You are on page 1of 126

78

2



2015
E E

Paediatriki Volume 78
Number 2
April
May
June
2015
Trimonthly publication of the Greek Paediatric Society
150


78 | 2 | A - - 2015

.



. .

E E M
.
.
.
.
.

.
. K-
.
. -
.
.

154 .
. -
. -

158
-
Jones .

, ,

166


, , ,

176
: sexualization
. , .

188

. ,

202
:
,

220

E 15 :
ADONUT
, , , -
, & ADONUT
151

234
e-mail: grammateia@e-child.gr

:
http://e-child.gr/publications/ , , , ,
instructions-to-authors

246
I
E E
15,15451, . - . -

T.: 2107771140
e-mail: grammateia@e-child.gr , , ,

256
E : 40
E, : 20
-
deferasirox
, , , ,
, , ,

266
score

, , - ,

152

Paediatriki
Volume 78 | Number 2 | April - May - June 2015
President
A. Constantopoulos

Editorial board
Director
G. S. Varlamis

Trimonthly publication of the Greek Paediatric Society Members


S. Andronikou
E. Galanakis
A. Evangeliou
L. Thomaidou
M. Kanariou

Contents A. Kapogiannis
S. Kitsiou-Tzeli
E. Mantadakis
P. Panagiotopoulou-Gartagani
A. Papadopoulou
V. Papaevagelou

154 A. Papathanassiou
A. Siamopoulou-Mavridou
SHORT ABSTRACTS A. Syrigou-Papavasiliou

158
STATE OF THE ART - REVIEW ARTICLE
Revision of the jones criteria for the diagnosis of acute rheumatic fever. The contribution of
the widespread use of echocardiography
Maria Gogou, Anastasia Keivanidou, Andreas Giannopoulos

166
REVIEW ARTICLES
Genetic predisposition and personalized nutritional intervention for childhood obesity
Kalliopi Gkouskou, Anastasia Markaki, Theodosios Theodosiou, Aristides Eliopoulos

176
Sexualization of children and adolescents
A. Tsitsika, V. Dimitrakopoulou

188
Growing pains
Maria N. Vasilopoulou, Maria Tsolia

202
Ciliopathies: The central role of primary cilia in a wide disease spectrum
Stavroula Psoni, Helena Fryssira

220
ORIGINAL ARTICLES
Prevalence of simple and abdominal obesity among 15 year old adolescents in Greece: results
from the ADONUT study
Maria Grammatikopoulou, Dimitrios Poulimeneas, Konstantina Gerothanasi, Efstratios Kiranas,
Maria Tsigga & ADONUT Study Group
153

Manuscript submission 234


e-mail: grammateia@e-child.gr Early changes of amino acids in critical ill children dependent on disease severity
Theonymfi Tavladaki, Anna Maria Spanaki, Helen Dimitriou, EvaggelosPapakonstantinou, George
Instructions to authors:
http://e-child.gr/publications/ Briassoulis
instructions-to-authors

Owner 246
Greek Paediatric Society Networks of primary care and welfare for deaf primary school children.
15, Mpakopoulou st. Parents satisfaction
GR - 15451, . Psychiko
Tel.: +302107771140 Bredaki Maria, Ktena Danai, Barbouni Anastasia, Kornarou Eleni
e-mail: grammateia@e-child.gr

Annual subscription 256


All foreign countries: US$50 Relapse And Effective Prevention Of Complications of Secondary Hemosiderosis with
Iron Chelation With Deferasirox In Childhood Malignancies
icaela Nicolaou, Yiouli P. Ktena, Archontis Zampogiannis, Anastasia Athanasiadou, Spiros Vlaho-
poulos, George Lambrou, Maria Adamaki, Maria Moschovi

266
prospective evaluation new scoring system for diagnosis of acute appendicitis in children
Adelais Tzortzopoulou, Panagiota Giamarelou, Aikaterini Michail-Strantzia, Alexandros Passalidis
154

-
Jones .

, ,
,
,
.

Jones. .


-

, , ,
,

. , , 24
, .

: sexualization
. , .
, -
,
.
,
, .

. ,
,
.
. ,
, ,
.

.
:
,


.
-
- ,
155

SHORT
ABSTRACTS

.
.


E 15 :
ADONUT
, , ,
, & ADONUT
.
, ,
,
. .
,
.


15 .


, , , ,


, ,
.


< 18 .
.
- . -

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

deferasirox
, , , ,
, , ,

156

.
,
.
.

deferasirox .
score

, , - , -

-
9 ,

.

, -
, , ,
/ , , , -
.


1.800.000 ,
, , -

,
.1 -
-
, -
, , , . 1
,
.1 -
-
-
3 ,
, , .5
- .
, , - - -
.2 .
.
6 (
100 : )7 ,8
(%)

- ,
80
-
,
-
, -
, ,
60 -
(1,6 )
. , -

40 33.4
,
30.1 29.1 .5
,9
20 14.8 ,10
11.1
7.8 -

0 , -

1 2 3
.7 ,

-
White-Traut, et al. 2002 5 .
,
%

- 10%
6.2% , -
, -

5% 3%
. -
- 0%
0% .

-1%
, -2%
-5%
3,4
-10%
2 3
,5
3 ,

- Mindell, et al. 2009

.6

:
1. Eliot L. Whats Going On in There? How the Brain and Mind Develop in the First Five Years of Life. New York, NY: Bantam Books; 1999. 2. UNICEF/World Health Organization. Integrating Early Childhood Development (ECD) Activities
Into Nutrition Programmes in Emergencies. Why, What and How [guidance note]. 2014:1-16. 3. Hernandez-Reif M, Diego M, Field T. Preterm infants show reduced stress behaviors and activity after 5 days of massage therapy. Infant
Behav Dev. 2007;30(4):557-561. 4. White-Traut RC, Schwertz D, McFarlin B, Kogan J. Salivary cortisol and behavioral state responses of healthy newborn infants to tactile-only and multisensory interventions. J Obstet Gynecol Neonatal
Nurs. 2009;38:22-34. 5. Mindell JA, Telofski LS, Wiegand B, Kurtz ES. A nightly bedtime routine: impact on sleep in young children and maternal mood. Sleep. 2009;32(5):599-606. 6. White-Traut RC, Nelson MN, Silvestri JM, et al.
Effect of auditory, tactile, visual, and vestibular intervention on length of stay, alertness, and feeding progression in preterm infants. Dev Med Child Neurol. 2002;44:91-97. 7. Field T, Cullen C, Largie S, Diego M, Schanberg S, Kuhn C.
Lavender bath oil reduces stress and crying and enhances sleep in very young infants. Early Hum Dev. 2008;84(6):399-401. 8. Farroni T, Csibra G, Simion F, Johnson MH. Eye contact detection in humans from birth. Proc Natl Acad
Sci U S A. 2002;99(14):9602-9605. 9. Herz RS. A naturalistic analysis of autobiographical memories triggered by olfactory visual and auditory stimuli. Chem Senses. 2004;29(3):217-224. 10. Sullivan RM, Toubas P. Clinical usefulness
of maternal odor in newborns: soothing and feeding preparatory responses. Biol Neonate. 1998;74(6):402-408.

Johnson & Johnson Consumer Companies, Inc. 2015


-

158

Jones A

44,
60100,
e-mail: mariaangogou@

. - gmail.com

-

, ,


,

. , -

. 2015 American Heart Asso-
ciation Jones
-
.

: , ,





, -

..., ....

REVIEW ARTICLES

159

Correspondence
aria Gogou
Revision of the jones criteria for the
Dimitriou Nika 44, 60100,
aterini
e-mail: mariaangogou@
diagnosis of acute rheumatic fever.
gmail.com
The contribution of the widespread
use of echocardiography
Maria Gogou, Anastasia Keivanidou, Andreas Giannopoulos

Abstract
Although rheumatic fever has declined in incidence over the past decades, this disease remains an
important cause of acquired cardiovascular morbidity in childhood and presents a very dispro-
portionate geographic distribution. Besides, the increasing use of cardiac ultrasound has revealed
subclinical carditis in many cases of children diagnosed with rheumatic fever without clinical
findings of carditis. On this basis, in 2015 the American Heart Associations Council on Car-
diovascular Disease in the Young and its Rheumatic Fever, Endocarditis and Kawasaki Disease
Committee revised the classical Jones criteria for the diagnosis of Rheumatic Fever defining
populations as low-risk or moderate-/high-risk and including Doppler echocardiography find-
ings of carditis in major criteria.

Keywords: rheumatic fever, revised criteria, subclinical carditis




. ,
Kawasaki
(1).
, ,
.
Jones American Heart Association 2015
Jones, ,

Maria Gogou .
Anastasia Keivanidou
Andreas Giannopoulos
Unit for Pediatric Cardiol- Jones:
ogy, 2nd Department Jones
of Pediatrics, Aristotle . 1944. -
University of Thessalon- 1992 2000 American Heart
iki, University General
Association, 2001
Hospital of Thessaloniki
AHEPA (2,3).

: : 1. 2. 3.
4. 5. : 1. ( >38,5o C,
) 2. ( PR , ...60mm, CRP3mg/
dl). 2 1 2
(
, ,
). , ,
Jones

160

, 2
.
(4).


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

, <2 100.000 5-14
. ,
.
, ,
,
(153-380
100.000 5-14 )(6,7). ,
,
, 2012

(-- ),

(8).

.
.
,
(, ) 16%-18%
(9). , Meri-
no . (1991) Kocak . (2000)
/ ,
(10,11).

.
,

. ,

,
(12).

: , ,
,
, . ,

(13).
25
,
161

. 1994-
2013 22 786 .
0% ( 1 ) 53%(14-
37). American Heart Association
Doppler
,
(12).


2015 1(12).
:
i) -
( , )

ii)
.

.
iii) ...

iv) ( /
) ,
.
v) .
vi) 3 .

Jones


.
,
.

1: A Jones (American Heart Association, 2015) -


. 2
1 2 , 2 1
2 3

1. ( / )* 1. ( / )*

2. 2. **

3. 3.

4. 4.

5. 5.
Jones

162

1: A Jones (American Heart Association, 2015) -


. 2
1 2 , 2 1
2 3

1. ** 1. **

2. 38,5 C 2. 38 C

3. ...60mm 1 / CRP3mg/dl 3. ...30mm 1 / CRP3mg/dl

4. PR 4. PR

*
.

**
.


1. Seckeler MD, Hoke TR. The worldwide epidemiology of acute rheumatic fever and rheu-
matic heart disease. Clin Epidemiol 2011, 3:67-84
2. Ferrieri P; Jones Criteria Working Group. Proceedings of the Jones Criteria workshop. Cir-
culation 2002, 106:2521-3
3. Dajani AS, Ayoub E, Bierman FZ, Bisno AL, Denny FW, Durack DT, et al. Special Writ-
ing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the
Council on Cardiovascular Disease in the Young of the American Heart Association. Guidelines
for the diagnosis of rheumatic fever: Jones criteria, 1992 update [published correction appears in
JAMA. 1993 ,269:476]. JAMA. 1992, 268:206973
4. Burke RJ, Chang C. Diagnostic criteria of acute rheumatic fever. Autoimmun Rev 2014,
13:503-7
5. Markowitz M. The decline of rheumatic fever: role of medical intervention: Lewis W. Wan-
namaker Memorial Lecture. J Pediatr 1985, 106:54550
6. Milne RJ, Lennon DR, Stewart JM, Vander Hoorn S, Scuffham PA. Incidence of acute rheu-
matic fever in New Zealand children and youth. J Paediatr Child Health 2012,48:68569145
7. Parnaby MG, Carapetis JR. Rheumatic fever in indigenous Australian children. J Paediatr
Child Health 2010, 46:52733
8. Atatoa-Carr P, Lennon D, Wilson N; New Zealand Rheumatic Fever Guidelines Writing
Group. Rheumatic fever diagnosis, management, and secondary prevention: a New Zealand
guideline. N Z Med J 2008, 121:5969
9. Carapetis JR, Currie BJ. Rheumatic fever in a high incidence population: the importance of
monoarthritis and low grade fever. Arch Dis Child 2001, 85:2237
10. Merino Muoz R, Viota Losada F, Sancho Madrid B, Castro Gussoni C, Garca-Consuegra
Molina J. Rheumatic fever and post-streptococcal arthritis: clinical review. An Esp Pediatr 1991,
35:23942
11.Koak G, Imamolu A, Tutar HE, Atalay S, Trkay S. Poststreptococcal reactive arthritis:
clinical course and outcome in 15 patients. Turk J Pediatr 2000, 42:1014
12. Gewitz MH, Baltimore RS, Tani LY, Sable CA, Shulman ST, Carapetis J, et al. American
Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the
Council on Cardiovascular Disease in the Young. Revision of the jones criteria for the diagnosis
of acute rheumatic Fever in the era of Doppler echocardiography: a scientific statement from the
163

american heart association. Circulation 2015, 131:1806-18


13. Remnyi B, Wilson N, Steer A, Ferreira B, Kado J, Kumar K, et al. World Heart Federation
criteria for echocardiographic diagnosis of rheumatic heart disease: an evidence-based guideline.
Nat Rev Cardiol 2012, 9:297309
14. Vijayalakshmi IB, Vishnuprabhu RO, Chitra N, Rajasri R, Anuradha TV. The efficacy of
echocardiographic criterions for the diagnosis of carditis in acute rheumatic fever. Cardiol Young
2008, 18:58692
15. Ozdemir O, Iik S, Abaci A, Hizli S, Akelma AZ, Kilal FM, et al. Silent enemy in acute
rheumatic fever: subclinical carditis. Turk Kardiyol Dern Ars 2011, 39:416 16. Cann MP,
Sive AA, Norton RE, McBride WJ, Ketheesan N. Clinical presentation of rheumatic fever in an
endemic area. Arch Dis Child 2010, 95:4557
17. Beg A, Sadiq M. Subclinical valvulitis in children with acute rheumatic fever. Pediatr Cardiol
2008, 29:61923
18. Caldas AM, Terreri MT, Moises VA, Silva CM, Len CA, Carvalho AC, et al. What is the
true frequency of carditis in acute rheumatic fever? A PROSPECTIVE clinical and Doppler
blind study of 56 children with up to 60 months of follow-up evaluation. Pediatr Cardiol 2008,
29:104853
19. Rayamajhi A, Sharma D, Shakya U. Clinical, laboratory and echocardiographic profile of
acute rheumatic fever in Nepali children. Ann Trop Paediatr 2007, 27:16977
20. Ozer S, Halliolu O, Ozkutlu S, Celiker A, Alehan D, Karagz T. Childhood acute rheu-
matic fever in Ankara, Turkey. Turk J Pediatr 2005, 47:1204
21.Panamonta M, Chaikitpinyo A, Kaplan EL, Pantongwiriyakul A, Tassniyom S, Sutra S. The
relationship of carditis to the initial attack of Sydenhams chorea. Int J Cardiol 2004, 94:2418
22. Ozkutlu S, Hallioglu O, Ayabakan C. Evaluation of subclinical valvar disease in patients
with rheumatic fever. Cardiol Young 2003, 13:4959
23. Karaaslan S, Demirren S, Oran B, Baysal T, Bapinar O, Uar C. Criteria for judging the
improvement in subclinical rheumatic valvitis. Cardiol Young 2003, 13:5005
24. Khriesat I, Najada A, Al-Hakim F, Abu-Haweleh A. Acute rheumatic fever in Jordanian
children. East Mediterr Health J 2003, 9:9817
25. Lanna CC, Tonelli E, Barros MV, Goulart EM, Mota CC. Subclinical rheumatic valvitis: a
long-term follow-up. Cardiol Young 2003,13:4318
26. Figueroa FE, Fernndez MS, Valds P, Wilson C, Lanas F, Carrin F, et al. Prospective
comparison of clinical and echocardiographic diagnosis of rheumatic carditis: long term follow
up of patients with subclinical disease. Heart 2001, 85:40710
27. Hilrio MO, Andrade JL, Gasparian AB, Carvalho AC, Andrade CT, Len CA. The value
of echocardiography in the diagnosis and followup of rheumatic carditis in children and adoles-
cents: a 2 year prospective study. J Rheumatol 2000, 27:10826
28. Elevli M, Celebi A, Tombul T, Gkalp AS. Cardiac involvement in Sydenhams chorea:
clinical and Doppler echocardiographic findings. Acta Paediatr 1999, 88:10747
29.da Silva CH; Pediatric Committee, Sao Paulo Pediatric Rheumatology Society. Rheumatic
fever: a multicenter study in the state of Sao Paulo. Rev Hosp Clin Fac Med Sao Paolo 1999,
54:8590
30. Minich LL, Tani LY, Pagotto LT, Shaddy RE, Veasy LG. Doppler echocardiography distin-
guishes between physiologic and pathologic silent mitral regurgitation in patients with rheu-
matic fever. Clin Cardiol 1997, 20:9246
31. Hoffman TM, Rhodes LA, Pyles LA, Balian AA, Neal WA, Einzig S. Childhood acute
rheumatic fever: a comparison of recent resurgence areas to cases in West Virginia. W V Med J
1997, 93:2603
32. Vasan RS, Shrivastava S, Vijayakumar M, Narang R, Lister BC, Narula J. Echocardiograph-
ic evaluation of patients with acute rheumatic fever and rheumatic carditis. Circulation 1996,
94:7382
33. Maheu B, Costes P, Lionet P, Kamblock J, Papouin G, Mansourati J, et al. Contribution of
Doppler echocardiography to the diagnosis of the first attack of acute rheumatic fever. Arch Mal
Coeur Vaiss 1995, 88:18339
34. Abernethy M, Bass N, Sharpe N, Grant C, Neutze J, Clarkson P, et al. Doppler echocar-
Jones

164

diography and the early diagnosis of carditis in acute rheumatic fever. Aust N Z J Med 1994,
24:5305
35. Veasy LG, Tani LY, Hill HR. Persistence of acute rheumatic fever in the intermountain area
of the United States. J Pediatr 1994, 124:916
36. Wilson NJ, Voss L, Morreau J, Stewart JM, Lennon D. New Zealand guidelines for the
diagnosis of acute rheumatic fever: small increase in the incidence of definite cases compared to
the America Heart Association Jones criteria. N Z Med J 2013, 126:509
37. Caldas AM, Terreri MT, Moises VA, Silva CM, Carvalho AC, Hilrio MO. The case for
utilizing more strict quantitative Doppler echocardiographic criterions for diagnosis of subclini-
cal rheumatic carditis. Cardiol Young 2007, 17:427
165

166

A
,


4,
e-mail: gkouskoukal@

gmail.com
. 6938055379

, , ,


:

.

- (cost effective)
.
-:
MeSHy ( Statnous) (SNPs),
(CNVs) /
.

.
24
pen-array Real time PCR.
: 50 (68 )

. open-array Real time PCR
.
, , 99%.
:

.


: , , ,


Statnous,
-

REVIEW ARTICLES

167

Correspondence
Kalliopi Gkouskou,
Genetic predisposition and person-
Konstantinou Papadaki 4,
Heraklion Crete
e-mail: gkouskoukal@
alized nutritional intervention for
gmail.com
. +306938055379 childhood obesity
Kalliopi Gkouskou, Anastasia Markaki, Theodosios Theodosiou, Aristides Eliopoulos

Abstract
Introduction: Childhood obesity is a major public health issue especially in Greece where its
prevalence is among the higher in Europe. This review aims to present genetic factors that per-
mit a personalized nutritional intervention as well as the most cost effective technology for the
analysis of these factors.
Methods: MeSHy program (Statnous, Greece) was utilized for a systematic review. Single nu-
cleotide polymorphisms (SNPs), copy number variants (CNVs) and insertions/deletions that are
related to childhood obesity and can determine a specific nutritional intervention were identi-
fied. In addition, a market research permitted the evaluation of the most cost-effective method
for the analysis of these genetic factors. Finally, a pilot study of 24 children was performed for
the initial evaluation of pen-array Real time PCR technology.
Results: Fifty genes (68 genetic factors) allow for the formation of a personalized nutritional
intervention plan that aims to prevent or to treat childhood obesity. Open-array Real time PCR
technology is bloodless, convenient, affordable and reliable for the evaluation of a great number
of genetic factors in a large scale.
Conclusions: A personalized nutritional intervention based on genetic analyses for the preven-
tion or treatment of childhood obesity is feasible with current technology.

Keywords: childhood obesity, genetic factors, personalized interventions



,
Kalliopi Gkouskou
, ,
Aristides Eliopoulos
Embiodiagnostics, Genetic

Predisposition Research (1).
Company ,
(2).
Kalliopi Gkouskou ,
Aristides Eliopoulos
Medical School University .
of Crete, Molecular Biol- ,
ogy Department

Kalliopi Gkouskou
.
Anastasia Markaki 1,
Department of Nutrition .
and Dietetics, TEI of :
Crete ) ,
) ,
Theodosios Theodosiou ,
Statnous, Statistical Con- ) .
sultancy

168

1:

1.

2. :

3.

4.
(1)

1. :

2. (2, 3).

3.
(4)

4.
:
(5).

,
, .


MeSHy
(http://tools.bat.infspire.org/meshy).
Statnous
,
(semantic similarity).

