606
Saene HKF, Stoutnebeek CP, Miranda DR, Zandstra DF, Langrehr D. Recent advances in the control of infection in patients with thoracic injury. Injury 1986; 17: 332-35. 3. Tetteroo GWM, Wagenvoort JHT, Castelein A, Tilanus HW, Ince C, Bruining HA. Selective decontamination to reduce gram negative colonisation and infections after oesophageal resection. Lancet 1990; 335: 704-07.
2.
van
Effect of inhaled corticosteroids on EBV-specific cytotoxic T cells and EBV oropharyngeal excretion SIR,-Inhaled corticosteroids are effective in chronic asthma, although the recommended doses can affect the hypothalamicpituitary-adrenal axis (HPA).l-8 We have studied 5 asthmatics who had used inhaled corticosteroids 300 g per day for more than 12 months, 14 other asthmatics treated differently, 5 control children in good health, and 10 nephrotic patients who were being treated with systemic glucocorticosteroids 0-5-1 mg/kg daily to evaluate the immunological effects of inhaled corticosteroids. All subjects were seropositive for Epstein-Barr virus (EBV). We examined oropharyngeal EBV excretion and the EBV-specific cytotoxic T-cell activity in peripheral blood. Umbilicalmononuclear cells converted into cell lines after exposure to the throat washings were examined for expression of EBV-specific nuclear antigens by anticomplement immunofluorescence.4,s Cellmediated immunity to EBV was assessed by T-cell-mediated regression of proliferating foci of exogenously infected autologous B cells.6 The data were expressed as a minimum number of originally seeded peripheral blood mononuclear cells required for 50%
regression (Reg)7 Positive cultures for oropharyngeal EBV were found in 84% of asthmatics using inhaled corticosteroids, 43% of asthmatics not on inhaled corticosteroids, 43% of controls, and 67% of the nephrotic patients (table). By contrast, EBV-specific cytotoxic T-cell activity was significantly decreased in nephrotic patients. The activity in patients who were on inhaled corticosteroids was slightly impaired, but the difference from that of healthy children was not significant. FREQUENCY OF TRANSFORMING EBV IN OROPHARYNGEAL EXCRETION AND EBV-SPECIFIC CYTOTOXIC T CELLS
Inhaled corticosteroids can adversely affect growth8 and bone formation9 in asthmatic patients. However, on strictly immunological or virological grounds, we believe that the results confirm that inhaled corticosteroids have the same degree of topical effects as, but fewer systemic effects than, systemic steroids. Oropharnygeal excretion of EBV did not correlate with the degree of impairment of T-cell immunity. Inhaled corticosteroids may act directly on pharnygeal cells that carry the agent in a latent state and may thus cause the virus to be reactivated.10 Department of Paediatrics, Nishi-Sapporo National Hospital, Sapporo, Japan; Department of Virology, Cancer Institute, Hokkaido University School of Medicine, and Department of Paediatrics, Sapporo Medical College, Sapporo
W. ABO S. IMAI M. SUGIURA N. TERAI T. OSATO Y. SHIMANO S. CHIBA
1. Tabachnik E, Zadik Z. Diurnal cortisol secretion dunng therapy with inhaled beclomethasone dipropionate in children with asthma. J Pediart 1991; 118: 294-97. 2 Vas R, Senior B, Morris M, Binkiewiz A. Adrenal effects of beclomethasone inhalation therapy in asthmatic children. J Pediatr 1982; 100: 660-62. 3. Wyatt R, Waschek J, Weinberger M, Sherman B. Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma. N Engl J Med 1978; 299: 1387-92. 4. Strauch B, Andrews LL, Siegel N, Miller G. Oropharyngeal excretion of Epstein-Barr virus by renal transplant recipients and other patients with immunosuppressive drugs. Lancet 1974; i: 234-37.
