throbber

`
`
`
`TREASURY DEPARTMENT
`
`
`PUBLIC HEALTH
`REPORTS
`
`ISSUED WEEKLY
`BY THE
`
`UNITED STATES, PUBLIC HEALTH SERVICE
`
`
`CONTAINING INFORMATION ON THE CURRENT
`PREVALENCE OF DISEASE, THE PREVENTION
`AND CONTROL OF DISEASE, AND
`RELATED SUBJECTS
`
`
`
`Page 1 of 38
`
`
`VOLUME 43—PART 1
`NUMBERS 1-26
`
`JANUARY-JUNE, 1928
`
`#3
`
`UNITED STATES
`GOVERNMENT PRINTING OFFICE
`WASHINGTON
`1928
`
`Elysium Health Exhibit 1015
`Page 1 of 38
`
`

`

`|| | A
`
`DDITIONAL COPIES
`OF THIS PUBLICATION MAY BE PROCURED FROM
`THE SUPERINTENDENT OF DOCUMENTS
`U.S.GOVERNMENTPRINTING OFFICE
`WASHINGTON, D, C.
`AT
`5 CENTS PER COPY
`
`MO MATTsS MOVs LON
`
`oer
`
`
`
`Vennbagi
`
`WURKSS
`
`Elysium Health Exhibit 1015
`Page 2 of 38
`
`

`

`
`
`PUBLIC HEALTH REPORT
`
`VOL. 43
`
`JUNE 8, 1928
`
`NO. 23
`
`A STUDY OF THE BLACKTONGUE-PREVENTIVE ACTION
`OF 16 FOODSTUFFS, WITH SPECIAL REFERENCE TO THE
`Bes OF BLACKTONGUE OF DOGS AND PELLAGRA
`
`F MAN
`
`.
`
`Page
`Page
`InneGideaeeee T38058|FE13 Qe|tee Nee ee rec ewrer 1424
`Methods and criteria_.___-
`‘
`133Agl@
`POLK livotece. _ tyeees oaeen 1428
`
`
`Maize (aud cornstarch)__
`Canned salmon
`1420
`
`Wheat:
`Hee yolk.
`1431
`
`Wheat germ __
`Tomatoes
`1434
`
`
`Cowpea. __-
`Carrots
`1433
`Og DOME eee eee een
`Hiutlabagas 22.82.) 8 coe
`~
`1443
`
`Relation of blacktongue to pellagra......-...
`Milk ea
`1446
`Summaryand conclusions____
`--
`Butter_.____
`1447
`Ralerences252. 8aTe 1448
`Cod-liveroil
`
`Tables_....____ 2M8 to. oe coe aa 1449
`Cottonseed oil____
`
`
`
`
`and R. D. Linu
`By JosErH GotpperGer and G. A. WHeErer, Surgeons,
`and L. M. Rogers, Passed Assistant Surgeons, United States Public Health
`Service
`
`
`CONTENTS
`
`Some of the results of our study of the problem of an experimental
`animal for pellagra were briefly summarized in a communication
`published two years ago (1), and have been presented in detail in
`two recent publications.
`In the first of
`these Goldberger
`and
`Wheeler (2) reported the production in the dog, by feeding pellagra-
`producing diets, of a pathological condition considered by them to be
`identical with the spontaneously occurring canine disease known to
`American veterinarians as blacktongue.! The clinical resemblance of
`this canine disease to pellagra in man was discussed and was consid-
`ered sostriking as to be, in itself, practically conclusive of the identity
`of these two conditions.
`In harmony with and supporting this view
`was also the suggestion of a common etiology indicated by the success-
`ful production of the canine disease by feeding with pellagra-producing
`diets.
`In the second communication, Goldberger, Wheeler, Lillie,
`and Rogers (3) reported a series of feeding experiments with yeast
`from the results of which they concluded that experimental black-
`tongue is due to a deficiency in diet that is capable of being corrected
`by something present in abundance in yeast. This demonstration of
`the presence of the blacktongue preventive in yeast, a substance in
`which the pellagra preventive (factor P-P) was also known to be
`present in abundance (4), was considered to increase somewhat the
`
`Elysium Health Exhibit 1015
`Page 3 of 38
`
`

