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2009

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ISBN 978-5-904769-01-7

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.
15.12.2009 .
60x90 1/16.
. 2000 . 583


:
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.
, ..

- , .
. Schein

,


-
,

( 1904 )
-

Sir Henry . Dale

( 1936 )

Sir John R. Vane

( 1982 )

-

Sir James W. Black

( 1988 )
2-
,
( )

Ryoji Noyori, William Knowles, . Barry Sharpless

( 2001 )

, S - - .

Barry J. Marshall,
J. Robin Warren
( 2 0 0 3 )

H e l i c o b a c t e r pylori

 I.

,
,
, , - .

, -
. ,
, ,
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.
,
APACHE (Acute Pathology Age Chronicle Health
Evaluation)

HP Helicobacter pylori

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2005 AstraZeneca
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( .. , 1968, .. , .. ,
1995):

1,5

1,2

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6,0

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90%
10 .
+

10

( . , 2000)

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. 1936 . Dale
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2

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.
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17

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90- XX ,
. , 450,
, - .
, 20-60
3-20 - .
,
. J.L. Smith
(1997),
5 20
94% 97%.
41-90%.
2

-
2

-
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1
.
, , 2

. - ,
2

, 15-25% .

-, 11,5%
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- .
2

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, .

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( ) - / - -
+

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.
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+

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+

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1974
, 1975 - - , 1979 .

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19

, I, II .

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4 - 5 .

/
/

24 96-

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.
1988
. ,

20

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4 .
, 4 18-20
100%
4 , - 8 .
- ,
,
14 .

.

-, ,
2

.

, - 5-10 .
2

80 - 98%, - - 50-75%.
2

J. Breiter (2000),

72% , - 66% .
-
2

56% 41% .
,
,

. 1983

,

21

Helicobacter pylori (HP),

.

.
, HP, ( )
. HP

.
,
HP .
(. . ) ,
,
, (), (). ,
in vivo,
HP- .
, .
HP, , .

. ,
,

(, ). ,
, HP,
.
(),
,
HP.
(7 )
, .

22

. (2000),
HP 90%. ,
HP,
, 98% (
) 82% (
). ,
,
-, 50%,
2

(Maastricht 2000)

1) 20 2

20 2

1) 20 2

20 2

1) 20 2

20 2

2) 500 2

2)
500 2

2)
120 4

3) 500 2

3) 1 2

3)
500 4

90%

3)
500 4

98%

-
HP ,
. (.. , 1995, D. Graham, 1996), HP
,


(.. ., 1999, .. ., 2002),
HP

23

,
.


. , G. Hasselgren (2004),
, , 40 , ,
> 4
14 , 12 , - 10 .

, , G. Armstrong (2004), . Lauritsen (2003), R. Miner
(2003)
(
> 4)
: , , , .

AstraZeneca ()
.
:
,
, ,
, .

.
0,3 /,

40 .
100%, ..
. 4
40 80 39
20 . -

24

.
,

( 1 - 2 ),

.
80
8 /,
6,0.

,
.
Hwan-Jeng Lin (1998), P. Netzer (1999) ,

. ,
1 6
. ,
4,5 5
.

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15 ,
,
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( )
.
-

25

.
-

. ,
-

20% ,

.

. ,


,

4 48-72 ,
- .

,
- ().

(): 1) 80
15-20 ; 2)
4-8 / 96 .

26

 III.

, 60-80%
. ,
10-15%
().

. , .. . (2002)
-
(1995-1997 .) 9,7%,
- 9,3%. ,
() 1991- 1997
. 56%, 1997
12,1%. X X I
:
2-2,5 (
- 6-12 )

(.. , 2006, .
. , 2002), 5,6 20,4% (N.
. Chou ., 2000; A. Garripoli ., 2000; . Sillakivi ., 2001).
.
2006 17,6%
5,9% 33,5%.

27

. , ,
2,5%.
,
,
. , ,
,
$3,1 ., 4 - ,
,
. ,
, ,

(- ).
-
.

(variceal bleeding) (nonvariceal bleeding) (. 2.1.).

.

: -
, -

.
,
, .
,
, .

:
1)

28

2)

3)

-,

. 2.1. ) ( ),
) (
)
-
, , .

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:
, - .
,
, 1704 Littre.

, - ,

1816 . 30- X I X

,
(Cruveilhier, 1829).

