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diff --git a/40256.txt b/40256.txt deleted file mode 100644 index eeb45ed..0000000 --- a/40256.txt +++ /dev/null @@ -1,5683 +0,0 @@ -The Project Gutenberg EBook of Barium, A Cause of the Loco-Weed Disease, by -Albert Cornelius Crawford - -This eBook is for the use of anyone anywhere at no cost and with -almost no restrictions whatsoever. You may copy it, give it away or -re-use it under the terms of the Project Gutenberg License included -with this eBook or online at www.gutenberg.org - - -Title: Barium, A Cause of the Loco-Weed Disease - -Author: Albert Cornelius Crawford - -Release Date: July 16, 2012 [EBook #40256] - -Language: English - -Character set encoding: ASCII - -*** START OF THIS PROJECT GUTENBERG EBOOK BARIUM *** - - - - -Produced by Pat McCoy, Bryan Ness and the Online Distributed -Proofreading Team at http://www.pgdp.net (This book was -produced from scanned images of public domain material -from the Google Print project.) - - - - - -TRANSCRIBER NOTES: - - Words in italics are indicated with an underscore (_) at the begining - and end. Words in bold are indicated with an equal sign (=) at the - begining and end. Subscripts contained in chemical notations are - indicated as _{ }. - - The table on page 32 has been modified to fit by the use of - keys to replace some of the information. - - - - - U. S. DEPARTMENT OF AGRICULTURE. - - BUREAU OF PLANT INDUSTRY--BULLETIN NO. 129. - - B. T. GALLOWAY, _Chief of Bureau_. - - - BARIUM, A CAUSE OF THE - LOCO-WEED DISEASE. - - - BY - - ALBERT C. CRAWFORD, - - PHARMACOLOGIST, POISONOUS-PLANT INVESTIGATIONS. - - - ISSUED AUGUST 22, 1908. - - [Illustration] - - - WASHINGTON: - GOVERNMENT PRINTING OFFICE. - 1908. - - - - -BUREAU OF PLANT INDUSTRY. - - - _Physiologist and Pathologist, and Chief of Bureau_, - Beverly T. Galloway. - _Physiologist and Pathologist, and Assistant Chief of Bureau_, - Albert F. Woods. - _Laboratory of Plant Pathology_, - Erwin F. Smith, Pathologist in Charge. - _Investigations of Diseases of Fruits_, - Merton B. Waite, Pathologist in Charge. - _Laboratory of Forest Pathology_, - Haven Metcalf, Pathologist in Charge. - _Cotton and Truck Diseases and Plant Disease Survey_, - William A. Orton, Pathologist in Charge. - _Plant Life History Investigations_, - Walter T. Swingle, Physiologist in Charge. - _Cotton Breeding Investigations_, - Archibald D. Shamel and Daniel N. Shoemaker, Physiologists in - Charge. - _Tobacco Investigations_, - Archibald D. Shamel, Wightman W. Garner, and Ernest H. Mathewson, - in Charge. - _Corn Investigations_, - Charles P. Hartley, Physiologist in Charge. - _Alkali and Drought Resistant Plant Breeding Investigations_, - Thomas H. Kearney, Physiologist in Charge. - _Soil Bacteriology and Water Purification Investigations_, - Karl F. Kellerman, Physiologist in Charge. - _Bionomic Investigations of Tropical and Subtropical Plants_, - Orator F. Cook, Bionomist in Charge. - _Drug and Poisonous Plant Investigations and Tea Culture - Investigations_, Rodney H. True, Physiologist in Charge. - _Physical Laboratory_, - Lyman J. Briggs, Physicist in Charge. - _Crop Technology and Fiber Plant Investigations_, - Nathan A. Cobb, Crop Technologist in Charge. - _Taxonomic and Range Investigations_, - Frederick V. Coville, Botanist in Charge. - _Farm Management Investigations_, - William J. Spillman, Agriculturist in Charge. - _Grain Investigations_, - Mark Alfred Carleton, Cerealist in Charge. - _Arlington Experimental Farm_, - Lee C. Corbett, Horticulturist in Charge. - _Vegetable Testing Gardens_, - William W. Tracy, sr., Superintendent. - _Sugar-Beet Investigations_, - Charles O. Townsend, Pathologist in Charge. - _Western Agricultural Extension Investigations_, - Carl S. Scofield, Agriculturist in Charge. - _Dry-Land Agriculture Investigations_, - E. Channing Chilcott, Agriculturist in Charge. - _Pomological Collections_, - Gustavus B. Brackett, Pomologist in Charge. - _Field Investigations in Pomology_, - William A. Taylor and G. Harold Powell, Pomologists in Charge. - _Experimental Gardens and Grounds_, - Edward N. Byrnes, Superintendent. - _Foreign Seed and Plant Introduction_, - David Fairchild, Agricultural Explorer in Charge. - _Forage Crop Investigations_, - Charles V. Piper, Agrostologist in Charge. - _Seed Laboratory_, - Edgar Brown, Botanist in Charge. - _Grain Standardization_, - John D. Shanahan, Crop Technologist in Charge. - _Subtropical Laboratory and Garden, Miami, Fla._, - Ernst A. Bessey, Pathologist in Charge. - _Plant Introduction Garden, Chico, Cal._, - W. W. Tracy, jr., Assistant Botanist in Charge. - _South Texas Garden, Brownsville, Tex._, - Edward C. Green, Pomologist in Charge. - _Farmers' Cooperative Demonstration Work_, - Seaman A. Knapp, Special Agent in Charge. - _Seed Distribution_ (Directed by Chief of Bureau), - Lisle Morrison, Assistant in General Charge. - - - _Editor_, J. E. Rockwell. - _Chief Clerk_, James E. Jones. - - - - -POISONOUS-PLANT INVESTIGATIONS. - -SCIENTIFIC STAFF. - - -Rodney H. True, _Physiologist in Charge_. - - C. Dwight Marsh, _Expert in Charge of Field Investigations_. - Albert C. Crawford, _Pharmacologist_. - Arthur B. Clawson, _Expert in Field Investigations_. - Ivar Tidestrom, _Assistant Botanist, in Cooperation with Forest - Service_. - - - - -LETTER OF TRANSMITTAL. - - - U. S. DEPARTMENT OF AGRICULTURE, - BUREAU OF PLANT INDUSTRY, - OFFICE OF THE CHIEF, - _Washington, D. C., April 10, 1908_. - - -SIR: I have the honor to transmit herewith the manuscript of a technical -bulletin entitled "Barium, a Cause of the Loco-Weed Disease," prepared -by Dr. A. C. Crawford, Pharmacologist, under the direction of Dr. Rodney -H. True, Physiologist in Charge of Poisonous-Plant Investigations, and -to recommend that it be published as Bulletin No. 129 of the series of -this Bureau. - -For many years the stockmen in many parts of the West have reported -disastrous consequences following the eating of so-called loco weeds -characteristic of the regions involved. While many have doubted any -causal relation between the plants in question and the stock losses, the -reality of the damage has remained and has seemed to require a -thoroughgoing sifting of the evidence concerning the part played by the -plants. Accordingly, in the spring of 1905 a station for the -experimental study of the problem was established at Hugo, Colo., in -charge of Dr. C. Dwight Marsh, Expert, in cooperation with the Colorado -Agricultural Experiment Station. Later a further feeding experiment was -undertaken at Imperial, Nebr., in cooperation with the Nebraska -Agricultural Experiment Station. Parallel with the feeding work in the -field, laboratory work, designed to test under laboratory conditions the -poisonous action of the plants from given areas, was undertaken at -Washington by Dr. A. C. Crawford, Pharmacologist. A further phase of his -part of the work was an attempt to ascertain the nature of such -poisonous substance or substances as might occur in the loco plants. - -In both of these lines of work Doctor Crawford has been successful, and -the technical results of his work are here collected. - -Respectfully, - - B. T. GALLOWAY, - _Chief of Bureau_. - - Hon. JAMES WILSON, - _Secretary of Agriculture_. - - - - -INTRODUCTORY STATEMENT. - - -A scientific understanding of the so-called loco-weed disease has been -demanded and sought after for several decades for most practical -purposes, but, in spite of the great amount of attention which this -problem has received, no general agreement has been found among the -results obtained. The field investigations have given such contradictory -evidence that until the Bureau of Plant Industry of the Department of -Agriculture turned its attention to the matter the whole subject of the -loco disease was regarded by many as a kind of delusion and the -existence of a distinct entity was freely doubted. Not only did this -confusion characterize the field aspect of the matter, but the situation -viewed from the standpoint of laboratory study was also much obscured. -Some investigators claimed to have separated poisonous substances of -various sorts from the loco weeds, while others of equal scientific -standing denied the presence of any poisonous substance in the plants -under general suspicion--the so-called loco weeds. - -In view of the great seriousness of the loco situation from the -standpoint of the stock interests, an active campaign both in the line -of feeding experiments in the field and laboratory study at Washington -was undertaken by the Office of Poisonous-Plant Investigations of the -Bureau of Plant Industry. - -The feeding experiments carried out at Hugo, Colo., in cooperation with -the Colorado Agricultural Experiment Station, before the close of the -first season developed evidence that there was in reality such a thing -as a loco disease. The investigator in charge was enabled to describe -the disease in its most important manifestations and made it possible to -sift the facts from the large number of contradictory statements in the -literature. - -The laboratory work, undertaken and carried on simultaneously, consisted -of a pharmacological study, under laboratory conditions and with the -usual laboratory subjects, of the action of plant material sent in from -the field. The acute phase of loco-weed poisoning, as well as a more -prolonged type of the disease, was studied. In plants found in this -preliminary feeding to be harmful, the poisonous principle was sought, -with the very striking results fully described in this paper. The -demonstration of the presence of barium in the plants was followed by -barium feeding, with the production of symptoms which agreed with those -produced in the laboratory with loco extracts and in the field -experiments with the loco plants as seen growing on the range. By -comparing these laboratory results with those produced in connection -with the field work, it became possible to sift the wheat from the chaff -in the mass of contradictory evidence detailed in the literature of this -subject. - -The practical importance of the discovery of the true nature of the -active poisonous principle of the loco weeds is very great. It not only -sheds light on the loco situation and enables one to explain many -hitherto inexplicable things, but it also adds much to our knowledge of -barium in its medical bearings. It opens up most important problems -concerning the soils and the relation of the flora to them. It should be -borne in mind that although barium is shown to be chiefly responsible -for the poisonous properties of loco weeds in eastern Colorado, it is -entirely possible that in other regions other substances may be equally -or even more significant. This discovery also seems likely to provide a -basis for a rational treatment of locoed stock. Unfortunately, the -discovery of the fact that barium is the poisonous constituent of loco -weeds came too late to aid in the search for remedial measures on the -range during the period covered by this report, but those empirically -arrived at have received additional support from these laboratory -results. - -Thus the work in field and laboratory, undertaken after repeated -attempts and discouraging failures by others, has yielded results to -persistent scientific research and promises practical aid to the now -suffering live-stock interests. The results of the laboratory work are -presented in this bulletin. - - - RODNEY H. TRUE, - _Physiologist in Charge_. - - - - -CONTENTS. - - Page. - - Geographical distribution of the loco-weed disease and - allied conditions 9 - - Plants associated with the locoed condition 10 - - Clinical symptoms of locoed animals as described in literature 12 - - Conditions similar to loco-weed poisoning in other parts - of the world 16 - - Pathological conditions in locoed animals as described on - the range 18 - - Historical sketch of loco investigations from a pharmacological - standpoint 19 - - Notes on various members of the loco-weed family 35 - - Laboratory experiments--physiological 36 - - Experiments on rabbits 36 - - Acute cases 36 - - Chronic cases 38 - - Pregnant animals 42 - - Subcutaneous injections 43 - - Summary of feeding experiments on rabbits 44 - - Experiments on sheep 44 - - Laboratory experiments--chemical 46 - - Effect of the aqueous extract of ashed loco plants 49 - - Total ash determinations of loco plants 54 - - Barium determinations in the ash of loco plants 55 - - Analysis of soils 57 - - Feeding experiments with barium salts on animals in the - laboratory 57 - - Barium poisoning in man 62 - - Pathological lesions in experimental barium poisoning 65 - - Toxicity of various aqueous extracts of loco plants 66 - - Theoretical antidote for loco-weed poisoning 71 - - Action of barium on domestic and farm animals 72 - - Application of the results of these investigations to - the range 74 - - Conclusions 75 - - Index 77 - - - - - BARIUM, A CAUSE OF THE LOCO-WEED - DISEASE. - - - - -=GEOGRAPHICAL DISTRIBUTION OF THE LOCO-WEED DISEASE AND ALLIED -CONDITIONS.= - - -In our Western States there is a marked annual loss of stock due to -various causes. Some of these animals die in a condition known as -"locoed," a term derived from the Spanish word "loco," meaning foolish -or crazy. - -This disorder extends from Montana to Texas and Mexico, and from Kansas -and Nebraska to California.[1] - -In 1898 the United States Department of Agriculture sent out, under the -immediate direction of Mr. V. K. Chesnut, a request for information -concerning the ravages of the loco disease. It was found that in the ten -States of California, Colorado, Kansas, Montana, Nebraska, New Mexico, -North Dakota, Oklahoma, Texas, and Wyoming the loss in 1898 was -$144,850. Of this amount, $117,300 was attributed to Colorado alone; in -fact, the disorder spread so that this State expended more than $200,000 -in two years and over $425,000 in a period of nine years in attempts to -eradicate the loco plants, the supposed cause of the trouble.[2] - -The loss in one area of 35 by 120 miles in southwestern Kansas amounted -to 25,000 cattle in 1883.[3] This loss in stock has been so great that -the raising of horses has of necessity been abandoned in certain areas -on account of the prevalence of these loco weeds. - -It is difficult to obtain accurate data, as the ranchmen believe that -any information as to the prevalence of the disorder would interfere -with the value of their stock.[4] - -Dr. James Fletcher, of the Central Experimental Farm, Ottawa, Canada, -testified before the Select Standing Committee on Agriculture and -Colonization that he had never seen a case in the North-west of a -Canadian bred animal being locoed, although the loco plants were -prevalent. He explained this absence of loco disease by the abundance of -grass on the range, because of which the animals do not acquire the -habit of eating loco plants.[5] Cases have been reported, however, in -Manitoba.[6] - - * * * * * - -FOOTNOTES: - - [1] Stalker, M. The "Loco" Plant and Its Effect on Animals. - Bur. Animal Industry, 3d Ann. Rept. (1886), p. 271. 1887. - - [2] Bur. Animal Industry, 6th and 7th Ann. Repts. (1889 and - 1890), p. 272. 1891. - - [3] Day, M. G. Loco-Weed. In F. P. Foster's Reference-Book of - Practical Therapeutics, vol. 1, p. 587. 1896. - - [4] O'Brine, D. Progress Bulletin on the Loco and Larkspur. - Colo. State Agric. Coll. Bul. 25, p. 18. 1893. - - [5] Fletcher, J. Evidence Before the Select Standing - Comminttee on Agriculture and Colonization. Ottawas, 1905, p. - 53. - - [6] Fletcher, J. Experimental Farms Reports for 1892, p. 148. - 1893. - - - - -=PLANTS ASSOCIATED WITH THE LOCOED CONDITION.= - - -The condition known as "locoed" is popularly believed to be due to -eating various plants, especially the members of the Astragalus and -Aragallus genera of the Leguminosae, or pea family, but particularly to -_Astragalus mollissimus_ and _Aragallus lamberti_. These plants have -therefore received the name "loco plants,"[7] or crazy weed. But others, -as _Astragalus mortoni_,[8] _A. hornii_, _A. lentiginosus_, _A. -pattersoni_,[9] _A. nuttallianus_, _A. missouriensis_, _A. lotifloras_, -_A. bisulcatus_, _A. haydenianus_,[10] _A. tridactylicus_,[11] -_Crotalaria sagittalis_, _Lotus americanus_,[12] _Sophora sericea_, -_Caprioides aureum_, _Aragallus deflexa_,[13] _A. campestris_,[14] _A. -lagopus_,[15] _Malvastrum coccineum_, _Amaranthus graecizans_, and -_Rhamnus lanceolata_, are considered by some as loco plants.[16] In -other places _Stipa vaseyi_, _Leucocrinum montanum_, _Fritillaria -pudica_, _Zygadenus elegans_,[17] and even species of Delphinium are -considered loco plants, so widely has this name been used. - -In Mexico the term "locoed" embraces a condition due to the action of -_Cannabis sativa_ and various members of the nightshade family. This -term has been much abused and has been made to embrace many groups of -symptoms. In fact, if an animal dies while showing more or less stupor -it is said to be locoed.[18] The early Spanish settlers seemed to be -unfamiliar with the disease, or at least of any causative relation -between the plant and the disease. The Spanish name for _Astragalus -mollissimus_ was "Garbanzillo," from its resemblance to Garbanzo (_Cicer -arietinum_), which is used in Spain as a food.[19] The term as applied -to this condition seems to be of comparatively recent origin.[20] - -A somewhat similar condition to the loco in stock is sometimes -attributed by the ranchmen of our Western States to eating various -sages.[21] In Texas the loco disease is known as "grass staggers."[22] - -Hayes[23] has described as follows a condition known as grass staggers, -which apparently has little resemblance to loco and is supposed to be -due to eating overripe grass, especially rye. - - The symptoms, generally, take two or three days to become - developed. The animal gradually becomes more or less unconscious - and paralyzed and staggers if forced to walk. Although he may have - great difficulty in keeping on his legs, he is extremely averse - from going down and leans for support against any convenient - object. He breathes in a snoring manner. The mucous membranes are - tinged with yellow. Convulsions, or spasms, like those of tetanus, - may come on. - - Recovery may be expected in cases which are not marked by extreme - symptoms. - -If animals are not regularly salted, they visit salt deposits and eat -the alkalis. This some sheepmen believe to be the cause of the locoed -condition, but this is disproved by the occurrence of locoed animals in -ranges without salt. Others modify this view by claiming that the -vitiation in taste from eating these alkalis leads to a desire for the -loco weeds and thus to the locoed condition.[24] - - * * * * * - -FOOTNOTES: - - [5] Fletcher, J. Evidence Before the Select Standing - Committee on Agriculture and Colonization. Ottawa, 1905, p. - 53. - - [7] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p. 555. - 1887.--Stalker, M. The "Loco" Plant and Its Effect on - Animals. Bur. Animal Industry, 3d Ann. Report. (1886), p. - 271. 1887. - - [8] Eastwood, A. The Loco Weeds. Zoe, vol. 3, p. 53. 1892. - - [9] Chesnut, V. K. Preliminary Catalogue of Plants Poisonous - to Stock. Bur. Animal Industry, 15th Ann. Rept. (1898), p. - 404. - - [10] Williams, T. A. Some Plants Injurious to Stock. S. Dak. - Agric. Coll. and Exper. Sta. Bul. 33, p. 21. 1893. - - [11] Givens, A. J. Loco or Crazy Weed. Med. Century, vol. 1, - p. 22. 1893. - - [12] Eastwood, A., l. c. 1892. - - [13] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p. - 555. 1887. - - [14] Amer. Pharm. Assoc. Proc. for 1879, vol. 27, p. 611. - 1880. - - [15] Kelsey, F. D. Another Loco Plant. Bot. Gaz., vol. 14, p. - 20. 1889. - - [16] Sayre, L. E. Loco Weed. Kans. State Board Agric., 5th - Bienn. Rept., p. 209. 1887. - - [17] Anderson, F. W. Poisonous Plants and the Symptoms They - Produce. Bot. Gaz., vol. 14, p. 180. 1889.--Pammel, L. H. - Loco Weeds. Vis Medicatrix, vol. 1, p. 44. 1891. - - [18] Stalker, M. The "Loco" Plant and Its Effect on Animals. - Bur. Animal Industry, 3d Ann. Rept. (1886), p. 275. - 1887.--Anderson, F. W. Poisonous Plants and the Symptoms They - Produce. Bot. Gaz., vol. 14, p. 180. 1889. - - NOTE.--The symptoms described in Janvier's interesting story, - "In Old Mexico" (Scribner's Magazine, vol. 1, p. 67, 1887), - would coincide with those due to some member of the - nightshade family (probably _Datura stramonium_). See also - Pilgrim, C. W., Does the Loco Weed Produce Insanity? in Proc. - Amer. Medico-Psycholog. Assoc., vol. 5, p. 167. 1898. - - [19] Sayre, L. E. Loco Weed. Kans. State Board Agric., 5th - Bienn. Rept., p. 209. 1887. - - [20] Stalker, M. The "Loco" Plant and Its Effect on Animals. - Bur. Animal Industry, 3d Ann. Rept. (1886), p. 272. 1887. - - [21] Mayo, N. S. Loco. The Industrialist, vol. 30, p. 473. - 1904. - - [22] Science, vol. 9, p. 32. 1887. - - [23] Hayes, M. H. Veterinary Notes for Horse Owners, London, - 1903, p. 425.--Compare Woronin, M. Ueber die Taumelgetreide - in Sued-Ussurien. Bot. Zeit., vol. 49, p. 80. 1891. - - [24] Chesnut, V. K., and Wilcox, E. V. Stock-Poisoning Plants - of Montana. U. S. Dept. Agric., Div. Bot., Bul. 26, p. 88. - 1901. - - NOTE.--The wide distribution of these plants is claimed to be - partly due to the buffalo. See Blankinship, J. W., The Loco - and Some Other Poisonous Plants in Montana, in Mont. Agric. - Exper. Sta. Bul. 45, p. 79. 1903. - - - - -=CLINICAL SYMPTOMS OF LOCOED ANIMALS AS DESCRIBED IN LITERATURE.= - - -The animals usually affected are sheep, horses, cattle, mules,[25] -donkeys,[26] and goats. It is claimed that practically all herbivorous -animals are liable to the disease, even antelopes being affected.