Pub Med (3). ,

Pub Med.
( >1 <-1)
. 870
polymorphism(s), SNP(s) copy number variants
obesity and children Pub Med.
MeSHy 4329 2945 (
3152) >1 <-1
870.
.
( ) ( )
169


(4). ,
rtPCR: Real time Poly- ( 1).
merase Chain Reaction
CNV: copy number 1:
variant PRISMAflowchart
SNP: single nucleotide
polymorphism
Pubmed
(n =870) MeSHy
(n = 4329)



(n =3152)
.


(
screening )
(n = 3152)
( )




(n =2695)





(n =457) screening
(n =337 )


(n = 120)

( -)
(SNPs CNVs)
.
24 -
open-array Real time PCR -

.


50 (68 ) ( 2) -
:
) (5-9)
, (10-14)
) ( )

170

) ,
, .. (bias)

) ( )
, (15-18).

1: 50

1 (copy number variation)

FTO (2 polymorhisms/epigenetic changes)

TMEM18

GNPDA2

MC4R

BDNF

TFAP2B

SEC16B

KCTD15

MTCH2

NEGR

POMC

NRXN3

FAIM2

GPRC5B

SH2B1

FANCL

LRRN6

TNNI3K

MAP2K5

HOXB5

CADM2

PTBP2

NUDT3

FLJ35779

ZNF608

TMEM160

RPL27A
171

OLFM4

APOA5

FABP2

GIPR

IRS1

MCM6(2 polymorphisms)

IL6

PPARGC1A

TAS2R38 (3 polymorphisms)

ACEI/D

SHBG*

PPMIK*

CLOCK*

15q26.1**

APOA5

APOE(2 polymorphisms)

CETP

LPL

NOS3

TCF7L2

Thombophilia panel (10 polymorphisms)

Vitamin D deficiency panel (4 polymorphisms)

-
3:

3:

(6, 7) (8)

(9-11) (12)

(13-16) (17)

(18) (19)

(22)-
(20, 21) D

172


2

MassArray, SNPlex, SNOstream Taqman OpenArray.

2: -
(SNPnumber) (samplesize), (23).

1: QuantStudio 12K
Flex Real-time Open Array
(fine mapping) System & AcuFill Robotic System
(Life Technologies).
real time PCR >99%. Quant Studio PCR
( 1) open Array digital PCR

( 12.000
3 40 )
PCR.

(multiplex PCR) ,
.
Quant Stu-
dio open Array (64 )
insertions/deletions CNVs.
24 open-array real time PCR
24
, mul-
tiplex PCR Life
Technologies (34).

2:

,

. ,

,


(SNPs CNVs)

.
. (
: ) (18) ) )
173

(5).
, ,
,
(SNPs CNVs)
.

() lorcaserin hydrochloride phenteramine/topiramate (4).

,
. ,
.
2,
.

, ( 3),

.

.

, ,
.


1. Dietz WH. Overweight in childhood and adolescence. N Engl J Med. 2004 Feb 26;350(9):855-
7.
2. http://wwwoecdorg/els/health-systems/Obesity-Update-2014pdf.
3. Theodosiou T, Vizirianakis IS, Angelis L, Tsaftaris A, Darzentas N. MeSHy: Mining un-
anticipated PubMed information using frequencies of occurrences and concurrences of MeSH
terms. J Biomed Inform. 2011 Dec;44(6):919-26.
4. Garver WS, Newman SB, Gonzales-Pacheco DM, Castillo JJ, Jelinek D, Heidenreich RA, et
al. The genetics of childhood obesity and interaction with dietary macronutrients. Genes Nutr.
2013 May;8(3):271-87.
5. Heath V. Obesity: Genes and a hearty appetite conspire to increase childhood obesity risk.
Nat Rev Endocrinol. 2014 Apr;10(4):187.
6. Young RP, Hopkins RJ. Genetic risk in childhood obesity: implications for clinical practice.
JAMA Pediatr. 2013 Feb;167(2):196-7.
7. Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, et al. Sugar-sweetened bev-
erages and genetic risk of obesity. N Engl J Med. 2012 Oct 11;367(15):1387-96.
8. Gonzalez JR, Estevez MN, Giralt PS, Caceres A, Perez LM, Gonzalez-Carpio M, et al. Genetic
risk profiles for a childhood with severely overweight. Pediatr Obes. 2014 Aug;9(4):272-80.
9. Domingue BW, Belsky DW, Harris KM, Smolen A, McQueen MB, Boardman JD. Polygenic
risk predicts obesity in both white and black young adults. PLoS One. 2014;9(7):e101596.
10. Ciftdogan DY, Coskun S, Ulman C, Tikiz H. The association of apolipoprotein E polymor-
phism and lipid levels in children with a family history of premature coronary artery disease. J
Clin Lipidol. 2012 Jan-Feb;6(1):81-7.
11. Roth CL, Hinney A, Reinehr T, Schreiner F, Nguyen TT, Muller T, et al. TCF7L2 poly-
3: morphism rs7903146 and predisposition for type 2 diabetes mellitus in obese children. Horm

(A).
Metab Res. 2008 Oct;40(10):713-7.
DNA 12. Korner A, Berndt J, Stumvoll M, Kiess W, Kovacs P. TCF7L2 gene polymorphisms confer
. an increased risk for early impairment of glucose metabolism and increased height in obese chil-
dren. J Clin Endocrinol Metab. 2007 May;92(5):1956-60.


13. Smart MC, Dedoussis G, Louizou E, Yannakoulia M, Drenos F, Papoutsakis C, et al. APOE,
CETP and LPL genes show strong association with lipid levels in Greek children. Nutr Metab
(B) Cardiovasc Dis. 2010 Jan;20(1):26-33.

174

14. Kinik ST, Ozbek N, Yuce M, Yazici AC, Verdi H, Atac FB. PAI-1 gene 4G/5G polymor-
phism, cytokine levels and their relations with metabolic parameters in obese children. Thromb
Haemost. 2008 Feb;99(2):352-6.
15. Micali N, Field AE, Treasure JL, Evans DM. Are obesity risk genes associated with binge
eating in adolescence? Obesity (Silver Spring). 2015 Aug;23(8):1729-36.
16. Zhang D, Li Z, Wang H, Yang M, Liang L, Fu J, et al. Interactions between obesity-
related copy number variants and dietary behaviors in childhood obesity. Nutrients. 2015
Apr;7(4):3054-66.
17. Lv D, Zhang DD, Wang H, Zhang Y, Liang L, Fu JF, et al. Genetic variations in SEC16B,
MC4R, MAP2K5 and KCTD15 were associated with childhood obesity and interacted with
dietary behaviors in Chinese school-age population. Gene. 2015 Apr 15;560(2):149-55.
18. Llewellyn CH, Trzaskowski M, van Jaarsveld CH, Plomin R, Wardle J. Satiety mechanisms
in genetic risk of obesity. JAMA Pediatr. 2014 Apr;168(4):338-44.
19. Wardle J, Carnell S, Haworth CM, Farooqi IS, ORahilly S, Plomin R. Obesity associated
genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab. 2008
Sep;93(9):3640-3.
20. Baum JI, Gray M, Binns A. Breakfasts Higher in Protein Increase Postprandial Energy Ex-
penditure, Increase Fat Oxidation, and Reduce Hunger in Overweight Children from 8 to 12
Years of Age. J Nutr. 2015 Aug 12.
21. Jonsson A, Franks PW. Obesity, FTO gene variant, and energy intake in children. N Engl J
Med. 2009 Apr 9;360(15):1571-2; author reply 2.
22. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN. An obesity-associated FTO
gene variant and increased energy intake in children. N Engl J Med. 2008 Dec 11;359(24):2558-
66.
23. Stutzmann F, Cauchi S, Durand E, Calvacanti-Proenca C, Pigeyre M, Hartikainen AL, et al.
Common genetic variation near MC4R is associated with eating behaviour patterns in European
populations. Int J Obes (Lond). 2009 Mar;33(3):373-8.
24. Scott RA, Bailey ME, Moran CN, Wilson RH, Fuku N, Tanaka M, et al. FTO genotype and
adiposity in children: physical activity levels influence the effect of the risk genotype in adoles-
cent males. Eur J Hum Genet. 2010 Dec;18(12):1339-43.
25. Viljakainen H, Andersson-Assarsson JC, Armenio M, Pekkinen M, Pettersson M, Valta H,
et al. Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in
Finland. PLoS One. 2015;10(7):e0131883.
26. Greenhill C. Obesity. Copy number variants in AMY1 connected with obesity via carbohy-
drate metabolism. Nat Rev Endocrinol. 2014 Jun;10(6):312.
27. Falchi M, El-Sayed Moustafa JS, Takousis P, Pesce F, Bonnefond A, Andersson-Assarsson
JC, et al. Low copy number of the salivary amylase gene predisposes to obesity. Nat Genet. 2014
May;46(5):492-7.
28. Mejia-Benitez MA, Bonnefond A, Yengo L, Huyvaert M, Dechaume A, Peralta-Romero J, et
al. Beneficial effect of a high number of copies of salivary amylase AMY1 gene on obesity risk in
Mexican children. Diabetologia. 2015 Feb;58(2):290-4.
29. Astrup A, Raben A, Geiker N. The role of higher protein diets in weight control and obesity-
related comorbidities. Int J Obes (Lond). 2015 May;39(5):721-6.
30. Kral TV, Whiteford LM, Heo M, Faith MS. Effects of eating breakfast compared with skip-
ping breakfast on ratings of appetite and intake at subsequent meals in 8- to 10-y-old children.
Am J Clin Nutr. 2011 Feb;93(2):284-91.
31. Reinehr T, Wolters B, Roth CL, Hinney A. FTO gene: association to weight regain after
lifestyle intervention in overweight children. Horm Res Paediatr. 2014;81(6):391-6.
32. Lourenco BH, Qi L, Willett WC, Cardoso MA. FTO genotype, vitamin D status, and
weight gain during childhood. Diabetes. 2014 Feb;63(2):808-14.
33. Newby PK. Plant foods and plant-based diets: protective against childhood obesity? Am J
Clin Nutr. 2009 May;89(5):1572S-87S.
34.https://www3appliedbiosystemscom/cms/groups/global_marketing_group/documents/gen-
eraldocuments/cms_098456pdf.
9



26-28 2016


www.pediatric-subspec.gr


(International Pediatric Association IPA)

IPA


&
-
-
& - ()
- -
- -
-
& -
- -
- -
-
-
-
-
- 10
-
-

/
EVEREST TRAVEL & CONGRESSES
15, 15451 . 14 - 16, 105 52
T: 2107771140 : 2103249242
F: 2107771663 F: 2103242395
W: www.e-child.gr W: www.everesttravel.gr
E: grammateia@e-child.gr E: conference@everesttravel.gr

176

: sexualization 24, ,
11527
./F. 210-7710824
e-mail: info@youth-health.
. , . gr


: .
,

, .


.

. ,
,
. ,
.
, , .

,
. , , ,
, .

.
,
.
: ,
,

.

: , , , -
,

.
.

(..)
/ ,
. &
.
REVIEW ARTICLES

177

Correspondence
Artemis Tsitsika
Sexualization of children and adoles-
24 Mesogeion Av, Athens,
11527
e-mail: info@youth-health.
cents
gr
T./F. +302107710824 A. Tsitsika, V. Dimitrakopoulou

Abstract
Background: Sexualization is a relatively new issue. he observation of the phenomenon and its
impact on children and adolescents seem to interest the contemporary literature, constituting a
modern age danger to individual sexual development, for both girls and boys. Part of the youth
sexualization process is the repeated exposure to gender stereotypical ideas and images, which
contributes to sexist attitudes and beliefs, as well as stereotyped perceptions of behavior towards
men and women. Psychological researchers report that girls learn to think of and treat their own
bodies as objects of others desires. Sexist attitudes and behaviors are well commercialized by the
market and repetitively performed in popular culture. Girls are major consumers of media and
receive and engage with these messages every day. According to bibliography, sexualization is a
phenomenon present in most European countries. It occurs across cultures and social classes,
although the channels may vary. Review evidence suggest that sexualization links to a variety of
negative and harmful consequences which affect youths optimal emotional, psychosocial and
sexual development. Current culture, parents, schools, and peers also sometimes contribute to
the sexualization of girls. Research in Europe is limited and deficient in terms of intervention ap-
proaches towards the phenomenon. Adolescents should gain knowledge and life-coaching skills
on areas that are not easy to deal with, such as self respect and filtering media and internet in-
formation.
Conclusions: Gaining more knowledge about sexualization and defining the phenomenon and
its consequences to youth, would firstly facilitate the identification of the young victims, leading
to efficient intervention approaches.

Keywords: sexualization, sexual objectification, adolescence, child abuse, sexism




, .
1980,
. ,
,

.


A. Tsitsika
V. Dimitrakopoulou
,
Adolescent Health Unit . H
(..U.), Second Depart-
ment of Pediatrics, . ,
P. & A. Kyriakou Chil- ,
drens Hospital, University
of Athens, Greece (1,2). -


(3,4). ,
: sexualization

178

, ,
.
, - ,

(5).

(.. ) ,
. ,

(2).

(6). ,
. KaiserFamilyFoundation (2003),
, 68% ,
, /
, , , chat-
rooms, (7-10).
Roberts (2005) , 47% 8-18
5
(8).
, ,
,
(11,12),
, (13)
(14,15).
,
(16).


(17). ,
, , ,
.
, ,

, (18).
, .
,
. ,
hip-hop ,
(2). ,
,
, (19-22).
,

,
(23).


(sexualiza-
tion) , .

(23),

,
(24). ,
179

,
, , (25-27),
, ,
(28,29),
.


. Beasley Standley (2002) 64
.
( 14% ).
, ,

(30). Dill, Gentile and Richter (2005) , 20
1999,
(31). Ward Rivadeneyra (2002)
84%

(32). 40
, , 38
(1.5%) (
). ,
85% ,
,
(33).


. Liss (2011)
(eight-item
Enjoyment of Sexualization Scale, ESS)
,

.
(34).
-
, ( 1).

. ,

,
(2). , ,


.

, , ,

(2).

. 77.000
18 2005, 15% 2000,
(35).


,
: sexualization

180

, ,
.
, (36). ,
,
(37,38).
(39).
-
,
(2).

H ,
,
grooming (10). -
,
online (40).
, .

.

.

(41).
.

(2). 18
, (42).
H
, (2).
, (~10-12 years old) ,
,

, -
, (43).

1:

/
:

/

181

-
,
.
, ,
, .
,

(9,10). , , Ward (2015)
,
,
(44). , Near
(2013),
video game

, (45).

(46,47).

, , ,
(48-50)
(51). Tiggemann Slater
(2014)
(52).
, , , ,
,
- (2).
,
,
(53,54).
, . Thorne (1993)
(55),
Brown (2003) ,
, ,
(26).

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



. , A

(2) ( 2).

.
,
(56).
,

.
: sexualization

182


,
, ,
, (2).
peer to
peer. , ,

.
:
, ,
,
,
(2,43)
( 2).



, (57-60). ,

.
,
, , ,
(2). Gerber (2008)

,
,
(61).
, .
.
, ,

. A (2010)
, , ,
,
,
,
, (2).
, ,

, ,

.


, ,


(2). ,
, (2).
1
, .
,
,
.
183

2:

- :
, ,
.

- :
,

- peer t peer

- ,

- , -

-

- /

- /

- ,

- ( ) peer
to peer
: sexualization

184

,
-,
,
.
(life coaching skills) ,

( 2).
, , ,
,

. ,

,
,
.


1. Task Force on the Sexualization of Girls ( 2007 ). Report of the APA Task Force on the
Sexualization of Girls. Washington, DC: American Psychological Association. Available at www.
apa.org/pi/wpo/sexualization.html
2. American Psychological Association, Report of the American Psychological Association Task
Force on the Sexualisation of Girls (2010), Washington, DC, American Psychological Associa-
tion (APA). Available at http://www.apa.org/pi/women/programs/girls/report-full.pdf
3. Fredrickson, B.L., Roberts, T.A. (1997). Objectification theory:Toward understanding
womens lived experience and mental health risks. Psychology of Women Quarterly, 21;173-
206.
4. McKinley, N.M., Hyde, J.S. (1996).The Objectified Body Consciousness Scale. Psychology
of Women Quarterly, 20;181-215.
5. Strasburger, V.C. (2009). Children, adolescents and the media: what we know, what we
dont know and what we need to find out (quickly!).Arch Dis Child, 94(9);655-7.
6. Fine, M., McClelland,S.I. (2006). Sexuality Education and Desire: Still Missing after All
These Years.Harvard Educational Review, 76(3);297-338.
7. Kaiser Family Foundation. (2003). New study finds children age zero to six spend as much
time with TV, computers and video games as playing outside [Press release]. Available at www.
kff.org/entmedia/entmedia102803nr.cfm
8. Roberts, D., Foehr, U., Rideout, V. (2005). Generation M: Media in the lives of 8-18 year
olds. Menlo Park, CA: Kaiser Family Foundation.
9. Tsitsika, ., Critselis, ., Kormas, G., Konstantoulaki, E., Constantopoulos, A., Kafetzis,
D. (2009). Adolescent Pornographic Internet Site Use: A multivariate regression analysis of the
predictive factors of use and psychosocial implications. Cyberpsychology& Behavior, 12(5);545-
50.
10. Tsitsika, A., Janikian, M., Tzavela, E., Schoenmakers, T.M., lafsson, K., Halapi, E., et al.
(2013). Internet use and Internet addictive behaviour among European adolescents: A cross-
sectional study. National and Kapodistrian University of Athens (N.K.U.A.), Athens: EU NET
ADB. Available at www.eunetadb.eu
11. Andsager, J.L., Roe, K. (1999). Country music video in countrys year of the woman. Journal
of Communication, 49;69-82.
12. Seidman, S.A. (1992).An investigation of sex-role stereotyping in music videos. Journal of
Broadcasting & Electronic Media, 36;209-216.
13. Sommers-Flanagan, R., Sommers-Flanagan, J., Davis, B. (1993).Whats happening on music
television? A gender role content analysis. Sex Roles, 28;745-753.
14. Arnett, J.J. (2002).The sounds of sex: Sex in teens music and music videos. In Brown,J.
Walsh-Childers, K. SteeleJ. (Eds.), Sexual teens, sexual media (253-264). Hillsdale, NJ: Erl-
baum.
15. Gow, J. (1996). Reconsidering gender roles on MTV: Depictions in the most popular music
185

videos of the early 1990s. Communication Reports, 9;151-161.


