1000
The absence of a strong correlation in the data of the collaborative study5 may be the result of In many centres maternal-serum AFP and amniotic-fluid AFP are measured by difficult techniques and values are expressed against different standards. In any collection of data from laboratories with widely differing experience and technical skill there may be a few spurious results which upset correlations. This doubt will be answered only when the larger centres have collected enough pairs of sera and amniotic fluid from pregnancies where the fetus
methodological problems.
has
a
neural-tube defect
laboratory correlations. On physiological grounds
to
produce individual
it
seems probable that for are two distinct passage of fetal AFP into the maternal circulation. The more general route is transplacental and accounts for the gradually rising concentration of maternal-serum AFP with the progression of pregnancy. It explains the increase in maternal AFP levels found in twin pregnancies, in threatened and spontaneous abortion, and associated with low birthweight and perinatal dearth. 16 The other route is trans-membrane and is relevant in those fetal conditions where there is an associated raised amniotic-fluid AFP concentration. Though the two routes are not mutually exclusive many complications of pregnancy can be interpreted in terms of one or the other. Such a hypothesis has obvious implications for policies of maternal-serum AFP screening. Since transplacental AFP passage is likely to be a frequent event, most high maternal-serum AFP values will not signify a neural-tube defect or any other fetal condition in which amniotic-fluid AFP is raised. Thus, there is little prospect that maternalserum AFP measurement will ever be improved to a point where it becomes a diagnostic method for neural tube defects. On the other hand, since both amniotic-fluid AFP and maternal-serum AFP are raised in most cases of neural-tube defect, use of these two measures as independent estimates of risk may not be justified.
there
routes
Medical Education: Enemy of the Good? THE role of doctors and medical
technology is a which evokes subject remarkably divergent views, even within the medical profession. Some clinicians, recalling a lifetime’s experience with individual patients or in medical research, hold that the highest standards must at all costs be maintained in clinical practice and research. Disease 16. Brock DJH, Barron L, Duncan P, elevated mid-trimester maternal 1979; i: 1281-82.
Scrimgeour JB, Watt M. Significance of plasma-alpha-fetoprotein values. Lancet
arises in the individual, and it is with individuals that the profession has traditionally dealt. Through the doctor-patient relationship and through centres of excellence of treatment, research, and teaching, the sick are cured, medical science is advanced, and doctors are trained. And so it should remain, in developing as in developed countries; the exigencies of spreading rural health care with a preventive bias should not be allowed to dilute clinical standards at the centre.I At the other extreme are those who hold that the medical profession has greatly overreached itself: the efficacy of many treatments is grossly overestimated ; the profession exaggerates its role as a determinant of health and so reinforces a morbid society; it creates iatrogenic diseases; it mystifies the population with its technology, "medicalising" life and creating dependence and passivity; it thus undermines the individual’s and community’s ability to shape their physical and social environment and expropriates their capacity for health promotion and self-care. "The medical establishment has become a major threat to health."2 Such absolute statements pose the problem incorrectly. It is not a question of absolute quality or mere quantity, of clinical excellence or rural prevention, of doctors or lower-level health workers, of professional workers or community involvement. The challenge is to find the right mix of these components which is appropriate in content and form to a country’s health and social conditions, and which is capable of being distributed according to priority needs. This is at the essence of the World Health Organisation’s policy. of primary health care3 (applicable in its general form to developed and developing countries alike). But such a mix cannot be found by guesswork or intuition derived from clinical experience. It requires a scientific
approach. Health care is not (directly) productive of material wealth. On the contrary it is a drain on resources and the amount that any country can spend on health is limited. We must therefore seek value for money,4 and this entails hard-headed medical auditing. In the cost-effectiveness exercise there can be no sacred cow of clinical excellence or we fall into a trap of medieval a-priorism: clinical excellence is necessary because it is excellent. Professional clinical care must be assessed in cost-effectiveness terms for its overall impact on the health of thepopulation, alongside that of (a very much larger number of cheaper) primary health-care workers, promotive and preventive activities, and of doctors and delivery of health care in developing Lancet 1979; ii: 297-99. 2. Illich I. Medical nemesis. London: Calder & Boyars, 1975. 3. Primary health care: a joint report by the Director-General of the World Health Organisation and the Executive Director of the United Nations Children’s Fund. Geneva, 1978. 4. Abel-Smith B. Value for money in health services. London: Heinemann, 1976. 1. Cook GC.
