- Email: [email protected]
ANOTHER KIND OF MEASLES ENCEPHALITIS?
552 the breast was noticed, most of these 17 women displayed an aberration of hormone excretion which would have served to reveal them as a susceptible section of the population. Earlier surveys might have led these workers to expect that if these 17 women differed from the normal it would be that they excreted less Eetiocholanolone and more 17-hydroxycorticosteroid; and, indeed, this was what was found in some cases. What was more significant, however, was that the levels of these substances in the urine of these women deviated from the mean in other directions-the aberration, that is to say, was multidirectional. By a sophisticated statistical technique it was possible, from a study of the original urine samples, to separate a population with 1-65 times the normal expectancy for cancer of the breast from the remainder who had only 0-35 times the chances of getting the disease compared with the normal probability. Taking a different standard of aberration of hormone excretion, it was possible to pick out the 20% who had between two and three times the normal probability of mammary
authorities have abandoned their risk register, while others have been discouraged from beginning one. Nevertheless, the concept is a useful one and ought to be rescued. Opp62 has reviewed the present situation, and his practical suggestions, if adopted, might well salvage both the registers and the sanity of those who operate them. He proposes a short list of criteria for admission to the register, which would probably include 15-20% of all infants. The list comprises hereditary deafness, maternal rubella, short gestation and/or low birth-weight, moderate or severe asphyxia, and neonatal factors (feeding difficulties, poor weight-gain, convulsions, cyanotic or apnoeic attacks, abnormal neurological signs, and hyperbilirubinaemia). Oppe pleads for definition of as many as possible of these conditions in order to permit valid comparisons. Risk registers have been allowed to grow so large that they overwhelm their makers. The way is now clear for clinicians and medical administrators to regain the mastery of this valuable weapon in the fight for health.
cancer.
If the value of research lies in the fresh questions that the outcome poses, then this research is valuable indeed. Much of the complexity of the situation might have been resolved if the urinary abnormalities in patients with breast cancer had all been in the same direction, but, so far as the investigation has gone, this has not been so. All this implies that Dr. Bulbrook and Mr. Hayward have revealed by their unique investigation that the underlying factors in the generation of breast cancer are even more complex than we had assumed. More important, however, they have shown how at least one aspect of this complex picture may be surveyed, and information of fundamental biological significance may emerge from this survey. The ability to recognise a group within the general population with a greater proclivity to the disease holds out the hope that special care for such women and the use of the modern methods of diagnosis, such as soft-tissue radiography and thermography, may reveal cancer of the breast before a lump is clinically obvious and when the chances of a cure by orthodox means are excellent.
ANOTHER KIND OF MEASLES ENCEPHALITIS?
THE
condition known as subacute sclerosing panencephalitis or leucoencephalitis (and also as subacute inclusion-body encephalitis) affects children and adolescents, and it usually progresses from an insidious onset with psychic changes, through involuntary spasmodic movements and increasing mental deterioration, to rare
to six months after the first the brain shows perivascular Examination of symptoms.3 infiltration of plasma cells and lymphocytes, hypertrophy of astrocytes, microglial proliferation, and destruction of myelinated axons. The finding of intranuclear and intracytoplasmic inclusions, similar to those seen in some virus infections, supports the idea that this disease too is due to a virus. The demonstration of virus-like particles in brain sections examined in the electron microscope has further strengthened this view.4-6 Though no virus has yet been isolated, evidence suggesting that measles virus may in fact cause this disease is presented by Dr. Connolly and his colleagues on p. 542. Although measles usually produces only a mild illness in childhood, electroencephalography has shown that the brain is affected in a high proportion of children who do RISK REGISTERS not have clinical encephalitis.7 Most children recover fully FOR some handicaps the chances of successful treatment after an attack of measles, but an important minority have some permanent disability, either physical or mental.a are much improved if they can be detected before symptoms are noticeable. Many can be recognised by Acute encephalitis following measles is generally held to be a manifestation of allergy, and not the result of multiclinical examination: others require laboratory tests. Ideally, all infants should be screened for all defects which plication of virus in brain cells.9 If subacute sclerosing require presymptomatic treatment; but screening pro- leucoencephalitis is in fact established to be a late result of measles, then it must be assumed that virus persists in grammes are often limited by shortage of money and some cells in the brain, to emerge and multiply again after manpower, which therefore dictate a selection procedure. As a basis for selection, Sheridan1 evolved the concept of an interval of months or years. Chronic carrier states are the child " at risk". The child at risk-or, more known in human infections with herpes-simplex virus, accurately, at increased risk-is one who, as a result of and virus carrier states have been identified in a number one or more adverse genetic or environmental influences, of animal and tissue-culture systems. Work on the is more likely than most to have a physical or mental 2. Oppé, T. E. Devl. Med. Child Neurol. 