1240
careful investigation of the differences between individuals with cerebral infarction and those with myocardial infarction. A major obstacle to an understanding of the similarities and differences between cerebral and myocardial infarction lies in the profusion of terms and diagnostic classifications used by researchworkers. The problem is especially serious for cerebral disease: "cerebral infarction", "cerebral thrombosis", "cerebral atherosclerosis", and "atherothrombotic brain infarction" are all used, with different shades of meaning. Moreover, diagnosis may be made clinically or at necropsy. Clinical diagnosis of cerebral infarction is not without error. HEASMAN and LIPWORTH12 found that a clinical diagnosis of "cerebral thrombosis" accorded with the post-mortem diagnosis in 45% of cases; in 11% cerebral or subarachnoid hxmor-
diagnosed at post-mortem, and in another 9% myocardial infarction was diagnosed. Before the xtiology of cerebral infarction can be properly investigated a uniform nomenclature and a common set of diagnostic criteria need to be rhage
was
defined. In the U.S.A. the National Institute of Neurological and Communicative Disorders and Stroke13 has attempted this, but its 52-page document seems too complex for widespread use. The classification system suggested by CAPILDEO and his colleaguesl4 seems more promising, but they have not specified the precise criteria by which cerebral infarction, cerebral hxmorrhage, and other forms of stroke should be diagnosed. Standard criteria, like those used to define myocardial infarction, would be useful. Emphasis should be given to the development of diagnostic criteria which balance the need to avoid misclassification errors with the need to maintain simplicity. The studies of HABERMAN et al. and their predecessors 1,3,5 are persuasive in challenging the widely held belief that cerebral infarction and myocardial infarction have a common cause. Because many of their arguments are based on mortality statistics, which are indirect and subject to diagnostic error, it is unwise to draw any firm conclusions from their work at this stage. However, these findings cannot be disregarded. It is clear that remarkably little is known about the factors which increase the risk of cerebral infarction or other forms of stroke, despite their being a very common cause of death. All too often stroke is investigated as a subsidiary analysis in a larger study of myocardial infarction. As the surveys were designed primarily to elucidate the risk factors associated with myocardial infarction and the analyses concentrated on the relationship of cerebral infarction with factors known to affect myocardial infarction risk, it is not surprising that they have been unrewarding with respect to Advisory Council for the National Institute of Neurological and Communicative Disorders and Stroke. Stroke, 1975, 6, 565. 14. Capildeo, R, Haberman, S., Rose, F. C. Br med. J. 1977, ii, 1578.
stroke.9 Surely it is time to look afresh at cerebral infarction-and to stop regarding it as a mere variant
of myocardial infarction. The Infant-food
Industry
IN those parts of the world which lack wealth and natural resources and where populations are often dense, breast-feeding of infants has become less common over the past thirty years. That is a striking misuse of one natural resource which many people could use to their benefit - namely, breast milk. The effect of this change in infant feeding has been keenly debated. The balance of judgment is that it has not been beneficial: as far as the evidence goes, diarrhoea and marasmus have not abated in artificially fed babies; biological child-spacing, as a consequence of lactation amenorrhoea, has come to have less influence on population control; and the cost to families and to nations who have bought the replacements for breast milk has been substantial. The causes of the decline in breast-feeding in Africa, Asia, and elsewhere include urbanisation and all that it entails (especially the desire of mothers to work and the aspiration towards Western styles); and the health services in many lands are ill designed to meet local needs when they offer maternity units which separate the mother from the newborn and when health professionals are inadequate in numbers and in education. Moreover, the industry which supplies artificial food for infants has long been active in encouraging the consumption of its products, often in circumstances where it is hard for a mother to prepare a bottle cleanly or for her family to afford the cost of filling it with nutritionally adequate contents.
From this story has sprung an argument which has concentrated largely on the promotional activities of the infant-food industry in the developing world. The Lancet has been among those who have criticised the industry,I which, after an initial response of shock and incredulity, formed the International Council of Infant Food Industries, a body which seeks to obtain recognition as a self-regulator of the industry. We invited the Council to set out its objectives in our columns; and its statement appears this week on p. 1250. With several large international companies not yet members, the Council has some way to go and its muscle as a deterrent to unacceptable promotional practices may prove feeble in the face of commercial pressures. But we believe that its offer of cooperation with scientists and academic institutes, with the international health agencies, and with governments should be given a hearing - as a welcome alternative to the wounding exchanges which have dominated this scene.
