- Email: [email protected]
CARE OF THE SUBNORMAL
33 acid phenylalanine. Equally strikingly, Crick and his colleagues2 in this country have produced good evidence that the basic unit of the code, which codes one aminoacid, is a sequence of three of the four possible bases. The evidence for a basic unit of three comes from the study of multiple mutations of one gene of a bacteriophage which attacks Escherichia coli. These mutations are thought to involve the addition or deletion of a base. The addition of one base destroys the function of the gene, the addition of a second leaves the gene still functionless, but the addition of a third largely restores the function of the gene. If the normal sequence is, say, ABC, ABC, ... , the effect of adding one base is to give MAB, CAB, CAB, ... , of adding two is to give MMA, BCA, BCA, ... , but of adding three is to give MMM, ABC, ABC,... when most of the gene is restored to the original ABC sequence.
Crick and his colleagues would therefore conclude from the findings of Nirenberg and Matthaei that a sequence of three uracil bases is the code for the aminoacid phenylalanine. Since other R.N.A. molecules with a known sequence of bases may be synthesised, it is reasonable to expect that further in-vitro experiments of this kind will make it possible to work out more of the code. It is, however, to be expected, since a code of three bases out of four gives 64 different possibilities, that the code is " degenerate " in the sense that one particular aminoacid can be coded by several triplets of genes. Within the limits of this freedom it is probable that the code will be the same in all living organisms, from viruses to man. Thus, work of this kind heralds the day when the mutations responsible for, say, fragilitas ossium or hxmophilia can be interpreted in terms of an alteration in a triplet of bases and perhaps even be artificially corrected.
CORONARY INSUFFICIENCY
PATIENTS with coronary-artery disease present with a wide spectrum of clinical syndromes ranging from angina
provoked only by strenuous exertion to massive myocardial infarction with early electrocardiographic abnormality. Between these extremes lie many intermediate syndromes.33 Careful serial observations are commonly necessary to confirm major infarction in patients with T-wave changes or a level of serum-glutamic-oxaloacetic-transaminase slightly raised only after some days. One inquiry showed that in only 42% of patients with myocardial infarction admitted to hospital was definite electrocardiographic evidence detectable within forty-eight hours.4 Since 19375 another intermediate syndrome of " coronary insufficiency has been increasingly recognised. In such cases the coronary blood-flow is impeded, usually suddenly, by thrombosis. The supply of blood suffices to prevent cell necrosis but does not provide for the metabolic needs of the myocardium at rest. The patient has lengthy attacks of rest pain lasting ten to thirty minutes, as well as angina provoked by slight exertion, excitement, food, or cold. No objective evidence of infarction is found; and the temperature, erythrocytesedimentation rate, leucocyte-count, and serum-glutamic"
oxaloacetic-transaminase level are normal. Electroevidence of ST cardiographic ischeemia-usually depression Crick, F. H. C., Barnett, L., Brenner, S., Watts-Tobin, R. J. Nature, Lond. 1961, 192, 1227. 3. Vakil, R. J. Circulation, 1961, 24, 557. 4. Phear, D., Stirland, R. Lancet, 1957, ii, 270. 5. Sampson, J. J., Eliaser, M. Amer. Heart J. 1937, 13, 675.
2.
-is a constant finding.6 About 10% of patients with ischsemic heart-disease present with coronary insufficiency; and in half these cases this precarious state persists for two months or longer.7 CARE OF THE SUBNORMAL
THOUGH we have long accepted that men are but children of a larger growth, we have only lately realised that it is equally true that many defectives are but children of a slower growth. Because the defective learns so slowly, people have been misled into thinking that he does not learn at all. Some ten years ago, however, Tizard8 and O’Connor showed that given time and encouragement many defectives could master simple tasks and achieve a proficiency and output not much inferior to normal people. Too often the defective’s natural abilities are further curtailed by his environment. As Dr. Clarke points out on p. 40, because the defective is a slow learner he needs more experience than the normal child. Instead he often gets less. Anxious parents are overprotective and life in an institution is likely to cramp his activities, independence, and initiative. Tizard9 has lately described a small experimental unit which offered the older handicapped child the ordered but free regime of a nursery school. After some months in this permissive and affectionate background a group of maladjusted imbecile children improved notably in social and emotional behaviour, intelligence, and speech. It seems, therefore, that the defective, far from being indifferent to his surroundings, is peculiarly dependent on environment. The Mental Health Act, with its emphasis on community care, gives us a chance to apply this new approach; and in his survey]Oof mental subnormality and its future care Dr. F. M. Martin suggests that the small residential unit, in or near an urban centre, would offer many of the advantages of family life. He believes that units of this kind need not be much more expensive to run, per child, than large overcrowded colonies, and would certainly be easier to staff. The form (or forms) of care which we provide for these people merit careful study; for, though it is difficult to assess the prevalence of mental defect in the population, there is no doubt that the number of mental defectives is increasing. Their chances of survival and of longevity have greatly improved. Many are likely to outlive their parents and become the wards of the community. In fact the admission-rate to institutions has been rising steadily (2869 in 1951, 4831 in 1959), and most of these new residents are middle-aged or elderly defectives who have been living in the community with parents or relatives who have died. Despite this increase there is an unsatisfied demand for places, and at the end of 1959 some 6000 cases, half of them classified as urgent, were on hospital waiting-lists. Though the interpretation of national
statistics, as we are always learning to our cost, must be speculative, Dr. Martin considers that there is already a clear case for extending and reinforcing community alternative to institutional care wherever Besides the small residential units mentioned possible. like to see families who are looking after he would above, services
6. 7. 8. 9. 10.
