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We have not observed any remission in AML, but we didobtain (table) 2 complete and 2 partial (30%) remissions in16 patients with ALL and 2 complete and 1 partial (30%)remissions in leuksmic lymphosarcoma.2 The 37 patients hadbeen previously treated without success by other means.The most important characteristic of this anthracycline is

that, in contrary to doxorubicin or daunorubicin, it does notcause alopecia, and it induced only 3 cardiac manifestationsout of 35 patients evaluable for toxicity. This freedom fromalopecia induction and the low cardiac toxicity had been pre-dicted by our light-microscopy study of the skin and electron-microscopy of the myocardium on golden hamsters (to be pub-lished in Cancer Treatment Reports).

Institut de Cancérologieet d’Immunogénétique,

Hôpital Paul-Brousse,94800 Villejuif, France

G. MATHÉF. GESCHER M. A. GILM. BAYSSAS M. DELGADO

J. L. MISSET P. RIBAUDD. MACHOVER M. HAYAT

THE DIET/HEART CONTROVERSY

SIR,-The diet/heart controversy centres upon the lipidhypothesis which seeks to relate products of fat metabolismand injury to the arterial endothelium. In the absence of satis-factory direct experimental evidence, epidemiologists refer tonational statistics as a basis for identifying environmental riskfactors, among them the consumption of saturated fats. Aclassic example is the Seven Countries Study.

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Clearly, if intake of any item of diet increases the risk of dis-ease, populations with high intake should have a greater inci-dence than those with low intake. But if susceptibility is here-ditary (and survival characters are) different populations willhave a different incidence, whatever their diet. Any correlatedvariation in dietary habit may therefore be purely fortuitous,and certainly confounded with genetic variation. Therefore asecond condition is required-that within populations themean consumption of those with the disease is significantlygreater than those without. Denial of that is technically adeclaration of statistical independence. If a particular geno-type instinctively avoids an item of diet, as in hereditary fruc-tose intolerance, that will lead to a spurious negative correla-tion with the rejected item, and a spurious positive correlationwith its substitute. For present purposes, however, this compli-cation can be disregarded.

Seven countries were selected by Keys3 from twenty-threeO.E.C.D. member States. In 21 of those States national aver-

age consumption of animal fat and national mortality ratesfrom coronary heart-disease (CHD) were available. They fallnaturally into three genetic groupings: Japan, five Mediter-ranean countries, and fifteen Northern European (includingU.S.A.). The first two groups are characterised by a low con-sumption of animal fat (less than 6 g/day), and the third bya high consumption (more than 8 g/day).There are therefore two clusters (six and fifteen) defined by

fat consumption. Statistical analysis by covariance shows that,although the cluster mean CHD mortality-rates were signifi-cantly different, there was no evidence of any significant relá-tionship with fat consumption within them (+0-03±0-03 casesper 10 000 per g fat per day in the "six" and - 0.013±0.049in the "fifteen"). Hence, because the Seven Countries Studyincluded four from the six and three from the fifteen (out of116 280 possible sets of seven countries), a spurious positivecorrelation was unavoidable.

It is possible to obtain estimates of the quantity of saturatedfat eaten by CHD victims compared with others from internal

2. Mathé G, Bayssas M, Gouveia J, Dantchev D, Ribaud P, Machover D, Mis-set JL, Schwarzenberg L, Jasmin C, Hayat M. Preliminary results of aphase II trial of aclacinomycin in acute leukæmia and lymphosarcoma. Anoncostatic anthracyclin that is rarely cardiotoxic and induces no alopecia.Cancer Chemother Pharmacol 1978; 1: 259-62.

3. Keys A et al. Coronary heart disease in seven countries. Circulation 1970;41: suppl I.

evidence in Keys’ report, by a now well-known method.4 Thisrevealed highly significant differences between national meansaturated fat consumption, with Finland nearly 9% above andGreece 4-5% below average. It also showed a very highly sig-nificant difference between low and high fat villages. But therewas no evidence that, given the country and village of birthand domicile, those who died of CHD ate more saturated fatthan anyone else. In fact, though not significant, their meandaily intake was less. -

This is consistent with the suggestion that international vari-ation in CHD is genetic in origin, and that dietary fat is irrele-vant.

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Breeding Research Unit,Milk Marketing Board,Thames Ditton, Surrey KT7 0EL P. D. P. WOOD

ACTUAL OR STANDARD BICARBONATE

SIR,-Mr Lawrie and Mr Golda (July 28, p. 20) raise an in-teresting question. The standard bicarbonate replaced thealkali reserve some twenty years ago and was meant to indicatethe so-called "metabolic" element in acid-base changes in theblood. Now that PaC02 and pH are routine measurements inevery district hospital, perhaps it is time to abandon the stan-dard bicarbonate and report the actual bicarbonate concentra-tion. Along with this change we could with advantage discard"metabolic" in favour of "non-respiratory" and cease to askfor "base excess".

Calling all non-respiratory changes metabolic invites thededuction that they are deleterious and require correcting: theurge to inject hypertonic sodium bicarbonate when faced witha negative base excess is almost irresistible. One of the qualifi-cations for working in an intensive-care unit should, perhaps,be to exercise to the point of exhaustion and have one’s stan-dard bicarbonate and base excess measured and repeatedtwenty minutes later.

Clinicians the world over owe a great debt to Van Slyke andAstrup but they must be willing to discard some of their ter-minology in the light of subsequent developments.Shackleton Department of Anæsthetics,Southampton General Hospital,Southampton, SO9 4XY P. J. HORSEYFATAL LEISHMANIASIS IN RENAL-TRANSPLANT

PATIENT

SIR,-Infection is a well-recognised complication of im-munosuppressive therapy. The human kidney transplantregistry found that 45% of deaths were attributable to infec-tion and immunosuppression.! Various types of protozoal andparasitic infection have been reported in these patients.2 Wedescribe here a fatal case of leishmaniasis in an immunosup-pressed renal transplant patient.A 37-year-old gardener was admitted in 1977 for investiga-

tion of lethargy, fever, and pancytopenia. This patient hadmigrated to Australia from Malta 20 years previously. Therewas no history of leishmaniasis. In 1969, the patient had arenal transplant because of renal failure due to chronic pye-lonephritis in a multicystic horseshoe kidney. The .patient hadbeen haemodialysed for over a year before the transplant. Since1970, the patient had been treated with azathioprine and pred-nisone for chronic graft rejection. During his third post-trans-plant year, the patient visited Malta for about 2 months. Hewas symptom-free for 5 years thereafter until 1 month beforeadmission when Hb was noted to be 5.4 g/dl, white blood-cells1.3xlO9/1 (75% neutrophils), and platelets 120xl0"/l. Thiswas thought to be secondary to azathioprine which wasstopped. However, the patient’s condition did not improve andhe was admitted for further investigation. On physical examin-4. Yates F. The analysis of multiple classifications with unequal numbers in the

different classes. J Am Statist Assoc 1934; 29: 51-66.1. Advisory Committee to the Renal Transplant Registry. Thirtieth report of

the Human Renal Transplant Registry.2. Cameron TC. Problems with immunosuppressive agents in renal disease. J

Clin Path 1975; 28: suppl 9, p. 24.