NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
INVESTIGATIONS ON THE TOXICITY OF CRINUM
DEFIXUM KER-GAWL, I
BY
M. R. SUBRAMANIA SASTRY
C. K. VELAYUDHAN NAYAR
R. RAMASWAMY
AND
K. VENKATACHALAM
The Research Unit, Medical College, Madras
(Received for publication on 21 January 1942)
(With Plate VII)
O N a report that cases of poisoning by Crinum defixum Ker-Gawl (Family
Amaryllidaceae) had been occurring in cattle around Mettupalayam,
in Coimbatore district, Madras province, a toxicological investigation was
undertaken on this plant.
Crinum defixum is a native of the Concan, Coromandel, and of many parts
of Bengal. It is also said to be common on the banks of the Deccan rivers,
and grows well in muddy and swampy places. This species has no stem, but
possesses a spherical bulb and succulent leaves (Plate VII). An average-sized
bulb has a circumference of about 2 to 4 inches, and its roots penetrate into
the mud. This plant generally flowers at the end of the rainy season. The
flowers are large, sessile, white and fragrant during night. The bulbs are
extremely acrid [Watt, 1889].
Attempts were made to determine the degree of its toxicity, the mini-
mum lethal dose orally and the cumulative effect, if any.
A. The degree of toxicity
Feeding experiments, both with bulbs and leaves, were made on dogs of
different ages. They were dried, powdered and suspended in water. The
feeding was done with the aid of a stomach tube.
(1) Bulbs (Crude). Eight dogs both young and old were fed with
bulbs, powdered and suspended in water. Of these two died, but six re-
covered after showing severe toxic symptoms. An aqueous extract of the
bulbs was also given to six dogs, five of which recovered after exhibiting more
or less severe symptoms of poisoning, but the sixth one died. The residue
after the removal of the extract was also fed to two dogs ; both of them showed
similar toxic symptoms in a lesser degree and recovered. The results of these
experiments indicate that (1) the bulbs are definitely toxic and (2) the toxic
principle or principles found in these are only partially soluble in water, as is
evident from the fact that both the aqueous extracts and the residue have
produced toxic symptoms in different degrees. The details of the experiments
are given in table I.
(2) Leaves. Six young dogs were fed, two with the powdered leaves,
two with the aqueous extract of the leaves and two with the residue left
65
66
Toxicity of Crinum defixum Ker-Gawl, I
Table I
Preparation used
1
(a) Dried
and
powdered bulbs
(b) Aqueous extract
of the bulbs
(c) Residue left after
removal of
the
aqueous extract
No. of
dogs
fed
2
8
6
2
Dose
given per
kg. of
body
weight
(gm.)
3
3
3
3.5
3.5
3.5
3.5
3.5
3.7
2
3.5
3.5
3.5
3.5 3.5
3
3
Total
quantity
fed
(gm.)
4
22.8
14.7
28
27.3
29.4
29.4
25.5
25
7.3
28
29.4
27
21.5
30
26.1
15
Whether the
symptoms
shown were
severe or
moderate
5
Less severe .
Do.
Do.
Do.
Do.
Do.
Severe .
Do. .
Moderate
Do.
Do.
Do.
Do.
Acute .
Less severe .
Moderate .
Whether
died or
survived
6
Survived
Do. .
Do.
.
Do. .
Do. .
Do. .
Died .
Do.
.
Survived
Do. .
Do. .
Do. .
Do. .
Died .
Survived
Do. .
Observations
7
About 15 minutes after feeding there was frothing from the
mouth, salivation which gradually became profuse, severe
attempts at retching, bile tinged emesis, diarrhœa (the faeces
being bile tinged in some cases), rise of temperature, initial
excitement followed by depression of the heart reduced pulse
rate and respiration, congestion of visible M. M. in some cases,
distressed breathing followed by drowsiness and stupor in
cases which recovered. Those ended fatally showed extreme
restlessness, severe respiratory embarrassment with the head
protruded, prominent eyes, anxious expression, rubbing the
nose on the ground or with one or both the forepaws, unsteadi¬
ness in gait, whining, jumping about and falling down uttering
a pitiable cry. Post-mortem examination held on the cases
ending fatally, revealed lesions which were almost constant in
all the cases and they were :—
(1) Basal congestion of the lungs with few areas of atalectesis;
(2) Engorgement of the superficial blood vessels of the heart;
(3) Presence of clotted blood in both the chambers of the right
side of the heart while those of the left side remained
mostly empty.
