73
Letters to the Editor CHEMICAL FACTORS IN ÆTIOLOGY OF DUODENAL ULCER
chemicals. Only whether chemicals ulcer in man.
epidemiological studies can indicate related to the xtiology of duodenal
are
Department of Pathology, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Massachusetts 02115, U.S.A.
SANDOR SZABO EDWARD S. REYNOLDS MARY TREINEN MOSLEN.
SIR Your editorial (May 10, p. 1074) prompts us to a public plea for epidemiological inquiry into the relationship between exposure and/or consumption of make
chemicals and the incidence of duodenal ulcer.
Many compounds widely used in industry, agriculture, and medicine produce duodenal ulcer in laboratory animals. a Propionitrile (ethyl cyanide, CH3.CH2.CN) induces solitary perforating duodenal ulcer in the rat.1 Cysteamine, 1-4 3,4-toluenediamine5 and 3,4-toluenedithiol6 also found to have a similar action. When the initial reports appeared, similarities in structure or pharmacological properties of the compounds were not recognised. The ability of drugs to produce duodenal ulcer in the rat now seems to be related to an ethane backbone (2-carbon moiety) bearing cyano, sulphydryl, amino, or chloro groups on one or both ends of the chain.6,7 Branching of the chain or insertion of a hydroxyl diminishes ulcerogenesis.’ Unsaturated homologues, such as acrylonitrile 8,9 (vinyl cyanide, CH2.CH.CN) and numerous allyl compounds, have adrenocortiolytic activity.6,7,10 To date, we have identified 26 chemicals (e.g., butyronitrile, ethylamine, allyl mercaptan, homologues of pyridimine and toluidine) which produce duodenal ulcer, and 30 compounds which induce adrenocortical necrosis in the rat.6,7,10 Many of the chemicals affect both the duodenum and the adrenal gland. Some of these results were presented at a conference on public-health implications of components of plastics manufacture, organised by the National Institutes of Hea Ith.10 We wonder whether those who manufacture or use such chemicals might have a higher incidence of peptic-ulcer disease than the rest of the population. Only the relationship between aspirin and peptic ulcer is generally accepted in man.11 Could the geographical distribution of gastroduodenal ulcer disease be related to the presence of other chemicals in the environment (e.g., as pollutants) ? Propionitrile is an industrial intermediate and solvent. Propionic acid and other propionates are widely used as mould inhibitors of grain, and fungicides in general, and have been noted to stimulate appetite in swine. Propionitrileinduced duodenal ulcers are also associated with enhanced gastric secretion 12 and are prevented by antacids and antisecretory agents.13 Cysteamine is given for radiation sickness and as an antidote for acetaminophen (paracetamol) poisoning. Butyronitrile is used in poultry. Allyl mercaptan is a common flavouring agent (garlic). Are these chemicals natural or artificial constituents of our food ? We hope that the association of hepatic angiosarcoma with occupational exposure to vinyl chloride has heightened awareness of the potential hazards of synthetic were
1. 2. 3.
4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
Szabo, S., Selye, H. Archs Path. 1972, 93, 389. Selye, H., Szabo, S. Nature, 1973, 244, 458. Groves, W. G., Schlosser, J. H., Mead, F. D. Res. Comm. chem. Path. Pharmac. 1974, 9, 523. Robert, A., Nezamis, J. E., Lancaster, C., Badalamenti, J. N. Digestion, 1974, 11, 199. Selye, H. Proc. Soc. exp. Biol. Med. 1973, 142, 1192. Szabo, S. Proc. Vth Wld Congr. Gastroenterol. 1974, p. 169. Szabo, S., Feldman, D., Reynolds, E. S. Fedn Proc. 1975, 34, 227. Szabo, S., Selye, H. Endokrinologie, 1971, 57, 405. Szabo, S., Selye, H. Endocr. exp. 1972, 6, 141. Szabo, S., Reynolds, E. S. Environ. Hlth Persp. (in the press). Grossman, M. I. in Textbook of Medicine (edited by P. B. Beeson). Philadelphia, 1975. Szabo, S., Dzau, V. J., Feldman, D., Reynolds, E. S. Clin. Res. 1974, 22, 370A. Robert, A., Nezamis, J. E., Lancaster, C. Toxicol. appl. Pharmac. 1975, 31, 201.
