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¢ÈÌËÓÈ·›· ¤Î‰ÔÛË Ù˘ EÏÏËÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ EÙ·ÈÚ›·˜ ¶Úfi‰ÚÔ˜ ∞. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜ ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘ ∫. ™ÙÂÊ·Ó›‰Ë˜ M¤ÏË ™. ∞Ó‰ÚÔÓ›ÎÔ˘ ª. ∞ÓıÚ·ÎfiÔ˘ÏÔ˜ ¶. ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘ °. µ·ÚÏ¿Ì˘ ∂. °·Ï·Ó¿Î˘ §. £ˆÌ·˝‰Ô˘ ª. ∫·Ó¿ÚÈÔ˘ A. K·ÙÙ¿Ì˘ ™. K›ÙÛÈÔ˘-∆˙¤ÏË ∞. ¶··‰ÔÔ‡ÏÔ˘ µ. ¶··Â˘·ÁÁ¤ÏÔ˘ ∞. ™È·ÌÔÔ‡ÏÔ˘-ª·˘Ú›‰Ô˘ ∞. ™˘Ú›ÁÔ˘-¶··‚·ÛÈÏ›Ԣ ∂. ÷ÚÌ·Ó‰¿ÚË ÀÔ‚ÔÏ‹ ∂ÚÁ·ÛÈÒÓ e-mail: hps@ath.forthnet.gr √‰ËÁ›Â˜ ÚÔ˜ ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜: http://www.e-child.gr/Instructions_ to_Authors_GR.pdf
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¶ÂÚȯfiÌÂÓ· ∞¡∞™∫O¶∏™∂π™ 1 ÃÔÚ‹ÁËÛË ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Û ·È‰È¿ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘: ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ∫. ∫·Ú·‚·Ó¿ÎË-∫·Ú·Ó¿ÛÈÔ˘ 10 £Âڷ›· Ì ·˘ÍËÙÈ΋ ÔÚÌfiÓË ÛÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi E. ∫Ô‡ÛÙ·, Ã. ÷Ù˙Ë·ı·Ó·Û›Ô˘†, A. ¶··ı·Ó·Û›Ô˘ 16 ¡ÂÔÁÓÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi ‚-·ÈÌÔÏ˘ÙÈÎfi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ µ Ã. ∆۷ηϛ‰Ë˜, ∞. ∆Ú·ÁÈ·ÓÓ›‰Ë˜, ¡. ¡ÈÎÔÏ·˝‰Ë˜ 23 ¶ÔÏ˘Û·Î¯·ÚȉÈο ·ÓÙÈÁfiÓ· – Û˘˙¢Á̤ӷ ÂÌ‚fiÏÈ·: ·ÓÔÛȷ΋ ÌÓ‹ÌË Î·È ·Ó·ÌÓËÛÙÈΤ˜ ‰fiÛÂȘ π.£. ∫·‚·ÏÈÒÙ˘
ºÈÏÔÏÔÁÈ΋ EÈ̤ÏÂÈ· ∂È̤ÏÂÈ· ÂÏÏËÓÈÎÒÓ ÎÂÈÌ¤ÓˆÓ ∫. ¶··¯Ú‹ÛÙÔ˘ EÈ̤ÏÂÈ· ·ÁÁÏÈÎÒÓ ÎÂÈÌ¤ÓˆÓ ™. ¡¿ÎÔ˘ EΉfiÙ˘ K. °ÚÈ‚¤·˜ ™˘ÓÙÔÓÈÛÙ‹˜ ∂ΉfiÛˆ˜ Communications In Practice A.E. ¶ÈÂÚ›·˜ 1∞ 144 51 MÂÙ·ÌfiÚʈÛË TËÏ.: 210 87 78 884 Fax: 210 87 78 822 I‰ÈÔÎÙ‹Ù˘ EÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ EÙ·ÈÚ›·© Mȯ·Ï·ÎÔÔ‡ÏÔ˘ 92 Aı‹Ó· 115 28 TËÏ.: 210 7771 140 210 7771 663 Fax: 210 7758 354 e-mail: hps@ath.forthnet.gr EÙ‹ÛÈ· ™˘Ó‰ÚÔÌ‹: 40 € EȉÈ΢fiÌÂÓÔÈ, ºÔÈÙËÙ¤˜: 20 € ∫ˆ‰ÈÎfi˜ ¢È‡ı˘ÓÛ˘ ∂ÔÙ›·˜ ªª∂: 3889
ISSN 0377-2551
∂ƒ∂À¡∏∆π∫∂™ ∂ƒ°∞™π∂™ 29 ÃÔÚ‹ÁËÛË ‰‡Ô ·ÓÙÈ-TNF Û΢·ÛÌ¿ÙˆÓ (etanercept Î·È adalimumab) Û ·È‰È¿ Ì Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·: 5 ¯ÚfiÓÈ· ÌÂÙ¿ ª. ∆Ú·¯·Ó¿, ¶. ¶Ú·ÙÛ›‰Ô˘-°Î¤ÚÙÛË, º. ∫·Ó·ÎÔ‡‰Ë-∆۷ηϛ‰Ô˘, ∫. ¢È¿Ê·, °. ¶·Ú‰·Ïfi˜, ª. ª·ÓÙÔ˘Ú¿ÎË 41 Obesity prevalence in children aged 8-13 years according to IOTF cutoffs, CDC growth charts and Z-BMI scores N. Mantzouranis, H. Douda, T. Pilianidis, S. Tokmakidis 46 ÃÚ‹ÛË Î·È Î·Ù¿¯ÚËÛË ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ Û ÊÔÈÙËÙ¤˜ ·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜ ™. ∞ÓÙˆÓÈ¿‰Ë˜, Ã. °È·‚Ú‹, ∂. ¶··Ì·Î·Ú›Ô˘, ∫. ™Ù·‡ÚÔ˘, ª. ∑¤Ú‚·, ∂. ¢ÈÔÓ˘ÛÔÔ‡ÏÔ˘, ∂. ª·ÎÚÔÁΛη, µ. ™·ÏˆÓ›‰Ë˜
∂¡¢π∞º∂ƒ√À™∂™ ¶∂ƒπ¶∆ø™∂π™ 51 梉ԸԷωÔÛÙÂÚÔÓÈÛÌfi˜ Ù‡Ô˘ 1 Û ‚Ú¤ÊÔ˜ Ã. ¢·ÛηÏÔÔ‡ÏÔ˘, £. ∆ÛÂÎÔ˘Ú¿, ∞. ∆ÛÈÏÈÌÈÁοÎË 55 π‰ÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË Û Ó·ÚÔ‡˜ ÂÊ‹‚Ô˘˜ Ì ·¯˘Û·ÚΛ· ∞. ºÈÏÈ›‰Ë, ™. ™ÙÂÊ·Ó¿ÎË, ª. ∞Ó·ÙÔÏȈٿÎË, °. µÏ·¯¿ÎË, Ã. º·ÓÔ˘ÚÈ¿Î˘, ∞. ∆ÛÈÏÈÌÈÁοÎË 60 ™˘ÁÁÂÓ‹˜ ¯˘ÏÔıÒڷη˜ Ì ˘Ô‰fiÚÈÔ Ô›‰ËÌ· ¿Óˆ ËÌ›ÛÂÔ˜ ÛÒÌ·ÙÔ˜ Û ÓÂÔÁÓfi Ì ۇӉÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ µ. ª·ÎÚ‹, ∞ÈÎ. ∫ˆÓÛÙ·ÓÙÈÓ›‰Ë, ª. ¶··‰ÔÔ‡ÏÔ˘, Ÿ. ¢Â‰Ô‡ÛË, ™. ∆¿ÓÙÚÔ˜, ∂. ∞Á·ËÙfi˜, ∞. °Ô‡Ó·Ú˘ ∫§π¡π∫√ ∫√Àπ∑ 66 ∂. ª·ÓÙ·‰¿Î˘, Õ. ∆Û·ÏΛ‰Ë˜, Õ. ƒ·Ì·Ù¿ÓË, ∂. ¶·Ú·Ûο΢, ∞. ÷Ù˙ËÌȯ·‹Ï ™À°Ãƒ√¡∞ £∂ª∞∆∞ µπ√™∆∞∆π™∆π∫∏™ 67 ¶ÚÔÔÙÈΤ˜ ÏËı˘ÛÌȷΤ˜ ÌÂϤÙ˜: Ë ÂÊ·ÚÌÔÁ‹ Ù˘ ÂȉËÌÈÔÏÔÁ›·˜ ÁÈ· ÙÔÓ Î·ıÔÚÈÛÌfi ÙˆÓ ·ÈÙÈÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ·È‰È·ÙÚÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ∂. ∫ÚÈÙÛ¤ÏË, ¢.∞. ∫·ÊÂÙ˙‹˜ ¡∂∞ ∞¶√ ∆√ ¢π∞¢π∫∆À√ 70 http://www.paidiatros.com ∞. ÷Ù˙Ë·Ó·Á‹˜
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Bimonthly Publication of the Greek Paediatric Society
Paediatriki
President A. Constantopoulos Editorial Board Editor-in-Chief C. Stefanidis Members S. Andronikou ª. ∞nthracopoulos P. Augoustides-Savvopoulou G. Varlamis ∂. Galanakis L. Thomaidou M. Kanariou A. Kattamis S. Kitsiou-Tzeli ∞. Papadopoulou V. Papaevagelou A. Siamopoulou-Mavridou A. Syrigou-Papavasiliou E. Charmandari
Volume 72 ñ Number 1 ñ January-February 2009
Contents REVIEW ARTICLES 1 rhGH treatment of children with growth hormone deficiency: factors affecting final height K. Karavanaki-Karanassiou 10 Growth hormone treatment in Prader-Willi syndrome E. Kousta, C. Hadjiathanasiou†, A. Papathanasiou
e-mail: hps@ath.forthnet.gr
16 Newborn infections from group B Streptococcus C. Tsakalidis, A. Tragiannidis, N. Nikolaidis
Instructions to authors: http://www.e-child.gr/paediatriki/ iae.pdf
23 Polysaccharide antigens – conjugated vaccines: immune memory and anamnestic doses π.T. Kavaliotis
Manuscript submission
Manuscript Editing Greek Editing K. Papachristou English Editing S. Nakou Publisher K. Griveas Publishing Coordinator Communications In Practice S.A. 1∞ Pierias St. GR - 144 51, Metamorfossi Tel.: +30 210 87 78 884 Fax: +30 210 87 78 822 Owner Greek Paediatric Society© 92 Michalakopoulou St. GR - 115 28, Athens Tel.: +30 210 7771 140 +30 210 7771 663 Fax: +30 210 7758 354 e-mail: hps@ath.forthnet.gr Annual Subscription All foreign countries: US $ 50
ORIGINAL ARTICLES
CASE REPORTS 51 Type 1 pseudohypoaldosteronism in an infant C. Daskalopoulou, T. Tsekoura, A. Tsilimigaki 55 Idiopathic intracranial hypertension in young adolescents with obesity A. Filippidi, S. Stefanaki, M. Anatoliotaki, G. Vlachaki, C. Fanouriakis, A. Tsilimigaki 60 Congenital chylothorax and subcutaneous oedema in a neonate with superior vena cava syndrome V. Makri, A. Konstantinidi, M. Papadopoulou, O. Dedousi, S. Tantros, E. Agapitos, A. Gounaris CLINICAL QUIZ 66 E. Mantadakis, A. Tsalkidis, A. Ramatani, E. Paraskakis, A. Chatzimichael
29 Administration of two anti-TNF agents (etanercept and adalimumab) in children with juvenile idiopathic arthritis: a 5-year follow-up study M. Trachana, P. Pratsidou-Gertsi, F. Kanakoudi-Tsakalidou, C. Diafa, G. Pardalos, M. Bantouraki
CURRENT ISSUES OF BIOSTATISTICS
41 Obesity prevalence in children aged 8-13 years according to IOTF cutoffs, CDC growth charts and Z-BMI scores N. Mantzouranis, H. Douda, T. Pilianidis, S. Tokmakidis
NEWS FROM THE INTERNET
46 Use and abuse of substances by young adult students of the health professions S. Mantoudis, L. Thomaidis
67 Prospective cohort studies: the application of epidemiology in order to identify the potential determinants of paediatric diseases E. Critselis, D.A. Kafetzis
70 http://www.paidiatros.com A. Hadjipanayis
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ÃÔÚ‹ÁËÛË ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Û ·È‰È¿ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘: ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ∫. ∫·Ú·‚·Ó¿ÎË-∫·Ú·Ó¿ÛÈÔ˘ ¶ÂÚ›ÏË„Ë: H ·ÚÔ‡Û· ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·ÛÎfiËÛË ·Ó·Ê¤ÚÂÙ·È ÛÙËÓ ·ÈÙÈÔÏÔÁ›· Ù˘ ·Ó¿ÚÎÂÈ·˜ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GH) ÛÙ· ·È‰È¿, ÛÙËÓ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· Ì ·ÓıÚÒÈÓË ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ·˘ÍËÙÈ΋ ÔÚÌfiÓË (rhGH), ηıÒ˜ Î·È ÛÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· (∆∞). √ ÂÙ‹ÛÈÔ˜ Ú˘ıÌfi˜ ·‡ÍËÛ˘ (∂ƒ∞) ηٿ ÙÔÓ 1Ô ¯ÚfiÓÔ ·ÁˆÁ‹˜ ·ÚÔ˘ÛÈ¿˙ÂÈ ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ÙË ¯ÚÔÓÔÏÔÁÈ΋ Î·È ÔÛÙÈ΋ ËÏÈΛ· ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜. ∞fi ÙȘ ·Ú·Ì¤ÙÚÔ˘˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙÔ ∆∞, ÛËÌ·ÓÙÈÎfiÙÂÚ˜ Â›Ó·È ÙÔ ‡„Ô˜ Î·È Ë ËÏÈΛ· ¤Ó·Ú͢ ·ÁˆÁ‹˜, ÙÔ ‡„Ô˜ ¤Ó·Ú͢ Ù˘ ‹‚˘ Î·È ÙÔ ·Ó¿ÛÙËÌ· ÙˆÓ ÁÔÓ¤ˆÓ. ∆Ô Û˘ÓËı¤ÛÙÂÚÔ ·›ÙÈÔ ÌË ÈηÓÔÔÈËÙÈ΋˜ ·ÓÙ·fiÎÚÈÛ˘ ÛÙË ıÂڷ›· Ì rhGH Â›Ó·È Ë ÌË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÁˆÁ‹. ™˘ÌÂÚ·ÛÌ·ÙÈο, Â›Ó·È ‰˘Ó·Ùfi Ó· ÂÈÙ¢¯ı› Ê˘ÛÈÔÏÔÁÈÎfi ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· Û ·È‰È¿ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GHD) Ì ÙË ¯ÔÚ‹ÁËÛË Û˘Ì‚·ÙÈÎÒÓ ‰fiÛÂˆÓ rhGH, Ì ÙËÓ ÂÓˆÚ›˜ ¤Ó·ÚÍË Ù˘ ·ÁˆÁ‹˜, ÙË ÛÙÂÓ‹ ·Ú·ÎÔÏÔ‡ıËÛË, ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ Î·ıËÌÂÚÈÓ‹ ¯ÔÚ‹ÁËÛË, ηıÒ˜ Î·È Ì ›Ù¢ÍË ÈηÓÔÔÈËÙÈÎÔ‡ ‡„Ô˘˜ ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ÂÊ˂›·˜.
B’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ «¶. & ∞. ∫˘ÚÈ·ÎÔ‡», ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ∫˘Úȷ΋ ∫·Ú·‚·Ó¿ÎË∫·Ú·Ó¿ÛÈÔ˘ kkarav@yahoo.gr B’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ «¶. & ∞. ∫˘ÚÈ·ÎÔ‡» °Ô˘‰‹ 11527, ∞ı‹Ó·
§¤ÍÂȘ ÎÏÂȉȿ: ∞Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ıÂڷ›· Ì ·ÓıÚÒÈÓË ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ·˘ÍËÙÈ΋ ÔÚÌfiÓË, Ú˘ıÌfi˜ ·‡ÍËÛ˘, ÙÂÏÈÎfi ·Ó¿ÛÙËÌ·.
rhGH treatment of children with growth hormone deficiency: factors affecting final height K. Karavanaki-Karanassiou Abstract: This is a review of the aetiology of growth hormone deficiency (GHD) in childhood, its response to treatment with recombinant human growth hormone (rhGH), and the factors that affect the final height (FH). ∆he growth velocity (GV) during the first year of treatment with rhGH is negatively correlated with chronological and bone age at treatment initiation. Among the factors affecting FH the most important are the genetically determined height potential of the patient, early age at diagnosis, height at initiation of treatment, correction of height deficit prior to the onset of puberty, daily administration of rhGH treatment, higher doses of rhGH and longer duration of treatment. Lack of compliance with the treatment is the most common cause of inadequate response to rhGH therapy in children with GHD. In conclusion, normal FH in children with GHD can be achieved with conventional doses of rhGH when treatment is initiated early, compliance is assured by close follow-up and a satisfactory height is attained prior to the onset of puberty.
2nd Department of Paediatrics, University of Athens, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece Correspondence: Kyriaki KaravanakiKaranassiou kkarav@yahoo.gr 2nd Department of Paediatrics, University of Athens, “P. & A. Kyriakou” Children’s Hospital Goudi 11527, Athens, Greece
Key words: Growth hormone deficiency, human recombinant growth hormone therapy, growth velocity, final height.
AÈÙÈÔÏÔÁ›·-‰È¿ÁÓˆÛË ·Ó¿ÚÎÂÈ·˜ GH ∏ ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (growth hormone deficiency, GHD), ÂÊfiÛÔÓ ‰ÂÓ ‰È·ÁÓˆÛı› Î·È ‰ÂÓ ·ÓÙÈÌÂÙˆÈÛı› Ì ıÂڷ›· ˘ÔηٿÛÙ·Û˘ Ì ·ÓıÚÒÈÓË ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ·˘ÍËÙÈ΋ ÔÚÌfiÓË (recombinant human growth hormone, rhGH), Ô‰ËÁ› Û ÛËÌ·ÓÙÈο ¯·ÌËÏfi ·Ó¿ÛÙËÌ·. ∏ ·Ó¿ÚÎÂÈ· GH ‰È·ÎÚ›ÓÂÙ·È Û ȉÈÔ·ı‹ Î·È ÔÚÁ·ÓÈ΋ (1). I‰ÈÔ·ı‹˜ ·Ó¿ÚÎÂÈ· GH (idiopathic growth hormone deficiency, IGHD) ‰È·ÁÈÁÓÒÛÎÂÙ·È fiÙ·Ó Î·Ù¿ ÙÔÓ ¤ÏÂÁ¯Ô ‰ÂÓ ‰È·ÈÛÙÒÓÔÓÙ·È ·Ó·ÙÔÌÈΤ˜ ‹ ÁÂÓÂÙÈΤ˜
·ÓˆÌ·Ï›Â˜, Û ·ÓÙȉȷÛÙÔÏ‹ Ì ÙËÓ ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (organic growth hormone deficiency, OGHD), ηٿ ÙËÓ ÔÔ›· ‰È·ÈÛÙÒÓÔÓÙ·È ÔÈΛϷ ·›ÙÈ· (¶›Ó·Î·˜ 1). ™Â ·È‰È¿ Ì IGHD ÌÔÚ› Ó· ·ÔÎ·Ï˘ÊıÔ‡Ó ÚÔ‚Ï‹Ì·Ù· ηٿ ÙÔÓ ÙÔÎÂÙfi (ÂÚÈÁÂÓÓËÙÈ΋ ·ÛÊ˘Í›·, Èۯȷ΋ ÚÔ‚ÔÏ‹), ηıÒ˜ ›Û˘ Î·È Î·Ù¿ ÙËÓ ÂÁ΢ÌÔÛ‡ÓË (·ÂÈÏÔ‡ÌÂÓË Î‡ËÛË, ·ÈÌÔÚÚ·Á›Â˜, ۷ί·Ú҉˘ ‰È·‚‹Ù˘ ·ËÛ˘, Ïԛ̈ÍË) (2,3). ∂Âȉ‹ Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ Ù˘ ˘Ôı·Ï·ÌÔ-˘ÔÊ˘Ûȷ΋˜ ÂÚÈÔ¯‹˜ ‰È·ÈÛÙÒÓÔÓÙ·È Î·È ¯ˆÚ›˜ ÂÚÈÁÂÓÓËÙÈ΋ ¶·È‰È·ÙÚÈ΋ 2009;72:1-9
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∫˘Úȷ΋ ∫·Ú·‚·Ó¿ÎË-∫·Ú·Ó¿ÛÈÔ˘
¶›Ó·Î·˜ 1. ∞›ÙÈ· ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ 1. π‰ÈÔ·ı‹˜ ·Ó¿ÚÎÂÈ· GH ·. ªÂ ‹ ¯ˆÚ›˜ ÈÛÙÔÚÈÎfi ÂÚÈÁÂÓÓËÙÈ΋˜ ˘ÔÍ›·˜ ‚. ÕÁÓˆÛÙÔ ÂÚÈÁÂÓÓËÙÈÎfi ÈÛÙÔÚÈÎfi Á. ¡Â˘ÚÔÂÎÎÚÈÙÈ΋ ‰È·Ù·Ú·¯‹ GH 2. OÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· GH ·. ™˘ÁÁÂÓ‹˜ ñ °ÔÓȉȷ΋ ‚Ï¿‚Ë (GH1, GHRHR, POU1F1, PROP1, LHX4, SOX3) ñ ™‡Ó‰ÚÔÌ· (Fanconi, ÂÎÙÔ‰ÂÚÌÈ΋ ‰˘ÛÏ·Û›·) ñ ™˘ÁÁÂÓ›˜ ÏÔÈÌÒÍÂȘ (Û˘ÁÁÂÓ‹˜ ÂÚ˘ıÚ¿ Î.¿.) ñ ∞ӈ̷ϛ˜ Ù˘ ̤Û˘ ÁÚ·ÌÌ‹˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ - ™‡Ó‰ÚÔÌÔ ÎÂÓÔ‡ ÙÔ˘ÚÎÈÎÔ‡ ÂÊÈ›Ԣ - ∞ÁÂÓÂÛ›· ÌÂÛÔÏÔ‚›Ô˘ - ¢˘ÛÏ·Û›· ÙÔ˘ ‰È·Ê·ÓÔ‡˜ ‰È·ÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ ÌÂÛÔÏÔ‚›Ô˘ Î·È Ù˘ ÔÙÈ΋˜ Û˘Û΢‹˜ (Septooptic dysplasia) - OÏÔÚÔÛÂÁÎÂÊ·Ï›· - ¢È·ÙÔÌ‹ ÙÔ˘ Ì›Û¯Ô˘ Ù˘ ˘fiÊ˘Û˘ - ™‡Ó‰ÚÔÌÔ ÌÔÓ‹ÚÔ˘˜ ÙÔ̤· ¿Óˆ ÁÓ¿ıÔ˘ - ÀÂÚˆÈÔÛ¯ÈÛÙ›· - ™˘ÁÁÂÓ‹˜ ˘‰ÚÔΤʷÏÔ˜ - ∞Ú·¯ÓÔÂȉ›˜ ·ÛÙÂȘ ‚. ∂›ÎÙËÙË ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· GH ñ ŸÁÎÔÈ ˘Ôı·Ï·ÌÔ-˘ÔÊ˘Ûȷ΋˜ ÂÚÈÔ¯‹˜ (ÎÚ·ÓÈÔÊ·Ú˘ÁÁ›ˆÌ·, ‰˘ÛÁÂỨӈ̷, ·Ì¿Úو̷ Î.¿.) ñ ∂Ó‰ÔÎÚ¿ÓÈÔÈ fiÁÎÔÈ ÂÎÙfi˜ ÙÔ˘ÚÎÈÎÔ‡ ÂÊÈ›Ԣ (·ÛÙÚÔ·Ùو̷, ÂÂÓ‰‡ÌˆÌ·, ÁÏÔ›ˆÌ·, Ì˘ÂÏÔ‚Ï¿Ûو̷, fiÁÎÔÈ ÚÈÓÔÊ¿Ú˘ÁÁ· Î.¿.) ñ ∞ÎÙÈÓÔ‚ÔÏ›· Â͈ÎÚ·ÓÈ·ÎÒÓ Î·ÎÔËıÂÈÒÓ (Ï¢¯·ÈÌ›·, ϤÌʈ̷, Û˘Ì·Á›˜ fiÁÎÔÈ) ñ ÕÏÏ· ·›ÙÈ· (ÙÚ·‡Ì· ÎÚ·Ó›Ô˘, Ïԛ̈ÍË ∫¡™, ›ÎÙËÙÔ˜ ˘‰ÚÔΤʷÏÔ˜, ÈÛÙÈÔ·ÙÙˆÛË, ¯ÚfiÓÈ· ÎÔÎÎȈ̷Ù҉˘ ÓfiÛÔ˜, ·ÁÁÂȷΤ˜ ·ÓˆÌ·Ï›Â˜)
οΈÛË, Ù›ıÂÙ·È Ë ˘fiÓÔÈ· Ì‹ˆ˜ ÔÈ Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ Ù˘ ·Ó¿Ù˘Í˘ Ù˘ ˘Ôı·Ï·ÌÔ-˘ÔÊ˘Ûȷ΋˜ ÂÚÈÔ¯‹˜ ‰ÂÓ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ·ÏÏ¿ ·›ÙÈÔ Ù˘ ÂÚÈÁÂÓÓËÙÈ΋˜ οΈÛ˘ (4). ∆· ·È‰È¿ Ì ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· GH ‰È·ÎÚ›ÓÔÓÙ·È Û ÂΛӷ ÌÂ Û˘ÁÁÂÓ‹ ÔÚÁ·ÓÈ΋ ‚Ï¿‚Ë (ÁÔÓȉȷ΋ ‚Ï¿‚Ë, Û‡Ó‰ÚÔÌ·, ·ÓˆÌ·Ï›Â˜ Ù˘ ̤Û˘ ÁÚ·ÌÌ‹˜ Î.Ï.) (3) Î·È Û ›ÎÙËÙË ÔÚÁ·ÓÈ΋ ‚Ï¿‚Ë (fiÁÎÔÈ, ·ÎÙÈÓÔ‚ÔÏ›· Î.Ï.) (¶›Ó·Î·˜ 1). H ‰È¿ÁÓˆÛË Ù˘ ·Ó¿ÚÎÂÈ·˜ GH Ù›ıÂÙ·È fiÙ·Ó Û ‰‡Ô ‰È·‰Ô¯ÈΤ˜ ‰˘Ó·ÌÈΤ˜ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘ GH ÔÈ ÙÈ̤˜ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Â›Ó·È ¯·ÌËϤ˜. ∆Ô fiÚÈÔ ÙÔ˘ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ¤¯ÂÈ ÔÚÈÛı› Ì¿ÏÏÔÓ ·˘ı·›ÚÂÙ· ˆ˜ ̤ÁÈÛÙË ÙÈÌ‹ GH Ï¿ÛÌ·ÙÔ˜ >10 ng/ml ‹ >20 mU/L ηٿ ÙȘ ‰˘Ó·ÌÈΤ˜ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘ (5).
¶·Ú¿ÌÂÙÚÔÈ ÛˆÌ·ÙÈ΋˜ ·‡ÍËÛ˘ ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ rhGH √È ÌÂÙÚ‹ÛÂȘ ÙÔ˘ ‡„Ô˘˜ Î·È ÙÔ˘ ÂÙ‹ÛÈÔ˘ Ú˘ıÌÔ‡ ·‡ÍËÛ˘ (∂ƒ∞) ÙÔ˘ οı ·È‰ÈÔ‡ ÂÎÊÚ¿˙ÔÓÙ·È Û ‰Â›ÎÙ˜ ÛÙ·ıÂÚ‹˜ ·fiÎÏÈÛ˘ (Standard Deviation Score, SDS), Ì ‚¿ÛË ÙË ¯ÚÔÓÔÏÔÁÈ΋ ËÏÈΛ· Î·È ÙÔ Ê‡ÏÔ. √ ‰Â›ÎÙ˘ ·˘Ùfi˜ ‰Â›¯ÓÂÈ fiÛ˜ ÛÙ·ıÂÚ¤˜ ·ÔÎÏ›ÛÂȘ ·fi ÙÔÓ Ì¤ÛÔ fiÚÔ ‚Ú›ÛÎÂÙ·È ÙÔ ‡„Ô˜ ÙÔ˘ ·È‰ÈÔ‡ Î·È ˘ÔÏÔÁ›˙ÂÙ·È ·fi ÙÔÓ Ù‡Ô SDS = (̤ÛË ÙÈÌ‹ ‡„Ô˘˜-X)/SD [fiÔ˘ à = ‡„Ô˜, ̤ÛË ÙÈÌ‹ Paediatriki 2009;72:1-9
‡„Ô˘˜ = Ë Ì¤ÛË ÙÈÌ‹ ÙÔ˘ ‡„Ô˘˜ Ô˘ ·ÓÙÈÛÙÔȯ› ÛÙËÓ ËÏÈΛ· Î·È ÛÙÔ Ê‡ÏÔ ÙÔ˘ ·È‰ÈÔ‡ (·fi ›Ó·Î˜) Î·È SD = Ë ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË Ù˘ ›‰È·˜ ËÏÈΛ·˜]. ∏ ·Ó¿ÚÎÂÈ· Ù˘ GH (ȉÈÔ·ı‹˜ GHD) ÂΉËÏÒÓÂÙ·È Û˘Ó‹ıˆ˜ Ì ˘ÔÁÏ˘Î·ÈÌ›· ÛÙÔ˘˜ ÚÒÙÔ˘˜ Ì‹Ó˜ ˙ˆ‹˜ Î·È Ì ÂÏ¿ÙÙˆÛË ÙÔ˘ Ú˘ıÌÔ‡ ·Ó¿Ù˘Í˘ (Eƒ∞<3 SDS) ÌÂÙ¿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ. ∏ ¤ÏÏÂÈ„Ë GH ÛÙÔ˘˜ ÚÒÙÔ˘˜ Ì‹Ó˜ ˙ˆ‹˜ ‰ÂÓ ÂËÚ¿˙ÂÈ ÙÔ Ì‹ÎÔ˜/‡„Ô˜ ÙÔ˘ ·È‰ÈÔ‡, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÛÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ˙ˆ‹˜ Ë ·‡ÍËÛË Â›Ó·È ¿ÌÂÛ· ÂÍ·ÚÙË̤ÓË ·fi ÙË ‰È·ÙÚÔÊ‹. ∞ÓÙ›ıÂÙ·, ÛÙËÓ ÔÚÁ·ÓÈ΋ GHD, ÏfiÁˆ fiÁÎˆÓ ÂÁÎÂÊ¿ÏÔ˘ ‹ ·ÎÙÈÓÔ‚ÔÏ›·˜ ÎÚ·Ó›Ô˘ ˆ˜ › Ï¢¯·ÈÌ›·˜, fiÔ˘ ÚÔηÏÂ›Ù·È Â›ÎÙËÙË ‚Ï¿‚Ë ÛÙÔÓ ˘Ôı¿Ï·ÌÔ Î·È ÛÙËÓ ÚfiÛıÈ· ˘fiÊ˘ÛË, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·Ù·Ú·¯‹ ÛÙËÓ ¤ÎÎÚÈÛË GH, Ë ˘fiÓÔÈ· Ù›ıÂÙ·È ÏfiÁˆ Ì›ˆÛ˘ ÙÔ˘ ∂ƒ∞ Û ·È‰› Ì ÚÔËÁÔ‡ÌÂÓË Ê˘ÛÈÔÏÔÁÈ΋ ·‡ÍËÛË (6). ∏ ˘fiÓÔÈ· ·˘Ù‹ ÂÓÈÛ¯‡ÂÙ·È fiÙ·Ó ‰ÂÓ ˘¿Ú¯ÂÈ ıÂÙÈÎfi ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi (ÔÈ ÁÔÓ›˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜) Î·È ÔÈ ‰È·ÛÙ¿ÛÂȘ ÙˆÓ ·È‰ÈÒÓ Î·Ù¿ ÙË Á¤ÓÓËÛË Î·ıÒ˜ Î·È ÔÈ Û˘Óı‹Î˜ ÙÔ˘ ÙÔÎÂÙÔ‡ Â›Ó·È Ê˘ÛÈÔÏÔÁÈΤ˜ (7). ™ÙÔÓ ¶›Ó·Î· 2 ·Ó·Ê¤ÚÔÓÙ·È Â˘Ú‹Ì·Ù· ‰È·ÊfiÚˆÓ ÌÂÏÂÙÒÓ (8-12) Ô˘ ‰Â›¯ÓÔ˘Ó fiÙÈ Ë Ì¤ÛË ¯ÚÔÓÔÏÔÁÈ΋ ËÏÈΛ· ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜ Ì rhGH Û ·ÛıÂÓ›˜ Ì IGHD Î˘Ì·›ÓÂÙ·È ·fi 1,9 ¤ˆ˜ 10,1 ¤ÙË Î·È Ë Ì¤ÛË ÙÈÌ‹ Ù˘ SDS ÙÔ˘ ‡„Ô˘˜ ·fi -4,5 ¤ˆ˜ -2,5.
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·3
3
¶·È‰È¿ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘
¶›Ó·Î·˜ 2. ¢Â‰Ô̤ӷ ·ÛıÂÓÒÓ Ì ·Ó¿ÚÎÂÈ· GH ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜ Ì rhGH ªÂϤÙË Ranke (1991) De Muink (1992) Boersma (1995) Karavanaki Î·È Dacou (2001) Ranke (2001)
n 289 21 26 100 265
XH (¤ÙË) SDS ‡„Ô˘˜ (̤ÛË ÙÈÌ‹) (̤ÛË ÙÈÌ‹) 7,0 6,8 1,4 10,1 1,9 7,5
-2,8 -3,6 -4,1 -2,9 -3,1 -2,5
XH = ÃÚÔÓÔÏÔÁÈ΋ ËÏÈΛ· ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜ Ì rhGH SDS ‡„Ô˘˜ = ™Ù·ıÂÚ‹ ·fiÎÏÈÛË ‡„Ô˘˜ ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜
™Â ÛËÌ·ÓÙÈÎfi ·ÚÈıÌfi ·È‰ÈÒÓ, Ë IGHD ‰È·ÁÈÁÓÒÛÎÂÙ·È Û ËÏÈΛ· ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 6,8 ÂÙÒÓ, ÂÓÒ Û ÌÈÎÚfi ·ÚÈıÌfi ·È‰ÈÒÓ Ë ‰È¿ÁÓˆÛË Ù›ıÂÙ·È ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ·. ™Â ·È‰È¿ Ì ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· GH ÏfiÁˆ fiÁÎˆÓ ÂÁÎÂÊ¿ÏÔ˘ Î·È Ù˘ Û˘ÓÔ‰Ô‡ Ï‹„˘ ·ÎÙÈÓÔ‚ÔÏ›·˜, ·Ú·ÙËÚÂ›Ù·È ·Ú¯Èο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙÔ˘ ∂ƒ∞ Î·È ÚÔԉ¢ÙÈο, 2-3 ¯ÚfiÓÈ· ÌÂÙ¿ ÙË ıÂڷ›· ÙÔ˘ fiÁÎÔ˘, Ì›ˆÛË Ù˘ SDS ‡„Ô˘˜ (¤ˆ˜ -2,5 SDS). ∏ ‰È·›ÛÙˆÛË Ù˘ Ì›ˆÛ˘ ÙÔ˘ ∂ƒ∞ ÛÙ· ·È‰È¿ ·˘Ù¿ ·ÔÙÂÏ› ¤Ó‰ÂÈÍË ÁÈ· ÔÚÌÔÓÈ΋ ‰ÈÂÚ‡ÓËÛË Î·È ·ÓÙÈÌÂÙÒÈÛË (13).
¢ÔÛÔÏÔÁ›· rhGH ¶·Ï·ÈfiÙÂÚ· Ë GH ¯ÔÚËÁÔ‡ÓÙ·Ó 2-3 ÊÔÚ¤˜/ ‚‰ÔÌ¿‰· Î·È Û ÛÙ·ıÂÚ‹ ‰ÔÛÔÏÔÁ›· Û IU (12 IU/‚‰ÔÌ¿‰· Û 3 ‰fiÛÂȘ). ŒÙÛÈ, Ù· ·¯‡Û·Úη ·È‰È¿ ¤·ÈÚÓ·Ó ÌÈÎÚfiÙÂÚË ‰fiÛË Î·È Ù· ÏÂÙfiۈ̷ ÌÂÁ·Ï‡ÙÂÚË ‰fiÛË. ∫·Ù¿ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, Ë ‰fiÛË ˘ÔÏÔÁ›˙ÂÙ·È ·Ó¿ kg ‹ ·Ó¿ m2 ÂÈÊ·Ó›·˜ ÛÒÌ·ÙÔ˜ (14). M ÙËÓ ÂÈÛ·ÁˆÁ‹ Ù˘ ·ÓıÚÒÈÓ˘ ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (rhGH) (3IU/mg), Ë ‰ÔÛÔÏÔÁ›· ÙÚÔÔÔÈ‹ıËΠ۠IU/kg/‚‰ÔÌ¿‰· ‹ Û mg/kg/‚‰ÔÌ¿‰· Î·È ¯ÔÚËÁÂ›Ù·È Î·ıËÌÂÚÈÓ¿. ∏ Û˘ÓÈÛÙÒÌÂÓË ·Ú¯È΋ ‰ÔÛÔÏÔÁ›· Ù˘ rhGH ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ì IGHD Â›Ó·È 0,18-0,30 mg/kg/‚‰ÔÌ¿‰· (ÌÂ Û˘ÓËı¤ÛÙÂÚË ÙË ‰ÔÛÔÏÔÁ›· 0,25 mg/kg/‚‰ÔÌ¿‰·) ¯ÔÚËÁÔ‡ÌÂÓË Û 7 ËÌÂÚ‹ÛȘ ‰fiÛÂȘ. Œ¯ÂÈ ·Ô‰Âȯı› fiÙÈ Ë ·‡ÍËÛË Â›Ó·È ·Ó¿ÏÔÁË ÙÔ˘ ÏÔÁ·Ú›ıÌÔ˘ Ù˘ ‰fiÛ˘, ·ÏÏ¿ Ë Î·ıËÌÂÚÈÓ‹ ¯ÔÚ‹ÁËÛË Â›Ó·È ÈÔ ÛËÌ·ÓÙÈ΋ Û˘ÁÎÚÈÙÈο Ì ÙÔ ·Ï·ÈfiÙÂÚÔ ıÂڷ¢ÙÈÎfi Û¯‹Ì· ¯ÔÚ‹ÁËÛ˘ Ù˘ rhGH 3 ÊÔÚ¤˜/‚‰ÔÌ¿‰·. ŒÙÛÈ, ÌÈ· ÌÂϤÙË (15) ·¤‰ÂÈÍ fiÙÈ ÔÌ¿‰· ·ÛıÂÓÒÓ ˘fi ·ÁˆÁ‹ Ì rhGH Û ‰fiÛË 0,30 mg/kg/‚‰ÔÌ¿‰· Î·È Î·ıËÌÂÚÈÓ‹ ¯ÔÚ‹ÁËÛË Î¤Ú‰ÈÛ 9,7 cm ÂÚÈÛÛfiÙÂÚÔ ‡„Ô˜ Û ‰È¿ÛÙËÌ· 4 ÂÙÒÓ, Û˘ÁÎÚÈÙÈο Ì ÂΛÓÔ˘˜ Ô˘ ÂÏ¿Ì‚·Ó·Ó ÙËÓ ·ÁˆÁ‹ 3 ÊÔÚ¤˜/‚‰ÔÌ¿‰· (38,4 ¤Ó·ÓÙÈ 28,7 cm, p<0,0002), Ì ·ÚfiÌÔÈ·
ÂͤÏÈÍË Ù˘ ÔÛÙÈ΋˜ ËÏÈΛ·˜ Î·È ¯ˆÚ›˜ ÂÈÙ¿¯˘ÓÛË Ù˘ ‹‚˘.
∞ÓÙ·fiÎÚÈÛË ÛÙËÓ ·ÁˆÁ‹ Ì rhGH ∞) ™ÙËÓ ÚÔÂÊË‚È΋ ÂÚ›Ô‰Ô ∏ Ù˘È΋ ·¿ÓÙËÛË ÛÙË ıÂڷ›· ·È‰ÈÔ‡ Ì IGHD ÛÙË Û˘ÓÈÛÙÒÌÂÓË ‰ÔÛÔÏÔÁ›· Î·È Û ηıËÌÂÚÈÓ‹ ¯ÔÚ‹ÁËÛË Â›Ó·È Ë ·‡ÍËÛË ÙÔ˘ ∂ƒ∞ ·fi 3-4 cm/¯ÚfiÓÔ Û 8,6-13,3 cm/¯ÚfiÓÔ ÙÔÓ 1Ô ¯ÚfiÓÔ ·ÁˆÁ‹˜ (‰ËÏ·‰‹ ÂÈÙ¿¯˘ÓÛË ÙÔ˘ Ú˘ıÌÔ‡ ·‡ÍËÛ˘ ‰ÈÏ¿ÛÈ· ˆ˜ ÙÂÙÚ·Ï¿ÛÈ· ÂΛӢ ÚÔ ·ÁˆÁ‹˜) (16) Î·È Û 7-9 cm/¯ÚfiÓÔ ·ÓÙ›ÛÙÔȯ· ÙÔÓ 2Ô Î·È 3Ô ¯ÚfiÓÔ ·ÁˆÁ‹˜ (17). ªÂ ÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ, ·Ú·ÙËÚÂ›Ù·È ÛÙ·‰È·Î‹ Ì›ˆÛË Ùo˘ ∂ƒ∞, Ô˘ ÂÍÈÛÒÓÂÙ·È Ì ÙÔÓ Ê˘ÛÈÔÏÔÁÈÎfi ∂ƒ∞ ÁÈ· ÙËÓ ËÏÈΛ· Î·È ÙÔ Ê‡ÏÔ (17). ¶·ÚfiÌÔÈ· ·ÔÙÂϤÛÌ·Ù· ‰È·ÈÛÙÒıËÎ·Ó Û ̛· ÌÂϤÙË ·fi ÙËÓ ∞ã ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ (11), fiÔ˘ ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ‰Â‰Ô̤ӷ ·fi ÙË ¯ÔÚ‹ÁËÛË GH Û 156 ·È‰È¿ Ì GHD (62,2% Ì IGHD Î·È 35,2% Ì OGHD) ηٿ ÙËÓ ÂÚ›Ô‰Ô 1970-1997. ™Ù· ·È‰È¿ ·˘Ù¿, Ô ∂ƒ∞ ÚÔ ·ÁˆÁ‹˜ ‹Ù·Ó 3,8±1,3 cm/¯ÚfiÓÔ ÁÈ· ÙËÓ ÔÌ¿‰· Ì IGHD Î·È 4,0±3,0 cm/¯ÚfiÓÔ ÁÈ· ÂΛӷ Ì OGHD. ∫·Ù¿ ÙÔÓ 1Ô ¯ÚfiÓÔ ·ÁˆÁ‹˜, Ô ∂ƒ∞ ‹Ù·Ó 8,8±3,5 Î·È 8,2±4,0 cm/¯ÚfiÓÔ (p=NS) ÁÈ· ÙȘ ÔÌ¿‰Â˜ Ì ÌÂÌÔӈ̤ÓË IGHD Î·È ÔÏÏ·Ï‹ ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ·, ·ÓÙ›ÛÙÔȯ· (11). ∂›Û˘, Ô ∂ƒ∞ ·ÚÔ˘Û›·˙ ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ÙË ¯ÚÔÓÔÏÔÁÈ΋ (r=-0,53, p=0,001) Î·È ÔÛÙÈ΋ ËÏÈΛ· ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜ (r=-0,51, p=0,001) Î·È ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· (∆∞) (r=0,49, p=0,01) ÌfiÓÔ ÁÈ· ÙËÓ ÔÌ¿‰· Ì ÙËÓ ÔÏÏ·Ï‹ ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ·. ™˘ÓÂÒ˜, ÛËÌ·ÓÙÈ΋ ·Ú¿ÌÂÙÚÔ˜ ÁÈ· ÙËÓ ·Ú¯È΋ ÂÎÙ›ÌËÛË Ù˘ ·¿ÓÙËÛ˘ ÛÙËÓ ·ÁˆÁ‹ Ì rhGH Â›Ó·È Ë ·‡ÍËÛË ÙÔ˘ ∂ƒ∞ ηٿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ·ÁˆÁ‹˜, Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ˆ˜ Ê·ÈÓfiÌÂÓÔ “catch up” (·Ó·Ù˘ÍÈ·Îfi ¿ÏÌ·). √ ∂ƒ∞ ηٿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ·ÁˆÁ‹˜ ‰ÂÓ ·ÔÙÂÏ› ÚÔÁÓˆÛÙÈÎfi ‰Â›ÎÙË ÙÔ˘ ∆∞, ·ÏÏ¿ Ì›· ηϋ ·Ú¯È΋ ·¿ÓÙËÛË ÛÙËÓ ·ÁˆÁ‹ Ì rhGH Ô˘ ˘Ô‰ËÏÒÓÂÈ ÈηÓÔÔÈËÙÈÎfi ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· Ù˘ ·ÁˆÁ‹˜ (18). H ·¿ÓÙËÛË ÛÙËÓ Â͈ÁÂÓ‹ ¯ÔÚ‹ÁËÛË rhGH ÔÈΛÏÏÂÈ ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· (ÌÂÁ·Ï‡ÙÂÚË ·‡ÍËÛË Û ÌÈÎÚfiÙÂÚ· ·È‰È¿), ÙÔ ‚¿ÚÔ˜ ÛÒÌ·ÙÔ˜, ÙËÓ ÔÛfiÙËÙ· Î·È ÙÔ Â›‰Ô˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, fiˆ˜ ˘ÔÏÔÁ›˙ÂÙ·È ·fi Ù· ›‰· ÙˆÓ ‰ÂÛÌ¢ÙÈÎÒÓ ÚˆÙÂ˚ÓÒÓ Ù˘ GH (GH binding proteins, GHBPs), ηıÒ˜ ›Û˘ Î·È ·fi ÙËÓ ÂÔ¯‹ ÙÔ˘ ¤ÙÔ˘˜ (·˘ÍË̤ÓÔ˜ ÌÂÙ·‚ÔÏÈÛÌfi˜ ÙˆÓ ÔÛÙÒÓ Î·Ù¿ ÙËÓ ¿ÓÔÈÍË Î·È ÙÔ Î·ÏÔη›ÚÈ) (19,20). ªÈ· ¿ÏÏË ·Ú¿ÌÂÙÚÔ˜ Ô˘ ÂËÚ¿˙ÂÈ ÙËÓ ·ÓÙ·fiÎÚÈÛË ÛÙËÓ ·ÁˆÁ‹ Ì rhGH Û ·È‰È¿ Ì IGHD Â›Ó·È Ë ‚·Ú‡ÙËÙ· Ù˘ ·Ó¿ÚÎÂÈ·˜ Ù˘ GH (Ï‹Ú˘ ‹ ÌÂÚÈ΋ ·Ó¿ÚÎÂÈ·). ¶ÚÈÓ ·fi ÙËÓ ·ÁˆÁ‹, Ô ∂ƒ∞ ‰ÂÓ ‰È·Ê¤ÚÂÈ ¶·È‰È·ÙÚÈ΋ 2009;72:1-9
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·4
4
∫˘Úȷ΋ ∫·Ú·‚·Ó¿ÎË-∫·Ú·Ó¿ÛÈÔ˘
ÛËÌ·ÓÙÈο ÛÙȘ ÔÌ¿‰Â˜ Ì ÛÔ‚·Ú‹ ‹ ÌÂÚÈ΋ ·Ó¿ÚÎÂÈ· GH Î·È Â›Ó·È ÁÂÓÈο ¯·ÌËÏfi˜ (<50Ë ∂£ ÁÈ· ÙËÓ ËÏÈΛ·). ŸÌˆ˜, ÚÔÂÊË‚Èο, Ë ·‡ÍËÛË Î·Ù¿ Ù· 3 ÚÒÙ· ¯ÚfiÓÈ· ·ÁˆÁ‹˜ Ì rhGH Â›Ó·È ·Ó¿ÏÔÁË Ù˘ ‚·Ú‡ÙËÙ·˜ Ù˘ ·Ó¿ÚÎÂÈ·˜ GH. ∫·Ù¿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ·ÁˆÁ‹˜, Ù· ·È‰È¿ Ì ÛÔ‚·Ú‹ ·Ó¿ÚÎÂÈ· GH (<5 ng/ml) ¤¯Ô˘Ó ÛËÌ·ÓÙÈο ηχÙÂÚË ·ÓÙ·fiÎÚÈÛË ÛÙËÓ ·ÁˆÁ‹ (cm/¯ÚfiÓÔ), Û˘ÁÎÚÈÙÈο Ì ÙȘ ¿ÏϘ ÔÌ¿‰Â˜ (14). ∫·Ù¿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ·ÁˆÁ‹˜, Â¿Ó Ô ∂ƒ∞ Â›Ó·È >97 ∂£ ∂ƒ∞ ÁÈ· ÙËÓ ËÏÈΛ· Î·È ÙÔ Ê‡ÏÔ (‹ ¢SDS ‡„Ô˘˜ >0,5), Ë ·ÓÙ·fiÎÚÈÛË ıˆÚÂ›Ù·È ÈηÓÔÔÈËÙÈ΋ (14). ∏ ÔÚ›· ÙˆÓ SDS ‡„Ô˘˜ ηٿ Ù· 5 ÚÒÙ· ¯ÚfiÓÈ· ·ÁˆÁ‹˜ Ì rhGH ·ÚÔ˘ÛÈ¿˙ÂÈ ÛÙ·‰È·Î‹ ‚ÂÏÙ›ˆÛË. ŒÙÛÈ, ·fi Ì›· ÌÂϤÙË Ù˘ ∞ã ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ (∞ã ¶¶∫) (11) ‰È·ÈÛÙÒÓÂÙ·È ÌÈ· ÚÔԉ¢ÙÈ΋ ‚ÂÏÙ›ˆÛË ÙˆÓ SDS ‡„Ô˘˜ Ì ÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ, ·fi -2,9 SDS Úo ·ÁˆÁ‹˜ Û -2,4, -2,17 Î·È -1,9 ηٿ Ù· ÚÒÙ· 3 ¯ÚfiÓÈ· ·ÁˆÁ‹˜, ·ÓÙ›ÛÙÔȯ·. ∏ SDS ÙÔ˘ ÙÂÏÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜ ‹Ù·Ó -1,38 Î·È ‰ÂÓ ‰È¤ÊÂÚ ÛËÌ·ÓÙÈο ·fi ÙËÓ SDS ÙÔ˘ ‡„Ô˘˜-ÛÙfi¯Ô˘. ∏ ÛËÌ·Û›· Ù˘ ¤ÁηÈÚ˘ ¤Ó·Ú͢ ·ÁˆÁ‹˜ ·fi ÌÈÎÚ‹ ËÏÈΛ· Ê·›ÓÂÙ·È ÛÙË ÌÂϤÙË ÙˆÓ Gluckman et al. (6), fiÔ˘ Û˘ÁÎÚ›ÓÂÙ·È Ë ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· Ì rhGH Û ‰‡Ô ÔÌ¿‰Â˜ ·È‰ÈÒÓ: ·. ÔÌ¿‰· ‚ÚÂÊÒÓ Ì ¤Ó·ÚÍË ·ÁˆÁ‹˜ Û ËÏÈΛ· 1,2±0,6 ¯ÚfiÓˆÓ (n=45), ‚. ÔÌ¿‰· ·È‰ÈÒÓ Ì ¤Ó·ÚÍË ·ÁˆÁ‹˜ Û ËÏÈΛ· 7,5±0,3 ¯ÚfiÓˆÓ (n=42) (6). ∏ ·ÓÙ·fiÎÚÈÛË ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ·ÁˆÁ‹˜ ‹Ù·Ó ÛËÌ·ÓÙÈÎfiÙÂÚË ÛÙËÓ ÔÌ¿‰· ÙˆÓ ‚ÚÂÊÒÓ Ì ·‡ÍËÛË Ù˘ SDS ‡„Ô˘˜ ηٿ 1,6 SDS, Û˘ÁÎÚÈÙÈο Ì ÌfiÓÔ 0,5 SDS ÁÈ· ÙËÓ ÔÌ¿‰· ÙˆÓ ·È‰ÈÒÓ. ∞˘Ùfi ÌÔÚ› Ó· ·Ô‰Ôı› ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ù· ‚Ú¤ÊË ‹Ù·Ó ÛËÌ·ÓÙÈο ¯·ÌËÏfiÙÂÚÔ˘ ·Ó·ÛÙ‹Ì·ÙÔ˜ ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜ (-3,7 SDS), Û˘ÁÎÚÈÙÈο Ì ٷ ·È‰È¿ (-2,8 SDS). ∂›Û˘, Ë ÔÌ¿‰· ÙˆÓ ‚ÚÂÊÒÓ Â›¯Â ÛÔ‚·ÚfiÙÂÚË ·Ó¿ÚÎÂÈ· GH Û˘ÁÎÚÈÙÈο Ì ٷ ·È‰È¿. ∏ ·¿ÓÙËÛË ÙˆÓ ‚ÚÂÊÒÓ Î·Ù¿ Ù· ÂfiÌÂÓ· 4 ¯ÚfiÓÈ· ·ÁˆÁ‹˜ ‹Ù·Ó ›Û˘ ηχÙÂÚË ·fi ÂΛÓË ÙˆÓ ·È‰ÈÒÓ (6). ∞Ó¿ÏÔÁ· ·ÔÙÂϤÛÌ·Ù· ·Ó·Ê¤ÚÔÓÙ·È ÛÙË ÌÂϤÙË ÙˆÓ Ranke et al (8). ∂›Û˘, Û ÌÈ· ÔÌ¿‰· ·È‰ÈÒÓ Ì ¤Ó·ÚÍË ·ÁˆÁ‹˜ Û ËÏÈΛ· 5,8±3,8 ÌËÓÒÓ, ÔÈ ·ÛıÂÓ›˜ ¤Êı·Û·Ó ÌÂÙ¿ ·ÁˆÁ‹ ÁÈ· 8 ¤ÙË Û ·Ó¿ÛÙËÌ· ˘„ËÏfiÙÂÚÔ ·fi ÙÔ ‡„Ô˜-ÛÙfi¯Ô, ÁÂÁÔÓfi˜ Ô˘ ˘ÔÁÚ·ÌÌ›˙ÂÈ ÙË ÛËÌ·Û›· Ù˘ ¤ÁηÈÚ˘ ¤Ó·Ú͢ ·ÁˆÁ‹˜ (21). µ) ∫·Ù¿ ÙËÓ ÂÊ˂›· ∆Ô ‡„Ô˜ Ô˘ ·ÔÎÙ‹ıËΠηٿ Ù· ÚÔÂÊË‚Èο ¯ÚfiÓÈ· ÛÙË ÌÂϤÙË KIGS ‹Ù·Ó ηٿ 1,5 ÊÔÚ¿ ÌÂÁ·Ï‡ÙÂÚÔ ÛÙËÓ ÔÌ¿‰· Ì ÚÔÎÏËÙ‹ ‹‚Ë (ÏfiÁˆ ·‰˘Ó·Ì›·˜ Ê˘ÛÈÔÏÔÁÈ΋˜ ÂÓ‹‚ˆÛ˘), Û˘ÁÎÚÈÙÈο Ì ÂΛÓË Ì ·˘ÙfiÌ·ÙË ‹‚Ë (22). ∆Ô ÁÂÁÔÓfi˜ ·˘Ùfi ·Ô‰fiıËΠPaediatriki 2009;72:1-9
ÛÙË ¯ÚÔÓÈ΋ ·Ú¿Ù·ÛË Î·Ù¿ 3,5-4,0 ¯ÚfiÓÈ· Ù˘ ‰È¿ÚÎÂÈ·˜ Ù˘ ¯ÔÚ‹ÁËÛ˘ rhGH ÛÙÔ ÚÔÂÊË‚ÈÎfi ÛÙ¿‰ÈÔ ÛÙËÓ ÔÌ¿‰· Ì ÙËÓ ÚÔÎÏËÙ‹ ‹‚Ë. ¶Ú¤ÂÈ fï˜ Ó· ÛËÌÂȈı› fiÙÈ Ë ÔÌ¿‰· Ì ÚÔÎÏËÙ‹ ‹‚Ë Â›¯Â ÌÈÎÚfiÙÂÚË ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ÂÊË‚È΋˜ ·Ó¿Ù˘Í˘ Î·È ÌÈÎÚfiÙÂÚË ·fiÎÙËÛË ‡„Ô˘˜ ηٿ ÙËÓ ÂÊ˂›· (p<0,001). ∏ ‰È·ÊÔÚ¿ ÙˆÓ SDS ÙÔ˘ ÙÂÏÈÎÔ‡-·Ú¯ÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜ ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚË ÛÙËÓ ÔÌ¿‰· Ì ÚÔÎÏËÙ‹ ‹‚Ë Û˘ÁÎÚÈÙÈο Ì ÂΛÓË Ì ·˘ÙfiÌ·ÙË ‹‚Ë (2,7 ¤Ó·ÓÙÈ 1,9, p<0,001). ∏ ηχÙÂÚË ·¿ÓÙËÛË ÛÙËÓ ÔÌ¿‰· Ì ÙËÓ ÚÔÎÏËÙ‹ ‹‚Ë ÔÊ›ÏÂÙ·È Èı·ÓfiÓ ÛÙÔ ¯·ÌËÏfiÙÂÚÔ ‡„Ô˜ ÚÔ ·ÁˆÁ‹˜ Î·È Û˘ÓÂÒ˜ ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ‰˘Ó·ÌÈÎfi ·‡ÍËÛ˘, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ÛÔ‚·ÚfiÙÂÚË ·Ó¿ÚÎÂÈ· GH (22). √ÌÔ›ˆ˜, ηٿ ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ÌÂϤÙ˘ Ù˘ ∞ã ¶¶∫ (11), fiÔ˘ Û˘ÁÎÚ›ÓÂÙ·È ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ÙˆÓ ·È‰ÈÒÓ Ì ÚÔÎÏËÙ‹ ‹ ·˘ÙfiÌ·ÙË ‹‚Ë, ‰È·ÈÛÙÒıËΠfiÙÈ Ë SDS ÙÔ˘ ∆∞ ÛÙ· ·È‰È¿ Ì ÚÔÎÏËÙ‹ ‹‚Ë ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚË ÂÎÂ›ÓˆÓ Ì ·˘ÙfiÌ·ÙË ‹‚Ë (-1,04 ¤Ó·ÓÙÈ -1,7, p=0,001). ∆Ô ÁÂÁÔÓfi˜ ·˘Ùfi ·Ô‰›‰ÂÙ·È ÛÙÔ fiÙÈ Ù· ·È‰È¿ Ì ÚÔÎÏËÙ‹ ‹‚Ë ‹Ù·Ó ˘„ËÏfiÙÂÚ· ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ‹‚˘ Î·È ÛÙÔ fiÙÈ Ë ¤Ó·ÚÍË Ù˘ ‹‚˘ ¤ÁÈÓ Û ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ· ·fi fi,ÙÈ ÛÙ· ·È‰È¿ Ì ·˘ÙfiÌ·ÙË ‹‚Ë. ∂Âȉ‹ ÙÔ ∆∞ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ·Ó¿ÛÙËÌ· ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ‹‚˘ (17,22,23), Ú¤ÂÈ Ó· Á›ÓÂÈ ÚÔÛ¿ıÂÈ· Ó· ÂÈÙ¢¯ı› ·Ó¿ÛÙËÌ· ÂÓÙfi˜ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÔÚ›ˆÓ ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ‹‚˘. ∂›Û˘, ¤¯ÂÈ ‚ÚÂı› fiÙÈ ÙÔ ‡„Ô˜ Ô˘ ·ÔÎÙ¿Ù·È Î·Ù¿ ÙËÓ ÂÊ˂›· Û˘Û¯ÂÙ›˙ÂÙ·È ·ÚÓËÙÈο Ì ÙËÓ ËÏÈΛ· ¤Ó·Ú͢ Ù˘ ‹‚˘ ÙfiÛÔ ÛÙ· Ê˘ÛÈÔÏÔÁÈο ·È‰È¿ fiÛÔ Î·È Û ÂΛӷ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ·ÁˆÁ‹ Ì rhGH (24,25).
¶·Ú¿ÌÂÙÚÔÈ Ô˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ·‡ÍËÛË Î·Ù¿ ÙËÓ ÂÊ˂›· 1. A˘ÍË̤ÓË ‰fiÛË rhGH ηٿ ÙËÓ ÂÊ˂›· ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ë ¤ÎÎÚÈÛË GH ·˘Í¿ÓÂÙ·È ÛÙ· Ê˘ÛÈÔÏÔÁÈο ·È‰È¿ ηٿ 2 Ì 4 ÊÔÚ¤˜ ηٿ ÙËÓ ÂÊ˂›·, Ì ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙˆÓ ·˘ÍËÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ (IGF-1). ∏ ·Ú·Ù‹ÚËÛË ·˘Ù‹ Ô‰‹ÁËÛ ÛÙÔ ÂÚÒÙËÌ· Ì‹ˆ˜ Ë ¯Ú‹ÛË ˘„ËÏÒÓ ‰fiÛÂˆÓ rhGH ηٿ ÙËÓ ÂÊ˂›· ı· Û˘Ó¤‚·ÏÏ ÛÙË ‚ÂÏÙ›ˆÛË ÙÔ˘ ∆∞. ™Â ÌÈ· ÌÂϤÙË ‰È·ÈÛÙÒıËΠfiÙÈ Ë ‰ÔÛÔÏÔÁ›· rhGH 30 IU/m2/‚‰ÔÌ¿‰· ÛÙËÓ ÂÊ˂›·, Û˘ÁÎÚÈÙÈο Ì 15 IU/m2/‚‰ÔÌ¿‰· (0,28 ¤Ó·ÓÙÈ 0,14 mg/kg/Ë̤ڷ), ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÌÈÎÚ‹ ‚ÂÏÙ›ˆÛË ÛÙÔ ∆∞ (3 cm) (26,27). ∞ÓÙ›ıÂÙ·, Ë ¯Ú‹ÛË ˘„ËÏÒÓ ‰fiÛÂˆÓ rhGH (0,7 mg/kg/‚‰ÔÌ¿‰·), Û˘ÁÎÚÈÙÈο Ì 0,28 mg/kg/‚‰ÔÌ¿‰·, ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÛÙËÓ SDS ÙÔ˘ ∆∞ (0,0 ¤Ó·ÓÙÈ -0,7, ·ÓÙ›ÛÙÔȯ·) (27). µÚ¤ıËΠfiÙÈ Ë ÌÂÁ·Ï‡ÙÂÚË ‰fiÛË ‰ÂÓ ÂÈÙ¿¯˘Ó ˘¤ÚÌÂÙÚ· ÙËÓ ÔÛÙÈ΋ ˆÚ›Ì·ÓÛË (‰È·ÊÔÚ¿ ÔÛÙÈ΋˜ ËÏÈΛ·˜ 3,0 ¤Ó·ÓÙÈ 3,2 ÂÙÒÓ Û ‰È¿ÛÙËÌ· 3
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·5
5
¶·È‰È¿ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘
¶›Ó·Î·˜ 3. ∆ÂÏÈÎfi ·Ó¿ÛÙËÌ· ·È‰ÈÒÓ Ì IGHD ˘fi ·ÁˆÁ‹ Ì rhGH ªÂϤÙË ∫πGS ¡CGS
º‡ÏÔ
n
¢fiÛË rhGH (mg/kg/‚‰)
¢È¿ÚÎÂÈ· ·ÁˆÁ‹˜ (¤ÙË)
SDS TA
SDS ∆∞-À™
∞ £ ∞ £
792 466 2.095 1.116
0,18 0,18 0,28 0,29
8,1 7,9 5,2 5,0
-1,0 -1,3 -1,1 -1,3
-0,2 -0,5 -0,7 -0,9
TA = ∆ÂÏÈÎfi ·Ó¿ÛÙËÌ·, À™ = ⁄„Ô˜ ÛÙfi¯Ô˜, ∞ = ÕÚÚÂÓ, £ = £‹Ï˘
¯ÚfiÓˆÓ ıÂڷ›·˜ ÁÈ· ÙȘ ÔÌ¿‰Â˜ Ì ÙË ÌÂÁ·Ï‡ÙÂÚË Î·È ÙË ÌÈÎÚfiÙÂÚË ‰fiÛË, ·ÓÙ›ÛÙÔȯ·) Î·È ‰ÂÓ Â›¯Â ÛËÌ·ÓÙÈΤ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ (ÂÎÙfi˜ ·fi ÙËÓ ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ÙÔ˘ IGF1). ŸÌˆ˜, ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙÔ˘ ÎfiÛÙÔ˘˜ ıÂڷ›·˜. ∏ ¯ÔÚ‹ÁËÛË ˘„ËÏÒÓ ‰fiÛÂˆÓ rhGH ¯ÔÚËÁÂ›Ù·È Û ÂÈÏÂÁ̤Ó˜ ÂÚÈÙÒÛÂȘ Î·È ¤Ó‰ÂÈÍË ·ÔÙÂÏ› ÙÔ ¯·ÌËÏfi ·Ó¿ÛÙËÌ· ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ‹‚˘. 2. ∞Ó·ÛÙÔÏ‹ Ù˘ ÂÊË‚È΋˜ ·Ó¿Ù˘Í˘ (¯Ú‹ÛË ·Ó·ÏfiÁˆÓ Ù˘ Gonadotropin Releasing Hormone) H ¯Ú‹ÛË GnRH analogs (GnRH-an) Û ·È‰È¿ Ì ÚfiˆÚË ‹‚Ë ·Ô‰Â›¯ıËΠfiÙÈ ‚ÂÏÙÈÒÓÂÈ ÛËÌ·ÓÙÈο ÙÔ ∆∞ (28). º·›ÓÂÙ·È, fï˜, fiÙÈ Û ·È‰È¿ Ì IGHD, Ë ·ÁˆÁ‹ ·˘Ù‹ ÛÂ Û˘Ó‰˘·ÛÌfi Ì rhGH Ô‰ËÁ› Û ÛËÌ·ÓÙÈ΋ ‚ÂÏÙ›ˆÛË ÙÔ˘ ÚÔ‚ÏÂfiÌÂÓÔ˘ ∆∞. ŒÙÛÈ, Û ÌÈ· ÌÂϤÙË ·fi ÙÔ˘˜ Mericq et al. (29) Û 21 ·È‰È¿ Ì ·Ó¿ÚÎÂÈ· GH, ·Ó·Ê¤ÚÂÙ·È fiÙÈ ÙÔ ÚÔ‚ÏÂfiÌÂÓÔ ∆∞ ÛÙËÓ ÔÌ¿‰· Ô˘ ¤Ï·‚Â Û˘Ó‰˘·ÛÌfi GH Î·È GnRH-an ÁÈ· 3 ¤ÙË ‹Ù·Ó -1,3±0,5 SD, ÂÓÒ ÛÙËÓ ÔÌ¿‰· Ô˘ ¤Ï·‚ ÌfiÓÔ GH ‹Ù·Ó -2,7±0,3 SD (26). ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿ ‰ÂÓ ÂȂ‚·ÈÒÓÔÓÙ·È ·fi ÙȘ ÌÂÁ¿Ï˜ ÔÏ˘ÎÂÓÙÚÈΤ˜ ÌÂϤÙ˜ KIGS (30) Î·È NCGS (31). ÃÚÂÈ¿˙ÔÓÙ·È ÂÚÈÛÛfiÙÂÚ˜ ÚÔÔÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ÙËÓ ÂȂ‚·›ˆÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ·˘ÙÒÓ. ∏ ·ÓˆÙ¤Úˆ ·ÁˆÁ‹ ·Â˘ı‡ÓÂÙ·È Î˘Ú›ˆ˜ Û ·È‰È¿ Ì ÚÔ¯ˆÚË̤ÓË ‹ Ù·¯¤ˆ˜ ÂÍÂÏÈÛÛfiÌÂÓË ‹‚Ë.
∆ÂÏÈÎfi ·Ó¿ÛÙËÌ· ∞fi ÙËÓ ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË KIGS, Ë ÔÔ›· Â›Ó·È ÌÈ· ÌÂÁ¿ÏË ÂȉËÌÈÔÏÔÁÈ΋ ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ Î·È ÂÚÈÏ·Ì‚¿ÓÂÈ 3.966 ·ÛıÂÓ›˜ Ì GHD ·fi ‰È¿ÊÔÚ˜ ¯ÒÚ˜, ‰È·ÈÛÙÒıËÎ·Ó ‰È·ÊÔÚ¤˜ ÛÙÔ ıÂڷ¢ÙÈÎfi ·ÔÙ¤ÏÂÛÌ· ·ÁˆÁ‹˜ Ì rhGH Û ·È‰È¿ Ì IGHD ·Ó¿ÏÔÁ· Ì ÙË Ê˘Ï‹, ÙÔ Ê‡ÏÔ, ηıÒ˜ Î·È ÙËÓ ·ÚÔ˘Û›· ÌÂÌÔӈ̤Ó˘ IGHD ‹ ÔÏÏ·Ï‹˜ ˘ÔÊ˘Ûȷ΋˜ ·Ó¿ÚÎÂÈ·˜ (22). To TA ·ÛıÂÓÒÓ Ì IGHD ˘fi ·ÁˆÁ‹ Ì rhGH ¤¯ÂÈ ·ÚÔ˘ÛÈ¿ÛÂÈ ÛÙ·‰È·Î‹ ‚ÂÏÙ›ˆÛË Ì ÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ. ŒÙÛÈ, ·fi ÙËÓ ·Ó·‰ÚÔÌÈ΋ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ÌÂϤÙ˘ Ù˘ ∞ã ¶¶∫ (11) ÁÈ· Ù· ¯ÚfiÓÈ· 1970 ˆ˜ 1997 (¶›Ó·Î·˜ 3), ‰È·ÈÛÙÒıËΠfiÙÈ Ì ÙËÓ ÚÔԉ¢ÙÈ΋ ·‡ÍËÛË Ù˘ ‰fiÛ˘ Ù˘ GH (·fi
0,4 Û 0,6 IU/kg/‚‰ÔÌ¿‰·) Î·È ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÂÓ¤ÛˆÓ/‚‰ÔÌ¿‰· (·fi 3,5 Û 6,4/‚‰ÔÌ¿‰·), ÙÔ ∆∞ ‚ÂÏÙÈÒıËΠÛÙ·‰È·Î¿ ·fi -3,9 Û -2,4 SDS. ¢Â‰Ô̤ӷ ·fi ÙȘ ‰‡Ô ÌÂÁ·Ï‡ÙÂÚ˜ ÔÏ˘ÎÂÓÙÚÈΤ˜ ÌÂϤÙ˜ Ô˘ ÂÎÚÔÛˆÔ‡Ó ÙËÓ Â˘Úˆ·˚΋ (KIGS) (27) Î·È ÙËÓ ·ÌÂÚÈηÓÈ΋ ÂÌÂÈÚ›· (NCGS) (32) Ê·›ÓÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 3. ∞fi ÙȘ Ì·ÎÚÔ¯ÚfiÓȘ ·˘Ù¤˜ ÌÂϤÙ˜ ·Ô‰ÂÈÎÓ‡ÂÙ·È fiÙÈ ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ·ÛıÂÓ›˜ ‰ÂÓ Êı¿ÓÔ˘Ó ÛÙÔ ÎÏËÚÔÓÔÌÈο ÚÔ‚ÏÂfiÌÂÓÔ ∆∞. AÓ¿ÏÔÁ· ·ÔÙÂϤÛÌ·Ù· Ì ÙȘ ÌÂϤÙ˜ KIGS Î·È NCGS ·Ó·Ê¤ÚÔÓÙ·È ÛÙË ÌÂϤÙË Ù˘ ∞ã ¶¶∫ (11), fiÔ˘ Û 116 ·È‰È¿ Ì IGHD Ô˘ ¤Ï·‚·Ó ·ÁˆÁ‹ Ì rhGH ÌÂÙ¿ ÙÔ 1986 Û ‰fiÛË 0,15-0,18 mg/kg/‚‰ÔÌ¿‰·, ‰È·ÈÛÙÒıËΠfiÙÈ Ë SDS TA ‹Ù·Ó -1,3, ÂÓÒ Ë ‰È·ÊÔÚ¿ ÙˆÓ SDS ÙÂÏÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜ Î·È ‡„Ô˘˜-ÛÙfi¯Ô˘ ‹Ù·Ó -0,28. ªÈ· ÛԢˉÈ΋ ÌÂϤÙË ¤‰ÂÈÍ fiÙÈ Â›Ó·È ‰˘Ó·Ù‹ Ë Â›Ù¢ÍË ÂÓfi˜ SDS TA -0,3, Ô˘ Â›Ó·È ·Ó¿ÏÔÁË ÙÔ˘ ‡„Ô˘˜-ÛÙfi¯Ô˘ (33). ∆· ÎÚÈÙ‹ÚÈ· ÁÈ· ÙË ‰È·ÎÔ‹ Ù˘ ·ÁˆÁ‹˜ Ì rhGH ‰ÂÓ Â›Ó·È ÛÙ·ıÂÚ¿ Î·È ÔÈΛÏÏÔ˘Ó ÛÙȘ ‰È¿ÊÔÚ˜ ¯ÒÚ˜. ŒÙÛÈ, Û οÔȘ ¯ÒÚ˜ ‰È·ÎfiÙÂÙ·È Ë ·ÁˆÁ‹ fiÙ·Ó ÙÔ ·Ó¿ÛÙËÌ· Êı¿ÛÂÈ ÂÓÙfi˜ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÔÚ›ˆÓ ÁÈ· ÙËÓ ËÏÈΛ· Î·È ÙÔ Ê‡ÏÔ, ÂÓÒ Û ¿ÏϘ ¯ÒÚ˜ Ë ·ÁˆÁ‹ Ì rhGH Û˘Ó¯›˙ÂÙ·È Ì¤¯ÚÈ Ó· ÂÈÙ¢¯ı› ∆∞ Î·È Î·ÙfiÈÓ Û˘Ó¯›˙ÂÙ·È Ì ¯·ÌËÏfiÙÂÚ˜ ‰fiÛÂȘ, ˆ˜ ıÂڷ›· ˘ÔηٿÛÙ·Û˘, ÛÙËÓ ÂÓ‹ÏÈÎË ˙ˆ‹ (22). ™ÙË ÌÂϤÙË ∫IGS ‰È·ÈÛÙÒıËΠfiÙÈ Û 22% ÙˆÓ ·ÛıÂÓÒÓ Ë ·ÁˆÁ‹ Ì rhGH ‰È·ÎfiËΠÚÈÓ ÙËÓ Â›Ù¢ÍË ÙÔ˘ ∆∞ (34). ™Â Ì›· ¿ÏÏË ÌÂϤÙË ·Ó·Ê¤ÚÂÙ·È fiÙÈ 50% ÙˆÓ ·ÛıÂÓÒÓ ‰ÂÓ ¤¯Ô˘Ó Ï‹ÚË Û˘ÌÌfiÚʈÛË Ì ÙËÓ ·ÁˆÁ‹ Î·È Ë Û˘¯Ó‹ ·Ú¿ÏË„Ë ÙˆÓ ‰fiÛÂˆÓ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ì›ˆÛË ÙÔ˘ ∂ƒ∞ Î·È ¯·ÌËÏfiÙÂÚÔ ∆∞ (35). ™ÙÔÓ ¶›Ó·Î· 4 ·Ó·Ê¤ÚÔÓÙ·È Ù· Û˘Ó‹ıË ·›ÙÈ· ÁÈ· ÙË ÌÂȈ̤ÓË ·¿ÓÙËÛË ÛÙËÓ ·ÁˆÁ‹ Ì rhGH Û ·È‰È¿ Ì GHD (13). ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜ Û˘ÓÈÛÙ¿Ù·È Ó· ÂÍÂÙ·Ûı› ΢ڛˆ˜ ÙÔ ÂӉ¯fiÌÂÓÔ ÂÏ·Ùو̤Ó˘ Û˘ÌÌfiÚʈÛ˘ Ì ÙËÓ ·ÁˆÁ‹. ªÂÙ¿ ÙËÓ ÔÏÔÎÏ‹ÚˆÛË Ù˘ ıÂڷ›·˜ Î·È ÙËÓ ·fiÎÙËÛË ÙÔ˘ ÙÂÏÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜, Â›Ó·È ··Ú·›ÙËÙÔ Ó· Á›ÓÂÈ Â·Ó¤ÏÂÁ¯Ô˜ Ì ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘ GH, Û ‰È¿ÛÙËÌ· 6 ÌËÓÒÓ ÌÂÙ¿ ÙË ‰È·ÎÔ‹ Ù˘ rhGH. ∆Ô ÔÛÔÛÙfi ·Ú·ÌÔÓ‹˜ Ù˘ ·Ó¿ÚÎÂÈ·˜ GH ¶·È‰È·ÙÚÈ΋ 2009;72:1-9
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·6
6
∫˘Úȷ΋ ∫·Ú·‚·Ó¿ÎË-∫·Ú·Ó¿ÛÈÔ˘
¶›Ó·Î·˜ 4. ∞›ÙÈ· ÌÂȈ̤Ó˘ ·ÓÙ·fiÎÚÈÛ˘ ÛÙËÓ ·ÁˆÁ‹ Ì rhGH Û ·È‰È¿ Ì GHD 1. ªË Û˘ÌÌfiÚʈÛË Ì ÙËÓ ·ÁˆÁ‹ 2. ∞Ó·Ú΋˜ ÚÔÂÙÔÈÌ·Û›· Î·È ·Ôı‹Î¢ÛË Ù˘ rhGH 3. §·Óı·Ṳ̂ÓË Ù¯ÓÈ΋ ¯ÔÚ‹ÁËÛ˘ ÙˆÓ ÂÓ¤ÛÂˆÓ 4. ¶ÚfiÁÚ·ÌÌ· ¯ÔÚ‹ÁËÛ˘ rhGH 5. À¤ÚÌÂÙÚË ‰fiÛË ÁÏ˘ÎÔÎÔÚÙÈÎÔÂȉÒÓ Û ·È‰È¿ ÌÂ Û˘Ó˘¿Ú¯Ô˘Û· ·Ó¿ÚÎÂÈ· ACTH 6. YÔı˘ÚÂÔÂȉÈÛÌfi˜ Ô˘ ‰ÂÓ ·ÓÙÈÌÂÙˆ›ÛÙËΠ7. ∞Ó·Ú΋˜ ‰È·ÙÚÔÊ‹ 8. ™˘¯Ó¤˜ ÏÔÈÌÒÍÂȘ 9. ∞ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ rhGH 10. πÛÙÔÚÈÎfi ·ÎÙÈÓÔ‚ÔÏ›·˜ Ù˘ ÛÔÓ‰˘ÏÈ΋˜ ÛÙ‹Ï˘ 11. æ˘¯ÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ 12. §·Óı·Ṳ̂ÓË ‰È¿ÁÓˆÛË
ÔÈΛÏÏÂÈ. ŒÙÛÈ, ÔÈ Tauber Î·È Û˘Ó. (36) ·Ó·Ê¤ÚÔ˘Ó fiÙÈ, ·fi Ù· ·È‰È¿ Ì ÌÂÚÈ΋ ·Ó¿ÚÎÂÈ· GH ÛÙȘ ·Ú¯ÈΤ˜ ‰˘Ó·ÌÈΤ˜ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘ GH, 71% ›¯·Ó Ê˘ÛÈÔÏÔÁÈ΋ ·¿ÓÙËÛË Î·Ù¿ ÙÔÓ Â·Ó¤ÏÂÁ¯Ô. ∞ÓÙ›ıÂÙ·, ÌfiÓÔ 36% ÙˆÓ ·È‰ÈÒÓ Ì ϋÚË ·Ó¿ÚÎÂÈ· GH Î·È 3% ÙˆÓ ·È‰ÈÒÓ Ì ÔÏÏ·Ï‹ ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ· ›¯·Ó Ê˘ÛÈÔÏÔÁÈ΋ ·¿ÓÙËÛË GH ηٿ ÙÔÓ Â·Ó¤ÏÂÁ¯Ô (37). ™Â ÂÚ›ÙˆÛË Ô˘ ı· ‰È·ÈÛÙˆı› ·Ó¿ÚÎÂÈ· GH ηٿ ÙÔÓ Â·Ó¤ÏÂÁ¯Ô, ¯ÚÂÈ¿˙ÂÙ·È Ó· Û˘Ó¯ÈÛı› Ë ıÂڷ›· Ì rhGH. ∏ ¯ÔÚ‹ÁËÛË rhGH Û ÂÓ‹ÏÈΘ Ì ·Ó¿ÚÎÂÈ· GH ¤¯ÂÈ Û˘˙ËÙËı› ·ÚÎÂÙ¿ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·, ÏfiÁˆ ÙˆÓ ÚÔ‚ÏËÌ¿ÙˆÓ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜. ∏ ¤ÏÏÂÈ„Ë GH ÛÙÔ˘˜ ÂÓ‹ÏÈΘ Ô‰ËÁ› Û ‰È·Ù·Ú·¯¤˜ ÛÙË ÛˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË (ÎÂÓÙÚÈ΋ ·¯˘Û·ÚΛ·, ÂÏ·Ùو̤ÓË ¿ÏÈÔ˜ Ì¿˙·) Î·È ÛÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÔÛÙÒÓ (ÂÏ·Ùو̤ÓË ÔÛÙÈ΋ ˘ÎÓfiÙËÙ·, ÔÛÙÂÔfiÚˆÛË). ∂›Û˘ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ηډȷÁÁÂȷο ÂÂÈÛfi‰È· ÏfiÁˆ ˘ÂÚ¯ÔÏËÛÙÂÚÔÏ·ÈÌ›·˜, ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·˜ Î·È ÂÈÙ¿¯˘ÓÛ˘ Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ (38,39,40). ∂ÈÚfiÛıÂÙ·, Ô‰ËÁ› Û ¯·ÌËÏfiÙÂÚË ÔÈfiÙËÙ· ˙ˆ‹˜, ÏfiÁˆ ηٷ‚ÔÏ‹˜, ÌÂȈ̤Ó˘ ÂÓÂÚÁËÙÈÎfiÙËÙ·˜ Î·È ÌÂȈ̤Ó˘ ¢ÂÍ›·˜ (41). ∞ÓÙ›ıÂÙ·, Ë ¯ÔÚ‹ÁËÛË rhGH ¤¯ÂÈ ‰È·ÈÛÙˆı› fiÙÈ ‚ÂÏÙÈÒÓÂÈ ÙË ÛˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË Î·È ÙËÓ ÔÈfiÙËÙ· ˙ˆ‹˜ ÛÙÔ˘˜ ÂÚÈÛÛfiÙÂÚÔ˘˜ ·ÛıÂÓ›˜ (42). ŒÙÛÈ, Ë ¯Ú‹ÛË Ù˘ rhGH Û ÌÂȈ̤ÓË ‰fiÛË ÛÙËÓ ÂÓ‹ÏÈÎÔ ˙ˆ‹ ¤¯ÂÈ ·Ú¯›ÛÂÈ Ó· ¯ÔÚËÁÂ›Ù·È Û ÔÚÈṲ̂Ó˜ ¯ÒÚ˜ ÁÈ· ÙËÓ ÚfiÏË„Ë ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ Î·È „˘¯ÔÎÔÈÓˆÓÈÎÒÓ ÂÈÙÒÛÂˆÓ Ù˘ ·Ó¿ÚÎÂÈ·˜ GH.
¶·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· Afi ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙÔ ∆∞ ·È‰ÈÒÓ Ì ȉÈÔ·ı‹ ‹ ÔÚÁ·ÓÈ΋ GHD (¶›Ó·Î·˜ 5) ÛËÌ·ÓÙÈÎfiÙÂÚÔÈ Â›Ó·È ÙÔ ‡„Ô˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·ÁˆÁ‹˜ Ì rhGH, ηıÒ˜ Î·È ÙÔ ‡„Ô˜ ÛÒÌ·ÙÔ˜ ÁÔÓ¤ˆÓ (22). Paediatriki 2009;72:1-9
¶›Ó·Î·˜ 5. ¶·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ÌÂÙ¿ ·ÁˆÁ‹ Ì rhGH 1. ⁄„Ô˜ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·ÁˆÁ‹˜ Ì rhGH 2. ⁄„Ô˜ ÁÔÓ¤ˆÓ 3. ∏ÏÈΛ· ¤Ó·Ú͢ ·ÁˆÁ‹˜ Ì rhGH 4. ™˘ÓÔÏÈ΋ ‰È¿ÚÎÂÈ· ·ÁˆÁ‹˜ Ì rhGH 5. ∏ÏÈΛ· ¤Ó·Ú͢ Ù˘ ‹‚˘ 6. µ¿ÚÔ˜ Î·È Ì‹ÎÔ˜ ηٿ ÙËÓ Á¤ÓÓËÛË 7. ƒ˘ıÌfi˜ ·‡ÍËÛ˘ ηٿ ÙÔÓ 1Ô ¯ÚfiÓÔ ·ÁˆÁ‹˜ Ì rhGH 8. ¢ÔÛÔÏÔÁ›· rhGH
ÕÏϘ ·Ú¿ÌÂÙÚÔÈ Ô˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È ÛËÌ·ÓÙÈο Ì ÙÔ ∆∞ ηٿ ÙËÓ ·ÁˆÁ‹ Ì rhGH Î·È ·ÏÏËÏÂȉÚÔ‡Ó ÌÂٷ͇ ÙÔ˘˜ Â›Ó·È Ë ËÏÈΛ· ¤Ó·Ú͢ ·ÁˆÁ‹˜ Ì rhGH Î·È Ë Û˘ÓÔÏÈ΋ ‰È¿ÚÎÂÈ· ·ÁˆÁ‹˜, ȉȷ›ÙÂÚ· ηٿ ÙÔ ÚÔÂÊË‚ÈÎfi ÛÙ¿‰ÈÔ. ŒÙÛÈ, ¤Ó· ÌÈÎÚfiÙÂÚÔ ·È‰› ı· Ï¿‚ÂÈ ·ÁˆÁ‹ Ì rhGH ÁÈ· ÌÂÁ·Ï‡ÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Î·È ÙÂÏÈο ı· Ï¿‚ÂÈ Û˘ÓÔÏÈο ÌÂÁ·Ï‡ÙÂÚË ÔÛfiÙËÙ· rhGH ηÈ, ΢ڛˆ˜, ηٿ Ù· ϤÔÓ ·Ô‰ÔÙÈο ˆ˜ ÚÔ˜ ÙÔ ∆∞ ÚÔÂÊË‚Èο ¯ÚfiÓÈ· (13,34). ∂›Û˘, ÛËÌ·ÓÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ÙÔ ∆∞ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÙÔ ‡„Ô˜-ÛÙfi¯Ô˜, Ë SDS ‡„Ô˘˜ Î·È Ë ËÏÈΛ· ¤Ó·Ú͢ Ù˘ ‹‚˘, ÙÔ ‚¿ÚÔ˜ Î·È ÙÔ Ì‹ÎÔ˜ Á¤ÓÓËÛ˘ (13,43). √È Ì¤ÁÈÛÙ˜ ÙÈ̤˜ GH ηٿ ÙȘ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘, ˆ˜ ‰Â›ÎÙ˘ ÛÔ‚·ÚfiÙËÙ·˜ Ù˘ IGHD, ‰ÂÓ Ê·›ÓÂÙ·È Ó· ÂËÚ¿˙Ô˘Ó ÙÔ ∆∞ (13,22). ŒÓ·˜ ¿ÏÏÔ˜ ·Ú¿ÁÔÓÙ·˜ Ô˘ ÂËÚ¿˙ÂÈ ÙÔ ∆∞ Â›Ó·È Ë ‰fiÛË Ù˘ rhGH. ∂›Ó·È fï˜ ·ÍÈÔÛËÌ›ˆÙÔ fiÙÈ Û ·È‰È¿ Ì IGHD, Ë Û˘Ì‚·ÙÈ΋ ‰ÔÛÔÏÔÁ›· rhGH (0,18-0,3 mg/kg/‚‰ÔÌ¿‰·) Ô‰ËÁ› Û ∆∞ ¯·ÌËÏfiÙÂÚÔ ÙÔ˘ ‡„Ô˘˜-ÛÙfi¯Ô˘ (À™) (44,45), ÂÓÒ Ë ¯Ú‹ÛË ˘„ËÏÒÓ ‰fiÛÂˆÓ rhGH (0,7 mg/kg/‚‰ÔÌ¿‰·) (27) ‹ Ë ÂÓˆÚ›˜ ‰È¿ÁÓˆÛË Ù˘ GHD Î·È ¤Ó·ÚÍË ·ÁˆÁ‹˜ Ô‰ËÁÔ‡Ó ÛÙËÓ Â›Ù¢ÍË ÂÓfi˜ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ∆∞ Ô˘ ‰ÂÓ ‰È·Ê¤ÚÂÈ ·fi ÙÔ À™. §·Ì‚¿ÓÔÓÙ·˜, fï˜, ˘’fi„ÈÓ ÙÔ ˘„ËÏfi ÎfiÛÙÔ˜ Î·È ÙȘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Ù˘ ˘„ËÏ‹˜ ‰ÔÛÔÏÔÁ›·˜ rhGH, Ë ıÂڷ›· Ú¤ÂÈ Ó· ÂÍ·ÙÔÌÈ·ÂÙ·È Î·È Ë ¯Ú‹ÛË ˘„ËÏÒÓ ‰fiÛÂˆÓ Ó· ÂÚÈÔÚ›˙ÂÙ·È Û ÂÚÈÙÒÛÂȘ ÌÂÁ·Ï‡ÙÂÚˆÓ ·È‰ÈÒÓ Ì Ôχ ¯·ÌËÏfi ·Ó¿ÛÙËÌ· (46). ¶Ú¤ÂÈ, fï˜, Ó· ÛËÌÂȈı› fiÙÈ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ıÂڷ›·˜ ÌÂ Û˘Ì‚·ÙÈΤ˜ ‰fiÛÂȘ rhGH ηÈ, Ôχ ÂÚÈÛÛfiÙÂÚÔ, Ì ˘„ËϤ˜ ‰fiÛÂȘ rhGH, Â›Ó·È ··Ú·›ÙËÙË Ë Ì¤ÙÚËÛË ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ IGF-I Î·È IGFBP-3 οı 6-12 Ì‹Ó˜, ÁÈ· Ó· ÚÔÛ‰ÈÔÚÈÛı› Ë ··ÈÙÔ‡ÌÂÓË ‰fiÛË rhGH Î·È Ó· ·ÔÊ¢¯ıÔ‡Ó Èı·Ó¤˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ (47). ∆· ·È‰È¿ Ì ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· GH ÏfiÁˆ Ï¢¯·ÈÌ›·˜ ‹ fiÁÎˆÓ ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ·ÔÙÂÏÔ‡Ó Ì›· ȉȷ›ÙÂÚË ÔÌ¿‰· ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ··ÓÙÔ‡Ó ÛÙÔÓ ›‰ÈÔ ‚·ıÌfi ÛÙË ıÂڷ›· Ì rhGH, ÏfiÁˆ Ù˘ ·ÎÙÈÓÔ‚ÔÏ›·˜ ÎÚ·Ó›Ô˘ ‹ Î·È ÛÔÓ‰˘ÏÈ΋˜ ÛÙ‹Ï˘ (™™). ŒÙÛÈ, Ù· ·È‰È¿ Ô˘ ¤Ï·‚·Ó ·ÎÙÈÓÔ‚ÔÏ›· ™™ ÌÂÙ¿ ·ÁˆÁ‹ Ì rhGH ÂÈÙ˘Á¯¿ÓÔ˘Ó
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¯·ÌËÏfiÙÂÚÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ·fi ÂΛӷ Ô˘ ‰ÂÓ ¤Ï·‚·Ó ·ÎÙÈÓÔ‚ÔÏ›· ™™ (11,48). To ÁÂÁÔÓfi˜ ·˘Ùfi ·Ô‰›‰ÂÙ·È ÛÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿Ù˘Í˘ Ù˘ ™™ ÌÂÙ¿ ÙËÓ ·ÎÙÈÓÔ‚ÔÏ›·, Ë ÔÔ›· Â›Ó·È ·Ó¿ÏÔÁË Ù˘ ‰fiÛ˘ Ù˘ (48). ŒÓ· ¿ÏÏÔ Úfi‚ÏËÌ· ÛÙ· ·È‰È¿ ·˘Ù¿ Â›Ó·È fiÙÈ Ë ·ÎÙÈÓÔ‚ÔÏ›· ÎÚ·Ó›Ô˘ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ‹‚˘. º˘ÛÈÔÏÔÁÈο, Ë ·Ó¿Ù˘ÍË Î·Ù¿ ÙËÓ ÚÔÂÊË‚È΋ ÂÚ›Ô‰Ô ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙËÓ ·‡ÍËÛË ÙˆÓ Ì·ÎÚÒÓ ÔÛÙÒÓ, ÂÓÒ Î·Ù¿ ÙËÓ ÂÊ˂›· Ì ÙËÓ ·‡ÍËÛË Ù˘ ™™. ™˘ÓÂÒ˜, Ë ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ‹‚˘ ÛÙ· ·È‰È¿ Ì ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· GH Ô‰ËÁ› ÛÙË ‚Ú¿¯˘ÓÛË Ù˘ ÚÔÂÊË‚È΋˜ ÂÚÈfi‰Ô˘ Î·È ÛÙË ÌË ÈηÓÔÔÈËÙÈ΋ ·‡ÍËÛË ÙˆÓ Ì·ÎÚÒÓ ÔÛÙÒÓ. ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ·Ó·Ê¤ÚÔ˘Ó fiÙÈ Ì ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ‹‚˘ ÛÙ· ·È‰È¿ ·˘Ù¿ Ì ¯ÔÚ‹ÁËÛË GnRHan, ·Ú¿ÏÏËÏ· Ì ÙË ¯ÔÚ‹ÁËÛË rhGH, ÂÈÙ˘Á¯¿ÓÂÙ·È Î·Ï‡ÙÂÚÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ·fi ÂΛÓÔ Ô˘ ÂÈÙ˘Á¯¿ÓÂÙ·È ÌfiÓÔ Ì ÙË ¯ÔÚ‹ÁËÛË rhGH (49). ∂›Û˘, ÛËÌ·ÓÙÈ΋ Â›Ó·È Ë ¤ÁηÈÚË ¤Ó·ÚÍË rhGH Û ·È‰È¿ Ì ÂÓ‰ÔÎÚ·ÓÈ·ÎÔ‡˜ fiÁÎÔ˘˜, Ì ‹ ¯ˆÚ›˜ ·ÎÙÈÓÔ‚ÔÏ›· ÎÚ·Ó›Ô˘, Ë ¯ÔÚ‹ÁËÛË ÙˆÓ Û˘Ó‹ıˆÓ (Î·È fi¯È ¯·ÌËÏÒÓ) ‰fiÛÂˆÓ rhGH, ηıÒ˜ ›Û˘ Î·È Ë ¯ÔÚ‹ÁËÛË Ù˘ ¯·ÌËÏfiÙÂÚ˘ ‰˘Ó·Ù‹˜ ‰fiÛ˘ ·ÎÙÈÓÔ‚ÔÏ›·˜ ™™ (48). ™˘ÌÂÚ·ÛÌ·ÙÈο, Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È ‰˘Ó·Ùfi Ó· ÂÈÙ¢¯ı› Ê˘ÛÈÔÏÔÁÈÎfi ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· Û ·È‰È¿ Ì IGHD Ì ÙË ¯ÔÚ‹ÁËÛË Û˘Ì‚·ÙÈÎÒÓ ‰fiÛÂˆÓ rhGH, ÂÊfiÛÔÓ Ë ¤Ó·ÚÍË Ù˘ ·ÁˆÁ‹˜ Á›ÓÂÈ Û ÌÈÎÚ‹ ËÏÈΛ· Î·È ÂÍ·ÛÊ·Ï›˙ÂÙ·È Û˘ÌÌfiÚʈÛË Ì ÙËÓ Î·ıËÌÂÚÈÓ‹ ¯ÔÚ‹ÁËÛË, ηıÒ˜ Î·È Ì·ÎÚ¿ ÚÔÂÊË‚È΋ ¯ÔÚ‹ÁËÛË Ù˘ rhGH (50), Ô‡Ùˆ˜ ÒÛÙ ӷ ÂÈÙ¢¯ı› ÈηÓÔÔÈËÙÈÎfi ‡„Ô˜ ÚÈÓ ÙËÓ ÂÊ˂›·. ŸÌˆ˜, Â¿Ó ˘¿Ú¯Ô˘Ó ηı˘ÛÙÂÚË̤ÓË ‰È¿ÁÓˆÛË, ÁÔÓ›˜ Ì ¯·ÌËÏfi ·Ó¿ÛÙËÌ· ‹ ÂÍ·ÈÚÂÙÈο ¯·ÌËÏfi ‡„Ô˜ ηٿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜, Û˘ÓÈÛÙ¿Ù·È ÌÈ· ÈÔ ÂÍ·ÙÔÌÈÎÂ˘Ì¤ÓË Î·È ÂÈıÂÙÈ΋ ıÂڷ›·. ∂›Û˘, Ú¤ÂÈ Ó· ˘ÔÁÚ·ÌÌÈÛı› Ë ÛËÌ·Û›· Ù˘ ¤ÁηÈÚ˘ ¤Ó·Ú͢ Ù˘ ·ÁˆÁ‹˜ Ì rhGH Û ·È‰È¿ Ì ÓÂÔÁÓÈ΋ ÌÂÌÔӈ̤ÓË GHD ‹ ÔÏÏ·Ï‹ ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ·, ηıÒ˜ Î·È Û ·È‰È¿ Ì ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· GH. ™ËÌ·ÓÙÈÎfi˜ Â›Ó·È Â›Û˘ Ô Â·Ó¤ÏÂÁ¯Ô˜ ÙˆÓ ·È‰ÈÒÓ Ì ·Ó¿ÚÎÂÈ· GH ÌÂÙ¿ ÙËÓ ÔÏÔÎÏ‹ÚˆÛË Ù˘ ıÂڷ›·˜, Ì ‰˘Ó·ÌÈΤ˜ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘ GH, ÁÈ· ÙÔ ÂӉ¯fiÌÂÓÔ Û˘Ó¤¯ÈÛ˘ Ù˘ ·ÁˆÁ‹˜ Ì rhGH ÛÙËÓ ÂÓ‹ÏÈÎÔ ˙ˆ‹.
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∫˘Úȷ΋ ∫·Ú·‚·Ó¿ÎË-∫·Ú·Ó¿ÛÈÔ˘
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the National Cooperative Growth Study Experience. Pediatrics 1999;86(10):4711-4716. 32. August GP, Julius JR, Blethen SL. Adult height in children with growth hormone deficiency who are treated with biosynthetic growth hormone: The National Cooperative Growth Study experience. Pediatrics 1998;102:512-516. 33. Cutfield W, Lindberg A, Albertsson-Wikland K, Chatelain P, Ranke MB, Wilton P, KIGS International Board. Final height in idiopathic growth hormone deficiency: the KIGS experience. Acta Paediatr Suppl 1999;428:72-75. 34. Ranke MB, Jonsson P. Who stops growth hormone therapy in KIGS -the International Kabi Growth Studyand why? KIGS Biannual Report 1995;12:33-40. 35. Smith SL, Hindmarsh PC, Brook CG. Compliance with growth hormone treatment - are they getting it? Arch Dis Child 1993;68:91-93. 36. Tauber M, Moulin P, Pienkowski C, Jouret B, Rochiccioli P. Growth hormone retesting and auxological data in 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab 1997;82:352-356. 37. Grumbach MM, Bin-Abbas BS, Kaplan SL. The growth hormone cascade: Progress and long-term results of growth hormone treatment in growth hormone deficiency. Horm Res 1998;49(suppl 2):41-57. 38. Gleeson H, Clayton PE. The transition from childhood to adulthood: Managing those with growth hormone deficiency. In: Ranke MB, Price DA, Reiter EO, editors. Growth Hormone Therapy in Pediatrics-20 years of KIGS. Basel: Karger; 2007. pp. 163-175. 39. ∫Ô‡ÛÙ· ∂, ¶··ı·Ó·Û›Ô˘ ∞, ÷Ù˙Ë·ı·Ó·Û›Ô˘ Ã. ∂Ӊ›ÍÂȘ ¯ÔÚ‹ÁËÛ˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ÛÙ· ·È‰È¿ Î·È ÙÔ˘˜ ÂÊ‹‚Ô˘˜. ¶·È‰È·ÙÚÈ΋ 2008;71:123-127. 40. Stefanidis CJ. Is rhGH anabolic in patients undergoing peritoneal dialysis? Br J Clin Pract Suppl 1996;85:44-46. 41. Rosen T, Johannsson G, Johansson JO, Bengtsson BA. Consequences of growth hormone deficiency in adults and the benefits and risks of recombinant human growth hormone treatment. A review paper. Horm Res 1995;43: 93-99. 42. Drake WM, Howell SJ, Monson JP, Shalet SM. Optimizing gh therapy in adults and children. Endocr Rev 2001;22: 425-450. 43. ¶··‰ÔÔ‡ÏÔ˘ ª, ¡ÙÔ˘Ì¿ ™, ∫›ÙÛÈÔ˜ ∫, ∫·‰fiÁÏÔ˘ ¡, ∫ÒÛÙ· ∫, ∆ÛÈÔ‡Ú˘ π. ∆ÂÏÈÎfi ·Ó¿ÛÙËÌ· Û ·È‰È¿ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Ô˘ ¤Ï·‚·Ó ıÂڷ›· ˘ÔηٿÛÙ·Û˘. ¶·È‰È·ÙÚÈ΋ 2008;71:128-134. 44. Rikken B, Massa GG, Wit JM. Final height in a large cohort of Dutch patients with growth hormone deficiency treated with growth hormone. Dutch Growth Hormone Working Group. Horm Res 1995;43:135-137. 45. Severi F. Final height in children with growth hormone deficiency. Horm Res 1995;43:138-140. 46. Ranke MB, Lindberg A, Martin DD. The mathematical model for total pubertal growth in idiopathic growth hormone (GH) deficiency suggests a moderate role of GH dose. J Clin Endocrinol Metab 2003;88:4748-4753. 47. Cohen P, Bright GM, Rogol AD, Kappelgaard AM, Rosenfeld RG. Effects of dose and gender on the growth and growth factor response to GH in GH-deficient children: implications for efficacy and safety. J Clin Endocrinol Metab 2002;87:90-98. 48. Brownstein CM, Mertens AC, Mitby PA, Stovall M, Qin J,
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Heller G, et al. Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: A report from the Childhood Cancer Survivor Study. J Clin Endocrinol & Metabolism 2004;89:4422-4427. 49. Gleeson HK, Stoeter R, Ogilvy-Stuart AL, Gattamaneni HR, Brennan BM, Shalet SM. Improvements in final
height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement. J Clin Endocrinol Metab 2003;88:3682-3689. 50. Reiter EO, Cutfield WS. Growth hormone deficiency: puberty and final height. In: Ranke MB, Price DA, Reiter EO, editors. Growth Hormone Therapy in Pediatrics. 20 years of KIGS. Basel: Karger; 2007. pp. 136-144.
