1378 (2) What medication
was
prescribed ? Nearly all therapeutic
agents have actions additional to that of lowering arterial pressure. (3) What was the evidence submitted to the patients that reducing arterial pressures of 95-100 mm. Hg diastolic, measured of course under similar circumstances, would reduce morbidity and mortality ?
Unless there is evidence of which I am ignorant, I am that I would be a non-complier, however convenient it was made for me to attend a physician. sure
The Grange, Moulsford-on-Thames, Berkshire OX10 9JD.
GEORGE PICKERING.
POTENTIAL VARIANTS OF PHENYLKETONURIA SIR,-The syndrome in which children have biochemical manifestations of phenylketonuria and additional neurological problems, but have normal liver phenylalanine hydroxylase activity,l.2 is arousing interest among those studying metabolic diseases. We are preparing data for publication which indicate that mitochondria have a potential role to play in the regulation of aromatic aminoacid hydroxylases. Addition of mitochondria to the soluble fraction of rat liver homogenate results in inhibition of phenylalanine-hydroxylase activity. This is possible even in the presence of adequate oxygen because mitochondria oxidise tetrahydropterins over cytochrome c and cytochrome oxidase, thereby diminishing the amount of active cofactor available for the hydroxylation reaction. It is clear from studies of other metabolic disorders-for example, methylmalonic aciduria 3-that different genetic mutations involving the apoenzyme or cofactor metabolism may result in a similar clinical picture. It has been postulated that P.K.U. patients with normal phenylalanine hydroxylase activity have a deficiency in metabolism of biopterin, possibly a diminution of dihydropterin reductase activity. We should like to emphasise that any condition which reduced the amount of active tetrahydropterin cofactor would be expected to result in a similar syndrome. This might occur in dihydropterin-reductase deficiency, in increased mitochondrial oxidation of reduced cofactor, or through additional mechanisms as yet unknown. University of Southern California, School of Medicine, 2025 Zonal Avenue, Los
Angeles, California 90033, U.S.A.
DORIS TAYLOR PAUL HOCHSTEIN.
INFANT FEEDS AND SOFTENED WATER
SIR,-It may well not be realised by the medical and nursing professions, let alone the public at large, how much the softening of water by the ion-exchange method increases the sodium content and thus raises dangerously the levels in infant feeds made up with such water. Dr Robertson (May 31, p. 1246) must be congratulated on drawing attention to this hazard. Water may be softened at source, in the hospital, or in the home, and there must be many babies subjected to the danger of solute loads even higher than that in feeds prepared with unsoftened water using the old-generation milks which still flood the market. It would be in the interest of all infants if those of us responsible for their feeds were to look into what is going on around us so that can be to rights. put
things
Smith, I. Archs Dis. Childh. 1974, 49, 245. Bartholome, K. Lancet, 1974, ii, 1580. Morrow, G. in Heritable Disorders of Amino Acid Metabolism (edited by W. Nyhan). New York, 1974. 4. Smith, I., Clayton, B., Wolff, O. Lancet, 1975, i, 328.
1. 2. 3.
We have discovered to our horror that feeds have been made up in the central milk kitchen of our maternity hospital for many years with softened water, and on estimating the Na, Ca, and P concentrations in milks made up with distilled water, ordinary mains water, and softened water, in this admittedly hard-water area, alarming discrepancies were shown. Na is increased by nearly 50 °o, and Ca is reduced by 15%, whereas P is little affected. We must admit to having seen a number of cases of neonatal tetany when an old-generation milk was made up with softened water, but the infants at this stage have caused us no concern over hypernatraemia, this obviously being a much bigger worry from the long-term point of view. Royal Infirmary, MAURICE G. PHILPOTT. Hull HU3 2JZ.
