DOC TORAL D ISSERTATION SERIES TheDiseases Of New-Born lam bs With SpecialEmphasis On ftacierio- Tafhology__ ChinqJiwi Cheng TITLE DATE AUTHOR ms UNIVERSITY DEGREE JL 2 PUBLICATION NO. mi n i 7QZ 1111111 1111111 3 y UNIVERSITY MICROFILMS H A N N ARBOR ■ MICHIGAN THE DISEASES OE NEWBORN LAMBS WITH SPECIAL EMPHASIS ON BACTERIOPATHOLOG-Y C hing-tuan Cheng, T h e s is (Ph.B . ) F i f t y - f i v e newborn lambs a f f e c t e d w ith a v a r ie t y o f d is e a s e s were in c lu d e d in t h i s stu d y and th e problem was a tta c k e d h e m a to lo g ic a lly , b a c t e r i o l o g i c a l l y and p a t h o lo g ic a lly . The h e m a to lo g ic a l in v e s t ig a t io n c o n s is t e d o f stu d y in g th e b lo o d from both normal sheep and p a t h o lo g ic a l lam bs. from normal sheep served a s a c o n t r o l. The b lo o d v a lu e s o b ta in e d The r e s u l t s were b r i e f l y summarized i n th r e e t a b le s and d is c u s s e d in d e t a il i n c o n n ectio n w ith th e in d iv id u a l ca ses. The a verage b lo o d v a lu e s o f normal lambs were - red b lood c e l l s 1 0 .UUU.2S6 per cram, hem oglobin 1 0 .9 gm. p e r 100 cc» w h ite b lo o d c e l l s 7 ,9 7 9 per cmra w ith d i f f e r e n t i a l count o f 28# n e u t r o p h ils , 70# lym p h ocytes, 1$ m onocytes and 1# e o s in o p h ils , w h ile th o s e o f normal ewes were - red b lo o d c e l l s 8 , 607*000 p er cmm, hem oglobin 10. D8 gm p er 100 c c , w h ite b lo o d c e l l s 8 ,2 6 3 w ith d i f f e r e n t i a l count o f 30$ n e u t r o p h ils , 65. 25# lym p h ocytes, .^.1# m onocytes and U# e o s in o p h i ls . .. ............ ............ In th e b a c t e r i o l o c r 1 s t u d ie s , U l c u ltu r e s o f a e r o b e s and J anerobes were i s o l a t e d from v a r io u s c a s e s . By means o f m o rp h o lo g ica l, b io c h e m ic a l, and p a t h o g e n ic it y t e s t s , th e s e c u ltu r e s w ere i d e n t i f i e d and grouped under 9 g en era. They were - S ta p h y lo co ccu s, D ip lo c o c c u s, N e is s e r ia , E s c h e r ic h ia , B acterium , P a s t e u r e lla , C orynebacterium , A ctinom yces and C lo strid iu m . Two c u ltu r e s were undeterm ined. Twenty (U8 . 78# ) o f th e U l o r i g i n a l a e r o b ic c u ltu r e s w ere recovered from in o c u la te d m ic e, 13 (3 1 * 7 # ) o f which were d e f i n i t e l y v i r u le n t . R ab b its were found to b e q u ite r e s i s t a n t to th e c u ltu r e s and were not s u it a b le fo r p a t h o g e n ic it y t e s t s . As. a r e s u l t o f p a t h o lo g ic a l and b a c t e r i o l o g ic a l s t u d ie s , 15 d i f f e r e n t d is e a s e s were diagnose nam ely, w h ite m u scle d ise s-se , s ta p h y lo c o c c ic in f e d t io n , n a v e l I n f e c t io n , docking i n f e c t io n , c a s t r a t io n wound, "broncho­ pneumonia, p a s t e u r e l l o s i s , en terotoxem ia, m e n in g itis , p e r i t o n i t i s , e n t e r i t i s , g a s t r i c u lc e r a t io n and p e r f o r a tio n , d ie ta r y d e f ic ie n c y , c o n g e n ita l an o m a lies, and an undeterm ined group. Most o f th e se d is e a s e s were s tu d ie d more or l e s s in d e t a i l and a number o f c o n d itio n s such a s c o n g e n ita l i n t e r s t i t i a l broncho­ pneumonia, p a te n t ductus a r t e r io s u s , p a te n t foramen o v a le , g a s tr ic u lc e r s and p e r fo r a tio n , and en cep h alom alacia were rep o rted fo r th e f i r s t tim e. The h is to p a th o lo g y o f w h ite m uscle d is e a s e in lambs was s tu d ie d in d e ta il. The f in d in g o f m uscle g ia n t c e l l s ( s k e l e t a l and ca rd ia c) in th e c a s e s o f w h ite m uscle d is e a s e and t h e ir s ig n if i c a n c e in m yo-regen eration are co n sid ere d new to m ed ical s c ie n c e and o f v i t a l im portance in e x p la in in g th e p a t h o lo g ic a l phenomena in v o lv e d . The s p e c i f i c fu n c tio n o f th e m uscle g ia n t c e l l s and th e modes o f t h e ir fo rm a tio n were f u l l y d is c u s s e d . Their f u n c tio n i s to remove th e dead m uscle f i b e r s , and they were formed e it h e r by f u s io n or by n u c le a r p r o l i f e r a t i o n w ith ou t cy to p la sm ic d iv is io n . The c a r d ia c m uscle was observed to p o s s e s s th e c a p a c ity f o r regen era­ t i o n , and t h i s i s a ls o c o n sid e r e d new to m ed ical s c ie n c e . The n atu re and o r ig in o f the s o - c a lle d "anitschkow myocyCe" and "A schoff c e ll* 1 were f u l l y d is c u s s e d and e v id e n c e was g iv e n b ea rin g on th e p o s i t i o n o f th e s e c e l l s in th e myocardium. In s h o r t, "Anitschkow myocyte" was found to sim u la te v ery much th e r e g e n e r a tin g ca r d ia c m uscle c e l l s and th e "A schoff c e l l " th e ca r d ia c m uscle g ia n t c e l l s . The fa n c y and p e c u lia r terms such a s " rep air c lu b s o f m uscle", " m u ltin u clea ted s y n c y t ia l m asses", " large m u ltin u c le a te d p la sm a tic m asses", " s y n c y tia l sp r o u ts w ith m u ltip le n u c le i" , " cytoplasm ic syncytium w ith a la r g e number o f n u c le i" , and " m u ltin u clea ted c e l l s in m uscle" were e x p la in e d and d e s ig n a te d a s synonyms o f e it h e r s k e l e t a l or c a r d ia c m uscle g ia n t c e l l s . The n a tu r e and th e o r ig in o f th e s o - c a l l e d " m u sk elzellen sch lau ch e" o f Waldeyer was d is c u s s e d in d e t a i l . T h is term d e s ig n a te s a group o f -3 - r e g e n e r a tin g s k e le t a l m uscle c e l l s to g e th e r w ith one o r more m uscle g ia n t c e lls . The n ature and o r ig in o f the s o - c a l l e d "Aschoff body" was d iscu ssed * T his hody i s probably a mass o f r e g e n e r a tin g ca rd ia c m uscle c e l l s to g e th e r w ith one or more c a rd ia c m uscle g ia n t c e l l s . A b r i e f and c o n c is e statem ent was g iv e n con cern in g th e p a t h o lo g ic a l p r o c e s s e s in v o lv e d in m uscular d istu r b a n c e s. The p r o c e s s e s in v o lv e d are d e sig n a te d a s "myo-inflaramation and s c a r - t i s s u e rep air" fo r t is s u e r e a c t io n to s se v e re in ju r y and "m yo-degeneration and m yo-regen eration" fo r t i s s u e r e a c tio n toward a mild in ju r y . A new te c h n ic o f opening the c r a n ia l c a v it y f o r b r a in exam ination was d e sc r ib e d . T h is was done by making a f r o n t a l s e c t io n through an im aginary l i n e , p a s s in g through n a sa l c a v i t i e s , f lo o r o f o r b it s and about d h a lf an in c h above th e e a r s u n t i l i t reaches! th e o c c i p i t a l r e g io n o f th e s k u ll. Then, by g e n t le t ip p in g and w ith th e h e lp o f th e b lu n t t i p o f a p a ir o f s c i s s o r s , a g r e a te r p a r t o f th e b r a in (th e e n t ir e cerebrum) was s lip p e d out o f th e upper h a l f o f the s k u ll and exposed, le a v in g th e cereb ellu m and m edulla o b lo n g a ta in th e low er h a l f . The n a tu re o f th e v a r io u s d is e a s e s o f newborn lambs was s t r e s s e d , and s u g g e s tio n s were made f o r th e c o n tr o l o f some o f th e more im portant c o n d itio n s . THE D I S E A S E S OF FEW-BORN LAMBS A I T H S P E C I A L EMPHASIS ON 5 A C T E R I 0 - P A T H 0 L 0 G Y uj T n i n g - t u a n Cheng " '■ ' - ' ' "A TRESIS"- ' -■ ' - - '- ' 3u omit t e d t o t he G r a d u a t e S c h o o l o f Mi chi gan S t a t e C o l l e g e o f A g r i c u l t u r e a n d Ap p l i e d Scie nc e i n p a r t i a l f u l f i l m e n t of the r e q u i r e m e n t s f o r t h e d e g r e e of DOCTOR OF PHILOSOPHY D e p a r t m e n t o f Animal P a t h o l o g y 1945 CONTENTS ACKNOWLEDGEMENT I. II. III. INTRODUCTION 1 HISTORICAL REVIEW ?. EXPERIMENTAL STUDIES PA 1. M a t e r i a l s end met h o d s PA (l) Sources of m a t e r i a l s P4 (?) Methods of s t u d y P5 A. H e i n o u s fur study ing b l o o u and blood chemistry (a) (b) B. Bl o o d s t u d i e s on n o r m a l animals E5 Blood s t u d i e s on p a t h o ­ logical cases 30 B a c t e r i o l o g i c a l met h o d s (a) '- - C. ?■5 3P T e c h n i c f o r c u l t u r i n g and iso lating bacteria B a c-terrological' t e s t s ■ 3? - ; 34" a. P r e p a r a t i o n of media 34 b. Biochemical t e s t s 40 c. Pathogenicity te s ts 46 P a t h o l o g i c a l methods 5? (&) Te c h n i c u s e d f o r a u t o p s y 5? (b) Technic f o r p r e p a r i n g p a t h o ­ logical tissues " ‘ 5p 2, P r e s e n ta ti o n of cases 53 (l) H is to r y of the case 53 (P) Diagnosis (3) E t i o l o g i c a l agent (4) Elood s t u d y 0 . 0. (5) IV. V. VI. VII. Blood p i c t u r e Blood ch e m is t r y Pathological findings s. Gross l e s i o n s b. Microscopic l e s i o n s DISCUSSION OF RESULTS SUMMARY BIBLIOGRAPHY PLATES 158 . 180 183 1-30 A cknowledgem ent The a u t h o r w i s h e s t o e x p r e s s h i s s i n c e r e t h a n k s t o Dr. Frank T h o r p , J r . , u n d e r whose l o f t y inspiration, constant su p e rv is io n , a nd u n f a i l i n g i n t e r e s t s t h i s v e s t i g a t i o n was u n d e r t a k e n and t h e r e s u l t s in­ are h e r e w i t h dedicated. He i s a l s o g r e a t l y i n d e b t e d t o Dr. E. T. Ha l l ma n f o r h i s k i n d g u i d a n c e and v a l u a b l e h e l p i n c h e c k i n g t h e pathological tis s u e s . G r a t e f u l ac k n o wl e d g e me n t i s a l s o due t o Dr. R. F. Langham f o r h i s h e l p i n t a k i n g t h e p h o t o m i c r o g r a p h s and p i c t u r e s and t o Dean Ward G i l t n e r , Dro. P. W. Ts o u , H. J . R. A. R u n n e l l s , Stsfseth, L. B. S h o l l , Prof. B. J . C. L. C o l e , Ki l l har n, C. F. C l a r k , P. A. Hawk i n s , "Hr~R". ...Ruhland,- M. - Lol s. C a l h o u n , &. ■.S,,„ . . Feenst r a, ' 'J..' H.,. Timer,-. Mr, Har ry C r a n d e l l , Jr., s u g g e s t i o n s and a s s i s t a n c e and o t h e r s f o r t h e i r h e l p f u l i n one way o r a n o t h e r . The w r i t e r d e e p l y a p p r e c i a t e s t h e f i n a n c i a l s u p p o r t o f t h e China F o u n d a t i o n and t h e s c h o l a r s h i p p r o v i d e d by Mi chi gan S t a t e C o l l e g e f o r t h e p a s t few y e a r s wh i c h made it p o s s i b l e f o r him t o c o m p l e t e t h i s i n v e s t i g a t i o n . -1- The d i s e a s e s o f n e w - b o r n l ambs w i t h s p e c i a l emphas i s on b s c t e r i o - p a t h o l o g y C h i n g - t u s n Cheng I• Formerly, Introduction i n t h i s c o u n t r y as e l s e w h e r e , most l ambs wer e bo r n i n May on g r a s s and p r a c t i c a l l y f ew, i f wer e e n c o u n t e r e d . ( s o - c e l l e d " g r a s s - l a m b i n g 11) any, Under t h e p r e s e n t c o n d i t i o n o f m a r k e t ­ i n g l ambs e a r l y i n t h e f a l l , early d i s e a s e s of the new-born 11s h e d - l a m b i n g " s p r i n g h a s been p r a c t i c e d . during the O f t e n as a r e s u l t o f i n c l e m e n t w e a t h e r , u n s u i t a b l e c o n d i t i o n s and u n s a n i t a r y surr oundings i n th e sheds t o g e t h e r w i t h overcrowding, the d i s e a s e s of n e w - b o r n l a mb s ha ve i n c r e a s e d snd e x t e n s i v e l o s s e s e ach y e a r a r e r e p o r t e d by f a r m e r s , and v e t e r i n a r i a n s . e x t e n s i o n men, Under t h i s t ype o f management, a number o f i n t e r e s t i n g d i s e a s e s i n n e w - b o r n l ambs a r e e n c o u n t e r e d a n d u n f o r t u n a t e l y n o t much d e t a i l e d work h a s b e e n done i n t h i s p a r t i c u l a r f i e l d . In order to g e t a b e t t e r u n d e r s t a n d i n g o f t h e s e d i s e a s e s so as t o f or m a. sound b a s i s f o r diagnosis, treatment, and c o n t r o l , the p r e s e n t i n v e s t i g a t i o n has been un d e rta k e n sin ce e a r l y s p r i n g of 1944 and t h e r e s u l t s a r e h e r e w i t h p r e s e n t e d . I I . H i s t o r i c a l r e v ie w For a h i s t o r i c a l r e v i e w o f t he d i s e a s e s o f n e w - b o r n l a mb s , i t seemed a d v i s a b l e to divide th e l i t e r a t u r e s e p a r a t e c a t e g o r i e s so t h a t a clearer and b e t t e r i d e a c o n c e r n i n g i n d i v i d u a l d i s e a s e s mi ght be o b t a i n e d . f o l l o w i n g c a t e g o r i e s s uch a s : in general, arthritis, white-muscle d is e a s e , i l . . l> . l i t : “I -i 4- i i ^ 4* v-> ^ u CJ- c . u u i c •-«»* >?-4- ± u c* o The d i s e a s e s o f n e w - o o r n lambs enteritis, enterotoxemia, pneumoni a, and m i s c e l l a n e o u s d i s e a s e s wer e Under each c a t e g o r y , followed. into vv ^ n v i r. ri o ppc; m i p u a c h r o n o l o g i c a l o r d e r of rJs uux t-s n la p , p o .o -P 4 "F + u± ± ± u j j u ru o w i l l be o b s e r v e d . 1 • D i s e a s e s o f n e w- b o r n l a mb s i n g e n e r a l In 1902, C r a i g and Bi t t i n g * ' * ' were p r o b a b l y t h e f i r s t in t h i s c o u n t r y t o pay some a t t e n t i o n t o t h e d i s e a s e s of sheep. They d i s c u s s e d s uch d i s e a s e s a s w h i t e l a mb s , p e r i t o n i t i s , e n c e p h a l i t i s , .... and'" a r t h r i t i s . ’ ' G a l l a g h e r 1s ’" scours of cerebrospinal meningitis, """" "................ ” f i r s t work on " D i s e a s e s of Sheep" a p p e a r ­ ed i n 1921 and i t was r e v i s e d l a t e r 1 by S c h o e n i n g i n 1933. In t h i s b u l l e t i n , a number of d i s e a s e s r e l a t e d t o y o u n g l ambs wer e d i s c u s s e d among whi ch we r e : white scours, n e c r o c a c i l l o s i s of navels, joint i l l , p erito n itis, and m e n i n g i t i s . b e l i e v e d t h a t Act i n o m y c e s n e c r o p n o r u s was They the e t i o l o g i c a l a g e n t of n e c r o b a c i l l o s i s , b a c t e r i a or p a r a s i t e s t h e c a u s e s of m e n i n g i t i s , white scours. o f t e n seen i n and Bact e r i u m c o l i communi s t h e c a u s e of They a l s o m e n t i o n e d t h a t m e n i n g i t i s was more l a mos t h a n i n o l d e r s h e e p . -3 - J u n g n e r r end Welch 46 d i s e a s e s from Montana. 7 Of t h e lamb d i s e a s e s b r o u g h t t o th e ir attention that year, dysentery. cocci die sis , i n 1927, r e p o r t e d on lamb The o t h e r t h r e e t h e most i m p o r t a n t by f a r was diseases—umbilical infection, and t h e b r a d s o t - l i k e d i s e a s e —wer e a l s o i n c l u d ­ ed but were c o n s i d e r e d t o be o f l e s s e r i m p o r t a n c e . They f e l t t h a t t he c o c c i die. must be r e g a r d e d as p o s s i b l y p a t h o g e n i c f a c t o r s i n " s t i f f lambs" and t h e w h i t e mus cl e l e s i o n s o f a. d e g e n e r a t i v e n a t u r e wer e p r o b a b l y s e c o n d a r y i n n a t u r e . Vi b r i o n s e p t i d u e was t h o u g h t t o be the' e t i o l o g y o f t h e bradsot-like disease. In 1929, b a k e r ’s book on "Sheep D i s e a s e s " was p u b l i s h e d . ( 2nd e d . ) In the s e c t i o n d e a l i n g w i t h the d i s e a s e s of y oung l ambs, he m e n t i o n e d t h e f o l l o w i n g c o n d i t i o n s : t a l defects 4 (imperforate anus, hernia, hemorrhage, s u f f o c a t i o n ) , congeni­ skin drying, um bilical p i n n i n g ( r e t e n t i o n o f t h e meconi um), •'•v- - -navei-i-H-j, w hite- scours*; - go-i-ter~,~ corntrpationy'-etc-^''' -A b r ie f a c c o u n t of each d i s e a s e d c o n d i t i o n a s t o i t s c a u s e , symptoms, end t r e a t m e n t was g i v e n . Mar sh ( 1929) 59 m e n t i o n e d t h e c o n d i t i o n of " s t i f f l ambs" as one of t n e s e v e r a l o b s c u r e d i s e a s e s . A c c o r d i n g t o him, a t l e a s t , t h r e e s e p a r a t e d i s e a s e s were o r d i n a r i l y r e g a r d e d u n d e r t h e g e n e r a l name " s t i f f l a m b s " , and t h e y were u m b i l i c a l infection, s t i f f l a mb s , a n d w h i t e - m u s c l e Two y e a r s l a t e r disease. " 65 ( 1 9 3 1 ) , Mi e s s n e r & Koser ^ r e p o r t e d on lamb d i s e a s e s i n Germany: "About h a l f o f a l l e xa mi n e d l ambs showed a s p e c i f i c i n f e c t i o n and, o f t h e s e , i n f e c t i o u s -4 pneumoni a (B. b i p o l e r e o vi s e p t i c a u m ) was t h e most p r e v a l e n t ( 4 3 fo). Ot h e r o r g a n i s m s i s o l a t e d f rom c a s e s of pneumonia, wer e B. p yo g e n e s , Streptococci, and t h e b a c i l l u s of Dar nmann-Fr eese. B. Ooli was r a t h e r common (23fo) w h i l e a n a e r o b e s wer e f o u n d t o a lesser extent. Some o f t h e n o n - o a c t e r i a l d i s e a s e s were ascribed to d i e t e t i c e r r o r s . " I n t h e same y e a r ( 1 9 3 1 ) , M i l l s gave a b r i e f a c c o u n t o f t h e f o l l o w i n g lamb d i s e a s e s , ing the nature and a d v i c e a s t o t h e t r e a t m e n t : 66 describ­ white scours, B. n e c r o p h o r u s i n f e c t i o n , and s p o t t e d l i v e r d i s e a s e . ' gQ I n 1 932, M a r s h ' s a r t i c l e on " P r e v e n t i o n of D i s e a s e s i n Young Lamos" was - p u b l i s h e d . The a u t h o r d e a l t w i t h t h i s s ub ­ j e c t under t h r e e c a t e g o r i e s , n a me l y , d i s e a s e s due t o manage­ ment of t h e ewe d u r i n g p r e g n a n c y , i n f e c t i o u s d i s e a s e s (necro-bacillosis, arthritis, miscellaneous d ise a se s . dysentery, pneumoni a. ) , Under t h e l a s t c a t e g o r y , and he s p e c i ­ f i c a l l y d i s c u s s e d s t i f f - l a m b s or w h ite-m u scle d i s e a s e . The w-h-i t-e- appearance-...- 0 'f -.the- a f f ec.te-d...groups, of. .muscle ..f...i b a r s was due t o a d e p o s i t of t r i c a l c i u m p h o s p h a t e , and t h e d i s e a s e d c o n d i t i o n was b r o u g h t a b o u t by a d i s t u r b a n c e of n o r m a l c a l c i u m and p h o s p h o r u s b a l a n c e . T u r n e r " ^ i n 1932, r e p o r t e d a r a t h e r l e n g t h y a r t i c l e on " F i e l d and. E x p e r i m e n t a l S t u d i e s of Sheep D i s e a s e s " . considered j o i n t - i l l ( p ye mi c a r t h r i t i s ) He o f l ambs a s a r e s u l t of n a v e l i n f e c t i o n , g o i t e r a s i o d i n e d e f i c i e n c y , and s c o u r s as b a c t e r i a l i n f e c t i o n , Howerth ( 1 9 3 4 ) ' published a b rie f i n g d i s e a s e s o f l a mb s : navel i l l , a c c o u n t on t h e f o l l o w ­ dysentery, p n e u mo n i a , . -5 - hemorrhagic s e p t i c e m i a (P a s t e u r e l l a o v i s e p t i c u s ), arthritis, and w h i t e - m u s c l e d i s e a s e . poly­ Only g r o s s l e s i o n s w e r e d e s c r i b e d f o r t h e v?hite mu s c l e d i s e a s e . In 1936 , Oppermann on d e s c r i b e d two mein d i s e a s e d c o n d i ­ t i o n s f ound i n t h e l a m b i n g p e n , n a m e l y , and h e m o r r h a g i c s e p t i c e m i a o f l ambs. the p a r a l y t i c d i s e a s e The f o r m e r was c o n s i d e r ­ ed t o be c a u s e d by n a v e l i n f e c t i o n and n u t r i t i o n a l disturbance, w h i l e t h e l a t t e r was c a u s e d by P a s t e u r e l l a b a c t e r i a w i t h d u s t y hay ana l i t t e r as the p r e d i s p o s i n g f a c t o r s . 70 The Mon ban a. S t a t i o n w o r k e r s ( 1937) p u b l i s h e d a summary of p r a c t i c a l i n f o r m a t i o n d e a l i n g w i t h s h e d s a n i t a t i o n , of p r e g n a n t e w e s , n e c r o b a c i l l o s i s of t h e l i v e r , disease, p araly sis, t e r y , p neumoni a, dirty joint e a t i n g , w o o l - e a t i n g , lamb d y s e n ­ sore eyes, Two y e a r s l a t e r care s t i f f lambs, (1939), and b l a c k l e g . t h e Oregon S t a t i o n 78 published a p r e l i m i n a r y r e p o r t d e a l i n g w i t h t h e c a u s e of f o u r r a n g e d i s e a s e s o f s h e e p , such a s l u n g e r d i s e a s e , dysentery, s t i f f - l a m b s / lamb and p r e g n a n c y d i s e a s e , b u t no d e f i n i t e conclusions wer e made. I n 1949, Dykstra e t a l ?3 stated that " c o n t r o l of sheep d i s e a s e s i s e s s e n t i a l l y s p r o b l e m of p r e v e n t i o n r a t h e r t h a n of t r e a t m e n t " . I n d e a l i n g w i t h d i s e a s e s o f y ou ng l a m b s , a s p e c i a l d i s c u s s i o n was g i v e n t o e ach o f t h e f o l l o w i n g , namely, s a n i t a t i o n at la m bi n g, s c o u r s , i n d o c k i n g and c a s t r a t i n g , cleanliness m a l i g n a n t edema, p o l y a r t h r i t i s , s t i f f lamb d i s e a s e , n a v e l i l l , the idea t h a t blackleg, "polyarthritis etc. However, t h e a u t h o r s h a d and s t i f f lamb d i s e a s e were somet i me c l a s s e d as t h e same d i s e a s e , b e c a u s e t h e y c a u s e i n f l a m m a t i o n of t h e j o i n t s " I n t h e same y e a r ( 1 9 4 2 ) , an a r t i c l e e n t i t l e d " P r e v e n t i n g 98 Lamb L o s s e s " was p r e p a r e d by Thor p . In t h i s a r t i c l e , the i m p o r t a n c e and means of p r e v e n t i n g l o s s e s of l ambs from d i s e a s e s were c o n s i d e r e d . saying: The a u t h o r e x p r e s s e d h i s i d e a by " I t h a s been e s t i m a t e d t h a t m a r k e t i n g o n l y 4 / 5 of a Iamb c r o p means no p r o f i t for the farm er. At l e a s t 3/4 of t h i s l o s s o c c u r s d u r i n g t h e f i r s t p o r t i o n o f t h e l a m b ' s life and i s l a r g e l y p r e v e n t a b l e . " Ni ne d i f f e r e n t d i s e a s e d c o n d i t i o n s s u c h as n a v e l i n f e c t i o n , pneumoni a, " s t i f f lambs", etc. s c o u r s or d y s e n t e r y , , were m e n t i o n e d and met hods o f c o n t r o l we r e d i s c u s s e d . Last y e a r (1944), t h e N a tio n a l V e te r in a ry A s s o c i a t i o n 35 o f G r e a t - B r i t a i n and I r e l a n d made a r e p o r t i n w h i c h some d i s e a s e s o f n e w - o o r n l a mb s wer e i n c l u d e d . me nt i r e d w e r e : kidney d isea se lamb d y s e n t e r y (£1 . w e l c h i i , aureus) , j o i n t - i l l (Cl. w e l c h i i , Type B), pul py Type D ) , pyemi a ( S t a p h y l o c o c c u s ( S t r e p t o c o c c u s of L a n c e f i e l d ' s g r o u p C . ) , Erysipelothrix infection, tion. Among t h o s e and F u s i f o r m i s n e c r o p h o r u s i n f e c ­ A b r i e f a c c o u n t of t h e n a t u r e o f t h e d i s e a s e , i t s diagnosis, s ympt oms, p a t h o l o g y , t r e a t m e n t , and c o n t r o l was g i v e n f o r most of t h e s e c o n d i t i o n s . P. Arth r i t i s stiff (polyarthritis, lambs, n a v e l - i l l , joint-ill, lameness, erysipelothrix infection) A number o f d i f f e r e n t t e r m s have been u s e d t o d e s i g n a t e i n f l a m m a t i o n o f j o i n t s r e s u l t i n g from i n f e c t i o n s u c h a s : arthritis, polyarthritis, joint-ill, navel-ill, lameness, -7" s t i f f - l a m b s " , and e r y s i p e l o t h r i x i n f e c t i o n . Some o f t h e s e t e r m s a r e v e r y m i s l e a d i n g and c a u s e a l o t o f c o n f u s i o n . For t h e sake o f u n i f o r m i t y , t h e t e r m " a r t h r i t i s " i s r e - e m p h a s i z e d and u s e d h e r e . From t h e l i t e r a t u r e , it i s a p p a r e n t t h a t two f o r ms o f a r t h r i t i s have been e n c o u n t e r e d i n l a m b s , n a me l y , t h e a c u t e and c h r o n i c f o r m s . The a c u t e form i s n o n - s p e c i f i c and i s a s s o c i a t e d w i t h p y o g e n i c o r g a n i s m s w h i l e t h e c h r o n i c one i s s p e c i f i c and a s s o c i a t e d w i t h E r y s i p e l o t h r i x r h u s i o p a t h i a e . 20 In 1925, C o r n e l l and G l o v e r r e p o r t e d cases of a r t h r i t i s due e i t h e r t o s t r e p t o c o c c i o r swi ne e r y s i p e l a s . I t was s t a t e d t h a t more o u t b r e a k s were f o u n d t o be c a u s e d by s t r e p t o c o c c i . On t h e o t h e r h a n d , swi ne e r y s i p e l a s was r e s p o n s i b l e f o r onl y one o u t b r e a k d u r i n g t h e p e r i o d of t h e i r i n v e s t i g a t i o n . 83 Seddon ("192S) made a g e n e r a l r e v i e w on t h e s u b j e c t o f " l a me n e s s i n l a m b s " , and he p o i n t e d o u t t h a t s e v e r a l Qu i t e d i s t i n c t a f f e c t i o n s of lambs, d i f f e r e n t i n c a u s e , i n symp­ t o ms , and i n age o f a n i m a l s a f f e c t e d , wer e i n c l u d e d under t he t erm " l a m e n e s s " . Two y e a r s l a t e r (1931) , t h e Mont ana S t a t i o n 68 invest­ i g a t e d t h e same pr obl em i n l ambs from two weeks t o s e v e r a l mont hs of a g e . The c a u s e of t h i s d i s e a s e was shown t o be an i n f e c t i o n o f a s p e c i f i c b a c i l l u s which gai n ed e n t r a n c e to t h e body t h r o u g h t h e n a v e l c o r d a t b i r t h , d o c k i n g wound. or t h r o u g h t h e L o s s from t n i s c a u s e c o u l d be p r e v e n t e d by d i s i n f e c t in g the navel at b i r t h w i t h t i n c t u r e o f i o d i n e and by p r o p e r d o c k i n g t e c h n i c u s i n g a h o t i r o n . T h i s same i n f o r m a t i o n was l a t e r p u b l i s h e d f r om t h e same S t a t i o n i n RQ t h e same y e a r , while th e e t i o l o g i c a l ag en t , (swine , e r y s i p e l a s ) was i d e n t i f i e d and r e p o r t e d s i r y e a r s l a t e r (1937) ' . The De p a r t me n t of A g r i c u l t u r e of hew Sout h Wa l e s (1931) 7? f ound two f or ms of a r t h r i t i s i n l ambs and young s h e e p , namel y, a n o n - s u p p u r e t i v e s p e c i f i c i n f e c t i o n (E. r h u s i o p a t h i a e and 8 n o n - s p e c i f i c t ype a s s o c i a t e d w i t h p y o g e n i c o r g a n i s m s (B. p y o g e n e s ) . I n 1933, Howarth 43 d e s c r i b e d c a s e s of p o l y a r t h r i t i s whi ch a p p e a r e d i n lambs a f t e r d o c k i n g and c a s t r a t i n g . A s t r a i n of E. r h u s i o p a t h i a e was f o un d t o be t h e c a u s a l a g e n t . , ^ 89 In t h e same y e a r ( 1 9 3 3 ) , Seddon wor ked w i t h a s p e c i f i c a r t h r i t i s i n s h e e p which was d e f i n e d a s a s y n o v i t i s and o s t e o ­ a r t h r i t i s due t o a s p e c i f i c and m a n i f e s t e d by l a m e n e s s . Dacillus ( r e s e m b l i n g B. pyog e n e s ) , I t a f f e c t e d s h e e p from f o u r weeks ,.to-«. s e v e n t e e n -mantJxs- of - age- . • ^Attempts... t o-d:re-at ""the' - c o n d i t i o n failed. Blakemore^ described a disease 1939. o f l ambs i n Thi s d i s e a s e was c h a r a c t e r i s e d by l a m e n e s s , r a p i d emaciation, sheath, (joint-ill) s u p p u r a t i o n of j o i n t s , s y n o v i a l b u r s a l and t e n d o n out o t h e r pyemic c h a n g e s were v e r y r a r e l y o b s e r v e d . A non-hemolytic s trep to co ccu s , anti g en ic a lly r e l a t e d to L a n c e f i e l d ' s Group C was i s o l a t e d f rom t h e a f f e c t e d lambs and t h e d i s e a s e was e x p e r i m e n t a l l y r e p r o d u c e d . The a f f e c t e d l ambs were t r e a t e d w i t h s e v e r a l d a i l y d o s e s of 1 . 5 grams o f s u l f a n i l a m i d e and t h e r e s u l t s were v e r y s a t i s f a c t o r y . 3. E n t e r i t i s Only two r e f e r e n c e s h a v e be e n n o t i c e d i n c o n n e c t i o n with th is d i s e a s e , end b o t h h a p p e n e d t o be p u b l i s h e d i n t h e same y e a r ( 1 9 3 3 ) . However , t h e e n t i t y o f t h e s e c a s e s i s doubtful. Car3 17 r e p o r t e d t h a t l a mb s 14- 30 d a y s old. s u f f e r e d from 8 d i s e a s e i n whi ch t h e a f f e c t e d l ambs showed s t i f f n e s s w i t h muscl e i n f l a m m a t i o n and d e g e n e r a t i o n . These l a m e s , when f e d on m i l k , r e c o v e r e d c o m p l e t e l y i n 2 - 3 d a y s . fciti upiuu"t 6 u t h e c a u s e ot He o h i s uon&i oiou uo uiic iugfcisuion 01 c o a r s e f ood u n s u i t a b l e f o r a young lamb and e n t e r i t i s r e s u l t e d . I J u d g i n g .from t h i s r e p o r t , Car e mi g h t h a v e been d e a l i n g w i t h a c a s e of w h i t e - m u s c l e d i s e a s e . Heller 39 f o u n d c a s e s of i n f e c t i o u s e n t e r i t i s o f young l ambs i n C a l i f o r n i a . he mentioned t h a t t h e e n t e r o t o x e m ia type of i n f e c t i o n , " i t a p p e a r s t o be o f a s i t can r e g u l a r l y " be t h e n W n i t T e d ‘' ljy ' o r a l a d m i n i s t r a t i o n oi T i i T e r e d i n t e s t i n a l contents". However , t h e a u t h o r c o n s i d e r e d t h a t improbable t h a t an a n a e r o b e c a u s e s t h e d i s e a s e " , b e c a u s e he was u n a b l e t o i s o l a t e colon b a c i l l i " i t i s highly from s u c h c a s e s any b a c t e r i a o t h e r t h a n wh i c h woul d p r o d u c e a p o i s o n c a p a b l e o f p r o ­ ducing i n f e c t i o u s e n t e r i t i s . 4. E n t e r o t o x e mi a ( P u l p y k i d n e y d i s e a s e , bradsot-like disease, etc.) Thi s d i s e a s e h a s oeen i n v e s t i g a t e d by q u i t e a number o f r e s e a r c h w o r k e r s and r e f e r e n c e s wer e r e c e n t l y c o l l e c t e d by t h e w r i t e r . In t n i s a r t i c l e , h o w e v e r , more i m p o r t a n t wor ks a r e p r e s e n t e d . onl y some o f t he i n v e s t i g a t i o n s c a r r i e d o u t upon t h e e t i o l o g y o f i n f e c t i o u s enterotoxemia in A u s t r a lia , and i t was f o u n d t h a t t h e c a u s a l o r gan i s m was a new s p e c i e s of a n a e r o b e c l o s e l y r e l a t e d t o Cl , w e l c h i i , t h e lamb d y s e n t e r y b a c i l l u s , I n t e s t i n a l s t a s i s was t h o u g h t t o be t h e and C l , paludis. predisposing factor whi c h e n a b l e d t h e o r g a n i s m t o p r o l i f e r a t e i n t h e i n t e s t i n e and pr oduce an e x o t o x i n . A c t i v e i m m u n i z a t i o n was r e p o r t e d to give promising r e s u l t s . Four y e a r s l a t e r ( 1 9 3 6 ) , Bought on and Ha r d y 1 1 r e p o r t e d o u t b r e a k s of t h e d i s e a s e i n Texas. i d e n t i f i e d as Cl_, w e l c h i i Type D. The c a u s a l o r g a n i s m was T h i s was t h e f i r s t time t h a t t h e Cl . w e l c h i i Type D e n t e r o t o x e m i a was r e p o r t e d i n t h i s country. 74 Newsom and Thorp , i n 1938, were a b l e t o d e m o n s t r a t e t h a t 4-5fo i n t e s t i n a l f i l t r a t e s from 956 l ambs dead o f o v e r ­ e a t i n g were shown t o be t o x i c f o r l a b o r a t o r y a n i m a l s , and 19 o u t of 90 o f t h e f i l t r a t e s pr oved f a t a l t o s h e e p when i n j e c t e d i n amo u n t s v a r y i n g from 5 t o 50 c c . H e a t i n g t he o f i l t r a t e s t o 60 C. f o r 30 m i n u t e s r e n d e r e d them a t o x i c . The t o x i n was n e u t r a l i z e d , oy a n t i s e r a made from C l . w e l c h i i Types B and D, b u t n o t by Types A and C. that They c o n c l u d e d "whi l e o v e r e a t i n g seems t o d i f f e r f r om e n t e r o t o x e m i a on t h e b a s i s o f symptoms end. l e s i o n s , t e n t s of l ambs dead of t h e substances th a t t h e i n t e s t i n a l con­ two d i s e a s e s c o n t a i n t o x i c seem t o be i d e n t i c a l " . 84 In t h e same y e a r ( 1 9 3 8 ) , R o b e r t s d e s c r i b e d a s i mp l e -1 1met hod by wh i c h s h e e p c o u l d be made t o succumb t o e n t e r o ­ t o x e m i a by i n g e s t i o n of t h e c a u s a l o r g a n i s m . He empl oyed b o t h i n v i t r o and i n v i v o e x p e r i m e n t s by u s i n g a d e f i n i t e amount of Cl . w e l c h i i Type D and a v a r y i n g amount o f m i l k , and was a b l e t o p r o d u c e t h e d i s e a s e a t w i l l . In c o n c l u s io n , he p o i n t e d o u t t h a t t h e l a r g e amount o f c a s e i n p r e s e n t a f t e r i n g e s t i o n o f l a r g e q u a n t i t i e s of mi l k w o u l d r e d u c e t h e a c i d o f t he abomasum f o r a s u f f i c i e n t l e n g t h o f time t o a l l o w C l . w e l c h i i Type D t o p r o p a g a t e and p r o d u c e enough t o x i n t o cause the d i s e a s e . For t h e same r e a s o n , a. lamb t h a t i n g e s t e d a s m a l l amount 01 mi l k wou l d have l e s s c a s e i n so t h a t t h e f r e e a c i d o f t h e abomasum woul d i n h i b i t t h e b a c t e r i a l g r owt h and c o n s e o u e n t l y no d i s e a s e woul d o c c u r . The n e x t y e a r ( 1 9 3 4 ) , Shaw, Muth, and S e g h e t t i 90 report­ ed on t h e o c c u r r e n c e of " p u l p y k i d n e y " d i s e a s e i n Oregon and C l . p e r f r i n g e n s Type D was f o u n d t o be t h e c a u s e . Methods of p r e v e n t i o n b y t h e u s e o f a n t i t o x i n s wer e t r i e d and p r ov e d ’s u c c e s s f u l . Bought on & Hardy IS , i n 1941 , gave a g e n e r a l a c c o u n t of t h e d i s e a s e as i t o c c u r r e d i n lambs and k i d s o f Texas and t h e y s t r e s s e d as c o n t r o l measures e i t h e r p as siv e immunization of s u s c e p t i b l e animals or removal t o roug h, h i l l y and s p a r s e g r a s s p as tu r e t o g e t h e r with penning t h e animals o v e r n i g h t i n a dry l o t . I n t he same y e a r ( 1 9 4 1 ) , 7cj Oregon S t a t i o n w o r k e r s " able to i s o l a t e eleven d i f f e r e n t s t r a i n s of th e organism responsible for " pu l p y Ki d n ey" d i s e a s e . were f ound t o be p o t e n t t o x i n p r o d u c e r s . Al l t h e s t r a i n s were -1214 Last y e a r ( 1 9 4 4 ) , B r i t t o n and Cameron made a r e p o r t of t e n o u t b r e a k s of s o - c a l l e d e n t e r o t o x e m i a i n C a l i f o r n i a , and t h e y f e l t t h a t " t he t h e o r y t h a t i t of t h e t o x i n o f Cl . w e l c h i i i s due t o a b s o r p t i o n Type D i s i n a d e q u a t e " . They apparently believed th a t the chief e t i o l o g i c a l f a c t o r in t h e s e o u t b r e a k s was t h e q u a n t i t y and q u a l i t y o f t h e r a t i o n and t h e mechani sm i n f a t a l c a s e s a p p e a r e d s i m i l a r t o t h a t o p e r a t i n g i n " i n h i b i t o r y i l e u s " of human b e i n g s . They c a r r i e d on some e x p e r i m e n t s s i n c e l a s t y e a r i n o r d e r t o s u b s ta n tia te t h i s theory. The r e s u l t s we r e p u b l i s h e d t h i s lb year and i n summary, t h e y c l a i m e d t h a t s o - c a l l e d e n t e r o ­ t o x e m i a was a form of a c u t e i n d i g e s t i o n r e s u l t i n g from primary i n t e s t i n a l atony. 