412
be advanced,5the exact mechanism of neither the induction nor the acceleration is understood. But again it has been tempting for the experimentalist to suppose a causal relationship between virus and cancer. Those more cautious have, however, observed that in other strains, of mice comparable viruses do not seem to lead to leukaemia.6Thus it can be argued that the presence of the virus itself is not enough and that genetic predisposition and perhaps environmental influences are also involved. In man the same kinds of argument can be adopted but more on epidemiological than experimental evidence. Thus the virtual ubiquity of bone sarcoma among those who painted watch dials with radioactive material’ betokened a clear one-to-one causal relationship between radioactivity and cancer. In such circumstances it would be reasonable to suppose, as Muller did,8 that the radiation induces a mutation in the genetic material of a cell in the appropriate epithelium. In retinoblastoma of childhood the predominant evidence is for the existence of a predisposing genetic change, probably in the long arm of chromosome 13.9 10 Again the genetic deletion is easily regarded as the cause of the cancer, but the change is probably present in every cell in the body whereas the cancers are initiated in pnly very few cells. Furthermore, a deletion per se can hardly be directly causal, although it may cause a genetic imbalance which can
predisposes to malignant change. The argument vis-a-vis smoking illustrates the point better, in that the epidemiological evidence for smoking as a cause of cancer seems overwhelming" but has also been held possibly to indicate an association between genetic predisposition to cancer12 and the smoking habit. The general difficulty that has been experienced in pointing to a single predominant chemical carcinogen in cigarette smoke13 has also detracted from the apparent certainty of the epidemiological data. Whatever the truth of the matter, it is fortunately clear that not all people who smoke get lung cancer, despite the damage to their lungs caused by smoking; nor are all lung cancers caused by smoking. Thus, in mice and men, it is occasionally convenient to think in terms of single causes for the single event - onset of clonal cancer-but clearly this is quite unsatisfactory in mechanistic terms. Latterly Jarrett and his colleagues14 have examined the development of certain carcinomas in what veterinary surgeons call the bovine. Their th9rough analysis serves to re-emphasise that many if not all cancers must be supposed to have a multifactorial aetiology. In the upland areas of Scotland and northern England, and in certain other parts of the world, the cattle have a remarkably high incidence of squamous carcinoma of the upper alimentary tract. Jarrett and his colleagues found that most of the affected animals had papillomatosis at the exact sites of occurrence
of the
tumours
and many had in addition
neo-
5. Rudali, G., Duplan, J. F., Latarjet, R. C. r. Acad. Sci. Paris, 1956, 247, 837. 6. Miller, J. F. A. P. Adv. Cancer Res. 1961, 6, 291. 7. Martland, H. S. Am. J. Cancer, 1931, 15, 2435. 8. Muller, H. J. Science, 1927, 66, 84. 9. Wilson, M. G., Towner, J. W., Fujimoto, A. Am. J. hum. Genet. 1973, 25, 57. 10. McKusick, V. A. Mendelian Inheritance in Man. Baltimore, 1975. 11. Royal College of Physicians of London. Smoking or Health. London, 1977. 12. Burch, P. R. J. The Biology of Smoking, a new approach; p. 303. Lancaster, 1976. 13. Cook, J. W. Lancet, 1957, i, 333. 14. Jarrett, W. F. H., McNeil, P. E., Grimshaw, W. T. R., Selman, I. E. McIntyre, W. I. M. Nature, 1978, 274, 215.
