lymphocyte subsets. For example, the classical serologically defined (HLA-A, HLA-B) M.H.C. alloantigens are routinely typed for blood mononuclear cells comprising lymphocytes and monocytes (about 15%), and such antigens may be specifically identified by cytotoxicity testing on enriched adherent populations of blood monocytes or peritoneal macrophages.’Further, since certain strong M.H.C.-associated lymphocyte-activating determinants have been shown by Festenstein et al. to be present on macrophages in the mouse, and the human macrophage has been demonstrated to be a potent stimulator of allogeneic lymphocytes, 1this cell in man presumably expresses HLA-D locus antigens as well. Certainly the proposed mixed-lymphocyte-reaction (M.L.R.)-stimulating la antigens are expressed on the macrophage,6 and similar antigens have been defined by M.L.R.-inhibition in man.7 Little is known about the
relaand the HLA-D gene exact
tionship between these Ia-type antigens products.’ That macrophages may participate in antibody dependent and independent cytotoxicity is clear, and any thought of transfer of large numbers of these "killer" cells may have a certain appeal. Given the above evidence, however, and the fact that macrophages have even been used for the induction of cytotoxic lymphocytes in vitro,9 the Westminster Hospital group’s proposal that such cells may be successfully grafted across an allogeneic barrier is untenable, and perhaps contrary to new findings of macrophage function. 10 Institute of Immunology, University of Toronto, Toronto, Canada M5S 1A8
but certainly not Fallon’s letter.
the extent that could be inferred from Dr
Department of Social and Community Medicine, University of Oxford, 8 Keble Road, Oxford OX1 3QN
INCREASE OF UPPER-LIMB-REDUCTION DEFORMITIES IN HUNGARY
SiR,—Transient increase in the incidence of limb-reduction deformities have been noted in Canada,’ Australia,2U.S.A.,3 and Norway.4 This was not confirmed in other countries (e.g., Birmingham, U.K.5). According to the Hungarian Congenital Malformation Register the point prevalence at birth of upperlimb-reduction defects showed a significant increase in 1974-75 (table). In other anomalies similar trends have not NUMBER
(AND POINT PREVALENCE
UPPER-LIMB-REDUCTION DEFORMITIES AND TOTAL CONGENITAL ANOMALIES IN
D. G. ROMANS *Data
ACUTE BACTERIAL MENINGITIS IN CHILDHOOD
SiR,—Iwould like to comment on the letter from Dr Fallon and his colleagues (Feb. 28, p. 487). My estimate of the risk of having meningitis is that for an individual child by the age of ten years, as stated in my paper (Jan. 3, p. 28). Dr Fallon’s estimate of risk is based on the average annual rate of infection in children under ten years of age (e.g., 344 cases of meningococcal infection in 5 yearscases per annum per 1 in 12 673 children 871900 children under 10 years of age per annum). Not surprisingly, there is about a tenfold difference between our results. Because the age-specific incidence for meningitis is so skewed, I believe that "risk" is best summarised as the risk of having an illness by a given age. However, the most important point is that the incidence of meningococcal and haemophilus meningitis is reasonably similar in the two regions if comparable calculations are done. Assuming an even age distribution in the underlying population and that no child has either illness more than once, the risk (from birth) of having an acute meningococcal infection by the age of ten years can be estimated as 1 in 1267, and that for hmmophilus meningitis as 1 in 2395, from the Ruchill data. This compares with figures of 1 in 1090 and 1 in 1500, respectively, in my study. Thus the incidence of meningococcal infection is strikingly similar. Haemophilus meningitis probably is rather commoner in South-East England than in Scotland,’ =
been found. During the period of 1970-73 the monthly average was 2.1. In 1974 it rose to 4-8. Sex-hormone treatments (oral contraceptive pills immediately before and during early pregnancy6) were studied on these cases and on controls by questionnaires without any positive correlation. In 1975, 7 upper-limb-reduction defects occurred monthly. A particular time or place clustering could not be proved. Improved notification cannot account for this increase. We are now trying to detect the cause(s) by personal interview. Laboratory of Human Genetics, National Institute of Hygiene, Budapest IX, Hungary
2. Schirrmacher, V., Peña-Martinez, J., Festenstein, H. Nature, 1975, 255, 155.
3. Marshall, W. H.,
Rigo, S. J., Melman, S. Lancet, 1966, i, 730. 4. Rode, H. N., Gordon, J. Cell. Immun. 1974, 13, 87. 5. Lozner, E. C., Sachs, D. H., Shearer, G. M., Terry, W. D. Science, 1974, 183, 757. 6. Hämmerling, G. J.,
Mauve, G., Goldberg, E., McDevitt, H. O. Immunogenetics, 1975, 1, 428. 7. van Leeuwen, A., Schuit, H. R. E., van Rood, J. J. Transplant. Proc. 1973, 5, 1539. 8 van Rood, J. J., van Leeuwen, A., Keuning, J. J., Termijtelen, A. ibid. 1975, 7, 31. 9 Wagner, H., Wyss, C. Eur. J. Immun. 1973, 3, 549. 10 Talmage, D. W., Dart, G., Radovich, J., Lafferty, K. J. Science, 1976, 191, 385.
Turk, D. C., May, J. R. Hœmophilus Influenzœ, London,
A. CZEIZEL I. PAZONYI
SIR,-Dr Martin and Mr Powell (March 6, p. 536) observed significantly lower values for plasma-paracetamol estimated by the colorimetric method of Glynn and KendaF compared with results obtained by the spectrophotometric method of Routh et al.8 In a similar series of 22 patients we also compared results by the two procedures but, by paired t test, we found no significant difference between them. We have modified the Glynn and Kendal method by pipetting off a fixed volume of supernatant from the protein precipitate rather than simply decanting. We also use a paracetamol-free serum as a blank and subtract the value obtained for this from the
1. Falk, J. A. Personal communication.
M. J. GOLDACRE
Department of Pathology, North Manchester General Manchester M8 6RB
result. K. WIENER
1. Banister, P. Can. med. Ass. J. 1970, 103, 446. 2. McBride, W. G. Med. J. Aust. 1972, i, 492. 3. Flynt, J. W. Jr. in Congenital Defects. (edited by D. T. Janerich, R. G. Skalko, and H. Porter); p. 119. New York, 1974. 4. Bjerkedel, T. Personal communication. 5. Record, R. G., Armstrong, E. Lancet, 1974, i, 804. 6. Janerich, D. T., Piper, J. M., Glebatis, D. M. New Engl. J. Med. 1974, 291, 697. 7. Glynn, J. P., Kendal, S. E. Lancet, 1975, i, 1147. 8. Routh, J. I., Shane, N. A., Arrendondo, E. G., Paul, W. D. Clin. Chem.
1968, 14, 882.