16. McMahon, K. (1990).The Cosmopolitan ideology and the management of desire. Journal of
Sex Research, 27;381-396.
17. Duffy, M., Gotcher, J.M. (1996). Crucial advice on how to get the guy:The rhetorical vision
of power and seduction in the teen magazine YM. Journal of Communication Inquiry, 20;32-
48.
18. Liebau, C.P. (2007). Prude: How the sex obsessed culture damages girls. Boston, MA: Cent-
er Street Publishing.
19. Atlas, J.G., Smith, G.T., Hohlstein, L.A., McCarthy, D.M., Kroll, L. (2002). Similarities
and differences between Caucasian and African American women on eating disorder risk factors
and symptoms. International Journal of Eating Disorders, 32(3);326334.
20. Barry, D.T., Grilo, C.M. (2002). Eating and body image disturbances in adolescent psy-
chiatric inpatients: Gender and ethnicity patterns. International Journal of Eating Disorders,
32(3);335343.
21. Goodman, J.R. (2002). Flabless is fabulous: How Latina and Anglo women read and incor-
porate the excessively thin body ideal into everyday experience. Journalism and Mass Communi-
cation Quarterly, 79(3);712728.
22. Hesse-Biber, S., Leavy, P., Quinn, C.E., Zoino, J. (2006). The mass marketing of disordered
eating and eating disorders: The social psychology of women, thinness and culture. Womens
Studies International Forum, 29;208224.
23. Buckingham, D., Bragg, S. (2004). Young people, sex and the media: the facts of life? Lon-
don, UK: Pelgrave.
24. Thornburgh, D., Lin, H. (2002). Youth, Pornography and the Internet. Washington, DC:
National Academy Press.
25. Wolke, D., Woods, S., Stanford, K., Schulz, H. (2001). Bullying and victimization of pri-
mary school children in England and Germany: Prevalence and school factors. British Journal of
Psychology, 92(4);673696.
26. Brown, L.M. (2003). Girlfighting: Betrayal and rejection among girls. New York: New York
University Press.
27. Petersen, J.L, Hyde, J.S. (2009). A longitudinal investigation of peer sexual harassment vic-
timization in adolescence. J Adolesc, 32(5);1173-88.
28. Sidor, A., Baba, C.O., Marton-Vasarhelyi, E., Chereches, R.M. (2015). Gender differences
in the magnitude of the associations between eating disorders symptoms and depression and
anxiety symptoms. Results from a community sample of adolescents. J Ment Health, 19;1-5.
29. Vardar, E., Erzengin, M. (2011). The prevalence of eating disorders (EDs) and comorbid
psychiatric disorders in adolescents: a two-stage community-based study. Turk PsikiyatriDerg,
22(4);205-12.
30. Beasley, B., Standley,T.C. (2002). Shirts vs. skins: Clothing as an indicator of gender stereo-
typing in video games. Mass Communication and Society, 5;279-293.
31. Dill, K.E., Gentile, D.A., Richter, W.A., Dill, J.C. (2005).Violence, sex, race, and age in
popular video games:A content analysis. In Cole, E. Henderson-Daniel, J. (Eds.), Featuring
females: Feminist analyses of media (115-130).Washington, DC:American Psychological As-
sociation.
32. Ward, L.M., Rivadeneyra, R. (2002). Dancing, strutting, and bouncing in cars:The women
of music videos. Paper presented at the annual meeting of the American Psychological Associa-
tion, Chicago.
33. ODonohue, W., Gold, S.R., McKay, J.S. (1997). Children as sexual objects: Historical and
gender trends in magazines. Sexual Abuse: Journal of Research & Treatment, 9;291-301.
34. Liss, M., Erchull, M.J., Ramsey, L.R.(2011).Empowering or oppressing? Development and
exploration of the Enjoyment of Sexualization Scale.PersSocPsychol Bull, 37(1);55-68.
35. American Society of Plastic Surgeons. (2006a). 2005 cosmetic surgery age distributions 18 or
younger.Available at www.plasticsurgery.org/public_education/ loader.cfm?url=/commonspot/
security/ getfile.cfm&PageID=17849
36. Slater, A., Tiggemann, M. (2002).A test of objectification theory in adolescent girls. Sex
Roles, 46;343-349.
: sexualization

186

37. Groesz, L.M., Levine, M.P., Murnen, S.K. (2002).The effect of experimental presentation of
thin media images on body satisfaction:A meta-analytic review. International Journal of Eating
Disorders, 31;1-16.
38. Holmstrom, A.J. (2004).The effects of the media on body image:A meta-analysis.Journal of
Broadcasting & Electronic Media, 48;196-217.
39. Stice, E., Shaw, H. (2003). Prospective relations of body image, eating, and affective dis-
turbances to smoking onset in adolescent girls: How Virginia slims. Journal of Consulting and
Clinical Psychology, 71;129-135.
40. Mitchell, K.J., Jones, L.M., Finkelhor, D., Wolak, J. (2011). Internet-facilitated commercial
sexual exploitation of children: Findings from a nationally representative sample of law enforce-
ment agencies in the U.S. Sexual Abuse: A Journal of Research and Treatment, 23(1);43-71.
41. Lindberg, S.M., Grabe, S., Hyde, J.S. (2007). Gender, pubertal development and peer sexual
harassment predict objectified body consciousness in early adolescents. Journal of Research on
Adolescence, 17;723742.
42. Boyer, D., Chapman, L., Marshall, B.K. (1993). Survival sex in King County: Helping wom-
en out [Report to the King County Womens Advisory Board]. Seattle,WA: Northwest Resource
Associates.
43. , ., , ., , ., , ., ,
., , ., et al (2010). :
. , 73:206-212.
44. Ward, L,.M., Vandenbosch, L., Eggermont, S. (2015). The impact of mens magazines on
adolescent boys objectification and courtship beliefs.J Adolesc, 39;49-58.
45. Near, C.E. (2013). Selling Gender: Associations of Box Art Representation of Female Char-
acters With Sales for Teen- and Mature-rated Video Games. Sex Roles,1;68(3-4);252-269.
46. Bandura,A. (1986). Social foundations of thought and action:A social cognitive theory. En-
glewood Cliffs, NJ: Prentice-Hall.
47. Bandura,A. (1994). Social cognitive theory of mass communication. In Bryant, J.,Zillman,
D. (Eds.), Media effects:Advances in theory and research (61-90). Hillsdale, NJ: Erlbaum.
48. Bussey, K., Bandura,A. (1984). Influence of gender constancy and social power on sex-linked
modeling. Journal of Personality and Social Psychology, 47;1292-1302.
49. Bussey, K., Bandura,A. (1992). Self-regulatory mechanisms governing gender development.
Child Development, 63;1236-1250.
50. Lips, H. (1989). Gender role socialization: Lessons in femininity. In Freeman, J. (Ed.),
Women:A feminist perspective (197-216). Mountain View, CA: Mayfield.
51. Huston, A.C., Wright, J.C. (1998). Mass media and childrens development. In Damon,
W., Sigel,I.E.,Renninger, K.A. (Eds.), Handbook of child psychology (Vol 4). Child psychology
in practice (999-1058). New York:Wiley.
52. Tiggemann, M, Slater, A. (2014). Contemporary girlhood: maternal reports on sexualized
behavior and appearance concern in 4-10 year-old girls.Body Image, 11(4);396-403.
53. Levine, M.P., Smolak, L., Hayden, H. (1994).The relation of sociocultural factors to eating
attitudes and behaviors among middle school girls. Journal of Early Adolescence, 14;471-490.
54. Nichter, M. (2000). Fat talk:What girls and their parents say about dieting. Cambridge, MA:
Harvard University Press.
55. Thorne, B. (1993). Gender play: Girls and boys in school. New Brunswick, NJ: Rutgers
University Press.
56. Potter,W.J. (2004).Argument for the need for a cognitive theory of media literacy. American
Behavioral Scientist, 48;266-272.
57. Abernathy, T.J., Webster, G., Vermeulen, M. (2002). Relationship between poverty and
health among adolescents. Adolescence, 37;55-67.
58. Bonhauser, M., Fernandez, G., Pschel, K.,Yaez, F., Montero, J., Thompson, B., et al
(2005). Improving physical fitness and emotional well-being in adolescents of low socioeconom-
ic status in Chile: Results of a school-based controlled trial. Health Promotion International,
20;113-122.
59. Crews, D., Lochbaum, M.R., Landers, D.M. (2004). Aerobic physical activity effects on
psychological well-being in low-income Hispanic children. Perceptual and Motor Skills, 98;319-
187

324.
60. McAuley, E. (1994). Physical activity and psychosocial outcomes. In Bouchard, C.,
Shephard,R.J., Stephens, T. (Eds.), Physical activity, fitness and health (551-568). Champaign,
IL: Human Kinetics Publishers.
61. Gerber, J. (2008).Treatment of sexually compulsive adolescents. PsychiatrClin North
Am,31(4);657-69.

188

A
N.
8, .
15232
. ,
e-mail: mariza.vass@gmail.
com
. 6944794442

(AA)
.
4-12 . 10-
20%. . ,
.
.
,
, ,
. : )
, )
(, ,
, , ,
, ).
, ,
,
, .

,
. -
.

: , , ,
.

.
-
,


-




. &
.
REVIEW ARTICLES

189

Correspondence
Maria N. Vasilopoulou
Growing pains
8 Ippokratous str, Penteli,
15232
Maria N. Vasilopoulou, Maria Tsolia
e-mail: mariza.vass@gmail.
com
. +306944794442
Abstract
Growing pains (GP) is the most common musculoskeletal complaint in childhood. The term
refers to recurrent lower limb pain, affecting children aged 4-12 years of age. Its frequency in
schoolchildren is estimated about 10-20%. It is a benign clinical entity. The diagnosis of GP
can be made clinically, based on history and physical examination, by exclusion of more serious
pathologic conditions.
This review article presents data concerning the epidemiology, the etiology/pathogenesis, the
clinical characteristics, the differential diagnosis and the treatment of GP. It also reports all the
available publications that studied: a) GPs prevalence in different age groups of the general
childrens population, b) the association between GPs pathogenesis and several factors (growth,
pain threshold, genetics, mild anatomic abnormalities, psychological distur- bance, restless legs
syndrome, local overuse). Although many of these theories have not been sufficiently investigat-
ed, the lower pain threshold in children with GP, the absence of any evidence of inflammation,
along with the familial nature of the disorder, classify GP in the group off unctional pain syn-
dromes. These syndromes occur spontaneously or are easily provoked and they are characterized
by genetic susceptibility, absence of any or mild somatic pathology and comorbid inter-relation-
ships with other idiopathic pain syndromes. They are attributed to disordered somatosensory
processing and they are influenced by psychological factors.

Keywords: Childhood, lower limb pains, growing pains, musculoskeletal pain syndromes.



. (), ,

,
.
, Peterson, ,
,
, .
.
,
( 1) (1).
(Diagnostic and Statistical Man-
ual for Primary Care / DSM-PC Child and Adolescent Versions) (2),
Maria N. Vasilopoulou
Dr, Pediatrician-Inten- (somatic complaint variation). ,
sivist, PICU Pentelis
Children Hospital
(3).
Maria Tsolia
Professor, 2nd Depart-
AA (growing pains) 1823(4).
ment of Pediatrics, School ,
of Medicine, National and . ,
Kapodistrian University of
Athens, Greece (5).

190

1: Petersn (1)

1. . .

2. .

3. , , .

4. O .

5. .

6. .

7. .


AA 4-37%. (6-10). 2,
70
/ - .
,
, -
. :
- ,
- ( /
, / /).
, ,
10% 20% (1, 11-13)
(7-9, 14).


.
,
(non inflammatory pain syndromes).
O 60 :

1.
1950
(, , , ) (8, 18).
,
(19), ,
(18). (18)
180 4-6 ,
. (20).
130 (21).
/
(hyper mobility syndrome) (22, 23). To
.

.
(24, 25).
2: 191
-
()

1. Hawksley(6) 1939 . 4-14 505 33,6%

2. Naish and 1951 . ( 4-15 721 1. 4,2%


Apley(7) )
2.
3
3.
.

3. Brenning(8) 1960 ( 6-7 257 13,6%


)
10-11 419 19,8%

4. Cullen and 1963 A 4-15 3.440 4,5%


MacDonald

5. Oster and 1972 ( 6-19 2.178 15,5%


Nielsen (9),(11) )

6. Abu-Arafeh and 1996 . ( 5-15 2.165 1. >2 /, 2,6%


Russell(14) )


.
2.
3.
/

.
4.
<72 .
5.


.
6.

( )

7. Mikkels- 1997 ( 9- 13 1.626 1. 11,7%


sonet al. (13) ) .
2.
1 /
3.
3.
.

8. Oberklai- 1997 8-9 1.605 , 11,5%


detal.(14)

9. Evans A.(10) 2004 ( 4-6 1.445 1. 36,9%


)
Peterson.
2.
/.

10. VanDijk. 2006 ( 9-13 495 21%


etal.(16) )

11. Golding J, 2012 . 5 9.380 1. . 4,17%


Northstone K 2013 8 7.872 2. 21,4%
(Avon Longitu- () 13 6.502 . 15%
dinal study 13.988 3.
of Parents and
Children (17) .

Peterson.

192

2.
,
167
25 . 90% -
.
(26),


.

(27).

3.
E
(28, 29).
(dolorimeter) Fischer.

.
. ,
(29) 5
,


.

,
(Pain mplification Syndrome).
(30), 33
29 -
(,
, , , ). ,

.
- .

4.

(17,21,31)
( - overusesyndrome).
/
, .
(31) 39
/, (32).
,

.
.
20 20 ,
(33).

.
.
,

.
193

(34) ( ,
)
.

5. (restless legs syndrome - RLS)


- , -
, ,
,
, .

(35).
(36).
RLS .
: 1.
(, )
. 2. -
. A 2/3 RLS
/ (37).

(37).

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

RLS :
) 4
) .

) 4
) 2-3

RLS.
1. .
2. RLS /.
3. >5 / (Periodic Leg Movements
in Sleep - PLMS ) .
:

.
,
RLS (38-40).
, RLS .
,
RLS ,
.
. (41)

194

6.
1960 (8). , Evans
70% (42).

,
,
(41, 43, 44).

7.
, ,
2-5 , (45).
: )
. . )
. ,
, ,
.

8.
(,
) (7, 9, 46).
, , ,
,
,
(15).
.
, , - 45%
-
(47). ,
,

(14).
.
, 622 , 6-18
, (, , , ),
2-3
, ,
(48).

9.
(47),
,

.
(49).


(, ,
) ,
, ,
, Mayer
Bushnell (50).

,
,
-
195

. (51). ,

.


,
. , - (1,7,9,11,52,53):
O .
, .
, ,
, .
( ).
, . ,
,
.
, .
. ,
. .
.

.
(54).
. /
, (42, 43, 47, 48).
, ,
(, ).



( 3). , :


, .
.
,
(55). 20-40% (56).
, ,

,
.

/
/ ,
. , ( Brodie,
) .
,
.


,
. ,
. ,
(57). Ewing ,
(58).

196

3:


wing

O


(.. )

()

(Patel-

lofemoralpainsyndrome)

.Gaucher

Leg Pain. In: Tunnessen WW, Roberts KB. Signs and Symptoms in Pediatrics, 3rd edition, Lippincott, Williams, and Wilkins,
Philadelphia, 1999.p.633Atar D, Lehman WB, Grant AD. Growingpains.OrthopRev 1991; 20:133


/ ,
.


, , , .



.
.
, ,
.
.
10-15 (59).


Legg-Calv-Perthes
3-12
197

( 5-7 ). 10-20%
(60). , 10%
. ,
.
.
,
(61).


, ,
.



Chlamydia pneumoniae, (, , ,
, , . coli,). -
. 20-90%
(, /
, , ) (62).



.
,

(63). 1-2%
1985 Yunis Masi
(64) ( 4).
( ,

),
.
, ,
, , ,
.

.
, ( ,
, C- ), :
- ( , , -
, ).
- , , .
- .
- .
- ( ,
, , , ).
- (52,53).

. (,
, , ) .
(19).
,
.

198

4:

1. 3
.

2. (..,).

3. .

4. .

1.

2.

3.

4.

5.

6.

7.

8. .

9. .

10. / .
: 4 3 10 .


1. Peterson H. Growing pains, PediatrClin North Am 1986 ;33:1365-1372.
2. Wolraic ML, Felice ME, Drotar D. The classification of child and adolescent mental diagnosis
in primary care. In: Diagnostic and Statistical Manual for Primary Care/DSM-PC Child and
Adolescent Versions. Elk Grove Village, IL: American Academy of Pediatrics 1996.
3. Silber JT. Somatization Disorders: Diagnosis,Treatment and Prognosis. Pediatr
Rev2011;32:56-64.
4. Duchamp M. Maladies de la croissance. In: Memoires de Medecine Practique,
Levrault FG(Ed), Jean Frederic Lobstein,Paris,1823.
5. Editorial: Growing pains.Br Med J 1972; 3:365.
6. Hawksley JC. Race, rheumatism, and growing pains. Arch DisChild 1931;6:303
7. Naish JM, Apley J. Growing pain:a clinical study of non-arthritic limb pains in children.
Arch Dis Child 1951;26:134.
8. Brenning R. Growing pains. ActaSoc Med Upsala 1960;65:185.
9. Oster J. Reccurent abdominal pain, headache and limb pains in children and adolescents.
Pediatrics1972;50:429.
10. Evans AM, Scutter SD. Prevalence of growing painsin young children. J Pediatr 2004;145
:255.
199

11. Oster J, Nielsen A. Growing pains. A clinical investigation of a school


population. Acta PaediatrScand 1972;61:329.
12. Brady M, Grey M. Growing pains: a myth or a reality. J Pediatr Health Care1989;3: 219
13. Mikkelsson M, Salminen JJ, Kautiainen H. Non-specific musculoskeletal pain in preadoles-
cents. Prevalence and 1-year persistence. Pain 1997;73:29-35
14. Abu-ArafehI, Russell G. Recurrent limb pain in school children. Arch Dis Child 1996;74:336
15. Oberklaid F, Amos D, Liu C, Jarman F, Sanson A, Prior M. Growing pains : clinical and
behavioral correlates in a community sample. J Dev Behav Pediatr 1997;18:102-6.
16. Van Dijk A, McGrath PA, Pickett W, VanDen Kerkhof EG. Pain prevalence in nine- to
13-year-old school children. Pain Res Manage 2006;11:234-240.
17. Bishop L J, Northstone K, Emmett MP, Golding J. Parental accounts of the prevalence,
causes and treatments of limb pain in children aged 5 to 13 years: a longitudinal cohort study.
Arch Dis Child 2012;97:52-53.
18. Evans AM. Relationship between growing pains and foot posture in children: single-case
experimental designs in clinical practice. J Am Podiatr Med Assoc 2003;93:111-117.
19. Baxter MP and Dulberg C. Growing pains in childhood. A proposal for treatment. J Pedia-
trOrthop 1988;8:402.
20. Evans AM, Scutter SD. Are foot posture and functional health different in children with
growing pains? PediatrInt 2007;49:991-6.
21. Kaspiris A, Zafiropoulou C. Growing pains in children: Epidemiological
analysis in a Mediterranean population. Joint Bone Spine. 2009;76:486-90.
22. Annan JD, Abu-Rajab RB, Young D, Bennet G C. Growing pains in children are associated
with joint hypermobility. J Bone Joint Surg Br 2010 vol.92-Bno.SUPP III 372
23. Viswanathan V, Khubchandani R P. Joint hypermobility and growing pains in school chil-
dren. Clinical & Experimental Rheumatology, 2008; 26.5: 962.
24. Mikkelsson M, Salminen JJ, Kautiainen H. Joint hypermobility is not a contributing factor
to musculoskeletal pain in pre-adolescents. JRheumatol. 1996 ; 23:1963-7
25. Leone V, Tornese G, Zerial M, Locatelli, C, Ciambra, R, Bensa, M, et al. Joint hypermobil-
ity and its relationship to musculoskeletal pain in schoolchildren: a cross-sectional study. Arch.
Dis. Child. 2009;94:8 627-632.
26. Lampl M. In: Lampl M, ed. Saltation and Stasis in Human Growth and Development: Evi-
dence, Methods and Theory. London: Smith Gordon,1999.
27. Noonan KJ, Farnum CE, Leiferman EM, Lampl M, Markel MD, Wilsman NJ. Growing
pains: Are they due to increased growth during recumbency as documented in a lamb model? J
Pediatr Orthop 2004; 24:726-731.
28. Hashkes PJ, Friedland O, Jaber L, Cohen HA, Wolach B, Uziel Y. Decreased pain threshold
in children with growing pains. J Rheumatol 2004;31:610-3.
29. Uziel Y, Chapnick G, JaberL,Nemet Dan, Hashkes PJ. Five-year outcome of children with
growing pains: correlations with pain threshold. The Journal of Pediatrics 2010;156: 838-840.
30. Pathirama S, Champion D, Jaaniste T, YeeA, Chapman C. Somatosensory test responses in
children with growing pains. Journal of Pain Research 2011;4:393-400.
31. Friedland O, Hashkes PJ, Jaber L, Cohen H. A., Eliakim A., Wolach B., et al. Decreased
bone speed of sound in children with growing pains measured by quantitative ultrasound. J
Rheumatol 2005;32:1354-1357.
32. Foldes AJ, Rimon A, Keiman DD, Popovetzer MM. Quantitative ultrasound of the tibia:a
novel approach for assessment of bone status. Bone 1995;17: 363-7.
33. ., ., ., ., .
. () 28
, ,.102.
34. Lowe MR, Hashkes PJ. Growing pains: a noninflammatory pain syndrome of early child-
hood. Nature Clinical Practice Rheumatology 2008 ;4:542-549.
35. The International Classification of Sleep Disorders, 2ndedn.2005. American Academy of
Sleep Medicine. Westchester.
36. Kotagal S, Silber MH. Childhood onset restless legs syndrome. Am Neurol 2004;56:803-7
37. Picchietti D, Allen RP, Walters AS., Davidson JE, Myers A, Ferini-Strambi L. Restless legs

200

syndrome: prevalence and impact in children and adolescents- the Peds REST study (see com-
ment).Pediatrics 2007;120:253-266.
38. Walters AS. Is there a subpopulation of children with growing pains who really have restless
legs syndrome? A review of the literature. Sleep Med 2002;3: 93-8
39. Rajaram SS, Walters AS, England SJ, Mehta D and Nizam F. Some children with growing
pains may actually have restless legs syndrome.Sleep2004;27: 767-773.
40. Wong M W, Williamson B D, Qiu, W, Champion D, & Teng A. Growing pains and peri-
odic limb movements of sleep in children. Journal of paediatrics and child health, 2014;50:455-
460.
41. Champion D, Flynn C, Taylor A, Jaaniste T. Growing pains shares genetic determinants
with the restless legs syndrome. Twin Research and Human Genetics 2010; 13:250.39.
42. Evans AM, Scutter SD, Lang MG, Dansie BR. Growing pains in young children: a study
of the profile, experiences and quality of life issues for four to six year old children with reccurent
leg pain. The Foot 2006;16:120-124.
43. Wong MW. Growing pains and its associations with restless legs syndrome and other func-
tional pain syndromes: A twin family case-control study.FAC 4503 Independent Learning
Project .arch 2011, University of New South Wales, Sidney, Australia.
44. Champion D, Pathirama S, Flynn C, Taylor A, Hopper JL, Berkovic SF, Jaaniste T ,Qiu W.
Growing pains: twin family studyevidence for genetic susceptibility and a genetic relationship
with restless legs syndrome. Eur J Pain 2012;16:1224-31.
45. Makay B. Is there a role of melatonin in the development of growing pains? Medical Hypoth-
eses2009;72:225
46. Sherry DD. An overview of amplified musculoskeletal pain syndromes. J Rheumatol Sup-
pl2000;58:44-48
47. Aromaa M, Sillanpaa M, Rautava P, Helenius H. Pain experience of children with head-
ache and their families: A controlled study. Pediatrics 2000;106:270-275.
48. Roth-Isiqkeit A, Thyen U, Stoven H, Schwarzenberger J, Schmucker P. Pain among children
and adolescents: restrictions in daily living and triggering factors. Pediatrics 2005;115:152-62.
49. Hashkes PJ, Gorenberg M, Oren V, Friedland O and Uziel Y. Growing pains in children
are not associated with changes in vascular perfusion patterns in painful regions. Clin Rheumatol
2005;24:342-345.
50. Mayer EA, Bushnell MC. Functional Pain Disorders: Time for a Paradigm Shift? In E.A.
Mayer & M.C. Bushnell (Eds.), Functional Pain Syndromes: Presentation and Pathophysiology
(pp.431-565). Seattle: IASP Press.2009
51. Diatchenko L, Nackley AG, Slade GD, Fillingim R, Maixner W. Idiopathic paindisorders-
pathways of vulnerability. Pain 2006;123:226-230.
52. Halliwell P, Monsell F.Growing pains: a diagnosis of exclusion. Practitioner 2001;245:620.
53. Pavone V, Lionetti E, Gargano V, Evola F, Costarella L, Sessa G. Growing Pains: A study of
30 cases and a review of literature. J Pediatr Orthop. 2011; 31:606-9.
54. Macarthur C, Wright JG, Srivastava R, Rosser W. Variability in physicians reported or-
dering and perceived reassurance value of diagnostic tests in children with growing pains. Arch
Pediatr Adolesc Med 1996;150:1072.
55. Kocher MS, Bishop JA, Weed B, Hresko MT, Millis MB, Kim YJ, Kasser JR Delay in diag-
nosis of slipped capital femoral epiphysis. Pediatrics. 2004;113(4):e322
56. Hgglund G, Hansson LI, Ordeberg G, Sandstrm S. ilaterality in slipped upper femoral
epiphysis. J Bone Joint Surg Br. 1988;70(2):179
57. Springfield DS, Gebhardt MC. Bone and soft tissue tumors. In: Lovell and Winters Pedi-
atric Orthopaedics, 6th, Morrissy RT, Weinstein SL (Eds), Lippincott Williams & Wilkins,
Philadelphia 2006. p.493.
58. Widhe B, Widhe T. Initial symptoms and clinical features in osteosarcoma and Ewing sar-
coma. J Bone Joint Surg Am. 2000;82: 667
59. Coady CM, Micheli L J. Stress fractures in the pediatric athlete. Clin Sports Med. 1997;16
(2):22
60. Wenger DR, Ward WT, Herring JA. Legg-Calv-Perthes disease. J Bone Joint Surg Am.
1991;73(5):778.
201

61. Uno A, Hattori T, Noritake K, Suda H. Legg-Calv-Perthes disease in the evolutionary


period: comparison of magnetic resonance imaging with bone scintigraphy. J Pediatr Orthop.
1995;15(3):362.
62. Leirisalo-Repo M. Reactive arthritis. Scand J Rheumatol 2005 ;34:251.
63. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain
2011;152:S2
64. Yunis MB, Masi AT. Juvenile primary fibromyalgia syndrome. A clinical study of thirty-
three patients and matched normal controls. Arthritis Rheum 1985; 28:138.