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REVIEW ARTICLE
£Âڷ›· Ì ·˘ÍËÙÈ΋ ÔÚÌfiÓË ÛÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi ∂Ó‰ÔÎÚÈÓÔÏÔÁÈÎfi ∆Ì‹Ì· ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ «¶. & ∞. ∫˘ÚÈ·ÎÔ‡», ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ∂ϤÓË ∫Ô‡ÛÙ· lkousta@otenet.gr ™. ∞Ú‚·ÓÈÙ¿ÎË 6 ∫¤Ú΢ڷ 49100
E. ∫Ô‡ÛÙ·, Ã. ÷Ù˙Ë·ı·Ó·Û›Ô˘†, A. ¶··ı·Ó·Û›Ô˘ ¶ÂÚ›ÏË„Ë: ∆Ô Û‡Ó‰ÚÔÌÔ Prader-Willi Â›Ó·È ¤Ó· Û¿ÓÈÔ ÁÂÓÂÙÈÎfi Û‡Ó‰ÚÔÌÔ, ÙÔ ÔÔ›Ô ÔÊ›ÏÂÙ·È ÛÙËÓ ·ÒÏÂÈ· Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ Ù˘ ÂÚÈÔ¯‹˜ 15q11-q13 ÙÔ˘ ·ÙÚÈÎÔ‡ ·ÏÏËÏfiÌÔÚÊÔ˘ ·ÔÙ˘ˆÌ¤ÓÔ˘ ÁÔÓ›‰ÈÔ˘. ÷ڷÎÙËÚ›˙ÂÙ·È ·fi ÛÙ·‰È·Î¿ ·˘Í·ÓfiÌÂÓË ˘ÂÚÊ·Á›·, ·¯˘Û·ÚΛ·, ˘ÔÁÔÓ·‰ÈÛÌfi, ¯·ÌËÏfi ·Ó¿ÛÙËÌ· Î·È ¤ÏÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. ∆· ·È‰È¿ Î·È ÔÈ ÂÓ‹ÏÈΘ Ì ÙÔ Û‡Ó‰ÚÔÌÔ ·Ó·Ù‡ÛÛÔ˘Ó ÓÔÛÔÁfiÓÔ ·¯˘Û·ÚΛ·, Ë ÔÔ›· Â›Ó·È Ë Î‡ÚÈ· ·ÈÙ›· Ù˘ ·˘ÍË̤Ó˘ ıÓËÛÈÌfiÙËÙ·˜ Ô˘ ·Ú·ÙËÚ›ٷÈ. ∏ ηı˘ÛÙ¤ÚËÛË Ù˘ ·Ó¿Ù˘Í˘ ÍÂÎÈÓ¿ ÌÂÙ¿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ˙ˆ‹˜, ‰È·ÙËÚÂ›Ù·È ÛÙËÓ ·È‰È΋ ËÏÈΛ· Î·È Î·Ù·Ï‹ÁÂÈ Û˘Ó‹ıˆ˜ Û ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ¯·ÌËÏfiÙÂÚÔ ÙÔ˘ ‡„Ô˘˜-ÛÙfi¯Ô˘ Î·È Û˘Ó‹ıˆ˜ οو ·fi Ù· fiÚÈ· ÙÔ˘ Ê˘ÛÈÔÏÔÁÈÎÔ‡. ¶ÚfiÛÊ·Ù· ·Ú·ÙËÚ‹ıËΠıÂÙÈ΋ ›‰Ú·ÛË Ù˘ ıÂڷ›·˜ Ì ·˘ÍËÙÈ΋ ÔÚÌfiÓË, Ë ÔÔ›· ÂÈÙ·¯‡ÓÂÈ ÙÔÓ Ú˘ıÌfi ·‡ÍËÛ˘ Î·È ‚ÂÏÙÈÒÓÂÈ ÙÔ ¤ÏÏÂÈÌÌ· ‡„Ô˘˜ ÙˆÓ ·È‰ÈÒÓ. E›Ó·È Èı·ÓfiÓ Ë ıÂڷ›·, ¯ÔÚËÁÔ‡ÌÂÓË Ì·ÎÚÔ¯ÚfiÓÈ·, Ó· ‚ÂÏÙÈÒÓÂÈ ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ·. ∫˘Ú›ˆ˜, fï˜, ‚ÂÏÙÈÒÓÂÈ ÙË ÛˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË, ·˘Í¿ÓÔÓÙ·˜ ÙËÓ ¿ÏÈÔ Ì¿˙·, ÌÂÈÒÓÔÓÙ·˜ ÙÔÓ ÏÈÒ‰Ë ÈÛÙfi Î·È ‚ÂÏÙÈÒÓÔÓÙ·˜ ÙȘ ÂÓÂÚÁÂȷΤ˜ ‰·¿Ó˜, ¯ˆÚ›˜ ȉȷ›ÙÂÚ· ÛËÌ·ÓÙÈ΋ ÂÏ¿ÙÙˆÛË ÙÔ˘ BMI. ∂›Û˘, ‚ÂÏÙÈÒÓÂÈ ÙË Ì˘˚΋ ‰‡Ó·ÌË Î·È ÙËÓ ÎÈÓËÙÈÎfiÙËÙ· ÙˆÓ ÌÈÎÚÒÓ ·È‰ÈÒÓ. ∏ ÈÔ Û˘¯Ó‹ ·ÚÂÓ¤ÚÁÂÈ· Ù˘ ıÂڷ›·˜ Â›Ó·È Ë ÛÎÔÏ›ˆÛË. √È Ì·ÎÚÔÚfiıÂÛ̘ ÂÈÙÒÛÂȘ Ù˘ ıÂڷ›·˜ Ì ·˘ÍËÙÈ΋ ÔÚÌfiÓË ÛÙ· ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi, ȉȷ›ÙÂÚ· fiÛÔÓ ·ÊÔÚ¿ ÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÁÏ˘Îfi˙˘, Â›Ó·È ·ÎfiÌË ˘fi ‰ÈÂÚ‡ÓËÛË. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ Ì GH ·Ú·ÙËÚ‹ıËÎ·Ó ·ÈÊÓ›‰ÈÔÈ ı¿Ó·ÙÔÈ, ΢ڛˆ˜ ·fi ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ Î·È ˘Ô·ÂÚÈÛÌfi. √È ·Ú·ÙËÚ‹ÛÂȘ ·˘Ù¤˜ Ô‰‹ÁËÛ·Ó Û ÚÔ‚ÏËÌ·ÙÈÛÌfi ˆ˜ ÚÔ˜ ÙËÓ ·ÛÊ¿ÏÂÈ· Ù˘ ıÂڷ›·˜ Î·È ÙÔÓ›˙Ô˘Ó ÙË ÛËÌ·Û›· Ù˘ Ù·ÎÙÈ΋˜ Î·È ÚÔÛÂÎÙÈ΋˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ηٿ ÙË ıÂڷ›·. ∆Ô ‡„Ô˜ Û¿ÓÈ· ·ÔÙÂÏ› ÙÔ Î˘Ú›·Ú¯Ô Úfi‚ÏËÌ· ÙˆÓ ·È‰ÈÒÓ ·˘ÙÒÓ Î·È ÙˆÓ ÔÈÎÔÁÂÓÂÈÒÓ ÙÔ˘˜, ÏfiÁˆ ÙˆÓ ÔÏÏ·ÏÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ Ô˘ ·ÓÙÈÌÂÙˆ›˙Ô˘Ó. ∏ ıÂڷ›· Ì ·˘ÍËÙÈ΋ ÔÚÌfiÓË Ú¤ÂÈ Ó· ¯ÔÚËÁÂ›Ù·È ÛÙ· ·È‰È¿ ηÙfiÈÓ ÂÈÏÔÁ‹˜, ÁÈ· ‚ÂÏÙ›ˆÛË ÙfiÛÔ Ù˘ ·‡ÍËÛ˘ fiÛÔ Î·È Ù˘ Û‡ÛÙ·Û˘ ÛÒÌ·ÙÔ˜, Èı·ÓfiÓ ‰Â ÛÙÔ Ì¤ÏÏÔÓ Ó· ÁÂÓÈ΢ı›, ÂÊfiÛÔÓ ‚ÂÏÙÈÒÓÂÈ ÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi Î·È ÂÏ·ÙÙÒÓÂÈ ÙË ÌÂÏÏÔÓÙÈ΋ ÓÔÛËÚfiÙËÙ·. §¤ÍÂȘ ÎÏÂȉȿ: ™‡Ó‰ÚÔÌÔ Prader-Willi, ·˘ÍËÙÈ΋ ÔÚÌfiÓË, ·‡ÍËÛË, ۈ̷ÙÈ΋ Û‡ÛÙ·ÛË.
Growth hormone treatment in Prader-Willi syndrome Department of Endocrinology, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece Correspondence: Eleni Kousta lkousta@otenet.gr 6, Sp. Arvanitaki St. 49100, Kerkyra Greece
E. Kousta, C. Hadjiathanasiou†, A. Papathanasiou Abstract: Prader-Willi syndrome is a rare genetic disorder caused by the lack of expression of the paternally derived imprinted genes on the chromosome region 15q11-q13. It is characterized by gradual development of hyperphagia, obesity, hypogonadism, short stature and growth hormone (GH) deficiency. Children and adults with the syndrome develop morbid obesity, which is the main cause of the associated increased mortality. Growth retardation develops during the first year of life, and persists through childhood, leading to reduction in the final height. Recent observations suggest that GH replacement therapy improves the growth rate and height deficit in these children. Long term therapy is likely to improve final height. GH therapy also improves body composition by increasing fat free mass, decreasing fat mass and improving resting energy expenditure; however it does not seem to affect the body mass index (BMI) significantly. πn addition, it improves muscle strength and motility in younger children. The commonest side effect of the treatment is scoliosis. The long term consequences of GH treatment in children with Prader-Willi syndrome, particularly regarding carbohydrate metabolism, are still under investigation. Sudden death has been reported in children receiving GH, mainly related to hypoventilation and upper airway infection, raising concerns about the safety of GH treatment and indicating the need for regular and careful monitoring. Considering the multiple problems facing children with Prader-Willi syndrome and their families, short stature does not constitute the main health concern. Treatment with GH is currently recommended in selected children to improve growth and body composition. It is possible that further studies concerning the effects of GH on metabolism and morbidity may lead to generalization of its use.
Key words: Prader-Willi syndrome, growth hormone, growth, body composition.
∞ÊÈÂڈ̤ÓÔ ÛÙË ÌÓ‹ÌË ÙÔ˘ ÷ڿϷÌÔ˘ ÷Ù˙Ë·ı·Ó·Û›Ô˘
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∞˘ÍËÙÈ΋ ÔÚÌfiÓË ÛÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi
™˘ÓÙÔÌÔÁڷʛ˜ FHtSDS final height SDS - ÛÎÔÚ ÛÙ·ıÂÚ‹˜ ·fiÎÏÈÛ˘ ÙÂÏÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜ GH growth hormone - ·˘ÍËÙÈ΋ ÔÚÌfiÓË HtSDS height SDS - ÛÎÔÚ ÛÙ·ıÂÚ‹˜ ·fiÎÏÈÛ˘ ‡„Ô˘˜ IGF-1 insulin-like growth factor 1 - ÈÓÛÔ˘ÏÈÓfiÌÔÚÊÔ˜ ·˘ÍËÙÈÎfi˜ ·Ú¿ÁˆÓ 1 SDS standard deviation score - ÛÎÔÚ ÛÙ·ıÂÚ‹˜ ·fiÎÏÈÛ˘
EÈÛ·ÁˆÁ‹ ∆Ô Û‡Ó‰ÚÔÌÔ Prader-Willi Â›Ó·È ¤Ó· Û¿ÓÈÔ ÁÂÓÂÙÈÎfi Û‡Ó‰ÚÔÌÔ, Ë Û˘¯ÓfiÙËÙ· ÙÔ˘ ÔÔ›Ô˘ ˘ÔÏÔÁ›˙ÂÙ·È Û 1/10.000 - 1/15.000 ÁÂÓÓ‹ÛÂȘ (1). √Ê›ÏÂÙ·È ÛÙËÓ ·ÒÏÂÈ· Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ Ù˘ ÂÚÈÔ¯‹˜ 15q11-q13, Ë ÔÔ›· ÂÎÊÚ¿˙ÂÙ·È ÌfiÓÔ ·fi ÙÔ ·ÙÚÈÎfi ÁÔÓ›‰ÈÔ (·ÙÚÈÎfi ·ÏÏËÏfiÌÔÚÊÔ ·ÔÙ˘ˆÌ¤ÓÔ ÁÔÓ›‰ÈÔ). ∆· ·ÓÙ›ÛÙÔȯ· ÁÔÓ›‰È· ÌËÙÚÈ΋˜ ÚÔ¤Ï¢Û˘ Â›Ó·È Ê˘ÛÈÔÏÔÁÈο ·ÓÂÓÂÚÁ¿. ™ÙËÓ ÏÂÈÔ„ËÊ›· ÙˆÓ ÂÚÈÙÒÛÂˆÓ (70-75%), Ë ·ÒÏÂÈ· Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ ·˘Ù‹˜ Ù˘ ÂÚÈÔ¯‹˜ ÔÊ›ÏÂÙ·È Û ·¿ÏÂÈ„Ë ·˘Ù‹˜ Ù˘ ÁÔÓȉȷ΋˜ ÂÚÈÔ¯‹˜ ·fi ÙÔ ·ÙÚÈÎfi ¯ÚˆÌfiۈ̷ 15, Û 20-25% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Î·È ÔÈ ‰‡Ô ·˘Ù¤˜ ÁÔÓȉȷΤ˜ ÂÚÈÔ¯¤˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15 ·fi ÙË ÌËÙ¤Ú· (ÌËÙÚÈ΋ ‰Èۈ̛·), Û 2-5% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ˘¿Ú¯ÂÈ ÌÈÎÚÔ·¿ÏÂÈ„Ë ÂÓfi˜ ÁÂÓÂÙÈÎÔ‡ ÛÙÔÈ¯Â›Ô˘ Ô˘ ÔÓÔÌ¿˙ÂÙ·È Î¤ÓÙÚÔ ·ÔÙ‡ˆÛ˘ (imprinting center) (Û¿ÓÈ· ˘¿Ú¯ÂÈ ‰È·Ù·Ú·¯‹ ÛÙË ÁÔÓȉȷ΋ ·ÔÙ‡ˆÛË ·˘Ù‹˜ Ù˘ ÂÚÈÔ¯‹˜ ¯ˆÚ›˜ Ó· ˘¿Ú¯Ô˘Ó ÁÔÓȉȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ) Î·È Û 1% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ˘¿Ú¯Ô˘Ó ÌÂÙ·ı¤ÛÂȘ Û’ ·˘Ù‹ ÙË ÁÔÓȉȷ΋ ÂÚÈÔ¯‹ (1,2). ™ÙË ÁÔÓȉȷ΋ ÂÚÈÔ¯‹ 15q11-q13 ¤¯Ô˘Ó ÂÓÙÔÈÛÙ› ·ÚÎÂÙÔ› ·ÙÚÈο ÂÎÊÚ·˙fiÌÂÓÔÈ ÁÔÓȉȷÎÔ› ÙfiÔÈ (MKRN3, MAGEL2, NDN Î·È SNURFSNRPN). ™ÙËÓ ·Ú·Î›ÌÂÓË ÛÙÔ ÁÔÓ›‰ÈÔ SNURFSNRPN ÂÚÈÔ¯‹ ÂÓÙÔ›˙ÔÓÙ·È ÔÏÏ·Ï¿ ÂÛÒÓÈ·, Ù· ÔÔ›· ÂÚȤ¯Ô˘Ó ÁÔÓ›‰È· ÁÈ· ÌË Îˆ‰ÈÎÔÔÈÔ‡ÓÙ· RNA (C/D box snoRNA - ÌÈÎÚfi RNA ˘ÚËÓ›ÛÎÔ˘ Ù‡Ô˘ C/D box). Œˆ˜ ÙÒÚ·, ‰ÂÓ Â›¯Â ·Ô‰Âȯı› ÔÈÔ ‹ ÔÈ· ·fi Ù· ·ÙÚÈο ÂÎÊÚ·˙fiÌÂÓ· ÁÔÓ›‰È· ·˘Ù‹˜ Ù˘ ÂÚÈÔ¯‹˜ Û˘Ó‰¤ÔÓÙ·È Ì ÙË ÓfiÛÔ Î·È Ì ÔÈÔ Ì˯·ÓÈÛÌfi. ™Â ÚfiÛÊ·ÙË ÌÂϤÙË ÂÓÙÔ›ÛÙËΠÌÈÎÚÔ·¿ÏÂÈ„Ë Ù˘ ÁÔÓȉȷ΋˜ ÂÚÈÔ¯‹˜ ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ HBII-85snoRNA Û ¤Ó· ·ÁfiÚÈ Ì ÙÔ Û‡Ó‰ÚÔÌÔ Î·È Â›Ó·È Èı·ÓfiÓ Ë ·¿ÏÂÈ„Ë Ù˘ ÂÚÈÔ¯‹˜ ·˘Ù‹˜ Ó· Û˘Ì‚¿ÏÏÂÈ ÛËÌ·ÓÙÈο ÛÙÔÓ Ê·ÈÓfiÙ˘Ô ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ (3). ∆· Û˘ÁÎÂÎÚÈ̤ӷ ÁÔÓ›‰È· ÙˆÓ snoRNAs ÂÎÊÚ¿˙ÔÓÙ·È Î˘Ú›ˆ˜ ÛÙÔÓ ÂÁΤʷÏÔ, fï˜ Ô ·ÎÚÈ‚‹˜ Ì˯·ÓÈÛÌfi˜ ‰Ú¿Û˘ ÙÔ˘˜ ‰ÂÓ Â›Ó·È ·ÎfiÌË ÁÓˆÛÙfi˜. √È ÏËÚÔÊÔڛ˜ ·˘Ù¤˜ Èı·ÓfiÓ Ó· Ô‰ËÁ‹ÛÔ˘Ó Û ηχÙÂÚË Î·Ù·ÓfiËÛË Ù˘ ·ıÔÁ¤ÓÂÈ·˜ Ù˘ ÓfiÛÔ˘ Î·È ›Ûˆ˜ Û Ӥ˜ ıÂڷ¢ÙÈΤ˜ ‰˘Ó·ÙfiÙËÙ˜. ∆Ô Û‡Ó‰ÚÔÌÔ Prader-Willi Â›Ó·È ÌÈ· ÔÏ˘Û˘ÛÙË-
Ì·ÙÈ΋ ÓfiÛÔ˜ Ë ÔÔ›· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ˘ÂÚÊ·Á›·, ·¯˘Û·ÚΛ·, ˘ÔÁÔÓ·‰ÈÛÌfi, ¯·ÌËÏfi ·Ó¿ÛÙËÌ· Î·È ¤ÏÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GH) ÔÊÂÈÏfiÌÂÓË Û ˘Ôı·Ï·ÌÈ΋ ‰È·Ù·Ú·¯‹ (2,5). O ‚·ıÌfi˜ Ù˘ ¤ÏÏÂȄ˘ GH ÔÈΛÏÏÂÈ ·fi ̤ÙÚÈ· ¤ˆ˜ Ï‹ÚË ·Ó¿ÚÎÂÈ· Î·È Û˘Ó‹ıˆ˜ Ù· ›‰· IGF-1 (ÈÓÛÔ˘ÏÈÓfiÌÔÚÊÔ˜ ·˘ÍËÙÈÎfi˜ ·Ú¿ÁˆÓ 1) Â›Ó·È ¯·ÌËÏ¿, ·Ú¿ ÙËÓ ·¯˘Û·ÚΛ·. ¶ÔÏÏ¿ ·fi Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ÁÓˆÚ›ÛÌ·Ù· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘, fiˆ˜ Ë ˘ÂÚÊ·Á›·, Ë ˘ÓËÏ›·, Ô ·˘ÙÔÙÚ·˘Ì·ÙÈÛÌfi˜ ÙÔ˘ ‰¤ÚÌ·ÙÔ˜ Î·È Ô ˘ÔÁÔÓ·‰ÈÛÌfi˜, ÌÔÚÔ‡Ó Ó· ·Ô‰ÔıÔ‡Ó Û ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ˘Ôı·Ï¿ÌÔ˘. ∏ ÛÔ‚·ÚÔ‡ ‚·ıÌÔ‡ ˘ÔÙÔÓ›· Î·È ·‰˘Ó·Ì›· ÚÔηÏÔ‡Ó Ì›ˆÛË ÙˆÓ ÎÈÓ‹ÛÂˆÓ ÙÔ˘ ÂÌ‚Ú‡Ô˘, ‰˘ÛÎÔϛ˜ Û›ÙÈÛ˘ ÌÂÙ¿ ÙË Á¤ÓÓËÛË, ·‰‡Ó·ÌÔ ÎÏ¿Ì· ‹ ·Ô˘Û›· ÎÏ¿Ì·ÙÔ˜ Î·È ÓˆıÚfiÙËÙ· ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ‚ÚÂÊÈ΋˜ ËÏÈΛ·˜, Ì ηı˘ÛÙ¤ÚËÛË ·Ó¿Ù˘Í˘ Î·È ·Ó·Ú΋ ÚfiÛÏË„Ë ‚¿ÚÔ˘˜ (4,6). √ Ì˘˚Îfi˜ ÙfiÓÔ˜ Î·È ÔÈ ÎÈÓ‹ÛÂȘ ‚ÂÏÙÈÒÓÔÓÙ·È ÚÔ˜ ÙÔ Ù¤ÏÔ˜ ÙÔ˘ ÚÒÙÔ˘ ¯ÚfiÓÔ˘ Ù˘ ˙ˆ‹˜ ηÈ, ·Ó Î·È Î·ı˘ÛÙÂÚË̤ӷ, ÂÈÙ˘Á¯¿ÓÔÓÙ·È Ù· ·Ó·Ù˘Íȷο ÔÚfiÛËÌ·. ∫·Ù¿ ÙÔ 2Ô ‹ 3Ô ¤ÙÔ˜ Ù˘ ˙ˆ‹˜ ÍÂÎÈÓ¿ Ë Ê¿ÛË Ù˘ ˘ÂÚÊ·Á›·˜, Ë ÔÔ›·, ·Ó ‰ÂÓ ÂÏÂÁ¯ı›, ÂÍÂÏ›ÛÛÂÙ·È Û ÛÔ‚·ÚÔ‡ ‚·ıÌÔ‡ ·¯˘Û·ÚΛ·. ∆· ·È‰È¿ ÂÌÊ·Ó›˙Ô˘Ó ¯·Ú·ÎÙËÚÈÛÙÈ΋ ÂÌÌÔÓ‹ Î·È ÎÚ›ÛÂȘ ı˘ÌÔ‡, ÛÙËÓ ÚÔÛ¿ıÂÈ· ÙˆÓ ÁÔÓ¤ˆÓ Ó· ÂϤÁÍÔ˘Ó Î·È Ó· ÂÚÈÔÚ›ÛÔ˘Ó ÙÔ Ê·ÁËÙfi (4,6). √ ˘ÔÁÔÓ·‰ÈÛÌfi˜ ÂΉËÏÒÓÂÙ·È Ì ηı˘ÛÙ¤ÚËÛË ÙˆÓ ÛËÌ›ˆÓ Ù˘ ‹‚˘ ÛÙ· ÎÔÚ›ÙÛÈ·, Û·ÓÈfiÙÂÚ· ‰Â ÌÔÚ› Ó· ˘¿Ú¯ÂÈ ·Ú·ÈÔÌËÓfiÚÚÔÈ· ‹ ·ÌËÓfiÚÚÔÈ·. ∆· ·ÁfiÚÈ· ·ÚÔ˘ÛÈ¿˙Ô˘Ó Û˘Ó‹ıˆ˜ ÎÚ˘„ÔÚ¯›· ηٿ ÙË Á¤ÓÓËÛË Î·È, ·Ú¿ ÙËÓ ÂÈÙ˘¯‹ ÔÚ¯ÂÔËÍ›·, ¯ÚÂÈ¿˙ÔÓÙ·È ıÂڷ›· Ì ·Ó‰ÚÔÁfiÓ· ÁÈ· ÙËÓ ¤Ó·ÚÍË Î·È ÚfiÔ‰Ô Ù˘ ‹‚˘. √È ÂÓ‹ÏÈΘ Ì ÙÔ Û‡Ó‰ÚÔÌÔ ·Ó·Ù‡ÛÛÔ˘Ó Û˘Ó‹ıˆ˜ ÓÔÛÔÁfiÓÔ ·¯˘Û·ÚΛ·, Ë ÔÔ›· Â›Ó·È Ë Î‡ÚÈ· ·ÈÙ›· Ù˘ ·˘ÍË̤Ó˘ ıÓËÛÈÌfiÙËÙ·˜. ∏ ·¯˘Û·ÚΛ· Ô‰ËÁ› Û ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ II, ηډȷÁÁÂȷ΋ ÓfiÛÔ, ˘¤ÚÙ·ÛË, ˘ÂÚÏÈȉ·ÈÌ›·, ıÚÔÌ‚ÔÊÏ‚›Ùȉ·, ¯ÚfiÓÈÔ Ô›‰ËÌ· οو ¿ÎÚˆÓ, ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ‡ÓÔ˘, ‰È·Ù·Ú·¯¤˜ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È „˘¯ÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜, fiˆ˜ ηٿıÏÈ„Ë Î·È ÂÏ·Ùو̤ÓË ·˘ÙÔÂÎÙ›ÌËÛË (5). ¶ÂÚ›Ô˘ 80% ÙˆÓ ·ÛıÂÓÒÓ ¤¯Ô˘Ó ÛÎÔÏ›ˆÛË. ∂›Û˘, ÂÌÊ·Ó›˙Ô˘Ó Û˘¯Ó¿ ÔÛÙÂÔfiÚˆÛË, Èı·ÓfiÓ ÏfiÁˆ ÙÔ˘ ˘ÔÁÔÓ·‰ÈÛÌÔ‡ Î·È Ù˘ ¤ÏÏÂȄ˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘.
∏ ·‡ÍËÛË ÛÙ· ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi ∂ÓÒ ÙÔ ‡„Ô˜ ηٿ ÙË Á¤ÓÓËÛË Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎfi ‹ ˘ÔÏ›ÂÙ·È ÂÏ¿¯ÈÛÙ·, Ô Ú˘ıÌfi˜ ·‡ÍËÛ˘ ηı˘ÛÙÂÚ› ηٿ ÙË ‚ÚÂÊÈ΋ ËÏÈΛ·, Èı·ÓfiÓ ÏfiÁˆ ÌÂȈ̤Ó˘ ÚfiÛÏ˄˘ ıÂÚÌ›‰ˆÓ. ∆Ô ·Ó¿ÛÙËÌ· ·Ú·Ì¤ÓÂÈ ¯·ÌËÏfi [ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË ‡„Ô˘˜ (∏tSDS) ~ -2] ¶·È‰È·ÙÚÈ΋ 2009;72:10-15
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·12
12
E. ∫Ô‡ÛÙ· Î·È Û˘Ó.
ηı’ fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ·È‰È΋˜ ËÏÈΛ·˜, ·Ú¿ ÙÔÓ Û¯ÂÙÈο Ê˘ÛÈÔÏÔÁÈÎfi Ú˘ıÌfi ·‡ÍËÛ˘ (7,8). ™ËÌÂȈ٤ÔÓ fiÙÈ ‰ÂÓ ·Ú·ÙËÚÂ›Ù·È ÂÈÙ¿¯˘ÓÛË ÙÔ˘ Ú˘ıÌÔ‡ ·‡ÍËÛ˘, ·Ú¿ ÙËÓ ˘„ËÏ‹ ÂÓÂÚÁÂȷ΋ ÚfiÛÏË„Ë, Û ·ÓÙ›ıÂÛË Ì fi,ÙÈ Û˘Ì‚·›ÓÂÈ ÛÙËÓ ·Ï‹ ·¯˘Û·ÚΛ·. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÊ˂›·˜, Ô Ú˘ıÌfi˜ ·‡ÍËÛ˘ ÂÏ·ÙÙÒÓÂÙ·È, ÏfiÁˆ ·Ô˘Û›·˜ ÙÔ˘ ÂÊË‚ÈÎÔ‡ ¿ÏÌ·ÙÔ˜ ‡„Ô˘˜ (7,8,9). °È’ ·˘Ùfi, ÛÙ· ¿ÙÔÌ· Ì ۇӉÚÔÌÔ Prader-Willi Ë ÂηÙÔÛÙÈ·›· ı¤ÛË ÙÔ˘ ‡„Ô˘˜ ηٿ ÙËÓ ÂÓ‹ÏÈÎÔ ˙ˆ‹ Â›Ó·È ¯·ÌËÏfiÙÂÚË ·fi ÙËÓ ÂηÙÔÛÙÈ·›· ı¤ÛË ÙÔ˘ ‡„Ô˘˜ ηٿ ÙËÓ ·È‰È΋ ËÏÈΛ·. ∆Ô Ì¤ÛÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ÙˆÓ ·È‰ÈÒÓ ·˘ÙÒÓ Ô˘ ηٷÁÚ¿ÊËΠÛÙÔ ∏ӈ̤ÓÔ µ·Û›ÏÂÈÔ Â›Ó·È 147 cm (-2,8 SD) ÁÈ· Ù· ÎÔÚ›ÙÛÈ· Î·È 155 cm (-3,2 SD) ÁÈ· Ù· ·ÁfiÚÈ· (7).
™ˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË ™ÙËÓ ·Ï‹ ·¯˘Û·ÚΛ·, Ë ÏÈ҉˘ Ì¿˙· Â›Ó·È ·˘ÍË̤ÓË, ÂÓÒ Ë ¿ÏÈÔ˜ Ì¿˙· Ê˘ÛÈÔÏÔÁÈ΋ ‹ ·˘ÍË̤ÓË. ™ÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi ·Ú·ÙËÚÂ›Ù·È ÂÏ·Ùو̤ÓË ¿ÏÈÔ˜ Î·È ·˘ÍË̤ÓË ÏÈ҉˘ Ì¿˙·, ·ÎfiÌ· Î·È ÛÙ· ÏÂÙ¿ ¿ÙÔÌ· (10,11). ∂ÈϤÔÓ, Ë ÔÛÙÈ΋ ˘ÎÓfiÙËÙ· Â›Ó·È ÂÏ·Ùو̤ÓË Û ۇÁÎÚÈÛË Ì ÙËÓ ÎÔÈÓ‹ ·¯˘Û·ÚΛ· (10). ∞ÎfiÌ· Î·È ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ·, ηٿ ÙËÓ ÔÔ›· Ë ÛˆÌ·ÙÈ΋ Ì¿˙· ÛÙ· ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi Â›Ó·È ÂÏ·Ùو̤ÓË, Û ۯ¤ÛË Ì ٷ Ê˘ÛÈÔÏÔÁÈο ·È‰È¿, Ë ·Ó·ÏÔÁ›· ÙÔ˘ Ï›Ô˘˜ Â›Ó·È Û¯ÂÙÈο ·˘ÍË̤ÓË (12). ∏ ÂÏ·Ùو̤ÓË ¿ÏÈÔ˜ Ì¿˙· ÌÔÚ› Ó· ·ÓÙ·Ó·ÎÏ¿ ÂÏ·Ùو̤ÓË Ì˘˚΋ Ì¿˙·, Î·È ¤ÙÛÈ Ó· ÂÍËÁÂ›Ù·È ÂÓ Ì¤ÚÂÈ Î·È Ë ˘ÔÙÔÓ›· (5). √È ÂÓÂÚÁÂȷΤ˜ ‰·¿Ó˜ Â›Ó·È ÌÂȈ̤Ó˜, Èı·ÓfiÓ ÏfiÁˆ Ù˘ ÌÂȈ̤Ó˘ ·Ï›Ô˘ Ì¿˙·˜. °È· ÙÔ ÏfiÁÔ ·˘Ùfi, ÛÙ· ¿ÙÔÌ· Ì ۇӉÚÔÌÔ Prader-Willi ÔÈ ÂÓÂÚÁÂȷΤ˜ ·Ó¿ÁΘ ·Ó¿ ÌÔÓ¿‰· ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ Â›Ó·È ¯·ÌËÏfiÙÂÚ˜, Û ۯ¤ÛË Ì ٷ Ê˘ÛÈÔÏÔÁÈο ¿ÙÔÌ·, ÁÂÁÔÓfi˜ ÙÔ ÔÔ›Ô Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÙ·È ˘fi„Ë fiÙ·Ó ˘ÔÏÔÁ›˙ÂÙ·È Ë È‰·ÓÈ΋ ËÌÂÚ‹ÛÈ· ÚfiÛÏË„Ë ÙÚÔÊ‹˜ (13). £Âڷ›· Ì ·˘ÍËÙÈ΋ ÔÚÌfiÓË (GH) ∏ ›‰Ú·ÛË Ù˘ ıÂڷ›·˜ Ì GH ÛÙËÓ ·‡ÍËÛË ∏ ·Ó·Ú΋˜ ¤ÎÎÚÈÛË GH Î·È Ù· ¯·ÌËÏ¿ ›‰· IGF-1 ÛÙ· ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ·, Ô‰‹ÁËÛ·Ó ÛÙË ıÂڷ›· ÙˆÓ ·È‰ÈÒÓ Ì GH. ª¤¯ÚÈ Û‹ÌÂÚ·, ÂÚÈÛÛfiÙÂÚ· ·fi 300 ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi ·ÁÎÔÛÌ›ˆ˜ ¤¯Ô˘Ó ¿ÚÂÈ ıÂڷ›· Ì GH ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ·fi 6 Ì‹Ó˜ ¤ˆ˜ >5 ¯ÚfiÓÈ· (5,14). √È ·Ú¯ÈΤ˜ ÌÂϤÙ˜ ıÂڷ›·˜ ¤‰ÂÈÍ·Ó ÛËÌ·ÓÙÈ΋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· Ì GH ηٿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ıÂڷ›·˜ Î·È ‚ÂÏÙ›ˆÛË Ù˘ Ù·¯‡ÙËÙ·˜ ·‡ÍËÛ˘ (15,16,17), ¯ˆÚ›˜ ÂÈÙ¿¯˘ÓÛË Ù˘ ÔÛÙÈ΋˜ ËÏÈΛ·˜ (16). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ‰Â‡ÙÂÚÔ˘ ¤ÙÔ˘˜ ıÂڷ›·˜ Û 35 ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi, ̤Û˘ ËÏÈPaediatriki 2009;72:10-15
Λ·˜ 9,9 ÂÙÒÓ (‡ÚÔ˜ 4-16 ¤ÙË), ·Ú·ÙËÚ‹ıËΠÌÈÎÚ‹ ÙÒÛË ÙÔ˘ Ú˘ıÌÔ‡ ·‡ÍËÛ˘ (6,8 cm/¤ÙÔ˜) Û ۇÁÎÚÈÛË Ì ÙÔÓ ÚÔËÁÔ‡ÌÂÓÔ ¯ÚfiÓÔ (10,1 cm/¤ÙÔ˜), Ô Ú˘ıÌfi˜ fï˜ ·Ú¤ÌÂÈÓ ˘„ËÏfiÙÂÚÔ˜ Û ۯ¤ÛË Ì ÙÔÓ Ú˘ıÌfi ÚÈÓ ÙËÓ ¤Ó·ÚÍË ıÂڷ›·˜ (4,7 cm/¤ÙÔ˜) (18). ∏ ‰fiÛË Ù˘ GH ‹Ù·Ó 1 mg/m2/24ˆÚÔ (21 IU/m2/‚‰.) Î·È Ë Û˘ÓÔÏÈ΋ ·‡ÍËÛË Ù˘ HtSDS ‹Ù·Ó +0,8 ÌÂÙ¿ ·fi 2 ¯ÚfiÓÈ· ıÂڷ›·˜ (18). ¶·ÚfiÌÔÈ· Â˘Ú‹Ì·Ù· ·Ó·Ê¤ÚÔÓÙ·È Î·È Û ÂfiÌÂÓË ‰ÈÏ‹ Ù˘ÊÏ‹ ÌÂϤÙË 14 ·ÛıÂÓÒÓ Ô˘ ‹Ú·Ó ıÂڷ›· Ì GH (Û ‰fiÛË 0,3-0,6 IU/kg/‚‰.) ÁÈ· 3,6 ¯ÚfiÓÈ· (‡ÚÔ˜ 1-9,3 ¤ÙË) Î·È Û˘ÁÎÚ›ıËÎ·Ó Ì 14 ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Â›¯·Ó Ï¿‚ÂÈ ıÂڷ›· (19). ™ÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó ıÂڷ›·, Ô Ú˘ıÌfi˜ ·‡ÍËÛ˘ ·ÚÔ˘Û›·Û ÙË Ì¤ÁÈÛÙË ·‡ÍËÛË ÛÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÚÒÙÔ˘ ¤ÙÔ˘˜ Î·È ·Ú¤ÌÂÈÓ ˘„ËÏfiÙÂÚÔ˜ ηı’ fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ¯ÔÚ‹ÁËÛ˘, Û˘ÁÎÚÈÙÈο Ì ÙÔÓ ÚÔ Ù˘ ıÂڷ›·˜ Ú˘ıÌfi (19). ™Â ¿ÏÏË ÌÂϤÙË 18 ÚÔÂÊË‚ÈÎÒÓ ·ÛıÂÓÒÓ ËÏÈΛ·˜ 0,3-9,5 ÂÙÒÓ Ô˘ ¤Ï·‚·Ó ıÂڷ›· GH (Û ‰fiÛË 18 IU/m2/‚‰. ÁÈ· ·È‰È¿ <2 ÂÙÒÓ Î·È 24 IU/m2/ ‚‰. ÁÈ· ·È‰È¿ >2 ÂÙÒÓ) ÁÈ· ‰È¿ÛÙËÌ· 4 ÂÚ›Ô˘ ÂÙÒÓ, ·Ó·Ê¤ÚÂÙ·È Ì¤ÛË ·‡ÍËÛË Ù˘ HtSDS ηٿ 1,8 (20). ªÂÙ¿ ·fi Ù· ÚÒÙ· ¯ÚfiÓÈ· ıÂڷ›·˜, fiˆ˜ Î·È ÛÙȘ ÚÔËÁÔ‡ÌÂÓ˜ ÌÂϤÙ˜ ·Ú·ÙËÚ‹ıËΠۯÂÙÈ΋ ÂÈ‚Ú¿‰˘ÓÛË ÙÔ˘ Ú˘ıÌÔ‡ ·‡ÍËÛ˘. ∏ ÔÛÙÈ΋ ËÏÈΛ· ‰ÂÓ ÂÈÙ·¯‡ÓÂÙ·È Î·Ù¿ ÙË ıÂڷ›· Ì GH (21). ªÂÙ¿ ·fi ¤ÓÙ ¯ÚfiÓÈ· ıÂڷ›·˜ Ì GH (0,1 ‹ 0,2 IU/kg/24ˆÚÔ) Û ·È‰È¿ 3-12 ÂÙÒÓ, Ë HtSDS ·Ú¤ÌÂÈÓ ¿Óˆ ·fi ÙÔ Ì¤ÛÔ fiÚÔ ÁÈ· ÙË ¯ÚÔÓÔÏÔÁÈ΋ ËÏÈΛ· (22). ™ÙËÓ ›‰È· ÌÂϤÙË ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ë HtSDS ·˘Í‹ıËΠÛËÌ·ÓÙÈο ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÚÒÙÔ˘ ¯ÚfiÓÔ˘ Ù˘ ıÂڷ›·˜ Î·È Ë ÂηÙÔÛÙÈ·›· ı¤ÛË Ô˘ ›¯Â ÂÈÙ¢¯ı› ‰È·ÙËÚ‹ıËΠηٿ Ù· ÂfiÌÂÓ· ¯ÚfiÓÈ· Ù˘ ıÂڷ›·˜. H ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· Â›Ó·È ÁÂÓÈο ηχÙÂÚË ÛÙ· ·È‰È¿ ÚÔÂÊË‚È΋˜ ËÏÈΛ·˜, ·Ú¿ ÛÙÔ˘˜ ÂÊ‹‚Ô˘˜, fiˆ˜ Û˘Ì‚·›ÓÂÈ Î·È Ì ÙËÓ ÎÏ·ÛÈ΋ ¤ÏÏÂÈ„Ë (14). ŸÛÔÓ ·ÊÔÚ¿ ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· ÙˆÓ ·È‰ÈÒÓ Ì ۇӉÚÔÌÔ Prader-Willi Ô˘ ‹Ú·Ó ıÂڷ›· Ì GH, ·Ú¯Èο ·Ó·Ê¤ÚıËÎ·Ó ·ÔÙÂϤÛÌ·Ù· ÙÂÏÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜ ÁÈ· 4 ÌfiÓÔ ·È‰È¿, Ô˘ ‹Ú·Ó ıÂڷ›· ÁÈ· 5 ¯ÚfiÓÈ·. ∏ SDS ÙÔ˘ ÙÂÏÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜ (FHtSDS) Î˘Ì¿ÓıËΠ۠fiÚÈ· ±2SD, Û˘ÁÎÚÈÙÈο Ì ÙÔ ‡„Ô˜-ÛÙfi¯Ô (‡ÚÔ˜ -1,1 ¤ˆ˜ +0,9 SDS) (22). ¶ÚfiÛÊ·Ù· ·Ó·Ê¤ÚıËÎ·Ó Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ıÂڷ›·˜ Ì GH (Û ‰fiÛË 0,25±0,06 mg/kg/‚‰ÔÌ¿‰·) ÁÈ· 21 ·È‰È¿ ËÏÈΛ·˜ 8,3±2,7 ÂÙÒÓ Ì ۇӉÚÔÌÔ PraderWilli Î·È ∏tSDS -1,9±1,7, Ù· ÔÔ›· ‹Ú·Ó ıÂڷ›· ÁÈ· 7,9±1,7 ¯ÚfiÓÈ·, Û ۇÁÎÚÈÛË Ì 39 ÂÓ‹ÏÈΘ ·ÛıÂÓ›˜ Ì ÙÔ Û‡Ó‰ÚÔÌÔ ÔÈ ÔÔ›ÔÈ ‰ÂÓ ‹Ú·Ó ıÂڷ›· Ì GH Î·È ÔÈ ÔÔ›ÔÈ Â›¯·Ó ·Ó¿ÏÔÁË ∏tSDS ÛÙËÓ ËÏÈΛ· ÙˆÓ 6,8±1,3 ÂÙÒÓ (23). ∏ FHtSDS ‹Ù·Ó ÛËÌ·ÓÙÈο
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·13
13
∞˘ÍËÙÈ΋ ÔÚÌfiÓË ÛÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi
‚ÂÏÙȈ̤ÓË (-0,3±1,2) ÛÙ· ·È‰È¿ Ô˘ ‹Ú·Ó ÙË ıÂڷ›·, Û ۇÁÎÚÈÛË Ì ÙËÓ SDS ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ‹Ú·Ó ıÂڷ›· (-3,1±1,0) (23). ™˘ÓÂÒ˜, Ë ¯ÔÚ‹ÁËÛË GH ÁÈ· 1-3 ¯ÚfiÓÈ· ‚ÂÏÙÈÒÓÂÈ ÙÔ ‡„Ô˜ Î·È ÙÔÓ Ú˘ıÌfi ·‡ÍËÛ˘, ¯ˆÚ›˜ ȉȷ›ÙÂÚË ÂÈÙ¿¯˘ÓÛË Ù˘ ÔÛÙÈ΋˜ ËÏÈΛ·˜, ÛÙ· ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi. ¶·ÚfiÏÔ Ô˘ Ô ·ÚÈıÌfi˜ ÙˆÓ ·È‰ÈÒÓ Ì ıÂڷ›· Ô˘ ¤Êı·Û·Ó ÙÂÏÈÎfi ·Ó¿ÛÙËÌ· Â›Ó·È ÂÚÈÔÚÈṲ̂ÓÔ˜, Ì ٷ ˘¿Ú¯ÔÓÙ· ‰Â‰Ô̤ӷ Ê·›ÓÂÙ·È fiÙÈ Ë Â˘ÂÚÁÂÙÈ΋ ›‰Ú·ÛË Ù˘ ıÂڷ›·˜ ‰È·ÙËÚÂ›Ù·È Ì¤¯ÚÈ ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ·. ∏ ›‰Ú·ÛË Ù˘ ıÂڷ›·˜ Ì GH ÛÙË ÛˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË ·ÙfiÌˆÓ Ì ۇӉÚÔÌÔ Prader-Willi √È ÂÚÈÛÛfiÙÂÚ˜ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ Ë Â›‰Ú·ÛË Ù˘ GH ÛÙË ÛˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË Â›Ó·È Â˘ÂÚÁÂÙÈ΋: ·˘Í¿ÓÂÙ·È Ë ¿ÏÈÔ˜ Ì¿˙· Î·È ÌÂÈÒÓÂÙ·È Ô ÏÈ҉˘ ÈÛÙfi˜ (5,14). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÚÒÙÔ˘ ¯ÚfiÓÔ˘ ıÂڷ›·˜, ·Ó·Ê¤ÚıËΠÛËÌ·ÓÙÈ΋ ÂÏ¿ÙÙˆÛË Ù˘ ÛÙ·ıÂÚ‹˜ ·fiÎÏÈÛ˘ ÙÔ˘ ‰Â›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜ (µªπ SDS), ·‡ÍËÛË Î·Ù¿ ÙÔ˘˜ ÂfiÌÂÓÔ˘˜ 6 Ì‹Ó˜ ¯ˆÚ›˜ ıÂڷ›· Ì GH Î·È ÛÙ·ıÂÚÔÔ›ËÛË ÌÂÙ¿ ÙËÓ Â·Ó¤Ó·ÚÍË Ù˘ ¯ÔÚ‹ÁËÛ˘ (22). ™Â 35 ·ÛıÂÓ›˜ Ì ۇӉÚÔÌÔ Prader-Willi, ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ Ï›Ô˘˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÚÒÙÔ˘ ¯ÚfiÓÔ˘ Ù˘ ıÂڷ›·˜, ¯ˆÚ›˜ fï˜ Ó· ·Ú·ÙËÚËı› ÂÚ·ÈÙ¤Úˆ Ì›ˆÛË ÛÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ‰Â‡ÙÂÚÔ˘ ¯ÚfiÓÔ˘, ÂÓÒ Ë ¿ÏÈÔ˜ Ì¿˙· ·ÚÔ˘Û›·Û ÛÙ·ıÂÚ‹ ·‡ÍËÛË Î·È ÛÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ‰Â‡ÙÂÚÔ˘ ¯ÚfiÓÔ˘ (18). ŸÌˆ˜, ÌÂÙ¿ ·fi 2 ¯ÚfiÓÈ· ıÂڷ›·˜ Û ÌÂÁ¿ÏÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ, ·Ú¿ ÙË Ì›ˆÛË ÙÔ˘ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡, ‰ÂÓ ˘¿Ú¯Ô˘Ó ÛËÌ·ÓÙÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÙÔ˘ BMI (14). √È ‚·ÛÈΤ˜ ÂÓÂÚÁÂȷΤ˜ ‰·¿Ó˜, Ô˘ ‹Ù·Ó ÂÏ·Ùو̤Ó˜ ÚÔ ıÂڷ›·˜ Û˘ÁÎÚÈÙÈο ÌÂ Ê˘ÛÈÔÏÔÁÈο ·È‰È¿ Ì ÙËÓ ›‰È· ÂÈÊ¿ÓÂÈ· ÛÒÌ·ÙÔ˜, ·˘Í‹ıËÎ·Ó ÌÂÙ¿ ·fi ‰‡Ô ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛ˘ GH (18). ∏ Ì˘˚΋ ÈÛ¯‡˜ Î·È Ë ÎÈÓËÙÈÎfiÙËÙ· ·ÚÔ˘Û›·Û·Ó ›Û˘ ·‡ÍËÛË ÌÂÙ¿ ·fi ¤Ó· ¯ÚfiÓÔ ·ÁˆÁ‹˜, ÂÓÒ Ë ‚ÂÏÙ›ˆÛË ·˘Ù‹ ‰È·ÙËÚ‹ıËÎÂ Î·È ÛÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ‰Â‡ÙÂÚÔ˘ ¯ÚfiÓÔ˘ (18). ∂›Ó·È ÛËÌ·ÓÙÈÎfi fiÙÈ ÛÙËÓ ›‰È· ÌÂϤÙË ÔÈ ÁÔÓ›˜ ·Ó¤ÊÂÚ·Ó ·‡ÍËÛË Ù˘ Ê˘ÛÈ΋˜ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ ÙˆÓ ·È‰ÈÒÓ, Ù˘ ·ÓÙÔ¯‹˜ ÛÙËÓ ¿ÛÎËÛË Î·È Ù˘ ·fiÎÙËÛ˘ Ó¤ˆÓ ·‰ÚÒÓ ÎÈÓËÙÈÎÒÓ ‰ÂÍÈÔÙ‹ÙˆÓ (18). ∏ ‚ÂÏÙ›ˆÛË Ù˘ ۈ̷ÙÈ΋˜ Û‡ÛÙ·Û˘ Î·È ÙˆÓ ‚·ÛÈÎÒÓ ÂÓÂÚÁÂÈ·ÎÒÓ ‰··ÓÒÓ ÙÂÎÌËÚÈÒıËÎÂ Î·È Û ÂfiÌÂÓË ÌÂϤÙË (24). ¶ÚfiÛÊ·Ù·, Ë GH ¯ÔÚËÁ‹ıËÎÂ Î·È Û ÂÓ‹ÏÈΘ ·ÛıÂÓ›˜ Ì ÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi, Ì ¢ÓÔ˚ο ·ÔÙÂϤÛÌ·Ù· ˆ˜ ÚÔ˜ ÙË Û‡ÛÙ·ÛË ÛÒÌ·ÙÔ˜ ¯ˆÚ›˜ ÛËÌ·ÓÙÈΤ˜ ·ÚÂÓ¤ÚÁÂȘ (25,26,27). √ µªπ Î·È Ô ÏfiÁÔ˜ ̤Û˘ ÚÔ˜ ÁÔÊÔ‡˜ (W/∏) ‰ÂÓ ¿ÏÏ·Í ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜. H ¿ÏÈÔ˜ Ì¿˙· ·˘Í‹ıËÎÂ, Ô ÏÈ҉˘ ÈÛÙfi˜ ÌÂÈÒıËΠ(26,27) Î·È Ë ‚ÂÏÙ›ˆ-
ÛË Ù˘ ۈ̷ÙÈ΋˜ Û‡ÛÙ·Û˘ Û˘Ó¯›ÛÙËÎÂ, ÂÎÙfi˜ ·fi ÙÔÓ 1Ô ¯ÚfiÓÔ ıÂڷ›·˜, Î·È Î·Ù¿ Ù· ÂfiÌÂÓ· 4 ¯ÚfiÓÈ· Ù˘ ıÂڷ›·˜ (26). ∞ÎfiÌË, Ì ÙË ¯ÔÚ‹ÁËÛË Ù˘ GH ·ÔηٷÛÙ¿ıËÎ·Ó ÔÈ ‹È˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ı˘ÚÂÔÂȉÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ (¯·ÌËÏ¿ ›‰· T3) Ô˘ ·Ú·ÙËÚ‹ıËÎ·Ó Û ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi (27). ∏ ·ÔηٿÛÙ·ÛË Ù˘ ı˘ÚÂÔÂȉÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Â›Ó·È Èı·ÓfiÓ Ó· Û˘Ì‚¿ÏÏÂÈ ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ۈ̷ÙÈ΋˜ Û‡ÛÙ·Û˘ (27). ™˘ÓÔ„›˙ÔÓÙ·˜, Ë ıÂڷ›· Ì GH ÛÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi ‚ÂÏÙÈÒÓÂÈ ÙË ÛˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË, ·˘Í¿ÓÔÓÙ·˜ ÙËÓ ¿ÏÈÔ Ì¿˙·, ÌÂÈÒÓÔÓÙ·˜ ÙÔÓ ÏÈÒ‰Ë ÈÛÙfi Î·È ‚ÂÏÙÈÒÓÔÓÙ·˜ ÙȘ ÂÓÂÚÁÂȷΤ˜ ‰·¿Ó˜, ¯ˆÚ›˜ Ó· Âȉڿ ÛËÌ·ÓÙÈο ÛÙÔÓ BMI. ∏ ıÂڷ›· Ì GH ·ÔÎÏÂÈÛÙÈο Ê·›ÓÂÙ·È fiÙÈ ‰ÂÓ ÌÔÚ› Ó· ·ӷʤÚÂÈ ÙË ÛˆÌ·ÙÈ΋ Û‡ÛÙ·ÛË ÛÙ· Ê˘ÛÈÔÏÔÁÈο ›‰·. ÕÏϘ ÂȉڿÛÂȘ Ù˘ ıÂڷ›·˜ Ì GH AӷʤÚÂÙ·È fiÙÈ Ë ıÂڷ›· Ì GH ‚ÂÏÙÈÒÓÂÈ ÙËÓ ·Ó·Ó¢ÛÙÈ΋ ÏÂÈÙÔ˘ÚÁ›· Û ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi, Èı·ÓfiÓ ·˘Í¿ÓÔÓÙ·˜ ÙËÓ ÈÛ¯‡ ÙˆÓ ·Ó·Ó¢ÛÙÈÎÒÓ Ì˘ÒÓ (24,28). ∂ÈϤÔÓ ·Ú·ÙËÚ‹ıËΠ‚ÂÏÙ›ˆÛË ÙÔ˘ ·ÂÚÈÛÌÔ‡ Î·È Ù˘ ÂÈÛÓ¢ÛÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÌÂÙ¿ ·fi 6 Ì‹Ó˜ ıÂڷ›·˜ Ì GH, Èı·ÓfiÓ ÏfiÁˆ ÎÂÓÙÚÈ΋˜ ‰È¤ÁÂÚÛ˘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ ΤÓÙÚÔ˘ (29). ∂›Û˘, Ë ıÂڷ›· Ì GH Û Ôχ ÌÈÎÚ¿ ·È‰È¿ (<3 ¤ÙË) Ô‰ËÁ›, ÂÎÙfi˜ ·fi ‚ÂÏÙ›ˆÛË Ù˘ ·‡ÍËÛ˘ Î·È Ù˘ ۈ̷ÙÈ΋˜ Û‡ÛÙ·Û˘, Î·È Û ‚ÂÏÙ›ˆÛË Ù˘ ÁÏÒÛÛ·˜ Î·È Ù˘ ·ÓÙ›Ï˄˘ (Ì·ıËÛȷ΋˜ ÈηÓfiÙËÙ·˜), ÔfiÙ ›Ûˆ˜ Â›Ó·È ÚÔÙÈÌfiÙÂÚÔ Ë ·ÁˆÁ‹ Ó· ÍÂÎÈÓ¿ÂÈ Û Ôχ Ó·ڋ ËÏÈΛ· (30). ¶·ÚÂÓ¤ÚÁÂȘ Ù˘ ıÂڷ›·˜ Ì GH ™Â οÔȘ ÌÂϤÙ˜ (14,22), ·ÏÏ¿ fi¯È Û fiϘ (23), ·Ó·Ê¤ÚıËΠ·Ó¿Ù˘ÍË ·ıÔÏÔÁÈ΋˜ η̇Ï˘ ÁÏ˘Îfi˙˘ ‹/Î·È ‰È·‚‹ÙË Ù‡Ô˘ ππ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ Ì GH. ∏ ‰È·ÎÔ‹ Ù˘ GH Ô‰‹ÁËÛ Û ¿ÓÔ‰Ô Ù˘ ÁÏ˘Îfi˙˘ ÛÂ Ê˘ÛÈÔÏÔÁÈο ›‰· (22). ∏ ÈÔ Û˘¯Ó‹ ·ÚÂÓ¤ÚÁÂÈ· Ù˘ ıÂڷ›·˜ Ì G∏ ÛÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi Â›Ó·È Ë ÛÎÔÏ›ˆÛË, Ë ÔÔ›· fiÙ·Ó ÚÔ¸¿Ú¯ÂÈ ÌÔÚ› Ó· ÂȉÂÈÓˆı› (14). ∂›Û˘, ·Ó·Ê¤ÚÂÙ·È ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ·‰ÚÂÓ·Ú¯‹˜ Û ÔÛÔÛÙfi 57% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‹Ú·Ó ıÂڷ›· Ì GH (23). ™Â ¿ÙÔÌ· Ì ÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi Ù· ÔÔ›· ÂÏ¿Ì‚·Ó·Ó ıÂڷ›· Ì GH, ·Ó·Ê¤ÚıËÎ·Ó ·ÈÊÓ›‰ÈÔÈ ı¿Ó·ÙÔÈ, ΢ڛˆ˜ ·fi ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ Î·È ˘Ô·ÂÚÈÛÌfi ÛÙ· ·È‰È¿ Î·È ·fi ÙËÓ ·¯˘Û·ÚΛ· Î·È ÙȘ ÂÈÏÔΤ˜ Ù˘ ÛÙÔ˘˜ ÂÓ‹ÏÈΘ (31,32). ¶·Ú¿ ÙËÓ Â˘ÂÚÁÂÙÈ΋ ›‰Ú·ÛË Ù˘ GH ÛÙËÓ ·‡ÍËÛË, ÙË ¶·È‰È·ÙÚÈ΋ 2009;72:10-15
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·14
14
E. ∫Ô‡ÛÙ· Î·È Û˘Ó.
ۈ̷ÙÈ΋ Û‡ÛÙ·ÛË Î·È ÙË Ì·ıËÛȷ΋ ÈηÓfiÙËÙ·, ÔÈ ·Ú·ÙËÚ‹ÛÂȘ ·˘Ù¤˜ Ô‰‹ÁËÛ·Ó ÙÔ˘˜ ıÂÚ¿ÔÓÙ˜ ÁÈ·ÙÚÔ‡˜ Û ÛÎÂÙÈÎÈÛÌfi ˆ˜ ÚÔ˜ ÙË ¯Ú‹ÛË Ù˘ ηÈ, Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ, Û ‰È·ÎÔ‹ Ù˘ ıÂڷ›·˜. ∏ ¯ÔÚ‹ÁËÛË Ù˘ GH ‚ÂÏÙÈÒÓÂÈ ÙËÓ ·Ó·Ó¢ÛÙÈ΋ ÏÂÈÙÔ˘ÚÁ›· (24), fï˜ Â›Ó·È Èı·ÓfiÓ Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ (Û ·¯‡Û·Úη ¿ÙÔÌ· Î·È Û ¿ÙÔÌ· Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ¿ÓÔȘ ‡ÓÔ˘) Ó· ÂȉÂÈÓÒÓÂÈ ÙÔÓ ˘Ô·ÂÚÈÛÌfi Ì 3 Ì˯·ÓÈÛÌÔ‡˜: ·) Ô‰ËÁ› Û ·‡ÍËÛË ÙÔ˘ ÌÂÁ¤ıÔ˘˜ ÙÔ˘ Ì·Ï·ÎÔ‡ ÈÛÙÔ‡ ÙÔ˘ ·ÓÒÙÂÚÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ Î·È ˘ÂÚÙÚÔÊ›· ÙˆÓ ·‰ÂÓÔÂȉÒÓ Â΂ϷÛÙ‹ÛˆÓ, ‚) ·˘Í¿ÓÂÈ ÙÔÓ ‚·ÛÈÎfi ÌÂÙ·‚ÔÏÈÛÌfi ηÈ, Û˘ÓÂÒ˜, ÙËÓ Î·Ù·Ó¿ÏˆÛË Ô͢ÁfiÓÔ˘ Î·È Á) ·˘Í¿ÓÂÈ ÙÔÓ fiÁÎÔ ÙÔ˘ ·›Ì·ÙÔ˜ Î·È ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÚÔ¸¿Ú¯Ô˘Û· ·Ê˘‰¿ÙˆÛË (32). ¶ÚÔÙ›ÓÂÙ·È, ÏÔÈfiÓ, ÛÙ· ¿ÙÔÌ· Ì ÙÔ Û‡Ó‰ÚÔÌÔ Prader-Willi, ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ Ó· Ï·Ì‚¿ÓÂÙ·È ÈÛÙÔÚÈÎfi ÁÈ· ¿ÓÔȘ ‡ÓÔ˘ Î·È Ó· Á›ÓÂÙ·È ÚÔÛÂÎÙÈÎfi˜ ˆÙÔÚÈÓÔÏ·Ú˘ÁÁÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜, ¤ÏÂÁ¯Ô˜ ·Ó·Ó¢ÛÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È Ô͢ÌÂÙÚ›·, ÒÛÙ ӷ ÂÓÙÔÈÛÙÔ‡Ó Ù· ¿ÙÔÌ· Ô˘ ¤¯Ô˘Ó ˘„ËÏfi ΛӉ˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ·ÚÂÓÂÚÁÂÈÒÓ ·fi ÙË ıÂڷ›· (32). ∂ÈϤÔÓ, ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ Û˘ÓÈÛÙ¿Ù·È ·ÒÏÂÈ· ‚¿ÚÔ˘˜, ȉȷ›ÙÂÚ· ÛÙ· Ôχ ·¯‡Û·Úη ¿ÙÔÌ·, ÔÏ˘Î·Ù·ÁÚ·ÊÈ΋ ÌÂϤÙË ‡ÓÔ˘ (polysomnography) ÛÙ· ¿ÙÔÌ· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Î·È ·Ê·›ÚÂÛË ·‰ÂÓÔÂȉÒÓ Â΂ϷÛÙ‹ÛÂˆÓ fiÙ·Ó ˘¿Ú¯ÂÈ ˘ÂÚÙÚÔÊ›· (32). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ Û˘ÓÈÛÙ¿Ù·È Ù·ÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË Ô˘ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ Î·È ÙËÓ ÔÏ˘Î·Ù·ÁÚ·ÊÈ΋ ÌÂϤÙË ‡ÓÔ˘. ™Ù· ¿ÙÔÌ· Ì ¿ÓÔȘ ‡ÓÔ˘ ‰ÂÓ ·ÔÎÏ›ÂÙ·È Ë ¯Ú‹ÛË Ù˘ GH, ·ÊÔ‡ Á›ÓÂÈ ˘ÔÛÙ‹ÚÈÍË ÙÔ˘ ·ÂÚÈÛÌÔ‡. øÛÙfiÛÔ, ·Ó ·ÔÊ·ÛÈÛÙ› Ë ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜, Ú¤ÂÈ Ó· ˘¿Ú¯ÂÈ Ù·ÎÙÈ΋ Î·È Ôχ ÚÔÛÂÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË, Ì ÔÏ˘Î·Ù·ÁÚ·ÊÈ΋ ÌÂϤÙË ‡ÓÔ˘. §fiÁˆ ÙÔ˘ fiÙÈ Ù· ÂÚÈÛÛfiÙÂÚ· ÂÂÈÛfi‰È· (75%) ·ÈÊÓȉ›ˆÓ ı·Ó¿ÙˆÓ Û˘Ó¤‚ËÛ·Ó Î·Ù¿ ÙÔ˘˜ 9 ·Ú¯ÈÎÔ‡˜ Ì‹Ó˜ Ù˘ ıÂڷ›·˜ Ì GH, Û˘ÓÈÛÙ¿Ù·È Ó· ¯ÔÚËÁÂ›Ù·È Ë GH ·Ú¯Èο Û ÌÈÎÚ¤˜ ‰fiÛÂȘ, Ó· Á›ÓÂÙ·È ÛÙ·‰È·Î‹ ÙÈÙÏÔÔ›ËÛË Ù˘ ‰fiÛ˘ Î·È Ë ·Ú·ÎÔÏÔ‡ıËÛË Ó· Â›Ó·È Ù·ÎÙÈ΋ ÙÔ˘˜ ÚÒÙÔ˘˜ Ì‹Ó˜ Ù˘ ıÂڷ›·˜ (33).
™˘ÌÂÚ¿ÛÌ·Ù· ∏ ıÂڷ›· Ì GH ÛÙ· ·È‰È¿ Ì ۇӉÚÔÌÔ Prader-Willi ‚ÂÏÙÈÒÓÂÈ ÙÔ ‡„Ô˜, ÙÔÓ Ú˘ıÌfi ·Ó¿Ù˘Í˘ ηÈ, Èı·ÓfiÓ, ÙÔ ÙÂÏÈÎfi ·Ó¿ÛÙËÌ·. ∂›Û˘, Ë ıÂڷ›· ‚ÂÏÙÈÒÓÂÈ ÙË Û‡ÛÙ·ÛË ÛÒÌ·ÙÔ˜, ·˘Í¿ÓÔÓÙ·˜ ÙËÓ ¿ÏÈÔ Ì¿˙· Î·È ÌÂÈÒÓÔÓÙ·˜ ÙÔÓ ÏÈÒ‰Ë ÈÛÙfi, ¯ˆÚ›˜ fï˜ Ó· ‚ÂÏÙÈÒÓÂÈ ÛËÌ·ÓÙÈο ÙËÓ ·¯˘Û·ÚΛ·. ∏ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· Â›Ó·È Î·Ï‡ÙÂÚË fiÙ·Ó ÍÂÎÈÓ¿ Û ÌÈÎÚ‹ ËÏÈΛ·. ∂ÓÙÔ‡ÙÔȘ, ÙÔ ‡„Ô˜ Û¿ÓÈ· ·ÔÙÂÏ› ·ÚÈ· ·ÓËÛ˘¯›· ÛÙÔ Û‡Ó‰ÚÔÌÔ, ÏfiÁˆ ÙˆÓ ÔÏÏ·ÏÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ Ô˘ ·ÓÙÈÌÂÙˆ›Paediatriki 2009;72:10-15
˙Ô˘Ó Ù· ·È‰È¿ Î·È ÔÈ ÔÈÎÔÁ¤ÓÂȤ˜ ÙÔ˘˜. °È’ ·˘Ùfi, Ë ıÂڷ›· Ì GH ‰ÂÓ Û˘ÓÈÛÙ¿Ù·È ˆ˜ ‚·ÛÈ΋ Ú·ÎÙÈ΋ ÁÈ· ÙË ‚ÂÏÙ›ˆÛË Ù˘ ·‡ÍËÛ˘ ÙˆÓ ·È‰ÈÒÓ ·˘ÙÒÓ. ∏ ¯ÔÚ‹ÁËÛË GH ÌÔÚ› Ó· Â›Ó·È ¯Ú‹ÛÈÌË ˆ˜ ÚÔ˜ ÙËÓ ·‡ÍËÛË, Û ÂÚÈÙÒÛÂȘ Ô˘ ÙÔ ·È‰› ÂÌÊ·Ó›˙ÂÈ ¯·ÌËÏfi ·Ó¿ÛÙËÌ·, ÂÏ·Ùو̤ÓÔ Ú˘ıÌfi ·‡ÍËÛ˘ ÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ‚¿ÚÔ˜ Î·È ÚÔ¤Ú¯ÂÙ·È ·fi ÌÈ· ¢·ÈÛıËÙÔÔÈË̤ÓË ÔÈÎÔÁ¤ÓÂÈ·, ·fi ÙËÓ ÔÔ›· ·Ó·Ì¤ÓÂÙ·È Î·Ï‹ Û˘ÌÌfiÚʈÛË. ™˘ÓÈÛÙ¿Ù·È ·Ú¯È΋ ‰fiÛË 15IU(5mg)/m2/‚‰. ÂÚ›Ô˘, fiˆ˜ ÁÈ· ÙËÓ ÎÏ·ÛÈ΋ ·Ó¿ÚÎÂÈ· GH, Ì ·Ó·ÚÔÛ·ÚÌÔÁ‹ Ù˘ ‰fiÛ˘, Ì ‚¿ÛË ÙËÓ ·ÓÙ·fiÎÚÈÛË Ù˘ ·‡ÍËÛ˘ Î·È Ù· ›‰· ÙÔ˘ IGF-1. ∆· ÚfiÛÊ·Ù· ‰Â‰Ô̤ӷ Ô˘ ·ÊÔÚÔ‡Ó ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ۈ̷ÙÈ΋˜ Û‡ÛÙ·Û˘ ‰ÂÓ ÌÔÚÔ‡Ó Ó· Û˘ÓËÁÔÚ‹ÛÔ˘Ó Â·ÚÎÒ˜, ÙÔ˘Ï¿¯ÈÛÙÔÓ ÚÔ˜ ÙÔ ·ÚfiÓ, ˘¤Ú Ù˘ ÂÈÙ·ÎÙÈ΋˜ ¯ÔÚ‹ÁËÛ˘ GH ˆ˜ ıÂڷ›·˜ ÚÔ˘Ù›Ó·˜, ÂÓÒ Ô ‰È·ÙÚÔÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ ·Ú·Ì¤ÓÂÈ Ô ·ÎÚÔÁˆÓÈ·›Ô˜ Ï›ıÔ˜ Ù˘ ηϋ˜ ·ÓÙÈÌÂÙÒÈÛ˘. ∏ ‚ÂÏÙȈ̤ÓË Ì˘˚΋ ÈÛ¯‡˜ Î·È ÎÈÓËÙÈÎfiÙËÙ·, Ô˘ ÂÚÈÁÚ¿ÊÔÓÙ·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó ıÂڷ›· Ì GH (18,30), ¤¯ÂÈ È‰È·›ÙÂÚÔ ÂӉȷʤÚÔÓ ÁÈ· ÙË ıÂڷ›· ÙˆÓ ·È‰ÈÒÓ Ì ۇӉÚÔÌÔ Prader-Willi ÚÔÛ¯ÔÏÈ΋˜ ËÏÈΛ·˜. ∏ ‚ÂÏÙ›ˆÛË Ù˘ ۈ̷ÙÈ΋˜ Û‡ÛÙ·Û˘ Î·È Ù˘ Ì˘˚΋˜ Ì¿˙·˜ ÛÙËÓ ËÏÈÎȷ΋ ·˘Ù‹ ÔÌ¿‰· ı· ÌÔÚÔ‡Û ӷ ¤¯ÂÈ ÛËÌ·ÓÙÈ΋ ›‰Ú·ÛË ÛÙËÓ ÎÈÓËÙÈÎfiÙËÙ¿ ÙÔ˘˜, Ì ٷ¯‡ÙÂÚË Â›Ù¢ÍË ÙˆÓ ·‰ÚÒÓ ÎÈÓËÙÈÎÒÓ ÔÚfiÛË̈Ó, ηıÒ˜ Î·È ÁÂÓÈÎfiÙÂÚ· ÛÙËÓ ÔÈfiÙËÙ· ˙ˆ‹˜. √È ·ÈÊÓ›‰ÈÔÈ ı¿Ó·ÙÔÈ Ô˘ ·Ú·ÙËÚ‹ıËÎ·Ó Î˘Ú›ˆ˜ ·fi ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ Î·È ˘Ô·ÂÚÈÛÌfi ÛÙ· ·È‰È¿ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ Ì GH Ô‰ËÁÔ‡Ó Û ÚÔ‚ÏËÌ·ÙÈÛÌfi ˆ˜ ÚÔ˜ ÙËÓ ·ÛÊ¿ÏÂÈ· Ù˘ ıÂڷ›·˜. °È· Ó· ÂÓÙÔÈÛÙÔ‡Ó Ù· ¿ÙÔÌ· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Î·È Ó· ÚÔÏËÊı› Ù˘¯fiÓ Âȉ›ӈÛË ÙÔ˘ ˘Ô·ÂÚÈÛÌÔ‡ ηٿ ÙË ıÂڷ›· ¯ÚÂÈ¿˙ÂÙ·È ÚÔÛÂÎÙÈÎfi˜ ˆÙÔÚÈÓÔÏ·Ú˘ÁÁÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜, ¤ÏÂÁ¯Ô˜ ·Ó·Ó¢ÛÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È Ô͢ÌÂÙÚ›·, ÚÈÓ Î·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·ÒÏÂÈ· ‚¿ÚÔ˘˜, ÔÏ˘Î·Ù·ÁÚ·ÊÈ΋ ÌÂϤÙË ‡ÓÔ˘ Î·È ˘ÔÛÙ‹ÚÈÍË ÙÔ˘ ·ÂÚÈÛÌÔ‡, fiÔ˘ Â›Ó·È ··Ú·›ÙËÙÔ.
µÈ‚ÏÈÔÁÚ·Ê›· 1. Cassidy SB, Dykens E, Williams CA. Prader-Willi and Angelman syndromes: sister imprinted disorders. Am J Med Genet 2000;97:136-146. 2. Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 2004;15:12-20. 3. Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, et al. Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet 2008;40:719-721. 4. Donaldson MD, Chu CE, Cooke A, Wilson A, Greene SA,
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Stephenson JB. The Prader-Willi syndrome. Arch Dis Child 1994;70:58-63. 5. Burman P, Ritzén EM, Lindgren AC. Endocrine Dysfunction in Prader-Willi Syndrome: A Review with Special Reference to GH. Endocrine Reviews 2001;22: 787-799. 6. Donaldson MD. Natural history of Prader-Willi syndrome. Pharmacia International Growth Database Report No 20: Biannual Report, 2002. 7. Butler MG, Meaney FJ. Standards for selected anthropometric measurements in Prader-Willi syndrome. Pediatrics 1991;88:853-860. 8. Wollmann HA, Schultz U, Grauer ML, Ranke MB. Reference values for height and weight in Prader-Willi syndrome based on 315 patients. Eur J Pediatr 1998;157: 634-642. 9. Hauffa BP, Schlippe G, Roos M, Gillessen-Kaesbach G, Gasser T. Spontaneous growth in German children and adolescents with genetically confirmed Prader-Willi syndrome. Ada Paediatr 2000;89:1302-1311. 10. Brambilla P, Bosio L, Manzoni P, Pietrobelli A, Beccaria L, Chiumello G. Peculiar body composition in patients with Prader-Labhart-Willi syndrome. Am J Clin Nutr 1997;65: 1369-1374. 11. Schoeller DA, Levitsky LL, Bandini LG, Dietz WW, Walczak A. Energy expenditure and body composition in Prader-Wiili syndrome. Metabolism 1988;37:115-120. 12. Eiholzer U, Blum W, Molinari L. Body fat determined by skinfold measurements is elevated despite underweight in infants with Prader-Labhart-Willi syndrome. J Pediatr 1999;134:222-225. 13. Hoim VA, Pipes PL. Food and children with Prader-Willi syndrome. Am J Dis Child 1976;130:63-67. 14. Craig ME, Cowell CT, Larsson P, Craig ME, Cowell CT, Larsson P, et al. Growth hormone treatment and adverse events in Prader-Willi syndrome: data from KIGS (the Pfizer International Growth Database). Clin Endocrinol (Oxf) 2006;65:178-185. 15. Lindgren AC, Hagenäs L, Müller J, Blichfeldt S, Rosenborg M, Brismar T, et al. Effects of growth hormone treatment on growth and body composition in Prader-Willi syndrome: a preliminary report. Acta Paediatr Suppl 1997; 423:60-62. 16. Hauffa BP. One-year results of growth hormone treatment of short stature in Prader-Willi syndrome. Acta Paediatr Suppl 1997;423:63-65. 17. Davies PS, Evans S, Broomhead S, Clough H, Day JM, Laidlaw A, et al. Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome. Arch Dis Child 1998;78:474-476. 18. Myers SE, Carrel AL, Whitman BY, Allen DB. Sustained benefit after 2 years of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome. J Pediatr 2000;137: 42-49. 19. Tauber M, Barbeau C, Jouret B, Pienkowski C, Malzac P, Moncla A, et al. Auxological and endocrine evolution of 28 children with Prader-Willi syndrome: effect of GH therapy in 14 children. Horm Res 2000;53:279-287.
20. ∂iholzer U, L’Allemand D. Growth hormone normalizes height, prediction of final height and hand length in children with Prader-Willi syndrome after 4 years of therapy. Horm Res 2000;53:185-192. 21. Carrel AL, Myers SE, Whitman BY, Allen DB. Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study. J Clin Endocrinol Metab 2002;87:1581-1585. 22. Lindgren AC, Ritzen EM. Five years of growth hormone treatment in children with Prader Willi syndrome. Acta Paediatr Suppl 1999;88:109-111. 23. Angulo MA, Castro-Magana M, Lamerson M, Arguello R, Accacha S, Khan A. Final adult height in children with Prader-Willi syndrome with and without human growth hormone treatment. Am J Med Genet A 2007;143:14561461. 24. Haqq AM, Stadler DD, Jackson RH, Rosenfeld RG, Purnell JQ, LaFranchi SH. Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome. J Clin Endocrinol Metab 2003;88:2206-2212. 25. Höybye C, Hilding A, Jacobsson H, Thorén M. Growth hormone treatment improves body composition in adults with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2003;58:653-661. 26. Five-year growth hormone (GH) treatment in adults with Prader-Willi syndrome. Acta Paediatr 2007;96:410-413. 27. Mogul HR, Lee PD, Whitman BY, Zipf WB, Frey M, Myers S, et al. Growth hormone treatment of adults with PraderWilli syndrome and growth hormone deficiency improves lean body mass, fractional body fat, and serum triiodothyronine without glucose impairment: results from the United States multicenter trial. J Clin Endocrinol Metab 2008;93:1238-1245. 28. Carrel AL, Myers SE, Whitman BY, Allen DB. Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: a controlled study. J Pediatr 1999;134:215-221. 29. Lindgren AC, Hellström LG, Ritzén EM, Milerad J. Growth hormone treatment increases CO(2)-response, ventilation and central respiratory drive in children with Prader-Willi syndrome. Eur J Pediatr 1999;158:936-940. 30. Myers SE, Whitman BY, Carrel AL, Moerchen V, Bekx MT, Allen DB. Two years of growth hormone therapy in young children with Prader-Willi syndrome: physical and neurodevelopmental benefits. Am J Med Genet A 2007; 143:443-448. 31. Eiholzer U. Deaths in children with Prader-Willi syndrome. A contribution to the debate about the safety of growth hormone treatment in children with PWS. Horm Res 2005;63:33-39. 32. Stafler P, Wallis C. Prader-Willi syndrome: who can have growth hormone? Arch Dis Child 2008;93:341-345. 33. Tauber M, Diene G, Molinas C, Hébert M. Review of 64 cases of death in children with Prader-Willi syndrome (PWS). Am J Med Genet A 2008;146:881-887.
¶·È‰È·ÙÚÈ΋ 2009;72:10-15
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REVIEW ARTICLE
¡ÂÔÁÓÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi ‚-·ÈÌÔÏ˘ÙÈÎfi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ µ 1 µ’ ¡ÂÔÁÓÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞.¶.£., ¡ÔÛÔÎÔÌÂ›Ô ¶··ÁˆÚÁ›Ô˘, £ÂÛÛ·ÏÔÓ›ÎË 2 µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ∞.¶.£., ¡ÔÛÔÎÔÌÂ›Ô ∞Ã∂¶∞, £ÂÛÛ·ÏÔÓ›ÎË AÏÏËÏÔÁÚ·Ê›·: ÃÚ‹ÛÙÔ˜ ∆۷ηϛ‰Ë˜ zoichr@otenet.gr °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô £ÂÛÛ·ÏÔӛ΢ «¶··ÁˆÚÁ›Ô˘», £ÂÛÛ·ÏÔÓ›ÎË
Ã. ∆۷ηϛ‰Ë˜1, ∞. ∆Ú·ÁÈ·ÓÓ›‰Ë˜2, ¡. ¡ÈÎÔÏ·˝‰Ë˜1 ¶ÂÚ›ÏË„Ë: ∞Ó Î·È Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤¯ÂÈ Á›ÓÂÈ ÙÂÚ¿ÛÙÈ· ÚfiÔ‰Ô˜ ÛÙÔÓ ÙÔ̤· Ù˘ ÚfiÏ˄˘ Ù˘ ÓÂÔÁÓÈ΋˜ Ïԛ̈͢ ·fi ‚-·ÈÌÔÏ˘ÙÈÎfi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ µ (GBS), ÂÓÙÔ‡ÙÔȘ Ë Ïԛ̈ÍË ·˘Ù‹ ·Ú·Ì¤ÓÂÈ Ì›· ·fi ÙȘ ·ÚȘ ·Èٛ˜ ÛË„·ÈÌ›·˜ Î·È ÌËÓÈÁÁ›Ùȉ·˜ Û ·˘Ù‹ ÙËÓ ËÏÈΛ·. √ Á·ÛÙÚÂÓÙÂÚÈÎfi˜ ۈϋӷ˜ ·ÔÙÂÏ› ÙË Ê˘ÛÈ΋ ·ÓıÚÒÈÓË ‰ÂÍ·ÌÂÓ‹ ÁÈ· ÙÔÓ GBS Î·È ·Ó·ÁÓˆÚ›˙ÂÙ·È ˆ˜ Èı·Ó‹ ËÁ‹ ÁÈ· ÙÔÓ ÎÔÏÈÎfi ·ÔÈÎÈÛÌfi. ∏ ÓÂÔÁÓÈ΋ Ïԛ̈ÍË ·fi GBS ÚÔηÏÂ›Ù·È Û˘Ó‹ıˆ˜ ·fi ÙÔÓ ·ÔÈÎÈÛÌfi ÙÔ˘ ·ÌÓÈ·ÎÔ‡ ˘ÁÚÔ‡ ̤ۈ Ù˘ ·ÓÈÔ‡Û·˜ Ô‰Ô‡, Ô˘ Ô‰ËÁ› ÙÂÏÈο Û ÓfiÛÔ, Û ÌÂÚÈο ÓÂÔÁÓ¿. ŸÙ·Ó Ë Ïԛ̈ÍË Ï·Ì‚¿ÓÂÈ ¯ÒÚ· ÙȘ ÚÒÙ˜ 7 Ë̤Ú˜ Ù˘ ˙ˆ‹˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ˆ˜ ÚÒÈÌË, ÂÓÒ ÌÂÙ¿ ÙËÓ 7Ë Ë̤ڷ Î·È Ì¤¯ÚÈ ÙÔ˘˜ 3 Ì‹Ó˜ ˆ˜ fi„ÈÌË ÌÔÚÊ‹. ∏ Ó¢ÌÔÓ›· Î·È Ë ÛË„·ÈÌ›· ·ÔÙÂÏÔ‡Ó ÙȘ Û˘¯ÓfiÙÂÚ˜ ÂΉËÏÒÛÂȘ Ù˘ ÚÒÈÌ˘ ÌÔÚÊ‹˜, ÂÓÒ Ë Î‡ÚÈ· ÎÏÈÓÈ΋ ÂΉ‹ÏˆÛË Ù˘ fi„ÈÌ˘ Ïԛ̈͢ Â›Ó·È Ë ÌËÓÈÁÁ›Ùȉ·. ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ·Ó·ÛÎfiËÛ˘ Â›Ó·È Ë Â˘·ÈÛıËÙÔÔ›ËÛË ÙˆÓ ·È‰È¿ÙÚˆÓ Î·È ÙˆÓ ÓÂÔÁÓÔÏfiÁˆÓ ÛÙËÓ ·Ó·ÁÓÒÚÈÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘, ηıÒ˜ Î·È ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È ıÂڷ›·, Ô˘ ·ÔÙÂÏÔ‡Ó ··Ú·›ÙËÙ˜ ÚÔ¸Ôı¤ÛÂȘ ÁÈ· ÙËÓ ·ÔÙÚÔ‹ ÙˆÓ ÛÔ‚·ÚÒÓ ÂÈÏÔÎÒÓ Ù˘ ÓfiÛÔ˘. §¤ÍÂȘ ÎÏÂȉȿ: ™ÙÚÂÙfiÎÔÎÎÔ˜ ÔÌ¿‰·˜ µ, ÓÂÔÁÓÈ΋ ËÏÈΛ·, ÛË„·ÈÌ›·.
Newborn infections from group B Streptococcus 1 2nd Department of Neonatology, “Aristoteleio” University of Thessaloniki, “Papageorgiou” Hospital, Thessaloniki, Greece 2 2nd Department of Paediatrics, “Aristoteleio” University of Thessaloniki, “AHEPA” Hospital, Thessaloniki, Greece Correspondence: Christos Tsakalidis zoichr@otenet.gr “Papageorgiou” General Hospital of Thessaloniki, Thessaloniki, Greece
C. Tsakalidis1, A. Tragiannidis2, N. Nikolaidis1 Abstract: Even though great progress has been made in the prevention of neonatal Group B Streptococcus (GBS) infection, it remains one of the main causes of sepsis and meningitis at this age. The gastrointestinal tract represents the natural human source for GBS and constitutes a possible source of vaginal colonization. Neonatal GBS infection is due to the ascent of the bacteria into the amniotic fluid, which leads to neonatal colonization and subsequently to infection in some neonates. Early-onset disease occurs when the infection presents during the first 7 days of life, and late-onset disease presents after the 7th day and up to the 3rd month. Pneumonia and meningitis are the most common infections in neonates developing symptoms during the first 7 days of life, while the main clinical onset of late infection is meningitis. The aim of this review is to alert paediatricians and neonatologists to the risk factors, and to enable them to make timely diagnosis and initiation of treatment, which is necessary in order to avoid the serious consequences of the disease. Key words: Streptococcus group B, newborn, sepsis.
∂ÈÛ·ÁˆÁ‹ √ ‚-·ÈÌÔÏ˘ÙÈÎfi˜ ÛÙÚÂÙfiÎÔÎÎÔ˜ Ù˘ ÔÌ¿‰·˜ µ (Group B Streptococcus, GBS), ÁÓˆÛÙfi˜ Î·È ˆ˜ Streptococcus agalactiae, Â›Ó·È ¤Ó·˜ gramıÂÙÈÎfi˜ ‰ÈÏfiÎÔÎÎÔ˜, Ô ÔÔ›Ô˜ ·ÔÙÂÏ› Ì›· ·fi ÙȘ ÛËÌ·ÓÙÈÎfiÙÂÚ˜ ·Èٛ˜ Ù˘ ÓÂÔÁÓÈ΋˜ ÛË„·ÈÌ›·˜. ÀÔÏÔÁ›˙ÂÙ·È fiÙÈ ÛÙȘ ∏ӈ̤Ó˜ ¶ÔÏÈÙ›˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ 2.000 ÓÂÔÁÓ¿ ηٷϋÁÔ˘Ó Î¿ı ¯ÚfiÓÔ ·fi ÏÔÈÌÒÍÂȘ Ô˘ ÔÊ›ÏÔÓÙ·È ÛÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ‚·ÎÙ‹ÚÈÔ. ∞Ú¯Èο Ô GBS ÂÓÔ¯ÔÔÈ‹ıËΠÁÈ· ÙËÓ ÚfiÎÏËÛË Ù˘ Ì·ÛÙ›Ùȉ·˜ ÙˆÓ ‚ÔÔÂȉÒÓ Î·È Ô˘ÛÈ·ÛÙÈο ̤¯ÚÈ ÙÔ 1938 ‰ÂÓ ıˆÚ›ÙÔ ·ıÔÁfiÓÔ ÌÈÎÚfi‚ÈÔ ÁÈ· ÙÔÓ ·ÓıÚÒÈÓÔ ÔÚÁ·ÓÈÛÌfi (1,2). ŸÌˆ˜, ÛÙË ‰ÂηÂÙ›· ÙÔ˘ 1970 ·Ó·ÁÓˆÚ›˙ÂÙ·È ˆ˜ ¤Ó·˜ ÛËÌ·ÓÙÈÎfi˜ Paediatriki 2009;72:16-22
·ÈÙÈÔÏÔÁÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Ù˘ ÓÂÔÁÓÈ΋˜ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÛÈÌfiÙËÙ·˜, ÊÙ¿ÓÔÓÙ·˜ Û ˘„ËÏfiÙÂÚ· ÔÛÔÛÙ¿ ·ÎfiÌË Î·È ·fi ÙËÓ Escherichia coli, ÌÂ Û˘¯ÓfiÙËÙ· 2-3 ÂÚÈÙÒÛÂȘ ·Ó¿ 1000 ÁÂÓÓ‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ Î·È Ì ıÓËÛÈÌfiÙËÙ· ÂÚ›Ô˘ ÛÙÔ 50% ÙˆÓ ÂÚÈÙÒÛÂˆÓ (3). ™Ù· ÂfiÌÂÓ· ¯ÚfiÓÈ· ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈÎfiÙ·ÙË Ì›ˆÛË Ù˘ ıÓËÛÈÌfiÙËÙ·˜, Ë ÔÔ›· ·Ô‰›‰ÂÙ·È ÛÙËÓ ÂÈÛ·ÁˆÁ‹ Î·È ÂÊ·ÚÌÔÁ‹ ÙˆÓ ÂÚÈÁÂÓÓËÙÈÎÒÓ ÚÔÏËÙÈÎÒÓ Ì¤ÙÚˆÓ, ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ÓÂÔÁÓÈ΋˜ ÊÚÔÓÙ›‰·˜ Î·È ÛÙË ¯Ú‹ÛË ·ÓÙÈÌÈÎÚÔ‚È·ÎÒÓ Ê·Ú̿ΈÓ.
∂ȉËÌÈÔÏÔÁ›· ∆Ô Á·ÛÙÚÂÓÙÂÚÈÎfi Û‡ÛÙËÌ· Â›Ó·È Ë Ê˘ÛÈ΋
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·17
17
¡ÂÔÁÓÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi µ-·ÈÌÔÏ˘ÙÈÎfi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ µ
·ÓıÚÒÈÓË ‰ÂÍ·ÌÂÓ‹ ÁÈ· ÙÔÓ GBS Î·È ·ÔÙÂÏ› ÙËÓ Èı·Ó‹ ËÁ‹ ÁÈ· ÙÔÓ ÎÔÏÈÎfi ·ÔÈÎÈÛÌfi. ∏ ÌÂÙ·ÊÔÚ¿ ÙÔ˘ GBS ÛÙËÓ ¤ÁÎ˘Ô ÌÔÚ› Ó· Â›Ó·È ¯ÚfiÓÈ·, ‰È·ÏÂ›Ô˘Û· ‹ ·ÚÔ‰È΋ (4). ™Ù· ÓÂÔÁÓ¿ Ô˘ ÁÂÓÓÈÔ‡ÓÙ·È ·fi ÌËÙ¤Ú˜ ·ÔÈÎÈṲ̂Ó˜ Ì GBS, ÙÔ ÌÈÎÚfi‚ÈÔ ·ÔÌÔÓÒÓÂÙ·È ÛÙÔÓ ÚˆÎÙfi, ÛÙÔ ÔÌÊ·ÏÈÎfi ÎÔÏfi‚ˆÌ· ‹ ÛÙÔ ÛÙfiÌ·, Û ÔÛÔÛÙfi Ô˘ Î˘Ì·›ÓÂÙ·È ·fi 30-70%. Ÿˆ˜ ·Ó·Ê¤ÚıËÎÂ, ηٷÁÚ¿ÊÔÓÙ·È 2-3 ÂÚÈÙÒÛÂȘ ÓÂÔÁÓÈ΋˜ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢ ·Ó¿ 1.000 ÁÂÓÓ‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ, ·Ó Î·È Ë Â›ÙˆÛË ÌÔÚ› Ó· ·˘ÍËı› Û 10 ÂÚÈÛÙ·ÙÈο ·Ó¿ 1.000 ÁÂÓÓ‹ÛÂȘ Û ÂÚÈÔ¯¤˜ fiÔ˘ fiϘ ÔÈ ¤ÁÎ˘Â˜ Â›Ó·È ·ÔÎÈṲ̂Ó˜ Ì GBS (5-8). øÛÙfiÛÔ, ÌfiÓÔ 1-2% ÙˆÓ ÓÂÔÁÓÒÓ Ù· ÔÔ›· ÁÂÓÓ‹ıËÎ·Ó ·fi ÌËÙ¤Ú˜ ÊÔÚ›˜ ÂΉËÏÒÓÔ˘Ó ÎÏÈÓÈ΋ ÓfiÛÔ. √ ÏfiÁÔ˜ ÁÈ’ ·˘Ùfi ÙÔ ¯·ÌËÏfi ÔÛÔÛÙfi ·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙÔ˜ Î·È Â›Ó·È ·ÎfiÌË ˘fi ‰ÈÂÚ‡ÓËÛË. ¶Èı·ÓÔÏÔÁÂ›Ù·È Û˘Û¯¤ÙÈÛË ÌÂٷ͇ ÙÔ˘ ‚·ıÌÔ‡ ÌËÙÚÈÎÔ‡ ·ÔÈÎÈÛÌÔ‡ Î·È Ù˘ ÌÂÙ¤ÂÈÙ· ÎÏÈÓÈ΋˜ ÔÚ›·˜ ÙˆÓ ÓÂÔÁÓÒÓ. ∆· ÚfiˆÚ· ÓÂÔÁÓ¿ ¤¯Ô˘Ó 15 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚÔ Î›Ó‰˘ÓÔ Ó· ·Ó·Ù‡ÍÔ˘Ó ÛÙÚÂÙÔÎÔÎÎÈ΋ Ïԛ̈ÍË Û ۯ¤ÛË Ì ٷ ÙÂÏÂÈfiÌËÓ· Î·È ·˘Ùfi ÙÔ Ôχ ˘„ËÏfi ÔÛÔÛÙfi Ïԛ̈͢ ›Ûˆ˜ Ó· ·ÓÙ·Ó·ÎÏ¿ ÙÔ ·ÓÒÚÈÌÔ ·Ì˘ÓÙÈÎfi Û‡ÛÙËÌ¿ ÙÔ˘˜ (9). §fiÁˆ Ù˘ ÂÏ·Ùو̤Ó˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ·fi ÙÔÓ GBS, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ ·ÚÔ˘Û›· ο„·˜ ÛÙÔ ÂÓ ÏfiÁˆ ‚·ÎÙ‹ÚÈÔ, Ô ÚfiÏÔ˜ ÙˆÓ ÂȉÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ˆ˜ ·¿ÓÙËÛË ÛÙË Ïԛ̈ÍË Â›Ó·È ÎÚ›ÛÈÌ˘ ÛËÌ·Û›·˜. Œ¯ÂÈ ·Ô‰Âȯı› fiÙÈ ÙÔ 60% Ù˘ ‰È·Ï·ÎÔ˘ÓÙȷ΋˜ ÌÂÙ·ÊÔÚ¿˜ ÙˆÓ IgG ·ÓÙÈÛˆÌ¿ÙˆÓ Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Î˘Ú›ˆ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÙÚ›ÙÔ˘ ÙÚÈÌ‹ÓÔ˘ Ù˘ ·ËÛ˘ Î·È ÂȉÈÎfiÙÂÚ· ÌÂÙ¿ ÙËÓ 32Ë Â‚‰ÔÌ¿‰·, Ì ·ÔÙ¤ÏÂÛÌ· Ù· ÚfiˆÚ· ÓÂÔÁÓ¿ Ó· ¤¯Ô˘Ó ÂÏ¿¯ÈÛÙÔ˘˜ ‹ ¯·ÌËÏÔ‡˜ Ù›ÙÏÔ˘˜ ÌËÙÚÈÎÒÓ IgG ·ÓÙÈÛˆÌ¿ÙˆÓ (10). ™·ÊÒ˜ Ë ¯·ÌËÏ‹ ·ÓÙÈۈ̷ÙÈ΋ Û˘ÁΤÓÙÚˆÛË ·ÔÙÂÏ› ·ÈÙÈÔÏÔÁÈÎfi Î·È ÚԉȷıÂÛÈÎfi ·Ú¿ÁÔÓÙ· Ïԛ̈͢ ·fi GBS, fï˜ ‰ÂÓ Â›Ó·È Ô ÌÔÓ·‰ÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Î·È ·˘Ùfi ·Ô‰ÂÈÎÓ‡ÂÙ·È ·fi ÙËÓ ÂÚÁ·ÛÙËÚȷ΋ ·Ú·Ù‹ÚËÛË fiÙÈ Ù· ÂÚÈÛÛfiÙÂÚ· ÓÂÔÁÓ¿ Ô˘ ÁÂÓÓÈÔ‡ÓÙ·È ·fi ·ÔÈÎÈṲ̂Ó˜ ÌËÙ¤Ú˜ Î·È ¤¯Ô˘Ó ¯·ÌËÏ‹ ·ÚÔ˘Û›· ·ÓÙÈÛˆÌ¿ÙˆÓ ‰ÂÓ ÓÔÛÔ‡Ó (11). ∏ ÂÈÎÚ¿ÙËÛË ÙÔ˘ GBS, fiÛÔÓ ·ÊÔÚ¿ ÙÔÓ ·ÔÈÎÈÛÌfi ÛÙÔÓ ÎfiÏÔ Î·È ÛÙÔÓ ÚˆÎÙfi ÙˆÓ ÂÁ·ˆÓ Á˘Ó·ÈÎÒÓ, ÔÈΛÏÏÂÈ ÌÂٷ͇ ÙˆÓ ÂıÓÈÎÒÓ ÔÌ¿‰ˆÓ Î·È ÙˆÓ ÁˆÁÚ·ÊÈÎÒÓ ÂÚÈÔ¯ÒÓ, ηٿ ÚÔÛ¤ÁÁÈÛË ÌÂٷ͇ 10-40% (7,12-15). √È Á˘Ó·›Î˜ Ô˘ ·Ó‹ÎÔ˘Ó ÛÙË Ì·‡ÚË Ê˘Ï‹ ·Ó·Ê¤ÚÂÙ·È fiÙÈ ·ÔÈΛ˙ÔÓÙ·È Û ˘„ËÏfiÙÂÚÔ ÔÛÔÛÙfi Û ۇÁÎÚÈÛË Ì ÙȘ ˘fiÏÔȘ Ê˘ÏÂÙÈΤ˜ ÔÌ¿‰Â˜ (16). ∞Ó Î·È Ô ·ÔÈÎÈÛÌfi˜ Ì GBS ‰ÂÓ Û˘Ó‰¤ÂÙ·È Ì ÓfiÛËÛË Û ˘ÁÈ›˜ Á˘Ó·›Î˜, ÂÓÙÔ‡ÙÔȘ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÌfiÏ˘ÓÛË ÛÙËÓ ÂÁ΢ÌÔÛ‡ÓË. §ÔÈÌÒÍÂȘ ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡ ·fi GBS ¤¯Ô˘Ó ·-
Ú·ÙËÚËı› Û 2-4% ÙˆÓ Î˘‹ÛÂˆÓ (17). ™ÙȘ ›ÙÔΘ, ¿ÏϘ ÏÔÈÌÒÍÂȘ Ô˘ ÔÊ›ÏÔÓÙ·È Û GBS Â›Ó·È Ë ÛË„·ÈÌ›·, Ë ·ÌÓÈÔÓ›Ùȉ·, Ë ÂÓ‰ÔÌËÙÚ›Ùȉ· Î·È Û¿ÓÈ· Ë ÌËÓÈÁÁ›Ùȉ· (18). ∞fi ÙÔ˘˜ ÔÚfiÙ˘Ô˘˜ ÙÔ˘ GBS Ô˘ ¤¯Ô˘Ó ·Ó·ÁÓˆÚÈÛÙ›, ˘Â‡ı˘ÓÔÈ ÁÈ· ÏÔÈÌÒÍÂȘ Â›Ó·È Ô Ù‡Ô˜ Ia, Ô Ù‡Ô˜ Ib, Ô Ù‡Ô˜ ππ, Ô Ù‡Ô˜ πππ Î·È ÙÂÏÂ˘Ù·›· Ô Ù‡Ô˜ V. ∞Ó Î·È Ô ÏËı˘ÛÌfi˜ ÙˆÓ ÌÈÎÚÔ‚›ˆÓ ÛÙȘ ·ÔÈÎÈṲ̂Ó˜ Á˘Ó·›Î˜ ·ÚÔ˘ÛÈ¿˙ÂÈ ›ÛË Î·Ù·ÓÔÌ‹ fiÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ÙÚÂȘ ÈÔ ÎÔÈÓÔ‡˜ ÔÚfiÙ˘Ô˘˜ (π, ππ Î·È πππ), ÔÈ ÌÂϤÙ˜ ÛÙ· ÓÂÔÁÓ¿ Ì Ïԛ̈ÍË ‰Â›¯ÓÔ˘Ó ˘ÂÚÔ¯‹ ÙÔ˘ ÔÚfiÙ˘Ô˘ πππ (85%). ¶Èı·ÓÔ› ·Ú¿ÁÔÓÙ˜ Ô˘ ¢ı‡ÓÔÓÙ·È ÁÈ’ ·˘Ùfi Â›Ó·È Ë ·˘ÍË̤ÓË ·Ú·ÁˆÁ‹ ÂȉÈÎÔ‡ ·ÓÙÈÁfiÓÔ˘ Î·È Ë ÌÂÁ·Ï‡ÙÂÚË ·Ú·ÁˆÁ‹ Ó¢ڷÌÈÓȉ¿Û˘ (19).
