THEORETICAL ANTIDOTE FOR LOCO-WEED POISONING.

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 BaHPO4and to contain traces of iron, sodium, and potassium, but it was free from arsenic.

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 BaHPO4and to contain traces of iron, sodium, and potassium, but it was free from arsenic.

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.

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.

Barium in the form of barium chlorid has been recently introduced into veterinary therapeutics by Dieckerhoff[237]in the treatment ofconstipation, 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 œdema 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.

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.

[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.

[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.

[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.

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 ofAragallus lambertiand allowing 10 per cent of moisture for these plants (Sayre) would make 27 kilos of dry locoeaten by each animal per diem. In the analysis of the writer of oneAragallus lambertifrom Hugo, Colo., it was found to yield 12.44 per cent of ash, and the barium content corresponded to 2.6 milligrams BaSO4in each gram of the ash. This would correspond to 10.24 grams of barium acetate (Ba(C2H3O2)2+ H2O) or 9.15 grams of barium chlorid (BaCl2+ 2H2O) 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.

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.

(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” areAstragalus mollissimusandAragallus 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.”

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.”

Abortion, cows, caused by loco poisoning,13rabbits, caused by loco and barium poisoning,41,42,62Acid, acetic, found in loco-weed,26Acqua, C., reference to work,52Africa, South, goat disease,17Alfalfa, extract, experiments,28Alkali deposits, supposed to cause loco disease,11Alkaloidal reactions, loco plants,20,23,27,28Amaranthus graecizans, supposed cause of loco disease,10American Pharmaceutical Association, proceedings, reference,10Ammonia obtained from loco plants,26Ammonium sulphid precipitate, effect on rabbits,50Anæmia, progressing, fundamental characteristic of loco disease,16,19Analyses of loco plants,21,22,23,32Anderson, F. W., references to work,10,12,14,18,19Animals, carnivorous and herbivorous, varying immunity to loco disease,23domestic, barium poisoning, effects,72experiments with barium salts in laboratory,57-62farm, barium poisoning, effects,72locoed, autopsies,18-19,24,26,30,34,36-43,45clinical symptoms,12-16pathological conditions as described on the range,18-19poisoned by barium, autopsies,57-61,64,67,73,74young, susceptibility to loco poisoning,15Antelopes, susceptibility to loco disease,12Antidote to loco poison, theoretical,71-72Aragallus lamberti, ash determination,54barium determination,54,56extracts, uses in laboratory experiments, feeding animals,20,23-25,37,42,44-49,66-68,70properties, investigations,20-21,23-25,32spicatus, study and experiments,33spp., cause of loco disease,10,20-34uses, medicinal and toxic properties,35Arsenic poisoning, references,49Ash determinations of loco plants,54-55extract from loco plants, experiments,48-52loco plants, barium determinations,55-57importance of analysis,76Astragalus bigelowii, extract, fatal to rabbit,38bisulcatus, extract fatal to rabbit,38decumbens, extracts, feeding experiments with rabbits,70Astragalus exscapus, barium reported by C. Sprengel,53hornii, poisonous properties, study,19lentiginosus, poisonous properties, study,19menziesii, stock poisoning,20missouriensis, ash content and barium determination,56extracts, feeding experiments with rabbits,68-69mollissimus, distillate, composition,26extracts, experiments in feeding animals,22,23-25,,27-33,36-49,70investigations, experiments, and analyses,21-34physiological action,22,24-25mortoni, a deadly sheep poison,20nitidus extracts, feeding experiments with rabbits,38,69spp., cause of loco disease,10,19-34total ash determinations,54-55uses, medicinal and toxic properties,35varieties containing no barium,57Australia, disease similar to loco poison, description,16-18Autopsies on animals after barium poisoning,57-61,67,73,74loco poisoning,18-19,24,26,30,34,36-43,45

Bachem, C., reference to work,50Bailey, F. M., reference to work,17Barium acetate, feeding experiments on animals in laboratory,57-62action on farm and domestic animals,72-74carbonate, feeding experiments on animals in laboratory,61,62rats,71hypodermic injection, cats, fatal results,62chlorid, effects on human beings,63-65feeding experiments with animals in laboratory,60-62use in veterinary therapeutics, dangers,72-73content of rocks in Rocky Mountains,54determination in ash of loco plants,54,55-57discovery in loco plants, feeding experiments,5feeding experiments with range cattle, desirability,71harmful when in soluble form,76in brine, poisoning stock,73well water in England,57insoluble after drying loco plants, extraction with digestive ferments,76nitrate, feeding experiments on animals in laboratory, results,61,62phosphate, analysis by Bureau of Chemistry,69poisoning, experimental, pathological lesions,65horses, sheep, and pigs,73,74man, symptoms, results,62-65presence in certain vegetable substances,53salts, feeding experiments on animals in laboratory,57-62toxicity of different solutions,64relation of altitude, climate, and varying combinations,65use in medicine,62-65,72-73sulphate, nontoxic on account of insolubility,53Barrows, D. P., reference to work,35Bary, A., references to work,53,59,60Baum, reference to work,64Beech, barium present,53Beer, Mexico, use of “crazy weed”,20Bellisari, G., reference to work,64Beryllium chlorid, effect on rabbits,50Binet, P., reference to work,59Birch, barium present,53Birdsall, W. R., experiments with Aragallus lamberti20Blankinship, J. W., references to work,11,34Blood, clots on brain,18,26,37,42,65Boehm, R., reference to work,58Böhm, C. R., reference to work,50Bray, W. C., reference to work,53Brewer, W. H., reference to work,20Brine, barium content, producing acute poisoning in stock,73Brodie, B. C., reference to work,61Brunton, T. L., reference to work,72Burgassi, G., reference to work,52

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