients suffering from peptic ulcer whether gastric or duodenal.
'
11
Section of Surgery
at a rate of 10 ml/min for 15 minutes, the endoscope was removed and the patient remained resting for a further 15 minutes. The patients were then asked whether they had experienced any symptoms similar to their normal abdominal pain. Because of the lack of sedation the procedure proved too unpleasant for several patients who needed sedation before the endoscope was passed or during the procedure. These subjects were not included in the trial. Informed consent was obtained from all patients.
Growth of Human Tumours in Immune-suppressed Mice
Result None of the 8 patients experienced a pain in any way similar to his normal pain. The ulcer areas became a little hypernmic during the procedure but there was no other real change in appearance. Discussion It is difficult to account for the conflict between the results of this very simple experiment and those of other workers, notably Rhodes et al. One possible reason is that while the symptoms experienced in gastric ulcer and duodenal ulcer are indistinguishable the mechanism of production of symptoms may be different in the two conditions. Duodenal ulcers are intermittently bathed in acid and Rhodes' experiments suggest that when a rapid fall in pH occurs in the duodenum, pain results; perhaps prepyloric ulcers should be regarded as part of the same group as duodenal ulcers. By contrast hyperacidity is not a feature in patients with gastric ulcer in the body of the stomach. Thus it may be that in the upper part of the stomach where acidity is low and changes of intraluminal pressure are high during pain, it is these changes which are responsible for the production of the pain rather than local hyperacidity. Conversely, in the duodenum and prepyloric region changes in acidity and local hyperacidity may be responsible for the production of pain.
287
by C R Franks MB (ICRF Breast Cancer Unit, Guy's Hospital, London SEI 9RT) F T Perkins PhD FIBiOl (National Institute of Biological Standards and Control, Holly Hill, London NW3) and J Thornton Holmes FRCS (Royal Free Hospital, London NW3) In these investigations, human tumour xenograft growth has been studied. As a preliminary, three immune-deficient mouse systems were considered, using the growth of HeLa tumour implants to assess the most effective system, in which tumours from patients with primary cancer were subsequently studied. Each mouse under test was inoculated with 2 x 105 HeLa cells in a 0.2 ml inoculum, by the subcutaneous route. The 3 groups were: (1) Mice treated with antilymphocyte serum (ALS). (2) Thymectomized, irradiated, and reconstituted mice (T- B+). (3) Congenitally athymic mice (Nu Nu).
All the mice, apart from those in Group 3, were obtained from the specific pathogen free colony at the National Institute for Medical Research, in order to reduce to a minimum the complications that arose from using mice inherently infected with bacteria, viruses or helminths. Group 3 mice were obtained from the Medical Research Council Laboratory Animals Centre, Carshalton. All the mice studied were females. In Group 1, the ALS was prepared by the method of Levey & Medawar (1966). Each 100 90 20
30
0
70 1
50
F
80
90l10-5+
ALS
NuNU Nm/NU
Acknowledgments: We are grateful to Mr G Qvist for suggesting this project and for his support and encouragement.
70-
60-
so0
REFERENCES
Bonney G L W & Pickering G W (1946) Clinical Science 6, 63-90 Edwards F C & Coghill N F (1968) Quarterly Journal ofMedicine 37, 337-360 Hurst A F (1911) The Sensibility of the Alimentary Canal. Frowde and Hodder & Stoughton, London Pickering G W (1950) In: Modern Trends in Gastro-enterology. Ed. F Avery-Jones. Butterworth, London; pp 73-85 Rhodes J, Apsimon H T & Lawrie J H (1966) Gut 7, 502-508 Ryle J A (1926) Gastric Function in Health and Disease. Oxford University Press, London Texter E C, Vantrappen G R, Lazar H P, Puletti E J & Barborka C J (1959) Annals of Internal Medicine 51, 1275-1291
r403020-
10-
10
20
30
40
50 DAYS
60
70
50
90
100
Fig 1 Survival of HeLa tumours in T- B+, ALS and Nu Nu mice
Pali
Proc. roy. Soc. Med. Volume 68 May 1975 in Peptic Ulcer
by Oliver James1 MA MRCP and J S Kenefick Mch FRCS (Departments ofMedicine and Surgery, Royal Free Hospital, London NW3)
10 Rhodes et al. (1966), in carefully conducted studies of the pH of the contents of the duodenal bulb in relation to duodenal ulcer symptoms, showed that the symptoms were present when the pH was fluctuating and low in the duodenum.
