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We ascribe the lack of complications to the small dose ofrt-PA; apart from one popliteal haematoma no bleedingepisodes were observed, no transfusions were needed, andplasma fibrinogen levels did not change.

Lysis of chronic arterial occlusions in the femoral arteryby intravenous infusion is rarely used because of themethod’s low efficiency and serious bleeding complications.Lysis by infusion of rt-PA through an arterial catheter, withgradual advancement of the catheter, has been advocatedmainly for the treatment of acute thrombosis.8 When achronic arterial occlusion is dilated and split it creates a largethrombogenic surface. However, the split thrombus also hasmore exposed surface susceptible to thrombolysis. Ourdouble balloon catheter was designed to keep local rt-PAand heparin concentrations high and to avoid generalfibrinogenolysis. Rt-PA is a highly effective thrombolyticagent. It was chosen because it binds to fibrin and therebyallows thrombolysis to continue even after removal of thecatheter.9We also had two other types of catheter constructed but

they were not used in the patients reported here. To do PTAand locally enclosed lysis with the same instrument, a fourlumen, 7-French double balloon was made, in which eachballoon was inflated by separate channels. Angioplasty canthen be done through the balloon at the tip of the catheter. Afive lumen 7-French catheter with two sideports close to andbetween the balloons was also constructed. By flushingrt-PA through the sideports mixing might be improved.

Fibrin and fibrinogen degradation products were slightlyincreased 30 minutes after the catheters were removed

although plasma fibrinogen values were normal. Possiblythe degradative processes occurred within the enclosedsegment of the femoral artery. However, how much of thedegradation is produced by the PTA procedure per se isunknown. In a sample from 1 patient, who was treated for afemoral occlusion by PTA without rt-PA, the values forfibrinogen and fibrin degradation products (0-2 mg/1 and 05mg/1, respectively) were closely similar to those of thepatients who had had rt-PA. Little is known about thesedegradation products after simple intravascularinterventions. In the present study we saw no indication ofsystemic derangement of the coagulation system. Thesefindings suggest that the procedure is safe. We need now toestablish by randomised trials whether PTA and topicallyenclosed rt-PA and heparin is an improvement on PTAalone and whether intravenous heparin for 24 hours afterPTA is as effective as the combined therapy.

We thank Boehringer Ingelheim for the rt-PA (’Actilyse’) and Dr S. W.Coppack for reading the typescript.

Correspondence should be addressed to K. H. T.

REFERENCES

1. Schneider E, Grüntzig A, Bollinger A. Die percutane transluminale Angioplastie(PTA) der beinarterien im Stadium III & IV der periferen arteriellenVerschlusskrankheit. Vasa 1982; 11: 336-42.

2. Gallino A, Mahler F, Probst P, Nachbur B. Percutaneous transluminal angioplasty ofthe arteries of the lower limbs: a five year follow up. Circulation 1984, 70: 619-23.

3. Topol EJ. The thrombolysis and angioplasty in acute myocardial infarction (TAMI)trial. In: Topol EJ, ed. Acute coronary intervention. New York: Alan R. Liss, 1988:153-74.

4. Chantarang V, Tnkodt A, Mannuici PN. Instrumentation laboratory, SpA, code80810-01: evaluation of a fully autorated centrifugal analyzer for performance ofhaemostasis tests. Clin Chem 1987; 33: 1880-90.

5. Koppert PW, Hoegee de Nobel E, Niewenhuisen W. A monoclonal antibody-basedenzyme immunoassay for fibrin degradation products in plasma. Thromb Haemost1988; 59: 310-15

6. Goldhaber SZ, Vaughan DE, Markis JE, et al Acute pulmonary embolism treatedwith tissue plasminogen activator Lancet 1986; ii 886-89.

7. Tønnesen KH, Sager P, Karle E, Hennksen L, Jørgensen B Percutaneoustransluminal angioplasty of the superficial femoral artery by retrogradecatheterization via the popliteal artery. Cardiovasc Intervent Radiol 1988; 11:127-31.

8. Graor RA, Risius B, Denny KM, et al. Local thrombolysis in the treatment ofthrombosed arteries, bypass grafts, and artenovenous fistulas. J Vasc Surg 1985; 2:406-14

9 Collen D. Biological properties of plasminogen activators. In: Sobel BE, Collen D,Grossbard EB, eds. Tissue plasminogen activators in thrombolytic therapy. Basel,New York: Marcel Dekker, 1987. 3-25.

