so each can benefit from others' "hands on" experience. SABRI CHALLAH. NICHOLAS MAYS. Department of Community Medicine,. St Thomas's Hospital,.
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BRITISH MEDICAL JOURNAL
skeletal muscle, white blood cells, and brain in animal studies and children. He cites a recent study from California' in which iron deficiency was more common in infants with a history of recurrent infections and adds that it is uncertain whether the infections preceded or followed the iron deficiency. He fails to indicate, however, that a fall in plasma iron concentration is an integral part of the response to infection of any nature and persists during the septic period. This mechanism, leading to sequestration of iron in the liver and promoted by endogenous mediators of activated phagocytic cells, is important in host defence,2 probably by SIR,-We accept the points made by Mr J E A depriving micro-organisms- of a trace element Wickham in his letter of 26 April (p 1134) about essential for- growth, multiplication, and toxin the importance of clinical experience in the evalua- production.3 tion of new technology. However, clinical exThere is good evidence of adverse effects on perience is only one component of a rigorous clinical outcome of routine iron supplementation assessment; it is complementary to the special skill to iron deficient children with infection4 or malof evaluation. nutrition.5 A degree of caution should be exercised We are criticised for our lack of "hands on" before recommending "blind" provision or iron experience with lithotripsy. We were aware of this supplements to all children with iron deficiency. in designing the evaluation and therefore sought the advice of urologists in selecting outcome DAVID P TAGGART measures. Department of Peripheral Vascular Surgery, By contrast, we welcome the interest of Mr Royal Infirmary, Wickham in evaluation and the paper in which he Glasgow G31 2ER and his colleagues compare extracorporeal shock I Reeves JD, Yip R, Kiley VA, Dalhnan PR. Iron deficiency in wave lithotripsy with the alternatives (29 March, infants: the influence of mild antecedat infection. J Paediatr 1984;105:874-9. p 879). We would, however, like to point out a few 2 WR. Metabolic effects of infection. Progress in Food Bresel methodological weaknesses and errors in the NutrinoScience article. Over and above the inappropriate use of 3 Weinberg ED. Metal1984;8:43-75. starvation of pathogens by hosts. Bioscience historical controls the authors use different end1975;25:314-8. 4 Murray MJ, Murray AB, Murray MB, Murray CJ. l he adverse points to compare success of lithotripsy and the effect of iron repletion on the course of certain infections. Br alternative treatments. Simple statistical analysis MedJ 1978;ii: 113-5. of the results would have shown that the dif- 5 McFarlane H, Reddy S, Adcock KJ, Adeshina H, Cooke AR, Akene J. Immunity, transferrin and survival in kwashiorkor. ferences in the success rates -given could have BrMedJ 1970;iv:268-70. arisen purely by chance. In the costing there are a number of errors. Among the most important is the use of average inpatient cost in table IV as a measure of hotel AUTHOR'S REPLY,-I think it is difficult to draw expenses. In fact this figure includes both treat- conclusions about children, especially those in ment and hotel costs; treatment costs are therefore developed industrial societies, from a study of counted twice in the pricing of open and per- adult Somali nomads.' In Ibadan death was more cutaneous surgery. The use of average instead of common in children with kwashiorkor soon after marginal costs further exaggerates the bias in starting treatment if they had a low serum transfavour of lithotripsy, with its shorter length of stay ferrin value.' The causes of death in these children' were unknown and iron was only part of their compared with the alternatives. We hope that these points will demonstrate the treatment. It was assumed, without evidence, that' need for clinicians and those with skill in evalua- high'circulating concentrations of free iron had tion to collaborate in assessing new technology, contributed to the deaths. The evidence about iron and infection is equiso each can benefit from others' "hands on" vocal and many believe that iron deficiency may be experience. SABRI CHALLAH associated with increased susceptibility.3 Reeves NICHOLAS MAYS and Yip found that giving iron to 1 year old infants was not associated with- adverse effects.4 In my Department of Community Medicine, St Thomas's Hospital, opinion the weight of evidexice is greatly in favour London SEI 7EH of treating iron deficiency in'children in almost all circumstances. D P ADDY SIR,-Mr C R Charig (3-May, p 1199) misunder- Department of Paediatrics, stands my concern about "shillings and pence." I Dudley Road Hospital, entirely agree with him that the decision must be Birmingham B18 7QH taken on "benefits for the patient": in my opinion this requires a controlled trial. I regret that Mr 1 Murray MJ, Murray AB, Murray MB, Murray CJ. The adverse effects of iron repletion on the course of certain infections. Br Charig has been misinformed: Bloomsbury Health MedJ 1978;ii:1113-S. Authority assures me that the unit cost statistic for 2 McFarlane H, Reddy S, Adcock KJ, Adeshina H, Cooke AR, 1984-5 is £181-8 and that the statistic includes the Akene J. Immunity, transferrin and survival in kwashiorkor: BrMedJ 1970;iv:268-70. cost of surgical procedures. 2 Spodick DH. The randomized controlled clinical trial: Scientific and ethical bases. AmJMed 1982;73:420-5. 3 Spodick DH. Revascularization of the heart-numerators in search of denominators. Am HearzJ 1971;81:149-57. 4 DeWood MA, Spores J, Notske RN, et al. Medical and surgical management of myocardial infarction. Am3' Cardiol 1979;44: 1356-64. 5 DeWood MA, Heit J, Spores J, et al. Anterior transmural myocardial infarction: effects of surgical coronary reperfusion on global and regional left ventricular function. Journal of the American College ofCardiology. 1983;1: 1223-34. 6 DeWood MA. Reply to Spodick DH. Joumal of the American College of Cardiology. 1983;2:1240-1. 7 Spodick DH. Randomize the first patient: scientific, ethical and behavioral bases. AmJf Cardiol 1983;51:916-7.
