1212
glucose. The inaccuracy of feed composition prepared from a concentrated electrolyte solution was great; it bore no relation to mothers’ descriptions of how they diluted the solutions. The risk of a dangerously high level of osmolality was greater for the glucose electrolyte mixture. We now give a diluted electrolyte mixture to which parents only add sucrose. Sucrose electrolyte mixture is effective, of low osmotic load, and is also relatively cheap. It has been shown to be effective in more severely affected children in the developing world.5 We recommend its use in outpatient treatment of acute gastroenteritis in infancy.
the care of patients with haemophilia B. However, since thrombotic and haemorrhagic side-effects are recognised complications these products should not be used in patients who are thrombosis prone or who have D.t.c.. PHILIP M. BLATT Departments of Pathology and Medicine, GILBERT C. WHITE, II and Division of Hematology, JONATHAN C. GOLDSMITH University of North Carolina, HAROLD R. ROBERTS Chapel Hill, North Carolina 27514, U.S.A.
P. HUTCHINS B. LAWRIE T. H. J. MATTHEWS J. MANLY J. A. WALKER-SMITH
SiR,-Professor Scott and his colleagues, in their survey of the immunology of pre-eclampsia (April 1, p. 704), emphasise the possible importance of a hypoimmune response state. They cite evidence of unusual depression of cell-mediated immunity in women with severe pre-eclampsia, but they seem reluctant to come down on either the post hoc or the propter hoc side of the fence. Recent work from their own group in Leeds is mentioned only briefly but may, in fact, suggest the approach to determining whether there is a non-specific relative anergy or a more specific and restricted anomaly of immune responsiveness. They have demonstrated a protective effect of previous blood-transfusion’ and an abnormally low incidence of lymphocytotoxic HLA alloantibodies in severe pre-eclamptic pregnancies.2 Both of these observations tend to support Jeffcoate’s postulate3 that pre-eclampsia results from a failure of adaption. An important component of that adaptive process may be represented by the formation of alloantibodies to paternal transplantation antigens during normal pregnancy. Indeed the suggestion was made many years age4,1 that there are antibodies with properties of specific immunological enhancement which participate in the maintenance of mammalian viviparity. More effective "blocking" alloantibody production might be expected in women who have been previously sensitised by earlier pregnancies or by blood-transfusion; and hence perhaps they have a lesser incidence of pre-eclampsia. An adaptive process was implicit in the hypothesis of Clarke and Kirby6 that the balanced polymorphism for transplantation antigens is sustained in mammals by a selective system in which antigenic disparity between mother and conceptus is beneficial to fetal development. This hypothesis has been very strongly challenged,’ largely on the basis of experiments in rodents. But mice do not develop pre-eclampsia and mechanisms of fetal tolerance applicable to laboratory animals may be only partly applicable to the long human gestation period. The placental barrier functions poorly towards the end of human pregnancy as is indicated by the mechanisms of rhesus isoimmunisation. Further, the extent of depression of non-specific cell-mediated immunity in normal pregnancy8 is unlikely per se to account for the lack of a significant allograft rejection reaction. An additional fetus-specific tolerance mechanism makes good teleological sense and its inadequacy in immunologically inexperienced primigravidse is feasible as a major factor
Queen Elizabeth Hospital for Children, London E2 8PS
IMMUNOLOGY OF PRE-ECLAMPSIA
HOME MONITORING OF BLOOD-GLUCOSE
SiR,-Dr Tomkin’s letter (April 29, p. 936) should not be allowed to pass without any comment. Most investigators, who have looked critically at the accuracy of the "stix" methods of blood-glucose measurements, as assessed with a meter, have found good correlation between these measurements and standard laboratory techniques. Studies of visual assessment of colour change with ’Dextrpstix’ have shown that this is open to wide observer variation, and can give no more than a rough estimate of the blood-glucose concentration. Further more, while the cost of autoanalyser blood-sugar estimations may be only 4p, how many patients can carry this instrument around with them and how many hospitals can afford to have a supply of these to loan to the patients? Shrewsbury Hospital, Copthrone South, Shrewsbury
T. E. T. WEST
ANTITHROMBIN-III TRANSFUSION IN DISSEMINATED INTRAVASCULAR COAGULATION
SIR,-Dr Schipper and his colleagues (April 22, p. 854) report the successful treatment of bleeding secondary to disseminated intravascular coagulation (D.I.C.) with antithrombin III. The use of a pure preparation of antithrombin m (now available for clinical trial) for D.i.c. is logical, and the initial results are encouraging. The use of antithrombin in for D.i.c. followed by administration of prothrombin complex concentrates apparently resulted in hsemostasis in the patients described. In certain patients prothrombin complex concentrates can produce either thrombosis or D.i.c., and the risk of using prothrombin complex concentrates in the setting of D.I.C.’ is so significant that we urge discontinuation of clinical use of prothrombin complex concentrates in D.I.C. until the active ingredients in these concentrates are adequately delineated. It is unrealistic to believe that_normal antithrombin in levels will always prevent the known thromboembolic and/or hxmorrhagic side-effects sometimes associated with prothrombin complex concentrates. Indeed four recent cases of thrombosis or D.i.c. have recently occurred in the U.S.A. with the use of these products. Antithrombin 111 was measured in two of these patients at the time of the complications and was normal. The prothrombin complex concentrates have revolutionised 5. 1.