6 - Pneumonia ( b r o n c h o p n e u mo n i a , l a i k i p i s lung d isease, p l e u r o p n e u m o n i a.,) In 1993, 95 Spr ay' ' made a b a c t e r i o l o g i c a l s t u d y of pneumoni a i n sheep.,. .Two t y p e s of pneumonia.. jyere.. .st udied,* — n a me l y , a r a t h e r edemat ous t y p e f r e q u e n t l y o b s e r v e d in s p r i n g l ambs and a p u r u l e n t c h r o n i c t y p e f ou nd i n o l d e r s h e e p . He i s o l a t e d P a s t e u r e l l a o v i s e p t i c u m , a g r a m - p o s i t i v e diploeoccus, and a g r a m - n e g a t i v e d i p l o c o c c u s . were found h i g h l y p a t h o g e n i c f o r m i c e , The P a s t e u r e l l a e guinea p i g s , and rabbits. „ 4 .4 . Mettam 63 , i n 1930, d e s c r i b e d a d i s e a s e known a s " l a i k i p i a l u n g d i s e a s e " i n s h e e p and l a mbs. is a pleuro-pneumonia. In f a c t , t h i s c o n d i t i o n T h i s d i s e a s e r a n an a c u t e c o u r s e i n l ambs and y e a r l i n g s b u t was g e n e r a l l y c h r o n i c i n a d u l t s . - -13- C e r t a i n c o m p l i c a t i o n s s u c h as a c u t e a r t h r i t i s , l e s i o n s i n t h e mout h, necrotis and a c u t e o p h t h a l m i a were a l s o f o u n d . The c a u s a l o r g a n i s m mas a p l e o m o r p h i c g r a m - n e g a t i v e c o c c o b a c i l l u s whi ch was p a t h o g e n i c f o r t h e g u i n e a p i g s , r a b b i t , goat, sheep, and c a t t l e , Two y e a r s l a t e r but not f o r p i g eo n s. (193P), D e l p y ^ r e p o r t e d c a s e s o f pneumo­ e n t e r i t i s i n s h e e p from P e r s i a . A c c o r d i n g t o t h e p o s t - mo r t e m l e s i o n s t h r e e c l i n i c a l t y p e s were d e s c r i b e d , n a m e l y , pneumonic t y p e , a a t ype c h a r a c t e r i z e d by i n t e s t i n a l c o n g e s t i o n , and a t h i r d t y p e whi ch p r e s e n t e d l e s i o n s s i m i l a r t o h e m o r r h a g i c septicemia. Two o r g a n i s m s , a P a s t e u r e l l a and an u n d e t e r m i n e d g r a m - n e g a t i v e r o d , were i s o l a t e d from s uch c a s e s . An immune serum was p r e p a r e d from s h e e p and a f o r m a l i z e d b a c t e r i n was p r e p a r e d and e a c h p r o v e d s a t i s f a c t o r y . I n 1939, Ko s h e l e v 49 made i n v e s t i g a t i o n s on t h e e t i o l o g y of pneumonia i n s h e e p and l a mb s i n t h e Cr i mea, R u s s i a . - The ■- - c l i n i c a l , •pos t - r a o nt e m -f-in d in g s / a n d : a t i ol ogy* o f ‘ t h e - d i s e a s e * ' ' were d i s c u s s e d . V a r i o u s b a c t e r i a s u ch as B a c t e r i u m c o l i , S a l m o n e l l a p a r a t y p h i , Pseudomonas p y o g e n e s , and v a r i o u s c o c c i were i s o l a t e d from t h e c a r c a s s e s of 77 l a mbs and 5 s h e e p , b u t t h e y wer e a l l c o n s i d e r e d s e c o n d a r y i n v a d e r s . E x p e r i m e n t a l t r a n s m i s s i o n i n l a b o r a t o r y a n i m a l s and lambs failed. S p e c i f i c t r e a t m e n t w i t h v a r i o u s s e r a was o f l i t t l e v a l u e b ut t h e i mpr ovement o f h y g i e n i c c o n d i t i o n was con­ s i d e r e d t o be e f f e c t i v e . Besides t h e s e s p e c i a l r e f e r e n c e s , pneumoni a of lambs 11 65 was a l s o r e p o r t e d or c o n s i d e r e d by M i e s s n e r and Ko s e r -14 70 Mar s h60, H o w a r t h 4? , V e t e r i n a r y R e s e a r c h L a b o r a t o r y , Montana , Q Q end Thorp . These r e f e r e n c e s were p r e v i o u s l y m e n t i o n e d i n this article. 6 . W h i t e Muscle d i s e a s e ( " s t i f f - l a m b " d i s e a s e ) Whi te m u s c l e d i s e a s e or s o - c a l l e d " s t i f f-lamb" di sea se 64 was f i r s t r e p o r t e d and d e s c r i b e d by M e t z g e r and Hagan in 19?7 from hew Yor k . I t a f f e c t e d l ambs f r om two t o e i g h t weeks of age and was m a n i f e s t e d c h i e f l y by a d i s t u r b a n c e o f l o c o m o t i o n t h a t u s u a l l y became wor s e u n t i l e i t h e r t h e I . ... j _ . a. n v -. a i u u i a i s u i e u o r wex'e uebt i*u y e a uy j-b . uuc _ - I - ______________ — u m icr, m u _ _____ i u c *juu— d i t i o n was due t o m u s c u l a r c h a n g e s , t h e c a u s e o f wh i c h was not discovered, an i n f e c t i o n . a l t h o u g h a p p a r e n t l y i t was n o t t h e r e s u l t o f The l e s i o n s o f t h e s k e l e t a l mus cl e and h e a r t were b r i e f l y d e s c r i b e d b o t h m a c r o s c o p i c s l l y as w h i t i s h p a t c h e s and m i c r o s c o p i c a l l y as d e g e n e r a t i v e and n o t i n ­ f l a mma t o r y i n n a t u r e . The r e was p r a c t i c a l l y no c e l l I n f i'l't r h ti o n byt;'pblymorphohucIear"‘?)r!hither w anderingfreTls However, an o c c a s i o n a l p h a g o c y t i c c e l l was o b s e r v e d . I n t h e same y e a r ( 1 9 2 7 ) , Montana by J u n g h e r r and Welch t h i s d i s e a s e was r e p o r t e d from 4--o but i t was r e g a r d e d as secondary to c o c c i d i o s i s . Two y e a r s l a t e r ( 1 9 2 9 ) , Welch, Ma r s h, and T u n n i c l i f f r e p o r t e d t h i s d i s e a s e a g a i n i n Montana. 103 Tne d i s e a s e o c c u r r e d l a r g e l y i n l ambs c o n f i n e d t o s m a l l pen s and s hed d u r i n g t h e f i r s t two o r t h r e e weeks o f t h e i r l i f e , u n u s u a l amount o f e x e r c i s e f o l l o w e d by an on p a s t u r e . * 77 The f o l l o w i n g y e a r ( 1 9 3 0 ) , i t was r e p o r t e d f r om Oregon -1 5 A c h e m i c a l a n a l y s i s o f t h e w h i t e m u s c l e from l ambs was made and about 0 . 9 p e r c e n t o f c a l c i u m was f o u n d as co mp ar ed t o 0 .1 2 p e r c e n t c a l c i u m i n t h e no r ma l m u s c l e of t h e a n i m a l s . I n t h e same y e a r , w o r k e r s a t New York ( C o r n e l l ) Station were a.ole t o p r o d u c e t h e d i s e a s e e x p e r i m e n t a l l y by f e e d i n g t h e p r e g n a n t ewes w i t h h i g h - p r o t e i n g r a i n r a t i o n p l u s a l f a l f a hay c o mb i n e d w i t h l i m i t e d e x e r c i s e . 58 In 1931, Heath' ' r e p o r t e d on t h e o c c u r r e n c e o f " s t i f f d i s e a s e 11 o f l a m b s i n A l b e r t a , fast bacillus. Canada, and i s o l a t e d an a c i d - I t woul d seem t h a t H e a t h ' s work was n o t done on a t r u e c a s e o f w h i t e - m u s c l e d i s e a s e . The Mont ana 88 A g r i c u l t u r a l E x p e r i m e n t a l S t a t i o n ( 1931) c a r r i e d on an e x p e r i m e n t w i t h l ambs and p r o v e d t h a t l a c k o f e x e r c i s e and s u n l i g h t would n o t p r od uc e s t i f f l ambs as was s u s p e c t e d two 10 4 y e a r s b e f o r e . M l l m e n e t a l (1931) confirmed the e a r l i e r work i n p r o d u c i n g t h e d i s e a s e e x p e r i m e n t a l l y by f e e d i n g p r e g n a n t ewes h i g h p r o t e i n g r a i n m i x t u r e s t o g e t h e r w i t h a l f a l f a o r c l o v e r hay c o mb i n e d w i t h a l a c k of e x e r c i s e . t h e seme r e p o r t , In the a u t h o r s mentioned t h a t t h i s d i s e a s e had been r e p o r t e d from P e n n s y l v a n i a , M a r y l a n d , Ohi o, Mi c h i g a n , W i s c o n s i n , Mont ana , Oregon, and Nevada. SO Marsh , i n 1932, m e n t i o n e d t h a t t h e w r i t e a p p e a r a n c e o f muscl e f i b e r s i n " s t i f f l a mb s " d i s e a s e was due t o a d e p o s i t o f t r i c a l c i u m p h o s p h a t e and c l a i m e d t h a t t h e r e was a d i s t u r ­ bance o f n o r m a l c a l c i u m and p h o s p h o r u s b a l a n c e i n t h e a f f e c t e d l ambs. In 1934, 93 S l a g s v o l d and L u n d - L a r s e n ^ d e s c r i b e d a p e c u l i a r -1.0d i s e a s e o f young lambs and c a l v e s i n Norway. The c h i e f l e s i o n s c o n s i s t e d of m u s c u l a r d e g e n e r a t i v e c h a n g e s , h a v i n g some s i m i l a r i t y t o h y a l i n e d e g e n e r a t i o n b u t d i f f e r i n g from it, by a more p r o n o u n c e d t e n d e n c y t o d e p o s i t i o n o f c a l c i u m . No s p e c i f i c o r g a n i s m or c o n d i t i o n was d e m o n s t r a t e d a s t h e cause. Adequat e r a t i o n s o f m i n e r a l s and v i t a m i n s g i v e n t o p r e g n a n t ewes was c o n s i d e r e d a s an e f f e c t i v e p r e v e n t i v e measure. A p p a r e n t l y , t h e a u t h o r s wer e d e a l i n g w i t h w h i t e mus cl e d i s e a s e . In t h e same y e a r ( 1 9 3 4 ) , wi l i man e t a l 105 published the r e s u l t s of f o u r y e a r s ' work and gave a r a t h e r e x t e n s i v e a c c o u n t of t h e c a u s e and h i s t o p a t h o l c g y of " s t i f f - l s m b " disease. They were a b l e t o p r o d uc e t h i s c o n d i t i o n by f e e d ­ i n g t h e p r e g n a n t ewes a r a t i o n ( t h e " s t i f f - l a m b '1 r a t i o n ) c o n s i s t i n g o f s e c o n d - c u t t i n g a l f a l f a hay and a m i x t u r e of 3 p a r t s of o a t s , 3 p a r t s of b a r l e y , and 4 p a r t s o f c u l l b e a n s , and p r o v e d t h a t n e i t h e r e x e r c i s e f o r t h e ewes d u r i n g t h e w i n t e r n o r heavy f e e d i n g o f c o n c e n t r a t e s or c r e e p - f e e d i n g of t he l ambs was t h e c h i e f c a u s a l f a c t o r . They a g r e e d w i t h 84 Met zger and H a g a n ' s work i n most r e s p e c t s but c l a i m e d t h a t cl umps of mo n o n u c l e a r p h a g o c y t e s and n e u t r o p h i l s wer e found in the l e s i o n s . The n e x t y e a r ( 1 9 3 5 ) , Lee and S c r i v n e r 1' c a s e s of " s t i f f - l a m b s " i n Wyoming. made a. s t u d y of They f o u n d t h a t t h e g r o s s l e s i o n s were somewhat v a r i a b l e and c o n s i s t e d o f a r t h r i t i s , w h i t e s k e l e t a l muscl e l e s i o n s , g r a y i s h w h i t e a r e a s and s t r e a k s i n t h e h e a r t and i n t h e k i d n e y s . M i c r o s c o p i c exa mi n a ­ t i o n of t h e w h i t e s k e l e t a l mus cl e l e s i o n s showed d e g e n e r a t i o n , -17c e l l u l a r and c a l c i u m s a l t i n f i l t r a t i o n s . The h e a r t and k i d n e y l e s i o n s we r e f o u n d t o be a r e a s o f c o a g u l a t i o n n e c r o s i s and p u r u l e n t f o c i . Ch e mi c a l e x a m i n a t i o n showed an i n c r e a s e i n c a l c i u m and p h o s p h o r u s . Besides, the authors wer e a b l e t o i s o l a t e t h r e e d i f f e r e n t k i n d s o f b a c t e r i a f rom h e a r t b l o o d , n a m e l y , b i - p o l a r r o d s , non-spore-forming rods, cocci, and and t y p i c a l l e s i o n s wer e r e p r o d u c e d e x p e r i m e n t a l l y i n l ambs a n d r a ' b b i t s by means o f i n o c u l a t i o n with these b a c t e r i a . A p p a r e n t l y , Lee and S c r i v n e r wer e d e a l i n g w i t h c a s e s of w h i t e - mu s c l e d i s e a s e c o m p l i c a t e d by bacterial infection. Wi l l man e t a l (193-5) 10 6 sought to determine i f the d i s e a s e was c a u s e d by a l a c k of v i t a m i n C ( a s c o r b i c a c i d ) . They c o u l d n o t p r e v e n t t h e d i s e a s e by t h e a d d i t i o n o f a s c o r b i c a c i d to the new-born lambs. These l a m b s were f r o m ewes f e d w i t h " s t i f f l a mb " r a t i o n a s l o n g a s f i v e weeks a f t e r b i r t h . The r e s u l t s i n d i c a t e d t h a t t h e d i s e a s e was n o t due t o a vitamin C d eficien cy . I n 1936, Wi l l ma n e t a l 107 was t h e c a u s e o f t h e t r o u b l e . t r i e d t o t e s t w h e t h e r t h e hay The s o - c a l l e d "stiff-lam b r a t i o n " was f e d t o t h e ewes c u t mi xed c l o v e r and t i m o t h y hay was u s e d i n p l a c e of a l f a l f a h e y . t h i s l o t became s t i f f , m i x t u r e and n o t Ten o f t h e 19 l a m b s i n which i n d i c a t e d t h a t t h e c o n c e n t r a t e t he hay was t h e p r i m a r y c a u s e o f t h e d i s e a s e . I n 1937 , t h r e e a r t i c l e s d e a l i n g w i t h v a r i o u s p h a s e s o f white-muscle d isea se appeared. that Anderson's article stated "t he c a l c i u m of t h e s erum o f l a m e s a f f e c t e d w i t h s t i f f - i a m o -18d i s e a s e was l o w e r and t he p h o s p h o r u s h i g h e r t h a n t h a t of n o r ma l l a mb s . Many of t h e d i s e a s e d l a mb s showed h i g h e r g l u c o s e and. n o n - p r o t e i n n i t r o g e n v a l u e s , and l o w e r c h l o r i d e va lu e s than normal lambs." The s e c o n d a r t i c l e was from t h e 70 Montana V e t e r i n a r y R e s e a r c h L a b o r a t o r y whi ch summar i zed t h e e x t e n t of t h e d i s e a s e as f o ll o w s : "On some f a r m s t h e l o s s e s due t o w h i t e - m u s l c e d i s e a s e r e a c h e d 30- 40$ and on others, 5$ o r l e s s . A t h i r d of them e v e n t u a l l y r e c o v e r e d . " The t h i r d a r t i c l e on " s t i f f - l a m b s " was p u b l i s h e d by t h e 114 Wyoming De p a r t me n t of V e t e r i n a r y S c i e n c e and a p a r a g r a p h of i t r e a d a s f o l l o w s : "A f ar m f l o c k o f about 400 ewes p r o d u c e d a b o ut 1 0 p e r c e n t s t i f f l a mbs one y e a r w i t h o u t n a v e l i n f e c t i o n when f e d on r a t h e r p o o r w i n t e r r o u g h a g e s u p p l e m e n t e d by n a t i v e hay d u r i n g s t o r my w e a t h e r . For two y e a r s f o l l o w i n g , when t h e r a t i o n i n c l u d e d a l f a l f a n a y , and a m i x t u r e o f m i n e r a l s , grain, only 1 p er ce n t of lambs developed symptoms of . . . st i f f ness-! !. . - ■JEhe-s.e. - r e s u l t s ' seemed t o - be- - qui t e—■ c o n t r a d i c t o r y t o t h e r e s u l t s o b t a i n e d by Wi l l man a n d h i s associates. nriggs et al ( 1 9 3 8 ) 9 made an a t t e m p t t o s t u d y t h e c a u s e and c u r e of " s t i f f j o i n t s " . They b o u g h t 12 ewes t h a t had. typical s tif f and t h e s e a n i m a l s wer e t h e n l ambs a t s i d e , p l a c e d on s m a l l wheat p a s t u r e s . in ad d itio n to mixture. The m o t h e r s were f e d n o t h i n g t h e a b u n d a n t wheat p a s t u r e but a s i m p l e m i n e r a l A h e a v y mi lk f l o w r e s u l t e d from t h i s f e e d . The a f f e c t e d l ambs n u r s e d w e l l and made n o t i c e a b l e r e c o v e r i e s . In t he same y e a r (1938), S ch ofield 86 made a. s t u d y of t h e -19 h i s t o - p a t h o l o g y o f " s t i f f l amb" d i s e a s e . He f o u n d d e g e n e r a ­ t i o n and f r a c t u r e of t h e m u s c l e f i b e r s w i t h c a l c a r e o u s i n f i l t r a t i o n of the fragm ents. C e l l u l a r i n f i l t r a t i o n was n o t e x t e n s i v e b u t both p o l y m o r p h o n u c l e a r and. r o u n d c e l l s were p r e s e n t . I n t h e f i n a l s t a g e s t h e r e was c e l l u l a r i t y of t h e a f f e c t e d m u s c u l a r t i s s u e s due t o p r o l i f e r a t i o n o f f i b r o b l a s t s and m u l t i p l i c a t i o n of t h e n u c l e i of t h e There was m o d e r a t e c e l l u l a r s ar col emma. i n f i l t r a t i o n and n u me r ou s p o r t i o n s of damaged mu s c l e r e m a i n e d i n t h e c e l l u l a r mass. Besides, t h e l i v e r was f o u n d t o h a v e s m a l l c l u s t e r s o f 1 0 - 2 0 poly­ m o r p h o n u c l e a r c e l l s and a d e f i n i t e h y p e r p l a s i a o f t h e s e c r e t o r y e p i t h e l i u m was o b s e r v e d i n t h e e n l a r g e d t h y r o i d . fl i l i man e t a l 108 , i n 1938 , u n d e r t o o k e x p e r i m e n t s t o d e t e c t t he e f f e c t o f f e e d i n g d a l l y d o s e s of cod l i v e r o i l t o t h e l a c t a t i n g ewes and by s u p p l e m e n t i n g t h e r a t i o n w i t h d i - b a s i c sodium p h o s p h a t e . n o t c o m p l e t e d , no d e f i n i t e In 1939, "stiff-lamb" S i n ce t h i s work was c o n c l u s i o n was drawn. S c h o f i e l d and Bai n 87 reported that " s t i f f lamb" d i s e a s e was an. a p h o s p h o r o s i s b e c a u s e t h e y f o u nd t h a t a. s m a l l g r o u p o f a f f e c t e d lambs r e c o v e r e d a f t e r d i l u t e phosphoric acid in m ilk. Snoll r e c e i v i n g : d o s e s of i n t h e seme y e a r r e p o r t e d t h e o c c u r r e n c e of s t i f f - l a m e d i s e a s e i n Mi chi gan where l o s s e s f r o m t h e a f f e c t i o n were v e r y heavy (30fc l o s s on some f a r m s ) . Bl o o d c h e m i s t r y d e t e r m i n a t i o n s were made, and low c r e a t i n i n e and h i g h n o n - p r o t e i n n i t r o g e n were f o un d. 100 Vawt er and R e c o r d s (1939) o b s e r v e d " whi t e m u s c l e " d i s e a s e o f lambs from ewes r e c e i v i n g a l f a l f a hay a l o n e b u t n o t i n -2 0 ewe b r e c e i v i n g a l f a l f a p l u s r o l l e d o a t s . The a u t h o r s had t h e f e e l i n g t h a t t h e d i s e a s e mi ght be due t o a p h o s p h o r u s d e f i c i e n c y , b e c a u s e t h e a l f a l f a hay i n Reno, N e v a d a , was somewhat low i n p h o s p h o r u s w h e r e a s r o l l e d o a t s was a good s o u r c e of p h o s p h o r u s . B e sid e s, they f e l t t h a t the term " s t i f f lambs" was c o n f u s i n g and s h o u l d be s e p a r a t e d from t h e t e r m " whi t e muscl e " d i s e a s e . , \109 H i l l m a n e t a l (1939) c o n t i n u e d t h e work w i t h t he " s t i f f lamb" r a t i o n s u p p l e m e n t e d w i t h p h o s p h o r u s , b u t no si pni f i c a n t r e s u l t s wer e f o u n d a f t e r usi np' t h i s el a m e n t • - vj o In 1940, H i l l m a n e t a l t h r e e p r e v i o u s y e a r s wor k. 110 s ummar i zed t h e r e s u l t s of t h e The d i s e a s e was of n u t r i t i o n a l o r i g i n ana was n o t p r e s e n t a t b i r t h . silage, * ■ The f e e d i n g o f maize Done meal or sodium p h o s p h a t e t o t h e ewes f a i l e d t o p r e v e n t t he c o n d i t i o n , as d i d d r e n c h i n g t h e young l ambs w i t h t he e q u i v a l e n t o f 60 - 13 0 mgm. a s c o r b i c a c i d p e r week. The i n c i d e n c e - o f - t h e - d i s e a s e a p p e a r e d t o ' be m a r k e d l y ' "reduced i n a c o n t r o l l e d e x p e r i m e n t i n whi c h u n e x t r a c t e d w h e a t germ meal was added t o t h e b a s a l m a t e r n a l d i e t o f o a t s , barley, c u l l beans and l u c e r n e h a y . In t h e same y e a r ( 1 9 4 0 ) , M i l l s 67 c o n s id e re d t h a t the t e r m " s t i f f l ambs" r e f e r r e d mer el y t o a s i n g l e symptom and not t o any s p e c i a l e n t i t y a n d he f e l t t h a t i t was a d v i s a b l e t o d i s c u s s t h e c o n d i t i o n s u n d e r a h e a d i n g whi ch r e l a t e d t o e t i o l o g y r a t h e r t h a n t o symptoms. He r e c o g n i z e d f o u r c a u s e s of l a me n e s s i n l ambs, t o wh i c h t h e t e r m " s t i f f l a m b s " was commonly a p p l i e d , and t h e y we r e : (l) Erythropelothrix rhusiopathiae infection, o l d l ambs, and (4) ( 2) tetanus, (3) "feed a l l e r g y " in " f e e d a l l e r g y " i n unweaned l a m b s . The al l er gev; c s u b s t a n c e a l s o a p p e a r e d t o be p r e s e n t i n t h e e w e ' s milk. Apparently, M i l l s c o n s i d e r e d " w h i t e mu s c l e " di sea. se a s a symptom o f " f e e d a l l e r g y " a l t h o u g h he d i d n o t m e n t i o n i t . Ill Willraan e t a l i n 1941 c o n t i n u e d e x p e r i m e n t s on t h e " s t i f f lamb" r a t i o n w i t h and w i t h o u t e x t r a c t e d wheat-germ meal. l amb" r a t i o n , the a d d i t i o n of un­ Wi t h t h e ewes f e d t h e "stiff e l e v e n of t w e n t y - s e v e n l ambs became s t i f f . No s t i f f l ambs d e v e l o p e d i n t h e w h e a t - g e r m s u p p l e me n t e d , l o t , I n t h e same y e a r (1941) t h e Oregon S t a t i o n 79 r e p o r t e d the o c c u r r e n c e of " s t i f f l ambs" and s t a t e d t h a t no o r g a n i s m was f ound in. c o n n e c t i o n w i t h t h e d i s e a s e . 62 In 1942, Me l a s s c a r r i e d out f u r t h e r i n v e s t i g a t i o n on t h e ca us e o f s t i f f lamb d i s e a s e and m e n t i o n e d t h a t s e v e r a l p o s s i b l e f a c t o r s were r e s p o n s i b l e f o r t h e c o n d i t i o n . Of t h e s e f a c t o r s , _ h i g h prot ei n. . ^cont ent - o f t n e . . r a t i o n !, , J c y s t i n e . deficiency), p r e s e n c e of t o x i c s u b s t a n c e i n t h e r a t i o n , and t h e q u e s t i o n o f m i n e r a l i n b a l a n c e wer e a l l p o s s i b l e b u t needed f u r t h e r study. . 35 S a l y i ( 1 9 42 ) d e s c r i b e d a d i s e a s e i n young l a mb s which showed c a r d i a c and s k e l e t a l mu s c l e d y s t r o p h y . t i o n of t h e d i s e a s e was g e n e r a l l y f a t a l ; arthritic, death. The t e r m i n a ­ o r o n c h o p n e u mo n i c , and e n t e r i c c o m p l i c a t i o n s o f t e n s u p e r v e n e d b e f o r e The g r o s s l e s i o n s wer e t y p i c a l g r e y o r g r e y i s h - y e l l o w a r e a s i n t h e h e a r t and s k e l e t a l m u s c u l a t u r e . investigations proved n e g a tiv e , Bacteriological and n u t r i t i o n a l d e f i c i e n c i e s I P r o b a b l y S a l y i was d e a l i n g w i t h t y p i c a l wer e s u s p e c t e d . c a s e s o f w h i t e muscl e d i s e a s e c o m p l i c a t e d by some o t h e r infections. Willrnan e t a l (1944) 11? c o n d u c t e d an e x p e r i m e n t wi t h t h r e e l o t s e a c h o f ?4 ewes and t h e i r l ambs t o d e t e r m i n e w h e t h e r or n o t " s t i f f lamb" d i s e a s e c o u l d be p r e v e n t e d by f e e d i n g s u p p l e m e n t s of v i t a m i n E t o a r a t i o n ( c u l l beans and a l f a l f a h a y ) t h a t p r o d u c e d t h e d i s e a s e . As a r e s u l t , 36 o f 38 l ambs became s t i f f when r a i s e d by ewes f e d t h i s vi i. o .j.i w iig « u u n V' n o *■ ts.a. O n H two d o s e s weekl y of 9 c c . r> w a. "♦*Vi V> 'w»- o ^ in r> O *->y o r*. r>l A -r\ »-» -l o v-*- 4. .t i .J 4- ■ ? — u u u i v. ) a p e r ewe o f an 8 . P 5 p e r c e n t s o l u t i o n of mixed t o c o p h e r o l s i n c o t t o n s e e d o i l t w e n t y - f o u r days b e f o r e l a m b i n g or by t r e a t i n g t h e l ambs w i t h S c c . o f an o l i v e o i l s o l u t i o n of 140 mgm. o f a l p h a - t o c o p h e r o l a c e t a t e . Tr e a t me n t of t h e a f f e c t e d l ambs w i t h 100 mgm. of w a t e r s o l u b l e d i s o d i u m s a l t o f d. 1 - a l p h a t o c o p h e r o l p h o s p h o r i c “ : . a e i d -ester- was ■f r i e d 1'"and: p r o v e d q u l t e - ' e f l e c t l v e ^ l n "un- "■ complicated cases. B e s i d e s t h o s e s p e c i a l wor ks j u s t c i t e d , w h i t e muscl e d i s e a s e was a l s o 59 0 0 b r i e f l y m e n t i o n e d by Ma r s h 1/ * Howart h (Q Montana V e t e r i n a r y R e s e a r c h L a b o r a t o r y n <^1? , q , Oregon S t a t i o n rv ■ 23 Qft ' 17 Dykstra e t a l , Thorp" , a n d Care under the headin g " d i s e a s e s o f n e w- b o r n l ambs i n g e n e r a l " . 7. Miscellaneous Diseases Bacterium c o l i i n f e c t i o n . was r e p o r t e d by Volkova i n 1933. T h i s d i s e a s e d c o n d i t i on E i g h t e e n n e w - b o r n lambs -PSd i e d f o l l o w i n g am i l l n e s s l a s t i n g f r om ?>0 m i n u t e s t o 30 h o u r s a f t e r t h e a p p e a r a n c e of i n i t i a l symptoms o f t r e m b l i n g , stumbling, and h i g h t e m p e r a t u r e s b u t no d i a r r h e a . I n each c a s e , t h e b a c t e r i o l o g i c a l e x a m i n a t i o n showed c u l t u r e s o f B a c t e r i u m c o l i v i r u l e n t b o t h f o r l a b o r a t o r y a n i m a l s and f o r a lamb when g i v e n i n t r a v e n o u s l y . (p) Dyse n t e r y . from Montana 10 3 Lamb d y s e n t e r y was r e p o r t e d by Welch e t a l , 19P9. I t was s t a t e d t h a t d y s e n t e r y o c c u r r i n g i n Montana d i f f e r e d i n so many r e s p e c t s from t h e E n g l i s h Inmb dyRppt er y t h a t t h e r e s u l t s o b t a i n e d i n ( t r e a t B r i t a i n were of l i t t l e Montana. o r no v a l u e i n c o n t r o l l i n g t he d i s e a s e i n The a u t h o r s c l a i m e d t h a t a c o m b i n a t i o n o f c o l d , wet we a t h e r and t h e p r e s e n c e o f s t r a i n s of i n t e s t i n a l b a c t e r i a was r e s p o n s i b l e f o r s uch d i s e a s e d c o n d i t i o n r a t h e r t h a n a s p e c if ic pathogenic micro-organism. / V (3 ) Navel i n f e c t i o n . I n 1934, B u l l a r d 16 published a -o-as-e-neport^on-nav-el" i n f e e l l o n ' of - a. ■■■■lamb'--. " -*P u x making a t o t a l of 71. i«3t r o o u ix y • A• Met hods f o r s t u d y i n g b l o o d and b l o o d c h e m i s t r y . (a) Blood s t u d i e s o n n o r m a l a n i m a l s . S i n c e a s t u d y of t h i s k i n d i s r a t h e r new and d a t a from o t h e r w o r k e r s meager , i t was n e c e s s a r y t o d e t e r m i n e t h e b l o o d p i c t u r e end b l o o d c h e m i s t r y o f n o r m a l l ambs f o r c o n t r o l p u r p o s e s and normal ewes as a c h e c k - g r o u p b e f o r e a t t e m p t i n g t o s t u d y p a t h o - ‘lo glc a l 'cases r : ■' ' .... .. ''- ' A P - i n c h 1 6 - g a u g e n e e d l e or 3 - i n c h 15-ga.uge n e e d l e (the s o -called draw 1.5 c c . 8 " C a l i f o r n i a b l e e d i n g n e e d l e " ) was u s e d t o o f b l o o d from t h e j u g u l a r v e i n ( f r om e a c h of n o r ma l l ambs and 8 n o r m a l ewes) i n t o a t e s t - t u b e c o n t a i n ­ i n g dry p o t a s s i u m o x a l a t e ( s e v e n d r o p s o f a 33 p e r c e n t s o l u t i o n d e l i v e r e d from a 1 c c . p i p e t t e a f t e r h a v i n g been evaporated to dryness in a hot oven). As soon as enough b l o o d was o b t a i n e d and t h e n e e d l e was l o o s e n e d from t h e v e i n , a t l e a s t t h r e e b l o o d s me a r s were i m m e d i a t e l y made by t i p p i n g t n e n e e d l e and a l l o w i n g a s m a l l d r o p o f bl ood t o c o l l e c t on -26t h e end o f t h e c l e a n s l i d e s a f t e r wh i c h e ach d r o p was s mo o t h l y pushed f o r w a r d by t h e end of a n o t h e r c l e a n s l i d e so as t o g e t a u n i f o r m s m e a r . The s m e a r s were i n s t a n t l y d r i e d by wa v i n g them i n t h e a i r and t h e y wer e t h e n s a v e d f o r d iff e r e n tia l counts. At t h e same t i m e , t h e b l o o d - s a m p l e i n t h e t e s t - t u b e was c o n s t a n t l y b u t g e n t l y r o t a t e d p r e v e n t t h e b l o o d from c l o t t i n g . Each in order to of theseblood s a m p l e s was t o be u s e d f o r t h e c e l l u l a r c o u n t , h e m o g l o b i n determination, and c h e m i c a l a n a l y s i s . irio; such normal The t i m e f o r b l e e d - s h e e p was p u r p o s e l y a r r a n g e d t o c o v e r a c o n s i d e r a b l e l e n g t h of t i m e . t w i c e , once on May 4, 19 4 4 , The n o r m a l l ames we r e b l e d and. a g a i n on June 1, 1 9 4 4 , e ach b l e e d i n g b e i n g c a r r i e d o u t on f o u r a n i m a l s . bled at five d i f f e r e n t times, one e a c h A p r i l 7, A p r i l 2 0 , and f o u r on June 1 , The c o u n t i n g of b l o o d was made a s The ewes were on A p r i l 4, A p r i l 6 , 1944, s oon as t h e b l o o d -"'-""-Sample'S"' re-ach-e-d ■•4he-~l-abora*t0-ry-v- "The' ’©rdi-nary^me^hO'Clr. of--'" b l o o d c o u n t i n g was empl oyed so t h a t t h e d e t a i l e d p r o c e d u r e w i l l n o t be m e n t i o n e d h e r e . Leake and Gu y ' s p l a t e l e t d i l u ­ t i o n f l u i d was u s e d f o r r e d b l o o d c e l l c o u n t s . The d i l u t i n g f l u i d f o r w h i t e b l o o d c e l l c o u n t s c o n s i s t e d of 8 cc . d i s t i l l e d w a t e r i n a s m a l l v i a l t o wh i c h was ad d e d 4 dr ops of Gram' s c r y s t a l v i o l e t . Bo t h d i l u t i n g f l u i d s we r e f o u n d t o be q u i t e s a t i s f a c t o r y . For m i x i n g b l o o d c e l l s , blood p ip e tte r o t o r (Bryan-Gerry) ue v e r y w e l l a d a p t e d t o t h e wor k. diluting pipettes, was u s e d and i t the seemed t o In o r d e r to c l e a n s e the a s e t o f home-made s u c t i o n b o t t l e s with, t h e * S o l d oy A. 3. Aloe Co . , St. Louis, M issouri. -•-. a i d of a r u b b e r p i p e t t e a d a p t o r was f o u n d t o be Q u i t e e f f i c i e n t . For h e m o g l o b i n d e t e r m i n a t i o n , was s t r i c t l y f o l l o w e d ingly prepared, 40 . S h e a r d - S a n f o r d 1 s method The n e c e s s a r y s o l u t i o n s wer e a c c o r d ­ ana t h e r e a d i n g was made by means o f a Cenco-Sneard-Sanford p hotolom eter. i n t e r m s of gram per 1 0 0 c c . The v a l u e o f h e mo g l o b i n o f b l o o d was d e t e r m i n e d a c c o r d ­ i n g t o t he c a l i b r a t i o n c h a r t p r o v i d e d by t h e C e n t r a l S c i e n t i f i c C o., C hicago, 1 1 1 . For c h e m i c a l a n a l y s i s o f t h e b l o o d , t h e me t h od s of 40 /< . S. Hoffman were f o l l o w e d w i t h t he e x c e p t i o n of b l o o d chloride determination. Five d i f f e r e n t ol ood c omp on e n t s wer e d e t e r m i n e d by t h e s e m e t h o d s , n a me l y , g l u c o s e , u r i c a c i d , c r e a t i n i n e , n o n - p r o t e i n n i t r o g e n ( N. P . M. ) , and u r e a - n i t r o g e n . 36 i V h i t e h o r n 1 s met hod was u s e d f o r t h e d e t e r m i n a t i o n o f b l o o d chloride. The bl ood s me a r s were s t a i n e d w i t h W r i g h t ' s s t a i n , etrieb"," ""and' Gou nt ed- u n der " t he - ' - mnc r n s o op e - l y- l i h e - no - e a l l e hh - " " ' ■ 52 " b a t t l e m e n t " o r " p a l i s a d e 11 me t hod. The r e s u l t s o f t h e p r e l i m i n a r y s t u d y of b l o o d a r e summarized, and a r r a n g e d i n T a b l e s ( l ) and ( 2 ). :. Table ( l ) at i ’i e s j No. | 4 i L | (J : Ti e b l o o d p i c t u r e o f n o r m a l Iambs e n d ewes Io e n tif ie at i o n No. ii I * i 14a-??3 ? ? - l 79 ? 7-469 3 0 - 9 79 9 43 i | Surooshire | 1 H | Oxford | B l a c k Tpp I Delaine n 9 AA ! 1 n 945 1 i 9 50 jR a m o o u i l l e t |i ----------- ------ ---------- h 'tr r, ° 5 i 3 Do t e Bled Age ( D g y s) Br e ed | ! Ii A*£ p e r c.m.m. 19J f is g AH - oo ■ ' i■|.i.’ . r'j 1 1 . 9 50 , 0 ' ); 19 .9 80/= / I 9,0 70,0001 O b 1 0 , 3 7 0 ,0 0 0 ' I* . 1 5/4/44 53 73 i D 71/44 » " 59 64 7? ! 1 0 „670 . 0 PO Lr- . r !1 0 730 l o o o 1 1 . 8 i 1 0 , 550 , 0 0 0 11.1 i P' or 7 1.arnbs Av e r a g e , 444 P 3 6 1 I | 1 0 , 457 , 800 ___ 10 . 9 ? 1 10 of normal s t a n d a r d For 8 l a mb s "L P 3 4 5 C 7 i 8 7 356E 7358E 7360E 7 39 3 E 1? 13 19 P. 5 |b h i t e - f a c e Grade (Hampshire (Shropshire n ii ii ii RemDouillet Aver sere o r n o r m a l s t a n d a r d 4 yr. 5 yr. 4 yr. ?, y r . b yr. 5 yr. 9 yr . 4 yr. i ! ! 1 1! --------------------------_________________ _| ---------------- ---- 4/8/44 J4/7/44 14/? 0 / 44 ( 3 / 1 / 44 1 ! ! Hb. Gm. $ ' ft i L n ! .10 830 , 0 0 0 6 , 590 , 0 0 0 9 _. 0 0 3, 380 , 0 0 0 'l ?! , 70 1 0 , 900 , o o q 10 4*3 O >> ? 380 t onH - ■ •' 11 /JO 490 1 n' . o■ o , 45 7 390 . 0 0 0 >5 7 1 0 , 900 , 0 0 0 3, 60? Note: ft. B. C.......................... Red b l o o d c e l l c o u n t K b ......................................H e m o g l o b i n v a l u e 1J. B. C ......................... W h i t e o l o o d c e l l c o u n t 0 ........................................ K e u t r o p n i I s L ........................................ Lymph ocy t e M........................................ Monocy t e ** Lamb 950 p r o b a b l y h a d some i n f e c t i i n , a n d i t m g h t be oim t t e d , a l t h o u g h t h e a v e r a g e d v a l u e s o f 3 a n i me I s we c a lc u la te d in the t e b l e fo r r e f e r e n c e . rt r 'p 9 J J H id. e w e s . Hb . Gm. *jo W. B. C. u e r c. mm 10.340.000 11,9 50,000 10.980.000 9.070.000 10.370.000 11 .0 8.5 19.5 7.8 19.1 10.670.000 9.730.000 10.550.000 19.5 11. 8 TT7~BT“ CT per c.mm, D ifferen ti al leucocyte N L 10 , 6 50 7 , 0 50 5 , 400 5 , 400 9,250 19 34 } 80 20 | 77 | 58 | 60 22 21 11.1 8,950 9 , 150 19,000 10,444,2 86 10.90 7,979 88 70 0 !I 1x 0j ,. ^.5o7r f 800 ajj l0>gp 9,356 31 66 0 . 5-1 10 .10 5 , 850 80 76 39 39 58* * count, E B 1 1 66 1 1 r< 2 1 | 77 I 75 | 35 1 1 3 7 .57-1 1 . 3=1 2 "I 6.830.000 6 , 590. , 00 0 3, 8 8 0 , 0 0 0 10.900.000 9.330.000 7, 49 0,000' 7 , 3 9 0 , 0 00 10.900.000 8,60 7,000 9 18.7; 10.4; 11.40 8 . 45 9 .90 9.80 10 .08 -.10,.45Q,. 