715

of the coronary arteries and the circumflex artery was not dis-

played. The coronary studies 16 months after portacaval shuntrevealed all three coronary arteries, of which none had diffusenarrowing. The general internal dimensions of the coronaryarteries would now be considered normal except for threediscrete areas of occlusive disease--one at the bifurcation of theleft coronary artery into the circumflex and left anterior descend-ing arteries, one more distal in the circumflex artery, and one inthe right coronary artery.The residual myocardial insult from the previous infarction

has been serious. Left ventricular end-diastolic pressure is34 mm Hg, and myocardial contractility and cardiac outputare compromised.

Atherosclerosis can be induced in laboratory animals byfeeding a high-cholesterol diet with or without other

experimental manoeuvres such as total thyroidectomy. Theresulting vascular lesions have been shown to be reversibleif the causal factor(s) is removed.4-6 However, there havebeen no unequivocal examples of such a reversal of cardio-vascular disease in man. This was shown to have occurredin our patient, in whom there were anatomical and hsemo-dynamic changes at the aortic valve. Anatomical changesin the coronary arteries were more difficult to assess, butpresumably the transition from diffuse narrowing to

highly localised stenosis represents improvement. Althoughmyocardial infarction had already occurred before the

portal diversion, producing severe and persistent myo-cardial impairment, protection of the remaining myo-cardium by improving its blood-supply and reducing itswork should be beneficial.The reason for cholesterol-lowering by portal diversion

is still uncertain. It was previously speculated that theeffect was due mainly to the bypassing around the liver ofendogenous hormones derived from upper splanchnicorgans.l Of these hormones, insulin was assumed to playa dominant role. The hormone hypothesis has been

strengthened by experiments (unpublished) in normal

dogs and baboons in which mesenteric venous to venacaval shunts were performed. This bypass of nutrient-richintestinal blood did not affect the serum-lipid concentra-tions. At a second stage, the portal vein in the liver hilumwas detached and anastomosed to the vena cava; the

consequent diversion of the hormone-rich venous effluentfrom the upper splanchnic organs depressed the serum-cholesterol. Portal diversion seems to reduce cholesterolor lipoprotein synthesis in such studies, but changes incholesterol and lipoprotein degradation have not beenruled out as a contributory factor. Without a better

understanding of the mechanism of the benefit from portaldiversion, it would seem superfluous to comment on theelevation of cholesterol levels during the two episodes ofpneumonia and congestive heart-failure beyond notingthat these increases may have been related to the adminis-tration of chlorothiazide. Frusemide did not cause a

similar rise.We are aware of a second patient with homozygous

type-n hyperlipoproteinaemia who has also experiencedlowering of serum-cholesterol levels following portacavalshunt, and it is likely that other patients will undergo thisoperation in the near future. The suggestions for detailedpreoperative and postoperative evaluations, and the

development of a registry 7 of all patients being con-

sidered for or having received the operation, seem important.Our present belief is that homozygous type-li patientswho show evidence of cardiovascular disease and whohave not adequately responded to lipid-lowering medica-

4. Anitschkow, N. in Arteriosclerosis (edited by E. V. Cowdrey);p. 271. New York, 1933.

5. Bevans, M., Davidson, J. D., Kendall, F. E. Archs Path. 1951,51, 288.

6. Armstrong, M. L., Warner, E. D., Conner, W. E. Circ. Res. 1970,27, 59.

7. Ahrens, E. H., Jr. Lancet, Aug. 24, 1974, p. 449.

tion should be considered for the portacaval shunt, hope-fully prior to myocardial infarction.

This work was supported by research grants from the VeteransAdministration; by grants AI-AM-08898, AM-07772, andHL-05981 of the National Institutes of Health; and by grantsRR-0051 and RR-00069 from the General Clinical ResearchCenters Program of the Division of Research Resources, NationalInstitutes of Health.

Departments of Surgery andPediatrics,

University of ColoradoMedical Center and

Veterans Administration Hospital,Denver, Colorado 80220, U.S.A.

THOMAS E. STARZLH. PETER CHASECHARLES W. PUTNAM

JAMES J. NORA.

