1Volume 75 Number 3-4 July-December 2012Volume 75 Number 3-4 July-December 2012

75 3-4 I- 2012 75 3-4 I- 2012

www.e-child.grwww.e-child.gr

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3Trimonthly publication of the Greek Paediatric Society

PaediatrikiVolume 75 Number 3-4 July-December 2012

PresidentA. Constantopoulos

Editorial boardDirectorG. S. Varlamis

MembersS. AndronikouE. GalanakisA. EvangeliouL. ThomaidouM. KanariouA. KapogiannisS. Kitsiou-TzeliE. MantadakisP. Panagiotopoulou-GartaganiA. PapadopoulouV. PapaevagelouA. PapathanassiouA. Siamopoulou-MavridouA. Syrigou-Papavasiliou

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Annual subscriptionAll foreign countries: US$50

CONTENTS

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EDITORIALG.S.Varlamis

SPECIAL ARTICLEGreek Neonatal Society: Guidelines for management of hyperbilirubinemia in in-fants gestational age 35 weeks or moreD. Konstantinou, A. Varvarigou, A. Daskalaki, E. Diamanti

REVIEW ARTICLESFood allergy in infancy and childhood: diagnosis, management and future ap-proachesA. Mavroudi, I. Xinias

Food protein induced enterocolitis syndrome: an unusual type of food allergy Evangelia Stefanaki, Stavroula Giavi, Savvas Savvatianos, Nikolaos Douladiris, Emman-ouel Manousakis, Nicolaos Papadopoulos

Attention deficit hyperactivity disorder: a review of the essential factsAggeliki Skardoutsou

Genetics in Diabetes Mellitus type 1Panagiota Triantafyllou, Charikleia Chatzisevastou

ORIGINAL ARTICLESDysmetabolic syndrome manifestation is not related with therapy stages in acute lymphoblastic leukemia of childhoodE. Koultouki, G. Trimis, G. Lambrou, M. Tsotra, N. Tourkantoni, K. Karamolegou, M. Ad-amaki, J. Papassotiriou, G. Chrousos, F. Tzortzatou-Stathopoulou, M. Moschovi

Evaluation of potential benefit of universal rotavirus vaccination program in GreeceV. Syriopoulou, D. Kafetzis, M. Theodoridou, G. Syrogiannopoulos, St. Mantagos, M. Ma-vrikou, G. Trimis, A. Konstantopoulos

CASE REPORTSMolecular study in jacobsen syndrome with array cghelen Leze, Maria Tzetis, Konstantina Kosma, Areti Syrmou, Krinio Giannikou, Vasilis Oikonomakis, Elisabeth Kouvidis, Aggeliki Nika, Ioannis Kapetanakis, Emmanuel Ka-navakis, Sofia Kitsiou-Tzeli

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e-mail: grammateia@e-child.gr

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5Trimonthly publication of the Greek Paediatric Society

PaediatrikiPresidentA. Constantopoulos

Editorial boardDirectorG. S. Varlamis

MembersS. AndronikouE. GalanakisA. EvangeliouL. ThomaidouM. KanariouA. KapogiannisS. Kitsiou-TzeliE. MantadakisP. Panagiotopoulou-GartaganiA. PapadopoulouV. PapaevagelouA. PapathanassiouA. Siamopoulou-MavridouA. Syrigou-Papavasiliou

CONTENTS

116

122

Manuscript submissione-mail: grammateia@e-child.gr

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

OwnerGreek Paediatric Society15, Mpakopoulou st.GR - 15451, . PsychikoT.: +302107771140,e-mail: grammateia@e-child.gr

Annual subscriptionAll foreign countries: US$50

130

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Volume 75 Number 3-4 July-December 2012

Autochthonous malaria by Plasmodium vivax in two children from Thiva: First re-ported paediatric cases 20 years after the eradication of the disease in Greece. Polymerou, P. Korovessi, G. Amountza, G. Kampouropoulou, E. Antonopoulou, A. Peg-kou, I. Papadea

Childhood Cystic Nephroma: diagnosis and treatment (Case Presentation)V. Papadakis, A. Papanikolaou, K. Stefanaki, J. Alexandrou, M. Zeis, Sp. Antypas

Candida parapsilosis endocarditis in a premature neonate. Successful outcome with combined antifungal and surgical treatmentK. Papadopoulou-Legbelou, G. Kalavrouziotis, C. Reveliotis, K. Karachristou, M. Lithoxo-poulou, G. Varlamis, N. Nikolaidis

BOOK REVIEW The children invite us to have a dialogue.oukou M., Georgouli A.

ACKNOWLEDGMENT

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SPECIAL ARTICLE

D. Konstantinou 1

NICU, IASO Maternity Hospital, Athens, Greece

A. Varvarigou 2

Neonatal Dpt University Hospital of Patras, Patras, Greece

A. Daskalaki 3

Neonatal Dpt Attikon Hospital, Athens, Greece

E. Diamanti 4

1st Neonatal Dpt Aristotle University of Thessaloniki, Thes-saloniki, Greece

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Greek Neonatal Society: Guidelines for management of hyperbilirubinemia in infants gestational age 35 weeks or more

D. Konstantinou 1, A. Varvarigou 2, A. Daskalaki 3, E. Diamanti 4

Hyperbilirubinemia is the most common neonatal problem which requires medical intervention in order to avoid neonatal encephalopathy and/or kernicterus, both rarely seen. Since the management of hyperbilirubinemia is not evidence based, guidelines for its management differ between countries. A lack of guidelines in Greece resulted in un-necessary treatment of jaundiced babies without justification, fearing bilirubin increase and the wrong aspect that prophylactic phototherapy can improve the final outcome. In order to establish a common and logical management program for neonatal jaundice in our country, a working team of neonatologists appointed by the Greek Neonatal Soci-ety established these guidelines, based on management protocols from other countries. Thus, we expect the same management of neonatal jaundice from all pediatricians, using common guidelines and minimizing or eliminating unnecessary medical interventions. In addition we will strive to avoid the unnecessary interruption of breast feeding of jaun-diced infants.

