Παιδιατρική | Τόμος 69 • Τεύχος 6 • Νοέμβριος - Δεκέμβριος 2006 by E-chlld

Exof Pediatr Nov-Dec 06

06-12-06

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TﬁÌÔ˜ 69 ñ ∆Â‡¯Ô˜ 6 ñ No¤Ì‚ÚÈÔ˜-¢ÂÎ¤Ì‚ÚÈÔ˜ 2006 ¶·È‰È·ÙÚÈÎ‹ ñ TﬁÌÔ˜ 69 ñ ∆Â‡¯Ô˜ 6 ñ ¡Ô¤Ì‚ÚÈÔ˜-¢ÂÎ¤Ì‚ÚÈÔ˜ 2006 Volume 69 ñ Number 6 ñ ¡ovember-December 2006 ISSN 0377-2551

www.paediatriki.edu.gr

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EÙ‹ÛÈ· ™˘Ó‰ÚÔÌ‹: 40 € EÈ‰ÈÎÂ˘ﬁÌÂÓÔÈ, ºÔÈÙËÙ¤˜: 20 € ∫ˆ‰ÈÎﬁ˜ ¢ÈÂ‡ı˘ÓÛË˜ ∂ÔÙÂ›·˜ ªª∂: 3889

ISSN 0377-2551

409 O ÚfiÏÔ˜ ÙË˜ ·fiÙˆÛË˜ ÛÙË ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ· µ. ¢ÚfiÛÔ˘-∞Á·Î›‰Ô˘, ∂. ™ˆÙËÚ›‰Ô˘ 417 O Û˘Ó‰˘·ÛÌfi˜ ÂÈÛÓÂfiÌÂÓˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ Î·È ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÛÙË ıÂÚ·Â›· ÙÔ˘ ·È‰ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ ª.µ. ∞ÓıÚ·ÎfiÔ˘ÏÔ˜, ∫.¡. ¶Ú›ÊÙË˜ 425 ∞ÓÙÈÊÏÂÁÌÔÓÒ‰Ë˜ ·ÁˆÁ‹ ˘ÔÙÚÔÈ¿˙ÔÓÙÔ˜ Û˘ÚÈÁÌÔ‡ ÛÙ· ¤ÓÙÂ ÚÒÙ· ¯ÚfiÓÈ· ÙË˜ ˙ˆ‹˜ ª.µ. ∞ÓıÚ·ÎfiÔ˘ÏÔ˜, º. ∫˘Ú‚·Û›ÏË˜, π.¡. ∆Û·Ó¿Î·˜ ∂ƒ∂À¡∏∆π∫∂™ ∂ƒ°∞™π∂™ 432 H Û˘Ì‚ÔÏ‹ ÙË˜ ÚÒÈÌË˜ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ·˘ÙfiÓÔÌÔ˘ ÓÂ˘ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Î·È ·Ú·ÌÔÓ‹ ˘„ËÏ‹˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜ Î·Ù¿ ÙË Ó‡ÎÙ· ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ ÛÂ ÂÊ‹‚Ô˘˜ ÌÂ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 1 ∫. K·Ú·‚·Ó¿ÎË, °. ∫·˙È¿ÓË˜, Ã. ∫·Ú·ÁÈ¿ÓÓË, ∞. ™Î·Ú‰Ô‡ÙÛÔ˘, ∫. ∫·ÎÏ¤·˜, ∞. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜ 440 ™˘Û¯¤ÙÈÛË Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜ Î·È ÎÏÈÓÈÎ‹˜ Î·Ù¿ÛÙ·ÛË˜ ·ÛıÂÓÒÓ ÌÂ Î˘ÛÙÈÎ‹ ›ÓˆÛË ∆. ªÔ‡‰ÈÔ˘, ∞. °·ÏÏ‹-∆ÛÈÓÔÔ‡ÏÔ˘, ∂. µ·Ì‚·ÎÔ‡‰Ë˜, ™. ¡Ô‡ÛÈ·-∞Ú‚·ÓÈÙ¿ÎË ∂¡¢π∞º∂ƒ√À™∂™ ¶∂ƒπ¶∆ø™∂π™ 447 °ÂÓÂÙÈÎfi˜ ÎÏÈÓÈÎÔÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÛÂ ÔÈÎÔÁ¤ÓÂÈ· ÌÂ ÎÏÈÓÈÎ‹ ÂÙÂÚÔÁ¤ÓÂÈ· Û˘Ó‰ÚfiÌÔ˘ Noonan ™. ∫›ÙÛÈÔ˘-∆˙¤ÏË, Õ. ¶··‰ÔÔ‡ÏÔ˘, ∞. •·˚‰¿Ú·, °. ¶··‰fiÔ˘ÏÔ˜, ∞.-ª. ª·ÁÈ¿ÎÔ˘, ∞. ∫ÔÏÈ·Ï¤ÍË, ∞. ª·‡ÚÔ˘, ∂. ∫·Ó·‚¿ÎË˜, ¶. ¡ÈÎÔÏ·˝‰Ô˘

452 ∞ÓÙÈÌÂÙÒÈÛË ÙË˜ ÔÛÙÂÔfiÚˆÛË˜ Î·È ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ ÌÂ ‰ÈÓ·ÙÚÈÔ‡¯Ô ·ÌÈ‰ÚÔÓ¿ÙË ÛÂ ‚Ú¤ÊÔ˜ ÌÂ ·ÙÂÏ‹ ÔÛÙÂÔÁ¤ÓÂÛË Ù‡Ô˘ IV ª. ¶··Ê˘Ï·ÎÙÔ‡, ¶. §··ÙÛ¿ÓË˜, ¶. ¶Ô˘ÏfiÔ˘ÏÔ˜, M.B. Petersen, ∫. ªÈ¯·Ï·Î¿ÎÔ˘, ∫. ¶ÚÔ‡ÓÙ˙Ô˘-∫·ÛÛÈÔ‡ 458 ¶·Ú·ÛÔÓ‰˘ÏÈÎfi ÂÍˆÔÛÙÈÎfi Û¿ÚÎˆÌ· ÙÔ˘ Ewing: ¶ÂÚÈÁÚ·Ê‹ 2 ÂÚÈÙÒÛÂˆÓ º. ∞ı·Ó·ÛÈ¿‰Ô˘, ∞. ∆Ú·ÁÈ·ÓÓ›‰Ë˜, ª. ∫Ô‡ÚÙË, £. ¶··ÁÂˆÚÁ›Ô˘, ¶. Ã˘Ù›ÚÔÁÏÔ˘, µ. ∫ÔÓÙfiÔ˘ÏÔ˜, ∞. ∫·ÏÔÁÂÚ¿, ∞. ¢ÚÂ‚ÂÏ¤ÁÎ·˜ 463 °ÂÓÓ‹ÛÂÈ˜ ·È‰ÈÒÓ ÌÂ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜ ÌÂÙ¿ ·fi ˘Ô‚ÔËıÔ‡ÌÂÓË ÁÔÓÈÌÔÔ›ËÛË π. ∆Û¿ÙÚ·, ∫. ∫·Ú·ÛÌ¿ÓË˜, º. µ·ÚÂÏ¿˜, Ã. ∆Û¿ÓÙ·ÏË, ∞. ∫Ô‡ÛË, ª. ∞ı·Ó·Û›Ô˘ ¶ƒ∞∫∆π∫O £∂ª∞ 468 √‰ËÁ›Â˜ ÁÈ· ¿ÛÎËÛË ÛÂ ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ ÌÂ Û˘ÁÁÂÓÂ›˜ ‹ Â›ÎÙËÙÂ˜ ·ı‹ÛÂÈ˜ ÙÔ˘ Î˘ÎÏÔÊÔÚÈÎÔ‡ ¢. °ÂˆÚÁ·ÎfiÔ˘ÏÔ˜, °. ¶··‰fiÔ˘ÏÔ˜ 478 µπµ§π√¶∞ƒ√À™π∞™∏ «∫ÏÈÓÈÎ‹ ¶·È‰È·ÙÚÈÎ‹» 479 ∫§π¡π∫√ ∫√Àπ∑ ∞. ¶··‰ÔÔ‡ÏÔ˘, °. ƒÔ˘Ì¿ÓË, §. ™Ù·ÌÔÁÈ¿ÓÓÔ˘, ∂. ∫·ÙÛ·ÚÔ‡-¶ÂÎÙ·Û›‰Ë 480 ¡∂∞ ∞¶√ ∆√ ¢π∞¢π∫∆À√ ™‡Á¯ÚÔÓ· ËÏÂÎÙÚÔÓÈÎ¿ ÓËÈ·ÁˆÁÂ›· ¡. ¶··‰fiÔ˘ÏÔ˜ 483 ∂Àƒ∂∆∏ƒπ√ ∫ƒπ∆ø¡ ∆√À ∆√ª√À 69 484 ∂Àƒ∂∆∏ƒπ√ ™À°°ƒ∞º∂ø¡ ∆√À ∆√ª√À 69 486 ∂Àƒ∂∆∏ƒπ√ §∂•∂ø¡ ∫§∂π¢πø¡ ∆√À ∆√ª√À 69

Paediatriki Volume 69 ñ Number 6 ñ November-December 2006 Bimonthly Publication of the Greek Paediatric Society President A. Constantopoulos Editorial Board Editor-in-Chief C. Stefanidis Members P. Augoustides-Savvopoulou H. Antonopoulou A. Vazeou-Gerasimidi G. Varlamis M. Kanariou ∂. Katsarou-Pectasides A. Kattamis Ch. Costalos N. Papadopoulos ∞. Papadopoulou A. Siamopoulou-Mavridou M. Tsolia Manuscript Editing Greek Editing F. Mavroidi English Editing S. Nakou

Contents REVIEW ARTICLES 409 The role of apoptosis in diabetic embryopathy V. Drossou-Agakidou, E. Sotiridou 417 Combination therapy with inhaled corticosteroids and long-acting b2-agonists in childhood asthma M. B. Anthracopoulos, K. N. Priftis 425 Anti-inflammatory therapy of recurrent wheezing during the first five years of life M. B. Anthracopoulos, F. Kyrvassilis, J. N. Tsanakas ORIGINAL ARTICLES 432 The contribution of nocturnal blood pressure change and autonomic dysfunction in the pathogenesis of microalbuminuria in adolescents with type 1 diabetes mellitus K. Karavanaki, G. Kazianis, C. Karagianni, A. Skardoutsou, C. Kakleas, A. Constantopoulos

452 Symptomatic pamidronate treatment of an infant with osteogenesis imperfecta type IV M. Papaphylactou, P. Lapatsanis, P. Poulopoulos, M. B. Petersen, K. Michalakakou, K. Prountzou-Kassiou 458 Extraskeletal Ewing’s sarkoma: report of 2 cases F. Athanassiadou, A. Tragiannidis, M. Kourti, T. Papageorgiou, P. Chytiroglou, V. Kontopoulos, A. Kalogera, A. Drevelegas 463 Birth of children with hemoglobinopathies following use of IVF I. Tsatra, K. Karasmanis, F. Varelas, C. Tsantali, A. Koussi, M. Athanassiou PRACTICAL ISSUE 468 Exercise recommendations for children and adolescents with congenital and acquired cardiovascular disorders D. Georgakopoulos, G. Papadopoulos

Publisher K. Griveas Publishing Coordinator SCIENTIFIC PUBLICATIONS Ltd 3 Artemidos str. GR - 151 25, Maroussi Tel.: +30 210 87 78 810 Fax: +30 210 87 78 822 Owner Greek Paediatric Society© 92 Michalakopoulou str. 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

440 Relation of resting energy expenditure with the clinical condition in cystic fibrosis patients T. Moudiou, A. Galli-Tsinopoulou, E. Vamvacoudis, S. Noussia-Arvanitakis

