Chapter IV: Part 4

[201] Christison, R. Treatise on Poisons. Edinburgh, 1845, p.
579.--Crampe. Bewährte Mittel gegen Feldmäuse. Deutsch.
Landw. Presse, vol. 5, p. 530. 1878.--Felletar, E. Fälle von
Intox. mit kohlensäur. Baryum. Pest. Med.-Chir. Presse, vol.
28, p. 1072. 1892.

[202] Husemann, T. Ein Beitrag z. Kennt. d.
Barytvergiftungen. Zeits. f. pract. Heilk., vol. 3, p. 235.
1866. In this article Husemann has collected many cases of
poisoning by barium in animals.

[203] Christison, R. Treatise on Poisons. Edinburgh, 1845, p.
579.

=BARIUM POISONING IN MAN.=

The high toxicity of barium was called attention to by early observers, but it was attributed by some to admixed arsenic. The reports of feeding experiments with barium on animals have varied markedly, but now care is being advised in the use of barium salts.[204]

Barium was introduced into medicine in the treatment of scrofula, but has fallen into disuse, and only recently attention has been called to it on account of its action on the circulatory system. Filippi,[205] however, says, "The effects on the heart and on the pressure are already the first indication of poisoning." This metal has also been used in the treatment of chronic diseases of the spinal cord, as multiple sclerosis and paralysis agitans.[206]

After the administration to a woman of 1/12 grain (0.005 gram) of barium chlorid three to five times a day for a few days, a total of 2-1/4 grains (0.135 gram), the patient developed rapid respiration, tenderness over the epigastrium, nausea, constipation, cramps in the limbs, loss of appetite, weakness, great emaciation, dysuria, some deafness with tinnitus, difficulty in speaking and thinking, with vertigo.[207] In this case the eyes were glassy, the vision indistinct, and the cheeks flushed. Kohl after the use of small doses of the same noted salivation, swelling of the gums, and falling out of the teeth, with a mercurial odor to the breath. Christison[208] states: "I have known violent vomiting, gripes, and diarrhea produced in like manner by a quantity not exceeding the usual medicinal doses." According to Kennedy few persons are able to bear 1/8 grain (0.0075 gram) of barium chlorid.[209]

In Carpenter's case after three doses of 1.6 grains (0.070 gram) of barium chlorid the patient developed almost lethal symptoms.[210] Carpenter calls attention to the drowsiness which developed in this patient after the administration of barium, a fact which had already been noted by Christison.[211]

A cartarrhal affection of various mucous membranes and a swelling of various glands have been noted, especially of the lymph and salivary glands, and in the male the testes have at times swollen.[212] The inflammation of the glands may pass on to suppuration. The skin becomes dry and shows a tendency to crack. Febrile attacks are reported after the repeated use of small doses of barium.

Scheibler[213] has called attention to the possibility of producing _chronic_ barium poisoning in man from the use of barium in the manufacture of food products.

Acute cases of poisoning in man from four or more grams of barium carbonate or chlorid or nitrate have been reported more or less frequently.[214] In the acute case of poisoning in man reported by Tiraboschi and Taito, no macroscopic changes were noted in the stomach mucosa.[215] Lopes[216] has reported one case of acute poisoning in man from less than 1 gram of barium chlorid. In this case paralysis of the limbs was a marked feature. Stern[217] cites Perondi and Lisfranc to the effect that "remarkably large doses of barium chlorid can be borne without injury by gradually increasing the doses (dissolved in much water)." Lisfranc[218] has suggested that the sensitiveness to poisoning by barium salts is greater in certain climates than in others.

No data are as yet available as to the influence of altitude and partial starvation on the toxicity of barium salts. As is well known, almost all recorded cases of locoed animals have occurred at a high altitude.

It must also be remembered that the addition of one salt to the solution of another may greatly increase the toxicity of the first one. Thus, the addition of a few milligrams of barium chlorid to a solution of a sulphocyanate renders the latter much more poisonous.[219] This may be due to the fact that the salts are more completely ionized.

* * * * *

FOOTNOTES:

[204] According to v. Jaksch, "Sie ist bei der grossen
Toxicität der Substanz immer ernst zu stellen." Vergiftungen,
1897, p. 79.

NOTE.--A thorough pharmacological study of some barium salt
is much needed, and it is hoped that the writer will be able
to complete this work.

[205] Filippi, E. Modificaz. del Ricambio Organice per Azione
del Cloruro di Bario. La Sperimentale, vol. 60, p. 610. 1906;
Sull' Azione Cardiaca del Chloruro di Bario. Archivio di
Farmacol. Speriment., vol. 5, p. 122. 1906.

[206] Schulz, H. Vorles. ü. Wirkung. u. Anwendung d.
unorganisch. Arzneistoffe. Leipzig, 1907, p. 234.--Hare, H.
A. Use of Barium Chloride in Heart Disease. Med. News, vol.
54, p. 183. 1889.

[207] Ferguson, J. C. Symptoms of Poisoning from Muriate of
Barytes. Dublin Quart. Journ. Med. Sci., vol. 1, p. 271.
1846.

[208] Christison, R., l. c., p. 580.

[209] Kennedy, H. Dose of the Muriate of Barytes. Lancet,
vol. 2, p. 28. 1873.

[210] Carpenter, J. S. Barium Choride from a Clinical
Standpoint. Med. News, vol. 59, p. 93. 1891.

[211] Christison, R., l. c., 1845, p. 578.

[212] Schulz, H. Vorles. ü. Wirkung. u. Anwendung d.
unorganisch. Arzneistoffe. Leipzig, 1907, p. 233.--Schwilgué,
C. J. A. Traité de Mat. Méd., 3 ed., vol. 1, p. 441. 1818.

NOTE.--According to the files of the Office of
Poisonous-Plant Investigations, E. D. Smith reported in the
Orange Judd Farmer, 1897, that locoed animals showed a
swelling of various glands. As yet the writer has been unable
to verify this reference.

[213] Scheibler, C. Ueber d. Verwendung giftiger Stoffe,
besonders d. Barytverbindungen bei d. Zuckerfabrication.
Chem. Zeit., vol. 11, p. 1463. 1887.

