132
is one of the major sites of accumulation of L.D.L. within the arterial wall these findings imply that H.D.L. may play a role in limiting the rate of cholesterol deposition as well as in promoting cholesterol removal. What are the implications of these various findings ? First and foremost, we clearly need to confirm that H.D.L. is an anti-risk factor. In particular, it is important to establish whether the apparent benefits of an increase in H.D.L. are not simply secondary to reciprocal decreases in L.D.L. or V.L.D.L. Secondly, there is need for more frequent estimation of H.D.L. levels, not only in patients with established hyperlipoproteinaemia but also in patients with premature C.H.D. or peripheral vascular disease in whom routine screening has revealed no underlying cause. At present H.D.L. is usually quantitated by measurement of the residual cholesterol in plasma after removal of V.L.D.L. and L.D.L. by precipitation with polyanion/divalent-cation mixtures, such as heparin and manganous chloridel7 or low-molecular-weight dextran sulphate and calchloride.18 cium However, immunochemical methods for quantitating either apo A-I4 19 20 or apo A-II21 look promising-especially if used in conjunction with immunochemical measurement of apo B,22 23 the major apoprotein of V.L.D.L. and L.D.L. It may be that the &bgr;/&agr; lipoprotein ratio,24 when re-expressed as the ratio of apo B/apo A in plasma, will prove to be a more useful index of risk than total cholesterol alone. Thirdly, it seems worthwhile to encourage measures which increase the concentration of H.D.L. in plasma and avoid those which have the opposite effect. In view of the association between physical inactivity, obesity, and C.H.D.,25 it is noteworthy that carbohydraterich diets tend to decrease H.D.L. levels6 whereas physical exercise increases them.26 Finally, experimental procedures designed to promote regression of atherosclerosis, such as plasma exchange in familial hypercholesterolæmia,27 should aim not only at reducing L.D.L. levels but also at conserving H.D.L. These dual objectives might best be achieved by combining the use of the continuous-flow bloodcell separator27 and the technique of affinity chromatography,28 thus enabling selective removal of L.D.L. from large volumes of plasma. 17. Manual of Laboratory Operations, Lipid Research Clinics Program. Vol. I. Lipid and Lipoprotein Analysis. DHEW publication No. (NIH). 75-628, 1974. 18. Burstein, M., Scholmck, H. R Adv. Lipid Res. 1973, 11, 67. 19. Fainaru, M., Glangeaud, M. C., Eisenberg, D. Biochim. biophys. Acta, 1975, 386, 432. 20. Karlin, J. B., Juhn, D. J., Starr, J. I., Scanu, A. M., Rubenstem, A. H. J. Lipid Res. 1976, 17, 30. 21. Mao, S. J. T., Gotto, A. M., Jackson, R. L. Biochemistry, 1975, 14, 4127. 22. Albers, J. J., Cabana, V. G., Hazzard, W. R. Metabolism, 1975, 24, 1339. 23. Thompson, G. R., Birnbaumer, M. E., Levy, R. I., Gotto, A. M. Atherosclerosis, 1976, 24, 107. 24 Rosenman, R. H, Friedman, M., Jenkins, C. D., Straus, R., Wurm, M., Kositchek, R. Am. J. Cardiol. 1967, 19, 771. 25. Jl R. Coll. Physns, 1976, 10, 213. 26. Lopez-S, A., Vial, R., Balart, H L., Arroyave, G., Atherosclerosis, 1974, 20, 1. 27. Thompson, G. R., Lowenthal, R., Myant, N. B Lancet, 1975, i, 1208. 28. Lupien, P-J., Moorjani, S., Awad, J. ibid. 1976, i, 1261.
