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PHOSPHOKINASE ACTIVITY OF ERYTHROCYTES IN MONGOLISM
821 whether the aneuploid cells were lymphocytes or thyroid epithelial cells, or whether the chromosome anomaly was con-
genital or acquired. Fialkow,7 after considering
of evidence relating chromosome abnormalities to the occurrence of thyroid autoantibodies, suggested that a " parental immunological aberration predisposes to the aneuploidy (in either mitosis or meiosis): or perhaps the two are noncausally related through a third factor capable of causing both, such as a virus or an endocrine dysfunction " rather than that the chromosome abnormality predisposes to the immunological aberration. N. B. ATKIN Department of Cancer Research, Mount Vernon Hospital, MARION C. BAKER. Northwood, Middlesex. a
large body
PHOSPHOKINASE ACTIVITY OF ERYTHROCYTES IN MONGOLISM SIR,-The controversy over the relation of enzyme activity to gene action and cellular metabolism in mongolism (Down’s syndrome) has been reopened by the report of Dr. Baikie and his colleagues (Feb. 20). In their study of red-cell glycolytic enzymes in patients with Down’s syndrome we are impressed by the finding of increased activity of only one enzyme (phosphohexokinase), with normal activity of 12 other enzymes. They suggest that this may be evidence of a direct effect of the genes on chromosome 21 rather than a reflection of a general and non-specific derangement of erythrocyte metabolism. The essence of their argument HaeMATOLOGICAL SURVEY AND E.G.O.T. ACTIVITY OF
12
12
MONGOLS AND
MATCHED CONTROLS FROM THE SAME INSTITUTION
has been shown previously -1-1 to be one of the most sensitive indicators of red-cell age. The results of these studies are given in the accompanying table. It is evident that E.G.O.T. activity in the mongols is significantly elevated when expressed in relation to red cells but not when related to haemoglobin. We interpret these findings thus: (1) in the presence of macrocytosis, it seems more reasonable to express enzyme activity as a function of the unit cell rather than of a totally unrelated index such as hxmoglobin; (2) the combination of large erythrocytes and increased E.G.O.T. activity suggests a younger mean cell-age of the erythrocyte population in Down’s syndrome. The cause for this is at present under investigation.
It would be
interesting to see whether the expression of enzyme activity in relation to red-cell count alters the results obtained in the other 12 glycolytic enzymes studied by Dr. Baikie and his colleagues. We wish to acknowledge the assistance of the Elwyn in the study of these patients.
School, Elwyn,
Pennsylvania,
J. LAWRENCE NAIMAN
Department of Pediatrics, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
FRANK A. OSKI WILLIAM J. MELLMAN.
DIAGNOSIS OF BRONCHIAL ASTHMA SIR,-The diagnosis of bronchial asthma is usually confirmed by auscultation of both lung-fields. This requires that the patient should undress. For some time I have made the diagnosis in, as well as followed the progress of, asthmatic patients by listening with my stethoscope over both cheeks. An asthmatic patient may complain of wheezing, and on listening to the lungs both may be clear. If, on the other hand, one listens with a stethoscope over either cheek, wheezes may be picked up. Eastern Region Medical Centre, Uwani Enugu, Nigeria.
N. E. OKEKE.
REACTION TO CHLORHEXIDINE AND CETRIMIDE
SIR,-Dr. Birdwood’s letter (March 20) describes a of hypersensitivity to’Savlon’, confirmed by a patch-test using a solution of 0-67% in water. In this works medical department, serving a population of 4000, we have used 1% savlon for 4 years for some 16,000 minor injuries, but we have had only one case of case
skin reaction. rests on the failure to demonstrate increased activity of the other enzymes studied. In support they cite previous work8 showing that, although the leucocytes of mongols have increased activity of galactose-1-phosphate uridyl transferase and glucose6-phosphate dehydrogenase, the erythrocytes do not show this increase. Others, however, have shown that the activity of these 10 enzymes is increased in erythrocytes.9 We have obtained data that suggest another factor which may influence the interpretation of the results of erythrocyte-enzyme activity in patients with Down’s syndrome, and possibly explain the failure of Dr. Baikie and others to detect increases in the activity of other enzymes in these patients. In a h2ematological survey of 12 mongols from an institution, we found a significant macrocytosis, reflected in increased packed-cell volume and mean corpuscular volume in comparison with matched controls from the same institution. There was no evidence of deficiency of vitamin B,,, folic acid, pyridoxine, or iron to explain these differences. To determine whether the observed macrocytosis was attributable to a younger mean cellage, erythrocyte glutamic-oxaloacetic transaminase (E.G.O.T.) activity was determined on carefully washed cells. This enzyme 7. Fialkow, P. J. ibid., 1964, i, 474. 8. Hsia, D. Y., Inouye, T., Wong, P., South, A. New Engl. J. Med. 1964, 270, 1085. 9. Won, G. N., Bergren, W. R., Donnell, G. N. Clin. chim. Acta, 1964, 10.