Key words: Neonatal Jaundice, Hyperbilirubinemia, Guidelines

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CorrespodenceDimitris KonstantinouNICU IASO Maternity Hospital, Kifissias Av 37-39, 15123 Maroussi, Athens, Greecee-mail: dikoxr@otenet.gr

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1. Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Ges-tation, Subcommitee on Hyperbilirubinemia, Pediatrics 2004;114:297-316.

2. Barrington KJ, Sankaran K. Canadian pediatric society. Guidelines for detection, man-agement and prevention of hyperbilirubinemia in term and late preterm newborn in-fants, Paediatr Child Health 2007;12(Supl B): 1B-12B.

3. Kaplan M, Merlob P and Regev R. Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus. J Perinatol 2008;28:389-387.

4. National Collaborating Centre for Womens and Childrens Health, Neonatal Jaundice, National Institute for Health and Clinical Excellence, Clinical Guidelines for the NHS by NICE, May 2010.

5. Bratlid D, Nakstad B, Hansen TW. National guidelines for treatment of jaundice in the newborn. Acta Paediatr. 2011;100(4):499-505.

6. aisels MJ, Kring E. Transcutaneous bilirubinometry decreases the need for serum bilirubin measurements and saves money. Pediatrics 1997 Apr;99(4):599-601.

7. Roubatelli FF, Gourley GR LoskampN et al, Transcutaneous bilirubin measurement: a multicenter evaluation of a new device. Pediatrics 2001 Jun;107(6):1264-71.

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21

BiliCheck. 37o 28-30 1999, .

9. Maisels J and McDonagh AF, Phototherapy fon Neonatal Jaundice, N Engl J Med 2008;358:920-8.

10. Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark A, Watchko JF. Hyperbilirubine-mia in the Newborn Infant 35 Weeks Gestation: An Update with Clarifications. Pediat-rics 2009;124:1193-1198.

11. Newman TB, Liljestrand P, Jeremy RJ, Ferriero D, Wu Y, Hudes E et al, Outcomes among Newborns with Total Serum Bilirubin Levels of 25 mg per Deciliter or More, N Engl J Med 2006;354:1889-1949.

12. Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for Subsequent significant hyperbilirubinemia in healthy term and near-term newborns, Pediatrics 1999 ;103 : 6-14.

13. Varvarigou A, Fouzas S, Skylogianni E, Mantagou L, Bougioukou D, Mantagos S. Trans-cutaneous bilirubin nomogram for prediction of significant neonatal hyperbilirubinemia. Pediatrics 2009; 124: 1052-59.

14. Maisels J, Ostrea E, Touch S, Clune S, Cepeda E, Kring E et al, Evaluation of a new Transcutaneous Bilirubinometer. Pediatrics 2004; 113; 1628.

15. aisels M J. Screening and early postnatal management strategies to prevent haz-ardous hyperbilirubinemia in newborns of 35 or more weeks of gestation. Seminars in fetal & neonatal medicine 2010;15:129-135.

16. ABM Clinical protocol 22: Guidelines for management of jaundice in the breastfed-ing infant equal to or greater than 35 weeks gestation. The Academy of breastfeeding medicine protocol committee. Breastfeeding medicine 2010;5(2):87-93.

17. Ostrow JD, Pascolo L, Shapiro SM, Tiribelli C. New concepts in bilirubin encephalopa-thy. Eur J Clin Invest Review 2003 Nov;33(11):988-97.

18. Shapiro SM. Definition of the clinical spectrum of kernicterus and bilirubin induced neurologic dysfunction (BIND). J Perinatol 2005 Jan;25(1):54-59.

19. Gourley GR, Kreamer B, Cohnen M, Kosorok MR. Neonatal jauntice and diet. Arch Pediatr Adolesc Med. 1999 Feb;153(2):184-8.

20. Hulzebos CV, van Imhoff DE, Bos AF, Ahlfors CE, Verkade HJ, Dijk PH. Usefulness of the bilirubin/albumin ratio for predicting bilirubin-induced neurotoxicity in premature in-fants. Arch Dis Child Fetal Neonatal Ed. 2008 Sep;93(5):F384-F388.

21. Ahlfors CE, Amin SB, Parker AE. Unbound bilirubin predicts abnormal automated audi-tory brainstem response in a diverse newborn population. J Perinatol 2009 Apr;29(4):305-309. Epub 2009 Feb 26.

22. Gottstein R and Cooke RWI. Systematic review of iv immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed 2003;88:F6-F10.

22

Abstract

. . (..) -

A. MavroudiI. Xinias3rd Pediatric Department, Aris-totle University of Thessaloniki, Ippokratio-General Hospital of Thessaloniki

REVIEW ARTICLES

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Food allergy in infancy and childhood: diagnosis, man-agement and future approaches

A. Mavroudi, I. Xinias

Food allergy is common in childhood affecting up to 8% of children less than 3 years of age. Food induced allergic reactions are responsible for a variety of symptoms involv-ing the skin, the gastrointestinal and the respiratory tract, caused by IgE-mediated or/and non-IgE-mediated mechanisms. Allergic eosinophilic gastroenteritis is characterized by eosinophilic infiltration of the gastrointestinal tract, and most patients have multi-ple food allergies.In case of multiple sensitivities a period of strict elimination followed by careful reintroduction of foods, one after the other can help to establish foods that are to be avoided.Oral food challenges are invaluable in the appropriate diagnosis and management of patients with food allergy. Once the diagnosis of food hypersensitiv-ity is established, the only proven therapy is strict elimination of the offending allergen. Injectable epinephrine and oral antihistamines should be readily availible at all times to treat patients, who are at risk of acute severe food induced anaphylaxis. Several novel immunoterapeutic strategies are being examined as treatment modalities for IgE-medi-ated food allergy, such as humanized anti-IgE monoclonal antibody therapy, engineered allergen protein immunotherapy, peptide immunotherapy. Currently, the treatment of

