R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d i c i n a T r o p i c a l 2 6 ( l ) : l - 4 , j a n - m a r , 1 9 9 3
ARTIGOS
TETANUS AS A CAUSE OF ACUTE RENAL FAILURE:
POSSIBLE ROLE OF RHABDOMYOLYSIS
R e i n a l d o M a r ti n e l l i , C á c ia M . M a to s a n d H e o n i r R o c h a
T o s t u d y t h e f r e q u e n c y a n d e x a m in e l h e r o l e o f r h a b d o m y o l y s i s in t h e a c u t e r e n a l f a i l u r e in t e t a n u s 1 8 p a t i e n t s w i th t h e d i a g n o s i s o f g e n e r a l i z e d te t a n u s c o n s e c u t i v e l y a d m i t t e d t o th e i n f e c t i o u s d i s e a s e h o s p i t a l w e r e e v a lu a te d . O f t h e s e 1 4 w e r e m a le a n d 4 f e m a l e w i th m e a n a g e o f 3 1 . 8 ±_ 2 . 0 y e a r s . E x c e p t f o r m i l d p r o t e i n u r i a r e c o r d e d in 9 p a t i e n t s , l h e u r i n a l y s i s w e r e u n r e m a r k a b l e . S e r u m c r e a t i n i n e h i g h e r t h a n 1 . 4 m g / d l w a s r e c o r d e d in 3 9 % o f t h e p a t i e n t s , a b n o r m a l l e v e i s o f C P K in 8 7 , 5 % a n d s e r u m m y o g l o b i n g r e a t e r th a n 1 2 0 / i g / l in 3 9 % o f t h e p a t i e n t s . O l ig u r i a w a s d o c u m e n t e d in o n e p a t i e n t a n d n o n e r e q u i r e d d i a f y s i s t h e r a p y . N o c o r r e l a t i o n w a s f o u n d b e t w e e n r e n a l f a i l u r e a n d m y o g l o b i n a n d / o r C P K s e r u m le v e is . A c u t e r e n a l f a i l u r e in t e t a n u s w a s n o t i n fr e q u e n t; u s u a lf y i t w a s n o n - o l i g u r i c , m i l d a n d t r a n s i e n t a n d n o t r e l a t e d to th e s e v e r i t y o f l h e d i s e a s e o r t o s e r u m le v e i s o f m y o g l o b i n a n d / o r C P K .
K e y - w o r d s : T e t a n u s . R h a b d o m y o ly s is . M y o g lo b i n . A c u t e r e n a l f a i l u r e .
T e ta n u s is a d is e a s e c a u s e d b y te ta n o s p a sm in , a p o te n t to x in e la b o r a te d a t th e s ite o f in ju ry b y C.
te ta n i, a n a n a e ro b ic , s p o re -fo rm in g , g ra m -n e g a tiv e
r o d 21. A lth o u g h in fre q u e n t in th e w e ll-d e v e lo p e d c o u n trie s, te ta n u s is o f p a r tic u la r s ig n ific a n c e in th e th ird w o r ld 16.
T h e c lin ic a i fe a tu re s o f te ta n u s a r e p ro d u c e d b y th e n e u r o to x ic a c tiv ity o f te ta n o s p a sm in 9 21. T h e i n t e n s e m u s c u l a r w o r k r e s u l t i n g in rh a b d o m y o ly s is w ith re le a s e o f m y o g lo b in an d m u s c u la r e n z y m e s , th e p r o f u s e s w e a tin g , th e
o v e ra c tiv ity o f th e s y m p a th e tic n e r v o u s sy ste m an d th e m e ta b o lic d is tu rb a n c e s th a t ac co m p an y tetan u s m ay c a u s e im p a irm e n t o f th e re n al fu n c tio n . A cu te re n a l fa ilu r e h a s b ee n re p o rte d in fre q u e n tly in te ta n u s; in a la rg e s e rie s o f 1 00 c a ses it w a s n o t o b s e rv e d in a n y s in g le p a tie n t6, w h ile it w a s fo u n d in o n ly 2 o u t o f 103 c h ild re n in an 11 y e a rs re v ie w 22. In a s e le c te d g ro u p o f p a tie n ts , h o w e v e r, ac u te re n a l fa ilu re w a s fo u n d in 14% o f th e m 10. T h e p u r p o s e o f th e s tu d y w a s to d e te r m in e th e fre q u e n c y o f a c u te re n a l fa ilu re a n d to e x a m in e th e
D e p a r tm e n t o f M e d i c i n e , F e d e r a l U n iv e rs ity o f B a h ia M e d ic a i S c h o o l, S a lv a d o r B A B ra z il.