478 BOOK PRESENTATION 479 CLINICAL QUIZ A. Papadopoulou, G. Roumani, L. Stamogiannou, E. Katsarou-Pectasidi

CASE REPORTS 480 NEWS FROM THE INTERNET 447 Molecular, clinical and laboratory investigation in a Noonan syndrome family presenting with clinical variability S. Kitsiou-Tzeli, A. Papadopoulou, A. Xaidara, G. Papadopoulos, A.-M.- Magiakou, A. Kolialexi, A. Mavrou, E. Kanavakis, P. Nikolaidou

Modern e-kindergardens N. Papadopoulos 483 REVIEWERS OF MANUSCRIPTS INDEX, VOLUME 69 484 AUTHORS INDEX, VOLUME 69 486 SUBJECT INDEX, VOLUME 69

√¢∏°π∂™ ¶ƒ√™ ∆√À™ ™À°°ƒ∞º∂π™ A. °ÂÓÈÎ¤˜ ¶ÏËÚÔÊÔÚ›Â˜ ∆Ô ÂÚÈÔ‰ÈÎfi “¶·È‰È·ÙÚÈÎ‹” Â›Ó·È Ë ÂÈÛÙËÌÔÓÈÎ‹ ¤Î‰ÔÛË Î·È È‰ÈÔÎÙËÛ›· ÙË˜ EÏÏËÓÈÎ‹˜ ¶·È‰È·ÙÚÈÎ‹˜ EÙ·ÈÚÂ›·˜, Ô˘ ‰È·Ó¤ÌÂÙ·È ÛÙ· Ì¤ÏË ÙË˜. Œ¯ÂÈ ˆ˜ ‚·ÛÈÎÔ‡˜ ÛÙfi¯Ô˘˜ ÙËÓ ·ÔÙ‡ˆÛË ÙÔ˘ ·È‰È·ÙÚÈÎÔ‡ ÂÈÛÙËÌÔÓÈÎÔ‡ ¤ÚÁÔ˘ Î·È ÙË Û˘ÓÂ¯‹ ÂÓËÌ¤ÚˆÛË ÙˆÓ ¶·È‰È¿ÙÚˆÓ. °È· ÙÔ ÛÎÔfi ·˘Ùfi ‰¤¯ÂÙ·È ÁÈ· ‰ËÌÔÛ›Â˘ÛË ÔÈÎÈÏ›· ¿ÚıÚˆÓ Î·È Û˘ÁÎÂÎÚÈÌ¤Ó·: 1. ÕÚıÚ· Û‡ÓÙ·ÍË˜ (ÌÂÙ¿ ·fi ÚfiÛÎÏËÛË ÙË˜ ™˘ÓÙ·ÎÙÈÎ‹˜ EÈÙÚÔ‹˜). 2. ∞Ó·ÛÎÔ‹ÛÂÈ˜. 3. µÚ·‚Â˘Ì¤ÓÂ˜ ÂÚÁ·Û›Â˜. 4. ∂ÚÂ˘ÓËÙÈÎ¤˜ ÌÂÏ¤ÙÂ˜. 5. ∫ÏÈÓÈÎ¿ ∫Ô˘›˙. 6. ∂ÈÏÂÁÌ¤ÓÂ˜ Û˘˙ËÙ‹ÛÂÈ˜ ÛÙÚÔÁÁ˘ÏÒÓ ÙÚ·Â˙ÒÓ. 7. ∂›Î·ÈÚ· ı¤Ì·Ù·. 8. £¤Ì·Ù· ÂÎ·›‰Â˘ÛË˜ Î·È ÔÚÁ¿ÓˆÛË˜ ˘ÁÂ›·˜. 9. ∂Ó‰È·Ê¤ÚÔ˘ÛÂ˜ ÂÚÈÙÒÛÂÈ˜. 10. ™‡ÓÙÔÌ· Ó¤·. 11. µÚ·¯Â›Â˜ ‰ËÌÔÛÈÂ‡ÛÂÈ˜. 12. ∂ÈÛÙÔÏ¤˜ ÚÔ˜ ÙË Û‡ÓÙ·ÍË. 13. ¶ÂÚÈÏ‹„ÂÈ˜ ÙË˜ ‚È‚ÏÈÔÁÚ·Ê›·˜. 14. ∞Ó·ÎÔÈÓÒÛÂÈ˜ ÚÔÛÂ¯ÒÓ Û˘ÓÂ‰Ú›ˆÓ Î·È ÂÈÛÙËÌÔÓÈÎÒÓ ÂÎ‰ËÏÒÛÂˆÓ 15. ∞Ó·ÊÔÚ¤˜ Î·È ÎÚÈÙÈÎ‹ Ó¤ˆÓ ÂÎ‰fiÛÂˆÓ, ÂÏÏËÓÈÎÒÓ Î·È Í¤ÓˆÓ, ·È‰È·ÙÚÈÎÔ‡ ÂÓ‰È·Ê¤ÚÔÓÙÔ˜. H ™˘ÓÙ·ÎÙÈÎ‹ EÈÙÚÔ‹ ‰È·ÙËÚÂ› ÙÔ ‰ÈÎ·›ˆÌ· Ó· ‰ËÌÔÛÈÂ‡ÂÈ ¿ÚıÚ· ÌÂ È‰È·›ÙÂÚÔ ÂÈÛÙËÌÔÓÈÎfi ÂÓ‰È·Ê¤ÚÔÓ, Î·ıÒ˜ Î·È ¿ÚıÚ· ÌÂ Â›Î·ÈÚ· ı¤Ì·Ù· ¯ˆÚ›˜ Ó· ÙËÚÂ›Ù·È Ë ÛÂÈÚ¿ ˘Ô‚ÔÏ‹˜. ∂›ÛË˜, ÌÔÚÂ› Ó· ·ÔÊ·Û›˙ÂÈ ÁÈ· ÙË ‰ËÌÔÛ›Â˘ÛË ÂÚÁ·ÛÈÒÓ Ô˘ ¤¯Ô˘Ó ·ÚÔ˘ÛÈ·ÛÙÂ› ÛÙÔ ÂÙ‹ÛÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ, ÙËÓ ÔÏÈÎ‹ ‹ ÌÂÚÈÎ‹ ‰ËÌÔÛ›Â˘ÛË ·ÚÔ˘ÛÈ¿ÛÂˆÓ È‰È·›ÙÂÚÔ˘ ÂÓ‰È·Ê¤ÚÔÓÙÔ˜ Î·È ÙËÓ ÔÏÈÎ‹ ‹ ÌÂÚÈÎ‹ ‰ËÌÔÛ›Â˘ÛË ÂÈÛÙÔÏÒÓ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÂ ‰ËÌÔÛÈÂ˘Ì¤Ó· ÂÈÛÙËÌÔÓÈÎ¿ ¿ÚıÚ· ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. ™ÙÈ˜ ÂÚÁ·Û›Â˜ ÌÂ Â›Î·ÈÚ· ı¤Ì·Ù· Ú¤ÂÈ Ó· ·Ó·ÁÚ¿ÊÂÙ·È ÛÙËÓ ÚÒÙË ÛÂÏ›‰· Ë ÚfiıÂÛË ÙˆÓ Û˘ÁÁÚ·Ê¤ˆÓ ÁÈ· ÙËÓ ·Ó·ÁÎ·ÈfiÙËÙ· ÙË˜ Ù·¯Â›·˜ ‰ËÌÔÛ›Â˘ÛË˜. ∏ ∂ÈÙÚÔ‹ ™‡ÓÙ·ÍË˜ ‰È·ÙËÚÂ› ÙÔ ‰ÈÎ·›ˆÌ· ÙË˜ ·Ô‰Ô¯‹˜ ÙË˜ Ù·¯Â›·˜ ‰ËÌÔÛ›Â˘ÛË˜. ŸÏÂ˜ ÔÈ ÂÚÁ·Û›Â˜ Ú¤ÂÈ Ó· ÌËÓ ¤¯Ô˘Ó ÂÓ Ì¤ÚÂÈ ‹ ÂÍ ÔÏÔÎÏ‹ÚÔ˘ ‰ËÌÔÛÈÂ˘ıÂ› ‹ ˘Ô‚ÏËıÂ› ÁÈ· ÎÚ›ÛË ÛÂ ¿ÏÏÔ ÂÚÈÔ‰ÈÎfi. ∂ÈÏ¤ÔÓ, ÛÙËÓ ÂÚÁ·Û›· ı· Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È Ù˘¯fiÓ ÂÈ‰ÔÙ‹ÛÂÈ˜-¯ÔÚËÁ›Â˜ ‹ ¿ÏÏÂ˜ ËÁ¤˜ ˘ÔÛÙ‹ÚÈÍË˜. ŸÏÂ˜ ÔÈ ÎÏÈÓÈÎ¤˜ ¤ÚÂ˘ÓÂ˜ Ú¤ÂÈ Ó· ¤¯Ô˘Ó Á›ÓÂÈ ÌÂÙ¿ ·fi ÏËÚÔÊÔÚËÌ¤ÓË Û˘Ó·›ÓÂÛË ÙˆÓ ÌÂÙÂ¯fiÓÙˆÓ ‹ ÙˆÓ ÓÔÌ›ÌˆÓ ÂÎÚÔÛÒˆÓ ÙÔ˘˜, Û‡ÌÊˆÓ· ÌÂ ÙÈ˜ ‰È·ÎËÚ‡ÍÂÈ˜ ÙÔ˘ EÏÛ›ÓÎÈ Î·È ÙÔ˘ TfiÎÈÔ. E›ÛË˜, Ú¤ÂÈ Ó· ¤¯Ô˘Ó ÙËÚËıÂ› ÔÈ Ô‰ËÁ›Â˜ ÁÈ· ÙË ÊÚÔÓÙ›‰· ÂÈÚ·Ì·Ùfi˙ˆˆÓ ÙÔ˘ ∂ıÓÈÎÔ‡ πÓÛÙÈÙÔ‡ÙÔ˘ ÀÁÂ›·˜ ÙˆÓ ∏¶∞ (DHEW Publication, NIH, 80-23). OÈ ÎÏÈÓÈÎ¤˜ ÌÂÏ¤ÙÂ˜ Ú¤ÂÈ Ó· ¤¯Ô˘Ó ÂÁÎÚÈıÂ› ·fi ÙËÓ ÂÈÙÚÔ‹ ∏ıÈÎ‹˜ Î·È ¢ÂÔÓÙÔÏÔÁ›·˜ ÙÔ˘ ¡ÔÛÔÎÔÌÂ›Ô˘. OÈ ·fi„ÂÈ˜ Î·È Ù· Û˘ÌÂÚ¿ÛÌ·Ù· ÙˆÓ Û˘ÁÁÚ·Ê¤ˆÓ Ô˘ ‰È·Ù˘ÒÓÔÓÙ·È ÛÙÈ˜ ‰ËÌÔÛÈÂ˘Ì¤ÓÂ˜ ÂÚÁ·Û›Â˜ ‰ÂÓ ·ÓÙÈÎ·ÙÔÙÚ›˙Ô˘Ó ··Ú·›ÙËÙ· ·˘Ù¤˜ ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. H Î·Ù·¯ÒÚÈÛË ‰È·ÊËÌ›ÛÂˆÓ ÛÙÔ ÂÚÈÔ‰ÈÎfi ‰ÂÓ ˘Ô‰ËÏÒÓÂÈ ÔˆÛ‰‹ÔÙÂ ¤ÁÎÚÈÛË ÙˆÓ ÂÚÈÂ¯ÔÌ¤ÓˆÓ ÙÔ˘˜ ·fi ÙËÓ EÏÏËÓÈÎ‹ ¶·È‰È·ÙÚÈÎ‹ EÙ·ÈÚÂ›·, ÙË ™˘ÓÙ·ÎÙÈÎ‹ EÈÙÚÔ‹ ‹ ·fi ÙÔÓ EÎ‰fiÙË ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. ŸÏÂ˜ ÔÈ ‰ËÌÔÛÈÂ˘Ì¤ÓÂ˜ ÂÚÁ·Û›Â˜ ıÂˆÚÔ‡ÓÙ·È È‰ÈÔÎÙËÛ›· ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡ “¶·È‰È·ÙÚÈÎ‹” Î·È Ë ÔÏÈÎ‹ ‹ ÌÂÚÈÎ‹

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·Ó·‰ËÌÔÛ›Â˘Û‹ ÙÔ˘˜ ÂÈÙÚ¤ÂÙ·È ÌﬁÓÔ ÌÂÙ¿ ·ﬁ ¤ÁÁÚ·ÊË Û˘ÁÎ·Ù¿ıÂÛË ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡.