plastic changes in the intestine and bladder. From papillomas a virus was isolated which was morphologically similar to the bovine cutaneous-papilloma virus. The virus isolated from the oesophageal papillomas caused fibromas and papillomas when injected into normal cattle but not (so far) malignant growth. In some instances it was impossible to escape the conclusion that papillomas were giving rise to squamous carcinomas. Thus the aetiological chain seemed almost complete. And yet, as Jarrett emphasises, the most likely causal agent of squamous carcinoma of the oesophagus in the western highlands of Scotland is the bracken fern, Pteridium aquilinum. In the adjacent lowland areas, with genetically comparable cattle herds, few squamous carcinomas are found. We are not told the extent to which papillomatosis and the papilloma virus occur, nor the frequency of bracken fern. All that is explicit is that on the hill farms bracken is ubiquitous whereas on the lowland farms (by inference) it is less common. In some parts of the world in which tumours of the alimentary tract occur in cattle, bracken is present but not obviously the virus. Also the associated neoplasms in intestine and bladder are seemingly not present to the same extent as in Scotland. Does the bracken cause papillomatosis only in virus-infected cattle? Does the bracken, with its radiomimetic constituents, cause mutational changes in already virus-infected cells? These questions will not be easily answered, but what is clear is that in multifactorial aetiologies, in which several independent agencies are required to engender the "catastrophic" tumour, elimination of any single agency will reduce but not necessarily eliminate the undesired end-result. In relation to cattle herds it has been claimed that elimination of bracken can reduce the incidence of tumours. 15 In man, by analogy, reduction in smoking habits would in the long run lead to a reduction in bronchial carcinoma. "
APHTHOUS IMMUNOLOGY MINOR recurrent aphthous ulcers are shallow painful lesions which heal within ten days without scarring. Major oral aphthae are large deep craters, often painful enough to interfere with speaking, eating, and swallowing ; the oral ulcers in Behçet’s syndrome are very similar. The immunological aspects of these lesions have attracted much attention since Lehner reported antibody to,2 and enhanced lymphocyte stimulation by,3 fetal oral mucosal antigen in aphthous patients; these abnormalities were even more striking in Behcet’s syndrome. One suggestion is that the disease is mediated by peripheral-blood lymphocytes, which in aphthous patients are cytotoxic for oral epithelial cells.4 5 Another is that streptococcal6 or viral’ antigens are the culprits, acting alone or as haptens in the mucosa. The lymphocyte and histiocyte infiltration of early lesions68 is con15.
Dobereiner, J., Tokarnia, C. H., Canella, C. F. C. Pesq. Agropec. Bras. 1967, 2, 489. 1. Truelove, S. C., Morris-Owen, R. M. Br. med. J. 1958, i, 603. 2. Lehner, T. Lancet, 1964, ii, 1154. 3. Lehner, T. Immunology, 1967, 13, 159. 4. Dolby, A. E. ibid. 1969, 17, 709. 5. Rogers, R. S., Sams, W. M., Shorter, R. G. Archs Derm. 1974, 109, 361. 6. Graykowski, E. A., Barile, M. F., Lee, W. B., Stanley, H. R. J. Am. med. Ass. 1966, 196, 637. 7. Sallay, K., Dan, P., Kulcsar, G., Nasz, L. Rev. Immun. 1971, 35, 17. 8. Lehner, T. J. Path. 1969, 97, 481.
413
sistent with the notion that recurrent aphthous ulceration is initiated by a cell-mediated response. Concordance studies on a small number of pairs of twins have provided some evidence that susceptibility to recurrent aphthous ulcers is genetically influenced. One might therefore expect the altered immune responsiveness to be linked with HLA type, but results here have been conflicting.10-12 Circulating immune complexes have been detected, by two techniques, in the blood of some patients with recurrent aphthous ulcers and Behçet’s syndrome.13 14 Serum C9 is raised in both conditions, more so in Behçet’s.15 Immunoglobulin and complement are demonstrable in aphthous lesions,8 but the relevance of these is doubtful since they are to be found in normal mucosa.’6 In Behet’s syndrome, but not in recurrent aphthous ulcers, the saliva and jejunal secretion lack secretory component. 17 The reduction in symptoms observed with disodium cromoglycate,18 an inhibitor of type-I-induced histamine release, also suggests that there is a humoral component in the pathogenesis of the disease. One attractive unifying concept of the pathogenesis of recurrent aphthous ulcers is based on the benefits in some patients of levamisole therapy.19 Discussing their clinical trial, Lehner and his colleagues fashionably suggested that in health a suppressor T-cell population inhibits B-cell synthesis of antibody against oral mucosa. Aphthous-ulcer patients, they postulated, have a weak suppressor T-cell population which is sufficiently stimulated by levamisole2O to control the ulcers. Alternatively, in the normal subject oral mucosal or skin antigens may circulate in low concentrations in the blood, inducing specific unresponsiveness in T but not B cells.21 22 This low dose tolerance could be abrogated in recurrent aphthous ulceration by oral microbial haptens binding to the mucosa to induce autoantibody formation or cytotoxic T cells. This emphasis on immunological mechanisms has been challenged. In a Glasgow survey,23 deficiencies of iron, folate, and vitamin B12 were detected in 17.7% of 130 aphthous-ulcer patients, compared with 8.5% of matched controls. Challacombe and colleagues24 found only iron deficiency (not anaemia) to be commoner in aphthous-ulcer patients than in controls. A Birmingham gastroenterological unit then reported that 8 out of 33 patients presenting with aphthous ulcers had histological changes in jejunal biopsy specimens compatible with coeliac disease. The oral ulceration in these 8 patients 9.