¶·ıÔÁ¤ÓÂÈ· ∏ ÈÔ Û˘¯Ó‹ ÌÔÚÊ‹, Ë ÔÔ›· Ù·˘Ùfi¯ÚÔÓ· ¤¯ÂÈ Î·È ÙËÓ Î·Ï‡ÙÂÚË ÚfiÁÓˆÛË, Â›Ó·È Ë ÚÒÈÌË, ηٿ ÙËÓ ÔÔ›· Ë ÂΉ‹ÏˆÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Á›ÓÂÙ·È Ì¤Û· ÛÙȘ ÚÒÙ˜ 7 Ë̤Ú˜ ·fi ÙË Á¤ÓÓËÛË. ™˘¯ÓfiÙÂÚ· Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÂΉËÏÒÓÂÙ·È Ì¤Û· ÛÙȘ ÚÒÙ˜ 24 ÒÚ˜. ™ÙËÓ ÚÒÈÌË ÌÔÚÊ‹ ¤¯Ô˘Ì ›ÛË Â›ÙˆÛË Ù˘ ÓfiÛÔ˘ Û ¿ÚÚÂÓ· Î·È ı‹Ï·. Ÿˆ˜ ηٷ‰ÂÈÎÓ‡ÂÙ·È ·fi ÌÂϤÙË ÙˆÓ ÔÚfiÙ˘ˆÓ ·ÔÈÎÈÛÌ¤ÓˆÓ ÌËÙ¤ÚˆÓ Î·È ÓÂÔÁÓÒÓ, Ë ÌÂÙ¿‰ÔÛË Â›Ó·È Î¿ıÂÙË fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÚÒÈÌË ÓfiÛÔ. ™‡Ìʈӷ Ì ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ, ¤¯Ô˘Ó ηٷÁÚ·Ê› ‰‡Ô ÌÔÓ٤Ϸ ÌÂÙ¿‰ÔÛ˘ Ù˘ ÓfiÛÔ˘ ·fi ÙË ÌËÙ¤Ú· ÛÙÔ ÓÂÔÁÓfi. ™ÙÔ ÚÒÙÔ, ÙÔ ÓÂÔÁÓfi ÁÂÓÓÈ¤Ù·È Ì ¯·ÌËÏfi Apgar score Î·È ·ÎÔÏÔ˘ı› Ë Ó¢ÌÔÓÈ΋ ‰È‹ıËÛË, ÂÓÒ ÛÙÔ ‰Â‡ÙÂÚÔ ÙÔ ÓÂÔÁÓfi ÁÂÓÓÈ¤Ù·È ˘ÁȤ˜, ·ÏÏ¿ ·Ó·Ù‡ÛÛÂÈ ‚·ıÌÈ·›· Û˘ÌÙÒÌ·Ù· ·ÚÎÂÙ¤˜ Ë̤Ú˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË. ∞˘Ù‹ Ë ‰È·ÊÔÚ¿ Ô‰ËÁ› ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Ë Ïԛ̈ÍË ÌÔÚ› Ó· Û˘Ì‚Â› ›Ù ‰È·ÌÓȷο, ›Ù ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ‰Èfi‰Ô˘ ̤ۈ ÙÔ˘ ˘ÂÏÔÁÂÓÓËÙÈÎÔ‡ ۈϋӷ Ù˘ ÌËÙ¤Ú·˜. ™Â Ì›· ÌÂϤÙË ÙÔ˘ Garland, ÙÔ 56% ÙˆÓ ÓÂÔÁÓÒÓ Ì Ïԛ̈ÍË ·fi GBS ‹Ù·Ó Û˘Ìو̷ÙÈÎfi ηٿ ÙË Á¤ÓÓËÛË ‹ ̤۷ ÛÙȘ ÚÒÙ˜ 6 ÒÚ˜, ÁÂÁÔÓfi˜ Ô˘ ·Ô‰ÂÈÎÓ‡ÂÈ fiÙÈ Ë ÂÓ‰ÔÌ‹ÙÚÈ· Ïԛ̈ÍË ÌÔÚ› Ó· Â›Ó·È ˘Â‡ı˘ÓË ÁÈ· ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ÛÙÚÂÙÔÎÔÎÎÈÎÒÓ ÏÔÈÌÒÍÂˆÓ ÚÒÈÌ˘ ÌÔÚÊ‹˜ (20). ∫ÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ∏ Û˘¯ÓfiÙËÙ· Ù˘ ÊÔÚ›·˜ ÙÔ˘ GBS ÛÙËÓ ∂ÏÏ¿‰· Î˘Ì·›ÓÂÙ·È ÂÚ›Ô˘ ÛÙÔ 6,6% Î·È ·fi Ù· ÛÙÔȯ›· Ô˘ ÚÔ·ÙÔ˘Ó ·fi ÌÈ· ÙÂÏÂ˘Ù·›· ·Ó¿Ï˘ÛË, fiÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ÔÚfiÙ˘Ô˘˜, ¤¯Ô˘Ì ٷ ÂÍ‹˜ ÔÛÔÛÙ¿: ÔÚfiÙ˘Ô˜ Ia 19%, ÔÚfiÙ˘Ô˜ Ib 12%, ÔÚfiÙ˘Ô˜ ππ 26,9%, ÔÚfiÙ˘Ô˜ πππ 22,4% Î·È ÔÚfiÙ˘Ô˜ V 9% (21). ∏ Ïԛ̈ÍË ·fi GBS ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· ÌÔÚ› Ó· ÂΉËψı› ›Ù Ì ÙËÓ ÚÒÈÌË Â›Ù Ì ÙËÓ fi„ÈÌË ¶·È‰È·ÙÚÈ΋ 2009;72:16-22
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·18
18
Ã. ∆۷ηϛ‰Ë˜ Î·È Û˘Ó.
ÌÔÚÊ‹. ∆· ÓÂÔÁÓ¿ Ì Ïԛ̈ÍË ·fi GBS Û˘Ó‹ıˆ˜ ÂÌÊ·Ó›˙Ô˘Ó ÛË„·ÈÌ›· ‹ Ó¢ÌÔÓ›·, ˆÛÙfiÛÔ ÏÈÁfiÙÂÚÔ Û˘¯Ó¿ ÌÔÚ› Ó· ÂΉËÏÒÛÔ˘Ó ÌËÓÈÁÁ›Ùȉ·, ÔÛÙÂÔÌ˘ÂÏ›Ùȉ· ‹ ÛËÙÈ΋ ·ÚıÚ›Ùȉ·. ∏ ÛË„·ÈÌ›· Ì ‹ ¯ˆÚ›˜ Ó¢ÌÔÓ›·, ·ÔÙÂÏ› ÙËÓ Î‡ÚÈ· ÂΉ‹ÏˆÛË Ù˘ ÓfiÛÔ˘ Î·È ·Ú·ÙËÚÂ›Ù·È ÛÙÔ 90% ÙˆÓ ÂÚÈÙÒÛˆÓ, ÂÓÒ Ë ÌËÓÈÁÁ›Ùȉ· ÂÌÊ·Ó›˙ÂÙ·È ÂÚ›Ô˘ ÛÙÔ 10% (22). ŸÛÔÓ ·ÊÔÚ¿ Ù· ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο Ù˘ ÚÒÈÌ˘ ÓÂÔÁÓÈ΋˜ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢, ¤¯Ô˘Ì ÁÂÓÈο ÛËÌ›· ‹ Î·È Î·Ù·ÛÙÚÔÊÈΤ˜ ÌÔÚʤ˜ ÛË„·ÈÌ›·˜ Ì ˆ¯ÚfiÙËÙ·, shock, ˘ÔıÂÚÌ›· ‹ ˘ÂÚıÂÚÌ›·, ÔÈΛÏÔ˘ ‚·ıÌÔ‡ ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· Ì ·˘ÍË̤Ó˜ ··ÈÙ‹ÛÂȘ Û Ô͢ÁfiÓÔ, Ó¢ÌÔÓ›·, Û˘¯Ó¿ ·Ú·Ì¤ÓÔ˘Û· Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË Î·È ÌËÓÈÁÁ›Ùȉ·, Ô˘ Û ÔÚÈṲ̂Ó˜ ÌÂϤÙ˜ ÊÙ¿ÓÂÈ ÛÙÔ 30%. ∞fi Ù· ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ¤¯Ô˘Ì ˘ÔÁÏ˘Î·ÈÌ›·, Ï¢ÎÔ΢ÙÙ¿ÚˆÛË ‹ Ï¢ÎÔÂÓ›· Î·È ·˘ÍË̤ÓË Û¯¤ÛË ¿ˆÚˆÓ ÚÔ˜ ÒÚÈÌˆÓ ÔÏ˘ÌÔÚÊÔ‡ÚËÓˆÓ (5,6,15). ∏ fi„ÈÌË ÌÔÚÊ‹ Ù˘ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢ ÂÌÊ·Ó›˙ÂÙ·È ÌÂÙ¿ ÙËÓ ÚÒÙË Â‚‰ÔÌ¿‰· Ù˘ ˙ˆ‹˜ Î·È Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 3 ÌËÓÒÓ. ™’ ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË, Ô ÛÙÚÂÙfiÎÔÎÎÔ˜ ÌÔÚ› Ó· ÚÔ¤Ú¯ÂÙ·È Î·È ·fi ÌË ÌËÙÚÈ΋ ËÁ‹. À¿Ú¯ÂÈ ÌÂϤÙË fiÔ˘ ·fi ÙȘ 21 ÂÚÈÙÒÛÂȘ ÓÂÔÁÓÒÓ Ì fi„ÈÌË ÓfiÛÔ, ÌfiÓÔ Û 7 ÓÂÔÁÓ¿ ÔÈ ÌËÙ¤Ú˜ ›¯·Ó ·ÓȯÓ‡ÛÈ̘ ·ÔÈ˘ ÙÔ˘ ‚·ÎÙËÚȉ›Ô˘ ηٿ ÙÔÓ ÙÔÎÂÙfi, ÂÓÒ ÛÙ· ˘fiÏÔÈ· 14 ‰ÂÓ ·ÓȯÓ‡ıËÎ·Ó ·ÔÈ˘ (23). ∏ ÚÒÈÌË ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ ÚÔηÏÂ›Ù·È ·fi ¿ÓÔ‰Ô ÙÔ˘ GBS ÛÙÔ ·ÌÓÈ·Îfi ˘ÁÚfi, Ë ÔÔ›· Ô‰ËÁ› Û ·ÔÈÎÈÛÌfi ÙÔ˘ ÓÂÔÁÓÔ‡ Î·È ÛÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÓfiÛÔ˘ (24). ∏ ÂÚÈÁÂÓÓËÙÈ΋ ÌÂÙ¿‰ÔÛË ÙÔ˘ ÌÈÎÚÔ‚›Ô˘ ÌÔÚ› Ó· Á›ÓÂÈ ‰È· ̤ÛÔ˘ ›Ù ÂÚÚËÁÌ¤ÓˆÓ Â›Ù ¿ıÈÎÙˆÓ ÂÌ‚Ú˘˚ÎÒÓ ˘Ì¤ÓˆÓ (25). ™ÙËÓ fi„ÈÌË ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘, ÙÔ ÈÔ Û˘¯Ófi ¯·Ú·ÎÙËÚÈÛÙÈÎfi Â›Ó·È Ë ÌËÓÈÁÁ›Ùȉ·, Ë ÔÔ›· ηٷÏ›ÂÈ ÌfiÓÈÌ· Ó¢ÚÔÏÔÁÈο ˘ÔÏ›ÌÌ·Ù· Û ÔÛÔÛÙfi 50%. ∏ ÌËÓÈÁÁ›Ùȉ· ÂÌÊ·Ó›˙ÂÙ·È Û Ôχ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ÛÙËÓ fi„ÈÌË ÛË„·ÈÌ›· Û ۯ¤ÛË Ì ÙËÓ ÚÒÈÌË Î·È ·˘Ùfi ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ô Î›Ó‰˘ÓÔ˜ ÁÈ· Ó¢ÚÔÏÔÁÈο ˘ÔÏ›ÌÌ·Ù· Ó· Â›Ó·È ÌÂÁ·Ï‡ÙÂÚÔ˜ ÛÙËÓ fi„ÈÌË. ∏ ÚfiÁÓˆÛË ÙˆÓ ÓÂÔÁÓÒÓ Ì ÛË„·ÈÌ›· ·fi GBS ¤¯ÂÈ ‚ÂÏÙȈı› ÛËÌ·ÓÙÈο Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·. ¡ÂÔÁÓ¿ Ì ËÏÈΛ· ·ËÛ˘ ≥37 ‚‰ÔÌ¿‰Â˜ ÂÈ‚ÈÒÓÔ˘Ó Û ÔÛÔÛÙfi 98%, ÂÓÒ ÓÂÔÁÓ¿ Ì ËÏÈΛ· ·ËÛ˘ 34-36 ‚‰ÔÌ¿‰Â˜ ÂÈ‚ÈÒÓÔ˘Ó Û ÔÛÔÛÙfi 90%. ŸÛÔÓ ·ÊÔÚ¿ ÓÂÔÁÓ¿ Ì ÌÈÎÚfiÙÂÚË ËÏÈΛ· ·ËÛ˘ (≤33 ‚‰ÔÌ¿‰Â˜), Ë ÂÈ‚›ˆÛË ÏËÛÈ¿˙ÂÈ ÙÔ 70% (26).
¢È¿ÁÓˆÛË ∏ ηÏÏȤÚÁÂÈ· ·›Ì·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ ÈÔ ·ÍÈfiÈÛÙË Ì¤ıÔ‰Ô ÁÈ· ÙË ‰È¿ÁÓˆÛË Ù˘ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢. ∆Ô ÌfiÓÔ ÌÂÈÔÓ¤ÎÙËÌ· Ô˘ ·ÚÔ˘ÛÈ¿˙ÂÈ Paediatriki 2009;72:16-22
Â›Ó·È ÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·, ‰ÈfiÙÈ ¯ÚÂÈ¿˙ÂÙ·È Ó· ÌÂÛÔÏ·‚‹ÛÔ˘Ó 24-48 ÒÚ˜ ̤¯ÚÈ Ó· Á›ÓÔ˘Ó ÁÓˆÛÙ¿ Ù· ·ÔÙÂϤÛÌ·Ù·. ∏ ηٿ gram ¯ÚÒÛË ‰ÂÓ Â›Ó·È Â·ÚÎÒ˜ ¢·›ÛıËÙË Ì¤ıÔ‰Ô˜ ÁÈ· Ù·¯Â›· ·Ó›¯Ó¢ÛË ÙÔ˘ GBS. ¢È·ÁÓˆÛÙÈο test ÁÈ· ÙËÓ ¿ÌÂÛË Ù·˘ÙÔÔ›ËÛË ÙÔ˘ ÔÏ˘Û·Î¯·ÚȉÈÎÔ‡ ·ÓÙÈÁfiÓÔ˘ ÙÔ˘ GBS, fiˆ˜ Ë Ì¤ıÔ‰Ô˜ Û˘ÁÎfiÏÏËÛ˘ Ì latex Î·È Ë ELISA, ¤¯Ô˘Ó ÌÈÎÚfiÙÂÚË Â˘·ÈÛıËÛ›· Û ۇÁÎÚÈÛË Ì ٷ ·ÓÙ›ÛÙÔȯ· ÙˆÓ Î·ÏÏÈÂÚÁÂÈÒÓ (27). ¶ÚfiÛÊ·Ù·, Ë PCR ¤¯ÂÈ ‰Â›ÍÂÈ ÂÍ·ÈÚÂÙÈο ·ÔÙÂϤÛÌ·Ù·, Ì ¢·ÈÛıËÛ›· Ù˘ Ù¿Í˘ ÙÔ˘ 97% Î·È Û ۇÁÎÚÈÛË Ì ٷ ·ÔÙÂϤÛÌ·Ù· ÙˆÓ Î·ÏÏÈÂÚÁÂÈÒÓ ·›Ì·ÙÔ˜, ÂÓÒ Ô ·Ó·ÊÂÚfiÌÂÓÔ˜ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¯ÚfiÓÔ˜ Î˘Ì·›ÓÂÙ·È ·Ô 40-100 ÏÂÙ¿. ∞˘Ùfi Â›Ó·È ¤Ó· Ôχ ÛËÌ·ÓÙÈÎfi ÛÙÔȯ›Ô, ÙÔ ÔÔ›Ô ÌÔÚ›, ÌÂÏÏÔÓÙÈο, Ó· ·ÏÏ¿ÍÂÈ ÚÈ˙Èο ÙËÓ ÔÏÈÙÈ΋ ÙÔ˘ ÂϤÁ¯Ô˘ ÙˆÓ ÂÁ·ˆÓ Á˘Ó·ÈÎÒÓ fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÊÔÚ›· ÙÔ˘ GBS (28-32).
¶ÚfiÏË„Ë ∏ Ïԛ̈ÍË ·fi GBS ÚÔηÏ› ÛÔ‚·Ú‹ ÓfiÛÔ ÛÙ· ÓÂÔÁÓ¿ Î·È ÙÔ ÂӉȷʤÚÔÓ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÂÈÎÂÓÙÚÒÓÂÙ·È Î˘Ú›ˆ˜ ÛÙË Ï‹„Ë ÚÔÊ˘Ï·ÎÙÈÎÒÓ Ì¤ÙÚˆÓ ÁÈ· ÙËÓ ÚfiÏË„Ë Ù˘ Ïԛ̈͢ ·fi ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ÌÈÎÚfi‚ÈÔ. ∆Ô 1996 Î·È ÙÔ 1997, ÙÔ ∞ÌÂÚÈηÓÈÎfi ∫ÔϤÁÈÔ ª·È¢ÙÈ΋˜ Î·È °˘Ó·ÈÎÔÏÔÁ›·˜, ÙÔ ∫¤ÓÙÚÔ ÁÈ· ÙËÓ ¶ÚfiÏË„Ë Î·È ÙÔÓ ŒÏÂÁ¯Ô ÙˆÓ §ÔÈÌÒÍÂˆÓ Î·È Ë ∞ÌÂÚÈηÓÈ΋ ∞η‰ËÌ›· ¶·È‰È·ÙÚÈ΋˜ Âͤ‰ˆÛ·Ó Ô‰ËÁ›Â˜ ÁÈ· ÙËÓ ÚfiÏË„Ë Ù˘ Ïԛ̈͢ ·fi GBS (33-35). √È Û˘ÛÙ¿ÛÂȘ ·ÊÔÚÔ‡Û·Ó ÙÔÓ ¤ÏÂÁ¯Ô ÁÈ· ·ÔÈÎÈÛÌfi Ì GBS ÙˆÓ ÂÈÙfiÎˆÓ ‹ ÙËÓ ÚÔÛ¤ÁÁÈÛË Ì ‚¿ÛË ÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÂÌÊ¿ÓÈÛ˘ Ù˘ Ïԛ̈͢. ™‡Ìʈӷ Ì’ ·˘Ù¤˜ ÙȘ Ô‰ËÁ›Â˜, fiϘ ÔÈ Â›ÙÔΘ ÌÂٷ͇ 35˘ Î·È 37˘ ‚‰ÔÌ¿‰·˜ ·ËÛ˘ ÂϤÁ¯ÔÓÙ·È ÁÈ· ·ÔÈÎÈÛÌfi ÙÔ˘ ÎfiÏÔ˘ Î·È ÙÔ˘ ÚˆÎÙÔ‡ Ì GBS. ™ÙȘ ·ÔÈÎÈṲ̂Ó˜ Á˘Ó·›Î˜ ¯ÔÚËÁÂ›Ù·È ·ÓÙÈÌÈÎÚԂȷ΋ ·ÁˆÁ‹ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÙÔÎÂÙÔ‡. ŸÛÔÓ ·ÊÔÚ¿ ÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘, ·ÍÈÔÏÔÁ‹ıËÎ·Ó Ô ÚfiˆÚÔ˜ ÙÔÎÂÙfi˜ (‰È¿ÚÎÂÈ· ·ËÛ˘ <37 ‚‰ÔÌ¿‰Â˜), Ë Ú‹ÍË ÙˆÓ ÂÌ‚Ú˘˚ÎÒÓ ˘Ì¤ÓˆÓ >18 ÒÚ˜ Î·È Ë ˘ÚÂÙÈ΋ ΛÓËÛË Ù˘ ÂÈÙfiÎÔ˘ (≥38ÔC). ∞fi Ù· ÛÙÔȯ›· Ô˘ ‰ËÌÔÛȇıËÎ·Ó ·fi ÙȘ ‰‡Ô ÛÙÚ·ÙËÁÈΤ˜ ÚÔÛ¤ÁÁÈÛ˘, Ê·›ÓÂÙ·È fiÙÈ ÂÈÙ‡¯ıËΠÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ ÓÂÔÁÓÈ΋˜ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÛÈÌfiÙËÙ·˜ ·fi GBS, ¯ˆÚ›˜ ˆÛÙfiÛÔ Ó· ˘¿Ú¯ÂÈ ¿ÌÂÛË Û‡ÁÎÚÈÛË Û ÌÂÁ¿Ï˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ (36). ¶ÚfiÛÊ·ÙË ÎÏÈÓÈ΋ ÌÂϤÙË ÛÙȘ ∏¶∞ ¤‰ÂÈÍ fiÙÈ Ë ÔÏÈÙÈ΋ ·ÓÙÈÌÂÙÒÈÛ˘ Ì ‚¿ÛË ÙÔÓ ·ÔÈÎÈÛÌfi ‹Ù·Ó ηٿ 50% ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚË ·fi ÙËÓ ÔÏÈÙÈ΋ ÚÔÛ¤ÁÁÈÛ˘ Ì ‚¿ÛË ÙËÓ ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· ÎÈÓ‰‡ÓÔ˘ (37). ªÂ ‚¿ÛË Ù· Ó¤· ÛÙÔȯ›·, ÙÔ ∫¤ÓÙÚÔ ∂ϤÁ¯Ô˘ Î·È ¶ÚfiÏ˄˘ ÙˆÓ §ÔÈÌÒÍÂˆÓ ·Ó·ıÂÒÚËÛ ÙȘ Ô‰ËÁ›Â˜ ÙÔ˘ 1996 Î·È ·fi ÙÔÓ ∞‡ÁÔ˘ÛÙÔ ÙÔ˘ 2002 Û˘ÓÈÛÙ¿Ù·È Ô Î·ıÔÏÈÎfi˜ ¤ÏÂÁ¯Ô˜
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·19
19
¡ÂÔÁÓÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi µ-·ÈÌÔÏ˘ÙÈÎfi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ µ
fiÏˆÓ ÙˆÓ ÂÁ·ˆÓ ÁÈ· Ù˘¯fiÓ ·ÔÈÎÈÛÌfi ÙÔ˘˜ ·fi GBS Î·È ÌfiÓÔ ÛÙËÓ ÂÚ›ÙˆÛË fiÔ˘ Ù· ·ÔÙÂϤÛÌ·Ù· ‰ÂÓ Â›Ó·È ‰È·ı¤ÛÈÌ· ÚÔ ÙÔ˘ ÙÔÎÂÙÔ‡ Ï·Ì‚¿ÓÂÙ·È ˘fi„Ë Ô ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ (37). ªÂÙ¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙˆÓ Ó¤ˆÓ Ô‰ËÁÈÒÓ, ¤Ï·‚ ¯ÒÚ· ÌÈ· ÌÂϤÙË Ì ÛÎÔfi ÙËÓ ÂÍ·ÁˆÁ‹ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ Û¯ÂÙÈο Ì ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙˆÓ Ó¤ˆÓ Ô‰ËÁÈÒÓ, fiÛÔÓ ·ÊÔÚ¿ ÙË Ïԛ̈ÍË ·fi GBS. ™˘ÁÎÂÎÚÈ̤ӷ, ¤ÁÈÓ ۇÁÎÚÈÛË ÌÂٷ͇ Ù˘ ÂÚÈfi‰Ô˘ 2003-2005 (ÌÂÙ¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙˆÓ Ô‰ËÁÈÒÓ) Î·È Ù˘ ÂÚÈfi‰Ô˘ 2000-2001 (ÚÈÓ ÙËÓ ÂÊ·ÚÌÔÁ‹). ∏ Û˘¯ÓfiÙËÙ· Ù˘ ÚÒÈÌ˘ ÌÔÚÊ‹˜ Ù˘ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢ ‹Ù·Ó ηٿ 33% ¯·ÌËÏfiÙÂÚË Î·Ù¿ ÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô 2003-2005, Û ۯ¤ÛË Ì ÙËÓ ÂÚ›Ô‰Ô 2000-2001. ŸÛÔÓ ·ÊÔÚ¿ ÙË Û˘¯ÓfiÙËÙ· Ù˘ fi„ÈÌ˘ ÌÔÚÊ‹˜, ‰ÂÓ ˘‹Ú¯Â η̛· ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ (38). ∂ÓÒ Ë Û˘¯ÓfiÙËÙ· Ù˘ ÚÒÈÌ˘ ÌÔÚÊ‹˜ Ù˘ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢ Â›Ó·È ÙÔ˘Ï¿¯ÈÛÙÔÓ 20 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚË ·fi ÙË Û˘¯ÓfiÙËÙ· ÙÔ˘ ÓÂÔÁÓÈÎÔ‡ ¤ÚËÙ·, Ù˘ Û‡ÊÈÏ˘ Î·È Ù˘ ÂÚ˘ıÚ¿˜, ÂÓÙÔ‡ÙÔȘ ‰ÂÓ ˘¿Ú¯ÂÈ Ì¤¯ÚÈ Û‹ÌÂÚ· ÙÔ˘Ï¿¯ÈÛÙÔÓ Ô ·Ó¿ÏÔÁÔ˜ ÂÓıÔ˘ÛÈ·ÛÌfi˜ ÁÈ· ÚÔÁÂÓÓËÙÈο screening tests ÁÈ· Ïԛ̈ÍË ·fi GBS, fiˆ˜ Û˘Ì‚·›ÓÂÈ Ì ÙȘ ÚÔ·Ó·ÊÂÚfiÌÂÓ˜ ÏÔÈÌÒÍÂȘ. √ ηχÙÂÚÔ˜ ¯ÚfiÓÔ˜ ÁÈ· ¤ÏÂÁ¯Ô Ù˘ ÂÈÙfiÎÔ˘ Â›Ó·È Ë 28Ë Â‚‰ÔÌ¿‰· ·ËÛ˘ Î·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ¿ Ù˘ Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È Î·ÏÏȤÚÁÂȘ ·fi ÙÔÓ ÎfiÏÔ Î·È ÙÔÓ ÚˆÎÙfi. ™Â ÂÚ›ÙˆÛË Ô˘ Á›ÓÂÈ Ï‹„Ë Î·ÏÏȤÚÁÂÈ·˜ ÌfiÓÔ ÁÈ· Ì›· ·fi ÙȘ ‰‡Ô ÂÚÈÔ¯¤˜, ÙÔ ·ÔÙ¤ÏÂÛÌ· ÌÔÚ› Ó· Â›Ó·È „¢‰Ò˜ ·ÚÓËÙÈÎfi -fiÛÔÓ ·ÊÔÚ¿ ÙË ÊÔÚ›· Ù˘ ÂÈÙfiÎÔ˘- Û ÔÛÔÛÙfi ̤¯ÚÈ Î·È 25%. ŸÙ·Ó ˘¿Ú¯ÂÈ ·ÔÈÎÈÛÌfi˜ Ù˘ ÌËÙ¤Ú·˜, Û˘ÓÈÛÙ¿Ù·È Ë ¯ÔÚ‹ÁËÛË ¯ËÌÂÈÔÚÔʇϷ͢ ÙÔ˘Ï¿¯ÈÛÙÔÓ 4 ÒÚ˜ ÚÔ ÙÔ˘ ÙÔÎÂÙÔ‡, ÒÛÙ ӷ ÂÙ‡¯Ô˘Ì ÈηÓÔÔÈËÙÈο ıÂڷ¢ÙÈο ›‰·. øÛÙfiÛÔ, ÂÂȉ‹ ˘¿Ú¯ÂÈ Èı·ÓfiÙËÙ· ÙÔ ¤Ì‚Ú˘Ô Ó· ¤¯ÂÈ ÌÔÏ˘Óı› ÂÓ‰ÔÌ‹ÙÚÈ·, Ë Ì¤ıÔ‰Ô˜ ·˘Ù‹ ‰ÂÓ ÂÍ·ÛÊ·Ï›˙ÂÈ ¿ÓÙ· ηϋ ÚfiÁÓˆÛË (20). √È ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÓÔ¯ÔÔÈÔ‡ÓÙ·È ÁÈ· ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· ÂÚÈÁÂÓÓËÙÈ΋˜ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢ ›ӷÈ: Ô ÚfiˆÚÔ˜ ÙÔÎÂÙfi˜ (<37 ‚‰ÔÌ¿‰Â˜), Ë ÚfiˆÚË Ú‹ÍË ÙˆÓ ÂÌ‚Ú˘˚ÎÒÓ ˘Ì¤ÓˆÓ (<37 ‚‰ÔÌ¿‰Â˜), Ë ·Ú·ÙÂٷ̤ÓË Ú‹ÍË ÙˆÓ ÂÌ‚Ú˘˚ÎÒÓ ˘Ì¤ÓˆÓ (≥18 ÒÚ˜), Ô ˘ÚÂÙfi˜ Ù˘ ÌËÙ¤Ú·˜ (≥38,4ÔC Û ‰‡Ô ˘ÚÂÙÈο ·̷ٷ), ÙÔ ÈÛÙÔÚÈÎfi ÚÔËÁÔ‡ÌÂÓ˘ ·ËÛ˘ Ô˘ ›¯Â ÂÈϷΛ Ì Ïԛ̈ÍË ·fi GBS, Ë Ô˘ÚÔÏԛ̈ÍË Ù˘ ÌËÙ¤Ú·˜ ·fi GBS, Ë ¯ÔÚÈÔ·ÌÓÈÔÓ›Ùȉ· Î·È Ë Ôχ‰˘ÌË Î‡ËÛË (39,40).
∞ÓÙÈÌÂÙÒÈÛË ™Â οı ÚfiˆÚÔ ÓÂÔÁÓfi Ì ÛÔ‚·Ú‹ ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· Ë ÔÔ›· ÂΉËÏÒÓÂÙ·È ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË, Ô ·È‰›·ÙÚÔ˜ Â›Ó·È ˘Ô¯Úˆ̤ÓÔ˜ ÛÙË ‰È·-
ÊÔÚÈ΋ ‰È¿ÁÓˆÛË Ó· Û˘ÌÂÚÈÏ¿‚ÂÈ Î·È ÙË ÛÙÚÂÙÔÎÔÎÎÈ΋ Ïԛ̈ÍË. ∏ ÎÏÈÓÈ΋ Î·È Ë ·ÎÙÈÓÔÏÔÁÈ΋ ÂÈÎfiÓ· Ù˘ Ïԛ̈͢ ·fi GBS Â›Ó·È ·ÚfiÌÔÈ· Ì ÙÔ Û‡Ó‰ÚÔÌÔ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ Î·È ÂÔ̤ӈ˜ Ú¤ÂÈ Ó· ¯ÔÚËÁÂ›Ù·È ÂÌÂÈÚÈ΋ ·ÓÙÈÌÈÎÚԂȷ΋ ·ÁˆÁ‹ ̤¯ÚȘ fiÙÔ˘ Ó· ÁÓˆÛÙÔÔÈËıÔ‡Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ Î·ÏÏÈÂÚÁÂÈÒÓ (41). ŸÙ·Ó ˘¿Ú¯Ô˘Ó ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Î·È Ì¤¯ÚÈ Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ Î·ÏÏÈÂÚÁÂÈÒÓ ·›Ì·ÙÔ˜ Ó· Â›Ó·È ‰È·ı¤ÛÈÌ·, Ù· ÓÂÔÁÓ¿ ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È Ì ·ÓÙÈ‚ÈoÙÈ΋ ·ÁˆÁ‹. ∆· ÓÂÔÁÓ¿ ÙˆÓ ÔÔ›ˆÓ ÔÈ ÌËÙ¤Ú˜ ¤Ï·‚·Ó ¯ËÌÂÈÔÚÔʇϷÍË Ú¤ÂÈ Ó· ıÂڷ‡ÔÓÙ·È Û‡Ìʈӷ ÌÂ Û˘ÁÎÂÎÚÈ̤Ó˜ Û˘ÛÙ¿ÛÂȘ. ™Â Û˘Ìو̷ÙÈο ÓÂÔÁÓ¿ ¯ÔÚËÁÔ‡ÓÙ·È ·ÓÙÈ‚ÈÔÙÈο Â˘Ú¤Ô˜ Ê¿ÛÌ·ÙÔ˜ ̤¯ÚȘ fiÙÔ˘ ÁÓˆÛÙÔÔÈËıÔ‡Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ Î·ÏÏÈÂÚÁÂÈÒÓ. ∆· ·Û˘Ìو̷ÙÈο ÙÂÏÂÈfiÌËÓ· ÓÂÔÁÓ¿, ÙˆÓ ÔÔ›ˆÓ ÔÈ ÌËÙ¤Ú˜ ¤Ï·‚·Ó ÂÓÈÎÈÏÏ›ÓË ‹ ·ÌÈÎÈÏÏ›ÓË ÙÔ˘Ï¿¯ÈÛÙÔÓ 4 ÒÚ˜ ÚÔ ÙÔ˘ ÙÔÎÂÙÔ‡, ‰ÂÓ ¯ÚÂÈ¿˙ÔÓÙ·È ÂÚ·ÈÙ¤Úˆ ıÂڷ›·. ∆· ·Û˘Ìو̷ÙÈο ÚfiˆÚ· (¢∫ ≤34 ‚‰ÔÌ¿‰Â˜), ηıÒ˜ Î·È ÂΛӷ ·ÔÈÎÈÛÌ¤ÓˆÓ ÌËÙ¤ÚˆÓ, ıÂڷ‡ÔÓÙ·È ÂÌÂÈÚÈο ÙÔ˘Ï¿¯ÈÛÙÔÓ ÁÈ· 72 ÒÚ˜. ∞Ó ÔÈ Î·ÏÏȤÚÁÂȘ Â›Ó·È ÙÂÏÈÎÒ˜ ıÂÙÈΤ˜ ‹ Ù· ÓÂÔÁÓ¿ ÂÌÊ·Ó›˙Ô˘Ó ÎÏÈÓÈο ÛËÌ›·, Ë ıÂڷ›· Û˘Ó¯›˙ÂÙ·È. ™˘ÁÎÂÎÚÈ̤ӷ, ·Ó ˘¿Ú¯ÂÈ ÌfiÓÔ ÛË„·ÈÌ›· ¯ˆÚ›˜ ÌËÓÈÁÁ›Ùȉ·, Ë ıÂڷ›· Â›Ó·È ÂÓ‰ÔÊϤ‚È· ÂÓÈÎÈÏÏ›ÓË ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 10 ËÌÂÚÒÓ, ÂÓÒ ·Ó ˘¿Ú¯ÂÈ ÌËÓÈÁÁ›Ùȉ· Ë ıÂڷ›· Â›Ó·È 14 Ë̤Ú˜ ÂÓ‰ÔÊϤ‚È· ÂÓÈÎÈÏÏ›ÓË (42) (¶›Ó·Î·˜ 1). À¿Ú¯ÂÈ ¤ÓÙÔÓË ‰È¯ÔÁӈ̛· ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÚÈÁÂÓÓËÙÈ΋ ıÂڷ›· ÙˆÓ ÌËÙ¤ÚˆÓ Ô˘ Â›Ó·È ·ÔÈÎÈṲ̂Ó˜ Ì GBS. ∏ ÂÚÈÁÂÓÓËÙÈ΋ ¯ËÌÂÈÔÚÔʇϷÍË ÌÂÈÒÓÂÈ ÙË ÓÂÔÁÓÈ΋ Î·È ÌËÙÚÈ΋ ÓÔÛËÚfiÙËÙ· ÌfiÓÔ fiÙ·Ó ˘¿Ú¯Ô˘Ó ÌËÙÚÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘. øÛÙfiÛÔ, ˘¿Ú¯Ô˘Ó ÌÂϤÙ˜ ÔÈ Ôԛ˜ ˘ÔÛÙËÚ›˙Ô˘Ó fiÙÈ Ë ÂÚÈÁÂÓÓËÙÈ΋ ¯ËÌÂÈÔÚÔʇϷÍË ÌÂÈÒÓÂÈ ÛËÌ·ÓÙÈο ÙË Ïԛ̈ÍË ·fi GBS, ·ÎfiÌË Î·È Û ·Ô˘Û›· ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘ (43). µÂ‚·›ˆ˜, Ù· ıÂÙÈο ·ÔÙÂϤÛÌ·Ù· ·fi ÙËÓ ÂÎÏÂÎÙÈ΋ ¯ËÌÂÈÔÚÔʇϷÍË ı· Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È ˘fi„Ë Û ۇÁÎÚÈÛË Ì ÙËÓ Èı·ÓfiÙËÙ· ·ÏÏÂÚÁÈ΋˜ ·ÓÙ›‰Ú·Û˘ ‹ ·ÎfiÌË Î·È ÙËÓ ·Ó¿Ù˘ÍË ÂÓfi˜ ·ÓıÂÎÙÈÎÔ‡ ÏËı˘ÛÌÔ‡.
™˘ÌÂÚ¿ÛÌ·Ù· ∏ ‰È¿ÁÓˆÛË Î·È Ë ıÂڷ›· Ù˘ ÂÚÈÁÂÓÓËÙÈ΋˜ Ïԛ̈͢ ·fi GBS Û˘Ó¯›˙ÂÈ Ó· ·ÔÙÂÏ› ¤Ó· ÌÂÁ¿ÏÔ Úfi‚ÏËÌ·. ¡¤Â˜ ‰ÔÎÈ̷ۛ˜ ÁÈ· ÙËÓ ¤ÁηÈÚË ·Ó›¯Ó¢ÛË ÙÔ˘ ÛÙÚÂÙfiÎÔÎÎÔ˘ ÚÔÛ‰›‰Ô˘Ó ÂÏ›‰Â˜ ÁÈ· ηχÙÂÚË ÚfiÁÓˆÛË. øÛÙfiÛÔ, ‰ÂÓ ¤¯Ô˘Ó Á›ÓÂÈ ·ÎfiÌË Î·Ù·ÓÔËÙÔ› ÔÈ Ì˯·ÓÈÛÌÔ› Ì ÙÔ˘˜ ÔÔ›Ô˘˜ οÔÈÔÈ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ› ÚÔηÏÔ‡Ó Ïԛ̈ÍË, ÂÓÒ ¿ÏÏÔÈ ÚÔηÏÔ‡Ó ÌfiÓÔ ·Û˘Ìو̷ÙÈÎfi ·ÔÈÎÈÛÌfi. ¶·È‰È·ÙÚÈ΋ 2009;72:16-22
Pediatric Jan-Feb 09
16-03-09
14:56
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20
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∞ÓÙÈ‚›ˆÛË ÛÙË ÌËÙ¤Ú· ÁÈ· Èı·Ó‹ ¯ÔÚÈÔ·ÌÓÈÔÓ›Ùȉ·
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¶ÂÚÈÔÚÈṲ̂ÓË ·ÍÈÔÏfiÁËÛË5 ¶·Ú·Ù‹ÚËÛË ≥ 48 ÒÚ˜ ™Â ˘Ô„›· ÛË„·ÈÌ›·˜, Ï‹Ú˘ ‰È·ÁÓˆÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜2 Î·È ÂÌÂÈÚÈ΋ ıÂڷ›·3
≥ 4 ÒÚ˜ Ÿ¯È ·ÍÈÔÏfiÁËÛË Ÿ¯È ıÂڷ›· ¶·Ú·Ù‹ÚËÛË ≥48 ÒÚ˜6 1
∂¿Ó ‰ÂÓ ¤¯ÂÈ ÚÔËÁËı› ÚÔÊ˘Ï·ÎÙÈ΋ ·ÓÙÈ‚ÈÔÙÈ΋ ¯ÔÚ‹ÁËÛË ÛÙË ÌËÙ¤Ú·, ·Ú¿ ÙȘ ÂӉ›ÍÂȘ, ˘¿Ú¯Ô˘Ó ·Ó·Ú΋ ÛÙÔȯ›· ÁÈ· ÙË Û˘ÓÈÛÙÒÌÂÓË ·ÓÙÈÌÂÙÒÈÛË. 2 ¶ÂÚÈÏ·Ì‚¿ÓÂÈ ÁÂÓÈ΋ ·›Ì·ÙÔ˜, ηÏÏȤÚÁÂÈ· ·›Ì·ÙÔ˜ Î·È ·ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·ÎÔ˜ Â¿Ó ˘¿Ú¯ÂÈ ·Ó·Ó¢ÛÙÈ΋ ·Ó¿ÚÎÂÈ·. ∂¿Ó ˘¿Ú¯Ô˘Ó ÛËÌ›· ÛË„·ÈÌ›·˜, Û˘ÓÈÛÙ¿Ù·È Î·È ÔÛÊ˘ÔÓˆÙÈ·›· ·Ú·Î¤ÓÙËÛË. 3 ∏ ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ ÂÍ·ÚÙ¿Ù·È ·fi Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ηÏÏȤÚÁÂÈ·˜ ·›Ì·ÙÔ˜ Î·È Ù˘ ηÏÏȤÚÁÂÈ·˜ ∂¡À, ηıÒ˜ Î·È ·fi ÙËÓ ÎÏÈÓÈ΋ ÔÚ›· ÙÔ˘ ÓÂÔÁÓÔ‡. ∂¿Ó Ù· ·ÔÙÂϤÛÌ·Ù· ‰ÂÓ ‰Â›¯ÓÔ˘Ó ÌÈÎÚԂȷ΋ ÌfiÏ˘ÓÛË, Ë ıÂڷ›· ‰È·ÚΛ 48 ÒÚ˜. 4 ∞ÊÔÚ¿ ¯ÔÚ‹ÁËÛË ÂÓÈÎÈÏÏ›Ó˘, ·ÌÈÎÈÏÏ›Ó˘ ‹ ÎÂÊ·˙ÔÏ›Ó˘. 5 °ÂÓÈ΋ ·›Ì·ÙÔ˜ Î·È Î·ÏÏȤÚÁÂÈ· ·›Ì·ÙÔ˜. 6 ŒÓ· Ê·ÈÓÔÌÂÓÈο ˘ÁȤ˜ ÓÂÔÁÓfi, ÙÔ ÔÔ›Ô ÁÂÓÓ‹ıËΠ̠ËÏÈΛ· ·ËÛ˘ ≥36 ‚‰ÔÌ¿‰Â˜ Î·È ÙÔ˘ ÔÔ›Ô˘ Ë ÌËÙ¤Ú· ¤¯ÂÈ Ï¿‚ÂÈ ·ÓÙÈ‚ÈÔÙÈ΋ ·ÁˆÁ‹ ≥4 ÒÚ˜ ÚÔ ÙÔ˘ ÙÔÎÂÙÔ‡, ÌÔÚ› Ó· ¿ÚÂÈ ÂÍÈÙ‹ÚÈÔ ÌÂÙ¿ ·fi 24 ÒÚ˜ ·Ú·ÎÔÏÔ‡ıËÛ˘, Â¿Ó ÏËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ÁÈ· ÂÍÈÙ‹ÚÈÔ Î·È ˘¿Ú¯ÂÈ ¤Ó· ¿ÙÔÌÔ ÈηÓfi Ó· ·ÎÔÏÔ˘ı‹ÛÂÈ Ï‹Úˆ˜ ÙȘ Ô‰ËÁ›Â˜. ™Â ¿ÏÏË ÂÚ›ÙˆÛË, ı· Ú¤ÂÈ Ó· ·Ú·Ì›ÓÂÈ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 48 ÒÚ˜.
ÕÏψÛÙÂ, ÌfiÓÔ ÙÔ 1-2% ÙˆÓ ÓÂÔÁÓÒÓ Ù· ÔÔ›· ÁÂÓÓÈÔ‡ÓÙ·È ·fi ·ÔÈÎÈṲ̂Ó˜ ÌËÙ¤Ú˜ ÂΉËÏÒÓÔ˘Ó ÎÏÈÓÈο ÓfiÛÔ (44). ªÂÁ¿ÏË Û˘˙‹ÙËÛË Á›ÓÂÙ·È Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÔÚÈ˙fiÓÙÈ· ÌÂÙ¿‰ÔÛË Ù˘ ÓfiÛÔ˘, ÛÙËÓ ÔÔ›· ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ·›˙ÂÈ Î·È Ë ¯ˆÚÔÙ·ÍÈ΋ ÔÚÁ¿ÓˆÛË ÙˆÓ ÓÂÔÁÓÔÏÔÁÈÎÒÓ ÙÌËÌ¿ÙˆÓ. ŸÙ·Ó ÓÂÔÁÓ¿ ·ÔÈÎÈṲ̂ӷ ÙÔÔıÂÙ‹ıËÎ·Ó ÎÔÓÙ¿ Û ÌË ·ÔÈÎÈṲ̂ӷ, ·Ú·ÙËÚ‹ıËΠfiÙÈ ÙÔ ÔÛÔÛÙfi ÌÂÙ¿‰ÔÛ˘ ·fi ÓÂÔÁÓfi Û ÓÂÔÁÓfi ‹Ù·Ó ·ÚÎÂÙ¿ ˘„ËÏfi. ∏ ˘„ËÏ‹ ˘ÎÓfiÙËÙ· ÓÂÔÁÓÈÎÔ‡ ÏËı˘ÛÌÔ‡, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ۯÂÙÈο Ï›ÁÔ ÓÔÛËÏ¢ÙÈÎfi ÚÔÛˆÈÎfi, ¢ÓÔ› ÙË ÌÂÙ¿‰ÔÛË Ù˘ ÓfiÛÔ˘ (45). ∂Âȉ‹ Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÏÔÈÌÒÍÂˆÓ ·fi GBS ÛÙȘ ¤ÁÎ˘Â˜ Î·È ÛÙ· ÓÂÔÁÓ¿ ·ÊÔÚ¿ Û˘ÁÎÂÎÚÈ̤ÓÔ˘˜ ÔÚfiÙ˘Ô˘˜, Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· ·fi ÙÔ˘˜ ÂÚ¢ÓËÙ¤˜ ÁÈ· ÙË ‰ËÌÈÔ˘ÚÁ›· ÂÓfi˜ ηÈÓÔ‡ÚÁÈÔ˘ ÂÌ‚ÔÏ›Ô˘. ∏ ›Ù¢ÍË ·˘ÙÔ‡ ÙÔ˘ ÛÙfi¯Ô˘ ı· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó¿Ù˘ÍË Ó¤ˆÓ Paediatriki 2009;72:16-22
ÛÙÚ·ÙËÁÈÎÒÓ Ô˘ ı· ÚÔÛʤÚÔ˘Ó ÌÂÁ·Ï‡ÙÂÚË ÚÔÛÙ·Û›· ·fi ÙËÓ ÚÒÈÌË Î·È ÙËÓ fi„ÈÌË ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘. ∂ȉÈÎfiÙÂÚ·, Ô ÂÌ‚ÔÏÈ·ÛÌfi˜ ÌÔÚ› Ó· ‚ÔËı‹ÛÂÈ ÛÙËÓ ÚfiÏË„Ë Î¿ÔÈˆÓ ·ÓÂÈı‡ÌËÙˆÓ Î·Ù·ÛÙ¿ÛÂˆÓ ÔÈ Ôԛ˜ Û¯ÂÙ›˙ÔÓÙ·È Ì Ïԛ̈ÍË ·fi GBS, fiˆ˜ Ô ÚfiˆÚÔ˜ ÙÔÎÂÙfi˜ Î·È Ë ·Ô‚ÔÏ‹ (46-50). ∏ ÛË„·ÈÌ›· ‹ Î·È Ë ÌËÓÈÁÁ›Ùȉ· ·fi GBS Â›Ó·È ÌÈ· Ôχ ÛÔ‚·Ú‹ ÏÔÈÌ҉˘ ηٿÛÙ·ÛË ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·. ∏ Û˘¯ÓfiÙËÙ· Ù˘ ÓÂÔÁÓÈ΋˜ ÛÙÚÂÙÔÎÔÎÎÈ΋˜ Ïԛ̈͢ ÔÈΛÏÏÂÈ ·fi 0,5-3 ÂÚÈÙÒÛÂȘ ·Ó¿ ¯›ÏȘ ÁÂÓÓ‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ (51). øÛÙfiÛÔ, ˘¿Ú¯ÂÈ Û·Ê‹˜ Ù¿ÛË ÁÈ· Ì›ˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ Ù˘ ÚÒÈÌ˘ ÌÔÚÊ‹˜ ÌÂÙ¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙˆÓ ÂÚÈÁÂÓÓËÙÈÎÒÓ ÚÔÏËÙÈÎÒÓ Ì¤ÙÚˆÓ (52). ¶ÚÔ·ÙÂÈ, Û˘ÓÂÒ˜, fiÙÈ Ë ·Ó·ÁÓÒÚÈÛË ÙˆÓ ÌËÙÚÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡ÓÔ˘ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÁ΢ÌÔÛ‡Ó˘ (Ïԛ̈ÍË Ô˘ÚÔÔÈËÙÈÎÔ‡ ·fi GBS, ÚÔËÁÔ‡ÌÂÓÔ ÓÂÔÁÓfi Ì Ïԛ̈ÍË ·fi GBS, ¯ÔÚÈÔ·ÌÓÈÔÓ›Ùȉ· ‹ ˘ÚÂÙfi˜ ÂÚÈÁÂÓÓËÙÈο, ·Ú·ÙÂٷ̤ÓË
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¡ÂÔÁÓÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi µ-·ÈÌÔÏ˘ÙÈÎfi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ µ
Ú‹ÍË ÂÌ‚Ú˘˚ÎÒÓ ˘Ì¤ÓˆÓ >18 ÒÚ˜, ÚÔˆÚfiÙËÙ· Î·È ÊÔÚ›· ÙÔ˘ GBS) ‰È·‰Ú·Ì·Ù›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÚfiÏË„Ë Ù˘ ·Ó¿Ù˘Í˘ ÚÒÈÌ˘ ÌÔÚÊ‹˜ Ïԛ̈͢ ·fi GBS Û ÓÂÔÁÓ¿ (53). ∆¤ÏÔ˜, ÛËÌ·ÓÙÈÎfi ÚfiÏÔ Î·Ù¤¯ÂÈ Î·È Ë ÂÚÈÁÂÓÓËÙÈ΋ ·ÛÊ˘Í›·, fiˆ˜ ÚÔ·ÙÂÈ ·fi ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ (54-57). øÛÙfiÛÔ, Â›Ó·È ··Ú·›ÙËÙÔ Ó· ·ÍÈÔÏÔÁËıÔ‡Ó Î·È Ó· ÚÔÛ‰ÈÔÚÈÛÙÔ‡Ó Èı·ÓÔ› Ó¤ÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙË ÓÂÔÁÓÈ΋ ÓfiÛÔ ·fi GBS (40).
BÈ‚ÏÈÔÁÚ·Ê›· 1. Brown JH. Cultural differentiation of beta-hemolytic Streptococci of human and bovine sources. J Exp Med 1920;31:35-45. 2. Fry RM. Fatal infections caused by hemolytic Streptococcus group B. Lancet 1938;1:199-201. 3. Baker CJ, Edwards MS. Group B streptococcal infections. In: Remington JS, Klein JO. Infectious diseases of the fetus and newborn infant. 3rd ed. Philadelphia: Saunders; 1990. p. 742-810. 4. Boyer KM, Gadzala CA, Burd LI, Fisher DE, Paton JB, Gotoff SP. Selective intrapartum chemo prophylaxis of neonatal group B streptococcal early-onset disease. Epidemiologic rationale. J Infect Dis 1983;148:795-801. 5. Hamada S, Vearncombe M, McGeer A, Shah PS. Neonatal group B streptococcal disease: incidence, presentation, and mortality. J Matern Fetal Neonatal Med 2008;21:53-57. 6. Berardi A, Lugli L, Baronciani D, Creti R, Rossi K, Ciccia M et al. Group B streptococcal infections in a northern region of Italy. Pediatrics 2007;120:487-493. 7. Barcaite E, Bartusevicius A, Tameliene R, Kliucinskas M, Maleckiene L, Nadisauskiene R. Prevalence of maternal group B streptococcal colonisation in European countries. Acta Obstet Gynecol Scand 2008;87:260-271. 8. Larsen JW, Sever JL. Group B Streptococcus and pregnancy: a review. Am J Obstet Gynecol 2008;198:440-448. 9. Yagupsky P, Menegus MA, Powell KR. The changing spectrum of group B Streptococcal disease in infants: an eleven-year experience in a tertiary care hospital. Pediatr Infect Dis 1991;10:801-808. 10. Felgin RD, Adcock LM, Miller DJ. The immune system. In: Fanaroff AA, Martin RJ. Neonatal-perinatal medicine: diseases of the fetus and infant. 5th ed. St. Luis: Mosby year Book; 1992. p. 631. 11. Baker CJ, Kasper DL, Tager IR, Paredes A, Alpert S, McCormack WM, et al. Quantitative determination of antibody to capsular polysaccharide in infection with type III strains of group B streptococcus. J Clin Invest 1977;59: 810-818. 12. Centers for disease Control and Prevention. Prevention of perinatal group B streptococcal disease: a public health perspective. CDC. MMWR Morb Mortal Wkly Rep 1996; 45:1-24. 13. Kadanali A, Altoparlak U, Kadanali S. Maternal carriage and neonatal colonisation of group B streptococcus in eastern Turkey: prevalence, risk factors and antimicrobial resistance. Int J Clin Pract 2005;59:437-440. 14. Hakansson S, Axemo P, Bremme K, Bryngelsson AL, Wallin MC, Ekström CM, et al. Swedish Working Group For The Prevention of Perinatal Group B Streptococcal o
Infections. Group B streptococcal carriage in Sweden: a national study on risk factors for mother and infant colonisation. Acta Obstet Gynecol Scand 2008;87:50-58. 15. Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics 2005;115:1240-1246. 16. Hickman ME, Rench MA, Ferrieri P, Baker CJ. Changing epidemiology of group B streptococcal colonization. Pediatrics 1999;104:203-209. 17. Persson K, Christensen KK, Christensen P, Forsgren A, Jorgensen C, Persson PH. A symptomatic bacteriuria during pregnancy with special reference to group B streptococci. Scand J Infect Dis 1985;17:195-199. 18. Yancey MK, Duff P, Clark P, Kurtzer T, Frentzen BH, Kubilis P. Peripartum infection associated with vaginal group B streptococcal colonization. Obstet Gynecol 1994; 84:816-819. 19. Rubens CE, Wessels MR, Heggen LM, Kasper DL. Transposon mutagenesis of type III group B streptococcus: correlation of capsule expression with virulence. Proc Natl Acad Sci USA 1987;84:7208-7212. 20. Garland SM. Early-onset neonatal group B streptococcus (GBS) infection: associated obstetric risk factors. Aust NZ J Obstet Gynecol 1991;31:117-118. 21. Tsolia M, Psoma M, Gavrili S, Petrochilou V, Michalas S, Legakis N, et al. Group B streptococcus colonization of Greek pregnant women and neonates: prevalence, risk factors and serotypes. Clin Microbiol Infect 2003;9:832-838. 22. Centers for Disease Control and Prevention. Decreasing incidence of perinatal group B streptococcal disease-USA, 1993-1995. MMWR 1997;46:473-477. 23. Easmon CS, Hastings MJ, Clare AJ, Bloxham B, Marwood R, Rivers RP, et al. Nosocomial transmission of group B streptococci. Br Med J 1981;283:459-461. 24. Platt JS, O’Brien WF. Group B Streptococcus: prevention of early onset neonatal sepsis. Obstet Gynecol Surv 2003; 58:191-196. 25. Turow J, Spitzer AR. Group B streptococcal infection early onset disease, controversies in prevention guidelines and management strategies for the neonate. Clin Pediatr 2000;39:317-326. 26. Schrag SJ, Zywicki S, Farley MM, Reingold AL, Harrison LH, Lefkowitz LB, et al. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000;342:15-20. 27. Clark P, Armer T, Duff P, Davidson K. Assessment of a rapid latex agglutination test for group B streptococcal colonization of the genital tract. Obstet Gynecol 1992;79: 358-363. 28. Aziz N, Baron EJ, D’Souza H, Nourbakhsh M, Druzin ML, Benitz WE. Comparison of rapid intrapartum screening methods for group B streptococcal vaginal colonization. J Matern Fetal Neonatal Med 2005;18:225-229. 29. Samadi R, Stek A, Greenspoon JS. Evaluation of a rapid optical immunoassay-based test for group B streptococcus colonization in intrapartum patients. J Matern Fetal Med 2001;10:203-208. 30. Atkins KL, Atkinson RM, Shanks A, Parvin CA, Dunne WM, Gross G. Evaluation of polymerase chain reaction for group B streptococcus detection using an improved culture method. Obstet Gynecol 2006;108:488-491. 31. Chan KL, Levi K, Towner KJ, Weston VC, Ramsay MM, ¶·È‰È·ÙÚÈ΋ 2009;72:16-22
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Kean LH. Evaluation of the sensitivity of a rapid polymerase chain reaction for detection of group B streptococcus. J Obstet Gynecol 2006;26:402-406. 32. Bergseng H, Bevanger L, Rygg M, Bergh K. Real-time PCR targeting the sip gene for detection of group B Streptococcus colonization in pregnant women at delivery. J Med Microbiol 2007;56:223-228. 33. ACOG Committee Opinion. Prevention of early onset group B streptococcal disease in newborns. No 173 - June 1996. Committee on Obstetric Practice, American College of Obstetrics and Gynecologists. Int J Gynecol Obstet 1996;54:205. 34. American Academy of Pediatrics. Revised guidelines for prevention of early onset group B streptococcal (GBS) infection. American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics 1997;99:489-496. 35. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Morb Mortal Wkly Rep 2002;51:1-22. 36. Lin FY, Brenner RA, Johnson YR, Azimi PH, Philips JB, Regan JA, et al. The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early onset neonatal group B streptococcal disease. Am J Obstet Gynecol 2001;184:1204-1210. 37. Schrag SJ, Zell ER, Lynfield R, Roome A, Arnold KE, Craig AS, et al. A population based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med 2002;347:233-239. 38. Centers for Disease Control and Prevention (CDC). Perinatal group B streptococcal disease after universal screening recommendations - United States, 2003-2005. MMWR 2007;56:701-705. 39. American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Guidelines for prevention of group B streptococcal (GBS) infection by chemoprophylaxis. Pediatrics 1992;90:775-778. 40. Oddie S, Embleton ND. Risk factors for early-onset neonatal group B streptococcal sepsis: case control study. Br Med J 2002;325:308-312. 41. Gibbs RS, Schrag S, Schuchat A. Perinatal infections due to group B streptococci. Obstet Cynecol 2004;104:1062-1076. 42. Edwards MS, Baker CJ. Group B streptococcal infections. In: Remington JS, Klein JO, editors. Infections diseases of the fetus and newborn infant. 5th ed. Philadelphia: Saunder; 2001. p. 1091-1156.
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43. Garland SM, Fliegner JR. Group B streptococcus (GBS) and neonatal infections: the case for intrapartum chemoprophylaxis. Aust & NZ J Obstet Gynaecol 1991;31: 119-122. 44. Rener RM, Rener A, Schmid S, Hoesli I, Nars P, Holzgreve W, et al. Efficacy of a strategy to prevent neonatal earlyonset group B streptococcal (GBS) sepsis. J Perinat Med 2006;34:32-38. 45. Platt MV, Gilson GJ. Group B streptococcal disease in the perinatal period. Am Fam Physician 1994;49:434-442. 46. Johri AK, Paoletti LC, Glaser P, Dua M, Sharma PK, Grandi G, et al. Group B Streptococcus: global incidence and vaccine development. Nat Rev Microbiol 2006;4:932-942. 47. Patten S, Vollman AR, Manning SD, Mucenski M, Vidakovich J, Davies HD. Vaccination for Group B Streptococcus during pregnancy: attitudes and concerns of women and health care providers. Soc Sci Med 2006;63: 347-358. 48. Paoletti LC, Kasper DL. Glycoconjugate vaccines to prevent group B streptococcal infections. Expert Opin Biol Ther 2003;3:975-984. 49. Baker CJ, Rench MA, McInnes P. Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine. Vaccine 2003;21:3468-3472. 50. Paoletti LC, Madoff LC. Vaccines to prevent neonatal GBS infection. Semin Neonatol 2002;7:315-323. 51. Schuchat A. Group B streptococcus. Lancet 1999;353:51-56. 52. Schrag SJ, Zywicki S, Farley MM, Reingold AL, Harrison LH, Lefkowitz LB, et al. Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 2000;342:15-20. 53. Smaill F. Intrapartum antibiotics for group B streptococcal colonization. Cochrane database Syst Rev 2000;2:CD000115. 54. Presta G, Rosati E, Giannuzzi R, Del Vecchio A, Lozupone A, Criscuolo M, et al. Prolonged fetal bradycardia as the presenting clinical sign in Streptococcus agalactiae chorioamnionitis. J Perinat Med 2004;32:535-537. 55. Peevy KJ, Chalhub EG. Occult group B streptococcal infection: an important cause of intrauterine asphyxia Am J Obstet Gynecol 1983;146:989-990. 56. Jones S, Athan E, Viggers J. Prevention of recurrent fetal death in utero due to group B streptococcal chorioamnionitis. Aust N Z J Obstet Gynaecol 2004;44:356-357. 57. Ledger WJ. Perinatal infections and fetal/neonatal brain injury. Curr Opin Obstet Gynecol 2008;20:120-124.
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¶ÔÏ˘Û·Î¯·ÚȉÈο ·ÓÙÈÁfiÓ· – Û˘˙¢Á̤ӷ ÂÌ‚fiÏÈ·: ·ÓÔÛȷ΋ ÌÓ‹ÌË Î·È ·Ó·ÌÓËÛÙÈΤ˜ ‰fiÛÂȘ π.£. ∫·‚·ÏÈÒÙ˘ ¶ÂÚ›ÏË„Ë: ™˘˙ËÙÔ‡ÓÙ·È Ù· ÚÔ‚Ï‹Ì·Ù· ÙˆÓ ÔÏ˘Û·Î¯·ÚȉÈÎÒÓ ·ÓÙÈÁfiÓˆÓ, ÙÔÓ›˙ÔÓÙ·È Ù· ÌÂÈÔÓÂÎÙ‹Ì·Ù¿ ÙÔ˘˜, ·Ó·Ï‡ÂÙ·È Ë ·ÓÔÛȷ΋ ·¿ÓÙËÛË ÛÙ· ·ÓÙÈÁfiÓ· ·˘Ù¿ Î·È ·Ó·Ê¤ÚÔÓÙ·È Ù· ÏÂÔÓÂÎÙ‹Ì·Ù· ÙˆÓ Û˘˙¢ÁÌ¤ÓˆÓ ·ÓÙÈÁfiÓˆÓ-ÂÌ‚ÔÏ›ˆÓ. ªÂ ‚¿ÛË Ù· ·Ú·¿Óˆ, Á›ÓÔÓÙ·È ÛΤ„ÂȘ ÁÈ· ÚÔÛı‹ÎË ·Ó·ÌÓËÛÙÈÎÒÓ ‰fiÛÂˆÓ ÛÙ· Û˘ÁÎÂÎÚÈ̤ӷ ÂÌ‚fiÏÈ·. §¤ÍÂȘ ÎÏÂȉȿ: ∂Ì‚fiÏÈ·, ·ÓÔÛ›·, ·È‰È¿.
¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ∂ȉÈÎÒÓ ¶·ı‹ÛÂˆÓ £ÂÛÛ·ÏÔӛ΢ AÏÏËÏÔÁÚ·Ê›·: π. ∫·‚·ÏÈÒÙ˘ kavagrc@gmail.com ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¡ÔÛÔÎÔÌÂ›Ô ∂ȉÈÎÒÓ ¶·ı‹ÛÂˆÓ °Ú. §·ÌÚ¿ÎË 13 54638 £ÂÛÛ·ÏÔÓ›ÎË
Polysaccharide antigens – conjugated vaccines: immune memory and anamnestic doses π. Kavaliotis Abstract: This is an analysis of the immune response to polysaccharide antigens and conjugated vaccines. Based on this analysis, there is a rationale for adding more anamnestic doses for conjugated vaccines. Key words: Vaccines, immunity, children.
∆· Û˘˙¢Á̤ӷ ÔÏ˘Û·Î¯·ÚȉÈο ÂÌ‚fiÏÈ· ›¯·Ó Ì›˙ÔÓ˜ ÂÈÙÒÛÂȘ ÛÙȘ ·ÓÙ›ÛÙÔȯ˜ ‰ÈÂÈÛ‰˘ÙÈΤ˜ ÏÔÈÌÒÍÂȘ ÙˆÓ ·È‰ÈÒÓ fiÙ·Ó ÂÈÛ‹¯ıËÛ·Ó ÛÙ· ÂıÓÈο ÚÔÁÚ¿ÌÌ·Ù· ÂÌ‚ÔÏÈ·ÛÌÒÓ. ∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ·˘Ù‹ ›¯Â Û¯¤ÛË Ì ÚÔÛÙ·Û›· ̤ۈ ·Ú·ÁˆÁ‹˜ ·ÓÙÈۈ̿وÓ, ηıÒ˜ Î·È Ì¤Ûˆ Ù˘ ÚÔηÏÔ‡ÌÂÓ˘ ¤ÌÌÂÛ˘ ·ÓÔÛ›·˜. ™ËÌ·ÓÙÈÎfi ÏÂÔÓ¤ÎÙËÌ· ÙˆÓ ÂÌ‚ÔÏ›ˆÓ ·˘ÙÒÓ ‹Ù·Ó Î·È Â›Ó·È Ë ÈηÓfiÙËÙ· ·ÓÔÛȷ΋˜ ‰È¤ÁÂÚÛ˘ (ÚˆÙÔÁÂÓ‹˜ ·¿ÓÙËÛË, priming) ·fi ÙË ‚ÚÂÊÈ΋ ËÏÈΛ· (1-4). ∂›Ó·È ÁÓˆÛÙfi fiÙÈ ÙÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ· ·ÔÙÂÏÂ›Ù·È ·fi ‰‡Ô ·ÏÏËÏÔ-ÂÈÎ·Ï˘ÙfiÌÂÓ· ÙÌ‹Ì·Ù·, ÙÔ ÏÂÌÊÈÎfi Î·È ÙÔ ‰ÈÎÙ˘ÔÂÓ‰ÔıËÏÈ·Îfi Û‡ÛÙËÌ·. ∆· ÙÌ‹Ì·Ù· ·˘Ù¿ ÊÈÏÔÍÂÓÔ‡Ó Ù· ·ÚÈ· ·ÓÔÛȷο ·ÙÙ·Ú·, Ô˘ Â›Ó·È Ù· Ï¢ÎÔ·ÙÙ·Ú·: Ô˘‰ÂÙÂÚfiÊÈÏ·, ˈÛÈÓfiÊÈÏ·, ‚·ÛÂfiÊÈÏ·, ÌÔÓÔ·ÙÙ·Ú·, Ì·ÎÚÔÊ¿Á·, ·ÙÙ·Ú· ÊÔÓ›˜, T-ÏÂÌÊÔ·ÙÙ·Ú·, B-ÏÂÌÊÔ·ÙÙ·Ú·. ∆· ·ÙÙ·Ú· ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÂÈÎÔÈÓˆÓÔ‡Ó ÌÂٷ͇ ÙÔ˘˜ ̤ۈ ÌÔÚ›ˆÓ Ô˘ ηÏÔ‡ÓÙ·È Î˘ÙÙ·ÚÔΛÓ˜. H ·¿ÓÙËÛË ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÚÔ˜ Ù· ·ıÔÁfiÓ·-ÂÈÛ‚ÔÏ›˜ Â›Ó·È ‰ÈÙÙ‹: ÌË ÂȉÈ΋/¤ÌÊ˘ÙË (innate) Î·È ÂȉÈ΋ ›ÎÙËÙË (adaptive). ∏ ÌË ÂȉÈ΋ Â›Ó·È Ù·¯Â›· Î·È ¿ÌÂÛË, ÛÙÂÚÂ›Ù·È ·ÓÔÛȷ΋˜ ÌÓ‹Ì˘ Î·È Û˘Ì‚·›ÓÂÈ ÛÙËÓ ›‰È· ¤ÎÙ·ÛË, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ fiÛÔ Û˘¯Ó¿ ÙÔ ·ıÔÁfiÓÔ Û˘Ó·ÓÙ¿ ÙÔÓ ÍÂÓÈÛÙ‹. ∞·ÓÙ¿ ·ÎfiÌË Î·È ÛÙ· ·ÏÔ‡ÛÙÂÚ· ›‰Ë ÙÔ˘ ˙ˆÈÎÔ‡ ‚·ÛÈÏ›Ԣ.
Department of Paediatrics, Infectious Diseases Hospital, Thessaloniki, Greece Correspondence: π. Kavaliotis kavagrc@gmail.com Department of Paediatrics Infectious Diseases Hospital 13, Gr. Lampraki St. 54638 Thessaloniki Greece
∏ ÂȉÈ΋ ·¿ÓÙËÛË Â›Ó·È ‚Ú·‰‡ÙÂÚË, ¤¯ÂÈ ÌÓ‹ÌË Î·È ÂÓÈÛ¯‡ÂÙ·È Û ·ÓÂÈÏËÌ̤Ó˜ ÂÎı¤ÛÂȘ ÙÔ˘ ÍÂÓÈÛÙ‹ ÛÙÔ ›‰ÈÔ ·ıÔÁfiÓÔ. ∞ÔÙÂÏ› ÙËÓ Ô˘Û›· ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜. ∫·È ÔÈ ‰‡Ô ·ÓÔÛȷΤ˜ ··ÓÙ‹ÛÂȘ ÂÈÙ˘Á¯¿ÓÔÓÙ·È Ì ÙË ÌÂٷ͇ ÙÔ˘˜ Û˘ÓÂÚÁ·Û›· Î·È ÙÔÓ Û˘ÓÙÔÓÈÛÌfi, ÒÛÙ ӷ ÂÚÈÔÚ›ÛÔ˘Ó ÙÔÓ ÂÈÛ‚ÔϤ· (5-8). ∏ ÌË ÂȉÈ΋ ·ÓÔÛȷ΋ ·¿ÓÙËÛË Â›Ó·È ÌÂÓ Ù·¯Â›· Î·È ¿ÌÂÛË, ‰ÂÓ ÌÔÚ› fï˜ Ó· ÙÚÔÔÔÈËı› Î·È ÛÙÂÚÂ›Ù·È ÂȉÈÎfiÙËÙ·˜. ∏ ÂȉÈ΋ ›ÎÙËÙË ·ÓÔÛ›· Â›Ó·È ÂÍÂȉÈÎÂ˘Ì¤ÓË, ÌÔÚ› Ó· ‰ÈÂÁÂÚı› ÒÛÙ ӷ ‰ÒÛÂÈ ÛÙË Û˘Ó¤¯ÂÈ· ÌÈ· Ù·¯Â›· Î·È ÚÔÛٷ٢ÙÈ΋ ·ÓÙÈۈ̷ÙÈ΋ ·¿ÓÙËÛË Û ·ÎfiÏÔ˘ıË ¤ÎıÂÛË ÛÙÔ ›‰ÈÔ ·ıÔÁfiÓÔ (ÂÓÂÚÁËÙÈ΋ ·ÓÔÛ›·), ·ÏÏ¿ ‰ÂÓ Â›Ó·È ¿ÌÂÛË Î·È ··ÈÙ› ·ÚÎÂÙ¤˜ Ë̤Ú˜ ÁÈ· Ó· ·Ó·Ù˘¯ı› (5,7,8,9). ™ÎÔfi˜ ÙˆÓ ÂÌ‚ÔÏÈ·ÛÌÒÓ Â›Ó·È ·ÎÚÈ‚Ò˜ ·˘Ù‹ Ë ‰È¤ÁÂÚÛË Ù˘ ·ÓÔÛ›·˜ Ì ÙËÓ ·ÍÈÔÔ›ËÛË ÙˆÓ ·ÓÙÈÁÔÓÈÎÒÓ È‰ÈÔÙ‹ÙˆÓ ÙÔ˘ ·ıÔÁfiÓÔ˘, ¯ˆÚ›˜ ÙÔ ¿ÙÔÌÔ Ó· ¤¯ÂÈ ¤ÏıÂÈ ÚÔËÁÔ˘Ì¤Óˆ˜ Û ·ʋ Ì ÙÔ ·ıÔÁfiÓÔ. ∏ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ·ÓÔÛÔÔ›ËÛË Ô˘ Ô‰ËÁ› Û ̷ÎÚÔ¯ÚfiÓÈ· ÚÔÛÙ·Û›· ··ÈÙ› ÙËÓ ·Ú·ÁˆÁ‹ ÌÓËÌÔÓÈÎÒÓ µ ΢ÙÙ¿ÚˆÓ. ∞˘Ùfi ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙȘ ·Ú¯ÈΤ˜ Î·È ÂfiÌÂÓ˜ ‰fiÛÂȘ ÂÌ‚ÔÏ›ˆÓ Ô˘ Û˘Á¯ÚfiÓˆ˜ ‚ÔËıÔ‡Ó Û ·˘ÍË̤ÓË Û˘Ó¿ÊÂÈ·-Û˘ÁÁ¤ÓÂÈ· (affinity-avidity) ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÚÔ˜ ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÓÙÈÁfiÓÔ. øÛÙfiÛÔ, Ù· Ú¿ÁÌ·Ù· Ê·›ÓÂÙ·È fiÙÈ ‰ÂÓ Â›Ó·È ÙfiÛÔ ·Ï¿ Î·È ÔÈ ÁÓÒÛÂȘ ¶·È‰È·ÙÚÈ΋ 2009;72:23-28
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∂ÈÎfiÓ· 5 ∂ÈÎfiÓ˜ 1-5. ∞ÓÔÛȷ΋ ·¿ÓÙËÛË - ·fi ÙË ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ú·ÔÌ‹ ·Ú. 2. Paediatriki 2009;72:23-28
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¶ÔÏ˘Û·Î¯·ÚȉÈο ·ÓÙÈÁfiÓ· – Û˘˙¢Á̤ӷ ÂÌ‚fiÏÈ·
Ì·˜ ÁÈ· ÙËÓ ·ÓÔÛȷ΋ ÌÓ‹ÌË Û ÌÔÚÈ·Îfi Â›Â‰Ô Â›Ó·È ·ÙÂÏ›˜ (2,3,8,9). ¶ÚÈÓ ÙËÓ ¤ÎıÂÛË Û οÔÈÔ ·ÓÙÈÁfiÓÔ ‰ÂÓ ˘¿Ú¯Ô˘Ó ÌÓËÌÔÓÈο µ ·ÙÙ·Ú· ÁÈ· ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÓÙÈÁfiÓÔ, Ô‡Ù ·˘ÙfiÌ·ÙË ¤ÎÎÚÈÛË ·ÓÙÈÛˆÌ¿ÙˆÓ ÂȉÈÎÒÓ ÁÈ· ÙÔ ·ÓÙÈÁfiÓÔ (5,7). ∆· ÂÚÈÛÛfiÙÂÚ· ·ÓÙÈÁfiÓ· ··ÈÙÔ‡Ó ÙËÓ ·ÏÏËÏ›‰Ú·ÛË µ Î·È T ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ÁÈ· Ó· ÚÔηϤÛÔ˘Ó ·ÓÔÛȷ΋ ·¿ÓÙËÛË (ı˘ÌÔÂÍ·ÚÙÒÌÂÓ· ·ÓÙÈÁfiÓ·, T-thymus-dependent antigens). ªÂÚÈο, fï˜, ·ÓÙÈÁfiÓ· ÂÎÏ‡Ô˘Ó ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ µ ΢ÙÙ¿ÚˆÓ Î·È ÙËÓ ·Ú·ÁˆÁ‹ ·ÓÙÈÛˆÌ¿ÙˆÓ ¯ˆÚ›˜ ÙË ‚Ô‹ıÂÈ· ÙˆÓ ∆ ΢ÙÙ¿ÚˆÓ (ı˘ÌÔ·ÓÂÍ¿ÚÙËÙ· ·ÓÙÈÁfiÓ·, T-independent antigens). ∆· ·ÓÙÈÁfiÓ· ·˘Ù¿ ‰ÂÓ Â›Ó·È Èηӿ ·ÓÔÛÔÁfiÓ· Û ·È‰È¿ ÌÈÎÚfiÙÂÚ· ÙˆÓ 2 ¯ÚfiÓˆÓ (3,10,11). ™ÙËÓ Î·ÙËÁÔÚ›· ·˘Ù‹ ·Ó‹ÎÔ˘Ó Ù· ÔÏ˘Û·Î¯·ÚȉÈο ·ÓÙÈÁfiÓ·. ∏ Û‡˙¢ÍË Ù¤ÙÔÈˆÓ ·ÓÙÈÁfiÓˆÓ Ì ڈÙ½ÓË-ÊÔÚ¤· Â›Ó·È ÈηӋ Ó· «ÌÂÙ·‚¿ÏÂÈ» ÙȘ ȉÈfiÙËÙ¤˜ ÙÔ˘˜ Î·È Ó· ‰ÈÂÁ›ÚÂÈ ı˘ÌÔÂÍ·ÚÙÒÌÂÓË ·ÓÔÛȷ΋ ·¿ÓÙËÛË, Ë ÔÔ›· ¤¯ÂÈ ·Ó·Ù˘¯ı› ‹‰Ë ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ· (4,8,9). ∏ ¤ÎıÂÛË, ÏÔÈfiÓ, Û ·Ïfi ÔÏ˘Û·Î¯·ÚȉÈÎfi ·ÓÙÈÁfiÓÔ/ÂÌ‚fiÏÈÔ (T-independent antigen) ‰ÈÂÁ›ÚÂÈ Ù· ·ÓÂÓÂÚÁ¿ µ ·ÙÙ·Ú· Ù· ÔÔ›· ·Ú¿ÁÔ˘Ó Î˘Ú›ˆ˜ IgG ·ÓÙÈÛÒÌ·Ù·, ‚Ú·¯˘¯ÚfiÓÈ·. ∆· µ ·˘Ù¿ ·ÙÙ·Ú· ‰ÂÓ ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ÌÓËÌÔÓÈο ·ÙÙ·Ú· (2,8,9,10,12). ∆· Û˘˙¢Á̤ӷ ÔÏ˘Û·Î¯·ÚȉÈο ·ÓÙÈÁfiÓ· (Tdependent antigens) ‰ÈÂÁ›ÚÔ˘Ó Â›Û˘ Ù· ·ÓÂÓÂÚÁ¿ µ ·ÙÙ·Ú· ̤ۈ Ì˯·ÓÈÛÌÔ‡ Ô˘ ··ÈÙ› ΢ÙÙ·ÚÈΤ˜ Î·È ÌÔÚȷΤ˜ ·ÏÏËÏÂȉڿÛÂȘ, ÂÂÍÂÚÁ·Û›· ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ·fi Ù· ·ÓÙÈÁÔÓÔ·ÚÔ˘ÛÈ·ÛÙÈο ·ÙÙ·Ú· (antigen-presenting cells - ∞PCs), ·ÚÔ˘Û›·ÛË ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ÛÙ· ∆-·ÙÙ·Ú· ̤ۈ MHC ÌÔÚ›ˆÓ, ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ∆-helper (CD4) ΢ÙÙ¿ÚˆÓ Î·È ¤ÎÎÚÈÛË Î˘ÙÙ·ÚÔÎÈÓÒÓ Ô˘ Ô‰ËÁÔ‡Ó Û ˆÚ›Ì·ÓÛË Ù· Thelper ·ÙÙ·Ú· Î·È ‚ÔËıÔ‡Ó ÙËÓ ÂÈÎÔÈÓˆÓ›· ÌÂٷ͇ Ï¢ÎÔ΢ÙÙ¿ÚˆÓ, ̤ۈ ÈÓÙÂÚÏ¢ÎÈÓÒÓ Ô˘ Ú˘ıÌ›˙Ô˘Ó ÙËÓ ·ÓÔÛȷ΋ ·¿ÓÙËÛË (2,5,6,8,12). ŸÙ·Ó Ù· µ ·ÙÙ·Ú· ÂÓÂÚÁÔÔÈËıÔ‡Ó, ÔÏÏ·Ï·ÛÈ¿˙ÔÓÙ·È Î·È ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ϷÛÌ·ÙÔ·ÙÙ·Ú· (ÂÎÎÚ›ÓÔ˘Ó ÂȉÈο ·ÓÙÈÛÒÌ·Ù·) Î·È Û ̷ÎÚfi‚È· ÌÓËÌÔÓÈο µ ·ÙÙ·Ú· Ì ÂÈÊ·ÓÂÈ·ÎÔ‡˜ ˘Ô‰Ô¯Â›˜ ·ÓÔÛÔÛÊ·ÈÚÈÓÒÓ ÂȉÈÎÒÓ ÁÈ· ÙÔ ·ÓÙÈÁfiÓÔ (2,7,8). ™ÙËÓ ÚˆÙÔÁÂÓ‹ ·ÓÔÛȷ΋ ·¿ÓÙËÛË ÚÔ˜ ·ÓÙÈÁfiÓÔ ÂÌ‚ÔÏ›Ô˘, ˘¿Ú¯ÂÈ ÌÈ· Ï·Óı¿ÓÔ˘Û· ÂÚ›Ô‰Ô˜ ÔÚÈÛÌ¤ÓˆÓ ËÌÂÚÒÓ ÒÛÔ˘ Ó· ÎÈÓËÙÔÔÈËıÔ‡Ó Ë Î˘ÙÙ·ÚÈ΋ Î·È Ë ¯˘ÌÈ΋ ·ÓÔÛ›·. ∆· ·ÓÙÈÛÒÌ·Ù· ÛÙÔÓ ÔÚfi ·ÓȯÓ‡ÔÓÙ·È 7-10 Ë̤Ú˜ ‹ Î·È Ï¤ÔÓ ÌÂÙ¿ ÙÔÓ ÂÌ‚ÔÏÈ·ÛÌfi (6,13). √ Ù‡Ô˜ ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÔÈΛÏÏÂÈ ·Ó¿ÏÔÁ· Ì ÙÔÓ Ù‡Ô ÙÔ˘ ·ÓÙÈÁfiÓÔ˘. ™ÙËÓ ÚÒÙË Â·Ê‹, Ù· ·Ú¯Èο ·ÓÙÈÛÒÌ·Ù· Â›Ó·È IgM. ∆· ÂfiÌÂÓ· ·ÓÙÈÛÒÌ·Ù· Â›Ó·È IgG. ∆· ÚÒÈÌ· IgM Î·È πgG ·ÓÙÈ-
ÛÒÌ·Ù· ÂÎÎÚ›ÓÔÓÙ·È ·fi Ù· B ÏÂÌÊÔ·ÙÙ·Ú· Û ·¿ÓÙËÛË ÚÔ˜ Ù· T-dependent antigens. ¶ÚÒÙ· ·ÓȯÓ‡ÔÓÙ·È Ù· πgM, Ù· ÔÔ›· ‰ÂÛÌÂ‡Ô˘Ó ÙÔ Û˘Ìϋڈ̷ Ô˘ ‰È¢ÎÔχÓÂÈ ÙË Ï‡ÛË Î·È ÙË Ê·ÁÔ΢ÙÙ¿ÚˆÛË ÙˆÓ ÌÈÎÚÔ‚›ˆÓ. ∫·Ù¿ ÙË 2Ë Â‚‰ÔÌ¿‰· ÂÏ·ÙÙÒÓÔÓÙ·È ÔÈ Ù›ÙÏÔÈ ÙˆÓ πgM Î·È ·˘Í¿ÓÔÓÙ·È ÔÈ Ù›ÙÏÔÈ ÙˆÓ IgG Ì ̤ÁÈÛÙ˜ ÙÈ̤˜ ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ ÂÓÙfi˜ 2-6 ‚‰ÔÌ¿‰ˆÓ. ∏ ÌÂÙ·‚ÔÏ‹ ÛÙË Û‡ÓıÂÛË ·fi πgM Û IgG ··ÈÙ› Û˘ÓÂÚÁ·Û›· B Î·È T ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ∆· IgG ·Ú¿ÁÔÓÙ·È ÛÙË Û˘Ó¤¯ÂÈ· Û ˘„ËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ Î·È ÚÔÛÙ·ÙÂ‡Ô˘Ó ·fi ÙȘ ÏÔÈÌÒÍÂȘ. √È ÏÂÈÙÔ˘ÚÁ›Â˜ ÙÔ˘˜ ·ÊÔÚÔ‡Ó Û˘Ó¿ÊÂÈ· ÚÔ˜ ÙÔ˘˜ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜, ÂÍÔ˘‰ÂÙ¤ÚˆÛË ÙˆÓ ÈÒÓ, ·ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ·ÓÙÈÁfiÓˆÓ, ·‰Ú·ÓÔÔ›ËÛË ÙÔÍÈÎÒÓ ÚÔ˚fiÓÙˆÓ, ·ÚÂÌfi‰ÈÛË Ù˘ ÚÔÛÎfiÏÏËÛ˘ ÙˆÓ ÌÈÎÚÔ‚›ˆÓ ÛÙÔ˘˜ ‚ÏÂÓÓÔÁfiÓÔ˘˜, ÚÔ·ÁˆÁ‹ Ù˘ Ê·ÁÔ΢ÙÙ¿ÚˆÛ˘, Û‡Ó‰ÂÛË ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ (6,8,14). ªÈ· ‰Â‡ÙÂÚË ¤ÎıÂÛË ÛÙÔ ›‰ÈÔ T-dependent ·ÓÙÈÁfiÓÔ Ô‰ËÁ› Û ÂÓÈÛ¯˘Ì¤ÓË ·ÓÔÛȷ΋ ·¿ÓÙËÛË. ŸÙ·Ó Ù· ÌÓËÌÔÓÈο µ ·ÙÙ·Ú· Û˘Ó·ÓÙÔ‡Ó ÙÔ ÂȉÈÎfi ·ÓÙÈÁfiÓÔ Ô˘ ÚÔοÏÂÛ ÙËÓ ·Ú·ÁˆÁ‹ ÙÔ˘˜, ÔÏÏ·Ï·ÛÈ¿˙ÔÓÙ·È Î·È ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ϷÛÌ·ÙÔ·ÙÙ·Ú· Ù·¯‡ÙÂÚ· ·fi fi,ÙÈ Ù· ·ÓÂÓÂÚÁ¿ ·ÙÙ·Ú·. ∏ ‰Â˘ÙÂÚÔÁÂÓ‹˜ ·˘Ù‹ ·¿ÓÙËÛË Â›Ó·È Ù·¯‡ÙÂÚË Î·È ÂÎχÂÙ·È ÂÓÙfi˜ 4-5 ËÌÂÚÒÓ. ∂›Ó·È ·ÔÙ¤ÏÂÛÌ· ·ÓÔÛȷ΋˜ ÌÓ‹Ì˘ ̤ۈ ÙˆÓ T Î·È B ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Î·È ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ¤ÓÙÔÓÔ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ µ ΢ÙÙ¿ÚˆÓ Ô˘ ·Ú¿ÁÔ˘Ó ·ÓÙÈÛÒÌ·Ù· ‹ ÙˆÓ ‰Ú·ÛÙÈÎÒÓ T ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ∆· T-independent ·ÓÙÈÁfiÓ· (·Ï¿ ÔÏ˘Û·Î¯·ÚȉÈο) ‰ÂÓ ÂÎÏ‡Ô˘Ó Ù¤ÙÔÈ· ¤ÓÙÔÓË ·ÓÔÛȷ΋ ·¿ÓÙËÛË (2,6-9). ∆· Ï·ÛÌ·ÙÔ·ÙÙ·Ú· ÌÔÚ› Ó· Â›Ó·È ‚Ú·¯‡‚È·. ÕÚ·, ··ÈÙÂ›Ù·È Û˘Ó¯‹˜ ÔÏÏ·Ï·ÛÈ·ÛÌfi˜ Î·È ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÌÓËÌÔÓÈÎÒÓ µ-΢ÙÙ¿ÚˆÓ Û ϷÛÌ·ÙÔ·ÙÙ·Ú· ÁÈ· Û˘Ó¯‹ ÚÔÛÙ·Û›·. ∞˘Ùfi ÌÔÚ› Ó· Á›ÓÂÙ·È ·˘ÙfiÌ·Ù· ‹ ̤ۈ Û˘Ó¯ԇ˜ ·ÓÙÈÁÔÓÈÎÔ‡ ÂÚÂıÈÛÌÔ‡ [ÊÔÚ›˜, ¤ÎıÂÛË Û ΢ÙÙ·ÚÔΛÓ˜ Ô˘ ·Ú¿ÁÔÓÙ·È ·fi ∆ ·ÙÙ·Ú· ÏfiÁˆ ÂÚÂıÈÛÌÔ‡ ·fi ‰È¿ÊÔÚ· ·ÓÙÈÁfiÓ· (bystander effect)] (EÈÎ. 1-5) (2,6,15,16). ∏ Ì·ÎÚ¿ ·Ú·ÌÔÓ‹ ÚÔÛٷ٢ÙÈÎÒÓ Ù›ÙÏˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÚÔÊ˘Ï¿ÛÛÂÈ ·fi ‰ÈÂÈÛ‰˘ÙÈΤ˜ ÏÔÈÌÒÍÂȘ Î·È Ë ·Ú·ÌÔÓ‹ ·˘Ù‹ Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È ·Ó·Áη›·. ¶·ÚfiÏÔ Ô˘ Ë ÌÓ‹ÌË ˘¿Ú¯ÂÈ, Ê·›ÓÂÙ·È fiÙÈ Ù· µ ÌÓËÌÔÓÈο ·ÙÙ·Ú· ÂÓ›ÔÙ ‰ÂÓ Â·ÚÎÔ‡Ó ·fi ÌfiÓ· ÙÔ˘˜, ÂÓÒ ¿ÏϘ ÊÔÚ¤˜ ÚÔÛÙ·ÙÂ‡Ô˘Ó Î·È Ì ÌÈÎÚfiÙÂÚÔ˘˜ ·ÎfiÌË Ù›ÙÏÔ˘˜ (17). ™ÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË, Ë ·¿ÓÙËÛË ÛÙ· ÂÌ‚fiÏÈ· ÂÎÙÈÌ¿Ù·È ·fi ÙÔ˘˜ Ù›ÙÏÔ˘˜ ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÛÙÔÓ ÔÚfi. √È ˘ÎÓfiÙËÙ˜ ·˘Ù¤˜, fï˜, Â›Ó·È ÌfiÓÔ Ì›· ·Ú¿ÌÂÙÚÔ˜ Ù˘ ·ÓÔÛȷ΋˜ ·¿ÓÙËÛ˘. ∏ ΢ÙÙ·ÚÈ΋ ·ÓÔÛ›· ·›˙ÂÈ Â›Û˘ ÚfiÏÔ. ∏ ·Ó·ÌÓËÛÙÈ΋ ·¿ÓÙËÛË Û ·ÓÂÌ‚ÔÏÈ·ÛÌÔ‡˜ ÛËÌ·›ÓÂÈ ·ÓÔÛȷ΋ ÌÓ‹ÌË ¶·È‰È·ÙÚÈ΋ 2009;72:23-28
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·26
26
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Î·È ¿Ú· ˘¿Ú¯Ô˘Û· Î·È ÂÌ̤ÓÔ˘Û· ·ÓÔÛ›·. ∂›Û˘, Ë ·Ô˘Û›· ·ÓȯÓ‡ÛÈÌˆÓ Ù›ÙÏˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ‰ÂÓ ÛËÌ·›ÓÂÈ Î·Ù’ ·Ó¿ÁÎË fiÙÈ ÙÔ ¿ÙÔÌÔ ‰ÂÓ ÚÔÛٷهÂÙ·È. √È Ì˯·ÓÈÛÌÔ› Â›Ó·È È‰È·›ÙÂÚ· Û‡ÓıÂÙÔÈ (2, 6,17,18). ªÂϤÙ˜ Û ·È‰È¿ Ô˘ ÂÌ‚ÔÏÈ¿ÛıËÎ·Ó Î·Ù¿ ÙÔ˘ Hib ·ÏÏ¿ Î·È Î·Ù¿ ÙÔ˘ Men C Ì ÙÔ Û˘˙¢Á̤ÓÔ ÂÌ‚fiÏÈÔ ¤‰ÂÈÍ·Ó fiÙÈ Ô ‚·ÛÈÎfi˜ ÂÌ‚ÔÏÈ·ÛÌfi˜ ‰ÂÓ Â·ÚΛ Î·È fiÙÈ ¤Ó· ¯ÚfiÓÔ Î·È Ï¤ÔÓ ÌÂÙ¿ ÙÔÓ ·Ú¯ÈÎfi ÂÌ‚ÔÏÈ·ÛÌfi Ë ÚÔÛÙ·Û›· ‹Ù·Ó ÌÈÎÚfiÙÂÚË, Û ۯ¤ÛË Ì ÙÔ ¿ÌÂÛÔ ÌÂÙ¿ ÙÔÓ ÂÌ‚ÔÏÈ·ÛÌfi ‰È¿ÛÙËÌ·, ·ÚfiÏÔ Ô˘ ˘‹Ú¯Â ·Ú¯È΋ ‰È¤ÁÂÚÛË. ∂›Û˘, Û ÔÏÏ¿ ¿ÙÔÌ· Ù· ·ÓÙÈÛÒÌ·Ù· ‹Ù·Ó ÔÚȷο ·ÎfiÌË Î·È Û ÎÔÓÙÈÓ¿ Ì ÙÔ Ù¤ÏÔ˜ Ù˘ ‚·ÛÈ΋˜ ÛÂÈÚ¿˜ ‰È·ÛÙ‹Ì·Ù·. ∞˘Ùfi ÛËÌ·›ÓÂÈ fiÙÈ Ù· ¿ÙÔÌ· ·˘Ù¿ ‰ÂÓ ÚÔÛٷهÔÓÙ·È Û ÌÈ· Ù·¯Â›· ÂÈÛ‚ÔÏ‹ ÙˆÓ ·ıÔÁfiÓˆÓ. Ÿˆ˜ ÚԷӷʤÚıËÎÂ, Ë ‰Â˘ÙÂÚÔÁÂÓ‹˜ ·ÓÔÛȷ΋ ·¿ÓÙËÛË Î·È Ë ÂÌÊ¿ÓÈÛË IgG ·ÓÙÈÛˆÌ¿ÙˆÓ ··ÈÙ› ÙÔ˘Ï¿¯ÈÛÙÔÓ 4 Ë̤Ú˜ ·ÎfiÌË Î·È Û ÂΛÓÔ˘˜ Ô˘ ›¯·Ó ··ÓÙ‹ÛÂÈ ÈηÓÔÔÈËÙÈο ÛÙËÓ ÚÒÙË Â·Ê‹ Ì ÙÔ ·ÓÙÈÁfiÓÔ. ™˘ÓÂÒ˜, ÙÔ priming ‰ÂÓ Â·ÚΛ ÌÂÚÈΤ˜ ÊÔÚ¤˜ Î·È Ù· ¿ÙÔÌ· ÌÔÚ› Ó· ÌËÓ ÚÔÛٷهÔÓÙ·È, ·Ó Î·È ÂÓ›ÔÙ ˘¿Ú¯ÂÈ ·ÏÏËÏÔÂÈÎ¿Ï˘„Ë ÚˆÙÔÁÂÓÔ‡˜ Î·È ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ··ÓÙ‹Ûˆ˜, Ô˘ ηχÙÂÈ ÙÔ ÎÂÓfi ¤ˆ˜ ÙËÓ ·Ú·ÁˆÁ‹ ·ÓÙÈۈ̿وÓ. ∏ ÚˆÙÔÁÂÓ‹˜ ·¿ÓÙËÛË Â›Ó·È ¤Ó· Û‡ÓıÂÙÔ Ê·ÈÓfiÌÂÓÔ, ÙÔ˘ ÔÔ›Ô˘ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ‰ÂÓ ·ÓÙÈηÙÔÙÚ›˙ÂÙ·È Ï‹Úˆ˜ ·fi Ì›· ·Ï‹ ̤ÙÚËÛË ·ÓÙÈÛˆÌ¿ÙˆÓ ÌÂÙ¿ ‰fiÛÂȘ ·Ó·˙ˆ‡ÚˆÛ˘. ™ËÌ·ÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ù˘ ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ·ÓÙÈۈ̷ÙÈ΋˜ ·¿ÓÙËÛ˘ Â›Ó·È Ë ÔÈfiÙËÙ· ÙˆÓ ·Ú·ÁfiÌÂÓˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ (ÈÛÔÙ˘›·, Û˘ÁÁ¤ÓÂÈ·, ÌÈÎÚÔ‚ÈÔÎÙfiÓ· ‰Ú¿ÛË), ηıÒ˜ Î·È Ë ÎÈÓËÙÈ΋ ÙÔ˘˜. ŒÙÛÈ, ‰ÂÓ Â›Ó·È ÂÚ›ÂÚÁÔ Ô˘ Û ÔÚÈṲ̂ӷ ¿ÙÔÌ· Ë ·ÓÔÛȷ΋ ÌÓ‹ÌË ·ÔÙ˘Á¯¿ÓÂÈ Ó· ÚÔÛʤÚÂÈ ÚÔÛÙ·Û›·. ™Ù· ¿ÙÔÌ· ·˘Ù¿, ÛËÌ·ÓÙÈÎfiÙÂÚË ·fi ÙËÓ ·Ú¯È΋ ·¿ÓÙËÛË Â›Ó·È Ë ÈηÓfiÙËÙ¿ ÙÔ˘˜ Ó· Û˘ÓÙËÚÔ‡Ó ÚÔÛٷ٢ÙÈο ›‰· ·ÓÙÈÛˆÌ¿ÙˆÓ Â› Ì·ÎÚfiÓ. ∏ ηٷÓfiËÛË Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ µ ΢ÙÙ¿ÚˆÓ ›Ûˆ˜ ‚ÔËı‹ÛÂÈ ÛÙËÓ Î·Ù·ÓfiËÛË Ù˘ Û¯¤Û˘ ÂÌ‚fiÏÈÔ-ÚˆÙÔÁÂÓ‹˜ ·¿ÓÙËÛË-Û˘Ó¯‹˜ ·Ú·ÁˆÁ‹ ·ÓÙÈÛˆÌ¿ÙˆÓ (2,5,7,19,20). ∏ Û˘Ó¿ÊÂÈ· (avidity) Â›Ó·È Î·Ïfi˜ ‰Â›ÎÙ˘ Û˘ÁÁ¤ÓÂÈ·˜ (affinity) ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÁÈ· ¤Ó· Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÓÙÈÁfiÓÔ. ∏ Û˘Ó¿ÊÂÈ· ·˘Í¿ÓÂÈ ÌÂÙ¿ ¤ÎıÂÛË Û T-dependent ·ÓÙÈÁfiÓ· Î·È Ë ·‡ÍËÛË ·˘Ù‹ ‰ËÏÒÓÂÈ ÙËÓ ÈηÓfiÙËÙ· ·Ú·ÁˆÁ‹˜ µ ΢ÙÙ¿ÚˆÓ ˘„ËÏ‹˜ Û˘ÁÁ¤ÓÂÈ·˜, ‰ËÏ. ÙËÓ ·Ú·ÁˆÁ‹ ÈÔ ÔÈÔÙÈÎÒÓ Î·È ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈÎÒÓ ·ÓÙÈۈ̿وÓ. ¶·Ú·Ì¤ÓÂÈ, fï˜, ·Û·Ê¤˜ ·Ó ÔÈ Û¯ÂÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÛÙËÓ avidity ÌÂÙ·ÊÚ¿˙ÔÓÙ·È Û ‰È·ÊÔÚ¤˜ ÛÙË Ì·ÎÚÔ¯ÚfiÓÈ· ÚÔÛÙ·Û›· (2,5,7,21,22). √ ÂÌ‚ÔÏÈ·ÛÌfi˜ ÚÔηÏ› ÌÂÁ¿ÏË ·‡ÍËÛË Ï·ÛÌ·ÙÔ΢ÙÙ¿ÚˆÓ Î·È ÌÓËÌÔÓÈÎÒÓ µ ΢ÙÙ¿ÚˆÓ. ∏ ·‡Paediatriki 2009;72:23-28
ÍËÛË ÙˆÓ Ï·ÛÌ·ÙÔ΢ÙÙ¿ÚˆÓ Â›Ó·È ·ÚÔ‰È΋ Î·È ÁÈ’ ·˘Ùfi ÛÙ· ÂӉȿÌÂÛ· ÙˆÓ ·ÓÙÈÁÔÓÈÎÒÓ ÂÎı¤ÛÂˆÓ ‰È·ÛÙ‹Ì·Ù· ··ÈÙÂ›Ù·È ·Ó·Ó¤ˆÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÁÈ· ‰È·Ù‹ÚËÛË ÈηÓÔÔÈËÙÈÎÒÓ ÂȤ‰ˆÓ. ∆Ô ÙÈ ¯ÚÂÈ¿˙ÂÙ·È Î·È ÔÈ· Â›Ó·È Ù· ÂÚÂı›ÛÌ·Ù· Ô˘ ‚ÔËıÔ‡Ó ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÌÓËÌÔÓÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Û ϷÛÌ·ÙÔ·ÙÙ·Ú· Î·È ÛÙË Û˘ÓÙ‹ÚËÛË ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ Â›Ó·È ·Û·Ê¤˜. ¶ÔÈ· Â›Ó·È Ë Ê‡ÛË Ù˘ ÌÓ‹Ì˘ Î·È ÙˆÓ Ï·ÛÌ·ÙÔ΢ÙÙ¿ÚˆÓ Ô˘ ·Ú¿ÁÔÓÙ·È ·fi ÂÌ‚ÔÏÈ·ÛÌfi ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ·; ¶Ò˜ ÌÂÙ·‚¿ÏÏÔÓÙ·È ÔÈ ··ÓÙ‹ÛÂȘ ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· ‹ ÌÂÙ¿ ÙË ‰fiÛË ÂÌ‚ÔÏ›Ô˘ ·Ó·˙ˆ‡ÚˆÛ˘; ¶ÔÈ· µ-·ÙÙ·Ú· ÔÏÏ·Ï·ÛÈ¿˙ÔÓÙ·È Ì¤Ûˆ ÙÔ˘ bystander effect Î·È ÔÈ· ̤ۈ ÙÔ˘ ÂÌ‚ÔÏÈ·ÛÌÔ‡; ∏ ÁÓÒÛË ı· ‹Ù·Ó ÎÏÂȉ› ÁÈ· ÙËÓ Î·Ù·ÓfiËÛË Ù˘ ‚ÈÔÏÔÁ›·˜ ÙˆÓ Û˘˙¢ÁÌ¤ÓˆÓ ÔÏ˘Û·Î¯·ÚȉÈÎÒÓ ÂÌ‚ÔÏ›ˆÓ, ÌÈ·˜ Î·È Ë ÚˆÙÔÁÂÓ‹˜ ·¿ÓÙËÛË Ê·›ÓÂÙ·È fiÙÈ ‰ÂÓ Â·ÚΛ ϤÔÓ ÁÈ· ÚÔÛÙ·Û›· ÔÚÈÛÌ¤ÓˆÓ ·ÙfiÌˆÓ Ì ¤ÏÏÂÈ„Ë ·ÓÙÈÛˆÌ¿ÙˆÓ Û ‰Â‰Ô̤ÓË ÛÙÈÁÌ‹ (2). ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ Ì ·ÓÙÈۈ̷ÙÈÎfi ¤ÏÂÁ¯Ô ÚÔ ÙÔ˘ ÂÌ‚ÔÏÈ·ÛÌÔ‡ Î·È ÌÂÙ¿ ÙÔÓ ÂÌ‚ÔÏÈ·ÛÌfi ÌÂ Û˘˙¢Á̤ÓÔ ÂÌ‚fiÏÈÔ Î·Ù¿ ÙÔ˘ Hib ¤‰ÂÈÍ·Ó ·˘Ùfi ·ÎÚÈ‚Ò˜, fiÙÈ ‰ËÏ. Ë ÚˆÙÔÁÂÓ‹˜ Î·È ÌfiÓÔ ·¿ÓÙËÛË ÌÔÚ› Ó· ÌËÓ ÚÔÛٷهÂÈ Â·ÚÎÒ˜. ∂›Û˘, Â›Ó·È ÁÓˆÛÙfi fiÙÈ Û ¿ÙÔÌ· Ì ¯ÔÚ‹ÁËÛË Û˘Ó‰˘·Ṳ̂ÓÔ˘ ÂÌ‚ÔÏ›Ô˘ DTaP Î·È Hib ¤¯ÂÈ ·Ú·ÙËÚËı› ÌÂȈ̤ÓË ·ÓÔÛȷ΋ ·¿ÓÙËÛË. ∆ÂÏÂ˘Ù·›·, ÛÙË ª. µÚÂÙ·Ó›· ‰È·ÈÛÙÒıËΠÌÂȈ̤ÓË ÚÔÛÙ·Û›· ¤Ó· ¯ÚfiÓÔ Î·È Ï¤ÔÓ ·fi ÙÔ ÂÌ‚fiÏÈÔ ÁÈ· Men C, Û ۯ¤ÛË Ì ÂÚ›Ô‰Ô ÌÈÎÚfiÙÂÚË ÙÔ˘ ¤ÙÔ˘˜ ·fi ÂÌ‚ÔÏÈ·ÛÌfi. √È ·ÔÙ˘¯›Â˜ Î·È ÛÙ· ‰‡Ô ÂÌ‚fiÏÈ· ‹Ù·Ó Û ¿ÙÔÌ· Ô˘ ·Ô‰ÂÈÁ̤ӷ ›¯·Ó ÚˆÙÔÁÂÓ‹ ·¿ÓÙËÛË, ·ÏÏ¿ ÛÙË Û˘Ó¤¯ÂÈ· ÔÈ Ù›ÙÏÔÈ ÙˆÓ ·ÓÙÈη„ȉÈÎÒÓ ÙÔ˘˜ ·ÓÙÈÛˆÌ¿ÙˆÓ ‹Ù·Ó ¯·ÌËÏfiÙÂÚÔÈ ·fi ÙÔ˘˜ ıˆÚÔ‡ÌÂÓÔ˘˜ ˆ˜ ÚÔÛٷ٢ÙÈÎÔ‡˜. º˘ÛÈο, Ù· ¿ÙÔÌ· ·˘Ù¿ Â›Ó·È ·ÚÔÛÙ¿ÙÂ˘Ù· ·fi Ïԛ̈ÍË Ù·¯Â›·˜ ÂͤÏÈ͢ ÚÈÓ ÚÔÏ¿‚ÂÈ Ó· ··ÓÙ‹ÛÂÈ Ô ·ÓÔÛÔÏÔÁÈÎfi˜ Ì˯·ÓÈÛÌfi˜ (2,23,24,25,26). ŸÛÔÓ ·ÊÔÚ¿ ÙÔÓ ÌËÓÈÁÁÈÙȉfiÎÔÎÎÔ, ÚfiÛÊ·Ù˜ ¤Ú¢Ó˜ ¤‰ÂÈÍ·Ó Ù· ÂÍ‹˜: ‰È¿ÚÎÂÈ· ÚÔÛÙ·Û›·˜ ·fi ÙÔ ÂÌ‚fiÏÈÔ fi¯È ȉȷ›ÙÂÚ· ÁÓˆÛÙ‹, ÔÈ ‰Â›ÎÙ˜ ·ÓÔÛ›·˜ Î·È Ë ÚÔÛÙ·Û›· ÂÍ·ÛıÂÓÔ‡Ó Ù·¯¤ˆ˜ ÌÂÙ¿ ÙÔÓ ·Ú¯ÈÎfi ÂÌ‚ÔÏÈ·ÛÌfi, 4 ¯ÚfiÓÈ· ÌÂÙ¿ ‚·ÛÈÎfi ÂÌ‚ÔÏÈ·ÛÌfi ÙÔ 88% ¤¯ÂÈ Ù›ÙÏÔ˘˜ ¯·ÌËÏfiÙÂÚÔ˘˜ ÙˆÓ ÚÔÛٷ٢ÙÈÎÒÓ, ¯·ÌËÏ¿ ›‰· (ÌÂÙ¿ 3ÂÙ›·) Û ÂÌ‚ÔÏÈ·Ûı¤ÓÙ˜ ÌÂÙ¿ ÙÔÓ 1Ô ¯ÚfiÓÔ Ù˘ ˙ˆ‹˜, ·˘ÍË̤ÓË ÂÌ‚ÔÏÈ·ÛÙÈ΋ ·Ó·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· 2-3 ¯ÚfiÓÈ· ÌÂÙ¿ ÙÔÓ ‚·ÛÈÎfi ÂÌ‚ÔÏÈ·ÛÌfi (3,20,27). ™Â Ì›· ¤Ú¢ӷ (20), Ì¿ÏÈÛÙ·, ‚Ú¤ıËΠfiÙÈ ÌÂÙ¿ ·Ú¯ÈÎfi Û¯‹Ì· 3 ‰fiÛÂˆÓ (2, 3, 4 ÌËÓÒÓ) Ë ·ÓÙÈÁÔÓÈÎfiÙËÙ· ÂÌ‚ÔÏ›Ô˘, ·fi 93% ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ÌÂÙ¿ ÂÌ‚ÔÏÈ·ÛÌfi, ˘Ô¯ÒÚËÛ Û -81% ÛÙÔ ‰È¿ÛÙËÌ· ¤Ú·Ó ÙÔ˘ ¤ÙÔ˘˜. µ¤‚·È·, Ô ·ÚÈıÌfi˜ ·˘Ùfi˜ ÛÙËÚ›¯ıËÎÂ
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·27
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¶ÔÏ˘Û·Î¯·ÚȉÈο ·ÓÙÈÁfiÓ· – Û˘˙¢Á̤ӷ ÂÌ‚fiÏÈ·
Û 19 ÂÚÈÙÒÛÂȘ ‰ÈÂÈÛ‰˘ÙÈ΋˜ ÌËÓÈÁÁÈÙȉÔÎÔÎÎÈ΋˜ ÓfiÛÔ˘ C, οÙÈ Ô˘ ÛËÌ·›ÓÂÈ fiÙÈ ÁÈ· Ï‹ÚË ÙÂÎÌËÚ›ˆÛË ¯ÚÂÈ¿˙ÂÙ·È ÌÂÁ·Ï‡ÙÂÚÔ˜ ·ÚÈıÌfi˜. °ÂÓÈο, fï˜, ıˆÚÂ›Ù·È Û‹ÌÂÚ· fiÙÈ ÙfiÛÔ ÁÈ· ÙÔÓ ·ÈÌfiÊÈÏÔ fiÛÔ Î·È ÁÈ· ÙÔÓ ÌËÓÈÁÁÈÙȉfiÎÔÎÎÔ, Ë ·ÓÔÛÔÏÔÁÈ΋ ÌÓ‹ÌË ‰ÂÓ Â›Ó·È Â·Ú΋˜ ÁÈ· Ó· ÚÔÛٷهÛÂÈ ÔÚÈṲ̂ӷ ÂÌ‚ÔÏÈ·Ṳ̂ӷ ¿ÙÔÌ·. √ ΛӉ˘ÓÔ˜ ÓfiÛËÛ˘ ηıÔÚ›˙ÂÙ·È ·fi ·Ú·Ì¤ÙÚÔ˘˜ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜, Ù˘ ÂÌ‚ÔÏÈ·ÛÙÈ΋˜ ·ÓÔÛ›·˜, Ù˘ ÂÍ¿ÏÂȄ˘ ÊÔÚ›·˜ Î·È Ù˘ ÚfiÎÏËÛ˘ ¤ÌÌÂÛ˘ ·ÓÔÛ›·˜ (2,3). ªÂ ÙÔ Ó¢ÌÔÓÈÔÎÔÎÎÈÎfi Û˘˙¢Á̤ÓÔ ÂÌ‚fiÏÈÔ ‰ÂÓ ¤¯ÂÈ ÚÔ·„ÂÈ ÚÔ˜ ÙÔ ·ÚfiÓ È‰È·›ÙÂÚÔ Úfi‚ÏËÌ·, ÌÈ·˜ Î·È ÔÈ ÂÊ·ÚÌÔ˙fiÌÂÓ˜ ‰fiÛÂȘ Â›Ó·È ·ÚÎÂÙ¤˜, ·ÏÏ¿ Î·È ÁÈ· ÙȘ ÌÂÁ·Ï‡ÙÂÚ˜ ËÏÈ˘ ˘¿Ú¯ÂÈ ÙÔ 23‰‡Ó·ÌÔ ÔÏ˘Û·Î¯·ÚȉÈÎfi ÂÌ‚fiÏÈÔ. ¶ÚÔ·ÙÂÈ ÏÔÈfiÓ ÙÔ Ú·ÎÙÈÎfi ÂÚÒÙËÌ·: ÔÈÔ Â›Ó·È ÙÔ ÛˆÛÙfi ‰ÔÛÔÏÔÁÈÎfi Û¯‹Ì· ÁÈ· Ù· ÔÏ˘Û·Î¯·ÚȉÈο Û˘˙¢Á̤ӷ ÂÌ‚fiÏÈ·; ∆Ô ÂÚÒÙËÌ· ·ÊÔÚ¿ ΢ڛˆ˜ ÙÔ ÂÌ‚fiÏÈÔ ÙÔ˘ ÌËÓÈÁÁÈÙȉfiÎÔÎÎÔ˘, Ô˘ ÂÍ·Ú¯‹˜ ÂÊ·ÚÌfiÛıËΠ̠ÌÂȈ̤ӷ ‰ÔÛÔÏÔÁÈο Û¯‹Ì·Ù· Ô˘ Ô›ÎÈÏ·Ó ·fi 1 ¤ˆ˜ Î·È 3 ‰fiÛÂȘ. ∏ ·Ú¯È΋ ˘ÈÔı¤ÙËÛË ‹Ù·Ó 3 ‰fiÛÂȘ ÛÙÔÓ ‚·ÛÈÎfi ÂÌ‚ÔÏÈ·ÛÌfi (‚ÚÂÊÈ΋ ËÏÈΛ·) ‹ 1 ‰fiÛË ÌÂÙ¿ ÙËÓ ËÏÈΛ· ÙˆÓ 12 ÌËÓÒÓ (3,20,26,28). ∆· Û¯‹Ì·Ù· ·˘Ù¿ ÛÙËÚ›¯ıËÎ·Ó Û ·Ú¯ÈΤ˜ ÌÂϤÙ˜ ·ÓÔÛÔÁÔÓÈÎfiÙËÙ·˜ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ Î·È ˘ÈÔıÂÙ‹ıËÎ·Ó ·Ó¿ÏÔÁ· Ì ÙȘ ÂȉËÌÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ οı ¯ÒÚ·˜. MÂϤÙ˜ ÛÙË Û˘Ó¤¯ÂÈ· ¤‰ÂÈÍ·Ó fiÙÈ 2 ‰fiÛÂȘ ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ· ÚÔηÏÔ‡Ó ÈηÓÔÔÈËÙÈÎfi Ù›ÙÏÔ ·ÓÙÈۈ̿وÓ. ∫·Ù¿ Û˘Ó¤ÂÈ·, ·Ó ÂÊ·ÚÌÔ˙fiÙ·Ó ÙÔ Û¯‹Ì· ·˘Ùfi, ı· ÚԤ΢ÙÂ Î·È ÛËÌ·ÓÙÈÎfi ÔÈÎÔÓÔÌÈÎfi fiÊÂÏÔ˜. À‹ÚÍ·Ó Â›Û˘ ‰È·ÈÛÙÒÛÂȘ fiÙÈ Ë ‰È‡ڢÓÛË ÙÔ˘ ÌÂÛԉȷÛÙ‹Ì·ÙÔ˜ ‰fiÛÂˆÓ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ ηٿ ÙÔ˘ ·ÈÌÔÊ›ÏÔ˘ ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ· ‚ÂÏÙÈÒÓÂÈ ÙÔ priming Î·È ÙËÓ avidity Î·È ·˘Í¿ÓÂÈ ÙÔÓ ÙÂÏÈÎfi Ù›ÙÏÔ ·ÓÙÈÛˆÌ¿ÙˆÓ (2). TÔ fiÙÈ Ë ·ÓÔÛ›· ÂÍ·ÛıÂÓ› ÌÂÙ¿ ¿ÚÔ‰Ô ¯ÚfiÓÔ˘, fiˆ˜ ÚԷӷʤÚıËÎÂ, Ô‰‹ÁËÛ Û Ӥ˜ ÌÂϤÙ˜ 2 ‹ 3 ·Ú¯ÈÎÒÓ ‰fiÛÂˆÓ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ ηٿ ÙÔ˘ ÌËÓÈÁÁÈÙȉfiÎÔÎÎÔ˘ (ÌfiÓÔ˘ ‹ ÛÂ Û˘Ó‰˘·ÛÌÔ‡˜), ηıÒ˜ Î·È ¯ÔÚ‹ÁËÛ˘ ·Ó·ÌÓËÛÙÈ΋˜ ‰fiÛ˘ (29,30,31). √È ÌÂϤÙ˜ ·˘Ù¤˜ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ Û¯‹Ì· ÙˆÓ 2 ·Ú¯ÈÎÒÓ ‰fiÛÂˆÓ Â›Ó·È ·ÓÔÛÔÁÔÓÈÎfi Î·È ÚÔηÏ› ·ÓÔÛȷ΋ ÌÓ‹ÌË. ∂›Û˘, fiÙÈ Ë ·Ó·ÌÓËÛÙÈ΋ ‰fiÛË Â›Ó·È Î·Ù¿ÏÏËÏË ÁÈ· ÔÔÈÔ‰‹ÔÙ ‚·ÛÈÎfi Û¯‹Ì· ÂÌ‚ÔÏÈ·ÛÌÔ‡ Î·È Â›Û˘ ηٿÏÏËÏË Î·È ·ÓÔÛÔÁÔÓÈ΋ ÌÂÙ¿ ÙÔ Û¯‹Ì· ÙˆÓ 2 ‰fiÛÂˆÓ ÛÙÔÓ ‚·ÛÈÎfi ÂÌ‚ÔÏÈ·ÛÌfi (30,31). ŒÙÛÈ Î·ıÈÂÚÒıËΠÙÔ Û¯‹Ì· 2+1 (·fi ‚ÚÂÊÈ΋ ËÏÈΛ·) ‹ 1 ‰fiÛË fiÙ·Ó ÙÔ ÂÌ‚fiÏÈÔ Á›ÓÂÙ·È Û ËÏÈΛ· ¿Óˆ ÙˆÓ 12 ÌËÓÒÓ. ∞Ó Î·È Â›Ó·È Ôχ ÓˆÚ›˜ Ó· ·ÔÊ·Óı› ηÓ›˜ ÁÈ· ÙÔ ÔÈÔ Û¯‹Ì· ÌËÓÈÁÁÈÙȉÔÎÔÎÎÈÎÔ‡ ÂÌ‚ÔÏ›Ô˘ Â›Ó·È Î·Ï‡ÙÂÚÔ, ˘¿Ú¯Ô˘Ó Ù· ÂÍ‹˜ ‰Â‰Ô̤ӷ: ·) Ë ÌËÓÈÁ-
ÁÈÙȉÔÎÔÎÎÈ΋ ÓfiÛÔ˜ ·˘Ù‹ ηı·˘Ù‹ ‰ÂÓ ÚÔηÏ› ÈÛ¯˘Ú‹ ·ÓÔÛ›· ÛÙȘ ÌÈÎÚ¤˜ ËÏÈ˘, ‚) Ë Û˘¯ÓfiÙËÙ· Ù˘ ÓfiÛÔ˘ Â›Ó·È ·˘ÍË̤ÓË ÛÙËÓ ÂÊË‚È΋ ËÏÈΛ·, fiˆ˜ ·˘ÍË̤ÓË Â›Ó·È Î·È Ë ‚·Ú‡ÙËÙ· Û’ ·˘Ù‹Ó ÙËÓ ËÏÈÎȷ΋ ÂÚ›Ô‰Ô. ™Â Ú·ÎÙÈÎÔ‡˜ fiÚÔ˘˜, ÔÈ ‰fiÛÂȘ ·Ó·˙ˆ‡ÚˆÛ˘ ÁÈ· Ù· Û˘˙¢Á̤ӷ ÂÌ‚fiÏÈ· Â›Ó·È ›Ûˆ˜ Ô ÈÔ Î·Ù¿ÏÏËÏÔ˜ ÙÚfiÔ˜ ‚ÂÏÙ›ˆÛ˘ Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ¿˜ ÙÔ˘˜. ∫¿ÙÈ Ô˘ ‹Ù·Ó ¿ÁÈ· ¿Ô„‹ Ì·˜ ·fi ÂÙÒÓ (32). µ¤‚·È·, ˘¿Ú¯Ô˘Ó ·ÎfiÌË ÚÔ‚Ï‹Ì·Ù· ÛÙÔ fiÙÂ Î·È ÛÙÔ Ò˜ ÁÈ· ÙȘ ‰fiÛÂȘ ·˘Ù¤˜. ∏ ¯Ú‹ÛË ÙˆÓ ÔÏ˘‰‡Ó·ÌˆÓ ÂÌ‚ÔÏ›ˆÓ Ô˘ ÂÍ·ÛıÂÓÔ‡Ó ÙËÓ ·ÓÙÈۈ̷ÙÈ΋ ·¿ÓÙËÛË Î¿ÔÈˆÓ ‰fiÛˆÓ, .¯. Ù˘ ‰Â‡ÙÂÚ˘ ‰fiÛ˘ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ ÙÔ˘ ·ÈÌfiÊÈÏÔ˘ ÈÓÊÏÔ˘¤ÓÙ˙·˜ Ù‡Ô˘ b (24,26,33,34), ¯ˆÚ›˜ ÚÔ˜ ÙÔ ·ÚfiÓ ÎÏÈÓÈΤ˜ Û˘Ó¤ÂȘ, Î·È Ë ÌÂȈ̤ÓË ‰˘Ó·ÙfiÙËÙ· Ê˘ÛÈ΋˜ ·Ó·˙ˆ‡ÚˆÛ˘ Ô˘ ı· ·Ú·ÙËÚËı› Ù· ÂfiÌÂÓ· ¯ÚfiÓÈ· (·ÎÚÈ‚Ò˜ ÏfiÁˆ Ù˘ ¯Ú‹Û˘ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ) ‰ËÌÈÔ˘ÚÁÔ‡Ó ÙÔ ÂÚÒÙËÌ· ÙÔ˘ Ò˜ ı· Û˘ÓÙËÚËı› Ë Ì·ÎÚÔ¯ÚfiÓÈ· ·ÓÔÛ›· Ô˘ ··ÈÙÂ›Ù·È ÁÈ· Ù· ÔÏ˘Û·Î¯·ÚȉÈο ·ÓÙÈÁfiÓ·. ª‹ˆ˜ Ì ·ÎfiÌË ÂÚÈÛÛfiÙÂÚ˜ ‰fiÛÂȘ; ¶ÈÛÙ‡ԢÌ fiÙÈ ÔÈ ·Ó·ÌÓËÛÙÈΤ˜ ‰fiÛÂȘ Â›Ó·È ·Ó·Áη›Â˜, ›Ûˆ˜ ÂÚÈÛÛfiÙÂÚÔ ÙˆÓ ·Ú¯ÈÎÒÓ. £· ÌÔÚÔ‡Û·Ì ̿ÏÈÛÙ· Ó· Û˘˙ËÙ‹ÛÔ˘Ì ¤Ó· ÂÓÈ·›Ô Û¯‹Ì· Î·È ÁÈ· Ù· 3 Û˘˙¢Á̤ӷ ÔÏ˘Û·Î¯·ÚȉÈο ÂÌ‚fiÏÈ·: 3 ·Ú¯ÈΤ˜ ‰fiÛÂȘ ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ· (ı· ÌÔÚÔ‡Û·Ó Ó· Â›Ó·È 2) Û˘Ó 1 ·Ó·ÌÓËÛÙÈ΋ ‰fiÛË ÛÙËÓ ËÏÈΛ· ÙˆÓ 18 ÌËÓÒÓ Û˘Ó ·ÎfiÌË 1 ·Ó·ÌÓËÛÙÈ΋ ηٿ ÙËÓ Â›ÛÔ‰Ô ÛÙÔ ‰ËÌÔÙÈÎfi Û¯ÔÏÂ›Ô (6 ¯ÚfiÓˆÓ). ™Â ·È‰È¿ Ô˘ ÁÈ· οÔÈÔ ÏfiÁÔ ÍÂÎÈÓÔ‡Ó ÙÔÓ ÂÌ‚ÔÏÈ·ÛÌfi Û ËÏÈΛ· ¿Óˆ ÙˆÓ 12-24 ÌËÓÒÓ, ıˆÚԇ̠··Ú·›ÙËÙË ÙË ¯ÔÚ‹ÁËÛË 2 ‰fiÛˆÓ: 1 + 1 ηٿ ÙËÓ Â›ÛÔ‰Ô ÛÙÔ ‰ËÌÔÙÈÎfi Î·È ›Ûˆ˜ 1 ·ÎfiÌË ‰fiÛË Î·Ù¿ ÙËÓ Â›ÛÔ‰Ô ÛÙÔ Á˘ÌÓ¿ÛÈÔ. Œˆ˜ fiÙÔ˘, ‚¤‚·È·, ·˘Ù¿ Á›ÓÔ˘Ó Ú¿ÍË (Â¿Ó ˘ÈÔıÂÙËıÔ‡Ó), Ô ·È‰›·ÙÚÔ˜ ı· Ú¤ÂÈ Ó· ÂÊ·ÚÌfi˙ÂÈ ÙȘ Ô‰ËÁ›Â˜ ÙÔ˘ ÂıÓÈÎÔ‡ ÚÔÁÚ¿ÌÌ·ÙÔ˜ ÂÌ‚ÔÏÈ·ÛÌÔ‡, ‰ÈfiÙÈ ÌfiÓÔÓ ¤ÙÛÈ ÂÈÙ˘Á¯¿ÓÔÓÙ·È ÂÓÈ·›· ·ÔÙÂϤÛÌ·Ù·.
