THIOSINAMINE : 
A TREATMENT FOR “INOPERABLE” 
TUMORS AND CICATRICIAL 
CONTRACTURES. 
BY 
SINCLAIR TOUSEY, A.M., M.D., 
Assistant Surgeon, Roosevelt Hospital, Out-Patient Depart- 
ment; Instructor in Clinical Surgery, New York Post- 
Graduate Medical School and Hospital; Surgeon in Chief, 
St. Bartholomew’s Clinic. 
REPRINTED FROM THE 
Neto 3Todt if&cUtcal Journal 
for May 2, 1896. Reprinted from the New YorTc Medical Journal 
for May 2, 1896. 
THIOSINAMIJNE: 
A TREATMENT FOR “INOPERABLE” TUMORS AND 
CICATRICIAL CONTRACTURES. 
By SINCLAIR TOUSEY, A. M., M. D., 
ASSISTANT SURGEON, ROOSEVELT HOSPITAL, OUT-PATIENT DEPARTMENT ; 
INSTRUCTOR IN CLINICAL SURGERY, 
NEW YORK POST-GRADUATE MEDICAL SCHOOL AND HOSPITAL ; 
SURGEON IN CHIEF, ST. BARTHOLOMEW’S CLINIC. 
I have been experimenting with thiosinamine and 
studying the literature in regard to it for over a year and 
a half, and I think I have proved that it possesses positive 
curative properties in causing the resolution of benign and 
malignant tumors and the absorption of cicatricial tissue. 
So far as reported cases go, mine are the first in which 
it has been employed in the treatment of keloid and other 
neoplasms ; and, though the number of my cases has been 
small, the results have been positive. I believe that with 
increasing opportunity even greater action will be demon- 
strated than is now apparent. 
In addition to a number in which only one or two in- 
jections were made, my own cases were three of keloid, 
two of recurrent and “ inoperable ” carcinoma, and two of 
lupus. 
It will be fairer to earlier investigators, almost exclu- 
Copyright, 1896. by D. Appleton and Company 2 
THIOSINAMINE. 
sively as to its effect on lupus, to give the results of their 
observations, with corroborative or other statements of my 
own. Then I shall call attention to the lessons to be learned 
from my own cases. 
The substance itself is not at all a new one to chemists. 
It is amply described in the edition of Fownes's Chemistry 
which I studied ten years ago. Its first use in medicine 
was reported by von Ilebra before the Second Interna- 
tional Congress of Dermatologists, Vienna, 1892. He had 
experimented with it in the hope of finding in it a cure for 
lupus. A number of his cases were treated in a sanitarium, 
where they were constantly under observation, so that his 
description of its physiological effects is more complete 
than those of Van Hoorn, Keitel, Richter, Sedziak, and 
myself. If I fail to confirm some of his observations it 
may be because my opportunities for study have been 
more limited. 
llebra’s description of the drug is excellent: 
It is allvlsulphocarbamide, and is made by mixing two 
parts of oil of (black) mustard seed, one part of absolute 
alcohol, and seven parts of aqua ammoniae of the specific 
gravity of 0 960, warming to 104° F., and after a few hours 
evaporating over a water bath. The odors of mustard and 
ammonia disappear, and on cooling there are deposited 
crystals of allylsulphocarbamide, or thiosinamine The 
chemical class to which this belongs is shown as follows : 
NIL, NIIC3II5 
Urea is CO< Thiosinamine is CS< 
NII2 NHg 
Thus the oxygen has been replaced by sulphur in the car- 
boxyl, and one atom of hydrogen by the ally 1 radicle in the 
amine group. 
It is soluble in water, alcohol, and ether, but, like other 
mustard derivatives, decomposes in aqueous solution. It THIOSINAMINE. 
3 
occurs in small acicular crystals and has a bitter taste and a 
garlicky odor. 
The method in which thiosinamine was used by Hebra' 
was the hypodermic injection of a fifteen-per-cent, alcoholic 
solution into the muscular tissue between the shoulder 
blades. A fine needle was used, and the injection was made 
slowly and deeply. The beginning dose was from half to 
three quarters of a grain, and this was injected twice a 
week. In lupus cases the dose was increased in the third 
or fourth week to half or the whole of a hypodermic 
syringeful of a fifteen per cent, solution, equivalent to from 
a grain and a half to three grains of thiosinamine twice a 
week. These doses were as well borne as so much distilled 
water, but he says they always produced a visible curative 
effect. In a few cases he went as high as one and a half 
or two syringefuls with no bad effect. Keitel and Richter 
used a fifteen-per cent. alcoholic solution. I have used a 
ten per-cent, alcoholic solution, and Van Hoorn, on the 
recommendation of Professor Duclaux, of Paris, has used a 
ten-per-cent, solution in equal parts of water and glycerin. 
