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SURGICAL IMPORTANCE OF PLASMA PROTEINS
194
known carcinogenic action of certain sterols further work is required to determine whether carcinogenic substances are produced by the action of ultraviolet light on naturally occurring sterols. Certain other experimental lines of investigation are also suggested by the cancer-producing action of ultraviolet light. Ultraviolet light, together with X rays and radium, both of which are carcinogenic, is one of the most commonly used methods of inducing mutations in the chromosomes of the germ cells. Recently Mackenzie and Muller20 have shown that the wave-lengths producing such mutations in drosophila lie between 3000 and 3200A and do not appear to injure the chromosomes. Does ultraviolet light function in a similar manner in inducing skin cancer or is it necessary to confine the term mutation to hereditary changes confined to the chromosomes ? In viruses such as those of tobacco mosaic, yellow fever and the rabbit fibroma hereditary variations in every way analogous to true mutations have been described, although at the level of organisation of the viruses chromosomes are unknown (cf. Findlay 21). In the case of the tobacco mosaic virus, Stanley22 has shown that different strains of the virus protein differ in their chemical properties, while Knight and Stanley 23 have recently obtained definite information concerning some of the structural differences that exist between variant strains of the tobacco mosaic yirus. It is therefore not too much to hope that before long it will be possible to produce a true mutation by chemical manipulation of the-* tobacco mosaic virus
molecule. Finally, ultraviolet light cancer suggests a third possibility. Is the action of ultraviolet light on the skin merely one of bringing to light and localising an indigenous virus ? Lambeau ’24 for instance, has shown that a latent zoster virus may be activated and localised by treatment with ultraviolet " light. Suggestive evidence of an indigenous cancer virus has lately been brought forward by " Bittner 25 who has found that a factor present in spontaneous mouse cancer, as well as in mouse spleen and milk, can be frozen and dried. When fed to mice of a low cancer-producing strain the incidence of mammary cancer is greatly reduced. There is much to be done, as a modern poet has said, in " the gradual exploring of all the octaves of radiation." "
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"
"
1. Unna, P. G.: Histopathology of diseases of the Skin, Edinburgh, 1896, p. 719.—2. Findlay, G. M. : Lancet, 1928, 2, 1070.— 3. Ibid, p. 1263.—4. Ibid, 1930, 1, 1229.—5. Putschar, W. and Holtz, F.: Z. Krebsforsch. 1930, 33, 219.-6. Herlitz, C. W., Jundell, I. and Wahlgren, F.: Acta paediatr. Stockh. 1931, 10, 321; Wahlgren, Acta path. microbiol. scand. 1932, suppl. 11, p. 166.-7. Huldschinsky, K.: Dtsch. med. Wschr. 1933, 59, 530.— 8. Roffo, A. H.: Bol. Inst. Med. exp. Cancer, B. Aires, 1933, 7, 22; Zbl. allg. Path. path. Anat. 1935, 62, 324.—9. Beard, H., Boggess, T. S. and von Haam, E.: Amer. J. Cancer, 1936, 27, 257.—10. Strahlentherapie, 1939, 66, 329.—11. Rusch, H. P., Kline, B. E. and Baumann, C. A.: Arch. Path. 1941, 31, 135.-12. Büngeler, W.: Z. Krebsforsch. 1937, 46, 130.-13. Kohn-Speyer, A. C.: Lancet, 1929, 2, 1305.—14. Taussig, J., Cooper, Z. K. and Seebig, M. G.: Surg. Gynec. Obstet. 1938, 66, 989.—15. Doniach, I. and Mottram, J. C. : Amer. J. Cancer, 1940, 39, 234.-16. Proc. Soc. exp. Biol., N.Y. 1939, 42, 508.-17. Verh. dtsch. path. Ges. 1934, 27, 102.—18. Amer. J. Cancer, 1939, 35, 213.-19. Bol. Inst. Med. exp. Cancer, B. Ayres, 1935, 12, 529; 583.—20. Mackenzie, K. and Muller, H. J. Proc. Roy. Soc. Lond. 1940, Series B, 129, 491.—21. Doerr and Hallauer’s Handbuch der Virusforschung, 1939, Vienna, vol. II, p. 861.—22. Stanley, W. M.: J. biol. Chem. 1937, 117, 325.—23. Knight, C. A. and Stanley: J. biol. Chem. 1941, No. 139, lxx.—24. Lambeau, P.: Ann. Méd. phys. 1939, 32, 52.—25. Bittner, J. J.: Science, 1941, 93, 527.
