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individual variations in the absorptive capacity of thegut." Stewart and his colleagues have now producedevidence supporting their previous contention. Whenthe radioactive penicillin was given to cats by mouth,the urinary excretion of radioactivity was no longercomplete as when the penicillin was given intra-
muscularly, but was reduced to 54-24% of the initialdose, while the proportion of biologically active penicillinexcreted in the urine was even considerably less than this.In one cat only 24% of the original radioactivit3 hadappeared in the urine, and as much as 59% wasunabsorbed, being recoverable from the gut contents
post mortem. In this case urinary excretion had notended, but the presence of such a large percentage of theoriginal activity in the gut after six hours stronglysuggests that non-absorption from the gut is the reasonfor the low urinary excretions after oral penicillin.It seems, then, that attempts to improve the absorptionby this route are still worth while.
MEMORANDUM ON RH FACTORS
THE doctor who studies recent reviews and pronounce-ments on the Rh factor may well despair of ever under-standing this example of what Lord Samuel calls"the unceasing elaboration of human knowledge " ;the rows of rival symbols, the genetic terminology, the"
blocking " antibodies, all combine to bewilder him.Yet for the sake of his patients he must understandthe practical application of this new knowledge. Hewill be greatly helped by the brief, informative, andinexpensive summary published this week by theMedical Research Council,1 Without shirking descriptionsof the more difficult points, this memorandum presentsa clear picture of the clinical consequences of neglectingthe Rh factors, and it puts subjects like the Rh sub-groups and the peculiarities of Rh antibodies into theirproper perspective.
After a very short historical introduction, the first
section, by R. R. Race, describes briefly .the variousRh groups. He points out that 95% of all dangers
. due to Rh blood-groups are due to the original Rh groupnow known as D and its antibody anti-D, and he quotesthe latest figures showing that in England 83-2% of thepopulation are Rh-positive (D-positive) and 16-8%Rh-negative. There follows a brief but thoroughdescription of the Rh subgroups and their geneticrelationship according to the ideas of R. A. Fisher.Race rightly says that anyone who makes the effort
necessary to master these groups has, at the same time,achieved at least an elementary knowledge of human
genetics in general. In describing the Rh antibodiesthe term " blocking " antibodies is dropped, since it isnot clear that this is, in fact, the action of these anti-bodies. What is known is that anti-D, the commonestRh antibody, exists in two forms ; one form will
agglutinate red cells containing the antigen D (D-positivecells) when these cells are suspended in saline solution,whereas the other will agglutinate them only if they .are suspended in a protein medium-best results are
obtained with 20% bovine albumin. Cells exposedfirst to this albumin anti-D will not subsequently beagglutinated by the saline antibody ; hence the term" blocking " or incomplete antibody. But when Diamondgave intravenous injections of Rh-positive blood to
Rh-negative male volunteers, he found that the salineagglutinins appeared first, and that then with repeateddoses they diminished and eventually completely dis-
appeared, being replaced by a rising titre of the anti-bodies detectable only in albumin suspension. Diamondtherefore regards the albumin antibodies as " hyper-immune agglutinins." The authors of the M.R.C.
1. The Rh Blood Groups and their Clinical Effects. By P. L.Mollison, A. E. Mourant, R. R. Rate. M.R.C. Memo. no. 19.H.M. Stationery Office. 1948. Pp. 74. 1s. 6d.
memorandum adopt the noncommittal but descrip-tive terms " saline " and " albumin " agglutinins or
antibodies.In the second section P. L. Mollison deals with clinical
considerations and covers more familiar ground. Hedetails how immunisation to Rh can be produced bytransfusion of Rh-positive blood into Rh-negativepersons or by a pregnant Rh-negative woman having aRh-positive foetus. A less well-known fact is that theintramuscular injection of blood-e.g., for eczema-
can produce life-long immunisation. Mollison emphasisesthe importance of detecting Rh antibodies in the mother’sblood, since this is the best indication that -the infantmay be affected by haemolytic disease. Two examina-tions should be made, one early in pregnancy and oneabout six weeks before the expected date of delivery;the first examination reveals sensitisation producedbefore pregnancy, since antibody developing for thefirst time during a pregnancy rarely shows before thefifth month. The clinical pictures of haemolytic diseaseand of the allied syndromes are described, and the variousmeans of dealing with the situation and the question ofadvising parents about future pregnancies are fullydiscussed. The technical details of exchange trans-fusion provide useful practical points for workers inmaternity hospitals.
