HYPERTENSION IN THE ELDERLY

164 born in May, 1985. There was no engorgment of the irradiated breast and the patient could not express any milk from this side. Neither patient produced milk from the irradiated breast. However, breast feeding from the unirradiated side was successful and the babies gained weight at the expected rate. We conclude that lactation is not likely to occur from irradiated breasts and every care must be taken to reduce the dose to the unaffected side. Regional Centre for Radiotherapy and Oncology, St Luke’s Hospital, Guildford, Surrey GU1 3NT 1. Max

COMPARISON OF ABILITY OF HUMAN ANTISERUM

(KLB) AND

ANTI-VEROTOXIN RABBIT ANTISERUM TO NEUTRALISE VEROTOXIC S DYSENTERIAE ACTIVITY IN CULTURE FILTRATES OF E COLI AND

TYPE I

1 1

I

A. Y. ROSTOM S. O’CATHAIL

MH, Klamer TW. Pregnancy and breast cancer. South Med J 1983; 76: 1088-90.

HYPERTENSION IN THE ELDERLY

SIR,-Lancet readers will be aware of the debate stimulated by the report of the European Working Party on High Blood Pressure in the Elderly (EWPHE).1 At informal meetings experts have been giving their interpretation of the report for a more general audience but a worrying feature has been the tendency of speakers to extrapolate too far from the findings of the EWPHE, in particular to the suggestion that blood pressure be lowered with,agents other than those used in that trial. While such extrapolation may be logical for some agents, it should not be applied to beta blockers. Some of those who speak on the pharmacology and efficacy of antihypertensive drugs may not have the same insight into adverse effects of drugs in the elderly as other doctors, such as general practitioners. Until there is firm evidence to the contrary perhaps we should rely on Opie’s view2 that the use of any beta blocker in the elderly should be avoided unless it is essential. He felt not only that elderly hypertensives do not respond to beta blockers but also that all side-effects are increased in this age group. DAVID CLINCH

Southampton General Hospital, Southampton SO9 4XY 1.

A. DEMISSIE

Amery A. Birkenhäger W, Brixko P, et al. Mortality and morbidity results for the European Working Party on High Blood Pressure in the Elderly Trial. Lancet 1985;

i 1349-54. 2. Opie LH. Drugs and the heart Lancet

1980; i: 693-98.

ANTIGENIC HETEROGENEITY OF ESCHERICHIA COLI VEROTOXINS

SiR,-Dr Scotland and colleagues (Oct 19, p 885) report that verotoxin (VT)-producing Escherichia coli (VTEC) 0157 elaborates at least two serologically distinct cytotoxins, VT1 and VT2. They also provide evidence that both toxins may be present in a single strain. Their findings are especially relevant to diagnosis, where serologically specific confirmation of cytotoxic activity in faecal, filtrates and bacterial extracts is necessary. We have further evidence for antigenic heterogeneity among E coli VTs. Our findings were stimulated by the observation that human convalescent anti-VT sera show a much broader spectrum of VTneutralising activity than do sera raised in toxoid-immunised rabbits. We have demonstrated an association between haemolytic uraemic syndrome (HUS) and VTEC belonging to several serotypes, including 0157:H7. In our original studies on stools from patients with HUS2 a high-titre anti-VT antiserum from one of our patients was used for neutralising cytotoxic activity in faecal filtrates and bacterial extracts. VTEC serotype 0111 :K58 :nonmotile (strain CL 101) was isolated from this patient (KLB). We subsequently produced a high-titre antiserum to VT in rabbits by immunising them with a toxoid made from purified VT of Konowalchuk’s reference strain H. 303 (serotype 026:K60:H11). This rabbit antiserum and the human KLB serum showed complete cross-neutralisation of their respective VTs. However, the rabbit antiserum did not neutralise several other VT extracts that were neutralised by KLB antiserum. The rabbit and KLB antisera were compared for their neutralising activity against the VTs of strains of several different serotypes using parallel chequerboard titrations.

*HUS=haemolytic

uraemic

syndrome; HC=haemorrhagic

and S. Toma. VT was purified from E coli strain H.30 using O’Bnen and LaVeck’ and Brown et al.’ (M.

colitis. Others

provided by

J. Konowalchuk, C. Gyles, immunised using

adapted from those reported by al unpublished.) Rabbits were glutaraldehyde-treated cytotoxm.VT activity was assayed as described a

method

Petric,

et

prevIOusly.2 titres of the pre-immune and immune rabbit sera, and the KLB determined against H. 30 and CL 101 culture filtrates.2 Both sera had titres of 4096 against their homologous VTs. They were diluted and used m this study at neutralising antibody titres of 256. Culture filtrates of test strains were diluted so that the maximum VT titres were 256. All test strains were E colt except for one (C6352-80) which was a clinical isolate of S dysenterzae type 1. The E coh Isolates were reference strams obtained from J. Konowalchuk’ and C. Gyles (human [h] or porcine [p] source as indicated), and from stools of patients with HUS and haemorrhagic colitis (HC). E coli strains were serotyped by H. Lior, Laboratory Centre for Disease Control, Ottawa.

Neutralising antibody serum were

The results (table) confirmed that the KLB serum had a much broader spectrum of neutralising activity than the rabbit anti-VT antiserum, even though both antisera showed complete crossneutralisation of their own respective VTs. The human serum indicated serological relationship between the VTs from strains CL 12, CL 8, CL 3, CL 106, and HC 6, even though this was not evident in studies with the rabbit anti-VT antiserum. Our findings are therefore consistent with the concept that E coli VTs are a family of probably several distinct cytotoxins that show varying degrees of antigenic relation to each other and also to the shiga toxin.4’SFurthermore, we confirm that the VTs associated with human disease are serologically distinct from those associated with porcine oedema disease(strains E. 57 and P 104). The difference in neutralising capacity between the human and rabbit antisera is probably related to the nature of the antigenic stimulus. The human immune system, during natural infection, is probably exposed to several antigenic determinants on the functional toxin molecule. In contrast, the rabbit immune system is presumably exposed only to restricted antigenic determinants on the glutaraldehyde fixed toxoid which is essentially a highly polymerised protein molecule. Of the VTs from the two strains of E coli 0157:H7 in our study, one (CL 40) was completely neutralised by both the rabbit and human anti-VT antisera, whereas the other (CL 8) was partly neutralised by the human serum but not at all by the rabbit antiserum. This observation is consistent with the report of Scotland and colleagues that there exist two distinct, but serologically related, verotoxins VTl and VT2 in E coli 0157:H7. Even though these toxins were not cross-neutralised by rabbit antisera, they were considered by Scotland and colleagues to share common protein sequences, as indicated by a limited degree of cross-hybridisation between purified VT1 and VT2 DNA probe

fragments. A difference in neutralisation by our rabbit and KLB antisera was also observed with VTs from the two strains (CL 101 and CL 12) of