[27] -Hogs are said to be unaffected,[28] but definite information is lacking. -Cows seem to be less sensitive to this form of intoxication.[29] The -condition is usually a chronic one, although acute cases are said to -occur at times. The symptoms consist of digestive disturbances, -associated with emaciation and various symptoms suggesting lesions in -the nervous system, central or peripheral. The animals lose their -appetite from the first, begin to emaciate, and show symptoms of -malnutrition and starvation. The head trembles, the gait becomes feeble -and uncertain, the eyes become sunken and have a "flat, glassy -look."[30] There is a general sluggishness, muscular incoordination, and -difficulty in motion; finally all control of the limbs is lost and the -animal is unable to stand; the coat becomes rough and loses its luster, -and, in fact, all the typical symptoms of starvation appear. In some -cases diarrhea is also present. - -All of Nockolds's animals, however, were constipated and the stools were -covered with mucus.[31] The dependent portions of the body may swell, -simply as an expression of the anaemia.[32] Sometimes there are symptoms -indicating acute pain,[33] the animals running about as if affected with -colic. They may belch and their abdomens swell. Some claim that the -animals are markedly salivated so that the saliva trickles from their -mouths. In other cases the mouth may be dry.[34] The eyes may be rolled -up so that the whites alone show. In some cases the pupil has been noted -to be dilated, as in atropine poisoning,[35] but Wilcox states that -they are contracted as after the use of eserine.[36] The temperature of -the animal falls from 1/2 degree to 1-1/2 degrees F. below normal.[37] -Tetanic symptoms may occur,[38] or the muscles of the mouth and tongue -becoming paralyzed may interfere with mastication. When water is offered -to the animal, it gazes stupidly at it and may not drink for days. One -of the symptoms noted is the loss of power to back properly.[39] Cows -during the first two or three months of gestation are almost sure to -abort.[40] This is claimed by Knowles, however, to be due to -malnutrition. As a result of these observations, suggesting some uterine -action, the drug has been proposed as an emmenagogue.[41] - -The psychical symptoms are shown by errors of judgment. The animal -becomes dull and spiritless and wanders about half dazed. The mental -dullness passes into stupor. This dull, stupid condition has been -compared to intoxication with opium. If the locoed horse is led across a -stick lying on the ground he often jumps high as if it were a great -obstacle. The animal may now have maniacal attacks, during which he -rears and may fall backward,[42] and makes unreasonable jumps and other -unexpected movements, thus rendering himself dangerous to man.[43] Other -symptoms due to disturbances of the central nervous system are -hallucinations of various sorts. Though the optic nerve itself is -apparently not affected, the animal will stare at an object for a long -time without any apparent comprehension of its nature. This disturbance -in the visual function McCullaugh claims to be one of the first symptoms -of this disease. The animal seems to lose all idea of distance, as he -will butt against an obstruction as if oblivious of its presence. Any -sudden or violent motion made before him may cause him to fall. -According to some, the animal loses the sense which guides him in -finding water. A cow may fail to recognize her calf.[44] There is more -or less loss of control of the limbs[45] and tremors;[46] the feet are -lifted abnormally high when trotting, and, if crowded, the animal falls -headlong and will jump over little hollows as if they were wide -ditches.[47] The horse may shy without apparent cause and kick at -imaginary objects,[48] and, in fact, the reasoning powers seem to be -lost. These attacks are brought on by sudden excitement or when crossing -water.[49] There may be cutaneous hyperaesthesia. - -The animals may remain with the herd, but they often wander away. -Stalker records the following observations: - - I have seen a single animal miles away from any other individual of - the herd, carefully searching as if for some lost object, and when - a loco plant is found he would devour every morsel of it with the - greatest relish. As soon as one plant was eaten he would - immediately go in search of more, apparently oblivious to - everything but the intoxication afforded by his one favorite - article of food.[50] - -All of Nockolds's animals which were locoed were mares more than 6 years -of age.[51] - -According to Stalker there is a passive type in which the animal shows -symptoms only on being disturbed; the animal then becomes unmanageable. -This happens even with old, well-broken saddle horses.[52] - -There are few published reports as to the symptoms occurring in sheep -which are locoed. Stalker[53] says sheep "become loco-eaters, grow -stupid, emaciated, and eventually die." One of the few descriptions of -the symptoms is that of Ruedi,[54] in which he claims that the symptoms -in sheep are those comparable to the symptoms of cerebro-spinal -meningitis except that there is an absence of fever. Ruedi speaks of -sheep "lying flat on the ground, not able to stand, and not able even to -lift their heads to drink the offered water; the head and the vertebra -in opisthotonus position; the four legs stretched out and stiff; -breathing was stertorous, pulse slow, abdomen much distended, diarrhea -present. * * * The heart * * * was very slow and insufficient." The -teeth (in sheep) may blacken and fall out.[55] - -It is mainly the young animals, such as lambs and colts, that are -affected, probably due to the fact that their attention is more easily -directed to the flower of the loco[56] plants. It is claimed (on slight -evidence) that men have become locoed. The symptoms in them are nausea -and headache.[57] - -Schuchardt[58] has called attention to the resemblance of the symptoms -in locoed animals to those which occur in so-called lathyrism, but most -observers in this country have especially marked the resemblance of the -symptoms to those induced by the habitual use of narcotic drugs.[59] - -As a rule the loco plants are refused by animals save when there is lack -of other food, although at times animals have shown the keenest relish -for these plants, rejected all other forage, and devoted their whole -attention to searching for the loco plants.[60] - -Stalker says that animals not too long addicted to the use of these -plants, if confined, soon lose their taste for them (after two or three -months),[61] although old loco eaters do not readily lose the habit. -Stalker also says that "it is to be presumed that the plant is possessed -of some toxic property that has a specific effect on the nervous -centers, and that these effects have a marked tendency to remain -permanent."[62] - -The fundamental character of the disorder seems to be a progressing -anaemia. The interpretation of psychical symptoms in herbivora, and -especially on the range, must often be fallacious. - - * * * * * - -FOOTNOTES: - - [25] Kingsley, B. F. The Loco Plant. Daniel's Texas Medical - Journal, vol. 3, p. 522. 1888. - - [26] Schwartzkopff, O. The Effects of "Loco-Weed." Amer. Vet. - Rev., vol. 12, p. 162. 1888. - - [27] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. & - Vet. Archives, vol. 13, p. 435. 1892. - - [28] Eastwood, A. The Loco Weeds. Zoe, vol. 3, p. 57. 1892. - - [29] Vasey, G. Plants Poisonous to Cattle in California. - Report of Commissioner of Agriculture for 1874, p. 159. 1875. - - [30] Vasey, G., l. c., p. 159. - - [31] Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev., - vol. 20, p. 570. 1896-7. - - [32] Patterson, A. H. Starvation OEdema. Med. Rev., vol. - 56, p. 715, 1899. - - [33] Vasey, G. Botanical Notes, Monthly Reports of Dept. - Agriculture for 1873, p. 504. 1874. - - [34] Anderson, F. W. Poisonous Plants and the Symptoms They - Produce. Bot. Gaz., vol. 14, p. 180. 1889. - - [35] Schwartzkopff, O. The Effects of "Loco-Weed." Amer. Vet. - Rev., vol. 12, p. 161. 1888. - - [36] Wilcox, T. E. Treatment of "Loco" Poisoning in Idaho - Territory. Med. Rec., vol. 31, p. 268. 1887. - - [37] Mayo, N. S. Some Observations Upon Loco. Kans. State - Agric. Coll. Bul. 35, p. 118. 1893. - - [38] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. and - Vet. Archives, vol. 13, p. 436. 1892. - - [39] O'Brine, D. Progress Bulletin on the Loco and Larkspur. - Colo. State Agric. Coll. Bul. 25, p. 12. 1893. - - [40] Knowles, M. E. Loco Poisoning. Breeders' Gaz., vol. 39, - p. 973. 1901.--Sayre, L. E. Loco Weed. Kans. State Board of - Agric., 5th Bienn. Rept., p. 211. 1887.--Ruedi, C. Loco Weed. - Trans. Colo. State Med. Soc., p. 422. 1895. - - [41] Miller, C. H. The Loco Weed: Its Probable Usefulness as - an Emmenagogue. Southern Clinic, vol. 11, p. 269. 1888. - - [42] Vasey, G. Botanical Notes. Monthly Reports of Dept. - Agriculture for 1873, p. 504. 1874. - - [43] Parker, W. T. The Loco-Weed. Science, vol. 23, p. 101. - 1894. - - [44] Vasey, G. Botanical Notes. Monthly Reports of Dept. - Agriculture for 1874, p. 513. 1875. - - [45] Anderson, F. W. Poisonous Plants and the Symptoms They - Produce. Bot. Gaz., vol. 14, p. 180. 1889. - - [46] Sayre, L. E. Loco Weed. Proc. Amer. Pharm. Assoc., vol. - 36, p. 111. 1888. - - [47] Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev., - vol. 20, p. 570. 1896-7. - - [48] Knowles, M. E. Loco Poisoning. Breeders' Gaz., vol. 39, - p. 972. 1901. - - [49] Vasey, G. Botanical Notes. Monthly Reports of Dept. - Agriculture for 1873, p. 504. 1874. - - [50] Stalker, M. The "Loco" Plant and Its Effect on Animals. - Bur. Animal Industry, 3d Ann. Rept. (1886), p. 272. - 1887.--Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev., - vol. 20, p. 570. 1896-7.--Maisch, J. M. Poisonous Species of - Astragalus. Amer. Journ. Pharm., vol. 51, p. 239. 1879. - - [51] Nockolds, C. Poisoning by Loco Weed. Amer. Vet. Rev., - vol. 20, p. 570. 1896-7. - - [52] Stalker, M., l. c., p. 273. - - [53] Stalker, M., l. c., p. 274. - - [54] Ruedi, C. Loco Weed (Astragalus Mollissimus): A - Toxico-Chemical Study. Trans. Colo. State Med. Soc., 1895, p. - 417. - - [55] Blankinship, J. W. Loco and Some Other Poisonous Plants - in Montana. Mont. Agric. Exper. Sta. Bul. 45, p. 81. 1903. - - [56] Blankinship, J. W., l. c. - - [57] Day, M. G. Loco-Weed. In F. P. Foster's Reference Book - of Practical Therapeutics, vol. 1, p. 588. 1896.--Pilgrim, C. - W. Does the Loco-Weed Produce Insanity? Proc. Amer. - Medico-Psycholog. Assoc., vol. 5, p. 167. 1898. - - [58] Schuchardt, B. Die Loco-Krankheit der Pferde und des - Rindviehs. Deutsch. Zeits. f. Thiermed., vol. 18, p. 405. - 1892.--Parker, W. T. Loco-Weed. Science, vol. 23, p. 101. - 1894. - - [59] McCullaugh, F. A. Locoed Horses. Journ. Comp. Med. and - Vet. Archives, vol. 13, p. 435. 1892. - - [60] Stalker, M. The "Loco" Plant and Its Effect on Animals. - Bur. Animal Industry, 3d Ann. Rept. (1886), p. 272. 1887. - - [61] Stalker, M. The "Loco" Plant and Its Effect on Animals. - Bur. Animal Industry, 3d Ann. Rept. (1886), p. 272. - 1887.--See also Linfield, F. B. Sheep Feeding, in Mont. - Agric. Coll. Exper. Sta. Bul., 59. 1905.--Special Report on - Diseases of Cattle. Bur. Animal Industry, 1904, p. - 66.--Wilcox, E. V. Plant Poisoning of Stock in Montana. Bur. - Animal Industry, 17th Ann. Rept., p. 115. 1900. - - [62] Stalker, M., l. c., p. 275. - - - - -=CONDITIONS SIMILAR TO LOCO-WEED POISONING IN OTHER PARTS OF THE WORLD.= - - -According to Maiden[63] a condition similar to loco is met with among -animals in Australia and is there believed to be due to eating various -species of Swainsona.[64] As Maiden says, "Its effect on sheep is well -known; they separate from the flock, wander about listlessly, and are -known to the shepherds as 'pea-eaters' or 'indigo-eaters.' When once a -sheep takes to eating this plant it seldom or never fattens, and may be -said to be lost to its owner." Horses, after eating this herb, "were -exceptionally difficult to catch, and it was observed how strange they -appeared. Their eyes were staring out of their heads and they were -prancing against trees and stumps. The second day two out of nine died, -and five others had to be left at the camp." - -Martin[65] experimentally studied these cases of intoxication and sums -up his work as follows: - - 1. That one can by feeding sheep upon Darling pea reproduce all the - symptoms which are attributed by pastoralists to this cause. - Briefly stated these symptoms are: Stupidity, loss of alertness and - an agonized expression, followed by stiffness and slight staggering - and frequently trembling of the head or limbs. Later, clumsiness - and unsteadiness ensue, which slowly advance until the animal often - falls down. In this stage, the action of the animal in running over - small obstacles is characteristic. It jumps over a twig as if it - were a foot in height. When first it commences to tumble about, it - is able more or less readily to regain its feet, but in the - advanced stage of the disease this is impossible and, after - exhausting itself in efforts to do so, it remains lying down until - it dies. During the whole time the sheep become progressively more - bloodless, and in advanced cases the blood when shed appears to the - naked eye lighter in color. It contains fewer red blood-cells - (about two-thirds to one-half the usual number). (The corpuscles - were estimated in several cases by means of a haemocytometer.) All - these symptoms are much aggravated by driving. Thus, an animal in - which the symptoms are little marked may exhibit them in a striking - degree after being driven. In addition to the above the teeth - (especially in young sheep) frequently become loose, and - consequently displaced or even dislodged. - - 2. That the time which elapses before the onset of definite - symptoms is three to four weeks in sheep of 2 to 3 years old. (It - is probable, however, that with younger animals the time is - shorter.) - - 3. That under the conditions of the experiment, the animals - survived about three months. They lived, however, an invalid's - life. Everything was brought to them, and it is improbable that if - feeding exclusively upon the pea, and left to shift for themselves - in the paddocks, they would survive more than two months. - - 4. That if a sheep be returned to proper fodder after one month to - six weeks feeding upon the pea, and before the symptoms are fully - established, it may recover completely. - - 5. That when once the paralytic symptoms are established it will - not recover; but if returned to proper food, will remain in much - the same condition, becoming neither better nor worse. - - 6. That Darling pea contains a very fair amount of nourishing - material so that animals may, provided they eat it readily, retain - their condition on it for some weeks, until the poisonous principle - contained has had time to exert its effects. - -These plants, if fed with other herbage, do not seem to be injurious and -apparently lose their harmful action upon being cultivated.[66] As long -as salt is properly fed the animals will not eat this plant[67] and are -said to suffer no effects from it. Physiological study has shown the -presence of a body with marked sudorific power which causes rapid -emaciation in frogs.[68] - -It has been claimed that these symptoms are due to the presence of a -narcotic poison in the plant.[69] Post-mortem examinations were negative -save for the presence of a peripheral neuritis.[70] - - * * * * * - -FOOTNOTES: - - [63] Maiden, J. H. Plants Reputed to be Poisonous to Stock in - Australia. Dept. Agric., New South Wales, Misc. Pub. No. 477, - pp. 15, 16. 1901. - - [64] Notes on Some American and Australian Plants Injurious - to Stock. Agric. Gaz., New South Wales, vol. 4, p. 677. - 1894.--Notes on Weeds. The Darling Pea. Agric. Gaz., New - South Wales, vol. 3, p. 330. 1893. - - [65] Martin, C. J. Report on an Investigation into the - Effects of Darling Pea (Swainsona Galegifolia) upon Sheep. - Agric. Gaz., New South Wales, vol. 8, p. 366. 1898. - - [66] Woolls, W. On the Forage-Plants Indigenous in New South - Wales. Linn. Soc., New South Wales, Proc., vol. 7, pp. - 315-316. 1882. - - [67] Guthrie, F. B., and Turner, F. Supposed Poisonous Plant. - Agric. Gaz., New South Wales, vol. 4, p. 86. 1894. - - [68] Bailey, F. M., and Gordon, P. R. Plants Reputed - Poisonous and Injurious to Stock, Brisbane, 1887, p. 25. - - [69] Guthrie, F. B., and Turner, F. Supposed Poisonous Plant. - Agric. Gaz., New South Wales, vol. 4, p. 87. 1894. - - [70] Martin, C. J. Report on the Investigation into the - Effects of Darling Pea (Swainsona Galegifolia) upon Sheep. - Agric. Gaz., New South Wales, vol. 8, p. 367. 1898. (Further - literature on the indigo disease will be found in Bailey, F. - M., and Gordon, P. R. Plants Reputed Poisonous and Injurious - to Stock, Brisbane, 1887, p. 25). - - NOTE.--In Canada a chronic disease associated with cirrhosis - of the liver results from eating ragwort, or _Senecio - jacobaea_. See Dept. of Agriculture, Canada, Rept. of - Veterinary Director General, 1905, Ottawa, 1906, p. 31.--In - South Africa a disorder known as nenta appears in goats after - eating certain plants, especially _Cotyledon ventricosa_. See - Hutcheon, D., Nenta, in Agric. Journ. Cape of Good Hope, vol. - 14, p. 862. 1899. - - - - -=PATHOLOGICAL CONDITIONS IN LOCOED ANIMALS AS DESCRIBED ON THE RANGE.= - - -The pathological features as described by previous writers are a -softening and ulceration of the stomach walls[71] and a degeneration of -the walls of the intestines with or without perforations. The peritoneum -may be found inflamed.[72] The peritoneum and omentum in one case (cow), -reported by Sayre, were covered with small nodules. These were probably -tubercular in origin. The colon in one horse was found enormously -distended, while the coecum and small intestines were normal,[73] save -that the walls appeared thin. - -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 space 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. Assoc. 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 analysis 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_, analyzed 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 principally 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, - passing 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] - -In 1888 Hill reported that a species of Astragalus was acting -detrimentally on cattle, goats, and sheep in Cyprus and that these -animals fell down as if intoxicated, and also that the natives in time -of great drought feed their cattle with this plant mixed with straw, but -that they were always made sick until they became used to it. - -In 1885 Professor Sayre, of the University of Kansas, undertook the -investigation of the loco question. His first report was made in the -Transactions of the Kansas Academy of Sciences for 1885, and his reports -have been continued at various periods up to 1904. The results of his -experiments on various animals--dogs, cats, and frogs[99]--have been -entirely negative. He administered alcoholic preparations to himself and -took them until they became too nauseous to continue, and found they -produced absolutely no symptoms besides the nausea. He suggests, -however, that if the plant really is poisonous it is due to its fine -hairs, which might mechanically cause death. Sayre has stated that he -has sent thousands of pounds of the dried loco plants to various -investigators in America and Europe, but all reports were negative as to -pharmacological activity. He has, however, done some work on the pure -chemistry of the plant and found that the plant contained 10 per cent of -moisture and yielded 12.01 per cent of ash. Of this ash, 25 per cent was -soluble in water, while 50.6 per cent was soluble in HCl. The insoluble -portion consisted largely of silica. He found CaO, K_{2}O, MgO, -Al_{2}O_{3}, and Fe_{2}O_{3}, with the acid radicals SO_{3}, Cl, -P_{2}O_{5}, CO_{2}, and SiO_{2}.[100] Although Sayre claims that the -plant is physiologically inactive, he tried by chemical means to isolate -a physiologically active body and, naturally enough under the -circumstances, failed to find one. He claims that while the plant might -give alkaloid reactions, he was unable to isolate this body in a pure -state, and that alfalfa reacted similarly. - -The investigation on animals was continued by Kennedy.