Chatterjee, A., Mahalanabis, D. Jalan, K. N., Maitra, T. K., Agarwa, S. K. ibid. 1977, i, 1333. Cederbaum, A. I., Blatt, P. M., Roberts, H. R. Ann. intern. Med. 1976, 84, 683.
.
in pre-eclampsia. If partial failure of an adaptive immunological enhancement process is one of the causes of the pre-eclampsia syndrome, it may be reasonable to propose the efficacy of specific immunotherapy in matings where there is not a high degree of consanguinity. Parenteral administration of a suitable preparation of isolated paternal lymphocytes, or more particularly B lymphocytes, should increase the maternal alloantibody reFeeney, J. G., Tovey, L. A. D., Scott, J. S. Lancet, 1977, i, 874. Jenkins, D. M., Need, J. A., Rajah, S. M. Clin. exp. Immun. 1977, 27, 485. 3. Jeffcoate, T. N. A. Proc. R. Soc. Med. 1966, 59, 397. 4. Kaliss, N., Dagg, M. K. Transplantation 1964, 2, 416. 5. Currie, G. A. in Fœtal Autonomy (Ciba Fndn. Symp) (edited by G. E. W. Wolstenholme and M. O’Connor); p.32. London, 1969. 6. Clarke, B. C., Kirby, D. R. S. Nature, 1966, 211, 999. 7. McLaren, A. in Immunobiology of Trophoblast (edited by R. G. Edwards, C. W. S. Howe, and M. H. Johnson). London, 1975. 8. Finn, R., St. Hill, C. A., Govan, A. J., Ralfs, I. G., Gurney, F. J., Denye, V. Br. med. J. 1972, iii, 150. 1. 2.
glucose. The inaccuracy of feed composition prepared from a concentrated electrolyte solution was great; it bore no relation to mothers’ descriptions of how they diluted the solutions. The risk of a dangerously high level of osmolality was greater for the glucose electrolyte mixture. We now give a diluted electrolyte mixture to which parents only add sucrose. Sucrose electrolyte mixture is effective, of low osmotic load, and is also relatively cheap. It has been shown to be effective in more severely affected children in the developing world.5 We recommend its use in outpatient treatment of acute gastroenteritis in infancy.
the care of patients with haemophilia B. However, since thrombotic and haemorrhagic side-effects are recognised complications these products should not be used in patients who are thrombosis prone or who have D.t.c.. PHILIP M. BLATT Departments of Pathology and Medicine, GILBERT C. WHITE, II and Division of Hematology, JONATHAN C. GOLDSMITH University of North Carolina, HAROLD R. ROBERTS Chapel Hill, North Carolina 27514, U.S.A.
