931

acceleration is not due to the lecithin itself. PooLE

and ROBINSON 20 21 showed that ethanolamine phos-phatide (which has the same chemical constitutionas lecithin, except that the amino-alcohol ethanola-mine replaces the choline in the molecule) has thesame action as the crude lecithin preparations onthis blood-clotting system. Rat chylomicra alsoaccelerated the clotting. Both chylomicra andethanolamine phosphatide (prepared from brain)greatly increase, in an apparently similar manner,the formation of thrombin in the coagulation system ;and acid hydrolysates of rat chyle contain a substanceresembling ethanolamine in its- ionophoretic and

chromatographic behaviour. In a subsequent paper 22the effects, on thrombin formation, of ethanolaminephosphatide prepared synthetically are comparedquantitatively- with the effects of ethanolamine

phosphatide prepared from brain and egg-yolk.The results leave little doubt that ethanolaminephosphatide itself is responsible for the enhancedrate of thrombin formation, no activity being shownby the related serine and inositol phosphatides. Ithas been known for some time that, in man, a fattymeal promotes blood-coagulation,23 and O’BRIEN 24has lately shown that this shortening of the clotting-time is probably mainly due to an increase inethanolamine phosphatide : indeed, he has attemptedassessment of the " phosphatidyl equivalent " of

plasma after different types of meal. BARKHAN,NEWLANDS, and WILD 25 have examined the effectsof chemical fractions of human brain tissue (contain-ing phospholipid material) on coagulation systems.One such fraction, which was probably phosphatidylethanolamine, was an accelerator, but another was aninhibitor. The latter was, they thought., phosphatidylserine; and in ascribing an inhibitory effect to thissubstance they seem to differ from the Oxford workers.MACLAGANand BILLIMORIA 26 have shown that, duringalimentary absorption of fat in man, clotting-time maybe greatly reduced. Whereas butter had a powerfulaction, margarine had very little ; yet the two fatsproduced plasma turbidity of the same order. Theysuggest that the acceleration of clotting is not entirelydue to chylomicra as such, but to a closely relatedgroup of phospholipids abundant in milk and milkproducts.The full implications of these exciting facts are of

course still far from clear, and the problem is beingstudied in many different laboratories. The Oxfordinvestigators have described some of the componentsof the system which may be responsible for theremoval of chylomicron-fat from the circulation, butthey are scrupulously careful to avoid the assumptionthat what happens in experiments in vitro necessarilyhappens also in the body. Nevertheless the linksbetween blood-coagulation and the disturbancesin fat transport known to exist in coronary-arterydisease give us reason to hope that they are elucidatingthe essential chemical pathology of this disorder.Once this is understood, rational preventive measuresmay be practicable.20. Poole, J. C. F., Robinson, D. S. Ibid, 1956, 41, 31.21. Robinson, D. S., Poole, J. C. F. Ibid, p. 36.22. Poole, J. C. F., Robinson, D. S. Ibid, p. 295.23. Fullerton, H. W. Davie, W. J. A., Anastasopoulos, G. Brit. med.

J. 1953, ii, 250.24. O’Brien, J. R. Lancet, Aug. 4, 1956, p. 232.25. Barkhan, P., Newlands, M. J., Wild, F. Ibid, p. 234.26. Maclagan, N. F., Billimoria, J. D. Ibid, p. 235.

Arterial Necrosis Following Resection ofCoarctation of the Aorta

To the pathologist, focal arterial necrosis is aninteresting lesion, partly because of its associationwith a considerable number of rare and apparentlyunrelated diseases of unknown origin, but mainlybecause in hypertension its presence enables him tosay that the disease has entered the malignant phase.Though its pathogenesis is not yet entirely clear, thereis some evidence 1 that it is related to arterial spasm ;and the fact that necrosis is never seen in the vesselsof a kidney whose renal artery has been constrictedby a Goldblatt clamp 3 4 has persuaded most studentsthat in hypertensive disease it is a direct local resultof excessive intra-arterial tension. In normal rats,it has been provoked by brief overdistension of thearterial tree with saline.5

If this simple explanation of arterial necrosis is

correct, the clinician might reasonably expect necrosisto occur whenever arteries (normal or hypoplastic) aresuddenly exposed to the full force of a high blood-pressure. These conditions are exactly fulfilled bysuccessful plastic operation for coarctation of theaorta, and much interest therefore attaches to

BENSON and SEALY’S 6 report of two cases in whichgross arterial necrosis did in fact follow this operation.

