NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
16
(b) Quinine by the month.
Rabbits and guinea pigs can survive larger doses introduced into the stomach
than hypodermically. In the case of rabbits the lethal dose by the stomach would
at least be double the hypodermic lethal dose, but in the case of guinea pigs a
lethal dose would prove fatal when increased by 1/5to¼ its amount and given by
the stomach. (See Tables V and VI.)
In guinea pigs the symptoms produced resemble those following hypodermic
injections, and set in with the same rapidity, but are not quite so severe unless very
large doses are given ; whereas in rabbits the symptoms are hardly noticeable,
except when large doses are given, when they lie down on their stomachs, stretch
out their legs, and respire with difficulty.
The results of the experiments recorded on Tables IV and V indicate a marked
difference between the lethal doses for a rabbit hypodermically and by the stomach.
Twelve grains is a certain lethal dose for a 2,000 gramme rabbit when given hypo-
dermically, but a rabbit of the same weight can survive 25 grains when given by
the stomach. Compared with rabbits, the difference in guinea pigs is only slight.
A 500 gramme guinea pig can survive 4 grains by the stomach, when 3½ grains
given hypodermically kills an animal of the same weight.
Evidently weight for weight these small animals are far more tolerant of
quinine than man.
A guinea pig which, roughly speaking, weighs only lib. (500 grammes) can
survive 4 grains by the stomach, and. if man, weight for weight, could withstand
the same amount, this would mean that a man weighing 11 stone could survive a
dose of 616 grs. of quinine by the stomach, which is impossible ; even a quarter of
this amount would almost be a poisonous dose for a man.
(c) Quinine intravenously.
The intravenous method of giving quinine was tested on rabbits only. In
these animals a small dose given into a vein kills quickly. One grain in 1 c.c. normal
saline solution will in 9 cases out of 10 kill a rabbit weighing from 1,700 to 2,000
grammes, and any slight increase in this amount would prove fatal within one
minute.
0.5 grain of quinine per kilogramme represents about the lethal dose for a
rabbit when given intravenously.
Rabbits weighing from 1,200 to 1,500 grammes can bear ½g r a i n d i s s o l v e d i n
½ c.c.. normal saline solution, without showing any very noticeable symptoms.
When large doses such as 0.75 grains per kilo. are given, the animals commence to
die immediately the injection is completed, and in most cases they are dead within
one minute. Respiration suddenly ceases, but the heart goes on beating for some
minutes.
17
A more dilute solution of the quinine salt and a proportional diminution of its
acidity makes no difference in its killing properties. (See the experiments detailed
in Table VII and compare experiments 4 and 6 with 7 and 8.)
From this fact one would infer that the lethal effects are due to the quinine
and not to the acidity of the solution.
In order to make this point certain, the series of experiments detailed in Table
VII were devised. As I have already mentioned, the quinine was used in the pro-
portion of 1 grain to 1 c.c. normal saline solution, and the acidity of a solution
of this strength corresponds to 1.3 per cent. H2 SO4, or 1 per cent. H.Cl.
Rabbits weighing from 1,400 to 1,500 grammes can withstand intravenously
1 c.c. of normal saline solution containing either of these mineral acids in the per-
centages given (1.3 per cent. H2 SO4 or 1 per cent. H.Cl.) They can also with-
stand 2 c.c. of normal saline solution containing 1½ per cent. of either acid and
show no symptoms of any kind, and this is an acidity much stronger and in a
larger bulk of fluid than the lethal quinine dose in a dilution of 1 grain in 1 c.c.
Stronger dilutions of H2 SO4, such as 1½ c.c. of a 5 per cent. dilution kill very
quickly, but the same amount of 5 per cent. dilution of H.Cl. gives rise to no ap-
parent symptoms. (See the experiments detailed in Table VIII.)
Any blood changes which may occur after the intravenous injection of quinine
in rabbits are not apparent when rapidly fatal doses are given, but when several
non-lethal doses are given traces of hæmolysis are to be found in the supernatent
fluid after centrifuging a sample of blood with an equal volume of 1½ per cent.
citrate of soda in normal saline solution ; when another sample is taken and
allowed to clot, clotting takes place as usual, and the serum is tinged red.
Stained specimens appear normal, and leucocytes are present in the propor-
tion found in normal rabbits.
