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particular reference to a slowly progressive variety. Brain 1964; 87:707-19.

5. Wohlfart G, Fex J, Eliasson S. Hereditary proximal spinal muscularatrophy-a clinical entity simulating progressive muscular dystrophy.Acta Psychiatrica Neurol 1955; 30: 395-406.

6. Kugelberg E, Welander L. Heredofamilial juvenile muscular atrophysimulating muscular dystrophy. Arch Neurol Psychiatry 1956; 75:500-09.

7. Emery AEH. The nosology of the spinal muscular atrophies. J Med Genet1971; 8: 481-95.

8. Hausmanowa-Petrusewicz I, Zaremba J, Borkowska JJ. Chronic

proximal muscular atrophy of childhood and adolescence: problem ofclassification and genetic counselling. J Med Genet 1985; 22: 350-53.

9. Emery AEH, Davie AM, Holloway S, Skinner R. Internationalcollaborative study of the spinal muscular atrophies. J Neurol Sci 1976;30: 375-84.

10. Melki J, Abdelhak S, Sheth P, et al. Gene for chronic proximal spinalmuscular atrophies maps to chromosome 5q. Nature 1990; 344:767-68.

11. Brzustowicz LM, Lehner T, Castilla LH, et al. Genetic mapping ofchronic childhood-onset spinal muscular atrophy to chromosome5q11·2-13·3. Nature 1990; 344: 540-41.

12. Southern EM. Detection of specific sequences among DNA fragmentsseparated by gel electrophoresis. J Mol Biol 1975; 98: 503-17.

13. Leppert M, Wasmuth J, Overhauser J, et al. A primary genetic linkagemap to chromosome 5. Cytogenet Cell Genet 1987; 46: 649.

14. Lathrop GM, Lalouel JM, Julier C, Ott J. Strategies for multilocuslinkage analysis in humans. Proc Natl Acad Sci USA 1984; 81:3443-46.

15. Morton NE. The detection and estimation of linkage between the genesfor elliptocytosis and the Rh blood type. Am J Hum Genet 1956; 8:80-96.

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19. Lyonnet S, Caillaud C, Rey F, et al. Guthrie cards for detection of pointmutations in phenylketonuria. Lancet 1988; ii: 507.

Preliminary report: hepatic vein doppler in the earlydiagnosis of acute liver transplant rejection

37 transplanted livers (in thirty patients) wereassessed by serial doppler ultrasound examination.18 of 23 biopsy-proved rejection episodes wereassociated with abrupt damping of the normallypulsatile blood flow of the hepatic veins. In theother 5 episodes, the waveforms were damped atthe outset by perioperative ischaemia. There wereno rejection episodes with normal traces. Anothercause of damping was cholangitis (5 episodes), butthis was distinguishable clinically and

biochemically. There were no episodes of rejectionwith normal hepatic vein traces. Serial dopplerexamination, in combination with clinicalevaluation, may allow earlier diagnosis andtreatment of liver rejection.

Introduction

The commonest cause of early graft dysfunction after livertransplantation is acute rejection1 and many imagingmethods have been advocated for its diagnosis.2 ’ Since onlysevere rejection is reliably detected, they are of limited valueand liver biopsy remains essential. Doppler ultrasound maybe helpful in showing hepatic artery or portal vein

occlusion,5,6 but as yet has no place in the diagnosis ofrejection.’ In the normal liver, doppler of the hepatic veinsreveals a pulsatile velocity profile that mirrors the cyclicalchanges in right atrial pressure. During the cardiac cyclethere are periods of retrograde flow in the hepatic veinscorresponding to the a and v wave components of the venouspulse8,9 (fig 1). In chronic liver disease this waveform may beseverely damped,10 but there are no published data on theappearances in acute liver disease or soon after

transplantation. We report our experiences of hepatic vein

doppler examination after liver transplantation, in childrenand young adults, over eighteen months.

