147

and before the increase in glycerol release, an effect whichwas inhibited by dinitrophenol, suggesting that the calciumreleased came from an intracellular pool. After perfusionof the cells with insulin (100 JLU per ml.), the subsequentaddition of adrenaline induced only slight lipolysis and 45Caefflux. These results suggest that in addition to itsmobilisation of calcium from membrane stores, insulininhibits the release of calcium from the intracellular poolsand thus would favour a rise in intracellular free calciumconcentration.

The data reviewed provide the basis for a hypothesisabout the mode of insulin action by a mechanism in-dependent of its effects on tissue CA.M.P. In this modelthe binding of insulin to its specific receptors producesa change in the conformation in the plasma membrane,resulting in displacement of calcium from high-affinitybinding sites on the plasma membrane and/or theendoplasmic reticulum together with inhibition ofCa++ release from intracellular pools, resulting in anincrease in cytoplasmic free calcium. The increase in

cytoplasmic free calcium inhibits the cA.M.p.-dependentprotein kinase and activates the adipose-tissue phospho-protein phosphatase, so resulting in the inhibition oftriglyceride lipase and glycogen phosphorylase andstimulating glycogen synthetase. Such changes in theactivities of cytosol enzymes would inhibit lipolysisand glycogenolysis, and stimulate glycogenesis. Asimultaneous increase in mitochondrial calcium in

response to the rise in cytoplasmic level would activatepyruvate dehydrogenase and so stimulate lipogenesis.In this way, calcium ions might provide the intra-cellular second messenger for insulin action, while thedisplacement of Ca++ from the plasma membraneenhances the transport of substrates as well as ions.This hypothesis offers a unitary theory explaining boththe membrane and intracellular effects of insulin.

Requests for reprints should be addressed to B. R. T.

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F. L., Walsh, D. A., Krebs, E. G. ibid. 1970, 245, 6317.16. Walsh, D. A., Ashby, D., Gonzales, C., Clarkins, D., Fischer,

E. H., Krebs, E. G. ibid. 1971, 246, 1977.17. Khoo, J. C., Steinberg, D. 2nd int. Conf. cyclic A.M.P., 1974,

abstr. MP 30.18. Coore, H. G., Denton, R. M., Martin, B. R., Randle, P. J. Biochem.

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Polypeptides and Proteins; p. 367. New York, 1970.

22. Krahl, M. E. Fedn Proc. 1966, 25, 832.23. Hope-Gill, H. F., Kissebah, A. H., Tulloch, B. R., Vydelingum, N.,

Fraser, T. R. VII Congr. int. Diabetes Fedn: Excerpta med. abstr.1973, 54, 123.

24. Brostrom, C. O., Hunkeler, F. L., Krebs, E. G. J. biol. Chem.1971, 246, 1961.

25. Cameron, L. E., Lejohn, H. B. J. biol. Chem. 1972, 247, 4729.26. Friedman, N., Rasmussen, H. Biochim. biophys. Acta, 1970, 222, 41.27. Kissebah, A. H., Clarke, P., Vydelingum, N., Hope-Gill, H.,

Tulloch, B. R., Fraser, T. R. Eur. J. clin. Invest. (in the press).28. Ho, R., Jeanrenaud, B. Biochim. biophys. Acta, 1967, 144, 74.29. Borle, A. B. J. gen. Physiol. 1969, 53, 43.30. Clarke, P., Kissebah, A. H., Vydelingum, N., Hope-Gill, H. F.,

Tulloch, B. R., Fraser, T. R. Horm. metab. Res. (in the press).31. Allen, D., Largis, E., Miller, E., Ashmore, J. J. appl. Physiol.

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Reviews of Books

Dupuytren’s DiseaseEdited by J. T. HUESTON and R. TUBIANA. Edinburgh:Churchill Livingstone. 1974. Pp. 167. E7.