as an
Scherf, D. N.Y. St. J. Med. 1947, 47, 2420. Wood, P. Brit. med. J. 1961, i, 1779. Tizard, J., O’Connor, N. Lancet, 1952, ii, 620. Tizard, J. Brit. med. J. 1960, i, 1041. Martin, F. M. Mental Subnormality and Community Care. Planning, 1961, 28, no. 457. 3s. 6d. (from P.E.P., 16, Queen Anne’s Gate, London, S.W.1).
34
defective in their own home offered more help in the form of genetic counselling, nursery schools, training centres, and short-stay units.
a
Responsibility for providing the training and occupation centres which are a necessary buttress to extramural care rests chiefly with the local authorities, and Dr. Martin reports that almost all have plans for extending this part of their work and that the supply of places is likely to match the demand before too long. But the authorities
unreasonably, more hesitant about providing residential accommodation, for at present there is some uncertainty about its purpose. Is it needed for people who are at present living in the community but need more support, or for discharged patients ? Should it be a permanent shelter within the community or should it be a bridge towards an independent life in the community ? Dr. Martin modestly ends his descriptive survey with a plea for experiment as the best form of social research. He would like to see a trial of an integrated mental subnormality service for a city which might perhaps include an ascertainment service, small short-term and long-term residential units, a variety of training and industrial centres, and a family advisory service. He adds a warning that an administrative innovation does not qualify as an experiment unless provision is made for an objective assessment of its results. are, not
COR PULMONALE
As a working definition of chronic cor pulmonale, there is much to be said for the one adopted by the W.H.O. expert committee —namely, " hypertrophy of the right ventricle, resulting from diseases affecting the function and/or structure of the lung, except where these pulmonary alterations are the result of diseases that primarily affect the left side of the heart or of congenital heart disease ". Today it hardly seems necessary to remind British readers that the condition is important and relatively common, since we have now become more aware of the damage done in this country by chronic bronchitis. But general recognition of its importance is comparatively recent, and the International Classification of Diseases relegates it to the residual category of " unspecified disease of the heart ". The committee recommend that diseases causing chronic cor pulmonale should be conventionally divided into those groups primarily affecting the air-passages of the lung and alveoli, those affecting movements of the thoracic cage, and those affecting the pulmonary vasculature. In addition they suggest an alternative shorter classification, in which the commonest diseases have greatest prominence (bronchitis and/or emphysema heading the list) and a special category is given to thromboembolic diseases and to primary or idiopathic
pulmonary hypertension. Four main alterations of
respiratory function can now recognised: (1) obstructive ventilatory impairment,
be where there is obstruction to airflow in the tracheobronchial tree; (2) restrictive ventilatory impairment, where ventilatory capacity is reduced without obstruction to airflow; (3) impairment in pulmonary gas diffusion between alveoli and pulmonary capillaries; and (4) reduction in ventilation/perfusion ratio, some of the blood 1. Tech. Rep. Wld Hlth Org. no. 213. 1961. H.M. Stationery Office at 1s. 9d.)
Pp. 35.