T h is s t u d y w a s s u p p o r t e d b y C o n s e l h o N a c i o n a l d e D e s e n v o lv im e n to C ie n tíf ic o e T e c n o ló g ic o - C N P q , B razil (G ra n t n ° ' 4 0 7 6 7 0 /8 5 C L ) .
A d d r e s s f o r c o r r e s p o n d e n c e : D r . R e in a ld o M a r tin e lli. F A C P / L a b o ra tó rio d e N e f r o lo g ia - 1 1 1 7 H o s p ita l U n iv e r s itá r io P ro f. E d g a rd S a n to s . R u a J o ã o d a s B o ta s s /n , C a n e la 4 0 1 1 0 - 1 6 0 S a lv a d o r, B A , B ra s il.
R e c e b id o p a r a p u b lic a ç ã o e m 1 9 /1 1 /9 2 .
ro le o f m y o ly s is a n d m y o g lo b in e m ia o n th e re n al fu n c tio n in a d u lt p a tie n ts w ith g e n e ra liz e d te ta n u s.
M A T E R IA L A N D M E T H O D S
E i g h t e e n p a t i e n t s w i t h t h e d i a g n o s i s o f
g en e ra lize d tetan u s c o n se cu tiv ely a d m itte d to H o sp ital C o u to M a ia (In fe c tio u s D is e a s e H o s p ita l in S alv ad o r- B ah ia -B ra zil) w e re p ro s p e c tiv e ly stucfied. A t th e tim e o f a d m is s io n a d e ta ile d m e d ic a i h is to ry w a s o b ta in e d , a n d a li p a tie n ts w e re e v a lu a te d b y p h y s ic a l e x a m in a tio n , u rin a ly s is , c o m p le te b lo o d c e ll c o u n t, d e te rm in a tio n s o f s e ru m le v e is o f e le c tro ly te s , u re a n itr o g e n , c r e a tin in e , c r e a tin e p h o s p h o k in a s e a n d m y o g lo b in . N o p a tie n t r e c e iv e d in tr a m u s c u la r in je c tio n s b e f o re th e in itia l la b o ra to ry e v a lu a tio n .
S eru m m y o g lo b in w a s m e a s u re d b y im m u n o c h e m ic a l m e th o d , u s in g a c o m m e r c i a l l y a v a i l a b l e k i t (B e h rin g w e rk e A G , M a r b u r g , G e rm a n y ); b y th is m e th o d , p o s itiv ity c o r r e s p o n d s to a m in im u m m y o g lo b in c o n c e n tra tio n o f 1 2 0 ^tg/1, a v a lu e 1.5 tim e s h ig h e r th an th e u p p e r lim it o f n o rm a l412. T h e d ia g n o s is a n d s e v e rity o f te ta n u s w e r e e s ta b lis h e d o n th e b a s is o f c lin ic a i m a n ife s ta tio n s . F o r th e p u rp o s e o f th e p re s e n t s tu d y , in c u b a tio n p e r io d w a s th e in te rv a l b e tw e e n w o u n d in g a n d th e f ír s t s y m p to m o f te ta n u s; a c u te re n a l fa ilu re w a s d e f in e d a s a ris e in s e ru m c r e a tin in e to le v e is h ig h e r th a n 1 ,4 m g /d l, n o t r e v e rs ib le b y c o r re c tio n o f v o lu m e s ta tu s o r an y o th e r e x tra -re n a l a b n o r m a litie s th a t c o u ld c a u s e p re - re n a l az o te m ia . A li p a tie n ts w e re e s s e n tia lly k e p t in
M a r t i n e l l i R , M a t o s C M , R o c h a H . T e t a n u s a s a c a u s e o f a c u t e r e n a l f a i l u r e : p o s s i b l e r o l e o f r h a b d o m y o l y s i s . R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d i c i n a T r o p i c a l 2 6 . 1 - 4 , j a n - m a r , 1 9 9 3 .