This he found just as active and not nearly so painful as 
the alcoholic solution. I shall try this in future cases. 
This solution has the further advantage of being available 
for use in agar agar cultures and the like, where the pres- 
ence of alcohol would interfere. 
Hebra, as has been said, rarely reached three grains; I 
myself have never exceeded a grain and a half ; but the other 
observers quoted used four grains and a half as a regular full 
dose, beginning, of course, with smaller ones. It appears 
to me that we should not try to give the largest doses that 
will be tolerated, but rather the smallest that will produce 
the therapeutic effect. 
In Keitel’s case and in my own cases the injections 
were into the muscles of the arm and forearm. In his 4 
THIOSINAMINE. 
case there was an effect which will be described; in mine 
there were no ill effects. The others all made the injec- 
tions into the muscles of the back. 
If an alcoholic solution is used there is sharp pain 
lasting for less than a minute. This may be somewhat 
diminished by pressure to diffuse the solution through the 
tissues. 
One very soon discovers that the syringe has to be 
washed out with water after the use of an alcoholic solu- 
tion, otherwise the leather washers on the piston become 
dried and loose. Hebra mentions a syringe made by 
Gutentag, of Paris, with a rubbePpiston which can be com- 
pressed and tightened by a screw. It would be ideal for 
this purpose. 
I found, as Hebra did, that it 5vas desirable to discon- 
tinue treatment for ten days every six weeks or two months. 
The others do not seem to have done so. 
Bacteriological studies of thiosinamine have been re- 
ported only by Hebra and Van Hoorn. Hebra at first 
found that rabbits were apparently made proof against 
anthrax, but in a second series of -experiments all the rab- 
bits died. Van Hoorn experimented in the Hygienic In- 
stitute in Amsterdam, with the assistance of Professor 
Forster. He found that the presence of a small percentage 
of thiosinamine in a culture medium rendered ineffectual an 
inoculation with certain bacteria. The addition of a few 
drops of a ten-per-cent, solution retarded or rendered im- 
possible the further growth of a culture ; but even flooding 
it with thiosinamine for twenty-four hours did not kill any 
bacteria. I have made no personal observations upon this 
subject. 
The physiological effects upon animals have been 
studied by Hebra alone, lie injected three grains daily 
for a month into a dog weighing twenty-two pounds. TIIIOSIN AMINE. 
5 
Three grains, it will be remembered, is the largest dose he 
ever used for a grown man. The dog remained perfectly 
normal, but became ravenous, and gained nine pounds in 
weight. lie further injected into curarized animals in the 
laboratory of Professor von Basch doses ten or twenty 
times greater in proportion to weight than in man. The 
only effect was a slight lowering of the pulse curve, and 
this was evidently due to the alcohol in which the drug 
was dissolved. 
Its physiological effect in man is in a general way that 
of a very mild tonic. If the subject is perfectly sound, 
there are no symptoms at all produced by the injections, 
and if there is a lesion present the reaction which may oc- 
cur is local, and is not accompanied by any general symp- 
toms. Especially, there is never any febrile movement. 
There is in all cases a tonic effect with an increase in 
weight. Thus far my own observations and those of all the 
others are in accord. Ilebra states that absorption is very 
rapid, since his patients noticed a garlicky taste in the 
mouth within a few minutes. The same author has noted 
an extraordinary diuresis, the increase in the daily amount 
of urine being two hundred or five hundred cubic centi- 
metres. In no case were there renal symptoms, or the 
presence of albumin or other pathological product in the 
urine. This diuresis ceases after a number of injections, 
lie thinks it is a therapeutic action and ceases after the 
abnormal fluids have been eliminated. Van Hoorn and 
Keitel, who both used large doses, noted after several 
weeks’ treatment the onset of nausea, headache, and lassi- 
tude. Hebra used smaller doses and I still smaller ones, 
and we have not had such an experience. 
