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is one of the major sites of accumulation of L.D.L.within the arterial wall these findings imply thatH.D.L. may play a role in limiting the rate of choles-terol deposition as well as in promoting cholesterolremoval.What are the implications of these various find-

ings ? First and foremost, we clearly need to con-firm that H.D.L. is an anti-risk factor. In particular,it is important to establish whether the apparentbenefits of an increase in H.D.L. are not simplysecondary to reciprocal decreases in L.D.L. or

V.L.D.L. Secondly, there is need for more frequentestimation of H.D.L. levels, not only in patients withestablished hyperlipoproteinaemia but also in pa-tients with premature C.H.D. or peripheral vasculardisease in whom routine screening has revealed nounderlying cause. At present H.D.L. is usually quan-titated by measurement of the residual cholesterolin plasma after removal of V.L.D.L. and L.D.L. byprecipitation with polyanion/divalent-cation mix-tures, such as heparin and manganous chloridel7 orlow-molecular-weight dextran sulphate and cal-cium chloride.18 However, immunochemicalmethods for quantitating either apo A-I4 19 20 orapo A-II21 look promising-especially if used in

conjunction with immunochemical measurement ofapo B,22 23 the major apoprotein of V.L.D.L. andL.D.L. It may be that the &bgr;/&agr; lipoprotein ratio,24when re-expressed as the ratio of apo B/apo A inplasma, will prove to be a more useful index of riskthan total cholesterol alone. Thirdly, it seems

worthwhile to encourage measures which increasethe concentration of H.D.L. in plasma and avoidthose which have the opposite effect. In view of theassociation between physical inactivity, obesity,and C.H.D.,25 it is noteworthy that carbohydrate-rich diets tend to decrease H.D.L. levels6 whereas

physical exercise increases them.26 Finally, experi-mental procedures designed to promote regressionof atherosclerosis, such as plasma exchange infamilial hypercholesterolæmia,27 should aim not

only at reducing L.D.L. levels but also at conservingH.D.L. These dual objectives might best be achievedby combining the use of the continuous-flow blood-cell separator27 and the technique of affinity chro-matography,28 thus enabling selective removal ofL.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. Athero-

sclerosis, 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 MeaslesIN pre-vaccination days a measles epidemic in the

United Kingdom caused between half and three-quarters of a million cases: 1 patient in 15 had apotentially serious complication such as bronchitis,pneumonia, or otitis media, and altogether theremight be 100 deaths, about half of them in patientswith chronic disease or disability, and 35 000serious complications, including about 600 cases ofmeasles encephalitis.’ 1 In the developing world,measles is one of the leading causes of death in in-fancy. Mortality-rates based on hospital statisticsmay be misleading but rates of 6% to over 12%have been recorded in parts of tropical Africa.2 3

Pre-existing malnutrition, together with local tabooswhich restrict fluid and protein during the acutephase, contributes to the high mortality. In suchareas, measles is much more a disease of early in-fancy than it is in temperate climates: a third of allinfections may occur before the first birthday and,by three, most children living in crowded com-munities have had measles.4 In developing coun-tries, the disease is often severe, with a character-istic darkening rash which may be followed byintense desquamation. Common complications arestomatitis, laryngitis, bronchopneumonia,diarrhoea, and pyoderma. Furthermore, measlesmay initiate a protein-losing enteropathy6 and

commonly precipitates kwashiorkor;’ indeed, noother acute disease in childhood causes such

weight-loss.8This is the background against which the need

for measles vaccination, both in developing and in-dustrialised countries, must be assessed. Is vaccine-induced immunity as persistent and durable as thatafter naturally acquired disease, or will revaccina-tion be necessary? Are today’s vaccines suitable forwidespread use? Lifelong immunity from sympto-matic infection usually follows naturally acquireddisease; children in the Faroe Islands who hadmeasles in the extensive 1781 epidemic were pro-tected when the disease became epidemic again 65years later, although there had been no measles toboost antibody responses between these epidemics.9It is encouraging that, after vaccination, measleshaemagglutination-inhibiting (H.Ai.) antibodieshave persisted during follow-up of 6-10 years, 10-12although antibody levels induced by the further-at-tenuated vaccines now in general use are two to1. Miller, D. L. Br. med. J. 1964, ii, 75.2. 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 theDelta 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.

