BRITISH MEDICAL JOURNAL
Britain the NHS has a monopoly of medical care and many doctors are individual monopoly providers of it. In an ideal society the patient and the doctor, both supplied with the latest knowledge, discuss the possibilities and either agree-in which case the agreed treatment is given-or disagree, in which case the patient goes out to find another doctor. Here in Britain, however, often there is no other doctor, and conflict is inevitable. This is seen in the angry protests by women who want to have their babies at home but cannot find an obstetrician to go along with their wishes; and in the most extreme example the conflict between patients' expectations and doctors' judgments has led to the growth of a private sector to provide termination of pregnancy outside the NHS. We are not arguing that every patient must accept his or her doctor's advice uncritically; but doctors will object to the DHSS telling their patients what that advice should be. There is an important difference between patients being encouraged by the DHSS to be vaccinated or to stop smoking and the Department's attempting to give more detailed advice on the treatment or prevention of illness. Doctors are not technicians paid by the NHS to hand out treatment decided by expert committees: they are professionals who are trained to make an assessment in an individual case-advice that the patient should then be free to accept or reject. 2
1173
5 NOVEMBER 1977
Parliamentary Commissioner for Administration, Sixth Report: Whooping Couigh Vaccination. London, HMSO, 1977. The Timsles, 28 October 1977. The Guiardian, 28 October 1977.
Vertigo in children Vertigo is not common in childhood, and because it is a subjective phenomenon and the younger child cannot describe what he feels it may present difficulties in diagnosis-indeed, the fact that the child is experiencing vertigo may not be recognised. Standard textbooks of paediatrics provide little help: one such, of over 2000 pages, does not include the word vertigo in the index. A recent American study of 50 children with vertigo' indicated that 25 were having "seizures," presumably epilepsy, mainly arising from the temporal lobe; five each were diagnosed as having vestibular neuronitis, migraine, or psychological causes; in four the symptoms were sequelae of trauma and in three of meningitis; two had benign paroxysmal vertigo; and one had congenital deafness. Other causes, not found in this series, include hypoglycaemia, cerebral lesions, multiple sclerosis, and the effect of drugs. Moreover, vertigo may be confused with an impending faint. The first essential towards the diagnosis must be a detailed history. In a young child a faint would be rare. In an older child fainting is usually due to prolonged standing, as in school assembly, or a sudden change in posture. A family history of fits, or the loss of consciousness with convulsive movements, may suggest epilepsy. Vestibular neuronitis occurs usually a few days after an upper respiratory tract infection, with recurring attacks of vertigo without abnormal neurological signs, but with abnormal labyrinthine responses to hot and cold; it may be difficult to distinguish from other causes of sudden vertigo. Epidemic vertigo is also thought to be due to a virus: there is a sudden onset with nausea and vomiting, lasting a few days, often with nystagmus and diplopia, and
the illness may infect others. In the "acute cerebellar syndrome," described by Blau and Sheehan2 in children aged 1-4 years, symptoms occur 7 to 10 days after an upper respiratory tract infection, with acute ataxia and vertigo reaching a maximum in 24 to 72 hours, and recovery in days or weeks; the cerebrospinal fluid is usually normal. This too is thought to be due to a viral infection. Vertigo is a feature of labyrinthitis when this is a rare complication of mumps. Benign paroxysmal vertigo3 4 iS important because it may readily be confused with epilepsy, but a distinguishing feature is the absence of loss of consciousness. It occurs especially in children aged 1-3 years; there are multiple brief episodes, lasting up to 30 seconds, of sudden onset without warning, in which the child cries for help, is terrified and ataxic or falls or clings to his mother, may sweat, may vomit, may have nystagmus, and is normal after the attack. Attacks recur in days or weeks; there are commonly one to four attacks a month; they cease in four months to four years. The cerebrospinal fluid is normal, but there is an abnormal response to the caloric stimulation test.5 Vertigo may be a symptom of hypoglycaemia or a premonitory symptom of an attack of migraine. It may be an early symptom