Miller, M. F., Garfunkel, A. A., Ram, C., Ship, I. I. Oral Surg. 1977, 43,
10. 11.
Platz, P., Ryder, L. P., Donatsky, O. Tissue Antigens, 1976, 8, 279. Dolby, A. E., Walker, D. M., Slade, M., Allan, C. J. J. dent. Res. 1977, 56,
886.
105. 12. Challacombe, S. J., Batchelor, J. R., Kennedy, L. A., Lehner, T. Archs Derm. 1977, 113, 1717. 13. Williams, B. D., Lehner, T. Br. med. J. 1977, i, 1387. 14. Levinsky, R. J., Lehner, T. Clin. exp. Immun. 1978, 32, 193. 15. Adolfini, M., Lehner, T. ibid. 1976, 25, 36. 16. Brandtzaeg, P. in Oral Mucosa in Health and Disease (edited by A. E. Dol-
by); p. 178. 1976. Abdou, N. I., Schumacher, H. R., Colman, R. W., Sagawa, A., Herbert, J., Pascual, E., Carroll, E. T., Miller, M., South, M. A., Abdou, N. J. Lab. clin.Med. 1978, 91, 409. 18. Frost, M. Lancet, 1973, ii, 389. 19. Lehner, T., Wilton, J. M. A., Ivanyi, L. ibid. 1976, ii, 926. 20. Sampson, D., Lui, A. Cancer Res. 1976, 36, 952. 21. Allison, A. C., Lancet, 1971, ii, 135. 22. Bankhurst, A. D., Torrigiani, G., Allison, A. C. ibid. 1973, i, 276. 23. Wray, D., Ferguson, M. M., Mason, D. K., Hutcheon, A. W., Dagg, J. H. Br. med. J. 1975, i, 490. 24. Challacombe, S. J., Barkman, P., Lehner, T. Br. J. oral Surg. 1977, 15, 37.
remitted completely on a gluten-free diet. 25 Subsequent work suggests that this is a sizeable overestimate of the prevalence of underlying coeliac disease in aphthous-ulcer patients.24 26 However, gluten could be toxic locally to the oral mucosa, since the oral ulcers of hæmatologically normal patients with normal jejunal biopsies became fewer and less painful on a gluten-free diet.27 Further studies of the development of the oral lesions-particularly immunological characterisation of the early infiltrate-might reveal basic differences or essential similarities between uncomplicated aphthæ in recurrent aphthous ulceration and Behçet’s syndrome and those clinically indistinguishable ulcers which in a small minority of patients are the presenting symptom of an underlying generalised deficiency disorder. But at present there is much in favour of Touraine’s28 view that recurrent aphthous ulcers and Beh4;et’s syndrome represent opposite ends of an "aphthosis" spectrum.
