288 this compound precipitated with the monoclonal IgM in vitro. Precipitation depends on formation of a lattice between antibody molecules and antigen which at least must be divalent. As expected, the corresponding monovalent compound (sodium acetrizoate) did not precipitate IgM E.O., but reacted with it and inhibited the precipitation reaction between the macroglobulin and the divalent compound (fig. 1). In the passive transfer experiments where the mice obtained a constant amount of macroglobulin and different doses of the divalent compound, the clinical effects corresponded closely to the amount of precipitate obtained in vitro in quantitative precipitin experiments. Injection of sufficient amounts of ioglycamide to induce marked intravascular precipitate formation led to sudden circulatory collapse and death. Histological examination revealed large precipitates in pulmonary

arteries. The monovalent non-precipitating compound did not induce any clinical symptoms and the organs examined were histologically normal. It is thus precipitate formation which gives rise to immediate circulatory collapse. This type of reaction may be induced when monoclonal macroglobulins interact with divalent drugs which contain two groups of similar structure linked by an aliphatic chain, such as ioglycamide acid. Drugs, biological materials, and synthetic products with repeating units of identical structure may also precipitate with monoclonal macroglobulins. Such reactions have been demonstrated in vitro between several monoclonal IgM proteins and type-specific klebsiella polysaccharides13 14 but the consequences in vivo of such reactions have not yet been established. Monovalent compounds which did not precipitate with IgM E.O. had no apparent ill-effects in passive transfer experiments, but we expect that the drug is bound to the IgM in the circulation. This probably results in a different distribution volume and changed catabolism of the drug. The result could easily be decreased activity of the drug. Such effects are probably not restricted to contrast media and should therefore be seriously considered and explored in patients with Wal-

denstr0m’s macroglobulineemia, multiple myeloma,


benign monoclonal gammopathy who show an unexpectedly poor response to drugs. This work was supported by grants from Anders Jahre’s Fund for the Promotion of Science and the Norwegian Council for Science and the Humanities. K.B. was supported by Eisner-Stiftung 1973 and Schering AG. We thank Miss Kirsten Svindahl for excellent technical



Mission médicale du Centre Scientifique et Médical de l’Université Libre de Bruxelles en Afrique Centrale (CEMUBAC) auprès de l’Institut pour la Recherche

Scientifique en Afrique Centrale, Lwiro, Kivu, Zaire, and Laboratoire de Recherches sur la Reproduction Humaine, Hôpital Saint-Pierre, Université Libre de Bruxelles, Belgium

serum-prolactin concentrations high until 15 months post partum in nursing mothers in Central Africa (Lwiro). They were significantly lower in menstruating than in amenorrhœic nursing mothers. These results support the hypothesis that prolactin is involved in the long-lasting amenorrhœa which occurs in regions where breast-feeding is prolonged for up to 2 years after delivery.


REFERENCES 1. Fudenberg, H. H., Kunkel, H. G. J. exp. Med. 1957, 106, 689. 2. Harboe, M., Torsvik, H. Scand. J. Hæmat. 1969, 6, 416. 3. Ashman, R. F., Metzger, H. J. biol. Chem. 1969, 244, 3405. 4. Hannestad, K. Clin. exp. Immun. 1969, 4, 555. 5. Tolleshaug, H., Hannestad, K. Immunochemistry, 1975, 12, 173. 6. Harboe, M. Unpublished. 7. Bauer, K., Trag, K. H., Bauer, G. Wien. klin. Wschr. 1974, 86, 766. 8. Bauer, K., Trag, K. H. Scand. J. Immun. (in the press). 9. Harboe, M., Følling, I. Scand. J. Immun. 1974, 3, 471. 10. Harboe, M., Solheim, B. G., Deverill, J. J. exp. Med. 1969, 129, 1217. 11. Harboe, M., Solheim, B. G. Scand. J. Immun. 1972, 1, 63. 12. Lendrum, A. C., Fraser, D. S., Slidders, W., Henderson, R. J. clin. Path. 1962, 15, 401. 13 Hannestad, K., Eriksen, J., Chnstensen, T., Harboe, M. ibid. 1970, 7, 899. 14. Harboe, M., Deverill, J., Eriksen, J. Acta path. microbiol. scand. 1975, 83, Sect. C., 97.



Introduction POST-PARTum amenorrhoea lasts much longer in populations where breast-feeding is prolonged for up to 24 months than in populations where weaning occurs within 1 to 3 months of birth. Hyperprolactinsemia is associated with amenorrhcea and anovulation.2 We measured serum-prolactin concentrations during prolonged breast-feeding in menstruating and amenorrhoeic women in Central Africa.


collected, between 10 A.M. and 4 P.M., Blood-samples before just breast-feeding and 30 minutes after suckling started from thirty-nine lactating mothers between 1 and 24 months after delivery. As controls, blòod-samples were also were

collected from twenty adult


prolactin, luteinising hormone (L.H.), and follicle-stimulating hormone (F.S.H.) were measured by radioimmunoassays by means of the second-antibody technique.3-5 The L.H. and F.S.H. results were expressed in mi.u./ml (2nd international reference preparation of human menopausal gonadotrophins). The prolactin results were expressed in u/ml (human pituitary prolactin research standard 71/222 distributed by the National Institute for Biological Standards and Control, London). Statistical analyses were conducted after log transformation by means of t tests or paired t tests and linear regression analysis. Serum



Requests for reprints should be addressed to M.H.



Mean basal serum-prolactin was significantly higher in amenorrhoeic nursing mothers than in (P

Serum-prolactin in long-lasting lactation amenorrhoea.

Serum prolactin levels were measured during prolonged breast feeding in menstruating and amenorrheic women in Central Africa. Adult men were controls...
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