Reviews of Books

Cardiac Arrhythmias: The Role of TriggeredActivity and Other Mechanisms

Paul F. Cranefield and Ronald S. Aronson. New York: Futura.1988. Pp 706.$125. ISBN 0-879933275.

MORE than four decades ago Hoffman and Cranefieldwere among the first to employ microelectrodes to recordpotentials from single cells in multicellular preparations ofcardiac tissues. They named the "phases" 0-4 of the cardiacaction potential, and introduced nomenclature-eg, "earlyafter-depolarisation", "membrane responsiveness"-thatbecame the jargon of electrophysiologists trained inAmerican centres. The terms were purely descriptive, notspecifying the underlying ionic currents responsible for thephenomena. The European emphasis, following the work ofHodgkin, Huxley, and others, was on analysis of the control,by transmembrane voltage, metabolic activity, or drugs, ofthe selective channels through which ionic currents flowedinto and out of cardiac cells.

Cranefield and Aronson have now endeavoured to

synthesise the two approaches, especially in relation tocurrents that may cause "after-depolarisations" initiating"triggered activity", the major topic of their book. Thesinoatrial node contains specialised "pale" cells (p-cells)with low resting potentials which spontaneously depolarise.They are poorly coupled to each other, but closely coupledto surrounding cells which they activate, causing a circularwave of action potentials to spread out from the node.Similar cells occur in the A-V node and proximal ventricularconducting tissue, and are responsible for "normal

automaticity" after A-V block. The peripheral Purkinjeconduction cells do not pace-make in situ, but can do so ifexcised and exposed to low extracellular potassium.Surprisingly the authors consider such pacemaking as

"normal automaticity" also. This is contrasted with thebehaviour of other excised tissues, such as coronary sinuscells, which are quiescent but, if stimulated, may continueto produce action potentials spontaneously on cessation ofstimulation. This is "triggered activity", of interest as apossible cause of cardiac arrhythmia.The triggered action potentials are initiated by "delayed

after-depolarisations" which, if subthreshold for excitationof full action potentials, may exhibit oscillatory activity. Issuch triggered activity relevant to arrhythmogenesis in man?The heart must beat continuously for survival, so that,except in the rare event of resuscitation from cardiac arrest, a

1109

trigger is always present. As the authors themselves

conclude, "Few, if any, clinically significant arrhythmiashave been proven to result from triggered activity".

Nevertheless, a large proportion of this volume isconcerned with the circumstances in which delayed after-polarisations may be induced in isolated tissues, and with theionic current that has been postulated to be responsible,often referred to as "transient inward current" (Ti), butwhich, as the authors are careful to point out, is not

necessarily the same current in different situations.Transient inward current was induced by various means invarious preparations. The concentrations of cardiacglycosides required to induce Ti were several times thelethal human concentration. If such extreme procedures arenecessary to induce Ti, it seems doubtful whether Ti couldbe an "arrhythmogenic current" in man, whose survivalrequires control of the cellular environment within narrowlimits. A great deal of effort has, however, gone into attemptsto elucidate the nature of Ti, and chapter XXI discusses indetail the numerous explanations that have been offered-eg, Na/Ca electrogenic exchange, and Ca-activated cationicchannels.

"

In his foreword, Hoffman writes: "This a truly greatbook. It demonstrates impeccable scholarship and anoutstanding depth and breadth of understanding. It is inpart encyclopedic ...". Indeed, the authors, not wishing toomit any evidence that is germane, have reviewed in detailmany papers of no obvious relevance to their main theme,and this makes some chapters hard going. The overall effectis somewhat depressing in that one comes to appreciate howlittle that is useful or secure has emerged from the millions ofman-hours devoted to research. The volume seems to be acompendium of speculations. This is no fault of the authors;one cannot blame the messengers for bad news.

In conclusion, this volume can offer the clinical

cardiologist acquaintance with recent research in cellularelectrophysiology but is unlikely to improve insight into theorigin of human cardiac arrhythmias or facilitate therapy.The last sentence is: "Afterpotentials, which can cause somany arrhythmias in vitro must surely cause some, andperhaps many, of the arrhythmias that afflict the heartitself." On the evidence presented, not proven.153 Woodstock Road,Oxford OX2 7NA E. M. VAUGHAN WILLIAMS

Reproductive Endocrine TherapeuticsEdited by R. L. Barbieri and 1. Schiff. New York: A. R. Liss.1988. Pp 430.$59.50. ISBN 0-845142607.

