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iimcult to demonstrate because of artefacts producedduring fixation of tissue for microscopy, but electron-microscope examination of brain tissue made arti-ficially oedematous by ischaemia or metabolic poisonsproves this sequence of events. 21,22 The brain is, ofcourse, particularly vulnerable because of its positionwithin the rigid skull.An overall shift of sodium and water into cells will

not by itself produce plasma hyponatraemia; FLEARand SINGH 10 promote the view that a widespread andsudden increase in the membrane permeability ofsick cells allows intracellular solutes to leak out intothe extracellular compartment, together with potas-sium ions. This offsets the osmotic effect of an influxof sodium ions, so that there is little net diffusion ofwater into cells. This increase in permeability maybe a primary event in the development of the sick-cell syndrome, but perhaps a more logical suggestionis that the increase in permeability is secondary tothe cell swelling which follows inhibition of the

A.T.p.ase-dependent ion-exchange pump.Even if the exact mechanism is not clear, the con-

cept of the sick cell is useful in the management of

patients with hyponatraemia. Firstly, it reinforcesthe view that hyponatrxmia is a side-effect of under-lying illness, which can be expected to resolve

spontaneously if the patient responds to treatment ofthat illness. Therefore there is usually no need fordirect correction of hyponatrxmia, for example withhypertonic saline; such treatment may in any eventbe dangerous in conditions such as cardiac or hepaticfailure. Secondly, if the concept of the sick cell is

valid, measures aimed at improving cell-membranetransport should be helpful. Since tissue hypoxiamay lie at the root of at least some cases of the sick-cell syndrome, general measures to improve tissueperfusion and oxygenation must be given priority;however, from the work Of ZIERLER and RABINOWITZ 23and CREESE 24 it is clear that insulin will stimulateion exchange in cell membranes independently ofglucose uptake. The regimen of glucose, potassium,and insulin, first devised by SODI-PALLAREs and hiscolleagues 25 and more lately evaluated by ALLISON’Sgroup,26,27 has been used with convincing success inseriously burned patients and with some success inpatients with congestive cardiac failure. The role ofsteroids in hyponatrasmia has not been preciselydefined, though the often dramatic effect of dexa-methasone in relieving cerebral oedema may be partlydue to increased ion exchange accompanying a rise21. Chiang, J., Kowada, M., Ames, A., Wright, R. L., Majno, B. Am.

J. Path. 1968, 52, 455.22. Baethmann, A., Van Harrevald, A. J. Neuropath. exp. Neurol.

1973, 32, 408.23. Zierler, K. L., Rabinowitz, D. J. clin. Invest. 1964, 43, 950.24. Creese, R. J. Physiol., Lond. 1968, 197, 255.25. Sodi-Pallares, D., Testelli, M. R., Fishleder, B. L., Bisteni, A.,

Medrano, G. A., Friedland, C., De Micheli, A. Am. J. Cardiol.1962, 9, 166.

26. Allison, S. P., Morley, C. J., Burns-Cox, C. J. Br. med. J. 1972,iii, 675.

27. Hinton, P., Allison, S. P., Littlejohn, S., Lloyd, J. Lancet, 1973, ii,218.

in intracellular 3’,5’-cyclic A.M.P. 28 Further work isneeded on the effect of measures designed to improvemembrane transport in patients suspected of havingthe sick-cell syndrome: the results will be of boththeoretical and practical importance.

