186 PROTEIN THERAPY 



and 466 alternating cases with empty horse serum that is, normal 

 horse serum which contained no antitoxin. The results as far as 

 could be judged in the two series showed no difference in the mortality, 

 in the duration of the illness, or in the number of complications. 

 As a matter of fact Bertin is said to have used injections of normal 

 serum as early as 1895 in diphtheria, and Roily as well as v. Striimpell 

 also employed "empty" serum. In 1912 Lorey again called attention 

 to the subject. 



Attention is called to Bingel's paper not because it describes a 

 desirable mode of procedure that is to be commended, but because 

 of its theoretic and practical importance. There can be no doubt 

 that specific antitoxin will exhibit incomparable superiority over nor- 

 mal horse serum both in practical therapeutic application and in ani- 

 mal experimentation. But in practice the observation of Bingel has 

 been confirmed, even if not in a large series, by Dorn and by Meyer. 

 Klotz has recently reviewed the entire subject. 



There has been an often expressed observation among a number 

 of clinicians during more recent years that the modern highly con- 

 centrated diphtheria antitoxin does not always give the same satis- 

 factory results that our older, less concentrated preparations did. 

 Of the older preparations larger doses of serum had to be injected. 

 The work of Bingel makes clear the basis for this conviction. That 

 is, we are dealing in diphtheria antitoxin with two factors that are of 

 therapeutic value, the specific antitoxin content and the nonspecific 

 stimulating property of the serum proteins. The more highly con- 

 centrated the preparation, the less of the nonspecific element will be 

 retained. This is probably the reason that the more modern serums 

 have at times seemed followed by less therapeutic effect than the for- 

 mer preparations. As a matter of fact when some of the older litera- 

 ture is reviewed one finds observations concerning the temporary rise 

 in temperature following diphtheria antitoxin injections, as well as 

 the temporary leukopenia and the later leukocytosis that we now 

 recognize as part of the phenomena that follow after the various 

 nonspecific injections (Ewing). 



A number of investigators have repeated BingePs method, using 

 the method of toxin neutralization in guinea pigs. Calhoun, for in- 

 stance, as well as Kraus and Sordelli, found a slight protection with 

 normal horse serum; other observers have found little or no protec- 

 tion. The lack of confirmation in animal work does not, however, 

 rule out a therapeutic effect in human diphtheria. Liidke has for 

 instance treated 15 cases of diphtheria in adults with albumoses. (2-3 

 injections of from 3-5 c.c. of a 10% solution.) The therapeutic effects 

 were quite comparable to those obtained with specific serum therapy. 

 In 7 cases the first injection was followed by a complete disappearance 

 of the diphtheritic membrane and the return of the temperature curve 

 to normal within 24 hours. In three cases in which a stenosis already 



