871
likely attributed to a specific central serotonergic effect of this compound. This beneficial effect of L-tryptophan also suggests that sufficient activity of L-tryptophan hydroxylase remained in the brain of these patients to convert a functionally significant portion of the administered L-tryptophan (via L-5-H.T.P.) to serotonin. From this, it may be inferred that the raphe nuclei which contain most of the brain serotonin-cell bodies-the latter being the site of synthesis of L-tryptophan hydroxylase-were either intact
most
or
Department of Medicine, University of the West Indies, Mona, Kingston 7,
Further studies will have to be done to elucidate these findings, which tend to associate central serotonergic mechanisms with the motor system.
JACQUES DELÉAN
Ministry of Health, Slipe Pen Road, Kingston 5, Jamaica.
J. C. RICHARDSON
StR,—The hypothesis of Mr Rivers and Mr Hassam (Oct. 4, 642) that cystic fibrosis (c.F.) is associated with a deficiency
of linoleic-acid
AUTOANTIBODY TESTS IN LIVER DISEASE SIR,-Autoantibody investigations are useful in the differential diagnosis of liver disease, but the interpretation of the results is not always easy, because there is considerable overlap between various conditions. Physicians may find the accompanying table useful in deciding the most probable diagnosis when one or more of the three
S. SIVA
ESSENTIAL-FATTY-ACID METABOLISM IN CYSTIC FIBROSIS p.
desaturase(s)
is based
on
the idea that arachi-
donic/linoleic-acid (20:4/18:2) ratios are lower in patients with c.F. than in those with "classical" essential-fatty-acid (E.F.A.)
deficiency. Unfortunately, in drawing this conclusion the authors have compared 42 patients with c.F. with only 1 patient with E.F.A. deficiency, and although this latter patient had apparently normal arachidonic-acid levels (and hence high 20:4/18:2) there are at least 5 patients in the literature with classical E.F.A. deficiency whose levels of arachidonic acid are so low as to be undetectable.1 2 Had Rivers and Hassam chosen these patients for comparison they would presumably have concluded that the 20:4/18:2 ratios in patients with c.F.
AUTOANTIBODY TESTS IN LIVER DISEASE TESTS POSITIVE
were
common tests-antinuclear factor, mitochondrial antibodies, and smooth-muscle antibody-are positive. The results have been calculated using Bayes’ formula’ on the incidence of the positive findings in the three conditions2 and the relative incidences of the diseases themselves.3 When there is a small number of conditions and a small number of tests the Bayesian calculation can be made in advance as it were, so that clinicians do not even have to use a desk calculator.
6 Friars Walk,
Exeter EX2 4AY.
S. I. TERRY
Jamaica
only partly degenerated.
Division of Neurology, Toronto General Hospital, 11 Norman Urquhart Wing, 101 College Street, Toronto, Canada M5G 1L7.
false-positive reactions (in syphilis). What methods did D’r Vranckx adopt to exclude such cases from the syphilis group? To determine the frequency of hepatic disease and hepatitisassociated antigenaemia in syphilis, patients with undoubted syphilitic infections must be studied. Such a definitive study is in progress in Jamaica.
G. H. HALL
HEPATITIS-B ANTIGEN AND SEROLOGICAL EVIDENCE OF SYPHILIS
SIR,-As the association between early syphilis and liver disease in adults is under debate,4 the letter by Dr Vranckx (May 24, p. 1193) is relevant, because he suggests his data show an association between the presence of hepatitis-B antigen and serological evidence of syphilis in blood-donors. He does not mention how syphilis was diagnosed, nor whether on follow-up any patients had clinical evidence of spirochaetal infection and, if so, at what stage of infection these patients
unusually high.
