322 Acute tubular necrosis usually shows a spontaneous recovery up to the first 3 weeks post transplantation. Rejection episodes respond to prednisone bolus, usually with resumption of function. However, in the mixed form the situation is complex and the diagnosis is difficult, so most transplantation centres give prednisone if the graft fails to function, as Kreis et al. did. The observations made by the Hopital Necker transplantation team on the onset and frequency of renal-failure episodes in prednisone pretreated and non-pretreated patients are of interest, but measurements made do not seem suitable to distinguish the two forms of graft failure; and the results do not quite support the conclusions drawn. The concept of steroid dependence and independence in renal-failure episodes seems to
quite profound changes in other aminoacids in both the model and the human.5,6 The effect of manipulating maternal aminoacid levels in the organogenetic phase of fetal animal development may be worth studying if it has not already been done. Otherwise it seems only a matter of time until more human pregnancies are documented. Among them there may be some which have been concealed by the mother until the 20th week (as in B): perhaps she was wiser than we know, but it would be foolish to take her advice.
cause
rat
Department of Child Life and Health, University of Edinburgh,
Edinburgh
EH9 1UW
JAMES W. FARQUHAR
need further investigating.
First Department of Surgery and Institute of Experimental Surgery, University Medical School of Szeged, H-6701 Szeged, Hungary
CALCULATION AND THE RIGHT HEMISPHERE G. HORPACSY
CONCEPTION IN A PHENYLKETONURIC WOMAN
SiR,-The detailed study of a single case by Dr Smith and her colleagues (Jan. 6, p. 17) naturally interests me.1,2 The issue is crucial to young women who, as a result of previous dietary care, are now fit to bear children. The jig-saw must fall into place during the next few years but the pieces may not yet be ready to interlock. P.K.U. itself is a conglomerate3 of metabolic faults causing variable hyperphenylalaninxmia in all cases and P.K.U. in some. Some untreated affected women have malformed and/or brain-damaged fetuses, while an unknown proportion (perhaps very small) do not. The one fetus now described (A) was grossly deformed despite dietary control of the mother from about the 6th week after conception. My one case (B) reports regularly for review, and, in his 9th year, attends a normal school and shows obesity as his only abnormality. P.K.U. female A probably had a serum-phenylalanine between 1800 and 2100 mol/1 at conception and B’s was probably around 1500. Both consistently excreted phenylketones in their urine. A had an i.Q. of about 79, B of 55. A was 21 years of age, B was 24. A was treated from 7 weeks’ gestation and B’from about 20 weeks. In A, between 7 and 10 weeks gestation, dietary manipulation maintained the average serumphenylalanine around 600 mol/1 and between 10 and 21 weeks it was about 378. During this same period B’s aminoacid intake was not manipulated and presumably averaged 1500 or more. I imagine that no-one knows why B’s fetus was "protected" and why A’s was so heavily damaged. Might some linked genetic factor have predisposed A to it? Was A’s higher serumphenylalanine responsible? Could manipulation of aminoacids in the diet be harmful in the first trimester, and is there an animal model which might answer this? P.K.u. babies can develop alarming signs if overtreated, and at an international symposium in Tel-Aviv in 1971 there was considerable anxiety about morbidity and even mortality caused by hypophenylalaninxmia. I had occasion myself6 to suspect the harmful effects of hypophenylalaninsemia on the brain of a phenylketonuric baby overzealously treated between the postnatal ages of 2 weeks and 6 months. During this time the serum level was commonly well below 120 limola. It was then kept in the normal range, but Dr C. M. Drillien estimated his D.Q. as 62 at 11 months and the patient has spent his life in a hospital for the mentally handicapped. There is no evidence of temporary maternal hypophenylalaninxmia in A and I assume that monitoring was frequent enough to have excluded it. Fetal levels, however, can and do differ from maternal ones, and iatrogenic aminoacid imbalance created by hyperphenylalaninaemia may 1. Farquhar, J. W., Miller, M. C., Lindsay, G. Br. med. J. 1971, i, 46. 2. Farquhar, J. W. Archs Dis. Childh. 1974, 49, 205. 3. Niederwieser, A., Curtius, H-C., Bettoni, O., Bieri, J., Schirchs, B., Viscontini, M., Schaub, J. Lancet, 1979, i, 131. 4. Farquhar, J. W., Richmond, J., Tait, H. P. Clin. Pediat. 1963, 2, 504.