(Obtainable from
passing through areas of diminished or absent ventilation. The most widely used simple tests recommended for assessing ventilatory function are measurement of the forced expiratory volume in one second (F.E.v.) and the vital capacity (v.c.). The F.E.V., expressed as a percentage of the v.c., helps to distinguish between obstructive and restrictive impairment. Alveolar capillary gaseous exchange is harder to measure. Reduction in the ventilation/ perfusion ratio results in the blood being depleted of oxygen though its content of carbon dioxide remains normal and estimation of both these blood-gas tensions gives useful information. Cardiac catheterisation, though seldom needed to establish the diagnosis, has thrown much light on the hsemodynamic changes. The greater pulmonary vascular resistance, which obliges the right ventricle to do more work, may be due to obstruction of the pulmonary bloodvessels (as in thromboembolism), to reduction in the size of the pulmonary capillary bed (as in emphysema or lung resection), or to functional changes reducing the calibre of the pulmonary vessels. In bronchitis these functional changes evidently do much to determine the pulmonary vascular resistance as is shown by the episodic nature of the pulmonary hypertension, which may sometimes normal or near-normal levels after recovery from heart-failure. Hypoxaemia seems to be one of the factors related to functional changes, but the role of other factors, including carbon-dioxide tension, alterations in bloodflow and blood-volume, nervous stimuli, and hormonal influences, remains to be established. In more advanced cases of chronic cor pulmonale, myocardial ischaemia resulting from deficiency of oxygen in the blood may put a further burden on an already failing heart. Clinical recognition of cor pulmonale is not always easy, especially in the initial stages when breathlessness due to chronic chest disease may gradually merge into breathlessness due to associated heart-failure. Signs of right ventricular hypertrophy may be largely obscured by the distended overlying lung, a right ventricular thrust being palpable only in the epigastrium. When heartfailure supervenes-with cyanosis, raised jugular venous pressure, an enlarged liver, and cedema-the diagnosis is usually obvious, especially where there is a clear history of longstanding respiratory disease. Primary pulmonary vascular disease, on the other hand, such as thromboembolic pulmonary hypertension, may present a rather different picture. The patient may have no symptoms until syncope and exertional dyspnoea supervene; but the signs of right ventricular hypertrophy are easier to recognise, since they are not obscured by an overdistended revert to
lung. The radiological appearances vary with the cause of chronic cor pulmonale. There may be evidence of emphysema with enlarged main pulmonary arteries and relatively clear lung fields, and with some enlargement also of the right ventricle and right atrium. Where the disease is primarily of the lung vasculature, enlargement of the main pulmonary artery and its primary branches may sometimes be greater than in other forms of cor pulmonale. Electrocardiography, although usually helpful in the diagnosis, may be equivocal where there is right ventricular hypertrophy, and its interpretation is especially difficult where the left heart is also enlarged-e.g., because of systemic hypertension. Treatment consists essentially in energetic treatment of the flare-up of bronchitis and of heart-failure. The
Crick and his colleagues would therefore conclude from the findings of Nirenberg and Matthaei that a sequence of three uracil bases is the code for the aminoacid phenylalanine. Since other R.N.A. molecules with a known sequence of bases may be synthesised, it is reasonable to expect that further in-vitro experiments of this kind will make it possible to work out more of the code. It is, however, to be expected, since a code of three bases out of four gives 64 different possibilities, that the code is " degenerate " in the sense that one particular aminoacid can be coded by several triplets of genes. Within the limits of this freedom it is probable that the code will be the same in all living organisms, from viruses to man. Thus, work of this kind heralds the day when the mutations responsible for, say, fragilitas ossium or hxmophilia can be interpreted in terms of an alteration in a triplet of bases and perhaps even be artificially corrected.
CORONARY INSUFFICIENCY
PATIENTS with coronary-artery disease present with a wide spectrum of clinical syndromes ranging from angina
provoked only by strenuous exertion to massive myocardial infarction with early electrocardiographic abnormality. Between these extremes lie many intermediate syndromes.33 Careful serial observations are commonly necessary to confirm major infarction in patients with T-wave changes or a level of serum-glutamic-oxaloacetic-transaminase slightly raised only after some days. One inquiry showed that in only 42% of patients with myocardial infarction admitted to hospital was definite electrocardiographic evidence detectable within forty-eight hours.4 Since 19375 another intermediate syndrome of " coronary insufficiency has been increasingly recognised. In such cases the coronary blood-flow is impeded, usually suddenly, by thrombosis. The supply of blood suffices to prevent cell necrosis but does not provide for the metabolic needs of the myocardium at rest. The patient has lengthy attacks of rest pain lasting ten to thirty minutes, as well as angina provoked by slight exertion, excitement, food, or cold. No objective evidence of infarction is found; and the temperature, erythrocytesedimentation rate, leucocyte-count, and serum-glutamic"
oxaloacetic-transaminase level are normal. Electroevidence of ST cardiographic ischeemia-usually depression Crick, F. H. C., Barnett, L., Brenner, S., Watts-Tobin, R. J. Nature, Lond. 1961, 192, 1227. 3. Vakil, R. J. Circulation, 1961, 24, 557. 4. Phear, D., Stirland, R. Lancet, 1957, ii, 270. 5. Sampson, J. J., Eliaser, M. Amer. Heart J. 1937, 13, 675.