IN most reviews of reproductive endocrinology-a newone seems to arrive every week-the emphasis is on thepathology of the disorder. Barbieri and Schiff, however, tryto cover as completely as possible the therapeutic methodsavailable for the treatment of disorders associated with

reproductive endocrinopathies. Their approach is hormoneand drug based rather than disease based; they assume thatreaders will already know much about the individualdisorders.

Multiauthorship has given rise to a lot of repetition-forexample, several contributors describe the structure andphysiology of gonadotropin releasing hormone. Earlypregnancy wastage, endocrinology of malignancy, the

endorphins, and catechol oestrogens receive little attention,

but most other important endocrine topics are covered.British publications suffer neglect in some contributions-for example, there is nothing on suppression of ovulation byoestrogen patches, the efficacy of oestradiol implants inpremenstrual syndrome, or the management of cyclicalmastalgia. Many of the chapters describe in numerical detailthe economics of various treatment methods; I am sure thatthis will become a necessity in British publications of thefuture.

Though the book presents little that is new, it has themerit of providing a landscape view of the endocrinetreatment of many of the important reproductive disordersincluding endometriosis, fibroids, hirsutism, premenstrualsyndrome, anovulation, infertility, menopause and

osteoporosis, precocious puberty, and gonadal dysgenesis.Virtually every relevant drug and hormone therapy isdiscussed in detail. I strongly recommend this text as anexcellent and readable knowledge base for gynaecologicaland reproductive endocrinologists.Academic Department of Obstetrics

and Gynaecology,Royal Free Hospital School of Medicine,London NW3 2QG P. M. S. O’BRIEN

Multiple Sclerosis-A Conceptual Reappraisal withHeuristic Implications

E. J. Field. Springfield, Illinois: Charles C. Thomas. 1989.Pp 255.$49.75. ISBN 0-398055262.

E. J. Field has always been a controversial figure and hasacted as an agent provocateur for some 30 years. This book istrue to form. It is a very individual account of multiplesclerosis and is peppered with quotations from Nietzsche,Claude Bernard, Charcot, and other prominent figures pastand present. A foreword by Hugh Sinclair points out thesignificance of Professor Field’s work on the effects ofessential fatty acids on the electrophoretic mobility oferythrocytes.The book begins with a conceptual reappraisal of multiple

sclerosis and this is followed by an historical introductionwhich is a mixture of social comment, selected quotations,and a commentary on the development of ideas regardingmultiple sclerosis. In the section on the pathology ofmultiple sclerosis, Field concentrates on the perivascularlocation of the plaques and the nature of the early lesions.This chapter is scattered with anecdotes from which welearn that neither the late R. M. Norman nor the

well-respected Ludo van Bogaert possessed an oil-immersion lens on his microscope.A large section of the book is devoted to laboratory tests

for the multiple sclerosis diathesis, and is mainly devoted tovariations of the erythrocyte unsaturated fatty acid testdevised by Field and his co-workers in the 1970s. The themethat plasma seems to be all-important in the underlying redcell behaviour in the tests is also developed in this part of thebook. There is, however, little mention of other forms ofinvestigation of multiple sclerosis.The concept of multiple sclerosis as an abiotrophy is

developed in the middle section of the book and Field thenexpands into the possible familial nature of the disease. Aftera chapter on the hyperactive child, the role of essential fattyacids in multiple sclerosis is discussed, and the question isasked "Is there a family of membrane diseases?". The lastsection on the management of multiple sclerosis is followed

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by a very personal view, and proposals are put forward forfuture efforts directed towards elimination of the disease.The book is well written, although the interposition of

French and German phrases within the text detracts fromthe flow. As Field states, the text is not a comprehensiveaccount of multiple sclerosis, and he has selected from thework of various authors to substantiate his own views.

Despite the lucid nature of the text, one unfortunate featureruns throughout the whole book: the whole constructiontends to go against the scientific method. Although hequotes Popper with approval, Field has not followed

Popper’s method. The observations are there and thehypotheses are there, but he has made the mistake of quotingselectively from other people’s work to substantiate hishypotheses. He has concentrated on proving his hypothesesrather than disproving them.

If you are searching for an informative, traditionalaccount of multiple sclerosis, this is not the book for you. Ifyou are looking for a stimulating text and a rather

idiosyncratic, iconoclastic account of the pathology,investigation, and management of multiple sclerosis, then itwill suit you very well.

