25
so it is not too surprising that the is often delayed or missed.2 In childhood diagnosis is characterised disease the by the appearance of ectatic in the vascular skin lesions bathing-trunk area, episodic pain most commonly affecting the limbs, and a subtle and symptomless corneal dystrophy. Abdominal pain may be mistaken for appendicitis. In adult males virtually no system is spared, with vascular disease of the kidneys, heart, and brain contributing to progressive disability. Vertigo with
protean and non-specific, correct
sensorineural hearing loss,3 arthropathy,4 and, rarely, lymphadenopathy5 are additional complications. Without dialysis or transplantation most affected males will succumb to renal failure by the age of 50. Treatment is far from satisfactory. Antiplatelet therapy may help to prevent the atherosclerotic and thromboembolic effects of damage to the vascular epithelium 36but experience of this approach is limited. The painful crises and constant burning acroparaesthesiae, which are probably caused by axonal neuropathy, are helped in many patients by phenytoin and/or carbamazepine, although carbamazepine may sometimes exacerbate autonomic dysfunction.7 Renal transplantation will correct renal function provided care is taken to ensure that the donor kidney does not originate from a heterozygote;8 transplantation may also prevent other disease manifestations by providing a source of normal enzyme for release into the circulation. However, a report of progressive cardiac involvement despite successful renal allotransplantation9 emphasises the importance of longterm follow-up studies. Rapid progress at the genetic level during the past few years means that genetic counselling should now be offered to all families in whom this condition has been diagnosed. Prenatal diagnosis based on enzyme assay in amniocytes and chorionic villi is well established.1O Carrier detection by use of conventional clinical and biochemical criteria is less reliable. A small proportion of carrier females are clinically affected and about 70% show signs of corneal dystrophy. Measurement of the a-galactosidase to 0-galactosidase activity ratio in leucocytes, plasma, fibroblasts, and hair follicles provides reasonable but not total discrimination between carriers and non-carriers." Consequently, localisation of the gene and subsequent identification of closely linked polymorphic DNA markers12 has been especially welcomed by the possible carriers in whom conventional testing has given equivocal results. This development was followed closely by isolation and characterisation of the a-galactosidase gene itself.13 The gene is about 12 kb
long and contains 7 exons encoding a protein of 429 aminoacids. The basic molecular defect has been studied in 130 patients and identified in 7, 5 of whom showed a partial deletion, 1 a duplication, and 1 a point mutation.14 Only the patient with the point mutation showed any residual a-galactosidase activity. The breakpoint junction for four of the five partial gene deletions was in an exon containing multiple Alu repeats, an observation consistent with the hypothesis that these may be hot spots for the generation of deletions and duplications as a consequence of misalignment and unequal crossing over in
precursor
meiosis. Demonstration of the basic molecular defect in a family with Anderson-Fabry disease is a major advance, not only for those scientists and clinicians with a keen interest in genotype-phenotype correlation, but also for close female relatives of patients who seek precise carrier detection. For
the patients themselves, who are sometimes driven to suicide by intractable pain and behavioural disturbance, identification and characterisation of the a-galactosidase gene greatly enhances short-term prospects for direct enzyme replacement and long-term hopes of somatic gene
therapy. 1. Desnick RJ, Bishop DF. Fabry disease: &agr;-galactosidase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease. 6th ed. New York: McGraw-Hill, 1989: 1751-96. 2. Morgan SH, Crawfurd M d’A. Anderson-Fabry disease. A commonly missed diagnosis. Br Med J 1988; 297: 872-73. 3. Morgan SH, Rudge P, Smith SJM, et al. The neurological complications of Anderson-Fabry disease (&agr;-galactosidase A deficiency)— investigation of symptomatic and presymptomatic patients. Q J Med 1990; 75: 491-504. 4. Sheth KJ, Bernhard GC. The arthropathy of Fabry disease. Arthritis Rheum 1979; 22: 781-83. 5. Mayou SC, Kirby JD, Morgan SH. Anderson-Fabry disease: an unusual presentation with lymphadenopathy. J R Soc Med 1989; 82: 555-56. 