ULSTER CATHARSIS

THE ability of psychiatrists to perceive good newsin even the gloomiest of situations is well illustratedby studies of the incidence and prevalence of

psychiatric disorders during times of war and civildisturbance. During the 1939-45 war admission-ratesfell and severe neurosis was rare except in individualswho were neurotic before the war started 29, 30 Morerecent studies of psychiatric disorders amongst combattroops in Vietnam, 31 showing a low incidence of

depressive illness, lend support to Kendell’s hypothesisthat depression may be due to inhibition of aggressiveresponses to frustration.32 2 The disturbances inNorthern Ireland have provided a contemporary modelof civil commotion and unhibited aggressive responseswherein some of these issues can be explored further,and an inverse relationship between the incidence ofdepressive illness and opportunities to externalise

aggression has been demonstrated.33 Areas outside themain trouble-spots have shown an increase in theincidence of depression, whereas riot areas havewitnessed a fall in the rates of both depression andsuicide. The price paid for such changes-in termsof murder, arson, and torture-has of course been ahideous one. And now evidence has been presentedin an education journal 34 that the price currently beingpaid for the apparent improvement in adult mentalhealth in Ulster may not be the final one. In the viewof many educationists and some psychiatrists, seriousdeterioration in the psychological health of tomorrow’sadult generation seems an inevitable outcome of today’sviolence. Lyons, reporting an analysis of the essaysof Catholic and Protestant schoolchildren, declares" there is little doubt that they are conditioned tohate the other side during their formative years " andargues that long before they are mature enough tounderstand the true significance of what is happeningthey have already absorbed the historical stereotypesaccepted by many of their parents.34The troubles in Ulster are almost five years old,

and children who were infants at their onset have nowhad their minds moulded by bigotry and fear duringthe most formative years of their lives. Small wonderthat gangs of children strut and wheel like soldiers onthe march and form rival sectarian gangs which fightnot only each other but also the soldiers and the

police. Small wonder also that some of those who

fought children’s fights in children’s gangs now aremembers of more sinister adult organisations. How-

ever, if one excludes antisocial behaviour, relatively28. Rooney, P. J., Lee, P., Brookes, P., Carson Dick, W. Curr. med.

Res. Opin. 1973, 1, 501.29. Brown, E. Hansard, June 30, 1942.30. Lewis, A. Lancet, 1941, ii, 175.31. Duy San, N. in The Psychology and Physiology of Stress (edited

by P. G. Bourne); chap. 3, p. 45. New York, 1969.32. Kendell, R. E. Archs gen. Psychiat. 1970, 22, 308.33. Lyons, H. A. Br. med. J. 1972, i, 342.34. Lyons, H. A. Northern Teacher, Winter, 1973.

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few of the children seem disturbed. Drug-taking hasdropped in troubled areas; anxiety symptoms are

rare, and they tend to affect children whose parentshave had the same symptoms either previously orconcurrently. It would be naive, Lyons observes, toexpect that teenagers and younger children, used bymilitant organisations during the troubles, will becontent to satisfy their present and future needs amidplay-centres, football pitches, and sports fields.The recurrent theme in this issue of The Northern

Teacher is the problem of exploiting, in a productiveand constructive fashion, the immense emotionalforces which have been liberated among the youngpeople of the province by the current disturbances.Thought is also given to how the divisions in thecommunity might be healed. Fraser has argued that" total integration of children from primary-school-ageupwards would be the most potent single factor inbreaking down community barriers and in restoringlong-term peace". 35 Reading the journal, with itsalmost unbearably moving accounts from pupils of themurder of fathers and the burning of homes, one isstruck by the prediction that, when peace comes, theincidence of mental illness, delinquency, and minorcrime will rise again, and that not merely parents andpoliticians but also educationists, probation officers,social workers, and psychiatrists will be required tohelp heal the wounds.

