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GENTAMICIN AND BILIRUBIN-BINDING BY PLASMA
1195
plus 0-025 ml. pooled serum, using a microtitre dropper. Otherwise the test procedure remains as described for adults. The total volume of serum required here is 0.375 ml., and in this and all modifications further economy of serum can be achieved without loss of accuracy by omitting the tubes containing the lowest concentration of gentamicin standard. serum
We thus describe a basic assay for adults with two modifications to fulfil the requirements of any particular department according to their proportion of pxdiatric work or the necessity to measure low concentrations accurately. Department of Bacteriology, School of Pathology, Middlesex Hospital Medical School, Riding House Street, London W1P 7LD.
PAUL NOONE
J. R. PATTISON R. C. B. SLACK.
GENTAMICIN AND BILIRUBIN-BINDING BY PLASMA
SiR,-Gentamicin is becoming the therapy of choice in the treatment of neonatal sepsis.l Recently Sternreported that gentamicin added in vitro to bilirubin-albumin solutions uncouples bilirubin from its bond to albumin. If this also occurs in vivo, gentamicin may not be a desirable drug to use in jaundiced neonates, especially premature infants, in whom both sepsis and jaundice are more common. We therefore estimated the bilirubin-binding capacity of the plasma of a jaundiced infant with sepsis who was treated with gentamicin. A 2000-g. Caucasian baby delivered by caesarean section developed signs of sepsis on the second day of life. Along with other clinical signs of sepsis he developed jaundice as well. He was treated with gentamicin, 2 mg. per kg. intramuscularly every 12 hours. Blood samples were drawn and collected in heparinised tubes, before and four hours after the first injection. EFFECT OF GENTAMICIN ON BILIRUBIN-BINDING
* Plasma with no addition of bilirubin. To all other specimens bilirubin was added in increasing amounts and final concentrations determined. Albumin concentration: 3-7 g./100 ml.
separated by centrifugation, and total bilirubin,S and albumin bilirubin-binding capacity by a ’Sephadex’gel filtration method 5 were determined on each sample. Bilirubin was then added to the plasma in increments of about 2’5 mg. per 100 ml. and the sephadex test repeated. Free bilirubin adsorbed on the sephadex column was demonstrated by a diazo reagent Plasma
was
(’ Ictotest’). Before gentamicin
was administered the plasma-bilirubin 12-1 mg. per 100 ml. and the sephadex test was negative (see accompanying table). When the bilirubin concentration was artificially raised to 19-2 mg. per 100 ml., free bilirubin appeared and was adsorbed by the column. After
concentration
was
the infant was injected with gentamicin the plasma-bilirubin concentration was found to be 14mg. per 100 ml. and the sephadex test was negative, but became positive after the bilirubin 1. 2. 3. 4. 5.
Nelson, J. D., McCracken, G. H., Jr. Am. J. Dis. Child. 1972, 124, 13. Stern, L. Pediatrics, 1972, 49, 916. Malloy, H. T., Evelyn, K. A. J. biol. Chem. 1937, 119, 481. Fernandez, A., Sobel, C., Goldenberg, H. Clin. Chem. 1966, 12, 194. Blondheim, S. H., Kapitulnik, J., Valaes, T., Kaufmann, N. A. Isr. J. med. Sci. 1972, 8, 22.
concentration was artificially increased to a lower concentration than before-17-5 mg. per 100 ml. Moreover, at bilirubin concentrations higher than 21 mg. per 100 ml. more bilirubin was adsorbed from plasma obtained after injection of gentamicin than from that obtained before, at approximately equal bilirubin concentrations (see table).
It thus
seems
that
gentamicin, when injected into infants,
interferes with the binding of bilirubin by plasma-albumin, as demonstrated by the adsorption of bilirubin on sephadex at lower plasma-bilirubin concentrations than in the absence of the drug. This effect of gentamicin when injected into infants with sepsis and jaundice may increase the danger of bilirubin encephalopathy and seems to be similar to that of sulphonamides, which can produce kernicterus in jaundiced infants.6 Gentamicin should therefore be used with caution in jaundiced infants, especially prematures, and if possible the plasma bilirubin-binding capacity should be monitored. Metabolic Laboratory and
Departments of Medicine B and Pediatrics, Hadassah-University Hospital and Hebrew University-Hadassah Medical School,
Jerusalem,
Israel.
