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LINOLEIC ACID IN THE CHOLESTEROL ESTERS OF THE AORTIC WALL
877 that it might well indicate a chromosomal difference of some ldnd, but this cannot be haploidy of every nucleus in the syncytial form. That a majority of syncytial nuclei are haploid is, of course, possible, as Dr. Galton suggests, but it would not be right to ignore his distortion of Sohval et al. ; further, as it stands, it is in contradiction with facts as I have found them.23 It is also inaccurate of Dr. Galton to say that no account has been taken of the antigenic action of the placenta; done in 1959.4 Department of Pathology, Queen’s College, University of St. Andrews,
thiq
was
W. W. PARK.
Dundee.
INFANTILE STRUCTURAL SCOLIOSIS "
SIR,-Whilst in no way wishing to be stirred " into controversy by Mr. Denis Browne’s letter of March 26, I believe it important to consider a number of his points. It became apparent from
studying infants
scoliosis of unknown aetiology that there
with structural
were two
groups,
resolving and progressive.
The former, of which there have been 77, had a structural scoliosis which completely disappeared without treatment. There seems little point therefore in applying splintage. 60-70% of infants with such structural curves belong to this group. The progressive variety, usually (but not invariably) easily distinguished from the resolving, has not, in my experience, responded satisfactorily to any form of treatment, applied early or late. Mr. Denis Browne is incorrect in suggesting that we do not treat these children, but having abstracted those undergoing natural resolution, optimism concerning the effects of treatment is not substantiated by the results. Having seen well over 2000 patients in ten years I do not believe that" it is very rare ". Mr. Denis Browne suggests it is due to malposition in utero, as it may well be. However, in the whole series only 6 were noticed at birth and many not until the second or even third year. The progressive curves in these infants are in no way distinguishable from the typical idiopathic curves of the second decade. I think it erroneous to blame the intrauterine position for idiopathic curves in infants and ascribe a different cause to those occurring later. The Royal Infirmary, J. I. P. JAMES. Edinburgh.
LINOLEIC ACID IN THE CHOLESTEROL ESTERS OF THE AORTIC WALL a SIR,-In paper in your columns in 1958 we reportedIi that the percentage of saturated fatty acids in the cholesterol esters of the aortic wall decreases with increasing severity of atherosclerosis. Since then we have extended our analyses of the lipids of the arterial wall and the results will be published soon. One of the conclusions we can now draw with certainty is that the linoleic-acid percentage in the cholesterol-ester fatty acids (C.E.F.A.) increases considerably with atherosclerosis. Our present
values (determined by gas chromatography) are 245% for undiseased aortas and 37% for aortas with atheromas and/or plaques. mean
Sinclairmentioned " a chemical error that has been made in your columns on various occasions by distinguished fat chemists ". He pointed out that it has mistakenly been taken for granted that the octadecadienoic acid detected by gas chromatography is identical with linoleic acid, whereas it could equally well be a structural isomer of it. We have now established by ozonolysis and oxidation, followed by identification of the degradation products, that the double bonds of our octadecadienoic acid (isolated from the C.E.F.A. of atheromatous aortas by preparative gas chromatography) are in the same positions as in linoleic acid; infra-red analysis of the same sample (for which we are indebted to the Unilever Research 4. Park, W W. Ann. N.Y. Acad. Sci. 1959, 80, 152. 5. Bottcher, C. J. F., Keppler, J. G., ter Haar Romeny-Watchter, C. Boelsma-van Houte, E., van Gent, C. M. Lancet, 1958, ii, 1207. 6. Sinclair, H. M. ibid. 1959, ii, 789.
C.,
Laboratory, Vlaardingen, Holland) led to the conclusion that more than 98% of these bonds are cis-orientated. This proves that the octadecadienoic acid isolated from the cholesterol esters of the aortic wall is identical with linoleic acid. In the C.E.F.A. saturated acids (the mean total percentage of which decreases from 31 to 17%), the largest percentage decrease, relative to the value in undiseased aorta, is found for stearic acid. Since the two most striking changes in the c.E.F.A. are the increase of linoleic acid and the decrease of stearic acid, I would propose the ratio of linoleic acid to stearic acid as an index of the degree of atherosclerosis as reflected by the C.E.F.A. This index increased, in the preparations we have examined, from values between 2 and 7 for undiseased aortas to values between 15 and 35 for aortas with severe atherosclerosis. Physical Chemistry Laboratory, University of Leiden, Netherlands.