The point surely is that the 20:4/18:2 ratios in c.F. are normal or increased when compared with controls, and there is thus no reason to postulate a block in the conversion of 18:2 to 20:4. But the use of the ratio 20:4/18:2 is misleading since even a short period of fasting will lead to an increase in the ratio due to the faster turnover of 18:2, while extreme E.F.A. deficiency leads to a fall in the ratio, since 20:4 may disappear altogether whereas 18:2 is always detectable. If one simply quotes absolute values for the two fatty acids, the most obvious difference between patients with c.F. and those with E.F.A. deficiency is simply that the latter have much lower 18:2 levels. Thus, I believe that the difference between c.F. and E.F.A. deficiency is probably just one of degree. In an investigation of the effects of intestinal malabsorption on plasma-lipids, we compared the fatty-acid composition of the serum-lecithin of 23 patients with malabsorption from a variety of different causes3 and found similar changes irrespective of the underlying cause of the malabsorption. The only exception to this was that classical E.F.A. deficiency was found only in patients whose malabsorption was due to massive small-bowel resection.4 Why these patients should be particularly at risk is not altogether clear. But if they fail to absorb fat from their proximal small bowel (as occurs in E.F.A.-deficient rats’) there is no distal small bowel "in reserve". Furthermore the E.F.A.s of the biliary lecithin will not be reabsorbed, so that there will in effect be a continuous drain of the body’s E.F.A. stores in this situation. All other causes of malabsorption gave rise to changes identical to those found by other workers in c.F.: there is thus no reason to postulate an additional metabolic abnormality specific to c.. Why is there a discrepancy in the reported arachidonic-acid levels between different papers on E.F.A. deficiency? I believe
It is well recognised that acute viral infections, including A-associated hepatitis, are frequent causes of acute biologicallv
1. Caldwell, M. D., Jonsson, H. T., Othersen, H. B. J. Pediat. 1972, 81, 894. 2. Press, M., Hartop, P. J., Prottey, C. Lancet, 1974, i, 597. 3. Shimoyama, T., Kikuchi, H., Press, M., Thompson, G. R. Gut, 1973, 14, 716. 4. Press, M., Kikuchi, H., Shimoyama, T., Thompson, G. R. Br. med J. 1974,
1 Hall, G H. Lancet, 1967, ii, 555. 1 Irvine, W J. in Recent Advances in Clinical Pathology; series v, p. 507, 1968. 3 Knill-Jones, R. P. J. R. Coll. Phycns Lond. 1975, 9, 205. 4 Br med J. 1975, i,112.
5. Clark, S. B., Ekkers, T. E., Singh, A., Balint, J. A., Holt, P. R., Rodgers, J. B. J. Lipid Res. 1973, 14, 581. 6. Ackman, R. G. in Progress in the Chemistry of Fats and Other Lipids (edited by R. T. Holman); vol. 12. p. 165. Oxford, 1972.
were.
ii, 247.
872 that the
explanation may be technical. Polar stationary phases (such as DEGs) do not separate 20:4 from 22:1 or 20:3
likely attributed to a specific central serotonergic effect of this compound. This beneficial effect of L-tryptophan also suggests that sufficient activity of L-tryptophan hydroxylase remained in the brain of these patients to convert a functionally significant portion of the administered L-tryptophan (via L-5-H.T.P.) to serotonin. From this, it may be inferred that the raphe nuclei which contain most of the brain serotonin-cell bodies-the latter being the site of synthesis of L-tryptophan hydroxylase-were either intact
most
or
Department of Medicine, University of the West Indies, Mona, Kingston 7,
Further studies will have to be done to elucidate these findings, which tend to associate central serotonergic mechanisms with the motor system.
JACQUES DELÉAN
Ministry of Health, Slipe Pen Road, Kingston 5, Jamaica.
J. C. RICHARDSON
StR,—The hypothesis of Mr Rivers and Mr Hassam (Oct. 4, 642) that cystic fibrosis (c.F.) is associated with a deficiency
of linoleic-acid
AUTOANTIBODY TESTS IN LIVER DISEASE SIR,-Autoantibody investigations are useful in the differential diagnosis of liver disease, but the interpretation of the results is not always easy, because there is considerable overlap between various conditions. Physicians may find the accompanying table useful in deciding the most probable diagnosis when one or more of the three
S. SIVA
ESSENTIAL-FATTY-ACID METABOLISM IN CYSTIC FIBROSIS p.
desaturase(s)
is based
on
the idea that arachi-
donic/linoleic-acid (20:4/18:2) ratios are lower in patients with c.F. than in those with "classical" essential-fatty-acid (E.F.A.)
deficiency. Unfortunately, in drawing this conclusion the authors have compared 42 patients with c.F. with only 1 patient with E.F.A. deficiency, and although this latter patient had apparently normal arachidonic-acid levels (and hence high 20:4/18:2) there are at least 5 patients in the literature with classical E.F.A. deficiency whose levels of arachidonic acid are so low as to be undetectable.1 2 Had Rivers and Hassam chosen these patients for comparison they would presumably have concluded that the 20:4/18:2 ratios in patients with c.F.