29

.

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-

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(); ) ,

30

(,

-)

.

5 15% ( 7-10%) .
, , 2007 8,65
. .
4 , .
,

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, 70-80 ,
- ,
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10 - 18%
.

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(
),
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.

() , , ,

31

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.

- ,
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7.
12-
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,
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+

,
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33

. R. Virchov
X I X
.

,
.
, , ,
circulus vitiosus:
- - -
- .

( ,
, ), (, , ), ,
. ,
,
,
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, ,
.
XX

,
, .
,
,
1983 . Marshall J. Warren
,
Helicobacter pylori, -
. 80- - 90-

,
Helicobacter pylori (HP).
34

- , ,
, Y. pestis V. cholerae. ,
-, , HP

80 - 90% , HP ,
( , ,
).
,
, HP.
, HP

. HP (, ,
), ,
. VacA HP, ,

, CagA-, , . 128 ,
. HP
, , ,
.
HP


.
, ,
, ,
(
), -

35

HP. ,
(
, 0(1) , , , ,
.),
(..
., 2002).
,

,
, .

,
. -
12%
, , 40 - 70%.
J. Heinkelein (1979)
.
1842
, . Curling .

1896 A. Eiselsberg, - 1867
Th. Billroth, . Cushing 1932
.
R. Virchov 1849 ,
. 1896
Dieulafoy ,
-
(. V).
, , ,

, ,

36

.
, ,

.
- -
X I X .
, -
XX . , A. Douthwait
J. Lintott 1938 . Lancet
, .
, 3 0 - XX
..

.
60- .

, -
- ,
. 1971 .
..

. ,
,
,
, - . 8 0 - 9 0 -
- :
,
,
. 1986
S. . Roth NSAID-gastropathy () - -

37

,
- . . . 1991
.
,
/
;
; -
;
.

,
.



,
- .
,-10-
: -:
, (Y 45.8, 25, 92).
( -
) . , (peptic ulcer) (ulcer disease)
.

, :
Helicobacter
pylori - D. Graham (1996). J. DelValle (1997)

,
,
/ . -

38

-
, , .
-
-.
-
-
.
, HP
, .
pylori- . ,

,
, , .


,
. , ,
-

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, -
,
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(2002) ..
, .. , .. .
. , -

39

-
.

,
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, ,
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, , -

.
() .
. ,
-1 -2
, . J. Vane (
) 1979 , -1
,
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. , -

40

- -
. :
8 .
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2

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2

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, .

.
, (
) .
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,
(. 2.2). ,

, ,
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.
- : 1) -

41

, 2) 3 .

. 2.2. -
-

()
,
20% .
-
. XX
. Finsterer ..
,
.
.

42

13%
.. ?
, ,
, .
, , , -,
.


.
,
15%,
40-60%
X X I . ,


,
.



.

J. Forrest (. 2.3.).

Forrest
,

(, , ),

(. 2.4.).

43

. 2.3. ].
Forrest (1985-95)

44

() ,
,
,
(. 2.5).

: 1)
(Forrest I ) ; 2)
(Forrest II - IIb),
(
),
( )
( ,
).

45

. 2.4. Forrest -
(LauJY,etal. 1998)

-
.
1. .
a) Forrest la:
- ,
- (

),
- ( , ,
, - ,
),
-
:
,

.

46

. 2.5. : )
, , Forrest lib; )
24
) Forrest lb:

- (

),
- -
, , , -
, ,
- .
2. :
) Forrest :

- ,
- , ,
, - , ,
- , .
) Forrest lib:

- ,
- , , -
, ,

47

- , .


(. 2.6.).

48

. 2.6. ) :
, ;
3/4 ; ) :
, ;
3/4 ; )
:

, ;
2/3

.

, ,
-

, .

,
4 (. 2.7).
,

49

. ,
, ,
. ,
,
(- , ), -.

. 2.7. :
, .
,

. McDougall (1977) . Bubrick (1978)

- , 2

. .. . (2001)
- , ,
1,5 2,2. , -

50

1,4 5,2 .
, -
2

, . S. Olivero . (1981) R. Spisni

(1986) , -
2

.
, R. Collins . (1985) ,

10%, - 20%.
, . McElwee (1979) . Ryberg (1990)

-, P. Hastings (1985) . Poleski (1986)
2

.
-
2

20%. 1992 Lancet

R.P. Walt
,

. 67
.
.
,
Forrest Ia-b Forrest Ila-b.
,
(=497),
10 ,
3,2 / 72 .