5 , 7 00 15,400 5 , 300 7,150 6 , 450 9 , 800 8,863 13 4:0 38 38 93 88 30 Eosinophils Basophils t m i g h t be an im als were 2 -63 79 56 56 2 •*1- 8 4 6 62 65 55.25 1 0.37-1' 6 7 0 T able “ Se­ ries No. (2). Chemi c a l 5 / b l o o d o f n o r m a l l a m b s and, ewe s . Uric Ac i d Mgm . 'jo Glucose Mgm. Jo Date Bled Identificat i o n No. Lamb | 1 i 1 4a. - 9 93 2 ! 22-179 3 i 2 7 —469 ! 4 32-979 9 4-3 l 5 9 44 ! 6 l 7 9 45 9 50* ! s a n a ly s is of 4 / 44 1.55 1.55 1 . 50 1 . 55 1.90 2. 35 61.00 71.11 65.00 80 . 0 0 5 7 . 50 67.00 62.00 5 5 . 50 ' ii It " 6/1/44 ii " ti Cre­ atinine Mgm. jo 0.80 j 0 .78 0 .80 1 . 40 1 . 20 C hlo- | N. P .N r i de Mgm .jo Mgm. jo | 1 . 30 1.10 1.20 1.00 3 90 46 0 ! 410 440 460 47 0 47 0 420 1.71 1.04 440 0.40 0.60 0 . 40 0.80 350 420 365 | 4-60 380 440 450 4 fin 2.00 1 Ewe I 1 ! 2 3 4 5 r* o 7 8 12 . ..... 64.89 r 7356(E) 7358(E) 7362(E) 7393(E) 13 19 25 4/4/44 i ! ! 4/6/44 | 4/7/44 j 4/20/44 S 6/1/44 1 | i " ! ! » j Averaged v a lu e or Normal S t a n d a r d t l 17.8 j 38.00 j 27.6 1 2 .2 32.8 j 1 2 .2 35.6 j 13.0 27.0 I 15.8 | 36.0 13.5 ! 36.0 14.9 26.0 13.0 . Averneed value or Normal S t a n d a r d ! 1 i UreaN Mgrn .jo 38.00 85.00 30 . 71 51.82 43.30 37.00 50.00 52.00 4 8 . 48 32.37 14.17 30.0 30 . 0 16.8 7.5 14.9 ■ 0 .22 1.10 ! 2.22 1.65 2 .10 1.90 1 . 48 1.9 5 1.20 1.10 1.00 ! . 20 1 . 58 0.84 20.0 I i 415. Or 24. 5 41.0 41.0 36.0 dfi.O 31.31 11.2 ; 18.2 21.8 14.9 .1.5.,8 . 15.14 Not e : * The c h e m i c a l a n a l y s i s o f b l o o d o f l a m b No. 9 5 0 d i d n o t show a n y m a r k e d d i f f e r e n c e fro m t h e o t h e r n o r m a l a n i m a l s s o t h a t i t was in c lu d e d in th e c a l c u l a t i o n of av erag ed value fo r the normal standard. P r o b a b l y , t h i s may b e o n e r e a s o n t o e x p l a i n why t h i s lamb a p p e a re d normal a t th e time o f b l e e d in g a lth o u g h i t s b lo o d p i c t u r e s h o w e d some k i n d o f i n f e c t i o n a s m e n t i o n e d a b o v e ( T a b l e l ) . ' -30Table lam bs. (l) Th e c.mm ., count of per count 100 decidely low er From T a b l e is lam bs i s 100 blood in im ate each (2) ewes), study standard of the the and fact available summarized that in those w hile per the c.mm.) were n e a r l y average normal elem ents in the in ewes per the (4$) sarnie. values, glucose 4 8 . 4 8 mg. as to use a control the last cases yean, a to tal blood study. in Table (3). presented the on in in oi normal (64.89 100 mg. cc. blood values approx­ as by u s i n g For the The d e t a i l e d connection cases. the The same each blood methods lam bing c a s e s was herew ith account w ith cases. entire are respect, a normal pathological The r e s u l t s prelim inary every pathological studied of 12 this s.lmost pa t h o lo g i c a l anim als. for be these for was normal the r e s u l t s constant B lood s tu d ie s em ployed f o r of that olood found other lfo m o n o c y t e , s ame a n i m a l s the the against were r a t h e r p ath o lo g 'ical w ill lam bs justifiab le (b) season in that tne figures drawn, than d ifferential (8,607,000 to per com pated w ith note of and r e f e r r i n g be average are to normal 8 and h e m o g l o b i n 7 0 L]o l y m p h o c y t e s , rem aining w hile on b l o o d seemed The values of was 1 0 ,4 4 4 ,2 8 6 c.mm ., blood. these can c e l l value other. In view ings per of n o r m a l ewes the blood count in teresting much h i g h e r cc. blood and e o s i n o p h i l s generalization from of If count decidedly h ig h er, it cc. it blood c e l l per 7,979 showed 2 8 n e u t r o p h i l s , normal ewes, one average erythrocyte vjo e o s i n o p h i l . red is average leukocyte 1 0 . S grams and shows t h e of the briefly find­ individual case. -31- Taole Case lTo. (3) . A s u m m a r y o f p i o o d s t u d i e s on p a t h m ^ i n Bi Xarab_ R . 5 . C. * p e r c.mm. Hb. cm . 'jo i gill W. b . C . p e i c . mm. 7338 10, 400,000 11.4 12,150 Di. f f e r e n t i a l l e u c n r v + P count tie? u t r o] o h i l s s i L P il. b IP Fi L «-> 12 c 79 3 7343 5,310,000 6.3 1 4 , 900 14 3 46 7 ,9 7344 8,990,000 11.4 800 74 8 8 4 6 7393 , 740 , 0 0 8,710,000 ! I P . 26'~' 6.8 12.0 23,900 1 4 , 600 18 73 7 2 7 5 . 55 74.44 9.8 1 1 , 600 7 88 4 I 196.00 6.3 1 3 , 2 50 2 35 47 9 35 6 3 4 29 3 77.77 43 24 22 2 0 0 .0 0 I------------- 7394 ? 3dg 6 7358 9,370,000 7362 7400 8,670,000 10,0 70,000 9.8 10.3 9 , 9 50 6,150 18 56 4-6 7406 10,390,000 10.3 1,700 6 5 7415 8,970,000 7.8 14,150 2 78 7 47 4 a. 9 , 0 70 , 0 0 0 10.8 2, 200 37 40 1 18 l Chernies 15.00 H I ! 41.66 28.00 115.00 7 97.50 170.00 2 i l 88.75 *E x p l a n a t i o n o f t h e a b b r e v l a t i ons : 9^ ..................... Keci Dl o od c e l l c o u n t H b ................................. Hem o g l o b i n * V/. C .................... W h i t e b l o o d c e l l c o u n t L ....................................L y m p h o c y t e s M....................................M o n o c y t e s E.................... EosinoiJhils H....................................B s s o p h i I s s .............s egment e ng b .............b a n d s . 1 .............j u v e n i l e s my e l o c y t e s G U C c N U C h e m i c a l a n a l y s i s o f b l o o d . Mgm./ 1 0 0 cc , Erythrocytes G CE Cl N. P. N. UN. 2 .10 400 106.00 55. 30 Normocytic Some p o i k i locytic, hypochromic. Normocytic; some n u c l e a t e d U o o 41.66 15.00 0 .1 2 0 .2 0 480 2 5 .0 0 20.00 2 8 .0 0 0.70 0.60 400 35. 80 30.00 5?Q 460 67.00 16.00 39. 00 1 .1 0 0.80 0.80 rw . o n— 1.78 1 . 65 560 162.00 108.00 115.00 4.16 3.76 550 1 18. 50 98.00 97.50 77.77 1 .1 0 1.00 0.70 430 380 34.00 15.00 1 1.20 0.50 I—1 1.65 420 2 1.00 | 1.30 460 4 1. 00 28. 30 350 30.00 18. 20 170.00 S. 60 9.90 o -v j • 2 0 0 .0 0 11.20 o ia . o 3.1? • 75.55 74.44 I 38.75 ?. 60 j 1.15 L ,. G..............................Gl u c o s e U ............... .......... U r i c a c i d C e ........................... C r e a t i n i n e C l ........................... C h l o r i d e N, P . N.................... N o n - p r o t e i n n i t r o g e n UN........................... Ur e a - n i t r ogen Diagnosis Staphylococcic infection Navel i n f e c t i o n Na v e l i n f e c t i o n , etc. ii Normocytic; few p o i k i l o c y t e s Microcytic hypochromia; poikilocytic Normocytic Some c r e n a t e d & poikilocytic Marked poikilocytosis Microcytic hypochromia; some n u c l e a t e d Normocytic ii Wh i t e m u s c l e disease Wh i t e m u s c l e disease, etc. Docking i n f e c t i o n Acute Meningitis Acut e peritonitis Br o n c h o p n e u m o n i a & encephalitis Br onc hopneumoni a , and,, c o n s t I p a t i p n , : -3?B• ( a ) Tec h n i c Th e Banter i o lo g i c a l of c u l t u r i n g lamb was k i l l e d (or s k i n n e d and o p e n e d which w i l l were according cultured made, for If gross le sio n s was also c u ltu re d In order effective to present, the left diaphragm atic Trie n e e d l e made order w ith A rig h t's A fter the seared, a pair remove a. s m a l l on a n o t h e r tion to get on o n e - t h i r d liver. were bore seared, the from t h e stain deeply lesions sterile piece scissors of t i s s u e Smears fo r surface the sever liver was the of at tw isted as blood. 1 s t i t ks were one Grain's An in­ The s m e a r slides, but follow s: as w e l l from th e to be s t a i n e d stain. spleen had been a n d f o r c e p s w e r e used, t o and a d i r e c t s ame b l o o d - a g a r prelim inary prepared. into plate. of sim ple A sterile m aterial a portion as which i t other w ith a sear the liver. two c l e a n and the of stated a n d im e d i a t e l y least surface smears, to after liver o n e - t h i r d of th e also and and u s e d of a blo o d -ag ar on a t of m aterials as a r o u t i n e . m aterial of the was u s e d t o was w i t n d r a w n l i v e r was made the lobe s p o t w nich had been around in of the and h e a r t - b l o o d from t h e s e exam ination the procedure exam ination spleen wa s d e v i s e d w h i c h i s a u t o p s y - k n i f e was h e a t e d the liver, cultures old o cu latin g needle autopsy and s m e a r s made. make s u c h technic usual and sm ears bacterial b a c t eria.. a. d e a d c a r c a s s ) , A careful and th e were and i s o l a t i n g as to the later. bacteria made f o r p r e l i m i n a r y organs b ro u g h t in be d e s c r i b e d c a r c a s s was t h e n met h o d s . s m e a r w a s made plate bacteriological used for examina­ The h e a r t - b l o o d w a s c u l t u r e d u s i n g The v e n t r a l surface p i p e t t e with the right of the a pointed auricle in h e a r t was the fo llo w in g seared, and a s t e r i l e end was p u s h e d t h r o u g h t h e order to get a sm all w a l l of amount of blood a n d a s m e a r w a s made on t h e rem aining one-third, of blood-agar spleen). At t h e plate (liver and d r o p o f b l o o d w a s l ased t o t h e s e were stained prepare fo r the smears prelim inary technic same the same tim e, a on s l i d e s and bacteriological exam ination. The g r o s s i ng- t h e l e s i o n s were surface. used for a scissors of the affected the glass flu id tissue the the incubated at made daily visible were left for 3?°C. a pyogenic: process remove a s m a l l p ie c e was olood-agar firm . plates S m e a rs from as w e ll a s on anaerobic m icro-organism s, boiled fo r fifteen for were made, 2 4—48 h o u r s bacterial room t e m p e r a t u r e to isola.te following: p ro c e d u re bacterial n e e d l e was l e s i o n s was t r a n s f e r r e d cultures were In o rd e r by s e a r ­ into m inutes deep and agitation. ail at from lesion For c u l t u r i n g b r o t h w h ic h had b e e n A fter the if culturing a sterile were u s e d to from v a r io u s cooled w ithout either exudate w e r e made o n slides. m aterial brain the and f o r c e p s such m a te r ia ls clean A fter t h a t , getting or prepared fo r growth for bacteria was free follow ed. c o l o n i e s w e r e made blood-agar plates and o b s e r v a t i o n s a f t e r which they s e v e ra l days. g r o w t h w a s o b s e r v e d on t h e s m e a rs from t h e the from c o n ta m in a tio n , Whenever v i s i b l e blood-agar and plates, stain ed w ith Gram's -34stain in order pure. If the single colony was t r a n s f e r r e d the to c u l t u r e was c u l t u r e was few c u b i c until determ ine a pure pure a mi xed. , centim eters hours, and. t h e again. in The if every th r e e weeks or cultures were c u l t u r e wa s contam inated, nutrient a slant. If If the pure culture at culture found to be was con­ p l a t e s were 37°C. for pure, they rechecked s o m e t i m e s two w e e k s 24 was p e r f o r m e d were k e p t In m ain tain in g w a s made a n d a and. p l a t e d blood-agar cultures. a transfer broth incubated for as s to c k cultures, the a blood-agar original c u l t u r e s were stock By u s i n g the transfers a refrigerator showed s p a rs e onto was o b t a i n e d . exam ination the and n o t sterile t a m i n a t e d and w o r t h l e s s , discarded. or not a s m a l l p o r t i o n was d i l u t e d w i t h of culture whether for such once f o r those which growth. th e methods and 7 a n a e r o b i c lambs throughout ( b ) B nc t ex io and t e c h n i c s c u l t u r e s were the p e rio d of t h i s described, isolated 41 a e r o b i c from p a t h o l o g i c a l study. logical te s ts . s - Pr e p a r a t i o n of m edia. Most of th e m e d ia were p r e p a r e d a c c o r d i n g ’ t o t h e Manual o f M ethods f o r P u re C u l t u r e „ 2 Study oi b a c t e r i a , M o d i f i c a t i o n s of me d i a , p r e p a r a t i o n w i l l ue d e s c r i b e d , and m a l t o s e , li'cn all the media were 15 po u n d s pressure iusted approxim ately to pH 7 . 0 - 7 . 1 i ’o r as sterility exception ed from each l o t s t e r i l i - 0 . 5 $> ( 1 . 1 % f o r the the b a s a l medium, brom c r e s o l dextrin and m a l t o s e may be b r o k e n down t o the autoclave, these by cold f i l t r a t i o n . (dextrin purple sim pler two tubing, as are forms substances the rare and a u t o c l a v i n g indicator. co m p le x compounds which by h i g h were The n e e d e d a m o u n t or m a lto s e ) •-. cold f i l t r a t i o n , o t h e r s w e r e made by a d d i n g t h e as u su a l w ith substance inulin, fructose, as the su b stan ces) to Since dulcitol, The y w e r e O f -t-ires-e 1-8 me d i a - , S&~ o f - t h e m { d e x t r i n - a n d were all m edia. prepare tem perature specially in prepared of ferm entable was c a l c u l a t e d , d isso lv e d in -378 certain amount of d i s t i l l e d w a t e r a sterile formed, B erkefeld f i l t e r . and a t medium w i t h If satisfactory, tion basal after the it the purple sterility ma k e which a n o th er indicator test a 0.5 of per sterility substances test through was p e r ­ basal ferm entation was t u b e d a n d the was a d d e d a s e p t i c a l l y medium t o The f e r m e n t a b l e The s t e r i l i t y same t i m e brom -cresol autoclaved. tubed the and f i l t e r e d to cent test were u s e d filtrate the proved sterile final concentra­ wa s m a d e . in the follow ing concentrati o n s: Arabinose D extrin D ulcitol Fructose G alactose Glucose G lycerol Inositol Inulin .1 p e r c e n t " " .1 " " .1 " 11 .1 11 " .5 " " .1 " " .1 " " .1 " 11 Litmus m i l k . to L i t m u s m i l k was freshly-separated obtained. Lactose M altose M annitol R affinose S alicin S orbitol Sucrose Trehalose Xylose .5 mediumi n f l o w i n g four days. D u r i n g ; war m w e a t h e r , medi um i n the a suitable refrig erato r steam f o r it between G e l a t i n medium. (for " " " oy 30 m i n u t e s d a i l y was n e c e s s a r y t o p l a c e second h e a t i n g . Formula 11 11 c o l o r was then tu b e d and s t e r i l i s e d p la c in g the the cent " " " p r e p a r e d b y a d d i n g l i t m u s powder skimm ilk u n t i l The m i l k w a s .5 per .5 " .1 " .1 " .1 " .1 " . 5 11 .1 " .1 " 400 c c . ) G e l a t i n ....................................................................2 . 0 g . T r y p t o s e ( B a c t o ) ............................................4 . 0 g . N a ^ H P O ^ ................... 0.75 g . G l u c o s e ...................................................................0 . 40 S o d i u m t h i o g l y c o l l a t e ............................. 0 . 4 0 B e e f e x t r a c t . . .............................................0 . 8 0 D i s t i l l e d w a t e r .........................................4 0 0 . 0 0 g. g. g. cc. the first and for Procedure. autoclaved Me d i u m f o r Formula The i n g r e d i e n t s w e r e dissolved, tubed, end as u su a l. HpS p r o d u c t i o n . (for 400 c c . ) L iv e r in f u s io n (Huddleson, 1 9 3 4 ) POO c c . ■ D i s t i l l e d w a t e r ........................................................................................POO c c . W i t t e ' s p e p t o n e ...................................................................................... 4- g . NaCl P g. Procedure. The l i v e r i n f u s i o n was heating for 1.5 hours in grease free ing beef liv er through a. w i r e mixed w ith other dissolved, tubed, Me d i um f o r Formula indole (for flow ing in 500 c c . screen. necessary and prepared f i r s t steam of POO c c . 1 lb. ta p water of ingredients the and th e m i x t u r e was sterilized. form ation. Same a s f o r (for g. g. g. gs-; g. P50.00cc. p r e p a r i n g g e l a t i n medium. reduction. 500 c c . ) B a c t o - t r y p t o s e . . ............................................................ 1 0 . 0 N a p H P 0 4 .................................................................................. 1.0 G l u c o s e . ............................................................................... .. 0.5 A g a r ...................... ..................................................................... 0 ,5 O 0 3 .......................................................................................... 0.5 B e e f e x t r a c t ....................................................................... 3.5 D i s t i l l e d w a t e r ................................................................ 5 0 0 . 0 Procedure. Same as f o r and and f i l t e r ­ P50 c c . ) Med i u m f o r n i t r a t e Formula fresh i n f u s i o n were B a c t o - t r y p t o n e ...................................................................... 5 . 0 Wa^HPO^....................................... ...............................................0 . 5 G l u c o s e ..........................................................................................0 . P 5 /r. hr'-:". r.or . rrf . ".""T' or. ; p:0 ;p5 B e e f e x t r a c t ............................................................................1 . 7 5 D i s t i l l e d w a t e r ............................................... Procedure. of by preparing g e la tin g. g. g. g. g. g. cc . medium. N utrient broth. procedure The f o l l o w i n g was the ferm entation s ame a s form ula that used was u s e d , for preparing basal medium. B e e f e x t r a c t ...............................................................0 . 5 p e r " N a C l ................... .................................................................0 . 5 P e p t o n e ( D i f c o ) ...................................................... 1 . 0 " D i s t i l l e d w a t e r ................... ................................ o . s . P o t a t o medium. this into Several cleaned, follow ed These about 5 cm. were th e n of NapCogfor changes of d i s t i l l e d was p l a c e d at the treated potato by t h e addition w ater. bottom about placed cc. aqueous and w ash ed i n A glass rod solution several cm.) t e s t - t u b e , and th e into of the test-tube distilled w ater. follow ed These st.e,r.ili.ze..d,' ■, autoclave. St a r c h - a g a r p lates. Formula, ( f o r 400 c c . ) Beef e x t r a c t 2.8 P e p t o n e ................................................................................. 2.0 6.0 A g a r ......................................................................................... Starch ( s o lu b le ) 0 .8 D i s t i l l e d w a t e r ............................................................ 4 0 0 . 0 Procedure. usual, knife. ( 2 cm. x 0 . 3 t u b e s , w e r e , i m m e d i a t e l y . . . . p l u g g e d , wi t h . . . c o t t o n in the cut in diam eter, an o r d i n a r y a dilute of each 1 b o r e r t h e y were and. 1 . ? cm. soaked in s l a n t was of cork each w ith 30 m i n u t e s preparing sound p o ta to e s were c a r e ­ long oy d i a g o n a l c u t t i n g slants (1:500) good-sized a n d oy m e a n s o f a cylinders, cent " " 3} i • \ k 4 : nfi v f;-;} L v ■/ ;• l. i ' . r; 11 " 11 hr ( ■) ’' / . • r ( ) V;'; i.’-'. i [ ; -■ ) Y l; i l l ( ( ( i :) v e -e 7 c ■:•• V;-;V; 71’ i':.l. ;; ( ill O ’! ;v ) I;-;) (:;■/) O 'O (» D (:-) ■ . ;s: ]\f : : t :M 1 0 0 i. •- ; 11-r i ;. r-r . r . . I.'JTii.'. " + ' i 11 \ - - 7 4 ) 1L 7 L) 1 ;• V -v!L: . ; ■: i t ' v) 71-.3H ( ; o ! ... ( " r-0 TrV--f 0 0 •}\ \ :-r- v T •r t r 1 1 ^ ; ; - i i - r. I - f f L i. i i : J. r ± r * 4‘ 4. f -i- L (. - ... j. i- 4 - iur.t Kiji.t _ - „ - „ - i X 4 44 - - -t I - 4. - - j. _ h r • i' t blcoci Li; • r r•■>:■r.t liv e r »ri*\ r'1 corn L t. ' " 1- 4 L ■t 4 ' " F - V r 7 4 4 :*k 4 •t b 4 7 47 4 c 7 4-5? a (re ) - T- h t (rM ( ? f) ! 74n4 i ♦ ~ L "O <'JV. 747 7 r (IT _ \ - 1: ( i-1 ) ( ' !•) - - + -t >v 7:v7 Tr - (4 - !■ .. _ 1 7 !T ) - (-i- {r (V 6F (•1 1 ) 7 4 7" - G i';i :: tiv ,- -t ( ; ti ! - 1 7 47 7 a 74 4? 4 ' (T i) s) - 4 £ t i J '1r ( .1 r •i r L - ' I ■■ . F I. t T- v •; ■’ 4 7 47 4 7 4 0 -, •[ - - ( 1 b) ! ■r.\ \ v» - i • ......... - _ - C 4 _ - - C~-’l i i. .-'C J rr ii. T r . E x p l a n a t i o n of the (l) (p) f i g u r e s u s e d i n Table ( 4) G elatin l i q u e f a c t i o n , indole p ro d u c tio n , m o t i l i ty p e l l i c l e f o r m a t i o n , and s t a r c h h y d r o l y s i s : 4 ....................... .. positive te s t - .............................. n e g a t i v e t e s t EpQ p r o d u c t i o n , h e m o l y s i n p r o d u c t i o n ; test, ^ ..................m a r k e d i .............................. s l i g h t * ..............................v e r y s l i g h t - ............................. n e g a t i v e ( 3 ) Se di me n t a. t i o n , t u r b i d i t y : ^ .............................. m a r k e d i .............................. m o d e r a t e T .............................. s l i g h t t* /- . v n r • , . . « ry ”1 4 4* s j _i_x cl *.k u (4) Pot a t o me d i u m : B” .............................. g r o w t h and br o wn p i g m e n t M .............................. g r o w t h and c r e a m e r y c o l o r Y ................................g r o w t h and y e l l o w i s h p i g m e n t - .............................. n o g r o wt h (5) Litmu s m i l k : a ...............................a c i d b ...............................b a s i c c .............................. c o a g u l a t i o n r ............................... r e d u c t i o n d .............................. d i g e s t i o n g .............................. g a s f o r m a t i o n (o) F e r m e n t a t i o n t e s t s : + . . . .. . co mp let e change t o y e l l o w c o l o r (marked a c i d ) i ............................... p a r t i a l c h a n g e t o y e l l o w c o l o r (moderate acid) z f ...............................s l i g h t l y a c i d (4) marked a c i d w i t h gas p r o d u c t i o n (1 ) moderate a c i d with gas p r o d u c t io n ( * ' ............................s l i g h t l y a c i d w i t h g a s p r o d u c t i o n H t > ............................ r e t u r n e d t o b a s i c r e a c t i o n B ............................ b a s i c r e a c t i o n From T a b l e (4), i t w i l l be n o t e d t h a t 41 c u l t u r e s i s o l a t e d from v a r i o u s p a t h o l o g i c a l c a s e s were s u b j e c t t o b i o c h e m i c a l tests, and, as a r e s u l t , 7 g en er a of b a c t e r i a , were i d e n t i f i e d and 2 c u l t u r e s , were u n d e t e r m i n e d . Trie i d e n t i f i e d genera (7 ) included: Staphylococcus, Escherichia., Bacterium, Di-*plococcus, N e i s s e r i a , Pasteu.rella, and Corynebacterium , w h i l e t h e u n d e t e r m i n e d o n e s w e r e a g r a m - p o s i t i v e c o c c u s and a gram-negative frequency, coccoid c a c i l l u s . In r e s p e c t to t h e i r B a c t e r i u m was i s o l a t e d f r o m 11 c a s e s S t a p h y l o c o c c u s from 8 c a s e s ( 1 9 . Pfo), P a s t e u r e l l a ( P 6 . 8 $>), from 6 c a s e s ( 1 4 . ?fo), D i p i o c o e c u s and C o r y n e b a c t e r i u m from 5 c a s e s e a c h (lP.P%), E s c h e r i c h i a from 3 c a s e s p o sitiv e coccus, 1 c a s e each (?.3fo), N e i s s e r i a , and g r a m - n e g a t i v e c o c c o i d b a c i l l u s gram from (P Besides t h o s e c u l t u r e s .just m e n t i o n e d , 5 c u l t u r e s of A c t i n o m y c e s n e c r o p h o r u s a nd P c u l t u r e s o f C l o s t r i d i u m w e l c h i i w e r e i s o l a t e d f r o m v a r i o u s c a s e s and c u l t i v a t e d i n dee p - b r a i n b r o t h . -46- c • Pathogenicity te a ts . Preparation of i n o c u l u m . inoculated d ire c tly from t h e b r o t h and i n c u b a t e d a t 37° G. The m i c r o - o r g a n i s m s we r e stock c u l t u r e s i n t o n u t r i e n t f o r 24 h o u r s . t u r e s wer e t r a n s f e r r e d t o 1 5 c . c . centrifuged (^orvall centrifuge) minutes u n t i l The b r o t h c u l ­ centrifuge at t u b e s and 41413 r . p . m . for 20 t h e s u p e r n a t a n t f l u i d was c l e a r a n d c o u l d be discarded into a beaker by i n v e r t i n g ; t h e t u b e s w i t h o u t d i s t u r b i n g the bacteria collected at w e r e wa s h e d t w i c e w i t h s t e r i l e salt the solution and re—s u s p e n d e d t o g i v e a t u r c i d i t y tuDe-antigen fo r Inoculation bottom. the The b a c t e r i a ( 0 , 8 5 $ NaCl) same a s t h e standard the B ru c e lla a g g lu tin a tio n t e s t . of e x p e r i m e n t a l a n i m a l s . and m i c e w e r e u s e d f o r t h i s test. Both r a b b i t s They w e r e h o u s e d i n c l e a n w i r e - m a d e c a g e s a nd f e d w i t h o r d i n a r y r a t i o n w i t h a n ampl e supply of w a te r . during a p r e lim in a r y p e r io d of a t l e a s t one ,week b e f o r e t h e . t e s t , t h e . a n i m a l s we r e c h e c k e d f o r h e a l t h and a l l t h e u n h e a l t h y ones were d i s c a r d e d . The mouse was h e l d by t h e t a i l o f an a s s i s t a n t . The r i g h t a nd h e a d w i t h t h e a i d side of the s wa b b e d w i t h 7 0 $ a l c o h o l a n d 0 . 5 c . c . l o w e r abdomen was of the suspended i n o c u l u m was i n j e c t e d i n t r a p e r i t o n e a l l y w i t h a. s t e r i l e 1 .0 cc, h y p o d e r m i c s y r i n g e h a v i n g a 26 g a u g e n e e d l e . mouse o u t o f e v e r y f i v e was i n j e c t e d w i t h 0 . 5 c . s t e r i l e 0 . 8 5 $ NaCl s o l u t i o n t o s e r v e m i c e wer e k e p t c. as a c o n t r o l . One of Two i n one c a g e w i t h one o f t hem h a v i n g t h e t i p o f -47one e a r c l i p p e d for id e n tific a tio n . l a b e l e d and a l l t h e mice were o b s e r v e d t h r e e t i m e s d a i l y for signs of i l l n e s s or d e a t h . The r a b b i t t o be i n j e c t e d was c o n f i n e d i n a wooden box w ith the head f r e e . One o f t h e e a r s was m o i s t e n e d w i t h 70 p e r c e n t a l c o h o l a n d 2 c . c . were i n j e c t e d intravenously Two r a b b i t s w e r e the The c a g e was c a r e f u l l y of t h e suspended b a c t e r i a in to the marginal ear vein. p ut t o g e t h e r i n one c a g e w i t h t h e h a i r on back o f one o f them c l i p p e d t o s e r v e f o r i d e n t i f i c a t i o n . The c a g e was l a b e l e d a s u s u a l and t h e o b s e r v a t i o n s made u n d e r t h e same c o n d i t i o n a s f o r t h e m i c e . Technic o f c u l t u r i n g ti s s u e s of experim ental an im als. I f the experim ental r a b b i ts t h e y wer e k i l l e d f i v e However, pathogenicity te s ts , (30 c . c . syringe) in­ through the ^a.ch r a b b i t was t h e n a u t o p s i e d a n d t h e t i s s u e s c u l t u r e d using the lambs. the d a y s a f t e r i n o c u l a t i o n by t h e t r a v e n o u s i n j e c t i o n of a i r marginal ear v ein , survived same t e c h n i c t h e r a b b i t s we r e n o t as employed f o r th e skinned. I f t h e e x p e r i m e n t a l m i c e s howed no sympt oms and s u r ­ vived the p a th o g e n ic ity t e s t s , after they were k i l l e d i n o c u l a t i o n by g r a s p i n g t h e t a i l f i v e days o f e a c h mouse w i t h a p a i r o f l o n g f o r c e p s and h i t t i n g t h e h e a d on a c e m e n t f l o o r . As s oo n a s t h e y w e r e k i l l e d , e a c h wa s s t r e t c h e d on a p i e c e o f wooden b o a r d w i t h t h e a i d o f f o u r t h umb t a c k s . was t h e n s k i n n e d , opened, a n d c u l t u r e s made f rom t h e l i v e r u s i n g t h e same m e t h o d e m p l o y e d f o r c u l t u r i n g t h e p a th o lo g ic a l lambs. The mouse t i s s u e s of However, i n c u l t u r i n g the h e a r t - b l o o d . -48snci s p l e e n o f m i c e , t h e f o l l o w i n g p r o c e d u r e s wer e f o u n d t o be more a p p l i c a b l e . The v e n t r a l s u r f a c e s e a r e d as u s u a l . A sterile grasp the sid es of the h e a r t o f t h e h e a r t was p a i r o f f o r c e p s was u s e d t o and by s q u e e z i n g t h e forceps a d r o p o f b l o o d woul d u s u a l l y ooze f r o m a h o l e made i n t h e middle of the s e a r e d s p o t w i t h the a i d of a s t e r i l e h a v i n g a s m a l l and p o i n t e d l o o p a t t h e b l o o d was o o z i n g o u t , tip. needle s o o n as t h e t h e n e e d l e was i n t r o d u c e d - i n t o t h e h e a r t i n o r d e r t o g e t a g o o d s i z e d d r o p o f b l o o d w i t h whi ch to s me a r o v e r 1 / 3 o f a b l o o d - a g s r p l a t e . The s p l e e n was c u l t u r e d by s e a r i n g an a r e a n e a r e i t h e r end (p re fe ra b ly the v e n t r a l end). A sterile needle (the same n e e d l e u s e d f o r c u l t u r i n g h e a r t - b l o o d . ) was i n t r o d u c e d through the se a re d area i n t o axis. Since t h e the s p l e e n along i t s s u o t e r m i n a l p a r t of t h e and c o n s e q u e n t l y we a k e n e d , it long s p l e e n was s e a r e d was e a s y t o i n t r o d u c e - s t- e r iI © n e e d l e "'through' th e - we-ak e n e d - s p o t i n t o - t h e the spleen-' ™-- pulp in order to secure s u f f i c i e n t m a t e r i a l f o r p l a t i n g . T h i s p r o c e d u r e was f a c i l i t a t e d by g r a s p i n g t h e e x t r e m e end of the spleen w ith a p a i r of fo rcep s. I d e n t i f i c a t i o n o f b a c t e r i a . i s o l a t e d f r om e x p e r i m e n t a n i m a l s . The b a c t e r i a i s o l a t e d f r om r a b b i t s and mi c e w e r e s t a i n e d and t h e b i o c h e m i c a l t e s t s w e r e made w i t h Glucose, l a c t o s e , medi um, sucrose, starch-agar plate, glycerol, the f o l l o w i n g media: NOg b r o t h , litmus milk, indole and g e l a t i n . a c t i o n s o f t h e m i c r o - o r g a n i s m s i n t h e s e m e d i a and t h e The r e ­ -49characteristics u po n s t a i n i n g were c o m p a r e d t o t h o s e o f t h e o r i g i n a l c u l t u r e s i n o r d e r t o check t h e i r i d e n t i t y . R esults of p ath o g en icity are arranged in Taole (5). test. The r e s u l t s of the t e s t "50Ta.ble ( 5 ) . Culture Jio. 730 8 7334 7335 7336 7 33 7 Results of T e s t Mouse "“R a b b it. X X X X 7 344 73 50 73 51 7353 7358a 7 3 5 8b 7353c 7 36 Pa 736?b 7 36 Pc 736 5 7 371a 7371b X X X X X — — 7415 7 443 7 460a 7 460b 7 460c 7 47 4 Tot a l ; 41 X _ — 7 3 38 737 Pa 7 379b 737 3a 7373 b 7 373c .739 3 a 7393b 7393c 739 4 a 7 39 4b 7 400 7 401a 7 401b 7 401c 7 40 6 7 410 Result s of P a th o g e n ic ity Tests. X — _ _ — — - — — — X X X X H.L.S. H.S. L.S. S . ( contaminated)* H.L.S. H, H.S. H.L.S. H.L.S, H. L. H.L.S. H.L.S. H. S H.L.S. — S. X — "*"X ... . — — — '■'"L."S'." ™ .............. .*. H.L.S. H.L.S. H.L.S. — — H.L.S. X died in died in died in died in died in 30 h r . P8 h r . 38 h r . 60 h r . 24 h r . * * H* * * Died i n 3 8 h r . * * m X * ..' ..... ..■ Mouse d i e d Mouse d i e d Mouse d i e d ★ * D i e d i n PP ... " ■ i n 14 i n 15 i n 18 "... ................. ..' *“ hr. hr. hrs. hrs. X — — X Mouse Rabbit Mouse Mouse Mouse X X V * Mouse d i e d i n 1 5 h r . 11 " " P I h r . , r a b b i t i n 24 " v e r y s i c k , k i l l e d i n 40 h r . * * — X X Remar ks bacteria Recovered f r om — — H.L . P . S . L.S.(contam­ i n a t e d) * Mouse d i e d i n * 4 days. * — — - — — — * X L.S. X (contam­ inated) 2 5( i n e luding 1 3 ( mi c e be c a me v e r y s i c k o r d i e d 3x 20x contaminated w i t h i n 4 days a f t e r i n o c u l t a i o n . ones) Note: E x p l a n a t i o n of t a b l e . x .................. * . p o s i t i v e t e s t H ..................... H e a r t b l o o d P. . . . P e r i t o n e a l _ ........................ n e g a t i v e t e s t L .....................L i v e r fluid .............. . . K i l l e d i n S . . .................S p l e e n 5 day s . -5 1T'ne r e s u l t s PO ( 48 . 7 8 %) of the e x p e r im e n t i n ( 5) slowed t h a t o u t o f t h e 41 o r i g i n a l c u l t u r e s w e r e r e c o v e r e d from t h e e x p e r i m e n t a l m i c e , definitely Table virulent. o f w h i c h 13 ( 3 1 . 7 fo) w e r e The s e 13 v i r u l e n t cultures either c a u s e d t h e d e a t h o f m i c e o r made them s e r i o u s l y i l l f o u r days a f t e r inoculation, o f t h e PO p o s i t i v e within while the remaining 7 c u ltu r e s t e s t s d i d n o t i n d u c e any n o t i c e a b l e s ympt oms u p t o f i v e d a y s a f t e r i n o c u l a t i o n a t w h i c h t i m e t h e mice were k i l l e d f o r e x a m i n a t i o n . only 3 p o s itiv e As f o r t h e r a b o i t s , t e s t s we r e o b t a i n e d f r o m PP i n o c u l a t e d a n i m a l s which i n d i c a t e s t h a t r a b o i t s were q u i t e r e s i s t a n t to the c u l t u r e s i s o l a t e d f r o m l a mb s a n d we r e n o t s u i t a b l e for such work. the t e s t animal i n t h is experim ent. were found t o Incidentally, r a b b i t s were f i r s t oe r a t h e r i n d i f f e r e n t u s e d as L a t e r on, when t h e y to the c u l t u r e s , were u s e d i n s t e a d . i mi c e C. P a t h o.. l .o— g>1 i, c a.. ...l M ethods. . - ..................... ( B■ T e c h n i c u s e d f o r autopsy. The l a m b s w e r e e i t h e r the laboratory bled to d e a th or brought for autopsy. In e i t h e r case, dead to th e y were i m m e d i a t e l y s k i n n e d and c a r e f u l l y e x a m i n e d f o r g r o s s l e s i o n s in every p e r t nerves, of th e body, end s o m e t i m e s t h e the b rain , in clu d in g the b ra in , spinal cord. ^ ^ ,, V t/ 4-Vi lo o n o n -f’ liilU WJ region. olunt In o r d e r t o expose a f r o n t a l c u t wa.s made t h r o u g h t h e n a s a l c a v i t i e s e x t e n d i n g : a l o n g an i m a g i n a r y d , c/ u V / -fc. + V .n o *">Y »Q l i n e j u s t below t h e o r b i t s 1 1 ^ + 1 1 *1 + •-* U J .J . u * J . A •» V* O C l p h p H V. w Th e n , by a g e n t l e t i p p i n g and w i t h tip cranial of a p a i r of s c i s s o r s , —v +"VlC5 n P P l - — Vv W — A + 0 and 1 the h e l p o f the a g r e a t e r p art of the b rain ( t h e e n t i r e c e r e b r u m ) was s l i p p e d o u t o f t h e u p p e r h a l f of t h e s k u l l and e x p o s e d , le a v in g the o b lo n g a ta in the lower h a l f . (Fig. c e r e b e l l u m and. m e d u l l a 1, 2) ( D) T e c h n i c s f o r p r e p a r i n g p a t h o l o g i c a l t i s s u e s . ‘ The t i s s u e s were- f i x e d i n - Zenker '-a f l u i d a n d som e- • " tim e in 10$ f o rm o l s a l i n e . drated, They we r e then washed, dehy­ embedded and s e c t i o n e d by o r d i n a r y h i s t o l o g i c a l technics, and f i n a l l y Gram-Weigert, s ta in e d e ith e r with hem stoxylin-eosin, M allory's a n ilin -b lu e , o r by e l l t h r e e m e t h o d s -5 3 P re se n ta tio n of cases Case 7 356 ( G r a d e , m a l e ) T n i s was a t y p i c a l c a s e o f w h i t e - r n u s c l e d i s e a s e o r so-called 11s t i f f - l a m b 11 d i s e a s e . Hi s t o r y . T n i s l amb was o wn e d by Mr. S a v a g e o f A l b i o n , Michigan, and was d e l i v e r e d t o t h e p a t h o l o g y b a r n on 4 / 3 / 4 4 . The l amb was s h o w i n g e v i d e n c e of w h i t e - m u s c l e d i s e a s e and was u n a b l e to r i s e . t h e time of d e l i v e r y would not n u r s e . The a n i m a l made no p r o g r e s s f o l l o w i n g and on t h e m o r n i n g o f A p r i l 4 t h I t was t h e n s a c r i f i c e d and s t u d i e d . lamb was 5 w e e k s o l d . Etiology. Undetermined. No b a c t e r i a w e r e i s o l a t e d f r o m th i s case. Blood s t u d i e s . ( a ) Blood p i c t u r e " Erythrocytes 1 9 , 9 5 0 , 0 0 0 p e r c.mm. L e u c o c y t e s " . . T.". ",'T I T , 600'............... .. H e m o g l o b i n ............... 