202

: A

,
11527,
e-mail: psonistavroula@

gmail.com
. / F. 2107795553




.
, ,
,
, . >80
>20 ,
,
.
.

.
, , , ,
. Next Generation Sequenc-
ing (NGS)
.

.

: , , ,
,






,

,
REVIEW ARTICLES

203

Correspondence
Stavroula Psoni
Ciliopathies: The central role of pri-
Thivon and Levadias St.,
11527, Athens
e-mail:psonistavroula@
mary cilia in a wide disease spectrum
gmail.com
T. / F. +302107795553 Stavroula Psoni, Helena Fryssira

Abstract
The ciliopathies comprise a heterogeneous group of disorders which are associated with muta-
tions at genes coding for proteins for the formation or functionality of the primary or immotile
cilia. Since these cilia are components of practically all cells, the ciliopathies present mainly with
retinal degeneration, renal disease and brain anomalies and secondarily with hepatic fibrocystic
disease, diabetes mellitus, obesity and skeletal dysplasias. More than 80 genes correspond to
more than 20 distinct disorders, while many diseases sharing some of the above features may be
classified as ciliopathies in the near future, when the cilia molecular mechanisms will be further
clarified. The cilia mainly induce cell signals and thus facilitate the cellular paracrine activity.
They also play major role in cell division and orientation through the participation in several
developmental pathways. The study of ciliopathies aids the comprehension of the mechanisms
of tumorigenesis, cysteogenesis, mental retardation and diabetes mellitus. The new diagnostic
technologies such as Next Generation Sequencing have optimized the genetic research through
the simultaneous study of several ciliopathetic genes. The dynamic development of Medical
Genetics in this field provides a powerful tool in genetic diagnosis, counseling and management
of the patients and their families.

Keywords: immotile cilia, retinal degeneration, renal disease, CNS malformations, heterogeneity


(primarycilium)

,
(ciliopathies) (1).
,

, (2). -
: , ,
, (2).
1000
40 (2).
: .
9+0
. ( 9+2)
(3).
Stavroula Psoni ATP
Helena Fryssira
Medical Genetics National (4). ,
and Kapodistrian Univer- (, )
sity of Athens, School of
(2).
Medicine, Aghia Sophia
Childrens Hospital,
(primary ciliary dyskinesia, PCD)
Athens -
- ,
(situsinversus) (5).
, ,

204


(6) ( 1). ,
,
. ,
: 1. ,
2. , 3. , 4.
5. (2).


, , , ,

(7). ,
. ,

,
(2).

-
,
, .

(ciliary assembly and disassembly):



, G1 G0 (8). ,

. ,
Golgi
( ),
(9,10)
( 1).
(9).
,
1:
.
.
(9,11).
(In-

traflagellar Transport, IFT) .
( IFT)
(12).

.
, S
intraflagellar trans-
(Microtubule-Organizing-Center, MTOC) (13). port
.

(9,13). ,
(steadystate) IFT
(assembly/disassembly).
IFT (kinesins-IImotors)
,
IFT-A, IFT IFT-B (2,14). (Zaghloul N, Genesis
, 2011;49:231-246)
205


.
NGS: Next Generation
Sequencing :
PCD: Primary Ciliary
Dyskinesia
IFT: Intraflagellar (15).
Transport ,
MTOC: Microtubule- .
Organizing-Center ,
PCP: PlanarCellPolarity Wnt
Shh: Sonic-Hedgehog Hedgehog, Notch, JAK-STAT, mTOR PDGF ( 2). O
Smo: Smoothened ( NEK8, PC1),
PTCH1: Patched ,
Homologue 1 (7,12).
mTOR: mammalian- ,
Target of Rapamycin :
PC1: polycystin-1
BBS: Bardet-Biedl 1. Wnt - Planar Cell Polarity (Non-Canonical Wnt-PCP):
Syndrome H (Planar Cell Polarity, PCP)
ADPKD: Autosomal
Dominant Polycystic (16,22). PCP
Kidney Disease ,
ARPKD: Autosomal .
Recessive Polycystic
Kidney Disease (9). ,
PC2: polycystin-2
ESRD: End-Stage Renal ,
Disease (22).
PKHD 1: Polycystic
Kidney and Hepatic 2. Wnt (Canonical Wnt pathway):
Disease 1 H Wnt 19
PCLD: Polycystic Liver ,
Disease - Disheveled (2,22).
vHL: von Hippel-
Lindau (NPHS2) Bardet-Biedl (Some) (16)
TSC: Tuberous Sclerosis ( 2). BBS
NPH: nephronophthisis -,
MCKD: Medullary . , Wnt
Cystic Kidney Disease - ,
JS: Joubert Syndrome (2,23). BBS canonical non-canonical
MTS: MolarTooth Sign Wnt , (2).
JSRD: Joubert Syn-
drome Related Disor- 3. Sonic-Hedgehog (Shh)
ders Shh
OFD: Orofaciodigital
Syndrome (PTCH1, Patched Homologue 1) (17). PTCH1 ,
MGS: Meckel-Gruber Smoothened (Smo), PTCH1
Syndrome Shh , Smo
JATD: Jeune Asphyxiat- IFT Shh (2,24).
ing Thoracic Dystrophy Shh
EVC: Ellis-van Creveld Gli (Gli1, Gli2, Gli3)(17) ( 2).
Syndrome
SRPS: Short-Rib Poly- 4. mTOR
dactyly Syndrome mTOR

206

(mammalian Target of Rapamycin)


(20).
PC1 (polycystin 1),
(DPKD), mTOR
tuberin (25).


,
.
,
,
, (2). -
,

, - ( 3).
(situsinversus),
,
, , ,
, ,
, (8).
,
, , (9).

. Bardet-Biedl (BBS)
,
(26,27). -
,

(28).
,
2:
,
.
(28,29).
lumping splitting ( 4).



. .

1. -- -
MKS1
.
( 1). (Autosomal Dominant MeckelGruber.
Polycystic Kidney Disease, ADPKD Autosomal Recessive Polycystic Kidney Disease, AR-
PKD) , .
(1).


(30). 1
ADPKD 1/400- 2 (PC1 and PC2).
1000, 12.5 (31).
Hedgehog
,
inutero. Hh (hedgehog)
, . Patched
, ,

, . 60 , 50%
(30).
, , -.
207

( 75% 60 ),
CED: Cranioectodermal ,
Dysplasia ( 8%) (32-34).
DDR: DNA Damage
Response 1: - - -

. Potter, . , PKHD1 Polyductin/


(6p12.3- fibrocystin
-, , p12.2)
(ARPKD) (
), /

. , PKD1 Polycystin-1
, / , (16p13.3) Polycystin-2
(ADPKD) PKD2
, , (4q22.1)

. (>20), PRKCSH Hepatocystin


, , , (19p13.2) SEC63
(PCLD) , SEC (6q21)

Von-Hippel Lindau / VHL (3p25.3) pVHL


(VHL) , , +
clear cell Ca , ,
,

O (C) , , , TSC1 Hamartin


, (9q34.13) Tuberin
, TSC2
(16p13.3)
Wnt


,
(80-85%) PKD1
16p13, 15-20% PKD2 4q21
(NPHP2) (31). polycystin-1 (PC1) polycystin-2 (PC2)
. Bardet-
Biedl. O BBS

, Ca++
stress (35).
PKD2 (PC2)
canonical (36).
non-canonical

ARPKD 1:20000
-. (End-Stage Renal Disease, ESRD) , ,
, ,
PKHD1 (Polycystic Kidney and Hepatic Disease-1)
.
-
6p12.3-p12.2 polyductin fibrocystin (37).
BBS4, ,
( )
CEP290 , (38). polyductin
OFD1

.
, ,
PC2(39).

,

ARPKD,
(38). PKHD1
(NPHP1,3,4,5 10). Caroli (40). ,

208

PRKCSH SEC
ADPKD , (PCLD,
Polycystic Liver Disease) (41).
, neoplasia in-
disguise
, ,

(40).
( , ane-
uploidy paradox),
,
(40).

, von Hippel-Lindau (vHL
(Tuberous Sclerosis, TSC) (40). H vHL

VHL ,
, (clearcell)
.
(42).
TSC 1:6000
TSC1 TSC2 .
(90%), ,
. TSC , ,
,
(80%)
(43).
TSC Vhl,
mTOR, polycystin-1 (PC1)
tuberin (TSC1/TCS2 complex) G1
. tuberin PC1
mTOR, ,
PC1
(40).
3: T 10
2. - .
(nephronophthisis, NPH)

-
,
( 2).
ESRD
(44). NPH .

,

.
, . ,
,
(situs inversus),
-
,
(40).
H NPH PHP1 (2q13)
nephrocystin-1 (20-40% ) (44). ,

12 PHP XPNPEP3
,
, NPH , ,
Potter .
NPH Senior-Loken ,
,
(40).

.
209

2: -

N (NPH) Y NPHP1 (2q13) Nephrocystin-1


NPHP2/INVS (9q31.1) Inversin
NPHP3 (3q22.1) Nephrocystin-3
,- NPHP4 (1p36.31) Nephrocystin-4
, NPHP5/IQCB1 IQCB1
, , (3q13.33) CEP290
NPHP6/CEP290 GLIS2
(12q21.2) RPGRIP1L
NPHP7/GLIS2 NEK8
(16p13.3) SDCCAG8
NPHP8/RPGRIP1L Meckelin
(16q12.2) IFT139
NPHP9/NEK8 (17q11.2) XPNPEP3
NPHP10/SDCCAG8
(1q43)
NPHP11/TMEM67
(8q22.1)
NPHP12/TTC21B
(2q24.3)
XPNPEP3/NPHPL1
(22q13.2)

. Senior-Lken NPHP1, INVS


+ (NPHP2), NPHP3,
(SLSN)
NPHP4, IQCB1
(NPHP5), CEP290
(NPHP6), SDCAAG8
(NPHP10)

. , UMOD (16p12.3) Uromodulin/


Tamm-Horsfall
(MCKD2), protein

(FJHN), ,
, ,
(GCKD)

(NPHP) .
,
Wnt/PCP Shh . (NPHP2)
- Wnt
- ,
PHP3 /
(), - -
( Ivemark) (45).
(Medullary Cystic Kidney Disease, MCKD)
, NPH.
UMOD (uro-
modulin Tamm-Horsfall ),
(40, 44). MCKD
2.
4: :
lumping split-
ting. Enza Maria Valente, 3.
5th Eur. Course in Clinical S -
Dysmorphology, Rome 2013) ,

210


. , ,
, - , (46).
,
- NPH
ARPKD ADPKD , -
- . BBS,
, ,
, .Hirschprung,
(40, 46).
18 BBS o
. 2003 BBS8
.
BBS1 10, MKS1/
BBS13 . eckel-Gruber CEP290/PHP6 (46).
BBS ,

(47).
BBS . Alstrm
, , , ,
( 3).
, .
BBS, . To
ALMS1, ,
(48).
,


(49).


(49).

4. -
Joubert (Joubert Syndrome, JS)
1:100000 . ,
, , -
( 4).
(50).
(CT/MRI)
(molartoothsign, MTS), ,
(50).
MTS
JS, (Joubert Syndrome Re-
lated Disorders, JSRD) (40,51). JSRD PH
. JSRD
, , ,
(51).
13 JS
.
CEP290/NPHP6 50% JS,
JSRD Leber, . Senior-Lken, NPH, .Meckel-Gruber,
BBS (Orofacio digital Syndrome, OFD) (2,51).
CEP290
CEP290,
211

3: -

. Bardet-Biedl (S) , , BBS1 (11q13.2) BBS1


, BBS2 (16q12.2) BBS2
, , BBS3/ARL6 (3q11.2) ARL6
, , , BBS4 (15q24.1) BBS4
BBS5 (2q31.1) BBS5
BBS6 /MKKS (20p12.2) MKKS
BBS7 (4q27) BBS7
BBS8/TTC8 (14q31.3) TTC8
BBS9 (7q14.3) PTHB1
BBS10 (12q21.2) BBS10
BBS11/TRIM32 TRIM32
(9q33.1) BBS12
BBS12 (4q27) MKS1
BBS13/MKS1 CEP290
(17q22) FRITZ
BBS14/CEP290 SDCCAG8
(12q21.32)
BBS15/WDPCP (2p15)
BBS16/SDCCAG8
(1q43)

. Alstrm , ALMS1 (2p13.1) ALMS1


,
,
,
, , , ,
, ,
,

. Ivemark -- NPHP3 (3q22.1) Nephrocystin-3


,
(/),
situsinversus, .

, GTP -
(RPGR), -4 (PHP4) -8 (NPHP8/RPGRIP1-
L), (52).
JSRD . Meckel-Gruber (MGS)
,
, / ,
(2,53).
, , , /
. CEP290, 8

MGS (null) (53) ( 4).

5.
O IFT

. Jeune,
( 5).
. Jeune (Jeune Asphyxiating Thoracic Dystrophy,
JATD),
,
. - ,

212

4: -

. Joubert (JBTS) INPP5E/JBTS1 (9q34.3) INPP5E


- TMEM216/JBTS2 TMEM216
(JSRD) (11q12.2) Jouberin
(molar- AHI1/JBTS3(6q23.3) Nephrocystin-1
toothsign ), . NPHP1/JBTS4 (2q13) CEP290
CEP290/JBTS5 Meckelin
, , , . (12q21.32) RPGRIP1L
, TMEM67/JBTS6 ARL13B
, (8q22.1) CC2D2A
, RPGRIP1L/JBTS7 OFD1
ductalplatemalformation, (16q12.2) KIF7
, ARL13B/JBTS8 (3q11.1) Tectonic 2
CC2D2A/JBTS9 Ataxin 10
(4p15.32)
OFD1/JBTS10 (Xp22.2)
KIF7 (15q26.1)
TCTN2 (12q24.31)
ATXN10 (22q13.31)

. Meckel (MKS) , MKS1 (17q22) MKS1


, TMEM216 /MKS2 TMEM216
, (11q13) Meckelin
ductalplatemalformation, TMEM67/MKS3 CEP290
, (8q22.1) RPGRIP1L
, . CEP290/MKS4 CC2D2A
, , (12q21.32) Nephrocystin-3
/ RPGRIP1L/MKS5 Tectonic 2
(16q12.2) B9D1
CC2D2A/MKS6
(4p15.32)
NPHP3(3q22.1)
TCTN2/MKS8
(12q24.31)
B9D1 (17p11.2)

, , -

. ,
. (2).
JATD
ESRD NPH,
,
(29). T ,
IFT80 Bealesetal
(54). IFT80 WDR56 IFT. JATD
,
TTC21B IFT139 IFT, DYNC2H1
-1 -2 NEK1
(54).
JATD . Ellis-van Creveld (EVC) -
,
, -
2/3 . EVC
EVC1 EVC2
Shh (55, 56).
JATD . EVC (I-
213

5: -

- 9D2 (19q13.2) B9D2


, OFD1 (Xp22.2) OFD1
1 /
(Orofaciodigitals., OFD1) , , ,
,

. - . IFT80 (3q25.33) IFT80/WDR56


DYNC2H1 (11q22.3) DYNC2H1
(shortribpolydactylys.) + NEK1 (4q33) NEK1
. Jeune/asphyxiating , TTC21B (2q24.3) IFT1 39/THM1
thoracic dystrophy, ATD) , WDR35 (2p24.1) IFT121/
, WDR35
, ductalplatemalforma-
tion

. Ellis-van Creveld EVC (4p16.2) EVC


(EVC) EVC2 (4p16.2) EVC2
,
,
,
,
,
, .

* : Weyers
acrodental dysostosis

K , IFT122 (3q21.3) IFT122/


(CED/Sensen- , WDR35 (2p24.1) WDR10
brenners.) ( , C14orf179 (14q24.3) IFT121/
-/ - WDR35
), IFT43

, ductalplatemal-
formation

IV) - (Short-Rib Polydactyly Syndrome,


SRPS).

.
(29,40). SRPS
. , Saldino-Noonan (SRPS )
torpedo-shaped , Majewski (SRPSII)
. JATD, SRPS EVC
(2,9,57).

,
(Cranioectodermal Dysplasia, CED). CED
, , ,
- ESRD.
3 IFT (58,59).

214

.

,
(28).
-
(8). ,

,
:
1. (genetic locus heterogene-
ity): .
NPHP1 , truncat-
ing NPHP6/CEP290 GS.
2. (multipleallelism): H truncat-
ing PHP3, NPHP6/CEP290, NPHP8, NPHP11/
MKS3 MGS ,
,
. Joubert(JS).
3. (modifiergenes):
NPHP1, NPHP6
NPHP8 .
4. (true oligogenicity):
BBS, -
,
(8).
,
,
. ,
truncating
,
,
. , MGS
RPKD, .Senior-Lken .
JS (8).

-
127 ,
.
-

. ,
(60).

DNA
Sanger. , (Next-Generation Sequenc-
ing, NGS),
. (multipleal-
lelism), ,
(40).
2003 BBS8,

.
-
,
, .
215

- /
(60).

DNA (DNA Damage Response, DDR).
F423, ATR NEK8/NPHP9 ,
, G2/M
stress (60).
, DDR
, DNA
. ,
DDR
.
,
,
mTOR Cdk
(61,62). ,

. ,
.
.
ADKPD ,
.

(loss-of-function ) / ,
(63).
: 1.
, BBS4
(knock-out), 2. ,
CEP290 zebrafish, 3.
RNA in vitro S1
U1RNA
(splice-donor sites) 4. DNA
(zinc finger nucleases, FN), DNA
. Usher (63).
,

DNA , DNA ,
,
- -(63).
,
,
,
.

