Fibrinolysin for Treatment of Blood-clots in Man

624

nothing to its efficiency, but rather detract taking valuable time away from study and practice ". Although (or perhaps because) there are no formal associations to band them together, there is a

fession add from it by

great deal of

solidarity and cooperation among Russian doctors (other than party members); and now that political pressure on them has considerably abated, and international contacts seem rather easier, it will not be surprising if the profession regains some kind of

depopulation of the land, may take the Chinese much further towards Communism than the Russians have ever gone. Beside so vast a social change, the loss of£ a profession, of professional ideals, and of the scientific attitude may seem a small one. Nevertheless, in the long run, it would not be small at all. Treatment of Blood-clots in Man BLOOD-CLOTS are not permanent structures; they may serve as a supporting framework for invading fibroblasts

Fibrinolysin for

corporate life. Whereas differences between Soviet Russia and other industrial nations seem to be steadily diminishing, the

and capillary blood-vessels, but as these form new tissue the clot of fibrin disappears. The process of getting rid same may not be true of China. The Russians began with a radically Communist revolution, but by suc- of the fibrin-fibrinolysis-is now known to be brought cessive concessions to expediency have achieved a about by a proteolytic enzyme and its precursors in The active fibrinolysin is named tissues.l national Socialist State now possibly in process of being blood " this is present in blood in an inactive and plasmin ", " liberalised. The Chinese, learning by Russian experiform called plasminogen "; plasminogen activators ence, began with many compromises but now appear to in are blood, urine, and milk; trypsin can act as present be moving towards a more fundamental reorganisation is also a system of proactivators, and activator. There of their society. Among their compromises was the an of these is streptokinase. preservation of the Chinese Medical Association as the one of the best-known is still one of the serious causes of Thromboembolism embodiment of the medical profession; and doctors from this and other countries who have visited China medical and surgical morbidity and mortality. Once a clot has appeared, we prescribe anticoagulants in the at the invitation of the Association have been heartened by finding that so many of.its leading members have hope of preventing further clots, and this indeed is the the same medical interests as themselves and apparently basis of the anticoagulant treatment of coronary thrombosis.2 But such treatment is like shutting the door after want to belong to the same medical world. On the other hand, even last year, the issue was evidently in the horse has gone; tissue damage in the area blocked off the balance. The Chinese Medical Association has by the original clot continues unchecked. It would be if we could remove the clot or recanalise the very close links with the Government, and official better vessel as soon as possible, in addition to preventing statements about the value of guidance by the Communist party have not been in line with FIELD’S view extension or complication. Accordingly attention has (and ours) that " medicine, like other professions, is one been given to fibrinolytic agents, and recent American in which the scientific approach must predominate and reports suggest that a clinically useful fibrinolytic agent one which flourishes best in an atmosphere of free may have been prepared. Streptokinase was tested as a fibrinolytic agent 3; but inquiry, scepticism, and the search for facts rather than doctrine, dogma, or political considerations ". The streptokinase is not well tolerated and inhibitors were Association’s recent pronouncement on Anglo-American found commonly in blood. Intravenous trypsin has been aggression in Arab countries1 is depressing less because given a trial 4 : it activates plasminogen and has some of its content than because it uses the stock phrases of direct action on fibrin. But here again there were snags: Communist propaganda without so much as bothering antitryptic activity of plasma was found to be common; and the dose needed to produce an effect also interto translate them into the more objective language more persuasive to doctors and scientists. Even several years fered with other plasma-proteins, especially those con-a cerned with blood coagulation. MOSER5 has used ago, when he made the observations recorded on p. 633, Professor GouLD formed the impression that in the plasminogen prepared from the globulin fraction of Chinese struggle between science and dogma, science human plasma-protein. The plasminogen is activated to had already been defeated; and there is now more plasmin by streptokinase, which is subsequently removed; this active plasmin does not attack plasmareason to fear that he is right. If this fear is realised, however, we should still not make the mistake of under- proteins other than fibrinogen and fibrin. It had preshownto remove clots produced experiestimating what can be achieved by dogma, with tech- viously been dogs and rabbits; and now MOSER has nological aid; nor should we assume that what is thus mentally in on its use in 52 cases of thromboembolic reported achieved is necessarily interior. une 01 tne greatest disease in man, including 13 of cerebral thrombosis. sociological experiments of our time, if not of all time, is beginning with the Chinese Government’s new pro- Lyophilised material was provided for clinical use, and it could be kept at -4°C for several months. It was gramme for dividing their population into huge comassayed in fibrinolytic units "; 1 F.u. is the amount of munes in which men and women alike are to form al 1. Astrup, T. Lancet, 1956, ii, 565. labour force disposable between the tasks of agriculture 2. ibid. 1956, i, 559. 3. Tillett, W. S., Johnson, A. J., McCarty, W. R. J. clin. Invest. 1955, 34, and industry.2 This scheme, which has the merit of 169. avoiding the concentration of industry in cities with 4. Taylor, A., Overman, R. S., Wright, I. S. J. Amer. med. Ass. 1954, 155, ,

"

347.

1. Chinese med. J. August, 1958. 2. Manchester Guardian, Sept. 11,

1958, p. 1 and 7.

5. 6.

Moser, K. M. ibid. 1958, 167, 1695. Grossi, C. E., Cliffton, E. E. Surgery, 1955, 37, 794.

