1200 metabolism in all of these diseases suggests that only limited benefit will ensue from levodopa therapy in patients afflicted with " abiotrophic dementias ".
impaired
G.A.B.A.
Miriam Marks Department of
Neurochemistry, Institute of Neurology, National Hospital, Queen Square,
DAVID M. BOWEN ALAN N. DAVISON.
London WC1N 3BG.
DOWN SYNDROME IN INDIA
SIR,-In a worldwide study of congenital malformations organised by the World Health Organisation no cases of Down syndrome were reported from India among 59,689 births in Bombay and Calcutta. There were no cases in 4141 births to Indian mothers in Kuala Lumpur, and only
ADRENAL SUPPRESSION BY CLOBETASOL
PROPIONATE SIR,—Until recently we have assumed that normal skin
constitutes an effective barrier to the absorption of corticosteroids. Application of potent steroids to diseased skin may produce transient suppression of pituitary-adrenal function, but the efficiency of the barrier increases with clinical improvement. Adrenal function recovers despite continuing steroid application. The increasingly effective combination of potent steroids and scientifically optimal bases threatens this physiological safety valve. We found that two of our topical corticosteroid preparations caused important adrenal suppression when applied to normal
1 affected child
was born to 3119 Indian mothers in In Singapore. all, there was only 1 child with Down to born 66,000 Indian mothers. These observasyndrome
FREQUENCY
OF
DOWN
SYNDROME
IN
SURVEYS
OF
NEWBORNS
IN INDIA
generated an impression that the frequency of Down syndrome in India is extremely low. This, however, is contrary to clinical experience of most paediatricians in India. Over 125 patients with Down syndrome have been evaluated in the genetics clinic in our hospital over a 4-year period. In the neonatal unit of our hospital, 4 infants with Down syndrome (confirmed by cytogenetic studies) have been detected among 3236 live births, giving a frequency of 1 per 809 live births (1-24 per 1000). Information from other Indian surveys of consecutive newborns gives a mean frequency of 1 per 1215 births (0-82 per 1000), with a range from 0-26 to 1-6 per 1000 births (see table). Excluding the data from Madras, which appears to have a low incidence, the mean frequency is 1-19 per 1000 births from among 35,325 births (range 0-73 to 1-6). The combined results of 9 surveys in Europe, North America, and Australiagave an average of 1 per 663 births (1-51 per 1000 births), with a range of 1-15 to 1-9 per 1000 births.
. &mid ot;
tions
5 chromosomal surveys of newborns in the U.K. and North America yielded a mean of 1-0 per 1000 births, with a range of 0 among 2081 births in London, Ontario, to 1-5 per 1000 births in Edinburgh. The frequency of Down syndrome, therefore, does not appear to be very different in various parts of the world. Genetics and Neonatal Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110016, India.
Fluocinonide 0-05% gel
Because of the potential risks we abandoned the development of these preparations. Reports suggesting that clobetasol propionate (’Der-
skin.
movate ’) has systemic effects 2,3led us to compare its systemic effect with that of two fluocinonide products (’Lidex’ cream andTopsyn ’ gel). Nine healthy male volunteers were admitted to hospital. 15 g. of the topical preparation was applied to the trunk, beginning in the evening and twice daily thereafter for a total of nine applications. There was never any occlusion by plastic film. Three volunteers were treated with each of the preparations. Plasma was obtained at 7.30 A.M. daily for 6 days and again on the 1 lth day, and cortisol levels were determined by the competitive protein-binding method of Murphy et al.4 Mean plasma-cortisol levels are shown in the accompanying figure. Complete suppression of plasma-cortisol levels was already evident 9-5 hours after the first application of clobetasol propionate and continued throughout the period of application. Sparkes and Wilson,5 in discussing adrenal suppression, state that " It is not expected that clobetasol propionate will behave differently " from other steroids. We
ISHWAR C. VERMA MEHARBAN SINGH.
1. Stevenson, A. C., Johnston, H. A., Stewart, M. I. P., Golding, D. R. Bull. Wld Hlth Org. 1966, 34, suppl. 1. 2. Ghosh, S., Bali, L. Ind. J. Child Hlth, 1963, 12, 448. 3. Khanna, K. K., Prasad, L. S. N. Ind. J. Pediat. 1967, 34, 63. 4. Aiyar, R. R., Agarwal, J. R. Ind. Pediat. 1969, 6, 729. 5. Raju, V. B. Personal communication. 6. Tibrewala, N. S., Pai, P. M. Ind. Pediat. 1974, 11, 403. 7. Hamerton, J. L. Human Cytogenetics; vol. II, p. 201. New York, 1971. 8. Hamerton, J. L., Ray, M., Abbot, J., Williamson, C., Ducasse, G. C. Can. med. Ass. J. 1972, 106, 776.
Average values 3 normal males per preparation Clobetasol propionate 0’05% ointment Fluocinonide 0’05% cream
cannot
agree.
Clinical Pharmacology Unit 404B, Hospital General de Mexico, Mexico City, Mexico.
E. ORTEGA.
Institute of Clinical Medicine,
Syntex Research, Palo Alto, California, U.S.A.
K. H. BURDICK E. J. SEGRE.
1. Lancet, 1967, ii, 1078. 2. Feiwel, M., Kelly, W. J. ibid. 1974, ii, 112. 3. Tan, R. Proc. R. Soc. Med. 1974, 67, 31. 4. Murphy, B. E. P., Engelberg, W, Pattee, C. J. J. clin. Endocr. Metab. 1963, 23, 293. 5. Sparkes, C. G., Wilson, L. Br. J. Derm. 1974, 90, 197.
impaired
G.A.B.A.
