277

often responds well to intensive intravenous fluids, correctionof electrolytes, steroids, and withdrawal of antibiotics.

We thank Mr A. W. Hargreaves for assistance in publishing thiscase.

Salford Royal Hospital,Manchester M60 9EP

J. A. C. THORPEA. NYSENBAUM

ACTIVE THERAPEUTIC MOIETY OFSULPHASALAZINE

SiR,-The efficacy of sulphasalazine in ulcerative colitis hasbeen established in several well-controlled trials. After inges-tion most of the drug reaches the colon where it is completelysplit by bacteria into sulphapyridine and 5-aminosalicylic acid(5-A.S.A.). Sulphasalazine is most effective at the site of break-down. This suggests that a metabolite rather than the parentcompound is responsible for the drug’s activity.

, To determine the therapeutically active moiety of sulphasa-lazine, suppositories of sulphapyridine (300 mg), 5-A.S.A. (200mg), or placebo were given to patients with idiopathic proc-titis. We did not give sulphasalazine suppositories because thedrug is split into sulphapyridine and 5-A.S.A. in the rectumalso.The study was double blind, and the patients were allotted

at random to one of the three types of suppository. The pa-tients took two suppositories per day for four weeks. Sigmoi-doscopy was done before and after the trial. The preliminaryresults, after inclusion of thirty patients in the trial, are as fol-lows (remission being defined as complete disappearance ofclinical symptoms and a normal rectal mucosa at sigmoid-oscopy) :

These results accord with those of Azad Khan et al.l

Although the number of patients is small, our results supportthe view that 5-A.S.A. is the therapeutically active moiety ofsulphasalazine.Division of Gastroenterology,Department of Medicine,and Department of Pharmacy,

St Radboud Hospital,University of Nijmegen,Nijmegen, Netherlands,and Department of Statistical Consultation,

University of Nijmegen

P. A. M. VAN HEES

J. H. M. VAN TONGERENJ. H. BAKKERH. J. J. VAN LIER

INDOMETHACIN AND &bgr;-BLOCKERS INHYPERTENSION

SiR,—Durao et al. showed that indomethacin modified theeffect of p-blockers on arterial pressure in hypertension. Wehave found a a reactive increase in prostaglandin activity in 13patients with essential hypertension all with normal renalfunction. 6 volunteers were controls. After 3 days on indo-methacin (150 mg/day), the mean arterial pressure in thehypertensive group increased from a basal mean value of118i9 mm Hg to 131±8 mm Hg. Weight increased from amean basal value of 72± 14 kg to 74+14 kg. The glomerularfiltrate and the renal plasma-flow, measured as the creatinineclearance and p-aminohippuric acid clearance, decreased from95+20 and 612±120 ml/min, respectively, to 78±24 and499±140 ml/min, respectively. The plasma-renin activity andplasma-aldosterone decreased from 12+10 ng/ml/3h and 14±6 6ng/dl respectively to 4±3 ng/ml/3h and 8-9±6 ng/dl respec-

1. Azad Khan, A. K., Pins, J., Truelove, S. C. Lancet, 1977, ii, 892.2. Durão, V., Prata, M. M., Gonçalves, L. M. P. Lancet, 1977, ii, 1005.3. Barrientos, A., Alcazar, J. M., Ruilope, L., Jarillo, D., Rodicio, J. L.

Abstracts of meeting of Spanish Society of Nephrology. San Sebastian,1977, p. 111.

tively. All of these changes were statistically significant. Therewere no significant changes in the control group.

Indomethacin may thus interfere with p-blockers by its

hypertensive activity rather than by modifying the synthesis ofprostaglandins upon which the p-blockers depend.

A. BARRIENTOSV. ALCAZARL. RUILOPED. JARILLOJ. L. RODICIO

Servicio de Nefrologia,Cuidad Sanitaria de la Seguridad Social

1° de Octubre,Madrid, Spain

PLATELET AGGREGATION INDUCED BY SWINEINFLUENZA VACCINE

SIR,-Rivard and Potier propose that platelet aggregatesinduced in some elderly people vaccinated with swine influenzavaccine in the United States may have caused some suddendeaths from heart-disease. Their proposal is interesting but wequestion whether the platelet aggregation was related to theneuraminidase activity of the virus. We have been studying theeffects of neuraminidase and of viruses with neuraminidase

activity on platelet function ;2-4 we find that purified neura-minidase does not cause a platelet-release reaction nor induceplatelet aggregation. We did not find that desialylated plateletsaggregated spontaneously in homologous plasma, and it seemslikely that the spontaneous aggregation observed by Hovigs isattributable to impurities in the neuraminidase preparationsavailable in 1965, or to the platelet preparation procedures inuse at that time. However, we have found that platelets fromwhich membrane sialic acid has been removed by neuramini-dase show slightly enhanced sensitivity to platelet-aggregatingagents.3 In experiments with animals, these platelets are

rapidly removed from the circulation. Influenza A virus PR8(which has neuraminidase activity) also removes surface sialicacid from platelets without inducing the release reaction orcausing aggregation.4 In animals platelets which have beenexposed to this virus and returned to the circulation also donot survive in the circulation. Therefore it may be that the

reports of thrombocytopenia in association with influenza areattributable to removal of platelet membrane sialic acid by in-fluenza virus. In contrast, there are some viruses (such as New-castle disease virus) which have neuraminidase activity butalso induce the platelet-release reaction and platelet aggrega-tion.4 Viruses with multiple effects of this nature probablyinduce thrombocytopenia by causing platelet-aggregate forma-tion in the circulation and also by removing platelet-membranesialic acid. It seems likely that the swine influenza vaccine studiedby Rivard and Potier induced platelet aggregation in vitrothrough a mechanism unrelated to its neuraminidase activity.We have tested the bivalent influenza virus vaccine pro-

duced by Connaught Laboratories, Downsview, Ontario (lotno. 2807-1) and found that it caused extensive biphasic aggre-gation of washed human platelets and release of 60% of thecontents of the amine storage granules (see table). The aggre-gating activity was abolished by dialysis and could be restoredby adding the preservative in the vaccine (0.01% thimerosal

1. Rivard, G. E., Potier, M. Lancet, 1977, ii, 302.2. Turpie, A. G. G., Chernesky, M. A., Larke, R. P. B., Packham, M. A., Mus-

tard, J. F. Lab. Invest. 1973, 28, 575.3. Greenberg, J., Packham, M. A., Cazenave, J.-P., Reimers, H.-J., Mustard,

J. F. ibid. 1975, 32, 476.4. Scott, S., Reimers, H.-J., Chernesky, M., Greenberg, J. P., Kinlough-Rath-

bone, R., Packham, M. A., Mustard, J. F. Circulation, 1976, 54, 199.5. Hovig, T. Thromb. Diath. hœmorrh. 1965, 13, 84.6. Jamieson, G. A., Pepper, D. S. in The Circulating Platelet (edited by S. A.

Johnson); p. 189. New York, 1971.7. Mustard, J. F., Perry, D. W., Ardlie, N. G., Packham, M. A. Br. J. Hœmat.

1972, 22, 193.8. Leone, G., Boni, P., Vincenti, A. Thrombos. Hæmostas. 1976, 35, 249.9. Kinlough-Rathbone, R. L., Packham, M. A., Mustard, J. F. Thromb. Res.

1976, 9, 669.