death is announced
Aug. 10 of Sir ALFRED in ordinary to Princess Beatrice and medical director of the- Princess Beatrice Hospital for Officers. He was 85. THE
RICE-OXLEY, late
on
physician
Annotations SURGICAL
IMPORTANCE
OF
PLASMA
PROTEINS
THE extraordinary slowness with which practice follows knowledge in medicine is nowhere more evident than in the study of the body proteins. In a paper discussing the replacement of plasma protein lost in burns, Elman1 points out that dehydration and blood concentration in severe burns had already been recognised in 1855by Buhl, and in 1881 Tappeiner had suggested the transfusion of serous fluid for the treatment of these cases. Our knowledge of the functions of the plasma proteins in maintaining the fluid in the vessels was given a scientific basis by Starling in 1896. Now, after nearly 100 years of haphazard research, mostly uncoordinated, we have at last reached an era where the
body proteins are receiving some recognition ; surely a powerful argument for some responsible body to correlate, verify ’and pass into practice as rapidly as possible the results of individual researches. Judging by the vast literature which has accumulated on the subject during the last few years, much energy, time and paper would have been saved by such coordination. The work done from the surgical aspect has been excellently summarised by Ravdin,2 who discusses the various effects of hypoproteinaemia. This condition alone can slow down intestinal movements, and delay the emptying of the stomach. After intestinal operations, the tendency to oedema all over the body consequent on the reduction of plasma protein becomes intensified at the site of opera.tion, causing swelling at the suture line even to the extent of physical obstruction of the bowel. Further, the actual healing of wounds depends on adequate protein reserves, for a lowered plasma protein prevents normal fibroblastic proliferation, thus causing sutured tissues to fall apart when the stitches are absorbed-an accident well known to all abdominal surgeons. The effect of carbohydrate feeding in preventing damage to the liver ’due to some anaesthetics is possibly due to the proteinsparing action of carbohydrate, and liver protection could as well be brought about by adequate protein feeding. The pernicious practice of starving patients before (and after) operations must, in the light of this knowledge, have been the cause of much unnecessary mortality and morbidity. A rather more subtle point emerges. If, as Ravdin points out, it is possible to damage the liver by protein starvation, and if, as seems likely, the liver is chiefly concerned with protein metabolism and regeneration,3 might not a vicious cycle be started by the initial protein depletion ? And to what extent may this cycle be broken by plasmatransfusionP It is clear that some rapid and accurate method suitable for universal use is required for the estimation of the plasma-protein percentage and the amount of the total circulating protein. The latter is the more important because in the presence of uncorrected anhydrsemia (as in burns) the plasma-protein percentage may be normal though the total plasma protein may be greatly reduced along with the reduction of plasma volume. One danger remains to be remembered during the intravenous infusion of plasma. The method at present much used for the production of plasma by the citrate method causes a serious dilution of the plasma by the citrate solution, with the result that the final concentration of protein may be halved. This citrated plasma, if run too quickly into a vein, may cause pulmonary oedema. If the danger of reactions can be removed from serum, this substance, which is undiluted, should be
preferred. 1. Elman, R. J. Amer. med. Ass. Jan. 18 1941, p. 213. 2. Ravdin, I. S. Ann. Surg. 1940, 112, 576. 3. Loeb, R. F. New Engl. J. Med. June 5, 1941, p. 980.
