833

their patients with paraesthesia only, the sensory symp-toms remitted only to recur within two to four months,with the onset of definite signs of subacute combined de-generation. Bethell and Sturgis14 also report that somejf their patients experienced definite relief of neurogenicmptoms while receiving folic acid. Meyer13 also notedsome symptomatic improvement in a few patients andreported that the combination of folic acid with subopti-mal doses of liver extract had a strikingly beneficialeffect in 3 cases of subacute combined degeneration.There is evidence therefore, to suggest that arguments

2 and 3 above could be modified to emphasise thathxmatological relapse occurs in addition to suboptimumremission and that mild transient neurological improve-ment may occur in addition to the much more florid

relapse, which is so well known.

EVIDENCE FOR SIMILAR METABOLIC MECHANISMS

I have implied above that the foundations of the con-cept of some fundamentally different metabolic problemm the nervous system are unsound and are open to a dif-ferent interpretation. There are, of course, divergencesthat need explanation such as the poor correlationbetween the haematological and neurological manifes-tations or relapses, but, as already pointed out, this is aproblem fundamental to many metabolic diseases whichinvolve the nervous system and I suggest that the answerlies not in some radically different function for vitaminB12 in the nervous system but is inherent in the very dif-ferent nature of the tissues involved, in this case theremarkable difference between the haemopoietic and ner-vous systems.Blood cells are regularly completely renewed within

weeks and months. This provides the haematologist withsome of the most promising therapeutic possibilities inclinical medicine, as exemplified by success in the treat-ment of leukaemias, as well as megaloblastic anaemias.The nervous system, however, is completely different.Neurons cease dividing in early life and metabolicallydamaged cells are therefore not replaced. Therapeuticpossibilities are accordingly severely limited. Further-more, the nervous system has developed its own specia-lised mechanisms, including blood-brain barrier

mechanisms, for maintaining its neuronal internal com-position and external environment against considerablemetabolic stress arising either within or outside the ner-vous system. It is these striking differences between thetwo tissues which probably account for the clinical

divergences in the hxmatological and neurological com-plications of vitamin-B deficiency (or other metabolicdiseases) discussed above.

If we accept the possibility that the metabolic basis ofnsmopoietic and nervous systems manifestations of vita-m1O-B12 deficiency are similar, does our present knowl-edge of the biochemical basis of megaloblast formation,bed any light on the mechanisms operating in the ner-’.ous system? The most widely favoured hypothesis is’hat vitamin-B12 deficiency interferes with the metabo-r;m or transport of folate.19-21 This might explain whydeficiency of either vitamin produces a similar haemato-jacal picture. I have reviewed elsewhere the neurologi-cal manifestations of folic-acid deficiency and have con-cluved that they are sometimes indistinguishable from.-.,se due to vitamin-B12 deficiency.22 Manzoor and :Jcle23 have described 10 patients with reversible

neurological disease due to folic-acid deficiency whichwas also indistinguishable from that due to vitamin-B12deficiency. I therefore suggest, that, as in the case ofmegaloblast formation, the neurological expression ofvitamin-B12 deficiency is due to a block in the metabo-lism of folic acid. In support of such a view it is of in-terest that patients with neurological complications ofvitamin-B12 deficiency have the highest serum-folatelevels.24 However, even if subsequent evidence revealsan entirely different mechanism for megaloblast forma-tion, the concept that the haematological and neurologi-cal expression of vitamin-B12 deficiency have a similarbiochemical basis would still be valid.

I am grateful to Dr 1. Chanarin and Prof. C. D. Marsden for helpfuldiscussion and advice.

Requests for reprints should be addressed to the University Depart-ment of Neurology, Institute of Psychiatry, De Crespigny Park, Lon-don SE5 8AF.

REFERENCES

1. Chanarin, I. The Megaloblastic Anæmias. Oxford, 1969.2. Brain, Walton, J. N. Brain’s Diseases of the Nervous System, London.

1969.3. Wilson, J., Langman, M. J. S. Nature, 1966, 212, 787.4. Cox, E. V., White, A. M. Lancet, 1962, ii, 853.5. Frenkel, E. P. J. clin. Invest. 1973, 52, 1237.6. Doig, R. K., Motteram, R., Robertson, E. G., Wood, I. J. Lancet, 1950, ii,

836.7. Jewesbury, E. C. O. ibid. 1954, ii, 307.8. Strachan, R. W., Henderson, J. G. Q. Jl. Med. 1965, 34, 303.9. Cox, E. V. in Vitamin B12 und Intrinsic Factor; 2 Europaisches Symposion.