On the other hand Hurst (1911), Ryle (1926) and others have also introduced acid into the stomach but failed to reproduce the symptoms of patients with peptic ulcer. Texter et al. (1959) relieved pain in 18 of 42 subjects who were Edwards & Coghill (1968) found that pain was experiencing pain due to acute gastric ulcer by the chief symptom in 93% of 84 patients with the introduction of 200 ml of 0.1 N HC1 into gastric ulcer and in 88 % of patients with duodenal their stomachs; in a further 83 subjects with active ulcer. The pain was described as -boring, gnawing, gastric ulcer no pain was induced, but in 37 aching, nagging, cramplike, dull, sharp, hot, patients pain was produced or increased by the introduction of the acid. Texter et al. also found tearing, heaving, stretching and indescribable. marked increase in intraluminal pressure wave There appeared to be no marked difference in activity within the stomach in patients who were the character of the pain experienced in gastric experiencing ulcer pain; the increase being far or duodenal ulcer; nor was there any difference more marked in ulcers in the cardia and body of in the site of pain in the two groups. Perhaps the stomach where they were 50-70% increased, surprisingly, noctural pain occurred in 50% of than in the antrum or duodenum where the patients with duodenal ulcer and in 43 % of those increase was only about 20 % above normal. with gastric ulcer. Alkalis eased the pain over 80% of both groups of patients. Edwards & The Present Study Coghill concluded that it is not easy to distinguish The present short study has therefore been undertwo conditions which have few signs but numerous taken as a further investigation into the mechanism of pain production. As Pickering (1950) has symptoms in common. noted, one of the drawbacks to earlier experiAlthough there are many variations, the two ments in which acid was instilled into the stomach main concepts as to the cause of pain in peptic has been that the pH in the stomach varies and ulcer may be said to be championed by two thus it was not known that there was a true acid famous knights. On the one hand, Sir George stimulus to pain production at the site of the Pickering believes that, by analogy with the skin, ulcer. The fibreoptic endoscope is an ideal instruif an ulcer is bathed in strong acid then pain will ment with which to bathe peptic ulcers with acid result; on the other hand, Sir Arthur Hurst and to observe the changes in symptoms which proposed that since stretching abdominal viscera occur. In order to record the effect of the acid causes pain, then pain in peptic ulcer is caused on the ulcers, no analgesic premedication was by tension and spasm in the walls of the stomach given before the procedure. and duodenum. Patients Studied Pickering (1950) and Bonney & Pickering Eight patients with gastric ulcer were studied. All (1946) found relief of pain in subjects with duo- experienced epigastric pain as the main presenting denal ulcer and gastric ulcer following aspiration symptom, the mean duration of symptoms being of the gastric contents; returning the gastric twenty months. All had obtained some symptocontents brought back the pain. Introduction of matic relief by use of antacids. All had gastric 200-300 ml of 0.1 N HC1 into the stomach ulcer, confirmed on barium meal X-ray to be on resulted in pain which occurred after a latent the upper part of the lesser curve of the stomach. period of about 10 minutes; the pain was relieved None was neai the prepyloric region. by again removing the gastric contents. They concluded that acid acts as a chemical irritant in Procedure producing pain; but measurement of intragastric Premedication of atropine 0.6 mg was given pH at times when the subjects were pain free intramuscularly one hour before endoscopy; revealed no marked difference from the pH Xylocaine spray was applied to the pharynx just during the experiment when the subjects were before the endoscope was passed. An Olympus GIF Pan endoscope was passed into the stomach, experiencing pain. and the ulcer identified. Hydrochloric acid, 0.2 N, Present address: Royal Victoria Infirmary, was introduced via the endoscope on to the ulcer Newcastle upon Tyne, NEI 4LP Abdominal pain is the chief symptom in patients suffering from peptic ulcer whether gastric or duodenal.