µ. ™‡ÓÙ·ÍË ÙˆÓ ∂ÚÁ·ÛÈÒÓ ŸÏÂ˜ ÔÈ ÂÚÁ·Û›Â˜ Ú¤ÂÈ Ó· ·ÎÔÏÔ˘ıÔ‡Ó “∫ÔÈÓ¤˜ ¶ÚÔ‰È·ÁÚ·Ê¤˜ ÁÈ· ÃÂÈÚfiÁÚ·Ê· Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È ÛÂ µÈÔ˚·ÙÚÈÎ¿ ¶ÂÚÈÔ‰ÈÎ¿” (Uniform Requirements for Manuscripts Submitted to Biomedical Journals), ÔÈ ÔÔ›Â˜ ÙÚÔÔÔÈ‹ıËÎ·Ó ÚfiÛÊ·Ù· Î·È ‰ËÌÔÛÈÂ‡ÔÓÙ·È ÛÙÈ˜ ‰ÈÂ˘ı‡ÓÛÂÈ˜: http://www.icmje.org Î·È http://www.icmje.org/icmje.pdf TÔ Û‡ÓÔÏÔ ÙË˜ ÂÚÁ·Û›·˜ (Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙˆÓ ÈÓ¿ÎˆÓ Î·È ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ ÂÈÎfiÓˆÓ) Ú¤ÂÈ Ó· Â›Ó·È Ù˘ˆÌ¤ÓÔ ÛÙË ÌÈ· fi„Ë ÏÂ˘ÎÔ‡ ¯·ÚÙÈÔ‡ ÌÂÁ¤ıÔ˘˜ A4 (21x29,7 cm), ÌÂ ‰ÈÏfi ‰È¿ÛÙËÌ· ÌÂÙ·Í‡ ÙˆÓ ÁÚ·ÌÌÒÓ Î·È ÂÚÈıÒÚÈ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 2,5 cm ÛÙÈ˜ ‰‡Ô ÏÂ˘Ú¤˜. TÔ ÎÂ›ÌÂÓÔ Ú¤ÂÈ Ó· ¤¯ÂÈ ÙËÓ ·ÎfiÏÔ˘ıË ‰È¿Ù·ÍË: ÛÂÏ›‰· Ù›ÙÏÔ˘, ‚Ú·¯‡˜ Ù›ÙÏÔ˜, ÂÚ›ÏË„Ë ÛÙ· ÂÏÏËÓÈÎ¿ Î·È Ù· ·ÁÁÏÈÎ¿, Î·Ù¿ÏÔÁÔ˜ Û˘ÓÙÔÌÔÁÚ·ÊÈÒÓ, ÎÂ›ÌÂÓÔ, Â˘¯·ÚÈÛÙ›Â˜ Î·ıÒ˜ Î·È ·Ó·ÊÔÚ¿ ÛÂ ÂÈ‰ÔÙ‹ÛÂÈ˜-¯ÔÚËÁ›Â˜ ‹ ¿ÏÏÂ˜ ËÁ¤˜ ˘ÔÛÙ‹ÚÈÍË˜, ‚È‚ÏÈÔÁÚ·Ê›·, ›Ó·ÎÂ˜, ÂÈÎfiÓÂ˜, Ù›ÙÏÔÈ ÂÈÎfiÓˆÓ. K¿ıÂ ¤Ó· ·fi Ù· ·Ú·¿Óˆ ÛÙÔÈ¯Â›· Ú¤ÂÈ Ó· ·Ú¯›˙ÂÈ ÛÂ ¯ˆÚÈÛÙfi Ê‡ÏÏÔ Î·È ÔÈ ÛÂÏ›‰Â˜ Ó· ·ÚÈıÌÔ‡ÓÙ·È ‰È·‰Ô¯ÈÎ¿ ·Ú¯›˙ÔÓÙ·˜ ÌÂ ÙË ÛÂÏ›‰· Ù›ÙÏÔ˘. H ¤ÎÙ·ÛË ÚÔÛ‰ÈÔÚ›˙ÂÙ·È ÁÈ·: ñ ÙÈ˜ ·Ó·ÛÎÔ‹ÛÂÈ˜ ÛÂ 2000-3000 Ï¤ÍÂÈ˜. ñ ÙÈ˜ ÂÚÂ˘ÓËÙÈÎ¤˜ ÂÚÁ·Û›Â˜ ÛÂ 1500-2500 Ï¤ÍÂÈ˜ Î·È ÙÈ˜ ÂÓ‰È·Ê¤ÚÔ˘ÛÂ˜ ÂÚÈÙÒÛÂÈ˜ ÛÂ 1000-1500 Ï¤ÍÂÈ˜. ñ ÙÈ˜ ‚Ú·¯Â›Â˜ ‰ËÌÔÛÈÂ‡ÛÂÈ˜ ÛÂ 1000-1500 Ï¤ÍÂÈ˜. ñ ÙÈ˜ ÂÈÛÙÔÏ¤˜ ÛÂ 250-500 Ï¤ÍÂÈ˜.

™ÂÏ›‰· Ù›ÙÏÔ˘ ¶Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ: ñ ÙÔÓ Ù›ÙÏÔ (<14 Ï¤ÍÂÈ˜), Î·ıÒ˜ Î·È ÙÔÓ ‚Ú·¯‡ Ù›ÙÏÔ (<5 Ï¤ÍÂÈ˜) ÙÔ˘ ¿ÚıÚÔ˘. ¢ÂÓ ÂÈÙÚ¤ÔÓÙ·È Û˘ÓÙÌ‹ÛÂÈ˜. ñ ÙÔ fiÓÔÌ· Î·È ÙÔ ÂÒÓ˘ÌÔ Î¿ıÂ Û˘ÁÁÚ·Ê¤· ÛÙËÓ ÔÓÔÌ·ÛÙÈÎ‹. ñ ÙÔ ÂÈÛÙËÌÔÓÈÎfi Î¤ÓÙÚÔ (›‰Ú˘Ì·, ÎÏÈÓÈÎ‹, ÂÚÁ·ÛÙ‹ÚÈÔ) ·fi fiÔ˘ ÚÔ¤Ú¯ÂÙ·È Ë ÂÚÁ·Û›·. ™Â ÂÚ›ÙˆÛË ¤ÏÏÂÈ„Ë˜ Û˘ÓÂÚÁ·Û›·˜ ÌÂ Û˘ÁÎÂÎÚÈÌ¤Ó· Î¤ÓÙÚ·, Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÂÙ·È Ë È‰ÈfiÙËÙ· ÙÔ˘/ÙˆÓ Û˘ÁÁÚ·Ê¤·/ˆÓ (.¯. È‰ÈÒÙË˜ ·È‰›·ÙÚÔ˜) Î·È Ô ÙfiÔ˜ ‰È·ÌÔÓ‹˜ ÙÔ˘/ÙÔ˘˜. ñ ÙËÓ Ï‹ÚË ‰ÈÂ‡ı˘ÓÛË, e-mail Î·È ÙÔ ÙËÏ¤ÊˆÓÔ ÙÔ˘ Û˘ÁÁÚ·Ê¤· ÌÂ ÙÔÓ ÔÔ›Ô Á›ÓÂÙ·È Ë ·ÏÏËÏÔÁÚ·Ê›·.

¶ÂÚÈÏ‹„ÂÈ˜ H ÂÚ›ÏË„Ë Ú¤ÂÈ Ó· ·Ó·ÎÂÊ·Ï·ÈÒÓÂÈ ÙÔ˘˜ ÛÙfi¯Ô˘˜ ÙË˜ ÂÚÁ·Û›·˜, ÙË ÌÂıÔ‰ÔÏÔÁ›·, Ù· Î˘ÚÈfiÙÂÚ· ·ÔÙÂÏ¤ÛÌ·Ù· Î·È Ù· Û˘ÌÂÚ¿ÛÌ·Ù· ÙË˜ ÌÂÏ¤ÙË˜. ñ £· Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ˘Ï¿¯ÈÛÙÔÓ 200 Ï¤ÍÂÈ˜, fiÌˆ˜ ‰ÂÓ ı· Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙÈ˜ 250 Ï¤ÍÂÈ˜. ñ ∏ ÂÚ›ÏË„Ë ÙˆÓ ÂÚÁ·ÛÈÒÓ Ú¤ÂÈ Ó· Â›Ó·È ‰ÔÌËÌ¤ÓË ÛÙÈ˜ ÂÍ‹˜ ·Ú·ÁÚ¿ÊÔ˘˜: ÂÈÛ·ÁˆÁ‹, Ì¤ıÔ‰ÔÈ, ·ÔÙÂÏ¤ÛÌ·Ù· Î·È Û˘ÌÂÚ¿ÛÌ·Ù·. ™ÙËÓ ÂÚ›ÏË„Ë ÛÙ· ·ÁÁÏÈÎ¿ Ú¤ÂÈ Ó· ·Ó·ÁÚ¿ÊÔÓÙ·È ÛÙËÓ ·Ú¯‹ ÙÔ˘ ÎÂÈÌ¤ÓÔ˘ Ô Ù›ÙÏÔ˜ ÙË˜ ÂÚÁ·Û›·˜ Î·È Ù· ÔÓfiÌ·Ù· ÙˆÓ Û˘ÁÁÚ·Ê¤ˆÓ ÛÙ· ·ÁÁÏÈÎ¿. TÔ ÂÚÈÂ¯fiÌÂÓÔ ÙÔ˘ ·ÁÁÏÈÎÔ‡ ÎÂÈÌ¤ÓÔ˘ Ú¤ÂÈ Ó· Â›Ó·È ‰ÔÌËÌ¤ÓÔ ÛÂ: ÂÈÛ·ÁˆÁ‹ (background), Ì¤ıÔ‰ÔÈ (methods), ·ÔÙÂÏ¤ÛÌ·Ù· (results) Î·È Û˘ÌÂÚ¿ÛÌ·Ù· (conclusions). H ÂÚ›ÏË„Ë ÛÙ· ·ÁÁÏÈÎ¿ ‰ÂÓ Ú¤ÂÈ Ó· ‰È·Ê¤ÚÂÈ ·fi ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÛÙ· ÂÏÏËÓÈÎ¿.

xiv

K¿Ùˆ ·ﬁ ÙËÓ ÂÏÏËÓÈÎ‹ Î·È ÙËÓ ·ÁÁÏÈÎ‹ ÂÚ›ÏË„Ë ÛËÌÂÈÒÓÔÓÙ·È ÙÚÂÈ˜ ¤ˆ˜ ¤ÓÙÂ Ï¤ÍÂÈ˜ ÎÏÂÈ‰È¿ Ô˘ ı· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÁÈ· ÙÔ ıÂÌ·ÙÈÎﬁ Â˘ÚÂÙ‹ÚÈÔ.

