778 Colchicine 



spindle destruction. These changes ^vere considered at the time as 

 evidence ot mitotic stimulation by colchicine (ci. Chapter 9) ; they 

 are probably only an indirect effect, the alkaloid having destroyed 

 hepatic cells and later arrested the mitoses needed lor regeneration. 



One other similar pathological description has recently been 

 published. ^^ This was a case of acute poisoning. A five-year-old girl 

 swallowed an inikn()\vn number of seeds. These were later identified 

 as belonging to the genus Colchi( inn. Repeated ^omiting and ab- 

 dominal pain were the first signs of toxicity. The central temjierature 

 rose and the pulse became fast. Death followed in 38 hours. Cerebral 

 edema was conspicuous. Small hemorrhagic dots were seen on the peri- 

 cardium and the peritoneal serosa. The duodenal mucosa was swollen 

 and dotted with man\ hemorrhagic zones. 



Evidence of mitotic poisoning was visible in the li\er, where some 

 cells were in a condition of arrested metaphase. Others showed evi- 

 dence of degenerati\e alterations. Arrested metaphases were con- 

 spicuous in the bone marrow; a small number could be foimd in the 

 duodenal mucosa. Pycnotic destruction of lymphocytes in lymph 

 glands, Peyers patches, and the thymic cortex was probably the result 

 of the combined action of the mitotic poison and of the general alarm- 

 reaction."" 



Colchicine was detected b\ a biological method, while chemical re- 

 actions remained negative. Large quantities were found in se\eral 

 organs, in particular the liver, the kidney, and the brain. Extracts 

 from these tissues displaced a typical spindle-poisoning effect when 

 brought into contact with chick fibroblast cultures. 



In the complex changes which take place when a large dose of 

 colchicine is absorbed in man, it is evident that some are related to 

 the poisoning of cell division, for instance bone-marrow inhibition. '■'■ ^^ 

 while others, such as the destruction and regeneration of liver cells, 

 and the evidence of stress, are of a more complex nature. Vomiting, 

 which may appear shortly after the drug is taken, is one major sign 

 of a series of disturbances which clearly have nothing to do with the 

 cytological effects which have been studied so far. These will now be 

 described from data on various mammals and \crtebrates, before 

 analyzing the changes possibly related to spindle inhibition. The 

 important problem of the metabolism of colchicine in the bodv will 

 be discussed in a later paragrajjh. 



7.3: Disturbances Unrelated to Mitotic Poisoning 



Vomiting, diarrhea, bloody stools, and a progressive paralysis of 

 the central nervous system are the most evident signs of toxicity. Death 

 occurs within several hours in warm-blooded animals, or several davs in 

 cold-blooded \ertebrates. after injections of the largest doses. In 1906, 