6. Sakuraba H, Igasrashi T, Shibata T, Suzuki Y. Effect of vitamin E and ticlopidine on platelet aggregation in Fabry’s disease. Clin Genet 1987; 31: 349-54. 7. Filling-Katz MR, Merrick HF, Fink JK, Miles RB, Sokol J, Barton NW. Carbamazepine in Fabry’s disease: effective analgesia with dosedependent exacerbation of autonomic dysfunction. Neurology 1989; 39: 598-600. 8. Popli S, Molnar ZV, Leehey DJ, et al. Involvement of renal allograft by Fabry’s disease. Am J Nephrol 1987; 7: 316-18. 9. Kramer W, Thormann J, Mueller K, Frenzel H. Progressive cardiac involvement by Fabry’s disease despite successful renal allotransplantation. Int J Cardiol 1985; 7: 72-75. 10. Kleijer WJ, Hussaarts-Odijk LM, Sachs ES, Jahoda MGJ, Niermeijer MF. Prenatal diagnosis of Fabry’s disease by direct analysis of chorionic villi. Prenat Diagn 1987; 7: 283-87. 11. Spence MW, Goldbloom AL, Burgess JK, D’Entremont D, Ripley BA, Weldon KL. Heterozygote detection in angiokeratoma corporis diffusum (Anderson-Fabry disease) J Med Genet 1977; 14: 91-99. 12. MacDermot KD, Morgan SH, Cheshire JK, Wilson TM. AndersonFabry disease, a close linkage with highly polymorphic DNA markers DXS17, DXS87 and DXS88. Hum Genet 1987; 77: 263-66. 13. Bishop DF, Calhoun DH, Bernstein HS, Hantsopoulos P, Quinn M, Desnick RJ. Human &agr;-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. Proc Natl Acad Sci 1986; 83: 4859-63. 14. Bernstein HS, Bishop DF, Astrin KH, et al. Fabry disease: six gene rearrangements and an exonic point mutation in the &agr;-galactosidase gene. J Clin Invest 1989; 83: 1390-99.
LIPIDS AND MULTIPLE SCLEROSIS In this issue (p 37) we publish a paper by Dr R. L. Swank that marks forty years of study into the relation between dietary fat and the prevalence of multiple sclerosis (MS). Some essential questions remain. Is there a relation? What is the mechanism? Does dietary modification confer any
benefit? The initial suggestion of a link between MS and diet was made on the basis of epidemiology / elaborated by analogy,22 and received support from subsequent epidemiological studies during the next twenty years.3 Coincidental evidence of a possible relation between polyunsaturated fatty acids and MS was provided by the observation that the
proportions of the omega-6 fatty acids (arachidonic and linoleic acids) in the lecithin fraction of cerebral myelin differed in MS patients from those in normal controls 4 This suggestion of a lipid abnormality of MS was strengthened by subsequent reports of low levels of linoleic acid in patients’ serum, platelets, and red cells.5-7 Although these observations have been reproduceds,9 they have not been found consistently and some workers have suggested that they are merely a feature of chronic neurological disease.10,11
26
Nevertheless, on the basis of this epidemiological and biochemical evidence several clinical trials, some blind and controlled and others open and uncontrolled, have been conducted and considerable advice about dietary modification has been given to patients by self-help groups and through commercial advertising. Most of the evidence has related to the omega-6 group of polyunsaturated fatty acids, which are found in sunflower seed oil and oil of evening primrose, rather than the omega-3 acids, such as docosahexanoic acid and eicosapentanoic acid, which are found in fish body oil. The facts are few: studies relating to omega-6 polyunsaturated fatty acids include two doubleblind controlled clinical trials that showed a statistically significant reduction in attack severity in patients taking lineolic acid supplements12,13 and one that did not;14 a re-analysis of patients in all three trials showed a statistically significant reduction in disease progression in treated patients;15 and with respect to omega-3 fatty acids, a large controlled clinical trial showed a trend towards benefit in the treated group that did not reach statistical significance.16 Several studies that were uncontrolled or that used, as does Swank, patients who default from treatment as controls to compare with those who remain on treatment, have reported benefit for patients who limited their dietary saturated fatty acid intake and supplemented this diet with polyunsaturates.17,1S The difficulty with such assessments is that patients who are well are more likely to continue on treatment than those who deteriorate, so "good compliers" and "bad compliers" are likely to be self-selected from those who do well and those who do badly, giving the predictable "positive" result.
