Phosphatases and Prostatic Carcinoma

674 doctors should withdraw from the National Health

Service. The words " withdrawal from the service " are being used in two different senses which need sharp distinction. The kind of withdrawal which we for our part think both mistaken and professionally wrong is temporary : like the industrial strike, it is an interruption of normal work lasting only till one or other side gives way ; and when directed against a Goverhment it is the the

community by objection does not, of course, arise when withdrawal is not being used politically ; and there need be nothing unprofessional in doctors leaving the N.H.S., either individually or en masse, provided their notice is sufficient attempt to impose terms on extra-parliamentary means. But an

and their decision is irrevocable. of the

operation,

some

people

same

As to the purpose are

now

talking

as

though little. " direct action " will not only make the Government pay what is claimed but also make them change the service in some beneficial (though usually unspecified) way. Others, who have disliked the N.H.S. from the start, see this as the moment when a new MosES should invite his people to follow him out of bondage. Before accepting such an invitation, however, general practitioners may well ask for detailed information on life in the wilderness, and they should consider, soberly rather than in anger, the nature of their present discontent. Apart from the dispute about money, this discontent arises chiefly from a feeling that the relationship of doctor and patient is no longer what it was, and that organisation has made medicine less enjoyable than in the days of purely private practice ; also that it favours mediocrity and impedes progress. We may note, however, that in so far as this is true it is not peculiar to the British system : not long ago an American authority was saying that insurance schemes in the United States have altered the relationships of doctors, patients, and hospitals, which are now on a less personal basis 4 ; and in a lecture to students another American teacher has been speaking of present mediocrity " and a degeneration of motive in which " achievement becomes less impelling than security." Very possibly the capitation fee is not in fact the best means of paying the family physician 2 ; but even so, its disadvantages cannot all be laid at the door of our Governmental oppressors, since it is the method which the profession itself has preferred to maintain.5 Given a cessation of the cold war which has been doing so much harm to the service, profession and Government should be able to consider seriously together what alterations in such arrangements can and should be made. That even without such radical alterations there are big opportunities for improving general practice within the service has been proved by the enterprising minority of family doctors who have latterly done so much to raise its standards and increase their satisfaction in their work. Meanwhile, exacerbation of the cold war must damage not only the service but-even more-the profession. From deep conviction, the B.M.A.’s chairman of council ominously insists that, for the sake of medicine and our children, every practitioner must agree to withdraw : complete unity and loyalty are essential.s a

"

4. New York Times, Feb. 17, 1957. 5. See Medical World Newsletter, March, 1957. 6. See Times, March 25, 1957.

But, from conviction as deep, many will decline to support a course which, whatever its immediate rewards, cannot but be ultimately harmful. Today

general public still pays the profession the compliment of seeing something amusing, because incon. the

gruous, in the action recommended by the B.M.A.: there can hardly be a doctor in the country who has not had to suffer the greeting of some humorist: " Hullo doctor ! You on strike ? " But if current emotion prevails over traditional wisdom, and practitioners follow the fashion of industrial disputes, such action will never seem incongruous again ; and one of our most valuable if least ponderable possessions will have been lost. Instead, the real need now is twofold - that the Government should restore confidence in the Government and that the profession should restore confidence in the profession. Only then will they be able to work together to the same important ends.

and Prostatic Carcinoma ENZYMES which split organic phosphates and are most active around pH 5-"acid phosphatases "are present in many human tissues, but their concentration in the adult prostate is several hundred times greater than in other organs.1 This high prostatic level is not present before puberty, and has been demonstrated only in man and monkeys, and to a lesser degree in dogs ; it is not found in cats, rabbits, guineapigs. or rats.2 In human seminal fluid, acid-phosphatase levels are even higher than they are in the prostate.2 The physiological function of this enzyme is unknown, but, as we noted earlier,3 the acidity which is most favourable for its action corresponds to that of the vagina at the time of ovulation. The subject of prostatic acid-phosphatase levels in serum is complicated by differences in methods of assessing activity and in the range of phosphatases measured. Not all of the acid phosphatase in the serum comes from the prostate. Of particular importance is the red-cell acid phosphatase, the serum level of which rises sharply if haemolysis occurs. The

Phosphatases

method of ABUL FADL and KING4 involves ina,ctivation of this fraction, but not of the prostatic fraction, by formaldehyde. ABUL FADL and KING5 also reported the almost specific inactivation of prostatic acid phosphatase by L-tartrate-a means of differentiation which has been found to be of value6 but has not yet been so widely used as their formaldehyde method. In 1938, GUTMAN and GUTMANdescribed raised serum-acid-phosphatase levels in patients with prostatic carcinoma; and their work has been confirmed and extended by many others. 8—13 Using the formaldeliyde method, MERIVALE 12 found that 22 out of 23 patients with carcinoma of the prostate had serum levels above 3 units per 100 ml., 15 of them above 1. 2.

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Kutscher, W., Wolbergs, H. Hoppe-Seyl. Z. 1935, 236, 237. Sullivan, T. J., Gutman, E. B., Gutman, A. B. J. Urol. 1942, 48, 426. Lancet, 1945, i, 790. Abul Fadl, M. A. M., King, E. J. J. clin. Path. 1948, 1, 80. Abul Fadl, M. A. M., King, E. J. Biochem. J. 1949, 45, 51. Ozar, M. B., Isaac, C. A., Valk, W. L. J. Urol. 1955, 74,150. Gutman, A. B., Gutman, E. B. J. clin. Invest. 1938, 17, 473. Huggins, C., Scott, W. W., Hodges, C. V. J. Urol. 1941, 46, 997. Wray, S. Lancet, 1945, i, 783. Woodard, H. Q. Cancer, N.Y. 1952, 5, 236. Herbert, F. K. Quart. J. Med. 1946, 15, 221. Merivale, W. H. H. Guy’s Hosp. Rep. 1951, 100, 223. Wray, S. J. clin. Path. 1956, 9, 341.

