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between transfusions (doses of antigen) given. ProfessorDiamond mentioned a group of 142 Rh-negative men,43% of whom had demonstrable antibodies ; 10% ofthese had had recorded reactions while another 33%had had symptoms and signs of reactions (not recordedas such) at the second, third, or subsequent transfusion.By contrast, immunity which has developed more slowly,as during a Rh-positive pregnancy in a Rh-negativemother, is stronger and more lasting and the subjectis more liable to reactions after transfusions of Rh-

positive blood, even the first. It is unwise to use a husbandas a donor for his wife if his Rh grouping is unknown-he might be Rh-positive and so sensitise or induce afatal reaction in his spouse. The importance of ante-partum, postpartum, or subsequent transfusions for

Rh-negative women being of blood compatible in ABOgroup and Rh-negative cannot be too strongly empha-sised. All women should be grouped (ABO and Rh)when first pregnant, and in affected and special casesthe simple and specific Rh (genotype) of the father andchildren should also be determined.

Infants who show gross hydrops at birth, or duringtheir first few days of life develop jaundice and anaemiawith erythroblastaemia, enlarged liver, and spleen,or with kernicterus and later muscle incoordinationand mental defect, are Rh-positive children of Rh-

negative mothers and Rh-positive fathers. Whenthe mother is Rh-negative and the father is Rh-positiveand homozygous (Rh-Rh) every foetus will be Rh-

positive and will develop haemolytic disease in some form.The chance of the foetus being affected will be reducedto 50% if the father is Rh-positive but heterozygous(Rh-rh)-thus, in heterozygous twin pregnancy the

healthy child is Rh-negative and the Rh-positive childis stillborn with hydrops or jaundiced. Since the firstchild of such unions, which constitute 13 % of all marriages,is usually unaffected, the general chance of a Rh-negativemother having an affected child is 1 in 22 and the over-allincidence of heamolytic disease is 1 in 200 births.

Until 1941 tests applied were unsatisfactory evenin proved cases of erythroblastosis fcetalis. In 1944Wiener and Race and Diamond were concerned withthe demonstration of "blocking" or incomplete- orhyperimmune-antibodies. With hyperimmune antiseraRh-testing is as simply done as tests for the ABO groups,and Professor Diamond emphasised that there is nowlittle excuse for the Rh, Hr, and Rh-Hr groups not beingdetermined as a routine. By using six different sera thegenotype can be determined with fair accuracy. Hyper-immune sera are prepared chiefly from Rh-negative malevolunteers by giving them at short intervals over a periodof several months 50 c.cm. transfusions followed by0-1 c.cm. injections of Rh-positive blood. By ordinaryagglutination methods, using red cells suspended insaline, the titre in these sera continues to rise for a timeand then falls sharply. The fall is explained by thepresence of " blocking " antibodies which are said tobe adsorbed to and to protect the red cells from agglu-tination in the test. When however the tests are repeatedwith the red cells suspended in plasma or albumininstead of saline, the high level of the hyperimmune or" blocking " antibody content is apparent and titresof 2000 or 4000 are recorded. Ordinary agglutinins aredemonstrable during the concerned pregnancies butare absent between and after them, while " blocking "antibodies may be demonstrated as long as 35 yearslater in a Rh-negative woman who has had a successionof children with hsemolytic disease. There is only theroughest correlation between the two titre levels andthe birth of children with haemolytic disease.

Jaundice and anaemia in the newborn remains a

clinical problem, though the mortality has been reducedby treatment based on the work of the last five years.Twenty years ago, when treatment was by intramuscular

injection of the father’s blood, 40% of cases succumbedto jaundice, cedema, or cardiac failure and 15% of thesurvivors showed evidence of brain damage. Between1941 and 1944 treatment was directed towards replacingthe destroyed red cells with Rh-negative blood in smalltransfusions and the case-mortality was reduced to 30%(Diamond). The fact that jaundice and anaemia appearedin such infants three to four days after birth suggestedthat earlier delivery (37th to 38th week, at the discretionof the obstetrician) might reduce the duration of actionof the maternal (haemolytic) antibody. Over a period oftwo years, in a series of 350 cases, Professor Diamondreduced the case-mortality to 20% by combining earlydelivery with small transfusions of Rh-negative blood.More recently it was shown that the cord blood oftenhas appreciable amounts of circulating Rh-antibody(carried over from the mother) and this suggestedtreatment by exsanguination-transfusion with Rh.negative blood as soon after birth as possible. Thetechnical difficulties of the method-clotting in cannulse,&c.-are considerable, said Professor Diamond, and sinceheparinisation is contra-indicated because of the tendencyof these children to bleed (hypoprothrombinsemia) heand his colleagues use a special plastic catheter passedinto the umbilical vein to reach the ductus venosus orinferior vena cava. The infant’s blood is graduallyreplaced with Rh-negative blood, 20 c.cm. at a timethrough a two-way syringe set-up, until after an hour500 c.cm. of blood has been transfused and 400 c.cm.of the infant’s blood replaced. The umbilical veinhas been used up to 18 hours after delivery; thereafterarm or leg veins are cut down upon and the plasticcatheter is passed into the subclavian or femoral vein.By this treatment the case-mortality has been reducedto 10%.Much work has yet to be done before all the tissue