10, 337. Rosner, F., Ong, B. H., Mahanand, D., Paine, R. S., Jacobson, C. B. Lancet, 1964, ii, 1345.
A 53-year-old man, believed to be hypersensitive to neomycin, cut his shin and the wound was cleaned with savlon. He developed a localised dermatitis with subcutaneous oedema which soon got better. Patch-testing with the 1%solution of savlon and with a control dressing for 24 hours resulted in an area of erythema with vesiculation. Having used so strong a solution the possibility remains that the response was one of primary irritation and not of hypersensitivity.
We have continued trouble.
to
use
savlon without further
Medical Department, Hoffmann Manufacturing Company, Ltd., Chelmsford, Essex.
K. H. NICKOL.
SIR,-Dr. Birdwood has described an unusually severe sensitivity reaction of a kind we have not previously encountered. The fact that the patient had tolerated 2 0o cetrimide does not necessarily " suggest that the reaction was to chlorhexidine digluconate ". MacIntyre 12 described a sensitivity reaction to ’Savlon patch-testing revealed to be due to a relatively minute content of perfume. Reactions to chlorhexidine appear to be very rare; in view of this and of the possibility that one of the minor constituents of Savlon may be responsible, we feel it is which
11. 12.
Sass, M. D., Vorsanger, E., Spear, P. W. Clin. chim. Acta, 1964, 10 ,21. I. Brit. med. J. 1963, i, 953.
MacIntyre,
genital or acquired. Fialkow,7 after considering
of evidence relating chromosome abnormalities to the occurrence of thyroid autoantibodies, suggested that a " parental immunological aberration predisposes to the aneuploidy (in either mitosis or meiosis): or perhaps the two are noncausally related through a third factor capable of causing both, such as a virus or an endocrine dysfunction " rather than that the chromosome abnormality predisposes to the immunological aberration. N. B. ATKIN Department of Cancer Research, Mount Vernon Hospital, MARION C. BAKER. Northwood, Middlesex. a
large body
PHOSPHOKINASE ACTIVITY OF ERYTHROCYTES IN MONGOLISM SIR,-The controversy over the relation of enzyme activity to gene action and cellular metabolism in mongolism (Down’s syndrome) has been reopened by the report of Dr. Baikie and his colleagues (Feb. 20). In their study of red-cell glycolytic enzymes in patients with Down’s syndrome we are impressed by the finding of increased activity of only one enzyme (phosphohexokinase), with normal activity of 12 other enzymes. They suggest that this may be evidence of a direct effect of the genes on chromosome 21 rather than a reflection of a general and non-specific derangement of erythrocyte metabolism. The essence of their argument HaeMATOLOGICAL SURVEY AND E.G.O.T. ACTIVITY OF
12
12
MONGOLS AND
MATCHED CONTROLS FROM THE SAME INSTITUTION
has been shown previously -1-1 to be one of the most sensitive indicators of red-cell age. The results of these studies are given in the accompanying table. It is evident that E.G.O.T. activity in the mongols is significantly elevated when expressed in relation to red cells but not when related to haemoglobin. We interpret these findings thus: (1) in the presence of macrocytosis, it seems more reasonable to express enzyme activity as a function of the unit cell rather than of a totally unrelated index such as hxmoglobin; (2) the combination of large erythrocytes and increased E.G.O.T. activity suggests a younger mean cell-age of the erythrocyte population in Down’s syndrome. The cause for this is at present under investigation.
