1296 for teething, a definite hepatitis was associated with the acidosis. We would agree with Mitchell that the hazards of giving aspirin to infants should be better publicised, and perhaps its general availability (e.g., in supermarkets) should be curtailed. In any infant presenting with hepatitis or acidosis salicylate intoxication should be remembered and excluded. D. T. D. BULUGAHAPITIYA
given salicylate
Rotherham District General Rotherham S60 2UD
Hospital,
B. HEBRON
P. R. BECK
PRENATAL DIAGNOSIS OF TAY-SACHS DISEASE
SIR,-In your May 5 issue (p. 972) Dr Perry and colleagues discuss the use of blood obtained at fetoscopy for the prenatal detection of Tay-Sachs disease. This proposal is prompted by the desire to establish a diagnosis without warning for three or four weeks until amniotic-fluid cells are cultured. In Tay-Sachs disease, however, it is generally possible to obtain a safe result after amniotic puncture by examining amniotic fluid or fresh amniotic cells. We use fresh amniotic cells, collected by centrifugation of 5 ml amniotic fluid. They are lysed by repeated freezing and thawing, and taken up in 50 ul water. The lysate is submitted to electrophoresis on cellulose acetate’ and stained with the fluorogenic substrate 4-methyl-umbelliforyl-&bgr;-glucosaminide. This procedure has been used in three cases of pregnancy at risk for Tay-Sachs disease. In the three cases, the two bands of hexosaminidases A and B were clearly visible, excluding a deficiency in hexosaminidase A.2 Our routine practice is to culture cells as well; and the procedure was repeated on these cultured cells with the same result. Amniotic supernatant fluid can also be used but the results are much less clear-cut. The figure shows the results in
typical case. As Perry et al. point out fetoscopy is a much more difficult and invasive technique than amniocentesis. We do not think that in Tay-Sachs disease it should be recommended. We propose that a first diagnosis be made on fresh cells; abortion
a
should not be advised until confirmation been obtained. Institut de Pathologie Moléculaire, 75674 Cedex 14 Paris, France.
on
EDITORIAL INDEPENDENCE OF PRESCRIBERS’
JOURNAL SIR,—I surprised by the letter from Dr Hamer and Professor Turner (May 26, p. 1150) concerning the rejection by the Editorial Board of Prescribers’ Journal of an article commissioned from Dr Hamer. As Dr Hamer knows, the reason to which he has chosen to give publicity formed only one of the bases on which the Board decided to reject his article. I have been associated with Prescribers’ Journal since 1972 and can assure Dr Hamer and Professor Turner that there is no Editorial Board policy about rejection of articles on any doctrinaire basis, as they suggest. In my view the function of the journal is not to point the way to new trends in therapeutics, as do editorials in weekly journals, but to function on a more practical basis by guiding practitioners how best to use available and accepted drugs. If a drug does not have a product licence for an indication-i.e., the company concerned does not market it for that purpose-then for a journal such as ours to advocate its use would not be of value to our readers. This is the case with respect to vasodilators in heart-failure. Their suggestion of governmental bureaucratic censorship is equally misplaced. While the journal is financed by the Department of Health and Social Security and the editorial staff are Departmental employees, the editor is not a full member of the Committee of Management which is an independent body composed predominantly of clinicians. Further, the editor is not the final arbiter of what shall be published. The onus of making such decisions rests with the Committee of Management, and the editor and his deputy carry the responsibility of implementing its decisions. While I welcome the interest that Dr Hamer and Professor Turner have shown in the journal, I am taken aback that they have chosen a public vehicle to discuss a matter which could have been better settled more privately. was
Department of Pharmacology, University of Liverpool, Liverpool L69 3BX
1. Poenaru, L., Dreyfus, J. C. Clin. chim. Acta, 1973, 43, 439. 2. Poenaru, L., Dreyfus, J. C. in Prenatal Diagnosis (edited and others); p. 284. Stuttgart, 1979.
by J.
