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+*** START OF THE PROJECT GUTENBERG EBOOK 40256 ***
+
+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 Leguminosæ, 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 Süd-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 anæmia.[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 hyperæsthesia.
+
+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
+anæmia. 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 hæmocytometer.) 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, anæmia 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 anæmic. Microscopically the brain
+showed atrophy and the Purkinjie's cells disappeared or their processes
+atrophied. In these sheep the brain was so anæmic 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 anæmic.
+
+     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 portæ and the anæmia 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 hyperæsthesia 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 anæmia 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 anæmia of the brain.
+     The congestion of the vena portæ commences certainly very early,
+     but still the first symptoms are the nervous symptoms, first as
+     excitants, then depressing or sedative, with a marked hyperæsthesia
+     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 anæmia.[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 Leguminosæ.
+    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-anämie. 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. Ernährung, 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°F.; at 11.15
+a.m., 102.5°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°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°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°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°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°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°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°F.; respiration very rapid. At 2.40 p.m. the temperature was
+99.8°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 petechiæ and
+covered with mucus.
+
+_Experiment No. 7._--On February 19, 1906, a white and brown rabbit
+whose temperature was 103.2°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°F., but there
+were no marked symptoms. The following day at 2.04 p.m. the temperature
+registered 102.5°F. The same amount of extract was given at 2.09 p.m.
+The temperature at 4 p.m. was 99.8°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°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°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°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°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°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 coccideæ. 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 medullæ
+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°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°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°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°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°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°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°F.; weight 1,757.7 grams; animal
+slightly dull. February 24, temperature 102°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°F.; 3.40 p.m., no
+symptoms; 4 p.m., temperature 102°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°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°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°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 petechiæ 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°F. The temperature 1 hour and 43
+minutes later was 94.6°F., and the animal died shortly after, showing
+the same condition as occurred after feeding extracts of _Astragalus
+mollissimus_.
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [156] Compare Plönius, W., Beziehungen d. Geschwürs u. d.
+    Erosionen d. Magens z. d. funktionell. Störungen u. Krankh.
+    d. Darmes, Arch. f. Verdauungsk., vol. 13, pp. 180, 270,
+    1907, and Tixier, L., Anémies Exper. Conséc. aux Ulcér. 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 medullæ 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 methæmoglobin, but
+showed merely those of oxyhæmoglobin 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 (hydræmia), 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°F. At 1.40 p.m.
+the animal was dull; at 3.12 p.m. the temperature registered 99.8°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°F. At 11.45 a.m. this
+dose was repeated. At 12 o'clock the temperature was 104.1°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°F. The sheep had numerous soft
+stools, and was very dull, and would not eat. On June 7 the temperature
+was 103.7°F. and the sheep still refused to eat. On the 8th the
+temperature was 103.2°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°F. The sheep still did not eat,
+but had no diarrhea. It now weighed 27.9 kilos, and the temperature was
+103°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°F. On June 14 the temperature
+was 103.4°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°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°
+F. On June 20 the temperature was 102.9°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°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°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°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°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°F. At 3.42 p.m. the
+temperature was 103.5°F. At 4.20 p.m. the respiration was fairly
+rapid. On July 14, at 11.15 a.m., the temperature was 103.6°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°F. The animal had eaten. On July 17 the temperature was 104°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°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°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 Gräsern von
+    Salzgründen (Salzmooren) verursacht werden, Journ. f. Allgem.
+    Veterinär-Medicin, St. Petersburg, p. 486, 1906. Abstract in
+    Jahresber. über d. Leistungen auf dem Gebiete d.
+    Veterinär-Medicin, vol. 26, p. 226, 1906.--Compare also Étude
+    sur Quelques Plantes Vénéneuses des Regions Calcaires, Bul.
+    Soc. Cent. de Méd. Vét., 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.
+
+Cæsium 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 cæsium 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 über 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] Böhm, 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. Münch. 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] Cæsium 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. Kohlensäurer Baryt, ein
+    Bestandtheil des Sandsteines in der Gegend von Göttingen.
+    Annal. d. Chem. u. Pharm., n. s., vol. 23, p. 296. 1856.
+
+    [178] Dworzak, H. Baryt unter den Aschenbestandtheilen des.
+    Ægyptischen 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, Thése, Paris, 1899.--Knop, W., Einige neue
+    Resultate der Untersuchung über die Ernährung der Pflanze,
+    Ber. ü. Verhandl. d. königl. sächs. Gesells. d. Wissens. zu
+    Leipzig, Math. Phys. Cl., vol. 29, p. 113, 1877.--Suzuki, U.,
+    Can Strontium and Barium Replace Calcium in Phænogams? 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 höher Barytgehalt erklärt 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°F. At 12.05 a.m. the animal urinated.
+Temperature, 101.4°F. On September 24 the animal weighed the same.
+Temperature at 10.55 a.m., 102.3°F. The same amount of barium was fed.
+At 3.40 p.m. the temperature was 102.5°F. On September 25 the animal
+weighed 1,800 grams. Temperature, 102.2°F. at 10.39 a.m. The dose of
+barium was repeated. At 3.55 p.m. the temperature was 101.4°F. On
+September 26 at 9.38 a.m. the temperature was 101.1°F., and again the
+barium was given. At 3.57 p.m. the temperature was 101.5°F. On
+September 27 the rabbit weighed 1,772 grams. The temperature at 9.53 a.
+m. was 102.3°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°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. Thierkörper. Arch. f. Exp. Path., vol. 3,
+    p. 217. 1875.--Sommer, F. Beitr. z. Kennt. d.
+    Baryum-Vergiftung. Dissert., Würzburg, 1890.--Neumann, J.
+    Ueber den Verbleib der in den thierischen Organismus
+    eingeführten Bariumsalzen. Archiv. f. Gesam. Physiol., vol.
+    36, p. 576. 1885.--Hefftner, A. Ausscheidung körperfremder
+    Substanzen im Harn, Ergeb. d. Physiol., pt. 1, p. 121.
+    1903.--Binet, P. Recherches Compar. sur l'Action Physiol. des
+    Métaux, Alcalins et Alcalino-terreux. Rev. Méd. de la Suisse
+    Romande, vol. 12, pp. 535, 607. 1892.--Cyon, M. Ueber d.
+    toxisch. Wirkung. d. Baryt u. Oxalsäureverbindungen. Archiv.
+    f. Anat., Physiol. u. Wissens. Med., 1866, p. 196.--Mickwitz,
+    L. Vergleich. Untersuch. ü. d. Physiol. Wirkung d. Salze d.
+    Alcalien u. Alcal. Erden. Dissert., Dorpat, 1874.--Heilborn,
+    F. Ueber Veränderungen im Darme nach Vergift. mit Arsen,
+    Chlorbarium und Phosphor. Dissert., Würzburg, 1891.--Reincke,
+    J. J. Ein Fall mehrfacher Vergiftung durch kohlensäuren
+    Baryt. Viertelj. f. gerichtl. Med., n. s., vol. 28, p. 248.
+    1878.--Orfila, Mémoire sur l'Empoisonnement par les Alcalis
+    Fixes. Journ. de Chimie Méd., 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'Innocuité
+    des Sels de Strontium Comparée à l'Activité du Chlorure de
+    Baryum. Gaz. Méd. 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
+    Oxalsäureverbindungen. 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. Bewährte Mittel gegen Feldmäuse. Deutsch.
+    Landw. Presse, vol. 5, p. 530. 1878.--Felletar, E. Fälle von
+    Intox. mit kohlensäur. Baryum. Pest. Med.-Chir. Presse, vol.
+    28, p. 1072. 1892.
+
+    [202] Husemann, T. Ein Beitrag z. Kennt. d.
+    Barytvergiftungen. Zeits. f. pract. Heilk., vol. 3, p. 235.
+    1866. In this article Husemann has collected many cases of
+    poisoning by barium in animals.
+
+    [203] Christison, R. Treatise on Poisons. Edinburgh, 1845, p.
+    579.
