He says that there is no physiological explanation of how the effect would occur. This makes the assumption that the recommended dietary allowances of the nutrients, which probably were attained by the children in our study, are sufficient to ensure optimal mental health as well as physical health. However, recommended dietary allowances have been determined on the basis of physical criteria: amounts of the nutrients that would prevent any clinical signs of dietary deficiency. There is no reason to assume that these amounts are adequate for optimal resistance to infection or improving lifespan,3 nor that they are adequate for optimal mental performance. Resistance to respiratory infection in apparently well fed children was increased with a supplement containing only vitamins A, C, D and thiamine,4 and also in factory workers receiving only vitamin C, 40 mg daily.' That we have no "physiological explanation" for these observations does not negate their validity. We also made clear that our message is to improve the diets of the children rather than depend on micronutrient supplementation. JOHN YUDKIN London NW8 9TA 1 Whitehead RG. Vitamins, minerals, schoolchildren, and IQ.
BMJ 1991;302:548. (9 March.) 2 Schoenthaler SJ, Amos SP, Eysenck HJ, Peritz E, Yudkin J. Controlled trial of vitamin-mineral supplementation: effects on intelligence and performance. Personality and Individual Differences 1991;12:351-62. 3 Yudkin J. Nutritional requirements. Update 1970;Dec: 1539-46. 4 Yudkin J. The nutritional requirements of Cambridge schoolchildren. BMJ 1944;57:201-5. 5 Charley VLS, Mumford P, Yudkin J. Nutritional status in the Forest of Dean. Medical Officer 1952;88:83-5.
Chest pain in the accident and emergency department SIR,-Mr S S Tachakra and colleagues have an encouragingly low diagnostic error rate for patients with chest pain discharged from the accident and emergency department.' They did not, however, comment on errors made in interpretation of electrocardiographs and their effect on patient management. In a recent study performed in the accident and emergency department of the Ulster Hospital 43% of abnormal and 10% of normal electrocardiograhs were misinterpreted by casualty officers but resulted in the mismanagement of only 7 of 279 (2 5%) patients. To minimise inappropriate discharge of patients with chest pain from the accident and emergency department we recommend regular audit of electrocardiographs within 12 hours of the patient's attendance by the cardiologist on call. This will not overburden the cardiologist (there was an average of three electrocardiographs a day in Mr Tachakra's department) and may improve the error rate. W A McCALLION
Ulster Hospital, Belfast BT16 ORH 1 Tachakra SS, Pawsey S, Beckett M, Potts D, Idowu A. Outcome of patients with chest pain discharged from an accident and emergency department. BAM7 1991;302:450-5. (2 Miarch.) 2 McCallion WA, Templeton PA, McKinney LA, Higginson JDS. Interpretation of electrocardiographs in the accident and emergency department. Br Heart]7 1990;64:65. 3 McCallion WA, Templeton PA, McKinney LA, Higginson JDS. Missed m ocardial ischaemia in the accident and emergency department: a need for ECG audit? Arch Emerg Med (in press.,)
SIR,-We believe that Mr S S Tachakra and colleagues run the risk of increasing their workload and undermining their general practitioner colleagues by drawing inappropriate conclusions from their study.' There is little evidence in this study to support the statements that "All patients over 50 with chest pain should have electrocardio-
BMJ
VOLUME
302
23
MARCH
1991