µÈ‚ÏÈÔÁÚ·Ê›· 1. Ada G. Vaccines and vaccination. NEJM 2001;345:10421053. 2. Kelly DF, Pollard AJ, Moxon ER. Immunological memory. The role of B cells in long term protection against invasive bacterial pathogens. JAMA 2005;294:3019-3023. 3. Snape MD, Pollard AJ. Meningococcal polysaccharideprotein conjugate vaccine. Lancet Infect Dis 2005;5:21-30. 4. Bilukha O, Messonnier N, Fischer ª. Use of meningococcal vaccines in the United States. Pediatr Infect Dis J 2007;26:371-376. 5. Mandel G, Bennett J, Delin R. Principles and practices of infectious diseases. 6th ed. Philapelphia: Elsevier; 2005. ¶·È‰È·ÙÚÈ΋ 2009;72:23-28
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6. Peter G. Immunization Practices. In: Behrman R, Kliegman R, Jenson H. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders Co; 2004. p. 1174. 7. Male D, Brostoff J, Roth D, Roitt I. Immunology. 7th ed. Philadelphia: Mosby Co; 2006. 8. Parkin J, Cohen B. An overview of the immune systema. Lancet 2001;357:1777-1789. 9. Burkley R. The T-, B-, and NK-cell systems. In Behrman R, Kliegman R, Jenson H. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: Saunders Co; 2004. p. 683. 10. Finn A. Bacterial polysaccharide-protein conjugate vaccines. Brit Med Bull 2004;70:1-14. 11. Bogaert D, Hermans P, Adrian P, Rumke H, deGroot R. Pneumococcal vaccines: an update on current strategies. Vaccine 2004;22:2209-2220. 12. Goldblatt D, Assari T, Snapper C. The immunobiology of polysaccharide and conjugate vaccinees. In: Pneumococcal vaccines by Siber, Klugman, Makela, editors. Washington: ASM Press; 2008. p. 67-82. 13. McVernon J, Johnson P, Pollard A, Slack M, Moxon E. Immunologic memory in H. influenzae type b conjugate vaccine failure. Arch Dis Child 2003;88:379-383. 14. Janeway C. How the immune system protects the host from infection. Microbes and Infection 2001;3:1167-1171. 15. Lucas A, Granoff D. Imperfect memory and the development of H. influenzae type b disease. Pediatr Inf Dis J 2001;20: 235-239. 16. Bernasconi N, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 2002;298:2199-2202. 17. Denoel P, Goldblatt D, de Vleeschauwer, Jacquet J-M, Pichichero M, Poolman J. Quality of the Haemophilus influenzae type b antibody response induced by diphtheriatetanus-acellular pertussis/Hib combination vaccines. Clin Vacc Immunol 2007;14:1362-1369. 18. MacLennan JM, Shackley F, Heath PT, Deeks JJ, Flamank C, Herbert M, et al. Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: a randomized controlled trial. JAMA 2000;283:2795-2801. 19. Trotter CL, McVernon J, Andrews NJ, Burrage M, Ramsay ME. Antibody to Haemophilus influenzae type b after routine and catch-up vaccination. Lancet 2003;361:15231524. 20. Trotter CL, Andrews NJ, Kaczmarski EB, Miller E, Ramsay ME. Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction. Lancet 2004;364:365-367. 21. Ekstrom N, Ahman H, Verho J, Jokinen J, Vakevainen M, Kilpi T, et al. Kinetics and avidity of antibodies evoked by heptavalent pneumococcal conjugate vaccines PncCRM
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and PncOMPC in the Finnish Otitis Media Vaccined Trial. Infect Immun 2005;73:369-377. 22. Richmond P, Borroe R, Goldblatt D. Ability of 3 different meningococcal C conjugate vaccines to induce immunologic memory after a single dose in UK toddlers. J Infect Dis 2001;183:160-163. 23. Heath PT, Ramsay ME. H. influenzae type b vaccine booster campaign. BMJ 2003;326:1158-1159. 24. McVernon J, Johnson PD, Pollard AJ, Slack MP, Moxon ER. Immunologic memory in Haemophilus influenezae type b conjugate vaccine failure. Arch Dis Child 2002;88:379-383. 25. McVernon J, Heath P. Reinforcement of Hib immunization required. Commun Dis Public Health 2003;6:2. 26. Finn A, Heath P. Conjugate vaccines. Arch Dis Child 2005; 90:667-669. 27. Borrow R, Goldblatt D, Andrew N, Southern J, Ashton L, Deane S, et al. Antibody persistence and immunological memory at age 4 years after meningococcal group C conjugate vaccination in children in the United Kingdom. J Infect Dis 2002;186:1353-1357. 28. English M, Mc Lennan J, Bowen-Morris J, Deeks J, Boardman M, Brown K, et al. A randomised, double-blind, controlled trial of the immunogenicity and tolerability of a meningococcal group C conjugate vaccine in young British infants. Vaccine 2001;19:1232-1238. 29. McLennan J, Shackley F, Heath P, Deeks J, Flamank C, Herbert M, et al. Safety, immunogenicity and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants. JAMA 2000;283:2795-2801. 30. Buttery J, Riddell A, McVernon J, Chantler T, Lane L, Bowen-Morris J, et al. Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants. JAMA 2005;293:1751-1758. 31. Tejedor J, Omenaca F, Garcia-Sicilia J, Verdaguer , Van Esso D, Esporrin C, et al. Immunogenicity and reactogenicity of a three-dose primary vaccination course with a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-haemophilus influenzae type b vaccine coadministered with a meningococcal C conjugate vaccine. Pediatr Infect Dis J 2004;23:1109-1115. 32. K·‚·ÏÈÒÙ˘ π. ÃÚÔÓÈÎfi 2003. £ÂÛÛ·ÏÔÓ›ÎË: ∂ΉfiÛÂȘ °È·¯Ô‡‰Ë; 2004. 33. Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist A. Combined vaccination of H. influenzae type b conjugated and diphtheria-tetanus-pertussis combined acellular vaccine. Lancet 1999;354:2063-2068. 34. McVernon J, Andrews N, Slack MP, Ramsay ME. Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis. Lancet 2003;361:1521-1523.
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ÃÔÚ‹ÁËÛË ‰‡Ô ·ÓÙÈ-TNF Û΢·ÛÌ¿ÙˆÓ (etanercept Î·È adalimumab) Û ·È‰È¿ Ì Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·: 5 ¯ÚfiÓÈ· ÌÂÙ¿ ª. ∆Ú·¯·Ó¿1, ¶. ¶Ú·ÙÛ›‰Ô˘-°Î¤ÚÙÛË1, º. ∫·Ó·ÎÔ‡‰Ë-∆۷ηϛ‰Ô˘1, ∫. ¢È¿Ê·1, °. ¶·Ú‰·Ïfi˜1, ª. ª·ÓÙÔ˘Ú¿ÎË2 ¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ë ·ÔÙ›ÌËÛË Ù˘ 5ÂÙÔ‡˜ ÂÌÂÈÚ›·˜ ·fi ÙË ¯Ú‹ÛË ÙˆÓ ‰‡Ô ·ÚÈˆÓ ·ÓÙÈTNF ·Ú·ÁfiÓÙˆÓ Ô˘ ¯ÔÚËÁÔ‡ÓÙ·È Û ·È‰È¿ Ì ÛÔ‚·Ú¤˜ ÌÔÚʤ˜ Ó·ÓÈ΋˜ ȉÈÔ·ıÔ‡˜ ·ÚıÚ›Ùȉ·˜ (NIA). ÀÏÈÎfi Î·È ª¤ıÔ‰ÔÈ: ªÂÏÂÙ‹ıËÎ·Ó Ë ·ÛÊ¿ÏÂÈ· Î·È Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙˆÓ etanercept (∂∆) Î·È adalimumab (AD) Û 46 ·ÛıÂÓ›˜ Ì ¡π∞, ËÏÈΛ·˜ 2-16 ÂÙÒÓ. √È 32/46 ¤Ï·‚·Ó ET Î·È ÔÈ 14/46 AD, Û˘Á¯ÚfiÓˆ˜ Ì ¤Ó· ÙÚÔÔÔÈËÙÈÎfi Ù˘ ÓfiÛÔ˘ Ê¿ÚÌ·ÎÔ (44/46), ΢ڛˆ˜ ÌÂıÔÙÚÂÍ¿ÙË Î·È Ú‰ÓÈ˙fiÓË (22/46). √È ·ÛıÂÓ›˜ ˘Ô‚¿ÏÏÔÓÙ·Ó ÛÂ Û˘ÛÙËÌ·ÙÈÎfi ÎÏÈÓÈÎfi, ·ÈÌ·ÙÔÏÔÁÈÎfi, ‚ÈÔ¯ËÌÈÎfi, ·ÓÔÛÔÏÔÁÈÎfi Î·È Î·Ú‰ÈÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ÚÈÓ Î·È ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜, ·Ó¿ 6ÌËÓÔ. ∏ ÂÎÙ›ÌËÛË Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ‚·Û›ÛıËΠÛÙ· ÎÚÈÙ‹ÚÈ· «ACR ped 30, 50 Î·È 70». ∞ÔÙÂϤÛÌ·Ù·: ø˜ ÚÔ˜ ÙËÓ ·ÛÊ¿ÏÂÈ·, Û˘Ó‹ıÂȘ ÏÔÈÌÒÍÂȘ ÂÌÊ¿ÓÈÛ·Ó 17/46 ·ÛıÂÓ›˜ (10/32 ˘fi ∂∆ Î·È 3/14 ˘fi AD) Î·È ÛÔ‚·Ú¤˜ ÏÔÈÌÒÍÂȘ 4,7% (1 ˘fi ∂∆, 1 ˘fi AD). ÕÏϘ ÛÔ‚·Ú¤˜ ·ÓÂÈı‡ÌËÙ˜ ·ÓÙȉڿÛÂȘ ‰ÂÓ ·Ú·ÙËÚ‹ıËηÓ. ø˜ ÚÔ˜ ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·, score «ACRped 50-70» ¤Ù˘¯·Ó: ÙÔÓ 1Ô ¯ÚfiÓÔ 88% ÙˆÓ ·ÛıÂÓÒÓ ˘fi ∂∆ Î·È 71% ˘fi AD, ÙÔÓ 2Ô ¯ÚfiÓÔ 81% ˘fi ∂∆ Î·È 66,7% ˘fi AD Î·È ÙÔÓ 3Ô ¯ÚfiÓÔ 83% ˘fi ∂∆ Î·È 100% ˘fi AD. ™ÙË ‰È¿ÚÎÂÈ· Ù˘ 5ÂÙ›·˜, 11/46 ·ÛıÂÓ›˜ (28%) ÌÂÙ·‹‰ËÛ·Ó ·fi ÙÔÓ ¤Ó·Ó ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· ÛÙÔÓ ¿ÏÏÔÓ, 30,5% ‰È¤ÎÔ„·Ó ÏfiÁˆ ‡ÊÂÛ˘ Î·È ¿ÏÏÔÈ 60,8% ·¿ÓÙËÛ·Ó ÈηÓÔÔÈËÙÈο (ACRped 50-70), ÂÓÒ 8,7% ›¯·Ó ÊÙˆ¯‹ ·¿ÓÙËÛË Â›Ù ÛÙÔ ∂∆ ‹ ÛÙÔ AD. ™˘ÌÂÚ¿ÛÌ·Ù·: ∏ ¯ÔÚ‹ÁËÛË ÙˆÓ ·ÓÙÈ-TNF ·Ú·ÁfiÓÙˆÓ Û ·ÓıÂÎÙÈΤ˜ ÛÙË Û˘Ì‚·ÙÈ΋ ıÂڷ›· NIA ·ÔÙÂÏ› ·ÛÊ·Ï‹ Î·È ÈηÓÔÔÈËÙÈ΋ ÂÓ·ÏÏ·ÎÙÈ΋ χÛË. øÛÙfiÛÔ, ·Ú¿ ÙÔ fiÙÈ Ë ÂÌÊ¿ÓÈÛË Ôχ ÛÔ‚·ÚÒÓ ÏÔÈÌÒÍÂˆÓ Â›Ó·È Û¯ÂÙÈο Û¿ÓÈ·, ··ÈÙÂ›Ù·È Û˘ÛÙËÌ·ÙÈ΋ ·ÁÚ‡ÓËÛË ·fi ÙÔ˘˜ ıÂÚ¿ÔÓÙ˜ ÁÈ·ÙÚÔ‡˜ ÁÈ· Ó· ÌËÓ ¤¯Ô˘Ó ÌÔÈÚ·›· ¤Î‚·ÛË.
1 ¶·È‰È·ÙÚÈÎfi ∞ÓÔÛÔÏÔÁÈÎfi Î·È ƒÂ˘Ì·ÙÔÏÔÁÈÎfi ∫¤ÓÙÚÔ ∞Ó·ÊÔÚ¿˜, ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ∞¶£ 2 ¶·È‰Ô·ÎÙÈÓÔÏÔÁÈÎfi ∆Ì‹Ì·, πÔÎÚ¿ÙÂÈÔ °¶¡£ AÏÏËÏÔÁÚ·Ê›·: ª·Ú›· ∆Ú·¯·Ó¿ mtrachan@auth.gr ∫ÏÂÈÔ‡˜ 6 54633 £ÂÛÛ·ÏÔÓ›ÎË
§¤ÍÂȘ ÎÏÂȉȿ: ¡Â·ÓÈ΋ ȉÈÔ·ı‹˜ ·ÚıÚ›Ùȉ·, etanercept, adalimumab, tumor necrosis factor, ıÂڷ›· Ì ·ÓÙÈTNF ·Ú¿ÁÔÓÙ˜.
Administration of two anti-TNF agents (etanercept and adalimumab) in children with juvenile idiopathic arthritis: a 5-year follow-up study M. Trachana1, P. Pratsidou-Gertsi1, F. Kanakoudi-Tsakalidou1, C. Diafa1, G. Pardalos1, M. Bantouraki2 Abstract Background: The aim of this study was to evaluate the 5-year administration of etanercept (ET) or adalimumab (AD) to children with refractory types of juvenile idiopathic arthritis (JIA). Methods: The safety and efficacy of two anti-TNF agents, namely ET and AD, were assessed in 46 children, aged 2-16 years. Of these, 32/46 received ET and 14/46 AD, accompanied by a DMARD (44/46), mainly methotrexate and prednisone (22/46). All the children were assessed by clinical, cardiological, haematological, biochemical and immunologic examination, both pre-treatment and at 6-monthly intervals during treatment. Efficacy was assessed by the application of the ACRped criteria 30, 50, and 70. Results: a) Safety: Common respiratory tract infections were recorded in 17/46 (10/32 on ET and 3/14 on AD). Serious infections were recorded in 2 (4.7%) children (1 on ET, 1 on AD), but no other serious side-effects were observed. b) Efficacy: ACRped 50-70: 1st year: 88% of the ET and 68% of the AD group; 2nd year: 81% of the ET and 71% of the AD group; 3rd year: 83% of the ET and 100% of the AD group. During the 5-year study, 11/46 patients (28%) switched from ET to AD or vice versa, and 30.5% discontinued the anti-TNF treatment due to remission; 60.8% had a satisfactory response to anti-TNF treatment (ACRped 50-70), while 8.7% of patients had a poor response either to ET or to AD.
1 Paediatric Immunology and Rheumatology Referral Center, First Department of Paediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece 2 Outpatient Paediatric Radiology Clinic, “Ippokration” General Hospital, Thessaloniki, Greece Correspondence: Maria Trachana mtrachan@auth.gr 6, Klious St. 54633 Thessaloniki
∏ ·ÚÔ‡Û· ÂÚÁ·Û›· ‚Ú·‚‡ıËΠ̠ÙÔ ∞’ ÈڤÌÂÈÔ µÚ·‚›Ô, ÛÙÔ 46Ô ¶·ÓÂÏÏ‹ÓÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ, ∫¤Ú΢ڷ, 13-15 πÔ˘Ó›Ô˘ 2008 ¶·È‰È·ÙÚÈ΋ 2009;72:29-40
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ª. ∆Ú·¯·Ó¿ Î·È Û˘Ó.
Conclusions: Long-term administration of anti-TNF agents to patients with JIA refractory to the conventional regimen is a safe and alternative solution. Because of the rare appearance of serious infections, systematic vigilance is warranted in order to avoid a possible fatal outcome.
Key words: Juvenile idiopathic arthritis, etanercept, adalimumab, tumor necrosis factor, anti-TNF treatment.
∂ÈÛ·ÁˆÁ‹ H Ó·ÓÈ΋ ȉÈÔ·ı‹˜ ·ÚıÚ›Ùȉ· (¡π∞) Â›Ó·È Ë ÈÔ Û˘¯Ó‹ ÚÂ˘Ì·ÙÈ΋ ¿ıËÛË ÛÙ· ·È‰È¿, Ì ÌÂÁ¿ÏË ÔÈÎÈÏ›· ÎÏÈÓÈ΋˜ ¤ÎÊÚ·Û˘, ÔÚ›·˜ Î·È ¤Î‚·Û˘. √ÚÈṲ̂Ó˜ ÌÔÚʤ˜, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔÓ Ù‡Ô ¤Ó·Ú͢ (Û˘ÛÙËÌ·ÙÈÎfi, ÔÏÈÁÔ·ÚıÚÈÎfi ‹ ÔÏ˘·ÚıÚÈÎfi), ¤¯Ô˘Ó ÔÏ˘·ÚıÚÈ΋ ÔÚ›·, Â›Ó·È ·ÓıÂÎÙÈΤ˜ ÛÙË Û˘Ì‚·ÙÈ΋ ıÂڷ›·, ·ÎfiÌË Î·È ÛÙ· ÈÔ ÂÈıÂÙÈο Û¯‹Ì·Ù·, Î·È Î·Ù·Ï‹ÁÔ˘Ó Û ηٷÛÙÚÔÊÈ΋ ·ÚıÚÔ¿ıÂÈ· Î·È Û ÛÔ‚·Ú‹ ÎÈÓËÙÈ΋ ·Ó·ËÚ›· (1). √È Ì˯·ÓÈÛÌÔ› Ô˘ ÂÌϤÎÔÓÙ·È ¿ÌÂÛ· ‹ ¤ÌÌÂÛ· ÛÙËÓ ·ıÔÁ¤ÓÂÛË Î·È Û˘ÓÙ‹ÚËÛË Ù˘ ¯ÚfiÓÈ·˜ ÊÏÂÁÌÔÓ‹˜ ÙÔ˘ ·ÚıÚÈÎÔ‡ ˘Ì¤Ó· ‰ÂÓ ¤¯Ô˘Ó ·ÎfiÌË ‰È¢ÎÚÈÓÈÛı›, Ê·›ÓÂÙ·È fï˜ fiÙÈ ÔÈ Î˘ÙÙ·ÚÔΛÓ˜ Ô˘ ÚÔ¿ÁÔ˘Ó ÙË ÊÏÂÁÌÔÓ‹ (proinflammatory cytokines IL-1, TNF, IL-6) ηÈ, ΢ڛˆ˜, Ô ·Ú¿ÁÔÓÙ·˜ Ó¤ÎÚˆÛ˘ ÙˆÓ fiÁÎˆÓ (TNF) ·›˙Ô˘Ó ÚˆÙ·ÁˆÓÈÛÙÈÎfi ÚfiÏÔ (2,3). °È· ÙÔ ÏfiÁÔ ·˘ÙfiÓ, ηٿ ÙËÓ ÙÂÏÂ˘Ù·›· 10ÂÙ›· ‰ÔÎÈÌ¿ÛÙËÎ·Ó Ó¤Â˜ ıÂڷ¢ÙÈΤ˜ ÛÙÚ·ÙËÁÈΤ˜ ÛÙ· ·È‰È¿ Ô˘ ¿Û¯Ô˘Ó ·fi ·ÓıÂÎÙÈΤ˜ ÛÙË Û˘Ì‚·ÙÈ΋ ıÂڷ›· ÌÔÚʤ˜ ¡π∞, ÔÈ Ôԛ˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ‚ÈÔÏÔÁÈο ÚÔ˚fiÓÙ· Ô˘ ‰ÚÔ˘Ó ·ÓÙ·ÁˆÓÈÛÙÈο ÚÔ˜ ÙȘ ·Ó·ÊÂÚı›Û˜ ΢ÙÙ·ÚÔΛÓ˜ (4-5). √È ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙÔ˘ TNF-· ‹Ù·Ó ÔÈ ÚÒÙÔÈ ‚ÈÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ô˘ ‰ÔÎÈÌ¿ÛıËÎ·Ó Ì ÂÈÙ˘¯›·, ·Ú¯Èο ÛÙË ÚÂ˘Ì·ÙÔÂȉ‹ ·ÚıÚ›Ùȉ· (ƒ∞) ÙˆÓ ÂÓËÏ›ÎˆÓ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ÛÙË ¡π∞. ™ÙË ¯ÒÚ· Ì·˜ ΢ÎÏÔÊÔÚÔ‡Ó Û‹ÌÂÚ· ÙÚ›· ·ÓÙÈ-TNF Û΢¿ÛÌ·Ù·: ÙÔ etanercept (∂∆, Enbrel©), ÙÔ infliximab (INFL, Remicade©) Î·È ÙÔ adalimumab (AD, Humira©). ∆Ô ∂∆ Â›Ó·È ‰ÈÌÂÚ¤˜ ÌÈ·˜ ¯ÈÌ·ÈÚÈ΋˜ ÚˆÙ½Ó˘ Ô˘ ÚÔ·ÙÂÈ ·fi ÙË Û‡ÓÙËÍË ÙÔ˘ ÂÍˆÎ˘ÙÙ¿ÚÈÔ˘ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ˘Ô‰Ô¯¤·-2 ÙÔ˘ TNF Ì ÙÔ ÙÌ‹Ì· Fc Ù˘ ·ÓıÚÒÈÓ˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ IgG1. ∆Ô Û··ÛÌ· ‰Ú· ˆ˜ ·Ó·ÛÙÔϤ·˜ Ù˘ Û‡Ó‰ÂÛ˘ ÙÔ˘ TNF Ì ÙÔÓ ÂÈÊ·ÓÂÈ·Îfi ΢ÙÙ·ÚÈÎfi ˘Ô‰Ô¯¤· ÙÔ˘ Î·È Û˘ÓÂÒ˜ ·Ó·ÛÙ¤ÏÏÂÈ ÙË ‰Ú¿ÛË ÙÔ˘ (4-6). ∆Ô INFL Â›Ó·È ¤Ó· ¯ÈÌ·ÈÚÈÎfi ÌÔÓÔÎψÓÈÎfi ·ÓÙÈ-TNF ·Óٛۈ̷ Ô˘ ·ÔÙÂÏÂ›Ù·È Î·Ù¿ 25% ·fi IgG1 ÔÓÙÈÎÔ‡ (Fab ÙÌ‹Ì·) Î·È Î·Ù¿ 75% ·fi IgG1 ·ÓıÚÒÔ˘ (Fc ÙÌ‹Ì·). ∆Ô ÚÒPaediatriki 2009;72:29-40
ÙÔ ·ÔÙÂÏ› ÙÔ ÙÌ‹Ì· Û‡Ó‰ÂÛ˘ ÙÔ˘ INFL Ì ÙÔ ‰È·Ï˘Ùfi Î·È ‰È·ÌÂÌ‚Ú·ÓÈÎfi ∆NF-·, ÂÓÒ ÙÔ ‰Â‡ÙÂÚÔ (Fc ÙÌ‹Ì·) ·Ó·ÛÙ¤ÏÏÂÈ ÙȘ ¿ÏϘ ‚ÈÔÏÔÁÈΤ˜ ‰Ú·ÛÙËÚÈfiÙËÙ˜ ÙÔ˘ TNF-· (4-6). ∆Ô adalimumab (AD) Â›Ó·È ÙÔ ÚÒÙÔ ÂÍ ÔÏÔÎÏ‹ÚÔ˘ ·ÓıÚÒÈÓÔ ÌÔÓÔÎψÓÈÎfi ·ÓÙÈTNF ·Óٛۈ̷ Ô˘ ‰ÔÎÈÌ¿ÛÙËΠ·Ú¯Èο ÛÙË ıÂڷ›· Ù˘ ƒ∞ ÙˆÓ ÂÓËϛΈÓ. ªÔÈ¿˙ÂÈ ‰ÔÌÈο Î·È ÏÂÈÙÔ˘ÚÁÈο Ì ÙËÓ ·ÓÔÛÔÛÊ·ÈÚ›ÓË IgG1. ∞Ó·ÛÙ¤ÏÏÂÈ Î·È ·˘Ùfi, fiˆ˜ ÙÔ ∂∆, ÙË Û‡Ó‰ÂÛË ÙÔ˘ TNF Ì ÙÔÓ ÂÈÊ·ÓÂÈ·Îfi ΢ÙÙ·ÚÈÎfi ˘Ô‰Ô¯¤· ÙÔ˘. ∂ÈϤÔÓ, ¤¯ÂÈ ¯·ÌËÏ‹ ·ÓÔÛÔÁÔÓÈÎfiÙËÙ·, ȉÈfiÙËÙ· Ô˘ ÙÔ˘ ÂÈÙÚ¤ÂÈ ÙË Ì·ÎÚÔ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛ‹ ÙÔ˘ ¯ˆÚ›˜ ÙÔ ÂӉ¯fiÌÂÓÔ ÚÒÈÌ˘ ·Ú·ÁˆÁ‹˜ ÂÍÔ˘‰ÂÙÂÚˆÙÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÙÔ˘, ·ÎfiÌË Î·È fiÙ·Ó ‰ÂÓ Ï·Ì‚¿ÓÔÓÙ·È Ù·˘Ùfi¯ÚÔÓ· ·ÓÔÛÔÙÚÔÔÔÈËÙÈο Ê¿Ú̷η, fiˆ˜ Ë ÌÂıÔÙÚÂÍ¿ÙË, ηıÒ˜ Î·È ¯·ÌËÏ‹ Èı·ÓfiÙËÙ· ·ÏÏÂÚÁÈÎÒÓ ·ÓÙȉڿÛÂˆÓ (7). ™Â ÚÔËÁÔ‡ÌÂÓË ÌÂϤÙË Ì·˜ ÂÎÙÈÌ‹ıËÎÂ Ë ·ÛÊ¿ÏÂÈ· Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ‰‡Ô ·ÓÙÈTNF Û΢·ÛÌ¿ÙˆÓ (∂∆ Î·È INFL) Ô˘ ¯ÔÚËÁ‹ıËÎ·Ó ÁÈ· 9 Ì‹Ó˜ Û ÂÈÏÂÁ̤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ·ÓıÂÎÙÈ΋ ÛÙË Û˘Ì‚·ÙÈ΋ ıÂڷ›· ¡π∞, Ë ÔÔ›· ·ÔÙ¤ÏÂÛ ÙËÓ ÚÒÙË Î·Ù·ÁÚ·Ê‹ Ù˘ ·ÛÊ¿ÏÂÈ·˜ Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Ù˘ ·ÓÙÈTNF ıÂڷ›·˜ Û ·È‰È¿ ÛÙË ¯ÒÚ· Ì·˜ (1). ∏ Û˘ÛÛÒÚ¢ÛË Ù˘ ÂÌÂÈÚ›·˜ Ì·˜ ·fi ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙˆÓ ·ÓÙÈ-TNF ·Ú·ÁfiÓÙˆÓ ÛÙË ¡π∞ Ì·˜ Ô‰‹ÁËÛÂ, ·fi ÙÔ 2003 Î·È ÌÂÙ¿, ÛÙËÓ ÂÈÏÔÁ‹ ¯ÚËÛÈÌÔÔ›ËÛ˘ ÌfiÓÔ ÙÔ˘ ET Î·È ÙÔ˘ AD, ÁÈ·Ù› Ì ÙÔ INFL ηٷÁÚ¿ÊËÎ·Ó ·ÊÂÓfi˜ ÌÂÚÈΤ˜ ÂÚÈÙÒÛÂȘ ÛÔ‚·ÚÒÓ ·ÓÂÈı‡ÌËÙˆÓ ·ÓÙȉڿÛÂˆÓ (΢ڛˆ˜ ·Ó·Ê˘Ï·ÎÙÈÎÔ‡ Ù‡Ô˘) Î·È ·ÊÂÙ¤ÚÔ˘ ÌÈ· Êı›ÓÔ˘Û· ÔÚ›· Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ¿˜ ÙÔ˘ (Èı·ÓÒ˜ ÏfiÁˆ ·Ó¿Ù˘Í˘ ÂÍÔ˘‰ÂÙÂÚˆÙÈÎÒÓ ·ÓÙÈۈ̿وÓ), ‹‰Ë ·fi ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ Ù˘ ¯ÔÚ‹ÁËÛ‹˜ ÙÔ˘. ∏ ÙÚ¤¯Ô˘Û· ÌÂϤÙË Û¯Â‰È¿ÛÙËΠ̠ÛÎÔfi Ó· ·ÔÙÈÌ‹ÛÂÈ ÙËÓ 5ÂÙ‹ ÂÌÂÈÚ›· Ì·˜ ·fi ÙË ¯Ú‹ÛË ÙˆÓ ÚÔ·Ó·ÊÂÚı¤ÓÙˆÓ ‰‡Ô ·ÓÙÈ-TNF ·Ú·ÁfiÓÙˆÓ Ô˘ ¯ÚËÛÈÌÔÔÈԇ̠ۋÌÂÚ· Û ·È‰È¿ Ì ÛÔ‚·Ú¤˜ ÌÔÚʤ˜ Ó·ÓÈ΋˜ ȉÈÔ·ıÔ‡˜ ·ÚıÚ›Ùȉ·˜ (NIA) ÛÙÔ Î¤ÓÙÚÔ Ì·˜.
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¶ÂÓÙ·ÂÙ‹˜ ÂÌÂÈÚ›· ·fi ÙË ¯Ú‹ÛË etanercept Î·È adalimumab ÛÙË Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·
¶›Ó·Î·˜ 1. ∫˘ÚÈfiÙÂÚ· ÎÏÈÓÈο ‰Â‰Ô̤ӷ ÙˆÓ 46 ·ÛıÂÓÒÓ Ô˘ ÌÂÏÂÙ‹ıËηÓ
∞Ú¯ÈÎfi˜ ·ÚÈıÌfi˜ ·ÛıÂÓÒÓ º‡ÏÔ (∫/∞) ∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ Ô˘ ÌÂÙ·‹‰ËÛ·Ó ·fi ÙË Ì›· ÔÌ¿‰· ÛÙËÓ ¿ÏÏË* ∞ÚÈıÌfi˜ ·ÓÙÈ-TNF ıÂڷ¢ÙÈÎÒÓ Û˘Ó‰ÚÈÒÓ Ô˘ ηٷÁÚ¿ÊËÎ·Ó ÛÙÔ˘˜ 46 ·ÛıÂÓ›˜ ª¤ÛË ËÏÈΛ· ¤Ó·Ú͢ NIA (Û ¯ÚfiÓÈ·), x(±SD) ª¤ÛË ËÏÈΛ· ¤Ó·Ú͢ ·ÓÙÈ-TNF ıÂڷ›·˜ (Û ¯ÚfiÓÈ·), x(±SD) ∆‡Ô˜ ·ÚıÚ›Ùȉ·˜ ™˘ÛÙËÌ·ÙÈ΋ → ÔÏ˘·ÚıÚ›Ùȉ· ™˘ÛÙËÌ·ÙÈ΋ → Û˘ÛÙËÌ·ÙÈ΋ ¶ÔÏ˘·ÚıÚ›Ùȉ· (RF ıÂÙÈ΋) √ÏÈÁÔ·ÚıÚ›Ùȉ· ÂÂÎÙ·ı›۷ √ÏÈÁÔ·ÚıÚ›Ùȉ· ›ÌÔÓË æˆÚÈ·ÛÈ΋ ∞ÚıÚ›Ùȉ· Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÂÓıÂÛ›Ùȉ· ∞ÛıÂÓ›˜ Ì ˘ÔÙÚÔÈ¿˙Ô˘Û· ÈÚȉÔ΢ÎÏ›Ùȉ· ª¤ÛË ‰È¿ÚÎÂÈ· ÓfiÛÔ˘ ÚÈÓ ÙËÓ ¤Ó·ÚÍË ıÂڷ›·˜ Ì ·ÓÙÈ-TNF - [¤ÙË (‡ÚÔ˜)] ¶ÚÔËÁÔ‡ÌÂÓË ıÂڷ›· ÛÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÓÙÈ-TNF Û˘Ó‰ÚÈÒÓ Ô˘ ¯ÔÚËÁ‹ıËÎ·Ó ÛÙÔ˘˜ 46 ·ÛıÂÓ›˜ (¡=59) ∫·Ì›·† ª∆à CSA ª∆à + CSA ª∆à + ¿ÏÏ· DMARDs‡ CSA + ˘‰ÚÔ͢¯ÏˆÚÔΛÓË INFL INFL + MTX INFL + CSA ∂∆ + MTX ‹ CSA AD + MTX ‹ CSA ¢ÔÛÔÏÔÁÈÎfi Û¯‹Ì· ·ÓÙÈ-TNF ·Ú·ÁfiÓÙˆÓ ¶·Ú¿ÏÏËÏË ıÂڷ›· ÛÙÔ Û‡ÓÔÏÔ ÙˆÓ ıÂڷ¢ÙÈÎÒÓ Û˘Ó‰ÚÈÒÓ Ô˘ ηٷÁÚ¿ÊËÎ·Ó ÛÙÔ˘˜ 46 ·ÛıÂÓ›˜ (¡=59) PDN (ÛÂ Û˘Ó‰˘·ÛÌfi Ì DMARDS Î·È Ì ·ÓÙÈ-TNF)¨ MTX CSA
∂∆
AD
™‡ÓÔÏÔ
32 25/7 4
14 10/4 7
46 35/11 11/46
37 4,84 (±3,59)** 10,69 (±5,38)**
22 4,69 (±3,38)** 12,92 (±4,96)**
59
4 4 16 (4) 6 1 1 0 6
1 0 6 (1) 4 2 0 1 1
5 4 22 (5) 10 3 1 1 7
5,85 (0-16,5)**
8,23 (1,7-19,7)**
2/37 6/37 0/37 16/37 3/37 2/37 0/37 4/37 0/37
0/22 1/22 1/22 11/22 1/22 0/22 1/22 3/22 1/22 7/22
4/37 0,4 mg/kg ‰È˜/‚‰
25 mg/m2/15ËÌ
14/37 31/37 6/37@
11/22 19/22 3/22
2/59 7/59 1/59 27/59 4/59 2/59 1/59 5/59 1/59 7/59 4/59
25/59 50/59 9/59
¶ÔÏ˘- = ÔÏ˘·ÚıÚÈ΋, √ÏÈÁÔ- = ÔÏÈÁÔ·ÚıÚÈ΋, → = ÌÂٿوÛË ÛÂ, ™˘ÛÙËÌ·ÙÈ΋ → Û˘ÛÙËÌ·ÙÈ΋ = Û˘ÛÙËÌ·ÙÈÎfi˜ Ù‡Ô˜ ¤Ó·Ú͢ Î·È ÔÚ›·˜, RF = ÚÂ˘Ì·ÙÔÂȉ‹˜ ·Ú¿ÁÔÓÙ·˜ ∂∆=Etanercept, AD=Adalimumab, PDN=Ú‰ÓÈ˙fiÓË, MTX=ÌÂıÔÙÚÂÍ¿ÙË, CsA=∫˘ÎÏÔÛÔÚ›ÓË ∞ * 2/11 ·ÛıÂÓ›˜ ‹Ú·Ó 2 ÊÔÚ¤˜ ›Ù ∂∆ (1) ›Ù AD (1), ·ÓÙ›ÛÙÔȯ· ** p = NS † ∫·Ó¤Ó· DMARD ÏfiÁˆ ‰˘Û·ÓÔ¯‹˜ ‹ ·ÓÂÈı‡ÌËÙˆÓ ÂÓÂÚÁÂÈÒÓ ‡ √Ì¿‰· ∂∆: ÛÔ˘ÏÊ·Û·Ï·˙›ÓË 1, ˘‰ÚÔ͢¯ÏˆÚÔΛÓË (1), ¿Ï·Ù· ¯Ú˘ÛÔ‡ (1). √Ì¿‰· AD: ˘‰ÚÔ͢¯ÏˆÚÔΛÓË (1) ¨ ¢fiÛË <0.5mg/kg/ËÌ. Ì Êı›ÓÔ˘Û· ÂÏ¿ÙÙˆÛË, Ô˘ ‰ÈÂÎfiË ÌÂÙ¿ ‰È¿ÛÙËÌ· 6-12 ÌËÓÒÓ @ 1 ·ÛıÂÓ‹˜ Û˘Ó¤¯ÈÛ Ì ÏÂÊÏÔ˘ÓÔÌ›‰Ë ÌÂÙ¿ ÙÔÓ 2Ô ¯ÚfiÓÔ, ÏfiÁˆ ·ÓÂÈı‡ÌËÙˆÓ ·ÓÙȉڿÛÂˆÓ ÛÙË CsA
∞ÛıÂÓ›˜ Î·È ª¤ıÔ‰ÔÈ ∞ÛıÂÓ›˜ ªÂÏÂÙ‹ıËÎ·Ó ÚÔÔÙÈο 46 ·ÛıÂÓ›˜ (∫/∞ 34/12), ËÏÈΛ·˜ 2-16 ÂÙÒÓ, Ô˘ ¤·Û¯·Ó ·fi NIA. ∫ÚÈÙ‹ÚÈ· ÂÈÛ·ÁˆÁ‹˜ ÛÙË ÌÂϤÙË: ãŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ›¯·Ó ›ÌÔÓË ÂÓÂÚÁfiÙËÙ· Ù˘ ÓfiÛÔ˘, ·Ú¿ ÙËÓ ÂÈıÂÙÈ΋ Û˘Ì‚·ÙÈ΋ ıÂڷ›· ‹ Î·È ÙË ıÂڷ›· Ì ÙÔÓ ÂÓ‰ÔÊϤ‚È· ¯ÔÚËÁÔ‡ÌÂÓÔ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· (INFL). ∂ȉÈÎfiÙÂÚ·, fiÏÔÈ ÔÈ ·ÛıÂÓ›˜, ÂÎÙfi˜ ·fi 2, ›¯·Ó Ï¿‚ÂÈ ¤Ó· ‹ ÂÚÈÛÛfiÙÂÚ· ÙÚÔÔÔÈËÙÈο Ù˘ ÓfiÛÔ˘ Ê¿Ú̷η (disease modifying antirheumatic
drugs ‹ DMARDs), Ì ‹ ¯ˆÚ›˜ Ú‰ÓÈ˙fiÓË. √È ‰‡Ô ÂÍ·ÈÚÔ‡ÌÂÓÔÈ ·ÛıÂÓ›˜ ›¯·Ó ‰˘Û·ÓÔ¯‹ ÛÙ· DMARDs (¤ÓÙÔÓ˜ Á·ÛÙÚÂÓÙÂÚÈΤ˜ ‰È·Ù·Ú·¯¤˜, ÙÚ·ÓÛ·ÌÈÓ·Û·ÈÌ›· ÛÙË ª∆Ã, ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· ÛÙË CsA) Î·È Â›¯·Ó ‰È·Îfi„ÂÈ ÙËÓ ·ÁˆÁ‹. ∞Ó·Ï˘ÙÈο, ÙÔ Â›‰Ô˜ Ù˘ ÚÔËÁËı›۷˜ ıÂڷ›·˜ ηٷÁÚ¿ÊÂÙ·È ÛÙÔÓ ¶›Ó·Î· 1. ∂ÈÏÔÁ‹ ·ÓÙÈ-∆¡F ·Ú¿ÁÔÓÙ·: ª¤¯ÚÈ ÙÔ 2003 ÙÔ AD ‰ÂÓ Î˘ÎÏÔÊÔÚÔ‡Û ÛÙË ¯ÒÚ· Ì·˜. ãŒÙÛÈ, ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Î·Ù·ÁÚ¿ÊÂÙ·È Ë 4¯ÚÔÓË ÂÌÂÈÚ›· ·fi ÙË ¯ÔÚ‹ÁËÛ‹ ÙÔ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÛÙÔ Î¤ÓÙÚÔ Ì·˜. ¶·È‰È·ÙÚÈ΋ 2009;72:29-40
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·32
32
ª. ∆Ú·¯·Ó¿ Î·È Û˘Ó.
∞Ú¯Èο, ÙÔ AD ·ÔÙ¤ÏÂÛ ÙËÓ ÂÓ·ÏÏ·ÎÙÈ΋ χÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì و¯‹ ·¿ÓÙËÛË ÛÙÔ ∂∆. øÛÙfiÛÔ, ÙËÓ ÙÂÏÂ˘Ù·›· 2ÂÙ›· Ù˘ ÌÂϤÙ˘, ·ÔÙÂÏÔ‡Û ÙËÓ ÚÒÙË ÂÈÏÔÁ‹ Û ·È‰È¿ Ì ¡π∞ Î·È ÈÚȉÔ΢ÎÏ›Ùȉ· (π∫), ÁÈ·Ù› ÂÓÙˆÌÂٷ͇ ÚԤ΢„·Ó ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ Ô˘ ˘ÔÛÙ‹ÚÈ˙·Ó fiÙÈ ÙÔ ∂∆ ‰ÂÓ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË π∫ ηٿ ÙËÓ ÔÚ›· Ù˘ ¡π∞ Î·È ‰ÂÓ ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÔÚ›· Ù˘ ‹‰Ë ÂÁηٷÛÙË̤Ó˘ π∫ (8-10). ¢ËÌÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ: ∆· ΢ÚÈfiÙÂÚ· ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·ÛıÂÓÒÓ ÙˆÓ ‰‡Ô ıÂڷ¢ÙÈÎÒÓ ÔÌ¿‰ˆÓ Û˘ÓÔ„›˙ÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 1 ηÈ, fiˆ˜ Ê·›ÓÂÙ·È, ‰ÂÓ ‰È¤ÊÂÚ·Ó ÛËÌ·ÓÙÈο ÌÂٷ͇ ÙÔ˘˜. √È ·ÛıÂÓ›˜ Ô˘ ÛÙËÓ ÔÚ›· Ù˘ ÌÂϤÙ˘ ›¯·Ó Êı›ÓÔ˘Û· ¤ˆ˜ ÊÙˆ¯‹ ·¿ÓÙËÛË ÌÂÙ·Ë‰Ô‡Û·Ó ·fi ÙË Ì›· ÛÙËÓ ¿ÏÏË ÔÌ¿‰· ıÂڷ›·˜ (.¯. ·fi ∂∆ Û AD ‹ Î·È ·ÓÙ›ÛÙÚÔÊ·), Û˘Ó‹ıˆ˜ Ì›· ‹ ηÈ, Û·ÓÈfiÙÂÚ·, ‰‡Ô ÊÔÚ¤˜. ∂›Û˘, ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰È¤ÎÔÙ·Ó ÙÔÓ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· ÏfiÁˆ ‡ÊÂÛ˘ Î·È ÛÙËÓ ÔÚ›· ˘ÔÙÚÔ›·˙·Ó ¿Ú¯È˙·Ó Í·Ó¿ ıÂڷ›· Ì ÙÔÓ ¿ÏÏÔ ·ÓÙÈ- TNF ·Ú¿ÁÔÓÙ·, ÔfiÙ ηٷٿÛÛÔÓÙ·Ó ÛÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÔÌ¿‰· ıÂڷ›·˜. ãŒÙÛÈ, ÔÈ 46 ·ÛıÂÓ›˜ ¤Ï·‚·Ó Û˘ÓÔÏÈο 57 ıÂڷ›˜. ∞Ó·Ï˘ÙÈο, 4 ·ÛıÂÓ›˜ ÌÂÙ·‹‰ËÛ·Ó ·fi ÙËÓ ÔÌ¿‰· ÙÔ˘ AD ÛÙÔ ∂∆ Î·È 7 ·fi ÙÔ ET ÛÙÔ AD. ¢‡Ô ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ ÔÏ˘·ÚıÚÈ΋ ÌÔÚÊ‹ ‹Ú·Ó ÙÔÓ ›‰ÈÔ ·Ú¿ÁÔÓÙ· 2 ÊÔÚ¤˜ ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘ (∂∆, AD, ET ‹ AD, ∂∆, AD) (¶›Ó·Î·˜ 1). ∂Ù¿ ·ÛıÂÓ›˜ ›¯·Ó ˘ÔÙÚÔÈ¿˙Ô˘Û· π∫ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ Ì ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ Î·È Ë Â›‰Ú·Û‹ ÙÔ˘˜ ÛÙËÓ ÔÚ›· Ù˘ π∫ ÂÎÙÈÌ‹ıËΠ‰È·¯ÚÔÓÈο. ™ÙÔÓ ¶›Ó·Î· 1 ·Ó·Ê¤ÚÂÙ·È ÙÔ ‰ÔÛÔÏÔÁÈÎfi Û¯‹Ì· Ì ÙÔ˘˜ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÊ·ÚÌfiÛıËΠÛÙË ÌÂϤÙË. ∂ȉÈÎfiÙÂÚ·, ÙÔ Û··ÛÌ· ∂∆ ¯ÔÚËÁ‹ıËΠ˘Ô‰fiÚÈ· Û ‰fiÛË 0,4 mg/kg, ‰‡Ô ÊÔÚ¤˜ ‚‰ÔÌ·‰È·›ˆ˜ Î·È ÙÔÓ ÙÂÏÂ˘Ù·›Ô ¯ÚfiÓÔ ÛÙË ‰ÈÏ¿ÛÈ· ‰fiÛË Ì›· ÊÔÚ¿ ÙËÓ Â‚‰ÔÌ¿‰· (n=2). ∆Ô AD ¯ÔÚËÁ‹ıËΠ۠‰fiÛË 25 mg/m2 ·Ó¿ 15‹ÌÂÚÔ Î·È Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ ·Ó¿ ‚‰ÔÌ¿‰· (n=4). √È ÚÒÙ˜ 2-3 ÂÓ¤ÛÂȘ Á›ÓÔÓÙ·Ó ÛÙÔ ¶·È‰ÔÚÂ˘Ì·ÙÔÏÔÁÈÎfi π·ÙÚÂ›Ô Î·È ÔÈ ÁÔÓ›˜ Âηȉ‡ÔÓÙ·Ó ÛÙËÓ ˘Ô‰fiÚÈ· ¯ÔÚ‹ÁËÛË ÙÔ˘ Û΢¿ÛÌ·ÙÔ˜. ™Â ÂÚ›ÙˆÛË ·‰˘Ó·Ì›·˜ ÙÔ˘˜, ÔÈ ˘Ô‰fiÚȘ ÂÓ¤ÛÂȘ Á›ÓÔÓÙ·Ó Ì ¢ı‡ÓË ÙÔ˘ ·È‰È¿ÙÚÔ˘, ÙÔ˘ ÓÔÛÔÎÔÌ›Ԣ ‹ ÙÔ˘ ΤÓÙÚÔ˘ ˘Á›·˜ Ù˘ ÂÚÈÔ¯‹˜ ÙÔ˘ ·ÛıÂÓÔ‡˜, ÌÂÙ¿ ·fi Û˘ÓÂÓÓfiËÛË. ¶·Ú¿ÏÏËÏ· Ì ÙÔ˘˜ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜, fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤·ÈÚÓ·Ó ª∆à ‹ ΢ÎÏÔÛÔÚ›ÓË (CSA) ‹ Î·È Ú‰ÓÈ˙fiÓË (PDN Û ¯·ÌËÏ‹ ‰fiÛË Î·È Û ·Ú‹ÌÂÚÔ Û¯‹Ì·), Ô˘ ‰ÈÂÎfiË ÌÂÙ¿ 6-12 Ì‹Ó˜ (¶›Ó·Î·˜ 1). ª¤ıÔ‰ÔÈ ∏ ÌÂıÔ‰ÔÏÔÁ›· Ù˘ ÚÔÔÙÈ΋˜ ·˘Ù‹˜ ÌÂϤÙ˘ ÂÚÈÏ¿Ì‚·Ó ٷ ÂÍ‹˜: 1. ∂ÎÙ›ÌËÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘ ÚÈÓ ·Ú¯›ÛÂÈ Ë ¯ÔÚ‹ÁËÛË ÙˆÓ ·ÓÙÈ-TNF ·Ú·ÁfiÓÙˆÓ, Ì ‚¿ÛË Ù· ‰ÈÂıÓÒ˜ ·Ô‰ÂÎÙ¿ ÎÚÈÙ‹ÚÈ· ÙˆÓ Giannini Î·È Û˘Ó. (11), Ô˘ ˘ÈÔıÂÙ‹ıËÎ·Ó ·fi ÙÔ ACR (American College of Rheumatologists) Î·È ÔÓoÌ¿˙ÔÓÙ·È Ï¤ÔÓ ACR pediatric criteria (ACRped). ∆· ÎÚÈÙ‹ÚÈ· ·˘Ù¿ ÂÎÙÈÌÔ‡Ó ÙËÓ Î·Ù¿ 30, 50 ‹ 70% ‚ÂÏÙ›ˆÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ (ACRped 30, 50, 70) Î·È ÂÊ·ÚÌfi˙ÔÓÙ·È Û fiϘ ÙȘ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ‰ÈÂıÓÒ˜. ø˜ ÂÏ¿¯ÈÛÙË ‚ÂÏÙ›ˆÛË ıˆÚÂ›Ù·È ÙÔ ACRped 30. √È ÂÚÈÛÛfiÙÂÚÔÈ Û˘ÁÁÚ·Ê›˜, ˆÛÙfiÛÔ, ÚÔÙ›ÓÔ˘Ó ˆ˜ ÈηÓÔÔÈËÙÈ΋ ÙË ‚ÂÏÙ›ˆÛË Î·Ù¿ 50% Î·È ˆ˜ Ôχ ÈηÓÔÔÈËÙÈ΋ ÙË ‚ÂÏÙ›ˆÛË Î·Ù¿ 70% (12). ∆· ÎÚÈÙ‹ÚÈ· ·˘Ù¿ ÂÎÙÈÌÔ‡Ó ÙË ÁÂÓÈ΋ ηٿÛÙ·ÛË Î·È Â˘ÂÍ›· ÙÔ˘ ·ÛıÂÓÔ‡˜, ÙË ÏÂÈÙÔ˘ÚÁÈ΋ ÙÔ˘ ÈηÓfiÙËÙ· Î·È ÙËÓ ÔÈfiÙËÙ· Ù˘ ˙ˆ‹˜ ÙÔ˘ Û ۯ¤ÛË Ì ÙË ¯ÚfiÓÈ· ÓfiÛÔ ÛÙË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Ô˘ Á›ÓÂÙ·È Ë ÂÎÙ›ÌËÛË. ¶ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙȘ ÂÍ‹˜ 6 ˘ÔÎÂÈÌÂÓÈΤ˜ Î·È ·ÓÙÈÎÂÈÌÂÓÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜: 1. ∆Ë ÛÊ·ÈÚÈ΋ ÂÎÙ›Paediatriki 2009;72:29-40
ÌËÛË Ù˘ ÁÂÓÈ΋˜ ηٿÛÙ·Û˘ (‚·Ú‡ÙËÙ· ÓfiÛÔ˘) ÙÔ˘ ·ÛıÂÓÔ‡˜ ·fi ÙÔÓ ıÂÚ¿ÔÓÙ· È·ÙÚfi, Ì ‚·ıÌÔÏfiÁËÛË ÔÙÈ΋˜ ·Ó·ÏÔÁÈ΋˜ Îϛ̷η˜ (VAS) 0-10cm. 2. ∆Ë ÛÊ·ÈÚÈ΋ ÂÎÙ›ÌËÛË Ù˘ ¢ÂÍ›·˜ (well-being) ·fi ÙÔÓ ›‰ÈÔ ÙÔÓ ·ÛıÂÓ‹ ‹ ÙÔ˘˜ ÁÔÓ›˜ ÙÔ˘, Ì ‚·ıÌÔÏfiÁËÛË VAS 0-10cm. 3. ∆Ë ‚·ıÌÔÏfiÁËÛË Ù˘ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÈηÓfiÙËÙ·˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ ·fi ÙÔÓ ›‰ÈÔ ‹ ÙÔ˘˜ ÁÔÓ›˜ ÙÔ˘, Ì ··ÓÙ‹ÛÂȘ Û ÂȉÈÎfi ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ Child Health Assessment Questionnaire (CHAQ). ∞fi ÙÔ CHAQ ÂÍ¿ÁÂÙ·È Ô ¢Â›ÎÙ˘ ªÂÈÔÓÂÎÙÈÎfiÙËÙ·˜ (Disability Index, score 0-3) ÙÔ˘ ·ÛıÂÓÔ‡˜. À¿Ú¯ÂÈ Ë ÂÏÏËÓÈ΋ ¤Î‰ÔÛË ÙÔ˘ CHAQ, Ë ÔÔ›· ¤¯ÂÈ ÂÁÎÚÈı› ·fi ¢ÈÂıÓ›˜ ¶·È‰ÔÚÂ˘Ì·ÙÔÏÔÁÈÎÔ‡˜ √ÚÁ·ÓÈÛÌÔ‡˜ Î·È ¤¯ÂÈ ‰ËÌÔÛÈ¢ı› ÙÔ 2001 (13). ∆Ô CHAQ ÂÊ·ÚÌfi˙ÂÙ·È ·fi 5ÂÙ›·˜ Î·È Ï¤ÔÓ ÛÙÔ Î¤ÓÙÚÔ Ì·˜, ÛÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË Î¿ı ·ÛıÂÓÔ‡˜ Ì ¡π∞. 4. ∆ËÓ ÂÎÙ›ÌËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ·ÚıÚÒÛÂˆÓ Ì ÂÓÂÚÁfi ·ÚıÚ›Ùȉ·. ø˜ ¿ÚıÚˆÛË Ì ÂÓÂÚÁfi ·ÚıÚ›Ùȉ· ÔÚ›˙ÂÙ·È Î¿ı ¿ÚıÚˆÛË Ì ‰ÈfiÁΈÛË Ô˘ ‰ÂÓ ·Ô‰›‰ÂÙ·È Û ÔÛÙÈ΋ ·‡ÍËÛË ‹, Û ·Ô˘Û›· ‰ÈfiÁΈÛ˘, οı ¿ÚıÚˆÛË Ì ÂÚÈÔÚÈṲ̂ÓË ÎÈÓËÙÈÎfiÙËÙ· Ô˘ Û˘Óԉ‡ÂÙ·È Â›Ù ·fi fiÓÔ ÛÙËÓ Î›ÓËÛË Â›Ù ·fi ¢·ÈÛıËÛ›· ÛÙËÓ ÂͤٷÛË. 5. ∆ËÓ ÂÎÙ›ÌËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ·ÚıÚÒÛÂˆÓ Ì ÂÚÈÔÚÈÛÌfi Ù˘ ÎÈÓËÙÈÎfiÙËÙ·˜. 6. ∆ËÓ ÂÎÙ›ÌËÛË Ù˘ ∆∫∂ ‹/Î·È Ù˘ CRP (11). ø˜ ‚ÂÏÙ›ˆÛË Ù˘ ÔÚ›·˜ Ù˘ ÓfiÛÔ˘ ÔÚ›˙ÂÙ·È Ë ‚ÂÏÙ›ˆÛË ≥30% Û ≥3/6 ·Ú·Ì¤ÙÚÔ˘˜, ¯ˆÚ›˜ Ù·˘Ùfi¯ÚÔÓË Âȉ›ӈÛË Û >1 ·Ú·Ì¤ÙÚÔ˘˜ ηٿ >30% (14). ø˜ ˘ÔÙÚÔ‹ ÔÚ›˙ÂÙ·È Ë ·ÚÔ˘Û›· ÔÔÈÔ˘‰‹ÔÙÂ Â˘Ú‹Ì·ÙÔ˜ ÂÓÂÚÁfiÙËÙ·˜ ›Ù ˆ˜ ÚÔ˜ ÙËÓ ·ÚıÚ›Ùȉ· ›Ù ˆ˜ ÚÔ˜ ÙȘ Û˘ÛÙËÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ (14). ø˜ ‡ÊÂÛË ˘fi ıÂڷ›· ÔÚ›ÛÙËÎÂ Ë Î·Ù¿ÛÙ·ÛË Ô˘ ÂÎÏËÚÒÓÂÈ Ù· 5 ÎÚÈÙ‹ÚÈ· ‡ÊÂÛ˘, ÂÓÒ Ô ·ÛıÂÓ‹˜ Â›Ó·È ÁÈ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 6 Û˘Ó¯fiÌÂÓÔ˘˜ Ì‹Ó˜ ˘fi ıÂڷ›·: 1. ·Ô˘Û›· ÂÓÂÚÁÔ‡ ·ÚıÚ›Ùȉ·˜, 2. ·Ô˘Û›· ˘ÚÂÙÔ‡, ÂÍ·Óı‹Ì·ÙÔ˜, ÔÚÔÁÔÓ›Ùȉ·˜, ÌÂÁ·ÏÔÛÏËÓ›·˜ ‹ ÏÂÌÊ·‰ÂÓ›Ùȉ·˜ Ô˘ ·Ô‰›‰ÂÙ·È ÛÙË NIA, 3. ·Ô˘Û›· ÂÓÂÚÁÔ‡ π∫, 4. ·Ô˘Û›· ·˘ÍË̤Ó˘ ∆∫∂ ‹ Î·È CRP Ô˘ ·Ô‰›‰ÂÙ·È ÛÙË NIA, 5. ÛÊ·ÈÚÈ΋ ÂÎÙ›ÌËÛË Ù˘ ‚·Ú‡ÙËÙ·˜ Ù˘ ηٿÛÙ·Û˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ ·fi ÙÔ ıÂÚ¿ÔÓÙ· È·ÙÚfi, Ô˘ ‰ÂÓ ˘Ô‰ÂÈÎÓ‡ÂÈ ÂÓÂÚÁfiÙËÙ· (max 1 cm) (14). 2. ∂ÎÙ›ÌËÛË Ù˘ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘ ÂÚÈÔ‰Èο (1Ô˜, 2Ô˜, 3Ô˜, 6Ô˜ Ì‹Ó·˜ Î·È ·Ó¿ 6 Ì‹Ó˜ ÛÙË Û˘Ó¤¯ÂÈ·), Ì ÙËÓ ÚÔ·Ó·ÊÂÚı›۷ ÌÂıÔ‰ÔÏÔÁ›·. 3. ∂ÎÙ›ÌËÛË Ù˘ ·ÛÊ¿ÏÂÈ·˜ Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜, Ì ‚¿ÛË ÂÚÁ·ÛÙËÚȷο Î·È ÎÏÈÓÈο ‰Â‰Ô̤ӷ: ∂ÎÙfi˜ ·fi ÙËÓ ÂÚÈÔ‰È΋ ÎÏÈÓÈ΋ ÂÎÙ›ÌËÛË, fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ ˘Ô‚¿ÏÏÔÓÙ·Ó Û ÂÚÁ·ÛÙËÚÈ·Îfi, ηډÈÔÏÔÁÈÎfi Î·È ÔÊı·ÏÌÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô Î·È ÂȉÈÎfiÙÂÚ·: ∞. ∞ÈÌ·ÙÔÏÔÁÈÎfi, ‚ÈÔ¯ËÌÈÎfi Î·È ·ÓÔÛÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜, ·Ó¿ Ì‹Ó· ÛÙÔ ÚÒÙÔ 6ÌËÓÔ Î·È ·Ó¿ 6ÌËÓÔ ÌÂÙ¤ÂÈÙ·, fiˆ˜ ¤¯ÂÈ ÂÚÈÁÚ·Ê› ÚÔËÁÔ˘Ì¤Óˆ˜. O ·ÈÌ·ÙÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÚÈÏ¿Ì‚·Ó ÙË ÁÂÓÈ΋ ÂͤٷÛË ÙÔ˘ ·›Ì·ÙÔ˜ Î·È ÙËÓ ∆∫∂, Ô ‚ÈÔ¯ËÌÈÎfi˜ ÙÔÓ ¤ÏÂÁ¯Ô Ù˘ ÓÂÊÚÈ΋˜ Î·È Ë·ÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ (̤ÙÚËÛË ÛÙÔ Ï¿ÛÌ· Ù˘ Ô˘Ú›·˜, ÎÚ·ÙÈÓ›Ó˘, SGPT/SGOT, Á-GT Î·È ÁÂÓÈ΋ ÂͤٷÛË Ô‡ÚˆÓ), ηıÒ˜ Î·È ÙË Ì¤ÙÚËÛË Ù˘ ÁÏ˘Îfi˙˘ Ï¿ÛÌ·ÙÔ˜. √ ·ÓÔÛÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÚÈÏ¿Ì‚·Ó ÙË Ì¤ÙÚËÛË Ì ÙȘ ηıÈÂڈ̤Ó˜ Ù¯ÓÈΤ˜ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ·ÓÔÛÔÛÊ·ÈÚÈÓÒÓ (IgA, IgM, IgG IgE) Î·È ÙˆÓ ˘ÔÙ¿ÍÂˆÓ Ù˘ IgG, ÙˆÓ ÎÏ·ÛÌ¿ÙˆÓ Ùo˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ C3,C4, ÙÔ˘ ÚÂ˘Ì·ÙÔÂȉԇ˜ ·Ú¿ÁÔÓÙ· (RF) Î·È ÙËÓ ·Ó›¯Ó¢ÛË Î·È ÙÔÓ Ù›ÙÏÔ ‰È·ÊfiÚˆÓ ·˘ÙÔ·ÓÙÈۈ̿وÓ: ·ÓÙÈ˘ÚËÓÈο (∞¡∞), ·ÓÙÈ-DNA, ηٿ Âί˘ÏÈÛÌ¿ÙˆÓ ÙÔ˘ ˘Ú‹Ó· (·ÓÙÈ-∂¡∞) Î·È ÂȉÈÎfiÙÂÚ· Ù· ·ÓÙÈ-SSA ‹ Ro, ·ÓÙÈ-SSB ‹ La, ·ÓÙÈ-Sm, ·ÓÙÈ-URNP, ·ÓÙÈ-Jo, ·ÓÙÈ-Scl70, ·ÓÙÈ-Cenp-B,
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·33
33
¶ÂÓÙ·ÂÙ‹˜ ÂÌÂÈÚ›· ·fi ÙË ¯Ú‹ÛË etanercept Î·È adalimumab ÛÙË Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·
¶›Ó·Î·˜ 2. ∞ÓÂÈı‡ÌËÙ· Û˘Ì‚¿Ì·Ù· ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜ (59 ·ÓÙÈ-TNF Û˘Ó‰ڛ˜) ∂›‰Ô˜ ·ÓÂÈı‡ÌËÙ˘ ·ÓÙ›‰Ú·Û˘ ™˘¯Ó¤˜ ÏÔÈÌÒÍÂȘ Ô˘ÚÔÔÈËÙÈÎÔ‡ ™˘¯Ó¤˜ ÏÔÈÌÒÍÂȘ ·Ó·Ó¢ÛÙÈÎÔ‡ ŒÚ˘ ˙ˆÛÙ‹Ú·˜ (·Ú·ÙÂٷ̤ÓË ÔÚ›·) ∂Ú‡ıËÌ· Î·È ÎÓËÛÌfi˜ ÛÙÔ ÛËÌÂ›Ô Ù˘ ¤ÓÂÛ˘ (ÙÔÈ΋ ·ÓÙ›‰Ú·ÛË) ∫Ó›‰ˆÛË, ·ÚıÚ·ÏÁ›Â˜ ÌÂÙ¿ ÙËÓ ¤ÓÂÛË (Û˘ÛÙËÌ·ÙÈ΋ ·ÓÙ›‰Ú·ÛË) ∆ÚȯfiÙˆÛË ∂̇ÚÂÙÔ ÌË Î·ıÔÚÈÛı›۷˜ ·ÈÙÈÔÏÔÁ›·˜ Î·È ı¿Ó·ÙÔ˜ ÂÓÙfi˜ ‚‰ÔÌ¿‰·˜* (·Ô‰fiıËΠ۠Ôχ ÛÔ‚·Ú‹ Ïԛ̈ÍË)
∂∆ (n=37)
AD (n=22)
™‡ÓÔÏÔ (n=59)
1 10 1 0 0 0
0 7 0 1 2 1
1 17 1 1 2 1
0*
1*
1
* 2 Ì‹Ó˜ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË ÙÔ˘ AD Î·È ÌÂÙ¿ ·fi ÚÔËÁËı›۷ ‰ÈÂÙ‹ ıÂڷ›· Ì AD Î·È 9ÌËÓË ıÂڷ›· Ì ∂∆ (‚Ϥ Î›ÌÂÓÔ)
·ÓÙÈ-ÚÈ‚Ôۈ̷ÙÈο Î·È ·ÓÙÈ-ÈÛÙfiÓ˜. ∂›Û˘, ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ηٿ ÙÔ˘ ΢ÙÙ·ÚÔÏ¿ÛÌ·ÙÔ˜ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ (cANCA Î·È p-ANCA) Î·È ·ÓÙÈηډÈÔÏÈȉÈο (Acl). µ. ∫·Ú‰ÈÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ Î·È ·Ó¿ 6ÌËÓÔ ÌÂÙ¤ÂÈÙ·. √ ηډÈÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÚÈÏ¿Ì‚·Ó ËÏÂÎÙÚÔηډÈÔÁÚ¿ÊËÌ·, ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ηډȿ˜ 2 ‰È·ÛÙ¿ÛÂˆÓ Î·È Doppler. °. √Êı·ÏÌÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô (Û¯ÈÛÌÔÂȉ‹˜ Ï˘¯Ó›·, ‚˘ıÔÛÎfiËÛË) ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ Î·È ·Ó¿ 4ÌËÓÔ ÌÂÙ¤ÂÈÙ·. ¢. ∫·Ù·ÁÚ·Ê‹ ·fi ÙÔ˘˜ ÁÔÓ›˜, Û ÚÔۯ‰ȷṲ̂ÓÔ ËÌÂÚÔÏfiÁÈÔ, fiÏˆÓ ÙˆÓ ·ÓÂÈı‡ÌËÙˆÓ ·ÓÙȉڿÛÂˆÓ Ô˘ ›¯·Ó Û¯¤ÛË Ì ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· (ÙÔÈΤ˜ Î·È Û˘ÛÙËÌ·ÙÈΤ˜ ·ÓÙȉڿÛÂȘ), ηıÒ˜ Î·È Î·Ù·ÁÚ·Ê‹ οı ÌÂÙ·‚ÔÏ‹˜ Ù˘ ÁÂÓÈ΋˜ ηٿÛÙ·Û˘ ÙÔ˘ ·È‰ÈÔ‡ ÙÔ˘˜ Î·È Î¿ıÂ Â˘Ú‹Ì·ÙÔ˜ ÂÓ‰ÂÈÎÙÈÎÔ‡ Âȉ›ӈÛ˘ Ù˘ ˘ÔΛÌÂÓ˘ ÓfiÛÔ˘ ‹ Ó¤·˜ ÓfiÛÔ˘ (.¯. Ïԛ̈͢ Ô˘ Û˘Ó¤‚Ë ÛÙÔ ÌÂÛԉȿÛÙËÌ· ÌÂٷ͇ ‰‡Ô ÂÈÛΤ„ˆÓ). ™Ù·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË: ∫·Ù·ÁÚ¿ÊËÎ·Ó fiϘ ÔÈ ·Ú¿ÌÂÙÚÔÈ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙ· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ACRped, ÛÙËÓ ¤Ó·ÚÍË ıÂڷ›·˜ Î·È ÛÙËÓ ÔÚ›· Û ÂÙ‹ÛÈ· ‚¿ÛË. ø˜ ÈηÓÔÔÈËÙÈ΋ ·¿ÓÙËÛË ÔÚ›ÛÙËÎÂ Ë ACRped 50, ¿ÚÈÛÙË Ë ACRped 70 ÂÓÒ ÔÚȷ΋ Ë ACRped 30 Î·È Ùˆ¯‹ Ë ACRped<30. ∏ ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ¤ÁÈÓ ۇÌʈӷ Ì ÙËÓ ÚÔÙÂÈÓfiÌÂÓË ·fi ÙÔ˘˜ Lovell Î·È Û˘Ó. Î·È Lahdenne Î·È Û˘Ó. ÌÂıÔ‰ÔÏÔÁ›· (12,15). ÀÔÏÔÁ›ÛÙËÎÂ Ë Ì¤ÛË ÙÈÌ‹ (mean) Ù˘ οı ·Ú·Ì¤ÙÚÔ˘, Ë ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË (SD) Î·È Ë ‰È¿ÌÂÛË ÙÈÌ‹ (median) ÛÙË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Ù˘ ÂÎÙ›ÌËÛ˘, Ì ÏÔÁÈÛÌÈÎfi ÚfiÁÚ·ÌÌ· (STATISTICA) Î·È Ë % ‚ÂÏÙ›ˆÛ‹ Ù˘ Û˘ÁÎÚÈÙÈο Ì ÙËÓ ÙÈÌ‹ ÛÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘.
∞ÔÙÂϤÛÌ·Ù· ∞fi ÙÔ˘˜ 46 ·ÛıÂÓ›˜, 8 ˘fi ∂∆ Û˘ÌÏ‹ÚˆÛ·Ó 5 ¯ÚfiÓÈ· ıÂڷ›·˜ Î·È ÔÈ 2 ˘fi AD ‚Ú›ÛÎÔÓÙ·È ÛÙÔÓ 5Ô ¯ÚfiÓÔ ıÂڷ›·˜, ÂÓÒ 50% ·fi ÙËÓ Î¿ı ÔÌ¿‰· (¡=18 Î·È ¡=10 ·ÓÙ›ÛÙÔȯ·) Û˘ÌÏ‹ÚˆÛ·Ó ‹‰Ë 3 ¯ÚfiÓÈ· ıÂڷ›·˜. ∞ÛÊ¿ÏÂÈ· ∫·È ÔÈ 2 ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ ·Ô‰Â›¯ıËÎ·Ó ·ÛÊ·Ï›˜ ÁÈ· ÙËÓ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ (¶›Ó·Î·˜ 2). ã∏Ș ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ: ™Â 17/46 ·ÛıÂ-
Ó›˜ ÛËÌÂÈÒıËÎ·Ó Û˘¯Ó¤˜, ÎÔÈÓ¤˜ ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ (17) ‹/Î·È ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡ (1). ◊Ș, ÙÔÈΤ˜ ·ÏÏÂÚÁÈΤ˜ ·ÓÙȉڿÛÂȘ ÛÙÔ ÛËÌÂ›Ô Ù˘ ¤ÓÂÛ˘ ÛËÌÂÈÒıËÎ·Ó Û ¤Ó·Ó ·ÛıÂÓ‹ (AD), Û˘ÛÙËÌ·ÙÈΤ˜ ·ÏÏÂÚÁÈΤ˜ ·ÓÙȉڿÛÂȘ Û 2 (AD) Î·È ÙÚȯfiÙˆÛË Û ¤Ó·Ó ¿ÏÏÔ (AD). ™Ô‚·Ú¤˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ: ŒÓ·˜ ·ÛıÂÓ‹˜ (∂∆) ·ÚÔ˘Û›·Û ¤ÚËÙ· ˙ˆÛÙ‹Ú· Ì ·Ú·ÙÂٷ̤ÓË ÔÚ›· Î·È ¯ÚÂÈ¿ÛıËΠ·ÁˆÁ‹ Ì ·Î˘ÎÏÔ‚›ÚË. ∆¤ÏÔ˜, Ì›· ¿ÏÏË ·ÛıÂÓ‹˜ η٤ÏËÍÂ, 2 Ì‹Ó˜ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘ AD Î·È ·ÊÔ‡ ›¯Â ÚÔËÁËı› ‰ÈÂÙ‹˜ ıÂڷ›· ¿ÏÈ Ì AD Î·È ÛÙË Û˘Ó¤¯ÂÈ· 9ÌËÓË ıÂڷ›· Ì ∂∆. ∏ ·ÛıÂÓ‹˜ ·˘Ù‹ ·ÚÔ˘Û›·Û Â̇ÚÂÙÔ ÌË Î·ıÔÚÈÛı›Û˘ ·ÈÙÈÔÏÔÁ›·˜ Î·È Î·Ù¤ÏËÍ ¤Ó· 24ˆÚÔ ÌÂÙ¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ Ù˘ Û ÓÔÛÔÎÔÌÂ›Ô Ù˘ ÂÚÈʤÚÂÈ·˜, Ì Èı·Ó‹ ‰È¿ÁÓˆÛË «Ïԛ̈ÍË ÙÔ˘ ∫¡™». ∏ ·ÛıÂÓ‹˜ ‹Ù·Ó ¯·ÌËÏÔ‡ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎÔ‡ ÂȤ‰Ô˘, ›¯Â Ù·Íȉ¤„ÂÈ ÚÔËÁÔ˘Ì¤Óˆ˜ Û ¿ÏÏË, ·Ó·Ù˘ÛÛfiÌÂÓË ¯ÒÚ·, fiÔ˘ Î·È ÍÂΛÓËÛ·Ó Ù· Û˘ÌÙÒÌ·Ù· (˘ÚÂÙfi˜, ÎÂÊ·Ï·ÏÁ›·, ·ÓÔÚÂÍ›· Î·È ÓˆıÚfiÙËÙ·), Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌÂÛÔÏ·‚‹ÛÂÈ ÛËÌ·ÓÙÈ΋ ηı˘ÛÙ¤ÚËÛË ÚÔÛ¤Ï¢Û˘ Û ÂÏÏËÓÈÎfi ÓÔÛÔÎÔÌ›Ô, ÛÙÔ ÔÔ›Ô Î·È ¤ÁÈÓ ÂÈÛ·ÁˆÁ‹ Û ÙÂÏÈÎfi ÛÙ¿‰ÈÔ Ù˘ ÓfiÛÔ˘ Ì ·ÓÔ˘Ú›·. ¢˘ÛÙ˘¯Ò˜, ‰ÂÓ ¤ÁÈÓ ÓÂÎÚÔÙÔÌ‹. ∆· ·ÔÙÂϤÛÌ·Ù· ˆ˜ ÚÔ˜ ÙËÓ ÂÌÊ¿ÓÈÛË Ó¤ˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ ·ÔÙ¤ÏÂÛ·Ó ·ÓÙÈΛÌÂÓÔ ÚÔËÁÔ‡ÌÂÓ˘ ÌÂϤÙ˘ (16). ∂ÎÙ›ÌËÛË Ù˘ ›‰Ú·Û˘ Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜ ÛÙËÓ ÔÚ›· Ù˘ ÈÚȉÔ΢ÎÏ›Ùȉ·˜: ¢‡Ô ·ÛıÂÓ›˜, ·ÚÔ˘Û›·Û·Ó ›ÌÔÓË π∫ ÁÈ· ÚÒÙË ÊÔÚ¿ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ NIA, 10 Î·È 15 ¯ÚfiÓÈ· ·ÚÁfiÙÂÚ· Î·È ÂÓÒ ‹Ù·Ó Û ·ÓÙÈ-TNF ıÂڷ›· Ì ∂∆. ∏ π∫ ‹Ù·Ó ·ÓıÂÎÙÈ΋ ÙfiÛÔ ÛÙËÓ ÙÔÈ΋ ıÂڷ›· fiÛÔ Î·È ÛÙËÓ ·ÓÙÈTNF, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·ÎÔ‹ ÙÔ˘ ∂∆ Î·È ÙË ¯ÔÚ‹ÁËÛË AD. ∏ π∫ ˘Ô¯ÒÚËÛÂ Î·È ‰ÂÓ ˘ÔÙÚÔ›·Û Û fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜ Ì AD. ™Â ¿ÏÏÔ˘˜ 4 ·ÛıÂÓ›˜ Ì ¡π∞ Î·È ÈÛÙÔÚÈÎfi ˘ÔÙÚÔÈ¿˙Ô˘Û·˜ π∫, ÙÔ ∂∆ ‰ÂÓ Ê¿ÓËΠӷ ÂËÚ¤·Û ÙËÓ ÂÓÂÚÁfiÙËÙ· ¶·È‰È·ÙÚÈ΋ 2009;72:29-40
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·34
34
¶ÔÛÔÛÙfi ·ÛıÂÓÒÓ
-6,5±2,1 -85,7±20,2 -6,5 -85,7 -66,6±40,5 -82,1
N=36
N=32
N=18
N=10
N=8
80% ACR <30 ACR 30 ACR 50 ACR 70
60% 40% 20% 0%
1
2 3 4 ÃÚfiÓÈ· ıÂڷ›·˜
5
∂ÈÎfiÓ· 1. ∂Ù‹ÛÈ· ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ Etanercept Û‡Ìʈӷ Ì ٷ ÎÚÈÙ‹ÚÈ· ACRped.
Ù˘ π∫. ™Â 2/4 Ë π∫ ÂϤÁ¯ıËΠÌÂÙ¿ ·fi Ì·ÎÚÔ¯ÚfiÓÈ· ÙÔÈ΋ ıÂڷ›· Î·È ÛÙÔ˘˜ ¿ÏÏÔ˘˜ 2 Ì ÙËÓ ·ÏÏ·Á‹ Ù˘ ıÂڷ›·˜ ·fi ∂∆ Û AD (¶›Ó·Î·˜ 1). ∂ÈϤÔÓ, Û 1 ·ÛıÂÓ‹ Ì ¡π∞ Î·È ÈÛÙÔÚÈÎfi ˘ÔÙÚÔÈ¿˙Ô˘Û·˜ π∫, Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ AD ›¯Â ·Ú¯Èο ÁÈ· 2 ¯ÚfiÓÈ· ¢ÓÔ˚΋ ›‰Ú·ÛË ÛÙËÓ ÔÚ›· Ù˘ π∫, ·ÏÏ¿ ÛÙË Û˘Ó¤¯ÂÈ· Ë π∫ ˘ÔÙÚÔ›·ÛÂ.
* ·: ª¤ÛË ÌÂÙ·‚ÔÏ‹ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜, ‚: % ÌÂÙ·‚ÔÏ‹ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜
-71,4±39,3 -94,3 -4±2,9 -5 -66,8±45,7 -89,4 -72,3±43,4 -92,8
-3,3±2,7 -3,8 -3,1±2,6 -3 4±2,6 3,6
Paediatriki 2009;72:29-40
100%
-3,8±2,7 -4
-0,2±0,3 -61,6±42,8 -0,1 -60 -4±3,2 -75,2±45,6 -3,8 -95 -32,7±77,5 -50 -63,8±33,3 -68,8 -74,3±39,1 -100 -81,3±24,5 -92,9 -0,6±0,6 -0,5 -3,8±2,5 -3,5 -52,1±77,5 -9 -82,2±23,9 -88,9 -0,6±0,7 0,5 -3,5±2,2 -3 0,8±0,7 0,6 4,4±2,3 4
-67,6±49,6 -100 -77,7±34,2 -91,5
-0,7±0,7 -0,5 -4,3±2,4 -4
-0,7±1,1 -0,4 -3,5±2,6 -3,2
-59,2±77,1 -100 -66,2±47,4 -92,9 -49,5±81 -92,8 -46,8±33,6 -55,5 -42,7±72,8 -80,2 -64,5±64 -3,9±2,2 -100 -5 -65,1±62,5 -11±12,4 -91,2 -7 -59±60,2 -6,3±4,3 -79,2 -7 -49,3±44,8 -31,6±24 -60 -35,5 -80,2±24,8 -45,8±31,6 -92,8 -58 -77,2±37,6 -100 -84,2±29 -100 -80,5±29,8 -100 -49,5±61,4 -72,7 -76,5±43,9 -91,6 -4,8±8,5 -3 -9,1±10,7 -5 -7,4±5,1 -5,5 -33,7±29,2 -31 -44,9±43,3 -40 6±9 -4,8±7,5 -72,3±40 4 -3 -100 10,5±12,3 -8,5±10,3 -75,7±35 6 -5 -100 9,7±9 -7,4±6,05 -80,2±25,7 6 -5 -93,8 46,2±26,3 -24,8±25,3 -42,2±58 44 -25 -62,2 42,7±42,3 -34,6±43,8 -65,8±52,9 40 -26 -95
∞Ú. ‰ÈÔÁÎˆÌ¤ÓˆÓ ·ÚıÚÒÛÂˆÓ (x± SD, median) ∞Ú. ÂÒ‰˘ÓˆÓ ·ÚıÚÒÛÂˆÓ (x±SD, median) ∞Ú. ·ÚıÚÒÛÂˆÓ Ì ÂÓÂÚÁfi ÓfiÛÔ (x±SD, median) ∆∫∂ (x± SD, median) CRP (x± SD, median) ¢Â›ÎÙ˘ ªÂÈÔÓÂÎÙÈÎfiÙËÙ·˜ (CHAQ) (0-3) (x±SD, median) ™Ê·ÈÚ. ∂ÎÙ›ÌËÛË π·ÙÚÔ‡ (0-10) (x±SD, median) ™Ê·ÈÚ. ∂ÎÙ›ÌËÛË ∂˘ÂÍ›·˜ ·fi ÙÔ˘˜ ÁÔÓ›˜ (0-10) (x±SD, median)
·
-60±52,3 -92,9 -76,4±36 -97,2 -80,1±30,2 -96,4 -45,5±40,8 -70,4 -59,1±95,1 -94,6
-5±5,6 -4 -9,5±9,5 -7 -7,8±5 -6,5 -41,9±30,1 -40 -49,7±30,2 -51
-6,4±8,8 -5 -11,8±11 -7,5 -6,9±4,5 -5,5 -32,7±24,8 -35,5 -57,3±48,4 -50
‚ (%) 4 (N=10) · ‚ (%) ·
ÃÚfiÓÔ˜ 3 (N=18) 2 (N=32) ‚ (%) 1 (N=37) ·* ‚ (%) ŒÓ·ÚÍË ıÂڷ›·˜
¶›Ó·Î·˜ 3. ∂Ù‹ÛÈ· ÂÎÙ›ÌËÛË Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ÙÔ˘ Etanercept, Ì ‚¿ÛË Ù· ÎÚÈÙ‹ÚÈ· ACRped ÛÙÔ˘˜ 36 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘. ™‡ÓÔÏÔ ıÂڷ¢ÙÈÎÒÓ Û˘Ó‰ÚÈÒÓ: 37
·
5 (N=8) ‚ (%)
ª. ∆Ú·¯·Ó¿ Î·È Û˘Ó.
