46 COLD AND TIC DOULOUREUX
SIR,-Sufferers from tic douloureux may be
interested in
a
simple method which has kept me pain-free for over a year. Knowing the very low threshold for touch, I wondered if temperature change could trigger the nerve as well, and in my case
avoiding sudden cold has been most effective. This means, not going into an air-conditioned room, not using ice in drinks, avoiding cold winds, not swimming in cold water, and so on.
first envisaged. We agree with Professor Caen and Dr Sultan about the need for further studies. A L. i RtnDM A. BLOOM I. R. PEAKE J. C. GIDDINGS Department of Hæmatology, SONIA A. M. SHEARN of University Hospital Wales, Heath Park, Cardiff CF4 4XW. E. G. D. TUDDENHA
SCREENING FOR NEURAL-TUBE DEFECTS
I do not think that this is a spontaneous remission because if the affected cheek is unavoidably exposed to sudden cold, the
pain recurs. Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Chemin Cote St. Catherine Road, Montreal, Quebec H3T 1E2, Canada.
S!R,—Ifully support Dr Seller’s criticisms (Dec. 6, of the paper by Leighton et 1.’ on the potential of maternal-blood a-fetoprotein (A.F.P.) in screening for neuraltube defects. What is principally at issue in assessing the value of this procedure is the number of cases of open spina bifida where A.F.P. concentrations lie above a defined upper limit of normal. Why Leighton et al. should feel that "for the first time some tentative observations on the practical use of A.F.P. estimation in maternal blood using the results of a single laboratory" are possible when they have only analysed 6 cases of spina bifida, is not clear. What is clear is that their results are at variance with a much larger study, also based on a single
p.1141)
NAOMI FITCH
ENDOTHELIAL CELLS AND FACTOR-VIII-RELATED PROTEIN on the of von disease Willebrand’s (vWd) proposed by pathogenesis Professor Caen and Dr Sultan (]3ec. 6, p. 1129). The association between factor-vin-reiated antigen and the vascular endothelium is well established’and the synthesis by endothelial cells of this and the ristocetin platelet-aggregation cofactor has been described.34 These activities are quite possibly functions of the same molecule, sometimes referred to as factor-vin-reiated protein or von Willebrand factor.5 In several patients with vWd with prolonged bleeding-time, defective ristocetin-induced platelet aggregation, and detectable levels of factor-vm-retated protein we have found that the factor-viii-related protein is abnormal and has increased anodal electrophoretic mobility. 6The suggestion of Professor Caen and Dr Sultan that vWd is a result of an endothelial-cell defect is entirely reasonable. We have done further studies on factor-vin-reiated protein synthesised in cultures of normal endothelial cells. In four cultures derived from different umbilical cords, factor-viii-related protein was detected in the culture medium and active synthesis was demonstrated by the incorporation of 335-methionine into specific immunoprecipitate. This factor-vm-related protein showed a reaction of immunological identity with that found in normal plasma. However, its electrophoretic mobility demonstrated on crossed immunoelectrophoresis was abnormal, being-- more anodic than factor-viii-related protein in normal adult or cord plasma or serum. Factor-vm-retated protein produced by normal fetal endothelial cells in culture and that present in some plasmas thus have certain features in common. These include increased anodal mobility and apparently normal subunits on reduction8 although the vWd protein does not support ristocetin platelet aggregation. It thus seems that the presence of apparently normal subunits does not necessarily indicate that the molecules of factor-vin-related protein are identical. It seems that the material produced by endothelial cells in our cultures is a little different from that which appears in plasma as normal factor-viii-related protein suggesting that it may be further processed in some way. Although the primary defect in vWd may reside in the endothelial cell, this hypothesis does not explain the results of transfusion, and the situation seems to be more complex than at
SIR,-We have read with interest the hypothesis
laboratory,2
Bloom, A. L., Giddings,, J. C., Wilks, C. J. Nature New Biology, 1973, 241,
2.
L. W., de los Santos, R. P., Hoyer, J. R. J. clin. Invest. 1973, 52, 2737. Jaffe, E. A., Hoyer, L. W., Nachman, R. L. ibid. p. 2757. Jaffe, E. A., Nachman, R. L. ibid. 1975, 56, 698. Bloom, A. L., Peake, I. R., Giddings, J. C. Lancet, 1974, i, 576. Peake, I. R., Bloom, A. L., Giddings, J. C. New Engl. J. Med. 1974, 291, 113. Peake, I. R., Bloom, A. L., Giddings, J. C. in Abstracts of the Vth Congress International Society of Thrombosis and Hæmostasis, Paris 1975; p. 412. Gralnick, H. R., Coller, B. S., Sutton, Y. J. clin. Invest. 1975, 56, 814.
217.
3. 4. 5. 6. 7.
8.
Hoyer,
published experience.
NUMBER OF CASES OF OPEN SPINA BIFIDA AND ANENCEPHALY WHERE MATERNAL-BLOOD A.F.P. WAS MEASURED BETWEEN
15
AND
20
WEEKS OF
PREGNANCY.