13.
15. Rose, G. A. Bull. Wld Hlth Org. 1962, 27, 645 1. See Lancet, 1976, ii, 503, ibid. 1977, i, 1067
1241
industry has reacted in other ways to the strictures heaped upon it. Less emphasis has certainly been put on "milk nurses", whose talks to mothers often seemed to discourage breast-feeding; and the aim is now said to be to "complete not compete" in infant feeding, though the assurance that the industry now works through the health profession (and with its express approval) carries small weight in countries where professionals are so few and poorly trained in nutrition. It remains to emerge how far these principles, which the industry is now more vigorously espousing, are convertible The
into actions which can surmount the dilemma of a conflict between profit making and public health. Meanwhile, the medical profession has its own path to tread. If programmes to support breastfeeding are to be convincingly encouraged and extended, more data must be gathered on the effects of different factors in different places, particularly the influences of education at all levels. For babies who must be bottle-fed, the need is for a non-advertised low-cost formula; and, for weaning, cheap multimix foods must be provided. Nutrition, of mothers as well as infants, is a deplorably neglected subject - in medical schools and in the councils of governments. It is clearly not a matter for further recrimination and litigation. If the infant-food industry is to find its proper role, it must stand up for I.C.I.F.I. and engage in a reasoned debate. If it fails to grasp this opportunity for reform, it will be subject to further criticism and calumny; and some governments may take action to exclude proprietary infant foods when they realise that they and their peoples could spend what money they have more wisely.
CARDIAC DEATH IN DIABETES ABOUT
50% of diabetic patients die from coronary
heart-disease,’ nearly double the rate in non-diabetics. This high mortality is accounted for not only by the frequency of coronary disease in diabetics but also by its severity. Acute myocardial infarction carries a poor early prognosis,2,3 and only half the patients admitted to hospital are alive after 12 months.4 The aetiology of heart-disease in diabetics is complex5-7-with probable contributions from hypertension, hyperlipidasmia, obesity, coagulation disorders, and microangiopathy. Myocardial infarction tends to present atypically in diabetics. About a third of patients have little or no pain,4,8 but rather slip insidiously into cardiac failure, shock, ketoacidosis, or even lactic acidosis. This painlessness has been attributed to autonomic neuropathy, but until 1. 2
Bradley, R. F. in Joslin’s Diabetes Mellitus (edited by A. Marble, P. White, R. F. Bradley, L. P. Krall), p. 417. Philadelphia, 1971. Soler, N. G., Pentecost, B. L., Bennett, M. A., Fitzgerald, M. G., Lamb, P., Malins, J. M. Lancet, 1974, i, 475.
3. 4.
Harrower, A. D. B., Clarke, B. F. Br med. J. 1976, i, 126. Soler, N. G., Bennett, M. A., Pentocost, B. L., Fitzgerald, M. G., Malins, J M. Q. Jl Med. 1975, 44, 125. 5. Harrower, A. D. B. Br. J. clin. Pract. 1977, 31, 47. 6. Page, M. M., Watkins, P. J. Clins Endocr. Metab. 1977, 6, 377. 7. Jarrett, J. ibid. p. 389. 8. Bradley, R. F., Schonfield, A. Geriatrics, 1962,17, 322.