(edited by H. Heinrich); p. 590. Stuttgart, 1962.10. Woltmann, H. W. Am. J. med. Sci. 1919, 157, 400.11. Ahrens, R. S. Archs Neurol. Psychiat., Chicago, 1932, 28, 92.12. Lockner, D., Reizenstein, P., Wennberg, P., Widden, L. Acta. hœmat. 1969,

41, 257.13. Meyer, L. M. Blood, 1947, 2, 50.14. Bethell, F. H., Sturgis, C. C. ibid. 1948, 3, 57.15. Schwartz, S. O., Kaplan, S. R., Armstrong, B. E. J. Lab. clin. Med. 1950,

35, 894.16. Will, J. J., Mueller, J. F., Brodine, C., Kiely, C. E., Friedman, B., Hawkins,

V. R., Dutra, I., Victor, R. W. ibid. 1959, 53, 22.17. Israëls, M. C. G., Wilkinson, J. F. Br. med. J. 1949, ii, 1072.18. Hall, B. E., Watkins, C. H. J. Lab. clin. Med. 1947, 32, 622.19. Chanarin, I. Lancet, 1973, ii, 538.20. Perry, J., Lumb, M., Laundy, M., Reynolds, E. H., Chanarin, I. Br. J.

Hœmat. 1976, 32, 243.21. Das, K. C., Herbert, V. Clins Hœmat. 1976, 5, 697.22. Reynolds, E. H. ibid. p. 661.23. Manzoor, M., Runcie, J. Br. med. J. 1976, ii, 1176.24. Waters, A. H., Mollin, D. L. J. clin. Path. 1961, 14, 335.

Reviews of Books

Scientific Foundadone of UrologyVol. I: Renal Disorders, Infections and Calculi. Edited by DAVIDINNES WILLIAMS, F.R.C.S., and GEOFFREY D. CHISHOLM, F.R.C.S.Institute of Urology, University of London. London: HeinemannMedical. 1976. Pp. 374. /;18.

IF you think it is cheating to use a dictionary when doinga crossword then you will have no use for this book, for clinicalclues and scientific solutions are the very reasons for its exis-tence. The first of two volumes, this one covers those aspectsof urology which have a nephrological flavour, and surgeonsare outnumbered by two to one among the contributors. Thebook reviews the present state of scientific understanding andanalysis upon which clinical progress, if not clinical practice,depends. The book rarely strays from its brief by duplicatingthe clinical textbook, and this reflects the skilful pruning by theeditors. Nearly all the information is available somewhere butnowhere else can it be so readily reached and so easily under-stood. Over a quarter of the book’s 400 large, double-columnpages are on stcne disease, a subject which lends itself to suchanalysis, and this section could well justify separate publica-tion. Chapters on epidemiology, crystallography, and physical

834

chemistry collate much widespread data, and the sections onthose awful twins, calcium metabolism and hyperparathy-roidism, are for once both comprehensive and yet comprehen-sible. The rare stones are covered in detail, and a little gem isthe short chapter on urinary calculi in bowel disorders. Renalfailure, renovascular hypertension, and transplantation are

dissected by physicians, surgeons, radiologists, and immunolo-gists without much squabbling. Obstructive nephropathyneeds more space; the single chapter does not waste a wordbut would benefit by being allowed to expand. Those who havebecome battle-weary in dealing with urinary infection will findtheir enthusiasm rejuvenated, and the chapter on antibioticconcentrations is an important contribution. Those yeasts,viruses, Mycoplasma, and parasites which stray into the uri-nary tract are all documented, and there is a modem look attuberculosis. The book continues through anatomy and gene-tics, physiology and prosthetics, covering an enormous amountof ground and it will be of value to a variety of people as wideas those who have written it. The editors regret omissions forreasons of space but perhaps they will allow sufficient hyper-plasia next time to include compensatory renal hypertrophy.Congratulations all round for a superb book which is uniquein the nephro-urological literature. At L 18 it is a bargain.

The Foot and its Disorders

Edited by LESLIE KLENERMAN, F.R.C.S., Northwick Park Hospi-tal, Harrow. Oxford: Blackwell. 1976. Pp. 239. /;8.50.

Mr Klenerman announces an intention to provide a succinctaccount of the present-day methods of clinical management offoot disorders, coupled with some aspects of the basic scientificadvances in the study of the foot. He has had the help of thir-teen other contributors, ranging from engineers and surgeonsto dermatologists and chiropodists. The book is aimed chieflyat the needs of the specialist orthopaedic surgeon and rheuma-tologist in training. The first two chapters, on the evolution ofthe foot and on functional anatomy, are interesting and givean excellent bibliography. They assume that the trainee has amuch wider basic knowledge of anatomy and is going to domore additional reading to supplement the text than is likely.Many would find the addition of simple line drawings of majortopographical anatomical points a help. The chapters on clini-cal problems vary considerably in length and detail of presen-tation. The long, full, and helpful chapter on hallux valgusand hallux rigidus contains many pages describing proceduresnot advocated. This space might be better devoted to expand-ing the short chapter on the foot in children, and particularlythe section on club foot. The sections on chiropody and onfootwear, particularly the section on chiropody, add to thevalue of a book which fulfils much of its aim. It is hoped thatfuture editions will be required and that the editor will be ableto obtain a greater uniformity of standard of contribution. Thequality of publication is high.