+
+
+
+
+=BARIUM POISONING IN MAN.=
+
+
+The high toxicity of barium was called attention to by early observers,
+but it was attributed by some to admixed arsenic. The reports of feeding
+experiments with barium on animals have varied markedly, but now care is
+being advised in the use of barium salts.[204]
+
+Barium was introduced into medicine in the treatment of scrofula, but
+has fallen into disuse, and only recently attention has been called to
+it on account of its action on the circulatory system. Filippi,[205]
+however, says, "The effects on the heart and on the pressure are
+already the first indication of poisoning." This metal has also been
+used in the treatment of chronic diseases of the spinal cord, as
+multiple sclerosis and paralysis agitans.[206]
+
+After the administration to a woman of 1/12 grain (0.005 gram) of barium
+chlorid three to five times a day for a few days, a total of 2-1/4
+grains (0.135 gram), the patient developed rapid respiration, tenderness
+over the epigastrium, nausea, constipation, cramps in the limbs, loss of
+appetite, weakness, great emaciation, dysuria, some deafness with
+tinnitus, difficulty in speaking and thinking, with vertigo.[207] In
+this case the eyes were glassy, the vision indistinct, and the cheeks
+flushed. Kohl after the use of small doses of the same noted salivation,
+swelling of the gums, and falling out of the teeth, with a mercurial
+odor to the breath. Christison[208] states: "I have known violent
+vomiting, gripes, and diarrhea produced in like manner by a quantity not
+exceeding the usual medicinal doses." According to Kennedy few persons
+are able to bear 1/8 grain (0.0075 gram) of barium chlorid.[209]
+
+In Carpenter's case after three doses of 1.6 grains (0.070 gram) of
+barium chlorid the patient developed almost lethal symptoms.[210]
+Carpenter calls attention to the drowsiness which developed in this
+patient after the administration of barium, a fact which had already
+been noted by Christison.[211]
+
+A cartarrhal affection of various mucous membranes and a swelling of
+various glands have been noted, especially of the lymph and salivary
+glands, and in the male the testes have at times swollen.[212] The
+inflammation of the glands may pass on to suppuration. The skin becomes
+dry and shows a tendency to crack. Febrile attacks are reported after
+the repeated use of small doses of barium.
+
+Scheibler[213] has called attention to the possibility of producing
+_chronic_ barium poisoning in man from the use of barium in the
+manufacture of food products.
+
+Acute cases of poisoning in man from four or more grams of barium
+carbonate or chlorid or nitrate have been reported more or less
+frequently.[214] In the acute case of poisoning in man reported by
+Tiraboschi and Taito, no macroscopic changes were noted in the stomach
+mucosa.[215] Lopes[216] has reported one case of acute poisoning in man
+from less than 1 gram of barium chlorid. In this case paralysis of the
+limbs was a marked feature. Stern[217] cites Perondi and Lisfranc to the
+effect that "remarkably large doses of barium chlorid can be borne
+without injury by gradually increasing the doses (dissolved in much
+water)." Lisfranc[218] has suggested that the sensitiveness to poisoning
+by barium salts is greater in certain climates than in others.
+
+No data are as yet available as to the influence of altitude and partial
+starvation on the toxicity of barium salts. As is well known, almost
+all recorded cases of locoed animals have occurred at a high altitude.
+
+It must also be remembered that the addition of one salt to the solution
+of another may greatly increase the toxicity of the first one. Thus, the
+addition of a few milligrams of barium chlorid to a solution of a
+sulphocyanate renders the latter much more poisonous.[219] This may be
+due to the fact that the salts are more completely ionized.
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [204] According to v. Jaksch, "Sie ist bei der grossen
+    Toxicität der Substanz immer ernst zu stellen." Vergiftungen,
+    1897, p. 79.
+
+    NOTE.--A thorough pharmacological study of some barium salt
+    is much needed, and it is hoped that the writer will be able
+    to complete this work.
+
+    [205] Filippi, E. Modificaz. del Ricambio Organice per Azione
+    del Cloruro di Bario. La Sperimentale, vol. 60, p. 610. 1906;
+    Sull' Azione Cardiaca del Chloruro di Bario. Archivio di
+    Farmacol. Speriment., vol. 5, p. 122. 1906.
+
+    [206] Schulz, H. Vorles. ü. Wirkung. u. Anwendung d.
+    unorganisch. Arzneistoffe. Leipzig, 1907, p. 234.--Hare, H.
+    A. Use of Barium Chloride in Heart Disease. Med. News, vol.
+    54, p. 183. 1889.
+
+    [207] Ferguson, J. C. Symptoms of Poisoning from Muriate of
+    Barytes. Dublin Quart. Journ. Med. Sci., vol. 1, p. 271.
+    1846.
+
+    [208] Christison, R., l. c., p. 580.
+
+    [209] Kennedy, H. Dose of the Muriate of Barytes. Lancet,
+    vol. 2, p. 28. 1873.
+
+    [210] Carpenter, J. S. Barium Choride from a Clinical
+    Standpoint. Med. News, vol. 59, p. 93. 1891.
+
+    [211] Christison, R., l. c., 1845, p. 578.
+
+    [212] Schulz, H. Vorles. ü. Wirkung. u. Anwendung d.
+    unorganisch. Arzneistoffe. Leipzig, 1907, p. 233.--Schwilgué,
+    C. J. A. Traité de Mat. Méd., 3 ed., vol. 1, p. 441. 1818.
+
+    NOTE.--According to the files of the Office of
+    Poisonous-Plant Investigations, E. D. Smith reported in the
+    Orange Judd Farmer, 1897, that locoed animals showed a
+    swelling of various glands. As yet the writer has been unable
+    to verify this reference.
+
+    [213] Scheibler, C. Ueber d. Verwendung giftiger Stoffe,
+    besonders d. Barytverbindungen bei d. Zuckerfabrication.
+    Chem. Zeit., vol. 11, p. 1463. 1887.
+
+    [214] Schmidt's Jahrbücher, vol. 192, p. 131. 1881.--Walsh,
+    J. Report of a Case of Poisoning by Chloride of Barium.
+    Lancet, vol. 1, p. 211. 1859.--Walch. Seltener Fall einer
+    tödlich. Vergiftung d. Baryta muriatica. Zeits. f.
+    Staatsarznk., vol. 30, p. 1. 1835.--Carpenter, J. S. Barium
+    Chloride from a Clinical Standpoint. Med. News, vol. 59, p.
+    93. 1891.--Eschricht. Dødeligt forløbende Forgiftning med
+    salpetersurt Baryt. Ugeskrift for Laeger, vol. 4, p. 241.
+    1881.--Ogler and Socquet. Empoisonnement par le Chlorure de
+    Baryum. Annal. d'Hyg. Publ., 3 s., vol. 25, p. 447.
+    1891.--Chevallier, A. Note sur un Cas d'Empoisonnement
+    Déterminé par l'Acétate de Baryte. Annal. d'Hyg. Publ., 2 s.,
+    vol. 39, p. 395. 1873.--Courtin, Cas d'Empoisonnement par du
+    Chlorure de Baryum. Rev. d'Hyg., vol. 4, p. 653.
+    1882.--Poisoning by a Baryta Compound. Pharm. Journ., 3 s.,
+    vol. 2, p. 1021. 1872.--Reichardt, E. Vergiftungsfall mit
+    kohlensäurem Baryt. Arch. d. Pharm., 3 s., vol. 4, p. 426.
+    1874.--Lagarde, P. Acétate de Baryte livré sous le Nom de
+    Sulfovinate de Soude. Union Méd., 3 s., vol. 14, p. 537.
+    1872.--Baum. Zwei Fälle von fahrlässiger Tödtung durch
+    saltpetersäures Baryt. Zeits. f. Medizinalbeamte, vol. 9, p.
+    759. 1896.--Funaro, A. Sul Veneficio per Sali di Bario.
+    L'Orosi, vol. 12, p. 397. 1894.
+
+    [215] Tiraboschi, A., and Taito, F. Avvelenamento da Bario.
+    Il Risveglio Medico d'Abruzzo e Molise, vol. 1, p. 171. 1906.
+
+    NOTE.--A criticism of this case is to be found in Bellisari,
+    G., Su Di un Presunto Avvelenamento da Bario. Il Risveglio
+    Medico d'Abbruzzo e Molise, vol. 2, p. 15. 1907.
+
+    [216] Lopes, A. Caso Curioso de Envenenamento Pelo Chloret de
+    Bario. Medicina Contempt., Lisbon, vol. 4, p. 109. 1886.
+
+    [217] Stern, E. Vergiftung mit Chlorbarium. Zeits. f.
+    Medizinalbeamte, vol. 9, p. 383. 1896.
+
+    NOTE.--The writer has always theoretically questioned the
+    danger of poisoning by loco weeds in well-fed and
+    well-watered animals. Compare Stalker, M., The "Loco" Plant
+    and Its Effect on Animals. Bur. Animal Industry, 3d Ann.
+    Report (1886), p. 271. 1887.
+
+    [218] Lisfranc. Leçon sur l'Emploi du Muriate de Baryte
+    contre les Tumeurs Blanches. Gaz. Méd. de Paris, 2 s., vol.
+    4, p. 215. 1836.
+
+    [219] Pauli, W., and Fröhlich, A. Pharmakodynam. Studien.
+    Sitz. Kaiserl. Acad. d. Wissens. z. Wien, vol. 115, III, pt.
+    6, p. 445. 1906.
