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NEONATAL MYOCARDITIS
949
min simply reflects some underlying defect which also leads to accumulation of copper in the body tissues, it is difficult to see what might be gained by raising the level of cseruloplasmin artificially; but this certainly should be tried. NEONATAL MYOCARDITIS
WHILE investigating an outbreak of poliomyelitis in the village of Coxsackie, Dalldorf and Sickles1 isolated a hitherto unrecognised filterable agent from the fasces of two children with lower limb paralysis. Attempts to isolate the virus in rhesus monkeys were unsuccessful, but paralysis was induced in newborn suckling mice. This discovery heralded the advent of a new family of viruses, which are now recognised as responsible for such infections as Bornholm disease and herpangina, and also for some epidemics of aseptic meningitis and of neonatal myocarditis. During an epidemic of Summer-grippe in adults in Amsterdam in 1955 23 four fatal cases of myocarditis were observed in newborns. The diagnosis was suggested by a preceding febrile illness in three mothers, followed by the onset in their infants of dyspnoea, cyanosis, or pallor; in two instances there were electrocardiographic abnormalities. Necropsy revealed diffuse interstitial myocarditis, and in all instances Coxsackie virus group B, type 4, was isolated from the heart-muscle. The strain of virus involving the myocardium was similar to non-myocardial strains obtained at the same time from patients with pleurodynia and aseptic meningitis. Whereas the virus produced fever and transient virasmia in two six-month-old monkeys, it caused fatal myocarditis in a two-day-old monkey. Reports from other countries have also implicated the Coxsackie virus as the cause of neonatal myocarditisnone more convincingly than those from South Africa, which has had maternity-home epidemics in Johannesburg in 1952/ in nearby Southern Rhodesia in 1954,5 and in Cape Town in 1957.6-9 The onset of illness in the Cape Town maternityhome epidemic in April and June, 1957, was marked by fever, cyanosis, red throat, limpness, vomiting, and dyspnoea in European infants aged 5-8 days. Disproportionate tachycardia, triple rhythm, and a widespread precordial systolic murmur denoted severe infection, while hepatomegaly due to cardiac failure was of grave prognostic import. Changes consistent with seen in were myocarditis electrocardiographs of each of five infants in whom this examination was made; and the tracings subsequently returned to normal in the four survivors. A group-B, type-3 Coxsackie virus was isolated from the faeces of four who recovered and from the heart of four who died. There appeared to be a clear relation between the duration of illness, the acuteness of the myocardial lesion, and the concentration of virus in the heart-muscle. In an infant who died after 2 days’ illness there was acute myocarditis and the myocardial virus titre was very high. At the other extreme, the heart of an infant who died after 11 days’ illness showed evidence of tissue repair and the myocardial virus titre was low. This epidemic occurred at a time when Coxsackie1. Dalldorf, G., Sickles, G. M. Science, 1948, 108, 61. 2. Van Creveld, S., De Jager, H. Ann. pœdiat., Basle. 1956, 187, 100. 3. Verlinde, J. D., van Tongeren, H. A. E., Kret, A. ibid. p. 113. 4. Javett, S. N. Heymann, S., Mundel, B., Pepler, W. J., Lurie, H. I., Gear, J. H. S., Measroch, V., Kirsch, Z. J. Pediat. 1956, 48, 1. 5. Montgomery, J., Gear, J., Prinsloo, F. R., Kahn, M., Kirsh, Z. G. S. Afr. med. J. 1955, 29, 608. 6. Suckling, P. V., Vogelpoel, L. Med. Proc. 1958, 4, 372. 7. Simenhoff, M. L., Uys, C. J. ibid. p. 389. 8. Naudé, W. du T., Seltzer, G., Kipps, A. ibid. p. 397. 9. Kipps, A., Naudé, W. du T., Don, P., Cooper, E. D. ibid. p. 401.
