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DEFICIENCY
1256 these seem to supply another small indication for immunisation against measles. early ences as
Royal Hospital, Wolverhampton.
H. EVERLEY JONES.
DEFICIENCY SIR,-On reading through the correspondence section in the issue of Nov. 1,was most surprised to come across the " " use of the word what the Mental deficiency to describe Health Act of 1959 recognises as " subnormality ". I should be most interested to hear if there was any special reason why Dr. Jack Bavin used this in his letter, and why the Royal Medico-Psychological Association retain it as a description of one of their sections. Dr. Shapiro, of Harperbury Hospital, was described as chairman of the Mental Deficiency Section, Royal Medico-Psychological Association. I should have thought that there would have been good reasons for not using it. I am sure that its use does not in any way enhance the image of the specialty to " which it refers. Even the word " subnormality has its ]
Hollymoor Hospital, Birmingham 31.
TECWYN ROBERTS.
ABNORMAL FORMS OF FACTOR X SIR,-It has lately been shown that classic hxmophilia (hxmophilia A) and Christmas disease (haemophilia B) exist in two forms.1-7 In each disease immunological testing reveals a larger group in which no antigenic equivalent to the normal clotting-factor can be detected, and a smaller group in which a functionally inactive but antigenic equivalent to the normal clotting factor is present. In the smaller group of patients with Christmas disease who possess an antigenic equivalent to the normal clottingfactor, the plasma-samples have been found to have either a normal or an abnormal clotting-time with ox-brain thromboplastin, suggesting the presence of different abnormal forms of factor ix. Also, the plasma of two brothers with Christmas disease has shown the presence of an abnormal form of factor ix; but while the plasma of one brother had a normal clotting-time with ox-brain thromboplastin, the clotting-time of the other brother was prolonged. Likewise, in two siblings with haemophilia, the plasma of one contained an immunologically recognisable factor vin, whilst the plasma of the other lacked such material. Thus it has been suggested that a broader spectrum of structurally defective clotting-factors may be found both in haemophilia and in Christmas disease 2,7 and that patients may possess structurally defective forms of factors vm or ix which are not recognisable antigenically by immunological methods. The detection of structurally abnormal clotting-factors has now been extended to the " factor x defect " hitherto thought to be due to deficiency of factor x. Six patients diagnosed as having factor-x deficiency have been investigated using 5 methods of study: immunodiffusion techniques, neutralisation of factor-x antibody, techniques involving the activation of factor x by intrinsic clotting-factors, and extrinsic activation using tissueextract or Russell’s viper venom. The pattern of results of these tests is shown in the accompanying table. It can 1. 2. 3. 4. 5. 6. 7.
SUMMARY OF RESULTS IN SIX PATIENTS WITH THE FACTOR-X DEFECT
Denson, K. W. E. Lancet, 1968, ii, 222. Denson, K. W. E., Biggs, R., Haddon, M. E., Borrett, R., Cobb, K. Br. J. Hœmat. 1969, 17, 163. Hoyer, L. W., Breckenridge, R. T. Blood, 38, 962. Denson, K. W. E., Biggs, R., Mannucci, P. M. J. clin. Path. 1968, 21, 160. Hougie, C., Twomey, J. J. Lancet, 1967, i, 698. Roberts, H. R., Grizzle, J. E., McLester, W. D., Penick, G. D. J. clin. Invest, 1968, 47, 360. Pfueller, S., Somer, J. B., Castaldi, P. A. Coagulation, 1969, 2, 213.
Abn. =abnormal. SI. abn. =slightly abnormal. R.V.V. =Russell’s viper venom.
be
only two of the patients clotting-times of all the considerably shortened by the
that the samples from the The same results. gave seen
plasma-samples
were
addition of purified factor x,
indicating that no new hypothetical clotting-factor was involved; and assays for the intrinsic clotting-factors xii, xi, VIII, and ix were within normal limits, thus excluding the complication of multiple deficiencies. The heterogeneity within these six samples suggests that the factor-x defect is not due simply to deficiency of factor x, but to the presence of different structurally defective factor-x molecules produced as the result of different genetic mutations. The full results of this work will be elsewhere. Oxford Haemophilia Centre, Churchill Hospital, Oxford.
