C. L. HOAGLAND 



mens was rendered normal by the in vitro addition of a-tocopherol 

 phosphate (9). 



Notwithstanding the fact that progressive muscular dystrophy 

 has engaged the interest of clinicians since the original description of 

 the syndrome in the middle of the 19th century, almost no attempts 

 were made to study the general metabolism in this disease until the 

 pioneer work of Levene and Kristeller (11) in 1909. These workers 

 showed that the feeding of protein resulted in an excessive excretion 

 of creatine in patients with progressive muscular dystrophy. Subse- 

 quently, many studies have revealed that there is marked derangement 

 in metabolism of creatine in this disease, and that endogenous creatine, 

 formed from protein and amino acids, is not retained by the muscles 

 as effectively as in normal subjects. This observation has given rise 

 to the concept that there is, in progressive muscular dystrophy, a 

 diabetic-like state with respect to the ability of the patient to retain 

 either ingested creatine or creatine which is formed endogenously 

 from proteins and amino acids. Whether or not this is a true concept, 

 the recognition of a biochemical aberration in creatine metabolism is 

 perhaps the only truly significant contribution to have been made 

 within the last thirty years toward an understanding of the essential 

 nature of this disease. 



Of perhaps even greater significance than an increase in excre- 

 tion of creatine in progressive muscular dystrophy is a diminished out- 

 put of creatinine. Because of the specific association of creatinine 

 formation with the integrity of muscle processes, the urinary concen- 

 tration of this material may, in certain cases, give a more reliable indi- 

 cation of the severity of the disease than the level of urinary creatine (7). 

 Moreover, the relatively great constancy in the excretion of creatinine, 

 even under widely diff'ering conditions of diet and health of the sub- 

 ject, permits the attachment of greater significance to small changes in 

 the urinary concentration of this material than is the case with crea- 

 tine, which may show wide fluctuations from day to day. The fact 

 that creatinine is not derived from all tissues, but that it arises as a 

 special process of tissue catabolism taking place "largely if not wholly 

 in the muscles," has given rise to the belief that the amount of creatinine 

 excreted in the urine "bears a direct relation to the potential elficiency 

 of the muscles and is a reliable index of the muscular development of 

 an individual" (15). The belief, originally stated by Foiin, that 



420 