b e d re s t; p a re n te ra l flu id s a n d m e d ic a tio n s w e re g iv e n v ia in tra v e n o u s in fu s io n . T h e c o u rs e o f each p a tie n t w a s a n a ly s e d b y d a ily c lin ic a i e v a lu a tio n , re c o rd in g flu id b a la n c e , u rin e v o lu m e , c u r re n t
m e d ic a tio n s a n d fr e q u e n t la b o ra to ry e v a lu a tio n . S ta tis tic a l a n a ly s is w e r e d o n e u s in g F is h e r ’s ex a c t tes t. S ta tis tic a l s ig n ific a n c e w a s d e fin e d as p < 0 . 0 5 .
R E S U L T S
O f th e 18 p a tie n ts e n r o lle d in th is s tu d y 14 w e re m ales a n d 4 fe m a le s , w ith a m ea n a g e o f 3 1 .8 4 ^ 2 .0 y ea rs . T h e p a tie n ts w e re s tu d ie d d u rin g th e firs t
w e e k o f th e d is e a s e ; th e in c u b a tio n p e r io d v a rie d fro m 2 to 14 d a y s (m ea n : 9 .7 + 8 .4 d ay s) a n d th e in te rv a l b e tw e e n th e o n s e t o f s y m p to m a to lo g y a n d h o s p ita l a d m is s io n w a s 3 . 0 . + 1 .9 d a y s (1 to 5 d a y s ). A li p a tie n ts w e re in g e n e ra l g o o d h e a lth b e f o re th e ir te ta n u s a n d n o h is to ry o f a lc o h o l o r d ru g a b u s e , o r u sin g n ep h ro to x ic d ru g s c o u ld b e elicite d . A p h y si cal e x a m in a tio n s h o w e d a li p a tie n ts h a d re c o g n iz a b le w o u n d s , f r e q u e n tly in lo w e r lim b s . T h e te ta n u s w a s g e n e ra liz e d in a li p a tie n ts a n d g ra d e d a s m ild in 4 p a tie n ts , m o d e ra te in 9 a n d s e v e re in 5 (T a b le 1).
F e v e r , tris m u s , m u s c le s s p a s m s , o p is th o to n u s a n d m u s c le rig id ity w e re p r e s e n t in m o s t p a tie n ts , d u rin g th e h o s p ita liz a tio n ; d a ily u r in e o u tp u t less
th a n 4 0 0 m l w a s re c o rd e d in o n ly o n e p a tie n t. In th e la b o ra to ry e v a lu a tio n , e x c e p t f o r m ild p ro te in u r ia e x h ib ite d b y 9 (5 0 % ) p a tie n ts , th e u rin a ly s is w a s u n im p re s s iv e : n o p ig m e n te d o r re d b lo o d ce ll c a s ts w e re id e n tifie d in a n y p a tie n t. S e ru m c r e a tin in e c o n c e n tra tio n s h ig h e r th a n 1. 4 m g / d l w e re re c o rd e d in 7 (3 9 % ) p a tie n ts in a b s e n c e o f e x tra -re n a l a b n o rm a litie s th a t m a y h a v e c a u s e d p re - re n al az o te m ia. C re a tin o p h o s p h o k in a s e le v e is a b o v e 3 6 IU w e re fo u n d in 14 fr o m th e 16 ( 8 7 .5 % ) in w h o m i t w a s m e a s u r e d . S e r u m m y o g l o b i n c o n c e n tra tio n s g r e a te r th a n 1 2 0^tg /l w e r e d e te c te d
in 7 (3 9 % ) o u t o f 18 p a tie n ts . T h e c lin ic a i c o u rs e w a s c h a ra c te riz e d b y a c o m p le te r e c o v e r y . T h e m o rta lity o f th e g ro u p w a s 2 7 .8 % ; th e c a u s e s o f d e a th w e re u n re la te d to re n a l fa ilu re in a l i , a lth o u g h 3 o f th e p a tie n ts w ith a c u te re n a l f a ilu r e d ie d .
