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manufacturer's literature no actual recommendation as to the concentration of the drug is stated. It has been our practice to administer 200 mg of Praxilene in 500 ml of dextrose saline or physiological saline, and with this thrombophlebitis is not a problem. As it would seem that any local reactions can be avoided by using larger amounts of diluting fluid it would seem advisable, in view of the above report, that this recommendation should be included in the prescribing information. J CHAMBERLAIN Newcastle General Hospital, Newcastle upon Tyne

SIR,-I was most interested in the communication from Mr C.A J Woodhouse and Mr 0 G A Eadie concerning the intravenous administration of naftidrofuryl oxalate (Praxilene). For the past three years we have used it intravenously, 200 mg in 500 ml of dextrose solution given over a two-hour period. Infusion is then interrupted and recommenced in 12 hours' time. Using this technique we have had no evidence of thrombophlebitis. W MORRIS-JONES Sheffield

Vitamin D "resistance" and the bioavailability of calciferol tablets SIR,-Dr A M Parfitt (4 June, p 1470) feels that poor quality of the vitamin D preparation might underly the apparent resistance to vitamin D in my case of hypoparathyroidism with medullary carcinoma of the thyroid. The patient was at first treated with calciferol BP and required 7-5 mg daily at a time when other patients on the same preparation were on the usual dose in the range 0 6-2 0 mg daily. We then treated him with the UCH/Wander preparation of vitamin D.2 in arachis oil recommended for its accuracy by Parfittl and the late Professor C E Dent; his requirement with this preparation was 6 mg daily. It seems clear that the quality of the vitamin D preparation was not a factor in my patient's exceptional vitamin D requirement. C R PATERSON Ninewells Hospital, Dundee

Parfitt, A M, Australasian Annals of Medicine, 1968, 17, 56.

Epilepsy and drowning in childhood SIR,-I fear the short report by Dr J H Pearn (11 June, p 1510) will be misunderstood and that the statements that 54 % of immersion accidents were due to epilepsy and that children with epilepsy are four times more likely to drown than normal children will be believed. Education authorities, and in particular their legal advisers, may take these figures as basis for action. Eight qlildren are described, if wh two died-that is, only two were really "drowned." The youngest two children, aged 11 months and 2 years 8 months respectively, were left unattended in the bath and the younger died. This is, I think, much more a problem of the ordinary supervision of babies and young children than of any specific danger of epilepsy.

Of the other six children, four were mentally retarded. This seems a high proportion of the total and one must note that all had poorly controlled epilepsy and three of the four were with their families, who were knowingly, therefore, taking the risk. Dr Pearn's curious comment about the lack of adequate blood levels of anticonvulsants in all these children makes one wonder about their general level of care. We are then left with two older children of normal intelligence with epilepsy. One was said to have poorly controlled epilepsy and, in Britain, would normally have been watched very carefully or not encouraged to swim. The other was a girl of 15 years who had had epilepsy when younger and was found drowned leaning over the side of a bath. She was, I think, only presumed to have had a fit. My conclusion from this analysis of the Brisbane Drowning Study would be that it shows no evidence of increased risk to the child with well-controlled epilepsy attending normal school who wishes to swim. However, one would need to know the educational practice with respect to children with epilepsy in that part of Australia to be sure of this. It may be that when originally offered the paper was longer and clearer, but I feel clarification is now required. Perhaps the references to all the quoted data could be given. The important question to my mind is, "Is there evidence of increased risk for children with well-controlled epilepsy who attend a normal school if they swim with supervision ?" If there is no such risk, then the discussion of the possible triggers to such events becomes unnecessary. B G R NEVILLE Newcomen Centre, Guy's Hospital, London SEI

