776 SUBLETHAL INTOXICATIONS 



and is followed in a few hours by a very marked leukocytosis. After lethal doses the leuko- 

 penia may persist until death. 



Infections, both fatal and non-fatal, with certain bacteria, notably the typhoid bacillus, 

 are characteristically associated with a leukopenia. But the injection of sublethal doses of 

 killed typhoid bacilli is followed by a leukocytosis. There is some evidence to the effect that 

 such an injection into an animal which has been immunized against the corresponding bacteria 

 is followed by a more marked increase in the number of leukocytes than occurs after an 

 injection of a non-immune animal. 



Some bacteria produce hemolytic substances. In streptococcal infections from which 

 the patient recovers a marked anemia, often associated with jaundice, is frequently one of 

 the grave clinical manifestations of the disease. Bordet,' Besredka,* and others have de- 

 scribed a hemolysin in filtered broth cultures of streptococcus which will dissolve the er\^thro- 

 cytes of laboratory animals and of man. Whether the anemia which accompanies infections 

 with this micro-organism is due to the specific action of this soluble hemolysin is not certain. 



Reimann and Julianelle^ found that extracts of pneumococci produced a hemorrhagic 

 purpura in mice. This was associated with a marked reduction in the number of blood plate- 

 lets. Regeneration of the platelets was accomplished by the fourth to the ninth day. There 

 was then an overproduction, and the number did not return to normal until several weeks 

 had elapsed. There was also in these animals a diminution in the number of red cells, re- 

 generation of which was considerably slower than the regeneration of the platelets. They 

 concluded that the pneumococcus extracts were both thrombolytic and hemolytic. 



Fever is such a constant accompaniment of infectious diseases that the character 

 of the temperature curve from day to day or from hour to hour is of great diagnostic 

 significance. The effect of injections of toxic bacterial products upon body tempera- 

 ture depends both upon the size of the dose and the micro-organism concerned. Lethal 

 doses and even large sublethal doses cause a fall in temperature. Smaller doses induce 

 a rise in body temperature. Roily and Meltzer^ attempted to reproduce experiment- 

 ally the conditions that occur in spontaneous infections by the repeated injections of 

 very small amounts of bacteria or their toxins with the result that a rise in tempera- 

 ture always followed. Vaughan^ was able to reproduce a temperature curve similar 

 in all essential respects to that of typhoid fever by the injection of animals with the 

 protein split products of the t>T3hoid bacillus in suitable doses at proper intervals. 

 Tuberculin causes fever in normal animals if given in sufficiently large doses, but 

 small doses will induce a rise in temperature in tuberculous animals that are sensitive 

 to this poisonous product of the tubercle bacillus. Jona^ produced fever by the injec- 

 tion of a substance extracted from the colon bacillus. Moreschi and Golgi" made ex- 

 tracts of typhoid and tubercle bacilli and of staphylococci by treating them with fresh 

 guinea-pig serum. They found no parallelism between the pyrogenic and the anaphy- 

 lactic value of typhoid "anaphylatoxin." The anaphylatoxin of the tubercle bacillus 



' Bordet, J.: A)m. de Vlnsl. Pasteur, g, 462. 1897. 



* Besredka, A.: ibid., 15, 880. 1901. 



3 Reimann, H., and Julianclle, L. A.: /. Ex per. Med., 43, 97. 1926. 



4 Roily, F., and Meltzer, K. S.: Deutschcs Arch.f. hlin. Mai., 94, 335. 1908. 

 s Vaughan, V. C: Protein Split Products, etc. Philadelphia, 1913. 



^ Jona, J. L.: /. Uyg., 15, 169. 1916. 



7 Moreschi, C, and Golgi, A.: Ztschr.f. Immunltdtsjorsch. 11. c.xpcr. T/icrap., Orig., 19, 623. 1913. 