KÂ›ÌÂÓÔ OÈ ÂÚÂ˘ÓËÙÈÎ¤˜ ÂÚÁ·Û›Â˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó: ÂÈÛ·ÁˆÁ‹, ÌÂıfi‰Ô˘˜, ·ÔÙÂÏ¤ÛÌ·Ù· Î·È Û˘˙‹ÙËÛË. H ÂÈÛ·ÁˆÁ‹ ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· ÙÂÏÂ˘Ù·›· ‰Â‰ÔÌ¤Ó· ÙË˜ ¤ÚÂ˘Ó·˜ ÛÙÔ Û˘ÁÎÂÎÚÈÌ¤ÓÔ ı¤Ì· ÌÂ ÙÈ˜ Î˘ÚÈfiÙÂÚÂ˜ ‚È‚ÏÈÔÁÚ·ÊÈÎ¤˜ ·Ú·ÔÌ¤˜ Î·È ÙÔÓ ÛÎÔfi ÙË˜ ÂÚÁ·Û›·˜. H ÂÚÈÁÚ·Ê‹ ÙˆÓ ÌÂıfi‰ˆÓ Ú¤ÂÈ Ó· Â›Ó·È ·ÎÚÈ‚‹˜ Î·È ·ÚÎÂÙ¿ ÏÂÙÔÌÂÚ‹˜, ÒÛÙÂ Ó· ÂÈÙÚ¤ÂÈ ÙËÓ ·Ó··Ú·ÁˆÁ‹ ÙÔ˘˜ ·fi ¿ÏÏÔ˘˜ ÂÚÂ˘ÓËÙ¤˜. ∂›ÛË˜, Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È ÌÂ ÏÂÙÔÌ¤ÚÂÈÂ˜ ÔÈ ÛÙ·ÙÈÛÙÈÎ¤˜ Ì¤ıÔ‰ÔÈ ·Ó¿Ï˘ÛË˜ Î·È ·ÍÈÔÏfiÁËÛË˜ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ. T· ·ÔÙÂÏ¤ÛÌ·Ù· Ú¤ÂÈ Ó· ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÌÂ Û·Ê‹ÓÂÈ· Î·È Ó· Û˘ÓÔ‰Â‡ÔÓÙ·È ·fi ÙËÓ ··Ú·›ÙËÙË ÛÙ·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË. H Û˘˙‹ÙËÛË Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· Û˘ÌÂÚ¿ÛÌ·Ù· Ô˘ ÚÔÎ‡ÙÔ˘Ó ·fi ÙËÓ ÂÚÁ·Û›·, ÙË ÛËÌ·Û›· Ô˘ ÌÔÚÂ› Ó· ¤¯Ô˘Ó Î·È ÙËÓ Èı·Ó‹ Û˘Û¯¤ÙÈÛ‹ ÙÔ˘˜ ÌÂ ·Ú·ÙËÚ‹ÛÂÈ˜ ¿ÏÏˆÓ ÂÚÂ˘ÓËÙÒÓ. OÈ ÂÓ‰È·Ê¤ÚÔ˘ÛÂ˜ ÂÚÈÙÒÛÂÈ˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Û‡ÓÙÔÌË ÂÈÛ·ÁˆÁ‹, ÂÚÈÁÚ·Ê‹ ÙË˜ ÂÚ›ÙˆÛË˜ Î·È ‚Ú·¯Â›· Û˘˙‹ÙËÛË, ÌÂ ¤ÌÊ·ÛË ÛÙË ‰È·ÊÔÚÈÎ‹ ‰È¿ÁÓˆÛË. T· ˘fiÏÔÈ· ı¤Ì·Ù· ¤¯Ô˘Ó ÂÏÂ‡ıÂÚË ‰ÔÌ‹ Î·Ù¿ ÙËÓ ÎÚ›ÛË ÙˆÓ Û˘ÁÁÚ·Ê¤ˆÓ ÙÔ˘˜. ∂˘¯·ÚÈÛÙ›Â˜ ‹ ·Ó·ÁÓˆÚ›ÛÂÈ˜ (·Ó·ÊÔÚ¿ ÛÂ ÂÈ‰ÔÙ‹ÛÂÈ˜-¯ÔÚËÁ›Â˜ ‹ ¿ÏÏÂ˜ ËÁ¤˜ ˘ÔÛÙ‹ÚÈÍË˜) ı· Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ Ù¤ÏÔ˜ ÙÔ˘ ÎÂÈÌ¤ÓÔ˘ Î·È ÚÈÓ ·fi ÙÈ˜ ‚È‚ÏÈÔÁÚ·ÊÈÎ¤˜ ·Ú·ÔÌ¤˜.

Editors/ Uniform Requirements for Manuscripts Sub-mitted to Biomedical Journals, (http://www.icmje.org Î·È http:// www.icmje.org/icmje.pdf). OÈ Û˘ÓÙÌ‹ÛÂÈ˜ ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ ÂÚÈÔ‰ÈÎÒÓ Á›ÓÔÓÙ·È ÌÂ ‚¿ÛË ÙÔ Cumulated Index Medicus [List of Journals Indexed in Index Medicus (http://www.nlm.nih.gov/bsd/uniform_requirements.html)]. ¶·Ú·‰Â›ÁÌ·Ù· ‚È‚ÏÈÔÁÚ·ÊÈÎÒÓ ·Ú·ÔÌÒÓ I. ¶∂ƒπO¢π∫∞ AÓ ÔÈ Û˘ÁÁÚ·ÊÂ›˜ Â›Ó·È ¤ˆ˜ ¤ÍÈ, ·Ó·ÁÚ¿ÊÔÓÙ·È fiÏÔÈ, ÂÓÒ ·Ó Â›Ó·È ÂÙ¿ ‹ ÂÚÈÛÛfiÙÂÚÔÈ, ·Ó·ÁÚ¿ÊÔÓÙ·È ÔÈ ÚÒÙÔÈ ¤ÍÈ Î·È ÚÔÛÙ›ıÂÙ·È “et al” ‹ “Î·È Û˘Ó”. T·ÎÙÈÎ‹ ¤Î‰ÔÛË ÂÚÈÔ‰ÈÎÔ‡: ∞ÓÙˆÓ›Ô˘ ¢, ª¿Ú· Ã, °È·ÓÓ¿ÙÔ˘ Ã. ∂Ì‚fiÏÈ·: Â›‰Ú·ÛË ÛÙËÓ ÂÈ‰ËÌÈÔÏÔÁ›· ÙˆÓ ÏÔÈÌˆ‰ÒÓ ÓÔÛËÌ¿ÙˆÓ Î·È ÙËÓ ·È‰È·ÙÚÈÎ‹ Ú¿ÍË. ¶·È‰È·ÙÚÈÎ‹ 1999;59:272-279. Proesmans W. Bartter syndrome and its neonatal variant. Eur J Pediatr 1997;156:669-679. ™˘ÌÏËÚˆÌ·ÙÈÎfi ÙÂ‡¯Ô˜ ÂÚÈÔ‰ÈÎÔ‡: Flyvbjerg A. Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in the renal complications of diabetes. Kidney Int 1997;52 (60 Suppl):S12-S19. ÃˆÚ›˜ Û˘ÁÁÚ·Ê¤·: National Institutes of Health Consensus Development Conference. Neurofibromatosis conference statement. Arch Neurol 1988;45:575-578.

TÈÌ¤˜ ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛÂˆÓ OÈ ÙÈÌ¤˜ ÙˆÓ ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛÂˆÓ Ú¤ÂÈ Ó· ÂÎÊÚ¿˙ÔÓÙ·È ÛÙÔ ¢ÈÂıÓ¤˜ ™‡ÛÙËÌ· MÔÓ¿‰ˆÓ (SI Units) Î·È ÛÙÔ MÂÙÚÈÎﬁ (Conventional-™˘Ì‚·ÙÈÎﬁ) ™‡ÛÙËÌ· Ì¤Û· ÛÂ ·Ú¤ÓıÂÛË. ¶›Ó·ÎÂ˜ ÌÂÙ·ÙÚÔ‹˜ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙÈ˜ ‰ÈÂ˘ı‡ÓÛÂÈ˜: http://www.icmje.org Î·È http://www.icmje.org/icmje.pdf

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ OÈ Û˘ÓÙÔÌÔÁÚ·Ê›Â˜ Ô˘ ¤¯Ô˘Ó ÂÈ‚ÏËıÂ› ‰ÈÂıÓÒ˜, ‰ËÌÔÛÈÂ‡ÔÓÙ·È ÛÂ Î¿ıÂ ÙÂ‡¯Ô˜ ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. ™‡ÓıÂÙÔÈ Î·È Ì·ÎÚÔÛÎÂÏÂ›˜ fiÚÔÈ Ô˘ Â·Ó·Ï·Ì‚¿ÓÔÓÙ·È Û˘¯Ó¿ ÛÙÔ ÎÂ›ÌÂÓÔ ÌÔÚÔ‡Ó Ó· ·ÓÙÈÎ·ı›ÛÙ·ÓÙ·È ·fi Û˘ÓÙÔÌÔÁÚ·Ê›Â˜ Ô˘ ÂÂÍËÁÔ‡ÓÙ·È ·fi ÙÔ˘˜ Û˘ÁÁÚ·ÊÂ›˜ ÛÂ ÂÈ‰ÈÎfi Î·Ù¿ÏÔÁÔ, Ô ÔÔ›Ô˜ ˘Ô‚¿ÏÏÂÙ·È Ì·˙› ÌÂ ÙËÓ ÂÚÁ·Û›·. OÈ Û˘ÓÙÔÌÔÁÚ·Ê›Â˜ ·Ó·Ê¤ÚÔÓÙ·È ÛÂ ·Ú¤ÓıÂÛË ÌfiÓÔ ÛÙÈ˜ ÂÚÈÏ‹„ÂÈ˜.

BÈ‚ÏÈÔÁÚ·ÊÈÎ¤˜ ·Ú·ÔÌ¤˜ ™ÙÔ ÙÌ‹Ì· ÙË˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ Î·Ù·¯ˆÚÔ‡ÓÙ·È ﬁÏÂ˜ ÔÈ ‚È‚ÏÈÔÁÚ·ÊÈÎ¤˜ ·Ú·ÔÌ¤˜ ÌÂ ÙË ÛÂÈÚ¿ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ ÎÂ›ÌÂÓÔ. ™ÙÔ ÎÂ›ÌÂÓÔ, ÔÈ ‚È‚ÏÈÔÁÚ·ÊÈÎ¤˜ ·Ú·ÔÌ¤˜ ·Ó·Ê¤ÚÔÓÙ·È ÌÂ ·Ú·‚ÈÎÔ‡˜ ·ÚÈıÌÔ‡˜ ÛÂ ·Ú¤ÓıÂÛË. OÈ ‚È‚ÏÈÔÁÚ·ÊÈÎ¤˜ ·Ú·ÔÌ¤˜ ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÔ˘Ó:

¶ÚÔÛ‰ÈÔÚÈÛÌﬁ˜ Ù‡Ô˘ ¿ÚıÚÔ˘: Schreiner GF, Lange L. Ethanol modulation of macrophage influx in glomerulonephritis [Abstract]. J Am Soc Nephrol 1991;2:562. Should antileukotriene therapies be used instead of inhaled corticosteroids in asthma? [Editorial]. Am J Respir Crit Care Med 1998;158:1697-1701. Laux-End R, Inaebnit D, Gerber HA, Bianchetti MG. Vasculitis associated with levamisole and circulating autoantibodies [Letter]. Arch Dis Child 1996;75:355-356. II. µπµ§π∞ ∫ÂÊ¿Ï·ÈÔ ÛÂ ‚È‚Ï›Ô: Clark AG, Barratt TM. Steroid-responsive nephrotic syndrome. In: Barratt TM, Arner ED, Harmon WE, editors. Pediatric Nephrology. 4th ed. Baltimore: Lippincott William Wilkins; 1999. p. 742. ™‡ÁÁÚ·ÌÌ· ‹ ÌÔÓÔÁÚ·Ê›·: Gorlin RJ, Cohen MM, Levin LS. Syndromes of the head and neck. 3rd ed. New York: Oxford University Press; 1990.