1. Badano JL, Mitsuma N, Beales PL, Katsanis N. The ciliopathies: an emerging class of human
genetic disorders. Annu Rev Genomics Hum Genet 2006;7:125-148
2. Waters AM, Beales PL. Ciliopathies: an expanding disease spectrum. Pediatr Nephrol
2011;26:1731-1737
3. Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol 2002;3:813-825
4. Salathe M. Regulation of mammalian ciliary beating. Annu Rev Physiol 2007;69:401-422
5. Knowles MR, Daniels LA, Davis SD, Zariwala MA, and Leigh MW. Primary ciliary dyskine-
sia: Recent advances in diagnostics, genetics, and characterizationof clinical disease. Am J Respir
Crit Care Med 2013;188:913922
6. Bettencourt-Dias M, Hildebrandt F, Pellman D, Woods G, Godinho SA. Centrosomes and

216

cilia in human disease. Trends Genet 2011; 27:307-315


7. Goetz SC, Anderson KV. The primary cilium: a signalling center during vertebrate develop-
ment. Nat Rev Genet 2010;11:331-344
8. Hildenbrant F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med 2011; 364: 1533-1543
9. Nigg EA, Ralf JW. Centrioles, centrosomes and cilia in health and disease. Cell 2009;139:663-
678
10. Ishikawa H, Marshall WF. Ciliogenesis: building the cells antenna. Nat Rev Mol Cell Biol
2011; 12:222-234
11. Carroll TJ, Yu J. The kidney and planar cell polarity. Curr Top Dev Biol 2012; 101:185-212
12. Pedersen LB, Rosenbaum JL. Intraflagellar transport (IFT) role in ciliary assembly, resorp-
tion and signalling. Curr Top Dev Biol 2008; 85:23-61
13. Kobayashi T, Dynlacht BD. Regulating the transition from centriole to basal body. J Cell
Biol 2011; 193:435-444
14. Rosenbaum JL, Witman GB. Intraflagellar transport. Nat Rev Mol Cell Biol 2002; 3:813-
825
15. Singla V, Reiter JF. The primary cilium as the cells antenna; signaling at a sensory organelle.
Science 2006; 313; 629-633
16. Ross AJ, May-Simera H, Eichers ER, Kai M, Hill J, Jagger DJ et al. Disruption of Bar-
det-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat Genet
2005;37;1135-1140
17. Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and
principles.Genes Dev. 2001; 15:30593087
18. Louvi A, Artavanis-Tsakonas S. Notch signalling in vertebrate neural development. Nat Rev
Neurosci 2006 Feb;7:93-102
19. Li WX. Canonical and non-canonical JAK-STAT signaling. Trends Cell Biol 2008
Nov;18:545-551
20. Hassan B, Akcakanat A, Holder AM, Meric-Bernstam F. Targeting the PI3-kinase/Akt/
mTOR signaling pathway. Surg Oncol Clin N Am 2013 Oct;22:641-664
21. Wang Z, Ahmad A, Li Y, Kong D, Azmi AS, Banerjee S et al. Emerging roles of PDGF-
D signaling pathway in tumor development and progression. Biochim Biophys Acta 2010
Aug;1806:122-130
22. Goggolidou P. Wnt and planar cell polarity signaling in cystic renal disease. Organogenesis
2014 Jan 1;10:86-95
23. Wei Q, Zhang Y, Li Y, Zhang Q, Ling K, Hu J. The BBSome controls IFT assembly and
turnaround in cilia. Nat Cell Biol 2012 Sep;14(9):950-957
24. Milenkovic L, Scott MP, Rohatdi R. Lateral transport of Smoothened from the plasma mem-
brane to the membrane of the cilium. J Cell Biol; 187:365-374
25. Huber TB, Walz G, Kuehn EW. mTOR and rapamycin in the kidney: signaling and thera-
peutic implications beyond immunosuppression. Kidney Int 2011 Mar;79:502-11
26. Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis
of Bardet-Biedl syndrome: results of a population survey. J Med Genet 1999;6: 437-446
27. Xing DJ, Zhang HX, Huang N, Wu KC, Huang XF, Huang F et al. Comprehensive molecu-
lar diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing. PLoS
One 2014 Mar 7;9:e90599
28. Zaki MS, Sattar S, Massoudi RA, Gleeson JG.. Co-occurrence of distinct ciliopathy diseases
in single families suggests genetic modifiers. Am J Med Genet Part A 2011;155:30423049
29. Baker K, Beales PL. Making sense of cilia in disease: the human ciliopathies. Am J Med
Genet Part C (Seminars in Medical Genetics) 2009;151C:281-295
30. Gascue C, Katsanis N, Badano JL. Cystic diseases of the kidney: ciliary dysfunction and
cystogenic mechanisms. Pediatr Nephrol 2011;26: 1181-1195
31. Steinman TI. Polycystic kidney disease: a 2011 update. Curr Opin Nephrol Hypertens.
2012;21:189-194
32. Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM et al. Magnet-
ic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney
disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort.
217

Clin J Am Soc Nephrol 2006;1:64-69


33. Kang YR, Ahn JH, Kim KH, Choi YM, Choi J, Park JR. Multiple cardiovascular manifesta-
tions in a patient with autosomal dominant polycystic kidney disease. J Cardiovasc Ultrasound
2014;22:144-147
34. Pirson Y. Extrarenal manifestations of autosomal dominant polycystic kidney disease. Adv
Chronic Kidney Dis 2010;17:173-180
35. Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kid-
ney Int 2009;76:149-168
36. Harris PC, Bae KT, Rosetti S, Torres VE, Grantham JJ, Chapman AB et al. Cyst number
but not the rate of cystic growth is associated with the mutated gene in autosomal dominant
polycystic kidney disease. J Am Soc Nephrol 2006;17:3013-3019
37. Ward CJ, Hogan MC, Rossetti S, Walker D, Sneddon T, Wang X et al. The gene mutated
in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet
2002;30:259-269
38. Turkbey B, Ocak I, Daryanani K, Font-Montgomery E, Lukose L, Bryant J et al. Autosomal
recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF). Pediatr Ra-
diol 2009 ;39:100-111
39. Wang S, Luo Y, Wilson PD, Witman GB, Zhou J. The autosomal recessive polycystic kidney
disease protein is localized to primary cilia, with concentration in the basal body area. J Am Soc
Nephrol 2004 Mar;15:592-602
40. Bergmann C. Educational paper: Ciliopathies. Eur J Pediatr 2012;171:1285-1300
41. Cnossen WR, Drenth JP. Polycystic liver disease: an overview of pathogenesis, clinical mani-
festations and management. Orphanet J Rare Dis 2014;9:69
42. Chou A, Toon C, Pickett J, Gill AJ. von Hippel-Lindau syndrome. Front Horm Res
2013;41:30-49
43. Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med
2006;355:1345-1356
44. Hildenbradt F, Zhou W. Nephronopthisis-associated ciliopathies. J Am Soc Nephrol
2007;18:1855-1871
45. Simons M, Walz G. Polycystic kidney disease: cell division without a c(l)ue? Kidney Int
2006;70:854-864
46. Zaghloul NA, Katsanis N. Mechanistic insights into Bardet-Biedl syndrome, a model cili-
opathy. J Clin Invest 2009;119: 428-437
47. Leitch C, Zaghloul NA, Davis EE, Stoetzel C, Diaz-Font A, Rix S et al. Hypomorphic muta-
tions in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat Genet
2008;40:443-448
48. Marshall JD, Beck S, Maffei P, Naggert JK. Alstrm syndrome. Eur J Hum Genet
2007;15:1193-1202
49. Girard D1, Petrovsky N. Alstrm syndrome: insights into the pathogenesis of metabolic
disorders. Nat Rev Endocrinol 2011;7:77-88
50. Parisi MA. Clinical and molecular features of Joubert Syndrome and related disorders. Am J
Med Genet C Semin Med Genet 2009;151C:326-340
51. Brancati F, Dallapiccola B, Valente EM. Joubert Syndrome and related disorders. Orphanet
J Rare Dis 2010;5:20
52. Coppieters F, Lefever S, Leroy BP, De Baere E. CEP290, a gene with many faces: mutation
overview and presentation of CEP290base. Hum Mutat 2010;31:1097-1108
53. Bergmann C, Fliegauf M, Brchle NO, Frank V, Olbrich H, Kirschner J et al. Loss of
nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs in-
versus, and renal-hepatic-pancreatic dysplasia. Am J Hum Genet 2008 Apr;82:959-970
54. Beales PL, Bland E, Tobin JL, Baccelli C, Tuysuz B, Hill J et al. IFT80 which encodes a
consrved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy.
Nat Genet 2007;39:727-729
55. Brugmann SA, Cordero DR, Helms JA. Craniofacial ciliopathies: A new classification for
craniofacial disorders. Am J Med Genet Part A 2010;152A:2995-3006
56. Galdzicka M, Patnala S, Hirshman MG, Cai JF, Nitowsky H, Egeland JA et al. A new gene

218

EVC2, is mutated in Ellis-van-Creveld syndrome. Mol Genet Metab 2002;77:291-295


57. Elcioglu NH, Hall CM. Diagnostic dilemmas in the short-rib-polydactyly syndrome group.
Am J Med Genet 2002;111:392-400
58. Konstantinidou AE, Fryssira H, Sifakis S, Karadimas C, Kaminopetros P, Agrogiannis G et al.
Cranioectodermal dysplasia: A probable ciliopathy. Am J Med Genet Part A 2009;149A:2206-
2211
59. Hoffer JL, Fryssira H, Konstantinidou AE, Ropers HH, Tzschach A. Novel WDR35 mu-
tations in patients with cranioectodermal dysplasia (Sensenbrenner syndrome). Clin Genet
2013;83:92-95
60. Fry AM, Leaper MJ, Bayliss R. The primary cilium: guardian of organ development and
homeostasis. Organogenesis 2014;10:62-68
61. Wahl PR, Serra AL, Le Hir M, Molle KD, Hall MN, Wthrich RP. Inhibition of mTOR
with sirolimus slows disease progression in Han:SPRD rats with autosomal dominant polycystic
kidney disease (ADPKD). Nephrol Dial Transplant 2006 Mar;21:598-604
62. Bukanov NO, Moreno SE, Natoli TA, Rogers KA, Smith LA, Ledbetter SR et al. CDK in-
hibitors R-roscovitine and S-CR8 effectively block renal and hepatic cystogenesis in an ortholo-
gous model of ADPKD. Cell Cycle 2012;11:4040-4046
63. McIntyre JC, Williams CL, Martens JR. Smelling the roses and seeing the light: gene therapy
for ciliopathies. Trends Biotechnol 2013;31:355-363
219

220

E A

15 , 57400,

e-mail: mtsigga@nutr.

: teithe.gr

ADONUT
, , , -
, & ADONUT

ADONUT: , , ,
, , , , ,
, , , -, ,
, , , , ,
, , , , ,
, , , , ,
, , , , , ,
, - , , , ,
, , , , ,
, , , , , ,
, , , , ,
, , , ,
, , , , , ,
, , , ,
, - , - , , &


:
.
15 .
: 3519 3509 15
318 .
(), .
International Obesity Task Force,
Fernandez.
:
(66.1%), 22.1% , 7.3% ,
4.6% .
35.0% 23.6% ,
.
. 9.5%,
10.1% , 9.0%.
.

:

,
15 . &
,
: , , , ,

ORIGINAL ARTICLES

221

Correspondence
Maria Tsigga
Prevalence of simple and abdomi-
Sindos, GR57400, Thes-
saloniki
e-mail: mtsigga@nutr.
nal obesity among 15 year old ado-
teithe.gr
lescents in Greece: results from the
ADONUT study
Maria Grammatikopoulou, Dimitrios Poulimeneas, Konstantina Gerothanasi, Efstratios Kiranas,
Maria Tsigga & ADONUT Study Group

ADONUT Study Group: Calliope Aberiadou, EfrosyniAlexopoulou, DemetraApostolou, IoannaBozouri, Stel-


la Chortiatinou, Olympia-Brenda Christodoulou, Maria Dalakoglou, PelagiaDamianou, Anastasia Daviti,
Leonidas Dimitrakopoulos, KyriakiDimitriou-Kouspou, NikolaosDrougkas, AikateriniEfstathiadi, Konstanti-
nosFamisis, Irene Foukou, Hermione Hatziaggelousi, DimitriosHatzipetrou, ArgyroHatzivasileiou, Diaman-
toulaHoremi, Thessalia-VaiaHroni, IoannisIdreos, Sofia Thanasogeorgou, Irene Theodoridou, Konstantina
Theohari, IoannisKafantaris, AimiliaKakali, Marina Kalli, MeropiKalli, KonstantinosKalpakis, Christina
Karabaliou, PanagiotaKarabela, AikateriniKaragkiozaki, Maria Karaventza, Georgia Kazasi, Maria Kiokaki,
PolykseniKokka, Nikolaos Kokkinos, StamatiaKonstanta, EleniKotseridi, AhmetKourou, FotiniKsenaki, Anna
Kyrgiou, Smaro-Maria Lazoglou, EleniMakantasi, ElianaMameka, Olga Maridaki, AikateriniMourati-
dou, Artemis Niarchou, Kyriaki Papa, Sofia Papagiannidou, KonstantinosPapathanasiou, AikateriniPappa,
Charoula Pavli, AidonitsaPavlidi, Magdalene Pipeki, Athena Pourlioti, CharaPsachoula, Maria Psalidakou,
Vera Psomopoulou, EleniRizou, EleniRomba, GeorgiosSbyrakis, SpyridoulaSoulaidopoulou, Maria Spanoudaki,
AikateriniTriantafyllidou, VasilikiTriantafyllopoulou, Anastasia Troumpouki, KonstantiniaTsami, Georgia
Tserepi, MarilenaTsivgouli, DespoinaValaora, Maria Verykokkou, Anna Vlahou, Anastasia Voulgaridou and
Maria Zymara

Abstract
Background: Adolescent health is of cardinal importance, as a plethora of adulthood diseases
are actually consolidated during adolescence. The aim of this study is to assess the prevalence of
simple and abdominal obesity among 15-year-old Greek adolescents.
Methods: A nationally representative sample of 7028 adolescents, aged 12-19 years old, was re-
cruited from schools throughout the country during 2010-2012. Body weight, stature and waist
circumference were measured. The prevalence of each weight category was defined according to
the International Obesity Task Force criteria and abdominal obesity was diagnosed according to
the International Diabetes Federation.
Results: The majority of the participants were normoweight (66.1%), 22.1% were overweight,
7.3% obese, and the remaining 4.6% were underweight. Overweight including obesity reached
35% among boys and 23.6% among girls, with increased prevalence in Thrace and Thessaly.
High prevalence of underweight was observed in Epirus. In the total sample 9.5% was diagnosed
with abdominal obesity, including 10.1% of the girls and 9.0% of the boys. Central obesity
reached of the population among girls in Thrace and Thessaly.
Maria Grammatikopoulou Conclusions: Differences are observed in the weight status tiers between different geographical
Dimitrios Poulimeneas regions of the country, among 15-year-old adolescents. Spatial analysis of the data provide a bet-
Konstantina Gerothanasi
ter approach in highlighting areas in need of intervention.
Efstratios Kiranas
Maria Tsigga
Department of Nutrition Key words: Overweight, obese, waist circumference, Greek, adolescents
& Dietetics, Alexander
Technological Educational
Institute, Thessaloniki

222


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

. ,

() ,
,
, (2,3).
,
. () (4)
11 (2004) ADONUT 2010-12 (5).
,
.
(6), ,
15
.
17.5
15-17 ,
15 (7,8). E,
15
(9).

15 ,
.



3519 3509 15 318
,
. ,
,

(5).


,
()
, / .

(MIS80413).


, ,
.
SECA 874 SECA 214 (Seca GmbH &
Co., Hamburg, Germany).
.
() International Obesity Task Force (IOTF) (10,11).

(12).
National Heart, Lung, and Blood Institutes (13)
Fernandez
223

(14) International Diabetes Federation (IDF) (15).


PASW Statistics 18 (SPSS
Inc., HongKong).
x2, (Prevalence Ratio, PR)
(16,17)
(95% Confidence Intervals).


1
. ,
(3.8%) (PR:0.7, CI:0.6-0.9,p0.001) (6.1%) (R:0.9, CI:0.8-
0.9,p0.001) (26.2%) (PR:1.5, CI:1.4-1.6,
p0.001) (8.8%) (PR:1.5, CI:1.3-1.8, p0.001) .
5.3%,
(71.2%), 17.9% 5.7% . ,
(PR:0.3, CI:0.1-0.7, p0.002)
(PR:2.6, CI:1.2-5.7, p0.016).
, , ,
.
(PR:1.7, CI:1.1-2.7, p0.015, PR:1.7, CI:1.4-2.1, p0.001)
(PR:0.8, CI:0.8-0.9, p0.001), . ,

(PR:0.8, CI:0.6-0.9, p0.002),
(PR:2.1, CI:1.3-3.4, p0.001).

1: , 15-16 ,


N n % 95% CI n % 95% CI n % 95% CI n % 95% CI

192 3 1.6 -0.2-3.3 120 62.5 55.6-69.4 55 28.6 22.2-35.1 14 7.3 3.6-11.0

1636 51 3.1 2.3-4.0 1002 61.2 58.9-63.6 415 25.4 23.3-27.5 168 10.3 8.8-11.7

148 6 4.1 0.8-7.3 92 62.2 54.370.1 31 20.9 14.3-27.6 19 12.8 7.4-18.3

374 12 3.2 1.4-5.0 238 63.6 58.7-68.5 97 25.9 21.5- 30.4 27 7.2 4.6-9.9

863 52 6.0 4.4-7.6 511 59.2 55.9-62.5 237 27.5 24.5-30.4 63 7.3 5.6-9

106 2 1.9 -0.7-4.5 75 70.8 62.0-79.6 23 21.7 13.7-29.7 6 5.7 1.2-10.1

16 1 6.3 -7.1-19.6 9 56.3 28.9-83.6 5 31.3 5.7-56.8 1 6.3 -7.1-19.6

49 1 2.0 -2.1-6.1 27 55.1 40.7-69.5 17 34.7 20.9-48.5 4 8.2 0.2-16.1

135 7 5.2 1.4-9.0 76 56.3 47.8-64.8 43 31.9 23.9-39.8 9 6.7 2.4-10.9

3519 135 3.8 3.2-4.5 2150 61.1 59.5-62.7 923 26.2 24.8-27.7 311 8.8 7.9-9.8

224

1: , 15-16 ,


N n % 95% CI n % 95% CI n % 95% CI n % 95% CI

192 11* 5.7 2.4-9.1 125 65.1 58.3-71.9 43 22.4 16.5-28.4 13 6.8 3.2-10.4

1738 95*** 5.5 4.4-6.5 1261*** 72.6 70.5-74.7 295*** 17.0 15.2-18.7 87*** 5.0 4.0-6.0

159 23** 14.5 8.9-20.0 98 61.6 54-69.3 30 18.9 12.7-25.0 8* 5.0 1.6-8.5

334 11 3.3 1.4-5.2 227 68.0 62.9-73.0 82 24.6 19.9-29.2 14 4.2 2.0-6.4

803 28** 3.5 2.2-4.8 577*** 71.9 68.7-75.0 129*** 16.1 13.5-18.6 69 8.6 6.7-10.5

104 4 3.8 0.9-7.6 77 74.0 65.5-82.6 20 19.2 11.5-26.9 3 2.9 -0.4-6.2

9 1 11.1 -14.5-36.7 7 77.8 43.9-111.7 1 11.1 -14.5-36.7 0 0.0 -

30 1 3.3 -3.5-10.2 22 73.3 56.5-90.1 6 20.0 4.8-35.2 1 3.3 -3.5-10.2

140 9 6.4 2.3-10.5 104** 74.3 67-81.6 21*** 15.0 9.0-21.0 6 4.3 0.9-7.7

3509 185** 5.3 4.5-6.0 2498*** 71.2 69.7-72.7 627*** 17.9 16.6-19.1 201*** 5.7 5.0-6.5

CI: Confidence Intervals ( )


* (* p0.05, ** p0.01, *** p0.001)

2
. , 9.0% 10.2%
. ,
(PR:0.6, CI:0.4-
0.8, PR:0.4, CI:0.2-0.6, p0.001).
,
, , ,
.
1
, , 15 .
,
27.4-42.9%,
. 11.1-29.2%
.
3
. 7028 15 , 4.6% , 66.1%
, 22.1% 7.3%
. 9.5% ,
4.4% .
( ) (PR:1.6, CI:1.3-2.0,p0.001)
.
1:

(
15 ) ()
(66.1%), 22.1% , 7.3% , 4.6% (), 15-16
,
225

.
9.5%.

2: 15-16
,


N n % 95% CI N N % 95% CI

192 17 8.9 4.8-12.9 192 46*** 24.0 17.9-30.1

1636 137 8.4 7.0-9.7 1738 142 8.2 6.9-9.5

148 12 8.1 3.7-12.6 159 13 8.2 3.9-12.5

374 57 15.2 11.6- 18.9 334 89*** 26.6 21.9-31.4

863 76 8.8 6.9-10.7 803 53 6.6 4.9-8.3

106 3 2.8 -0.4-6.0 104 1 1.0 -1.0-2.9

16 0 0.0 - 9 0 0.0 -

49 4 8.2 0.2-16.1 30 1 3.3 -3.5-10.2

135 11 8.1 3.5-12.8 140 8 5.7 1.8-9.6

3519 317 9.0 8.1-10.0 3509 353 10.1 9.1-11.1

CI: Confidence Intervals ( )


*** (p0.001)

,
35.0%, 23.6%. 12 ,
(4)
15 (35.8%),
(16.4%) ( 4). ,
, . (4),
2003, (18)
15 ,
(25.9 7.6% ).

. ,
.
, 2004, 15
, (19) 25.8% 16.3%
, .
, ...
(20)
,
10-15 , 2002 2010.
, .
,
,
. , ( 1)
. ,

226

32.5%.
,
.
, . ,
31.1%, 28.8%,

, (21) 15-17 (35.5%).