(4) Petechial haemorrhages under the endocardium mostly of
the left ventricle and in some cases of the right ventricle ;
(5) Congestion of the blood vessels of the mesentery and
intestinal walls ;
(6) Congested and friable condition of the liver;
(7) Congestion of the kidneys both cortex and medulla;
(8) Congestion of the spleen and the pancreas in some case3 ;
(9) Severe congestion of the M. M. of the cardiac portion of the
stomach and pyloric orifice ;
(10) Congestion of the M. M. of the small intestines occasionally.
Remarks
8
From the Symptoms and
the P. M. lesions it ap-
pears reasonable to infer
that the drug causes
severe
gastro-intestinal
irritation,
asphyxiation
and congestive failure of
the right side of the heart.
Old animals appear to
survive the effects of its
toxicity while young ones
generally succumb
to
them
M. R. SUBRAMANIA SASTRY, AND OTHERS 67
after removing the extract. The results of these experiments are tabulated
in Table II
Table II
Preparation used
(a) Powdered leaves
(b) Aqueous extract of
the leaves
(c) Residue after remov-
ing the extract
No. of
dogs
fed
2
2
2
Age
Each 4
months
old
Each 5
months
old
Each 5
months
old
Dose given
per kg.
of body
weight
(in gm.)
4
3
3
Total
quantity-
fed
(in gm.)
11
11
10.5
&
10.5
Do.
Observations
Showed no devi-
ation from the
normal
Do.
Do.
The results of these experiments show that the leaves do not possess any
toxic properties.
B. The minimum lethal dose, orally
Since old dogs were found mostly to resist and survive the effects of the
toxicity, only young dogs were selected to determine its minimum lethal
dose. Eight young dogs (one old dog as control) were fed with the powdered
bulbs and the results of the experiments showed that the M. L. D. was about
1 . 75 gm. per kilogramme of body weight. Different doses were tried and the
details of the experiments are tabulated in Table III
Table III
Preparation
used
Bulbs
(dried and
powdered)
Age of the
animal
Young (below
18 months)
Young (below
12 months)
Do.
*Old (more
than
18
months)
No. of
dogs
used
1
3
4
1
9
Dose given
(in gm.)
1.5
1.6
1.75
2
Average
weight
of the
animal
(in kg.)
7
3½ to
7
4 to 7
6.5
Results
No. ended
fatally
..
1
4
5
Number
survived
1
2
..
1
4
NOTE. In the earlier stages of the investigation it was observed that in many cases
the powdered bulbs, in doses even as high as 3 to 3 .5 gm. per kg. of body weight, did
not prove lethal to animals older than 18 months [vide Table I].
68
Toxicity of Crinum defixum Ker- Gawl, I
C. The cumulative effect
(1) Bulbs. Five dogs were fed—two of them daily and the others at
regular intervals of one day, two days and three days, respectively, for varying
periods and in different doses. All the dogs succumbed. It will be interest-
ing to note, from Table IV, that a dog which was given a progressively
diminishing dose was not able to withstand, on the last day of its admin-
istration, the effects of even 5 grains—a dose much smaller than the M. L. D.
This establishes that the bulbs do exert cumulative effects.
Table IV
No. of
dogs
tried
1
1
1
2
1
No. of
times the
feeding
was
repeated
2
6
3
2
4
Dose given
5 gm. on each occasion
1st day—3 gm.
2nd day—2 gm.
3rd, 4th and 1 gm.
5th days }each day.
6th day—5 grains
10 gm. on each occasion
1st day—15 gm.
2nd day—30 gm.
20 gm. on each occasion
Interval
between
two feeds
Next day
Do. .
1 day .
2 days .
3 days .
Results
Died
Died on the
last day
of feeding
Do.
Do.
Do.
Remarks
Symptoms
of
poisoning were
exhibited
in
varying degrees
and there were
more distress-
ing symptoms
before death.
NOTE. The method of isolation of the important constituents of the bulbs and
details of the study of their pharmacological actions will be published shortly.
(2) Leaves. Although the previous experiments showed that the leaves
are not toxic, attempts were made to find out whether daily feeding of the
leaves for a fairly long period would produce any deleterious effect. With
this object, both the aqueous extract and the residue from the powdered
leaves were given to two young dogs for 11 consecutive days in doses of 4 gm.
per kilogramme of body weight. No untoward symptoms were noticed and
this shows that the leaves, besides being definitely non-toxic, have no cumula-
tive effect even on continued administration of pretty large doses over a long
period.
