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The GnRH analogue used in this study is similar to anumber of other analogues which differ from native GnRHby the substitution of a D-aminoacid in the sixth position.These compounds are several-fold more potent in releasingFSH and LH than native GnRH after single doses, but long-term treatment results in severe suppression of gonadotropinlevels.3 The effects of chronic therapy on both gonadotropinsand spermatogenesis are dose-related. Smaller doses causesuppression of serum-gonadotropins with no effect on sper-matogenesis, whereas larger doses depress both. 10,1 IHow D-Ieu6 GnRH protects spermatogenesis is unclear.

The number of GnRH receptors in the pituitary changes 3-4fold during the normal oestrous cycle in rats.l2 Thus, it ispossible that long-term administration of GnRH or ananalogue leads to diminished pituitary GnRH responsivenessby down-regulation of GnRH receptors in hormone excess,as has been observed with other peptide hormones. On theother hand, testicular receptors for GnRH have beendemonstrated in interstitial tissue, and GnRH has beenshown to produce a significant decrease in LH receptors oninterstitial cells, with a dramatic fall in testosterone produc-tion.13,14 In the first case, the rise in FSH/LH expected aftertesticular injury would be prevented by pituitary unrespon-siveness to intrinsic GnRH release. In the second case, a risein LH would not have a normal stimulatory effect ontesticular steroidogenesis whichs necessary to maintain nor-mal spermatogenesis.

Paradoxically, testosterone administration can also sup-press spermatogenesis, probably through suppression ofFSH and LH. Maximum suppression of gonadotropins hasbeen achieved by combining testosterone and GnRH-

analogue therapy.4 Ultimately, the most effective regimen forprotection of germinal epithelium may be a combination ofGnRH analogue and testosterone. The concomitantadministration of testosterone would also be advantageousin preventing the signs and symptoms of androgeninsufficiency.We have no information as to whether treatment with

D-Ieu6 GnRH affects the sensitivity of other tissues to

cyclophosphamide. It is possible that the increased mortalityin group C could result from increased myelosuppression inthe absence of androgens. Further studies will be required toanswer this as well as the question of potential interferencewith the antitumour effect of the chemotherapy.This study provides the first evidence that interruption of

the pituitary-gonadal axis may protect spermatogenesis fromthe effects of cytotoxic chemotherapy. Longer-term breedingstudies are needed to determine whether the residual germcells seen in the animals protected by D-Ieu6 GnRH can sus-tain normal spermatogenesis. Similarly, sublethal geneticdamage to these surviving cells might produce an unaccep-tably high rate of malformation in offspring if sper-

matogenesis is preserved. Nevertheless, since D-Ieu6 GnRHand similar analogues are known to be non-toxic and to pro-duce mild and reversible alterations in spermatogenesis inman, it is reasonable to hope that their use will result inpreservation of reproductive function in patients who receivecytotoxic chemotherapy.We thank Emil Fret, III, for the stimulating discussion which led us to carry

out this study, Mrs Dianna Unitt for secretarial assistance, and Takeda-AbbottProducts for the D-leu" GnRH. This work was supported by the Maytag grantfrom the American Cancer Society, Denver Chapter.

Requests for reprints should be addressed to L. M. G., University ofColorado Health Sciences Center, 4200 East Ninth Avenue, B171, Denver,Colorado 80262, U.S.A.

DR GLODE AND OTHERS: REFERENCES

1. Schilsky RL, Lewis BJ, Sherins RJ, Young RC. Gonadal dysfunction is patients receiv-ing chemotherapy for cancer. Ann Intern Med 1980; 93: 109-14.

2. Chapman RM, Sutcliffe SB, Malpas JS. Cytotoxic-induced ovarian failure in womenwith Hodgkin’s disease. JAMA 1979; 242: 1877-86.

3. Rivier C, Rivier J, Vale W. Chronic effects of (D-Trp6, Pro9-NET) luteinisinghormone-releasing factor on reproductive processes in the male rate. Endocrinology1979, 105: 1191-201.

4. Heber D, Swerdloff RS. Male contraception: Synergism of gonadotropin-releasing hor-mone analog and testosterone in suppressing gonadotropin. Science 1980; 209:936-38.

