322 RETROGRESSIVE CHANGES 



although fresh pancreatic juice caused fat necrosis, a commercial 

 preparation of trypsin did not do so, and, therefore, he con- 

 cluded that probably the lipase of the pancreatic juice was the 

 active agent. Flexner 1 supported this contention by demon- 

 strating the presence of a fat-splitting enzyme in foci of fat 

 necrosis, which was corroborated by Opie. 2 The latter 3 was also 

 able to demonstrate the presence of lipase in the urine of a 

 patient with fat necrosis. 4 



In a study of the pathogenesis of fat necrosis, particularly 

 with reference to the question whether the lipase or the trypsin 

 of the pancreatic juice was responsible, Wells 5 found that typi- 

 cal fat necrosis could be produced by injecting extracts of fresh 

 pancreas into animals, either of the same species as that from 

 which the pancreas was obtained, or into a foreign species. 

 Commercial " pancreatins " were also quite effective, whether 

 in weak acetic acid or weak alkaline solutions. The power of 

 these materials to cause fat necrosis was reduced by heating to 

 or above 60 for five minutes, and completely destroyed at 71, 

 indicating that the active agent is an enzyme. But, as in the 

 same material trypsin was injured by temperatures above 60, 

 and destroyed at between 70 and 72, and lipase was weakened 

 above 50, and destroyed above 70, it was impossible to deter- 

 mine, by heating pancreatic preparations, whether the lipase or 

 the trypsin was the essential factor. By permitting pancreatic 

 extracts to digest themselves it was found that the power to 

 produce fat necrosis decreased, pari passu, with the decrease in 

 lipolytic strength. Preparations strongly tryptic, but very 

 weak in lipase, produced no fat necrosis, and, on the other 

 hand, extracts of pig's liver or of cat's serum, both rich in 

 lipase but devoid of trypsin, were equally ineffective. Fur- 

 thermore, mixtures of liver or serum lipase and trypsin were 

 incapable of causing fat necrosis. Fresh pancreatic extracts 

 from fasting dogs, containing lipase but almost no trypsin 

 (which in fresh extracts is still in the form of inactive trypsin- 

 ogen), produced abundant fat necrosis, whereas after the tryp- 

 sinogen in such extracts was activated by enterokinase, no fat 



1 Jour. Exper. Med., 1897 (2), 413. 



2 Contrib. of pupils of W. H. Welch, Baltimore, 1900, p. 859 : Johns Hopkins 

 Hosp. Kep., 1900 (9), 859. 



3 Opie, " Diseases of the Pancreas," Lippincott 1903, p. 156 ; Johns Hopkins 

 Hosp. Bull., 1902 (13), 117. 



* It yet remains to be seen if this is a constant occurrence ; and also if the 

 lipase so excreted comes from the pancreas, forZeri (II Policlinico, 1905 (12), 

 733 has found lipase in the urine in hemorrhagic nephritis and inflammation 

 of the urinary tract. 



5 Jour. Med. Research, 1903 (9), 70. 