C. J. F. BÖTTCHER.
SERUM-LIPID STUDIES AND NICOTINIC-ACID THERAPY SIR,-For the past twelve months we have been using large doses of nicotinic acid (3-6 g. daily) in the treatment of patients with ischasmic heart-disease. Only patients with some clear abnormality of their blood-lipids have been included in our group of 25. We can confirm the favourable reports of Altschul et al.1 and Galbraith et al.2 and of other workers. With few exceptions patients have shown a reversal towards the normal lipid pattern. All the disorders were initially detected through a routine blood-lipid study. We can confirm that the side-effects of nicotinic acid have been transient and unimportant and are not We (like others) have not a serious drawback to treatment. noted any general development of tolerance to the drug, although twelve months cannot be considered a sufficient length of time to form any definite view on this point. Included in a full lipid study we do a routine lipid-tolerance We have confirmed that many patients with ischaemic heart-disease show an abnormal rise in total blood-lipids after the ingestion of 75 g. fat and that this reduced tolerance may be greatly improved following administration of nicotinic acid in large doses. This is in line with the work of Pomeranze et at3 who described an excessive and prolonged rise in total fat acids after a standard fatty meal in patients with arterial disease. They observed some improvement of fat tolerance in these patients when they were kept on a low fat intake. Our standard lipid-tolerance test is performed as follows:
test.
A specimen of blood is taken from the fasting patient. 75 g. of a synthetic fatty preparation (’ Prosparol ", Duncan, Flockhart) is then administered in a chocolate drink and further specimens of blood are taken at intervals of 2 and 4 hours. The patient is kept at rest before and during the test. Each specimen is examined for total lipids by Kunkel’s method 4the fasting specimen is also examined for total protein, lipoprotein pattern, and total serum-cholesterol. All specimens are examined for optical density, and a clearing test is performed after 4 hours by the intravenous injection of 300 units heparin, the final specimen being taken 15 minutes later.
In young healthy adults the lipid rise is rarely more than 100 mg. and never more than 150 mg. per 100 ml. In some patients the rise has been in excess of 150 mg. and has been This abnormally high rise as high as 600 mg. per 100 ml. appears to bear no close relation to the fasting total-lipid or serum-cholesterol levels. An abnormal lipid-tolerance test and/or deficient clearing may be the only unusual findings in this lipid study. We have not sufficient experience as yet to correlate lowered fat tolerance or deficient clearing with other abnormalities in blood-lipid behaviour; if indeed such a correlation exists at all. We would, however, suggest that a lipid-tolerance test might be useful in studies of patients suffering from coronary or peripheral 1. 2. 3. 4.
Altschul, R., Hoffer, A., Stephen, J. D. Arch. biochem. biophys. 1955 54, 588. Galbraith, R. A., Perry, W. F., Beamish, R. C. Lancet, 1959, i, 222. Pomeranze, J., Beinfield, W. H., Chessin, M. Circulation, 1954, 10, 742. Kunkel, H. G., Ahrens, E. H. Transactions of 7th Liver Injury Conference of Josiah Macy, Jr., Foundation. January, 1948.
thiq
was
W. W. PARK.
Dundee.
INFANTILE STRUCTURAL SCOLIOSIS "
SIR,-Whilst in no way wishing to be stirred " into controversy by Mr. Denis Browne’s letter of March 26, I believe it important to consider a number of his points. It became apparent from
studying infants
scoliosis of unknown aetiology that there
with structural
were two
groups,
resolving and progressive.
The former, of which there have been 77, had a structural scoliosis which completely disappeared without treatment. There seems little point therefore in applying splintage. 60-70% of infants with such structural curves belong to this group. The progressive variety, usually (but not invariably) easily distinguished from the resolving, has not, in my experience, responded satisfactorily to any form of treatment, applied early or late. Mr. Denis Browne is incorrect in suggesting that we do not treat these children, but having abstracted those undergoing natural resolution, optimism concerning the effects of treatment is not substantiated by the results. Having seen well over 2000 patients in ten years I do not believe that" it is very rare ". Mr. Denis Browne suggests it is due to malposition in utero, as it may well be. However, in the whole series only 6 were noticed at birth and many not until the second or even third year. The progressive curves in these infants are in no way distinguishable from the typical idiopathic curves of the second decade. I think it erroneous to blame the intrauterine position for idiopathic curves in infants and ascribe a different cause to those occurring later. The Royal Infirmary, J. I. P. JAMES. Edinburgh.