[214] Schmidt's Jahrbücher, vol. 192, p. 131. 1881.--Walsh,
J. Report of a Case of Poisoning by Chloride of Barium.
Lancet, vol. 1, p. 211. 1859.--Walch. Seltener Fall einer
tödlich. Vergiftung d. Baryta muriatica. Zeits. f.
Staatsarznk., vol. 30, p. 1. 1835.--Carpenter, J. S. Barium
Chloride from a Clinical Standpoint. Med. News, vol. 59, p.
93. 1891.--Eschricht. Dødeligt forløbende Forgiftning med
salpetersurt Baryt. Ugeskrift for Laeger, vol. 4, p. 241.
1881.--Ogler and Socquet. Empoisonnement par le Chlorure de
Baryum. Annal. d'Hyg. Publ., 3 s., vol. 25, p. 447.
1891.--Chevallier, A. Note sur un Cas d'Empoisonnement
Déterminé par l'Acétate de Baryte. Annal. d'Hyg. Publ., 2 s.,
vol. 39, p. 395. 1873.--Courtin, Cas d'Empoisonnement par du
Chlorure de Baryum. Rev. d'Hyg., vol. 4, p. 653.
1882.--Poisoning by a Baryta Compound. Pharm. Journ., 3 s.,
vol. 2, p. 1021. 1872.--Reichardt, E. Vergiftungsfall mit
kohlensäurem Baryt. Arch. d. Pharm., 3 s., vol. 4, p. 426.
1874.--Lagarde, P. Acétate de Baryte livré sous le Nom de
Sulfovinate de Soude. Union Méd., 3 s., vol. 14, p. 537.
1872.--Baum. Zwei Fälle von fahrlässiger Tödtung durch
saltpetersäures Baryt. Zeits. f. Medizinalbeamte, vol. 9, p.
759. 1896.--Funaro, A. Sul Veneficio per Sali di Bario.
L'Orosi, vol. 12, p. 397. 1894.

[215] Tiraboschi, A., and Taito, F. Avvelenamento da Bario.
Il Risveglio Medico d'Abruzzo e Molise, vol. 1, p. 171. 1906.

NOTE.--A criticism of this case is to be found in Bellisari,
G., Su Di un Presunto Avvelenamento da Bario. Il Risveglio
Medico d'Abbruzzo e Molise, vol. 2, p. 15. 1907.

[216] Lopes, A. Caso Curioso de Envenenamento Pelo Chloret de
Bario. Medicina Contempt., Lisbon, vol. 4, p. 109. 1886.

[217] Stern, E. Vergiftung mit Chlorbarium. Zeits. f.
Medizinalbeamte, vol. 9, p. 383. 1896.

NOTE.--The writer has always theoretically questioned the
danger of poisoning by loco weeds in well-fed and
well-watered animals. Compare Stalker, M., The "Loco" Plant
and Its Effect on Animals. Bur. Animal Industry, 3d Ann.
Report (1886), p. 271. 1887.

[218] Lisfranc. Leçon sur l'Emploi du Muriate de Baryte
contre les Tumeurs Blanches. Gaz. Méd. de Paris, 2 s., vol.
4, p. 215. 1836.

[219] Pauli, W., and Fröhlich, A. Pharmakodynam. Studien.
Sitz. Kaiserl. Acad. d. Wissens. z. Wien, vol. 115, III, pt.
6, p. 445. 1906.

=PATHOLOGICAL LESIONS IN EXPERIMENTAL BARIUM POISONING.=

The post-mortem examinations in cases of acute experimental barium poisoning, according to Schedel,[220] show punctiform or large hemorrhagic effusion in the fundus ventriculi[221] and in the large and small intestines, contraction of the bladder, and hemorrhage into the walls of the bladder and uterus. The heart is usually found relaxed or the left ventricle contracted in systole, while the right is relaxed. Only once were ecchymoses under the endocardium seen. The liver and kidneys showed nothing special. The urine was free from albumen and sugar. In a few cases the lungs showed some infiltration with blood. In chronic cases, according to our own investigations in rabbits, there are no characteristic macroscopic lesions, a result which agrees with Mittelstaedt's report.[222] Nothnagel and Rossbach[223] claim that in chronic poisoning by barium the peripheral nerves are altered. The same negative results have also been reported in chronic poisoning in higher animals. Reynolds[224] noted a layer like a blood clot under the cerebellum in a horse fed with barium chlorid. Fuchs[225] has called attention to the fact that the flesh of cattle poisoned with barium chlorid was harmless, perhaps owing to a conversion into an insoluble salt, a fact which may be considered in the use of locoed animals for food.

* * * * *

FOOTNOTES:

[220] Schedel, H. Beitr. z. Kennt. d. Wirkung des
Chlorbariums. 1903, p. 13.

[221] After subcutaneous injection of barium chlorid, Lewin,
by means of the spectroscope, has found barium in the stomach
walls. Lewin, L. Schicksal körperfremder chem. Stoffe im
Menschen u. besonders ihre Ausscheidung. Deutsch. Med. Woch.,
vol. 32, p. 173. 1906.

[222] Mittelstaedt, F. Ueber chronische Bariumvergiftung.
Dissert., Greifswald, 1895, p. 29.

[223] Nothnagel, H., and Rossbach, M. J. Handb. d.
Arzneimittel, p. 81. 1904.

[224] Reynolds, M. H. A Study of Certain Cathartics. Minn.
Agric. Exper. Sta., 15th Ann. Rept. 1907.

[225] Fuchs, C. J. Vergiftungsfälle durch salzsäuren Baryt
beim Rindvieh. Thierärztl. Mittheil., vol. 5, p. 159. 1870.
Fuchs suggests that further investigations on this point are
desirable. The literature of this class of experiments is
very scanty. See Fröhner and Knudsen, Einige Versuche über d.
Geniessbarkeit d. Fleisches vergift. Thiere. Monats. f.
Prakt. Thierheilk., vol. 1, p. 529. 1890.

=TOXICITY OF VARIOUS AQUEOUS EXTRACTS OF LOCO PLANTS.=

On October 21, 1907, a rabbit weighing 1,531 grams was fed with an extract of 95 grams of dried _Aragallus lamberti_ (Hugo, Colo., 1907), with an ash content of 12.44 per cent, with a barium content estimated as 2.6 milligrams of BaSO_{4} in 1 gram of ash. On the following day it weighed 1,517 grams, and the same dose was again administered. On October 23 the weight was 1,488 grams, and the dose was repeated. On the next day the weight was the same and the dose was repeated. On October 26 the weight was 1,446 grams, and again the same extract was given. On October 30 the animal weighed 1,502.5 grams; on October 31, 1,531 grams. The animal received a total extract of 475 grams of the dried plant without serious injury. This result was apparently contradictory to the earlier work.

On October 21, 1907, a rabbit weighing 1,743 grams was fed with an extract of 47.5 grams of the same dried plant. On the next day its weight was 1,729 grams, and the same amount of the extract was fed. On October 23 the weight remained the same, and the dose was repeated. On October 24 the weight was 1,658 grams, and the same amount of extract was fed. On October 26 the animal weighed 1,630 grams, when it was again fed with the same amount of extract. On October 28 the animal weighed 1,573.5 grams, but two days later the weight had risen to 1,644 grams. An extract of 237.5 grams had been administered. Here again the results appeared contradictory.

On October 21, 1907, a rabbit weighing 1,517 grams was fed with an extract of 77.5 grams. On the next day it weighed 1,545 grams, and the dose was repeated. On October 23 the animal weighed 1,531 grams, and the same amount of extract was given. On the following day it weighed 1,488 grams, and the dose was repeated. On October 26 it weighed 1,474 grams, and again the dose was repeated. On October 30 the weight had risen to 1,545 grams, and on October 31 it was 1,559 grams. This animal received in all an extract of 387.5 grams of the dried plant. An aqueous extract of 200 grams of the same in one dose also failed to produce the acute symptoms.