6
. ,
(=508),
,
. :
, , 51

, .
23,9%,
- 25,5%.
15,5% ,
17,1% , . ,
, ,
6,2%, , - 5,0%. ,

, (. 2.1).
,


. ,
, ,
2-
.

.
, ,
(
-!)
? ,
.
2.1.
(R.P. Waltetai,

52

1992)

, ,
-
2

,
R. Hinder . (1988) F.
Corragio . Okada (1984). .. . (2001)

0 , 2
2

20 . ,

, ,
()
.
- - .
2

1990-

- ().

1 2-
. R.P. Walt 1992
-

.

: 80 - 40 80 - 80 .
,
, 34,3 /.
80 + 40
2,1 /, 80 +
80 - 0,7 /. ,
-

53

4 90% 5% ,
. ,

.
- (, , ,
, )
. ,
, .
24
4 .
, -.
2

,
( - )

. ,

, .
1992 .. Daneshmend
-
.

(80 ) /

.
80 8 .
40
.
, ,
, ,
, -

54

(/),
.
, 1992 ,
:

.
.
- ! -, ..
Daneshmend
,
( ,
-, ..).
,
. -,

8- .
.. Daneshmend

-
, . ,
.. Daneshmend ,
.
,
-
.
1997 M.S. Khuroo
-

[8]. 220

, (Forrest Ia - 11,8%, Forrest Ib - 15,5%, Forrest IIa - 15,9%,
Forrest IIb - 56,8%).

55

,
,

, Forrest .
(Forrst I) .
: 5
40 / (!) 12 ,
6 .

,
, ,
,
. M.S. Khuroo
.
10,9% , - 36,4% (
, <0,001).
7,3% ,
23,6% , ( , <0,001).
20,1 % ,
(
- 2,.31,0) 70,9% , (
- 4,12,1).
,
, ,
5,5 1,8% ,
- 6,92,1 5,5% (
, >0,05).
, M.S. Khuroo
,


.
. ,

56

,
Forrest.
, ,
.
,

, , ,

, ,
. ,
,
Forrest la lb (
)
.

Forrest l i b . , ,

, ,


. , 12 ,
,
, ,
(
)
.

,
.

57

1990- - 2000- . . Lin et al. (1997), J.

Labenz et al. (1997), P. Netzer et al. (1999), K. Palmer et al. (2002), A. Barkun
et al. (2003) ,
,
,
(70 - 75%) ,
.

J. Y. Lau,

, 2005 .

, 72-
.
17 638
.
, (
,
),
(, 8 /) /
( - 80 / ) 72
40
8 . 12
,
(, ,
), .

() .

.
-

58

HP .
,
,
,
.
.
:
-
.

/ .
,
,
, ,
, , 30 .
. ,

:
60%
, 7% - - ,
.
(
) 19,1% ,
- 28,4% (=0,007).

22,5% , - 36,8% .

(9,26,0 )
(10,57,0 ), =0,3;
.
, -

59

,
(seu - ), , ,
(
). ,
, .
J. Y. Lau .
,

(Forrest I) , , .
,
,

. ,

.
- (
), ,
,
.
,

. ,
( -
) ,

.
2005 . Bardou . N. Barkun
- ,
(> 6 /),

60

, 1990
2003 .

(Forrest I - IIb).
- 1855 18
. ,
( 14.6%),
( 8.4%) (-5,2%).
,
20,6% ,
2- .

( 11.8%).
,
Forrest
I - lib ,
. ,
,
.
2- ,

, 3
24 ,
.
6

.
, , ,
,
: -
( ),
. ,
.

61

, , .
, -,

. -,
,

. ,

. -,
, -
. ,


. ,
, ,
, ()
.

.
0,3 /,

40 .
100%.
4 40 80
39 20 .


.
,
,

62

. 80
8 /,
6,0 .

- -
. A. Avgerinos (1995), . Erstad (2001), D.
Freitas (2000)
.
,
G-.
250 /
1,3-1,5
5,6-6 1 .
Y. Watanabe (1988), . Sommerville .
(1990).
88-100% ,
- 55-62% , -
90% . .. . (2001) ,
(6,0-6,3)
.
,

, 28%
. , F. Leung . (1989)

.
,
,

. ( ,

63

-) ,

.
, ,
,

- .