23

66, 543 52, , : 2310909632 Fax: 2310992981 : 6976718209 e-mail: antigonemavrudi@gmail.com

CorrespodenceAntigoni MavroudiSpirou Loui 66 St., 543 52, Pilea, Thes-salonikiTel: +302310909632Fax: +302310992981Mob: +30 6976718209e-mail: antigonemavrudi@gmail.com

food allergy is directed to the complete avoidance of the offending food allergens and its success is depended on the correct identification of the allergens and their complete exclusion from the diet.

Key words: Food allergy, eosinophilic gastroenteritis, food challenges, anaphylaxis, children.

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30

1. Mary V. Lasley. Adverse reactions to foods. Nelson Essentials of Pediatrics, 5th ed. Phil-adelphia. Elsevier Saunders Co; 2006. p 419-421.

2. M. Thirumala Krishna, George Mavroleon, Stephen Tholgate. Food Allergy. Essentials of Allergy, United Kingdom: Martin Dunitz Ltd ;2001 p107-127.

3. S. Allan Bock, Hugh A. Sampson. Evaluation of Food Allergy. Pediatric Allergy: Principles and Practice. USA: Elseviers Health Sciences ;2003 p 478-487.

4. Ronina A. Covar, Joseph D. Spahn, Stanley J. Szefler. Special Considerations for Infants and Young Children. Pediatric Allergy: Principles and Practice. USA Elseviers Health Sci-ences; 2003 p 379-391.

5. Sampson HA, Anderson JA: Summary and recommendations: classification of gastro-intestinal manifestations due to immunologic reactions to foods in infants and young children.J Pediatr Gastroenterol Nutr 2000 ;30(Suppl): S87-S94.

6. Kelly KJ: Eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr 2000;30 (Suppl): S28-S35.

7. Takafuji S, Bischoff SC, De Weck AL, Dahinden CA. IL-3 and IL-5 prime normal human eo-sinophils to produce leukotriene C4 in response to soluble agonists. J Immunol 1991;147: 3855-3861.

8. Burks AW, James JM, Hiegel A, Wilson G, Wheeler JG Jones SM, et al. Atopic dermatitis and food hypersensitivity. J Pediatr 1998;132: 132-136.

9. Sporik R, Hill DJ, Hosking CS: Specificity of allergen skin testing in predicting prositive open food challenges to milk egg and peanut in children. Clin Exp Allergy 2000;30: 1540-1546.

10. Hill DJ, Hosking CS, Reyes-Benito MLV: Reducing the need for food allergen challeng-es in young children: comparison of in vitro with in vivo tests. Clin Exp Allergy 2001;31: 1031-1035.

11. Rance F, Juchet A, Bremont F, et al. Correlations between skin prick tests using com-mercial extracts and fresh foods, specific IgE and food challenges. Allergy 1997;52: 1031-1035.

12. Lockey RF: Adverse reactions associated with skin testing and immunotherapy. Al-lergy Proc 1995; 16:293-296.

13. Sampson HA: Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol 2001;107: 891-896.

14. Arvola T, Holmberg-Marttila D: Benefits and risks of elimination diets. Ann Med 1999; 31: 293-298.

15. Liu T, Howard RM, Mancini AJ, Weston WL, Paller AS, Drolet BA,et al. Kwashiorkor in the United States: fad diets, perceived and true milk allergy, and nutritional ignorance. Arch Dermatol .2001;137: 630-636.

16. Liacouras CA, Markowitz JE: Eosinophilic esophagitis: A subset of eosinophilic gastro-enteritis. Curr Gastroenterol Rep . 1991;1: 253-258.

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17. Bock SA, Munoz-Furlogn A, Sampson HA: Fatalities caused by anaphylactic reactions to foods. J Allergy Clin Immunol 2001;107: 191-192.

18. AAAAI Board of Directors. Anaphylaxis in schools and other child-care settings. J Al-lergy Clin Immunol.1998;102: 173-176.

19. Beyer K, Eckermann O, Hompes S, Grabenhenrich L& Worm M. Anaphylaxis in an emergency setting-elicitors, therapy and incidence of severe allergic reactions. Allergy 2012; 67: 1451-1456.

20. Sampson HA: Immunological approaches to the treatment of food allergy, Pediatr Allergy Immunol.2001;12: 91-96.

21. Nowak-Wegrzyn A, Sampson H. Future Therapies for food Allergies. J Allergy Clin Im-munol 2011; 127: 558-573.

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Abstract

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Evangelia Stefanaki1 2nd Pediatric Department, Venizelion General Hospital, HeraklionStavroula Giavi2

Savvas Savvatianos2

Nikolaos Douladiris2

Emmanouel Manousakis2

Nicolaos Papadopoulos2

Allergy Department, 2nd Pediatric Clinic, University of Athens, Childrens Hospital P & A Kyriakou

REVIEW ARTICLES

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1, 2, 2, 2, 2, 2

(food protein induced enterocolitis syn-drome-FPIES) - . , . . , FPIES. TNF- TGF- FPIES. FPIES . .

