78o SUBLETHAL INTOXICATIONS 



the degree of injury being roughly proportional to the size of the dose. He suggested 

 that the localization of the lesions in these capillaries is due to the concentration of 

 the toxin in the blood which follows the loss of water at this point. By the injection 

 of sublethal doses of colon bacilli into rabbits already suffering from a mild grade of 

 glomerular damage following diphtheria toxin, Faber was able to produce a severe 

 form of glomerulonephritis corresponding to the extra-capillary type of Volhard and 

 Fahr. Similar, though not identical, lesions were produced when diphtheria toxin 

 was followed by Vaughan's split protein (poisonous part) of the colon bacillus. Faber 

 believed that bacteriolysis of colon bacilli in the blood stream liberated toxic sub- 

 stances which induced the glomerulonephritis. 



Numerous attempts have been made to produce nephritis by the injection of the 

 toxic products of streptococci, because of the constant presence of these micro- 

 organisms in scarlet fever and because nephritis is such a common complication of 

 this disease. 



Stoddard and Woods' injected rabbits with an extract of streptococci and staphylococci 

 prepared by Macfadyen's method and observed acute degenerative changes in the proximal 

 convoluted tubules of the kidneys which persisted for from two to three weeks. Faber and 

 Murray^ made repeated intravenous injections of streptococci and staphylococci from cases 

 of scarlet fever, and of B. coli, and were unable to produce a typical glomerulonephritis even 

 when immune bodies could be demonstrated in the serum in high dilutions. They were es- 

 pecially interested in this phase of the problem because Volhard and Fahr^ had claimed that 

 it is the characteristic of diffuse nephritis to occur at a time when immune processes are 

 active, making possible a "diffuse toxic action." Von Pirquett and others had attempted to 

 explain the occurrence of nephritis as a complication of scarlet fever on the basis of allergy. 

 Their explanation was as foUows: At the beginning of the disease and during the acute 

 symptoms, the virus circulates in the blood and sensitizes the cells of the body. The immune 

 bodies begin to appear at the end of the second week. At this time a reinvasion of the body 

 from various foci occurs, a specific reaction between antigen and antibody takes place, and 

 this, after the latent period common to allergic reactions, leads to active signs and symp- 

 toms of the sequelae of scarlet fever in the third and fourth weeks. But Faber and Murray^ 

 were unable to verify this view, because they could not demonstrate bacteriolysis of strep- 

 tococci with the serum of highly immunized animals either in vitro or by the Pfeiffer phe- 

 nomenon. They therefore conclude that the weight of evidence is against the theory that 

 glomerulonephritis is due to an immune bacteriolysis of streptococci. 



Bell, Hartzell, and Clawson^ were unable to produce glomerulonephritis in rabbits by 

 the injection of streptococci from human sources. In monkeys similar injections usually 

 induced a severe nephrosis, and in only one instance, a glomerulonephritis. Duval and 

 Hibbard,* however, claim to have produced in rabbits various types of glomerulonephritis, 

 including the epithelial "crescents," endothelial proliferation, hyaline thrombi in the vessels 

 of the glomeruli, hemorrhage into the capsular space, and complete necrosis of the capillary 

 tufts, by the injection of the "toxic principle of the scarlatinal streptococcus of the Dicks." 



' Stoddard, J. L., and Woods, A. C: /. Med. Research, 34, 343. 1916. 



^ Faber, H. K., and Murray, V.: J. Exper. Med., 26, 707. 1917. 



3 Volhard, F., and Fahr, T.: Die Brightsche Krankheit. Berlin, 1914. 



■» V. Pirquet, C. : Ergehn. d. inn. Med. it. Kinderh., 5, 459. 1910. 



5 Bell, E. T., Hartzell, T. B., and Clawson, B. J.: Am. J. Path., i, 247. 1925. 



« Duval, C. W., and Hibbard, R. J.: /. Exper. Med., 44, 567. 1926; J.A.M.A., 87, S98. 1926. 