These feeding experiments show little of the characteristic action seen in the earlier experiments made with aqueous extracts either of the dry plant or of the fresh plant preserved with chloroform. In other words, the aqueous extract of the dried plant was only slightly poisonous, yet the plant from which the extract was made contained barium.

Of this same dried loco 200 grams were then extracted with water and digested with pepsin and finally with pancreatin in the thermostat (37.5°C.). The extract was concentrated and fed to a rabbit weighing 1,616 grams. After five hours and ten minutes the animal appeared weak in the fore legs and unable to support himself, and he died during the night. The intestines the following morning were found full of gas, the stomach red, the lungs seemed normal, and the heart was relaxed.

A rabbit weighing 1,545 grams was fed on November 15, 1907, with a preparation made in a similar manner, save that the plant was not extracted with water before digestion. On the next day it weighed 1,517 grams and on November 19, 1,361 grams. The following day the weight was 1,318 grams; on November 21, 1,233 grams, and on the next day 1,162 grams. The animal died during the night, and the autopsy was made the following morning.

The animal was greatly emaciated and the subcutaneous fat had almost all disappeared. The mesenteric vessels were dilated, but the intestines were not dilated. The peritoneal cavity was normal. The kidneys were perhaps a little injected, and measured 3 cm. in length. The lungs were normal. The left ventricle was contracted and the rest of the heart relaxed. The liver was normal and the spleen apparently normal. The stomach walls were dark, owing to decomposition. No ulcers were seen. The suprarenals were perhaps a little enlarged. The examination of the brain was negative, and no clots were found.

A similar digestion from 200 grams of the same dried plant was then ashed and the ash treated with acetic acid and freed from acid by evaporation on the bath. The ash which was insoluble in water was ground up into a fine paste and the whole was fed to a rabbit weighing 992 grams. This animal died in forty minutes, showing the characteristic symptoms seen in acute cases already described. In the autopsy the lungs and other organs seemed perfectly normal macroscopically. The stomach walls, however, were reddened and ecchymotic, and the mesenteric vessels were dilated.

On January 8, 1908, a similar digestion of the same batch was treated with a few drops of sulphuric acid to remove the barium, and the filtrate was then treated with lead carbonate to remove the sulphuric acid. After careful filtering, H_{2}S was passed into the solution and after concentration was fed in one dose on January 9, 1908, to a rabbit. The following morning the rabbit had gained in weight. On January 14 this animal weighed 30 grams more than its initial weight.

The residue of this plant after such a digestion, examined by the Hillebrand method, showed no weighable amount of barium, so that it can be seen that barium in relatively large amount was found in the plant itself, but not after the digestion. It must therefore have been the aqueous digestion which produced the characteristic symptoms. The examination of this fluid for barium might, however, be misleading, as the large amount of proteids would unquestionably interfere with the determination of this amount of barium, unprotected by other salts and silica, so that this side of the investigation was not pursued. Control feedings with an emulsion of one-half gram each of pepsin and pancreatin proved inactive.

Of the same _Aragallus lamberti_ 200 grams were similarly digested and the barium was removed with a few drops of H_{2}SO_{4}, the sulphuric acid by PbCO_{3} and a little lead acetate, and the lead by H_{2}S. Such an extract it was shown in the previous experiment would not kill. However, to this extract was added 100 milligrams of crystallized barium acetate in a solution and a precipitate formed. Nevertheless, the liquid and the precipitate were fed on February 1, 1908, to a rabbit weighing 1,304 grams. On February 3 the animal weighed 1,233 grams; on February 4, 1,176 grams; February 5, 1,120 grams; February 6, 1,006 grams; February 7, 1,219 grams; February 8, 1,219 grams; February 10, 1,304 grams.

As a control for this animal, to make sure that the loss in weight was not due to the acetic acid set free by the treatment with H_{2}S, a similar aqueous extract of the same lot of _Aragallus lamberti_ was precipitated with very much more lead acetate than in the preceding cases and also with lead subacetate and then H_{2}S. After evaporating to dryness this was fed on February 8, 1908, to a rabbit weighing 1,035 grams. On February 11 it weighed 1,021 grams; on February 13, 1,091 grams, and on February 15, 1,120 grams, showing a gain in weight.

Of the dried _Astragalus missouriensis_ (Hugo, Colo., June, 1907) 400 grams with an ash content of 21.8 per cent and which was known to contain barium (3 mg. BaSO_{4} in each 2 grams of the ash) were extracted with water and fed in four doses corresponding to 100 grams each in a period of four days. On November 18, 1907, the first day of feeding, this rabbit weighed 1,856.7 grams. Fifteen days later it weighed 1,984.3 grams.

One hundred grams of this dried plant after extraction with water were found to leave about 51.1 grams[226] of the plant undissolved. This when ashed yielded 8.2 grams of ash. Two grams of this ash yielded 5 milligrams of BaSO_{4}. In other words, the aqueous extract of the plant was inactive and the barium was found practically unextracted in the residue of the plant.

Evidently the barium in these dried plants had been converted into an insoluble form by drying or by some peculiarity of its metabolism, and was not extracted by water, but could be extracted by digesting the plants with the combined digestive ferments, pepsin and pancreatin.

Of the same dried _Astragalus missouriensis_ 200 grams were extracted with water and the extract treated with lead carbonate to remove any possible free sulphates and after filtering this was treated with H_{2}S to remove the lead. As the preceding experiment showed that the aqueous extract of this dried plant was harmless without barium, the writer decided to add barium artificially, and 100 milligrams of barium phosphate,[227] crystallized, was added to the liquid and the whole fed to a rabbit weighing 2,423.9 grams. The following morning the rabbit was found dead. The autopsy was made by Dr. H. J. Washburn, of the Bureau of Animal Industry. He found that the suprarenals were enlarged and congested, and there were small areas of hepatization at the apex of each lung. There were also acute corrosion areas on the greater curvature of the stomach and over the upper portion of the duodenum.

Of the _Astragalus missouriensis_ used in the preceding experiments, 200 grams were extracted thoroughly with water, and the extract corresponding to 100 grams, together with 80 milligrams of barium phosphate pure, was fed on March 12, 1908, to a rabbit weighing 1,261.5 grams. During this day the animal walked at times with an uncertain gait and the following morning it weighed 1,233 grams. It was then fed the rest of the solution, that is, the extract of the remaining 100 grams of the plant, but without any barium. The animal soon developed convulsions and died in a little over twenty-four hours after the original feeding. The autopsy, which was made by Dr. J. R. Mohler, of the Bureau of Animal Industry, showed that the mucous membrane of the stomach was markedly hemorrhagic and in areas gelatinous infiltration was very marked. In one portion of this hemorrhagic area there was distinct erosion. The large intestines were full of gas, the lungs were normal, the heart was relaxed, and the lungs collapsed. The blood vessels of the kidneys were markedly engorged.

