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(patients 4 and 7) is taken as a response, the significanceincreases to p<0 00 1.

Several patients deviated from the protocol in that theystopped taking stilboestrol as soon as the priapism resolved,rather than for the full 14-day period as instructed.

Maintenance TherapyOf the 9 patients apparently responding to stilboestrol,

attacks resumed within 2-8 weeks of the cessation of therapyin 5 patients (patients 4 and 6-9). In these patients, attemptswere made to titrate the minimum dose of stilboestrol

necessary to allow normal erections but to prevent a

recurrence of stuttering priapism. The dose varied betweenindividuals and within individuals at different times. Patient4 did not respond to stilboestrol 2’ 5 mg weekly but was freeof symptoms on 2 - 5 mg every 3 days. Patient 6 found initiallythat 5 mg tablets gave relief for 3 nights and 2 - 5 mg relieffor 2nights but later noted that relief from 2 - 5 mg lasted one weekand currently 3 weeks before mild priapism recurred. Patient7 had control of symptoms on 2 - 5 mg on alternate days buthad a major attack 2 months later. Patient 8 responded wellinitially but recurrence of attacks was associated withdiminished response and latterly 5 mg daily afforded onlyintermittent relief. Patient 9 remains well controlled on 2’ 5

weekly over the past 14 months.The relation of stuttering attacks of priapism and painful

crises during this period was also of interest. 1 patient (9)remarked that attacks of priapism always ceased transientlyafter a painful crisis and occasionally before. Over a 20-monthobservation period which included 3 severe attacks of bonepain requiring hospital admission, priapism ceased for 4-6days before bone pain and for 6-8 days afterwards. Patient 8had.5 days of relief from priapism after a painful crisis butnone prodromally.

DISCL’SSlOX

The mechanism of priapism in sickle-cell disease is not wellunderstood but attacks are presumed to result from impaireddrainage of the corpora cavernosa due to poor deformabilityof erythrocytes. Many measures have been proposed butnone have given consistent relief and few, if any, have beensubjected to controlled trials. Preliminary experience in theJamaican sickle-cell clinics suggesting that stilboestrol mayterminate attacks of stuttering priapism has now beenconfirmed in this trial.The erratic and unpredictable natural history of attacks of

stuttering priapism complicates the assessment of therapy.Typically starting soon after puberty, attacks may continuefor weeks, months, or years during which priapism lasting1-6 h occurs nocturnally as often as every night. Mild attacksconsist of infrequent priapism of short duration for a fewweeks; serious attacks consist of nightly priapism for months.Attacks may start or stop at any time but severe attacks maybuild into a crescendo that terminates with a major attack ofpriapism (sustained erection for more than 24 h) commonlylasting 3-5 days, and extreme pain. Following this thevascular system of the corpora cavernosa is permanentlydamaged and the recurrence of erections, either with

priapism or naturally, is rare.How stilboestrol exerts its effect is unclear; it may be by a

"neutralising" effect on male hormones or a direct effect onerythrocyte characteristics. Side-effects include mild

gastrointestinal symptoms, gynaecomastia, and loss ofnormal erections, but with the low doses used in maintenance

therapy gynaecomastia was seen in only 1 out of 5 patientsand it was generally possible to find a dose which allowednormal erections but prevented priapism. The effects oflong-term low-dose stilboestrol and the natural history ofstilboestrol-suppressed stuttering priapism remain to bedetermined.The relation between stuttering priapism and the painful

crisis was of great interest because priapism ceased forvariable periods following painful crises and occasionally forsome days preceding. There is evidence that the proportion ofdense red cells falls during the painful crisis3 and this removalof a population of cells most likely to cause vessel obstructionmay account for the transient relief from priapism. Thishypothesis gives an interesting and testable insight into thepathophysiology of attacks of priapism in sickle-cell disease.Much remains to be learnt about how stilboestrol seems to

prevent this distressing complication. Attacks may be abortedby stilboestrol 5 mg daily for 3-4 days and may be preventedby much lower doses.

Correspondence should be addressed to G. R. S.