Miriam Marks Department of
Neurochemistry, Institute of Neurology, National Hospital, Queen Square,
DAVID M. BOWEN ALAN N. DAVISON.
London WC1N 3BG.
DOWN SYNDROME IN INDIA
SIR,-In a worldwide study of congenital malformations organised by the World Health Organisation no cases of Down syndrome were reported from India among 59,689 births in Bombay and Calcutta. There were no cases in 4141 births to Indian mothers in Kuala Lumpur, and only
ADRENAL SUPPRESSION BY CLOBETASOL
PROPIONATE SIR,—Until recently we have assumed that normal skin
constitutes an effective barrier to the absorption of corticosteroids. Application of potent steroids to diseased skin may produce transient suppression of pituitary-adrenal function, but the efficiency of the barrier increases with clinical improvement. Adrenal function recovers despite continuing steroid application. The increasingly effective combination of potent steroids and scientifically optimal bases threatens this physiological safety valve. We found that two of our topical corticosteroid preparations caused important adrenal suppression when applied to normal
1 affected child
was born to 3119 Indian mothers in In Singapore. all, there was only 1 child with Down to born 66,000 Indian mothers. These observasyndrome
FREQUENCY
OF
DOWN
SYNDROME
IN
SURVEYS
OF
NEWBORNS
IN INDIA
generated an impression that the frequency of Down syndrome in India is extremely low. This, however, is contrary to clinical experience of most paediatricians in India. Over 125 patients with Down syndrome have been evaluated in the genetics clinic in our hospital over a 4-year period. In the neonatal unit of our hospital, 4 infants with Down syndrome (confirmed by cytogenetic studies) have been detected among 3236 live births, giving a frequency of 1 per 809 live births (1-24 per 1000). Information from other Indian surveys of consecutive newborns gives a mean frequency of 1 per 1215 births (0-82 per 1000), with a range from 0-26 to 1-6 per 1000 births (see table). Excluding the data from Madras, which appears to have a low incidence, the mean frequency is 1-19 per 1000 births from among 35,325 births (range 0-73 to 1-6). The combined results of 9 surveys in Europe, North America, and Australiagave an average of 1 per 663 births (1-51 per 1000 births), with a range of 1-15 to 1-9 per 1000 births.
. &mid ot;
tions
5 chromosomal surveys of newborns in the U.K. and North America yielded a mean of 1-0 per 1000 births, with a range of 0 among 2081 births in London, Ontario, to 1-5 per 1000 births in Edinburgh. The frequency of Down syndrome, therefore, does not appear to be very different in various parts of the world. Genetics and Neonatal Unit, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110016, India.
Fluocinonide 0-05% gel
Because of the potential risks we abandoned the development of these preparations. Reports suggesting that clobetasol propionate (’Der-
skin.
movate ’) has systemic effects 2,3led us to compare its systemic effect with that of two fluocinonide products (’Lidex’ cream andTopsyn ’ gel). Nine healthy male volunteers were admitted to hospital. 15 g. of the topical preparation was applied to the trunk, beginning in the evening and twice daily thereafter for a total of nine applications. There was never any occlusion by plastic film. Three volunteers were treated with each of the preparations. Plasma was obtained at 7.30 A.M. daily for 6 days and again on the 1 lth day, and cortisol levels were determined by the competitive protein-binding method of Murphy et al.4 Mean plasma-cortisol levels are shown in the accompanying figure. Complete suppression of plasma-cortisol levels was already evident 9-5 hours after the first application of clobetasol propionate and continued throughout the period of application. Sparkes and Wilson,5 in discussing adrenal suppression, state that " It is not expected that clobetasol propionate will behave differently " from other steroids. We
ISHWAR C. VERMA MEHARBAN SINGH.
1. Stevenson, A. C., Johnston, H. A., Stewart, M. I. P., Golding, D. R. Bull. Wld Hlth Org. 1966, 34, suppl. 1. 2. Ghosh, S., Bali, L. Ind. J. Child Hlth, 1963, 12, 448. 3. Khanna, K. K., Prasad, L. S. N. Ind. J. Pediat. 1967, 34, 63. 4. Aiyar, R. R., Agarwal, J. R. Ind. Pediat. 1969, 6, 729. 5. Raju, V. B. Personal communication. 6. Tibrewala, N. S., Pai, P. M. Ind. Pediat. 1974, 11, 403. 7. Hamerton, J. L. Human Cytogenetics; vol. II, p. 201. New York, 1971. 8. Hamerton, J. L., Ray, M., Abbot, J., Williamson, C., Ducasse, G. C. Can. med. Ass. J. 1972, 106, 776.
Average values 3 normal males per preparation Clobetasol propionate 0’05% ointment Fluocinonide 0’05% cream
cannot
agree.
Clinical Pharmacology Unit 404B, Hospital General de Mexico, Mexico City, Mexico.
E. ORTEGA.
Institute of Clinical Medicine,
Syntex Research, Palo Alto, California, U.S.A.
K. H. BURDICK E. J. SEGRE.
1. Lancet, 1967, ii, 1078. 2. Feiwel, M., Kelly, W. J. ibid. 1974, ii, 112. 3. Tan, R. Proc. R. Soc. Med. 1974, 67, 31. 4. Murphy, B. E. P., Engelberg, W, Pattee, C. J. J. clin. Endocr. Metab. 1963, 23, 293. 5. Sparkes, C. G., Wilson, L. Br. J. Derm. 1974, 90, 197.
