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used. The evidence suggests that the temperatecigarette-smoker, who confines himself to, say, oneafter each meal or to two or three in the evening, runsan appreciably lower risk. Two hundred years ago"

drunkenness was the acknowledged national vice ofEnglishmen of all classes." 5 Today, to drink whiskyfrom a hip-flask in a suburban train on the way towork is socially unacceptable. Maybe to smoke acigarette at such a time will in due course also bedeemed a social impropriety. If so, the communitywill be the healthier.

5. Trevelyan, G. M. English Social History. London, 1942.6. Barcroft, J. Researches on Pre-natal Life. Oxford, 1946.7. Acheson, G. H., Dawes, G. S., Mott, J. C. J. Physiol. 1957,

135, 623.8. Walker, J. J. Obstet. Gynœc., Brit. Emp. 1954, 61, 162.9. MacKay, R. B. Ibid, 1957, 64, 185.

10. Randall, C. L. Amer. J. Obstet. Gynec. 1957, 73, 931.

The Newborn Infant’s Oxygen-supplyTHE newborn infant, deprived of the placental

circulation, will die unless by his own efforts he canproduce and maintain a higher level of oxygenationthan prevailed in the later phases of intra-uterinelife. The immediate adjustments of post-natal lifeare directed to this end and are primarily concernedwith establishing adequate pulmonary ventilation andensuring that the brain, rather than the liver, receivesthe best-oxygenated blood.The fundamental work of BARCROFT 6 showed that

in pre-natal life the foetus elaborates the centralnervous organisation required for breathing, whichnormally is inhibited until required for pulmonaryrespiration. Release from inhibition occurs eitherbecause of the inflow of new sensory stimuli at birthor by hypoxic depression of the inhibitory centres.AcgESOrr et al.’ have extended this work using, likeBARCROFT, the sheep. In a study of oxygen con-sumption in foetal and newborn sheep they haveshown that there exists a remarkable, but limited,capacity to adjust the oxygen need in relation to thesupply. In the latter half of pregnancy adequateoxygenation can be maintained only by great increasesin umbilical blood-flow. If the placenta is insufficientor the compensatory mechanisms in the foetus fail,the survival of the foetus depends entirely on itstolerance to anoxia. That similar mechanisms

operate in human pregnancy seems likely from thework of WALKER s and RACHEL MACKAY, who haveshown a progressive fall in oxygen saturation of theumbilical-cord blood as pregnancy proceeds to termand, especially, beyond. A similar fall is found whenpregnancy is complicated by pre-eclamptic toxaemia.Some of the clinical facets of placental insufficiencyhave been discussed by RANDALL.LO

Placental circulatory failure with decompensationof the foetus will cause, in severe cases, intra-uterinedeath. Lesser degrees of hypoxia may initiate intra-uterine gasping movements which, if associated withmeconium-stained liquor amnii, produce asphyxiaand meconium pneumonitis. The anoxic infant isborn with an inadequate oxygen reserve and a

depressed nervous system-two factors which greatlydecrease its ability to attain adequate pulmonaryventilation. More acute lowering of foetal oxygenationis found in cases of abnormal delivery ; interruptionsof placental blood-flow, as in placenta praevia andprolapsed cord ; and interference with the oxygen-

supply to the placenta by general or spinal anaesthesia.HENDERSON et al.11 point out that, while all thesefactors produce a measurable lowering of umbilical-vein oxygen saturation, this is not necessarily a goodguide to the clinical state of the infant. Some infantsat birth may survive with extremely low cord-oxygensaturations, whereas others with mildly reduced oxygensaturations are severely asphyxiated. This is to be

expected in view of the limited value of a singlesampling of cord blood and the many traumatic andchemical factors which influence the first hours of ababy’s life.

After birth the majority of infants rapidly attaina near-adult arterial oxygen saturation.12 2 SHIELDSand TAYLOR 13 have shown that infants born aftercomplications of pregnancy, heavy maternal analgesia,or operative delivery are considerably slower in achiev-ing a normal saturation, determined by a contin.uous-recording ear oximeter. Further studies on the linesof those reported by CROSS et al.14 are needed in orderto elucidate the special metabolism of the newbornand its powers of survival in low oxygen levels.