T AND B LYMPHOCYTES IN SPLEENS IN
HODGKIN’S DISEASE
SIR,-The paper of Dr Kaur and her associatesand subsequent correspondence 2,3 prompt us to make the following comment. Kaur1 found a significantly raised mean percentage of phytohaemagglutinin (P.H.A.)-responsive cells in the spleens of 10 patients with Hodgkin’s disease (67% transformed cells), compared with 28% in non-malignant spleens. No difference was found in the percentage of E-binding lymphocytes between the spleen and the peripheral blood, though the highest values of E-binding lymphocytes were recorded from the two heaviest spleens. Grifoni and his colleagues2 found an elevated percentage of E-binding lymphocytes in 1 of 5 spleens removed from Hodgkin’s patients. Joseph, Belpomme, and their colleagues 3,4 found in 8 histologically positive spleens of patients with Hodgkin’s disease a significantly higher percentage of E-binding lymphocytes than in 12 spleens without histological signs of the disease. We studied the P.H.A. stimulation test on peripheralblood lymphocytes in 17 Hodgkin’s patients before and 10 days after splenectomy. It was found that P.H.A. stimulation was not affected in Hodgkin’s patients with pathological stages I and II but was significantly (p < 0-005)
the
increased in those with stages III and IV.5 The relative proportions of T and B cells in the peripheral blood of 12 patients before and after splenectomy were measured by rosette formation. The proportion of E-binding lymphocytes was significantly diminished in 7 patients with spleens weighing 240 g. and more (P =0-001), whereas P.H.A.-stimulated thymidine incorporation increased significantly (P =0-015). The proportion of E.A.c.-binding lymphocytes also increased significantly in these patients (? =0-023). In the patients with a splenic weight less than 200 g. we did not find a significant difference after the operation. The decrease of E-binding lymphocytes in patients with resected spleens of more than 240 g. could be in accordance with the results of Belpomme and is possibly explained by the removal of an enlarged spleen containing more T lymphocytes than normal, thus the removal of many T cells. Although few cases were studied, the data suggest that the P.H.A. test does not run always parallel with the relative 1. 2.
3. 4.
5.
Kaur, J., Spiers, A. S. D., Catovsky, D., Galton, D. A. G. ibid. 1974, ii, 800. Grifoni, V., Del Giacco, G. S., Manconi, P. E., Tognella, S., Mantovani, G. ibid. 1975, i, 332. Joseph, R. R., Belpomme, D. ibid. p. 747. Belpomme, D., Joseph, R. R., Navares, L., Gerard-Marchant, R., Huchet, R., Botto, I., Grandjon, D., Mathé, G. New Engl. J. Med. 1974, 291, 1417. Wagener, D. J. Th., Geestman, E., Wessels, J. M. C. Cancer, N.Y. (in the press).
was
prescribed ? Nearly all therapeutic
agents have actions additional to that of lowering arterial pressure. (3) What was the evidence submitted to the patients that reducing arterial pressures of 95-100 mm. Hg diastolic, measured of course under similar circumstances, would reduce morbidity and mortality ?
Unless there is evidence of which I am ignorant, I am that I would be a non-complier, however convenient it was made for me to attend a physician. sure
The Grange, Moulsford-on-Thames, Berkshire OX10 9JD.
GEORGE PICKERING.
POTENTIAL VARIANTS OF PHENYLKETONURIA SIR,-The syndrome in which children have biochemical manifestations of phenylketonuria and additional neurological problems, but have normal liver phenylalanine hydroxylase activity,l.2 is arousing interest among those studying metabolic diseases. We are preparing data for publication which indicate that mitochondria have a potential role to play in the regulation of aromatic aminoacid hydroxylases. Addition of mitochondria to the soluble fraction of rat liver homogenate results in inhibition of phenylalanine-hydroxylase activity. This is possible even in the presence of adequate oxygen because mitochondria oxidise tetrahydropterins over cytochrome c and cytochrome oxidase, thereby diminishing the amount of active cofactor available for the hydroxylation reaction. It is clear from studies of other metabolic disorders-for example, methylmalonic aciduria 3-that different genetic mutations involving the apoenzyme or cofactor metabolism may result in a similar clinical picture. It has been postulated that P.K.U. patients with normal phenylalanine hydroxylase activity have a deficiency in metabolism of biopterin, possibly a diminution of dihydropterin reductase activity. We should like to emphasise that any condition which reduced the amount of active tetrahydropterin cofactor would be expected to result in a similar syndrome. This might occur in dihydropterin-reductase deficiency, in increased mitochondrial oxidation of reduced cofactor, or through additional mechanisms as yet unknown. University of Southern California, School of Medicine, 2025 Zonal Avenue, Los
Angeles, California 90033, U.S.A.
DORIS TAYLOR PAUL HOCHSTEIN.