Persons at High Risk of CancerAn Approach to Cancer Etiology and Control. Edited by JOSEPHF. FRAUMENI, JR, National Cancer Institute, Bethesda, Maryland.New York and London: Academic. 1975. Pp. 544.$19, /;11.60.

REDUCTION in the incidence and mortality from cancer is

likely to be achieved more successfully as a result of preventionthan by treatment. The recognition of this conclusion stimu-lated the U.S. National Cancer Institute and the AmericanCancer Society to hold a conference in Key Biscayne, Florida,in December, 1974, on cancer risk factors. This book, whichforms the proceedings of that conference, is divided into sixsections. The first two, which occupy over half the book, aredevoted to host factors and environmental agents that eithercause or are associated with an increased risk of cancer. Therole of genetic factors and the association between cancer andacquired diseases are reviewed, and there are chapters on pre-malignant conditions and immune-deficiency diseases in rela-tion to cancer. A large variety of environmental agents can

cause cancer, and the proportion of all cancers that canattributed to such agents is considered to be as high as 8(jWhere the carcinogenic agent is known the implications forprevention are obvious, and there was agreement that no sir.

gle known measure would reduce the incidence or mortality ofcancer in men more than the elimination of cigarette smokingWhile the book shows that groups of people at high risk ofcancers of certain sites can be identified, it also makes it clearthat there is little evidence that early diagnosis and treatmen:can lead to improved survival. Professor MacMahon discussesthese limitations and points out the implication for researchThe third section deals with demographic factors associatedwith cancer frequency, and the fourth with practical oppor-tunities for prevention. The fifth section examines such topicsas the interaction of carcinogenic agents and how laboratontests can be used to investigate differences in the frequency ot’certain tumours. In a multi-author work such as this some

repetition is unavoidable. However, it contains useful tables

supported by comprehensive references which assemble infor-mation on cancer from many sources. People working in

cancer epidemiology will find it a valuable book.

Neoplasia in the Central Nervous SystemAdvances in Neurology: vol. XV. Edited by RICHARD A,THOMPSON, M.D., and JOHN R. GREEN, M.D. New York: Raven.1976.Pp.382.$35.

THIS book contains the proceedings of the second annualBarrow Neurological Institute symposium held in Phoenix,Arizona, in January, 1975. There are 22 chapters, and themain emphasis is on basic science applied to the biology ofbrain tumours. Excellent review articles are included on the

neuropathology of glioma and on virus or chemically inducedanimal brain tumours. There are also clinically orientedchapters concerned with advances in diagnostic methods, in-cluding computerised axial tomography for intracranialtumour. Chemotherapy and immunotherapy for glioma is de-scribed, with the presentation of some new data; there is a re-sponsible discussion of their place in management. Other

chapters review neuroansesthetic methods, microsurgery for

benign intracranial tumours, and the effects of systemic mahg-nancy on the nervous system. The object of the book is to bringthe clinical neurologist and neurosurgeon up to date both withbasic research in neuro-oncology and with advances in man-agement. This purpose is achieved, although a few of the excel-lent review chapters seem to lie outside this remit. The bookis copiously illustrated. It is recommended reading for all in-volved in the investigation or treatment of brain tumour.

Patterns of Sexuality and ReproductionALAN PARKES. London: Oxford University Press. 1976. Pp. 148.3.25, 1.50 (paperback).

Sir Alan Parkes, besides being an authority on reproductivebiology and scientific adviser to the world’s only turtle farm,is also a very entertaining speaker; and this little book is, as

we might expect, a delight to read. The first half deals with thephysiology of sexual maturation, sexual function, fertihu.pregnancy and lactation, and the mechanics of sex determma-tion and twinning. The rest considers social and environmentalinfluences on reproduction and sexual behaviour, such as thepossible reasons for seasonal variations in conception and birthrates (length of daylight, climate, and the "comfort factor",and merry-making at the traditional festive seasons), men-strual synchrony in girls’ dormitories, and sexual preference ir,relation to social dominance. An apparently light-heartedapproach belies the serious nature of the book, which is packedwith factual information, some of it derived from the authoi ·

own research. Even the slightly sensational notion that quair.of intercourse might affect the chances of conception could.says Sir Alan, have relevance to some cases of reduced feruL-ty-and this, he suggests, offers a fascinating (though perhapsdaunting) new area for research.