604

symptoms and signs as in their frequency; whichconfirms the difficulty of differentiation in individualcases. Where doubt remains resection is obligatory.

1. Lancet, 1953, i, 476.2. Tiselius, A. Biochem. J. 1937, 31, 1464.3. Dole, V. P. J. clin. Invest. 1944, 23, 708.4. Lewis, L. A., McCullagh, E. P. Amer. J. med. Sci. 1944, 208, 727.5. Moore, D. H. J. biol. Chem. 1945, 161, 21.6. Seibert, F. B., Seibert, M. V., Atno, A. J., Campbell, H. W.

J. clin. Invest. 1947, 26, 90.7. Whitman, J. F., Rossmiller, H. R., Lewis, L. A. J. Lab. clin.

Med. 1950, 35, 167.8. Martin, N. H. Brit. J. exp. Path. 1946, 27, 363.9. Malmros, H., Blix, G. Acta med. scand. 1946, suppl. 170, p. 280.

10. Marrack, J. R., Hode, H. J. clin. Path. 1949, 2, 161.11. McQueen, E. G., O’Shea, R. F., Summerfield, M. P. Aust. Ann.

Med. 1954, 3, 270.12. Church, D., Blackburn, C. R. B. Ibid, p. 279.13. Mackay, I. R., Volwiler, W. Ibid, p. 263.

INACCURACY IN THE LABORATORY

Two years ago we referred to evidence that differentbiochemical laboratories might report very differentresults of analysis of the same sample.l Since then theInternational Association of Clinical Biochemists hasmade a survey, mainly in America and the countries ofWestern Europe ; and we understand that the findings(not yet published) show that the situation is much thesame in all the countries studied.We suggested that it would be useful if someone sup-

plied accurately analysed blood plasma or serum so thatindividuals could check their own analyses. GlaxoLaboratories Ltd. are now preparing batches of freeze-dried serum, and this material is being analysed bymembers of a joint committee set up by the Associationof Clinical Pathologists and the Association of ClinicalBiochemists. It is proposed to supply figures for the con-tent of sodium, potassium, calcium chloride, urea, glucose,and total protein. The samples are to be distributed byMessrs. C. Davis Keeler Ltd., 39, Wigmore Street,London, W.I, to whom all inquiries should be addressed.Large-scale production, and the good will of the firms con-cerned, have enabled the costs to be kept low, and it isexpected that each sample will cost less than five shillings.

ELECTROPHORESIS OF SERUM-PROTEINS

IN 1937 Tiselius 2 separated the components of the

plasma-proteins by boundary-electrophoretic analysis,and analysis by this method of normal3-7 and patho-logical 4-10 sera has since been often recorded. The

apparatus needed for boundary electrophoresis is com-

plex and expensive, and its use entails much time andtechnical skill. But the development of zone-electro-phoresis on filter-paper, with apparatus which is simpleand cheap, has now brought the electrophoretic methodof protein separation within the reach of most hospitallaboratories.McQueen et aU1 have reviewed the results of paper-

electrophoresis of serum-proteins in several differentdiseases. They conclude that the protein pattern is

specific in collagen diseases, nephrosis, hepatic cirrhosis,and multiple myelomatosis. They have also found thatserial observations are of great value in assessing theprogress and activity of a disease, especially in collagendiseases and infective hepatitis. McQueen et al. suggestthat paper-electrophoresis of the serum-proteins mayreplace the turbidity and flocculation tests for diagnosisand serial assessment of infective hepatitis. This enthu-siasm is not shared by Church and Blackburn,12 whofound that electrophoresis of serum-proteins in cases ofliver disease gave no more information than could havebeen obtained more simply from zinc-sulphate turbiditytests and estimations of total serum-proteins. Mackayand Volwiler 13 point out that the usefulness of paper-strip electrophoresis in routine diagnostic work is limitedby the fact that changes in the serum-protein fractionsare generally non-specific to any particular disease.

Exceptions to this are y-myelomatosis and agammaglo-bulinsemia, where the method may give results of diag-nostic value. Mackay and Volwiler conclude that

"

quantitative reproducibility of paper electrophoreticanalysis of serum appears satisfactory," but they do notclaim the same precision as for boundary electrophoresis.The quantitative accuracy of paper-electrophoresis hasbeen questioned by Martin and Franglen,14 who also

point out that the technique must be very careful ifuseful and reproducible qualitative results are to beobtained. It seems that the application of this methodto clinical work would best be confined to qualitativeassessment of the stained strip by someone experiencedin such work. The results of quantitative analysis areoften inaccurate and may be misleading.

