- Email: [email protected]
ASTHMA DEATHS
98 and this
was
increased
to a
maximum of 500 mg. four
times daily.
Despite the stepwise increase and the low maximum dose, only 2 tolerated the maximum dose. One could only take 0-5 g. daily for 14 days. The others were treated for 8-14 weeks. 3 patients were later given levodopa 300 mg. daily with the decarboxylase inhibitorR04-4602’ 75 mg. daily, for 6 weeks. None of the patients improved during treatment with levodopa alone or with the two drugs. The frequency, duration, and severity of the migraine attacks were unaltered. The side-effects were more pronounced than in the treatment of Parkinson’s syndrome, but of the usual type. The results indicate that levodopa, in doses we used, has no effect on migraine. We are not encouraged to perform a larger double-blind trial. Department of Neurology, H. J. HANSEN Kommunehospitalet Århus, E. DUPONT. 8000, Århus C., Denmark.
ASTHMA DEATHS 1-4
noted in SiR,—The increased asthma mortality was thought to be caused by the overdosage of isoprenaline from metered aerosol bottles. Many people felt that isoprenaline used in excess might cause fatal cardiotoxicity;others accused ’Freon’, the fluorocarbon substance used as aerosoliser, as being possibly toxic. In contrast, I pointed out that isoprenaline (and other catecholamines) are well known to cause tolerance when given repeatedly in quick succession (as had happened with asthma patients who died in an attack). My view was supported by experiments and clinical experience.5,6 Now Connolly et al.7 have confirmed the development 1966-67
of tolerance after isoprenaline and after salbutamol in animals and man. They could not find any evidence of cardiotoxicity at the incriminated doses. Freon has been also shown to be non-toxic.s It can therefore be regarded as almost certain that the inhalation of isoprenaline or similar aerosols at intervals of 30, 60, or even 120 minutes On the contrary, over some days will not be cardiotoxic. it will lead to tolerance-that is, to an absence of their normal bronchodilator effect. This is in reality what one notices in practice with such patients, if they start inhaling too often: they complain of lack of relief. If they have no other protective medication, they may easily die if their asthma gets worse-for instance, from an intercurrent infection or an increase of their environmental allergens. As the reasons for such fatalities are now established, the first consequence is clear: the practitioner should energetically prevent his asthmatic patients from using their metered bottles more often than once in 3 hours, whatever the individual dose (the dose is the number of puffs at any one time), and the appropriate instructions for use should be clearly stated. If the patient seems unable to follow this restriction, he should be given additional effective medication-usually Another consequence is that with all corticosteroids. catecholamines frequent medication should be avoided. Even three doses a day may lead to tolerance, particularly with the oral or sublingual substances (isoprenaline, orciorenaline salbutamol. terbutaline, ephedrine). Department of Clinical Immunology and Asthma Poliklinik, Rudolf Virchow Krankenhaus, Berlin 65.
H. HERXHEIMER.
Lancet, 1968, i, 412. 1969, ii, 305. 3. Herxheimer, H. ibid. 1968, ii, 216. 4. Herxheimer, H. ibid. 1969, ii, 642. 5. Herxheimer, H. Br. med. J. 1946, i, 350. 6. Herxheimer, H. Management of Bronchial Asthma; p. 43. London, 1.
2. ibid.
1952. 7. Connolly, M., Davies, D. S., Dollery, C. T., George, C. F. Br. J. Pharmacol. 1971, 43, 389. 8. Paterson, J. W., Sudlow, M. F., Walker, R. S. Lancet, 1971, ii, 565.