`

`
`
`June 8, 1928
`
`9
`1386
`
`In this connectionitis of interest !to note! that Denton
`conditions.
`(5), in a study of the tissue changes in experimental blacktongue, has
`found that the lesions of the skin, meuth, pharynx, esophagus, and
`colon in the canine disease are very similar to those in pellagra, and
`that histologically the lesions in experimental blacktongue duplicate
`those in pellagra.
`In the body of this report reference will be made to differences
`between certain of the results of our study and those of an apparently
`similar study by Underhill and Mendel (6). The divergence in our
`results is of interest, since we have heretofore considered it highly
`probable that the pathological condition experimentally indueed in
`the dog by Chittenden and Underhill and studied by Underhill and
`Mendel was identical with the experimental condition studied and
`identified by us as blacktongue (2). The extensive report of their
`work (7) which has just come to our attention presents some clinical
`details which not only seem in themselves significant of a difference
`in the two pathological conditions, but also suggest that we had here-
`tofore, perhaps, underestimated the significance of certain otherclin-
`ical differences. Thus we find in this report that a ‘troublesome
`skin rash’ appears to have been commonin the condition with which
`Underhill and Mendel have worked. We have encountered none
`such in our dogs. On the other hand, while we have observed a
`pellagra-like dermatitis of the scrotum in some 40 to 50 per cent of
`attacks in our male dogs, there is no mention of the occurrenceof
`such an eruption in the condition studied by Underhill and Mendel,
`Again, in the condition studied by us—namely, blacktongue—there
`is a definitely marked febrile stage which does not seem to occur in
`the Chittenden-Underhill syndrome studied by Underhill and Men-
`del; for they nowhere make mentionof it, not even intheir fullreport.
`These clinical differences seem to us of such importancethat, in spite
`of the striking clinical similarity in certain other respects, doubt Boy
`arises as to the identity of the Chittenden-Underhill ‘pellagra-like’
`syndrome. Until this doubt is definitely resolyed one wayor another,
`it would seem premature to discuss, and we therefore do not atone
`to discuss, the differences between the results reported by Underhill
`and Mendel and those recorded by ourselves in the present and in a
`preceding communication (3).
`surat
`In the present communication we present some further rae
`our study of experimental blacktongue. These results deal with t ne
`blacktongue preventive potency of certain selected toesieee ie i
`number, with special reference to the relation of experimenta black:
`
`
`
`1387
`
`June 8, 1928
`
`METHODS AND CRITERIA
`The general methods of caring for and feeding our experimental
`animals haye already been deseribed (2) (3). We may recall, how-
`ever, that the experimental diets were, as a rule, freshly prepared each
`day. The daily allowance of food was, in general, intended to be no
`more than enough for the maintenance of normal body weight. An
`exception was made in the case of young growing animals, to which
`more than this allowance wasoffered.
`It may be recalled, too, that
`it has been our practice to use our dogs repeatedly with or without
`intermediate periods of stock feeding as might be demanded by the
`purposeof the experiment.
`In stock feeding, a definite food mixture
`has been used, principally our diet No. 156,
`the composition and
`evidence of the adequacy of which have been given in a preceding
`comniunication (2),
`In testing for the blacktongue preventive we have employed both
`the curative and the preyentive procedure, singly or in combination.
`Since, as we havein a preceding communication (2), already indicated
`the clinical course of experimental blacktongue, especially in the inva-~
`sional stage, may normally be of an intermittent or relapsing char-
`acter, we attach no significance to a seemingly favorable therapeutic
`result in cases in which the treatment is begun early unless confirmed
`by the results of a preventive test. On the other hand, consistently
`unfavorable results of treatment under such favoring circumstances
`have been considered trustworthy indications of a povertyin orlack
`of the blacktongue preventive, provided that the test dose has been a
`liberal one. Our experience with experimental blacktongue has led
`us to consider the rise in temperature which occurs in the advanced
`stage of the disease as a mark of gravity (2). Only very exceptionally
`does the attack normally remit after this temperature rise has taken
`place. We have, therefore, been disposed to considerclinical recovery
`from the attack (that is, disappearance of all manifestations of the
`disease with recovery of appetite) following treatment begun at this
`advanced grave stage as significant, but have, nevertheless, always
`required confirmation by the preventive test before drawing final
`conclusions with respect
`to the presence of the preventive in the
`substance thus found to be active.
`Isolated cases of the apparent
`failure of treatment underthese unfavorable circumstances have been
`considered as without significance.
`In testing the individual foodstuffs, one, or exceptionally both, of
`two types of test diet have been employed.
`In the first the com-
`ponents other than the foodstuff under investigation are believed to
`
`ri
`
`Elysium Health Exhibit 1015
`Page 4 of 38
`
`

