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passing effect on cell turnover unrelated to chronic renaldamage ? The effect was not found with dummy tablets,but what about those containing drugs other than

analgesics ? The doses used were several times the

ordinary amount, save for addicts, and we need to knowmore about the cumulative effects of small doses.Prescott rightly suggests that attention should be paid toaspirin as well as to phenacetin as a potential cause ofrenal damage, though, on his results, caffeine should alsobe included, at least for those factory workers who drinkten cups of tea a day. These findings have less directbearing upon the basic problems cf analgesic nephropathy,though in time such studies may well contribute to theirsolution. If, as has been suggested, nephropathy isrelated to some contaminant, such as acetic 4-chloranilide,3 3or to the total cumulative dose consumed rather than tothe duration of exposure,4 there is a need for new methodsof investigation more powerful than the epidemiologicalor cell-excretion techniques available so far. There is,for example, no satisfactory experimental model of thehuman disease. The unpleasant possibility even existsthat one drug may be found to sensitise patients to theill-effects of another-a difficult proposition to test

experimentally. We still do not know how or whychronic nephropathy develops, or its exact relationshipto

" pyelonephritis ". The new findings help by showingthat acute nephrotoxic effects may arise with analgesics,and that their intensity can be measured. As Prescottshows by analogy with peptic ulcer, the acute and chroniceffects may be related. As with peptic ulcer, however,such analogies are fraught with logical pitfalls.

CAUSES OF CONGENITAL HEART-DISEASE

NEW information about the role of rubella in the xtio-

logy of congenital heart-disease was among the subjectsdiscussed by members from fifteen countries at the recentannual meeting of the Association of European Pxdia-tric Cardiologists in St. Andrews. Reporting the

experience of the Baltimore group after the great epidemicof this disease on the east coast of the United States last

year,5 Dr. Catherine Neill emphasised the great advancesin knowledge that have been made since it became

possible nor only to culture the virus but also to make anexact diagnosis in babies and very small children bycardiac catheterisation combined with selective cine-

angiocardiography. This American epidemic confirmedwhat was first demonstrated twenty years ago-thatrubella is a source, and indeed may be a terrible source, of

congenital wastage. It is now known that a foetus may beaffected even when the infection begins before gestation,that the virus remains in the foetus throughout intra-uterine life, and that the virus may be excreted or culturedfor up to six months after birth. The extraordinaryaffinity of the rubella virus for the sixth aortic arch hasalso been confirmed, and the virus is a powerful arterialteratogen causing persistence of the ductus arteriosusand stenosis of the pulmonary arteries. Though it hasoften been grown from the hearts of those who have

died, and there have been several fairly well-documentedcases of myocarditis, the virus seems to be rather a weakcardiac teratogen.

Prof. John Hay described how information about

3. Harvald, B., Valdorf-Hausen, F., Nielsen, A. ibid. 1960, i, 303.4. Moeschlin, S. Schweiz. med. Wschr. 1957, 87, 123.5. See Lancet, 1965, i, 1208.

possible aetiological factors in congenital malformationsis being obtained by the university department of childhealth in Liverpool, where a central registry has been setup with the cooperation of the Ministry of Health and thelocal authorities. An elaborate system has been devised torecord those malformations (up to 50%) that escapecompulsory notification to the central Government. Closeand willing cooperation from many hospitals and clinics,plus constant surveillance by social and public-healthworkers, has ensured that the great majority of congenitaldefects are available for statistical analysis. A simplemethod of wall-charting ensures that any increasedincidence soon becomes obvious and a search can be madefor possible setiological factors that began to operateduring the preceding nine months. The thalidomidetragedy was graphically recorded in this way; and tetra-cycline is at present under investigation, by reference tothe National Health Service prescription forms which arekept in a central office of the Ministry of Health. The

importance of this awesome administrative task is provedby prescriptions for thalidomide made out to the mothersof some babies without limbs, who said they had takenno tablets and whose doctors denied prescribing them.These carefully controlled investigations should shed

new light on infective and chemical factors in the aetiologyof congenital malformations, and at the same timedetermine the true incidence of the various anomalies atbirth. A long-term study of babies with congenital heart-disease is already under way and will help to define thesize of the diagnostic and therapeutic problem. It shouldbe useful, too, in highlighting, at any rate in this country,the extent to which pxdiatric cardiology has been

neglected; and the results will also be of value in planningfuture services, since the great majority of children whoare born with serious congenital heart-disease do notsurvive their first year of life, and many of those whosehearts fail early are the ones for whom most could bedone.

TREATMENT OF NEPHROBLASTOMA

ANY treatment of malignant tumours in childhood hasusually to be assessed from results in a small number ofpatients who have been treated by several methods. Aplan of treatment which simplifies the assessment of thevalue of a single agent is therefore welcome. Death fromnephroblastoma (Wilms’ tumour) is mainly due to blood-borne metastases, and it has been known for some yearsthat actinomycin D may inhibit the growth of pulmonarymetastases of nephroblastoma. Howard 1 has reviewedthe results of adding actinomycin D to the standardtreatment of nephroblastoma at the Royal Children’s

Hospital, Melbourne. A total dose of actinomycin of 120{jt.g. per kg. body-weight was given in 8 equal quantities.Nephrectomy was carried out after the third dose, andpostoperative irradiation was delayed until the 26th day.Of 18 consecutive patients treated in this way, 11 (62%)have survived without sign of recurrence for two to fiveyears-a great improvement on the previous survival-rate(11-5%) at the same hospital.2Howard reminds us of the toxic properties of this anti-

biotic : depression of bone-marrow, with a risk of aplasticansemia, macular rashes, epilation of the scalp, and anor-exia, vomiting, stomatitis, and bloody diarrhoea. Thesetoxic reactions vary from patient to patient and with

1. Howard, R. Archs Dis. Childh. 1965, 40, 200.2. Howard, R. Med. J. Aust. 1957, i, 200.