5. Reedman BM, Klein G. Cellular localization of an Epstein Barr virus (EBV) -associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines Int J Cancer 1973; 11: 499-520. 6. Moss DJ, Rickinson AB, Pope JH. Longterm T cell mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus induced transformation in cultures of seropositive donor leukocytes. Int J Cancer 1978; 22: 662-68. 7. Rickinson AB, Crawford D, Epstein MA. Inhibition of the in vitro outgrowth of Epstem-Barr virus-transformed lymphocytes by thymus-dependent lymphocytes from infectious mononucleosis patients. Clin Exp Immunol 1977; 28: 72-79 8. Wales JKH, Barnes ND, Swift PGF. Growth retardation in children on steroids for asthma. Lancet 1991, 338: 1535. 9. Teelucksingh S. Padfield PL, Tibi L, Gough KJ, Holt PR. Inhaled corticosteroids, bone formation, and osteocalcin. Lancet 1991; 338: 60-61. 10. Bauer G. Induction of Epstein-Barr virus early antigens by corticosteroids: inhibition by TPA and retinoic acid. Int J Cancer 1983; 31: 291-95.
In-utero fetal therapy with immunoglobulin for alloimmune thrombocytopenia SiR,—In up to half the cases of alloimmune thrombocytopenia and cerebral haemorrhage, the haemorrhage occurs in utero.’ Preventive measures include early delivery by caesarean section, treatment of the mother with high-dose immunoglobulin and steroids, and weekly fetal platelet transfusion.2 Because intracranial haemorrhages can occur before week 20, early caesarean section is of limited benefit. The effect of steroids on the fetus is unclear. Fetal platelet transfusion should be reserved for high-risk cases and maternal IgG therapy is not only expensive but also of disputed efficacy.3 No reported cases show a rise in platelet count to more than 100 x 109/1.4,5 We report successful administration of immunoglobulin into the umbilical cord by cordocentesis. The first child of a 31-year-old mother, who was negative for the platelet alloantigen P1A1, had a neonatal cerebral haemorrhage associated with thrombocytopenia (minimum 10x 109/1). plalspecific antibodies were detected in the maternal serum; the husband was homozygous for P1A1 (Prof C. Muller-Eckhard, Institute for Transfusion Medicine, Giessen, Germany). In week 24 of the second pregnancy, cordocentesis showed a platelet count of 127 x 109/1; re-sampling in week 33 showed a fall to 51 x 109/1 despite consistently low antibody titres. With the mother’s informed consent, IgG (Endobulin, Immuno) was administered to the fetus, bringing the IgG concentration from 42 to 14-1 gfl (maternal concentration 124). Further cordocentesis in week 35 showed that the platelet count had risen to 130 x 109/1. IgG was 10g/1 and a further 0-5 g immunoglobulin was administered. A final cordocentesis was done at 37 weeks after collecting maternal platelets for fetal platelet transfusion. The transfusion was stopped when platelets reached 173 x 109/1. A healthy baby was delivered by caesarean section. The cord blood had 201 x 109/1 platelets and 11 ’9 g/1 IgG. Cranial ultrasound revealed no cerebral haemorrhage. Until day 8 the platelet count remained over 100 x 109/1. This case supports our hypothesis that, as in the postnatal situationdirect fetal administration of IgG produces a sustained increase in platelet count in alloimmune thrombocytopenia if higher IgG concentrations are achieved in the fetus than in the mother. Because of the long half-life of IgG, treatment intervals can be longer than those with platelet transfusions. The procedure not only carries a lower risk but costs are also acceptable. Department of Obstetrics, University Hospital,
R. ZIMMERMANN
8091 Zurich, Switzerland
A. HUCH
Jumbelic MI, Ancona RJ, Kickler TS. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8: 312-17 2. Bussel J, McFarland J. Recommendations for the evaluation and treatment of neonatal autoimmune and alloimmune thrombocytopenia. Thromb Haemost 1991, 65: 631-34. 3. Mir N, Samson D, House MJ, Kovar IZ. Failure of antinatal high-dose immunoglobulin to improve fetal platelet count in neonatal alloimmune thrombocytopenia. Vox Sang 1988; 55: 188-89. 4 Bussel JB, Berkowitz RL, McFarland JG, Lynch L, Chitkara U Antenatal treatment of neonatal alloimmune thrombocytopenia. N Engl J Med 1988; 319: 1374-78. 5. Poulain P, Kaplan C, Leberre C, Milon J, Bergeron C, Grall JY. Alloimmune thrombocytopenia m utero treatment by high doses of intravenous gamma globulins. Fetal Diagn Ther 1992; 7: 144-46. 6. Derycke M, Dreyfuss M, Ropert JC, Tchemia G. Intravenous immunoglobulin for neonatal isoimmune thrombocytopenia. Arch Dis Child 1985; 60: 667-69. 1 Herman JH,
Saene HKF, Stoutnebeek CP, Miranda DR, Zandstra DF, Langrehr D. Recent advances in the control of infection in patients with thoracic injury. Injury 1986; 17: 332-35. 3. Tetteroo GWM, Wagenvoort JHT, Castelein A, Tilanus HW, Ince C, Bruining HA. Selective decontamination to reduce gram negative colonisation and infections after oesophageal resection. Lancet 1990; 335: 704-07.