ñ ÙÈ˜ 70 ÛÙÈ˜ ·Ó·ÛÎÔ‹ÛÂÈ˜. ñ ÙÈ˜ 30 ÛÙÈ˜ ÂÚÂ˘ÓËÙÈÎ¤˜ ÂÚÁ·Û›Â˜. ñ ÙÈ˜ 12 ÛÙ· Â›Î·ÈÚ· ı¤Ì·Ù· Î·È ÙÈ˜ ÂÓ‰È·Ê¤ÚÔ˘ÛÂ˜ ÂÚÈÙÒÛÂÈ˜. ñ ÙÈ˜ 5 ÛÙÈ˜ ‚Ú·¯Â›Â˜ ‰ËÌÔÛÈÂ‡ÛÂÈ˜ Î·È ÙÈ˜ ÂÈÛÙÔÏ¤˜.

¢ËÌÔÛ›Â˘ÛË ÛÂ ÙﬁÌÔ Ú·ÎÙÈÎÒÓ: Bauer AW. The two definitions of bacterial resistance. In: Smith AJ, Rogers CA, eds. Proceedings of the Third International Congress of Chemotherapy; 1962 May 29-31; New York: International Society of Chemotherapy; 1963. p. 484-500.

H Û‡ÓÙ·ÍË ÙˆÓ ‚È‚ÏÈÔÁÚ·ÊÈÎÒÓ ·Ú·ÔÌÒÓ Á›ÓÂÙ·È Û‡ÌÊˆÓ· ÌÂ ÙÈ˜ ÚﬁÛÊ·Ù· ÙÚÔÔÔÈËÌ¤ÓÂ˜ ÚÔ‰È·ÁÚ·Ê¤˜ ÙË˜ International Committee of Medical Journal

¢È‰·ÎÙÔÚÈÎ‹ ‰È·ÙÚÈ‚‹: ¶··‰ﬁÔ˘ÏÔ˜ Ã. ∏ ıÂÚ·Â›· ÙÔ˘ ÛÙÚ·‚ÈÛÌÔ‡ [‰È‰·ÎÙÔÚÈÎ‹ ‰È·ÙÚÈ‚‹]. ∞ı‹Ó·: ¶·ÓÂÈÛÙ‹ÌÈÔ ∞ıËÓÒÓ; 1979.

Kaplan SJ. Post hospital home health care: the elderly’s access and utilization [dissertation]. St. Louis (Mo): Washington Univ.; 1995. πππ. CD-ROM Anderson SC, Poulsen KB. Anderson’s electronic atlas of hematology [CD-ROM]. Philadelphia: Lippincott Williams & Wilkins; 2002. IV. ™∆O ¢π∞¢π∫∆ÀO ÕÚıÚÔ ÛÂ ÂÚÈÔ‰ÈÎﬁ: Abood S. Quality improvement initiative in nursing homes: the ANA acts in an advisory role. Am J Nurs [Internet]. 2002 Jun: Webpage: http://www.nursingworld.org/AJN/2002/june/Wawatch.htm ªÔÓÔÁÚ·Ê›·: Foley KM, Gelband H, editors. Improving palliative care for cancer [Monograph, Internet]. Washington: National Academy Press; 2001. Webpage: http://www.nap.edu/books/0309074029/html

¶›Ó·ÎÂ˜ Î·È EÈÎfiÓÂ˜ AÔÛÙ¤ÏÏÔÓÙ·È ÂÈ˜ ÙÚÈÏÔ‡Ó (¤Ó· ÚˆÙfiÙ˘Ô Î·È ‰‡Ô ÊˆÙÔ·ÓÙ›ÁÚ·Ê·). ¶Ú¤ÂÈ Ó· ¤¯Ô˘Ó Ï¿ÙÔ˜ ›ÛÔ ÌÂ ÙÔ Ï¿ÙÔ˜ ÙÔ˘ ÌÔÓfiÛÙËÏÔ˘ (7,5 cm) ‹ ÌÂ ÙÔ Ï¿ÙÔ˜ fiÏË˜ ÙË˜ ÛÂÏ›‰·˜ (15,5 cm). TÔ Ì¤ÁÈÛÙÔ Ì‹ÎÔ˜ ÙÔ˘˜, Ì·˙› ÌÂ ÙÔ˘˜ Ù›ÙÏÔ˘˜, ‰ÂÓ Ú¤ÂÈ Ó· Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ ·fi 22 cm. OÈ ›Ó·ÎÂ˜ ·ÚÈıÌÔ‡ÓÙ·È ÌÂ ·Ú·‚ÈÎÔ‡˜ ·ÚÈıÌÔ‡˜ ÌÂ ÙË ÛÂÈÚ¿ Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ ÎÂ›ÌÂÓÔ. ¶ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ‚Ú·¯‡ Ù›ÙÏÔ Î·È ÂÂÍ‹ÁËÛË ÙˆÓ Û˘ÓÙÌ‹ÛÂˆÓ ÛÙÔ Î¿Ùˆ Ì¤ÚÔ˜. ™ÙÔ˘˜ ›Ó·ÎÂ˜ Ú¤ÂÈ Ó· ·ÔÊÂ‡ÁÔÓÙ·È ÔÈ Î¿ıÂÙÂ˜ ÁÚ·ÌÌ¤˜. ŸÏÔ ÙÔ ·ÂÈÎÔÓÈÛÙÈÎfi ˘ÏÈÎfi (Û¯‹Ì·Ù·, ‰È·ÁÚ¿ÌÌ·Ù·, ÊˆÙÔÁÚ·Ê›Â˜, Î.Ï.) ¯·Ú·ÎÙËÚ›˙ÂÙ·È ˆ˜ ÂÈÎfiÓÂ˜ Î·È ı· Ú¤ÂÈ Ó· Â›Ó·È ¿ÚÈÛÙË˜ ÔÈfiÙËÙ·˜. ™ÙÔ ›Ûˆ Ì¤ÚÔ˜ ÙˆÓ ÂÈÎfiÓˆÓ Ú¤ÂÈ Ó· ÛËÌÂÈÒÓÂÙ·È ÌÂ ÌÔÏ‡‚È Ô ·ÚÈıÌfi˜ ÙË˜ ÂÈÎfiÓ·˜ Î·È ÙÔ fiÓÔÌ· ÙÔ˘ ÚÒÙÔ˘ Û˘ÁÁÚ·Ê¤·, Î·ıÒ˜ Î·È ¤Ó· ‚¤ÏÔ˜ ÙÔ ÔÔ›Ô Ó· ‰Â›¯ÓÂÈ ÙÔ ¿Óˆ Ì¤ÚÔ˜ ÙË˜ ÂÈÎfiÓ·˜. ™ÙÈ˜ ÊˆÙÔÁÚ·Ê›Â˜ ·ÛıÂÓÒÓ ‰ÂÓ Ú¤ÂÈ Ó· ·Ó·ÁÓˆÚ›˙ÂÙ·È Ë Ù·˘ÙfiÙËÙ¿ ÙÔ˘˜. OÈ ·ÛıÂÓÂ›˜ ‰ÂÓ Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È ÔÓÔÌ·ÛÙÈÎ¿.

πÛÙÔÛÂÏ›‰Â˜: Cancer-Pain.org [Webpage, Internet]. New York: Association of Cancer Online Resources, Inc.; 2002: http://www.cancer-pain.org/

°. ÀÔ‚ÔÏ‹ Î·È ¢ËÌÔÛ›Â˘ÛË ÙˆÓ ∂ÚÁ·ÛÈÒÓ ŸÏÂ˜ ÔÈ ÂÚÁ·Û›Â˜ Ú¤ÂÈ Ó· ˘Ô‚¿ÏÏÔÓÙ·È ÂÈ˜ ÙÚÈÏÔ‡Ó Î·È Ó· Û˘ÓÔ‰Â‡ÔÓÙ·È ·fi ‰ÈÛÎ¤Ù· ‹ CD, Î·ıÒ˜ Î·È ·fi ÂÈÛÙÔÏ‹, Ë ÔÔ›· ı· Û˘Ó˘ÔÁÚ¿ÊÂÙ·È ·fi fiÏÔ˘˜ ÙÔ˘˜ Û˘ÁÁÚ·ÊÂ›˜, ÛÙËÓ ÔÔ›· ı· ‰ËÏÒÓÂÙ·È fiÙÈ Ë ÂÚÁ·Û›· ‰ÂÓ ¤¯ÂÈ ÂÓ Ì¤ÚÂÈ ‹ ÂÍ ÔÏÔÎÏ‹ÚÔ˘ ‰ËÌÔÛÈÂ˘ıÂ› ‹ ˘Ô‚ÏËıÂ› ÁÈ· ÎÚ›ÛË ÛÂ ¿ÏÏÔ ÂÚÈÔ‰ÈÎfi Î·È fiÙÈ ÔÈ Û˘ÁÁÚ·ÊÂ›˜ ÂÁÎÚ›ÓÔ˘Ó ÙË ‰ËÌÔÛ›Â˘Û‹ ÙË˜ ÛÙÔ ÂÚÈÔ‰ÈÎfi “¶·È‰È·ÙÚÈÎ‹”. ∂ÈÏ¤ÔÓ, ı· Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È Ù˘¯fiÓ ÂÈ‰ÔÙ‹ÛÂÈ˜-¯ÔÚËÁ›Â˜ ‹ ¿ÏÏÂ˜ ËÁ¤˜ ˘ÔÛÙ‹ÚÈÍË˜. EÊfiÛÔÓ Ë ÂÚÁ·Û›· Á›ÓÂÈ ·Ô‰ÂÎÙ‹, ÙÔ ‰ÈÔÚıˆÌ¤ÓÔ Û‡ÌÊˆÓ· ÌÂ ÙÈ˜ ˘Ô‰Â›ÍÂÈ˜ ÙˆÓ ÎÚÈÙÒÓ Î·È ÂÎ Ó¤Ô˘ ‰·ÎÙ˘ÏÔÁÚ·ÊËÌ¤ÓÔ ÎÂ›ÌÂÓÔ Ú¤ÂÈ Ó· ˘Ô‚¿ÏÂÙ·È ÛÙË ™˘ÓÙ·ÎÙÈÎ‹ EÈÙÚÔ‹, Û˘ÓÔ‰Â˘fiÌÂÓÔ ·fi ‰ÈÛÎ¤Ù· ‹ CD Ô˘ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ ÂÚÁ·Û›· ÛÂ ÚfiÁÚ·ÌÌ· Word, Î·ıÒ˜ Î·È ÂÈÛÙÔÏ‹ fiÔ˘ Ó· ·Ó·Ê¤ÚÔÓÙ·È ·Ó·Ï˘ÙÈÎ¿ ÔÈ ÙÚÔÔÔÈ‹ÛÂÈ˜ ‹ ÔÈ ·ÓÙÈÚÚ‹ÛÂÈ˜ ÛÙÈ˜ ÚÔÙ¿ÛÂÈ˜ ÙˆÓ ÎÚÈÙÒÓ. H Î·ı˘ÛÙ¤ÚËÛË ÙË˜ Â·Ó˘Ô‚ÔÏ‹˜ ÙÔ˘ ÙÚÔÔÔÈËÌ¤ÓÔ˘ ÎÂÈÌ¤ÓÔ˘ ¤Ú·Ó ÙˆÓ 30 ËÌÂÚÒÓ Û˘ÓÂ¿ÁÂÙ·È Ó¤· ˘Ô‚ÔÏ‹. T· ¤ÍÔ‰· ÙˆÓ ÊÈÏÌ Î·È ÙˆÓ ·Ó·Ù‡ˆÓ ‚·Ú‡ÓÔ˘Ó ÙÔ˘˜ Û˘ÁÁÚ·ÊÂ›˜ Î·È Ú¤ÂÈ Ó· ÏËÚÒÓÔÓÙ·È ÌÂ ÙËÓ ·ÔÛÙÔÏ‹ ÙÔ˘ ÚÒÙÔ˘ ‰ÔÎÈÌ›Ô˘ Î·ÙÂ˘ıÂ›·Ó ÛÙÔÓ Ù˘ÔÁÚ¿ÊÔ. T· ÎÂ›ÌÂÓ· ÙˆÓ ÂÚÁ·ÛÈÒÓ Ô˘ ‰ÂÓ Á›ÓÔÓÙ·È ·Ô‰ÂÎÙ¤˜ ÁÈ· ‰ËÌÔÛ›Â˘ÛË, ‰ÂÓ ÂÈÛÙÚ¤ÊÔÓÙ·È. MÔÚÂ› Ó· ÂÈÛÙÚ·ÊÔ‡Ó, ÂÊfiÛÔÓ ˙ËÙËıÂ› ÂÓÙfi˜ ÂÍ·Ì‹ÓÔ˘, Ù· Û¯‹Ì·Ù· Î·È ÔÈ ÊˆÙÔÁÚ·Ê›Â˜ Ô˘ Ù· Û˘ÓÔ‰Â‡Ô˘Ó. OÈ ÂÚÁ·Û›Â˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È ÚÔ˜ ÎÚ›ÛË ÁÈ· ‰ËÌÔÛ›Â˘ÛË ÛÙÔ ÂÚÈÔ‰ÈÎfi “¶·È‰È·ÙÚÈÎ‹” ·ÔÛÙ¤ÏÏÔÓÙ·È ÂÈ˜ ÙÚÈÏÔ‡Ó ÛÙË ‰ÈÂ‡ı˘ÓÛË: ™˘ÓÙ·ÎÙÈÎ‹ EÈÙÚÔ‹, EÏÏËÓÈÎ‹ ¶·È‰È·ÙÚÈÎ‹ EÙ·ÈÚÂ›· MÈ¯·Ï·ÎÔÔ‡ÏÔ˘ 92, 115 28 Aı‹Ó·