there has been no evidence for this theory. Faeral. have now provided some such evidence. They did detailed histological work on the hearts of five diabetics who had just died with painless infarction, and on the hearts of similar-sized groups of diabetics and nondiabetics both with painful infarction and without infarction. They found degeneration and loss of sympathetic and parasympathetic fibres in all the cases of painless infarction but in none of the control groups. Three patients in the study group had other evidence of neuropathy and three had retinopathy (information was not available in one patient), but these complications were also common in the control diabetics. Several questions arise. Why was there no histological evidence of neuropathy in the hearts of the five diabetics who had no myocardial infarction, despite clinical evidence of neuropathy in four of them? It is surprising too that neuronal degeneration, often severe, was found in the study group, yet not even minor abnormalities were seen in the control groups. If neuropathy is the cause of painless myocardial infarction in diabetics, isolated degeneration of afferent cardiac nerves must be common, although other evidence of autonomic neuropathy affecting the cardiovascular system is uncommon. (Impotence may be a similar isolated manifestation of autonomic neuropathy in many male diabetics, and it is interesting that Faerman et al. found morphological similarities between the nerve lesions in the heart and abnormalities which they had previously found in the urinary bladder and corpora cavernosa of impotent diabetics.) The occurrence of painless infarction in non-diabetics also needs explanation and further histological studies of cardiac nerves are needed in both diabetics and non-diabetics. Cardiac enlargement and failure may arise in diabetics in the absence of overt myocardial infarction or other evidence of coronary heart-disease. This cardiomyopathic picture is often due to multiple infarcts caused by extensive occlusion of major coronary arteries, IO but there is increasing evidence that microangiopathy may also be responsible. Measurement of systolic time-intervals" and echocardiographyl2 suggests that subclinical myocardial dysfunction is very common in diabetics with other evidence of small-vessel disease. A histological investigation of cardiac microvascular disease was recently presented to the American Heart Association by S. Zoneralch. 13 Abnormalities of small intramural arteries were found in 36 out of 50 diabetics as against 9 of 32 controls. Half of the diabetics with small-vessel disease also showed disease of the larger coronary arteries, and nearly two-thirds of the diabetics had enlarged hearts and extensive myocardial fibrosis. Small vessels close to the sinus and atrioventricular nodes were often involved, and this may explain the low heart-rates which have been found after autonomic blockade in diabetics with autonomic neuropathy.14 Extensive vascular occlusion may well have an important role in myocardial infarction without pain, both in diabetics and in non-diabetics, and perhaps degeneration of
lately
man et
9.
Faerman, I., Faccio, E., Milei, J., Nunez, R., Jadinsky, M., Fox, D., Rapaport, M. Diabetes, 1977, 26, 1147. 10. Dash, H., Johnson, R. A., Dinsmore, R. E., Francis, C. K. Harthorne, J. W. Br. Heart J. 1977, 39, 740. 11. Seneviratne, B. I. B. Br. med. J. 1977, i, 1444. 12. Sanderson, J. E., Brown, D. J., Rivellese, A., Kohner, E. ibid. 1978, i, 404. 13. Cited in Diabetes Outlook, March, 1978. 14. Lloyd-Mostyn, R. H., Watkins, P. J. Br. med. J. 1975, iii, 15.
careful investigation of the differences between individuals with cerebral infarction and those with myocardial infarction. A major obstacle to an understanding of the similarities and differences between cerebral and myocardial infarction lies in the profusion of terms and diagnostic classifications used by researchworkers. The problem is especially serious for cerebral disease: "cerebral infarction", "cerebral thrombosis", "cerebral atherosclerosis", and "atherothrombotic brain infarction" are all used, with different shades of meaning. Moreover, diagnosis may be made clinically or at necropsy. Clinical diagnosis of cerebral infarction is not without error. HEASMAN and LIPWORTH12 found that a clinical diagnosis of "cerebral thrombosis" accorded with the post-mortem diagnosis in 45% of cases; in 11% cerebral or subarachnoid hxmor-
diagnosed at post-mortem, and in another 9% myocardial infarction was diagnosed. Before the xtiology of cerebral infarction can be properly investigated a uniform nomenclature and a common set of diagnostic criteria need to be rhage
was
defined. In the U.S.A. the National Institute of Neurological and Communicative Disorders and Stroke13 has attempted this, but its 52-page document seems too complex for widespread use. The classification system suggested by CAPILDEO and his colleaguesl4 seems more promising, but they have not specified the precise criteria by which cerebral infarction, cerebral hxmorrhage, and other forms of stroke should be diagnosed. Standard criteria, like those used to define myocardial infarction, would be useful. Emphasis should be given to the development of diagnostic criteria which balance the need to avoid misclassification errors with the need to maintain simplicity. The studies of HABERMAN et al. and their predecessors 1,3,5 are persuasive in challenging the widely held belief that cerebral infarction and myocardial infarction have a common cause. Because many of their arguments are based on mortality statistics, which are indirect and subject to diagnostic error, it is unwise to draw any firm conclusions from their work at this stage. However, these findings cannot be disregarded. It is clear that remarkably little is known about the factors which increase the risk of cerebral infarction or other forms of stroke, despite their being a very common cause of death. All too often stroke is investigated as a subsidiary analysis in a larger study of myocardial infarction. As the surveys were designed primarily to elucidate the risk factors associated with myocardial infarction and the analyses concentrated on the relationship of cerebral infarction with factors known to affect myocardial infarction risk, it is not surprising that they have been unrewarding with respect to Advisory Council for the National Institute of Neurological and Communicative Disorders and Stroke. Stroke, 1975, 6, 565. 14. Capildeo, R, Haberman, S., Rose, F. C. Br med. J. 1977, ii, 1578.
