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BIOMAT., ART. CELLS, ART. ORG.

, 15(1), 287-295 (1987)


Artif Cells Blood Substit Immobil Biotechnol Downloaded from informahealthcare.com by Nyu Medical Center on 11/30/14

EFFECT OF tIgnOPggPUSIOU ON THE COURSE OF


DEMYELINIZATION PROCESSES: E X P E P Z ~ A LAND CLINICAL PICTURE

N.P. Metalnikova, A.A. S k o r o met s , N.M. Gurina, I.M. Barbas,


G.V. L i n ' k o v a , E.A.Gorokhov
Dep ar t men t of Nervous P r o b l e m s
P a v l o v Med i cal I n s t i t u t e
K a v et s k y I n s t i t u t e f o r Oncology P r o b l e m s
Leningrad
( R e c e i v e d September 1 2 , 19&b; r e v i s e d becember 2 4 , 1Y86)

SIJlQURY
For personal use only.

The e x p e r i m e n t s on g u i n e a p i g s w i t h e x p e r i m e n t a l a l l e r g i c
e n c e p h a l o m y e l i t i s showed, t h a t h e m o p e r f u s i o n t h r o u g h f i b r o u s and
g r a n u l a t e d a c t i v a t e d carbon r e s u l t e d i n s t a b l e c l i n i c a l e f f e c t
s o l e l y on t h e e a r l y stages of t h e d i s e a s e (10-11 d a y s a f t e r
s e n s i t i z a t i o n ) . A t t h e s t a g e of a d v a n c e d n e u r o l o g i c
s y m p t o m a t o l o g y t h e h e m o p e r f u s i o n p r o v e d e f f e c t i v e when p e r f o r m e d
t h r o u g h b i n a r y a d s o r b e n t on t h e b a s e o f f i b r o u s a c t i v a t e d c a r b o n
and i m m o b i l i z e d b a s i c e n c e p h a l i t o g e n o u s p r o t e i n .
F o r t y n i n e p a t i e n t s w i t h m u l t i p l e s c l e r o s i s unde rw e nt 2-3
s e s s i o n s of h e m o c a r b o p e r f u s i o n on SKN c o a l w i t h 7 d a y i n t e r v a l s .
In p a t i e n t s a t t h e i n i t i a l s t a g e of t h e d i s e a s e t h e
h e m o c a r b o p e r f u s i o n was f o u n d t o p r o d u c e a s t a b l e and p r a c t i c a l l y
c o m p l e t e n o r m a l i z i n g e f f e c t on t h e n e u r o l o g i c s t a t u s . A t t h e
a d v a n c e d s t a g e s of t h e d i s e a s e t h e h e m o s o r p t i o n e l i m i n a t e s o n l y
n e w l y d e v e l o p e d symptoms.
INTkODUCTIoN
E x p e r i m e n t a l a 1 l e r g i c e n c e p h a l o m y e l i t i s (EAE) i s a
l a b o r a t o r y model o f autoimmune p a t h o l o g i c p r o c e s s and m a n i f e s t s
c e r t a i n s i m i l a r i t y w i t h a number o f d e m y e l i z a t i o n d i s e a s e s of
human n e r v o u s s y s t e m ( m u l t i p l e s c l e r o s i s , a c u t e d i s s e m i n a t e d
e n c e p h a l o m y e l i t i s , L a n d r y - G u i l l a i n - B a r r e syndrome, e t c h The

Copyright @ 1987 by Marcel Dekker, Inc,


288 METALNIKOVA ET A L .

c u r r e n t methods used a t p r e s e n t t o treat t h e d e m y e l i n i z a t i o n


d i s e a s e s employ m o s t l y s t e r o i d hormones and immunodepressants and
show low e f f i c a c y . Some a t t e m p t s are d e s c r i b e d t o t r e a t m u l t i p l e
s c l e r o s i s by plasma exchange t r a n s f u s i o n (1,2) and
Artif Cells Blood Substit Immobil Biotechnol Downloaded from informahealthcare.com by Nyu Medical Center on 11/30/14

