665

sponse which is consistent, therefore, with the

known changes induced in the kinin system bychanges in salt balance. Further, the additionalvasodepressor property of converting-enzyme inhi-bition is abolished by nephrectomy, indicating thatthe kidneys have an essential part in this mechan-ism for blood-pressure reduction.

There are thus two clinical situations to beadded to the list of conditions in which the kinin

system is important=hypotensive reactions to plas-ma-protein preparations, and blood-pressure lower-ing with converting-enzyme inhibitor. In additionthere is a possibility that new observations have un-covered an important renal vasodepressor system.If so, some questions arise. Why, for instance, isthere no severe tachycardia and flushing with

bradykinin potentiation? How are the inflamma-tory and vasodepressor effects of the kinin systemseparately controlled? How far do the different kal-likreins from different organs have different phy-siological functions, and how far does the kinin sys-tem act as a local mediator in renal, glandular, orvascular tissue? Another possible link between therenin-angiotensin and kinin systems has beenrevealed by experiments in Glasgow,30 Rotier-

dam,31 and New York32 suggesting that kallikreincan activate inactive renin. These provide either aclue or a further complexity for workers in thispuzzling sphere. There may yet be surprises.

Research in Systemic LupusErythematosus

FOUR years ago, the aetiology of systemic lupuserythematosus and, by optimistic analogy, of rheu-matoid arthritis was apparently within reach.

C-type viral particles, known to play a role in thedisease of New Zealand mice,l 2 had been impli-cated in a lupus-like disease of dogs. Cell-free

spleen filtrates from these animals, when inocu-lated into mice, produced serological abnormalitiessuggestive of S.L.E. in some recipients and lym-phoid tumours in others. One of these neoplasms,in turn, produced a monoclonal antibody againstdouble-stranded D.N.A. With a purified antiserumagainst the C-type particle, membrane fluorescencewas seen on the lymphocytes of five out of six S.L.E.patients. Then STRAND and AUGUST3 found bycompetitive radioimmunoassay C-type proteins inthree S.L.E. tissues; and by immunofluorescence

30. Leckie, B. Lancet, July 22, 1978, p. 217.31. Derkx, F. H M., Tan-Tjiong, H L., Schalekamp, M. A D. H. ibid. p. 218.32. Sealey, J. E., Atlas, S. A., Laragh, J. H., Oza, N. B., Ryan, J. W. Nature,

1978, 275, 144.1 Lewis, R M , Tannenberg, W., Smith, C., Schwartz, R. S. Nature, 1974,

252, 782. Pincus, T. in Modern Topics in Rheumatology (edited by G R. V. Hughes);

p 107 19763 Strand, M, August, J T J. Virol. 1974, 14, 1584.

with antisera to C-type viruses MELLORS andMELLORS demonstrated C-type antigens in renal-biopsy material from S.L.E. patients.4 Another

study5 suggested that s.L.E. leucocytes containedboth C-type reverse transcriptase and D.N.A. com-plementary to measles R.N.A., pointing to possiblecooperation between measles and C-type viruses inthe production of s.L.E.

Despite these striking findings, the momentumof the C-type virus bandwagon has slowed duringthe past two years. The data implicating coopera-tion between measles and C-type virus have notbeen confirmed,6 C-type antigens have been foundin non-s.L.E. tissues,7 and careful isolation studiesin S.L.E.8 have not yielded viruses. In the spring of1977, a group of virologists, geneticists, immunolo-gists, and rheumatologists met in Arizona to dis-cuss new directions for research in systemic lupuserythematosus. The proceedings, under the editor-ship of Dr ROBERT WINCHESTER, have just beenpublished and they provide a comprehensive reviewof existing knowledge and of techniques for investi-gating the various diseases where infective, im-munological, and genetic factors seem to interact.Isolation procedures for R.N.A. viruses and virus/lymphocyte interactions are discussed in detail.Certain viruses may depress T-lymphocyte helperand effector activities, and work is presented,employing C-type Moloney leuksemia virus as theinfective agent, supporting the hypothesis that in-fection of certain clones of thymic cells with auto-reactive potential fixes this autoreactivity. Amongthe target cells for this autoreactive cytotoxicity areperipheral lymphoid cells with antiviral activity.10Indirect evidence for the presence of viral infectionin s.L.E. also comes from the finding of cold-react-ing lymphocytotoxic antibodies in 80% of S.L.E.patients as well as in 40%-60% of their symptom-less household contacts. 11 These antibodies are

almost certainly a heterogeneous group, possiblyincluding a group directed against viral antigens oncells of normal individuals, as well as true anti-bodies expressed through a defect in immune toler-ance. That they may play a secondary role in theclinical expression of S.L.E. is suggested by thecross-reactivity seen against placental-trophoblastantigens in S.L.E. patients with spontaneous abor-tionsl2 and against brain in patients with neuropsy-

4. Mellors, R.C., Mellors, J.W. Arthritrs Rheum 1978, 21, s 68.5. Alekberova, Z. S., Parfanovich, M. I., Nassonova, V. A., Zhdanov, V. M.

Archs Virol. 1975, 47, 1096. Haase, A. T., Stowring, L., Ventura, P., et al in Microbiology (edited by D.