Clinical laboratories are not at present encouragedto undertake Rh testing, and the regional transfusionlaboratories do, most of this work. However, someclinical pathologists may be interested in doing theirown, especially if they are in situations distant from theregional centres. They will obtain comprehensivehelp from the third section, in which A. E. Mourantfully sets out the practical details of Rh testing.Altogether this is a highly valuable and authoritativeaddition to the M.R.C. series of White Memoranda.
THE ARTIFICIAL HEART
ATTEMPTS have been made since the turn of the
century to devise a machine which would perform thecirculatory duties of the heart. Twenty years ago Daleand Schuster showed that this could be done, and theperfusion pump that they devised and demonstratedat University College, London, is still in use. Butwhen, in addition, physiologists sought to oxygenatethe blood mechanically outside the body, the task becamemuch more complicated. So far the only fully efficientoxygenator has been the isolated lungs. Some of theearlier attempts at artificial oxygenation now seem rathercrude ; hydrogen peroxide and oxygen have been
injected into the blood-stream, while oxygen-carryingsolutions of various kinds have been tried. The intra-venous injection of oxygen, unless performed veryslowly, carries a severe risk of embolism. A different
type of experiment followed the demonstration byHartridge and Roughton that haemoglobin would take upoxygen much more readily in solution than when enclosedin the red cells. But as would be expected, animalsperfused with solutions of haemoglobin rapidly died asthe haemoglobin passed into the urine and lymph.Further attempts were based on the principle adoptedby nature in the lungs-the exposure of a thin film ofred cells of large surface area to oxygen. Perhaps themost outstanding experiments were those by Baylissand his co-workers 2 and later by Daly,3 but neither oftheir thin-film methods was suitable for maintainingan animal for long.The recent advances in intracardiac surgery have
stimulated renewed interest in cardiopulmonarymachines. In this issue Dr. Bjork describes one
which has been evolved in Professor Crafoord’s clinic
1. Dale, H. H., Schuster, E. H. J. J. Physiol. 1928, 64, 356.2. Bayliss, L. E., Fee, A. R., Ogden, E. Ibid, 1938, 66, 443.3. Daly, I. de B., Thorpe, W. V. Ibid, 1933, 79, 199.
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at the Sabbatsberg Hospital in Stockholm. The
superiority of this machine lies in the excellent oxygena-tion which is obtained by spinning a row of plates whichdip into a trough of blood, and so expose constantlychanging thin films of red cells to oxygen (or anaestheticgases if required). On the mechanical side the machine owesmuch to the work of Andersson, who was also responsiblefor the engineering aspects of the spiropulsator, whichProfessor Crafoord uses so successfully for giving anaes-thetics during thoracic operations. The oxygen uptakeof the blood in Bjork’s apparatus is much better thanin any previous machines, as much as 110 ml. of oxygenbeing added to each litre of blood per minute. Heparinis added to prevent clotting, but careful filtration of.theblood returning to the animal is essential to avoidembolic complications. There is a considerable break-down of red cells in such a machine, but it has beenelaborated sufficiently to maintain the oxygen require-ments of the brain of a dog for half an hour. It isknown that the aorta can be clamped distally to the leftsubclavian artery for half an hour without any significantdamage to the lower half of an animal, and thus byclamping the venae cavae the heart can be opened,relatively bloodlessly.The aim of these experiments is to isolate the human
heart from. the circulation while it is opened for operativeprocedures. This new work is a great step forward, butit leaves us a long way from this goal. This year analternative approach has been exploited by HolmesSellors 4 and Brock 5 in their operation for the relief ofpulmonary stenosis. Both have successfully thrust aninstrument through the wall of the right ventricle anddivided the constricting diaphragm in the beating heart.
VETERINARY PROGRESS
THE annual congress of the National VeterinaryMedical Association, held at Southport from Sept. 8to 15, once again illustrated the similarity betweenveterinary and human medicine in the urgent problemsof the moment. Tuberculosis, virus diseases, andsalmonella infections are all exercising the minds ofthose responsible for the control of communicablediseases, whether in animals or in man. Prof. T. Dalling,who became Chief Veterinary Officer in August, discussingthe control of tuberculosis in cattle, emphasised thatone of the chief difficulties in tuberculin-testing isthe non-specific sensitisation to mammalian tuberculin.Steps are being taken to increase the specificity of thecomparative intradermal test, in which avian andmammalian tuberculins are injected simultaneously atdifferent sites and the reactions compared. Extensive
experiments done on the specificity factors of P.P.D.