FOLLOWING the classic monograph of T. Skoog (Actachir. scand. 1948, 96, suppl. 139) and Hueston’s own

Dupuytren’s Contracture (1963), this volume is a furtherlandmark in the literature of the disease. It is the Englishedition of a book published in 1966 by the Grouped’Etude de la Main; it contains nearly thirty articles byspecialists in hand surgery. Despite the multiple authorshipthere emerges, as Tubiana shows in his concluding chapter,a wide measure of agreement on surgical care; the pendulumhaving swung away from routine radical fasciectomy, it isstressed that treatment " must be selective from all pointsof view ... There is no place for a routine operation ".Roughly half the book deals with the surgery of Dupuytren’scontracture-indications, technique, and results. The con-cept of

" Dupuytren’s diathesis " is well applied in a chap-ter describing how various prognostic factors can be usedto select the best operation in each individual case: " theresults after surgery are as much decided by the type ofpatient as by the type of surgery ". Other topics includeenzymic fasciotomy and the chemotherapy of Peyronie’sdisease. Three chapters on the anatomy of the palmodigitalfascia are outstanding, and should be studied by everysurgeon doing operations for contracture. Photomicro-graphs of serial sections through the fetal hand clearlyshow up the finer details of fascial structure, much of whichwould be destroyed by dissection. Awareness of how con-tracted bands can distort the digital nerves helps to safe-guard those nerves at operation. The illustrations are of agenerally high standard, though lavish in places and notalways related to the text. For a book of this qualitythere are far too many errors; whole lines are misplacedand references are omitted. Moreover, in a work based onpapers presented at an orthopaedic congress it is disturbingto come across an outdated method of recording jointmotion and-more serious-reference to fingers bynumber rather than by name. The book as a whole will beof interest not only to hand surgeons but to all who wishto delve more deeply into this fascinating disease.

148

The Poisoned Patient

The Role of the Laboratory. Amsterdam and New York:Associated Scientific Publishers. 1974. Pp. 335. D.fl. 55;$21.20.

IT is clear from the proceedings of this Ciba Foundationsymposium that techniques for identifying and quantifyingdrugs in biological fluids have reached new heights ofsophistication. It is equally clear that in many instancesclinicians caring for poisoned patients have not yet cometo terms with this methodology and in many cases positivelyeschew it. Among the techniques described for drugidentification and measurement are various applications ofchromatography-thin layer, gas/liquid, and liquid/liquid.An innovation is the linking to mass spectrometry of liquid/liquid chromatography, which presents quite different

problems to those of gas/liquid chromatography linked tomass spectrometry. As if these techniques were not

sufficient, luminescence, immunoassay, and radioisotopicmethods (e.g., double radioisotope dilution) are now readyfor analytical service in the care of the poisoned patient.Each of these techniques is dealt with in considerable detailwith a commendable emphasis on practical problems aswell as basic theory. An iconoclastic and timely section isdevoted to the " manufacture " of drug metabolites byapparatus used for their detection. In many ways, how-ever, the most interesting sections in this book are thediscussions between laboratory workers and clinicians.97 pages are devoted to these, and not a page too much.From these emerge several important points. Changes inplasma drug concentration, however measured, may bemisleading in judging the progress of the poisoned patient,since these may give little indication of the removal ofdrug from the tissues. Claims for the success of tech-niques such as hxmodialysis and forced diuresis in remov-ing drugs from the body are often spurious and anecdotal.Forced diuresis, especially, is a potentially lethal tech-

nique with probably a less important role in therapy thanhitherto held. The impression is of a technology severaldimensions ahead of the practical ability to use it: inter-action between these two aspects is small and must beincreased, and this volume goes a long way towards doingjust that.

Exercise Testing in Children

Applications in Health and Disease. SIMON GODFREY,M.R.C.P., Hammersmith Hospital, London. London:Saunders. 1974. Pp. 168. S5.