¶ÚÈÓ ·ÔÛÙÂ›ÏÂÙÂ ÙËÓ ÂÚÁ·Û›· Û·˜, ‚Â‚·ÈˆıÂ›ÙÂ fiÙÈ ÂÚÈÏ·Ì‚¿ÓÂÈ: 1. 3 ·ÓÙ›ÁÚ·Ê· ÙÔ˘ ÎÂÈÌ¤ÓÔ˘ ÙË˜ ÂÚÁ·Û›·˜, Ù˘ˆÌ¤Ó· Û‡ÌÊˆÓ· ÌÂ ÙÈ˜ Ô‰ËÁ›Â˜. 2. ¢ÈÛÎ¤Ù· ‹ CD ÌÂ fiÏÔ ÙÔ ˘ÏÈÎfi ÙË˜ ÂÚÁ·Û›·˜ (ÎÂ›ÌÂÓÔ, ›Ó·ÎÂ˜, ÂÈÎfiÓÂ˜). 3. ∂ÈÛÙÔÏ‹ ˘Ô‚ÔÏ‹˜ Î·È ‰‹ÏˆÛË ÌË ÚÔÁÂÓ¤ÛÙÂÚË˜ ‰ËÌÔÛ›Â˘ÛË˜ ÙË˜ ÂÚÁ·Û›·˜. 4. ™ÂÏ›‰· Ù›ÙÏÔ˘ (¯ˆÚÈÛÙ‹ ÛÂÏ›‰·) ÂÚÈÏ·Ì‚¿ÓÂÈ: ·.Ù›ÙÏÔ Î·È ‚Ú·¯‡ Ù›ÙÏÔ ÂÚÁ·Û›·˜ ‚.fiÓÔÌ· Î·È ÂÒÓ˘ÌÔ Û˘ÁÁÚ·Ê¤ˆÓ (ÔÏÔÁÚ¿Êˆ˜) Á. ÂÈÛÙËÌÔÓÈÎfi/¿ Î¤ÓÙÚÔ/· fiÔ˘ ¤ÁÈÓÂ Ë ÂÚÁ·Û›· ‰.fiÓÔÌ·, ‰ÈÂ‡ı˘ÓÛË Î·È ÙËÏ¤ÊˆÓÔ Û˘ÁÁÚ·Ê¤· ÁÈ· ·ÏÏËÏÔÁÚ·Ê›·. 5. ¶ÂÚ›ÏË„Ë ÂÏÏËÓÈÎ‹-·ÁÁÏÈÎ‹, ‰ÔÌËÌ¤ÓË ÛÙÈ˜ ÂÍ‹˜ ·Ú·ÁÚ¿ÊÔ˘˜: ÂÈÛ·ÁˆÁ‹, Ì¤ıÔ‰ÔÈ, ·ÔÙÂÏ¤ÛÌ·Ù· Î·È Û˘ÌÂÚ¿ÛÌ·Ù·, Î·ıÒ˜ Î·È Ï¤ÍÂÈ˜ ÎÏÂÈ‰È¿ (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·). 6. ∫·Ù¿ÏÔÁÔ Û˘ÓÙÔÌÔÁÚ·ÊÈÒÓ (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·). 7. ∫Â›ÌÂÓÔ (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·). 8. ∂˘¯·ÚÈÛÙ›Â˜ ‹ ·Ó·ÁÓˆÚ›ÛÂÈ˜ (·Ó·ÊÔÚ¿ ÛÂ ÂÈ‰ÔÙ‹ÛÂÈ˜-¯ÔÚËÁ›Â˜ ‹ ¿ÏÏÂ˜ ËÁ¤˜ ˘ÔÛÙ‹ÚÈÍË˜). 9. µÈ‚ÏÈÔÁÚ·Ê›· (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·). 10. ¶›Ó·ÎÂ˜ (Ô Î·ı¤Ó·˜ ÛÂ ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·) ÂÈ˜ ÙÚÈÏÔ‡Ó. 11. ∂ÈÎfiÓÂ˜, ÌÂ ‚¤ÏÔ˜ ÛÙÔ ›Ûˆ Ì¤ÚÔ˜ ÙÔ ÔÔ›Ô Ó· ‰Â›¯ÓÂÈ ÚÔ˜ Ù· Â¿Óˆ, ·ÚÈıÌËÌ¤ÓÂ˜, ÂÈ˜ ÙÚÈÏÔ‡Ó. 12. ∆›ÙÏÔ˘˜ ÂÈÎfiÓˆÓ (‰ÈÏfi ‰È¿ÛÙËÌ· - Ô Î·ı¤Ó·˜ ÛÂ ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·) ÂÈ˜ ÙÚÈÏÔ‡Ó.

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™À¡∆√ª√°ƒ∞ºπ∂™ o

A cal cm cm2 cm3 o C g h IU kg l m mg min mm mol n NS ‹ ª™ osm p SD SE sec U

ABBREVIATIONS

angstrom ıÂÚÌ›‰· ÂÎ·ÙÔÛÙfi ÙÂÙÚ·ÁˆÓÈÎfi ÂÎ·ÙÔÛÙfi Î˘‚ÈÎfi ÂÎ·ÙÔÛÙfi ‚·ıÌfi˜ ∫ÂÏÛ›Ô˘ ÁÚ·ÌÌ¿ÚÈÔ ÒÚ· ‰ÈÂıÓ‹˜ ÌÔÓ¿‰· ¯ÈÏÈfiÁÚ·ÌÌÔ Ï›ÙÚÔ Ì¤ÙÚÔ ¯ÈÏÈfiÁÚ·ÌÌÔ ÏÂÙfi ¯ÈÏÈÔÛÙfiÌÂÙÚÔ ÁÚ·ÌÌÔÌfiÚÈÔ ·ÚÈıÌfi˜ ÌË ÛËÌ·ÓÙÈÎfi ÔÛÌÒÏÈÔ Èı·ÓfiÙËÙ· ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË ÛÙ·ıÂÚfi ÛÊ¿ÏÌ· ‰Â˘ÙÂÚfiÏÂÙÔ ÌÔÓ¿‰·

™˘Ó‰˘·˙ﬁÌÂÓ· ÚÔı¤Ì·Ù·

Combining prefixes

tera- (1012) giga- (109) mega- (106) kilo- (103) hector- (102) deca- (101) deci- (10-1) centi- (10-2) milli- (10-3) micro- (10-6) nano- (10-9) pico- (10-12) femto- (10-15) atto- (10-18)

T G M k h da d c m Ì n p f a

angstrom calorie centimeter square centimeter cubic centimeter degree Celsius gram hour international unit kilogram liter meter milligram minute millimeter mole number not significant osmole probability standard deviation standard error second unit

INSTRUCTIONS TO AUTHORS A. General Information The Greek Paediatric Society is the owner of “Paediatriki”, its official scientific journal, which is distributed to its members. Its objectives are the publication of paediatric scientific work and the continuing education of paediatricians. For this purpose, it publishes a variety of articles, and in particular: 1. Editorials (upon invitation by the Editorial Board). 2. Review articles. 3. Award-winning articles. 4. Original articles. 5. Clinical Quiz. 6. Round tables. 7. Current issues. 8. Issues of healthcare management and education. 9. Case reports. 10. News. 11. Brief reports. 12. Letters to the editor. 13. Abstracts. 14. Future congresses and events. 15. Book reviews. The Editorial Board reserves the right to publish articles of special scientific interest and articles on current issues without observing submission order. In addition it publishes upon decision original papers presented at the Annual Paediatric Conference, presentations of special interest - in whole or in part, and letters - in whole or in part - referring to scientific articles published in the journal. Regarding papers on current issues, the author’s request for immediate publication should be quoted on the first page. The Editorial Board reserves the right to accept such papers for immediate publication. All manuscripts should not have been published previously, in whole or in part, and not be under consideration by another publication. Manuscripts should acknowledge any funding, sponsorship or other financial support. All clinical research should have been conducted following informed consent of participants or of their legal representatives according to the Declarations of Helsinki and Tokyo. In addition, the US National Institute of Health guide for the care and use of laboratory animals (DHEW Publication, NIH, 80-23) should have been observed. Clinical trials should have been approved by the Ethics Committee of the Hospital. Authors’ opinions and conclusions expressed in the published papers do not necessarily reflect those of the journal. The Greek Paediatric Society, the Editorial Board and the Publisher of the journal do not necessarily approve the content of the advertisements appearing in the journal. The copyright of all published papers is held by “Paediatriki” and their reproduction in whole or in part is authorized only following written consent of the journal.