Of the dried _Astragalus nitidus_ (Woodland Park, Colo., October, 1907) which was reported by the Bureau of Chemistry as containing no barium, 200 grams were extracted with water and fed in 100-gram doses for two successive days. The animal increased steadily in weight and fifteen days after the first feeding had gained 99.2 grams. This amount of the plant was also extracted with water and the residue was then digested with pepsin and pancreatin in the thermostat, as in the previous case, and fed in two doses corresponding to 100 grams each. This animal increased in weight, gaining 60 grams in six days and 165 grams in addition after a further fifteen days.

An _Astragalus mollissimus_ (Kit Carson County, Colo., December, 1906), which was also reported by the Bureau of Chemistry as containing no barium, was extracted with water, and a dose corresponding to an extract of 200 grams of the dried plant was fed in one dose without any serious result. The same amount of the dried plant was also similarly digested with pepsin and pancreatin and fed in two doses, but without the production of any symptoms, the rabbit gaining 60 grams in four days.

Of the _Aragallus lamberti_ (Hugo, Colo., June, 1907), with an ash content of 12.44 per cent, 250 grams were ashed and the ash treated with acetic acid and, after evaporating off the acetic acid, was extracted with water and the ash digested with pepsin and pancreatin. The aqueous extract and the digestion products of the ash were then fed after concentration, but without any serious effects to the animal, indicating that in this plant the barium is in a form insoluble in water and in the ashing is further changed so that it can not now be made soluble by digestion--an opposite result to the experiment in which the barium was first rendered soluble by digestion and the digestion products ashed, suggesting a possibility that plants might be found in which the barium is not extracted by digestion, at present a hypothesis.

Of dried _Astragalus decumbens_ (Ephraim, Utah, 1907), which was reported by the Bureau of Chemistry to contain no barium, 200 grams also failed to produce symptoms in rabbits by our test.

A solution containing 50 milligrams of barium acetate (crystallized) was mixed with an aqueous extract of 200 grams of the dried _Aragallus lamberti_ which had proved inactive pharmacologically, but a precipitate formed (BaSO_{4}?) and the extract still remained inactive, suggesting that the question of toxicity depended not only upon the presence of barium, but also whether other agents, such as sulphates, etc., might not be present in sufficient amount to render the barium insoluble; that is, pharmacologically inactive.

This _Aragallus lamberti_ yielded an ash content of 37.3 per cent, and the SO_{3} group was estimated at 0.27 per cent of the ash, while a corresponding lot which was obtained two years later from the same area yielded an ash content of 12.44 per cent and a SO_{3} content of 0.24 per cent of the ash.

It may be urged that the full lethal dose of the barium was not always found in the plant, yet it must be remembered that the toxic action was the resultant of the action of the total constituents and that if the barium was removed the extract was practically harmless.

In looking back over the work the most suitable preparation for producing the characteristic symptoms in rabbits seems to be the freshly ground-up plant mixed with water and preserved in chloroform, for while the dried plant might contain barium, yet the aqueous extract was often inactive, suggesting, perhaps, the presence of something in the fresh plant which aided the solution of the barium, thus accounting for the variations in toxicity of aqueous extracts made from plants dried under varying conditions. The nature of the compound in which barium exists in the plant is as yet unknown and has not been investigated. _It is important to remember that not only must barium be found in the plant to prove poisonous, but it must be in such a form that it can be extracted in the gastro-intestinal canal._

The amount of barium found in various species of loco plants will no doubt vary, and perhaps the pharmacological test on rabbits as the writer has used it may have to be modified for such plants, so that at present the wisest plan to test these plants is to determine their barium content and also make the physiological test, as has been proposed, and if the barium content runs low, say below 0.11 per cent of the ash, in plants yielding from 12 to 18 per cent of ash, then to increase the number of feedings on the rabbit. No doubt on ranges where a large number of loco plants are eaten, with little other food, plants with a very low barium content may be poisonous, but if large amounts of other food are fed the writer would expect few, if any, serious results.

As the writer's work has been confined to the laboratory side of the loco-weed investigations no feeding experiments with barium salts have been made by him on large animals. Such experiments should, of course, be made under range conditions; that is, where the water and food supply is deficient.

* * * * *

FOOTNOTES:

[226] Some was lost, being attached to the cloth used in
squeezing the extract.

[227] This barium phosphate was determined by the Bureau of
Chemistry to be BaHPO_{4} and to contain traces of iron,
sodium, and potassium, but it was free from arsenic.

=THEORETICAL ANTIDOTE FOR LOCO-WEED POISONING.=

The fact that treatment of the loco-weed extract with a few drops of sulphuric acid, which will remove the barium, renders these extracts harmless, and even apparently nutritious, would suggest the theoretical antidotal treatment to be with sulphates, in the form, perhaps, of epsom salts, but perhaps alkaline bicarbonates may be present in the stomach, either due to lessened acidity of the stomach or from drinking alkaline waters, in which case the precipitation of the barium by sulphates would presumably be interfered with, and thus the treatment be rendered ineffectual.[228] It is interesting to note that most of the remedies proposed for the successful treatment of locoed animals contain sulphates.[229]

In Storer's experiments on feeding rats with barium carbonate it was found that the barium carbonate would kill them, but if calcium carbonate was mixed with the barium the rats survived, suggesting an antidotal action. This apparent antagonism deserves further study and may lead to practical results.[230] A somewhat similar antagonism for at least a part of the action of barium has been claimed to exist between barium and potassium.[231] However, extracts of ashed plants, treated with acetic acid, which contained calcium and potassium, caused death in the experiments of the writer, but no work has yet been done by him as to the antidotal action of calcium carbonate on barium. Then, too, as Lüdeking[232] pointed out, large quantities of calcium chlorid may interfere with the precipitation of barium as a sulphate. It is well known that the presence of various salts influences the solubility of barium sulphate in water,[233] and the fact that barium has been found in solution in the urine in the presence of sulphates shows that the precipitation of barium as a sulphate in the body is not so simple as in test-tube experiments.[234] Again, in very dilute solutions, such as must necessarily occur at any one time in the stomach, the precipitate with sulphates only slowly forms and the barium may be absorbed before the insoluble compound can be formed.[235] Evidently an important point to be considered in the antidotal treatment of locoed animals with sulphates is the possibility of inducing a gastritis, with its attendant loss of weight. It therefore seems apparent that the proper treatment at present is preventive--that is, removal from the plants.

Lewin[236] has suggested the possibility of acquiring some immunity to barium, but our experiments point against the production of any practical immunity.

* * * * *

FOOTNOTES:

[228] Mendel, L. B., and Sicher, D. F., l. c., p. 148.

[229] Mayo, N. S. Some Observations upon Loco. Kans. State
Agric. Coll. Bul. 35, p. 119. 1893.