of multiple sclerosis in children.6 Numerous drugs may cause vertigo: the long list includes acetazolamide, amitriptyline, antihistamines, carbamazepine, clonazepam, clonidine, colistin, diazepam, dicyclomine, ethosuccimide, fenfluramine, gentamicin, griseofluvin, imipramine, indomethacin, isoniazid, kanamycin, meprobamate, minicycline, nalidixic acid, paromomycin, pethidine, phenytoin, phenothiazine, phensuccimide, piperazine, polymyxin, primidone, salicylates, sulphonamides, thiazide diuretics, thiobendazole, and trimethoprim. Solvent sniffing is yet another cause. In the absence of abnormal neurological signs (apart from nystagmus) a careful history usually establishes the diagnosis. An electroencephalogram may be helpful if epilepsy is suspected, and the results of the caloric stimulation test may clinch a suspicion of labyrinthine disease. Treatment is often unsatisfactory and must depend on the cause. There is no good treatment for benign paroxysmal vertigo, though some authorities (possibly confusing the attacks with epilepsy) advocate the use of phenytoin. There is no treatment for epidemic vertigo or vestibular neuronitis. Fortunately all three conditions are self-limiting. Eviatar, L, and Eviatar, A, Pediatrics, 1977, 59, 833. Blau, M E, and Sheehan, J C, Neurology, 1958, 8, 538. 3Koenigsberger, M R, et al, Neurology, 1970, 20, 1108. 4Dunn, D W, and Snyder, H, American J7ournal of Diseases of Children, 1976, 130, 1099. 5 Rabe, E F, Current Problems in Pediatrics, 1974, 4, 3. 6 Molteni, R A, American Journal of Diseases of Children, 1977, 131, 553. 2
Thyroid disease and asthma From time to time a link has been noticed between thyroid disease and asthma amounting to more than a chance association. The most frequent reports have been of worsening of established asthma with the onset of hyperthyroidism, with subsequent improvement of the asthma when the euthyroid state is restored.14 The development of hypothyroidism may also result in improvement of coexistent asthma, which again becomes more resistant to treatment once effective thyroid replacement treatment has been given.4
1174
Most asthmatics affected by thyroid disease developed their respiratory symptoms in adult life, and both atopic and nonatopic patients may be affected. At one time atopic individuals were thought to show an increased incidence of hypothyroidism compared with normal people,5 but this belief was not confirmed by a controlled study.6 The nature of the biochemical link between asthma and thyroid disease remains obscure despite several possible mechanisms having been suggested. Thyroid hormones influence the concentration of intracellular cyclic adenosine 3'5'-monophosphate (cyclic AMP) and plasma catecholamine concentrations. Both sympathetic nervous activity and corticosteroid metabolism may also be affected in thyroid disease, and production of intracellular adenosine triphosphate (ATP) may be impaired in hyperthyroidism.7 Thyroxine increases the synthesis of adenyl cyclase, which would tend to increase the production of cyclic AMP from ATP.8 Settipane et al3 suggested that these effects of thyroxine might result in an overall decrease in cyclic AMP and so accentuate the defective adenyl cyclase activity reported in asthma.9 10 More recently it has been shown in practice that tissue and plasma concentrations of cyclic AMP are higher than normal in hyperthyroidism and are unaffected in hypothyroidism."1 Tissue responsiveness to catecholamines is increased by thyroid hormones and hyperthyroid patients are more sensitive than usual to catecholamines.12 In theory this should benefit patients with coexistent asthma, but in fact asthmatics tend to have worsening of their symptoms and increased side effects from sympathomimetic drugs at the onset of hyperthyroidism.3 The evidence on sympathetic nervous activity in thyroid disease is conflicting. Plasma catecholamine concentrations have been reported as reduced in hyperthyroidism,'3 but other studies have shown no significant changes in plasma adrenaline. Plasma noradrenaline concentrations, however, are normal in hyperthyroidism but raised in hypothyroidism, perhaps in an attempt to compensate for lack of thyroid hormone.14 Dopamine-f-hydroxylase (DBH), an enzyme catalysing the conversion of dopamine to noradrenaline, is decreased in hyperthyroidism but rises to normal with treatment15; and as DBH is derived mainly from sympathetic nerve endings without reuptake it is thought to be an accurate indicator of sympathetic nervous activity. Thyroxine increases the conversion of hydrocortisone to its inactive 11 -ketone metabolites and the rate of steroid reduction in the liver. In