B. Manuscript Preparation “Paediatriki” suggests compliance with the “Uniform Requirements for Manuscripts Submitted to Biomedical Journals”, recently modified and published on the websites: http://www.icmje.org and http://www.icmje.org/icmje.pdf The entire paper (including figure legends and tables)

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should be typed on one side of blank paper format A4 (21x29.7 cm), double line spacing and minimum indent 2.5 cm on both sides. The paper should have the following structure: title page, short title, abstract in Greek and English, list of abbreviations, text, acknowledgements and quoting of grants, sponsorships or other financial support sources, references, tables, figures, figure legends. Each of these sections should be started on a new page. Pages should be numbered consecutively, beginning with the title page. Text length shall be: ñ review articles 2000-3000 words; ñ original articles 1500-2500 words and case reports 1000-1500 words; ñ brief reports 1000-1500 words; ñ letters 250-500 words. The title page should include: ñ the title (<14 words) and the short title (<5 words) of the article. No abbreviations are permitted in the title; ñ the name and surname of all authors; ñ the centre (institution, clinic, laboratory) of origin of the paper. If there is no affiliation with a specific centre, the status of the author(s) should be cited (e.g., private paediatrician) and home address; ñ the complete address, e-mail and telephone number of the author to whom correspondence should be addressed. Abstracts The abstract should summarize the objectives, methodology, main results and conclusions of the study. ñ It should contain at least 200 words, and not exceed 250 words. ñ It should consist of the following paragraphs: background, methods, results and conclusions. The English abstract should cite at the beginning the title of the paper and the authors’ names in English. The content of the text should consist of the following paragraphs: background, methods, results and conclusions. The abstract in English should not differ in content from the corresponding Greek abstract. Beneath the Greek and English abstracts, three to five key words in the respective language should be supplied, to be used in the thematic index. Text Original articles include: introduction, methods, results and discussion. The introduction includes the latest research data on the subject and the main references and the objectives of the paper. The description of the methods should be precise and detailed so as to enable reproduction by other researchers. In addition, the statistical methods of analysis and evaluation of the results should be described. Results should be presented clearly, together with the appropriate statistical analysis. Discussion should cover the results ensuing from the research, their significance and possible associations with the observations of other researchers. Case reports comprise a short introduction, case description and brief discussion, with emphasis on differential diagnosis. The structure of all other articles is free, according to the judgment of the authors. Thanks or acknowledgements (reference to grants, sponsorships or other sources of financial support) should be quoted at the end of the text, before references.

Units of measures of laboratory analyses Laboratory analyses should be expressed in the Système International (SI) units and in the metric (Conventional) system in parentheses. See conversion tables on the websites: http://www.icmje.org and http://www.icmje.org/icmje.pdf

II. BOOKS Chapter in book: Clark AG, Barratt TM. Steroid-responsive nephrotic syndrome. In: Barratt TM, Arner ED, Harmon WE, editors. Pediatric Nephrology. 4th ed. Baltimore: Lippincott William Wilkins; 1999. p. 742.

Abbreviations All issues of the journal contain internationally established abbreviations. Complex or long terms often repeated in the text may be replaced by abbreviations explained by the authors in a list submitted with the paper. Abbreviations are reported in parentheses only in abstracts.

Book or monograph: Gorlin RJ, Cohen MM, Levin LS. Syndromes of the head and neck. 3rd ed. New York: Oxford University Press; 1990.

References The reference section contains all references numbered in the order in which they appear in the text. In the text, references are to be indicated by Arabic numerals in parentheses. References should be no more than: ñ 70 in review articles; ñ 30 in original articles; ñ 12 in current issues and case reports; ñ 5 in brief reports and letters. In listing references follow the recently modified standards of the International Committee of Medical Journal Editors/Uniform Requirements for Manuscripts Submitted to Biomedical Journals, (http://www.icmje.org and http:// www.icmje.org/icmje.pdf). Abbreviated names of journals should conform to the Cumulated Index Medicus [List of Journals Indexed in Index Medicus (http://www.nlm.nih.gov/bsd/uniform_requirements.html)]. Examples of reference style I. JOURNALS All authors are cited if they are six or less; if they are 7 or more, the first six are cited, followed by “et al”. Regular edition: Proesmans W. Bartter syndrome and its neonatal variant. Eur J Pediatr 1997;156:669-679. Supplement issue: Flyvbjerg A. Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in the renal complications of diabetes. Kidney Int 1997;52 (60 Suppl):S12-S19. No author: National Institutes of Health Consensus Development Conference. Neurofibromatosis conference statement. Arch Neurol 1988;45:575-578. Article type specification: Schreiner GF, Lange L. Ethanol modulation of macrophage influx in glomerulonephritis [Abstract]. J Am Soc Nephrol 1991;2:562. Should antileukotriene therapies be used instead of inhaled corticosteroids in asthma? [Editorial]. Am J Respir Crit Care Med 1998;158:1697-1701. Laux-End R, Inaebnit D, Gerber HA, Bianchetti MG. Vasculitis associated with levamisole and circulating autoantibodies [Letter]. Arch Dis Child 1996;75:355-356.

Publication in a volume of proceedings: Bauer AW. The two definitions of bacterial resistance. In: Smith AJ, Rogers CA, eds. Proceedings of the Third International Congress of Chemotherapy; 1962 May 29-31; New York: International Society of Chemotherapy; 1963. p. 484-500. Doctoral dissertation: Kaplan SJ. Post hospital home health care: the elderly’s access and utilization [dissertation]. St. Louis (Mo): Washington Univ.; 1995. πππ. CD-ROM Anderson SC, Poulsen KB. Anderson’s electronic atlas of hematology [CD-ROM]. Philadelphia: Lippincott Williams & Wilkins; 2002. IV. ON THE INTERNET Article in journal Abood S. Quality improvement initiative in nursing homes: the ANA acts in an advisory role. Am J Nurs [Internet]. 2002 Jun: Webpage: http://www.nursingworld.org/ AJN/2002/june/Wawatch.htm Monograph Foley KM, Gelband H, editors. Improving palliative care for cancer [Monograph, Internet]. Washington: National Academy Press; 2001. Webpage: http://www.nap.edu/books/0309074029/html Websites Cancer-Pain.org [Webpage, Internet]. New York: Association of Cancer Online Resources, Inc.; 2002: http://www.cancer-pain.org/ Tables and Figures Three copies should be submitted (original plus 2 copies). Their width should either be equal to the width of one column (7.5 cm) or to the width of the page (15.5 cm). Their maximum length, titles included, should not exceed 22 cm. Tables are numbered with Arabic numerals in the order in which they appear in the text. They should have a short title and abbreviations should be listed at the bottom. Vertical lines in tables should be avoided. All illustration material is considered as figures (graphs, pictures, etc.). They should be of excellent quality. Also, at the back of every picture, the number of the picture and the name of the first author should be noted in pencil, with an arrow showing the top of the picture. The identity of patients should not be recognizable from their pictures nor should their names be stated.

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C. Manuscript Submission and Publication All manuscripts should be accompanied by a floppy disk or CD, as well as by a letter, signed by all the authors, in which it is stated that the paper has not been published in part or in whole, or is not under consideration by another journal and that the authors accept its publication in “Paediatriki”. Any funding, sponsorship or other financial support should be acknowledged. Once the manuscript has been accepted, the corrected version, rewritten according to the reviewers’ recommendations should be submitted to the Editorial Board accompanied by a floppy disk or CD, containing the paper in Word format, along with a covering letter specifying in detail the modifications or objections to the reviewers’ suggestions. Delay in submission of the modified paper exceeding 30 days entails new submission. Authors will be charged film and reprint expenses, paid upon dispatch of the first proof directly to the printer. Manuscripts of papers which have not been approved for publication are not returned to the author. The accompanying figures and photographs can be returned upon request within six months. Manuscripts submitted for review and publication in “Paediatriki” should be sent in three copies to the following address: Editorial Board, Greek Paediatric Society 92, Michalakopoulou Street, 115 28 Athens, Greece

Before submitting your paper, make sure it contains: 1. 3 copies of the text of the paper, printed according to instructions. 2. A floppy disk or CD with the entire material of the paper (text, tables, pictures). 3. A covering letter and a statement that the paper has not been previously published. 4. The title page (on a separate page), which includes: a. the title and short title of the paper; b. the name and surname (full name)of the author(s); c. the academic centre(s) of origin; d. the corresponding authors’ name, address and telephone number; 5. English and Greek abstracts, with the following structure: background, methods, results and conclusions (double space, separate page) and keywords. 6. List of abbreviations (double space, separate page). 7. Text (double space, separate page). 8. Acknowledgements and reference to funding, sponsorships or other financial sources. 9. References (double space, separate page). 10. Tables (one per page) in three copies. 11. Figures with an arrow at the back showing the top, numbered, in two copies. 12. Figure titles (double space - on separate pages) in three copies.

ª·Ú›· ¶··Ê›ÏË °È· ÏËÚÔÊÔÚ›Â˜: www.euran.com ªaria Papafili For information: www.euran.com

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√ ÚfiÏÔ˜ ÙË˜ ·fiÙˆÛË˜ ÛÙË ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ· µ. ¢ÚfiÛÔ˘ - ∞Á·Î›‰Ô˘1, ∂. ™ˆÙËÚ›‰Ô˘2

¶ÂÚ›ÏË„Ë: ¶·Ú¿ ÙÈ˜ ÛËÌ·ÓÙÈÎ¤˜ ÂÍÂÏ›ÍÂÈ˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË, ÔÈ Û˘ÁÁÂÓÂ›˜ ‰È·Ì·ÚÙ›Â˜ ·Ú·Ì¤ÓÔ˘Ó ÌÈ· ÛËÌ·ÓÙÈÎ‹ ·ÈÙ›· ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÛÈÌfiÙËÙ·˜ ÙˆÓ ÓÂÔÁÓÒÓ ‰È·‚ËÙÈÎÒÓ ÌËÙ¤ÚˆÓ. Œ¯ÂÈ ÂÓÔ¯ÔÔÈËıÂ› ¤Ó· Ï‹ıÔ˜ ÌÂÙ·‚ÔÏÈÎÒÓ Î·È ¿ÏÏˆÓ ÌË¯·ÓÈÛÌÒÓ Ô˘ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ˘ÂÚ- ‹ ˘Ô-ÁÏ˘Î·ÈÌ›· ÙË˜ ÌËÙ¤Ú·˜, ÙËÓ ˘ÂÚÎÂÙÔÓ·ÈÌ›·, ÙËÓ ·ÓÂ¿ÚÎÂÈ· ıÚÂÙÈÎÒÓ Ô˘ÛÈÒÓ, fiˆ˜ ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ ÔÍ¤Ô˜ Î·È ÙË˜ Ì˘Ô˚ÓÔÛÈÙfiÏË˜, ÙËÓ ·˘ÍËÌ¤ÓË ·Ú·ÁˆÁ‹ ÂÏÂ˘ı¤ÚˆÓ ÚÈ˙ÒÓ ÔÍ˘ÁfiÓÔ˘ Î.¿. ªÈ· Î·ÈÓÔ‡ÚÁÈ· ˘fiıÂÛË Ô˘ ·Ó·‰‡ÂÙ·È Û¯ÂÙÈÎ¿ ÌÂ ÙËÓ ·ıÔÁ¤ÓÂÈ· ÙˆÓ Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ ÛÂ ‰È·‚ËÙÈÎ¤˜ Î˘‹ÛÂÈ˜ Â›Ó·È Ë Â·ÁˆÁ‹ ÙË˜ ‰È·‰ÈÎ·Û›·˜ ÙË˜ ·fiÙˆÛË˜ ÏfiÁˆ ÙË˜ ˘ÂÚÁÏ˘Î·ÈÌ›·˜. ™ÙÔ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ·Ó¿Ù˘ÍË˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘, Ë ˘ÂÚÁÏ˘Î·ÈÌ›· Ô‰ËÁÂ› ÛÂ ·‡ÍËÛË ÙË˜ ¤ÎÊÚ·ÛË˜ ÙÔ˘ ÁÔÓÈ‰›Ô˘ p53, ÙÔ ÔÔ›Ô Â¿ÁÂÈ ÙËÓ ·˘ÍËÌ¤ÓË ¤ÎÊÚ·ÛË ÙË˜ ÚÔ·ÔÙˆÙÈÎ‹˜ ÚˆÙÂ˝ÓË˜ µ∞Ã. ™ÙÔ ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ·Ó¿Ù˘ÍË˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘, Ë ˘ÂÚÁÏ˘Î·ÈÌ›· ÂÏ·ÙÙÒÓÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓÈ‰›Ô˘ Pax3, ÙÔ ÔÔ›Ô Ô‰ËÁÂ› ÛÙËÓ ·˘ÍËÌ¤ÓË ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓÈ‰›Ô˘ Cdc46 ÛÙÔ ÚÒÈÌÔ ÛÙ¿‰ÈÔ Î·È ÛÙË ÌÂÈˆÌ¤ÓË ¤ÎÊÚ·ÛË ÙÔ˘ Dep1 ÛÙÔ fi„ÈÌÔ ÛÙ¿‰ÈÔ ·Ó¿Ù˘ÍË˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘, ÌÂ Û˘Ó¤ÂÈ· ÙËÓ Â·ÁˆÁ‹ ÙË˜ ‰È·‰ÈÎ·Û›·˜ ÙË˜ ·fiÙˆÛË˜.