T h e c o r re la tio n b e tw e e n a c u te re n a l f a ilu re a n d m y o g lo b in e m ia , as s h o w n in T a b le 2 , w a s n o t s ig n ific a n t. A ls o , c o r r e la tio n b e tw e e n a c u te re n a l fa ilu re a n d s e ru m le v e is o f C P K o r s e v e rity o f te ta n u s c o u ld n o t b e e s ta b lis h e d .
T a b le 1 - T e ta n u s a s a c a u s e o f r e n a l f a i l u r e a n d r h a b d o m y o l y s i s : s o m e c l i n i c a i a n d l a b o r a t o r i a l d a ta .
N ° S e v e rity P ro te in u r ia C re a tin in e
(m g /d l)
C P K (IU )
M y o g lo b in e m ia
1 M ild + 0 .8 2 4 9 +
2 M ild N e g 0 .8 N e g
3 M ild * + 1 .4 2 6 N e g
4 M ild N e g 1 .4 1 6 6
+
5 M ild N e g 1 .8 16 N e g
6 M o d e ra te + + 0 .7 5 7 N e g
7 M o d e r a te + + 0 .8 109 +
8 M o d e ra te N e g 1 .0 171 +
9 M o d e ra te + 1 .2 2 0 2 N e g
10 M o d e ra te + 1 .4 109 N e g
11 M o d e ra te * N e g 1 .6 125 N e g
12 M o d e ra te N e g 1 .8 6 8 N e g
13 S e v e re * N e g 1 .0 8 1 9 +
14 S e v e r e + 1 .4 2 0 2 N e g
15 S e v e re * N e g 1 .5 6 2 8 +
16 S e v e r e + 1 .5 N e g
17 S e v e r e N e g 1 .8 16 N e g
18 S e v e re * + 3 .2 2 4 9 +
N o rm a l v a lu e s : c r e a tin in e = 0 .4 to 1 .4 m g /d l C P K = 0 to 3 6 IU
* = d e a th
M a r t i n e l l i R , M a t o s C M , R o c h a H . T e t a n u s a s a c a u s e o f a c u t e r e n a l f a i l u r e : p o s s i b l e r o l e o f r h a b d o m y o l y s i s . R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d i c i n a T r o p i c a l 2 6 : 1 - 4 , j a n - m a r , 1 9 9 3 .
T a b le 2 - C o r r e l a t i o n b e t w e e n m y o g l o b i n e m i a a n d r e n a l f a i l u r e in p a t i e n t s w i th te ta n u s . A c u te r e n a l N u m b e r M y o g lo b in e m ia
failu re p a tie n ts p o s itiv e n e g a tiv e
P re s e n t 7 2 5
A b s e n t 11 5 6
T o ta l 18 7 11
p = 0 .4 1 7
D IS C U S S IO N
A c u te re n a l f a ilu r e h a s n o t b e e n re c o g n iz e d as a fre q u e n t c o m p lic a tio n o f te ta n u s 621 23, e x c e p t fo r a v e r y s e le c te d s e rie s o f p a tie n ts a d m itte d to a r e s p ir a to ry u n it w h e re it w a s d ia g n o s e d in u p to 14% o f th e m 1017. In th e p re s e n t s tu d y w e re c o rd e d a c u te re n a l fa ilu re , o n th e b a s is o f s u d d e n in c re a s e in s e ru m c r e a tin in e in th e a b s e n c e o f e x tra -re n a l a z o te m ia , in 3 9 % (9 5 % C l, 23 to 6 0 ) o f p a tie n ts c o n s e c u tiv e ly a d m itte d to th e In fe c tio u s D ise a se H o s p ita l in S a lv a d o r-B a h ia -B ra z il. T h e p a tie n ts e n r o lle d in th is s tu d y w e re d ia g n o s e d as h a v in g g e n e ra liz e d te ta n u s g ra d e d a c c o rd in g to th e clin ic a i p re s e n ta tio n ; m in o r w o u n d s w e re th e m o s t fre q u e n t p o rta l o f e n tr y , n o t d iffe rin g fro m o th e r s e r ie s1 1.