REFERENCES

1. Emond AM, Holman R, Haves RJ, Sergeant GR. Priapism and impotence mhomozygous sickle cell disease Arch Intern Med 1980; 140: 1434-37.

2. Serjeant GR The clinical features of sickle cell disease. Amsterdam: North HollandPublishing Company, 1974

3 Fabry ME Benjamin L, Lawrence C, Nagel RL. An objective sign in painful crisis insickle cell anemia: the concomitant reduction of high density red cells. Blood 1984,64: 559-63.

Books

Human ExperimentationA Guided Step into the Unknown. William A. Silverman, formerlyColumbia University, New York. Oxford: Oxford University Press. 1985.Pp 204. 20.

Dr Silverman was formerly Professor of Pediatrics at ColumbiaUniversity, and is an ardent, even passionate, advocate of therandomised clinical trial. He quotes his colleague, Mervyn Susser,who likened the importance of the technique of the clinical trial "tothe abrupt advance following the invention of the microscope".Such hyperbole will perhaps be greeted with some scepticism.bycynics who recollect that the introduction into medical practice ofinsulin, liver treatment of pernicious anaemia, penicillin, andoperative closure of patent ductus arteriosus required no suchanalysis. This volume does not encompass, as one might expectfrom its title, the general field of human clinical investigation, butspecifically limits its scope to a consideration of the randomisedcontrolled clinical trial. The author draws heavily on his experienceas a practising paediatrician and especially on his own importantcontribution to the discovery that oxygen therapy may damage theeyes of newborn infants. The work starts with a historial perspectiveand goes on to describe the techniques necessary for carrying outeffective clinical trials. There are chapters on framing the question,the selection of test subjects and controls, how to intervene, what toobserve, what to avoid, and, most difficult of all, how to know whento stop. There are also useful discussions of concepts of statisticalproof and how to take practical action in the face of uncertainty. Aconcluding chapter considers the ethics of human experimentation.There is in addition an appendix which sets out the story ofretrolental fibroplasia which the author has already described ingreater detail in an earlier book. The book puts forward the views ofa thoughtful academic on the significance of clinical trials in themodern era effectively and well. There are important warnings tothe gullible on the fallibility of apparent medical advances.Although it appears that the work has been written with the generalreader in mind, there is much in these pages that will not be readilyappreciated by the non-expert. For others, however, the book is an

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engaging and well written account of an important part of modernmedical research.As is now fashionable in such undertakings, suitable obeisance is

done to gurus such as Macfarlane Burnet and Karl Popper, as wellas to Peter Medawar. In addition, as perhaps befits the work of azealot, the book has been liberally festooned with quotations,framed in black like religious texts in the home of a Victorianevangelist. There are selections from James Lind, Fisher’s

arguments on agricultural field trials, Wesley’s journals, T. H.Huxley on chess, extracts from the Books of Kings, Ezekiel, andDaniel, and a hackneyed passage from St Paul’s first epistle to theCorinthians. There are some, for example Archibald Macleish’scomment that "we have learned the answers, all the answers; it is the

question that we do not know" which will perplex rather thanilluminate. Many of these epigrammatic contributions might wellgrace the pages of a commonplace book. Whether they make a usefulcontribution to a volume which is limited to the importance ofclinical trials is more questionable. The price of 20 for less than200 pages of text makes this expensive reading.Clinical Research Centre,Harrow,Middlesex CHRISTOPHER BOOTH

Virus Disease of the EyeDavid Easty, University of Bristol. London: Lloyd-Luke (EdwardArnold). 1985. Pp 350. 30.

THIS monumental work gives an authoritative, clear account ofthe types of virus that affect the eye, their structure, and thelaboratory techniques used in their detection. The clinicalconditions produced by the different viruses are well described, andthere is a comprehensive discussion of the possible mechanisms bywhich the different clinical signs have been caused, and of themanagement of each clinical entity. The discussion of the relevantliterature is interesting, unbiased, and highly informative.My main criticism is that with such a detailed text, it is sometimes

difficult to isolate the relevant facts and obtain a clear picture of themanagement of a particular disease. This difficulty could have beenovercome by the use of tables of clinical signs and their

management, and a summary at the end of each chapter.There are one or two omissions or small criticisms. For instance,

m herpes simplex infection, the text does not tell how to distinguishbetween active herpes simplex corneal ulceration and thebreakdown of an inert ulcer causing a recurrent erosion. Themanagement of these two conditions is entirely different. These areminor points, however, and do not detract from the overallexcellence of the book. It is well written, highly informative, andshould be on the shelves of all eye hospitals, available to anybodywith an interest in ocular infection. It is highly recommended.

