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FOLIC-ACID ABSORPTION IN MAN
459 control. The results have been promising. In three cases the movements have been almost totally abolished and in the fourth they have been strikingly reduced. This control has been achieved without undesirable sedation, the only side-effects being other extrapyramidal effects (opisthotonos in one patient, and hypertonicity in another). Reduction of the maintenance dose relieved these side-effects without significantly lessening the therapeutic benefit. The average maintenance dose has been 1 mg. t.d.s. Serial bloodcounts have shown no disturbance of the blood-picture. No postural hypotension has been seen. SH. TARIGHATI Springfield Hospital, M. F. A’BROOK. London S.W.17.
would not affect a pair-fed control would produce death of an E.F.A.-deficient rat from nephrocalcinosis in two weeks, and there was metastatic calcification in other tissues, including the aortic media. Therefore, I suggested that if the diet contains sufficient vitamin D, E.F.A.-deficiency could produce Monckeberg’s sclerosis, which in younger persons is associated with conditions that are known to increase E.F.A.-requirement (debilitating diseases such as carcinoma, diabetes mellitus, and chronic infections). The case for E.F.A. being concerned with atheroma and with coronary heart-disease4 is greatly strengthened by the recently reported results of prospective trials.&a cute; HUGH SINCLAIR. Oxford.
RING-CHROMOSOME FORMATION
FOLIC-ACID ABSORPTION IN MAN SiR,—I read with interest the paper by Dr. Hepner and his colleagues (Aug. 10, p. 302). I should like to comment on the kinetic aspects of their interpretation of the results. It is unconventional to use logarithms when plotting reciprocals of absorption-rate against luminal concentration in the Lineweaver-Burk analysis, to which they refer. Furthermore, I do not think it is possible to derive quantitative information about Km and Vniax from such a graph. The straight-line relation between reciprocals can be
involuntary
SIR,-Dr. Warren (Aug. 10, p. 350) states that there is no evidence that ring-chromosome formation follows terminal deletions. I have observed a c-metaphase of a human lymphocyte in which there were two large acentric fragments and a ring, and one A.1 chromosome was absent (see accompanying
expressed mathematically as where v=reaction-rate (absorption rate); s=substrate concentration and Km and V. have their usual meaning and are constants for any given experimental conditions. With a minor alteration, this can be converted into logarithms thus:
It follows
log -
log - S3
a straight plotted against line will result only if s is small compared with Km. This may be the situation which the authors have studied. However, even if it is, the intercept on the vertical axis can give an
v:: impossible estimate of
Cell showing ring chromosome (R) and 2 ments
large acentric frag-
(F).
figure). It is hard to resist the conclusion that the ring was formed by union of the two ends of the centric fragment, following a break in each arm of the chromosome. The two acentric fragments would have been lost had the cell not been fixed in metaphase. Other cells examined in this preparation did not have a ring chromosome. The preparation was made from a patient who had received 32P treatment for polycvthaemia vera. University Department of Anatomy, Medical School, The University, Newcastle upon Tyne 1.
J. E. GRAY.
ESSENTIAL FATTY ACIDS AND ATHEROMA
SIR,-Mr. McCullagh (Aug. 10,
that a been suggested as a cause of arterial medial degeneration and calcification ". I discussed this possibility seven years ago.1 In Monckeberg’s sclerosis the calcification is found particularly in the elastic fibres of the media between the muscle-fibres. Duguid2 produced in the rat lesions resembling Monckeberg’s sclerosis in man by feeding excess vitamin D and calcium; the lesions were " frequently accompanied by intimal changes resembling those of atheroma ". I found3 that rats deficient in E.F.A. were much more sensitive to vitamin D: a dose that p.
353)
is
not aware
decrease in essential fatty acids (E.F.A.) in tissues has "
1. 2. 3.
Sinclair, H. M. Trans. med. Soc. Lond. 1960-61, 77, 612. Duguid, J. B. J. Path. Bact. 1930, 33, 697. Sinclair, H. M. Lancet, 1956, ii, 101.
ever
that, if
and not
is
V max itself, and it would
seem
to derive values for both factors. The authors have clearly shown evidence of a saturable reaction of some sort in the jejunum, but I wonder why they have not analysed their results in the conventional way. St. Bartholomew’s Hospital, G. E. SLADEN. London E.C.1.
TREATMENT OF SEVERE PHYSOSTIGMINE POISONING SIR,-In the management of a severe case of physostigmine poisoning Dr. Cumming and his colleagues (July 20, p. 147) were obliged to discontinue two attempts at treatment with atropine because it produced tachycardia and multifocal ventricular extrasystoles. Their action was fully justified, since it is known that administration of atropine in the presence of hypoxia may lead to ventricular tachycardia and fibrillation.7 Withholding the atropine may, however,jeopardise efforts to save the patient’s life, since it is not always possible to achieve immediate and adequate ventilation. Even after the establishment of tracheostomy and artificial respiration sudden secretions may cause dangerous bouts of cyanosis. I should like to suggest in such cases the use of propranolol: a slow intravenous injection of 5 mg. may not only reduce the high pulse-rate but also avert the danger of ventricular fibrillation. In a similar case 8I have used propranolol to Sinclair, H. M. ibid. 1956, i, 381. Leren, P. Acta med. scand. 1966, 180, suppl. 466. Turpeinen, O., Miettinen, M., Karvonen, M. J., Roine, P., Pekkarinen, M., Lehtosuo, E. J., Alivirta, P. Am. J. clin. Nutr. 1968, 21, 255. 6. Crowley, W. J., Johns, T. R. Archs Neurol., Chicago, 1966, 14, 611. 7. Wills, J. H., McNamara, B. P., Fine, E. A. Fedn Proc. 1950, 9, 136. 8. Valero, A. Israel J. med. Sci. 1967, 3, 582.