Subjects and methodsBecause our ultrasound resources are limited, we decided to includeonly those patients passing through the paediatric unit (aboutone-third of the total number of transplants done). 37 consecutiveliver transplants in thirty patients (aged 1-20 yr) were studied forthree weeks after transplantation. In most cases a complete child’sliver was transplanted, but in six a cut-down left lobe from an adultdonor was used." Hepatic function was assessed daily bymeasurement of serum bilirubin, alkaline phosphatase,. andaspartate aminotransferase and clotting times (prothrombin andpartial thromboplastin times). In all cases of unexplaineddeterioration in hepatic function or clinically suspected rejection,biopsy specimens were taken before treatment. Routine ultrasoundexamination of the liver and doppler examination of the hepaticvessels were performed within 24 h of operation and every 2-3 daysthereafter. Additional scans were done if clinically indicated and atthe time of biopsy.

Examinations were made by one of three experienced operatorsusing an Aloka 650 SSD machine with a 3-5 or 5 MHz curvilinearprobe. No special patient preparation was required. The scans weredone with the patient supine and breathing quietly (or, in the earlypostoperative period, during mechanical ventilation). Pulsed

doppler recordings were obtained from the hepatic artery, portalvein, and the three main hepatic veins. For the hepatic veins, a10 mm sample volume was used, about 4-6 cm proximal to theinferior vena cava. The large sample volume ensured that part of the

ADDRESSES: Departments of Radiology (R. A. Coulden, FRCR,P D. Britton, FRCR, F Farman, DCR),Paediatrics (G. Noble-Jamieson, MRCP), and Pathology (D. G. D. Wright, FRCPath),Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. Corres-

pondence to Dr R. A. Coulden, Department of Cardiology, ManchesterRoyal Infirmary, Manchester M13 9WL, UK.

274

Fig 1-Doppler ultrasound of hepatic vein showing normalvelocity profile in a healthy volunteer.

The sample volume lies on the line within the right hepatic vein Dunngright atrial contraction (a wave) blood refluxes into the liver This appearsas a doppler signal above the dotted line.

insonated vessel remained within the "gate" throughoutrespiration.

Results

After an uncomplicated transplant, the pulsatility profile inthe hepatic veins was normal. In 37 liver transplants therewere 23 biopsy-proved acute rejection episodes; 18 of thesewere associated with abrupt damping of the hepatic veinwaveform, recorded before the result of biopsy was known(fig 2); in 8 instances pulsatility changes preceded thedevelopment of clinical or biochemical evidence of rejectionby 24 h (by 36 h in 2 of these). In the remaining 5 episodes ofrejection perioperative ischaemia was present and thewaveforms were severely damped at the first examination.There were no episodes of biopsy-proved rejection withnormal hepatic vein traces. No difference was noted in theease of diagnosis between whole-liver and left-lobe grafts.

Regular ultrasound scanning provided additionalinformation. 23 intra-abdominal fluid collections and 4acute vascular occlusions were demonstrated (table). Noneof the fluid collections produced a change in hepatic veinwaveform. The vascular occlusions were already suspectedon clinical or biochemical grounds and the diagnosis was

ADDITIONAL INTRA-ABDOMINAL FINDINGS DURING ROUTINE

SCANNING

validated by doppler. On three occasions focal areas ofhepatic infarction without doppler evidence of large vesselocclusion were identified. Each of these was associated witha large rise in serum hepatic enzymes. The ultrasound/doppler findings were confirmed by laparotomy in two andby biopsy in one. There were five episodes of cholangitis. Allthese patients had damped hepatic vein waveforms butpyrexia and positive bile cultures distinguished them fromthose with acute rejection.