D. Murken
Chairman, Committee of Management of Prescribers’
cultured cells has
J. C. DREYFUS L. POENARU
ALASDAIR M. BRECKENRIDGE, Journal
CONSULTANT CONTRACT
SIR,—Now that the Review Body’s report has been published it will not take long, despite some misleading Press reports, for consultants to learn the full extent of the disaster they now face. There is no crock of gold. Although our negotiators stomped the country virtually promising that the present whole-time salary would be equated with payment for the 10 basic sessions of the new contract it has been equated with 13, and under the new arrangements the value that has been accorded to those who are on call 24 hours a day, 7 days a week is just 1 session. All this is bad, but what is far worse is the fact that the security promised to those who wish to retain their present contract has proved to be nothing but an illusion. The Health
Departments regard that promise as contractual and not financial, and the Review Body has agreed with them. Those of us who opt to retain our present contract will have incomes protected to some extent, but not in the future. If we do not move to the new contract financial pressures will be exerted to make us change our minds. Furthermore, the whole basis of the existing contract has been undermined by the introduction of emergency recall fees. The money to pay these will be found by reducing the level of our basic pay. Those who do them will be paid at the expense of those who do not, and as each year passes and the number of recalls increases the basic consultant salary will be progressively lowered to pay for them. The income from these fees is not pensionable so that even consultants who receive them will lose in the long run; those who do not, about half the consultants in the country, will lose twice. As the full horror of it all is revealed I expect our negotiators
our
N-glucosaminidase electrophoresis. l=non-cultured amniouc cells (propositus.) 2=cultured amniotic cells (propositus.) 3=control cultured amniotic cells.
1297 blame everyone but themselves-the Health Departments who simply outwitted them and the Review Body which has done precisely what it said it would do. A year ago I predicted what would happen and that, as a consequence, the Review Body system itself would be placed in danger.’ As your readers may know I have never been a supporter of the D.H.S.S. or the Review Body but in my view the real fault lies with our negotiators who chose to mislead the profession and repeatedly and deliberately ignored the warnings of the dangers they themselves were creating for us all. I will take no action whatsoever to save their faces or their necks: the profession’s negotiators should admit that the mistake was theirs and resign. to
Guy’s Hospital,
N. A. SIMMONS
London SE1
*** The British Medical Association’s reactions discussed by Body’s report dent on p. 1304.-ED.L. are
our
to
Parliamentary
the Review correspon-
PSYCHIATRIC DISORDERS FOLLOWING INFANTILE SPASMS
SIR,—Infantile spasms (West’s syndrome)2may present with comparatively mild symptoms usually in the first year of life. The attacks, often called "salaam" or "jack-knife" are brief, each lasting about a second and practically always occurring at intervals of seconds over a period of several minutes. When they appear in an otherwise healthy child these spasms may be dismissed as "colic" or "wind" by parents and sometimes by inexperienced doctors, until mental and motor regression becomes obvious, revealing the true gravity of the illness 3-y We would like to report some preliminary findings of a long-term follow-up of patients referred to the Department of Clinical Neurophysiology, Hospital for Sick Children, with the infantile-spasm syndrome, from July, 1960, to December, 1963. The first 100 patients traced by 1978 form the basis of this study; follow-up was 15-18 years, and the patients were classified as follows: Group A-24 were found to have died. Group B-31 patients in late adolescence were in permanent care in hospitals for the mentally subnormal. Group C-17 patients in essentially the same clinical state as in group B but being cared for at home by their parents. Group D-20 patients had made a reasonably good recovery though with various residual disabilities. Group E-Only 8 patients had made a good recovery. The question of early and appropriate treatment cannot be discussed in a brief note. No necropsies had been done on any of the 10 children who had died in institutions for the mentally subnormal while only 3 necropsies had been done in the remaining 14 cases of group A. The 48 patients in groups B and C were severely disabled, many bed-ridden or chair-bound, unable to speak, incontinent, incapable of any self care, and having to be fed. Some, who had originally recovered enough to be able to walk, were confined to bed or wheelchair because of deformities and contractures developed over the years despite surgery, splints, and other appliances. Some appeared blind and/or deaf but speech was invariably affected even though in 18 patients some degree of verbal comprehension and ability to communicate by gesture was preserved. In the more severely affected, however,
1. Simmons, N. A. On Call, June 8, 1978, p.7. 2. West, W. J. Lancet, 1841, i, 724. 3. Gibbs, E. L., Fleming, M. M., Gibbs, F. A. Pediatrics, 1954, 33, 66. 4.Sorel, L., Dusaucy-Bauloye, A. Acta neurol, psychiat. belg. 1958, 58, 130. 5. Jeavons, P. M., Bower, B. D. Clin. devel. Med. 1964, no. 15. 6. della Rovere, M., Hoare, R. D., Pampiglione, G. Devel. Med Child Neurol.
