Xvii Pedijatrijska Skola Zbornik Radova

XVII
XVII

XVII
8. 14. 2014. ,
XVII
, 8 - 14. 2014.
,
,

. ,
. ,

. . .
. -
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.

, .

8, 11070
: 011 31 08 116
: 011 26 97 232
E-mail: majkaidete@ptt.rs
Web: www.imd.org.rs

SMART Travel
43, 11000 Beograd
: 011 308 74 87, 308 66 94
: 011 308 66 95
E-mail: smart4@EUnet.rs
Web: www.smart4.co.rs
600
ISBN 978-86-85527-16-6

,
www.atelje.rs
..,
www.dosije.rs

XVII 63
, , .
, a
, , , ,
.
(, ),
.
, .
( . ?)

,, . ,
,
( ) .

,
a
.
, ,
.
,
,
( ).
(

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

,

) , ,
. ,
,
. , , ,
.

.
(, , , .) , ,
, .
, , ,
.
,
, ,
.
, ,
.
, 11. 2014.
,
,

............................................................................ 1
1.1.
- ....................................................... 3
,
1.2.
.................................................................... 13
,
1.3.

........................................................................... 18
-, ,

2. ............................................................................ 25
2.1. - , ............................ 27
-,
2.2.
.................................................................... 32
,
3. .............................................................. 39
3.1. -
.................................................................... 41

3.2. .................. 44
,
3.3. .................................. 47

3.4. - ............ 51
,
IX
- XVII
4. ...................................................................................... 57
4.1.
....................................... 59

4.2. ,
............................................ 65

4.3.
.................................................................................... 71

5.
. .............................................................................. 75
5.1. .............................. 77

5.2.
....................................................................... 82

5.3. ,
............................................................. 87

6. ..................................................................................................... 93
6.1. ................................................... 95

6.2. .......................................................... 99

6.3.
....................................... 103
-
6.4. : ...... 105
-
7. ......................................................................... 109
7.1. A A............................................................ 111

7.2. ......................................... 115
, ,
X
7.3. ............... 121

7.4. -
...................................... 125

8. ......................................................................................... 129
8.1.
............................................................................................... 131
. (: )
8.1. EVALUATION AND OUTCOME OF CHRONIC WET COUGH
IN CHILDREN.......................................................................................................... 134
Kostas N. Priftis
8.2. -
.......................................................... 136
,
8.3. ............................................ 142

8.4. ?............... 144

8.5.
..................................... 150
, ,
9. . ..................................................................................... 153
9.1. .................... 155

9.2.

....................................................................... 160

9.3. .............................................. 165

9.4. ...................................... 170

XI
- XVII
10. .......................................................................................... 175

10.1. ............................................................. 177
-
10.2. .................................................................................................. 182

10.3. - ............ 185
, -
11. ........................................................................................... 191
11.1. ,

......................................................................................................... 193
,
11.2. ..................................................... 198
,
11.3.
......................................................................................................... 203

11.4.
................................................ 207
,
12. ......................................................................................... 213
12.1. ................ 215

12.2. HENOCH SCHONLEIN ............... 222
,
12.3. ,
.................................................................................................... 225

13. ...................................................................... 229
13.1. ................................. 231

13.2. .................................................................................................. 234

13.3. ................................................................................................ 237
e
XII
13.4. ......................................................................................... 240

13.5. ............................................................. 244

14. ............................................................................... 249
14.1.
1 ................................. 251

14.2.
........................................................................... 257

14.3. - ?................................. 262
,
14.4. .............................................. 266
,
15. ......................................................... 271
15.1.
..................................... 273

15.2. - ................................ 278

15.3.
................................................................................................. 282

15.4. , ....................................... 287

16. ................................................................................... 293
16.1.
.............................................................................. 295
,
16.2. -

............................................................... 301

XIII
- XVII
16.3. . ?.................. 304

16.4.
?.................................. 309

17. ................................................................. 317
17.1.
.................. 319

17.2.
.............................................................................. 324

18. .................................................................................... 327
18.1. .......................................................................... 329
, ,
18.2. ..................................................... 335
,
XIV

.
,
,
dragana.bogicevic@udk.bg.ac.rs
. -

nenasci@gmail.com
. -
,
,
adoronjski@yahoo.co.uk
.
,
,
vlaskijovan@gmail.com
.
, , ,
,
avlaski@eunet.rs
.

,
,
dragana.vujic@imd.org.rs
.

,
,
vladislav.vukomanovic@imd.org.rs
XV
- XVII
.
,
,
sibil@ptt.rs
.
,
,
ema.golubovic@gmail.com
.
,
,
grebagreba@gmail.com
. .

,
sanja.grkovic@imd.org.rs
.
,
,
nikola.dimitrijevic@udk.bg.ac.rs
. . .

,
,
metabgen@imd.org.rs
.
,
,
milan.djukic@udk.bg.ac.rs
.

,
,
milena.djuric@imd.org.rs
.
,
,
szivic@medianis.net
XVI
.

,
,
nastava@imd.org.rs
. .
,

branka.petrucev@gmail.com
.

,
mira.ivanovic@stomf.bg.ac.rs
.
,
,
ida.jovanovic@udk.bg.ac.rs
.
,
,
dragana.janic@udk.bg.ac.rs
.

,
,
jankovib@gmail.com
. . .
,
,
maja.jesic@udk.bg.ac.rs
.
,
,
milos.jesic@udk.bg.ac.rs
. -
,
,
jadranka.privrodski@gmail.com
XVII
- XVII
.

svetlanajr@ptt.rs
.

,
olivera.jovicic@stomf.bg.ac.rs
.
,
,
jokic_rs@eunet.rs
.
,
,
bkamenov@yahoo.com
.
,
,
dt_dk2002@yahoo.com
.
,
,
ivanakavecan@gmail.com
.
,
,
srbgeorgios@gmail.com
.
,
,
nada.konstantinidis@gmail.com
.
,
,
gordanakostic@open.telekom.rs
XVIII
.
,
,
koleg@sbb.rs
.
, ,
,
acokos@gmail.com
.

,
,
jovan.kosutic@imd.org.rs
. . .

,
,
ruzica.kravljanac@gmail.com
.
,
,
zoran.krstic@udk.bg.ac.rs
. . . .

,
dragana.lozanovic@imd.org.rs
.

,
jekemandic13@gmail.com
.
,
,
julije.mestrovic@gmail.com
-
Drug Safety Leader, Hoffman La Roche, Basel Switzerland
XIX
- XVII
.

,
,
predrag.minic@imd.org.rs
. . .

drmarijamladenovic@gmail.com
.
,
,
bane.nestorovic@gmail.com
.
,
,
dimitrije.nikolic@udk.bg.ac.rs
. . .
,
tatjana.nikolic.65@gmail.com
.
,
,
sobradovic2@gmail.com
.

dragica.odalovic@gmail.com
. .
,
sonya@sezampro.rs
.

,
,
srdjan.pasic@imd.org.rs
.

pericd@ikomline.net
XX
.
,
,
amira@udk.bg.ac.rs
Kostas N. Priftis
Paediatric Respiratory and Allergy Unit,
3rd Dpt of Paediatrics of Athens University,
Attikon University Hospital, Athens, Greece
. . .
,
,
branka.radojcic@gmail.com
.
,
,
zoran.radojicic@udk.bg.ac.rs
.
,
,
n.radlovic@beotel.net
.
, - ,
,
jelena.roganovic1@ri.t-com.hr
.
,
,
silvija.sajic@udk.bg.ac.rs
. .
-, ,
sajkovski.aleksandar@gmail.com
.
, ,
,
msaraga@kbsplit.hr
XXI
- XVII
. -
, ,
, ,
msb@mefst.hr
. .

,
adsovtic@gmail.com
.

,
,
mila.stajevic@imd.org.rs
.
,
,
kcnis@eunet.rs
. .

,
stankovicz@gmail.com
.

,
,
stankovicpms@sezampro.rs
. .
,
stankovic_sandra@yahoo.com
. . .
,
tstankovic@medfak.ni.ac.rs
.
,
,
sasas@neobee.net
XXII
.
,
,
stojanovic@nscable.net
. .
, ,
vtasic@freemail.com.mk
. .
,
vcurcic@ikomline.net
.

mirjana.cukalovic@gmail.com
. e
,
,
dejan.skoric@udk.bg.ac.rs
XXIII
1.

:
. . .
:
.
1.
1.1.

-
,

,
,

,

. - ,
.
, ,

(1). , (2).

22. (
500 gr), .
30 (3, 4).

, ,
, .
, ( 7 )
(3,4).
3
2006. 6,5/1000 2015. (5,6).

2011. 8.8/1000, 22.2% (7.2/1000),
2006. 9.1/1000, 54% ( 5.9).

5 - , : , , ,
, .

,
, , , .
.

, 2008-2012. ,
.
13.3 12.3, 50%, 39%
104%, o 90% (6.5/1000
). (6.82) (6.85) ( 1).
1. 2008-2012.

1.
(8,99)
(8,57) (5,25) 71%, . 63%.
(3,5),
, 3,44 3,75 ( 2).
2. 2008-2012.

(6,69) ( 3,62) 85%, ( 3,0) 123%. (3,62)
(3,0) , , , , , ( 3).
3. 20082012.

, 2012.
59 (8 ) . 53 (1).

21 39,6% 500 /, . ,
,
, (1).
1. 53

< 500
21
39.6
500 999
15.1
1000 1499
17.0
1500 1999
13.2
2000 2499
5.7
2500 2999
1.9
3000 -3499
1.9
3500 6000
> 6000
5.7
, ( 2000
, ), 8 3
20.000, 1/3 .
, ,
, , ,
(7- 9).
, 2012. , 20.014 ,
68% (13.581 ) 2 : .
6
1.
, , , , , , , ,
, 9.356 , 45%
. ,
, , , , , 60%
.
, , , , , , 2012. 10078 , 3115 (30%)
. 6502 ,
, , ,
1000 . 517
, 153 . 2446 , 66%
- 1612, ,
.
16.664 ,
18043. 76%
5 - 6543 39,3%,
(1715), (1542), (1453)
(1401).

,
, .
19.078 , 29% . ( 33%) (34,4% ), (27,7%) . , ,
, . 60% . 30%
.

153 46,4% . 625 38,8%.

40% 37,6% .

2012. 869 (1,3%),
(235 ) (109).
, , 2012. 100
0,15%, 49 (1).

3789 ,
711 (10,5% ),
(11,6%), (15,5%) (10,1%).
2. ,
2012.
//
20014
5409
27,0
6262
31,3
1308
6,5
9356
2678
28,6
2178
23,3
521
5,6
1480
571
38,6
55
3,7
30
2,0
10078
2830
28,1
2548
25,3
489
4,9
6502
1905
29,3
383
5,9
367
5,6
2446
807
33,0
20
0,8
74
3,0
16664
4878
29,3
3557
21,3
1000
6,0
66540
19078
28,7
15003
22,5
3789
5,7
2012. (38.6%
), - 31.3% - 6.5%,
.
( 1.500 gr) 2,2%
(1.469 ) 2012. (7),
( 1.000 gr) 1083, 73%
. , ,
: 609 ( 1.500 gr), . 0,90% 2012. (1).
8
1.

, 32. (9). ,
,
,

(8). ,
,
. (10).
, 22,5% 15.003 , (6262) 42%
. . 24% ,
13%. 19%,
8,5%. 16%,
6,3% (1).
,
744 32. 2012. , 491 (66,7%) . 54% <37. , 73% <1.500 gr . ,
(

) (736) 179 24,3% .

, . ,
, 2013. .

30-40% .
80% . 30%
1.500 gr, , 88%,
80% (10).

,

.

(11-13),
200, 300
(14).
(24 )
( , ), (
).
, .

(1).
,
. 150-200.
, .
(1).
, , ( ), ,
(1).

.
.
. : ,
,
(11, 14, 15).
10
1.
, 689 , 282
, 71 .
, (
). , .
,
(
, ), , ( ,
, ). , (
), 5 ,
, , .
:
/, , ,

.
,
:
, ,.
,
- (4).
. , .
(
), ,
.
11
1. , , .

. .
2. , , . , , .
3. . . : . (). .
, , 2011; 8-15.
4. . . : . (). . :
; 2011; 16-22.
5. .
. : , (). XV , . , , 2012; 3-12.
6. . , 2006.
7. , devinfo.stat.gov.rs/rzsdevinfo/index.htm
8. European perinatal health report. PERISTAT 2008. www.europeristat.com
9. , , . ? : (.) 2011. , , 2012; 19-36.
10. :
. : . ().
. , , 2011; 23-25.
11. Cornette L. Contemporaty neonatal transport: problems and solutions. Arch Dis
Child Fet Neon Ed 2004; 89: F212-15.
12. Fenton CA, Leslie A, Skeoch CH. Optimising neonatal transfer. Arch Dis Child
Fet Neon Ed 2004;89:F216-25.
13. Langford S, Chabernaud JL, Petersen S, et al. Newborn transport around the
world. Sem Perinatol 1999; 4: 145-53.
14. World Health Organization regional office for Europe: European Strategic
Approach for Making Pregnancy Safer: Improving Maternal and Perinatal Health.
WHO. Geneva, 2008. www.euro.who.int/pubregea
15. Lupton AB, Pendray MR. Regionalized neonatal emergency transport. Sem
Perinatol 2004; 9:125-33.
12
1.
1.2.

,

,
70-
(1). -
( ), ( ).
,
, ,
(2).
. ,
(3).
(4,5).
,
,
(2). , - ,
2013. 2014.
.

(6,7,8).
. , 1981.
.

59 20 34% (7 )
500 , 500 1000
14 (23%) , 60% o (6). , 1000-1500
10 (17%), 1500-2000 7 (12%) , 2-3000
13
4 (7%) . ,
(1,2,4,5,6), , ( 1).
1.
(1)
( )
(2)
(3)

,
37. 2500 gr (
) (9).

( ; ). ,
.
24- .
, .
,
, , , ( ). /
.
( baby friendly; baby friendly+; mother friendly)

14
1.

: 2, 2 2-* .
2
350
35.
2.000 gr.
,
( ; ; Coomb ) .

( ),
( 1 6-8 ; 1
).
, .
2
350-1.000 34. 1.800 gr.
: ,
, , (
).
, . , 6
, 1-2 ( ).
(, , ) .
2
1.000-1.750 gr
, 32.
1.500 gr .
15
, ,
, , ( ).
- 24h / 7
( - ). < 32. .
(Neopuff), , ).
(3-4)
,
. (
, , ). .
2-3
, .
2+
1750 ( ).
(12-24h)
(CPAP; IPPV).
2- : (CPAP), - , ,
. , , , .

,
. , , 3- 3-.
3- - .
16
1.
(IPPV) , (, ) , , .
( 18) , (
).
. 24 h
1-2 ( 2 /1 ).
( ) , 24h , 24h.
3- 3- ( ) ( ) ( 3- ).
1. Committee on Perinatal Health. Toward Improving the Outcome of Pregnancy:

Recommendations for the Regional Development of Maternal and Perinatal
Health Services. White Plains, NY: March of Dimes National Foundation; 1976.
2. . : ().
. ,
, 2011; 23-25.
3. Yu YHV. Regional organization of perinatal care. Sem Perinatol 2004; 9:87-8.
4. Star AR. American Academy of Pediatrics. Committee on fetus and newborn.
Levels of neonatal care. Pediatrics 2004; 114:1341-7.
5. Canadian Paediatric Society. Levels of neonatal care. Paediatr Child Health 2008;
11:303-6.
6. Swiss Society of Neonatology. Standards for levels of neonatal care in Switzerland. 2012.
7. European perinatal health report. PERISTAT 2008. www.europeristat.com
8. , , . . : ().
. ,
, 2011; 35-92.
17
-, ,
1.3.

-, ,
,

,

( )
- - (The aby-freindly hospital initiative)

, , 2009. (1-3). ,
() 2012.

. , , .
e - (4),
1991. , 2009, 1994. ( ). 1994. ,
-,
2003. , (
-), .
,
( , , , .) -.
,
(mother-friendly) : 18
1.
,
,
,
.
.
, .
.
1.
11 :
1
2
3

4
5
,
6

7 , ,

8

9
( )

10
11
6

2015. . 5 . ,
19
-, ,
:
, , ,
, .
,
.
, ,
. , ( )
, ,
-, ,
, . :
2
7
- 5 ( )
5 ( )
8 ( )
8 ( )
9 ( )

:

: , , ,
, , , ;
: , , , ,
, , ;
, ,
;
20
1.
,
, , , , ,
, , , , , , , ,
;
, , , , , -
, ,
, (7,8,9);
, , ,
, , , , , , ,
,
,
, .
2.
5. baby friendly baby friendly + ( )
5.1.
.
.
5.2.
.
.
5.3.
.
.
5.4.
.
.
.
5.5. ()
.
.
.
5.6.
.
. /
.
.
.
.
21
-, ,

.
, , , , , , , , , .
. , , ,
, ,

. ,
: ,
, , , , , .

, , , , , .
,
, , , .

,
, ,

, . .
, .
.

. ,
, , .

.
.
,
(, , .) . , .
22
1.

. ,

. ,
,
(5), ,
- (6) , ,
.

,
2013. - (7) ,
,

, ,
.

.

.
, (
, )
,

.
. .
,
,
.
, , .

, ()
23
-, ,
. ,

.

.
1. . : .
. 18-21. , , 2011.
2. . - (he babyfreindly hospital initiative) . 2009 (
)
3. . , . : http://www.imd.org.rs/files/
uredba.pdf
4. . (he baby-freindly
hospital initiative). : http://www.who.int/nutrition/publications/
infantfeeding/bfhi_trainingcourse/en/
5. . 2015. .
: http://www.arhiva.srbija.gov.rs/vesti/2004-02/12/343584.html
6. , .
, .
, , 2011.
7. . - . :
8. http://www.akaz.ba/Standardi/Dokumenti/BFHI_Standardi_2013.pdf
24
2.

:
. -
2.
2.1. - ,

-,
,
,

.

.
, . .
. .
, . .

, , ,
. - , ,
,
, ,
, .

.
(1).
, ,
, , , ,
,
: , , , .
, .
(Human Genomic Project) .
. 2001. Nature Science. , , .
2004. ,
27
-,
22287.
0,1%. 2%
. 50%
. 1878 . 1, 2 580
. , . 255 , Y (2,3).
,
, . ,
. .
,
.

, , ,
. .
/ . 2005. .
: , , ,
. , .

,
,
.
, .
. .
.
,
.
, , , , (4,5).
, 2100.
, ,
,
, , , ,
28
2.
,
.

. ,
(5).
. ,
.

, , , ,
, , ,
.

(6).

.
.

.
.
. , . , ,
(7).

-
, . (7).
.
.
, . ,
. , -
.
, .
.
29
-,
.
, .

.

. , .
, ,
,
.

, , , , . , ,
(8,9).

. GWAS (Genome Wide Association Study)
.
, GWAS . .
. , . - (10).

, , . .
,
.

.
30
2.
1. Heard E, Martienssen RA. Transgenerational Epigenetic Inheritance: Myths and

Mechanisms. Cell 2014; 157:95-109.
2. Furrow RE, Feldman MW. Genetic variation and the evolution of epigenetic
regulation. Evolution 2014; 68:673-83.
3. Robinson MR, Wray NR, Visscher PM. Explaining additional genetic variation in
complex traits. Trends Genet 2014 ; 30:124-32.
4. Nicolini C, Bragazzi N, Pechkova E. Nanoproteomics enabling personalized
nanomedicine. Adv Drug Deliv Rev 2012; 64:1522-31.
5. Sayols-Baixeras S, Llus-Ganella C, Lucas G, et al. Pathogenesis of coronary artery
disease: focus on genetic risk factors and identification of genetic variants. Appl
Clin Genet 2014; 7:15-32.
6. Marciniak SJ, Lomas DA. Genetic susceptibility. Clin Chest Med 2014; 35:29-38.
7. Collard D, Kim SH, Osaki T, et al. Nano bioresearch approach by microtechnology.
Drug Discov Today 2013; 18:552-9.
8. Hu JK, Wang X, Wang P. Testing gene-gene interactions in genome wide
association studies. Genet Epidemiol 2014;38:123-34.
9. Schwenk RW, Vogel H, Schrmann A. Genetic and epigenetic control of metabolic
health. Mol Metab 2013; 2:337-47.
10. Hou L, Zhao H. A review of post-GWAS prioritization approaches. Front Genet
2013; 4:280.
31
2.2.

,
,

, ,
. .
. 99.9%
, 0.1% (
). .
. ,
,
,
. , (1).
. ,
. . , , .
.
.
, ( ), . ,
,

.
32
2.
-
-
(
) (2). , (.
single nucleotide polymorphisms, SNPs) (. simple sequence repeats,
SSRs).
. .
. , .

, - ,
. ( ,
, SNP , ) , ( , ) (3).

(. genome-wide association study, GWAS). .
(4).
.
.
,

-
. ,
. ,
, .
33

,
.
(5).
. :

,

.
, .
.

. . (
) .

, .

(VKORC1) p450 (CYP2C9) ( ), UGT11 ( )
(CPT-11)
TPMT ( -) (6-, )
,
(6).

. ( , , ).
34
2.
, . ,
, .
, , ,
, , .

.
(7).
, , ,
.

. .
-, ().
9 22. BCR-AB ,
. -
, . BCR-ABL
. (8).
.

,
.
,

. :
/ .
35
,
,
. in situ ex vivo in vivo. In situ
,
ex vivo (
), . In vivo
, , .
, ADA ( ). ,
, ,
.
,
2012. , Glybera (alipogene
tiparvovec), -. (9).

.

.
: , .
, ,
.
, .
1. Offit K. Personalized medicine: new genomics, old lessons. Hum Genet 2011;
130:3-14.
2. Pavlovic S, Zukic B, Stojiljkovic M. Personalizovana medicina. U: Antonic S,
Popovic A, urednici: Matine elije i genetika u slubi oveanstva. Univerzitetska
biblioteka Svetozar Markovi, Beograd, 2013; 8-26.
36
2.
3. Soon WW, Hariharan M, Snyder MP. High-throughput sequencing for biology

and medicine. Mol Syst Biol 2013; 9:640.
4. Drmanac R. Medicine. The ultimate genetic test. Science 2012; 336:1110-2.
5. Pavlovic S. TPMT gene polymorphisms: on the doorstep of personalized
medicine. Indian J Med Res 2009; 129:478-80.
6. Pavlovic S, Zukic B, Nikcevic G. Pharmacogenomics of Thiopurine SMethyltransferase: Clinical Applicability of Genetic Variants. In: Sanoudou D,
editor. Clinical Applications of Pharmacogenetics, InTech, Rijeka, Croatia, 2012;
75-94.
7. Pavlovic S, Zukic B, Stojiljkovic Petrovic M. Molecular genetic markers as a basis
for personalized medicine. J Med Biochem 2014; 33:1-14.
8. Stegmeier F, Warmuth M, Sellers WR, et al. Targeted Cancer Therapies in the
Twenty-First Century: Lessons From Imatinib. Clin Pharmacol Ther 2010;
87:54352.
9. Kastelein JJP, Colin JD, Ross CJD, et al. From Mutation Identification to Therapy:
Discovery and Origins of the First Approved Gene Therapy in the Western World.
Hum Gene Ther 2013; 24:47278.
37
3.
:
.
:
. . .
3.
3.1.
-

,
,

10.000 . 6 8
, 400.000 . 5.000
8.000 , .
.

