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MATERNAL LYMPHOCYTOTOXIC ANTIBODIES AND NEONATAL HYPERBILIRUBINÆMIA
564 in normal serum is being investigated. In the meantime it might be advisable, for clinical purposes, to have two sets of standards available for bioassay methods-one prepared in pooled normal sera and one in pooled urasmic sera. Another possibility would be to use an enzyme assay method such as that of Smith et al.4 who claimed that the accuracy of their assay was not affected when specimens with concentrations of blood-urea-nitrogen up to 80 mg. per 100 ml. were tested. Departments of Clinical Microbiology and Nephrological Service, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
J. STESSMAN J. MICHEL A. LIGHT T. SACKS.
MATERNAL LYMPHOCYTOTOXIC ANTIBODIES AND NEONATAL HYPERBILIRUBINÆMIA
SIR,-van Rood claimed5 that maternal leucocyte antibodies might be important in pregnancy or for the condition of the newborn child. Nevertheless, no clinically significant leucocyte fetomaternal immunisation has been found except for rare cases of alloimmune neonatal thrombocytopenia6 or neutropenia due to neutrophilspecific antibodies.’7 It used to be thought that HL-A antigens were absent on the surface of red blood-cells. However, there is now evidence that human leucocyte antigens are well expressed on erythrocytes 8 (mainly on reticulocytes and erythroblasts 9). This accounts for the shortened lifespan of , HL-A-incompatible reticulocytes when transfused into recipients with circulating cytotoxic antibodies.1O We wouldexpect lymphocytotoxins entering the fetal circulation to damage the younger red blood-cells and potentiate any haemolysis in the newborn. We have looked for cytotoxins 11 against the husband’s lymphocytes at delivery in 100 randomly selected pregnant women, most of whom were multigravid. Samples of cord blood were collected for direct antiglobulin tests and cytotoxicity tests against the father’s lymphocytes. Serumbilirubin levels were measured on the 4th and 7th days of life or more frequently when required for clinical purposes. Each case was monitored for ABO and Rh incompatibility, maternal or neonatal infections, and any other causes of neonatal jaundice, especially for G-6-P.D. deficiency which is quite common in this region. We found cytotoxic antibodies in 32 of the mothers. No antibodies were demonstrable in any of the cord bloods. 23 babies were hyperbilirubinasmic, their serum-bilirubins exceeding 10 mg. per 100 ml. by the 4th day of life for full-term infants, or 14 mg. per 100 ml. within 7 days for premature infants. No baby had severe jaundice that required exchange transfusion. The direct antiglobulin test was never positive, even in ABO and Rh incompatibilities. For 14 of the 23 hyperbilirubinxmic infants there were lymphocytotoxic antibodies in the mother while neonatal hyperbilirubinaemia was present in only 18 of the 77 infants without such antibodies (=11-4; p< 0-001). If all babies with a possible cause of neonatal jaundice are removed from the computation (13 ABO, 3 ABO+Rh, and 4 Rh incompati4.
Smith, D. H., Van Otto, R., Smith, A.
6.
Colombani, J., Colombani, Monique, Dausset, J. Vox sang. 1968, 14, 137. Walford, R. L. Ser. Hæmat. 1969, 2, 2. Doughty, R. W., Goodier, S. R., Gelsthorpe, K. Tissue Antigens, 1973, 3, 189. Harris, R., Zervas, J. D. Nature, 1969, 221, 1062. Zervas, J. D., Delamore, I. W., Cunliffe, D. J., Israels, M. C. G. Br. J. Hæmat. 1972, 23, 453. Terasaki, P. I., McClelland, J. D. Nature, 1964, 204, 998.
L. New Engl. J. Med. 1972, 286, 583. 5. van Rood, J. J., Eernisse, J. G., van Leeuwen, A. Nature, 1958, 181,
1735.
7. 8. 9. 10.
11.