1964, 6, 149. E., Pampiglione, G. ibid. 1964, 6, 149. 8. Pampiglione, G., Moynahan, E. J., J. Neurol. Neurosurg. Psychiat. 1976, 39, 666. 9. Jeavons, P. M., Bower, B. D., Dimitrakoudi, M. Epilepsia, 1973, 14, 153.
7. Friedman, I.
there was little, if any, contact with surroundings or recognition of parents or nurses. It was difficult in these severely handicapped children to differentiate the psychiatric problems, which became more prominent with increasing age, from the persistent motor and mental defects. The 20 patients in group D had recovered from the spasms and other seizures with gradual resumption of developmental progress, even though this was delayed. The residual neurological handicap was limited to mild athetosis, clumsiness or some degree of spasticity. All were educable, attaining at least schooling for educationally subnormal and 10 reached the lower streams of normal schools. All were able to speak though many had slight stammering, echolalia, or word substitution. However, in group D psychiatric disorders were a distinct feature with greater or lesser hyperactivity, temper tantrums, aggressive/destructive behaviour, pica, bouts of head-banging or rocking, gaze avoidance, and hand regard, generally considered characteristic of autistic behaviour. Over the years, most patients in group D had been treated for emotional problems in child-guidance clinics. It seems probable that these psychiatric manifestations were caused by the same braindisease process which, at an earlier age, had appeared in the form of the "infantile spasms syndrome" with severe E.E.G. abnormalities. The general neurological features and the mental handicap in the present series were on the whole similar to those of previous studies (see Lacy and Penry’s review’O) and therefore not entirely unexpected. We had not, however, anticipated the large number of psychiatric sequelae in the less badly affected survivors, and we do not think that selective referral to this hospital could account for these findings. This aspect has received little attention in the literature. Our study suggests that the infantile-spasms syndrome is still insufficiently understood in respect of aetiology, epidemiology, evolution (including psychiatric manifestations), and biochemical and histopathological features. A prospective research programme should be considered to assess the incidence of the condition in Britain and its implications, to establish a national register, to provide facilities for early or even presymptomatic detection, and to rationalise treatment in the various phases of evolution. We thank our medical colleagues who answered our inquiries, convaluable information, and the medical records officers in many hospitals, especially Miss P. Corns.
tributing
Department of Clinical Neurophysiology, Hospital for Sick Children,
E. M. THORNTON G. PAMPIGLIONE
London WC1
ORAL PROSTAGLANDIN E2 IN PULMONARY ATRESIA
SIR,-Short-term intravenous prostaglandin E1
or
E2
is used in some centres to maintain the patency of the ductus arteriosus in neonates who have no other source of pulmonary blood-flow. It is generally used for 24-48 h while cardiac surgery is arranged. The increased pulmonary blood-flow results in improved tissue oxygenation, permitting correction of metabolic acidosis and making surgery less risky.’-’ The longest reported infusion of p.G.Ej has been 29 days.8 Long-term p.G.E may be beneficial in certain cases but there are practical limitations to intra-aortic or intravenous in-
(P.G.E1
10.
or
P.G.E2)
Lacy, J. R., Penry, J. K. Infantile Spasms, New York, 1976. Starling, M, B., Neutz, J. M. Lancet, 1975, i, 140.
1. Elliot, R., R, B.,
2. Christen, N C, Fabricus, J ibid 1975, ii, 406. 3. Olley, P. M. Coceani, F., Bodach, E Circulation, 1976, 53, 728. M. Pediatrics, 1977, 59, 325. 4. Heymann, M. A., Rudolph, A. 5. Moulaert, A., Senders, R., van Ertbruggen, I , Huysmans, H., Harinck, E.
Eur. J. Cardiol. 1977, 5, 321. J. M., Starling, M B., Elliot, 1977, 55, 238
6. Neutz 7.
8.
Lewis,. A. L., Takahashi, M.,
R B.,
Barrat-Boyes, B. G. Circulation,
Lurie, P. R. J. Pediat. 1978, 93, 481.