known carcinogenic action of certain sterols further work is required to determine whether carcinogenic substances are produced by the action of ultraviolet light on naturally occurring sterols. Certain other experimental lines of investigation are also suggested by the cancer-producing action of ultraviolet light. Ultraviolet light, together with X rays and radium, both of which are carcinogenic, is one of the most commonly used methods of inducing mutations in the chromosomes of the germ cells. Recently Mackenzie and Muller20 have shown that the wave-lengths producing such mutations in drosophila lie between 3000 and 3200A and do not appear to injure the chromosomes. Does ultraviolet light function in a similar manner in inducing skin cancer or is it necessary to confine the term mutation to hereditary changes confined to the chromosomes ? In viruses such as those of tobacco mosaic, yellow fever and the rabbit fibroma hereditary variations in every way analogous to true mutations have been described, although at the level of organisation of the viruses chromosomes are unknown (cf. Findlay 21). In the case of the tobacco mosaic virus, Stanley22 has shown that different strains of the virus protein differ in their chemical properties, while Knight and Stanley 23 have recently obtained definite information concerning some of the structural differences that exist between variant strains of the tobacco mosaic yirus. It is therefore not too much to hope that before long it will be possible to produce a true mutation by chemical manipulation of the-* tobacco mosaic virus
molecule. Finally, ultraviolet light cancer suggests a third possibility. Is the action of ultraviolet light on the skin merely one of bringing to light and localising an indigenous virus ? Lambeau ’24 for instance, has shown that a latent zoster virus may be activated and localised by treatment with ultraviolet " light. Suggestive evidence of an indigenous cancer virus has lately been brought forward by " Bittner 25 who has found that a factor present in spontaneous mouse cancer, as well as in mouse spleen and milk, can be frozen and dried. When fed to mice of a low cancer-producing strain the incidence of mammary cancer is greatly reduced. There is much to be done, as a modern poet has said, in " the gradual exploring of all the octaves of radiation." "
"
"
"
1. Unna, P. G.: Histopathology of diseases of the Skin, Edinburgh, 1896, p. 719.—2. Findlay, G. M. : Lancet, 1928, 2, 1070.— 3. Ibid, p. 1263.—4. Ibid, 1930, 1, 1229.—5. Putschar, W. and Holtz, F.: Z. Krebsforsch. 1930, 33, 219.-6. Herlitz, C. W., Jundell, I. and Wahlgren, F.: Acta paediatr. Stockh. 1931, 10, 321; Wahlgren, Acta path. microbiol. scand. 1932, suppl. 11, p. 166.-7. Huldschinsky, K.: Dtsch. med. Wschr. 1933, 59, 530.— 8. Roffo, A. H.: Bol. Inst. Med. exp. Cancer, B. Aires, 1933, 7, 22; Zbl. allg. Path. path. Anat. 1935, 62, 324.—9. Beard, H., Boggess, T. S. and von Haam, E.: Amer. J. Cancer, 1936, 27, 257.—10. Strahlentherapie, 1939, 66, 329.—11. Rusch, H. P., Kline, B. E. and Baumann, C. A.: Arch. Path. 1941, 31, 135.-12. Büngeler, W.: Z. Krebsforsch. 1937, 46, 130.-13. Kohn-Speyer, A. C.: Lancet, 1929, 2, 1305.—14. Taussig, J., Cooper, Z. K. and Seebig, M. G.: Surg. Gynec. Obstet. 1938, 66, 989.—15. Doniach, I. and Mottram, J. C. : Amer. J. Cancer, 1940, 39, 234.-16. Proc. Soc. exp. Biol., N.Y. 1939, 42, 508.-17. Verh. dtsch. path. Ges. 1934, 27, 102.—18. Amer. J. Cancer, 1939, 35, 213.-19. Bol. Inst. Med. exp. Cancer, B. Ayres, 1935, 12, 529; 583.—20. Mackenzie, K. and Muller, H. J. Proc. Roy. Soc. Lond. 1940, Series B, 129, 491.—21. Doerr and Hallauer’s Handbuch der Virusforschung, 1939, Vienna, vol. II, p. 861.—22. Stanley, W. M.: J. biol. Chem. 1937, 117, 325.—23. Knight, C. A. and Stanley: J. biol. Chem. 1941, No. 139, lxx.—24. Lambeau, P.: Ann. Méd. phys. 1939, 32, 52.—25. Bittner, J. J.: Science, 1941, 93, 527.