Vaccination against Measles pre-vaccination days a measles epidemic in the United Kingdom caused between half and threequarters of a million cases: 1 patient in 15 had a potentially serious complication such as bronchitis, pneumonia, or otitis media, and altogether there might be 100 deaths, about half of them in patients with chronic disease or disability, and 35 000 serious complications, including about 600 cases of measles encephalitis.’1 In the developing world, measles is one of the leading causes of death in infancy. Mortality-rates based on hospital statistics may be misleading but rates of 6% to over 12% have been recorded in parts of tropical Africa.23 Pre-existing malnutrition, together with local taboos which restrict fluid and protein during the acute phase, contributes to the high mortality. In such areas, measles is much more a disease of early infancy than it is in temperate climates: a third of all infections may occur before the first birthday and, by three, most children living in crowded communities have had measles.4 In developing countries, the disease is often severe, with a characteristic darkening rash which may be followed by intense desquamation. Common complications are stomatitis, bronchopneumonia, laryngitis, diarrhoea, and pyoderma. Furthermore, measles may initiate a protein-losing enteropathy6 and commonly precipitates kwashiorkor;’indeed, no IN
other
acute
disease in childhood
causes
such
weight-loss.8 This is the background against which the need for measles vaccination, both in developing and industrialised countries, must be assessed. Is vaccineinduced immunity as persistent and durable as that after naturally acquired disease, or will revaccination be necessary? Are today’s vaccines suitable for widespread use? Lifelong immunity from symptomatic infection usually follows naturally acquired disease; children in the Faroe Islands who had measles in the extensive 1781 epidemic were protected when the disease became epidemic again 65 years later, although there had been no measles to boost antibody responses between these epidemics.9 It is encouraging that, after vaccination, measles haemagglutination-inhibiting (H.Ai.) antibodies have persisted during follow-up of 6-10 years, 10-12 although antibody levels induced by the further-attenuated vaccines now in general use are two to 1. Miller, D. L. Br.
med. J. 1964, ii, 75. Morley, D., Martin, W. J., Allen, L. E. Afr. med. J. 1962, 44, 12. 3. Morley, D., Martin, W. J., Allen, L. W. Afr. med. J. 1966, 16, 24. 4. Baylet, R., Dauchy, S., Rey, M. Arch. Ges. Virusforch. 1965, 16, 46. 5. Morley, D. C., Wooland, M., Martin, W. J. J. Hyg., Camb. 1963, 61, 115 6. Axton, J. H. M. Br. med. J. 1975, iii, 79. 7. Gans, B. W. Afr. med. J. 1961, 10, 33. 8. Morley, D. Br. med. J. 1969, i, 297. 9. Panum, P. L. Observations made during the epidemic of measles on the Faroe Islands in the year 1846. Published in 1849 and translated by the Delta Omega Society, Cleveland, 1940. 10. Lepow, M. L., Nankervis, G. A. J. Pediat. 1969, 75, 407. 11. Krugman, S. ibid. 1971. 78, 1. 12. Weibel, R. E., Buynak, E. B., McLean, A. A., Hilleman, M. R. Pediatrics, 1975, 56, 380. 2.
133
four fold lower and decline more rapidly than those after natural disease or the earlier less well-tolerated vaccines.11 Low antibody levels are as protective as high levels against symptomatic infection, although subclinical infection may be more frequent in people with low titres. Exposure to measles could account for persistence of antibody, but H.A.I. antibody has persisted for up to 8 years in children in institutions who had not been exposed to measles; in this group, however, the antibody did decline more rapidly than in vaccinated children who lived at home and who had been exposed to measles in the community. Now that measles vaccination is commonplace, today’s vaccinated child is less likely than his predecessors to be exposed to measles during the next 25-30 years. By then, could his antibodies have disappeared, so that he risks severe infection if he visits a measles endemic area? Only long-term surveillance can tell us the duration and quality of vaccine-induced immunity, but there is no evidence as yet that children who receive existing vaccines after the first birthday need revaccination. Against any doubts on this score must be set the estimate that, in the decade after their introduction in the U.S.A., measles vaccines saved 2400 lives and prevented 8000 cases of mental retardation and 24 million cases of measles. 13 In the U.K., measles vaccination acceptance-rates are now only about 50%. This low take-up is probably connected with the adverse publicity about whooping-cough vaccine. But the number of cases in 1973 was 54 000 and in 1974 30 00014-as against the half to threequarters of a million which used to occur during
epidemic years. Measles has often been reported in vaccinated children, but in many cases vaccine had been given before the first birthday. 15-17 Maternal antibody may suppress an active immune response." Some vaccine failures have resulted from incorrect reconstitution or storage.1S Immune responses may be poor, and so permit clinical attacks of measles among the subjects of early vaccination programmes who received inactivated and then attenuated vaccine’9 or vaccine with human immune globulin .20 21 In addition, some 3-5% of vaccinated children, although given a potent vaccine after their first birthday, develop no immune response and, if exposed to measles, may acquire unmodified disease. Revaccination is recommended for children vaccinated before the age of nine to ten 13. Bass, J. W., Halstead, S B., Fischer, G. W.,