+
+
+
+
+=PATHOLOGICAL LESIONS IN EXPERIMENTAL BARIUM POISONING.=
+
+
+The post-mortem examinations in cases of acute experimental barium
+poisoning, according to Schedel,[220] show punctiform or large
+hemorrhagic effusion in the fundus ventriculi[221] and in the large and
+small intestines, contraction of the bladder, and hemorrhage into the
+walls of the bladder and uterus. The heart is usually found relaxed or
+the left ventricle contracted in systole, while the right is relaxed.
+Only once were ecchymoses under the endocardium seen. The liver and
+kidneys showed nothing special. The urine was free from albumen and
+sugar. In a few cases the lungs showed some infiltration with blood. In
+chronic cases, according to our own investigations in rabbits, there are
+no characteristic macroscopic lesions, a result which agrees with
+Mittelstaedt's report.[222] Nothnagel and Rossbach[223] claim that in
+chronic poisoning by barium the peripheral nerves are altered. The same
+negative results have also been reported in chronic poisoning in higher
+animals. Reynolds[224] noted a layer like a blood clot under the
+cerebellum in a horse fed with barium chlorid. Fuchs[225] has called
+attention to the fact that the flesh of cattle poisoned with barium
+chlorid was harmless, perhaps owing to a conversion into an insoluble
+salt, a fact which may be considered in the use of locoed animals for
+food.
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [220] Schedel, H. Beitr. z. Kennt. d. Wirkung des
+    Chlorbariums. 1903, p. 13.
+
+    [221] After subcutaneous injection of barium chlorid, Lewin,
+    by means of the spectroscope, has found barium in the stomach
+    walls. Lewin, L. Schicksal körperfremder chem. Stoffe im
+    Menschen u. besonders ihre Ausscheidung. Deutsch. Med. Woch.,
+    vol. 32, p. 173. 1906.
+
+    [222] Mittelstaedt, F. Ueber chronische Bariumvergiftung.
+    Dissert., Greifswald, 1895, p. 29.
+
+    [223] Nothnagel, H., and Rossbach, M. J. Handb. d.
+    Arzneimittel, p. 81. 1904.
+
+    [224] Reynolds, M. H. A Study of Certain Cathartics. Minn.
+    Agric. Exper. Sta., 15th Ann. Rept. 1907.
+
+    [225] Fuchs, C. J. Vergiftungsfälle durch salzsäuren Baryt
+    beim Rindvieh. Thierärztl. Mittheil., vol. 5, p. 159. 1870.
+    Fuchs suggests that further investigations on this point are
+    desirable. The literature of this class of experiments is
+    very scanty. See Fröhner and Knudsen, Einige Versuche über d.
+    Geniessbarkeit d. Fleisches vergift. Thiere. Monats. f.
+    Prakt. Thierheilk., vol. 1, p. 529. 1890.
+
+
+
+
+=TOXICITY OF VARIOUS AQUEOUS EXTRACTS OF LOCO PLANTS.=
+
+
+On October 21, 1907, a rabbit weighing 1,531 grams was fed with an
+extract of 95 grams of dried _Aragallus lamberti_ (Hugo, Colo., 1907),
+with an ash content of 12.44 per cent, with a barium content estimated
+as 2.6 milligrams of BaSO_{4} in 1 gram of ash. On the following day it
+weighed 1,517 grams, and the same dose was again administered. On
+October 23 the weight was 1,488 grams, and the dose was repeated. On the
+next day the weight was the same and the dose was repeated. On October
+26 the weight was 1,446 grams, and again the same extract was given. On
+October 30 the animal weighed 1,502.5 grams; on October 31, 1,531 grams.
+The animal received a total extract of 475 grams of the dried plant
+without serious injury. This result was apparently contradictory to the
+earlier work.
+
+On October 21, 1907, a rabbit weighing 1,743 grams was fed with an
+extract of 47.5 grams of the same dried plant. On the next day its
+weight was 1,729 grams, and the same amount of the extract was fed. On
+October 23 the weight remained the same, and the dose was repeated. On
+October 24 the weight was 1,658 grams, and the same amount of extract
+was fed. On October 26 the animal weighed 1,630 grams, when it was again
+fed with the same amount of extract. On October 28 the animal weighed
+1,573.5 grams, but two days later the weight had risen to 1,644 grams.
+An extract of 237.5 grams had been administered. Here again the results
+appeared contradictory.
+
+On October 21, 1907, a rabbit weighing 1,517 grams was fed with an
+extract of 77.5 grams. On the next day it weighed 1,545 grams, and the
+dose was repeated. On October 23 the animal weighed 1,531 grams, and the
+same amount of extract was given. On the following day it weighed 1,488
+grams, and the dose was repeated. On October 26 it weighed 1,474 grams,
+and again the dose was repeated. On October 30 the weight had risen to
+1,545 grams, and on October 31 it was 1,559 grams. This animal received
+in all an extract of 387.5 grams of the dried plant. An aqueous extract
+of 200 grams of the same in one dose also failed to produce the acute
+symptoms.
+
+These feeding experiments show little of the characteristic action seen
+in the earlier experiments made with aqueous extracts either of the dry
+plant or of the fresh plant preserved with chloroform. In other words,
+the aqueous extract of the dried plant was only slightly poisonous, yet
+the plant from which the extract was made contained barium.
+
+Of this same dried loco 200 grams were then extracted with water and
+digested with pepsin and finally with pancreatin in the thermostat
+(37.5°C.). The extract was concentrated and fed to a rabbit weighing
+1,616 grams. After five hours and ten minutes the animal appeared weak
+in the fore legs and unable to support himself, and he died during the
+night. The intestines the following morning were found full of gas, the
+stomach red, the lungs seemed normal, and the heart was relaxed.
+
+A rabbit weighing 1,545 grams was fed on November 15, 1907, with a
+preparation made in a similar manner, save that the plant was not
+extracted with water before digestion. On the next day it weighed 1,517
+grams and on November 19, 1,361 grams. The following day the weight was
+1,318 grams; on November 21, 1,233 grams, and on the next day 1,162
+grams. The animal died during the night, and the autopsy was made the
+following morning.
+
+The animal was greatly emaciated and the subcutaneous fat had almost all
+disappeared. The mesenteric vessels were dilated, but the intestines
+were not dilated. The peritoneal cavity was normal. The kidneys were
+perhaps a little injected, and measured 3 cm. in length. The lungs were
+normal. The left ventricle was contracted and the rest of the heart
+relaxed. The liver was normal and the spleen apparently normal. The
+stomach walls were dark, owing to decomposition. No ulcers were seen.
+The suprarenals were perhaps a little enlarged. The examination of the
+brain was negative, and no clots were found.
+
+A similar digestion from 200 grams of the same dried plant was then
+ashed and the ash treated with acetic acid and freed from acid by
+evaporation on the bath. The ash which was insoluble in water was ground
+up into a fine paste and the whole was fed to a rabbit weighing 992
+grams. This animal died in forty minutes, showing the characteristic
+symptoms seen in acute cases already described. In the autopsy the lungs
+and other organs seemed perfectly normal macroscopically. The stomach
+walls, however, were reddened and ecchymotic, and the mesenteric vessels
+were dilated.
+
+On January 8, 1908, a similar digestion of the same batch was treated
+with a few drops of sulphuric acid to remove the barium, and the
+filtrate was then treated with lead carbonate to remove the sulphuric
+acid. After careful filtering, H_{2}S was passed into the solution and
+after concentration was fed in one dose on January 9, 1908, to a rabbit.
+The following morning the rabbit had gained in weight. On January 14
+this animal weighed 30 grams more than its initial weight.
+
+The residue of this plant after such a digestion, examined by the
+Hillebrand method, showed no weighable amount of barium, so that it can
+be seen that barium in relatively large amount was found in the plant
+itself, but not after the digestion. It must therefore have been the
+aqueous digestion which produced the characteristic symptoms. The
+examination of this fluid for barium might, however, be misleading, as
+the large amount of proteids would unquestionably interfere with the
+determination of this amount of barium, unprotected by other salts and
+silica, so that this side of the investigation was not pursued. Control
+feedings with an emulsion of one-half gram each of pepsin and pancreatin
+proved inactive.
+
+Of the same _Aragallus lamberti_ 200 grams were similarly digested and
+the barium was removed with a few drops of H_{2}SO_{4}, the sulphuric
+acid by PbCO_{3} and a little lead acetate, and the lead by H_{2}S. Such
+an extract it was shown in the previous experiment would not kill.
+However, to this extract was added 100 milligrams of crystallized barium
+acetate in a solution and a precipitate formed. Nevertheless, the liquid
+and the precipitate were fed on February 1, 1908, to a rabbit weighing
+1,304 grams. On February 3 the animal weighed 1,233 grams; on February
+4, 1,176 grams; February 5, 1,120 grams; February 6, 1,006 grams;
+February 7, 1,219 grams; February 8, 1,219 grams; February 10, 1,304
+grams.