,
( ).
,
.

.
(1:1000 )
.
. , , (1).
1.
1.

()
41

.

.
( , ,
) ( ).
1980. c
.
, 6 2
, -, . 1,
3, .
1 , , -
, 2, 3 1 (2).
() 1991. , ( ) 1.
(Cerezyme). 3000 (1,
2). , .
2 ( ). ,
. , (
), , - .
(2).

.
,
( 1, 2 , ).
42
3.
: -, -
- (-918).
- .
, .
1 (3).

-918. - .

II .
.
.
I (1).
,
40
( ), 6 ()
2 , 4 1 ( ), 3 ( ) 1 .

4 , . 250.000
300.000 .
( ).
. 4 ,
. (
).
1. Alfadhel , Thihli KA, Moubayed H, et al. Drug treatment of inborn errors of

metabolism: a systematic review. Arch Dis Child 2013; 98:45461.
2. Fumi K, Bari I, Mrsi M, i sar. Lizosomske bolesti nakupljanja - suvremena
dijagnostika i nove mogunosti lijeenja. Paediatr Croat 2004; 48(Supl 1):160-8.
3. Alfadhel M, Sirrs S. Enzyme replacement therapy for fabry disease: some answers
but more questions. Ther Clin Risk Manag 2011; 7:6982.
43
3.2.

,

,
,
() .
,
(1,2,3).
, () .
. ,
30.
, .
.

. : , , , ( , ) (2).

( , ) .
, .
()
,
, (2).

, ,
(4).
44
3.

30% .
,
.
, . : , ,
, , , , , , .
, , . (2).

. , , , ,
2 , (
) (1,3).
: ,
, , , -,
. (2).
.
: 1, , , , , 1 . (1,2,3).

: 1)
, ; 2) ; 3) , ,
; 4) ( );
5) .
,
, .
(1).
45

, ( )
.

. , , .

.
.
, , .
,
.
(1,2,3).
.
, .

. .
1. Clarke JTR. A Clinical Guide to Inherited Metabolic Diseases. 2nd ed. Cambridge
University press, Cambridge, 2004.
2. Saudubray JM, van den Bergh G, Walter JH. Inborn Metabolic Diseases, Diagnosis
and treatment. 5th ed. Springer Verlag, Hedelberg, 2012.
3. Hoffman GF, Zschocke J, Nyhan Wl. Inherited metabolic diseases a clinical
approach. Springer Verlag, Hedelberg, 2010.
4. Besley G. Prenatal diagnosis of inborn errors of metabolism. In: Walker JM, Rapley R
(editors): Medical Biomethods Handbook, Humana Press, New Jersey 2005; 607-23.
46
3.
3.3.

, ,
/
. 685 . 1-2
. / 4:1,
/ 3:2.
, , . , ,
, (1).
.
, . .
, , , .
,

( . , ).
, - ,
.
. , , , FGF23
. ,
.
(
ATP6V1B1 ATP6V0A4 -)
(2). - anion exchanger 1 (1) SLC4A1
. ,
, , .
, .
, , .
47
, . Schlingman .
2011 , CYP24A1 24 (3).
(),

,
.
.
. ,
, .
, ,
/.
, .
- , . . (SLC3A1,
SLC7A9). . , ( ).
. 24- ,
.
, .
. ().
; (4).
. ,
. .

,
, . T216M SLC3A1 ,
(5).

(6).
(0.5-1.0 mmol/1.73 m2)

.
> 1.0 mmol/1.73 m2. - PH1,
48
3.
PH2 PH3. AGXT, GRHPR HOGA.

,
. , : , , ,

( ). 1,30%
(7). , , , (8).
.
. , . . URAT1 GLUT9.
New Castle ( )
URAT1
(9). ,
, . (next generation sequencing)
2
.
, ,
(10).
.
.
1. Kokorowski PJ, Hubert K, Nelson CP. Evaluation of pediatric nephrolithiasis.

Indian J Urol 2010; 26:531-5.
2. Batlle D, Haque SK. Genetic causes and mechanisms of distal renal tubular
acidosis. Nephrol Dial Transplant 2012; 27:3691-704.
3. Schlingmann KP, Kaufmann M, Weber S, et al. Mutations in CYP24A1 and
idiopathic infantile hypercalcemia. N Engl J Med 2011; 365:410-21.
4. Tasic V, Lozanovski VJ, Ristoska-Bojkovska N, et al. Nephrotic syndrome occurring
during tiopronin treatment for cystinuria. Eur J Pediatr 2011; 170:247-9.
5. Popovska-Jankovic K, Tasic V, Bogdanovic R, et al. Molecular characterization of
cystinuria in south-eastern European countries. Urolithiasis 2013; 41:21-30.
49
6. Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med 2013; 369:649-58.

7. Hoyer-Kuhn H, Kohbrok S, Volland R, et al. Vitamin 6 in primary hyperoxaluria
I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol 2014;
9:468-77.
8. Cochat P, Hulton SA, Acquaviva C, et al. Primary hyperoxaluria Type 1: indications
for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant
2012; 27:1729-36.
9. Tasic V, Hynes AM, Kitamura K, et al. Clinical and functional characterization of
URAT1 variants. PLoS One 2011; 6:e28641.
10. Gucev Z, Koceva S, Marinaki A, et al. Lesch-Nyhan syndrome: a novel complex
mutation with severe phenotype. Clin Genet 2010; 78:296-7.
50
3.
3.4.
,
,
,
(2) .
1775 .
je ;
1780 .

;
1950 .
a ;
1951 .
;
1950-60 . ,
(),
;
1970 .
- - ;
1980 .
;
1980 .
-
;
2001 .
;
2001 .
.
, . . 200
.
:
, .
: ,
, ,
(1).
. , .
, , .
51
,
-, : , -,
. ,
.

. (, ),
.
( ). .
, 1-2% . : ,
. , (
, Q, )
. (2).
.
.
.
.

.

( , UV - .).
- 100%
. 100%
.
(), (3).
. ,
,
.
, , ,
52
3.
, , ,
. 100%
( ).
( ) , . , .
, . ,
21%
100% (4).

, 2001. (21% 2
100% 2) (5). : 1. 5.
; 2. / ( 30 ); 3.
; 4. . : 90.
(3).
2001 . ,
(ILCOR International Liaison Committee on Resuscitation, AAP American Association of Pediatrics ).
: ? ILCOR/AAP 2005 . :
. ,
21%
100%.
, .
60-90 .
20 , 110/ .
. European Resuscitation Councils life support 21%
: 60%, 70%, 80%, 85% 90% 2., 3., 4., 5. 10.
(6).
53
ILCOR/AAP 2010 .:
>32 e () .
90. . , .
<32 21-30% . <70% 5. /
, 100% .1
oxygen blender . .
,
. ,
.

.
100% . ,
30 .
, .
, . <27 .

:
: - .
, - - .
: ,
, ,
.
, :
5%. >29 50% 20-25% (3).
1 (<1000 )
89-94% ( 2011 .)
54
3.
:
,
21%
, .
(3,7).
:
.
():
, -
. ,
.
90%.

. . ,
.
1. Saugstad OD. The oxygen paradox in the newborn: keep oxygen at normal levels.
J Pediatr 2013; 163:934-5.
2. Saugstad OD, Sejersted Y, Solberg R, et al. Oxygenation of the newborn: a
molecular approach. Neonatology 2012; 101:315-25.
3. Saugstad OD. Resuscitation of newborn infants with room air or oxygen. Semin
Neonatol 2001; 6:233-9.
4. Sabir H, Jary S, Tooley J, et al. Increased inspired oxygen in the first hours of life is
associated with adverse outcame in newborns treated for perinatal asphyxia with
therapeutic hypothermia. J Pediatr 2012; 16:409-16.
55
4.
:
.
:
.
4.
4.1.

,
,
(- ), ( 7 ). ,
TORCH (, , ,
). -other
(-, 19, , , ). TORCH
.
, TORCH (1).
.

, (.
Polymerase Chain Reaction - PCR), .

G (IgG), M (Ig) ,
(Ig).
IgG Ig (t) 4-14 . , IgG
t
,
59
. , IgM t . , , IgM t
/ (1,2).
,
. IgM /
IgA ,
. , ,
2
.
, PCR (.
) (3).
IgG , - . t
,
IgG t. , IgG t 4-6 .
t
. ( t
t ). 80% ,
20% .

,
(2,4).
- , IgG ,
.
IgG t - .
Ig At ,
25% (1,2)
19 Ig At
7-14 , IgG At .
( ;
) ,
10-14 (2).

,
60
4.
.
( HBsAg, HBeAg, IgM anti HBc AT) (5).
( 18 ), (6).
(PCR)

( ) .
PCR . ,
. 20
( ).

. ,

(2,4).
,
. PCR
, , , (2).
PCR
Toxoplasma gondii (3).
PCR
( 19, , , , ) (2).
PCR 2-3 (6).

,
. ,
( ) (2).
, 1.
.
61
1.
PCR
PCR

IgG AT
PCR
PCR
19
PCR
PCR
PCR*
:
* 2-3.

TORCH

(1).
2. (1,2,6,7,8).
( )
. . sepsis like
, .
(1).
62
4.
2.
Sepsis like
s
/
**

19
TORCH
/ .

PCR .

- .
63
1. de Jong EP, Vossen ACMT, Walther FJ. How to use neonatal TORCH testing.
Arch Dis Child Educ Pract Ed 2013; 98:93-8.
2. Mendelson E, Aboudy Y, Smetana Z, et al. Laboratory assessment and diagnosis
of congenital viral infections: Rubella, cytomegalovirus, varicella-zoster virus,
herpes simplex virus, parvovirus B19 and human immunodeficiency virus.
Reprod Toxicol 2006; 21: 352-72.
3. Pinon JM, Dumon H, Chemia C, et al. Strategy for diagnosis of congenital
toxoplasmosis: Evaluation of methods comparing mothers and newborns and
standard methods for postnatal detection of immunoglobulin G, M and A
antibodies. J Clin Microbiol 2001; 39:2267-71.
4. Maniclal Sh, Emery VC, Lazzarotto T, et al. The silent global burden of
congenital cytomegalovirus. Clin Microbiol Rev 2013; 26:86-101.
5. Navabakhsh B, Mahrabi N, Estakhri A, et al. Hepatitis B virus infection during
pregnancy: Transmission and prevention. Middle East J Dig Dis 2011; 3:92-102.
6. Davison SM, Mieli-Vergani G, Sira J, et al. Perinatal hepatitis C virus infection:
diagnosis and management. Arch Dis Child 2006; 91:7815.
7. Pawlowska A, Swiatkowska E, Gliwicz D, et al. The role of cytomegalovirus infection
in pathogenesis of neonatal cholestatsis. Exp Clin Hepatol 2010; 6:25-9
8. Dsiliets V, Audibert F. Investigation and management of non-immune fetal
hydrops. J Obstet Gynaecol Can 2013; 35:e1-14.
64
4.
4.2. ,

,

, 85-90%
, 10-15%
(). ,
,
.

, , . , , .
, ,
( , ), (, ).
(, , , ).
,
(1,2,3).
,
. 30%, , , () .
, /
(1,2).
,
.
65
, ,
. ,
, . .
, 20 60
(2,3,4,5).
. ,
(1,2,3). ,
,
, (1,3).

,
.
,
,
(2,3). , ,
, (1,2).
,
,
.
, (2,3).
. , . , , (2,3,4)
, .

(5).
66
4.

() 1 2

, , . 3 .
, (S- skin, eyes, mouth)
45% . 80-85% . 10%
. . , 70% .
( S) 30% . , , , , ,
,
. 30-40% .
, .
25% .
m, ,
, ,
. , 60-75% .
2 20 , S
10-12 , 16 19 (1).

, 2
1 (5).
, 24
48 . ,

, .
30-50% (1,5).
67

( ) .
, , 36
, , ,
. (1,6).
,
.
.
6 , . , , .

.
. ,
(1).
()

.
()
I II , 28. .
, , . (- )
. , ,
, , . /
. ,
, , .
, ,
. 30% (7).
68
4.
III , , 2
(7).

(7).
5
2 ,
,
(7). ,
/ , ,

. , 30% (7,8).

, .
,
(7).

, . ,
,
.
, 48
(7).
(), 72-96
,
96 . (7,8).
,
. ,
(),
(7). ,
(7).
69
,
, , . , , (7).
1. Gomella T. TORCH infections (Toxoplasmosis, Rubella, Cytomegalovirus and Herpes

Simplex Virus). In: Gomella TL. Neonatology: Management, Procedures, On-call
problems, Diseases and Drugs, 6th ed, McGraw Hill, New York, 2009; 704-17.
2. Bonalumi S, Trapanese A, Mobili L, et al. Cytomegalovirus infection in pregnancy:
review of the literature. J Perinat Med 2011; 5:1-8.
3. Ludwig A, Hengel H. Epidemiological impact and disease burden of congenital
cytomegalovirus infection in Europe. Eurosurveillance, 2009; 14:1-7.
4. Lanzieri TM, Dollard SC, Josephson CD, et al, Breast milk-acquired
cytomegalovirus infection and disease in VLBW and premature infants. Peiatrics
2013; 131:1937-45.
5. Polin RA, Spitzer AR, et al. Infection and immunity. In: Polin RA, Spitzer AR,
editors. Fetal and neonatal secrets, Mosby, Philadelphia, 2001; 261-314.
6. Hollier LM, Wendel GD. Third trimester antiviral prophylaxis for preventing
maternal genital herpes simplex virus (HSV) recurrences and neonatal infection.
Cochrane database 2008, DOI:10.1002/14651858.CD004946.pub2
7. Smith CK, Arvin AM. Varicella in the fetus and newborn. Semin Fetal Neonat
Med 2009; 14:20917.
8. Duff P. Diagnosis and management of varicella infection in pregnancy. Perinatology
2010; 1:6-12.
70
4.
4.3.

,
,
()
. 1981.
- 25 ,
- 2 . , (1, 2).
, 2008 430 000
-, .
1985.
2013. 2962 -
1058 -. 4 7
,
. 1800 -,
a - 0,48% (1).

.
, a . :
) : ,
-1;
) : , CD4+ , ,
, , 4 ,
, ,
, ;
) : , ;
) : ;
) : , ,
, ,
6 (1).
71

15% 30% (3).
5 - 20%,
20 - 45%.
2% ,
.

:
(AZT), (3TC), (NVP) (EFV). , - CD4 + 350/3, ,
3 4 CD4 + (4).

,
( ). 14.
( 14. ).
: . , AZT , NVP , AZT 3TC; 7 , . 3 ,
14. .

.
38. .

NVP
6 . 10
/ 2,5 , 15
/ .
AZT NVP 6 .
4 / (4)
72
4.

. ,
, (5).
, CD+ T (6).

,
18 , 4-6
(1).
, , , 6 .
2,5

.
-
BCG,
. (HIB) ,
.
-
, IgG
18
. PCR
. , .

6 .
/- CD4+ T
200/3.
73
- CD4+ T .
1. Saharan , Lodha , Agarwal , et al. AIIMS- NICU protocols 2010. Perinatal

HIV. www.newbornwhocc.org, 4.04.2014.
2. UNAIDS/WHO. AIDS Epidemic Update. December, 2009.
3. The Working Group on Mother-to-Child HIV. Transmission of rates of motherto-child transmission of HIV-1 in Africa, America, and Europe: results from 13
perinatal studies. J Acquir Immune Defic Syndr 1995; 8:50610.
4. WHO. Rapid advice: Use of antiretroviral drugs for treating pregnant women and
preventing HIV infection in infants. WHO 2009.
5. Dunn DT, Tess BH, Rodrigues LC, Ades AE. Mother-to-child transmission of
HIV: implications of variation in maternal infectivity. AIDS 1998; 12:2211-6.
6. WHO. Rapid advice: Revised WHO principles and recommendations on infant
feeding in the context of HIV. WHO 2009.
74
5.

:
.
:
. .
5.
5.1.

,
,

, , , .
MySpace, The Crash Pad, ROFL Meebo
, , ,
, - .

. ,
, (1).

,
, . , . ( , , )
, , , (2).
cyberbullying.

, .
, , .
77

( 1).
, .

.
1.

(flaming)
( )

(spyware)
(sexting)
(happy slapping)

.

.
.

:
, ,

,
( )

?
78
5.

, , , .

,
. , .

. ,

, .

, .

,
.
, ,
.

,
.
, .
,
(2).

2013. , 26%
, 51% 77%
(2). 4.
, 28%
33% (2).
, 22%
30% (2).
79

.
9% 63% (3,4).

,
, ,
, (5).
,
, (, ) ( )
, ,
(5,6,7,8,9). (10).

, , . ,
, (8).

?

. , , ,
, ,
. .

:

,
,
80
5.

:
-- ,
-- ,
--
,
-- ,
-- .
(1).
1. Schurgin OKeeffe G, Clarke-Pearson K. Council on Communication and Media,

From the American Academy of Pediatrics. The impact of social media on
children, adolescents, and families. Clinical report. Pediatrics 2011; 127:800-4.
2. , . ,
. Telenor, , ,
UNICEF, , 2013, 165.
3. http://sbn.rs/clientpub/uploads/Digitalno%20nasilje-Izvestaj%202013.pdf
4. Williams K, Guerra N, Prevalence and Predictors of Internet Bullying. J Adolesc
Health 2007; 41:S14 S21.
5. Ybarra ML, Diener-West M, Leaf PJ. Examining the overlap in internet harassment
and school bullying: implications for school intervention. J Adolesc Health 2007;
41(6 Suppl 1): S42.50.
6. Tokunaga R. Following you from school: A critical review and synthesis of
research on cyberbullyng victimization. Comput Hum Behav 2010; 26:277-87.
7. Beran T, Li Q. The relationship between cyberbullying and school bullying. J Stud
Wellbeing 2007; 1:15-33
8. Juvonen J, Gross EF. Bullying experiences in cyberspace. J Sch Health 2008; 78:496-505.
9. Katzer C, Fetchenhauer D, Belshak F. Cyberbullying: who are the victims? A
comparison of victimization in the internet chatrooms and victimization in
school. J Media Psychol 2009; 21:25-36.
10. Bonanno RA, Hymel S. Cyber bullying and internalizing difficulties: above and beyond the impact of traditional forms of bullying. J Youth Adolesc 2013; 42:685-97.
11. Sourander A, Brunstein Klmek A, Ikonen M, et al. Psychosocial risk factors
associated with cyberbullying among adolescents: a population-based study.
Arch Gen Psychiatry 2010; 67:720-8.
81
5.2.

,
,
(1).
, , . ,
, , .
,
(2,3,4).
( ) , .
(, , ). , ,
, .
(2,3). , , .
, ,
() (5,6,7).
, .
. , , ,
.
, je
82
5.
1999. 340 .

, ,
. ,
, (
). 20-40
1000 .
.
. , ,
(1,2).
.
,
, .
.
, , .
,
.
, .
, .
. ,
, .
. ,
,
, ,
(9). , ,
(1,5,9). ,
- .
.
83

:
,
: , , ,
, ,
, , .
. ,

,
.
() 20 ,
.

,
, , ,
, . . , , ,
, .
, (
40%). 30% . .

, , .
, , , , .
84
5.
. . . ,
,
.
, , .
.
.
,
.
.

. 48-72 .
.

.
. , .
,
,
.
.
.

.
85
1. Shrier LA. Sexually Transmitted Infections: Chlamydia, Gonorrhoea, Pelvic

Inflammatory Disease, and Syphilis. In: Emans SJ, Laufer MR (editors): Pediatric
and Adolescent Gynecology, 6th ed. Lippincott Williams & Wilkins/ Wolters
Kluwer, Philadelphia, 2012; 32548.
2. Berlan ED, Emans SJ, O Brien RF. Vulvovaginal Complains in the Adolescents.
In: Emans SJ, Laufer MR (editors): Pediatric and Adolescent Gynecology, 6th ed.
Lippincott Williams & Wilkins/ Wolters Kluwer, Philadelphia, 2012; 30524.
3. Pienkowski C, Baunin C, Gayrard M, et al. Ovarian masses in adolescent girls. In:
Sultan C (editor): Pediatric and Adolescent Gynecology. Evidence-Based Clinical
Practice. Karger, Basel, 2004; 16382.
4. Sedlecki K, Stankovi Z, Maibrada I, et al. Microbiological features in peripubertal
girls with vulvovaginal complaints. 14th World Congress on Pediatric &
Adolescent Gynecology. Athens, 2004.
5. Sedlecki K, Maibrada I, Stankovi Z, i sar. Juvenilna metroragija. U: Marjanovi
B (urednik): Problemi u pedijatriji 2001, Zavod za udbenike i nastavna sredstva,
Beograd, 2002; 293-305.
6. Savi D, Stankovic Z, Djukic M, et al. Torsion of ovarian malignanat tumors in
childhood and adolescence. J Pediatr Endocrin Metabol 2008; 21:1073-78.
7. Laufer MR. Gynecologic Pain: Dysmenorrhoea, Acute and Chronic Pelvic Pain,
Endometriosis, and Premenstrual Syndrome. In: Emans SJ, Laufer MR (editors):
Pediatric and Adolescent Gynecology, 6th ed. Lippincott Williams & Wilkins/
Wolters Kluwer, Philadelphia, 2012; 23871.
8. Bristow RE, Nugent AC, Zahurak ML, et al. Impact of surgeon specialty on
ovarian-conserving surgery in young females with an adnexal mass. J Adolesc
Health 2006; 39:4116.
9. Menon S, Sammel MD, Vichnin M, et al. Risk factors for ectopic pregnancy:
a comparison between adults and adolescent women. J Pediatr Adolesc
Gynecol2007; 20:181-5.
86
5.
5.3. ,

,

. , ,
.
, , , .
, , , , , ,
. , () () .
,
, , .
, ,
. , ,
.
, -, .
/,
.
. - .
,
, ,
(1).
, , , ,
, . ,
(2).
, . ,
87
, ,
, ,
.
, ,
, .
, . , , ,
, , ...
.
, , ( ,
)
. . ,
, (,
), , .
, . ,
, .
,
, , , , () () , (3). , , .
,
. , .
,
(4).