[101] He -administered an infusion of 1/2 ounce of green _Astragalus mollissimus_ -to a fasting dog weighing 23 pounds, but there were no symptoms after 12 -hours. A decoction of 1 ounce of the green plant and one of 4 ounces of -the dried plant were likewise without action. Extracts with hydrochloric -acid were also inactive. When 400 grams of the dried and powdered plant -were fed in substance the result was merely to increase the appetite. -The organic acid obtained from 4 ounces of the plant was also found to -be inert. - -Kennedy did not state in what season the plant was collected and from -what locality it was obtained, but says simply that the plant extract -was inactive to a dog, a carnivorous animal, and that therefore the -plant is nonpoisonous. He adds that death might be due to the tough -fibers and indigestible character of the plant. He overlooks, however, -the fact that the plant might vary in its toxicity, and he infers from -the experiments on carnivorous animals that these results would hold -good for herbivora, yet he does not claim that carnivora become locoed -in nature. - -Kennedy found that the plant lost 80 per cent in weight on drying and -that the water extract which represented 30.6 per cent of the powdered -and dried plant contained magnesium sulphate and sodium chlorid, tannic -acid, gum, coloring matter, an extractive, and a "peculiar organic -acid." The ashed plant yielded 20 per cent of ash, consisting of -magnesium sulphate, sodium chlorid, alumina, silica, and a trace of -iron. "The abundant precipitate produced by the alkaline hydrates, -potassium, sodium, and ammonium was found to consist of magnesium -hydrate, an abundance of this base being present in the plant." Kennedy -also obtained alkaloidal reactions, but failed to isolate the body -giving these reactions. - -In 1889 the investigations were greatly stimulated by the report of -Doctor Day,[102] then of the University of Michigan. She claimed that -she was able to produce marked physiological symptoms, using both -_Astragalus mollissimus_ and _Aragallus lamberti_ in her work. She -administered daily 60 to 70 c.c. of a decoction[103] of the plants to -kittens, together with abundant milk and other food. She states that in -two days-- - - The kittens became less active, the coat grew rough, appetite for - ordinary food diminished and fondness for the "loco" increased, - diarrhea came on, and retching and vomiting occasionally occurred. - The expression became peculiar and characteristic. Emaciation and - the above symptoms progressively increased until the eighteenth - day, when periods of convulsive excitement supervened. At times the - convulsions were tetanic in character; frothing at the mouth and - throwing the head backward as in opisthotonus were marked. At other - times the kitten would stand on its hind legs and strike the air - with its forepaws, then fall backward and throw itself from side to - side. These periods of excitement were followed by perfect quiet, - the only apparent sign of life being the respiratory movements. - After a short interval of quiet the convulsive movements would - recur. These alternate periods of excitement and quiet lasted - thirty-six hours, when the posterior extremities became paralyzed, - and the kitten died about two hours afterward. There was no - apparent loss of consciousness before death. - - The post-mortem examination revealed the presence of ulcers in the - stomach and duodenum. Some of the ulcers had nearly perforated the - walls of the stomach and duodenum. The heart was in diastole; brain - and myel appeared normal. As might be expected from the emaciated - condition, the entire body was anaemic. - - In a second case 60 to 70 cubic centimeters of a more concentrated - decoction were fed daily, with other food as before, to a vigorous - adult cat. The symptoms of inactivity, loss of appetite, rough - coat, diarrhea, and the peculiar expression of countenance were as - in the first case. By the twelfth day the cat was wasted almost to - a skeleton, and was correspondingly weak. Paralysis of the hind - limbs came on, and the cat died on the thirteenth day. There were - no periods of excitement in this case. - -These cats developed a craving for the decoction and "would beg for it -as an ordinary kitten does for milk, and when supplied would lie down -contented." - -Doctor Day made controls with healthy animals under the same conditions, -with the exception that they received no loco plant. She also fed a -young wild jack rabbit on milk and grass for a few days and then -substituted fresh loco plants for grass. - - At first the "loco" was refused, but after two or three days the - "loco" was eaten with as much relish as the grass had been. After - ten days of the milk and "loco" diet the rabbit was found dead, - with the head thrown back and the stomach ruptured. - - Subcutaneous injections of the concentrated decoction caused - nervous twitchings in frogs and kittens, and if large amounts were - used death followed in from one to two hours from paralysis of the - heart. The same symptoms were produced in frogs by the injection of - an alcoholic extract of the residue left after the evaporation to - dryness of the decoction. - -In other words, Doctor Day was able to produce a chronic form of loco -poisoning with the characteristic symptoms so often described save in -the occurrence of diarrhea. Diarrhea is not usually noted on the range. -Sayre had already reported an ulcerated condition of the intestines of a -locoed cow similar to that described by Doctor Day as occurring in cats. -Doctor Day urged that the reason previous experimenters failed to -produce symptoms was that they had used too small an amount of the plant -and that by systematic feeding to healthy cats cases of loco disease may -be produced. - -Storke states that "Dr. V. C. Vaughan, of the University of Michigan, -has since fully corroborated Dr. Day's views."[104] - -In her experiments Doctor Day used the leaves, roots, and stems of the -plants gathered in September. She believed that the greatest amount of -poison is present in autumn and winter. She later undertook the -isolation of the active principle, and proceeded as follows:[105] - - The roots, stems, and leaves were boiled ten hours, strained, and - the decoction concentrated to a sirup, poured, while hot, into a - hot flask, corked and set away. At the end of ten days the sirup - had separated into two layers--the upper a blackish liquid, the - lower a brownish sediment. The liquid was poured into a flask and - covered with six times its volume of very dilute alcohol, 30 per - cent (the sediment also was washed with dilute alcohol, to insure a - complete removal of the liquid), corked, and let stand three days; - agitated occasionally, then filtered, and the filtrate slowly - evaporated in the air, when crystals were formed. It was found - important not to hurry the evaporation, for when this took place - too rapidly the crystals did not form. - - These crystals are microscopic in size, blue-white in color, and of - a variety of forms. The most characteristic are slender and - pointed, arranged in rosettes or grouped in various ways. They are - soluble in distilled water and very dilute alcohol, very sparingly - soluble in strong alcohol, not soluble in chloroform or ether. - - The evaporated mass containing the crystals, when dissolved in - distilled water, is slightly acid in reaction. A small amount of - this fed to a kitten produced the train of characteristic toxic - symptoms--sleepiness, loss of appetite, retching, and - diarrhea--that is produced by quite large amounts of the decoction. - -The crystals Sayre[106] claims to have already seen. He says that they -gave no precipitate with Mayer's reagent, platinum chlorid, or with -ammonia, but that barium chlorid and ammonium oxalate gave a -precipitate, and he believes that they were in reality an inorganic -combination of calcium, so that while Doctor Day may have obtained an -extract which produced characteristic symptoms she certainly has not -isolated any pure active principle. Later she admitted that it was not -possible "to make positive statements as to the chemical character of -the active principle."[107] - -In 1884 there was a fatal outbreak of a disorder in horses in portions -of the Missouri Valley in Iowa, Nebraska, and Dakota. This was almost -uniformly fatal in a few weeks or months. The animals lost strength and -became emaciated, although they were kept in pasture where there was -abundant grass. There was marked stupor, the animals falling asleep -while eating, and they "would remain standing for a whole week, sleeping -much of the time, with the head resting upon some object." The -post-mortem examination showed that "in every instance there was marked -hemorrhagic effusion into the fourth ventricle, the liver and spleen -were abnormally dense, the walls of the intestines were almost destitute -of blood, and the stomach enormously distended with undigested food." -The post-mortem find and clinical symptoms suggested to Stalker[108] -that this disorder was due to some plant analogous to _Astragalus -mollissimus_. He found abundant in these regions _Crotalaria -sagittalis_, or rattle-box, one of the so-called loco weeds, and by the -administration per os to a young horse of an infusion of 15 pounds of -the plant, given in two days, produced the clinical symptoms and the -post-mortem condition of the brain which he previously observed on the -range. - -Power and Cambier[109] undertook the chemical study and the isolation of -the active principle of this plant, together with that of _Astragalus -mollissimus_. They found that the _Astragalus mollissimus_ if distilled -with water yielded a distillate which possessed a peculiar odor, which -they thought due to a trace of volatile oil. On distilling with alkali -they obtained ammonia and a trace of trimethylamine. In the case of -Crotalaria only ammonia was found.[110] They argued that because -trimethylamine was not obtained in this case choline was not present. On -distilling the _Astragalus mollissimus_ with acidulated water -(H_{2}SO_{4}) the distillate was found to contain acetic acid--settling -the nature of the "peculiar organic acid" described by Kennedy. From -this plant they obtained a resin or mixture of resinous bodies by -extracting the plant with alcohol, and after concentration precipitating -with acid water. These resins in doses of from 2 to 5 grains failed to -produce any symptoms in kittens. - -An albuminoid which was obtained by precipitating a concentrated aqueous -extract of _Astragalus mollissimus_ by means of alcohol likewise was -found to be inactive to a kitten in doses corresponding to 50 grams of -the crude plant. A globulin which was isolated by precipitation from a -10 per cent sodium chlorid solution proved also to be inactive in doses -of 0.2 gram. They then extracted 3 kilograms of these plants with 1/2 -per cent sulphuric acid, and after evaporation to a thick gum the mass -was extracted with strong alcohol, the alcoholic solution was -evaporated, and the alcoholic residue taken up in water and precipitated -by neutral and basic lead acetates, and after removing the lead with -sulphureted hydrogen the filtrate gave precipitates with various -alkaloidal reagents. The sirupy residue which they obtained from -_Astragalus mollissimus_ by decomposing the precipitate with Mayer's -solution administered to kittens in doses of 0.1 gram produced merely -frothing at the mouth with profuse flow of saliva, but the animals soon -recovered. The presence of a large amount of calcium was shown but not -estimated quantitatively. - -Power and Cambier summed up their conclusions by stating that both the -Astragalus and the Crotalaria contain very small amounts of toxic -alkaloids, to which they believe the symptoms of poisoning produced were -due. Their work from a chemical standpoint is excellent, but from a -pharmacological point of view seems to be deficient; in fact, Power does -not claim to be a pharmacologist. What would seem to be the proper -course would have been to test for themselves the action of the plant -on various animals and, after deciding which reacted most -characteristically, test, after various precipitations, both the -precipitates and filtrates on various animals to see whether the -original symptoms and pathological lesions could be produced. They -failed, however, to test their mother substance. It is well recognized -that plants grown under varying conditions and on different soils vary -in the amount of the physiologically active principle they contain. - -In the case of Crotalaria, Power and Cambier had before them the -experiment of Stalker, in which he reproduced the disorder by feeding -the plant extract to horses, yet they claimed that the body which they -administered was the active principle, merely because it produced some -frothing at the mouth and salivation in a kitten. The percentage of -active principle they found would be too small to account for the -symptoms, except in the case of a very active compound. - -Certain of these precipitates were also later examined physiologically -by O'Brine.[111] He also found the resin precipitated from an alcoholic -extract of the plant and also the alcoholic extract from 2.2 pounds of -the dried _Astragalus mollissimus_ to be physiologically inactive. - -Oatman,[112] using Power and Cambier's method with alfalfa (_Medicago -sativa_), obtained a noncrystalline mass which when given in 0.1 gram -dose caused frothing at the mouth in a kitten, but no serious symptoms. -This 0.1 gram represented about 5 pounds of powdered leaves and tops of -the plants. - -Since the appearance of Power and Cambier's work Sayre has published -various papers on the loco weeds in the Transactions of the Kansas -Academy of Sciences for 1903-4, vol. 19, p. 194, 1905; 1901-2, vol. 18, -p. 141; Seventh Biennial Report of the State Board of Agriculture of -Kansas, vol. 12, p. 97, 1891; Journal of the Kansas Medical Society, -vol. 4, pp. 222 and 241, 1904, etc. He has contributed nothing -especially new, but says that "the old theory that an alkaloidal poison -is secreted in the plant causing the loco trouble has not been found -tenable," but wishes to be understood that he does not discredit the -ground for the opinion that in some mysterious way certain disorders -occur in cattle in connection with what is commonly called loco-weed. He -suggests that this connection might be somewhat similar to the -relationship between the disorder caused by over-feeding half-starved -animals on clover or alfalfa[113] and has had the plant analyzed as to -its nutritive value, giving the table in the Transactions of the Kansas -Academy of Sciences, vol. 19, p. 194. He makes the suggestion that any -injurious action the plants may have might be due to the fine, hair-like -projections on the plant which mechanically set up irritation. This -supposition can be thrown out at once by the experiment of Day and -others, who induced symptoms in animals by extracts of the plant, and by -the fact that other coarse plants do not act similarly. This fine, -hair-like material was found to constitute about 33 per cent of the -plant on grinding. But Sayre himself does not seem to be positive as to -any conclusion. He, like O'Brine and others, has obtained alkaloidal -reactions from the plant, but states he has obtained similar ones from -alfalfa.[114] At one time he said: - - I do not consider loco directly or indirectly the cause of the - condition, but am of the opinion that what is called "locoed" is, - first, congestion of the brain and spinal marrow (causing blindness - and first symptoms), and, second, softening to a greater or less - extent.[115] These terms describing the alleged symptoms of - "locoism" might occur in well recognized diseases resulting from - brain lesions, which latter occur in so-called forage poisoning and - poisoning from foul drinking water, etc. - - We are not prepared to affirm or deny that the loco-weed produces a - train of symptoms characteristic of the plant.[116] - -Again Sayre states: - - It seems not unreasonable to suppose that the peculiar condition of - the animals of the plains, when they gorge themselves with this - highly nitrogenous weed, has something to do with the disease. A - condition of malnutrition may set in and give rise to the rapid - growth of a toxic-producing micro-organism or an irritating - principle. This principle may be capable of cultivation and of - producing disease artificially. Be this as it may, we feel - warranted in saying that the so-called poison is a development - within the animal, not a product preexisting in the weed itself. - -Sayre also suggests the possibility of the plants producing hydro-cyanic -acid, which, it is well known, occurs in sorghum.[117] In the Journal of -the Kansas Medical Society (vol. 4, p. 243), he claims to have isolated -a crystalline body, but this he has not tested physiologically. Sayre -especially deserves credit for keeping the loco investigation alive, and -no doubt his change in position is due to his lack of facilities for -pharmacological testing. - -Carl Ruedi[11] fed rabbits daily by a stomach tube with 10 c.c. of an -extract (unstated strength) of _Astragalus mollissimus_ and recorded the -following results: - - After only five injections one of the rabbits died, and the - post-mortem showed to a nicety the congestion of the whole tract of - the vena portae and the anaemia of the brain. I put six rabbits under - the influence of loco, and the effect was marked, but not rapid, if - not given in very concentrated solutions. The solutions were - prepared differently, and each of the rabbits had its own - preparation, but the effect was nearly the same. In the beginning - loco acts as a stimulant; the animals get lively, hilarious, - running about; cleaning themselves, etc. This lasts about eight - hours, then they become very quiet, sit in a corner of a box, and - one can do with them pretty nearly what one likes; they do not move - from the place, or just run into another corner, to fall back into - the same complacent reverie. One can leave the door open and hammer - away at the box, but they do not show any inclination to run away. - During the excitement, however, they become fierce, and I had once - the opportunity to watch one of the drollest things possible: One - of the rabbits, two hours after dosing it, got loose and ran under - a porch. A heavy tomcat came near this hole, and commenced sniffing - about; this offended the rabbit highly, and it jumped on the neck - of the cat, bit it through the skin, and the cat ran screaming - away. When the animals are first under the influence of moderate - doses of loco, they suffer greatly from hyperaesthesia of the - cutaneous nerves; when one touches them with a stick while lying in - a corner, without hurting them, one sees the platysma working away - very forcibly, and sometimes they utter sounds of pain. According - to my experiments the loco-weed works slowly but surely; as soon as - the anaemia of the brain sets in, the animals act in every respect - mad like; one hour they are excitable, and then again dull and - languid as can be. The rabbits eat, when well, very quickly, and - whenever they have opportunity; not so the locoed rabbit; he eats - slowly for a minute or two, then he goes into a corner and - meditates, comes forward to nibble at a carrot or a piece of - cabbage, but he never eats greedily, and does not steal it from the - mouth of his neighbor, or only very exceptionally. I observed these - rabbits for ten days; they did not die, because I gave them weaker - solutions; but they all became very ill, and as I had to leave the - park I killed them with the needle inserted into the medulla - oblongata, and made the post-mortem. In all of these cases I found - great congestion in the abdomen, and marked anaemia of the brain. - The congestion of the vena portae commences certainly very early, - but still the first symptoms are the nervous symptoms, first as - excitants, then depressing or sedative, with a marked hyperaesthesia - of the cutaneous nerves. - -Ruedi made an attempt to isolate the active principle and separated a -base, which he calls "locoin," from an ether shaking. This base, -however, he found to be physiologically inactive, but believes the -activity to be due to a body which he calls "loco-acid," which is -present in the mother liquid after the shaking with ether. He, however, -has not obtained this in any degree of purity and gives no chemical data -to substantiate this statement save that the fluid was acid. - -Experiments made at the University of Pennsylvania with certain loco -plants on cats, dogs, and rabbits proved negative.[119] - -Other experiments on rabbits have been made by Doctor Lewis. These -rabbits were fed on the leaves, stem, and whole plant, and also extracts -of one of the loco plants (presumably _Astragalus mollissimus_) for one -or two months, without producing any noticeable effect.[120] - -This uncertainty in the results of the investigation as to the cause of -the loco disease turned the attention of observers into other lines. -President Ingersoll,[121] of the State Agricultural College of Colorado, -in his autopsies on sheep was struck by the presence of tapeworms -(_Taenia expansa_) in the gall duct and small intestines. He apparently -tried to prove a relationship between the tapeworms and the locoed -condition by feeding the extract of a loco plant to sheep, and thus -showing its harmlessness. He prepared a decoction from 20 pounds of loco -plant (the species was not stated) and boiled this down from 12 gallons -to 1 quart. This concentrated extract was fed in three days to a -bottle-fed lamb; this lamb showed no symptoms, although kept under -observation for two weeks. This theory of the causation of loco by worms -was also considered by Curtice,[122] and later brought forward by -Steele[123] and Marshall.[124] This idea is very suggestive when -considered in relation to the etiology of bothriocephalous anaemia.[125] - -Others, again, have claimed that the disease is due to a parasite found -upon the loco plants, but all specimens examined by entomologists proved -to be harmless.[126] - -Lloyd, from his study of the subject, says: - - From first to last I have failed in obtaining a characteristic - proximate principle, either from the fresh or dried plant. The - disease called loco was as murky as the milk sickness so prevalent - in the new settlements of Indiana and Kentucky in early days, and, - like the numberless herbs that have been presumed to produce that - obscure peculiar disease, milk sickness, loco was unresponsive to - my chemistry.