'
11
Section of Surgery
at a rate of 10 ml/min for 15 minutes, the endoscope was removed and the patient remained resting for a further 15 minutes. The patients were then asked whether they had experienced any symptoms similar to their normal abdominal pain. Because of the lack of sedation the procedure proved too unpleasant for several patients who needed sedation before the endoscope was passed or during the procedure. These subjects were not included in the trial. Informed consent was obtained from all patients.
Growth of Human Tumours in Immune-suppressed Mice
Result None of the 8 patients experienced a pain in any way similar to his normal pain. The ulcer areas became a little hypernmic during the procedure but there was no other real change in appearance. Discussion It is difficult to account for the conflict between the results of this very simple experiment and those of other workers, notably Rhodes et al. One possible reason is that while the symptoms experienced in gastric ulcer and duodenal ulcer are indistinguishable the mechanism of production of symptoms may be different in the two conditions. Duodenal ulcers are intermittently bathed in acid and Rhodes' experiments suggest that when a rapid fall in pH occurs in the duodenum, pain results; perhaps prepyloric ulcers should be regarded as part of the same group as duodenal ulcers. By contrast hyperacidity is not a feature in patients with gastric ulcer in the body of the stomach. Thus it may be that in the upper part of the stomach where acidity is low and changes of intraluminal pressure are high during pain, it is these changes which are responsible for the production of the pain rather than local hyperacidity. Conversely, in the duodenum and prepyloric region changes in acidity and local hyperacidity may be responsible for the production of pain.
287
by C R Franks MB (ICRF Breast Cancer Unit, Guy's Hospital, London SEI 9RT) F T Perkins PhD FIBiOl (National Institute of Biological Standards and Control, Holly Hill, London NW3) and J Thornton Holmes FRCS (Royal Free Hospital, London NW3) In these investigations, human tumour xenograft growth has been studied. As a preliminary, three immune-deficient mouse systems were considered, using the growth of HeLa tumour implants to assess the most effective system, in which tumours from patients with primary cancer were subsequently studied. Each mouse under test was inoculated with 2 x 105 HeLa cells in a 0.2 ml inoculum, by the subcutaneous route. The 3 groups were: (1) Mice treated with antilymphocyte serum (ALS). (2) Thymectomized, irradiated, and reconstituted mice (T- B+). (3) Congenitally athymic mice (Nu Nu).
All the mice, apart from those in Group 3, were obtained from the specific pathogen free colony at the National Institute for Medical Research, in order to reduce to a minimum the complications that arose from using mice inherently infected with bacteria, viruses or helminths. Group 3 mice were obtained from the Medical Research Council Laboratory Animals Centre, Carshalton. All the mice studied were females. In Group 1, the ALS was prepared by the method of Levey & Medawar (1966). Each 100 90 20
30
0
70 1
50
F
80
90l10-5+
ALS
NuNU Nm/NU
Acknowledgments: We are grateful to Mr G Qvist for suggesting this project and for his support and encouragement.
70-
60-
so0
REFERENCES
Bonney G L W & Pickering G W (1946) Clinical Science 6, 63-90 Edwards F C & Coghill N F (1968) Quarterly Journal ofMedicine 37, 337-360 Hurst A F (1911) The Sensibility of the Alimentary Canal. Frowde and Hodder & Stoughton, London Pickering G W (1950) In: Modern Trends in Gastro-enterology. Ed. F Avery-Jones. Butterworth, London; pp 73-85 Rhodes J, Apsimon H T & Lawrie J H (1966) Gut 7, 502-508 Ryle J A (1926) Gastric Function in Health and Disease. Oxford University Press, London Texter E C, Vantrappen G R, Lazar H P, Puletti E J & Barborka C J (1959) Annals of Internal Medicine 51, 1275-1291
r403020-
10-
10
20
30
40
50 DAYS
60
70
50
90
100
Fig 1 Survival of HeLa tumours in T- B+, ALS and Nu Nu mice