[230] Storer, F. H. Experiments on Feeding Mice with
Painter's Putty and with Other Mixtures of Pigments and Oils.
Bul. of Bussey Institute, vol. 2, p. 274. 1884.

[231] Brunton, T. L., and Cash, J. T. Contribution to Our
Knowledge of the Connection between Chemical Constitution,
Physiological Action, and Antagonism. Philos. Trans. Royal
Soc. London, I, vol. 175, p. 229. 1884.

[232] Lüdeking, C. Analyse d. Barytgruppe. Zeits. f. Anal.
Chem., vol. 29, p. 556. 1890.

[233] Fraps, G. S. Solubility of Barium Sulphate in Ferric
Chloride, Aluminum Chloride, and Magnesium Chloride. Amer.
Chem. Journ., vol. 27, p. 288. 1902.

[234] Santi has paid special attention to the solubility of
barium in the body.

[235] Fresenius, C. G. Man. of Qualitat. Chem. Anal. Tr. by
H. L. Wells, 1904, p. 148.

[236] Lewin, L. Nebenwirkungen d. Arzneimittel, 2 ed., p.
439. 1893.

=ACTION OF BARIUM ON DOMESTIC AND FARM ANIMALS.=

Barium in the form of barium chlorid has been recently introduced into veterinary therapeutics by Dieckerhoff[237] in the treatment of constipation, but Winslow[238] says that "the doses required to produce catharsis in the horse are almost toxic," and he advises against the intravenous use of this remedy.

Fröhner[239] has carefully summarized the literature on the use of barium chlorid in veterinary work, and reports that its use in the Zürich clinic has recently been so unsatisfactory that it is now seldom employed and that in the last ten years the preponderance of reports in the literature are unfavorable to the use of this agent in colic.

After the administration per os, much of the barium must be carried off in the diarrheal stools. A number of deaths in horses have been attributed to the use of this agent. No doubt the presence of sulphates, etc., derived from the food would render the barium insoluble in the gastro-intestinal tract, and this would explain the lack of poisonous action in certain of the cases in which large doses of barium proved harmless.

Husard and Biron administered daily doses of 8 grams of barium chlorid to one horse, and the same amount of barium carbonate to a second horse, for several days. A fortnight later the first horse unexpectedly died, and the second a few days later. The post-mortem examination was negative.[240] A third horse fed with barium carbonate also died suddenly. Recently barium occurring in brine has given rise to acute poisoning in stock.[241]

In a case reported by Stietenroth[242] the horse died after the injection of 0.5 gram of barium chlorid into the jugular vein. A number of sudden deaths in horses after the intravenous injection of 0.7 gram and over of barium chlorid have been collected by Fröhner.[243] The lethal dose by mouth for acute poisoning with barium chlorid in horses lies between 8 to 12 grams, while cattle require much larger doses (40 grams)[244] to induce death.

Dieckerhoff advises against the use of barium chlorid in the treatment of constipation in sheep.

After a dose of 6 grams of barium chlorid a 2-year-old healthy ram appeared perfectly well, but the following day he was depressed, refused to eat, staggered, and became so weak that he was unable to stand. The muscles of the extremities were paralyzed and the animal died. "The post-mortem examination revealed oedema of the lungs, slight cloudiness of the heart muscles, numerous small hemorrhagic spots on the mucous membrane of the small intestine, and stagnation of the blood in the vessels of the small and large intestines. Similar symptoms and lesions were found in a lamb 4 months old which was given per os 6.0 grams of barium chlorid dissolved in 200 grams of distilled water."[245]

Poisonings with barium carbonate have also been reported in pigs.[246] Domestic animals pastured in the neighborhood of barite deposits soon succumb,[247] and accidental cases of poisoning are reported in cows. Poisoning in dogs has also been reported after the subcutaneous use of this agent.[248] Linossier says that if the barium salts are used for any time the salts are deposited in various organs, largely in the kidneys, brain, and medulla, but especially in the bones.[249]

* * * * *

FOOTNOTES:

[237] Dieckerhoff. Ueber d. Wirkung d. Chlorbaryum bei
Pferden, Rindern und Schafen. Berliner Thierärztl. Woch., p.
265; see also pp. 313 and 337, 1895; Abstract In Vet. Mag.,
vol. 2, p. 360. 1895.

[238] Winslow, K. Vet. Materia Medica and Therapeutics, p.
152. 1901.

[239] Fröhner, E. Lehrb. d. Arzneimittellehre, p. 399. 1906.
Fröhner gives a detailed account of these cases.

Original note in Ehrhardt, J. Erfahrungen ü. ältere u. neue
Arzneimittel. Schweizer Archiv. f. Thierheilk., vol. 41, p.
44. 1899.

[240] Pelletier. Observations on Strontian. Journ. Nat.
Philos., vol. 1, p. 529. 1797; original in Annales de Chimie,
vol. 21, p. 127. 1797.

[241] Howard, C. D. Occurrence of Barium in the Ohio Valley
Brines and Its Relation to Stock Poisoning. W. Va. Univ.
Agric. Exper. Sta. Bul. 103. 1906.

[242] Stietenroth. Ueber Chlorbarium bei der Kolik der
Pferde. Berliner Thierärztl. Woch., p. 16. 1899.

[243] Fröhner, E. Lehrb. d. Toxikol., 2 ed., p. 116. 1901.

[244] Fröhner, E., l. c., p. 116.

See similar reports in Veterinarian, vol. 68, p. 572, 1895,
and vol. 69, p. 228, 1896; Zeits. f. Veterinärk., vol. 8, pp.
99 and 211, 1896; Nagler, F., Berliner Thierärztl. Woch., p.
65. 1896.

[245] Dieckerhoff, W. Vet. Mag., vol. 2, p. 362. 1895.

[246] Kabitz, H. Ueber d. Wirkung einiger Baryumsalze beim
Schwein. Deutsch. Thierärztl. Woch., vol. 13, p. 317. 1905.

[247] Parkes. Chem. Essays, vol. 2, p. 213. Quoted by
Christison, R., in Treatise on Poisons, Edinburgh, 4 ed., p.
581, 1845.--Fuchs, C. J. Vergiftungsfälle durch salzsäuren
Baryt beim Rindvieh. Thierärztl. Mittheil., vol. 5, pp. 133,
154. 1870.

[248] Falk. Zur Vergift. von Hunden mit Chlorbarium. Berliner
Thierärztl. Woch., p. 40. 1897.--Schirmer,
Chlorbariumvergift. beim Hunde. Berliner Thierärztl. Woch.,
vol. 23, p. 268. 1897.

[249] Linossier, G. De la Localisation du Baryum dans
l'Organisme à la Suite de l'Intoxication Chronique par un Sel
de Baryum. Comp. Rend. Hebd. Soc. de Biol., 8 s., vol. 4, p.
123. 1887.

NOTE.--Other cases of poisoning in animals may be found in
Marder, Beitrag z. Giftwirkung des Baryum chloratum. Berliner
Thierärtzl. Woch., vol. 37, p. 436. 1897; Absichtliche
Vergift. mit Chlorbarium. Zeits. f. Veterinärk., vol. 9. p.
72. 1897.