Despite the lack of firm evidence, many patients with MS modify their diet to reduce the intake of saturated fatty acid and to increase the quantity of polyunsaturates. Many patients achieve this goal by simple dietary modification and increase the intake of linoleic acid, as an omega-6 group acid, and the fish body oils, as omega-3 acids. In addition, many patients supplement their diet with capsules of sunflower oil, which is predominantly linoleic acid, oil of evening primrose, which contains linoleic acid and gamma linolenic acid, and docosahexanoic acids of the omega-3 series. Yet no now
controlled clinical trial has shown a benefit from the use of gamma-linolenic acid and none has shown more than a trend towards benefit with the fish body oils. The change in dietary habits during the past 40 years suggests that confirmation of the original hypothesis-that people consuming high saturated fat diets are more liable to manifest multiple sclerosis-may never be achieved. The original data on lipid variation in diet and tissues of MS patients were assumed to represent abnormalities in the cell membrane and therefore specifically the myelin. It is now recognised that the possible role of these lipids is extensive and, if dietary lipids are relevant to MS, it may be via a role in the structure of myelin, the formation of prostanoids and therefore on immune function, or on platelet and erythrocyte stickiness and therefore on the microcirculation. Before further necessarily large, and ideally controlled and blind, studies of lipid supplementation in MS are undertaken more needs to be understood at a biochemical level about the possible role of these lipids in the disease and the effect of manipulations of intake. The advent of magnetic resonance imaging as a method of monitoring the development of cerebral lesions and therefore of assessing the rates of attack in MS might be a more rapid way to assess the effectiveness of putative therapy and thereby provide a
method of demonstrating, on a reasonably short time scale, whether dietary supplementation with polyunsaturated fatty acids or restriction of other lipids has a genuine and reproducible beneficial effect upon the disease. Until such a definitive trial is undertaken the role of lipids in MS must remain not proven. 1. Swank RL. Multiple sclerosis: a correlation of its incidence with dietary fat. Am J Med Sci 1950; 220: 421-30. 2. Sinclair HM. Deficiency of essential fatty adds and atherosclerosis etcetera. Lancet 1956; i: 381-83. 3. Alter M, Yamoor M, Harshe M. Multiple sclerosis and nutrition. Arch Neurol 1974; 31: 267-72. 4. Baker RWR, Thompson RHS, Zilkha KJ. Fatty acid composition of brain lecithins in multiple sclerosis. Lancet 1963; 1: 26-27. 5. Baker RWR, Thompson RHS, Zilkha KJ. Serum fatty acids in multiple sclerosis. J Neurol Neurosurg Psychiatry 1964; 27: 408-14. 6. Baker RWR, Thompson RHS, Zilkha KJ. Serum cholesterol linoleate levels in multiple sclerosis. J Neurol Neurosurg Psychiatry 1966; 29: 95-98. 7. Gul S, Smith AD, Thompson RHS, Payling-Wright H, Zilkha KJ. Fatty acid composition of phospholipids from platelets and erythrocytes in multiple sclerosis. J Neurol Neurosurg Psychiatry 1970; 33: 506-10. 8. Tichy J, Vymazel J, Michaelec C. Serum lipoproteins, cholesterol esters and phospholipids in multiple sclerosis. Acta Neurol Scand 1969; 45: 32-40. 9. Neu IS. Essential fatty adds in serum and cerebrospinal fluid of multiple sclerosis patients. Acta Neurol Scand 1983; 67: 151-63. 10. Love WC, Reynolds M, Cashel A, Callaghan N. Linoleate and fatty acid patterns of serum lipids in multiple sclerosis and other diseases. Biochem Soc Trans 1973; 1: 141-43. 11. Wolfgram F, Myers L, Ellison G, Kinprath W. Serum linoleic add in multiple sclerosis. Neurology 1975; 25: 768-86. 12. Millar JHD, Zilkha KJ, Langman MJS, et al. Double blind trial of linoleate supplementation of the diet in multiple sclerosis. Br Med J 1973; i: 765-68. 13. Bates D, Fawcett PRW, Shaw DA, Weightman D. Polyunsaturated fatty adds in the treatment of acute remitting multiple sclerosis. Br Med J
1978; 2: 1390-91. 14.