Possibly other factors are more important than

oxygen saturation in determining the clinical con-

dition of the newborn and the eventual prognosis.One of the other factors is the circulatory status of thenewborn. The neonatal circulation plays an importantpart in producing lung expansion and also ensurespreferential oxygenation of the brain. ADAMS andLiND,15 by cardiac catheterisation, have demonstrateddirectly the persistence of a patent ductus arteriosuswith a predominantly left-to-right shunt in the firstfew days of life. Dr. GUNTHER 16 has attempted torelate the complicated circulatory adjustments afterbirth with the changes in blood-volume consequenton occlusion of the cord and the later development ofpulmonary syndrome. Early clamping of the cord orelevation of the infant while the cord is still attachedto an atonic uterus will deprive the infant of much ofhis blood-volume. This will be of greatest importancein premature babies, who have a relatively largerproportion of blood in the placenta, and in babiesdelivered by caesarean section. It is just these twoclasses of infants that are susceptible to pulmonarysyndrome or, as it is better known, hyaline membranedisease. BROWN 17 has already drawn attention tothe possible connection between early clamping of thecord and the onset of hyaline membrane disease. Sofar, the arguments for this association are largelytheoretical. Dr. BONHAM CARTER,18 summarisingrecent advances in this field, has ingeniously relatedthe changes immediately after birth with the respira-tory difficulties of early neonatal life. It should notbe difficult to devise a controlled study to demonstratethis relationship. It is now generally, although notuniversally, accepted that hyaline membranes are

formed from pulmonary exudate, probably as a resultof pulmonary congestion or hypertension.19 Early11. Henderson, H., Mosher, R., Bittrich, N. M. Ibid, p. 664.12. Smith, C. A., Kaplan, E. Amer. J. Dis. Child. 1942, 64, 843.13. Shields, L. V., Taylor, E. S. Amer. J. Obstet. Gynec. 1957,

73, 1011.14. Cross, K. W., Tizard, J. P. M., Trythall, D. A. H. Acta pœdiat.,

Stockh. 1957, 46, 265.15. Adams, F. H., Lind, J. Pediatrics, 1957, 19, 431.16. Gunther, M. Lancet, June 22, 1957, p. 1277.17. Brown, R. J. K. Ibid, Jan. 19, 1957, p. 163.18. Bonham Carter, R. E. Ibid, June 22, 1957, p. 1292.19. Gitlin, D., Craig, J. M. Pediatrics, 1956, 17, 64.

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clamping of the cord might well lead to pulmonaryhypertension as the rise in systemic blood-pressureconsequent on the increased peripheral resistance willbe transmitted via the patent ductus arteriosus to thelargely unopened pulmonary vessels. It is moredifficult to see how the reduced blood-volume con-sequent upon siphonage would operate. Certainly,expansion of the lungs might be delayed ; but the

picture of hyaline membrane is one of obstructive

dyspnoea, emphysema, and secondary collapse ratherthan of primary atelectasis. Nor do infants bornexsanguinated from acute blood-loss show clinical orpathological evidence of hyaline membrane.Whatever the truth concerning this hypothesis, it is

salutary to review continually the management of thenewborn in relation to newly discovered physiologicalfacts. The tragedies of retrolental fibroplasia and ofkernicterus of prematurity due to excessive dosagewith a vitamin-K analogue are stern reminders thatwe fail to do so at the infant’s peril.

1. Lancet, 1956, i, 559.2. Honey, G. E., Truelove, S. C. Ibid, June 8, 1957, p. 1155 ;

Ibid, June 15, 1957, p. 1209.

