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Immunological reactions between the host and graft arecomplicated by the large quantity of organised lymphoidtissue within the graft. Eight weeks after SBT graftlymphoid tissue was largely but not completely replaced bycells of host origin. Host-versus-graft reactivity has beendemonstrated in both host and graft lymph nodes within 24hours of allogeneic transplantation. Local immunologicalresponses may hamper the small bowel’s barrier functionagainst pathogenic organisms. Widespread bacterialtranslocation into host tissues takes place during acutesmall-bowel rejection in rats but does not occur when

rejection is prevented by cyclosporin. Significant bacterialovergrowth has also been demonstrated in the host intestineduring GVHD. Thus it appears that the emergence of

rejection or GVHD poses a major threat from

overwhelming bacteraemia.In other organ transplants cytokines have an important

role in rejection and GVHD, and a correlation has beenshown between serum levels of tumour necrosis factor

(TNF) and the development of GVHD after SBT in rats.Anti-TNF antiserum has been shown to alleviate mildGVHD and prolong graft survival.The intense immunogenicity of a small-bowel graft is a

major reason why SBT fares poorly compared with otherorgan grafts. Environmental factors contribute to this

immunogenicity. Crypt epithelial cells in rat intestine

normally express major histocompatibility complex (MHC)class II antigens. However, if the rats are reared in a specificpathogen-free environment, class II expression does notoccur until the small bowel is explanted and subjected tocold ischaemia. MHC matching between donor and host isclearly important: in dogs, MHC matching combined withcyclosporin treatment allowed long-term small-bowel

allograft survival (> 200 days), compared with rejection in 9days in controls. Graft immunogenicity has been

successfully reduced by means of pretreatment with anti-MHC class II monoclonal antibodies, and this has led to asignificant prolongation of graft survival time.

Better immunosuppressive drugs may give a new impetusto clinical SBT. Cyclosporin and FK 506 have shownsimilar effects in preventing rejection, but FK 506 allowedthe development of a sometimes lethal GVHD. Both FK506 and the new agent RS 61443 could reverse establishedsmall-bowel allograft rejection, whereas cyclosporin couldnot.

Of 128 patients on the UK Home Parenteral NutritionRegister, 45 were considered suitable for transplantation.Diagnoses considered favourable for transplantationincluded mesenteric vascular disease, pseudo-obstruction,radiation enteritis, volvulus, gastroschisis, familial

polyposis, desmoid tumours, necrotising enterocolitis, andmotility disorders. Patients whose disease was potentiallyself-limiting (eg, anastomotic dehiscence), potentiallyprogressive (Crohn’s disease), or terminal (carcinoma) werenot considered suitable for SBT.

Clinical SBT has met with only sporadic success to date,and a French group has decided to halt its paediatrictransplant programme. Of seven children transplanted inParis so far, rejection had developed in six, and only oneinfant had a long-term ( > 2 years) functioning graft.Multiorgan transplantation may reduce the risk of rejection.For instance, sequential liver and small-bowel

transplantation in rats led to survival of over 100 days,compared with controls (SBT alone), in which rejectiondeveloped at 9 days. Multiorgan transplantation does not,

however, reduce the risk of (possibly fatal) GVHD in rats.Monitoring of multivisceral transplants is not easy becauserejection within different organs is variable. Rejection wasmore aggressive in the small bowel than in the stomachafter combined pancreas, stomach, and small-bowel

transplantation.Most EITSG members thought that further advances in

immunosuppressive therapy, specific immunomodulation,and the development of a more reliable method of graftmonitoring were necessary before a clinical SBT

programme should be undertaken. However, groups in Kieland Uppsala would consider using SBT as a last resort inpatients whose clinical condition while they were on totalparenteral nutrition was deteriorating. The EITSG is nowtrying to identify patients in Europe with irreversiblesmall-intestinal failure in the expectation that SBT willbecome more successful in the next few years.