Schlessinger); p. 478 Washington (Am Soc. Microbiol), 19277. Phillips, P. E. Arthritis Rheum 1978, 21, s 76.8 Phillips, P. E., Hargrave, R , Stewart, E, Sarkar, N H Ann rheum Dis

1976, 35, 422.9 Winchester, R Arthritis Rheum. 1978, 21, no 5 (suppl)

10 Black, P H. and Hirsch, M. S ibid p s 17.11 Messner, R P, Delloratius, R. J ibid p. s 167.12. Bresnihan, B., Grigor, R. R , Oliver, M., Lewkonia, R, Hughes, G. R. V.,

et al Lancet, 1977, ii, 1205

666

chiatric manifestations. 13 14 Whether the T lym-phocytopenia and defective suppressor T-cellfunction seen in S.L.E. is related’to viral destructionof T cells, antilymphocyte antibodies, or tissue

sequestration is uncertain.Indications of a genetic component in the setiol-

ogy of S.L.E. have come from family and twin stu-dies and from the growing number of cases associ-ated with genetic complement deficiencies.16 HLAstudies have shown no clear association withknown A, B, or C loci, and HLA-D studies in s.L.E.have been hampered by technical problems. How-ever, data reported by STASTNy17 suggest a statisti-cally significant increase in the antigen Ia4. Thisapparently exclusive association with a D locus isof interest in that the HLA-D complex is thehuman histocompatibility-linked immune-responseregion. One attractive postulate therefore is thatthe immunological deficit seen in S.L.E. may be dueto a lack of immune-response (or to the presence ofimmune-suppressor) genes, resulting in the persist-ence of an infectious agent or its products. Whilethere are almost certainly many xtiological factorsin the disease, the careful collaborative data pre-sented in this report firmly places a C-type virus atthe head of the list of putative infective agents trig-gering the clinical syndrome of s.L.E.

HIGH HOPES AT ALMA-ATA

ON Sept. 6 in Alma-Ata, the capital of the SovietRepublic of Kazakstan, 600 representatives of 150member states of the World Health Organisation as-

sembled so that they might discuss what could be achievedfor the 2000 million people who have no access to ade-quate health care. The Government of the U.S.S.R. washost to this company, whose meeting was sponsoredjointly by UNICEF and W.H.O. The prescription to bedebated was a new approach to primary health care, bymeans of which to attain W.H.O.’s aim of health for all

by the year 2000. The meeting ended with a strong senseof a landmark achieved, though it had begun in doubt,because of the two seemingly opposed attitudes whichhad been apparent in the three years of preliminary dis-cussions preceding the event. The U.S.S.R. and otherSocialist states had taken the view that only doctors andfull health professionals could deliver effective healthcare (there are now 685 000 Soviet doctors available fortheir population of 265 million-an achievement whichmay have influenced the judgment). Yet, the other argu-ment ran, the condition of the underserved developing

13. Bluestein, H. G., Zvaifler, N. J. J. clin Invest. 1976, 57, 509.14. Bresnihan, B., Oliver, M., Grigor, R. R., Hughes, G. R. V. Clin. exp. Im

mun. 1977, 30, 333.15. Christian, C L. Arthritis Rheum. 1978, 21, s 130.16. Agnello, V. ibid p s 146.17. Stastny, P. ibid. p. s 139.

countries left little doubt that many large communitieswould fail to receive adequate health care in the nearfuture unless other kinds of health workers could be

rapidly produced within those communities; and suchsystems must strive to apply a more practical technologythan the one which was now straining the resources ofthe highly industrialised countries. The immediate needwas for simple but effective curative services, preventivemeasures, and, through community education, the en-couragement of life-styles which might improve thehealth of individuals, families, and communities.

In the event there was a striking consensus. All agreedthat a country-by-country approach was needed: no oneorganisational pattern would do for all. Each must de-velop its strategy to meet its own hazards-a strategybased on sound epidemiological analysis and relevant tothe country’s state of development. Each must cut thecloth according to the purse, but the garment must beeffective and accessible to all the population.The conference issued a declaration-a short docu-

ment (presently to be published by W.H.O.) which couldserve as a guide for some years to come. It might helpto stimulate the national political commitment necessaryfor the allocation of sufficient resources to the healthcare of whole communities. The present health of morethan half the population of the world was seen, in thedeclaration, as morally and politically unacceptable, aswas the unequal distribution of health resources

between and within countries. The declaration recog-nised that health was not achieved solely by medicalefforts and called for a many-sided undertaking by allsections of health workers and of governments. The wayto a health revolution lay, as has so often been urgedbefore, through better nutrition, safe water, basic sani-tation, immunisation against major infectious diseases,accessible treatment (including the provision of essentialdrugs), and community, ’family, and individual educa-tion and participation.

The document is important enough, short enough,and sufficiently comprehensible (by international stan-dards) to merit examination by all members of thehealth professions, especially by doctors. It containsmuch that is relevant to the developed countries, whooften seem slow to respond to avoidable hazards. Fromthe Alma-Ata recommendations may flow coordinatedactions which could help to put into the past such de-plorable statistics as the forecast that 152 millionchildren under the age of five will die in 1979-15 mil-lion of them in the developing world.

IMPACT OF A SUICIDE INQUEST

IN several papers, Barraclough and others’-5 arguefor restrictions on the reporting of coroners’ inquestswhere there is a verdict of suicide. They supply threesorts of data-interviews with relatives, analysis of

newspaper reports, and frequency of male suicides aftersuch reports. They interviewed 31 out of 34 surviving

1. Barraclough, B. M., Shepherd, D. M. Br. J. Psychiat. 1976, 129, 109.2. Barraclough, B. M., Shepherd, D. M. ibid. 1977, 131, 400.3. Barraclough, B. M., Shepherd, D. M., Jennings, C. ibid. p. 528.4. Shepherd, D. M., Barraclough, B. M. ibid. 1978, 132, 283.5. Shepherd, D. M., Barraclough, B. M. Br. med. J. 1974, ii, 600.