Their first patient was a man of 22 with a combinationof coarctation and aortic incompetence. The intra-arterial pressure in the brachial and femoral arterieswas 240,60 and 90 60 mm. Hg respectively. Afterresection of the coarctation the brachial pressure remainedhigh (190/80) and strong pulsation was felt in the femoralarteries. On the third postoperative day the patientcomplained of severe abdominal pain and this was laterfound to be due to infarction of most of the small intestine.Post mortem, evidence of haemorrhage and necrosis wasalso found in the stomach, liver, and kidney. But themost striking change was widespread acute necrosis ofthe arterial system distal to the coarctation, includingthe intercostal, splenic, renal, mesenteric, and gastricarteries, and even the common iliac arteries and theaorta. The necrosis was mostly in the plain muscle ofthe media and there was little cellular reaction.

Their second patient was a 4-year-old child whosebrachial and femoral blood-pressures were 150/80 and98/65 mm. Hg respectively. After operation the brachialpressure remained unchanged but the femoral rose to225/180. Here again acute abdominal symptomsappeared, and 24 inches of gangrenous ileum was resected.The child recovered from the second operation and seemedwell two months later. Extensive medial necrosis wasfound in the arteries of the excised loop of intestine.

BENSON and SEALY refer to three other cases in therecent literature and point out that less severe

examples of the complication have probably beenoverlooked. In this connection it is noteworthy thatin their report a few weeks ago on forty cases ofcoarctation treated surgically CLELAND et al. saythat " in five cases abdominal pain in the postoperativeperiod was severe enough to cause concern."

These cases are important for two reasons. As theclinical counterpart of the experimental evidence wehave mentioned, they provide strong support for thecurrent view that hypertensive arterial necrosis is a1. Ellis, A. W. M. Arch. intern. Med. 1949, 84, 159.2. Byrom, F. B. Lancet, 1954, ii, 201.3. Wilson, C., Pickering, G. W. Clin. Sci. 1938, 3, 343.4. Goldblatt, H. F. J. exp. Med. 1938, 67, 809.5. Byrom, F. B., Dodson, L. F. J. Path. Bact. 1948, 60, 357.6. Benson, W. R., Sealy, W. C. Lab. Invest. 1956, 5, 360.7. Cleland, W. P., Counihan, T. B., Goodwin, J. F., Steiner, R. E.

Brit. med. J. Aug. 18, 1956, p. 379.

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direct result of excessive filling tension. At the sametime they raise the question of what steps should betaken to prevent this complication in future. Theoccurrence of arterial necrosis, and its extent, pre-sumably depend on how high and how abruptly thepressure rises in the distal vessels when the obstructionis relieved, and on how long the high pressure persists.Exact information on the relative weight of thesethree factors is -not available, but the experimentalevidence shows that sudden exposure to a sufficientlyhigh filling tension may- cause irreparable damagealmost immediately. Presumably, therefore, in orderto avoid this potentially disastrous complication, theblood-pressure will need to be carefully controlled byhypertensive drugs before and during the operationand perhaps for some considerable time afterwards.

Annotations

THE POSTGRADUATE SCHOOL COMES OF AGE

SINCE it was opened in 1935, over 12,000 studentshave attended the Postgraduate Medical School of

London, 2000 of them coming from outside the Common-wealth. Known originally as the British PostgraduateMedical School, and a school of London University,it has from the first been associated with the Hammer-smith Hospital, which until 1948 was administered

by the London County Council. The British Post-

graduate Medical Federation was formed at the end ofthe war, and the teaching organisations in the sub-

specialties, such as ophthalmology, neurology, and

laryngology, already established at appropriate hos-

pitals in London, combined as the constituent institutesof the Federation.As usual in the history of knowledge, research and

teaching go hand in hand, and the outstanding work ofthe staff of the school is known all over the world. It isdifficult, and perhaps unfair, to single out examples ofthe very many investigations undertaken, but mentionmust be made of the pioneer work at the school on cardiaccatheterisation and liver biopsy, and the studies ofcardiac output, pulmonary hypertension, mitral-valvesurgery, and the neurological complications of hepaticdisease. Plasma-proteins, phosphatases, haemolytic andmegaloblastic anaemias, peripheral arterial disease, andbacterial genetics are among the special interests of thedepartment of pathology and bacteriology ; and veryrecent experiments in the production of an effective

staphylococcal vaccine are especially interesting in viewof the increasing resistance of staphylococci to antibiotics.Work on the crush syndrome and the treatment of anuriahas led to the saving of many lives, and the school hasalso led the way in cesophageal surgery. Other diverseand useful research has included evaluation of the drugtreatment of high blood-pressure and tuberculosis, andstatistical studies of the relationship between the ABOblood-groups and disease.The law of diminishing returns applies to the cost of