FAMILY PLANNING IN THE THIRD WORLD

THOSE who supervised the control of infectiousdisease in developing countries have been less energeticin tackling one of its consequences-a massive increasein population. The price of this delay is already beingseen in a standstill or even relapse in per-caputeconomic growth and in massive underemployment andmalnutrition; and indigenous support for the economiesof the third world is falling on a working populationwhich constitutes an increasingly small proportionof the total. The interdependence of health, economicgrowth, population, education, and resources was

well illustrated in a lecture given by Dr F. T. Sai atthe London School of Hygiene and Tropical Medicineon Feb. 21. Dr Sai argued that those setting nationaltargets must take all these factors into account in their

plans-a policy which, had it been adopted by thedeveloped world a generation ago, might have pre-vented a lot of the hardship being suffered today.The developed countries put restraints on some

family-planning methods, and Dr Sai believes thatsuch policies have made the wide availability of certaincontraceptive methods in developing countries a

difficult objective. He claimed that Britain and theUnited States, in restricting the pill to prescriptiononly, had given a wrong lead--or, as he put it, therehad been a " freak echo " taken up by leaders in thedeveloping world. Whether he was really advocatingthe free availability of oral contraceptives in allcountries is not clear, but the more we learn abouthormonal contraceptives the less likely it looks thatan over-the-counter policy should prevail.

35. Fraser, R. N. Wld Med. June, 1972.

In Britain the introduction of family planningwithin the N.H.S. has had to be delayed by severalmonths because of lack of agreement about payment;in the Republic of Ireland and France there are

barriers just as strong as the cultural ones to

be surmounted in Africa; in New York services areso difficult to run that they are being put into thehands of anyone who can pass the course. Perhaps thesolution for the Governments of the third world isnot to allow themselves to be led but to come to theirown decisions in the full recognition that a few

imperfections in the service they provide may be aprice well worth paying. Speakers at a conferenceheld in Sri Lanka in January (see p. 370) seemedwilling to keep an open mind on the question ofmedical supervision of family planning. Medicalknowledge should certainly be universal; but it neednot be applied with unthinking uniformity.

ICRF 159

ALTHOUGH the neoplastic cells that comprise a

malignant tumour have been examined from almostevery conceivable angle, the important fibrovascularstromal elements which provide the means for bothnutrition and dissemination have received less atten-tion. The morphologically abnormal blood-vesselsthat occur in or near malignant tumours are familiarenough 1; and much work has been done on morefunctional aspects of tumour vasculature. Attentionhas been drawn to the kinetics of endothelial cells,2,3and to various abnormal responses to vasoactive

agents of blood-vessels in tumours.4-6 Tumourvasculature may well comprise a weak link which canbe exploited therapeutically-to control the growthof the primary lesion and perhaps also the initial

phases of haematogenous dissemination. There isevidence that ICRF 159, the bis diketopiperazinecompound (±)1,2 bis (3,5 dioxopiperazinyl) propane,may act at this point.The initial discovery of ICRF 159 seems to have

arisen from the misconceived generalisation that theactivity of antitumour drugs depends on their chelatingproperties. Admittedly, the potent chelating agentedetic acid (E.D.T.A.) has no antitumour activity;but E.D.T.A. is a highly polar molecule, and a group ofless polar chelating agents was accordingly studied.’Some were active against a number of experimentaltumours, but it became clear that one of the com-

pounds, ICRF 159, exerted remarkable effects againstmetastases. With the murine Lewis tumour, variousdose schedules of ICRF 159 (injected intraperi-toneally) prevented or greatly reduced the develop-ment of pulmonary deposits even though growth ofthe "

primary " transplant in the flank was littleaffected. 8 Subsequent experiments showed that

1. Willis, R. A. Spread of Tumours in the Human Body. London, 19732. Tannock, I. F. Cancer Res. 1970, 30, 2470.3. Tannock, I. F., Hayashi, S. ibid. 1972, 32, 77.4. Cater, D. B., Adair, H. M., Grove, C. A. Br. J. Cancer, 1960.

20, 504.5. Cater, D. B., Taylor, C. R. ibid. p. 517.6. Underwood, J. C. E., Carr, I. J. Path. 1972, 107, 157. 1965

7. Crieghton, A. M., Hellmann, K., Whitecross, S. Nature, 1960222, 384.

8. Hellmann, K., Burrage, K. ibid. 1969, 224, 273.