`

`
`
`
`
`June 8, 1928
`
`1388
`
`4
`
`basic diet should be kept in mind in evaluating and comparing the
`indications of preventive potency, since the results yielded by the
`former may probably be considered as due virtually entirely to the
`action of the foodstuff tested, whereas those of the latter must be
`considered as a summation effect due to the combined action. of the
`basic components andof the test foodstuff.
`So far as our data permit, an appraisal has been made of the
`blacktongue preventive potency of each foodstuff.
`In view of the
`lack of a better practicable standard for such purpose, our appraisal
`is simply a judgment, in broad terms, of the preventive adequacyof
`such a quantity as, according to conventional practice, represents
`the daily allowance for an average adult human male.
`:
`The experimental disease in the dog and its diagnosis have been
`describedin a preceding report
`(2); we need recall only that the
`earliest distinctive buccal signs are a vivid red injection of
`the
`mucosa of the floor of the mouth or a peculiar reddening of the
`mucosa of
`the upper lip in the formof bilaterally symmetrical
`patches, or of both. We have considered the first appearance of
`these mouth lesions as marking the beginning of the attack of black-
`tongue. We have conformed to this rule in all cases, even in those
`relatively few instances in which the pellagralike dermatitis of the
`scrotum appeared in advance of the mouth lesions. Thus marked,
`the beginning of the experimental disease, when this is induced by
`feeding our basic diet No. 123 (or certain of its modifications, namely
`diets No. 209, No. 195, and No. 268), is only very exceptionally de-
`layed beyond about 60 days, after the beginning of the feeding 2).
`We have therefore been inclined to consider a very notable Be;
`longation of this period, particularly when manifested in more ce
`one of a group of test animals, as significant of the presence in the
`test diet of the blacktongue preventive in an amount that 4 Sora
`what larger than that presumably contained in our standard basic
`diet.1 Since other factors, not. yet understood, such, for np af
`self-imposed starvation or semistarvation and other Doser
`existing deficiencies or maladjustments of dietary psa? 8) oe
`and probably do influence the duration of what for conspnlenegmn
`be designated as the deprivation period, we have tried
`to e:
`due caution in the interpretation of such indications.
`ontain, we judge,
`-
`"
`7
`1 Our basic experimental diets of the type exemplified by our diet No. me OSyeante aeatualls aint
`a small smountof the blacktongue preventive derived from its magicalioe fof varifiod foodstuffs which,
`
`
`
`
`1889
`MAIZE
`
`Tune8, 1928
`
`The idea that the maize in thediet is in some way concertied in
`the causation of pellagra has, as is well known, been entertained by
`students of that disease almost from the timeof its first recognition,
`It seems to havearisen in part, at least, because maize constituted a
`very large part of the diet of the populations among whom,in the
`Old World, the disease was endemic.
`In the United States, maize
`also is @ conspicuous element in the diet of the population in the
`area where the disease is most prevalent. Both in the Old andin
`the New World, therefore, maize is more or less prominently asso-
`ciated with the occurrence of pellagra. While the extreme position
`of certain zeists that there is no pellagra without maize is now no
`longer tenable, the association is no doubt very common. One is
`justified in concluding, therefore, that maize is very poorin or lacks
`the pellagra preventive.
`In constructing our experimental diets, based as they are on diets
`foundin association with the occurrence of pellagra, maize was from
`the first included as a conspicuous element, The basic dict most
`frequently used by us forthe experimental production of blacktongue
`(diet No. 123, shown in Table 1) contains 400 grams of maize meal
`per 2,400 calorie ration. This is a large amount of cereal, consti-
`tuting as it does two-thirds of the weight of the dry ingredients of
`the diet. Notwithstanding this, however, as has in a preceding com-
`munication (3) already been set forth, dogs fed this diet (ineluding
`certain of its modifications) have developed blacktongue within a
`period which only exceptionally exceeded a duration of about 60
`days. This would indicate that, as measured by the requirements
`of the dog, maize containslittle if any of the blacktongue preveative.
`Incidentally, it may be noted that cornstarch would also appear to
`be very poor or lacking in the blacktongue preventive since, as pre-
`viously reported (3), two dogs fed a diet (No. 281) containing 366
`gramsof cornstarch per 2,400-calorie portion promptly developed the
`The maize meal used in our basic diet No, 123 (including its modi-
`fications) does not, however, represent quite the whole kernel, since
`a small part of the bran is removed by sifting as if for human con-
`sumption.
`It seemed desirable, therefore, to test a meal from which
`nothing had been taken away. But as it did not seemto us probable
`that the difference in the meal represented by the small amount of
`
`disease.
`
`Elysium Health Exhibit 1015
`Page 5 of 38
`
`