15.
Paty DW, Cousin HK, Reid S, Adlakha K. Lineolic acid in multiple sclerosis: Failure to show any therapeutic benefit. Acta Neurol Scand 1978; 58: 53-58. Dworkin RH, Bates D, Millar JHD, Paty DW. Linoleic add and multiple sclerosis: a re-analysis of three double blind trials. Neurology 1984; 34:
1441-45. 16. Bates D, Cartlidge NEF, French JM, et al. A double-blind controlled trial of long chain n-3 polyunsaturated fatty adds in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 1989; 52: 18-22. 17. Swank RL. Multiple sclerosis: Twenty years on a low fat diet. Arch Neurol 1970; 23: 460-74. 18. Fitzgerald G, Harbige LS, Forti A, Crawford MA. The effect of nutritional counselling on diet and plasma EFA status in multiple sclerosis patients over three years. Human Nutr Appl Nutr 1987; 41a: 297-310.
Publishers’announcement New editor of The Lancet We
announce today the appointment of Robin Fox as the 11 th editor of The Lancet. Having qualified in medicine at the University of Edinburgh in 1965, Robin Fox was originally lured into medical journalism by Ian Douglas-Wilson, the paper’s 8th
editor. The son of Sir Theodore Fox (editor 1944-64), he has been-with David Sharp-a deputy editor of The Lancet since 1976.
so it is not too surprising that the is often delayed or missed.2 In childhood diagnosis is characterised disease the by the appearance of ectatic in the vascular skin lesions bathing-trunk area, episodic pain most commonly affecting the limbs, and a subtle and symptomless corneal dystrophy. Abdominal pain may be mistaken for appendicitis. In adult males virtually no system is spared, with vascular disease of the kidneys, heart, and brain contributing to progressive disability. Vertigo with
protean and non-specific, correct
sensorineural hearing loss,3 arthropathy,4 and, rarely, lymphadenopathy5 are additional complications. Without dialysis or transplantation most affected males will succumb to renal failure by the age of 50. Treatment is far from satisfactory. Antiplatelet therapy may help to prevent the atherosclerotic and thromboembolic effects of damage to the vascular epithelium 36but experience of this approach is limited. The painful crises and constant burning acroparaesthesiae, which are probably caused by axonal neuropathy, are helped in many patients by phenytoin and/or carbamazepine, although carbamazepine may sometimes exacerbate autonomic dysfunction.7 Renal transplantation will correct renal function provided care is taken to ensure that the donor kidney does not originate from a heterozygote;8 transplantation may also prevent other disease manifestations by providing a source of normal enzyme for release into the circulation. However, a report of progressive cardiac involvement despite successful renal allotransplantation9 emphasises the importance of longterm follow-up studies. Rapid progress at the genetic level during the past few years means that genetic counselling should now be offered to all families in whom this condition has been diagnosed. Prenatal diagnosis based on enzyme assay in amniocytes and chorionic villi is well established.1O Carrier detection by use of conventional clinical and biochemical criteria is less reliable. A small proportion of carrier females are clinically affected and about 70% show signs of corneal dystrophy. Measurement of the a-galactosidase to 0-galactosidase activity ratio in leucocytes, plasma, fibroblasts, and hair follicles provides reasonable but not total discrimination between carriers and non-carriers." Consequently, localisation of the gene and subsequent identification of closely linked polymorphic DNA markers12 has been especially welcomed by the possible carriers in whom conventional testing has given equivocal results. This development was followed closely by isolation and characterisation of the a-galactosidase gene itself.13 The gene is about 12 kb
