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skin is irrelevant for the purpose of this paper. The significantfact is that the cell line with the + 21 was the one in which theuncontrolled blast cell proliferation occurred; the

disappearance of the leukaemoid reaction paralleled thedisappearance of the + 21 cells from the bone marrow.

CONCLUSION

The data presented here indicate that a gain of chromosomeno. 21 occurs in the leukaemic cells of constitutionally normalindividuals, particularly children with ALL, in whom + 21was seen in 19%. The presence of an extra no. 21 in DSchildren puts them at an increased risk of acute leukaemia,which is lymphoid in 70% of the cases. Finally, newbornswith classic DS, as well as newborns with no phenotypicfeatures of DS who have a mosaic karyotype including +21,may show an uncontrolled proliferation of blast cells, usuallymyeloblasts, with a maturation arrest that is of limitedduration and regresses spontaneously without

chemotherapy. This syndrome has been described as

ineffective regulation of granulopoiesis masquerading as

congenital leukaemia. 1 Thus a + 21 in DS appears to be apredisposing factor in the development of acute leukaemia,analgous to the chromosome deletions that carry an increasedrisk of the development of retinoblastoma or Wilms tumour.On an interpretation of these data according to the two-mutation hypothesis of Knudson,18 the presence of +21would be one mutation present in all cells with only one moremutation in a haematopoietic cell required to induceleukaemia. The increased risk of tumour development is

substantially greater in the abnormalities associated with aconstitutional deletion than in DS, and this is unexplained.Thus, a third of patients with a deletion including 11 p 13 andaniridia will develop Wilms tumours, whereas for a DS child,,the risk of leukaemia is estimated at 1 in 9519 compared with 1in 2880 for U.S. White children less than 15 years ofage.2O

It may be significant that a structural rearrangementinvolving the centromere-short arm region of no. 21 was seenin 1 of our 3 DS patients with leukemia, in both DS neonateswith a transient leukaemia whose cells were studied with

banding, and in 1 of the 2 phenotypically normal individualswith a leukaemoid reaction and transient trisomy 21. In 3 ofthe 4 cases; the rearrangement was a t(21;21), and in thefourth, it was a t(21;22). As is the case for the chromosomedeletion syndromes, the genes on chromosome 21 that areassociated with leukaemogenesis when the chromosome ispresent in triplicate are presently unidentified.

I thank Dr Harvey M. Golomb and Dr Yasuhiko Kaneko for helpfuldiscussions. This work was supported in part by U.S. Public Health Servicegrants CA-16910 and CA-25568 awarded by the National Cancer Institute andby the Department of Energy, no DE-AC02-80EV 10360.

REFERENCES

1 Krivet W, Good RA. Simultaneous occurrence of mongolism and leukemia: Report of anationwide survey. Am J Dis Child 1957; 94: 289.

2. Conen PE, Erkman B. Combined mongolism and leukemia. Report of eight cases withchromosome studies Am J Dis Child 1966; 112: 429.

3 Miller RW Neoplasia and Down’s syndrome. Ann NY Acad Science 1970; 171: 637.4. Yunis JJ, Ramsay N. Retinoblastoma and subband deletion of chromosome 13. Am J

Dis Child 1978; 132: 161-63.5. Riccardi VM, Sujansky E, Smith AC, Francke U. Chromosomal imbalance in the

aniridia-Wilms’ tumor association: 11p interstitial deletion Pediatrics 1978; 61:604-09.

6 Fraumeni JM, Glass AG. Wilms’ tumor and congenital aniridia JAMA 1968; 206:825-28

7. Balaban-Malenbaum G, Gilbert F, Nichols WW, Hill R, Shilds J, Meadows AT. Adeleted chromosome no. 13 in human retinoblastoma cells. Relevance to

tumorigenesis. Cancer Genet Cytogenet 1981; 3: 243-50.8 Kaneko Y, Eques MC, Rowley JD. Interstitial deletion of 11p limited to Wilms’ tumor

cells in a patient without aniridia Cancer Res (in press)

9. Third International Workshop on Chromosomes in Leukemia: Chromosomeabnormalities in acute lymphocytic leukemia Cancer Genet Cytogenet (in press)

10. Rowley JD, Testa JR. Chromosome abnormalities in malignant hematologic diseasesAdv Cancer Res (in press).

11. Kaneko Y, Rowley JD, Variakojis D, Chilcote RR, Moohr JW, Patel D. Chromosomeabnormalities in Down’s syndrome patients with acute leukemia Blood 1981, 58:459-66.