, - . , ,
, ,
, .
. , , .
88
5.
, , , , , .
, ,
. .
,
. (),
,
Facebook-, .
, , .
,
, , , .
, , .

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

. . , , ,
89
(, , , ). .
,
.

,
. , ,
, (5). , , ,
,
.
, , ,
.
, . ,
,
HIV-, .

,
. , , ,
, , .
, , , . , ,
,
, , . ( ,
, parcour) ,
.
, , .

: .
90
5.
1. Ladame F. Les ternels adolescents comment devenir adulte. Paris: Odile Jacob;
2003.
2. . / , /
. : (): . , , 2005; 11-18.
3. Jeammet P. Adolescence et processus de changement. In: Widlcher D: Trait de
psychopathologie. PUF, Paris, 1994; 687-726.
4. . () . :
(): , , , 2010; 29-39.
5. . . : ():
, , , 2013; 114-127.
91
6.
:
.
:
. . .
6.
6.1.

,
,
.
1,4 .
7 gr/dl, ,
4,4-4,8 gr/dl. , . (-), ,
, C- (1).
-/ 1
(sodium-glucose linked transporter 1, SGLT1),
/ 2 (glucose transporter 2, GLUT2). , (2). ,
. ,
- ,
, -1- -4-, (2).
, , (2).
,
, , , ,
(Lactobacillus i Bifidobacterium) (2).
,
(2). , , . ,
(2).

. , ,
, (1, 3). , . ,
(1). ,
95
(1, 3). , , ,
(3).
2 (2q21),
3435. (1, 3).

, 3-7
(3). 5-10% (3).
2-50%, 50 100%,
(4, 5).
, 75% , C6 (minichromosome maintenance complex component
6) (3, 4, 6).
, ,
C6
(7, 8). , , , ,
(7, 8). ,

, 10000 , .
(4, 6, 7, 9).
, (7, 8, 10). C/T-13910,
G/C-14010,
T/G-13915, C/G-13907 T/C-13913 (3-8, 10).
, , (1-4, 6).
, , ,
, , , , (3).
(4, 6).

(LTT), .
(2 gr/kg, 50 gr) (1-3, 5). ,
96
6.
LTT (<20 mg/dl)

(6).
pH (<5,5) (>0,5%) (2).
H2 (lactose H2 breath test)
(>20 ppm)
(1-3). ,
.
, , (2). ,

, , (1). ,
,
,
(1, 3, 5, 6).
, , ,
(1, 6).
(1, 3, 6).

(1, 3).
1. Naim HY, Zimmer KP. Geneically deermined disaccharidase deficiency. In:

Kleinman RE, Sanderson IR, Goule O, Sherman PM, Mieli-Vergani G, Shneider
BL, editors. Walkers Pediatric Gastroenterointestinal Disease, 5th edition.
Hamilton: BC Decker Inc, 2008: 275-87.
2. Radlovi N. Nepodnoenje disaharida. Srp Arh Celok Lek 2010; 138:777-82.
3. Di Rienzo T, DAngelo G, Daversa F, et al. Lactose intolerance: from diagnosis to
correct management. Eur Rev Med Pharmacol Sci 2013;17 Suppl 2:18-25.
4. Gerbault P, Liebert A, Itan Y, et al. Evolution of lactase persistence: an example of
human niche construction. Philos Trans R Soc Lond B Biol Sci 2011; 366:863-77.
5. Khabarova Y, Torniainen ST, Nurmi HA, et al. Prevalence of lactase persistent/
non-persistent genotypes and milk consumption in a young population in northwest Russia. World J Gastroenterol 2009;15:1849-53.
6. Mattar R, de Campos Mazo DF, et al. Lactose intolerance: diagnosis, genetic, and
clinical factors. Clin Exp Gastroenterol 2012; 5:113-21.
7. Enattah NS, Jensen TG, Nielsen M, et al. Independent introduction of two lactasepersistence alleles into human populations reflects different history of adaptation
to milk culture. Am J Hum Genet 2008; 82:57-72.
97
8. Friedrich DC, Santos SE, Ribeiro-dos-Santos AK, et al. Several different lactase
persistence associated alleles and high diversity of the lactase gene in the admixed
Brazilian population. PLoS One 2012; 7:e46520.
9. Hollox E. Evolutionary genetics: genetics of lactase persistence--fresh lessons in
the history of milk drinking. Eur J Hum Genet 2005; 13:267-9.
10. Jones BL, Raga TO, Liebert A, et al. Diversity of lactase persistence alleles in
Ethiopia: signature of a soft selective sweep. Am J Hum Genet 2013; 93:538-44.
98
6.
6.2.

.
, ,
, . ,
, ,
.
, , ,
. ,
, . ,
, , , (1). ,
DNK, (1,
2). ,
, , , .
, ,
,
usnih (3, 4).
, .
(single nucleotide polimorphysm, SNP) . DNK
, .
, (1). , (MTHFR)
, . , ,
C667T MTHFR,
99
S- , , kao
.
, ,
, (5). ,
SNP
, , , , .
.
, , , .
. Micoarrey ,
, ,

. , ,
.
, ,
, ,
. (6). . PPAR (peroxisome
proliferator activated receptor, )
. , . S , , (7).

, , .
. ,
,
Prader-Wll, Bardet-Bedl, Alstrom , , , ,
.
100
6.
. , ,
.
, ,
. S ,
(8).
, , , , , ,
,
. ,
, , ,
, (9).
, . , , . -
, Mn - .
, B12, , , , , (9, 10).
,
. . ,

, ,
,
.
1. Ordovas JM, Corella D. Nutritional genomics. Annu Rev Genom cs Hum Genet
2004; 5:71118.
2. Choi SW, Friso S. Epigenetics: A New Bridge between Nutrition and Health.
Adv Nutr 2010; 1:8-16.
3. Gluckman PD, Hanson MA. Developmental origins of disease paradigm: a
mechanistic and evolutionary perspective. Pediatr Res 2004; 56:311-7.
101
4. Mc Millen IC, Robinson JS. Developmental origins of the metabolic syndrome:

Prediction, plasticity and programming. Physiol Rev 2005; 85:571-633.
5. Esfahani St, Cogger EA, Caudill MA. Heterogeneity in the prevalence of
methylenetetrahydrofolate reductase gene polymorphisms in women of different
ethnic groups. J Am Diet Assoc 2003; 103:200.
6. Afman L, Mller M. Nutrigenomics: From Molecular Nutrition to Prevention of
Disease. J Am Diet Assoc 2006; 106:569-76.
7. Feige JN, Gelman L, Michalik L, et al. From molecular action to physiological
outputs: peroxisome proliferator-activated receptors are nuclear receptors at the
crossroads of key cellular functions. Prog Lipid Res 2006; 45:12059.
8. Garver WS, Newman SB, Gonzales-Pacheco DM, et al. The genetics of childhood
obesity and interaction with dietary macronutrients. Genes Nutr 2013; 8:271-87.
9. Ong TP, Moreno FS, Ross SA. Targeting the Epigenome with Bioactive Food
Components for Cancer Prevention. J Nutrigenet Nutrigenomics 2012; 4:275-92.
10. Wells PG, McCallum GP, Chen CS, et al. Oxidative stress in developmental
origins of disease: teratogenesis, neurodevelopmental deficit, and cancer. Toxicol
Sci 2009; 108:4-1.
102
6.
6.3.

-
Drug Safety Leader, Hoffman La Roche, Basel Switzerland

(1). , .

. : ( B, HDL), , ,
. 25% ,
60 40%.
,
.
, , ,
.
,
(2-4).
1970-2000. (5, 6).
,
.

.
,
, , (7).

,
103

(8).
1. Gami AS, Witt BJ, Howard DE, et al. Metabolic syndrome and risk of incident
cardiovascular events and death: a systematic review and meta-analysis of
longitudinal studies. J Am Coll Cardiol 2007; 49:4031.
2. Kollias A, Skiliros E, Stergiu GS, et al. Obesity and associated cardiovascular risk
factors among schoolchildren in Greece: a cross-sectional study and review of the
literature. J Pediatr Endocrinol Metab 2011; 24:929-38.
3. Krawczynski M, Walkowiak J, Krzyzaniak A. Secular changes in body height and
weight in children and adolescents in Poznan, Poland, between 1880 and 2000.
Acta Paediatr 2003; 92:27782.
4. Lobstein T, Baur L, Uauy R; IASO International Obesity Task Force. Obesity in
children and young people: a crisis in public health. Obes Rev 2004; 1:4-10.
5. Smith SM, Craig LAC, Raja AE, et al. Growing up before growing out: secular
trends in height, weight and obesity in 56-year-old children born between 1970
and 2006. Arch Child 2013; 98:269-73.
6. Chinn S, Rona RJ. Prevalence and trends in overweight and obesity in three cross
sectional studies of British children, 197494. Brit Med J 2001; 322:246.
7. National High Blood Pressure Education Program Working Group on High
Blood Pressure in Children and Adolescents. The fourth report on the diagnosis,
evaluation, and treatment of high blood pressure in children and adolescents.
Pediatrics 2004; 114:555-76.
8. Kahn R, Buse J, Ferrannini E, Stern M, et al The metabolic syndrome: time for
a critical appraisal: joint statement from the American Diabetes Association
and the European Association for the Study of Diabetes. Diabetes Care 2005;
28:2289304.
104
6.
6.4. :

-

(1, 2).
, , LDL , ,
(1, 2).
1953. .
(3). 430. .

. 1920. . .
1930. , 1970. . ,
,
.
, ,
(, , )
(, , ) (1, 2). - ,
, ,
.
,
, ,
. , ,
, , ,
. ,
, (1).
. , (Tabela 1) (4).
105
1. (gr%)
()
3,1-15,6
3,7-10,6
1,0-2,5
1,1-1,8
12,5-65%.
4-6 , .
.
, .
, 1-2 . 5 gr, 1 gr (5).

. , , .
(1).
, , , , ,
, , , .
,
.
, .
, e ,
. , , (6). , , ,
, , .
, , , C
, (1).
,
, . , ,
,
. , ,

106
6.
(1). . ,
, , ,
, ,
(7, 8). , (7-9).
, , .
, . , ,
, , ,
(9).

, , ,
.
,
e e e
. , ,
, .
1. Slavin J. Fiber and prebiotics: mechanisms and health benefits. Nutrients 2013;
5:1417-35.
2. Rhoads BD, Levitsky LL. In: Duggan C, Watkins JB, Walker AW, editors. Nutrition
in Pediatrics. BC Decker Inc, Hamilton, 2008; 41-7.
3. Slavin JL. Dietary fiber: Classification, chemical analyses, and food sources. J Am
Diet Assoc 1987; 87:116471.
4. Ministry of AFF (UK). Manual of Nutrition, 1995. Nutrient Database for Standard
Reference (USA), 2005.
5. Committee on Nutrition, American Academy of Pediatrics. Carbohydrate and
dietary fiber. In: Kleinman RE, editor. Pediatric nutrition handbook, 6th edition.
American Academy of Pediatrics, Elk Grove illage, 2009; 343-56.
6. Wanders A, van den Borne JJ, de Graf C, et al. Effects of dietary fibre on subjective
appetite, energy intake and body weight: a systematic review of randomized
controlled trials. Obes Rev 2011; 12:724-39.
7. Ewaschuk JB, Dieleman LA. Probiotics and prebiotics in chronic inflammatory
bowel diseases. World J Gastroenterol 2006; 12:594150.
107
8. os AP, MRabet L, Stahl B, et al. Immunemodulatory effects and potential

working mechanisms of orally applied nondigestible carbohydrates. Crit Rev
Immunol 2007; 27:97140.
9. Anderson JW, Baird P, Davis RH Jr, et al. Health benefits of dietary fiber. Nutr Rev
2009; 67:188205.
108
7.
:
.
:
.
7.
7.1. A A

,

, . Treitz.
( 1). , , .
, ,
,
. , (, , ) (, ,
).
, ,
.
,
.
90%
, Treitz
(1). (haematemesis), (melena) (, ) (haematohesia).
, .
. ,
. ,

,
.
111
1.

Meckel
Meckel
HenochSchnlein
.
GERD
NEC
HUS
HUS
UC Mb. Crohn
. .
NEC: ; HUS: - ; GERD:

; UC:
, , , . , ,
, (, , ), ( ,
, ), .
, .

, , , , 32 .

,
. , , (2).
,
.
/ H2 ,
112
7.
(3). , , (, , ,
).
,
.
, (4).

.
(band ligation) , SengstakenBlakemore .

, . (- , Henoch
Schnlein ), - , HenochSchnlein .
. -
. ,
.
.
, , band
.
,
Meckel (5).
.
1. 2. , .
, . , a , je
. Meckel
, e
. Meckel . 99 . ,
, ,
.
113
1. Cadranel S, Scaillon M. Approach to gastrointestinal bleeding. In: Guandalini

S, editor. Textbook of Pediatric Gastroenterology and Nutrition. 2 ed. Taylor &
Frans, London, 2005; 639-54.
2. Kamath B, Mamula P. Gastrointestinal bleeding. In: Liacouras C, Piccoli D, editors:
Pediatric Gastroenterology: the Requisites in Pediatrics. Mosby,Philadelphia,
2007; 87-97.
3. Mamula P, Sreedharan R, Brown K. Gastrointestinal diseases. In: Shah S, editor:
PediatricInfectious Diseases. Blackwell Publishing, Malden, 2004; 79-89.
4. Kay M, Wylle R. Gastrointestinal hemorrhage. In: Wylle R, Hyams S, editors:
Pediatric Gastroenterology and Liver disease. Saunders Elsevier, Philadelphia,
2006; 203-15.
5. Wyllie R. Meckel diverticulitis. In: Kleigman RM, Stanton BF, Schol NF, editors.
Nelson Textbook of Pediatrics, 19th edition. Elsevier, Philadelphia, 2011; 1236-7.
114
7.
7.2.
, ,

, , .
, . ,
, .
Protosoe
Giardia lamblia , 30%.
. ()
.
, . ,
(, .). 1-2 ,
.
( 90% ), , , , ,
.
,
.(1).
, .
, ELISA .
metronidazola (flagyl, orvagyl), 5-10 mg/kg , 3 x , 50
mg 10 , 30 mg/kg 3 . timidazole
(fasigyn) 50 mg/kg nitazoxanide, 1-3 . 100 mg/12 h
3 , u 4-11 . 200 mg/12 h.

Cryptosporidium spp. .
.
1-7 ,
, , .
115
, ,
(IDS) , .(2). , ,
.
,
, .
Entamoeba hystolitica
500.000.000, 75.000
. ,
(3). ()
. - . , -
. 80-90% ,
, ,
. ,
, , .
,
,
, .
, ,
IgG .
metronidazol 50 mg/kg/24 h 10 diloksanid furoat 20 mg/kg/24h 10
. metronidazolom 50 mg/kg/24 h 10 , a a diloksanid furoata 20 mg/kg/24 h 10 .
Nematode
Trichinella spiralis .
( , , , , , .).
. , 5-7

(, , , .) . , . . (2-7
) , , , ,
.
116
7.
, , , ,
, , . . , .
90%.
,
m.tricepsa.
ELISA . (4). , , , , .
(
, , .)
( 1 h/kg).
, .
Ascaris lumbricoides
15-40 m. a 5%
15-30% .
, .
,
,
, .
2-3 , .
,

- . Lofflerov , (40 ), . Charcot-Leydenovi .

.
, (5).
, , . , .
,
,
.
, . mebendasola (vermox) 100 mg/24h,
, . tiabendazol (mintezol)
.
e .
117
, ,
richuris trichiura 90%. , ,

. 30-50 mm,
5.000 , . 2-3 .
. ,
(6). ,
- , , ,
.
, . mebendazola (vermox) 100 mg/24
h, 1 ,
.
Enterobius vermicularis .
, .

.
(7).
, , ,
. .
,
(8). mebendazol (vermox) 100 mg/24h.
. 10 .
pirantel pamoat piperazin. .
Cestode
nia saginata (). . 5-10
, () 4
.
,
. () ( ),
118
7.
().
(9).
, , , .
, .
. niklosamid (yomesan) 1.000
mg (1 gr) 10-35 kg, 1,5 gr 35 kg. ,
. praziquantela 10
mg/kg , paromomycina mebendazola.
Taenia solium, .
3 . , 1.000 .
.
- , . .
,
, , , , ,
. ,
,
, .
. ELISA,
CT . niklosamid (yomesan),
. CNS-a prasiquantelom 15 mg/kg ,
10 , .
1. Morrison HG, Mc Arthur AG, Gillin FD, et al. Genomic minimalismin the earli
diverning intestinal parasite Giardia lamblia. Science 2007; 317:1921-6.
2. Feigin RD, Cherry JD. Textbook of Pediatric Infectious Diseases. WB Saunders,
Philadelphia,1992.
3. Boinovi D. Paraziti debelog crijeva. U: Pavii A, urednik. Pedijatrijska
gastroenterologija. Naklada Ljevak, Zagreb, 2002; 249-50.
4. Kolata G. Testing for trichinosis: A new serological test should make it quick and
easy to detect trichomonas in meat - a fact of no small economic importance.
Science 1985; 227:621.
5. Boinovi D. Parazitarne crijevne infekcije. U: Pavii A, urednik. Pedijatrijska
gastroenterologija. Naklada Ljevak, Zagreb, 2002; 248.
6. Bethony J, Brooker S, Alhonico M, et al. Soil transmited helminth infections:
ascariasis, trichuriasis and hookworm. Lancet 2006; 367:1521-32.
119
, ,
7. Harhay M O, Horton J, Olliaro PL. et al. Epidemiology and control of human

gastrointestinal parasites in children. Expert Rev Anti Infect Ther 2010; 8:219-34.
8. Cook GC. Enterobius vermicularis infection. Gut 1994; 35:1159-62.
9. Mayta H, Talley A, Gilman RH, et al. Differentiating Taenia solium and Taenia
saginata infections by simple hematoxylin - eosin staining and PCR-restriction
enzyme analysis. J Clin Micobiol 2000; 38: 133-7.
120
7.
7.3.

, ,
, . , ,

: () .
() ,
, ,
, - , (1)
. (3). 6 , 10 30 ,
(2,5-3:1). .
.
(
HLA , HLA-B8, DR3 DR4) (2). CD4 T
,
B . -6, -8
- - . ,
Ebstein - Barrovim , -
, . 20%
. (NA)
a (S - antismooth muscle antibodies) . (LKM - liver-kidney microsomal
antibodies) a
(SLA-antibodies against soluble liver antigens)
, (2).
6 .
- .
121
. , ,
-.
(4). ,
.
(1, 2).
1 , N SMA
IgG. , 25% . 2 . LKM
1 , .
1.
. 2-5% . - .
,
, 1-, Wilsonove
(2,4) AST ALT, , GGT, .
, , .
,

. .
. .

10- 10%.
- 80% 5 .

10- 80%. HLA
DR3 , ,
.
. - (2). 1-2 mg/kg ( 60 mg/),
5 mg . 1 mg/kg/ , 1 mg/kg/
3 , (5 mg/)
122
7.
(2 - 3 mg/kg).
2 , ( 2,5 mg/, 25 mg/) . ,
( , , , ,
, ). ,
, . , , .
, , 65%
2- .
. , .
, , 6-, 6- (2)
, .
() ,
,
.Overlap sindrom

(2, 5).
. ,
. 2:1 . 80% (3).
50% ,
, , . , , AST ALT 2-3
IgG 60% . pANCA (90%), ANA ( 70%)
SMA ( 80%). . ANA SMA
PSH - AIH overlap sindrom (3). AST/ALT, ANA / SMA, IgG ,
PSH - AIH overlap sindrom.
( , gama GT ),
( )
MRCP ERCP,
123
(3).
overlap sindroma PSH AIH .
(UDHK) 1520 mg/kg/ . . .
.
A , , .
. AI , .
1. Mieli-Vergani G, Heller S, Jara P, et al. Autoimmune hepatitis. J Pediatr

Gastroenterol Nutr2009; 49:15864.
2. Manns PM, Czaja JA, Gorham DJ, et al. Diagnosis and management of autoimmune
hepatitis. AASLD practice guidelines. Hepatology 2010; 51:1-31.
3. EASL Clinical Practice Guidelines: management of cholestatic liver diseases.
European Association for the Study of the Liver. J Hepatol 2009; 51: 23767.
4. Gregorio GV, Portman B, Reid F, et al. Autoimmune hepatitis in childhood: a 20year experience. Hepatology 1997;25:541-7.
5. Gregorio GV, Portmann B, Karani J, et al. Autoimmune hepatitis/sclerosing
cholangitis overlap syndrome in childhood: a 16-year prospective study.
Hepatology 2001;33:544-53.
124
7.
7.4.

,
,
, ,
,
. ,
, , (1).
, , . ,
. , . ,
.

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

. , -
.

(3-5 mm), .
125
. (C2) .

. , .
(rendezvous) . ( ) . .

, ,
. ,
.
(5).
.
(6).

,
, ,
(7).
- , .
, . ,
.
, (8).
, (9).
- , , ,

( ). , .
.
, -
(10).
126
7.
1.
(. - , . 15/90 . - , . 4/96 2/97).
2. Oyama T, Kikuchi Y. Aggressive endoscopic mucosal resection in the upper GI
tractHook knife EMR method. Min Invas Ther Allied Technol 2002; 11:2915.
3. Gotoda T, Kondo H, Ono H, et al. A new endoscopic mucosal resection procedure
using an insulation-tipped electrosurgical knife for rectal flat lesions: report of
two cases. Gastrointest Endosc 1999; 50:5603.
4. Ono H, Kondo H, Gotoda T, et al. Endoscopic mucosal resection for treatment of
early gastric cancer. GUT 2001; 48:2259.
5. Rosch T, Sarbia M, Schumacher B, et al. Attempted endoscopic en bloc resection
of mucosal and submucosal tumors using insulated-tip knives: a pilot series.
Endoscopy 2004; 36:788801.
6. Sebastian MW. Benign tumors of the stomach. In: Sabiston DC, editor: Textbook
of Surgery, 15th ed. WB Saunders, Philadelphia, 1997; 86970.
7. Bax NM. Laparoscopic surgery in infants and children. Eur J Pediatr Surg 2005;
15:31924.
8. Siewert JR. Operation, intervention, rendezvous-manoever. Chirurg 2000;
71:1191-2.
9. Gurbuz AT, Peetz ME. Resection of the gastric leiomyoma using combined
laparoscopic and gastroscopic approach. Surg Endosc 1997; 11:285-6.
10. Trias M, Targarona EM, Balague C. Endoscopically assisted laparoscopic partial
gastric resection for treatment of a large benign gastric adenoma. Surg Endosc
1996; 10:3446.
127
8.
:
.
:
.
8.
8.1.