3: ,


N n % 95% CI n % 95% CI n % 95% CI n %

384 14 3.6 1.8-5.5 245 63.8 59.0-68.6 98 25.5 21.1-29.9 27 7.0

3374 146 4.3 3.6-5.0 2263 67.1 65.5-68.7 710 21.0 19.7-22.4 255 7.6

307 29 9.4 6.2-12.7 190 61.9 56.4-67.4 61 19.9 15.4-24.4 27 8.8

708 23 3.2 1.9-4.6 465 65.7 62.2-69.2 179 25.3 22.1-28.5 41 5.8

1666 80 4.8 3.8-5.8 1088 65.3 63.0-67.6 366 22.0 20.0-24.0 132 7.9

210 6 2.9 0.6-5.1 152 72.4 66.3-78.5 43 20.5 15.0-26.0 9 4.3

25 2 8.0 -3.4-19.4 16 64.0 43.8-84.2 6 24.0 6.0-42.0 1 4.0

79 2 2.5 -1.0-6.1 49 62.0 51.1-73.0 23 29.1 18.9-39.4 5 6.3

275 16 5.8 3.0-8.6 180 65.5 59.8-71.1 64 23.3 18.2-28.3 15 5.5

7028 320 4.6 4.1-5.0 4648 66.1 65.0-67.2 1550 22.1 21.1-23.0 512 7.3

CI: Confidence Intervals ( )

4: , 15-16 ,



() ()
N % % % + N % % % +

(5) 2010-2012 15-16 3519 26.3 8.8 35.1 3509 17.9*** 5.7*** 23.6*** 7

(4) 2003 15-16 2293 30.1 5.7 35.8 2598 14.2*** 2.2*** 16.4*** 4

(19) 2004-2005 15 174 19.5 6.3 25.8 166 15.1 1.2* 16.3

(18) 2003 15 23.0 2.9 25.9 6.2 1.4 7.6 1

(18) 2003 15 18.8 6.2 25.0 5.6 1.7 7.3 1

(20) 2002 10-15 1870 20.3 1937 10.8*** 3

2006 10-15 1746 24.5 1944 13.1*** 3

2010 10-15 2380 26.4 2519 15.2*** 4

: , : , : , :

* (*** p0.001. *p0.05)
IOTF: International Obesity Task Force,CDC: Centre for Disease Control
227

&

95% CI n % 95% CI n % 95% CI

4.5-9.6 30 7.8 5.1-10.5 9 2.3 0.8-3.9

6.7-8.5 279 8.3 7.3-9.2 162 4.8 4.1-5.5

5.6-12.0 25 8.1 5.1-11.2 18 5.9 3.2-8.5

4.1-7.5 146 20.6 17.6-23.6 31 4.4 2.9-5.9

6.6-9.2 129 7.7 6.4-9.0 59 3.5 2.7-4.4

1.5-7.0 4 1.9 0.0-3.8 3 1.4 -0.2-3.1

-4.3-12.3 0 0.0 - 0 0.0 -

0.8-11.8 5 6.3 0.8-11.8 4 5.1 0.1-10.0

2.8-8.2 19 6.9 3.9-9.9 11 4.0 1.7-6.3

6.7-7.9 670 9.5 8.9-10.2 306 4.4 3.9-4.8




N % % % +

7028 22.1 7.25 29.4 IOTF

4891 21.7 3.8 25.5 IOTF

340 17.4 3.8 21.2 IOTF

1322 IOTF

1322 CDC

3807 15.5 IOTF

3690 18.5 IOTF

4899 20.7 IOTF


228

IOTF
( 5), 15
.
, , , , , ,
15 20% (22-28,34-35,38).

5: 15 , IOTF (10,11)



()
N % + % N

(22) 2012-4 35 2.9 25.7 36

(23) 2001-2 1051 - 22 935

(23) 2001-2 . 198 - 25 231

, , ,
(24) 2000-2 301 4 26.6 340
,

(25) 2002 521 - 21.9 653

(26) 2004 5 17.6

(26) 2006 3.1 27.5

(27) 1999-2000 105 - 20 101

(28) 2005-6 - 31.6

(29) 2003-6 238 10.9 248

(30) 2003 - 15.4

(31) 2008-9 - 14.7

(32) 501 6 17.8 572

-, ,
(33) 2005 428 - 11.9 485
, ,

(34) 2008 1387 - 20.8 1414

(35) 2008 - 26.1

(36) 2001 75 20 11.9 66

(37) 2002 849 - 17.9 860

(37) 2006 748 - 19.9 854

(37) 2010 943 - 17.5 1026

: , : , :
229

% + % N % + %

22.2 16.6 71 12.7 21.1

- 22 1986 - 22.0

- 23 429 - 23.9

4.1 17.1 641 4.1 21.5

- 8.4 1174 - 14.4

14.5 9 1160 9.7 13.3

14.1 12.2 1078 8.7 19.7

- 15.9 206 - 18.0

- 13.0 - -

- 7.3 486 - 9.1

- 17.2 1521 - -

- 13.8 - -

11.5 14.5 1073 8.9 16.0

- 11.9 913 - 11.4

- 19.4 2801 - 20.1

- 35.9 -

6.1 13.6 141 13.5 12.8

- 9.4 1709 - 13.6

- 12.4 1602 - 15.9

- 11 1969 - 14.1

230


(, , , N, ,
) (29-33,36,37,39-40). , (23)
() (35) 20%.
ADONUT
(5).
(6.3%)
(14.5%). ( 5),
(22),
(23) . ,
(36),
, , (22,24,26,32)
.
,
, (36),
(23), () (38)
(34), .

.

15 , , (42). ,
9.5-14.5, 15
,
,
.
(4,5),
(12, 38, 42).
O 9.5%,
10.1% , 9.0%.
(4), 23.1% 15.6%
,
. ,

(43). ,
,
.
, ,
15
.
(15.2
26.6% ), (8.9
24.0% ).
,
(43). ,
(4,5),
(45). IDF (15),

. ,
4.4% .

, . ,

,
.
15 ,
231

.

15 (45),

.
15 ,
.

,

.


,
.

2015,
.

1. Patton GC, Coffey C, Cappa C, Currie D, Riley L, Gore F, et al. Health of the worlds ado-
lescents: a synthesis of internationally comparable data. Lancet 2012;379:1665-1675.
2. Bibbins-Domingo K, Coxson P, Pletcher MJ, Lightwood J, Goldman L. Adolescent Over-
weight and Future Adult Coronary Heart Disease. NEngl J Med 2007;357:2371-2379.
3. Dietz DW. Health Consequences of Obesity in Youth: Childhood Predictors of Adult Dis-
ease. Pediatrics 1998;101(S2):518-525.
4. Tzotzas T, Kapantais E, Tziomalos K, Ioannidis I, Mortoglou A, Bakatselos S, et al. Epide-
miological survey for the prevalence of overweight and abdominal obesity in Greek adolescents.
Obesity (Silver Spring) 2008;16:17181722.
5. Grammatikopoulou MG, Poulimeneas D, Gounitsioti IS, et al. Prevalence of Simple and
Abdominal Obesity in Greek Adolescents: The ADONUT Study. ClinObes 2014;4:303-308.
6. Lissau I, Overpeck MD, Ruan WJ, Due P, Holstein B, Hediger M, et al. Body mass index and
overweight in adolescents in 13 European countries, Israel and the United States. Arch Pediat-
rAdolesc Med 2004;158:2733.
7. Velasquez-Mieyer P, Perez-Faustinelli S, Cowan PA. Identifying Children at Risk for Obesity,
Type 2 Diabetes, and Cardiovascular Disease. Diabetes Spectr 2005;18:213-220.
8. Field AE, Cook NR, Gillman MW. Weight status in childhood as a predictor of becoming
overweight or hypertensive in early adulthood. Obes Res 2005;13:163-169.
9. Hulens M, Beuven G, Claessens AL, Lefevre J, Thomis M, Philippaerts R, et al. Trends in BMI
among Belgian children, adolescents and adults from 1969 to 1996. Int J Obes 2001;25:395-
399.
10. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child
overweight and obesity worldwide: international survey. BMJ2000;320:12401243.
11. Cole TJ, Flegal KM, Nicholls D, Jackson AA. Body mass index cut offs to define thinness in
children and adolescents: international survey. BMJ2007;335:194.
12. Lien N, Henriksen HB, Nymoen LL, Wind M, Klepp KI. Availability of data assessing the
prevalence and trends of overweight and obesity among European adolescents. Public Health
Nutr2010;13:16801687.
13. National Heart, Lung, and Blood Institutes (NHLBI) Obesity Education Initiative. The
Practical Guide. 1 Identification, Evaluation, and Treatment of Overweight and Obesity in
Adults. North American Association for the Study of Obesity. NIH, 2000. [WWW document].
URL http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf (accessed July 16, 2015).
14. Fernandez JR, Redden D, Pietrobelli A,Allison DB. Waist circumference percentiles in na-

232

tionally representative samples of African-American, European-American, and Mexican-Ameri-


can children and adolescents. J Pediatr2004;145:439444.
15. International Diabetes Federation. IDF consensus definition of metabolic syndrome in chil-
dren and adolescents. International Diabetes Federation: Brussels, 2007.
16. McNutt L-A, Wu C, Xue X, Hafner. Estimating the Relative Risk in Cohort Studies and
Clinical Trials of Common Outcomes. Am J Epidemiol 2003;157:940-943.
17. Santos CA, Fiaccone RL, Oliveira NF, Cunha S, Barreto ML, Carmo MB, et al. Estimat-
ing adjusted prevalence ratio in clustered cross-sectional epidemiological data. BMC Med Res
Methodol 2008;8:80.
18. Karayiannis D, Yannakoulia , Terzidou , Sidossis LS, Kokkevi A. Prevalence of
Overweight and Obesity in Greek School-Aged Children and Adolescents. Eur J ClinNutr
2003;57:1189-1192.
19. Kosti RI, Panagiotakos DB, Mihas CC, Alevizos A, Zampelas A, Mariolis A, et al. Dietary
Habits. Physical Activity and Prevalence of Overweight/Obesity among Adolescents in Greece:
The Vyronas Study. Med SciMonit 2007;13:CR437-444.
20. Ahluwalia N, Dalmasso P, Rasmussen M, Lipsky L, Currie C, Haug E, et al. Trends in Over-
weight Prevalence among 11-, 13- and 15-Year-Olds in 25 Countries in Europe, Canada and
USA from 2002 to 2010. Eur J Public Health 2015;25(S2):28-32.
21. Tsartsali PK, Thompson JL, Jago R. Increased knowledge predicts greater adherence to the
Mediterranean diet in Greek adolescents. Public Health Nutr 2009;12:208-213.
22. Mladenova S, Andreenko E. Prevalence of underweight, overweight, general and central obe-
sity among 8-15- years old Bulgarian children and adolescents (Smolyan region, 2012-2014).
NutrHosp 2015;31:2419-2427.
23. Whelton H, Harrington J, Crowley E, Kelleher V, Cronin M, Perry IJ. Prevalence of over-
weight and obesity on the island of Ireland: results from the North South Survey of Childrens
Height, Weight and Body Mass Index, 2002. BMC Public Health2007;7:187.
24. Artero EG, Espaa-Romero V, Ortega FB, Jimnez-Pavn D, Ruiz JR, Vicente-Rodrguez
G, et al. Health-related fitness in adolescents: underweight, and not only overweight, as an influ-
encing factor. The AVENA study. Scand J Med Sci Sports2010;20:418-427.
25. Vieno A, Santinello M, Martini MC. Epidemiology of overweight and obesity among Italian
early adolescents: relation with physical activity and sedentary behaviour. EpidemiolPsichiatrSoc
2005;14:100-7.
26. Lazzeri G, Rossi S, Pammolli A, Pilato V, Pozzi T, Giacchi MV. Underweight and over-
weight among children and adolescents in Tuscany (Italy). Prevalence and short-term trends. J
Prev Med Hyg 2008;49:13-21.
27. Savva SC, Kourides Y, Tornaritis M, Epiphaniou-Savva M, Chadjigeorgiou C, Kafatos A.
Obesity in children and adolescents in Cyprus. Prevalence and predisposing factors. Int J Obes
2002;26:10361045.
28. . 12-17
. , &.
&. , 2007.
29. Jlusson PB, Eide GE, Roelants M, Waaler PE, Hauspie R, Bjerknes R. Overweight and
obesity in Norwegian children: prevalence and socio-demographic risk factors.Acta Paediatr
2010;99:900-905.
30. Van den Hurk, Van DommelenP, Van Buuren S, Verkerk PH, HiraSing RA. Prevalence of
overweight and obesity in the Netherlands in 2003 compared to 1980 and 1997. Arch Dis Child
2007;92:992995.
31. Schnbeck Y, Talma H, van Dommelen P, Bakker B, Buitendijk S, HiraSing RA, et al.
Increase in prevalence of overweight in Dutch children and adolescents: a comparison of nation-
wide growth studies in 1980, 1997 and 2009.PLoS One 2011;6:e27608.
32. Kantanista A, Osinski W. Underweight in 14 to 16 year-old girls and boys: prevalence and
associations with physical activity and sedentary activities. Ann Agric Environ Med 2014;21:114
119.
33. Jodkowska M, Oblacinska A, Tabak I. Overweight and obesity among adolescents in Poland:
gender and regional differences. Public Health Nutr 2010;3:16881692.
233

34. Sardinha LB, Santos R, Vale S, Silva AM, Ferreira JP, Raimundo AM, et al. Prevalence
of overweight and obesity among Portuguese youth: A study in a representative sample of
1018-year-old children and adolescents. Int J PediatrObes2011;6:e124-128.
35. Santos R, Aires L, Santos P, Ribeiro JC, Mota J.Prevalence of overweight and obesity in a
Portuguese sample of adults: results from the Azorean Physical Activity and Health Study. Am J
Hum Biol 2008;20:78-85.
36. ner N, Vatansever , Sari A, Ekuklu G, Gzel A, Karasalihoglu S, Boris NW. Prevalence of
underweight, overweight and obesity in Turkish adolescents. Swiss Med Wkly 2004;134:529
533.
37. Ojala K, Tynjl J, Vlimaa R, Villberg J, Kannas L. Overweight Adolescents Self-Perceived
Weight and Weight Control Behaviour: HBSC Study in Finland 19942010. J Obes. 2012;
2012:180176.
38. Baratta R, Degano C, Leonardi D, Vigneri R, Frittitta L. High prevalence of overweight and
obesity in 11e15-year-old children from Sicily. NutrMetabCardiovasc Dis 2006;16:249-255.
39. Currie C, Zanotti C, Morgan A, Currie D, de Looze M, Roberts C, et al, eds. Social determi-
nants of health and well-being among young people: Health Behaviour in School-aged Children
(HBSC) study: international report from the 2009/2010 survey. Copenhagen, WHO Regional
Office for Europe, 2012 (Health Policy for Children and Adolescents, No. 6) (http://www.euro.
who.int/__data/assets/pdf_file/0003/163857/Social-determinants-of-health-and-well-being-
among-young-people.pdf, accessed 21 September 2015).
40. Vaezghasemi M, Lindkvist M, Ivarsson A,Eurenius E. Overweight and lifestyle among 1315
year olds: A cross-sectional study in northern Sweden. Scand J Public Health2012;40:221228.
41. Tanner JM. Growth at Adolescence, 2nd ed. Oxford, Blackwell Scientific Publishers, 1962.
42. de Gouw L, Klepp K-I, Vignerov J, Lien N, Steenhuis IH, Wind M, et al. Associations
between diet and (in)activity behaviours with overweight and obesity among 10 to 18 year old
Czech Republic adolescents. Public Health Nutr2010;13:17011707.
43. de Moraes AC, Fadoni RP, Ricardi LM, Souza TC, Rosaneli CF, Nakashima AT, et al.
Prevalence of abdominal obesity in adolescents: a systematic review. ObesRev 2011;12:6977.
44. Ekelund U, Anderssen S, Andersen LB, Riddoch CJ, Sardinha LB, Luan J, et al. Prevalence
and correlates of the metabolic syndrome in a population-based sample of European youth. Am
J Clin Nutr 2009;89:90-96.
45. Hakanen M, Lagstrm H, Pahkala K, Sillanmki L, Saarinen M, Niinikoski H, et al. Dietary
and lifestyle counseling reduces the clustering of overweight- related cardiometabolic risk factors
in adolescents. Acta Paediatr 2010;99:888895.

234

- 32,
,
72100

e-mail: efi.tavladaki@
gmail.com
. 6945553102

, , , ,


:
, 22

. (,
) , ,
.
-: -
18 , 15 20
SIRS. 27
.
24 ().
:
.
(PosthocanalysesSSvs. H, SIRSvs. H: p<0.001).
(PosthocanalysesSSvs. H,
SIRSvs. H: p<0.004).
(p<0,05)
APACHE II CRP (p<0,05).
:
.

.

: , , SIRS, ,




,




,
,



NeoLab,
ORIGINAL ARTICLES

235

Correspondence
Theonymfi Tavladaki
Early changes of amino acids in criti-
Anapafseos 32, Agios
Nikolaos, Crete, 72100
e-mail: efi.tavladaki@
cal ill children dependent on disease
gmail.com
. +306945553102 severity
Theonymfi Tavladaki, Anna Maria Spanaki, Helen Dimitriou, EvaggelosPapakonstantinou, George
Briassoulis

Abstract
Background: Since the metabolism of amino acids in critically ill patients remains subject of
extensive research over the last decade, 22 amino acid profile investigated in children with severe
sepsis(SS) or severe trauma with systemic inflammatory response syndrome (SIRS)during the
early phase of stress compared with their corresponding levels in normal children serum. Also we
tried to consider the direction of this mobility (upward, downward) and to correlate with clinical
parameters, as expressed by the severity of disease or inflammatory markers (CRP).
Materials-Methods: The study included thirty-five critically ill patients aged 18years, of which
15 met the criteria for severe sepsis and 20 criteria for SIRS.These patients were compared with
27 healthy children served as controls. Serum samples from patients were collected in the first
24-hour introduction to the intensive care unit
Results: The metabolic spectrum of amino acids significantly altered in patients with sepsis.
Methionine levels in patients plasma were significantly lower than in healthy children (Post hoc
analyses SS vs. H, SIRS vs. H: p <0.001). Taurine was significantly higher in PICU patients than
in healthy children (Post hoc analyses SS vs. H, SIRS vs. H: p <0.004). In SS or SIRS patients,
negative correlations were recorded between amino acid levels and severity of disease markers (p
<0,05); Glutamine was negatively correlated with not only APACHE II but also with CRP (p
<0,05).
Conclusions: mino acids show significant variations depending on the severity of the disease
and the inflammatory response to stress. Acute stress dietary interventions with mixtures of ami-
no acids in ICU patients cannot be correctly predicted and can negatively influence metabolism.


()
Theonymfi Tavladaki
,
Anna Maria Spanaki (1).
George Briassoulis (Systemic Inflammatory Response Syndrome, SIRS) (severesepsis/septic-
Paediatric Intensive Care shock, SS) .
Unit (PICU) ,University
Hospital of Crete , ,
,
Helen Dimitriou , (2). ,
Hematology and Oncol-

ogy Laboratory, University
of Crete, Medical School
(3-5)
(6-8).
EvaggelosPapakonstantinou
Neo Lab , thens (9),
(10, 11).
Olav Rooyackers et all
o - (turnover) -

.
, sirs

236

(Energy Expenditure),
,
(9).

(12). ,
(
), ( ), .
22

.
(, ) ,
(CRP).



35
(18 ) 2012
2014 (
IRB). SIRS
SS , SIRS
. 24
.
(Ctl).


(Hitachi Ami-
noacidanalyzerL 8900)

.
135C. 570 440 nm
(570/440).

. 300 l
30 l AEC 35% SSA Ep-
pendorf. o , 30 min
(11.000x g 10 ) . 0.2
m. 140 140 1
(-21) (Vortex).
, 3 .


SD.
3 ANOVA
(SS, SIRS, Ctl) post hoc
. p 0,05
. Microsoft Excel SPSS v20.


.
SS (10 5) SIRS
(1 19) (p<0,001). (SS 4/15, 26%, SIRS
1/20, 5%, p<0,01). SS
SIRS (p<0,05),
237

.
PELOD, APACHE II ,
(TISS) ( 1).
2 3

1:

SIRS P value

N=27 N=15 N=20

() 103 9,84,9 157,5 0,143

Apache II - 11,55 22,38,8 0,000

PELOD - 9,211,7 3230 0,011

TISS 28 - 42,97,5 42,36,7 0,833

7(25,9%) 10(66,7%) 1(5%) 0.000

20(74,1%) 5(33,3%) 19(95%)

11(73,3%) 19(95%) 0,008

4(26,7%) 1(5%)

0 2(13,3%) 1(5%) 0,042

1 3(20%) 1(5%)

2 8(53,3%) 6(30%)

3 2(13,3%) 12(60%)

0 1(6,7%) 0(0%) 0,024

1 2(13,3%) 7(35%)

2 2(13,3%) 9(45%)

3 5(33,3%) 4(20%)

4 3(20%) 0(0%)

6 3(20%) 0(0%)


9,27 38,945,9 0,009
()
, sirs

238

. , , , , , ,
(p<0,005), , , (p<0,002), , (p<0,02),
(p=0,05)
(p<0,0001) ( 1).
(p=0,004)

2: control, SIRS, sepsis


SIRS P value
mol/L N=27 N=15 N=20

159,3856,53 136,8949,59 168,1472,13 0,292

139,1165,09 138,8448,65 120,7655,69 0,672

125,6131,38 118,7334,89 113,6041,25 0,503

48,3424,42 73,5220,68 62,8833,69 0,006

11,0010,66 7,785,96 103,34 0,289

45,5720,11 50,3116,87 54,0024,74 0,486

152,4259,98 131,4747,30 112,8040,29 0,115

35,5316,67 37,2314,30 32,7814,76 0,775

62,5031,83 54,9422,17 54,9314,45 0,572

65,6912,45 68,6817,63 76,6523,04 0,215

189,9595,67 96,7378,73 157,7799,50 0,005

19,319,14 16,317,23 16,828,26 0,459

11,054,71 9,024,50 8,302,84 0,152

244,95112,48 132,0784,72 169,08101,39 0,002

90,0721,00 86,1741,37 83,2926,14 0,813

34,327,40 33,5816,38 32,599,77 0,921

125,7750,95 154,4052,55 144,2586,87 0,274

70,4322,66 48,5411,37 54,2623,61 0,018

15,034,44 9,243,65 11,484,00 0,000

36,6911,35 30,8710,70 42,029,25 0,031

49,7324,74 34,1816,90 42,6922,37 0,072

236,7355,35 264,1843,46 227,7337,07 0,093


239

1: . -
(Post hoc analyses SS vs. H, SIRS vs. H: p<0.001)

( 2). , ,
, (p=0,03) .
SS SIRS. ,
SS/SIRS (post hoc: p=0,05,p=0,004, ) SIRS
SS (post hoc: p=0,05). ,
3 (p=0,514).
,

2: .
(Post hoc analyses SS vs. H, SIRS vs. H: p<0.004)
, sirs

240

,
( 3).