=APPLICATION OF THE RESULTS OF THESE INVESTIGATIONS TO THE RANGE.=

It has been calculated that a medium estimate of food for cattle on green fodder is about 60 pounds (30 kilos) a day.[250] Calculating this entirely in terms of _Aragallus lamberti_ and allowing 10 per cent of moisture for these plants (Sayre) would make 27 kilos of dry loco eaten by each animal per diem. In the analysis of the writer of one _Aragallus lamberti_ from Hugo, Colo., it was found to yield 12.44 per cent of ash, and the barium content corresponded to 2.6 milligrams BaSO_{4} in each gram of the ash. This would correspond to 10.24 grams of barium acetate (Ba(C_{2}H_{3}O_{2})_{2} + H_{2}O) or 9.15 grams of barium chlorid (BaCl_{2} + 2H_{2}O) per diem. This amount daily administered would, theoretically, readily produce chronic poisoning owing to the accumulation in the system, as was shown in the case of rabbits.

There is, however, some question as to whether this full theoretical amount of loco plants is eaten on the range, and the estimate has been made that one-sixth of this amount only would be actually taken. It must be remembered, as Stalker pointed out, that locoed animals develop an especial taste for these plants and after a time reject other food, so that while the number of loco plants at first taken may be small, yet later, perhaps, it is greater. A part of this barium, however, may not be taken up by the system, but may pass out undissolved. No actual experiments have yet been made with cattle by feeding small doses of the pure salt.

No doubt more of the pure barium salts will be required to produce symptoms of poisoning in animals than would be necessary in the case of the form of barium found in the plant, as in the loco-weed the barium is probably better protected from precipitation than are the barium salts when dissolved in water alone.

* * * * *

FOOTNOTES:

[250] Lane, C. B. Soiling Crop Experiments. N. J. Agric.
Exper. Sta. Bul. 158, p. 18. 1902.--Woll, F. W. One Hundred
American Rations for Dairy Cows. Univ. Wis. Agric. Exper.
Sta. Bul. 38, p. 12. 1894.--N. J. State Agric. Exper. Sta.,
20th Ann. Rept. (1899), p. 193. 1900.

CONCLUSIONS.[251]

(1) Conditions analogous to those met with in locoed animals occur in other portions of the world, especially Australia.

(2) The main symptoms described in stock on the range can be reproduced on rabbits by feeding extracts of certain loco plants. Those especially referred to here under the term "loco plants" are _Astragalus mollissimus_ and _Aragallus lamberti_.

(3) The production of chronic symptoms in rabbits is a crucial test of the pharmacological activity of these plants.

(4) The inorganic constituents, especially barium, are responsible for this action, at least in the plants collected at Hugo, Colo. Perhaps in other portions of the country other poisonous principles may be found.

(5) A close analogy exists between the clinical symptoms and pathological findings in barium poisoning and those resulting from feeding extracts of certain loco plants. Small doses of barium salts may be administered to rabbits without apparent effect, but suddenly acute symptoms set in analogous to what is reported on the range.

(6) The administration of sulphates, especially epsom salts, to form insoluble barium sulphate would be the chemical antidote which would logically be inferred from the laboratory work, but of necessity this would have to be frequently administered and its value after histological changes in the organs have occurred remains to be settled. But even the treatment of acute cases of barium poisoning in man is not always successful, even when sulphates combined with symptomatic treatment are employed. The conditions under which the sulphates fail to precipitate barium must be considered. At present it seems best to rely on preventive measures rather than on antidotal treatment.

(7) Loco plants grown on certain soils are inactive pharmacologically and contain no barium. In drying certain loco plants the barium apparently is rendered insoluble so that it is not extracted by water, but can usually be extracted by digestion with the digestive ferments.

(8) The barium to be harmful must be in such a form as to be dissolved out by digestion.

(9) In deciding whether plants are poisonous it is desirable not merely to test the aqueous or alcoholic extract, but also the extracts obtained by digesting these plants with the ferments which occur in the gastro-intestinal tract.

(10) It is important that the ash of plants, especially those grown on uncultivated soil, as on our unirrigated plains, be examined for various metals, using methods similar to those by which rocks are now analyzed in the laboratory of the United States Geological Survey.

(11) It is desirable to study various obscure chronic conditions, such as lathyrism, with a view to determine the inorganic constituents of lathyrus and other families of plants.

* * * * *

FOOTNOTES:

[251] Résumé of the results of the loco-weed investigations
carried on by the Bureau of Plant Industry was issued as
Bulletin 121, part 3, Bureau of Plant Industry, on January
28, 1908, in the form of papers by C. Dwight Marsh and Albert
C. Crawford, respectively, under the titles "Results of
Loco-Weed Investigations in the Field" and "Laboratory Work
on Loco-Weed Investigations."

INDEX.

Page.
Abortion, cows, caused by loco poisoning, 13
rabbits, caused by loco and barium poisoning, 41, 42, 62

Acid, acetic, found in loco-weed, 26

Acqua, C., reference to work, 52

Africa, South, goat disease, 17

Alfalfa, extract, experiments, 28

Alkali deposits, supposed to cause loco disease, 11

Alkaloidal reactions, loco plants, 20, 23, 27, 28

Amaranthus graecizans, supposed cause of loco disease, 10

American Pharmaceutical Association, proceedings, reference, 10

Ammonia obtained from loco plants, 26

Ammonium sulphid precipitate, effect on rabbits, 50

Anæmia, progressing, fundamental characteristic of loco disease,
16, 19

Analyses of loco plants, 21, 22, 23, 32

Anderson, F. W., references to work, 10, 12, 14, 18, 19

Animals, carnivorous and herbivorous, varying immunity to loco
disease, 23
domestic, barium poisoning, effects, 72
experiments with barium salts in laboratory, 57-62
farm, barium poisoning, effects, 72
locoed, autopsies, 18-19, 24, 26, 30, 34, 36-43, 45
clinical symptoms, 12-16
pathological conditions as described on the range,
18-19
poisoned by barium, autopsies, 57-61, 64, 67, 73, 74
young, susceptibility to loco poisoning, 15

Antelopes, susceptibility to loco disease, 12

Antidote to loco poison, theoretical, 71-72

Aragallus lamberti, ash determination, 54
barium determination, 54, 56
extracts, uses in laboratory experiments, feeding
animals, 20, 23-25, 37, 42, 44-49, 66-68, 70
properties, investigations, 20-21, 23-25, 32
spicatus, study and experiments, 33
spp., cause of loco disease, 10, 20-34
uses, medicinal and toxic properties, 35

Arsenic poisoning, references, 49

Ash determinations of loco plants, 54-55
extract from loco plants, experiments, 48-52
loco plants, barium determinations, 55-57
importance of analysis, 76