Richter has studied its effect on the blood in a number 
of cases of lupus vulgaris, lupus erythematosus, ulcer of 
the leg, and cicatricial stricture of the urethra. He noted 6 
THIOSINAMINE. 
the number of white and red blood-cells, the amount of 
haemoglobin, and the changes in the morphology of the 
histological elements of the blood. Blood examinations 
were made just before the injection, four hours later, and 
again twenty-four hours afterward. In some cases exam- 
inations were made half an hour afterward, and in eight of 
these cases a change in the number of leucocytes had al- 
ready taken place. The blood was always obtained by 
pricking the finger tip and without pressure, and always at 
the same hour of the day. There was uniformly an imme- 
diate decrease in the number of leucocytes to one third of 
the normal number—viz., from about fourteen thousand 
down to four thousand to the cubic millimetre. But at the 
end of four hours the number of leucocytes had increased 
to normal or beyond, and in some cases there was well- 
marked leucocytosis which persisted for forty eight hours. 
There were no uniform changes in the number of red cells. 
The amount of haemoglobin was regularly increased. There 
was no special effect upon the number of eosinophile cells, 
but there was a uniform increase in the number of multinu- 
clear leucocytes or leucocytes with polymorphous nuclei. 
Richter states that in its action on the blood thiosina- 
mine belongs to the same class of substances as hemialbu- 
mose, peptone, pepsin, nuclein, pyocyanin, tuberculin, 
curare, urea, uric acid, and sodium urate. Lowit has 
shown that the intravenous injection of these substances 
causes an immediate leucocytolysis followed by leucocytosis. 
He thinks that the first effect is the cause of the second. 
Since it calls into the circulation new blood elements from 
the blood-preparing organs, it must necessarily stimulate the 
activity of those organs. Of course, the real cause of this 
leucocytolysis is still unexplained. 
There has been only one accident reported from the 
subcutaneous use of thiosinamine. It consisted in the pro- THIOSINAMINE. 
7 
duction of temporary cutaneous anteslliesia, and was ob- 
served by Keitel. The patient was a robust youth with 
recurrent psoriasis of a papular type, and thiosinamine was 
used with a view to causing absorption. The injections 
were made at various points, and the last one into the 
muscles of the extensor aspect of the forearm. This 
was followed very shortly by complete anaesthesia of the 
skin supplied by the cutaneous branch of the musculo- 
spiral nerve. It could not be stated positively that the 
nerve had been wounded by the needle, which I think 
probable, and Keitel thinks the effect due to the action of 
the drug itself upon the nerve. Temporary motor or sen- 
sory paralysis is not altogether unknown as an effect of 
the hypodermic method of medication. Thus, paralysis 
of entire groups of muscles after hypodermics of ether 
have been reported by Remak, Mendel, and Brieger. 
Purely cutaneous anaesthesia is not nearly so common, but 
two cases have been reported by Falkenheimer and Mobius. 
The former’s was the result of a hypodermic of ether and 
the latter’s of one of a solution of antipyrine. 
In all these cases the disturbance of function was only 
temporary. This would seem to be a slight objection to 
any hypodermic medication, and not particularly to the 
use of thiosinamine. In one of my own cases twenty-seven 
hypodermics of thiosinamine were administered in the left 
biceps at approximately the same spot without any unfavor- 
able effect. 
Its effect upon pathological conditions is that of a pow- 
erful absorptive, acting probably by increasing the activity 
of the lymphatic system. This effect is seen in the ab- 
sorption of serous exudations, accompanied, as before 
stated, by marked diuresis. It is also visible in its effect 
upon lupus, corneal opacities, cicatrices, glandular swell- 
ings, and neoplasms. Hebra used it in a number of tu- 8 
THIOSINAMINE. 
berculous patients who had had no recent pulmonary 
symptoms, and observed a return of fever after the injec- 
tions. In such cases the fever is perhaps due to the absorp- 
tion of encapsulated pus. In one case of his with very 
severe night sweats there was repeatedly a marked ameliora- 
tion following the injections. This was verified by control 
experiments. This same absorptive effect is so active 
locally that in some classes of cases a latent process may 
be fanned into an active one. This is especially the case 
in its use for clearing up opacities of the cornea; if there is 
the slightest inflammatory condition present this will be 
very much aggravated, and treatment will have to be sus- 
pended. In some cases this local inflammatory reaction is 
of benefit. Cases have been reported in which an appar- 
ently cured osteomyelitis has started up again after the 
injections—a new abscess has formed, a sinus has opened, 
and an old sequestrum has been extruded. This has been 
followed by definitive healing, and the entire process could 
only be regarded as having been a beneficent one. 