[127] - - It may be safely said that if a specimen of the plant were to be - examined in the ordinary manner by a chemist who had no idea of its - importance he would report that it did not contain a characteristic - proximate constituent.[128] - - Can it be that an admixture of loco and some undetermined plant or - earth infected with bacteria taken with the roots, each innocuous - under other conditions, can by digestion together in the stomach - and intestines result in the production of a poison?[129] - - To sum up, it seems to the writer that the poison of loco is a - product, and not an educt.[130] - -But Lloyd adds, in speaking of the reports of various experts and -ranchmen: - - Their description concerning its toxic action on animals agreed, - and it was folly to argue that so many observers from so many - sections of the country could be misled. There must be an - undetermined something behind the loco-weed.[131] - -In 1893 O'Brine, from Colorado, and Mayo, from Kansas, reported on their -work with the loco plants. O'Brine failed to isolate any alkaloidal or -other poisonous body, and his feeding experiments on himself and on -rabbits having failed, he sums up in despair: "The more I examine the -loco question, the more I am persuaded that we must look for some other -cause besides the loco-weed."[132] At the end of his report he gives -some ash analyses but fails to interpret them. He also fails to give -details as to the method of obtaining and estimating his ash. O'Brine's -ash analyses are as follows: - - KEY TO ASH ANALYSIS: - A = SiO_{2}. - B = Fe_{2}O_{3} and Al_{2}O_{3}. - C = CaO. - D = MgO. - E = K_{2}O. - F = Na_{2}O. - G = H_{2}SO_{4} - H = Cl. - I = P_{2}O_{5}. - J = CO_{2} - - ------+-----+-----+-----+-----+----+-----+----+----+----+----+-----+ - Plant.|Total| | | | | | | | | | | - |ash. | A | B | C | D | E | F | G | H | I | J | - ------+-----+-----+-----+-----+----+-----+----+----+----+----+-----+ - AM |12.15|32.77|16.26| 6.05|3.11|13.30|3.21|3.9 |0.47|6.12|10.55| - | | | | | | | | | | | | - AL |13.52|17.08|12.21|14.27|2.62|17.26|5.75|3.22|3.87|3.30|17.37| - | | | | | | | | | | | | - AC |12.36| 7.82| 5.97|12.10|3.55|23.35|3.38|5.56|9.0 |4.67|20.62| - | | | | | | | | | | | | - ------+-----+-----+-----+-----+----+-----+----+----+----+----+-----+ - KEY TO PLANTS: - AM = _Astragalus mollissimus_ (whole plant) - AL = _Aragallus lamberti_ (whole plant) - AS = _Astragalus caryocarpus_ - -These analyses are evidently incorrect, as O'Brine estimates a carbon -content of 4.13 per cent for the first, and for the second 2.22 per -cent, showing incomplete combustion. - -Mayo[133] experimented with alcoholic and aqueous extracts of dried -_Astragalus mollissimus_ on guinea pigs, with negative results, and was -first led to deny a relationship between the disease and the plants. -Later, as a result of the post-mortem findings, he was convinced that -his first conclusion was wrong and that "the disease is certainly the -result of animals feeding upon the loco-weed." Mayo says: - - A careful survey of the experiments performed and observations - noted leads me to the opinion that the disease known as "loco" is - the result of malnutrition, or a gradual starvation, caused by the - animals eating the plants known as "loco weeds," either _Astragalus - mollissimus_ or _Aragallus lamberti_. If there is a narcotic - principle in the plant, chemists have failed to find it and a fluid - extract does not possess it, and a ton of the plant eaten by an - animal ought to contain enough of the poisonous properties to - destroy an animal. - -Kobert[134] has also tested the activity of _Astragalus mollissimus_ and -says, "Ich fand _Astragalus mollissimus_ ziemlich unwirksam." - -Doctor McEackran[135] fed dried _Astragalus mollissimus_ and _Aragallus -lamberti_ mixed with feed to a stabled animal for two months without -result. (Animal not stated).[136] Similar negative experiments are -reported from the State of Washington, but the amounts used were too -small to form any conclusions.[137] - -Mr. V. K. Chesnut[138] has busied himself with the loco problem, but -mainly in an executive capacity, his own efforts being directed to the -study of the relation of the loco plants to the disease on the range. He -has done no laboratory work. Chesnut and Wilcox made numerous autopsies -on sheep and experiments on animals. They claimed that an extract of -_Aragallus spicatus_ produced some slight narcotic action in rabbits. -Their pathological examinations failed to show any characteristic -lesion, but they state that the cerebral membranes were in all cases -slightly congested. They deny any causative relationship to the presence -of worms or with feeding upon alkalis. They believe that sheep are more -likely to become locoed if not salted regularly. Chesnut describes one -case in which a lamb became locoed by nursing from a locoed mother. - -In 1901 Reid Hunt, at that time a special agent of the United States -Department of Agriculture, studied the loco question in Montana, working -mainly with _Aragallus spicatus_. He moistened the ground-up plant with -93 per cent ethyl alcohol and then percolated it until exhausted. This -extract was evaporated and taken up with water so that 1 c.c. of the -solution corresponded to 10 grams of the plant. This was fed to an -active young rabbit weighing 490 grams, 6 c.c. being fed by the mouth -and followed in about an hour by 10 c.c. more, and two hours after this -by 15 c.c. This rabbit showed no symptoms during the following day. The -next day it was very dull and there was marked muscular weakness, as the -rabbit's legs were spread wide apart and his nose rested on the ground. -Later respiration became very slow and the pupils were dilated. The -paralytic symptoms increased and finally, after a convulsive movement, -the animal died, thirty-six hours after the first feeding. Hunt merely -states of the post-mortem examination that the stomach was well filled -and that the "walls seem normal." - -Hunt tried to isolate an active principle by the Dragendorff method, but -failed to obtain any physiologically active shakings. He tried -hypodermic injections of 80 per cent alcohol extractions of the fresh -green plant, and after the injection of an extract corresponding to 60 -grams of the fresh plant there was no effect produced. He tried to -induce symptoms by feeding the plant itself to rabbits, but was -unsuccessful, as the rabbits refused to eat the plant. He was not able -to induce symptoms with the extracts of the dried plant.[139] - -Marshall[140] studied the loco question with regard to sheep and -practically denies the existence of a locoed condition due to eating the -loco plants, but believes the condition due to bad feeding, parasitism, -etc. He lays great stress upon the presence of worms, but fails to see -that they may be merely a secondary infection superimposed upon an -already morbid condition produced by eating the plants. Others have -claimed that the cause is an insect living upon the loco plants. Others, -again, have suggested an analogy with trypanosome disorders. - -Chesnut has held the view that many of the cases of so-called locoed -sheep were really due to parasites, but that there was a true locoed -condition due to eating the loco weeds. - -The lack of agreement in the results of the investigators has caused -many to doubt any positive relation between the plant and the disease, -and even as late as 1904 Payne[141] practically says these diseases are -due to lack of nutrition and not to the loco plant. The matter has been -summed up in a recent work as follows: - - Though many chemists have sought for the constituents, none have - been able to locate the active properties, the trace of alkaloids, - resins, volatile and fixed oils having each in turn been found - destitute of it. Yet the poisonous properties are fully established - by field observations. The destructiveness of these plants to stock - is so great as to have probably caused upward of a million dollars - loss in the aggregate, and large bounties have been offered by - State governments for an effective method of avoiding such losses. - It is considered very probable that the poisonous constituent is - albuminoidal.[142] - - * * * * * - -FOOTNOTES: - - [83] Storke, B. F. The Loco Weed. Med. Current, vol. 8, p. - 155. 1892.--Kellogg, A. California and Colorado "Loco" - Poisons. Cal. Acad. Sci. Proc. for 1875, vol. 6, p. 3. 1876. - - NOTE.--The very early reports of these loco plants were - purely botanical. See Torrey, J., Botany, in Report on the - United States and Mexican Boundary Survey, by W. H. Emory, - vol. 2, p. 56, 1859; also Botanical Register, London, vol. - 13, pl. 1054, 1827. - - [84] Vasey, G. Plants Poisonous to Cattle in California. - Rept. of Commissioner of Agriculture for 1874, p. 159. 1875. - - [85] Vasey, G. Botanical Notes. Monthly Reports of Dept. - Agriculture for 1873, p. 503. 1874. - - [86] Vasey, G. Botanical Notes. Monthly Reports of Dept. - Agriculture for 1874, p. 513. 1875. - - [87] Brewer, W. H., and Watson, S. Geological Survey of - California, Botany, vol. 1, p. 155. 1876. - - [88] Rothrock, J. T. Notes on Economic Botany, in G. M. - Wheeler's Report upon U. S. Geographical Surveys West of the - One Hundredth Meridian, vol. 6, p. 43. 1878. - - [89] Kellogg, A. California and Colorado Loco Poisons. Cal. - Academy of Sciences, Proc., 1875, vol. 6, p. 3. 1876. - - [90] Rothrock, J. T. Poisonous Properties of the Leguminosae. - Acad. of Nat. Sci., Phila., Proc., vol. 29, p. 274. 1877. - - [91] Prescott, A. B. Laboratory Notes--A Partial Analysis of - the Oxytropis Lamberti. Amer. Journ. Pharm., vol. 50, p. 564. - 1878. - - [92] Rept. of Commissioner of Agriculture for 1878, p. 134. - 1879. - - [93] Rept. of Commissioner of Agriculture for 1879, pp. 89, - 90. 1880. - - [94] Rept. of Commissioner of Agriculture for 1886, p. 75. - 1887. Rept. of Commissioner of Agriculture for 1884, p. 123. - 1884. - - [95] Rothrock, J. T. Notes on Economic Botany, in G. M. - Wheeler's Report upon U. S. Geographical Surveys West of the - One Hundredth Meridian, vol. 6, p. 43. 1878. - - [96] Gibbons, H. Poisonous Effects of Crotalaria--Vulgo - Rattle Weed, Loco Weed. Pacific Med. and Surg. Journ., vol. - 21, p. 496. 1878-79. - - [97] Ott, I. Physiological Action of Astragalus Mollissimus. - New Remedies, vol. 11, p. 227. 1882. - - [98] Hill, J. R. Note on a Species of Astragalus from Cyprus. - Pharm. Journ. and Trans., 3 s., vol. 18, p. 712. 1887-88. - - [99] Sayre, L. E. Loco-Weed. Proc. Amer. Pharm. Assoc., vol. - 36, p. 112. 1888. - - [100] Sayre, L. E. Loco Weed. Amer. Vet. Rev., vol. 11, p. - 556. 1887. - - [101] Kennedy, J. Loco Weed (Crazy Weed). Pharm. Rec., vol. - 8, p. 197. 1888. - - [102] Day, M. G. Experimental Demonstrations of the Toxicity - of the "Loco Weed." N. Y. Med. Journ., vol. 49, p. 237. 1889. - - [103] Presumably a 10 per cent decoction, U. S. P. - - [104] Storke, R. F. The Loco Weed. Med. Current, vol. 8, p. - 157. 1892. - - [105] Day, M. G. The Separation of the Poison of the "Loco - Weed." N. Y. Med. Journ., vol. 50, p. 604. 1889. - - [106] Sayre, L. E. Active Principle of Loco Weed. Notes on - New Remedies, vol. 2, No. 12, p. 1. - - [107] Day, M. G. Loco Weed, in F. P. Foster's Reference-Book - of Practical Therapeutics, vol. 1, p. 588. 1896. - - [108] Stalker, M. 1st Ann. Rept. State Vet. Surg. Iowa, p. - 16. 1885. - - [109] Power, F. B., and Cambier, J. Chemical Examination of - Some Loco-Weeds. Pharm. Rundschau, vol. 9, p. 8. - 1891.--Power, F. B. Notes on the So-called Loco Weeds. Pharm. - Rundschau, vol. 7, p. 134, 1889.--See also Hoffmann, F., - Loco-Weeds, in Pharm. Rundschau, vol. 7, p. 168. 1889. - - [110] Kennedy, J. Pharm. Rec., vol. 8, p. 197. 1888. Kennedy - also obtained ammonia from _Astragalus mollissimus_. - - [111] O'Brine, D. Progress Bulletin on the Loco and Larkspur. - Colo. State Agric. Coll. Bul. 25, p. 18. 1893. - - [112] Oatman, H. C. The Poisonous Principle of Loco Weed. - Notes on New Remedies, vol. 4, p. 14. 1891-92. - - [113] Sayre, L. E. Loco Weed. Kans. Acad. Sci. Trans., vol. - 18, p. 141. 1903. - - [114] Sayre, L. E. Loco Weeds. 7th Bienn. Rept. Kans. State - Board Agric. for 1889-90, vol. 12, pt. 2, p. 99. 1891. - - [115] Sayre, L. E. Further Report on Loco Weeds. Notes on New - Remedies, vol. 4, p. 80. 1891-92. - - [116] Sayre, L. E. The Loco Disease. Journ. Kans. Med. Soc., - vol. 4, pp. 241-243. 1904.--What is Insanity in Lower - Animals? Journ. Kans. Med. Soc., vol. 4, p. 222. 1904. - - [117] Sayre, L. E. Loco Weed. Kans. Acad. Sci. Trans., vol. - 18, p. 144. 1903. - - [118] Ruedi, C. Loco Weed (Astragalus Mollissimus): A - Toxico-Chemical Study. Trans. Colo. State Med. Soc., p. 418. - 1895.--Also Treatment of Animals Poisoned by Loco Weed - (unpublished article). - - [119] The "Loco Disease." Therap. Gaz., vol. 12, p. 30. 1888. - - [120] Sayre, L. E. Loco Weed. Kans. Acad. Sci. Trans., vol. - 18, p. 142. 1903. - - [121] Sayre, L. E. Loco Weeds. 7th Bien. Rept. Kansas State - Board Agric. for 1889-1890, pt. 2, p. 98. 1891. - - [122] Curtice, C. Tape-Worm Disease of Sheep of the Western - Plains. Bur. Animal Industry, 4th and 5th Ann. Rept., p. 167. - 1889. - - [123] Steele, C. D. New Theory about Loco. Farm and Ranch, - vol. 20, No. 35, p. 1. 1901. - - [124] Marshall, H. T. Loco Weed Disease of Sheep. Johns - Hopkins Hospital Bul., vol. 15, p. 181. 1904.--Data as to - these parasites of sheep may be found in Curtice, C., The - Animal Parasites of Sheep, Bur. Animal Industry, Rept., 1890. - - [125] Faust, E. S., and Tallquist, T. W. Ueber d. Ursachen - der Bothriocephalus-anaemie. Arch. f. Exp. Path., vol. 57, p. - 367. 1907. - - [126] Walshia Amorphella and the Loco Weed. Insect Life, vol. - 2, p. 50. 1889-90. Snow, F. H. Loco-Weed. Science, vol. 9, p. - 92. 1887. - - [127] Lloyd, J. U. Loco, or Crazy Weed. Eclectic Med. Journ., - vol. 53, p. 482. 1893. - - [128] Lloyd, J. U., l. c., p. 483. - - [129] Lloyd, J. U., l. c., p. 484. - - NOTE.--Eccles had previously announced a somewhat similar - idea. Sayre, L. E. Loco Weed. Proc. Amer. Pharm. Assoc., vol. - 36, p. 115. 1889. - - [130] Lloyd, J. U., l. c., p. 486. - - [131] Lloyd, J. U., l. c., p. 483. - - [132] O'Brine, D. Progress Bulletin on the Loco and Larkspur. - Colo. State Agric. Coll. Bul. 25, p. 17. 1893. - - [133] Mayo, N. S. Some Observations on Loco. Kans. State - Agric. Coll. Bul. 35, p. 116. 1893. - - [134] Kobert, R. Lehrb. d. Intoxikationen, p. 615. 1893. - - [135] O'Brine, D. Progress Bulletin on Loco and Larkspur. - Colo. State Agric. Coll. Bul. 25, p. 13. 1893. - - [136] After the manuscript of this bulletin was sent to the - printer it was learned through Professor Carpenter that the - animal was a horse. - - [137] Nelson, S. B. Feeding Wild Plants to Sheep. Bur. Animal - Industry, Bul. 22, p. 12. 1898. - - [138] Chesnut, V. K., and Wilcox, E. V. Stock-Poisoning - Plants of Montana. U. S. Dept. Agric., Div. Bot., Bul. 26, p. - 95. 1901.--Wilcox, E. V. Plant Poisoning of Stock in Montana. - Bur. Animal Industry, 17th Ann. Rept., p. 111. 1900. - - NOTE.--The writer wishes to acknowledge the great literary - help Mr. Chesnut's card catalogue has been to him in the - preparation of this paper. - - [139] Unpublished report. - - [140] Marshall, H. T. Loco Weed Disease of Sheep. Johns - Hopkins Hospital Bul., vol. 15, p. 182. 1904. - - [141] Payne, J. E. Cattle Raising on the Plains. Colo. Agric. - Expt. Sta. Bul. 87, p. 16. 1904. - - [142] National Standard Dispensatory, p. 868. 1905. - - NOTE.--The field experiments of Harding and Tudor are rather - conclusive as to the relation of these plants to this - disorder. Sayre, L. E., Loco Weed, Amer. Vet. Rev., vol. 11, - pp. 553-554, 1887--Blankinship, J. W., Loco and Some Other - Poisonous Plants in Montana, Mont. Agric. Exper. Sta. Bul. - 45, pp. 83-84, 1903--Loco Disease, Therap. Gaz., vol. 12, p. - 30. 1898. - - - - -=NOTES ON VARIOUS MEMBERS OF THE LOCO-WEED FAMILY.= - - -_Astragalus caryocarpus_ is at times eaten in some of the Western -States, but is claimed by some at certain stages of its growth to -contain a poisonous principle. Frankforter,[143] from experiments on -himself, however, denies this. - -_Astragalus glycophyllus_ has been used as a diuretic and _Astragalus -exscapus_ in the treatment of syphilis.[144] "The seed of _A. boeticus_, -planted in Germany and England, are found to be the very best substitute -for coffee yet tried, and so used--roasted, parched, and mixed with -coffee."[145] _Astragalus nuttallianus_, according to Smith,[146] is a -highly nutritious forage plant in spring. _Astragalus crassicarpus_ has -been prophesied by him to be a valuable addition to early spring soiling -crops. _Astragalus adsurgens_ (_nitidus_) and one or two other species -of Astragalus are still used in Chinese medicine.[147] The Indians of -the Southwest are familiar with certain loco plants.[148] The Tewans of -Hano are said to eat the root of _Aragallus lamberti_, and _Astragalus -mollissimus_ is applied locally for headaches by some of the Arizona -Indians. One of these species is used as a flavoring material by the -Coahuillas and is mixed with other plants as spices.[149] _Astragalus -kentrophyta_ had a reputation among the Navajos for the treatment of -rabies.[150] The use of certain loco plants--_Astragalus -mollissimus_--has been advocated on theoretical grounds in the treatment -of certain forms of insanity, but without favorable results.[151] In -Peru and Chile _Astragalus garbancillo_, _A. unifultus_, and _A. -ochroleucus_ have been considered injurious to animals.[152] _Astragalus -glyciphyllus_ and _A. alpinus_ have been used in Europe as food for -stock.[153] - -Details as to the use of other Astragali can be found in Planchon, G., -Sur les Astragales, in Journal de Pharmacie et de Chimie, 5th series, -vol 24, p. 473, 1891; 5th series, vol. 25, pp. 169, 233, 1892. - - * * * * * - -FOOTNOTES: - - [143] Frankforter, G. B. A Chemical Study of Astragalus - Caryocarpus. Amer. Journ. Pharm., vol. 72, p. 320. 1900. - - [144] Maisch, J. M. Poisonous Species of Astragalus. Amer. - Journ. Pharm., vol. 51, p. 240. 1879.--Fleurot. Chimiques et - Pharmaceutiques sur la Racines d'Astragale sans Tiges. Journ. - de Chim. Med., vol. 10, p. 656. 1834. - - [145] Porcher, F. P. Resources of the Southern Fields and - Forests, p. 204. 1869. - - [146] Smith, J. G. Fodder and Forage Plants. U. S. Dept. - Agric., Div. Agrost., Bul. 2 (rev. ed.), p. 12. 1900. - - [147] Holmes, E. M. Notes on Chinese Drugs. Pharm. Journ. and - Trans., vol. 21, 3 s., p. 1149. 1891. - - [148] Hough, W. Environmental Interrelations in Arizona. - Amer. Anthropologist, vol. 11, pp. 143, 147. 1898. - - [149] Barrows, D. P. Ethno-Botany of the Coahuilla Indians of - Southern California, p. 67. 1900. - - [150] Matthews, W. Navajo Names for Plants. Amer. Nat., vol. - 20, p. 772. 1886. - - [151] Givens, A. J. Loco or Crazy Weed. Med. Century, vol. 1. - p. 21. 1893.--Compare Hurd, H. M. Amer. Journ. Insanity, vol. - 42, p. 178. 1885-86. - - [152] Rosenthal, D. A. Synopsis Plantarum Diaphoricarum, - Erlangen, 1861, p. 1004. Greshoff, M. Beschrijving d. Giftige - en Bedwelmeude Planten bij de Vischvangst in Gebrulk, p. 51. - 1900. - - [153] Pott, E. Handb. d. tierisch. Ernaehrung, vol. 2, p. 113. - 1907. - - - - -=LABORATORY EXPERIMENTS--PHYSIOLOGICAL.= - - -The first point in our investigations was to determine whether the plant -exerted any poisonous action and to find some animal which responded -regularly to it; then to ascertain if the lack of results of previous -investigators was not due to insufficient doses, and later to see if by -feeding smaller amounts at repeated intervals symptoms comparable to -those described as occurring on the range could not be produced. The -animal finally selected was the rabbit. - - - - -=EXPERIMENTS ON RABBITS.= - - -=ACUTE CASES.