Second Thoughts on AnticoagulantTreatment for Coronary Disease

JusT over a year ago we reviewed current views onthe value of anticoagulant treatment in acute coronarydisease and drew attention to the conflict of opinionbetween those who, like GILCHRIST in Edinburgh andIRVING WRIGHT in New York, believed that everypatient should be given the benefit of anticoagulanttreatment, and those who, like RUSSEK and ZOHMAN,consider that such treatment should be reserved forthe " poor risk " patient. The choice between thesetwo views is important because, if the first group areright, it would be logical to send to hospital everypatient who is fit to be moved so that anticoagulanttreatment can be begun without delay ; whereas ifthe second group are correct it would be best for the" good risk" patients to be kept at home. Theburden of the anticoagulant treatment on hospitalaccommodation and laboratory facilities has alreadybecome considerable and coronary thrombosis is nowone of the commoner causes for admission to hospital.The two papers from Oxford by Dr. HONEY and

Dr. TRUELOVE which appeared in two of our recentissues 2 bear directly on this problem, since they haveexamined afresh the question whether anticoagulanttreatment does in fact improve the prognosis of acutemyocardial infarction, and how far the large expendi-ture of time, energy, and money on the admission tohospital and the laboratory control of treatment is

justified by results. They have made an elaborateanalysis of the results of 543 admissions (involving506 patients) to the Radcliffe Infirmary at Oxford inthe years 1940-54. They took an arbitrary time ofeight weeks from onset to represent the acute phase,and succeeded in tracing all but 1 of the 348 patientswho had survived beyond this phase. The period ofthe survey spans the introduction of anticoagulanttreatment at the hospital in 1948, and since 19513 out of every 4 patients have received this treatment.In their series of patients there were twice as manymen as women ; two-thirds of the men were aged50-70, two-thirds of the women were aged 60-80.

Women of equal age have a better chance of survivalthan men ; but fatality increases with advancing yearsand these two opposed effects cancelled out, so it wasnot necessary to differentiate between the sexes.

Surprisingly, there was no appreciable difference inmortality-rate between those patients who were

admitted in their first attack and those who had aclear-cut history of a previous infarction. The fatality-rate was unaffected by a previous history of anginaof effort, or hypertension. It seems to make nodifference whether the attack occurs during exertionor comes on at rest. The really bad prognostic findingsare, as so many physicians have emphasised, thepresence of early shock and hypotension.HONEY and TRUELOVE have examined very critic-

ally the data about their patients treated or not treatedwith anticoagulants and conclude that their figuresshow that anticoagulants

" have had only a smallbeneficial effect on the fatality of myocardial infarc-tion." They calculate that in the period 1952-54,when anticoagulants were extensively used, out of263 admissions only 11 lives were saved by this treat-ment-i.e., the mortality was 11 lives less than wouldhave been expected from previous experience with263 cases of the same clinical characteristics. Exami-nation of post-mortem records showed very clearlythat the reduction in deaths accompanying anti-

coagulant treatment was largely due to the eliminationof pulmonary embolism as a cause of death. Before

anticoagulants were used, 6% of the patients whosurvived the first forty-eight hours after onset diedfrom pulmonary embolism ; in 1952-54 only 1% died.HONEY and TRUELOVE consider that their figures showthat " anticoagulants do not have any major influenceupon the course of an established myocardial infarctper se, although they save some lives by removingalmost completely the dangerous complication of

pulmonary embolism." These conclusions are indeedin striking contrast to those of IRVING WRIGHT andthe American Heart Association’s survey, and tothose of GILCHRIST and his associates in Edinburgh.IRVING WRIGHT has restated his opinion,3 supportedby many others, that " if a patient suffers from adefinite myocardial infarction, if there are no contra-indications and if good facilities are available, heshould receive anticoagulant therapy." HONEY andTRUELOVE’s answer to these claims is that the figureson which they are based have not been adequatelyanalysed and, in particular, insufficient attention hasbeen paid to bias in the selection of patients whichhas the effect of exaggerating good results-by thisthey mean the tendency to allot relatively poor riskpatients to the " control " untreated groups. Theypoint out that bias in selection of this type can beshown to account for previous good results reportedfrom their own hospital with the same patients in theperiod 1948-51.

In their second paper HONEY and TRUELOVEassembled facts about the long-term prognosis, derivedfrom their well-observed group. They found that1 patient in every 10 admitted died within forty-eighthours, and one-third of the patients were dead by theend of the eighth week ; after two years had elapsedhalf the original patients were dead. Thereafter therisk of dying diminishes ; another 10% died in the

3 Wright, I. S. J. Amer. med. Ass. 1957, 163, 918.