S.M.O.N. to certain analogies that of subacute relationship appear myelo-optic neuropathy (S.M.O.N.) to clioquinol and pink disease to calomel-containing teething powders. In an annotation, in 1953, occasioned by the inquest on a child dying with pink disease due to " innocent overdosage of teething powder ", you pointed out that calomel-containing powders were still being sold without regard for the growing awareness over the year past that mercury was in some way responsible. Reports of this association were then coming in from America, Australia, and South Africa, as well as from Britain. As you justly mentioned, many peadiatricians were unconvinced that mercury was a common cause of pink disease in this country ". You even cited authors who found less pink disease where the taking of teething powders was frequent and vice versa. Such views spring from many causes, but the fact remains
SIR,-May I draw attention to
exist between the
"
that when the manufacturers announced a week later at another inquest that their teething powders no longer contained calomel, the numbers of cases of pink disease declined steadily from that time until the disease disappeared. The real relationship between the two will probably never be known, but the point is that infants were being poisoned by giving a drug unnecessarily for which adequate harmless substitutes existed. The same might well be said for clioquinol, which has not been proven to have any beneficial effect upon chronic diarrhtsat diseases,2 and for which other more effective agents exist that do not damage the nervous svstem. M.R.C. Research Group in
Applied Neurobiology, Institute of Neurology, 8/11 Queen Square,
J. B. CAVANAGH.
London W.C.1.
EMPLOYMENT MEDICAL ADVISORY SERVICE BILL
SIR,-It was pointed out in the earlier debate on this Bill, before it lapsed with the departure of the Labour Government, that it confused two separate issues: an occupational health service, and the care of young people in industry. It had been a matter for reasonable hope that the present Government would have given a little consideration to separating the two. The new Bill is a lamentable exhibition of muddled thinking. So far as young people are concerned the little they have, on the medical side, is to be taken away because of gross Departmental and medical neglect to use opportunities. These opportunities are to be destroyed. All the Department of Employment has ever done is to reiterate in monotonous manner (I quote from a Departmental letter dated Dec. 10, 1971 3) We are confident that the introduction of the new Service, together with future proposals for the development of the Youth Employment Service and in particular for it to work in collaboration with the new Service, will go a long way towards achieving the improvement that we are anxious to make in the medical supervision, where needed, of young persons entering employment ". Where needed " (my italics). What is needed and what "
"
is need ? The following are or even considered:
some
of the
questions
(1) Who other than those who might Register will be seen by the doctor ?
be
1. Lancet, 1953, ii, 1247. 2. Marsden, P. D., Knight, R. ibid. 1971, i, 854. 3. See Lancet, 1971, ii, 1300; ibid. p. 1432.
never
on
answered
the
Disabled
was
increased
to a
maximum of 500 mg. four
times daily.
Despite the stepwise increase and the low maximum dose, only 2 tolerated the maximum dose. One could only take 0-5 g. daily for 14 days. The others were treated for 8-14 weeks. 3 patients were later given levodopa 300 mg. daily with the decarboxylase inhibitorR04-4602’ 75 mg. daily, for 6 weeks. None of the patients improved during treatment with levodopa alone or with the two drugs. The frequency, duration, and severity of the migraine attacks were unaltered. The side-effects were more pronounced than in the treatment of Parkinson’s syndrome, but of the usual type. The results indicate that levodopa, in doses we used, has no effect on migraine. We are not encouraged to perform a larger double-blind trial. Department of Neurology, H. J. HANSEN Kommunehospitalet Århus, E. DUPONT. 8000, Århus C., Denmark.
ASTHMA DEATHS 1-4
noted in SiR,—The increased asthma mortality was thought to be caused by the overdosage of isoprenaline from metered aerosol bottles. Many people felt that isoprenaline used in excess might cause fatal cardiotoxicity;others accused ’Freon’, the fluorocarbon substance used as aerosoliser, as being possibly toxic. In contrast, I pointed out that isoprenaline (and other catecholamines) are well known to cause tolerance when given repeatedly in quick succession (as had happened with asthma patients who died in an attack). My view was supported by experiments and clinical experience.5,6 Now Connolly et al.7 have confirmed the development 1966-67
of tolerance after isoprenaline and after salbutamol in animals and man. They could not find any evidence of cardiotoxicity at the incriminated doses. Freon has been also shown to be non-toxic.s It can therefore be regarded as almost certain that the inhalation of isoprenaline or similar aerosols at intervals of 30, 60, or even 120 minutes On the contrary, over some days will not be cardiotoxic. it will lead to tolerance-that is, to an absence of their normal bronchodilator effect. This is in reality what one notices in practice with such patients, if they start inhaling too often: they complain of lack of relief. If they have no other protective medication, they may easily die if their asthma gets worse-for instance, from an intercurrent infection or an increase of their environmental allergens. As the reasons for such fatalities are now established, the first consequence is clear: the practitioner should energetically prevent his asthmatic patients from using their metered bottles more often than once in 3 hours, whatever the individual dose (the dose is the number of puffs at any one time), and the appropriate instructions for use should be clearly stated. If the patient seems unable to follow this restriction, he should be given additional effective medication-usually Another consequence is that with all corticosteroids. catecholamines frequent medication should be avoided. Even three doses a day may lead to tolerance, particularly with the oral or sublingual substances (isoprenaline, orciorenaline salbutamol. terbutaline, ephedrine). Department of Clinical Immunology and Asthma Poliklinik, Rudolf Virchow Krankenhaus, Berlin 65.