= - -_Experiment No. 1._--On September 8, 1905, an aqueous extract of 333 -grams of fresh _Astragalus mollissimus_, made in Hugo, Colo., and -shipped preserved in chloroform,[154] killed a rabbit weighing 1,616 -grams in one hour and thirty-five minutes, while an extract -corresponding to 167 grams merely caused drowsiness and loss of appetite -in a rabbit weighing 765 grams. - -_Experiment No. 2._--On November 29, 1905, a rabbit weighing 1,162.3 -grams was fed with a concentrated aqueous extract of 500 grams of fresh -_Astragalus mollissimus_, which had been shipped from Hugo, Colo., -preserved in chloroform in sealed vessels. This animal died in one hour -and ten minutes. The symptoms consisted in dullness, rapid respiration, -and signs of pain. At autopsy the stomach and upper part of the small -intestines showed hemorrhagic ecchymoses, with dilation of the dural -vessels of the brain and cord, with a clot over a portion of the spinal -cord. - -_Experiment No. 3._--On February 13, 1906, a rabbit weighing 992 grams -was fed with a concentrated aqueous extract of 500 grams of the fresh -_Astragalus mollissimus_, collected in September and preserved in -chloroform water. Before feeding, the rabbit's ears were warm and the -rabbit struggled when any attempt was made to turn him on his back. The -temperature at 10.50 a.m., the time of feeding, was 103.5 deg.F.; at 11.15 -a.m., 102.5 deg.F. At 11.30 a.m. the rabbit was breathing very rapidly -and would stay on his back for some time if placed so. The temperature -at this time was 102.6 deg.F. Both pupils, the one exposed to the light and -the one protected, were contracted. At 12.02 p.m. convulsive movements -of the legs appeared. The rabbit made one leap, the temperature rose to -103.6 deg.F., and after a few convulsive movements of the limbs the anus -relaxed and a small stool appeared, the pupils dilated, and the animal -died at 12.06 p.m. - -_Experiment No. 4._--The feeding of the extract of 464 grams induced a -fall in temperature of 2.4 deg.F. in three hours, and the rabbit died -several hours later (at night). - -_Experiment No. 5._--March 2, 1906, a rabbit weighing 928 grams was fed -with a concentrated extract of 500 grams of the fresh seeds and pods of -_Astragalus mollissimus_, made in September, 1905, and preserved with -chloroform water. This animal died in one hour and seven minutes. The -animal showed the usual post-mortem conditions. - -It was thus found that the aqueous extract of 500 grams of the fresh -_Astragalus mollissimus_ would cause death in about one hour in rabbits -weighing about 2 pounds (907 grams), these rabbits showing constant -clinical symptoms--urination, paralysis, more or less convulsive -muscular twitchings, often terminating in general convulsions, -drowsiness, and stupor, with more or less anesthesia. The pupils at the -time of death were often unequal. At first there was usually a slight -rise in temperature, but this was soon succeeded by a fall. Often there -were soft stools. The post-mortem lesions in these cases were marked -congestion, with hemorrhages in the stomach walls and a secretion of -thick mucus. The portions of the stomach walls most affected were the -dependent portions near the cardiac end. The intestines showed -dilatation of the blood vessels. The mesenteric vessels and also the -vessels in the cerebral portions of the dura were markedly dilated; in -some cases there were clots, especially at the posterior portion of the -brain, between the cerebrum and the cerebellum. At times there were -clots over the dorsal portion of the cord. On cutting into the brain the -brain substance itself did not appear to be congested. The cord seemed -about normal, but the vessels of its membranes were well marked. The -other organs showed nothing characteristic macroscopically. These -experiments were repeated many times and found to be constant. - -These acute symptoms were likewise produced by an extract of 500 grams -of the fresh _Aragallus lamberti_ from Arizona preserved in chloroform -water (rabbit weighing 1,998 grams). An aqueous extract of 150 grams of -the dried _Astragalus mollissimus_[155] from Imperial, Nebr. (1906), -caused death in one hour and fifty-eight minutes in a rabbit weighing -1,530 grams, and an extract of 100 grams killed in one hour and -twenty-two minutes a rabbit weighing 736 grams. - -An aqueous extract of 100 grams of the dried _Astragalus bigelowii_ -induced death in one hour and thirty-eight minutes, the rabbit weighing -1,502 grams. - -An aqueous extract of 150 grams of _Astragalus nitidus_ collected at -Woodland Park, Colo., in 1906 induced death in three hours and five -minutes, the rabbit weighing 1,672 grams. - -An aqueous extract of 200 grams of the dried _Astragalus bisulcatus_ -caused death after several hours (at night), the rabbit weighing 2,423 -grams. - -In certain cases this production of acute symptoms was not entirely a -question of salt action, as was shown by certain other experiments. In -other cases salt action seems to be the important factor, so that the -production of these acute symptoms can not always be considered -characteristic. - - * * * * * - -FOOTNOTES: - - [154] In all cases in which the plants were preserved with - chloroform sealed vessels were used for shipping. The - chloroform was carefully evaporated off in vacuo before - feeding the extract, the evaporation requiring several hours. - The plants were collected by Dr. C. Dwight Marsh, in charge - of the field investigations at Hugo, Colo. - - [155] All extracts from dried material were made at - Washington. - - -=CHRONIC CASES.= - -_Experiment No. 6._--February 19, 1906, a large gray rabbit weighing -2,055.3 grams was fed with 60 c.c. of fluid representing the -concentrated aqueous extract of 250 grams of the fresh _Astragalus -mollissimus_, collected September 18, 1905, and preserved in chloroform. -This rabbit was very hard to hold. The ears rested on the body. The -temperature at the time of feeding, 1.30 p.m., was 102.3 deg.F. At 2.57 p. -m. the animal looked dull but resisted handling. At 3.30 p.m. it -urinated. At 4.15 p.m. the temperature was 98.5 deg.F., the pupils were -about the same size as before feeding, and the animal became much -duller. The next day at 12.50 p.m. the temperature was 102.4 deg.F., and -at this time the animal could be handled with greater ease. The animal -ate in the morning. The same amount of extract was again fed at 1.24 p. -m. At 1.35 p.m. the animal was much duller and could be turned on his -back with ease. If disturbed he ran against the wall as if utterly -unconscious of the obstruction. The animal had soft, liquid, brown -stools and tried to lie down as much as possible. If turned on its back -with the feet up it would stay so almost indefinitely. Temperature, -103.8 deg.F.; respiration very rapid. At 2.40 p.m. the temperature was -99.8 deg.F., and the animal died a few minutes later. After death the -pupils were much contracted. The vessels of the dura covering the brain -were much dilated, but the vessels inside the brain were not dilated. -The stomach walls were congested and marked with numerous petechiae and -covered with mucus. - -_Experiment No. 7._--On February 19, 1906, a white and brown rabbit -whose temperature was 103.2 deg.F. was fed 30 c.c. of aqueous fluid -representing the concentrated extract of 125 grams of the fresh -_Astragalus mollissimus_, collected September, 1905, and preserved with -chloroform. The rabbit weighed 1,502.5 grams. This extract was fed at -1.45 p.m., and at 4.15 p.m. the temperature was 102.6 deg.F., but there -were no marked symptoms. The following day at 2.04 p.m. the temperature -registered 102.5 deg.F. The same amount of extract was given at 2.09 p.m. -The temperature at 4 p.m. was 99.8 deg.F., the animal was dull, and the -pupils were perhaps a little smaller. The animal could not be turned -over without resistance. The following day, February 21, at 1.30 p.m. -the temperature was 102.6 deg.F., and at 1.45 the same amount of extract -was given. At 1.54 p.m. the animal was much duller and the breathing -was very rapid. At 4.10 p.m. the temperature was 101.3 deg.F. The animal -had been dull ever since the feeding was begun. It nibbled food shortly -before the last feeding. On February 23 the same amount of extract was -given at 2.16 p.m., temperature 99 deg.F. The breathing was very rapid, -the ears shaking, and there was a sleepy, dull look about the animal. At -3.30 p.m. the animal was dull, but would still walk about if disturbed. -At this time the animal weighed 1,445.8 grams. At 4.30 p.m. the -temperature was 102 deg.F. and the pupils were about normal size. There was -a marked sleepy look about the animal, which sat quietly in its cage. - -February 24, at 1 p.m., the animal was very dull and could with ease be -turned on its back with its feet in the air. It would sit in its cage -perfectly quiet. The weight at this time was 1,417.5 grams, the -temperature 96.6 deg.F. On February 26 the animal weighed 1,360.8 grams. It -was dull and refused to eat. The abdomen felt very distended and -tympanitic. February 27 the weight was still 1,360.8 grams, and the -animal sat in its cage as if asleep, with eyes half closed. There was no -diarrhea and the abdomen was very distended. At 11.15 a.m. there was a -general convulsion and the animal fell over. At 12 m. the abdomen seemed -even more swollen, the animal was hardly able to walk, and it fell over, -uttering a cry. Pupils were about normal--perhaps a little smaller. The -animal died at 12.10 p.m. - -The post-mortem, made immediately after death, showed the abdomen -markedly tympanitic, and the large intestines could be outlined through -the abdominal walls with ease. The large intestines were of a chocolate -color, intensely congested, and marked with hemorrhages. On opening the -abdomen there was a decided putrefactive odor, and about an ounce of -bloody fluid was found in the peritoneal cavity, together with fibrin -flakes. The stomach was pale, the first three inches of the small -intestine up to where it turned sharply were pale, and below this the -intestines were injected and full of gas and of a dark red color. The -kidneys were 3-1/2 centimeters long and were pale, capsules easily -peeled off; cortex pale. Liver pale and infected with some coccideae. The -gall bladder was one-quarter inch wide and one inch long. Spleen a -trifle pale; lungs pale, nothing abnormal; heart relaxed. On opening the -stomach gas and fluid, with some food, exuded. The walls were pale, but -pink in some places. There was no marked congestion or hemorrhage or -perforation. The mesenteric vessels were dilated. The upper portion of -the intestines contained a little mucus-like fluid, but lower down -became bloody, and still lower contained pus-like fluid. The walls were -hemorrhagic. The large intestine contained a soft, fecal-like fluid, -very foul. Its walls were much congested and full of hemorrhagic points. -The cortex of the suprarenal bodies was sharply defined, the medullae -brownish. Brain pale, some dural vessels well marked, no clots or -hemorrhages. Base of brain pale. No congestion seen on cutting into the -brain. Spinal cord showed no hemorrhages or lymph effusions. - -_Experiment No. 8._--On February 18, 1906, at 2 p.m., a rabbit whose -temperature was 102.2 deg.F. was fed with the aqueous extract of 125 grams -of fresh _Astragalus mollissimus_, collected in September, 1905, and -preserved in chloroform, 30 c.c. of the fluid being used. At 4.25 p.m. -the temperature was 102.4 deg.F. No symptoms were noted. This rabbit -weighed 1,644.3 grams. On February 20 at 2.09 p.m. the temperature was -102.2 deg.F. and the rabbit showed no symptoms. The same dose was repeated -at 2.15 p.m. At 4 p.m. the temperature was 100.3 deg.F. The rabbit was -dull but could not be turned over without a struggle. February 21 at -1.30 p.m. the temperature was 101.4 deg.F. The same amount of extract was -fed at 1.45 p.m. At this time the animal was dull and breathed more -rapidly. At 4.10 p.m. the temperature was 97.3 deg.F. Next day the same -amount of extract was again given at 2 p.m. At 2.16 p.m. the breathing -became rapid and the animal duller. The ears were directed forward. At -4.15 p.m. the temperature was 101.6 deg.F.; weight 1,757.7 grams; animal -slightly dull. February 24, temperature 102 deg.F., weight 1,786 grams. -March 5, weight 1,729.3 grams. The animal was fed at 3.20 p.m. with a -concentrated extract of 125 grams of _Astragalus mollissimus_, collected -in September. Temperature at time of feeding 100.4 deg.F.; 3.40 p.m., no -symptoms; 4 p.m., temperature 102 deg.F. March 7, weight 1,644.3 grams; -March 8, weight 1,672.6 grams; March 10, weight 1,701 grams; March 12, -weight 1,658.4 grams; March 14, weight 1,701 grams. - -In this case, where the same dose was given in a period of five days, -very little effect on the rabbit was noted. - -_Experiment No. 9._--On March 1, 1906, a black rabbit weighing 2,664.8 -grams was fed with a concentrated aqueous extract of 250 grams of fresh -_Astragalus mollissimus_, collected in the fall of 1905. - -On March 5 the weight was 2,296.3 grams. The animal was then given the -same amount of extract. During the afternoon it passed mucus and thick -pieces of feces and was dull; respiration very rapid. March 6, weight -2,282 grams; March 7, 3 p.m., animal very dull and would not eat; sat -hunched up, but resisted being disturbed: weight 2,310.5 grams. March 8, -weight 2,183 grams; March 9, weight 2,069.5 grams. Pupils dilated; -finger could be run almost against the eye, provided the lashes were not -touched, without the animal winking or paying any attention. Rabbit ate -very little and had not urinated since the preceding day. Left ear had -fallen to the side as if the animal were unable to support it. Weight, -1,912.8 grams. From March 9 to March 11, 67 c.c. of cloudy urine were -voided. This did not clear with acetic acid. Left eye tearing. March 10, -head held to right side. March 12, weight 1,786 grams. Left pupil -smaller than right, neither responding to light. Rabbit very weak. March -14, weight 1,729.3 grams. Would not eat. March 16, weight 1,644.3 grams. -Right pupil larger than left, neither responding to light. Diarrhea -present. Breathing noisy. In sitting down she raised herself on her -forelegs, evidently to take the pressure off her abdomen, which was -distended. If disturbed, she would butt against the side of the cage, -apparently oblivious of its presence. Knee jerks were very active, -almost a clonus. Reflex from tendo Achillis active. March 17, forelegs -spread out, head falling to left side. The temperature had fallen below -94 deg.F. and would not register on the ordinary clinical thermometer. The -ears twitched, the head was thrown back, the abdomen was distended, and -the rabbit gritted its teeth. Died. Weight, 1,559.2 grams. - -Brain and spinal cord pale. Dural vessels plainly seen but not marked. -Intestinal vessels congested. Stomach pale; nothing apparent -macroscopically save a small pin-point ulcer.[156] Heart relaxed. -Post-mortem examination otherwise negative macroscopically. - -_Experiment No. 10._--A mouse-colored rabbit weighing 1,927.8 grams was -fed February 18, 1906, at 2.26 p.m., with a concentrated aqueous -extract of 250 grams of fresh _Astragalus mollissimus_ collected in -September, 1905, and preserved in chloroform water. The temperature of -this rabbit was 102.6 deg.F. The fluid given was 40 c.c. At 2.45 p.m. the -rabbit urinated and at 2.57 p.m. was dull and the respiration became -rapid. The animal then aborted and had three young, two of which showed -some movement after birth, but were apparently premature. - -On February 23 the temperature of this rabbit was 102.9 deg.F. at 1.40 p. -m. She was then fed with the same amount of the extract as before. At -2.16 p.m. she lay down and became much duller; left ear fallen to side. -At 3.30 p.m. the rabbit was unable to stand. The pupil of the eye -exposed to the light was dilated. The animal died without a struggle. -The stomach contained much bloody mucus. In the dependent portion of the -stomach near the cardiac end were marked petechiae in the walls, with -bright-red blood in the stomach itself. The heart was relaxed. The -intestines showed nothing abnormal. The dural vessels of the brain were -dilated; there was a clot on the dura over the fourth ventricle. Spinal -cord and kidneys normal, the capsules not adhering. Weight, 1,786 grams -at death. - -_Experiment No. 11._--On March 1, 1906, a rabbit weighing 2,126.2 grams -was fed with a concentrated aqueous extract of 250 grams of the fresh -_Aragallus lamberti_ preserved in chloroform water. On March 5 this dose -was repeated, 37.5 c.c. of the fluid being used. March 6 the rabbit -weighed 1,956 grams; March 7, 1,913.6 grams; March 8, 1,828.5 grams; -March 9, 1,701 grams; March 12, 1,672.6 grams; March 14, 1,644.3 grams. - -_Experiment No. 12._ January 19, 1906, a concentrated aqueous extract of -500 grams of the fresh _Aragallus lamberti_ preserved with chloroform -water was fed to a rabbit weighing 785 grams. The temperature at 12.10 -p.m., the time of feeding, was 101.6 deg.F. The temperature 1 hour and 43 -minutes later was 94.6 deg.F., and the animal died shortly after, showing -the same condition as occurred after feeding extracts of _Astragalus -mollissimus_. - - * * * * * - -FOOTNOTES: - - [156] Compare Ploenius, W., Beziehungen d. Geschwuers u. d. - Erosionen d. Magens z. d. funktionell. Stoerungen u. Krankh. - d. Darmes, Arch. f. Verdauungsk., vol. 13, pp. 180, 270, - 1907, and Tixier, L., Anemies Exper. Consec. aux Ulcer. du - Pylore, Comp. Rend. Hebd. Soc. de Biol., vol. 62, p. 1041, - 1907. - - -=PREGNANT ANIMALS.= - -_Experiment No. 13._--A large, gray, pregnant rabbit weighing 2,891.6 -grams was fed on February 22, 1906, with 42 c.c. of fluid, -corresponding to the aqueous extract of 250 grams of _Astragalus -mollissimus_ collected in September and October, 1905, and preserved -with chloroform. At 4 p.m. the animal was dull, but still resisted -efforts to handle. On February 24 this animal weighed 2,778.2 grams, and -on February 26 it bore a litter of seven young rabbits. One or two of -these showed movements of the limbs, but were apparently immature. This -rabbit on March 10 weighed 2,537.3 grams; March 12, 2,438 grams; March -14, 2,508.9 grams; March 22, 2,494.7 grams. - -_Experiment No. 14._--On March 1, 1906, a black rabbit weighing 2,721.6 -grams was fed at 12.15 p.m. with a concentrated aqueous extract of 250 -grams of the fresh _Astragalus mollissimus_ collected in September, -1905. On March 2 it weighed 2,438 grams; at 2.58 p.m. it still resisted -efforts to turn it on its back; at 3.15 p.m. it could be turned on its -back with ease. March 6 the weight was 2,338.8 grams; March 7 the -animal was very dull, would not eat, pupils dilated, hind legs -paralyzed; died during the night; weight, 2,267.9 grams. - -The stomach walls were pale save at the dependent portion near the -cardiac end, where there was a hemorrhagic, ulcerated area about 1-1/2 -by 1-1/2 inches. The intestines were full of gas, but not hemorrhagic. -The uterus contained eight immature foeti. The uterine walls were -hemorrhagic. The kidneys weighed 9-1/2 grams; their medullae were dark -and the straight tubules well defined. The cerebral dural vessels were -congested and the spinal dural vessels were well defined. The bladder -was found contracted. The blood gave no bands for methaemoglobin, but -showed merely those of oxyhaemoglobin on spectroscopic examination. - -_Experiment No. 15._--Control experiments made by feeding water were -negative, except when a large quantity (150 c.c.) of water was given to -a rabbit weighing 1,020.5 grams. The animal died in 12 hours with marked -pallor of the tissues (hydraemia), a pathological condition quite -different from that obtained by feeding extracts of the loco plants, and -no such results were secured with the amount of water used in our -feeding experiments, 50 to 70 c.c. - - -=SUBCUTANEOUS INJECTIONS.= - -_Experiment No. 16._--On February 28, 1906, a white rabbit weighing -581.2 grams was injected subcutaneously at 10.35 a.m. with a -concentrated aqueous extract of 83 grams of fresh _Astragalus -mollissimus_ collected in September, 1905, and preserved with -chloroform. The temperature before injection was 102.1 deg.F. At 1.40 p.m. -the animal was dull; at 3.12 p.m. the temperature registered 99.8 deg.F. -The animal died during the night. The post-mortem examination was -negative. Stomach pale; heart relaxed save left ventricle, which seemed -contracted; dural vessels of the brain dilated; kidneys perhaps normal. -No microscopical examination. - -_Experiment No. 17._--February 28, 1906, at 10.25 a.m., a guinea pig -weighing 496 grams was injected subcutaneously with a concentrated -aqueous extract of 83 grams of the fresh _Astragalus mollissimus_ -preserved in chloroform water. At 1.40 p.m. there was muscular -twitching. The animal was dull and could be easily turned on his back. -The hind legs began to show weakness. At 1.50 p.m. the hind legs were -almost completely paralyzed and the animal could be easily turned on his -back. Muscles of the limbs twitched and semen was expelled. Animal died -at 2.15 p.m. - -Post-mortem showed dural vessels of cord and brain full of blood. -Stomach pinker than normal: mesenteric vessels dilated. Heart almost -empty of blood. Kidneys congested. - - -=SUMMARY OF FEEDING EXPERIMENTS ON RABBITS.= - -These experiments indicate that an acute form of poisoning may be -induced by feeding concentrated aqueous extracts of _Astragalus -mollissimus_ and _Aragallus lamberti_ from Hugo, Colo., and Imperial, -Nebr., to rabbits, and that if the extract is given in smaller and -repeated doses a more prolonged or chronic condition may follow. - -The rabbits showing the chronic effects of these plants exhibit symptoms -which have a marked parallelism with those reported as occurring in -larger herbivora (horses and cattle) on the range when locoed; that is, -the loss of appetite (Experiment No. 9), the emaciation and loss in -weight (Experiment No. 9), the dullness and stupor, with more or less -anesthesia (Experiment No. 7), the disturbance in the visual function -(Experiment No. 9), and the mental symptoms (Experiment No. 6). The -occasional abortion compares with what has been observed in larger -animals. The dried _Astragalus mollissimus_ and _Aragallus lamberti_ -still retained their poisonous properties, as we were able to kill with -aqueous extracts of the dried plants made in the laboratory under the -proper conditions. - - -=EXPERIMENTS ON SHEEP.