Its use in the treatment of lupus is of historical inter- 
est, since that was its first therapeutic application. The 
results obtained by Ilebra, Fiichter, Van Hoorn, and my- 
self are somewhat at variance. Ilebra and Van Hoorn ob- 
served in practically every case a local reaction which they 
describe as beginning two or three hours after the injec- 
tion. The diseased part becomes red and swollen, some- 
times so much so as to cause fissures in the surface. There 
is no vesication and there is little if any serous exudation. 
This reaction remains undiminished for five or six hours, 
but at the end of twenty-four hours has entirely disappeared. 
Marked desquamation sometimes follows. There is never 
a general reaction, and especially there is no fever. There 
is a sensation of heat and tension in the affected part. These 
two authors report this reaction to have occurred in practi- THIOSINAMINE. 
9 
cally every lupus case, and to have been repeated without 
material increase of the dose after each injection. My own 
lupus cases have been in dispensary practice, and the pa- 
tients have not been seen until forty-eight hours after the 
injection. So far as the patients’ statements can be counted, 
my cases have not shown a local reaction. Richter had a 
comparatively large number of cases of lupus (eleven), and in 
only two was there any reaction, and then only with the first 
two or three injections. His cases, as we have seen, were 
under constant observation, and the doses used were large. 
As to the curative action upon lupus, Van Hoorn and 
Ilebra observed a very great effect indeed wherever the 
superficial area of disease was great. Ulcerations healed, 
and the thickened and nodular edges flattened out. No 
case of complete cure is reported, and where the area in- 
volved was quite small—lupus of the cheek of the size of a 
dime—it was hardly influenced at all. Richter has seldom 
seen any effect at all upon lupus. In my own cases no 
“ reaction ” has been noted, but I have uniformly seen a 
diminished vascularity and a softening of the edges with 
healing of the ulcer. I agree with the other authors quoted 
that local treatment is a better means of handling lupus 
than the use of thiosinamine. 
Its therapeutic application in clearing up corneal opaci- 
ties has been attended with almost perfect success in the 
hands of all the investigators. Hebra had a patient who, 
before the injections, could hardly avoid collisions with 
people on the street, and afterward the acuteness of vision 
had so increased as to enable him to tell the direction of 
the wind by the weather vane on the high Rathhausthurm 
(city hall tower) in Vienna. He and Richter report a num- 
ber of such cases, and give the formulae for vision before 
and after treatment, demonstrating a remarkable increase. 
This is to my mind of the greatest possible importance, 10 
THIOSINAMINE. 
for we can promise almost all these patients an astonishing 
improvement in vision. The cases for which it is unsuit- 
able are those in which a vestige of inflammation is still 
present and might be started up into fresh phlyctenulae. 
In the treatment of cicatricial contractures thiosinamine 
acts by causing absorption of the fibrous tissue, whether 
located in the skin or in deeper parts—such as tendons and 
ligaments ; and all the authors cited report complete cures 
of such cases. AmoDg these are ectropion following lupus 
of the cheek, partial ankylosis of the knee from lupus, and 
talipes equinus following an injury (burn) of the leg. One 
case of ectropion was so marked that the eye could not 
possibly be closed, the tarsal cartilage was so rarefied by 
pressure and traction as to be scarcely perceptible, and even 
the corner of the mouth was drawn up toward the eyelid. 
This patient was restored to a normal condition, and the 
skin of the cheek became soft and freely movable on the 
subjacent tissues. In another case of Ilebra’s there was 
such contracture following lupus of the palm that the finger 
nails grew into the flesh. Complete extension was possible 
after about twenty-five injections, no other treatment hav- 
ing been employed. It was this wonderful absorptive power 
over cicatricial tissue which suggested to my mind its use 
in keloid and malignant neoplasms, in which I believe I am 
the first investigator. 
In the treatment of simple ulcers and of stricture of the 
urethra, Richter’s half-dozen cases, with an average of eight 
injections, gave negative results; but I should not regard 
this as final. In the case of stricture of the urethra or rec- 
tum,! believe this might be a very valuable adjunct to local 
treatment. 
Its action upon chronically enlarged glands has been 
observed by Hebra, and it is to cause a very rapid absorp- 
tion. In syphilitic cases, on the other hand, absorption was TIIIOSINAMINE. 