.
,
, ,

, . , ,
.
, (< 3 ), ( 3-8 ),
(> 8 ). ,
( 3-12 ) (1).
, .
, . , , .

, .

. ,
, . , . .

, , , . ,
,

() (high resolution CT HRCT) (2). ,
, .
131
,
,
() (chronic suppurative lung disease CSLD).
, .
, ,
() (persistent bacterial bronchitis).
, .
,
, ,
(3). ,

(4).
. ,
, . , :
,
. ,

(5).

,
.

.

. ,
,
(, , )
(2). . , ,
, , .
,
, , . () (6,7).
,
132
8.
. , . ,
,
, .
1. Marchant JM, Masters IB, Taylor SM, et al. Evaluation and outcome of young
children with chronic cough. Chest 2006; 129:1132-41.
2. Douros K, Alexopoulou E, Nicopoulou A, et al. Bronchoscopic and highresolution CT scan findings in children with chronic wet cough. Chest 2011;
140:317-23.
3. Chang AB, Redding GJ, Everard ML. Chronic wet cough: protracted bronchitis,
chronic suppurative lung disease and bronchiectasis. Pediatr Pulmon 2008;
43:519-31.
4. Donnelly D, Critchlow A, Everard ML. Outcomes in children treated for persistent
bacterial bronchitis. Thorax 2007; 62:80-4.
5. Everard M. Recurrent lower respiratory tract infections: going around in circles,
respiratory medicine style. Pediatr Respir Rev 2012; 13:139-43.
6. Priftis K, Litt D, Manglani S, et al. Streptococcus pneumoniae and non-typable
Haemophilus influenzae causingbacterial bronchitis in children and the impact
of vaccination. Chest 2013; 143:152-7.
7. Priftis KN, Mermiri D, Papadopoulou A, et al. The role of timely intervention in
middle lobe syndrome in children. Chest 2005; 128:2504-10.
(: )
133
Kostas N. Priftis
8.1. EVALUATION AND OUTCOME OF CHRONIC WET

COUGH IN CHILDREN
Kostas N. Priftis
Paediatric Respiratory and Allergy Unit, 3rd Dpt of Paediatrics of Athens University,
Attikon University Hospital, Athens, Greece
Introduction definitions
Cough is a protective reflex that serves to clear the airways from excessive secretions, debris and aspirated material. It is a common albeit non-specific symptom
of respiratory disease in children.
According to its duration cough can be classified as acute (<3 weeks), prolonged
acute or subacute (3-8 weeks), and chronic (>8 weeks). However, the definition of
chronic (or persistent) cough by different authors ranges from 3 to 12 weeks.
Cough quality, specifically dry versus wet or productive cough, is often used. In
adults, productive cough is usually obvious but children often swallow their sputum
and hence a wet is used inter-changeably with productive to describe cough quality
in young children who are unable to expectorate.
The sound of a cough is due to vibration of larger airways and laryngeal structures during turbulent flow in expiration. It has been shown that cough quality of
wet/dry generally relates to bronchoscopic secretions. When cough is wet, secretions
are always present whereas when cough is dry secretions if present, are usually minimal or mild.
Chronic wet cough is common in the paediatric population, yet the true prevalence of this condition has not been well established, in part due to variations in the
definition.
Protracted Bacterial Bronchitis and Bronchiectasis

Chronic wet cough strongly suggests endobronchial infection which, if left untreated, may progress to established bronchiectasis.
Bronchiectasis is a well-defined term, especially in the adult medical literature. Its
diagnosis is currently based on high-resolution CT (HRCT) scan findings, although
the adult radiologic criteria may not always be suitable for children. The term chronic
suppurative lung disease (CSLD) is used to describe a diagnosis with clinical symptoms
similar to those of bronchiectasis but without the characteristic HRCT scan findings.
The main symptom in both conditions is the excessive prolongation of wet cough. A
similar but milder condition, which is termed protracted bacterial bronchitis (PBB),
134
8.
is defined as isolated long-term wet cough, which resolves with antibiotic treatment,
in the absence of alternative etiology. These three conditions bronchiectasis, CSLD,
and PBBmay not be different entities but more likely represent the wide spectrum of
chronic airway infection, which, if left untreated, may progress from PBB to CSLD and,
finally, to radiologically evident bronchiectasis.
It is likely that many of the patients with asthma that have chronic wet cough
are treated as asthmatics although they are not. PBB causes persistent coughing and
disturbed sleep, and may affect exercise tolerance, causing significant levels of morbidity. PBB has remained largely unrecognised. Its diagnosis is not readily accepted
by pediatricians.
Other rare conditions, e.g. Cystic Fibrosis, Primary Ciliary Dyskinesia or immunodeficiency frequently present with chronic wet cough, but the most common
causes have not been determined on a population level.
Chronic wet cough evaluation

History and physical examination are of utmost importance because they provide
guidance in order to customize the investigation, which can become unnecessarily
exhaustive. Careful evaluation of the specific characteristics and knowledge of the
differential diagnosis are of essence.
Chest radiographs are often normal or may have only minor abnormalities such
as peribronchial wall thickening. Currently bronchiectasis defined by irreversible
dilatation of peripheral airways, is usually diagnostically established radiologically
by chest HRCT scans.
Cough swabs can be useful but have a relatively low sensitivity. The definitive investigation is fibreoptic bronchoscopy with BAL, although care is needed when interpreting results. In most with relatively minor changes of bronchiectasis the changes
are reversible while the danger of a normal CT is that the child is not given aggressive treatment.
Research is required to improve diagnosis, particularly in the earliest stages, and
to try and improve our understanding of how to optimize treatment while minimizing the use of antibiotics. May be the key intervention is to couple reduced antibiotic
prescribing for viral infections in primary care with awareness that a persistent cough
lasting longer than say 3 weeks might require oral antibiotics, not forgetting the possibility of asthma.
135
8.2.
,

,
,
() ,
(),
- .
4-5%, 2500-4000
.
, (1: 18000) (1: 31000) .
, ,
1:3500 .
. 1940. 1964.
20% , 10%.
37,8 ,
31 (1).
.
(250 ) ( . Cystic
fibrosis transmembrane regulator) , ,
.
,
, (Cl-)
, , , .
, ,
(Na+) , (NaC). ,
Na+ . Cl Na+
,
136
8.
. , . ,
( ). ,
,
( 1) (2).
1. .
. . : ,
,
.
.

.
.

, -8,
. , , .
,
(3).

508 (F508 F508del)
1480 (4).
, F508
70% , . ,
, 1900 .
137
( 2).
2. . : . I:
. II: . III: .
IV: . V: . VI
( ): .
I ( , G542X) (mRNK) , . II ,
F508, ,
, ,
, , .

trafficking- (. traffic- ). III
( G551D),
IV ( R117). III
gating- (. gat - , ). V
( ) mRNK,
. VI
je .
I, II III ,
.
I, II III . ,
IV V , , IV V .
,

(2).
138
8.

:
( ) , (5).

() .
.
.
, ,
. ,
.

.
GL67, . , ,
- .
. ,
.
,
GL67 (6).

.
.
.
: , - (7).
139
-

- . , 5-10%
I. -
-
. , .
, .
, PTC124 , .

(6).

. II,
- F508del.
VX-809 IIb
F508del . , , .
VX-809
(7).

- gating ( III) ,
( IV ).
Ivacaftor, VX-770,
III G551D
.
. FEV1,
,
50% (8).
140
8.
1. Cystic Fibrosis Foundation. Patient registry: Annual data report 2010. Bethesda,
MD: Cystic Fibrosis Foundation; 2011.
2. Ratjen F, Dring G. Cystic fibrosis. Lancet 2003; 361:681-9.
3. Tiddens HA, Rosenfeld M. Cystic fibrosis. Respiratory manifestations. In:Taussig
LM, Landau LI (editors). Pediatric Respiratory Medicine, 2nd ed. Mosby,
Maryland, 2008; 871-87.
4. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis
gene: genetic analysis. Science 1989; 245:107380.
5. Elborn SJ. Personalised medicine for cystic fibrosis: treating thebasic defect. Eur
Respir Rev 2013; 22:35.
6. Rogan MP, Stoltz DA, Hornick DB. Cystic fibrosis transmembrane conductance
regulator intracellular processing, trafficking, and opportunities for mutationspecific treatment. Chest 2011; 139:148090.
7. Clancy JP, Jain M. Personalized medicine in cystic fibrosis: dawning of a new era.
Am J Respir Crit Care Med 2012; 186: 5937.
8. Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with
cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365:166372.
141
8.3.

,
,
. . , (T 1).
, ( , , ), .
1.
Wheezing
Ig,
FeNO
Ig,
FeNO
IgE,
,
LT, FeNO
IgE,
FeNO
,
-2 ,
: FeNO , ,
LT -
( ) . . Ltvall (1) : -, ,
,
, . Wenzel :
, ,
, (2).
142
8.
,
. -IgE
(omalizumab)
IL-4 IL-13 (3). IL-13 (lebrikizumab)
.
. IL-13 (4). IL-5 (mepolizumab) ,
(5).
(6).

.
1. Ltvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach
to classification of disease entities within the asthma syndrome. J Allergy Clin
Immunol 2011; 127:355-60.
2. Wenzel SE. Complex phenotypes in asthma: current definitions. Pulm Pharmacol
Ther 2013; 26:710-5.
3. Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with antiimmunoglobulin E antibody (omalizumab). Pediatrics 2001; 108:E36.
4. Vijverberg SJ, Koenderman L, Koster ES, et al. Biomarkers of therapy responsiveness
in asthma: pitfalls and promises. Clin Exp Allergy 2011; 41:615-29.
5. Poon AH, Hamid Q. Asthma endotypes: the right direction towards personalized
medicine for asthma. Asthma Endotypes. Expert Rev Clin Immunol2012; 8:595-6.
6. Calkan M, Bochkov YA, Kreiner-Mller E, et al. Rhinovirus wheezing illness and
genetic risk of childhood-onset asthma. N Engl J Med 2013; 11; 368:1398-407.
143
8.4.
?

,
eudemonia
, , , ,
.
,,
. : , , ,
(1).
()
,
.
HRQoL (Health Related Quality of Life)
() , , ,
, , , (2).

.

(Qual Life Res; Value Health; J Adolesc Health; Health Qual Life
Outcomes) .
,
. 4 :
, , . ,
: , , , , , . , .
( ) .

.
144
8.
(Child Health Qestionnaire CHQ).

. , .

, , , (3).
, , ,
, . ,
, .
.
, , .
, ,
.
, (), ,
.
, .
. , ,
, ,
.
- . , , , ,
,
, . ,
, .
,

.
, ,
.

, /.

145
(Pediatric Asthma Quality of Life Questionnare PAQLQ)

/ (Pediatric Asthma Caregivers Quality of Life Questionnare
PACQLQ) 1994. . Elizabeth F. Juniper, . (Mini Pediatric
Asthma Quality of Life Questionnare M - PAQLQ)
(3).
1994. Juniper
.
.
,
.
, Quality of Life Research (Qual Life Res)
.

, Roncada (2013) 0 18 , 2301 19902012 PubMed, 162 . 15
: (Childhood Asthma QuestionnaireCAQ);
(Childhood Asthma Control Test C ACT ); (Disability Kids DISABKIDS) PAQLQ (4).
?

.
,
, .
(4-11 ) Asthma Control
Test (ACT) Childhood Asthma Control Test (c-ACT)
Pictured Childs Quality of Life Self Questionnaire for the children
PACQLQ. ,
(ASUI),
.
12 AQLQ(S)12+ 12 .
, , 18 14, 2
PAQLQ.
146
8.
.
7 17 . 23 3 :
- : 10 (, ,
);
- : 5 (, ,
);
- : 8 (, , , ).

1 7, 1 , 7
.
/ (PACQLQ) 13
2 :
- , : 4 : ,
,
- : 9 : , , , ,
.
( ) /
1 7, 1 , a 7 .
( / ). , ( 1 7). ,
(,
) .
, ( ) .

,
.
, .
, 0,5 (), . ;
1,0 2,0 , 2,0
.
147

( ),
( ), (
- ), ( - ),
, , .
, , (5).
,
: , (-2429 USA),
(6,7).
. ()
, .
(), 2 (),
( + ; + ) ,
( , , ) (8).
/
.
( ).
.
, , (9,10).
7-17 ,
,
.
.

(11).
, ,
.
, , .
148
8.
1. Bullinger M, Anderson R, Cella D. Developing and evaluating cross cultural

instruments form minimum recuirements to optimal models. Qual Life Res
1993; 2:451-9.
2. WHOQOL Group. Mesauring Quality of Life: The Development of the World Health
Organisation Qulatity of Life Instrument (WHOQOL) WHO, Geneva, 1993.
3. Wilson IB, Cleary PD. Linking clinical variables with health related quality of life;
a conceptual model of patient outcomes. JAMA 1995; 273:59-65.
4. Juniper EF. How important is quality of life in pediatric asthma? Pediatr Pulmonol
Suppl 1997; 15:17-21.
5. Roncada C, Mattiello R, Pitrez PM, Sarria EE. Specific instruments to assess
quality of life in children and adolescents with asthma. J Pediatr (Rio J) 2013;
89:21725.
6. Singh M, Mathew JL, Malhi P, et al. Comparison of improvement in quality of life
score with objectiv parameters of pulmonary function in Indian asthmatic children
receiving inhaled corticosteroid therapy. Indian Pediatr 2004; 41:1143-7.
7. Petsios KT, Priftis KN, Hatziagorou E. Determinants of quality of life in children
with asthma. Pediatr Pulmonol 2013; 48:117180.
8. Stanford RH, GilsenanAW, Ziemiecki R, et al. Predictors of uncontroled asthma
in adult and pediatric patients: analysis of the Asthma Control Characteristics
and Prevalence Survey Studies (ACCESS). J Asthma 2010; 47:257-62.
9. Guilbert TW, Garris C, Jhingran P, et al. Asthma that is not well-controlled is
associated with increased healthcare utilizationand decreased quality of life. J
Asthma 2011; 48:126-32.
10. Halterman JS, Yoos HL, Conn KM, et al. The impact of childhood asthma on
parental quality of life. J Asthma 2004; 41:645-9.
11. Kosti G. Procena kvaliteta ivota kod dece obolele od astme pre i posle
terapije inhalacionim glikokortikoidima. Doktorska disertacija, Univerzitet u
Kragujevcu; 2009.
149
, ,
8.5.

, ,

,
e () ,
, - . - ,
, ,
, ,
(1,2).
,
, (3).

.

. ,
(4).

. 1.
150
8.
1.

( )

,

(5).
.

, .

.
( ), , , , ,
. 2.
151
, ,
2.

(, , )

, .
, .
1. Palange P, Ward S, Carlsen K-H, et al. Recommendations on the use of exercise

testing in clinical practice. Eur Respir J 2007; 29:185-209.
2. Karila C, de Blic J, Waernessyckle S, et al. Cardiopulmonary exercise testing in
children: An individualized protocol for workload increase. Chest 2001; 120:81-7.
3. Wasserman K, Hansen J, Sue D, et al. Principles of Exercise Testing and
Interpreatation, Lippincott Williams & Wilkins, Philadelphia, 2005.
4. Sovti A, Mini P, Rodi M, i sar. Uloga ergospirometrije u dijagnozi i praenju
oboljenja respiratornog sistema. U: Zdravkovi D (ured): Problemi u pedijatriji
2011, Zavod za udbenike i nastavna sredstva, Beograd, 2012; 407-18.
5. Sovtic A, Minic P, Kosutic J, et al. Static hyperinflation is associated with decreased
exercise performance in children with cystic fibrosis. Respir Care 2013; 58:2917.
152
9.
:
.
:
.
9.
9.1.

,
,
() .

, .

. ( ),
,
.
()
(), .
( j,
/ ) , ,
. , .
,
.

.
,
, / . (1).

,
(2). , ,
,
.
.
155
,
(3). ,
(49%) 2 (4).
890 , 16. (P16)
55%, 52% , 7% P 3
. , P5 je 65%
, 41% .
63% .
,
- (5).
(1).
:
1. ( , ) (, );
2. , .
( , , , , );
3. (, , , );
4. (, , e );
5. ( , ,
);
6.
, .
(Tetralogia Fallot,
) (6).
(. )

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

, .
()
156
9.
, ,
.
, ,
. .
(7).
,
.
, 120 ml/kg/
, 150 ml/kg/ .
( ), / . 4
( o ), ,
. ,
,
.
, Sy Down Turner, , .

. : ,
. 1/3
48 -
.
. e . ,
.

/ ,

. (8)
157

, .
,
,
. .
, , ,
e
7. , ,
6 12 (9).

, ,
.

.
,
.
.
,
.
1. Palinski W and Napoli C. Impaired Fetal Growth, Cardiovascular Disease, and

the Need to Move on. Circulation. 2008;117:341-343.
2. Nydegger A, Bines JE. Energy metabolism in infants with congenital heart disease.
Nutrition 2006; 22:697704.
3. Huse DM, Feldt RH, Nelson RA, et al. Infants with congenital heart disease: food
intake, body weight, and energy metabolism. Am J Dis Child 1975; 129:659.
4. Thommessen M, Heiberg A, Kase BF. Feeding problems in children with
congenital heart disease: the impact on energy intake and growth outcome. Eur J
Clin Nutr 1992; 46:457 64.
158
9.
5. Varan B, Tokel K, Yilmaz G. Malnutrition and growth failure in cyanotic and

acyanotic ongenital heart disease with and without pulmonary hypertension.
Arch Dis Child 1999; 81:4952
6. Forchielli ML, McColl R, Walker WA, et al. Children with congenital heart
disease: a nutrition challenge. Nutr Rev 1994; 52:34853.
7. Mehrizi A, Drash A. Growth disturbance in congenital heart disease. J Pediatr
1962; 61:418 29.
8. Buheitel G, Scharf J, Dorr HG, Ramsauer T, Schuderer E, Singer H. Follow-up
of hormonal and metabolic parameters after heart operations in childhood [in
German]. Monatsschr Kinderheilkd 1993;141:42733.
9. Hansen SR, Dorup I. Energy and nutrient intakes in congenital heart disease.
Acta Paediatr 1993; 82:166 72.
159
9.2.

,
,
(), 3-9% , .
, >40% . 1-2/1000 . .
, ,
/
(1-4). ,
. (1,5/1000
) o,
30 (5). ,
115
.
. ()
(), -
( ), , ,
) - ( -, )).
, , . , ().
-
(). - 50% , 41%, 9%
- (4,6).
160
9.
, , , , , . , ,

25-30% . , , . , 75% -
60% -
. 30% -
38% (1-3,7).
, 7/100.000 0,42/100.000 .

, 80 94%, .
. 50%
.
(), , , , .
, (6,7,8).
, .
, . ,
, , ,
5 .

90- . , : , ,
,
.
55%
(7). , ,
e , , (8,9).
161
- ,
2012. (3). -
76,5%, 99,9% 0,14% .
, 76,5%
-
, , (3).

,
, . , , (
) 3-5 . 24
, , .
(). ,
90-95%, 1 , 95%
. < 95%
. < 90%
.
> 95% (2,6,7,8).
1.
.
24 48 .
<90%

90-95%

>3%

95%

3%

<90%

90-95%

>3%

95%

3%

<90%

162
90-95%

>3%

95%

3%

9.

( ) < 95%. , . 24
.
,
0,05-0,1%.
,
.

(2,3,6-8).

95% .
1:10.000 . -
-, , ,
95%. ,
.
38.429 , , 28/100 .
11/25 (44%) 5
. ,
5/60 (8%) (2,7).
. () < 0,70,
, . ,

(10).
163

. 25-30
.
.
1. Mellander M. Diagnosis and management of life-threatening cardiac malformations in the newborn. Semin Fetal Neonat Med 2013; 18:302-10.
2. Frank HL, Bradshaw E, Beekman R, et al. Critical Congenital Heart Disease
Screening Using Pulse Oximetry. JPEDS 2013; 162:445-53.
3. Thangaratinam S, Brown K, Zamora J, et al. Pulse oximetry screening for critical
congenital heart defects in asymptomatic newborn babies: a systematic review
and meta-analysis. Lancet 2012; 379:2459-64.
4. Mellander M, Sunnegardh J. Failure to diagnose critical heart malformations in
newborn before discharge an increasing problem? Acta Paediatr 2006; 95:407-13.
5. Heron M. Deaths: final data for 2006. National vital statistics reports. US CDC
2009; 57(14).
6. Kemper RA, Mahle W, Martin RG, et al. Strategies for implementing screening
for critical congenital heart disease. Pediatrics 2011; 128:1260-7.
7. Hoffman IEJ. It is time for routine neonatal screening by pulse oximtery.
Neonatalogy 2011; 991-9.
8. Mahle TW, Newburger WJ, Matherne GP, et al. Role of pulse oximetry in
examining newborns for congenital heart disease: a scientific statement from the
AHA and AAP. Pediatrics 2009; 124:823-36.
9. Mahle TW, Martin RG, Beekman HR, et al. Endorsement of health and human
services recommendation for pulse oximetry screening for critical congenital
heart disease. Pediatrics 2012; 129:190-2.
10. Granelli AdW, Ostman-Smith I. Noninvasive peripheral perfusion index as a
possible tool for screening for critical left heart obstruction. Acta Paediatr 2007;
96:1455-9.
164
9.
9.3.

,
,
() . () 100/ , 24
- 95/ .
,
, , , , .
1979. (1) 15-50 . .

16
.
, .
,
,

.
(2).
165
, funny current ili If (3).

, If ,
. If
.
If (Hcn 1-4) .
4 , Hcn 4
. Hcn 4
.
If
. If
.
, / . , ( 1). Chiale
(4) --
( 11/21 )
.
1.

, ()
(T 2).
, . Marrouche
(5), 100% (,
, , ) (5).
166
9.
2.

, , , ,

EK- 24 -.
. , . ,
2, (6).
()
(). ,
-. -
30 120
10 ,
.

, .

. . ,
.
167
,
. , ,
.
(, , , , , , )
.
, . ,

.
If
, Hcn
. , Hcn , . Cappato (7)
6 ,
.

75 % , 24
.
,
. ,
. ,

,
(8).