Schydlower, M., Wiebe,
R. A,
Ching,
Podgore, I. K., Pearl, W R., J Am. med. Ass. 1976, 235,
F. M.
31. 14 Perkins, F. T. Trans. R. Soc trop. Med Hyg 1975, 69, 24. 15 Landrigan, P J J Am. med. Ass 1972, 221, 567 16. Linnemann, C. C., Dine, M. S. Am J. Dis. Child 1972, 124, 53. 17 Reynolds, D W., Start, A ibid. p 848 18 Lerman, S. J., Gold, E J. Am. med Ass. 1971, 216, 1311. 19. Watson, G I., Parry, M. J Mon. Bull. Min. Hlth publ Hlth Lab. Serv 1967
2?, 146. 20 Baratta, R. O, Ginter, M. C., Price, M. A., Walker, J W Skinner, R. G., Prather, E C., David, J. K. Pediatrics, 1970, 46, 397 21 Arbeter, A. M., Arthur, J. H., Blakeman, G J, McIntosh, K. ibid. 1972, 81, 737.
months-particularly if they have been given measles immune globulin.22 Perhaps revaccination
,
should also be considered for those children who, in earlier trials, were given killed before live vaccine, since projections suggest that, in the absence of exposure to natural disease, their antibody levels may decline to undectable levels within 15 years of vaccination.23 With existing attenuated vaccines, healthy individuals do not need immunoglobulin; but patients with chronic chest and heart disease, fibrocystic disease, and central nervous system disorders (particularly those at risk of convulsions) should be spared the chance of febrile reactions by simultaneous administration of a small dose of human immune globulin. Levels of measles H.A.I. antibody can be checked from time to time, to see whether revaccination is needed. Occasionally, attenuated vaccines may sensitise recipients so that, on exposure to naturally acquired disease, they acquire an atypical form of measles24 similar to, but generally much less severe than, that seen after exposure to measles in recipients of inactivated vaccines.2s 26 In developing countries measles vaccination raises great problems. Since mortality is high during the first years of life, vaccination should ideally be carried out at nine to ten months,11 even though in a substantial proportion of cases maternal antibody will suppress immune responses. Theoretically, revaccination after twelve months of age would overcome this difficulty, but in many countries cost is likely to rule this out. Measles vaccine readily becomes inactive in tropical climates, and maintenance of a satisfactory "cold chain" to remote rural areas may be almost impossible. 27 HENDRICKSE found that only one of twenty measles-vaccine samples obtained from field workers in Nigeria contained infectious virus.28 But if measlesvaccination campaigns can be made to work they may represent the most substantial public-health measure available to children in the developing world. The current attenuated vaccines are generally well tolerated. Fever, transient rash, and very rarely convulsions may occur some 6 to 12 days after vaccination. Vaccine gives rise to convulsions much less often than does the naturally acquired disease. Children under two years old are at greater risk than older children, and this complication might be less frequent if vaccination was withheld until after the second birthday; but even in industrialised countries measles is still a serious threat to the under-2s-particularly in crowded areas in large con22. Morbid. Mortal. Wkly Rep. Oct. 23, 1971,i, 386. 23 Watson, G. I., Nichols, J. A., Robshaw, J R. M. Jl R. Coll. Gen. Practit 1975, 25, 863. 24 Cherry, J D., Feingin, F. D , Lobes, L A, Shackelford, P. G Pediatrics, 1972, 50, 712. 25. Rauh, L. W., Schmidt, R. Am. J Dis Child, 1965, 109, 232. 26. Fulginiti, V A , Eller, J. J., Downie, A W, Kempe, C. H. J. Am med Ass. 1967, 202, 1075. 27. Buck, A. A., Dyar, R., Paffenburger, R. American Public Health Association USA 19, 1971. 28. Hendrickse, R G Trans. R. Soc. trop. Med Hyg. 1975, 69, 31.
ID Report May
134
urbations. In the more affluent rural areas, where there is less chance of exposure to measles, there may be something to be said for vaccination after age 2. Serious complications such as encephalitis are
extremely
rare.
A
retrospective study suggested
incidence of about 1-16 cases per million doses of vaccine.29 This contrasts with the 1 per thousand complication-rate with naturally acquired disease. The effect of widespread measles-vaccination campaigns on the incidence of subacute sclerosing panencephalitis (S.S.P.E.) remains to be assessed. This very rare complication is commoner in children who have had mild infections in early infancy, and administration of attenuated measles virus at such an age might conceivably increase the incidence of S.S.P.E. S.S.P.E. has indeed been observed in children who have received measles vaccine,30 but there is no evidence that widespread measles vaccination has increased the frequency of s.s.P.E.; perhaps the reduction of wild virus in the community will make S.S.P.E. rarer still. an
IS GRIEF AN ILLNESS?
