HOWARD T. KARSNER 973 



degree of sensitiveness, the size of the shock dose, the condition of the protein, and 

 the method of administration. The rapidity and severity of reaction are greatest fol- 

 lowing intravenous or intracardiac injection and less so following, in order, intra- 

 meningeal, intraperitoneal, and subcutaneous injections. Besredka estimates that, 

 with the use of serum, approximately equivalent reactions may be produced by intra- 

 venous injections of 0.05-0.1 cc, intrathecal injections of 0.066-0.125 cc, and intra- 

 peritoneal injections of 5.0-6.0 cc. Subcutaneous injections in experimental animals 

 rarely produce acute, severe, or fatal reactions. It is obvious that intravenous injec- 

 tions are undesirable when solid proteins, bacteria, and proteins with capacity for 

 direct alteration of the blood are to be employed, because the result may be confused 

 by the occurrence of thrombosis or embolism. 



Anaphylactin is subject to the same deteriorative effects as anaphylactogen. 

 Kato's work, quoted above, indicates that the two are not chemically different. The 

 effectiveness of fresh serum decreases during the first ten days by about 50 per cent. 

 The curve flattens thereafter. Besredka found that a serum twenty years old was still 

 effective, and Uhlenhuth and HaendeP state that the same is true of proteins from 

 Egyptian mummies. 



Individual variations in animals of the same species make it seem advisable to 

 judge of effectiveness only on the basis of fatal reactions (Karsner and Ecker).^ Wells 

 states that blood serum contains so many substances that it can be regarded as an 

 "extract of the animal," an objection that can be overcome only by the use of pure 

 proteins. Much of the reported work is on the basis of serum anaphylaxis, and some 

 of the conclusions may be altered when the use of pure proteins becomes more general. 

 It is said that the size of the minimum intoxicating dose is to the size of the minimum 

 sensitizing dose as 100 to i. In the guinea pig, fatal reactions are rarely obtained with 

 less than 0.02 5-cc. serum, and as a rule much larger amounts are required. Wells re- 

 ports fatal shock with o.oooooi-gm. crystallized egg white. 



Features of shock. — These are to be considered under the headings of "Objective Mani- 

 festations in the Living Animal," "Morbid Anatomical Changes," and "Functional Dis- 

 turbances." 



The clinical manifestations, essentially the same in both forms, are more severe in acute 

 or immediate shock than in the subacute or delayed shock. In immediate shock in the guinea 

 pig there are ruffling of fur, rubbing of nose, evacuation of urine and feces, spasmodic move- 

 ments increasing to violent general convulsions, severe dyspnea, cyanosis, and death from 

 asphyxia with the heart still beating. In the dog and the rabbit, the respiratory and convul- 

 sive phenomena are less evident, the principal feature being marked fall in blood pressure, 

 violent precordial activity, salivation, vomiting, and diarrhea. Parker and Parker^ have 

 found that the white rat behaves much as does the dog. The cat may show pronounced 

 respiratory phenomena but the usual feature is fall of blood pressure (Edmunds) .4 In birds, 

 especially fowl and pigeons, the symptoms are generally the same, associated with marked 



' Uhlenhuth, H., and Haendel, D.: Zlschr. f. Immiinitdtsforsch. u. exper. Therap., 4, 761. 1910 

 (seep. 774). 



2 Karsner, H. T., and Ecker, E. E.: /. Infect. Dis., 30, 333. 1922. 



3 Parker, J. T. and F.: /. Med. Research, 44, 263. 1924. 



4 Edmunds, C. W.: /. Pharmacol. &" Exper. Therap., 5, 518. igi4; Zlschr. f. Immunitatsforsch. 

 u. exper. Therap., 33, 181. 1914. 