Training
countries.
1001
expenditure outside the health-care sector (on nutrition, housing, sanitation, employment, production, safety at work, and so on). By diverting even
the best can become the enemy of the good. We cannot fix clinical excellence as an absolute and then see what can be done with the leavings, because along with clinical excellence go the immense economic burden of proliferating medical technology, a top-heavy manpower structure, the centralisation of resources in a few (urban) centres, and a curative bias-precisely the problems to be overcome in health care in developing countries resources
today/s The issue is about the alternative use of resources, based on what economists call opportunity cost. We have to balance the great cost of reaching the last peaks of medical excellence against use of the same resources in a different and more distributive way. Medical standards should be as high as can be attained within a health care programme rationally composed and equitably distributed. This principle applies in developed countries6 and with even more urgency in developing countries. It is also at the essence of the type of doctors which should be trained and in what environment they should be taught. It would be quite inappropriate to train doctors primarily as clinicians in palaces of technology if most doctors would subsequently be practising in small units with modest facilities. If traditional medical education is largely inappropriate in developed countries,how much more so is it in the conditions of underdevelopment. The needs of teaching are no argument against a cost-effectiveness approach. On the contrary, the training must reinforce such an approach; doctors should be excellently trained in an atmosphere of social and clinical reality. How has the traditional notion of absolute clinical excellence arisen, independent of questions of cost-effectiveness and health-care distribution? The medical profession evolved on the basis of private practice, in which the doctors saw those patients wealthy enough to foot the bill. The doctor could then (within reason) free his mind from costs; it was the patient’s problem. This ethic has been carried over by professionals working in national health services, where it is the State that foots the bill. The cost-effectiveness approach has hardly penetrated medical education and practice. However, when plans are drawn up for the health of a whole country, it is the people who will foot the bill, and their aim will be to secure a maximum return in health. 5. Office of Health Economics. Medical care in developing countries. London: Office of Health Economics, 1972. 6. Sharing resources for health in England. Department of Health and Social Security. London: HM Stationery Office, 1976. 7. Organisation for Economic Co-operation and Development. New directions in education for changing health care systems. Paris: OECD Publications, 1975.
MS AND EAE MULTIPLE sclerosis (MS) affects young adults and is thought to result from an immune process in genetically susceptible individuals, induced in childhood by something in the environment. The essential feature is a tendency to spontaneous relapses and remissions; demyelination is not specific to MS. Work on the pathogenesis has been handicapped by the unavailability of central-nervous-system (CNS) tissue in the active stages. An experimental model of the disease is therefore desirable, and merits and demerits of experimental allergic encephalomyelitis (EAE) in this context were discussed at a symposium organised by the MS Society of Great Britain and Northern Ireland and dedicated to the memory of Dr L. A. Liversedge.1 EAE can be induced in various species by peripheral immunisation with the CNS antigen, myelin basic protein (MBP), in complete Freund’s adjuvant. The illness is usually monophasic, leading to death, and is characterised by inflammation of the CNS. A relapsing and
remitting form of EAE, first described thirty years ago, is produced by minor alterations in the inoculum and the experimental protocol. 2-5 MS and EAE have much in common apart from their clinical similarities. Firstly, the induction of relapsing EAE requires immunisation of juvenile animals, and strains within species show differences in susceptibility.3-5 In EAE susceptibility may, in part, be histocompatibility-linked.6 Both these findings are analogous to the results of epidemiologicaF and histocompatibility8 studies in MS. Secondly, the natural history of relapsing EAE is as variable between animals as is the clinical course of MS, and in both diseases the pathological changes are more extensive than suggested by the clinical illness. Thirdly, a spectrum of abnormality is seen in both diseases; the early inflammatory changes develop, in relapses, into demyelination and sclerosis.9 Plaques of varying age have a perivascular distribution and show evidence of remyelination.9.1o. Fourthly, in both diseases there is production of immunoglobulin (IgG) within the CNS which is demonstrable within plaquesll.12 and in
AN, Cuzner ML, eds. The suppression of multiple sclerosis and experimental allergic encephalomyelitis. London: Academic Press (in
1. Davison
press). 2. Ferraro A, Cazzullo CL. Chronic experimental allergic encephalomyelitis in monkeys. J Neuropath Exp Neurol 1948; 7: 235-60. 3. McFarlin DE, Blank SE, Kibler RF. Recurrent experimental allergic encephalomyelitis in the Lewis rat. J Immunol 1974; 113: 712-15. 4. Snyder DH, Valsamis MP, Stone SH, Raine CS. Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomye-
litis. J Neuropath Exp Neurol 1975; 34: 209-21. HM, Keith AB. Chronic relapsing experimental allergic encephalomyelitis; an experimental model of multiple sclerosis. Ann Neurol 1977;
5. Wisniewski
1: 144-48. 6. Alvord EC. Genetic and environmental interactions determining susceptibility and resistance to experimental allergic encephalomyelitis: a review.