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Food protein induced enterocolitis syndrome: an unusu-al type of food allergy

Evangelia Stefanaki1, Stavroula Giavi2, Savvas Savvatianos2, Nikolaos Douladi-ris2, Emmanouel Manousakis2, Nicolaos Papadopoulos2

Food protein induced enterocolitis syndrome-FPIES-is an unusual T-cell mediated gas-trointestinal food hypersensitivity reaction. It begins in the first months of life either pro-gressively with emesis, diarrhea and failure to thrive or with acute emesis with or with-out diarrhea after first ingestion of food. Symptoms resolve after the causal protein is removed from the diet but recur with a characteristic way on re-exposure. Milk, soya and rice are the most common causes of FPIES. Imbalance in expression TNF- TGF- may be important in the pathophysiology of FPIES. Natural history of FPIES differs according to the population. Increased index of suspicion will lead to early diagnosis and treatment.

Key-words: Food allergy, enterocolitis, milk, soya, rice

33

22,71409 , : 2810210140e-mail: evangeliastefanaki@yahoo.gr

CorrespodenceStefanaki Evangelia22, Kariotaki St.,71409 Heraklion, CreteTel: +302810210140e-mail: evangeliastefanaki@yahoo.gr

FPIES = Food protein induced entero-colitis syndrome-

SPT = Skin Prick Test-

APT = Atopy Patch Test-

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TGF- = Transforming Growth Factor -

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: 60% : 80% -: 25% : -

(, )/

( 15%), (+) . ,

1-3h 5h (24%)

500.000mm3

37

(Atopy Patch Test-) 19 (5-30 ) FPIES 27. 28 33 . 5 . , . FPIES. FPIES . , , 17,28. , . 17,29.

FPIES FPIES . 18-24 30. 27 FPIES 64% 10 92% 31. FPIES 12 6 8 . FPIES 4. 0,06-0,6gr/kg , 6,32. , 3-6 gr 10-20 gr ( 100 ml ). 3 45 33. 2-3 , . 30. H FPIES 6. 20ml/kg/ . , - . . Hwang 34. 15 16 >10/ , 3 , 2 . ,

38

, . , FPIES 60% , ( )5,6,30. 3-10 . 20% 35,36. . ..., FPIES / FPIES 6 5,10. Mehr 83% FPIES . ()14. , , . ... FPIES 80% . ( ) 50% . ,

FPIES

, (>50% IV / )

+

( 1h) 0,06-0,6g/kg/kg ( 3gr 10gr) , . .

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4: FPIES

39

FPIES

FPIES , . , , . ( , , ) 30.

. 60% 25%, , 3 (...). FPIES 3 , 40% , 66% 67% (). ... FPIES , 6,10. 3 83% 80% 10 , 64% 92% 31. FPIES 1 . ... FPIES . FPIES10,30. FPIES IgE , IgE 6. IgE . FPIES. FPIES10,14. , .

. FPIES37. FPIES in vitro (p

40

40. TNF-a . Chung TGF- (Transforming Growth Factor-) 28 FPIES 41. TGF- . 1 TGF- (p

41

11. Levy Y, Danon YL. Food protein-induced enterocolitis syndrome not only due to cows milk and soy. Pediatr Allergy Immunol 2003;14:3259.

12. Monti G, Castagno E, Liguori SA, Lupica MM, Tarasco V, Viola S, et al. Food proteininduced enterocolitis syndrome by cows milk proteins passed through breast milk. J Al-lergy Clin Immun 2011 Article in press.

13. Lake AM. Food-induced eosinophilic proctocolitis. J Pediatr Gastroenterol Nutr 2000;30: 5860.

14. Mehr S, Kakakios A, Frith K, Kemp AS. Food protein-induced enterocolitis syndrome: 16-year experience. Pediatrics 2009; 123:459464.

15. Faber MR, Rieu P, Semmekrot BA, Van Krieken JH, Tolboom JJ, Draaisma JM. Allergic colitis presenting within the first hours of premature life. Acta Paediatr 2005; 94:15141515.

16. Eggertsen SC, Pereira PK. Necrotizing enterocolitis and milk protein intolerance:causes of rectal bleeding in a term infant. J Fam Pract 1989; 28:219223.

17. Masumoto K, Takahashi Y, Nakatsuji T, Arima T, Kukita J. Radiological findings in two patients with cows milk allergic enterocolitis. Asian J Surg 2004; 27:238240.

18. Jayasooriya S, Fox AT, Murch SH. Do not laparotomize food-protein-induced entero-colitis syndrome. Pediatr Emerg Care 2007; 23:173175.

19. Murray K, Christie D. Dietary protein intolerance in infants with transient methemo-globinemia and diarrhea. J Pediatr;122:902.

20. Anand RK, Appachi E. Case report of methemoglobinemia in two patients with food protein-induced enterocolitis. Clin Pediatr (Phila) 2006; 45:679682.

21. Zapatero RL, Alonso LE, Martin FE, Martinez Molero MI. Food-protein-inducedentero-colitis syndrome caused by fish. Allergol Immunopathol (Madr) 2005;33:312316.

22. Hojsak I, Kljaic-Turkalj M, Misak Z, Kolacek S. Rice protein-induced enterocolitis syn-drome. Clin Nutr 2006; 25:533536.

23. Gray HC, Foy TM, Becker BA, Knutsen AP. Rice-induced enterocolitis in an infant. TH1/TH2 cellular hypersensitivity and absent IgE reactivity. Ann Allergy Asthma Immunol 2004; 93:601605.

24. F. Bruni, D. G. Peroni, G. L. Piacentini, G. De Luca,A. L. Boner. Fruit proteins: another cause of food protein-induced enterocolitis syndrome Allergy 2008: 63: 16401646.

25. Sampson HA, Anderson JA. Summary and recommendations: classification of gas-trointestinal manifestations due to immunologic reactions to foods in infants and young children. J Pediatr Gastroenterol Nutr 2000; 30:S87S94.