stroke.9 Surely it is time to look afresh at cerebral infarction-and to stop regarding it as a mere variant
of myocardial infarction. The Infant-food
Industry
IN those parts of the world which lack wealth and natural resources and where populations are often dense, breast-feeding of infants has become less common over the past thirty years. That is a striking misuse of one natural resource which many people could use to their benefit - namely, breast milk. The effect of this change in infant feeding has been keenly debated. The balance of judgment is that it has not been beneficial: as far as the evidence goes, diarrhoea and marasmus have not abated in artificially fed babies; biological child-spacing, as a consequence of lactation amenorrhoea, has come to have less influence on population control; and the cost to families and to nations who have bought the replacements for breast milk has been substantial. The causes of the decline in breast-feeding in Africa, Asia, and elsewhere include urbanisation and all that it entails (especially the desire of mothers to work and the aspiration towards Western styles); and the health services in many lands are ill designed to meet local needs when they offer maternity units which separate the mother from the newborn and when health professionals are inadequate in numbers and in education. Moreover, the industry which supplies artificial food for infants has long been active in encouraging the consumption of its products, often in circumstances where it is hard for a mother to prepare a bottle cleanly or for her family to afford the cost of filling it with nutritionally adequate contents.
From this story has sprung an argument which has concentrated largely on the promotional activities of the infant-food industry in the developing world. The Lancet has been among those who have criticised the industry,I which, after an initial response of shock and incredulity, formed the International Council of Infant Food Industries, a body which seeks to obtain recognition as a self-regulator of the industry. We invited the Council to set out its objectives in our columns; and its statement appears this week on p. 1250. With several large international companies not yet members, the Council has some way to go and its muscle as a deterrent to unacceptable promotional practices may prove feeble in the face of commercial pressures. But we believe that its offer of cooperation with scientists and academic institutes, with the international health agencies, and with governments should be given a hearing - as a welcome alternative to the wounding exchanges which have dominated this scene.
13.
15. Rose, G. A. Bull. Wld Hlth Org. 1962, 27, 645 1. See Lancet, 1976, ii, 503, ibid. 1977, i, 1067
1241
industry has reacted in other ways to the strictures heaped upon it. Less emphasis has certainly been put on "milk nurses", whose talks to mothers often seemed to discourage breast-feeding; and the aim is now said to be to "complete not compete" in infant feeding, though the assurance that the industry now works through the health profession (and with its express approval) carries small weight in countries where professionals are so few and poorly trained in nutrition. It remains to emerge how far these principles, which the industry is now more vigorously espousing, are convertible The
into actions which can surmount the dilemma of a conflict between profit making and public health. Meanwhile, the medical profession has its own path to tread. If programmes to support breastfeeding are to be convincingly encouraged and extended, more data must be gathered on the effects of different factors in different places, particularly the influences of education at all levels. For babies who must be bottle-fed, the need is for a non-advertised low-cost formula; and, for weaning, cheap multimix foods must be provided. Nutrition, of mothers as well as infants, is a deplorably neglected subject - in medical schools and in the councils of governments. It is clearly not a matter for further recrimination and litigation. If the infant-food industry is to find its proper role, it must stand up for I.C.I.F.I. and engage in a reasoned debate. If it fails to grasp this opportunity for reform, it will be subject to further criticism and calumny; and some governments may take action to exclude proprietary infant foods when they realise that they and their peoples could spend what money they have more wisely.
CARDIAC DEATH IN DIABETES ABOUT
50% of diabetic patients die from coronary
heart-disease,’ nearly double the rate in non-diabetics. This high mortality is accounted for not only by the frequency of coronary disease in diabetics but also by its severity. Acute myocardial infarction carries a poor early prognosis,2,3 and only half the patients admitted to hospital are alive after 12 months.4 The aetiology of heart-disease in diabetics is complex5-7-with probable contributions from hypertension, hyperlipidasmia, obesity, coagulation disorders, and microangiopathy. Myocardial infarction tends to present atypically in diabetics. About a third of patients have little or no pain,4,8 but rather slip insidiously into cardiac failure, shock, ketoacidosis, or even lactic acidosis. This painlessness has been attributed to autonomic neuropathy, but until 1. 2
Bradley, R. F. in Joslin’s Diabetes Mellitus (edited by A. Marble, P. White, R. F. Bradley, L. P. Krall), p. 417. Philadelphia, 1971. Soler, N. G., Pentecost, B. L., Bennett, M. A., Fitzgerald, M. G., Lamb, P., Malins, J. M. Lancet, 1974, i, 475.