graphy" and that "accident and emergency departments would be the most appropriate place to assess patients with chest pain." The value of a clinical test depends on the pretest probability that the patient has the condition under consideration and the change in this probability that a positive or negative test result will produce.2 A man over 50 years old who smokes and has a history of raised blood pressure and who then presents with a history of "heavy" chest pain with radiation down his left arm has a very high probability of a diagnosis of myocardial infarction. An electrocardiogram is not needed for the diagnosis and will not influence the management. Compare such a man with a woman who does not smoke and has normal blood pressure and who then presents with a "stabbing" pain which has no association with exercise. She has a very low probability of a diagnosis of myocardial infarction. Any abnormal electrocardiographic findings are likely to be false positives and might result in inappropriate management. In both cases the electrocardiogram is not helpful. Because the predictive value of any symptom, sign, or diagnostic test is affected by the prevalence of the disease, hospital based studies are generally unhelpful to general practitioners, who deal with a different population of patients. Among their many functions general practitioners operate as a "sieve" to assess whether a patient needs to be referred to hospital or not. They also play a part in modifying people's use of health care.3 By stating that "accident and emergency departments would be the most appropriate place to assess patients with chest pain" Mr Tachakra and colleagues seek to remove this sieve and change people's behaviour. In our practice in Cardiff (serving 7000 patients) we saw 194 patients with chest pain in 1988. If these data are extrapolated to the catchment area served by our accident and emergency department and this policy was introduced we would expect 11 500 patients each year to attend with chest pain. Sending all of these patients to the local accident and emergency department would cause great inconvenience to the patients and be a very inappropriate use of resouttes. We note from the data of Mr Tachakra and colleagues that 46% of a self referred group of patients required admission. This appropriate use of emergency resources would also be undermined by their suggested policy. PAUL KINNERSLEY PENNY OWEN CLARE WILKINSON
Department of General Practice, University of Wales College of Medicine, Cardiff CFH 7PN 1 Tachakra SS, Pawsey S. Beckett M, Potts D, Idowu A. Outcomes of patients with chest pain discharged from an accident and emergency department. BMJ 1991;302:504-5. (2 March.) 2 Sackett DL, Haynes RB, Tugwell P. The interpretation of diagnostic data. In: Sackett DL, Haynes RB, Tugwell P, eds. Clinical epidemiology. Boston: Little, Brown, 1985:59-138. 3 Stott NCH, Davis RH. The exceptional potential in each primary care consultation. J R Coll Gen Pract 1979;29:201-5.
Cardiac cachexia SIR,-The editorial by Dr W L Morrison and Professor R H T Edwards was most informative about the mechanisms underlying this unusual condition and emphasised the major catabolic defect identified as reduced protein synthesis,' but it failed to mention one potential line of therapy needing further attention-namely, treatment with human growth hormone. We were able to study in some detail one patient with severe cardiac cachexia in whom treatment with growth hormone was tried as a last resort (the patient had been deemed unsuitable for cardiac transplantation), with a remarkable beneficial effect. The patient before treatment was confined to bed, unable to feed or dress himself, and had a