11 
not effected; and he believes that this may in some cases 
be of diagnostic value. He and the other authors cited have 
not used it in the treatment of glandular swellings secondary' 
to epithelioma or carcinoma, some of which are described 
below from my own experience. It has been used with 
success for uterine myomata. 
It has been used with negative results in eczema, psoria- 
sis, and lupus erythematosus. 
A case of mine, which I wish to describe in detail, was 
one of keloid. A study of the action of the drug as de- 
tailed above led me to believe it the ideal non-operative 
treatment for these neoplasms. 
The patient, Patrick M., was a mechanic, thirty-two years 
old. In September, 1893, his left arm was burned from 
shoulder to fingers. An area about four inches and a half in 
diameter immediately above the elbow healed by granula- 
tion, the rest being more superficial. About four months 
after the accident the cicatrix began to itch and burn, and 
very soon a hard, prominent mass had formed in the scar. 
When he was admitted to St. Bartholmew’s Clinic, July 7, 
1894, he presented a typical keloid, consisting of two areas, 
each of the size of a silver dollar and projecting three quarters 
of an inch above the surface. These were on the flexor as- 
pect of the arm just above the bend of the elbow. The treat- 
ment consisted in hypodermic injections into the left biceps 
twice a week. It should be mentioned that he applied for 
treatment because of impaired motion at the elbow. Tbe be- 
ginning dose was two thirds of a grain of thiosinamine, in ten- 
per-cent. solution in absolute alcohol, and the highest dose 
used was a grain and a half. These injections produced no 
special effect except on the neoplasm. After one or two treat- 
ments this became very much paler, and after twelve injec- 
tions one portion had lost its thickening and induration. 
This part was then visible as apparently normal skin, but a 
little paler than the rest. The other area gradually changed 
to the appearance of normal skin. The cure was complete 12 
TIIIOSINAMIXE 
after twenty-seven injections bad been made. Complete use 
of the arm was restored, and there was no thickening or ad- 
hesion of the skin, though the cicatrices were, of course, still 
recognizable. 
Another patient, J. E., was referred to me by Dr. Frank 
Hartley for treatment by this method. He had been operated 
upon by another surgeon for carcinoma of the inferior maxilla, 
and there was an “ inoperable ” recurrence involving the lar- 
ynx, the pharynx, and the glands of the neck. Ulceration had 
taken place. The effect of a few injections was very apparent 
indeed. The induration became somewhat less, and the foul 
sloughing surface became cleaner. Unfortunately, he learned 
at this time of the existence of a faith curer and abandoned 
treatment. He died some three months later. 
There are reserved for another paper the description of 
additional cases and the consideration of the selection of 
cases for this treatment in preference to local means. 
To recapitulate: We have in thiosinamine a drug pro- 
ducing, when given hypodermically, no general symptoms, 
and even when long continued no harmful effects. It acts 
specifically upon certain abnormal tissues to cause their 
absorption or conversion into normal tissues. It is of 
doubtful efficacy in lupus and a variety of skin diseases. 
But it is of the greatest possible value in the removal of 
cicatricial contractures following lupus or any other cause 
of loss of substance. The frightful contractures from 
burns of the neck would yield to its action, as cases of ec- 
tropion and corneal opacity do. My own cases have shown 
its curative effect upon keloid, and its palliative and prob- 
ably curative effect on malignant tumors. 
A. On Thiosinamine. 
Bibliography. 
von Hebra, H. H. Internat. Min. Rundschau, 1892, vi, 1497 
and 1583. 
von Hebra. Wien. med. Bl., 1892, xv, 605. TIIIOSINAMINE. 
13 
von Hebra. Monatshefte f prakt. Dermatol., 1892, xv, 337 
and 432. 
Richter. Wien. med. Woch., 1893, xviii, 1212 and 1257. ' 
Van Hoorn. Monatsh. f. prakt. Dermat., 1894, xviii, 605. 
Sedziak. Pam. Towarz. Lek. Warsaw, 1893, lxxxiv, 785. 
Keitel. Charite Annalen, Berlin, 1891 and 1892, xviii, 
639. 
B. On Collateral Topics. 
Lowit. Physiol, des Blutes und der Lymph, Jena, 1892, 
p. 24. 
Remak. Berl. klin. Woch., 1885, Ko. 5. 
Falkenheimer. Mittheilungen aus der med. Klinik zu 
Konigsberg, 1888. 
Mobius. Schmidt’s Jahrbucher, 1889. 
29 West Thirty-eighth Street.