3. 4.
Harrower, A. D. B., Clarke, B. F. Br med. J. 1976, i, 126. Soler, N. G., Bennett, M. A., Pentocost, B. L., Fitzgerald, M. G., Malins, J M. Q. Jl Med. 1975, 44, 125. 5. Harrower, A. D. B. Br. J. clin. Pract. 1977, 31, 47. 6. Page, M. M., Watkins, P. J. Clins Endocr. Metab. 1977, 6, 377. 7. Jarrett, J. ibid. p. 389. 8. Bradley, R. F., Schonfield, A. Geriatrics, 1962,17, 322.
there has been no evidence for this theory. Faeral. have now provided some such evidence. They did detailed histological work on the hearts of five diabetics who had just died with painless infarction, and on the hearts of similar-sized groups of diabetics and nondiabetics both with painful infarction and without infarction. They found degeneration and loss of sympathetic and parasympathetic fibres in all the cases of painless infarction but in none of the control groups. Three patients in the study group had other evidence of neuropathy and three had retinopathy (information was not available in one patient), but these complications were also common in the control diabetics. Several questions arise. Why was there no histological evidence of neuropathy in the hearts of the five diabetics who had no myocardial infarction, despite clinical evidence of neuropathy in four of them? It is surprising too that neuronal degeneration, often severe, was found in the study group, yet not even minor abnormalities were seen in the control groups. If neuropathy is the cause of painless myocardial infarction in diabetics, isolated degeneration of afferent cardiac nerves must be common, although other evidence of autonomic neuropathy affecting the cardiovascular system is uncommon. (Impotence may be a similar isolated manifestation of autonomic neuropathy in many male diabetics, and it is interesting that Faerman et al. found morphological similarities between the nerve lesions in the heart and abnormalities which they had previously found in the urinary bladder and corpora cavernosa of impotent diabetics.) The occurrence of painless infarction in non-diabetics also needs explanation and further histological studies of cardiac nerves are needed in both diabetics and non-diabetics. Cardiac enlargement and failure may arise in diabetics in the absence of overt myocardial infarction or other evidence of coronary heart-disease. This cardiomyopathic picture is often due to multiple infarcts caused by extensive occlusion of major coronary arteries, IO but there is increasing evidence that microangiopathy may also be responsible. Measurement of systolic time-intervals" and echocardiographyl2 suggests that subclinical myocardial dysfunction is very common in diabetics with other evidence of small-vessel disease. A histological investigation of cardiac microvascular disease was recently presented to the American Heart Association by S. Zoneralch. 13 Abnormalities of small intramural arteries were found in 36 out of 50 diabetics as against 9 of 32 controls. Half of the diabetics with small-vessel disease also showed disease of the larger coronary arteries, and nearly two-thirds of the diabetics had enlarged hearts and extensive myocardial fibrosis. Small vessels close to the sinus and atrioventricular nodes were often involved, and this may explain the low heart-rates which have been found after autonomic blockade in diabetics with autonomic neuropathy.14 Extensive vascular occlusion may well have an important role in myocardial infarction without pain, both in diabetics and in non-diabetics, and perhaps degeneration of
lately
man et
9.
Faerman, I., Faccio, E., Milei, J., Nunez, R., Jadinsky, M., Fox, D., Rapaport, M. Diabetes, 1977, 26, 1147. 10. Dash, H., Johnson, R. A., Dinsmore, R. E., Francis, C. K. Harthorne, J. W. Br. Heart J. 1977, 39, 740. 11. Seneviratne, B. I. B. Br. med. J. 1977, i, 1444. 12. Sanderson, J. E., Brown, D. J., Rivellese, A., Kohner, E. ibid. 1978, i, 404. 13. Cited in Diabetes Outlook, March, 1978. 14. Lloyd-Mostyn, R. H., Watkins, P. J. Br. med. J. 1975, iii, 15.