SUMMARY
(1) The results of feeding experiments with the bulbs and leaves of
Crinum defixum reveal that the toxicity is due to the acrid bulbs and not to
the leaves of this plant.
(2) The toxic principle (or principles) contained in the bulbs is only
partially soluble in water.
(3) The drug produces in about 15 minutes after oral administration,
severe gastro-intestinal irritation, asphyxiation and congestive failure of the
right side of the heart with petechial hæmorrhages in various internal organs.
(4) Old dogs (18 months of age and above) appear to possess the power to
resist and survive the toxic effects while young ones (up to 18 months of age)
generally succumb to them.
M. R. SUBRAMANIA SASTRY, AND OTHERS 69
(5) The minimum lethal dose of the bulbs administered orally is about
1 . 75 grammes per kg. of body weight.
(6) The bulbs have a definite cumulative action.
ACKNOWLEDGEMENTS
This work was done at the Research Unit, Medical College, Madras under
the ' Scheme for Research into the Indigenous drugs of India used in Veteri-
nary practice with special reference to their toxicology', financed by the
Imperial Council of Agricultural Research. We are highly grateful for the
financial help given by the Council.
Our thanks are due to the District Veterinary Officer, Coimbatore, and the
District Forest Officer, Coimbatore North, for the suppply of the necessary
material for this investigation and to the Government Systematic Botanist,
Coimbatore, for the identification of the plant.
We are also indebted to the Surgeon-General with the Government of
Madras for the facilities afforded and the Director of Veterinary Services,
Madras, for his direction and advice.
REFERENCE
Watt, G. (1889). Dictionary of the Economic Products of India 2, 590
TUBERCULOSIS AMONGST GOATS AT THE GOVERNMENT
CATTLE FARM, HISSAR
BY
P. N. NANDA, M.R.C.V.S.
Superintendent, Government Cattle Farm, Hissar
AND
GOPAL SINGH, L.V.P.
Veterinary Assistant Surgeon, Government Cattle Farm, Hissar
(Received for publication on 25 February 1942)
T UBERCULOSIS in goats is known to occur since 1884 [Koch] and the
first authenticated case was reported from Great Britain by Edgar
[1892]. Later, this disease was recorded in many countries by different
workers from time to time, such as by Bulling [1896], Thompson [1904] in
Saxony, Melvin [1908] in United States of America, Griffith [1917] in England,
Golden [1921] in a herd of goats imported into America from Switzerland,
Little [1924], Giescu [1924] in Cologne, Fourie [1928] in South Africa,
Schwabacher [1934], Bishop, Barnes and Reidy [1934] in America, Begley
[1938] in Ireland, Carmichael [1938] in Uganda and McKay [1939] in England.
It has also been reported from Germany by Karl Hertha cited by Calmette
[1923] and from France, by Morel cited by Celmethe [1923]. Hitherto it was
practically unknown in India, until recently when Iyer [1932] reported its
incidence in hill goats at Mukteswar. The low incidence in this country had
led to the belief that this species of animal was immune from tuberculosis.
It was probably on this assumption that Handa and Datta [1935] stated that
goats' milk was free from tubercle bacilli. A reference to the report of the
Royal Commission on Human and Animal Tuberculosis [1907], however,
indicates that goats are very susceptible to even small doses of tubercle bacilli
of bovine type.
Records available at this farm, show that until recently, no cases of tuber-
culosis in goats were detected in spite of the fact that careful post-mortem
examination was carried out as a routine practice, in every case whenever
an animal died on the farm. From 1 January 1939, to 1 August 1941,
post-mortem examinations were carried out on 5 male and 50 female goats
but in no case macroscopic tuberculous lesions were discovered. Five cases
of tuberculosis in goats have, however, recently occurred in quick succession
on this Farm. The protocols are recorded below :—
Case No. I
Female goat No. 697, Age —3 years, Breed—Beetal.
The animal was admitted in the hospital for treatment for mastitis.
It made a partial recovery, the left teat having undergone atrophy. The
70
P. N. NANDA AND GOPAL SINGH
71
animal, however, began to lose condition. On 1 August 1941, symptoms
indicative of pneumonia were noticed. There was dullness, depression and
emaciation. Appetite was suppressed and rumination suspended. Mucous
membranes of the eye and buccal cavity were anæmic. Respiration was
difficult and abdominal. There was a slight mucous discharge from the
nostrils with occasional coughing. Temperature went up to 106°F. Aus-
cultation of the chest revealed bronchial or tubular sounds on both sides and
a few patches of consolidation in the right lung were perceptible.