SIR,-Clinical evidence has often indicated that lesions of the left rather than the right hemisphere produce deficits in calculating ability, known as "acalculia".’,2 In 1972 Dimond and Beaumont3 published a report which indicated that the right hemisphere showed a significant superiority in calculation, particularly subtraction. The study was done on normal subjects, but an important factor was that of response output (i.e., the way subjects were asked to respond). This was non-verbal, with subjects pressing a switch to indicate their response. The next logical step therefore was to test the hypothesis of right-hemisphere superiority on patients with unilateral brain damage. We have studied patients with left hemisphere and right hemisphere damage to determine effects on calculation ability when means other than verbal output were used. 18 patients from the University Hospital of Wales neurology and neurosurgery wards took part. 5 were controls, (they had back pain and other peripheral neurological disorders); and 6 with right-sided lesions and 7 with left-sided damage were examined. There were 10 males and 8 females. A portable projection apparatus4 was used to flash stimuli to the visual fields. Three pairs of digits were presented successively to the patient (e.g., 84-71=13). The subject’s task was to indicate whether or not the third number was a correct subtraction of the second from the first. Half of the 24 trials were correct, the other half incorrect. The complete sequence was flashed either to the right or the left visual field. The exposuretime for each pair of digits was 300 ms. The patient indicated if the answer was true or false by nodding or shaking the head. The percentage errors are presented in the table. An analysis of variance shows the side of damage to be a highly signifithe performance of the rightcant factor (F=10.92, Por
68 fl) resulted in 13 of the 14 severe cases being correctly designated by both the discriminant function and the R.B.C. count, with the remaining severe case being misclassified by both. Of the 30 mild cases, the discriminant function incorrectly designated 16 (53%) and the R.B.C. count 18 (60%), with good concordance between the two determinants for the cases which they wrongly allocated. The new discriminant function performed less well than both these methods, suggesting that the inclusion of the ac-thalassaemia data had reduced the discriminating value of the red cell indices. We conclude that the discriminant function is no more useful than the R.B.c. count alone in distinguishing between the microcytosis of iron deficiency and that of &bgr;-thalassaemia trait; that both determinants reliably rule out a diagnosis of iron deficiency but cannot reliably exclude a diagnosis of p-thalassaemia trait, both being unreliable in pregancy, and that the discriminant function and the R.B.C. count are equally poor at distinguishing the blood counts of the milder forms of M-thalassxmia trait from those of iron deficiency. We thank Dr I. Chanarin for his advice and
suggestions.
Department of Hæmatology Central Middlesex
Hospital, DIANA M. WALFORD
London NW1 0
Department of Social University of Oxford
and
Community Medicine,
of Hæmatology Northwick Park Hospital Clinical Research Centre, Harrow, Middlesex
K. MCPHERSON
Derpatment
3. 4.
ROSEMARY DEACON
Walford, D. M., Deacon, R. ibid. 1976, 34, 193. Weatherall, D. J., Clegg, J. B. The Thalassæmia Syndromes; p. 233. Oxford, 1972.
quite profound changes in other aminoacids in both the model and the human.5,6 The effect of manipulating maternal aminoacid levels in the organogenetic phase of fetal animal development may be worth studying if it has not already been done. Otherwise it seems only a matter of time until more human pregnancies are documented. Among them there may be some which have been concealed by the mother until the 20th week (as in B): perhaps she was wiser than we know, but it would be foolish to take her advice.
cause
rat
Department of Child Life and Health, University of Edinburgh,
Edinburgh
EH9 1UW
JAMES W. FARQUHAR
need further investigating.
First Department of Surgery and Institute of Experimental Surgery, University Medical School of Szeged, H-6701 Szeged, Hungary
CALCULATION AND THE RIGHT HEMISPHERE G. HORPACSY
CONCEPTION IN A PHENYLKETONURIC WOMAN
SiR,-The detailed study of a single case by Dr Smith and her colleagues (Jan. 6, p. 17) naturally interests me.1,2 The issue is crucial to young women who, as a result of previous dietary care, are now fit to bear children. The jig-saw must fall into place during the next few years but the pieces may not yet be ready to interlock. P.K.U. itself is a conglomerate3 of metabolic faults causing variable hyperphenylalaninxmia in all cases and P.K.U. in some. Some untreated affected women have malformed and/or brain-damaged fetuses, while an unknown proportion (perhaps very small) do not. The one fetus now described (A) was grossly deformed despite dietary control of the mother from about the 6th week after conception. My one case (B) reports regularly for review, and, in his 9th year, attends a normal school and shows obesity as his only abnormality. P.K.U. female A probably had a serum-phenylalanine between 1800 and 2100 mol/1 at conception and B’s was probably around 1500. Both consistently excreted phenylketones in their urine. A had an i.Q. of about 79, B of 55. A