,
,
.


seu
.

- (Consensus Recommendations for Managing
Patients with Nonvariceal Upper Gastrointestinal Bleeding) [A. Barkun, M.
Bardou, J. K. Marshall et al.,_ 2003],
,
(. 2.2).
2.2.

- , 2003)

64

31 (

(-)

) 1001
.


(
) Z (
).
( 95%)
, - -

65

(

).

:
1.

III (. .).

2.

3.

APACHE III > 85

IV

:
1.

Dieulafoy

2.

Forrest I a, lb, II

3.

4.

5.

-.

, , I ,
APACHE I I I 65 ,
, 5
.
(.. , .. , 2004)

66

* - , 1 2 ,
,
.
,
( - )
,
( -
- ) (
- - ).

-
,
(. 2.3): I I I , ,
, II ,
, I, ,
.


,
, .

. , I I I , ,

67

. II

. I, , ,
,
(. 2.8.).
2.3.

(.. , .. , 2005)

,


,
.

-

68

[.. , .. ,
2003] (. 2.9.).

. 2.8.
,

962
.

, ..

.
:

69

. 2.9.

.
96
.

10 .

70

,
J. Forrest, , .

(, , ),

.

12,48 72
.


( 0 ) -
2

(-, Eh) .
0 . Eh
2

( 2241997)
, ,

, ,
.
7,2%
. 12
30,4% , 12-72 -
49,3% , 72 - 20,3% . 14,8%
I I I (
),
. , ( +
)
21,9% .

. ,
Forrest IIb

71

14,5%, Forrest II, lb 1

2-4 .
Forrest II
.
(. 2.4).
2.4.
( = 962)

Forrest
la

Forrest
lb

Forrest

Forrest
lib

Forrest
lie

100%

41,6%

67,9%

31,9%

87,5%

37,0%

50,9%

15,6%

50,0%

20,8%

32,7%

4,1%

28,4%
22,0%
13,9%

. 2.10. " " ()

,-,

72

,

.

.

92,5% - , 89,3%
, 81,2% 81,1%
45,0% ;

. -
.

,

.

. 72-
(. 2.10.) ,

6. ,
3,2
48 2,4 72
,
- ().
2

0 Eh
2

12 (1 )
(. 4.5).

, 0 ;
2

- , A Eh. -

73

-
: 0
2

-18,1%; A Eh +29,7%. 0
2

Eh :
0 -4,5%, A Eh
2

+10,2%. ,
-
.

(. 2.11).
0 Eh
( 12 )
2

. 2.11. (02)
(Eh)
,


.

74

21,9% .

. ,

. ,
,

. , ,

, ,
( I I I ) ,


- .

,

.

( ) ,

, (I ) ,
.

, ,
.
, I
, ; ,
II ;

, I I I ,
(. 2.12.).

75

. 2.12. : 1)
(I ); 2)
) (II ),
6) 72 / (I
); 3)
(III )
, ,
.
- ,
, 6
- 24-72
. : 72 6.
, 48
3, 72

76

2,5. , , -,
2

.
, 12 ,
30,4% ,
, 5.
-
-
.
,
-
,
0 Eh
2

. ,


.

.


(. 2.13).
,
, , / -.
+

,
, / -
+

- , 2

, ,
, . ,
2-,
24-72
,

77

() / -. ,
+

-
2

.
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(..
, .. , 1984). ,
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0 Eh ,
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.

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-

78

2-

( 2-3 )
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,

,
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. (1999), , 65%
,
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79

.
W.Smalley, . Griffin (1996)
2-
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(1996)

- 2- . J. Sung, .
Lee (2000)
- ,
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, 6,
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. (1999), G. Rodriguez et al. (1998), W. Wright (1999) ,
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81

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82

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1990-
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8 12
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. : 8
84 100 % .

, . 1993 G. Tildesley

-,
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.

A. Lanas 2-
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83

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) , /
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, .

