sponse which is consistent, therefore, with the known changes induced in the kinin system by changes in salt balance. Further, the additional vasodepressor property of converting-enzyme inhibition is abolished by nephrectomy, indicating that the kidneys have an essential part in this mechanism for blood-pressure reduction.
thus two clinical situations to be the list of conditions in which the kinin are
added to system is important=hypotensive reactions
plasma-protein preparations, blood-pressure lowering with converting-enzyme inhibitor. In addition there is a possibility that new observations have uncovered an important renal vasodepressor system. If so, some questions arise. Why, for instance, is there no severe tachycardia and flushing with bradykinin potentiation? How are the inflammatory and vasodepressor effects of the kinin system separately controlled? How far do the different kallikreins from different organs have different physiological functions, and how far does the kinin system act as a local mediator in renal, glandular, or vascular tissue? Another possible link between the renin-angiotensin and kinin systems has been revealed by experiments in Glasgow,30 Rotierdam,31and New York32 suggesting that kallikrein can activate inactive renin. These provide either a clue or a further complexity for workers in this puzzling sphere. There may yet be surprises. to
Systemic Lupus Erythematosus
FOUR years ago, the
aetiology of systemic lupus erythematosus and, by optimistic analogy, of rheumatoid arthritis was apparently within reach. C-type viral particles, known to play a role in the disease of New Zealand mice,l2 had been implicated in a lupus-like disease of dogs. Cell-free spleen filtrates from these animals, when inoculated into mice, produced serological abnormalities suggestive of S.L.E. in some recipients and lymphoid tumours in others. One of these neoplasms, in turn, produced a monoclonal antibody against double-stranded D.N.A. With a purified antiserum against the C-type particle, membrane fluorescence was seen on the lymphocytes of five out of six S.L.E. patients. Then STRAND and AUGUST3 found by competitive radioimmunoassay C-type proteins in three 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, 78 2. Pincus, T. in Modern p 107 1976 3 Strand, M, August,J
Rheumatology (edited by
T J. Virol. 1974, 14, 1584.
G R. V.
with antisera to C-type viruses MELLORS and MELLORS demonstrated C-type antigens in renalbiopsy material from S.L.E. patients.4 Another study5 suggested that s.L.E. leucocytes contained both C-type reverse transcriptase and D.N.A. complementary to measles R.N.A., pointing to possible cooperation between measles and C-type viruses in the production of s.L.E. Despite these striking findings, the momentum of the C-type virus bandwagon has slowed during the past two years. The data implicating cooperation between measles and C-type virus have not been confirmed,6 C-type antigens have been found in non-s.L.E. tissues,7 and careful isolation studies in S.L.E.8 have not yielded viruses. In the spring of 1977, a group of virologists, geneticists, immunologists, and rheumatologists met in Arizona to discuss new directions for research in systemic lupus erythematosus. The proceedings, under the editorship of Dr ROBERT WINCHESTER, have just been published and they provide a comprehensive review of existing knowledge and of techniques for investigating the various diseases where infective, immunological, 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 helper and effector activities, and work is presented, employing C-type Moloney leuksemia virus as the infective agent, supporting the hypothesis that infection of certain clones of thymic cells with autoreactive potential fixes this autoreactivity. Among the target cells for this autoreactive cytotoxicity are peripheral lymphoid cells with antiviral activity.10 Indirect evidence for the presence of viral infection in s.L.E. also comes from the finding of cold-reacting lymphocytotoxic antibodies in 80% of S.L.E. patients as well as in 40%-60% of their symptomless household contacts. 11 These antibodies are almost certainly a heterogeneous group, possibly including a group directed against viral antigens on cells of normal individuals, as well as true antibodies expressed through a defect in immune tolerance. That they may play a secondary role in the clinical expression of S.L.E. is suggested by the
cross-reactivity seen against placental-trophoblast antigens in S.L.E. patients with spontaneous abortionsl2 and against brain in patients with neuropsy4. 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, 109 6. Haase, A. T., Stowring, L., Ventura, P., et al in Microbiology (edited by D.