PASSIVE SMOKING AND ANGINA
growing awareness of the discomfort caused ordinary people (i.e., non-smokers) by those who smoke in their presence. Many normal people complain of stinging of the eyes or discomfort in the nose or throat in the presence of smokers, and 37% of non-smokers stated that they minded if people smoked in their homes. THERE is
to
Discomfort can be worse for sufferers from asthma or bronchitis. Until lately there has been scant evidence on the effect of passive smoking on patients with heart disease. Aronow has already shown that after smoking a cigarette1 or travelling in heavy Los Angeles traffic2 the patient with angina needs less exercise time to bring on pain. His latest study shows that even exposure to the reduce the cigarette smoke of others will significantly duration of exercise leading to angina.3 10 patients with angina (8 of them ex-smokers and 2 light smokers who had not smoked for sixteen hours) were exposed to 3 smokers in a small room who consumed five cigarettes each over two hours. The room was either well ventilated or not ventilated. In both situations the resting heart-rate, blood-pressure, and carboxyhaemoglobin levels were increased but more so when the patients were in the non-ventilated room. The duration of exercise until angina developed was decreased by 22% after passive smoking in the well ventilated room and by 38% in the non-ventilated room. It was concluded that passive smoking aggravates angina. Whether this was due to carbon monoxide, to nicotine, or to other compounds of tobacco smoke (which include nitrites of oxygen and hydrogen cyanide) was not known. The possibility of the psychological effect of exercise in a stuffy smoky room was also considered. Carbon monoxide seems to be the chief suspect. Exposure to low levels of inhaled carbon monoxide was found to decrease exercise tolerance in patients with angina
17.
25.
Ferguson, R., Basu,
M.
K., Asquith, P., Cooke, W. T. Br. med. J. 1976, i,
11. 26. Rose, J. D. R., Smith, D. M., Allan, F. G., Sircus, W. ibid. 1978, i, 1145. 27. Walker, D. M., Dolby, A. E., Mead, J., Llewelyn, J., Rhodes, J. International Association for Dental Research British Division, annual meeting,
April, 1978. (Abstr. no. 204). Touraine, A. Bull. Soc. fr. Derm. Syph. 1940, 48, 61. Aronow, W. S., Kaplan, M. A., Jacob, D. Ann. intern. Med. 1968, 69, 529. Aronow, W. S., Harris, C. N., Isbell, M. W., et al. ibid. 1972, 77, 669. 3. Aronow, W. S. New Engl. J. Med. 1978, 299, 21.
28. 1. 2.
be advanced,5the exact mechanism of neither the induction nor the acceleration is understood. But again it has been tempting for the experimentalist to suppose a causal relationship between virus and cancer. Those more cautious have, however, observed that in other strains, of mice comparable viruses do not seem to lead to leukaemia.6Thus it can be argued that the presence of the virus itself is not enough and that genetic predisposition and perhaps environmental influences are also involved. In man the same kinds of argument can be adopted but more on epidemiological than experimental evidence. Thus the virtual ubiquity of bone sarcoma among those who painted watch dials with radioactive material’ betokened a clear one-to-one causal relationship between radioactivity and cancer. In such circumstances it would be reasonable to suppose, as Muller did,8 that the radiation induces a mutation in the genetic material of a cell in the appropriate epithelium. In retinoblastoma of childhood the predominant evidence is for the existence of a predisposing genetic change, probably in the long arm of chromosome 13.9 10 Again the genetic deletion is easily regarded as the cause of the cancer, but the change is probably present in every cell in the body whereas the cancers are initiated in pnly very few cells. Furthermore, a deletion per se can hardly be directly causal, although it may cause a genetic imbalance which can