"FOLLOWING this terrible accident, in which 20 peoas well as their own two children died, Mr and Mrs X were at home under heavy sedation". So might run the news item; can the physician, faced with the piteous spectacle of such devastating grief, withhold this "heavy sedation", and if he can, should he? His attitude will be determined by the degreeto which he regards grief and its manifestations as normal and, by inference, not needing treatment, or as abnormal and inviting his intervention. Engel3 ’ held that grief is indeed an illness and that it is more than just a subjective psychological experience that does not involve somatic change. After all, the cardinal features of hyperparathyroidism were thought to be purely subjective until methods were discovered for investigating and treating it. Grief is also more than just a natural reaction to a life experience. It is indeed partly a reaction, just as a burn is the natural reaction of the skin when heat is applied to it, but one would look for a discussion on burns in a textbook not of physiology but of pathology. Engel concluded that the most important reason for regarding grief as an illness is that it would thereby become a legitimate and proper subject for study by medical scientists. Since then, much work has indeed been done by psychiatrists, notably Parkes.32 It is over this last part of the argument that there is most opposition from the medical anarchists, who deplore the intrusion of organised medical care as much into what Illich calls natural death 33 as they do into mental illness34 and drug addiction.35But, as Yeats says,
ple
29. Landrigan, P. J., Witte, J. J. J. Am. med. Ass. 1973, 223, 1459. 30. Dick, G. Br. med. J. 1975, iii, 359. 31. Engel, G. L. Psychosom. Med. 1961, 23, 18. 32. Parkes, C. M. Bereavement: Studies of Grief in Adult Life. London, 1972. 33. Illich, I. Medical Nemesis; chap. 8. London, 1975. 34. Szasz, T. S. The Myth of Mental Illness. New York, 1961. 35. Szasz, T. S. Ceremonial Chemistry. London, 1975.
"Man has created death". Our notions of death, what we expect of it and how we grieve when it has happened, are never fixed and unchanged any more than our concepts of health and disease are fixed and unchanged. One of the main reasons for the 20th century alteration in our attitude to death is the decline of religion and the substitution for it of science. "The ambition of science is to elucidate the relation between man and the universe". This statement by Jacques Monod,36 with "religion" replacing "science", might have come from the pen of any theologian of the preceding two thousand years. Doctors should therefore not be surprised if, as priests of the new theology, they are asked to comfort the bereaved. Likewise, the bereaved should not be surprised if they are comforted by the comforts that their comforters know best--drugs. Writing about widows during the six months after their bereavement, Parkes said "In general, physical treatments of this kind tranquillisers and sedatives] were all that the general practitioner gave or was expected to give". 37 How do the bereaved look on their own grief? If health can be defined operationally as a state not needing drugs, then there are several studies which show that after bereavement people regard themselves as not healthy. In their survey of 46 bereaved relatives in a Glasgow general practice, Levy and Sclare38 found that three-quarters of the smokers and nearly a third of the alcohol drinkers increased their consumption of their drug. Although this may not correspond to what the newspaper calls "heavy sedation", it might be better if pharmacologically less harmful drugs such as the benzodiazepines either were more liberally supplied by doctors or were even available over the counter at pharmacies. On the other hand, if Illich is right, grief should cease to be medicalised, and the bereaved should be helped to find their own way through it, not with drugs but by letting natural emotions emerge into consciousness. There may be little difference between grief and the depression of which Sandison39 wrote: "In simple terms, those who come through the pit of depression and the temptations of self-destruction are those who know death, but they also know life more abundantly. Those who have worked through a severe depression with the help of another person need not fear again, for their joy will be greater in the future and their depression never again so
severe"..
CELL FUSION, GENETIC CARTOGRAPHY, AND
MALIGNANCY IN the long-running debate on the best way to spend money donated for cancer research-on fundamental studies of life processes, or more directly on human cancer as encountered by the clinician-an element which has received too little attention is the quality of research. In this connection, few can doubt the excellence of the research on cell fusion in the analysis of malignancy which for many years the Cancer Research Campaign has been supporting at the Sir William Dunn 36. See Lancet, 1976, i, 1421. 37. Parkes, C. M. Bereavement: Studies of Grief in Adult Life; p.170, London, 1972. 38 Levy, B, Sclare, A. B. Jl R. Coll. Gen. Practit. 1976, 26, 329. 39. Sandison, R. A. Lancet, 1972, i, 1227.