T h e h ig h d e te c tio n o f a c u te re n a l fa ilu re in o u r se rie s is , p ro b a b ly , re la te d to th e sis te m a tic a lly p e r fo rm e d u r in a ly s is a n d d e te rm in a tio n s o f se ru m cre a tin in e , a t a d m is s io n a n d d u r in g th e fo llo w -u p . Im p o rta n tly , o n ly o n e o f th e p a tie n ts p re s e n te d o lig u ria ; th e m o s t fre q u e n t fo r m o f a c u te ren al
fa ilu re is n o n - o lig u ric a n d a h ig h d e g re e o f su sp icio n is n e c e s s a ry f o r th e d ia g n o s is o f th is c o n d itio n . It is p o s s ib le th a t th e p h y s ic ia n s c a r rin g f o r p a tie n ts w ith te ta n u s h a v e t h e i r a t t e n t i o n f o c u s e d o n th e n e u ro lo g ic a l m a n ife s ta tio n s o f th e d is e a s e a n d th e m ild a n d tra n s ie n t d e c re a s e o f re n a l fu n c tio n g o e s u n n o tic e d . A c u te re n a l fa ilu re h a s b e e n d ia g n o s e d o n ly in th e m o s t s e v e re ly a ffe c te d p a tie n ts 15, u su a lly o lig u ric , d e n o tin g a m o re a d v a n c e d sta g e o f th e d isea se . P o s s ib ly , u s in g a m o re s e n s itiv e m a rk e r o f re n al fu n c tio n th e p re v a le n c e o f a c u te re n a l fa ilu re
p ro b a b ly c o u ld b e h ig h e r th a n w h a t w a s re p o rte d in th e stu d y .
T h e in te n s e m u s c u la r w o rk is g en e ra lize d tetan u s
re s u lts in rh a b d o m y o ly s is , a s d e m o n s tra te d b y ris in g o f s e r u m le v e is o f c re a tin e p h o s p h o k in a s e , ald olase, am in o tra n sfe ra se s a n d lac to d e h y d ro g en a se,
in c lin ic a i a n d e x p e rim e n ta l s tu d ie s 2 5 8 18 22. In th e p re s e n t in v e s tig a tio n w e c o u ld n o t e s ta b lis h a c o r r e l a t i o n b e tw e e n a c u te r e n a l f a i l u r e a n d
r h a b d o m y o l y s i s a s d i a g n o s e d b y s e r u m c o n c e n tra tio n s o f m y o g lo b in g r e a te r th a n 1 2 0 u g /l o r, ev e n , b y e le v a te d s e ru m le v e is o f C P K , a m u c h m o re s e n s itiv e m a rk e r o f m u s c u la r in ju r y 11 14. M y o g lo b in u ria w a s n o t s e a rc h e d fo r; it c o rre la te s p o o rly w ith m y o g lo b in e m ia 12 19. T h e r o le o f r h a b d o m y o ly s is in th e p a th o g e n e s is o f th e a c u te re n a l fa ilu re in te ta n u s , h o w e v e r , c a n n o t b e n e g le c te d : th e r e m a rk a b le m u s c u la r in v o lv e m e n t a n d m y o ly s is a s a c o n s e q u e n c e o f to n ic c o n tra c tio n s o f m u s c u la r g r o u p s a n d fr e q u e n t a n d g e n e ra liz e d c lo n ic c o n tra c tio n s in a d d itio n to la rin g e a l sp as m s
a n d p r o f u s e s w e a tin g c a u s e a b n o r m a litie s in flu id , ele c tro ly te s a n d a c id -b a s e b alan c es. T h e s e m e ta b o lic a b n o rm a litie s , in a s s o c ia tio n w ith th e h e m o d y n a m ic in s ta b ility s e c o n d a ry to th e o v e ra c tiv ity o f th e s y m p a th e tic n e r v o u s s y s te m 13 s tro n g ly s u g g e s t a m u ltifa c to ria l p a th o g e n e s is f o r th e a c u te re n a l fa ilu re in te ta n u s . T h e d iffíc u lty in d e te r m in in g th e s p ec ifíc
ro le o f e a c h in d iv id u a l fa c to r in s u c h a m u ltifa c to ria l p a th o g e n e s is is w e ll k n o w n 3.