625

preparation which will change the turbidity of a standard fibrinogen-thrombin clot by 50% in ten minutes. Clinical doses varied from 30,000 F.u. to 90,000 F.U., the dose being increased as experience confirmed the safety of the substance; the lyophilised material was dissolved in 500-1000 ml. of 5% dextrose solution and infused over two to four hours. This material nearly always provoked a febrile reaction six to eight hours after the infusion, but any symptoms could be ameliorated by giving an anti-histamine drug; there was 1 case of generalised urticaria and 1 of local erythema. There was no effect of any of the blood-coagulation tests. Plasmafibrinogen estimations showed that a small loss had occurred six hours after a dose of plasmin, but values were normal again in twenty-four hours. There were no haemorrhages even in patients having anticoagulant treatment. The fibrinolytic activity of the patient’s reached a maximum three hours after an infusion plasma of plasmin; 30,000-50,000 F.u. raised the activity by 30%, and 70,000-90,000 F.u. produced a rise of 40%. The best results were obtained with peripheral venous thrombophlebitis and pulmonary embolism. 18 patients with deep venous thrombophlebitis were treated; most of them showed loss of heat and tenderness and decreased swelling within twenty-four hours, and within seventy-two hours the affected part returned to normal; the phlebitis did not recur when the patient got out of bed, and pulmonary embolism did not occur after the treatment. Experience with 12 cases of peripheral arterial occlusion was less encouraging; no patient Of 14 patients with cerebral was certainly relieved. arterial occlusion there was maintained improvement in 4, transient improvement in 3, and no effect in 7; MoSER considers that from this small group no definite conclusions can be reached, but there was no evidence that any patient deteriorated, and the infusions could be given with safety. In coronary thrombosis not enough patients have yet been treated to decide whether fibrinolysin will be useful. SUSSMAN and FITCHused the same preparation of plasmin as MOSER for the treatment of 3 patients with cerebral arterial occlusion. In 1, with occlusion of an anterior cerebral artery, there was no effect. In another, aged 75, with hypertension, a left carotid arteriogram showed occlusion of the internal carotid artery just beyond the bifurcation of the common carotid artery; infusions of plasmin into the left carotid artery produced some clearing, but there was no clinical improvement. In the 3rd patient, who had occlusion of the middle cerebral artery, the block was relieved after plasmin infusions and there was some clinical improve-

fibrinolysin treatment should be followed by anticoagulant treatment, and for how long. The American workers used a plasmin preparation that was commercially available, and it should not be difficult for a similar preparation to be made in this country. know whether

Decline of the

Father-image

THE increase in crime during the past few months is worrying everyone, and rightly so, for, however critical one may be of Home Office statistics, the present crimewave must be accepted as real and disquieting. Yet its cause remains as obscure as the cause of crime itself. From a psychological standpoint, it is easy to agree that a defect in the super-ego plays a large part in inducing criminal behaviour, and to accept FREUD’s thesis that the super-ego is formed by parental and other authority, and is the repository of morals, prohibitions, conscience -in fact, of the sense of right and wrong. But it is less easy to define the super-ego precisely, and still harder to pick out the influences which determine its function for better or for worse. Recent studies of this problem include two investigations using the thematic apperception test and have provided some tentative information. (The test consists -in asking the subject to tell a story round each of a series of pictures showing situations of differing emotional flavour.) In Australia LYLE and GILCHRISTcompared the results it gave in groups of delinquent and normal boys, and in the United States JENSENapplied it to groups of boys showing extremes of aggression and passivity. The amount of aggression shown by all the boys did not greatly differ, but delinquent and aggressively antisocial boys related stories of " naked " whereas the normal and the passive groups aggression, " buffered " their fantasies of violence with just retribution, suicide of the malefactor, and mitigating factors such as stealing for a starving family or acting under hypnosis. Analysis of stories according to some other criteria showed, surprisingly, no significant differences among the groups. Thus references to murder, robbery, intra-family tensions, feelings of rejection, love, and loyalty, were evenly distributed between the groups. But socially taboo aspects of sex, violence, and language were more common in the stories of the antisocial boys. The difference between the groups was not in aggressiveness itself, but in their social attitude towards it: the antisocial groups showed a lack of guilt-reactiona defect, in fact, of the super-ego. These studies still leave open the reasons for this psychological defect, and people tend to put forward ment. unverified suggestions which vary according to the These results suggest that it is worth obtaining further ethical, religious, social, or political tub which they experience with plasmin preparations, especially in the happen to be thumping. But the reasons lately put forward by GALDSTON3 deserve careful consideration. He treatment of superficial and deep thromboses of leg veins. The results in cerebral vascular disease have so lays the blame on the decline of the family, and particufar been disappointing, but in this group of disorders we larly the change of orientation within it. Writing of the have so little effective treatment that even not very United States, he describes the cult of " momism and promising methods are worth testing. We still need more suggests that American society has swung from a patinformation on toxicity and on dosage; and we need to 1. Lyle, J. G., Gilchrist, A. A. Brit. J. med. Psychol. January, 1958, p. 51. "

7.

Sussman, B. J., Fitch, T. S. P. J. Amer. med. Ass. 1958, 167, 1705.

2. 3.

Jensen, A. R. Psychol. Monogr. 1957, 71, 13. Galdston, I. Ment. Hyg. 1958, 42, 229.