Blood smears were negative for bacterial and protozoon infection.
Smears prepared from the nasal discharge and stained by Ziehl-Nielsen's
stain, revealed the presence of a few diplococci only. No acid-fast bacilli
were seen.
The animal succumbed on 10 August 1941.
Post-mortem findings—
1. Miliary tuberculosis with multiple abscesses in both the lungs.
2. Enlargement and caseation of bronchial, mediastinal and some of the
mesenteric lymph glands.
3. Adhesions of the lungs with pleura and chest cavity.
4. Enlargement of supramammary lymph glands without calcification
and caseation.
5. Atrophy of the left quarter of the udder. Smears prepared from the
udder and stained with Ziehl-Nelsen's stain were negative for acid-fast
bacilli.
Acid-fast bacilli, morphologically indistinguishable from Mycobacterium
tuberculosis were, however, seen in smears from the lungs stained with Ziehl¬
Nielsen's stain.
Material preserved in 50 per cent glycerine and 10 per cent formalin
solution was sent to the Officer-in-charge, Tuberculosis and Johne's Diseases
investigation, at the Imperial Veterinary Research Institute, Mukteswar,
for biological and histopathological examination and our findings were con-
firmed by him.
Case No. II
Female goat No. 704, Age—4 years 4 months, Breed—Beetal.
The animal was admitted in the hospital on 27 July 1941, showing
respiratory trouble.
The symptoms were mostly the same as in case No. I and the goat was
being treated for pneumonia. It died during the night between 10 and 11
August 1941.
Post-mortem findings—
1. Tuberculosis of lungs with multiple abscesses.
2. Tuberculous pleurisy.
3. Some cysts of Taenia tennuicollis in the abdominal cavity.
4. Tape worm infestation in the intestines.
5. Enlargement and caseation of bronchial, mediastinal and a few of
the mesenteric lymph glands.
Acid-fast bacilli morphologically indistinguishable from Mycobacterium
tuberculosis were seen on microscopic examination of smears from the lungs.
72
Tuberculosis Amongst Goats
Case No. III
Female goat No. 806, Age—1½ years, Breed—Beetal.
The animal was admitted in the hospital for showing respiratory trouble
on 26 July 1941.
Symptoms were identical with those observed in the first two cases.
Tuberculosis was suspected and the animal was destroyed on 12 August
1941, in order to obtain fresh material for transmission to Mukteswar for
examination.
Post-mortem findings—
1. Tuberculosis of the lungs with a large abscess in the right lung.
2. Enlargement and caseation of bronchial, mediastinal and a few
mesenteric lymph glands.
Acid-fast bacilli were seen in the smears. This finding was confirmed by
the Officer-in-charge, Tuberculosis and Johne's Disease, Imperial Veterinary
Research Institute, Mukteswar.
Case No. IV
Female goat No. 526, Age—4 years 4 months, Breed—Beetal.
The animal was admitted in the hospital on 16 August 1941. Died on
the same day.
Post-mortem findings—
Sticky discharge from the nostrils. Mediastinal and bronchial lymph
glands enlarged and caseated with calcareous deposits. Both the lungs showed
multiple caseation varying from the size of a pin's head to that of a pigeon's
egg. Some cavities were seen in the pulmonary lesions, the tuberculous
material not completely filling them up. The anterior lobes of both the
lungs were pneumonic. Smears from the lung lesions showed acid-fast bacilli
morphologically indistinguishable from Mycobacterium tuberculosis.
Case No. V
Male kid No. 669, Age—1 year 9 months, Breed—Beetal.
It was received in the hospital late on 26 August 1941 evening and died
early next morning.
Post-mortem findings—
The carcass was emaciated. Abscesses in the lungs were noticed. Post-
erior mediastinal lymph gland was enlarged and there was slight caseation.
The Officer-in-charge, Tuberculosis and Johne's Disease, of the Imperial
Veterinary Research Institute, Mukteswar, who was then present at the
farm, took pieces of the affected lymph gland preserved in 10 per cent formalin
and 50 per cent glycerine for histopathological and biological examination.
Tuberculosis was later confirmed by him to be the cause.
In regard to the management of goats at the farm it may be stated that
they are grazed in the Bir (farm reserved forest) throughout the year. In
addition to this, goats in milk receive concentrates according to their milk
yield. Plenty of salt and fresh water are always at their disposal. During
winter months, due to scarcity of grass, each animal gets an extra ration of
Pala (Ziziphus nummularia). Bucks are given 1 lb. of grain daily in addition
to the generous grazing. The goats are housed in open enclosures in which
thatched shelters have been provided to protect them from rain and sun.