cases of G-6-P.D. deficiency), the correlation persists (x2=58, P<0-02). These findings are consistent with a possible influence of
bilities and 4
maternal anti-HL-A antibodies on bilirubin levels of the newborn; but no direct evidence has been reached of any immune erythrocyte damage. HL-A antigens free in the serum 12 and widely represented on the surface of many tissue cells may capture maternal cytotoxins more avidly than do red blood-cells. This fact can justify the moderate haemolysis we observed, the negative direct antiglobulin test, and the absence of free antibody in the serum of the newborn. G. CARANDINA L. DERITIS E. MORETTO P. PALAZZI Ospedale " F. lli Borselli," F. RANDAZZO. 44012 Bondeno, Ferrara, Italy. HERPES SIMPLEX
SIR,-Your issue of June 14 contains an editorial (p. 1324) on the treatment of herpes simplex encephalitis and a Letter to the Editor (p. 1343) by Dr Kobza and others who had found local idoxuridine ineffective and intravenous cytosine arabinoside unduly toxic in an immunosuppressed patient with herpetic lesions. In 22 cases with herpesvirus lesions (labialis, genitalis, and keratitis) we have administered parentally adenine nucleotide 13 for herpes zoster and simplex infections, including 1 case of subacute viral meningoencephalitis, with relief from pain and discomfort within three to ten days. The herpetic lesions dried and became discrete within seventy-two hours, and this was followed by desquamation and healing of the involved skin. With residual neuralgia, recovery was commensurate with the duration of the neuritis, degree of neuronal involvement, and the onset of therapy. The drug gave a rare fleeting experience of light-headedness and weakness; but no toxic effects have been observed, even when it was administered for four years to a child who came under treatment at the age of 18 months.14 We find that adenine nucleotide possesses antiviral activity without the serious toxic effects of an antimetabolite. .
Englewood Hospital, Englewood, N.J., U.S.A.
S. HARVEY SKLAR.
RECURRENT HYPERTHYROIDISM AFTER IODINE-125 TREATMENT
SIR,-Persistent hyperthyroidism after treatment of Graves’ disease with iodine-131 is not uncommon. In some patients a rapid remission is seen after such treatment, followed by a relapse within a few months, but a true recurrence appears to be very rare. In a small therapeutic trial with another radioactive isotope, iodine- 125,15-17 2 (possibly 3) out of 12 patients were found to have a recurrence of their hyperthyroidism after having been clinically and biochemically euthyroid for about a year. All 3 patients were subsequently treated with iodine-131. Of the other 9 patients treated with iodine-125 in this series, 1 died of an unrelated cause while euthyroid after 30 months, another was treated with iodine-131 while still 12.
Rood, J. J., 1970, 226, 366.
van
van
Leeuwen, A.,
van
Santen, M. C. T. ibid.
13. Sklar, S. Hosp. Practice, 1975, 10, 17. 14. Sklar, S., Wigand, J.J. Am. med. Ass. 1973, 226, 1464. 15. Wiener, J. D. Lancet, 1970, i, 783. 16. Werner, S. C., Johnson, P. M., Goodwin, P. N., Wiener, J. D., Lindeboom, G. A. ibid. 1970, ii, 681. 17. Wiener, J. D. ibid. 1971, ii, 155.
J. STESSMAN J. MICHEL A. LIGHT T. SACKS.
MATERNAL LYMPHOCYTOTOXIC ANTIBODIES AND NEONATAL HYPERBILIRUBINÆMIA
SIR,-van Rood claimed5 that maternal leucocyte antibodies might be important in pregnancy or for the condition of the newborn child. Nevertheless, no clinically significant leucocyte fetomaternal immunisation has been found except for rare cases of alloimmune neonatal thrombocytopenia6 or neutropenia due to neutrophilspecific antibodies.’7 It used to be thought that HL-A antigens were absent on the surface of red blood-cells. However, there is now evidence that human leucocyte antigens are well expressed on erythrocytes 8 (mainly on reticulocytes and erythroblasts 9). This accounts for the shortened lifespan of , HL-A-incompatible reticulocytes when transfused into recipients with circulating cytotoxic antibodies.1O We wouldexpect lymphocytotoxins entering the fetal circulation to damage the younger red blood-cells and potentiate any haemolysis in the newborn. We have looked for cytotoxins 11 against the husband’s lymphocytes at delivery in 100 randomly selected pregnant women, most of whom were multigravid. Samples of cord blood were collected for direct antiglobulin tests and cytotoxicity tests against the father’s lymphocytes. Serumbilirubin levels were measured on the 4th and 7th days of life or more frequently when required for clinical purposes. Each case was monitored for ABO and Rh incompatibility, maternal or neonatal infections, and any other causes of neonatal jaundice, especially for G-6-P.D. deficiency which is quite common in this region. We found cytotoxic antibodies in 32 of the mothers. No antibodies were demonstrable in any of the cord bloods. 23 babies were hyperbilirubinasmic, their serum-bilirubins exceeding 10 mg. per 100 ml. by the 4th day of life for full-term infants, or 14 mg. per 100 ml. within 7 days for premature infants. No baby had severe jaundice that required exchange transfusion. The direct antiglobulin test was never positive, even in ABO and Rh incompatibilities. For 14 of the 23 hyperbilirubinxmic infants there were lymphocytotoxic antibodies in the mother while neonatal hyperbilirubinaemia was present in only 18 of the 77 infants without such antibodies (=11-4; p< 0-001). If all babies with a possible cause of neonatal jaundice are removed from the computation (13 ABO, 3 ABO+Rh, and 4 Rh incompati4.