2.
van
Effect of inhaled corticosteroids on EBV-specific cytotoxic T cells and EBV oropharyngeal excretion SIR,-Inhaled corticosteroids are effective in chronic asthma, although the recommended doses can affect the hypothalamicpituitary-adrenal axis (HPA).l-8 We have studied 5 asthmatics who had used inhaled corticosteroids 300 g per day for more than 12 months, 14 other asthmatics treated differently, 5 control children in good health, and 10 nephrotic patients who were being treated with systemic glucocorticosteroids 0-5-1 mg/kg daily to evaluate the immunological effects of inhaled corticosteroids. All subjects were seropositive for Epstein-Barr virus (EBV). We examined oropharyngeal EBV excretion and the EBV-specific cytotoxic T-cell activity in peripheral blood. Umbilicalmononuclear cells converted into cell lines after exposure to the throat washings were examined for expression of EBV-specific nuclear antigens by anticomplement immunofluorescence.4,s Cellmediated immunity to EBV was assessed by T-cell-mediated regression of proliferating foci of exogenously infected autologous B cells.6 The data were expressed as a minimum number of originally seeded peripheral blood mononuclear cells required for 50%
regression (Reg)7 Positive cultures for oropharyngeal EBV were found in 84% of asthmatics using inhaled corticosteroids, 43% of asthmatics not on inhaled corticosteroids, 43% of controls, and 67% of the nephrotic patients (table). By contrast, EBV-specific cytotoxic T-cell activity was significantly decreased in nephrotic patients. The activity in patients who were on inhaled corticosteroids was slightly impaired, but the difference from that of healthy children was not significant. FREQUENCY OF TRANSFORMING EBV IN OROPHARYNGEAL EXCRETION AND EBV-SPECIFIC CYTOTOXIC T CELLS
Inhaled corticosteroids can adversely affect growth8 and bone formation9 in asthmatic patients. However, on strictly immunological or virological grounds, we believe that the results confirm that inhaled corticosteroids have the same degree of topical effects as, but fewer systemic effects than, systemic steroids. Oropharnygeal excretion of EBV did not correlate with the degree of impairment of T-cell immunity. Inhaled corticosteroids may act directly on pharnygeal cells that carry the agent in a latent state and may thus cause the virus to be reactivated.10 Department of Paediatrics, Nishi-Sapporo National Hospital, Sapporo, Japan; Department of Virology, Cancer Institute, Hokkaido University School of Medicine, and Department of Paediatrics, Sapporo Medical College, Sapporo
W. ABO S. IMAI M. SUGIURA N. TERAI T. OSATO Y. SHIMANO S. CHIBA
1. Tabachnik E, Zadik Z. Diurnal cortisol secretion dunng therapy with inhaled beclomethasone dipropionate in children with asthma. J Pediart 1991; 118: 294-97. 2 Vas R, Senior B, Morris M, Binkiewiz A. Adrenal effects of beclomethasone inhalation therapy in asthmatic children. J Pediatr 1982; 100: 660-62. 3. Wyatt R, Waschek J, Weinberger M, Sherman B. Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma. N Engl J Med 1978; 299: 1387-92. 4. Strauch B, Andrews LL, Siegel N, Miller G. Oropharyngeal excretion of Epstein-Barr virus by renal transplant recipients and other patients with immunosuppressive drugs. Lancet 1974; i: 234-37.