cardiac output of 2 I/min, but subsequently he was discharged from hospital and now lives on his own.2 In this case the aetiology of the cardiac cachexia was most probably infective postoperative complications in a patient who had suffered from many years with severe Cushing's disease, complicated by hypertension and insulin dependent diabetes mellitus. The patient had been cured but at the same time rendered panhypopituitary by transphenoidal hypophysectomy in November 1986. By the time he presented with heart failure in August 1987 he had lost considerable weight (about 16 kg). Despite all conventional treatments his heart failure got worse and he was eventually confined to bed, unable even to feed himself without help. Within a few days of starting treatment with human growth hormone (Genotropin (Kabi), 12 units daily at 2200) there was obvious improvement in wellbeing as well as cardiac state, in keeping with the then unrecognised but now documented central effects of growth hormone treatment.3 Mobility improved over the next few months until he could walk indefinitely on the flat and climb two flights of stairs with only mild dyspnoea. Protein anabolism in vivo in humans seems to be regulated primarily by substrate availability,4 while growth hormone stimulates synthesis' and insulin inhibits protein breakdown.6 Cortisol inhibits
protein synthesis, accounting for the reduced muscle mass in patients with Cushing's syndrome.7 Because of increased availability growth hormone is now a potentially important new therapeutic agent in states associated with increased protein catabolism and reduced protein synthesis. It has been shown to reduce or eliminate the catabolic response to surgery, burns, and prednisolone treatment8 as well as to have profound effects on body composition in patients with growth hormone deficiency,9 favouring lean body mass and reducing body fat. In these patients it also improved muscle performance.'" Taken in conjunction with the recent work showing a beneficial effect in elderly normal men" these results indicate a potentially powerful and new therapeutic role for growth hormone in humans. Growth hormone might benefit patients with cardiac cachexia by promoting both cardiac and skeletal muscle anabolism and by a direct inotropic action. 12 A trial in such patients seems worth while, and we would be interested in hearing from anyone interested in pursuing this further. P H SONKSEN F SALOMON R CUNEO M UMPLEBY S BOWES
Department of Endocrinology and Chemical Pathology, St Thomas's Hospital, London SE 1 7EH 1 Morrison WL, Edwards RHT. Cardiac cachexia. BMJ 1991; 302:301-2. (9 February.) 2 Cuneo RC, Wilmshurst P, Lowy C, McGauley G, Sonksen PH. Cardiac failure responding to growth hormone. Lancet 1989;i: 838-9. 3 McGauley GA. Quality of life assessment before and after growth hormone treatment in adults with growth hormone deficiency. Acta Paediatr Scand 1989;356:70-2 4 Tessari P, Inchiostro S, Biolo G, et al. Differential effects of hyperinsulinaemia and hyperaminoacidaemia on leucinecarbon metabolism in vivo. J Clin Invest 1987;79:1062-9. 5 Horber FF, Haymond MW. Human growth hormone prevents the protein catabolic side effect of prednisolone in humans. J Clin Invest 1990;86:265-72. 6 Fukagawa NK, Minaker KL, Rowe JW, et al. Insulin mediated reduction of whole body protein breakdown: dose response effects on leucine metabolism in post absorptive men. J Clin Invest 1985;76:2306-1 1. 7 Bowes SB, Scobie IN, Benn JJ, Umpleby AM, Sonksen PH. Glucose and leucine tumover are reduced in Cushing's syndrome. Diabetologia 1987;30:503A. 8 Ziegler TR, Young LS, Ferrari-Baliviera P, Demling RH, Wumore DW. Use of human growth hormone combined with nutritional support in a critical care unit. J Parenter Enteral Nutr 1990;14:574-81. 9 Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl3rMed 1989;321:1797-1803.
725
BMJ 1991;302:548. (9 March.) 2 Schoenthaler SJ, Amos SP, Eysenck HJ, Peritz E, Yudkin J. Controlled trial of vitamin-mineral supplementation: effects on intelligence and performance. Personality and Individual Differences 1991;12:351-62. 3 Yudkin J. Nutritional requirements. Update 1970;Dec: 1539-46. 4 Yudkin J. The nutritional requirements of Cambridge schoolchildren. BMJ 1944;57:201-5. 5 Charley VLS, Mumford P, Yudkin J. Nutritional status in the Forest of Dean. Medical Officer 1952;88:83-5.