Southampton Eye Hospital,Southampton JAMES I. MCGILL

The Scientific Principles of PsychopathologyEdited by P. McGuffin, Institute of Psychiatry, London, M. F. Shanks,University of Glasgow, and R. J. Hodgson, Whitchurch Hospital,Whitchurch, Cardiff. Orlando, Florida and London: Grune and Stratton.1984. Pp 780.$60; 35 (UK only).

IN this multi-author book on the sciences basic to psychiatry, theeditors’ definition of science is broad-from the relatively "hard"subject matter of biochemistry and anatomy, to the "softer" theoryof sociology and psychoanalysis. Thus it reflects accurately thenature of psychiatry. The book is aimed primarily at meeting theexamination needs of psychiatrists and psychologists in training,but it will also serve to inform the trained clinician in his practice.There are six sections. Part one covers the neurosciences, with

chapters on the functional morphology of the central nervoussystem, neurophysiological principles and clinical application ofelectroencephalography, neurochemistry, neuropharmacology andpharmacokinetics, neurotransmission, and endocrine changes inmental illness. Part two consists of three highly informativechapters by Dr McGuffin on the genetics of normal and abnormalbehaviour. Principles and methods in psychiatric genetics, genetic

influences on intelligence and mental handicap, personality,neurosis, and psychosis are all covered. In part three, three ratherdisparate chapters are grouped uneasily under the title of the lifecycle. The topics covered are child development, acquisition oflanguage, and psychological aspects of ageing.Nine chapters on psychology and sociology in relation to

psychiatry comprise part four. Social learning theory, behaviouralpsychotherapy, personality, and neuropsychology are covered.There is an intriguing section on the "lunatic left" which turns outnot to be a political discussion but an evaluation of the evidencelinking schizophrenia to left hemisphere pathology. There areuseful accounts of the nature and measurement of intelligence, thepathology of memory, and techniques of psychological assessment.Selected concepts in sociology and social anthropology are

reviewed-for example, the meaning of mental illness, deviancytheory, cultural influences on illness, life events, and the sociologyof treatment. The final chapter in this section covers small-

group phenomena. Part five consists of three chapters on

psychopathology. Experimental and descriptive psychopathologyare discussed, and there is a helpful and readable account of basicconcepts in psychoanalytic theory. Part six deals with the theoryand practice of psychiatric research, with chapters on statistics,experimental design, and the elements of epidemiology. Theconcluding chapter is an illuminating discussion on the topic ofphilosophy and psychiatry in which concepts such as causality andmeaning are considered.Throughout this book the references are selectively chosen and

the quality of production is high. It is readable, and for a few yearswill probably become a standard text for aspirants to the

MRCPsych examination-both in its present form and in themodified form which will be introduced in the autumn of 1987.

Department of Psychiatry,Royal Dundee Liff Hospital,Dundee ANDREW H. REID

Tumor Markers

Clinical and Laboratory Studies. Jams V. Klavins, Cornell UmversityMedical College, New York. New York: Alan R. Liss. 1985. Pp 198. 37.