Lewis,. A. L., Lurie, P.R. Pediatrics,
1978, 61, 524.
given salicylate
Rotherham District General Rotherham S60 2UD
Hospital,
B. HEBRON
P. R. BECK
PRENATAL DIAGNOSIS OF TAY-SACHS DISEASE
SIR,-In your May 5 issue (p. 972) Dr Perry and colleagues discuss the use of blood obtained at fetoscopy for the prenatal detection of Tay-Sachs disease. This proposal is prompted by the desire to establish a diagnosis without warning for three or four weeks until amniotic-fluid cells are cultured. In Tay-Sachs disease, however, it is generally possible to obtain a safe result after amniotic puncture by examining amniotic fluid or fresh amniotic cells. We use fresh amniotic cells, collected by centrifugation of 5 ml amniotic fluid. They are lysed by repeated freezing and thawing, and taken up in 50 ul water. The lysate is submitted to electrophoresis on cellulose acetate’ and stained with the fluorogenic substrate 4-methyl-umbelliforyl-&bgr;-glucosaminide. This procedure has been used in three cases of pregnancy at risk for Tay-Sachs disease. In the three cases, the two bands of hexosaminidases A and B were clearly visible, excluding a deficiency in hexosaminidase A.2 Our routine practice is to culture cells as well; and the procedure was repeated on these cultured cells with the same result. Amniotic supernatant fluid can also be used but the results are much less clear-cut. The figure shows the results in
typical case. As Perry et al. point out fetoscopy is a much more difficult and invasive technique than amniocentesis. We do not think that in Tay-Sachs disease it should be recommended. We propose that a first diagnosis be made on fresh cells; abortion
a
should not be advised until confirmation been obtained. Institut de Pathologie Moléculaire, 75674 Cedex 14 Paris, France.
on
EDITORIAL INDEPENDENCE OF PRESCRIBERS’
JOURNAL SIR,—I surprised by the letter from Dr Hamer and Professor Turner (May 26, p. 1150) concerning the rejection by the Editorial Board of Prescribers’ Journal of an article commissioned from Dr Hamer. As Dr Hamer knows, the reason to which he has chosen to give publicity formed only one of the bases on which the Board decided to reject his article. I have been associated with Prescribers’ Journal since 1972 and can assure Dr Hamer and Professor Turner that there is no Editorial Board policy about rejection of articles on any doctrinaire basis, as they suggest. In my view the function of the journal is not to point the way to new trends in therapeutics, as do editorials in weekly journals, but to function on a more practical basis by guiding practitioners how best to use available and accepted drugs. If a drug does not have a product licence for an indication-i.e., the company concerned does not market it for that purpose-then for a journal such as ours to advocate its use would not be of value to our readers. This is the case with respect to vasodilators in heart-failure. Their suggestion of governmental bureaucratic censorship is equally misplaced. While the journal is financed by the Department of Health and Social Security and the editorial staff are Departmental employees, the editor is not a full member of the Committee of Management which is an independent body composed predominantly of clinicians. Further, the editor is not the final arbiter of what shall be published. The onus of making such decisions rests with the Committee of Management, and the editor and his deputy carry the responsibility of implementing its decisions. While I welcome the interest that Dr Hamer and Professor Turner have shown in the journal, I am taken aback that they have chosen a public vehicle to discuss a matter which could have been better settled more privately. was
Department of Pharmacology, University of Liverpool, Liverpool L69 3BX
1. Poenaru, L., Dreyfus, J. C. Clin. chim. Acta, 1973, 43, 439. 2. Poenaru, L., Dreyfus, J. C. in Prenatal Diagnosis (edited and others); p. 284. Stuttgart, 1979.
by J.