T h e la c k o f c o r r e la tio n b e tw e e n a c u te re n a l fa ilu re a n d s e v e rity o r /a n d m o rta lity o f te ta n u s w as n o t u n e x p e c te d . D if f e r e n t fr o m o th e r s e rie s w h e re th e d ia g n o s is o f re n a l fa ilu re w a s d o n e in s e v e re ly ill p a tie n ts , m o n ito r in g th e re n a l fu n c tio n fr o m tim e o f a d m is s io n w e c o u ld d e te c t a n im p a irm e n t o f re n a l fu n c tio n v e r y e a rly in th e c o u r s e o f th e d isea se .
In s u m m a ry , th is s tu d y re c o rd e d a c u te re n a l fa ilu re in 3 9 % o f p a tie n ts w ith g e n e ra liz e d te ta n u s. I t w a s , fr e q u e n tly , n o n - o lig u r ic , m ild a n d tra n s ie n t
a n d n o t re la te d to th e s e v e rity o f te ta n u s . A lth o u g h m y o ly s is , d e fin e d b y s e r u m in c re a s e s o f m u s c le en z y m e s, w a s fr e q u e n t ( 8 7 ,5 % ) , a d i r e c t c o r re la tio n b e tw e e n a b n o rm a l s e r u m le v e is o f m y o g lo b in a n d C P K c o u ld n o t b e e s ta b lis h e d , s u g g e s tin g th e ro le
o f o th e r fa c to rs in th e p a th o g e n e s is o f th e a c u te re n a l f a ilu r e in te ta n u s .
R E S U M O
M a r t i n e l l i R , M a t o s C M , R o c h a H . T e t a n u s a s a c a u s e o f a c u t e r e n a l f a i l u r e : p o s s i b l e r o l e o f r h a b d o m y o l y s i s . R e v i s t a d a S o c i e d a d e B r a s i l e i r a d e M e d i c i n a T r o p i c a l 2 6 : 1 - 4 , j a n - m a r , 1 9 9 3 .
d o s e x o m a s c u l i n o e 4 d o f e m i n i n o , c o m id a d e m é d i a d e 3 1 , 8 ± 2 , 0 a n o s . E x c e t o p o r p r o t e i n ú r i a l e v e a m o d e r a d a ( < lO O m g /d l) e m 9 p a c i e n t e s , o s s u m á r i o s d e u r in a f o r a m c o n s i d e r a d o s n o r m a is . C r e a ti n i n a s s é r i c a s s u p e r i o r e s a l , 4 m g / d l f o r a m o b s e r v a d a s e m 3 9 % d o s p a c i e n t e s , n í v e i s e l e v a d o s d e C P K e m 8 7 , 5 % e m io g l o b i n a s é r ic a m a i o r q u e 1 2 0 f i g / d l e m 3 9 % . O li g ú r i a f o i d o c u m e n t a d a e m a p e n a s u m p a c i e n t e ; n e n h u m p a c i e n t e r e q u e r e u tr a t a m e n t o d ia lí ti c o . N ã o f o r a m o b s e r v a d a s c o r r e l a ç õ e s e n t r e in s u f i c i ê n c i a r e n a l a g u d a e n í v e i s s é r i c o s d e m i o g l o b i n a e / o u C P K . A i n s u f ic i ê n c i a r e n a l a g u d a n o t é ta n o n ã o f o i in f r e q ü e n t e ; g e r a l m e n t e é n ã o - o li g ú r ic a , d e p e q u e n a g r a v i d a d e , t r a n s i t ó r i a e n ã o r e l a c i o n a d a à s e v e r i d a d e d a d o e n ç a o u a o s n í v e i s s é r i c o s d e m io g lo b in a e / o u C P K .