O M N I U M (Omeprazol versus Misoprostol for NSAIDInduced Ulcer Management - C.J. Hawkey et a l l , 1998) ASTRONAUT (Acid
Supression Trial: Ranitidine vs Omeprazol for NSAID-Associated Ulcer Treatment
- N.D.Yeomans et all., 1998). O M N I U M
-,
ASTRONAUT -
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, 20 40 ,
,
. ,

. ASTRONAUT ,
,
20 / - . 2005 J. Goldstain ,
84

- , .
8 , ,
75,3 % , 20 40 - 86,6% 88,6% .

,
. 1980-
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1

.
,

.
. 1991
D. Graham ,
.
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- ,
. ,
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MUCOSA (Misoprostol Ulcer Complications
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. -
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85

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.
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86

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87

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88

(Consensus Recommendations for Managing Patients with
Nonvariceal Upper Gastrointestinal Bleeding*) [A. Barkun, M. Bardou, J. K.
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89

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90

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45

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94

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103

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105

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107

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108

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110

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112

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Chiba et a l , 1999).

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113

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114

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115

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117

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122

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123

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124

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125

, , ,
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et al. (1994) - 2200 , P. Hastings et
al. (1998) R. Fiddian-Green (1993) - 100 564
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126

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127

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1992 D. Cook ,
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128

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130

-. . Fennerty . (2002), .
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,
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131

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7 , 11 ,
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11,4 ,
- 23,6 . J. Delvin
(1999) ,

132

80%
, . . Erstad (1997) ,

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135

J. Richter (2001) P. Kahrilas . (2000),

40 /.
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139

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143

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144

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2005

2007 ,

J.J. Sung, PUB (Peptic Ulcer Bleeding),

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91 , 16 ,
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146

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30 ,
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147

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.
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vs.
(J.J.Sungetal,

2008)

()

72

5,9%

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30

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., .

589

935

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148

 () -

284

500

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,
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149

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150

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96
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,

151

, , (
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152

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153

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169


.., .., ..

..

. :

. .:

1999

..

( . B.C. ). ., 2004,

. 303-326.

.., .., ..

. ., 2000,575 .

. Consilium medicum,
2004, 6, 6, . 386-389.

.., .. -

. .

. Consilium medicum, 2004,

, 2003, . 30 - 94.

1,. 29-32.

., ..

.., ..

. .:

. , 2005, 13, 25, .

, 1992. . 362.

1668-1674.

.., ..
. .-.,
1996,370 .

, 1965, . 189 - 1 9 0 .
.., .., ..

.., .. .

.. . .,

. M.,
- , 2002,376 .

, 5 .2003 .) //

Abelo A., Andersson . ., Bredberg . et al. Stereo

, . .-

selective metabolism by human liver CYP en

2003.-4.

zymes of a substituted benzimidazole // Drug

.. -

Metab. Dispos. 2000. Vol. 28. P. 58-64.

Abelo A, Andersson , Antonsson M, Naudot AK,

. , 9, 13-14, 2001.

Skanberg I, Weidolf L. Stereoselective me

, , .

tabolism of omeprazole by human cytochrome

P450 enzymes. Drug Metab Dispos 2000; 28:

, ,

966-972.

Andersson T, Hassan-Alin M, Hasselgren G, R hss

K,

esomeprazole , the (S)-isomer of omeprazole.

. JAMA - Russia, 1998, 11 (1),

Clin Pharmacokinet 2001; 40:411-426.

. 32 - 35.

Weidolf L. Pharmacokinetic studies with

Andersson ., Bredberg E., Sunzel M. etal. Pharma

..

cokinetics and effect on pentagastrin stimu

//

lated peak acid output of omeprazole and its 2

, , -

optical isomers, S-omeprazole/esomeprazole

, 2002, 2, . 38-44.

and R-omeprazole//Gastroenterol. 2000.

.., .., ..,

Vol. 118.A1210

..

Bardou M, Toubouti Y, Benhaberou-Brun D, Rahme

. .: 50

E, Barkun AN. Meta-analysis: proton-pump

( . B.C.

inhibition in high-risk patients with acute pep

). ., 2003, . 248 - 258.

tic ulcer bleeding. Aliment Pharmacol Ther

CJ/L , ,
. ., 2000, 377 .

170

2005;21:677-686.

