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SMOKING
637 article of March 17, and I have been dealing with burns most of my life. Most burns are treated with eusol or saline solution in some form or another, and we noticed that it was in those cases that the pyocyaneus infection appeared. As soon as this happened the dressing was changed to a coal-tar lotion, usuallyCyllin ’, and the blue-green pus disappeared within a very few days. This has been my experience ever since. It has been suggested to me that the virulence of the organism may differ in different parts of the country, but I spent many years working in hospitals in the south of England so that my views are based on infections in three widely separated areas over many years. I suggest, therefore, that surgeons who are worried by pyocyaneus infections should stop putting their patients into saline baths, and stop using halogen antiseptics, and use, instead, an antiseptic of a totally different chemical nature. After the infection has been controlled, the patient can be put back on his original treatment.
Middlesbrough, ERNEST W. W W. Yorkshire.
GRAHAME.
SMOKING
I
warmly support the views of the Rev. Hubert Little (March 17) on the anti-social effects of smoking. It is only necessary to examine the ceiling of any public house to realise how soon it is discoloured by a thick deposit of tar, or even better to see what happens to the skin of a prize marrow hung up in the bar in country districts for a seed-counting competition at Christmas SIR,-May
time. I have for many years warned my patients who are heavy smokers that inhalation of second-hand shag may well halve
their expectation of life. There was also a personal experience of having reluctantly to give up attendances as a medical referee for boxing contests in a mining area. Literally everyone (except myself) smoked throughout the contest-except the contestants who could scarcely see each other through the haze. At the end of the evening, half choked, I returned to my wife, who complained bitterly of having to spend her nights with someone who smelt like a drunken tobacconist. On Sunday morning I was called to a publican with pulmonary oedema. He gave up smoking last August. But he attributed the onset of his condition and his alarming night with dypnoea to the shocking atmosphere in his crowded bar during the previous Saturday night. Walmer, Kent.
JAMES S. HALL.
WORLD POPULATION SIR,-In a leading articleyou commented on the possible risk of foetal virilisation with norethynodrel among women who fail to take the correct dose during oral contraception. This hazard might also arise when a woman starts to use an oral contraceptive when already pregnant, as inevitably happens from time to time. This emphasises the importance of selecting for oral contraceptive use a progestational steroid with oestrogenic rather than androgenic action. Norethynodrel was selected in 1956 for precisely this reason and the wisdom of this choice has since been confirmed by the numerous reports of foetal virilisation with other progestins. Your statement " Already three cases of virilisation of the foetus from norethynodrel have been recorded elsewhere " might suggest to your readers that norethynodrel is also androgenic. We know, however, of only one case of foetal virilisation in the literature-that reported by Grumbach and Ducharme2 and referred to also in other publications.34 In the recent and most comprehensive 1. Lancet, 1961, ii, 1130. 2. Grumbach, M. M., Ducharme, J. R., Moloshok, R: E. J. clin. Endocr. 1959, 19, 1369. 3. Grumbach, M. M., Ducharme, J. R. Fertil. & Steril. 1960, 11, 170. 4. Wilkins, L. Arch. Anat. micr. Morph. exp. 1959, 48, suppl. p. 313.
reviewonly one such example could be found in the world literature, presumably the same case. The choice of the word " already " in your leading article seems a strange one in connection with a drug which has been extensively used for over six years. It is estimated that at the present time approximately one million women are using this product in various parts of the world and there have been numerous other reports that this compound has been used in pregnancy without the occurrence of virilisation.6-14 It is inevitable that many coincidental occurrences will be reported when a drug is used as widely as this and the authors of the single case-report have since pointed out that this may have been the explanation of this occurrence. 15 The full evidence for the statement that norethynodrel is oestrogenic and not androgenic has been reviewed elsewhere. 16 17 G. D. Searle &
Co. Ltd.,
G. R. VENNING
High Wycombe, Bucks.
Medical Director.
LOSS OF TISSUE-SPECIFIC AUTOANTIGENS IN THYROID TUMOURS
SIR,-Dr. Irvine (March 3) is at pains to show that the evidence of autoantigen loss in thyroid tumours presented in our paper of Feb. 17 agrees with his own observations and that this evidence is not proof of Green’s 18 immunological theory of tumour formation. Is Dr. Irvine aware that no theory (" fiction ") can be proved ? It can only be
developed, supported, modified, refuted, or accepted as true; yet it may be of scientific value by leading to new discoveries. In his critical monograph on carcinogenesis Hieger 19 says that Green’s theory " is perhaps an important contribution to cancer research; until his immunological theory can be expressed clearly and directly, and until substantial experimental evidence for it becomes available, most investigators will continue to ignore its possibilities ". Our supporting experimental evidence is substantial. There is a high correlation between loss of a biologically significant autoantigen and tumour formation in the thyroid. Normal and hyperplastic cells have the antigen, some cells of most tumours do not. This change precedes invasive behaviour (the antigen is lost in premalignant lesions such as adenomata and adenomatous goitres; Dr. Irvine’s " " antigen-rich toxic adenomata must rarely, if ever, metastasise as such). We are now in a position to state Green’s theory clearly and directly.