is one of the major sites of accumulation of L.D.L. within the arterial wall these findings imply that H.D.L. may play a role in limiting the rate of cholesterol deposition as well as in promoting cholesterol removal. What are the implications of these various findings ? First and foremost, we clearly need to confirm that H.D.L. is an anti-risk factor. In particular, it is important to establish whether the apparent benefits of an increase in H.D.L. are not simply secondary to reciprocal decreases in L.D.L. or V.L.D.L. Secondly, there is need for more frequent estimation of H.D.L. levels, not only in patients with established hyperlipoproteinaemia but also in patients with premature C.H.D. or peripheral vascular disease in whom routine screening has revealed no underlying cause. At present H.D.L. is usually quantitated by measurement of the residual cholesterol in plasma after removal of V.L.D.L. and L.D.L. by precipitation with polyanion/divalent-cation mixtures, such as heparin and manganous chloridel7 or low-molecular-weight dextran sulphate and calchloride.18 cium However, immunochemical methods for quantitating either apo A-I4 19 20 or apo A-II21 look promising-especially if used in conjunction with immunochemical measurement of apo B,22 23 the major apoprotein of V.L.D.L. and L.D.L. It may be that the &bgr;/&agr; lipoprotein ratio,24 when re-expressed as the ratio of apo B/apo A in plasma, will prove to be a more useful index of risk than total cholesterol alone. Thirdly, it seems worthwhile to encourage measures which increase the concentration of H.D.L. in plasma and avoid those which have the opposite effect. In view of the association between physical inactivity, obesity, and C.H.D.,25 it is noteworthy that carbohydraterich diets tend to decrease H.D.L. levels6 whereas physical exercise increases them.26 Finally, experimental procedures designed to promote regression of atherosclerosis, such as plasma exchange in familial hypercholesterolæmia,27 should aim not only at reducing L.D.L. levels but also at conserving H.D.L. These dual objectives might best be achieved by combining the use of the continuous-flow bloodcell separator27 and the technique of affinity chromatography,28 thus enabling selective removal of L.D.L. from large volumes of plasma. 17. Manual of Laboratory Operations, Lipid Research Clinics Program. Vol. I. Lipid and Lipoprotein Analysis. DHEW publication No. (NIH). 75-628, 1974. 18. Burstein, M., Scholmck, H. R Adv. Lipid Res. 1973, 11, 67. 19. Fainaru, M., Glangeaud, M. C., Eisenberg, D. Biochim. biophys. Acta, 1975, 386, 432. 20. Karlin, J. B., Juhn, D. J., Starr, J. I., Scanu, A. M., Rubenstem, A. H. J. Lipid Res. 1976, 17, 30. 21. Mao, S. J. T., Gotto, A. M., Jackson, R. L. Biochemistry, 1975, 14, 4127. 22. Albers, J. J., Cabana, V. G., Hazzard, W. R. Metabolism, 1975, 24, 1339. 23. Thompson, G. R., Birnbaumer, M. E., Levy, R. I., Gotto, A. M. Atherosclerosis, 1976, 24, 107. 24 Rosenman, R. H, Friedman, M., Jenkins, C. D., Straus, R., Wurm, M., Kositchek, R. Am. J. Cardiol. 1967, 19, 771. 25. Jl R. Coll. Physns, 1976, 10, 213. 26. Lopez-S, A., Vial, R., Balart, H L., Arroyave, G., Atherosclerosis, 1974, 20, 1. 27. Thompson, G. R., Lowenthal, R., Myant, N. B Lancet, 1975, i, 1208. 28. Lupien, P-J., Moorjani, S., Awad, J. ibid. 1976, i, 1261.