∞ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ™ÙÔ˘˜ ¶›Ó·Î˜ 3 Î·È 4 ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ë ÌÂÙ·‚ÔÏ‹ ÛÙȘ ÂÈ̤ÚÔ˘˜ ·Ú·Ì¤ÙÚÔ˘˜ Ô˘ ÌÂÏÂÙ‹ıËÎ·Ó ÁÈ· ÙËÓ ÂÎÙ›ÌËÛË Ù˘ ‚ÂÏÙ›ˆÛ˘ Ù˘ ÓfiÛÔ˘ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ 59 ıÂڷ¢ÙÈÎÒÓ Û˘Ó‰ÚÈÒÓ Ì ٷ ‰‡Ô Û΢¿ÛÌ·Ù·, ∂∆ (¶›Ó·Î·˜ 3) Î·È AD (¶›Ó·Î·˜ 4), ÂÓÒ ÛÙÔÓ ¶›Ó·Î· 5 Î·È ÛÙȘ ∂ÈÎfiÓ˜ 1 Î·È 2 ηٷÁÚ¿ÊÂÙ·È Ë ·Ó¿ ¤ÙÔ˜ ÂÎÙ›ÌËÛË Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ÙˆÓ ‰‡Ô ·˘ÙÒÓ Û΢·ÛÌ¿ÙˆÓ, Ì ٷ ACRped ÎÚÈÙ‹ÚÈ·, ÛÙÔ˘˜ 46 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘. ∞fi ÙËÓ ·Ó¿Ï˘ÛË ÙÔ˘ ¶›Ó·Î· 5 ÚÔ·ÙÔ˘Ó Ù· ÂÍ‹˜: √Ì¿‰· ∂∆: ™ÙÔÓ 1Ô ¯ÚfiÓÔ ıÂڷ›·˜ ÙˆÓ ·ÛıÂÓÒÓ, 88,88% ¤Ù˘¯·Ó ÛËÌ·ÓÙÈ΋ ‚ÂÏÙ›ˆÛË Ù˘ ÓfiÛÔ˘ (ACRped 50-70) Î·È Î·Ó¤Ó·˜ ‰ÂÓ ˘ÔÙÚÔ›·ÛÂ. ∆ÔÓ 2Ô ¯ÚfiÓÔ ıÂڷ›·˜, 81,25% ÙˆÓ ·ÛıÂÓÒÓ ¤Ù˘¯·Ó ÛËÌ·ÓÙÈ΋ ‚ÂÏÙ›ˆÛË (ACRped 50-70), 7 ·ÛıÂÓ›˜ ‰È¤ÎÔ„·Ó ÙË ıÂڷ›·, Ô ¤Ó·˜ ÏfiÁˆ ˘ÔÙÚÔ‹˜, ¤Ó·˜ ¿ÏÏÔ˜ ÏfiÁˆ ·Ó¿Ù˘Í˘ π∫, (15 ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ NIA) Î·È ¿ÏÏÔÈ 5 ÏfiÁˆ Ï‹ÚÔ˘˜ ‡ÊÂÛ˘ Ù˘ ÓfiÛÔ˘. ∆ÔÓ 3Ô ¯ÚfiÓÔ ıÂڷ›·˜, 83,33% ÙˆÓ ·ÛıÂÓÒÓ ¤Ù˘¯·Ó ÛËÌ·ÓÙÈ΋ ‚ÂÏÙ›ˆÛË (ACRped 50-70). ∆ÚÂȘ ·ÛıÂÓ›˜ ‰È¤ÎÔ„·Ó ÏfiÁˆ Ï‹ÚÔ˘˜ ‡ÊÂÛ˘ Ù˘ ÓfiÛÔ˘ Î·È Î·Ó¤Ó·˜ ‰ÂÓ ·ÚÔ˘Û›·Û ˘ÔÙÚÔ‹. ∆ÔÓ 4Ô ¯ÚfiÓÔ ıÂڷ›·˜, 80% ÙˆÓ ·ÛıÂÓÒÓ ¤Ù˘¯·Ó ACRped 50-70, 2 ·ÛıÂÓ›˜ ‰È¤ÎÔ„·Ó ÏfiÁˆ ‡ÊÂÛ˘ Ù˘ ÓfiÛÔ˘ Î·È Î·Ó¤Ó·˜ ‰ÂÓ ˘ÔÙÚÔ›·ÛÂ. ∆¤ÏÔ˜, ÙÔÓ 5Ô ¯ÚfiÓÔ ıÂڷ›·˜, ACRped 50-70 ¤Ù˘¯·Ó 75% ÙˆÓ ·ÛıÂÓÒÓ Î·È 2 ·ÛıÂÓ›˜ ‰È¤ÎÔ„·Ó ÙË ıÂڷ›· ›Ù ÏfiÁˆ ‡ÊÂÛ˘ (1) ›Ù ÏfiÁˆ ÂÌÊ¿ÓÈÛ˘ π∫ (1), ÂÓÒ Ô ›‰ÈÔ˜ ¤Ù˘¯Â ACRped 70 ˆ˜ ÚÔ˜ ÙËÓ ·ÚıÚ›Ùȉ·.
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·35
35
-93,2±15 -100 -92,8±16 -100 -89,3±14,4 -100 -40,6±58,7 -64,7 75,6±548,1 -98,7 -73,1±39,8 -92,5 -87,3±15,5 -88,1 -87,3±15,5 -93,9 * ·: ª¤ÛË ÌÂÙ·‚ÔÏ‹ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜, ‚: % ÌÂÙ·‚ÔÏ‹ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜ ** √È ·ÛıÂÓ›˜ Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÙÔÓ 5Ô ¯ÚfiÓÔ ıÂڷ›·˜ ·ÏÏ¿ ‰ÂÓ ÙÔÓ Û˘ÌÏ‹ÚˆÛ·Ó ·ÎfiÌË ‰ÂÓ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔÓ ›Ó·Î·
-3,7±0,6 -4 -9,1±9,1 -6,5 -9±9,7 -5 -23,9±25,5 -22 -49,9±55,8 -38,5 -0,5±0,4 -0,5 -3,2±1,6 -2,2 -3,2±1,5 -3
√Ì¿‰· AD: ¶·ÚfiÌÔÈ· ‹Ù·Ó Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÔÌ¿‰·˜ ÙÔ˘ AD. ∆ÔÓ 1Ô ¯ÚfiÓÔ ıÂڷ›·˜, ACRped 50-70 ¤Ù˘¯·Ó 71,42% ÙˆÓ ·ÛıÂÓÒÓ, ÂÓÒ 3 ·ÛıÂÓ›˜ ‰È¤ÎÔ„·Ó ÙË ıÂڷ›· ÏfiÁˆ ˘ÔÙÚÔ‹˜ Ù˘ ÓfiÛÔ˘. ∫·È ÔÈ 3 ›¯·Ó ÔÏ˘·ÚıÚ›Ùȉ· (1/3 RF ıÂÙÈÎfi˜) Î·È ÔÈ 2/3 ›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ ÚÔËÁÔ˘Ì¤Óˆ˜ ¿ÏÏÔ˘˜ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ › 2 ¯ÚfiÓÈ·, INFL (1) Î·È ∂∆ (1). ∆ÔÓ 2Ô ¯ÚfiÓÔ ıÂڷ›·˜, ACRped 50-70 ¤Ù˘¯·Ó 66,7% ÙˆÓ ·ÛıÂÓÒÓ Î·È 3 ‰È¤ÎÔ„·Ó ÏfiÁˆ ˘ÔÙÚÔ‹˜ Ù˘ ÓfiÛÔ˘. ∫·È ÔÈ 3 ›¯·Ó ÔÏ˘·ÚıÚ›Ùȉ· (3/3 RF ·ÚÓËÙÈÎfi˜) Î·È ÔÈ 2/3 ›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ ÚÔËÁÔ˘Ì¤Óˆ˜ ¿ÏÏÔ˘˜ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ › 2 ¯ÚfiÓÈ·, INFL (1) Î·È ∂∆ (1). ™ÙÔÓ 3Ô ¯ÚfiÓÔ ıÂڷ›·˜, fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ (100%) ¤Ù˘¯·Ó ACRped 50-70 Î·È 1 ‰È¤ÎÔ„Â ÙË ıÂڷ›· ÏfiÁˆ ‡ÊÂÛ˘ Ù˘ ÓfiÛÔ˘. √ ·ÛıÂÓ‹˜ ·˘Ùfi˜ ›¯Â ·Ú¯›ÛÂÈ Ì ∂∆ Î·È ÙÔ Â›¯Â ‰È·Îfi„ÂÈ ÏfiÁˆ Ï‹ÚÔ˘˜ ‡ÊÂÛ˘. ªÂÙ¿ 1 ¯ÚfiÓÔ ÂÎÙfi˜ ıÂڷ›·˜, ˘ÔÙÚÔ›·ÛÂ, ‰ÂÓ ·¿ÓÙËÛ ÛÙË Û˘Ì‚·ÙÈ΋ ıÂڷ›· Î·È ÌÂÙ·ÎÈÓ‹ıËΠÛÙËÓ ÔÌ¿‰· ÙÔ˘ AD. ∆¤ÏÔ˜, ÛÙÔÓ 4Ô ¯ÚfiÓÔ ıÂڷ›·˜, 87,5% ÙˆÓ ·ÛıÂÓÒÓ ¤Ù˘¯·Ó ACRped 50-70 Î·È ÔÈ 3 ‰È¤ÎÔ„·Ó ÏfiÁˆ ‡ÊÂÛ˘ Ù˘ ÓfiÛÔ˘ (2) ‹ ˘ÔÙÚÔ‹˜ (1). √ ÙÂÏÂ˘Ù·›Ô˜ ›¯Â ˘ÔÙÚÔÈ¿ÛÂÈ Î·È fiÙ·Ó ‹Ù·Ó ·Ú¯Èο ÛÙËÓ ÔÌ¿‰· ÙÔ˘ ∂∆. ¢‡Ô ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Û˘Ó¯›˙Ô˘Ó ÙË ıÂڷ›· ÙÔ˘˜ ÁÈ· 5Ô ¯ÚfiÓÔ (‰ÂÓ ÙÔÓ Û˘ÌÏ‹ÚˆÛ·Ó) Î·È ‰È·ÙËÚÔ‡Ó ÙËÓ Î·Ï‹ ·¿ÓÙËÛË Ô˘ ›¯·Ó ̤¯ÚÈ Û‹ÌÂÚ·. ™ÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÛıÂÓÒÓ, ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ 3ÂÙ›·˜, ÂÚÈÛÛfiÙÂÚÔÈ ·fi ÙÔ˘˜ ÌÈÛÔ‡˜ ·ÛıÂÓ›˜ (5562%) ¤Ù˘¯·Ó ¿ÚÈÛÙË ·¿ÓÙËÛË (ACRped 70) ›Ù Ì ÙÔ ¤Ó· ›Ù Ì ÙÔ ¿ÏÏÔ Û··ÛÌ·. £Âڷ›· Ì 3 Û˘Ó‰ڛ˜ ·ÓÙÈ-TNF: ¢‡Ô ·ÛıÂÓ›˜ ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙÔÓ ›‰ÈÔ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· ‰‡Ô ÊÔÚ¤˜, Û ‰È·ÊÔÚÂÙÈο ¯ÚÔÓÈο ‰È·ÛÙ‹Ì·Ù·, ÌÂÙ¿ ·fi ·ÔÙ˘¯›· ÛÙÔÓ ¿ÏÏÔ, Ô ¤Ó·˜ ÙÔ ∂∆ Î·È Ô ¿ÏÏÔ˜ ÙÔ AD. √ ÚÒÙÔ˜ ·ÛıÂÓ‹˜ ¯ÚËÛÈÌÔÔ›ËÛ 2 ÊÔÚ¤˜ ÙÔ ∂∆. ∆Ô 2Ô fï˜ ¯ÚfiÓÔ ıÂڷ›·˜, ÂÌÊ¿ÓÈÛ ÁÈ· ÚÒÙË ÊÔÚ¿ π∫, ÛÙÔÓ 10Ô ¯ÚfiÓÔ Ù˘ ÓfiÛÔ˘, Ë ÔÔ›· ¤ÌÂÓ ·Ú¿ ÙË Û˘Ó¯‹ ÙÔÈ΋ ·ÁˆÁ‹ Ì ÛÙÂÚÔÂȉ‹
-40,5±80,1 -75 -58,9±42,4 -69,2 -64,5±38,4 -77,1 3,65±124,8 -43,3 37,9±299,7 -70,8 -64,4±47,1 -100 -5±202,5 -66,6 -5±202,4 -66,6
∂ÈÎfiÓ· 2. ∂Ù‹ÛÈ· ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ Adalimumab Û‡Ìʈӷ Ì ٷ ÎÚÈÙ‹ÚÈ· ACRped.
-1,6±3,2 -3 -5,3±6,8 -4 -5,4±5,7 -4 -10,8±36,1 -10,9 -16,3±76,7 -21,9 -0,3±0,4 -0,2 -2±3 -3 -2±2,9 -3
4
-61,3±96,9 -100 -63,6±57,2 -83,3 -80,1±26,5 94 -41±47,6 -51,6 -11,6±195,3 -83,5 -58,1±54,9 -85,7 -71,5±39,4 -93,3 -71,5±39,4 -93,3
2 3 ÃÚfiÓÈ· ıÂڷ›·˜
-3,3±5 -4 -5,7±8 -4 -5,2±6 -4 -19,8±24,5 -17 -25,7±42,8 -24 -0,4±0,5 -0,2 -2,5±1,9 -2,7 -2,4±1,8 -2,7
1
3 (N=10) ‚ (%)
0%
·
20%
ÃÚfiÓÔ˜
40%
·
ACR <30 ACR 30 ACR 50 ACR 70
60%
4±4 4 8,7±8,2 6 9,3±8,3 6 42,9±21,6 42,5 39±41,6 25 0,5±5,5 0,5 3,9±1,8 4 3,9±1,8 4
80%
∞Ú. ‰ÈÔÁÎˆÌ¤ÓˆÓ ·ÚıÚÒÛÂˆÓ (x±SD, median) ∞Ú. ÂÒ‰˘ÓˆÓ ·ÚıÚÒÛÂˆÓ (x±SD, median) ∞Ú. ·ÚıÚÒÛÂˆÓ Ì ÂÓÂÚÁfi ÓfiÛÔ (x±SD, median) ∆∫∂ (x±SD, median) CRP (x±SD, median) ¢Â›ÎÙ˘ ªÂÈÔÓÂÎÙÈÎfiÙËÙ·˜ (CHAQ) (0-3) (x±SD, median) ™Ê·ÈÚ. ∂ÎÙ›ÌËÛË π·ÙÚÔ‡ (0-10) (x±SD, median) ™Ê·ÈÚ. ∂ÎÙ›ÌËÛË ∂˘ÂÍ›·˜ ·fi ÙÔ˘˜ ÁÔÓ›˜ (0-10) (x±SD, median)
4 (N=8)** ‚ (%)
N=8
2 (N=15) · ‚ (%)
N=10
1 (N=22) ·* ‚ (%)
N=15
ŒÓ·ÚÍË ıÂڷ›·˜
N=21
¶›Ó·Î·˜ 4. ∂Ù‹ÛÈ· ÂÎÙ›ÌËÛË Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ÙÔ˘ Adalimumab, Ì ‚¿ÛË Ù· ηıÈÂڈ̤ӷ ÎÚÈÙ‹ÚÈ· ÛÙÔ˘˜ 21 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘. ™‡ÓÔÏÔ ıÂڷ¢ÙÈÎÒÓ Û˘Ó‰ÚÈÒÓ: 22
¶ÔÛÔÛÙfi ·ÛıÂÓÒÓ
100%
-2,4±3,7 -51,5±86 -4 -100 -7,6±10,8 -70,5±48,2 -4 -95,8 -7,3±12 -60,4±63,7 -4 -95,8 -4,4±16,9 -3,6±56,3 2 0 -27±23,7 -71,3±55,1 -30 -86,5 -0,3±0,5 -61,6±42,7 -0,3 -61,6 -2,5±2,4 -24,4±144,3 -4,5 -25 -2,5±2,4 -24,3±144,2 -3 -75
¶ÂÓÙ·ÂÙ‹˜ ÂÌÂÈÚ›· ·fi ÙË ¯Ú‹ÛË etanercept Î·È adalimumab ÛÙË Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·
¶·È‰È·ÙÚÈ΋ 2009;72:29-40
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·36
36
ª. ∆Ú·¯·Ó¿ Î·È Û˘Ó.
¶›Ó·Î·˜ 5. ¢È·¯ÚÔÓÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ 46 ·ÛıÂÓÒÓ ˘fi ·ÓÙÈ-TNF ıÂڷ›· (Etanercept N=32, Adalimumab N=14)
ŒÓ·ÚÍË ıÂڷ›·˜ (·Ú. ·ÛıÂÓÒÓ) £Âڷ¢ÙÈΤ˜ Û˘Ó‰ڛ˜ ÛÙÔ˘˜ ·ÛıÂÓ›˜ 1Ô˜ ¯ÚfiÓÔ˜ ACRped 50-70 ACRped 30 ACRped<30 2Ô˜ ¯ÚfiÓÔ˜ ¢ÂÓ Û˘ÌÏ. 2 ¯ÚfiÓÈ·* ACRped 50-70 ACRped 30 ACRped<30 IK-‰È·ÎÔ‹ ⁄ÊÂÛË-‰È·ÎÔ‹ 3Ô˜ ¯ÚfiÓÔ˜ ¢ÂÓ Û˘ÌÏ. 3 ¯ÚfiÓÈ·* ACRped 50-70 ACRped 30 ⁄ÊÂÛË-‰È·ÎÔ‹ 4Ô˜ ¯ÚfiÓÔ˜ ¢ÂÓ Û˘ÌÏ. 4 ¯ÚfiÓÈ·* ACRped 50-70 ACRped 30 ACRped <30 ⁄ÊÂÛË-‰È·ÎÔ‹ 5Ô˜ ¯ÚfiÓÔ˜ ¢ÂÓ Û˘ÌÏ. 5 ¯ÚfiÓÈ·* ACRped 50-70 ACRped 30 ACRped<30 ⁄ÊÂÛË-‰È·ÎÔ‹ IK-‰È·ÎÔ‹
ªfiÓÔ ∂∆
∂∆ ·fi ·ÏÏ·Á‹ ÔÌ¿‰·˜
™‡ÓÔÏÔ ∂∆
ªfiÓÔ AD
AD ·fi ·ÏÏ·Á‹ ÔÌ¿‰·˜
™‡ÓÔÏÔ AD
32
4
36
14
7
21
32 32 28 4 0 29
5 4 4 0 0 3
37 36 32 4 0 32
14 14 11 1 2 10
24 4 1 0 5 18 4* 15 3 3 10 5* 8 0 2 2 8
2 0 0 1 0 0 3*
26 4 1 1 5 18 7* 15 3 3 10 5* 8 0 2 2 8
7 1 2 0 0 7 1* 7 0 0 6
8 7 4 2 1 5 1* 3 1 1 0 0 3 1* 3 0 1 2 1* 1 0 1 0
22 21 15 3 3¨ 15 3* 10 2 3¨ 0 0 10 2* 10 0 1 8 1* 7 0 1 2 2 2*
6 2 0 2 1
6 0 0 2
6 2 0 2 1
ET: Etanercept, AD: Adalimumab * ¢ÂÓ Û˘ÌÏ‹ÚˆÛ·Ó ÙÔÓ ÚÔ‚ÏÂfiÌÂÓÔ ¯ÚfiÓÔ ·Ú·ÎÔÏÔ‡ıËÛ˘, ·ÏÏ¿ Û˘Ó¯›˙Ô˘Ó ÙË ıÂڷ›· ¨ ∞ÏÏ·Á‹ ·ÓÙÈ-TNF
Î·È Ì˘‰ÚÈ·ÙÈο Ê¿Ú̷η › 3 Ì‹Ó˜ Î·È ·Ó·ÁηÛÙÈο ‰È¤ÎÔ„Â ÙËÓ ·ÁˆÁ‹ Ì ∂∆. ∏ ¿ÏÏË ·ÛıÂÓ‹˜ ‹Ù·Ó ·˘Ù‹ Ô˘ η٤ÏËÍ 2 Ì‹Ó˜ ÌÂÙ¿ ÙËÓ ·ÏÏ·Á‹ ·fi ∂∆ Û AD (ÁÈ· 2Ë ÊÔÚ¿), ÏfiÁˆ ÂÌÊ¿ÓÈÛ˘ π∫. ∂›‰Ú·ÛË Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜ ÛÙË Û˘Á¯ÔÚ‹ÁËÛË ÛÙÂÚÔÂȉÒÓ: ™ÙȘ 18/25 (72%) ıÂڷ¢ÙÈΤ˜ Û˘Ó‰ڛ˜, ÔÈ ·ÛıÂÓ›˜ Ô˘ ¿Ú¯ÈÛ·Ó ·ÓÙÈ-TNF ıÂڷ›· Ì ·Ú¿ÏÏËÏË ¯ÔÚ‹ÁËÛË PDN ‰È¤ÎÔ„·Ó ÛÙ·‰È·Î¿ Ù· ÛÙÂÚÔÂȉ‹ ̤۷ Û 6 Ì‹Ó˜ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜ Î·È ÛÙȘ ˘fiÏÔȘ 7/25 Û˘Ó¤¯ÈÛ·Ó Û Ôχ ¯·ÌËÏ‹ ‰fiÛË, 0,1 mg/kg/ËÌ. Û ·Ú‹ÌÂÚÔ Û¯‹Ì·, ̤¯ÚÈ ÙÔ Ù¤ÏÔ˜ Ù˘ ÌÂϤÙ˘, ÏfiÁˆ ÂÈÌÔÓ‹˜ Ù˘ ÓfiÛÔ˘. ∂›‰Ú·ÛË Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜ ÛÙËÓ Â›Ù¢ÍË Ï‹ÚÔ˘˜ ‡ÊÂÛ˘: ∆Ô ¤Ó· ÙÚ›ÙÔ ÙˆÓ ·ÛıÂÓÒÓ (30,5%) Ô˘ ¿Ú¯ÈÛ·Ó ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ 14/46 (ET=12, Paediatriki 2009;72:29-40
AD=3) - ¤Ó·˜ ·ÛıÂÓ‹˜ ·Ó‹ÎÂ Î·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ ‰È¤ÎÔ„·Ó ÙË ıÂڷ›· ÏfiÁˆ Ï‹ÚÔ˘˜ ‡ÊÂÛ˘ ÁÈ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 2 ¯ÚfiÓÈ· (2-4). ∏ ·¿ÓÙËÛË ·˘Ù‹ ÛÙËÓ ·ÓÙÈTNF ·ÁˆÁ‹ ÛÙËÓ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ ·Ú·ÙËÚ‹ıËΠÛÙ· ÚÒÙ· 2-3 ¯ÚfiÓÈ· Ù˘ ıÂڷ›·˜. √È 10/14 (71,5%) fï˜, 2-6 Ì‹Ó˜ ÌÂÙ¿ ÙË ‰È·ÎÔ‹ ÙÔ˘ ·ÓÙÈTNF, ÂÌÊ¿ÓÈÛ·Ó ¤Í·ÚÛË Ù˘ ÓfiÛÔ˘, Ì ÎÏÈÓÈ΋ ÂÈÎfiÓ· ËÈfiÙÂÚË Û ۯ¤ÛË Ì ÙËÓ ÂÈÎfiÓ· ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜. ∞ÓÙÈÌÂÙˆ›ÛıËÎ·Ó Ì ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘ ¿ÏÏÔ˘ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· (4/10) ‹ ÌÂ Û˘Ó‰˘·ÛÌfi 2 DMARDs Ì ‹ ¯ˆÚ›˜ ÛÙÂÚÔÂȉ‹ (6/10). ∞fi ÙÔ˘˜ ˘fiÏÔÈÔ˘˜ 4 ·ÛıÂÓ›˜ Ô˘ ·Ú·Ì¤ÓÔ˘Ó Û ϋÚË ‡ÊÂÛË ¯ˆÚ›˜ ıÂڷ›·, ÔÈ 2 ¤¯Ô˘Ó ‹‰Ë Û˘ÌÏËÚÒÛÂÈ ÙÔ˘Ï¿¯ÈÛÙÔÓ 2 ¯ÚfiÓÈ· ‡ÊÂÛ˘. ∂›‰Ú·ÛË Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜ ÛÙË Û˘ÛÙËÌ·ÙÈ΋ ÌÔÚÊ‹ Ù˘ ¡π∞: √È 9/46 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·37
37
¶ÂÓÙ·ÂÙ‹˜ ÂÌÂÈÚ›· ·fi ÙË ¯Ú‹ÛË etanercept Î·È adalimumab ÛÙË Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·
›¯·Ó Û˘ÛÙËÌ·ÙÈ΋ ¡IA (4/9 Ì ÚÔ¤¯Ô˘Û˜ ÙȘ Û˘ÛÙËÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ Î·È 5/9 Ì ÂÈÎfiÓ· ÔÏ˘·ÚıÚ›Ùȉ·˜ ÛÙËÓ ÔÚ›·. √È 7/9 ¤Ù˘¯·Ó ACRped 50-70 Ì ¤Ó·Ó (5/7) ‹ 2 ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ (2/7) Î·È ÔÈ 2/9 ›¯·Ó Ùˆ¯‹ ·¿ÓÙËÛË (ACRped ≤30). ™˘ÓÔÏÈο, 5 ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË ·ÁˆÁ‹˜ Ì ∂∆ ‹ AD, Ë ÂÎÙ›ÌËÛË Â›Ó·È fiÙÈ Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ (42/46, 91,3%) ˆÊÂÏ‹ıËÎ·Ó ÛËÌ·ÓÙÈο ·fi Ù· Û˘ÁÎÂÎÚÈ̤ӷ ·ÓÙÈ-TNF Û΢¿ÛÌ·Ù· (›Ù ·fi ÙÔ ¤Ó· ›Ù ·fi ÙÔ ¿ÏÏÔ Â›ÙÂ Î·È ·fi Ù· ‰‡Ô), ·ÊÔ‡ ¤Ù˘¯·Ó Ï‹ÚË ‡ÊÂÛË (30,5%) ‹ ACRped 5070 (60,86%) ÌÂÙ¿ 2-4 ¯ÚfiÓÈ·. √È 4/46 (8,7%) ‰ÂÓ ·¿ÓÙËÛ·Ó ÈηÓÔÔÈËÙÈο (ACRped ≤30) ηÈ, fiˆ˜ ÚԷӷʤÚıËÎÂ, ÔÈ ÌÈÛÔ› ·Ó‹Î·Ó ÛÙÔ Û˘ÛÙËÌ·ÙÈÎfi Ù‡Ô ¤Ó·Ú͢ Ù˘ ÓfiÛÔ˘, Ì ÌÂٿوÛË Û ›ÌÔÓË ‰È·‚ÚˆÙÈ΋ ÔÏ˘·ÚıÚ›Ùȉ·.
™˘˙‹ÙËÛË ∏ ÌÂϤÙË ·˘Ù‹ ·ÔÙÂÏ› ÙËÓ ÚÒÙË ·ÔÙ›ÌËÛË Ù˘ 5ÂÙÔ‡˜ ÂÌÂÈÚ›·˜ ˆ˜ ÚÔ˜ ÙËÓ ·ÛÊ¿ÏÂÈ· Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ¯ÔÚ‹ÁËÛ˘ ‰‡Ô ·ÓÙÈ-TNF ·Ú·ÁfiÓÙˆÓ - ∂∆ Î·È AD - Û ·È‰È¿ Ì ¡π∞ ÛÙË ¯ÒÚ· Ì·˜. ∞Ó¿ÏÔÁË Ì·ÎÚÔ¯ÚfiÓÈ· ‰ËÌÔÛÈÂ˘Ì¤ÓË ÂÌÂÈÚ›· ÁÈ· ÌÂÓ ÙÔ ∂∆ ‰ËÌÔÛȇıËΠ·fi ÙÔ˘˜ Lovell Î·È Û˘Ó. (12) Û ·È‰È¿ Ì ÔÏ˘·ÚıÚÈ΋ ÔÚ›· NIA Î·È 4ÂÙ‹ ·Ú·ÎÔÏÔ‡ıËÛË, ÁÈ· ‰Â ÙÔ AD ‰ËÌÔÛȇıËΠÚfiÛÊ·Ù·, ·fi ÙÔ˘˜ Biester Î·È Û˘Ó. (17) Î·È ÙÔ˘˜ Tynjala Î·È Û˘Ó. (18), 3ÂÙ‹˜ ÂÌÂÈÚ›· ˆ˜ ÚÔ˜ ÙËÓ Â›‰Ú·Û‹ ÙÔ˘ ÛÙË ¡π∞ Î·È ÛÙËÓ π∫. ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, Î·È Ù· ‰‡Ô Û΢¿ÛÌ·Ù· ·Ô‰Â›¯ıËÎ·Ó ·ÛÊ·Ï‹ ÛÙËÓ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ. ™Ô‚·Ú¤˜ ÏÔÈÌÒÍÂȘ ηٷÁÚ¿ÊËÎ·Ó ÌfiÓÔ Û 2/46 ·ÛıÂÓ›˜ (4,34%), ÔÈ ÔÔ›ÔÈ ¯ÚÂÈ¿ÛıËÎ·Ó ÓÔÛËÏ›·. √ ¤Ó·˜ ·ÛıÂÓ‹˜ ˘fi ∂∆ ÓfiÛËÛ ·fi ¤ÚËÙ· ˙ˆÛÙ‹Ú· Ì ·Ú·ÙÂٷ̤ÓË ÔÚ›· Ô˘ ¯ÚÂÈ¿ÛıËΠ·ÁˆÁ‹ Ì ·Î˘ÎÏÔ‚›ÚË. ∏ ¿ÏÏË ·ÛıÂÓ‹˜, ÌÂÙ¿ ·fi 2ÌËÓË ıÂڷ›· Ì AD Î·È ÚÔËÁÔ‡ÌÂÓË 2ÂÙ‹ ıÂڷ›· Ì ÙÔÓ ›‰ÈÔ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· (AD) Î·È ÛÙË Û˘Ó¤¯ÂÈ· Ì ∂∆, ÓfiÛËÛ ·fi ÛÔ‚·Ú‹ Ïԛ̈ÍË Èı·ÓfiÓ ÙÔ˘ ∫¡™, Î·È Î·Ù¤ÏËÍ ÂÓÙfi˜ 2 ËÌÂÚÒÓ ·fi ÙËÓ Â›Û΄‹ Ù˘ Û ÓÔÛÔÎÔÌÂ›Ô Ù˘ ÂÚÈʤÚÂÈ·˜, Ì ‹‰Ë ÂÁηÙÂÛÙË̤ÓË ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·. ∏ ·ÎÚÈ‚‹˜ ·ÈÙ›· ÙÔ˘ ı·Ó¿ÙÔ˘ ·Ú·Ì¤ÓÂÈ ·‰È¢ÎÚ›ÓÈÛÙË ÁÈ·Ù›, fiˆ˜ ÚԷӷʤÚıËÎÂ, ‰ÂÓ ¤ÁÈÓ ÓÂÎÚÔÙÔÌ‹. √È Lovell Î·È Û˘Ó. (12,19,20) ·Ó·Ê¤ÚÔ˘Ó ÛÙË ÌÂϤÙË ÙÔ˘˜ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ÛÔ‚·ÚÒÓ ÏÔÈÌÒÍÂˆÓ (12%), Èı·Ófiٷٷ ÏfiÁˆ ÙÔ˘ ÌÂÁ·Ï‡ÙÂÚÔ˘ ·ÚÈıÌÔ‡ ·ÛıÂÓÒÓ (n=58) Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ·Ó Ì·ÎÚÔ¯ÚfiÓÈ·. ◊Ș ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ, fiˆ˜ ÎÔÈÓ¤˜ ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ ‹/Î·È ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡, ÂÌÊ·Ó›ÛıËÎ·Ó Û 17/59 (28,81%) ·ÓÙÈ-TNF Û˘Ó‰ڛ˜ (10/37 Ì ∂∆ Î·È 7/22 Ì AD) Ô˘ ¤Ï·‚·Ó ÔÈ ·ÛıÂÓ›˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘, ÂÓÒ ÔÈ ÙÔÈΤ˜ ηÈ
Û˘ÛÙËÌ·ÙÈΤ˜ ·ÏÏÂÚÁÈΤ˜ ·ÓÙȉڿÛÂȘ Ô˘ ·ÊÔÚÔ‡Û·Ó ·ÔÎÏÂÈÛÙÈο ÙËÓ ÔÌ¿‰· ÙÔ˘ AD ‹Ù·Ó ÂÏ¿¯ÈÛÙ˜: 1/59 (1,6%) Î·È 2/59 (3,4%). ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÏÔÈÌÒÍÂˆÓ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ Â›Ó·È ·ÚfiÌÔÈ· (35%) Ì ·˘Ù‹ Ô˘ ·Ó·Ê¤ÚÂÙ·È ÛÙȘ ÌÂϤÙ˜ ÙˆÓ Lovell Î·È Û˘Ó. (12, 19, 20), ÂÓÒ Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÙÔÈÎÒÓ ·ÏÏÂÚÁÈÎÒÓ ·ÓÙȉڿÛÂˆÓ ‹Ù·Ó Ôχ ÌÈÎÚfiÙÂÚË ·fi ÙËÓ ·Ó·ÊÂÚfiÌÂÓË ÛÙȘ ·Ú·¿Óˆ ÌÂϤÙ˜ (39%) (12,19). ™˘ÛÙËÌ·ÙÈΤ˜ ·ÏÏÂÚÁÈΤ˜ ·ÓÙȉڿÛÂȘ ‹ ı¿Ó·ÙÔ˜ ‰ÂÓ ·Ó·Ê¤ÚÔÓÙ·È Û η̛· ·fi ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜. ∞Ó¿ÏÔÁË Û˘¯ÓfiÙËÙ· ·ÓÂÈı‡ÌËÙˆÓ ·ÓÙȉڿÛÂˆÓ Ì ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Î·Ù·ÁÚ¿ÊÂÙ·È Î·È Û ÁÂÚÌ·ÓÔ-·˘ÛÙÚȷ΋ ÌÂϤÙË (ÔÛÔÛÙfi 3,4% ), ÂÓÒ Û ̛· Á·ÏÏÈ΋ ÌÂϤÙË Î·Ù·ÁÚ¿ÊÂÙ·È 5Ï¿ÛÈ· Û˘¯ÓfiÙËÙ· (20%) (21,22). ∏ ·ÚÔ˘Û›· ·ÓÂÈı‡ÌËÙˆÓ ·ÓÙȉڿÛÂˆÓ ·Ó¿ÁηÛ 4/46 ·ÛıÂÓ›˜ Ó· ‰È·Îfi„Ô˘Ó ÙÔÓ ·ÓÙÈ-TNF, ÙÔ AD ‹ ÙÔ ∂∆ Î·È Ë ·ÈÙ›· ‹Ù·Ó: Û˘ÛÙËÌ·ÙÈΤ˜ ·ÏÏÂÚÁÈΤ˜ ·ÓÙȉڿÛÂȘ, fiˆ˜ ÂÍ¿ÓıËÌ· Î·È ÎÓËÛÌfi˜ (2), ‰È·Ù·Ú·¯¤˜ ÂÌÌ‹ÓÔ˘ Ú‡Û˘ (1 ·ÛıÂÓ‹˜ ·fi ÙÔ˘˜ ÚÔ·Ó·ÊÂÚı¤ÓÙ˜ 2) Î·È ÂÌÊ¿ÓÈÛË π∫ (2). ∂›ÌÔÓË π∫, ˘fi ·ÓÙÈ-TNF ıÂڷ›· Ì ET, ·Ó¤Ù˘Í·Ó 2/46 (4,34%) ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ Ì·˜, 10 Î·È 15 ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ¡π∞, ÁÂÁÔÓfi˜ Ô˘ ·ÔÙ¤ÏÂÛ ÙËÓ ·ÈÙ›· ‰È·ÎÔ‹˜ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘. ∏ ÂÈÏÔ΋ ·˘Ù‹ ηٿ ÙË ‰È¿ÚÎÂÈ· ıÂڷ›·˜ Ì ∂∆ ·Ú·ÙËÚ‹ıËÎÂ Î·È ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜ (18,23), Û ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi (16,61%), Î·È ÙÔ˘˜ Ô‰‹ÁËÛ Û ·ÏÏ·Á‹ ÙÔ˘ ∂∆ Ì ¿ÏÏÔÓ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· (›Ù INFL ›Ù AD), Ú·ÎÙÈ΋ Ô˘ ·ÎÔÏÔ˘ı‹ıËÎÂ Î·È ÛÙÔ˘˜ 2 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ Ì·˜ (·fi ∂∆ Û AD). ªÂ ‚¿ÛË ÙËÓ ÂÌÂÈÚ›· ·˘Ù‹ Î·È ¿ÏÏ· ÚfiÛÊ·Ù· ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ, ˘ÈÔıÂÙ‹ıËΠ·fi ÙÔ Î¤ÓÙÚÔ Ì·˜ ˆ˜ ¿ÁÈ· Ù·ÎÙÈ΋ Ù· ÙÂÏÂ˘Ù·›· 2 ¯ÚfiÓÈ· Ù˘ ÌÂϤÙ˘ Ó· ÂÈϤÁÂÙ·È ˆ˜ ·ÓÙÈTNF ·Ú¿ÁÔÓÙ·˜ ÙÔ AD Û ·ÛıÂÓ›˜ Ì NIA Î·È ÂÓÂÚÁfi π∫ (17,18,25,26). ÕÏÏ· ·ÓÂÈı‡ÌËÙ· Û˘Ì‚¿Ì·Ù·, fiˆ˜ Ê˘Ì·Ù›ˆÛË ‹ ÔÙÈ΋ Ó¢ڛÙȉ·, Ô˘ ·Ô‰fiıËÎ·Ó ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜ ÛÙË ıÂڷ›· Ì INFL Î·È ∂∆ ·ÓÙ›ÛÙÔȯ·, ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË (27,28). ∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙˆÓ ‰‡Ô ·ÓÙÈ-TNF ·Ú·ÁfiÓÙˆÓ ‹Ù·Ó Ôχ ˘„ËÏ‹ ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË. ™˘ÓÔÏÈο 42/46 (91,3%) ·ÛıÂÓ›˜ ¤Ù˘¯·Ó ACRped 50-70 Ì’ ¤Ó·Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ ·fi Ù· 2 ·ÓÙÈ-TNF Û΢¿ÛÌ·Ù· Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËηÓ. ∆Ô ·ÔÙ¤ÏÂÛÌ· ·˘Ùfi ·ÍÈÔÏÔÁÂ›Ù·È ˆ˜ ȉȷ›ÙÂÚ· ÛËÌ·ÓÙÈÎfi, ·Ó Ï¿‚ÂÈ Î·Ó›˜ ˘fi„Ë ÙÔ˘ fiÙÈ fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ ›¯·Ó ÌÂÁ¿ÏË ‰È¿ÚÎÂÈ· ÓfiÛÔ˘ - ¿Óˆ ·fi 5 ¯ÚfiÓÈ· fiÙ·Ó ¿Ú¯ÈÛ·Ó ÙËÓ ·ÓÙÈ-TNF ıÂڷ›· - Î·È ‹Ù·Ó ·ÓıÂÎÙÈÎÔ› Û ÚÔËÁËı›۷ ¯ÔÚ‹ÁËÛË DMARDs. ¶·ÚfiÌÔÈ· ¢ÓÔ˚ο ·ÔÙÂϤÛÌ·Ù· ÂÚȤÁÚ·„·Ó Î·È ¿ÏÏÔÈ ¶·È‰È·ÙÚÈ΋ 2009;72:29-40
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·38
38
ª. ∆Ú·¯·Ó¿ Î·È Û˘Ó.
ÂÚ¢ÓËÙ¤˜ (15,21,22,29-31). ∏ ÔÏ˘ÎÂÓÙÚÈ΋ ÁÂÚÌ·ÓÔ-·˘ÛÙÚȷ΋ ÌÂϤÙË, Ô˘ ‰È‹ÚÎÂÛ ÏÈÁfiÙÂÚÔ ·fi ÙËÓ ·ÚÔ‡Û·, ·Ó·Ê¤ÚÂÈ fiÙÈ 80% ÙˆÓ ·ÛıÂÓÒÓ ˘fi ∂∆ ¤Ù˘¯·Ó ACRped 30 (22), ÔÛÔÛÙfi ·Ó¿ÏÔÁÔ Ì’ ·˘Ùfi ÙˆÓ Lovell Î·È Û˘Ó. (20) ÛÙ· 2 ¯ÚfiÓÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ (81% ¤Ù˘¯·Ó ACRped 30). ∂ÂÎÙ›ÓÔÓÙ·˜, fï˜, ÙË ÌÂϤÙË ÙÔ˘˜ ÔÈ Lovell Î·È Û˘Ó. Û 4 ¯ÚfiÓÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ Î·È ·ÍÈÔÏÔÁÒÓÙ·˜ ÙȘ › ̤ÚÔ˘˜ ·Ú·Ì¤ÙÚÔ˘˜ ‚ÂÏÙ›ˆÛ˘ Ù˘ ÓfiÛÔ˘, Ô˘ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙ· ACRped ÎÚÈÙ‹ÚÈ·, ·Ó·Ê¤ÚÔ˘Ó fiÙÈ, ·Ó¿ÏÔÁ· Ì ÙËÓ ·Ú¿ÌÂÙÚÔ, 16-63% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‹Ú·Ó ·ÔÎÏÂÈÛÙÈο ∂∆ ¤Ù˘¯·Ó Ï‹ÚË ‡ÊÂÛË (12). ŸÛÔÓ ·ÊÔÚ¿ ÙÔ ÓÂfiÙÂÚÔ Û ΢ÎÏÔÊÔÚ›· Û··ÛÌ· AD, Ôχ ÚfiÛÊ·Ù· ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ ·fi °ÂÚÌ·Ó›· (17) Î·È ºÈÓÏ·Ó‰›· (18), Ì ÌÈÎÚÔ‡˜ ·ÚÈıÌÔ‡˜ ·ÛıÂÓÒÓ (max 20) Î·È ÌÈÎÚfiÙÂÚÔ ¯ÚfiÓÔ ·Ú·ÎÔÏÔ‡ıËÛ˘, ·Ó·Ê¤ÚÔ˘Ó Â›Û˘ ˘„ËÏ¿ ÔÛÔÛÙ¿ ÂÈÙ˘¯›·˜ (55,6% Î·È 60% ·ÓÙ›ÛÙÔȯ·). ª›· ÂÈϤÔÓ ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË Ù˘ ·ÛÊ¿ÏÂÈ·˜ Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ÙÔ˘ AD ·fi ΤÓÙÚ· Ù˘ ∂˘ÚÒ˘ Î·È ÙˆÓ ∏¶∞ Ô˘ ¤¯ÂÈ ·Ó·ÎÔÈÓˆı› (·‰ËÌÔÛ›Â˘Ù· ‰Â‰Ô̤ӷ), Ì ÌÂÁ·Ï‡ÙÂÚÔ ‰Â›ÁÌ· ·ÛıÂÓÒÓ (¡=148), η٤ÁÚ·„ ·Ó¿ÏÔÁ· ¢ÓÔ˚ο ·ÔÙÂϤÛÌ·Ù· ÌÂÙ¿ ·fi 11 Ì‹Ó˜ ıÂڷ›·˜ (32). ∆Ô ˘„ËÏfiÙÂÚÔ ÔÛÔÛÙfi ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ÙˆÓ ·ÓÙÈ-TNF Û΢·ÛÌ¿ÙˆÓ ÛÙË ‰È΋ Ì·˜ ÌÂϤÙË ÔÊ›ÏÂÙ·È Ì¿ÏÏÔÓ ÛÙÔÓ ‰È·ÊÔÚÂÙÈÎfi ÙÚfiÔ ·ÍÈÔÏfiÁËÛ˘, Ë ÔÔ›· ¤ÁÈÓ Ì ‚¿ÛË ÙÔ ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· Ù˘ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ¯ÔÚ‹ÁËÛ˘ Ì›·˜, ‰‡Ô ‹ Î·È ÙÚÈÒÓ ıÂڷ¢ÙÈÎÒÓ Û˘Ó‰ÚÈÒÓ (59 Û˘Ó‰ڛ˜ Û 46 ·ÛıÂÓ›˜). ¢È·¯ÚÔÓÈο, ·Ú·ÙËÚ‹ıËΠÌÈ· ÂÏ·ÊÚÒ˜ Êı›ÓÔ˘Û· ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È ÙˆÓ 2 ·ÓÙÈ-TNF Û΢·ÛÌ¿ÙˆÓ. ™ÙËÓ ÂÙ‹ÛÈ· ÂÎÙ›ÌËÛË ÙÔ˘ ∂∆, ÙÔ ACRped 50-70 ÙˆÓ ·ÛıÂÓÒÓ ÂÏ·ÙÙÒıËΠ·fi 88,9% Û 75% ·fi ÙÔÓ 1Ô ÛÙÔÓ 5Ô ¯ÚfiÓÔ, ÔÛÔÛÙfi ˆÛÙfiÛÔ È‰È·›ÙÂÚ· ÈηÓÔÔÈËÙÈÎfi Ì ‚¿ÛË ÙËÓ ÂÈÏÔÁ‹ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ›¯·Ó ·ÓıÂÎÙÈ΋ ÓfiÛÔ. ∏ ·ÓÙ›ÛÙÔÈ¯Ë ·Ú·Ù‹ÚËÛË ›Û¯˘ÛÂ Î·È ÁÈ· Ù· 2 ÚÒÙ· ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ AD (·fi 71,4% Û 66,7%). ∞Ó¿ÏÔÁË ÂÌÂÈÚ›· ÂÚÈÁÚ¿ÊÂÙ·È Î·È ÛÙË Á·ÏÏÈ΋ ÌÂϤÙË ·ÛıÂÓÒÓ ˘fi ∂∆ (22). ¶Èı·ÓÔÏÔÁÂ›Ù·È Ë ·Ó¿Ù˘ÍË ÂÍÔ˘‰ÂÙÂÚˆÙÈÎÒÓ ÚÔ˜ ÙÔÓ ·ÓÙÈ-TNF ·ÓÙÈۈ̿وÓ, Ô˘ ÌÂÈÒÓÔ˘Ó ¤ÙÛÈ ÙË ‰Ú·ÛÙÈÎfiÙËÙ¿ ÙÔ˘ (22). ª›· ÂÈϤÔÓ ¤Ó‰ÂÈÍË Ù˘ ¢ÓÔ˚΋˜ ‰Ú¿Û˘ ÙˆÓ ·ÓÙÈ-TNF Û΢·ÛÌ¿ÙˆÓ ‹Ù·Ó Î·È Ë ÛÙ·‰È·Î‹ ‰È·ÎÔ‹ ÙˆÓ ÛÙÂÚÔÂȉÒÓ Ì¤Û· Û 6 Ì‹Ó˜ ÛÙȘ 18/25 ıÂڷ¢ÙÈΤ˜ Û˘Ó‰ڛ˜ (72%). √È Lovell Î·È Û˘Ó. ·Ó·Ê¤ÚÔ˘Ó ·Ó¿ÏÔÁÔ ÔÛÔÛÙfi (80%) ÛÙËÓ ÙÂÙÚ·ÂÙ‹ ÂÌÂÈÚ›· ÙÔ˘˜ (12). ∆Ô 1/3 ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ (30,5%) ‰È¤ÎÔ„Â ÙËÓ ·ÓÙÈ-TNF ıÂڷ›· ÏfiÁˆ Ï‹ÚÔ˘˜ ‡ÊÂÛ˘ ÌÂÙ¿ ·fi 1 (14) ‹ 2 (1) ·ÓÙÈ-TNF Û˘Ó‰ڛ˜ (¤Ó·˜ ·ÛıÂPaediatriki 2009;72:29-40
Ó‹˜ ›¯Â ‡ÊÂÛË Î·È Ì ÙÔ˘˜ ‰‡Ô ·ÓÙÈ-TNF, ÙÔ˘˜ ÔÔ›Ô˘˜ ‹Ú Ì ÌÂÛԉȿÛÙËÌ· 16 ÌËÓÒÓ ÂÚ›Ô˘). √È 10/14 Ô˘ ˘ÔÙÚÔ›·Û·Ó ÌÂÙ¿ ÙË ‰È·ÎÔ‹ ÙÔ˘ ∂∆ ‹ ÙÔ˘ AD ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ 5ÂÙ›·˜ ›¯·Ó ËÈfiÙÂÚË ÂÈÎfiÓ· ·’ ·˘Ù‹Ó Ô˘ ›¯·Ó ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ·ÓÙÈ-TNF ıÂڷ›·˜. ∆Ô ÁÂÁÔÓfi˜ ·˘Ùfi, Ô˘ ·Ú·ÙËÚ‹ıËÎÂ Î·È ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜, (33,34) Ì·˜ ÚÔ‚ÏËÌ·Ù›˙ÂÈ ˆ˜ ÚÔ˜ ÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô˘ Ú¤ÂÈ Ó· ‰È·ÙËÚËı› Ë ·ÓÙÈ-TNF ıÂڷ›· ÌÂÙ¿ ÙËÓ Â›Ù¢ÍË Ï‹ÚÔ˘˜ ‡ÊÂÛ˘, ÚÔÎÂÈ̤ÓÔ˘ Ë ‡ÊÂÛË ·˘Ù‹ Ó· Â›Ó·È Ì·ÎÚÔ¯ÚfiÓÈ·. ∏ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ Ô˘ ·ÚÔ˘Û›·Û ȉȷ›ÙÂÚË ·ÓıÂÎÙÈÎfiÙËÙ· ÛÙËÓ ·ÓÙÈ-TNF ·ÁˆÁ‹ ‹Ù·Ó Ë Û˘ÛÙËÌ·ÙÈ΋ ÌÔÚÊ‹ Ì ÔÚ›· ÔÏ˘·ÚıÚ›Ùȉ·˜ (ÂÍ·Ú¯‹˜ ÌË ·¿ÓÙËÛË ‹ ˘ÔÙÚÔ‹ ηٿ ÙËÓ ÔÚ›· ‹ ˘ÔÙÚÔ‹ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË ‰È·ÎÔ‹ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ıÂڷ›·˜). ŒÙÛÈ, 2/9 ·ÛıÂÓ›˜ ÌÂ Û˘ÛÙËÌ·ÙÈ΋ ÌÔÚÊ‹ ‰ÂÓ ·¿ÓÙËÛ·Ó ÛÙËÓ ·ÓÙÈ-TNF ıÂڷ›·, ÂÓÒ Ô ·ÓÙ›ÛÙÔȯԘ ·ÚÈıÌfi˜ ÛÙÔ˘˜ 46 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó 4/46 (p=0,003) (35,36). ™˘ÌÂÚ·ÛÌ·ÙÈο, Ù· Â˘Ú‹Ì·Ù· ·˘Ù¿ ‰Â›¯ÓÔ˘Ó: ·) ∆Ë Ì·ÎÚÔ¯ÚfiÓÈ· ·ÛÊ¿ÏÂÈ· Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ ET Î·È AD, ·ÏÏ¿ Î·È ÙËÓ Â›Ù¢ÍË ‡ÊÂÛ˘ Ì ÙË ¯ÔÚ‹ÁËÛË ÙˆÓ 2 ·˘ÙÒÓ ·Ú·ÁfiÓÙˆÓ. øÛÙfiÛÔ ··ÈÙÂ›Ù·È Â·ÁÚ‡ÓËÛË ÁÈ· ÙÔ ÂӉ¯fiÌÂÓÔ ÛÔ‚·ÚÒÓ ÏÔÈÌÒÍÂˆÓ Ô˘ ÌÔÚ› Ó· ¤¯Ô˘Ó ÌÔÈÚ·›· ¤Î‚·ÛË. ‚) ∆Ë ‰˘Ó·ÙfiÙËÙ· Ù˘ ÂÈÙ˘¯Ô‡˜ ÌÂٷΛÓËÛ˘ ·fi ÙÔÓ ¤Ó· ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· ÛÙÔÓ ¿ÏÏÔ Û ÂÚ›ÙˆÛË ·ÔÙ˘¯›·˜ ‹ Êı›ÓÔ˘Û·˜ ·¿ÓÙËÛ˘ ‹ ˘ÔÙÚÔ‹˜ ÌÂÙ¿ ·fi ‡ÊÂÛË. Á) ∆ËÓ Â˘ÓÔ˚΋ ›‰Ú·ÛË ÙÔ˘ AD ÛÙËÓ π∫. ‰) ø˜ ÚÔ˜ ÙËÓ ÔÏÈÙÈ΋ ·ӷ¯ÔÚ‹ÁËÛ˘ ÌÂÙ¿ ·fi ¯ÚfiÓÈ· ÙÔ˘ ·Ú¯ÈÎÔ‡ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ· Ô˘ ¯ÔÚËÁ‹ıËÎÂ, ‰ÂÓ ÂÍ¿ÁÂÙ·È Î·Ó¤Ó· Û˘Ì¤Ú·ÛÌ·, ÏfiÁˆ ÙÔ˘ ÌÈÎÚÔ‡ ·ÚÈıÌÔ‡ ÙˆÓ ·ÛıÂÓÒÓ (¡=2). ∂ÈϤÔÓ, Ù· Â˘Ú‹Ì·Ù· Ù˘ ÌÂϤÙ˘ ÂȂ‚·ÈÒÓÔ˘Ó ÙË ‰˘Ó·ÙfiÙËÙ· Ù˘ ÂÈÏÔÁ‹˜ ÙÔ˘ ∂∆ Î·È ÙÔ˘ AD ˆ˜ Ì›· ·ÎfiÌË ÂÓ·ÏÏ·ÎÙÈ΋ ıÂڷ›· ÁÈ· ÔÚÈṲ̂Ó˜ ÌÔÚʤ˜ ¡π∞ (›ÌÔÓ· ÔÏÈÁÔ·ÚıÚÈΤ˜, ÔÏ˘·ÚıÚÈΤ˜) Ô˘ Â›Ó·È ·ÓıÂÎÙÈΤ˜ ÛÙË Û˘Ì‚·ÙÈ΋ ıÂڷ›·, Ë ÔÔ›· Ú¤ÂÈ Ó· ‰ÔÎÈÌ¿˙ÂÙ·È ÈÔ ¤ÁηÈÚ· ÛÙËÓ ÔÚ›· Ù˘ ÓfiÛÔ˘, ÙÔ˘Ï¿¯ÈÛÙÔÓ ÚÈÓ ÂÁηٷÛÙ·ı› ηٷÛÙÚÔÊÈ΋ ·ÚıÚÔ¿ıÂÈ·. ∂¿Ó Ë ·¿ÓÙËÛË ·ÓÙ·ÔÎÚ›ÓÂÙ·È ÛÙ· ‰ÈÂıÓ‹ ÎÚÈÙ‹ÚÈ· Ô˘ ηıÔÚ›˙Ô˘Ó ÙË ‚ÂÏÙ›ˆÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ (ACRped 30-70), Ë ıÂڷ›· ÌÔÚ› Ó· Û˘Ó¯›˙ÂÙ·È, ·ÏÏ¿ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ¿ Ù˘ Èı·ÓfiÓ Ó· ·ÚÔ˘ÛÈ¿˙ÂÈ Êı›ÓÔ˘Û· ÔÚ›·, fiˆ˜ Ê¿ÓËΠÛÙÔ˘˜ ‰ÈÎÔ‡˜ Ì·˜ ·ÛıÂÓ›˜. ¶·Ú·Ì¤ÓÂÈ ÏÔÈfiÓ Ô ÚÔ‚ÏËÌ·ÙÈÛÌfi˜ ÁÈ· fiÛÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÌÂÙ¿ ÙËÓ ÈηÓÔÔÈËÙÈ΋ ·¿ÓÙËÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ Ú¤ÂÈ Ó· Û˘Ó¯›ÛÔ˘Ì ÙË ¯ÔÚ‹ÁËÛË ÙÔ˘ ∂∆ ‹ AD (·Ó Ï¿‚ÂÈ Ì¿ÏÈÛÙ· ηÓ›˜ ˘fi„Ë ÙÔ˘ ÙÔ ˘„ËÏfi ÎfiÛÙÔ˜ ·˘Ù‹˜ Ù˘ ıÂڷ›·˜), ÒÛÙ ӷ ÌËÓ
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¶ÂÓÙ·ÂÙ‹˜ ÂÌÂÈÚ›· ·fi ÙË ¯Ú‹ÛË etanercept Î·È adalimumab ÛÙË Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·
ÙË ¯¿ÛÔ˘ÌÂ Î·È Ó· ÙË Û˘ÓÙËÚ‹ÛÔ˘Ì ˆ˜ ÌÈ· ÂÓ·ÏÏ·ÎÙÈ΋ ıÂڷ¢ÙÈ΋ ÛÙÚ·ÙËÁÈ΋ (33,37).
µÈ‚ÏÈÔÁÚ·Ê›· 1. ∫·Ó·ÎÔ‡‰Ë-∆۷ηϛ‰Ô˘ º, ∆Ú·¯·Ó¿ ª, ¶Ú·ÙÛ›‰Ô˘°Î¤ÚÙÛË ¶, µ·ÛÈÏÂÈ¿‰Ë˜ ∫. ∂Ê·ÚÌÔÁ‹ Ó¤·˜ ıÂڷ¢ÙÈ΋˜ ÛÙÚ·ÙËÁÈ΋˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ·ÓıÂÎÙÈÎÒÓ ÌÔÚÊÒÓ Ó·ÓÈ΋˜ ȉÈÔ·ıÔ‡˜ ·ÚıÚ›Ùȉ·˜. ¶·È‰È·ÙÚÈ΋ µÔÚ›Ԣ ∂ÏÏ¿‰Ô˜ 2002;14:48-56. 2. Gutcher I, Becher B. APC-derived cytokines and T-cell polarization in autoimmune inflammation. J Clin Invest 2007;117:1119-1127. 3. Choy CH, Panayi GS. Cytokine pathways and joint inflammation in Rheumatoid Arthritis. N Engl J Med 2001;344:907-916. 4. Chira P, Sandborg CI. Novel therapies in pediatric rheumatic diseases. Curr Opin Pediatr 2003;15:579-585. 5. Wilkinson N, Jackson G, Gardner-Medwin J. Biologic Therapies for juvenile arthritis. Arch Dis Child 2003;88: 186-191. 6. Murray KJ, Lovell DJ. Advanced therapy for juvenile arthritis. Best Pract Res Clin Rheumatol 2002;16:361-378. 7. Furst DE, Schiff MH, Fleischmann RM, Strand V, Birbara CA, Compagnone D, et al. Adalimumab, a fully human antitumor necrosis factor alpha monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis). J Rheumatol 2003;30:2569-2571. 8. Hashkes PJ, Shajrawi I. Sarcoid-related uveitis occurring during etanercept therapy. Clin Exp Rheumatol 2003;21: 645-646. 9. Schmeling H, Horneff G. Etanercept and uveitis in patients with juvenile idiopathic arthritis. Rheumatology (Oxford) 2005;44:1008-1011. 10. Taban M, Dupps WJ, Mandell B, Perez VL. Etanercept (enbrel)-associated inflammatory eye disease: case report and review of the literature. Ocul Immuno Inflam 2006;14: 145-150. 11. Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile idiopathic arthritis. Arthritis Rheum 1997;40: 1202-1209. 12. Lovell DJ, Reiff A, Olcay Y, Schneider R, Nocton J, Stein LD, et al. Long-term safety and efficacy of etanercept in children with polyarticular course juvenile rheumatoid arthritis. Arthritis Rheum 2006;54:1987-1994. 13. Pratsidou-Gertsi R, Vougiouka O, Tsitsami E, Ruperto N, Siamopoulou-Mavridou A, Dracou C, et al. The Greek version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ). Clin Exp Rheumatol 2001;19(Suppl 23):S76-S80. 14. Wallace CA, Ruperto N, Giannini EH for the Childhood Arthritis and Rheumatology Research Alliance (CARRA), The Pediatric Rheumatology International Trials Organization (PRINTO), and the Pediatric Rheumatology Collaborative Study Group (PRCSG). Preliminary criteria for clinical remission for selected categories of juvenile idiopathic arthritis. J Rheumatol 2004;2290-2294. 15. Lahdenne P, Vahasalo P, Honkanen V. Infliximab or etanercept in the treatment of children with refractory
juvenile idiopathic arthritis: an open label study. Ann Rheum Dis 2003;62:245-247. 16. Kanakoudi-Tsakalidou F, Tzimouli V, Pratsidou-Gertsi P, Chronopoulou E, Trachana M. The significance of persistent newly developed autoantibodies in JIA patients under long-term anti-TNF treatment. Cytokine 2008; doi:10.1016/j.cyto.2008.01.007, Volume 42 (p. xxx-xxx) (In Press). 17. Biester S, Deuter C, Michels H, Haefner R, KuemmerleDeschner J, Doycheva D, et al. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol 2007;91:319-324. 18. Tynjälä P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, et al. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology 2008;47:339-344. 19. Lovell DJ, Giannini EH, Reiff A, Jones OY, Schneider R, Olson JC, et al. Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, open-label, extended-treatment trial. Arthritis Rheum 2003;48:218-226. 20. Lovell DJ, Giannini EH. Etanercept therapy in children with juvenile rheumatoid arthritis. Clin Exp Rheumatol 2004;2:522. 21. Horneff G, Schmeling H, Biedermann T, et al. The German etanercept registry for treatment of juvanile idiopathic arthritis. Ann Rheum Dis 2004;63:1638-1644. 22. Quartier P, Taupin P. Bourdeau F, Lemelle I, Pillet P, Bost M, et al. Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 2003;48:1093-1101. 23. Tynjälä P, Lindahl P, Honkanen V, Lahdenne P, Kotaniemi K. Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis 2007;66:548-550. 24. Karlsson JA, Kristensen LE, Kapetanovic MC, Gulfe A, Saxne T, Geborek P. Treatment response to a second or third TNFinhibitor in RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatololy (Oxford) 2008; 47:507-513. 25. Sarah H, Lightman S. Anti-TNF therapies in the management of acute and chronic uveitis. Cytokine 2006; 33:231-237. 26. Saurenmann RK, Levin AV, Feldman BM, Rose JB, Laxer RM, Schneider R, et al. Prevalence, risk factors and outcome of uveitis in juvenile idiopathic arthritis. Arthritis Rheum 2007;56:647-657. 27. Armbrust W, Kamphuis SS, Wolfs TW, Fiselier TJ, Nikkels PG, Kuis W, et al. Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology (Oxford) 2004;43:527-529. 28. Tauber T, Turetz J, Barash J, Avni I, Morad Y. Optic neuritis associated with Etanercept therapy for Juvenile arthritis. J AAROS 2006;10:26-29. 29. Schmeling H, Mathony K, John V, Keysser G, Burdach S, Horneff G. A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study. Ann Rheum Dis 2001;60:410-412. 30. Kietz DA, Pepmueller PH, Moore TL. Theurapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a two year period. Ann Rheum Dis 2002;61: 171-173. ¶·È‰È·ÙÚÈ΋ 2009;72:29-40
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ª. ∆Ú·¯·Ó¿ Î·È Û˘Ó.
31. Lovell DJ. Update on treatment of arthritis in children. New treatments, new goals. Bull NYU Hosp Joint Dis 2006;64:72-76. 32. Ruperto N. 2006 EULAR meeting proceedings. 48-week data from the study of adalimumab in children with juvenile rheumatoid arthritis (JR). Ann Rheum Dis 65:OP007 (Suppl). 33. Gartlehner G, Hansen RA, Jonas BL, Thieda P, Lohr KN. Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence. Clin Rheumatol 2008;27:67-76. 34. Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Emery P, et al. Updated concensus statement on biological agents for the treatment of rheumatic diseases, 2006. Ann Rheum Dis 2006;65(Suppl III):iii2-15.
Paediatriki 2009;72:29-40
35. Russo R∞, Katsicas MM, Zelazco M. Etanercept in systemic juvenile idiopathic arthritis. Clin Exp Rheumatol 2002; 20:723-726. 36. Kimura Y, Pinho P, Walco G, Higgins G, Humell D, Szer I, et al. Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 2005;32:935-942. 37. Moots R, Taggart A, Walker D. Biologic therapy in clinical practice: enthusiasm must be tempered by caution. Rheumatology 2003;42:614-616.
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ORIGINAL ARTICLE
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Obesity prevalence in children aged 8-13 years according to IOTF cutoffs, CDC growth charts and Z-BMI scores N. Mantzouranis, H. Douda, T. Pilianidis, S. Tokmakidis Abstract Background: Few epidemiological studies have compared different classification criteria of childhood obesity. The study on Greek Obesity and Lifestyle (GOAL) investigated the prevalence of childhood obesity in a sample of Greek schoolchildren, comparing three classification criteria. Methods: The study was conducted on 2,056 schoolchildren, aged 8-13 years. The comparisons of obesity were based on the International Obesity Task Force (IOTF) cutoffs, the Centers for Disease Control (CDC) growth charts and body mass index-for-age Z-scores (Z-BMI): median = normal weight, overweight ≥+1SD, obese ≥+2SD. Results: A higher prevalence of obesity and overweight was observed when the CDC growth charts were used [37.6%, 95% CI (35.3-39.9)], while the IOTF cutoffs, revealed slightly lower rates [36.6%, 95% CI (34.3-38.9)]. In relation to both the CDC and IOTF classifications, a significantly lower prevalence was observed when obesity was estimated using Z-BMI [15.6%, 95% CI (13.9-17.3), p<0.05]. ANOVA statistical analysis showed that obesity prevalence was estimated significantly higher in both boys and girls by the CDC and IOTF classification systems than by Z-BMI (p<0.05). Conclusions: When childhood obesity was based on either the IOTF or the CDC criteria, it was found to be the highest ever recorded in a Greek paediatric population, with results nearing the prevalence rates reported for US children. As compared to Z-BMI, the IOTF and CDC classification systems were found to be more appropriate in specifying the prevalence rates of childhood obesity and should, therefore, be used for future public health applications.
Department of Physical Education and Sports Science, Democritus University of Thrace, Komotini 69100, Greece Correspondence: Savvas P. Tokmakidis stokmaki@phyed.duth.gr Department of Physical Education and Sports Science (T.E.F.A.A.) Democritus University of Thrace Komotini 69100, Greece
Key words: Childhood, preadolescence, obesity, classification criteria.
Abbreviations: BMI CDC CI IOTF WHO
Body Mass Index Centers for Disease Control Confidence Interval International Obesity Task Force World Health Organization
Introduction In many developed societies characterized by physical inactivity and over-consumption, obesity has emerged as an undesirable phenomenon. Obviously, excessive fat accumulation in any individual is the result of a long-term positive energy balance and physical inactivity (1). International health-related organizations regard the prevalence of adult and childhood obesity as a global epidemic (2-4). The global prevalence of childhood and adolescent obesity is rising rapidly and could be characterized as a public-health crisis (5). In the USA, the obesity (including overweight) trends more than doubled between 1976 and 2002 (NHAHES & NHANES II, III) and currently one in six children and adolescents are obese (6). In Europe, the highest prevalence trends are observed in the southern Mediterranean countries
(7). In Greece, both representative (8-10) and non representative cross-sectional studies (11-14) have shown the prevalence of childhood and adolescence obesity to be extremely high, leading to the conclusion that Greek children are amongst the most obese in Europe. In epidemiological studies, the evaluation of obesity is based primarily on the use of the practical indirect measure of Body Mass Index (BMI). Two classification methods are recommended for the evaluation of childhood obesity: the USA Centers for Disease Control (CDC) new growth charts (CDC-2000) based on five nationally representative surveys, conducted between 1963 and 1994 (15), and the International Obesity Task Force (IOTF) recommended BMI cutoff points for the definition of overweight and obesity, using anthropometric data collected from six different populations (16). Studies that have compared the above classification methods in the same population found that the BMI reference cutoffs have relatively high specificity, but lower sensitivity (17-18). For this reason, the Multicentre Growth Reference Study (MGRS) of the ¶·È‰È·ÙÚÈ΋ 2009;72:41-45
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tained prior to participation. The GOAL study sampling model was based on the National 2001 census total population distribution and from biostatistical data obtained from the General Secretary of the Hellenic Statistical Service (Figure 1). Official approval for the GOAL study protocol was granted by the Ministry of Education of Greece (Division of Management and Health), the Scientific Research Committee of the Pedagogical Institute of Greece and the ethics committee of the Democritus University of Thrace.
Figure 1. Map of Greece. The dots show the schools in which the Greek Obesity and Lifestyle (GOAL) data were collected.
World Health Organization (WHO) proposed the Z-score curves for BMI-for-age (Z-BMI) for boys and girls from birth to 60 months as an innovative criterion for obesity evaluation (19). Taking into consideration the WHO curves for obesity evaluation based on the BMI-for-age and gender Z-score for the age-group 0-60 months, the present study, the Greek Obesity and Lifestyle (GOAL) study, was undertaken in order to assess the prevalence of childhood obesity according to three different classification criteria, namely the CDC-2000 growth charts, the IOTF cutoffs and the Z-BMI of a reference study population of Greek children aged 8-13 years.
Methods This cohort study was conducted on a stratified representative sample of 2,056 schoolchildren (1,148 boys, 908 girls), aged 10.2±1.3 years. The children evaluated were pupils from 19 randomly selected public primary schools (Figure 1). A whole school class from each of the four grades (3rd to 6th) was surveyed in each primary school. In schools with more than 250 students, one-third of all classes were selected by a random procedure, stratified according to city area and school location. In schools with less than 100 students, measurements were applied to the total school population. Written permission and consent from the subjects and their parents were ob-
Anthropometric data Each child’s age was calculated by subtracting the year, month and date of examination in from the year, month and date of the child’s birth. Body mass was measured to the nearest 100g on a calibrated floor scale (Seca 770), with the child standing in the centre with relaxed arms, wearing no shoes and only light sportswear. Height was measured to the nearest 0.1cm in bare feet, with the head in the Frankfort horizontal plane, using a stadiometer (Seca 240). BMI (kg/m2) was calculated as body mass (kg) divided by the squared height (m2). All the anthropometric measurements were duplicated and performed by the same trained researcher. The comparisons of obesity prevalence in the study population were based on IOTF cutoffs, CDC growth charts and Z-BMI, with 0 equivalent to median = normal weight, overweight ≥+1SD, obese ≥+2SD. Statistical analysis The reliability of the anthropometric measurements of the study was evaluated with the use of autocorrelation analysis (ACF) for different time series data. The syntax file calculates Z-scores for the anthropometric indicator of BMI-forage, based on the GOAL reference population data. The prevalence rates, with a 95% confidence interval (CI), according to the three childhood obesity classification criteria, were compared using the chi square non parametric statistic. Cohen’s Kappa was applied in order to evaluate the classification criteria coefficient of agreement. Statistical significance was set at p <0.05. All statistical analyses were carried out by using the SPSS-PC software, version 16.0 for Windows (SPSS, Inc., Chicago, IL).
Results The Box-Ljung statistics in all lags were significant (p<0.001) and this does not affect the reliability measurements of body mass and height. The anthropometric characteristics of the study children are presented in Table 1. The Z-BMI cutoffs for the boys and girls were
Table 1. Physical and anthropometric characteristics of children who participated in the GOAL* study, according to gender (mean, 95% CI) Total sample (n=2,056) Age (y) Weight (kg) Height (cm) BMI (kg/m2) * Greek Obesity and Lifestyle Paediatriki 2009;72:41-45
Boys (n=1,148) Mean 95% CI 10.2 39.8 142 19.3
10.1-10.3 39.1-40.5 141.9-143.1 19.1-19.6
Girls (n=908) Mean 95% CI 10.2 40 143 19.2
10.1-10.3 39.1-40.7 142.3-143.7 19-19.5
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Table 2. Simplified field table for Z-BMI according to gender, from the reference data of the GOAL* study Boys Z-BMI Age (Year)
Median
+1 SD
+2 SD
17.88 17.95 19.00 19.76 19.31
21.23 21.46 22.73 23.49 22.61
24.60 25.17 26.54 27.30 26.05
Median
+1 SD
+2 SD
17.25 18.11 19.02 19.56 19.32
20.25 21.33 22.83 23.50 23.03
23.34 24.64 26.78 27.50 26.89
8 9 10 11 12 Girls Z-BMI Age (Year) 8 9 10 11 12
the CDC and the IOTF classifications than to Z-BMI (p<0.05) (Figures 2,3). The Cohen’s Kappa measure of agreement between the IOTF and CDC classification criteria was as high as 0.86, while the measure of agreement of both of these obesity classification criteria with the Z-BMI was very low (0.35 and 0.28, respectively).
Discussion Over the past three decades, the prevalence of childhood obesity has been evaluated using different BMI classification criteria. In contrast to a multinational comparative study which showed that the prevalence rates of obesity in pre-pubertal children was the same using the CDC and IOTF criteria (17), the present study found a 1% higher prevalence when obesity was defined according to the CDC growth charts. A cohort study in the USA comparing the prevalence of childhood obesity using different criteria showed that the CDC growth charts give in the same population 5% higher obesity rates in boys in relation to IOTF cutoff references (18). Comparing to the above study rates of obesity, the present study showed a 2.8% higher prevalence of obesity in boys but a 0.9% lower prevalence in girls aged 8-13 years using the CDC criterion, compared to the IOTF cutoffs. In Europe, the prevalence rates of childhood obesity are based mainly on the IOTF definition (20,21). It has recently been demonstrated that BMI has low sensitivity in body fat measurement and estimates the variations from the normal body weight ideal standards (22). For this reason, WHO extended the growth references based on Z-BMI from infants and
* Greek Obesity and Lifestyle, Z-BMI = BMI-for-age score
developed for overweight and obesity classification for the GOAL study reference population (Table 2). Chi-square statistics exhibited that the higher prevalence of childhood obesity (including overweight) was found when the CDC growth charts were used [37.6%, 95% CI (35.3-39.9)]. The prevalence of obesity as estimated according to the IOTF cutoffs recorded 1% lower rates [36.6%, 95% CI (34.338.9)]. Significantly lower prevalence was recorded when obesity was estimated by Z-BMI [15.6%, 95% CI (13.9-17.3)], compared to the CDC (¯2=2.32, df =4, p<0.05) and IOTF (¯2=1.28, df=4, p<0.05) classifications. Adjusted by gender, obesity prevalence was significantly higher in boys and girls according to both
21.4
CDC
18 .7
25.2
IOTF
11.2 *
GOALS
0
#
5
5
Overweight
12 .1
10
15
20
25
30
35
40
45
Obesity
* p<0.05 vs CDC & IOTF overweight #
p<0.05 vs obesity
Figure 2. Prevalence (%) of overweight and obesity in boys, according to the three BMI-for-age classification criteria: CDC, IOTF and Z-BMI (GOAL). ¶·È‰È·ÙÚÈ΋ 2009;72:41-45
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12.9
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CDC
25.5
IOTF
GOALS
11.2 * 0
3.8
5 Overweight
10.3
10
#
15
20
25
30
35
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Obesity
* p<0.05 vs CDC & IOTF overweight #
p<0.05 vs obesity
Figure 3. Prevalence (%) of overweight and obesity in girls, according to the three BMI-for-age classification criteria: CDC, IOTF and Z-BMI (GOAL).
toddlers to cover children and adolescents aged 5-19 years (23). The present study is one of the first studies to compare the CDC and IOTF obesity eva-luation criteria with the Z-BMI in primary schoolchildren. Comparison with earlier representative population studies in Greece using the IOTF criteria shows that the prevalence of childhood obesity in the GOAL study, based on both the IOTF and the CDC classifications, is the highest ever recorded in Greece and approaches the obesity prevalence rates reported in the USA. However, the prevalence of overweight and obesity recorded in the study population using Z-BMI was even lower than the WHO-HBSC study (IOTF-CDC criteria), which was conducted on 11.5 year-old preadolescents, based on self-reported anthropometric data [(overweight: HBSCIOTF 15.2% - HBSCCDC 15.5% vs GOALBMI-for-age Z-scores 11.2%), (obesity: HBSCIOTF 1.5% - HBSCCDC 3.4% vs GOALBMI- for-age Z-scores 15.6%)]. In conclusion, the findings of the present study are in accordance with recent epidemiological studies, confirming that childhood obesity in Greece has increased rapidly in recent years. The comparison of three different classification systems showed that the Z-BMI did not appropriately specify childhood obesity in primary schoolchildren, in contrast with the IOTF and CDC classifications, and should not be used for public health applications. Therefore, a common obesity evaluation standard must be established for widespread use in the assessment of school-age children.
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demic. World Health Organization. Technical Report Ser no. 894, 2000. (ISBN Number for the Obesity TRS Is 92 4 120894 5). 3. International Obesity Task Force with the European Childhood Obesity Group. Obesity in Europe. 2002, Technical Report, Copenhagen, IOTF. 4. WHO European Ministerial Conference on Counteracting Obesity. Diet and Physical Activity for health. The challenge of obesity in the WHO European Region and the strategies for response. WHO, Istanbul, Turkey, 15-17 November 2006. 5. Lobstein T, Baur L, Uauy R for the IASO International Obesity Task Force. Obesity in children and young people: a crisis in public health. Obes Rev 2004;5(1 Suppl): S4-85. 6. Baskin ML, Ard J, Franklin F, Alison DB. National Prevalence of Obesity. Prevalence of obesity in the United States. Obes Rev 2005;6:5-7. 7. Lobstein TJ, Flelut M-L. Prevalence of overweight children in Europe. Obes Rev 2003;4:195-200. 8. Kapantais E, Haralambidis V, Tzotzas T, Mortoglou A, Bakatselos S, Kaklamanou M, et al. First National Epidemiological Large Survey on the Prevalence of Childhood and Adolescent Obesity in Greece. Int J Obes 2004; 28(1 Suppl):S71. 9. Karayiannis D, Yannakoulia M, Terzidou M, Sidossis LS, Kokkevi A. Prevalence of overweight and obesity in Greek school-aged children and adolescents. Eur J Clin Nutr 2003;57(9):1189-1192. 10. Mantzouranis N, Douda H, Pilianidis T, Tokmakidis S. Comparison of IOTF cutoffs, CDC growth charts and National growth curves in the prevalence of childhood obesity. The Greek Obesity and Lifestyle Study. Obes Rev 2007;8(3 Suppl):S27. 11. Mamalakis G, Kafatos A. Prevalence of obesity in Greece. Int J Obes 1996;20:488-92. 12. Krassas GE, Tzotzas T, Tsametis C, Konstandinidis T. Prevalence and Trends in Overweight among Children and Adolescents in Thessaloniki, Greece. J Ped Endocr & Metab 2001;14:1319-1326.
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13. Tokmakidis PS, Christodoulos A, Mantzouranis N. Validity of Self-Reported Height and Body Mass in Greek Elementary and High School Students. J Adoles Health 2007;40:305-310. 14. Chiotis D, Krikos X, Tsiftis G, Hatzisymeaon M, ManiatiChristidi M, Dacou-Voutedaki A. Body mass index and prevalence of obesity in subjects of Hellenic origin aged 0-18 years, living in the Athens area. Ann Clin Pediatr University Atheniensis 2004;51:139-154. 15. Kuczmarski RJ, Odgen CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al. CDC growth charts: United States. Advances Data from Vital and Health Statistics 2000; No 314. Hyattsville, MA: National Center for Health Statistics. 16. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000;320:1-6. 17. Wang Y, Wang JQ. A comparison of international references of the assessment of child and adolescents overweight and obesity in different populations. Eur J Clin Nutrition 2002;56:973-982. 18. Flegal KM, Ogden CL, Wei, Kuczmarski RL, Johnson CL. Prevalence of overweight in US children: comparison of
US growth charts from the Centers for Disease Control and Prevention with other reference values for body mass index. Am J Clin Nutr 2001;73:1086-1093. 19. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr 2006;95(450 Suppl):S76-85. 20. Kosti RJ, Panagiotakos DB. The epidemic of obesity in children and adolescents in the world. Cent Eur J Public Health 2006;14:151-159. 21. Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatric Obes 2006;1:11-25. 22. Reilly JJ, Dorosty AR, Emmett PM. The ALSPAC Study Team. The identification of the obese child: adequacy of the body mass index for clinical practice and epidemiology. Int J Obes Relat Metab Disord 2000;24:1623-1627. 23. De Onis M, Onyango WA, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bulletin of the World Health Organization 2007;85:660-667.
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ORIGINAL ARTICLE
ÃÚ‹ÛË Î·È Î·Ù¿¯ÚËÛË ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ Û ÊÔÈÙËÙ¤˜ ·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜ ∆Ì‹Ì· ¶ÚÔÛ¯ÔÏÈ΋˜ ∞ÁˆÁ‹˜, ™¯ÔÏ‹ ∂·ÁÁÂÏÌ¿ÙˆÓ ÀÁ›·˜ Î·È ¶ÚfiÓÔÈ·˜, ∞ÓÒÙ·ÙÔ ∆¯ÓÔÏÔÁÈÎfi ∂Î·È‰Â˘ÙÈÎfi ÿ‰Ú˘Ì· ∞ı‹Ó·˜ AÏÏËÏÔÁÚ·Ê›·: ™Ù¤ÏÈÔ˜ ∞ÓÙˆÓÈ¿‰Ë˜ prdrsant@otenet.gr ∏Ú·ÎÏ›ÙÔ˘ 4, ∫ÔψӿÎÈ 106 73 ∞ı‹Ó·
™. ∞ÓÙˆÓÈ¿‰Ë˜, Ã. °È·‚Ú‹, ∂. ¶··Ì·Î·Ú›Ô˘, ∫. ™Ù·‡ÚÔ˘, ª. ∑¤Ú‚·, ∂. ¢ÈÔÓ˘ÛÔÔ‡ÏÔ˘, ∂. ª·ÎÚÔÁΛη, µ. ™·ÏˆÓ›‰Ë˜ ¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: ∏ ¯Ú‹ÛË Î·È Ë Î·Ù¿¯ÚËÛË ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ, fiˆ˜ ÙÔ ·ÏÎÔfiÏ, Ô Î·Ófi˜ Î·È Ù· Ó·ÚΈÙÈο, ÌÔÚ› Ó· ‚Ï¿„Ô˘Ó ÛÔ‚·Ú¿ ÙËÓ ˘Á›·. ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ë ‰ÈÂÚ‡ÓËÛË Ù˘ ¯Ú‹Û˘ Î·È Ù˘ ηٿ¯ÚËÛ˘ ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ ·fi Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ ÊÔÈÙËÙ¤˜ ·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜. ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ™ÙË ‰È¿ÚÎÂÈ· ÂÓfi˜ ¯ÚfiÓÔ˘, ÌÂÏÂÙ‹Û·ÌÂ, ‚¿ÛÂÈ ÚˆÙÔÎfiÏÏÔ˘ Ì ÎÏÂÈÛÙfi ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ, 954 ÊÔÈÙËÙ¤˜ Û¯ÔÏÒÓ Â·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜ ÙÔ˘ ∞ÓÒÙ·ÙÔ˘ ∆¯ÓÔÏÔÁÈÎÔ‡ ∂Î·È‰Â˘ÙÈÎÔ‡ π‰Ú‡Ì·ÙÔ˜ ∞ı‹Ó·˜. ∞ÔÙÂϤÛÌ·Ù·: ∏ ËÏÈΛ· Î˘Ì·ÈÓfiÙ·Ó ÌÂٷ͇ 17-22 ÂÙÒÓ, 910 (95%) ‹Ù·Ó ŒÏÏËÓ˜, 522 (55%) ·fi ÙËÓ ∞ı‹Ó·, 945 (99%) ›¯·Ó Ê˘ÛÈÎÔ‡˜ ÁÔÓ›˜, 55 (6%) ›¯·Ó ‰È·˙¢Á̤ÓÔ˘˜ ÁÔÓ›˜. √ÈÓÔÓÂ˘Ì·ÙÒ‰Ë ‰ÂÓ Â›¯·Ó ÈÂÈ ÔÙ¤ 227 (24%), 725 (76%) ›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ, 388 (54%) ¤ÈÓ·Ó ÂÚÈÛÙ·Ûȷο, 196 (27%) ¤ÈÓ·Ó Ì›· ÊÔÚ¿ ÙËÓ Â‚‰ÔÌ¿‰·, 119 (16%) ¤ÈÓ·Ó 2-3 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·, 17 (2%) ¤ÈÓ·Ó Î¿ı ̤ڷ, 324 (45%) ¤ÈÓ·Ó Û˘Ó‹ıˆ˜ ÂÏ·ÊÚÈ¿ ÔÙ¿, 223 (31%) ¤ÈÓ·Ó ‚·ÚÈ¿ ÔÙ¿, 536 (74%) ¤ÈÓ·Ó 1-2 ÔÙ‹ÚÈ· οı ÊÔÚ¿, 147 (20%) ¤ÈÓ·Ó 3-5 ÔÙ‹ÚÈ· Î·È 31 (4%) ¤ÈÓ·Ó ÂÚÈÛÛfiÙÂÚ·, 339 (47%) ¤ÈÓ·Ó Û˘Ó‹ıˆ˜ Ì ·Ú¤·, 505 (81%) ¤ÈÓ·Ó Û ʿÛË ‰È·ÛΤ‰·Û˘, ‰È·ÎÔÒÓ. ª¤ıË ·Ó¤ÊÂÚ·Ó 400 (55%), Û 113 (18%) ˘‹ÚÍ ÌË ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓË ÛÂÍÔ˘·ÏÈ΋ Ú¿ÍË, Û 36 (5%) ηÎÔÔ›ËÛË, 848 (89%) ‰ÂÓ Ô‰ËÁÔ‡Û·Ó ˘fi ÙËÓ Â‹ÚÂÈ· ÔÈÓÔÓ‡̷ÙÔ˜. √È 629 (66%) ‰ÂÓ Î¿ÓÈ˙·Ó, 322 (34%) οÓÈ˙·Ó, 250 (78%) οÓÈ˙·Ó Û˘ÛÙËÌ·ÙÈο. √È 125 (39%) ·Ó¤ÊÂÚ·Ó ÙË ‰‡Ó·ÌË Ù˘ Û˘Ó‹ıÂÈ·˜ ˆ˜ ·ÈÙ›·, ÂÓÒ 154 (48%) ·Ó¤ÊÂÚ·Ó ÙËÓ ·fiÏ·˘ÛË ˆ˜ ·ÔÙ¤ÏÂÛÌ·. ŸÏÔÈ ÁÓÒÚÈ˙·Ó ÙȘ ‚Ï·‚ÂÚ¤˜ Û˘Ó¤ÂȘ ÙÔ˘ ηӛÛÌ·ÙÔ˜ Î·È Â›¯·Ó ·Ú΋ ÂÓË̤ڈÛË 244 (76%). ∆¤ÏÔ˜, 50 (5%) ‹Ù·Ó ¯Ú‹ÛÙ˜, ÚÔ˚fiÓÙˆÓ Î¿ÓÓ·‚˘ 32 (64%), ÎÔη˝Ó˘ 12 (24%), ¯·ÈÒÓ 4 (8%), ËÚˆ›Ó˘ 2 (4%), 19 (38%) ›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ ÌfiÓÔ 1-2 ÊÔÚ¤˜, 17 (34%) ‹Ù·Ó Û˘ÛÙËÌ·ÙÈÎÔ› ¯Ú‹ÛÙ˜. ªÔÏÔÓfiÙÈ 47 (94%) ÁÓÒÚÈ˙·Ó ÙȘ ÂÈÙÒÛÂȘ, ÌfiÓÔ 16 (32%) ÂÈı˘ÌÔ‡Û·Ó Ó· ‰È·Îfi„Ô˘Ó. ™˘ÌÂÚ¿ÛÌ·Ù·: ∆Ô Û˘ÁÎÚÈÙÈο ÌÈÎÚfiÙÂÚÔ ÔÛÔÛÙfi ÙˆÓ Î·ÓÈÛÙÒÓ Î·Ù¿ ¿Û· Èı·ÓfiÙËÙ· ÔÊ›ÏÂÙ·È ÛÙËÓ ÂÈÙ˘¯›· Ù˘ ·ÓÙÈηÓÈÛÙÈ΋˜ ÂÎÛÙÚ·Ù›·˜, ·fi ÎÚ·ÙÈÎÔ‡˜ Î·È ¿ÏÏÔ˘˜ ÊÔÚ›˜. ∆Ô ›‰ÈÔ Ê·›ÓÂÙ·È Ó· ÈÛ¯‡ÂÈ Î·È ÛÙÔ ı¤Ì· Ù˘ Ô‰‹ÁËÛ˘ ÌÂÙ¿ ·fi ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜. ¶ÈÛÙ‡ԢÌ fiÙÈ Ú¤ÂÈ Ó· ÂÓÙ·ıÔ‡Ó ÔÈ ÚÔÛ¿ıÂȘ ·fi ÙËÓ ÔÈÎÔÁ¤ÓÂÈ·, ÙÔ Û¯ÔÏÂ›Ô Î·È fiÏÔ˘˜ ÙÔ˘˜ ÊÔÚ›˜, Ô‡Ùˆ˜ ÒÛÙ ӷ ÂÈÙ¢¯ıÔ‡Ó ÔÈ ÛÙfi¯ÔÈ.
§¤ÍÂȘ ÎÏÂȉȿ: ÃÚ‹ÛË-ηٿ¯ÚËÛË ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ, ÊÔÈÙËÙ¤˜.
Use and abuse of substances by young adult students of the health professions Department of Early Childhood Education, Faculty of Health and Caring Professions, Technological Educational Institute of Athens Correspondence: Stelios Antoniadis prdrsant@otenet.gr 4, Iraklitou St., Kolonaki 106 73 Athens Greece
Paediatriki 2009;72:46-50
S. Antoniadis, C. Giavri, E. Papamacariou, K. Stavrou, M. Zerva., E. Dionyssopoulou, E. Makrogkika, V. Salonidis Abstract Introduction: Substance abuse can seriously damage health. The objective of this study was to investigate the use and abuse of substances by students of the health professions. Methods: During the course of two semesters, 954 students of the Technological Educational Institute (TEI) of Athens were studied, according to a special protocol using a closed questionnaire. Results: The age of the participants was 17-22 years. Regarding alcohol use, 227 (24%) students had never tried alcohol, 725 (76%) had tried once, 388 (54%) occasionally, 196 (27%) once a week, 119 (16%) 2-3 times weekly, 17 (2%) every day. The type of alcohol was: light drinks 324 (45%), heavy drinks 223 (31%), and the amount was: 1-2 drinks each time 536 (74%), 3-5 drinks 147 (20%), more than 5 drinks 31 (4%). The circumstances of drinking were: during parties 339 (47%) and on vacations 505 (81%); 400 (55%) reported getting drunk, 113 (18%) having unplanned sexual activity and 36 (5%) had been assaulted when drinking. Not driving after drinking was practiced by 848 (89%), and no accidents were reported. Tobacco had never been used by 629 (66%), 322 (34%) were smokers, 250 (78%) were
Pediatric Jan-Feb 09
16-03-09
14:56
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47
∂Í·ÚÙËÛÈÔÁfiÓ˜ Ô˘Û›Â˜ Û ÊÔÈÙËÙ¤˜ ·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜
regular smokers; among smokers, 125 (39%) smoked because of the force of habit and 154 (48%) for the enjoyment, while 244 (76%) reported being aware of the harmful effects. Among the students, 50 (5%) were drug users, specifically: marijuana 32 (64%), cocaine 12 (24%), club drugs 4 (8%), heroin 2 (4%). Among the drug users, 19 (38%) took drugs occasionally, and 17 (34%) daily; 47 (94%) knew the consequences, 16 (32%) were motivated to quit. Conclusions: The relatively small number of smokers is most probably due to the effectiveness of the smoking cessation programs. The success of preventing driving after alcohol use is likely to be due to the information strategies that have been used. The researchers believe that students’ families and the community should try harder in order to meet the targets for reduction of substance abuse.
Key words: Substance abuse, students, health professions studies.
∂ÈÛ·ÁˆÁ‹ ∏ ¯Ú‹ÛË Î·È Î·Ù¿¯ÚËÛË ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ, fiˆ˜ ÙÔ ·ÏÎÔfiÏ, Ô Î·Ófi˜ Î·È Ù· ¿ÏÏ· ÂÍ·ÚÙËÛÈÔÁfiÓ· (ÚÔ˚fiÓÙ· οÓÓ·‚˘, ÎÔη˝ÓË, ËÚˆ›ÓË, ¯¿È· Î.Ù.Ï.), Â›Ó·È ÁÓˆÛÙfi fiÙÈ ÌÔÚ› Ó· ¤¯Ô˘Ó ÛÔ‚·Ú¤˜ ÂÈÙÒÛÂȘ ÛÙËÓ ˘Á›·. ∏ ¤Ó·ÚÍË Ù˘ ¯Ú‹Û˘ ÔÈÓÔÓ‡̷ÙÔ˜ ·fi ÙËÓ ÂÊË‚È΋ ‹ ÙËÓ ÚÒÙË Ó·ÓÈ΋ ËÏÈΛ·, ÛÂ Û˘Ó¿ÚÙËÛË Ì ÙÔ Â›‰Ô˜ ÙÔ˘ ÔÙÔ‡ ·ÏÏ¿ Î·È ÙË Û˘¯ÓfiÙËÙ· ηٷӿψÛ˘, ¤¯ÂÈ È‰È·›ÙÂÚË ÛËÌ·Û›·. ∆Ô Î¿ÓÈÛÌ· Â›Ó·È Ôχ ηϿ ÁÓˆÛÙfi fiÙÈ ÌÔÚ› Ó· ‚Ï¿„ÂÈ ÛÔ‚·Ú¿ ÙËÓ ˘Á›·, ÂÂȉ‹ fï˜ ÔÈ ‚Ï¿‚˜ ‰ÂÓ Â›Ó·È ÔÚ·Ù¤˜ ÛÙȘ ËÏÈ˘ Ô˘ ÔÈ ¿ÓıÚˆÔÈ Â›Ó·È ÊÔÈÙËÙ¤˜, ÔÏÏÔ› ‰˘ÛÎÔχÔÓÙ·È Ó· ÈÛÙ¤„Ô˘Ó ·˘Ù¿ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ȷÙÚÈο ¿ÚıÚ·, ·ÏÏ¿ Î·È ÛÙȘ ÂÊËÌÂÚ›‰Â˜, Ù· ÂÚÈÔ‰Èο, ηıÒ˜ Î·È Ù· ¿ÏÏ· ̤۷ Ì·˙È΋˜ ÂÓË̤ڈÛ˘. ∞ÓÙ›ıÂÙ·, Ë ¯Ú‹ÛË ¿ÏÏˆÓ ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ ‰ËÌÈÔ˘ÚÁ› ۈ̷ÙÈΤ˜, „˘¯ÔÏÔÁÈΤ˜, ηıÒ˜ Î·È ÎÔÈÓˆÓÈΤ˜ ÂÈÏÔΤ˜, ÔÈ Ôԛ˜ οÓÔ˘Ó ÙËÓ ÂÌÊ¿ÓÈÛ‹ ÙÔ˘˜ Ôχ ÁÚ‹ÁÔÚ·. §fiÁˆ ÙÔ˘ È·ÙÚÈÎÔ‡ ·ÏÏ¿ Î·È ÙÔ˘ ÎÔÈÓˆÓÈÎÔ‡ ÙÔ˘˜ ÂӉȷʤÚÔÓÙÔ˜, Ù· ·Ú·¿Óˆ ı· Ú¤ÂÈ Ó· ·Ó·ÁÓˆÚ›˙ÔÓÙ·È ¤ÁηÈÚ· Î·È Ó· ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È ˆ˜ ÛÔ‚·Ú¿ ÚÔ‚Ï‹Ì·Ù· ‰ËÌfiÛÈ·˜ ˘Á›·˜ (1,2). ™ÎÔfi˜ Ù˘ ÂÚÁ·Û›·˜ Ì·˜ ‹Ù·Ó Ë ‰ÈÂÚ‡ÓËÛË Ù˘ ¯Ú‹Û˘ Î·È Ù˘ ηٿ¯ÚËÛ˘ ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ ·fi Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ ÊÔÈÙËÙ¤˜ ·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜. ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ™ÙË ‰È¿ÚÎÂÈ· ÂÓfi˜ ¯ÚfiÓÔ˘, ÌÂÏÂÙ‹Û·ÌÂ, ‚¿ÛÂÈ ÚˆÙÔÎfiÏÏÔ˘ Ì ÎÏÂÈÛÙfi ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ, 954 ÊÔÈÙËÙ¤˜ Û¯ÔÏÒÓ Â·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜ (ÓÔÛËÏ¢ÙÈ΋, Ì·È¢ÙÈ΋, Ê˘ÛÈÔıÂڷ›·, ÂÚÁÔıÂڷ›·, ‚ÚÂÊÔÓËÈÔÎÔÌ›·, ÂÈÛÎÂÙÒÓ ˘Á›·˜), ÙÔ˘ ∞ÓÒÙ·ÙÔ˘ ∆¯ÓÔÏÔÁÈÎÔ‡ ∂Î·È‰Â˘ÙÈÎÔ‡ π‰Ú‡Ì·ÙÔ˜ ∞ı‹Ó·˜. ∆· ·ÔÙÂϤÛÌ·Ù· Ù˘ ¤Ú¢ӷ˜ ÚԤ΢„·Ó ̤ۈ ·Ó¿Ï˘Û˘ ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ÙˆÓ ÂÚˆÙËÌ·ÙÔÏÔÁ›ˆÓ Û ËÏÂÎÙÚÔÓÈÎfi ˘ÔÏÔÁÈÛÙ‹, Ì ÙË ‚Ô‹ıÂÈ· ÙÔ˘ ÚÔÁÚ¿ÌÌ·ÙÔ˜ SPSS.
∞ÔÙÂϤÛÌ·Ù· ∏ ËÏÈΛ· Î˘Ì·ÈÓfiÙ·Ó ÌÂٷ͇ 17-22 ÂÙÒÓ, Ì ̤ÛË ËÏÈΛ· Ù· 19,5 ¯ÚfiÓÈ· (ÂÎÙfi˜ ·fi ÌÈ· ÌÈÎÚ‹ ÔÌ¿‰· ÊÔÈÙËÙÒÓ ·ÚÂÏıfiÓÙˆÓ ÂÙÒÓ, Ô˘ ›¯·Ó ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ·). ∞fi ·˘ÙÔ‡˜, ÔÈ 522 (55%) ηٿÁÔÓÙ·Ó ·fi ÙËÓ ∞ı‹Ó· Î·È ÔÈ 425 (45%) ·fi ÙËÓ ÂÚÈʤÚÂÈ·, 814 (85%) ‰‹ÏˆÛ·Ó ˆ˜ ÙfiÔ ÌfiÓÈÌ˘ ηÙÔÈΛ·˜ ÙËÓ ∞ı‹Ó· Î·È 135 (14%) ·ÛÙÈο Î·È ÂÚÈ·ÛÙÈο ΤÓÙÚ· Ù˘ ÂÚÈʤÚÂÈ·˜. ∞fi ÙÔ Û‡ÓÔÏÔ ÙˆÓ ÊÔÈÙËÙÒÓ, 910 (95%) ‹Ù·Ó ŒÏÏËÓ˜ Î·È 38 (4%) ·ÏÏÔ‰·Ô›, (6 ‰ÂÓ ·¿ÓÙËÛ·Ó). ™Â fiÙÈ ·ÊÔÚ¿ ÙÔ ÌÔÚʈÙÈÎfi Â›Â‰Ô ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘˜, 417 (44%) ‹Ù·Ó ·fiÊÔÈÙÔÈ ‰Â˘ÙÂÚÔ‚¿ıÌÈ·˜ Âη›‰Â˘Û˘, 360 (38%) ÙÚÈÙÔ‚¿ıÌÈ·˜, 158 (17%) ÚˆÙÔ‚¿ıÌÈ·˜, ÂÓÒ 945 (99%) ‹Ù·Ó Ê˘ÛÈÎÔ› ÁÔÓ›˜, 55 (6%) ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ‹Ù·Ó ‰È·˙¢Á̤ÓÔÈ. √È 875 (92%) ÊÔÈÙËÙ¤˜ ›¯·Ó ¤Ó· ‹ ‰‡Ô ·‰¤ÏÊÈ·, ÂÓÒ 113 (12%) ÂÚÈÛÛfiÙÂÚ·, 927 (97%) ‹Ù·Ó ·fiÊÔÈÙÔÈ ‰ËÌfiÛÈ·˜ ‰Â˘ÙÂÚÔ‚¿ıÌÈ·˜ Âη›‰Â˘Û˘ Î·È 21 (2%) ȉȈÙÈ΋˜, 385 (40%) ·Û¯ÔÏÔ‡ÓÙ·Ó Ì ÙÔÓ ·ıÏËÙÈÛÌfi, 226 (24%) Ì ÙË ÌÔ˘ÛÈ΋, 101 (11%) ·Ó¤ÊÂÚ·Ó ÂӉȷʤÚÔÓ ÁÈ· ÙȘ Ù¤¯Ó˜, ÂÓÒ 242 (22%) ‰ÂÓ ·¿ÓÙËÛ·Ó. ™Â fiÙÈ ·ÊÔÚ¿ ÙË ¯Ú‹ÛË ÔÈÓÔÓÂ˘Ì·Ùˆ‰ÒÓ ÔÙÒÓ, 725 ÊÔÈÙËÙ¤˜ (76%) ›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ ¤ÛÙˆ Î·È Ì›· ÊÔÚ¿ οÔÈÔ ÔÈÓÔÓÂ˘Ì·Ù҉˜ ÔÙfi, ÂÓÒ 227 (24%) ‰ÂÓ Â›¯·Ó ÈÂÈ ÔÙ¤. ∏ ÚÒÙË Â·Ê‹ ÙÔ˘˜ Ì ÙÔ ÔÙfi ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ÍÂÎÈÓÔ‡Û ÌÂÙ¿ ·fi ÙËÓ ËÏÈΛ· ÙˆÓ 15 ¯ÚfiÓˆÓ [499 (69%)]. √È ÂÚÈÛÛfiÙÂÚÔÈ ·fi ·˘ÙÔ‡˜ [388 (54%)] Î·Ù·Ó¿ÏˆÓ·Ó ·ÏÎÔfiÏ ÂÚÈÛÙ·Ûȷο, ÔÈ 196 (27%) Ì›· ÊÔÚ¿ ÙËÓ Â‚‰ÔÌ¿‰·, 119 (16%) 2-3 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·, 17 (2%) οı ̤ڷ. √È 324 (45%) Î·Ù·Ó¿ÏˆÓ·Ó Û˘Ó‹ıˆ˜ ÂÏ·ÊÚÈ¿ ÔÙ¿, fiˆ˜ ̛ڷ, ÎÚ·Û› (ÂÚÈÂÎÙÈÎfiÙËÙ˜ ÔÈÓÔÓ‡̷ÙÔ˜ 5-14%) Î·È ÔÈ 223 (31%) ‚·ÚÈ¿ ÔÙ¿ Ì ˘„ËÏ‹ ÂÚÈÂÎÙÈÎfiÙËÙ· Û ÔÈÓfiÓÂ˘Ì·, fiˆ˜ Ô˘›ÛÎÈ, ‚fiÙη, Ù˙ÈÓ ¶·È‰È·ÙÚÈ΋ 2009;72:46-50
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·48
48
™. ∞ÓÙˆÓÈ¿‰Ë˜ Î·È Û˘Ó.