Barkun A, et al. Scand J Gastroenterol 2008; 43

(Suppl244):P11.
Barkun A., Bardou M., Marshall J._Consensus Rec
ommendations for Managing Patients with
Nonvariceal Upper Gastrointestinal Bleeding,
2003.
Castell D.O., Kahrilas P.J., Richter J.E. etal. Esomeprazole is more effective than lansoprazole for
treating daily and nocturnal heartburn (HB) in
GERD patients with erosive esophagitis (EE) //
J. Gastroenterol. Hepatol. 2002. Vol. 17
(Suppl.).A232.
Church N., Palmer K. Ulcers and nonvariceal bleed
ing. Endoscopy, 2003;35:22-6.
Creutzfeldt W. Chiral switch a successful way for
developing drug: Example of esomeprazole //
Z. Gastroenterol. 2000. Vol. 38. P. 893897.
Daneshmend TK, Hawkey CJ, Langmann MJS, Lo
gan RFA, Long RG, Walt RP. Omeprazole ver
sus placebo for acute upper gastrointestinal
bleeding: randomised double blind controlled
trial. BMJ 1992;304:143-147.
GentaR.M., Magner D.J., D'Amico D. Safety of longterm treatment with a new PPI esomeprazole
in GERD patients // Gastroenterol. 2000.
Vol. 118. A16.
Gerson L.B., Robbins A.S., Garber A. et al. A costeffectiveness analysis of prescribing strategies
in the management of gastroesophageal reflux
disease//Am. J. Gastroenterol. 2000. Vol.
95, 2. P. 395-407.
Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Ef
fect of acid and pepsin on blood coagulation
and platelet aggregation: a possible contributor
to prolonged gastroduodenal mucosal hemor
rhage. Gastroenterology 1978;74:38-43.
Hassan-Alin M., Andersson ., Bredberg E., Rohss
K. Pharmacokinetics of esomeprazole after
oral and intravenous administration of single
and repeated doses to healthy subjects // Eur.
J. Clin. Pharmacol. 2000. Vol. 56. P.
665-670.
Hasselgren G, Lind T, Lundell L, et al. Continuous
intravenous infusion of omeprazole in elderly
patients with peptic ulcer bleeding. Scand J
Gastroenterol. 1997;32:328-332.

Hasselgren G., Rohss K., Hedenstrom H. Effect of

esomeprazole 40 mg vs omeprazole 40 mg on
24-hour intragastric pH in patients with symp
toms of GERB. Digest. Diseases And Sciences,
Vol. 47, No. 5, 2002.
Hasslegren G., Hassan-Alin M., Andersson T. et al.
Pharmacokinetics of esomeprazole are unal
tered in the elderly // Gut. 2000. Vol. 47
(Suppl. III). A62.
Johnson D.A., Benjamin S.B., Vakil N.B. et al. Es
omeprazole once daily for 6 months is effec
tive therapy for maintaining healed erosive
esophagitis and for controlling gastroesopha
geal reflux disease symptoms: A randomized
double-blind, placebo-controlled study of
efficacy and safety // Am. J. Gastroenterol.
2001. Vol. 96. P. 27-34.
Kahrilas P.J., Kalk J.V., Johnson D.A. et al. Esome
prazole impoves healing and symptom i s o l a
tion as compared with omeprazole in reflux oe
sophagitis patients: A randomized controlled
trial // Aliment. Pharmacol. Ther. 2000.
Vol. 14. P. 1249-1258.
Kauffman GL, Conter RL. Stress ulcer and gastric
ulcer. In: Greenfield LJ, Mulholland MW, Old
ham KT, Zelenock GB, Lillemoe KD, editors.
Surgery: scientific principles and practice.
2nd ed. Philadelphia: Lippincott-Raven;1997.
p. 773-88.
Khuroo M., Yattoo G., Javid G. et al. A comparison
of omeprazole and placebo for bleeding peptic
ulcer. N. Engl. J. Med. 1997; 336:1054-1058.
Kromer W., Horbach S., Luhmann R. Relative effi
cacies of gastric proton pump inhibitors: Their
clinical and pharmacological basis // Pharma
cology. 1999. Vol. 59. P. 57-77.
Lanas A, Artal A, Bias J, et al. Effect of parenteral
omeprazole and ranitidine on gastric pH and
the outcome of bleeding peptic ulcer. J Clin
Gastroenterol. 1995;21:103-106.
Lau JY, et al. Effect of intravenous omeprazole on
recurrent bleeding after endoscopic treatment
of bleeding peptic ulcers. N Engl J Med., 2000,
343:310.
Lau JY, Leung WK, Wu JC, et al. Early administra
tion of high-dose intravenous omeprazole
prior to endoscopy in patients with upper gas-

171


trointestinal bleeding: a double blind placebo

Rohss K., Claar-Nilsson C, Rydholm H. Esomepra

controlled randomized trial. Gastroenterology

zole 40 mg provides more effective acid control

2005;128:Suppl 2:A-50

than lansoprazole 30 mg // Gastroenterol.