long and contains 7 exons encoding a protein of 429 aminoacids. The basic molecular defect has been studied in 130 patients and identified in 7, 5 of whom showed a partial deletion, 1 a duplication, and 1 a point mutation.14 Only the patient with the point mutation showed any residual a-galactosidase activity. The breakpoint junction for four of the five partial gene deletions was in an exon containing multiple Alu repeats, an observation consistent with the hypothesis that these may be hot spots for the generation of deletions and duplications as a consequence of misalignment and unequal crossing over in
precursor
meiosis. Demonstration of the basic molecular defect in a family with Anderson-Fabry disease is a major advance, not only for those scientists and clinicians with a keen interest in genotype-phenotype correlation, but also for close female relatives of patients who seek precise carrier detection. For
the patients themselves, who are sometimes driven to suicide by intractable pain and behavioural disturbance, identification and characterisation of the a-galactosidase gene greatly enhances short-term prospects for direct enzyme replacement and long-term hopes of somatic gene
therapy. 1. Desnick RJ, Bishop DF. Fabry disease: &agr;-galactosidase deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic basis of inherited disease. 6th ed. New York: McGraw-Hill, 1989: 1751-96. 2. Morgan SH, Crawfurd M d’A. Anderson-Fabry disease. A commonly missed diagnosis. Br Med J 1988; 297: 872-73. 3. Morgan SH, Rudge P, Smith SJM, et al. The neurological complications of Anderson-Fabry disease (&agr;-galactosidase A deficiency)— investigation of symptomatic and presymptomatic patients. Q J Med 1990; 75: 491-504. 4. Sheth KJ, Bernhard GC. The arthropathy of Fabry disease. Arthritis Rheum 1979; 22: 781-83. 5. Mayou SC, Kirby JD, Morgan SH. Anderson-Fabry disease: an unusual presentation with lymphadenopathy. J R Soc Med 1989; 82: 555-56. 6. Sakuraba H, Igasrashi T, Shibata T, Suzuki Y. Effect of vitamin E and ticlopidine on platelet aggregation in Fabry’s disease. Clin Genet 1987; 31: 349-54. 7. Filling-Katz MR, Merrick HF, Fink JK, Miles RB, Sokol J, Barton NW. Carbamazepine in Fabry’s disease: effective analgesia with dosedependent exacerbation of autonomic dysfunction. Neurology 1989; 39: 598-600. 8. Popli S, Molnar ZV, Leehey DJ, et al. Involvement of renal allograft by Fabry’s disease. Am J Nephrol 1987; 7: 316-18. 9. Kramer W, Thormann J, Mueller K, Frenzel H. Progressive cardiac involvement by Fabry’s disease despite successful renal allotransplantation. Int J Cardiol 1985; 7: 72-75. 10. Kleijer WJ, Hussaarts-Odijk LM, Sachs ES, Jahoda MGJ, Niermeijer MF. Prenatal diagnosis of Fabry’s disease by direct analysis of chorionic villi. Prenat Diagn 1987; 7: 283-87. 11. Spence MW, Goldbloom AL, Burgess JK, D’Entremont D, Ripley BA, Weldon KL. Heterozygote detection in angiokeratoma corporis diffusum (Anderson-Fabry disease) J Med Genet 1977; 14: 91-99. 12. MacDermot KD, Morgan SH, Cheshire JK, Wilson TM. AndersonFabry disease, a close linkage with highly polymorphic DNA markers DXS17, DXS87 and DXS88. Hum Genet 1987; 77: 263-66. 13. Bishop DF, Calhoun DH, Bernstein HS, Hantsopoulos P, Quinn M, Desnick RJ. Human &agr;-galactosidase A: nucleotide sequence of a cDNA clone encoding the mature enzyme. Proc Natl Acad Sci 1986; 83: 4859-63. 14. Bernstein HS, Bishop DF, Astrin KH, et al. Fabry disease: six gene rearrangements and an exonic point mutation in the &agr;-galactosidase gene. J Clin Invest 1989; 83: 1390-99.
LIPIDS AND MULTIPLE SCLEROSIS In this issue (p 37) we publish a paper by Dr R. L. Swank that marks forty years of study into the relation between dietary fat and the prevalence of multiple sclerosis (MS). Some essential questions remain. Is there a relation? What is the mechanism? Does dietary modification confer any
benefit? The initial suggestion of a link between MS and diet was made on the basis of epidemiology / elaborated by analogy,22 and received support from subsequent epidemiological studies during the next twenty years.3 Coincidental evidence of a possible relation between polyunsaturated fatty acids and MS was provided by the observation that the
proportions of the omega-6 fatty acids (arachidonic and linoleic acids) in the lecithin fraction of cerebral myelin differed in MS patients from those in normal controls 4 This suggestion of a lipid abnormality of MS was strengthened by subsequent reports of low levels of linoleic acid in patients’ serum, platelets, and red cells.5-7 Although these observations have been reproduceds,9 they have not been found consistently and some workers have suggested that they are merely a feature of chronic neurological disease.10,11
26
Nevertheless, on the basis of this epidemiological and biochemical evidence several clinical trials, some blind and controlled and others open and uncontrolled, have been conducted and considerable advice about dietary modification has been given to patients by self-help groups and through commercial advertising. Most of the evidence has related to the omega-6 group of polyunsaturated fatty acids, which are found in sunflower seed oil and oil of evening primrose, rather than the omega-3 acids, such as docosahexanoic acid and eicosapentanoic acid, which are found in fish body oil. The facts are few: studies relating to omega-6 polyunsaturated fatty acids include two doubleblind controlled clinical trials that showed a statistically significant reduction in attack severity in patients taking lineolic acid supplements12,13 and one that did not;14 a re-analysis of patients in all three trials showed a statistically significant reduction in disease progression in treated patients;15 and with respect to omega-3 fatty acids, a large controlled clinical trial showed a trend towards benefit in the treated group that did not reach statistical significance.16 Several studies that were uncontrolled or that used, as does Swank, patients who default from treatment as controls to compare with those who remain on treatment, have reported benefit for patients who limited their dietary saturated fatty acid intake and supplemented this diet with polyunsaturates.17,1S The difficulty with such assessments is that patients who are well are more likely to continue on treatment than those who deteriorate, so "good compliers" and "bad compliers" are likely to be self-selected from those who do well and those who do badly, giving the predictable "positive" result.
Despite the lack of firm evidence, many patients with MS modify their diet to reduce the intake of saturated fatty acid and to increase the quantity of polyunsaturates. Many patients achieve this goal by simple dietary modification and increase the intake of linoleic acid, as an omega-6 group acid, and the fish body oils, as omega-3 acids. In addition, many patients supplement their diet with capsules of sunflower oil, which is predominantly linoleic acid, oil of evening primrose, which contains linoleic acid and gamma linolenic acid, and docosahexanoic acids of the omega-3 series. Yet no now