Î.Ù.Ï. (ÂÚÈÂÎÙÈÎfiÙËÙ· ÔÈÓÔÓ‡̷ÙÔ˜ 40%), ÂÓÒ 178 (24%) ‰ÂÓ ·¿ÓÙËÛ·Ó. ŸÛÔÓ ·ÊÔÚ¿ ÙËÓ ÔÛfiÙËÙ·, 536 (74%) ¤ÈÓ·Ó Î¿ı ÊÔÚ¿ 1-2 ÔÙ‹ÚÈ·, 147 (20%) 3-5 ÔÙ‹ÚÈ· Î·È 31 (4%) ÂÚÈÛÛfiÙÂÚ· ·fi 5. ∏ ¯Ú‹ÛË ÙÔ˘ ÔÈÓÔÓÂ˘Ì·ÙÒ‰Ô˘˜ ÁÈÓfiÙ·Ó Û˘¯ÓfiÙÂÚ· Ì ·Ú¤· [339 (47%)], Û˘Ó‹ıˆ˜ Û ʿÛË ‰È·ÛΤ‰·Û˘ Î·È ‰È·ÎÔÒÓ [505 (81%)], ÂÓÒ 63 (8%) ÊÔÈÙËÙ¤˜ ‰ÂÓ ı¤ÏËÛ·Ó Ó· ··ÓÙ‹ÛÔ˘Ó. ¶·ÚfiÏÔ Ô˘ ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ‰ÂÓ ¤ÈÓ·Ó ÌfiÓÔÈ ÙÔ˘˜, 547 (75%) ‰‹ÏˆÛ·Ó fiÙÈ ‰ÂÓ ÙÔ˘˜ ·Ú¤Û˘Ú·Ó ÔÈ Û˘Ó·Ó·ÛÙÚÔʤ˜ ÙÔ˘˜. ™Â fiÙÈ ·ÊÔÚ¿ ÙȘ ÂÈÙÒÛÂȘ Ù˘ ˘ÂÚ‚ÔÏÈ΋˜ ηٷӿψÛ˘, 400 (55%) ·Ó¤ÊÂÚ·Ó Ì¤ıË Ì ·ÓÂÈı‡ÌËÙ· ·ÎfiÏÔ˘ı·: ÙË ˙¿ÏË [260 (36%)], ÙËÓ ÎÂÊ·Ï·ÏÁ›· [196 (27%)], ÙÔÓ ÂÌÂÙfi [156 (22%)] ‹ ÛÔ‚·ÚfiÙÂÚ˜ ηٷÛÙ¿ÛÂȘ [7 (1%)]. ™Â 113 (18%) ˘‹ÚÍ ÌË ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓË ÛÂÍÔ˘·ÏÈ΋ Ú¿ÍË Î·È Û 36 (5%) ηÎÔÔ›ËÛË ·fi ¿ÏÏÔ ¿ÙÔÌÔ. ™ÙË Û˘ÓÙÚÈÙÈ΋ ÙÔ˘˜ ÏÂÈÔ„ËÊ›· [848 (89%)] ·Ó¤ÊÂÚ·Ó fiÙÈ ‰ÂÓ Ô‰ËÁÔ‡Û·Ó ˘fi ÙËÓ Â‹ÚÂÈ· ÔÈÓÔÓ‡̷ÙÔ˜ Î·È ‰ÂÓ Â›¯·Ó ÙÚÔ¯·›Ô ·Ù‡¯ËÌ·. ™ÙË Û‡ÁÎÚÈÛË ÙˆÓ Û˘ÓËıÂÈÒÓ ÙˆÓ ÊÔÈÙËÙÒÓ Ì ·˘Ù¤˜ ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘˜, ‰ÂÓ ˘‹ÚÍ·Ó ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜, ·ÊÔ‡ 64% (467) ÙˆÓ ÁÔÓ¤ˆÓ ¤Î·Ó·Ó ۯ‰fiÓ ÂÚÈÛÙ·Ûȷ΋ ¯Ú‹ÛË ÂÏ·ÊÚÒÓ ÔÈÓÔÓÂ˘Ì·Ùˆ‰ÒÓ ÔÙÒÓ, ÂÓÒ Û 118 (25%) ÂÚˆÙËÌ·ÙÔÏfiÁÈ· ‰ÂÓ ˘‹Ú¯Â ·¿ÓÙËÛË. ø˜ ÚÔ˜ ÙÔ Î¿ÓÈÛÌ·, Ê¿ÓËΠfiÙÈ ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ [629 (66%)] ‰ÂÓ ¤Î·Ó·Ó ¯Ú‹ÛË Î·ÓÔ‡, Ô‡ÙÂ Î·È Â›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ ÛÙÔ ·ÚÂÏıfiÓ. ∞fi ·˘ÙÔ‡˜ fï˜ Ô˘ ηӛ˙Ô˘Ó [322 (34%)], ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ [250 (78%)] ·Ó¤ÊÂÚ·Ó fiÙÈ Â›Ó·È Û˘ÛÙËÌ·ÙÈÎÔ› ηÓÈÛÙ¤˜, Ì ËÌÂÚ‹ÛÈ· ηٷӿψÛË ÂÚÈÛÛfiÙÂÚˆÓ ÙˆÓ 10 ÙÛÈÁ¿ÚˆÓ (51%), ÂÓÒ 65 (20%) ‰‹ÏˆÛ·Ó fiÙÈ Î¿ÓÈ˙·Ó ÂÚÈÛÙ·Ûȷο. ø˜ ÚÒÙË ËÏÈΛ· ¯Ú‹Û˘ ÙÛÈÁ¿ÚˆÓ, ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi [277 (86%)] ·Ó¤ÊÂÚ fiÙÈ ¿Ú¯ÈÛ ÙÔ Î¿ÓÈÛÌ· ÌÂÙ¿ ÙËÓ ËÏÈΛ· ÙˆÓ 15 ¯ÚfiÓˆÓ, 201 (62%) ›ÛÙ¢·Ó fiÙÈ ‰ÂÓ Â›¯·Ó ·Ú·ÎÈÓËı› ·fi ÙȘ Û˘Ó·Ó·ÛÙÚÔʤ˜ ÙÔ˘˜, ·Ó Î·È ÛÙËÓ ·Ú¤· ÙÔ˘˜ ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ [262 (81%)] οÓÈ˙·Ó. ∂›Û˘, Ê¿ÓËΠfiÙÈ Û˘ÓËı¤ÛÙÂÚ· ‰ÂÓ Û˘Ó‰‡·˙·Ó ÙÔ Î¿ÓÈÛÌ· Ì ·ÏÎÔfiÏË ‹ ¿ÏϘ Ô˘Û›Â˜ [177 (55%)], ÌÔÏÔÓfiÙÈ 110 (34%) ¤Î·Ó·Ó Ù·˘Ùfi¯ÚÔÓË ¯Ú‹ÛË ·ÏÎÔfiÏ Î·È 11 (3%) ¿ÏÏˆÓ Ô˘ÛÈÒÓ. ø˜ ·ÈÙ›· ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ·Ó¤ÊÂÚ·Ó ÙË ‰‡Ó·ÌË Ù˘ Û˘Ó‹ıÂÈ·˜ [125 (39%)], ÂÓÒ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÌfiÓÔ ÔÈ 154 (48%) ·Ó¤ÊÂÚ·Ó ÙËÓ ·fiÏ·˘ÛË - ÔÈ ˘fiÏÔÈÔÈ ‰ÂÓ ·¿ÓÙËÛ·Ó. ™ÙË Û‡ÁÎÚÈÛË Ù˘ Û˘Ó‹ıÂÈ·˜ ÙÔ˘ ηӛÛÌ·ÙÔ˜ ÌÂٷ͇ ÙˆÓ ÊÔÈÙËÙÒÓ Î·È ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘˜, Ù· ÔÛÔÛÙ¿ ÙˆÓ Î·ÓÈÛÙÒÓ ÁÔÓ¤ˆÓ ‹Ù·Ó ¯·ÌËÏ¿ ÙfiÛÔ ÁÈ· ÙȘ ÌËÙ¤Ú˜ [120 (37%)] fiÛÔ Î·È ÁÈ· ÙÔ˘˜ ·Ù¤Ú˜ [178 (55%)]. ŸÏÔÈ ÁÓÒÚÈ˙·Ó ÙȘ ‚Ï·‚ÂÚ¤˜ Û˘Ó¤ÂȘ ÙÔ˘ ηӛÛÌ·ÙÔ˜ Î·È ·Ó¤ÊÂÚ·Ó fiÙÈ Â›¯·Ó ·Ú΋ ÂÓË̤ڈÛË [244 (76%)]. ¶·ÚfiÏ· Ù·‡Ù·, 168 (52%) ‰ÂÓ Â›¯·Ó Paediatriki 2009;72:46-50
οÓÂÈ ÚÔÛ¿ıÂȘ Ó· ‰È·Îfi„Ô˘Ó, ÂÓÒ ·fi ·˘ÙÔ‡˜ Ô˘ ›¯·Ó ÂȯÂÈÚ‹ÛÂÈ [142 (44%)] ηӤӷ˜ ‰ÂÓ Â›¯Â ˙ËÙ‹ÛÂÈ ÂÓË̤ڈÛË Î·È ‚Ô‹ıÂÈ· ·fi È·ÙÚÈΤ˜ ‹ ¿ÏϘ ËÁ¤˜. ™¯ÂÙÈο Ì ÙÔ Úfi‚ÏËÌ· Ù˘ ¯Ú‹Û˘ ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ, 50 (5%) ÊÔÈÙËÙ¤˜ ·Ó¤ÊÂÚ·Ó fiÙÈ ¤Î·Ó·Ó ¯Ú‹ÛË Î¿ÔÈ·˜ Ô˘Û›·˜, Û˘ÓËı¤ÛÙÂÚ· ÚÔ˚fiÓÙˆÓ Î¿ÓÓ·‚˘ [32 (64%)], ·ÏÏ¿ Î·È ÎÔη˝Ó˘ [12 (24%)], ¯·ÈÒÓ, LSD, Ecstasy Î.Ù.Ï. [4 (8%)] Î·È ËÚˆ›Ó˘ [2 (4%)]. ø˜ ËÏÈΛ· ÚÒÙ˘ ¯Ú‹Û˘ ·Ó·Ê¤ÚıËΠ·˘Ù‹ ÙˆÓ 15 ÂÙÒÓ [38 (76%)], ÌÂÙ¿ ·fi Û˘Ó·Ó·ÛÙÚÔʤ˜ Ì ¿ÏÏÔ˘˜ ¯Ú‹ÛÙ˜ (Ê›ÏÔ˘˜) [7(14%)], ¯ˆÚ›˜ Ó· ·Ó·ÊÂÚı› οÔÈÔ˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˜ ‹ ȉȷ›ÙÂÚÔ˜ ÏfiÁÔ˜, fiˆ˜ ¿Á¯Ô˜, ηٿıÏÈ„Ë, Û˘Ó‹ıÂÈ· Î.Ï. ø˜ ÚÔ˜ ÙÔ ı¤Ì· Ù˘ Û˘¯ÓfiÙËÙ·˜ ¯Ú‹Û˘, ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ [19 (38%)] ·Ó¤ÊÂÚ·Ó fiÙÈ ‰ÔÎ›Ì·Û·Ó ÌfiÓÔ 1-2 ÊÔÚ¤˜, ÂÓÒ ˘‹Ú¯·Ó Î·È ·˘ÙÔ› Ô˘ ¤Î·Ó·Ó Û˘ÛÙËÌ·ÙÈ΋ ¯Ú‹ÛË 3-4 ÊÔÚ¤˜ ÙË ‚‰ÔÌ¿‰· [17 (34%)]. ªÔÏÔÓfiÙÈ Ë ÌÂÁ¿ÏË ÏÂÈÔ„ËÊ›· [47 (94%)] ÁÓÒÚÈ˙ ÙȘ ÔϤıÚȘ ÂÈÙÒÛÂȘ ÙˆÓ Ô˘ÛÈÒÓ ·˘ÙÒÓ ÛÙËÓ ˘Á›·, ÌfiÓÔ 16 (32%) ‰‹ÏˆÛ·Ó fiÙÈ ÂÈı˘ÌÔ‡Û·Ó Ó· ‰È·Îfi„Ô˘Ó, ÂÓÒ 7 (14%) ›¯·Ó ÙËÓ ¿Ô„Ë fiÙÈ ÔÈ ÂÍ·ÚÙËÛÈÔÁfiÓ˜ Ô˘Û›Â˜ ‰ÂÓ ÌÔÚÔ‡Û·Ó Ó· ‚Ï¿„Ô˘Ó ÙËÓ ˘Á›· ÙÔ˘˜.
™˘˙‹ÙËÛË ∞fi Ù· ·Ú·¿Óˆ Ê·›ÓÂÙ·È fiÙÈ ÂÚÈÛÛfiÙÂÚÔÈ ·fi ÙÔ˘˜ ÌÈÛÔ‡˜ ÊÔÈÙËÙ¤˜ ηٿÁÔÓÙ·Ó ·fi ÙËÓ ∞ı‹Ó·, ÛÙËÓ ÔÔ›· fï˜ ‰È¤ÌÂÓ ÌfiÓÈÌ· Ë ÏÂÈÔ„ËÊ›· (85%), οÙÈ ÙÔ ÔÔ›Ô Û›ÁÔ˘Ú· ·›˙ÂÈ ÙÔ ÚfiÏÔ ÙÔ˘, ÌÈ·˜ Î·È ÛÙȘ ÌÈÎÚfiÙÂÚ˜ ÎÔÈӈӛ˜ Ù· ¿ÓÙ· Á›ÓÔÓÙ·È ÈÔ Â‡ÎÔÏ· ÁÓˆÛÙ¿. ™¯Â‰fiÓ fiÏÔÈ (99%) ›¯·Ó Ê˘ÛÈÎÔ‡˜ ÁÔÓ›˜, ·fiÊÔÈÙÔ˘˜ ‰Â˘ÙÂÚÔ‚¿ıÌÈ·˜ ‹ ÙÚÈÙÔ‚¿ıÌÈ·˜ Âη›‰Â˘Û˘ (81%), ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ÌfiÓÔ 55 (6%) ‹Ù·Ó ‰È·˙¢Á̤ÓÔÈ. ™ÙË Û˘ÓÙÚÈÙÈ΋ ÙÔ˘˜ ÏÂÈÔ„ËÊ›·, ÔÈ ÊÔÈÙËÙ¤˜ ‹Ù·Ó ·fiÊÔÈÙÔÈ ‰ËÌfiÛÈ·˜ ‰Â˘ÙÂÚÔ‚¿ıÌÈ·˜ Âη›‰Â˘Û˘, ÂÓÒ ÙÔ 1/3 ›¯Â Â͈ۯÔÏÈο ÂӉȷʤÚÔÓÙ·, fiˆ˜ Ô ·ıÏËÙÈÛÌfi˜, Ë ÌÔ˘ÛÈ΋, ÔÈ Ù¤¯Ó˜. ∫¿ı ¤Ó·˜ ·fi ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ·˘ÙÔ‡˜ Û›ÁÔ˘Ú· ¤¯ÂÈ ÙË ‰È΋ ÙÔ˘ ÛËÌ·Û›·. ™ÙÔ ı¤Ì· Ù˘ ηٷӿψÛ˘ ÔÈÓÔÓ‡̷ÙÔ˜, ¤Ó·˜ ÛÙÔ˘˜ Ù¤ÛÛÂÚȘ ‰ÂÓ Â›¯Â ÈÂÈ ÔÙ¤, ÂÓÒ, ·fi ·˘ÙÔ‡˜ Ô˘ ¤ÈÓ·Ó, ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ Â›¯·Ó ·Ú¯›ÛÂÈ ÌÂÙ¿ ÙËÓ ËÏÈΛ· ÙˆÓ 15 ¯ÚfiÓˆÓ, ¯ˆÚ›˜ Ó· ¤¯Ô˘Ó ·Ú·Û˘Úı› ·fi Ê›ÏÔ˘˜. ∫·Ù·Ó¿ÏˆÓ·Ó ÂÚÈÛÙ·Ûȷο ÂÏ·ÊÚÈ¿ ÔÙ¿, ΢ڛˆ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ‰È·ÛΤ‰·Û˘ Î·È ‰È·ÎÔÒÓ, ˘‹Ú¯·Ó fï˜ Î·È 17 (2%) Ô˘ ¿ÁÁÈ˙·Ó Ù· fiÚÈ· ÙÔ˘ ·ÏÎÔÔÏÈÛÌÔ‡ (3-6). √È ÌÈÛÔ› ÂÚ›Ô˘ ·Ó¤ÊÂÚ·Ó Ì¤ıË, ¤Ó·˜ ÌÈÎÚfiÙÂÚÔ˜ ·ÚÈıÌfi˜ ·ÓÂÈı‡ÌËÙË ÛÂÍÔ˘·ÏÈ΋ Ú¿ÍË Î·È ¤Ó·˜ ·ÎfiÌ· ÌÈÎÚfiÙÂÚÔ˜ ·ÚÈıÌfi˜ [36 (5%)] ηÎÔÔ›ËÛË ·fi ¿ÏÏÔ ¿ÙÔÌÔ. ¶Ôχ ÛËÌ·ÓÙÈÎfi Â›Ó·È ÙÔ fiÙÈ ‰ÂÓ Ô‰ËÁÔ‡Û·Ó ÌÂÙ¿ ·fi ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜ Î·È ‰ÂÓ Â›¯·Ó ÚÔηϤÛÂÈ
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·49
49
∂Í·ÚÙËÛÈÔÁfiÓ˜ Ô˘Û›Â˜ Û ÊÔÈÙËÙ¤˜ ·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜
ÙÚÔ¯·›· ·Ù˘¯‹Ì·Ù· (7,8). ™Â fiÙÈ ·ÊÔÚ¿ ÙËÓ Î·Ù·Ó¿ÏˆÛË ÔÈÓÔÓ‡̷ÙÔ˜, Ù· ‰Èο Ì·˜ ·ÔÙÂϤÛÌ·Ù· ·ÚÔ˘ÛÈ¿˙Ô˘Ó Â› Ù· ‚ÂÏÙ›ˆ ‰È·ÊÔÚ¤˜, fiˆ˜ 10% ÌÈÎÚfiÙÂÚÔ ÔÛÔÛÙfi ·˘ÙÒÓ Ô˘ ‰ÂÓ Â›¯·Ó ÔÙ¤ ηٷӷÏÒÛÂÈ ÔÈÓfiÓÂ˘Ì· Û ۇÁÎÚÈÛË Ì ÚÔËÁÔ‡ÌÂÓË ·Ó·ÛÎfiËÛË ÙˆÓ ∆ÚÈ·ÓÙ·Ê˘ÏÏ›‰Ô˘-∆ÛÔ˘Ì¿Î·˜ (5) Î·È 20% ÌÈÎÚfiÙÂÚÔ ÔÛÔÛÙfi ·fi ÙË ÛÙ·ÙÈÛÙÈ΋ ÙÔ˘ ∂∫∆∂¶¡ (∂ıÓÈÎfi ∫¤ÓÙÚÔ ∆ÂÎÌËÚ›ˆÛ˘-¶ÏËÚÔÊfiÚËÛ˘ ÁÈ· Ù· ¡·ÚΈÙÈο Î·È ÙËÓ ∆ÔÍÈÎÔÌ·Ó›·), ÂÓÒ 17% ÏÈÁfiÙÂÚÔÈ ‹Ù·Ó ·˘ÙÔ› Ô˘ ›¯·Ó ÌÂı‡ÛÂÈ. ™ËÌ·ÓÙÈÎfiÙÂÚÔ Â›Ó·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÛÙË ‰È΋ Ì·˜ ÌÂϤÙË, fiˆ˜ ·Ó·Ê¤ÚıËÎÂ, ηӤӷ˜ ‰ÂÓ Ô‰ËÁÔ‡Û ÌÂı˘Ṳ̂ÓÔ˜. √È ‰È·ÊÔÚ¤˜ Ì ÙÔ ·Ú·¿Óˆ ¿ÚıÚÔ Èı·Ófiٷٷ ÔÊ›ÏÔÓÙ·È ÛÙÔ fiÙÈ ÂÚÈÏ·Ì‚¿ÓÂÈ ÌÈÎÚfiÙÂÚ˜ ËÏÈ˘. ™Â fiÙÈ ·ÊÔÚ¿ ÙËÓ Â›‰Ú·ÛË ÙˆÓ Û˘ÓËıÂÈÒÓ ÙˆÓ ÁÔÓ¤ˆÓ, ·ÚfiÏÔ Ô˘ ÔÈ Malone Î·È Û˘Ó. (7) ‰›ÓÔ˘Ó ÌÂÁ¿ÏË ÛËÌ·Û›· ÛÙËÓ ÔÈÎÔÁÂÓÂȷ΋ ηٿÛÙ·ÛË, ηıÒ˜ Î·È ÛÙËÓ Î·Ù¿¯ÚËÛË Ô˘ÛÈÒÓ ·fi ÙÔ˘˜ ÁÔÓ›˜, ÛÙȘ ‰ÈΤ˜ Ì·˜ ÂÚÈÙÒÛÂȘ ‰ÂÓ ˘‹Ú¯·Ó ÔÛÔÛÙ¿ Ô˘ ı· ÌÔÚÔ‡Û·Ó Ó· ıˆÚËıÔ‡Ó ÂÈ‚·Ú˘ÓÙÈο. ∆· Â˘Ú‹Ì·Ù¿ Ì·˜, Û ۇÁÎÚÈÛË Ì ·˘Ù¿ Ù˘ ÌÂϤÙ˘ ÙˆÓ Rimza Î·È Û˘Ó. (9), fiÔ˘ ·Ó·Ê¤ÚÂÙ·È fiÙÈ 80% ÙˆÓ ÊÔÈÙËÙÒÓ Ù˘ ÙÚÈÙÔ‚¿ıÌÈ·˜ Âη›‰Â˘Û˘ ÛÙȘ ∏¶∞ ηٷӷÏÒÓÔ˘Ó ÔÈÓfiÓÂ˘Ì·, ηıÒ˜ Î·È fiÙÈ 29% Ô‰ËÁÔ‡Ó ˘fi ÙËÓ Â‹ÚÂÈ· ÔÈÓÔÓ‡̷ÙÔ˜, ·ÔÙÂÏÒÓÙ·˜ ¤ÙÛÈ ÙËÓ ÚÒÙË ·ÈÙ›· ı·Ó¿ÙÔ˘ ÛÙȘ ËÏÈ˘ ÙˆÓ 15-24 ÂÙÒÓ, Ì·˜ οÓÔ˘Ó Ó· ·ÈÛı·ÓfiÌ·ÛÙ οˆ˜ ηχÙÂÚ·. ∆Ô ·›ÛıËÌ· ·˘Ùfi ÂÓÈÛ¯‡ÂÙ·È Î·È ·fi ¿ÏϘ ÂÚÁ·Û›Â˜, fiˆ˜ ·˘Ù‹ ÙˆÓ Noel Î·È Fromme (10) ÔÈ ÔÔ›ÔÈ, Û ÌÈ· ‰ÈÂıÓ‹ ÌÂϤÙË Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÊÔÈÙËÙ¤˜ ·fi ÔÏϤ˜ ¯ÒÚ˜, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÛÔÛÙfi ÚÔ‚ÏËÌ¿ÙˆÓ Û˘ÌÂÚÈÊÔÚ¿˜ Û 8 ÛÙÔ˘˜ 10 ÊÔÈÙËÙ¤˜ Ô˘ ηٷӷÏÒÓÔ˘Ó ÔÈÓfiÓÂ˘Ì·, ηıÒ˜ ›Û˘ Î·È ·fi ÙËÓ ÂÚÁ·Û›· ÙˆÓ Lorente Î·È Û˘Ó. (11) Ô˘ ·Ó·Ê¤ÚÂÈ fiÙÈ 20,4% ÙˆÓ ÊÔÈÙËÙÒÓ Á˘ÌÓ·ÛÙÈ΋˜ ·Î·‰ËÌ›·˜ ÛÙË °·ÏÏ›· ·ÚÔ˘Û›·˙·Ó ÂÚÈÛÛfiÙÂÚ· ·fi 6 ÂÂÈÛfi‰È· ˘ÂÚηٷӿψÛ˘ ÔÈÓÔÓ‡̷ÙÔ˜, ÊÙ¿ÓÔÓÙ·˜ Ù· fiÚÈ· Ù˘ ÙÔÍÈ΋˜ ‰Ú¿Û˘. ™Â fiÙÈ ·ÊÔÚ¿ ÙÔ Î¿ÓÈÛÌ·, Â›Ó·È È‰È·›ÙÂÚ· ·Ú‹ÁÔÚÔ fiÙÈ ÂÚÈÛÛfiÙÂÚÔÈ ·fi ‰‡Ô ÛÙÔ˘˜ ÙÚÂȘ ÊÔÈÙËÙ¤˜ ‰ÂÓ Î¿ÓÈ˙·Ó (12,13). ªÔÏÔÓfiÙÈ ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ‰ÂÓ ·Ô‰¤¯ÔÓÙ·Ó ÙËÓ Â›‰Ú·ÛË ÙˆÓ Û˘Ó·Ó·ÛÙÚÔÊÒÓ, Ë Û˘¯ÓfiÙËÙ· ÙˆÓ Î·ÓÈÛÙÒÓ Û ·˘Ù¤˜ ÍÂÂÚÓÔ‡Û ÙÔ 80% (14,15). ∆· ÔÛÔÛÙ¿ ·˘Ù¿ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÌÈÎÚ‹ ÌfiÓÔ (1,5%) › Ù· ‚ÂÏÙ›ˆ ·fiÎÏÈÛË Û ۇÁÎÚÈÛË Ì ÚÔËÁÔ‡ÌÂÓË ÂÚ¢ÓËÙÈ΋ ÂÚÁ·Û›· Ô˘ ›¯·Ì ·ÚÔ˘ÛÈ¿ÛÂÈ ÚÈÓ ·fi 4 ÂÚ›Ô˘ ¯ÚfiÓÈ· (16). ŸÌˆ˜, Â¿Ó Û˘ÁÎÚ›ÓÔ˘Ì ÙÔ ‰ÈÎfi Ì·˜ 34% Ì ÙÔ 28,5% ÙˆÓ ∏¶∞ (9) ‹ ÙÔ 15,3-27,6% Ù˘ ∫ÔÚ¤·˜, Ô˘ ·Ó·Ê¤ÚÔ˘Ó ÔÈ Ham Î·È Û˘Ó. (17), ηıÒ˜ Î·È Ì ÙȘ ÚÔÛ¿ıÂȘ Ô˘ Á›ÓÔÓÙ·È ÛÙÔÓ ∫·Ó·‰¿ [Kischuk Î·È Û˘Ó. (18)] ‹ ÛÙȘ ∏¶∞ [Staten Î·È Û˘Ó.
(19]), Ê·›ÓÂÙ·È fiÙÈ Ë ÌÈÎÚ‹ ‚ÂÏÙ›ˆÛË Ô˘ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔ˘˜ ‰ÈÎÔ‡˜ Ì·˜ ÊÔÈÙËÙ¤˜ ‰ÂÓ Ú¤ÂÈ Ó· Ì·˜ ÈηÓÔÔÈ›, ·ÏÏ¿ ÙÔ˘Ó·ÓÙ›ÔÓ Ó· Ì·˜ οÓÂÈ Ó· ·˘Í‹ÛÔ˘Ì ÙȘ ÚÔÛ¿ıÂȤ˜ Ì·˜ ÁÈ· ÙËÓ Î·Ï‡ÙÂÚË ÂÓË̤ڈۋ ÙÔ˘˜. ø˜ ÚÔ˜ ÙÔ Úfi‚ÏËÌ· Ù˘ ¯Ú‹Û˘ ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ, ÌÔÏÔÓfiÙÈ ÙÔ ÔÛÔÛÙfi 5% Â›Ó·È Û¯ÂÙÈο ÌÈÎÚfi, ‰ÂÓ Â›Ó·È Â˘Î·Ù·ÊÚfiÓËÙÔ, ÂÓÒ ÂÓÙ‡ˆÛË ÚÔηÏ› Î·È Ë ÌÈÎÚ‹ ËÏÈΛ· ¤Ó·Ú͢, Ô˘ ‰Â›¯ÓÂÈ ÙË ÛËÌ·Û›· ·˘ÙÔ‡ Ô˘ ·Ó·Ê¤ÚÂÈ Ô Patton (20), fiÙÈ Ë Î·Ù¿¯ÚËÛË ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ ·fi ÂÊ‹‚Ô˘˜ Â›Ó·È Ë ·È‰È·ÙÚÈ΋ ‰È¿ÁÓˆÛË Ô˘ Û˘¯ÓfiÙÂÚ· ‰È·Ê‡ÁÂÈ. √È ÂÚÈÛÛfiÙÂÚÔÈ ¯ÚËÛÈÌÔÔÈÔ‡Û·Ó ÚÔ˚fiÓÙ· οÓÓ·‚˘ ‹ ÎÔη˝ÓË (21-23), ÂÈÏÔÁ¤˜ Ô˘ Û˘ÌʈÓÔ‡Ó Ì ·˘Ù¤˜ Ô˘ ·Ó·Ê¤ÚÂÈ Ô ª·ÚÛ¤ÏÔ˜ (24) ÛÙÔ ‚È‚Ï›Ô ÙÔ˘. ∂›Û˘, ¤¯ÂÈ ÛËÌ·Û›· ˆ˜ Ë ¯Ú‹ÛË ÁÈÓfiÙ·Ó ÌÂÙ¿ ·fi Û˘Ó·Ó·ÛÙÚÔÊ‹ Ì ¯Ú‹ÛÙ˜, ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ¯ˆÚ›˜ οÔÈÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ÏfiÁÔ, fiˆ˜ Î·È fiÙÈ ·Ó Î·È Û¯Â‰fiÓ fiÏÔÈ ÁÓÒÚÈ˙·Ó ÙȘ ÔϤıÚȘ ÂÈÙÒÛÂȘ ÛÙËÓ ˘Á›·, ÌfiÓÔ ¤Ó·˜ ÛÙÔ˘˜ ÙÚÂȘ ‰‹ÏˆÓ fiÙÈ ÂÈı˘ÌÔ‡Û ӷ ‰È·Îfi„ÂÈ, ‰›¯ˆ˜ Ó· ¤¯ÂÈ ˙ËÙ‹ÛÂÈ È·ÙÚÈ΋ ‹ ¿ÏÏË ‚Ô‹ıÂÈ·, οÙÈ Ô˘ ›Û¯˘Â Î·È ÁÈ’ ·˘ÙÔ‡˜ Ô˘ οÓÈ˙·Ó (25-26). ∆· ·Ú·¿Óˆ ÔÛÔÛÙ¿ Â›Ó·È ÂÓı·ÚÚ˘ÓÙÈο (fi¯È ÂÊËÛ˘¯·ÛÙÈο), Û ۇÁÎÚÈÛË Ì ·˘Ù¿ Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÈ Gledhill-Hoyt Î·È Û˘Ó. (27) ÁÈ· ÙȘ ∏¶∞, fiÔ˘ ÛÙË ÌÂϤÙË Ô˘ ÂÚÈÏ¿Ì‚·Ó 119 Û¯ÔϤ˜ ÙÚÈÙÔ‚¿ıÌÈ·˜ Âη›‰Â˘Û˘, ÙÔ ÔÛÔÛÙfi ¯ÚËÛÙÒÓ Ì·ÚÈ¯Ô˘¿Ó·˜ ¤ÊÙ·Ó ÙÔ 15,7%, οÙÈ Ô˘ ÂȂ‚·ÈÒÓÔ˘Ó Î·È ÔÈ Johnston Î·È Û˘Ó. (28), ·Ó·Ê¤ÚÔÓÙ·˜ fiÙÈ Ë Ì·ÚÈ¯Ô˘¿Ó· ·ÔÙÂÏ› ÙËÓ ÚÒÙË Û ÚÔÙ›ÌËÛË ÂÍ·ÚÙËÛÈÔÁfiÓÔ Ô˘Û›·, fiˆ˜ ·Ú·ÙËÚ‹ıËÎÂ Î·È ÛÙÔ˘˜ ÊÔÈÙËÙ¤˜ Ê·Ú̷΢ÙÈ΋˜ Ù˘ ∆Û¯›·˜, ÛÙËÓ ÂÚÁ·Û›· ÙˆÓ Kavalirova Î·È Visnovsky (29). ∆¤ÏÔ˜, ·ÚfiÏÔ Ô˘ ÁÈ· ÙÔ fiÛÔ Â›Î·ÈÚÔ Â›Ó·È ÙÔ ı¤Ì· Ù˘ ÂÚÁ·Û›·˜ ·˘Ù‹˜ ‰ÂÓ ÓÔÌ›˙Ô˘Ì ˆ˜ ˘¿Ú¯Ô˘Ó ·ÌÊÈ‚Ôϛ˜, ÈÛÙ‡ԢÌ fiÙÈ ·Í›˙ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ ÙËÓ Ë̤ڷ Ô˘ ¤ÁÈÓ·Ó ÔÈ ÙÂÏÂ˘Ù·›Â˜ ‰ÈÔÚıÒÛÂȘ, ‰ËÌÔÛȇÙËÎ·Ó ÙÚ›· ÔÏÔÛ¤Ïȉ· ¿ÚıÚ· Ì ·ÚfiÌÔÈÔ ı¤Ì· Û ‰‡Ô ʇÏÏ· ÙÔ˘ ϤÔÓ ¤ÁÎÚÈÙÔ˘ ΢ÚȷοÙÈÎÔ˘ Ù‡Ô˘ (30-32).
™˘ÌÂÚ¿ÛÌ·Ù· ∆Ô Û¯ÂÙÈο ÌÈÎÚfiÙÂÚÔ ÔÛÔÛÙfi ÙˆÓ Î·ÓÈÛÙÒÓ Û ۯ¤ÛË Ì ÚÔËÁÔ‡ÌÂÓ˜ ÌÂϤÙ˜ ηٿ ¿Û· Èı·ÓfiÙËÙ· ÔÊ›ÏÂÙ·È ÛÙËÓ ÂÈÙ˘¯›· Ù˘ ·ÓÙÈηÓÈÛÙÈ΋˜ ÂÎÛÙÚ·Ù›·˜ Ô˘ ÂÊ·ÚÌfiÛıËΠ·fi ÎÚ·ÙÈÎÔ‡˜ Î·È ¿ÏÏÔ˘˜ ÊÔÚ›˜, ÛÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ ÂÈÎÔÛȤÓÙ ¯ÚfiÓˆÓ. ŸÌˆ˜, fiˆ˜ Ê·›ÓÂÙ·È ÛÙË Û‡ÁÎÚÈÛË Ì ٷ ÔÛÔÛÙ¿ ¿ÏÏˆÓ ¯ˆÚÒÓ, ÔÈ ÚÔÛ¿ıÂȤ˜ Ì·˜ Ú¤ÂÈ Ó· Û˘Ó¯ÈÛÙÔ‡Ó Î·È Ó· ÂÈÙ·ıÔ‡Ó. ™Â fiÙÈ ·ÊÔÚ¿ ÛÙËÓ Ô‰‹ÁËÛË ÌÂÙ¿ ·fi ηٷӿψÛË ÔÈÓÔÓ‡̷ÙÔ˜, Ê·›ÓÂÙ·È fiÙÈ Ë Û˘ÛÙËÌ·ÙÈ΋ ¶·È‰È·ÙÚÈ΋ 2009;72:46-50
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ÂÓË̤ڈÛË ÁÈ· ÙÔ˘˜ Ôχ ÛÔ‚·ÚÔ‡˜ ÎÈÓ‰‡ÓÔ˘˜, Ù· Û˘¯Ó¿ ·ÏÎÔÙ¤ÛÙ, ηıÒ˜ Î·È Ë ·˘ÛÙËÚ‹ ÓÔÌÔıÂÛ›·, ›¯·Ó ηϿ ·ÔÙÂϤÛÌ·Ù·. ¶ÈÛÙ‡ԢÌ fiÙÈ ı· Ú¤ÂÈ Ó· ÂÓÙ·ıÔ‡Ó ÔÈ ÚÔÛ¿ıÂȘ ÙfiÛÔ ·fi ÙËÓ ÔÈÎÔÁ¤ÓÂÈ· fiÛÔ Î·È ·fi ÙÔ Û¯ÔÏ›Ô, fiˆ˜ Î·È ·fi fiÏÔ˘˜ ÙÔ˘˜ ÎÚ·ÙÈÎÔ‡˜ Î·È ÌË ÎÚ·ÙÈÎÔ‡˜ ÊÔÚ›˜ ˘Á›·˜, Ô‡Ùˆ˜ ÒÛÙ ӷ ÂÈÙ¢¯ı› Ô ÛÙfi¯Ô˜ Û fiÙÈ ·ÊÔÚ¿ ÙÔ ·ÏÎÔfiÏ Î·È ÙÔ Î¿ÓÈÛÌ·, ·ÏÏ¿ Î·È ÙË ¯Ú‹ÛË ¿ÏÏˆÓ ÂÍ·ÚÙËÛÈÔÁfiÓˆÓ Ô˘ÛÈÒÓ. ¢ÂÓ Ú¤ÂÈ ‰Â Ó· ‰È·Ê‡ÁÂÈ Ë ÛËÌ·Û›· ÙÔ˘ fiÙÈ ÙÔ ˘ÏÈÎfi Ù˘ ÂÚÁ·Û›·˜ Ì·˜ ·ÊÔÚ¿ ÊÔÈÙËÙ¤˜ ÙÚÈÙÔ‚¿ıÌÈ·˜ Âη›‰Â˘Û˘ Î·È Ì¿ÏÈÛÙ· Û¯ÔÏÒÓ Â·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜.
µÈ‚ÏÈÔÁÚ·Ê›· 1. O’Malley PM, Johnston LD. Epidemiology of alcohol and other drug use among American college students. J Stud Alcohol Suppl 2002;14:23-39. 2. Bower AM. Are college students alcoholics? J Am Coll Health 2002;50:253-255. 3. Ziemelia A, Bucknam RB, Elfessi AM. Prevention efforts underlying decreases in binge drinking at institutions of higher education. J Am Coll Health 2002;50:238-249. 4. Toomey TL, Wagenaar LC. Environmental policies to reduce college drinking: options and research findings. J Stud Alcohol Suppl 2002;14:193-205. 5. ∆ÚÈ·ÓÙ·Ê˘ÏÏ›‰Ô˘ ∞, ∆ÛÔ˘Ì¿Î·˜ ∫. ∞ÏÎÔfiÏ Î·È ÂÊ˂›·. ¢ÂÏÙ. ∞ã ¶·È‰È·ÙÚ. ∫ÏÈÓ. ¶·ÓÂ. ∞ıËÓÒÓ 2006;53:33-40. 6. World Health Organisation: Global Status Report on alcohol (Country profiles) 2004; 1-5. 7. Malone SM, Iacono WG, McGue M. Drinks of the father’s maximum number of drinks consumed predicts externalizing disorders, substance use, and substance use disorders in preadolescent and adolescent offspring. Alcohol Clin Exp Res 2002;26:1823-1832. 8. Chassin L, For DB, King KM. Trajectories of alcohol and drug use and dependence from adolescence to adulthood: the effects of familial alcoholism and personality. J Abnorm Psychol 2004;113:483. 9. Rimza ME, Moses KS, Ches RD. Substance abuse on the college campus. Pediatr Clin North AM. 2005;52:307-319. 10. Noel DJ, Fromme K. Event level covariation of alcohol intoxication and behavioral risks during the first year of college. J Consult Clin Psychol 2007;75:294-301. 11. Lorente FO, Peretti-Watel P, Griffek J, Grelet L. Alcohol use and intoxication in sport university students. Alcohol Alcohol 2003;38:427-430. 12. Ennet ST. Mediation in a family-directed program for prevention of adolescent tobacco and alcohol use. Prev Med 2001;33:333-346. 13. Centers for Disease Control and Prevention. Tobacco use United States, 1900-1999. MMWR Morb Mortal Wkly Rep 1999;48:986-993.
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14. Klein JD, Camenga DR. Tobacco prevention and cessation in pediatric patients. Pediatr Rev 2004;25:16-24. 15. Rigoti N, Lee JE, Wwchsler H. US college students’ use of tobacco products: results of a national survey. JAMA 2000;284:699-705. 16. ∞ÓÙˆÓÈ¿‰Ë˜ ™, ∫˘ÚÈ·ÎÔÔ‡ÏÔ˘ ™, ∞ÚÁ˘ÚÔÔ‡ÏÔ˘ µ, ∫Ú›ÎÔ˜ •. µ·ıÌfi˜ ÁÓÒÛ˘ ÙˆÓ ÂȤ‰ˆÓ ÏÈȉ›ˆÓ ÙÔ˘ ·›Ì·ÙÔ˜ Û ÊÔÈÙËÙ¤˜ ·ÁÁÂÏÌ¿ÙˆÓ ˘Á›·˜- ÚfiÓÔÈ·˜. ¶·È‰È·ÙÚÈ΋ 2004;67:195-199. 17. Ham OK, Lee YS. Use of the transtheoretical model to predict stages of smoking sesation in Korean adolescents. J Sch Health 2007;77:319-326. 18. Kischuk N, Trembley K, Lapierre J, Heneman B, O’Loughlin J. Qualitative investigation of young smokers and ex-smokers views on smoking cessation methods. Nicotine Tob Res 2004;6:491-500. 19. Staten RR, Ridner SL. College students perspective on smoking cessation: "If the message doesn’t speak to me, I don’t hear it". Issues Ment Health Nurs 2007;28:101-115. 20. Patton GC. Puberty and the onset of substance use and abuse. Pediatrics 2004;114:300-306. 21. Greydanus DE, Patel DR. Substance abuse in adolescence: a complex conundrum for the clinician. Pediatr Clin North Am 2003;50:1179-1223. 22. Schwartz RH, Miller NS. MDMA (ecstasy) and the rave: a review. Pediatrics 1997;100:705-708. 23. American Academy of Pediatrics Committee on substance abuse. A guide for health professionals. 2nd ed. Elk Grove Village (IL): American Academy of Pediatrics; 2002. 24. ª·ÚÛ¤ÏÔ˜ ª. ∂Í·ÚÙËÛÈÔÁfiÓ˜ Ô˘Û›Â˜. ∞ı‹Ó·: ∂ΉfiÛÂȘ ∆˘ˆı‹Ùˆ; 2005. 25. ∞ÓÙˆÓÈ¿‰Ë˜ ™. ¡ÙfiÈÓÁÎ Û ·È‰È¿, ÂÊ‹‚Ô˘˜ Î·È Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ. ¶·È‰È·ÙÚÈ΋ 2006;69:351-356. 26. Baltimore American College Health Associasion Survey. National College Health Assesment: reference group executive summary. Baltimore (MD): American College Health Association; 2004. 27. Gledhill-Hoyt J, Lee H, Strote S, Wechsler H. Increased use of marijuana and other illicid drugs at US colleges in the 1990s: results in three national surveys. Addiction 2000;95:1655-1657. 28. Johnston LD, O’Malley PM, Bachman JG, editors. Monitoring the future. In: National results on adolescent drug use: overview of key findings, 2001. Bethesda (MD): National Institute on Drug Abuse; 2002. p. 1-61. 29. Kavalirova A, Visnovsky P. Use of marijuana in pharmacy students (2000-2005). Biomed Pop Med Fac Univ Palackej Olomouc Chech Repub 2005;149:477-480. 30. ∫·Ú¿Ï˘ ™. ∞Ó‹ÏÈÎÔÈ ÛÙ· ‰›¯Ù˘· ÙÔ˘ ÛÎÏËÚÔ‡ ·ÏÎÔfiÏ. ∫·ıËÌÂÚÈÓ‹ Ù˘ ∫˘Úȷ΋˜, 18/5/2008, ÛÂÏ›‰· 39. 31. º˘ÓÙ·Ó›‰Ô˘ ∂. ∂ÎÙfi˜ ÓfiÌÔ˘ ÙÔ ÙÛÈÁ¿ÚÔ. ∆Ô µ‹Ì·, ∫˘Úȷ΋ 18/5/2008, ÛÂÏ›‰· 10 32. ¡ÈÎÔÏfiÔ˘ÏÔ˜ π, ª›ÙÛÈη ¶. √È ÁÂÈÙÔÓȤ˜ Ù˘ ËÚˆ›Ó˘. ∆Ô µ‹Ì·, ∫˘Úȷ΋ 18/5/2008, ÛÂÏ›‰· 44.
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∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏
CASE REPORT
51
梉ԸԷωÔÛÙÂÚÔÓÈÛÌfi˜ Ù‡Ô˘ 1 Û ‚Ú¤ÊÔ˜ Ã. ¢·ÛηÏÔÔ‡ÏÔ˘, £. ∆ÛÂÎÔ˘Ú¿, ∞. ∆ÛÈÏÈÌÈÁοÎË ¶ÂÚ›ÏË„Ë: √ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜ Ù‡Ô˘ 1 Â›Ó·È ÌÈ· Û¿ÓÈ· ÎÏËÚÔÓÔÌÈ΋ ÓfiÛÔ˜ Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·ÓÙ›ÛÙ·ÛË ÛÙË ‰Ú¿ÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÂÚ›ÙˆÛË ·ÁÔÚÈÔ‡ 37 ËÌÂÚÒÓ Ì „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi Ù‡Ô˘ 1, Ô˘ ÚÔÛ‹Ïı ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÏfiÁˆ ÌÂȈ̤Ó˘ Û›ÙÈÛ˘, ·Ó·ÚÎÔ‡˜ ÚfiÛÏ˄˘ ‚¿ÚÔ˘˜, ‰˘ÛÙÚÔÊ›·˜ Î·È ·Ê˘‰¿ÙˆÛ˘. √ ‚ÈÔ¯ËÌÈÎfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍ ˘ÔÓ·ÙÚÈ·ÈÌ›· ˘ÂÚηÏÈ·ÈÌ›·, ·˘ÍË̤ÓÔ Ó¿ÙÚÈÔ Ô‡ÚˆÓ Î·È ˘„ËϤ˜ ÙÈ̤˜ ÚÂÓ›Ó˘ Î·È ·Ï‰ÔÛÙÂÚfiÓ˘. √ ÏÔÈfi˜ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜, Ë ÎÚ·ÙÈÓ›ÓË, ÔÈ Î·ÏÏȤÚÁÂȘ ·›Ì·ÙÔ˜ Î·È Ô‡ÚˆÓ, ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÓÂÊÚÒÓ, Ë ACTH, Ë ÎÔÚÙÈ˙fiÏË Î·È Ë 17-√∏ ÚÔÁÂÛÙÂÚfiÓË ‹Ù·Ó ÂÓÙfi˜ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÔÚ›ˆÓ. √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÙˆÓ ÁÔÓÈÒÓ ¤‰ÂÈÍ ·˘ÍË̤ÓË ÙÈÌ‹ ·Ï‰ÔÛÙÂÚfiÓ˘ ÛÙË ÌËÙ¤Ú·. ∏ ÌÔÚȷ΋ ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ ¤‰ÂÈÍ ÙÚÂȘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡˜ ÛÙÔ ÂÍfiÓÈÔ 2 ÛÙÔ ÁÔÓ›‰ÈÔ Ô˘ Έ‰ÈÎÔÔÈ› ÙÔÓ ˘Ô‰Ô¯¤· ÙˆÓ ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ, Ô Û˘Ó‰˘·ÛÌfi˜ ÙˆÓ ÔÔ›ˆÓ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÎÏÈÓÈ΋ ¤ÎÊÚ·ÛË ÙÔ˘ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Ù‡Ô˘ 1.
B’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, µÂÓÈ˙¤ÏÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ AÏÏËÏÔÁÚ·Ê›·: ∞Ì·Ï›· ∆ÛÈÏÈÌÈÁοÎË tsiliman@yahoo.gr ∏ÚÔ‰fiÙÔ˘ 214 ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ 71601
§¤ÍÂȘ ÎÏÂȉȿ: 梉ԸԷωÔÛÙÂÚÔÓÈÛÌfi˜, ·ÒÏÂÈ· ¿Ï·ÙÔ˜, ·Ï‰ÔÛÙÂÚfiÓË, ˘ÔÓ·ÙÚÈ·ÈÌ›·, ˘ÂÚηÏÈ·ÈÌ›·, ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË, ·Ó·Ú΋˜ ÚfiÛÏË„Ë ‚¿ÚÔ˘˜.
Type 1 pseudohypoaldosteronism in an infant C. Daskalopoulou, T. Tsekoura, A. Tsilimigaki Abstract: Type 1 pseudohypoaldosteronism is a rare inherited disorder characterized by insensitivity to the action of aldosterone. The case is reported of a 37 day-old boy with type 1 pseudohypoaldosteronism, admitted because of poor feeding, failure to thrive, dystrophy and dehydration. Biochemical studies revealed hyponatraemia, hyperkalaemia, increased urinary sodium concentration and increased plasma concentrations of aldosterone and renin. Serum levels of creatinine, cortisol, ACTH and 17OH progesterone, blood and urine cultures and ultrasound of the kidneys were normal. Molecular genetic studies showed three polymorphisms within the exon 2 of the mineralocorticoid receptor gene. The combination of these polymorphisms can induce the clinical expression of type 1 pseudohypoaldosterinism.
2nd Department of Paediatrics, “Venizelio” General Hospital, Heraklion, Crete Correspondence: Amalia Tsilimigaki tsiliman@yahoo.gr 214, Irodotou St. Heraklion, Crete, 71601, Greece
Key words: type 1 pseudohypoaldosteronism, salt wasting, plasma aldosterone, hyponatraemia, hyperkalaemia, metabolic acidosis, failure to thrive.
∂ÈÛ·ÁˆÁ‹ √ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜ Â›Ó·È ¤Ó· ÎÏÈÓÈÎfi Û‡Ó‰ÚÔÌÔ Ì ÂÙÂÚoÁ¤ÓÂÈ· Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙË ÓÂÊÚÈ΋ ‹ Î·È Û˘ÛÙËÌ·ÙÈ΋ ·ÓÙ›ÛÙ·ÛË ÛÙË ‰Ú¿ÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘. √È ·Èٛ˜ ·ÓÙ›ÛÙ·Û˘ ÛÙËÓ ·Ï‰ÔÛÙÂÚfiÓË ÌÔÚ› Ó· Â›Ó·È ÚˆÙÔ·ı›˜ (ÎÏËÚÔÓÔÌÈΤ˜) ‹ ‰Â˘ÙÂÚÔ·ı›˜ (›ÎÙËÙ˜). √È ÚˆÙÔ·ı›˜ ÌÔÚʤ˜ ·ÔÙÂÏÔ‡ÓÙ·È ·fi ‰‡Ô ‰È·ÎÚÈÙ¿ ÎÏËÚÔÓÔÌÈο Û‡Ó‰ÚÔÌ·, ÙÔÓ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi Ù‡Ô˘ 1 (PHA 1) Î·È ÙÔÓ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi Ù‡Ô˘ 2 (PHA 2 ‹ Û‡Ó‰ÚÔÌÔ GÔrdon) (1). ∆· Û˘¯ÓfiÙÂÚ· ·›ÙÈ· ÙÔ˘ ‰Â˘ÙÂÚÔ·ıÔ‡˜ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Â›Ó·È ÏÔÈÌÒÍÂȘ ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, Ì ‹ ¯ˆÚ›˜ ·ÔÊÚ·ÎÙÈΤ˜ ÓÂÊÚÈΤ˜ ‚Ï¿‚˜, Ô˘ ‰È·ÈÛÙÒÓÂÙ·È Û¿ÓÈ· Û ‚Ú¤ÊË (2).
¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÂÚ›ÙˆÛË ‚Ú¤ÊÔ˘˜ Ì „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi Ù‡Ô˘ 1 ÁÈ· Ó· ÙÔÓÈÛı› Ë Û·ÓÈfiÙËÙ· Î·È Ë ÛËÌ·Û›· Ù˘ ¤ÁηÈÚ˘ ‰È¿ÁÓˆÛ˘ ÛÙËÓ ÚÒÙË ‚ÚÂÊÈ΋ ËÏÈΛ·.
¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ AÁfiÚÈ ËÏÈΛ·˜ 37 ËÌÂÚÒÓ ÚÔÛ‹Ïı ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÏfiÁˆ ÌÂȈ̤Ó˘ Û›ÙÈÛ˘ Î·È ÛÙ·ÛÈÌfiÙËÙ·˜ ‚¿ÚÔ˘˜. ¶ÚfiÎÂÈÙ·È ÁÈ· ÙÔ ÚÒÙÔ ·È‰› Ê·ÈÓÔÙ˘Èο ˘ÁÈÒÓ ÁÔÓ¤ˆÓ, Ô˘ ÁÂÓÓ‹ıËΠ̠ηÈÛ·ÚÈ΋ ÙÔÌ‹ ÌÂÙ¿ ·fi ·ËÛË 36 ‚‰ÔÌ¿‰ˆÓ, Ì ‚¿ÚÔ˜ Á¤ÓÓËÛ˘ 2880 g. TË 14Ë Ë̤ڷ ˙ˆ‹˜ ÓÔÛËχÙËΠ۠ªÔÓ¿‰· ¡ÂÔÁÓÒÓ ÁÈ· ›ÎÙÂÚÔ. £‹Ï·Û ÁÈ· 14 Ë̤Ú˜ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ¤Ï·‚ ÙÚÔÔÔÈË̤ÓÔ Á¿Ï·. ∆Ô ÔÈÎÔÁÂÓÂÈ·Îfi ·Ó·ÌÓËÛÙÈÎfi ·Ó·Ê¤ÚÂÙ·È ÂχıÂÚÔ. ¶·È‰È·ÙÚÈ΋ 2009;72:51-54
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·52
52
Ã. ¢·ÛηÏÔÔ‡ÏÔ˘ Î·È Û˘Ó.
∆Ô ‚Ú¤ÊÔ˜ ÛÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ˘ ‹Ù·Ó ‰˘ÛÙÚÔÊÈÎfi, Ì ÎÏÈÓÈο Â˘Ú‹Ì·Ù· ·Ê˘‰¿ÙˆÛ˘, ı: 37ÔC, ÛʇÍÂȘ 144/min Î·È ∞¶: 85/45 mmHg. µ¿ÚÔ˜ ÂÈÛfi‰Ô˘ 2810 g (<3Ë ∂£), Ì‹ÎÔ˜ ÛÒÌ·ÙÔ˜ 53 cm (50‹ ∂£) Î·È ÂÚ›ÌÂÙÚÔ˜ ÎÂÊ·Ï‹˜ 35 cm (10Ë-25Ë ∂£). ∞fi ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË ÙˆÓ Û˘ÛÙËÌ¿ÙˆÓ ‰ÂÓ ÚԤ΢„·Ó ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍÂ: ÁÂÓÈ΋ ·›Ì·ÙÔ˜ Î·È TKE ÌÂ Ê˘ÛÈÔÏÔÁÈΤ˜ ÙÈ̤˜, CRP 0,01 mg/dl, ÁÏ˘Îfi˙Ë 77 mg/dl, ÎÚ·ÙÈÓ›ÓË 0,5 mg/dl, Ô˘Ú›· 59 mg, Ê˘ÛÈÔÏÔÁÈ΋ Ë·ÙÈ΋ ÏÂÈÙÔ˘ÚÁ›·, Ca 10,7 mg/dl, Na 129 mmol/l Î·È K 6,6 mmol/l/dl, Cl 97 mmol/l, ‰ÈÙÙ·ÓıÚ·ÎÈο HCO3: 18 mmol/l Î·È ¡a Ô‡ÚˆÓ: 56 mmol/l (·˘ÍË̤ÓÔ). √È Î·ÏÏȤÚÁÂȘ ·›Ì·ÙÔ˜ Î·È Ô‡ÚˆÓ ‹Ù·Ó ÛÙ›Ú˜ Î·È ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÙˆÓ ÓÂÊÚÒÓ Ê˘ÛÈÔÏÔÁÈÎfi. ∆Ô ‚Ú¤ÊÔ˜ Ù¤ıËΠ۠ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ Î·È ¯ÏˆÚÈÔ‡¯Ô˘ Ó·ÙÚ›Ô˘. ∆Ș ÂfiÌÂÓ˜ Ë̤Ú˜, Ë Û›ÙÈÛ‹ ÙÔ˘ ‚ÂÏÙÈÒıËÎÂ Î·È ‰ÈÂÎfiË Ë ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ. ∆Ô 6Ô ÂÈÎÔÛÈÙÂÙÚ¿ˆÚÔ Ù˘ ÓÔÛËÏ›·˜, ÙÔ ‚Ú¤ÊÔ˜ ·ÚÔ˘Û›·Û ÂÎ Ó¤Ô˘ ÌÂȈ̤ÓË Û›ÙÈÛË, ÂÓÒ Ô ‚ÈÔ¯ËÌÈÎfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍ ˘ÔÓ·ÙÚÈ·ÈÌ›· Î·È ˘ÂÚηÏÈ·ÈÌ›·, ÌÂ Ê˘ÛÈÔÏÔÁÈΤ˜ ÙÈ̤˜ ÎÔÚÙÈ˙fiÏ˘, 17-√∏ ÚÔÁÂÛÙÂÚfiÓ˘ Î·È ACTH Ì ˘„ËϤ˜ ÙÈ̤˜ ÚÂÓ›Ó˘ >310 pg/ml (º∆ <130 pg/ml ÁÈ· ‚Ú¤ÊË) Î·È ·Ï‰ÔÛÙÂÚfiÓ˘ 16000 pg/ml (º∆ <50-900 pg/ml ÁÈ· ‚Ú¤ÊË). √ ·ÛıÂÓ‹˜ ·ÓÙÈÌÂÙˆ›ÛÙËΠ̠¯ÏˆÚÈÔ‡¯Ô Ó¿ÙÚÈÔ ·fi ÙÔ ÛÙfiÌ·, Ì ı·̷ÙÈ΋ ‚ÂÏÙ›ˆÛË ÛÙË Û›ÙÈÛË Î·È ÛÙËÓ ÚfiÛÏË„Ë ‚¿ÚÔ˘˜. √ ¤ÏÂÁ¯Ô˜ ÙˆÓ ÁÔÓ¤ˆÓ ¤‰ÂÈÍ ·˘ÍË̤ÓË ÙÈÌ‹ ·Ï‰ÔÛÙÂÚfiÓ˘ ÛÙË ÌËÙ¤Ú· (1909 pg/ml, Ì º∆ 35-310 pg/ml ÁÈ· ÂÓ‹ÏÈΘ), ÌÂ Ê˘ÛÈÔÏÔÁÈΤ˜ ÙÈ̤˜ ËÏÂÎÙÚÔÏ˘ÙÒÓ Î·È ÚÂÓ›Ó˘. ∞fi ÙË Ï‹„Ë ·Ó·Ï˘ÙÈÎfiÙÂÚÔ˘ ÈÛÙÔÚÈÎÔ‡ ÚԤ΢„ fiÙÈ Ë ÌËÙ¤Ú· ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ· ›¯Â ÚÔ‚Ï‹Ì·Ù· Û›ÙÈÛ˘ Î·È ·Ó·Ú΋ ÚfiÛÏË„Ë ‚¿ÚÔ˘˜, ÂÓÒ ÛÙËÓ Î·ıËÌÂÚÈÓ‹ Ù˘ ‰È·ÙÚÔÊ‹ ÚÔÛı¤ÙÂÈ ÌÂÁ¿Ï˜ ÔÛfiÙËÙ˜ ·Ï·ÙÈÔ‡. ∏ ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÙÔ˘ DNA ÙÔ˘ ‚Ú¤ÊÔ˘˜ Û ΤÓÙÚÔ ÙÔ˘ Â͈ÙÂÚÈÎÔ‡ ¤‰ÂÈÍ ÙËÓ ·ÚÔ˘Û›· ÔÏ˘ÌÔÚÊÈÛÌÒÓ Û ÙÚÂȘ ÁÂÓÂÙÈÎÔ‡˜ ÙfiÔ˘˜ ÛÙÔ ÂÍfiÓÈÔ 2 ÙÔ˘ ÁÔÓȉ›Ô˘ ÙÔ˘ ˘Ô‰Ô¯¤· ÙˆÓ ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ (MR). ™˘ÓÂÛÙ‹ıË ¤ÏÂÁ¯Ô˜ Î·È ÙˆÓ ÁÔÓ¤ˆÓ ÁÈ· Ó· ‰È·ÈÛÙˆı› ·Ó ÚfiÎÂÈÙ·È ÁÈ· ÛÔÚ·‰È΋ ÌÔÚÊ‹ ‹ ÁÈ· ·˘ÙÔۈ̷ÙÈ΋ ÂÈÎÚ·ÙËÙÈ΋ ÎÏËÚÔÓÔÌÈÎfiÙËÙ·. ∆Ô ‚Ú¤ÊÔ˜ ÂÍ‹ÏıÂ, Ì ԉËÁ›Â˜ ÁÈ· Ï‹„Ë ¯ÏˆÚÈÔ‡¯Ô˘ Ó·ÙÚ›Ô˘ ·fi ÙÔ ÛÙfiÌ· Î·È ÁÈ· Ù·ÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË. ∂·ÓÂÎÙÈÌ‹Û·Ì ÙÔ ·È‰› Û ËÏÈΛ· 20 ÌËÓÒÓ Î·È Ù· ۈ̷ÙÔÌÂÙÚÈο ÙÔ˘ ÛÙÔȯ›· ‹Ù·Ó ‚¿ÚÔ˜ ÛÒÌ·ÙÔ˜ 11.600 g (25Ë ∂£), ‡„Ô˜ ÛÒÌ·ÙÔ˜ 85 cm (50‹ ∂£) Î·È ÂÚ›ÌÂÙÚÔ˜ ÎÂÊ·Ï‹˜ 48 cm (25Ë ∂£), ÌÂ Ê˘ÛÈÔÏÔÁÈ΋ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍË. √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍÂ Ê˘ÛÈÔÏÔÁÈΤ˜ ÙÈ̤˜ ËÏÂÎÙÚÔÏ˘ÙÒÓ Î·È ÚÂÓ›Ó˘, ÂÓÒ Ù· ›‰· Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ ·Ú¤ÌÂÈÓ·Ó ˘„ËÏ¿ (4937 pg/ml, º∆ <50900 pg/ml ÁÈ· ‚Ú¤ÊË). ¢ÈÂÎfiË Ë ¯ÔÚ‹ÁËÛË ¯ÏˆÚÈPaediatriki 2009;72:51-54
Ô‡¯Ô˘ Ó·ÙÚ›Ô˘ Î·È ÙÔ ·È‰› ·Ú·Ì¤ÓÂÈ ·Û˘Ìو̷ÙÈÎfi ÌÂÙ¿ ·fi 6 Ì‹Ó˜.
™˘˙‹ÙËÛË √ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜ Ù‡Ô˘ 1 (PHA 1) Â›Ó·È ÌÈ· Û¿ÓÈ· ÎÏËÚÔÓÔÌÈ΋ ÓfiÛÔ˜ Ô˘ ÂΉËÏÒÓÂÙ·È Ì ·ÒÏÂÈ· Ó·ÙÚ›Ô˘ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, Ì ·ÎfiÏÔ˘ı· ÙËÓ ˘ÔÓ·ÙÚÈ·ÈÌ›·, ˘ÂÚηÏÈ·ÈÌ›·, ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË, ·Ê˘‰¿ÙˆÛË Î·È ·Ó·Ú΋ ·‡ÍËÛË, Ì ·˘ÍË̤ӷ ›‰· ·Ï‰ÔÛÙÂÚfiÓ˘ Î·È ÚÂÓ›Ó˘. √ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜ Ù‡Ô˘ 1 ÂÚÈÁÚ¿ÊËΠÁÈ· ÚÒÙË ÊÔÚ¿ ·fi ÙÔ˘˜ Cheek Î·È Perry ÙÔ 1958 (1). ∆Ô ‚Ú¤ÊÔ˜ ‚ÂÏÙÈÒıËΠı·̷ÙÈο Ì ÙË ¯ÔÚ‹ÁËÛË ¯ÏˆÚÈÔ‡¯Ô˘ Ó·ÙÚ›Ô˘ ·fi ÙÔ ÛÙfiÌ· ÁÈ· ¤Ó· ¤ÙÔ˜. √È Armanini Î·È Û˘Ó. ÌÂϤÙËÛ·Ó ÙËÓ ÎÏÈÓÈ΋ ÔÚ›· ÙÔ˘ ·ÓˆÙ¤Úˆ ·ÛıÂÓÔ‡˜ ÛÙËÓ ËÏÈΛ· ÙˆÓ 28 ÂÙÒÓ, ηıÒ˜ Î·È ‰‡Ô Ӥ˜ ÂÚÈÙÒÛÂȘ ·‰ÂÚÊÒÓ (8 Î·È 2 ÂÙÒÓ) Ì ·ÚfiÌÔÈ· Û˘Ìو̷ÙÔÏÔÁ›·. ∏ ·Ó¿Ï˘ÛË ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ ÙˆÓ ·ÓˆÙ¤Úˆ ·ÛıÂÓÒÓ ¤‰ÂÈÍ ¤Ó· ¤ÏÏÂÈÌÌ· ÛÙÔÓ ˘Ô‰Ô¯¤· ÙˆÓ ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ. ™ÙȘ ·Ú·¿Óˆ ÂÚÈÙÒÛÂȘ, ÔÈ ÁÔÓ›˜ ‹Ù·Ó ·Û˘Ìو̷ÙÈÎÔ› (1,8). ¢È·ÎÚ›ÓÔÓÙ·È ‰‡Ô ÌÔÚʤ˜ ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ˘ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Ù‡Ô˘ 1: Ë ·˘ÙÔۈ̷ÙÈ΋ ÂÈÎÚ·ÙËÙÈ΋ ÌÔÚÊ‹ (adPHA 1, ÓÂÊÚÈ΋ ÌÔÚÊ‹) Î·È Ë ·˘ÙÔۈ̷ÙÈ΋ ˘ÔÏÂÈfiÌÂÓË ÌÔÚÊ‹ (arPHA 1, ÔÏ˘Û˘ÛÙËÌ·ÙÈ΋ ÌÔÚÊ‹) (3-6). ∏ ÌÔÚÊ‹ Ô˘ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙËÙÈÎfi ÙÚfiÔ ÔÊ›ÏÂÙ·È Û ÂÙÂÚfi˙˘Á˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ Ô˘ Έ‰ÈÎÔÔÈ› ÙÔÓ ˘Ô‰Ô¯¤· ÙˆÓ ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ (NR3C2) Ô˘ ·ÊÔÚ¿ ÌfiÓÔ ÙÔ˘˜ ÓÂÊÚÔ‡˜ (4). ∆Ô ÁÔÓ›‰ÈÔ ·˘Ùfi ·ÔÙÂÏÂ›Ù·È ·fi 10 ÂÍfiÓÈ· Î·È ‚Ú›ÛÎÂÙ·È ÛÙÔ ¯ÚˆÌfiۈ̷ 4q31.1. ∏ Û˘Ìو̷ÙÔÏÔÁ›· ÂÌÊ·Ó›˙ÂÙ·È ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, Ì ·ÒÏÂÈ· ¿Ï·ÙÔ˜ ÛÙ· Ô‡Ú·, Â›Ó·È ‹È· Î·È ˘¿Ú¯ÂÈ ·ÓÙ·fiÎÚÈÛË ÛÙËÓ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ¯ÔÚ‹ÁËÛË ¯ÏˆÚÈÔ‡¯Ô˘ Ó·ÙÚ›Ô˘. ™ÙË ÌÔÚÊ‹ ·˘Ù‹, Û˘ÓÈÛÙ¿Ù·È Ë ¯ÔÚ‹ÁËÛË ¯ÏˆÚÈÔ‡¯Ô˘ Ó·ÙÚ›Ô˘ ·fi ÙÔ ÛÙfiÌ·, Ô˘ ÌÔÚ› Ó· ‰È·ÎÔ› ÌÂÙ¿ ·fi 1 ¤ˆ˜ 3 ¯ÚfiÓÈ· ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·È‰È΋˜ ËÏÈΛ·˜, ηıÒ˜ Ë Î·Ù¿ÛÙ·ÛË ‚ÂÏÙÈÒÓÂÙ·È. ∏ ·ÔηٿÛÙ·ÛË ·˘Ù‹ Û˘Ì‚·›ÓÂÈ Ì Ì˯·ÓÈÛÌÔ‡˜ Ô˘ ‰ÂÓ Â›Ó·È Ï‹Úˆ˜ ηٷÓÔËÙÔ›. ¶Èı·ÓÔÏÔÁÂ›Ù·È ·˘ÍË̤ÓË Â·Ó·ÚÚfiÊËÛË Ó·ÙÚ›Ô˘ ÛÙ· ¿ˆ ÂÛÂÈڷ̤ӷ ÛˆÏËÓ¿ÚÈ· ‹ ·Ô‰›‰ÂÙ·È Û ̷ÎÚÔ¯ÚfiÓÈ· ˘ÂÚÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ÚÂÓ›Ó˘-·ÁÁÂÈÔÙ·Û›Ó˘·Ï‰ÔÛÙÂÚfiÓ˘ (1). √ Ù‡Ô˜ ·˘Ùfi˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ˆ˜ ‹È· ÌÔÚÊ‹, ÁÈ·Ù› Ë Û˘Ìو̷ÙÔÏÔÁ›· ˘Ô¯ˆÚ› ÛÙËÓ ÂÓ‹ÏÈÎË ˙ˆ‹, ·ÚfiÏÔ Ô˘ ÔÈ ÙÈ̤˜ ÚÂÓ›Ó˘ Î·È ·Ï‰ÔÛÙÂÚfiÓ˘ ÌÔÚ› Ó· ·Ú·Ì¤ÓÔ˘Ó ˘„ËϤ˜ (3,6,7). ∏ ·˘ÙÔۈ̷ÙÈ΋ ˘ÔÏÂÈfiÌÂÓË ÌÔÚÊ‹ ÔÊ›ÏÂÙ·È Û ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙÔ˘˜ ¢·›ÛıËÙÔ˘˜ ÛÙËÓ ·ÌÈÏÔÚ›‰Ë ÂÈıËÏÈ·ÎÔ‡˜ ‰È·‡ÏÔ˘˜ Ó·ÙÚ›Ô˘ (ENaC). √È ÌÂÙ·ÏÏ¿ÍÂȘ Â›Ó·È ÔÌfi˙˘Á˜ ‹
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·53
53
梉ԸԷωÔÛÙÂÚÔÓÈÛÌfi˜ Ù‡Ô˘ 1 Û ‚Ú¤ÊÔ˜
Û‡ÓıÂÙ˜ ÂÙÂÚfi˙˘Á˜ ·ÓÂÓÂÚÁ¤˜ ÛÙ· ÁÔÓ›‰È· SCNN1A, SCNN1B Î·È SCNN1G (4). √È ˘ÔÌÔÓ¿‰Â˜ ·˘Ù¤˜ ÂÎÊÚ¿˙ÔÓÙ·È ÛÙ· ÂÈıËÏȷο ·ÙÙ·Ú· ÙˆÓ ÓÂÊÚÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ, Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ Ô‰Ô‡, ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘, ÙˆÓ ÛÈÂÏÔÁfiÓˆÓ Î·È È‰ÚˆÙÔÔÈÒÓ ·‰¤ÓˆÓ. ∏ ·Ô˘Û›· ·ӷÚÚfiÊËÛ˘ Ó·ÙÚ›Ô˘ ·Ó·ÛÙ¤ÏÏÂÈ ÙË Ê˘ÛÈÔÏÔÁÈ΋ ·¤ÎÎÚÈÛË Î·Ï›Ô˘ Î·È ˘‰ÚÔÁfiÓÔ˘, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ¯·Ú·ÎÙËÚÈÛÙÈ΋ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË Î·È ÙËÓ ÂÈΛӉ˘ÓË ÁÈ· ÙË ˙ˆ‹ ˘ÂÚηÏÈ·ÈÌ›·. ∏ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÂÈıËÏÈ·ÎÒÓ ‰È·‡ÏˆÓ Ó·ÙÚ›Ô˘ ÛÙ· Â͈ÓÂÊÚÈο ÂÈı‹ÏÈ· ÚÔηÏ› ÛÔ‚·Ú‹ ·ÒÏÂÈ· ¿Ï·ÙÔ˜ ‰È·Ì¤ÛÔ˘ ÙÔ˘ ȉÚÒÙ· Î·È ÙÔ˘ ÂÓÙÂÚÈÎÔ‡ ‚ÏÂÓÔÁfiÓÓÔ˘, ηıÒ˜ Î·È ¿ıÚÔÈÛË ˘ÁÚÔ‡ ÛÙȘ ·ÂÚÔÊfiÚ˜ Ô‰Ô‡˜, ÁÂÁÔÓfi˜ Ô˘ Ô‰ËÁ› ÛÂ Û˘¯Ó¤˜ ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡. √È ·ÛıÂÓ›˜ ¤¯Ô˘Ó ·Ó¿ÁÎË ·fi Û˘Ó¯‹ ¯ÔÚ‹ÁËÛË Û˘ÌÏËÚˆÌ¿ÙˆÓ ¿Ï·ÙÔ˜ ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô Ù˘ ÛÔ‚·Ú‹˜ ˘ÂÚηÏÈ·ÈÌ›·˜. ∂ÌÊ·Ó›˙ÂÙ·È Â›Û˘ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· Ì ÂÓÙÔÓfiÙÂÚË Û˘Ìو̷ÙÔÏÔÁ›·, ˘„ËÏ‹ ıÓËÛÈÌfiÙËÙ· Î·È ÂÈ̤ÓÂÈ ÛÙËÓ ÂÓ‹ÏÈÎË ˙ˆ‹ ¯ˆÚ›˜ ȉȷ›ÙÂÚË ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· (5,6). ∞ӷʤÚÔÓÙ·È ÂÚÈÙÒÛÂȘ ÛÔÚ·‰ÈÎo‡ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Ù‡Ô˘ 1 Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‹È· Û˘Ìو̷ÙÔÏÔÁ›·, Ë ÔÔ›· ˘Ô¯ˆÚ› Ì ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘ Î·È ÙËÓ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ¯ÔÚ‹ÁËÛË Ó·ÙÚ›Ô˘ (6,7). ™Ù· ¿ÙÔÌ· ·˘Ù¿ ¤¯Ô˘Ó ‚ÚÂı› ÌÂÌÔӈ̤ÓÔÈ ÔÏ˘ÌÔÚÊÈÛÌÔ› ÛÙÔ ÁÔÓ›‰ÈÔ NR3C2 ‹ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÔÏ˘ÌÔÚÊÈÛÌÔ‡˜ ÛÙÔ ÁÔÓ›‰ÈÔ Ô˘ Έ‰ÈÎÔÔÈ› ÙÔ˘˜ ÂÈıËÏÈ·ÎÔ‡˜ ‰È·‡ÏÔ˘˜ Ó·ÙÚ›Ô˘ (∂¡aC) Ô˘ ÌÔÚ› Ó· ÂËÚ¿ÛÔ˘Ó ·ÚÓËÙÈο ÙËÓ Â·Ó·ÚÚfiÊËÛË ÙÔ˘ Ó·ÙÚ›Ô˘ (3,6,9,10). ∆· ¿ÙÔÌ· ·˘Ù¿ Â›Ó·È ÎÏÈÓÈο ˘ÁÈ‹, fiˆ˜ Î·È Ù· ̤ÏË Ù˘ ˘fiÏÔÈ˘ ÔÈÎÔÁ¤ÓÂÈ·˜ (7,9,10). ∂ÈϤÔÓ, ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Î·È ‰Â˘ÙÂÚÔ·ı›˜ ÌÔÚʤ˜ Ù˘ ÓfiÛÔ˘ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ·ÓˆÌ·ÏÈÒÓ ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡ (1,11). ™ÙÔÓ ·ÛıÂÓ‹ Ì·˜, Ë ‰È¿ÁÓˆÛË ÙÔ˘ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Ù‡Ô˘ 1 Ù¤ıËΠ·fi Ù· ÎÏÈÓÈο Î·È ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù·, ÙËÓ ·Ó¿Ï˘ÛË DNA Î·È ÙÔÓ ·ÔÎÏÂÈÛÌfi ¿ÏÏˆÓ ÓfiÛˆÓ. ™Ù· Û‡Ó‰ÚÔÌ· ÛˆÏËÓ·Úȷ΋˜ ÔͤˆÛ˘ Î·È Bartter ·Ó¢ڛÛÎÂÙ·È ˘ÔηÏÈ·ÈÌ›· Î·È ˘ÂڷωÔÛÙÂÚÔÓÈÛÌfi˜. √È ‰È·Ù·Ú·¯¤˜ Ù˘ ÛÙÂÚÔÂȉÔÁ¤ÓÂÛ˘ ηÈ, ΢ڛˆ˜, Ë ·Ó¿ÚÎÂÈ· Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ ·ÔÎÏ›ÛÙËÎ·Ó ·fi ÙȘ Ê˘ÛÈÔÏÔÁÈΤ˜ ÙÈ̤˜ Ù˘ ÎÔÚÙÈ˙fiÏ˘, ACTH Î·È 17-OH ÚÔÁÂÛÙÂÚfiÓ˘. √ ÂÎÏÂÎÙÈÎfi˜ ˘Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜ Ô˘ Ú¤ÂÈ Ó· Ù›ıÂÙ·È ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ‚ÚÂÊÒÓ Ì ˘ÂÚηÏÈ·ÈÌ›· Î·È ·ÒÏÂÈ· ¿Ï·ÙÔ˜ ·ÔÎÏ›ÛÙËΠÛÙË Û˘Ó¤¯ÂÈ· ÏfiÁˆ Ù˘ ·˘ÍË̤Ó˘ ÙÈÌ‹˜ ·Ï‰ÔÛÙÂÚfiÓ˘ Ï¿ÛÌ·ÙÔ˜. √ ˘ÔÚÂÓÈÓ·ÈÌÈÎfi˜ ˘Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜, ¿ÏÏË Ì›· ·ÈÙ›· ˘ÂÚηÏÈ·ÈÌ›·˜, ·ÔÎÏ›ÛÙËΠÏfiÁˆ ÙˆÓ ·˘ÍËÌ¤ÓˆÓ ÙÈÌÒÓ Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Î·È ÚÂÓ›Ó˘. ™ÙÔÓ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi
¶›Ó·Î·˜ 1. ∞ÍÈÔÏfiÁËÛË ÙˆÓ ÙÈÌÒÓ ÚÂÓ›Ó˘ Î·È ·Ï‰ÔÛÙÂÚfiÓ˘ Û ÓÂÔÁÓ¿ Î·È ‚Ú¤ÊË Ì ˘ÂÚηÏÈ·ÈÌ›· (11) ƒÂÓ›ÓË ∞ωÔÛÙÂÚfiÓË æ¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÈÓÈÛÌfi˜ (æÀ∞) Ù‡Ô˘ 1 Î·È ·ÚÔ‰ÈÎfi˜ æÀ∞ ÀԷωÔÛÙÂÚÔÓÈÛÌfi˜ 梉ԸԷωÔÛÙÂÚÈÓÈÛÌfi˜ (æÀ∞) Ù‡Ô˘ 2 ÀÔÚÂÓÈÓ·ÈÌÈÎfi˜ ˘Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜
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Ù‡Ô˘ 2 ‰ÂÓ ˘¿Ú¯ÂÈ ˘ÔÓ·ÙÚÈ·ÈÌ›· Î·È Ù· ›‰· ÚÂÓ›Ó˘ Â›Ó·È ¯·ÌËÏ¿, ÂÓÒ Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ Â›Ó·È ˘„ËÏ¿ ‹ Ê˘ÛÈÔÏÔÁÈο (¶›Ó·Î·˜ 1) (11,12). ∏ ı·̷ÙÈ΋ ·ÓÙ·fiÎÚÈÛË ÛÙË ¯ÔÚ‹ÁËÛË ¯ÏˆÚÈÔ‡¯Ô˘ Ó·ÙÚ›Ô˘ Î·È Ë ÔÚ›· ÙÔ˘ ·ÛıÂÓÔ‡˜ ‹Ù·Ó ÂÓ‰ÂÈÎÙÈο ‹È·˜ ÌÔÚÊ‹˜ Ù˘ ÓfiÛÔ˘. √ ÁÔÓȉȷÎfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍ ÙÚÂȘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡˜ ÛÙÔ ÂÍfiÓÈÔ 2, ηı¤Ó·˜ ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ·ÓÂÍ¿ÚÙËÙ· Âȉڿ ÂÏ¿¯ÈÛÙ· ÛÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ˘Ô‰Ô¯¤· ÙˆÓ ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ (MR), ·ÏÏ¿ ÌÂϤÙ˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Ô Û˘Ó‰˘·ÛÌfi˜ ‰‡Ô ‹ ·Ú·¿Óˆ Ù¤ÙÔÈˆÓ ÔÏ˘ÌÔÚÊÈÛÌÒÓ ÌÔÚ› Ó· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÎÏÈÓÈ΋ ¤ÎÊÚ·ÛË ÙÔ˘ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Ù‡Ô˘ 1 (7,10). ™ÙȘ ̤¯ÚÈ Û‹ÌÂÚ· ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ÔÈÎÔÁÂÓÂÈÒÓ Ì PHA 1 ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ Ì ÙÔÓ ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙËÙÈÎfi ÙÚfiÔ, Ë ·ÓÙ·fiÎÚÈÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÙË ¯ÔÚ‹ÁËÛË ¯ÏˆÚÈÔ‡¯Ô˘ Ó·ÙÚ›Ô˘ ·fi ÙÔ ÛÙfiÌ· ‹Ù·Ó ı·̷ÙÈ΋, ·ÚfiÏÔ Ô˘ ÔÈ ÙÈ̤˜ ·Ï‰ÔÛÙÂÚfiÓ˘ ·Ú·Ì¤ÓÔ˘Ó ˘„ËϤ˜, fiˆ˜ ÛÙÔÓ ‰ÈÎfi Ì·˜ ·ÛıÂÓ‹. ∞fi ÙÔ ÈÛÙÔÚÈÎfi ÙˆÓ ÁÔÓ¤ˆÓ ‰ÂÓ ÚÔ·ÙÂÈ ¿ÓÙÔÙ οÔÈÔ ÛÙÔÈ¯Â›Ô ·Ó¿ÏÔÁ˘ Û˘Ìو̷ÙÔÏÔÁ›·˜, ÂÓÒ ÌÂÚÈΤ˜ ÊÔÚ¤˜ Ô ¤Ó·˜ ·fi ÙÔ˘˜ ‰‡Ô ÁÔÓ›˜ ›¯Â ÚÔ‚Ï‹Ì·Ù· Û›ÙÈÛ˘ Î·È ·Ó·ÚÎÔ‡˜ ·Ó¿Ù˘Í˘ ÛÙË ‚ÚÂÊÈ΋ ÙÔ˘ ËÏÈΛ·, Ô˘ ÍÂÂÚ¿ÛÙËÎ·Ó ¯ˆÚ›˜ ıÂڷ›·. ∆· ›‰· ·Ï‰ÔÛÙÂÚfiÓ˘ ÙˆÓ ÁÔÓ¤ˆÓ ÌÔÚ› Ó· ‚ÚÂıÔ‡Ó ˘„ËÏ¿, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ·Ó ·ÚÔ˘Û›·Û·Ó Û˘ÌÙÒÌ·Ù· ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ·, ÂÓÒ Ù· ›‰· ÚÂÓ›Ó˘ Â›Ó·È Ê˘ÛÈÔÏÔÁÈο ‹ ·˘ÍË̤ӷ (3,6,7). ™ÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ ‰ÈÎÔ‡ Ì·˜ ·ÛıÂÓÔ‡˜, Ë ÌËÙ¤Ú· ›¯Â Û˘Ìو̷ÙÔÏÔÁ›· Î·È Ù· ›‰· ·Ï‰ÔÛÙÂÚfiÓ˘ ‹Ù·Ó ˘„ËÏ¿. Œ¯ÂÈ ‚ÚÂı› fiÙÈ ÁÔÓ›˜ Ô˘ ‹Ù·Ó ÊÔÚ›˜ Ù˘ ›‰È·˜ ÌÂÙ¿ÏÏ·Í˘ Ì ÙÔ ·È‰› ÙÔ˘˜, Ì ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙËÙÈÎfi ÙÚfiÔ, ‰ÂÓ ÂΉ‹ÏˆÛ·Ó ÔÙ¤ ÎÏÈÓÈο Û˘ÌÙÒÌ·Ù·, ·ÚfiÏÔ Ô˘ ›¯·Ó ·˘ÍË̤ӷ ›‰· ·Ï‰ÔÛÙÂÚfiÓ˘ (7). ∆Ô ÁÂÁÔÓfi˜ ·˘Ùfi ˘Ô‰ËÏÒÓÂÈ ÙËÓ Èı·ÓfiÙËÙ· ›‰Ú·Û˘ ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ‹ ·ÎfiÌ· ÙËÓ ·ÚÔ˘Û›· ÌÂÙ·ÏÏ¿ÍÂˆÓ Î·È Û ¿ÏÏ· ÁÔÓ›‰È· Ô˘ ‰ÂÓ ¤¯Ô˘Ó ·ÎfiÌË ÌÂÏÂÙËı›. ™Â ·˘Ùfi Û˘ÓËÁÔÚ› Î·È Ë ÂÚÈÁÚ·Ê‹ ÂÚÈÙÒÛÂˆÓ ¶·È‰È·ÙÚÈ΋ 2009;72:51-54
Pediatric Jan-Feb 09
16-03-09
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Ã. ¢·ÛηÏÔÔ‡ÏÔ˘ Î·È Û˘Ó.
„¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Ù‡Ô˘ 1 ‹È·˜ ÌÔÚÊ‹˜ ÛÙȘ Ôԛ˜ ‰ÂÓ ‚Ú¤ıËΠη̛· ÌÂÙ¿ÏÏ·ÍË ÛÙÔ ÁÔÓ›‰ÈÔ NR3C2 Î·È ‰Â›¯ÓÂÈ ÙË ÁÂÓÂÙÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ· ÙÔ˘ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌÔ‡ Ù‡Ô˘ 1 (3,7,13). Œ¯Ô˘Ó ÂÚÈÁÚ·ÊÙ› 22 ·ÓÂÓÂÚÁ¤˜ ÌÂÙ·ÏÏ¿ÍÂȘ ·˘ÙÔ‡ ÙÔ˘ ÁÔÓȉ›Ô˘ (6). ™ÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ ‰ÈÎÔ‡ Ì·˜ ·ÛıÂÓÔ‡˜ ‰ÂÓ ¤ÁÈÓ ÁÔÓȉȷÎfi˜ ¤ÏÂÁ¯Ô˜ ÙˆÓ ÁÔÓ¤ˆÓ. ™˘ÌÂÚ·ÛÌ·ÙÈο, fiÙ·Ó Ô ·È‰›·ÙÚÔ˜ ·ÓÙÈÌÂÙˆ›˙ÂÈ ÓÂÔÁÓ¿ ‹ ÌÈÎÚ¿ ‚Ú¤ÊË Ì ·Ó·Ú΋ ÚfiÛÏË„Ë ‚¿ÚÔ˘˜, ·Ê˘‰¿ÙˆÛË, ˘ÔÓ·ÙÚÈ·ÈÌ›·, ˘ÂÚηÏÈ·ÈÌ›·, Ô˘ ·ÔÙÂÏÔ‡Ó ÎÏÈÓÈο Â˘Ú‹Ì·Ù· ÎÔÈÓ¿ Û ÔÏÏ¿ ·È‰È·ÙÚÈο ÓÔÛ‹Ì·Ù·, ı· Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÈ ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔÓ „¢‰Ô¸Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi Ù‡Ô˘ 1, ΢ڛˆ˜ fiÙ·Ó Û˘Ó‰˘¿˙ÔÓÙ·È Ì ÓÂÊÚÈ΋ ·ÒÏÂÈ· ¿Ï·ÙÔ˜ Î·È ¤¯ÂÈ ·ÔÎÏÂÈÛÙ› Ë Û˘ÁÁÂÓ‹˜ ˘ÂÚÏ·Û›· ÂÈÓÂÊÚȉ›ˆÓ.
µÈ‚ÏÈÔÁÚ·Ê›· 1. Proctor G, Linas S. Type 2 Pseudohypoaldosteronism: new insights into renal potassium, sodium, and chloride handling. Am J of Kidney Dis 2006;48:674-693. 2. Rodriguez-Soriano J. Tubular disorders of electrolyte regulation. In: Holiday M, Barrat M, Anver E, editors. Pediatric nephrology. Baltimore: Williams and Wilkins; 1994. p. 631-632. 3. Viemann M, Peter M, Lopez-Siguero JP, Simic-Schleicher G, Sippel GW. Evidence for genetic heterogeneity of pseudohypoaldosteronism type 1: Identification of a novel mutation in the human mineralocorticoid receptor in one sporadic case and no mutation in two autosomal dominant kindrends. J Clin Endocrinol Metab 2001;86:2056-2059. 4. Riepe GF, Finkeldei J, Sanctis L, Einaudi S, Testa A, Karges B, et al. Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. J of Clin Endocrinol and Metab 2006;91:4552-4561.
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5. Geller D, Zhang J, Zennaro M, Vallo-Boado A, RodriguezSoriano J, Furu L, et al. Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for neonatal lethality and phenotypic expression in adults. J Am Soc Nephrol 2006;17:1429-1436. 6. Fernandes-Rosa F, Castro M, Latronico AC, Sippel W, Riepe FG, Antonini S. Recurrence of the R947X mutation in unrelated families with autosomal dominant pseudohypoaldosteronism type 1: evidence for a mutational hot spot in the mineralocorticoid receptor gene. J of Clinic Endocrinol and Metab 2006;91:3671-3675. 7. Balsamo A, Cicognari A, Gennari M, Sippell W, Menabo S, Baronio F et al. Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosterinism type 1. Eur J of Endocrinol 2007;156:249-256. 8. Armanini D, Kuhnle U, Strasser T, Dorr H, Butenandt I, Weber P, et al. Aldosterone-receptor deficiency in pseudohypoaldosteronism. N Engl J Med 1985;313:1178-1181. 9. Arai K, Zachman K, Tamotsu S, Chrousos GP. Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: Do they have pathologic potential? J of Clin Endocrinol and Metab 1999;84:2434-2437. 10. Arai K, Nakagomi Y, Iketami M, Shimura Y, Amemiya S, Ohyama K, et al. Functional polymorphisms in the mineralocorticoid receptor and amirolide-sensitive sodium channel genes in a patient with sporadic pseudohypoaldosteronism. Hum Genet 2003;112:91-97. 11. Giapros VI, Tsatsoulis AA, Drougia EE, Kollios KD, Siomou EC, Andronikou SK. Rare causes of acute hyperkalemia in the 1st week of life - Three case reports. Pediatr Nephrol 2004;19:1046-1049. 12. Forest M. Adrenal steroid deficiency states. In: Brook C, editor. Clinical pediatric endocrinology. London: Blackwell; 1989. p. 389-390. 13. Riepe F, Holterhus PM. Exclusion of serum and glucocorticoid induced kinase (SGK1) as a candidate gene for genetically heterogeneous renal pseudohypoaldosteronism type 1 in eight families. Am J Nephr 2007;27:164-169.
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∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏
CASE REPORT
55
π‰ÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË Û Ó·ÚÔ‡˜ ÂÊ‹‚Ô˘˜ Ì ·¯˘Û·ÚΛ· ∞. ºÈÏÈ›‰ËÅ, ™. ™ÙÂÊ·Ó¿ÎËÅ, ª. ∞Ó·ÙÔÏȈٿÎËÅ, °. µÏ·¯¿ÎËÅ, Ã. º·ÓÔ˘ÚÈ¿Î˘Ç, ∞. ∆ÛÈÏÈÌÈÁοÎËÅ ¶ÂÚ›ÏË„Ë: ∏ ȉÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË ‹ „¢‰ofiÁÎÔ˜ ÂÁÎÂÊ¿ÏÔ˘ ÂÌÊ·Ó›˙ÂÙ·È Û fiϘ ÙȘ ËÏÈ˘, ·ÏÏ¿ Â›Ó·È Û˘¯ÓfiÙÂÚË Û ·¯‡Û·ÚΘ Á˘Ó·›Î˜ ·Ó··Ú·ÁˆÁÈ΋˜ ËÏÈΛ·˜. ™ÙÔÓ ·È‰È·ÙÚÈÎfi ÏËı˘ÛÌfi ÂÌÊ·Ó›˙ÂÙ·È ·fi ÙË ‚ÚÂÊÈ΋ ¤ˆ˜ Î·È ÙËÓ ÂÊË‚È΋ ËÏÈΛ·, Ì ÌÂÁ·Ï‡ÙÂÚË Â›ÙˆÛË Û ·¯‡Û·ÚÎÔ˘˜ ÂÊ‹‚Ô˘˜. ∆· Û˘Ó‹ıË Û˘ÌÙÒÌ·Ù· Ù˘ ÓfiÛÔ˘ Â›Ó·È ÎÂÊ·Ï·ÏÁ›·, Ó·˘Ù›·, ¤ÌÂÙÔÈ Î·È ÔÊı·ÏÌÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜. ¶ÂÚÈÁÚ¿ÊÔÓÙ·È Ù¤ÛÛÂÚȘ ÂÚÈÙÒÛÂȘ ·¯‡Û·ÚÎˆÓ ‹ ˘¤Ú‚·ÚˆÓ Ó·ÚÒÓ ÂÊ‹‚ˆÓ, ËÏÈΛ·˜ ‰Ò‰Âη ¤ˆ˜ ‰ÂηÙÚÈÒÓ ÂÙÒÓ, Ì ȉÈÔ·ı‹ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË, Ô˘ ÓÔÛËχÙËÎ·Ó ÛÙËÓ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ Ù· ÙÂÏÂ˘Ù·›· ‰‡Ô ¯ÚfiÓÈ·. ∏ ‰È¿ÁÓˆÛË Ù¤ıËΠ̠‚¿ÛË Ù· ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÁÈ· ÙËÓ È‰ÈÔ·ı‹ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË ÛÙ· ·È‰È¿, Ù· ÔÔ›· ‚·Û›˙ÔÓÙ·È ÛÙ· ÙÚÔÔÈË̤ӷ ÎÚÈÙ‹ÚÈ· Dandy ÁÈ· ÂÓ‹ÏÈΘ. T· ·ÚÈ· Û˘ÌÙÒÌ·Ù· ‹Ù·Ó Ë ‰Èψ›· Î·È Ë ÎÂÊ·Ï·ÏÁ›·. ŸÏ· Ù· ·È‰È¿ Ô˘ ÌÂÏÂÙ‹ıËÎ·Ó Â›¯·Ó BMI ÌÂÁ·Ï‡ÙÂÚÔ ·fi ÙËÓ ÂÓÂÓËÎÔÛÙ‹ (90‹) ÂηÙÔÛÙÈ·›· ı¤ÛË ÁÈ· ÙËÓ ËÏÈΛ· ÙÔ˘˜. ™Â fiϘ ÙȘ ÂÚÈÙÒÛÂȘ ‰È·ÈÛÙÒıËΠԛ‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ. ∆Ô ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi ›¯Â ·˘ÍË̤ÓË ›ÂÛË Î·È ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋˜ Û‡ÛÙ·Û˘. √ Ó¢ÚÔ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ Ì ̷ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ ‰ÂÓ ·Ó¤‰ÂÈÍ ¯ˆÚÔηٷÎÙËÙÈ΋ ÂÍÂÚÁ·Û›·, ‰È¿Ù·ÛË ÙˆÓ ÎÔÈÏÈÒÓ ‹ ÊÏ‚È΋ ·ÔÊÚ·ÎÙÈ΋ ÓfiÛÔ. ∏ Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ Ì ·ÎÂÙ·˙ÔÏ·Ì›‰Ë ‹Ù·Ó ·ÔÙÂÏÂÛÌ·ÙÈ΋ Û fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜. ŒÓ· ¤ˆ˜ ‰‡Ô ¯ÚfiÓÈ· ÌÂÙ¿, ÔÈ ¤ÊË‚ÔÈ ·Ú·Ì¤ÓÔ˘Ó ·Û˘Ìو̷ÙÈÎÔ›. ∏ ·¯˘Û·ÚΛ· Û Ó·ÚÔ‡˜ ÂÊ‹‚Ô˘˜ ıˆÚÂ›Ù·È ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÔÏϤ˜ ÓÔÛËÚ¤˜ ηٷÛÙ¿ÛÂȘ, fiˆ˜ Ë È‰ÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË.
1 ∞’ Î·È µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, µÂÓÈ˙¤ÏÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ 2 √Êı·ÏÌÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, µÂÓÈ˙¤ÏÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ AÏÏËÏÔÁÚ·Ê›·: ∞Ì·Ï›· ∆ÛÈÏÈÌÈÁοÎË tsilimam@yahoo.gr ∏ÚÔ‰fiÙÔ˘ 214, ∆.∫. 71601, ¡. ∞ÏÈηÚÓ·ÛÛfi˜, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘
§¤ÍÂȘ ÎÏÂȉȿ: π‰ÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË, ·¯˘Û·ÚΛ·.
Idiopathic intracranial hypertension in young adolescents with obesity A. FilippidiÅ, S. StefanakiÅ, M. AnatoliotakiÅ, G. VlachakiÅ, C. FanouriakisÇ, A. TsilimigakiÅ Abstract: Idiopathic intracranial hypertension or pseudotumor cerebri appears at all ages, but it is most frequent in obese women of childbearing age. πn the paediatric population it appears from infancy to puberty, with a high incidence among obese adolescents. ∏eadache, nausea, vomiting, and ophthalmological abnormalities are common symptoms of the disease. The cases are reported of four obese or overweight young adolescents, aged 12 to 13 years, with idiopathic intracranial hypertension newly diagnosed during the last two years. The diagnosis was based on the diagnostic criteria of idiopathic intracranial hypertension for children, which were developed from the modified Dandy criteria for adults. The main symptoms were diplopia and headache. All children had body mass index (BMI) >90th percentile for age, and papilloedema was found in all cases. ∆he cerebrospinal fluid (CSF) pressure was increased and the CSF composition was normal. Neuroimaging study with magnetic resonance imaging (MRI) of the brain showed no intracranial mass lesion, ventricular dilation or venous obstructive disease. The treatment with acetazolamide was effective and all four adolescents remain asymptomatic one and two years later. Obesity in young adolescents is considered to be a risk factor for a variety of medical conditions, including idiopathic intracranial hypertension.
1 1st and 2nd Departments of Paediatrics, "Venizelio" General Hospital, Heraklion, Crete, Greece 2 Department of Ophthalmology, “Venizelio” General Hospital, Heraklion, Crete, Greece Correspondence: Amalia Tsilimigaki tsilimam@yahoo.gr 214, Irodotou St., ¡. Alikarnassos, 71601, Heraklion, Crete, Greece
Key words: Idiopathic intracranial hypertension, obesity.
™˘ÓÙÔÌÔÁڷʛ˜: π∂À √¡¶
ȉÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË ÔÛÊ˘ÔÓˆÙÈ·›· ·Ú·Î¤ÓÙËÛË
∂ÈÛ·ÁˆÁ‹ ∏ ȉÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË (π∂À) ‹ „¢‰ÔfiÁÎÔ˜ ÂÁÎÂÊ¿ÏÔ˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·˘ÍË̤ÓË ÂÓ‰ÔÎÚ¿ÓÈ· ›ÂÛË, Ë ÔÔ›· ‰ÂÓ ÔÊ›-
ÏÂÙ·È Û ˘‰ÚÔΤʷÏÔ ‹ ¯ˆÚÔηٷÎÙËÙÈ΋ ÂÍÂÚÁ·Û›· (1,2). ∆Ô ∂¡À ¤¯ÂÈ Ê˘ÛÈÔÏÔÁÈ΋ Û‡ÛÙ·ÛË Î·È ÔÈ ÎÔÈϛ˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ Â›Ó·È Ê˘ÛÈÔÏÔÁÈΤ˜ (3). ∏ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È Ì ‚¿ÛË Ù· ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÁÈ· ÙËÓ È‰ÈÔ·ı‹ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË ÛÙ· ·È‰È¿ (4) (¶›Ó·Î·˜ 1), Ù· ÔÔ›· ‚·Û›˙ÔÓÙ·È ÛÙ· ÙÚÔÔÔÈË̤ӷ ÎÚÈÙ‹ÚÈ· Dandy. ∆· Û˘Ó‹ıË Û˘ÌÙÒÌ·Ù· Ù˘ ÓfiÛÔ˘ ¶·È‰È·ÙÚÈ΋ 2009;72:55-59
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·56
56
∞. ºÈÏÈ›‰Ë Î·È Û˘Ó.
