NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
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this time varies with the temperature, as uniform a temperature as possible is
advisable. " Half blood temperature," 18.5°C (65.°F) is recommended by Dr.
Wright, is obtained by placing the tubes in small pockets of a bandage fitted
around a metal vessel which can be filled with water of the desired temperature.
One other fallacy has to be eliminated, namely, the effect of a full meal in
slightly accelerating, and of a prolonged fast in retarding the coagulability of the
blood. I made some preliminary observations to determine the extent of this
influence. Thus one day I had tea and toast at 7 A.M., breakfast at 9-30,
and then fasted until 8 P. M., taking two-hourly observations which resulted
as follows : At 9 A.M. my coagulation time was 4 min. 15 sec., at 11-30 A.M
.=4 min., at 1-30 P.M.=4 min., at 3-30 P.m.=4 min., at 5-30 P.M.=from 4
min. 15 sec. to 4 min. 30 sec., at 7-30 P.M.=4 min. 15 sec., and at 10 P.M.
=4 min. Thus the greatest variation was less than half a minute, and by taking
a light lunch at 2 P.M. even this difference may be lessened.
Again, exercise might possibly influence the coagulation-time, but the
following observation seems to show that it exerts no material effect on it.
Thus a 14 mile march followed by being out shooting from 11-30 A.M. to 5-30
P.M. one day, and a 13½ mile march the next morning produced no alteration
of my coagulation-time. Alcohol has been shown by Dr. Wright to retard
coagulation, so throughout the 7 months over which my experiments have
extended I have taken no alcoholic drinks. In fact from nearly 150 observations
I have come to the conclusion that at a given temperature my coagulation-time
is remarkably constant, and as no conclusions have been drawn from less than
three experiments with the same drug, and from an acceleration of less than
from a half to one minute, all known sources of fallacy may be fairly claimed
to have been excluded.
I now pass on to the consideration in detail of the results obtained, begin-
ning with the class of so-called hæmostatics, as the main object of this investi-
gation was to determine in what degree, if any, the power of these drugs in
checking internal hæmorrhage depends on their effect in accelerating the clotting
power of the blood, the rapidity of this action, and how long it continues. As
yet I have only determined this for single doses.
Calcium Chloride.
This salt is the most powerful coagulation accelerator known, as has been
fully shown by Dr. Wright,* with the exception perhaps of the inhalation of
carbonic acid gas.† I will give one typical experiment here which I did at
Netley in 1893 to illustrate its range of action.
Experiment. —My coagulation-time having been found to be 5¼ minutes both
in the morning and afternoon, I took 1 gramme (15 grains) of calcium chloride
at 7 P.M. and the same dose again at 7 A.M. the next day. At 3 P.M. my
* British Medical Journal, 1893, Vol. II, page 223.
† B r i t i s h M e d i c a l J o u r n a l , 1 8 9 4 , V o l . I I , p a g e 5 7 .
ti
Medical Officers of the Army of India. 61
time was 1¾ minutes, a day later it was 3½ minutes, and on the 4th day it had
regained its former time of 5½ minutes. I may just mention here that on three
occasions I have seen severe hæmoptysis cease in from 10 to 20 minutes after a
single gramme dose of calcium chloride, in two of which other drugs had
previously failed to control it. That this very rapid effect was really due to the
action of the drug and not to a series of extraordinary coincidences is borne out
by the following observation. My coagulability-time being 3 minutes at 11-45
A.M. I took 1 gramme (15 grains) of calcium chloride at 12 noon. At 12-30
my t i me wa s 1 mi n. 30 s e c . Thus i n ha l f a n hour my c oa gul a t i on- t i me wa s
a c c e l e r a t e d by 1 mi n. 30 s e c . , or by one - ha l f . Ca l c i um c hl or i de ha s , howe ve r ,
one great disadvantage, namely, that if the dose be increased or frequently
repeated, not only does its effect not increase proportionately, but is actually
decreased until it has an opposite effect. It cannot then be used to keep up
a definite increase of coagulability over a long period of time, as, for instance,
in the treatment of aneurism.
Turpentine.
Experiment at 10-30 A.M. Coagulation-time, 4 min. 30 sec. Oil of turpentine 3ss
at 10 - 4 0 A . M .
„ 12-40 ,, ,, ,,
3 „ 15 „ or an acceleration of 1
min. 15 sec. after 2 hrs.
