- Email: [email protected]
ATOPY AND CANCER
1402 but neither Moroshima4 nor Moya et al.5 found that this improved the condition of the newborn infant as judged by the Apgar score. But increasing degrees of hyperventilation interfere with the exchange of blood-gases across the placenta, produce severe foetal acidosis, and adversely affect the clinical state of the baby at birth. From the work of Moya and his colleagues5 it seems that the critical level of maternal arterial Peo2 is 17 mm. Hg: below this there is likely to be sufficient fcetal acidosis to delay the onset of respiration. This is a very low level of arterial carbon-dioxide tension, unlikely to be brought about by hyperventilation. But some can breathe so rapidly and so deeply in hysterical patients labour that tetany with carpopedal spasm may follow; it would be interesting to establish how low the arterial Pco2 falls in these patients. A more likely danger is the use of artificial hyperventilation when the patient is under general anaesthesia for cassarean section. In order to help the surgeon in the early stages of the operation the anaesthetist may use muscle relaxants (which do not cross the placenta) in preference to deep anaesthesia (which tends to depress the foetal respiratory centre). Artificial ventilation is part of the technique, and there is always a risk of overventilation. There is need for caution here and for more precise information about possible harmful effects on the newborn infant.
spontaneous
BUY WINE AND MILK
THE Old Testament invitation to buy wine and milk without money may have had more to it than the attraction of a gift. On an empty stomach, 90% of a single dose of alcohol has been absorbed by the end of one hour,6 but this rate is much reduced if the alcohol is taken after a meal. Milk and other fatty foods, such as cream and olive oil, are widely held to inhibit alcohol absorption, because, it is thought, these less permeable foods coat the stomach. But fatty foods are not alone in this action, for Tuovinenfound that a good helping of mashed potatoes was a potent inhibitor of alcohol absorption and even beer had some retarding effect. Increased metabolism of alcohol may also account for its reduced potency after food.8 Miller et al. have now investigated the absorption of single doses of 25 ml. of alcohol in 10 subjects after they had taken 11/2 pints of water on one occasion and 11/2 pints of milk on another. The effect of the milk was to reduce the average maximum concentration of alcohol in the blood by nearly 50%-from about 35 to about 20 mg. per 100 ml. Although no objective tests of central nervous activity were carried out, signs of intoxication seemed to be reduced by taking milk first. Without milk ’all the 5 women and 3 of the men showed signs of intoxication. After milk, the effects were reduced in all the 8 previously affected, 5 of whom seemed entirely sober and the other 3 were just mildly sleepy. While this study does not decide whether this effect is due to delayed absorption or to increased rate of metabolism, it confirms the value of milk in the prevention of intoxication. Habituation does not significantly alter the rate of absorption, for chronic alcoholics seem to absorb alcohol from the gastrointestinal tract at least as 6. 7. 8. 9.
Muehlberger, C. W. J. Am. med. Ass. 1958, 167, 1842. Tuovinen, P. I. Skand. Arch. Physiol. 1930, 60, 1. Miller, D. S., Stirling, J. L. Proc. Nutr. Soc. 1966, 25, 40. Miller, D. S., Stirling, J. L., Yudkin, J. Nature, Lond. 1966, 212, 1051.
But people vary greatly in as do abstainers. 10 their response to alcohol, and it would be rash to say, therefore, that premedication with milk before the Christmas celebrations reduces the risks of combining drinking with driving or other complex and dangerous tasks.