It would be
interesting to see whether the expression of enzyme activity in relation to red-cell count alters the results obtained in the other 12 glycolytic enzymes studied by Dr. Baikie and his colleagues. We wish to acknowledge the assistance of the Elwyn in the study of these patients.
School, Elwyn,
Pennsylvania,
J. LAWRENCE NAIMAN
Department of Pediatrics, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
FRANK A. OSKI WILLIAM J. MELLMAN.
DIAGNOSIS OF BRONCHIAL ASTHMA SIR,-The diagnosis of bronchial asthma is usually confirmed by auscultation of both lung-fields. This requires that the patient should undress. For some time I have made the diagnosis in, as well as followed the progress of, asthmatic patients by listening with my stethoscope over both cheeks. An asthmatic patient may complain of wheezing, and on listening to the lungs both may be clear. If, on the other hand, one listens with a stethoscope over either cheek, wheezes may be picked up. Eastern Region Medical Centre, Uwani Enugu, Nigeria.
N. E. OKEKE.
REACTION TO CHLORHEXIDINE AND CETRIMIDE
SIR,-Dr. Birdwood’s letter (March 20) describes a of hypersensitivity to’Savlon’, confirmed by a patch-test using a solution of 0-67% in water. In this works medical department, serving a population of 4000, we have used 1% savlon for 4 years for some 16,000 minor injuries, but we have had only one case of case
skin reaction. rests on the failure to demonstrate increased activity of the other enzymes studied. In support they cite previous work8 showing that, although the leucocytes of mongols have increased activity of galactose-1-phosphate uridyl transferase and glucose6-phosphate dehydrogenase, the erythrocytes do not show this increase. Others, however, have shown that the activity of these 10 enzymes is increased in erythrocytes.9 We have obtained data that suggest another factor which may influence the interpretation of the results of erythrocyte-enzyme activity in patients with Down’s syndrome, and possibly explain the failure of Dr. Baikie and others to detect increases in the activity of other enzymes in these patients. In a h2ematological survey of 12 mongols from an institution, we found a significant macrocytosis, reflected in increased packed-cell volume and mean corpuscular volume in comparison with matched controls from the same institution. There was no evidence of deficiency of vitamin B,,, folic acid, pyridoxine, or iron to explain these differences. To determine whether the observed macrocytosis was attributable to a younger mean cellage, erythrocyte glutamic-oxaloacetic transaminase (E.G.O.T.) activity was determined on carefully washed cells. This enzyme 7. Fialkow, P. J. ibid., 1964, i, 474. 8. Hsia, D. Y., Inouye, T., Wong, P., South, A. New Engl. J. Med. 1964, 270, 1085. 9. Won, G. N., Bergren, W. R., Donnell, G. N. Clin. chim. Acta, 1964, 10.
10, 337. Rosner, F., Ong, B. H., Mahanand, D., Paine, R. S., Jacobson, C. B. Lancet, 1964, ii, 1345.
A 53-year-old man, believed to be hypersensitive to neomycin, cut his shin and the wound was cleaned with savlon. He developed a localised dermatitis with subcutaneous oedema which soon got better. Patch-testing with the 1%solution of savlon and with a control dressing for 24 hours resulted in an area of erythema with vesiculation. Having used so strong a solution the possibility remains that the response was one of primary irritation and not of hypersensitivity.
We have continued trouble.
to
use
savlon without further
Medical Department, Hoffmann Manufacturing Company, Ltd., Chelmsford, Essex.
K. H. NICKOL.
SIR,-Dr. Birdwood has described an unusually severe sensitivity reaction of a kind we have not previously encountered. The fact that the patient had tolerated 2 0o cetrimide does not necessarily " suggest that the reaction was to chlorhexidine digluconate ". MacIntyre 12 described a sensitivity reaction to ’Savlon patch-testing revealed to be due to a relatively minute content of perfume. Reactions to chlorhexidine appear to be very rare; in view of this and of the possibility that one of the minor constituents of Savlon may be responsible, we feel it is which
11. 12.
Sass, M. D., Vorsanger, E., Spear, P. W. Clin. chim. Acta, 1964, 10 ,21. I. Brit. med. J. 1963, i, 953.
MacIntyre,