= - -_Experiment No. 1._--On May 31, 1906, a sheep weighing 32.2 kilos was -fed with a concentrated aqueous extract of 1,000 grams of the fresh -_Astragalus mollissimus_ preserved in chloroform water. The temperature -at 11 o'clock, the time of feeding, was 103.4 deg.F. At 11.45 a.m. this -dose was repeated. At 12 o'clock the temperature was 104.1 deg.F. At 12.45 -the animal urinated. At 1.10 p.m. a similar extract of 2,000 grams was -fed. The total liquid used was 1,500 c.c. On June 1 no symptoms were -noted. On June 5 an extract of 3,000 grams of fresh _Aragallus lamberti_ -and 3,000 grams of _Astragalus mollissimus_ was fed. After feeding this -the animal could be easily turned over on its back and its ear pricked -with impunity. The animal at this time weighed 30.8 kilos. On June 6, at -11 a.m., the temperature was 104 deg.F. The sheep had numerous soft -stools, and was very dull, and would not eat. On June 7 the temperature -was 103.7 deg.F. and the sheep still refused to eat. On the 8th the -temperature was 103.2 deg.F. at 10.40 a.m., and the stools were still -numerous and soft. - -There were then fed 640 c.c., representing the aqueous extract of 4,000 -grams of the fresh _Aragallus lamberti_. The animal could be easily -turned on its back. It weighed at this time 28.57 kilos. On June 9, at -10.47 a.m., the temperature was 103.4 deg.F. The sheep still did not eat, -but had no diarrhea. It now weighed 27.9 kilos, and the temperature was -103 deg.F. at 10.45 a.m. - -On June 13 the animal began to eat, and 1,700 c.c. of fluid, -representing 5,500 grams of the fresh _Aragallus lamberti_, were fed. -The temperature at 12.30 p.m. was 103 deg.F. On June 14 the temperature -was 103.4 deg.F., the animal weighed 28.3 kilos, and refused food. On June -16 the weight was 28.3 kilos; the temperature at 2 p.m. was 103.5 deg.F. -There was no diarrhea. - -On June 19 the aqueous extract of 1,000 grams of the dried _Astragalus -mollissimus_ was fed with 420 c.c. of water. The temperature was 102.6 deg. -F. On June 20 the temperature was 102.9 deg.F. at 10.45 a.m. - -On June 21 500 c.c., representing the aqueous extract of 1,000 grams of -the dried _Astragalus mollissimus_, were again fed. The animal now -weighed 26.9 kilos. On June 26 the animal weighed 26 kilos, and its gait -was very uncertain. The temperature was 104.2 deg.F. It was fed 300 c.c. -of fluid, representing the extract of 400 grams of the dried _Astragalus -mollissimus_. On June 29 the animal weighed 26.8 kilos and the -temperature was 102.8 deg.F. It was fed the extract of 1,000 grams of dried -_Astragalus mollissimus_ in 500 c.c. of water. On June 30, at 10.45 a. -m., the temperature was 104.2 deg.F. The animal was very dull and died at -night. - -At autopsy the intestines and stomach merely appeared pale. There were -no worms, and the lungs and other organs appeared normal. - -_Experiment No. 2._--A lamb weighing 15.4 kilos was fed on July 6, at -1.10 p.m., with 640 c.c. of fluid, representing the extract of 2,000 -grams of _Astragalus mollissimus_. At 1.17 p.m. the animal could be -turned on its back, and it regained its feet with difficulty. At 1.24 p. -m. it urinated and had a stool. The lamb died during the night. - -The autopsy the following morning showed the heart filled with clots; -lungs normal save for hypostatic congestion. The cerebral and dural -vessels were dilated. About 1-1/2 teaspoonfuls of bloody serum were -found at the base of the brain. There was none in the lateral -ventricles, and no clots. The kidneys exhibited no marked congestion. -There was no fluid found in the peritoneal or the pleural or pericardial -cavities. The first stomach, however, contained small hemorrhagic spots, -and the second was black. There were small hemorrhages in the -intestines. - -_Experiment No. 3._--July 13, 1906, a sheep weighing 19.5 kilos was fed -with 640 c.c. of fluid, representing the extract of 2,000 grams of -_Aragallus lamberti_. The temperature at the time of feeding, 1.10 p. -m., was 105.3 deg.F. At 1.49 p.m. the sheep could be easily turned on its -back. At 2.23 p.m. the temperature was 103.6 deg.F. At 3.42 p.m. the -temperature was 103.5 deg.F. At 4.20 p.m. the respiration was fairly -rapid. On July 14, at 11.15 a.m., the temperature was 103.6 deg.F. The -sheep would run about but could easily be turned over. It had not eaten, -but there was diarrhea present. July 15, at 3.30 p.m., the temperature -was 104 deg.F. The animal had eaten. On July 17 the temperature was 104 deg.F. -and the animal weighed 18.8 kilos. On the 27th it weighed 17.2 kilos; on -August 29, 20.8 kilos. - -_Experiment No. 4._--A lamb weighing 19 kilos was fed August 21, 1906, -with 740 c.c., representing the aqueous extract of 2,500 grams of the -fresh _Astragalus mollissimus_, shipped to Washington in September, -1905. This animal ate at night, but the following day was dull. When -seen on August 27 there was diarrhea present and the animal was still -dull. On the 28th the animal died, weighing 16.7 kilos. There was no -autopsy on account of decomposition. - -_Experiment No. 5._--A lamb weighing 15.6 kilos was fed on September 4, -1906, with an aqueous extract representing 3,500 grams of the dried -_Aragallus lamberti_, 1,000 c.c. of water being used. The temperature -at the time of feeding was 104.3 deg.F. At 2.48 p.m. the animal on rising -to its feet developed a slight tremor of the fore legs and showed marked -disinclination to stand on its feet. The temperature was 104 deg.F. The -animal died at 4.25 p.m. The post-mortem was negative, save for some -reddening of the second stomach.[157] - -These feeding experiments in sheep can not be considered quantitative, -because, as is shown later, aqueous extracts of dried plants are often -inactive, yet poisonous principles may be obtained from the plants by -treatment with digestive fluids. - -Extracts of dried loco plants vary much in their toxicity; with some the -writer was unable to kill rabbits, even when an extract of 300 grams of -the dried plant was used. It is interesting to note that when the field -station was established at Hugo, Colo., in 1905, almost all the aqueous -extracts of dried specimens sent to Washington would produce the acute -symptoms of poisoning in rabbits, but during the third season of its -existence many of the samples sent from the same area were much less -active, if not inactive. - - * * * * * - -FOOTNOTES: - - [157] There was a slight odor of chloroform noticed on - opening the stomach, so that perhaps the imperfect removal of - the chloroform due to a hurried evaporation of the extract - should be taken into consideration in this case. - - - - -=LABORATORY EXPERIMENTS--CHEMICAL.= - - -The fact that the aqueous extract of 500 grams of the fresh _Astragalus -mollissimus_, or of 200 grams (in some cases 100 grams) of the dried -plant, when fed by mouth, would regularly kill a rabbit weighing about -907 grams, with certain definite clinical symptoms and pathological -lesions, was at first arbitrarily selected as our test to aid in the -isolation of the active principle. Later the production of chronic -symptoms by the aqueous extract or digestion of 200 grams of these dried -plants given in doses of 100 grams each on two successive days was -considered essential. Carnivora, such as dogs and cats, vomit so easily -as to render them unsuitable for these investigations. The aqueous -extract was distilled with and without steam, also after acidifying with -sulphuric acid, and likewise after the addition of magnesium oxid, but -in all cases the distillate was inactive. - -The concentrated aqueous extract was shaken by the Dragendorff method -with petroleum ether, benzol, chloroform, ether, and amyl alcohol, both -in alkaline and acid condition, but the shakings yielded no -physiologically active body. Shakings by the Otto-Stas method also -proved inactive. Lead acetate, lead subacetate, silver nitrate, mercuric -chlorid, alcohol, phosphotungstic acid, trichloracetic acid, ammonium -hydrate, sodium carbonate, sodium hydrate, Mayer's solution, uranyl -acetate, silver oxid, and barium carbonate also failed to remove the -active constituent. They gave heavy precipitates in all cases, but these -proved inactive. Hydrocyanic acid was sought for with negative results. -The pathological lesions in the very acute cases suggested in some -respects oxalic acid, a saponin, a metal, or perhaps a toxalbumin as the -active principle, but none of the precipitants for saponins, such as -lead and copper, or the magnesium oxid method yielded a body which was -active. Proteids were excluded by the fact that the various proteid -precipitants--alcohol, trichloracetic acid, lead subacetate, mercuric -sulphate or chlorid, and salting out with ammonium sulphate and sodium -chlorid (complete saturation and half saturation)--failed to give an -active precipitate. Glucosidal or alkaloidal bodies were also excluded. -On dialysing for twenty-four hours, some of the active principle went -into the dialysate and some remained in the dialyser. Ether yielded a -precipitate from alcoholic solution which failed to kill. The -possibility of the activity of the plants being due to its normal -acidity was excluded by neutralizing the extract with sodium hydrate and -precipitating the salts with alcohol. The filtrate proved active after -removing the alcohol. - -The negative results in looking for active alkaloidal, or glucosidal, or -proteid bodies suggested that perhaps the action was due to some -inorganic constituent. The writer then boiled the extract three minutes -and as the filtrate was still found active and the proteid precipitate -inactive became convinced of the inorganic nature of the active -constituents, and finally incinerated the plant. The acid extract from -this was also active, but death was delayed several hours. This was -believed to be due to the insoluble form into which the compound was -converted.[158] In fact, the question of solubility and the avoidance of -an acid reaction, which of itself may kill, are the main points to keep -in mind. - -These experiments indicated that the injurious action toward rabbits of -the _Astragalus mollissimus_ and _Aragallus lamberti_ collected at Hugo, -Colo., was due to one or more inorganic constituents,[159] but it does -not follow that all loco plants have the same poisonous principle nor -that the same species occurring on all soils has the same poisonous -action.[160] - -Of _Astragalus mollissimus_ from Imperial, Nebr., collected in 1906, 200 -grams were ashed in a platinum bowl and extracted with water. This -aqueous extract when neutralized produced no marked symptoms in a rabbit -and the weight of the animal remained about the same. - -The ash undissolved after this extraction was then treated with acetic -acid and water overnight, and after carefully evaporating off the acetic -acid on the bath (tested by litmus paper) the residue was fed, partly in -solution and partly suspended in water, to a rabbit weighing 1,800.2 -grams. Next day the rabbit weighed 1,771.8 grams, showed paralysis of -the limbs, and died during the morning. The stomach was intensely -reddened and contracted. - -An extract of a similar ash was made by boiling the same amount with a -large quantity of 94 per cent alcohol. This was evaporated in vacuo and -taken in water and fed to a rabbit weighing 1,459.9 grams. On the sixth -day the animal died, having lost 70.9 grams in weight. The stomach -showed reddening but no ulcers. - -An acetic acid aqueous extract, made from the ash after the alcoholic -extraction, proved inactive, showing that the alcohol had removed the -active bodies. A 70 per cent alcohol extract of another ashed lot proved -active, killing the rabbit overnight. - -Of _Astragalus mollissimus_ from Imperial, Nebr., 200 grams were ashed -in a platinum bowl and the ash treated with acetic acid water. After -freeing from acid, one half of the solution and emulsion was fed one day -and the second half fed the following day. The rabbit at the time of -feeding weighed 1,275.7 grams. Fourteen days later the animal died, -weighing 1,105.6 grams. No autopsy. - -A similar extract of the ash from between 100 and 150 grams of the same -dried plant produced death in a rabbit weighing 1,190 grams in two hours -and fifty-eight minutes. - -The acetic acid extract of the ash of 125 grams of a mixture of the -dried _Astragalus mollissimus_ and _Aragallus lamberti_ received from -Hugo, Colo., June, 1907, after freeing from acid, was fed to a rabbit -weighing 1,304 grams on July 29. On July 30 it weighed 1,332.4 grams. -August 1 it weighed 1,219 grams, and it died the same day. The stomach -was reddened and showed ulcers. - -A similar extract from 250 grams of the same dried plants on boiling -gave a heavy precipitate, but this precipitate was inactive, while the -filtrate killed a rabbit in four hours. - -Of dry _Aragallus lamberti_ collected in September, 1906, 200 grams were -extracted with water and fed to a rabbit weighing 1,516.7 grams. Two -days later the animal weighed 1,360 grams and died the same day. - -The ash from 200 grams of the same dried plant was extracted with acetic -acid, and after evaporating off the acid this was fed to a rabbit -weighing 2,045.3 grams. Seven days later the animal weighed 1,729.3 -grams, having lost 316 grams in weight. - -The ash from 250 grams of the same species of plant, after similar -treatment with acetic acid, induced death in a rabbit weighing 2,069 -grams in 2 hours and 20 minutes. The stomach was inflamed. - - * * * * * - -FOOTNOTES: - - [158] Work is now being done by the writer on the inorganic - constituents of various plants. - - [159] Scattered throughout the veterinary literature one - finds cases of poisoning in animals with symptoms similar to - those occurring in locoed animals which are attributed to - eating plants grown on a peculiar soil, as in Oserow, Ueber - Krankh. d. Pferde, welche Aehnlichkeit mit der Cerebro-spinal - meningitis haben, aber durch Vergiftungen mit Graesern von - Salzgruenden (Salzmooren) verursacht werden, Journ. f. Allgem. - Veterinaer-Medicin, St. Petersburg, p. 486, 1906. Abstract in - Jahresber. ueber d. Leistungen auf dem Gebiete d. - Veterinaer-Medicin, vol. 26, p. 226, 1906.--Compare also Etude - sur Quelques Plantes Veneneuses des Regions Calcaires, Bul. - Soc. Cent. de Med. Vet., vol. 48, p. 378. 1894. - - [160] After completing this work the writer found that Sayre - had said that he "had the suggestion that the harm coming - from this plant is due to the inorganic constituents; this - clue has been followed up, but like the others has brought us - no nearer to the solution of the problem." Kans. Acad. Sci. - Trans., vol. 18, p. 144. 1903. - - - - -=EFFECT OF THE AQUEOUS EXTRACT OF ASHED LOCO PLANTS.= - - -The filtrate from the ash from 200 grams of dried _Astragalus -mollissimus_, from Imperial, Nebr., after similar treatment with acetic -acid water and freed from free acid, killed a rabbit in several hours. - -Hydrochloric acid also rendered the toxic agent of the ash soluble in -water, but proved unsuitable for our work, as it was found impossible to -obtain neutral residues by mere evaporation on the bath. At first one of -the heavy metals or members of the H_{2}S group[161] was suspected, but -on passing H_{2}S into the slightly acid extract of the ash no active -precipitate resulted, but the filtrate remained active.[162] A special -Marsh test was, however, made for arsenic and antimony with negative -results. A test for tungsten with zinc and hydrochloric acid proved -negative. - -Members of the ammonium sulphid group were then suspected, but while -ammonium hydrate alone gave a heavy white precipitate, this precipitate, -as also the black one with ammonium sulphid, proved inactive save when -not thoroughly freed from acid (used for solution). The action of this -ammonium sulphid precipitate on rabbits was watched for sixteen days, -but without result. Nevertheless, the writer still suspected some of the -rare earths.[163] - -Sestini[164] had found that if certain plants were nourished with a -solution of a beryllium salt, in the ash of these plants could be shown -the presence of beryllium. - -Two grams of beryllium chlorid were fed in aqueous solution to a rabbit -weighing 1,800.2 grams. In four days this animal lost 241 grams and -died. The stomach showed the same general pallor seen in chronic locoed -rabbits, but no ulcers. The tests for beryllium by Sestini's method, -however, failed to show beryllium in the active loco plants examined. - -Thorium chlorid, cerium chlorid, and lanthanum chlorid in 2-gram doses -and zirconium chlorid in 3-gram doses produced no chronic symptoms in -rabbits or, in fact, any disturbance. Titanium chlorid, 2.5 grams, -evaporated in the air and then fed in an emulsion to a rabbit, also -proved inactive, but this inactivity may have been due to its -insolubility. - -Thallium nitrate c. p., in aqueous solution, in 2-gram doses, killed a -rabbit weighing 2,154.6 grams in two hours and fifteen minutes. The -stomach in this case, while pink, was not hemorrhagic. - -Zirconium chlorid has an astringent taste, and if fed repeatedly will -cause the metallic astringent action. On boiling an acetic acid solution -of the ash with sodium acetate a precipitate formed.[165] - -The presence of zirconium was thus suspected and Dr. E. C. Sullivan, of -the United States Geological Survey, estimated it to be present in the -ash of a sample of _Aragallus lamberti_ in about 0.01 per cent zirconium -oxid, with also 0.1 per cent titanium dioxid.[166] - -Zirconium chlorid, 3 grams, was fed in aqueous solution to a rabbit -weighing 850.5 grams. This rabbit lost 96 grams in seven days, and was -then fed 3 grams more of the same solution and the following day 2 grams -more. It died eight days later, weighing 656 grams. The stomach and -intestines were contracted, but showed no ulcers. However, 4 grams -killed a rabbit in two hours and thirty-two minutes. - -The filtrate, after treating an active solution of the ash with hydrogen -peroxid, proved active, thus showing that zirconium was not entirely -responsible for the poisonous action. - -Yttrium, while not found in the plant, was administered as yttrium -chlorid to a rabbit weighing 1,530 grams in 2-gram doses in solution. -This animal gained 113.4 grams in five days. - -Didymium chlorid c. p., in 3-gram doses, was fed to a rabbit weighing -1,020 grams. This rabbit lost 70 grams in four days. - -The administration of manganese acetate[167] in 2-gram doses was -followed by a gain in weight of a rabbit of 42.5 grams, while a dose of -3 grams killed a rabbit weighing 1,077 grams in two hours and thirty -minutes. Wohlwill[168] has emphasized the fact that the members of the -iron group owe their comparative harmlessness to not being absorbed by -the gastro-intestinal tract. - -No zinc was found in the plant.[169] - -It is well recognized that potassium salts given hypodermically are -decidedly toxic and that ammonium salts given per os will kill, so that -the writer considered the possibility of other members of the group -being responsible for the injurious action. The fact that the alkaline -distillate of the plant proved inactive eliminated the ammonium salts. - -Caesium chlorid c. p., 2 grams, was fed in aqueous solution to a rabbit -weighing 1,077.2 grams. In six days this animal lost 255 grams in -weight, when it died.[170] - -A second rabbit, weighing 1,020.5 grams, was fed with 2 grams of the -same solution and lost 368 grams in twenty-one days. The spectroscopic -test, however, failed to show caesium in the ashed plant. Rubidium -chlorid c. p., in 2-gram doses, proved inactive. The platinum chlorid -precipitate from the extract of the plant proved inactive. - -The fact that the filtrate after precipitation of the phosphates by tin -and nitric acid and H_{2}S was active excluded the phosphoric acid -radical, and the filtrate after treatment with BaCO_{3} and AgO being -active excluded the H_{2}SO_{4} and HCl radicals as the toxic body. -Fluorine was proved to be absent. - -A radio-active substance was suspected, but Dr. L. J. Briggs, Physicist -of Bureau of Plant Industry, reported that the dried plant showed no -special amount of radio-activity.[171] - -Power and Cambier, Sayre, and Kennedy had previously called attention to -the abundance of calcium in the plant, and the writer's investigations -confirm this. Pharmacologists are averse to believing calcium given per -os poisonous. The writer has, however, fed 5 grams of the acetate of -calcium in solution to a rabbit weighing 652 grams. This animal died in -two hours, with marked irritation of the stomach, the result being due -to the so-called "salt action." Much larger amounts were fed in divided -doses, but without injury. Calcium phosphate and calcium sulphate in -2-gram doses proved harmless to a rabbit weighing about 1,400 grams. -Three grams of magnesium acetate[172] were fed in solution for five -successive days to a rabbit weighing 1,417 grams, but without apparent -effect. - -Strontium acetate c. p., in 2-gram doses, likewise caused no -disturbance.[173] No strontium in any amount recognizable by chemical -tests was proved in the plant. So that by a process of exclusion the -writer was forced to think of barium as the main cause of the trouble. - -The writer noted that if the ashed plant was extracted with H_{2}SO_{4} -water and this extract freed from sulphuric acid with PbCO_{3} and -H_{2}S the solution proved inactive to rabbits and also that after this -extraction the acetic acid extract of the ash failed to kill. In other -words, the sulphate of our body was insoluble in water. At times in -passing H_{2}S into active solutions of the ashed plant freed from the -acetic acid by evaporation the filtrate and likewise the precipitate -were inactive. Noyes and Bray[174] have noted that if H_{2}S is passed -into certain solutions in the presence of an oxydizing agent, such as -ferric iron, H_{2}SO_{4} would be formed, which would throw any barium -out of solution. - -In one blood-pressure record made with a dog (vagi nerves cut), a rise -in blood pressure (a characteristic physiological action of barium) was -seen to follow the intravenous injection of the aqueous extract of the -plant, in spite of its normal acid reaction. - -Accidentally the writer found that Sprengel[175] had reported the -presence of barium in _Astragalus exscapus_, a closely allied plant. -Barium has also been found in the vegetable world by Scheele in 1788, -and later by Eckard,[176] who found it in beech, while Forchhammer[177] -proved it in birch, and Lutterkorth found it in the soil of the same -area in which Eckard worked. Dworzak[178] noted the occurrence of traces -of this element in wheat grown along the Nile, and Knop[179] found it in -the soil. Doctor Balfour, of Khartum, Egypt, informed the writer that he -knew of no cases in which this barium in wheat had produced poisoning. -Hornberger[180] found barium both in the red beech grown in Germany and -in the soil on which these trees grew. It has also been claimed that -various marine plants may take up barium from the sea.