+
+As a control for this animal, to make sure that the loss in weight was
+not due to the acetic acid set free by the treatment with H_{2}S, a
+similar aqueous extract of the same lot of _Aragallus lamberti_ was
+precipitated with very much more lead acetate than in the preceding
+cases and also with lead subacetate and then H_{2}S. After evaporating
+to dryness this was fed on February 8, 1908, to a rabbit weighing 1,035
+grams. On February 11 it weighed 1,021 grams; on February 13, 1,091
+grams, and on February 15, 1,120 grams, showing a gain in weight.
+
+Of the dried _Astragalus missouriensis_ (Hugo, Colo., June, 1907) 400
+grams with an ash content of 21.8 per cent and which was known to
+contain barium (3 mg. BaSO_{4} in each 2 grams of the ash) were
+extracted with water and fed in four doses corresponding to 100 grams
+each in a period of four days. On November 18, 1907, the first day of
+feeding, this rabbit weighed 1,856.7 grams. Fifteen days later it
+weighed 1,984.3 grams.
+
+One hundred grams of this dried plant after extraction with water were
+found to leave about 51.1 grams[226] of the plant undissolved. This when
+ashed yielded 8.2 grams of ash. Two grams of this ash yielded 5
+milligrams of BaSO_{4}. In other words, the aqueous extract of the plant
+was inactive and the barium was found practically unextracted in the
+residue of the plant.
+
+Evidently the barium in these dried plants had been converted into an
+insoluble form by drying or by some peculiarity of its metabolism, and
+was not extracted by water, but could be extracted by digesting the
+plants with the combined digestive ferments, pepsin and pancreatin.
+
+Of the same dried _Astragalus missouriensis_ 200 grams were extracted
+with water and the extract treated with lead carbonate to remove any
+possible free sulphates and after filtering this was treated with H_{2}S
+to remove the lead. As the preceding experiment showed that the aqueous
+extract of this dried plant was harmless without barium, the writer
+decided to add barium artificially, and 100 milligrams of barium
+phosphate,[227] crystallized, was added to the liquid and the whole fed
+to a rabbit weighing 2,423.9 grams. The following morning the rabbit was
+found dead. The autopsy was made by Dr. H. J. Washburn, of the Bureau of
+Animal Industry. He found that the suprarenals were enlarged and
+congested, and there were small areas of hepatization at the apex of
+each lung. There were also acute corrosion areas on the greater
+curvature of the stomach and over the upper portion of the duodenum.
+
+Of the _Astragalus missouriensis_ used in the preceding experiments, 200
+grams were extracted thoroughly with water, and the extract
+corresponding to 100 grams, together with 80 milligrams of barium
+phosphate pure, was fed on March 12, 1908, to a rabbit weighing 1,261.5
+grams. During this day the animal walked at times with an uncertain gait
+and the following morning it weighed 1,233 grams. It was then fed the
+rest of the solution, that is, the extract of the remaining 100 grams of
+the plant, but without any barium. The animal soon developed convulsions
+and died in a little over twenty-four hours after the original feeding.
+The autopsy, which was made by Dr. J. R. Mohler, of the Bureau of Animal
+Industry, showed that the mucous membrane of the stomach was markedly
+hemorrhagic and in areas gelatinous infiltration was very marked. In one
+portion of this hemorrhagic area there was distinct erosion. The large
+intestines were full of gas, the lungs were normal, the heart was
+relaxed, and the lungs collapsed. The blood vessels of the kidneys were
+markedly engorged.
+
+Of the dried _Astragalus nitidus_ (Woodland Park, Colo., October, 1907)
+which was reported by the Bureau of Chemistry as containing no barium,
+200 grams were extracted with water and fed in 100-gram doses for two
+successive days. The animal increased steadily in weight and fifteen
+days after the first feeding had gained 99.2 grams. This amount of the
+plant was also extracted with water and the residue was then digested
+with pepsin and pancreatin in the thermostat, as in the previous case,
+and fed in two doses corresponding to 100 grams each. This animal
+increased in weight, gaining 60 grams in six days and 165 grams in
+addition after a further fifteen days.
+
+An _Astragalus mollissimus_ (Kit Carson County, Colo., December, 1906),
+which was also reported by the Bureau of Chemistry as containing no
+barium, was extracted with water, and a dose corresponding to an extract
+of 200 grams of the dried plant was fed in one dose without any serious
+result. The same amount of the dried plant was also similarly digested
+with pepsin and pancreatin and fed in two doses, but without the
+production of any symptoms, the rabbit gaining 60 grams in four days.
+
+Of the _Aragallus lamberti_ (Hugo, Colo., June, 1907), with an ash
+content of 12.44 per cent, 250 grams were ashed and the ash treated with
+acetic acid and, after evaporating off the acetic acid, was extracted
+with water and the ash digested with pepsin and pancreatin. The aqueous
+extract and the digestion products of the ash were then fed after
+concentration, but without any serious effects to the animal, indicating
+that in this plant the barium is in a form insoluble in water and in the
+ashing is further changed so that it can not now be made soluble by
+digestion--an opposite result to the experiment in which the barium was
+first rendered soluble by digestion and the digestion products ashed,
+suggesting a possibility that plants might be found in which the barium
+is not extracted by digestion, at present a hypothesis.
+
+Of dried _Astragalus decumbens_ (Ephraim, Utah, 1907), which was
+reported by the Bureau of Chemistry to contain no barium, 200 grams also
+failed to produce symptoms in rabbits by our test.
+
+A solution containing 50 milligrams of barium acetate (crystallized) was
+mixed with an aqueous extract of 200 grams of the dried _Aragallus
+lamberti_ which had proved inactive pharmacologically, but a precipitate
+formed (BaSO_{4}?) and the extract still remained inactive, suggesting
+that the question of toxicity depended not only upon the presence of
+barium, but also whether other agents, such as sulphates, etc., might
+not be present in sufficient amount to render the barium insoluble; that
+is, pharmacologically inactive.
+
+This _Aragallus lamberti_ yielded an ash content of 37.3 per cent, and
+the SO_{3} group was estimated at 0.27 per cent of the ash, while a
+corresponding lot which was obtained two years later from the same area
+yielded an ash content of 12.44 per cent and a SO_{3} content of 0.24
+per cent of the ash.
+
+It may be urged that the full lethal dose of the barium was not always
+found in the plant, yet it must be remembered that the toxic action was
+the resultant of the action of the total constituents and that if the
+barium was removed the extract was practically harmless.
+
+In looking back over the work the most suitable preparation for
+producing the characteristic symptoms in rabbits seems to be the freshly
+ground-up plant mixed with water and preserved in chloroform, for while
+the dried plant might contain barium, yet the aqueous extract was often
+inactive, suggesting, perhaps, the presence of something in the fresh
+plant which aided the solution of the barium, thus accounting for the
+variations in toxicity of aqueous extracts made from plants dried under
+varying conditions. The nature of the compound in which barium exists in
+the plant is as yet unknown and has not been investigated. _It is
+important to remember that not only must barium be found in the plant to
+prove poisonous, but it must be in such a form that it can be extracted
+in the gastro-intestinal canal._
+
+The amount of barium found in various species of loco plants will no
+doubt vary, and perhaps the pharmacological test on rabbits as the
+writer has used it may have to be modified for such plants, so that at
+present the wisest plan to test these plants is to determine their
+barium content and also make the physiological test, as has been
+proposed, and if the barium content runs low, say below 0.11 per cent of
+the ash, in plants yielding from 12 to 18 per cent of ash, then to
+increase the number of feedings on the rabbit. No doubt on ranges where
+a large number of loco plants are eaten, with little other food, plants
+with a very low barium content may be poisonous, but if large amounts of
+other food are fed the writer would expect few, if any, serious results.
+
+As the writer's work has been confined to the laboratory side of the
+loco-weed investigations no feeding experiments with barium salts have
+been made by him on large animals. Such experiments should, of course,
+be made under range conditions; that is, where the water and food supply
+is deficient.
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [226] Some was lost, being attached to the cloth used in
+    squeezing the extract.
+
+    [227] This barium phosphate was determined by the Bureau of
+    Chemistry to be BaHPO_{4} and to contain traces of iron,
+    sodium, and potassium, but it was free from arsenic.