THE idea of following the serum level of a substance in a patientwith cancer so that the course of the disease can be deduced and

appropriate decisions about treatment made, is very attractive. Thisbook is claimed in the publisher’s information to be a completereference guide for further study of tumour markers. The prefacestates that it is intended for clinicians, investigators, and students.The appeal to students must be extremely limited; the one-pageintroduction defines in very basic terms what tumours and tumourmarkers are but there is no description of the role of markers inclinical practice, nor are the histochemical uses discussed. Studentswill also be misled by the inclusion of alpha-1-acid-glycoprotein andsialic acid in a section introduced as a list of products of tumourcells.The clinician seeking guidance on the use of tumour markers in

practice will also be disappointed. Carcinoembryonic antigen iscovered in some detail, although to gain a complete picture it isnecessary to consult several short sections throughout the book.The well established use of human chorionic gonadotropin andalpha-fetoprotein in germ-cell tumours is mentioned very briefly,while paraproteins in multiple myeloma are dismissed in two lines.The people who will find this book most useful are those

investigating the use of markers in either the clinic or the laboratory.For them it functions as an annotated bibliography to assist ininitiating a literature search. For most markers this book can do littlemore than that because only a short paragraph, with one or tworeferences, is given to each. Even for relatively well knownsubstances the information reported is not very up to date. Thus theCal antibody is mentioned with references to the initial optimisticreports in 1982 which suggested that it was a highly specific markerfor malignant disease; the papers that followed shortly afterwards,and showed that this substance is more widely distributed, are notmentioned, even though they appeared two years before the bookwas published.

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It is amazing to come across a book published in 1985 whichrecognises only two types of HTLV. The term "gene product"occurs throughout the text; this is useful in discussing such things asthe function of oncogenes but it is an unnecessary synonym for

protein and a not specially accurate one for glycoprotein. With onepage of references for every three of text, this volume has some

potential as an introduction to the literature, but it is difficult to seewho will consider the cost justifiable.

Department of Medical Oncology,Channg Cross Hospital, London S. M. CRAWFORD

NeurotoxicologyDrug and Chemical Toxicology, vol3. Edited by Kenneth Blum, Universityof Texas Health Science Center, San Antonio, Texas, and Luigi Manzo,University of Pavia Medical School, Pavia, Italy. New York: MarcelDekker. 1985. Pp 676.$99.75 (USA and Canada).$119.50 (all othercountries).

THE proliferation of texts on neurotoxicology is an indicationboth of the number of experimental and clinical studies carried outin recent years and of the increasing appreciation of the importanceof this topic in disease prevention. Experimental toxicology has thetwo-fold purpose of analysing lesions produced by specific toxicsubstances and of using these substances as tools to dissect normalfunction of the nervous system. Clinical studies following exposureto known toxic substances are directed to studying the acute effectson humans, but increasingly clinical interest is in public healthproblems related to levels of exposure, minimal toxic effects, andpossible adverse effects on higher cerebral functions such as moodand memory.Dr Blum and Dr Manzo have in no way edited a comprehensive

treatise on neurological effects of toxic chemicals. Rather, their aimwas to provide new information, ideas, and descriptions of moderntechniques "to help answer current questions". The topics are thusselected. The first section covers pathophysiology and targetsystems generally, whereas the second and third describe particularsubstances, drugs, and environmental chemicals. The last sectiondiscusses methodology.In the first section J. B. Cavanagh gives, as usual, a stimulating

account of current concepts of the basic mechanisms underlyingtoxic peripheral neuropathies. Unfortunately, one of the legends(fig 1, chapter 1) describes incorrectly the lesions on the single fibresillustrated (from one of my own publications!). Other chaptersencompass mainly the pharmacological aspects of autonomic,neuroendocrine, and sleep systems and of drugs of addiction. Agood chapter on genetic aspects of neurotoxicity gives a valuableand up-to-date summary of a topic which will probably becomeincreasingly important in understanding the epidemiology of toxiceffects. Chapters on specific neurotoxicants are also up to date.This volume, without being totally comprehensive, gives a useful

glimpse of the current foci of active investigation in

neurotoxicology to those outside the field who might be interested.For the moment it will also provide a useful summary and source ofreferences on a number of topics to a variety of workers.

Unfortunately, as with so many books of this type, it is expensiveconsidering that it is likely to be soon out of date.

The Reta Lila Weston Institute of

Neurological Studies,The Middlesex Hospital Medical School,London PAMELA M. LE QUESNE

Interface Between Neurology and PsychiatryEdited byM. R. Tnmble, The National Hospitals, London. Basle: Karger.1985. Pp 190. Sw Furl 14; DM137;$48.50.