675 with other had levels 19 non-prostatic conditions, prostatic them and of above 100 above 3 units per ml., only 5 levels noted the same WRAY 13 5 units. By method, in of ml. 43 out 73 above 3 units per 100 patients with but in 1 out of 427 with only prostatic carcinoma, Various explanations have been other conditions. suggested for the normal levels often found in proved carcinoma of the prostate. It is possible that " barriers exist in the normal prostate gland that prevent the " io escape of acid phosphatase into the circulation and that invasion or metastasis is necessary before the 11 Production of the enzyme may serum levels rise.2 cease in anaplastic growths 2 ; and previously raised blood-levels may be temporarily much reduced during intercurrent fever.8 An acid-phosphatase inhibitor has been demonstrated in some cases.14 Whatever the reasons, normal serum-acid-phosphatase levels cannot be taken as evidence against a diagnosis of carcinoma of the prostate. But levels between 3 and5 units per 100 ml., by the formaldehyde method, should be regarded as suspicious and levels above 5 units as strong evidence for such a diagnosis. Urinary retention,13 prostatic massage,13 liver disease, and Paget’s disease of bone 4 11 may all, how’’ ever, give rise to false-positive results. The effect of oestrogen therapy on prostatic carcinoma with high initial serum-acid-phosphatase levels can be judged by following the return of these levels to

5 units.

In contrast, of 101

patients

or

"

normal.29 A phosphatase active at an alkaline reaction is related to bone production.16s Raised serum-alkalinephosphatase levels are found in many bone7 diseases, including secondary malignant disease,1 and in obstructive jaundice.18 Workers who have studied alkaline as well as acid phosphatase in serum in relation to carcinoma of the prostate have generally found that alkaline phosphatase is sometimes increased but it is not of much clinical value.8 WRAY, however, lately recorded characteristic patterns of behaviour of plasma-alkaline-phosphatase levels after oestrogen treatment of prostatic carcinoma.13 When the plasma-

alkaline-phosphatase value was initially normal, a rise started immediately after stilboestrol therapy began. After reaching a peak, the value fell to normal When the alkaline phosphatase was more slowly.

,

much raised at the start there was an initial fall coinciding with the start of stilboestrol, but after a few days it began to rise again and reached a peak above its initial value within thirty to forty days. Thereafter there was a gradual fall, as in patients with initially normal- alkaline-phosphatase levels. WRAY found these changes helpful in confirming the diagnosis of metastasising prostatic carcinoma, in indicating the presence of unsuspected secondary deposits, and injudging the effects of treatment. In at least 1 patient, failure of the expected pattern to appear was followed by the discovery that the primary tumour was bronchial not prostatic. Such findings, if confirmed, will provide a useful supplement to acid-phosphatase studies in the diagnosis and management of carcinoma of the prostate. 14.

15. 16. 17. 18.

Hudson, P. Progress Report, Department of Urology, University, 1954. Hock, E., Tessier, R. N. J. Urol. 1949, 62, 488. Robison, R. Biochem. J. 1923, 17, 286. King, E. J., Delory, G. E. Postgrad. med. J. 1948, 24, Sherlock, S. J. Path. Bact. 1946, 58, 523.

Columbia

299.

University Apartheid WHEN the United States Supreme Court decided in 1954 that, for white and coloured students, separate educational facilities are inherently unequal," it was making an observation as relevant to South Africa as to the United States. In the same way that the Jim Crow colleges and schools acquired an inferior status and a reputation for poor training, indifferent staff, and inadequate funds, South African non-European institutions have been handicapped in comparison with those for whites ; and neither schools nor colleges " for non-Europeans only " have reached anything like European levels. At the " mixed universities of Cape Town and Witwatersrand European and non-European students have been "

"

given opportunities that were as nearly equal as seemed possible. For medical graduates, the rewards of qualifying may be less (African, Coloured, and European interns, for instance, working at the same hospital, are paid at different rates), but the degrees of all students are nevertheless equal. These mixed universities have been a healthy feature of South African life, for they have provided one of the few social meeting-places for young men and women of different races. A spirit of racial cooperation has distinguished these students from their contemporaries, white and black, of segregated universities in the country, and the main opposition to segregated university education comes from these universities and their graduates. When, in 1951,1 the Durban medical school was established as part of the Natal University, it represented to some extent a compromise between mixed and segregated institutions. Natal University had students of all races, but conducted parallel classes for Europeans and non-Europeans, thus accepting internal segregation. In the hope of those who had worked for its establishment, the Durban medical school was to be primarily non-European," but not exclusively so. The Union government, however, offered to take full financial responsibility for the school, and it made the condition (reluctantly accepted by Natal University) that only non-Europeans were to be admitted to the school, except when special permission was granted by the minister of education. Moreover, to further the aim of segregation, bursaryloans were offered to medical students on the condition that bursars undertook to confine their practice to non-Europeans and to work only in areas approved by the South African government. One of the government’s objects in developing the Durban medical school was to enable it to remove non-European medical students from the mixed universities and offer them alternative places in Durban. The minister of education specifically promised that the Durban school, though segregated, would be equal to the white institutions ; and this makes developments at Durban of crucial interest to multiracial societies everywhere : it provides one more experiment in segregated education. Men and women of distinction were attracted to the posts at the Durban school, partly because of its association with the university, partly by the promise of stimulating teaching and research in a non-European All were completely determined that no school. "

1.

Report on the Government’s intended action to remove the Durban Faculty of Medicine from the University of Natal. Medical School, March 4. 1957.