lymphocytopheresis (3). However, t h e a b o v e methods are r a t h e r


e x p e n s i v e and produce c o m p a r a t i v e l y s l o w r e g r e s s i o n of n e u r o l o g i c
d i s o r d e r s . The p o s i t i v e r e s u l t s r e p o r t e d f o l l o w i n g t h e
a p p l i c a t i o n of s o r p t i o n methods f o r organism d e t o x i f i c a t i o n
as a t h e r a p y of i n f e c t i o u s a l l e r g i c b r o n c h i a l asthma, p s o r i a s i s
and n e u r o d e r m i t i s , s y s t e m i c l u p u s e r y t h e m a t o s u s ,
g l omerul o n e p h r i t is , rheumatoid a r t h r i t i s and myas t h e n i a (4 ,5,6)
s u g g e s t t h a t hemocarboperfusion may be a l s o employed in t h e
t r e a t m e n t of immunodependent d e m y e l i n i z a t i o n d i s e a s e s of t h e
c e n t r a l n e r v o u s system.
The g o a l of t h i s s t u d y w a s t o assess t h e e f f i c a c y of
s p e c i f i c and n o n s p e c i f i c hemosorbents i n e x p e r i m e n t a l a l l e r g i c
e n c e p h a l o m y e l i t i s and a l s o t o e x p l o r e t h e f e a s i b i l i t y of
For personal use only.

hemosorption a p p l i c a t i o n as c u r a t i v e p r o c e d u r e i n m u l t i p l e
s c 1e r o s i s p a t i e n t s .

MA- AND HE'IPBODS


The EAE was induced i n g u i n e a p i g s by a d m i n i s t e r i n g t h e
b a s i c e n c e p h a l i t o g e n i c p r o t e i n , d e r i v e d from t h e p u r i f i e d m y e l i n
of t h e b o v i n e b r a i n w h i t e matter (7,8). The d e r i v e d p r o t e i n
p u r i t y was c o n t r o l l e d by h i g h p r e s s u r e l i q u i d chromatography,
u s i n g t h e p r o t e i n column "Protein-Pak" 1-125 ( s y s t e m " M i l l i p o r e -
Wathers", France). The male and f e m a l e mongrel g u i n e a p i g s , body
weight 300-400 g, were immunized by s u b c u t a n e o u s i n j e c t i o n (5
p o i n t s ) of 1.0 m l e n c e p h a l i t o g e n i c m i x t u r e , c o n t a i n i n g 100 ug
a n t i g e n i n 0.5 m l p h y s i o l o g i c s o l u t i o n and 0.5 m l Freund's
c o m p l e t e a d j u v a n t . A t e a r l y stages o f t h e d i s e a s e ( 1 1 t h day a f t e r
s e n s i t i z a t i o n ) o r i n t h e e v e n t of c h a r a c t e r i s t i c n e u r o l o g i c
p i c t u r e d e v e l o p i n g on 18-21 day (weight l o s s , i m p a i r e d f u n c t i o n
of p e l v i c organs, u n s t e a d y g a i t , p a r e s i s and p a r a l y s i s m o s t l y of
t h e hind e x t r e m i t i e s ) as w e l l as i n t h e i n t a c t a n i m a l s t h e s i n g l e
hemocarboperfusion was performed w i t h t h e rate 1.8-2.0 m l /min
through t h e microcolumns , c o n t a i n i n g 7.0 cm3 SKN-IK g r a n u l a t e d
carbon o r 1.2 mg f i b r o u s carbon a d s o r b e n t ACFM-Dnepr-MN. The
immunosorbent was made of a c t i v a t e d carbon f i b r o u s material
COURSE OF DEMYELINIZATION PROCESSES 289

(ACFM) w i t h i m m o b i l i z e d b a s i c e n c e p h a l o g e n i c p r o t e i n (2.0 mg
p r o t e i n p e r l g carbon matrix). According t o chromatographic
a n a l y s i s t h e i m m o b i l i z e d p r o t e i n c o n t a i n s l e s s t h a n 3% of
admixtures. Its d e s o r p t i o n from t h e carb o n m a t r i x i n t o
Artif Cells Blood Substit Immobil Biotechnol Downloaded from informahealthcare.com by Nyu Medical Center on 11/30/14