LEGAL STATUS OF THE UNBORN

IR,—Medical Knowleage 01 tne causes and preventionof congenital defects is expanding rapidly. A number ofteratogenic agents have now been identified and, withadvances in medical genetics, it is now known which

genetic disorders are likely to recur in a family. In manyof these genetic disorders antenatal diagnosis with selectiveabortion of affected fetuses is possible.1 Thus, the meansexist to prevent many congenital malformations andgenetic disorders. But this is possible only when theproblem is recognised, and in the case of genetic disordersthe parents are given genetic counselling and subsequentlyrespond to this advice either by effective contraception orby accepting antenatal diagnosis with selective abortion.A number of legal problems follow from these develop-ments and therefore the report by the Law Commissionis welcome.The Commission’s remit was to advise what the

nature and extent of civil liability for antenatal injuryshould be ". The Commission took evidence from bothmedical and legal experts in formulating their report, themain conclusions of which are of particular interest toclinicians concerned with antenatal care in its broadestsense.

There is a feeling in several parts of the world, par-ticularly in the United States, that the fetus might beinvested with legal status. This might mean that it couldbring an action for " wrongful life " if parents did not

agree to termination if the fetus were known to be affected.In this way it could be argued that the child would havebeen better off had he never existed. The illogicality ofthis was recognised by the Commission, who have thereforeadvised that the fetus should not be invested with rightsand that there should be no liability for " wrongful life ".One particular danger of accepting such a liability wouldbe that doctors might be under subconscious pressures toadvise abortion in doubtful cases through fear of an actionfor damages. The Commission also felt that, apart fromfetal injuries resulting from negligent driving of a motorvehicle, a child born alive should not have a right of actionagainst the mother accruing in respect of any " act oromission during or before pregnancy " which causes

injury to the fetus. The contrary view ought to yield tosocial acceptability and natural sentiment. But the Com-mission seems primarily to have been concerned with

physical injury rather than with possible harmful geneticeffects. If parents have been informed through geneticcounselling that they are at risk of having a child with aserious genetic disorder, and have also been made aware ofthe possibility of antenatal diagnosis, could they defendtheir action in law if knowingly they subsequently had anaffected child ? We have so far considered that this is theprerogative of parents in a free society, but will this be so

1. Lancet, Aug. 31, 1974, p. 503.2. Report of the Law Commission no. 60. H.M. Stationery Office,

London. 1974. 50p.

716

in the future ? For religious or other reasons some parentsmight well reject the idea of contraception or antenataldiagnosis with selective abortion.A further problem arises from the introduction of

techniques for antenatal diagnosis. These techniques arecomplex and require considerable expertise. If a mistakeis made and a child with a serious deformity is born, arethose individuals who carried out the tests likely to be thesubject of litigation ? The Commission’s report is nothelpful on this point, but whether or not the defence of" acting in good faith " would be acceptable is a moot

point. In the very near future the profession will requireexpert legal guidance in these matters.Department of Human Genetics,

Western General Hospital,Edinburgh EH4 2HU. A. E. H. EMERY.

DISPENSING DOCTORS

SIR,-I was surprised that David McKie (Sept. 7, p. 583),in his article on the disappearing chemist’s shop, did notpoint out the possible virtues of encouraging more doctorsto dispense. To do so would require a new flexibility in therule preventing doctors dispensing to patients living withina mile of the nearest chemist. But, apart from the fact thatdoctors are, quite fairly, paid less than chemists for dispens-ing, and so provide a cheaper service for the N.H.S., theadvantages to a patient of receiving drugs from the doctorat the time of prescribing are very real.

In ten years in a part-dispensing semirural practice, I

provided rural patients with drugs not only in the surgery,but also in their homes, by carrying a portable, limited,but adequately comprehensive range of drugs in a speciallydesigned box in the back of my car. I used to feel sorry forthose patients who were denied this service by the exist-ence of the one-mile rule.

Cobbetts, Town Row,Rotherfield, Sussex. J. M. HUGHES.

RAPID CHROMOSOME DIAGNOSIS

SIR,-Dr Smithies and Dr Valman reported that acytogenetic diagnosis could be made from bone-marrowcells five hours after the sample had been aspirated. Thiswas an improvement over an eight-hour diagnostic pro-cedure mentioned by Shaw.2 We have found that this timecan be shortened to two hours.

