42 DAY-TRANSFUSION CENTRE FOR THALASSÆMICS SIR,—The paper by Dr Vance (April 26, p. 967) pin-

pointing loss of school-time in thalassaemics undergoing regular blood-transfusions is exceedingly important. I should like to report our own method for combating this problem.

Ftt. 2—Negativety stained in8uenza-like virus ( 130,000).

Fig. 3—Negativety stained influenza-like filament

(

130,000).

The Whittington Hospital currently treats nineteen thalassaemic children, transfusing them at approximately 6-weekly intervals (8 transfusions per year). It was realised many years ago that this could significantly encroach on school and home life unless streamlined for the benefit of the patients. Consequently, the children are seen in a special outpatient clinic, 3 or 4 each Monday morning between 9 and 10 A.M. The haematology laboratory kindly measures haemoglobin before they are seen by the pa:diatrician, who then examines them and cross-matches blood as necessary. They are back at school between 9.30 and 10.30 A.M. Transfusion is carried out on Friday or Saturday nights starting at about 8 P.M., the children thus sleeping through the major part of the transfusion. They go home first thing in the morning, thus missing no further schooling and little weekend home life. The following evening they come to the ward to have a post-transfusion h2emoglobin estimation by the s.H.o. on duty. This regimen is possible as all our patients live within a few miles of the hospital. With 8 transfusions a year they will miss, hopefully, no more than 8 hours of school-time for their routine visits. The rest of our treatment is similar to that of the Victoria group, though our chelation is more intensive-3 g. of desferrioxamine per pint of blood transfused and 750-1000 mg. desferrioxamine intramuscularly per day. With this regimen our eldest children are in negative iron balance.1 Pædiatric Unit, Whittington Hospital,

Fig. 4—Elongated structures in nucleus

and

cytoplasm (65,000).

Electron microscopy revealed myxovirus-like bodies in uncentrifuged fluid harvests (figs. 2 and 3). The viral particles in thin sections averaged 85 nm. in diameter as did the negatively stained viral filaments. Surface spikes were present on both forms. Nucleocapsid strands were abundant in the cytoplasm, and elongated structures 50-70 nm. in diameter occurred frequently in the nucleus but only rarely in the cytoplasm (fig. 4). The cytopathic changes seen in cultures stained with hæmatoxylin and eosin were quite unlike those of known paramyxoviruses inoculated by us into simian kidney cells. In 1966 Harwin et al.recorded the presence of cytoplasmic basophilic inclusions and nuclear eosinophilic masses in vervet monkey kidney cells infected with strains of influenza B virus. These workers did not describe nucleolar changes, but review of stained vervet kidney cultures infected with influenza B virus recovered from one of us (H. M.) a number of years ago showed that eosinophilic changes in

the nucleoli, similar to those now described, were present although to a lesser extent. Further characterisation studies are in progress, but on the basis of the distinctive cytopathology and the electronmicroscopy findings, the baboon isolate appears to belong to the myxovirus group. We thank Ms A. Golston for technical assistance. This study funded in part by U.S. Pubhc Health Service grants RROO361 and RR05519, and W.H.O. grants Z2 181 27and V4 181 38. This laboratory serves as the N.I.H. W.H.O. Collaborating Centre for Reference and Research in Sinnao Viruses. was

Southwest Foundation for Research and Education, P.O Box 28147, San Antonio, Texas 78284, U S.A. 1.

H. MALHERBE M. STRICKLANDCHOLMLEY G. C. SMITH.

Harwin, R M , Joesting, A , Gear,J H S Lancet, 1966,

i,

1218.

London N19 5NF.

NEIL MCINTOSH.

BLOOD-PRESSURE READING

SIR,—The measurement of blood-pressure is one of the important parts of clinical examination, and it is

most

essential that a standard procedure is followed. The various technical details of blood-pressure reading are clearly laid down. However, it is less well known that the reading of blood-pressure in the right arm is often slightly higher than in the left, and differences of 2 mm. to 10 mm. Hg mercury are seen. It is even more important that the endpoint of the diastolic reading is often clearer and more easily recognised on the left side. The reason for this must be the difference in the origins of the subelavian arteries. It is therefore recommended that the blood-pressure is always taken in the left arm. Wanstead Hospital, London E11.

ERIC FRANKEL.

SUPEROXIDE DISMUTASE IN DOWN SYNDROME

SIR,—Your editorial on metabolic disorders in Down syndromeI suggests that a convincing gene-dosage effect in trisomy 21 has never been reported. Later, however, Sinet et al.’ demonstrated that cytoplasmic superoxidedismutase activity (S.O.D.A.) was increased in the erythrocytes of 10 trisomy-21 children compared with 10 controls.* 1. 2. 3. 4.

Modell, C. B., Beek, J. Ann. N.Y. Acad. Sci. 1974, 232, 201. Lancet, 1974, ii, 1554. Sinet, P.-M.,Allard, D.,Lejeune,J.,Jérôme,H.ibid. 1975,i,276. Sinet, P.-M., Allard, D., Lejeune, J., Jérôme,H. C. r. Acad. Sci. Paris, 1974,278,3267.