death is announced
Aug. 10 of Sir ALFRED in ordinary to Princess Beatrice and medical director of the- Princess Beatrice Hospital for Officers. He was 85. THE
RICE-OXLEY, late
on
physician
Annotations SURGICAL
IMPORTANCE
OF
PLASMA
PROTEINS
THE extraordinary slowness with which practice follows knowledge in medicine is nowhere more evident than in the study of the body proteins. In a paper discussing the replacement of plasma protein lost in burns, Elman1 points out that dehydration and blood concentration in severe burns had already been recognised in 1855by Buhl, and in 1881 Tappeiner had suggested the transfusion of serous fluid for the treatment of these cases. Our knowledge of the functions of the plasma proteins in maintaining the fluid in the vessels was given a scientific basis by Starling in 1896. Now, after nearly 100 years of haphazard research, mostly uncoordinated, we have at last reached an era where the
body proteins are receiving some recognition ; surely a powerful argument for some responsible body to correlate, verify ’and pass into practice as rapidly as possible the results of individual researches. Judging by the vast literature which has accumulated on the subject during the last few years, much energy, time and paper would have been saved by such coordination. The work done from the surgical aspect has been excellently summarised by Ravdin,2 who discusses the various effects of hypoproteinaemia. This condition alone can slow down intestinal movements, and delay the emptying of the stomach. After intestinal operations, the tendency to oedema all over the body consequent on the reduction of plasma protein becomes intensified at the site of opera.tion, causing swelling at the suture line even to the extent of physical obstruction of the bowel. Further, the actual healing of wounds depends on adequate protein reserves, for a lowered plasma protein prevents normal fibroblastic proliferation, thus causing sutured tissues to fall apart when the stitches are absorbed-an accident well known to all abdominal surgeons. The effect of carbohydrate feeding in preventing damage to the liver ’due to some anaesthetics is possibly due to the proteinsparing action of carbohydrate, and liver protection could as well be brought about by adequate protein feeding. The pernicious practice of starving patients before (and after) operations must, in the light of this knowledge, have been the cause of much unnecessary mortality and morbidity. A rather more subtle point emerges. If, as Ravdin points out, it is possible to damage the liver by protein starvation, and if, as seems likely, the liver is chiefly concerned with protein metabolism and regeneration,3 might not a vicious cycle be started by the initial protein depletion ? And to what extent may this cycle be broken by plasmatransfusionP It is clear that some rapid and accurate method suitable for universal use is required for the estimation of the plasma-protein percentage and the amount of the total circulating protein. The latter is the more important because in the presence of uncorrected anhydrsemia (as in burns) the plasma-protein percentage may be normal though the total plasma protein may be greatly reduced along with the reduction of plasma volume. One danger remains to be remembered during the intravenous infusion of plasma. The method at present much used for the production of plasma by the citrate method causes a serious dilution of the plasma by the citrate solution, with the result that the final concentration of protein may be halved. This citrated plasma, if run too quickly into a vein, may cause pulmonary oedema. If the danger of reactions can be removed from serum, this substance, which is undiluted, should be
preferred. 1. Elman, R. J. Amer. med. Ass. Jan. 18 1941, p. 213. 2. Ravdin, I. S. Ann. Surg. 1940, 112, 576. 3. Loeb, R. F. New Engl. J. Med. June 5, 1941, p. 980.