9 . 8 g./lOO cc. D i f f e r e n t i a l c ou n t (fo) Lymphocytes 7 93 N eutrophils. seg-nenters ( 88) bands ( 4) Monocytes. 1 EosinophiIs 0 BasophiIs. , 0 ( k ) Blood, c h e m i s t r y Glucose Uric a c i d . Creatinine Chloride. . N . P . N ........... Ur e a - N (Mgm/100 c c .) 196.00 1.78 1.65 560.00 169.00 108.00 The -54- From t h e r e s u l t s o f t h e blood s t u d i e s , in g to note t h a t the chem ical a n a l y s i s t h e blood, p i c t u r e of t h i s o f Case No. 7358. it is of b l o o d a s w e l l a s case r e s e m b le d q u ite c l o s e l y t h a t A l l b l o o d e l e m e n t s which had been s t u d i e d were d e c i d e d l y i n c r e a s e d , and y e t on t h e o t h e r h a n d t h e n u mb e r o f l y m p h o c y t e s was v e r y much d e c r e a s e d . neutrophilia was a l s o v e r y p r o n o u n c e d , mature forms. value in normal, In g e n e ra l, the p e c u l i a r but i t The showed m o s tl y feature of increased c l o o d e l e m e n t s s e e m e d t o be Q u i t e u n i q u e wnite-muscle interest­ disease. for The e r y t h r o c y t e s wer e mor e o r l e s s a l t h o u g h a few p o i k i l o c y t e s w e r e o b s e r v e d . Grose l e s i o n s . Sk e l e t a l m u s c l e s . The s k e l e t a l m u s c u l a r i s on b o t h s i d e s o f t h e body w e r e i n v o l v e d , and th e l e s i o n s appeared as su p er­ f i c i a l w h i t i s h patches or s t r e a k s . Li v e r . The l i v e r showed some f a t t y "'•""O t h e r - o r g a n s - . degeneration. ■■■■■■■■•.... .. •Apparently-' n o r m a l . . Microscopic l e s i o n s . Li v e r . The l i v e r was v e r y much c o n g e s t e d and s h o w e d c l o u d y s w e l l i n g end f a t t y w e l l as t h e degeneration. Most b l o o d v e s s e l s as s in u s o i d s were d is te n d e d with blood. d e g e n e r a t i o n was r a t h e r e x t e n s i v e and d i f f u s e , 8t the c e n t r a l p a r t presence of f a t were e i t h e r beginning of each l o b u l e and e x t e n d i n g g r a d u a l l y in a dim inishing gradation affected c e lls The f a t t y t o w a r d -the p e r i p h e r y . The became g r a n u l a r and v a c u o l a t e d d ue t o t h e globules in the cytoplasm, and t h e n u c l e i p u s h e d t o one s i d e o r we r e p y k n o t i c . - 55- Kidneys. The k i d n e y s w e r e r a t h e r c o n g e s t e d a n d showed e v i d e n c e of c lo u d y s w e l l i n g , hemorrhage. d e g e n e r a t i o n and The c o n v o l u t e d t u b u l e s w e r e g e n e r a l l y some­ what. d i l a t e d , capsular fatty and t h e l u m i n a t o g e t h e r w i t h t h e sub- s p a c e s wer e f i l l e d w i t h v a r y i n g a m o u n t s o f d e b r i s and h y a l i n e c a s t s . The e p i t h e l i u m o f some c o n ­ v o l u t e d t u b u l e s wer e a f f e c t e d by m a r k e d f a t t y the condition degeneration, being e s p e c i a l l y pronounced in th e p o r ti o n of th e proximal convo luted tu b u l e s . terminal Occasionally, some i n t e r l o b u l a r p e t a c h i a e wer e o b s e r v e d and some d i s ­ i n t e g r a t e d e r y t h r o c y t e s were p r e s e n t i n th e c o l l e c t i n g tubules. Skeletal m uscle. In t h i s m u s c l e s w e r e more o r l e s s case, quite involved. a numDer o f s k e l e t a l Se ve n b l o c k s o f m u s c l e wer e t a k e n from v a r i o u s a r e a s o v e r t h e microscopic study. Dody f o r The g e n e r a l c h a r a c t e r i s t i c s of the -lesion,..were m o r e o k - l e s s the...,same.namely,,.. myodegenera-tion f o l l o w e d by e i t h e r m y o - r e g e n e r a t i o n o r f i b r o s i s . Case No. 7 3 5 8 ) . ( See a l s o The d e g e n e r a t i v e c h a n g e s o f t h e m u s c l e wer e c h a r a c t e r i z e d by a d i f f u s e a n d f r a g m e n t a r y n e c r o s i s w i t h some f i b r o b l a s t i c fib e rs generally The a f f e c t e d m u s c l e became s w o l l e n and wavy, t r a c t i o n or shrinkage pieces. activity. f o l l o w e d by c o n ­ and c o n s e q u e n t l y b r o k e i n t o small As s o o n a s t h e m u s c l e f i b e r s b r o k e i n t o p i e c e s , some o f t h e more s e v e r e l y a f f e c t e d o n e s u n d e r w e n t h y a l i n e 13 or Z e n k e r 's d e g e n e r a t i o n . ( F i g . 3 , 4 ) Th e s e d y i n g m uscle-fi oers l o s t their characteristic s t r i a t i o n s and -55- nuclei and became more o r l e s s c o a g u l a t e d . stained e ith e r pinkish They w e r e or dark p u r p l e w i t h h e m a t o x y l i n - e o s i n a n d some o f them a p p e a r e d t o c o n t a i n a c e r t a i n kind of d e p o s i t . (Fig. 4, 5, 6 ) . I n some i n s t a n c e s , nowever, the d e s t r u c t i v e p r o c e s s was n o t so s e v e r e only the s a r c o p l a s m was h y a l i n s t e d w h e r e a s t h e s a r c o l e m m a w i t h t h e n u c l e i was r o t affected. Following the degenerative changes, p r o c e s s was g o i n g o n . f e a t u r e wa s p r o l i f e r a t i o n blastic and t h e n u c l e i or sarcolemrnae. a regenerative In t h i s r e g e n e r a t i v e p r o c e s s , t h e most s t r i k i n g cells of th e f i b r o ­ of u n a f f e c t e d muscle f i b e r s Occasionally, a few p o l y m o r p h o n u c l e a r l e u c o c y t e s and p l a s m a c e l l s wer e o b s e r v e d . blastic and The f i b r o ­ p r o l i f e r a t i o n r e s u l t i n g i n f i o r o s i s was t o strengthen t h e weakened a r e a s . The n e w l y - f o r m e d n u c l e i f r o m t h e n o r m a l m u s c l e f i b e r s or s u r v i v i n g sarcolemrnae mi_gra;t ed._ towards,..'the i n j u r e d ends. and. .each. u .a rn le d „a ■s m a l l amount o f s a r c o p l a s m and t r a n s f o r m e d e i t h e r i n t o muscle giant c ells muscle f i o e r s . or directly into regenerating The n u c l e a r p r o l i f e r a t i o n and c e l l w e r e so e x t e n s i v e t h a t i n c e r t a i n w h i c h ha.ve b e e n r e f e r r e d division s p o t s a g r e a t mass of such newly-formed c e l l s were p r e s e n t , P7 Waldeyer ' . gradually (Fig. 4, 9, 11, t o as" M u s k e l z e l l e n s c h l & u c h e " ip) , of The f o r m a t i o n o f s u c h s t r u c t u r e s h a s b e e n t h e s u b j e c t o f much d i s c u s s i o n s i n c e e a r l y h i s t o r y o f m e d i c a l 1 3 , 2 6 , 2 7 , 28 , 37 science. I n f a c t , some o f t h e s e n e w l y formed c e l l s were r e g e n e r a t i n g m uscle f i b e r s w h i l e o t h e r s ■ -57- were muscle g i a n t - c e l l s . The f u n c t i o n o f t h e m u s c l e g i a n t c e l l s was t o r e mo v e t h e dead muscle tissue and t h a t o f t h e r e g e n e r a t i n g m u s c l e —f i b e r s was t o f i l l t h e g a p s l e f t Dv t h e d e a d t i s s u e s . I n Q u i t e a n u mb e r o f i n s t a n c e s , the w r i t e r was a o l e t o d e m o n s t r a t e a m u s c l e g i a n t c e l l e n ­ gulfing a piece (Fig. 7, 7a., of de ad muscle of c o n s i d e r a b l e 8, 9 ) , while size i n a n o t h e r he f r e q u e n t l y en­ c o u n t e r e d s e v e r a l s u c h g i a n t - c e l l s e a c h c o n t a i n i n g one o r s e v e r a l food vacuoles f i l l e d w ith sm all p ie c e s of t i s s u e debris (Fig. 12, 10). Therefore, i n such c s E e s , the f u n c t i o n o f m u s c l e g i a n t - c e l l s was b e a u t i f u l l y i l l u s t r a t e d . T h e s e g i a n t - c e l l s wer e s o a c t i v e shape. like t h e y h a d no d e f i n i t e They somewhat r e s e m b l e d amebae and a c t e d a l m o s t them. The c e l l s u s u a l l y t h r u s t bodies in o rd e r to e n g u lf (Fig. that 7, 7a, rounded, t h e dead m u s c l e t i s s u e As s o o n a s t h e d ig e s tio n began. muscle fiber' removed, 8, 9 ) . out p a r t s of t h e i r d e a d t i s s u e wa s s u r ­ G r a d u a l l y t h e p i e c e s of dead diminished in size u n t i l they were com pletely l e a v i n g food v a c u o l e s b e h i n d ( F ig . 11). After t h e d e a d t i s s u e was c o m p l e t e l y d i g e s t e d and a b s o r b e d , the f o o d v a c u o l e s d i s a p p e a r e d and t h e g i a n t - c e l l s w e r e t h e n ready to r e p e a t t h e amazing: p r o c e s s (Fig. 19). These m u s c l e g i a n t - c e l l s w e r e f o r m e d e i t h e r by f u s i o n of the newly-formed r e g e n e ra tin g c e l l s m ito sis without cytoplasmic div isio n i o r m e t i o n o f g i a n t —c e l l s (Fig. 13, (Fig. 15). 14) o r by The h a s been a l s o a p r o b l e m o f g r e a t -59controversy in the m e d i c a l f i e l d end. q u i t e a n u m b e r o f 07 t h e o r i e s ' - have been f o r m u l a t e d . Some w o r k e r s t h o u g h t t h a t t h e y m i g h t be f o r m e d by c e l l f u s i o n , o t h e r s main­ t a i n e d t h a t t h e y wer e d e r i v e d by m i t o s i s w i t h o u t c e l l division, and s t i l l others in sisted e x i s t e n c e by b o t h f u s i o n t h a t t h e y came i n t o a nd m i t o s i s . S i n c e t h e r e was no ac tu a l c o n c re te evidence to support th e vario us t h e o r i e s , much c o n f u s i o n definite existed. From now o n , it i s hoped th a t the evidence of the fo rm atio n of m u s c le - g ia n t c e l l s i n t h e cs.se o f w r i t e —m u s c l e d i s e a s e may s e r v e a s a s o u n d b a s i s o f t r e n e w—Dorn l a mb s for f u r t h e r in v e s tig a tio n s t o the f o r m a t i o n of o t h e r k i n d s of g i a n t c e l l s c o n f u s i n g c o n d i t i o n , which i s s t i l l particular fie ld , The s i n e as and t h e ex istin g in th is may be u n r a v e l e d . o f t h e m u s c l e g i a n t - c e l l s was v a r i a b l e ; o f t h e l a r g e s t m e a s u r i n g a b o u t 0 . 0 5 mm. X 0 . 0 7 mm. one The n u c l e i " ' w e r e e i t h e r s p h e r i c a l ;n r ' oval - inr ' s h a p e , ' b h t " a i r ' w e r e p r o v i d e d w i t h a h e a v y d i s t i n c t n u c l e a r membrane, nearly c le a r nucleoplasm, defined n u c le o li. f i n e or a n d f r om one t o t h r e e w e l l The number o f n u c l e i v a r i e d a n d f r o m t wo t o t w e n t y - f i v e w e r e o b s e r v e d Their arrangement in the (Fig. 7, 7a, 9, c e l l was i r r e g u l a r 19). and i n d e f i n i t e . I n a s e c t i o n s t a i n e d w i t h a n i l i n e - b l u e end e o s i n , it was o o s e r v e d t h a t t h e n e c r o t i c m u s c l e - f i b e r s w e r e s t a i n e d orange to p u r p lis n -b lu e red, the f i b r o b l a s t i c or blue, tissue t h e normal m u s c l e - f i b e r s blue w i t h s m a l l s p i n d l e - s h a p e d -59- yellowish n u c le i, and t h e r e g e n e r a t i n g m u s c l e - f i b e r s a n d muscle g i a n t - c e l l s grey w i t h c l e a r c o l o r l e s s n u c l e i tain in g yellowish nucleoli (Fig. 6 , 7, 7a, 8 ). c on ­ The regenerating m uscle-fibers generally possessed f a i n t distinct fib rils striations (Fig. and some o f t hem a l s o c o n t a i n e d c r o s s 6 , 8 , 1 1 ) , w hile th e muscle g i a n t - c e l l s we r e more o r l e s s h o m o g e n e o u s i n n a t u r e . aniline-blue and e o s i n s t e i n , the s ta in in g affinity of tissue, By m e a n s o f t h e morphology of n u c l e i both g i a n t - c e l l s g e n e r a t i n g m u s c l e - f i b e r s were e x a c t l y clearly that to and and t h e r e ­ t h e same, indicating t h e y w e r e a l l d e r i v e d f r o m t h e same p a r e n t i.e., muscle, Generally a n d we r e n o t o f e x t r a - m u s c u l a r o r i g i n . speaking, i f m y o d e g e n e r a t i o n wer e n o t too s e v e r e and m y o - r e g e n e r a t i o n f o l l o w e d a c o m p l e t e o r t o t a l restoration case, of the a f f e c t e d muscle i s the myo-regeneration is c a r rie d possible. In t h is o u t by t h e p r o c e s s o f n u c l e a r p r o l i f e r a t i o n f r o m u n a f f e c t e d m u s c l e - f i b e r s or s a r c o l e mr n a e s o a s t o f o r m m u s c l e g i a n t - c e l l s of d e v i t a l i z e d t i s s u e the f i l l i n g fibroblastic in to s u b sta n tia te and r e g e n e r a t i n g m u s c l e - f i b e r s for the gaps l e f t activity f o r the removal is by t h e d e a d t i s s u e . reduced to these f a c ts , a minimum. a l amb r e c o v e r e d In order from "white m u s c l e " d i s e a s e was s l a u g h t e r e d e a r l y l e s t f a l l no l e s i o n s were found w h a t s o e v e r . b o i l e d or f r i e d The (1944) The lamb c h o p s wer e end t a s t e d from normal la m b s. and j u s t a s g o od and t e n d e r a s t h o s e PiQ ... ■ . Mi c r o s c o p i c _1e s i o n s . Round l i g a m e n t o f l i v e r . urnDi l i cum and i t s liver resulted fiorosis. The b a c t e r i a l i n f e c t i o n of the e x te n s io n along the round lig am en t of in n e c r o s i s , suppuration, e r o s i o n , and The i n n e r p o r t i o n o f t h e l i g a m e n t was f i r s t a t t a c k e d and t h e l e s i o n g r a d u a l l y s p r e a d from t h e r e w i t h a zone o f c o a g u l a t e d dead c e l l s , outward a zone o f m a c r o p h a g e s m i x e d w i t h d y i n g p o l y m o r p h o n u c l e a r l e u c o c y t e s , a zone o f dense f i b r o b l a s t i c c e l l s , leucocytes, m a c r o p h a g e s and. p o l y m o r p h o n u c l e a r a. zone o f l o o s e r f i c r o c l a s t i c c e l l s , . ma c r o ph a g e s , p i asm a c e l l s and l y m p h o c y t e s , and f i n a l l y a zone o f fibrosis. Live r . The l i v e r was s omewhat c o n g e s t e d and showed c l o u d y s w e l l i n g and h e m o r r h a g e . The s i n u s o i d s wer e m o d e r a t e l y d i l a t e d and d i s t e n d e d w i t h an e x c e s s i v e number o f e r y t h r o ­ c y t e s and n e u t r o p h i l s . generalized, The c l o u d y s w e l l i n g was more o r l e s s although i t was m i l d i n n a t u r e . Surrounding t h e a r e a s o f h e m o r r h a g e , a. polymorphonuclear l e u c o c y t i c i n f i l t r a t i o n was p r e s e n t . The h e m o r r h a g e s w e r e i r r e g u l a r i n s h a p e and v a r i a b l e i n s i ye. r a n g i n g from a m i n u t e u n ­ l i m i t e d area t o t h o s e of c o n s i d e r a b l e s i z e wnic-h w e r e surr ou nd ed by e thin f i b r o u s w a l l . Lungs. The l u n g s showed l e s i o n s o f s u p p u r a t i v e broncho­ The a r e a s a d j a c e n t t o t h e s u p p u r a t i v e pneumonia. foci wer e i n f i l t r a t e d w i t h pol ymorphonucl ear l e u c o c y t e s w h i l e t h o s e sway f r o m t h e s u p p u r a t i v e f o c i s howed a t e l e c t a s i s o f t h e a l v e o l i , and - ..pr0 nch.opneum.oni.a-.wi t h m a c r o p h a g e i n f i l t r a t i o n . Intestine. The b l o o d v e s s e l s o f t h e i n t e s t i n e were r a t h e r c o n g e s t e d b u t no o t h e r l e s i o n s w e r e a p p a r e n t . Kidneys. Mos t g l o m e r u l i w e r e s w o l l e n and s t u f f e d w i t h an e x c e s s i v e number of p r o l i f e r a t i v e c e l l s p r o l i f e r a t i v e glomerulo-nephrit i s so t h a t a c a s e o f existed. The l u m i n a o f c o n v o l u t e d t u b u l e s w e r e g r e a t l y d i l a t e d and f i l l e d w i t h a considerable amount o f e d e m a t o u s f l u i d m i x e d w i t h some albuminous c a s t s . Trie e p i t h e l i u m o f the c o n v o l u t e d t u b u l e s s howed v a r i o u s d e g r e e s o f c l o u d y s w e l l i n g and some o f t h e c e l l s were d e s q u a m a t e d . - - 9 3- H eart. Just beneath the endocardium, some f a t t y degenera­ t i o n o f t h e my o c a r d i u m wa s n o t e d . J oint cap su le. The j o i n t c a p s u l e o f t h e r i g h t c a r p u s s h o we d t y p i c a l Ot h e r l e s i o n s o f an a c u t e tissues. suppurative arthritis. Apparently normal, Sun many and d i s c u s s i o n . 1 , The a n i m a l s u f f e r e d f r o m n a v e l i n f e c t i o n r e s u l t i n g i n s c s c e s s - f o r m s t i o n end. b r o n c h o p n e u m o n i a o f t h e l u n g e , h e m o r r h a g e s i n t h e l i v e r ; gl o t i ph i ! o—n p n h r i t i s and artbritis, P. T h i s l amo was anemi c a s r e v e a l e d r e d o l o o d c e l l s and h e m o g l o b i n . a t t a c k e d , by a c u t e a r t h r i t i s by t h e l ow v a l u e f o r S i n c e t n i s l a m b was and w a s l a m e , apparently i t d i d n o t g e t e nough f o o d i n o r d e r t o m a i n t a i n i t s binoo l e v e l . --3. ■■■.The-., l e u c o c y t e s i s ..c o u l d b e t h e ' . . r e s u i t " o.f ■v a r i o u s , c o n d i - . t i o n s such as a b s c e s s - f o r m a t i o n , n e p h r i t i s , arthritis, pn e u mo ni a a n d e v e n h e m o r r h a g e s i n acute the l i v e r . P r o Da. o l y , t h e c o m b i n e d e f f e c t o f e l l t h e s e c o n d i t i o n s was t h e r e e l cyte s is in 4. or a c t u a l c a u s e o f s u c h a ma r k e d l e u c o ­ this esse. The h i g h v a l u e s o f a l l olood components ( e x c e p t c r e a t i n i n e ) wer e d i r e c t l y r e l a t e d p r e s s i o n clue t o n e p h r i t i s , would a l s o c a l l f o r t h sup­ el though acute a r t h r i t i s an i n c r e a s e and a n e m i a m i g h t s o m e t i m e s i n d u c e chloride. t o t he r e n a l in blood u r i c e high le v e l acid of blood -9 4Case 7 59 4 ( Gr a de , Ms l e ) T h i s was p r o D s o l y a n o t h e r c a s e o f n a v e l i n f e c t i o n w i t h Staphylococcus sp. and a g r a m - n e g a t i v e r o d r e s u l t i n g i n t h e f o r m a t i o n of o v a r i e t y of l e s i o n s such as n e c r o s i s abscesses in h e a r t , s k i n and. s u o c u t a n e o u e t i s s u e , arthritis in the carpal H istory. T h i s l a me was br o u g h t i n A r e n t , on A / l i / 4 4 . ewe h a d d i e d . in liv er, and .joint. by Mr. W o c e i i e l d , County I t was t h e s m a l l e r o f a t w i n and t h e The lerno h a d an e n l a r g e d l e f t c a r p a l j o i n t and was Q u i t e l a m e . The a n i m a l became weaker' , g e t u p ana wa s k i l l e d a t 3 : 0 0 P . M. , could not 4 / ? 1 / 4 4 a t t h e age o f P0 d a y s . E t i o l ogy. A hem olytic S t aphylococcus carpal joint heart-clood and a. g r a m - n e g a t i v e r o d ( T a b l e 4: culture wrb isolated from l e f t ( Bact e r i u m s p . ) from 7394 a , p.) , B1 o,od.... s t u d i e s »., ( 9 ) -Blood p i c t u r e E r y t h r o c y t e s ................................................. 8 , 7 1 0 , 0 0 9 p e r c . mm. Leucocytes 14,600 11 H e m o g l o b i n ........................... IP g./lQ O cc. D i f f e r e n t i a l c o u n t (-/o) Ly.mphocyt e s . ...................... .13 N e u t r o p h i l s . ................................80 sc gme n t e r s ............................................... .. ( 73) b a n d s ................................................................. . . ( 7) M o n o c y t e s ........................................ ?, E o s i n o p h i l s ...................................... 0 B a s o p h i l s ........................................ 0 ( o ) Bl ood c h e m i s t r y ( Mgrn . / 111 cc .) G l u c o s e ............................................. 7 4 .4 4 Ur i c a c i d . .............................. 1.10 C r e a t i n i n e . ................................... 0.30 C h l o r i n e ........................................ 4 6 1 . 0 0 N. P . N . .............................................. 1 5 . 0 0 U r e a - N ................................................. 1 1 .20 ...... ............ ......... In co m p er i n g the r e s u l t s of bl o o d s t u d i e s e s se with th e normal s ta n d a rd ( Tables 1 & 2 ), o f e r y t h r o c y t e s was s omewhat l o w e r , higher, in th is t h e number h e m o g l o b i n s omewhat and l e u k o c y t e s d e c i d e d l y h i g h e r w i t h n e u t r o p h i l s ( 8 0 fo) p r e d o m i n a t i n g o v e r l y m p h o c y t e s ( 1 3 fo) , The s t r u c t u r e o f e r y t h r o c y t e s was r a t h e r n o r m a l , a l t h o u g h a few p o i k i l o c y t e s were o c c a s i o n a l l y o b s e r v e d . blood chem istry, t h e v a l u e s of N . P . N . r a t h e r low w h i l e t h e v a l u e s o f o t h e r fall within In r e s p e c t to and U r s a - K w e r e e l e m e n t s s e e me d t o thp normal r a n g e . Gross l e s i o n s . Suocuts.reous t i s s u e . in T h e r e was an a b s c e s s a b o u t 1 1 / 2 diameter in the subcutaneous t i s s u e s near the cm. thoraco­ abdominal w a l l . Joint . The l e f t carpal j o i n t was s w o l l e n and d i s t e n d e d and t h e j o i n t c a p s u l e was t h i c k e n e d and t h e c a v i t y f i l l e d w i t h c l o u d y . . f L o e c . u l e n t . . . e x u d a t e ...... A...siae air.ina.de from .the-.,.exudate ■.. showed a c t i v e H eart. phagocytosis. (Fig. 33) . Numer ous a b s c e s s e s w e r e p r e s e n t i n t h e h e a r t . was a m a r k e d p e r i c a r d i t i s being t i g h t l y Other o r g a n s . and m y o c a r d i t i s , adhered to t h e myocardium. Th e r e the percardium (Fig. 34) Apparently normal. Microscopic l e s i o n s . Liver. The l i v e r s howed e v i d e n c e s o f c o n g e s t i o n , swelling, some d i f f u s e degeneration, fatty and n e c r o t i c degeneration, cloudy some h y d r o p i c f o c i w i t h marked p o ly m e r p h o n u c le e Icucocytic i n f i l t r a t i o n . In g e n e r a l, the various lesions o f l i v e r i n t n i s c a s e r e s e m b l e d Q u i t e c l o s e l y t h o s e f ound i n Case # 7337 w i t h t h e e x c e p t i o n o f d i f f u s e f a t t y h y d r o p i c d e g e n e r a t i o n s w h i c h wer e n o t H eart. and found i n t h a t c as e. T h e r e wer e n u m e r o u s a b s c e s s e s i n t h e h e a r t and t h e y wer e f o u n d m o s t l y i n .myocardium and a few i n t h e epicardium. Due t o t h e f a c t t h a t some of t h e e p i c a r d i a l a o s e e s s e e r u p t u r e d and t h e i n f lam.natox’y e x u d a t e we n t i n t o the p e r i c a r d i a l rt 1 tS lilij | ip s ac, the pericardium CrJ^t' 0-1 u \J pUI* ci b i Vt; infiltration phages) The a b s c e s s e s w e r e shape, v a r i a ole in s i z e t o 5 mm. X 4 mm. ) , As £ P 'i C &X ‘0 1 "t 1 S HIy O U rU ‘U j. I i S , and p e r i c a r d i t i s a c t u a l l y e x i s t e d . irregular in De c a n e i n v o l v e d . ( 3 . 1 5 mm. X 0 . 1 2 mm. and w e r e c h a r a c t e r i z e d by m a r k e d c e l l ( oo t h p o l y m o r p h o n u c l e a r l e u c o c y t e s and ma c r o ­ s u r r o u n d e d oy an e x t e n s i v e The e n d o c a r d i u m , " J o i n t " c a p s u l e '. fiorosis (big. 55). h o w e v e r , was n o t a f f e c t e d . The “" j o i n t "'"capsule "of " " l e f t c a r pus showed a t y p i c a l l e s i o n o f an a c u t e suppurative arthritis somewhat l i k e t h a t f o u n d i n Case # 7 3 9 3 . Skin a b s c e s s . The s k i n l e s i o n was p a r t i a l l y o p e n e d out possessed a l l th e g e n e ra l c h a r a c t e r i s t i c s of a t y p i c a l aoscess. Except at the p o i n t wher e i t s t h e a o s c e s s wa s r ou n d e d on i t s outer l a y e r of e p i d e r m i s t o g e t h e r v i t a a c o r i u m ano on i t s i n n e r surface o p e n i n g was l o c a t e d , surface by a t h i n s m a ll p o r ti o n of ou ter by a t h i c k l a y e r o f f i b r o - u l a s t i c t i s s u e , w h i c h e x t e n d e d down t h e m u s c l e t i s s u e _P7_ underneath. On t n i s a c c o u n t , mo s t p a r t s o f t h e i n n e r c o r i u m a n d s t r a t u m su' bcut sneurn h a d b e e n d e s t r o y e d and replaced by f i b r o s i s . Other t i s s u e s . Those t i s s u e s etc., studied, wer e a l s o such as i n t e s t i n e s , but they kidneys, snowed no a b n o r m a l i t i e s . Summar y and d i s c u s s i o n . 1. T h i s l ame was s m a l l and weak due t o t h e p r e s e n c e of necrosis skin, 2. end h e m o r r h a g e s i n l i v e r , subcutaneous t i s s u e s , Bot h b a c t e r i a l i n f e c t i o n a b s cess es in h e a r t , end a r t h r i t i s i n c a r p a l .-joint. and a . D s e e s s - f o r m a t i o n r e s u l t e d i n a marked n e u t r o p h i l i e . 3. S i n c e t h e l i v e r was d a ma g e d , i t perform i t s apparently could not f u n c t i o n s p r o p e r l y in .main ta ining t h e normal l e v e l o f o l o o d u r e a and n o n - p r o t e i n n i t r o g e n . v a 1 u e s we r e r a t h e r l o w. These - 9 8C as e No. 7 5 6 ? ( S h r o p s h i r e , male) T h i s v;as a c a s e o f d o c k i n g i n f e c t i o n wh i c h r e s u l t e d i n a b s c e s s - f o r m a t i on o f t h e s p i n a l c o r d , c o n d i t i o n s w e r e an e n t e r i t i s , mild a s s o c ia te d and some d i s t u r b a n c e s in the l i v e r and k i d n e y s . Hi s t o r y . T h i s l a m b s h o we d b i l a t e r a l p a r a l y s i s o f t h e r e a r l i m b s on 3 / 5 1 / 4 4 and was b r o u g h t i t s mother. to the p a t h o l o g y barn w ith The l amb was k e p t u n d e r o b s e r v a t i o n e n t i r e ween and s howed no i m p r o v e m e n t . however, f o r an The a n i m a l , remained very b rig h t, nursed r e g u la rly , and i t s eemed d o u b t f u l w h e t h e r t h i s was " s t i f f - l a m b d i s e a s e " . On 4 / 7 / 4 4 , at t h e age o f 9 d a y s , t h e l a mb was b l e d a n d killed. Efiology, One s p e c i e s o f u n d e t e r m i n e d g r a . m - n e g a t i v e c o c c o i d b a c i l l u s was i s o l a t e d f r o m t h e l i v e r and two s p e c i e s o f Co r y -n e o r c t e r i u m wer e i s o l a t e d f r o m t h e spinal c o r d . u 1 t u r e ' No . 7 3 8 * , a blood Studies. ( a ) Bl o o d p i c t u r e E rythrocytes.. Leucocytes Hemoglobin. . . . D i f f e r e n t i a l count Lymp ho c y t e s , N eutrophils. s e g me n t e r s oands juveniles monocytes.. Eosinophils Basophils. . 8 , 6 7 0 , 0 1 1 p e r c.mm. Q CggO n ii 9 . 8 g./lO O cc. {'jo) 35 (56) ( 6) ( 3) 0 0 0 -99- ( b ) Blood, c h e m i s t r y ( Mgm/ 1 0 0 cc .) G l u c o s e ................................................... 9 7 . 5 0 U r i c a c i d ............................................. l.iO C r e a t i n i n e ........................................... 1 .0 0 C h l o r i d e ................................................. 430 . 0 0 N . P . N ........................................................ 3 4 . 0 0 U r e a - N ..................................................... 1 1 . 9 0 Ex c e p t f o r some l e u c o c y t o s i s w i t h i n c r e a s e d n e u t r o p h i l s , reduced lymphocytes, and s l i g h t i n c r e a s e in glucose, v a r i o u s v a l u e s o f t h e c! >oo e l e m e n t s o f t n i s mnnn n i_ *f r onf -fih tsn +. r, r\ R o o f ’ r.o frn .n l 1.3 Tib S . the l a mb w e r e n o t T 'l C rIi OV p i H1 0 C' y o f e r y t h r o c y t e s was n o r m a l . Gross l e s i o n s . Sk e l e t a l m u s c l e s . T h e r e was some a t r o p h y o f t h e m u s c l e s o f the re a r lim es. Tail-he ad. site, In the re g io n of the ta iln e a d at a g r e e n i s h c o l o r e d p u s was p r e s e n t . t h e cl ocki ng This s u p p u ra tiv e .J. e-si on e x t e n d e r s int-c a n d - i n v o l v e d - t h e . s p i n a l "Cor d -as f a r --ast h e c e n t e r o f t h e lumbar' a r e a . Ot h e r o r g a n s . (Fig. 36) Aop a r e n t ] , y h o r :na 1. hi cr oscopic 1 e s i o n s . Liver.* The l i v e r s aowec c o n g e s t i o n , diffuse fatty degeneration, cloudy s w e l li n g , and o c c a s i o n a l t i n y n e c r o t i c f o c i w i t h a p o l y m o r p h o n u c l e a r l eucoc- y t i c The l e s i o n s we r e s o mown at- s i m i l a r t o Li v er o f Case # 7 3 5 6 . infiltration. t h o s e fou nd in t hp -100Intestine . The i n t e s t i n e involving: p a r t i c u l a r l y s howed l e s i o n s the mid-gut. Th e r e was a s u p e r f i c i a l n e c r o s i s i n v o l v i n g Doth t h e e p i t h e l i u m w i t h a m o d e r a t e ma c r o p h a g e r e a c t i o n Kidneys. of a m i l d e n t e r i t i s , and l a m i n a p r o p r i a in the subnecrotic zone. The k i d n e y s w e r e s u s p e c t e d o f h a v i n g a c o n g e n i t a l cystic condition. t u o u l e s were excretion Her e and t h e r e , t h e p r o x i m a l c o n v o l u t e d dilated to the c y s t i c sta g e with u r i n a r y and s o m e t i m e s c o n t a i n e d a l b u m i n o u s c a s t s . i i oroi' 1 a s t i c p r o l i f e r a t i o n was a l s o o b s e r v e d i n t h p s e affected a re a s . whs b e l i e v e d Some As t h e a n i m a l was y o u n g , th is condition to have d e v e l o p e d i n i n t r a - u t e r i n e life. The e p i t h e l i u m o f t h e c o n v o l u t e d t u b u l e s showed c l o u d y s w e l l i n g , and o c c a s i o n a l l y small, f o c i o f l y m p h o c y t i c i n f i l t r a t i o n we r e n o t e d . Br a i n . B r a i n was s l i g h t l y congested, otherwise i t seemed The s p i n a ] , c o r d was s e v e r e l y i n j u r e d by t h e normal. Spinal c o r d . cl ocki ng i n f e c t i o n wh i c h r e s u l t e d i n fi orosis. The t i s s u e r e a c t i o n ab s c e s s - f o r m a t i on and s eemed t o s t a r t s u b s t a n c e o f t h e cord, a l o n g t h e c e n t r a l lesion gradually c a n a l and t h e spread t o the s u rr o u n d in g are a s . t h e l i a l l i n i n g o f t h e c e n t r a l c a n a l was f i r s t a s t h e s e c e l l s we r e i n v o l v e d , infiltration i n th e grey took, p l a c e . the surrounding tissu e s The e p i ­ attacked, and s. p o l y m o r p h o n u o l e e r l e u c o c y t i c As t h e p r o c e s s d e v e l o p e d , more o f oecs.me i n v o l v e d and more p o l y ­ morphonuclear le u c o c y te s m igrated to the a r e a . I n some -101sections of the a f f e c t e d c o r d , morphonuclear le u c o c y tic Doth p e r i v a s c u l a r p o l y ­ infiltration along the commissures were r e a d i l y affected tissu e s waa f o r m e d . observed. ’b ecame n e c r o t i c and p a r t l y oy t h e p o l y m o r p h o n u c l e a r s o l v e d by t h e i r and i n f i l t r a t i o n When t h e s e phagoeytized leucocytes or p a r t i a l l y proteolytic In g e n e r a l , enzyme, a recently end t h e f o l J o wi n g c h a r a c t e r i e t i c s : dis­ a sem i-liq u id abscess formed a o s c e s s (Fig. 37 a liqui fie d center V-:ith some s e m i - s o l . i d e x u d a t e , & z c n e o f d a r k - s t a i n e d m a t e r i a l c o n s i s t i n g m o stly of dying polymorphonuclear . l e u c o c y t e s e nd some f i b r i n , tissue i n f i l t r a t e d with and a z o n e o f a f f e c t e d n e r v o u s active The a f f e c t e d nerve, c e l l s oolymorphonuclesr leucocytes end n e u r o g l i a t o o k e o s i n s t a i n and t h e n u c l e i h a d e i t h e r d i s a p p e a re d o r undergone pyknosis I n t h e mor e a d v a n c e d o r o l o e r r- esc e s s h a d slightly lesion, the d ifferent m anifestations. spinal Besides a l l t h e c h a r a c t e r ! s t i e s .. ment i oned, p r e v i o u s l y , f o r t h e ..recently,... • formed a b s c e s s , two o t h e r e l e m e n t s were o b s e r v e d , namely, a narked i n f i l t r a t i o n o f m a c r o p h a g e s i n t h e 3 r d l a y e r and e pronounced f i b r o s i s in the 4th l a y e r - . t h e r e were f i v e d i f f e r e n t As a r e s u l t , zones i n t h e o l d e r a b s c e s s i n s t e a o f t h r e e z o n e s a s wer e f o u n d i n t h e more r e c e n t o n e . endothelium of c a p i l l a r i e s l o c a t e d on t h e w a l l s o f t h e o l d e r a b s c e s s e s was p r o l i f e r o t i n g hyperplasia, The and showed e v i d e n c e o f s u g g e s t i n g : t h a t t h e i r a c t i v i t y was s t i l l -10?- proceeding. The e t i o l o g i c a l a g e n t , the d ip h th e ro id s , was o b s e r v e d i n t h e i n n e r second l a y e r of t h e a b s c e s s e s . Other t i s s u e s. Ot h e r t i s s u e s wer e mor e o r l e s s n o r m a l . Summary and d i s c u s s i o n : } 1 . T h i s was s c a s e o f d o c k i n g i n f e c t i o n r e s u l t i n g in a b s c e s s —f o r m a t i o n o f t h e s p i n a l c o r d , m i l d e n t e r i t i s , and some d i s t u r b a n c e s ?. in the l i v e r The a n i m a l showed b i l a t e r i a . 