+
+
+
+
+=THEORETICAL ANTIDOTE FOR LOCO-WEED POISONING.=
+
+
+The fact that treatment of the loco-weed extract with a few drops of
+sulphuric acid, which will remove the barium, renders these extracts
+harmless, and even apparently nutritious, would suggest the theoretical
+antidotal treatment to be with sulphates, in the form, perhaps, of epsom
+salts, but perhaps alkaline bicarbonates may be present in the stomach,
+either due to lessened acidity of the stomach or from drinking alkaline
+waters, in which case the precipitation of the barium by sulphates would
+presumably be interfered with, and thus the treatment be rendered
+ineffectual.[228] It is interesting to note that most of the remedies
+proposed for the successful treatment of locoed animals contain
+sulphates.[229]
+
+In Storer's experiments on feeding rats with barium carbonate it was
+found that the barium carbonate would kill them, but if calcium
+carbonate was mixed with the barium the rats survived, suggesting an
+antidotal action. This apparent antagonism deserves further study and
+may lead to practical results.[230] A somewhat similar antagonism for at
+least a part of the action of barium has been claimed to exist between
+barium and potassium.[231] However, extracts of ashed plants, treated
+with acetic acid, which contained calcium and potassium, caused death in
+the experiments of the writer, but no work has yet been done by him as
+to the antidotal action of calcium carbonate on barium. Then, too, as
+Lüdeking[232] pointed out, large quantities of calcium chlorid may
+interfere with the precipitation of barium as a sulphate. It is well
+known that the presence of various salts influences the solubility of
+barium sulphate in water,[233] and the fact that barium has been found
+in solution in the urine in the presence of sulphates shows that the
+precipitation of barium as a sulphate in the body is not so simple as in
+test-tube experiments.[234] Again, in very dilute solutions, such as
+must necessarily occur at any one time in the stomach, the precipitate
+with sulphates only slowly forms and the barium may be absorbed before
+the insoluble compound can be formed.[235] Evidently an important point
+to be considered in the antidotal treatment of locoed animals with
+sulphates is the possibility of inducing a gastritis, with its attendant
+loss of weight. It therefore seems apparent that the proper treatment at
+present is preventive--that is, removal from the plants.
+
+Lewin[236] has suggested the possibility of acquiring some immunity to
+barium, but our experiments point against the production of any
+practical immunity.
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [228] Mendel, L. B., and Sicher, D. F., l. c., p. 148.
+
+    [229] Mayo, N. S. Some Observations upon Loco. Kans. State
+    Agric. Coll. Bul. 35, p. 119. 1893.
+
+    [230] Storer, F. H. Experiments on Feeding Mice with
+    Painter's Putty and with Other Mixtures of Pigments and Oils.
+    Bul. of Bussey Institute, vol. 2, p. 274. 1884.
+
+    [231] Brunton, T. L., and Cash, J. T. Contribution to Our
+    Knowledge of the Connection between Chemical Constitution,
+    Physiological Action, and Antagonism. Philos. Trans. Royal
+    Soc. London, I, vol. 175, p. 229. 1884.
+
+    [232] Lüdeking, C. Analyse d. Barytgruppe. Zeits. f. Anal.
+    Chem., vol. 29, p. 556. 1890.
+
+    [233] Fraps, G. S. Solubility of Barium Sulphate in Ferric
+    Chloride, Aluminum Chloride, and Magnesium Chloride. Amer.
+    Chem. Journ., vol. 27, p. 288. 1902.
+
+    [234] Santi has paid special attention to the solubility of
+    barium in the body.
+
+    [235] Fresenius, C. G. Man. of Qualitat. Chem. Anal. Tr. by
+    H. L. Wells, 1904, p. 148.
+
+    [236] Lewin, L. Nebenwirkungen d. Arzneimittel, 2 ed., p.
+    439. 1893.
+
+
+
+
+=ACTION OF BARIUM ON DOMESTIC AND FARM ANIMALS.=
+
+
+Barium in the form of barium chlorid has been recently introduced into
+veterinary therapeutics by Dieckerhoff[237] in the treatment of
+constipation, but Winslow[238] says that "the doses required to produce
+catharsis in the horse are almost toxic," and he advises against the
+intravenous use of this remedy.
+
+Fröhner[239] has carefully summarized the literature on the use of
+barium chlorid in veterinary work, and reports that its use in the
+Zürich clinic has recently been so unsatisfactory that it is now seldom
+employed and that in the last ten years the preponderance of reports in
+the literature are unfavorable to the use of this agent in colic.
+
+After the administration per os, much of the barium must be carried off
+in the diarrheal stools. A number of deaths in horses have been
+attributed to the use of this agent. No doubt the presence of sulphates,
+etc., derived from the food would render the barium insoluble in the
+gastro-intestinal tract, and this would explain the lack of poisonous
+action in certain of the cases in which large doses of barium proved
+harmless.
+
+Husard and Biron administered daily doses of 8 grams of barium chlorid
+to one horse, and the same amount of barium carbonate to a second horse,
+for several days. A fortnight later the first horse unexpectedly died,
+and the second a few days later. The post-mortem examination was
+negative.[240] A third horse fed with barium carbonate also died
+suddenly. Recently barium occurring in brine has given rise to acute
+poisoning in stock.[241]
+
+In a case reported by Stietenroth[242] the horse died after the
+injection of 0.5 gram of barium chlorid into the jugular vein. A number
+of sudden deaths in horses after the intravenous injection of 0.7 gram
+and over of barium chlorid have been collected by Fröhner.[243] The
+lethal dose by mouth for acute poisoning with barium chlorid in horses
+lies between 8 to 12 grams, while cattle require much larger doses (40
+grams)[244] to induce death.
+
+Dieckerhoff advises against the use of barium chlorid in the treatment
+of constipation in sheep.
+
+After a dose of 6 grams of barium chlorid a 2-year-old healthy ram
+appeared perfectly well, but the following day he was depressed, refused
+to eat, staggered, and became so weak that he was unable to stand. The
+muscles of the extremities were paralyzed and the animal died. "The
+post-mortem examination revealed oedema of the lungs, slight
+cloudiness of the heart muscles, numerous small hemorrhagic spots on the
+mucous membrane of the small intestine, and stagnation of the blood in
+the vessels of the small and large intestines. Similar symptoms and
+lesions were found in a lamb 4 months old which was given per os 6.0
+grams of barium chlorid dissolved in 200 grams of distilled water."[245]
+
+Poisonings with barium carbonate have also been reported in pigs.[246]
+Domestic animals pastured in the neighborhood of barite deposits soon
+succumb,[247] and accidental cases of poisoning are reported in cows.
+Poisoning in dogs has also been reported after the subcutaneous use of
+this agent.[248] Linossier says that if the barium salts are used for
+any time the salts are deposited in various organs, largely in the
+kidneys, brain, and medulla, but especially in the bones.[249]
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [237] Dieckerhoff. Ueber d. Wirkung d. Chlorbaryum bei
+    Pferden, Rindern und Schafen. Berliner Thierärztl. Woch., p.
+    265; see also pp. 313 and 337, 1895; Abstract In Vet. Mag.,
+    vol. 2, p. 360. 1895.
+
+    [238] Winslow, K. Vet. Materia Medica and Therapeutics, p.
+    152. 1901.
+
+    [239] Fröhner, E. Lehrb. d. Arzneimittellehre, p. 399. 1906.
+    Fröhner gives a detailed account of these cases.
+
+    Original note in Ehrhardt, J. Erfahrungen ü. ältere u. neue
+    Arzneimittel. Schweizer Archiv. f. Thierheilk., vol. 41, p.
+    44. 1899.
+
+    [240] Pelletier. Observations on Strontian. Journ. Nat.
+    Philos., vol. 1, p. 529. 1797; original in Annales de Chimie,
+    vol. 21, p. 127. 1797.
+
+    [241] Howard, C. D. Occurrence of Barium in the Ohio Valley
+    Brines and Its Relation to Stock Poisoning. W. Va. Univ.
+    Agric. Exper. Sta. Bul. 103. 1906.
+
+    [242] Stietenroth. Ueber Chlorbarium bei der Kolik der
+    Pferde. Berliner Thierärztl. Woch., p. 16. 1899.
+
+    [243] Fröhner, E. Lehrb. d. Toxikol., 2 ed., p. 116. 1901.
+
+    [244] Fröhner, E., l. c., p. 116.
+
+    See similar reports in Veterinarian, vol. 68, p. 572, 1895,
+    and vol. 69, p. 228, 1896; Zeits. f. Veterinärk., vol. 8, pp.
+    99 and 211, 1896; Nagler, F., Berliner Thierärztl. Woch., p.
+    65. 1896.
+
+    [245] Dieckerhoff, W. Vet. Mag., vol. 2, p. 362. 1895.
+
+    [246] Kabitz, H. Ueber d. Wirkung einiger Baryumsalze beim
+    Schwein. Deutsch. Thierärztl. Woch., vol. 13, p. 317. 1905.
+
+    [247] Parkes. Chem. Essays, vol. 2, p. 213. Quoted by
+    Christison, R., in Treatise on Poisons, Edinburgh, 4 ed., p.
+    581, 1845.--Fuchs, C. J. Vergiftungsfälle durch salzsäuren
+    Baryt beim Rindvieh. Thierärztl. Mittheil., vol. 5, pp. 133,
+    154. 1870.