Cases where A.F.P.S
were
outside the normal range
are
shown in
parentheses.
The table shows the total number of published cases of both spina bifida and anencephaly where maternal-blood A.F.P. was outside a normal range between 15 and 20 weeks of gestation. This time period is chosen because A.F.P. does not begin to rise in abnormal pregnancies until the end of the first trimester2 and because termination of pregnancy is undesirable after the 20th week. The conclusions from the table are less optimistic than those of Leighton et al.; in particular the table shows a 47% detection-rate for spina bifida against the 80% which Leighton et al. recorded. The 80% figure is not very different from the success-rate which we recorded 18 months ago when we were at a comparable level of experience. Though it is probable that detection-rates will improve with better technology and in carefully controlled prospective studies, an objective assessment of screening will not be possible until many more results have been collected. It is to this end that the U.K. Colopen
1. 2.
1.
and indeed with cumulative
Leighton, P. C., Gordon, Y. B., Kitau, M. J., Leek, A. E., Chard, T. Lancet, 1975, ii, 1012. Brock, D. J. H., Scrimgeour, J. B., Bolton, A. E., Wald, N. J., Peto, R.,
Barker, S. ibid. 1975, ii, 195. 3. Brock, D. J. H., Bolton, A. E., Monaghan, J. M. ibid. 1973, ii, 923. 4. Seller, M. J., Singer, J. D., Coltart, T. M., Campbell, S. ibid. 1974, i, 428. 5. Harris, R., Jennison, R. F., Barson, A. J., Laurence, K. M., Ruoslahti, E.,
Seppala, M. ibid. 1974, i, 429. Wald, N. J., Brock, D. J. H., Bonnar, J. ibid. 1974, i, 765. Brock, D. J. H., Bolton, A. E., Scrimgeour, J. B. ibid. 1974, i, 767. Cowchock, F. S., Jackson, L. G. ibid. 1974, ii, 48. Leek, A. E., Leighton, P. C., Kitau, M. J., Chard, T. ibid. 1974, ii, 1511. Vince, J. D., McManus, T. J., Ferguson-Smith, M. A., Ratcliffe, J. G. Br. J. Obstet. Gynœc. 1975, 82, 718. 11. Campbell, S., Pruse Davies, J., Coltart, T. M., Seller, M. J., Singer, J. D. Lancet, 1975, i, 1065
6. 7. 8. 9. 10.
SIR,-Sufferers from tic douloureux may be
interested in
a
simple method which has kept me pain-free for over a year. Knowing the very low threshold for touch, I wondered if temperature change could trigger the nerve as well, and in my case
avoiding sudden cold has been most effective. This means, not going into an air-conditioned room, not using ice in drinks, avoiding cold winds, not swimming in cold water, and so on.
first envisaged. We agree with Professor Caen and Dr Sultan about the need for further studies. A L. i RtnDM A. BLOOM I. R. PEAKE J. C. GIDDINGS Department of Hæmatology, SONIA A. M. SHEARN of University Hospital Wales, Heath Park, Cardiff CF4 4XW. E. G. D. TUDDENHA
SCREENING FOR NEURAL-TUBE DEFECTS
I do not think that this is a spontaneous remission because if the affected cheek is unavoidably exposed to sudden cold, the
pain recurs. Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 Chemin Cote St. Catherine Road, Montreal, Quebec H3T 1E2, Canada.
S!R,—Ifully support Dr Seller’s criticisms (Dec. 6, of the paper by Leighton et 1.’ on the potential of maternal-blood a-fetoprotein (A.F.P.) in screening for neuraltube defects. What is principally at issue in assessing the value of this procedure is the number of cases of open spina bifida where A.F.P. concentrations lie above a defined upper limit of normal. Why Leighton et al. should feel that "for the first time some tentative observations on the practical use of A.F.P. estimation in maternal blood using the results of a single laboratory" are possible when they have only analysed 6 cases of spina bifida, is not clear. What is clear is that their results are at variance with a much larger study, also based on a single
p.1141)
NAOMI FITCH
ENDOTHELIAL CELLS AND FACTOR-VIII-RELATED PROTEIN on the of von disease Willebrand’s (vWd) proposed by pathogenesis Professor Caen and Dr Sultan (]3ec. 6, p. 1129). The association between factor-vin-reiated antigen and the vascular endothelium is well established’and the synthesis by endothelial cells of this and the ristocetin platelet-aggregation cofactor has been described.34 These activities are quite possibly functions of the same molecule, sometimes referred to as factor-vin-reiated protein or von Willebrand factor.5 In several patients with vWd with prolonged bleeding-time, defective ristocetin-induced platelet aggregation, and detectable levels of factor-vm-retated protein we have found that the factor-viii-related protein is abnormal and has increased anodal electrophoretic mobility. 6The suggestion of Professor Caen and Dr Sultan that vWd is a result of an endothelial-cell defect is entirely reasonable. We have done further studies on factor-vin-reiated protein synthesised in cultures of normal endothelial cells. In four cultures derived from different umbilical cords, factor-viii-related protein was detected in the culture medium and active synthesis was demonstrated by the incorporation of 335-methionine into specific immunoprecipitate. This factor-vm-related protein showed a reaction of immunological identity with that found in normal plasma. However, its electrophoretic mobility demonstrated on crossed immunoelectrophoresis was abnormal, being-- more anodic than factor-viii-related protein in normal adult or cord plasma or serum. Factor-vm-retated protein produced by normal fetal endothelial cells in culture and that present in some plasmas thus have certain features in common. These include increased anodal mobility and apparently normal subunits on reduction8 although the vWd protein does not support ristocetin platelet aggregation. It thus seems that the presence of apparently normal subunits does not necessarily indicate that the molecules of factor-vin-related protein are identical. It seems that the material produced by endothelial cells in our cultures is a little different from that which appears in plasma as normal factor-viii-related protein suggesting that it may be further processed in some way. Although the primary defect in vWd may reside in the endothelial cell, this hypothesis does not explain the results of transfusion, and the situation seems to be more complex than at
SIR,-We have read with interest the hypothesis
laboratory,2
Bloom, A. L., Giddings,, J. C., Wilks, C. J. Nature New Biology, 1973, 241,
2.