[181] - -Hillebrand[182] has called attention to the fact that the igneous rocks -of the Rocky Mountains showed a higher percentage of barium than rock -from other portions of the United States, so that under these conditions -one might expect the presence of barium in plants growing in this -region. A sample of _Aragallus lamberti_ and one of _Astragalus -mollissimus_ were sent to the Bureau of Chemistry for spectroscopic -examination for various elements and they reported traces of barium in -each.[183] - -With these arguments the writer felt sure of the presence of barium, and -the matter was discussed with Dr. E. C. Sullivan, of the United States -Geological Survey, and he kindly corroborated the conclusions reached as -to the presence of barium, controlling its presence by means of the -spectroscope, and estimated it roughly as 0.1 per cent BaO in the ash of -a sample of _Aragallus lamberti_ (6.3 milligrams BaSO_{4} in 4 grams -ash). This determination was made by Hillebrand's method. - -Kobert has anticipated this result, saying that "all plants are in the -position occasionally to take up barium combinations from the soil," and -"the plants which thus contain barium may act injuriously to men and -animals."[184] - - * * * * * - -FOOTNOTES: - - [161] Swain, R. E., and Harkins, W. D. Arsenic in Vegetation - Exposed to Smelter Smoke. Journ. Amer. Chem. Soc., vol. 30, - p. 915. 1908.--Harkins, W. D., and Swain, R. E. The Chronic - Arsenical Poisoning of Herbivorous Animals. Journ. Amer. - Chem. Soc., vol. 30, p. 928, 1908. - - [162] A similar extract was sent to the Bureau of Chemistry, - and that Bureau also reported an absence of the elements of - the H_{2}S group. - - [163] Bachem, C. Pharmakologisches ueber einige Edelerden. - Arch. Internat. de Pharmacodyn., vol. 17, p. 363. 1907. - - [164] Sestini, F. Esper. di Vegetaz. del Frumento con - Sostituz. della Glucina alla Magnesia. Staz. Sper. Agrar. - Ital., vol. 20, p. 256. 1891.--Di alcuni Elementi Chimici - Rari a Trovarsi nei Vegetabili. Staz. Sper. Agrar. Ital., - vol. 15, p. 290. 1888. - - NOTE.--The ammonium sulphid precipitate was very small if the - phosphates were first removed with tin and nitric acid. - - [165] Boehm, C. R. Darstellung d. seltenen Erden, vol. 1, p. - 40. 1905. - - [166] Wait, C. E. Occurrence of Titanium. Journ. Amer. Chem. - Soc., vol. 18, p. 402. 1896. - - NOTE.--There seem to be no records of any study of the - pharmacological action of titanium. - - [167] Compare Jaksch, R. v. Ueber Mangantoxikosen und - Manganophobie. Muench. Med. Woch., p. 969. 1907. - - [168] Wohlwill, F. Ueber d. Wirkung d. Metalle d. - Nickelgruppe. Arch. f. Exper. Path., vol. 56, p. 409. 1907. - - [169] Laband, L. Zur Verbreitung des Zinkes im - Pflanzenreiche. Zeits. f. Untersuch. d. Nahrungs u. - Genussmittel, vol. 4, p. 489. 1901. - - [170] Caesium occurs in various plants and the possibility of - poisoning by this element must be considered. It is hoped - that the writer may be able to undertake a more thorough - pharmacological study of this element. - - [171] Acqua, C. Sull'accumulo di Sostanze Radioattive nei - Vegetali. Atti della Reale Accad. dei Lincei, 5 s, vol. 16, - sem. 2, p. 357. 1907. - - [172] Compare Meltzer, S. J. Toxicity of Magnesium Nitrate - When Given by Mouth. Science, vol. 26, p. 473. 1907. - - [173] Burgassi, G. Modificaz. del Ricambio per Azione dello - Stronzio. Archiv. di Farmacol., vol. 6, p. 551. 1907. - - [174] Noyes, A. A., and Bray, W. C. System of Qualitative - Analysis for the Common Elements. Journ. Amer. Chem. Soc., - vol. 29, pp. 168, 172, and 191. 1907. - - NOTE.--Barium sulphate is nontoxic on account of its - insolubility. Orfila fed 16-24 grams to dogs without causing - any disturbance. Bary, A. Beitr. z. Baryumwirkung. Dorpat, - 1888, p. 25. - - [175] Sprengel, C. Von den Substanzen der Ackerbrume und des - Untergrundes, Journ. f. Techn. u. OEkon. Chem., vol. 3, p. - 313. 1828. - - [176] Eckard, G. E. Baryt, ein Bestandtheil der Asche des - Buchenholzes. Annal. der Chem. u. Pharm., n. s., vol. 23, p. - 294. 1856. - - [177] Forchhammer, J. G. Ueber den Einfluss des Kochsalzes - auf die Bildung der Mineralien. Annal. d. Physik u. Chemie, - vol. 5, p. 91. 1905.--Lutterkorth, H. Kohlensaeurer Baryt, ein - Bestandtheil des Sandsteines in der Gegend von Goettingen. - Annal. d. Chem. u. Pharm., n. s., vol. 23, p. 296. 1856. - - [178] Dworzak, H. Baryt unter den Aschenbestandtheilen des. - AEgyptischen Weizen. Landw. Versuchs.-Stat., vol. 17, p. 398. - 1874. - - [179] Knop, W. Analysen von Nilabsatz. Landw. - Versuchs.-Stat., vol. 17, p. 65. 1874.--Compare also - Demoussy, E., Absorption par les Plantes de Quelques Sels - Solubles, These, Paris, 1899.--Knop, W., Einige neue - Resultate der Untersuchung ueber die Ernaehrung der Pflanze, - Ber. ue. Verhandl. d. koenigl. saechs. Gesells. d. Wissens. zu - Leipzig, Math. Phys. Cl., vol. 29, p. 113, 1877.--Suzuki, U., - Can Strontium and Barium Replace Calcium in Phaenogams? Bul. - Coll. Agric. Tokio Imp. Univ., vol. 4, p. 69, 1900-1902. - - [180] Hornberger, R. Ueber d. Vorkommen d. Baryums in d. - Pflanze und im Boden. Landw. Versuchs.-Stat., vol. 51, p. - 473. 1899. - - [181] Roscoe, H. E., and Schorlemmer, C. Treatise on - Chemistry, vol. 2, p. 455. 1897. - - [182] Hillebrand, W. F. Analysis of Silicate and Carbonate - Rocks. Dept. Interior, U. S. Geol. Survey, Bul. 305, p. 18. - 1907. - - [183] This report came from the Plant Analysis Laboratory of - the Bureau of Chemistry, a different one from that which - later controlled the writer's tests quantitatively and - qualitatively. In other words, the conclusions of the writer - as to the presence of barium were controlled by three - separate individuals. - - [184] Kobert, R. Kann ein in einem Pflanzenpulver gefundener - abnorm hoeher Barytgehalt erklaert werden durch direkte - Aufnahme von Baryumsalze durch die lebende Pflanze aus dem - Boden? Chem. Zeit., vol. 10, p. 491. 1899. - - NOTE.--The writer has also found barium in entirely different - botanical families from the loco-weed, and it is hoped a - report can shortly be made of some of these. - - NOTE.--The first sample of ash analyzed by the Bureau of - Chemistry had 0.21 per cent Fe_{2}O_{3}, 0.92 per cent - Al_{2}O_{3}, 0.98 per cent CaO, 0.37 per cent MgO, 5.50 per - cent SiO_{2}. The second lot was only examined for certain - constituents, and gave K_{2}O, 2.25 per cent; CaO, 1.20 per - cent; MgO, 0.41 per cent; P_{2}O_{5}, 0.52 per cent; and - SO_{3}, 0.24 per cent. - - - - -=TOTAL ASH DETERMINATIONS OF LOCO PLANTS.= - - -The reports of the ash analyses of the loco plants show marked -variations in the total amount of the ash. Thus, from _Aragallus -lamberti_ Dyrenforth obtained 4.32 per cent and O'Brine 13.52 per cent -of ash. The Bureau of Chemistry analyzed two different samples of this -dried plant and reported in one case 11.15 per cent and in the second -11.64 per cent of ash. O'Brine[185] obtained 13.52 per cent of ash from -the same species. The writer's analysis[186] gave in one sample of -_Aragallus lamberti_, collected at Hugo, Colo., in 1907, 18.8 per cent -of ash; a second lot (1907), 12.44 per cent; a third (1906), 11 per -cent, and a fourth (May, 1905) gave 37.3 per cent of ash.[187] One lot -from Woodland Park, Colo. (October, 1906), gave 6.4 per cent. One lot -from Hugo, Colo. (October, 1907), yielded 9.6 per cent. - -In the case of _Astragalus mollissimus_, Wentz obtained 6.76 per cent, -Sayre 12.01 per cent, Kennedy 20 per cent, O'Brine 12.15 per cent, while -the sample analyzed by the Bureau of Chemistry gave 18.4 per cent of -ash. One sample from Kit Carson County, Colo. (December, 1906), which -proved inactive physiologically, gave an ash content of 6.9 per cent. A -sample of _Astragalus missouriensis_ collected at Hugo, Colo., June, -1907, yielded an ash content of 21.8 per cent, and an _Astragalus -missouriensis_ collected at Pierre, S. Dak., September, 1907, yielded 27 -per cent. An _Astragalus nitidus_ from Custer, S. Dak. (July, 1907), -gave 5.2 per cent ash, while an _Astragalus nitidus_ collected at -Woodland Park, Colo., in October, 1906, yielded 7.8 per cent, and -another specimen of _Astragalus nitidus_ also collected at Woodland -Park, Colo., in October, 1907, gave 12.2 per cent. An _Astragalus -drummondii_ from Custer, S. Dak. (July, 1907), gave 5.9 per cent. -_Astragalus pectinatus_ (Hugo, June, 1907) yielded 6.1 per cent. A fresh -(undried) specimen of _Astragalus mollissimus_ (unknown origin, -November, 1907) yielded 3.8 per cent of ash. One sample of _Astragalus -decumbens_ (Ephraim, Utah, August, 1907) gave 21.8 per cent of ash. - -These determinations must necessarily be only approximate, as the plants -were collected by different persons who exercised different degrees of -care in freeing them from adherent soil, and possibly in drying the -plants, so that the main value of these figures is their aid in -determining the amount of barium present. - - * * * * * - -FOOTNOTES: - - [185] The detailed analysis of O'Brine can be found on page - 32 of this report. - - [186] All ash and barium determinations were made from the - dried plants save when otherwise specified. - - [187] Evidently these plants must have been imperfectly freed - from soil. - - - - -=BARIUM DETERMINATIONS IN THE ASH OF LOCO PLANTS.= - - -Attention has been called to the fact that in ashing plants containing -barium a part at least of this barium is converted into the insoluble -sulphate and a part into the carbonate, so that the characteristic -pharmacological action of the ash will depend not upon the total barium -present, but upon the form in which it occurs--little action if much -BaSO_{4}, and more complete if more BaCO_{3} results. A further -difficulty in the recognition of barium in plants is due to the fact -that certain inorganic salts interfere with the precipitation by -H_{2}SO_{4}. - -A specimen of _Aragallus lamberti_ (Hugo, summer of 1907) with 12.44 per -cent of ash was examined for its barium content by Hillebrand's -method.[188] The method was as follows: - -Two grams of the ash were first fused with sodium carbonate and the -fused mass washed with water containing sodium carbonate. The residue -was washed into a beaker and treated with a few drops of sulphuric acid. -The residue now remaining was filtered and after ignition was treated -with hydrofluoric and sulphuric acids. After evaporating off these -acids, the residue was treated with sulphuric acid water, filtered, and -then fused with sodium carbonate. After extracting with sodium carbonate -water, the residue was dissolved in just enough hydrochloric acid and -precipitated with sulphuric acid. The precipitate was dissolved in -concentrated sulphuric acid and reprecipitated by water and weighed as -BaSO_{4}.[189] So far as the writer can ascertain, there have been no -control experiments made for this method to determine the experimental -error. - -Of the above ash, 1.998 grams gave 5.2 milligrams of BaSO_{4}, which -would correspond to 75.75 milligrams of barium acetate crystals-- -Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O--in 200 grams of the dried plant. The -residue by the Hillebrand method after weighing was tested with the -spectroscope and gave a bright spectrum for barium. The same ash was -analyzed by the Bureau of Chemistry, using a shorter method, and they -reported 2.7 milligrams of barium sulphate in 1.1217 grams of ash. A -second sample collected earlier in the summer, with an ash content of -18.6 per cent, was shown to yield barium corresponding to 3.4 milligrams -of BaSO_{4} in 2.5 grams of the ash.[190] - -One lot of _Aragallus lamberti_ collected at Hugo, Colo., in May, 1905, -and which gave an ash content of 37.3 per cent, was found to yield 3 -milligrams of BaSO_{4} from 1.998 grams of ash, or 173.88 milligrams of -Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O in 200 grams of the dried plant, but this -ash also contained 0.27 per cent of SO_{3}. The Bureau of Chemistry -reported the barium to correspond to 2.9 milligrams of BaSO_{4} in 2.45 -grams of the ash. - -The _Astragalus missouriensis_ (Hugo, June, 1907), with an ash content -of 21.8 per cent, gave 3 milligrams of BaSO_{4} in 2.01 grams of ash, -or 76.58 milligrams of Ba(C_{2}H_{3}O_{2})_{2}+H_{2}O in 200 grams of -the dried plant. The residue after weighing was tested spectroscopically -and gave a bright barium spectrum. - -The _Astragalus drummondii_ from Custer, S. Dak. (1906), _Astragalus -mollissimus_ from Kit Carson County, Colo. (December, 1906), and -_Astragalus nitidus_ from Woodland Park, Colo. (October, 1907), were -reported by the Bureau of Chemistry to contain no barium. - -The ash of the _Astragalus pectinatus_ (Hugo, June, 1907) was reported -by the Bureau of Chemistry to show no barium on spectroscopic -examination. - -Two grams of active loco plant ash yielded from 5 to 6 milligrams of -BaSO_{4}, but it can be easily seen that in multiplying this amount to -correspond to 200 grams of the dried plant errors would be likely to -arise, so that the whole amount of barium would not necessarily be -accounted for. - - * * * * * - -FOOTNOTES: - - [188] Hillebrand, W. F. Analysis of Silicate and Carbonate - Rocks. U. S. Geol. Surv. Bul. 305, p. 116. 1907. See also - Folin, O., On the Reduction of Barium Sulphate in Ordinary - Gravimetric Determinations, in Journ. Biol. Chem., vol. 3, p. - 81. 1907. - - [189] All the determinations of barium which resulted either - positively or negatively were made with the same bottle of - sodium carbonate and H_{2}SO_{4}, so that impurities in the - chemicals were thus eliminated. - - [190] Report from Bureau of Chemistry. - - - - -=ANALYSIS OF SOILS.= - - -One sample of the soil from near Hugo, Colo., from which the _Aragallus -lamberti_ was collected, was examined by the Bureau of Soils, and that -Bureau reported the absence of barium and zirconium, at least of any -recognizable by the chemical methods used, so that it can not be said -that the barium came from any soil accidentally mixed with the ash. -Traces of titanium were, however, found. Evidently the plant must -collect minimal quantities of these elements from the soil and store -them. - -The water from a well of an adjacent area was examined by the Bureau of -Chemistry and reported to contain 37.4 parts of calcium and 13.7 parts -of magnesium in one million, and that the water contained no -barium.[191] - - * * * * * - -FOOTNOTES: - - [191] Barium has been found in well water in England. See - Thorpe, T. E., Contribution to the History of the Old Sulphur - Well, Harrogate, in Philos. Mag., 5 s., vol. 2, p. 50, 1876. - - - - -=FEEDING EXPERIMENTS WITH BARIUM SALTS ON ANIMALS IN THE LABORATORY.= - - -On these figures the writer took 0.2 gram of crystallized barium acetate -c. p., using the acetate because acetic acid has been proved in certain -loco plants by Power and Cambier, and after dissolving it in water fed -it at 9.45 a.m. to a rabbit weighing 1,177 grams. The head soon fell -forward so that the nose rested on the ground. At 10.58 a.m. the rabbit -seemed unable to guide itself and would run into obstructions if forced -to move. There was no diarrhea but it urinated several times. There was -a peculiar tremor of the muscles noted. The animal would not startle by -sudden noises and at 11.06 a.m. could be placed on its back with ease. -The pupils appeared about normal. The whites of the eyes showed very -prominently. At 11.35 a.m. the fore legs were paralyzed. The following -morning the animal was dead, its weight being 1,120 grams. The heart was -dilated; the stomach was not hemorrhagic, but rather pale. - -A second rabbit, which weighed 1,630 grams, was fed with a solution of -0.5 gram of the same salt at 9.42 a.m. At 10.35 a.m. the animal passed -soft stools and showed a marked disinclination to move, with evidence of -pain. The diarrhea[192] became more marked and the animal's hind -quarters were soiled with feces. At 10.48 a.m. there was marked -incoordination of the limbs and inability to stand. Finally, at 10.56 a. -m., convulsions began and the animal died at 11.02 a.m. The autopsy was -made about two hours later. The animal was then rigid. The kidneys -seemed rather congested. The intestines were relaxed; mesenteric vessels -dilated. The pyloric region of the stomach appeared hemorrhagic. - -A third rabbit, fed like the preceding with 0.5 gram of barium acetate, -showed much the same result. In this case there was some retching, but -the other symptoms were as above, the animal dying in one hour and five -minutes. No hemorrhages were seen in the stomach walls. It was noted -that after the administration of certain doses, 0.2 gram, there was no -diarrhea. - -On September 23, 1907, a rabbit weighing 1,757 grams was fed at 10.42 a. -m. with 0.1 gram of the same barium acetate. The temperature at the time -of feeding was 102.9 deg.F. At 12.05 a.m. the animal urinated. -Temperature, 101.4 deg.F. On September 24 the animal weighed the same. -Temperature at 10.55 a.m., 102.3 deg.F. The same amount of barium was fed. -At 3.40 p.m. the temperature was 102.5 deg.F. On September 25 the animal -weighed 1,800 grams. Temperature, 102.2 deg.F. at 10.39 a.m. The dose of -barium was repeated. At 3.55 p.m. the temperature was 101.4 deg.F. On -September 26 at 9.38 a.m. the temperature was 101.1 deg.F., and again the -barium was given. At 3.57 p.m. the temperature was 101.5 deg.F. On -September 27 the rabbit weighed 1,772 grams. The temperature at 9.53 a. -m. was 102.3 deg.F. The barium was fed for the fifth time. At 10.27 a.m. -there were general convulsions. The eyes teared. At 10.32 a.m. soft -stools appeared and the animal urinated. Stools were passed at various -periods. At 11.30 a.m. there were no signs of pain on pinching the ear. -At 11.58 a.m. the animal retched. The animal was lying with the fore -legs wide apart and could not support itself. At 12.05 p.m. the -temperature was 98 deg.F. and the rabbit died shortly after. - -The peritoneal cavity seemed normal. The small intestines were relaxed, -while the mesenteric vessels were dilated. The kidneys seemed congested. -The stomach walls were pink and in places covered with mucus. The heart -was relaxed save the left ventricle, which seemed firm. - -On September 23, 1907, a second rabbit, weighing 1,360 grams, was fed -with a similar solution and the feeding was repeated at the same time -the first rabbit was fed. On September 27 the animal weighed 1,416 -grams. On this day a peculiar movement of the hind legs on jumping -appeared, apparently due to an inability to draw the legs completely up, -and the fore legs were spread wide apart, as if too weak to support the -animal. The temperature had also fallen. On September 28 the animal had -apparently recovered. Weight, 1,516 grams on October 21. - -On September 23, 1907, a third rabbit, weighing 1,304 grams, was fed -with 50 milligrams of barium acetate. This dose was repeated each time -the other two rabbits were fed. On September 27 it weighed 1,304 grams. -Marked muscular twitching appeared, with disinclination to move. Finally -there were convulsions and paralysis of the limbs. No stools were seen. -This animal lay quiet all night, apparently unable to move, and -continued on its side until 3.15 p.m. on September 28, when it -gradually recovered, weighing 1,346 grams on October 24. - -On October 24, 1907, a rabbit weighing 1,346.5 grams was fed with a -solution of 25 milligrams of crystallized barium acetate. On the next -day the weight was 1,318 grams, and the dose was repeated. On October 26 -it weighed 1,275.7 grams, and the dose was repeated; on October 30 it -weighed 1,332 grams, and on October 31 its weight was 1,375 grams. The -animal died at night on November 6; weight, 1,134 grams. The post-mortem -examination, made with Dr. Meade Bolton, of the Bureau of Animal -Industry, was negative save for the presence of necrotic tissue in one -enlarged thyroid. - -On October 24, 1907, a rabbit weighing 1,332 grams was fed with a -solution of 25 milligrams of crystallized barium acetate. On the next -day the animal weighed the same, and the dose was repeated. On October -26 it weighed 1,289 grams, and the same amount of barium was given. On -October 28 the weight was 1,219 grams and two days later 1,289 grams. - -On October 31, 1907, a rabbit weighing 723 grams was fed with a solution -of 25 milligrams of barium acetate. This rabbit was fed in all nine -times during a period of ten days. At the end of this time it weighed -779 grams and died six days later, weighing 723 grams. The post-mortem -was negative. - -A rabbit weighing 779 grams was also fed on October 31, 1907, with a -similar amount of barium. This dose was repeated six times during an -interval of eight days. At the end of that time the animal still -retained its normal weight. On November 14, 1907, it weighed 709 grams, -having lost 70 grams. Thus after daily doses of 0.1 gram of crystallized -barium acetate no symptoms appeared until the fifth day, when death -resulted. After the similar administration of 50 milligrams severe -symptoms developed on the same day, but the animal recovered. After the -administration of 25 milligrams on three successive days the animal -died. In other cases of feeding 25 milligrams for several successive -days, some lost weight and died; others merely lost in weight, but -recovered. - -Bary fed a rabbit weighing 0.9 kilogram a solution of 30 milligrams of -barium chlorid on one day, on the second day 90 milligrams, and on the -third day 30 milligrams. The only symptom noted was diarrhea. The animal -died on the fifth day. In other words, after feeding small doses of -barium salts for several days acute symptoms suddenly set in, showing a -cumulative action. This cumulative action has been noted on man.