tuberculins produced from different acid-fast bacteriahave shown that twice as much avian P.P.D. is requiredto elicit the same reaction in bovine sensitisations asin human ; Green suggests that for this reason bovineP.P.D. might be more useful in the comparative testfor distinguishing between specific and non-specificinfections in cattle. Work is also being done on thechemical modification of tuberculins. In a large-scalefield experiment the double intradermal test as usuallycarried out proved to have no advantages, but workersin Northern Ireland have shown that 7 days after theinjection of tuberculin the site of injection develops anenhanced specific sensitivity. Less laborious and moreprecise methods of detecting bovine tuberculous infectionin cattle may arise from this work, but already theadoption of the single as opposed to the double intra-dermal tuberculin test has greatly increased the amountof testing that can be performed. Professor Dallingurged the importance of suitable callipers for measuring
4. Sellors, T. H. Lancet, 1948, i, 988.5. Brock, R. C. Brit. med. J. 1948, i, 1121.
skin thickness, and now that these are obtainable theyshould be widely used by the Ministry’s whole-time andpart-time staff. There are now over a million cattle,or 13-9% of the total cattle population, in attested herdsand 250,000 in herds licensed to produce T.T. milk, butvarious speakers demanded- a more vigorous policy oferadication.The salmonella organisms responsible for bacillary
white dianhoea in poultry and fowl typhoid seldomcause disease in man, but various new salmonella typeswhich may cause food-poisoning in man have latelybeen isolated from fowls, eggs, and animals. It hasbeen shown, too, that salmonella infection in cows andcalves is commoner than was generally realised.l In
poultry, salmonella infections call for an organisedprogramme of agglutination-testing and attention toincubator hygiene. Incubator infection is the chiefmethod, of spread through setting eggs, the shells ofwhich are infected by faecal contamination. Mr. J. E.Wilson, who discussed the control of these infections,described the technique of incubator fumigation in detail ;to forestall shell penetration it should be carried outas soon as possible after setting. In large outbreakshe recommended sulphonamide therapy in conjunctionwith other measures. Organisms which are sensitiveto sulphonamides, or to one of the antibiotics, will ofcourse be equally so, whether they are infecting man,animals, or birds ; but the behaviour of the antibacterialdrugs differs considerably in different species owing tovariations in absorption and excretion. Thus Mr. J.
Berger and Mr. J. Francis showed that, in domesticanimals, ’Sulphamezathine’ gives consistently higherblood-levels than equal doses of sulphadiazine ; whereasin man the reverse is true.2 ’
Mr. Horace Thornton, chief veterinary inspector,Newcastle-on-Tyne, contended that the standards ofmeat hygiene, inspection, and control are much lowerin Britain than in Continental and other countrieswhere the veterinary profession -has taken a greaterpart in the work. He advocated routine bacteriologicalexaminations in the inspection of borderline carcasesand a greater use of biochemical tests. The adoptionof such methods would result in the release of many ofthe carcases which, in Britain, are now totally con-
demned. The criteria now applied in Germany inrelation to tuberculous carcases deserve critical study.Some of his specific criticisms are set out by Mr. R. F.Montgomerie, PH.D., the association’s president, in ourcorrespondence columns. With regard to home-killedmeat, however, Mr. Harry Priestley s says- there is - nocause for alarm. It is a pity that animals are rarelyinspected before slaughter in Britain, although manydiseases which are difficult to detect in the dead animalcan readily be diagnosed in life. Several speakersregretted that the Ministry of Food has not regularisedthe slaughter of horses for food.
Encephalitis is as complicated a subject in dogs 4 asin man. Mr. A. B. Maclntyre, Dr. D. J. Trevan, andDr. Montgomerie showed that apart from dietary andmiscellaneous causes canine encephalitis is sometimesassociated with canine distemper and with a newlyrecognised virus infection which causes a characteristicthickening of the pad epithelium.On Sept. 10 the association visited Liverpool Univer-
sity and its Veterinary Field Station, where Prof. J. G.Wright described the techniques for csesarean sectionin the cow. In his view the incision should be madejust to the left of the midline, and not in the right fiank.Despite the weight of the abdominal contents he hasnot been troubled by postoperative rupture.
1. Field, H. I. Vet. J. 1948, 104, 251.2. See Vet. Rec. 1947, 59, 131 ; Vet. J. 1947, 103, 193.3. Manchester Guardian, Sept. 18, p. 4.4. Parry, H. B. Vet. Rec. 1948, 60, 389.