D. Murken
Chairman, Committee of Management of Prescribers’
cultured cells has
J. C. DREYFUS L. POENARU
ALASDAIR M. BRECKENRIDGE, Journal
CONSULTANT CONTRACT
SIR,—Now that the Review Body’s report has been published it will not take long, despite some misleading Press reports, for consultants to learn the full extent of the disaster they now face. There is no crock of gold. Although our negotiators stomped the country virtually promising that the present whole-time salary would be equated with payment for the 10 basic sessions of the new contract it has been equated with 13, and under the new arrangements the value that has been accorded to those who are on call 24 hours a day, 7 days a week is just 1 session. All this is bad, but what is far worse is the fact that the security promised to those who wish to retain their present contract has proved to be nothing but an illusion. The Health
Departments regard that promise as contractual and not financial, and the Review Body has agreed with them. Those of us who opt to retain our present contract will have incomes protected to some extent, but not in the future. If we do not move to the new contract financial pressures will be exerted to make us change our minds. Furthermore, the whole basis of the existing contract has been undermined by the introduction of emergency recall fees. The money to pay these will be found by reducing the level of our basic pay. Those who do them will be paid at the expense of those who do not, and as each year passes and the number of recalls increases the basic consultant salary will be progressively lowered to pay for them. The income from these fees is not pensionable so that even consultants who receive them will lose in the long run; those who do not, about half the consultants in the country, will lose twice. As the full horror of it all is revealed I expect our negotiators
our
N-glucosaminidase electrophoresis. l=non-cultured amniouc cells (propositus.) 2=cultured amniotic cells (propositus.) 3=control cultured amniotic cells.
1297 blame everyone but themselves-the Health Departments who simply outwitted them and the Review Body which has done precisely what it said it would do. A year ago I predicted what would happen and that, as a consequence, the Review Body system itself would be placed in danger.’ As your readers may know I have never been a supporter of the D.H.S.S. or the Review Body but in my view the real fault lies with our negotiators who chose to mislead the profession and repeatedly and deliberately ignored the warnings of the dangers they themselves were creating for us all. I will take no action whatsoever to save their faces or their necks: the profession’s negotiators should admit that the mistake was theirs and resign. to
Guy’s Hospital,
N. A. SIMMONS
London SE1
*** The British Medical Association’s reactions discussed by Body’s report dent on p. 1304.-ED.L. are
our
to
Parliamentary
the Review correspon-
PSYCHIATRIC DISORDERS FOLLOWING INFANTILE SPASMS
SIR,—Infantile spasms (West’s syndrome)2may present with comparatively mild symptoms usually in the first year of life. The attacks, often called "salaam" or "jack-knife" are brief, each lasting about a second and practically always occurring at intervals of seconds over a period of several minutes. When they appear in an otherwise healthy child these spasms may be dismissed as "colic" or "wind" by parents and sometimes by inexperienced doctors, until mental and motor regression becomes obvious, revealing the true gravity of the illness 3-y We would like to report some preliminary findings of a long-term follow-up of patients referred to the Department of Clinical Neurophysiology, Hospital for Sick Children, with the infantile-spasm syndrome, from July, 1960, to December, 1963. The first 100 patients traced by 1978 form the basis of this study; follow-up was 15-18 years, and the patients were classified as follows: Group A-24 were found to have died. Group B-31 patients in late adolescence were in permanent care in hospitals for the mentally subnormal. Group C-17 patients in essentially the same clinical state as in group B but being cared for at home by their parents. Group D-20 patients had made a reasonably good recovery though with various residual disabilities. Group E-Only 8 patients had made a good recovery. The question of early and appropriate treatment cannot be discussed in a brief note. No necropsies had been done on any of the 10 children who had died in institutions for the mentally subnormal while only 3 necropsies had been done in the remaining 14 cases of group A. The 48 patients in groups B and C were severely disabled, many bed-ridden or chair-bound, unable to speak, incontinent, incapable of any self care, and having to be fed. Some, who had originally recovered enough to be able to walk, were confined to bed or wheelchair because of deformities and contractures developed over the years despite surgery, splints, and other appliances. Some appeared blind and/or deaf but speech was invariably affected even though in 18 patients some degree of verbal comprehension and ability to communicate by gesture was preserved. In the more severely affected, however,
1. Simmons, N. A. On Call, June 8, 1978, p.7. 2. West, W. J. Lancet, 1841, i, 724. 3. Gibbs, E. L., Fleming, M. M., Gibbs, F. A. Pediatrics, 1954, 33, 66. 4.Sorel, L., Dusaucy-Bauloye, A. Acta neurol, psychiat. belg. 1958, 58, 130. 5. Jeavons, P. M., Bower, B. D. Clin. devel. Med. 1964, no. 15. 6. della Rovere, M., Hoare, R. D., Pampiglione, G. Devel. Med Child Neurol.
