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SPHINGOMYELIN RATIOS AND DEXAMETHASONE
575 obtain release from the Committee on Safety of Medicines. Therefore, little was known about cephradine in the United Kingdom before its general release. Your comment appears quite rightly to place a degree of importance on clinical trials since this provides objective evidence. It is surprising, therefore, that some of your remarks seem to be based on subjective impressions only. to
G. R. DANIEL, Medical Director. E. R.
Squibb and Sons Limited, Regal House,
Twickenham TW1 3QT.
T. K.
CLARKE,
Associate Medical Director.
AMNIOTIC-FLUID LECITHIN/SPHINGOMYELIN RATIOS AND DEXAMETHASONE
SiR,—The lecithin/sphingomyelin (L/S) ratio in the amniotic fluid seems to be of considerable clinical significance in predicting respiratory maturity and neonatal outcome. 1-4 However, the problem of managing pregnancies complicated by unplanned or planned prematurity remains. An attempt to induce intrauterine lung maturation by glucocorticoids was reported by Liggins and Howie 6; the incidence of respiratory-distress syndrome in premature babies only fell when glucocorticoids had been given at least 48 hours before delivery. Spellacy et al. showed that glucocorticoid administration in pregnant women produces a significantly greater rate in rise of the L/S ratio in amniotic fluid, estimated on two occasions 2 weeks apart, than in control or in oestrogen-treated groups. However, the exact interval between the administration of glucocorticosteroids and the rise of the L/S ratio is as yet unknown. We have measured, almost daily, the L/S ratio in the amniotic fluid carefully collected from a patient admitted 1.
2. 3. 4. 5. 6.
Gluck, L., Kulovich, M. V., Borer, R. C., Brenner, P. H., Anderson, G. G., Spellacy, W. N. Am. J. Obstet. Gynec. 1971, 109, 440. Gerbie, M. V., Gerbie, A. B., Boehm, J. ibid. 1972, 114, 1078. Gluck, L., Kulovich, M. V. ibid. 1973, 115, 539. Donald, I. R., Freeman, R. K., Goebelsmann, U., Chan, W. H., Nakamura, R. M. ibid. p. 547. Liggins, G. C., Howie, R. N. Pediatrics, 1972, 50, 515. Spellacy, W. N., Buhi, W. C., Rigall, F. C., Holsinger, K. L. Am. J. Obstet. Gynec. 1973, 115, 216.
with premature rupture of the membranes at the 33rd week of pregnancy. Lipids were extracted, and surface-active lecithin was precipitated in cold acetone,l spotted on silica gel G, developed in chloroform/methanol/water (80/35/5), visualised by saturation with iodine and phosphorus, and determined by Bartlett’s method.7 The baseline L/S ratio was established and then 4 mg. dexamethasone was given by mouth daily for 8 days. After 3 days, the L/S ratio rose sharply. This trend continued on further treatment. The rate of rise of the L/S ratio was greater than that seen in normal or diabetic patients who had received no steroid treatment (see figure). After 8 days of treatment, labour was induced by intravenous oxytocin infusion. A male weighing 2700 g. with an Apgar score 10 was delivered. The baby did not require incubator care. This observation seems to confirm the clinical findings of Liggins and Howie5 that relatively brief intrauterine exposure of human infants to dexamethasone induces lung maturation, reflected in higher surfactant release into amniotic fluid. It seems that, in planned and unplanned premature deliveries, delivery should be delayed for at least 48 hours, so that the steroids given to the mother may have a chance to reduce the risk of respiratory distress. Department of Obstetrics and Gynæcology, Asaf Harofe Government Hospital, University of Tel-Aviv, Zerifin.
Metabolic Unit, Hadassa Hospital, University of Tel-Aviv, Tel-Aviv, Israel.
E. CASPI P. SCHREYER.
I. TAMIR.
CHEMICAL RADIOPROTECTION OF RADIOLOGISTS SiR,—There is evidence that in radiologists the principal radiochemical injuries by chronic ionising radiations are chromosomal and D.N.A. breaks. The protective ability of various compounds has been demonstrated on microorganisms, vegetables, and human animal cells in vitro. 8-10 In irradiated mammals, effective radioprotection was attained by administration of nucleic acids.llI- Also, the administration of D.N.A. increased the survival-rate of mice radiosensitive strain BALB/c+.12 Lymphocyte metaphases of eight radiologists chronically exposed to X rays were analysed, and the frequency of chromosome abnormalities was calculated at four different times. After 48 hours’ incubation (first cell division), 100 cells by culture were classified. During the study three radiologists were treated with calf-thymus highly polymerised D.N.A. (5 mg. per kg. per day) and A.T.P. (0-5 mg. per kg. per day) (see accompanying Three unexposed controls (100 mitoses per figure). or
culture)
were
simultaneously analysed.
The results indicate that radioprotection was attained when the radiologists were treated with D.N.A. and A.T.P. (100% decrease in the rate of cells with structural chromosome aberrations). When the treatment was suspended, the chromosome abnormalities rose again (see figure). A percentage decrease of numerical chromosome aberrations was noted in a treated radiologist. However, 7. 8.
L/S ratios showing steep rise in patient given dexamethasone (-) compared with eleven patients not given the drug (——). The final ratio in each case is the one at delivery.
Bartlett, G. R. J. biol. Chem. 1959, 234, 466. Leon, S., Kollmann, G., Shapiro, B. Int. J. Radiat. Biol. 1971, 20,
337. 9. Mikaelsen, K., Pedersen, K. Hereditas, 1968, 60, 399. 10. Roots, R., Okada, S. Int. J. Radiat. Biol. 1972, 21, 329. 11. Wilczok, T., Mendecki, J. ibid. 1965, 9, 201. 12. Charles, P., Ledoux, L., Maisin, J., Mattelin, G., Remy, int. Physiol. Biochim. 1971, 79, 822.