Â›Ó·È ÎÂÊ·Ï·ÏÁ›·, Ó·˘Ù›·, ¤ÌÂÙÔÈ Î·È ÔÊı·ÏÌÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ ¤ˆ˜ Î·È ·ÒÏÂÈ· fiÚ·Û˘ (4-8). ∏ ·¯˘Û·ÚΛ· ıˆÚÂ›Ù·È ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· π∂À ÛÙÔ˘˜ ÂÓ‹ÏÈΘ, ȉȷ›ÙÂÚ· Û ·¯‡Û·ÚΘ Á˘Ó·›Î˜ ·Ó··Ú·ÁˆÁÈ΋˜ ËÏÈΛ·˜ (1,9,10). ™ÙÔÓ ·È‰È·ÙÚÈÎfi ÏËı˘ÛÌfi, Ë π∂À ‰ÂÓ Ê·›ÓÂÙ·È Ó· ÂÌÊ·Ó›˙ÂÙ·È Û˘¯ÓfiÙÂÚ· Û ·¯‡Û·Úη ·È‰È¿ ÚÈÓ ÙËÓ ‹‚Ë. øÛÙfiÛÔ, fiÛÔ ·˘Í¿ÓÂÈ Ë ËÏÈΛ· ÙÔ˘ ·È‰ÈÔ‡, ˘¿Ú¯ÂÈ ÌÂÁ·Ï‡ÙÂÚË Û˘Û¯¤ÙÈÛË ·¯˘Û·ÚΛ·˜ Î·È π∂À Î·È ÛÙËÓ ÂÚ›Ô‰Ô Ù˘ ÂÊ˂›·˜ Êı¿ÓÂÈ Ù· ÔÛÔÛÙ¿ ÙˆÓ ÂÓËÏ›ÎˆÓ (2). √ ÂÈÔÏ·ÛÌfi˜ Ù˘ ·¯˘Û·ÚΛ·˜ ¤¯ÂÈ Û¯Â‰fiÓ ‰ÈÏ·ÛÈ·ÛÙ› ÙȘ ‰‡Ô ÙÂÏÂ˘Ù·›Â˜ ‰ÂηÂٛ˜ ÛÙȘ ∏¶∞ Î·È ÛÙËÓ ∂˘ÚÒË, ·ÎÔÏÔ˘ıÒÓÙ·˜ ·Ú¿ÏÏËÏË ÔÚ›· Ì ÙËÓ ·˘ÍË̤ÓË Â›ÙˆÛË Ù˘ π∂À (11). ∞ÎÔÏÔ˘ı› ÂÚÈÁÚ·Ê‹ 4 ÂÚÈÙÒÛÂˆÓ ·¯‡Û·ÚÎˆÓ ‹ ˘¤Ú‚·ÚˆÓ ÂÊ‹‚ˆÓ Ì π∂À, Ô˘ ÓÔÛËχÙËÎ·Ó ÛÙËÓ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ Ù· ÙÂÏÂ˘Ù·›· 2 ¯ÚfiÓÈ·.
¶ÚÒÙË ÂÚ›ÙˆÛË ∞ÁfiÚÈ, ËÏÈΛ·˜ 13 ÂÙÒÓ, ÚÔÛ‹Ïı ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÏfiÁˆ ·Ó·ÊÂÚfiÌÂÓˆÓ ÂÂÈÛÔ‰›ˆÓ ·ÚÔ‰È΋˜ ‰Èψ›·˜ ·fi 10Ë̤ÚÔ˘ Î·È ·˘¯ÂÓ·ÏÁ›·˜. ∆Ô ·È‰› ‹Ù·Ó ˘fi ·Ú·ÎÔÏÔ‡ıËÛË ÛÙÔ È·ÙÚÂ›Ô ·¯˘Û·ÚΛ·˜ Ù˘ ÎÏÈÓÈ΋˜ Ì·˜ ·fi ¤ÙÔ˘˜. ∞fi ÙÔ ÚfiÛÊ·ÙÔ ·ÙÔÌÈÎfi ·Ó·ÌÓËÛÙÈÎfi ·Ó·Ê¤ÚÂÙ·È Ï‹„Ë ÛÂÙÈÚÈ˙›Ó˘, ÚÈÓ 15 Ë̤Ú˜, ÏfiÁˆ ÎÓ›‰ˆÛ˘. ∆Ô ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ‹Ù·Ó ÂχıÂÚÔ. ∆Ô ·È‰› ‹Ù·Ó ·‡ÚÂÙÔ Î·È Ë Ó¢ÚÔÏÔÁÈ΋ ÂͤٷÛË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋. ∞fi Ù· ˘fiÏÔÈ· Û˘ÛÙ‹Ì·Ù· ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∞¶ = 111/74 mmHg, ÛÊ›ÍÂȘ = 61/min. ∆· ۈ̷ÙÔÌÂÙÚÈο ÛÙÔȯ›· ‹Ù·Ó: µ™ = 85 kg (>97Ë ∂£), À™ = 161 cm (50‹-75Ë ∂£), BMI = 32,8 (>97Ë ∂£). ¶ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ = 119 cm (>95Ë ∂£) (12). ™Ù¿‰ÈÔ Tanner ÁÂÓÓËÙÈο fiÚÁ·Ó· Î·È ÂÊ‹‚·ÈÔ πππ. ∞fi ÙËÓ ÔÊı·ÏÌÔÏÔÁÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËÎÂ: Ô›‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ, Ì ·Û¿ÊÂÈ· ÙˆÓ ÔÚ›ˆÓ ÙÔ˘ ÔÙÈÎÔ‡ Ó‡ÚÔ˘, ÂÍȉڈ̷ÙÈο ÛÙÔȯ›· ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ Ô›ÛıÈÔ˘ fiÏÔ˘, ηıÒ˜ ›Û˘ Î·È ÌÈÎÚÔ·ÈÌÔÚÚ·Á›Â˜ ‰ÂÍÈÔ‡ Î·È ·ÚÈÛÙÂÚÔ‡ ÔÊı·ÏÌÔ‡. ∂›Û˘, ÛËÌÂÈÒıËΠ·‰˘Ó·Ì›· ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÊÏ‚ÈÎÔ‡ ÛÊ˘ÁÌÔ‡. ∞fi ÙËÓ ÂͤٷÛË ÙˆÓ ÔÙÈÎÒÓ Â‰›ˆÓ ‰È·ÈÛÙÒıËΠ‰È‡ڢÓÛË Ù˘ÊÏ‹˜ ÎËÏ›‰·˜ ·ÌÊfiÙÂÚˆÓ ÙˆÓ ÔÊı·ÏÌÒÓ. ∏ ÔÙÈ΋ Ô͇ÙËÙ·, Ù· ÚfiÛıÈ· ÌfiÚÈ·, Ô ÎÂÚ·ÙÔÂȉ‹˜ Î·È Ù· ·ÓÙ·Ó·ÎÏ·ÛÙÈο Ù˘ ÎfiÚ˘ ‹Ù·Ó ηٿ ʇÛË. ∂Ï‹ÊıË Ï‹Ú˘ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ (ÁÂÓÈ΋ ·›Ì·ÙÔ˜, ‚ÈÔ¯ËÌÈÎfi˜ ¤ÏÂÁ¯Ô˜, ÁÂÓÈ΋ Ô‡ÚˆÓ, ÏÈ›‰È·, ÏÈÔÚˆÙ½Ó˜, ÔÚÌfiÓ˜ ı˘ÚÂÔÂȉԇ˜, ACTH, ÎÔÚÙÈ˙fiÏË, ÈÓÛÔ˘Ï›ÓË), Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ∆Ô ·È‰› ˘Ô‚Ï‹ıËΠ۠MRI ÂÁÎÂÊ¿ÏÔ˘, Ô˘ ‰ÂÓ ·Ó¤‰ÂÈÍ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ŒÁÈÓ √¡¶ Ô˘ ¤‰ÂÈÍÂ: ›ÂÛË ∂¡À 870 mm H2O, ÏÂ˘Î¿ = 0/mmÑ, ۿί·ÚÔ Paediatriki 2009;72:55-59
= 78 mg/dl Î·È Ï‡Έ̷ = 20 mg/dl. ªÂÙ¿ ÙËÓ √¡¶, Ô ·ÛıÂÓ‹˜ ‰ÂÓ ·Ó¤ÊÂÚ ϤÔÓ ‰Èψ›·, ÏËÓ 2 ÂÂÈÛÔ‰›ˆÓ ‚Ú·¯Â›·˜ ‰È¿ÚÎÂÈ·˜. ªÂ ÙË ‰È¿ÁÓˆÛË π∂À, Ô ·ÛıÂÓ‹˜ ÂÙ¤ıË Û ıÂڷ›· Ì ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Ì ‰fiÛË 750 mg/24h. ∂Í‹Ïı ÌÂÙ¿ ·fi 6 Ë̤Ú˜ ÓÔÛËÏ›·˜, Ì ʷÚ̷΢ÙÈ΋ ·ÁˆÁ‹ ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Î·È Î¿ÏÈÔ. ™˘ÓÂÛÙ‹ıË Ù·ÎÙÈ΋ ÔÊı·ÏÌÔÏÔÁÈ΋ ÂÎÙ›ÌËÛË Î·È ‰fiıËÎ·Ó Ô‰ËÁ›Â˜ ‰È·ÙÚÔÊ‹˜ ÁÈ· ·ÒÏÂÈ· ‚¿ÚÔ˘˜. ªÂÙ¿ ·fi 2 Ì‹Ó˜, ÙÔ Ô›‰ËÌ· ÙˆÓ ÔÙÈÎÒÓ ıËÏÒÓ ˘Ô¯ÒÚËÛÂ Î·È ‰ÈÂÎfiË Ë ıÂڷ›·. ∆Ô ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ›¯Â ÂÏ·ÙÙˆı› ηٿ 4 kg. ¢‡Ô ¯ÚfiÓÈ· ÌÂÙ¿, ÙÔ ·È‰› Â›Ó·È ·Û˘Ìو̷ÙÈÎfi, Ì ÂÏ·Ùو̤ÓÔ ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ Î·È Û ηϋ ÁÂÓÈ΋ ηٿÛÙ·ÛË.
¢Â‡ÙÂÚË ÂÚ›ÙˆÛË ∫ÔÚ›ÙÛÈ, ËÏÈΛ·˜ 13 ÂÙÒÓ, ÚÔÛ‹Ïı ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÏfiÁˆ ‰Èψ›·˜ Î·È ÂÌ¤ÙˆÓ ·fi 24ÒÚÔ˘, ηıÒ˜ Î·È ÎÂÊ·Ï·ÏÁ›·˜ ·fi 15Ë̤ÚÔ˘. ∆Ô ·È‰› ‹Ù·Ó ·‡ÚÂÙo Î·È Ë Ó¢ÚÔÏÔÁÈ΋ ÂͤٷÛË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋. ∞¶ = 120/63 mmHg, ÛÊ›ÍÂȘ = 75/min. ∆· ۈ̷ÙÔÌÂÙÚÈο ÙÔ˘ ÛÙÔȯ›· ‹Ù·Ó: µ™ = 69 kg (90‹-97Ë ∂£), À™ = 157 cm (50‹ ∂£), BMI = 28 (90‹-97Ë ∂£). ¶ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ = 95 cm (>95Ë ∂£) (12). ™Ù¿‰ÈÔ Tanner ÛÙ‹ıÔ˜ Î·È ÂÊ‹‚·ÈÔ πππ. ∞fi ÙËÓ ÔÊı·ÏÌÔÏÔÁÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠԛ‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ, Ì ·ÈÌÔÚÚ·ÁÈο ÛÙÔȯ›· ¿Ìʈ. ∏ ÔÙÈ΋ Ô͇ÙËÙ·, Ù· ÚfiÛıÈ· ÌfiÚÈ·, Ô ÎÂÚ·ÙÔÂȉ‹˜ Î·È Ù· ·ÓÙ·Ó·ÎÏ·ÛÙÈο Ù˘ ÎfiÚ˘ ‹Ù·Ó ηٿ ʇÛË. ∂Ï‹ÊıË Ï‹Ú˘ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜, Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ŒÁÈÓ MRI ÂÁÎÂÊ¿ÏÔ˘, Ë ÔÔ›· ¤‰ÂÈÍ ÂÏ·ÊÚ¿ ‰È‡ڢÓÛË ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ˘·Ú·¯ÓÔÂȉԇ˜ ¯ÒÚÔ˘, ¯ˆÚ›˜ ÛËÌ›· ˘‰ÚÔÎÂÊ¿ÏÔ˘ ‹ ¯ˆÚÔηٷÎÙËÙÈ΋˜ ‚Ï¿‚˘. ∏ √¡¶ ¤‰ÂÈÍÂ: ›ÂÛË ∂¡À = 420 mm H2O, ÏÂ˘Î¿ = 3/mmÑ, ۿί·ÚÔ = 68 mg/dl Î·È Ï‡Έ̷ = 22,5 mg/dl. ∏ ·ÛıÂÓ‹˜ ÂÙ¤ıË Û ıÂڷ›· Ì ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Ì ‰fiÛË 500 mg/24h Î·È ·ÚÔ˘Û›·Û ‡ÊÂÛË ÙˆÓ Û˘Ìو̿وÓ. ∆Ô 8Ô 24ˆÚÔ ÓÔÛËÏ›·˜ ˘‹ÚÍ ۷ʋ˜ ‚ÂÏÙ›ˆÛË Ù˘ ÂÈÎfiÓ·˜ ÙˆÓ ÔÙÈÎÒÓ ıËÏÒÓ, Ì ·ÔÚÚfiÊËÛË ÙˆÓ ·ÈÌÔÚÚ·ÁÈÒÓ. ∏ ·ÛıÂÓ‹˜ ÂÍ‹Ïı Ì ·ÁˆÁ‹ ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Î·È ‰È·ÈÙËÙÈΤ˜ Ô‰ËÁ›Â˜ ÁÈ· ·ÒÏÂÈ· ‚¿ÚÔ˘˜. ∆Ô Ô›‰ËÌ· ÙˆÓ ÔÙÈÎÒÓ ıËÏÒÓ ˘Ô¯ÒÚËÛÂ Î·È ‰ÈÂÎfiË Ë ıÂڷ›· 2 Ì‹Ó˜ ÌÂÙ¿. ∆Ô ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ›¯Â ÂÏ·ÙÙˆı› ηٿ 3 kg. ŒÓ· ¯ÚfiÓÔ ÌÂÙ¿, ÙÔ ·È‰› Â›Ó·È ·Û˘Ìو̷ÙÈÎfi. ∆Ú›ÙË ÂÚ›ÙˆÛË ∞ÁfiÚÈ, ËÏÈΛ·˜ 13 ÂÙÒÓ, ÚÔÛ‹Ïı ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÏfiÁˆ ‰Èψ›·˜ ·fi 10Ë̤ÚÔ˘ Î·È ÎÂÊ·Ï·ÏÁ›·˜ ·fi 24ÒÚÔ˘. ∏ Ó¢ÚÔÏÔÁÈ΋ ÂͤٷÛË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋. ∞fi Ù· ˘fiÏÔÈ· Û˘ÛÙ‹Ì·Ù· ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∞¶ = 102/63 mmHg,
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·57
57
π‰ÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË Î·È ·¯˘Û·ÚΛ·
¶›Ó·Î·˜ 1. ¢È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÁÈ· ÙËÓ È‰ÈÔ·ı‹ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË (4) 1. ™˘ÌÙÒÌ·Ù· ‹/Î·È ÛËÌ›· ·˘ÍË̤Ó˘ ÂÓ‰ÔÎÚ¿ÓÈ·˜ ›ÂÛ˘, Ì ԛ‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ Û ·ÛıÂÓ‹ ÌÂ Ê˘ÛÈÔÏÔÁÈÎfi Â›Â‰Ô Û˘Ó›‰ËÛ˘ 2. º˘ÛÈÔÏÔÁÈ΋ Ó¢ÚÔÏÔÁÈ΋ ÂͤٷÛË, ÂÎÙfi˜ ·fi „¢‰Ò˜ ÂÛÙȷο Â˘Ú‹Ì·Ù·, fiˆ˜ ¿ÚÂÛË ÙÔ˘ ··ÁˆÁÔ‡ ‹ ÙÔ˘ ÚÔÛˆÈÎÔ‡ Ó‡ÚÔ˘ 3. ∞˘ÍË̤ÓË ÂÓ‰ÔÎÚ¿ÓÈ· ›ÂÛË (>250 mm H2O), Ì ÔÛÊ˘ÔÓˆÙÈ·›· ·Ú·Î¤ÓÙËÛË Û ϿÁÈ· ηٷÎÂÎÏÈ̤ÓË ı¤ÛË Ì ¤ÎÙ·ÛË ÙˆÓ Î¿Ùˆ ¿ÎÚˆÓ 4. º˘ÛÈÔÏÔÁÈ΋˜ Û‡ÛÙ·Û˘ ∂¡À 5. º˘ÛÈÔÏÔÁÈ΋ ·ÂÈÎfiÓÈÛË ÂÁÎÂÊ¿ÏÔ˘ ÛÙȘ Ó¢ÚÔ·ÂÈÎÔÓÈÛÙÈΤ˜ ÌÂıfi‰Ô˘˜ (·Ô˘Û›· ÂÓ‰ÔÎÚ¿ÓÈ·˜ Ì¿˙·˜, ˘‰ÚÔÎÂÊ¿ÏÔ˘, ÂÁÎÂÊ·ÏÈ΋˜ ÊÏ‚È΋˜ ıÚfiÌ‚ˆÛ˘) 6. ∫·Ì›· ¿ÏÏË ·ÈÙ›· ·˘ÍË̤Ó˘ ÂÓ‰ÔÎÚ¿ÓÈ·˜ ›ÂÛ˘
ÛÊ›ÍÂȘ = 80/min, ıÂÚÌÔÎÚ·Û›· = 36,6ÔC. ∆· ۈ̷ÙÔÌÂÙÚÈο ÛÙÔȯ›· ‹Ù·Ó: µ™ = 76 kg (90‹-97Ë ∂£), À™ = 161 cm (50‹-75Ë ∂£), BMI = 29,3 (90‹-97Ë ∂£). ¶ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ = 89 cm (90‹ ∂£) (12). ™Ù¿‰ÈÔ Tanner ÁÂÓÓËÙÈο fiÚÁ·Ó· Î·È ÂÊ‹‚·ÈÔ πππ. ∞fi ÙËÓ ÔÊı·ÏÌÔÏÔÁÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠ‰Èψ›· ÛÙËÓ ÚˆÙÂ‡Ô˘Û· ‚ÏÂÌÌ·ÙÈ΋ ı¤ÛË Î·È ·Ú·Ï˘ÙÈÎfi˜ ÛÙÚ·‚ÈÛÌfi˜, ÏfiÁˆ ¿ÚÂÛ˘ ÙÔ˘ ··ÁˆÁÔ‡ Ó‡ÚÔ˘ ·ÚÈÛÙÂÚ¿. ∏ ÔÙÈ΋ Ô͇ÙËÙ·, Ù· ÚfiÛıÈ· ÌfiÚÈ·, Ô ÎÂÚ·ÙÔÂȉ‹˜ Î·È Ù· ·ÓÙ·Ó·ÎÏ·ÛÙÈο Ù˘ ÎfiÚ˘ ‹Ù·Ó ηٿ ʇÛË. H ‚˘ıÔÛÎfiËÛË ¤‰ÂÈÍ ԛ‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ ¿Ìʈ. ∂Ï‹ÊıË Ï‹Ú˘ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Î·È ¤ÁÈÓ MRI ÂÁÎÂÊ¿ÏÔ˘, Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. ∏ √¡¶ ¤‰ÂÈÍÂ: ›ÂÛË ∂¡À 280 mm H2O, ÏÂ˘Î¿ = 5/mmÑ, ۿί·ÚÔ = 65 mg/dl Î·È Ï‡Έ̷ = 25 mg/dl. O ·ÛıÂÓ‹˜ ÂÙ¤ıË Û ıÂڷ›· Ì ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Ì ‰fiÛË 500 mg/24h. ªÂÙ¿ ÙËÓ √¡¶ ·ÚÔ˘Û›·Û ‚ÂÏÙ›ˆÛË Ù˘ ‰Èψ›·˜. ∂Í‹Ïı ÌÂÙ¿ ·fi 7 Ë̤Ú˜ ÓÔÛËÏ›·˜, Ì ·ÁˆÁ‹ ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Î·È ‰È·ÈÙËÙÈΤ˜ Ô‰ËÁ›Â˜. ∆Ô Ô›‰ËÌ· ÙˆÓ ÔÙÈÎÒÓ ıËÏÒÓ ˘Ô¯ÒÚËÛ 1 Ì‹Ó· ÌÂÙ¿ Î·È Ë Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ ‰È·ÎfiËÎÂ. ∆Ô ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ›¯Â ÂÏ·ÙÙˆı› ηٿ 5 kg. ŒÓ· ¯ÚfiÓÔ ÌÂÙ¿ ·Ú·Ì¤ÓÂÈ ·Û˘Ìو̷ÙÈÎfi˜ Î·È Ì ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜.
∆¤Ù·ÚÙË ÂÚ›ÙˆÛË ∞ÁfiÚÈ, ËÏÈΛ·˜ 12 ÂÙÒÓ, ÚÔÛ‹Ïı ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÏfiÁˆ ‰Èψ›·˜ ·fi 7Ë̤ÚÔ˘. ∆Ô ·È‰› ‹Ù·Ó ·‡ÚÂÙÔ Î·È Ë Ó¢ÚÔÏÔÁÈ΋ ÂͤٷÛË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋. ∞¶ = 114/80 mmHg, ÛÊ›ÍÂȘ = 75/min. ∆· ۈ̷ÙÔÌÂÙÚÈο ÛÙÔȯ›· ‹Ù·Ó Ù· ÂÍ‹˜: µ™ = 52 kg (75Ë ∂£), À™ = 142 cm (10Ë ∂£), BMI = 25,8 (90‹-97Ë ∂£). ¶ÂÚ›ÌÂÙÚÔ˜ ̤Û˘ = 85 cm (90‹ ∂£) (12). ™Ù¿‰ÈÔ Tanner ÁÂÓÓËÙÈο fiÚÁ·Ó· Î·È ÂÊ‹‚·ÈÔ πππ. To ÚÔÂÍ¿Ú¯ÔÓ Û‡Ìو̷ ‹Ù·Ó Ë ‰Èψ›·, Ë ÔÔ›· ÂÈÙÂÈÓfiÙ·Ó ÛÙËÓ ·ÚÈÛÙÂÚ‹ Ï¿ÁÈ·
‚ÏÂÌÌ·ÙÈ΋ ı¤ÛË. ∞fi ÙËÓ ÔÊı·ÏÌÔÏÔÁÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠԛ‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ. ™ÙËÓ MRI ÂÁÎÂÊ¿ÏÔ˘ ‰ÂÓ ˘‹Ú¯·Ó ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∏ √¡¶ ¤‰ÂÈÍÂ: ›ÂÛË ∂¡À 420 mm H2O, ÏÂ˘Î¿ = 0/mmÑ, ۿί·ÚÔ = 70 mg/dl Î·È Ï‡Έ̷ = 30 mg/dl. O ·ÛıÂÓ‹˜ ÂÙ¤ıË Û ıÂڷ›· Ì ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Ì ‰fiÛË 500 mg/24h. ∏ ‰Èψ›· ˘Ô¯ÒÚËÛÂ. ∆Ô ·È‰› ÂÍ‹Ïı ÌÂÙ¿ ·fi 6 Ë̤Ú˜ ÓÔÛËÏ›·˜ Ì ʷÚ̷΢ÙÈ΋ ·ÁˆÁ‹ ·ÎÂÙ·˙ÔÏ·Ì›‰Ë Î·È Î¿ÏÈÔ. ∂›Û˘, ‰fiıËÎ·Ó ‰È·ÈÙËÙÈΤ˜ Ô‰ËÁ›Â˜. TÔ Ô›‰ËÌ· ÙˆÓ ÔÙÈÎÒÓ ıËÏÒÓ ˘Ô¯ÒÚËÛ ÌÂÙ¿ 2 Ì‹Ó˜ Î·È ¤ÁÈÓ ‰È·ÎÔ‹ Ù˘ ·ÎÂÙ·˙ÔÏ·Ì›‰Ë˜. ∆Ô ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ›¯Â ÂÏ·ÙÙˆı› ηٿ 3 kg. ŒÓ· ¯ÚfiÓÔ ÌÂÙ¿ ÙËÓ ¤ÍÔ‰fi ÙÔ˘, ÙÔ ·È‰› ·Ú·Ì¤ÓÂÈ ·Û˘Ìو̷ÙÈÎfi.
™˘˙‹ÙËÛË ∏ π∂À Â›Ó·È ÌÈ· Û¯ÂÙÈο Û˘¯Ó‹ ÓfiÛÔ˜, Ì ÂÙ‹ÛÈ· ›وÛË 1-2 ÂÚÈÙÒÛÂȘ ·Ó¿ 100.000 ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi. ∏ ÓfiÛÔ˜ ÂÌÊ·Ó›˙ÂÙ·È Û fiϘ ÙȘ ËÏÈ˘, ·ÏÏ¿ Â›Ó·È Û˘¯ÓfiÙÂÚË Û ·¯‡Û·ÚΘ Á˘Ó·›Î˜ ·Ó··Ú·ÁˆÁÈ΋˜ ËÏÈΛ·˜. ∏ ηٷÓÔÌ‹ Â›Ó·È ·ÚfiÌÔÈ· ÛÙ· ‰‡Ô ʇϷ ÛÙËÓ ÚÔË‚È΋ ÂÚ›Ô‰Ô, ·ÏÏ¿ ÛÙËÓ ÂÊ˂›· ·Ú·ÙËÚÂ›Ù·È ¯·Ú·ÎÙËÚÈÛÙÈ΋ ˘ÂÚÔ¯‹ ÙˆÓ ·¯‡Û·ÚÎˆÓ ÎÔÚÈÙÛÈÒÓ (5). ¶ÔÏÏÔ› ·ÈÙÈÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛı› Ì π∂À (3,4). √ÚÈṲ̂ÓÔÈ ·fi ·˘ÙÔ‡˜ Â›Ó·È Î·Ï¿ ÙÂÎÌËÚȈ̤ÓÔÈ Î·È ¿ÏÏÔÈ ·Ó·Ê¤ÚÔÓÙ·È Û ÌÈÎÚ¤˜ ÛÂÈÚ¤˜ ‹ Û ÌÂÌÔӈ̤ӷ ÂÚÈÛÙ·ÙÈο. ∏ ·¯˘Û·ÚΛ· ıˆÚÂ›Ù·È ÚԉȷıÂÛÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÁÈ· π∂À, ·Ó Î·È Ô ÚfiÏÔ˜ Ù˘ ·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙÔ˜. ¶Èı·ÓfiÓ Ô‰ËÁ› Û ·˘ÍË̤ÓË ÂÓ‰ÔÎÔÈÏȷ΋ ›ÂÛË, Ë ÔÔ›· ·˘Í¿ÓÂÈ ·ÓÙ›ÛÙÔȯ· ÙËÓ ÂÓ‰ÔıˆÚ·ÎÈ΋ Î·È ÙËÓ ÂÓ‰ÔÂÁÎÂÊ·ÏÈ΋ ÊÏ‚È΋ ›ÂÛË (4). ªÂÙ·‚ÔÏÈÎÔ› Î·È ÔÚÌÔÓÈÎÔ› ·Ú¿ÁÔÓÙ˜, ÔÈ ÔÔ›ÔÈ ˘Ê›ÛÙ·ÓÙ·È ¤ÓÙÔÓ˜ ·ÏÏ·Á¤˜ Ì ÙËÓ ¤Ó·ÚÍË Ù˘ ‹‚˘ Î·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÊ˂›·˜, Èı·ÓfiÓ Ó· ¢ı‡ÓÔÓÙ·È ÁÈ· ÙË Û˘¯ÓfiÙÂÚË ÂÌÊ¿ÓÈÛË π∂À Û ·¯‡Û·ÚÎÔ˘˜ Ó·ÚÔ‡˜ ¤ÊË‚Ô˘˜ (10). ∞fi ÙÔ˘˜ Genizi J Î·È Û˘Ó. (13) ¤ÁÈÓ ÌÂÙ·Ó¿Ï˘ÛË Û 244 ÂÚÈÙÒÛÂȘ ·È‰ÈÒÓ Ì π∂À Ô˘ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ·fi ÙÔ 1996 ¤ˆ˜ ÙÔ 2006. ¢ÈÂÚ¢ӋıËÎÂ Ë Î·Ù·ÓÔÌ‹ ÙÔ˘ ʇÏÔ˘ Î·È Ë Û˘¯ÓfiÙËÙ· ·¯˘Û·ÚΛ·˜ ÌÂٷ͇ Ù˘ ÔÌ¿‰·˜ ·È‰ÈÒÓ ¤ˆ˜ 11 ÂÙÒÓ Î·È Ù˘ ÔÌ¿‰·˜ ÂÊ‹‚ˆÓ 12-17 ÂÙÒÓ. ¢È·ÈÛÙÒıËΠfiÙÈ Ë π∂À ÂÌÊ·Ó›˙ÂÙ·È ÛÙ· ·È‰È¿ ¤ˆ˜ 11 ÂÙÒÓ Ì ·ÚfiÌÔÈ· ηٷÓÔÌ‹ ʇÏÔ˘, ÂÓÒ ÛÙÔ˘˜ ÂÊ‹‚Ô˘˜ ÂÌÊ·Ó›˙ÂÙ·È Û˘¯ÓfiÙÂÚ· Û ·¯‡Û·Úη ÎÔÚ›ÙÛÈ·. ™Â 147 ·ÛıÂÓ›˜ ‰ÈÂÚ¢ӋıËÎÂ Ë ·¯˘Û·ÚΛ·. ™Â 74 ·È‰È¿ ËÏÈΛ·˜ ¤ˆ˜ 11 ÂÙÒÓ, ÌfiÓÔ 19 (26%) ‹Ù·Ó ·¯‡Û·Úη, ÂÓÒ Û 73 ÂÊ‹‚Ô˘˜ ÔÈ 47 (64%) ‹Ù·Ó ·¯‡Û·ÚÎÔÈ. ™Â ÌÂϤÙË ÙˆÓ Balcer LJ Î·È Û˘Ó. (10) Û 40 ·È‰È¿ ËÏÈΛ·˜ 3-18 ÂÙÒÓ Ì π∂À, 81% ‹Ù·Ó ·¯‡Û·Úη ÛÙȘ ËÏÈ˘ 12-14 ÂÙÒÓ Î·È 91% ÛÙȘ ËÏÈ˘ 15-17 ÂÙÒÓ. ¶·È‰È·ÙÚÈ΋ 2009;72:55-59
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·58
58
∞. ºÈÏÈ›‰Ë Î·È Û˘Ó.
™Â ÌÂϤÙË ÙˆÓ Youroukos S Î·È Û˘Ó. (14) Û 36 ·È‰È¿ Ì π∂À ËÏÈΛ·˜ 3,5 ÌËÓÒÓ ¤ˆ˜ 14 ÂÙÒÓ, ·Ó¢ڤıË Ë ·ÈÙ›· Ù˘ ÓfiÛÔ˘ Û 28 (77,7%) ·È‰È¿, Ì ‰Â‡ÙÂÚÔ ÛÂ Û˘¯ÓfiÙËÙ· ÚԉȷıÂÛÈÎfi ·Ú¿ÁÔÓÙ· ÙËÓ ·¯˘Û·ÚΛ·. ™ÙË ÌÂϤÙË ÙˆÓ Kesler A Î·È Û˘Ó. (2) Û 27 ·ÛıÂÓ›˜ ËÏÈΛ·˜ ≤16 ÂÙÒÓ Ì π∂À, 72% ‹Ù·Ó ·¯‡Û·ÚÎÔÈ fiÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ÂÊ‹‚Ô˘˜. ∞˘Ù¿ Ù· ·ÔÙÂϤÛÌ·Ù· Û˘ÌʈÓÔ‡Ó Ì ٷ ‰Â‰Ô̤ӷ Ù˘ ÚfiÛÊ·Ù˘ ·Ó¿Ï˘Û˘ fiÏˆÓ ÙˆÓ ÌÂÏÂÙÒÓ ÁÈ· π∂À Û ·È‰È¿ (13). ™Â ÌÂϤÙË ÙˆÓ Daniels A Î·È Û˘Ó. ·Ú·ÙËÚ‹ıËΠfiÙÈ ·ÎfiÌË Î·È ÌÈÎÚ‹ ·‡ÍËÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ (515%) ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· π∂À (11). ∆· Û˘Ó‹ıË Û˘ÌÙÒÌ·Ù· Ù˘ ÓfiÛÔ˘ Â›Ó·È ÎÂÊ·Ï·ÏÁ›·, Ó·˘Ù›·, ¤ÌÂÙÔÈ Î·È ÔÊı·ÏÌÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ (1-4,9). ∏ ÎÂÊ·Ï·ÏÁ›· ÂÓÙÔ›˙ÂÙ·È Û˘Ó‹ıˆ˜ ÌÂوȷ›·, ÂȉÂÈÓÒÓÂÙ·È Ì ÙËÓ Î·Ù¿ÎÏÈÛË Î·È ÌÔÚ› Ó· ·Ê˘Ó›˙ÂÈ ÙÔ ·È‰›. (9). ™Â ÈÔ ÌÈÎÚ¿ ·È‰È¿, Ù· ÚÔÂÍ¿Ú¯ÔÓÙ· Û˘ÌÙÒÌ·Ù· Â›Ó·È ˘ÓËÏ›·, ÓˆıÚfiÙËÙ· ‹ ·ÓËÛ˘¯›· (8). ∞fi ÙËÓ ÔÊı·ÏÌÔÏÔÁÈ΋ ÂͤٷÛË Û˘Ó‹ıˆ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ‰Èψ›·, ÏfiÁˆ ¿ÚÂÛ˘ Ù˘ VI ÂÁÎÂÊ·ÏÈ΋˜ Û˘˙˘Á›·˜, Î·È ‰È·Ù·Ú·¯¤˜ ÔÙÈÎÒÓ Â‰›ˆÓ (8,9). ∂›Û˘, ÌÔÚ› Ó· ·Ú·ÙËÚËı› ʈÙÔÊÔ‚›·, ÂÛˆÙÚÔ›· ηÈ, Û ·È‰È¿ ÚÈÓ ÙËÓ ‹‚Ë, ÛÙÚ·‚ÈÛÌfi˜ (9,15). ∏ ·ÒÏÂÈ· fiÚ·Û˘ ·ÔÙÂÏ› ÛÔ‚·Ú‹ ÂÈÏÔ΋ (4,9). ™˘¯Ófi ‡ÚËÌ· ·ÔÙÂÏ› ÙÔ Ô›‰ËÌ· ÙˆÓ ÔÙÈÎÒÓ ıËÏÒÓ, ÙÔ ÔÔ›Ô ÌÔÚ› Ó· Â›Ó·È ÂÙÂÚfiÏ¢ÚÔ ‹ ·ÌÊÔÙÂÚfiÏ¢ÚÔ (1,9,10). ∆Ô ‚Ú¤ÊÔ˜ ¯ˆÚ›˜ Û‡ÁÎÏÂÈÛË Ú·ÊÒÓ ÌÔÚ› Ó· ÌËÓ ·ÚÔ˘ÛÈ¿ÛÂÈ Ô›‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ, fiÙ·Ó Ë ·‡ÍËÛË Ù˘ ÂÓ‰ÔÎÚ·Óȷ΋˜ ›ÂÛ˘ Â›Ó·È ‹È· (16). ™·ÓÈfiÙÂÚ· Û˘ÌÙÒÌ·Ù· Ù˘ π∂À ·ÔÙÂÏÔ‡Ó Ë ·˘¯ÂÓ·ÏÁ›·, ÙÔ Ú·È‚fiÎÚ·ÓÔ, ÙÔ ¿ÏÁÔ˜ ˆÌÈ΋˜ ˙ÒÓ˘, ÔÈ Û·ÛÌÔ›, Ô Ó˘ÛÙ·ÁÌfi˜ Î·È Ë ·ÓˆÙÚÔ›·, ÏfiÁˆ ¿ÚÂÛ˘ IV ÂÁÎÂÊ·ÏÈ΋˜ Û˘˙˘Á›·˜ (6,7,9,13). ∏ ıÂڷ›· Ù˘ π∂À Â›Ó·È Û˘Ìو̷ÙÈ΋, Ì ÛÙfi¯Ô ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ÂÓ‰ÔÎÚ¿ÓÈ·˜ ›ÂÛ˘. ∏ ·ÎÂÙ·˙ÔÏ·Ì›‰Ë, ˆ˜ ·Ó·ÛÙÔϤ·˜ Ù˘ ηڂÔÓÈ΋˜ ·Ó˘‰Ú¿Û˘, ÂÏ·ÙÙÒÓÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ∂¡À Î·È ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÛÙË ıÂڷ›· Ù˘ ÓfiÛÔ˘ ˆ˜ Ê¿ÚÌ·ÎÔ ÚÒÙ˘ ÂÎÏÔÁ‹˜. ™Â ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ·ÎÂÙ·˙ÔÏ·Ì›‰Ë ¿Óˆ ·fi 6 Ì‹Ó˜, Â›Ó·È ··Ú·›ÙËÙÔ˜ Ô ¤ÏÂÁ¯Ô˜ ÁÈ· Èı·Ó‹ ÓÂÊÚ·Û‚¤ÛÙˆÛË. ∂¿Ó Ù· Û˘ÌÙÒÌ·Ù· ·Ú·Ì¤ÓÔ˘Ó ÌÂÙ¿ ÙË ıÂڷ›· Ì ·ÎÂÙ·˙ÔÏ·Ì›‰Ë ÁÈ· Ì›· ‚‰ÔÌ¿‰·, ÙfiÙ ÌÔÚ› Ó· Á›ÓÂÈ Â·Ó·ÏËÙÈ΋ √¡¶ (9,13,16). º·Ú̷΢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ì ÛÙÂÚÔÂȉ‹, fiˆ˜ ‰ÂÍ·ÌÂı·˙fiÓË ‹ Ú‰ÓÈ˙ÔÏfiÓË, ¤¯ÂÈ ¤Ó‰ÂÈÍË Û ÌË ·ÓÙ·fiÎÚÈÛË ‹ ‰˘Û·ÓÂÍ›· ÛÙËÓ ·ÎÂÙ·˙ÔÏ·Ì›‰Ë, ηıÒ˜ ›Û˘ Î·È Û ÛÔ‚·Úfi Ô›‰ËÌ· ÔÙÈÎÒÓ ıËÏÒÓ. ∂Ó·ÏÏ·ÎÙÈο, ÌÔÚ› Ó· ÚÔÛÙÂı› ÛÙË Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹ Ë ÊÔ˘ÚÔÛÂÌ›‰Ë (4,9,13,16). ÃÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË ¤¯ÂÈ ¤Ó‰ÂÈÍË Û ÚÔԉ¢ÙÈ΋ ‹ Ôχ ÛÔ‚·Ú‹ ÔÙÈ΋ Ó¢ÚÔ¿ıÂÈ· Î·È Û Paediatriki 2009;72:55-59
ÂÈ̤ÓÔ˘Û· ÎÂÊ·Ï·ÏÁ›· Ô˘ ÂËÚ¿˙ÂÈ ÙËÓ Î·ıËÌÂÚÈÓ‹ ‰Ú·ÛÙËÚÈfiÙËÙ·, ·Ú¿ ÙË Ê·Ú̷΢ÙÈ΋ ·ÁˆÁ‹. ¶ÂÚÈÏ·Ì‚¿ÓÂÈ ÎÔÈÏÈÔÂÚÈÙÔÓ·˚΋ ·ÚÔ¯¤Ù¢ÛË Î·È ‰ËÌÈÔ˘ÚÁ›· ·Ú·ı‡ÚÔ˘ ÛÙÔ ¤Ï˘ÙÚÔ ÙÔ˘ ÔÙÈÎÔ‡ Ó‡ÚÔ˘ (4,9,13,16). ∏ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ Â›Ó·È Î·Ï‡ÙÂÚË ÛÙ· ·È‰È¿ Û ۯ¤ÛË Ì ÙÔ˘˜ ÂÓ‹ÏÈΘ Î·È Ë ·˘ÙfiÌ·ÙË ˘Ô¯ÒÚËÛË Û˘ÓËı¤ÛÙÂÚË (1,2). √È ÁÔÓ›˜ Ú¤ÂÈ Ó· ÂÓËÌÂÚÒÓÔÓÙ·È fiÙÈ ÌÔÚ› Ó· ˘¿ÚÍÂÈ Ó¤Ô ÂÂÈÛfi‰ÈÔ π∂À Ì‹Ó˜ ‹ ¤ÙË ÌÂÙ¿ ÙÔ ÚÒÙÔ. ∞ÛıÂÓ›˜ Ì ˘ÔÙÚÔ‹ Ù˘ π∂À Ú¤ÂÈ Ó· ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È ˆ˜ Ó¤· ÂÚÈÛÙ·ÙÈο (9). ™ËÌ·ÓÙÈÎfi ‚‹Ì· ÛÙË ıÂڷ›· Ù˘ ÓfiÛÔ˘ ·ÔÙÂÏ› Ë ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Û ·¯‡Û·Úη ‹ ˘¤Ú‚·Ú· ·È‰È¿ (17). ∞ÎfiÌË Î·È ÌÈÎÚ‹ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ÌÔÚ› Ó· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ˘Ô¯ÒÚËÛË ÙÔ˘ Ôȉ‹Ì·ÙÔ˜ ÔÙÈ΋˜ ıËÏ‹˜ (9,11). ¶ÚfiÁÚ·ÌÌ· ‰›·ÈÙ·˜ Ì ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ≥2,5 kg ÂÓÙfi˜ 3 ÌËÓÒÓ ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ٷ¯‡ÙÂÚË ‚ÂÏÙ›ˆÛË ÙÔ˘ Ôȉ‹Ì·ÙÔ˜ ÔÙÈ΋˜ ıËÏ‹˜ Û ·ÛıÂÓ›˜ Ì π∂À (5). ™Â ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Ó·ÓÈ΋˜ ·¯˘Û·ÚΛ·˜, fiÔ˘ ˘¿Ú¯ÂÈ ÛÔ‚·Ú‹ ÓÔÛËÚfiÙËÙ· (۷ί·Ú҉˘ ‰È·‚‹Ù˘ Ù‡Ô˘ ππ, ·ÔÊÚ·ÎÙÈ΋ ˘ÓÈ΋ ¿ÓÔÈ·, π∂À) Î·È BMI ≥40, Û˘ÓÈÛÙ¿Ù·È ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·¯˘Û·ÚΛ·˜ (18). ∆· ·È‰È¿ Ô˘ ÌÂÏÂÙ‹ıËÎ·Ó ‹Ù·Ó ÛÙËÓ ÂÊ˂›· Î·È ‹Ù·Ó ·¯‡Û·Úη ‹ ˘¤Ú‚·Ú·. ∏ ˘ÂÚÔ¯‹ ÙˆÓ ·ÁÔÚÈÒÓ (3:1) ‰ÂÓ ·ÍÈÔÏÔÁ›ٷÈ, ÏfiÁˆ ÙÔ˘ ÌÈÎÚÔ‡ ·ÚÈıÌÔ‡. ∆Ô ·˘ÍË̤ÓÔ ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ıˆڋıËÎÂ Ô Î‡ÚÈÔ˜ ÚԉȷıÂÛÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÁÈ· ÙËÓ ÂΉ‹ÏˆÛË Ù˘ ÓfiÛÔ˘. ∏ ÛÂÙÈÚÈ˙›ÓË Ô˘ ÂÏ¿Ì‚·ÓÂ Ô ÚÒÙÔ˜ ·ÛıÂÓ‹˜ ‰ÂÓ ¤¯ÂÈ ·Ó·ÊÂÚı› ˆ˜ ·ÈÙÈÔÏÔÁÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Ù˘ π∂À. ∏ ·¯˘Û·ÚΛ· ÛÙ· ·È‰È¿ ·ÚÔ˘ÛÈ¿˙ÂÈ ÂȉËÌÈ΋ ¤Í·ÚÛË ·fi ÙÔ 1980. √ ÂÈÔÏ·ÛÌfi˜ ·˘ÍË̤ÓÔ˘ ‚¿ÚÔ˘˜ Î·È ·¯˘Û·ÚΛ·˜ Û ·È‰È¿ 5-17 ÂÙÒÓ ÛÙËÓ ∂˘ÚÒË ˘ÔÏÔÁ›˙ÂÙ·È ÛÙÔ 20% ÙË ‰ÂηÂÙ›· 1990. ŸÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÚÈÔ¯‹ Ù˘ ∫Ú‹Ù˘, Û ÌÂϤÙË ÙˆÓ ∞. ∫·Ê¿ÙÔ˘ Î·È Û˘Ó. Û ·È‰È¿ ËÏÈΛ·˜ 5-15 ÂÙÒÓ, Ô ÂÈÔÏ·ÛÌfi˜ ÙˆÓ ˘¤Ú‚·ÚˆÓ ·È‰ÈÒÓ ·˘Í‹ıËΠ·fi 21,3% Û 24,7% Î·È Ù˘ ·¯˘Û·ÚΛ·˜ ·fi 5,4% Û 10,4%, ÌÂٷ͇ ÙˆÓ ÂÚÈfi‰ˆÓ 1989-1993 Î·È 1999-2003 (19). ∞·ÈÙÂ›Ù·È Â·ÁÚ‡ÓËÛË ÙÔ˘ ·È‰È¿ÙÚÔ˘ ÁÈ· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÙˆÓ Ó·ÚÒÓ ÂÊ‹‚ˆÓ ÁÈ· ÙËÓ ÚfiÏË„Ë Ù˘ ·¯˘Û·ÚΛ·˜ Î·È ÙˆÓ ÓÔÛËÚÒÓ Î·Ù·ÛÙ¿ÛÂˆÓ Ô˘ ÙË Û˘Óԉ‡ԢÓ, ÛÙȘ Ôԛ˜ ÂÚÈÏ·Ì‚¿ÓÂÙ·È Î·È Ë È‰ÈÔ·ı‹˜ ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË.
µÈ‚ÏÈÔÁÚ·Ê›· 1. Warman R. Management of pseudotumor cerebri in children. Int Pediatr 2000;15:147-150. 2. Kesler A, Fattal-Valevski A. Idiopathic intracranial hypertension in the pediatric population. J Child Neurol 2002; 17:745-748.
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3. Haslam RHA. Pseudotumor cerebri. In: Berman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: WB Saunders; 2007. p. 2525. 4. Mercille G, Ospina LH. Pediatric idiopathic intracranial hypertension: a review. Pediatr Rev 2007; 28:77-86. 5. Skau M, Brennum J, Gjerris F, Jensen R. What is new about idiopathic intracranial hypertension? An updated review of mechanism and treatment. Cephalalgia 2006;26:384-399. 6. Speer C, Pearlman J, Phillips PH, Cooney M, Repka MX. Fourth cranial nerve palsy in pediatric patients with pseudotumor cerebri. Am J Ophthalmol 1999;127:236-237. 7. Straussberg R, Harel L, Amir J. Pseudotumor cerebri manifesting as stiff neck and torticollis. Pediatr Neurol 2002;26:225-227. 8. Lim M, Kurian M, Penn A, Calver D, Lin JP. Visual failure without headache in idiopathic intracranial hypertension. Arch Dis Child 2005;90:206-210. 9. Soler D, Cox T, Bullock P, Calver DM, Robinson RO. Diagnosis and management of benign intracranial hypertension. Arch Dis Child 1998;78:89-94. 10. Balcer LJ, Liu GT, Forman S, Pun K, Volpe NJ, Galetta SL, et al. Idiopathic intracranial hypertension: relation of age and obesity in children. Neurology 1999;52:870-872. 11. Daniels AB, Liu GT, Volpe NJ, Galetta SL, Moster ML, Newman NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol 2007;143:635-641.
12. §ÈÓ·Ú‰¿Î˘ ∂, µ·Ú‰¿‚·˜ ∞, ∫·Ê¿ÙÔ˜ ∞. ∂ηÙÔÛÙÈ·›Â˜ ı¤ÛÂȘ ÂÚÈ̤ÙÚÔ˘ ̤Û˘ ·È‰ÈÒÓ Ù˘ ∫Ú‹Ù˘ ËÏÈΛ·˜ 3 ¤ˆ˜ 16 ÂÙÒÓ. ¶·È‰È·ÙÚÈ΋ 2007;70:300-307. 13. Genizi J, Lahat E, Zelnik N, Mahajnah M, Ravid S, Shahar E. Childhood-onset idiopathic intracranial hypertension: relation of sex and obesity. Pediatr Neurol 2007;36:247-249. 14. Youroukos S, Psychou F, Fryssiras S, Paikos P, Nicolaidou P. Idiopathic intracranial hypertension in children. J Child Neurol 2000;15:453-457. 15. Cinciripini GS, Donahue S, Borchert MS. Idiopathic intracranial hypertension in prepubertal pediatric patients: characteristics, treatment, andoutcome. Am J Ophthalmol 1999;127:178-182. 16. Baker RS, Baumann RJ, Buncic JR. Idiopathic intracranial hypertension (pseudotumor cerebri) in pediatric patients. Pediatr Neurol 1989;5:5-11. 17. Stevenson SB. Pseudotumor cerebri: yet another reason to fight obesity. J Pediatr Health Care 2008;22:40-43. 18. Xanthakos SA, Inge TH. Extreme pediatric obesity: weighing the health dangers. J Pediatr 2007;150:3-5. 19. §ÈÓ·Ú‰¿Î˘ ª, ªÂÚÙÛÈ¿˜ °, ™·ÚÚ‹ ∫, ∫·Ê¿ÙÔ˜ ∞. ªÂÙ·‚ÔÏ‹ ۈ̷ÙÔÌÂÙÚÈÎÒÓ ÌÂÁÂıÒÓ, ·ÚÙËÚȷ΋˜ ›ÂÛ˘, ۷ί¿ÚÔ˘ Î·È ÏÈȉ›ˆÓ ÔÚÔ‡ ·›Ì·ÙÔ˜ ·È‰ÈÒÓ Ù˘ ∫Ú‹Ù˘ ÌÂٷ͇ ÙˆÓ ¯ÚÔÓÈÎÒÓ ÂÚÈfi‰ˆÓ 1989-1993 Î·È 19992003. ¶·È‰È·ÙÚÈ΋ 2007;70:205-216.
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CASE REPORT
™˘ÁÁÂÓ‹˜ ¯˘ÏÔıÒڷη˜ Ì ˘Ô‰fiÚÈÔ Ô›‰ËÌ· ¿Óˆ ËÌ›ÛÂÔ˜ ÛÒÌ·ÙÔ˜ Û ÓÂÔÁÓfi Ì ۇӉÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ 1 ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ ¡ÔÛËÏ›·˜ ¡ÂÔÁÓÒÓ, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ¡›Î·È·˜ «ÕÁÈÔ˜ ¶·ÓÙÂÏ‹̈ӻ 2 ∂ÚÁ·ÛÙ‹ÚÈÔ ¶·ıÔÏÔÁÈ΋˜ ∞Ó·ÙÔÌÈ΋˜, ¶·ÓÂÈÛÙ‹ÌÈÔ ∞ıËÓÒÓ AÏÏËÏÔÁÚ·Ê›·: µ·ÛÈÏÈ΋ ª·ÎÚ‹ vanessmakri@yahoo.gr À„ËÏ¿ÓÙÔ˘ 45, ¶Â‡ÎË, ∞ı‹Ó·
µ. ª·ÎÚ‹1, ∞ÈÎ. ∫ˆÓÛÙ·ÓÙÈÓ›‰Ë1, ª. ¶··‰ÔÔ‡ÏÔ˘1, Ÿ. ¢Â‰Ô‡ÛË1, ™. ∆¿ÓÙÚÔ˜1, ∂. ∞Á·ËÙfi˜2, ∞. °Ô‡Ó·Ú˘1 ¶ÂÚ›ÏË„Ë: ∏ Û˘Ó‡·ÚÍË ¯˘ÏÔıÒڷη Ì ˘Ô‰fiÚÈÔ Ô›‰ËÌ· ¿Óˆ ËÌ›ÛÂÔ˜ ÛÒÌ·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜, ÙÔ ÔÔ›Ô ÂÌÊ·Ó›˙ÂÙ·È Û˘Ó‹ıˆ˜ ›Ù ˆ˜ ÂÈÏÔ΋ ηډÈÔ¯ÂÈÚÔ˘ÚÁÈÎÒÓ ÂÂÌ‚¿ÛÂˆÓ Â›Ù ÛÙ· Ï·›ÛÈ· ÓÂÔÏ·ÛÌ·ÙÈ΋˜ ÓfiÛÔ˘ Ì ÂÈÓ¤ÌÂÛË ÛÙÔ ÌÂÛÔıˆÚ¿ÎÈÔ. π‰È·›ÙÂÚ· Û¿ÓÈ·, ÙÔ Û‡Ó‰ÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ ÌÔÚ› Ó· ÂÌÊ·ÓÈÛı› Û˘ÁÁÂÓÒ˜. ¶ÂÚÈÁÚ¿ÊÂÙ·È ÂÚ›ÙˆÛË ÚfiˆÚÔ˘ ÓÂÔÁÓÔ‡ 33 ‚‰ÔÌ¿‰ˆÓ ·ËÛ˘ Ô˘ ÁÂÓÓ‹ıËΠÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ÙÔÎÂÙfi Î·È ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË ¯ÚÂÈ¿ÛÙËΠηډÈÔ·Ó·Ó¢ÛÙÈ΋ ·Ó¿ÓË„Ë, ÂÓÒ ÛÙË Û˘Ó¤¯ÂÈ·, ÏfiÁˆ ÛËÌ·ÓÙÈ΋˜ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜, ÙÔÔıÂÙ‹ıËΠ۠Ì˯·ÓÈ΋ ˘ÔÛÙ‹ÚÈÍË Ì ˘„ËÏ‹˜ Û˘¯ÓfiÙËÙ·˜ ·ÂÚÈÛÌfi Ì ٷϷÓÙÒÛÂȘ, ÚÔÎÂÈ̤ÓÔ˘ Ó· ·ÓÙÈÌÂÙˆÈÛı› Ë ÛËÌ·ÓÙÈÎÔ‡ ‚·ıÌÔ‡ ·Ó·Ó¢ÛÙÈ΋ Î·È ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË. ∫·Ù¿ ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠÂÈÎfiÓ· Û˘Ó‰ÚfiÌÔ˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜. ™˘ÁÎÂÎÚÈ̤ӷ, ÙÔ ÓÂÔÁÓfi ÂÌÊ¿ÓÈ˙ ÂÎÛÂÛËÌ·Ṳ̂ÓÔ ˘Ô‰fiÚÈÔ Ô›‰ËÌ· ¿Óˆ ËÌ›ÛÂÔ˜ ÛÒÌ·ÙÔ˜ Î·È ·fi ÙËÓ ·ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·ÎÔ˜ ·ÔηχÊıËÎÂ Û˘ÏÏÔÁ‹ Ï¢ÚÈÙÈÎÔ‡ ˘ÁÚÔ‡ ÛÙÔ ‰ÂÍÈfi ËÌÈıˆÚ¿ÎÈÔ, Ë ·Ó¿Ï˘ÛË ÙÔ˘ ÔÔ›Ô˘ ¤‰ÂÈÍ fiÙÈ ‹Ù·Ó Û˘Ì‚·Ù‹ Ì ¯˘ÏÔıÒڷη. ¶·Ú¿ ÙËÓ ÚÔÛˆÚÈÓ‹ ‚ÂÏÙ›ˆÛË Ô˘ ·ÚÔ˘Û›·Û ÙÔ ÓÂÔÁÓfi ÌÂÙ¿ ·fi ÙËÓ ·ÚÔ¯¤Ù¢ÛË ÙÔ˘ ¯˘ÏÔıÒڷη, 12 ÒÚ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË ÂÌÊ¿ÓÈÛ ڷÁ‰·›· Âȉ›ӈÛË Ù˘ ÎÏÈÓÈ΋˜ ÂÈÎfiÓ·˜ ÏfiÁˆ Ó¢ÌÔıÒڷη ˘fi Ù¿ÛË Î·È, ·Ú¿ ÙȘ ÚÔÛ¿ıÂȘ ·Ó¿Ó˄˘, η٤ÏËÍÂ. ∏ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ ÂͤٷÛË ÙÔ˘ ÓÂÔÁÓÔ‡ ¤‰ÂÈÍ ıÚfiÌ‚ˆÛË Ù˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜.
§¤ÍÂȘ ÎÏÂȉȿ: Ã˘ÏÔıÒڷη˜, Ô›‰ËÌ·, ıÚfiÌ‚ˆÛË, ¿Óˆ ÎÔ›ÏË ÊϤ‚·.
Congenital chylothorax and subcutaneous oedema in a neonate with superior vena cava syndrome 1 NICU, “Aghios Panteleimon” General Hospital of Nikaia-Piraeus, Piraeus, Greece 2 Department of Pathology, University of Athens, Athens, Greece Correspondence: Vassiliki Makri vanessmakri@yahoo.gr 45, Ipsilantou St., Pefki, Athens, Greece
V. Makri1, A. Konstantinidi1, M. Papadopoulou1, O. Dedousi1, S. Tantros1, E. Agapitos2, A. Gounaris1 Abstract: Chylothorax and venous congestion leading to subcutaneous oedema of the upper half of the body are clinical characteristics of the superior vena cava syndrome, which usually presents either as a complication after cardiopulmonary surgery or due to local compression by underlying neoplasms of the mediastinum. In extremely rare cases, superior vena cava syndrome can occur due to congenital vascular thrombosis. This is a case report of a premature infant of 33 weeks gestation, which was delivered vaginally and needed cardiorespiratory resuscitation immediately after birth. The neonate showed signs of severe respiratory distress and arterial blood samples revealed both respiratory and metabolic acidosis, which was treated with High Frequency Oscillatory Ventilation. Physical examination revealed subcutaneous oedema of the upper half of the body, and the chest X-ray demonstrated pleural effusion of the right hemithorax, which on drainage and analysis was biochemically consistent with chylothorax. Despite temporary improvement after the chest tube drainage of the chylothorax, about 12 hours after birth the condition worsened dramatically, with the development of tension pneumothorax, which did not respond to resuscitation efforts, and the infant died. Post-mortem examination confirmed the diagnosis of superior vena cava thrombosis. Key words: Chylothorax, subcutaneous oedema, thrombosis, superior vena cava.
∂ÈÛ·ÁˆÁ‹ ø˜ ¯˘ÏÔıÒڷη˜ ÔÚ›˙ÂÙ·È Ë Ï‹ÚˆÛË Ù˘ ˘Â˙ˆÎÔÙÈ΋˜ ÎÔÈÏfiÙËÙ·˜ Ì ϤÌÊÔ ÚÔÂÚ¯fiÌÂÓË ·fi ÙÚ·‡Ì· ‹ ·fiÊÚ·ÍË ÙÔ˘ ıˆÚ·ÎÈÎÔ‡ fiÚÔ˘. √ ıˆÚ·ÎÈÎfi˜ fiÚÔ˜ ‰È·ÎÚ›ÓÂÙ·È Û Ì›˙ÔÓ· Î·È ÂÏ¿ÛÛÔÓ· Î·È Â΂¿ÏÏÂÈ ·Ú¯Èο ÛÙËÓ ·ÓÒÓ˘ÌË Î·È ÙÂÏÈο ÛÙËÓ ¿Óˆ ÎÔ›ÏË ÊϤ‚·, Ë ÔÔ›· ‰¤¯ÂÙ·È Â›Û˘ fiÏÔ ÙÔ ÊÏ‚ÈÎfi ·›Ì· ·fi Paediatriki 2009;72:60-65
ÙËÓ ÎÂÊ·Ï‹, ÙÔÓ ÙÚ¿¯ËÏÔ Î·È ·ÌÊfiÙÂÚ· Ù· ¿Óˆ ¿ÎÚ·. ø˜ ÂÎ ÙÔ‡ÙÔ˘, ÛÙÔ Û‡Ó‰ÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ (™∞∫º), Ë ·fiÊÚ·ÍË Ù˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ ÂÌÊ·Ó›˙ÂÙ·È ÎÏÈÓÈο Ì ÊÏ‚È΋ Û˘ÌÊfiÚËÛË Î·È Ô›‰ËÌ· ÎÂÊ·Ï‹˜-ÙÚ·¯‹ÏÔ˘-¿Óˆ ¿ÎÚˆÓ, ηıÒ˜ Î·È ‰ËÌÈÔ˘ÚÁ›· ¯˘ÏÔıÒڷη, ÏfiÁˆ Ù˘ ˘„ËÏ‹˜ ÊÏ‚È΋˜ ›ÂÛ˘ ÚÔ ÙÔ˘ Έχ̷ÙÔ˜, ÙÔ ÔÔ›Ô ·ÚÂÌÔ‰›˙ÂÈ ÙËÓ ÔÌ·Ï‹
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·61
61
™˘ÁÁÂÓ¤˜ Û‡Ó‰ÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜
ÏÂÌÊÈ΋ ÚÔ‹ ÂÓÙfi˜ ÙÔ˘ ıˆÚ·ÎÈÎÔ‡ fiÚÔ˘, ÚÔηÏÒÓÙ·˜ ¤ÙÛÈ ‚Ï¿‚Ë ÛÙ· Ó¢ÌÔÓÈο ÏÂÌÊ·ÁÁ›· Î·È ÂÎÚÔ‹ ϤÌÊÔ˘ ÛÙËÓ ˘Â˙ˆÎÔÙÈ΋ ÎÔÈÏfiÙËÙ·. ∂ÈϤÔÓ, Â›Ó·È ‰˘Ó·ÙfiÓ ÁÈ· ÙÔÓ ›‰ÈÔ ÏfiÁÔ Ó· ÂÌÊ·ÓÈÛı› ÂÁÎÂÊ·ÏÈ΋ ·ÈÌÔÚÚ·Á›· Î·È Ó· ÌÂȈı› ÛËÌ·ÓÙÈο Ë Î·Ú‰È·Î‹ ·ÚÔ¯‹. ™Ù· Û˘Ó‹ıË ·›ÙÈ· ÙÔ˘ ™∞∫º ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ıÚÔÌ‚ˆÙÈο Û˘Ì‚¿Ì·Ù· ÌÂÙ¿ ·fi ηډÈÔıˆÚ·ÎÈΤ˜ ÂÂÌ‚¿ÛÂȘ, Ë ÙÔÔı¤ÙËÛË ÎÂÓÙÚÈÎÒÓ ÊÏ‚ÈÎÒÓ Î·ıÂÙ‹ÚˆÓ Î·È Ë ÙÔÈ΋ ›ÂÛË Ô˘ ÌÔÚ› Ó· ·ÛÎÂ›Ù·È ÛÙËÓ ¿Óˆ ÎÔ›ÏË ÊϤ‚· ·fi ÚˆÙÔ·ı›˜ ‹ ÌÂÙ·ÛÙ·ÙÈÎÔ‡˜ fiÁÎÔ˘˜ ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ (1-4). ¶ÂÚÈÁÚ¿ÊÂÙ·È È‰È·›ÙÂÚ· Û¿ÓÈ· ÂÚ›ÙˆÛË Û˘ÁÁÂÓÔ‡˜ ™∞∫º Ô˘ ÂΉËÏÒıËΠÎÏÈÓÈο Ì ¯˘ÏÔıÒڷη Î·È ˘Ô‰fiÚÈÔ Ô›‰ËÌ· ¿Óˆ ËÌ›ÛÂÔ˜ ÛÒÌ·ÙÔ˜.
¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ÕÚÚÂÓ ÓÂÔÁÓfi, Ì ‚¿ÚÔ˜ Á¤ÓÓËÛ˘ 2.500 g, ÁÂÓÓ‹ıËΠÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ÙÔÎÂÙfi ÙËÓ 33Ë Â‚‰ÔÌ¿‰· ·ËÛ˘, ÏfiÁˆ ÚfiˆÚˆÓ Û˘Û¿ÛÂˆÓ Ù˘ ·ÏÏÔ‰·‹˜ ÌËÙ¤Ú·˜ ÙÔ˘. ™ÙË Á¤ÓÓËÛË ÙÔ ÓÂÔÁÓfi ‹Ù·Ó ΢·ÓˆÙÈÎfi, ·ÓÔ˚Îfi, Ì ηډȷÎfi Ú˘ıÌfi 70-80 ÛÊ›ÍÂȘ/ÏÂÙfi. ŒÁÈÓ ·Ú¯Èο ·Ó¿ÓË„Ë Ì ·ÛÎfi Î·È ¯ÔÚ‹ÁËÛË Ô͢ÁfiÓÔ˘, ÂÓÒ ÛÙÔ 3Ô ÏÂÙfi ‰È·ÛˆÏËÓÒıËÎÂ Î·È ·ÎÔÏÔ‡ıˆ˜ ÌÂٷʤÚıËΠÛÙÔ ÙÌ‹Ì· Ì·˜ ÁÈ· ÂÚ·ÈÙ¤Úˆ ·ÓÙÈÌÂÙÒÈÛË. ∆Ô Apgar-score ·Ó·Ê¤ÚÂÙ·È 2 ÛÙÔ 1Ô ÏÂÙfi Î·È 5 ÛÙÔ 5Ô ÏÂÙfi. ∞fi ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ·Ó·Ê¤ÚÂÙ·È fiÙÈ Î·È ÔÈ ‰‡Ô ÁÔÓ›˜ Â›Ó·È ˘ÁÈ›˜, fiˆ˜ Î·È ÙÔ 3 ÂÙÒÓ ı‹Ï˘ Ó‹ÈÔ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜. ∞fi ÙÔÓ ÚÔÁÂÓÓËÙÈÎfi ¤ÏÂÁ¯Ô, Ù· ˘ÂÚ˯ÔÁÚ·Ê‹Ì·Ù·, Ô ¤ÏÂÁ¯Ô˜ ÁÈ· Û˘ÁÁÂÓ›˜ ÏÔÈÌÒÍÂȘ Î·È Ë ·ÌÓÈԷڷΤÓÙËÛË ·Ó·Ê¤ÚÔÓÙ·È ¯ˆÚ›˜ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ· Ô˘ Ú·ÁÌ·ÙÔÔÈ‹ıËΠ۠ÙÚÈÙÔ‚¿ıÌÈÔ ÓÔÛÔÎÔÌÂ›Ô Ù˘ ∞ı‹Ó·˜, fiÔ˘ ÌÂٷʤÚıËÎÂ Ë ÌËÙ¤Ú· ÏfiÁˆ ÚfiˆÚˆÓ Û˘Û¿ÛˆÓ, ·Ó¤ÊÂÚ ÙËÓ ‡·ÚÍË ÔÏ˘˘‰Ú·ÌÓ›Ô˘ Ì Èı·Ófi ˘‰ÚÔıÒڷη, ÏËÚÔÊÔÚ›· Ô˘ ‰ÂÓ ¤ÁÈÓ ÁÓˆÛÙ‹ Û ÂÌ¿˜ ÂÁη›Úˆ˜. ∞fi ÙÔ Ì·È¢ÙÈÎfi ÈÛÙÔÚÈÎfi ·Ó·Ê¤ÚÂÙ·È Â›Û˘ fiÙÈ ÏfiÁˆ ·Ófi‰Ô˘ Ù˘ CRP, 18 ÒÚ˜ ÚÔ ÙÔ˘ ÙÔÎÂÙÔ‡, Ë ÌËÙ¤Ú· ÂÙ¤ıË Û ÂÓ‰ÔÊϤ‚È· ·ÁˆÁ‹ Ì ·ÌÈÎÈÏÏ›ÓË-ÛÔ˘ÏÌ·ÎÙ¿ÌË Î·È ¤Ï·‚ 1 ‰fiÛË ‚ËÙ·ÌÂı·˙fiÓ˘. ∫·Ù¿ ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠfiÙÈ ÚfiÎÂÈÙ·È ÁÈ· ÔȉËÌ·Ù҉˜ ÓÂÔÁÓfi, Ô˘ ¿ÊËÓ ÂÓÙ‡ˆÌ· ÛÙËÓ ›ÂÛË ÛÙËÓ ÎÂÊ·Ï‹, ÛÙÔÓ ÙÚ¿¯ËÏÔ, ÛÙ· ¿Óˆ ¿ÎÚ· Î·È ÛÙÔ ¿Óˆ ‹ÌÈÛ˘ ÙÔ˘ ıÒڷη, ÂÓÒ ÙÔ Î¿Ùˆ ‹ÌÈÛ˘ ÙÔ˘ ÛÒÌ·ÙÔ˜ ‹Ù·Ó ÂÏ¿¯ÈÛÙ· ÔȉËÌ·Ù҉˜. ¶·Ú·ÙËÚ‹ıËÎ·Ó Â›Û˘ ÌÂÁ¿ÏË ‰˘ÛÌÔÚÊ›· ÙˆÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ÙÔ˘ ÚÔÛÒÔ˘ ÏfiÁˆ ÙÔ˘ ÂÎÛÂÛËÌ·Ṳ̂ÓÔ˘ Ôȉ‹Ì·ÙÔ˜, ÌÂȈ̤ÓË Â›ÛÔ‰Ô˜ ·¤Ú· ÛÙÔ˘˜ Ó‡ÌÔÓ˜, ¢ÎÚÈÓ›˜ ηډȷÎÔ› ÙfiÓÔÈ, ¯ˆÚ›˜ ηډȷÎfi ʇÛËÌ·, „ËÏ·ÊËÙ¤˜ ÌËÚÈ-
·›Â˜ ·ÌÊÔÙÂÚfiÏ¢ڷ, „ËÏ·ÊËÙfi ‹·Ú 1,5 cm οوıÂÓ ÙÔ˘ ‰ÂÍÈÔ‡ ˘Ô¯ÔÓ‰Ú›Ô˘, ¤Íˆ ÁÂÓÓËÙÈο fiÚÁ·Ó· ¿ÚÚÂÓÔ˜. ™ÙÔ ÓÂÔÁÓfi, ÌÂÙ¿ ÙËÓ ¿ÊÈÍ‹ ÙÔ˘ ÛÙÔ ÙÌ‹Ì· Ì·˜, Û˘Ó¯›ÛÙËÎÂ Ë Î·Ú‰ÈÔ·Ó·Ó¢ÛÙÈ΋ ·Ó¿ÓË„Ë, Ô˘ ‰È‹ÚÎËÛ ÂÚ›Ô˘ 20 min. ™ÙË Û˘Ó¤¯ÂÈ·, ÙÔ ÓÂÔÁÓfi Û˘Ó‰¤ıËΠ۠·Ó·Ó¢ÛÙ‹Ú· SLE-5000 ÛÂ Û˘Á¯ÚÔÓÈṲ̂ÓÔ ‰È·Ï›ÔÓÙ· ˘Ô¯ÚˆÙÈÎfi ·ÂÚÈÛÌfi (SIMV), Ì ÛÙÔȯ›·: ̤ÁÈÛÙË ÂÈÛÓ¢ÛÙÈ΋ ›ÂÛË (PIP): 30 cm H2O, ıÂÙÈ΋ ÙÂÏÔÂÎÓ¢ÛÙÈ΋ ›ÂÛË (PEEP): 5 cm H2O, Û˘¯ÓfiÙËÙ·: 80 ·Ó·ÓÔ¤˜/ÏÂÙfi, ¯ÚfiÓÔ˜ ÂÈÛÓÔ‹˜: 0,35 sec Î·È ÎÏ¿ÛÌ· ÂÈÛÓÂfiÌÂÓÔ˘ Ô͢ÁfiÓÔ˘ (FiO2): 0,1. ∞fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô Ô˘ ‰ÈÂÓÂÚÁ‹ıËÎÂ, Ù· ·¤ÚÈ· ·ÚÙËÚÈ·ÎÔ‡ ·›Ì·ÙÔ˜ ·ÔÎ¿Ï˘„·Ó ÛËÌ·ÓÙÈÎÔ‡ ‚·ıÌÔ‡ ÌÂÈÎÙ‹ ·Ó·Ó¢ÛÙÈ΋ Î·È ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË, ÂÓÒ Ë ÁÂÓÈ΋ ·›Ì·ÙÔ˜ Î·È ÙÔ ÈÔÓÙfiÁÚ·ÌÌ· ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο (¶›Ó·Î·˜ 1). ∞ÎÔÏÔ‡ıˆ˜ ¤ÁÈÓ ·ÏÏ·Á‹ Ù˘ Ì˯·ÓÈ΋˜ ˘ÔÛÙ‹ÚÈ͢ Û ˘„ËÏ‹˜ Û˘¯ÓfiÙËÙ·˜ ·ÂÚÈÛÌfi Ì ٷϷÓÙÒÛÂȘ (HFOV), ÚÔÎÂÈ̤ÓÔ˘ Ó· ÌÂȈı› Ë ÌÂÚÈ΋ Ù¿ÛË ‰ÈÔÍÂȉ›Ô˘ ÙÔ˘ ¿Óıڷη ÛÙÔ ·›Ì· (PaCO2), ¯ˆÚ›˜ Ó· ·˘ÍËıÔ‡Ó ÂÚ·ÈÙ¤Úˆ ÔÈ Ó¢ÌÔÓÈΤ˜ ȤÛÂȘ ÚÔηÏÒÓÙ·˜ ‚·ÚfiÙÚ·˘Ì·. H ·/· ıÒÚ·ÎÔ˜ η٤‰ÂÈÍ ıÔÏÂÚfiÙËÙ· ‰ÂÍÈÔ‡ ËÌÈıˆÚ·Î›Ô˘ Û˘Ì‚·Ù‹ Ì ˘‰ÚÔıÒڷη ‰ÂÍÈ¿ Ô˘ ·ÚÂÎÙfiÈ˙ ÙËÓ Î·Ú‰È·Î‹ ÛÈÏÔ˘¤Ù· ·ÚÈÛÙÂÚ¿ (∂ÈÎfiÓ· 1). ŒÁÈÓ ·Ú·Î¤ÓÙËÛË Î·È ·ÚÔ¯ÂÙ‡ıËÎ·Ó ¿ÌÂÛ· 95 mL ÎÈÙÚÈÓˆÔ‡ ˘ÁÚÔ‡. ∏ ·Ó¿Ï˘ÛË ÙÔ˘ Ï¢ÚÈÙÈÎÔ‡ ˘ÁÚÔ‡ ¤‰ÂÈÍ fiÙÈ ÂÚfiÎÂÈÙÔ ÁÈ· ϤÌÊÔ (¶›Ó·Î·˜ 2). ™ÙË Û˘Ó¤¯ÂÈ· ÙÔÔıÂÙ‹ıËΠıˆÚ·ÎÈÎfi˜ ۈϋӷ˜ ÛÙÔ 6Ô ÌÂÛÔχÚÈÔ ‰È¿ÛÙËÌ· ‰ÂÍÈ¿, Ô˘ Û˘Ó¤¯ÈÛ ӷ ·ÚÔ¯ÂÙ‡ÂÈ Ï¤ÌÊÔ Î·È ÙÔ ÓÂÔÁÓfi ÂÙ¤ıË Û ·ÁˆÁ‹ Ì ÈÓfiÙÚÔ·, ‰ÈÔ˘ÚËÙÈο Î·È ·ÓÙÈ‚ÈÔÙÈο. ™Ù·‰È·Î¿ ˘Ô¯ÒÚËÛÂ Ë ·Ó·Ó¢ÛÙÈ΋ ÔͤˆÛË Î·È Ë ÔÍÂÔ‚·ÛÈ΋ ÈÛÔÚÚÔ›· ‚ÂÏÙÈÒıËΠÛËÌ·ÓÙÈο (¶›Ó·Î·˜ 1). ™Â ÂfiÌÂÓ˜ ·/· ıÒÚ·ÎÔ˜ ‰È·ÈÛÙÒıËΠ̛ˆÛË ÙÔ˘ ˘ÁÚÔ‡ ÛÙÔ ‰ÂÍÈfi ËÌÈıˆÚ¿ÎÈÔ, Ë Î·Ú‰È·Î‹ ÛÎÈ¿ ·ӋÏı ÛÙÔ Î¤ÓÙÚÔ ÙÔ˘ ıÒڷη, ˆÛÙfiÛÔ ·Ú¿ÏÏËÏ· ¤ÁÈÓ ÂÌÊ·Ó‹˜ ÌÈÎÚfiÙÂÚË ÔÛfiÙËÙ· ˘ÁÚÔ‡ ÛÙÔ ·ÚÈÛÙÂÚfi ËÌÈıˆÚ¿ÎÈÔ. ¶ÂÚ›Ô˘ 12 ÒÚ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË, ÙÔ ÓÂÔÁÓfi ÂÌÊ¿ÓÈÛ ڷÁ‰·›· Âȉ›ӈÛË Ù˘ ÎÏÈÓÈ΋˜ ÂÈÎfiÓ·˜, Ì ·˘Í·ÓfiÌÂÓË ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·, Ì›ˆÛË ÙÔ˘ ηٿ ÏÂÙfi ·ÂÚÈÛÌÔ‡ Î·È ÙÒÛË ÙÔ˘ ·ÚÙËÚÈ·ÎÔ‡ ÎÔÚÂÛÌÔ‡ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ Ì Ô͢ÁfiÓÔ, Ú¿ÁÌ· Ô˘ Û˘Ì‚¿‰È˙ Ì ·ÎÙÈÓÔÏÔÁÈ΋ Âȉ›ӈÛË ÙÔ˘ ˘‰ÚÔıÒڷη, Ì ·‡ÍËÛË Ù˘ ÔÛfiÙËÙ·˜ ÙÔ˘ ˘ÁÚÔ‡ ÛÙÔÓ ·ÚÈÛÙÂÚfi ˘Â˙ˆÎfiÙ·. ŒÁÈÓ ÚÔÛ¿ıÂÈ· ·Ó¿Ó˄˘ Ì ÂÎ Ó¤Ô˘ ·ÚÔ¯¤Ù¢ÛË ÙÔ˘ ¯˘ÏÔıÒڷη ·ÚÈÛÙÂÚ¿ Î·È Î·Ú‰ÈÔ·Ó·Ó¢ÛÙÈ΋ ˘ÔÛÙ‹ÚÈÍË, ¯ˆÚ›˜ fï˜ ·ÔÙ¤ÏÂÛÌ·, ÂÓÒ ·fi ÙËÓ ÙÂÏÂ˘Ù·›· ·/· ıÒÚ·ÎÔ˜ ‰È·ÈÛÙÒıËΠӢÌÔıÒڷη˜ ˘fi Ù¿ÛË ·ÚÈÛÙÂÚ¿. ¶·È‰È·ÙÚÈ΋ 2009;72:60-65
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µ. ª·ÎÚ‹ Î·È Û˘Ó.
¶›Ó·Î·˜ 1. ∂ÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜
pH pO2 pCO2 BE HCO3 §Â˘Î¿
∂Ú˘ıÚ¿ Hb Ht ¢∂∫ ∞ÈÌÔÂÙ¿ÏÈ· CRP ∆ÚÔÔÓ›ÓË I CK CK-MB √ÏÈο Ï¢ÎÒÌ·Ù· ∞Ï‚Ô˘Ì›ÓË Ca ÔÏÈÎfi Mg °Ï˘Îfi˙Ë
1Ë ÒÚ· ˙ˆ‹˜
4Ë ÒÚ· ˙ˆ‹˜
6,87 [7,35-7,50] 61 mmHg [55-80] 103 mmHg [27-40] -13 mmol/L [(-10)-(-2)] 10 mmmol/L [21-28] 18,8x109/L [9,0-30,0x109] (18,8x103/mm3) (¶: 36%, §: 53%, M: 8%, ∏: 3%) 4,08x1012/L [4,0-6,6x1012] (4,08x106/mm3) 2,48 mmol/L [2,25-3,49] (16 g/dL) 0,50 [0,48-0,69] (50%) 0,07 [0,004-0,06] (7%) 204x109/L [84-478x109] (204x103/mm3) <0,5 mg/L [<3,5] 0,18 Ìg/L [0,088-1,12] 214 U/L [214-1175] 4,7 U/L [1,7-7,9%] 33 g/L [43-76] (3,3 g/dL) 20 g/L [18-30] (2,0 g/dL) 2,22 mmol/L [2,3-2,65] (8,9 mg/dL) 1,15 mmol/L [0,48-1,05] (2,8 mg/dL) 9,8 mmol/L [1,1-3,3] (176 mg/dL)
7,50 [7,35-7,50] 191 mmHg [55-80] 20 mmHg [27-40] -7 mmol/L [(-10)-(-2)] 20,9 mmmol/L [21-28]
∂ÓÙfi˜ ·Á·Ï˘ ·Ó·ÁÚ¿ÊÔÓÙ·È ÔÈ Ê˘ÛÈÔÏÔÁÈΤ˜ ÙÈ̤˜ ÁÈ· ÙËÓ ËÏÈΛ·, Û‡Ìʈӷ Ì ÙÔ ‚È‚Ï›Ô: ¡elson Textbook of Pediatrics, 17th edition.
™ÙËÓ ÙÂÏÈ΋ ‰È·ÁÓˆÛÙÈ΋ ÚÔÛ¤ÁÁÈÛË ÙÔ˘ ÂÚÈÛÙ·ÙÈÎÔ‡ ·˘ÙÔ‡ Û˘Ó¤‚·Ï ԢÛÈ·ÛÙÈο Ë ¯·Ú·ÎÙËÚÈÛÙÈ΋ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÙÔ˘ Ôȉ‹Ì·ÙÔ˜ ·ÔÎÏÂÈÛÙÈο ÙÔ˘ ¿Óˆ ËÌ›ÛÂÔ˜ ÙÔ˘ ÛÒÌ·ÙÔ˜, Ë ÔÔ›·, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙÔÓ ¯˘ÏÔıÒڷη, ·Ú¤ÂÌ Û ۇӉÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜, οÙÈ Ô˘ ÙÂÏÈο ÂȂ‚·›ˆÛ ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋˜ ÂͤٷÛ˘, fiÔ˘ ‰È·ÈÛÙÒıËΠıÚfiÌ‚ˆÛË ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ ¶›Ó·Î·˜ 2. ∞Ó¿Ï˘ÛË Ï¢ÚÈÙÈÎÔ‡ ˘ÁÚÔ‡ §Â˘Î¿ ∂Ú˘ıÚ¿ CRP LDH °Ï˘Îfi˙Ë §Â‡ÎˆÌ· ∆ÚÈÁÏ˘ÎÂÚ›‰È· ÃÔÏËÛÙÂÚfiÏË Paediatriki 2009;72:60-65
0,48x109/L (0,48x103/mm3) (¶: 27%, §: 70%, ∏: 3%) ·ÚÎÂÙ¿ (95% ÚfiÛÊ·Ù·) 1,6 mg/L 123 IU/L 4,3 mmol/L (77 mg/dL) 24 g/L (2,4g/dL) 0,07 g/L (7 mg/dL) 0,70 mmol/L (27 mg/dL)
Î·È Ó¢ÌÔÓÈ΋ ˘ÔÏ·Û›· ÏfiÁˆ Û˘Ì›ÂÛ˘ ·fi ÙÔÓ ¯˘ÏÔıÒڷη, ηıÒ˜ Î·È ·ÏÏÔÈÒÛÂȘ Û˘Ó‰ÚfiÌÔ˘ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜.
™˘˙‹ÙËÛË √ ¯˘ÏÔıÒڷη˜ Â›Ó·È Û˘Ó‹ıˆ˜ ›ÎÙËÙÔ˜, ÌÔÓfiÏ¢ÚÔ˜ Î·È ÂÌÊ·Ó›˙ÂÙ·È Û˘¯ÓfiÙÂÚ· ·ÚÈÛÙÂÚ¿. ∆fiÛÔ ÛÙÔÓ ÂÓ‹ÏÈÎÔ fiÛÔ Î·È ÛÙÔÓ ·È‰ÈÎfi ÏËı˘ÛÌfi ÔÊ›ÏÂÙ·È Û ÔÈΛϷ ·›ÙÈ·, ÌÂ Û˘¯ÓfiÙÂÚÔ ÙËÓ ÂÈÏÔ΋ ÌÂÙ¿ ·fi ηډÈÔ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË, Ô˘ ¤¯ÂÈ ÚÔηϤÛÂÈ Ú‹ÍË ÙÔ˘ ıˆÚ·ÎÈÎÔ‡ fiÚÔ˘. ÕÏÏ· ·›ÙÈ· Â›Ó·È ÙÔ ıˆÚ·ÎÈÎfi ÙÚ·‡Ì·, Ë ÚˆÙÔ·ı‹˜ ‹ ‰Â˘ÙÂÚÔ·ı‹˜ ÂÓ‰ÔıˆÚ·ÎÈ΋ ηÎÔ‹ıÂÈ·, Ë ÏÂÌÊ·ÁÁÂȈ̿وÛË, ÔÈ ÂÚÈÔÚÈÛÙÈΤ˜ Ó¢ÌÔÓÔ¿ıÂȘ ηÈ, Ù¤ÏÔ˜, Ë Â›ÎÙËÙË ıÚfiÌ‚ˆÛË ÙÔ˘ ıˆÚ·ÎÈÎÔ‡ fiÚÔ˘, Ù˘ ˘ÔÎÏÂȉ›Ô˘ ‹ Ù˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ (™∞∫º), ÏfiÁˆ ‡·Ú͢ ÎÂÓÙÚÈÎÔ‡ ÊÏ‚ÈÎÔ‡ ηıÂÙ‹Ú· (1,4). ™ÙË ‚È‚ÏÈÔÁÚ·Ê›· ·Ó·Ê¤ÚÔÓÙ·È Û¿ÓÈ· ÂÚÈÛÙ·ÙÈο Û˘ÁÁÂÓÔ‡˜ ¯˘ÏÔıÒڷη, Ô ÔÔ›Ô˜ ÂÌÊ·Ó›˙ÂÙ·È
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™˘ÁÁÂÓ¤˜ Û‡Ó‰ÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜
∂ÈÎfiÓ· 1. ∞/· ıÒÚ·ÎÔ˜, fiÔ˘ ·ÂÈÎÔÓ›˙ÂÙ·È Û˘ÏÏÔÁ‹ ˘ÁÚÔ‡ ÛÙÔ ‰ÂÍÈfi ËÌÈıˆÚ¿ÎÈÔ (ÏÂÙ¿ ‚¤ÏË), Û˘Ì‚·Ù‹ Ì ˘‰ÚÔıÒڷη ‰ÂÍÈ¿, Ô˘ ·ÚÂÎÙÔ›˙ÂÈ ÙËÓ Î·Ú‰È·Î‹ ÛÈÏÔ˘¤Ù· ·ÚÈÛÙÂÚ¿. ¢È·ÎÚ›ÓÂÙ·È Â›Û˘ ÂÎÛÂÛËÌ·Ṳ̂ÓÔ Ô›‰ËÌ· ÎÂÊ·Ï‹˜-ÙÚ·¯‹ÏÔ˘ (¯ÔÓÙÚ¿ ‚¤ÏË).
›Ù ÌÂÌÔӈ̤ӷ [ÛÔÚ·‰ÈÎfi˜ ‹ ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ˜ Ì ·˘ÙÔÛˆÌÈÎfi ‹ Ê˘ÏÔÛ‡Ó‰ÂÙÔ ÙÚfiÔ (5)] ›Ù ÛÙ· Ï·›ÛÈ·: ·) ȉÈÔ·ıÔ‡˜ ÂÌ‚Ú˘˚ÎÔ‡ ‡‰Úˆ· ÌË ·ÓfiÛÔ˘ ·ÈÙÈÔÏÔÁ›·˜ (6,7), ‚) Û˘ÁÁÂÓÔ‡˜ Ó¢ÌÔÓÈ΋˜ ÏÂÌÊ·ÁÁÂÈÂÎÙ·Û›·˜ ›Ù ȉÈÔ·ıÔ‡˜ ›Ù ÎÏËÚÔÓÔÌÔ‡ÌÂÓ˘ (8) ›Ù ÛÙ· Ï·›ÛÈ· Û˘Ó‰ÚfiÌˆÓ Ì ÔÏϷϤ˜ Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜, fiˆ˜ Ù· Û‡Ó‰ÚÔÌ· Noonan, Turner, Down, Hennekam (9,10), Á) ÚˆÙÔ·ıÔ‡˜ ÏÂÌÊÈ΋˜ ‰˘ÛÏ·Û›·˜ (11), ‰) Û˘ÁÁÂÓÔ‡˜ ˘Ôı˘ÚÂÔÂȉÈÛÌÔ‡ (12) Î·È Â) Û˘ÁÁÂÓÔ‡˜ ·fiÊڷ͢ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ (™∞∫º) (13-15). ∞Û¯¤Ùˆ˜ Ì ÙËÓ ·ÈÙ›· ÚfiÎÏËÛ˘ ÙÔ˘ ¯˘ÏÔıÒڷη, Ë ÎÏÈÓÈ΋ ÙÔ˘ ÂÈÎfiÓ· ·Ú·Ì¤ÓÂÈ ¯·Ú·ÎÙËÚÈÛÙÈ΋, ÌÂ Û˘ÌÙÒÌ·Ù· ›ÂÛ˘ ÙfiÛÔ Â› ÙÔ˘ Ó¢ÌÔÓÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ fiÛÔ Î·È Â› Ù˘ ηډȿ˜, Ì ·ÔÙ¤ÏÂÛÌ· ÙÔ ÓÂÔÁÓfi, fiˆ˜ Î·È ÛÙËÓ ÚÔÎÂÈ̤ÓË ÂÚ›ÙˆÛË, Ó· ÂÌÊ·Ó›˙ÂÈ ‰‡ÛÓÔÈ·, ΢¿ÓˆÛË, ·Ó·Ó¢ÛÙÈ΋ Î·È Î·Ú‰È·Î‹ ·Ó¿ÚÎÂÈ·, Ì ÌÂȈ̤ÓË Î·Ú‰È·Î‹ ·ÚÔ¯‹ (1). ∏ ÔÚÈÛÙÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ ¯˘ÏÔıÒڷη Ù›ıÂÙ·È Ì ıˆÚ·ÎÔΤÓÙËÛË Î·È ·Ó¿Ï˘ÛË ÙÔ˘ Ï¢ÚÈÙÈÎÔ‡ ˘ÁÚÔ‡, ÙÔ ÔÔ›Ô Â›Ó·È Á·Ï·ÎÙ҉˜ Î·È ÂÌÂÚȤ¯ÂÈ Ï›-
Ë (ÙÚÈÁÏ˘ÎÂÚ›‰È·, ¯ÔÏËÛÙÂÚfiÏË, ¯˘ÏÔÌÈÎÚ¿), ÚˆÙ½Ó˜, ÏÂÌÊÔ·ÙÙ·Ú· Î·È ¿ÏÏ· Û˘ÛÙ·ÙÈο Ù˘ ϤÌÊÔ˘. ™Â ·˘Ùfi ÙÔ ÛËÌÂ›Ô Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÛÙ· ÓÂÔÁÓ¿ Ô˘ ‰ÂÓ ¤¯Ô˘Ó ÛÈÙÈÛı› ·ÎfiÌË, ÙÔ Ï¢ÚÈÙÈÎfi ˘ÁÚfi ÌÔÚ› Ó· Â›Ó·È ‰È·˘Á¤˜ (1,13). øÛÙfiÛÔ, ÛÙËÓ ÚÔÎÂÈ̤ÓË ÂÚ›ÙˆÛË, Ë Û˘Ó‡·ÚÍË ¯˘ÏÔıÒڷη Ì ˘Ô‰fiÚÈÔ Ô›‰ËÌ· ¿Óˆ ËÌ›ÛÂÔ˜ ÛÒÌ·ÙÔ˜ Û˘Ì‚·‰›˙ÂÈ Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÙÔ˘ ™∞∫º, οÙÈ Ô˘ ÂȂ‚·›ˆÛÂ Ë ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ ÂͤٷÛË ÙÔ˘ ÓÂÔÁÓÔ‡. ™¯ÂÙÈο Ì ٷ ·›ÙÈ· ÙÔ˘ ™∞∫º, Û˘Ó‹ıˆ˜ ÚfiÎÂÈÙ·È ÁÈ· ›ÎÙËÙË ‰È·Ù·Ú·¯‹, ·ÔÙ¤ÏÂÛÌ· ÚÔËÁËı›Û˘ ηډÈÔ¯ÂÈÚÔ˘ÚÁÈ΋˜ ¤̂·Û˘, Â͈ÙÂÚÈ΋˜ ›ÂÛ˘ ·fi ÓÂfiÏ·ÛÌ· ‹ ÙÔÔı¤ÙËÛ˘ ÎÂÓÙÚÈÎÒÓ ÊÏ‚ÈÎÒÓ Î·ıÂÙ‹ÚˆÓ (2,3). ∞fi fiÛÔ ÁÓˆÚ›˙Ô˘ÌÂ, ¤ˆ˜ ÙÒÚ· ‰ÂÓ ¤¯ÂÈ ·Ó·ÊÂÚı› ÂÚ›ÙˆÛË Û˘ÁÁÂÓÔ‡˜ ıÚfiÌ‚ˆÛ˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜, ·Ú¿ ÌfiÓÔ ¤Ó· ÂÚÈÛÙ·ÙÈÎfi Û˘ÁÁÂÓÔ‡˜ ÛÙ¤ÓˆÛ˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜ ·ÁÓÒÛÙÔ˘ ·ÈÙÈÔÏÔÁ›·˜, fiÔ˘ Ë ‰È¿ÁÓˆÛË ÂÙ¤ıË Ì ·ÁÁÂÈÔÁÚ·Ê›· Î·È Ë ·ÓˆÌ·Ï›· ·ÔηٷÛÙ¿ıËΠ̠‰È¿ÓÔÈÍË ÙÔ˘ ·ÁÁ›Ԣ Ì ̷ÏÔÓ¿ÎÈ Î·È ÙÔÔı¤ÙËÛË ÂÓ‰·ÁÁÂÈ·ÎÔ‡ stent (13), ηıÒ˜ Î·È Û¿ÓÈ· ÂÚÈÛÙ·ÙÈο Û˘ÁÁÂÓÔ‡˜ ·Ï·Û›·˜ (14) ‹ ˘ÔÏ·Û›·˜ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜, ¯ˆÚ›˜ Û˘ÓÔ‰fi Û˘ÁÁÂÓ‹ ηډȷ΋ ·ÓˆÌ·Ï›· (15). ∂ÓÒ, fï˜, ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· ‰ÂÓ ·Ó·Ê¤ÚÂÙ·È ·ÚfiÌÔÈÔ ÂÚÈÛÙ·ÙÈÎfi, ˘¿Ú¯Ô˘Ó ·Ó·ÊÔÚ¤˜ Û ۿÓȘ ÂÚÈÙÒÛÂȘ Û˘ÁÁÂÓÔ‡˜ ıÚfiÌ‚ˆÛ˘ ¿ÏÏˆÓ ·ÁÁ›ˆÓ. ™˘ÁÎÂÎÚÈ̤ӷ, ·Ó·Ê¤ÚÔÓÙ·È ÂÚÈÛÙ·ÙÈο ÂÓ‰ÔÌËÙÚ›Ô˘ ıÚfiÌ‚ˆÛ˘ Ù˘ οو ÎÔ›Ï˘ Î·È ÙˆÓ ÓÂÊÚÈÎÒÓ ÊÏ‚ÒÓ, Ô˘ ·Ô‰fiıËÎ·Ó Û ÁÂÓÂÙÈο ÎÏËÚÔÓÔÌÔ‡ÌÂÓË ıÚÔÌ‚ÔÊÈÏ›· ÙfiÛÔ Ù˘ ÌËÙ¤Ú·˜ fiÛÔ Î·È ÙÔ˘ ÂÌ‚Ú‡Ô˘, ηıÒ˜ Î·È ÛÂ Û˘Ó‰˘·ÛÌfi ·˘ÙÒÓ Ì ¤Ó· ÚÔıÚÔÌ‚ˆÙÈÎfi ÂÓ‰ÔÌ‹ÙÚÈÔ ÂÚÈ‚¿ÏÏÔÓ Ô˘ ‰ËÌÈÔ˘ÚÁ› Ë ˘¤ÚÙ·ÛË Ù˘ ÌËÙ¤Ú·˜, Ô ‰È·‚‹Ù˘ ·ËÛ˘, Ë ÚÔÂÎÏ·Ì„›· Î·È Ë ÂÓ‰ÔÌ‹ÙÚÈ· Ïԛ̈ÍË, ·ÏÏ¿ Î·È Ù· ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù· ÏfiÁˆ Ù˘ ·ÚÔ˘Û›·˜ ·˘ÙÔ·ÓÙÈۈ̿وÓ, fiˆ˜ ÙÔ ·ÓÙÈËÎÙÈÎfi ÙÔ˘ χÎÔ˘ Î·È Ù· ·ÓÙÈʈÛÊÔÏÈȉÈο ·ÓÙÈÛÒÌ·Ù· (16-19). ¶·Ú·‰Â›ÁÌ·Ù· ÎÏËÚÔÓÔÌÔ‡ÌÂÓ˘ ıÚÔÌ‚ÔÊÈÏ›·˜ (20,21), Ô˘ ÌÔÚ› Ó· ÂÌÊ·Ó›˙ÔÓÙ·È Â›Ù ÌÂÌÔӈ̤ӷ ›ÙÂ Î·È ÛÂ Û˘Ó‰˘·ÛÌfi, ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 3. ∆¤ÏÔ˜, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ·›ÙÈÔ Ô˘ ÚÔοÏÂÛ ÙË ıÚfiÌ‚ˆÛË Ù˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜, Ë ıÂڷ›· Â›Ó·È Î·Ù·Ú¯‹Ó Ë ÛÙ·ıÂÚÔÔ›ËÛË ÙÔ˘ ·ÛıÂÓÔ‡˜. ∂ÊfiÛÔÓ Ë Ï¢ÚÈÙÈ΋ Û˘ÏÏÔÁ‹ ϤÌÊÔ˘ Â›Ó·È ÌÂÁ¿ÏË, ı· ÚÔηϤÛÂÈ ÛÔ‚·Ú‹ ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· Î·È ·ÈÌÔ‰˘Ó·ÌÈ΋ ·ÛÙ¿ıÂÈ· ÏfiÁˆ Ì›ˆÛ˘ Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜, ÔfiÙ ı· ¯ÚÂÈ·ÛÙ› ›ÁÔ˘Û· ıˆÚ·ÎÔΤÓÙËÛË, ηٿ ÚÔÙ›ÌËÛË ‹‰Ë ÛÙËÓ ·›ıÔ˘Û· ÙÔÎÂÙÔ‡, Î·È ·ÚÔ¯¤Ù¢ÛË ÙÔ˘ ˘ÁÚÔ‡ Ì ÙÔÔı¤ÙËÛË ıˆÚ·ÎÈÎÔ‡ ۈϋӷ (13). ™ÙË Û˘Ó¤¯ÂÈ·, ı· Ú¤ÂÈ Ó· ÙÂÎÌËÚȈı› ·ÂÈÎÔÓÈÛÙÈο Ë ıÚfiÌ‚ˆÛË ÙÔ˘ ·ÁÁ›Ԣ ›Ù Ì ˘ÂÚ˯ÔÁÚ¿ÊËÌ· (Doppler) ›Ù Ì ·ÁÁÂÈÔÁÚ·Ê›· ¶·È‰È·ÙÚÈ΋ 2009;72:60-65
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µ. ª·ÎÚ‹ Î·È Û˘Ó.