1 and k i d n e y s . p a r a l y s i s in th e r e a r limbs due t o i n v o l v e m e n t o f t h e l u m b o - s a c r a l r e g i o n s p i n a l c o r d by e o s c e s s - f c r m a t i o n and n a t u r a l l y n e r v e s s u p p ly i n g t h e r e a r limbs had ceased t o 3. A b a c t e r i a l i n f e c t i o n of the the function. of the t a i l - h e a d caused the mild neutrophilia. 4. B l o o d g l u c o s e was s l i g h t l y increased. t h a t was p r o b a b l y t h e r e s u l t 5. The lamb r e m a i n e d b r i g h t th a t the mild e n t e r i t i s The r e a s o n f o r of impaired, l i v e r throughout l i f e , function. which i n d i c a t e d and d i s t u r b a n c e s i n the l i v e r and k i d n e y s wer e r e c e n t d e v e l o p m e n t s a n d g e n e r a l s y s t e m i c i n v o l v e m e n t was n o t a p p a r e n t . -103- Case 7365 ( H a m p s h i r e , m a l e ) Th i s was a c a s e o f d o c k i n g i n f e c t i o n r e s e m b l e d Case # 7 3 6 ? . serious, since it and somewhat Ho we v e r , t h i s c a s e was more s c u t e and had a c o m b i n e d i n f e c t i o n o f A c t i n o m y c e s n e c r o p h o r u s and C o r y n e b s c t e r i u m s p . , r e s u l t i n g i n t h e f o r m a ­ tion of a c s c e s s e s a r o u n d t h e c e n t r a l c a n a l o f t h e c o r d , hemorrhages in the spinal a r a c h n o i d membrane o f t h e m e n i n g e s , a nd an a c u t e v a l v u l a r e n d o c a r d i t i s . Hi s t o r y . T h i s lamb was n o t i c e d t o h a v e some p a r a l y s i s o f t h e r e a r l i m b s on t h e m o r n i n g of' 4 / 8 / 4 4 . held up to the mother. I t n u r s e d w e l l when The lamb was f o u n d d e a d a t 8 : 0 0 A.M. t wo d a y s l a t e r when i t was a b o u t one month o l d . E t i ol o g y . C o r y n e b a c t e r i u m s p . and A c t i n o m y c e s n e c r o p h o r us were i s o l a t e d from th e s p i n a l c o r d . A c t i n o myces n e c r o p h o r u s was c u l t u r e d i n d e e p b r a i n b r o t h , w h i l e t h e g e n e r a l characteristics i n T a b l e 4: o f t h e C o r y n e b s c t e r i u m sp. C u l t u r e No. are r e f e r r e d to 7365. Gross l e s i o n s . U rinary b l a d d e r . The b l a d d e r was d i s t e n d e d t o t h e e x t e n t t h a t u r i n e was p r e s e n t i n t h e p e l v i s o f t h e k i d n e y s p r o ­ ducing a h y d r o n e p h ro s is. Tailhead. vicinity t h e u r e t h r a was o pe n. The d o c k i n g wound was n o t h e a l e d . considerable splitting However, inflammation present about th is t h e v e r t e b r a l co l u mn , T h e r e was area. Upon e x u d a t e was f o u n d i n t h e o f t h e c a u d a e q u i n e and t h e i n f l a m m a t o r y p r o c e s s -134e x t e n d e d up t h e c e n t r a l c a n a l t o a p o i n t posterior p art of the lumbar r e g i o n . l o c a t e d a t the In the lumbar r e g i o n , t h e r e was an e x t e n s i v e h e m o r r h a g e a r o u n d t h e s p i n a l c o r d a p p r o x i m a t e l y P . 5 cm. i n B ic u sp id v a l v e . length. The b i c u s p i d , v a l v e s howed some a r e a s o f i n f l a mma t i o n . Other organs. No v i s i b l e l e s i o n s were o b s e rv e d , icroscopic le s io n s . S p i r a l cor d . He mo r r h a g e was r a t h e r a r a c h n o i d memb r a n e. the subdural I t was o b s e r v e d t h a t space f o r a c o n s i d e r a b l e wh o l e d o r s a l h a l f o f t h e around the a nd i t extensive t he b l o o d f l o o d e d area, spinal cord. c o v e r i n g the The a b s c e s s c e n t r a l p o r t i o n o f t h e c o r d was r e c e n t l y resembled ra th e r closely that Besides t h i s aoscess, abscess-like spots located one of t h e s e considerably In t h e s e dilated. 38) f o r med t h e r e wer e f o u r g r e a t l y i n f l a m e d o r in the p e riv a sc u la r1 a r e a s , f o u r a r e a s wa s a l r e a d y small abscess. (Fig. f o u n d i n Ca s e #7 36?. on pach of, t h e ..mix;e d,,la,t e r . a l , t r a c t . s of,. C a j a l , loosened, in the lesions, two In: f-act-y ■. transformed in to a the c a p i l l a r i e s were The e n d o t h e l i u m was s w o l l e n , and p o l y m o r p h o n u c l e a r l e u c o c y t e s h a d m i g r a t e d through the c a p i l l a r y w a l l s . The e n d o t h e l i a l l a y e r was s u r r o u n d e d by a c l e a r 1 z o n e f i l l e d w i t h e d e m a t o u s f l u i d and cells and l i m i t e d by a d e l i c a t e l a y e r of f i b r o u s t i s s u e wh i c h was i n t u r n s u r r b u n d e d by a c l e a r space of about th e same s i z e a s t h e p r e v i o u s m e n t i o n e d a r e a . Finally, l a y e r o f f i b r i n was n o t i c e d a t t h e o u t e r m o s t l i m i t a dense of th e - 1 0 5lesion. The e t i o l o g i c a l agents, Ac t i n o my c e s n e c r o p h o r u s , the c e n t r a l a b sc e ss, w e r e o b s e r v e d i n t h e e x u d a t e of and i t indicated clearly th a t c a s e was one o f mi x e d i n f e c t i o n Bicuspid v a l v e . C o r yne b a c t e r i u m s p . and (Fig. The l e s i o n i n t h e this 39). b i c u s p i d v a l v e of the h e a r t c o n s i s t e d of h e m o r r h a g e , n e c r o s i s , and e mar k ed p o l y m o r p h o n u c l e a r l e u c o c y t i c i n f i l t r a t i o n m i x e d w i t h some fibrin. A short distance fibroblastic d e f in ite wall Actually, c e l l s wer e f r om t h e actively affected area, proliferating, the although a s e g r e g a t i n g t h e i n f l a m e d are had n o t formed. the le s io n in the bicuspid valve c o n s t i t u t e d wh a t i s known a s a c u t e v a l v u l a r e n d o - c s r d i t i s . -106- Case 7370 ( G r a d e , m a le ) T n i s l a mb s u f f e r e d f r o m i n f e c t i o n Hist o r y . T h i s a n i m a l was c a s t r a t e d a b o u t d e a t h whi c h o c c u r r e d on 4/ 10/ 4- 4. be s t i f f o f t h e c a s t r a t i o n wound. The l amb was n o t i c e d t o i n t h e l e f t h i n d l e g on t h e t a l k i n g w i t h t h e own er , been a esse of Gross pathology. in heeling, it t h r e e weeks b e f o r e was f e l t previous day. Upon t h a t t h i s m ig ht have "stiff-lam b disease". The s c r o t u m had b e e n p a r t i a l l y t h e wool and s k i n had t u r n e d i n . removed, and The wniiriri h a d f a i l e d t o h e a l and t h e i n f l a m m a t o r y p r o c e s s e x t e n d e d from the s c r o t a l r e g i o n a l o n g the l e f t abdominal w a l l f a r f o r w a r d a s t h e e nd o f t h e p e n i a l visible sheath. and a s No o t h e r l e s i o n s were o b s e r v e d and a p p a r e n t l y t h i s was n o t a case of w h i t e-muscle d i s e a s e , wer e o b s e r v e d . s i n c e no m u s c u l a r l e s i o n s -107Case 7P8? ( H a m p s h i r e , mele) T h i s was a c a s e o f b r o n c h o p n e u m o n i a . Hi s t o r y . T h i s a n i m a l was b o r n on 2 / P 8 / 4 4 . t o be d r o o p y , as though i t ceased to suckle, ha d pneumonia. I t was n o t i c e d and o r e a t h e d . w i t h d i f f i c u l t y I t was t h e n t r e a t e d w i t h pn e u mon i a s e r u m and m i n e r a l o i l . The lamb d i e d when i t was t h r e e d a y s o f a g e . Gross pathology Lungs. F r o t h y muccue e x u d a t e war. p r e s e n t i n t h e t r a c h e a and b r o n c h i . Some c o n g e s t i o n o f t h e mucous membrane of t h e l o w e r t r a c h e a and b r o n c h i was n o t i c e d . Moreover, an a c u t e f u l m i n a t i n g and r a p i d l y - s p r e a d i n g b r o n c h o p n e u m o n i a was f o u n d i n t h e a p i c a l , cardiac and a n t e r i o r o n e - f o u r t h o f the d ia p h r a g m a t ic l o b e s of both l u n g s . Liver. T h e r e we r e s m a l l w h i t e f o c i t hroughout "" t h e ■'liver-." increased in Other o r g a n s . - T h e - l i v e r - was ""friable- "and - s l i g h t l y - - — size. Apparently normal. Bacterial cu ltu re. a b o u t 1 mm. i n d i a m e t e r N egative. -108Ca.se 730 8 ( S o u t h d o w n , mal e) T h i s was a c a s e o f p a s s i v e h y p e r e mi a , r e s u l t i n g from an open ductus a r t e r i o s u s His t o r y . and c o m p l i c a t e d w i t h b r o n c h o p n e u m o n i a . . T h i s l amb was b o r n on P / 8 9 / 4 4 . On 3 / 5 / 4 4 , the l amb was n o t i c e d b r e a t h i n g h e a v i l y a nd was g i v e n 20 c c . o f pneumonia, serum s u b c u t a n e o u s l y . same dos e o f s er um was a g a i n g i v e n . t h e l amb a p p e a r e 6 b r i g h t e r Two d a y s l a t e r , the A fter each i n j e c t i o n , and more a c t i v e . Ho we ve r , i t was found, d e e d on 3 / 9 / 4 4 . Etiology. A gram-negative rod ( Eae Leri um s p . ) was i s o l a t e d See Ta b l e 4: from the l u n g s . c u l t u r e No. 7308 f o r i t s g en er a 1 c h a r a c t e r i s t i c s . Gross l e s i o n s . Lungs. The r e was a m a r k e d c o n g e s t i o n o f t h e l u n g s w i t h some r e c e n t p n e u mo n i a on t h e r i g h t apical, cardiac s id e in v o lv in g the and s m a l l p o r t i o n o f t h e d i a p h r a g m a t i c lobes. .... ...................................... .... Liver. The l i v e r was v e r y much c o n g e s t e d . e n l a r g e d by a t l e a s t Heart. .■--■■■■■. ..... T h i s o r g a n was one-third. The d u c t u s a r t e r i o s u s was o pen whi ch a l l o w e d t h e f r e e p a s s a g e of blood i n t o t h e a o r t a from t h e pulmonary artery. O t h e r or g a n s . A p p ar en tly normal. Microscopic l e s i o n s . Li v e r . The l i v e r diffuse fa tty showed a c u t e v e n o u s c o n g e s t i o n w i t h m a r k e d d e g e n e r a t i o n and n e c r o s i s . F a t g l o b u l e s wer e p r e s e n t n ot only i n c e l l s l o c a t e d at the p e r i p h e r y of t h e h e p a t i c lo b u le b u t a l s o in the i n t e r m e d i a t e the lobule. Alm ost every c e l l and c e n t r a l p a r t s of i n t h e l o b u l e was i n v o l v e d Some c e l l s c o n t a i n e d a n u mb e r o f v a r i o u s s i z e d f a t i n whi ch c a s e t h e n u c l e u s was s t i l l globul centrally located, w h i l e o t h e r s c o n t a i n e d j u s t one l a r g e f a t g l o b u l e and t h e n u c l e u s was p u s h e d t o one s i d e o f t h e c e l l and f l a t t e n e d so t h a t t h e c e l l r e s e m o l e d t h o s e o f a d i p o s e t i s s u e . some l o b u l e s , In t h e n e c r o s i s h a d e x t e n d e d a l m o s t a r o u n d t he central vein. (Fig. 40) The h y p e r e m i a was g e n e r a l i z e d , b u t i n some s p o t s i t was s o e x t e n s i v e t h a t t h e s i n u s o i d s h a d r u p t u r e d and c o n s e q u e n t l y h e m o r r h a g e o c c u r r e d . Intestine. Due t o a c u t e p a s s i v e h y p e r e m i a , was a l s o a f f e c t e d . much c o n g e s t e d , The i n t e s t i n a l the i n t e s t i n e c a p i l l a r i e s were very and t h e r e was some m u c o i d d e g e n e r a t i o n of the e p ith e liu m . Lungs. The l u n g s wer e c o n g e s t e d a n d s howed l e s i o n s o f a t y p i c a l b r o n c h o p n e u m o n i a o f r e c e n t d e v e l o p m e n t T h e “p o l y m o r p h o n u c l e a r c e l l i n f i l t r a t i o n was t h e p r e d o m i n a t i n g f e a t u r e t h r o u g h o u t t h e p n e u mo ni c a r e a s . Other t i s s u e s . Ot h e r t i s s u e s wer e mor e o r l e s s n o r m a l . -110Case 7509 ( B l a c k Top D e l a i n e , f e m a l e ) Th i s was a c a s e of i n t e r s t i t i a l br o n c h o p n e u mo n i a w i t h marked p a s s i v e c o n g e s t i o n of l i v e r and k i d n e y s . H istory. T h i s l a mb was 7 : 3 0 A.M. o f t h e Etiology. same b o r n on 5 / 2 1 / 4 4 and was found dead a t day. No b a c t e r i a w e r e i s o l a t e d f r o m t h i s c a s e . Cross l e s i o n s . Lungs. No e v i d e n c e t h a t Liver. S lig h tly mottled. Other o r g a n s . t h e larnD h a d e v e r b r e a t h e d . Apparently normal. Microscopic l e s i o n s . Lungs. The l e s i o n s i n t h e l u n g s were i n t e r e s t i n g . a c a s e of i n t e r s t i t i a l during f e t a l life. I t was br onchopne umoni a h a v i n g d e v e l o p e d In a d d i t i o n t o a l l those g e n e r a l c h a r a c t e r i s t i c s found i n a. t y p i c a l b r o n c h o p n e u m o n i a , t h e r e was a marked l y m p h o c y t i c i n f i l t r a t i o n . These l ymphoi d c e l l s were found m o s t l y i n t h e a l v e o l a r w a l l s , b u t some o f them f e r e a l s o f ound i n t h e p e r i b r o n c h i a l and p e r i ­ vascular regions. Here and t h e r e , g r o u p s of t h e s e c e l l s we r e i n a g g r e g a t e f o r m i n g t u b e r c l e - l i k e s t r u c t u r e s . (Fig. 41, 42) the alveoli The a l v e o l a r w a l l s we r e t h i c k e n e d w h i l e we r e e i t h e r i n f i l t r a t e d w i t h m a c r o p h a g e s and a few p o l y m o r p h o n u c l e a r l e u c o c y t e s o r d i s t e n d e d w i t h edematous f l u i d . exudate, The b r o n c h i o l e s c o n t a i n e d , i n f l a m m a t o r y c o n s i s t i n g o f some mucous m a t e r i a l m i x e d w i t h -Illpolymorphonuclear le u c o c y te s . affected lungs, proliferation In c e r t a i n a r e a s of the t h e r e wa s e v i d e n c e o f f i b r o b l a s t i c in the a l v e o l a r w a l l s as w e l l as i n the p e r i b r o n c h i a l a nd p e r i v a s c u l a r r e g i o n , w h i l e i n o t h e r s — e s p e c i a l l y in those near the b r o n c h ia l w alls q u i t e a number o f p l a s m a c e l l s w e r e o b s e r v e d . Occasionally, g i a n t c e l l s were found i n c e r t a i n a l v e o l i . In g e n e r a l , t h e a l v e o l i w e r e more o r l e s s i n an a c t e l e c t a t i c condition, o u t t n i s c o n d i t i o n was i n t e r r u p t e d h e r e and t h e r e by a r e a s o f c o m p e n s a t o r y emphysema wh i c h i n d i c a t e d t h a t t h e l amb h a d b r e a t h e d f o r some t i m e a f t e r Liver . The l i v e r was e x c e e d i n g l y narked f a t t y degeneration. birth. c o n g e s t e d and showed The s i n u s o i d s w e r e g r e a t l y e n l a r g e d end f i l l e d w i t h an e x c e s s i v e number o f b l o o d cells. The f a t t y d e g e n e r a t i o n was p r o n o u n c e d a n d d i f f u s e , in v o lv in g p r a c t i c a l l y every h e p a tic c e l l in the l i v e r . Most, h e p a t i c c e l l s . n p n t a l n e . d , j ? n e . to ...several. l a r g e fa.t g l o b u l e s so t h a t ...... the n u c l e i e i t h e r were pushed t o th e s i d e of t h e c e l l or wer e d e p r i v e d o f n u t r i t i o n a n d showed karyolysis. Kidneys. The k i d n e y s s nowed mar ked c o n g e s t i o n and. hemorrhage, tissues. i n v o l v i n g b o t h p a r e n c h y m a and. i n t e r s t i t i a l T h r o u g h o u t t h e c o r t e x and m e d u l l a , an e x c e s s i v e number o f e r y t h r o c y t e s w e r e o b s e r v e d w i t h i n t h e i n t e r ­ l o b u l a r c a p i l l a r i e s and c a p i l l a r i e s in the m e d u l l a r y a r e a . The g l o m e r u l i we r e a l s o r a t h e r c o n g e s t e d and a c a s e of glom erular hemorrhage a c t u a l l y e x i s t e d so t h a t blood c e l l s l l« '“ w e r e f o u n d i n s i d e Q u i t e a number o f t h e c o n v o l u t e d t u b u l e s as w e l l as i n t h e Other o r g a n s . normal. collecting; tubules. O t h e r o r g a n s wer e n o t a f f e c t e d a n d seemed -1 1 3 C s s e 7550 (Shropshire, female) T h i s was a c a s e o f b r o n c h o p n e u m o n i a w i t h p r o b a b l y some o t h e r Hi s t o r y . com plication. The l a m b was o wn e d by A. E. Michigan. I t was a l a r g e weeks of a g e . (3/2.5/44) H oltforth, w e l l - n o u r i s h e d l a mb a b o u t a n d t h e c a r c a s s was b e g i n n i n g t o d e c o m p o s e and was X. A gram-negative rod 4 -V. ^ A KJAl three The a n i m a l d i e d s u d d e n l y t h e p r e v i o u s e v e n i n g b a d l y b l o a t e d when D r o u g h t t o t h e l a b o r a t o r y Etiology. Fenton, f 1 ni-v- uxic- ~ i c i o j . 0 for autopsy. ( B a c t e r i um s p . ) was i s o l a t e d A • ^ ,,,1 d -,, nr « b U l U U I yr_ c O rj INU* < \ *-A> / Gross p a t h o l o g y . Stomach. On t h e l e s s e r c u r v a t u r e o f t h e s t o m a c h , was a l a r g e m e mb r a n e . a r e a o f h e m o r r h a g e and e r o s i o n Surrounding t h i s area, were t h i c k e n e d Lungs. sufficient to cm. o f t h e mucous t h e f o l d s of t h e stomach and w e r e v e r y h a r d . P n e u m o n i a was p r e s e n t i n t h e r i g h t a p i c a l and card!ab' T a b e s He a r t . to about 1 . 0 there The" p n e u m o n i a ; did" n o t - a p p e a r ;' t o"be""of" e x te n t to cause death. T h e r e wa s a n e x t e n s i o n o f t h e inflammatory process t h e p e r i c a r d i u m w i t h some h e m o r r h a g e on t h e p e r i c a r d i u m and e x c e s s o f p e r i c a r d i a l Oth e r o r g a n s . fluid. Apparen11 y n o rm a l. .. -1 1 4 Ca s e 7551 T h i s wa s a n o t h e r c a s e ( Shr ops h i r e m a l e ) of bronchopneumonia w ith p r o b a b l y some o t h e r c o m p l i c a t i o n . Hi s t o r y . The l a m b was s m a l l and weak and h a d n o t The a n i m a l came f r om t h e same f a r m a s w ell since b i r t h . Cas e # 7 3 5 0 . It been doing d i e d on 3 / 2 5 / 4 4 when i t was a b o u t one week o l d . E t i o l ogy. A gram -negative rod from the l u n g s , and i t s t i on e d i n 4 Table Gross patho l ogy. : ( B acterium s p . ) was i s o l a t e d general c h a r a c te r is tic s c u l t u r e ho. 7551. There w a s a v e r y s l i g h t pneumonia i n t h e r i g h t apical lobe. o t h e r l e s i o n s were o b s e r v e d . a r e men- amount o f p a t c h y Besides t h i s , no -1 1 5 ^ aSe 7353 ( S o u t h d o w n , female) T h i s l a mb s u f f e r e d f r o m an a c u t e h e m o r r h a g i c b r o n c h o ­ pneumonia. Hi s t o r y . This animal had not been a b l e t o s t a n d on i t s f r o n t l e g s and d i e d i n t h e morning of wa s a b o u t Etiology. two d a y s o l d . A gram-negative rod from l i v e r , tics No. h e a rt blood, this rvf 4 / 1 / 4 4 when i t ( B a c t e r i u m s p . ) was i s o l a t e d and l u n g s . micro-organism The g e n e r a l c h a r a c t e r i s ­ are given in l a b l e 4: culture 7353 . Gross l e s i o n s . Trachea. Lungs. Contained frothy foam. Showed r e d d e n e d a r e a s w h i c h w e r e s o l i d i f i e d , s u g g e s t i n g e i t h e r h e m o r r h a g e or b e g i n n i n g b r o n c h o p n e u m o n i a . M e s e n t e r i c lymph n o d e s . ■■■"■ O ther - - o r g a n s C o n g e s t e d and somewhat e n l a r g e d . No" v i s i b l e . ' l e s i o n s . ■o b s e r v e d . Microscopic l e s i o n s . - ■■■• The l u n g s s h owe d a v e r y a c u t e h e m o r r h a g i c ty p e of bronchopneumonia. I t was t h e mos t s e v e r e c a s e o f bronchopneumonia observed during the e n t i r e lambing season la s t year. The l u n g s w e r e e x c e e d i n g l y hemorrhagic. feature of t h e In f a c t , lesion, and. a l m o s t e v e r y w h e r e i n t h e l u n g an b r o n c h i o l e s were v er y b a d l y i n f l a m e d surrounding a lv e o li matory c e l l s , solidated fiorin, c o n g e s t e d and h e m o r r h a g e wa s t h e mo s t p r e d o m i n a t i n g e x c e s s i v e number of e r y t h r o c y t e s were as the .. observed. The and t h e lurnina. a s w e l l wer e f i l l e d w i t h e i t h e r or e r y t h r o c y t e s . (Fig. 43) inflam­ The c o n ­ a r e a s we r e i n t e r r u p t e d by a r e a s o f c o n g e s t i o n , -1 1 6 collapse, and emphysema, a ty p ic a l case follow ing the of bronchopneumonia. v e r y much c o n g e s t e d a n d s w o l l e n . same p a t t e r n as The s e r o s a was a l s o -1 1 7 - C a s e s 7371 & 7373 ( S h r o p s h i r e f e m a l e & m a l e ) The s e t wo c a s e s s h o we d b r o n c h o p n e u m o n i a c o m p l i c a t e d w i t h Actinomyces n e c r o p h o r u s i n f e c t i o n of t h e Hi s t o r y . T h e s e two l a m b s came f r o m t h e Michigan. lungs. Ce s o r F a r m, New H u d s o n , One o f t hem was b o r n on P / 7 8 / 4 4 , w h i l e on 3 / 8 / 4 4 . Both were g i v e n out they died serum t r e a t m e n t f o r on t h e seme day ( 4 / 1 1 / 4 - 4 ) the o th e r pneumonia, in s p i t e of t h e t r e atrnent. Etiology. Two s p e c i e s o f b a c t e r i a w e r e l u n g s and p e r i c a r d i a l No. 7371 a , ( T a b l e 4: b) o f c a s e 73 71 ( T a b l e 4: and - t h r e e f r o m t h e l u n g s o f c a s e culture morphologically sac i s o l a t e d from the No. sim ilar 7373 a, o, c). culture 7 37 3 A micro-organism t o A c t i n o m y c e s n e c r o p h o r u s was i s o l a t e d from t h e l u n g s of each c a s e by deep b r a i n broth culture. Gross p a th o lo g y . Lungs. The l u n g s w e r e g r e e n i s h b r o w n i n c o l o r exudate in the l o w e r t r a c h e a , was a l s o and the g r e e n i s h b r o wn and had a p u t r i d smell. Numerous g r e e n i s h c o l o r e d a b s c e s s e s were p r e s e n t t h r o u g h o u t t h e l u n g s and t h e r e were a d h e s i o n s of the lu n g s to the r i b s . fibrinous p e ric a rd itis in I n c a s e 7 3 7 1 , t h e r e w a s a. addition to the lung l e s i o n s . -1 1 8 - Cas e 7401 (Shropshire, T h i s was s. c a s e o f a c u t e female) s u p p u r a t i v e bronchopneumonia. c o m p l i c a t e d by a m i l d e n t e r i t i s . H istory. 9 :0 0 T h i s l a m o was 24 d a y s o l d a n d was f o u n d d e a d a t A.M. 4/?4/44-. The larnb h a d b e e n n u r s i n g a g o a t and a p p e a r e d n o r m a l t h e day b e f o r e i t s Etiology. isolated death. Three d i f f e r e n t k i n d s of m i c r o - o r g a n i s m s were from t h i s lamb, ( Bacterium namely, one f r om h e a r t b l o o d s n . ) end two f r o m t h e l u n g s and N e i s s e r i a s p .). r e f e r r e d to i n Their general c h a r a c t e r i s t i c s T a b l e 4: c u l t u r e s No. G r o s s l e s i o n s . Upon r e m o v i n g t h e s k i n , t o be r a t h e r Intestine. ileum. (Pasteu r e l l a 7 401 a , d, sp. are c. t h e c a r c a s s was f o u n d e m a c i a t e d an d th e lamb had a s e v e r e T h e r e was a s l i g h t e n t e r i t i s present diarrhea. i n the No f o r m e d f e c e s w e r e f o u n d i n t h e r e c t u m . Lungs-. ■■..B r o n c h o p n e u m o n i a . . .w,&s,...present..., in..,_the . a p i c a l a n d c a r d i a c l o b e s of the r i g h t lung. involvement of the l e f t lung. T h e r e was o n l y Trie p n e u m o n i a w o u l d n o t oe c o n s i d e r e d s e v e r e e n o u g h t o be t h e M icroscopic l e s i o n s . study. in stages, o e e n damage d e s p e c i a l l y one i n s t a n c e , 5 entire cause of d eath . Onl y l u n g t i s s u e was p r e s e r v e d f o r B o t h t h e p n e u m o n i a and t h e beginning a c tiv e slight suppurative f o c i wer e and much l u n g t i s s u e s h a d by t h e s u p p u r a t i v e p r o c e s s e s . a relatively In l a r g e a r e a o f a b o u t 4 mm. by mm. was o c c u p i e d and d e s t r o y e d , by a. s p r e a d i n g a b s c e s s . C a s e 7410 ( H a m p s h i r e , m a l e ) T h i s was a c a s e o f a c u t e s u p p u r a t i v e bronchopneumonia complicated w ith e n t e r i t i s . Hi s t o r y . The l a mb s howed m i l d s c o u r i n g on 4 / 2 7 / 4 4 a n d was found dead t h e n e x t m o rn i n g . Etiology. I t was a b o u t 2 5 d a y s o l d . ^ g ram -negative rod from t h e l u n g . (Table 4: (B a c t e r i u m s p . ) was i s o l a t e d culture No. 7410) Gro s s l e s i o n s . Lungs. Bronchopneumonia was p r e s e n t on b o t h a p i c a l , c a r d i a . c a n d a n t e r i o r t h i r d ox t h e r i g h t lobes. The p n e u m o n i a wa s p r o g r e s s i v e m a r k e d zone o f c o n g e s t i o n b e t w e e n t h e u i a phi'-a g m « t i e a s t h e r e wa s s p n e u m o n i c a r e a and t h e normal lu n g . Intestine. T h e r e was s l i g h t c o n g e s t i o n o f t h e P e y e r ' s p a t c h e s and t h e mu c o s a o f t h e s m a l l i n t e s t i n e . No formed, f e c e s were fo u n d in t h e c o l o n or r e c t u m . Other organs'. 'Apparently" n o r m a l . Microscopic l e s i o n s . right In s tu d y in g the a n te rio r cardiac of the lu n g s , s e c t i o n s t a k e n from l o b e and r i g h t a case of t y p i c a l ac u te pneumoni a. w a s n o t e d . diaphragm atic lobe s u p p u r a t iv e broncho­ The b r o n c h i o l e s w e r e s e v e r e l y damaged and t h e i r l u m i n a were f i l l e d w i t h i n f l a m m a t o r y e x u d a t e c o n s i s t i n g m o stly of polym orphonuclear le u c o c y t e s desquamated e p i t h e l i a l c e l l s . The a l v e o l i and. s u r r o u n d in g each inflam ed b ro n c h io le c o n ta in e d m ostly polymorphonuclear leucocytes, stage. Here indicating that and t h e r e , t h e c a s e was s t i l l i n a b s c e s s e s of r e c e n t acute development - 1 ro­ wer e f o u n d . F arther out f r om t h e a f f e c t e d a r e a s , f ew m a c r o p h a g e s mi x e d w i t h c y t e s were found in the be p r e d o m i n a t i n g ' . a some p o l y m o r p h o n u c l e a r l e u c o ­ alveoli, yet the l a t t e r s e e me d t o The p n e u m o n i c a r e a s w e r e s p r e a d i n g q u i t e e x t e n s i v e l y and w e r e o n l y o c c a s i o n a l l y i n t e r r u p t e d by a r e a s of m ar ked c o n g e s t i o n , collapse, and emphysema. -1 9 1 Case 7 4 1 5 ( H a m p s h i r e , female) T h i s was a c a s e o f b r o n c h o p n e u m o n i a , c o m p l i c a t e d w i t h encephalitis Hi s t o r y . ( p r o b a b l y l i s t e r e l l o s i s ) a nd e n t e r i t i s . T h i s l ar ao was c o r n on 3 / 7 / 4 4 and i t s d ie d about t h r e e the days l a t e r a n i m a l wa s down on i t s ( Cas e No. side with twin 7310). sinter On 5 / 3 / 4 4 , t h e h e e d t h r o w n back e n d t h e f e e t w e r e moving; a s t h o u g h t h e a n i m a l w e r e r u n n i n g . The a n i m a l wa s t h e n k i l l e d , E t j ni p a y . A gram -negative rod from t h e l u n g s . (Table 4: (Bacterium c u l t u r e No. sjd. ) was i s o l a t e d 7415). B l o od s t u d i e s . Bl oo d p i c t u r e Erythrocytes. 8 , 9 7 0 , 0 0 0 p e r c.ram. 14,150 " " L e u c o c y t e s ..................................................... H e m o g l o b i n , . . . . ........................... 7.8 g . / 1 0 0 cc. -■ D i f f e r e n t i a l c ount ($) L y m p h o c y t e s ................................... 2 N eutrophils....„*■ ..... 9.§. ,.. ......... ... .„... ..... . s e g m e n t e r s .......................................................(78) b a n d s .................................................................... ( 18) Monocyte s ................................... 8 Eosinphils ........................ 0 B a s o p h i l s ............................................0 ( b) B l o o d c h e m i s t r y (Mgm./IOQ c c .) Glucose. .................................................1 7 0 . 0 0 U r i c a c i d ....................... ................................ S . 60 C r e a t i n i n e ..................................................... 1.30 C h l o r i d e ................. 460 . 00 N . P . N .................................................................. 4 1 . 0 0 U r e a - N ................................................................ S 3 . 3 0 The b l o od , p i c t u r e o f t h i s c a s e s h o we d a m a r k e d l e u c o - c y to s is n e u t r o p h il i a with n e u tr o p h ilic c e l l s p r e d p m in a tin g over lymphocytes (?1). ( 9 6 fo) g r e a t l y Bot h h e m o g l o b i n v a l u e -1 ??- nnci t h e n u m b e r o f e r y t h r o c y t e s w e r e somewhat l o w e r t h e n the normal v a l u e s (Table l ) , and t h e r e was s t r u c t u r e ! e v id en ce of m i c r o c y t i c hypochromis of the e r y t h r o c y t e s w i t h an o c c a s i o n a l o c c u r r e n c e of n u c l e a t e d y o u n g c e l l s . From t h e r e s u l t s o f c h e m i c a l a n a l y s i s of t h e b l o o d , the g l u c o s e was f o u n d t o be a b o u t ? . S t i m e s h i g h e r t h a n the normal s ta n d a r d whereas u r i c were e l l acid, N , P . N . , end u r e a - N s o me wh a t a b o v e n o r m a l . Gross l e s i o n s . Lungs . Tiie r i g h t e . p i c a l end c a r d i a c pneumonia" and t h e r e the process. l o b e s s h o we d " c o l d s e e m e d t o be no r e c e n t e x t e n s i o n o f In the l e f t diaphragmatic lobe, t h e r e were some s p o t s w h i c h a p p e a r e d t o be h e m o r r h a g e s . Liver . It s ho we d what a p p e a r e d t o be some c l o u d y s w e l l i n g . Brain. It seemed ed em at o u s a l t h o u g h it was q u i t e firm otherw ise. O t h e r or g a n s . Apparently normal. Microscopic l e s i o n s , Lungs. In a study of t h o s e r ig h t apical and r i g h t tissue se c tio n s taken c a r d ia c lo b e s of the lu n g s , from t h e a case of' t y p i c a l b r o n c h o p n e u m o n i a o f s e v e r a l weeks d u r a t i o n was revealed. The c h a r a c t e r i s t i c f e a t u r e s o f t h e l e s i o n we r e m etaplasia of the small bronchioles alveolar w alls general, the predominance as a r e s u l t and t h i c k e n i n g o f t h e of f i b r o b l a s t i c p n e u m o n i a wa s i n a s t a g e activity. of r e s o l u t i o n with a o f m a c r o p h a g e s c a r r y i n g on a c t i v e although groups In phagocytosis, o f p o l y m o r p h o n u c l e a r l e u c o c y t e s we r e - 1 PSobserved h ere and t h e r e in the a lv e o li In a s e c t i o n t a k e n from th e l e f t however, a different and b r o n c h i o l e s . diaphragmatic lobe, p n e u m o n i c l e s i o n was f o u n d . There w e r e some h e m o r r h a g e s i n t h i s p o r t i o n o f t h e l u n g s i n d i ­ cating th at actually result a. s t a t e existed. of a r e c e n t Th aim u s . In of hemorrhagic- b r o n c h o p n e u m o n ia T h i s c o n d i t i o n a p p e a r e d t o be t h e e x t e n s i o n of t h e the thalrnus, q u i t e a n u mb e r o f a c u t e flammatory f o c i were f o u n d . throughout areas, the c o r t e x , in­ These f o c i wer e s c a t t e r e d especially in the p e riv a sc u la r and e a c h was c h a r a c t e r i s e d by a mar ked f o c a l i n ­ filtration o f b o t h m o n o n u c l e a r and p o l y m o r p h o n u c l e a r leucocytes, constituting "perivascular cuffing". that o l d pn e u mon i c l e s i o n . a l e s i o n commonl y known a s (Fig. observed in l i s t e r e l l o s i s nervous t i s s u e , however, 44) This l e s i o n resembled and o t h e r i n f e c t i o n s . was n o t g r e a t l y The damaged s o t h a t . . u n d o u b t e d l y - t h i s wAS^ja,,case . of b e g i n n i n g : e n c e p h a l i t i s . The b r a i n w a s n o t c u l t u r e d . Liver. The l i v e r was o n l y m o d e r a t e l y c o n g e s t e d , s ho we d a m a r k e d c l o u d y s w e l l i n g and some d i f f u s e but i t fatty degenerati o n . Intestine. In the and t h e l a s t small p o r t i o n of ileum n e a r t h e a g r e a t e r p a r t of th e a f f e c t e d with i n t e s t i n e , w h i l e b o t h duodenum j e j u n u m end i l e u m we r e s e v e r e l y acute e n t e r i t i s . m u c o s a l e p i t h e l i u m was n e c r o t i c filling caecum w e r e n o r m a l A g r e a t e r p a r t of the and p a r t l y d e s q u a m a t e d , t h e i n t e s t i n a l lumen w ith in fla m m a to r y exudate w n i c h c o n s i s t e d o f d e a d t i s s u e s and some l e u c o c y t e s . -1 D 4 Summe r y and d i s c u s s i o n . 1 . Since t h i s l amb e x h i b i t e d b r o n c h o p n e u m o n i a , and e n t e r i t i s , 2. the chance fo r i t s The a n i m a l wa s s l i g h t l y organs (lungs, Apparently, presence brain, s u r v i v a l was m e a g e r . a nemi c a n d some o f t h e v i t a l liver, and i n t e s t i n e ) t h e a n i m a l was u n d e r - n o u r i s h e d . of anemia, the encephalitis, were d i s e a s e d . Due t o t h e b l o o d c h l o r i d e was a l i t t l e higher than normal. 3. The b l o o d g l u c o s e , uric Urea-N w er e a l l h i g h e r acic, creatinine, than normal, and which m i g h t r e s u l t from t h e h e p a t i c d i s o r d e r and p o s s i b l y t h e condition. N.P.N., dehydrated -1 ? 