9 JULY 1977

forward both in respect of efficacy and low toxicity. However, it will take a: long time before oestrogen receptor analyses are available to most patients with metastatic disease. Previously I was afraid that cytotoxic chemotherapy might vitiate the possibility of obtaining a remission by subsequent hormonal therapy. Of 10 patients relapsing after combination chemotherapy who were given tamoxifen, six achieved an objective response with a median duration of 10 -+ months. This has convinced me that combination chemotherapy does not interfere with subsequent hormonal treatment. Because of the increased response rate with cytotoxic therapy this should be the first choice for metastatic disease in patients over 70 years of age, especially with visceral involvement, if receptor analyses are not available. WILLY MATTSON Department of Radiotherapy, General Hospital, Malm6, Sweden Brown, I, and Ward, H W C, C,linical Oncology, 1976, 2, 105. 2 Jones, S E, et al, Cancer, 1975, 36, 90. 3 Mattsson, W, et al, Acta Radiologica, 1977, 16, 97. l Segaloff, A, Cancer Treatment Reviews, 1975, 2, 129.

SIR,-There have been a number of recent reports advocating the use of adjuvant chemotherapy in the treatment of primary operable breast cancer.' 3 In a recent review undertaken at this hospital 28022 (9,32) of women who survived 20 years or more after surgery (mean 25 6 years) had nodal metastases (range 1-8 nodes). Prolonged survival of women with breast cancer and involved axillary lymph nodes is therefore possible following radical surgery and this would seem to indicate that randomisation on the basis of nodal status alone may well give erroneous results from trials of adjuvant

chemotherapy.4 Combination chemotherapy in metastatic breast cancer SIR,-The exciting study on metastatic breast cancer recently reported by Dr T Priestman and others (14 May, p 1248) is, so far as I know, the first paper describing a randomised study of combined cytotoxic chemotherapy compared with hormonal therapy. On the basis of our own encouraging results with combination chemotherapy and those of others, resulting in an overall response rate of about 50-80 0O"I --I and the rather low effectiveness of hormonal therapy, especially in patients with visceral metastatic lesions,4 our breast cancer group has, since late 1976, been carrying out a similar randomised study in metastatic premenopausal breast cancer. We compare combination chemotherapy (vincristine, adriamycin, cyclophosphamide, and methotrexate) with oophorectomy. The role of the last as the established primary method for the treatment of metastases in premenopausal women, with an overall response rate of about 25 %, must be questioned when analyses of oestrogen receptors cannot be performed. It is too early to draw any definite conclusions from our trial but so far it is clear that the increased response rate with cytotoxic chemotherapy compared with hormonal treatment may very well justify the transient side effects of the cytostatic drugs. I agree with Dr Priestman and his colleagues that the patients tolerate combination chemotherapy very well. Tamoxifen treatment of oestrogenreceptor-positive metastases represents a step

IAN MCINTOSH J C M P MONTEIRO

G A WALSH W P GREENING Breast Unit, Royal Marsden Hospital, London SW3

Holland, J F, New England J7ournal of Medicine, 1976, 294, 440. British Medicaljournal, 1976, 2, 263. 3 British Medical Journal, 1976, 2, 832. 4 British MedicalJournal, 1977, 1, 336. Forrest, A P M, et al, British Medical Journal, 1977, 1, 361. 6 Bonnadonna, G, et a!, New England Journal of Medicine, 1976, 294, 405.

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Cervical smears SIR,-It is a great relief to see the paper by Drs A I Spriggs and 0 A N Husain (11 June, p 1516). At last the clinical cytologists have produced an authoritative statement on the need for and timing of cervical smears. It has been our experience in university health services that the routine cervical smear in the under-25 age group does not survive cost-benefit scrutiny. A survey in 10 university centres during 1976 covering over 3000 smears produced no cases of pre-cancer and we have been resisting demands from our patients for routine smears. In August 1968 Dr Husain, for the Office of Health Economics, produced a figure of approximately £1-75 for the cost of taking, processing, and examining a smear. Allowing for inflation and balancing against this increased efficiency and mechanisation, a

Epilepsy and drowning in childhood.

BRITISH MEDICAL JOURNAL 122 manufacturer's literature no actual recommendation as to the concentration of the drug is stated. It has been our practi...
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