5, Fairley KF, Barrie JU, Johnson W. Sterility and testicular atrophy related to

cyclophosphamide therapy. Lancet 1972; i. 568-69.6. Buchanan JD, Fairley KF, Barrie JU. Return of spermatogenesis after slopping

cyclophosphamide therapy. Lancet 1975; ii: 156-57.7. Roeser HP, Stocks AE, Smith AJ. Testicular damage due to cytotoxic drugs and

recovery after cessation of therapy. Aust NZ J Med 1978; 8: 250-548. Sherins RJ, Olweny CLM, Ziegler JL. Gynecomastia and gonadal dysfunction in

adolescent boys treated with combination chemotherapy for Hodgkins’s disease NEngl J Med 1978; 299: 12-16.

9. Etteldorf JN, West DC, Pitcock JA, Williams DL. Gonadal function, testicular

histology, and meiosis following cyclophosphamide therapy in patients with

nephrotic syndrome. J Pediatr 1976; 88: 206-12.10. Bergquist C, Nillius SJ, Bergh T, Skarin G, Wide L. Inhibitory effects on gonadotropin

secretion and gonadal function in men during chronic treatment with a potentstimulatory luteinising hormone analogue. Acta Endocr (Kobenhavn) 1979, 91:601-08.

11. Labne F, Auclair C, Cusan L, Kelly P, Pelletier G, Ferland F. Inhibitory effect ofLHRH and its agonists on testicular gonadotropin receptors and spermatogenesis inrat. Int J Androl 1978; 2: 303-18.

12. Savoy-Moore RT, Schwartz NB, Duncan JA, et al. Pituitary gonadotropin-releasinghormone receptors during the rat estrous cycle. Science 1980; 209: 942-44

13. Bourne GA, Regiani S, Payne AH, Marshall JC. Testicular GnRH recep-tors-Characterisation and localisation on interstitial tissue. J Clin Endocr. Metab1980; 51: 407-09.

14 Hsueh AJW, Erickson GF. Extra-pituitary inhibition of testicular function by luteinis-ing hormone releasing hormone. Nature 1979; 281: 66-67.

Reviews of Books

Antibiotic Therapy in Obstetrics and GynecologyRonald S. Gibbs, University of Texas Health Science Center, SanAntonio, Texas, and Allan J. Weinstein, Cleveland Clinic Foundauon,Ohio. Chichester and New York: John Wtley. 1981. Pp. 215. .IC. !20.

SEPSIS in obstetrics and gynaecology remains a substantial prob-lem despite a proliferating range of antimicrobials. In compilingthis practical guide, the authors skilfully combine extensive clinicalexperience with an appreciation of the principles of antibioticactivity and pharmacology. The title suggests that the emphasis isprimarily on antibiotic therapy, but the book in fact considersmanagement of infection in the broadest sense-it covers diagnosis,the pathogens, and, briefly, the relevant properties of individualantimicrobials. There is clear guidance about dosage and route ofadministration in relation to pharmacokinetic behaviour, and use inrenal failure and pregnancy. The latter part of the book discussesinfection in various sites, examining the role of antibiotics in

relation to other aspects of management, notably surgical inter-vention. These chapters are very much a synthesis of personalexperience and documented reports, enhanced by understanding ofthe activity and pharmacology of antibiotics, especially as applied toobstetrics and gynaecology. There are some examples of scientificimprecision, and occasionally unresolved matters are oversimpli-fied (for example, there is no persuasive evidence for preferringtobramycin to gentamicin on grounds of reduced toxicity, as theauthors suggest); such details are unlikely to matter in the context inwhich this book will prove useful. Results of recent studies ofinfections are evaluated concisely in discussion of each topic, butthere are no direct references, though a short reading list relevant toeach chapter is appended.The approach to anaerobes seems at times a little ambivalent-the

authors report that anaerobes are isolated from a proportion of

patients with postpartum sepsis, yet claim that their experience hasshown that 95% of patients with postpartum fever respond toampicillin and an aminoglycoside alone. In other words, adequatecover is usually achieved without the use of antibiotics active against