J. KAPITULNIK F. EYAL A. J. SIMCHA.
SYNTHETIC FOODS
SIR,-Your editorial (Nov. 11, p. 1012) was extremely interesting. While we agree with practically all the points you make, there are certain aspects which need further comment. You quote the 1969 food survey as showing an " average at-home protein consumption of 74 g. per person per day (193% of minimum requirement) ". At present this is certainly true, but it is possible such a situation could change, and there would be a scarcity of meat products. It is true in this situation that one could rely on wheat and other grains to supply the dietary protein, but this would be extremely monotonous. You say the high technology required for further production makes it most unlikely that developing countries will ever be able to afford it. This seems unlikely, since, for example, several developing countries are producing large quantities of soya milk; if such countries do not have the technology required to produce these protein foods then these products can be imported from countries which are producing them. There have been available for over twenty years concentrated vegetable protein made mainly from soya and sometimes with the addition of gluten. The composition of these foods has been analysed by Miller and Mumford.7 Such protein foods have been the main source of protein for many vegans in this country. Extensive research on these individuals has shown them to be as healthy as omnivores. 8-10 These particular plant-protein foods were looked on, and rightly so, with certain criticisms by nutritionists and the lay public. However, they have proved to be adequate nutrients and showed no harmful effects. Processed plant protein releases a vast amount of land for further food production-for example, if plant food is processed through an animal as much as 90% is wasted, so it is obvious that more plant food will have to be utilised directly, and animal husbandry will have to be diminished as the world population grows. As this growth at present is proceeding at a fantastic rate, it is obvious the production of more plant foods is urgent. 6. 7. 8.
Silverman, W. A., Andersen, D. H., Blanc, W. A., Crozier, D. N. Pediatrics, 1956, 18, 614. Miller, D. S., Mumford, P. Pl. Fds hum. Nutr. 1972, 2, 201. Ellis, F. R., Montegriffo, V. M. E. Am. J. clin. Nutr. 1970, 123,
249. 9. West, E. D. Pl. Fds hum. Nutr. 1971, 2, 147. 10. Kurtha, A. N., Ellis, F. R. ibid. p. 53.
plus 0-025 ml. pooled serum, using a microtitre dropper. Otherwise the test procedure remains as described for adults. The total volume of serum required here is 0.375 ml., and in this and all modifications further economy of serum can be achieved without loss of accuracy by omitting the tubes containing the lowest concentration of gentamicin standard. serum
We thus describe a basic assay for adults with two modifications to fulfil the requirements of any particular department according to their proportion of pxdiatric work or the necessity to measure low concentrations accurately. Department of Bacteriology, School of Pathology, Middlesex Hospital Medical School, Riding House Street, London W1P 7LD.
PAUL NOONE
J. R. PATTISON R. C. B. SLACK.
GENTAMICIN AND BILIRUBIN-BINDING BY PLASMA
SiR,-Gentamicin is becoming the therapy of choice in the treatment of neonatal sepsis.l Recently Sternreported that gentamicin added in vitro to bilirubin-albumin solutions uncouples bilirubin from its bond to albumin. If this also occurs in vivo, gentamicin may not be a desirable drug to use in jaundiced neonates, especially premature infants, in whom both sepsis and jaundice are more common. We therefore estimated the bilirubin-binding capacity of the plasma of a jaundiced infant with sepsis who was treated with gentamicin. A 2000-g. Caucasian baby delivered by caesarean section developed signs of sepsis on the second day of life. Along with other clinical signs of sepsis he developed jaundice as well. He was treated with gentamicin, 2 mg. per kg. intramuscularly every 12 hours. Blood samples were drawn and collected in heparinised tubes, before and four hours after the first injection. EFFECT OF GENTAMICIN ON BILIRUBIN-BINDING
* Plasma with no addition of bilirubin. To all other specimens bilirubin was added in increasing amounts and final concentrations determined. Albumin concentration: 3-7 g./100 ml.
separated by centrifugation, and total bilirubin,S and albumin bilirubin-binding capacity by a ’Sephadex’gel filtration method 5 were determined on each sample. Bilirubin was then added to the plasma in increments of about 2’5 mg. per 100 ml. and the sephadex test repeated. Free bilirubin adsorbed on the sephadex column was demonstrated by a diazo reagent Plasma
was
(’ Ictotest’). Before gentamicin
was administered the plasma-bilirubin 12-1 mg. per 100 ml. and the sephadex test was negative (see accompanying table). When the bilirubin concentration was artificially raised to 19-2 mg. per 100 ml., free bilirubin appeared and was adsorbed by the column. After
concentration
was
the infant was injected with gentamicin the plasma-bilirubin concentration was found to be 14mg. per 100 ml. and the sephadex test was negative, but became positive after the bilirubin 1. 2. 3. 4. 5.