Acta Neurol Scand 1977; 55: Suppl. 63, 71-92. 7. Acheson ED. Epidemiology of multiple sclerosis. Br Med Bull 1977; 33: 9-14. 8. Batchelor JR, Compston DAS, McDonald WI. The significance of the association between HLA and multiple sclerosis. Br Med Bull 1978; 34: 279-84. 9. Lassman H, Wisniewski HM. Chronic relapsing experimental allergic encephalomyelitis. Arch Neurol 1979; 36: 490-97. 10. Prineas JA, Connell F. Remyelination in multiple sclerosis. Ann Neurol
1979; 5: 22-31. 11. Esiri MM.
Immunoglobulin containing cells in multiple sclerosis plaques. Lancet 1977; ii: 478-80. 12. Paterson PY. The immunopathology of experimental allergic encephalomyelitis. In: Davison AN, Cuzner ML, eds. The suppression of multiple sclerosis and experimental allergic encephalomyelitis. London: Academic Press (in press).
The absence of a strong correlation in the data of the collaborative study5 may be the result of In many centres maternal-serum AFP and amniotic-fluid AFP are measured by difficult techniques and values are expressed against different standards. In any collection of data from laboratories with widely differing experience and technical skill there may be a few spurious results which upset correlations. This doubt will be answered only when the larger centres have collected enough pairs of sera and amniotic fluid from pregnancies where the fetus
methodological problems.
has
a
neural-tube defect
laboratory correlations. On physiological grounds
to
produce individual
it
seems probable that for are two distinct passage of fetal AFP into the maternal circulation. The more general route is transplacental and accounts for the gradually rising concentration of maternal-serum AFP with the progression of pregnancy. It explains the increase in maternal AFP levels found in twin pregnancies, in threatened and spontaneous abortion, and associated with low birthweight and perinatal dearth. 16 The other route is trans-membrane and is relevant in those fetal conditions where there is an associated raised amniotic-fluid AFP concentration. Though the two routes are not mutually exclusive many complications of pregnancy can be interpreted in terms of one or the other. Such a hypothesis has obvious implications for policies of maternal-serum AFP screening. Since transplacental AFP passage is likely to be a frequent event, most high maternal-serum AFP values will not signify a neural-tube defect or any other fetal condition in which amniotic-fluid AFP is raised. Thus, there is little prospect that maternalserum AFP measurement will ever be improved to a point where it becomes a diagnostic method for neural tube defects. On the other hand, since both amniotic-fluid AFP and maternal-serum AFP are raised in most cases of neural-tube defect, use of these two measures as independent estimates of risk may not be justified.
there
routes
Medical Education: Enemy of the Good? THE role of doctors and medical
technology is a which evokes subject remarkably divergent views, even within the medical profession. Some clinicians, recalling a lifetime’s experience with individual patients or in medical research, hold that the highest standards must at all costs be maintained in clinical practice and research. Disease 16. Brock DJH, Barron L, Duncan P, elevated mid-trimester maternal 1979; i: 1281-82.
Scrimgeour JB, Watt M. Significance of plasma-alpha-fetoprotein values. Lancet
arises in the individual, and it is with individuals that the profession has traditionally dealt. Through the doctor-patient relationship and through centres of excellence of treatment, research, and teaching, the sick are cured, medical science is advanced, and doctors are trained. And so it should remain, in developing as in developed countries; the exigencies of spreading rural health care with a preventive bias should not be allowed to dilute clinical standards at the centre.I At the other extreme are those who hold that the medical profession has greatly overreached itself: the efficacy of many treatments is grossly overestimated ; the profession exaggerates its role as a determinant of health and so reinforces a morbid society; it creates iatrogenic diseases; it mystifies the population with its technology, "medicalising" life and creating dependence and passivity; it thus undermines the individual’s and community’s ability to shape their physical and social environment and expropriates their capacity for health promotion and self-care. "The medical establishment has become a major threat to health."2 Such absolute statements pose the problem incorrectly. It is not a question of absolute quality or mere quantity, of clinical excellence or rural prevention, of doctors or lower-level health workers, of professional workers or community involvement. The challenge is to find the right mix of these components which is appropriate in content and form to a country’s health and social conditions, and which is capable of being distributed according to priority needs. This is at the essence of the World Health Organisation’s policy. of primary health care3 (applicable in its general form to developed and developing countries alike). But such a mix cannot be found by guesswork or intuition derived from clinical experience. It requires a scientific
approach. Health care is not (directly) productive of material wealth. On the contrary it is a drain on resources and the amount that any country can spend on health is limited. We must therefore seek value for money,4 and this entails hard-headed medical auditing. In the cost-effectiveness exercise there can be no sacred cow of clinical excellence or we fall into a trap of medieval a-priorism: clinical excellence is necessary because it is excellent. Professional clinical care must be assessed in cost-effectiveness terms for its overall impact on the health of thepopulation, alongside that of (a very much larger number of cheaper) primary health-care workers, promotive and preventive activities, and of doctors and delivery of health care in developing Lancet 1979; ii: 297-99. 2. Illich I. Medical nemesis. London: Calder & Boyars, 1975. 3. Primary health care: a joint report by the Director-General of the World Health Organisation and the Executive Director of the United Nations Children’s Fund. Geneva, 1978. 4. Abel-Smith B. Value for money in health services. London: Heinemann, 1976. 1. Cook GC.
Training
countries.
1001
expenditure outside the health-care sector (on nutrition, housing, sanitation, employment, production, safety at work, and so on). By diverting even
the best can become the enemy of the good. We cannot fix clinical excellence as an absolute and then see what can be done with the leavings, because along with clinical excellence go the immense economic burden of proliferating medical technology, a top-heavy manpower structure, the centralisation of resources in a few (urban) centres, and a curative bias-precisely the problems to be overcome in health care in developing countries resources
today/s The issue is about the alternative use of resources, based on what economists call opportunity cost. We have to balance the great cost of reaching the last peaks of medical excellence against use of the same resources in a different and more distributive way. Medical standards should be as high as can be attained within a health care programme rationally composed and equitably distributed. This principle applies in developed countries6 and with even more urgency in developing countries. It is also at the essence of the type of doctors which should be trained and in what environment they should be taught. It would be quite inappropriate to train doctors primarily as clinicians in palaces of technology if most doctors would subsequently be practising in small units with modest facilities. If traditional medical education is largely inappropriate in developed countries,how much more so is it in the conditions of underdevelopment. The needs of teaching are no argument against a cost-effectiveness approach. On the contrary, the training must reinforce such an approach; doctors should be excellently trained in an atmosphere of social and clinical reality. How has the traditional notion of absolute clinical excellence arisen, independent of questions of cost-effectiveness and health-care distribution? The medical profession evolved on the basis of private practice, in which the doctors saw those patients wealthy enough to foot the bill. The doctor could then (within reason) free his mind from costs; it was the patient’s problem. This ethic has been carried over by professionals working in national health services, where it is the State that foots the bill. The cost-effectiveness approach has hardly penetrated medical education and practice. However, when plans are drawn up for the health of a whole country, it is the people who will foot the bill, and their aim will be to secure a maximum return in health. 5. Office of Health Economics. Medical care in developing countries. London: Office of Health Economics, 1972. 6. Sharing resources for health in England. Department of Health and Social Security. London: HM Stationery Office, 1976. 7. Organisation for Economic Co-operation and Development. New directions in education for changing health care systems. Paris: OECD Publications, 1975.
MS AND EAE MULTIPLE sclerosis (MS) affects young adults and is thought to result from an immune process in genetically susceptible individuals, induced in childhood by something in the environment. The essential feature is a tendency to spontaneous relapses and remissions; demyelination is not specific to MS. Work on the pathogenesis has been handicapped by the unavailability of central-nervous-system (CNS) tissue in the active stages. An experimental model of the disease is therefore desirable, and merits and demerits of experimental allergic encephalomyelitis (EAE) in this context were discussed at a symposium organised by the MS Society of Great Britain and Northern Ireland and dedicated to the memory of Dr L. A. Liversedge.1 EAE can be induced in various species by peripheral immunisation with the CNS antigen, myelin basic protein (MBP), in complete Freund’s adjuvant. The illness is usually monophasic, leading to death, and is characterised by inflammation of the CNS. A relapsing and
remitting form of EAE, first described thirty years ago, is produced by minor alterations in the inoculum and the experimental protocol. 2-5 MS and EAE have much in common apart from their clinical similarities. Firstly, the induction of relapsing EAE requires immunisation of juvenile animals, and strains within species show differences in susceptibility.3-5 In EAE susceptibility may, in part, be histocompatibility-linked.6 Both these findings are analogous to the results of epidemiologicaF and histocompatibility8 studies in MS. Secondly, the natural history of relapsing EAE is as variable between animals as is the clinical course of MS, and in both diseases the pathological changes are more extensive than suggested by the clinical illness. Thirdly, a spectrum of abnormality is seen in both diseases; the early inflammatory changes develop, in relapses, into demyelination and sclerosis.9 Plaques of varying age have a perivascular distribution and show evidence of remyelination.9.1o. Fourthly, in both diseases there is production of immunoglobulin (IgG) within the CNS which is demonstrable within plaquesll.12 and in
AN, Cuzner ML, eds. The suppression of multiple sclerosis and experimental allergic encephalomyelitis. London: Academic Press (in
1. Davison
press). 2. Ferraro A, Cazzullo CL. Chronic experimental allergic encephalomyelitis in monkeys. J Neuropath Exp Neurol 1948; 7: 235-60. 3. McFarlin DE, Blank SE, Kibler RF. Recurrent experimental allergic encephalomyelitis in the Lewis rat. J Immunol 1974; 113: 712-15. 4. Snyder DH, Valsamis MP, Stone SH, Raine CS. Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomye-
litis. J Neuropath Exp Neurol 1975; 34: 209-21. HM, Keith AB. Chronic relapsing experimental allergic encephalomyelitis; an experimental model of multiple sclerosis. Ann Neurol 1977;
5. Wisniewski
1: 144-48. 6. Alvord EC. Genetic and environmental interactions determining susceptibility and resistance to experimental allergic encephalomyelitis: a review.
Acta Neurol Scand 1977; 55: Suppl. 63, 71-92. 7. Acheson ED. Epidemiology of multiple sclerosis. Br Med Bull 1977; 33: 9-14. 8. Batchelor JR, Compston DAS, McDonald WI. The significance of the association between HLA and multiple sclerosis. Br Med Bull 1978; 34: 279-84. 9. Lassman H, Wisniewski HM. Chronic relapsing experimental allergic encephalomyelitis. Arch Neurol 1979; 36: 490-97. 10. Prineas JA, Connell F. Remyelination in multiple sclerosis. Ann Neurol
1979; 5: 22-31. 11. Esiri MM.
Immunoglobulin containing cells in multiple sclerosis plaques. Lancet 1977; ii: 478-80. 12. Paterson PY. The immunopathology of experimental allergic encephalomyelitis. In: Davison AN, Cuzner ML, eds. The suppression of multiple sclerosis and experimental allergic encephalomyelitis. London: Academic Press (in press).