THE TEACHING OF ANATOMY
SIR,-As an anatomist who has advocated a much greater involvement of radiology in the teaching of anatomy,1 I was most disappointed to read Dr Bull’s criticism (June 7, p. 1290). His accusation is far too generalised and he is not familiar with the situation in some provincial medical schools. In Manchester the radiologists make a valuable and very popular contribution to a course in applied anatomy for the second-year students. Moreover, Dr Bull is less than fair to Professor Coupland (May 3, p. 1028). At the Nottingham Medical School a very determined effort has been made to involve radiologists in the teaching of the basic medical sciences and especially to forge close ties with the department of human morphology. In fact, it was proposed that the recently established readership in radiology should be attached to the department of human morphology.
Traditionally, anatomy departments have relied heavily teaching of topographical anatomy on demonstrators preparing for a career in surgery. For them, dissecting for the
the cadaver is still considered a very effective way of learning anatomy. It is almost inevitable that the demonstrators, who have " front-line " contact with students, will tend to emphasise cadaveric anatomy. It does not help the present situation to compare the expertise of the radiologist with that of the anatomist. The knowledge of both groups should be complementary in the teaching of medical students. Moreover, Dr Bull’s implied " take-over " bid is completely impracticable. Radiologists are far. too busy with clinical work to engage in a heavy teaching The impending establishment of more programme. academic departments of radiology surely points the way towards very fruitful cooperation between anatomists and radiologists. Now that the Royal College of Radiologists has been established it would be of enormous value if the College would, as part of their training, make it mandatory for trainee radiologists to spend part of their time teaching in anatomy departments as demonstrators, just as primary In this way F.R.C.S. candidates have for so many years. emphasis on cadaveric anatomy would diminish whilst the anatomy of the living subject would receive much greater emphasis. Also it would be helpful if joint permanent appointments could be established between anatomy and radiology departments. This might attract more medical graduates into anatomy departments and career anatomists trained in the essentials of radiology might, by assisting in the more routine investigations, spare the expert radiologist for the highly specialised techniques. In the field of research, especially with the advent of the various scanning techniques, students reading for an intercalated B.SC. could be involved in radiological projects. After qualifying, such students could fortify the staffing of radiology and anatomy departments, particularly if they held joint appointments.
Finally, the reason a student may not know the position of the spleen (which will surely have been taught) is that anatomy teaching time has been so curtailed (to be replaced by more fashionable subjects) and the general congestion of the whole curriculum is so great that the student has 1. Br. med.
J. 1968, ii,
48.
Letters to the Editor CHEMICAL FACTORS IN ÆTIOLOGY OF DUODENAL ULCER
chemicals. Only whether chemicals ulcer in man.
epidemiological studies can indicate related to the xtiology of duodenal
are
Department of Pathology, Peter Bent Brigham Hospital, Harvard Medical School, Boston, Massachusetts 02115, U.S.A.
SANDOR SZABO EDWARD S. REYNOLDS MARY TREINEN MOSLEN.
SIR Your editorial (May 10, p. 1074) prompts us to a public plea for epidemiological inquiry into the relationship between exposure and/or consumption of make
chemicals and the incidence of duodenal ulcer.
Many compounds widely used in industry, agriculture, and medicine produce duodenal ulcer in laboratory animals. a Propionitrile (ethyl cyanide, CH3.CH2.CN) induces solitary perforating duodenal ulcer in the rat.1 Cysteamine, 1-4 3,4-toluenediamine5 and 3,4-toluenedithiol6 also found to have a similar action. When the initial reports appeared, similarities in structure or pharmacological properties of the compounds were not recognised. The ability of drugs to produce duodenal ulcer in the rat now seems to be related to an ethane backbone (2-carbon moiety) bearing cyano, sulphydryl, amino, or chloro groups on one or both ends of the chain.6,7 Branching of the chain or insertion of a hydroxyl diminishes ulcerogenesis.’ Unsaturated homologues, such as acrylonitrile 8,9 (vinyl cyanide, CH2.CH.CN) and numerous allyl compounds, have adrenocortiolytic activity.6,7,10 To date, we have identified 26 chemicals (e.g., butyronitrile, ethylamine, allyl mercaptan, homologues of pyridimine and toluidine) which produce duodenal ulcer, and 30 compounds which induce adrenocortical necrosis in the rat.6,7,10 Many of the chemicals affect both the duodenum and the adrenal gland. Some of these results were presented at a conference on public-health implications of components of plastics manufacture, organised by the National Institutes of Hea Ith.10 We wonder whether those who manufacture or use such chemicals might have a higher incidence of peptic-ulcer disease than the rest of the population. Only the relationship between aspirin and peptic ulcer is generally accepted in man.11 Could the geographical distribution of gastroduodenal ulcer disease be related to the presence of other chemicals in the environment (e.g., as pollutants) ? Propionitrile is an industrial intermediate and solvent. Propionic acid and other propionates are widely used as mould inhibitors of grain, and fungicides in general, and have been noted to stimulate appetite in swine. Propionitrileinduced duodenal ulcers are also associated with enhanced gastric secretion 12 and are prevented by antacids and antisecretory agents.13 Cysteamine is given for radiation sickness and as an antidote for acetaminophen (paracetamol) poisoning. Butyronitrile is used in poultry. Allyl mercaptan is a common flavouring agent (garlic). Are these chemicals natural or artificial constituents of our food ? We hope that the association of hepatic angiosarcoma with occupational exposure to vinyl chloride has heightened awareness of the potential hazards of synthetic were
1. 2. 3.