Discussion

The pulsatility of the hepatic vein trace probably reflects themacroscopic compliance of liver tissue. Pathologicalprocesses that change compliance will lower hepatic veinpulsatility. In the first weeks after transplantation, thecommonest causes of graft dysfunction are perioperativeischaemia, vascular catastrophe, acute rejection, cholangitis,and functional cholestasis.1 In our experience, perioperativeischaemia, rejection, and cholangitis may all cause dampingof the doppler trace. Perioperative ischaemia, when present,is always seen on the first postoperative examination andfrequently recovers with a corresponding increase in hepaticvein pulsatility. Cholangitis may be distinguished fromrejection on clinical and microbiological grounds. Thereforean abrupt loss of pulsatility without evidence of cholangitiscan be acute rejection. On the evidence of this series, thepositive predictive value of this finding was 78% (taken toindicate true positive test result/true positive + falsepositive). There were no episodes of rejection with normalhepatic vein pulsatility, thus negative predictive value was100% (true negative test result/true negative + falsenegative). Since functional cholestasis was not associatedwith a change in waveform, a clear distinction could be made

Fig 2-Doppler traces of right hepatic vein in a 15-year-old post transplantation.

A normal pulsatile trace with a wave reflux is seen on day 1 On day 8 there is abrupt damping of the waveform and liver biopsy confirmed acute rejection.On day 11, after 3 days of antirejection therapy, normal pulsatility is restored (right)

275

between functional cholestasis and rejection, eliminating theneed for liver biopsy in these cases. Where rejection hasbeen diagnosed on doppler criteria (cholangitis excluded),there is an argument for instituting anti-rejection therapywithout biopsy and its inherent risks.The number of intra-abdominal fluid collections

discovered by routine scanning is consistent with results ofother studies.12 Although many were perihepatic, there wasno evidence that these had any effect on hepatic veinwaveform. The 4 cases of acute vascular occlusion were allfound by doppler and were confirmed by laparotomy ornecropsy. The effect on hepatic vein pulsatility varied. Focalinfarction did not alter the underlying doppler trace.Our most important fmding was that the changes in

hepatic vein waveform, and hence liver compliance, mayprecede clinical and biochemical evidence of rejection by upto 36 h. The protocol for this pilot study provided forexaminations every 2-3 days and early diagnosis may havebeen due to the chance timing of the doppler investigationrelative to the rejection episode. If doppler examinationwere done every day, the proportion of rejection episodesdetected 24-36 h early might exceed the 39% (7/18) seenhere. The response to antirejection therapy in acute episodesis related to the severity of rejection at the time of diagnosis. 13We hope that earlier diagnosis with hepatic vein doppler andprompt treatment will improve graft function and survival.Although this work is based on children and young adults,our experience suggests that the observations are valid inolder patients.

The patients were under the care of the surgeons of the department of surgery(head, Prof R. Y. Caine), whom we thank.

REFERENCES

1. Demetris AJ, Lasky S, Van-thiel DH, Starzl TE, Dekker A. Pathology ofhepatic transplantation. Am J Pathol 1985; 118: 151-61.

2. White RM, Zajko AB, Demetris AJ, Bron KM, Dekker A, Starzl TE.Liver transplant rejection: angiographic findings in 35 patients. Am JRoentgenol 1987; 148: 1095-98.

3. Dominguez R, Cuervas-Mons V, Van-Thiel DH, Lecky J, Starzl TE.Radiographic features of liver allograft rejection. Gastrointest Radiol1986; 11: 326-29.

4. Wechsler RJ, Munoz SJ, Needkemnan L, et al. The periportal collar: aCT sign of liver transplant rejection. Radiology 1987; 165: 67-60.

5. Taylor KJW, Morse SS, Weltin GG, Riely CA, Flye MW. Livertransplant recipients: portable duplex ultrasound with correlativeangiography. Radiology 1986; 159: 357-63.

6. Flint EW, Sumkin JH, Zajko AB, Bowen A. Duplex sonography ofhepatic artery thrombosis after liver transplantation. Am J Roentgenol1988; 151: 481-83.

7. Longley GD, Skolnick ML, Sheahan DG. Acute allograft rejection inliver transplant recipients: lack of correlation with loss of hepatic arterydiastolic flow. Radiology 1988; 169: 417-20.