predisposes to malignant change. The argument vis-a-vis smoking illustrates the point better, in that the epidemiological evidence for smoking as a cause of cancer seems overwhelming" but has also been held possibly to indicate an association between genetic predisposition to cancer12 and the smoking habit. The general difficulty that has been experienced in pointing to a single predominant chemical carcinogen in cigarette smoke13 has also detracted from the apparent certainty of the epidemiological data. Whatever the truth of the matter, it is fortunately clear that not all people who smoke get lung cancer, despite the damage to their lungs caused by smoking; nor are all lung cancers caused by smoking. Thus, in mice and men, it is occasionally convenient to think in terms of single causes for the single event - onset of clonal cancer-but clearly this is quite unsatisfactory in mechanistic terms. Latterly Jarrett and his colleagues14 have examined the development of certain carcinomas in what veterinary surgeons call the bovine. Their th9rough analysis serves to re-emphasise that many if not all cancers must be supposed to have a multifactorial aetiology. In the upland areas of Scotland and northern England, and in certain other parts of the world, the cattle have a remarkably high incidence of squamous carcinoma of the upper alimentary tract. Jarrett and his colleagues found that most of the affected animals had papillomatosis at the exact sites of occurrence
of the
tumours
and many had in addition
neo-
5. Rudali, G., Duplan, J. F., Latarjet, R. C. r. Acad. Sci. Paris, 1956, 247, 837. 6. Miller, J. F. A. P. Adv. Cancer Res. 1961, 6, 291. 7. Martland, H. S. Am. J. Cancer, 1931, 15, 2435. 8. Muller, H. J. Science, 1927, 66, 84. 9. Wilson, M. G., Towner, J. W., Fujimoto, A. Am. J. hum. Genet. 1973, 25, 57. 10. McKusick, V. A. Mendelian Inheritance in Man. Baltimore, 1975. 11. Royal College of Physicians of London. Smoking or Health. London, 1977. 12. Burch, P. R. J. The Biology of Smoking, a new approach; p. 303. Lancaster, 1976. 13. Cook, J. W. Lancet, 1957, i, 333. 14. Jarrett, W. F. H., McNeil, P. E., Grimshaw, W. T. R., Selman, I. E. McIntyre, W. I. M. Nature, 1978, 274, 215.
plastic changes in the intestine and bladder. From papillomas a virus was isolated which was morphologically similar to the bovine cutaneous-papilloma virus. The virus isolated from the oesophageal papillomas caused fibromas and papillomas when injected into normal cattle but not (so far) malignant growth. In some instances it was impossible to escape the conclusion that papillomas were giving rise to squamous carcinomas. Thus the aetiological chain seemed almost complete. And yet, as Jarrett emphasises, the most likely causal agent of squamous carcinoma of the oesophagus in the western highlands of Scotland is the bracken fern, Pteridium aquilinum. In the adjacent lowland areas, with genetically comparable cattle herds, few squamous carcinomas are found. We are not told the extent to which papillomatosis and the papilloma virus occur, nor the frequency of bracken fern. All that is explicit is that on the hill farms bracken is ubiquitous whereas on the lowland farms (by inference) it is less common. In some parts of the world in which tumours of the alimentary tract occur in cattle, bracken is present but not obviously the virus. Also the associated neoplasms in intestine and bladder are seemingly not present to the same extent as in Scotland. Does the bracken cause papillomatosis only in virus-infected cattle? Does the bracken, with its radiomimetic constituents, cause mutational changes in already virus-infected cells? These questions will not be easily answered, but what is clear is that in multifactorial aetiologies, in which several independent agencies are required to engender the "catastrophic" tumour, elimination of any single agency will reduce but not necessarily eliminate the undesired end-result. In relation to cattle herds it has been claimed that elimination of bracken can reduce the incidence of tumours. 15 In man, by analogy, reduction in smoking habits would in the long run lead to a reduction in bronchial carcinoma. "
APHTHOUS IMMUNOLOGY MINOR recurrent aphthous ulcers are shallow painful lesions which heal within ten days without scarring. Major oral aphthae are large deep craters, often painful enough to interfere with speaking, eating, and swallowing ; the oral ulcers in Behçet’s syndrome are very similar. The immunological aspects of these lesions have attracted much attention since Lehner reported antibody to,2 and enhanced lymphocyte stimulation by,3 fetal oral mucosal antigen in aphthous patients; these abnormalities were even more striking in Behcet’s syndrome. One suggestion is that the disease is mediated by peripheral-blood lymphocytes, which in aphthous patients are cytotoxic for oral epithelial cells.4 5 Another is that streptococcal6 or viral’ antigens are the culprits, acting alone or as haptens in the mucosa. The lymphocyte and histiocyte infiltration of early lesions68 is con15.