The enclosures are commodious and there is no overcrowding.
P. N. NANDA AND GOPAL SINGH 73
DISCUSSION
A reference to literature and the occurrence of cases of tuberculosis in
goats on this farm have afforded conclusive evidence that goats in this country-
are not immune from tuberculosis. It is difficult at this stage to attempt to
judge the incidence of and actual mortality from this disease, but it can safely
be said that tuberculosis in this country has a wider distribution than has been
hitherto supposed. The possibility of goats becoming infected from cattle
will now be a serious problem to be faced. Iyer [1932], while studying the
strains of tubercle bacilli infecting goats, reported that they are of bovine
origin. This statement is further supported by a case recorded by Griffith
[1917] where it was noticed that the goat fed on cow's milk later developed the
disease. The organism was isolated and proved to be of bovine type. The
occurrence of five cases of tuberculosis amongst goats in rapid succession
would also point to the fact that the disease was acquired from the farm cattle
in which the incidence of tuberculosis has shown a very sharp increase during
recent years. The cattle and goats at this farm graze over the same area and
thus the chances for the dissemination of disease are quite favourable. The
report received from the Imperial Veterinary Research Institute, Mukteswar
regarding the type of the organism is as follows :—
' Organism from goat No. 697 has conformed in its cultural characters
and virulence to the bovine type.'
It is of interest that tuberculosis has been recorded in a male goat also at
this farm. Previous to this, McKay [1939] recorded the disease in a male
goat. From these two cases in the male goats, there seems to be no ground
for the assumption that there is some sex resistance to the disease. It appears
that since male goats are usually slaughtered at an earlier age for meat, it
might be one of the reasons why the disease has not been recorded more
frequently.
Tuberculin testing of goats with a suitable strain of tubercle bacilli would
be of interest to the goat industry in general, but before it can be attempted,
further detailed studies on the disease are necessary. Carmichael [1938]
reports some good results with double intradermal tuberculin tests and it will
be worthwhile to try this method in India also.
SUMMARY
1. The literature on tuberculosis in goats is reviewed.
2. The occurrence of five cases of tuberculosis in goats at the Government
Cattle Farm, Hissar, is recorded in detail.
3. The tubercle bacilli responsible are of bovine type.
ACKNOWLEDGEMENTS
We desire to express our thanks to Mr Lakhshmi Sahai, M.Sc.,
M.R.C.V.S., Officer-in-charge, Tuberculosis and Johne's Disease at the
Imperial Veterinary Research Institute, Mukteswar, for his examination of
the specimens.
74
Tuberculosis Amongst Goats
REFERENCES
Begley, P. T. (1938). Vety. Rec. 50, 10, 286
Bishop, C. P., Barnes, M. F. and Reidy, T. B. (1934). J. Amer. Vet. Med. Assc. 85,
457
Bulling (1896) quoted by Carmichael (1938). Vet. Rec. 50, 36, 1147
Calmethe, A. (1923). Tubercle bacillus infection & T. B. in man and animals
Carmichael, J. (1938). Vet. Rec. 50, 36, 1147
Edgar (1892). J. Comp. Path. & Ther. 5, 80
Fourie, P. J. (1928). 13th & 14th Rep. Dir. Vet. Res. S. Afr. Pt. 1, 623
Giescu (1924) quoted by Carmichael (1938). Vet. Rec. 50, 36, 1147
Golden, G. E. (1921). Amer. Vet. J. 59, 79
Griffith, A. S. (1917). J. Path & Bact. 21, 342
Handa, B. N. and Datta, D. L. (1935). Vet. Bull. Civil Vety. Dept. Punjab. No. 6, 19
Iyer, P. R. K. (1932). Ind. J. Vet. Sci. 11, 41
Koch, R. (1884) quoted by Carmichael (1938). Vet. Rec. 50, 36, 1147
Little, W. L. (1924). Vet. J. 80, 371
Melvin (1908). 25th Ann. Rep. U. S. Bur. of Ani. Ind. 98
Royal Commission on T. B. (Human & Bov.) Sec. Inter. Rep. Pt. 1, 70 (1907)
Schwabacher, H. (1934). J. Comp. Path. & Ther. 47, 214
Thompson, (1904). 21st Ann. Rep. U. S. Bur. of Ani. Ind. 342