+
+    [248] Falk. Zur Vergift. von Hunden mit Chlorbarium. Berliner
+    Thierärztl. Woch., p. 40. 1897.--Schirmer,
+    Chlorbariumvergift. beim Hunde. Berliner Thierärztl. Woch.,
+    vol. 23, p. 268. 1897.
+
+    [249] Linossier, G. De la Localisation du Baryum dans
+    l'Organisme à la Suite de l'Intoxication Chronique par un Sel
+    de Baryum. Comp. Rend. Hebd. Soc. de Biol., 8 s., vol. 4, p.
+    123. 1887.
+
+    NOTE.--Other cases of poisoning in animals may be found in
+    Marder, Beitrag z. Giftwirkung des Baryum chloratum. Berliner
+    Thierärtzl. Woch., vol. 37, p. 436. 1897; Absichtliche
+    Vergift. mit Chlorbarium. Zeits. f. Veterinärk., vol. 9. p.
+    72. 1897.
+
+
+
+
+=APPLICATION OF THE RESULTS OF THESE INVESTIGATIONS TO THE RANGE.=
+
+
+It has been calculated that a medium estimate of food for cattle on
+green fodder is about 60 pounds (30 kilos) a day.[250] Calculating this
+entirely in terms of _Aragallus lamberti_ and allowing 10 per cent of
+moisture for these plants (Sayre) would make 27 kilos of dry loco eaten
+by each animal per diem. In the analysis of the writer of one _Aragallus
+lamberti_ from Hugo, Colo., it was found to yield 12.44 per cent of ash,
+and the barium content corresponded to 2.6 milligrams BaSO_{4} in each
+gram of the ash. This would correspond to 10.24 grams of barium acetate
+(Ba(C_{2}H_{3}O_{2})_{2} + H_{2}O) or 9.15 grams of barium chlorid
+(BaCl_{2} + 2H_{2}O) per diem. This amount daily administered would,
+theoretically, readily produce chronic poisoning owing to the
+accumulation in the system, as was shown in the case of rabbits.
+
+There is, however, some question as to whether this full theoretical
+amount of loco plants is eaten on the range, and the estimate has been
+made that one-sixth of this amount only would be actually taken. It must
+be remembered, as Stalker pointed out, that locoed animals develop an
+especial taste for these plants and after a time reject other food, so
+that while the number of loco plants at first taken may be small, yet
+later, perhaps, it is greater. A part of this barium, however, may not
+be taken up by the system, but may pass out undissolved. No actual
+experiments have yet been made with cattle by feeding small doses of the
+pure salt.
+
+No doubt more of the pure barium salts will be required to produce
+symptoms of poisoning in animals than would be necessary in the case of
+the form of barium found in the plant, as in the loco-weed the barium is
+probably better protected from precipitation than are the barium salts
+when dissolved in water alone.
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [250] Lane, C. B. Soiling Crop Experiments. N. J. Agric.
+    Exper. Sta. Bul. 158, p. 18. 1902.--Woll, F. W. One Hundred
+    American Rations for Dairy Cows. Univ. Wis. Agric. Exper.
+    Sta. Bul. 38, p. 12. 1894.--N. J. State Agric. Exper. Sta.,
+    20th Ann. Rept. (1899), p. 193. 1900.
+
+
+
+
+CONCLUSIONS.[251]
+
+
+(1) Conditions analogous to those met with in locoed animals occur in
+other portions of the world, especially Australia.
+
+(2) The main symptoms described in stock on the range can be reproduced
+on rabbits by feeding extracts of certain loco plants. Those especially
+referred to here under the term "loco plants" are _Astragalus
+mollissimus_ and _Aragallus lamberti_.
+
+(3) The production of chronic symptoms in rabbits is a crucial test of
+the pharmacological activity of these plants.
+
+(4) The inorganic constituents, especially barium, are responsible for
+this action, at least in the plants collected at Hugo, Colo. Perhaps in
+other portions of the country other poisonous principles may be found.
+
+(5) A close analogy exists between the clinical symptoms and
+pathological findings in barium poisoning and those resulting from
+feeding extracts of certain loco plants. Small doses of barium salts may
+be administered to rabbits without apparent effect, but suddenly acute
+symptoms set in analogous to what is reported on the range.
+
+(6) The administration of sulphates, especially epsom salts, to form
+insoluble barium sulphate would be the chemical antidote which would
+logically be inferred from the laboratory work, but of necessity this
+would have to be frequently administered and its value after
+histological changes in the organs have occurred remains to be settled.
+But even the treatment of acute cases of barium poisoning in man is not
+always successful, even when sulphates combined with symptomatic
+treatment are employed. The conditions under which the sulphates fail to
+precipitate barium must be considered. At present it seems best to rely
+on preventive measures rather than on antidotal treatment.
+
+(7) Loco plants grown on certain soils are inactive pharmacologically
+and contain no barium. In drying certain loco plants the barium
+apparently is rendered insoluble so that it is not extracted by water,
+but can usually be extracted by digestion with the digestive ferments.
+
+(8) The barium to be harmful must be in such a form as to be dissolved
+out by digestion.
+
+(9) In deciding whether plants are poisonous it is desirable not merely
+to test the aqueous or alcoholic extract, but also the extracts obtained
+by digesting these plants with the ferments which occur in the
+gastro-intestinal tract.
+
+(10) It is important that the ash of plants, especially those grown on
+uncultivated soil, as on our unirrigated plains, be examined for various
+metals, using methods similar to those by which rocks are now analyzed
+in the laboratory of the United States Geological Survey.
+
+(11) It is desirable to study various obscure chronic conditions, such
+as lathyrism, with a view to determine the inorganic constituents of
+lathyrus and other families of plants.
+
+       *       *       *       *       *
+
+FOOTNOTES:
+
+    [251] Résumé of the results of the loco-weed investigations
+    carried on by the Bureau of Plant Industry was issued as
+    Bulletin 121, part 3, Bureau of Plant Industry, on January
+    28, 1908, in the form of papers by C. Dwight Marsh and Albert
+    C. Crawford, respectively, under the titles "Results of
+    Loco-Weed Investigations in the Field" and "Laboratory Work
+    on Loco-Weed Investigations."
+
+
+
+
+INDEX.
+
+
+
+
+                                                                   Page.