research. The medical explorer of today is less likely thanhis forerunners to make his discoveries by simple clinicalobservation and experiment alone, and depends more andmore on such expensive tools as radio-isotopes and thedevices which measure them. For such work new andbigger laboratories are needed, and in their annual reportsthe departments of surgery and pathology of the Post-graduate Medical School both complain of having toolittle space. The school was built at a time when moneywas very scarce and it needs better classroom and libraryaccommodation. The committee of management there-fore now hope to complete the school-at an estimated

cost of £750,000-and their appeal brochure includesan architect’s drawing of the buildings: proposed,which comprise lecture-theatres and common-rooms,joined by a bridge to a 9-storey block of laboratories witha library. Unlike the famous undergraduate schools, thePostgraduate Medical School has neither endowments norsubscribers, and depends chiefly on a grant from LondonUniversity, only 3% of its funds being derived fromstudents’ fees. No capital is to hand for new buildings,and an appeal to raise the required sum is launched thisweek. All who have learnt from the work done at

Hammersmith, and all who have been helped by it,have reason to lend their aid.

1. Volhard, F., Fahr, T. Die Brightsche Nierenkrankheit. Berlin,1914.

2. Luetscher, J. J. clin. Invest. 1950, 29, 1576.3. Squire, J. R. Brit. med. J. 1953, ii, 1389.4. Epstein, A. A. J. exp. Med. 1914, 20, 334.5. Pollak, V. E., Pirani, C. L., Kark, R. M., Muehrcke, R. C.,

Vincent, C. F., Nettles, J. B. Lancet, July 14, 1956, p. 59.6. Rosenheim, M. L., Spencer, A. G. Ibid, Aug. 18, 1956, p. 313.7. Harrison, C. V., Milne, M. D., Steiner, R. E. Quart. J. Med. 1956,

25, 285.8. Blainey, J. D., Hardwicke, J., Whitfield, A. G. W. Lancet, 1954,

ii, 1208.

NEPHROSIS AND RENAL-VEIN THROMBOSIS

A FEW years ago the " nephrotic syndrome wasdebatable territory ; some thought that it usually meantnephritis in the sense of Ellis’s type 11, or a late subacutedevelopment of type i, while others held that it was adisorder sui generis, the genuine nephrosis of V olhard andFahr.1 It was realised that recovery was occasionallypossible, especially in children, and some claims weremade that cortisone might promote recovery 2; in fact,investigations of the response to cortisone and cortico-trophin (A.C.T.II.) still continue.A detailed study of the nephrotic syndrome has shown

that it is far from uniform in its pathogenesis. The workof Squire 3 has reinforced the older view of Epstein 4that excessive urinary protein loss is the common factorwhich sets off the train of events towards a nephroticsyndrome. Excessive proteinuria and a clinical andbiochemical picture of nephrosis are the result of glo.merular lesions in (1) glomerulonephritis, (2) diabeticintercapillary glomerulosclerosis (Kimmelstiel-Wilsonlesion), (3) amyloid disease, (4) the " wire-loop " lesionsof disseminated lupus erythematosus, and (5) trimeth-adione and inorganic mercury intoxication. In addition,Pollak and his associates have shown by biopsy thatthere is a reversible glomerular lesion in the albuminuricoedema of pregnancy (eclampsia). It is even possible toextend the definition further to include protein loss fromthe prolonged venous congestion of constrictive peri.carditis and other forms of chronic heart-failure Thoughat this point the borderland with other syndromes ofoedema becomes blurred, this functional physiologicalapproach to the problem is of much more than academicinterest. The treatment given by Rosenheim andSpencer 6 at University College Hospital (dietetic meas.ures to maintain a positive nitrogen balance, the removalof oedema by low-sodium diet, and the oral administrationof resins) led to a gratifying disappearance of all nephroticmanifestations in 6 out of 13 patients.

Harrison et al. discuss renal-vein thrombosis as a

cause of the nephrotic syndrome, of which it may repro-duce all the clinical and biochemical features.s Underconservative treatment, the occluded veins mayrecanaliseor capsular collaterals develop, with apparent recovery,though renal function remains slightly impaired. Throm-bosis of the renal vein is usually a complication ofthrombosis of the inferior vena cava-either fromupward extension from the leg veins, or in associationwith invasion of the vena cava by hypernephroma orby malignant coeliac glands. Another type is renal-venulethrombosis which can complicate nephritis or amyloidnephrosis, producing sudden deterioration of renal fune-