hyperthyroidism urinary excretion of conjugated steroid metabolites is increased but free cortisol concentrations in the plasma are reduced.16 The reverse effects are present in hypothyroidism. The onset of hyperthyroidism has certainly been found to increase the steroid requirements for treatment of established asthma.3 So possibly more than one of these mechanisms may be implicated in the effects of thyroid disease on coexistent asthma, but the effects on corticosteroid metabolism seem most likely to be relevant. Though hypothyroidism may be associated with some improvement in asthma, it would be inadvisable for the doctor to try to control asthma in patients with thyroid disease by deliberately producing hypothyroidism. Instead he should aim at restoring the euthyroid state with minimal treatment while controlling the asthma with the appropriate drugs. Feinberg, S M, in Allergy in Practice, p. 90. Chicago, Year Book Medical Publishers, 1944. Kasperlik-Zaluska, A, Gruzlica, 1968, 36, 581. 3 Settipane, G A, Schoenfeld, E, and Hamolsky, M W, Jfournal of Allergy and Clinical Immunology, 1972, 49, 348. I
2
BRITISH MEDICAL JOURNAL
5 NOVEMBER 1977
Bush, R K, Ehrlich, E N, and Reed, C E, Journal of Allergy and Clinical Immunology, 1977, 59, 398. Carlston, J A, Annals of Allergy, 1965, 23, 331. 6 Schwartz, H J, Annals of Allergy, 1966, 24, 234. 7 Satoyoshi, E, et al, Neurology, 1963, 13, 645. 8 Sutherland, E W, and Robison, G A, Pharmacological Reviews, 1966, 18, 145. 9 Logsdon, P J, Middleton, E, and Coffey, R G, Journal of Allergy and Clinical Immunology, 1972, 50, 45. 10 Parker, C W, Huber, M G, and Baumann, M L, Journal of Clinical Investigation, 1973, 52, 1342. "Karlberg, B E, Henriksson, K G, and Andersson, R G G, Journal of Clinical Endocrinology and Metabolism, 1974, 39, 96. 12 Murray, J F, and Kelly, J J, Annals of Internal Medicine, 1959, 51, 309. 13 Stoffer, S S, et al, Journal of Clinical Endocrinology and Metabolism, 1973, 36, 587. 14 Coulombe, P, Dussault, J H, and Walker, P, Metabolism, 1976, 25, 973. 15 Noth, R H, and Spaulding, S W, Journal of Clinical Endocrinology and Metabolism, 1974, 39, 614. 16 Hellman, L, et al, Journal of Clinical Endocrinology and Metabolism, 1961, 21, 1231.
Research priorities Six years after Lord Rothschild first made a casel 2 for the Government's commissioning research on a customercontractor basis the implications of his proposals are still being argued. He recommended a clearer separation of biomedical research (intended to increase knowledge) and health service research (intended to solve practical problems), and criticised the way that the Medical Research Council had financed work that "had and has no customer to commission and approve it." No matter how distinguished or intelligent scientists might be, said Rothschild, they could not be so well qualified to decide the nation's priorities for research expenditure. Returning to this theme in his Rock Carling lecture,3 Sir Andrew Watt Kay set out his considered objections to the Rothschild concept. It might be easy, he said, to obtain more applied science in areas such as defence, but it was naive to believe that the same was true of biology and medicine; and he questioned whether the development of applied research should or could be speeded up by the injection of more money or new management. Medicine differed from industry in one important way, said Sir Andrew. Much new knowledge and new technology tended to increase costs rather than reduce them. The practical import of any new discovery depended on the technological level at which it was made.4 High technology medicine implied understanding of the causation of a disease or at least identification of a specific remedy-antibiotics for bacterial infections, the prevention of rhesus haemolytic disease, the treatment of endocrine disorders with replacement hormones -and was characteristically easy to deliver, simple, and cheap. Here he disagreed with Professor McKeown5 6; Sir Andrew believed that the turn of the century would see a great increase in such specific remedies. Halfway technology medicine, in contrast, included the whole range of treatments given with varying success to minimise disability and suffering from diseases about which there was still insufficient knowledge. Replacement of diseased organs by transplants and prostheses, and operations to improve the blood supply to the heart affected by coronary artery disease, were obvious examples of the enormous costs of such an approach-and there were equally difficult problems of distribution and priority. The third level of technology was the substitute used by the medical profession when there was no means of altering the