rapidly
ATOPY AND CANCER
THE idea recurs from time to time that cancer is less in patients with certain other diseases. Sometimes the suggestion springs from the realisation that in his clinic a specialist in a non-neoplastic condition rarely, or never, encounters cancer. Often such impressions do not bear close analysis: either few of the patients concerned are of an age at which cancer might be expected or, because of preselection, patients who have cancer are not sent to the clinic in question. The impression that cancer is less common in patients with allergic disorders may or may not survive critical scrutiny; but it deserves serious attention, in view of the demonstration that immunological factors may modify, perhaps even determine, the onset of malignant disease. Mackay," at King’s College Hospital Medical School, has studied the association between allergic disorders and cancer by comparing the incidence of asthma, hayfever, nettle rash, and eczema in 150 patients with malignant disease, excluding leukxmia or reticulosis, with that in 150 control patients matched for age, sex, and area of residence. The incidence of history of one or more of the four manifestations of allergy was more than twice as high in the control group as in the probands (p < 0-01) and was entirely accounted for by the difference between the females included in the study. Thus, of 111 female cancer patients only 8 gave a history of allergy, whereas 27 of 111 female non-cancer controls did so. No special association between allergy and cancer of a particular site was observed. This report must be received cautiously, for several reasons. Firstly, cancer is not a single entity but a group of diseases in which many aetiological factors are concerned, and there is wide variation between individuals in their exposure to carcinogenic stimuli. It is possible, for reasons that may or may not be related to atopy, that Mackay’s two groups differed significantly in the extent of their exposure to one or more environmental carcinogens. Secondly, the fact that the difference was apparent only in females is not consistent with any of the more widely accepted theories of the role of immune mechanisms in the genesis of neoplastic disease. Thirdly, Mackay’s findings are at variance with those of Logan and Saker,12 though in agreement with those of Fisherman.13 Fourthly, no association, negative or positive, has been found between cancer and rheumatoid arthritis 14 or Hashimoto’s disease, 15 both of which are thought to involve a defect in immunological reactivity. common
Burnet 16
encouraged 10.
Newman,
suggested that carcinogenesis may be when the immune system is depressed, and H. W. Acute Alcoholic Intoxication.
Stanford, California,
1941. 11. 12. 13. 14. 15. 16.
Mackay, W. D. Br. J. Cancer, 1966, 20, 434. Logan, J., Saker, D. N. N.Z. med. J. 1955, 52, 210. Fisherman, E. W. J. Allergy, 1960, 31, 74. Duthie, J. J., Brown, P. E., Truelove, L. H., Baragat, F. D., Lawrie, A. J. Ann. rheum. Dis. 1964, 23, 193. Blackburn, G., O’Gorman, P. Guy’s Hosp. Rep. 1961, 110, 379. Burnet, F. M. Br. med. Bull. 1964, 20, 154.
1403 at birth were subsequently found earlier than sham-operated animals in response to chemical carcinogens.1? 18 If Mackay’s findings are confirmed, this would lead to the rather curious conclusion that patients without allergic disease are in some way immunologically defective. Unfortunately, as Mackay himself pointed out, the demonstration that patients with established cancer have a reduced capacity for forming humoral antibodies,19 for rejecting homografts,2O or for delayed hypersensitivity reactions 21 provides no clear indication of the immunological status of patients before their cancer developed. Surveys of the type reported by Mackay can be useful as pointers to further work; but without far more detailed definitions of the two factors-allergy and cancer-a negative association between the two is too uncertain to throw much light on the mechanism of
mice thymectomised to
develop
cancer
methods of training specialists: in her view set courses of instruction should be organised by regional hospital boards-which, she believes, were for this reason centred on universities with medical faculties. At the inception of the Service the medical schools had almost a monopoly of top-grade medical skill, and their special role in the region was to influence the work of the non-teaching hospitals. This, up to a point, they have done, especially in the provinces; but today, nearly 20 years later, the medical staffs of non-teaching hospitals have been strengthened and the educational influence of the teaching hospitals is less dominant. Mrs. Stevens may have underestimated the increasing amount of teaching, both undergraduate and postgraduate, done in non-teaching hospitals. Though their training capacities could be much more effectively used, as our leading article this week reiterates.
carcinogenesis. INTRAUTERINE INFECTIONS AN AMERICAN’S VIEW OF THE N.H.S.
