317

Letters

to

Week 4.--Control week 2. Week 5.-Treatment week 2:

the Editor

indomethacin 50

mgx3+p.G.

or

placebo.

patients received p.G.E’2 1 mgx3, five P.G.E.2 0.33 mgx3, and the remaining five had 15(R), 15 Me-P.G.E’2 40 p.gx3. Medication with non-steroidal antiinflammatory drugs (N.S.A.I.D.), was discontinued one week before entry to the trial and only paracetamol (acetaminophen) was thereafter allowed as an analgesic supplement. Joint status was examined by a rheumatologist before and at the end of each treatment period. Ten

INFLUENZA VACCINATION POLICY

SIR,-Dr Hoskins and colleagues (Jan. 6, p. 33) drawing on years’ experience at Christ’s Hospital, question the

several

validity of annual vaccination against influenza in schools. Comparable studies at Rugby School confirm the Christ’s Hospital figures. In December, 1968, a monovalent H3N2 saline vaccine was offered to the school, with an acceptance-rate of 85-2% in the boarders. This provided remarkable herd immunity on exposure to the H3N2 influenza virus in mid-January, 1969. An attack-rate of 1.6% was recorded.’ However, the return of the H3N2 virus in December, 1969 showed that the vaccine given in December, 1968, gave no protection at 12 months, while the boys who had received the vaccine by intranasal spray seemed to have an increased susceptibility to the H3N2 virus at 12 months. Influenza vaccine was not again used in the school until autumn, 1973. A commercial vaccine was then offered annually for 3 years. The composition of these vaccines was (in

Stools were collected for measurement of blood-loss on the last 3 days of each control and treatment period. The daily fxcal blood-loss during control week 1 was in the three groups, 0.8±0.3, 0.6±0.1, and 08±05 ml, respectively, and increased significantly during treatment with indomethacin + placebo (see table). Indomethacin-induced bleeding was reduced by prostaglandin E2, especially at the higher dose, and by the methyl analogue (see table). Supplementation

FACAL BLOOD-LOSS IN RHEUMATIC PATIENTS DURING

TREATMENT WITH INDOMETHACIN COUPLED WITH PLACEBO OR A PROSTAGLANDIN

i.u.): in December, 1973, A/Eng/42/72 400, B/Berk/1/71 200, and B/HK/8/73 200; in December, 1974, A/PC/1/73 400, and B/HK/8/73 240, and in December, 1975, A/Scot/840/74 400, A/PC/1/73 400, and B/HK/8/73 360. Acceptance-rates for the vaccines were42.5%, 56.8%, and 62-1%, respectively. The school had two outbreaks of influenza during this per69 cases of H3N2 (Port Chalmers) influenza in the Lent term 1974, and a mixed outbreak of 149 cases of A/Victoria/3/75, A/Eng/864/75, and B/Hong Kong/8/73 in the Lent term, 1976. 103 boys remained unvaccinated, 42 were attacked in one or other outbreak, an attack-rate of 40.8%. 134 boys were vaccinated annually (three times), 50 were attacked in one or other outbreak, an attack-rate of

iod-namely,

Values

37.3%. Annual vaccination against influenza confers no advantage on the individual. At best, vaccination postpones at attack of influenza. More unfortunately, the transient vaccinal protection can prevent the development of the long-term immunity resultant from an attack of influenza. Sanatorium, Rugby School, Rugby CV22 5DD

J.

P. SPARKS

MUCOSAL PROTECTION BY PROSTAGLANDIN E2

SIR,-Dr Cohenhas suggested that aspirin-induced bleeding from the gastrointestinal tract can be prevented by oral prostaglandin E2 (P.G.E.2). In response to the questions left at the end of his letter we should like to report experience with smaller oral doses of P.G.E.2 and its methyl analogue, 15(R), 15-Me-p.G.E.2, to prevent indomethacin-induced gastrointestinal bleeding in patients with rheumatic diseases. The 5’Cr-labelled erythrocyte technique’ was used to monitor fxcal blood-loss in twenty male outpatients, aged 22-61 years who served as their own controls during a 5-week trial. The diagnoses were pelveospondylitis in seven, reactive arthritis in twelve, and rheumatoid arthritis in one. P.G. and placebo were administered in cross-over double-blind fashion and in randomised order, and the trial was designed as follows: Week 1.-Control week 1. Week 2.-Treatment week 1:

indomethacin 50

placebo.

1. Sparks, J. P. Jl. R. Coll. Physns, 1978, 12, 441. 2. Cohen, M. M. Lancet, 1978, ii, 1253. 3. Mollison, P. L., Veall, M. Br. J. Hœmat. 1955, 1, 62.

mgx3+p.G.

as

mean +

s.E.M.

with P.G. was without side-effects and did not reduce the beneficial effect of indomethacin on joint symptoms or status. Damage of the gastrointestinal mucosa induced by N.S.A.I.D. in laboratory animals can be prevented by local administration of p.G.4 Such a protective action has now been demonstrated also in man for p.G.E.2 and a methyl analogue of P.G.E’2 in oral doses small enough not to give side-effects. The protective effect of P.G. is unrelated to gastric-acid secretion since this is not inhibited by oral P.G.E.2.’ 15(R), 15-Me-p.G.E’2 is reported to give few systemic effects,4 and the dose 40 p.g is insufficient to inhibit pentagastrin-stimulated gastric-acid secretion.’ The protection might be related to the dose-dependent mucusstimulatory properties of P.G.’ Our findings may have clinical applications in that untoward effects of N.S.A.I.D. might be avoided by concomitant intake of a low oral dose of P.G.E.2 or its methyl analogue. It is important that such a supplementation should not reduce the beneficial effect of N.S.A.I.D. in rheumatic disease. Gastrointestinal Unit,

Department of Medicine, and Department of Rheumatology,

C. JOHANSSON

Karolinska Hospital, Stockholm, Sweden

B. KOLLBERG R. NORDEMAR

Department of Chemistry, Karolìnska Institute

S. BERGSTRÖM

or

4. Robert, A. in Advances in Prostaglandin and Thromboxane Research (edited by B. Samuelsson and R. Paoletti); vol. II, p. 507. New York, 1976. 5. Karim, S. M. M., Carter, D. C., Bhana, D., Genesan, P. A. Br. med. J. 1973,

1, 143. 6. 7.

Kollberg, B., Johansson, C. Scand. J. Gastroent. (in the press). Johansson, C., Kollberg, B. Eur. J. clin. Invest. (in the press).

Influenza vaccination policy.

317 Letters to Week 4.--Control week 2. Week 5.-Treatment week 2: the Editor indomethacin 50 mgx3+p.G. or placebo. patients received p.G.E’2...
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