p h y s i o l o g i c s o l u t i o n , 1 M NaCl and 6 M u r e a s o l u t i o n s n e v e r
e x c e e d e d 1%. To f i l l t h e c o l u m n s d u r i n g t h e c o n t r o l e x p e r i m e n t
s u r g i c a l s i l k was u t i l i z e d . Number of a n i m a l s i n e a c h
e x p e r i m e n t a l g r o u p was 4-b.
To t r e a t m u l t i p l e s c l e r o s i s t h e h e m o s o r p t i o n a c r o s s SKN-IK
and SKN-2K c h a r c o a l w a s c o n d u c t e d 2-3 times w i t h 7 - d a y - i n t e r v a l
t h r o u g h veno-venous a c c e s s w i t h t h e r a t e of 100-120 m l/m in,
volume - 2-3 BCV. P a r a l l e l t o t h i s t h e p a t i e n t s were p r e s c r i b e d
v i t a m i n s of g r o u p B and u n d er wen t e x e r c i s e t h e r a p y , massage and
h y d r o t h e r a p e u t i c p r o c e d u r e s . The a n a l y s i s of n e u r o l o g i c
d i s o r d e r s ' d y n a mi cs i n t r e a t m e n t of m u l t i p l e s c l e r o s i s
a g g r a v a t i o n s by h e m o s o r p t i o n was made i n 49 p a t i e n t s aged 16-52
y e a r s ( f e m a l e s - 3 4 , males-15). Hemo s o r p tion was c a r r i e d o u t a t
For personal use only.

t h e d i s e a s e o n s e t i n 16 p a t i e n t s , a t s econd e x a c e r b a t i o n - i n 14
p a t i e n t s , i n t h i r d a g g r a v a t i o n - i n 8 p a t i e n t s , a nd a l s o i n 11
p a t i e n t s whose d i s e a s e h i s t o r y was o v e r 10 y e a r s w i t h f r e q u e n t
e p i s o d e s of a g g r a v a t i o n (1-2 times p e r y e a r ) .
A l l p a t i e n t s b e f o r e and a f t e r h er n o sorption s e s s i o n unde rw e nt
o p h t h a l m o s c o p y w i t h e x a m i n a t i o n of v i s i o n f i e l d s ,
e n c e p h a l o g r a p h y , e l e c t r o m y o g r a p h y and when t h e n e c e s s i t y arose -
c r a n i o g r a p h y , s p o n d i l o g r a p h y , e c h o g r a p h y and s c i n t i g r a p h y . The
n e u r o l o g i c s t a t u s was e v a l u a t e d by t h e s c a l e of S i p e e t a 1 (9).
The n o r m a l n e u r o l o g i c s t a t u s w a s t a k e n as 100 p o i n t s . I n a
c o n t r o l g r o u p , 25 m u l t i p l e s c l e r o s i s p a t i e n t s were t r e a t e d w i t h
c o n v e n t i o n a l t h e r a p e u t i c methods ( s t e r o i d hormones, c y t o s t a t i c s ) .

RESULTS
The e x p e r i m e n t s on g u i n e a p i g s showed t h a t i f t h e a n i m a l s
had c h a r a c t e r i s t i c p i c t u r e o f t h e d i s e a s e t h e n a s i n g l e
hemosorption procedure u s i n g g r a n u l a t e d o r f i b r o u s s o r b e n t l e d t o
t h e i r r e s t o r e d motor a c t i v i t y 24 h o u r s a f t e r t h e o p e r a t i o n ,
t h o u g h s h o r t l y a f t e r w a r d s t h e y d e v e l o p e d p a r e s e s or p a r a l y s i s and
d i e d 2-12 d a y s l a t e r (Fig.1).
F o l l o w i n g t h e p e r f u s i o n t h r o u g h t h e c olum n f i l l e d w i t h
s u r g i c a l s i l k t h e g u i n e a p i g s s t i l l m a n i f e s t e d EAE c h a r a c t e r i s t i c
290 METALNIKOVA ET AL.

!00
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80

60

40
For personal use only.

20

0
I5 25 3 5 4 0

Fig. I. Dynamics of paresis intensity in guinea pigs with


experimental allergic encephalomyelitis ( E M ) treated by
hemosorption through different adsorbents (shown on
individual animals).
1. hemosorption through SKN-IK in the presence of EAE
characteristic signs
2. hemosorption through ACFM in the presence of EAE
characteristic signs
3. hemosorption through SKN-K in the latent period
4. hemosorption through ACFM in the latent period
5. hemosorption through immunosorbent in the presence of
EAE characteristic signs
on abscissa axis - 24 hours after sensitization;
on ordinate axis - paresis intensity in points.
COURSE OF DEMYELINIZATION PROCESSES 291