Dobereiner, J., Tokarnia, C. H., Canella, C. F. C. Pesq. Agropec. Bras. 1967, 2, 489. 1. Truelove, S. C., Morris-Owen, R. M. Br. med. J. 1958, i, 603. 2. Lehner, T. Lancet, 1964, ii, 1154. 3. Lehner, T. Immunology, 1967, 13, 159. 4. Dolby, A. E. ibid. 1969, 17, 709. 5. Rogers, R. S., Sams, W. M., Shorter, R. G. Archs Derm. 1974, 109, 361. 6. Graykowski, E. A., Barile, M. F., Lee, W. B., Stanley, H. R. J. Am. med. Ass. 1966, 196, 637. 7. Sallay, K., Dan, P., Kulcsar, G., Nasz, L. Rev. Immun. 1971, 35, 17. 8. Lehner, T. J. Path. 1969, 97, 481.
413
sistent with the notion that recurrent aphthous ulceration is initiated by a cell-mediated response. Concordance studies on a small number of pairs of twins have provided some evidence that susceptibility to recurrent aphthous ulcers is genetically influenced. One might therefore expect the altered immune responsiveness to be linked with HLA type, but results here have been conflicting.10-12 Circulating immune complexes have been detected, by two techniques, in the blood of some patients with recurrent aphthous ulcers and Behçet’s syndrome.13 14 Serum C9 is raised in both conditions, more so in Behçet’s.15 Immunoglobulin and complement are demonstrable in aphthous lesions,8 but the relevance of these is doubtful since they are to be found in normal mucosa.’6 In Behet’s syndrome, but not in recurrent aphthous ulcers, the saliva and jejunal secretion lack secretory component. 17 The reduction in symptoms observed with disodium cromoglycate,18 an inhibitor of type-I-induced histamine release, also suggests that there is a humoral component in the pathogenesis of the disease. One attractive unifying concept of the pathogenesis of recurrent aphthous ulcers is based on the benefits in some patients of levamisole therapy.19 Discussing their clinical trial, Lehner and his colleagues fashionably suggested that in health a suppressor T-cell population inhibits B-cell synthesis of antibody against oral mucosa. Aphthous-ulcer patients, they postulated, have a weak suppressor T-cell population which is sufficiently stimulated by levamisole2O to control the ulcers. Alternatively, in the normal subject oral mucosal or skin antigens may circulate in low concentrations in the blood, inducing specific unresponsiveness in T but not B cells.21 22 This low dose tolerance could be abrogated in recurrent aphthous ulceration by oral microbial haptens binding to the mucosa to induce autoantibody formation or cytotoxic T cells. This emphasis on immunological mechanisms has been challenged. In a Glasgow survey,23 deficiencies of iron, folate, and vitamin B12 were detected in 17.7% of 130 aphthous-ulcer patients, compared with 8.5% of matched controls. Challacombe and colleagues24 found only iron deficiency (not anaemia) to be commoner in aphthous-ulcer patients than in controls. A Birmingham gastroenterological unit then reported that 8 out of 33 patients presenting with aphthous ulcers had histological changes in jejunal biopsy specimens compatible with coeliac disease. The oral ulceration in these 8 patients 9.
Miller, M. F., Garfunkel, A. A., Ram, C., Ship, I. I. Oral Surg. 1977, 43,
10. 11.
Platz, P., Ryder, L. P., Donatsky, O. Tissue Antigens, 1976, 8, 279. Dolby, A. E., Walker, D. M., Slade, M., Allan, C. J. J. dent. Res. 1977, 56,
886.
105. 12. Challacombe, S. J., Batchelor, J. R., Kennedy, L. A., Lehner, T. Archs Derm. 1977, 113, 1717. 13. Williams, B. D., Lehner, T. Br. med. J. 1977, i, 1387. 14. Levinsky, R. J., Lehner, T. Clin. exp. Immun. 1978, 32, 193. 15. Adolfini, M., Lehner, T. ibid. 1976, 25, 36. 16. Brandtzaeg, P. in Oral Mucosa in Health and Disease (edited by A. E. Dol-
by); p. 178. 1976. Abdou, N. I., Schumacher, H. R., Colman, R. W., Sagawa, A., Herbert, J., Pascual, E., Carroll, E. T., Miller, M., South, M. A., Abdou, N. J. Lab. clin.Med. 1978, 91, 409. 18. Frost, M. Lancet, 1973, ii, 389. 19. Lehner, T., Wilton, J. M. A., Ivanyi, L. ibid. 1976, ii, 926. 20. Sampson, D., Lui, A. Cancer Res. 1976, 36, 952. 21. Allison, A. C., Lancet, 1971, ii, 135. 22. Bankhurst, A. D., Torrigiani, G., Allison, A. C. ibid. 1973, i, 276. 23. Wray, D., Ferguson, M. M., Mason, D. K., Hutcheon, A. W., Dagg, J. H. Br. med. J. 1975, i, 490. 24. Challacombe, S. J., Barkman, P., Lehner, T. Br. J. oral Surg. 1977, 15, 37.