P. HUTCHINS B. LAWRIE T. H. J. MATTHEWS J. MANLY J. A. WALKER-SMITH
SiR,-Professor Scott and his colleagues, in their survey of the immunology of pre-eclampsia (April 1, p. 704), emphasise the possible importance of a hypoimmune response state. They cite evidence of unusual depression of cell-mediated immunity in women with severe pre-eclampsia, but they seem reluctant to come down on either the post hoc or the propter hoc side of the fence. Recent work from their own group in Leeds is mentioned only briefly but may, in fact, suggest the approach to determining whether there is a non-specific relative anergy or a more specific and restricted anomaly of immune responsiveness. They have demonstrated a protective effect of previous blood-transfusion’ and an abnormally low incidence of lymphocytotoxic HLA alloantibodies in severe pre-eclamptic pregnancies.2 Both of these observations tend to support Jeffcoate’s postulate3 that pre-eclampsia results from a failure of adaption. An important component of that adaptive process may be represented by the formation of alloantibodies to paternal transplantation antigens during normal pregnancy. Indeed the suggestion was made many years age4,1 that there are antibodies with properties of specific immunological enhancement which participate in the maintenance of mammalian viviparity. More effective "blocking" alloantibody production might be expected in women who have been previously sensitised by earlier pregnancies or by blood-transfusion; and hence perhaps they have a lesser incidence of pre-eclampsia. An adaptive process was implicit in the hypothesis of Clarke and Kirby6 that the balanced polymorphism for transplantation antigens is sustained in mammals by a selective system in which antigenic disparity between mother and conceptus is beneficial to fetal development. This hypothesis has been very strongly challenged,’ largely on the basis of experiments in rodents. But mice do not develop pre-eclampsia and mechanisms of fetal tolerance applicable to laboratory animals may be only partly applicable to the long human gestation period. The placental barrier functions poorly towards the end of human pregnancy as is indicated by the mechanisms of rhesus isoimmunisation. Further, the extent of depression of non-specific cell-mediated immunity in normal pregnancy8 is unlikely per se to account for the lack of a significant allograft rejection reaction. An additional fetus-specific tolerance mechanism makes good teleological sense and its inadequacy in immunologically inexperienced primigravidse is feasible as a major factor
Queen Elizabeth Hospital for Children, London E2 8PS
IMMUNOLOGY OF PRE-ECLAMPSIA
HOME MONITORING OF BLOOD-GLUCOSE
SiR,-Dr Tomkin’s letter (April 29, p. 936) should not be allowed to pass without any comment. Most investigators, who have looked critically at the accuracy of the "stix" methods of blood-glucose measurements, as assessed with a meter, have found good correlation between these measurements and standard laboratory techniques. Studies of visual assessment of colour change with ’Dextrpstix’ have shown that this is open to wide observer variation, and can give no more than a rough estimate of the blood-glucose concentration. Further more, while the cost of autoanalyser blood-sugar estimations may be only 4p, how many patients can carry this instrument around with them and how many hospitals can afford to have a supply of these to loan to the patients? Shrewsbury Hospital, Copthrone South, Shrewsbury
T. E. T. WEST
ANTITHROMBIN-III TRANSFUSION IN DISSEMINATED INTRAVASCULAR COAGULATION
SIR,-Dr Schipper and his colleagues (April 22, p. 854) report the successful treatment of bleeding secondary to disseminated intravascular coagulation (D.I.C.) with antithrombin III. The use of a pure preparation of antithrombin m (now available for clinical trial) for D.i.c. is logical, and the initial results are encouraging. The use of antithrombin in for D.i.c. followed by administration of prothrombin complex concentrates apparently resulted in hsemostasis in the patients described. In certain patients prothrombin complex concentrates can produce either thrombosis or D.i.c., and the risk of using prothrombin complex concentrates in the setting of D.I.C.’ is so significant that we urge discontinuation of clinical use of prothrombin complex concentrates in D.I.C. until the active ingredients in these concentrates are adequately delineated. It is unrealistic to believe that_normal antithrombin in levels will always prevent the known thromboembolic and/or hxmorrhagic side-effects sometimes associated with prothrombin complex concentrates. Indeed four recent cases of thrombosis or D.i.c. have recently occurred in the U.S.A. with the use of these products. Antithrombin 111 was measured in two of these patients at the time of the complications and was normal. The prothrombin complex concentrates have revolutionised 5. 1.
Chatterjee, A., Mahalanabis, D. Jalan, K. N., Maitra, T. K., Agarwa, S. K. ibid. 1977, i, 1333. Cederbaum, A. I., Blatt, P. M., Roberts, H. R. Ann. intern. Med. 1976, 84, 683.
.
in pre-eclampsia. If partial failure of an adaptive immunological enhancement process is one of the causes of the pre-eclampsia syndrome, it may be reasonable to propose the efficacy of specific immunotherapy in matings where there is not a high degree of consanguinity. Parenteral administration of a suitable preparation of isolated paternal lymphocytes, or more particularly B lymphocytes, should increase the maternal alloantibody reFeeney, J. G., Tovey, L. A. D., Scott, J. S. Lancet, 1977, i, 874. Jenkins, D. M., Need, J. A., Rajah, S. M. Clin. exp. Immun. 1977, 27, 485. 3. Jeffcoate, T. N. A. Proc. R. Soc. Med. 1966, 59, 397. 4. Kaliss, N., Dagg, M. K. Transplantation 1964, 2, 416. 5. Currie, G. A. in Fœtal Autonomy (Ciba Fndn. Symp) (edited by G. E. W. Wolstenholme and M. O’Connor); p.32. London, 1969. 6. Clarke, B. C., Kirby, D. R. S. Nature, 1966, 211, 999. 7. McLaren, A. in Immunobiology of Trophoblast (edited by R. G. Edwards, C. W. S. Howe, and M. H. Johnson). London, 1975. 8. Finn, R., St. Hill, C. A., Govan, A. J., Ralfs, I. G., Gurney, F. J., Denye, V. Br. med. J. 1972, iii, 150. 1. 2.
