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though like the patients with other types of temporal-lobelesion they often had neurotic and psychopathic per-sonality disorders. Since this type of temporal-lobeepilepsy commonly starts in childhood, it is disappointinghow rarely the condition is judged suitable for operationbefore early adult life. One of the difficulties is that, asseveral workers have shown, the electroencephalograms(E.E.G.S) in such children often show generalised epilepticabnormalities, and even bilateral foci, which do not

crystallise into a clear cut unilateral temporal-lobe focusuntil adolescence. The Maudsley studies clearly show theimportance of an exhaustive preoperative work-up,including clinical history, psychological testing, E.E.G.

studies, and neuroradiology, if the best results are to beobtained from operation.

EXPERIMENTAL RUBELLA

UNTIL 1941 rubella was judged to be a trivial disease,but since then, when Gregg 1 recognised the virus to be ateratogen, it has presented a stream of awkward questionsto those who study it. Owing to the seeming incapacityof the virus to produce cytopathic effects in tissue-culture, twenty years were to elapse between Gregg’spaper and the isolation of the virus by Weller and Neva 2and by Parkman et awl. in 1962. The list of species oftissue-cultures in which the virus is now known to

replicate is becoming quite large 4 ; but in most of these(and surprisingly in most human tissue-cultures) virusgrowth does not produce visible cytopathic effects or celldeath, and chronic infection of cells is the common result.Unexpectedly, therefore, every test so far reported 5-12of the action of the virus on rabbit tissue-cultures hasdemonstrated cytopathic effects.The clear need is to study the mechanism of rubella

teratogenesis for the better understanding of the diseaseand how to prevent it. Although much has been learnedfrom the examination of human foetuses deliberatelyaborted because of maternal rubella, the natural occur-rence of rubella during pregnancy is too random and toorare for systematic detailed study of the mechanisms offoetal damage. A few attempts have been made to investi-gate the effect of attenuated rubella strains on the foetus

by injecting live vaccine into susceptible pregnant womenwho are due to be aborted for other compelling reasons,but the prospects of designing and carrying out usefulexperiments in these circumstances are limited-nor arethe ethics beyond question.A model system in a laboratory animal is certainly

needed, but the criteria for selecting a suitable system areprobably complex and certainly not fully known. Thebasic requirement is that the pregnant animal should becapable of being infected. Several animals have been

1. Gregg, N. M. Trans. Ophthal. Soc. Aust. 1941, 3, 35.2. Weller, T. H., Neva, F. A. Proc. exp. Biol. Med. 1962, 111, 215.3. Parkman, P. D., Buescher, E. L., Artenstein, M. S. ibid. p. 225.4. McCarthy, K., Taylor-Robinson, C. H. Br. med. Bull. 1967, 23, 185.5. McCarthy, K., Taylor-Robinson, C. H., Pillinger, S. E. Lancet, 1963, ii,

593.6. Beale, A. J., Christofines, G. Symposium International sur la Standardisa-

tion des Vaccins contre la Rougeole et la Sérologie de la Rubéole;p. 103. Lyons, 1964.

7. McCarthy, K., Taylor-Robinson, C. H. Arch. Virusforsch. 1965, 16, 415.8. Belcourt, R. J. P., Wong, F. C. ibid. p. 419.9. Reddick, A., Roesel, C. E. Science, N.Y. 1966, 151, 1405.

10. Leerhoy, J. ibid. 1965, 149, 633.11. O’Ryan, E. See McCarthy, K., Taylor-Robinson, C. H. Br. med. Bull.

1967, 23, 185.12. Hull, R. N., Butorac, G. Am. J. Epidemiol. 1966, 83, 509.

investigated: monkeys were an obvious choice,13 but costand space limit the numbers which can be used, and it ishard to achieve a pregnancy, let alone a timed pregnancy,in animals reluctant to mate in a laboratory cage. More-over, in laboratory monkeys gestation may last fivemonths, which would further restrict the scale of theexperiments. The human foetus is probably infectedthrough the placental circulation as the result of maternalviraemia, and therefore the method of placentation in alaboratory animal may be one of the features determiningthe usefulness of a species. Even though adults of aspecies are susceptible to generalised infection, they areof no use for this research if the placenta is of a typewhich prevents the virus from spreading to the foetus.Similarly the permeability of the placenta to antibodies ofvarious molecular sizes and types is likely to be importantin the evolution of the experimental infection and relevantto studies of the prevention of human infection by vac-cination. In addition to monkeys, rabbits,14 15 ferrets,16hamsters,l’ and rates 18 can be infected, but much morework is needed to assess the value of these and other

experimental systems.The article by Dr. Kono and his colleagues on p. 343 is

a step in this direction. They record a striking resem-blance between the pathological changes in baby rabbitsinfected in utero and in the human syndrome of congenitalrubella. The changes produced in the human foetus byrubella virus are thought to reflect a delicate balancebetween damage to and survival of cells-a balance notmatched in any other human infection. What is surprisingand exciting about the work of Dr. Kono and his asso-ciates is that this balance seems to have been struck atabout the same point in the rabbit embryo. If these

findings can be confirmed and extended, a useful modelsystem for the investigation of intrauterine infection willhave been achieved.