DURING the past few years several American authors have written books about our National Health Service. Most have carried a heavy medicopolitical bias towards, or more often against, the Service. Mrs. Stevens 22 now traces the pattern of National Health Service medicine back to the origins of specialisation in the 18th century and the development of professional cleavage between consultants and general practitioners. Her assessment is objective and scrupulously fair. The referral system, whereby consultants see patients only at the request of the family doctor, came into being towards the end of the 19th century as a device to eliminate competition between general practitioners and consultants. In this way general practitioners were gradually excluded from the staffs of major voluntary hospitals. The result of these informal professional arrangements was that the physician and the surgeon retained the hospital but the general practitioner retained the patient. The panel system, introduced by the National Insurance Act of 1911, contained no financial inducement to specialisation, so that most doctors remained " generalists ". Even in 1963 seven out of every ten doctors in England were in general practice, whereas in the U.S.A. more than six out of every ten were wholly engaged in specialist practice, and many others were part-time specialists. The tripartite structure of the National Health Service perpetuated the gap between consultants and general practitioners. Based on traditional patterns of care which were not altogether appropriate for mid-20th-century medicine, the National Health Service tended to inhibit change; but Mrs. Stevens attributes much of the present dissatisfaction of general practitioners to their fierce opposition, in the early days of the Service, to payment by salary. The salaried consultant has the advantages of paid holidays, sick and study leave, junior professional help, nursing and secretarial assistance, distinction awards, and an adequate pension scheme. Mrs. Stevens rightly criticises the somewhat haphazard 17. Grant, G., Roe, F. J. C., Pike, M. C. Nature, Lond. 1966, 210, 603. 18. Trainin, N. Abstracts of papers presented at IX International Cancer
Congress, Tokyo, 1966, p. 127. 19. Lytton, B., Hughes, L. E., Fulthorpe, A. J. Lancet, 1964, i, 69. 20. Southam, C. M., Pillemer, L. Proc. Soc. exp. Biol. Med. 1957, 96, 596. 21. Hughes, L. E., Mackay, W. D. Br. med. J. 1965, ii, 1346. 22. Medical Practice in Modern England: the Impact of Specialization and State Medicine. By ROSEMARY STEVENS. New Haven and London: Yale University Press. 1966. Pp. 401. 72s.
SOME maternal infections, such as syphilis, toxoplasmosis, and those due to rubella virus and cytomegalovirus, are especially likely to damage the developing foetus, but by no means every maternal infection affects the child. The levels of immune globulins in cord blood have been examined at birth in an attempt to recognise when intrauterine infection had taken place. A technique of immunodiffusion of serum through agar gave a sensitive and fairly accurate measure of the concentrations of the three main classes of immune globulins-y G, y M, and y A. y G-globulins readily pass through the placenta and the other two do not. The levels of y G in cord blood reflect the immune status of the mother, and they are not an indication of active antibody synthesis by the child. In most normal infants, y M and y A levels at birth are very low or are undetectable, but high levels, particularly of y M macroglobulins, are found in infants congenitally infected with rubella virus. 1This observation suggests that the antibody-forming mechanism of the foetus is well developed towards the end of intrauterine life, but that it requires an antigenic stimulus, such as the presence of a virus, to provoke the formation of immune globulins. Stiehm et al. compared the levels of y M and y A globulins present in the cord blood of infants born after pregnancies known to have been complicated by infection with those found in infants born after normal pregnancies. Previous reports of raised y M and y A globulins in infants born with congenital rubella were confirmed, but unaffected infants born after pregnancies complicated by rubella, rubeola, varicella, toxoplasmosis, syphilis, and tuberculosis had normal levels of immune globulins. In addition to rubella, foetal infection by cytomegalic inclusion disease, a Coxsackie virus, and a bacteroides all produced raised levels of y M and y A globulins, and about 5% of infants born of pregnancies in which there was no history of infection also showed high globulin levels at birth, suggesting that some infections were being missed. Stiehm et al. conclude that raised levels of y M or y A globulins at birth are presumptive evidence of in-utero infection, and they suggest that such infants should be further studied in an attempt to identify their infection. 1. Alford, C. A. Am. J. Dis. Child. 1965, 110, 455. Bellanti, J. A., Artenstein, M.S., Olson, L. C., Buescher, E. L., Luhrs, C. E., Milstead, K. L. ibid. p. 464. 3. Stiehm, E. R., Ammann, A. J., Cherry, J. D. New Engl. J. Med. 1966 275, 971.