`

`
`
`June 8, 1928
`
`1390
`
`EXPERIMENT 1
`
`This was a test of the blacktongue preventive action of whole white
`maize meal which was incorporated in test diets No. 149 and No.
`149A.
`(Table 2.) These diets, which are identical except that the
`butterfat of one is quantitatively replaced by cod-liveroil in the other,
`are a slight modification of a maize diet studied by McCollum, Sim-
`monds, and Pitz (8), and by them considered complete for normal
`growth of the rat to normal adult size, and for that reason selected
`by us for this study. Each contains 450 grams of whole-maize meai
`in a ration ofslightly less than 2,400 calories. Suitable portions of
`one or the other of these diets were offered daily to each of seven test
`animals, dogs 29, 40, 52, 54, 57, 65, and 73.
`Oneof these dogs served
`during two separate periods, so that eight tests in all are to be con-
`sidered. The significant details relating to each of the test animals
`are presented in the following:
`Dog 29.—Male. Acquired May 9, 1923, between which date and January 11,
`1924, served in a number of experiments and suffered four attacks of blacktongue,
`the latest of which began January 7, 1924. On a miseellaneous stock diet from
`January 11 to February 5, 1924.
`February 5, 1924: In good condition; weighs 11.1 kilograms; begins test dict
`No. 149.
`(Table 2.)
`On February 17, 1924, at the end of a period of 12 days, presented the first signs
`of an attack of blacktongue, an injection of the floor of the mouth. Further
`history not relevant.
`Dog 40.--Male. Whelped in the laboratory June 26, 1923, and reared on a
`stock diet. Up to February 20, 1924, served in a number of experiments and
`suffered two attacks of blacktongue, the later one of which began February 19,
`1924. On a stock diet for reconditioning from February 20 to March 11, 1924,
`March It, 1924: In good condition; weighs 9.2 kilograms; begins dict No. 149.
`On April 23, 1924, at the end of a period of 43 days, presented the first signs of
`an attaek of blacktongue, an injection of the floor of the mouth. Weight was
`11 kilograms. Further history not relevant.
`Dog 52.—Biich. Aequired September 25, 1923. Up to February 20, 1924,
`served in a number of experiments andsuffered two attacks of blacktongue, the
`later one of which began February 18, 1924. On a stock diet for reconditioning
`from February 20 to March 11, 1924.
`March 11, 1924: In good condition; weighs 9.7 kilograms; begins test diet No. 149.
`Qn July 31, 1924, at the end of a period of 142 days, presented thefirst signs of an
`attack of blacktongue, an injection of the floor of the mouth. Weighs 10
`kilograms, Further history not relevant.
`Dog 54.—Bitch. Acquired September 25, 1923. Up to January 11, 1924,
`served in a number of experiments and suffered an attack of blacktongue which
`began November 28, 1923. On reconditioning diets from January 11 to March
`25, 1924.
`Im good condition; weighs 8.1 kilograms; begins test diet No.
`March 25, 1924:
`149A.
`(Table 2.)
`:
`On June 5, 1924, at, the end of a period of 72 days, presented the first signs of an
`
`June 8, 1928
`1391
`Dog 67.—Male. Acquired September 25, 1923. Up to January 15, 1924,
`served in a number of experiments and suffered two attacks of blacktongue, the
`latter of which began December 13, 1923. From January 15 to February5, 1924,
`on a miscellaneous stock diet for reconditioning,
`ro 5, 1924: In good condition; weighs 9.7 kilograms; begins test diet
`o. 149.
`On February 23, 1924, at the end of a period of 18 days, presented thefirst signs of
`blacktongue, an injection of the floor of the mouth, of the mueosa of the
`cheeks, and of the anterior faucial pillars. Weighs 10 kilograms. Begins
`reconditioning diet.
`February 25, 1924: Redness of mucosa of the floor and cheeksis less pronotticed.
`February 26, 1924: Redness has practically completely faded. Weighs 9.9
`kilograms.
`March25, 1924: In good condition; weighs 10.1 kilograms; begins test diet No.
`149A.
`On April 11, at the end of a period of 17 days, presented the beginning signs of an
`attack of blacktongue, an injection of the floor of the mouth. Further history
`not relevant.
`:
`Dog 65.—Bitch. Acquired January 28, 1924. Kept on a miscellaneous stock
`diet to February 5, 1924.
`February 5, 1924: In good condition; weights 6.7 kilograms; begins test diet
`No. 149.
`April 22: Weighs 7.7 kilograms.
`OnApril 27, 1924, at the endof a period of 77 days, presented the first signs of an
`attack of blacktongue, a reddening of the mucosa of the floor of the mouth.
`Further history not relevant.
`Onstock diet up to April 1, 1924.
`Dog 73.—Bitch. Acquired March 19, 1924.
`April 1, 1924: In good condition; weighs 7.7 kilograms; begins test diet No. 149A.
`July 8, 1924: Weighs 10.2 kilograms.
`On July12, 1924, or 102 days after beginning the test, this animal presented an
`injection of the mucosa of the floor of the mouth suggestive of a. beginning
`attack of blacktongue. Two days later this was no longer perceptible, nor was
`there any reappearance of signs of blacktongue during a further period of
`observation of 88 days whieh ended August 19, 1924, on which date this
`experiment was discontinued.
`Resulis and conclusions—Six of the seven dogs developed black-
`tongue in from 12 to 142 days after beginning the test. The seventh
`(dog 73) presented evanescent evidence very suggestive but not con-
`clusive of blacktongue at
`the end of a period of 102 days. The
`observation of this animal was discontinued at the end of 140 days,
`so that the possibility is not excluded that a definite attack of black-
`tongue would have developed had the observation period been longer.
`One of the test animals (dog 57) served during two separate periods
`and developed an attack of blacktongue in each. Thus the six
`animals in which definite evidence of blacktongue developed experi-
`enced,
`in all, seven attacks.
`Six of these appeared at the end of
`periods of not over 77 days in duration, and the seventh (dog 52)
`at the end of a period of 142 days.
`
`Page 6 0
`
`Elysium Health Exhibit 1015
`Page 6 of 38
`
`