The Japanese work may also shed light on the reasonsfor the rarity of the congenital rubella syndrome in

J apan.19 Although the number of rabbits tested is as yetsmall, the incidence of abnormalities was significant onlyin those animals given the American strains of virus, andno abnormalities appeared in those given the Japanesestrains or in the controls (the size of the control group isvery small compared with the other two). Those whohave looked for abnormalities in foetal and newbornrabbits know that the random occurrence of spontaneousabnormalities can temporarily mislead and, in this sense,the findings of Dr. Kono and his colleagues must beregarded as preliminary. They are, however, supportedby confirmatory virological and immunological results insome of the does and their offspring. Why a virus whichachieves a unique host-parasite balance in man shouldreach a similar point of balance in the rabbit is unknown.The difference in rabbit virulence of American and

Japanese strains does not seem to be related to the lengthof history of tissue-culture passage, and our Japanese

13. Parkman, P. D., Phillips, P. E., Meyer, H. M. Am. J. Dis. Child. 1965,110, 390.

14. Selzer, G. S. Afr. med. J. 1965, 39, 1028.15. Belcourt, R. J. P., Wong, F. C., Walcroft, M. J. Can. J. publ. Hlth, 1965,

56, 253.16. Cusumano, C. L., Sever, J. L., Schiff, G. M., Huebner, R. J. Bact. Proc.

1965, p. 119 (abstract).17. Oxford, J. S., Schild, G. C. Virology, 1966, 28, 780.18. Cotlier, E., Fox, J., Bohigian, G., Blaty, C., Du Pree, A. Nature, Lond.,

1968, 217, 38.19. Kono, R. in Proceedings of 23rd Symposium on Microbiological

Standardisation, Rubella Vaccines. London, Nov. 18, 1968 (in thepress).

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contributors tentatively suggest that, although serologicaldifferences between the strains are not apparent, thedifference in their virulence for the rabbit embryo may bea reflection of their differing virulence for the humanfoetus.

Of course, since abortion is readily available in Japan,women who have had rubella in early pregnancy may seekand obtain an abortion so readily that the affected childrenare never born. In assessing this possibility, a review ofJapanese experience over the past twenty years would behelpful; and examination of aborted foetuses would revealwhether or not virus can be recovered from them. If, onthe other hand, Japanese women who contract rubellawhen pregnant do not in fact seek abortion on thataccount, and if there is no gross evidence of foetal damagewhen the children are born, it might be worth seeking anyserological evidence of subclinical intrauterine infection.

Satisfactory answers to the questions raised by thepaper of Dr. Kono and his colleagues could be directlyrelevant to the selection of strains of rubella virus forvaccines. All the prototype strains discussed at the inter-national rubella conference in London last November had

necessarily been derived from strains known to be terato-genic. New techniques were described at that meeting forthe detailed comparison of the antigenic similaritiesbetween rubella strains.2O 21 If the Japanese strains arefound to be immunologically identical with Western strainsand if they are significantly less teratogenic, they might bemore suitable stocks from which to derive strains for the

preparation of live vaccines.

SERUM-URIC-ACID AND CORONARY

HEART-DISEASE

EPIDEMIOLOGICAL study of coronary heart-disease hasidentified characteristics which, to varying extents, areassociated with an increased liability to cardiovasculardisease. Most investigations, including those of Morris etal .,22 demonstrate that levels of casual systolic blood-pressure and plasma-cholesterol are the predominantpredictive factors. Unfortunately, satisfactory means ofreducing blood-pressure and plasma-cholesterol are hardto find. Weight and cigarette-smoking are two influenceswhich can be modified, though only by changes in personalhabits. Two metabolic disorders, gout and diabetes, havebeen postulated as predisposing to coronary heart-disease.If raised serum-uric-acid levels are concerned in the

development of coronary heart-disease, that would beimportant, since effective treatment is available for gout.Gertler et aI. 23 noted an excess of hyperuricasmia in youngpatients with coronary heart-disease. Several other

reports have also observed the association of hyperuri-csemia with atherosclerosis.24-29 Others believe, however,20. Taylor-Robinson, C. H., Ratcliffe, H. ibid.21. Le Bouvier, G. L. ibid.22. Morris, J. N., Kagan, A., Pattison, D. C., Gardner, M. J., Raffle,