virus infections were prevalent in the general community, and the probable source of infection was two pregnant women who were admitted with Bornholm disease in the incubation period. The idea that the very young infant is especially susceptible to Coxsackie-virus myocarditis is supported by the observation that only those infants born after the first case in each outbreak became ill or infected, whereas all those born before that date showed no disease and no virus was isolated from their fxces, although all were nursed under the same conditions in a common nursery. The possibility of intrauterine infection was excluded by the absence of virus excretion or of antibody production in relevant mothers. The vulnerability of the neonate, which is in keeping with that of newborn suckling mice and of monkeys, may be related to the high level of circulating corticosteroids in the newborn; it has been shown that Coxsackie B3 virus causes myocardial necrosis in adult mice only if they are treated with cortisone.1o The Cape Town report underlines the value of teamwork by clinicians, pathologists, virologists, and epidemiologists in tackling an epidemic of an ill-understood infection. Alertness at the onset and full use of modern techniques in identifying the causal agent converted another " idiopathic virus x mystery " into an identified infection from which valuable experience has been gleaned. The Cape Town workers stress that Coxsackievirus myocarditis may be overlooked in a case of sudden death or in the absence of specific investigations. Clearly it is important to study carefully all unexpected deaths in infancy.11 The frequency of sporadic Coxsackie-virus infection is unknown; but Hosier and Newton 12 draw attention to two fatal cases observed in Ohio in the absence of a community or hospital epidemic, and they suggest that Coxsackie myocarditis can occur in the older child and adult. RATE OF INFUSION
THERE is much variation in the rate of administration by intravenous infusion of solutions intended to maintain the body content of water and electrolytes. Neyzi et al.13 have investigated the effects of variation in the rate of administering a multiple-electrolyte solution containing sodium, potassium, chloride, phosphate, and lactate.14 In preliminary experiments they established that healthy persons responded similarly to intravenous and to oral administration of this solution. They employed three different rates of oral administration, and their volunteers starved for 12 hours before and throughout the 72-hour period of study. In one pair of subjects the 24 hours’ ration of solution was given in equal doses at hourly intervals; in another pair the whole 24-hour ration was spread evenly over the first 12 hours of the 24-hour period; and in the third pair the total ration was given during the first 6 hours, which was followed by 18 hours of thirst and starvation. There were few symptoms in the subjects who received fluid throughout the 24 hours, but in the other two groups thirst and hunger were appreciable during the fasting periods. The steady provision of fluid did not tax in any way the capacity of the body to excrete the added water and electrolyte, but when the fluid was administered during the shorter periods there was wider fluctuation in 10. Kilbourne, E. D., Wilson, C. B., Perrier, D. J. clin. Invest. 1956, 36, 363. 11. See Lancet, Sept. 6, 1958, p. 513. 12. Hosier, D. M., Newton, W. A., Jr. Amer. J. Dis. Child. 1958, 96, 251. 13. Neyzi, O., Bailey, M., Talbot, N. B. New Engl. J. Med. 1958, 258, 1239. 14. Talbot, N. B., Kerrigan, G. A., Crawford, J. D., Cochran, W., Terry, M. ibid. 1955, 252, 856, 898.
min simply reflects some underlying defect which also leads to accumulation of copper in the body tissues, it is difficult to see what might be gained by raising the level of cseruloplasmin artificially; but this certainly should be tried. NEONATAL MYOCARDITIS
WHILE investigating an outbreak of poliomyelitis in the village of Coxsackie, Dalldorf and Sickles1 isolated a hitherto unrecognised filterable agent from the fasces of two children with lower limb paralysis. Attempts to isolate the virus in rhesus monkeys were unsuccessful, but paralysis was induced in newborn suckling mice. This discovery heralded the advent of a new family of viruses, which are now recognised as responsible for such infections as Bornholm disease and herpangina, and also for some epidemics of aseptic meningitis and of neonatal myocarditis. During an epidemic of Summer-grippe in adults in Amsterdam in 1955 23 four fatal cases of myocarditis were observed in newborns. The diagnosis was suggested by a preceding febrile illness in three mothers, followed by the onset in their infants of dyspnoea, cyanosis, or pallor; in two instances there were electrocardiographic abnormalities. Necropsy revealed diffuse interstitial myocarditis, and in all instances Coxsackie virus group B, type 4, was isolated from the heart-muscle. The strain of virus involving the myocardium was similar to non-myocardial strains obtained at the same time from patients with pleurodynia and aseptic meningitis. Whereas the virus produced fever and transient virasmia in two six-month-old monkeys, it caused fatal myocarditis in a two-day-old monkey. Reports from other countries have also implicated the Coxsackie virus as the cause of neonatal myocarditisnone more convincingly than those from South Africa, which has had maternity-home epidemics in Johannesburg in 1952/ in nearby Southern Rhodesia in 1954,5 