`

`. Page7of 38
`
` June8, 1928
`
`
`tion period in the latter was but 140 days, suggest, by contrast with
`our experience wilh basie diet No. 123 (including certain of its
`modifications (3)), that the test diets under consideration may have
`possessed slight preventive properties. The difference is not very
`notable and, such as it is, ean not be attributed, altogether at least,
`to the character and increased quantity of the maize, since ono of
`the test diets (No, 149), unlike our standard basic diet (No. 123),
`contained some butter, which, as will presently be seen, while a poor
`source is not entirely devoid of the preventive factor, a fact that was
`not fully appreciated when this experiment was planned.
`This
`experiment is therefore not conclusive, Notwithstanding this, how-
`ever, the evidence quite clearly indicates that, at best, this cereal is
`a very poor source of the blacktongue preventive.
`Reealling the indications of its poverty in or lack of the pellacra
`preventive if would appear that maize, if it contains any, is a poor
`source of the preventive for both blacktongue andpellagra,
`WHEAT
`The important place among the cereals held by wheat and a desire
`to compare it with maize led us to test its blackiongue preventive
`potency. The following experiment was accordingly carried out,
`
`
`
`EXPERIMENT 2
`
`For the present purpose, wheat ground in this laboratory into a
`meal was, without sifting, incorporated in a diet, No. 128, the com-
`position of which is shown in Table 3. This, as may be seen by refer-
`ence to Table 1, is essentially dietNo. 123, the maize moal of which
`has been quantitatively replaced by the ground wheat, of which there
`are, therefore, 400 grams in each 2,400-calorie portion. Some of this
`diet was daily offered to eachof eight test animals—dogs 5, 9, 13,14,
`29, 38, 44, and 47. The significant details relating to each arebriefly
`as follows:
`Dog 6.—Bitch. Acquired November 8, 1921, Hag served in a numberof
`experiments and has suffered two aftaeks of blacktongie, the lnter one of which
`began August 28, 1923. On stock diet from September 8, 1923, to January 29,
`1924, Whelped a litter of seven pups November 25, 1923, six of which sur-
`vived and were weaned in good condition January 17, 1924,
`January 29, 1924: In good condition; begins diet No. 128.
`(Table 3.)
`‘oat
`On August 2, 1924, at the end of a period of 186 days,. presented the a signs
`of blacktongue, a reddening of the mucosa of the cheeks,
`To this bheére Lp
`added on August 3 a reddening of the mucosa of the floor of the euoueh and
`o
`that of the upper lip on the left side. Further history is not paerens bats,
`Dog 9.—Male. Acquired April 1, 1923, Has served in a number o ater
`ments and has suffered four attacks of blacktongue of whichthe latest
`began
`February 12, 1924. On stock diet from February 13, to March 11, 1924.
`
`June 8, 1923
`1393
`On July 31, 1924, at the end of a period of 142 days; presented thefirst signs of an
`attackof blacktongue, a reddened patch on the mucosa of the upper lip, in the
`region of the canines, on each side, and a slight reddening of the mucosa of the
`floor of themouth, Further history ig not relevant.
`Dog 18.—Male. Aequired April 7, 1923, Up to November 28, 1923, served
`in several experiinents and suffered three attacks of blacktongue, of which the
`latest began November 24,1923. On a reconditioning dict from November 28
`to December 11, 1923.
`'
`December 11, 1928: In good condition; begins diet No. 198.
`On February 20, 1924, or af the end of a period of 71 days, presented an injection
`of the floor of the mouth which was slightly more Pronounced the next day,
`February 21, This reddening then persisted without notable change for some
`48 hours, then rapidly faded so that the mouth was normal on February 25.
`On July 11, or at the end of anadditional period of 142 days, presented renewed
`, 4n erythematous pateh on the mucosa of the upper lip
`on eachside in the region of the canines anda slight reddening of the floor of the
`mouth. Vurther history not relevant.
`Dog 14.—Male, Aequired April 7, 1923. Up to November 28, 1923, served
`in several experiments and suffered four attacks of blacktongute, of which the
`latest began October 30,1923. Ona reconditioning diet from November 28 to
`December 11, 1923,
`December 11, 1923: Tp go0d condition; begins diet No, 128,
`
`of the mouth, Purthey history not relevant.
`Dog 29.—Male. Acquired May 9, 1923. Up to November 27, 192
`in several experiments and suffered three att
`3, served
`acks of blacktongue, of which the
`latest began Oetober 18, 1923. On a recon
`ditioning diet from November 27
`to December 11, 1993.
`December11, 1928: In Sood condition; begins diet No. 128.
`On January 7, 1924, at the end of @ period of 27 days, presented the first signs of
`an attack of blacktongue, a reddening of the mucosa of the floor of the mouth,
`Dog 388.—Male, Whelped in the laboratory June 26, 1923. Lp to February
`20, 1924, served in several experiments and suffered two attacks of blacktongue,
`the-seeond one of which began Vebruary 14,1924. Ona reconditioning diet from
`February 20 to March 11, 1924,
`Mareh 11, 1924: In good condition; beging diet No. 128,
`OmJune 24, 1924, at the end of a period of 105 days, presented the first signs
`of an attack of blacktongne, a reddening of the floor of the mouth, Turther
`Dog,44.-—Male, Whelpedin the laboratory June 26, 1923. Upto: December
`27, 1923, served in one experiment and suffered an attack of blacktongue whith
`began October 28, 1923. On a reconditioning diet from December 27, 1923,
`to January 29, 1924.
`January 29, 1924: Tn good condition; begins diet No. 128.
`On August 13, 1924, at the end of a period of 197 days, presented the first signs
`of an attack of blacktongue, reddened patches on the mucosa of the upper
`lip on each side, Further history not relevant,
`Dog 47,.—Male, Acquired August 18, 1923. Up to November28, 1923, served
`in an experiment and suffered an attack of blacktongue, which began September
`28, 1923. Ona reconditioning diet from November 27 to December 20, 1923.
`
`history not relevant,
`
`Elysium Health Exhibit 1015
`Page 7 of 38
`
`