1135

anaerobes. They do stress the need for further evaluation of the roleof anaerobes and suggest that anti-anaerobic agents should be givento patients with serious infection, those who do not respond to otherregimens, or those with other infections such as postabortal sepsisor tubo-ovarian abscess where Bacteroides fragilis is a likelypathogen. Metronidazole is still not yet licensed for use in anaerobicinfection in the United States (though this may change shortly) andso the choice of agents is limited, essentially to clindamycin or chlor-amphenicol. Although in the United Kingdom metronidazole maybe used readily on empirical grounds (often justified since

laboratory diagnosis of anaerobic infection may be delayed), there isreluctance to use potentially toxic drugs such as clindamycin orchloramphenicol unless indications firmly justify their use.Other differences which British readers should appreciate include

the use of penicillin G as an oral drug, and of unfamiliarpenicillinase-stable penicillins such as nafcillin, which are notmarketed in Britain. The complicated issues of antimicrobial

prophylaxis are examined; the authors consider that prophylaxis ofhigh risk patients (such as those in labour, or with ruptured mem-branes) undergoing caesarean section is worthwhile, but that itsvalue in patients with prolonged ruptured membranes remainsuncertain. Infections in obstetrics and gynaecology are often mixed,and the principles of combined antibiotic therapy are thoughtfullydiscussed, with emphasis on the need to justify combinationsrationally.The book offers a well-balanced, circumspect guide to the

management of infection in obstetrics and gynaecology. Its format iswell organised and it may be readily referred to as a guide to drug usem everyday management; the latter part of the book provides a lucidcommentary on the diagnosis and management of infection, a usefulpreparation both for clinical practice and for the M.R C.O.G exam.

Department of Bacteriology,Queen Ehzabeth Hospital, Birmingham JANE SYMONDS

Angiography in TraumaA Work Atlas. Yoram Ben-Menachem, University of Texas, Philadelphiaand Eastbourne. W. B. Saunders. 1981. Pp. 476. 44.75.

THE idea behind this atlas was to provide an easy referencesuitable for radiologists already trained in angiography to enablethem to deal quickly with the problems which arise in the

emergency examination of seriously traumatised patients. As theauthor, a professor of radiology and director of a vascular radiologyunit, graphically puts it in the preface-the young radiologist,having mastered the technique and interpretative aspects of plannedangiography of scheduled daytime work, soon discovers that

Midnight Specials are orchestrated by a different conductor.After a useful chapter on how to perform angiography in trauma,

succeeding chapters deal with the mechanism of injury, blunttrauma, stab wounds, gunshot wounds, and shotgun wounds. In theshort section on iatrogenic trauma produced by various

angiographic procedures experienced angiographers will recognisemany of the examples given. One illustration, fig. 9-5, is said toshow rupture of the aorta during translumbar angiography, but theappearances seem to be identical with simple extravasation. Theauthor gives useful advice on the choice of procedure to be used andlays emphasis on the need to carefully consider the mechanism ofinjury and to relate this to the examination. For diffuse injuries herecommends what he calls the TBQ or "Total Body Quickie"procedure. This involves transfemoral catheterisation, followed bya series of films, with injection made (1) in the aortic arch, (2) in thelumbar aorta, and finally (3) just above the aortic bifurcation. Eachseries is taken without stopping to study the films until the wholeexamination is completed. Only after this is any form of selectiveprocedure carried out. With more localised injuries the need to takeangiograms in more than one plane is stressed. The need to extendfilmmg time up to 20 seconds is also underlined if importantmformation is not to be missed.The book has about one thousand figures, nearly all clear

reproductions of high quality radiographs. Much skill is required to

produce the calibre of the work illustrated. The author states that afour-vessel selective study of the head-and-neck of a young patientshould be possible in a few minutes and presumably this degree ofexpertise is available in his own department. However, only thelarger centres are likely to be able to provide staff of this standard.This admirable book is, therefore, likely to appeal mainly toradiologists working in highly specialised accident centres, but alltrainees would benefit from study of this book and most radiologistswould be glad to have it available if suddenly called upon to doangiography in a seriously injured patient.Department of Radiology,London Hospital R. S. MURRAY

Clinically Oriented AnatomyKeith L. Moore, University of Toronto, Ontario. Baltimore: Williams andWilkms. 1980. Pp. 1257.$28.25.