„ 2-40 P.M.
,, ,,
3
,, ,, ,, ,,
min. 30 sec. after 4 hrs.
,,
4-30
,, ,, ,,
4
,,
„
,, ,,
min. 30 sec. after 6 hrs.
The effect was therefore passing off in 6 hours.
On other occasions the effect was not quite so marked as in the above
experiment, but the acceleration was never less than half a minute ; it had nearly
passed off after 12 hours, completely in 24 hours.
The good effect of turpentine in controlling internal hæmorrhages is thus
in part at least due to its power of increasing the coagulating power of the blood.
Its action is rapid, but also passes off quickly. As its effect is a general one on
the blood, it may be used with advantage in hæmorrhages other than those
from the alimentary canal as I have had occasion to verify clinically. In fact
I look on it as one of our most useful hæmostatics.
Gallic and Tannic Acids.
These may be considered together, as tannic acid is said to be absorbed in
the form of gallic acid.
Experiment at 11-45 A.M. Coagulation-time being 3 min. Gallic acid gr. 40 was
taken at 11-50 A.M.
„ 3-50P. M.
,, ,,
was 2 „ 30 sec., an acceleration
of 30 sec. after 4 hours.
,,
7-50
,, ,, ,, ,,
3 „ the effect having passed
off.
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On another occasion an acceleration of 55 sec. followed 4¼ hours after
taking 30 grains of gallic acid.
Experiment at 10-30 A.M. Coagulation-time being 4 min. Tannic acid gr. 20 was taken
at to-35 A.M.
„
1-30 P.M.
„ „
was 3 „ 35 sec., an acceleration of 25
sec. after 3 hours.
„
4-30 ,,
„ „
„ 3 min., an acceleration of 1 min.
after 6 hours.
This effect had quite passed off by noon the next day.
Thus these drugs appear to have a distinct effect in accelerating coagula-
tion, which takes some hours to develope and passes off fairly quickly, They
are not so powerful as some of the other drugs tried. As was to be expected,
tannic acid acts somewhat more slowly than gallic acid.
Persalts of Iron.
Although I cannot find any reference to the use of iron internally as a
hæmostatic except in cases of hæmatemesis, etc., where its action is a local one,
I was led to investigate its effect on intravascular coagulation by thinking of its
powerful local action in causing blood to clot, and obtained the following inter-
esting results :—
Experiment at 10-30 A.M. My coagulation-time being 4 min. I took liquor ferri per-
chloridi 3ss. at 10-35
A.M.
„
1-30 P.M.
„
„ was 4 „ 45 sec., a retardation of
45 sec. after 3 hours.
,, 3-35 ,,
„ „ „
2 „ 15 sec., an acceleration
of 1 min. 45 sec. after 5
hrs.
„
7-40
„ „ „
„ 2 „ 45 sec., an acceleration
of 1 min. 15 sec. after 9
hrs.
The next day „ 10-30 A.M.
„ „ „
2 „ 15 sec., an acceleration
of 1 min. 45 sec., after
24 hrs.
Again
„ 10-30 „
„
„ being 3 „ I took liquor ferri per-
chloridi 3i at 10-45 A.M.
,, 12-45 P.M.
„ „
„ 2 „ 15 sec., an acceleration
of 45 sec. after 2 hours.
„
4-45 ,,
„ „
,, 2
„
an acceleration of 1
min. after 6 hours.
„
7-45 ,,
„
,,
„
1 „ 45 sec., an acceleration
of 1 min. 15 sec. after
9 hrs.
Medical Officers of the Army of India.
63
Next day at 10-50 A.M. My coagulation-time being I min. 30 sec., an acceleration
of 1 min. 30 sec. after
24 hrs.
Again
„ 10-30
„
,,
„
being 3 „ I took liquor ferri per-
nitratis min. 40 at 10-45
A.M.
„ 1-0 P. M.
„
„ was 4 min., a retardation of 1 min.
after 2¼ hours.
At 3-45 P.M., my coagulation-time was 2 min. 30 sec., an acceleration of 30 sec.
after 5 hours.
Next day at 10-30 A.M.
„ „ „
3 ,, the effect having
passed off in 24 hours.
