548

velopment of a cytomegalovirus (human herpesvirus 5) vaccine, although it has not been implicated in neoplasms. On the other hand, there is considerable evidence for a close association between hepatitis B virus and primary hepatocellular

HEADACHE AFTER LUMBAR PUNCTURE

carcinoma.7-1O It has therefore been

suggested" that before of the subunit 20 trials nm scale hepatitis B vaccines are large undertaken, particularly in young children in the developing countries (Maupas et al.12), it is essential to ensure that any benefit that accrues from immunisation is not outweighed by undesirable and potentially serious hazards. There is, therefore, a need to proceed cautiously with the design, purification, development, and preparation of safe and effective vaccines against human hepatitis B, such as the 20 nm surface antigen particle vaccines and the alternative hepatitis B polypeptide vaccines. 13-15 W.H.O. Collaborating Centre for Reference and Research on Viral Hepatitis, Department of Medical Microbiology, London School of Hygiene and Tropical Medicine, London WC1E 7HT

ARIE J. ZUCKERMAN

D.D.A.V.P. AND HEADACHE AFTER LUMBAR PUNCTURE

SIR,-the frequency of headache after lumbar puncture has reported to be about 25%.’ In an attempt to prevent such headaches, prophylaxis with vasopressin has been tried2on the grounds that the antidiuretic action of vasopressin would retain fluid in the cerebrospinal-fluid system. However, the side-effects of vasopressin, including diarrhoea, abdominal

been

cramps, and

sweating, greatly limit its usefulness. In the synarginine-vasopressin analogue D.D.A.v.P. (1-desamino-8D-arginine-vasopressin), the antidiuretic action has been in-

thetic

creased and the vasopressor effect decreased with fewer side-effects. The structural alteration has also increased the half-life of the drug. D.D.A.v.P. has been tested as a prophylactic agent against lumbar-puncture headache in an open study3 with encouraging results. To evaluate this effect under controlled conditions, it is important to use healthy volunteers with no underlying disorders which might induce headache per se. We have done

study the effect OfD.D.A.V.P. with on compared placebo lumbar-puncture headache in sixteen physically and mentally healthy male volunteers (median age 28 years, range 20-48). Two samples of 12 ml C.S.F. were drawn by lumbar puncture between 8 and 9 A.M. with a 2-week interval between the two samples. This study was part of a larger project on c.s.F. endorphins. Immediately after the lumbar puncture, either D.D.A.v.P. 6 g or saline was injected i.m. in a double-blind cross-over design. The volunteers had to lie down for 3 h after the puncture, but thereafter physical activity was not restricted. Headache after lumbar puncture was self-rated after 1 and 3 h and then daily between 8 and 9 A.M. for 4 consecutive days on a "100 mm line", where 0 indicated no headache and 100 indicated severe, intractable headache. The distance in mm between the zero point and the mark made by the subject constitute the intensity of the headache.4 The a

double-blind

on

Szmuness, W. Prog. med. Virol. 1978, 24, 40. Zuckerman, A. J. Trans. R. Soc. trop. Med. Hyg. 1978, 71, 459. 9. Trichopoulos, D., Tabor, E. Gerety, R. J., Xirouchaki, E., Sparros, L., Munoz, N., Linsell, C. A. Lancet, 1978, ii, 1217. 10. Bassendine, M. F., Chadwick, R. G., Lyssiotis, T., Thomas, H. C., Sherlock, S., Cohen, B. J. Br. med. J. 1979, i, 166 11. Zuckerman, A. J. Nature, 1978, 272, 579. 12. Maupas, Ph., Goudeau, A., Coursaget, P., Drucker, J., Barin, F., Andre, M. in Viral Hepatitis (edited by G. N. Vyas, S. N., Cohen, and R. Schmid); p. 539. Philadelphia, 1978. 13. Hollinger, F. B., Dreesman, G. R., Sanchez, Y., Cabral, G. A., Melnick, 7. 8.

J. L. ibid. p.557. 14.

Peterson, D. L., Chien, D. Y., Vyas, G. N., Nitecki, D., Bond, H. E. ibid.

p. 569. 15. Skelly, J., Howard, C. R., Zuckerman, A. J.J. gen. 1. 2.

Virol.

(in the press).

Wolff, H. G. Headache and Other Pain. New York, 1963. Aziz, H., Pearce, J., Miller, E. Br. med. J. 1968, iv, 677. 3. Durward, W. F., Harrington, H. Lancet, 1976, ii, 1403. 4. Zealley, A. K., Aitken, R. C. B. Proc. R. Soc. Med. 1969, 62, 993.

results were categorised as no headache (0 mm), moderate headache (1-50 mm), or severe headache (> 50 mm). Of the sixteen volunteers (eight started with D.D.A.V.P. and eight with placebo injection), nine completed the study with two lumbar punctures. The remaining seven had severe headache after the first lumbar puncture and the second one was not done. Of these seven volunteers, five had had placebo and two had had D.D.A.V.P. after the puncture. 25 lumbar punctures were done, 11 with D.D.A.V.P. cover and 14 with placebo. The table shows the frequency and intensity of the headaches recorded. Severe headache was more frequent in the placebo group (43%) than in the D.D.A.v.P. group (18%). The D.D.A.V.P. group recorded no headache more often (64%) than did the placebo group (36%). However, the difference between the D.D.A.V.P. and placebo effects was not statisti-

cally significant (chi-squared test; p>0.05). The headache was most pronounced 2-3 days after the lumbar puncture, and in a few cases it lasted for 7 days. No sideeffects related to D.D.A.V.P. treatment were observed. Our series is small and the results should be interpreted with caution; however, this study does indicate that D.D.A.V.P. might reduce the frequency and/or the intensity of headache after lumbar puncture. Psychiatric Research Centre, University of Uppsala, 750 17 Uppsala 17, Sweden

ERIK WIDERLÖV LEIF LINDSTRÖM

HLA-DRw4 AND RHEUMATOID ARTHRITIS

SIR,- The HLA antigen DRw4 is unusually common in patients with rheumatoid arthritis (R.A.). Roitt et a1.5 reported on the association between DRw4 and seropositive R.A. and we have investigated the frequency of DRw4 antigen in patients with the seropositive compared with seronegative R.A. HLA-typing was carried out on 39 inpatients with classical in or definite6 R.A. 24 patients were seropositive (titre >32 Rose-Waaler reaction) and 15 patients were seronegative (titre < 16 in Rose-Waaler reaction and negative latex test for rheumatoid factor). HLA typing was done by microcytotoxicity technique with 87 highly selected sera defining 13, 21, 4, and 8 antigens of the A, B, C, and DR series, respectively.’ Only the results of typing for the DRw4 antigen are given in the table. The frequency of DRw4 in the seropositive group was 54% compared with 27% expected (r

D.D.A.V.P. and headache after lumbar puncture.

548 velopment of a cytomegalovirus (human herpesvirus 5) vaccine, although it has not been implicated in neoplasms. On the other hand, there is consi...
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