L. W., de los Santos, R. P., Hoyer, J. R. J. clin. Invest. 1973, 52, 2737. Jaffe, E. A., Hoyer, L. W., Nachman, R. L. ibid. p. 2757. Jaffe, E. A., Nachman, R. L. ibid. 1975, 56, 698. Bloom, A. L., Peake, I. R., Giddings, J. C. Lancet, 1974, i, 576. Peake, I. R., Bloom, A. L., Giddings, J. C. New Engl. J. Med. 1974, 291, 113. Peake, I. R., Bloom, A. L., Giddings, J. C. in Abstracts of the Vth Congress International Society of Thrombosis and Hæmostasis, Paris 1975; p. 412. Gralnick, H. R., Coller, B. S., Sutton, Y. J. clin. Invest. 1975, 56, 814.
217.
3. 4. 5. 6. 7.
8.
Hoyer,
published experience.
NUMBER OF CASES OF OPEN SPINA BIFIDA AND ANENCEPHALY WHERE MATERNAL-BLOOD A.F.P. WAS MEASURED BETWEEN
15
AND
20
WEEKS OF
PREGNANCY.
Cases where A.F.P.S
were
outside the normal range
are
shown in
parentheses.
The table shows the total number of published cases of both spina bifida and anencephaly where maternal-blood A.F.P. was outside a normal range between 15 and 20 weeks of gestation. This time period is chosen because A.F.P. does not begin to rise in abnormal pregnancies until the end of the first trimester2 and because termination of pregnancy is undesirable after the 20th week. The conclusions from the table are less optimistic than those of Leighton et al.; in particular the table shows a 47% detection-rate for spina bifida against the 80% which Leighton et al. recorded. The 80% figure is not very different from the success-rate which we recorded 18 months ago when we were at a comparable level of experience. Though it is probable that detection-rates will improve with better technology and in carefully controlled prospective studies, an objective assessment of screening will not be possible until many more results have been collected. It is to this end that the U.K. Colopen
1. 2.
1.
and indeed with cumulative
Leighton, P. C., Gordon, Y. B., Kitau, M. J., Leek, A. E., Chard, T. Lancet, 1975, ii, 1012. Brock, D. J. H., Scrimgeour, J. B., Bolton, A. E., Wald, N. J., Peto, R.,
Barker, S. ibid. 1975, ii, 195. 3. Brock, D. J. H., Bolton, A. E., Monaghan, J. M. ibid. 1973, ii, 923. 4. Seller, M. J., Singer, J. D., Coltart, T. M., Campbell, S. ibid. 1974, i, 428. 5. Harris, R., Jennison, R. F., Barson, A. J., Laurence, K. M., Ruoslahti, E.,
Seppala, M. ibid. 1974, i, 429. Wald, N. J., Brock, D. J. H., Bonnar, J. ibid. 1974, i, 765. Brock, D. J. H., Bolton, A. E., Scrimgeour, J. B. ibid. 1974, i, 767. Cowchock, F. S., Jackson, L. G. ibid. 1974, ii, 48. Leek, A. E., Leighton, P. C., Kitau, M. J., Chard, T. ibid. 1974, ii, 1511. Vince, J. D., McManus, T. J., Ferguson-Smith, M. A., Ratcliffe, J. G. Br. J. Obstet. Gynœc. 1975, 82, 718. 11. Campbell, S., Pruse Davies, J., Coltart, T. M., Seller, M. J., Singer, J. D. Lancet, 1975, i, 1065
6. 7. 8. 9. 10.