2.
-is a constant finding.6 About 10% of patients with ischsemic heart-disease present with coronary insufficiency; and in half these cases this precarious state persists for two months or longer.7 CARE OF THE SUBNORMAL
THOUGH we have long accepted that men are but children of a larger growth, we have only lately realised that it is equally true that many defectives are but children of a slower growth. Because the defective learns so slowly, people have been misled into thinking that he does not learn at all. Some ten years ago, however, Tizard8 and O’Connor showed that given time and encouragement many defectives could master simple tasks and achieve a proficiency and output not much inferior to normal people. Too often the defective’s natural abilities are further curtailed by his environment. As Dr. Clarke points out on p. 40, because the defective is a slow learner he needs more experience than the normal child. Instead he often gets less. Anxious parents are overprotective and life in an institution is likely to cramp his activities, independence, and initiative. Tizard9 has lately described a small experimental unit which offered the older handicapped child the ordered but free regime of a nursery school. After some months in this permissive and affectionate background a group of maladjusted imbecile children improved notably in social and emotional behaviour, intelligence, and speech. It seems, therefore, that the defective, far from being indifferent to his surroundings, is peculiarly dependent on environment. The Mental Health Act, with its emphasis on community care, gives us a chance to apply this new approach; and in his survey]Oof mental subnormality and its future care Dr. F. M. Martin suggests that the small residential unit, in or near an urban centre, would offer many of the advantages of family life. He believes that units of this kind need not be much more expensive to run, per child, than large overcrowded colonies, and would certainly be easier to staff. The form (or forms) of care which we provide for these people merit careful study; for, though it is difficult to assess the prevalence of mental defect in the population, there is no doubt that the number of mental defectives is increasing. Their chances of survival and of longevity have greatly improved. Many are likely to outlive their parents and become the wards of the community. In fact the admission-rate to institutions has been rising steadily (2869 in 1951, 4831 in 1959), and most of these new residents are middle-aged or elderly defectives who have been living in the community with parents or relatives who have died. Despite this increase there is an unsatisfied demand for places, and at the end of 1959 some 6000 cases, half of them classified as urgent, were on hospital waiting-lists. Though the interpretation of national
statistics, as we are always learning to our cost, must be speculative, Dr. Martin considers that there is already a clear case for extending and reinforcing community alternative to institutional care wherever Besides the small residential units mentioned possible. like to see families who are looking after he would above, services
6. 7. 8. 9. 10.
as an
Scherf, D. N.Y. St. J. Med. 1947, 47, 2420. Wood, P. Brit. med. J. 1961, i, 1779. Tizard, J., O’Connor, N. Lancet, 1952, ii, 620. Tizard, J. Brit. med. J. 1960, i, 1041. Martin, F. M. Mental Subnormality and Community Care. Planning, 1961, 28, no. 457. 3s. 6d. (from P.E.P., 16, Queen Anne’s Gate, London, S.W.1).
34
defective in their own home offered more help in the form of genetic counselling, nursery schools, training centres, and short-stay units.