26. Hwang JB, Lee SH, Kang YN, Kim SP, Suh SI, Kam S. Indexes of suspicion of typical cows milk protein-induced enterocolitis. J Korean Med Sci 2007; 22:993997.

27. Fogg MI, Brown-Whitehorn TA, Pawlowski NA, Spergel JM. Atopy patch test for the diagnosis of food protein-induced enterocolitis syndrome. Pediatr Allergy Immunol 2006; 17:351355.

28. Richards DG, Somers S, Issenman RM, Stevenson GW. Cows milk protein/soy protein allergy: gastrointestinal imaging. Radiology 1988; 167:721723.

29. McIlhenny J, Sutphen JL, Block CA. Food allergy presenting as obstruction in an in-fant. AJR Am J Roentgenol 1988; 150:373375.

42

30. Sicherer SH. Food protein-induced entercolitis syndrome: case presentations and management lessons. J Allergy Clin Immunol 2005; 115:149156.

31. Hwang JB, Sohn SM, Kim AS. Prospective follow up-oral food challenge in food pro-tein-induced enterocolitis syndrome. Arch Dis Child 2009; 94:425428.

32. Powell GK. Food protein-induced enterocolitis of infancy: differential diagnosis and management. Comp Ther 1986; 12:2837.

33. A health professionals guide to food challenges. Mofidi S, Bock SA, editors. Fairfax, Virginia, USA: The Food Allergy and Anaphylaxis Network; 2004.

34. Hwang JB, Song JY, Kang YN, Kim SP, Suh SI, Kam S, et al. The significance of gastric juice analysis for a positive challenge by a standard oral challenge test in typical cows milk protein-induced enterocolitis. J Korean Med Sci 2008; 23:251255.

35. Vanderhoof JA, Murray ND, Kaufman SS, Mack DR, Antonson DL, Corkins MR et al. Intolerance to protein hydrolysate infant formulas: an underrecognized cause of gastro-intestinal symptoms in infants. J Pediatr 1997; 131:741744.

36. Kelso JM, Sampson HA. Food protein-induced enterocolitis to casein hydrolysate for-mulas. J Allergy Clin Immunol 1993; 92:909910.

37. Powell GK, McDonald PJ, VanSickle GJ, Goldblum RM. Absorption of food protein antigen in infants with food protein-induced enterocolitis. Dig Dis Sci 1989; 34:781788.

38. VanSickle GJ, Powell GK, McDonald PJ, Goldblum RM. Milk and soy protein induced entercolitis: evidence for lymphocyte sensitization to specific food proteins. Gastroenter-ology 1985; 88:19151921.

39. Rodriguez P, Heyman M, Candalh C, Blaton MA, Bouchaud C. Tumour necrosis fac-tor-alpha induces morphological and functional alterations of intestinal HT29 cl.19A cell monolayers. Cytokine 1995; 7:441448.

40. Benlounes N, Candalh C, Matarazzo P,Dupont C, Heyman M. The time-course of milk antigen induced TNF-alpha secretion differs according to the clinical symptoms in chil-dren with cows milk allergy. J Allergy Clin Immunol 1999; 104:863869.

41. Chung HL, Hwang JB, Park JJ, Kim SG. Expression of transforming growth factor beta1, transforming growth factor type I and II receptors, and TNF-alpha in the mucosa of the small intestine in infants with food protein-induced enterocolitis syndrome. J Al-lergy Clin Immunol 2002; 109:150154.

42. McDonald PJ, Goldblum RM, VanSickle GJ, Powell GK. Food protein-induced entero-colitis: altered antibody response to ingested antigen. Pediatr Res 1984;18:751755.

43. Shek LP, Soderstrom L, Ahlstedt S, Beyer K, Sampson HA. Determination of food spe-cific IgE levels over time can predict the development of tolerance in cows milk and hens egg allergy. J Allergy Clin Immunol 2004; 114:387391.

43

44

Abstract

. , ,

Aggeliki Skardoutsou2nd Department of Pediatrics, University of Athens, Aglaia Kyri-akou Childrens Hospital, Athens, Greece

REVIEW ARTICLES

- .

.

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

: , , , , , .

Attention deficit hyperactivity disorder: a review of the essential facts

Aggeliki Skardoutsou

Attention deficit hyperactivity disorder (ADHD) is a complex disability: both genetic and environmental influences make a substantial contribution to the risk for the disor-der. Comorbidity with learning disabilities, oppositional defiant and conduct disorders and mood and anxiety disorders is common in children and adults with this disorder and are associated with adversive academic and vocational outcomes and tremendous stress to families. Medication with dopaminergic and noradrenergic activity seems to reduce ADHD symptoms by blocking dopamine and norepinephrine reuptake. The aim of this review is to provide clinicians with a brief synopsis of the current under-standing about the etiology of ADHD, co-morbidity and associated problems, develop-mental course and intervention options. Parents understanding about the current data increases their consent to intervention, and the adherence to psychosocial and pharma-cological treatment.

Key words: Attention deficit - hyperactivity disorder, co-existing problems methyl-phenidate, atomoxetine, children.

45

, , , 115 27, . e-mail: aggskard@uoa.gr

CorrespodenceAggeliki Skardoutsou2nd Department of Pediatrics, University of Athens, P& A Kyriakou Childrens Hospital, Goudi, 115 27, Athens, Greecee-mail: aggskard@uoa.gr

- () 21 . 20 , . 21 . .

H 8-12% , , . (1). () . Diagnostic and Statistical Manual of the American Psychiatric Association (4th edition;DSM-IV) , , ( 1). . (2). (Hyperkinetic Disorder - HKD) (10 ) - International Classification of Diseases (10th edition; ICN -10) (3). DSM-IV (HKD) DSM-IV (4). D .

46

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47

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. (11). - (-) (12). . . , . , (12). .