(1) The immunity system (cells and antibodies) prevents the spread of specific tissue cells which are isolated and dislodged from their normal environment. (2) The autoimmune mechanism does not affect antigen-containing cells in their normal environment (the thriving hyperplastic cells of a toxic goitre are all damaged when isolated by trypsinisation and treated with the patient’s own cytotoxic serum). (3) Loss of autoantigen plays a permissive role in carcinogenesis by allowing dislodged and isolated cells to spread in the presence of immune cells or antibody. (4) Factors other than autoantigen loss are responsible for cell
multiplication. More facts
are now
required,
not a statement
of the
5. Wilkins, L. Acta endocr., Copenhagen, 1960, 35, suppl. 51, p. 671. 6. Rock, J., Garcia, C. R., Pincus, G. Amer. J. Obstet. Gynec. 1960, 79, 758. 7. Brit. med. J. 1960, ii, 551. 8. Tyler, E. T., Olson, H. J. J. Amer. med. Ass. 1959, 169, 1843. 9. Goldfarb, A. F., Gongsakdi, D. D. West. J. Surg. 1961, 69, 92. 10. Douglas, G. W., Weseley, A. C., Schwartzmann, E. N. Amer. J. Obstet. Gynec. 1960, 79, 665. 11. Tyler, E. T., Olson, H. J. Ann. N.Y. Acad. Sci. 1958, 71, 704. 12. Tyler, E. T.: Proceedings of a Symposium on ’Enovid’. Searle Research Laboratories, Chicago, November, 1958, p. 15. 13. Rakoff, A. E. Ann. N.Y. Acad. Sci. 1958, 71, 800. 14. Haskell, J. G. Clin. Obstet. Gynec. 1959, 2, 64. 15. Grumbach, M. M. Pacific Coast Fertility Society Meeting, Las Vegas, Nov. 12, 1960. 16. Venning, G. R. Brit. med. J. 1961, ii, 1644. 17. Drill, V. A., Riegel, B. Rec. Progr. Hormone Res. 1958, 14, 29 18. Green, H. N. Brit. med. J. 1954, ii, 1374. 19. Hieger, I. Carcinogenesis; p. 34. New York, 1961.
Middlesbrough, ERNEST W. W W. Yorkshire.
GRAHAME.
SMOKING
I
warmly support the views of the Rev. Hubert Little (March 17) on the anti-social effects of smoking. It is only necessary to examine the ceiling of any public house to realise how soon it is discoloured by a thick deposit of tar, or even better to see what happens to the skin of a prize marrow hung up in the bar in country districts for a seed-counting competition at Christmas SIR,-May
time. I have for many years warned my patients who are heavy smokers that inhalation of second-hand shag may well halve
their expectation of life. There was also a personal experience of having reluctantly to give up attendances as a medical referee for boxing contests in a mining area. Literally everyone (except myself) smoked throughout the contest-except the contestants who could scarcely see each other through the haze. At the end of the evening, half choked, I returned to my wife, who complained bitterly of having to spend her nights with someone who smelt like a drunken tobacconist. On Sunday morning I was called to a publican with pulmonary oedema. He gave up smoking last August. But he attributed the onset of his condition and his alarming night with dypnoea to the shocking atmosphere in his crowded bar during the previous Saturday night. Walmer, Kent.
JAMES S. HALL.
WORLD POPULATION SIR,-In a leading articleyou commented on the possible risk of foetal virilisation with norethynodrel among women who fail to take the correct dose during oral contraception. This hazard might also arise when a woman starts to use an oral contraceptive when already pregnant, as inevitably happens from time to time. This emphasises the importance of selecting for oral contraceptive use a progestational steroid with oestrogenic rather than androgenic action. Norethynodrel was selected in 1956 for precisely this reason and the wisdom of this choice has since been confirmed by the numerous reports of foetal virilisation with other progestins. Your statement " Already three cases of virilisation of the foetus from norethynodrel have been recorded elsewhere " might suggest to your readers that norethynodrel is also androgenic. We know, however, of only one case of foetal virilisation in the literature-that reported by Grumbach and Ducharme2 and referred to also in other publications.34 In the recent and most comprehensive 1. Lancet, 1961, ii, 1130. 2. Grumbach, M. M., Ducharme, J. R., Moloshok, R: E. J. clin. Endocr. 1959, 19, 1369. 3. Grumbach, M. M., Ducharme, J. R. Fertil. & Steril. 1960, 11, 170. 4. Wilkins, L. Arch. Anat. micr. Morph. exp. 1959, 48, suppl. p. 313.