Britain the NHS has a monopoly of medical care and many doctors are individual monopoly providers of it. In an ideal society the patient and the doctor, both supplied with the latest knowledge, discuss the possibilities and either agree-in which case the agreed treatment is given-or disagree, in which case the patient goes out to find another doctor. Here in Britain, however, often there is no other doctor, and conflict is inevitable. This is seen in the angry protests by women who want to have their babies at home but cannot find an obstetrician to go along with their wishes; and in the most extreme example the conflict between patients' expectations and doctors' judgments has led to the growth of a private sector to provide termination of pregnancy outside the NHS. We are not arguing that every patient must accept his or her doctor's advice uncritically; but doctors will object to the DHSS telling their patients what that advice should be. There is an important difference between patients being encouraged by the DHSS to be vaccinated or to stop smoking and the Department's attempting to give more detailed advice on the treatment or prevention of illness. Doctors are not technicians paid by the NHS to hand out treatment decided by expert committees: they are professionals who are trained to make an assessment in an individual case-advice that the patient should then be free to accept or reject. 2
1173
5 NOVEMBER 1977
Parliamentary Commissioner for Administration, Sixth Report: Whooping Couigh Vaccination. London, HMSO, 1977. The Timsles, 28 October 1977. The Guiardian, 28 October 1977.
Vertigo in children Vertigo is not common in childhood, and because it is a subjective phenomenon and the younger child cannot describe what he feels it may present difficulties in diagnosis-indeed, the fact that the child is experiencing vertigo may not be recognised. Standard textbooks of paediatrics provide little help: one such, of over 2000 pages, does not include the word vertigo in the index. A recent American study of 50 children with vertigo' indicated that 25 were having "seizures," presumably epilepsy, mainly arising from the temporal lobe; five each were diagnosed as having vestibular neuronitis, migraine, or psychological causes; in four the symptoms were sequelae of trauma and in three of meningitis; two had benign paroxysmal vertigo; and one had congenital deafness. Other causes, not found in this series, include hypoglycaemia, cerebral lesions, multiple sclerosis, and the effect of drugs. Moreover, vertigo may be confused with an impending faint. The first essential towards the diagnosis must be a detailed history. In a young child a faint would be rare. In an older child fainting is usually due to prolonged standing, as in school assembly, or a sudden change in posture. A family history of fits, or the loss of consciousness with convulsive movements, may suggest epilepsy. Vestibular neuronitis occurs usually a few days after an upper respiratory tract infection, with recurring attacks of vertigo without abnormal neurological signs, but with abnormal labyrinthine responses to hot and cold; it may be difficult to distinguish from other causes of sudden vertigo. Epidemic vertigo is also thought to be due to a virus: there is a sudden onset with nausea and vomiting, lasting a few days, often with nystagmus and diplopia, and
the illness may infect others. In the "acute cerebellar syndrome," described by Blau and Sheehan2 in children aged 1-4 years, symptoms occur 7 to 10 days after an upper respiratory tract infection, with acute ataxia and vertigo reaching a maximum in 24 to 72 hours, and recovery in days or weeks; the cerebrospinal fluid is usually normal. This too is thought to be due to a viral infection. Vertigo is a feature of labyrinthitis when this is a rare complication of mumps. Benign paroxysmal vertigo3 4 iS important because it may readily be confused with epilepsy, but a distinguishing feature is the absence of loss of consciousness. It occurs especially in children aged 1-3 years; there are multiple brief episodes, lasting up to 30 seconds, of sudden onset without warning, in which the child cries for help, is terrified and ataxic or falls or clings to his mother, may sweat, may vomit, may have nystagmus, and is normal after the attack. Attacks recur in days or weeks; there are commonly one to four attacks a month; they cease in four months to four years. The cerebrospinal fluid is normal, but there is an abnormal response to the caloric stimulation test.5 Vertigo may be a symptom of hypoglycaemia or a premonitory symptom of an attack of migraine. It may be an early symptom of multiple