Vaccination against Measles pre-vaccination days a measles epidemic in the United Kingdom caused between half and threequarters of a million cases: 1 patient in 15 had a potentially serious complication such as bronchitis, pneumonia, or otitis media, and altogether there might be 100 deaths, about half of them in patients with chronic disease or disability, and 35 000 serious complications, including about 600 cases of measles encephalitis.’1 In the developing world, measles is one of the leading causes of death in infancy. Mortality-rates based on hospital statistics may be misleading but rates of 6% to over 12% have been recorded in parts of tropical Africa.23 Pre-existing malnutrition, together with local taboos which restrict fluid and protein during the acute phase, contributes to the high mortality. In such areas, measles is much more a disease of early infancy than it is in temperate climates: a third of all infections may occur before the first birthday and, by three, most children living in crowded communities have had measles.4 In developing countries, the disease is often severe, with a characteristic darkening rash which may be followed by intense desquamation. Common complications are stomatitis, bronchopneumonia, laryngitis, diarrhoea, and pyoderma. Furthermore, measles may initiate a protein-losing enteropathy6 and commonly precipitates kwashiorkor;’indeed, no IN
other
acute
disease in childhood
causes
such
weight-loss.8 This is the background against which the need for measles vaccination, both in developing and industrialised countries, must be assessed. Is vaccineinduced immunity as persistent and durable as that after naturally acquired disease, or will revaccination be necessary? Are today’s vaccines suitable for widespread use? Lifelong immunity from symptomatic infection usually follows naturally acquired disease; children in the Faroe Islands who had measles in the extensive 1781 epidemic were protected when the disease became epidemic again 65 years later, although there had been no measles to boost antibody responses between these epidemics.9 It is encouraging that, after vaccination, measles haemagglutination-inhibiting (H.Ai.) antibodies have persisted during follow-up of 6-10 years, 10-12 although antibody levels induced by the further-attenuated vaccines now in general use are two to 1. Miller, D. L. Br.
med. J. 1964, ii, 75. Morley, D., Martin, W. J., Allen, L. E. Afr. med. J. 1962, 44, 12. 3. Morley, D., Martin, W. J., Allen, L. W. Afr. med. J. 1966, 16, 24. 4. Baylet, R., Dauchy, S., Rey, M. Arch. Ges. Virusforch. 1965, 16, 46. 5. Morley, D. C., Wooland, M., Martin, W. J. J. Hyg., Camb. 1963, 61, 115 6. Axton, J. H. M. Br. med. J. 1975, iii, 79. 7. Gans, B. W. Afr. med. J. 1961, 10, 33. 8. Morley, D. Br. med. J. 1969, i, 297. 9. Panum, P. L. Observations made during the epidemic of measles on the Faroe Islands in the year 1846. Published in 1849 and translated by the Delta Omega Society, Cleveland, 1940. 10. Lepow, M. L., Nankervis, G. A. J. Pediat. 1969, 75, 407. 11. Krugman, S. ibid. 1971. 78, 1. 12. Weibel, R. E., Buynak, E. B., McLean, A. A., Hilleman, M. R. Pediatrics, 1975, 56, 380. 2.
133
four fold lower and decline more rapidly than those after natural disease or the earlier less well-tolerated vaccines.11 Low antibody levels are as protective as high levels against symptomatic infection, although subclinical infection may be more frequent in people with low titres. Exposure to measles could account for persistence of antibody, but H.A.I. antibody has persisted for up to 8 years in children in institutions who had not been exposed to measles; in this group, however, the antibody did decline more rapidly than in vaccinated children who lived at home and who had been exposed to measles in the community. Now that measles vaccination is commonplace, today’s vaccinated child is less likely than his predecessors to be exposed to measles during the next 25-30 years. By then, could his antibodies have disappeared, so that he risks severe infection if he visits a measles endemic area? Only long-term surveillance can tell us the duration and quality of vaccine-induced immunity, but there is no evidence as yet that children who receive existing vaccines after the first birthday need revaccination. Against any doubts on this score must be set the estimate that, in the decade after their introduction in the U.S.A., measles vaccines saved 2400 lives and prevented 8000 cases of mental retardation and 24 million cases of measles. 13 In the U.K., measles vaccination acceptance-rates are now only about 50%. This low take-up is probably connected with the adverse publicity about whooping-cough vaccine. But the number of cases in 1973 was 54 000 and in 1974 30 00014-as against the half to threequarters of a million which used to occur during
epidemic years. Measles has often been reported in vaccinated children, but in many cases vaccine had been given before the first birthday. 15-17 Maternal antibody may suppress an active immune response." Some vaccine failures have resulted from incorrect reconstitution or storage.1S Immune responses may be poor, and so permit clinical attacks of measles among the subjects of early vaccination programmes who received inactivated and then attenuated vaccine’9 or vaccine with human immune globulin .20 21 In addition, some 3-5% of vaccinated children, although given a potent vaccine after their first birthday, develop no immune response and, if exposed to measles, may acquire unmodified disease. Revaccination is recommended for children vaccinated before the age of nine to ten 13. Bass, J. W., Halstead, S B., Fischer, G. W.,