and in Cape Town in 1957.6-9 The onset of illness in the Cape Town maternityhome epidemic in April and June, 1957, was marked by fever, cyanosis, red throat, limpness, vomiting, and dyspnoea in European infants aged 5-8 days. Disproportionate tachycardia, triple rhythm, and a widespread precordial systolic murmur denoted severe infection, while hepatomegaly due to cardiac failure was of grave prognostic import. Changes consistent with seen in were myocarditis electrocardiographs of each of five infants in whom this examination was made; and the tracings subsequently returned to normal in the four survivors. A group-B, type-3 Coxsackie virus was isolated from the faeces of four who recovered and from the heart of four who died. There appeared to be a clear relation between the duration of illness, the acuteness of the myocardial lesion, and the concentration of virus in the heart-muscle. In an infant who died after 2 days’ illness there was acute myocarditis and the myocardial virus titre was very high. At the other extreme, the heart of an infant who died after 11 days’ illness showed evidence of tissue repair and the myocardial virus titre was low. This epidemic occurred at a time when Coxsackie1. Dalldorf, G., Sickles, G. M. Science, 1948, 108, 61. 2. Van Creveld, S., De Jager, H. Ann. pœdiat., Basle. 1956, 187, 100. 3. Verlinde, J. D., van Tongeren, H. A. E., Kret, A. ibid. p. 113. 4. Javett, S. N. Heymann, S., Mundel, B., Pepler, W. J., Lurie, H. I., Gear, J. H. S., Measroch, V., Kirsch, Z. J. Pediat. 1956, 48, 1. 5. Montgomery, J., Gear, J., Prinsloo, F. R., Kahn, M., Kirsh, Z. G. S. Afr. med. J. 1955, 29, 608. 6. Suckling, P. V., Vogelpoel, L. Med. Proc. 1958, 4, 372. 7. Simenhoff, M. L., Uys, C. J. ibid. p. 389. 8. Naudé, W. du T., Seltzer, G., Kipps, A. ibid. p. 397. 9. Kipps, A., Naudé, W. du T., Don, P., Cooper, E. D. ibid. p. 401.
virus infections were prevalent in the general community, and the probable source of infection was two pregnant women who were admitted with Bornholm disease in the incubation period. The idea that the very young infant is especially susceptible to Coxsackie-virus myocarditis is supported by the observation that only those infants born after the first case in each outbreak became ill or infected, whereas all those born before that date showed no disease and no virus was isolated from their fxces, although all were nursed under the same conditions in a common nursery. The possibility of intrauterine infection was excluded by the absence of virus excretion or of antibody production in relevant mothers. The vulnerability of the neonate, which is in keeping with that of newborn suckling mice and of monkeys, may be related to the high level of circulating corticosteroids in the newborn; it has been shown that Coxsackie B3 virus causes myocardial necrosis in adult mice only if they are treated with cortisone.1o The Cape Town report underlines the value of teamwork by clinicians, pathologists, virologists, and epidemiologists in tackling an epidemic of an ill-understood infection. Alertness at the onset and full use of modern techniques in identifying the causal agent converted another " idiopathic virus x mystery " into an identified infection from which valuable experience has been gleaned. The Cape Town workers stress that Coxsackievirus myocarditis may be overlooked in a case of sudden death or in the absence of specific investigations. Clearly it is important to study carefully all unexpected deaths in infancy.11 The frequency of sporadic Coxsackie-virus infection is unknown; but Hosier and Newton 12 draw attention to two fatal cases observed in Ohio in the absence of a community or hospital epidemic, and they suggest that Coxsackie myocarditis can occur in the older child and adult. RATE OF INFUSION
THERE is much variation in the rate of administration by intravenous infusion of solutions intended to maintain the body content of water and electrolytes. Neyzi et al.13 have investigated the effects of variation in the rate of administering a multiple-electrolyte solution containing sodium, potassium, chloride, phosphate, and lactate.14 In preliminary experiments they established that healthy persons responded similarly to intravenous and to oral administration of this solution. They employed three different rates of oral administration, and their volunteers starved for 12 hours before and throughout the 72-hour period of study. In one pair of subjects the 24 hours’ ration of solution was given in equal doses at hourly intervals; in another pair the whole 24-hour ration was spread evenly over the first 12 hours of the 24-hour period; and in the third pair the total ration was given during the first 6 hours, which was followed by 18 hours of thirst and starvation. There were few symptoms in the subjects who received fluid throughout the 24 hours, but in the other two groups thirst and hunger were appreciable during the fasting periods. The steady provision of fluid did not tax in any way the capacity of the body to excrete the added water and electrolyte, but when the fluid was administered during the shorter periods there was wider fluctuation in 10. Kilbourne, E. D., Wilson, C. B., Perrier, D. J. clin. Invest. 1956, 36, 363. 11. See Lancet, Sept. 6, 1958, p. 513. 12. Hosier, D. M., Newton, W. A., Jr. Amer. J. Dis. Child. 1958, 96, 251. 13. Neyzi, O., Bailey, M., Talbot, N. B. New Engl. J. Med. 1958, 258, 1239. 14. Talbot, N. B., Kerrigan, G. A., Crawford, J. D., Cochran, W., Terry, M. ibid. 1955, 252, 856, 898.