¶›Ó·Î·˜ 3. ∞ÈÙÈÔÏÔÁ›· ÎÏËÚÔÓÔÌÔ‡ÌÂÓ˘ ıÚÔÌ‚ÔÊÈÏ›·˜ ÛÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô 1. ∞Ó¿ÚÎÂÈ· ÙˆÓ ÚˆÙÂ˚ÓÒÓ C Î·È S, Ë ÔÔ›·, ÂÓÒ Û˘Ó‹ıˆ˜ ·ÊÔÚ¿ ÌfiÓÔ Ì›· ·fi ÙȘ ‰‡Ô ·˘Ù¤˜ ÚˆÙ½Ó˜ Î·È Â›Ó·È ÂÙÂÚfi˙˘ÁÔ˜, Û·ÓÈfiÙÂÚ· ÌÔÚ› Ó· ·ÊÔÚ¿ Î·È ÙȘ ‰‡Ô (‰ÈÏ‹ ÂÙÂÚfi˙˘ÁÔ˜) ‹ Ó· Â›Ó·È ÔÌfi˙˘ÁÔ˜, ÔfiÙ Úԉȷı¤ÙÂÈ Û ÊÏ‚ÈΤ˜ ıÚÔÌ‚ÒÛÂȘ Ô˘ ÌÔÚ› Ó· ÂΉËψıÔ‡Ó ÓˆÚ›˜ ÛÙË ˙ˆ‹, ·ÎfiÌË Î·È ÂÓ‰ÔÌËÙÚ›ˆ˜ 2. ∞Ó¿ÚÎÂÈ· ·ÓÙÈıÚÔÌ‚›Ó˘-πππ 3. ÀÔ- ‹ ‰˘ÛÏ·ÛÌÈÓÔÁÔÓ·ÈÌ›· 4. ∞ÓÙ›ÛÙ·ÛË ÛÙËÓ ÂÓÂÚÁÔÔÈË̤ÓË ÚˆÙ½ÓË-C (·Ú¿ÁˆÓ-V-Leiden) 5. ∞Ó¿ÚÎÂÈ· ÙÔ˘ Û˘Ì·Ú¿ÁÔÓÙ·-ππ Ù˘ Ë·Ú›Ó˘ 6. ∞‡ÍËÛË ÂȤ‰ˆÓ ÚÔıÚÔÌ‚›Ó˘ ÛÙÔ Ï¿ÛÌ· (ÌÂÙ¿ÏÏ·ÍË ÛÙÔ ÁfiÓÔ G20210∞) 7. ∞‡ÍËÛË ÂȤ‰ˆÓ ÔÌÔ΢ÛÙ½Ó˘ ÛÙÔ Ï¿ÛÌ·, ÛÙ· Ï·›ÛÈ· ÎÏ·ÛÈ΋˜ ÔÌÔ΢ÛÙÈÓÔ˘Ú›·˜ ‹ ıÂÚÌÈ΋˜ ·ÛÙ¿ıÂÈ·˜ ÙÔ˘ ÂÓ˙‡ÌÔ˘ MTHFR ÏfiÁˆ ÔÌfi˙˘ÁÔ˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ (677C→ T)
(„ËÊȷ΋ ‹ Ì·ÁÓËÙÈ΋). ∞fi ÂΛ Î·È ¤Ú·, ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· ÚÔÙ›ÓÂÙ·È Ë ¯ÔÚ‹ÁËÛË ·ÓÙÈËÎÙÈÎÒÓ, Ë ÂÊ·ÚÌÔÁ‹ ıÚÔÌ‚ÔÏ˘ÙÈ΋˜ ·ÁˆÁ‹˜, Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ıÚÔÌ‚ÂÎÙÔÌ‹ ÚÔÎÂÈ̤ÓÔ˘ Ó· ·ÔηٷÛÙ·ı› Ë ‚·ÙfiÙËÙ· ÙÔ˘ ·ÁÁ›Ԣ ‹ Î·È Û˘Ó‰˘·ÛÌfi˜ ÙˆÓ ·Ú·¿Óˆ ηٿ ÂÚ›ÙˆÛË, ¯ˆÚ›˜ Ó· ˘¿Ú¯ÂÈ ÔÌÔʈӛ· (18,19,22,23). ¶ÚÔÎÂÈ̤ÓÔ˘ Ó· ÌÂȈı› Ë ÏÂÌÊÈ΋ ÚÔ‹ ÂÓÙfi˜ ÙÔ˘ ıˆÚ·ÎÈÎÔ‡ fiÚÔ˘ Î·È ˆ˜ ÂÎ ÙÔ‡ÙÔ˘ Ë ÂÎÚÔ‹ ϤÌÊÔ˘ ·fi Ù· ÙÚ·˘Ì·ÙÈṲ̂ӷ Ó¢ÌÔÓÈο ÏÂÌÊ·ÁÁ›· ÛÙËÓ ˘Â˙ˆÎÔÙÈ΋ ÎÔÈÏfiÙËÙ·, ÚÔÙ›ÓÂÙ·È Ë ÂÊ·ÚÌÔÁ‹ ‰›·ÈÙ·˜ ÏÔ‡ÛÈ·˜ Û ÙÚÈÁÏ˘ÎÂÚ›‰È· ̤Û˘ ·Ï‡ÛÔ˘ (MCT) Ô˘ ·ÔÚÚÔÊÒÓÙ·È ·Â˘ı›·˜ ̤ۈ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ (13). ¶ÂÚÈÁÚ¿ÊÂÙ·È È‰È·›ÙÂÚ· Û¿ÓÈÔ ÂÚÈÛÙ·ÙÈÎfi Û˘ÁÁÂÓÔ‡˜ ıÚfiÌ‚ˆÛ˘ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜, Ô˘ ¤ÁÈÓ ÎÏÈÓÈο ¤Î‰ËÏË Ì ÂÌÊ¿ÓÈÛË ˘Ô‰fiÚÈÔ˘ Ôȉ‹Ì·ÙÔ˜ ¿Óˆ ËÌ›ÛÂÔ˜ ÛÒÌ·ÙÔ˜, ηıÒ˜ Î·È Ì ¤ÓÙÔÓË ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ÔÊÂÈÏfiÌÂÓË ÛÙËÓ ‡·ÚÍË ÂÓ‰ÔÌ‹ÙÚÈÔ˘ ¯˘ÏÔıÒڷη, Ô ÔÔ›Ô˜ Ô‰‹ÁËÛ Û ˘ÔÏ·Û›· ÙÔ˘ Ó¢ÌÔÓÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜. ø˜ Èı·Ó‹ ·ÈÙ›· ÌÂÏÂÙ¿Ù·È Ë ‡·ÚÍË ÁÂÓÂÙÈο ÎÏËÚÔÓÔÌÔ‡ÌÂÓ˘ ıÚÔÌ‚ÔÊÈÏ›·˜, ›Ûˆ˜ ÛÂ Û˘Ó‰˘·ÛÌfi ÌÂ Û˘Óı‹Î˜ ÂÓ‰ÔÌËÙÚ›Ô˘ ÚÔıÚÔÌ‚ˆÙÈÎÔ‡ ÂÚÈ‚¿ÏÏÔÓÙÔ˜, Ì ÌfiÓÔ ÛÙÔÈ¯Â›Ô ·fi ÙÔ ÈÛÙÔÚÈÎfi ÙËÓ Èı·Ó‹ ‡·ÚÍË Ïԛ̈͢ Ï›Á˜ Ë̤Ú˜ ÚÔ ÙÔ˘ ÙÔÎÂÙÔ‡. √È ÁÔÓ›˜ ‰ÂÓ ‰¤¯ıËÎ·Ó Ó· Á›ÓÂÈ ¤ÏÂÁ¯Ô˜ ıÚÔÌ‚ÔÊÈÏ›·˜ ÛÙÔ˘˜ ›‰ÈÔ˘˜, ÚÔÎÂÈ̤ÓÔ˘ Ó· ‰Ôı› ÁÂÓÂÙÈ΋ Û˘Ì‚Ô˘Ï‹ ÁÈ· Èı·Ó¿ ÂfiÌÂÓ· ΢‹Ì·Ù·.
µÈ‚ÏÈÔÁÚ·Ê›· 1. Winnie GB. Chylothorax. In: Behrman RE, Kliegman RM, Jenson HB, editors. ¡elson Textbook of Pediatrics. 17th ed. International edition: Saunders; 2004. p. 1466. 2. Kramer SS, Taylor GA, Garfinkel DJ, Simmons MA. Lethal chylothoraces due to superior vena cava thrombosis in infants. Am J Roentgenol 1981;137:559-563. Paediatriki 2009;72:60-65
3. Dittrich S, Schlensak C, Kececioglu D. Successful thrombectomy of the superior vena cava thrombosis in a newborn after cardiopulmonary bypass surgery. Interact Cardiovasc Thorac Surg 2003;2:692-693. 4. Warren WH, Altman SAG. Chylothorax secondary to obstruction of the superior vena cava: a complication of the LeVeen shunt. Thorax 1990; 45:978-979. 5. King PA, Ghosh A, Tang MH, Lam SK. Recurrent congenital chylothorax. Prenat Diagn 1991;11:809-811. 6. Coulter DM. Hydrops fetalis. In: Spitzer AR, editor. Intensive care of the fetus and neonate. 2nd ed. Philadelphia: Elsevier Mosby; 2005. p. 149-157. 7. Kolben M, Zimmermann A, Schneider KT. Acute nonimmunologic hydrops fetalis with bilateral chylothorax in the 36th week of pregnancy. Geburtshilfe Frauenheilkd. 1992;52:698-701. 8. Stevenson DA, Pysher TJ, Ward RM, Carey JC. Familial congenital non-immune hydrops, chylothorax, and pulmonary lymphangiectasia. Am J Med Genet A 2006; 140:368-372. 9. Moerman P, Vandenberghe K, Devlieger H, Van Hole C, Fryns JP, Lauweryns JM. Congenital pulmonary lymphangiectasis with chylothorax: a heterogeneous lymphatic vessel abnormality. Am J Med Genet 1993;47: 54-58. 10. Bellini C, Mazzella M, Arioni C, Campisi C, Taddei G, Toma P, et al. Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia. Am J Med Genet A 2003;120:92-96. 11. Hanssler L, Metz KA, Roll C, Hennecke KH. Primary lymphatic dysplasia in a newborn infant. Montsschr Kinderheilkd 1990;138:772-774. 12. Kessel I, Makhoul IR, Suvoj P. Congenital hypothyroidism and nonimmune hydrops fetalis: associated? Pediatrics 1999;103:E9. 13. Ro PS, Hill SL, Cheatham JP. Congenital superior vena cava obstruction causing anasarca and respiratory failure in a newborn: successful transcatheter therapy. Catheter Cardiovasc Interv 2005;65:60-65. 14. Römer S, Opgen-Rhein B, Chaoui R, Scheer I, Czernik C, Obladen M. Bilateral agenesis of the superior vena cava associated with congenital hydrothorax. Ultrasound Obstet Gynecol 2006;28:842-844. 15. Lee CY, Jan SL, Wang TM, Chi CS. Congenital chylothorax associated with isolated congenital hypoplastic superior caval vein: a case report. Acta Paediatr 2005;94:1840-1843. 16. Smorgick N, Herman A, Wiener Y, Halperin R, Sherman D. Prenatal thrombosis of the inferior vena cava and the renal veins. Prenat Diagn 2007;27:603-607. 17. Boffa MC, Lachassinne E. Infant perinatal thrombosis and antiphospholipid antibodies: a review. Lupus 2007;16: 634-641. 18. Khan JU, Takemoto CM, Casella JF, Streiff MB, Nwankwo IJ, Kim HS. Catheter-directed thrombolysis of inferior vena cava thrombosis in a 13-day-old nenate and review of literature. Cardiovasc Intervent Radiol 2008;31:153-160. 19. Messinger Y, Watterson Sheaffer J, Mrozek J, Smith CM, Sinaiko AR. Renal outcome of neonatal renal venous thrombosis: review of 28 patients and effectiveness of fibrinolytics and heparin in 10 patients. Pediatrics 2006; 118:1478-1484.
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™˘ÁÁÂÓ¤˜ Û‡Ó‰ÚÔÌÔ ¿Óˆ ÎÔ›Ï˘ ÊϤ‚·˜
20. Formstone CJ, Hallam PJ, Tuddenham EGD, Voke J, Layton M, Nicolaides K, et al. Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation. Blood 1996;87:3731-3737. 21. Florell SR, Rodgers GM. Inherited thrombotic disorders: an update. Am J Hematol 1997;54:53-60. 22. Pfluger T, Czekalla R, Hundt C, Schubert M, Graubner U,
Leinsinger G, et al. MR angiography versus color Doppler sonography in the evaluation of renal vessels and the inferior vena cava in abdominal masses of pediatric patients. AJR Am J Roentgenol 1999;173:103-108. 23. Kobayashi T, Kobayashi T, Mayuzumi H, Morikawa A. Percutaneous hydrodynamic thrombectomy for congenital deep vein thrombosis in a neonate. Pediatr Cardiol 2006;27:170-174.
¶·È‰È·ÙÚÈ΋ 2009;72:60-65
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∫§π¡π∫√ ∫√Àπ∑
¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∞ÏÂÍ·Ó‰ÚÔ‡ÔÏ˘, ∞ÏÂÍ·Ó‰ÚÔ‡ÔÏË
∂. ª·ÓÙ·‰¿Î˘, Õ. ∆Û·ÏΛ‰Ë˜, Õ. ƒ·Ì·Ù¿ÓË, ∂. ¶·Ú·Ûο΢, ∞. ÷Ù˙ËÌȯ·‹Ï
AÏÏËÏÔÁÚ·Ê›·: ∂ÏȉÔÊfiÚÔ˜ ª·ÓÙ·‰¿Î˘ emantada@med.duth.gr ¢ËÌÔÎÚ›ÙÂÈÔ ¶·ÓÂÈÛÙ‹ÌÈÔ £Ú¿Î˘, ∞ÏÂÍ·Ó‰ÚÔ‡ÔÏË
Department of Paediatrics, University Hospital of Alexandroupolis, Alexandroupolis, Greece Correspondence: Elpidoforos Mantadakis emantada@med.duth.gr Democritus University of Thrace, Alexandroupolis, Greece
CLINICAL QUIZ
E. Mantadakis, A. Tsalkidis, A. Ramatani, E. Paraskakis, A. Chatzimichael ∞ÁfiÚÈ ËÏÈΛ·˜ 38 ËÌÂÚÒÓ ÚÔÛÎÔÌ›˙ÂÙ·È ÌÈ· ‰ÚÔÛÂÚ‹ ηÏÔηÈÚÈÓ‹ Ë̤ڷ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÏfiÁˆ ÚÔ˘ÎÂÙÔÂȉÒÓ ÂÌÂÙÒÓ ·fi 15Ë̤ÚÔ˘ Î·È ÌË ÚfiÛÏ˄˘ ‚¿ÚÔ˘˜. ∆Ô ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi Â›Ó·È ÂχıÂÚÔ, ÂÓÒ ÙÔ ‚Ú¤ÊÔ˜ Â›Ó·È ÙÔ ‰Â‡ÙÂÚÔ ·È‰› Ê·ÈÓÔÙ˘Èο ˘ÁÈÒÓ ÁÔÓ¤ˆÓ, ·Ï‚·ÓÈ΋˜ ηٷÁˆÁ‹˜. ∏ ÙÚ›¯ÚÔÓË ·‰ÂÏÊ‹ ÙÔ˘ Â›Ó·È ˘ÁÈ‹˜. √È ÂÌÂÙÔ› ÍÂΛÓËÛ·Ó ÂÓÒ ÙÔ ‚Ú¤ÊÔ˜ ÛÈÙÈ˙fiÙ·Ó ·ÔÎÏÂÈÛÙÈο Ì ÌËÙÚÈÎfi Á¿Ï·, ·ÏÏ¿ Û˘Ó¯›ÛÙËÎ·Ó Î·È ÌÂÙ¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÂÍ·ÓıÚˆÈṲ̂ÓÔ˘ Á¿Ï·ÙÔ˜ ˆ˜ Û˘ÌÏËÚÒÌ·ÙÔ˜ ÛÙË ‰È·ÙÚÔÊ‹. √È ÎÂÓÒÛÂȘ ÙÔ˘ ‚Ú¤ÊÔ˘˜ ÂÚÈÁÚ¿ÊÔÓÙ·È ˆ˜ Ê˘ÛÈÔÏÔÁÈΤ˜. ™ÙËÓ ÂÈÛ·ÁˆÁ‹, ÙÔ ‚Ú¤ÊÔ˜ ˙˘Á›˙ÂÈ 2.750 g, fiÛÔ Î·È ÛÙË Á¤ÓÓËÛË, Ô˘ ¤ÁÈÓ ÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ÙÔÎÂÙfi ÌÂÙ¿ ·fi ·ËÛË ‰È¿ÚÎÂÈ·˜ 40 ‚‰ÔÌ¿‰ˆÓ. ∫·Ù¿ ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË, ÙÔ ·È‰› Â›Ó·È ÛÔ‚·Ú¿ ·ÈÛ¯Ó·Ṳ̂ÓÔ, Ì ÌÂȈ̤ÓË ·Ú·ÁˆÁ‹ Ô‡ÚˆÓ Î·È ‰·ÎÚ‡ˆÓ, ·‰‡Ó·ÌÔ ÎÏ¿Ì·, ÌÂȈ̤ÓË Û·ÚÁ‹ ‰¤ÚÌ·ÙÔ˜ Î·È ÂÈÛ¤¯Ô˘Û· ÚfiÛıÈ· ËÁ‹. ∏ ·ÚÙËÚȷ΋ ›ÂÛË Â›Ó·È 85/50 mmHg, ÔÈ ÛÊ›ÍÂȘ 170/min Î·È Ë ıÂÚÌÔÎÚ·Û›· ÛÒÌ·ÙÔ˜ Ê˘ÛÈÔÏÔÁÈ΋. ∏ ÏÔÈ‹ ÂͤٷÛË ·Ó·‰ÂÈÎÓ‡ÂÈ Ì·ÚÌ·ÚÔÂȉ¤˜ ‰¤ÚÌ· ¯ˆÚ›˜ ÂÍ·Óı‹Ì·Ù·, ÂÓÒ Ë ÂͤٷÛË Ù˘ ηډȿ˜ Î·È ÙˆÓ Ó¢ÌfiÓˆÓ Â›Ó·È ¯ˆÚ›˜ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∏ ÎÔÈÏÈ¿ Â›Ó·È Â˘›ÂÛÙË, ¯ˆÚ›˜ Ë·ÙÔ-
ÛÏËÓÔÌÂÁ·Ï›·, Ì ηÏÔ‡˜ ÂÓÙÂÚÈÎÔ‡˜ ‹¯Ô˘˜. ∆· Ì·ÏÏÈ¿ Î·È Ù· Ó‡¯È· Â›Ó·È Ê˘ÛÈÔÏÔÁÈο. ∆· ÁÂÓÓËÙÈο fiÚÁ·Ó· Â›Ó·È Ê˘ÛÈÔÏÔÁÈο ¿ÚÚÂÓÔ˜ Î·È ÔÈ fiÚ¯ÂȘ Â›Ó·È ÛÙÔ fiÛ¯ÂÔ. §fiÁˆ Ù˘ ·Ê˘‰¿ÙˆÛ˘, Ô˘ ÎÏÈÓÈο ÂÎÙÈÌ‹ıËΠ۠10%, ÂÓ˘‰·ÙÒıËΠÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ÔÚfi, ÂÓ ·Ó·ÌÔÓ‹ ÙÔ˘ ·Ú¯ÈÎÔ‡ ÂÚÁ·ÛÙËÚÈ·ÎÔ‡ ÂϤÁ¯Ô˘, Ô˘ ¤‰ÂÈÍ ÏÂ˘Î¿ 10.160/mm3 Ì ÏÂÌÊÔ΢ÙÙ·ÚÈÎfi Ù‡Ô, ·ÈÌÔÛÊ·ÈÚ›ÓË 17,1 g/dl, ·ÈÌ·ÙÔÎÚ›ÙË 45%, ·ÈÌÔÂÙ¿ÏÈ· 567.000/mm3, CRP 0,1 mg/dl, ÁÏ˘Îfi˙Ë 69 mg/dl, Ô˘Ú›· 27 mg/dl, ÎÚ·ÙÈÓ›ÓË 0,5 mg/dl, Ó¿ÙÚÈÔ 104 mEq/l, οÏÈÔ 5,5 mEq/l, ¯ÏÒÚÈÔ 77 mEq/l, ·Û‚¤ÛÙÈÔ 10,2 mg/dl, ÊÒÛÊÔÚÔ 6 mg/dl, Ì·ÁÓ‹ÛÈÔ 2,1 mg/dl, SGOT 65 U/l, SGPT 74 U/l, ·ÏηÏÈ΋ ʈÛÊ·Ù¿ÛË 315 U/l, Á-GT 444 U/l, LDH 435 U/l Î·È ÔÏÈ΋ ¯ÔÏÂÚ˘ıÚ›ÓË 1,2 mg/dl. ∞¤ÚÈ· ÊÏ‚ÈÎÔ‡ ·›Ì·ÙÔ˜ ¤‰ÂÈÍ·Ó pH 7,25, pCO2 38 mmHg, Ó¿ÙÚÈÔ 107 mEq/l Î·È ‰ÈÙÙ·ÓıÚ·ÎÈο 16,7 mmol/l.
¶Èı·Ó¤˜ ‰È·ÁÓÒÛÂȘ: 1. ¶˘ÏˆÚÈ΋ ÛÙ¤ÓˆÛË 2. πÓÔ΢ÛÙÈ΋ ÓfiÛÔ˜ 3. ™˘ÁÁÂÓ‹˜ ˘ÂÚÏ·Û›· ÂÈÓÂÊÚȉ›ˆÓ 4. ∞ÓȉڈÙÈ΋ ÂÎÙÔ‰ÂÚÌÈ΋ ‰˘ÛÏ·Û›· 5. ¢È·ÙÚÔÊÈÎfi ÛÊ¿ÏÌ· ÏfiÁˆ ·Ú·›ˆÛ˘ Á¿Ï·ÙÔ˜
∏ ·¿ÓÙËÛË ÛÙË ÛÂÏ›‰· 71
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™À°Ãƒ√¡∞ £∂ª∞∆∞ µπ√™∆∞∆π™∆π∫∏™
CURRENT ISSUES OF BIOSTATISTICS
67
¶ÚÔÔÙÈΤ˜ ÏËı˘ÛÌȷΤ˜ ÌÂϤÙ˜: Ë ÂÊ·ÚÌÔÁ‹ Ù˘ ÂȉËÌÈÔÏÔÁ›·˜ ÁÈ· ÙÔÓ Î·ıÔÚÈÛÌfi ÙˆÓ ·ÈÙÈÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ·È‰È·ÙÚÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ∂. ∫ÚÈÙÛ¤ÏË, ¢.∞. ∫·ÊÂÙ˙‹˜ ¶ÂÚ›ÏË„Ë: √È ÚÔÔÙÈΤ˜ ÏËı˘ÛÌȷΤ˜ ÌÂϤÙ˜ Â›Ó·È Ô Î‡ÚÈÔ˜ ÙÚfiÔ˜ ÌÂϤÙ˘ Ô˘ ÂÊ·ÚÌfi˙ÂÙ·È ÁÈ· ÙËÓ ·ÍÈÔÏfiÁËÛË ·ÈÙÈÔÏÔÁÈÎÒÓ Û˘Û¯ÂÙ›ÛÂˆÓ ·Ó¿ÌÂÛ· ÛÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Î·È ÛÙËÓ ÂΉ‹ÏˆÛË ÓÔÛËÌ¿ÙˆÓ. ¶·ÚÔ˘ÛÈ¿˙ÂÙ·È ·Ó·ÛÎfiËÛË Ù˘ ‰ÔÌ‹˜ Î·È Ù˘ ÌÂıÔ‰ÔÏÔÁ›·˜ ÙˆÓ ÚÔÔÙÈÎÒÓ ÏËı˘ÛÌÈ·ÎÒÓ ÌÂÏÂÙÒÓ, fiˆ˜ ·˘Ù¤˜ ÂÊ·ÚÌfi˙ÔÓÙ·È ÁÈ· ÙËÓ ·ÍÈÔÏfiÁËÛË ÙˆÓ ·ÈÙÈÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÙˆÓ ·È‰È·ÙÚÈÎÒÓ ÏÔÈ̈‰ÒÓ Î·È ¯ÚfiÓÈˆÓ ÓÔÛËÌ¿ÙˆÓ. ∂ÈϤÔÓ, ·Ó·Ï‡ÔÓÙ·È ÂӉ›ÍÂȘ ÁÈ· ÙËÓ ÂÊ·ÚÌÔÁ‹ ÚÔÔÙÈÎÒÓ ÏËı˘ÛÌÈ·ÎÒÓ ÌÂÏÂÙÒÓ Î·È Ù· Ù˘¯fiÓ ÂȉËÌÈÔÏÔÁÈο ÛÊ¿ÏÌ·Ù· Ù· ÔÔ›· ‰˘Ó·ÙfiÓ Ó· ÚÔ·„Ô˘Ó Î·Ù¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘˜. ∆¤ÏÔ˜, ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ú·ÎÙÈο ·Ú·‰Â›ÁÌ·Ù· ÁÈ· ÙËÓ ·ÍÈÔÏfiÁËÛË Ù˘ ·ÈÙÈÔÏÔÁÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ·Ó¿ÌÂÛ· Û ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Î·È ÛÙËÓ Â›ÙˆÛË ·È‰È·ÙÚÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ.
µ’ ¶·ÓÂÈÛÙËÌȷ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ «¶. & ∞. ∫˘ÚÈ·ÎÔ‡», ¶·ÓÂÈÛÙ‹ÌÈÔ ∞ıËÓÒÓ AÏÏËÏÔÁÚ·Ê›·: ŒÏÂÓ· ∫ÚÈÙÛ¤ÏË ecritselis@yahoo.com µ’ ¶·ÓÂÈÛÙËÌȷ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ «¶. & ∞. ∫˘ÚÈ·ÎÔ‡», ∞ı‹Ó·
§¤ÍÂȘ ÎÏÂȉȿ: ¶ÚÔÔÙÈ΋ ÌÂϤÙË, ÂȉËÌÈÔÏÔÁ›·, ۯ‰ȷÛÌfi˜ ÌÂϤÙ˘, ·È‰È·ÙÚÈο ÓÔÛ‹Ì·Ù·.
Prospective cohort studies: the application of epidemiology in order to identify the potential determinants of paediatric diseases E. Critselis, D.A. Kafetzis Abstract: Prospective cohort studies constitute a primary means for elucidating aetiological associations between potential risk factors and the clinical manifestation of infectious and chronic diseases. A review of the structure and methodological design of prospective cohort studies within the context of investigating the determinants of infectious and chronic paediatric diseases is presented. In addition, recommended indications for the implementation of prospective cohort studies are discussed. Potential systematic epidemiological biases which may be inherently introduced are addressed. Finally, practical tutorials for evaluating the association between the exposure to risk factors and the occurrence of paediatric diseases are presented.
Second Department of Paediatrics, “P. & A. Kyriakou” Children’s Hospital, University of Athens, Athens, Greece Correspondence: Elena Critselis ecritselis@yahoo.com Second Department of Paediatrics, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece
Key words: Prospective cohort study, epidemiology, study design, pediatric disease.
∂ÈÛ·ÁˆÁ‹ √ ۯ‰ȷÛÌfi˜ ÌÂϤÙ˘ ·ÔÙÂÏ› ÙÔÓ ·ÎÚÔÁˆÓÈ·›Ô Ï›ıÔ Ù˘ ¤Ú¢ӷ˜. ∏ ÔÚı‹ ÂÈÏÔÁ‹ ÙÔ˘ ηٿÏÏËÏÔ˘ ۯ‰ȷÛÌÔ‡ Ì ÛÙfi¯Ô ÙË ‰ÈÂÚ‡ÓËÛË ÂÈÛÙËÌÔÓÈÎÒÓ ˘Ôı¤ÛÂˆÓ ‰È·ÛÊ·Ï›˙ÂÈ ÙËÓ ÂÁ΢ÚfiÙËÙ· Î·È ÙËÓ ÔÈfiÙËÙ· ÌÈ·˜ ÂÚ¢ÓËÙÈ΋˜ ÚÔÛ¿ıÂÈ·˜ Î·È ÙˆÓ Â·ÎfiÏÔ˘ıˆÓ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ. °È· ÙË ‰ÈÂÚ‡ÓËÛË Ù˘ ·ÈÙÈÔÏÔÁ›·˜ Î·È ÙˆÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ·È‰È·ÙÚÈÎÒÓ ÏÔÈ̈‰ÒÓ Î·È ¯ÚfiÓÈˆÓ ÓÔÛËÌ¿ÙˆÓ, ÛÙËÓ ÂȉËÌÈÔÏÔÁ›· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Ù¤ÛÛÂÚȘ ‚·ÛÈΤ˜ ÌÔÚʤ˜ ۯ‰ȷÛÌÔ‡ ÌÂϤÙ˘: (1) Ë ÚÔÔÙÈ΋ ‹ ·Ó·‰ÚÔÌÈ΋ ÏËı˘ÛÌȷ΋ ÌÂϤÙË (prospective or retrospective cohort study), (2) Ë ÌÂϤÙË ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ (case-control study), (3) Ë Û˘Á¯ÚÔÓÈ΋ ÌÂϤÙË (cross-sectional study) Î·È (4) Ë ÎÏÈÓÈ΋ ‰ÔÎÈÌ·Û›· (randomized trial). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·Ó·ÛÎÔÔ‡ÓÙ·È Ë ‰ÔÌ‹ Î·È Ë ÌÂıÔ‰ÔÏÔÁ›· ÙˆÓ ÚÔÔÙÈÎÒÓ
ÏËı˘ÛÌÈ·ÎÒÓ ÌÂÏÂÙÒÓ, fiˆ˜ ·˘Ù¤˜ ÂÊ·ÚÌfi˙ÔÓÙ·È ÁÈ· ÙËÓ ·ÍÈÔÏfiÁËÛË ÙˆÓ ·ÈÙÈÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÙˆÓ ·È‰È·ÙÚÈÎÒÓ ÏÔÈ̈‰ÒÓ Î·È ¯ÚfiÓÈˆÓ ÓÔÛËÌ¿ÙˆÓ. ∂ÈϤÔÓ, ·Ó·Ï‡ÔÓÙ·È ÂӉ›ÍÂȘ ÁÈ· ÙËÓ ÂÊ·ÚÌÔÁ‹ ÚÔÔÙÈÎÒÓ ÏËı˘ÛÌÈ·ÎÒÓ ÌÂÏÂÙÒÓ, Ù· ÏÂÔÓÂÎÙ‹Ì·Ù· Î·È ÌÂÈÔÓÂÎÙ‹Ì·Ù· ÙÔ˘ ۯ‰ȷÛÌÔ‡ ÌÂϤÙ˘ Î·È Ù· Ù˘¯fiÓ ÂȉËÌÈÔÏÔÁÈο ÛÊ¿ÏÌ·Ù· Ù· ÔÔ›· ‰˘Ó·ÙfiÓ Ó· ÚÔ·„Ô˘Ó Î·Ù¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘˜. ∆¤ÏÔ˜, ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ú·ÎÙÈο ·Ú·‰Â›ÁÌ·Ù· ÁÈ· ÙËÓ ·ÍÈÔÏfiÁËÛË Ù˘ ·ÈÙÈÔÏÔÁÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ·Ó¿ÌÂÛ· ÛÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Î·È ÛÙËÓ Â›ÙˆÛË ·È‰È·ÙÚÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ (¶›Ó·Î·˜ 1).
™ÎÔfi˜ ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ µ·ÛÈÎfi˜ ÛÎÔfi˜ οı ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ Â›Ó·È Ë ·ÍÈÔÏfiÁËÛË Ù˘ ¶·È‰È·ÙÚÈ΋ 2009;72:67-69
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∂. ∫ÚÈÙÛ¤ÏË, ¢.∞. ∫·ÊÂÙ˙‹˜
¶›Ó·Î·˜ 1. ¶·Ú¿‰ÂÈÁÌ· ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ ªÈ· ÚÔÔÙÈ΋ ÏËı˘ÛÌȷ΋ ÌÂϤÙË ı· ÌÔÚÔ‡Û ӷ ¤¯ÂÈ ˆ˜ ÛÎÔfi ÙËÓ ·ÍÈÔÏfiÁËÛË Ù˘ ›‰Ú·Û˘ ÙÔ˘ ·ıËÙÈÎÔ‡ ηӛÛÌ·ÙÔ˜ ÛÙËÓ Â›ÙˆÛË ‚ÚÔÁ¯ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ ÛÙ· ·È‰È¿. 1. ∆Ô ÏËı˘ÛÌÈ·Îfi ‰Â›ÁÌ· Ù˘ ÌÂϤÙ˘ ı· Ú¤ÂÈ Ó· ·ÔÙÂÏÂ›Ù·È ·fi ¤Ó· Ù˘¯·›Ô ‰Â›ÁÌ· ·È‰ÈÒÓ, 4-6 ÂÙÒÓ, ¯ˆÚ›˜ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ‹/Î·È Û˘ÌÙÒÌ·Ù· ‚ÚÔÁ¯ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜, ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘. 2. ∏ ÔÌ¿‰· Ì·ÚÙ‡ÚˆÓ Ù˘ ÌÂϤÙ˘ ı· ÂÚÈÏ·Ì‚¿ÓÂÈ ·È‰È¿ Ù· ÔÔ›· ‰ÂÓ ¤¯Ô˘Ó ÂÎÙÂı› ÔÙ¤ Û ·ıËÙÈÎfi οÓÈÛÌ·. 3. ∏ ÚÒÙË ÔÌ¿‰· Û‡ÁÎÚÈÛ˘ ı· ÂÚÈÏ·Ì‚¿ÓÂÈ ·È‰È¿ Ô˘ ¤¯Ô˘Ó ÂÎÙÂı› ÌfiÓÔ ÂÚÈÛÙ·Ûȷο Û ·ıËÙÈÎfi οÓÈÛÌ·. 4. ∏ ‰Â‡ÙÂÚË ÔÌ¿‰· Û‡ÁÎÚÈÛ˘ ı· ÂÚÈÏ·Ì‚¿ÓÂÈ ·È‰È¿ Ô˘ ¤¯Ô˘Ó ÂÎÙÂı› Û˘ÛÙËÌ·ÙÈο Û ·ıËÙÈÎfi οÓÈÛÌ·. 5. √ ÂÚ¢ÓËÙ‹˜ Ú¤ÂÈ Ó· ·Ú·ÎÔÏÔ˘ı‹ÛÂÈ ‰È·¯ÚÔÓÈο ·˘Ù¤˜ ÙȘ ÙÚÂȘ ÔÌ¿‰Â˜ ̤¯ÚÈ ÙËÓ ÂÊ˂›·, ÒÛÙ ӷ ηٷÁÚ¿„ÂÈ Î·È Ó· Û˘ÁÎÚ›ÓÂÈ ÙËÓ Â›ÙˆÛË ‚ÚÔÁ¯ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ Ô˘ ¤¯Ô˘Ó ÂÎÙÂı› ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘, ˆ˜ ÚÔ˜ ÙË ÌË ÂÎÙÂıÂÈ̤ÓË Û’ ·˘ÙfiÓ ÔÌ¿‰· Ì·ÚÙ‡ÚˆÓ. 6. ∏ ·ÈÙÈÔÏÔÁÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ ¤ÎıÂÛ˘ ηٿ ÙËÓ ·È‰È΋ ËÏÈΛ· Û ·ıËÙÈÎfi οÓÈÛÌ· Î·È ÙÔ˘ ‚ÚÔÁ¯ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ ı· ‰ڷȈı› ÂÊfiÛÔÓ Ë Â›ÙˆÛË ÓfiÛÔ˘ Ô˘ ·Ú·ÙËÚÂ›Ù·È ÙfiÛÔ ÛÙËÓ ÚÒÙË fiÛÔ Î·È ÛÙË ‰Â‡ÙÂÚË ÔÌ¿‰· Û‡ÁÎÚÈÛ˘ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ·fi ·˘Ù‹Ó Ô˘ ·Ú·ÙËÚÂ›Ù·È ÛÙËÓ ÔÌ¿‰· Ì·ÚÙ‡ÚˆÓ.
·ÈÙÈÔÏÔÁÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ·Ó¿ÌÂÛ· Û ¤Ó·Ó ‹ ÂÚÈÛÛfiÙÂÚÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ (risk factors) Î·È ÙËÓ Â›ÙˆÛË Ù˘ ÓfiÛÔ˘ (incidence rate) ‹ ÙËÓ ÂͤÏÈÍ‹ Ù˘. √È ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÌÔÚ› Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÔ˘Ó ¤Ó· ¢ڇ Ê¿ÛÌ· ·Ú·Ì¤ÙÚˆÓ, fiˆ˜ ·Ú¿ÁÔÓÙ˜ ‰ËÌÔÁÚ·ÊÈÎÔ‡˜, ÎÔÈÓˆÓÈÎÔ-ÔÈÎÔÓÔÌÈÎÔ‡˜, ÂÚÈ‚·ÏÏÔÓÙÔÏÔÁÈÎÔ‡˜, ÁÂÓÂÙÈÎÔ‡˜ Î.Ï.
™¯Â‰È·ÛÌfi˜ Î·È ‰ÈÂÍ·ÁˆÁ‹ ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ °È· ÙËÓ Ú·ÎÙÈ΋ ÂÊ·ÚÌÔÁ‹ ÌÈ·˜ ÚÔÔÙÈ΋˜ ¤Ú¢ӷ˜, ÙÔ ‰Â›ÁÌ· Ù˘ ÌÂϤÙ˘ ·ÔÙÂÏÂ›Ù·È ·fi ÔÌ¿‰· ·ÙfiÌˆÓ Ô˘ ‰ÂÓ ¤¯Ô˘Ó ÂÎÙÂı› ÛÙÔÓ ÂÓ ÏfiÁˆ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ (Ì¿ÚÙ˘Ú˜, non-exposed group) Î·È Ì›· ÔÌ¿‰· ·ÙfiÌˆÓ Ô˘, ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘, ¤¯Ô˘Ó ‹‰Ë ÂÎÙÂı› ÛÙÔÓ ›‰ÈÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ (ÔÌ¿‰· Û‡ÁÎÚÈÛ˘, exposed group). ™ËÌÂÈÒÓÂÙ·È fiÙÈ, ÛÙÔÓ Û˘ÁÎÂÎÚÈ̤ÓÔ Û¯Â‰È·ÛÌfi ÌÂϤÙ˘, ÌÔÚÔ‡Ó Ó· ÂÍÂÙ¿˙ÔÓÙ·È Û˘Á¯ÚfiÓˆ˜ ‰‡Ô ‹ Î·È ÂÚÈÛÛfiÙÂÚ˜ ÔÌ¿‰Â˜ Û‡ÁÎÚÈÛ˘, fiˆ˜ ·˘Ù¤˜ ηıÔÚ›˙ÔÓÙ·È Â›Ù ·fi ÙËÓ ¤ÎıÂÛË Û ·ÓÂÍ¿ÚÙËÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, ›Ù ·fi ÙËÓ ÔÛfiÛÙˆÛË Ù˘ ¤ÎıÂÛ˘ (.¯. ¯·ÌËÏ‹ ‹ ˘„ËÏ‹ ¤ÎıÂÛË) Û ¤Ó·Ó Û˘ÁÎÂÎÚÈ̤ÓÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘. ∂›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ÙÔÓÈÛı› fiÙÈ Î·Ù¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂϤÙ˘, ÙfiÛÔ ÛÙËÓ ÔÌ¿‰· Ì·ÚÙ‡ÚˆÓ fiÛÔ Î·È ÛÙȘ ÔÌ¿‰Â˜ Û‡ÁÎÚÈÛ˘ ı· Ú¤ÂÈ Ó· ¤¯ÂÈ ·ÔÎÏÂÈÛı› Ë ·ÚÔ˘Û›· Ù˘ ÂÍÂÙ·˙fiÌÂÓ˘ ÓfiÛÔ˘ Û ˘ÔÎÏÈÓÈ΋, Ï·Óı¿ÓÔ˘Û· ‹ Paediatriki 2009;72:67-69
ÂÓÂÚÁfi ÌÔÚÊ‹. √È ÔÌ¿‰Â˜ ˘fi ÌÂϤÙË ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ‰È·¯ÚÔÓÈο ÒÛÙ ӷ ηٷÁÚ·Ê›, Û οı ÔÌ¿‰· ͯˆÚÈÛÙ¿, Ë Â›ÙˆÛË, ıÓËÛÈÌfiÙËÙ· ‹ ıÓËÙfiÙËÙ· Ù˘ ÓfiÛÔ˘.
¶·ı‹ÛÂȘ Ô˘ ÂӉ›ÎÓ˘Ù·È Ó· ÌÂÏÂÙËıÔ‡Ó ™ÙÔ Ï·›ÛÈÔ ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÌÂÏÂÙËıÔ‡Ó Ë Â›ÙˆÛË, ıÓËÛÈÌfiÙËÙ· ‹ ıÓËÙfiÙËÙ· ÙfiÛÔ ÙˆÓ ¯ÚfiÓÈˆÓ fiÛÔ Î·È ÙˆÓ ÏÔÈ̈‰ÒÓ ·ı‹ÛˆÓ. ¶·ÚfiÏ· ·˘Ù¿, ‰‡Ô Ú·ÎÙÈο ÛËÌ›· Ú¤ÂÈ Ó· ÛËÌÂȈıÔ‡Ó. ¶ÚÒÙÔÓ, Û˘ÓÈÛÙ¿Ù·È Ë ·Ó·ÌÂÓfiÌÂÓË ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ÌÂٷ͇ Ù˘ ¤ÎıÂÛ˘ ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ Î·È Ù˘ ÎÏÈÓÈ΋˜ ÂΉ‹ÏˆÛ˘ Ù˘ ÓfiÛÔ˘ Ó· Â›Ó·È Ë Û˘ÓÙÔÌfiÙÂÚË ‰˘Ó·ÙfiÓ. ¢Â‡ÙÂÚÔÓ, ÁÈ· ÏfiÁÔ˘˜ ÔÈÎÔÓÔÌ›·˜ ÎfiÛÙÔ˘˜ Ù˘ ÌÂϤÙ˘, Û˘ÓÈÛÙ¿Ù·È Ó· ÌËÓ ·ÍÈÔÏÔÁÔ‡ÓÙ·È Û¿ÓÈ· ÓÔÛ‹Ì·Ù·, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÛÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹ ı· Ú¤ÂÈ Ó· Û˘Ïϯı› Î·È Ó· ·Ú·ÎÔÏÔ˘ıËı› ÌÂÁ¿ÏÔ ÏËı˘ÛÌÈ·Îfi ‰Â›ÁÌ·, ÒÛÙ ӷ ηٷÁÚ·Ê› ·Ú΋˜ ·ÚÈıÌfi˜ ÂÚÈÙÒÛÂˆÓ ÓfiÛÔ˘. ∂›Ó·È ÛÎfiÈÌÔ Ë ·ÍÈÔÏfiÁËÛË Û·Ó›ˆÓ ÓÔÛËÌ¿ÙˆÓ Ó· Á›ÓÂÙ·È Ì ˘ÏÈÎfi ·fi ÔÏ˘ÎÂÓÙÚÈΤ˜ ÌÂϤÙ˜. ¶ÏÂÔÓÂÎÙ‹Ì·Ù· Ù˘ ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ π‰È·›ÙÂÚ· ÛËÌ·ÓÙÈÎfi Â›Ó·È fiÙÈ, Ì ÙÔÓ Û˘ÁÎÂÎÚÈ̤ÓÔ Û¯Â‰È·ÛÌfi ÌÂϤÙ˘, Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÙÂÎÌËÚȈı› Ë ·ÈÙÈÔÏÔÁÈ΋ Û˘Û¯¤ÙÈÛË ¤ÎıÂÛ˘-ÓfiÛÔ˘, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÂÍÂÙ¿˙ÔÓÙ·È Ó¤Â˜ ÂÚÈÙÒÛÂȘ ÛÙȘ Ôԛ˜ ¤¯ÂÈ ÚÔËÁËı› Ë ¤ÎıÂÛË ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘. ªÂÈÔÓÂÎÙ‹Ì·Ù· Ù˘ ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ ø˜ ÌÂÈÔÓ¤ÎÙËÌ· Ù˘ ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ ·Ó·Ê¤ÚÂÙ·È Ë Ì·ÎÚÔ¯ÚfiÓÈ· ‰È¿ÚÎÂÈ· Ù˘ ÌÂϤÙ˘, ηْ ·ÎÔÏÔ˘ı›· ÙÔ ˘„ËÏfi ÎfiÛÙÔ˜ Î·È Ë Èı·Ó‹ ·‰˘Ó·Ì›· ·Ú·ÎÔÏÔ‡ıËÛ˘ (lost to follow-up) ÙÔ˘ ÏËı˘ÛÌÈ·ÎÔ‡ ‰Â›ÁÌ·ÙÔ˜. ∂Ó·ÏÏ·ÎÙÈÎfi˜ ۯ‰ȷÛÌfi˜ ÁÈ· ÙÔÓ ÂÚÈÔÚÈÛÌfi Ù˘ ‰È¿ÚÎÂÈ·˜ Î·È ÙÔ˘ ÎfiÛÙÔ˘˜ ∂Ó·ÏÏ·ÎÙÈÎfi˜ ۯ‰ȷÛÌfi˜ Ù˘ ÚÔÔÙÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ Â›Ó·È ·˘Ùfi˜ Ù˘ ·Ó·‰ÚÔÌÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ (retrospective cohort study), ÛÙ· Ï·›ÛÈ· ÙÔ˘ ÔÔ›Ô˘ ÂÈϤÁÂÙ·È ˘ÁÈ‹˜ ÏËı˘ÛÌfi˜, Ô˘ ¤¯ÂÈ Î·ıÈÂÚˆı› ÛÙÔ ·ÚÂÏıfiÓ (historical cohort), fiˆ˜ .¯. ÌÈ· Ù¿ÍË Ì·ıËÙÒÓ ‰ËÌÔÙÈÎÔ‡ Û¯ÔÏ›Ԣ ÚÔËÁÔ‡ÌÂÓˆÓ ÂÙÒÓ. ∏ ·ÍÈÔÏfiÁËÛË Ù˘ ¤ÎıÂÛ˘ ÙˆÓ ÂÍÂÙ·˙fiÌÂÓˆÓ ÛÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Á›ÓÂÙ·È ‚¿ÛÂÈ È·ÙÚÈÎÒÓ ‹ ¿ÏÏˆÓ ·Ú¯Â›ˆÓ. ∆· ̤ÏË ÙÔ˘ ÏËı˘ÛÌÔ‡ ·Ó¢ڛÛÎÔÓÙ·È, ÛÙËÓ ·ÚÔ‡Û· ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô Î·È Û ÌÂÙ·ÁÂÓ¤ÛÙÂÚË ËÏÈΛ·, ÒÛÙÂ
Pediatric Jan-Feb 09
16-03-09
14:56
™ÂÏ›‰·69
69
¶ÚÔÔÙÈΤ˜ ÏËı˘ÛÌȷΤ˜ ÌÂϤÙ˜
Ó· ηٷÁÚ·Ê› Ë Â›ÙˆÛË ÓfiÛÔ˘. ªÂ ÙËÓ ÂÊ·ÚÌÔÁ‹ ·˘ÙÔ‡ ÙÔ˘ ۯ‰ȷÛÌÔ‡ ÌÂÈÒÓÂÙ·È ÛËÌ·ÓÙÈο Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Î·È ÙÔ ÎfiÛÙÔ˜ Ù˘ ÌÂϤÙ˘. ™ËÌ·ÓÙÈÎfi Â›Ó·È Ó· ÛËÌÂȈı› fiÙÈ, Ë ‚·ÛÈ΋ ‰ÔÌ‹ Ù˘ ·Ó·‰ÚÔÌÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘ ‰ÂÓ ‰È·Ê¤ÚÂÈ ·fi ·˘Ù‹Ó Ù˘ ÚÔÔÙÈ΋˜ ÌÂϤÙ˘. ™˘ÁÎÂÎÚÈ̤ӷ, Î·È ÛÙȘ ‰‡Ô ÌÂϤÙ˜ Û˘ÁÎÚ›ÓÔÓÙ·È Ë ÔÌ¿‰· Ô˘ ¤¯ÂÈ ÂÎÙÂı› ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÚÔ˜ ÙËÓ ÔÌ¿‰· Ô˘ ‰ÂÓ ¤¯ÂÈ ÂÎÙÂı› Û’ ·˘ÙfiÓ, ˆ˜ ÚÔ˜ ÙËÓ Â›ÙˆÛË Ù˘ ÓfiÛÔ˘. ∏ Û‡ÁÎÚÈÛË ·˘Ù‹ ·ÔÙÂÏ› Î·È ÙËÓ È‰È·›ÙÂÚË Ù·˘ÙfiÙËÙ· οı ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘.
¶Èı·Ó¿ Û˘ÛÙËÌ·ÙÈο ÛÊ¿ÏÌ·Ù· ÌÂϤÙ˘ ∫·Ù¿ ÙË ‰ÈÂÍ·ÁˆÁ‹ ÌÈ·˜ ÚÔÔÙÈ΋˜ ‹ ·Ó·‰ÚÔÌÈ΋˜ ÏËı˘ÛÌȷ΋˜ ÌÂϤÙ˘, ÂÓ‰¤¯ÂÙ·È Ó· ÚÔ·„Ô˘Ó Ù· ·ÎfiÏÔ˘ı· Û˘ÛÙËÌ·ÙÈο ÛÊ¿ÏÌ·Ù·. 1. ™Ê¿ÏÌ· ·ÍÈÔÏfiÁËÛ˘ ·ÔÙÂϤÛÌ·ÙÔ˜ (bias in the assessment of outcome) ∂Ó‰¤¯ÂÙ·È Ó· ÚÔ·„ÂÈ fiÙ·Ó Ô ÂÚ¢ÓËÙ‹˜ Ô˘ ·ÍÈÔÏÔÁ› ÙËÓ Â›ÙˆÛË ÓfiÛÔ˘ ÁÓˆÚ›˙ÂÈ ÔÈ· ¿ÙÔÌ· ¤¯Ô˘Ó ÂÎÙÂı› ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘, ÔfiÙ ÂËÚ¿˙ÂÙ·È Ë ÎÚ›ÛË ÙÔ˘. ∞˘Ùfi ÙÔ ÛÊ¿ÏÌ· ÌÔÚ› Ó· ·ÔÊ¢¯ı› ÂÊfiÛÔÓ Â›ÙÂ Ô ÂÚ¢ÓËÙ‹˜ ‰ÂÓ ÂÓËÌÂÚˆı› Û¯ÂÙÈο Ì ÙËÓ ¤ÎıÂÛË ÙˆÓ ·ÙfiÌˆÓ ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ (Ù˘ÊÏ‹ ·ÍÈÔÏfiÁËÛË, blind assessment) ›Ù ÎÏËıÔ‡Ó ‰‡Ô ‰È·ÊÔÚÂÙÈÎÔ› ÂÚ¢ÓËÙ¤˜ Ó· ·ÍÈÔÏÔÁ‹ÛÔ˘Ó ÙËÓ Â›ÙˆÛË ÓfiÛÔ˘ ·ÓÂÍ¿ÚÙËÙ·. 2. ™Ê¿ÏÌ· ÏËÚÔÊfiÚËÛ˘ (information bias) ∂Ó‰¤¯ÂÙ·È Ó· ÚÔ·„ÂÈ Û ÂÚÈÙÒÛÂȘ ÛÙȘ Ôԛ˜ Ë ¤ÎÙ·ÛË Î·È Ë ÔÈfiÙËÙ· ÙˆÓ ÏËÚÔÊÔÚÈÒÓ ·fi ÙÔ ÏËı˘ÛÌÈ·Îfi ‰Â›ÁÌ· ‰È·Ê¤ÚÂÈ ÛËÌ·ÓÙÈο, ·Ó¿ÏÔÁ· Ì ÙÔ ·Ó ÔÈ Û˘ÌÌÂÙ¤¯ÔÓÙ˜ ÛÙË ÌÂϤÙË ¤¯Ô˘Ó ÂÎÙÂı› ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘. ∆Ô ÛÊ¿ÏÌ· ÏËÚÔÊfiÚËÛ˘ Â›Ó·È ÈÔ Èı·Ófi Ó· ÚÔ·„ÂÈ Î·Ù¿ ÙË ‰ÈÂÍ·ÁˆÁ‹ ·Ó·‰ÚÔÌÈÎÒÓ ÏËı˘ÛÌÈ·ÎÒÓ ÌÂÏÂÙÒÓ. 3. ™Ê¿ÏÌ· ÏfiÁˆ ·‰˘Ó·Ì›·˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ (bias from non-responses and lost to follow-up) ∂ËÚ¿˙ÂÈ ¿ÌÂÛ· ÙËÓ ·ÍÈÔÈÛÙ›· Ù˘ ÌÂϤÙ˘, ‰Â‰Ô̤ÓÔ˘ Ù˘ ·‰˘Ó·Ì›·˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ·ÙfiÌˆÓ Ô˘ ÓÔÛÔ‡Ó, Ì ·ÎfiÏÔ˘ıÔ ÙÔÓ Ï·Óı·Ṳ̂ÓÔ ˘ÔÏÔÁÈÛÌfi Ù˘ ›وÛ˘ ÓfiÛÔ˘.
∂ȉËÌÈÔÏÔÁÈΤ˜ Î·È ‚ÈÔÛÙ·ÙÈÛÙÈΤ˜ ·Ú¿ÌÂÙÚÔÈ ∫‡ÚÈÔ˜ ÛÎÔfi˜ οı ÚÔÔÙÈ΋˜ ÌÂϤÙ˘ Â›Ó·È Ë ÛÙ·ÙÈÛÙÈ΋ ‰ڷ›ˆÛË Ù˘ ·ÈÙÈÔÏÔÁÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ·Ó¿ÌÂÛ· Û ¤Ó·Ó ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ Î·È ÙËÓ ˘fi ÌÂϤÙË ÓfiÛÔ. °È· ÙÔÓ ÛÎÔfi ·˘Ùfi, Á›ÓÔÓÙ·È ÔÈ ·ÎfiÏÔ˘ıÔÈ ˘ÔÏÔÁÈÛÌÔ›, Ì ‚¿ÛË ÙÔÓ ¶›Ó·Î· 2.
¶›Ó·Î·˜ 2. ÀÔıÂÙÈ΋ ηٷÓÔÌ‹ ÏËı˘ÛÌÔ‡ ÚÔÔÙÈ΋˜ ÌÂϤÙ˘
ŒÎıÂÛË ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ªË ¤ÎıÂÛË ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘
¶·ÚÔ˘Û›· ÓfiÛÔ˘
∞Ô˘Û›· ÓfiÛÔ˘
∂›ÙˆÛË ÓfiÛÔ˘
a
b
πÔÛ = a / (a + b)
c
d
πÔÌ = c / (c+d)
∂›ÙˆÛË ÓfiÛÔ˘ ÛÙËÓ ÔÌ¿‰· Û‡ÁÎÚÈÛ˘ (πÔÛ) ∂›Ó·È Ô ÏfiÁÔ˜ ÙˆÓ Ó¤ˆÓ ÂÚÈÙÒÛÂˆÓ ÓfiÛÔ˘ Û ¿ÙÔÌ· Ô˘ ¤¯Ô˘Ó ÂÎÙÂı› ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÚÔ˜ ÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÙfiÌˆÓ Ô˘ ¤¯Ô˘Ó ÂÎÙÂı› Û’·˘ÙfiÓ: πÔÛ = a / (a+b). ∂›ÙˆÛË ÓfiÛÔ˘ ÛÙËÓ ÔÌ¿‰· Ì·ÚÙ‡ÚˆÓ (πÔÌ) ∂›Ó·È Ô ÏfiÁÔ˜ ÙˆÓ Ó¤ˆÓ ÂÚÈÙÒÛÂˆÓ ÓfiÛÔ˘ Û ¿ÙÔÌ· Ô˘ ‰ÂÓ ¤¯Ô˘Ó ÂÎÙÂı› ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÚÔ˜ ÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÙfiÌˆÓ Ô˘ ‰ÂÓ ¤¯Ô˘Ó ÂÎÙÂı› Û’·˘ÙfiÓ: πÔÌ = c / (c+d). ™¯ÂÙÈÎfi˜ ∫›Ó‰˘ÓÔ˜ (Relative Risk, RR) ∂›Ó·È Ô ÏfiÁÔ˜ Ù˘ ›وÛ˘ ÓfiÛÔ˘ ÛÙËÓ ÔÌ¿‰· Û‡ÁÎÚÈÛ˘ (ÂÎÙÂıÂÈ̤ÓÔ˘˜) ÚÔ˜ ÙËÓ Â›ÙˆÛË ÛÙËÓ ÔÌ¿‰· Ì·ÚÙ‡ÚˆÓ (ÌË ÂÎÙÂıÂÈ̤ÓÔ˘˜): RR = πÔÛ / πÔÌ. ∂¿Ó Ë ÙÈÌ‹ ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Â›Ó·È ›ÛË Ì ÙË ÌÔÓ¿‰· (RR=1), ÙfiÙÂ Ô Î›Ó‰˘ÓÔ˜ (›وÛË) ÓfiÛÔ˘ Û ÂÎÙÂıÂÈ̤ӷ ¿ÙÔÌ· ÈÛÔ‡Ù·È Ì ÙÔÓ Î›Ó‰˘ÓÔ ÓfiÛÔ˘ Û ÌË ÂÎÙÂıÂÈ̤ӷ ¿ÙÔÌ·, ‰ËÏ·‰‹ ‰ÂÓ ˘¿Ú¯ÂÈ ¤Ó‰ÂÈÍË ·ÈÙÈÔÏÔÁÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ·Ó¿ÌÂÛ· ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ Î·È ÙËÓ Â›ÙˆÛË ÓfiÛÔ˘. ∂¿Ó Ë ÙÈÌ‹ ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ·fi ÙË ÌÔÓ¿‰· (RR>1), ÙfiÙÂ Ô Î›Ó‰˘ÓÔ˜ ÓfiÛÔ˘ Û ÂÎÙÂıÂÈ̤ӷ ¿ÙÔÌ· Â›Ó·È ÌÂÁ·Ï‡ÙÂÚÔ˜ ·fi ·˘ÙfiÓ Û ÌË ÂÎÙÂıÂÈ̤ӷ ¿ÙÔÌ·, ÔfiÙ ˘¿Ú¯ÂÈ ¤Ó‰ÂÈÍË ıÂÙÈ΋˜ ·ÈÙÈÔÏÔÁÈ΋˜ Û˘Û¯¤ÙÈÛ˘ ·Ó¿ÌÂÛ· ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ Î·È ÙËÓ Â›ÙˆÛË ÓfiÛÔ˘. ∆¤ÏÔ˜, Â¿Ó Ë ÙÈÌ‹ ÙÔ˘ Û¯ÂÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Â›Ó·È ÌÈÎÚfiÙÂÚË ·fi ÙË ÌÔÓ¿‰· (RR<1), ÙfiÙÂ Ô Î›Ó‰˘ÓÔ˜ ÓfiÛÔ˘ Û ÂÎÙÂıÂÈ̤ӷ ¿ÙÔÌ· Â›Ó·È ÌÈÎÚfiÙÂÚÔ˜ ·fi ·˘ÙfiÓ Û ÌË ÂÎÙÂıÂÈ̤ӷ ¿ÙÔÌ·, ‰ËÏ·‰‹ ˘¿Ú¯ÂÈ ·ÚÓËÙÈ΋ (ÚÔÛٷ٢ÙÈ΋) Û˘Û¯¤ÙÈÛË ·Ó¿ÌÂÛ· ÛÙÔÓ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ Î·È ÙËÓ Â›ÙˆÛË ÓfiÛÔ˘.
µÈ‚ÏÈÔÁÚ·Ê›· 1. Gordis L. 1996. Epidemiology. WB Saunders Company. Pennsylvania, USA. 2. Rothman KJ, Greenland S. 1998. Modern Epidemiology, Second Edition. Lippincott Williams & Wilkins, Pennsylvania, USA. 3. Szklo M, Nieto FJ. 2000. Epidemiology: Beyond the Basics. Aspen Publishers. Maryland, USA. ¶·È‰È·ÙÚÈ΋ 2009;72:67-69
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¡∂∞ ∞¶√ ∆√ ¢π∞¢π∫∆À√
NEWS FROM THE INTERNET
http://www.paidiatros.com ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¡ÔÛÔÎÔÌ›Ԣ §¿Úӷη˜, §¿Úӷη, ∫‡ÚÔ˜ AÏÏËÏÔÁÚ·Ê›·: ∞‰¿ÌÔ˜ ÷Ù˙Ë·Ó·Á‹˜ adamos@paidiatros.com ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¡ÔÛÔÎÔÌÂ›Ô §¿Úӷη˜ 6301, §¿Úӷη ∫‡ÚÔ˜
Pediatric Department, Larnaca General Hospital, Larnaca, Cyprus Correspondence: Adamos Hadjipanayis adamos@paidiatros.com Pediatric Department Larnaca General Hospital 6301, Larnaca Cyprus
Paediatriki 2009;72:70
∞. ÷Ù˙Ë·Ó·Á‹˜
∏ ÈÛÙÔÛÂÏ›‰· www.paidiatros.com ·Â˘ı‡ÓÂÙ·È ÛÙÔ˘˜ ÁÔÓ›˜, ·ÏÏ¿ Î·È Û ·ÁÁÂÏ̷ٛ˜ ˘Á›·˜ (·È‰›·ÙÚÔ˘˜, ÁÂÓÈÎÔ‡˜ ÁÈ·ÙÚÔ‡˜ Î.Ù.Ï.). ™ÙËÓ Î‡ÚÈ· ÛÂÏ›‰· ı· ‚Ú›Ù ÙÔ «∂›Î·ÈÚÔ ı¤Ì·», ÙÔ ÔÔ›Ô Ú·ÁÌ·Ù‡ÂÙ·È Ù· ÙÚ¤¯ÔÓÙ· ı¤Ì·Ù· Ô˘ ··Û¯ÔÏÔ‡Ó ÙÔÓ ÁÔÓÈfi. ∆Ô ı¤Ì· ·˘Ùfi, ·Ó¿ÏÔÁ· Ì ÙË ÚÔ‹ ÙˆÓ Âȉ‹ÛˆÓ, ·Ó·ÓÂÒÓÂÙ·È Î¿ı 8-12 ̤Ú˜. ™ÙÔ Î˘Ú›ˆ˜ ÌÂÓÔ‡ ·ÚÈÛÙÂÚ¿, ÌÔÚ› Ó· ‚ÚÂÈ Ô ¯Ú‹ÛÙ˘ ÙȘ ηÙËÁÔڛ˜ ÙˆÓ ıÂÌ¿ÙˆÓ. ∫¿ı ηÙËÁÔÚ›· ÂÚÈÏ·Ì‚¿ÓÂÈ ÏËıÒÚ· ¿ÚıÚˆÓ Ô˘ ·Ó·Ï‡Ô˘Ó Ì ÙÚfiÔ ÂÎÏ·˚ÎÂ˘Ì¤ÓÔ ı¤Ì·Ù· Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔ ·È‰› (·fi ÙË Û‡ÏÏË„Ë Ì¤¯ÚÈ Î·È ÙËÓ ÂÓËÏÈΛˆÛË). À¿Ú¯Ô˘Ó ›ÎÔÛÈ ÎÂÊ¿Ï·È· Ù· ÔÔ›· ÂÚȤ¯Ô˘Ó ÂÚÈÛÛfiÙÂÚ· ·fi 400 ‰È·ÊÔÚÂÙÈο ¿ÚıÚ·. ∏ Ì˯·Ó‹ ·Ó·˙‹ÙËÛ˘ οÓÂÈ ÙËÓ ·Ó‡ÚÂÛË ÙÔ˘ ¿ÚıÚÔ˘ Ô˘ „¿¯ÓÂÙ ¿Ú· Ôχ ‡ÎÔÏË. ∆·˘Ùfi¯ÚÔÓ·, fï˜, Â›Ó·È Î·Ù·¯ˆÚË̤ӷ fiÏ· Ù· ¿ÚıÚ· Û ·ÏÊ·‚ËÙÈ΋ ÛÂÈÚ¿. √ ÁÔÓÈfi˜ ¤¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ÚˆÙ‹ÛÂÈ ÙËÓ Â›ÏÂÎÙË ÔÌ¿‰· ÂȉÈÎÒÓ ÁÈ· ÔÔÈÔ‰‹ÔÙ ı¤Ì· ÙÔÓ ··Û¯ÔÏ›, Ô˘ ·ÊÔÚ¿ ÙÔ ·È‰› ÙÔ˘. ∏ ÂÚÒÙËÛË ı· ··ÓÙËı› ÙÔ Û˘ÓÙÔÌfiÙÂÚÔ ‰˘Ó·ÙfiÓ ·fi ÙÔÓ ·ÚÌfi‰ÈÔ ÁÈ· ÙÔ ı¤Ì· ÂȉÈÎfi. ™ÙÔ ·Ú¯Â›Ô È·ÙÚÒÓ ˘¿Ú¯Ô˘Ó ηٷ¯ˆÚË̤ӷ Ù· ÛÙÔȯ›· fiÏˆÓ ÙˆÓ ·È‰È¿ÙÚˆÓ Ù˘ ∫‡ÚÔ˘ Î·È Û˘Ó·ÊÒÓ ÂȉÈÎÔÙ‹ÙˆÓ (·È‰Ô„˘¯ÔÏfiÁˆÓ, ÔÚıÔ‰ÔÓÙÈÎÒÓ Î.Ù.Ï.). ∏ ÈÛÙÔÛÂÏ›‰· Û¿˜ ‰›ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ‚Ú›Ù ÙÔ Ê·ÚÌ·ÎÂ›Ô Ô˘ ÂÊËÌÂÚ‡ÂÈ Û ÔÔÈ·‰‹ÔÙ ·گ›· Ù˘ ∫‡ÚÔ˘. ∂›Û˘, ‰È·ı¤ÙÂÈ ·›ıÔ˘Û· Û˘˙‹ÙËÛ˘ ÛÙËÓ ÔÔ›· ÔÈ ÁÔÓ›˜ ·ÓÙ·ÏÏ¿ÛÛÔ˘Ó ·fi„ÂȘ ÁÈ· ÎÔÈÓ¿ ı¤Ì·Ù· Ô˘ ÙÔ˘˜ ··Û¯ÔÏÔ‡Ó. ∂›Ó·È ¤Ó·˜ ¯ÒÚÔ˜ fiÔ˘ ÔÈ ÁÔÓ›˜ ÌÔÈÚ¿˙ÔÓÙ·È Ù· ÚÔ‚Ï‹Ì·Ù· Î·È ÙȘ ·ÓËÛ˘¯›Â˜ ÙÔ˘˜. ¶·ÙÒÓÙ·˜ ÛÙÔ Û‡Ó‰ÂÛÌÔ «°È· ·È‰È¿ÙÚÔ˘˜», ı· Ô‰ËÁËı›Ù ÛÙËÓ ÎÂÓÙÚÈ΋ ÛÂÏ›‰· Ù˘ ÈÛÙÔÛÂÏ›‰·˜ ÙˆÓ Â·ÁÁÂÏÌ·ÙÈÒÓ ˘Á›·˜ (http://www.peds.paidiatros.com). °È· Ó· ÙËÓ ÂÈÛÎÂÊı›Ù ڤÂÈ Ó· ›ÛÙ ̤ÏÔ˜ - ÌÔÚ›Ù ӷ Á›ÓÂÙ ̤ÏÔ˜ ¯ˆÚ›˜ η̛· ·Ôχو˜ ÂÈ‚¿Ú˘ÓÛË. √ ¯Ú‹ÛÙ˘ Û ·˘Ù‹ ÙË ÈÛÙÔÛÂÏ›‰· ÌÔÚ› Ó· ‰È·‚¿ÛÂÈ ÂÚÈÏ‹„ÂȘ ·fi ÙËÓ ÙÚ¤¯Ô˘Û· ‚È‚ÏÈÔÁÚ·Ê›·, Ó· ‚ÚÂÈ ÙÔ Û˘Ó¤‰ÚÈÔ Ô˘ ÙÔÓ ÂӉȷʤÚÂÈ ÛÙËÓ ∫‡ÚÔ, ÛÙËÓ ∂ÏÏ¿‰·, ·ÏÏ¿ Î·È Û ÔÔÈ·‰‹ÔÙ ¯ÒÚ· ÙÔ˘ ÎfiÛÌÔ˘. ∂›Û˘, Û·˜ ‰›ÓÂÙ·È Ë ‰˘Ó·ÙfiÙËÙ· Ó· ηٷ¯ˆÚ‹ÛÂÙ ÙÔ ‰ÈÎfi Û·˜ Û˘Ó¤‰ÚÈÔ. ∂ӉȷʤÚÔÓ Â›Ó·È ÙÔ ÎÏÈÓÈÎfi Quiz ÙÔ˘ Ì‹Ó·, fiÔ˘ ÂÚÈÁÚ¿ÊÂÙ·È ¤Ó· Û¯ÂÙÈο Û¿ÓÈÔ ÂÚÈÛÙ·ÙÈÎfi Î·È ÔÈ ¯Ú‹ÛÙ˜ Ô˘ ı· ‚ÚÔ˘Ó ÙË ‰È¿ÁÓˆÛË Ì·›ÓÔ˘Ó ÛÙË ÎÏ‹ÚˆÛË ÁÈ· ÙËÓ ·fiÎÙËÛË ÂÓfi˜ ‚È‚Ï›Ô˘ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ¶·È‰È·ÙÚÈ΋. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÈÛÙÔÛÂÏ›‰· www.paidiatros.com ·ÔÙÂÏ› ÌÈ· ·ÍÈfiÈÛÙË ËÁ‹ ÏËÚÔÊfiÚËÛ˘ ÁÈ· ı¤Ì·Ù· ˘Á›·˜ ÙˆÓ ·È‰ÈÒÓ, ÙfiÛÔ ÁÈ· ÙÔ˘˜ ÁÔÓ›˜ fiÛÔ Î·È ÁÈ· ÙÔ˘˜ ·ÁÁÂÏ̷ٛ˜ ˘Á›·˜.
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∞¶∞¡∆∏™∏ ¢È¿ÁÓˆÛË: ™˘ÁÁÂÓ‹˜ ˘ÂÚÏ·Û›· ÂÈÓÂÊÚȉ›ˆÓ
∆Ô ÚÔÂͤ¯ÔÓ ·fi Ù· ÎÏÈÓÈο Â˘Ú‹Ì·Ù· ÙÔ˘ ‚Ú¤ÊÔ˘˜ ‹Ù·Ó Ë ÛÔ‚·Ú‹ ·›Û¯Ó·ÛË Î·È Ë ·Ê˘‰¿ÙˆÛË. ∞fi Ù· ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù·, ÚÔ›¯·Ó Ë ·ÂÈÏËÙÈ΋ ÁÈ· ÙË ˙ˆ‹ ˘ÔÓ·ÙÚÈ·ÈÌ›· Î·È ÏÈÁfiÙÂÚÔ Ë ˘ÂÚηÏÈ·ÈÌ›·. H ÙÂÏÂ˘Ù·›·, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË, ηıÒ˜ Î·È Ë ·ÚÓËÙÈ΋ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË Ù˘ ÎÔÈÏÈ¿˜ ÁÈ· „ËÏ·ÊËÙ‹ Ì¿˙· Ù‡Ô˘ «ÂÏ·›·˜» ÛÙÔ ÂÈÁ¿ÛÙÚÈÔ ·ÔÌ·ÎÚ‡ÓÔ˘Ó ÙËÓ Èı·ÓfiÙËÙ· ˘ÏˆÚÈ΋˜ ÛÙ¤ÓˆÛ˘, ÛÙËÓ ÔÔ›· ı· ·Ó·ÌÂÓfiÙ·Ó ˘ÔηÏÈ·ÈÌ›· Î·È ·ÏοψÛË. ∏ ÈÓÔ΢ÛÙÈ΋ ÓfiÛÔ˜ ÌÔÚ› Ó· ÂΉËψı› Ì ·›Û¯Ó·ÛË ÏfiÁˆ ‰˘Û·ÔÚÚfiÊËÛ˘ (ÔÈ ÎÂÓÒÛÂȘ ÙÔ˘ ‚Ú¤ÊÔ˘˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈΤ˜), ÌÂ Û˘ÓÔ‰fi ˘ÔÓ·ÙÚÈ·ÈÌ›· Î·È ˘Ô¯ÏˆÚÈ·ÈÌ›· ÏfiÁˆ ·ÒÏÂÈ·˜ ¿Ï·ÙÔ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ôχ ˙ÂÛÙÒÓ ËÌÂÚÒÓ, Û˘Ó‹ıˆ˜ fï˜ Û ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ· ·fi ·˘Ù‹Ó ÙÔ˘ ·ÛıÂÓ‹ Ì·˜. ∏ ·Ó¿ÌÈÍË ÙÔ˘ ‚ÚÂÊÈÎÔ‡ Á¿Ï·ÙÔ˜ ·fi ÙË ÌËÙ¤Ú· ÁÈÓfiÙ·Ó ÛˆÛÙ¿, ·ÔÌ·ÎÚ‡ÓÔÓÙ·˜ ÙÔ ÂӉ¯fiÌÂÓÔ «‰ËÏËÙËÚ›·Û˘ ·fi ÓÂÚfi», ÂÓÒ Ë ·Ô˘Û›· ˘ÚÂÙÔ‡ Î·È ‰˘ÛÌÔÚÊÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ Î·È Ë Ê˘ÛÈÔÏÔÁÈ΋ ÂͤٷÛË ‰¤ÚÌ·ÙÔ˜, Ì·ÏÏÈÒÓ Î·È Ó˘¯ÈÒÓ ·ÔÌ·ÎÚ‡ÓÂÈ ÙÔ ÂӉ¯fiÌÂÓÔ ·ÓȉڈÙÈ΋˜ ÂÎÙÔ‰ÂÚÌÈ΋˜ ‰˘ÛÏ·Û›·˜, ‰È·Ù·Ú·¯‹ Ô˘ ÌÔÚ› Ó· ÂΉËψı› Ì ˘ÔıÚ„›· Î·È Û˘ÓÔ‰fi ˘ÂÚ˘ÚÂÍ›·, Ô˘ ‰ÂÓ ˘‹Ú¯Â ÛÙÔÓ ·ÛıÂÓ‹ Ì·˜. ∆Ô ÎÏÈÓÈÎfi ÛÂÓ¿ÚÈÔ ÙÔ˘ ‚Ú¤ÊÔ˘˜ Ô˘ ÂÚÈÁÚ¿ÊÔ˘ÌÂ, ÌÂ Û˘Ó‰˘·ÛÌfi ˘ÔÓ·ÙÚÈ·ÈÌ›·˜, ˘ÂÚηÏÈ·ÈÌ›·˜ Î·È ÌÂÙ·‚ÔÏÈ΋˜ ÔͤˆÛ˘, Â›Ó·È Û˘Ì‚·Ùfi Ì ¤ÏÏÂÈ„Ë ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ, Ô˘ ÌÔÚ› Ó· ÔÊ›ÏÂÙ·È ÛÂ Û˘ÁÁÂÓ‹ ˘ÂÚÏ·Û›· ÂÈÓÂÊÚȉ›ˆÓ, Û ˘Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi Î·È Û ·ÓÙ›ÛÙ·ÛË ÛÙË ‰Ú¿ÛË Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ ‹ „¢‰Ô¸Ô·Ï‰ÂÛÙÂÚÔÓÈÛÌfi Ù‡Ô˘ π. √È ÙÂÏÂ˘Ù·›Â˜ ‰‡Ô ÔÓÙfiÙËÙ˜ Â›Ó·È Û·ÓÈfiÙÂÚ˜. §fiÁˆ Ù˘ ÂÍ·ÈÚÂÙÈο ‰˘Û¯ÂÚÔ‡˜ ·ÈÌÔÏË„›·˜, ·Ú¯Èο ¤ÁÈÓ ̤ÙÚËÛË ÌfiÓÔ Ù˘ 17-˘‰ÚÔ͢-ÚÔÁÂÛÙÂÚfiÓ˘ Î·È Ù˘ ÎÔÚÙÈ˙fiÏ˘. √ ¤ÏÂÁ¯Ô˜ ·Ó¤‰ÂÈÍ 17-˘‰ÚÔ͢-ÚÔÁÂÛÙÂÚfiÓË 17,9 nmol/l (º.∆.: 2-6,05) Î·È ÎÔÚÙÈ˙fiÏË 241,5 nmol/l (º.∆.: 28-662). ªÂ ÙËÓ ¿ÌÂÛË ¤Ó·ÚÍË ˘‰ÚÔÎÔÚÙÈ˙fiÓ˘ Î·È ÙË ¯ÔÚ‹ÁËÛË ÎÚ˘ÛÙ·ÏÏÔÂȉÒÓ ‰È·Ï˘Ì¿ÙˆÓ Ì ¯ÏˆÚÈÔ‡¯Ô Ó¿ÙÚÈÔ, ‹Ïı ÛÙ·‰È·Î‹ ·ÔηٿÛÙ·ÛË Ù˘ ˘ÔÓ·ÙÚÈ·ÈÌ›·˜, Ì ¿ÓÔ‰Ô Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ó·ÙÚ›Ô˘ ÔÚÔ‡ ÛÙÔ 130 mEq/l Û ‰È¿ÛÙËÌ· 60 ÂÚ›Ô˘ ˆÚÒÓ.
∏ ˘„ËÏ‹ ÙÈÌ‹ 17-˘‰ÚÔ͢-ÚÔÁÂÛÙÂÚfiÓ˘ ÛÙÔÓ ·ÛıÂÓ‹ Ì·˜ Â›Ó·È ÂÓ‰ÂÈÎÙÈ΋ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÙˆÓ ÂÈÓÂÊÚȉ›ˆÓ (1-3), ·ÚfiÏÔ Ô˘ Ù· ÂÚÈÛÛfiÙÂÚ· ÚÔۂ‚ÏË̤ӷ ÓÂÔÁÓ¿ ¤¯Ô˘Ó ÛÙËÓ ÚˆÙԉȿÁÓˆÛË Û˘ÁÎÂÓÙÚÒÛÂȘ >105 nmol/l (4). ªÂ Ù· ‰Â‰Ô̤ӷ ·˘Ù¿ ¤ÁÈÓ ¿ÌÂÛ·, ÌÂÙ¿ ÙË ‰È·›ÛÙˆÛË ÙˆÓ ˘„ËÏÒÓ ÂȤ‰ˆÓ 17-˘‰ÚÔ͢-ÚÔÁÂÛÙÂÚfiÓ˘, ¯ÔÚ‹ÁËÛË ˘‰ÚÔÎÔÚÙÈ˙fiÓ˘ 25 mg ÂÓ‰ÔÊÏ‚›ˆ˜ Î·È Û˘Ó¤¯ÈÛË Ù˘ ·ÁˆÁ‹˜ ·fi ÙÔ ÛÙfiÌ· 20 mg/m2/Ë̤ڷ Û ÙÚÂȘ ‰fiÛÂȘ. ∆ËÓ ÙÚ›ÙË Ì¤Ú· ÓÔÛËÏ›·˜ ÚÔÛÙ¤ıËΠÛÙË ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹ Î·È ÊÏÔ˘ÔÚÔÎÔÚÙÈ˙fiÓË 0,05 mg/Ë̤ڷ, Ì ÛÙ·‰È·Î‹ ·‡ÍËÛË Ù˘ ‰fiÛ˘ Û 0,1 mg/Ë̤ڷ, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ¯ÔÚ‹ÁËÛË ÂÈÚfiÛıÂÙÔ˘ ¿Ï·ÙÔ˜ ÛÙÔ ‚ÚÂÊÈÎfi Á¿Ï·. ª›· ‚‰ÔÌ¿‰· ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË ıÂڷ›·˜, ¤ÁÈÓ ̤ÙÚËÛË ACTH, ·Ï‰ÔÛÙÂÚfiÓ˘, ÚÂÓ›Ó˘ Î·È DHEA-S Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈΤ˜, ÂÓÒ Ë 17-˘‰ÚÔ͢-ÚÔÁÂÛÙÂÚfiÓË ‹Ù·Ó ϤÔÓ ÂÓÙfi˜ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÙÈÌÒÓ. ∆Ô ‚Ú¤ÊÔ˜ Ô˘ ¿Ú¯ÈÛ ӷ ÛÈÙ›˙ÂÙ·È ÈηÓÔÔÈËÙÈο ÌÂÙ¿ ÙËÓ ÙÚ›ÙË Ë̤ڷ ÓÔÛËÏ›·˜ ÂÍ‹Ïı Û ¿ÚÈÛÙË ÁÂÓÈ΋ ηٿÛÙ·ÛË ÌÂÙ¿ ·fi ÓÔÛËÏ›· 3 ‚‰ÔÌ¿‰ˆÓ, Ì ‚¿ÚÔ˜ ÂÍfi‰Ô˘ 3.615 g, ˘fi ·ÁˆÁ‹ Ì ˘‰ÚÔÎÔÚÙÈ˙fiÓË Î·È ÊÏÔ˘ÔÚÔÎÔÚÙÈ˙fiÓË. ŒÎÙÔÙÂ, ÔÈ ÔÚÌfiÓ˜ 17-˘‰ÚÔ͢-ÚÔÁÂÛÙÂÚfiÓË Î·È ·Ó‰ÚÔÛÙÂÓ‰ÈfiÓË, ηıÒ˜ Î·È Ë ‰Ú·ÛÙÈÎfiÙËÙ· ÚÂÓ›Ó˘ ÔÚÔ‡, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ Ù·ÎÙÈ΋ ηٷÁÚ·Ê‹ ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ÛˆÌ·ÙÈ΋˜ ·Ó¿Ù˘Í˘ ÙÔ˘ ‚Ú¤ÊÔ˘˜, ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÁÈ· ÙËÓ ÂÎÙ›ÌËÛË Ù˘ ·ÓÙ·fiÎÚÈÛ˘ ÛÙË ıÂڷ›· ˘ÔηٿÛÙ·Û˘. ∏ ÌÂȈ̤ÓË ÌÂÙ·ÙÚÔ‹ Ù˘ 17-˘‰ÚÔ͢ÚÔÁÂÛÙÂÚfiÓ˘ Û 11-‰ÂÔ͢-ÎÔÚÙÈ˙fiÏË Â›Ó·È ˘Â‡ı˘ÓË ÁÈ· >90% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Û˘ÁÁÂÓÔ‡˜ ÂÈÓÂÊÚȉȷ΋˜ ˘ÂÚÏ·Û›·˜. ∏ ÌÂÙ·ÙÚÔ‹ ·˘Ù‹ Á›ÓÂÙ·È ·fi ÙÔ ¤Ó˙˘ÌÔ 21-˘‰ÚÔÍ˘Ï¿ÛË (CYP21A2) (1-3). ∏ ÌÂȈ̤ÓË Û‡ÓıÂÛË 11-‰ÂÔ͢-ÎÔÚÙÈ˙fiÏ˘ Ô‰ËÁ› Û ÌÂȈ̤ÓË ‚ÈÔÛ‡ÓıÂÛË ÎÔÚÙÈ˙fiÏ˘ Î·È ·ÓÙÈÚÚÔÈÛÙÈο Û ·˘ÍË̤ÓË ¤ÎÎÚÈÛË ACTH. H ÔÊÂÈÏfiÌÂÓË ÛÙËÓ ÎÔÚÙÈÎÔÙÚÔ›ÓË ‰È¤ÁÂÚÛË ÙˆÓ ÂÈÓÂÊÚȉ›ˆÓ Ô‰ËÁ› Û ·˘ÍË̤ÓË ·Ú·ÁˆÁ‹ ·Ó‰ÚÔÁfiÓˆÓ. ¢Â‰Ô̤ӷ ·fi ‰ÈÂıÓ‹ ÚÔÁÚ¿ÌÌ·Ù· ÚÒÈÌ˘ ‰È¿ÁÓˆÛ˘ Û 6,5 ÂηÙÔÌ̇ÚÈ· ÓÂÔÁÓ¿ ‰›ÓÔ˘Ó ÌÈ· ›وÛË ÂÚ›Ô˘ 1 ÛÙ· 15.000 ˙ÒÓÙ· ÓÂÔÁ¤ÓÓËÙ·, Ì ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ·Ó¿ÏÔÁ· Ì ÙË ¯ÒÚ· Î·È ÙÔÓ ÏËı˘ÛÌfi ÌÂϤÙ˘ (5). √È
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¶·È‰È·ÙÚÈ΋ 2009;72:66,71-73
Pediatric Jan-Feb 09
16-03-09
72
14:56
™ÂÏ›‰·72
∫§π¡π∫√ ∫√Àπ∑ ·ÛıÂÓ›˜ Ì ÎÏ·ÛÈÎÔ‡ Ù‡Ô˘ Û˘ÁÁÂÓ‹ ÂÈÓÂÊÚȉȷ΋ ˘ÂÚÏ·Û›· ÏfiÁˆ ¤ÏÏÂȄ˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ Ù˘Èο ÂÌÊ·Ó›˙ÔÓÙ·È Î·Ù¿ ÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô ‹ Ï›ÁÔ ÌÂÙ¿, Ì ·Ó·Ú΋ ÚfiÛÏË„Ë ‚¿ÚÔ˘˜, ·›Û¯Ó·ÛË, ·Ê˘‰¿ÙˆÛË, Ì ‹ ¯ˆÚ›˜ ·ÒÏÂÈ· ¿Ï·ÙÔ˜, ‹ ÛÙË ÓËȷ΋ ËÏÈΛ· Ì ·ÚÚÂÓÔÔ›ËÛË. ∆· ı‹Ï· ‚Ú¤ÊË ÂÌÊ·Ó›˙Ô˘Ó ·ÌÊ›‚ÔÏ· ¤Íˆ ÁÂÓÓËÙÈο fiÚÁ·Ó· (·ÚÚÂÓÔÔ›ËÛË ¤Íˆ ÁÂÓÓËÙÈÎÒÓ ÔÚÁ¿ÓˆÓ). ∆· ·ÁfiÚÈ· ÂÌÊ·Ó›˙ÔÓÙ·È Ê˘ÛÈÔÏÔÁÈο ‹ ÌÔÚ› Ó· ¤¯Ô˘Ó ·˘ÍË̤ÓË ˘¤Ú¯ÚˆÛË ÙÔ˘ ÔÛ¯¤Ô˘ Î·È ÌÂÁ¿ÏÔ ¤Ô˜. ¶ÂÚ›Ô˘ ÙÔ 67% ÙˆÓ ·ÛıÂÓÒÓ Ì ÎÏ·ÛÈ΋ ¤ÏÏÂÈ„Ë 21-˘‰ÚÔÍ˘Ï¿Û˘ ÂÌÊ·Ó›˙ÂÈ ·ÒÏÂÈ· ¿Ï·ÙÔ˜, ÏfiÁˆ ¤ÏÏÂȄ˘ ·Ï‰ÔÛÙÂÚfiÓ˘, ÂÓÒ ÙÔ ˘fiÏÔÈÔ ¤Ó· ÙÚ›ÙÔ ÂÌÊ·Ó›˙ÂÈ ÙË ÌÔÚÊ‹ Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ÌfiÓÔ ·fi ·ÚÚÂÓÔÔ›ËÛË. √ ÛÙfi¯Ô˜ Ù˘ ·Ú¯È΋˜ ıÂڷ›·˜ Û ÂÈÓÂÊÚȉȷ΋ ÎÚ›ÛË Â›Ó·È Ë ÁÚ‹ÁÔÚË ‰ÈfiÚıˆÛË Ù˘ ·Ê˘‰¿ÙˆÛ˘ Î·È Ù˘ ˘fiÙ·Û˘, Ë ÛÙ·‰È·Î‹ ·ÔηٿÛÙ·ÛË Ù˘ ˘ÔÓ·ÙÚÈ·ÈÌ›·˜ Î·È Ë ‰ÈfiÚıˆÛË Ù˘ ¤ÏÏÂȄ˘ ÎÔÚÙÈ˙fiÏ˘. ªÈ· ·Ú¯È΋ ‰fiÛË stress ˘‰ÚÔÎÔÚÙÈ˙fiÓ˘ 50-100 mg/m2 (Ù˘È΋ ÓÂÔÁÓÈ΋ ‰fiÛË 25 mg) Ú¤ÂÈ Ó· ·ÎÔÏÔ˘ıÂ›Ù·È ·fi ¯ÔÚ‹ÁËÛË ËÌÂÚ‹ÛÈˆÓ ‰fiÛÂˆÓ 50100 mg/m2 Û ‰È·ÈÚÂ̤Ó˜ ‰fiÛÂȘ Î·È Ì¤¯ÚÈ ÙË ÛÙ·ıÂÚÔÔ›ËÛË ÙÔ˘ ÓÂÔÁÓÔ‡ Î·È ÙËÓ ¤Ó·ÚÍË ÈηÓÔÔÈËÙÈ΋˜ Û›ÙÈÛ˘. ™ÙËÓ ÔÍ›· Ê¿ÛË Ô˘ ¯ÔÚËÁÂ›Ù·È ˘‰ÚÔÎÔÚÙÈ˙fiÓË Û ‰fiÛÂȘ stress ‰ÂÓ Â›Ó·È ÙÂÏ›ˆ˜ ··Ú·›ÙËÙË Ë ¯Ú‹ÛË ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ, ·ÚfiÏÔ Ô˘ ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ·È‰ÔÂÓ‰ÔÎÚÈÓÔÏfiÁÔÈ Ù· ÍÂÎÈÓÔ‡Ó ·Ì¤Ûˆ˜ Û ‰fiÛË 0,15 mg/m2/Ë̤ڷ. ™ÙË Û˘Ó¤¯ÂÈ· ¯ÔÚËÁÂ›Ù·È ˘‰ÚÔÎÔÚÙÈ˙fiÓË Û ‰fiÛË 12-18 mg/m2/Ë̤ڷ Û ‰È·ÈÚÂ̤Ó˜ ‰fiÛÂȘ Î·È Û˘Ó¯›˙ÂÙ·È Ë ·ÁˆÁ‹ Ì ÊÏÔ˘ÔÚÔÎÔÚÙÈ˙fiÓË. H ·Ó·Ú΋˜ ˘ÔηٿÛÙ·ÛË ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ̷ÎÚÔ¯ÚfiÓÈ· Ì›ˆÛË ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘, ¯ˆÚ›˜ ȉȷ›ÙÂÚ· ÎÏÈÓÈο Â˘Ú‹Ì·Ù·, ÌÂ Û˘ÓÔ‰fi ˘ÂÚ·Ú·ÁˆÁ‹ ÂÈÓÂÊÚȉȷÎÒÓ ·Ó‰ÚÔÁfiÓˆÓ ÏfiÁˆ ˘ÂÚ·Ú·ÁˆÁ‹˜ ÚÂÓ›Ó˘ Î·È ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ Ô˘ ‰ÈÂÁ›ÚÔ˘Ó ÙËÓ ÂÈÓÂÊÚȉȷ΋ ÛÙÂÚÔÂȉÔÁ¤ÓÂÛË (6). °È· ÙÔ˘˜ ÏfiÁÔ˘˜ ·˘ÙÔ‡˜, Ù· ·Ï·ÙÔÎÔÚÙÈÎÔÂȉ‹ Â›Ó·È ˆÊ¤ÏÈÌ· ÛÙËÓ ÎÏ·ÛÛÈ΋ ¤ÏÏÂÈ„Ë 21-˘‰ÚÔÍ˘Ï¿Û˘, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ·Ó ·˘Ù‹ Û˘Óԉ‡ÂÙ·È ‹ fi¯È ·fi ·ÒÏÂÈ· ¿Ï·ÙÔ˜. ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ Û˘ÁÁÂÓÔ‡˜ ÂÈÓÂÊÚȉȷ΋˜ ˘ÂÚÏ·Û›·˜ ÏfiÁˆ ¤ÏÏÂȄ˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ ÂÓ¤¯ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ˘ÂÚıÂڷ›·˜, Ì ÂÌÊ¿ÓÈÛË È·ÙÚÔÁÂÓÔ‡˜ Û˘Ó‰ÚfiÌÔ˘ Cushing Î·È Î·ı˘ÛÙ¤ÚËÛ˘ Ù˘ ·Ó¿Ù˘Í˘. ∏ ÌË ÎÏ·ÛÈ΋ ‹ fi„ÈÌË ¤ÏÏÂÈ„Ë 21-˘‰ÚÔÍ˘Ï¿Û˘ ÂÌÊ·Ó›˙ÂÙ·È ÌÂÙ·ÁÂÓ¤ÛÙÂÚ·, Ì ÎÏÈÓÈο
Paediatriki 2009;72:66,71-73
ÛËÌ›· ÂÚ›ÛÛÂÈ·˜ ·Ó‰ÚÔÁfiÓˆÓ Î·È ¯ˆÚ›˜ ÈÛÙÔÚÈÎfi ·ÚÚÂÓÔÔ›ËÛ˘ ÙˆÓ ¤Íˆ ÁÂÓÓËÙÈÎÒÓ ÔÚÁ¿ÓˆÓ ÛÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô (7). ∫ÏÈÓÈο ÛËÌ›· Î·È Û˘ÌÙÒÌ·Ù¿ Ù˘ Â›Ó·È Ë ÚÒÈÌË ‹‚Ë, Ë ÚÔ¯ˆÚË̤ÓË ÔÛÙÈ΋ ËÏÈΛ·, Ë ˘ÂÚÙÚ›¯ˆÛË, ÔÈ ‰È·Ù·Ú·¯¤˜ ÂÚÈfi‰Ô˘, Ë ·ÎÌ‹ Î·È Ë ˘ÔÁÔÓÈÌfiÙËÙ·, ·ÚfiÏÔ Ô˘ ·ÚÎÂÙÔ› ·ÛıÂÓ›˜ ·Ú·Ì¤ÓÔ˘Ó ·Û˘Ìو̷ÙÈÎÔ›. ∏ ¤ÏÏÂÈ„Ë 11-‚-˘‰ÚÔÍ˘Ï¿Û˘ (CYP11B1) Â›Ó·È Ë ‰Â‡ÙÂÚË ÛÂ Û˘¯ÓfiÙËÙ· ·ÈÙ›· Û˘ÁÁÂÓÔ‡˜ ÂÈÓÂÊÚȉȷ΋˜ ˘ÂÚÏ·Û›·˜, ηıÒ˜ ¢ı‡ÓÂÙ·È ÁÈ· ÙÔ 5-8% ÙˆÓ ÂÚÈÙÒÛˆÓ, Ì ›وÛË 1 ÛÙȘ 100.000 ÁÂÓÓ‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁ¤ÓÓËÙˆÓ (1-3). ∆Ô ÂÓ˙˘ÌÈÎfi ¤ÏÏÂÈÌÌ· ÚÔηÏ› Ì›ˆÛË ÛÙË ÌÂÙ·ÙÚÔ‹ Ù˘ 11-‰ÂÔ͢-ÎÔÚÙÈ˙fiÏ˘ Î·È 11-‰ÂÔ͢-ÎÔÚÙÈÎÔÛÙÂÚfiÓ˘ Û ÎÔÚÙÈ˙fiÏË Î·È ÎÔÚÈÎÔÛÙÂÚfiÓË, ·ÓÙ›ÛÙÔȯ·, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·ÓÙÈÚÚÔÈÛÙÈ΋ ·‡ÍËÛË Ù˘ ÎÔÚÙÈÎÔÙÚÔ›Ó˘ Î·È ÙËÓ Â·ÎfiÏÔ˘ıË ·˘ÍË̤ÓË ·Ú·ÁˆÁ‹ ÂÈÓÂÊÚȉȷÎÒÓ ·Ó‰ÚÔÁfiÓˆÓ. √È ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ Ù˘ ¤ÏÏÂȄ˘ 11-‚-˘‰ÚÔÍ˘Ï¿Û˘ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· Ù˘ ÂÚ›ÛÛÂÈ·˜ ·Ó‰ÚÔÁfiÓˆÓ Î·È Ù˘ ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÈ΋˜ ‰Ú¿Û˘ Ù˘ 11-‰ÂÔ͢-ÎÔÚÙÈÎÔÛÙÂÚfiÓ˘. ∏ ÙÂÏÂ˘Ù·›· ÌÔÚ› Ó· ÂΉËψı› Ì ˘ÔηÏÈ·ÈÌ›· Î·È ˘¤ÚÙ·ÛË Î·È ·˘Ù¿ ÙË ‰È·ÎÚ›ÓÔ˘Ó ·fi ÙË Û˘¯ÓfiÙÂÚË ¤ÏÏÂÈ„Ë 21-˘‰ÚÔÍ˘Ï¿Û˘. √ ˘Ô·Ï‰ÔÛÙÂÚÔÓÈÛÌfi˜, Ô˘ ı· Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏËÊı› ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ ·ÛıÂÓ‹ Ì·˜, ÔÊ›ÏÂÙ·È Û ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ¤Ó˙˘ÌÔ CYP11B2 (Û˘ÓıÂÙ¿ÛË ·Ï‰ÔÛÙÂÚfiÓ˘), ÌÈ· Û¿ÓÈ· ‰È·Ù·Ú·¯‹ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ‰‡Ô ˘fiÙ˘Ô˘˜, ·Ó¿ÏÔÁ· Ì ٷ ›‰· ·Ï‰ÔÛÙÂÚfiÓ˘ Î·È ÙˆÓ ÚÔ‰ÚfiÌˆÓ Ù˘. ∞ÛıÂÓ›˜ Ì ¤ÏÏÂÈ„Ë ÌÂı˘Ï-ÔÍÂȉ¿Û˘ ÎÔÚÙÈÎÔÛÙÂÚfiÓ˘ Ù‡Ô˘ π ¤¯Ô˘Ó ·Ó‚·Ṳ̂ӷ ›‰· ÎÔÚÙÈÎÔÛÙÂÚfiÓ˘ Î·È ¯·ÌËÏ¿ ›‰· 18-˘‰ÚÔ͢-ÎÔÚÙÈÎÔÛÙÂÚfiÓ˘ Î·È ·Ï‰ÔÛÙÂÚfiÓ˘. ∞ÓÙÈı¤Ùˆ˜, ÔÈ ·ÛıÂÓ›˜ Ì ¤ÏÏÂÈ„Ë ÌÂı˘Ï-ÔÍÂȉ¿Û˘ ÎÔÚÙÈÎÔÛÙÂÚfiÓ˘ Ù‡Ô˘ ππ ¤¯Ô˘Ó ˘„ËÏ‹ 18-˘‰ÚÔ͢ÎÔÚÙÈÎÔÛÙÂÚfiÓË, ÙËÓ ¿ÌÂÛË Úfi‰ÚÔÌË Ô˘Û›· Ù˘ ·Ï‰ÔÛÙÂÚfiÓ˘ (8). √ „¢‰Ô¸Ô·Ï‰ÂÛÙÂÚÔÓÈÛÌfi˜ Ù‡Ô˘ π, Ô˘ ›Û˘ ı· Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏËÊı› ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË, ¤¯ÂÈ ·Ó·ÁÓˆÚÈÛÙ› ˆ˜ ¤Ó· ÂÙÂÚÔÁÂÓ¤˜ Û‡Ó‰ÚÔÌÔ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ˘Ï¿¯ÈÛÙÔ ‰‡Ô ÎÏÈÓÈο ‰È·ÎÚÈÙ¤˜ ÔÓÙfiÙËÙ˜ Ì ÓÂÊÚÈ΋ ‹ ÔÏ˘ÔÚÁ·ÓÈ΋ Û˘ÌÌÂÙÔ¯‹, ·ÓÙ›ÛÙÔȯ·. ∆˘Èο ÂÌÊ·Ó›˙ÔÓÙ·È Û‡ÓÙÔÌ· ÌÂÙ¿ ÙË Á¤ÓÓËÛË, Ì ÛËÌ›· ¤ÏÏÂȄ˘ ·Ï·ÙÔÎÔÚÙÈÎÔÂȉÒÓ, ·ÏÏ¿ Ì ·ıÔÏÔÁÈο ˘„ËϤ˜ ÙÈ̤˜ Ï¿ÛÌ·ÙÔ˜ ·Ï‰ÔÛÙÂÚfiÓ˘ Î·È ÚÂÓ›Ó˘. ∆· ÛËÌ›· Î·È Û˘ÌÙÒÌ·Ù· ·ÓÙ›ÛÙ·Û˘ ÛÙËÓ ·Ï‰ÔÛÙÂÚfiÓË
Pediatric Jan-Feb 09
16-03-09
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CLINICAL QUIZ ˘Ô¯ˆÚÔ‡Ó Ì ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘ Û ÔÏÏÔ‡˜ ·ÛıÂÓ›˜, ÌÂÚÈÎÔ› fï˜ ηٷϋÁÔ˘Ó ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ· ·fi ˘ÂÚηÏÈ·ÈÌ›· (8). ªÂÚÈΤ˜ ¯ÒÚ˜ ÂÊ·ÚÌfi˙Ô˘Ó ÚÔÁÚ¿ÌÌ·Ù· ÚÒÈÌ˘ ‰È¿ÁÓˆÛ˘ Ù˘ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÙˆÓ ÂÈÓÂÊÚȉ›ˆÓ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, ‰Â‰Ô̤ÓÔ˘ fiÙÈ Â›Ó·È Ì›· ·fi ÙȘ Û˘¯ÓfiÙÂÚ˜ ÎÏËÚÔÓÔÌÔ‡ÌÂÓ˜ ‰È·Ù·Ú·¯¤˜ Ì ·˘ÙÔÛˆÌÈÎfi ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú·. ∆· ÚÔÁÚ¿ÌÌ·Ù· ·˘Ù¿ ÌÂÈÒÓÔ˘Ó ÙËÓ Èı·ÓfiÙËÙ· ÚÔÛ¤Ï¢Û˘ ÓÂÔÁÓÒÓ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô Ì ‚·ÚÈ¿ ·Ê˘‰¿ÙˆÛË Î·È ·ÒÏÂÈ· ¿Ï·ÙÔ˜ Î·È Èı·ÓfiÓ ÌÂÈÒÓÔ˘Ó Î·È ÙË ıÓËÙfiÙËÙ· ÏfiÁˆ ηı˘ÛÙÂÚË̤Ó˘ ‰È¿ÁÓˆÛ˘. ™˘ÌÂÚ·ÛÌ·ÙÈο, οı ÓÂÔÁÓfi ‹ ‚Ú¤ÊÔ˜ ÔÏ›ÁˆÓ ‚‰ÔÌ¿‰ˆÓ Ô˘ ÂÌÊ·Ó›˙ÂÙ·È Ì ˘ÔıÚ„›·, ·Ó·Ú΋ ·Ó¿Ù˘ÍË, ·Ê˘‰¿ÙˆÛË Î·È ÂÌÂÙÔ‡˜ ı· Ú¤ÂÈ Ó· ÂϤÁ¯ÂÙ·È ÁÈ· ËÏÂÎÙÚÔÏ˘ÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ηÈ, ÂÊfiÛÔÓ ˘¿Ú¯ÂÈ ˘ÔÓ·ÙÚÈ·ÈÌ›· Î·È ˘ÂÚηÏÈ·ÈÌ›·, Ó· Á›ÓÂÙ·È ¿ÌÂÛ· ̤ÙÚËÛË 17-˘‰ÚÔ͢-ÚÔÁÂÛÙÂÚfiÓ˘, ηıÒ˜ Î·È ÎÔÚÙÈ˙fiÏ˘, 11-‰ÂÔ͢-ÎÔÚÙÈ˙fiÏ˘, 17˘‰ÚÔ͢-ÚÂÁÓÂÓÔÏfiÓ˘ Î·È ·Ó‰ÚÔÛÙÂÓ‰ÈfiÓ˘ ÁÈ· ·ÔÎÏÂÈÛÌfi Û˘ÁÁÂÓÔ‡˜ ÂÈÓÂÊÚȉȷ΋˜ ˘ÂÚÏ·Û›·˜ Î·È Î·ıÔÚÈÛÌfi ÙÔ˘ ÂÓ˙˘ÌÈÎÔ‡ ÂÏÏ›ÌÌ·ÙÔ˜.
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µÈ‚ÏÈÔÁÚ·Ê›· 1. Merke DP, Bornstein SR. Congenital adrenal hyperplasia. Lancet 2005;365:2125-2136. 2. Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med 2003;349:776-788. 3. Clayton PE, Miller WL, Oberfield SE, Ritzén EM, Sippell WG, Speiser PW; ESPE/LWPES CAH Working Group. Consensus statement on 21-hydroxylase deficiency from the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society. Horm Res 2002;58:188-195. 4. Witchel SF, Nayak S, Suda-Hartman M, Lee PA. Newborn screening for 21-hydroxylase deficiency: results of CYP21 molecular genetic analysis. J Pediatr 1997;131:328-331. 5. Pang S, Clark A. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Newborn screening and its relationship to the diagnosis and treatment of the disorder. Screening 1993;2:105-139. 6. Schaison G, Couzinet B, Gourmelen M, Elkik F, Bougneres P. Angiotensin and adrenal steroidogenesis: study of 21-hydroxylase-deficient congenital adrenal hyperplasia. J Clin Endocrinol Metab 1980;51: 1390-1394. 7. Kohn B, Levine LS, Pollack MS, Pang S, Lorenzen F, Levy D, et al. Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia. J Clin Endocrinol Metab 1982;55:817-827. 8. White PC. Abnormalities of aldosterone synthesis and action in children. Curr Opin Pediatr 1997;9: 424-430.
¶·È‰È·ÙÚÈ΋ 2009;72:66,71-73