symptoms and on t h e 18-20 day t h e y d i e d s i m i l a r l y t o t h e EAE


a n i m a l s w i t h o u t h emo car b o p er f u s i o n . A n i m a l s w hic h unde rw e nt
h e m o s o r p t i o n w i t h i n t h e l a t e n t p e r i o d ( 1 1 t h d a y ) by 18-19 d a y
-
a f t e r t h e s e n s i t i z a t i o n d i s p l a y e d o n l y EAE i n d i v i d u a l s i g n s
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weight l o s s , u n s t a b l e g a i t , impaired f u n c t i o n of t h e p e l v i c
o r g a n s . However, by 28-30 d a y a f t e r i m m u n i z a t i o n t h e i r c o n d i t i o n
seemed t o n o r m a l i z e w i t h o u t an y a d d i t i o n a l m e a s u r e s and l a t e r i t
reached p r o t r a c t e d remission period being a t p r e s e n t o v e r two
y e a r s (Fig. 1). I f t h e a n i m a l s d i s p l a y e d clear-cut pathologic
s i g n s t h e n h e m o s o r p t i o n p er f o r med t h r o u g h s p e c i f i c im m unosorbe nt
on t h e b a s e s of ACFM an d e n c e p h a l i t o g e n i c protein resulted i n
r e s t o r e d motor a c t i v i t y 24 h o u r s a f t e r t h e o p e r a t i o n (Fig. 1).
By 10-12 d a y a f t e r t h e s o r p t i o n t h e a n i m a l s d e v e l o p e d
e x a c e r b a t i o n accompanied w i t h a l l EAE c h a r a c t e r i s t i c s i g n s f o r
10-11 d a y s , and t h e r e a f t e r t h e s e v e r i t y of s y m p t o m a t o l o g y
d e c l i n e d and was f o l l o w e d by p r o t r a c t e d r e m i s s i o n (Fig. 1). When
h e m o p e r f u s i o n ( t h r o u g h a n y a d s o r b e n t employe d) w a s c a r r i e d o u t i n
For personal use only.

t h e l a t e n t p e r i o d (11 d a y ) t h e n by 17-18 d a y t h e g u i n e a p i g s
d i s p l a y e d o n l y w e i g h t l o s s w i t h o u t m a n i f e s t i n g a ny o t h e r EAE
s i g n s . By 20-21 d ay t h e i r w e i g h t was o b s e r v e d t o n o r m a l i z e t h e
s u b s e q u e n t g r a d u a l i n c r e a s e . Here i t s h o u l d be n o t e d t h a t i n t h e
i n t a c t a n i m a l s t h e h e m o s o r p t i o n p r o c e d u r e u s i n g f o r mass-
e x c h a n g e r f i 1l i n g a1 1 t h r e e t y p e s o f h emosorbe nt and t h e s u r g i c a l
s i l k l e d t o s l i g h t r e d u c t i o n i n body w e i g h t i n t h e f i r s t - t h i r d
day a f t e r t h e operation.
C l i n i c a l e x a m i n a t i o n of m u l t i p l e s c l e r o s i s p a t i e n t s
r e v e a l e d t h a t a l l t h e p a t i e n t s (100%) had motor d i s o r d e r s i n t h e
f o r m o f s p a s t i c p a r a l y s i s and p a r e s i s , 85% of p a t i e n t s s u f f e r e d
f r o m l a c k of c o o r d i n a t i o n i n body and l i m b m o t i o n s , 70%
m a n i f e s t e d d i s t u r b a n c e s i n s e n s i t i v i t y , and 50% i m p a i r e d v i s u a l
a c u i t y and f i e l d v i s i o n as w e l l a s t h e p a r e s i s of o c u l o m o t o r
nerves. Some p a t i e n t s had t r o p h i c m o d i f i c a t i o n s o f s k i n , h a i r ,
n a i l s and d y s f u n c t i o n of t h e p e l v i c o r g ans. The f i r s t s i g n s of
n e u r o l o g i c i m p r ov emen t s c o u l d be o b s e r v e d i n m u l t i p l e s c l e r o s i s
p a t i e n t s 2-3 h o u r s f o l l o w i n g t h e o p e r a t i o n s . They r e a c h e d t h e i r
maximum 24 h o u r s l a t e r and were p r e s e r v e d t i l l t h e n e x t
hemosorption session. A f t e r t h e second s e s s i o n t h e n e u r o l o g i c
s t a t u s w a s c o n t i n u i n g t o improve. The n e u r o l o g i c s t a t u s
q u a n t i t a t i v e a n a l y s i s made w i t h t h e a i d of t h e s c a l e S i p e e t a 1
292 METALNIKOVA ET AL.