.

ALTHOUGH neurology and psychiatry are often combined as onediscipline they are strange bedfellows. One sets high standards of

clinical diagnosis and investigation, a wide knowledge of medicine,and intellectual precision. The other often appears scientificallyvague, divorced from other medical disciplines, and preoccupiedwith hypothetical untestable concepts. Nevertheless, in a series onadvances in psychosomatic medicine it is essential to look at theinteraction between neurology and psychiatry and give it some

coherence. Dr Trimble, with his seven other contributors, has done

well to make sense of the association and to show that the disciplinesare not so far apart as some might think. Appropriately the bookstarts with another elegant account by J. Gray of his septohippo-campal theory of emotion that integrates neuropharmacology,neurochemistry, and neuroanatomy. This is followed by a

thoughtful chapter from 1. Grant on the relation between lifeevents and morbidity from neurological disease. Then there areaccounts of important neurological conditions such as epilepsy,cerebrovascular disease, multiple sclerosis, and motor disorders byacknowledged experts. A. C. P. Sims links together injury, neurosis,and accident proneness in an interesting way that I have not seendone before. In the final chapter, J. Cobb applies valiantly theprinciples of behavioural psychotherapy to neurological disordersin a carefully researched review.

I think it would be helpful for neurologists and psychiatrists toread this book; but regrettably the price is rather high. Neurologyand psychiatry are separated by only a small window butunfortunately it is constructed of frosted glass and it is difficult tosee what is happening on the other side. The main problem is thatneurologists seldom read psychiatric texts and psychiatrists are

seldom interested in neurology. It would also help greatly if conjointenterprises of this nature were shown to be of value to patients withneurological and psychiatric disorders. Apart from Cobb’s chapterand that by J. W. Paulley on multiple sclerosis (which is full oftherapeutic zeal) there is little to excite the therapist. But soundfoundations are being laid and they should yield rewards beforelong.

Mapperley Hospital,Nottingham PETER TYRER

Human Prenatal DiagnosisClmical and Biochemical Analysis, vol 18. Edited by Karen Filkins andJoseph F. Russo, University of Medicine and Dentistry of New Jersey,Newark, New Jersey. New York: Marcel Dekker. 1985. Pp 418.$75(USAand Canada).$90 (all other countries).

1 HE preface states that this volume is intended as a guide tocurrent methods of prenatal diagnosis (PND) for doctors and otherprofessionals providing care for pregnant women. The editors andall but four of the twenty-nine contributors are from NorthAmerica.The current range of prenatal diagnostic techniques and

conditions amenable to diagnosis are covered, but it is sometimesdifficult to decide whether this is a book on genetic disorders andtheir basic defects, on counselling, or a technical guide to PND.Certainly there is no uniformity of approach between the chapters,whose contents vary from extremely sketchy coverage of PND ofneural tube defects to the addendum on DNA analysis which, apartfrom being partly repetitive of the chapter on haematologicaldisorders, provides technical details of cloning and preparation ofDNA probes far in excess of the needs of the readers for whom thebook was intended.The chapter on amniocentesis for cytogenetic disorders is clear

and concise and covers safety (and risks), indications, and problemswith interpretation; it should have been a model for the other

chapters. Of interest and providing possible pointers for the futureare the chapters on embryoscopy and fetal therapy. Whilst manyreaders will be subject to different jurisdiction, the chapter on legalimplications of PND preaches good practice about the need for thepractitioner to both be informed and to inform the patientadequately.

In a volume on PND it is regrettable that post-terminationexamination of fetuses receives only fleeting reference. Our

patients, who have made the difficult decision to terminate what isusually a wanted pregnancy, should expect quality control for testscarried out (details should have been given in all chapters) andaccurate information on which to base decisions about future

pregnancies.Whilst there are interesting and novel parts of this volume, it is

poorly edited and I would hesitate to recommend this in preferenceto other texts on prenatal diagnosis.

Department of Medical Genetics,St Mary’s Hospital, Manchester DIAN DoNNA]