1967, 9, 13. 3. van Bogaert, L. J. Neurol. Neurosurg. Psychiat. 1945, 8, 101. handicap. These influences include hereditary factors, 4. Gonatas, N. K., Shy, G. M. Nature, Lond. 1965, 208, 1338. difficulties at and prenatal disorders, birth, prematurity, 5. Bouteille, M., Fontaine, C., Vedrenne, C., Delarue, J. Rev. Neurol. some neonatal disturbances of health. Sheridan’s list of 1965, 113, 454. 6. Tellez-Nagel, I., Harter, D. H. Science, N.Y. 1966, 154, 899. criteria for placing an infant " at risk " was so com7. Gibbs, F. A., Gibbs, E. L., Carpenter, P. R., Spies, H. W. J. Am. med. Ass. 1959, 171, 1050. prehensive that many local authorities found 50% or more 8. Miller, D. L. Br. med. J. 1964, ii, 75. of all babies eligible for inclusion. Consequently, some
end in death six weeks
9.
1. Sheridan, M. D. Mon. Bull. Min. Hlth, 1962,
21, 238.
Katz, S. L., Enders, J. F. in Viral and Rickettsial Infections of Man (edited by F. L. Horsfall and I. Tamm); p. 784. London, 1965.
553
of measles virus in cells cultured with and without measles antiserum showed that virus was easily recovered from the carrier culture grown without antiserum, but no infectious virus was obtained from cells grown in the presence of antiserum, although measles antigen was readily detected under these conditions.10 It may be very hard to try to cultivate a virus from the brains of patients who have died of subacute sclerosing leucoencephalitis, but further attempts must clearly be made.
persistence
THE HANDICAPPED CHILD AT SCHOOL
OVER the years the pattern of physical handicap in children has changed greatly. According to the latest report 11 from the Department of Education and Science, the main causes of severe physical disability among children in special schools are now hereditary or congenital, and relatively few children attend these schools because of rheumatic heart-disease, osteomyelitis, or tuberculosis. Whereas the number affected by residual paralysis from poliomyelitis has fallen dramatically, more and more children with spina bifida are now surviving as a result of skilled surgery and control of infection in the first few days of life. The changing prevalence of disabling diseases calls for a reassessment of the educational facilities for handicapped children-the more so because the prevalence of individual diseases appears to vary widely from region to region. An epidemiological basis for the differences is improbable: a much more likely explanation is that lack of special schools or classes leads to a lower ascertainment-rate in some areas. Some would argue that the present emphasis upon the need for special schools is misguided. Since not all children with spina bifida can be accommodated in special schools, would it not be wiser to devote more effort to placing them in local schools, as Eckstein and Macnab ]2 suggest ? On the other hand, it would be unwise to follow such a dictum blindly, as some social workers have been ready to do. In haemophilia, for example, a residential special school would have advantages in that children could be treated without interrupting their education.13 It is interesting to note that the parents of many " thalidomide " children have asked for their children to be educated in ordinary schools. There are, however, many practical difficulties for the handicapped child who attends a local primary school. Classes are usually large, facilities may be inconvenient, overprotective attitudes by parents may make excessive demands upon teachers, and the provision of even minor medical or nursing care may be impossible. Even travelling to and from school may create problems. The attitude of the other children must also be considered, for they can sometimes be extremely cruel to a handicapped child. The parents’ reluctance to agree to special educational facilities may be a symptom of a more general failure to accept the implications of their child’s handicap. In such circumstances the doctor’s assurance that the standard of education is satisfactory will be a valuable compensation. The introduction of the Certificate of Secondary Education has provided a tremendous impetus for special schools to 10. Rustigian, R. J. Bact. 1966, 92, 1792, 1805. 11. The Health of the School Child 1964 & 1965. Report of the Chief Medical Officer of the Department of Education and Science. H.M. Stationery Office, 1966. Pp. 153. 12s. 6d. 12. Eckstein, H. B., Macnab, G. H. Lancet, 1966, i, 842. 13. Britten, M. I., Spooner, R. J. D., Dormandy, K. M., Biggs, R. Br. med. J. 1966, ii, 224.