INFANT FEEDS AND SOFTENED WATER
SIR,-It may well not be realised by the medical and nursing professions, let alone the public at large, how much the softening of water by the ion-exchange method increases the sodium content and thus raises dangerously the levels in infant feeds made up with such water. Dr Robertson (May 31, p. 1246) must be congratulated on drawing attention to this hazard. Water may be softened at source, in the hospital, or in the home, and there must be many babies subjected to the danger of solute loads even higher than that in feeds prepared with unsoftened water using the old-generation milks which still flood the market. It would be in the interest of all infants if those of us responsible for their feeds were to look into what is going on around us so that can be to rights. put
things
Smith, I. Archs Dis. Childh. 1974, 49, 245. Bartholome, K. Lancet, 1974, ii, 1580. Morrow, G. in Heritable Disorders of Amino Acid Metabolism (edited by W. Nyhan). New York, 1974. 4. Smith, I., Clayton, B., Wolff, O. Lancet, 1975, i, 328.
1. 2. 3.
We have discovered to our horror that feeds have been made up in the central milk kitchen of our maternity hospital for many years with softened water, and on estimating the Na, Ca, and P concentrations in milks made up with distilled water, ordinary mains water, and softened water, in this admittedly hard-water area, alarming discrepancies were shown. Na is increased by nearly 50 °o, and Ca is reduced by 15%, whereas P is little affected. We must admit to having seen a number of cases of neonatal tetany when an old-generation milk was made up with softened water, but the infants at this stage have caused us no concern over hypernatraemia, this obviously being a much bigger worry from the long-term point of view. Royal Infirmary, MAURICE G. PHILPOTT. Hull HU3 2JZ.
T AND B LYMPHOCYTES IN SPLEENS IN
HODGKIN’S DISEASE
SIR,-The paper of Dr Kaur and her associatesand subsequent correspondence 2,3 prompt us to make the following comment. Kaur1 found a significantly raised mean percentage of phytohaemagglutinin (P.H.A.)-responsive cells in the spleens of 10 patients with Hodgkin’s disease (67% transformed cells), compared with 28% in non-malignant spleens. No difference was found in the percentage of E-binding lymphocytes between the spleen and the peripheral blood, though the highest values of E-binding lymphocytes were recorded from the two heaviest spleens. Grifoni and his colleagues2 found an elevated percentage of E-binding lymphocytes in 1 of 5 spleens removed from Hodgkin’s patients. Joseph, Belpomme, and their colleagues 3,4 found in 8 histologically positive spleens of patients with Hodgkin’s disease a significantly higher percentage of E-binding lymphocytes than in 12 spleens without histological signs of the disease. We studied the P.H.A. stimulation test on peripheralblood lymphocytes in 17 Hodgkin’s patients before and 10 days after splenectomy. It was found that P.H.A. stimulation was not affected in Hodgkin’s patients with pathological stages I and II but was significantly (p < 0-005)
the
increased in those with stages III and IV.5 The relative proportions of T and B cells in the peripheral blood of 12 patients before and after splenectomy were measured by rosette formation. The proportion of E-binding lymphocytes was significantly diminished in 7 patients with spleens weighing 240 g. and more (P =0-001), whereas P.H.A.-stimulated thymidine incorporation increased significantly (P =0-015). The proportion of E.A.c.-binding lymphocytes also increased significantly in these patients (? =0-023). In the patients with a splenic weight less than 200 g. we did not find a significant difference after the operation. The decrease of E-binding lymphocytes in patients with resected spleens of more than 240 g. could be in accordance with the results of Belpomme and is possibly explained by the removal of an enlarged spleen containing more T lymphocytes than normal, thus the removal of many T cells. Although few cases were studied, the data suggest that the P.H.A. test does not run always parallel with the relative 1. 2.
3. 4.
5.
Kaur, J., Spiers, A. S. D., Catovsky, D., Galton, D. A. G. ibid. 1974, ii, 800. Grifoni, V., Del Giacco, G. S., Manconi, P. E., Tognella, S., Mantovani, G. ibid. 1975, i, 332. Joseph, R. R., Belpomme, D. ibid. p. 747. Belpomme, D., Joseph, R. R., Navares, L., Gerard-Marchant, R., Huchet, R., Botto, I., Grandjon, D., Mathé, G. New Engl. J. Med. 1974, 291, 1417. Wagener, D. J. Th., Geestman, E., Wessels, J. M. C. Cancer, N.Y. (in the press).