3: .

(p<0,05). APACHE II CRP (p<0,05)



,

24 . ,

( - CRP).

,
,
.


. ,

(SIRS) ,
- - .

SS/SIRS.
11 (13).

(1).

.
241

, (14,15)
, 1
. ,
(ATP) .
Chiarla (7), Paauw - Davis (16), Boelens (17)
Mechteld A. R. Vermeulen et al (18) 2014
,
,
.
,
.
(19, 20)
(35-50% vs. 10-20%) (21).

.

. SIRS SS
,
(22).

, , ,
,
/SIRS.

(23), .
Tomoya Hirose et al (9) S- (SAM)
.
Alexander Semmleret al (24)
, SAM .
SAM ATP (25). (9)
SAM
ATP
.
SAM,
.
, SS,
. ,
(10). ,
, ,

mtROS (26).
, (10, 11, 27, 28)
, (29),
.
.

- (30).


, ,
(31, 32). Bertolini et al (33)

(34, 35).

. -
, sirs

242

, -
, (HSPs).
in vivo in vitro
(HSP-72), mRNA
.
HSP-70

, (36).
,
,
24.

.

.


(37).


(
)
(),
: . .


1. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition
become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001 Aug
22;286(8):94453.
2. Dhaliwal R, Heyland DK. Nutrition and infection in the intensive care unit: what does the
evidence show? Curr Opin Crit Care. 2005 Oct;11(5):4617.
3. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus
late parenteral nutrition in critically ill adults. N Engl J Med. 2011 Aug 11;365(6):50617.
4. Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, et al. Optimisation
of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised
controlled clinical trial. Lancet. 2013 Feb 2;381(9864):38593.
5. Weijs PJM, Wischmeyer PE. Optimizing energy and protein balance in the ICU. Curr Opin
Clin Nutr Metab Care. 2013 Mar;16(2):194201.
6. Askanazi J, Furst P, Michelsen CB, Elwyn DH, Vinnars E, Gump FE, et al. Muscle and
plasma amino acids after injury: hypocaloric glucose vs. amino acid infusion. Ann Surg. 1980
Apr;191(4):46572.
7. Chiarla C, Giovannini I, Siegel JH, Boldrini G, Castagneto M. The relationship between
plasma taurine and other amino acid levels in human sepsis. J Nutr. 2000 Sep;130(9):22227.
8. Vente JP, von Meyenfeldt MF, van Eijk HM, van Berlo CL, Gouma DJ, van der Linden CJ,
et al. Plasma-amino acid profiles in sepsis and stress. Ann Surg. 1989 Jan;209(1):5762.
9. Hirose T, Shimizu K, Ogura H, Tasaki O, Hamasaki T, Yamano S, et al. Altered balance of
the aminogram in patients with sepsis - the relation to mortality. Clin Nutr Edinb Scotl. 2014
Feb;33(1):17982.
10. Druml W, Heinzel G, Kleinberger G. Amino acid kinetics in patients with sepsis. Am J Clin
Nutr. 2001 May;73(5):90813.
11. De Bandt J-P, Cynober L. Therapeutic use of branched-chain amino acids in burn, trauma,
and sepsis. J Nutr. 2006 Jan;136(1 Suppl):308S 13S.
12. Wang H, McNeil YR, Yeo TW, Anstey NM. Simultaneous determination of multiple amino
acids in plasma in critical illness by high performance liquid chromatography with ultraviolet and
243

fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Dec 1;940:538.
13. Tomiyasu M, Aida N, Watanabe Y, Mori K, Endo K, Kusakiri K, et al. Monitoring the brain
metabolites of children with acute encephalopathy caused by the H1N1 virus responsible for the
2009 influenza pandemic: a quantitative in vivo 1H MR spectroscopy study. Magn Reson Imag-
ing. 2012 Dec;30(10):152733.
14. Schaffer SW, Jong CJ, Ito T, Azuma J. Effect of taurine on ischemia-reperfusion injury.
Amino Acids. 2014 Jan;46(1):2130.
15. Marcinkiewicz J, Kontny E. Taurine and inflammatory diseases. Amino Acids. 2014
Jan;46(1):720.
16. Paauw JD, Davis AT. Taurine concentrations in serum of critically injured patients and age-
and sex-matched healthy control subjects. Am J Clin Nutr. 1990 Oct;52(4):65760.
17. Boelens PG, Houdijk APJ, de Thouars HN, Teerlink T, van Engeland MIA, Haarman
HJTM, et al. Plasma taurine concentrations increase after enteral glutamine supplementation in
trauma patients and stressed rats. Am J Clin Nutr. 2003 Jan;77(1):2506.
18. Vermeulen MAR, van Stijn MFM, Visser M, Lemmens SMP, Houdijk APJ, van Leeuwen
PAM, et al. Taurine Concentrations Decrease in Critically Ill Patients With Shock Given Enteral
Nutrition. JPEN J Parenter Enteral Nutr. 2015 Jan 13;
19. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiol-
ogy of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of
care. Crit Care Med. 2001 Jul;29(7):130310.
20. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epi-
demiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003
Mar 1;167(5):695701.
21. Wheeler DS, Wong HR, Zingarelli B. Pediatric Sepsis - Part I: Children are not small
adults!. Open Inflamm J. 2011 Oct 7;4:415.
22. Su L, Li H, Xie A, Liu D, Rao W, Lan L, et al. Dynamic changes in amino Acid concentra-
tion profiles in patients with sepsis. PloS One. 2015;10(4):e0121933.
23. Sax HC, Hasselgren PO, Talamini MA, Edwards LL, Fischer JE. Amino acid uptake in iso-
lated, perfused liver: effect of trauma and sepsis. J Surg Res. 1988 Jul;45(1):505.
24. Semmler A, Smulders Y, Struys E, Smith D, Moskau S, Blom H, et al. Methionine metabo-
lism in an animal model of sepsis. Clin Chem Lab Med CCLM FESCC. 2008;46(10):1398402.
25. Dever JT, Elfarra AA. The biochemical and toxicological significance of hypermethionemia:
new insights and clinical relevance. Expert Opin Drug Metab Toxicol. 2010 Nov;6(11):1333
46.
26. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial
DAMPs cause inflammatory responses to injury. Nature. 2010 Mar 4;464(7285):1047.
27. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for
sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/
SCCM Consensus Conference Committee. American College of Chest Physicians/Society of
Critical Care Medicine. 1992. Chest. 2009 Nov;136(5 Suppl):e28.
28. Fujiwara M, Ishida Y, Nimura N, Toyama A, Kinoshita T. Postcolumn fluorometric detection
system for liquid chromatographic analysis of amino and imino acids using o-phthalaldehyde/N-
acetyl-L-cysteine reagent. Anal Biochem. 1987 Oct;166(1):728.
29. Wijnands KAP, Hoeksema MA, Meesters DM, van den Akker NMS, Molin DGM, Bried
JJ, et al. Arginase-1 deficiency regulates arginine concentrations and NOS2-mediated NO pro-
duction during endotoxemia. PloS One. 2014;9(1):e86135.
30. Wijnands KAP, Castermans TMR, Hommen MPJ, Meesters DM, Poeze M. Arginine and
citrulline and the immune response in sepsis. Nutrients. 2015 Mar;7(3):142663.
31. De Jonge WJ, Hallemeesch MM, Kwikkers KL, Ruijter JM, de Gier-de Vries C, van Roon
MA, et al. Overexpression of arginase I in enterocytes of transgenic mice elicits a selective ar-
ginine deficiency and affects skin, muscle, and lymphoid development. Am J Clin Nutr. 2002
Jul;76(1):12840.
32. Barbul A, Lazarou SA, Efron DT, Wasserkrug HL, Efron G. Arginine enhances wound heal-
ing and lymphocyte immune responses in humans. Surgery. 1990 Aug;108(2):3316; discussion
3367.
, sirs

244

33. Bertolini G, Iapichino G, Radrizzani D, Facchini R, Simini B, Bruzzone P, et al. Early enter-
al immunonutrition in patients with severe sepsis: results of an interim analysis of a randomized
multicentre clinical trial. Intensive Care Med. 2003 May;29(5):83440.
34. Heyland DK, Dhaliwal R, Drover JW, Gramlich L, Dodek P, Canadian Critical Care Clini-
cal Practice Guidelines Committee. Canadian clinical practice guidelines for nutrition support
in mechanically ventilated, critically ill adult patients. JPEN J Parenter Enteral Nutr. 2003
Oct;27(5):35573.
35. Dhaliwal R, Cahill N, Lemieux M, Heyland DK. The Canadian critical care nutrition guide-
lines in 2013: an update on current recommendations and implementation strategies. Nutr Clin
Pract Off Publ Am Soc Parenter Enter Nutr. 2014 Feb;29(1):2943.
36. Jordan I, Balaguer M, Esteban ME, Cambra FJ, Felipe A, Hernndez L, et al. Glutamine
effects on heat shock protein 70 and interleukines 6 and 10: Randomized trial of glutamine
supplementation versus standard parenteral nutrition in critically ill children. Clin Nutr Edinb
Scotl. 2015 Feb 7;
37. Briassoulis G. Are early parenteral nutrition and intensive insulin therapy what critically ill
children need?*. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit
Care Soc. 2014 May;15(4):3712.
245

246

- A

. 196,
A, 11521
e-mail: ekornarou@esdy.

. edu.gr
. 2132010383,
2132010385


, , ,


: ,
.
: H
.
: , , 96
,
, 5/2013 12/2013.
SPSS.
: 70 (72,9%) .
77,9% 40 . 60%
9 . 61,4% 90%
. ,
, , , /
, . (78,6%)
. H
.
:

,
- .

, .

: ,





ORIGINAL ARTICLES

247

Correspondence
Kornarou Eleni
Networks of primary care and wel-
lexandras Av. 196, Ath-
ens, 11521
e-mail: ekornarou@esdy.
fare for deaf primary school children.
edu.gr
. +302132010383, Parents satisfaction
+302132010385

Bredaki Maria, Ktena Danai, Barbouni Anastasia, Kornarou Eleni

Abstract
Background: Deafness is a particularly difficult situation for children, as it affects their whole
life.
Objective: Our objective was to assess the effectiveness of care and welfare networks, that are
currently available to primary school children facing hearing problems and to evaluate the par-
ents satisfaction from the use of these networks.
Material and Methods: We conducted our research, using anonymous questionnaires addressed
to 96 parents of children with severe hearing problems or deafness. The children were chosen
from two primary schools in Attica, while attending there (5/2013- 12/2013). SPSS was used
for data analysis.
Results: 70 parents took part in the research (72.9%). 77.9% were mothers with mean age 40
years. 60% of the children with hearing problems were boys, with a mean age of 9 years. 61.4%
of the children used hearing aid and 90% attended special courses. Parents were satisfied from
informational campaignes, financial aid and emotional support from school, their other chil-
dren/their partner, their family and deaf adults. School was found to be the most supporting
formal care network (78.6%). Parents satisfaction from social services and insurance networks
was inadequate.
Conclusions: The parents degree of satisfaction is directly dependent from the age when the
childs hearing problem was tracked and from the parents educational level; regardless of wheth-
er the children attended special courses (except for speech therapy) or not. More effective social
support from non-official care networks and immediate vocational rehabilitation during adult-
hood from official care networks were considered necessary.

Keywords: deaf children, care-welfare networks


,
(1). ,
, ,

, , ,
Bredaki Maria , -
Ktena Danai (2,3).
Kornarou Eleni ,
National School of Public ,
Health, Department of , -
Epidemiology and Medi- (4,5,6).
cal Statistics , , ,
(7).
Barbouni Anastasia
National School of Public
,
Health, Department of , (4,8,9,10).
Public Health

248




.
, , ,
, ,
, , , .


,
,
96 ,
.
,
.
2013 2013.
, ,
1 5,
/ /.

:
1. , , ,
, , , , .
2. / (, ,
).
3. ,
, ,
.
4. , , -
, .
5.
.
6. , -
, , .



70 - (72,9%).
77,9% 22,1% .
40,75 , 7,14 .
30 56 .
66,7% , 21,7% , 5,8% 5,8%
.
52,9% , 24,3% , 18,6% 4,3% .
55,7% , 18,6% ,
15,7% 10% (, ).
, 48,6% , 32,9% , 12,9%
1,4% . ( 1)
, 60,0% 40,0% .
, 49,3% , 33,3%
17,5% .
61,4% , 35,7% 2,9%
( 2).
249

1: -

(%)

53 77,9

70 40,8

46 66,7

37 52,9

39 55,7

34 48,6

23 32,9

2:

(%)

42 60,0

1. 31 49,2

2. 21 33,3

1. 43 61,4

2. 25 35,7

25 , 22
3 .
15,3 15 .
0 48 .
1,3 1,2 .
0 2 .
9,15 3,23
. 4 15. ,
14,93
19,59 . 96 .
, 17,43
20,58 . ,
33,12
22,32 . 4 72 .

& . ,
15,7%
.

250

, 91,3% , 40,6%
, 23,2% , 11,6% 1,4%
. ( 3)

3:



% %

6 8,7% 63 91,3%

41 59,4% 28 40,6%

53 76,8% 16 23,2%

61 88,4% 8 11,6%

68 98,6% 1 1,4%

, 34,3% . 58,3%

, 20,8%
, 12,5%
8,3% .
90,0% . 65,1%
,
, 3,2% , 15,9%
15,9% .


- ,
.
.
: 1= , 2= , 3= , 4= , 5=
.

.
,
& , , ,
.
. ( 4)

/
. .
, ,
,
. ( 4)

, , .
,
,
. ,
. ( 4)
251

4: * ,

/ N N N

61 3,34 50 3,88 50 3,96

64 1,34 37 2,78 55 1,38


(.. ) 61 4,08 52 3,42 50 4,58

55 3,91 50 3,40 46 4,28

&
54 2,57 39 3,15 43 2,63

47 3,09 38 3,61 38 3,24

/ 50 2,12 48 1,58 46 1,78

33 1,79 23 2,22 28 1,43


(.. -) 51 2,57 46 2,20 48 1,90

35 2,54 28 3,21 30 2,67


51 2,80 39 3,44 46 2,48
(. -)

* : 1= , 2= , 3= , 4= , 5=

,
.
( 5)

5: *
,
.

-
, ,



()

20 31,4 7,61163


16 32,93 9,20484

.
18 29,66 5,73944

* : 1= , 2= , 3= , 4= ,
5=

252

78,6%
, 8,6% & ,
77,1% , 2,9% 2,9% . ( 6)

6:
;

(%)

55 78,6

6 8,6

5 7,1

2 2,9

2 2,9

70 100,0

57,1% , /
- , , 27,1%
, 7,1% , 5,7% 2,9%
. ( 7)

7:
;

(%)

/ - 40 57,1

- 5 7,1

- / 19 27,1

4 5,7

2 2,9

70 100,0

,
,
,
.

, p=0.06,
p=0.004 p=0.015.
, .
253


(p=0.111),
(p=0.36) (p=0,49).
(p=0.02)
(p=0.02) (p=0.01),
(p=0.114).
.

-
(p=0.64), (p=0.48)
(p=0,54 ).

(p=0.49),
(p=0.609) (p=0.54).

-
.
57,6%
-
, 68,2%
,
18,6% ( ,
, ,
, ,
).
, 60,7% -
-


.
10% , .



&
. ,
, . , -
, , -
, ,
,
.


, , /
.

, .


.

, , .

254


, &
, , .

/ - , , ,
.


.
, ( & )
.
,
.
(1999),
( - ) ( - ),
Hightower
Cowen (1984). 18 (items) ,
.
,
, .


90%
: 65,1% ,
, 3,2% , 15,9%
15,1% .
,

, , /
. ,
& ,
.
.

,
. .
, ,
,
.

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

.


1. , , , -
.. , .
255

,
.
2. ,
,
. -.
3.
, -
.
4. , -
, (, , ..)

.

1. . (1998)
. :
2. Bat-ChavaY (2000) Diversity of deaf identities. American Annals of the Deaf 145:420-428.
3. Northern J. L., & Downs, M. P. (1978). Hearing in children (2nd Ed.). Baltimore: Williams
& Wilkins.
4. Clymer E. (1995). The psychology of deafness: Enhancing self concept in the deaf and hear-
ing impraired. Family Therapy, 22, 113-120.
5. Jambor E., Elliott M. (2005). Self-esteem and Coping Strategies among Deaf Students, jour-
nal of Deaf Studiesand Deaf Education, 10, 63-81.
6. Triantis H.,C. (1996). The psychological measurement of cultural syndromes. American Psy-
chologist, 51, 407-413.
7. Schlesinger H.S. (2000). A developmental model applied to problems of deafness. Journal of
Deaf Studies and Deaf Education, 5 (4), 349-361.
8. Emerton R. G. (1996). Marginality, biculturalism, and social identity of deaf people. In. I.
Parasnis (Ed)., Cultural and language diversity and the deaf experience (pp. 136-145). Cam-
bridge: CambridgeUniversityPress.
9. . (2003),
, .
10. . . (2013). ,
http://prosvasi.uoa.gr

256

- A


-
,

deferasirox
,
e-mail: mmoschov@med.
uoa.gr
. 2107452132

, , , , -
, , ,


:
.
,
,
.
: def-
erasirox, .
: 252 . 53 -
Deferasirox .

- .
,
. deferasirox 8 (SD:4,6.
:0.4-19.2).
: , ,
.
-10,8 mg/L, (p=0,02), -92,8
mg/L (p<0,001).
-82 mg/L (p<0,001).
.

deferasirox.
: 1) . 2) deferasirox
.
3) .

: , , , , -
,
-
,

,


-
,

ORIGINAL ARTICLES

257

Correspondence
Moschovi Maria
relapse and effective prevention
Aghia Sofia Childrens
Hospital Hematology-
Oncology Unit, First
of complications of secondary he-
Department of Pediatrics,
University of Athens, mosiderosis with iron chelation with
Aghia Sofia Childrens
Hospital, Athens
e-mail: mmoschov@med. deferasirox in childhood malignan-
uoa.gr
. +302107452132
cies
icaela Nicolaou, Yiouli P. Ktena, Archontis Zampogiannis, Anastasia Athanasiadou, Spiros Vlaho-
poulos, George Lambrou, Maria Adamaki, Maria Moschovi

Summary
Introduction: Secondary iron overload often occurs in childhood malignancies, due to the mul-
tiple blood transfusions during therapy. Iron overload causes adverse effects but the iron mobi-
lization induced during chelation may cause a recurrence of neoplastic desease, as it is used to
tumor cell proliferation.
Aim of this study is to present the effectiveness and safety of deferasirox, in this group of patients.
Method: 53 out of 252 children with malignancy in remission and secondary hemosiderosis
received Deferasirox. MRI with special software was performed for the evaluation of liver and
cardiac iron overload, as well as opthalmological-audiological testing prior to the initiation of
deferasirox. Monitoring of ferritin and biochemical markers for kidney and liver function was
performed before initiation of deferasirox and during therapy. Deferasirox was administered for
an average of 6 months (SD:4.6 range: 0.4 to19.2).
Results: There was no recurrence of the neoplastic disease. The average monthly metabolic rate
of ferritin levels was -10.8 mg/L before the initiation of treatment (p=0.02), and -92.8 mg/L
during therapy with deferasirox (p<0.001). The difference in the monthly metabolic rate of
ferritin levels before and after the initiation of therapy was -82 mg/L (p<0.001). Two children
presented with skin rash, one with gastrointestinal disorders and one with fully reversible acute
renal failure. Patients continued to have follow-up for three more years.
Conclusion: 1) There was no recurrence of the neoplastic disease. 2) Deferasirox was effective in
reducing the iron load. 3) Adverse events were mild and reversible.
icaela Nicolaou
Yiouli P. Ktena
Keywrds: secondary hemosiderosis, iron chelation, Deferasirox, complications, relapse, child-
Archontis Zampogiannis hood malignancy
Anastasia Athanasiadou
Spiros Vlahopoulos Acknowledgements
George Lambrou
The authors express their acknowledgements to the children and their parents who agreed to partici-
Maria Adamaki
Maria Moschovi
pate in this study.
Hematology-Oncology There was not any funding for the use of Deferasirox in this study.
Unit, First Department
of Pediatrics, University
of Athens, Aghia Sofia
-
Childrens Hospital

(1).