P a l a v r a s - c h a v e s : T é t a n o . R a b d o m i ó l i s e . M io g lo b in a . I n s u f i c i ê n c i a r e n a l a g u d a .
R E F E R E N C E S
1. A rm ita g e P , C liffo rd P . P ro g n o s is in t e ta n u s : u s e o f d a ta fro m th e ra p e u tic tr ia ls . J o u r n a l o f In fe ctio u s D is e a s e s 138:1-8, 1978.
2 . B a ru a A R , G h o sh B P . S tu d ies o n se ru m tran sa m in a se s a n d c re a tin e -p h o s p h o k in a s e in te ta n u s . J o u r n a l In d ian M e d ic a i A s s o c ia tio n 4 9 :3 7 6 - 3 8 0 , 1 9 6 8 .
3 . B rez is M , R o s e n S , E p s te in F H . A c u te r e n a l failu re . In : B r e n n e r B M , R e c t o r J r F C (e d s) T h e k i d n e y , 4 th e d itio n , W B S a u n d e r s C o m p a n h y , P h ila d e lp h ia p. 9 9 3 -1 0 6 2 , 1 9 9 1 .
4 . C a in s J A , M is s irlis E , W a lk e r W H C . U s e f u ln e s s o f se ria l d e te rm in a tio n o fm y o g lo b in an d c r e a tin e k in a s e in s e ru m c o m p a r e d f o r th e a s s e s s m e n t o f a c u te m y o c a r d ia l in fa rc tio n . C lin ic a i C h e m is try 2 9 :4 6 9 - 4 7 3 , 1 9 8 3 .
5 . C h o o -K a n g E , H a n n a W . S e ru m e n z y m e s c h a n g e s in te ta n u s . W e s t In d ia n M e d ic a i J o u r n a l 2 9 :1 9 1 - 1 9 7 , 1 98 0 .
6. E d m o n d s o n R S , F lo w e rs M W . In te n s iv e c a r e in te ta n u s : m a n a g e m e n t, c o m p lic a tio n s a n d m o rta lity in 1 0 0 c a s e s . B ritish M e d ic a i J o u r n a l 1 :1 4 0 1 -1 4 0 4 , 1 9 79 .
7 . G a m i e r M J , M a r s h a ll F N , D a v is o n K J, L e p r e a u J r F J . T e ta n u s in H aiti. L a n c e t 1 :3 8 3 -3 8 6 , 1 9 7 6 . 8 . G h a n e m M H , K h a d r A A , S h a r a b e e n M K , G u ir g is
F K . T h e s k e le ta l m u s c le in te ta n u s . J o u r n a l o f T r o p ic a l M e d ic in e a n d H y g ie n e 7 6 :2 3 9 - 2 4 2 , 1 97 3 .
9. G riffin J W . L o c a l te ta n u s . J o h n s H o p k in s M e d ic a i J o u r n a l 1 4 9 :8 4 -8 8 , 1 9 8 1 .
10. H a r ip a r s a d D , P a th e r M , R o c k e D A , W e s le y A G . R e n a l fu n c tio n in te ta n u s . I n te n s iv e C a r e M e d ic in e 1 0 :6 7 -7 0 , 1 98 4.
