388 EXAMPLES OF CHEMICAL CORRELATION 



proved possible to induce tetany by injections of ammonia or ammo- 

 nium carbonate. 



The urine of children between the ages of two and fifteen normally 

 contains Creatine, which is absent from the urine of adults, 1 and it is 

 between these ages that children are most liable to develop symptoms 

 of tetany. On the other hand the content of creatine in muscular 

 tissues is definitely connected with their Tonus or degree of tonic 

 contraction and is increased by all measures which increase tonus. It 

 has therefore been suggested by many observers that the tetany arising 

 from parathyroidectomy may originate in a disturbance of the normal 

 metabolism of creatine. In this connection it is of especial interest 

 to note that Landois and Maxwell have found that while the gray 

 matter of the motor-areas of the cerebral cortex is remarkably insensi- 

 tive to the ordinary chemical stimuli which increase the irritability of 

 nerve-fibers (calcium precipitants), it is powerfully stimulated by 

 applications of creatine, with the effect of inducing convulsions. It has 

 not, however, proved possible to induce tetany in animals by injections 

 of creatine. 



Creatine is methyl guanidine acetic acid, and is therefore related to 

 the amino-acid, Arginine, the relationship of arginine, methyl guanidine 

 and creatine to one another is shown by the following formulae: 



/CH 3 



,NH.CH 2 .CH 2 .CH 2 .CH.NH 2 COOH /NH.CHs N CH 2 COOH 



C=NH C=NH C=NH 



\ 



S NH 2 \NH 2 ^NHz 



Arginine. Methyl guanidine. Creatine. 



Methylguanidine and Dimethyl Guanidine occur in small amounts in 

 blood, muscular tissues 'and urine. It has recently been shown by N. 

 Paton that the quantity of methylguanidine in the blood and urine is 

 decidedly increased after parathyroidectomy in animals, and in the 

 spontaneous tetany which occurs in children. The following figures are 

 illustrative: 



Guanidine + Methylguanidine in milligrams per liter. 



A. BLOOD. 

 DOGS. 



Normal Parathyroidectorny. 



. 1 . 00 (average of 5) 8.7 (average of 8) 



B. UBINE. 

 DOGS. 



Nor mal. Parathyroidectomy. 



LO. 25 (average of 6) 1.1 (average of 6) 



CHILDREN. 



Idiopathic tetany. 

 0.12 (average of 8) (Average of 3 cases) 



Active tetany . . . . 0.58 

 Latent tetany . . . . 0.38 

 Recovery . . . . . 0.12 



1 Occasionally present in the urine of women. 