48

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) H . 25% 50% (21). . . 4 7 (DRD4-7) in vitro

49

()

(22). 5 (DRD5) ( (DRD5 148bp ) (23) (DAT-10 3 ) (24). 1 (DRD1), 5- (5-HT (1B), ( Taq 1) (SNAP-25) (22). , . (16). (25).

) , , , , , , , (26,27,28). , , . (29). 70 , , , . (30). . ( DAT-10 ( ) (7). , , . . (, , ) . . . (22).

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50

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(2%) (1%) (14%). , , (1-31).

, , 40% , (32). , , , , . 3-5% , , , (33). .

(35). . (34). . (34, 36).

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51

.

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52

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, (42). . , , , 75 % (42,43,44). 2-3 (42-43) (48). , . 30 3-4 2-3 (42,43,44). 1.5 . , . 2.5 mg . . . , . 22% 78% 12 (43). 18mg 5 mg o 3 . H 54 mg 72 mg . . , , , ( ), () .

53

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- (Ritalin)

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18

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54

-

. . 2-3 , . . . 6-12 (49-50). (50). , , , , . . . . . Tourette. , , . . , . . (44). . . ( ) (4-48-51-53). . (4-47-48-51-53). - , (4). . . , (51-52). , , , , -, (42).

55

. , . . . . . . .

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57

31. Biederman J, Newcorn J, Spritch S. Commorbidity of attention deficit hyperactivity disorder with conduct, depressive anxiety and other disorders. Am J Psychiatry 1999;148 :564-577.

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58

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49. elsey DK, Summer CR, Casat CD et al. Once daily atomoxetine treatment for children with attention deficit hyperactivity disorder, including an assessment of evening and morning behavior; a double blind, placebo-controlled trial. Pediatrics 2004;114:(1)1-8.

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59

60

Abstract

X ,

Panagiota TriantafyllouCharikleia Chatzisevastou1st Department of Pediatrics, Aristotle University of Thes-saloniki, Hippokratio Hospital, Thessaloniki

REVIEW ARTICLES

1

, X

, 1. (genome-wide asso-ciation studies) . . HLA , -HLA . -. , 1.

: 1, ,

Genetics in Diabetes Mellitus type 1

Panagiota Triantafyllou, Charikleia Chatzisevastou

During the last years there has been dramatic progress in understanding the genetics, the autoimmune mechanisms and natural history of diabetes mellitus type 1. Genome-wide association studies have shown that there are at least four major and few minor genetic loci associated with the risk of diabetes type 1. Genes within HLA region seems to play the most important role, whereas, genes outside the HLA region may also con-tribute to the risk but their role is much less important. The majority of these loci appear to affect the immune system and the activation of T-cells, in particular. Elucidating the actual way that the products of these loci function could contribute in the understanding of how they affect the risk of diabetes type 1. Furthermore, these findings may improve our ability to predict and prevent diabetes type 1 through clinical applications.

Key-words: diabetes mellitus type 1, autoantibodies, genetic analysis

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

61

. 16, .. 53351, : 2310440100e-mail: ptriantafyllou@yahoo.com

CorrespodencePanagiota Triantafyllou16 Ethn. Antistaseos str, GR 53351, Thessaloniki, GreeceTel: +302310440100e-mail: ptriantafyllou@yahoo.com

1

1

, 1, - (3). 1, -1.

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62

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-1(%)

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63

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HLA 6 6p21.3 -1(3,10,13,21-24,27). HLA (Human Leukocyte Antigens) . HLA ( , )(27). -1 DR DQ(16,23-27). LA (): DR4-DQ8 DR3-DQ2, 90% -1(16,25-27). DR15-DQ6 1% -1 20% -1(16,25,30-32). DR-DQ -1. . , , -1 (22-23). CD8+ - (16,10,13,22,26). HLA-DR HLA-DQ -1 (33-37). , DR3 / DQ2 -. HLA-DR4 DQ8 . HLA . . - OD -1.

64

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, HLA .

-1 (INS) 11p15.5(16,23,38). DNA (DNA sequencing) (upstream) (VNTR: variable number of tandem repeat). INS VNTR (39). 3 (39). -1 (28-44 ), (138-159 ) (40). , (16). - . INS VNTR, , -1. INS VNTR . ( -), , -1 (10,16,26,32,41-42).

To -1 - (10,13,15,16,21,23-24,26). PTPN22, o 1p13 , Lyp. Lyp - -. Bottini . (43) 1858C/T -1, (44-48). 30,6% -1 21,3% . -1, . , , (49). , PTPN22 . -1 1858C/T - (10).

65

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(linkage studies) -1, NOD CTLA4 (cytotoxic T-lymphocyte-associated antigen 4) 2q33 -1(50). CTLA4 -, -. CTLA4 - -1(10,16,21,23-24,26).

HLA-DR HLA-DQ, , (7-9,15-16,21,51-58). (DR3-DQ2 DR4-DQ8) 1 20 -1 15 (59). / -1 55% (9,15-16,61). 2,3% . DAISY(51), -1 Denver 50% 5 . HLA , HLA. . , ( HLA) (3,23-24). , . , DAISY(51) . , 40% , 1 30 . . , -1, . -1. -. screening test .

66

1

HLA -1. -HLA . -. , -1.

1. Baker PR 2nd, Steck AK. The past, present, and future of genetic associations in type 1 diabetes. Curr Diab Rep 2011; 11(5):445-53.

2. Steck AK, Rewers MJ. Genetics of type 1 diabetes. Clin Chem 2011; 57(2):176-85.

3. Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. The New England jour-nal of medicine 2009; 360: 1646-1654.

4. Eisenbarth GS, Jeffrey J. The natural history of type 1A diabetes. Arquivos brasileiros de endocrinologia e metabologia 2008; 52: 146-155.