sclerosis in children.6 Numerous drugs may cause vertigo: the long list includes acetazolamide, amitriptyline, antihistamines, carbamazepine, clonazepam, clonidine, colistin, diazepam, dicyclomine, ethosuccimide, fenfluramine, gentamicin, griseofluvin, imipramine, indomethacin, isoniazid, kanamycin, meprobamate, minicycline, nalidixic acid, paromomycin, pethidine, phenytoin, phenothiazine, phensuccimide, piperazine, polymyxin, primidone, salicylates, sulphonamides, thiazide diuretics, thiobendazole, and trimethoprim. Solvent sniffing is yet another cause. In the absence of abnormal neurological signs (apart from nystagmus) a careful history usually establishes the diagnosis. An electroencephalogram may be helpful if epilepsy is suspected, and the results of the caloric stimulation test may clinch a suspicion of labyrinthine disease. Treatment is often unsatisfactory and must depend on the cause. There is no good treatment for benign paroxysmal vertigo, though some authorities (possibly confusing the attacks with epilepsy) advocate the use of phenytoin. There is no treatment for epidemic vertigo or vestibular neuronitis. Fortunately all three conditions are self-limiting. Eviatar, L, and Eviatar, A, Pediatrics, 1977, 59, 833. Blau, M E, and Sheehan, J C, Neurology, 1958, 8, 538. 3Koenigsberger, M R, et al, Neurology, 1970, 20, 1108. 4Dunn, D W, and Snyder, H, American J7ournal of Diseases of Children, 1976, 130, 1099. 5 Rabe, E F, Current Problems in Pediatrics, 1974, 4, 3. 6 Molteni, R A, American Journal of Diseases of Children, 1977, 131, 553. 2
Thyroid disease and asthma From time to time a link has been noticed between thyroid disease and asthma amounting to more than a chance association. The most frequent reports have been of worsening of established asthma with the onset of hyperthyroidism, with subsequent improvement of the asthma when the euthyroid state is restored.14 The development of hypothyroidism may also result in improvement of coexistent asthma, which again becomes more resistant to treatment once effective thyroid replacement treatment has been given.4
1174
Most asthmatics affected by thyroid disease developed their respiratory symptoms in adult life, and both atopic and nonatopic patients may be affected. At one time atopic individuals were thought to show an increased incidence of hypothyroidism compared with normal people,5 but this belief was not confirmed by a controlled study.6 The nature of the biochemical link between asthma and thyroid disease remains obscure despite several possible mechanisms having been suggested. Thyroid hormones influence the concentration of intracellular cyclic adenosine 3'5'-monophosphate (cyclic AMP) and plasma catecholamine concentrations. Both sympathetic nervous activity and corticosteroid metabolism may also be affected in thyroid disease, and production of intracellular adenosine triphosphate (ATP) may be impaired in hyperthyroidism.7 Thyroxine increases the synthesis of adenyl cyclase, which would tend to increase the production of cyclic AMP from ATP.8 Settipane et al3 suggested that these effects of thyroxine might result in an overall decrease in cyclic AMP and so accentuate the defective adenyl cyclase activity reported in asthma.9 10 More recently it has been shown in practice that tissue and plasma concentrations of cyclic AMP are higher than normal in hyperthyroidism and are unaffected in hypothyroidism."1 Tissue responsiveness to catecholamines is increased by thyroid hormones and hyperthyroid patients are more sensitive than usual to catecholamines.12 In theory this should benefit patients with coexistent asthma, but in fact asthmatics tend to have worsening of their symptoms and increased side effects from sympathomimetic drugs at the onset of hyperthyroidism.3 The evidence on sympathetic nervous activity in thyroid disease is conflicting. Plasma catecholamine concentrations have been reported as reduced in hyperthyroidism,'3 but other studies have shown no significant changes in plasma adrenaline. Plasma noradrenaline concentrations, however, are normal in hyperthyroidism but raised in hypothyroidism, perhaps in an attempt to compensate for lack of thyroid hormone.14 Dopamine-f-hydroxylase (DBH), an enzyme catalysing the conversion of dopamine to noradrenaline, is decreased in hyperthyroidism but rises to normal with treatment15; and as DBH is derived mainly from sympathetic nerve endings without reuptake it is thought to be an accurate indicator of sympathetic nervous activity. Thyroxine increases the conversion of hydrocortisone to its inactive 11 -ketone metabolites and the rate of steroid reduction in the liver. In hyperthyroidism