(9) i n d i c a t e d , t h a t o p t i m a l r e s u l t s were r e c e i v e d i n t h e p a t i e n t s
w i t h d e s e a s e h i s t o r y up t o 2 y e a r s i n t h e i n i t i a l p e r i o d o r
s e c o n d a g g r a v a t i o n s t a g e ( T a b l e 1). T h ese p a t i e n t s showed
s i g n i f i c a n t i m p r o v emen t of t h e n e u r o l o g i c s t a t u s a f t e r t h e v e r y
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f i r s t h e m o s o r p t i o n s e s s i o n (Fig. 2). By t h e d a y of d i s c h a r g e t h e
number of p o i n t s by S i p e e t a1 s c a l e ( 9 ) r e a c h e d on a v e r a g e 84.
The p a t i e n t s were d i s c h a r g e d f r o m t h e c l i n i c w i t h m i l d n e u r o l o g i c
d i s o r d e r s , and some of them a p p e a r e d p r a c t i c a l l y h e a l thy.
The a s s e s s m e n t of t h e r a p e u t i c e f f i c a c y i n p a t i e n t s w i t h
disease history over 2 years revealed the following: i f the
n e u r o l o g i c d i s o r d e r s i n t h e p a t i e n t s a d m i t t e d t o t h e c l i n i c had
pronounced n a t u r e , t h e n no s t a t i s t i c a l l y s i g n i f i c a n t
m o d i f i c a t i o n s were o b s e r v e d a f t e r t h e f i r s t h e m o s o r p t i o n s e s s i o n .
The s i g n i f i c a n t i mp r o v emen t i n t h e c o n d i t i o n of t h e a b o v e
p a t i e n t s was n o t ed o n l y a f t e r t h e 2nd h e m o p e r f u s i o n s e s s i o n . By
t h e d a y of d i s c h a r g e , o n l y r e c e n t l y m a n i f e s t e d n e u r o l o g i c
symptoms were r e l i v e d . T h e r e was no ch ange i n n e u r o l o g i c a l
For personal use only.

s y s t e m s which were p r e s e n t f o r a l o n g time.


None of t h e p a t i e n t s d i s p l a y e d an y s o r t of c o m p l i c a t i o n s i n
t h e c o u r s e o f h e m o s o r p t i o n p r o c e d u r e s o r a f t e r them. A l l t h e
p a t i e n t s treated w i t h h e m o s o r p t i o n had no d i s e a s e e x a c e r b a t i o n s
w i t h i n t h e n e x t y ear .
I n t h e c o n t r o l g r o u p p a t i e n t s t h e d i s e a s e r e g r e s s i o n was
r e p o r t e d f o l l o w i n g 4 - w e e k - t h e r a p e u t i c c o u r s e , w h i l e in some c a s e s
no improvement was o b s e r v a b l e .

TABLE I
E f f i c a c y of Hemo s p o r t i o n T h er ap y Depending on Disease D u r a t i o n
---__ I- - - - ~ -
-I
S t a g e s of p a t i e n t e x a m i n a t i o n
Disease ad m i t t a n c e a f t e r 1st a f t e r 2nd discharge
duration session session

Under 2 y r s b4.8 i3.5 78.04 i4.4x 8 3 . 2 i4.6x 86.9 i3.3x


(12) (11) (10) (12)
Over 2 y r s 47.4 i4 . 8 57.7 -+ 5.5 74.5 + 4.7x 72.3+ 4.!jX
(12) (11) (11) (12)

x - a s i g n i f i c a n t d i f f e r e n c e from v a l u e s at a d m i t t a n c e ( p . 0.05)
I n parenthesis - number of o b e r s v a t i o n s
COURSE OF DEMYELINIZATION PROCESSES 293
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I00

90

80

70
For personal use only.

60

50 I 1 I
4
I 2 3 4

Fig. 2. N e u r o l o g i c s t a t u s dynamics i n t h e p r o c e s s of
hemosorption t r e a t m e n t of m u l t i p l e s c l e r o s i s p a t i e n t s .
on a b s c i s s a a x i s :
1. a d m i t t a n c e ; 2 - after 1 session; 3 -
a f t e r 2nd s e s s i o n
4 - d i s c h a r g e ; x - s i g n i f i c a n t d i f f e r e n c e from v a l u e s
reported a t admittance (~'0.05).
on o r d i n a t e a x i s :
p o i n t s on S i p e e t a1 s c a l e (1984).
294 METALNIKOVA ET AL.