(9). Lee (10) 16
, 2 pacemakera:

. ,
. ,
pacemakera.
168
9.
1. Bauernfeind RA, Amat-Y-Leon F, Dhingra RC, et al. Chronic nonparoxysmal sinus

tachycardia in otherwise healthy persons. Ann Intern Med 1979; 91:70210.
2. Lakatta E, Di Francesco D. What keeps us ticking: a funny current, a calcium
clock, or both? J Mol Cell Cardiol 2009; 47:15770.
3. Di Francesco D. The role of the funny current in pacemaker activity. Circ Res
2010; 106:43446.
4. Chiale PA, Garro HA, Schmidberg J, et al. Inappropriate sinus tachycardia may be
related to an immunologic disorder involving cardiac beta andrenergic receptors.
Heart Rhythm 2006; 3:1182 6.
5. Marrouche NF, Beheiry S, Tomassoni G, et al. Three-dimensional nonfluoroscopic
mapping and ablation of inappropriate sinus tachycardia. Procedural strategies
and long-term outcome. J Am Coll Cardiol 2002; 39:1046 54.
6. Olshansky B, Sullivan R. Inappropriate sinus tachycardia. J Am Coll Cardiol
2013; 61:793801.
7. Cappato R, Castelvecchio S, Ricci C, et al. Clinical efficacy of ivabradine in
patients with inappropriate sinus tachycardia: a prospective, randomized,
placebo-controlled, double-blind, crossover evaluation. J Am Coll Cardiol 2012;
60:13239.
8. Scheinman M, Vedantham V. Ivabradine: a Ray of Hope for Inappropriate Sinus
Tachycardia. J Am Coll Cardiol 2012; 60:13302.
9. Shen W. How to manage patients with inappropriate sinus tachycardia. Heart
Rhythm 2005; 9:1015-9.
10. Lee RJ, Kalman JM, Fitzpatrick AP, et al. Radiofrequency catheter modification of the
sinus node for inappropriate sinus tachycardia. Circulation 1995; 92:2919 28.
169
9.4.

,
,
() . (1).

.
,
.
3% . , 45% ,
, . 35% , 37%
, 42% 48% (2).

,
.
.
(2).

.
, 35% 43%
15% (3).

, (),
(), ()
().
6-8 . ,
50% (4). ,
99,8% (2%).
170
9.
,
. , 15%
1990. 5% 2000. (5).
.
.

,
. .

,
.
4 85,9 1000 . ,
79 100, ( 28. ) 27,5, 73,2
1000 (1, 6). 2% ,
22%-43% , .
.
, . .
,
,
- 6 1000 (7).

.
,
. , . 1993. 1995.
171
( )
, .
3,7
17,5 1000, 30-45% ( 1) (6).
79,7 1000 (8). : ( , ),
.
1. ,
1000

Defectus septi ventriculorum
Ductus arteriosus persistens
Defectus septi atriorum
Cannalis atrioventricularis
communis
Atresia arteriae pulmonalis
Stenosis arteriae pulmonalis
Stenosis aortae
Coarctatio aortae
T.Fallot
Transpositio vasorum
magnum cordis
Hypoplasio ventriculi dextri
Hypoplasio ventriculi sinistri
Atresia valvulae tricuspidalis
Morbus Ebstein
Truncus arteriosus
DORV
Cor univentriculare
Connectio anomalia venarum
pulmonalium
Sve USM
Valvula bivelaris aortae
Hoffman i Kaplan,2002*
( /)
3.57 / 2.83
0.80 / 0.57
0.94 / 0.56
Reller, 2008*
(MACDP)
4.18
0.29
1.31
Dolk i Loane 2009**

(Eurocat)
3.06
--2.05
Wu, 2010*
(Azijati)
4.01
2.01
3.23
0.35 / 0.34
0.41
0.19
0.20
0.13 / 0.08
0.73 / 0.53
0.40 / 0.26
0.41 / 0.36
0.42 / 0.36
0.04
0.55
0.11
0.44
0.47
0.09
0.40
0.14
0.34
0.28
--1.22
0.16
0.25
0.63
0.32 / 0.30
0.23
0.35
0.21
0.22 / 0.16
0.27 / 0.27
0.08 / 0.09
0.11 / 0.04
0.11 / 0.09
0.16 / 0.13
0.11 / 0.09
--0.23
0.05
0.06
0.06
--0.10
0.04
0.26
0.08
0.05
0.09
--0.07
--0.06
0.05
0.05
0.08
0.15
---
0.09 / 0.09
0.08
0.05
0.11
9.60 / 7.67***
13.56/9.24
8.14
---
7.05
---
13.08
---
*
** ( , )
*** , ,
172
9.

.
,
, .
(18-25%) .

. .
4,9%
,
. ,
, .
,
,
.

. 2000. 150
000 , 11,500
(9).
8,8% 1000 , 8,500 (11).

. .
10% , , ,
, , .

, 90% .

. , 47%
(10).
.
173
1. Mitchell SC, Korones SB, Berendes HW. Congenital heart disease in 56,109 births.
Incidence and natural history. Circulation 1971; 43:323-32.
2. Botto LD, Correa A. Decreasing the burden of congenital heart anomalies: an
epidemiologic evaluation of risk factors and survival. Prog Pediatr Cardiol 2003;
18:11121.
3. Germanakis I, Sifakis S. The impact of fetal echocardiography on the prevalence
of liveborn congenital heart disease. Pediatr Cardiol 2006; 27:465-72.
4. Knowles R, Griebsch I, Dezateux C, et al. Newborn screening for congenital heart
defects: a systemic review and cost-effectiveness analysis. Health Technol Assess
2005; 9:1-6.
5. Kenny D. Long-term outcome of the child with congenital heart disease. Paediatr
Child Health 2008; 19:37-42.
6. Hoffman JIE, Christianson R. Congenital heart disease in a cohort of 15502 births
with long-term follow-up. Am J Cardiol 1978; 42:641-7.
7. Hoffman JIE, Kaplan S. The Incidence of Congenital Heart Disease. J Am Coll
Cardiol 2002; 39:1890-900.
8. Dadvand P, Rankin J, Shitley MDF, et al. Descriptive epidemiology of congenital
heart disease in Northern England. Paediatr Perinat Epidemiol 2008; 23:58-65.
9. Report of the British Cardiac Society Working Party. Grown-up congenital heart
(GUCH) disease: current needs and provision of service for adolescents and
adults with congenital heart disease in UK. Heart 2002; 88:i1-i4.
10. Reid GJ, Irvine MJ, McCrindle BW, et al. Prevalence and correlates of successful
transfer from pediatric to adult health care among a cohort of young adults with
complex congenital heart defects. Pediatrics 2004; 113: e197-e205.
11. Van der Bom T, Bouma BJ, Meijboom FJ, et al. The prevalence of adult congenital
heart disease, results from a systematic review and evidence based calculation.
Am Heart J 2012; 164:568-75.
174
10.
:
. -
:
.
10.
10.1.
-
,
,

()
1/400-1000
(1).
( ) ,
. .
(
). ,
.
20. 95%, 30. . , ,
.
, 5,3% (2).
, ,
(). ,
50% . (2-5%),
, ,
, .
- () (3).

(
, / ) , .
10% 9 .
(4).
,
, .
177
8%,
. ( 16%)

.
. , 30 (5). 20% , 75% .
. .
, . ,
.
( ) 1539 2
4059 . (60), 4
(6).
( 85%) PKD1 16p13.3, 15% PKD2 4q21

(7). PKD1 -1, PKD2 -2.
-1 -2 .
, , (8).
PKD1/PKD2
. : (1) 30
, (2) ,
(3)
(8). , PKD2 PKD1
15-20 (53 69 ) (7).
178
10.

()
.
1: 20,000 (7, 9). .
,
10 . ,
,
.

.
(7).

, 2-5% , . ,
, . . 30% 50%
.
/. .
80% , 50%
. .

, ,
.
,
. , . , , .
,
.
179
PKHD1 . PKHD1
(7).
/. 350 PKHD1 80% (8).
-1, -2, /, .
.
, ,
.

, , .
V2 (), (, -8050), ()
(c-myc EGFR ) (7, 8). - (I R ),
( n-3 ).

(8).
180
10.
in utero
, , .
( / ) ( )
.
, . .
1. Wilson PD. Polycystic kidney disease. N Engl J Med 2004; 350:151-64.

2. Grantham JJ, Torres VE, Chapman AB, et al. Volume progression in polycystic
kidney disease. N Engl J Med 2006; 354:2122-30.
3. Sedman A, Bell P, Manco-Johnson M, et al. Autosomal dominant polycystic
kidney disease in childhood: a longitudinal study. Kidney Int 1987; 31:1000-05.
4. Bear JC, McManamon P, Morgan J, et al. Age at clinical onset and at
ultrasonographic detection of adult polycystic kidney disease: data for genetic
counselling. Am J Med Genet 1984; 18:45-53.
5. Mariani L, Bianchetti MG, Schroth G, t al. Cerebral aneurysms in patients
with autosomal dominant polycystic kidney diseaseto screen, to clip, to coil?
Nephrol Dial Transplant 1999; 14:2319-22.
6. Bear JC, McManamon P, Morgan J, et al. Age at clinical onset and at
ultrasonographic detection of adult polycystic kidney disease: data for genetic
counselling. Am J Med Genet 1984; 18:45-53.
7. Torres VE,Harris PC. Autosomal dominant polycystic kidney disease: the last 3
years. Kidney Int 2009;76:149168.
8. Bergmann C, Zerres K. Polycystic Kidney Disease: ADPKD and ARPKD. In:
Geary DF, Schaefer F (eds): Comprenhensive Pediatric Nephrology, Mosby
Elsevier, Philadelphia 2008; 154-78.
9. Sweeney WE Jr, Avner ED. Molecular and cellular pathophysiology of autosomal
recessive polycystic kidney disease (ARPKD). Cell Tissue Res 2006; 326:671-85.
181
10.2.

,
(: ) - , , , . ().
12 70%
(1, 2).
. , . ,
.
.
, () .
, , ,
, . ,
(), . (2, 3).
1:50.000
. .
, ,
, .
, . ,
. .
( , , , ),
.
() , . , , ,
.
, (3, 4, 5).
182
10.
NFC2/, NFC 1, 4, 5, 6, 7, 8, 9, 11 NFC3. NPHP1

1, . 2 4
, NFC 2, 4, 6 . NF2/
, ,
, (4).
, ,
- , , , (5, 6).
,
. NFC5 6
,
.
NFC5 6, 10% NFC 1, 2, 3, 4.
NFC 1 4.
( )
, , , ,
, , . 20% . .
- -
, 9 , NFC3. , . , , ,
, ,
.
. , , , , ,
, , , . , . , .
- () . , , , , . 16
. , .
70%
, .
183

() , , ,
.
UC1 , , 1q21
1. .
2 , ,
16, /
. () . 2
(7). , .
.
,
, .
1. Salomon R, Saunier S, Niaudet P. Nephronophthisis. Pediatr Nephrol 2009;

24:2333-44.
2. Yoder B. Role of primary cilia in pathogenesis of polycystic kidney disease. J Am
Soc Nephrol 2007; 18:1381-88.
3. Dell KM. The spectrum of polycistic kidney disease in children. Adv Chronic
Kidney Dis 2011; 18:339-47.
4. rts HA, Knoers NVA. Current insights into renal ciliopathies, what can genetics
teach us. Pediatr Nephrol 2013; 28:863-7.
5. Wolf MT, Hildebrandt F. Nephronophthisis. Pediatr Nephrol 2011; 26:181-94.
6. Hildebrandt F, Zhou W. Nephronophtisis associated ciliopathies. J Am Soc
Nephrol 2007; 18:1855-71.
7. Hurd T, Hildebrandt F. Machanisms of nephronophthisis and related ciliopathies.
Nephron Exp Nephrol 2011; 118:e9-14.
184
10.
10.3. -

, -
, , ,
,
, .
,
. ,
, , .
9 , (1).
. ,
(). ,
(ATP). . , , - .
9
. ,
().
, , ,
( ).
,
(1, 2).
, . , , .
(3). , , ,
( , ) ,
(4). .
(Joubert , Caroli , MeckelGruber , SeniorLken , 1, ,
185
, -
BardetBiedl , Alstrm , Jeune , Ellis van Creveldov , Sensenbrenner ) . , (4).

, , (ADPKD s PKD1 PKD2
1 2), (ARPKD s PKHD1
), (s NPHP1NPHP11, NPHP1L, SDCCAG8 ) (
).
(5, 6).
,
,
, ,
(CNF) (FSGS) (7, 8). CNF (NPHS1)
,
FSGS (NPHS2)
.

, (9).
,
, .
CNF FSGS.
CNF-, , ,
- , Ki-67 -3 . .

FSGS-.

(10).
186
10.

,
CNF FSGS
. . CNF-,

, . .
FSGS-, CNF-. CNF- i FSGS-
.
. ,
, .
CNF- FSGS- ,
.
.
,
.
CNF- FSGS- ,
. , ()
, .

,
. ,
187
, -
,
.
CNF FSGS , () .
CNF-
FSGS- ,

.

,
.

. ,
.
1.
CNF- FSGS.

.

Ki-67

();
188
10.
1. Gascue C, Katsanis N, Badano JL.Cystic diseases of the kidney: ciliary dysfunction

and cystogenic mechanisms. Pediatr Nephrol 2011; 26:1181-95.
2. Farnum CE, Wilsman NJ. Axonemal positioning and orientation in threedimensional space for primary cilia: what is known, what is assumed, and what
needs clarification.
3. Dev Dynamics 2011; 240:2405-31.
4. Saraga-Babi M, Vukojevi K, Boina I, i sur. Ciliogenesis in normal human
kidney development and post-natal life. Pediatr Nephrol 2012; 27:55-63.
5. Waters AM, Beales PL. Ciliopathies: an expandinf disease spectrum. Pediatr
Nephrol 2011; 26:1039-56.
6. Putoux A, Attie-Bitach T, Martinovic J, et al. Phenotypic variability of BardetBiedl syndrome: focusing on the kidney. Pediatr Nephrol 2012; 27:7-15.
7. Calinsecu-Tuleasca A-M, Bottani A, Rougemont A-L, et al. Caroli disease,
bilateral diffuse cysric renal dysplasia, situs inversus, postaxial poydactyly, and
preauricular fistulas: a ciliopathy caused by a homozygous NPHP3 mutation.
Pediatr Nephrol 2013; 172: 877-81.
8. DAgatiVD. Pathobiology of focal segmental glomeruloscelrosis: new
developments. Curr Opin Nephrol Hypertens 2012; 21:243-50.
9. Done SC, Takemoto M, He L, et al. Nephrin is involved in podocyte maturation
but not survival during glomerular development. Kidney Int 2008; 73:697-704.
10. Haltia A, Solin ML, Holmberg C, et al. Morphological changes suggesting
abnormal renal differentiation in congenital nephrotic syndrome. Pediatr Res
1998; 43:410-4.
11. Saraga M, Vukojevi K, Krelj V, i sur. Mechanisms of cystogenesis in nephrotic
kidneys: a histopathological study. BMC Nephrology 2014; 15:1471-2369.
189
11.
:
.
:
.
11.
11.1. ,

,

,
,
()
, . 25% ,
( 10% 43%).

.
.
. .
. ,
, , ,
, , .
6
6 (1).

, breath holding spells,
. , . (
4,6-4,7%) 6. 18. . ,
() . , , 15
, , , . . ,
,
. , ,
193
. , 7. 8. .
.
.
. . ,
. 23% 38%
- (2)
, , . long Q-
. , .
.
(, ).

, .

. ,
(0,01 / 2-3 ) 40 / .

.

.
, , , .
30 40 Hg .
15% 25% .
13 , 33 51% 5
.
. .
, , , (3).
194
11.
. , 50%.
, , ,
, .
, , , , , , , , , , . 1-2
, , , .

, .
, .
,
.
.

: , ,
, , , , .
,
.

.
5 .
, .
.
- , - , . , 10%
5 .

()
, ,
. ,

.
.
195

, .
1,4:100.000 3,4:100.000 15 24 . 1-9%.
11-46% e .
67% ,
5 (4). . (2012)
, , . (25%)
(, , -43%) (5).
(2007)
,
. (269:
83 ) (6). 47% . , .
.

?
,
, ( ), ,
,
.
.
( )
31-46% , (42%), (26%) (19%).

(, , , , , ).
, .

( ), . , . ,
.
.
.
.
. , , ,
196
11.
, ,
. .
.
18% 72% (4).
1. Kim SH, Kim H, Lim BC, et al. Paroxysmal nonepileptic events in pediatric
patients confirmed by long-term video EEG monitoring - single tertiary center
review of 143 patients. Epilepsy Behav 2012; 24:336-40.
2. Rody SM. Breath holding spells and reflex anoxic seizures. In: Swaiman KF,
Ashwal S, Ferriero DM, Schor NF (editors). Swaiman,s Pediatric Neurology:
Principles and Practise, 5th ed, Elsevier Saunder, China, 2012; 900-904.
3. Friedman NR, Ghosh D, Moodley M. Syncope and paroxyasmal disorders other
than epilepsy. In: Swaiman KF, Ashwal S, Ferriero DM, Schor NF(editors).
Swaiman,s Pediatric Neurology: Principles and Practise, 5th ed, Elsevier Saunder,
China, 2012; 905-925.
4. Reilly C, Menlove L, Fenton V, et al. Psychogenic nonepileptic seizures in children:
a review. Epilepsia 2013; 54:1715-2013.
5. Szabo L, Siegler Z, Zubek L, et al. A detailed semiologioc analysis of childhood
psychogenic nonepileptic seizures. Epilepsia 2012; 53:565-70.
6. Patel H, Scott E, Dunn, et al. Nonepileptic seizures in children. Epilepsia 2007;
48:2086-92.
197
11.2.
,
,
,
, .
(International Headache Society - IHS) - (1).

() , (2).
. 1%.
.
, , , .
CACNA 1 (3). .
. 2. 8. ,
. , .
.
( ), , , , .
, (). . .
1 (ICHD III, 2013) (1) .
1.
A. , .
. , / ,

.
1.
4.
2.
5.
3.
.
.
198
11.
: , / , .
. , , , , ,
. .
. .
. .
1/3 .

(4).
. 2-2,6%, .
. . ,
(CACNA1A).
. ,
. ,
. : , ,
, / .
. (5). ( 5 ), . 2 4 (5
-8 ), . ,
. (,
), . 2 (ICHD III, 2013) (1). 36-62%.
2.
. 5
. ,
,
.
1.
4.
2.
5.
3.
. ,
.
199
. .
. . .
.
. , (),
, , ,
, , , .
. (2-16 ).
(24-62%) (4,6).
. , .
.

()
, .
. 1-3%, 3/100.000
(7). 5 (: 4,6-5,3).
67-82% .
, (82%) .
.
. 4 :
1,5 , (,
, , , ).
. 41 , 6 /, . a . , , ,
, , , /.
, . ( 6 ) .
2 10 . , . (, , ),
(, , ,), (, , ).
. 3
(1). , 10% .
(8),
(1),
2-18 . , , , .
200
11.

,
.
3.
. 5 , .
.

. :
1. /
2. 1 10
3. 1
.
. je
. , , , , , - ,
.
.
. . (, ).
.
() .
.
-, , , , (8). .
. , . 10 . 18. 75% .
1. The international classification of headache disorders, 3rd ed. Cephalalgia 2013;

33:629-808.
2. Basheer SN. Paroxismal torticollis. J Pediatr Neurol 2010; 8:69-71.
3. 3. Rosman NP, Douglas LM, Sharif UM, et al. The neurology of benign paroxismal
torticollis of infancy: report of 10 new cases and review of the literature. J Child
Neurol 2009; 24:155-60.
201
4. Abu-Arafeh I, Russell G. Paroxysmal vertigo as a migraine equivalent in children:

a population-based study. Cephalalgia 1995; 15:22-5.
5. Cuvellier JC, Lepine A. Childhood periodic syndromes. Pediatr Neurol 2010;
42:1-11.
6. Krams B, Echenne B, Leydet J, et al. Benign paroxismal vertigo of childhood:
long-term outcome. Cephalalgia 2010; 31:439-43.
7. McOmber MA, Shulman RJ. Pediatric Functional Gastrointestinal Disorders.
Nutr Clin Pract 2008; 23:268-74.
8. Li BUK, Lefevre F, Chelimsky GG, et al. North America Sciety for Pediatric
Gastroenteroloy, Hepatology and Nutritin Consensus Statement of the
Diagnosis and Management of Cyclic Vomiting syndrome. J Pediatr Gastroentrol
Nutr 2008; 47:379-83.
202
11.
11.3.

,
,
(1).

(2).
( -)
( ). ,
,
, .

, .

,
..
. . , (2).

0.5-2 . , .
. , 15 .
(1,2).
2 .
10 % (3).

, ,
.
, (2).
203

, .
( ),
, (
). ,
(1,2).
0,55 , ,
15 . 1 2.
. (1,2).

, ( , , ),
/
. ,
(2,4).
, ,
( , ), .
(5).
, .
2 .
. (6).
1
2, .
. (7).

. , , , ,
, ( ).
15-45 ,
.
. .
(8).
204
11.

.
. ,
, 30 (9).
. (2).
, ,
,
(2).
( ) 5 .
, , ,
. (2).
4-12 .

. 5-15 . 5- (2,10).
()
. , ,
.
(. , ),
(. , ,
) . 5-15 (2).
.
.
3-5 . , ,
. (2).
.
.
, .
,
( ) (2).
18
. (
), , ,
. , , , , .
. (, ) (2).
205
1. Chiu S. Pediatric sleep disorders. Dostupno na : http://emedicine.medscape.com/

article/916611, preuzeto 2.4.2014.
2. American Academy of Sleep Medicine. International Classification of sleep
disorders : diagnostic and coding manual. 2nd ed. Westchester, IL, 2005.
3. Aloe F. Sleep bruxism treatment. Sleep science 2009; 2:49-54.
4. Lloyd E. What is nocturnal myoclonus? Dostupno na: http://www.wisegeek.com/
what-is-nocturnal-myoclonus.htm, preuzeto 24.3.2014.
5. Vetrugno R, Plazzi G, Provini F, et al. Excessive fragmentary hypnic myoclonus:
clinical and neurophysiological findings. Sleep Medicine 2002; 3:73-6.
6. Roze E, Bounolleau P, Ducreux D, et al. Propriospinal myoclonus revisited: clinical,
neurophysiologic and neuroradiologic findings. Neurology 2009; 72:1301-9.
7. Senevirante U. Facio-mandibular myoclonus: a rare cause of nocturnal tongue
bitting. Epileptic Disord 2011; 13:96-8.
8. Provini F, Plazzi G, Lugaresi E. From nocturnal paroxysmal dystonia to nocturnal
frontal lobe epilepsy. Clin Neurophysiol 2000; 111(Suppl 2):S2-S8.
9. Guilleminault C, Hagen C, Khaja A. Catathrenia: parasomnia od uncommon
feature of sleep disordered breathing? Sleep 2008; 31:132-9.
10. Bruni O, Ferri R, Miano S, et al. L-5-Hydroxytryptophan treatment of sleep
terrors in children. Eur J Pediatr 2004; 163:402-7.
206
11.
11.4.

