Ulcers have been found at times in the kidneys, but were probably secondary in origin, as other cases are reported with normal kidneys.

Faville has found in some cases amyloid degeneration. The pancreas and spleen are reported normal. The abdominal cavity may contain a slight effusion.[74] The liver has been found cirrhotic, and at times shows tubercular lesions of a secondary nature. The inner coat of the bladder has been found softened, and in sheep the bladder may be markedly distended at the autopsy. The cerebral membranes are congested and perhaps adherent,[75] and there may be blood clots over the longitudinal sinus or at the base of the brain. Effusions have been especially noted around the medulla. The arachnoid has also shown slight congestion, and in other cases the membranes showed a slight thickening. The middle ventricle was found filled with yellow serum, while the fourth ventricle contained a hemorrhagic effusion,[76] and the base of the brain was covered by a clot. The hemorrhage may become organized and the brain be held to the membranes by tough organized fibers. In many cases serous effusion is present in the lateral ventricles. The arachnoid s.p.a.ce is also in some cases similarly filled. Microscopic examination of the brain in the case of a steer showed atrophy of Purkinjie's cells.[77]

In sheep the post-mortem examination showed paleness, anaemia of the muscles, and great distention of the abdomen. The intestines were found filled with gases, and the mesenteric blood vessels filled with blood.

No peritonitis, or ascites, or ecchymoses in the mucous membranes were noted in the autopsies made on sheep by Ruedi. The liver has been seen enlarged. In sheep the brain was anaemic. Microscopically the brain showed atrophy and the Purkinjie's cells disappeared or their processes atrophied. In these sheep the brain was so anaemic that the distinction between the gray and the white matter was hard to define.[78] The membranes of the cord have been found inflamed and adherent, but the spinal cord was usually normal.[79] In some cases, however, the spinal cord has been found softened[80] and oedematous. The arteries of the limbs were gorged with blood,[81] and at the same time there was a collection of serum in the abdominal cavity. Death is thought to be due to starvation.[82] In other words, the pathological condition, according to published accounts, shows little that is characteristic save some action on the gastro-intestinal tract.

FOOTNOTES:

[71] Anderson, F. W. Poisonous Plants and the Symptoms They Produce. Bot. Gaz., vol. 14, p. 180. 1889.

[72] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p.

558. 1887.

[73] O'Brine, D. Progress Bulletin on the Loco and Larkspur.

Colo. State Agric. Coll. Bul. 25, p. 12. 1893.

[74] Faville, in O'Brine, D. Progress Bulletin on the Loco and Larkspur. Colo. State Agric. Coll. Bul. 25, p. 11. 1893.

[75] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p.

559. 1887.

[76] Stalker, M. The "Loco" Plant and Its Effect on Animals.

Bur. Animal Industry, 3d Ann. Rept. (1886), p. 274.

1887--Sayre, L. E. Loco-Weed. Amer. Pharm. a.s.soc. Proc., vol.

38, p. 108. 1890.--O'Brine, D. Progress Bulletin on the Loco and Larkspur. Colo. State Agric. Coll. Bul. 25, pp. 16, 17.

1893.

[77] Mayo, N. S., l. c., p. 118.

[78] Ruedi, C. Loco Weed (Astragalus Mollissimus): A Toxico-Chemical Study. Trans. Colo. State Med. Soc., 1895, p.

418.

[79] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p.

559. 1887.

[80] O'Brine, D. Progress Bulletin on the Loco and Larkspur.

Colo. State Agric. Coll. Bul. 25, p. 12. 1893.--Klench, J. P.

Rattleweed or Loco Disease. Amer. Vet. Rev., vol 12, p. 399.

1888.

[81] Anderson, F. W. Poisonous Plants and the Symptoms They Produce. Bot. Gaz., vol. 14, p. 180. 1889.

[82] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. and Vet. Archives, vol. 13, p. 436. 1892.

=HISTORICAL SKETCH OF LOCO INVESTIGATIONS FROM A PHARMACOLOGICAL STANDPOINT.=

During the western immigration of 1849 the Indians along the Missouri River described to the immigrants a plant (_Astragalus mollissimus_) producing death in horses and cattle, which was preceded by various forms of excitement.[83]

The attention of the United States Department of Agriculture was first called to the toxic action of the loco plants in 1873, when specimens of the plants, which were identified as _Astragalus hornii_ and _A.

lentiginosus_,[84] were sent from California by Mr. O. B. Ormsby, with the statement that they were poisonous to stock, especially to horses.