+  Abortion, cows, caused by loco poisoning,                           13
+            rabbits, caused by loco and barium poisoning,     41, 42, 62
+
+  Acid, acetic, found in loco-weed,                                   26
+
+  Acqua, C., reference to work,                                       52
+
+  Africa, South, goat disease,                                        17
+
+  Alfalfa, extract, experiments,                                      28
+
+  Alkali deposits, supposed to cause loco disease,                    11
+
+  Alkaloidal reactions, loco plants,                      20, 23, 27, 28
+
+  Amaranthus graecizans, supposed cause of loco disease,              10
+
+  American Pharmaceutical Association, proceedings, reference,        10
+
+  Ammonia obtained from loco plants,                                  26
+
+  Ammonium sulphid precipitate, effect on rabbits,                    50
+
+  Anæmia, progressing, fundamental characteristic of loco disease,
+                                                                  16, 19
+
+  Analyses of loco plants,                                21, 22, 23, 32
+
+  Anderson, F. W., references to work,                10, 12, 14, 18, 19
+
+  Animals, carnivorous and herbivorous, varying immunity to loco
+             disease,                                                 23
+           domestic, barium poisoning, effects,                       72
+           experiments with barium salts in laboratory,            57-62
+           farm, barium poisoning, effects,                           72
+           locoed, autopsies,           18-19, 24, 26, 30, 34, 36-43, 45
+                   clinical symptoms,                              12-16
+                   pathological conditions as described on the range,
+                                                                   18-19
+           poisoned by barium, autopsies,          57-61, 64, 67, 73, 74
+           young, susceptibility to loco poisoning,                   15
+
+  Antelopes, susceptibility to loco disease,                          12
+
+  Antidote to loco poison, theoretical,                            71-72
+
+  Aragallus lamberti, ash determination,                              54
+                      barium determination,                       54, 56
+                      extracts, uses in laboratory experiments, feeding
+                        animals,     20, 23-25, 37, 42, 44-49, 66-68, 70
+                      properties, investigations,       20-21, 23-25, 32
+            spicatus, study and experiments,                          33
+            spp., cause of loco disease,                       10, 20-34
+                  uses, medicinal and toxic properties,               35
+
+  Arsenic poisoning, references,                                      49
+
+  Ash determinations of loco plants,                               54-55
+      extract from loco plants, experiments,                       48-52
+      loco plants, barium determinations,                          55-57
+                   importance of analysis,                            76
+
+  Astragalus bigelowii, extract, fatal to rabbit,                     38
+             bisulcatus, extract fatal to rabbit,                     38
+             decumbens, extracts, feeding experiments with rabbits,   70
+
+  Astragalus exscapus, barium reported by C. Sprengel,                53
+             hornii, poisonous properties, study,                     19
+             lentiginosus, poisonous properties, study,               19
+             menziesii, stock poisoning,                              20
+             missouriensis, ash content and barium determination,     56
+                            extracts, feeding experiments with
+                              rabbits,                             68-69
+             mollissimus, distillate, composition,                    26
+                          extracts, experiments in feeding animals,
+                                             22, 23-25, 27-33, 36-49, 70
+                          investigations, experiments, and
+                            analyses,                              21-34
+                          physiological action,                22, 24-25
+             mortoni, a deadly sheep poison,                          20
+             nitidus extracts, feeding experiments with rabbits,  38, 69
+             spp., cause of loco disease,                      10, 19-34
+                   total ash determinations,                       54-55
+                   uses, medicinal and toxic properties,              35
+                   varieties containing no barium,                    57
+
+  Australia, disease similar to loco poison, description,          16-18
+
+  Autopsies on animals after barium poisoning,         57-61, 67, 73, 74
+                             loco poisoning,
+                                        18-19, 24, 26, 30, 34, 36-43, 45
+
+
+  Bachem, C., reference to work,                                      50
+
+  Bailey, F. M., reference to work,                                   17
+
+  Barium acetate, feeding experiments on animals in laboratory,    57-62
+         action on farm and domestic animals,                      72-74
+         carbonate, feeding experiments on animals in laboratory, 61, 62
+                                           rats,                      71
+                    hypodermic injection, cats, fatal results,        62
+         chlorid, effects on human beings,                         63-65
+                  feeding experiments with animals in laboratory,  60-62
+                  use in veterinary therapeutics, dangers,         72-73
+         content of rocks in Rocky Mountains,                         54
+         determination in ash of loco plants,                  54, 55-57
+         discovery in loco plants, feeding experiments,                5
+         feeding experiments with range cattle, desirability,         71
+         harmful when in soluble form,                                76
+         in brine, poisoning stock,                                   73
+            well water in England,                                    57
+         insoluble after drying loco plants, extraction with digestive
+           ferments,                                                  76
+         nitrate, feeding experiments on animals in laboratory, results,
+                                                                  61, 62
+         phosphate, analysis by Bureau of Chemistry,                  69
+         poisoning, experimental, pathological lesions,               65
+                    horses, sheep, and pigs,                      73, 74
+                    man, symptoms, results,                        62-65
+         presence in certain vegetable substances,                    53
+         salts, feeding experiments on animals in laboratory,      57-62
+                toxicity of different solutions,                      64
+                         relation of altitude, climate, and varying
+                           combinations,                              65
+                use in medicine,                            62-65, 72-73
+         sulphate, nontoxic on account of insolubility,               53
+
+  Barrows, D. P., reference to work,                                  35
+
+  Bary, A., references to work,                               53, 59, 60
+
+  Baum, reference to work,                                            64
+
+  Beech, barium present,                                              53
+
+  Beer, Mexico, use of "crazy weed",                                  20
+
+  Bellisari, G., reference to work,                                   64
+
+  Beryllium chlorid, effect on rabbits,                               50
+
+  Binet, P., reference to work,                                       59
+
+  Birch, barium present,                                              53
+
+  Birdsall, W. R., experiments with Aragallus lamberti,               20
+
+  Blankinship, J. W., references to work,                         11, 34
+
+  Blood, clots on brain,                              18, 26, 37, 42, 65
+
+  Boehm, R., reference to work,                                       58
+
+  Böhm, C. R., reference to work,                                     50
+
+  Bray, W. C., reference to work,                                     53
+
+  Brewer, W. H., reference to work,                                   20
+
+  Brine, barium content, producing acute poisoning in stock,          73
+
+  Brodie, B. C., reference to work,                                   61
+
+  Brunton, T. L., reference to work,                                  72
+
+  Burgassi, G., reference to work,                                    52
+
+
+  Cæsium chlorid, experiments on rabbits,                             51
+         occurrence in plants, toxicity,                              51
+
+  Calcium acetate, experiments on rabbits,                            52
+          carbonate, antidotal to barium,                             71
+          experiments on rabbits,                                     52
+          occurrence in loco plants,                              25, 27
+
+  Cambier, J., experiments with loco plants,                       26-28
+
+  Canada, disease caused by eating ragwort,                           17
+          freedom from loco disease,                                   9
+
+  Cannabis sativa, supposed cause of locoed conditions in Mexico,     10
+
+  Caprioides aureum, supposed cause of loco disease,                  10
+
+  Carpenter, J. S., references to work,                           63, 64
+
+  Cash, J. T., reference to work,                                     72
+
+  Cats, barium injection experiments,                                 62
+        loco-plant experiments,                               22, 24, 30
+          _See also_ Kittens.
+
+  Cattle, barium feeding experiments under range conditions,
+    desirability,                                                     71
+          daily ration of green fodder, toxic effects of loco plants, 74
+          loco poisoning, notes,                      12, 19, 20, 22, 28
+          locoed, flesh harmless,                                     65
+          poisoned with barium chlorid, flesh harmless,               65
+          range, barium feeding experiments, desirability,            71
+          susceptibility to loco disease,                             12
+
+  Cerium chlorid, experiments on rabbits,                             50
+
+  Chemical experiments with loco plants,                           46-57
+
+  Chemicals in aqueous solution, effects on rabbits,               50-52
+
+  Chemistry, Bureau, ash and barium determinations, loco plants,  54, 56
+
+  Chesnut, V. K., references to work,                         10, 11, 33
+
+  Chevallier, A., reference to work,                                  64
+
+  Christison, R., references to work,                             62, 63
+
+  Coffee substitute, use of seeds of Astragalus boeticus,             35
+
+  Collier, Peter, study of loco plants,                               21
+
+  Colorado, loco disease experiments, results,                         5
+            loss of stock from loco disease, 1898,                     9
+
+  Constipation, treatment of animals with barium, danger,             73
+
+  Cotyledon ventricosa, cause of nenta, a goat disease,               17
+
+  Courtin, reference to work,                                         64
+
+  Cows, abortion caused by loco poisoning,                            13
+        autopsies after loco poisoning,                               18
+        locoed, symptoms,                                             25
+        susceptibility to loco disease,                               12
+
+  Crawford, Albert C., loco investigations, reference to published
+    paper,                                                            75
+
+  Crazy weed. _See_ Loco plants.