,

,
,
, / . ,
. : ,
, , , , , , , , ,
, , , (1).
,
.

()
,
(, ) .
ATP1A3 (Na+/K+ ATP a)
Na K . ,
. , , , . , , ,
(). , .
207
5 10 , ,
, (2).

() , , , .
, .
, .
, ,
.
, .
2 4.
() ,
,
.
, .
. ,
.
. ,
. ,
2-4 (3).
, , . ( ) ( ).
, , , . , , , . , ,
, , , .
, .
, , , , , , .
,
. . Tourett-
208
11.

. , 20%
. .

. ,
, (4).
(shuddering/shivering)
. , ,
.
, , , , ,
. , . .
(5).

() ( 30 ) ,
.
12 , . -. , ,
. 10% 20%
, 50% . .
10-30 (1).

, ,
. .
, -.
(1).
209

. , , ( ),
.
(1).

: , . , ,
- .

. ,

. .
. (6).

()

.
.

: , . ,
, .
210
11.
.

, GLR1 (
5q33.1) i SLC6A5( 11p15.2). -. (1).
1. Fiedman N, Ghosh D, Moodley M. Syncope and paroxysmal disorders other theb

epilepsy. In: Swaiman K (ed): Swaimans Pediatric Neurology, Elsevier Sauders,
2012; 904-25.
2. Sweney M, Silver K, Gerard-Blanluet M, Pedespan J, et al. Alternating hemiplegia
of childhood: early characteristics and evolution of a neurodevelopmental
syndrome. Pediatrics 2009; 123:e534-41.
3. Rosman N, Douglass L,Sharif L, et al. The Neurology of benign paroxysmal
torticollis of infancy: report of 10 new cases and review of the literature. J Child
Neurol 2009; 24:155-60.
4. Piacentini , Chang S. Habit Reversal Training for Tic Disorders in Children and
Adolescents. Behav Modif 2005; 29: 803-22.
5. Holmes G, Russman B. Shuddering Attacks Evaluation Using
Electroencephalographic frequency modulation radiotelemetry and videotape
monitoring. Am J Dis Child 1986; 140:72-3.
6. Egger J, Grossmann G,Auchterlonie I. Benign sleep myoclonus in infancy
mistaken for epilepsy. BMJ 2003; 326: 9756.
211
12.
:
.
:
.
12.
12.1.

,
,
()
, ,
, (1).
, , . je 1.
1.

-IgD

NF-
NF-
CIAS1
uckle-Wells
CIAS1
NMID ( - CIAS1
)
( , ., )
CD-2 -a
Blau
NOD2

() , (, ).
(2).
. (MEFV)
16 /, .
215
SC- -1, -1 (IL-1). IL-1

(NF) ,
6 (IL-6) .
, .
. (95%)
.
. (, , )
25% 75% . , ,
.
30% , ,
. ,
, (3).
.
,
(CRP), .
. , (694V, V726)
. , 694V ,
.

. FV .
FV ,
, .
,
.
, .
.
,
40 . .
.
216
12.
-
- () -
-,
(2). ,
() 10-15%,
,
.
, -1 IL-1.
, (
337 , V337I) .
,
. , 4 6 . , , .
,
,
. , . , , .
4 6 .

IgA IgD. . IgD 100
../. , , IgD
. 80% IgA.
, CRP, .
, , , , IL-1 ,
. .
, .
217

TNF- (. TNFreceptor associated periodic syndrome, RAPS)
- .
NF-1 (TNFRSF1A) (2). NF-1
NF, , , , ,
. NF-1 NF
NF. NF-1
, NF .
1 2 ,
. 7 RAPS.
80% . ,
.
60% ,
. 50% . ,
,
. , 7 ,
. , , 25%
RAPS (3).
, , CRP, , . IgD , 100 ..
TNF-1
(< 1 /).
(>20 )
. NF (),
NF-1 . , NF ,
(4).
218
12.

(familial cold urticaria, FCU familial cold autoinflammatory syndrome, FCAS) .
24 , , , .
uckle-Wellsov (WS) FCU
, ,
48 . .
FCU, WS .
(neonatal-onset multisystem inflammatory disease, NOMID)
. , ,
, , , . , NOMID
, . , ,
.
T ,
- CIAS1 a
(cold induced autoinflammatory syndrome 1) ,
.
(NF-kB) IL-1. CIAS1
,
, NOMID.
20 CIAS1 ,
(FCU) (WS, NOMID). IL-1
IL-1 (5).
PAPA ( , ,
)
CD-2- . . CD-2-
.
IL-1 .
219
Majeed
, . LPIN2 18
. .
IL-1 () , . , .
IL-1 .
Blau
-
, . NACHT NOD2/CARD15
. . , 50% , ,
. ,
, 90% . TNF .

,
, ,
(PFAPA) , , .
PFAPA , (6). . ,
, IL-1 IL-18
.
. 3 5 , 2 4 2 8 .
, , (50% ) (70% )
. .
.
, ,
PFAPA
220
12.
. 3 5 ,
.
, 1 / , PFAPA (
), . ( ),
,
.
PFAPA
, .
, ,
.
1. Hashkes PJ, Toker O. Autoinflammatory sydromes. Pediatr Clin North Am 2012;

59: 447-70.
2. Ozen S, Frenkel J, Ruperto N, Gattorno M. The Eurofever project: towards better
care for autoinflammatory syndromes. Eur J Pediatr 2011; 170:445-52
3. Lane T, Loeffler JM, Rowzencio DM, Gilbertson JA, Bybee A, Russell TL. AA
amyloidosis complicating periodic fever syndromes. Arthr Rheum 2013; 65:
1116-21.
4. Cantarini L, Rigante D, Lucherini DM, Cimaz R, Laghi Pasini F, Baldari CT. Role
of etanercept in the treatment of tumor necrosis factor-associated periodic fever
syndrome: personal experience and review of the literature. Int J immunopathol
Pharmacol 2010; 23:701-7.
5. Caorsi R, Federici S, Gattorno M. Biologic drugs in autoinflammatory syndromes.
Autoimmun Rev 2012; 12:81-6.
6. Vigo G, Zulian F. Periodic fevers with aphthous stomatitis, pharyngitis and
adenitis PFAPA. Autoimmun Rev 2012; 12:52-5.
221
12.2. HENOCH
SCHONLEIN
,
,
,
Henoch Schonlein
su

,
.
Henoch-Schnlein
, .
. Henoch-Schonlein ()
()
, , (1).
Henoch-Schnlein .
13-15/100 000.
2-11 . 5,5 . 75% 10 .
, 50% .
(2).

.
(, , ). , , , Ebstein-Barr , , (3).
222
12.

, , ,
, .
, .

(4). , , . (5).
, ,
.
. (6). . (7).
-.
Peru . 254 ,
: (100%), (66%), (56%) (30%) (8). e
e
e 57-69% (8). . ,
(8).
.
2-3 . , .

4 e.
1,6-3% (9). 20%
20 (9).
, .
,
0,7-13,6% (10).
( ), (10).
223
1. Shin JI, Kim JH, Lee JS. The diagnostic value of IgA deposition in HenochSchnlein purpura. Pediatr Dermatol 2008; 25:1401.
2. Saulsbury FT. Clinical update: Henoch-Schonlein purpura. Lancet 2007; 369:9768.
3. Yang YH, Chuang YH, Wang LC, et al. The immunobiology of Henoch-Schonlein
purpura. Autoimmun Rev 2008; 7:17984.
4. Tarvin SE, Ballinger S. Henoch-Schnlein purpura. Curr Paediatr 2006; 16:259-63.
5. Gedalia A. Henoch-Schonlein purpura. Curr Rheumatol Rep 2004; 6:195202.
6. Chang WL, Yang YH, Lin YT, et al. Gastrointestinal manifestations in HenochSchonlein purpura: a review of 261 patients. Acta Paediatr 2004; 93:142731.
7. Kelly A, Tizard EJ. Vasculitis in Children. Paediatric and Child Health 2010;
20:65-72.
8. Peru H, Soylemezoglu O, Bakkaloglu SA, et al. Henoch Schonlein purpura in
childhood: clinical analysis of 254 cases over a 3-years period. Clin Rheumatol
2008; 27:1087-92.
9. Eleftheriou D, Brogan PA. Vasculitis in Children. Best Pract Res Clin Rheumatol
2009; 23:309-23.
10. Ebert EC. Gastrointestinal Manifestations of Henoch-Schonlein Purpura. Dig
Dis Sci 2008; 53:2011-9.
224
12.
12.3. ,

,

,
-
.
(1).
.
, , .
: ( 70%, 30%, 25%),
, , (),
, (2).
: 1. (CD14 TLR2 i TLR4), 2. ,
3. DNA ( CpG) DN (, , ,
, )
, 4. HSP90, 5. Th (Th1-Th2). ,
. (3)

: heat shock (HSP), , ,
, , IFN. HSP
, ,
.
, ,
, , , ,
(4).
225

,
, .

, (5).
, , ,
.
, , .
PRP (Proline rich peptides),
, . Crohn
.
, (tight junction, zonula
occludens), .
. , .
, ,
.
-
,
.

, , ,
.
, ,

(6).
,
, ,
.
, ( , , ) .
226
12.

- -,
.
, ,
- , , - .
: (1)
(Clostridium difficile x- A i B Clostridium botulinum x, Clostridium
botulinum C3 toxin, Escherichia coli cytotoxic necrotizing factor-i 1 i 2 (CNF); (2)
(Bacteroides fragilis toxin (BFT), , Serine protease autotransporter- enterobacteraceae-a, Vibrio
cholerae hemagglutinin protease-a), (3) , (zonula occludens , Clostridium
perfringens (CPE), Vibrio cholerae RTX (repeats-in-toxin) .
.
Deoxynivalenol (DON), , .
in vitro ,
,
,
4, . ,
.
,
, , ,
, , , (7).

: -, , , , ,
, , , , ,
, , ,
, , , ,
, , , , , , , , .
227

. , ,
.
.
1. Lieb JD, Beck S, Bulyk ML, et al. Applying whole-genome studies of epigenetic
regulation to study human disease. Cytogenet Genome Res 2006; 114:1-15.
2. Shiota K. DNA methylation profiles of CpG islands for cellular differentiation
and development in mammals. Cytogenet Genome Res 2004; 105:325-34.
3. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence
of the human genome. Science 2001; 291:1304-51.
4. Hake SB, Xiao A, Allis CD. Linking the epigenetic language of covalent histone
modifications to cancer. Br J Cancer 2004; 90:761-9.
5. Ansel KM, Djuretic I, Tanasa B, et al. Regulation of Th2 differentiation and Il4
locus accessibility. Annu Rev Immunol 2006; 24:607-56.
6. Lee GR, Kim ST, Spilianakis CG, et al. T helper cell differentiation: regulation by
cis elements and epigenetics. Immunity 2006; 24:369-79.
7. Cui K, Tailor P, Liu H, et al. The chromatinremodeling BAF complex mediates
cellular antiviral activities by promoter priming. Mol Cell Biol 2004; 24:4476-86.
228
13.
:
.
:
.
13.
13.1.

, - ,
,
, , /, / .
, , .

( 1)
( 2).
(1).
. ,
() () . , , , , .
(, ) .

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

, , , Beckwith-Wiedemann
, Denys-Drash WAGR ( , ,
, ).
231
, , (2).
,

(3).
1.

, ,
, , ,
(),
, ,
232
13.
2.
//
55%
35%
10%
10% ,
55%
20%
5%
30%
15%
,
4%
,
,
10%
,
23%
21% 2%
15%
, ,
12%
5%
, ,

,
6%
,
1. Hong T. Approach to abdominal mass. Dostupno na: http://learnpediatrics.com/

body-systems/gastrointestinal/approach-to-abdominal-mass/ Preuzeto 2011.
2. Pizzo PA, Poplack DG, editors. Principles and Practice of Pediatric Oncology, 6th
ed. Lippincott Williams and Wilkins, Philadelphia; 2010.
3. Rahhal RM, Eddine AC, Bishop WP. A child with an abdominal mass. Pediatric
Rounds. Hosp Physician 2006; 37-42.
233
13.2.

,
,
()
. ,
, 150 (Virchow) .

(1,2).
1,3 100.000 , 15 .
22 . , 2-3%
.
(35%) (30-35%) (1,2).
, e , .
95% (3).
2/3 . : , , ,
, . j , . , ,
, .
. ,
, INDC (International Neuroblastoma
Diagnostic Criteria)
, , . ,
(3, 4).
,
,
234
13.

---.
, .
,
, (-, - )
(1, 2, 4).
25 .
double minut ,
1, . , : ,

, N-myc (5).
Shimada (1984. )
.
, : .
(International Neuroblastoma Pathology Classification System) Shimadine (1, 2).
(International Neuroblastoma
Staging System INSS) , 1986. .
, ,

(6, 7).
: , .
N-myc , 20% , .
17q, 1p36
11q14-22 (1, 2, 7).
90%

. , IV ,
25-30%.
, ,
(7, 8).
235
1. Papaioannou G, Kieran McH. Neuroblastoma in childhood: review and

radiological findings. Cancer Imaging 2005; 5:116-27.
2. Weinstein LJ, Katzenstein MH, Cohn LS. Advances in the diagnosis and treatament
of neuroblastoma. Oncologist 2003; 8:278-92.
3. Metha K, Haller OJ, Legasto CA. Imaging neuroblastoma in children. Crit Rev
Comput Tomogr 2003; 44:47-61.
4. Liu W, Zheng J, Li Q. Application of imaging modalities for evaluating
neuroblastoma. J Pediatr Endocrinol Metab 2013; 26:1015-20.
5. Sridhar S, Al-Moallem B, Kamal H, Terrile M, Stallings RL. New insights into the
genetics of neuroblastoma. Mol Diagn Ther 2013; 17:63-9.
6. Monclair T. The new international neuroblastoma risk group staging system
implications for surgeons. In: International Society of Paediatric Oncology
Education Book 2006. http://www.siop.nl. Preuzeto 05.02.2007.
7. Bernardi B, Cohn LS. Riskbased treatment for children with neuroblastoma. In
International Society of Paediatric Oncology Education Book 2005. http://www.
siop.nl. Preuzeto 05.02.2007.
8. Yalin B, Kremer LC, Caron HN, van Dalen EC. High-dose chemotherapy
and autologous haematopoietic stem cell rescue for children with high-risk
neuroblastoma. Cochrane Database Syst Rev 2013; 8:CD006301.
236
13.
13.3.
e
,
,

,
. (Wilms) , . I II
90% (1).
. ,
, () .
1899. . - 11 (2).
.
, , 5%
(. ), , (. ).
5. . 11. .
(,
, ) (3).

. , , , , , .
, , . , , .
. (
)
.
(4).
,
: I - , , , ;
237
II - ,
, , ,
; III - ,
, ,
, ,
; IV - (, , , ) ; V - a (4).
(/), ,
.
,
.
,
( ).
,
(5).
,
,
, , (Socit international oncologie
pediatrique - SIOP). ( )
/ .
. , () (5).

. ,

.
,
.
.
85% -
90%, IV 70%.
8 , 2006. 2013. , 24
. 23
, 47,8% , 52,2% .
3,4 (. 1 ; . 9 ).
(39,1 %) (34,8 %),
238
13.
(17,4 %) , (8,7 %).

,
60,9 % . 47,8%
, 39,1% ,
13% . ,
26,1% , 8,7% ,
13% .
, (78,3%) .
(26,1%), 50%
, 33% , 17%
. ,
- (NSE) (LDH) , NSE, 78,9% LDH.
5 .
, 30,4%
.
je o ,
.
22/23 . .
,
.
1. Gatta G, Botta L, Rossi S, et al; EUROCARE Working Group. Childhood cancer

survival in Europe 1999-2007: results of EUROCARE-5--a population-based
study. Lancet Oncol 2014; 15: 35-47.
2. Rather MI, Swamy S, Gopinath KS, et al. Transcriptional repression of tumor
suppressor CDC73, encoding an RNA polymerase II interactor, by Wilms tumor
1 protein (WT1) promotes cell proliferation: implication for cancer therapeutics.
J Biol Chem 2014; 289:968-76.
3. Sharpe CR, Franco EL. Etiology of Wilms tumor. Epidemiol Rev 1995; 17:415-32.
4. Friedman AD. Wilms tumor. Pediatr Rev 2013; 34:328-30.
5. Powis M, Messahel B, Hobson R, et al. Surgical complications after immediate
nephrectomy versus preoperative chemotherapy in non-metastatic Wilms
tumour: findings from the 1991-2001 United Kingdom Childrens Cancer Study
Group UKW3 Trial. J Pediatr Surg 2013; 48:2181-6.
239
13.4.

,
.
.
5% .
5 . je 1:1,4 .
:
. ,
(35-40%),
(22%), (18%).
, .

.
. :
. 60%. , .

, .
,
.
. 15%. , .
, .
240
13.

, (, , -),
(1).

. : Li-Fraumeni, BeckwithWiedemann, Costello, Noonan e. - TP53,
2 13 1 13, 11p15, - IGF2. .
,
.
. , ,
.

. T . 1 .
Ta 1.
,
, ,
, , , , , .
, ,

, ,
, , , .
,

McDowell HP: Update on childhood rhabdomyosarcoma. Arch Dis Child 2003; 88:354357.
241
, , .
, , , , , . (2).

.
. ,
. .
.
.
(I-III ).
-- I
-- II - .
-- III
-- IV -
, , (TNM)
-- (T1) (T2)
-- (N0), (N1), (NX)
-- - (M0), (M1)

-- 1 , , ( ) ( )
-- 2 N0 NX
-- 3 - , N1 5 cm N0
NX 5 cm
-- 4 .

-- 1-3 I-II ( III )
-- 1 III

-- 2-3 III ( )
-- 4 IV 1 - 14 (3)
242
13.
,
.
. .
, . ,
.
,
. 8090%.
70%.
j .
, , .
(4).
1. Arndt C. Soft Tissue Sarcomas In: Kliegman RM, Stanton BF, St. Geme JW,
Schor NF, Behrman RE, editors. Nelson Textbook of Pediatrics, 19th ed. ElsevierSaunders, Philadelphia, 2011;1710-4.
2. McDowell HP. Update on childhood rhabdomyosarcoma. Arch Dis Child 2003;
88:354357.
3. Boggs W. Presenting Characteristics Should Drive Rhabdomyosarcoma
Staging in Kids. Medscape. Sep 2 2013. Available at http://www.medscape.com/
viewarticle/810327. Accessed Mar10 2014.
4. Punyko JA, Mertens AC, Baker KS, et al. Long-term survival probabilities for
childhood rhabdomyosarcoma. A population-based evaluation. Cancer 2005;
103:1475-83.
243
13.5.

,
,
.

7% a 20
. .
.
, 8
12 , 11 14 . , .
, . , , ,
, , , , (1).
,
.
:
1.
--
--
2.
--
--
-- ( + )
244
13.
3.
4.
5.

.
.
. 1 (2).
1.
50-60%
5-15%
10-30%
,
, ,

35%
60%
40%
4%
50-60%
5%
,
,
50-60%
20-30%
10-20%
10%
( , -
,
)
60-65%
5-10%
15-30%
25%
, - 15-20%
80-85%
15%
245

,
. ,
.
,
.
:
- (AFP), ko
(. yolk sac),
- (beta-HCG),
, ,
(LDH),
.
(Childrens Cancer Group)
(Pediatric Oncology Group),
2.
2.
II
III
IV

,
, , ,
, , .
, , , .
,
.
246
13.
, a
15% 20%. y , 80% (3).
1. Gobel U, Schneider DT, Calaminus G, et al: Germ-cell tumors in childhood and

adolescence. GPOH MAKEI and the MAHO study groups. Ann Oncol 2000;
11:263-71.
2. Rescorla FJ. Pediatric germ cell tumors. Semin Surg Oncol 1999; 16:144-58.
3. Herzog C. Gonadal and Germ Cell Neoplasms. In: Kliegman RM, Stanton BF, St.
Geme JW, Schor NF, Behrman RE (eds). Nelson Textbook of Pediatrics. 19th ed.
Elsevier-Saunders, Philadelphia, 2011; 1723-4.
247
14.
:
.
:
.
14.
14.1.
1

,
,
1 (1)
: ,
e () ,
, , ,

( , ).
: 1. , 2. , , 3.
4. .
.
, ,

1.

1 (1). 50%
1 12 .
( )
(1).
, () (2).
251
Ea ,
, (3).
(4),
, ,
, . , , . .
,
. , -
,
(4). , , (4).
,
,
(4).

- ( ),
, (), ( ). ,
(4).

, ,
(4).
252
14.
j

, , , .
DCCT , ,
, (1). , . (19951998. .)

(HbA1c <7,6% 17,5%),
(HbA1c 1995. . - 8,7%, 1998. . - 8,9%)
(2).
.
, , (5).
(6).
HbA1c
, .

1 . , , HbA1c.
()
.
, . HbA1c ,
. 24
, , ,
6 23 (7, 8).
.
253

HbA1c.
(9).
( ) (10).
.
HbA1c
(9). DCCT
HbA1c , . , HbA1c
.
1
. HbA1c 7,0% (
7 ) 10,7 / ,
9,0 / (9).

HbA1c. HbA1c . (International Society for Paediatric Diabetes)
HbA1c 7,5% (58 mmol/mol) .