Thus the minimum pharmacopœal doses of both salts were followed by a
primary retardation of the coagulation-time, and this was quickly superseded
by an accelerating effect more marked and more persistent in the case of the
chloride, whilst after a one drachm dose of the perchloride an immediate
gradually increasing and persistent acceleration occurred. The perchloride of
iron has then a marked accelerating effect which is more lasting than any other
drug I have yet tried, with the exception of calcium chloride. I have hopes
that it will prove even more reliable than that salt in cases where it is wished to
keep up an increase of the coagulation-power of the blood over some days as
in the treatment of aneurisms, scurvy, hæmophilia, etc.
Ergotin.
Ergotin was taken in the full pharmacopœal dose of 5 grains, on three
separate occasions, and observations made from two to four and a half hours
afterwards. In no case was any alteration of the coagulation-time produced.
Ergotin, therefore, does not act by increasing the clotting power of the blood, and
as its effect in increasing arterial tension at least partly neutralises its power in con-
tracting the arterioles, its value as a haemostatic in hæmorrhages other than those
from the uterus is, I believe, little or none.
Haniamelis.
In four experiments with the liquid extract of this drug, in doses of from
fifteen (15) minims to two drachms, on only one occasion was any acceleration
produced, and then of less than half a minute, The efficiency of this drug,
more especially in oozing hæmorrhages, does not appear to be dependant on
any effect on coagulability. According to Wood and Marshall it has absolutely
no physiological action.
Dilute Sulphuric Acid.
This acid in half drachm doses produced no effect on the coagulation-
time, but one drachm was followed by a slight acceleration. Thus my coagula.
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Scientific Memoirs by
tion-time being 3 min. at to-35 A.M., I took of acid sulph, dil. 3i at 11 A.M. At
1-30 P.M. and again at 4 P.M. my coagulation-time was 2 min. 30 sec., or a
quickening of 3o sec. at both 2½ and 5 hours, respectively, after this dose. Sul-
phuric acid has then only a slight accelerating influence when given in a full dose.
Lead Acetate.
Experiment at 10-30 A.M. My coagulation-time being 3 min. 30 sec., lead acetate gr.
5 was taken at 10-50 A.M.
at 12-50 P.M.
„ „
was
2 min. 40 sec., an acceleration
of 50 sec. after 2 hours.
at 3-50 P.M.
„ „
was 3 min.
and at 4-45 P.M. the next day it was 2 min. 15 sec., an acceleration of 1 min- 15
sec. persisting 30 hours after taking the drug. On other occasions an accelera-
tion of from 25 sec. to 1 min. has been observed, but the effect has in some in-
stances passed off in 24 hours.
Thus lead acetate has a distinct and fairly persistent accelerating effect on
coagulation, sufficient to account for its known value as a hæmostatic, especially
in combination with other drugs.
Potassium Iodide.
This salt is not used as a hæmostatic, but as it is very frequently given
for long periods in cases of aneurism, even when there is no suspicion of syphilis,
I thought it would be of interest to determine if it had any effect on the coagu-
lation of the blood. In my first experiments with this drug I obtained negative
results three and four hours, respectively, after single 20-grain doses. However,
on repeating the experiment, and making observations at longer intervals, I
obtained the following interesting effect :—
Experiments at 10-45 P.M. My coagulation-time being 3 min., I took potassium
iodide, gr. 20, at 10-50 A.M.
at 1-45 P.M. ,, ,, ,,
was 3 min. 45 sec., a retardation
of 45 sec. after 3 hours.
at 3-50 P.M. „
,, ,,
,, 1 min. 45 sec., an acceleration
of 1 min. 15 sec. after 5 hours.
at 7-20 P.M. „
,, ,,
was 2 min., an acceleration of
1 min. after 8½ hours.
but the next day at 10-15 A.M.
,, ,,
„ 3 min. 20 sec., the effect
having quite passed off in 24 hours.
Again
at 10-15 „
,, ,,
being 3 min. 20 sec., I took pot-
assium iodide, gr. 20 at 10-30 A.M.
at 1
P.M.
,, ,,
was 2 min. 30 sec., an acceleration
of 50 sec. after 2½ hours.
at 4-30 P. M.
”
,, ,,
2 min. 15 sec., an acceleration
of 1 min. 5 sec. after 6 hours.
Medical Officers of the Army of India. 65
Thus single 20-grain doses of potassium iodide caused a marked accelera-
tion of coagulation in from five to eight hours (in one instance preceded by a
primary retardation) passing off in twenty-four hours. Its clinical use in cases of
aneurisms thus receives an additional physiological basis.