Schydlower, M., Wiebe,
R. A,
Ching,
Podgore, I. K., Pearl, W R., J Am. med. Ass. 1976, 235,
F. M.
31. 14 Perkins, F. T. Trans. R. Soc trop. Med Hyg 1975, 69, 24. 15 Landrigan, P J J Am. med. Ass 1972, 221, 567 16. Linnemann, C. C., Dine, M. S. Am J. Dis. Child 1972, 124, 53. 17 Reynolds, D W., Start, A ibid. p 848 18 Lerman, S. J., Gold, E J. Am. med Ass. 1971, 216, 1311. 19. Watson, G I., Parry, M. J Mon. Bull. Min. Hlth publ Hlth Lab. Serv 1967
2?, 146. 20 Baratta, R. O, Ginter, M. C., Price, M. A., Walker, J W Skinner, R. G., Prather, E C., David, J. K. Pediatrics, 1970, 46, 397 21 Arbeter, A. M., Arthur, J. H., Blakeman, G J, McIntosh, K. ibid. 1972, 81, 737.
months-particularly if they have been given measles immune globulin.22 Perhaps revaccination
,
should also be considered for those children who, in earlier trials, were given killed before live vaccine, since projections suggest that, in the absence of exposure to natural disease, their antibody levels may decline to undectable levels within 15 years of vaccination.23 With existing attenuated vaccines, healthy individuals do not need immunoglobulin; but patients with chronic chest and heart disease, fibrocystic disease, and central nervous system disorders (particularly those at risk of convulsions) should be spared the chance of febrile reactions by simultaneous administration of a small dose of human immune globulin. Levels of measles H.A.I. antibody can be checked from time to time, to see whether revaccination is needed. Occasionally, attenuated vaccines may sensitise recipients so that, on exposure to naturally acquired disease, they acquire an atypical form of measles24 similar to, but generally much less severe than, that seen after exposure to measles in recipients of inactivated vaccines.2s 26 In developing countries measles vaccination raises great problems. Since mortality is high during the first years of life, vaccination should ideally be carried out at nine to ten months,11 even though in a substantial proportion of cases maternal antibody will suppress immune responses. Theoretically, revaccination after twelve months of age would overcome this difficulty, but in many countries cost is likely to rule this out. Measles vaccine readily becomes inactive in tropical climates, and maintenance of a satisfactory "cold chain" to remote rural areas may be almost impossible. 27 HENDRICKSE found that only one of twenty measles-vaccine samples obtained from field workers in Nigeria contained infectious virus.28 But if measlesvaccination campaigns can be made to work they may represent the most substantial public-health measure available to children in the developing world. The current attenuated vaccines are generally well tolerated. Fever, transient rash, and very rarely convulsions may occur some 6 to 12 days after vaccination. Vaccine gives rise to convulsions much less often than does the naturally acquired disease. Children under two years old are at greater risk than older children, and this complication might be less frequent if vaccination was withheld until after the second birthday; but even in industrialised countries measles is still a serious threat to the under-2s-particularly in crowded areas in large con22. Morbid. Mortal. Wkly Rep. Oct. 23, 1971,i, 386. 23 Watson, G. I., Nichols, J. A., Robshaw, J R. M. Jl R. Coll. Gen. Practit 1975, 25, 863. 24 Cherry, J D., Feingin, F. D , Lobes, L A, Shackelford, P. G Pediatrics, 1972, 50, 712. 25. Rauh, L. W., Schmidt, R. Am. J Dis Child, 1965, 109, 232. 26. Fulginiti, V A , Eller, J. J., Downie, A W, Kempe, C. H. J. Am med Ass. 1967, 202, 1075. 27. Buck, A. A., Dyar, R., Paffenburger, R. American Public Health Association USA 19, 1971. 28. Hendrickse, R G Trans. R. Soc. trop. Med Hyg. 1975, 69, 31.
ID Report May
134
urbations. In the more affluent rural areas, where there is less chance of exposure to measles, there may be something to be said for vaccination after age 2. Serious complications such as encephalitis are
extremely
rare.
A
retrospective study suggested
incidence of about 1-16 cases per million doses of vaccine.29 This contrasts with the 1 per thousand complication-rate with naturally acquired disease. The effect of widespread measles-vaccination campaigns on the incidence of subacute sclerosing panencephalitis (S.S.P.E.) remains to be assessed. This very rare complication is commoner in children who have had mild infections in early infancy, and administration of attenuated measles virus at such an age might conceivably increase the incidence of S.S.P.E. S.S.P.E. has indeed been observed in children who have received measles vaccine,30 but there is no evidence that widespread measles vaccination has increased the frequency of s.s.P.E.; perhaps the reduction of wild virus in the community will make S.S.P.E. rarer still. an
IS GRIEF AN ILLNESS?