12. Rosner F, Lee SL. Down’s syndrome and acute leukemia Myeloblastic or

lymphoblastic? Am J Med 1972; 53: 203-18.13. Rogers P, Denegri JF, Thomas JW, Kalousek O, Gillen J, Baker MA Down’s

syndrome-leukemia versus pseudoleukemia Blood 1978; 52: 27314. Lazarus KH, Heema N, Palmer C, Bachner RL. Transient myeloproliferative reaction

of Down’s syndrome: Chromosomal, cytomorphological and clinical evidence for amalignant origin. Proc Am Assoc Cancer Res 1981; 22: 44

15. Brodeur GM, Dahl GV, Williams DL, Tipton RE, Kalwinsky DK. Transientleukemoid reaction and trisomy 21 mosaicism in a phenotypically normal newbornBlood 1980; 55: 691-93.

16. Heaton DC, Fitzgerald PH, Fraser GJ, Abbott GD. Transient leukemoid proliferationofthe cytogenetically unbalanced + 21 cell line of a constitutional mosaic boy Blood1981; 57: 883-87.

17 Ross JD, Moloney WC, Desforges JF. Ineffective regulation of granulopoiesis.masquerading as congenital leukemia in a mongoloid child J Pediat 1963; 63: 1 -10

18. Knudson AG. Mutation and cancer: Statistical study of retinoblastoma. Proc Natl AcadSci 1971; 68: 820-23.

19. Barber R, Spiers P. Oxford survey of childhood cancer. Progress report II. Mon BullMm Health 1964; 23: 46-52.

20. National Center for Health Statistics. Vital statistics of the United States, annual

report, 1964. Washington, DC: US Government Printing Office

Reviews of Books

The First Year of Life

Library of General Practice, Vol. Il. Graham Curtis Jenkins, Ashford,Middlesex, and Richard Newton, Ashford Hospital, Middlesex.

Edinburgh: Churchill Livingstone. 1981. Pp. 275. 8.50.

WHEN Prof. Donald Court called for general practitionerpaediatricians (Court Report, 1976) the precedent had already beenset by Graham Curtis Jenkins and others. Although most of theircolleagues do not accept the principle of specialisation withinpractice, many may want to develop their skills in child care or tokeep abreast of some of the recent developments in this area. Forthem this paperback is useful. It presents persuasively the case forincreasing general practitioner involvement in the surveillance,assessment, and care of the young child, and gives a succinct resumeof some of the more common and a few of the less commonconditions encountered in this age group. Here is an easy volume to

pluck from the shelf when some light is required on, for example, anunfamiliar condition mentioned in the hospital discharge letter.The way those early problems such as vomiting, the crying baby,

irritability, and restlessness are discussed reflect sensitivity to thepatient’s needs, and the concept of "family morale" is placed firmlyin the context of sympathetic general practice. Writing from thecomfortable home counties, however, the authors can only touch onthe problems of the inner cities and of those northern areas wherethe problems are daunting indeed. I vividly recall my days as, a

junior at the Liverpool Children’s Hospital, Liverpool 8, when theprocession of minor problems brought general practice into casualtyafter 5 P.M. In discussing inner city practice the authors mention thework of Prof. J. L. Emery and his colleagues in Sheffield who, withthe aid of health visitors, concentrate on an identified "at risk"underprivileged section of the population and have thereby reducedthe infant mortality rate.

Jenkins describes his own developmental surveillance system aswell as the classical Dubowitz and Gesell schedules, and gives aclear account of the first examination of the newborn, including theearliest assessment of sighted, hearing, and social responses. Breastfeeding and bonding also are well covered, and in a short but usefulchapter on immunisation the authors pick their way, with muchcommon sense, through the well-known pros and cons of

conflicting, and sometimes contradictory, recommendedimmunisation programmes. The chapter on paediatric prescribingin the first year of life is informative. How soon will it be, I wonder,before the public realises the utter futility of giving young children

1023

cough suppressants which cause only sedation and often increaseirritability? More prominence could perhaps have been given to theevents which can send the greatest shock waves through anypractice-namely, child abuse and the sudden infant death

syndrome (cot death). Both these problems now must be consideredamongst the common causes of infant mortality, and although thescale of morbidity caused by child abuse can only be surmised, itmust be considerable.For students preparing for higher examinations this book is a

good’starting point, but it is unfortunate that the publishers haveomitted the further reading list promised. The section containingmultiple choice and essay questions at the end is helpful. Manyolder practitioners who did not enjoy the benefit of a paediatrichouse job may also find this book useful.The sentiments of many of us on bereavement and stillbirth

would echo those of the authors, and few can express them betterthan Shakespeare:

"Give sorrow words: the grief that does not speakWhispers, the o’erfraught heart and bids it break".