2.
spontaneous
BUY WINE AND MILK
THE Old Testament invitation to buy wine and milk without money may have had more to it than the attraction of a gift. On an empty stomach, 90% of a single dose of alcohol has been absorbed by the end of one hour,6 but this rate is much reduced if the alcohol is taken after a meal. Milk and other fatty foods, such as cream and olive oil, are widely held to inhibit alcohol absorption, because, it is thought, these less permeable foods coat the stomach. But fatty foods are not alone in this action, for Tuovinenfound that a good helping of mashed potatoes was a potent inhibitor of alcohol absorption and even beer had some retarding effect. Increased metabolism of alcohol may also account for its reduced potency after food.8 Miller et al. have now investigated the absorption of single doses of 25 ml. of alcohol in 10 subjects after they had taken 11/2 pints of water on one occasion and 11/2 pints of milk on another. The effect of the milk was to reduce the average maximum concentration of alcohol in the blood by nearly 50%-from about 35 to about 20 mg. per 100 ml. Although no objective tests of central nervous activity were carried out, signs of intoxication seemed to be reduced by taking milk first. Without milk ’all the 5 women and 3 of the men showed signs of intoxication. After milk, the effects were reduced in all the 8 previously affected, 5 of whom seemed entirely sober and the other 3 were just mildly sleepy. While this study does not decide whether this effect is due to delayed absorption or to increased rate of metabolism, it confirms the value of milk in the prevention of intoxication. Habituation does not significantly alter the rate of absorption, for chronic alcoholics seem to absorb alcohol from the gastrointestinal tract at least as 6. 7. 8. 9.
Muehlberger, C. W. J. Am. med. Ass. 1958, 167, 1842. Tuovinen, P. I. Skand. Arch. Physiol. 1930, 60, 1. Miller, D. S., Stirling, J. L. Proc. Nutr. Soc. 1966, 25, 40. Miller, D. S., Stirling, J. L., Yudkin, J. Nature, Lond. 1966, 212, 1051.
But people vary greatly in as do abstainers. 10 their response to alcohol, and it would be rash to say, therefore, that premedication with milk before the Christmas celebrations reduces the risks of combining drinking with driving or other complex and dangerous tasks.
rapidly
ATOPY AND CANCER
THE idea recurs from time to time that cancer is less in patients with certain other diseases. Sometimes the suggestion springs from the realisation that in his clinic a specialist in a non-neoplastic condition rarely, or never, encounters cancer. Often such impressions do not bear close analysis: either few of the patients concerned are of an age at which cancer might be expected or, because of preselection, patients who have cancer are not sent to the clinic in question. The impression that cancer is less common in patients with allergic disorders may or may not survive critical scrutiny; but it deserves serious attention, in view of the demonstration that immunological factors may modify, perhaps even determine, the onset of malignant disease. Mackay," at King’s College Hospital Medical School, has studied the association between allergic disorders and cancer by comparing the incidence of asthma, hayfever, nettle rash, and eczema in 150 patients with malignant disease, excluding leukxmia or reticulosis, with that in 150 control patients matched for age, sex, and area of residence. The incidence of history of one or more of the four manifestations of allergy was more than twice as high in the control group as in the probands (p < 0-01) and was entirely accounted for by the difference between the females included in the study. Thus, of 111 female cancer patients only 8 gave a history of allergy, whereas 27 of 111 female non-cancer controls did so. No special association between allergy and cancer of a particular site was observed. This report must be received cautiously, for several reasons. Firstly, cancer is not a single entity but a group of diseases in which many aetiological factors are concerned, and there is wide variation between individuals in their exposure to carcinogenic stimuli. It is possible, for reasons that may or may not be related to atopy, that Mackay’s two groups differed significantly in the extent of their exposure to one or more environmental carcinogens. Secondly, the fact that the difference was apparent only in females is not consistent with any of the more widely accepted theories of the role of immune mechanisms in the genesis of neoplastic disease. Thirdly, Mackay’s findings are at variance with those of Logan and Saker,12 though in agreement with those of Fisherman.13 Fourthly, no association, negative or positive, has been found between cancer and rheumatoid arthritis 14 or Hashimoto’s disease, 15 both of which are thought to involve a defect in immunological reactivity. common
Burnet 16
encouraged 10.