Smith, D. H., Van Otto, R., Smith, A.
6.
Colombani, J., Colombani, Monique, Dausset, J. Vox sang. 1968, 14, 137. Walford, R. L. Ser. Hæmat. 1969, 2, 2. Doughty, R. W., Goodier, S. R., Gelsthorpe, K. Tissue Antigens, 1973, 3, 189. Harris, R., Zervas, J. D. Nature, 1969, 221, 1062. Zervas, J. D., Delamore, I. W., Cunliffe, D. J., Israels, M. C. G. Br. J. Hæmat. 1972, 23, 453. Terasaki, P. I., McClelland, J. D. Nature, 1964, 204, 998.
L. New Engl. J. Med. 1972, 286, 583. 5. van Rood, J. J., Eernisse, J. G., van Leeuwen, A. Nature, 1958, 181,
1735.
7. 8. 9. 10.
11.
cases of G-6-P.D. deficiency), the correlation persists (x2=58, P<0-02). These findings are consistent with a possible influence of
bilities and 4
maternal anti-HL-A antibodies on bilirubin levels of the newborn; but no direct evidence has been reached of any immune erythrocyte damage. HL-A antigens free in the serum 12 and widely represented on the surface of many tissue cells may capture maternal cytotoxins more avidly than do red blood-cells. This fact can justify the moderate haemolysis we observed, the negative direct antiglobulin test, and the absence of free antibody in the serum of the newborn. G. CARANDINA L. DERITIS E. MORETTO P. PALAZZI Ospedale " F. lli Borselli," F. RANDAZZO. 44012 Bondeno, Ferrara, Italy. HERPES SIMPLEX
SIR,-Your issue of June 14 contains an editorial (p. 1324) on the treatment of herpes simplex encephalitis and a Letter to the Editor (p. 1343) by Dr Kobza and others who had found local idoxuridine ineffective and intravenous cytosine arabinoside unduly toxic in an immunosuppressed patient with herpetic lesions. In 22 cases with herpesvirus lesions (labialis, genitalis, and keratitis) we have administered parentally adenine nucleotide 13 for herpes zoster and simplex infections, including 1 case of subacute viral meningoencephalitis, with relief from pain and discomfort within three to ten days. The herpetic lesions dried and became discrete within seventy-two hours, and this was followed by desquamation and healing of the involved skin. With residual neuralgia, recovery was commensurate with the duration of the neuritis, degree of neuronal involvement, and the onset of therapy. The drug gave a rare fleeting experience of light-headedness and weakness; but no toxic effects have been observed, even when it was administered for four years to a child who came under treatment at the age of 18 months.14 We find that adenine nucleotide possesses antiviral activity without the serious toxic effects of an antimetabolite. .
Englewood Hospital, Englewood, N.J., U.S.A.
S. HARVEY SKLAR.
RECURRENT HYPERTHYROIDISM AFTER IODINE-125 TREATMENT
SIR,-Persistent hyperthyroidism after treatment of Graves’ disease with iodine-131 is not uncommon. In some patients a rapid remission is seen after such treatment, followed by a relapse within a few months, but a true recurrence appears to be very rare. In a small therapeutic trial with another radioactive isotope, iodine- 125,15-17 2 (possibly 3) out of 12 patients were found to have a recurrence of their hyperthyroidism after having been clinically and biochemically euthyroid for about a year. All 3 patients were subsequently treated with iodine-131. Of the other 9 patients treated with iodine-125 in this series, 1 died of an unrelated cause while euthyroid after 30 months, another was treated with iodine-131 while still 12.
Rood, J. J., 1970, 226, 366.
van
van
Leeuwen, A.,
van
Santen, M. C. T. ibid.
13. Sklar, S. Hosp. Practice, 1975, 10, 17. 14. Sklar, S., Wigand, J.J. Am. med. Ass. 1973, 226, 1464. 15. Wiener, J. D. Lancet, 1970, i, 783. 16. Werner, S. C., Johnson, P. M., Goodwin, P. N., Wiener, J. D., Lindeboom, G. A. ibid. 1970, ii, 681. 17. Wiener, J. D. ibid. 1971, ii, 155.