DESIGNED for use with Grant’s Atlas of Anatomy, this newtextbook contains illustrations from the atlas and is divided into ninecolour-coded sections depicting the regions of the body in the sameway as in the atlas. The text, which contains many useful andillustrative comments and references to clinical applications, hasbeen specially screened so that it is easy to pass over these if a

straightforward account of the anatomy is sought.The author has endeavoured plainly to continue J. C. Boileau

Grant’s tradition of clinically oriented methodic teaching of basicmedical science. He has set out to aid the hard-pressed pre-clinicalstudent to acquire an adequate knowledge of anatomy and make himor her realise that anatomy is the foundation of all branches ofmedicine. Texts like this help students to be less at a loss when theycome to examine patients after having been subjected to a basicscience course that allows inadequate time for a sound grounding inanatomy. The material in this generously illustrated volume is wellorganised and flows logically. The text is lucid and readable. DrMoore explains the meaning of the terms used so that the studentcan relate the words to the structures they describe, an importantitem for beginners presented with a vast new vocabulary togetherwith a large amount of factual information. The good illustrationsand photographs often demonstrating the relation of structure tofunction are supplemented judiciously with examples of normal andabnormal radiological anatomy.In order to stimulate students to learn, many clinical-care studies

in anatomy are given at the end of each chapter, followed byexplanations regarding the anatomy to be applied to the clinicalconditions and features. Care has been taken to present the clinicalillustrations and comment at a level that is suitable for "beginning"medical students and that assumes no clinical experience.Emphasis is placed throughout the text on living and surface

anatomy, urging the students to examine their own bodies tosupplement what to Moore is the only other effective way ofstudying anatomy-i.e., "at the dissecting table with a good teacher,where the parts may be seen, felt and dissected". One mightadd-with access to a text such as Moore has produced to help makesure of the wealth of fascinating, if sometimes confusing,information revealed by the study of anatomy.The book is provided with a good comprehensive index referring

both to text and illustration and a list of suggested further reading issupplied at the end of each chapter.

Department of Anatomy,Channg Cross Hospital Medical School,London T. W. GLENISTER

Progress in AnatomyVol. L Edited by R. J. Harnson and R. L. Holmes. Cambridge:Cambridge University Press. 1981. Pp. 250. 27.50.

Progress in Anatomy is a new venture by the Anatomical Society ofGreat Britain. Of the ten articles (each 20-30 pages long) four relateto the nervous system, reflecting the intense research activity inneuroscience; two are based on comparative anatomy (muscle by D.

1136

Allbrook, arteriovenous anastomoses by G. S. Molyneux and M. M.Bryden). The remainder are singletons: the conduction system ofthe heart (a classical light microscopical study by R. H. Andersonand S. Y. Ho); the functional anatomy of the kidney (D. B. Moffat),illustrating the interrelation of structure with function; a criticalevaluation of the fossil evidence relating to human evolution (B. A.Wood); a fascinating account of parthenogenetically derived

embryos as a model system for studying mammalian early develop-ment (M. H. Kaufman).Overall this volume provides an interesting mixture of topics, but

although the variety in content is justified the variable presentationindicates rather loose editorial control. The detailed account offactors affecting microtubule and microfilament organisation, withspecial reference to neurulation, lacks an overall view of the role ofthese cytoskeletal elements in cell morphology. Allbrook’s article onmuscle is broad but superficial, being a catalogue of facts con-taining interesting snippets; it gives little inkling of the recentadvances made in this active research area. The outstanding contri-bution is by C. G. Phillips, on the microarchitecture of the primatemotor cortex; lucidly presented, interesting and stimulating,conceptually provocative, it shows the path along which anatomy isprogressing-namely, the development of light and electron micro-scopical techniques with greater resolution which, combined withelectrophysiological probes, converge to bring into focus thefunctional anatomy of living tissues and ’their ultrastructural

components.To what extent does this volume achieve its stated aims "to

educate students, encourage graduates and enlighten colleagues"?The depth and restricted range of most of the articles cater for thegraduate with specialist interests rather than undergraduates.Colleagues would be advised to seek enlightenment on the topics onwhich they already have some expertise; it is not a book to be

"dipped into". However, for anyone with morphological leaningsthe new series is an encouraging and welcome sign that anatomy isalive, well, and progressing with vigour.Department of Anatomy and Embryology,University College London FRANCES LEFFORD

EEG Primer

R. Spehlmann, Northwestern University Medical School and EEGLaboratories, Veterans Administration, Lakeside Medical Center,Chicago. Amsterdam and New York: Elsevier/North Holland. 1981. Pp.473. Hardback, Dfl. 154,$75; paperback, Dfl. 74,$36.