5. Nagamine K, Peterson P, Scott HS et al. Positional cloning of the APECED gene. Nature genetics 1997; 17: 393-398.

6. Bennett CL, Ochs HD. IPEX is a unique X-linked syndrome characterized by immune dysfunction, polyendocrinopathy, enteropathy, and a variety of autoimmune phenom-ena. Current opinion in pediatrics 2001; 13: 533-538.

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2: -1(24).

PGM1

PTPN22 1

RGS1

IL10

, IL18RAP

Intergenic

IFIH1

CTLA4

HLA

BACH2

C6orf173

SKAP2

COBL

GLIS3

IL2RA

PRKCQ

/ (Mb) (SNP)

1

1

1

1

2

2

2

2

4

6

6

6

7

7

9

10

10

63.9

114.2

190.8

205

12.6

24.5

162.9

204.4

25.7

32.7

91

126.7

26.9

51

4.3

6.1

6.4

rs2269241

rs2476601

rs2816316

rs3024505

rs1534422

rs2165738

rs3747517

rs231727

rs10517086

rs9272346

rs11755527

rs9388489

rs7804356

rs4948088

rs7020673

rs12251307

rs947474

70

1

/ (Mb) (SNP)

RNLS

INS

CD69

12q13

SH2B3

ZFP36L1

CTSH

CLEC16A

ORF; PRM3; TNP2

UMOD

IL27

CTRB2

DNAH2

GSDMB, ORMDL3

SMARCE1

PTPN2

PRKD2

SIRPG

Ubash3a

LOC729980

C1QTNF6

GAB3

EFR3B

AFF3

SLC11A1

10

11

12

12

12

14

14

15

16

16

16

16

16

17

17

17

18

19

20

21

22

22

X

2

2

2

90

2.1

9.8

54.8

111

68.3

97.6

77

11.1

11.3

20.3

28.4

73.8

7.6

35.3

36

12.8

51.9

1.6

42.7

28.9

35.9

153.6

25.3

100.2

2219.3

rs10509540

rs689

rs4763879

rs2292239; rs1701704

rs17696736

rs1465788

rs4900384

rs3825932

rs12708716

rs416603

rs12444268

rs4788084

rs7202877

rs16956936

rs2290400

rs7221109

rs2542151

rs425105

rs2281808

rs876498

rs5753037

rs229541

rs2664170

rs478222

rs9653442

rs3731865

71

/ (Mb) (SNP)

CCR5

IL2

CAPSL

LOC729653

HLA

AGER

TNFAIP3

TAGAP

6q27

IKZF1

CUX2

LMO7

DLK1

RASGRP1

CCR7

Trp53

FHOD3

CD226 18

PRKD2

FUT2

3

4

5

6

6

6

6

6

6

7

12

13

14

15

17

17

18

18

19

19

3 46.3

123.3

35.9

29.5

31.3

32.1

138

159.4

170.4

50.5

111.4

76

100.4

36.7

38.8

7.6

34.2

67.5

47.2

49.2

rs11711054

rs2069763

rs6897932

rs1592410

rs3094663

rs9469089

rs10499194

rs1738074

rs924043

rs10272724

rs1265564

rs539514

rs941576

rs17574546

rs7221109

n/a

rs2644261

rs763361

rs425105

rs601338

72

1

1: -1(4).

2: -1(53)

-

;

C-

C-

1973/4

1983/4

1988

1994

1998

2003

2004/5

2007/8

HLA

INS

HLA

CTLA-4

PTPN22

HLA

7

73

74

. 1, . 1, . 1, . 1, . 1, . 1, . 1, . 2, . 3, . -1, . 1

: (). () . : 48 (33 , 68,75%) 3,88 ( 0,37-13,97). (9 3 ).: (, , , HDL-- ) . , () ( ) HDL- ( 6 ), .: , , , - , , . , .

: , , .

Dysmetabolic syndrome manifestation is not related with therapy stages in acute lymphoblastic leukemia of childhood

E. Koultouki1, G. Trimis1, G. Lambrou1, M. Tsotra1, N. Tourkantoni1, K. Karamo-legou1, M. Adamaki1, J. Papassotiriou2, G. Chrousos3, F. Tzortzatou-Stathopou-lou1, M. Moschovi1

Background: Survivors of childhood cancer have an increased probability to present dys-metabolic syndrome (DS). Purpose of this study was to investigate the presence of DS in patients who undergo treatment for acute lymphoblastic leukemia (ALL) of childhood.

ORIGINAL ARTICLES

. 1

. 1

. 1

. 1

. 1

. 1

. 1

. -1

. 1

-, ,

. 2

,

. 3

, , ,

Abstract

75

& , 115 27, .. 2107467604, 6947193193Fax: 2107759167e-mail: lorikoultouki@hotmail.comCorrespondence E. Koultouki MD PhDThivon & Livadias, 115 27, AthensTel. 2107467604, 6947193193Fax: 2107759167e-mail: lorikoultouki@hotmail.com

E. Koultouki1

G. Trimis1

G. Lambrou1

M. Tsotra1

N. Tourkantoni1

K. Karamolegou1

M. Adamaki1

F. Tzortzatou-Stathopoulou1

M. Moschovi1

Haematology-Oncology Unit, 1st Department of Pediatrics, University of Athens, Aghia Sophia Childrens Hospital

J. Papassotiriou2

Department of Biochemistry, Aghia Sophia Childrens Hospital

G. Chrousos3

Endocrinology, Metabolism and Diabetes Units, First Department of Pediatrics, University of Athens, Aghia Sophia Childrens Hospital