Astragalus bigelowii, extract, fatal to rabbit, 38
bisulcatus, extract fatal to rabbit, 38
decumbens, extracts, feeding experiments with rabbits, 70

Astragalus exscapus, barium reported by C. Sprengel, 53
hornii, poisonous properties, study, 19
lentiginosus, poisonous properties, study, 19
menziesii, stock poisoning, 20
missouriensis, ash content and barium determination, 56
extracts, feeding experiments with
rabbits, 68-69
mollissimus, distillate, composition, 26
extracts, experiments in feeding animals,
22, 23-25, 27-33, 36-49, 70
investigations, experiments, and
analyses, 21-34
physiological action, 22, 24-25
mortoni, a deadly sheep poison, 20
nitidus extracts, feeding experiments with rabbits, 38, 69
spp., cause of loco disease, 10, 19-34
total ash determinations, 54-55
uses, medicinal and toxic properties, 35
varieties containing no barium, 57

Australia, disease similar to loco poison, description, 16-18

Autopsies on animals after barium poisoning, 57-61, 67, 73, 74
loco poisoning,
18-19, 24, 26, 30, 34, 36-43, 45

Bachem, C., reference to work, 50

Bailey, F. M., reference to work, 17

Barium acetate, feeding experiments on animals in laboratory, 57-62
action on farm and domestic animals, 72-74
carbonate, feeding experiments on animals in laboratory, 61, 62
rats, 71
hypodermic injection, cats, fatal results, 62
chlorid, effects on human beings, 63-65
feeding experiments with animals in laboratory, 60-62
use in veterinary therapeutics, dangers, 72-73
content of rocks in Rocky Mountains, 54
determination in ash of loco plants, 54, 55-57
discovery in loco plants, feeding experiments, 5
feeding experiments with range cattle, desirability, 71
harmful when in soluble form, 76
in brine, poisoning stock, 73
well water in England, 57
insoluble after drying loco plants, extraction with digestive
ferments, 76
nitrate, feeding experiments on animals in laboratory, results,
61, 62
phosphate, analysis by Bureau of Chemistry, 69
poisoning, experimental, pathological lesions, 65
horses, sheep, and pigs, 73, 74
man, symptoms, results, 62-65
presence in certain vegetable substances, 53
salts, feeding experiments on animals in laboratory, 57-62
toxicity of different solutions, 64
relation of altitude, climate, and varying
combinations, 65
use in medicine, 62-65, 72-73
sulphate, nontoxic on account of insolubility, 53

Barrows, D. P., reference to work, 35

Bary, A., references to work, 53, 59, 60

Baum, reference to work, 64

Beech, barium present, 53

Beer, Mexico, use of "crazy weed", 20

Bellisari, G., reference to work, 64

Beryllium chlorid, effect on rabbits, 50

Binet, P., reference to work, 59

Birch, barium present, 53

Birdsall, W. R., experiments with Aragallus lamberti, 20

Blankinship, J. W., references to work, 11, 34

Blood, clots on brain, 18, 26, 37, 42, 65

Boehm, R., reference to work, 58

Böhm, C. R., reference to work, 50

Bray, W. C., reference to work, 53

Brewer, W. H., reference to work, 20

Brine, barium content, producing acute poisoning in stock, 73

Brodie, B. C., reference to work, 61

Brunton, T. L., reference to work, 72

Burgassi, G., reference to work, 52

Cæsium chlorid, experiments on rabbits, 51
occurrence in plants, toxicity, 51

Calcium acetate, experiments on rabbits, 52
carbonate, antidotal to barium, 71
experiments on rabbits, 52
occurrence in loco plants, 25, 27

Cambier, J., experiments with loco plants, 26-28

Canada, disease caused by eating ragwort, 17
freedom from loco disease, 9

Cannabis sativa, supposed cause of locoed conditions in Mexico, 10

Caprioides aureum, supposed cause of loco disease, 10

Carpenter, J. S., references to work, 63, 64

Cash, J. T., reference to work, 72

Cats, barium injection experiments, 62
loco-plant experiments, 22, 24, 30
_See also_ Kittens.

Cattle, barium feeding experiments under range conditions,
desirability, 71
daily ration of green fodder, toxic effects of loco plants, 74
loco poisoning, notes, 12, 19, 20, 22, 28
locoed, flesh harmless, 65
poisoned with barium chlorid, flesh harmless, 65
range, barium feeding experiments, desirability, 71
susceptibility to loco disease, 12

Cerium chlorid, experiments on rabbits, 50

Chemical experiments with loco plants, 46-57

Chemicals in aqueous solution, effects on rabbits, 50-52

Chemistry, Bureau, ash and barium determinations, loco plants, 54, 56

Chesnut, V. K., references to work, 10, 11, 33

Chevallier, A., reference to work, 64

Christison, R., references to work, 62, 63

Coffee substitute, use of seeds of Astragalus boeticus, 35

Collier, Peter, study of loco plants, 21

Colorado, loco disease experiments, results, 5
loss of stock from loco disease, 1898, 9

Constipation, treatment of animals with barium, danger, 73

Cotyledon ventricosa, cause of nenta, a goat disease, 17

Courtin, reference to work, 64

Cows, abortion caused by loco poisoning, 13
autopsies after loco poisoning, 18
locoed, symptoms, 25
susceptibility to loco disease, 12

Crawford, Albert C., loco investigations, reference to published
paper, 75

Crazy weed. _See_ Loco plants.

Crotalaria sagittalis, cause of loco disease, chemical
study, 10, 26-27
experiments with horses, 26-27

Curtice, C., reference to work, 31

Cyon, M., reference to work, 59

Cyprus, loco disease of cattle, sheep, and goats, 22

Darling pea, effects on horses and sheep in Australia, 16
feeding sheep, effects similar to loco poisoning, 16-17

Day, M. G., experiments with Astragalus mollissimus and Aragallus
lamberti, 15, 23-26

Delphinium spp., supposed cause of loco disease, 10

Demoussy, E., reference to work, 53

Didymium chlorid, experiments on rabbits, 51

Dieckerhoff, W., references to work, 72, 74

Digestion of loco plants, experiments, 66, 67, 68, 70

Diuretic, use of Astragalus glycophyllus, 35

Dogs, barium feeding experiments, results, 62
poisoning, subcutaneous injection, 74
loco-plant feeding experiments, 22, 23, 30, 53

Donkeys, susceptibility to loco disease, 12

Dworzak, H., reference to work, 53

Dyrenforth, reference to work, 54

Eastwood, A., references to work, 10, 12

Eckard, G. E., reference to work, 53

Ehrhardt, J., reference to work, 73

Emory, W. H., reference to work, 19

Eschricht, reference to work, 64

Experiments, laboratory, with barium salts, 57-62
loco plants, 36-56, 66-71
loco poisoning and barium feeding, results, 5

Extracts of loco plants, digestion with pepsin and pancreatin,
experiments, 66-68
testing, importance, 76
use in laboratory experiments, varying
toxicity, 36-49, 66-71

