254 Studies in Metabolism. I 
and methyl guanidine, exert a hyperexcitability on the nerves. Methyl 
guanidine was first isolated from normal human urine as the aurochloride 
by Kutscher and Lohmann (8) in 1906 and later by Engeland (9). Achelis 
(10) isolated it from normal dog urine as the picrolonate. The quantities 
found by the above three investigators correspond to about 0.007 gm. of 
the gold salt per liter. Koch (11) detected methyl guanidine in the urine 
of a dog which had been subjected to parathyroidectomy. In this case 
as much as 1.9 gm. per liter of the gold salt of the drug were found. In 
his second paper (12) he described more fully the occurrence of methyl 
guanidine and some of the other toxic bases in the urine in five parathy- 
roidectomized dogs and stated that in all cases that he studied he found 
methyl guanidine. In those cases in which the quantity of methyl guani- 
dine was small, other guanidine bases were present so that he considered 
the quantity of guanidine nitrogen to be constant in all cases. Burns 
and Sharpe (13), using more satisfactory methods than former workers, 
carefully determined the guanidine and methyl guanidine in the blood 
and urine of dogs after parathyroidectomy and reported a marked in- 
crease. They found an increased content of guanidine and methyl guan- 
idine in the urine of children suffering from idiopathic tetany. They com- 
pared normal and abnormal dogs and showed an increase in guanidine of 
90 per cent in blood and 40 per cent in the urine after parathyroidectomy. 
In the urine of children in condition of active tetany there was an increase 
of 500 per cent per liter over the normal. Such an increase of a spasmodic 
agent as guanidine suggests the cause of the development of the symptoms 
of tetany. 
Paton and Findlay (7) demonstrated with careful observation on rab- 
bits that the symptoms of tetania parathyreopriva are identical with 
those produced by the administration of the salts of guanidine and methyl 
guanidine. 
In addition to the above workers, Underhill and others published a 
series of papers on carbohydrate metabolism in thyreoparathyroidecto- 
mized dogs. Hirsch (14), Eppinger, Falta, and Rudinger (15), and Pari 
(16) demonstrated that the assimilation limit for dextrose given by mouth 
or subcutaneously is lowered in thyreoparathyroidectomized dogs. Un- 
derhill and Saiki (17) also reported that thyreoparathyroidectomized dogs 
are incapable of utilizing subeutaneously introduced dextrose. They 
show a lessened oxidation or glycolysis and also a decreased ability to 
transform dextrose into glycogen. Underhill and Hilditch (18) observed 
that when the thyroids and all the parathyroids attached are removed 
from dogs, the ability to assimilate sugar is decreased. When the thyroid 
alone is extirpated this ability is not impaired. They consider that the 
thyroid-parathyroid mechanism stands in intimate connection with car- , 
bohydrate metabolism and that the parathyroids are the more active agents 
in this connection. Underhill and Blatherwick (19) found that during 
the tetany after thyreoparathyroidectomy, glycogen entirely disappeared 
from the liver and that the blood sugar content was markedly lowered. 
They attribute this phenomenon to the lack of parathyroid tissue since 