Mrs. J. S. Whipple also corroborated this information. The botanist of the Department, Dr. George Vasey,[85] published a note and requested further information concerning the plants. These notes were enlarged by a similar contribution by Dr. P. Moffat on _Aragallus lamberti_.[86] The following year Vasey reported with more fullness, and his description of the action of the plants is substantially what we find in most of the books of to-day.

In 1876 Lemmon[87] noted that _Astragalus mortoni_ was "a deadly sheep poison." At the same time Rothrock,[88] botanist of the United States Geographical Survey under Lieutenant Wheeler, described these plants, and Kellogg,[89] a botanist in California, reported that _Astragalus menziesii_ was causing great losses in horses, sheep, and cattle and claimed that the stockmen had been familiar with this disorder for at least ten or fifteen years. This report of Kellogg was followed by that of Rothrock[90] in 1877.

In 1876 a specimen of _Aragallus lamberti_ was sent from Colorado to Professor Prescott, of the University of Michigan, under the name of "crazy weed," with the statement that it was poisonous to horses and cattle and that, while the Mexicans often used it in making beer, it sometimes caused symptoms in men. His pupil, Miss Watson, undertook a study of its chemical properties. She failed to isolate any pure chemical compound, but claimed that in the root there was a body giving alkaloidal reactions and that there was also a resinous body present.

Another of his pupils, W. R. Birdsall, took the ground-up root himself in doses of 20 grains at various intervals for several days and later 40-grain doses in one and a half hours, but without experiencing any marked symptoms except colicky pains. A kitten also was given about one and a half ounces of the fluid extract without effect. Prescott[91] sums up by saying that "it would seem that the dried ground root possesses no poisonous properties." The work of Miss Watson was considered of sufficient importance to be abstracted in the Annual Report of the Commissioner of Agriculture for 1878 (1879), page 134.

Gradually the Department of Agriculture became more and more interested in this subject, and Peter Collier, chief chemist, in 1878, examined the roots and leaves of _Aragallus lamberti_ for alkaloids, but found none.[92]

In 1880 Peter Collier published a proximate a.n.a.lysis of _Astragalus mollissimus_ made by Francis A. Wentz, of Kansas. His investigations showed it to have an ash content of 6.76 per cent, while the _Aragallus lamberti_, a.n.a.lyzed by L. F. Dyrenforth, of Chicago, showed an ash content of 4.32 per cent. Collier[93] sums up by saying:

From the additional work done at this Department it seems probable that the deleterious effects observed from animals eating this plant may be due princ.i.p.ally to the fact that the sweet taste causes cattle to reject more nutritious food and strive to subsist upon the Oxytropis only. This plant is mechanically a very unfit substance for food, being of a tough, fibrous, and indigestible character. It is possible that, when the animal becomes somewhat enfeebled by lack of proper nourishment, the small amount of alkaloid may have a direct poisonous action. Again, it seems probable that the plant may contain much larger proportions of alkaloid at certain stages in its development than at others, or the seeds may prove to be the most injurious portion.

The departmental work was continued by further short notices by Vasey[94] in 1884, 1886, and 1887, and by the report of Stalker in 1887.

This report by Stalker is still the best description on the clinical side of the question.

Rothrock,[95] meeting the loco plants in his survey work, describes their effects on animals as follows:

Certain it is, however, that, once commenced, they continue it, pa.s.sing through temporary intoxication to a complete nervous and muscular wreck in the later stages, when it has developed into a fully marked disease which terminates in death from starvation or inability to digest a more nourishing food. The animal toward the last becomes stupid or wild, or even vicious, or, again, acting as though attacked with "blind staggers."

Under the name of Crotalaria, H. Gibbons,[96] in 1879, refers to a plant growing in California which it was claimed was producing characteristic symptoms of poisoning in horses and sheep. This plant Professor Maisch afterwards identified as _Aragallus lamberti_.

Dr. Isaac Ott[97] undertook the physiological study of the question and used an alcoholic extract of _Astragalus mollissimus_. He found from its action on frogs, rabbits, and cats that the plant had decided physiological action, as follows:

(1) It decreases the irritability of the motor nerves.

(2) Greatly affects the sensory ganglia of the central nervous system, preventing them from readily receiving impressions.

(3) Has a spinal tetanic action.

(4) Kills mainly by arrest of the heart.

(5) Increases the salivary secretion.

(6) Has a stupefying action on the brain.

(7) Reduces the cardiac force and frequency.

(8) Temporarily increases arterial tension, but finally decreases it.

(9) It greatly dilates the pupil.

Doctor Stockman, in England, about this time tried the action of the aqueous and alcoholic extracts of the dried _Astragalus mollissimus_ sent from Texas. He experimented with frogs and rabbits in increasing doses, but without result.[98]