Chest pain in the accident and emergency department SIR,-Mr S S Tachakra and colleagues have an encouragingly low diagnostic error rate for patients with chest pain discharged from the accident and emergency department.' They did not, however, comment on errors made in interpretation of electrocardiographs and their effect on patient management. In a recent study performed in the accident and emergency department of the Ulster Hospital 43% of abnormal and 10% of normal electrocardiograhs were misinterpreted by casualty officers but resulted in the mismanagement of only 7 of 279 (2 5%) patients. To minimise inappropriate discharge of patients with chest pain from the accident and emergency department we recommend regular audit of electrocardiographs within 12 hours of the patient's attendance by the cardiologist on call. This will not overburden the cardiologist (there was an average of three electrocardiographs a day in Mr Tachakra's department) and may improve the error rate. W A McCALLION
Ulster Hospital, Belfast BT16 ORH 1 Tachakra SS, Pawsey S, Beckett M, Potts D, Idowu A. Outcome of patients with chest pain discharged from an accident and emergency department. BAM7 1991;302:450-5. (2 Miarch.) 2 McCallion WA, Templeton PA, McKinney LA, Higginson JDS. Interpretation of electrocardiographs in the accident and emergency department. Br Heart]7 1990;64:65. 3 McCallion WA, Templeton PA, McKinney LA, Higginson JDS. Missed m ocardial ischaemia in the accident and emergency department: a need for ECG audit? Arch Emerg Med (in press.,)
SIR,-We believe that Mr S S Tachakra and colleagues run the risk of increasing their workload and undermining their general practitioner colleagues by drawing inappropriate conclusions from their study.' There is little evidence in this study to support the statements that "All patients over 50 with chest pain should have electrocardio-
BMJ
VOLUME
302
23
MARCH
1991
graphy" and that "accident and emergency departments would be the most appropriate place to assess patients with chest pain." The value of a clinical test depends on the pretest probability that the patient has the condition under consideration and the change in this probability that a positive or negative test result will produce.2 A man over 50 years old who smokes and has a history of raised blood pressure and who then presents with a history of "heavy" chest pain with radiation down his left arm has a very high probability of a diagnosis of myocardial infarction. An electrocardiogram is not needed for the diagnosis and will not influence the management. Compare such a man with a woman who does not smoke and has normal blood pressure and who then presents with a "stabbing" pain which has no association with exercise. She has a very low probability of a diagnosis of myocardial infarction. Any abnormal electrocardiographic findings are likely to be false positives and might result in inappropriate management. In both cases the electrocardiogram is not helpful. Because the predictive value of any symptom, sign, or diagnostic test is affected by the prevalence of the disease, hospital based studies are generally unhelpful to general practitioners, who deal with a different population of patients. Among their many functions general practitioners operate as a "sieve" to assess whether a patient needs to be referred to hospital or not. They also play a part in modifying people's use of health care.3 By stating that "accident and emergency departments would be the most appropriate place to assess patients with chest pain" Mr Tachakra and colleagues seek to remove this sieve and change people's behaviour. In our practice in Cardiff (serving 7000 patients) we saw 194 patients with chest pain in 1988. If these data are extrapolated to the catchment area served by our accident and emergency department and this policy was introduced we would expect 11 500 patients each year to attend with chest pain. Sending all of these patients to the local accident and emergency department would cause great inconvenience to the patients and be a very inappropriate use of resouttes. We note from the data of Mr Tachakra and colleagues that 46% of a self referred group of patients required admission. This appropriate use of emergency resources would also be undermined by their suggested policy. PAUL KINNERSLEY PENNY OWEN CLARE WILKINSON
Department of General Practice, University of Wales College of Medicine, Cardiff CFH 7PN 1 Tachakra SS, Pawsey S. Beckett M, Potts D, Idowu A. Outcomes of patients with chest pain discharged from an accident and emergency department. BMJ 1991;302:504-5. (2 March.) 2 Sackett DL, Haynes RB, Tugwell P. The interpretation of diagnostic data. In: Sackett DL, Haynes RB, Tugwell P, eds. Clinical epidemiology. Boston: Little, Brown, 1985:59-138. 3 Stott NCH, Davis RH. The exceptional potential in each primary care consultation. J R Coll Gen Pract 1979;29:201-5.