W h e n ½ g r a i n d o s e s a r e g i v e n i n t r a v e n o u s l y e v e r y 1 0 m i n u t e s , s y m p t o m s o f
quinine poisoning set in after the second dose and become more pronounced
after every subsequent dose, and the animal dies asphyxiated after the eighth or
ninth dose. In an experiment of this kind (No. 11, Table VII) there were no
apparent blood changes after the sixth and seventh doses, but 30 minutes after
the ninth dose, the animal died, and evidence of hæmolysis was apparent in speci-
mens taken from the heart immediately after death. The blood clotted like a
normal specimen, but the serum was tinged red, and so was the supernatent fluid
of another specimen after centrifuging with an equal volume of 1½ per cent. of
citrate of soda in normal saline solution, specimens taken at the same time and
stained appeared normal. See Table VII for results of intravenous injection.
When large hypodermic doses are given to rabbits, traces of hæmolysis will be
found after a few hours, should the animals survive for so long ; and in those that
succumb similar changes will be found immediately after death, but nothing abnor-
D 2
18
mal appears in stained specimens. See Table IX for blood changes after large
hypodermic doses.
Is there any tolerance to large doses of quinine ?
A non-lethal doss of quinine given hypodermically to a rabbit one day, does
not establish any tolerance to what would, in the ordinary course of events, prove a
lethal dose given the next day. When the interval between the first and second
doses is extended to a fortnight a similar absence of any tolerance is evident. (See
Table IX.)
Table I.
Experiments on Guinea Pigs to test the effects of Quinine when dissolved in normal
saline solution and given hypodermically.
No. of
experi-
ment.
Weight
of guinea
pig.
Salt of
quinine
used.
Amount
given.
Quantity
of normal
saline in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1
500
Bihy-
drochlo-
ride.
3
3
Muscular spasms after 10
minutes, severe and con-
tinued for several hours.
Appeared well next day.
Died after
9 days.
Skin and tissues
sloughed at seat
of injection.
2
500
Ditto.
5
5
Severe muscular spasms
after 7 minutes.
Died after
4 hours.
Escharotic action
on tisses at seat of
injection.
3
500
Ditto.
3
3
Muscular spasms after 8
minutes; looked like dying
after 5 hours ; began to im-
prove after 6 hours ;
seemed well next day.
Died after
38 days.
General wasting.
4
500
Ditto.
3
3
Ditto ditto
. Died after
36 days.
Ditto ditto.
5
500
Ditto.
3½
3½
Muscular spasms after 15
minutes. Lay helpless in
cage with twitching of
muscles after 6 hours.
Died after
9 hours.
Escharotic action
on tissues at seat
of injection.
6
320
Ditto.
3
3
Muscular spasms after 7
minutes.
Died after
4 hours.
Ditto ditto.
7
350
Ditto.
2
3
Muscular spasms after 10
minutes.
Died after
17 hours.
Ditto ditto.
8
300
Ditto.
2½
2½
Ditto ditto
. Died after
14 hours.
Ditto ditto.
9
390
Ditto.
1
1
Muscular twitching and ex-
cited after 10 minutes.
Apparently well after 2
hours.
Survived . Oedema and ten-
derness at seat of
injection.
10
350
Ditto.
1
1
Ditto ditto
.
Ditto . Skin and tissues
sloughed at seat
of injection.
19
Table I—contd.
Experiments on Guinea Pigs to test the effects of Quinine when dissolved in normal
saline solution and given hypodermically— contd.
No. of
experi
ment.
Weight
of guinea
pig.
Salt of
quinine
used.
Amount
given.
Quantity
of normal
saline in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
11
350 Bihy
drochlo
ride.
1½
1 ½
Convulsions after 10
minutes, severe for 3 hours.
Died after
20 hours.
Marked escharotic
action on tissues
at seat of injec
tion.
12
300 Ditto.
2
2
Ditto
ditto
Died after
3¼ hours.
Ditto ditto.
13
350 Ditto.
1
½ Muscular twitching after 10
minutes.
Survived Skin and tissues
sloughed at seat
of injection.
14
350 Ditto.
1½
¾ Convulsions after 10
minutes; severe for 4 hours.
Survived . Local sloughing.
15
350 Ditto.
2
1
Severe convulsions after 10
minutes.
Died after
24 hours.
Severe escharotic
action at seat of
injection.