Lin HJ, Lo WC, Lee FY, Perng CL, Tseng GY. A Pro

2000.Vol. 118.A20.

spective Randomized Comparative Trial Show

Rohss K., Lind ., Wilder-Smith C. Esomeprazole (40

ing That Omeprazole Prevents Rebleeding in

mg) provides more effective intragastric acid

Patients With Bleeding Peptic Ulcer After Suc

control than lansoprazole (30 mg), omeprazole

cessful Endoscopic Therapy. Arch Intern Med,

(40 mg), pantoprazole (40 mg), rabeprazole (40

1998; 158: 54-58.

mg) in patients with gastro-oesophageal reflux

Lin HJ, Lo WC, Lee FY, Perng CL, Tseng GY. A Pro
spective Randomized Comparative Trial Show

symptoms. Eur. J. Clin. Pharmacol. (2004), 60:

531-539.

ing That Omeprazole Prevents Rebleeding in

Rohss K., Lundin C, Rydholm H., Nyman L. Es

Patients With Bleeding Peptic Ulcer After Suc

omeprazole 40 mg provides more effective

cessful Endoscopic Therapy. Arch Intern Med,

acid control than omeprazole 40 mg // Gut.

1998; 158: 54-58.

2000. Vol. 47 (Suppl. III). A63.

Lind ., Junghard O., Lauritsen K. Esomeprazole

Rohss K., Wilder-Smith C.H., Claar-Nilsson C. et al.

and lansoprazole in the management of pa

Esomeprazole 40 mg provides more effective

tients with reflux oesophagitis (RO): Combinig

acid control than standard doses of all other

results from two clinical studies // J. Gastroen

proton pump inhibitors // J. Gastroenterol. He

terol. Hepatol. 2002. Vol. 17 (Suppl.).

patol. 2002. Vol. 17 (Suppl.). A228.

A1024.
Lind ., Rydberg L., KylebackA. etal. Esomeprazole
provides imroved acid control versus omepra
zole in patients with symptoms of g a s t r o e
sophageal reflux disease // Aliment. Pharma

Rollhausen C. NSAIDs and upper gastrointestinal

bleeding. Endoscopy, 2003; 35: 372-3.
Rollhauser C, Fleischer D. Ulcers and nonvariceal
bleeding. Endoscopy, 1999,31 (1), p. 1 7 - 2 5 .
R hss K, Bondarov P, Lundin C, Nilsson-Pieschi C,

col. Ther. 2000. Vol. 14. P. 861-867.

Nyman L, Niazi M. Esomeprazole 40 mg ad

Marino P. The ICU Book. Philadelphia: Lea&Febiger,

ministered as a 30-minute intravenous infusion

1991.
Metz D. C. et al. Am. J. Gastroenterol. 2000; 95, 3:
626-633.(9)
Miner P et al. Am J Gastroenterol 2006;101:404-5
Miner Ph., Katz Ph., Cheng Y. Gastric acid control

provides the same effective acid control as oral

administration in healthy subjects [Abstract].
Gastroenterology 2003; 122 (4Suppl.):A-231.
Schonekas H. et al. Gastroenterology 1999; 116, 4
(Part 2):A305.(16)

with esomeprazole, lansoprazole, omepra-

Sneider H., Van Rensburg C, Schmidt S. et al.

sole, pantoprazole and rabeprasole: a five-way

Esomeprazole 40 mg administred intrave

crossover study. The Am. Journal of Gastroen

nously has similar safety and efficacy profiles

terology. Vol. 98. No. 12, 2003.

to the oral formulation in patients with erosive

Netzer P, Gaia C, Sandoz M, et al. Effect of repeated

injection and continuous infusion of omeprazole
and ranitidine on intragastric pH over 72 hours.
Am J Gastroenterol 1999;94:351-357.
Richter J.E., Kahrilas P.J., Johanson J. et al. Ef

esophagitis. Digestion 2004; 70: 250 - 256.