Patients and Methods: The study included 48 patients with ALL (33 males, 68.7%) with a median age of 3.88 years (range 0.37-13.97). Measurements were done at diagnosis and in time intervals up to the end of therapy (9 measurements in 3 years).Results: During chemotherapy, no DS criteria (obesity, hypertriglyceridemia, hyperinsu-linemia, reduced HDL-cholesterol and hypertension) were detected in any patient. Values of these parameters were not correlated with treatment stages; however there was an increasing trend of body mass index (BMI) during therapy (till the end of follow-up) and a temporal increase of triglycerides together with a temporal decrease of HDL-cholesterol after the first cycle of therapy (up to 6 months), without overcoming the statistical sig-nificance.Conclusions: Young survivors of childhood ALL are at risk for obesity, insulin resistance, dyslipidemia, hypertension and, finally, full DS installation, several years after the comple-tion of therapy, without being evident during therapy, up to its completion (3 years). DS development soon after the end of chemotherapy and trends of increase or decrease of these markers during therapy indicate the need of individual approach and treatment of children with ALL, in order to prevent DS development.

Key words: children, leukemia treatment, dysmetabolic syndrome.

, , (1-3). , . , (GH), , , , , (4-6). 9.6 . , . , 45 . (7-10). , 6 (11). . , . , , -. . ,

=

=

=

=

=

76

-

3 (2006-2009), 62 - . , 6 , , 5 . , 48 (33 , 68,7%). 3,88 ( 0.37-13.97) 4,97 . : ( 0, CI 95%, 00.13), ~28 (CI 95%, 281.79), ~60 (CI 95%, 603.94), ~6 (180 , CI 95%, 1806.77), ~1 (365 , CI 95%, 3656.45), 1,5 (547 , CI 95%, 54710.52), ~2 (730 , CI 95%, 73034.95), 2,5 (912 , CI 95%, 91272) ~3 (1095 , CI 95%, 1095107.6). HOPDA (Haematology/Oncology Paediatric Department of Athens University) (HOPDA97) (2,12). ( 1). 28 . , , . . , , , . .

, , () . . 10-14 , . -700 C . 0,5 0,5 . . (kg/m2) () , (13). >97 , >75

77

Lipid Research Clinics Programme. , (15,16). . , C- (CRP) A (SAA), latex BN ProSpec (Dade Behring, Liederbach, ). (T4 TSH) Bayer ACS180 (Bayer Corporation, Tarry-town, NY, USA). IGF-1 chemi-luminescences (Nichols Institute Diagnostics, CA, USA). HbA1c HPLC (HA8121 HPLC system, Arkray Inc, Kyoto, Japan). (homeostasis model assessment, HOMA), ( x ) 22.5, U/ml mmol/L (17).

, . . , (National Choles-terol Education Programs Adult Treatment ) , (18). , . HOMA , (17). 1.

1: * .

HDL-C

>97

>95

95 (>18.7 U/ml 5-25 )

>95 ,

* : HDL-C: HDL-: , :

78

( ) ( ). Fisher (Fishers exact test) . t-test . O Pearson, Kendalls Tau Pearson. Cox . p

79

2. - (BMI) (A), (B), (C), HDL LDL (D) LDH ALP (E). LDH , .

(. -). . , , ( 1). . . ( 2) . ( 2). ~28 , ( 256.36, CI 95% 72.52, 78.51, CI 95% 78.51), . . ( 2C), , . HDL LDL ( 2D). LDH ( 2E). , . , . LDH . LDH ALP ( 2E).

80

Females

15

1

4

5

2

2

1

Total

48

3

13

13

9

2

7

% (overall)

31.25%

2.08%

8.33%

10.42%

4.17%

4.17%

2.08%

Median

3.88

0.72

2.45

3.83

5.78

7.63

12.82

%(within Group)

31.25%

33.33%

30.77%

38.46%

22.22%

100.00%

14.29%

StDev

3.42

0.20

0.39

0.46

0.56

0.28

1.74

Median

3.83

0.72

2.52

3.83

5.96

7.63

10.14

CI 95%

0.97

0.23

0.21

0.25

0.37

0.39

1.29

StDev

2.48

0.00

0.29

0.60

0.71

0.28

0.00

CI 95%

1.25

0.28

0.52

0.98

0.39

TABLE 2

2: . . .

Age at Diagnosis

Totals

Age

81

Total

48

3

13

13

9

2

average

4.97

0.64

2.45

3.69

5.87

7.63

StDev

3.42

0.20

0.39

0.46

0.56

0.28

CI 95%

0.97

0.23

0.21

0.25

0.37

0.39

Females

15

1

4

5

2

2

% (overall)

31.25%

2.08%

8.33%

10.42%

4.17%

4.17%

%(within Group)

31.25%

33.33%

30.77%

38.46%

22.22%

100.00%

Median

4.46

0.72

2.50

3.77

5.96

7.63

StDev

2.48

0.00

0.29

0.60

0.71

0.28

CI 95%

1.25

0.28

0.52

0.98

0.39

Age at Diagnosis

Totals

Age

82

, , . ( 3A), , . , ( 3B-3D). . SGOT GT

3. /.

3. /.

, SGPT . . LDH ( 3E). , ( 3F, 3G).

83

- . IGF1 . , , Pearson. , . , IGF1 ALP . GT . GT, LDH . , , , IGF1 ( 5). IGF1 GT, , . LDH. ( 5B). , .

4. (A), (B, C) LDH (D).

5. , IGF1 GT, , , LDL.

. , . . . , ( 4). ~28 , ( 4B, 4C). 3 5 . LDH 1-3 9 ( 4D). , , , .

84

6. (A). (B) LDL (C) ALP (D) .

. , . . 6 , ( 6), ( 6B) HDL LDL ( 6C) ALP LDH ( 6D). (R2=0.7), HDL (R2=0.81) ALP (R2=0.901). , , . .

() . , , HDL-,