was 21 years of age, B was 24. A was treated from 7 weeks’ gestation and B’from about 20 weeks. In A, between 7 and 10 weeks gestation, dietary manipulation maintained the average serumphenylalanine around 600 mol/1 and between 10 and 21 weeks it was about 378. During this same period B’s aminoacid intake was not manipulated and presumably averaged 1500 or more. I imagine that no-one knows why B’s fetus was "protected" and why A’s was so heavily damaged. Might some linked genetic factor have predisposed A to it? Was A’s higher serumphenylalanine responsible? Could manipulation of aminoacids in the diet be harmful in the first trimester, and is there an animal model which might answer this? P.K.u. babies can develop alarming signs if overtreated, and at an international symposium in Tel-Aviv in 1971 there was considerable anxiety about morbidity and even mortality caused by hypophenylalaninxmia. I had occasion myself6 to suspect the harmful effects of hypophenylalaninsemia on the brain of a phenylketonuric baby overzealously treated between the postnatal ages of 2 weeks and 6 months. During this time the serum level was commonly well below 120 limola. It was then kept in the normal range, but Dr C. M. Drillien estimated his D.Q. as 62 at 11 months and the patient has spent his life in a hospital for the mentally handicapped. There is no evidence of temporary maternal hypophenylalaninxmia in A and I assume that monitoring was frequent enough to have excluded it. Fetal levels, however, can and do differ from maternal ones, and iatrogenic aminoacid imbalance created by hyperphenylalaninaemia may 1. Farquhar, J. W., Miller, M. C., Lindsay, G. Br. med. J. 1971, i, 46. 2. Farquhar, J. W. Archs Dis. Childh. 1974, 49, 205. 3. Niederwieser, A., Curtius, H-C., Bettoni, O., Bieri, J., Schirchs, B., Viscontini, M., Schaub, J. Lancet, 1979, i, 131. 4. Farquhar, J. W., Richmond, J., Tait, H. P. Clin. Pediat. 1963, 2, 504.
SIR,-Clinical evidence has often indicated that lesions of the left rather than the right hemisphere produce deficits in calculating ability, known as "acalculia".’,2 In 1972 Dimond and Beaumont3 published a report which indicated that the right hemisphere showed a significant superiority in calculation, particularly subtraction. The study was done on normal subjects, but an important factor was that of response output (i.e., the way subjects were asked to respond). This was non-verbal, with subjects pressing a switch to indicate their response. The next logical step therefore was to test the hypothesis of right-hemisphere superiority on patients with unilateral brain damage. We have studied patients with left hemisphere and right hemisphere damage to determine effects on calculation ability when means other than verbal output were used. 18 patients from the University Hospital of Wales neurology and neurosurgery wards took part. 5 were controls, (they had back pain and other peripheral neurological disorders); and 6 with right-sided lesions and 7 with left-sided damage were examined. There were 10 males and 8 females. A portable projection apparatus4 was used to flash stimuli to the visual fields. Three pairs of digits were presented successively to the patient (e.g., 84-71=13). The subject’s task was to indicate whether or not the third number was a correct subtraction of the second from the first. Half of the 24 trials were correct, the other half incorrect. The complete sequence was flashed either to the right or the left visual field. The exposuretime for each pair of digits was 300 ms. The patient indicated if the answer was true or false by nodding or shaking the head. The percentage errors are presented in the table. An analysis of variance shows the side of damage to be a highly signifithe performance of the rightcant factor (F=10.92, Por
68 fl) resulted in 13 of the 14 severe cases being correctly designated by both the discriminant function and the R.B.C. count, with the remaining severe case being misclassified by both. Of the 30 mild cases, the discriminant function incorrectly designated 16 (53%) and the R.B.C. count 18 (60%), with good concordance between the two determinants for the cases which they wrongly allocated. The new discriminant function performed less well than both these methods, suggesting that the inclusion of the ac-thalassaemia data had reduced the discriminating value of the red cell indices. We conclude that the discriminant function is no more useful than the R.B.c. count alone in distinguishing between the microcytosis of iron deficiency and that of &bgr;-thalassaemia trait; that both determinants reliably rule out a diagnosis of iron deficiency but cannot reliably exclude a diagnosis of p-thalassaemia trait, both being unreliable in pregancy, and that the discriminant function and the R.B.C. count are equally poor at distinguishing the blood counts of the milder forms of M-thalassxmia trait from those of iron deficiency. We thank Dr I. Chanarin for his advice and
suggestions.
Department of Hæmatology Central Middlesex
Hospital, DIANA M. WALFORD
London NW1 0
Department of Social University of Oxford
and
Community Medicine,
of Hæmatology Northwick Park Hospital Clinical Research Centre, Harrow, Middlesex
K. MCPHERSON
Derpatment
3. 4.
ROSEMARY DEACON
Walford, D. M., Deacon, R. ibid. 1976, 34, 193. Weatherall, D. J., Clegg, J. B. The Thalassæmia Syndromes; p. 233. Oxford, 1972.