THE burgeoning of books on clinical neurophysiology in the pastfew years reflects the broadening of the area made possible by rapidtechnological advances and the contribution of basic scientists.Gloomy ideas that EEG would be superseded rather than

supplemented by modern imaging techniques happily have beenunfounded. Professor Spehlmann is a neurologist and director ofEEG laboratories in Chicago, and his book follows in the Americantradition of large, horizontally elongated atlases on

electroencephalography. This one has a handsome style and a coverwhich is distinguished graphically but which defies some EEGconventions. The atlas approach is embellished by a substantial textwith excellent tabulation of certain phenomena. It is written mainlytor beginners in EEG, in which group are included neurologyresidents, medical students, neuroscientists, and EEG technicians.Spehlmann states that he has started with simple concepts which arebuilt up in steps of increasing detail so that the reader can choose atwhat depth to master each topic. The description of clinicalcorrelates of EEG phenomena reverses the conventional order oflisting diseases or disease groups and then describing the associatedEEG abnormalities. Instead, descriptions of groups of EEG

patterns are followed by long and often repetitive lists of all theclinical conditions in which they might occur. After all Piaget’swork, it is rather startling to encounter a didactic textbook tendingto long lists for learning by rote rather than encouragement to think.Such an approach has the tang of arrogance for which the medicalprofession is so often castigated nowadays. A didactic, authoritativestyle can provide a systematic and disciplined basic education andsome readers will undoubtedly find that Professor Spehlmann’s

approach suits them well. But precise measurement techniques,data processing, clinical relevance and validity of correlations, mter-observer reliability, and audit of performance are today’s ideals andthe beginner needs enthusiastic instruction in these too. Severalmore orthodox, broader based, cheaper texts are available and thereader, looking for an introduction to clinical neurophysiology,would be well advised to compare them critically with this volumeto see which best suits his particular needs.

Department of Neurological Sciences,St. Bartholomew’s Hospital, London PAMELA F. PRIOR

A Handbook of Obstetrics and Gynaecology for the HouseSurgeon

By Mary M. Anderson, Lewisham Hospital, London. London: Faber andFaber. 1981. Pp. 173. 3.95.

THIS handbook attempts to provide a source of practical guidancefor the obstetric and gynaecological house officer in antenatal,intrapartum, and postpartum problems, and in outpatient andinpatient gynaecological care; the difficulty is how to select

appropriate advice for such a book when house officers work withdifferent levels of supervision and in units with different policies.There are liberal exhortations to consult senior colleagues and readstandard texts; but there is also advice to take some action whichwould usually be considered out of the province of the houseofficer-for example, to "give Dexamethasone to the mother if apremature infant is expected" (p. 35). The book is outdated in somerespects (it is distressing in 1981 to find the old definition of

"prematurity"—less than 2500 g-being used on p. 95) and there issome repetition (e.g., management of eclampsia).However, many sections of the book are useful. The section on the

postnatal ward is concise and well ordered except that it does notmention the possibility of disease, such as appendicitis, which isunrelated to the pregnancy. The section on neonatal care will proveuseful, as will that on social and legal aspects (except that it is

implied that necropsy would be arranged for a stillbirth only if nodoctor or midwife were present at the birth).

Overall, the book should prove useful to house officers workingwithout much supervison, but where adequate supervision isavailable the house officer would be better advised to discuss

practical management with senior colleagues and to consultstandard texts for theoretical background.Aberdeen Maternity Hospital MARION H. HALL

Handbook of Clinical Nutrition

R. L. Weinsier and C. E. Butterworth, University of Alabama ft)

Birmingham. St Louis: C. V. Mosby. London: Year Book MedicalPubhshers. 1981. Pp. 231. 8.25.

THERE is a real need for a concise handbook of clinical nutritionbut this volume does not fill the gap completely. The book dealswith nutritional assessment, the practical aspects of tube andparenteral feeding, and the nutritional management of specialclinical situations ranging from renal failure to obesity. The sectionson nutritional assessment and the general approach to nutritionalsupport contain helpful tables and advice on calculatingrequirements but the tables on food sources of major vitamins andminerals contain too much detail. The attempt to be too

comprehensive results in many very brief and dogmatic sections onquite complex and controversial subjects. The nutritional problemsof diabetics receive less attention than those associated with

vegetarian diets. The terminology and products listed indicate thatthe book has been written for North American readers. The almostexclusive use of North American references and the failure to use SIunits will alienate any potential European readers. This book ismore an introduction to the scope of clinical nutrition than aneffective practical handbook for day to day use.

Department of Surgery,University of Newcastle upon Tyne IVAND.AJOHKSTOX