258

.
,

.
,

.
Per Os Deferasirox.
,
,
.
.

, 1)
, 2)
3)

(2, 3).

Desferasirox, Desferasirox, -

.

-

252
, 53
.
deferasirox. : ()
, ()
, ()
, () [ > 2500mg/L
(MRI 2 )]
6

.
,
.
.
20 mg/kg/ 30 mg/kg/
,
3 .
.
.


, , defera-
sirox. , ,
SGOT SGPT, - (-GT), (ALP),
. : : 10 -150 mg/L, : 10-35
mg/dL, : 0,2-1,0 mg/dL, SGPT: 10-60 U/L, SGOT: 5-45 U/L, -GT: 2-50 U/L,
ALP: 60-240 U/L, (TB) <1,0 mg/dL (DB) <0,3 mg/
dL. 8 ,
4 .
259


MRI (RI 2 ) .
, ,
(4). ,
, ,
.
-

.


Stata 11 (StataCorp., College Sta-
tion, TX).
. ,


. ,


deferasirox.

, 252 1,3-21,3 9,3 , (123 , 127 )


.
: 50%, 31%, 19%.
1079 mg/L (: 3-11.500).
138 (55%) 1,3- 21,3 8,6 , (72 , 66
) ( :1906mg/L, :166-11500mg/L),
: 49%, 32%,
19%. 53 (53/138, 38%)

.
, MRI
2 1.

.

2 (>22 ms) / (55% 74%)
MRI / .
deferasirox,
, 26
(SD=17. : 2-45). deferasirox 20 mg/kg/
30 mg/kg/. 6 (SD=4.6. , 0,4
- 19,2).
. 38 mg/dL (SD=17. , 10 86)
0,62 mg/dL (SD = 0,11. , 0,43 1,03).
(3 35 45 mg/dL, 1 86 mg/dL),
,
(clearance) .
, AST 45 U/L (SD=32. , 12-
130), ALT = 61 U/L (SD=61. , 17-203), A =
274 U/L (SD=98. , 133-411), -GT =48 U/L (SD=98. , 3-369).
0,4 mg/dL (SD=0,17. , 0,2 - 1,2).
, : 2 (2/53)

260


deferasirox
. (1/53)
( ) ,
.
(1/53), (76 mg/dL)
(1,94 mg/dL), 4,8 deferasirox 20 mg/kg/d ( 314 mg/L
).
: 1100 mg/dL 34 mg/dL,
1,0 mg/dL AST 20 U/L, ALT 19 U/L, -GT13 U/L, ALP 411 U/L, 0,8 mg/
dL. deferasirox , ,
49 mg/dL 0,83 mg/
dL.
deferasirox,
( ).
,
. 4
deferasirox 20 mg/kg/d.
, de-
ferasirox, .
, 51 deferasirox 7,0
(SD=4,3. , 2,4 - 18,2). 2
.
2450 950 mg/L, .
385 mg/L, 24 .
51 ,
1901 mg/L (SD:833. :1100-3900)
deferasirox 1517 mg/L (SD:880. :687-3500).
deferasirox 7 (SD:4,3. :2,4-18,2).
deferasirox 500- 600 mg/L
.
, 18 ,
, 3.500 1.550 mg/L.
deferasirox, 606 mg/L (SD=394
mg/L. , 270-1550). -10,8
mg/L [95% CI), 19,8 1,8. = 0,02], -93,8 mg/L
deferasirox (95% CI, 118,1 69,1. <0,001).

-82 mg/L (95% CI, 111,6 53.9 <0,001).
,

.
: () .
,
1.000 mg/L () ,
,
(5).
MRI.
2800
mg/L. 4,4 deferasirox,
, 547
mg/L.
, 2900 mg/L. 5,8
728 mg/L.
MRI 1430
261

1:

, n 252
138 55%
53 38%

- 7:6

,
51% ,
, ,

()

- ,
49%

(SD), 11.04 (3.99)

2.37-16.31

(SD), mg/L 1541 (858)

687-3500

, n(%) 53

16/53

23/53

14/53

RI T2 (SD), 5.8 (2.0)


>19.1, ms

3.8-9.4

, 50
mmoL/g 205 (81)
(SD), <36

90-350

0/53

RI T2 (SD),
34.1 (5.8)
>22, ms

25.6-43

EF, % (SD) 64 (5.3)

55-71

262

mg/L. 18,2 deferasirox, 219 mg/L


.

11,6 (SD:10. :0.1-30).
4 8 .
, ( ) : 400 mg/L
(SD:257. :65-930), 34 mg/dL, 0,7 mg/dL, SGOT 42 U/L, SGPT
44 U/L, -GT 51 U/L, ALP 220 U/L, 0,5 mg/dL.

deferasirox.
.
.



.

, .
,
.
,
, (6,7).
, .
,
. ,

Deferasirox.
,
, ,
(8-12). ,
,
.

.
.
, deferasirox
.

.
T Deferasirox ,
,
.
,
. Deleas E. T. et al,
Deferasirox,
(13).
,

,
.
, ,
.
.


263

. ,
(3,14).
Defera-
sirox . Ohysashiki et. Al., Deferasirox

Hann HW et al.

(15,16). Jeon SR et al.
Deferasirox (17).

.
,
.
,
.
, .
Deferasirox . , -

,
, .

, /

. ,
,
.
deferasirox ,

.
.


.

.

1. Ruccione, K.S., Midambi K, Sposto R et al., Association of projected transfusional iron bur-
den with treatment intensity in childhood cancer survivors. Pediatr Blood Cancer, 2012. 59(4):
p. 697-702.
2. Buss, J.L., F.M. Torti, and S.V. Torti, The role of iron chelation in cancer therapy. Curr Med
Chem, 2003. 10(12): p. 1021-34.
3. Chueh, H.W., Sung KW, Lee SH, Yoo KH, Koo HH, Kim JY, et al., Iron chelation treatment
with deferasirox prior to high-dose chemotherapy and autologous stem cell transplantation may
reduce the risk of hepatic veno-occlusive disease in children with high-risk solid tumors. Pediatr
Blood Cancer, 2012. 58(3): p. 441-7.
4. Leung, A.W., Chu WC, Lam WW, Lee V, Li CK. Magnetic resonance imaging assessment
of cardiac and liver iron load in transfusion dependent patients. Pediatr Blood Cancer, 2009.
53(6): p. 1054-9.
5. Brissot, E., B.N. Savani, and M. Mohty, Management of high ferritin in long-term survivors
after hematopoietic stem cell transplantation. Semin Hematol, 2012. 49(1): p. 35-42.

264

6. Gamberini, M.R., V. De Sanctis, and G. Gilli, Hypogonadism, diabetes mellitus, hypothy-


roidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation
therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre.
Pediatr Endocrinol Rev, 2008. 6 Suppl 1: p. 158-69.
7. Wood, J.C., Noetzl L, Hyderi A, Joukar M, Coates T, Mittelman S. Predicting pituitary iron
and endocrine dysfunction. Ann N Y Acad Sci, 2010. 1202: p. 123-8.
8. Albini, A., Pennesi G, Donatelli F, Cammarota R, De FS, Noonan DM. Cardiotoxicity of
anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer
Inst, 2010. 102(1): p. 14-25.
9. Armstrong, G.T., M. Stovall, and L.L. Robison, Long-term effects of radiation exposure
among adult survivors of childhood cancer: results from the childhood cancer survivor study.
Radiat Res, 2010. 174(6): p. 840-50.
10. Ness, K.K., Saro H Armenian, Nina Kadan-Lottick, James G Gurney. Adverse effects of
treatment in childhood acute lymphoblastic leukemia: general overview and implications for
long-term cardiac health. Expert Rev Hematol, 2011. 4(2): p. 185-97.
11. Termuhlen, A.M., Tersak JM, Liu Q, Yasui Y, Stovall M, Weathers A, et al., Twenty-five
year follow-up of childhood Wilms tumor: a report from the Childhood Cancer Survivor Study.
Pediatr Blood Cancer, 2011. 57(7): p. 1210-6.
12. van der Pal H.J., van Dalen EC, Hauptmann M, Kok WE, Caron HN, van den Bos C, et
al., Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study. Arch
Intern Med, 2010. 170(14): p. 1247-55.
13. Delea, T.E., Sofrygin O, Thomas SK, et al., Cost effectiveness of once-daily oral chelation
therapy with deferasirox versus infusional deferoxamine in transfusion-dependent thalassaemia
patients: US healthcare system perspective. Pharmacoeconomics, 2007. 25(4): p. 329-42.
14. Buss, J.L., Greene BT, Turner J, Torti FM, Torti SV. Iron chelators in cancer chemotherapy.
Curr Top Med Chem, 2004. 4(15): p. 1623-35.
15. Hann, H.W., M.W. Stahlhut, and C.L. Hann, Effect of iron and desferoxamine on cell
growth and in vitro ferritin synthesis in human hepatoma cell lines. Hepatology, 1990. 11(4): p.
566-9.
16. Ohyashiki, J.H., Kobayashi C, Hamamura R, Okabe S, Tauchi T, Ohyashiki K. The oral
iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by
enhancing expression of REDD1. Cancer Sci, 2009. 100(5): p. 970-7.
17. Jeon, S.R., Lee JW, Jang PS, Chung NG, Cho B, Jeong DC. Anti-leukemic properties of
deferasirox via apoptosis in murine leukemia cell lines. Blood Res, 2015. 50(1): p. 33-9.
265

266

score A

,
11527
e-mail: alpassal@yahoo.gr;

alpassal@gmail.com
. 2132009221

, , -,


: -
PAS (Paediatric appendicitis score) - Score 4-7 -,
, 9 ,
PAS.
-: 39 4-15
PAS,
9 ( 2014 - 2015).
.
. Score

.
:

97,1% (P<0,05), 25% (P<0,05), 91,8%
(P<0,05) 50% (P<0,05).
: -
,

PAS.

: , , ,
PAS





&
,


-



&
,
ORIGINAL ARTICLES

267

Correspondence
Alexandros Passalidis
prospective evaluation new scoring
Thivon & Livadias,11527
e-mail: alpassal@yahoo.gr;
alpassal@gmail.com
system for diagnosis of acute appen-
. +302132009221
dicitis in children
Adelais Tzortzopoulou, Panagiota Giamarelou, Aikaterini Michail-Strantzia, Alexandros Passalidis

Abstract
bjective: To evaluate a new scoring system for diagnosis of acute appendicitis in children with
acute pain in the right iliac fossa, who are classified in the gray area in Paediatric appendicitis
score (PAS 4-7).
Methods: Prospective, observational study of 39 children aged 4-15 years with right iliac fossa
pain and classified in the gray zone in PAS, conducted at the pediatric emergency department
during a nine months period (May 2014 - February 2015). These children evaluated with the
new scoring system, which includes nine clinical and laboratory parameters, some of which are
not included in PAS. The ultrasound findings were disregarded. The score of each patient ac-
cording to the new score system was compared with the histological findings of his/her appendix.
Results: Of the 39 patients enrolled 35 (89,7%) had inflammatory and necrotic appendicitis, ac-
cording to the histological findings. The new scoring system was found to have sensitivity 97,1%
(P<0,05), specificity of 25% (P<0,05), positive predictive value 91.8% (P<0,05) and negative
predictive value of 50% (P<0,05).
Conclusions: Our new scoring system may contribute to the best decision of treatment in pedi-
atric patients with acute appendicitis, that initially appear with unclear clinical symptoms and
are classified in the gray area of PAS.

Keywords: Appendicitis, clinical pathway, biomarkers, Pediatric Appendicitis Score (PAS)



.
,
(1-3).

,
, .

Adelais Tzortzopoulou (Diadnostic gold standard),
Alexandros Passalidis
Second Department of : Alvarado Score Samuels Pediatric Appendicitis Score
Pediatric Surgery, Pana- (PAS) (4,5).
giotis & Aglaia Kyriakou PAS Samuel 2002
Childrens Hospital,
Journal of Pediatric Surgery.
Athens

Panagiota Giamarelou . 1.
Aikaterini Michail- score 1 3 PAS
Strantzia , 8 10 PAS
Department of Pathology, . 4 7 PAS
Panagiotis & Aglaia Kyri- follow up
akou Childrens Hospital, .
Athens
(6-8).
score

268

1: Pediatric Appendicitis Score (PAS)


Sign/Symptom Points
/

Cough/percussion/heel tapping tenderness at Right Lower Quadrant 2


,

Anorexia
1

Low-grade fever >38


1
>38

Nausea/emesis
1
/

Right Lower Quadrant tenderness on light palpation


2

Leucocytosis (>10000/mm3)
1
( >10000/mm3)

Left shift (>75% neutrophilia)


1
>75%

Migration of pain to Right Lower Quadrant


1


,

, 9 - .
,
6
,

PAS (9,10,27,28).


,
& 9
( 2014 2015).
215 , 4 15 ,
PAS. PAS
( PAS 4-7), 39 , 23 16 ,
.
, ,

.

, PAS
.
: 1. 6 , 2.
269

, 3. > 37,5, 4. Mc Burney , 5.


, 6. Rovsing , 7.
, (Face-pain scale)
, ( 10
1,
10
2), 8. (WBC) >
10.000 / CRP > 5mg/dl, 9. (NE%) > 75%.
4, 5 6 2 1 .
score 9 12. ,
score 6 ( 2)
(11-19,20-24).

2:

6 1

> 37,5, 1

Mc Burney 2

Rovsing 2


:
. > 10
1 1
. < 10
2

(WBC) > 10.000 / CRP > 5mg/dl 1

(NE%) > 75% 1

,
,

,
. ,
1-8 10
(11,25,28,30).

, ,
.
: .
, .
. .
(23,29).
score

270


39 -, 23 16
3 15 , 9 (
2014 2015).
PAS (4-7 score).
2 (5,2%) score
<6, . 37 (94,8%) score
>6, .
, 35 -
/ . , score <6 o
.
score >6 7 (18,9%),
27 (73%) 3
(8,1%). 7

1 (4,6,7).

.
ROC (Receiver Operating Characteristic curve)

100% 100%.
1.

1: ROC

/ -
- PAS
97,1%, 25%, 91,8%
50%. 1 ,
(0,75, 0,971)
(0,1).

ROC, ,
ROC.
271


,
.

, ,

PAS

(9,28,31).

1. Kelly- Quon Li, Tseng CH, Jen HC, Lee SL, Shew SB, Hospital type as a metric for racial
disparities in pediatric appendicitis. J Am Coll Surg. 2013;216(1):74-82
2. Thompson GC. Variations in the diagnosis and management of acute appendicitis at Cana-
dian pediatric emergency departments. American Academy of Pediatrics, Pediatr Emerg Care.
2012;28(10): 1099-1100
3. Joon Sung Kim, Acute Abdominal Pain in Children, Pediatr Gastroenterol Hepatol Nutr
2013, 16(4):219-224
4. Mandeville K, Pottker T, Bulloch B, Liu J, Using appendicitis scores in the pediatric ED. Am
J Emerg Med. 2011Nov;29(9):972-7
5. Escriba A , Gamell AM, Fernandez Y, Quintilla JM, Cubells CL, Prospective validation of two
systems of classification for the diagnosis of acute appendicitis, Emerg Care 2011Mar;27(3):165-
9
6. Samuel M, Pediatric Appendicitis Score, J Pediatric Surgery, 2002 Jun;37(6):877-81
7. Saucier A, Huang EY, Emeremni CA, Pershad J, Prospective evaluation of a clinical pathway
for suspected appendicitis, 2014 Jan;133(1):e88-95
8. Neff LP , Ladd MR, Becher RD, Jordanhazy RA, Gallaher JR, Pranikoff T, Computerized
tomography utilization in children with appendicitis-differences in reffering and childrens hos-
pitals. Am Surg. 2011;77(8):1061-1065
9. Kulik DM, Uleryk EM, Maquire JL, Does this child have appendicitis? A systematic re-
view of clinical prediction rules for children with acute abdominal pain. J Clin Epidemiol 2013
Jan;66(1):95-104
10. Bhangu A, Nepoqodiev D, Taylor C, Durkin N, Patel R, Accuracy of clinical coding from
1210 appendicectomies in a British district general hospital, International Journal of surgery
10(2012) 144-147
11. McCartan DP, Fleming FJ, Grace PA The management of right iliac fossa pain- is timing
everything? Surgeon 2010;8(4):211-7
12. Guller U, Rosella L, McCall J, Brugger LE, Candinas D, Negative appendectomy and per-
foration rates in patients undergoing laparoscopic surgery for suspected appendicitis, Br J Surg
2011 Apr;98(4):589-95
13. Tomlinson D, von Baeyer CL, Stinson JN, Sung L, A Systematic Review of Faces Scales for
the Self-report of Pain Intensity in Children, Pediatrics 2010 Nov;126(5):e1168-98
14. Salo M, Friman G, Stenstrom P, Ohlsson B, Arnbjornsson E, Appendicitis in children: Eval-
uation of the Pediatric Appendicitis Score in Younger and Older Childrenn, Surg Res Pract.
2014;2014:438076
15. Zakaria O, Sultan TA, Khalil TH, Wahba T, Role of clinical judgment and tissue harmonic
imaging ultrasonography in diagnosis of paediatric acute appendicitis, World J Emerg Surg 2011
Nov16;6(1):39
16. Bundy DG, Byerley JS, Liles EA, Perrin EM, Katznelson J, Rice HE, Does this child have
appendicitis?, JAMA 2007 Jul25;298(4):438-51
17. Sack U, Biereder B, Elouahidi T, Bauer K, Keller T, Trobs RB, Diagnostic value of blood
inflammatory markers for detection of acute appendicitis in children, BMC Surg. 2006;6:15
18. Kwan KY, Nager AL, Diagnosing pediatric appendicitis: usefulness of laboratory markers,
Am J Emerg Med. 2010 Nov;28(9):1009-15
score

272

19. Kharbanda AB, Cosme Y, Liu K, Spitalnik SL, Dayan PS, Discriminative Accuracy of Novel
and Tranditional Biomarkers in Children with suspected appendicitis adjusted for duration of
abdominal pain, Acad Emerg Med. 2011 Jun;18(6):567-574
20. C.-W. Yu, L.-I. Juan, Wu MH, Shen CJ, Wu JY, Lee CC, Systematic review and meta- anal-
ysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for
suspected acute appendicitis, British Journal of Surgery 2013;100:322-329
21. .. , , 4 , 2006 .
22. Lynn S. Bickley, BATES Guide to Physical Examination and History Taking, Tenth Edi-
tion 2009, Lippincott Wiliams & Wilkins
23. Otake S, Suzuki N, Takahashi A, Toki F, Nishi A, Yamamoto H et al, Histological analysis
of appendices remoned during internal appendectomy after conservative management of pedi-
atric patients with acute appendicitis with an inflammatory mass or abscess, Surg Today, 2014
Aug;44(8):1400-5
24. Lobo-Machin I, Delgado- Plasencia L, Hernandez- Gonzalez I, Brito-Garcia A, Burillo-Putze
G, Bravo-Gutierrez A et al, Appendiceal diverticulitis and acute appendicitis: differences and
similarities, Rev Esp Enferm Dig. 2014 Aug;106(7):452-8
25. Hornby ST, Shahtahmassebi G, Lynch S, Ladwa N, Stell DA, Delay to surgery does not
influence the pathological outcome of acute appendicitis, Scand J Surg. 2014 Mar;103(1):5-11
26. Schellekens DH, Hulsewe KW, van Acker BA, van Bijnen AA, de Jaegere TM, Sastrowijoto
SH et al, Evaluation of the diagnostic accuracy of plasma markers for early diagnosis in patients
with suspected acute appendicitis, Acad Emerg Med. 2013 Jul;20(7):703-10
27. Tsioplis C, Brockschmidt C, Sander S, Henne-Bruns D, Kornmann M, Factors influ-
encing the course of acute appendicitis in adults and children, Langenbecks Arch Surg. 2013
Aug;398(6):857-67
28. Sadot E, Wasserberg N, Shapiro R, Keidar A, Oberman B, Sadetzki S, Acute appendicitis
in the twenty- first century: should we modify the management protocol?, J Gastrointest Surg.
2013 Aug;17(8):1462-70
29. Farach SM, Danielson PD, Walford NE, Harmel RP Jr, Chandler NM, Operative findings
Are a Better Predictor of Resource Utilization in Pediatric Appendicitis, J Pediatr Surg. 2015
Sep;50(9):1574-8
30. F.Bruder Stapleton, Robert C. Tasker, Fluids and electrolytes. In: F.Bruder Stapleton, Rob-
ert C. Tasker et al, Oxford American Handbook of Pediatrics, New York: Oxford University
Press 2009
31. Schuh S, Man C, Cheng A, Murphy A, Mohanta A, Moineddin R et al, Predictors of
non- diagnostic ultrasound scanning in children with suspected appendicitis, J. Pediatr.
2011;158(1):112-118
273
www.e-child.gr

You might also like