4. 5. 6. 7. 8. 9. 10. 11. 12. 13.
Szabo, S., Selye, H. Archs Path. 1972, 93, 389. Selye, H., Szabo, S. Nature, 1973, 244, 458. Groves, W. G., Schlosser, J. H., Mead, F. D. Res. Comm. chem. Path. Pharmac. 1974, 9, 523. Robert, A., Nezamis, J. E., Lancaster, C., Badalamenti, J. N. Digestion, 1974, 11, 199. Selye, H. Proc. Soc. exp. Biol. Med. 1973, 142, 1192. Szabo, S. Proc. Vth Wld Congr. Gastroenterol. 1974, p. 169. Szabo, S., Feldman, D., Reynolds, E. S. Fedn Proc. 1975, 34, 227. Szabo, S., Selye, H. Endokrinologie, 1971, 57, 405. Szabo, S., Selye, H. Endocr. exp. 1972, 6, 141. Szabo, S., Reynolds, E. S. Environ. Hlth Persp. (in the press). Grossman, M. I. in Textbook of Medicine (edited by P. B. Beeson). Philadelphia, 1975. Szabo, S., Dzau, V. J., Feldman, D., Reynolds, E. S. Clin. Res. 1974, 22, 370A. Robert, A., Nezamis, J. E., Lancaster, C. Toxicol. appl. Pharmac. 1975, 31, 201.
THE TEACHING OF ANATOMY
SIR,-As an anatomist who has advocated a much greater involvement of radiology in the teaching of anatomy,1 I was most disappointed to read Dr Bull’s criticism (June 7, p. 1290). His accusation is far too generalised and he is not familiar with the situation in some provincial medical schools. In Manchester the radiologists make a valuable and very popular contribution to a course in applied anatomy for the second-year students. Moreover, Dr Bull is less than fair to Professor Coupland (May 3, p. 1028). At the Nottingham Medical School a very determined effort has been made to involve radiologists in the teaching of the basic medical sciences and especially to forge close ties with the department of human morphology. In fact, it was proposed that the recently established readership in radiology should be attached to the department of human morphology.
Traditionally, anatomy departments have relied heavily teaching of topographical anatomy on demonstrators preparing for a career in surgery. For them, dissecting for the
the cadaver is still considered a very effective way of learning anatomy. It is almost inevitable that the demonstrators, who have " front-line " contact with students, will tend to emphasise cadaveric anatomy. It does not help the present situation to compare the expertise of the radiologist with that of the anatomist. The knowledge of both groups should be complementary in the teaching of medical students. Moreover, Dr Bull’s implied " take-over " bid is completely impracticable. Radiologists are far. too busy with clinical work to engage in a heavy teaching The impending establishment of more programme. academic departments of radiology surely points the way towards very fruitful cooperation between anatomists and radiologists. Now that the Royal College of Radiologists has been established it would be of enormous value if the College would, as part of their training, make it mandatory for trainee radiologists to spend part of their time teaching in anatomy departments as demonstrators, just as primary In this way F.R.C.S. candidates have for so many years. emphasis on cadaveric anatomy would diminish whilst the anatomy of the living subject would receive much greater emphasis. Also it would be helpful if joint permanent appointments could be established between anatomy and radiology departments. This might attract more medical graduates into anatomy departments and career anatomists trained in the essentials of radiology might, by assisting in the more routine investigations, spare the expert radiologist for the highly specialised techniques. In the field of research, especially with the advent of the various scanning techniques, students reading for an intercalated B.SC. could be involved in radiological projects. After qualifying, such students could fortify the staffing of radiology and anatomy departments, particularly if they held joint appointments.
Finally, the reason a student may not know the position of the spleen (which will surely have been taught) is that anatomy teaching time has been so curtailed (to be replaced by more fashionable subjects) and the general congestion of the whole curriculum is so great that the student has 1. Br. med.
J. 1968, ii,
48.