5 — Caee 7 44 3 ( S h r o p s h i r e , T h i s was a n o t h e r c a s e of bronchopneumonia c o m p lic a te d w ith Actinomyces n ecro p h o ru s i n f e c t i o n H istory. T h i s l a m b was a b o u t in the lu n g s. 64 d a y s o l d . s i c k on 5 / 1 1 / 4 4 and was b r o u g h t to t h e T h e r e was m a r k e d a b d o m i n a l b r e a t h i n g quite in a c tiv e . .male) I t was n o t i c e d pathology barn. and t h e l a m b -was The l a m b was t r e a t e d w i t h p n e u m o n i a serum f o r t wo d a y s b u t no i m p r o v e m e n t was n o t e d . The l a mb d i e d on 5 / 1 3 / 4 4 . Etiology. A gram-negative from the l u n g s r o d ( B a c t e r i u m s p . ) was i s o l a t e d ( T a b l e 4: c u l t u r e No. organism i n d i s t i n g u i s h a b l e 7443) and a m i c r o ­ f r om A c t i n o m y c e s n e c r o p h o r u s wa s a l s o i s o l a t e d f r o m t h e l u n g a b s c e s s e s . Gross p a th o lo g y . v o l v in g the Th e r e wa s a m a r k e d b r o n c h o p n e u m o n i a i n ­ apical, cardiac end a b o u t h a l f o f t h e d i a p h r a g m a t i c g l o b e s . , _ The., r i g h t a p i c a l , . , l o p e c o n t a i n e d many greenish abscesses. -1 2 6 Case 7 4 7 4 ( O x f o r d , male) This a n i m a l s u f f e r e d from bronchopneumonia c o m p l i c a t e d by c e c a l and c o l o n i c c o n s t i p a t i o n . Hi s t o r y . This a n i m a l s h o w e d s e v e r e a b d o m i n a l b r e a t h i n g a nd wa s b r o u g h t t o tr e a t e d with t h e p a t h o l o g y b a r n on 4 / 2 8 / 4 4 a n d was p n e u m o n i a s e r u m and s u l f a t h i a ? o l e . The a n i m a l s h owe d i m p r o v e m e n t and b e g a n t o e a t and n u r s e w e l l u n t i l 5/21. On t h a t day and f o r t h e f o u r d a y s f o l l o w i n g , deep a b d o m i n a l b r e a t h i n g was n o t e d and t h e abdomen b e g a n t o be d i s t e n d e d . The l amb w a s k i l l e d on 5 / 2 5 / 4 4 when i t was about 7 weeks o l d . Etiology. A g ra m -n e g a tiv e rod from th e l u n g s . (Table 4: (B a c t e r i u m s p . ) wa s i s o l a t e d . culture No. 7474) Blood s t u d i e s. ( a ) Blood p i c t u r e . 9 , 0 7 0 , 0 0 0 . p e r c. mm. E r y t h r o c y t e s . . ....................... . L eucocytes. . ) .7. ."7. .'7. 7 ; . T '" 7 , 200 - " * ' “..... H e m o g l o b i n .............................................. 10.8 g./lOO cc. D i f f e r e n t i a l c o u n t ( °J0) L y m p h o c y t e s ................................ 37 N e u t r o p h i l s .......................... 61 segmenters bands. . . . 0 Monocytes.. 1 Eosinophils 1 B asophiIs.. ( b ) Bl o o d c h e m i s t r y Glucose. . . Uric a c id . Creatinine C hloride.. N . P . N ........... Urea-N ... . ( 40) ( 21) ( Mgrn. / 1 0 0 c c . ) 88.75 2.60 1 15 3 50! 00 30.00 18.20 "" -1 P 7 - The b l o o d s t u d i e s o f t h i s c a s e r e v e a l e d t h a t f o r a m o d e r a t e l e u k o p e n i a i n which t h e p e r c e n t a g e lymphocytes ( 6 l f o) , except of ( 3 7 fo) was o u t n u m b e r e d by t h a t o f n e u t r o p h i l s t h e o t h e r c o n s t i t u e n t s of th e b l o o d d i d n o t seem t o be a f f e c t e d and d i d n o t d e v i a t e c o n c e i v a b l y normal s t a n d a r d (Tables 1 & 2 ) , Moreover, from t h e the e ry th ro c y te s wer e m o r p h o l o g i c a l l y n o r m a l and c o n t a i n e d a s u i t a b l e amount of hemoglobin. Gross l e s i o n s . Lungs. A " c o l u pneuf uoni a ,11 wa„s f o u n d i n t h e a p i c a l , cardiac a nd a s m a l l s e c t i o n o f t h e d i a p h r a g m a t i c l o b e s o f t h e r i g h t a nd l e f t s i d e s of t h e l u n g s . o f acute p r o g r e s s i o n . Intestines. with so lid , ly T h e r e was no i n d i c a t i o n R e s o l u t i o n wa s t a k i n g p l a c e . The cecum and l a r g e c o l o n wer e d i s t e n d e d dehydrated feces, edematous. and t h e mu c o s a was s l i g h t ­ Due t o c o n s t i p a t i o n , f l u i d m a t e r i a l had " b a c k e d tip s o ' t h a t b a c o n s i d e r a b l e - arnount“ o f i t wa s p r e s e n t " in the fourth Other o r g a n s . stomach. The o t h e r o r g a n s w e r e a p p a r e n t l y n o r m a l . Microscopic l e s i o n s . Lungs. A t y p i c a l b r o n c h o p n e u m o n i a wa s p r e s e n t . Most o f t h e p n e u m o n i c a r e a s w e r e d o m i n a t e d by m a c r o p h a g e s and a few- p o l y m o r p h o n u c l e a r l e u c o c y t e s w e r e p r e s e n t , t h a t r e s o l u t i o n wias t a k i n g p l a c e . Ho we v e r , indicating i n some s m a l l e r a r e a s where t h e p o l y m o r p h o n u c l e a r l e u c o c y t e s were s t i l l q u i t e numerous, t h e r e was some h e m o r r h a g e p r e s e n t . The s e a r e a s o f h e m o r r h a g e m i g h t a c c o u n t f o r some o f t h e l a t e r sympt oms o f l a b o r e d b r e a t h i n g a n d i n a c t i v i t y b u t -128w h i c h was u n d o u b t e d l y c a u s e d f o r t h e m o s t p a r t by t h e c e c a l and c o l o n i c c o n s t i p a t i o n . Kidneys. The k i d n e y s w e r e c o n g e s t e d , and some d a r k brown p i g m e n t wa s f o u n d a t t h e base of th e thelium of p a p illa e adjacent to the p e lv is . Other t i s s u e s . just stratified, epi­ The o t h e r t i s s u e s w e r e more o r l e s s n o r m a l . Summary and d i s c u s s i o n . 1 . T h i s was a c a s e o f b r o n c h o p n e u m o n i a , c o m p l i c a t e d by c e c a l and c o l o n i c c o n s t i p a t i o n . The d y s p n e a a n d s e v e r e a b d o m i n a l b r e a t h i n g i n d i c a t e d such a c o n d i t i o n . 2. The b l o o d s t u d i e s r e v e a l e d some a b n o r m a l i t i e s o f t h e b l o o d a n d t h e r e was a m o d e r a t e l e u k o p e n i a w i t h immature form s of n e u t r o p h i l i c 5. some leucocytes p resent. The l o w v a l u e o f b l o o d c h l o r i d e w a s d i r e c t l y related t o t h e pneumonic c o n d i t i o n . 4. The l a m b m i g h t h a v e been saved i f an enema h a d b e e n given in o rd er to r e l i e v e the c e c a l constipation and t h e and c o l o n i c s e r u m and s u l f a t h i a s o l e treatment renewed so as t o c l e a r up t h e pneumonic c o n d i t i o n . -1 2 9 Case 7 3 5 4 ( H a m p s h i r e , m s.le) The l a m b s u f f e r e d f r o m b a c t e r e m i a due t o P a s t e u r e l l a . infection. Hi s t o r y . T h i s c a s e a n d t h e n e x t one (Ca s e 7535) h a d t h e same h i s t o r y . 3/20/44. The l a m b s w e r e b o r n a s t w i n s a t 1 1 : 9 0 P . M . , B o t h o f t h e s e l a m b s wer e v e r y s t r o n g : a n d apparently normal. The ewe had p l e n t y o f m i l k and t h e lambs s u c k l e d v e r y w e l l even up t o 3 : 0 0 P.M., At 7 : 0 0 P.M. of the same d a y , 3/21/44. t h e s e t wo l a m e s w e r e f o u n d dead in slee p in g p o s itio n . Etiology. No. A c u l t u r e of P a s t e u r e l l a (Table 7334) wa s i s o l a t e d f r o m l i v e r , 4: culture heart-blood, and s p l e e n . Gross l e s i o n s . Skin. S u b c u t a n e o u s h e m o r r h a g e s w e r e f o u n d o v e r t h e back region. The s e h e m o r r h a g e s v a r i e d from 2 t o 10 mm. i n . . . di amet er . M u s c l e s an d f a s c i a e . L a rg e b l o t c h y hem orrh ag es were found in the semitendinosus muscle, m u s c l e s on t h e l e f t side were a l s o n o t i c e d i n th e m u s c l e s on t h e r i g h t side and a l s o i n t h e i n t e r c o s t a l of the body. fasciae Some h e m o r r h a g e s over the i n t e r c o s t a l and i n t h e f a s c ia a n t e r i o r to t h e e l bo w j o i n t s . Liver. A f ew s u b c a p s u l a r h e m o r r h a g e s we r e o b s e r v e d i n t h e l i v e r and t h e o r g a n was c o v e r e d by some w h i t i s h f i b r i n . Small i n t e s t i n e . The s m a l l i n t e s t i n e s wer e q u i t e edematous a n d t h e P a y e r ' s p a t c h e s w e r e m a r k e d l y c o n g e s t e d and edematous. The edema was s o s e v e r e patches resembled blebs. that the P e y e r ' s -1 3 0 - St o mach and s p l e e n . we r e f o u n d i n the le s s e r the P e t e c h i a l and e cc hy m otic he mor rhages stomach w a l l and u n d e r th e s e r o s a at curvature of stomach. Hemorrhages were p r e s e n t in the su b cap su lar area of the s p lee n . Omentum and p e r i - o r b i t a l f a t . P e t e c h i a l h e m orrhages were r o te d in th e se t i s s u e s . ■O t h e r f e a t u r e s . cardial, T h e r e wa s an e x c e s s o f p l e u r a l , and p e r i t o n e a l was a l m o s t c l o s e d . brain, fluids. peri­ The d u c t u s a r t e r i o s u s No h e m o r r h a g e s w e r e o b s e r v e d i n t h e a l t h o u g n t n e Dlood v e s s e l s were r a t n e r c o n g e s t e d . The h e a r t , lungs, and k i d n e y s we r e a p p a r e n t l y n o r m a l . Microscopic l e s i o n s . L iver. The l i v e r filtration s howed ma r ke d c o n g e s t i o n w i t h c e l l i n ­ and hem orrhages. The s i n u s o i d s w e r e v e r y much d is t e n d e d and f i l l e d w ith blood c e l l s . The p o l y m o r p h o n u c l e a r l e u c o c y t i c i n f i l t r a t i o n wa s r a t h e r d i f f u s e , but more c o n c e h t r a t e d a r o u n d t h e p o r t a l t r i n i t i e s . ' r h a g e s seemed t o o r i g i n a t e s p r e a d f r om t h e r e t o t h e increased in Spleen. t h e y were, The hem or-"'" from t h e p o r t a l v e s s e l s and s u r r o u n d i n g t i s s u e s and g r a d u a l l y size. The l e s i o n o f t h e s p l e e n wa s an i n t e r e s t i n g one. T h e r e was a m a r k e d s e r o s a l c o n g e s t i o n and h e m o r r h a g e s w ithout o b s e rv a b le involvement of th e or splenic pulp. In the serosa, Malpighian c o r p u s c le s the c a p i l l a r i e s i n some p a r t s w e r e c o n g e s t e d w h i l e i n most o f t h e o t h e r p a r t s they we r e e n o r m o u s l y e n l a r g e d , t i m e s as l a r g e as t h e nor mal o n e s . oeing a t l e a s t t h i r t y (Pig. 45) He mo r r h a g e t o o k -1 3 1 plsc e in th e located. a r e a s w h e r e t h e e n g o r g e d c a p i l l a r i e s wer e In th e in n e r p o r t i o n o f th e spleen, both spleen p u l p and M a l p i g h i a n c o r p u s c l e s s e e m e d t o show b u t l i t t l e if any c h a n g e s . Skeletal m uscles. congestion in in s t i l l The s k e l e t a l m u s c l e s s howed m a r k e d some p a r t s , cell in filtra tio n others necrosis hemorrhage, the and h e m o r r h a g e . in others, In the n e c ro tic muscle t i s s u e . l o s t the s t r i a t i o n s and n u c l e i and t o o k a l i g h t e r leaving ir r e g u la r In t h e p i e c e s of shrunken and crowded t o g e t h e r , s p a c e s w h i c h w e r e r e p l a c e d by c o n n e c t i v e and a d i p o s e c e l l s . These s h r u n k and c r o w d e d m a s s e s •o f dead -m u scle 'had. change d t h e i r char, a c t e r i s t i c s s t a i n e d blue stain, small i r r e g u l a r p ie c e s . s h o w i n g a mo r e a d v a n c e d s t a g e , dead m u s c l e - f i b e r s were separated The n e c r o t i c m u s c l e f i b e r s h a d w h i l e o t h e r s had b r oken i n t o tissue a r e a s of b l o o d was o b s e r v e d e i t h e r i n b e t w e e n t h e m u s c l e - f i b e r - s or i n o p e n s p a c e s f o r m e d by t h e some o f t h o s e and and,.were... i n s t e a d of p u r p l i s h pink w ith M a ll o r y 's a n ilin blue. Kidneys. The k i d n e y s w e r e r a t h e r c o n g e s t e d , h y a l i n e c a s t s were o b s e r v e d from g l o m e r u l i collecting tubules, a n d some down t o t h e i n d i c a t i n g i n c r e a s e d p e r m e e o i l i t y of the glom erular endothelium. -1 3 2 - Case 7 3 3 5 ( H a m p s h i r e , female) This a n i m a l a l s o s u f f e r e d from a c u t e bacteremia, with P a s t e u r e l l a i n f e c t i o n and t h e c o n d i t i o n was s omewhat s i m i l a r t o c a s e 7334. Hi s t o r y . Same a s Cose 7 3 3 4 . Etiology. A g r a . m - n e g a . t i v e r o d ( P a s t e u r e l l a s p . ) was i s o l a t e d from l i v e r , heart-blood, characteristics c u l t u r e Eo. of t h e and s p l e e n . For g e n e r a l e tio lo g ic a l agent, see Table 4:: 7 335. Gross l e s i o n s . The g r o s s l e s i o n s w e r e a l m o s t t h e f o r t h o s e r e c o r d e d f o r c a s e 7334 e x c e p t that same as blotchy hemorrhages were found i n th e m uscles v e n t r a l t o th e p u b i s . Microscopic l e s i o n s . Onl y a few p i e c e s p r e s e r v e d and s t u d i e d , the various o u t most o f t h e l e s i o n s t i s s u e s resembled quite . . , s er vq d i n . . . c a s e 7334..., o f t i s s u e s we r e _ __ found in closely those _ Skeletal m uscle. H e m o r r h a g e was p r e s e n t i n t h e connective and b e t w e e n t h e m u s c l e f i b e r s . tissue ob- subcutaneous The l e s i o n s were s i m i l a r to t h o s e found i n case 7334. Skin over l o i n . The s k i n o v e r l o i n r e g i o n was v e r y much c o n g e s t e d a nd some h e m o r r h a g e s we r e p r e s e n t i n t h e sub­ c u t a n e o u s t i s s u e and i n t h e mus c l e j u s t b e n e a t h . Liver. The l i v e r was s e v e r e l y c o n g e s t e d a n d s u c h l e s i o n s as cloudy s w e l l i n g , fatty degeneration, a n d h e m o r r h a g e s wer e p r e s e n t . engorged. necrotic foci, The s i n u s o i d s w e r e g r e a t l y The h e m o r r h a g e s we r e f o u n d i n t h e p a r e n c h y m a -1 3 3 - of the l iv e r as w e l l as i n the s u b c e p s u l a r r e g i o n . c l o u d y s w e l l i n g was d i f f u s e in those c e l l s out i t wa s e s p e c i a l l y The pronounced not b e in g affected, w ith f a t t y changes. F a t g l o b u l e s w e r e s e e n i n most o f t h e l i v e r c e l l s , al­ t h o u g h t h e y w e r e more c o n s p i c u o u s a r o u n d t h e c e n t r a l v e i n of each l o b u l e throughout than around the p e r i p h e r y . the l i v e r , tin y necrotic H e r e and t h e r e f o c i we r e o b s e r v e d and e a c h o f t h e m c o n s i s t e d o f a s m a l l g r o u p o f d e a d h e p a t i c c e l l s which had l o s t tecture, and t o o k a l i t t l e t h e normal c e l l s . f o c i we r e a l s o affinity for their nuclei and n o r m a l a r c h i ­ deeper hematoxylin s t e i n than The c e l l s in c lo s e c o n t a c t w i t h such a f f e c t e d a s t h e i r c y t o p l a s m s ho we d an eosin s te in and t h e n u c l e i showed p y k n o s i s . -1 3 4 - Case 7399 ( S h r o p s h i r e , m a l e ) T h i s was a c a s e o f e n t e r o t o x e r n i a . Hi s t o r y . T h i s l a m b was 3 4 d a y s o l d a n d was f o u n d d e a d on t h e morning o f 4/24/4-4. Etiology. No p r e v i o u s symptoms w e r e n o t e d . C l o s t r i d i u m w e l c h i i , Type D. Gross l e s i o n s . Thoracic c a v i t y . edema o f t h e Excess of f l u i d in the p l e u r a l c a v i t y ; lungs; ex cessiv e p e r i c a r d i a l f l u i d with f i b r i n o u s coaguTum i n p e r c a r d i a l sac; p e t e c h i a l hemorrhages on t h e t h y m u s . Abdominal c a v i t y . jejunum, B lotchy hemorrhages i l e u m and c o l o n ; (Fig. 46) c o n g estio n of P e y e r 's on t h e patches; cecum and c o l o n f i l l e d w i t h g r a y i s h l i q u i d i n g e s t a . The f o u r t h s t o m a c h was d i s t e n d e d w i t h g r o u n d g r a i n a n d coagulated milk. The k i d n e y s w e r e s o f t and m a r k e d l y congested in c e r t a i n areas. T h e r e was e x c e s s o f p e r i t o n e a l fluid. Microscopic l e s i o n s . Since some t i m e b e f o r e a u t o p s y , t h i s a n i m a l was f o u n d d e a d f o r the only t i s s u e taken s c o p i c s t u d y was s m a l l i n t e s t i n e . the fo r micro­ From t h e s e c t i o n s w h e r e b l o t c h y he m o rrh a g e s were p r e s e n t , i t was f o u n d t h a t mo s t o f t h e h e m o r r h a g e s w e r e c o n f i n e d t o t h e s u b m u c o s a l area. to The h e m o r r h a g e wa s r a t h e r be i n i t i a t e d that particular in e x t e n s i v e and i t seemed by t h e w e a k e n e d c o n g e s t e d b l o o d v e s s e l s i n region. subrnucosa w e r e g r e a t l y Moreover, the solitary l ymph n o d u l e s e n l a r g e d a n d wer e i n f i l t r a t e d by -1 3 5 - q u i t e a n u mb e r o f m a c r o p h a g e s e n d some p o l y m o r p h o n u c l e a r le u c o c y te s which fu rn is h e d another i n d i c a t i o n of in v o lv e ­ ment o f t h e P e y e r ' s p a t c h e s . (Fig. 47) -1 3 6 - Cas e 7426 (Oxford Grade, ma l e ) T h i s was a c a s e o f e n t e r o - t o x e m i a . H istory. Lapeer, T h i s l a m b came f r o m t h e f a r m owned b y Mar’ll W i l l i a m s o n , Michigan. E i g h t o r t e n of t h e l a r g e s t l a m b s h a d d i e d and t h i s w a s one o f t h e m . 3 5 - 4 0 ewes a nd t h e i r and f a t t e s t One b u n c h o f l a m b s i n w h i c h mo s t o f t h e d e a t h l o s s e s h a d o c c u r r e d was f e d a b o u t 3 / 4 b u . o f g r a i n p e r day, b u t they a p p a r e n t l y did n o t g e t enough e x e r c i s e . l a mb d i e d a t This t h e age o f a b o u t f i v e w e e k s w i t h o u t n o t i c e a b l e symptoms. Gross p a th o lo g y . Carcass in g e n e r a l. Body f l u i d s . The c a r c a s s wa s w e l l - n o u r i s h e d . T h e r e was a n e x c e s s o f p e r i c a r d i a l , pleural, and p e r i t o n e a l f l u i d s . Stomach. - ingesta. The s t o m a c h a n d rumen c o n t a i n e d d a r k c o l o r e d Some m i l k was. f o u n d i n t h e f o u r t h s t o m a c h , t h e mu c o u s me mb r a n e o f w h i c h was b a d l y Small i n t e s t i n e . congested. The P e y e r ' s p a t c h e s o f t h e s m a l l i n t e s t i n e s t o o d out d i s t i n c t l y a n d wer e s u r r o u n d e d by a ^one o f congestion. Lungs. The l u n g s we r e r a t h e r e d e m a t o u s . Other o r g a n s . C ulture. O t h e r o r g a n s wer e n o r m a l . Ne g a t i v e . C a s e s 7 4 3 4 - 13 5 - ' 3 6 These t h r e e ( B l a c k Top D e l a i n e : male, f e m a l e , mo l e ) c a s e s w e r e c o n s i d e r e d t o be e n t e r - t o x e m i a and t n e y resembled, r a t h e r c l o s e l y c a s e 74P6. -1 3 7 - H istory. T h e s e t h r e e l a m b s w e r e owned by G e r a l d F l e m i n g o f Munith, M ichigan, a n d w e r e a b o u t t h r e e weeks o l d when brought to t h e l a b o r a t o r y the larg est of on 5 / 7 / 4 4 . on t h e i r for autopsy. Th e s e l a m b s wer e t h e g r o u p o f t h e same a g e and d i e d s u d d e n l y Shortly before death, the a n i m a l s w e n t down s i d e s w i t h t h e head, t h r o w n b a c k and k i c k e d v i o l e n t l y and d i e d w i t h i n h a l f an h o u r . No p r e v i o u s sympt oms w e r e n o t i c e d . Gross p a t h o l o g y . The c a r c a s s e s wer e n o t e x a m i n e d u n t i l f o r a t l e a s t 30-4-5 h o u r s a f t e r dea. th s o t h e r e was e v i d e n c e o f post-mortem change. In g e n e r a l , the g ro ss p ath o lo g y of t h e s e l a m b s r e s e m b l e d q u i t e c l o s e l y t h a t f o u n d i n c a s e 74P6 except th a t t h e r e w e r e some e x t e n s i v e h e m o r r h a g e s on t h e e n d o c a r d i u m e n d on t h e m u c o s a l f o l d s of the f o u r th stomach. -1 3 8 - Cas e 7400 ( Rain b o u i l i e t , male) T h i s was a c a s e of a c u t e m e n i n g i t i s i n v o l v i n g m o s t l y t h e c e r e ' o r a .1 m e n i n g e s . Hi s t o r y . T h i s l a mb was b r o u g h t t o t h e p a t h o l o g y b a r n on 4/8/44 t o g e t h e r with i t s twi n and m o t h e r . The l a m b showed o i l a t e r i a l s t i f f n e s s i n t h e r e a r l e g s a n d was somewhat emaciated. The a n i m a l d i d n o t g a i n and r e m a i n e d throughout the thin o b s e r v a t i o n p e r i o d o f s h o u t two w e e k s . I t never nursed vigorously. down snd k i c k i n g i t s l e g s On 4 / 2 4 / 4 4 , t h e l a m b was a s t h o u g h i t we r e r u n n i n g . It wa.s k i l l e d when a b o u t 43 d a y s o l d . Etiology. lesion. A S t a p h y l o c o c c u s was i s o l a t e d from t h e b r a i n (Table 4: culture 7400). Blood s t u d i e s . ( a ) Bl ood p i c t u r e .... '.v. g r y t h r o c y be s . . . . . r T L e u_c o c yJ-t e s Hemoglobin D i f f e r e n t i a l count Lymphocytes NeutrophiIs segmenters. b a n d s ............. juveniles. . m yelocytes. Monocyte s EosinophiIs Basophils . . r e . u v . -.-10-,-0 70 (%) 0 0 0 ( b ) Bl ood c h e m i s t r y ( Mgm. / 1 0 0 c c . ) G l u c o s e ................ Uric a c i d . . . C r e a t i n i n e . .. . C h l o r i d e ............ N.P.N.. Urea-N. 77.77 0 . 50 0.70 15.00 9.90 ,-GOO—p e r ■-c..mm." H 'I " " 10.3 g./lO O cc. C 6 , 11 5K0Tl -1 3 9 The a b o v e d a t a showed t h a t philia existing in t h i s t h e r e was a m a r k e d n e u t r o ­ case, although the v a lu e s obtained f r om t h e b l o o d c o u n t s a p p e a r e d t o be n o r m a l . Some o f t h e e r y t h r o c y t e s w e r e c r e n a t e d . and p o i k i l o c y t i c , w h i l e w e r e more o r l e s s n o r m a l . t h e s i g n i f i c a n c e of the was b r o u g h t In t h i s instance, d i f f e r e n t i a l count for a diagn osis out. In the b l o o d a n a l y s i s , w h i c h was j u s t s little except fo r higher the g lu co se value than normal (Table o t h e r c o n s t i t u e n t s wer e d e c i d e d l y creatinine particular others lower, ?,), e l l e s p e c i a l l y the and u r i c a c i d . Gross l e s i o n s . Brain. The c e r e b r u m s h o w e d some w h i t i s h a r e a s b e n e a t h t h e meninges in th e v a r io u s Liver. sulci. L i v e r showed, some f a t t y d e g e n e r a t i o n . Other t i s s u e s . A pparently normal. .Microscopic lesions.,,. ....., ■ .. Cerebrum. The c e r e b r u m wa s v e r y much c o n g e s t e d a n d especially s o was t h e c e r e b r a l m e n i n g e s . wer e g r e a t l y The m e n i n g e s s w o l l e n and i n f i l t r a t e d , w i t h e x c e s s i v e number o f polymorphonuclear leu co cy tes and m a c r o p h a g e s . In a n u mb e r o f a r e a s t h e a f f e c t e d m e n i n g e s h a d b eco me d e t a c h e d f r o m t h e c e r e b r u m and an a c t i v e g o i n g on. The e x u d a t e o f t h i s s u p p u r a t i o n c o n s i s t e d mainly of i n f i l t r a t i n g meninges. s u p p u r a t i v e p r o c e s s was c e l l s mingled w ith the d e tach ed The g r o u n d t i s s u e was n o t much a f f e c t e d . (Fig. of the cerebrum , however, 48) Liver. The l i v e r showed some f a t t y d e g e n e r a t i o n of the diffuse type. Spiral cord. The s p i n a l c o r d and o t h e r t i s s u e s w e r e more or le s s normal. Other t i s s u e s . O t h e r t i s s u e s w e r e mor e o r l e s s n o r m a l . Summary a n d d i s c u s s i o n . 1. T h i s l a mb s u f f e r e d f r om a c u t e c e r e b r a l m e n i n g i t i s w i t h some h e p a t i c r Th r a r v i r r .a l during i t s disturbance, w re r . p , , r T' life, o ^ + -i n o an rt novor' m r iso ii v i d tit'o iirI v w h i c h c o u l d be a c c o u n t e d f o r by t h e presence of cerebral m eningitis. 3. In t h e b l o o d s t u d i e s , a state o f n e u t r o p h i l i a was f o u n d . Such a n e u t r o p h i l i a was p o s s i b l y r e l a t e d t o t h e m e n i n g ­ itis, w h e r e a s t h e h i g h v a l u e i n b l o o d g l u c o s e b u t low value in blood c r e a t i n i n e , uric acid, N.P.N., and ■ ■■■■.■- -Urea-E, •mig h t ... 8.14 ■.be ,e x p l aine_d ■p.n- 4 he.... h a s i s ...of ......hepatic d i s t u r b a n c e s and i n a c t i v i t y . -141- C a s e 7406 ( R a m b o u i l l e t , m a le ) T h i s was a c a s e o f a c u t e p e r i t o n i t i s previously Hi s t o r y . e x istin g ; bronchopneumonia. T h i s l a mb was a b o u t 45 d a y s o l d . been s i c k a b o u t three pneumonia seru m . this f o llo w in g the weeks previously For t h r e e d a y s The a n i m a l h a d a n d was g i v e n b e f o r e i t was k i l l e d , l amb h a d b e e n s h o w i n g m a r k e d a b d o m i n a l b r e a t h i n g . was k i l l e d Etiology. It on 4 / 2 5 / 4 4 . A s p e c i e s o f Cory n e ' o a c t e r i urn ws s i s o l a t e d from t h e peritoneal f l u i d and i t s f e r r e d to Table 4: general c h a r a c te r is tic s are r e ­ C u l t u r e 740 6 . Blood s t u d i e s . ( a) B l o o d p i c t u r e E r y t h r o c y t e s ..................................................1 0 , 3 9 0 , 0 0 0 p e r c.mm. 1,700 " 11 L e u c o c y t e s ...................................................... H e m o g l o b i n ..................................................... 10.3 g./lOO cc. - -, Oi X X e r e n t La 1 c oun t \ y o , Lym phocy tes...................................6 N e u t r o p h i l s ................................ 94 s e g m e n t e r s ..........................................................( 5) b a n d s ......................................................................(43) j u v e n i l e s .................................................. .. (24) m y e l o c y t e s .......................................................... (22) M o n o c y te s ....................................... 0 E o s i n o p h i l s .................................. 0 B a s o p h i l s ....................................... 0 () Blood c h e m i s t r y ( Mgm . / 1 0 0 c c . ) G l u c o s e ................... ..................................................200 .00 Uric a c i d ................................................................. 1 . 4 4 C r e a t i n i n e ...................................... 1.65 C h l o r i d e ....................................................................4-20 .00 N .P .N ........................................................................... 21 .0 0 Urea-N ........................................................................ 20.70 -14?- The r e s u l t s of blood s tu d ie s re v e a le d t h a t h a d a marked l e u k o p e n i a w i t h young n e u t r o p h i l i c ( 8 9 fo) o v e r w h e l m i n g t h e l y m p h o c y t e s of erythrocytes ( 6 fo) . t h e l amb cells The s t r u c t u r e s howed m a r k e d p o i k i l o c y t o s i s . The v a l u e o f g l u c o s e was a bou t t h r e e t i m e s h i g h e r than t h a t o f the normal ( T a b l e 2) and t h e c r e a t i n i n e was a l s o a l i t t l e The h i g h v a l u e o f u r e a - N m i g h t be d u e high. to t e c h n i c a l e r r o r . Gross l e s i o n s . Lungs. P n e u m o n i a was p r e s e n t i n t h e anterior fringe of t h e d i a p h r a g m a t i c apical, c a r d i a c and lobes. T h i s pn e u mo ni a w a s o f t h e s o - c a l l e d " c o l d " t y p e a n d t h e r e was n o a c u t e of p r o g r e s s i v e l i n e / d e m a r k a t i o n b e t w e e n t h e p n e u mo n i c a r e a and n o r m a l t i s s u e . The b r o n c h i l e a d i n g t o t h e p n e u mo n i c l o b e s were b e i n g c l e a r e d Ab d o mi n a l c a v i t y . of e x u d a t e . A m a r k e d p e r i t o n i t i s was p r e s e n t t h r o u g h ­ o u t the ab d o m in al c a v i t y . Intestines. fibrin. The i n t e s t i n e s w e r e a d h e r e d t o e a c h o t h e r w i t h The v i s c e r a l p e r i t o n e a l w a l l s a n d a d j a c e n t s t r u c t u r e s w e r e q u i t e e d e m a t o u s and s w o l l e n . Kidneys. The k i d n e y c a p s u l e was q u i t e edematous and black p i g m e n t was p r e s e n t i n t h e p e l v i s o f e a c h k i d n e y . Other o r g a n s . No v i s i b l e l e s i o n s were found i n t h e o t h e r organs. Microscopic l e s i o n s . Lungs. The l u n g s showed l e s i o n s m o n i a o f s e v e r a l weeks d u r a t i o n . of a t y p i c a l bronchopneu­ The b r o n c h i o l e s w e r e o n l y -1 4 3 - slightly d a ma g e d and some o f them s h o w e d e v i d e n c e o f m etaplasia. In the a lv e o la r w a lls, fibroblastic p r o l i f e r a t i o n going on. t h e r e wa s some In general, the p n e u m o n i a o f t h i s l a mb wa s i n a b e g i n n i n g s t a g e o f resolution a n d was n o t v e r y e x t e n s i v e , confined to c e r ta in Intestines. because i t was small spots. A ma r k e d a n d e x t e n s i v e peritonitis existed on t h e i n t e s t i n e s w i t h much i n v o l v e m e n t o f t h e s e r o s a and l e s s so f o r t h e m u s c u l a r coat. congested, thickened, (Fig. These a f f e c t e d 49) a nd became a d h e r e d t o t h e m e s e n t e r y . a r e a s w e r e i n f i l t r a t e d by polymorphonuclear le u c o c y te s . intestine The s e r o s a , wa s g r e a t l y The m u s c u l a r c o a t o f t h e was a l s o t h i c k e n e d and s ome wh a t s w o l l e n . The s u b m u c o s a a n d m u c o s a , h o w e v e r , we r e n o t much a f f e c t e d , a l t h o u g h some s e r o u s e x u d a t e was s e e n i n t h e i n t e s t i n a l l umen j u s t n e x t t o t h e m u c o s a . Liver'. The l i v e r was r a t h e r c o n g e s t e d , ' a M a r a t h e r m a r k e d c l o u d y s w e l l i n g a n d some f a t t y d e g e n e r a t i o n we r e present. an a c t i v e Along t h e s u r f a c e of l i v e r , matory p r o c e s s and n e c r o s i s w e r e in. p r o g r e s s , inflam­ the l i v e r c e l l s w e r e d e s t r o y e d a n d w e r e b e i n g r e p l a c e d by c e l l infiltration and f i b r o s i s . extended deeply in to the Some o f t h e n e c r o t i c parenchyma o f th e l i v e r v a r i e d i n s i z e from p i n - p o i n t a r e a s mm. i n d i a m e t e r . Kidneys. (Fig. processes and to those about 0 . 3- 0 . 5 50) The c a p s u l e o f k i d n e y s was s e v e r e l y i n f l a m e d and v e r y much t h i c k e n e d . The i n f l a m m a t o r y e x u d a t e wa s more or -1 4 4 - l e s s o r g a n i z e d and m i x e d w i t h t h e f i b r i n so t h a t adipose tis s u e t h e c a p s u l e became t i g h t l y and a d h e r e d t o the k i d n e y on one h a n d and t h e p e r i t o n e a l membrane on t h e other. The t h i c k e n e d c a p s u l e t o g e t h e r w i t h i t s inflammatory parts. exudate measured about 4 - 5 mm. i n some The p a r e n c h y m a o f t h e k i d n e y s , h o w e v e r , show l i t t l e o r no i n v o l v e m e n t , organized s e e me d t o a l t h o u g h t h e r e was some cloudy s w e llin g in the e p i t h e l i a l c e l l s of the convoluted tubules. Other o r g a n s . Other o r g a n s were n o r m a l . Summary and d i s c u s s i o n . 1. T h i s a n i m a l s u f f e r e d f r o m an a c u t e p e r i t o n i t i s w i t h com plication of h e p a tic disorders and r e s o l u t i n g pneumoni a . The p r e s e n c e o f b r o n c h o p n e u m o n i a a n d a c u t e p e r i t o n i t i s were r e s p o n s i b l e f o r the leukopenic n e u tr o p h ilia . l A g a i n , ' i t l a s " due “t o ' - t h e s e c o n d i t i o r i s t h a t showed d y s p n e a a t f i r s t the animal " a.nd m a r k e d a b d o m i n a l b r e a t h i n g l a t e r on w h i l e i t was s t i l l a l i v e . 3. The h i g h v a l u e i n b l o o d g l u c o s e a n d c r e a t i n i n e was d i r e c t l y r e l a t e d t o h e p a t i c d i s t u r b a n c e s as th e l i v e r was r a t h e r along i t s 4. s e v e r e l y i n f l a m e d and n e c r o t i c , entire especially surface. The C o r y n e b a c t e r i u m s p . f l u i d was p a t h o g e n i c diseased condition i s o l a t e d f r om t h e p e r i t o n e a l f o r a mouse a n d c a u s e d t h e same (acute p e r ito n itis ) when t h e organism was i n j e c t e d i n t r - p e r i t o n e a l l y . -145- C s se 7336 ( S h r o p s h i r e , fem ale) This lamb s u f f e r e d from a c u t e h e m o r r h a g i c e n t e r i t i s to g eth er with Hi s t o r y . at some p a s s i v e congestion. T h i s l a m b was b o r n a t 8 : 0 0 A.M. 3 / 2 4/ 4- 4 a n d d i e d 8 : 0 0 A.M. the next day. Shortly before death, a n i m a l was k i c k i n g v i o l e n t l y Etiology. liver, the and t r e m b l i n g . A s p e c i e s o f E s c h e r i c h i a was i s o l a t e d f r om t h e heart blood, and s p l e e n . The g e n e r a l c h a r a c t e r i s t i c s o f t h i s m i c r o - o r g a n i s m a r e r e f e r r e d t o i n T a b l e 4: culture No. 733 6. Gross l e s i o n s . l e s i o n s were A c o m p l e t e a u t o p s y was p e r f o r m e d , found, b u t no e x c e p t t h a t t h e i n t e s t i n e s were v er y much c o n g e s t e d and a n a c u t e e n t e r i t i s was s u s p e c t e d . M ic r o s c o p ic l e s i o n s . Liver. The l i v e r was r a t h e r c o n g e s t e d a nd s h o we d some small hemorrhages. The h e p a t i c cells snowed e v i d e n c e o f c l o u d y s w e l l i n g and some o f them e x h i b i t e d a s l i g h t degree of f a t t y Spleen. degeneration. T h e r e we r e h e m o r r h a g e s i n t h e s p l e e n p u l p and a moderate c o n g e s t i o n of t h e a r e a s of hemorrhage, serosal c a p illa r ie s . In the t h e l y m p h o i d t i s s u e was l a r g e l y r e ­ p l a c e d b y r e d b l o o d c o r p u s c l e s and t h e s e areas appeared deep r e d i n c o l o r w ith h e r n a t o x y l i n - e o s i n s t a i n i n con­ trast to the the spleen. l i g h t y e l l o w c o l o r of t h e normal p o r t i o n of In these a f f e c te d areas, c o r p u s c l e s were a lso in v o lv e d . the M alpighian T h e r e wer e o n l y a few -146- lymphoid c e l l s left i n each of th e c o r p u s c l e s c e n t r a l a r t e r i o l e s were g r e a t l y and the e n l a r g e d and d i s t e n d e d w ith blood. Small i n t e s t i n e . Typical l e s i o n s of hemorrhagic wer e f o u n d i n t h e s m a l l i n t e s t i n e . damaged a nd a g r e a t e r p a r t o f t h e and d e s q u a m a . t e d . enteritis The mu c o s a wa s s e v e r e l y e p i t h e l i u m was n e c r o t i c The c a p i l l a r i e s w e r e i n v o l v e d a n d hemorrhage r e s u l t e d . I n t h e lurnen o f i n t e s t i n e , an i n ­ flammatory e x u d a t e c o n s i s t i n g of desquam ated e p i t h e l i a l cells, blood c e l l s of v a r i o u s ty p e s , o f f i b r i n was p r e s e n t . and i t The s u b m u c o s a was a l s o s h owe d m a r k e d l e u c o c y t i c i n f i l t r a t i o n The m u s c u l a r c o a t s and t h e s e r o s a , affected, (Fig. ■ affected, and congestion. however, were n o t a l t h o u g h some c o n g e s t i o n was n o t i c e d i n b o t h . 