Newman,
suggested that carcinogenesis may be when the immune system is depressed, and H. W. Acute Alcoholic Intoxication.
Stanford, California,
1941. 11. 12. 13. 14. 15. 16.
Mackay, W. D. Br. J. Cancer, 1966, 20, 434. Logan, J., Saker, D. N. N.Z. med. J. 1955, 52, 210. Fisherman, E. W. J. Allergy, 1960, 31, 74. Duthie, J. J., Brown, P. E., Truelove, L. H., Baragat, F. D., Lawrie, A. J. Ann. rheum. Dis. 1964, 23, 193. Blackburn, G., O’Gorman, P. Guy’s Hosp. Rep. 1961, 110, 379. Burnet, F. M. Br. med. Bull. 1964, 20, 154.
1403 at birth were subsequently found earlier than sham-operated animals in response to chemical carcinogens.1? 18 If Mackay’s findings are confirmed, this would lead to the rather curious conclusion that patients without allergic disease are in some way immunologically defective. Unfortunately, as Mackay himself pointed out, the demonstration that patients with established cancer have a reduced capacity for forming humoral antibodies,19 for rejecting homografts,2O or for delayed hypersensitivity reactions 21 provides no clear indication of the immunological status of patients before their cancer developed. Surveys of the type reported by Mackay can be useful as pointers to further work; but without far more detailed definitions of the two factors-allergy and cancer-a negative association between the two is too uncertain to throw much light on the mechanism of
mice thymectomised to
develop
cancer
methods of training specialists: in her view set courses of instruction should be organised by regional hospital boards-which, she believes, were for this reason centred on universities with medical faculties. At the inception of the Service the medical schools had almost a monopoly of top-grade medical skill, and their special role in the region was to influence the work of the non-teaching hospitals. This, up to a point, they have done, especially in the provinces; but today, nearly 20 years later, the medical staffs of non-teaching hospitals have been strengthened and the educational influence of the teaching hospitals is less dominant. Mrs. Stevens may have underestimated the increasing amount of teaching, both undergraduate and postgraduate, done in non-teaching hospitals. Though their training capacities could be much more effectively used, as our leading article this week reiterates.
carcinogenesis. INTRAUTERINE INFECTIONS AN AMERICAN’S VIEW OF THE N.H.S.