`

`
`
`
`
`
`
`K
`1395
`Tune 8, 1999
`On January 7, 1924, at the end of a period of 18 days, presented the first signs
`Maen dogs 54, 61, 65, 70, 71, 78, 86, 87, and 88. The significant
`of an attack of blacktongue, a reddening of the floor of the mouth. Turther
`etails relating to each are presentedin the following:
`i
`history not relevant.
`here Acquired September 25, 1923. Up to June 17, 1924, served
`Results and conclusions.—Asis ovident, all eight of the test animals
`a experiments and suffered two attacka of blacktongue of which the
`developed blacktongue..It is noteworthy, however, that in but two
`ris e i an ‘ 1924. ae diet for reconditioning from June 17 to
`of the dogs did the attack have its onset at the end of periods shorter
`23,
`1924,
`expermental
`diet, which include
`:
`sl tiki Maceo
`;
`ch included some wheat germ, from,
`than 71 days.
`Infive of the cight animals thefirst signs of the attack
`Greeao = ee one begins wheat-germ diet No. 197.
`(Table 3.)
`made their appearance at the end of periods varying between 105 and
`er
`19,1925, at
`the end of 136 days, this animal
`y
`ight
`|
`197 days—that is, after periods very definitely longer than is the
`ae aiggestive reddening of the mucosa of the floor of the mouth, which bis
`te
`presented a slight }
`4
`rule in the case of dogs fed diet No. 123. This delay in the develop-
`ss a as no longer perceptible 24 hours later. No further evidence miggoctsYh
`ment of the disease would appearto indicate that diet No. 128 had
`= parescheeared during the remainder of the pertod of observation mhioh
`exercised appreciable but incomplete blacktongue preventive action
`ended May 26, 1926.
`Tn good condition at the end of one year
`th
`te
`pes
`¥y
`on
`the wheat
`and, therefore, that whole wheat contains the blacktongue preven tive,
`Dog 61—Male. Whel
`i
`but in small amount. Compared with the result of the experiment
`-
`petl in the laboratory November 4, 1923,
`7
`ae _ served inone experiment andsuffered one attack of meektbiighetick
`with whole maize, the outcome of the test of whole wheat suggests
`Sars sre 32s On reconditioning diet from May 27 to July 23 1924
`that this is probably a slightly better source of the blacktongue
`a
`July
`23, 1924, to May 26; 1925, on an experimental diet, which i
`if I
`considerable amount of wheat germ.
`sehgl
`preventive than is the maize.
`eee 26, siete In. good condition; begins wheat-germ diet No, 197
`WHEAT GERM
`at canbe 5, 1926, or at the end of a period of 224 days, there ers noted the
`3 8 weia ee attack of hlacktongue, which ended in death on Janvary20 1 926
`* og
`:
`itch. Acquired January 28, 1924, Up to May 27, 1924 sevyvedI
`Feetaeaoe es an attack of blacktongue, Onstock dietfor reron-
`oning
`irom May 27'to July 23,1924, On an experi
`al
`di
`iol
`dnthudd
`Miia germ fromJuly 23, 1924, to May26, 1925 Neee
`ay 26, 1925: In good condition: be i
`2
`i
`i
`197
`)
`gins wheat-germ diet No.