Department of Neuropathology,University of Southampton R. 0. WELLER

Clinical GastroenterologyEdited by L. A. Turnberg. Oxford: Blackwell ScientificPublications. 1989. Pp 537. 39.50. ISBN 0-632014733.

Professor Turnberg and his colleagues have managed tocover, in 24 chapters, the main dilemmas and disordersencountered in gastroenterological practice with a well-crafted blend of consensus wisdom and individual expertopinion. Some chapters consider symptoms or particularclinical problems (eg, upper gastrointestinal haemorrhage,constipation) whereas others are disease or organ based(peptic ulcer, gallbladder disease, chronic liver disease) butconsistency of style renders the oscillation of approachbarely noticeable. All fifteen authors are past or presentmembers of the departments of medicine and surgery atHope Hospital, Salford, and it is presumably this commonbackground, plus good editing, which has enabled thecoherence to be achieved.The aetiology, pathogenesis, and pathology of

gastrointestinal disease is given very limited attention andthis deliberate restriction probably goes too far. One doesnot have to belong to the "molecular biology explains all"brigade to believe that good clinical judgment requires a fairknowledge of the relevant basic science. Admittedly, it isvery difficult to strike the right balance in any text that aimsprimarily to be of practical value.

If a book is to be judged by its ability to inform andstimulate the reader, this one scores well. The uncertaintiesand choices of patient management do require this sort ofconsideration; and, if a few topics have been omitted, so be it,for this does not purport to be an ordinary textbook. It willbe interesting to see whether the next edition, a few yearshence, relates the costs of investigations and therapies to thedecisions on patient management. This is something we allsupport, isn’t it?

Department of Medicine,Royal Infirmary,Edinburgh EH3 9YW R. C. HEADING

A Colour Atlas of Multiple Sclerosis and OtherMyelin Disorders

Colin Adams. London: Wolfe Medical Publications. 1989.

Pp 231. /;55. ISBN 0-72340528.

NEUROPATHOLOGY must be one of the few specialties inwhich colour reproduction is essential to illustrate the effectsof diseases upon tissues. Unfortunately most publicationsare monochrome, and even beautiful myelin pictures lookaustere. Professor Adams has produced a magnificentcolour atlas. It consists of short chapters separated byclusters of superb illustrations, largely in colour, andtotalling nearly 500.The first half deals with myelin structure and the effect of

diseases other than multiple sclerosis upon it. Thediscussion is wide-ranging and contains numerous humanand animal diseases, including some that deviate a little frombeing purely demyelinating disorders. The second half dealswith multiple sclerosis and its variants. Although this isprimarily a pathological text Adams demonstrates his wideknowledge of the disease with chapters on aetiology,epidemiology, and immunology. The chapter on the

histology of the multiple sclerosis lesion is outstanding, witha large number of illustrations. This chapter and the one onvascular involvement graphically dispel the notion thatneuropathology is a dead subject-the former because of theuse of many monoclonal stains to demonstrate mechanismsof demyelination, the latter because of the increasingevidence that vascular involvement is crucial to

development of the disease.I strongly recommend this publication to scientists and

clinicians alike.

Maida Vale Hospitals,London W9 1TL PETER RUDGE

Septicaemia and Endocarditis: Clinical andMicrobiological Aspects

Edited by D. C. Shanson. Oxford: Oxford MedicalPublications. 1989. Pp. 177. /;25. ISBN 0-192615076.

David Shanson assembled a very strong team for thisshort review volume, avoiding parochialism by invitingJ. McGowan from Atlanta and L. Young from SanFrancisco to join himself and T. Rogers from London, R. G.Finch from Nottingham, and W. A. Littler from

Birmingham. Thus the balance also extends to disciplines(medicine, cardiology, infectious diseases, and medicalmicrobiology). The result is an up-to-date review of thecauses, prevalence, diagnosis, and management of

septicaemia with a separate chapter on endocarditis. Morethan 20% of the book is devoted to listing the 600 paperscited, and the reference style does not make for easy reading.Nonetheless, the reader is provided with a very

comprehensive and practical account of the problemsinvolved, and is given clear guidelines on how to approachthem. There is some overlap between sections-for

example, two contributors discuss the important paper ofPizzo et al comparing ceftazidime monotherapy withantibiotic combinations-but this is welcome when itreinforces key points. In such an advancing topic the lastword is never possible, but this review is as near to it aspracticable.

Papworth Hospital,Cambridge CB3 8RE S. W. B. NEWSOM