+
+  Crotalaria sagittalis, cause of loco disease, chemical
+    study,                                                     10, 26-27
+                         experiments with horses,                  26-27
+
+  Curtice, C., reference to work,                                     31
+
+  Cyon, M., reference to work,                                        59
+
+  Cyprus, loco disease of cattle, sheep, and goats,                   22
+
+
+  Darling pea, effects on horses and sheep in Australia,              16
+               feeding sheep, effects similar to loco poisoning,   16-17
+
+  Day, M. G., experiments with Astragalus mollissimus and Aragallus
+    lamberti,                                                  15, 23-26
+
+  Delphinium spp., supposed cause of loco disease,                    10
+
+  Demoussy, E., reference to work,                                    53
+
+  Didymium chlorid, experiments on rabbits,                           51
+
+  Dieckerhoff, W., references to work,                            72, 74
+
+  Digestion of loco plants, experiments,                  66, 67, 68, 70
+
+  Diuretic, use of Astragalus glycophyllus,                           35
+
+  Dogs, barium feeding experiments, results,                          62
+               poisoning, subcutaneous injection,                     74
+        loco-plant feeding experiments,                   22, 23, 30, 53
+
+  Donkeys, susceptibility to loco disease,                            12
+
+  Dworzak, H., reference to work,                                     53
+
+  Dyrenforth, reference to work,                                      54
+
+
+  Eastwood, A., references to work,                               10, 12
+
+  Eckard, G. E., reference to work,                                   53
+
+  Ehrhardt, J., reference to work,                                    73
+
+  Emory, W. H., reference to work,                                    19
+
+  Eschricht, reference to work,                                       64
+
+  Experiments, laboratory, with barium salts,                      57-62
+                                loco plants,                36-56, 66-71
+               loco poisoning and barium feeding, results,             5
+
+  Extracts of loco plants, digestion with pepsin and pancreatin,
+    experiments,                                                   66-68
+                           testing, importance,                       76
+                           use in laboratory experiments, varying
+                             toxicity,                      36-49, 66-71
+
+
+  Falk, reference to work,                                            74
+
+  Faust, E. S., reference to work,                                    31
+
+  Faville, reference to work,                                         18
+
+  Felletar, E., reference to work,                                    62
+
+  Ferguson, J. C., reference to work,                                 63
+
+  Filippi, E., reference to work,                                     62
+
+  Fletcher, J., reference to work,                                    10
+
+  Fleurot, reference to work,                                         35
+
+  Folin, O., reference to work,                                       56
+
+  Food, use of loco plants,                                       35, 74
+
+  Forage, use of Astragalus nuttallianus and A. crassicarpus,         35
+
+  Forchhammer, J. G., reference to work,                              53
+
+  Foster, F. B., reference to work,                                   26
+
+  Frankforter, G. B., reference to work,                              35
+
+  Fraps, G. S., reference to work,                                    72
+
+  Fresenius, C. G., reference to work,                                72
+
+  Fritillaria pudica, supposed cause of loco disease,                 10
+
+  Frogs, loco-plant experiments,                              17, 22, 24
+         poisoning,                                               17, 24
+
+  Fröhlich, A., reference to work,                                    65
+
+  Fröhner, E., reference to work,                                     73
+
+  Fuchs, C. J., references to work,                               65, 74
+
+  Funaro, A., reference to work,                                      64
+
+
+  Garbanzillo, Spanish name for Astragalus mollissimus, derivation,   11
+
+  Gibbons, H., reference to work,                                     21
+
+  Givens, A. J., references to work,                              10, 35
+
+  Glands, swelling, in locoed animals, note,                          63
+                    result of use of barium on human beings,          63
+
+  Glover, R. M., reference to work,                                   61
+
+  Goat disease, South Africa, note,                                   17
+
+  Goats, loco poisoning,                                              22
+         susceptibility to loco disease,                              12
+
+  Gordon, P. R., reference to work,                                   17
+
+  Grass staggers, Texas loco disease, symptoms, description,          11
+
+  Greshoff, M., reference to work,                                    35
+
+  Guinea pig, autopsy after loco poisoning,                           43
+         pigs, loco-plant feeding experiments,                    32, 43
+
+  Guthrie, F. B., reference to work,                                  17
+
+
+  Hairs on plants cause of loco disease, suggestion,              22, 28
+
+  Hallucinations caused by loco poison,                               13
+
+  Hare, H. A., reference to work,                                     63
+
+  Harkins, W. D., reference to work,                                  49
+
+  Hayes, M. H., description of Texas grass staggers,                  11
+
+  Hefftner, A., reference to work,                                    58
+
+  Heilborn, F., reference to work,                                    59
+
+  Hill, J. R., reference to work,                                     22
+
+  Hillebrand, method of determination of barium in ash of loco
+    plants,                                                           56
+              statement as to barium content of rocks in Rocky
+                Mountains,                                            54
+
+  Hoffmann, F., reference to work,                                    26
+
+  Hogs, susceptibility to loco disease,                               12
+
+  Holmes, E. M., reference to work,                                   35
+
+  Hornberger, R., reference to work,                                  53
+
+  Horses, autopsies after barium poisoning,                           73
+                          loco poisoning,                         18, 26
+          barium poisoning,                                           73
+          disease caused by feeding on Darling pea (Swainsona
+            galegifolia),                                             16
+          loco-plant experiments,                                     33
+          loco poisoning, notes,                          16, 19, 20, 26
+          locoed, symptoms,                                           13
+          susceptibility to loco disease,                             12
+
+  Hough, W., reference to work,                                       35
+
+  Howard, C. D., reference to work,                                   73
+
+  Hugo, Colo., soils, analysis for traces of barium,                  57
+
+  Hunt, Reid, study of and experiments with loco plants,           33-34
+
+  Hurd, H. M., reference to work,                                     35
+
+  Husemann, T., reference to work,                                    62
+
+  Hydrocyanic acid, presence in loco plants, suggestion,              29
+
+
+  Indigo disease, similarity to loco disease,                      16-17
+
+  Ingersoll, study of loco disease,                                   30
+
+  Injections, subcutaneous, experiments with barium salts,    62, 73, 74
+                                             loco extracts,           43
+
+  Insanity, treatment, use of Astragalus mollissimus,                 35
+
+  "Insect Life," reference to work,                                   31
+
+  Intoxication caused by loco plants,                     13, 16, 21, 22
+
+
+  Jaksch, J. v., references to work,                              51, 62
+
+  Janvier, reference to work,                                         11
+
+
+  Kabitz, H., reference to work,                                      74
+
+  Kansas, loss of stock from loco disease in 1883,                     9
+
+  Kellogg, A., reference to work,                                     19
+
+  Kelsey, F. D., reference to work,                                   10
+
+  Kennedy, H., reference to work,                                     63
+
+  Kennedy, J., experiments with loco-weed extracts,               23, 26
+
+  Kingsley, B. F., reference to work,                                 12
+
+  Kissner, G., reference to work,                                     61
+
+  Kittens, loco-plant experiments, and autopsies,                  24-28
+    _See also_ Cats.
+
+  Kleuch, J. P., reference to work,                                   19
+
+  Knop, W., reference to work,                                        53
+
+  Knowles, M. E., references to work,                             13, 14
+
+  Kobert, R., references to work,                                 33, 54
+
+
+  Laband, L., reference to work,                                      51
+
+  Laboratory experiments with loco plants,                         36-57
+
+  Lagarde, P., reference to work,                                     64
+
+  Lambs, experiments in feeding loco plants, symptoms and autopsies,
+                                                              31, 45, 46
+
+  Lane, C. B., reference to work,                                     74
+
+  Lanthanum chlorid, experiments on rabbits,                          50
+
+  Lathyrism, symptoms, resemblance to loco poisoning,                 15
+
+  Leucocrinum montanum, supposed cause of loco disease,               10
+
+  Lewin, L., references to work,                                  65, 72
+
+  Lewis, Doctor, experiments with loco plants on rabbits,             30
+
+  Linossier, G., reference to work,                                   74
+
+  Lisfranc, reference to work,                                        64
+
+  Lloyd, J. W., study of loco poison,                             31, 32
+
+  Loco-acid, body supposed to be in loco plants,                      30
+       disease, attributed to hairs on plants,                    22, 28
+                              worms,                              31, 34
+                experiments, Colorado, results,                        5
+                symptoms, descriptions,
+                                11, 12-16, 17, 24, 26, 28, 29, 33, 36-44
+       eating habit, description,                                 14, 15
+       intoxication,                                      13, 16, 21, 22
+       investigations from a pharmacological standpoint, historical
+         sketch,                                                   19-34
+       plants, ash determinations,                                 54-55
+               ashed, aqueous extracts, effect,                    48-52
+               barium determinations,                              55-57
+               eaten with large amounts of other food presumably not
+                 dangerous,                                           71
+               effects on human beings,                   15, 20, 22, 35
+               extracts, digestion with pepsin and pancreatin,
+                 experiments,                                      66-68
+               extracts, variations in toxicity,                   66-71
+                         use in laboratory experiments, varying
+                           toxicity,                        36-52, 66-71
+               list,                                                  10
+               poison, varying in carnivorous and herbivorous
+                 animals,                                             23
+                               with season, variety, and origin,  25, 48
+               uses as food, forage, medicine, etc.,                  35
+               without barium not poisonous,                       68-71
+                 _See also_ Loco weeds.
+       poison, attempts to isolate the active principle,              47
+       poisoning, laboratory study, results,                         5-6
+                  symptoms,     11, 12-16, 17, 24, 26, 28, 29, 33, 36-44
+                           reproduction in rabbits,    29, 33, 36-44, 75
+                  theoretical antidote,                            71-72
+
+  Locoed animals, clinical symptoms,                               12-16
+                  pathological conditions as described on the
+                    range,                                         18-19
+         derivation of term,                                           9
+
+  Locoin, experiments by Ruedi,                                       30
+
+  Loco-weed disease, geographical distribution,                        9
+            family, notes on use of various members,                  35
+              _See also_ Loco plants.
+
+  Lopes, A., reference to work,                                       64
+
+  Lotus americanus, supposed cause of loco disease,                   10
+
+  Lüdeking, C., reference to work,                                    72
+
+  Lutterkorth, H., reference to work,                                 53
+
+
+  McCullaugh, F. A., references to work,                  12, 13, 15, 19
+
+  McEackran, Doctor, loco-plant experiments with horse,               33
+
+  Magnesium acetate, experiments on rabbits,                          52
+
+  Magnus, R., reference to work,                                      58
+
+  Maiden, J. H., reference to work,                                   16
+
+  Maisch, J. M., references to work,                              21, 35
+
+  Malbec, A., reference to work,                                      58
+
+  Malnutrition, cause of loco disease, suggestion,                29, 34
+
+  Malvastrum coccineum, supposed cause of loco disease,               10
+
+  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
+
+  Plönius, 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
+
+  Schwilgué, 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 THE PROJECT GUTENBERG EBOOK 40256 ***