1

,
, 1 :
, , , . 2013.
2009. .
2013
(92%)
4-5 2009. (70%),
254
14.
(80% 44%), (3%

4%). -
HbA1c 2009. 8,5 1,6%, 2013. 7,8 1,0 . ( /100 /) 2013. (9%)
2009. (7,6%).
:
4-5 , ( -
), e -
, .

a 1.
1. The Diabetes Control and Complications Trial Research Group. Effect of

intensive diabetes treatment on the development and progression of long-term
complications in adolescents with insulin-dependent diabetes mellitus: Diabetes
Control and Complications Trial. Diabetes Control and Complications Trial
Research Group. J Pediatr 1994; 125:177-88.
2. Holl RW, Swift PG, Mortensen HB, et al. Insulin injection regimens and metabolic
control in an international survey of adolescents with type 1 diabetes over 3 years:
results from the Hvidore study group. Eur J Pediatr 2003; 162:22-9.
3. Swift PG. Diabetes education in children and adolescents. Pediatr Diabetes 2009;
10(Suppl 12):51-7.
4. Pihoker C, Forsander G, Wolfsdorf J, et al. The delivery of ambulatory diabetes
care to children and adolescents with diabetes. Pediatr Diabetes 2009; 10(Suppl
12):58-70.
5. Garcia-Garcia E, Galera R, Aguilera P, et al. Longterm use of continuous
subcutaneous insulin infusion compared with multiple daily injections of glargine
in pediatric patients. J Pediatr Endocrinol Metab 2007; 20:37-40.
6. Tamborlane WV, Beck RW, Bode BW, et al. Continuous glucose monitoring and
intensive treatment of type 1 diabetes. N Engl J Med 2008; 359:1464-76.
7. Danne T, Datz N, Endahl L, et al. Insulin detemir is characterized by a more
reproducible pharmacokinetic profile than insulin glargine in children and
adolescents with type 1 diabetes: results from a randomized, double-blind,
controlled trial. Ped Diabetes 2008; 9:554-60.
255
8. Plank J, Bodenlenz M, Sinner F, et al. A double-blind, randomized, dose-response

study investigating the pharmacodynamic and pharmacokinetic properties of the
long-acting insulin analog detemir. Diabetes Care 2005; 28:1107-12.
9. Rewers M, Pihoker C, Donaghue K, et al. Assessment and monitoring of glycemic
control in children and adolescents with diabetes. Pediatr Diabetes 2009; 10(Suppl
12):71-81.
10. Donaghue KC, Chiarelli F, Trotta D, et al. Microvascular and macrovascular
complications associated with diabetes in children and adolescents. Pediatr
Diabetes 2009; 10 (Suppl 12):195-203.
256
14.
14.2.

,
,

, .
(4) (3),

.

95%
- ().
,
. 60% . . 5. ,
(0,1-3,0/100000) .
5-6 (1,3,4).
, ( 2% ).
, . , ,
, , (1,4).
257

, , , .
(8+)
(4+) -
(T). .
, -
.
(1,3).

. , ,
.
.
, , 4 3 . , ,
. 90%
. .

99%; , - 80%; , , - 60%; , ,
, () - 45%; ,
- 30%; , , - 15%. 5-8 .
, .
- ( 85%). . ( ):
258
14.
(50 - 75 %). , , . ,
( ), (
) (1,3,4).

: () () . .

. , ,
4 3, . ,
, .
, . ( )
.
0,2-1,0 //
. 1 3 ,
1-3 . .
, ,
. . .
. ,
.
.
, , , ,
. - .

, , , (6-30%).
( 500/ccm), (0,3%), ,
, .
, . . ,
,
259
.
,
. 2009. ,
.
. (FT4)
4 -8 , , 8-12
, .
30-50%, .
2
( 30%), ( 75% 6
). ,
, ( ,
10 ) ( )(1,2,3,4).

, 5 . , 3-6
. .
25% ,
25%. .
(BMI),
( F3) F4, .
, , .
.
TSH . , , , (2-15%), .
. (2,3,4,5).
260
14.
(131)
.
.
, .
. 131 ,
, .
,
. (36 ) 116 3-19
: . .
.
, .
. 5 ,
(4,5).
.
( 4-8, 8-12 ). , , .
. ,
.
1. La Franchi S. Hyperthyroidism. In: Nelson Textbook of Pediatrics, Elsevier

Saunders, Philadelphia, 2004; 1884-6.
2. Cappelli C, et al. Prognostic value of thyrotropin receptor antibodies in Graves
Diesese: A 120 months prospective study. Endocr J 2007; 54:713-20.
3. Kaguelidou F, Carel JC, Leger J. Graves disease in childhood: advances in
management with antithyroid drug therapy. Horm Res 2009; 71:310-7.
4. Leger J, Carel JC. Hyperthyroidism in childhood: Causes,when and how to treat.
J Clin Res Pediatr Endocrinol 2013; 5(Suppl 1):50-6.
5. Rivkees SA. Pediatric Graves disease: Controversies in management. Horm Res
Paediatr 2010; 74:305-311.
261
14.3. -
?
,

,
60-80%
! 2% 8%,
.
1,5 . , . ,
/-
-.
- (1).
1, , , . ().
() 1, ,
, - .
, (, , ).
.
: , - - (2). (), .
90%
(3). (
262
14.
- 3%), . - .
: ,
(, )
, , .
5-
(
)
. ,
.

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

() (4). .
() () ,
.
2 5- . - 66%
100%. ,
- .
,
5- .
20% .
263

- , Ferriman-Gallwey-.
9 (, , ,
, , ) 0
4, , 8 .
.
. , (5).
.
.

80/ ( 2.8/) 0.8/ 3.5/
( 5 ).
FSH:LH (1:3) . 17-OHP 3-4 / ( 10/).
, . ( ) .
(),
(), GnRH .
() (6) :
LH DHEA,
,
(SHBG) .
.
Yasmin, Jeanin, Diane 35, Cilest, Novynette, Cycloprogynova, Qlaira, Cyclocur.
264
14.
,
, ,
(Androcur) (Aldactone),
(Flutasin).
GnRH () (LH) .
-.
,
GnRH .
,
GnRH .

, .
FDA
, , , (7).
1. Rosenfield RL. Hirsutism. N Engl J Med 2005; 353:2578-88.

2. Roland-Martin MB, Witchel SF. Hypernadrogenism in children and adolescent.
In: Pescovitz OH, Eugster EA (editors): Pediatric Endocrinology, 1st ed.,
Lippincott Williams&Wilkins, Philadelphia 2004; 360-75.
3. Witchel SF. Hirsutism and Polycystic Ovary Syndrome. In: Lifshitz F (editor):
Pediatric Endocrinology, 5th ed. Informa Healthcare Inc, New York, 2007; 325-43.
4. Pirard-Franchimont C, Pirard GE. Alterations in hair follicle dynamics in
women. Bio Med Res Int2013; ID 957432.
5. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
Revised 2003 consensus on diagnostic criteria and long-term health risks related
to polycystic ovary syndrome. Fertil Steril 2004; 81:19.
6. Sedlecki K. Kontracepcija i reproduktivno zdravlje. Vodi za kombinovanu
hormonsku i intrauterinu kontracepciju, Beograd, 2006.
7. Stankiewicz M, Norman R. Diagnosis and management of polycystic ovary
syndrome: a practical guide. Drugs 2006; 66:903-12.
265
14.4.
,
,
,

.
2-2,5 . , 97% 13, 14 .
, ( ) . , .
,
-- . .
(CDGP, Constitutional Delay of Growth
and Puberty) .
, , , , , . , ,
. ,
.
CDGP , . , , 50-80%
, . -, .
: ,
266
14.
(LH) (FSH) (5-10% 25% ), LH FSH

(10% 20% ) -- ,
(20% ) (1,2).
, (,
, , , .) . / , .
,
.
, 4, . CDGP ,
. , , , . ( Bayley Pinneau).
, .

, , , ,
( ). IGF1
.
(1,2,3,4).

, . 18. . .
GnRH (Gonadotropin Realising Hormone) CDGP .
, (5).
267
, , .
( ).
50 .. 3-6 , 25-50.
100 (CDGP). ,
, ,
, . , (6).
200-250 2 (2-4 )
. , . ,
GnRH. . 1500
(LH-Pregnyl) (FSH-Menopur) 75 IJ ..
.
. (Ethinyl Estradiol) 2 , 6-12 5 ,
20 . 17 - ( ).
0,1625 24 , 6
0,625 . Medroxiprogestrone acetate (Progestogeni,
Progestini) 12
, . 5-10 7
( ) (7).

, .
, ,
, .
.
268
14.
1. Palmert M. Delayed Puberty: Diagnosis, Evaluation, and Management. Endocrine

Case Management. The Endocrine Society, Washington, 2013;339-47.
2. Vlaki J. Terapija hipogonadizma. Jugoslovenski pedijatrijski dani, Ni. Zbornik
radova, 2001:27-8.
3. Gajdos ZK, et al. Genetic determinants of pubertal timing in the general
population. Mol Cell Endocrinol 2010; 324:21-9.
4. Sedlmeyer IL, Hirsschhorn and Palmert MR. Pedigree Analysis of Constitutional
Delay of Growth and Maturtion: Determination of Familial Aggregation and
Inheritance Patterns. J Clin Enocrinol Metab 2002; 87:5581-6.
5. Coutant R, et al. Baseline inhibition B and antiMullerian hormone measurements
for diagnosis of hipogonadotropic hypogonadism (HH) in boys with delayed
puberty. J Clinical Endocrinol Metab 2010; 95:5225-32.
6. Hero ME, Norjavaar E, Dunkel L. Inhibition of estrogen biosynthesis with a potent
aromatase inhibitor increases predicted adult height in boys with idiopathic short
stature: a randomized controlled trial. J Clin Endocrinol Metab 2005; 90:6396-402.
7. Hindmarsh PC. How do you initiate estrogen therapy in a girl who has not
undergone puberty? Clin Endocrinol 2009; 71:7-10.
269
15.

:
.
:
.
15.
15.1.

,
,
: , ,
. , ,
, ,
() (1).
.
.
.
,
(
)
() ( - , ),
( ) .
,
() .
(Ventilator associated pneumonia ),
, ,
. ( ),
(Clostridium difficile, Candida).
, ,
, . :
273
, ( ) ,
( ) (
),
, ,
(2).
() .
.
1. (
,
();
2. ( , ).
.
1.
(
, );
2. (2).
, ,
,
.
, , .

. ( ) (2).
:
.
.
. .
.
274
15.
:
( )
, . , , , ;
- (3).
:

,
,
.

. () . ,

: (1,2).
:
(, )
.
(
).
, ,
. , (4)
: .
: .
. ,
(1,2).

: (.
) (). ,
(5)
:
,
275
Clostridium difficile.
(
)
ex juvantibus
( ,
) (5).
:
.
( ) (1,2).
:
,
.
(
). (5,6).
: , ,
.

(5).
:
. . 7-8
( ).
48-72h .
:

(5,6).
,
( ). ,
, ,

.
, ,
()
.
276
15.
1. Kollef MH, Fraser VJ. Antibiotic resistance in the intensive care unit. Ann Intern
Med 2001; 134:298.
2. Kollef MH. Bench-to-bedside review: Antimicrobial utilization strategies aimed
at preventing the emergence of bacterial resistance in the intensive care unit.
Published online: 27 June 2005. Crit Care 2005; 9:459-64.
3. Gerding DN. Antimicrobial cycling: lessons learned from the Aminoglycoside
experience. Infect Control Hosp Epidemiol 2000; 21:S12-S17.
4. Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheterrelated bloodstream infections in the ICU. N Engl J Med 2006; 355:2725.
5. Kollef MH, Vlasnik J, Sharpless L, Pasque C, Murphy D, Fraser V. Scheduled
rotation of antibiotic classes. A strategy to decrease the incidence of ventilatorassociated pneumonia due to antibiotic-resistant Gram-negative bacteria. Am J
Respir Crit Care Med 1997; 156:10408.
6. Hughes MG, Evans HL, Chong TW, et al. Effect of an intensive care unit rotating
empiric antibiotic schedule on the development of hospital-acquired infections
on the non-intensive care unitward. Crit Care Med 2004; 32:53-60.
277
15.2. -

,
,
-
,
.
, -
, .
, . ,
,
,
- (1).
- 20-60%
.
90%.
- Escherichia coli, Klebsiella spp,
Enterobacter spp, Pseudomonas aeruiniosa, Serratia spp, Proteus spp, Acinetobacter
baumanii (1, 2).

-
, (, , ), (, , ,
), , , , , (
, ) (, ,
). ,
(1).
278
15.
-
- . - ()
. , , , - .
, , ,
, .

.
, -1 (1).

( 8%
). 50%. in vitro
. (- ) 48h
72h 50% -
2 ,
.
( !).
, , ,
(3, 4).
-
( , ,
, ).
, .
,
. . ,
Pseudomonas aeruginosum, ,

279
, , .
.
. ( )
Pseudomonas aeruginosum,
Acinetobacter baumannii i Stenotrophomonasom. ( , ,
).
Enterobacteriaceae, Acinetobacter i Stenotrophomonas spp.
Pseudomonas Proteus (5).
- .
:
, . ,
, . . ,

, .
-
,
.
Pseudomonas aeruinosom
( 50%) .
- ( Pseudomonas aeruinosa Acinetobacter baumannii). In vitro
Pseudomonas aeruginosa - . in vitro
- (6, 7).
.

, , ,
280
15.
.
(1).

.
In vitro
( ). !
Pseudomonas aeruginosom - ( -), .
1. Bone RC. Gram-negative sepsis: a dilemma of modern medicine. Clin Microbiol

Rev 1993; 5:57-68.
2. Pop-Vicas, Opal SM. The clinical impact of multidrug-resistant Gram-negative
bacilli in the management of septic shock. Virulence 2014; 5:189-95.
3. Couto RC, Carvalho EA, Pedrosa TM, et al. A 10-year prospective surveillance of
nosocomial infections in neonatal intensive care units. Am J Infect Control 2007;
35:183-9.
4. Micek ST, Welch EC, Kan J, et al. Empiric combination antibiotic therapy is
associated with improved outcome against sepsis due to Gram-negative bacteria:
a retrospective analysis. Antimicrob Agents Chemother 2010; 54:1742-8.
5. Diaz-Martin A, Martinez-Gonzales ML, Ferre R, et al. Antibiotic prescription
patterns in the empiric therapy of severe sepsis: combination of antimicrobials
with different mechanisms of action reduces mortality. Crit Care 2012; 16:R223.
6. Paul M, Benuri-Silbier I, Soares-Weiser K, et al. lactam monotherapy versus
lactam-aminolycoside combionation therapy for sepsis in immunocompetent
patients: systematic review and meta-analysis of randomised trials. BMJ 2004;
328:668-72.
7. Safdar N, Handelsman J, Maki DG. Does combination antimicrobial therapy
reduce mortality in Gram-neative bacteraemia? A meta-analysis. Lancet Infect
Dis 2004; 4:519-27.
281
15.3.

,
,
, . () , .
5%, 7 % (1). 25% -, 80% (CRBI,
engl. catheter related blood infection), (VAP, engl. ventilator associated pneumonia)
(CAUTI, engl catheter
associated urinary tract infection).

CRBI 5% 26%
(2) 3% 20% (3).
,
.
, 10-1000 .

,
, .
.
. , ,
, .
(-, ) (4).

282
15.
. .

. 2
.

,
.

,
. ,
.
1, 2 3 , ,

- 2002. 2006. .
1. ()

(%)
0-28
122
151 (42.9)
1 12
59
65 (18.5)
1 6
51
61 (17.3)
6 12
28
30 (8.5)
12 18
40
45 (12.8)
300
352 (100)
2.
()
(%)
15 (4,3)
19 (5,4)
14 (4,0)
3 (0,9)
13 (3,7)
2 (0,6)
66 (18,8)
283
3.
Staphylococcus aureus
Koagulaza Staphylococcus
Candida albicans
Klebsiella pneumoniae
Staphylococcus epidermidis
14

- : ,
. ,
(5). , , , ,
. ,
.
.
30-450. . .
H2 ,
(6).
, . .
.
.
284
15.

, .
, .
15% 30 90% 30
(7). CAUTI , (8, 9).
, , .
. ,
25% 2 .
.
, ,
.
, .
.
, .
1. Gastmeier et al. Converting incidence and prevalence data of nosocomial

infections: results from eight hospitals. ICHE 2001; 22:31-4
2. McGee DC, Gould MK. Preventing complications of central venous catheterization.
N Engl J Med 2003; 348:1123-33.
3. Citak A, Karabocuolu M, Ucsel R, et al. Central venous catheters in pediatric patients
subclavian venous approach as the first choice. Pediatr Int 2002; 44:83-6.
285
4. Maki DG, Ringer M, Alvarado CJ. Prospective randomised trial of povidoneiodine, alcohol, and chlorhexidine for prevention of infection associated with
central venous and arterial catheters. Lancet 1991; 338:339-43.
5. Kaye J, Ashline V, Erickson D, et al. Critical care bug team: a multidisciplinary
team approach to reducing ventilator-associated pneumonia. Am J Infect Control
2000; 28:197-201.
6. Erhart LM, Rangel MC, Lu PJ, et al. Prevalence and characteristics of children
at increased risk for complications from influenza, United States, 2000. J Pediatr
2004; 144:191-5.
7. Warren JW. Nosocomial urinary tract infections. In: Mandell GL, Bennett JE,
Dolin R. (editors). Principals and practices of infectious diseases, 5th ed.,
Churchill Livingstone, Philadelphia, 2000; 328-39.
8. BoyceJM,PittetD.Guidelineforhandhygieneinhealth-caresettings.Recommendations
of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/
SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology
of America/Association for Professionals in Infection Control/Infectious Diseases
Society of America. MMWR Morb Mortal Wkly Rep 2002; 51:145.
9. Guideline for Prevention of Catheter-associated Urinary Tract Infections 2009.
Carolyn V. Gould, MD, MSCR; Craig A. Umscheid, MD, MSCE; Rajender K.
Agarwal, MD, MPH; Gretchen Kuntz, MSW, MSLIS; David A. Pegues, MD and
the Healthcare Infection Control Practices Advisory Committee (HICPAC).
286
15.
15.4. ,

, ,

, 15-20% , 5%
.
30-35% .

(4-5
), , (15
) (
). 800.000 , 270.000 (
, ).
.

Staphylococcus aureus-
Staphylococcus aureus . Staphylococcus
aureus : , ,
, . Staphylococcus aureus , , ,
.

.
. , Fc IgG
. 8 IgG ,
. , 1 ( ) .
287
, II T-.
( )
. -
.
, , -, -,
.
E
10 50% , 250
. 85%
, 15% (1). 12 .
. . , 80/81 50- 60- , .
.
(Meticillin Resistent Staphylococcus Aureus -MRSA).
MRSA
(Epidemic MRSA EMRSA) (2).

Staphylococcus aureus- o
(Toxic Shock Syndrome - TSS) TSST-1 Staphylococcus aureus. TSS
1980.
( ).
, , ,
, .
.
288
15.
TSS
, .
. . .
,
- .
, .
, .
,
.
, (
), , , . , 25%
.
( )
, , ,
.
. Streptococcus- , Staphylococcus-om je
. , , .
3 5
, , ,
, , , (). , , , , . ,
- ().
289
5
.
,
. , .
, , 20-42%.
, - , .
,
-. .
. . (
). , .

:
, .
.
.
,

(Tumor Necrosis Factor TNF) - . . . , PRISM - Pediatric
Risk of Mortality, P-MODS - Pediatric Multiple Organ Dysfunction Score PELOD
Score -Pediatric Logistic Organ Dysfunction, ,
CRIB I CRIB II -Clinical Risk Index for Babies), GMSPS Score - Glasgow
Meningococcal Septicaemia Prognostic Score, Rotterdam Score - Meningococcal
Septic Shock in Ghildren, Paediatric Coma Scale- PCS.
95% Staphylococcus aureus- -.
290
15.
- .
, Mec A enicillin binding protein 2A (PBP2A)
- (, )
. Staphylococcus
aureus- ( 8g/).
.
, Staphylococcus aureus , ,
. - ,
.
. ,

. ,
, , (3).
Staphylococcus aureus- .
. / .
. (4).
20-40 g/,
10 g/. 4-8 g/,
2 g/ (5).
Staphylococcus aureus- ,
,
. 15 / 6-12 , ,
. ()
, , . ,

, . 4 /
(6).
291
1. Milstone AM, Song X, Coffin S, et al. Identification and eradication of methicillinresistant Staphylococcus aureus colonization in the neonatal intensive care unit:
results of a national survey.Infect Control Hosp Epidemiol 2010; 31:766-8.
2. Abdel-Haq N, Quezada M, Asmar BI. Retropharyngeal Abscess in Children: The
Rising Incidence of Methicillin-Resistant Staphylococcus aureus.Pediatr Infect
Dis 2012; 31:696-9.
3. Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious
Diseases Society of America for the Treatment of Methicillin-Resistant
Staphylococcus Aureus Infections in Adults and Children.Clin Infect Dis 2011;
52:e18-e55
4. McNamara D. Vancomycin dosing nomograms inadequate for tweens and
teens. Medscape Medical News http://www.medscape.org/viewarticle/818576.
Accessed January 20, 2014.
5. Gillon JE, Cassat JE, Di Pentima MC. Validation of two vancomycin nomograms
in patients 10 years of age and older.J Clin Pharmacol 2014; 54:35-8.
6. Lane JW, Tang J, Taggard D, et al. Successful use of daptomycin and linezolid,
without surgical intervention, in the treatment of extensive epidural abscess and
bacteremia due to methicillin-resistant Staphylococcus aureus (MRSA). Infect
Dis Clin Pract 2011; 19:362-4.
292
16.

:
.
:
.
16.
16.1.

,
,
,
,
,
, ,
, ( , ),
(1).

(2). ,
.
, , ,
. . ,
.
doppler , doppler . 90%, (50-92%). , , , ,
, ,
.
, .

- , ,
, -
( , , ), () ;
, , ,

.
295

, ,
,
.
.
,
.
(3).

real-time,

.
3,5 5 Hz.
,
.
(4).

a (Puylaert) 1986. .

(5).
,
(6).
, .
,
. ,
, ,
. ,
, , .

. ,

.
6, 8 .
.
296
16.

. ,
, .

.
.
, .

;
(7).

()
.
. , 8
.
.
.

. 7 .
(1,000) (0,941) (8,9).

.
2 ,
.

. , ,
.
297
.
.

()
.
.

,

.
,
, ,
.

.

.

.
,
.

, .

.

, .
, .

.
298
16.

.

.
6 .
( 1). (10). ,
, : ,
, .
.
.
1.

( )
, .
II
III
IV

,

.
, . ,
, .