JJJ JONES Department of Community Medicine, Leicester LEI 6TP
3 Oski FA. The non haematological effects ofiron deficiency. AmJ
Dis Child 1979;133:315-22. JD, Yip R. Lack of adverse side-effects of iron ferrous sulphate therapy in I year old infants. Pediatrics 1985;75: 352-5.
4 Reeves
Happiness is: iron
SIR,-The leading article by Dr A P Addy (12 April, p
%69) catalogues the non-haematological
Ghucocorticoid receptors in depressionSIR,-Dr L J Whalley anld colleagues are to be congratulatedl on their excellent article (2-9 March,
detrimental consequences of iron deficiency, with or without anaemia, on the metabolic function of p 859). Apart from the main finding of a reduced
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17 m,Ay 1986
number ofglucocorticoid receptors in the lymphocytes of patients with major depression (research diagnostic criteria "endogenous" and "psychotic" subgroups) in comparison with a group of chronic schizophrenics and normal controls, several points merit further discussion. Firstly, the methods describe blood as being taken between 1130 and 1230 (presumably the middle of the day) for assessment of cortisol values. There were no significant differences in cortisol values between the depressed group ofpatients and the other groups. It would have been informative to know whether or not the depressed patients actually had hypercortisolaemia. This would have been more likely to have been found in blood specimens taken later in the day, between 1300 and 1600. There is a high correlation between mean 24 hour plasma cortisol values and those in the early afternoon taken over this three hour subperiod. Shortening this subperiod to two hours causes a sharp decrease in the association. ' Secondly, the object of having a group of chronic schizophrenic patients for comparison was to deal with unknown variables related to hospital admission. This raises the question when admission occurred, and when the investigations occurred in relation to it. It is a new admission and its acute aspects (and presumably the anxiety produced) that produce changes in cortisol profiles.2 Thirdly, Dr Whalley and colleagues quite rightly point out in their discussion that the similar finding of reduced numbers of glucocorticoid receptors in the lymphocytes of patients with anorexia nervosa may be due to a common factor of reduced food intake and weight loss. However, the research diagnostic criteria, although stringent, do not require appetite and weight loss as essentials for diagnosing endogenous or psychotic depression. Some of the patients in the depressed group might therefore have had unchanged food intake and weight, or indeed increased food intake and weight (the authors do not say). If this were the case it would be of great interest to know whether there was a significant difference in glucocorticoid receptors between subgroups showing marked increases and marked decreases in food intake and weight. This difference might not be picked up on the ordinary correlation matrix which they have used.
BRIAN HARRIS Department of Psychological Medicine, University of Wales College of Medicine, Cardiff CF4 4XN
ROGER THOMAS Sully Hospital, South Glamorgan I Halbreich U, Asnis GM, Shindledecker MA, Zumoff B, Nathan
S. Cortisol secretion in endogenous depression. Arch Gen Psyckiaty 1985;42:904-8. 2 Berger M, Pirke KM, Doerr P, Krieg JC, Von Zerssen P. The
limnited utility of the dexamethasone suppression test for the diagnostic process in psychiatry. Br J Psychiatr 1984;145: 372-82.
AUTHoR's REPLY-Drs Harris and Thomas are correct to emphasise the importance ofserial blood sampling in the study of cortisol secretion. Previously we examined plasma cortisol concentrations over 17 hours in newly admitted psychiatric patients and, like many others, detected the greatest differences between patients and controls during the afternoon period.' The hypercortisolaemia of depressive illness was best distinguished, however, during the late evening (2300-2400). We related this to the hypothesis that the hypercortisolaemia of depression is linked to a phase advancement of the early morning increase in cortisol secretory activity. In our subsequent study of glucocorticoid receptor numbers in depressed patients we reasoned that the most informative time of sampling would be during the late evening.