urinary excretion of conjugated steroid metabolites is increased but free cortisol concentrations in the plasma are reduced.16 The reverse effects are present in hypothyroidism. The onset of hyperthyroidism has certainly been found to increase the steroid requirements for treatment of established asthma.3 So possibly more than one of these mechanisms may be implicated in the effects of thyroid disease on coexistent asthma, but the effects on corticosteroid metabolism seem most likely to be relevant. Though hypothyroidism may be associated with some improvement in asthma, it would be inadvisable for the doctor to try to control asthma in patients with thyroid disease by deliberately producing hypothyroidism. Instead he should aim at restoring the euthyroid state with minimal treatment while controlling the asthma with the appropriate drugs. Feinberg, S M, in Allergy in Practice, p. 90. Chicago, Year Book Medical Publishers, 1944. Kasperlik-Zaluska, A, Gruzlica, 1968, 36, 581. 3 Settipane, G A, Schoenfeld, E, and Hamolsky, M W, Jfournal of Allergy and Clinical Immunology, 1972, 49, 348. I
2
BRITISH MEDICAL JOURNAL
5 NOVEMBER 1977
Bush, R K, Ehrlich, E N, and Reed, C E, Journal of Allergy and Clinical Immunology, 1977, 59, 398. Carlston, J A, Annals of Allergy, 1965, 23, 331. 6 Schwartz, H J, Annals of Allergy, 1966, 24, 234. 7 Satoyoshi, E, et al, Neurology, 1963, 13, 645. 8 Sutherland, E W, and Robison, G A, Pharmacological Reviews, 1966, 18, 145. 9 Logsdon, P J, Middleton, E, and Coffey, R G, Journal of Allergy and Clinical Immunology, 1972, 50, 45. 10 Parker, C W, Huber, M G, and Baumann, M L, Journal of Clinical Investigation, 1973, 52, 1342. "Karlberg, B E, Henriksson, K G, and Andersson, R G G, Journal of Clinical Endocrinology and Metabolism, 1974, 39, 96. 12 Murray, J F, and Kelly, J J, Annals of Internal Medicine, 1959, 51, 309. 13 Stoffer, S S, et al, Journal of Clinical Endocrinology and Metabolism, 1973, 36, 587. 14 Coulombe, P, Dussault, J H, and Walker, P, Metabolism, 1976, 25, 973. 15 Noth, R H, and Spaulding, S W, Journal of Clinical Endocrinology and Metabolism, 1974, 39, 614. 16 Hellman, L, et al, Journal of Clinical Endocrinology and Metabolism, 1961, 21, 1231.
Research priorities Six years after Lord Rothschild first made a casel 2 for the Government's commissioning research on a customercontractor basis the implications of his proposals are still being argued. He recommended a clearer separation of biomedical research (intended to increase knowledge) and health service research (intended to solve practical problems), and criticised the way that the Medical Research Council had financed work that "had and has no customer to commission and approve it." No matter how distinguished or intelligent scientists might be, said Rothschild, they could not be so well qualified to decide the nation's priorities for research expenditure. Returning to this theme in his Rock Carling lecture,3 Sir Andrew Watt Kay set out his considered objections to the Rothschild concept. It might be easy, he said, to obtain more applied science in areas such as defence, but it was naive to believe that the same was true of biology and medicine; and he questioned whether the development of applied research should or could be speeded up by the injection of more money or new management. Medicine differed from industry in one important way, said Sir Andrew. Much new knowledge and new technology tended to increase costs rather than reduce them. The practical import of any new discovery depended on the technological level at which it was made.4 High technology medicine implied understanding of the causation of a disease or at least identification of a specific remedy-antibiotics for bacterial infections, the prevention of rhesus haemolytic disease, the treatment of endocrine disorders with replacement hormones -and was characteristically easy to deliver, simple, and cheap. Here he disagreed with Professor McKeown5 6; Sir Andrew believed that the turn of the century would see a great increase in such specific remedies. Halfway technology medicine, in contrast, included the whole range of treatments given with varying success to minimise disability and suffering from diseases about which there was still insufficient knowledge. Replacement of diseased organs by transplants and prostheses, and operations to improve the blood supply to the heart affected by coronary artery disease, were obvious examples of the enormous costs of such an approach-and there were equally difficult problems of distribution and priority. The third level of technology was the substitute used by the medical profession when there was no means of altering the