An infant girl was born at 32 weeks’ gestation in severe respira-tory distress. The following malformations suggested a clinicaldiagnosis of 18-trisomy syndrome: microphthalmia, low-setmalformed ears, webbed neck, overlapping of index fingers,and rocker-bottom feet. Small dermal patterns (arches and loops)were present on the fingers. When the question of managementarose, rapid confirmation of the clinical diagnosis became urgent.A sample of bone-marrow was aspirated from the iliac crest andwithin two hours the presence of an extra chromosome no. 18was confirmed in 7 cells. No extraordinary measures were takento prolong life and the infant died a few hours later. Furtherconfirmation was provided by fluorescent banding of lymphocytechromosomes prepared from peripheral blood cultures.

Similar rapid karyotyping was performed on a sample of fluidobtained before necropsy from the chest of a stillborn girl witha differential diagnosis of 13-trisomy syndrome or Potter’ssyndrome. The malformations suggestive of 13 trisomy werecleft lip and palate and polydactyly of both hands. An apparentlynormal karyotype was quickly demonstrated. Necropsy con-firmed a diagnosis of Potter’s syndrome. Subsequent chromo-some-banding analysis on a sample of cord blood identified apericentric inversion of chromosome no. 9 transmitted by thefather.

1. Smithies, A., Valman, H. B. Lancet, 1974, i, 1056.2. Shaw, A. New Engl. J. Med. 1973, 289, 885.

Method.-l ml. of bone-marrow aspirate was placed in 4 mlof culture medium containing 0-4 ml. of heparin. In the labora-

tory this specimen was divided into two centrifuge tubes and madeup to 10 ml. each with medium enriched with 20% fetal calfserum. 0-2 ml. of colcemid was added to each tube and left tosit at room temperature for one hour. They were then centri-fuged at 800 r.p.m. for 5 minutes, the supernatant was discarded,and the cells were washed with phosphate buffer solution.Hypotonic treatment and fixation followed in the usual fashicn.The fixed cells were chilled in the freezer for 15 minutes beforeair-dried slides were prepared. The slides were stained with a

drop of 2% acetic orcein (toluidene-blue if chromosome bandingis to follow), a coverslip was added, and the chromosomeswere analysed immediately.Some complaints have been voiced by physicians that

karyotyping has limited use because of the length of timetaken to obtain results. In urgent cases a diagnosis can bemade on cultured lymphocytes in three days (withoutchromosome-banding studies) while karyotyping of bone-marrow cells can be performed within two hours. Thissimple and rapid technique can be of considerable valueto physicians and parents faced with the question of manage-ment.

Regional Cytogenetics Laboratory andDepartment of Pediatrics,McMaster University,Hamilton, Ontario.

C. P. VIOLA LEEA. B. MACMILLANIRENE A. UCHIDAC. Y. YEUNG.

REYE’S SYNDROME

SIR,-Dr Thaler and his colleagues (Aug. 24, p. 438)described defective ornithine transcarbamylase (o.T.c.)in the liver of a child with Reye’s syndrome: activity was20% of normal and Km (for ornithine) was increased18-fold. The authors did not measure carbamyl-phosphatesynthetase (c.p.s.).We reported the activity (though not the Km) of o.T.c. and

c.p.s. in hepatic specimens of two patients with Reye’ssyndrome 1; we have since extended these measurementsto two additional patients with similar results. They arepresented here for their possible bearing on Dr Thaler’s

ACTIVITY OF CARBAMYL-PHOSPHATE SYNTHETASE (C.P.S.) AND

ORNITHINE TRANSCARBAMYLASE (O.T.C.) IN NORMAL HUMAN

LIVER AND LIVER OF FOUR PATIENTS WITH REYE’S SYNDROME

* Mean t 1 s.D. t Biopsy.

therapeutic suggestions. One specimen was obtained bybiopsy, the other three at necropsy. The results (obtainedby published methods 2 and expressed in nanomolescitrulline formed per mg. liver protein per minute) werecompared with " control " values in two biopsy and elevennecropsy specimens; whether they were obtained by biopsyor necropsy did not seem to affect the values.Mean activity of o.T.c. and c.p.s. in Reye’s syndrome

was reduced to 37% and 57% of normal (P<0-005 and0-01, respectively, using the t test for comparison of means).

1. Brown, T., Brown, H., Lansky, L., Hug, G. New Engl. J. Med.(in the press).

2. Brown, H. in Hepatic Failure (edited by I. N. Kugelmass); p. 63.Springfield, Illinois, 1970.