51) Kidney s . ■V.. ■■•v.sjkw- e n d a s m a l l amount Hie k i d n e y s s h o w e d e v i d e n c e o f some p a s s i v e "hyp'ere'mi'a,"""'otherwi''se t h e y "wer e mo r e o r l e s s i n " ' a - n o r m a l " condi t i o n . Other o r g a n s . Those o t h e r t i s s u e s were a l l n o r m a l . included in t h i s study -147- Case 7 3 6 4 (H am pshire, m ale) This lamb s u f f e r e d fro m a c u t e e n t e r i t i s . Hi s t o r y . The l a m b was b o r n on 3 / 1 6 / 4 4 a n d was f o u n d d e a d a f ew h o u r s l a t e r . Gross p ath o lo g y . approximately No v i s i b l e sympt oms w e r e o b s e r v e d . Ther e was a m a r k e d e n t e r i t i s t wo f e e t to the rectum . from t h e p y l o r u s of t h e The rnucosa o f t h e and t h e P e y e r ' s p a t c h e s extending s t o o d out stomach e n t i r e g u t was c o n g e s t e d distinctly. The c o n t e n t s of the i n t e s t i n a l t r a c t were l i q u i d . The r e wa s a p p r o x i m a t e l y 1 0 0 c c . flu id present. of the p e r i t o n e a l T h i s f l u i d was s l i g h t l y b l o o d t i n g e d . No o t h e r v i s i b l e l e s i o n s w e r e o b s e r v e d b e s i d e s t h o s e mentioned above. Bacterial c u ltu rin g . A hemolytic gram -positive anaerobic r o d was i s o l a t e d f r o m t h e intestinal contents. -148- Ce.se 7435 ( S o u th d o w n , fem ale) T h i s wa s a c a s e o f g a s t r i c u l c e r s a n d p e r f o r a t i o n s . H istory. The l a m b was a b o u t two m o n t h s o l d . It died during t h e n i g h t o f 5 / 8 / 4 4 w i t h o u t s h o w i n g a n y p r e v i o u s sympt oms . E tiology. Un determined. Gross l e s i o n s . Upon s k i n n i n g t h e l a m b , c a r c a s s was f o u n d . A complete brain examination. The o n l y l e s i o n s f o r a t i o n of th e a well nourished a u t o p s y was d o n e , including observed were p er­ s t o m a c h a n d two d e e p u l c e r s a t t h e p y l o r u s . Microscopic l e s i o n s . The s t o m a c h r nucosa was f o u n d v e r y much congested. The m u c o s a l e p i t h e l i u m s h o we d a s l i g h t d e g r e e of n e c ro sis on t h e s u r f a c e . T h i s s l i g h t n e c r o s i s may have been due t o p o s t- m o r t e m c h a n g e s . areas, however, gastric the e n t i r e In the u lc e r a te d epithelium to g e th e r w it h the g l a n d s was s e v e r e l y damaged, a n d h a d u n d e r g o n e v a r y i n g d e g r e e s of n e c r o s i s . e x t e n d e d d e e p e r and d e e p e r , submucosa were As t h e n e c r o t i c foci t he m u s c u l a r i s m u c o s a e a n d also involved. At t h e same t i m e , ma r k e d polymorphonuclear le u c o c y tic i n f i l t r a t i o n occurred. th e l e s io n extended to th e more r a p i d l y it spread sidewise t h a n t o w a r d t h e s e r o s a s o t ha t , a g r e a t e r p a r t o f submucosa. was a f f e c t e d . w e r e d a ma g e d , submucosa, As The b l o o d v e s s e l s i n t h i s r e s u l t i n g i n hemorrhage, t i s s u e was c a l l e d i n t o action, present. the n ecro sis As a r e s u l t , the connective and a n a c t i v e g a s t r i c u l c e r i n man) s t o p p e d a t t h e area f i b r o s i s was (as i n the c ase of submucosa, b u t the -149- f i b r o s i s e x t e n d e d outward deep i n t o wh e r e m o s t o f t h e m u s c u l a r a nd a s t a t e the muscular la y e rs bund les were pushed f a r a p a r t of fibrous hy p erp lasia existed. (Fig. 5?) C a s e 7 440 ( B l a c k Top D e l a i n e , ferna.le) T h i s was a c a s e o f s t a r v a t i o n and d i e t a r y d e f i c i e n c y . Hi s t o r y . This l a mb was n o t i c e d t o be i n a c t i v e abdomen was q u i t e d i s t e n d e d . fed" calf. It and the looked l i k e a "skim-milk The a n i m a l d i e d i n t h e m o r n i n g o f 5 / 1 0 / 4 4 when 50 d a y s o f a g e . Gross p a th o lo g y . Stomach. The r umen was f i l l e d w i t h the fourth Kidneys. f i b r o u s roughage but s t o m a c h wa s e m p t y e x c e p t f o r a, s m a l l h a i r —b a l l . The l e f t k i d n e y was s l i g h t l y la rg e r than the r i g h t one a n d t h e p e l v i s o f t h i s k i d n e y was s l i g h t l y d i s ­ tended. Bones . The s k e l e t a l b o n e s o f t h i s a n i m a l we r e s m a l l e r t h a n t h o s e o f n o r m a l w e l l - f e d l a mb s o f t h e same a g e . The r i b s were e a s i l y b r o k e n . " C u ltu re Negative-* - ■■■ Cas e ?537 ■ - ------ - ( R a m b o u i l l e t , male) T h i s was a l s o a c a s e o f n u t r i t i o n a l d e f i c i e n c y , what s i m i l a r t o Hi s t o r y . c a s e 7440. T h i s a n i m a l was n o t i c e d " g o i n g l i g h t " some p a r a l y s i s some­ a n d showed o f t h e l i m b s f o r a b o u t one week b e f o r e d e a t h , which o c c u r r e d a b o u t t h r e e months of a g e . Gross p a th o 1o g y . carcass. The lamb showed v e r y fat on t h e The s k e l e t a l m u s c l e s w e r e s m a l l and n o t w e l l developed. The bo nes we r e e a s i l y with a s c i s s o r s . served, little and t h e b a c t e r i a l small, e a s ily bent, and cut No o t h e r v i s i b l e l e s i o n s wer e ob­ c u l t u r e was n e g a t i v e . -151- C ase 73PS ( R a m b o u i l l e t , m a l e ) This was a c a s e o f f a i l u r e t o d e v e l o p anal and u r e t h r a l openings. Hi s t o r y . The l a mb was t h o u g h t t o be b l o a t e d on 3 / 1 7 / 4 4 , b u t u p o n e x a m i n a t i o n i t was f o u n d t o h a v e no a n a l o p e n i n g o r u r e t h r a l opening. An o p e r a t i o n was per f o r med - w h i c h p r o ­ v i d e d f o r an a r t i f i c i a l c o u l d n o t be f o u n d . a n a l opening but the u r e t h r a Trie lamb d i e d d u r i n g t h e n i g h t of 3 / 1 8 / 4 4 and. wa s a u t o p s i e d t h e n e x t m o r n i n g . Gross p a th o l o g y Intestinal tract. The i n t e s t i n a l tra c t posterior t o t he s t o m a c h was g r e a t l y d i s t e n d e d w i t h g e l a t i n o u s f e c a l m aterial. A l t h o u g h much o f t h e m a t e r i a l h a d p a s s e d o u t , a considerable amount was s t i l l r e t a i n e d . and d i l a t a t i o n o f t h e c o l o n and r e c t u m was n o t i c e d . Bladder & g e n i t a l o rg a n s . o r g a n s were n orm a l, but The u r i n a r y A marked atony b l a d d e r and g e n i t a l t h e u r e t h r a was b l i n d due t o lack of development of th e p e n is. Other o r g a n s . No o t h e r g r o s s l e s i o n s o b s e r v e d . . -15?- (-'SSe ? 3 5 ? T h i s l amb s u f f e r e d Hi s t o r y . (R am bouillet, fem ale) from a p a t e n t foramen o v a l e . The a n i m a l was one o f a s e t o f t w i n s b o r n on 3 / ? 8 / 4 4 and was f o u n d d e a d a few h o u r s l a t e r w i t h o u t s h o w i n g any n o t i c e a b l e s y mp t o ms . Gross l e s i o n s . Ab d o mi n a l c a v i t y . Upon o p e n i n g t h e abdominal c a v i t y , the b l o o d v e s s e l s w e r e f o u n d t o be m a r k e d l y d i s t e n d e d w h i c h in d icated passive congestion. Liver. The l i v e r was i n c r e a s e d i n size a n d s h o w e d c o n­ gestion. Small i n t e s t i n e . The P e y e r ' s p a t c h e s w e r e q u i t e con­ s p i c u o u s and s u r r o u n d e d by e n g o r g e d b l o o d v e s s e l s . ^eart. The f o r a m e n o v a l e was o p e n , h e m o r r h a g e wa s l o c a t e d i n t h e r e g i o n o f one o f t h e semi l u n a r v a l v e s . Other o r g a n s . C ulture. Apparently normal. Negative. a n d an e c c h y m o t i c -153Case 7 3 9 ? ( O x f o r d , m a l e ) T h i s was s c a s e o f r u p t u r e d l i v e r . Hi s t o r y . The l amb was b o r n d e a d on 4-/90 / 44. Gross p a th o lo g y . Lungs. The l u n g s c o n t a i n e d no a i r , indicating t h a t the a n i m a l was c o r n and h a d n e v e r b r e a t h e d . Liver. ✓S, * r s V Ul + ^ V KJ The r i g h t s i d e o f t h e l i v e r wa s r u p t u r e d , o v i-ri 1 l / . W i i U A. 1i i \^. _i_ Other o r g a n s . Culture. n f i o C rli'V > n r-i + Vi *-> ^ Apparently normal. Negative. Vj C' *-< *-* "? y t V i ^ U- U * probably -154- In th e p r e c e d in g p a g e s , a to tal o f 4? c a s e s d i s e a s e s of t h e n e w -b o rn lambs has b e e n these 4P c a s e s , c o u l d not pathological findings. i s o l a t e d f r om t h e i n t e r n a l o r g a n s . t i o n as a b a s i s f o r f u r t h e r determined c a ses presented. Besides t h e r e w e r e 13 more c a s e s whose d i a g n o s e s oe made due e i t h e r t o l a c k insufficient of o f symptoms orto No b a c t e r i a wer e To f u r n i s h some i n f o r m a ­ investigations, the are p r e s e n t e d h er ew i t h i n Table Table 13 u n ­ ( 6) . (6 ) C a s e s o f d i s e a s e s of t h e n e w - b o r n l a m b s w i t h u n d e t e r m i n e d di agnosis . Ca s e No, 7303 Hi s t o r y o f t h e c a s e Southdown, f e m a l e . Bo r n on 3 / 7 / 4 4 and l i v e d only f o r about one h o u r . I t was b l o a t e d when b o r n and r e m a i n e d so d u r i n g l i f e. . , , ....... .... .... Gross p ath o lo g y F o u r t h s t o m a c h and a c c e s ­ s a r y s t o ma c h w e r e d i s t e n d e d with gas. T h e r e s eemed t o be no s t r i c t u r e e i t h e r i n th e i n l e t or o u t l e t of the s t o m a c h , and n o m o t i l e ...forma, or ba.c±er.i® w-err o b s e r v e d upon m i c r o s c o p i c e x a m in a ti o n of th e stomach contents. All other o r g a n s were a p p a r e n t l y normal. C ulture—Negative. 730 4 Southdown, f e m a l e . The l amb h a d t h e same h i s t o r y a s c a s e 7 3 0 3 but l e s s b l o a t i n th e stomach. Nothing abnormal. 730S Oxford, male. This l amb was a b o u t two days old. I t s howed n o symptoms a n d was t h e most v i g o r o u s o f the t r i p l e t ’la m b s . I t d i e d on 3 / 9 / 4 4 . No l e s i o n s . Culture—Negative. T able C a s e No, (6) (C o n t'd ) H isto ry of the case Gross p a th o lo g y 7310 Hampshire, fem ale. This a n i m a l was one o f a s e t o f t w i n s w h i c h wa s b o r n on 3 / 7 / 4 4 . The l a mb a p p e a r e d weak and d i e d a t t h e age o f t h r e e d a y s E x c e p t some p a r t i c l e s o f f i b r i n on t h e s u r ­ f a c e o f l i v e r , no o t h e r l e s i o n s were found. 7311 H a m p sh ire , m a l e , about 3 days old. The l amb was n o t i c e d b r e a t h i n g h e a v i l y and p n e u m o n i a was s u s p e c t e d . I t was t h e n t r e a t e d w i t h pneu­ m o n i a serum and s a l i n e a n d g l u c o s e ( 5ejo) . I t d i e d on 3 / 1 0 / 4 4 . Extensive subcutaneous h e m o r rh a g e s were found in th e v i c i n i t y of o o t h h i n d l e g s , and m a r k e d h e m o r r h a g e was found i n t h e g a s t r o c ­ nemius m u sc le s . The ductus a r t e r i o s u s showed a s m a l l o p e n i n g . O t h e r o r g a n s wer e a p p a r e n tly normal. Culture—N egative. 7321 S o u t h s own, ma l e , a b o u t 24 h o u r s o l d . This l ar nb was b o r n b l o a t e d on 3 / 1 ? / 4 4 and l i v e d o n l y f o r a few h o u r s . I t had a h i s t o r y s im i­ l a r to cases 7303-'04 S u b c u t a n e o u s h e mo r ­ r h a g e s were p r e s e n t along th e l e f t side o f t h e b a c k l i n e from the s h o u ld e r to the t a i l region. No f o o d was p r e s e n t i n t h e ,s.t oma c h . Th e,, s t pmach was d i s t e n d e d w i t h gas to th e p o in t where i t r e a c h e d the pubis. No o t h e r v i s i b l e l e s i o n s wer e found. 73?? Oxford, fem ale. This l a m b wa s weak and. h a d b e e n g i v e n 90 c c . o f s a l i n e and g l u c o s e ( 5 fo) p r e v i o u s t o d e a t h I t was f o u n d d e a d on 3 / 1 4 / 4 4 when s i x d a y s No v i s i b l e l e s i o n s we r e o b s e r v e d . Culture—Negative. Old . -156Table (6) (C o n t'd ) Case No. H is to ry of the case Gr os s p a t h o l o g y 73 ?5 Southdown, m a l e . This l a m b was b o r n a t 5 : 0 0 A. M. , 3 / 1 5 / 4 4 . I t was s t i f f a t b i r t h and made no e f f o r t t o move. 80 c c . o f s a l i n e g l u ­ c o s e (5/o) w e r e g i v e n s u b c - u t a n e o u s l y and 4 o z . o f c o l o s t r a ! milk, f r o m t h e ewe o r a l l y . The lamb d i e d when i t wa s a b o u t two days o l d . No v i s i b l e l e s i o n s were fo un d e x c e p t a s l i g h t edema o f t h e stomach w a l l . Culture— Negative. 7354 Rambnuillet.. fem ale. T h i s l amb was b o r n on 3 / 1 4 / 4 4 and was g r a d e d a s l - A a.t b i r t h , with­ o u t any n o t i c e a b l e s y mp t o ms , t h e a n i m a l d i e d a t t h e age o f a b o u t PO d a y s . No g r o s s l e s i o n s were o b s e r v e d . C ulture— Negative. 7367 S h ro p sh ire, male. The Spleen. The s p l e e n l a mb was b o r n a s one o f showed many p e t e c h i a l a p a i r o f t w i n s on he m or rh ag es under t h e 4 / 9 / 44 . and wa s f o u n d capsule. deed s h o r t l y a f t e r H e a r t . One p e t e c h i a l " b i r t h n - ' — ■■■ ■ ■... ■ “hemorrhage- was found.- ■ under the epicardium. The d u c t u s a r t e r i o s u s was o p e n a s woul d be expected. Lu ngs . Only p a r t l y expanded, i n d i c a t i n g t h a t t he l a m b l i v e d fo r a very short time. Stomach. A few p e t e c h i a l hemorrhages wer e p r e s e n t on t h e f o ld s of stomach. Ot h e r o r g a n s . A p p a r e n t ly normal. C u l t u r e — Ne g a t i v e . 7388 S h ro p s h ir e , female. T h i s l amb was a b o u t f i v e d a y s o l d and d i e d on 4 / 1 8 / 4 4 w i t h ­ o u t any n o t i c e a b l e sympt oms. No o t h e r v i s i b l e l e s i o n we r e o b s e r v e d e x c e p t a few s u b c u t a n e o u s hemorrhages in the v i c i n i t y of the t a i l head. C u ltu re--N egative. -157- Table ( 6 ) ( C o n t ’ d) Gross p a t h o l o g y C a s e No. H i s t o r y of th e case 7 ?83 Ham pshire, m a le, about 3 days o ld . The l amb became d r o o p y on t h e a f t e r n o o n o f 3 / 1 / 4 4 and d ied the next morning. No g r o s s l e s i o n s we r e found. Culture—Negative. 7P04 3 h r o p s iii r e , f e ma l e , a b o u t P4 h o u r s o l d . T h i s l ame was one of' a s e t of t r i p l e t s . It was a s m a l l l a m b and d i e d on 3 / ? / 4 4 w i t h o u t any n o t i c e a b l e symptoms No l e s i o n s o f t h e i n t e r n a l organs were observed. C ulture— Negative. -1 5 8 - I V. Fifty-five D is c u s s io n of R e s u l t s c a s e s of new -b orn lambs a f f e c t e d , w i t h a v a r i e t y of d is e a s e s were included in th is study and t h e p r o b l e m was a t t a c k e d h e m a t o l o g i c a l l y , b e c t e r i o l o g i c a l l y , and p a t h o l o g i c a l l y . Tne h e m a t o l o g i c a l i n v e s t i g a t i o n the co n sisted of studying b l o o d f r o m Dot h n o r m a l s h e e p a n d p a t h o l o g i c a l lambs. The b l o o d v a l u e s o b t a i n e d f r om n o r m a l s h e e p s e r v e d a s a c o n t r o l . The r e s u l t s are briefly summarised in T a b le s (1, 2 , 3) and d iscu ssed in d e t a i l in connection with the i n d i v i d u a l cases. For t h e sake of co m p a r i s o n , t h e r e s u l t s r e c o r d e d by a number 1 ?9 4^ o f o t h e r w o r k e r s s u c h a s A l l c r o f t , F r a s e r ' , Hol man 45 75 91 J o s i a n d " , N o r r i s and C h a m b e r l i n , and S h e a r e r and S t e w a r t " we r e c o n s u l t e d . In g e n e ra l, the r e s u l t s o f blood s t u d i e s on n o r m a l s h e e p c o mp a r e f a i r l y w e l l w i t h t h o s e o f o t h e r w o r k e r s e x c e p t some mi n o r d i f f e r e n c e s . found the t o t a l Norris and C h a m b e r l i n a v e r a g e o f w h i t e b l o o d c o r p u s c l e s f o r l a mb s t o b e 5, 5 1 0 ' p e r c , rhm. ""'as''corn p a r e d t o "7,' 979 "per'^'c .'mm'l f or " our normal lambs. The n e u t r o p h i l s w e r e 57 p e r c e n t p a r e d t o o u r f i n d i n g o f 30 p e r c e n t i n s h e e p . a s com­ The b l o o d g l u c o s e v a . l u e s f o r s h e e p w e r e h i g h ( 7 5 mgm. fo a s c o m p a r e d to oui' 4 8 . 4 3 ragrn. fo ) . l a m b s were h i g h In F r a s e r ' s work, the n e u t r o p h i l s of ( 5 4 $ a s c o m p e r e d t o o u r r e c o r d o f 7 8 fo ) . T h i s may be due t o a l a c k o f u n i f o r m i t y among t h e v a r i o u s workers, in conditions. the technics used, and t o d i f f e r e n t environmental R e g a r d i n g t h e s tu d y o f blood i n d i s e a s e d lambs, no p r e v i o u s r e f e r e n c e s w e r e a v a i l a b l e f o r making a co m p a r i s o n . '■*!o r k o f t i i i s k i n d i s c o m p a r a t i v e l y new t o t h e f i e l d v e te rin a ry medicine. of -159- In the b a c t e r i o l o g i c a l studies, 4-1 c u l t u r e s o f a e r o b e s and 7 a n a e r o b e s w e r e i s o l a t e d from v a r i o u s c a s e s . of m o r p h o l o g i c a l , these biochemical, a nd p a t h o g e n i c i t y t e s t s , c u l t u r e s were i d e n t i f i e d They w e r e : Staphylococcus, Escherichia, and g r o u p e d u n d e r Eacterium, P a s te u r e lla , Staphylococcus, 9 genera. Diplococcus, N e isse ria , A c t i n o m y c e s and C l o s t r i d i u m . Bacterium, By means Corynebacterium, Two c u l t u r e s wer e u n d e t e r m i n e d . and P a s t e u r e l l a were most f r e ­ quently encountered, while N eisseria and t h e u n d e t e r m i n e d c u l t u r e s were e n c o u n t e r e d t h e l e a s t number of t i m e s . Twent y ( 4 8 . 7 8 'jo) o f t h e 41 o r i g i n a l a e r o b i c c u l t u r e s w e r e r e ­ c o v e r e d f r om i n o c u l a t e d m i c e , definitely virulent. to the c u l t u r e s (Table 4). 13 ( 3 1 . 7/s) o f w h i c h w e r e R a b b i t s wer e f o u n d t o be q u i t e i s o l a t e d f r o m l a m b s and w e r e n o t resistant suitable for pathogenicity te s ts . The p a t h o l o g i c a l and b a c t e r i o l o g i c a l 15 d i f f e r e n t t y p e s o f d i s e a s e s among t h e were: White-muscle d is e a s e , infection, docking in f e c tio n , pneumonia, pasteurellosis, itis, enteritis, deficiency, studies revealed 55 c a s e s . They staphylococcic in fe c tio n , c a s t r a t i o n wound, broncho­ enterotoxemia, m en in g itis, gastric ulcers co n g en ital anomalies, navel end p e r f o r a t i o n , periton­ dietary and a n u n d e t e r m i n e d g r o u p . Most o f t h e s e d i s e a s e s w e r e s t u d i e d mo r e o r l e s s in d e ta il, and t h e f o l l o w i n g d i s e a s e s o r c o n d i t i o n s s u c h a s c o n g e n i t a l interstitial bronchopneumonia, p a te n t p a t e n t foramen o v a l e , gastric ulcers ductus a r t e r i o s u s , and p e r f o r a t i o n , a-* ('Q 4 U to t h e w r i t e r . lesions "^4 cm 4. u i f t /*> V ^ V ' -/—> U i; c_/ .L c h w p "1 4 p n r.« j l 4* 4 <0* U j_ v From m i c r o s c o p i c in th e thalm us (so-called "pericasculor c u f f i n g s ") w e r e somewhat s i m i l a r t o t h o s e f o u n d i n c a s e s 31 47 o f o v i n e l i s t e r e l l o s i s r e p o r t e d by G i l l , Jungherr , 8 34 81 Bi e s t e r and S c ' n war t e , Graham e t a l , P ellaske , and 83 Pomeroy e t e.l . The b r a i n was n o t c u l t u r e d i n t h i s p a r t i c u l a r c a s e . t h e i ef ox e t h e e t i b l d g f e e l a g e n t ’was^ h o t " " d e t e r m i n e d . 4• Br on c-n o pn e um on i a ( 1 5 c a s e s ) B r o n c h o p n e u m o n i a i s common i n ne w-born l a m b s . the lambing season l a s t y e a r bronchopneumonia encountered, p During ( 1 9 4 4 ) , a b o u t 15 c a s e s o f ( e i t h e r wi th or w i t h o u t c o m p l i c a t i o n ) were a n d most o f them w e r e o f t h e a c u t e t y p e . Quite v a r i e t y o f m i c r o - o r g a n i s m s were i s o l a t e d from t h e a f f e c t e d lungs, such a s : D iplococcus, Actinomyces n e c r o p h o r u s , Bacterium , Escherichia, N eisseria, Pasteur e ll s . , and Staphylococcus. Th e s e f i n d i n g s a g r e e q u i t e w e l l w i t h t h o s e 95 63 P 2 an ^ 49 o f S p r a y 1 ' . Met tern , D e l p y ' ~ , / K o s h e l e v , although '■ -16?- Ac- t i nomyces n e c r o p h o r u s i s a s one o f t h e c a u s a l a g e n t s i n l amb p n e u m o n i a . r e s u l t s of the s e e ms t h a t repo rted here fo r the f i r s t present a nd p r e v i o u s time Taking the investigations, it t h e c a u s a l a g e n t s of lamb pneumonia a r e v a r i a b l e and n o t s p e c i f i c . 5. Na v e l , These t h r e e doc k i n g , and c a s t r a t i on i n f e c t i o n s . different types of i n f e c t i o n are d i s c u s s e d t o g e t h e r , b e c a u s e t h e y a r e mo r e o r l e s s d u c e d by u n s a n i t a r y t e c h n i c s , n o v e l and i n s a n i t a r y la st year (1944), Bacterium, coccus), surroundings. In Corynebacterium, pro­ of the the lambing season and 1 c a s e o f c a s t r a t i o n The c a us a ] , o r g a n i s m s like specific. improper d i s i n f e c t i o n 5 cases of navel in fe c tio n , docking i n f e c t i o n , encountered. artificially ? cases of i n f e c t i o n were ( A c t i n o m y c e s n e c r o ph o r u s , C o c c o i d o a c i l l u s and S t a p h y l o ­ in pneumonia,were a lso v a r i a b l e and n o t T h e s e d i s e a s e s w e r e m e n t i o n e d and d i s c u s s e d by many w o r k e r s i n trie "Tib Id""'of v e t e r i n a r y research" lo n g ago," ”■ cut they s t i l l re main s g r e a t problem t o the s h e e p i n d u s t r y . In o r d e r t o p r e v e n t mor e a t t e n t i o n such l o s s e s , it s e e m s n e c e s s a r y t o pay to aseptic surgical operations, disinfection s r d e n v i ronm e n t . °• Per i t o n i t i s Cases of p e r i t o n i t i s by C r a i g and B i t t i n g ?] ir. l a m b s w e r e the case attention. of acute briefly i n 1 9 0 ? and cy G a l l a g h e r No c a u s a l a g e n t s w e r e m e n t i o n e d . tion, (7406) discussed 30 i n 1 9? 1. In the present in v e s tig a ­ peritonitis ( c a s e 7406) n e e d s s p e c i a l The c a u s a l a g e n t was a. s p e c i e s o f p l e o - m o r p h i c -163- grsm-positive diphteroid ( Corynebacterium) l e s i o n s wer e b e a u t i f u l l y presented. Pasteurellosis and t h e t y p i c a l ( C a s e s 7 334- & 7 335) Six c u l t u r e s of P a e t e u r e l l a were i s o l a t e d from v a r i o u s organs of p a t h o l o g i c a l lambs, 7 33 5) we r e c o n s i d e r e d t o out o n l y two c a s e s be t h e t y p i c a l (7334 & pasteurellosis. T n e s e two c a s e s vse r e found i n a p a i r o f t w i n l a mbs b o r n on 3 / 3 0 / 4 4 - and w h i c h d i e d t h e n e x t d a y . c h a ra c te r is e d , as an acute w e r e f oun d i n The d i s e a s e was b a c t e r e m i a and b l o t c h y h em o r rh ag es subcutaneous t i s s u e and m u s c l e s i n b o t h c a s e s . 1-1 Q S i n c e P a s t e u r e l l o s i s was r e p o r t e d oy Caz e , o c c u r r i n g a s an e p i z o o t i c among A l g e r i a n s h e e p , t h i s g i v e s t h e w r i t e r a clear-cut impression th a t P a s te u r e llo s is needs s p e c i a l i n n e w - b o r n l a mb s attention. 3. Two c a s e s Staphyl ococcic i n f e c t i o n . (7337-33) d uring the course of t h i s s t a p h y l o c o c c i c i n f e c t i o n were found study. The d i s e a s e wgg c h a r a c t e r i ? : e d by a c u t e s e p t i c e m i a a s s o c i a t e d w i t h m e t a s t a t i c n e c r o t i c foci and a b s c e s s - f o r m a t i o n w h i c h a g r e e s q u i t e c l o s e l y w i t h . 16 , t h e c o n d i t i o n r e p o r t e d by b u l l a r o (1934). 9. E n t e r o t ox e mi a ( C a s e s 7 399, 7 4 9 6 , 7434, 7 435, 7436) Five c a s e s o f e n t e r o t o x e m i a were e n c o u n t e r e d d u r i n g t h e c o u r s e of t h i s the study , which i n d i c a t e s t h a t young lambs have same c o n d i t i o n as s e e n i n o l d e r s h e e p and f e e d l o t l a m b s , although the f e e d and e n v i r o n m e n t a r e d i f f e r e n t . • Unde t e rm i n e d c a se_s . A g r o u p o f 13 u n d e t e r . n i n e d c a s e s was f o u n d d u r i n g t h e -1 6 4 c o u r s e of t h i s study. The c a u s e o f d e a t h i n t h e s e cases v;ps n o t d e t e r m i n e d and no g r o s s l e s i o n s w e r p o b s e r v e d . This group p r e s e n t s a c h a l l e n g e to e x p e r i m e n t a l i n g e n u i t y . White-muscle disease Two c a s e s (7356-58) ( C a s e s 7656-58) of w h i t e - m u s c l e d i s e a s e were en­ countered during the course of t h i s study. One ( C a s e 7358) o f t h e s e t wo c a s e s was c o m p l i c a t e d b y b a c t e r e m i a , l e a d i n g to e b s c-es s-fo rm atio n and a r t h r i t i s , was n o t . bacteria In the com plicated case, (« S t a p h y l o c o c c u s , c o c c u s and a D i p l o c o c c u s ) w h ile the o th e r ( Ca s e 735 6 ) th re e d i f f e r e n t kinds of an u n d e t e r m i n e d g r a m - p o s i t i v e were i s o l a t e d , w h e r e a s i n t h e un­ c o m p l i c a t e d o r t y p i c a l c a s e no b a c t e r i a l f o r ms w e r e f o u n d . Apparently, case of w hite-m uscle a typical (or uncomplicated) d i s e a s e i s n o t c a u s e d by any b a c t e r i a l i n f e c t i o n , and t h a t a g r e e s v e r y w e l l w i t h t h e wor k o f t h e hew York ( C o r n e l l ) 6 4 , 7 3 , 10 5 79 Station a n d t h e Or egon S t a t i o n . On t h e o t h e r ZLA h a n d , ' J u n^i t i r e n d 'Welch"'"’* f o u n d ' coc-cibia i n -case' s’""of' 38 "stiff-lam b d i s e a s e , Heath f o u n d an a c i d - f a s t b s c i x l u s i n a s i m i l a r d i s e a s e d c o n d i t i o n , w h i l e Lee & S c r i v n e r i s o l a t e d 3 k in d s of b a c t e r i a spore forming ro d s) (bipolar rods, 50 c o c c i , and n o n ­ from l a m b s w i t h t u i s m a l a d y . The r e s u l t s o f t h e p r e s e n t i n v e s t i g a t i o n a s i l l u s t r a t e d b y Cas e 7358 clearly actually indicate that this l a t t e r g r o u p o f w o r k e r s were d e a lin g with whit e-muscle some o t h e r i n f e c t i o n . d i s e a s e c o m p l i c a t e d by The b l o o d s t u d i e s on w h i t e - m u s c l e d i s e a s e r e v e a l e d hig h v a l u e s i n a l l s i x blood c o n s t i t u t i o n s - -1 6 5 st-udied which a g r e e d r a t h e r differences, with In th o se c lo s e ly , except f o r minor the f i n d i n g s of Anderson two c a s e s a b o v e , no c a r d i a c (7356-58) 9? SholT . and s t u d i e d and p r e s e n t e d i n v o l v e m e n t s we r e f o u n d . h o w e v e r , t h e w r i t e r h a d an o p p o r t u n i t y wnite-muscle 3 Just recently, to study a c a s e of d i s e a s e i n s y o u n g l e m b ( C a s e 6598) department c o l l e c t i o n . from our The p a t h o l o g i c a l p r o c e s s e s i n t he h e a r t follow ed r a t h e r c l o s e l y those found in th e s k e l e t a l m u s c l e out m o r e m i t o t i c i n g muscle c e l l s (Fig. were se en (Fig'. 54). f i g u r e s were n o t e d i n t h e r e g e n e r a t ­ 53) ana s m a l l e r muscle g i a n t The c e l l w i t h t h e m i t o t i c cells f i g u r e or w ith the s o - c a l l e d " p e c u lia r nu clear s t r u c t u r e " found in t h e h e a r t was f i r s t d e s c r i b e d by A n i t s c h k o w i n 1 9 1 3 and 1 S0 was c a l l e d t h e " A n i t s c h k o w m y o c y t e " . Anitschkow b e l i e v e d th a t these c e l l s o r i g i n a t e d in the muscle f i b e r s of the h e a r t b u t t h i s o b s e r v a t i o n was d i s r e g a r d e d by E h r l i c h and IQa 19a Ixapan~r -hirv 1-.9 3Q- a.nd-Glsw-son . a.nd,-.,.Dow.ne-y -- ■••■-in'. 19-41-. E h r l i c h and L a p a n wer e c o n v i n c e d t h a t this the i n t e r s t i t i a l and c a l l e d i t tissues of the h e a r t c e l l a r o s e from a " m y o c a r d i a l r e t i c u l o c y t e " w h i l e Cl aws o n and Downey t h o u g h t it s h o u l d be c a l l e d a " c a r d i a c h i s t i o c y t e " "reticulocyte" it is applied to a red blood c e ll. h a s been g e n e r a l l y interstitial fibers. s in c e t h e term tissue agreed that i t and n o t develops Since then, f r om c a r d i a c f rom t h e m y o c a r d i a l m u s c u l a r Boyd 1 3 d e s c r i b e d t h i s c e l l a s "a c a r d i a c h i s t i o c y t e w n i c h i n i n f l a m m a t i o n shows i n c r e a s e d c y t o p l a s m . , characteristic a highly s e r r a t e d b a r of c h r o m a t i n in th e c e n t e r of *1 n r» -lo o — the nucleus, and f i b r i l s r a d i a t i n g f r om t h e b a r t o t h e periphery." Apparently, Boyd d i d n o t n o t i c e t h a t "peculiar nuclear structure" beautiful m itotic figure the was n o t h i n g more t h a n a (probably in the metaphase stage) i n an a c t i v e l y - p r o l i f e r a t i n g r e g e n e r a t i n g m u s c l e c e l l i n the h e a r t. In f a c t , cells o f such k i n d , p o i n t e d o u t by E h r l i c h and La p a n observed in rheum atic fever pathologic s ta t e s , ] 9a in the h e a r t , as , we r e n o t o n l y f r e q u e n t l y b u t a l s o i n a number o f such as s e p s i s , Rcprlet fever, p e r i c a r d i t i s nodosa, endocarditis. Undoubtedly, meningococcic bacterem ia, and s u b a c u t e b a c t e r i a l certain regenerating cardiac m u s c l e c e l l s w i t h m i t o t i c f i g u r e s may be e x p e c t e d u n d e r t h o s e conditions. An o t h e r i n t e r e s t i n g but important p o i n t s h o u l d b e men­ tio n e d here in r e g a r d to r e g e n e r a t i o n of h e a r t m u s c l e . stated t h a t " p l a i n muscle and h e a r t m u sc le f i b e r s Boyd''' do n o t • r e g e n e r a t e ; - u n i o n . o f ' t h e d i v i d e . d parte-...is....by s c a r , - t i ssue- " Fro.a t h e r e s u l t s of present, i n v e s t i g a t i o n i t h e a r t muscle h a s th e a b i l i t y certain conditions Moreover, s eems t h a t t h e to r e g e n e r a t e a t l e a s t under (white-muscle d isea se i n l a mb c a s e 6 5 9 8 ) . s i n c e t h e s o - c a l l e d " A n i t s c h k o w m y o c y t e s w e r e ob­ s e r v e d i n a riumoer o f p a t h o l o g i c c o n d i t i o n s o f t h e h e a r t by E h r l i c h and L a p a n 1 0 8 and i n Iieart) syphilitic m y o c a r d i t i s (gumma o f 13 SQ 76 a s r e p o r t e d by many o t h e r w o r k e r s ' ' , further e v i d e n c e was f u r n i s h e d t o s u b s t a n t i a t e the fa c t th a t cardiac m u s c l e m i g h t a l s o r e g e n e r a t e u n d e r some o f t h e s e c o n d i t i o n s . - -167- The h i s t o - p a t h o l o g y o f w h i t e - m u s c i e d i s e a s e i n l ambs was b r i e f l y worked, o u t f i r s t by M e t z g e r end Ha g a n 0 ' i n 1 9 ? 7 , They me n t i o n e d , f o u r ma i n p o i n t s , n a m e l y , (l) w hitish or p a t c h e s as t h e g r o s s l e s i o n in t h e m u s c l e ; d e g e n e r a t i v e and not in fla m m a to r y ; infiltration (A) of the p r e s e n t practically e p h a g o c y t i c c e l l was f o u n d . investigation no c e l l The r e s u l t s A p p a r e n t l y , M e t z g e r and Hagan d i d n o t n o t i c e muscle; g i a n t c e l l s vital is agree in c e r t a i n r e s p e c t s with f in d in g s but not in a l l . activities it by p o l y m o r p h o n u c l e a r o r o t h e r w a n d e r i n g c e l l s ; occasionally their ( 3) (£) streaks nor the p r o l i f e r a t i v e of t h e r e g e n e r a t i n g muscle c e l l s which a r e so and s i g n i f i c a n t particular disease. to the p a t h o l o g i c a l p r o c e s s e s of t h i s F o l l o w i n g M e t z g e r and Hagan, number of r e s e a r c h w o r k e r s , 46 , members 77 of t h e V e t e r i n a r y R e s e a r c h L a b o r a t o r y o f Or egon S t a t i o n , 38 60 93 Heath , Mars h , S l e g s v o l d and L u n d - ^ a r s o n ' , Lee e n d .,'"=.38.... 85 1Q5- 111 ... cy)-.... -.......... Scrivner" , S c h o lfie ld , Sal yi . , and if i l i m a n e t a l , wer e a c t i v e l y engaged i n studying- the p a t h o l o g i c a l of the d i s e a s e . made t o w a r d t h e exists. It J u n g h e r r a n d Y/elch quite a Up t o t h i s solution s e e ms r a t h e r of moment, l i t t l e the problem, aspect a d v a n c e h a s been and. c o n f u s i o n s t i l l strange th a t not a single worker has d e s c rib e d the microscopic le s io n s in the h e a r t . To s t a t e briefly, th e h i s t o - p a t h o l o g y of w h i t e - m u s c l e d i s e a s e in v o lv e s m yodegeneration f o llo w e d by m y o -re g e n e ra tio n . In t h e d e g e n e r a t i v e c h a n g e s , the im p o rta n t f e a t u r e is hyalina- t i o n o f t h e a f f e c t e d m u s c l e f i b e r s t o g e t h e r w i t h some -168- fibroblastic activity, w h ile in the r e g e n e r a t i v e p r o c e s s , the n u c le a r p r o l i f e r a t i o n from the u n a f f e c t e d musc le f i b e r s o r from t h e s u r v i v e d s a r c o l e m m a l e a d t o t h e f o r m a t i o n o f muscle g i a n t c e l l s and r e g e n e r a t i n g m us cl e f i b e r s . fu n c tio n of the muscle g i a n t c e l l s i s tis s u e s while The t o r emove t h e d e a d t h a t of r e g e n e r a t i n g muscle f i b e r s i s to f i l l t h e g a p s l e f t by damaged t i s s u e . If the damage wa s so s e v e r e t h a t t h e a f f e c t e d m u s c u l a r n u c l e i wer e d e a d , blastic proliferation and s u b s e q u e n t f i b r o s i s would t a k e p l a c e and t h e l e s i o n wo u l d b e f i l l e d w i t h f i b r o u s tissue. In the heart, t h o s e found i n t h e in the le s io n s s k e l e t a l muscle the r e g e n e r a t i n g muscle fibro­ and adipose a r e somewhat s i m i l a r t o b u t mor e m i t o t i c figures f i b e r s and s m a l l e r g i a n t c e l l s were observed. R e g a r d i n g t h e s u b j e c t o f " m y o d e g e n e r a t i o n and myoregeneration" in general, it was n o t i c e d t h a t many w o r k e r s i n ’ t h e '"field' o f p a t h o l o g y H a v e b e e n a c t i v e l y ' engaged, i n s u c h ] 0] a study. As e a r l y a s 1 8 6 ? , Vi r c h o w" " was a b l e t o f i n d t h e so-called muscle. " r e p a i r clubs of s t r i p e d muscle" in r e g e n e r a t i n g He m e n t i o n e d t h a t s embl ed. m y e l o p l a x e s . these r e p a ir clubs c lo se ly r e 51 In 1899, L e j a r s and h i s f r i e n d F i l l e t d e s c r ib e d t u b e r c u l o s i s of t h e muscle w ith form ation of m ultinuclested g ia n t-c e lls from t h e s t r i a t e d f i b e r s . t h e i r d e s c r i p t i o n was b r i e f a n d p o o r l y i l l u s t r a t e d drawing), t h e i r wor k h a s l o n g b e e n d i s r e g a r d e d . L e j a r s and h i s Since (hand Moreover, f r ie n d did not a p p r e c ia te the s ig n i f i c a n c e of the g ia n t c e l l in t u b e r c u l o s i s m uscle, because th e y did n o t know t h e e x a c t f u n c t i o n o f t h e c e l l a n d p r o c e s s of i t s -139- formation. I n 1 9 0 1 , Mere h a n d 37 m e n t i o n e d such " r e p a i r c l u b s o f s t r i p e d m u s c l e s " and i n c l u d e d t hem among t h e s o u r c e o f f o r e i g n body g i a n t c e l l s . 