R. L. MarquetC. L. Ingham Clark

We are what we eat

We all know about the harmful effects of poor dieton health, but does the way we were fed in infancypredispose us to disease many years later? This questionwas the theme for the British Nutrition Foundation’s 13thannual conference, Early Diet, Later Consequences, held inLondon on June 14. Although numerous studies haveaddressed the topic, there are few signs that the gaps in ourknowledge are narrowing, not least because many of thestudies are beset with methodological and designdifficulties. Most trials in developing countries, for

instance, have been largely observational, retrospective,confounded by unfavourable social circumstances, and notproperly controlled. The results of retrospective studies indeveloped countries have been inconsistent, and only ahandful of the few prospective studies done have beenrandomised.

What, then, is the evidence for a detrimental effect of poorearly nutrition on health? In a cohort of stunted Jamaicanchildren Dr Sue Grantham-McGregor (University of

Jamaica) found that early malnutrition led to poor mentaldevelopment, as evidenced by the benefit conferred bynutritional supplementation with and without psychosocialstimulation. Whether this finding is due to changes in thecentral nervous system, in child activity, or in maternalresponsiveness is, however, unclear. The "programming"hypothesis, in which a stimulus or insult operating at acritical period of development (but harmless at any othertime) leads to long-term effects on structure and functionof an organism, was invoked to account for such effects:Dr Alan Lucas (MRC Dunn Nutrition Centre) suggestedthat this critical "window" in time occurred (thoughnot exclusively) in the first few weeks of life. His datafrom an ongoing long-term prospective study on preterminfants randomly assigned to various diets (breast milk,standard term formula, or preterm formula) show thata 1-month postnatal dietary manipulation has serious

consequences for motor and mental development, bonemineralisation, allergy, and growth at age 9 and 18 monthsand 5 and 7-8 years. Prof David Barker (MRC

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Environmental Epidemiology Unit, Southampton) madethe startling suggestion that the critical window forcardiovascular disease could occur even in fetal life, sincefeatures of disease in middle age (eg, high blood pressure)were associated with higher placental weight relative tobirthweight.The role of dietary programming in later obesity was

questioned by Dr Elizabeth Poskitt (University of

Liverpool), who suggested that fat infants may not consumemore than slim infants but have lower energy expenditure.Genetic factors, she thought, may be much more importantthan metabolisable energy intake in determining fatness. DrDavid Forman (ICRF Cancer Epidemiology Unit, Oxford)pointed out that although it is entirely plausible that earlydiet could lead to later cancer, few studies have providedsatisfactory supportive evidence, largely because of thenumerous foods thought to be associated with cancer

aetiology and because of the difficulties in obtaining reliabledietary information. An exception is the well-knownassociation in Chinese populations of nasopharyngealcarcinoma with consumption of salted fish. Dr AndrewCant (Newcastle General Hospital) concluded that geneticand immunological predisposition, as evidenced byfamily history of allergic diseases and total cord blood IgE,are the most important determinants of allergic disease,and that diet is important only in these high-risk babies.Finally, Prof Brian Wharton (Glasgow University)considered the possible role of breastfeeding on the laterdevelopment of coeliac, Crohn’s, and inflammatory boweldisease. A possible mechanism is that in a geneticallypredisposed individual, breastmilk modifies the gut’sexperience of foreign antigens (microbiological or chemical),a subsequent environmental stimulus then leading to

disease.The message of the day was that there is now tantalising

evidence that diet in infancy could have far-reaching effectson health in adult life and important implications for theprevention and management of many diseases.

The conference proceedings will be published as a supplement to the BNFBulletin in the autumm of 1991.