Department of Paediatrics,Worcester Royal Infirmary A. P. COLE

Fundamentals of Colitis

S. J. M. Goulston and V. J. McGovern, Royal Prince Alfred Hospital,Sydney. Oxford and New York: Pergamon Press. 1981. Pp. 133. f5,$10.50 (paperback); ;E8.50,$18 (hardback).

THE series "Fundamentals of ... " is aimed not only at prac-titioners with a special interest but also at general practitioners and,in particular, medical students. It is said to bring together clinicaland pathological points of view in works which are comprehensivein a practical way. If the whole of its first volume is allocated to theadmittedly important subject of colitis, I wonder how many subjectsand books are likely to be necessary for the general practitioner ormedical student who wishes to cover the whole of medicine ? A book,however short, on a special subject and aimed at generalistsimmediately arouses my suspicion-what are general textbooks for?Having stated my prejudices I must immediately add that much of

this book is good. It is very well illustrated with black and whitepictures of histological sections and radiographs. It emphasises theinfective causes of colitis at a time when ulcerative colitis andCrohn’s disease are so well known that other diagnoses risk beingmissed or delayed. The authors can be congratulated on the fullnesswith which they treat their subjects within the strait-jacket of thebrevity imposed upon them. But who will read this short,reasonably up to date, and fairly comprehensive account of colitis?Medical students and general practitioners will find it too detailedand may well prefer a textbook. The specialist will find it containsnothing new and is too brief. The specialist in training may find ituseful but will quickly discover that the references are inadequate(for example, three out of the six references about ulcerative colitisare concerned with the interesting but small increase in cancer risk).The book will be most useful to the general physician, and if itsucceeds in reminding him of the importance of the infective causesof colitis and serves as a warning of the dangers of underestimatingthe severity of acute ulcerative colitis, it will riot have been writtenin vain.

Gastrointestinal Unit,Charing Cross Hospital, London JEREMY POWELL-TUCK

SchizophreniaJohn Strauss, Yale University School of Medicine, New Haven, Con-necticut, and William Carpenter, University of Maryland School ofMedicine, Baltimore, Maryland. New York and London: Plenum. 1981.Pp. 220.$22.50.

THIS attractively produced book is designed to be "a readableexposition of value to clinicians, investigators and clinicaladministrators." A multifactorial approach to the aetiology,diagnosis, and management of schizophrenia, and the importance ofapproaching each patient as an individual are firmly advocatedthroughout.An early chapter proposes an "interactive developmental systems

model" of aetiology, in which the interplay of genetic

predisposition, perinatal complications, and impaired mother-infant "bonding", lead to vulnerability to schizophrenia whilesubsequent stress, which may be psychological, social, or biological,precipitates the illness. There follows a useful review of differentdiagnostic criteria, including those of Kraepelin, Bleuler,Schneider, the Research Diagnostic Criteria, the International PilotStudy of Schizophrenia, and DSM-III. The authors comment onthe inadequacies of any diagnostic system which relies on

symptomatology alone and favour a multiaxial system whichconsiders the course of the disorder, associated life events, socialfunction and work function, and presenting symptomatology. Achapter called "Beyond Diagnostic Criteria" emphasises the

importance of appreciating the individual patient’s subjectiveexperiences, but there is only a scant account of the phenomenologyof schizophrenia. There are short chapters on prognosis andepidemiology, then a full and clear review of the main biological,social, and psychodynamic theories of aetiology and their

experimental background. The section on treatment concentratesmainly on psychological and social aspects and includes an

interesting section about the role of psychotherapy in

schizophrenia. Somatic treatments are considered more briefly, andonly general principles of drug therapy are discussed. The finalchapter concerns legal aspects of the disorder; violence to others isconsidered here and elsewhere in the book, but there is no mentionof the dangers of suicide or self-harm. Each chapter has a shortreference list and there is an adequate index.The book gives a balanced account of its subject and contains

much clinical wisdom, much of which is applicable to the

management of any mental or physical illness. I find the stylesomewhat discursive in parts and think that a fuller factual content-for example, a description of the drugs used in treatment-wouldbe an improvement. Schizophrenia, Towards a New Synthesis (editedby J. K. Wing, Academic Press, London, 1978), which is similar inlength and price, contains greater detail and more critical evaluationof research on schizophrenia, but Strauss and Carpenters’ bookprovides a more easily read general review.

Department of Psychiatry,University of Southampton JENNIFER HUGHES

Tropical GastroenterologyG. C. Cook, University of Papua New Guinea. Oxford: Oxford UniversityPress. 1981. Pp. 484. ;[20.