Falk, reference to work, 74

Faust, E. S., reference to work, 31

Faville, reference to work, 18

Felletar, E., reference to work, 62

Ferguson, J. C., reference to work, 63

Filippi, E., reference to work, 62

Fletcher, J., reference to work, 10

Fleurot, reference to work, 35

Folin, O., reference to work, 56

Food, use of loco plants, 35, 74

Forage, use of Astragalus nuttallianus and A. crassicarpus, 35

Forchhammer, J. G., reference to work, 53

Foster, F. B., reference to work, 26

Frankforter, G. B., reference to work, 35

Fraps, G. S., reference to work, 72

Fresenius, C. G., reference to work, 72

Fritillaria pudica, supposed cause of loco disease, 10

Frogs, loco-plant experiments, 17, 22, 24
poisoning, 17, 24

Fröhlich, A., reference to work, 65

Fröhner, E., reference to work, 73

Fuchs, C. J., references to work, 65, 74

Funaro, A., reference to work, 64

Garbanzillo, Spanish name for Astragalus mollissimus, derivation, 11

Gibbons, H., reference to work, 21

Givens, A. J., references to work, 10, 35

Glands, swelling, in locoed animals, note, 63
result of use of barium on human beings, 63

Glover, R. M., reference to work, 61

Goat disease, South Africa, note, 17

Goats, loco poisoning, 22
susceptibility to loco disease, 12

Gordon, P. R., reference to work, 17

Grass staggers, Texas loco disease, symptoms, description, 11

Greshoff, M., reference to work, 35

Guinea pig, autopsy after loco poisoning, 43
pigs, loco-plant feeding experiments, 32, 43

Guthrie, F. B., reference to work, 17

Hairs on plants cause of loco disease, suggestion, 22, 28

Hallucinations caused by loco poison, 13

Hare, H. A., reference to work, 63

Harkins, W. D., reference to work, 49

Hayes, M. H., description of Texas grass staggers, 11

Hefftner, A., reference to work, 58

Heilborn, F., reference to work, 59

Hill, J. R., reference to work, 22

Hillebrand, method of determination of barium in ash of loco
plants, 56
statement as to barium content of rocks in Rocky
Mountains, 54

Hoffmann, F., reference to work, 26

Hogs, susceptibility to loco disease, 12

Holmes, E. M., reference to work, 35

Hornberger, R., reference to work, 53

Horses, autopsies after barium poisoning, 73
loco poisoning, 18, 26
barium poisoning, 73
disease caused by feeding on Darling pea (Swainsona
galegifolia), 16
loco-plant experiments, 33
loco poisoning, notes, 16, 19, 20, 26
locoed, symptoms, 13
susceptibility to loco disease, 12

Hough, W., reference to work, 35

Howard, C. D., reference to work, 73

Hugo, Colo., soils, analysis for traces of barium, 57

Hunt, Reid, study of and experiments with loco plants, 33-34

Hurd, H. M., reference to work, 35

Husemann, T., reference to work, 62

Hydrocyanic acid, presence in loco plants, suggestion, 29

Indigo disease, similarity to loco disease, 16-17

Ingersoll, study of loco disease, 30

Injections, subcutaneous, experiments with barium salts, 62, 73, 74
loco extracts, 43

Insanity, treatment, use of Astragalus mollissimus, 35

"Insect Life," reference to work, 31

Intoxication caused by loco plants, 13, 16, 21, 22

Jaksch, J. v., references to work, 51, 62

Janvier, reference to work, 11

Kabitz, H., reference to work, 74

Kansas, loss of stock from loco disease in 1883, 9

Kellogg, A., reference to work, 19

Kelsey, F. D., reference to work, 10

Kennedy, H., reference to work, 63

Kennedy, J., experiments with loco-weed extracts, 23, 26

Kingsley, B. F., reference to work, 12

Kissner, G., reference to work, 61

Kittens, loco-plant experiments, and autopsies, 24-28
_See also_ Cats.

Kleuch, J. P., reference to work, 19

Knop, W., reference to work, 53

Knowles, M. E., references to work, 13, 14

Kobert, R., references to work, 33, 54

Laband, L., reference to work, 51

Laboratory experiments with loco plants, 36-57

Lagarde, P., reference to work, 64

Lambs, experiments in feeding loco plants, symptoms and autopsies,
31, 45, 46

Lane, C. B., reference to work, 74

Lanthanum chlorid, experiments on rabbits, 50

Lathyrism, symptoms, resemblance to loco poisoning, 15

Leucocrinum montanum, supposed cause of loco disease, 10

Lewin, L., references to work, 65, 72

Lewis, Doctor, experiments with loco plants on rabbits, 30

Linossier, G., reference to work, 74

Lisfranc, reference to work, 64

Lloyd, J. W., study of loco poison, 31, 32

Loco-acid, body supposed to be in loco plants, 30
disease, attributed to hairs on plants, 22, 28
worms, 31, 34
experiments, Colorado, results, 5
symptoms, descriptions,
11, 12-16, 17, 24, 26, 28, 29, 33, 36-44
eating habit, description, 14, 15
intoxication, 13, 16, 21, 22
investigations from a pharmacological standpoint, historical
sketch, 19-34
plants, ash determinations, 54-55
ashed, aqueous extracts, effect, 48-52
barium determinations, 55-57
eaten with large amounts of other food presumably not
dangerous, 71
effects on human beings, 15, 20, 22, 35
extracts, digestion with pepsin and pancreatin,
experiments, 66-68
extracts, variations in toxicity, 66-71
use in laboratory experiments, varying
toxicity, 36-52, 66-71
list, 10
poison, varying in carnivorous and herbivorous
animals, 23
with season, variety, and origin, 25, 48
uses as food, forage, medicine, etc., 35
without barium not poisonous, 68-71
_See also_ Loco weeds.
poison, attempts to isolate the active principle, 47
poisoning, laboratory study, results, 5-6
symptoms, 11, 12-16, 17, 24, 26, 28, 29, 33, 36-44
reproduction in rabbits, 29, 33, 36-44, 75
theoretical antidote, 71-72

Locoed animals, clinical symptoms, 12-16
pathological conditions as described on the
range, 18-19
derivation of term, 9

Locoin, experiments by Ruedi, 30

Loco-weed disease, geographical distribution, 9
family, notes on use of various members, 35
_See also_ Loco plants.

Lopes, A., reference to work, 64

Lotus americanus, supposed cause of loco disease, 10

Lüdeking, C., reference to work, 72

Lutterkorth, H., reference to work, 53

McCullaugh, F. A., references to work, 12, 13, 15, 19

McEackran, Doctor, loco-plant experiments with horse, 33

Magnesium acetate, experiments on rabbits, 52

Magnus, R., reference to work, 58

Maiden, J. H., reference to work, 16

Maisch, J. M., references to work, 21, 35

Malbec, A., reference to work, 58

Malnutrition, cause of loco disease, suggestion, 29, 34

Malvastrum coccineum, supposed cause of loco disease, 10