In addition to the above, I have also investigated the action of some of the
vegetable acids which Dr. Wright has found to diminish the coagulability of the
blood.* My results are, however, much more variable than his, as,will be seen
from the data given below :—
Citric Acid.
Experiments (1) at 10-25 A.M. My coagulation-time being 3 min., I took citric acid
3i, at 10-45 A.M.
at 12-45 P.M.
„ „ „
was 3 min., or no change after 2
hours.
at 2-40 P.M.
„ „ „ „
2 min or an acceleration
of I min. after 4 hours.
at 4-30 P.M
„ „ „ „
2 min. 30 sec., or an ac-
celeration of 30 sec. after 6 hours.
(2) at 10-25 A.M
„
„
„
being 2 min., I took citric acid 5
grammes (3iiss.) at 10-45 A. M.
at 12-40 P.M
„ „ „ was 2 min., or no change after 2
hours.
at 2-45 P.M.
„ „ „ „
2 min. 30 sec., or a re-
tardation of 30 sec. after 5 hours.
(3) at 10-20 A.M.
„
„ „
being 2 min. 45 sec., I took
citric acid 5 grammes at 10-55 A.M.
at 12-55 P.M.
„ „ „
was 3 min. 15 sec., a retardation
of 30 sec. after 2 hours.
at 3-35 P.M.
„ „ „ „
3 min. 30 sec., a retardation
of 45 sec. after 5 hours.
Thus in one case an actual acceleration was observed, and in the others the
retardation was much less marked than in the case of Dr. Wright's experi-
ments. Possibly my citric acid, which was, however, obtained from two different
sources, was not pure, but this I have no means of testing.
Tartaric Acid.
Again in the case of tartaric acid I twice observed a slight acceleration to
follow 3i and 5 gramme (3iiss.) doses, respectively, and on one occasion a
decrease of I min., 2½ and 5 hours after a 5 gramme dose, but in this case my
* British Medical Journal, 1894 Vol. II, page 57.
1
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coagulation-time had been previously accelerated to I min. 3o sec. by a dose of
a persalt of iron taken the day before, so the decrease may have been due to the
effect of the iron passing off. Here again my tartaric acid, which was obtained
from a Calcutta chemist, may possibly not have been pure.
Lime—Juice.
Lime-juice on the other hand, when taken in one ounce doses, has uniform-
ly been followed by a marked retardation of coagulation.
Experiment at 10-30 A.M.
My coagulation-time being 3 min, 3o sec., I took
lime-juice 3i. at 10-40 A.M.
at 12-4o P.M.
,,
„
was 5 min., or a retardation
of I min. 3o sec. after 2 hours.
at 3-30 P.M.
"
,,
„ was 4 min., a retardation of
30 sec. after 5 hours.
On other occasions a retardation of 1 min. 45 sec. and 1 m i n . , r e s p e c t i v e l y ,
was noted 2 hours after taking one ounce of lime-juice, but the effect had in one
instance passed off again in 4 hours.
As the Board of Trade standard lime-juice only contains 30 grains (or 2
grammes) of citric acid to the ounce, this vegetable acid seems to have a greater
power of diminishing coagulability when given in the form of lime-juice than as
the pharmacopceal drug, a point I am unable to account for unless it is due to the
alcohol which is added to some brands, as, for instance, that used in the navy.
This fact should be borne in mind in treating cases of scurvy with a marked
tendency to h ae morrhages, and same coagulative accelerator given before the
lime-juice, of which I would suggest the perchloride of iron as the most suitable,
or sodium citrate substituted for the lime-juice as first suggested by Dr.
Wright.*
This concludes the list of drugs I have up to the present time experimented
with. The clinical bearing of many of the observations will be at once obvious, but
these I fully entered into in my paper read before the Indian Medical Congress,
and this is not the place to dilate on them. I hope, however, to be able to give
the results of further experiments on the effects of repeated doses of single and
combined drugs on intravascular coagulability in a future paper.
* B r i t i s h M e d i c a l J o u r n a l , 1 8 9 4 , V o l . I I , p a g e 5 7 .
67
Is Mycetoma primarily owing to the action of the fungal elements
ordinarily associated with its products ?
BY
BRIGADE-SURGEON LIEUTENANT-COLONEL D. D. CUNNINGHAM,
C.I.E., F.R.S.