Dr Cook has had more than 12 years’ varied experience of hissubject in East, Central, and West Africa, Saudi Arabia, and NewGuinea. His philosophy is that since medicine is the same the worldover-with some geographical variation-"tropical medicine"should not be partitioned off, as it were, from general medicalexperience.His comprehensive account of tropical gastroenterology begins at

the lips and completes its traverse of the alimentary system 444pages later at the anus. Despite the logical, anatomical sequence ofthe chapters, the text is so detailed and refers so much to all possiblyrelevant literature that it is advisable to leave adequate intermissionsbetween the readings of individual chapters in which to digest eachsolid course.A fascinating review of the distribution and possible causes of

carcinoma of the oesophagus precedes a massive chapter on diseasesof the stomach and duodenum which gives 7 pages to duodenalulcer. From this one learns that peptic ulceration is less rare intropical Africa than formerly supposed, its incidence in Nigeria is ashigh as that in South India, and the condition is common in PapuaNew Guinea. The authorities cited number some 125, which gives afair idea of the comprehensiveness of Cook’s coverage of theliterature.The section on the liver and biliary system takes up a third of the

book, which is a just tribute to the importance of this system intropical medical practice. An explanation of the stresses and noxiousfactors to which the liver in the tropics is exposed is followed by aninformative essay on the histopathological effects of parasitic andbacterial infection. Viral infections are reviewed in detail and with

great clarity. Hepatitis A and B viruses are widely distributed

1024

among tropical peoples, yet most examples of acute hepatitisare attributable to a non-A, non-B agent (or agents), as yetundefined. Even so, it is estimated that 3007o of the tropicalpopulation carry antibodies to hepatitis B surface antigen while20% are chronic carriers of the infecting agent itself. The possibleimportance of blood-sucking insects in transmission has yet to beassessed. The hepatitis B antigen and probably the third agent causechronic active hepatitis, which leads to cirrhosis and hepatoma,which is the liver disease of paramount importance in the tropics.Cook uses the term post-infective tropical malabsorption instead

of tropical sprue, but it seems a pity to abandon a name hallowed bytradition, especially since it has not been proved that all cases areinfective in origin. He notes that steadily increasing numbers of thissyndrome are being recognised in Africa, but these seem to carry alow case-mortality by Asian standards.Cook has done much research into hypolactasia. A high lactase

content of the brush borders of the jejunal cells, persisting into adultlife, seems to be genetically controlled. It is common in European,Middle Eastern races, Pakistanis, and Hamites, but is rare in

Negroes. However, hypolactasia does not inevitably lead to

diarrhoea on drinking much milk, and its clinical importance isuncertain. Secondary hypolactasia follows any condition whichdamages the enterocyte and may persist long after apparentrecovery.In discussing cholera, Cook does not give the prominence it

deserves to the dramatic surge of the El Tor vibrio from Chinawestwards to reach Spain and West Africa since 1960, or to thebiological properties of this enterprising vibrio which determine itsepidemiology; but treatment is very well described. The account ofabdominal tuberculosis is most impressive and indicates the pitfallswhich may trap clinicians in Britain who deal with immigrants fromthe tropics. Cook also describes Burkitt’s lymphoma, thecommonest tumour of the small intestine, and mentions the

recently described but somewhat indefinite condition designatedMediterranean lymphoma. The point is well made that in the U.K.intestinal amoebiasis may be misdiagnosed as ulcerative colitis andthat steroid therapy may be given with disastrous, possibly fatal,results. A full review of the disease, its diagnosis, complications, andtreatment is given, but a more didactic approach to specific therapymight be appreciated by physicians unversed in this disease. Thesame can be said of the otherwise excellent chapter on intestinalschistosomiasis.This review cannot do justice to the erudition and tremendous

industry displayed in this book, which constitutes a world-widesurvey of a vast subject. All chapters have long reference lists, and itis as a reference book rather than as a textbook that this volumeshould be regarded, for the author rarely reveals his own preferencewhen discussing alternative lines of treatment. The illustrations, allin black and white, are, unfortunately, not impressive, and one toillustrate anaemia in a Zambian woman inevitably fails in its object.Even amid such referential fertility I am delighted to find mention

of a paper on therapy in opisthorchiasis published in the ChinaMedical Journal (l965) by Wang, Chung, Shen, Huei, Chou, Hsu,Chao, Wu, Lan, Ts’ao, Cheng, Li, Cheng, and Sung. Is this a worldrecord in collective medical authorship?