Nelson, J. D., McCracken, G. H., Jr. Am. J. Dis. Child. 1972, 124, 13. Stern, L. Pediatrics, 1972, 49, 916. Malloy, H. T., Evelyn, K. A. J. biol. Chem. 1937, 119, 481. Fernandez, A., Sobel, C., Goldenberg, H. Clin. Chem. 1966, 12, 194. Blondheim, S. H., Kapitulnik, J., Valaes, T., Kaufmann, N. A. Isr. J. med. Sci. 1972, 8, 22.
concentration was artificially increased to a lower concentration than before-17-5 mg. per 100 ml. Moreover, at bilirubin concentrations higher than 21 mg. per 100 ml. more bilirubin was adsorbed from plasma obtained after injection of gentamicin than from that obtained before, at approximately equal bilirubin concentrations (see table).
It thus
seems
that
gentamicin, when injected into infants,
interferes with the binding of bilirubin by plasma-albumin, as demonstrated by the adsorption of bilirubin on sephadex at lower plasma-bilirubin concentrations than in the absence of the drug. This effect of gentamicin when injected into infants with sepsis and jaundice may increase the danger of bilirubin encephalopathy and seems to be similar to that of sulphonamides, which can produce kernicterus in jaundiced infants.6 Gentamicin should therefore be used with caution in jaundiced infants, especially prematures, and if possible the plasma bilirubin-binding capacity should be monitored. Metabolic Laboratory and
Departments of Medicine B and Pediatrics, Hadassah-University Hospital and Hebrew University-Hadassah Medical School,
Jerusalem,
Israel.
J. KAPITULNIK F. EYAL A. J. SIMCHA.
SYNTHETIC FOODS
SIR,-Your editorial (Nov. 11, p. 1012) was extremely interesting. While we agree with practically all the points you make, there are certain aspects which need further comment. You quote the 1969 food survey as showing an " average at-home protein consumption of 74 g. per person per day (193% of minimum requirement) ". At present this is certainly true, but it is possible such a situation could change, and there would be a scarcity of meat products. It is true in this situation that one could rely on wheat and other grains to supply the dietary protein, but this would be extremely monotonous. You say the high technology required for further production makes it most unlikely that developing countries will ever be able to afford it. This seems unlikely, since, for example, several developing countries are producing large quantities of soya milk; if such countries do not have the technology required to produce these protein foods then these products can be imported from countries which are producing them. There have been available for over twenty years concentrated vegetable protein made mainly from soya and sometimes with the addition of gluten. The composition of these foods has been analysed by Miller and Mumford.7 Such protein foods have been the main source of protein for many vegans in this country. Extensive research on these individuals has shown them to be as healthy as omnivores. 8-10 These particular plant-protein foods were looked on, and rightly so, with certain criticisms by nutritionists and the lay public. However, they have proved to be adequate nutrients and showed no harmful effects. Processed plant protein releases a vast amount of land for further food production-for example, if plant food is processed through an animal as much as 90% is wasted, so it is obvious that more plant food will have to be utilised directly, and animal husbandry will have to be diminished as the world population grows. As this growth at present is proceeding at a fantastic rate, it is obvious the production of more plant foods is urgent. 6. 7. 8.
Silverman, W. A., Andersen, D. H., Blanc, W. A., Crozier, D. N. Pediatrics, 1956, 18, 614. Miller, D. S., Mumford, P. Pl. Fds hum. Nutr. 1972, 2, 201. Ellis, F. R., Montegriffo, V. M. E. Am. J. clin. Nutr. 1970, 123,
249. 9. West, E. D. Pl. Fds hum. Nutr. 1971, 2, 147. 10. Kurtha, A. N., Ellis, F. R. ibid. p. 53.