55 M a l l o r y " ' t 19 1 4 , e x p l a i n e d t h e v a r i o u s a p p e a r a n c e s o f i n j u r e d s t r i p e d m u s c l e a nd s t a t e d t h a t fib er is k ille d , it "when t h e w h o l e m u s c l e is not regenerated. one o f t h e f i b e r s i s d e s t r o y e d , When o n l y a c t i v e r e g e n e r a t i o n of the p a r t wh i c h h a s n o t u n d e r g o n e n e c r o s i s t a k e s p l a c e p a r t wnich r e m a i n s u n i n j u r e d . rapid a p a r t of f r om t h e The i n t a c t n u c l e i u n d e r g o d i r e c t d i v i s i o n a nd e a c h f o r m s s e v e r a l d o z e n s e p a r a t e n u c l e i ............... The new n u c l e i m i g r a t e t o t h e p e r i p h e r y and t h e i n j u r e d e n d o f t h e m u s e l e - f i b e r ................... The p r o c e s s of r e g e n e r a t i o n o f m u s c l e - f i b e r s i s c o m p l i c a t e d and made c on ­ f u s i n g by t h e p r e s e n c e o f n u m e r o u s l e u c o c y t e s a t t r a c t e d by the in ju rio u s a g e n t and by t h e i n j u r e d t i s s u e . S o me t i me s t h e n e c r o t i c m u sc le i s removed t h r o u g h t h e a c t i o n o f p o ly ­ m o r p h o n u c l e a r l e u k o c y t e s , w h i c h u s u a l l y ‘I n v a d e t h e f i b e r s ; ......* ............... b u t a t o t h e r t i m e s o n l y e n d o t h e l i a l l e u k o c y t e s a r e present. They a t t a c k n e c r o t i c m u s c l e s u b s t a n c e p e r i p h e r y and g r a d u a l l y without inward. dissolve i t , Mitoses in a r e not, i n f r e q u e n t . working s low ly from these e n d o th e lia l leu c o c y te s O c c a s i o n a l l y , m u l t i p l e m i t o s e s occur f r o m whi c h m u l t i n u c l e a t e d c e l l s r e s u l t . the f r om t h e More o f t e n some o f e n d o t h e l i a l l e u c o c y t e s f u s e t o form f o r e i g n b o d y g i a n t - cells. S o m e t i m e s t h e two p r o c e s s e s o f r e g e n e r a t i o n and o f r e m o v a l o f t h e n e c r o t i c m u s c l e - t i s s u e o f t h e same m u s c l e - f i b e r o v e r l a p and r e n d e r the p i c t u r e d i f f i c u l t to in te r p r e t" . -170- A c c o r d i n g t o M a l l o r y , m y o - r e g e n e r a . t i o n was a p p a r e n t l y p o s s i b l e and m u l t i n u c l e a t e d g i a n t c e l l s did e x i s t . a g r e e v e r y w e l l w i t h our f i n d i n g s . These t wo p o i n t s Ho we v e r , h i s observation on t h e r e m o v a l o f d e a d m u s c l e t i s s u e by p o l y m o r p h o n u c l e a r le u c o c y te s or e n d o t h e l i a l l e u c o c y te s , multinucleated g ia n t-c e lls ouite contrary and t h e f o r m a t i o n o f from e n d o t h e l i a l l e u c o c y t e s was t o o u r f i n d i n g s and wa s v e r y m i s l e a d i n g . rn r* I n 1PP6, Forbus f -O i n v e s t i g a t e d t h e d e g e n e r a t i o n and r e ­ g e n e r a tio n of t h e r e c t u s abdominis in pneumonia. He p o i n t e d o u t t h a t f o l l o w i n g d e g e n e r a t i o n o f t h e m u s c l e ( i e . h v s i itip d e g e n e r a t i o n ) , r e g e n e r a t i v e changes o c c u r r e d which l e d to the t o t a l r e s t o r a t i o n of the a f fe c te d muscle. generative p r o c e s s was d e s c r i b e d i n d e t a i l , o f w h i c h was a s f o l l o w s : "The h y a l i n e i s removed t h r o u g h t h e a c t i v i t y This r e ­ the e s s e n t i a l contractile substance of mononuclear wandering p h a g o c y t i c c e l l s which a r e o f e x t r a m u s c u l a r o r i g i n . The - m u s c l e - n u c l e i " o f —the;- old., fiber*' p r o l i f e r a t e -.and, p r o d u c e ""new muscle c e l l s , t h e i r c y t o p l a s m b e i n g d e r i v e d , from t h e e a r c o ­ plasm of th e o l d p a r t i a l l y muscle c e l l s , t h e new f i b e r preserved f i b e r . develops, From t h o s e e i t h e r from g r o w t h o f t h e i n d i v i d u a l c e l l o r f r om f u s i o n o f s e v e r a l c e l l s " . The f i n d i n g s i n w h i t e - m u s c l e d i s e a s e a g r e e i n most r e s p e c t s w i t h t h e work o f F o r c e s except , f o r t h e o r i g i n o f t h e p h a g o c y t i c cells found, i n t h e p r o c e s s o f m y o - r e g e n e r s t i o n and. t h e f u s i o n of s e v e r a l c e l l s findings, the phagocytic t o f or m new f i b e r . cells A c co r di ng to our (the muscle g i a n t c e l l s ) are o f m u s c u l a r o r i g i n and F o r b u s 1 f u s e d - c e l l s a r e i n r e a l i t y . -1 7 1 - m u l t i n u c l e a t e d muscle g i a n t c e l l s . I n t h e same y e a r (1936). Forbus ' c o n d u c t e d an e x p e r i ­ m e n t a l s t u d y on m y o d e g e n e r a t i o n and my o r e g e n e r a t i o n u s i n g vital stains. As a r e s u l t , and. s t a t e d t h a t he c o n f i r m e d h i s p r e v i o u s work "the p h a g o c y t i c c e l l s found w ith in the p e r s i s t e n t sar col emma. , w h i c h t o g e t h e r w i t h t h e m u s c l e c e l l s d e r i v e d from t h e m u s c l e n u c l e i o f V. ' aldeyer, form t h e "Muskelzellenschlauche are wandering c e l l s of e x tr a -m u s c u la r and h a v e no c o n n e c t i o n w i t h t h e m u s c l e c e l l s " , mentioned t h a t the "muscle c e l l s origin a l t h o u g h he as w e l l as p h a g o c y t i c c e l l s of " M u s k e l z e l l e n s c h l a u c h e " a r e c a p a b l e o f o e i n g s t a i n e d by i n t r a v e n o u s i n j e c t i o n of v i t a l d y e s during th e ir development, alone i s i n s u f f i c i e n t for muscle o r ig in (carmine o f tr y p a n blue) and hence such v i t a l staining d i f f e r e n t i a t i n g between c e l l s of and c e l l s o f e x t r a m u s c u l a r o r i g i n " . l y , Forbus d id n o t u s e M a l l o r y ' s a n i l i n blue s t a i n Unfortunate i n studying: t h e „..pr,eserved tissues,"' n t h e r v i s e . J i e . , . . . would have .realhzedl t h a t th e muscle g i a n t cells end t h e r e g e n e r a t i n g m u s c l e c e l l s w o u l d h a v e e x h i b i t e d t h e same s t a i n i n g affinity nuclei woul d a p p e a r e x a c t l y the of t h e s e same. two n e w l y - f o r m e d c e l l s T h i s woul d h a v e i n d i c a t e d c l e a r l y and some the muscular but n ot e x t r a - m u s c u l a r o r i g i n of th e muscle g i a n t c e l l s , x? Hay t h o r n ' ” , i n 1 9 3 8 , p u b l i s h e d an e x t e n s i v e r evi ew/ on the subject of "multinucleated giant c e lls " . t h e t e r m "Muscl e G i a n t C e l l s " they e x i s t e d . He m e n t i o n e d but h e s i t a t e d t o b e l i e v e t h a t He was of t h e o p i n i o n t h a t "while muscle r e p a i r c l u b s may r e s e m b l e f o r e i g n oody g i a n t c e l l s , l it is * -172- dou'otful i f th e y can ta k e capacity other them". f o r m a t i o n i n any body w h i c h a t t r a c t s he a g r e e d w i t h M a l l o r y considered the s o -c a lle d "foreign g ian t and F o r b u s and cells" i n myo- as of e x tr a -m u s c u la r o r i g i n . In 1931, r e s u l t s on t h e the in t h e i r th a t that of a foreign In f a c t , regeneration part 33 G o e t t s c l i and P a p p e n h e i m e r ' " r e p o r t e d t h e i r study of n u t r i t i o n a l muscular dystrophy in g u i n e a p i g and r a b o i t . They w e r e a b l e t o f i n d t h e seme p r o c e s s e s o f m y o d e g e n e r a t i o n f o l l o w e d by m y o - r e g e n e r a t i o n out agr eeo. e n t i r e l y w i t h F o r b u s i n r e s p e c t t o t h e o r i g i n o f the so -c a lle d invading "phagocytic h i s t i o c y t e s " . found l a r g e r n u l t i n u c l e a t e d plasm atic masses, l y i n g ag ainst the n e c r o t i c r e m a i n s o f t h e muscle s u b s t a n c e . i n g to our i n t e r p r e t a t i o n , In f a c t , accord­ the large rnultinucleated plasmatic m a s s e s e r e n o t h i n g more t h a n m u s c l e g i a n t so-called They a l s o "phagocytic h is tio c y te s " c e l l s and t h e a r e mo s t l i k e l y the developing muscle g i a n t c e l l s . The f o l l o w i n g y e a r (1932 a, b) , F i s h b a c k a n d F i s h b a c k 24,25 made an e x p e r i m e n t a l s t u d y on m u s c l e d e g e n e r a t i o n by u s i n g d i f f e r e n t t y p e s o f trauma.. infiltration They f o u n d t h a t a m o d e r a t e d i f f u s e o f p o l y m o r p h o n u c l e a r l e u c o c y t e s e nd l y m p h o c y t e s was i n d u c e d w i t h i n 24 h o u r s t i o n began t o fade a t 72 h o u r s . t h e r e wer e no i n f l a m m a t o r y after injury, phagocytic after injury cells le f t. end. o f f i v e days Seventy-two hours c e l l s containing debris appeared, and a t t h e end. o f f i v e d a y s , liferation At t h e bu t such i n f i l t r a ­ marked e a r l y muscle c e l l p r o­ o c c u r r e d around t h e margin of p a t c h e s of t h e f i b e r - 1 7 vi­ de g e n e r a t i o n . T h e r e wer e n u m e r o u s i r r e g u l a r with f i b r i l l a r e x t e n s i o n s , and s y n c y t i a l s p r o u t s w i t h m ultiple n u c le i. On t h e 1 8 t h and S l s t s p ro u ts " with m u ltip le n u c l e i , explanation, are (1934), wo r k e d on t h e p r o b l e m , " N u t r i t i o n a l myopathy i n d u c k l i n g s " , skimmed, m i l k p o w d e r , c a s e i n , end paper p u l p . w e r e f ound i n t h e generation. according to our P a o p e n h e i m e r and Go e t t - s c h The my op a t hy w a s i n d u c e d b y a s p e c i a l d i e t salts, The s o - c a l l e d pro bably t h e muscle g i a n t c e l l s . Two y e a r s l a t e r yeast, cells d a y s a few a r e a s of a l m o s t n o r m a l s i z e d new f i b e r s w e r e f o u n d . "syncytial single corn-starcn, c o n s i s t i n g of land, coo l i v e r o i l , The p a t h o l o g i c a l c h a n g e s s k e l e t a l m u s c l e s a s h y a l i n e or waxy de­ I n t h o s e c a s e s which s u r v i v e d l o n g e r , an e x t r e m e c e l l u l a r r e s p o n s e i n which m y o b la s ts , and l e u c o c y t e s o f d i f f e r e n t t y p e s t o o k p i e c e . t h e r e was histiocytes, Occasionally, b a s o p h i l i c r e g e n e r a t i n g m yocytes were p r e s e n t . • , 5 .4 .......•• ... Madsen, e t a.i ...... , ' in~‘ 1 9 3 5 , p u b l i s h e d " “wobk "brf " ' N u t r i t i o n a l ' m y o d e g e n e r a t i o n o f h e r b i v o r e , f e d n o r m a l and s y n t h e t i c r a t i o n s " . A m y o - d e g e n e r a t i o n was f o u n d i n t h e l e s i o n s and an a c t i v e ; n y o p h a g o c y t o s i s wa s o b s e r v e d , t o occur* s h o r t l y a f t e r They d i d n o t m e n t i o n e d , 10r however, the type o f c e l l s injury. responsible my 0 p h 0 g o c y t o s i s . In 1943, Boyd1,5 d i s c u s s e d g i a n t c e l l s and. s t a t e d "when the i n d i v i d u a l macrophages a r e u n a b le t o d e a l w ith p a r t i c l e s t o be removed, t h e y f u s e t o g e t h e r t o form m u l t i n u c l e a t e d plant c e l l s . — -Such a foreign cody g i a n t cell is a s y n c y t i u m c o n t a i n i n g a l a r g e number o f n u c l e i . a cytoplasm; In t h i s it form, the s e e ms t o h a v e g r e a t e r cells act singly". p h a g o c y t i c power t h a n when The w r i t e r a g r e e s w i t h B o y d ’s in te r p r e ta tio n regarding the function partly to the form ation of g i a n t c e l l s , i d e a as t o the o r i g i n of muscle g i a n t mentioned t h a t "some g i a n t d i v i s i o n of the nucleus" th e muscle g i a n t that of giant c e l l s cells. c e l l s are wh i c h i s but not with h is cells. Boyd a l s o f o r m e d by a m i t o t i c ap p a re n tly not Ag a i n i n r i s "H esling i n the muscle and found in b o o k , Boyd s t a t e d d e p e n d s on t h e k i n d s o f m u s c l e . P l a i n m u s c l e end h e a r t m u s c l e f i b e r s do n o t r e g e n e r a t e ; u n io n of t h e d i v i d e d p a r t s is by s c a r tissue. muscle has g r e a t e r r e p a r a t i v e power. g e n e r a t i o n d e p e n d s or. t h e lemma p r o l i f e r a t e the n u c l e i of the to the On ""the ot her * ■h a n d y f i b e r s have been d e s t r o y e d , r e m o v e d by m o n o n u c l e a r p h a g o c y t e s , the d e b ris i s w h i c h may f orm g i a n t and t h e g a p i s c l o s e d by f i b r o u s w r ite r agrees sarco- p u t s ou t b a n d s which b r i d g e th e gap "and' e v e n t u a l l y bebome ""'"striale"ti. cells, I n an i n c i s e d , and f or m r n u l t i n u c l e a t e d s y n c y t i a l m a s s e s w h ile the s a r c o u s su b stan ce when t h e m u s c l e The e x t e n t o f r e ­ type of i n j u r y . wound v; i t h no l o s s o f s u b s t a n c e , Striated tis s u e s ”. The i n c e r t a i n r e s p e c t s w i t h Boyd's s t a t e m e n t as p r o c e s s e s i n v o l v e d in myo-regener-atior. b ut does not agree with h i s i d e a of m y o p h a g o c y t o s is phagocytes nor to the o r i g i n of t h i s by m o n o n u c l e a r p a r t i c u l a r g r o u p of r i a n t c e l l s from mono nuclear p h a g o c y t e s . " m u l t in u c l e a t e d s y n c y t i a l mass" should of the m uscular g i a n t c e l l s . In f a c t , Boyd's be r e g a r d e d a s one -1 7 5 - I n t h e same y e a r ( 1 9 4 3 ) , r>8 Forbus , in dealing; with Asc'noff c e l l s , stated: curious single and. r n u l t i n u c l e a t e d g i a n t characteristic of the t y p i c a l "The n a t u r e j e c t of l o n g d i s c u s s i o n . and t h e o r i g i n o f t h e c e l l s w n i c h are s o A s c h o f f b o d y h a s been a s u b ­ These c e l l s have been d e s c r i b e d very c a re fu lly b y a number o f w o r k e r s . A s c h o f f and he thought i t what he c a l l e d the a d v e n t i t i a l c e lls most l i k e l y The e a r l i e s t was t h a t t h e y a r i s e from of the b lo o d v e s s e l s . G eip e l e x p r e s s e d t h e o p i n i o n t h a t t h e y a r e p r o b a b l y Later, 6 .e r i v e d xruii) orcliii&ry conr i 6 c1 1v c 1 1 s s u 6 C e l l s . early d escriptio ns, opinion S i n e s *fclis as t o t h e n a t u r e o f t h e s e c e l l s have v a r i e d , a s i n d i c a t e d by t h e many n a me s g i v e n t o t hem, for fibroblasts, example, th e lia l cells, forth. epithelioid The r e c e n t supravital, connective cells, tissue cells, muscle c e l l s , and so s t u d i e s by Me Even, i n which modern, c y t o l o g i e s ! t e c h n iq u e s were used, . t hat-“~the ' 'As-eho -ff - c e l l s most " L i k e l y seem t o show a r l-ee~~from u n d i f f e r e n t i n t ­ ed m e s e n c h y m a l e l e m e n t s o f l o o s e c o n n e c t i v e t i s s u e . with these o b se r v a tio n s, development of th e a part, and y e t it woul d seem mo s t l i k e l y p e c u l i a r Aschoff c e l l s a rather peculiar- p e r t , a c tio n of the connective t i s s u e . " been a b l e t o a s c e r t a i n t h e s o - c a l l e d " Aschoff c e l l s " . muscle d is e a s e endo­ t h a t the c o n s t i t u t e s simply of the h e a l i n g r e ­ Apparently, exact natu re In lin e no one h a s and o r i g i n o f th e R e f e r r i n g ; t o t h e s t u d y on w h i t e o f new-born l a m b s , it was o b s e r v e d t h a t t h e m u s c l e g i a n t c e l l s i n t h e h e a r t wer e s m a l l e r t h a n t h o s e found in the s k e l e t a l m uscl e but possessed, a l l t h e -1 7 6 characteristics the w r i te r of the s o - c a l l e d t o b e l i e v e that, "Aschoff c e l l s " . the s o - c a l l e d "Aschoff c e l l s " p r o b a b l y n o t h i n g more t h a n c a r d i a c m u s c l e g i a n t the This l e a d s are c e l l s and "Aschoff b o d i e s " i n myocardium a r e only m ass es o f t i s s u e c o n s i s t i n g of r e g e n e r a t i n g c a r d ia c muscle c e l l s and c a r d i a c m u s c l e g i a n t c e l l s t o g e t h e r w i t h a few f i b r o b l a s t s , occasion­ a l plasma c e l l s , leucocytes. lymphocytes, and p o l y m o r p h o n u c l e a r F u rth e r i n v e s t i g a t i o n i s needed in o r d e r to c l e a r up t h i s situation. In heart t he Same y e a r (syphilitic present. stated 5 h a v i n g t h e same i r r e g u l a r they *7o m e n t i o n e d gumma o f and s t r e s s e d t h e e x i s t e n c e "Here end t h e r e , But, giant c e l l s i n s. gumma t h a n t h e y a r e i n cytoplasm, Ogilvie m yocarditis) of g i a n t c e l l s , is (1343), are, as a r u l e , a tuberculoma. l e s s n u me r o u s Further, s h a p e and g r a n u l a r , are g en erally a giant cell while acidophilic s m a l l e r and c o n t a i n few er hue l e i '" 1 'Under'"' such" cordl t± one g - t h e "cardi-ac* m u s c le - g i a n t c e l l s - . might also e x i s t . In the stated: F u r t h e r i n v e s t i g a t i o n might, r e v e a l t h i s d i s c u s s io n of foreign-Dody g i a n t c e l l s , fact. Ogilvie "They a r e known a s f o r e i g n - b o d y g i a n t c e l l s , because they ere f r e q u e n t l y found i n r e l a t i o n t o fo reig n b odies s u c h a s c a t - g u t o r v e g e t a b l e - m a t t e r embedded i n t h e t i s s u e s . They a l s o o c c u r 1 i n t h e n e i g h b o r h o o d o f p a t h o l o g i c a l d e p o s i t s which are d i f f i c u l t , secretions, fat to a b s o r b such as u r a t e s , and k e r a t i n , and o t h e r inspissated, features in tis s u e s c h r o n i c a l l y i n f l a m e d oy b a c t e r i a l i n f e c t i o n ............... Some of t hem c o n t a i n c e 1 1 - d e b r i s or f a t and i t is likely that their -1 7 7 - main c a p a c i t y i s , f r om t h i s t h e i r clear. indeed, that, o f p h a g o c y t o s i s , function is P r o b a b l y mo s t a r e of f ib r o b l a s ts . And i t obscure. Nor i s t h e i r derivatives d i v i s i o n of th e d i v i s i o n of the c y to p lasm , fusion is possibly the s o - c a l l e d though sometimes Apparently, evidence to support h i s statem ent f u n c t i o n and mode o f f o r m a t i o n o f 11f o r e i g n - b o d y g i a n t c e l l s " . e v i d e n c e o b t a i n e d f r om o u r white-muscle the method". concrete regarding the o rig in , others w o u l d a p p e a r t h a t t h e commones t nucleus without 0 fell v i e had l i t t l e origin of h i s t i o c y t e s , node o f f o r m a t i o n i s r e p e a t e d a m i t o t i c of c e l l s but a p a r t Perhaps the f i n d i n g the muscle g i a n t c e l l s in d i s e a s e o f y o u n g l a m b s may s e r v e a s a b a s i s f o r f u r t h e r i n v e s t i g a t i o n of o t h e r kinds of g ia n t c e l l s . In a b r i e f d is c u s s io n of the s u b je c t rnyo-regeneration" it seerns Q u i t e as p r e s e n t e d i n t h e possible th a t on " m y o d e g e n e r a t i o n foregoing paragraphs, t h e p a t h o l o g i c a l p h e n o m e n a ob­ s e r v e d i n t h e c a s e s of w h i t e muscle d i s e a s e of new-born l a m b s may s e r v e a s a. g u i d i n g p r i n c i p l e number of o t h e r diseased conditions disturbances, rheumatic etc. tion s uch as t u b e r c u l o s i s , fever, syphilitic i n the study of a involving muscular pneumonia, m yocarditis, typhoid fever, scarlet fever, and In t h e s e m u s c u l a r d i s t u r b a n c e s i n v o l v i n g m yod eg en er a­ and r n y o - r e g e n e r a t i o n , would follow i n one way o r the tiss u e re a c tio n another the to i n j u r y same p a t h o l o g i c a l p a t t e r n as d e s c r i b e d i n c a s e s o f w h i t e - m u s c l e d i s e a s e . fancy term " M u s k e l z e l l e n s c h i a u c h e " o f Yval deyer i s a ma s s o f r e g e n e r a t i n g s k e l e t a l m u s c l e The in r e a l i t y c e l l s and s k e l e t a l -1 7 8 - m u s c l e g i a n t c e l l s t o g e t h e r w i t h a few f i b r o b l a s t s . s o - c a l l e d " A s c h o f f body" i n the myocardium i s most l i k e l y a group of r e g e n e r a t i n g c a r d i a c muscle c e l l s , muscle g i a n t - c e l l s cells, and p o l y m o r p h o n u c l e a r l e u c o c y t e s . The " A n i t s c h k o w figure, w hile the p r o b a b l y n o t h i n g more t h a n a c a r d i a c m u s c l e F u r th e r m o r e , th e terms such as " r e p a i r a masses", u w v l i v j UJ.O.L O o r» « * * >O II1U.U D U v ^ f "Aschoff c e l l " giant cell. clubs of muscle", ^ 'r m l t i 1 11 w i n n h l o r+C . ^ J.V-U<.'U u " s y n c y t i a l s p ro u ts with m u l t i p l e n u c l e i " , s y n c y t i u m w i t h a l a r g e nu mo e r o f n u c l e i " , c e l l s in muscle" plasma be a r e g e n e r a t i n g c a r d i a c m u s c l e c e l l w i t h an a c t i v e m i t o t i c /| — , , o 4- ^ ti l U. _L cardiac and o c c a s i o n a l l y a f ew l y m p h o c y t e s , myocyte" i s c o n s i d e r e d t o is The are a c tu a lly *1 n Pi n n + i n ^ m tMjiJit.' w i . v "Cytoplasmic and " r n u l t i n u c l e a t e d d e s i g n a t i o n s for muscle g i a n t cells. In a d d i t i o n , disburbances, the the w r i t e r f e e l s that fundamental p a th o lo g ic a l processes in - - v o I v e d -c a n b e ■b r i e f l y ' ' n - t a t e d a s f o l l o w s r (l). If i n any m u s c u l a r .... . --- a s t r o n g e t i o l o g i c a l a g e n t i s met and t h e i n j u r y s e v e r e , +he t i s s u e r e a c t i o n woul d f o l l o w an i n f l a m m a t o r y process. The a f f e c t e d m u s c l e f i b e r s w o u l d u n d e r g o v a r i o u s p ha s e' s o f n e c r o s i s and an a c t i v e i n f i l t r a t i o n o f p o l y m o r p h o ­ n u c l e a r l e u c o c y t e s end o t h e r w a n d e r i n g c e l l s later on l y m p h o c y t e s o r p l a s m a c e l l s ) ( m a c r o p h a g e s end woul d be i n d u c e d and a u s c e s s a t i o n may r e s u l t . I f the animal s u r v i v e s or l i v e s longer, repair p l a c e and t h e l e s i o n s wo u l d be could take f i l l e d with s c a r t i s s u e . u n d e r such c o n d i t i o n s . No my o - r ege n e r a t i on i s In s n o r t , possible t h e who l e p r o c e s s may be is -1 7 9 - d e s i g n a t e d as " m y o - i n f l a m m a t i o n and s c a r - t i s s u e r e p a i r " . In a very r a r e white-muscle ( 2) this p r o c e s s was o b s e r v e d i n disease. I f t h e e t i o l o g i c s l a g e n t was m i l d or r o t and t h e damage typical instance, so s t r o n g t o t h e m u s c u l a r t i s s u e was n o t s e v e r e , the " m y o d e g e n e r a t i o n a n d my or e g e n e r a t i on" a s i l l u s t r a t e d i n t h e c a s e o f w h i t e —mu s e 1 e d i s e a s e w o u l d t a k e p l a c e . -1 3 0 - V. 1. Fifty-five Summary and c o n c l u s i o n c a s e s o f n e w - b o r n lain'os a f f e c t e d w i t h a v a r i e t y o f d i s e a s e s were i n c l u d e d i n t h i s i n v e s t i g a t i o n a n d t n e p r o cl em was s t u d i e d by means o f h e m a t o l o g i c a l , ua.cteriological, p. a n a p a t h o l o g i c a l met hods, , From t h e h e m a t o l o g i c a l a s p e c t , both c e l l u l a r determina­ t i o n s and c h e m i c a l a n a l y s e s o f t h e in d e t a i l and d i s c u s s e d 3. A sim ilar (controls) b l o o d s t u d y on was a l s o i n c l u d e d . The b a c t e r i o l o g i c a l s t u d i e s i n c l u d e d t h e i s o l a t i o n o f 4-1 c u l t u r e s of aero b es and 7 a n a e r o b e s from v a r i o u s c a s e s . Ni ne g e n e r a o f b a c t e r i a wer e i d e n t i f i e d , Staphylococcus, Diplococcus, N e is se ria , Bacterium, 4. studied f u l l y in c o n n e c tio n w ith the various individual cases. n o r m a l s h e e p and l a m e s b l o o d wer e Pasteurella, namely, Escherichia, Coryneoacterium, Actinomyces, Clostridium. T\o o I t u r e s we r e u n d e t e r m i n e d . Ag a r e s u l t o f p a t n o l o g i c a l end B a c t e r i o l o g i c a l 15 d i f f e r e n t ty p es of d i s e a s e s were d i a g n o s e d , wnite-muscle disease, staphylococcic infection, docking i n f e c t i o n , pneumonia, pesteurellosis, peritonitis, dietary enteritis, deficiency, determ ined group. and studies, including: i n f e c t io n , navel c a s t r a t i o n wo u n d , b r o n c h o ­ e n t e r - o t o x e . mi e , m e n i n g i t i s , gastric ulceration co ngenital anomalies, Most o f t h e s e and p e r f o r a t i o n , and an un­ d i s e a s e s were s t u d i e d more o r l e s s i n d e t a i l and a nu mbe r o f c o n d i t i o n s wer e re p o rte d f o r the f i r s t time. -1 3 1 - The f i n d i n g o f m u s c l e g i a n t c e l l s ( s k e l e t a l and c a r d i a c ) i n t h e c a s e s o f w h i t e - m u s c l e d i s e a s e end t h e i r significance i n r n y o - r e g e n e r a t i o n a r e c o n s i d e r e d new t o m e d i c a l s c i e n c e and o f v i t a l i m p o r t a n c e i n e x p l a i n i n g the p a t h o l o g i c a l phenomena i n v o l v e d . The s p e c i f i c of t h e i r f u n c t i o n of muscle g i a n t c e l l s f o r m a t i o n were A b r i e f and c o n c i s e a n d t h e modes fully discussed, s t a t e m e n t wss g i v e n c o n c e r n i n g t h e pathological processes involved in muscular d i s t u r b a n c e s . The p r o c e s s e s i n v o l v e d a r e d e s i g n a t e d and s c p r - t i s s u e r e p a i r " for tissu e as " m y o - i n f l a m m e t i o n r e a c ti o n to a severe injury and " m y o - d e g e n e r a t i o n and ; n y o - r e g e n e r a t i o n " f o r tissue r e a c t i o n toward a mild i n j u r y . The i i i s t o p a t n o l o g y o f wni t e - m u s o l e d i s e a s e i n l a m b s was s t u d i e d ir; d e t a i l , and t h e p a t h o l o g i c a l phenomena ob­ served were s u g g e s t e d as a guide f o r the s tu d y of a ...number o f human... . d i s e a s e s ...with . m u s c u l a r i n v o l v e m e n t s u c h as, tuberculosis, fever, pneumonia, typhoid fever, rheumatic s y p h ilitic m yocorditis, s c a rle t fever, and e t c . The c a r d i a c m u s c l e was o b s e r v e d t o p o s s e s s t h e c a p a c i t y for regeneration, and t h i s i s a l s o c o n s i d e r e d r.ew t o medical s c ie n c e . The n a t u r e myocyt e" and o r i g i n o f t h e s o - c a l l e d " A n i t s c h k o w and " A s c h o f f c e l l " w e r e f u l l y e v i d e n c e wa s g i v e n i n t h e myoc a r d i u n . o e e r i n g on t h e d i s c u s s e d and position of these c e lls -1 8 ? — 11. The f a n c y muscle", and p e c u l i a r terms such as " r e p a i r c l u b s of "rnultinucleated s y n c y tia l masses", rnultinucleated plasm atic masses", with m u l t i p l e n u c l e i " , "large "syncytial sprouts "cytoplasmic syncytium w ith a l a r g e n u mb e r o f n u c l e i " , and " m u l t i n u c l e a t e d , c e l l s i n muscle" were e x p l a i n e d . 1?. The n a t u r e end t h e o r i g i n o f t h e s o - c a l l e d "Muskel- z e l l e n s c h l a u c h e " o f W a l d e y e r was d i s c u s s e d i n d e t a i l . 13. The n a t u r e and o r i g i n of the so-called " A s c h o f f oody" was d i s c u s s e d and s u g g e s t i o n s c o n c e r n i n g f u r t h e r i n ­ v e s t i g a t i o n s wer e m e n t i o n e d . 14. A new t e c h n i c o f o p e n i n g t h e c r a n ia l cavity fo r brain e x a m i n a t i o n was d e s c r i b e d . 15. The n a t u r e o f t h e v a r i o u s d i s e a s e s o f n e w - b o r n l ambs were s t r e s s e d , and s u g g e s t i o n s wer e made f o r the c o n t r o l o f some o f t h e more i m p o r t a n t c o n d i t i o n s . -1 8 3 VI. Bibliography 1. A l l c r o f t , VJ. M. 1 9 41 . - O b s e r v a t i o n on t h e h e m o g l o b i n l e v e l o f cows and sheep. J o u r . A g r i c . S c i . 31: 320-335. 2. Ame r i c a n B a c t e r i o l o g i s t s ( S o c i e t y o f ) . 1936-44. Manual o f m e t h o d s f o r p u r e c u l t u r e s t u d y o f b a c t e r i a (Up t o d a t e c u r r e n t r e v i s i o n s ) . B i o t e c h P u b l i c a t i o n s , Box 2 9 9 , G e n e v a , N. Y. 3. Anderson, 1937. - 4. B a k e r , E. T. 1929. S h e e p d i s e a s e ? , 2nd e d . , Alexander Eger, Chicago. 5. A, X. The c a l c i u m and p h o s p h o r u s c o n t e n t o f t h e se r um o f l a m b s a f f e c t e d w i t h " s t i f f l amb disease". P e n n s y lv a n ia A g ric. 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Ani m. 3 c i . 3: 453. 113. W i l s o n , M. 6 . , and L u b s c h e z , R. 194?. Prognosis for c h ild re n with co ng enital a n o m a l i e s o f t h e h e a r t and c e n t r a l v e s s e l s . L ife expectancy in p a t e n t ductus a r t e r i o s u s , J o u r ,_ P e a , Pi : . 9 3 - 3 0 . 114. Wyoming: 1936-37. J . P . , McCay, C. M. , M o r r i s o n , F. B . , and P. , I b i d . flew i o r K ^ C o r n e l l ; A g r i c . «j’ ■*•* 'v.>r.7-'v/v'Sii#C‘ «• " fe.y»*isg" i •' • -i. !'•■*? .l*£*Lag£ a ^ M S l Fig* • Case 7 372. Lung show ing A ctinom yces necrophorus a b s c e s s . ------- ------(H & l ) , x 116. F ig . 33 . Case 7 3 9 4 . Smear from carpal, j o in t shew ing p h a g o c y to sis of s t a p h y lo c o c c i. (W right*s s t a i n ) , x 1640* P l a t o 20 - S|ys^0Eteif ^**j? ppssfttspi »* t # * # F ig . 34. Casa 7 3 94 . S u p p u ra tiv e m y o c a r d it is . (H ft E ) , X 1 0 6 . F ig . 3 5 . Caae ? ? 9 4 . H eart shew ing ch ro n ic su p p u r a tiv e l e s i o n . (H & E ), X 1 0 6 . ~ Plate 21- ;s X g y ^ . y ^ £*¥<- *% & % & & ?<*:?' F i g . 36. Casa 7362. S p in a l cord showing a b s c e s s a t io n . F ig . 37. Case 73 6 2 . Cross s e c t io n of s p in a l cord showing a b s o e s s a t io n . (H & E ), X 6 . - p la t® 22 - m %r ’V ^w. ■fit Fig* 38* Case 73 6 5 , Cross s e c t io n of s p in a l cord showing a b s c e s s a tio n and hemorrhage. (Gram-’STelgert) e X 6 . Plat® 22a F i g . 39. Case 7 3 6 5 . S p in a l cord show ing l e s i o n c o n ta in in g A ctinom yces nscrophoruB and a d ip h th e r o id . (oram -W eigort) t x*~ 1 4 40. F ig . 4 0 . Case 7 3 0 8 . L iv er show ing f a t t y d e g e n e r a tio n and n e c r o s is around c e n t r a l v e i n . (H <5b E ) , X 5 9 0 . - P i n t s 23 Fig® 41® Cass 7 3 2 9 , Lung show ing i n t e r s t i t i a l bronchopneum onia, Wota t h e t u b e r c l e - l i k e ly m p h o cy tic i n f i l t r a t i o n . (H & E ) , X 9 7 . F i g . 4 2 . Case 7 3 2 9 . H igh power o f t h e sam e. (H & E ) , X 600 - r l a t e 24 - F ig . 4-3. Case 7 35 3 . Lung show ing hem orrhagic bronchopneumonia. (H & E ) » X 160. F ig . 4 4 . Case 7 4 1 5 . B rain showing p e r iv a s c u la r c e l l i n f i l t r a t i o n . (H & E ) , X 6 3 0 . - P la t e 25 - F ig . 4 5 . Case 7 3 3 4 . S p leen show ing s e r o s a l c o n g e s tio n and hemorrhage in t o c a p s u le . (H & E ) t X 116. F ig . 4 6 . Case 7 3 9 9 . I n t e s t i n e showing hemorrhage due t o e n te ro to x er a ia . - P la t a 26 •* S p leen show ing s e r o s a l c o n g e s tio n and hemorrhage in t o c a p s u le . (H & E ) , X 1 1 6 . F ig . 4 6 . Case 7 3 9 9 . I n t e s t i n e show ing hemorrhage due t o en tero to x era ia . - P l a t a 26 - mmm F ig . 4 7 . e a s e 7 3 9 9 . S e c tio n o f i n t e s t i n e show ing marked subm ucosal hem orrhage. (H & E ) „ X 8 0 . P ig . 4 8 . Case 7 4 0 0 . B rain show ing m e n in g it is . (H & E ) , X 6 3 0 . P l a t e 27 • . -a. J :< M £. uMWf'k I n t e s t in e showing s e r o s a l involvem ent due t c p e r ito n itis . 50. Case 7 4 0 6 . L iver showing n e c r o s is near c a p s u le , acu te p e r i t o n i t i s . (H & E) t X 116. A cae of - P l a t o 28 - 4 F ig . 51. Case 7336. I n t e s t in e showing hemorrhagic e n t e r i t i s . (H & e ) „ 60. F ig . 52. Case 7344. Stomaoh showing u lc e r a t io n . (H & l ) 8 X 1 5 . - F l a t e 29 - F ig . 53. Case 6598. R eg e n e ra tin g c a r d ia c m u scle f ib e r s w ith v a r io u s s ta g e s of m i t o s i s , c e l l o f t h i s kind has been c a l l e d "A nitschkow myocyte'*. (H & E) , X 9 0 0 . F ig . 54. Case 6 5 9 8 . Heart show ing c a r d ia c m uscle g i a n t - c e l l . N ote th e c e l l w ith two or t h r e e n u c l e o l i in each n u c le u s . C e ll o f t h i s k in d has been c a lle d " A sch off c e l l " . (H & E ) , X 9 0 0 . - Flat© 30