offer improved educational opportunities. It should be remembered that many deaf children transferred to ordinary schools fail to achieve their expected academic potential. 14 Moreover frequent short absences from ordinary primary schools impair educational performance,15 and such absences will be more likely in a handicapped child. The problems of the handicapped child do not cease when he leaves school, and a working-party 16 concluded that there should be a functional assessment of all physically disabled school-leavers to help the youth employment service in finding suitable work for them. Following these recommendations, the Department of Education and Science has prepared a draft medical report form for this purpose. Ideally, the school health service should assume responsibility for the care of the young handicapped school leaver in his early years in industry.
CENTRAL ACTION OF CHLORPROMAZINE
CHLORPROMAZINE, like several other centrally acting drugs, has many pharmacological actions, depending on the experimental situation in which it is tested. Thus, Courvoisier and her colleagues" described ganglionblocking, antiadrenaline, antihistamine, antifibrillatory, antipyretic, anticonvulsant, and antiemetic actions. They also showed that chlorpromazine enhanced the potency of analgesic and central-depressant drugs. Its most important application in clinical practice is as a tranquilliser, and the mechanism of this action has been the subject of much experimental work. Das et al.l8 found that chlorpromazine depressed electrically induced sham rage in decorticate cats, and that in the rhesus monkey it produced electroencephalographic changes similar to those obtained by interrupting the ascending pathways from the reticular formation concerned with arousal and wakefulness. This was confirmed by Bradley and Hance, 19 who found that chlorpromazine produced slow waves at 1 or 2 cycles per second in all regions of the brain of the conscious cat, associated with motor retardation and apparent indifference to sensory stimuli. Work with intact, spinal, and decerebrate animals 20-23 also suggested that its main sites of action were receptors in the brainstem reticular formation or pathways leading to and from this system. Bradley believes that chlorpromazine has a selective action on the sensory inflow into the reticular formation from afferent pathways, and he and his colleagues have investigated this action at the neuronal level. 24 Using micro-iontophoresis, they measured the effects of acetylcholine, noradrenaline, and 5-hydroxytryptamine on brain-stem neurones in the cat 25 and found 14.
Report on a survey of deaf children who have been transferred from special schools or units to ordinary schools. H.M. Stationery Office,
1963. 15. Douglas, J. W. B., Ross, J. M. Br. J. educ. Psychol. 1965, 35, 28. 16. The Handicapped School Leaver. British Council for Rehabilitation of the Disabled. London, 1964. 17. Courvoisier, S., Fournel, J., Ducrot, R., Kolsky, M., Koetshet, P. Archs. int. Pharmacodyn. Thér. 1953, 92, 305. 18. Das, N. N., Dasgupta, S. R., Werner, G. Bull. Calcutta Sch. trop. Med. Hyg. 1954, 1, 5. 19. Bradley, P. B., Hance, A. J. J. Physiol., Lond. 1955, 129, 50P. 20. Berger, F. M., Campbell, G. L., Hendley, C. D., Ludwig, B. J., Lynes, T. E. Ann. N.Y. Acad. Sci. 1957, 66, 686. 21. Bradley, P. B., Key, B. J. Br. J. Pharmac. Chemother. 1959, 14, 340. 22. Silvestrini, B., Mafii, G. J. Pharm. Pharmac. 1959, 11, 224. 23. Webster, R. A. Br. J. Pharmac. Chemother. 1962, 18, 150. 24. Bradley, P. B., Wolstencroft, J. H., Hösli, L., Avanzino, G. L. Nature, Lond. 1966, 212, 1425. 25. Bradley, P. B., Wolstencroft, J. H. Br. med. Bull. 1965, 21, 15.
authorities have abandoned their risk register, while others have been discouraged from beginning one. Nevertheless, the concept is a useful one and ought to be rescued. Opp62 has reviewed the present situation, and his practical suggestions, if adopted, might well salvage both the registers and the sanity of those who operate them. He proposes a short list of criteria for admission to the register, which would probably include 15-20% of all infants. The list comprises hereditary deafness, maternal rubella, short gestation and/or low birth-weight, moderate or severe asphyxia, and neonatal factors (feeding difficulties, poor weight-gain, convulsions, cyanotic or apnoeic attacks, abnormal neurological signs, and hyperbilirubinaemia). Oppe pleads for definition of as many as possible of these conditions in order to permit valid comparisons. Risk registers have been allowed to grow so large that they overwhelm their makers. The way is now clear for clinicians and medical administrators to regain the mastery of this valuable weapon in the fight for health.
cancer.
If the value of research lies in the fresh questions that the outcome poses, then this research is valuable indeed. Much of the complexity of the situation might have been resolved if the urinary abnormalities in patients with breast cancer had all been in the same direction, but, so far as the investigation has gone, this has not been so. All this implies that Dr. Bulbrook and Mr. Hayward have revealed by their unique investigation that the underlying factors in the generation of breast cancer are even more complex than we had assumed. More important, however, they have shown how at least one aspect of this complex picture may be surveyed, and information of fundamental biological significance may emerge from this survey. The ability to recognise a group within the general population with a greater proclivity to the disease holds out the hope that special care for such women and the use of the modern methods of diagnosis, such as soft-tissue radiography and thermography, may reveal cancer of the breast before a lump is clinically obvious and when the chances of a cure by orthodox means are excellent.
ANOTHER KIND OF MEASLES ENCEPHALITIS?
THE
condition known as subacute sclerosing panencephalitis or leucoencephalitis (and also as subacute inclusion-body encephalitis) affects children and adolescents, and it usually progresses from an insidious onset with psychic changes, through involuntary spasmodic movements and increasing mental deterioration, to rare
to six months after the first the brain shows perivascular Examination of symptoms.3 infiltration of plasma cells and lymphocytes, hypertrophy of astrocytes, microglial proliferation, and destruction of myelinated axons. The finding of intranuclear and intracytoplasmic inclusions, similar to those seen in some virus infections, supports the idea that this disease too is due to a virus. The demonstration of virus-like particles in brain sections examined in the electron microscope has further strengthened this view.4-6 Though no virus has yet been isolated, evidence suggesting that measles virus may in fact cause this disease is presented by Dr. Connolly and his colleagues on p. 542. Although measles usually produces only a mild illness in childhood, electroencephalography has shown that the brain is affected in a high proportion of children who do RISK REGISTERS not have clinical encephalitis.7 Most children recover fully FOR some handicaps the chances of successful treatment after an attack of measles, but an important minority have some permanent disability, either physical or mental.a are much improved if they can be detected before symptoms are noticeable. Many can be recognised by Acute encephalitis following measles is generally held to be a manifestation of allergy, and not the result of multiclinical examination: others require laboratory tests. Ideally, all infants should be screened for all defects which plication of virus in brain cells.9 If subacute sclerosing require presymptomatic treatment; but screening pro- leucoencephalitis is in fact established to be a late result of measles, then it must be assumed that virus persists in grammes are often limited by shortage of money and some cells in the brain, to emerge and multiply again after manpower, which therefore dictate a selection procedure. As a basis for selection, Sheridan1 evolved the concept of an interval of months or years. Chronic carrier states are the child " at risk". The child at risk-or, more known in human infections with herpes-simplex virus, accurately, at increased risk-is one who, as a result of and virus carrier states have been identified in a number one or more adverse genetic or environmental influences, of animal and tissue-culture systems. Work on the is more likely than most to have a physical or mental 2. Oppé, T. E. Devl. Med. Child Neurol. 1967, 9, 13. 3. van Bogaert, L. J. Neurol. Neurosurg. Psychiat. 1945, 8, 101. handicap. These influences include hereditary factors, 4. Gonatas, N. K., Shy, G. M. Nature, Lond. 1965, 208, 1338. difficulties at and prenatal disorders, birth, prematurity, 5. Bouteille, M., Fontaine, C., Vedrenne, C., Delarue, J. Rev. Neurol. some neonatal disturbances of health. Sheridan’s list of 1965, 113, 454. 6. Tellez-Nagel, I., Harter, D. H. Science, N.Y. 1966, 154, 899. criteria for placing an infant " at risk " was so com7. Gibbs, F. A., Gibbs, E. L., Carpenter, P. R., Spies, H. W. J. Am. med. Ass. 1959, 171, 1050. prehensive that many local authorities found 50% or more 8. Miller, D. L. Br. med. J. 1964, ii, 75. of all babies eligible for inclusion. Consequently, some
end in death six weeks
9.
1. Sheridan, M. D. Mon. Bull. Min. Hlth, 1962,
21, 238.
Katz, S. L., Enders, J. F. in Viral and Rickettsial Infections of Man (edited by F. L. Horsfall and I. Tamm); p. 784. London, 1965.
553
of measles virus in cells cultured with and without measles antiserum showed that virus was easily recovered from the carrier culture grown without antiserum, but no infectious virus was obtained from cells grown in the presence of antiserum, although measles antigen was readily detected under these conditions.10 It may be very hard to try to cultivate a virus from the brains of patients who have died of subacute sclerosing leucoencephalitis, but further attempts must clearly be made.
persistence
THE HANDICAPPED CHILD AT SCHOOL
OVER the years the pattern of physical handicap in children has changed greatly. According to the latest report 11 from the Department of Education and Science, the main causes of severe physical disability among children in special schools are now hereditary or congenital, and relatively few children attend these schools because of rheumatic heart-disease, osteomyelitis, or tuberculosis. Whereas the number affected by residual paralysis from poliomyelitis has fallen dramatically, more and more children with spina bifida are now surviving as a result of skilled surgery and control of infection in the first few days of life. The changing prevalence of disabling diseases calls for a reassessment of the educational facilities for handicapped children-the more so because the prevalence of individual diseases appears to vary widely from region to region. An epidemiological basis for the differences is improbable: a much more likely explanation is that lack of special schools or classes leads to a lower ascertainment-rate in some areas. Some would argue that the present emphasis upon the need for special schools is misguided. Since not all children with spina bifida can be accommodated in special schools, would it not be wiser to devote more effort to placing them in local schools, as Eckstein and Macnab ]2 suggest ? On the other hand, it would be unwise to follow such a dictum blindly, as some social workers have been ready to do. In haemophilia, for example, a residential special school would have advantages in that children could be treated without interrupting their education.13 It is interesting to note that the parents of many " thalidomide " children have asked for their children to be educated in ordinary schools. There are, however, many practical difficulties for the handicapped child who attends a local primary school. Classes are usually large, facilities may be inconvenient, overprotective attitudes by parents may make excessive demands upon teachers, and the provision of even minor medical or nursing care may be impossible. Even travelling to and from school may create problems. The attitude of the other children must also be considered, for they can sometimes be extremely cruel to a handicapped child. The parents’ reluctance to agree to special educational facilities may be a symptom of a more general failure to accept the implications of their child’s handicap. In such circumstances the doctor’s assurance that the standard of education is satisfactory will be a valuable compensation. The introduction of the Certificate of Secondary Education has provided a tremendous impetus for special schools to 10. Rustigian, R. J. Bact. 1966, 92, 1792, 1805. 11. The Health of the School Child 1964 & 1965. Report of the Chief Medical Officer of the Department of Education and Science. H.M. Stationery Office, 1966. Pp. 153. 12s. 6d. 12. Eckstein, H. B., Macnab, G. H. Lancet, 1966, i, 842. 13. Britten, M. I., Spooner, R. J. D., Dormandy, K. M., Biggs, R. Br. med. J. 1966, ii, 224.
offer improved educational opportunities. It should be remembered that many deaf children transferred to ordinary schools fail to achieve their expected academic potential. 14 Moreover frequent short absences from ordinary primary schools impair educational performance,15 and such absences will be more likely in a handicapped child. The problems of the handicapped child do not cease when he leaves school, and a working-party 16 concluded that there should be a functional assessment of all physically disabled school-leavers to help the youth employment service in finding suitable work for them. Following these recommendations, the Department of Education and Science has prepared a draft medical report form for this purpose. Ideally, the school health service should assume responsibility for the care of the young handicapped school leaver in his early years in industry.
CENTRAL ACTION OF CHLORPROMAZINE
CHLORPROMAZINE, like several other centrally acting drugs, has many pharmacological actions, depending on the experimental situation in which it is tested. Thus, Courvoisier and her colleagues" described ganglionblocking, antiadrenaline, antihistamine, antifibrillatory, antipyretic, anticonvulsant, and antiemetic actions. They also showed that chlorpromazine enhanced the potency of analgesic and central-depressant drugs. Its most important application in clinical practice is as a tranquilliser, and the mechanism of this action has been the subject of much experimental work. Das et al.l8 found that chlorpromazine depressed electrically induced sham rage in decorticate cats, and that in the rhesus monkey it produced electroencephalographic changes similar to those obtained by interrupting the ascending pathways from the reticular formation concerned with arousal and wakefulness. This was confirmed by Bradley and Hance, 19 who found that chlorpromazine produced slow waves at 1 or 2 cycles per second in all regions of the brain of the conscious cat, associated with motor retardation and apparent indifference to sensory stimuli. Work with intact, spinal, and decerebrate animals 20-23 also suggested that its main sites of action were receptors in the brainstem reticular formation or pathways leading to and from this system. Bradley believes that chlorpromazine has a selective action on the sensory inflow into the reticular formation from afferent pathways, and he and his colleagues have investigated this action at the neuronal level. 24 Using micro-iontophoresis, they measured the effects of acetylcholine, noradrenaline, and 5-hydroxytryptamine on brain-stem neurones in the cat 25 and found 14.
Report on a survey of deaf children who have been transferred from special schools or units to ordinary schools. H.M. Stationery Office,
1963. 15. Douglas, J. W. B., Ross, J. M. Br. J. educ. Psychol. 1965, 35, 28. 16. The Handicapped School Leaver. British Council for Rehabilitation of the Disabled. London, 1964. 17. Courvoisier, S., Fournel, J., Ducrot, R., Kolsky, M., Koetshet, P. Archs. int. Pharmacodyn. Thér. 1953, 92, 305. 18. Das, N. N., Dasgupta, S. R., Werner, G. Bull. Calcutta Sch. trop. Med. Hyg. 1954, 1, 5. 19. Bradley, P. B., Hance, A. J. J. Physiol., Lond. 1955, 129, 50P. 20. Berger, F. M., Campbell, G. L., Hendley, C. D., Ludwig, B. J., Lynes, T. E. Ann. N.Y. Acad. Sci. 1957, 66, 686. 21. Bradley, P. B., Key, B. J. Br. J. Pharmac. Chemother. 1959, 14, 340. 22. Silvestrini, B., Mafii, G. J. Pharm. Pharmac. 1959, 11, 224. 23. Webster, R. A. Br. J. Pharmac. Chemother. 1962, 18, 150. 24. Bradley, P. B., Wolstencroft, J. H., Hösli, L., Avanzino, G. L. Nature, Lond. 1966, 212, 1425. 25. Bradley, P. B., Wolstencroft, J. H. Br. med. Bull. 1965, 21, 15.