changes and immunity mechanisms involved in this

group of diseases are fully understood.

CONSENT TO DEATH

THE Voluntary Euthanasia Society are planning toreintroduce into the House of Lords their Bill to legaliseeuthanasia for people suffering great pain from incurabledisease. The Bill, it will be remembered, was before theHouse in 1936 but was not given a second reading. At theannual meeting of the society, on May 21, Dr. E. A.Barton spoke of the risk taken by doctors who accedeto a patient’s appeal for release, and argued that a

responsibility of this kind should not rest on the shouldersof the doctor alone. In a contribution to the springissue of University College Hospital Magazine, he madethe same point at greater length. Though cases needingeuthanasia are rare-he has seen only half a dozen infifty years-they are peremptory : the impulse to helpthe patient at his own urgent plea is almost impossibleto deny. Many, he hopes, are willing " to risk criticismand worse by doing for a patient that which they woulddesire for themselves under similar circumstances."The present situation is sometimes cruel to the patient;

yet it is very doubtful whether legislation could makethings any better. The difficulties were discussed byDr. Harry Roberts 1 when the bill was last before theHouse. Were he himself dying of carcinoma of thethroat, he said, his hope would be that his doctor " with-out significant word or gesture " would " hasten the paceover a bit of bad going." He went on :

" My exit would not be quite such a happy one if, assuggested in the Voluntary Euthanasia Bill ... I had firsthad to make an application stating to the appropriateauthorities that I had been informed by two medical practi-tioners, whose certificates I enclosed, that I was sufferingfrom an incurable disease and that my nearest relatives

1. Euthanasia and Other Aspects of Life and Death, London,1936.

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had been notified ; my request being duly attested by amagistrate ; if, further, my application had then to besubmitted to an official ’ euthanasia referee,’ after whoseapproval seven days must elapse to allow time for appealby a relative to a court of summary jurisdiction, whichmay then cancel the permit. Only practitioners who hadbeen named for the purpose would be eligible to act aseuthanisers, and the administration must take place in thepresence of an official witness. I can almost hear thecheerful announcement : ’Please, ma’am, the euthaniser’scome.’ "

Dr. Barton, however, pictures no such cruel post-ponement of relief. He thinks England should be dividedinto areas, in each of which two doctors of high standingand ability would be registered, who would be calledin by the general practitioner to carry out the final act.The patient would have to ask relief, and only urgentpleas would be taken into account. The consent offriends would not be asked, for if it was refused the

patient must continue to suffer, whereas if it was given" misunderstandings might arise later." The two

specialists would see the patient together, without

anyone else in the room ; after which the patient’s owndoctor would be heard, and a clear decision made ; andafter that the patient would be released. This againwould mean moments of suspense and heavy responsibilityfor the patient.

THEIR FIRST CENTURY

AT their convention, which opens on June 9 in AtlanticCity, the American Medical Association will celebratethe 100th anniversary of their foundation ; and in his

history, which has been appearing as a pious serial inthe J.A.M.A. since last November, Dr. Morris Fishbeinaptly writes : "the birth of the Association followedtravail of many months ; the pains, the jealousies andthe love associated with its conception forecast the

great career to be achieved by this extraordinaryprogeny." Their first meeting was held at Philadelphiain 1847-the year in which Simpson first used chloro-form in obstetrics, Semmelweis discovered the cause

of puerperal fever, and Ludwig invented the kymograph.This year at the invitation of the association Prof. G. W.Pickering will give an address on Hypertensive Encephalo-pathy, Prof. H. J. Seddon on Nerve-grafting in the

Limbs, and Sir Howard Florey, F.R.S., on New Anti-biotic Agents. Other English guests will include Sir

Heneage Ogilvie, Dr. R. M. B. MacKenna, Prof. JohnMcMichael, Mr. G. E. Martin, Sir Stewart Duke-Elder,Dr. E. Ashworth Underwood, and Dr. A. R. Hunter.A commemorative 3-cent maroon postage-stamp is tobe issued by the United States government, and thedesign chosen is Sir Luke Fildes’s picture The Doctor.