Schlessinger); p. 478 Washington (Am Soc. Microbiol), 1927 7. 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
chiatric manifestations. 13 14 Whether the T lymphocytopenia and defective suppressor T-cell function seen in S.L.E. is related’to viral destruction of T cells, antilymphocyte antibodies, or tissue
sequestration is uncertain. Indications of a genetic component in the setiology of S.L.E. have come from family and twin studies and from the growing number of cases associated with genetic complement deficiencies.16 HLA
studies have shown no clear association with known A, B, or C loci, and HLA-D studies in s.L.E. have been hampered by technical problems. However, data reported by STASTNy17 suggest a statistically significant increase in the antigen Ia4. This apparently exclusive association with a D locus is of interest in that the HLA-D complex is the human histocompatibility-linked immune-response region. One attractive postulate therefore is that the immunological deficit seen in S.L.E. may be due to a lack of immune-response (or to the presence of immune-suppressor) genes, resulting in the persistence of an infectious agent or its products. While there are almost certainly many xtiological factors in the disease, the careful collaborative data presented in this report firmly places a C-type virus at the head of the list of putative infective agents triggering the clinical syndrome of s.L.E.
HIGH HOPES AT ALMA-ATA
Sept. 6 in Alma-Ata, the capital of the Soviet Republic of Kazakstan, 600 representatives of 150 member states of the World Health Organisation assembled so that they might discuss what could be achieved for the 2000 million people who have no access to adeON
quate health care. The Government of the U.S.S.R. was host to this company, whose meeting was sponsored jointly by UNICEF and W.H.O. The prescription to be debated was a new approach to primary health care, by means of which to attain W.H.O.’s aim of health for all by the year 2000. The meeting ended with a strong sense of a landmark achieved, though it had begun in doubt, because of the two seemingly opposed attitudes which had been apparent in the three years of preliminary discussions preceding the event. The U.S.S.R. and other Socialist states had taken the view that only doctors and full health professionals could deliver effective health care (there are now 685 000 Soviet doctors available for their population of 265 million-an achievement which may have influenced the judgment). Yet, the other argument 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
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. mun.
countries left little doubt that many large communities would fail to receive adequate health care in the near future unless other kinds of health workers could be rapidly produced within those communities; and such systems must strive to apply a more practical technology than the one which was now straining the resources of the highly industrialised countries. The immediate need was for simple but effective curative services, preventive measures, and, through community education, the encouragement of life-styles which might improve the health of individuals, families, and communities. In the event there was a striking consensus. All agreed that a country-by-country approach was needed: no one organisational pattern would do for all. Each must develop its strategy to meet its own hazards-a strategy based on sound epidemiological analysis and relevant to the country’s state of development. Each must cut the cloth according to the purse, but the garment must be effective and accessible to all the population. The conference issued a declaration-a short document (presently to be published by W.H.O.) which could serve as a guide for some years to come. It might help to stimulate the national political commitment necessary for the allocation of sufficient resources to the health care of whole communities. The present health of more than half the population of the world was seen, in the declaration, as morally and politically unacceptable, as was the unequal distribution of health resources between and within countries. The declaration recognised that health was not achieved solely by medical efforts and called for a many-sided undertaking by all sections of health workers and of governments. The way to a health revolution lay, as has so often been urged before, through better nutrition, safe water, basic sanitation, immunisation against major infectious diseases, accessible treatment (including the provision of essential drugs), and community,’family, and individual education and participation. The document is important enough, short enough, and sufficiently comprehensible (by international standards) to merit examination by all members of the health professions, especially by doctors. It contains much that is relevant to the developed countries, who often seem slow to respond to avoidable hazards. From the Alma-Ata recommendations may flow coordinated actions which could help to put into the past such deplorable statistics as the forecast that 152million children under the age of five will die in 1979-15 million of them in the developing world.
IMPACT OF A SUICIDE INQUEST IN several papers, Barraclough and others’-5 argue for restrictions on the reporting of coroners’ inquests where there is a verdict of suicide. They supply three sorts of data-interviews with relatives, analysis of newspaper reports, and frequency of male suicides after such reports. They interviewed 31 out of 34 surviving 1. 2. 3. 4. 5.
Barraclough, B. M., Shepherd, D. M. Br. J. Psychiat. 1976, 129, 109. Barraclough, B. M., Shepherd, D. M. ibid. 1977, 131, 400. Barraclough, B. M., Shepherd, D. M., Jennings, C. ibid. p. 528. Shepherd, D. M., Barraclough, B. M. ibid. 1978, 132, 283. Shepherd, D. M., Barraclough, B. M. Br. med. J. 1974, ii, 600.