11 . H e s s J W , M a c D o n a ld R P , F r e d e r ic k R J , J o n e s R N , N e e rly J , G ro s s D . S e r u m c r e a tin e p h o s p h o k in a s e (C P K ) a c tiv ity in d is o r d e r s o f h e a r t a n d s k e le ta l m u s c le . A n n a ls o f I n te r n a i M e d ic in e 6 1 :1 0 1 5 - 1 0 2 0 , 1 9 6 4 .
12. K ag e n L , C h e id t S , R o b e rts L , P o r te r A , P a u l H . M y o g l o b i n e m i a f o l l o w i n g a c u t e m y o c a r d i a l in fa rc tio n . A m e r ic a n J o u r n a l o f M e d ic in e 5 8 :1 7 7 - 1 8 2 , 1 9 7 5 .
13. K e r r J H , C o r b e tt J L , P r y s - R o b e r ts C , S m ith A C , S p a ld in g J M K . I n v o lv e m e n t o f s y m p a th e tic n e r v o u s s y s te m in te ta n u s . L a n c e t 2 :2 3 6 - 2 4 1 , 1 9 6 8 . 14 . K o sk elo P , K ek k i M , W a g e r O . K in e tic b e h a v io r o f
1 3 1 1 -lab elled m y o g lo b in in h u m a n b e in g s . C lin ic a i C h e m ic a l A c ta 1 7 :3 3 9 - 3 4 7 , 1 9 6 7 .
15 . R a m a n G V , L e e H A . T e ta n u s a n d r e n a l fa ilu re . B ritish J o u r n a l C lin ic a i P r a c ti c e 3 8 :2 7 5 - 2 7 7 ,1 9 8 4 , 16 . S c h o fie ld F . S e le c tiv e p r im a ry h e a lth y c a r e :S tra te g ie s
f o r c o n tro l o f d is e a s e s in th e d e v e lo p in g w o rld . X X III. T e ta n u s : a p r e v e n t a b l e p r o b l e m . R e v ie w s o f In fe c tio u s D is e a s e s 8 :1 4 4 - 1 5 6 , 1 9 8 6 .
17. S e e d a t Y K , O m a r M A K , S e e d a t M A , W e s le y A , P a th e r M . R e n a l f a ilu re in te ta n u s . B ritis h M e d ic a i J o u r n a l 2 8 2 :3 6 0 - 3 6 1 , 1 9 8 1 .
1 8 . S tir n e m a n n V , S t ir n e m a n n H , R i c h t e r i c h R , L u n d s g a a r d -H a n s e n . S e r u m e n z y m e a c tiv itie s in c lin ic a i a n d e x p e r im e n ta l te ta n u s . E n z y m o lo g ia B io lo g ic a e t C lin ic a 8 :7 - 2 0 , 1 9 6 7 .
19 . S to n e M J , W ille r s o n J T , G o m e z - S a n c h e z C E , W a te rm a n M R . R a d io im m u n o a s s a y o f m y o g lo b in in h u m a n s e ru m . R e s u lts in p a tie n ts w ith a c u te m y o c a r d i a l i n f a r c t i o n . J o u r n a l o f C l i n i c a i In v e s tig a tio n 5 6 :1 3 3 4 - 1 3 3 9 , 1 9 7 5 .
2 0 . T a v a r e s W , S a d d y J C , A lf r a d iq u e M E M , F ria s L A M . E s t u d o d o s n í v e i s s é r i c o s d a c r e a tin o f o s f o q u in a s e e a l d o la s e e m p a c ie n te s c o m té ta n o . R e v is ta d o In stitu to d e M e d ic in a T r o p i c a l d e S ão P au lo 1 6 :1 8 9 - 1 9 6 , 1 9 7 4 .
2 1 . W e in s te in L . T e ta n u s . N e w E n g la n d J o u r n a l o f M e d ic in e 2 8 9 :1 2 9 3 - 1 2 9 6 , 1 9 7 3 .
2 2 . W e s le y A G , P a th e r M . T e ta n u s in c h ild r e n : a n 11 y e a r re v ie w . A n n a ls o f T r o p i c a l P a e d ia tr ic s 7 :3 2 - 3 7 , 1 9 8 7 .