THIS book describes the methods available for measuringthe response to exercise in children, both in health anddisease. It reports normal values and the abnormalitiesto be expected in disease affecting the lungs and heart.The book is highly technical, but Dr Godfrey presents thematerial in a readable form with numerous clear tablesand graphs. An introductory chapter explains the valueof exercise tests and ethical implications. This is followedby two chapters which describe in detail the methods ofmeasuring the response to exercise, including change inheart-rate, ventilation, gas exchange, maximum oxygenuptake, and cardiac output. The various types of exerciseavailable are discussed. Emphasis is laid upon non-invasivetechniques for the measurement of cardiac output. Thereis a chapter outlining the response of normal children toexercise, followed by chapters on the response of childrenwith asthma, heart-disease, and other conditions. Althoughthis is a book for the specialist, it will be invaluable foranyone setting up a laboratory for respiratory-functiontesting. Much of Dr Godfrey’s description of methods ofmeasurement and the values reported in health and diseaseis derived from his own extensive personal experience, butthe literature is also widely cited.

Sports MedicineEdited by ALLAN J. RYAN, M.D., University Health ServiceMadison, Wisconsin; and FRED L. ALLMAN, JR., M.D.

Sports Medicine Clinic, Atlanta, Georgia. New York aniLondon: Academic Press. 1974. Pp. 735.$42; E20.20.

THIS is an interesting book on a topic for which there arcfew comprehensive texts. Although sports medicine halbeen recognised as a specialty in Europe for many years, iis only gradually gaining respectability in Britain. Thi:volume has been written by seventeen contributors, mostof them specialists in physical medicine and rehabilitatiorand physical education, and all from the United StatesIt starts with an historical background as far back as theancient Greeks, and passes on to the concept of physicafitness and the limits of human performance. Medica

supervision of the athlete and his sports injuries is describe,in detail. Four chapters are devoted to special physicaleducation with particular reference to the disabled. Finally,the value of exercise from the viewpoint of prevention andtreatment of disease is considered. This book will be usefulto all doctors working in sports medicine and will makfascinating reading for many others who are simply inter-ested in physical activity as a whole. In an age when theneed for exercise to counteract the effects of living in ahighly mechanised society is becoming more and moreimportant, the topics discussed need wider disseminationand could with value be introduced to medical students.

HistologyA Text and Atlas. JOHANNES A. G. RHODIN, M.D., PH.D.,New York Medical College. London and New York:Oxford University Press. 1974. Pp. 803. E9;$20.

THIS lavishly illustrated book was written for medicaland biology students and is intended to fulfil the dual roleof textbook and atlas. The right-hand pages are devotedto illustrations, with the text and legends on the left.The illustrations are almost all black-and-white photo-micrographs, of which at least two-thirds are taken at

electron microscope level. A few schematic drawings arealso used, but there are no colour plates. Medical students,whose practical work is still largely confined to the lightmicroscope, will bemoan the author’s preference for low-power electron micrographs instead of high-power lightmicrographs which would have provided them with muchmore assistance in recognising individual cell types withintissues. Nevertheless, with an up-to-date, comprehensive,concise, and readable text, a competitive price, and numer-ous illustrations, the book has much to recommend it.

Blood

Physiological Pharmacology, a Comprehensive Treatise,vol. V. Edited by WALTER S. ROOT and NATHANIEL I.BERLIN. New York and London: Academic Press. 1974.

Pp. 588.$44.50; S21.35.

THIS book is intended for haematologists and pharmaco-logists interested in the interrelationships between thesetwo disciplines. It contains 17 up-to-date reviews, mostlyby American haematologists. Most of the articles are of a

very high standard, though there is a small element ofreviewing reviews. The sections on coagulation, on stemcells, and on iron are especially good. Unfortunately, thisbook is not the comprehensive treatise it claims to be.Readers interested in the hsematological side-effects ofdrugs will soon find that this is not a very useful work ofreference. Many will consider the price too high.

New Editions

Tenth Symposium on Advanced Medicine. Edited by J. G. G.Ledingham. London: Pitman Medical. 1974. Pp. 475. E6.

Fish’s Clinical Psychopathology. Edited by Max Hamilton.Bristol: Wright. 1974. Pp. 126. E2.75.