LINOLEIC ACID IN THE CHOLESTEROL ESTERS OF THE AORTIC WALL a SIR,-In paper in your columns in 1958 we reportedIi that the percentage of saturated fatty acids in the cholesterol esters of the aortic wall decreases with increasing severity of atherosclerosis. Since then we have extended our analyses of the lipids of the arterial wall and the results will be published soon. One of the conclusions we can now draw with certainty is that the linoleic-acid percentage in the cholesterol-ester fatty acids (C.E.F.A.) increases considerably with atherosclerosis. Our present
values (determined by gas chromatography) are 245% for undiseased aortas and 37% for aortas with atheromas and/or plaques. mean
Sinclairmentioned " a chemical error that has been made in your columns on various occasions by distinguished fat chemists ". He pointed out that it has mistakenly been taken for granted that the octadecadienoic acid detected by gas chromatography is identical with linoleic acid, whereas it could equally well be a structural isomer of it. We have now established by ozonolysis and oxidation, followed by identification of the degradation products, that the double bonds of our octadecadienoic acid (isolated from the C.E.F.A. of atheromatous aortas by preparative gas chromatography) are in the same positions as in linoleic acid; infra-red analysis of the same sample (for which we are indebted to the Unilever Research 4. Park, W W. Ann. N.Y. Acad. Sci. 1959, 80, 152. 5. Bottcher, C. J. F., Keppler, J. G., ter Haar Romeny-Watchter, C. Boelsma-van Houte, E., van Gent, C. M. Lancet, 1958, ii, 1207. 6. Sinclair, H. M. ibid. 1959, ii, 789.
C.,
Laboratory, Vlaardingen, Holland) led to the conclusion that more than 98% of these bonds are cis-orientated. This proves that the octadecadienoic acid isolated from the cholesterol esters of the aortic wall is identical with linoleic acid. In the C.E.F.A. saturated acids (the mean total percentage of which decreases from 31 to 17%), the largest percentage decrease, relative to the value in undiseased aorta, is found for stearic acid. Since the two most striking changes in the c.E.F.A. are the increase of linoleic acid and the decrease of stearic acid, I would propose the ratio of linoleic acid to stearic acid as an index of the degree of atherosclerosis as reflected by the C.E.F.A. This index increased, in the preparations we have examined, from values between 2 and 7 for undiseased aortas to values between 15 and 35 for aortas with severe atherosclerosis. Physical Chemistry Laboratory, University of Leiden, Netherlands.
C. J. F. BÖTTCHER.
SERUM-LIPID STUDIES AND NICOTINIC-ACID THERAPY SIR,-For the past twelve months we have been using large doses of nicotinic acid (3-6 g. daily) in the treatment of patients with ischasmic heart-disease. Only patients with some clear abnormality of their blood-lipids have been included in our group of 25. We can confirm the favourable reports of Altschul et al.1 and Galbraith et al.2 and of other workers. With few exceptions patients have shown a reversal towards the normal lipid pattern. All the disorders were initially detected through a routine blood-lipid study. We can confirm that the side-effects of nicotinic acid have been transient and unimportant and are not We (like others) have not a serious drawback to treatment. noted any general development of tolerance to the drug, although twelve months cannot be considered a sufficient length of time to form any definite view on this point. Included in a full lipid study we do a routine lipid-tolerance We have confirmed that many patients with ischaemic heart-disease show an abnormal rise in total blood-lipids after the ingestion of 75 g. fat and that this reduced tolerance may be greatly improved following administration of nicotinic acid in large doses. This is in line with the work of Pomeranze et at3 who described an excessive and prolonged rise in total fat acids after a standard fatty meal in patients with arterial disease. They observed some improvement of fat tolerance in these patients when they were kept on a low fat intake. Our standard lipid-tolerance test is performed as follows:
test.
A specimen of blood is taken from the fasting patient. 75 g. of a synthetic fatty preparation (’ Prosparol ", Duncan, Flockhart) is then administered in a chocolate drink and further specimens of blood are taken at intervals of 2 and 4 hours. The patient is kept at rest before and during the test. Each specimen is examined for total lipids by Kunkel’s method 4the fasting specimen is also examined for total protein, lipoprotein pattern, and total serum-cholesterol. All specimens are examined for optical density, and a clearing test is performed after 4 hours by the intravenous injection of 300 units heparin, the final specimen being taken 15 minutes later.
In young healthy adults the lipid rise is rarely more than 100 mg. and never more than 150 mg. per 100 ml. In some patients the rise has been in excess of 150 mg. and has been This abnormally high rise as high as 600 mg. per 100 ml. appears to bear no close relation to the fasting total-lipid or serum-cholesterol levels. An abnormal lipid-tolerance test and/or deficient clearing may be the only unusual findings in this lipid study. We have not sufficient experience as yet to correlate lowered fat tolerance or deficient clearing with other abnormalities in blood-lipid behaviour; if indeed such a correlation exists at all. We would, however, suggest that a lipid-tolerance test might be useful in studies of patients suffering from coronary or peripheral 1. 2. 3. 4.
Altschul, R., Hoffer, A., Stephen, J. D. Arch. biochem. biophys. 1955 54, 588. Galbraith, R. A., Perry, W. F., Beamish, R. C. Lancet, 1959, i, 222. Pomeranze, J., Beinfield, W. H., Chessin, M. Circulation, 1954, 10, 742. Kunkel, H. G., Ahrens, E. H. Transactions of 7th Liver Injury Conference of Josiah Macy, Jr., Foundation. January, 1948.