reviewonly one such example could be found in the world literature, presumably the same case. The choice of the word " already " in your leading article seems a strange one in connection with a drug which has been extensively used for over six years. It is estimated that at the present time approximately one million women are using this product in various parts of the world and there have been numerous other reports that this compound has been used in pregnancy without the occurrence of virilisation.6-14 It is inevitable that many coincidental occurrences will be reported when a drug is used as widely as this and the authors of the single case-report have since pointed out that this may have been the explanation of this occurrence. 15 The full evidence for the statement that norethynodrel is oestrogenic and not androgenic has been reviewed elsewhere. 16 17 G. D. Searle &
Co. Ltd.,
G. R. VENNING
High Wycombe, Bucks.
Medical Director.
LOSS OF TISSUE-SPECIFIC AUTOANTIGENS IN THYROID TUMOURS
SIR,-Dr. Irvine (March 3) is at pains to show that the evidence of autoantigen loss in thyroid tumours presented in our paper of Feb. 17 agrees with his own observations and that this evidence is not proof of Green’s 18 immunological theory of tumour formation. Is Dr. Irvine aware that no theory (" fiction ") can be proved ? It can only be
developed, supported, modified, refuted, or accepted as true; yet it may be of scientific value by leading to new discoveries. In his critical monograph on carcinogenesis Hieger 19 says that Green’s theory " is perhaps an important contribution to cancer research; until his immunological theory can be expressed clearly and directly, and until substantial experimental evidence for it becomes available, most investigators will continue to ignore its possibilities ". Our supporting experimental evidence is substantial. There is a high correlation between loss of a biologically significant autoantigen and tumour formation in the thyroid. Normal and hyperplastic cells have the antigen, some cells of most tumours do not. This change precedes invasive behaviour (the antigen is lost in premalignant lesions such as adenomata and adenomatous goitres; Dr. Irvine’s " " antigen-rich toxic adenomata must rarely, if ever, metastasise as such). We are now in a position to state Green’s theory clearly and directly.
(1) The immunity system (cells and antibodies) prevents the spread of specific tissue cells which are isolated and dislodged from their normal environment. (2) The autoimmune mechanism does not affect antigen-containing cells in their normal environment (the thriving hyperplastic cells of a toxic goitre are all damaged when isolated by trypsinisation and treated with the patient’s own cytotoxic serum). (3) Loss of autoantigen plays a permissive role in carcinogenesis by allowing dislodged and isolated cells to spread in the presence of immune cells or antibody. (4) Factors other than autoantigen loss are responsible for cell
multiplication. More facts
are now
required,
not a statement
of the
5. Wilkins, L. Acta endocr., Copenhagen, 1960, 35, suppl. 51, p. 671. 6. Rock, J., Garcia, C. R., Pincus, G. Amer. J. Obstet. Gynec. 1960, 79, 758. 7. Brit. med. J. 1960, ii, 551. 8. Tyler, E. T., Olson, H. J. J. Amer. med. Ass. 1959, 169, 1843. 9. Goldfarb, A. F., Gongsakdi, D. D. West. J. Surg. 1961, 69, 92. 10. Douglas, G. W., Weseley, A. C., Schwartzmann, E. N. Amer. J. Obstet. Gynec. 1960, 79, 665. 11. Tyler, E. T., Olson, H. J. Ann. N.Y. Acad. Sci. 1958, 71, 704. 12. Tyler, E. T.: Proceedings of a Symposium on ’Enovid’. Searle Research Laboratories, Chicago, November, 1958, p. 15. 13. Rakoff, A. E. Ann. N.Y. Acad. Sci. 1958, 71, 800. 14. Haskell, J. G. Clin. Obstet. Gynec. 1959, 2, 64. 15. Grumbach, M. M. Pacific Coast Fertility Society Meeting, Las Vegas, Nov. 12, 1960. 16. Venning, G. R. Brit. med. J. 1961, ii, 1644. 17. Drill, V. A., Riegel, B. Rec. Progr. Hormone Res. 1958, 14, 29 18. Green, H. N. Brit. med. J. 1954, ii, 1374. 19. Hieger, I. Carcinogenesis; p. 34. New York, 1961.