INTESTINAL ANTHELMINTICS

A RECENT recommendation 1 in France to place oil ofchenopodium and its active principle ascaridole intable C of their poisons list directs attention to the possibledangers of anthelmintics or vermifuges. Ascaridolehas undoubtedly been responsible for occasional fatalities,but it is well to recall that none of the intestinal anthel-mintics is free from such a risk. In the mass treatmentof tropical populations for worm infestation deaths haveresulted from the use of almost every known anthelmintic.

In normal clinical practice the chance of accidents inthe treatment of intestinal parasites can be minimised byfollowing a few principles. Individual idiosyncrasy to anyof the usual anthelmintics is almost impossible to fore-cast, but happily rare. Some protection against it canbe obtained by giving the full dose of the drug in threeparts at half-hour intervals, rather than as a singledraught ; if the first dose produces ill effects the otherscan be abandoned. Dividing the dosage is also to becommended because it prolongs the contact of the drug

1. Fabre, R. Bull. Acad. nat. Méd. 1946. 131, 226.

with the worms and thus increases its action. Mostintestinal anthelmintics are soluble in alcohols and inabsorbable oils and fats. These solvents must thereforebe avoided over the period of treatment, to lessen therisk of the drugs being absorbed from the gut. Again,once the drug has done its work it should be removedfrom the body as completely and as rapidly as possible,further to lessen the risk of absorption. To this end avigorous saline purge should be given one or two hoursafter the last dose of the drug, to sweep it from thebowel. This vigorous purgation serves the added

purpose of removing worms temporarily incapacitatedby the drug, which if left in the bowel would recoverand re-establish themselves there. If these simpleprecautions are taken anthelmintic treatment can beembarked on in otherwise healthy patients withoutanxiety and with a good hope of success.

SMALLPOX IN NEW YORK

SMALLPOX is a rare cause of death these days in theUnited States. In the last fifteen years fatal caseshave never exceeded 50 annually, though Seattle had68 cases, with 20 deaths, last year. It is thirty-fiveyears since anyone died of the disease in Manhattan,but this record has now been broken by the death of aMexican businessman who had travelled from Mexico

City to New York a week before by bus, a four days’journey. The Mexican felt ill on arrival. His wifetook care of him at their hotel for a time but finallysent him to hospital, where he died. His symptoms wereatypical, and nobody knew he had had smallpox untiltwo people at the hospital developed a typical eruption.Immediately the public-health services were mobilised.The city of New York set out to vaccinate its 7,500,000inhabitants in three weeks. Air transport solved theproblem of getting enough vaccine, and the programmewent ahead at the rate of 250,000 a day. Dispensaries,hospitals, police stations, factories and offices, labourunion halls, and doctors’ surgeries were transformedinto clinics, and the newspapers and radio stationsdistributed official announcements and advice to the

public. Meanwhile the route of the bus was traced and

precautions were set on foot along the way. In Camden,New Jersey, there was a death from smallpox, and massvaccination began immediately there and in Philadelphianearby. Jersey City, across the Hudson from NewYork, immunised 50,000 inhabitants, and the State ofNew Jersey authorised the expenditure of$65,000 toimmunise 180,000 people. The Americans have not

forgotten the tragic example of Manila, in the Philippines,where vaccination had become lax and a sudden epidemicin 1914 caused 50,000 deaths. In England mass vaccina-tion during an outbreak is not ordinarily adopted. As.Dr. W. H. Bradley told the Royal Sanitary Institute onMay 14, last year 15 introductions of the disease fromoutside led to only 40 secondary cases, thanks to theprompt application of routine measures of control.

THE NEW REGIONAL POSTS

NAMES of members of the 14 regional hospital boardsappointed by the Minister of Health under the NationalHealth Service Act will probably be announced in thenear future. Each board will require an administrativemedical officer, and doubtless one of its first acts will b&to advertise this important post. The salary offeredis likely to range from E2000 a year in the two smallestregions to f2500 in the largest ones, and the appoint-ments made will be of interest not only to the successfulcandidates but also to the whole profession.

WE regret to announce the death on June 1 of Dr.N OAR MoRRIS, regius professor of materia medica andtherapeutics in the University of Glasgow ; and on June 3of Dr. RICHARD CLITHEROW, M.P.