[193] - -Onsum[194] fed a medium-sized rabbit daily with small doses of barium -carbonate, beginning with 20 milligrams. When the total amount reached -0.19 grams the rabbit died. The animal before death showed paralysis, -respiratory disturbances, and fall in temperature. The sensibility of -the cornea diminished, but the pupils responded to light. The stomach -walls showed ecchymoses and the blood vessels of the brain, the spinal -cord, and the abdominal vessels were dilated. Emboli in the pulmonary -arteries were also noted. - -In a rabbit the application of 0.66 gram of barium chlorid to a wound -was followed in twenty minutes by convulsions, paralysis, and finally -coma and death.[195] - -Of barium nitrate 0.66 gram mixed with sugar and fed to a rabbit caused -death in less than one hour, and 0.33 gram induced death in another -rabbit in twenty-seven hours.[196] - -Six grains (0.4 gram) of barium iodid fed in solution to a rabbit caused -death the following day. On this day there were tremors of the neck and -shoulders with convulsive movements of the limbs. There was also -grinding of the teeth. "The mucous membrane of the stomach was rose-red -at the cardia, and softened." Membranes of the cord and brain also were -congested.[197] - -For rabbits weighing 1,500 to 2,000 grams the lethal dose of barium -chlorid on subcutaneous use is stated to be 0.05 to 0.06 grams.[198] - -A rabbit weighing 1,106 grams was fed with a solution containing 50 -milligrams of crystallized barium acetate c. p. and 50 milligrams of -zirconium chlorid (pure). In fifty-seven minutes the animal showed -difficulty in moving the fore legs, developing marked paralysis of the -same about five hours later, and died the following morning--that is, -twenty-two hours after feeding. The heart was found dilated, kidneys -congested, stomach walls pink and covered in places with mucus and -partly digested blood, and cerebral dural vessels dilated, but no clots -were seen; bladder full. - -Mixtures of 0.5 gram of calcium acetate and 50 milligrams of barium -acetate failed to kill. Mixtures of titanium and barium were not tried, -as no titanium salt soluble in water and of neutral reaction was -accessible. - -Mittelstaedt called attention to the fact that pregnant rabbits were -more easily affected by the barium administration than nonpregnant ones, -and noted abortion in one case.[199] - -One gram of the barium carbonate killed a dog in eight hours. A second -dog died in fifteen hours. Both of these animals vomited so that a -portion of this must have been lost.[200] Barium carbonate was formerly -employed as a rat poison.[201] - -Of barium chlorid 0.6 gram, fed in aqueous solution, caused death in a -dog in forty-eight minutes if vomiting was prevented.[202] - -In Tidy's hands 2 grams of the barium nitrate caused death in a small -terrier in three and three-fourth hours. This dog had slight -convulsions, was almost unable to stand, and had vomiting and purging. -The reflexes were diminished. A small dog recovered only completely in -five days after being fed 0.66 gram, while a large dog after being fed -1.3 grams only recovered after two days. - -In cats 0.8 gram of barium carbonate when introduced into a wound caused -on the third day languor, slow respiration, feeble pulse, twitching of -hind legs, dilated pupils, and death.[203] - - * * * * * - -FOOTNOTES: - - [192] Magnus, R. Wirkungsweise u. Angriffspunkt einiger Gifte - am Katzendarm. Archiv. f. Gesam. Physiol., vol. 108, p. 44, - 1905. - - NOTE.--Reports on the histological changes in acute barium - poisoning can be found in Pilliet, A., and Malbec, A. Note - sur les Lesions Histologiques du Rein Produits par les Sels - de Baryte sur les Animaux. Comp. Rend. Hebd. Soc. de Biol., - vol. 4, p. 957. 1892. - - Literature on the pharmacology of barium not otherwise - referred to is as follows: Boehm, R. Ueber d. Wirkungen d. - Barytsalze auf d. Thierkoerper. Arch. f. Exp. Path., vol. 3, - p. 217. 1875.--Sommer, F. Beitr. z. Kennt. d. - Baryum-Vergiftung. Dissert., Wuerzburg, 1890.--Neumann, J. - Ueber den Verbleib der in den thierischen Organismus - eingefuehrten Bariumsalzen. Archiv. f. Gesam. Physiol., vol. - 36, p. 576. 1885.--Hefftner, A. Ausscheidung koerperfremder - Substanzen im Harn, Ergeb. d. Physiol., pt. 1, p. 121. - 1903.--Binet, P. Recherches Compar. sur l'Action Physiol. des - Metaux, Alcalins et Alcalino-terreux. Rev. Med. de la Suisse - Romande, vol. 12, pp. 535, 607. 1892.--Cyon, M. Ueber d. - toxisch. Wirkung. d. Baryt u. Oxalsaeureverbindungen. Archiv. - f. Anat., Physiol. u. Wissens. Med., 1866, p. 196.--Mickwitz, - L. Vergleich. Untersuch. ue. d. Physiol. Wirkung d. Salze d. - Alcalien u. Alcal. Erden. Dissert., Dorpat, 1874.--Heilborn, - F. Ueber Veraenderungen im Darme nach Vergift. mit Arsen, - Chlorbarium und Phosphor. Dissert., Wuerzburg, 1891.--Reincke, - J. J. Ein Fall mehrfacher Vergiftung durch kohlensaeuren - Baryt. Viertelj. f. gerichtl. Med., n. s., vol. 28, p. 248. - 1878.--Orfila, Memoire sur l'Empoisonnement par les Alcalis - Fixes. Journ. de Chimie Med., 2 s., vol. 8. p. 200. - 1842.--Santi, L. Se nel Veneficio per Sali di Bario questo - Metallo passa alla Urina? Gazz. Chem. Ital., vol. 33, pt. 2, - p. 202. 1903.--Weber, F. R. Barium Chloride. Milwaukee Med. - Journ., vol. 12, pp. 39, 60. 1904.--Rabuteau. De l'Innocuite - des Sels de Strontium Comparee a l'Activite du Chlorure de - Baryum. Gaz. Med. de Paris, 3 s., vol. 24, p. 218. 1869.--The - very early literature is considered in detail by Bary. - - [193] Bary, A. Beitr. z. Baryumwirkung. Dissert., Dorpat, - 1888, p. 100. - - [194] Onsum, J. Ueber d. toxisch. Wirkung. der Baryt und - Oxalsaeureverbindungen. Arch. f. Path. Anat., vol. 28, p. 234. - 1863. - - [195] Brodie, B. C. Further Experiments and Observations on - the Action of Poisons on the Animal System. Philos. Trans., - vol. 102, p. 218. 1812. - - [196] Tidy, C. M. On Poisoning by Nitrate of Baryta. Med. - Press and Circ., vol. 6, p. 448. 1868. - - [197] Glover, R. M. On the Physiological and Medicinal - Properties of Bromine and Its Compounds. Edinb. Med. & Surg. - Journ., vol. 58, p. 341. 1842. - - [198] Kissner, G. Ueber Baryum Vergiftungen u. deren Einfluss - auf d. Glykogengehalt der Leber. Scholten, 1896, p. 11. - - [199] Mittelstaedt, F. Ueber chronische Bariumvergiftung. - Dissert., Greifswald, 1895, p. 19. - - [200] Pelletier, D. Observations sur la Strontiane. Annal. de - Chimie, vol. 21, p. 119. 1797. - - [201] Christison, R. Treatise on Poisons. Edinburgh, 1845, p. - 579.--Crampe. Bewaehrte Mittel gegen Feldmaeuse. Deutsch. - Landw. Presse, vol. 5, p. 530. 1878.--Felletar, E. Faelle von - Intox. mit kohlensaeur. 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 - Toxicitaet 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. ue. 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. ue. Wirkung. u. Anwendung d. - unorganisch. Arzneistoffe. Leipzig, 1907, p. 233.--Schwilgue, - C. J. A. Traite de Mat. Med., 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 Jahrbuecher, 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 - toedlich. 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. Dodeligt forlobende 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 - Determine par l'Acetate 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 - kohlensaeurem Baryt. Arch. d. Pharm., 3 s., vol. 4, p. 426. - 1874.--Lagarde, P. Acetate de Baryte livre sous le Nom de - Sulfovinate de Soude. Union Med., 3 s., vol. 14, p. 537. - 1872.--Baum. Zwei Faelle von fahrlaessiger Toedtung durch - saltpetersaeures 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. Lecon sur l'Emploi du Muriate de Baryte - contre les Tumeurs Blanches. Gaz. Med. de Paris, 2 s., vol. - 4, p. 215. 1836. - - [219] Pauli, W., and Froehlich, 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 koerperfremder 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. Vergiftungsfaelle durch salzsaeuren Baryt - beim Rindvieh. Thieraerztl. 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 Froehner and Knudsen, Einige Versuche ueber 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 deg.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 -Luedeking[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] Luedeking, 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. - -Froehner[239] has carefully summarized the literature on the use of -barium chlorid in veterinary work, and reports that its use in the -Zuerich 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 Froehner.[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 Thieraerztl. 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] Froehner, E. Lehrb. d. Arzneimittellehre, p. 399. 1906. - Froehner gives a detailed account of these cases. - - Original note in Ehrhardt, J. Erfahrungen ue. aeltere 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 Thieraerztl. Woch., p. 16. 1899. - - [243] Froehner, E. Lehrb. d. Toxikol., 2 ed., p. 116. 1901. - - [244] Froehner, E., l. c., p. 116. - - See similar reports in Veterinarian, vol. 68, p. 572, 1895, - and vol. 69, p. 228, 1896; Zeits. f. Veterinaerk., vol. 8, pp. - 99 and 211, 1896; Nagler, F., Berliner Thieraerztl. 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. Thieraerztl. 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. Vergiftungsfaelle durch salzsaeuren - Baryt beim Rindvieh. Thieraerztl. Mittheil., vol. 5, pp. 133, - 154. 1870. - - [248] Falk. Zur Vergift. von Hunden mit Chlorbarium. Berliner - Thieraerztl. Woch., p. 40. 1897.--Schirmer, - Chlorbariumvergift. beim Hunde. Berliner Thieraerztl. Woch., - vol. 23, p. 268. 1897. - - [249] Linossier, G. De la Localisation du Baryum dans - l'Organisme a 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 - Thieraertzl. Woch., vol. 37, p. 436. 1897; Absichtliche - Vergift. mit Chlorbarium. Zeits. f. Veterinaerk., 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] Resume 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 - - Anaemia, 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 - - Boehm, 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 - - - Caesium 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 - - Froehlich, A., reference to work, 65 - - Froehner, 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 - - Luedeking, 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 - - Man, barium poisoning, 62-65 - loco poisoning, symptoms, 15 - - Manganese acetate, experiments on rabbits, 51 - - Manitoba, occurrence of loco poisoning, 10 - - Marine plants, barium taken up from sea, 53 - - Marsh, Dr. C. Dwight, investigation and collection of loco plants, - and reference to published paper, 36, 75 - - Marshall, H. T., loco plant study, reference to work, 31, 34 - - Martin, C. J., description of effects of feeding the Darling - pea to sheep, 16-17 - - Matthews, W., reference to work, 35 - - Mayo, N. S., loco-plant studies, references to work, - 11, 13, 18, 32, 71 - - Meat from locoed cattle harmless, 65 - - Medicago sativa. _See_ Alfalfa. - - Medicine, use of loco plants, 35 - - Meltzer, S. J., reference to work, 52 - - Mexico, plants causing "locoed" condition, 10, 11 - - Mickwitz, L., reference to work, 59 - - Miller, C. H., reference to work, 13 - - Mittelstaedt, F., references to work, 62, 65 - - Moffat, P., study of loco plants, 20 - - Mules, susceptibility to loco disease, 12 - - - Nagler, F., reference to work, 73 - - Nausea, effect of loco plants on man, 15, 20, 22 - - Nelson, S. B., reference to work, 33 - - Nenta, goat disease, South Africa, 17 - - Neumann, J., reference to work, 58 - - Neuritis, peripheral, in locoed animals in Australia, 17 - - New South Wales, Agricultural Gazette, references, 16, 17 - - Nightshade spp., supposed cause of locoed condition in Mexico, 10 - - Nockolds, C., references to work, 12, 14 - - Nothnagel, H., reference to work, 65 - - Noyes, A. A., reference to work, 53 - - - Oatman, H. C., experiments with alfalfa extract, 28 - - O'Brine, loco-plant studies and analyses and references to work, - 13, 18, 19, 27, 32, 33, 54 - - Onsum, J., reference to work, 61 - - Orange Judd Farmer, reference, 63 - - Orfila, reference to work, 59 - - Oserow, reference to work, 48 - - Ott, Dr. Isaac, experiments with extract of Astragalus mollissimus, - results, 22 - - Oxytropis lamberti, analyses, 20 - _See also_ Aragallus. - - - Paralysis, result of barium poisoning in man, 64 - - Parasites, loco plants, suggested cause of loco disease, 31, 34 - - Parker, W. T., reference to work, 13 - - Parkes, reference to work, 74 - - Pathological conditions in barium poisoning, 65 - locoed animals on the range, 18-19 - - Patterson, A. H., reference to work, 12 - - Pauli, W., reference to work, 65 - - Payne, J. E., reference to work, 34 - - Pelletier, D., references to work, 62, 73 - - Pigs, barium poisoning, 74 - guinea. _See_ Guinea pigs. - - Pilgrim, C. W., reference to work, 11 - - Pilliet, A., reference to work, 58 - - Plants, marine, barium taken up from sea, 53 - - Ploenius, W., reference to work, 41 - - Poison, loco, attempts to isolate the active principle, 47 - properties of certain loco plants, 35 - - Poisoning, barium, experimental, pathological lesions, 65 - horses, sheep, and pigs, 73, 74 - man, 62-65 - acute cases, symptoms, results, 64 - possibility of production from use of - food, 64 - - Poisoning, loco, theoretical antidote, 71-72 - symptoms, 11, 12-16, 17, 24, 26, 29, 33, 36-44 - reproduction in rabbits, 29, 33, 36-44, 75 - - Porcher, F. P., reference to work, 35 - - Post-mortems. _See_ Autopsies. - - Pott, E., reference to work, 35 - - Power, F. B., experiments with loco plants, 26-28 - - Pregnancy, animals in, experiments in feeding barium salts, 62 - loco plants, 41, 42 - - Prescott, A. B., study of Aragallus lamberti, 20 - - - Rabbits, autopsies after barium poisoning, 57-61, 67 - loco poisoning, 30, 34, 36-43 - barium salts, feeding experiments, 57-62 - chemicals in aqueous solutions, feeding experiments, 50-52 - loco plants, ash extracts, feeding experiments, 48-49, 66-71 - feeding experiments, 22, 24, 29, 30, 33, 34 - in laboratory, - 36-44, 48-49, 66-71 - reproduction of symptoms of loco poisoning, 29, 33, 36-44, 75 - - Rabies, treatment, use of Astragalus kentrophyta, 35 - - Rabuteau, reference to work, 59 - - Ragwort, poisonous effects, Canada, 17 - - Ram, barium poisoning, autopsy, 74 - - Ration, daily, green food for cattle, toxic effects of loco plants, 74 - - Rats, feeding experiments with barium carbonate, 71 - - Rattle-box. _See_ Crotalaria sagittalis. - - Rattleweed disease. _See_ Loco disease. - - Reichardt, E., reference to work, 64 - - Reincke, J. J., reference to work, 59 - - Resins from loco plants, experiments, 26 - - Reynolds, M. H., investigations with barium, 65 - - Rhamnus lanceolata, supposed cause of loco disease, 10 - - Rocky Mountains, high percentage of barium in rocks, 54 - - Roscoe, H. E., reference to work, 53 - - Rosenthal, D. A., reference to work, 35 - - Rossbach, M. J., reference to work, 65 - - Rothrock, description of loco plants, effects on animals, 20, 21 - - Ruedi, Carl, experiments with loco plants and references to work, - 14, 19, 29-30 - - - Sages said to cause loco disease, 11 - - Salivation, result of loco poison, 12 - use of barium on human beings, 63 - - Salt licks supposed to cause loco disease, 11 - prevention of poisonous effects of Darling pea, 17 - - Santi, L., references to work, 59, 72 - - Sayre, L. E., investigations and experiments and references to work, - 10, 11, 14, 18, 19, 22, 23, 25, 28, 29, 30, 31, 34, 48 - - Schedel, H., reference to work, 65 - - Scheibler, C., reference to work, 64 - - Schirmer, reference to work, 74 - - Schorlemmer, C., reference to work, 53 - - Schuchardt, B., description of symptoms of locoed animals, similar - to lathyrism, 15 - - Schulz, H., reference to work, 63 - - Schwartzkopff, O., references to work, 12, 13 - - Schwilgue, C. J. A., reference to work, 63 - - "Science," references to papers on loco plants, 11, 31 - - Scrofula, treatment, use of barium, 62 - - Senecio jacoboea, poisonous effects, 17 - - Sestini, F., tests for beryllium, 50 - - Sheep, autopsies after barium poisoning, 74 - loco poisoning, 18, 30, 33, 45 - disease caused by feeding on Darling pea, 16-17 - loco-plant feeding experiments, 30, 44-46 - poisoning, notes, 20, 22, 30, 33, 34 - locoed, symptoms, 14-15 - susceptibility to loco disease, 12 - - Smith, J. G., reference to work, 35 - - Snow, F. H., reference to work, 31 - - Soils, analysis, Hugo, Colo., for traces of barium, 57 - - Sophora sericea, supposed cause of loco disease, 10 - - Spine diseases, treatment, use of barium, 63 - - Sprengel, C., reference to work, 53 - - Staggers, grass, Texas loco disease, symptoms, description, 11 - - Stalker, M., description of symptoms of locoed animals and - references to work, 10, 11, 14, 15, 16, 18, 21, 26, 64 - - Steele, C. D., reference to work, 31 - - Stern, E., reference to work, 64 - - Stietenroth, reference to work, 73 - - Stipa vaseyi, supposed cause of loco disease, 10 - - Stock, losses from loco diseases, 9, 34 - poisoning by barium in brine, 73 - - Stockman, Doctor, experiments with extracts of Astragalus - mollissimus, 22 - - Storer, F. H., reference to work, 72 - - Storke, B. F., references to work, 19, 25 - - Strontium acetate, experiments on rabbits, 52 - - Subcutaneous injections. _See_ Injections. - - Sullivan, Dr. E. C., determination of barium in Aragallus lamberti, 54 - - Sulphates antidotal to barium, suggestions, 71-72, 75 - - Suzuki, U., reference to work, 53 - - Swain, R. E., reference to work, 49 - - Swainsona galegifolia. _See_ Darling pea. - spp., effects on sheep and horses, similar to loco - poisoning, 16-17 - - Syphilis, treatment, use of Astragalus exscapus, 35 - - - Taenia expansa. _See_ Tapeworm. - - Taito, F., reference to work, 64 - - Tallquist, T. W., reference to work, 31 - - Tapeworm, sheep, suggested cause of loco disease, 30 - - Texas grass staggers, loco disease, symptoms, description, 11 - - Thallium nitrate, experiments on rabbits, 50 - - Thorium chlorid, experiments on rabbits, 50 - - Thorpe, T. E., reference to work, 57 - - Tidy, C. M., reference to work, 61 - - Tiraboscht, A., reference to work, 64 - - Titanium chlorid, experiments on rabbits, 50 - - Tixier, L., reference to work, 41 - - Torrey, J., reference to work, 19 - - Toxicity, variations in extracts of loco plants, 66-71 - - Turner, F., reference to work, 17 - - - Ulcers in stomach, 18, 24, 37, 41, 43, 49, 69 - - - Vasey, George, investigations and references to work, - 12, 13, 14, 19, 20, 21 - - - Wait, C. E., reference to work, 51 - - Walsh, J., reference to work, 64 - - Watson, S., study of Aragallus lamberti, 20 - - Weber, F. R., reference to work, 59 - - Wheat, barium present, 53 - - Wheeler, G. M., references to work, 20, 21 - - Wilcox, E. V., references to work, 11, 33 - - Wilcox, T. E., reference to work, 13 - - Williams, T. A., reference to work, 10 - - Winslow, K., reference to work, 73 - - Wohlwill, F., reference to work, 51 - - Woll, F. W., reference to work, 74 - - Woolls, W., reference to work, 17 - - Worms, cause of loco disease, suggestion, 30, 31, 34 - - - Yttrium chlorid, experiments on rabbits, 51 - - - Zirconium chlorid, experiments on rabbits, 50-51 - - Zygadenus elegans, supposed cause of loco disease, 10 - - * * * * * - -TRANSCRIBER NOTES: - - Obvious typographical errors and punctuation has been - corrected without note. - - Alternate spellings and mis-spellings in the original have - been retained. - - Page 26: "analagous" changed to "analogous" (some plant - analogous to). - - Footnote 96: "Crotallaria" changed to "Crotalaria" (Poisonous - Effects of Crotalaria). - - Page 52: "Rubidum" changed to "Rubidium" (Rubidium chlorid c. - p.). - - Page 76: "is" changed to "it" (so that it is not). - - - - - -End of the Project Gutenberg EBook of Barium, A Cause of the Loco-Weed -Disease, by Albert Cornelius Crawford - -*** END OF THIS PROJECT GUTENBERG EBOOK BARIUM *** - -***** This file should be named 40256.txt or 40256.zip ***** -This and all associated files of various formats will be found in: - http://www.gutenberg.org/4/0/2/5/40256/ - -Produced by Pat McCoy, Bryan Ness and the Online Distributed -Proofreading Team at http://www.pgdp.net (This book was -produced from scanned images of public domain material -from the Google Print project.) - - -Updated editions will replace the previous one--the old editions -will be renamed. - -Creating the works from public domain print editions means that no -one owns a United States copyright in these works, so the Foundation -(and you!) can copy and distribute it in the United States without -permission and without paying copyright royalties. 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