`3
`:
`g
`et
`No, 197,
`;
`€ ee aa at the end of 253 days, this animal presented a slight but
`; ae sie reddening of the mucosa of the floor of the mouth and of the che kk
`wi mn
`» however, had completely faded 24 hours later. Noturther evidence n
`aeainineieeesrpssee during theremainderof theperiadof haeesaon
`th
`ended May £
`iti
`ee ee F
`In good condition at the end of one year on the
`Dog 70.—Male. Whelped in the laho
`if
`E
`oratory November 25, 1923. Up to
`May
`Iped
`|
`:daqiheocesM6 and suffered an attack of binehtania ye
`13,
`May
`|
`On stoek diet for revenditionin
`14
`to
`J
`1924.
`3
`:
`Ba
`i
`b
`:
`;
`g from May 14 to
`:
`eat ) On an experimental diet, which included wheat gern frei Jul aie a
`o May 26, 1925.
`,
`¥ 23, 1924,
`one
`1925: In good condition; begins wheat-germdiet No. 197,
`oe ee aa i 1925, or at the end of a period of 112 days, presented the first
`: os . - a of hlacktongue, reddened lesions on the niucosn of the upper
`P Opposite
`the canines, and an injection of the floor of the mouth
`Further
`ustory not-relevant,
`inie
`ee erein the laboratory November 25, 1923.
`Reared on
`‘eHancous stock diets.
`nan experi
`bal
`di
`hich
`in
`led when
`gi
`feaah aly We toe ioe ee imental diet, which ineluded wheat germ,
`ae 26, 1028: Bh good condition; begins wheat-germ diet No, 197
`‘ay 26, ‘me Completes one year on the wheat-germ diet im good condition: has
`Renee 7 ee evidence of blacktongue durin2 the year
`
`the blacktongue-preventive action of ether-
`This was a test of
`extracted wheat germ. The wheat germ was a commercial product
`from which we had extracted the fat by percolation with ether
`(U. S. P.) at air temperature.’
`It was incorporated: in a diet, No.
`197,
`the composition of which is shown in Table 4. As may be
`seen, each 2,400 calorie portion contains 180 grams of the extracted
`germ.
`It may be noted, too, that it contains a considerable amount
`of cornstarch; notably less, however, as was noted in the preceding
`section in connection with maize, than has been found to be lacking
`in appreciable blacktongue-preventive action. This diet is some-
`what similar to ourbasic diet No. 123 (Table 1), from whichit differs
`notably, however,
`in that the wheat germ and the starch of
`the
`former completely replace the corn meal and cowpeas of the latter.
`
`June8, 1928
`
`1394
`
`While the preceding experiment with whole wheat was under way,
`tests were made of the blacktongue-producing potency of a number
`of diets in which were included varying amounts of commercial
`wheat germ as a source of “vitamin B.”” The results of one of these
`tests which happened to be with a diet that included an unusually
`large quantity of the wheat germ, suggested rather strongly that this
`germ might possess definite blacktongue-preventive action. This
`led us to carry out the following experiment:
`
`EXPERIMENT 3
`
`26,
`
`
`
`Elysium Health Exhibit 1015
`Page 8 of 38
`
`