To most pathologists it will probably appear to be very heterodox to retain
any doubts in regard to the relation which the presence of the fungal elements
in the morbid products of the disease bear to Mycetoma. The long recognised
association of masses of large fungal elements with the black concretions of the
one form of the disease and Mr. Kanthack's recent demonstration of the pre-
-sence of actinomyces-like structures in the roe-like bodies of the other* will.
probably appear to most pathologists to be conclusive evidence that these consti--
tute the essential and primary contagium vivum on which the affection is
dependent. There appear, however, to be certain phenomena which still render
this doubtful, and it is to these that I propose to call attention in the following
pages. They are the following : 1st, that a certain number of cases occur in
which, whilst all the other essential symptoms of the disease are present, there
is an entire absence of any concretions of either the black or white variety and
of the fungal elements ordinarily associated with them ; 2nd, that the
fungal elements which ordinarily occur in connection with the two varieties of
the disease are of absolutely unlike character, those associated with the white
variety resembling those of actinomyces, and those of the black variety forming
sclerotia like those of the Sclerotiniæ and other allied ascomycetes ; 3rd, that
this very formation of sclerotioid bodies is a process which is normally indicative of
a cessation of vegetative growth dependent on exhaustion of nutritive supply, and
therefore one which could not occur were the normal tissues the proper site for the
development of the parasitic elements. Were the normal tissues the primary site
in which the latter establish themselves, there could be no reason for a cessation
of the indefinite extension of mycelium and for the formation of dense sclero--
tioid aggregates until they had been throughout affected and exhausted, where-
as, as a matter of fact, we find the sclerotia isolated and surrounded by masses
of tissue entirely devoid of fungal elements.
Taking these points in detail, we have first to consider the question of the
possible existence of the disease without the presence of any of the fungiferous
* Madura disease (mycetoma) and actinomycosis. A. A. Kanthack, Journal of Pathology and
Bacteriology, October 1892.
1 2
I2
70 Scientific Memoirs by
Now in regard to this, it must always be carefully kept in mind that Oospora
is not a term of truly generic value at all, but a mere provisional one applied
to a number of fungi which have not yet been definitely classified, because we
are as yet only very imperfectly acquainted with their true nature. In many
cases the mycelium alone has been as yet detected, and in those cases in
which any fructification is present, it invariably consists of conidia or pos-
sibly in some cases of chlamydospores, neither of which are of determinative
value in questions of classification. When, therefore, we describe any fungal
growth as an Oospora, we do not by any means imply that it necessarily has
any really close affinity to any of the other fungi included in the same group
with it, All that we mean is that it is a fungal organism whose precise nature
we are not at present in a position to determine. But, if this be so, we are
most assuredly not in a position to determine questions of the specific identity
of the different forms which, as a matter of convenience, are included within
the provisional genus. Even in those cases in which fructification is present,
this still holds good, for the forms of fructification which occur are not of
determinative value. This must at once be evident to every one when it is
taken into account that the conidial fructification, which used formerly to be
described as Botrytis cinerea is seemingly common to many distinct species
of Sclerotinia. But in the case of the fungal organisms associated with my-
cetoma we have no fructification of any kind to aid us, and hence any satis-
factory identification becomes even more impossible. No one would dream
of affirming that any two specimens of Zygomycete mycelium belonged to one
and the same species of fungus, however identical in character they might
be, in the absence of any fructification, and when we have not only no fructi-
fication as a guide, but there is in addition no resemblance, but very conspi-
cuous differences between two mycelia, as is the case with the two varieties of
mycetoma, in place of having any satisfactory ground for affirming that they
are specifically identical, we have very good ground for suspecting that they
are specifically distinct.
The mycelium discovered by Mr. Kanthack in the concretions of the
white variety of mycetoma is practically identical in characters with that oc-
curring in actinomycosis, but this most assuredly is not the case with re-
gard to that which is normally associated with the black variety. Mr. Kan-
thack apparently encountered a specimen in which the fungal elements, or some
of them at all events, did resemble those normal to the white variety, but
this must not be taken as indicating that as a rule they do so. On the con-
trary, all the specimens of the black variety which have been studied by other
observers from the days of Carter to those of Boyce and Surveyor are described
as containing a mycelium presenting no resemblance whatever to that charac-
teristic of actinomyces, which is characterised by the absence or extreme