Sung JJ, etal. Aliment PharmacolTher2008;27:66677.
Sung J J, etal. Scand J Gastroenterol 2008;43(Suppl
244):Or19

ficacy and safety of esomeprazole compared

Talley N., Vanables ., Green J. Esomeprazole 40

with omeprazole in GERD patients with erosive

mg and 20 mg is efficacious in the long-term

oesophagitis: A randomized controlled trial //

management of patients with endoscopy-

Amer. J. Gastroenterol. 2001. Vol. 96. P.

negative GERD: A placebo-controlled trial of

656-665.

on-demand therapy for 6 months // Gastroen

terol. 2000. Vol. 118. A658.

172

Thomson A.B.R., Claar-Nilsson , Hasselgren G.

et al. Esomeprazole 40 mg provides more ef
fective acid control than lansoprazole 30 mg
during single and repeated administration //
Gut. 2000. Vol. 47 (Suppl. III). A63.
Tulassay Z., Kryszwski A., Dite P. et al. 7-day treat
ment with esomeprazole triple therapy eradi
cates Helicobacter pylori and heales patients
with duodenal ulcer disease // Gastroenter
ol. 2000. Vol. 118. A502.
Tulley N. J., Lauritsen K., Tunturi-Hihnala H. et al. Es
omeprazole 20 mg maintains symptom control
in endoscopy-negative gastro-oesophageal
reflux disease: A controlled trial of on-demand therapy for 6 months // Aliment. Phar
macol. Ther. 2001. Vol. 15. P. 347-354.
Tunturi-Hihnala H. et al. Esomeprazole 20 mg main
tains symptom control in endoscopy-negative
gastro-oesophageal reflux disease: A con
trolled trial of on-demand therapy for 6 months
// Aliment. Pharmacol. Ther. 2001. Vol.
15. P. 347-354.

clinical studies. Eur. Journal of Gastroenterol.

And Hepatol. 2005,17:191-197.
Wilder-Smith C, Rohss K., Lundin C, Rydholm H.
Esomeprazole 40 mg provides more effective
acid control than pantoprazole 40 mg / / J . Gas
troenterol. Hepatol. - 2002. - Vol. 17 (Suppl.).
-A7845.
Wilder-Smith C.H., Claar-Nilsson C, Hasselgren G.,
Rohss K. Esomeprazole 40 mg provides fac
tor and effective acid control than rabeprazole
20 mg in patients with symptoms of GERD // J.
Gastroenterol. Hepatol. - 2002. - Vol. 17 (Sup
pl.).-A612.
Wilder-Smith C.H., Rohss K., Lundin C. Esomepra
zole (E) 40 mg provides more effective acid
control than pantoprazole (P) 40 mg // Gastro
enterol. - 2000. - Vol. 118. - A22.
ZhonglinY. etal. J. Gastroenterol. Hepatol. 2002; 17
(Suppl): A257.(17).

Vakil N.B., Shaker R., Johnson D.A. et al. The new

proton pump inhibitor esomeprazole is effec
tive as a maintenance therapy in GERD patients
with healed erosive oesophagitis: A 6-months,
randomized, double-blind, placebo-controlled
study of efficacy and safety // Aliment. Phar
macol. Ther. 2001. Vol. 15. P. 927-935.
Walt RP, Cottrell J, Mann SG, Freemantle NP, Langman MJS. Continuous intravenous famotidine
for haemorrhage from peptic ulcer. Lancet
1992;340:1058-1062.
Walt RP, Reynolds JR, Langman MJ, Smart HL,
Kitchingman G, Somerville KW, Hawkey CJ. In
travenous omeprazole rapidly raises intragas
tric pH. Lancet 1992;340:1062-1068.
Van Pinxtern ., Numans M.E., Bonis A., Lan S.
Short-term treatment with proton pump inhibi
tors, H2-receptor antagonist and prokinetics
for gastroesophageal reflux disease-like symp
toms and endoscopy negative reflux disease //
Cochrane Database Syst. Rev. - 2000. - 2.
Wilder-Smith C, Bondarov P., Lindgren M. et al.
Intravenous esomeprazole (40 mg and 20 mg)
inhibits gastric acid secretion as effectively as
oral esomeprazole: results of two randomized

173