"FOLLOWING this terrible accident, in which 20 peoas well as their own two children died, Mr and Mrs X were at home under heavy sedation". So might run the news item; can the physician, faced with the piteous spectacle of such devastating grief, withhold this "heavy sedation", and if he can, should he? His attitude will be determined by the degreeto which he regards grief and its manifestations as normal and, by inference, not needing treatment, or as abnormal and inviting his intervention. Engel3 ’ held that grief is indeed an illness and that it is more than just a subjective psychological experience that does not involve somatic change. After all, the cardinal features of hyperparathyroidism were thought to be purely subjective until methods were discovered for investigating and treating it. Grief is also more than just a natural reaction to a life experience. It is indeed partly a reaction, just as a burn is the natural reaction of the skin when heat is applied to it, but one would look for a discussion on burns in a textbook not of physiology but of pathology. Engel concluded that the most important reason for regarding grief as an illness is that it would thereby become a legitimate and proper subject for study by medical scientists. Since then, much work has indeed been done by psychiatrists, notably Parkes.32 It is over this last part of the argument that there is most opposition from the medical anarchists, who deplore the intrusion of organised medical care as much into what Illich calls natural death 33 as they do into mental illness34 and drug addiction.35But, as Yeats says,
ple
29. Landrigan, P. J., Witte, J. J. J. Am. med. Ass. 1973, 223, 1459. 30. Dick, G. Br. med. J. 1975, iii, 359. 31. Engel, G. L. Psychosom. Med. 1961, 23, 18. 32. Parkes, C. M. Bereavement: Studies of Grief in Adult Life. London, 1972. 33. Illich, I. Medical Nemesis; chap. 8. London, 1975. 34. Szasz, T. S. The Myth of Mental Illness. New York, 1961. 35. Szasz, T. S. Ceremonial Chemistry. London, 1975.
"Man has created death". Our notions of death, what we expect of it and how we grieve when it has happened, are never fixed and unchanged any more than our concepts of health and disease are fixed and unchanged. One of the main reasons for the 20th century alteration in our attitude to death is the decline of religion and the substitution for it of science. "The ambition of science is to elucidate the relation between man and the universe". This statement by Jacques Monod,36 with "religion" replacing "science", might have come from the pen of any theologian of the preceding two thousand years. Doctors should therefore not be surprised if, as priests of the new theology, they are asked to comfort the bereaved. Likewise, the bereaved should not be surprised if they are comforted by the comforts that their comforters know best--drugs. Writing about widows during the six months after their bereavement, Parkes said "In general, physical treatments of this kind tranquillisers and sedatives] were all that the general practitioner gave or was expected to give". 37 How do the bereaved look on their own grief? If health can be defined operationally as a state not needing drugs, then there are several studies which show that after bereavement people regard themselves as not healthy. In their survey of 46 bereaved relatives in a Glasgow general practice, Levy and Sclare38 found that three-quarters of the smokers and nearly a third of the alcohol drinkers increased their consumption of their drug. Although this may not correspond to what the newspaper calls "heavy sedation", it might be better if pharmacologically less harmful drugs such as the benzodiazepines either were more liberally supplied by doctors or were even available over the counter at pharmacies. On the other hand, if Illich is right, grief should cease to be medicalised, and the bereaved should be helped to find their own way through it, not with drugs but by letting natural emotions emerge into consciousness. There may be little difference between grief and the depression of which Sandison39 wrote: "In simple terms, those who come through the pit of depression and the temptations of self-destruction are those who know death, but they also know life more abundantly. Those who have worked through a severe depression with the help of another person need not fear again, for their joy will be greater in the future and their depression never again so
severe"..
CELL FUSION, GENETIC CARTOGRAPHY, AND
MALIGNANCY IN the long-running debate on the best way to spend money donated for cancer research-on fundamental studies of life processes, or more directly on human cancer as encountered by the clinician-an element which has received too little attention is the quality of research. In this connection, few can doubt the excellence of the research on cell fusion in the analysis of malignancy which for many years the Cancer Research Campaign has been supporting at the Sir William Dunn 36. See Lancet, 1976, i, 1421. 37. Parkes, C. M. Bereavement: Studies of Grief in Adult Life; p.170, London, 1972. 38 Levy, B, Sclare, A. B. Jl R. Coll. Gen. Practit. 1976, 26, 329. 39. Sandison, R. A. Lancet, 1972, i, 1227.