a
Responsibility for providing the training and occupation centres which are a necessary buttress to extramural care rests chiefly with the local authorities, and Dr. Martin reports that almost all have plans for extending this part of their work and that the supply of places is likely to match the demand before too long. But the authorities
unreasonably, more hesitant about providing residential accommodation, for at present there is some uncertainty about its purpose. Is it needed for people who are at present living in the community but need more support, or for discharged patients ? Should it be a permanent shelter within the community or should it be a bridge towards an independent life in the community ? Dr. Martin modestly ends his descriptive survey with a plea for experiment as the best form of social research. He would like to see a trial of an integrated mental subnormality service for a city which might perhaps include an ascertainment service, small short-term and long-term residential units, a variety of training and industrial centres, and a family advisory service. He adds a warning that an administrative innovation does not qualify as an experiment unless provision is made for an objective assessment of its results. are, not
COR PULMONALE
As a working definition of chronic cor pulmonale, there is much to be said for the one adopted by the W.H.O. expert committee —namely, " hypertrophy of the right ventricle, resulting from diseases affecting the function and/or structure of the lung, except where these pulmonary alterations are the result of diseases that primarily affect the left side of the heart or of congenital heart disease ". Today it hardly seems necessary to remind British readers that the condition is important and relatively common, since we have now become more aware of the damage done in this country by chronic bronchitis. But general recognition of its importance is comparatively recent, and the International Classification of Diseases relegates it to the residual category of " unspecified disease of the heart ". The committee recommend that diseases causing chronic cor pulmonale should be conventionally divided into those groups primarily affecting the air-passages of the lung and alveoli, those affecting movements of the thoracic cage, and those affecting the pulmonary vasculature. In addition they suggest an alternative shorter classification, in which the commonest diseases have greatest prominence (bronchitis and/or emphysema heading the list) and a special category is given to thromboembolic diseases and to primary or idiopathic
pulmonary hypertension. Four main alterations of
respiratory function can now recognised: (1) obstructive ventilatory impairment,
be where there is obstruction to airflow in the tracheobronchial tree; (2) restrictive ventilatory impairment, where ventilatory capacity is reduced without obstruction to airflow; (3) impairment in pulmonary gas diffusion between alveoli and pulmonary capillaries; and (4) reduction in ventilation/perfusion ratio, some of the blood 1. Tech. Rep. Wld Hlth Org. no. 213. 1961. H.M. Stationery Office at 1s. 9d.)
Pp. 35.
(Obtainable from
passing through areas of diminished or absent ventilation. The most widely used simple tests recommended for assessing ventilatory function are measurement of the forced expiratory volume in one second (F.E.v.) and the vital capacity (v.c.). The F.E.V., expressed as a percentage of the v.c., helps to distinguish between obstructive and restrictive impairment. Alveolar capillary gaseous exchange is harder to measure. Reduction in the ventilation/ perfusion ratio results in the blood being depleted of oxygen though its content of carbon dioxide remains normal and estimation of both these blood-gas tensions gives useful information. Cardiac catheterisation, though seldom needed to establish the diagnosis, has thrown much light on the hsemodynamic changes. The greater pulmonary vascular resistance, which obliges the right ventricle to do more work, may be due to obstruction of the pulmonary bloodvessels (as in thromboembolism), to reduction in the size of the pulmonary capillary bed (as in emphysema or lung resection), or to functional changes reducing the calibre of the pulmonary vessels. In bronchitis these functional changes evidently do much to determine the pulmonary vascular resistance as is shown by the episodic nature of the pulmonary hypertension, which may sometimes normal or near-normal levels after recovery from heart-failure. Hypoxaemia seems to be one of the factors related to functional changes, but the role of other factors, including carbon-dioxide tension, alterations in bloodflow and blood-volume, nervous stimuli, and hormonal influences, remains to be established. In more advanced cases of chronic cor pulmonale, myocardial ischaemia resulting from deficiency of oxygen in the blood may put a further burden on an already failing heart. Clinical recognition of cor pulmonale is not always easy, especially in the initial stages when breathlessness due to chronic chest disease may gradually merge into breathlessness due to associated heart-failure. Signs of right ventricular hypertrophy may be largely obscured by the distended overlying lung, a right ventricular thrust being palpable only in the epigastrium. When heartfailure supervenes-with cyanosis, raised jugular venous pressure, an enlarged liver, and cedema-the diagnosis is usually obvious, especially where there is a clear history of longstanding respiratory disease. Primary pulmonary vascular disease, on the other hand, such as thromboembolic pulmonary hypertension, may present a rather different picture. The patient may have no symptoms until syncope and exertional dyspnoea supervene; but the signs of right ventricular hypertrophy are easier to recognise, since they are not obscured by an overdistended revert to
lung. The radiological appearances vary with the cause of chronic cor pulmonale. There may be evidence of emphysema with enlarged main pulmonary arteries and relatively clear lung fields, and with some enlargement also of the right ventricle and right atrium. Where the disease is primarily of the lung vasculature, enlargement of the main pulmonary artery and its primary branches may sometimes be greater than in other forms of cor pulmonale. Electrocardiography, although usually helpful in the diagnosis, may be equivocal where there is right ventricular hypertrophy, and its interpretation is especially difficult where the left heart is also enlarged-e.g., because of systemic hypertension. Treatment consists essentially in energetic treatment of the flare-up of bronchitis and of heart-failure. The