`

`
`
`June 8, 1928
`
`1396
`
`On August 11, 1925, at the endof a period of 77 days, presented the first signs of
`an attack of blacktongue, which ended in death during the night of August
`22-23, 1925.
`Dog 86.—Bitch. Whelpedin the laboratory October 12, 1924, On stock diet
`to April 28, 1925.
`Irom April 28 to May 26, 1925, on an experimental dict which
`included wheat germ.
`(
`May 26, 1925:
`In good condition; begins wheat-germdiet No. 197.
`On December 27, 1925, at the end of 215 days, presented a suggestive reddening
`of the mucosa of the floor of the mouth which gradually faded during the suc-
`ceeding 48 hours. Presented no other evidence of blacktongue at any time
`during a further period of observation which ended May 26, 1926.
`In good
`condition at the close of the year on the wheat-germdiet.
`Dog 87.—Bitch. Whelped in the laboratory October 12, 1924. Onstock diet
`up to April 28, 1925. From April 28 to May 26, 1925, on an experimental diet
`which included wheat germ,
`:
`May26, 1925: In good condition; beging wheat-germdiet No. 197.
`May 26, 1926: Completes one year on the wheat-germdiet.
`Is in good condi-
`tion. Has presented no recognizable evidence of blacktongue at any time dur-
`ing this feeding period.
`:
`Dog 88.—Male. Whelped in the laboratory October 12, 1924. On stock dict
`to April 28, 1925. From April 28 to May 26, 1925, o

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket