857VITAMIN-E THERAPY

such dependence on exceptionally skilled attention.So many of the new treatments are of this type ;exsanguino-transfusion for acute leukaemia, support-ing transfusions for aplastic ansemia, the specialtechnique needed for nitrogen mustard administration-all these make great demands on the time ofdoctors that can hardly be met outside the specialteaching hospital clinic. In the U.S.A. it is appar-ently possible to entrust these repeated intravenousinfusions to the blood-bank nurse ; it is doubtful ifthis would be allowed here. And what of the almost

crippled haemophiliac who is given, for some months,a taste of normal life at the price of absolute depend-ence on the special clinic facilities ? 1 For if he missesone infusion his haemorrhages will recur. The

preparation alone of the special plasma needed every3 or 4 days must involve much labour. But similardifficulties were met, and solved, in the- treatmentof’diabetes and Addison’s disease ; and perhaps nowthat we know the site of the missing factor in haemo-philia further progress will lead to simpler methodsfor the continuous control of the coagulation defect

Vitamin-E TherapyVITAMIN E (tocopherol) was discovered some

twenty-five years ago during experiments on theeffect of dietary restriction on the breeding-power ofrats. Since that time many disorders not specificallyrelated to reproduction have been attributed to its

deficiency. In various animals these have includedmuscular dystrophy 1; brown pigmentation of the

uterus, skeletal muscles,2 and adipose tissues 3 ;exudative diathesis 4 ; encephalomalacia 5 ; renal abnor-malities 6; ceroid pigmentation of the liver 7; and theuneconomical use of protein and vitamin A. ’I Such

findings suggest that the vitamin has a wide sphereof activity, exerting its powerful anti-oxidant actionin many different biochemical systems.

Of vitamin E in man we know much less. Its

presence in human tissues can certainly be detectedby biological 10 and chemical 11 tests. There is evi-

dence, too, that during gestation it is transferredfrom the maternal circulation to the faetus.12 But

not- everyone agrees even that vitamin-E deficiencyis a significant cause of failure of reproduction-despite the encouraging first reports on habitualabortion. 13 Trials in muscular dystrophy and allied conditions have usually proved disappointing,14 thoughit should be remembered that its administration has

only limited success in dystrophic rats once thesehave become paralysed as the result of deficiency. 6The surprising claim of MiLHORAT and BARTELS 15that in human muscular disorders the absorption ofvitamin E is defective through its failure to conjugatewith inositol has not yet been confirmed. The hopethat vitamin-E medication may prove useful would

1. Olcott, H. S. J. Nutrit, 1938, 15, 221.2. Martin, A. J. P., Moore, T. Chem. Ind. 1936, 55, 236.3. Dam, H., Granados, H. Science, 1945, 102, 327.4. Dam, H., Glavind, J. Nature, Lond. 1938, 142, 1077.5. Dam, H., Glavind, J., Bernth, O., Hagens, E. Ibid, p. 1157.6. Martin, A. J. P., Moore, T. J. Hyg., Camb. 1939, 39, 643.7. Victor, J., Pappenheimer, A. M. J. exp. Med. 1945, 82, 375.8. Dam, H. Proc. Soc. exp. Biol. Med. 1944, 55, 55.9. Davies, A. W., Moore, T. Nature, Lond. 1941, 147, 794.

10. Evans, H. M., Burr, G. O. Mem. Univ. Calif. 1927, 8, 61.11. Emmerie, A., Engel, C. Rec. Tray. chim. Pays-Bas. 1939, 58, 895.12. Athanassiu, G. Klin. Wschr. 1947, p. 362.13. See Bacharach, A. L. Brit. med. J. 1940, i, 890.14. Fitzgerald, G., McArdle, B. Brain, 1941, 64, 19.15. Milhorat, A. T., Bartels, W. E. Science, 1945, 101, 93.

indeed have receded but for the faith of EvAN SHUTE,in Canada, who has had long experience in the treat-ment of both pregnant and non-pregnant patientswith wheat-germ oil concentrates and later synthetictocopherols. While his early investigations indicatedthat vitamin E might be beneficial in emergenciessuch as abruptio placentae 16 or premature labour,17he has concentrated latterlv on its use in cardiac andvascular diseases.18 From experience of 1500 casesof every type of heart disease he concludes thatvitamin E is both effective and safe ; that 80% ofcases improve continuously ; and that even in theworst cases the improvement may sometimes allowgreatly increased activity. These beneficial effects heascribes to the action of the vitamin in decreasingthe permeability and increasing the dilation of thecapillaries, in decreasing the anoxia of the cardiacmuscle, in preventing further thrombosis and resolvingexisting thrombi, and in softening and relaxing scartissue by invasion with fresh blood-vessels. He alsoclaims that for the same reasons the vitamin isvaluable in the treatment of indolent ulcers, arterio-sclerotic gangrene, thrombophlebitis and phlebo-thrombosis, cerebral thrombosis, thromboangiitisobliterans, purpura, and even defective powers ofvision and dark adaptation. Furthermore, BURGESS 19has found vitamin E effective in collagenoses such asatopic dermatitis, granulomatous ulceration of the

leg, sclerosis of the legs, and lupus erythematosus.On the other hand, other workers have been lesssuccessful in substantiating SHUTE’s claims. ThusMAKINSON et a1.,20 after comparing vitamin Ewith phenobarbitone, aminophylline, and calciumlactate in 22 cases of angina peetoris, concluded thatit has no value in this condition ; and BALL 21 was

equally unimpressed after tests on 10 cases. Similarlyin 13 cases of angina pectoris, and chronic heart-failure secondary to myocardial infarction or chronicrheumatic valvular disease, LEVY and BOAS 22 foundthat massive doses of 200-800 mg. daily were

ineffective, even when given for several weeks.Since SHUTE himself is not disturbed by the lack

of controls in his investigations, and even hints thatideas and controls may be incompatible, we mightwell hesitate before accepting all his conclusions,even if there were no contradictory results. At thesame time it is well to remember the conclusiveevidence from animal experiments that vitamin Edoes in fact participate both in maintaining thenormal permeability of capillaries and in protectingheart muscle from degeneration. Thus in expèri-ments with chicks DAM 4 found that deficiency ofvitamin E causes " exudative diathesis," charac-terised by an undue fragility of the capillaries with aresulting tendency to oedema. In the rat MASON 23found that partial deficiency of vitamin E causesvascular abnormalities of the foetus, with variabledegrees of dilation and thrombosis, haemorrhage, andsometimes oedema. In dogs with experimental kidneyinjuries HOLMAN 24 found that vitamin E prevents16. Shute, E. J. Obstet. Gynœc. 1937, 44, 121.17. Shute, E. Amer. J. Obstet. Gynec. 1942, 44, 271.18. Vogelsang, A., Shute, E., Shute, W. Med. Rec. 1948, 161, 83.19. Burgess, J. F. Lancet, Aug. 7, p. 215.20. Makinson, D. H., Oleesky, S., Stone, R. V. Ibid, 1948, i, 102.21. Ball, K. P. Ibid, p. 116.22. Levy, H., Boas, E. P. Ann. intern. Med. 1948, 28, 1117.23. Mason, K. E. Essays in Biology. Berkeley, 1943 ; p. 400.24. Holman, R. L. Proc. Soc. exp. Biol. Med. 1947, 66, 307.

858 PROCONSUL AFRICANUS

the development of arteritis. LAMBERT 25 is enthusi-astic over the value of the vitamin in the treatmentof aged dogs and cats suffering from heart disease.Cattle deficient in vitamin E, according to GULLIKSONand CALVERLEY,26 exhibit progressive electrocardio-graphic abnormalities, and are prone to suddendeath. MASON and EMMEL 27 have reported myo-cardial lesions in rats deprived of vitamin E for longperiods, while MooRE and his colleagues 6.28 holdthat the pigment granules found in the dystrophicmuscles of such animals strongly resemble those

typical of brown atrophy in the human heart. SHUTE’ssurprising claims for the therapeutic value of vitamin Etherefore become more plausible when all the knowneffects of experimental deficiency are considered.Further animal experimentation should indicate

clearly the directions in which controlled clinicaltests could profitably be undertaken.

For the present it is natural to ask whethervitamin E is deficient either in the average diet or in

25. Lambert, N. H. Vet. Rec. 1947, 59, 355. 26. Gullickson, T. W., Calverley, C. E. Science, 1946, 104,

312.27. Mason, K. E., Emmel, A. E. Anat. Rec. 1945, 92, 33. 28. Moore, T., Wang, Y. L. Brit. J. Nutrit. 1947, 1, 53.

that of patients suffering from diseases said to- respondto its administration. Clearly the doses said to benecessary for successful therapy are greatly in excessof those consumed in an ordinary diet. ThusBURGESS’S patients with collagenoses were havingdoses of 100-600 mg. daily, while their food containedonly the normal 15-30 mg. ; and he concludes thatdefective absorption or utilisation must be involved.SHUTE’ points out that the increased incidence of .

angina pectoris in America during recent years hascoincided with the milling of flour poor in vitamin E ;but he emphasises that his patients have derived nobenefit whatever from the vitamin in amounts equalto those found in ordinary diets, and he recommends200 mg. as an average daily dose for the controland maintenance of most patients with heart disease,with up to 900 mg. initially, provided that this heavierdosage is not contra-indicated by chronic rheumaticheart lesions or severe hypertension. He believesthat he is using vitamin E not as a food accessorybut as a chemotherapeutic agent. Indeed LEVY andBoAS have noticed that massive doses sometimescause headache and vertigo ; but the clinical significanceof these side-effects is still uncertain.

Annotations

THE KING’S HEALTH

ON Tuesday a bulletin from Buckingham Palaceannounced that the King is suffering from obstructionto the arterial circulation in the legs, and that thedefective blood-supply to the right foot causes anxiety.The bulletin, which is signed by Sir Maurice Cassidy,Sir Thomas Dunhill, Prof. J. R. Learmonth, Sir MortonSmart, and Sir John Weir, adds that " though His

Majesty’s general health, including the condition of hisheart, gives no reason for concern, there is no doubtthat the strain of the past 12 years has appreciablyaffected his resistance to physical fatigue." Accord-

ingly his visit to Australia and New Zealand, whichwas to begin on Jan. 27, has been cancelled; but he willcontinue to carry out his normal State duties at thePalace, including audiences.

Those who appreciate the weight of the physical andmental burden imposed on Royalty by a tour of thekind projected must be glad that this illness has declareditself now rather than later. Its seriousness is all tooevident, and is the more impressive because, in a lifeof service, the King has so seldom allowed himself tobe deflected from any public task, whether great or small.Yet there is good hope that, provided the acute phaseyields to rest and treatment, it will_ be followed by areturn of health and strength ; though possibly, like somany of his subjects at the same age, the King will haveto purchase continuing health at the cost of some ofhis more strenuous activities.

PROCONSUL AFRICANUS

ADDRESSING the Geological Society on Nov. 17Prof. W. E. Le Gros Clark, F.R.S., gave a short preliminaryaccount of the fossil skull of a Miocene ape recentlyfound on Rusinga Island in Kenya. The discovery wasmade by Mr. L. S. B. Leakev, PH.D., and Mrs. Leakeylast September, during the second season of the British-Kenya Miocene Expedition. Though a number of remainsof fossil Miocene apes have previously been found, notonly in Africa but elsewhere, these remains have hithertobeen almost entirely confined to teeth and fragments ofjaws. This is the first occasion on which a skull of oneof these early primates has been obtained.

The specimen belongs to a species Proconsul africanus,originally defined on the basis of the dentition by A. T.Hopwood of the British Museum. The greater part ofthe facial skeleton has been preserved-almost intacton the right side, but much crushed and distorted on theleft. The frontal region of the brain-case is also present,and the mandible is complete. The whole of the dentition(of which the third molars had already erupted andundergone some degree of wear) is excellently preserved.Portions of the occipital bone with the articular condyles,and also fragments of the petrosal bones, are amongisolated fragments which, because of lack of contacts,unfortunately cannot be placed with certainty in theirrelation to the main skull. From the general dimensionsof this skull, it appears that Proconsul africanus wassomewhat intermediate in size between a large gibbonand a small chimpanzee. It contrasts strongly with thechimpanzee and gorilla in the complete absence of a

supraorbital torus ; indeed, the supraorbital region hasa rather curiously human appearance. This latterfeature, however, does not necessarily betoken any specialrelationship with the Hominidæ, though it may perhapsbe taken to indicate that the latter have retained (orregained) certain primitive features which are of muchgreater antiquity than had been supposed. The skullis markedly prognathous ; but, as compared with themodern African apes, this may be partly illusory owingto the difference in the supraorbital prominence ; it mayalso to a slight degree be exaggerated by post-mortemdeformation. The contour of the nasal aperture resemblesthat of the catarrhine monkeys rather than the anthropoidapes, and in some endocranial features such as thepresence of a large subarcuate fossa (for the petrosallobule of the cerebellum), a broad vermiform fossa onthe occipital bone, and indications of a relatively smallfrontal lobe, it appears that the brain was more primitivethan that of the large apes of today. The whole skullis very lightly constructed, with a remarkably thincranial wall.The geological age of the deposits in which the specimen

was found is judged, mainly on palæontological evidence,to be Early Miocene. Since the Miocene period is generallybelieved to have begun about 3.5 million years ago, andto have ended 15 million years ago, the estimate of anantiquity of at least 20 million years is probably some-what conservative. Professor Le Gros Clark pointed, outthat, though this fossil skull is unique, it is only one of