J. Arch.
G. R. DANIEL, Medical Director. E. R.
Squibb and Sons Limited, Regal House,
Twickenham TW1 3QT.
T. K.
CLARKE,
Associate Medical Director.
AMNIOTIC-FLUID LECITHIN/SPHINGOMYELIN RATIOS AND DEXAMETHASONE
SiR,—The lecithin/sphingomyelin (L/S) ratio in the amniotic fluid seems to be of considerable clinical significance in predicting respiratory maturity and neonatal outcome. 1-4 However, the problem of managing pregnancies complicated by unplanned or planned prematurity remains. An attempt to induce intrauterine lung maturation by glucocorticoids was reported by Liggins and Howie 6; the incidence of respiratory-distress syndrome in premature babies only fell when glucocorticoids had been given at least 48 hours before delivery. Spellacy et al. showed that glucocorticoid administration in pregnant women produces a significantly greater rate in rise of the L/S ratio in amniotic fluid, estimated on two occasions 2 weeks apart, than in control or in oestrogen-treated groups. However, the exact interval between the administration of glucocorticosteroids and the rise of the L/S ratio is as yet unknown. We have measured, almost daily, the L/S ratio in the amniotic fluid carefully collected from a patient admitted 1.
2. 3. 4. 5. 6.
Gluck, L., Kulovich, M. V., Borer, R. C., Brenner, P. H., Anderson, G. G., Spellacy, W. N. Am. J. Obstet. Gynec. 1971, 109, 440. Gerbie, M. V., Gerbie, A. B., Boehm, J. ibid. 1972, 114, 1078. Gluck, L., Kulovich, M. V. ibid. 1973, 115, 539. Donald, I. R., Freeman, R. K., Goebelsmann, U., Chan, W. H., Nakamura, R. M. ibid. p. 547. Liggins, G. C., Howie, R. N. Pediatrics, 1972, 50, 515. Spellacy, W. N., Buhi, W. C., Rigall, F. C., Holsinger, K. L. Am. J. Obstet. Gynec. 1973, 115, 216.
with premature rupture of the membranes at the 33rd week of pregnancy. Lipids were extracted, and surface-active lecithin was precipitated in cold acetone,l spotted on silica gel G, developed in chloroform/methanol/water (80/35/5), visualised by saturation with iodine and phosphorus, and determined by Bartlett’s method.7 The baseline L/S ratio was established and then 4 mg. dexamethasone was given by mouth daily for 8 days. After 3 days, the L/S ratio rose sharply. This trend continued on further treatment. The rate of rise of the L/S ratio was greater than that seen in normal or diabetic patients who had received no steroid treatment (see figure). After 8 days of treatment, labour was induced by intravenous oxytocin infusion. A male weighing 2700 g. with an Apgar score 10 was delivered. The baby did not require incubator care. This observation seems to confirm the clinical findings of Liggins and Howie5 that relatively brief intrauterine exposure of human infants to dexamethasone induces lung maturation, reflected in higher surfactant release into amniotic fluid. It seems that, in planned and unplanned premature deliveries, delivery should be delayed for at least 48 hours, so that the steroids given to the mother may have a chance to reduce the risk of respiratory distress. Department of Obstetrics and Gynæcology, Asaf Harofe Government Hospital, University of Tel-Aviv, Zerifin.
Metabolic Unit, Hadassa Hospital, University of Tel-Aviv, Tel-Aviv, Israel.
E. CASPI P. SCHREYER.
I. TAMIR.
CHEMICAL RADIOPROTECTION OF RADIOLOGISTS SiR,—There is evidence that in radiologists the principal radiochemical injuries by chronic ionising radiations are chromosomal and D.N.A. breaks. The protective ability of various compounds has been demonstrated on microorganisms, vegetables, and human animal cells in vitro. 8-10 In irradiated mammals, effective radioprotection was attained by administration of nucleic acids.llI- Also, the administration of D.N.A. increased the survival-rate of mice radiosensitive strain BALB/c+.12 Lymphocyte metaphases of eight radiologists chronically exposed to X rays were analysed, and the frequency of chromosome abnormalities was calculated at four different times. After 48 hours’ incubation (first cell division), 100 cells by culture were classified. During the study three radiologists were treated with calf-thymus highly polymerised D.N.A. (5 mg. per kg. per day) and A.T.P. (0-5 mg. per kg. per day) (see accompanying Three unexposed controls (100 mitoses per figure). or
culture)
were
simultaneously analysed.
The results indicate that radioprotection was attained when the radiologists were treated with D.N.A. and A.T.P. (100% decrease in the rate of cells with structural chromosome aberrations). When the treatment was suspended, the chromosome abnormalities rose again (see figure). A percentage decrease of numerical chromosome aberrations was noted in a treated radiologist. However, 7. 8.
L/S ratios showing steep rise in patient given dexamethasone (-) compared with eleven patients not given the drug (——). The final ratio in each case is the one at delivery.
Bartlett, G. R. J. biol. Chem. 1959, 234, 466. Leon, S., Kollmann, G., Shapiro, B. Int. J. Radiat. Biol. 1971, 20,
337. 9. Mikaelsen, K., Pedersen, K. Hereditas, 1968, 60, 399. 10. Roots, R., Okada, S. Int. J. Radiat. Biol. 1972, 21, 329. 11. Wilczok, T., Mendecki, J. ibid. 1965, 9, 201. 12. Charles, P., Ledoux, L., Maisin, J., Mattelin, G., Remy, int. Physiol. Biochim. 1971, 79, 822.
J. Arch.