published
in detail
K. W. E. DENSON.
INTESTINAL METHYLATION OF FOLATES were interested in the comments of Dr. Baker and Dr. Frank (Nov. 22, p. 1135) on our article (Oct. 11, p. 776). The excellent study of folate absorption reported by their group in 1965showed that high levels of Lactobacillus casei-active material, presumably methyltetrahydrofolate, appeared in plasma after very large oral or parenteral doses of pteroylglutamic acid and other analogues. This study, however, does not provide any evidence that the methyl folate arose by conversion of the test dose rather than by exchange with tissue methyltetrahydrofolate, and hence cannot be said to have demonstrated conversion of ingested folates to the methylated form.
SIR,-We
’
St.
Department of Hæmatology, Mary’s Hospital Medical School, London W.2.
I. CHANARIN
JANET PERRY.
EFFECT OF NEPHRECTOMY ON TRANSFUSION REQUIREMENTS OF DIALYSIS PATIENTS were interested in Dr. van Ypersele de Strihou SIR,-We and Mr. Stragier’s answer (Nov. 29, p. 1191) to our letter2 on their paper.3 I am sure they will be interested to know that, in our experience, it is now possible to avoid a fall in haematocrit in patients starting hsemodialysis even if this has been preceded by a transfusion. Instead, we have observed a sustained rise in haematocrit to an average of30% within three months. We attribute this change from our previously reported experience4 to the routine use of Baker, H., Frank, O., Feingold, S., Ziffer, H., Gellene, R., Leevy, C. Sobotka, H. Am. J. clin. Nutr. 1965, 17, 88. 2. Shaldon, S. Lancet, Oct. 18, 1969, p. 849. 3. van Ypersele de Strihou, C., Stragier, A. ibid. Oct. 4, 1969, p. 705. 4. Crocket, R. E., Baillod, R. A., Lee, B. N., Moorhead, J. F., Stevenson, C. M., Vorghese, Z., Shaldon, S. Proc. Europ. Dial. Transpl. Ass. 1967, 4, 17. 1.
Royal Hospital, Wolverhampton.
H. EVERLEY JONES.
DEFICIENCY SIR,-On reading through the correspondence section in the issue of Nov. 1,was most surprised to come across the " " use of the word what the Mental deficiency to describe Health Act of 1959 recognises as " subnormality ". I should be most interested to hear if there was any special reason why Dr. Jack Bavin used this in his letter, and why the Royal Medico-Psychological Association retain it as a description of one of their sections. Dr. Shapiro, of Harperbury Hospital, was described as chairman of the Mental Deficiency Section, Royal Medico-Psychological Association. I should have thought that there would have been good reasons for not using it. I am sure that its use does not in any way enhance the image of the specialty to " which it refers. Even the word " subnormality has its ]
Hollymoor Hospital, Birmingham 31.
TECWYN ROBERTS.
ABNORMAL FORMS OF FACTOR X SIR,-It has lately been shown that classic hxmophilia (hxmophilia A) and Christmas disease (haemophilia B) exist in two forms.1-7 In each disease immunological testing reveals a larger group in which no antigenic equivalent to the normal clotting-factor can be detected, and a smaller group in which a functionally inactive but antigenic equivalent to the normal clotting factor is present. In the smaller group of patients with Christmas disease who possess an antigenic equivalent to the normal clottingfactor, the plasma-samples have been found to have either a normal or an abnormal clotting-time with ox-brain thromboplastin, suggesting the presence of different abnormal forms of factor ix. Also, the plasma of two brothers with Christmas disease has shown the presence of an abnormal form of factor ix; but while the plasma of one brother had a normal clotting-time with ox-brain thromboplastin, the clotting-time of the other brother was prolonged. Likewise, in two siblings with haemophilia, the plasma of one contained an immunologically recognisable factor vin, whilst the plasma of the other lacked such material. Thus it has been suggested that a broader spectrum of structurally defective clotting-factors may be found both in haemophilia and in Christmas disease 2,7 and that patients may possess structurally defective forms of factors vm or ix which are not recognisable antigenically by immunological methods. The detection of structurally abnormal clotting-factors has now been extended to the " factor x defect " hitherto thought to be due to deficiency of factor x. Six patients diagnosed as having factor-x deficiency have been investigated using 5 methods of study: immunodiffusion techniques, neutralisation of factor-x antibody, techniques involving the activation of factor x by intrinsic clotting-factors, and extrinsic activation using tissueextract or Russell’s viper venom. The pattern of results of these tests is shown in the accompanying table. It can 1. 2. 3. 4. 5. 6. 7.