DISCUSSION
The d a t a o b t a i n e d u n d e r e x p e r i m e n t a l and c l i n i c a l c o n d i t i o n s
s u p p o r t t h e h y p o t h e s i s framed e a r l i e r ( 4 ) on t h e p o t e n t i a l
e f f i c a c y of s o r p t i o n methods i n t h e t r e a t m e n t of d e m y e l i n i z a t i o n
Artif Cells Blood Substit Immobil Biotechnol Downloaded from informahealthcare.com by Nyu Medical Center on 11/30/14

diseases.
I n e x p e r i m e n t a l a1 l e r g i c e n c e p h a l o m y e l i t i s i n a n i m a l s a t t h e
e a r l y s t a g e s of t h e p a t h o l o g i c p r o c e s s (10-12 d a y s a f t e r
s e n s i t i z a t i o n ) a p p l i c a t i o n o f h e m o s o r b e n t s and i n t h e e v e n t of
h e m o s o r b e n t s w i t h a s p e c i f i c component, t h e l a t t e r b e i n g b a s i c
encephalogenic protein.
A s i t has been d i s c l o s e d e a r l i e r (11) i n t h e e x p e r i m e n t s on
guinea pigs t h e pretreatment with s i n g l e o r m u l t i p l e high doses
of h e t e r o l o g i c b a s i c e n c e p h a l i t o g e n i c p r o t e i n e x e r t e d d e f e n s i v e
a c t i o n i n r e s p e c t t o d e v e l o p m e n t of n e u o l o g i c sym ptom a tology and
m o r p h o l o g i c a l t e r a t i o n s i n t h e c e n t r a l n e r v o u s syste m . I n
a d d i t i o n t h e s e i n j e c t i o n s r e d u c e t h e i n c i d e n c e and i n t e n s i t y of
d e l a y e d s k i n r e a c t i o n s t o t h e b a s i c p r o t e i n and a l s o s t i m u l a t e
For personal use only.

p r o d u c t i o n of c o mp l emen t - b i n d i n g a n t i b o d i e s t o t h e a b o v e p r o t e i n .
The employment of ACFM-based s e c i f i c h em osorbe nt w i t h t h e
immobilized b a s i c encephalogenic p r o t e i n a l l o w e d t o a t t a i n s t a b l e
e f f e c t of h e m o p er f u s i o n i n g u i n e a p i g s w i t h c h a r a c t e r i s t i c
n e u r o l o g i c s i g n s of t h e d i s e a s e . i e ; w i t h i n t h e time p e r i o d s
d u r i n g which t h e n o n s p e c i f i c car b o n a d s o r b e n t s a p p e a re d
ineffective .
The f i n d i n g s o f o u r s t u d i e s s u g g e s t t h a t h e m o c a r b o p e r f u s i o n
t e c h n i q u e e m p l o y i n g n o n s p e c i f i c a d s o r b e n t s (SKN c h a r c o a l ) may be
u s e f u l i n m u l t i p l e s c l e r o s i s a t t h e s t a g e of a g g r a v a t i o n .
I n t e r e s t i n g l y , t h a t h e m o s o r p t i o n on SKN-IK c h a r c o a l , pe rform e d
d u r i n g 2-3 weeks w i t h a 2-3 d ay i n t e r v a l , a l s o p r e v e n t e d p r o g r e s s
of t h e d i s e a s e i n p a t i e n t s w i t h G u i l l a i n - B a r r e syndrome a t t h e
i n i t i a l stage. S i n g l e h e m o p e r f u s i o n t h r o u g h SKN c h a r c o a l c a r r i e d
o u t a t t h e s i g n s of r e s p i r a t o r y m u s c l e s ' p a r e s i s p e r m i t t e d t o
d i s p e n s e w i t h t h e a r t i f i c i a l l u n g v e n t i l a t i o n and t o d e c r e a s e i n
4-5 times t h e l e v e l o f c i r c u l a t i n g immune c o m p l e x e s i n t h e b l o o d
(12).
I t seems p r o m i s i n g t o e x p l o r e t h e f e a s i b i l i t y of c l i n i c a l
a p p l i c a t i o n of combined h e m o i m u n o s o r b e n t s on t h e b a s i s of
e n c e p h a l i t o g e n i c p r o t e i n an d c a r b o n f i b r e s w h i c h a p p e a r s t o y i e l d
p o s i t i v e r e s u l t s i n t h e t r e a t m e n t of p r o t r a c t e d d e m y e l i n i z a t i o n
d i s e a s e s of t h e n e r v o u s s y s t em.
COURSE OF DEMYELINIZATION PROCESSES 295

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b r a i n t i s s u e s t r u c t u r a l f o r m a t i o n s . Ukr. Biochim. Zhurn.,
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