controlled clinical trial has shown a benefit from the use of gamma-linolenic acid and none has shown more than a trend towards benefit with the fish body oils. The change in dietary habits during the past 40 years suggests that confirmation of the original hypothesis-that people consuming high saturated fat diets are more liable to manifest multiple sclerosis-may never be achieved. The original data on lipid variation in diet and tissues of MS patients were assumed to represent abnormalities in the cell membrane and therefore specifically the myelin. It is now recognised that the possible role of these lipids is extensive and, if dietary lipids are relevant to MS, it may be via a role in the structure of myelin, the formation of prostanoids and therefore on immune function, or on platelet and erythrocyte stickiness and therefore on the microcirculation. Before further necessarily large, and ideally controlled and blind, studies of lipid supplementation in MS are undertaken more needs to be understood at a biochemical level about the possible role of these lipids in the disease and the effect of manipulations of intake. The advent of magnetic resonance imaging as a method of monitoring the development of cerebral lesions and therefore of assessing the rates of attack in MS might be a more rapid way to assess the effectiveness of putative therapy and thereby provide a
method of demonstrating, on a reasonably short time scale, whether dietary supplementation with polyunsaturated fatty acids or restriction of other lipids has a genuine and reproducible beneficial effect upon the disease. Until such a definitive trial is undertaken the role of lipids in MS must remain not proven. 1. Swank RL. Multiple sclerosis: a correlation of its incidence with dietary fat. Am J Med Sci 1950; 220: 421-30. 2. Sinclair HM. Deficiency of essential fatty adds and atherosclerosis etcetera. Lancet 1956; i: 381-83. 3. Alter M, Yamoor M, Harshe M. Multiple sclerosis and nutrition. Arch Neurol 1974; 31: 267-72. 4. Baker RWR, Thompson RHS, Zilkha KJ. Fatty acid composition of brain lecithins in multiple sclerosis. Lancet 1963; 1: 26-27. 5. Baker RWR, Thompson RHS, Zilkha KJ. Serum fatty acids in multiple sclerosis. J Neurol Neurosurg Psychiatry 1964; 27: 408-14. 6. Baker RWR, Thompson RHS, Zilkha KJ. Serum cholesterol linoleate levels in multiple sclerosis. J Neurol Neurosurg Psychiatry 1966; 29: 95-98. 7. Gul S, Smith AD, Thompson RHS, Payling-Wright H, Zilkha KJ. Fatty acid composition of phospholipids from platelets and erythrocytes in multiple sclerosis. J Neurol Neurosurg Psychiatry 1970; 33: 506-10. 8. Tichy J, Vymazel J, Michaelec C. Serum lipoproteins, cholesterol esters and phospholipids in multiple sclerosis. Acta Neurol Scand 1969; 45: 32-40. 9. Neu IS. Essential fatty adds in serum and cerebrospinal fluid of multiple sclerosis patients. Acta Neurol Scand 1983; 67: 151-63. 10. Love WC, Reynolds M, Cashel A, Callaghan N. Linoleate and fatty acid patterns of serum lipids in multiple sclerosis and other diseases. Biochem Soc Trans 1973; 1: 141-43. 11. Wolfgram F, Myers L, Ellison G, Kinprath W. Serum linoleic add in multiple sclerosis. Neurology 1975; 25: 768-86. 12. Millar JHD, Zilkha KJ, Langman MJS, et al. Double blind trial of linoleate supplementation of the diet in multiple sclerosis. Br Med J 1973; i: 765-68. 13. Bates D, Fawcett PRW, Shaw DA, Weightman D. Polyunsaturated fatty adds in the treatment of acute remitting multiple sclerosis. Br Med J
1978; 2: 1390-91. 14.
15.
Paty DW, Cousin HK, Reid S, Adlakha K. Lineolic acid in multiple sclerosis: Failure to show any therapeutic benefit. Acta Neurol Scand 1978; 58: 53-58. Dworkin RH, Bates D, Millar JHD, Paty DW. Linoleic add and multiple sclerosis: a re-analysis of three double blind trials. Neurology 1984; 34:
1441-45. 16. Bates D, Cartlidge NEF, French JM, et al. A double-blind controlled trial of long chain n-3 polyunsaturated fatty adds in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 1989; 52: 18-22. 17. Swank RL. Multiple sclerosis: Twenty years on a low fat diet. Arch Neurol 1970; 23: 460-74. 18. Fitzgerald G, Harbige LS, Forti A, Crawford MA. The effect of nutritional counselling on diet and plasma EFA status in multiple sclerosis patients over three years. Human Nutr Appl Nutr 1987; 41a: 297-310.
Publishers’announcement New editor of The Lancet We
announce today the appointment of Robin Fox as the 11 th editor of The Lancet. Having qualified in medicine at the University of Edinburgh in 1965, Robin Fox was originally lured into medical journalism by Ian Douglas-Wilson, the paper’s 8th
editor. The son of Sir Theodore Fox (editor 1944-64), he has been-with David Sharp-a deputy editor of The Lancet since 1976.