4. 5.
would not affect a pair-fed control would produce death of an E.F.A.-deficient rat from nephrocalcinosis in two weeks, and there was metastatic calcification in other tissues, including the aortic media. Therefore, I suggested that if the diet contains sufficient vitamin D, E.F.A.-deficiency could produce Monckeberg’s sclerosis, which in younger persons is associated with conditions that are known to increase E.F.A.-requirement (debilitating diseases such as carcinoma, diabetes mellitus, and chronic infections). The case for E.F.A. being concerned with atheroma and with coronary heart-disease4 is greatly strengthened by the recently reported results of prospective trials.&a cute; HUGH SINCLAIR. Oxford.
RING-CHROMOSOME FORMATION
FOLIC-ACID ABSORPTION IN MAN SiR,—I read with interest the paper by Dr. Hepner and his colleagues (Aug. 10, p. 302). I should like to comment on the kinetic aspects of their interpretation of the results. It is unconventional to use logarithms when plotting reciprocals of absorption-rate against luminal concentration in the Lineweaver-Burk analysis, to which they refer. Furthermore, I do not think it is possible to derive quantitative information about Km and Vniax from such a graph. The straight-line relation between reciprocals can be
involuntary
SIR,-Dr. Warren (Aug. 10, p. 350) states that there is no evidence that ring-chromosome formation follows terminal deletions. I have observed a c-metaphase of a human lymphocyte in which there were two large acentric fragments and a ring, and one A.1 chromosome was absent (see accompanying
expressed mathematically as where v=reaction-rate (absorption rate); s=substrate concentration and Km and V. have their usual meaning and are constants for any given experimental conditions. With a minor alteration, this can be converted into logarithms thus:
It follows
log -
log - S3
a straight plotted against line will result only if s is small compared with Km. This may be the situation which the authors have studied. However, even if it is, the intercept on the vertical axis can give an
v:: impossible estimate of
Cell showing ring chromosome (R) and 2 ments
large acentric frag-
(F).
figure). It is hard to resist the conclusion that the ring was formed by union of the two ends of the centric fragment, following a break in each arm of the chromosome. The two acentric fragments would have been lost had the cell not been fixed in metaphase. Other cells examined in this preparation did not have a ring chromosome. The preparation was made from a patient who had received 32P treatment for polycvthaemia vera. University Department of Anatomy, Medical School, The University, Newcastle upon Tyne 1.
J. E. GRAY.
ESSENTIAL FATTY ACIDS AND ATHEROMA
SIR,-Mr. McCullagh (Aug. 10,
that a been suggested as a cause of arterial medial degeneration and calcification ". I discussed this possibility seven years ago.1 In Monckeberg’s sclerosis the calcification is found particularly in the elastic fibres of the media between the muscle-fibres. Duguid2 produced in the rat lesions resembling Monckeberg’s sclerosis in man by feeding excess vitamin D and calcium; the lesions were " frequently accompanied by intimal changes resembling those of atheroma ". I found3 that rats deficient in E.F.A. were much more sensitive to vitamin D: a dose that p.
353)
is
not aware
decrease in essential fatty acids (E.F.A.) in tissues has "
1. 2. 3.
Sinclair, H. M. Trans. med. Soc. Lond. 1960-61, 77, 612. Duguid, J. B. J. Path. Bact. 1930, 33, 697. Sinclair, H. M. Lancet, 1956, ii, 101.
ever
that, if
and not
is
V max itself, and it would
seem
to derive values for both factors. The authors have clearly shown evidence of a saturable reaction of some sort in the jejunum, but I wonder why they have not analysed their results in the conventional way. St. Bartholomew’s Hospital, G. E. SLADEN. London E.C.1.
TREATMENT OF SEVERE PHYSOSTIGMINE POISONING SIR,-In the management of a severe case of physostigmine poisoning Dr. Cumming and his colleagues (July 20, p. 147) were obliged to discontinue two attempts at treatment with atropine because it produced tachycardia and multifocal ventricular extrasystoles. Their action was fully justified, since it is known that administration of atropine in the presence of hypoxia may lead to ventricular tachycardia and fibrillation.7 Withholding the atropine may, however,jeopardise efforts to save the patient’s life, since it is not always possible to achieve immediate and adequate ventilation. Even after the establishment of tracheostomy and artificial respiration sudden secretions may cause dangerous bouts of cyanosis. I should like to suggest in such cases the use of propranolol: a slow intravenous injection of 5 mg. may not only reduce the high pulse-rate but also avert the danger of ventricular fibrillation. In a similar case 8I have used propranolol to Sinclair, H. M. ibid. 1956, i, 381. Leren, P. Acta med. scand. 1966, 180, suppl. 466. Turpeinen, O., Miettinen, M., Karvonen, M. J., Roine, P., Pekkarinen, M., Lehtosuo, E. J., Alivirta, P. Am. J. clin. Nutr. 1968, 21, 255. 6. Crowley, W. J., Johns, T. R. Archs Neurol., Chicago, 1966, 14, 611. 7. Wills, J. H., McNamara, B. P., Fine, E. A. Fedn Proc. 1950, 9, 136. 8. Valero, A. Israel J. med. Sci. 1967, 3, 582.
4. 5.