14. Martin, N. H., Franglen, G. T. J. clin. Path. 1954, 7, 87.15. Drinker, C. K., Drinker, K. R., Lund, C. C. Amer. J. Physiol.

1922, 62, 1.16. Doan, C. A. Contr. Embryol. Carneg. Instn, 1922, 14, 27.17. Josefson, A. Acta med. scand. 1934, 81, 550.18. Tocantins, L. M. Proc. Soc. exp. Biol., N.Y. 1940, 45, 292.19. Tocantins, L. M., O’Neill, J. F. Ibid, p. 782.20. Tocantins, L. M., O’Neill, J. F. Surg. Gynec. Obstet. 1941, 73, 281.21. Tocantins, L. M., O’Neill, J. F., Price, A. H. Ann. Surg. 1941,

114, 1085.22. Tocantins, L. M., O’Neill, J. F., Jones, H. W. J. Amer. med.

Ass. 1941, 117, 1229.23. Doud, E. A., Tysell, J. E. Ibid, 1942, 120, 1212.24. Beher, G. Lancet, 1944, ii, 472.25. Henning, N. Dtsch. med. Wschr. 1940, 64, 737.26. Bailey, H. Brit. med. J. 1944, i, 181.27. Pillar, S. New Engl. J. Med. 1954, 251, 846.28. Quilligan, J. J., Turkel, H. Amer. J. Dis. Child. 1946, 71, 457.29. Rooney, E. F. Arch. Pediat. 1944, 61, 611.30. Dardinski, V. J. Med. Ann. D.C. 1945, 14, 206.31. O’Neill, J. F., Tocantins, L. M., Price, A. H. N. C. med. J.

1942, 3, 495.32. Wile, V., Schamberg, I. L. J. invest. Derm. 1942, 5, 173.

INFUSIONS INTO BONE-MARROW

As long ago as 1922 Drinker et al.i5 and Doan," workingindependently, showed that fluids infused into bone-marrow quickly reached the general circulation. Josefsonl7gave patients with pernicious anaemia liver extract by themedullary route ; he noted transient reactions, but

proposed that other drugs should be given by this route.But it was Tocantins et al.18-22 who first made extensiveuse of intramedullary infusions of blood, saline, anddextrose solutions for replacement therapy. This methodhas been used for massive infusions in a case of ulcerativecolitis ; the patient received nearly 23 litres of bloodand saline and dextrose solution into his sternal bone-marrow in nine days.23 Until quite lately intramedullaryinfusions were given into the sternum or, less commonly,into the tibia 24 or femur 25 ; and special instrumentshave been designed for penetrating the bone and deliver-ing the infused fluid.24 26 Pillar 27 has shown by injectionof radio-opaque material into the ilial marrow that theinjected material rapidly reaches the general circulation,thus confirming earlier observations.18 21 He found thatthe crest of the ilium was a good site for infusion, becausethe capillary network inside the marrow is here moreextensive than that in the sternum and most otherbones, and because accidental perforation of the iliumdoes not endanger vital organs. He infused solutionsof the vitamin-B complex, vitamin C, dextrose, andpotassium chloride without ill effect.

Bone-marrow infusion is contra-indicated in cases ofbactersemia or septicemia or even of extensive sepsis,as in generalised peritonitis, because of a realdanger of causing osteomyelitis.28 29 Mediastinitis 30 31and perforation of the posterior table 26 have followedinfusion into the sternum. There is some experimentalevidence that infusion into marrow may cause fat-embolism,32 but this complication has not been reportedin man. Medullary infusion is unsuitable for continuousreplacement or maintenance therapy over any length oftime. Viscous fluids, such as blood, must be infusedunder pressure, so such an infusion needs constant atten-tion. Nevertheless anyone with experience of protractedparenteral maintenance therapy must at some time havewondered whether a patient would die from lack of veinscapable of receiving infusions ; and it is in this type ofcase, and in those where veins are collapsed, thatintra-osseous infusion is of greatest value.