5. Reedman BM, Klein G. Cellular localization of an Epstein Barr virus (EBV) -associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines Int J Cancer 1973; 11: 499-520. 6. Moss DJ, Rickinson AB, Pope JH. Longterm T cell mediated immunity to Epstein-Barr virus in man. I. Complete regression of virus induced transformation in cultures of seropositive donor leukocytes. Int J Cancer 1978; 22: 662-68. 7. Rickinson AB, Crawford D, Epstein MA. Inhibition of the in vitro outgrowth of Epstem-Barr virus-transformed lymphocytes by thymus-dependent lymphocytes from infectious mononucleosis patients. Clin Exp Immunol 1977; 28: 72-79 8. Wales JKH, Barnes ND, Swift PGF. Growth retardation in children on steroids for asthma. Lancet 1991, 338: 1535. 9. Teelucksingh S. Padfield PL, Tibi L, Gough KJ, Holt PR. Inhaled corticosteroids, bone formation, and osteocalcin. Lancet 1991; 338: 60-61. 10. Bauer G. Induction of Epstein-Barr virus early antigens by corticosteroids: inhibition by TPA and retinoic acid. Int J Cancer 1983; 31: 291-95.
In-utero fetal therapy with immunoglobulin for alloimmune thrombocytopenia SiR,—In up to half the cases of alloimmune thrombocytopenia and cerebral haemorrhage, the haemorrhage occurs in utero.’ Preventive measures include early delivery by caesarean section, treatment of the mother with high-dose immunoglobulin and steroids, and weekly fetal platelet transfusion.2 Because intracranial haemorrhages can occur before week 20, early caesarean section is of limited benefit. The effect of steroids on the fetus is unclear. Fetal platelet transfusion should be reserved for high-risk cases and maternal IgG therapy is not only expensive but also of disputed efficacy.3 No reported cases show a rise in platelet count to more than 100 x 109/1.4,5 We report successful administration of immunoglobulin into the umbilical cord by cordocentesis. The first child of a 31-year-old mother, who was negative for the platelet alloantigen P1A1, had a neonatal cerebral haemorrhage associated with thrombocytopenia (minimum 10x 109/1). plalspecific antibodies were detected in the maternal serum; the husband was homozygous for P1A1 (Prof C. Muller-Eckhard, Institute for Transfusion Medicine, Giessen, Germany). In week 24 of the second pregnancy, cordocentesis showed a platelet count of 127 x 109/1; re-sampling in week 33 showed a fall to 51 x 109/1 despite consistently low antibody titres. With the mother’s informed consent, IgG (Endobulin, Immuno) was administered to the fetus, bringing the IgG concentration from 42 to 14-1 gfl (maternal concentration 124). Further cordocentesis in week 35 showed that the platelet count had risen to 130 x 109/1. IgG was 10g/1 and a further 0-5 g immunoglobulin was administered. A final cordocentesis was done at 37 weeks after collecting maternal platelets for fetal platelet transfusion. The transfusion was stopped when platelets reached 173 x 109/1. A healthy baby was delivered by caesarean section. The cord blood had 201 x 109/1 platelets and 11 ’9 g/1 IgG. Cranial ultrasound revealed no cerebral haemorrhage. Until day 8 the platelet count remained over 100 x 109/1. This case supports our hypothesis that, as in the postnatal situationdirect fetal administration of IgG produces a sustained increase in platelet count in alloimmune thrombocytopenia if higher IgG concentrations are achieved in the fetus than in the mother. Because of the long half-life of IgG, treatment intervals can be longer than those with platelet transfusions. The procedure not only carries a lower risk but costs are also acceptable. Department of Obstetrics, University Hospital,
R. ZIMMERMANN
8091 Zurich, Switzerland
A. HUCH
Jumbelic MI, Ancona RJ, Kickler TS. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8: 312-17 2. Bussel J, McFarland J. Recommendations for the evaluation and treatment of neonatal autoimmune and alloimmune thrombocytopenia. Thromb Haemost 1991, 65: 631-34. 3. Mir N, Samson D, House MJ, Kovar IZ. Failure of antinatal high-dose immunoglobulin to improve fetal platelet count in neonatal alloimmune thrombocytopenia. Vox Sang 1988; 55: 188-89. 4 Bussel JB, Berkowitz RL, McFarland JG, Lynch L, Chitkara U Antenatal treatment of neonatal alloimmune thrombocytopenia. N Engl J Med 1988; 319: 1374-78. 5. Poulain P, Kaplan C, Leberre C, Milon J, Bergeron C, Grall JY. Alloimmune thrombocytopenia m utero treatment by high doses of intravenous gamma globulins. Fetal Diagn Ther 1992; 7: 144-46. 6. Derycke M, Dreyfuss M, Ropert JC, Tchemia G. Intravenous immunoglobulin for neonatal isoimmune thrombocytopenia. Arch Dis Child 1985; 60: 667-69. 1 Herman JH,