43

0

Relative erythrocyte

40

20

120 80 140 60 100 RELATIVE S.O.D. CONCENTRATION

transferase8 red-cell phosphohexokinase,9,10 and red-cell i

The

elevation

in catechol-0-methyl-transferase." alkaline phosphatase is non-specific, occurring also in other trisomies and in infections.12 Furthermore, there is no real evidence that the gene for any of these enzymes is localised on chromosome 21, and the excess in enzyme activity cannot be explained directly on the basis of genedosage effect. However, the gene for S.O.D. has been assigned to chromosome 21 by linkage analysis using somatic-cell!hybrids.13 Thus, the most tempting conclusion is that the high S.O.D.A. in trisomy 21 is the consequence of a gene-dosage effect. 4. Benson, P. F. Lancet, 1975, i, 584. 5. Frants, R. R., Eriksson, A. W. 16th Dutch Federative Meeting 1975,

8. 9. 10. 11.

12. 13.

180

200

(cytoplasmic) superoxide-dismutase concentration in Down syndrome patients and two control groups.

They concluded that the increase in S.O.D.A. is the result of a gene-dosage effect. Benson4 calls this interpretation into question. He concludes that enhancement of enzyme activity in erythrocytes and leucocytes is not convincing evidence of a gene-dosage effect in trisomic conditions. We have developed a quantitative immunological technique (Mancini) to determine the amount of S.O.D. protein in human material, including red cells. The s.o.D. concentration was correlated with haemoglobin, with a haemolysate pool from laboratory personnel as standard.5,6s We have investigated 33 institutionalised Down syndrome patients aged 4-29. So far 22 of them have been karyotyped and were found to be regularly trisomic 21. Two control groups were studied. The first consisted of mentally retarded but chromosomally normal patients from the same wards, matched for age and sex. As a second control group, staff from the same wards was investigated. Down syndrome patients have, on average, 40% more S.O.D.A. in the erythrocytes than both control groups (see accompanying figure). The accordance with the results of Sinet et awl. is obvious, although it has to be borne in mind that they used a colorimetric technique measuring the capacity of s.o.D. to inhibit superoxide radical-mediated reduction of a synthetic acceptor, whereas we are determining the s.o.D. protein concentration. In trisomy 21 an elevation has been found in the activity of many other leucocyte-alkalineenzymes-e.g., phosphatase,’’ whole-blood galactose-1-phosphate-uridyl-

6. 7.

160

p. 208. Frants, R. R. Unpublished. Alter, A. A., Lee, S. L., Pourfar, M., Dobkin, G. J. clin. Invest. 1962, 41, 1341. Brandt, N. J., Frøland, A., Mikkelsen, M., Nielsen, A., Tolstrup, N. Lancet, 1963, ii, 700. Baikie, A. G., Loder, P. B., deGruchy, G. C., Pitt, D. B. ibid. 1965, i, 412. Bartels, H., Kruse, K. Humangenetik, 1968, 6, 305. Gustavson, K.-H., Wetterberg, L., Bäckström, M., Ross, S. B. Clin. Genet. 1973, 4, 279. Trubowitz, S., Kirman, D., Masek, B. Lancet, 1962, ii, 486. Tan, Y. H., Tischfield, J., Ruddle, F. H.J. exp. Med. 1973, 137, 317.

A physiological role of S.O.D. is to dismutate the reactive superoxide radicals. Such radicals have been shown to be involved in defence against bacteria. Increased S.O.D.A. could lower the concentration of superoxide radicals, resulting in the increased susceptibility to bacterial and viral infections 6 frequently encountered in Down syndrome.

Further studies will show whether the S.O.D. concentration is influenced by a triple-gene dosage effect or by secondary factors, such as a generally disturbed protein synthesis or a younger mean cell-age, reflected in a slight macrocytosis in a number of our Down syndrome subjects. Institute of Human Genetics, Free University of Amsterdam, The Netherlands.

R. R. FRANTS A. W. ERIKSSON.

Huize " Maria Roepaan ", Institute for Observation and Treatment of Mentally Retarded, Ottersum, The Netherlands.

P. H. JONGBLOET A. J. HAMERS.

Obituary WILLIAM STUART McRAE CRAIG M.D.Edin., B.Sc.Glasg., F.R.C.P., F.R.C.P.E., F.R.S.E.

Prof. W. S. M. Craig, professor emeritus of paediatrics and child health in the University of Leeds, died on June 21 at the age of 72. He came He was the

unusual path to the chair in Leeds. a much-loved general practitioner in Bingley, Yorkshire, and after obtaining his B.sc. (in naval architecture) at Glasgow University in 1924, he worked for a time in a Clydeside shipyard. He turned later to medicine and made rapid progress after graduating M.B. in 1930 at Edinburgh University. By 1936 he had published several valuable papers, and was an assistant paediatrician in Edinburgh under Prof. Charles McNeil; but there was little hope of early advancement, and young paediatricians had small incomes in those days. He joined the Ministry of Health in 1936, and spent 10 years there, chiefly as a hospital medical officer. In 1946 he published Child and Adolescent Life in Health and Disease. This was the first book of its kind on social pxdiatrics and was soon considered essential reading for budding paediatricians.

by

son

an

of

When he was appointed to the chair at Leeds University in 1946, he had a tiny room in the General Infirmary and plenty of patients in four hospitals, but no department of pxdiatrics in the modern sense, so he had to make a start from very little, in a city without a children’s hospital.

Letter: Superoxide dismutase in Down syndrome.

42 DAY-TRANSFUSION CENTRE FOR THALASSÆMICS SIR,—The paper by Dr Vance (April 26, p. 967) pin- pointing loss of school-time in thalassaemi...
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