Cardiac cachexia SIR,-The editorial by Dr W L Morrison and Professor R H T Edwards was most informative about the mechanisms underlying this unusual condition and emphasised the major catabolic defect identified as reduced protein synthesis,' but it failed to mention one potential line of therapy needing further attention-namely, treatment with human growth hormone. We were able to study in some detail one patient with severe cardiac cachexia in whom treatment with growth hormone was tried as a last resort (the patient had been deemed unsuitable for cardiac transplantation), with a remarkable beneficial effect. The patient before treatment was confined to bed, unable to feed or dress himself, and had a
cardiac output of 2 I/min, but subsequently he was discharged from hospital and now lives on his own.2 In this case the aetiology of the cardiac cachexia was most probably infective postoperative complications in a patient who had suffered from many years with severe Cushing's disease, complicated by hypertension and insulin dependent diabetes mellitus. The patient had been cured but at the same time rendered panhypopituitary by transphenoidal hypophysectomy in November 1986. By the time he presented with heart failure in August 1987 he had lost considerable weight (about 16 kg). Despite all conventional treatments his heart failure got worse and he was eventually confined to bed, unable even to feed himself without help. Within a few days of starting treatment with human growth hormone (Genotropin (Kabi), 12 units daily at 2200) there was obvious improvement in wellbeing as well as cardiac state, in keeping with the then unrecognised but now documented central effects of growth hormone treatment.3 Mobility improved over the next few months until he could walk indefinitely on the flat and climb two flights of stairs with only mild dyspnoea. Protein anabolism in vivo in humans seems to be regulated primarily by substrate availability,4 while growth hormone stimulates synthesis' and insulin inhibits protein breakdown.6 Cortisol inhibits
protein synthesis, accounting for the reduced muscle mass in patients with Cushing's syndrome.7 Because of increased availability growth hormone is now a potentially important new therapeutic agent in states associated with increased protein catabolism and reduced protein synthesis. It has been shown to reduce or eliminate the catabolic response to surgery, burns, and prednisolone treatment8 as well as to have profound effects on body composition in patients with growth hormone deficiency,9 favouring lean body mass and reducing body fat. In these patients it also improved muscle performance.'" Taken in conjunction with the recent work showing a beneficial effect in elderly normal men" these results indicate a potentially powerful and new therapeutic role for growth hormone in humans. Growth hormone might benefit patients with cardiac cachexia by promoting both cardiac and skeletal muscle anabolism and by a direct inotropic action. 12 A trial in such patients seems worth while, and we would be interested in hearing from anyone interested in pursuing this further. P H SONKSEN F SALOMON R CUNEO M UMPLEBY S BOWES
Department of Endocrinology and Chemical Pathology, St Thomas's Hospital, London SE 1 7EH 1 Morrison WL, Edwards RHT. Cardiac cachexia. BMJ 1991; 302:301-2. (9 February.) 2 Cuneo RC, Wilmshurst P, Lowy C, McGauley G, Sonksen PH. Cardiac failure responding to growth hormone. Lancet 1989;i: 838-9. 3 McGauley GA. Quality of life assessment before and after growth hormone treatment in adults with growth hormone deficiency. Acta Paediatr Scand 1989;356:70-2 4 Tessari P, Inchiostro S, Biolo G, et al. Differential effects of hyperinsulinaemia and hyperaminoacidaemia on leucinecarbon metabolism in vivo. J Clin Invest 1987;79:1062-9. 5 Horber FF, Haymond MW. Human growth hormone prevents the protein catabolic side effect of prednisolone in humans. J Clin Invest 1990;86:265-72. 6 Fukagawa NK, Minaker KL, Rowe JW, et al. Insulin mediated reduction of whole body protein breakdown: dose response effects on leucine metabolism in post absorptive men. J Clin Invest 1985;76:2306-1 1. 7 Bowes SB, Scobie IN, Benn JJ, Umpleby AM, Sonksen PH. Glucose and leucine tumover are reduced in Cushing's syndrome. Diabetologia 1987;30:503A. 8 Ziegler TR, Young LS, Ferrari-Baliviera P, Demling RH, Wumore DW. Use of human growth hormone combined with nutritional support in a critical care unit. J Parenter Enteral Nutr 1990;14:574-81. 9 Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl3rMed 1989;321:1797-1803.
725