It is evident from this series of experiments that 1 grain of quinine bihydrochoride per 150 grammes of
guinea pig is a certain lethal dose when given hypodermically; and in some cases a smaller amount would suffice.
Table II.
Experiments on Guinea Pigs to test the effects of Quinine when dissolved in normal saline
solution and given hypodermically.
No. of
experi
ment.
Weight
of guinea
pig.
Salt of
quinine
used.
Amount
given.
Quantity
of normal
saline in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1
500 Bihy
drochlo
rate.
4
4
Severe muscular spasms
after 10 minutes, tetanic
in character and continued
for hours; seemed well
next day except for pain
and thickening at the seat
of injection.
Died after
4 days.
Sloughing took
place at seat of
injection.
2
350 Ditto.
5
5
Muscular spasms after
8 minutes. Severe in charac
ter and lasting until death.
Died after
7 hours.
Tissues at seat of
injection necrosed.
3
340 Ditto.
2
2
Muscular spasms after 10
minutes, severe in charac
ter.
Died after
2 days.
Ditto ditto.
4
440 Ditto .
1
1
Excited after 10 minutes,
no spasms.
Survived . Ditto ditto.
It will be seen that the results recorded in this table in which bihydrochlorate of quinine was used, differ in
no material point from those in which the bihydrochoride was used.
20
Table III.
Experiments on Guinea Pigs to test the effects of quinine when dissolved in normal saline
solution and given intramuscularly.
No. of
experi
ment.
Weight
of guinea
pig.
Salt of
quinin
e used.
Amount
given.
Quantity
of normal
saline in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1
440 Bihy
drochlo
ride.
3
3
Severe muscular spasms
after 10 minutes.
Died after
24 hours.
Marked swelling in
muscles of thigh at
seat of injection,
and gelatinous ex
udation.
2
430 Ditto.
2
2
Muscular spasms after 8
minutes.
Died after
16 hours.
Ditto ditto.
3
400 Ditto.
1
1
Muscular twitchings after
8 minutes. Seemed well
next day.
Survived. Pain and swelling in
muscles of thigh at
seat of injection
for several days, a
sloughing sore on
the 5th day.
The general effects after intramuscular injections resemble those produced by hypodermic injections, and
set in with the same rapidity.
Table IV.
Experiments on Rabbits to test the effects of Quinine when dissolved in normal saline
solution and given hypodermically.
No. of
experi
meat.
Weight
of
rabbit.
Salt of
quinine
used.
Amount
given.
Quantity
of normal
saline in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1 1,320 Bihy
drochlo
ride.
3
3
Refused its food for a day ;
no other symptom.
Survived . Local tenderness
and thickening at
seat of injection.
2 1,400 Ditto.
5
5
Ditto ditto .
. Ditto . Ditto ditto.
3 1,410 Ditto.
10
10
Quickened respiration com
menced 10 minutes after
dosé. Lay helpless in
cage after one hour.
Died after
4 hours.
Escarotic action
at seat of injec
tion.
4 1,500 Ditto.
10
10
Quickened respiration after
10 minutes, then lay help
less in cage.
Died after
30 minutes.
Ditto ditto.
5 1,500 Ditto.
8
8
Excited after 10 minutes,
quickened respiration after
30 minutes.
Died after
2½ hours.
Ditto ditto.
6 1,500 Ditto.
6
6
Excited after 30 minutes ;
apparently well After 2
hours.
Survived . Slough at seat of
injection.
Six grains per kilogramme of rabbit is a certain lethal dose, but in some cases less would suffice.
21
Table V.
Experiments on Rabbits to test the effects of Quinine when dissolved in normal saline
solution and given by the stomach.
No. of
experi-
ment.
Weight
of
rabbit.
Salt of
quinine
used.
Amount
given.
Quantity
of normal
saline in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1
2,060
Bihy-
drochlo-
ride.
30
30
After 20 minutes lay down
in cage, and breathing
difficult. Apparently well
one hour after dose.
Died after
12 hours.
Sloughy patch of
mucous membrane
near duodenal end
of stomach expos-
ing a local sub-
mucous hæmorrhage.
2
2,050
Ditto.
15
15
After 20 minutes, quickened
respiration. Seemed well
after one hour.
Survived.
3
2,000
Ditto.
20
20
Ditto ditto
.
.
Ditto . After three weeks
wasting set in and
death took place at
the end of a month.
P. M. disclosed no
apparent disease.
4
2,000
Ditto .
25
25
Ditto ditto
.
.
Ditto .
15 grains per kilogramme of rabbit is a certain lethal dose when given by the stomach; less would suffice in
some cases.
Table VI.
Experiments on Guinea Pigs to test the effects of Quinine when dissolved in normal saline
solution and given by the stomach.
No. of
experi-
ment.
Weight
of guinea
pig.
Salt of
quinine
used.
Amount
given.
Quantity
of normal
saline in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1
470
Bihy-
drochlo-
ride.
3
5
Slight spasms on handling
after 2½ hours, but these
soon disappeared. Pro-
gressive emaciation set in
after the 2nd day.
Died after
10 days.
General wasting.
2
500
Ditto.
5
5
Severe spasms after 10
minutes (convulsions).
Died after
4½ hours.
Stomach normal.
3
500
Ditto .
4
4
Excited after 20 minutes,
slight spasms after 1 hour.
Seemed well after 3 hours.
Survived.
4
500
Ditto.
3
3
Excited after ¾ hour.
Seemed well after 2 hours.
Ditto.
1¼ grs. per 150 grammes of guinea pig is a certain lethal dose when given by the stomach; but in some cases
less would suffice.
22
Table VII.
Experiments on Rabbits to test the effects of Quinine when dissolved in normal saline
solution and given intravenously.
No of
experi-
ment.
Weight
of
rabbit.
Salt of
quinine
used.
Amount
given.
Amount
of fluid in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1
1,300
Bihy-
drochlo-
ride.
3
3
Respiration suddenly
ceased.
Died with-
in one
minute.
P. M. immediately
after death. Blood
appeared normal.
No clots in heart
or large vessels.
No hæmolysis.
Stained specimens of
blood normal.
2
1,400
Ditto.
2½
2 ½
Ditto ditto .
.
Ditto .
Ditto ditto.
3
1,990
Ditto.
2
2
Ditto ditto .
.
Ditto .
Ditto ditto.
4
1,740
Ditto.
1
1
Ditto ditto .
.
Ditto
.
Ditto ditto.
5
1,970
Ditto.
½
½ Slight difficulty in breathing
for a few minutes after in-
jection. Seemed well after
15 minutes.
Survived A capsule of blood
gave norma1
coloured serum on
clotting. A stained
specimen of blood
appeared normal.
No hæmoloisis.
6
1,760
Ditto.
1
1
After a minute it rolled over
and struggled for breath
and looked like dying; be-
gan to recover after 5
minutes but breathed
rapidly for 20 minutes;
seemed well after 30
minutes.
Recovered Tested blood 5 hours
after quinine.
Stained specimen
normal. Clotting
and serum normal.
Traces of hæmolysis
on centrifuging with
citrate of soda
solution.
7
1,750
Ditto.
1
2
Slight difficulty of respira-
tion for a minute after in-
jection but no other symp-
tom.
Ditto . Blood same as ex-
periment 6.
8
1,570
Ditto.
1
2
Respiration suddenly
ceased.
Died with-
in one
minute.
P. M. immediately
after death. No
clots in heart or
large vessels. Blood
normal in appear-
ance. Stained spe-
cimens normal.
Clotted normally.
No hæmolysis.
9
2,170
Ditto.
2
6
Struggled for breath for 30
seconds, then breathing
suddenly ceased.
Died with-
in one
minute.
P. M. and condition
of blood same as
experiment 8.
10
1,450
Ditto.
2 ½
1 ½
given in
½ c . c .
doses
(½ gr.) at
intervals
of 5
minutes.
Slight difficulty of breathing
for a minute or two after
each injection; otherwise
no symptoms.
Survived A capsule of blood
gave normal colour-
ed serum on clot-
ting. A stained
specimen of blood
appeared normal.
No hæmolysis.
23
Table VII — contd.
Experiments on Rabbits to test the effects of Quinine when dissolved in normal
saline solution and given intravenously —contd.
No. of
experi-
ment.
Weight
of
rabbit.
Salt of
quinine
used.
Amount
given.
Amount of
fluid in
which
dissolved.
Symptoms produced.
Result.
REMARKS.
grms.
grs.
c.c.
1 1
1,760
Bihy
drochlo-
ride.
4½
4½ c.c.
given in
½ gr.
doses
every 10
minutes.
None after first dose, but
respiration quickened, and
marked respiratory diffi-
culty after all the other
doses, and lasting from 5
to 8 minutes. These
symptoms increased after
the 9th dose (last dose),
and continued for 30
minutes, when death sud-
denly took place.
Died 30
minutes
after last
dose.
Blood tested after
the 6th and 7th
doses appeared nor-
mal, as regards
clotting, serum and
stained specimens.
No hæmolysis.
P. M. immediately
after death. No
clots in heart or
large vessels, and
blood normal in
appearance and in
stained specimens.
A sample taken in a
glass capsule clotted
in the usual time,
but serum slightly
tinged red (hæmo-
lysis). On centri-
fuging a small
quantity in 1½ per
cent. citrate of soda
in normal saline,
the supernatent fluid
was slightly tinged
red, showing evi-
dence of hæmolysis.
¾ gr. per kilogramme of rabbit is a certain lethal dose when given intravenously; but in some cases less
would suffice.
Table VIII.
Experiments on Rabbits to test the effects of Sulphuric or Hydrochloric Acid when
given intravenously.
No. of
experiment.
Weight of
rabbit.
Dilution of
sulphuric or
hydrochloric
acid in nor-
mal saline
solution.
Amount given.
Symptoms pro
duced
Result.
REMARKS.
grms.
c.c.
1 . S u l p h u r i c
acid.
1,450
5 per cent.
1½ into vein of
ear.
Breathing sud-
denly ceased.
Died within P.M. immediately
one minute. after death. Blood
in jugular vein lead-
ing from ear-vein
injected was thick,
black, and tarry
looking. Heart's
blood was dark
and contained some
loose dark clots.
24
Table VIII—contd.
Experiments on Rabbits to test the effects of Sulphuric or Hydrochloric Acid when
given intravenously —contd.
No. of
experiment.
Weight of
rabbit.
Dilution of
sulphuric or
hydrochloric
acid in nor-
mal saline
solution.
Amount given
Symptoms pro-
duced.
Results.
REMARKS.
2. Sulphuric
acid.
1,420
2½ per cent. 1½ c.c. into
vein of ear.
Difficulty of re-
spiration for a
minute or so ;
no other symp-
tom.
Remained
well.
3. Ditto
.
1,350
1½ per cent. 2 ditto .
Nil .
.
Ditto.
4. Hydrochloric
acid.
1,390
5 per cent. 1½ ditto .
Nil .
.
Ditto.
5. Ditto
.
1,410
5 per cent.
2 ditto
Nil .
.
Ditto.
6. Ditto
.
1,550
1½ per cent. 2 ditto .
Nil .
.
Ditto.
This table proves that the results of the intravenous injections of quinine recorded in Table VII were due to the
quinine, and not to the acidity of the dilution ; because, when quinine bihydrochloride is dissolved in normal
saline solution in the proprotion of 1 gr. to 1 c.c. the acidity as represented by the amount of combined
acid is equal to 1.3 per cent. H 2 SO4, or 1 per cent. H. Cl.
It is evident that H2 SO4 is more poisonous for rabbits when given intravenously than H.Cl. 1½ c.c. of a 5 per
cent. H2 S O
4 k i l l e d a 1 , 4 5 0 g r a m m e s r a b b i t w i t h i n 1 m i n u t e , w h e r e a s 1 ½ c . c . a n d 2 c . c . o f a 5 . p e r c e n t . H . C l .
produced no symptoms in rabbits weighing 1,390 and 1,410 grammes respectively. See experiments 1 and 4
and 5.
Table IX.
Experiments on Rabbits to prove whether a non-lethal dose of Quinine given one day
would establish a tolerance to a lethal dose given the next day, or at a later
period.
No. of
experi-
m e n t .
Weight
of
rabbit.
Salt of quinine
used.
Amount given
and dates.
Quantity of
normal sal-
ine in which
dissolved.
Symptoms produced. Result.
REMARKS.
grms.
grs.
c.c.
1
1,840 Bihydrochloride 24th August 7 17
No apparent symp-
toms.
Not ill after
1st dose.
Ditto
. 25th August 12
12
Very quickened
breathing after 15
minutes.
Died ¾ hours
after 2nd
dose.
P. M. immediately
after death.
Heart continued to
beat several min-
utes after death.
Blood apparently
normal, no clots
in heart or large
vessels. Traces
of hæmolysis on
centrifuging a
specimen of blood
in 1½ per cent.
citrate of soda
in normal saline
solution.
25
Table IX—contd.
Experiments on Rabbits to prove whether a non-lethal dose of Quinine given one day
would establish a tolerance to a lethal dose given the next day, or at, a later
period—contd.
No. of.
experi-
ment.
Weight
of
rabbit
Salt of quinine
used.
Amount given
and dates.
Quantity of
normal sal-
ine in w ich
dissolved.
Symptoms pro-
duced.
Result.
REMARKS.
grs.
c.c.
2 .
.
1,870 Bihydrochloride 24th August 9
9
Respiration quick-
ened after one
hour ; apparently
well after 2 hours.
Well 2 hours
after 1st dose.
Ditto
. 25th August 12
12
Rapid breathing
after 10 minutes.
Died 1½ hours
after 2nd
dose.
P. M. immediately
after death. Same
condition found
as in No. 1.
3 .
.
1,650
Ditto
. 11th August 6
6
Excited after 20 min-
utes. Seemed well
after 1 hour.
Well 1 hour
after 1st dose.
Ditto
. 26th August 10
10
Rapid respiration
after 40 minutes ;
very ill after 2
hours ; seemed dy-
ing after 5 hours ;
began to improve
after 6 hours.
Recovered
from the
effects of
2nd dose.
Blood normal be-
fore 10 grs. qui-
nine given, but
slight hæmolysis
5 hours after. No
hæmolysis 3 days
afterwards. Se-
vere sloughing at
seat of injection.
4. Control
1,880
Ditto
. 25th August 12
12
Difficulty in breath-
ing after 40 minutes.
This difficulty in-
creased until death.
I
Died after 4
hours.
P. M. immediately
after death. No
clots in heart or
large vessels.
Blood apparently
normal, clotted
quickly and serum
slightly tinged red.
Slight hæmolysis
on centrifuging a
specimen in 1½
per cent. citrate of
soda in normal
saline solution.
The experiments in this table furnish no evidence of any tolerance having been established.
E 2
26
CHAPTER IV.
Remarks preliminary to a Detailed Examination of the Experiments
recorded in the next chapter.
Before dealing with the experiments in which tetanus spores and quinine were
used, it may perhaps be well to recapitulate a few of the leading points already
mentioned.
When tetanus spores are carefully prepared and freed from any traces of toxine
or contaminations of any kind, they may be injected into susceptible animals with-
out producing tetanus. This is an old and well known experiment, and never fails
when properly carried out. Its success depends on the fact that the phagocytes
can pick up and digest tetanus spores in the absence of any irritant or other material
likely to distract them ; but when virulent spores mixed with toxine, other bacteria,
or other spores, sterile powdered charcoal, sterile sand, quinine, lactic acid, or
anything which keeps away phagocytes, or occupies their attention, are injected
hypodermically into susceptible animals such as guinea pigs, or monkeys, tetanus
is the result.
These are facts which justify the statement that tetanus spores alone do not
produce tetanus. Before spores can give rise to tetanus they must germinate and
grow into bacilli, and these bacilli must elaborate an extra-cellular toxine which is
responsible for the disease and all its symptoms.
Now the question arises, when tetanus spores are injected hypodermically, are
they in all cases picked up and destroyed by the phagocytes ? or are some of them
stowed away locally, to remain dormant until some irritant or some other depressing
influence produces favourable conditions for their liberation and growth into toxine
producing bacilli ? Would a similar locking-up of tetanus spores take place when
wounds or abrasions are infected with spore containing material ?
The experiments recorded in this paper in addition to proving the influence of
quinine in favouring tetanus infections, will also throw some light on these obscure
points.
In some of these experiments tetanus cultures were used, but in most of them
washed spores, with and without quinine were used, the object being to prove
whether quinine helped in any way in the production of tetanus, and if so, what
was the nature of the assistance, and how it was brought about.
To save unnecessary repetition and at the same time to explain what actually
takes place when quinine and tetanus spores are injected into different parts of the
body of an animal, it may perhaps be well briefly to follow up each injection
separately.