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four fold lower and decline more rapidly than thoseafter natural disease or the earlier less well-to-lerated vaccines.11 Low antibody levels are as pro-tective as high levels against symptomatic infec-tion, although subclinical infection may be morefrequent 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 yearsin children in institutions who had not been

exposed to measles; in this group, however, theantibody did decline more rapidly than in vac-

cinated children who lived at home and who hadbeen exposed to measles in the community.Now that measles vaccination is commonplace,

today’s vaccinated child is less likely than his pre-decessors to be exposed to measles during the next25-30 years. By then, could his antibodies havedisappeared, so that he risks severe infection if hevisits a measles endemic area? Only long-term sur-veillance can tell us the duration and quality ofvaccine-induced immunity, but there is no evidenceas yet that children who receive existing vaccinesafter the first birthday need revaccination. Againstany doubts on this score must be set the estimatethat, in the decade after their introduction in theU.S.A., measles vaccines saved 2400 lives and pre-vented 8000 cases of mental retardation and 24million cases of measles. 13 In the U.K., measles vac-cination acceptance-rates are now only about 50%.This low take-up is probably connected with theadverse publicity about whooping-cough vaccine.But the number of cases in 1973 was 54 000 andin 1974 30 00014-as against the half to three-

quarters of a million which used to occur duringepidemic years.

Measles has often been reported in vaccinatedchildren, but in many cases vaccine had been givenbefore the first birthday. 15-17 Maternal antibodymay suppress an active immune response." Somevaccine failures have resulted from incorrect recon-stitution or storage.1S Immune responses may bepoor, and so permit clinical attacks of measles

among the subjects of early vaccination pro-

grammes who received inactivated and thenattenuated vaccine’9 or vaccine with human im-mune globulin .20 21 In addition, some 3-5% of vac-cinated children, although given a potent vaccineafter their first birthday, develop no immune re-sponse and, if exposed to measles, may acquire un-modified disease. Revaccination is recommendedfor children vaccinated before the age of nine to ten

13. Bass, J. W., Halstead, S B., Fischer, G. W., Podgore, I. K., Pearl, W R.,Schydlower, M., Wiebe, R. A, Ching, F. M. J Am. med. Ass. 1976, 235,31.

14 Perkins, F. T. Trans. R. Soc trop. Med Hyg 1975, 69, 24.15 Landrigan, P J J Am. med. Ass 1972, 221, 56716. Linnemann, C. C., Dine, M. S. Am J. Dis. Child 1972, 124, 53.17 Reynolds, D W., Start, A ibid. p 84818 Lerman, S. J., Gold, E J. Am. med Ass. 1971, 216, 1311.19. Watson, G I., Parry, J M. 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, 39721 Arbeter, A. M., Arthur, J. H., Blakeman, G J, McIntosh, K. ibid. 1972, 81,

737.

months-particularly if they have been givenmeasles immune globulin.22 Perhaps revaccinationshould also be considered for those children who, inearlier trials, were given killed before live vaccine,since projections suggest that, in the absence ofexposure to natural disease, their antibody levelsmay decline to undectable levels within 15 years ofvaccination.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 dis-orders (particularly those at risk of convulsions)should be spared the chance of febrile reactions bysimultaneous administration of a small dose ofhuman immune globulin. Levels of measles H.A.I.antibody can be checked from time to time, to seewhether revaccination is needed. Occasionally,attenuated vaccines may sensitise recipients so

that, on exposure to naturally acquired disease,they acquire an atypical form of measles24 similarto, but generally much less severe than, that seenafter exposure to measles in recipients of inacti-vated vaccines.2s 26

In developing countries measles vaccinationraises great problems. Since mortality is high dur-ing the first years of life, vaccination should ideallybe carried out at nine to ten months,11 even thoughin a substantial proportion of cases maternal anti-body will suppress immune responses. Theoreti-

cally, revaccination after twelve months of agewould overcome this difficulty, but in many coun-

tries cost is likely to rule this out. Measles vaccinereadily becomes inactive in tropical climates, andmaintenance of a satisfactory "cold chain" to

remote rural areas may be almost impossible. 27HENDRICKSE found that only one of twenty meas-les-vaccine samples obtained from field workers inNigeria contained infectious virus.28 But if measles-vaccination campaigns can be made to work theymay represent the most substantial public-healthmeasure available to children in the developingworld.The current attenuated vaccines are generally well

tolerated. Fever, transient rash, and very rarely con-vulsions may occur some 6 to 12 days after vaccina-tion. Vaccine gives rise to convulsions muchless often than does the naturally acquired disease.Children under two years old are at greater riskthan older children, and this complication might beless frequent if vaccination was withheld until afterthe second birthday; but even in industrialisedcountries measles is still a serious threat to the un-

der-2s-particularly in crowded areas in large con-

22. 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 Associa-

tion USA ID Report May 19, 1971.28. Hendrickse, R G Trans. R. Soc. trop. Med Hyg. 1975, 69, 31.

