An3J?";m?nn'}    Standardization  of  Digitalis  Bodies.  in 
In  none  of  the  methods  is  it  suggested  that  immature  animals 
may  be  used  along  with  mature  ones,  and  one  of  Eckler's  cats 
which  showed  marked  abnormality  of  reaction  was  obviously  a 
kitten,  weighing  only  970  grams.  One  of  the  first  observations 
made  by  Hatcher  on  the  factors  which  may  enter  to  cause  variations 
in  the  response  of  cats  was  the  effect  of  an  overabundance  of  fat  (1) 
and  this  probably  accounts  for  another  of  the  great  variations 
observed  by  Eckler,  for  one  animal  weighed  4.7  kg. 
It  is  stated  that  frogs  coming  from  different  localities,  although 
of  the  same  species,  show  differences  in  reaction  to  the  same  prepa- 
ration. Such  does  not  seem  to  be  the  case  with  cats.  We  have 
established  the  cat  unit  for  ouabain  as  0.1  mg.  per  kg.  and  Eckler's 
table  of  26  tests  gives  an  average  of  0.095  mS-  kg.  A  series 
of  eight  cats  sent  to  us  from  Ithaca  gave  0.093  m£-  as  the  unit. 
The  fourth  important  requirement  is  that  the  method  of  stand- 
ardization shall  have  a  wide  range  of  applicability,  that  is,  it  should 
be  possible  to  use  it  for  the  evaluation  of  pure  principles,  galenical 
preparations,  proprietaries,  and  unknown  solutions  containing  one 
or  more  of  the  members  of  the  digitalis  group. 
Both  the  guineapig  and  frog  methods  fail  in  greater  or  less 
degree  to  provide  for  such  contingencies.  In  both  the  element  of 
absorption  is  an  essential  factor  and  is  the  chief  element  which 
limits  the  range  of  applicability  of  these  methods.  Specimens  which 
contain  relatively  large  amounts  of  colloidal  material  would  probably 
be  found  to  give  values  considerably  too  low  by  the  guineapig 
method,  as  colloids  are  well  known  to  exert  a  marked  inhibitory 
action  upon  absorption  from  the  subcutaneous  tissues.  In  the  case 
of  the  frog  methods  this  element  of  absorption  is  well  illustrated 
by  our  utter  inability  to  establish  any  fatal  dose  for  liquid  digalen 
by  the  one  hour  tests.  Hale's  determination  which  shows  crystal- 
line digitoxin  to  be,  "  eight  times  less  active  than  amorphous 
strophanthin "  is  another  illustration  of  the  effect  of  absorption. 
Certainly  no  one  believes  that  this  ratio  is  in  any  way  proportional 
to  the  relative  activity  of  the  two  drugs  for  man  or  the  higher 
animals. 
High  alcoholic  content  of  the  preparation  renders  it  necessary 
to  evaporate  off  the  alcohol,  at  least  in  part,  and  make  up  the  solution 
with  saline  for  testing  by  the  frog  method,  and  the  same  process  is 
followed  by  Reed  and  Vanderkleed  in  their  tests  of  tinctures  on 
guineapigs,  although  they  state  that  the  guineapig  is  very  resistant 
to  alcohol.    The  introduction  of  heat  and  the  change  of  solvent  are 