Higher Lawn, Chudleigh,Newton Abbot, South Devon JOHN WALTERS

Haemostasis and Thrombosis

Edited by Arthur L. Bloom, Welsh National School of Medicine, Cardiff,and Duncan P. Thomas, National Institute for Biological Standards andControl, London. Edinburgh: Churchill Livingstone. 1981. Pp. 868. :E35.

SINCE the study of the contribution of blood factors to vasculardiseases involves biochemistry, physiology, pathology,haematology, general medicine, and epidemiology, haemostasis andthrombosis cannot be allocated exclusively to any of these

specialties; also, they cannot be dealt with entirely separately. Thisyear sees two major attempts at integration-firstly, the formationof the British Society for Haemostasis and Thrombosis, and,secondly, this volume. The editors have undoubtedly succeeded intheir aim for a medium-sized, reasonably comprehensive textbookcovering haemostasis and its disorders as well as thrombosis. Thefifty logically arranged chapters cover all aspects of platelet

function, coagulation, and fibrinolysis, including interactionsbetween platelets and blood vessels and the role haemostasis plays ininflammation (16 chapters); bleeding disorders, including those inthe pregnant and the newborn (12 chapters); the epidemiology andpathogenesis of thrombosis and atherosclerosis (9 chapters); thediagnosis and management of thrombosis (7 chapters); and theprinciples of laboratory assessment of haemostatic factors (6chapters). The authors are all expert, and their reviews are readable,well-illustrated, and up-to-date. There is little overlap, andomissions are few.The book can be recommended to all haematologists, and to all

clinicians interested in vascular disease. It also deserves a place in allgeneral hospital libraries; in all medical, surgical, obstetric, andpaediatric units; and in all departments of biochemistry,physiology, and pathology. It will repay its cost well into the

eighties, when developments will surely make a second editionnecessary.

University Department of Medicine,Royal Infirmary, Glasgow G. D. 0. LOWE

Valvular Heart Disease

Edited by James E. Dalen and Joseph S. Alpert, University ofMassachusetts Medical School, Boston: Little Brown. London: Quest.1981. Pp. 473.$31.75. 21.27.

A TEAM from the University of Massachusetts Medical School hasproduced this comprehensive compilation of facts on valvular heartdisease with reference to articles published as recently as 1980.Problems of multiple authorship have been avoided in the main, buta glaring exception is hypertrophic obstructive cardiomyopathy,which is discussed twice in detail, once with a plea to accept the termhypertrophic cardiomyopathy, and again under the title of

idiopathic hypertrophic subaortic stenosis.The pathophysiology, clinical features, investigation, and

management of individual valve disorders are discussed logicallyand competently, with special emphasis on the timing of surgicalprocedures. The chapters on acute mitral and aortic regurgitationare particularly valuable. It is disappointing that there is noreference to Doppler techniques, and the descriptions of

echocardiographic findings are often presented as though the onlyimportant features are derived from M mode recordings. Referencesto cross-sectional echocardiography are perfunctory and oftenuninformative. In particular, the value of cross-sectional

echocardiograms in defining the site of left ventricular outflow tractobstruction and in acute mitral regurgitation deserve more

attention; and illustrations to emphasise the 2D echocardiographicappearance of the vegetations of infective endocarditis, and thedemonstration of tricuspid reflux by the use of contrast andsubxiphoid views would enhance discussion of these topics.The chapter on anticoagulants would be improved by an

expanded section on antiplatelet drugs, and the list often eponymsfor the peripheral signs of aortic regurgitation seems curiouslyoutdated in a modern book. The recommendations for prophylacticregimens in infective endocarditis are presented uncritically. It isalmost impossible to ensure that intramuscular penicillin is givenhalf an hour before dental procedures, and even less likely thatintravenous vancomycin would be practical for penicillin-sensitivepatients.Success in presenting a comprehensive account of valvular heart

disease is not necessarily compatible with the author’s stated aim offilling a long-standing gap in the literature. A major textbook ofcardiology covers the same ground, and should give better value ifthe extra expense can be accommodated.

Department of Medtcine, ,,Royal Lancaster Infirmary A. K. BROWN

New Editions

Basic Pharmacology in Medicine.-By Joseph R. DIPalma, New York:McGraw-Hill Book Company. 1981. Pp. 517.$25.

EEG Technology.-3rd ed. By R. Cooper, J. W. Osselton, and J. C. ShaBB.Sevenoaks, Kent: Butterworths. 1980. Pp. 344. 16.

Primer for the Psychotherapzst.-2nd ed. By Joyce A. Bockar. LancasterM.T.P. Press Ltd. 1981. Pp. 149. jE8.95.