8. Appleton CP, Hattle LK, Popp RL. Superior vena cava and hepatic veinDoppler echocardiography in healthy adults. J Am Coll Cardiol 1987;10: 1032-39.

9. Coulden RA, Britton PD. Hepatic vein Doppler: a new pulsatility indexand normal ranges for different physiological parameters. In:

Proceedings of Royal College of Radiologists Annual Scientific

Meeting, Liverpool, September 1989 (abstr).10. Rees JI S, Whyte A, Cochlin DL. Doppler ultrasound in the investigation

of hepatic parenchymal disease. In: Proceedings of 21st meeting ofBritish Medical Ultrasound Society, Torquay, December 1989 (abstr).

11. Bismuth H, Housin D. Partial resection of liver grafts for orthotopic orheterotopic liver transplantation. Transplant Proc 1985; 17: 279-83.

12. Raby N, Meire HB, Forbes A, Williams R. The role of ultrasoundscanning in management after liver transplantation. Clin Radiol 1988;39: 507-10.

13. Snover DC. The pathology of acute rejection. Transplant Proc 1986; 18:123-27.

BOOKSHELF

Educating Competent and Humane PhysiciansEdited by Hugh C. Hendrie and Camille Lloyd. Bloomington,Indianapolis: Indiana University Press. 1990. Pp 223.$29.95.ISBN 0-253327253.

Much of the current literature on the sad state of medicaleducation seems to have little relevance to the kind of youngpeople that I meet on my wards. Certainly today’s studentsand young doctors are more aware of the humane and

pastoral aspects of clinical practice than my generation orthat which taught me. I can still vividly recall my first wardround. We arrived at the bedside of a patient who had justbeen diagnosed as having cancer. The consultant steered hisentourage away from the bed, organised an Americanfootball huddle in the middle of the ward, and, soto voce,discussed the prognosis. We then returned to the patient,banalities were shared, no explanation was given, and on wemoved. Today’s students would never tolerate thisbehaviour. Yet, despite genuine improvements in attitudesto patient care, medical education is the subject of everincreasing soul-searching.The concerns are always the same: the cadaver in whose

company students spend their early years is not the idealcompanion with which to launch them on careers as

sympathetic communicators; the course is overcrowded;teaching is too hospital based; the basis sciences are over (orunder) emphasised; legal matters, ethics, and even businessmanagement are neglected; and so on. The frustrating partof these discussions is that there is no way of evaluating theend product and hence of comparing one approach tomedical education with another. In the UK great store is puton final qualifying examinations and postgraduatediplomas. But although these rituals undoubtedly test theacquisition of the knowledge and techniques required of acompetent clinican they are incapable of assessing whether acandidate will be a good doctor.

In Educating Competent and Humane Physicians theeditors and a team of fellow psychiatrists, all but one fromthe USA, offer their ideas on how to educate more humanephysicians. Their theme is that advances in psychosocial andneurobiological sciences have moved at such a pace thatfamiliarity with the "harder" biological sciences, as

currently taught, is not sufficient by itself for the practice ofmedicine. In other words, because they believe that it is nowpossible to teach and assess communication, empathy, andan understanding of psychosomatic factors as the basis ofdisease, more time should be devoted to these topics.

Although the authors do not provide any completely newapproaches to these important aspects of medical education,or how to measure the end result, the book is well worthreading by those interested in medical students because, inbetween some irritating jargon, it offers good common-sense advice about training clinicians, and in particular,about making students feel welcome and appreciated in theinstitutions in which they are being taught. Its mainweakness is that it tackles only one aspect of medicaltraining. In particular it does not face the problem of how tobridge the gap between the increasing reductionism ofhuman biology and the humane and holistic skills requiredof a physician-surely one of the most challenging questionsfor medical educators. How do we combine developing theattitudes which Hendrie and Lloyd rightly demand of