1964, 6, 149. E., Pampiglione, G. ibid. 1964, 6, 149. 8. Pampiglione, G., Moynahan, E. J., J. Neurol. Neurosurg. Psychiat. 1976, 39, 666. 9. Jeavons, P. M., Bower, B. D., Dimitrakoudi, M. Epilepsia, 1973, 14, 153.
7. Friedman, I.
there was little, if any, contact with surroundings or recognition of parents or nurses. It was difficult in these severely handicapped children to differentiate the psychiatric problems, which became more prominent with increasing age, from the persistent motor and mental defects. The 20 patients in group D had recovered from the spasms and other seizures with gradual resumption of developmental progress, even though this was delayed. The residual neurological handicap was limited to mild athetosis, clumsiness or some degree of spasticity. All were educable, attaining at least schooling for educationally subnormal and 10 reached the lower streams of normal schools. All were able to speak though many had slight stammering, echolalia, or word substitution. However, in group D psychiatric disorders were a distinct feature with greater or lesser hyperactivity, temper tantrums, aggressive/destructive behaviour, pica, bouts of head-banging or rocking, gaze avoidance, and hand regard, generally considered characteristic of autistic behaviour. Over the years, most patients in group D had been treated for emotional problems in child-guidance clinics. It seems probable that these psychiatric manifestations were caused by the same braindisease process which, at an earlier age, had appeared in the form of the "infantile spasms syndrome" with severe E.E.G. abnormalities. The general neurological features and the mental handicap in the present series were on the whole similar to those of previous studies (see Lacy and Penry’s review’O) and therefore not entirely unexpected. We had not, however, anticipated the large number of psychiatric sequelae in the less badly affected survivors, and we do not think that selective referral to this hospital could account for these findings. This aspect has received little attention in the literature. Our study suggests that the infantile-spasms syndrome is still insufficiently understood in respect of aetiology, epidemiology, evolution (including psychiatric manifestations), and biochemical and histopathological features. A prospective research programme should be considered to assess the incidence of the condition in Britain and its implications, to establish a national register, to provide facilities for early or even presymptomatic detection, and to rationalise treatment in the various phases of evolution. We thank our medical colleagues who answered our inquiries, convaluable information, and the medical records officers in many hospitals, especially Miss P. Corns.
tributing
Department of Clinical Neurophysiology, Hospital for Sick Children,
E. M. THORNTON G. PAMPIGLIONE
London WC1
ORAL PROSTAGLANDIN E2 IN PULMONARY ATRESIA
SIR,-Short-term intravenous prostaglandin E1
or
E2
is used in some centres to maintain the patency of the ductus arteriosus in neonates who have no other source of pulmonary blood-flow. It is generally used for 24-48 h while cardiac surgery is arranged. The increased pulmonary blood-flow results in improved tissue oxygenation, permitting correction of metabolic acidosis and making surgery less risky.’-’ The longest reported infusion of p.G.Ej has been 29 days.8 Long-term p.G.E may be beneficial in certain cases but there are practical limitations to intra-aortic or intravenous in-
(P.G.E1
10.
or
P.G.E2)
Lacy, J. R., Penry, J. K. Infantile Spasms, New York, 1976. Starling, M, B., Neutz, J. M. Lancet, 1975, i, 140.
1. Elliot, R., R, B.,
2. Christen, N C, Fabricus, J ibid 1975, ii, 406. 3. Olley, P. M. Coceani, F., Bodach, E Circulation, 1976, 53, 728. M. Pediatrics, 1977, 59, 325. 4. Heymann, M. A., Rudolph, A. 5. Moulaert, A., Senders, R., van Ertbruggen, I , Huysmans, H., Harinck, E.
Eur. J. Cardiol. 1977, 5, 321. J. M., Starling, M B., Elliot, 1977, 55, 238
6. Neutz 7.
8.
Lewis,. A. L., Takahashi, M.,
R B.,
Barrat-Boyes, B. G. Circulation,
Lurie, P. R. J. Pediat. 1978, 93, 481.
Lewis,. A. L., Lurie, P.R. Pediatrics,
1978, 61, 524.