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urbations. In the more affluent rural areas, wherethere is less chance of exposure to measles, theremay be something to be said for vaccination afterage 2. Serious complications such as encephalitisare extremely rare. A retrospective study suggestedan incidence of about 1-16 cases per million dosesof vaccine.29 This contrasts with the 1 per thou-sand complication-rate with naturally acquired dis-ease. The effect of widespread measles-vaccinationcampaigns on the incidence of subacute sclerosingpanencephalitis (S.S.P.E.) remains to be assessed.This very rare complication is commoner in childrenwho have had mild infections in early infancy, andadministration of attenuated measles virus at suchan age might conceivably increase the incidence ofS.S.P.E. S.S.P.E. has indeed been observed inchildren who have received measles vaccine,30 butthere is no evidence that widespread measles vac-cination has increased the frequency of s.s.P.E.;perhaps the reduction of wild virus in the com-munity will make S.S.P.E. rarer still.

IS GRIEF AN ILLNESS?

"FOLLOWING this terrible accident, in which 20 peo-ple as well as their own two children died, Mr and MrsX were at home under heavy sedation". So might runthe news item; can the physician, faced with the piteousspectacle of such devastating grief, withhold this "heavysedation", and if he can, should he? His attitude will bedetermined by the degree to which he regards grief andits manifestations as normal and, by inference, not need-ing treatment, or as abnormal and inviting his interven-tion.

Engel3 ’ held that grief is indeed an illness and that itis more than just a subjective psychological experiencethat does not involve somatic change. After all, the car-dinal features of hyperparathyroidism were thought tobe purely subjective until methods were discovered forinvestigating and treating it. Grief is also more than justa natural reaction to a life experience. It is indeed partlya reaction, just as a burn is the natural reaction of theskin when heat is applied to it, but one would look fora discussion on burns in a textbook not of physiology butof pathology. Engel concluded that the most importantreason for regarding grief as an illness is that it wouldthereby become a legitimate and proper subject for studyby medical scientists. Since then, much work has indeedbeen done by psychiatrists, notably Parkes.32

It is over this last part of the argument that there ismost opposition from the medical anarchists, who de-plore the intrusion of organised medical care as muchinto what Illich calls natural death 33 as they do intomental illness34 and drug addiction.35 But, as Yeats says,

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 weexpect of it and how we grieve when it has happened,are never fixed and unchanged any more than our con-cepts of health and disease are fixed and unchanged.One of the main reasons for the 20th century alterationin our attitude to death is the decline of religion and thesubstitution for it of science. "The ambition of scienceis to elucidate the relation between man and the uni-verse". This statement by Jacques Monod,36 with "reli-gion" replacing "science", might have come from thepen of any theologian of the preceding two thousandyears. Doctors should therefore not be surprised if, aspriests of the new theology, they are asked to comfortthe bereaved. Likewise, the bereaved should not be sur-prised if they are comforted by the comforts that theircomforters know best--drugs. Writing about widowsduring the six months after their bereavement, Parkessaid "In general, physical treatments of this kind tran-quillisers and sedatives] were all that the general practi-tioner gave or was expected to give". 37How do the bereaved look on their own grief? If

health can be defined operationally as a state not need-ing drugs, then there are several studies which show thatafter bereavement people regard themselves as not

healthy. In their survey of 46 bereaved relatives in a

Glasgow general practice, Levy and Sclare38 found thatthree-quarters of the smokers and nearly a third of thealcohol drinkers increased their consumption of theirdrug. Although this may not correspond to what thenewspaper calls "heavy sedation", it might be better ifpharmacologically less harmful drugs such as the benzo-diazepines either were more liberally supplied by doctorsor were even available over the counter at pharmacies.On the other hand, if Illich is right, grief should ceaseto be medicalised, and the bereaved should be helped tofind their own way through it, not with drugs but by let-ting natural emotions emerge into consciousness. Theremay be little difference between grief and the depressionof which Sandison39 wrote: "In simple terms, those whocome through the pit of depression and the temptationsof self-destruction are those who know death, but theyalso know life more abundantly. Those who haveworked through a severe depression with the help ofanother person need not fear again, for their joy will begreater in the future and their depression never again sosevere"..

CELL FUSION, GENETIC CARTOGRAPHY, ANDMALIGNANCY

IN the long-running debate on the best way to spendmoney donated for cancer research-on fundamentalstudies of life processes, or more directly on humancancer as encountered by the clinician-an elementwhich has received too little attention is the quality ofresearch. In this connection, few can doubt the excel-lence of the research on cell fusion in the analysis ofmalignancy which for many years the Cancer ResearchCampaign 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.