SUMMARY OF RESULTS IN SIX PATIENTS WITH THE FACTOR-X DEFECT
Denson, K. W. E. Lancet, 1968, ii, 222. Denson, K. W. E., Biggs, R., Haddon, M. E., Borrett, R., Cobb, K. Br. J. Hœmat. 1969, 17, 163. Hoyer, L. W., Breckenridge, R. T. Blood, 38, 962. Denson, K. W. E., Biggs, R., Mannucci, P. M. J. clin. Path. 1968, 21, 160. Hougie, C., Twomey, J. J. Lancet, 1967, i, 698. Roberts, H. R., Grizzle, J. E., McLester, W. D., Penick, G. D. J. clin. Invest, 1968, 47, 360. Pfueller, S., Somer, J. B., Castaldi, P. A. Coagulation, 1969, 2, 213.
Abn. =abnormal. SI. abn. =slightly abnormal. R.V.V. =Russell’s viper venom.
be
only two of the patients clotting-times of all the considerably shortened by the
that the samples from the The same results. gave seen
plasma-samples
were
addition of purified factor x,
indicating that no new hypothetical clotting-factor was involved; and assays for the intrinsic clotting-factors xii, xi, VIII, and ix were within normal limits, thus excluding the complication of multiple deficiencies. The heterogeneity within these six samples suggests that the factor-x defect is not due simply to deficiency of factor x, but to the presence of different structurally defective factor-x molecules produced as the result of different genetic mutations. The full results of this work will be elsewhere. Oxford Haemophilia Centre, Churchill Hospital, Oxford.
published
in detail
K. W. E. DENSON.
INTESTINAL METHYLATION OF FOLATES were interested in the comments of Dr. Baker and Dr. Frank (Nov. 22, p. 1135) on our article (Oct. 11, p. 776). The excellent study of folate absorption reported by their group in 1965showed that high levels of Lactobacillus casei-active material, presumably methyltetrahydrofolate, appeared in plasma after very large oral or parenteral doses of pteroylglutamic acid and other analogues. This study, however, does not provide any evidence that the methyl folate arose by conversion of the test dose rather than by exchange with tissue methyltetrahydrofolate, and hence cannot be said to have demonstrated conversion of ingested folates to the methylated form.
SIR,-We
’
St.
Department of Hæmatology, Mary’s Hospital Medical School, London W.2.
I. CHANARIN
JANET PERRY.
EFFECT OF NEPHRECTOMY ON TRANSFUSION REQUIREMENTS OF DIALYSIS PATIENTS were interested in Dr. van Ypersele de Strihou SIR,-We and Mr. Stragier’s answer (Nov. 29, p. 1191) to our letter2 on their paper.3 I am sure they will be interested to know that, in our experience, it is now possible to avoid a fall in haematocrit in patients starting hsemodialysis even if this has been preceded by a transfusion. Instead, we have observed a sustained rise in haematocrit to an average of30% within three months. We attribute this change from our previously reported experience4 to the routine use of Baker, H., Frank, O., Feingold, S., Ziffer, H., Gellene, R., Leevy, C. Sobotka, H. Am. J. clin. Nutr. 1965, 17, 88. 2. Shaldon, S. Lancet, Oct. 18, 1969, p. 849. 3. van Ypersele de Strihou, C., Stragier, A. ibid. Oct. 4, 1969, p. 705. 4. Crocket, R. E., Baillod, R. A., Lee, B. N., Moorhead, J. F., Stevenson, C. M., Vorghese, Z., Shaldon, S. Proc. Europ. Dial. Transpl. Ass. 1967, 4, 17. 1.