The Lancet Pia Pini

Medicine and the Law

Worried obstetricians

On June 11 the president of the Royal College ofObstetricians and Gynaecologists, Mr Stanley Simmons,introduced Childbirth 1991 as a symposium held in

response to the Royal College’s concern about negligenceclaims for brain-damaged babies. The RCOG wished tohave a dialogue with people outside the specialty. Its ownviewpoint was that an unjustified increase in negligenceclaims was putting obstetrics in the UK at risk-and at atime when perinatal and maternal mortality rates had neverbeen lower. Figures cited at the meeting indicate thatperinatal mortality was 32 per 1000 in 1958 but had fallen to8 per 1000 in 1990; maternal mortality in 1948 was 133 per100 000 and is now 7 per 100 000. The RCOG argument isthat there is little evidence that management of labour hasbeen responsible for most cases of cerebral palsy. ProfGeoffrey Chamberlain, chairman of the Joint Medico-Legalcommittee of the RCOG/Defence Societies, ascribed the

general improvement in perinatal statistics to a combinationof factors-roughly two-thirds better education, nutrition,and health of mothers and one-third advances in obstetric

management and medical knowledge and equipment. Yetthese factors had made no impact on the numbers of babiesborn with cerebral palsy who survived. It should also benoted that improved neonatal care has enabled far moreseriously handicapped babies and premature babies to

survive than was possible 20 years ago.An RCOG survey has revealed that 85% of obstetricians

in Britain have had at least one legal claim against them andthat 65% have had two. There is also concern thatrecruitment is down because, as one student put it toProfessor Chamberlain, obstetrics brings with it too much"hassle" and lawyers seem to have too great an input inobstetric practice. At the other end obstetricians are leavingthe specialty early; the average retirement age has fallen from65 to 58, possibly in part because of this medicolegalsituation.The concerns that need to be addressed include the virtually

unlimited time allowed in law for brain-damaged persons to mountclaims and the problems that these stale claims cause; and theadversarial system with its slowness, expense, uncertainty ofoutcome, and bitterness generated between parties once in so close arelationship but now adversaries. At the symposium lawyers, whohad represented both sides, admitted that the system was imperfect,but one barrister thought that no-fault compensation wouldfounder on the establishment of causation for the purposes of

compensating a brain-damaged child if the criteria were error ofjudgment or avoidable injury. Sir Donald Acheson, from theDepartment of Health, said that he would like to see a change in theway that compensation cases are assessed. There was a consensusamongst doctors that some other method was needed, be itarbitration or some special scheme for babies with cerebral palsy.For many health authorities, the burden of legal claims couldbecome too heavy and services could suffer. On the other hand,patients (and families) seriously injured as a result of negligence areentitled to compensation, which should be more readily availableand accessible. Sir Donald said that Medical Defence Union figuresshowed that the number of files opened in respect of claims forbrain-damaged babies had risen from 50 in 1982 to 150 in 1989. As aresult of a change in legal aid, enabling children to be assessedseparately from their parents, the figures for 1990 could be as high as600. Yet the proportion of babies likely to have been damaged as aresult of negligent obstetric care was very small. The panel ofspeakers was worried that decisions made by judges would notreflect the clinical truth of the situation. Judges can work only fromthe evidence before them, and this is likely to conflict in importantrespects. If both sides remained convinced of the rightness of theircases, the loser is bound to be dissatisfied with the system.The RCOG and the Government could do worse than

consider the proposals from the Royal College of PhysiciansWorking Party on Compensation for Medical Injuries,published last year. The Conservative Government, havingdismissed a private member’s compensation bill, did agreethat change was necessary, and a consultative document isthought to be in preparation. No-fault compensation is nowLabour Party policy. Relations between obstetricians andtheir patients could be improved now if obstetricians were tospeak more freely and frankly; some responsibility forpatient dissatisfaction, manifesting itself in negligence suits,must be laid at the doctors’ door. If medical, nursing, andother staff come over as unhelpful, evasive, and

unsupportive of a family into which a seriously handicappedbaby has been born, this is likely to suggest that there issomething to hide. The public need to be educated that aperfect outcome to pregnancy cannot be guaranteed.

Diana Brahams