.
,
. , Applegates

(11).
299

,
.
1. . .
1996; 49:487-90.
2. , , , . . , 2009; LXII (11-12):597-602.
3. , , . . , , 2012.
4. . : . , , 2007.
5. Puylaert JBCM. Acute appendicitis: US evaluation using graded compression.
Radiology 1986; 355:60.
6. .
. , , 1996.
7. Douglas CD, Macpherson NE, Davidson PM, et al. Randomised controlled trial
of ultrasonography in diagnosis of acute appendicitis, incorporating Alvarado
score. Br Med J 2000; 321:919-22.
8. Grebeldinger S, Radoji B, Meljnikov I, et al. The news in ultrasound diagnostic
of acute appendicitis in pediatric patients. HealthMED 2010; 4:964-72.
9. Radoji B, Grebeldinger S, Cigi T, et al. Diagnostic scores in acute appendicitis
with prospective evaluation of Neoplanta score in pediatric patients. HealthMED
2011; 5:2163-76.
10. Kaneko K, Tsuda M. Ultrasoundbased Decision Making in The Treatment of
Acute Appendicitis in Children. J Ped Surg 2004; 39:1316-20.
11. Applegate KE, Sivit CJ, Salvator AE, et al. Effect of cross-sectional imaging on
negative appendectomy and perforation rates in children. Radiology 2001;
220:103-7.
300
16.
16.2. -

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

.
( )
, . . , ,
,
, ,
. , , , ( // ).
,
. : , - , .
301
, ,
, ( ,
.).
,

.
, ( ) .

1. 30 mm - - (),
.
2. 30 mm
. .
3. 10-30 mm ,
. 10-30 mm, , 30 mm
.
4.
, :
- 7 mm;
MAG-3 renal scan
, . :
-- , ;
-- (15-30 ) , ()
:
-- 35% - ;.
-- 35-45 % - 3 ;
-- 45% - 6 .
302
16.

.
, , :
1. 10 mm 10% .
2. 15 mm - 40% .
3. 20 mm - 80% .
.

.

o : (2microglobulin, N-aceyl--glucosaminidase ),
, .
.
1. Garne E, Loane M, Wellesley D, et al. Eurocat Working Group. Congenitalhydronep

hrosis:prenatal diagnosisand epidemiology in Europe. J Pediatr Urol2009; 5:47-52.
2. Piepsz A,Gordon I,Brock J,et al. Round table on the management of renal pelvic
dilatation in children. J Pediatr Urol2009; 5:437-44.
3. Zareba P, Lorenzo AJ, Braga LH. Risk factors for febrile urinary tract infection
in infants withprenatalhydronephrosis: comprehensive single center analysis. J
Urol 2014; 191:1614-9.
4. Ismaili K, Piepsz A. The antenatally detected pelvi-ureteric junction stenosis: advances
in renography and strategy of management. Pediatr Radiol 2013; 43:428-35.
5. Ransford G, Young E, Castellan M, et al. Renal pelvis rupture in a kidney with
ureteropelvic junction obstruction and extrarenal calyces. J Pediatr Urol 2013;
9:27-30.
303
16.3. .
?

,
,

, Jean-Martin Sharcot, Duchenne- , 1878. . 1893. Londe, Sharcot- ,
La Photographie medicale (1). . , ,
, . .

,
(2). ,
. , . , (3).
, .
? (3).
.

,
.
, ,
, . , , .
,
. . ,
, .
304
16.

. .
.

,
.
, . , . .
.

. () , , , .
, , . ,
(3).
The General medical council
,
, , (4).

.
? ,
(androgen insensitivity syndrome, AIS),
, .
,
, ,
, (3). 46,XY (complete AIS)
,
. ,
, , .
305

,
(3).

.
.
.
?
? .

, .

The General medical
council, Institute of Medical Ilustrations International Committee of Medical Journal
Editors (5).
, .
:
1. ;
2.
;
3. ;
4. ;
5. ;
6. , ( ) ;
7. ,
;
8.
. ;
9. ;
306
16.
10.
;
11.
;
12. .
.

, ,
. .
(6)
________________________________________________________
_______________________
-
____________________________________________________________________
, , ( ) . ,
, . . .

____________________________ . ________________________
.
1. ,
, . . ,
. .
____________________________ ____________________________
2. ,
:
____________________________ ____________________________
3. :
____________________________ ____________________________
307
1. Medical photography. http://en.wikipedia.org/w/index.php?

2. Krsti ZD, Perovi S, Radmanovi S, et al. Surgical treatment of intersex disorders.
J Ped Surg 1995:30:1273-81.
3. Creighton S, Alderson J, Brown S, et al. Medical photography: ethics, consent and
the intersex patients. BJU Int 2002; 89:67-72.
4. The general medical Council. Good Medical Practice, 2nd ed. July 1998.
5. International Committee of Medical Journal Editors. Uniform requirement for
manuscripts submitted to biomedical journals. JAMA 1997; 277:927-34.
6. Cunniff C, Byrne JLB, Hudgins LM, et al. Informed consent for medical
photographs. Genet Med 2000; 2:353-5.
308
16.
16.4.

?

,
,

, , , .
, ,
.
.
, , .

() 0,5% 1% .

(1,2).
,
( , ) (
, ).
, (2).
309

.

, , , . .
,

, . .

, (
, ). . single gene , :
(Edwards syndrome), T (Turner syndrome),
(diGeorge syndrome), (Noonan syndrome), (Williams
syndrome), (Holt Oram syndrome), (CHARGE
syndrome), (Pierre Robin syndrome), (Marphan
syndrome) .
. , - (75% ) (3). ( ,
) , .
.
, , .
(), , , ,
, , (4).
310
16.

(1, 2): , ,
, ,
, , ,

, /, / , , , , .
, , , , .
. .
,
. , , , .
,
, .
, , , , , .
.
:
, , , ,
, .

,
, , , .
/ .
311

,
,

/
.
,
. . , 24
48 , .

. 1 ()
( ), , .
.

, ( )
.

, .

. , , . ,
.
,
. ,
, .

312
16.
. , .
in utero. , , . .
, . .
.
,

. ,
.
,

.

.
.

. 40% 50%
( ,
, ).

( ), .

6 (5,6).
(Marfan syndrome).
1 .
.
313
.
35% () 80% ( ).
, .

.

( 18), ( 13).
,
. (Alagille syndrome)
,
, (6).

, , .
10 7%
15% , .
.
,
: , , .
, , (Rubinstein
Taybi syndrome), (Dandy Walker syndrome).
. (Carney complex)
de novo (7). ,
(2% 6%) (2% 5%). (1% 5%).
, , , .

.
(8).
314
16.
: .
( ) .
.
/ . ,
,
. , . . ,
.
. , ,
.
1. Gucer S, Ince T, Kale G, et al. Noncardiac malformations in congenital heart

disease: A retrospective analysis of 305 pediatric autopsies. Turkish J Pediatr
2005; 47:159-66.
2. Miller A, Riehle-Colarusso T, Alverson CJ, et al. Congenital heart defects and
major structural nonacardiac anomalies, Atlanta, Georgia, 1968 to 2005. J Pediatr
2011; 159:70-8.
3. Pierpont ME, Basson CT, Benson DW Jr, et al. American Heart Association
Congenital Cardiac Defects Committee, Council on Cardiovascular Disease
in the Young. Genetic basis for congenital heart defects: current knowledge: a
scientific statement from the American Heart Association Congenital Cardiac
Defects Committee, Council on Cardiovascular Disease in the Young: endorsed
by the American Academy of Pediatrics. Circulation 2007; 115:3015-38.
4. Pierpont ME, Basson CT, Benson Jr DW, et al. Genetic basis for Congenital Heart
Defects: Current Knowledge. Circulation 2007; 115:3015-38.
5. Huhta J, Kersti K. Enviromental origins of congenital heart disease: The heart
placenta connection. Semin Fetal Neonatal Med 2013; 18:245-50.
315
6. Reller MD, Morris CD. Is Downs syndrome a risk for poor outcome after repair
of congenital heart defects. J Pediatr 1998; 132:738-41.
7. Formigiari R, Michielon G, Digillio MC, et al. Genetic syndromes and congenital
heart defects: how is surgical management affected. Eur J Cardiothorac Surg
2009; 35:606-14.
8. Stajevic M, Vukomanovic V, Kuburovic V, et al. Early recurrent left atrial myxoma
in a teenager with de novo mutation of Carney complex. Indian J Hum Genet
2011; 17:108-10.
316
17.
:
.
17.
17.1.

, , ,
,
()
. ,
1/3 3. . 2. 70% . 3.
18. , 6. 11. . , 4. 7. , ,
, . , .
, 268 1000 .
, . , , ,
, ( 80% 40% ) (1,2).
3 . ,
, - .
, 20% , (), , , ,
(). U 25% -

.
, 35%, 25% 15%, .
, ,
3
, 6
12 ,
(15-30% ) (3).
319

,
, , , . /
. .
,
,
, , . , , 50-75%
(3).
/ ,
, .
, .
, ,
,
.
(5).
,
: , , -
.

( ).
320
17.

, , ,
. ,
48-72 , ,
,
,
, (6).
,

.
48-72 , .

, 39
. ,
.
,
, 40-50 // 80-90
//, .
. . 5 10 .
10
, [7].

. -
, , ,
, (. ).
321

, ( )
, .
3 6 4-6
12 - [8].

- . 5
(
), 5
.
, , , , , ,
( , ,
, .)
1. Liese , Carmona , Cantarutti L, et al. Incidence of acute otitis media in young

children seen in European medical practices. 6th World Congress of the World
Society for Pediatric Infectious Diseases, Buenos Aires, Argentina, 1822
November, 2009.
2. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute
respiratory tract infections in US ambulatory settings. JAMA 2009; 302:75866.
Elizabet B. Medical and surgical strategies for prevention of recurrent otitis.
Strategies for the prevention of recurrent Acute Otitis Media. 2002; 1:10-27.
3. Niemela M, Uhari M, Jounio-Ervasti K, et al. Lck of specific symptomatology in
children with otitis media. Pediatr Infect Dis J 1994; 13:765-8.
322
17.
4. American Academy of Pediatrics and American Academy of Family Physicians.

Diagnosis and management of acute otitis media, Pediatrics 2004; 113:145165.
5. Spiro DM, Tay KY, Arnold DH, et al. Wait-and-see prescription for the treatment
of acute otitis media: a randomized controlled trial. JAMA 2006; 296:123541.
6. Marchisio P, Bellussi L, Mauro DG, et al. Acute otitis media: From diagnosis to
prevention. Summary of the Italian guideline. Int J Pediatr Otorhinolaryngol
2010; 74:120916.
7. , . . , , 2004.
323
17.2.

,
,
,

. 30% 40% .
.

.
.

,
. , .
-
, - , , ,
.
, , ,
. (1).
,
. 140 170. (
) . , 1.
(2), ,
. ,
, .
324
17.
.
.

. : , .
, :
(, , ) - . .
7 8, .
( ) 3 . (3).

. (4).
- , , , ;
(5).
---- ,
:
;
, .
, ,
.
(6).
35% , 40% .
25% (7).
, : ( 35C), ( 35C 37C) ( 40C).
pH.
,
, ,
(8).
325
1. Ahmad M, Dargaud J, Morin A, et al. Functional morphology of phonation

evaluated by dynamic MRI. Surg Radiol Anat 2006; 28:481-5.
2. Crelin ES. Development of Upper Respiratory System. Clinical Symposia CIBA,
1976.
3. Berman JM. Surgical Anatomy of the Larynx. WB Saunders Company,
Philadelphia, 1995.
4. Heyder J. Mechanisms of Aerosol Particle Desposition. Chest 2001; 80:820-3.
5. Hiller J et al. Physical Properties of Therapeutic Aerosols. Chest 2001; 80:901-3.
6. Schafer T, Schnoor M, Wagenmann M, et al. Therapeutic Index (TIX) for
intranasal corticosteroids in the treatment of allergic rhinitis. Rhinology 2011;
49:272-80.
7. Shaw HS, Deliyski DD. Mucosal wave: a normophonic study across visualization
techniques. J Voice 2008; 22:23-33.
8. Stankovi P i sar. Rehabilitacioni tretman disfonija. Acta Clinica 2008; 8:139-42.
326
18.
:
.
18.
18.1.
, ,
,
,
K .
e ( Streptococcus
mutans ) (1). S. mutans
.
,
(2).
3 (3). ,
, ,
. , , ,
(3, 4). ,
, . .
(4).
, , .
.
, 8,3% (5).
,
, .

. , , (1).
: , , ,
, , ,
329
, ,
(1).
. ,
.
(),
( )
72 . 3
.
(Severe early childhood caries SECC),
, (
):
<3 - ;
3 5 - , ,
,
( ) 4,5
6 3 5 .

69,7% , 8,3% (5).
5% () 55% ( ) (3).
.
(6). S. mutans
Streptococcus sorbinus .
,
, .
, S. mutans 30%
. S. mutans,
, (1).
, ,
. ( ), /
( ) . .
330
18.
,
. , ,
(3, 7).

.
. ,
. .
.
(white spot lesion), ,
, .
. ,
.
,
.
, (
) , .
, .
.

, .
e
a , .
:
1. . .
331
, ,
2.
, ,
.
3. .
:
-- ;
-- ;
-- ,
12. 14. ;
-- ;
--
.
4. .
,
1. (1, 8).
1.
(ppmF)*
0,3
0,3 0,6
0.6
6 3 .
0,25 mg
0**
0**
3 6 .
0,5 mg
0,25 mg
6 16 .
1 mg
0,25 mg
6 .
*1.0 ppm = 1mg/L i 2.2 mg NaF 1 mg F

** 0,25 mg
merican Dental Association recommendation dosages for fluoride supplementation (3)
2.
(1,8).
2.

a K
6 -
500 ppm
2-6
1000 (+) ppm
>6
1450 ppm
1-2 cm
332
18.
:
1. , (3).
2. . , ,
.
3.
4.
5. 3 6 (3).
:
1.
.
2.
, .
3.
, . ,
, (2,3).

,
,
.
1. Colak H, Dulgergil C, Dalli M, et all. Early chilhood caries update: A review of

causes, diagnoses and treatments. J Nat Sci Biol Med 2013; 4:29-38.
2. Douglass JM, Douglass AB, Silk HJ. A practical guide to infant oral health. Am
Fam Physician 2004; 70:2113-20.
3. Duggal M, Camerun A, Toumba J. Early chilhood caries. In: Duggal M, (editor).
Paediatric Dentistry at a Glance. Blackwell, Oxford, 2013; 40-1.
333
, ,
4. Grindefjord M, Dahllof G, Modeer T. Caries development in children from 2.5 to

3.5 years of age: A longitudinal study. Caries Res 1955; 29-449-54.
5. Ivanovi M, Carevi M, Markovi D. Program preventivne stomatoloke zatite
dece i omladine. Stom Glas Srb 2010;57:36-44.
6. Berkowitz RJ. Causes, tratment and prevention of early chilhood caries: A
microbiologic perspective. J Can Dent Assoc 2003; 69:304-7.
7. Tuek I, Carevi M, Tuek J. The presence of early childhood caries among the
members of different ethnic groups of the South Backa District. Vojnosanit Pregl
2012; 69:104651.
8. Ivanovi M, Carevi M, Markovi D i sar. Protokol za primenu fluorida. U:
Ivanovi M (urednik). Protokoli u stomatologiji. Stomatoloki fakultet, Beograd,
2009; 22-47.
334
18.
18.2.
,
,

. , .
, (),
(). (, )
: (
), ( ), ( ) (1).
.

, ( )
. ,
.
, .
, ,
,
(2-4).
,
.
,
(3-6).
0,3 3,8% ,
. , 80% ,
.

( , ,
335
, .).

(3-6).
, , ( ).
( ).
,
. ,
.
, ,
.
(- )
. .
. ,
( ) ,
.
.
.
, (
). ,

(3, 5).
.
,
. . .

(3, 5, 6).
,
.
. ,
. ,
. , ,
336
18.
, .
,
, .
, ,
.
(3, 5).

, .

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

, , .
,
, , . , , ,
.
, .
, .
, .

. .
, .
, , : , , , , .
337
,
, 6-12 ,
. ,
,
. ,

, .

.
, , . ,
, . . ( ).
,
,
,
(3, 7).
1. Russell , Folwarczana . siodens - diagnosis and managament of

common supernumeraru. Can Dent Assoc 2003; 69:362-6.
2. Meechan JG. Oral pathology and oral surgery In: Welbury R (editor). Pediatric
Dentistry. Oxford University Press, Hong Kong, 2001; 337-69.
3. Vulievi Z. Mandi J. Oralno hirurke intervencije u dece. U: Dragan Beloica D i
sar. Deja stomatologija praktikum. Kua tampe, Beograd, 2010; 193-210.
4. Koch G. Oral mucous lesions and minor oral surgery. In: Koch G, (editor).
Pediatric Dentstry a Clinical Approach. Wiley-Blackwell, Oxford, 2009; 298-308.
5. Troulis M. Dentoalveolar surgery. In: Kaban L (editor). Pediatric Oral and
Maxilofacial Surgery. Saunders, Philadelphia, 2004; 125-45.
6. Brand , khavan , ng H. Orthodontic, genetic and periodontal
considerations in the treatment of impacted maxilary central incisors: study of
twins. m rthod Dentofacial Othop 2000; 117:68-74.
7. Mandi J, Kosanovi D. Diagnosis and managament of nonerupted mesiodens.19th
Congress of the Balcan Stomatological Society, Belgarde, 2014.
338
XVII

4Upharma
Abbott
Abbvie Biopharmaceuticals
Alca trgovina - HIPP
ALPEN PHARMA
Berlin Chemie
Bonifar
Ceumed Pharma
ERBA GREEN
Ferring
Formasana
Galenika
INPHARM
Ivani i sinovi
Jadran Galenski Laboratorij
Johnson & Johnson
KIBID
Laboratorie Innotech
LIFE MEDIC
MEDTRONIC
MSF Pharm
Nelt Co
Nestle
Novo Nordisk
Oktal Pharma
Pfizer
Pharmaswiss
Pretti Organica
SALVEO
Sanofi
SHIRE & SOLPHARM Adriatic
Stiga Novi Sad
Zeleni izbor
CIP -
,
616-053.2(082)
. (17 ;
2014 ; )
/
, XVII , 8. 14.
2014, , ; [
,
]. - :
, 2014 ( :
). - XXIII, 338 . : . ; 24
cm
600. - .
ISBN 978-86-85527-16-6
a) -
COBISS.SR-ID 207618060

Xvii Pedijatrijska Skola Zbornik Radova

Uploaded by

Copyright:

Available Formats

You might also like

Xvii Pedijatrijska Skola Zbornik Radova

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Xvii Pedijatrijska Skola Zbornik Radova

Uploaded by

Copyright:

Available Formats

XVII

7.3. ............... 121

10. .......................................................................................... 175

13.4. ......................................................................................... 240

16.3. . ?.................. 304

2006. 6,5/1000 2015. (5,6).

1. Committee on Perinatal Health. Toward Improving the Outcome of Pregnancy:

1. Heard E, Martienssen RA. Transgenerational Epigenetic Inheritance: Myths and

3. Soon WW, Hariharan M, Snyder MP. High-throughput sequencing for biology

1. Alfadhel , Thihli KA, Moubayed H, et al. Drug treatment of inborn errors of

PH2 PH3. AGXT, GRHPR HOGA.

1. Kokorowski PJ, Hubert K, Nelson CP. Evaluation of pediatric nephrolithiasis.

6. Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med 2013; 369:649-58.

1. Gomella T. TORCH infections (Toxoplasmosis, Rubella, Cytomegalovirus and Herpes

1. Saharan , Lodha , Agarwal , et al. AIIMS- NICU protocols 2010. Perinatal

1. Schurgin OKeeffe G, Clarke-Pearson K. Council on Communication and Media,

1. Shrier LA. Sexually Transmitted Infections: Chlamydia, Gonorrhoea, Pelvic

LTT (<20 mg/dl)

1. Naim HY, Zimmer KP. Geneically deermined disaccharidase deficiency. In:

4. Mc Millen IC, Robinson JS. Developmental origins of the metabolic syndrome:

8. os AP, MRabet L, Stahl B, et al. Immunemodulatory effects and potential

NEC: ; HUS: - ; GERD:

1. Cadranel S, Scaillon M. Approach to gastrointestinal bleeding. In: Guandalini

richuris trichiura 90%. , ,

7. Harhay M O, Horton J, Olliaro PL. et al. Epidemiology and control of human

1. Mieli-Vergani G, Heller S, Jara P, et al. Autoimmune hepatitis. J Pediatr

8.1. EVALUATION AND OUTCOME OF CHRONIC WET

Protracted Bacterial Bronchitis and Bronchiectasis

Chronic wet cough evaluation

(Child Health Qestionnaire CHQ).

(Pediatric Asthma Quality of Life Questionnare PAQLQ)

1. Bullinger M, Anderson R, Cella D. Developing and evaluating cross cultural

1. Palange P, Ward S, Carlsen K-H, et al. Recommendations on the use of exercise

1. Palinski W and Napoli C. Impaired Fetal Growth, Cardiovascular Disease, and

5. Varan B, Tokel K, Yilmaz G. Malnutrition and growth failure in cyanotic and

1979. (1) 15-50 . .

, funny current ili If (3).

1. Bauernfeind RA, Amat-Y-Leon F, Dhingra RC, et al. Chronic nonparoxysmal sinus

Dolk i Loane 2009**

( 85%) PKD1 16p13.3, 15% PKD2 4q21

1. Wilson PD. Polycystic kidney disease. N Engl J Med 2004; 350:151-64.

NFC2/, NFC 1, 4, 5, 6, 7, 8, 9, 11 NFC3. NPHP1

1. Salomon R, Saunier S, Niaudet P. Nephronophthisis. Pediatr Nephrol 2009;

BardetBiedl , Alstrm , Jeune , Ellis van Creveldov , Sensenbrenner ) . , (4).

1. Gascue C, Katsanis N, Badano JL.Cystic diseases of the kidney: ciliary dysfunction

1. The international classification of headache disorders, 3rd ed. Cephalalgia 2013;

4. Abu-Arafeh I, Russell G. Paroxysmal vertigo as a migraine equivalent in children:

1. Chiu S. Pediatric sleep disorders. Dostupno na : http://emedicine.medscape.com/

1. Fiedman N, Ghosh D, Moodley M. Syncope and paroxysmal disorders other theb

SC- -1, -1 (IL-1). IL-1

1. Hashkes PJ, Toker O. Autoinflammatory sydromes. Pediatr Clin North Am 2012;

1. Hong T. Approach to abdominal mass. Dostupno na: http://learnpediatrics.com/

1. Papaioannou G, Kieran McH. Neuroblastoma in childhood: review and

(17,4 %) , (8,7 %).

1. Gatta G, Botta L, Rossi S, et al; EUROCARE Working Group. Childhood cancer

1. Gobel U, Schneider DT, Calaminus G, et al: Germ-cell tumors in childhood and

(80% 44%), (3%

1. The Diabetes Control and Complications Trial Research Group. Effect of

8. Plank J, Bodenlenz M, Sinner F, et al. A double-blind, randomized, dose-response