remitted completely on a gluten-free diet. 25 Subsequent work suggests that this is a sizeable overestimate of the prevalence of underlying coeliac disease in aphthous-ulcer patients.24 26 However, gluten could be toxic locally to the oral mucosa, since the oral ulcers of hæmatologically normal patients with normal jejunal biopsies became fewer and less painful on a gluten-free diet.27 Further studies of the development of the oral lesions-particularly immunological characterisation of the early infiltrate-might reveal basic differences or essential similarities between uncomplicated aphthæ in recurrent aphthous ulceration and Behçet’s syndrome and those clinically indistinguishable ulcers which in a small minority of patients are the presenting symptom of an underlying generalised deficiency disorder. But at present there is much in favour of Touraine’s28 view that recurrent aphthous ulcers and Beh4;et’s syndrome represent opposite ends of an "aphthosis" spectrum.
PASSIVE SMOKING AND ANGINA
growing awareness of the discomfort caused ordinary people (i.e., non-smokers) by those who smoke in their presence. Many normal people complain of stinging of the eyes or discomfort in the nose or throat in the presence of smokers, and 37% of non-smokers stated that they minded if people smoked in their homes. THERE is
to
Discomfort can be worse for sufferers from asthma or bronchitis. Until lately there has been scant evidence on the effect of passive smoking on patients with heart disease. Aronow has already shown that after smoking a cigarette1 or travelling in heavy Los Angeles traffic2 the patient with angina needs less exercise time to bring on pain. His latest study shows that even exposure to the reduce the cigarette smoke of others will significantly duration of exercise leading to angina.3 10 patients with angina (8 of them ex-smokers and 2 light smokers who had not smoked for sixteen hours) were exposed to 3 smokers in a small room who consumed five cigarettes each over two hours. The room was either well ventilated or not ventilated. In both situations the resting heart-rate, blood-pressure, and carboxyhaemoglobin levels were increased but more so when the patients were in the non-ventilated room. The duration of exercise until angina developed was decreased by 22% after passive smoking in the well ventilated room and by 38% in the non-ventilated room. It was concluded that passive smoking aggravates angina. Whether this was due to carbon monoxide, to nicotine, or to other compounds of tobacco smoke (which include nitrites of oxygen and hydrogen cyanide) was not known. The possibility of the psychological effect of exercise in a stuffy smoky room was also considered. Carbon monoxide seems to be the chief suspect. Exposure to low levels of inhaled carbon monoxide was found to decrease exercise tolerance in patients with angina
17.
25.
Ferguson, R., Basu,
M.
K., Asquith, P., Cooke, W. T. Br. med. J. 1976, i,
11. 26. Rose, J. D. R., Smith, D. M., Allan, F. G., Sircus, W. ibid. 1978, i, 1145. 27. Walker, D. M., Dolby, A. E., Mead, J., Llewelyn, J., Rhodes, J. International Association for Dental Research British Division, annual meeting,
April, 1978. (Abstr. no. 204). Touraine, A. Bull. Soc. fr. Derm. Syph. 1940, 48, 61. Aronow, W. S., Kaplan, M. A., Jacob, D. Ann. intern. Med. 1968, 69, 529. Aronow, W. S., Harris, C. N., Isbell, M. W., et al. ibid. 1972, 77, 669. 3. Aronow, W. S. New Engl. J. Med. 1978, 299, 21.
28. 1. 2.