DURING the past few years several American authors have written books about our National Health Service. Most have carried a heavy medicopolitical bias towards, or more often against, the Service. Mrs. Stevens 22 now traces the pattern of National Health Service medicine back to the origins of specialisation in the 18th century and the development of professional cleavage between consultants and general practitioners. Her assessment is objective and scrupulously fair. The referral system, whereby consultants see patients only at the request of the family doctor, came into being towards the end of the 19th century as a device to eliminate competition between general practitioners and consultants. In this way general practitioners were gradually excluded from the staffs of major voluntary hospitals. The result of these informal professional arrangements was that the physician and the surgeon retained the hospital but the general practitioner retained the patient. The panel system, introduced by the National Insurance Act of 1911, contained no financial inducement to specialisation, so that most doctors remained " generalists ". Even in 1963 seven out of every ten doctors in England were in general practice, whereas in the U.S.A. more than six out of every ten were wholly engaged in specialist practice, and many others were part-time specialists. The tripartite structure of the National Health Service perpetuated the gap between consultants and general practitioners. Based on traditional patterns of care which were not altogether appropriate for mid-20th-century medicine, the National Health Service tended to inhibit change; but Mrs. Stevens attributes much of the present dissatisfaction of general practitioners to their fierce opposition, in the early days of the Service, to payment by salary. The salaried consultant has the advantages of paid holidays, sick and study leave, junior professional help, nursing and secretarial assistance, distinction awards, and an adequate pension scheme. Mrs. Stevens rightly criticises the somewhat haphazard 17. Grant, G., Roe, F. J. C., Pike, M. C. Nature, Lond. 1966, 210, 603. 18. Trainin, N. Abstracts of papers presented at IX International Cancer
Congress, Tokyo, 1966, p. 127. 19. Lytton, B., Hughes, L. E., Fulthorpe, A. J. Lancet, 1964, i, 69. 20. Southam, C. M., Pillemer, L. Proc. Soc. exp. Biol. Med. 1957, 96, 596. 21. Hughes, L. E., Mackay, W. D. Br. med. J. 1965, ii, 1346. 22. Medical Practice in Modern England: the Impact of Specialization and State Medicine. By ROSEMARY STEVENS. New Haven and London: Yale University Press. 1966. Pp. 401. 72s.
SOME maternal infections, such as syphilis, toxoplasmosis, and those due to rubella virus and cytomegalovirus, are especially likely to damage the developing foetus, but by no means every maternal infection affects the child. The levels of immune globulins in cord blood have been examined at birth in an attempt to recognise when intrauterine infection had taken place. A technique of immunodiffusion of serum through agar gave a sensitive and fairly accurate measure of the concentrations of the three main classes of immune globulins-y G, y M, and y A. y G-globulins readily pass through the placenta and the other two do not. The levels of y G in cord blood reflect the immune status of the mother, and they are not an indication of active antibody synthesis by the child. In most normal infants, y M and y A levels at birth are very low or are undetectable, but high levels, particularly of y M macroglobulins, are found in infants congenitally infected with rubella virus. 1This observation suggests that the antibody-forming mechanism of the foetus is well developed towards the end of intrauterine life, but that it requires an antigenic stimulus, such as the presence of a virus, to provoke the formation of immune globulins. Stiehm et al. compared the levels of y M and y A globulins present in the cord blood of infants born after pregnancies known to have been complicated by infection with those found in infants born after normal pregnancies. Previous reports of raised y M and y A globulins in infants born with congenital rubella were confirmed, but unaffected infants born after pregnancies complicated by rubella, rubeola, varicella, toxoplasmosis, syphilis, and tuberculosis had normal levels of immune globulins. In addition to rubella, foetal infection by cytomegalic inclusion disease, a Coxsackie virus, and a bacteroides all produced raised levels of y M and y A globulins, and about 5% of infants born of pregnancies in which there was no history of infection also showed high globulin levels at birth, suggesting that some infections were being missed. Stiehm et al. conclude that raised levels of y M or y A globulins at birth are presumptive evidence of in-utero infection, and they suggest that such infants should be further studied in an attempt to identify their infection. 1. Alford, C. A. Am. J. Dis. Child. 1965, 110, 455. Bellanti, J. A., Artenstein, M.S., Olson, L. C., Buescher, E. L., Luhrs, C. E., Milstead, K. L. ibid. p. 464. 3. Stiehm, E. R., Ammann, A. J., Cherry, J. D. New Engl. J. Med. 1966 275, 971.
2.