AUTOANTIBODY TESTS IN LIVER DISEASE TESTS POSITIVE
were
common tests-antinuclear factor, mitochondrial antibodies, and smooth-muscle antibody-are positive. The results have been calculated using Bayes’ formula’ on the incidence of the positive findings in the three conditions2 and the relative incidences of the diseases themselves.3 When there is a small number of conditions and a small number of tests the Bayesian calculation can be made in advance as it were, so that clinicians do not even have to use a desk calculator.
6 Friars Walk,
Exeter EX2 4AY.
S. I. TERRY
Jamaica
only partly degenerated.
Division of Neurology, Toronto General Hospital, 11 Norman Urquhart Wing, 101 College Street, Toronto, Canada M5G 1L7.
false-positive reactions (in syphilis). What methods did D’r Vranckx adopt to exclude such cases from the syphilis group? To determine the frequency of hepatic disease and hepatitisassociated antigenaemia in syphilis, patients with undoubted syphilitic infections must be studied. Such a definitive study is in progress in Jamaica.
G. H. HALL
HEPATITIS-B ANTIGEN AND SEROLOGICAL EVIDENCE OF SYPHILIS
SIR,-As the association between early syphilis and liver disease in adults is under debate,4 the letter by Dr Vranckx (May 24, p. 1193) is relevant, because he suggests his data show an association between the presence of hepatitis-B antigen and serological evidence of syphilis in blood-donors. He does not mention how syphilis was diagnosed, nor whether on follow-up any patients had clinical evidence of spirochaetal infection and, if so, at what stage of infection these patients
unusually high.
The point surely is that the 20:4/18:2 ratios in c.F. are normal or increased when compared with controls, and there is thus no reason to postulate a block in the conversion of 18:2 to 20:4. But the use of the ratio 20:4/18:2 is misleading since even a short period of fasting will lead to an increase in the ratio due to the faster turnover of 18:2, while extreme E.F.A. deficiency leads to a fall in the ratio, since 20:4 may disappear altogether whereas 18:2 is always detectable. If one simply quotes absolute values for the two fatty acids, the most obvious difference between patients with c.F. and those with E.F.A. deficiency is simply that the latter have much lower 18:2 levels. Thus, I believe that the difference between c.F. and E.F.A. deficiency is probably just one of degree. In an investigation of the effects of intestinal malabsorption on plasma-lipids, we compared the fatty-acid composition of the serum-lecithin of 23 patients with malabsorption from a variety of different causes3 and found similar changes irrespective of the underlying cause of the malabsorption. The only exception to this was that classical E.F.A. deficiency was found only in patients whose malabsorption was due to massive small-bowel resection.4 Why these patients should be particularly at risk is not altogether clear. But if they fail to absorb fat from their proximal small bowel (as occurs in E.F.A.-deficient rats’) there is no distal small bowel "in reserve". Furthermore the E.F.A.s of the biliary lecithin will not be reabsorbed, so that there will in effect be a continuous drain of the body’s E.F.A. stores in this situation. All other causes of malabsorption gave rise to changes identical to those found by other workers in c.F.: there is thus no reason to postulate an additional metabolic abnormality specific to c.. Why is there a discrepancy in the reported arachidonic-acid levels between different papers on E.F.A. deficiency? I believe
It is well recognised that acute viral infections, including A-associated hepatitis, are frequent causes of acute biologicallv
1. Caldwell, M. D., Jonsson, H. T., Othersen, H. B. J. Pediat. 1972, 81, 894. 2. Press, M., Hartop, P. J., Prottey, C. Lancet, 1974, i, 597. 3. Shimoyama, T., Kikuchi, H., Press, M., Thompson, G. R. Gut, 1973, 14, 716. 4. Press, M., Kikuchi, H., Shimoyama, T., Thompson, G. R. Br. med J. 1974,
1 Hall, G H. Lancet, 1967, ii, 555. 1 Irvine, W J. in Recent Advances in Clinical Pathology; series v, p. 507, 1968. 3 Knill-Jones, R. P. J. R. Coll. Phycns Lond. 1975, 9, 205. 4 Br med J. 1975, i,112.
5. Clark, S. B., Ekkers, T. E., Singh, A., Balint, J. A., Holt, P. R., Rodgers, J. B. J. Lipid Res. 1973, 14, 581. 6. Ackman, R. G. in Progress in the Chemistry of Fats and Other Lipids (edited by R. T. Holman); vol. 12. p. 165. Oxford, 1972.
were.
ii, 247.
872 that the
explanation may be technical. Polar stationary phases (such as DEGs) do not separate 20:4 from 22:1 or 20:3