H. HERXHEIMER.
Lancet, 1968, i, 412. 1969, ii, 305. 3. Herxheimer, H. ibid. 1968, ii, 216. 4. Herxheimer, H. ibid. 1969, ii, 642. 5. Herxheimer, H. Br. med. J. 1946, i, 350. 6. Herxheimer, H. Management of Bronchial Asthma; p. 43. London, 1.
2. ibid.
1952. 7. Connolly, M., Davies, D. S., Dollery, C. T., George, C. F. Br. J. Pharmacol. 1971, 43, 389. 8. Paterson, J. W., Sudlow, M. F., Walker, R. S. Lancet, 1971, ii, 565.
S.M.O.N. to certain analogies that of subacute relationship appear myelo-optic neuropathy (S.M.O.N.) to clioquinol and pink disease to calomel-containing teething powders. In an annotation, in 1953, occasioned by the inquest on a child dying with pink disease due to " innocent overdosage of teething powder ", you pointed out that calomel-containing powders were still being sold without regard for the growing awareness over the year past that mercury was in some way responsible. Reports of this association were then coming in from America, Australia, and South Africa, as well as from Britain. As you justly mentioned, many peadiatricians were unconvinced that mercury was a common cause of pink disease in this country ". You even cited authors who found less pink disease where the taking of teething powders was frequent and vice versa. Such views spring from many causes, but the fact remains
SIR,-May I draw attention to
exist between the
"
that when the manufacturers announced a week later at another inquest that their teething powders no longer contained calomel, the numbers of cases of pink disease declined steadily from that time until the disease disappeared. The real relationship between the two will probably never be known, but the point is that infants were being poisoned by giving a drug unnecessarily for which adequate harmless substitutes existed. The same might well be said for clioquinol, which has not been proven to have any beneficial effect upon chronic diarrhtsat diseases,2 and for which other more effective agents exist that do not damage the nervous svstem. M.R.C. Research Group in
Applied Neurobiology, Institute of Neurology, 8/11 Queen Square,
J. B. CAVANAGH.
London W.C.1.
EMPLOYMENT MEDICAL ADVISORY SERVICE BILL
SIR,-It was pointed out in the earlier debate on this Bill, before it lapsed with the departure of the Labour Government, that it confused two separate issues: an occupational health service, and the care of young people in industry. It had been a matter for reasonable hope that the present Government would have given a little consideration to separating the two. The new Bill is a lamentable exhibition of muddled thinking. So far as young people are concerned the little they have, on the medical side, is to be taken away because of gross Departmental and medical neglect to use opportunities. These opportunities are to be destroyed. All the Department of Employment has ever done is to reiterate in monotonous manner (I quote from a Departmental letter dated Dec. 10, 1971 3) We are confident that the introduction of the new Service, together with future proposals for the development of the Youth Employment Service and in particular for it to work in collaboration with the new Service, will go a long way towards achieving the improvement that we are anxious to make in the medical supervision, where needed, of young persons entering employment ". Where needed " (my italics). What is needed and what "
"
is need ? The following are or even considered:
some
of the
questions
(1) Who other than those who might Register will be seen by the doctor ?
be
1. Lancet, 1953, ii, 1247. 2. Marsden, P. D., Knight, R. ibid. 1971, i, 854. 3. See Lancet, 1971, ii, 1300; ibid. p. 1432.
never
on
answered
the
Disabled