P. A. B. Lancet, 1966, ii, 553.23. Gertler, M. M., Garn, S. M., Levine, S. A. Ann. intern. Med. 1951,

34, 1421.24. Ask Upmark, E., Adner, M. L. Acta med. scand. 1950, 139, 1.25. Kramer, D. W., Perilstein, P. K., De Medeiros, A. Angiology, 1958,

9, 162.26. Dreyfus, F. Dis. Chest, 1960, 38, 332.27. Spring, M., Cavusoglu, M., Chu, Y. C., Artymowske, C. Circulation,

1960, 22, 817.28. Eidlitz, M. Lancet, 1961, ii, 1046.29. Hansen, O. E. Am. Heart J. 1966, 72, 570.

that gouty subjects are no more prone to coronary heart-disease than the non-gouty.30 A report from a largeepidemiological study 31 concluded that the higher inci-dence of coronary heart-disease in gouty subjects was realbut that the association between the risk of coronaryheart-disease and hyperuricaemia disappeared whenpeople with clinically overt gout were removed.

Analysis of uric-acid data from many investigations,including the Tecumseh Community Health Studies 32-31has shown that levels of uric acid are related to age, sex,and body-weight. In view of the interrelationship of otherfactors, including blood-pressure and serum-cholesterol,with age and weight, it is important to establish whetherthe level of uric acid is independent of the other findings,such as weight, blood-sugar, blood-cholesterol, and

blood-pressure.

Myers et aI.37 have now re-examined their own findingsfrom the initial examination cycle of the Tecumseh Com-munity Health Study. In the 1959-60 examination,serum-uric-acid levels in 6000 participants were measuredby the enzymatic spectrophotometric method of Liddle etal.38 Early work demonstrated the need to standardisethe individual serum-uric-acid levels to compensate for

systematic differences associated with the age and sexdistributions of the population studied. In succeedinganalyses still another variable emerged in association withserum-uric-acid-namely, relative weight. This measureis computed from a regression equation taking into accountactual weight, height, and biacromial and bicristaldiameters of the individual subject, and the relative

weight is stated as a ratio to the sex-specific value formen or women aged 20-29 years. This finding agreeswith the reports of an association between serum-uric-acid levels and body surface 39 or ponderal index .40

By means of this adjusted serum-uric-acid score, a pos-sible association was first examined with serum-choles-

terol, blood-sugar, and blood-pressure. No clear connec-tion could be demonstrated between levels of serum-uric-

acid, adjusted for age, sex, and relative weight, and levelsof blood-pressure, blood-sugar, or serum-cholesterol.Thus, if serum-uric-acid affects the incidence of coronaryheart-disease, the effect seems to be independent of itsinfluence on these other risk factors. When age, sex, andrelative weight are taken into account, the figures may beused to show that serum-uric-acid levels of persons with

coronary heart-disease are significantly different fromthe mean of the population studied, so that hyperuricaemiacan be taken to be an attribute associated with the disease.Of the other conditions studied, only gout and pregnancyalso differed significantly from the means of the entirepopulation with respect to serum-uric-acid scores. Thelevels of gouty subjects, as expected, were higher and ofpregnant women lower.

30. Talbott, J. H. Gout; p. 139. New York, 1964.31. Hall, A. P. Arthritis Rheum. 1965, 8, 846.32. Francis, T., Jr. Publ. Hlth Rep., Wash. 1961, 76, 863.33. Napier, J. A. Am. J. publ. Hlth. 1962, 52, 208.34. Epstein, F. H., Francis, T., Jr., Hayner, N. S., Johnson, B. C., Kjelsberg,

M. O., Napier, J. A., Ostrander, L. D. Jr., Payne, M. W., Dodge,H. J. Am. J. Epidemiol. 1965, 81, 307.

35. Johnson, B. C., Epstein, F. H., Kjelsberg, M. O. J. chron. Dis. 1965,18, 147.

36. Hayner, N. S., Kjelsberg, M. O., Epstein, F. H., Francis, T. Jr.Diabetes, 1965, 14, 413.

37. Myers, A. R., Epstein, F. H., Dodge, H. J., Mikkelsen, W. M. Am. J.Med. 1968, 45, 520.

38. Liddle, L., Seegmiller, J. E., Laster, J. J. Lab. clin. Med. 1959, 54, 903.39. O’Brien, W. M., Burch, T., Bunim, J. Ann. rheum. Dis. 1966, 25, 117.40. Acheson, R. M., O’Brien, W. M. Lancet, 1966, ii, 777.