1. ∞’ ¡ÂÔÁÓÔÏÔÁÈÎ‹ ∫ÏÈÓÈÎ‹ Î·È ∂ÓÙ·ÙÈÎ‹ ¡ÔÛËÏÂ›· ¡ÂÔÁÓÒÓ ∞.¶.£., “πÔÎÚ¿ÙÂÈÔ” °.¶.¡. £ÂÛÛ·ÏÔÓ›ÎË˜ 2. ªÂÙ·Ù˘¯È·Î‹ ÊÔÈÙ‹ÙÚÈ· (¡.¶.ª.™.) ÙË˜ π·ÙÚÈÎ‹˜ ™¯ÔÏ‹˜ ∞.¶.£., “πÔÎÚ¿ÙÂÈÔ” °.¶.¡. £ÂÛÛ·ÏÔÓ›ÎË˜ AÏÏËÏÔÁÚ·Ê›·: µ. ¢ÚﬁÛÔ˘-∞Á·Î›‰Ô˘ °ÏËÓÔ‡ 28, ∆∫ 543 52, £ÂÛÛ·ÏÔÓ›ÎË ∂-mail: agaki@med.auth.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 31-05-2005 Date of approval: 07-04-2006

§¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ¢È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ·, Û˘ÁÁÂÓÂ›˜ ‰È·Ì·ÚÙ›Â˜, ˘ÂÚÁÏ˘Î·ÈÌ›·, ·ﬁÙˆÛË.

The role of apoptosis in diabetic embryopathy 1

V. Drossou - Agakidou , E. Sotiridou

Abstract: Despite significant improvements in the management of diabetes mellitus, congenital malformations remain a major cause of morbidity and mortality among the infants of diabetic mothers. A variety of metabolic disturbances, including maternal hyper- and hypoglycaemia and hyperketonaemia, nutritional deficiencies such as arachidonic acid and myo-inositol deficiencies, and increased oxygen free radical production, have been implicated. One emerging hypothesis for the aetiology of diabetes-associated malformations is that of hyperglycaemia induced apoptosis. During the pre-implantation stage of development, maternal hyperglycaemia triggers the expression of the proapoptotic protein BAX, which leads to activation of caspases, DNA fragmentation and morphological changes consistent with apoptosis. During post-implantation embryogenesis maternal hyperglycaemia results in decreased Pax3 expression, leading to increased Cdc46 expression (early event) and decreased Dep1 expression (late event), with resultant increased apoptosis in the developing embryos. Key words: Diabetic embryopathy, congenital malformations, hyperglycemia, apoptosis.

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ BAX: BCL2: Cdc46: Dep1: GLUT 1: Hif-1a: Pax3: TNF: Waf-1:

BCL2-associated X protein B-cell leukemia/lymphoma 2 Cell division cycle 46 Diabetic embryopathy 1 Glucose transporter type 1 Hypoxia-inducible factor 1 alpha Paired box gene 3 Tumor necrosis factor Waf-1 (a cyclin-dependent kinase inhibitor)

1. 1st Department of Neonatology & Neonatal Intensive Care Unit, Aristotle University of Thessaloniki, Ippokratio Hospital, Thessaloniki 2. Postgraduate student in the Faculty of Medicine, Aristotle University of Thessaloniki, Ippokratio Hospital, Thessaloniki Correspondence: V. Drossou-Agakidou 28 Glinou St, 543 52 Thessaloniki, Greece ∂-mail: agaki@med.auth.gr Date of submission: 31-05-2005 Date of approval: 07-04-2006

∂ÈÛ·ÁˆÁ‹ ¶·Ú¿ ÙÈ˜ ÛËÌ·ÓÙÈÎ¤˜ ÂÍÂÏ›ÍÂÈ˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË, ÔÈ Û˘ÁÁÂÓÂ›˜ ‰È·Ì·ÚÙ›Â˜ ·Ú·Ì¤ÓÔ˘Ó ÌÈ· ÛËÌ·ÓÙÈÎ‹ ·ÈÙ›· ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÛÈÌfiÙËÙ·˜ ÙˆÓ ÓÂÔÁÓÒÓ ‰È·‚ËÙÈÎÒÓ ÌËÙ¤ÚˆÓ. ∏ Û˘¯ÓfiÙËÙ· ÌÂÈ˙fiÓˆÓ ‰È·Ì·ÚÙÈÒÓ Â›Ó·È 6-9%, ‰ËÏ·‰‹ 3-4 ÊÔÚ¤˜ ˘„ËÏfiÙÂÚË ·’ fi,ÙÈ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, Î·È Â˘ı‡ÓÔÓÙ·È ÁÈ· ÙÔ 33-66% ÙˆÓ ÂÚÈÁÂÓÓËÙÈÎÒÓ ¶·È‰È·ÙÚÈÎ‹ 2006;69:409-416

410

µ. ¢ÚﬁÛÔ˘-∞Á·Î›‰Ô˘, ∂. ™ˆÙËÚ›‰Ô˘

ı·Ó¿ÙˆÓ ÙˆÓ ÓÂÔÁÓÒÓ ‰È·‚ËÙÈÎÒÓ ÌËÙ¤ÚˆÓ (1). √ Î‡ÚÈÔ˜ ÏfiÁÔ˜ ÁÈ· ÙËÓ ·‰˘Ó·Ì›· ÈÎ·ÓÔÔÈËÙÈÎ‹˜ ÌÂ›ˆÛË˜ ÙË˜ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ Û˘ÁÁÂÓÒÓ ‰˘ÛÏ·ÛÈÒÓ Â›Ó·È Ë ÔÏ‡ ÚÒÈÌË ·Ó¿Ù˘Í‹ ÙÔ˘˜, ÙËÓ 1Ë-6Ë Â‚‰ÔÌ¿‰· ÙË˜ Î‡ËÛË˜. ∆Ô Ê¿ÛÌ· ÙˆÓ ‰È·Ì·ÚÙÈÒÓ ÛÙË ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ· Â›Ó·È Â˘Ú‡ Î·È ·ÊÔÚ¿ Î˘Ú›ˆ˜ ÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi, ÙÔ ÎÂÓÙÚÈÎfi ÓÂ˘ÚÈÎfi Û‡ÛÙËÌ· Î·È ÙÔ Ì˘ÔÛÎÂÏÂÙÈÎfi Û‡ÛÙËÌ·. ∏ ‰È·Ì·ÚÙ›· Ë ÔÔ›· ıÂˆÚÂ›Ù·È fiÙÈ Â›Ó·È ¯·Ú·ÎÙËÚÈÛÙÈÎ‹ ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÂÌ‚Ú˘Ô¿ıÂÈ·˜ Â›Ó·È ÙÔ Û‡Ó‰ÚÔÌÔ Ô˘Ú·›·˜ ·ÏÈÓ‰ÚfiÌËÛË˜ ‹ ·ÁÂÓÂÛ›·˜ ÙÔ˘ ÈÂÚÔ‡ ÔÛÙÔ‡, 200-400 ÊÔÚ¤˜ ÈÔ Û˘¯Ófi ÛÙ· ÓÂÔÁÓ¿ ‰È·‚ËÙÈÎÒÓ ÌËÙ¤ÚˆÓ Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi (1). ∏ ·ıÔÁ¤ÓÂÈ· ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÂÌ‚Ú˘Ô¿ıÂÈ·˜ ·ÔÙ¤ÏÂÛÂ ·ÓÙÈÎÂ›ÌÂÓÔ Ï‹ıÔ˘˜ ÂÈÚ·Ì·ÙÈÎÒÓ Î·È ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ Î·Ù¿ Ù· ÙÂÏÂ˘Ù·›· 30 ¯ÚfiÓÈ·. Œ¯ÂÈ ÂÓÔ¯ÔÔÈËıÂ› Ï‹ıÔ˜ ÌÂÙ·‚ÔÏÈÎÒÓ Î·È ¿ÏÏˆÓ ÌË¯·ÓÈÛÌÒÓ, ÔÈ ÔÔ›ÔÈ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ˘ÂÚ- ‹ ˘ÔÁÏ˘Î·ÈÌ›· ÙË˜ ÌËÙ¤Ú·˜, ÙËÓ ˘ÂÚÎÂÙÔÓ·ÈÌ›·, ÙËÓ ·ÓÂ¿ÚÎÂÈ· ıÚÂÙÈÎÒÓ Ô˘ÛÈÒÓ, fiˆ˜ ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ ÔÍ¤Ô˜ Î·È ÙË˜ Ì˘Ô˚ÓÔÛÈÙfiÏË˜, ÙËÓ ·˘ÍËÌ¤ÓË ·Ú·ÁˆÁ‹ ÂÏÂ˘ı¤ÚˆÓ ÚÈ˙ÒÓ ÔÍ˘ÁfiÓÔ˘ Î.¿. (2). ¶·ÚfiÏ· ·˘Ù¿, Ô ·ÎÚÈ‚‹˜ ÌË¯·ÓÈÛÌfi˜ ÙˆÓ Û˘ÁÁÂÓÒÓ ‰˘ÛÏ·ÛÈÒÓ ÛÙË ‰È·‚ËÙÈÎ‹ Î‡ËÛË ‰ÂÓ Â›Ó·È ·ÎfiÌ· ÁÓˆÛÙfi˜. ªÈ· Î·ÈÓÔ‡ÚÁÈ· ˘fiıÂÛË Ô˘ ·Ó·‰‡ÂÙ·È Û¯ÂÙÈÎ¿ ÌÂ ÙËÓ ·ıÔÁ¤ÓÂÈ· ÙˆÓ Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ ÛÂ ‰È·‚ËÙÈÎ¤˜ Î˘‹ÛÂÈ˜ Â›Ó·È Ë Â·ÁˆÁ‹ ÙË˜ ‰È·‰ÈÎ·Û›·˜ ÙË˜ ·fiÙˆÛË˜ ÏfiÁˆ ÙË˜ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ (3,4). ∏ ·fiÙˆÛË Â›Ó·È ÌÈ· ÚÔ‰È·ÁÂÁÚ·ÌÌ¤ÓË Î·È ÁÂÓÂÙÈÎ¿ ÂÏÂÁ¯fiÌÂÓË ·¿ÓÙËÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÛÂ ÂÈ‰ÈÎ¿ ÂÚÈ‚·ÏÏÔÓÙÈÎ¿ Î·È ·Ó·Ù˘ÍÈ·Î¿ ÂÚÂı›ÛÌ·Ù·, Ë ÔÔ›· Â¿ÁÂÙ·È ·fi ÔÏÏÔ‡˜ ·Ú¿ÁÔÓÙÂ˜, fiˆ˜ Â›Ó·È Ù· ÁÏ˘ÎÔÎÔÚÙÈÎÔÂÈ‰‹, Ë ˘ÂÚÈÒ‰Ë˜ ·ÎÙÈÓÔ‚ÔÏ›·, Ë ·Ô˘Û›· ÔÚÈÛÌ¤ÓˆÓ ·˘ÍËÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, Ë ¤ÎÊÚ·ÛË ÙˆÓ ÁÔÓÈ‰›ˆÓ c-myc Î·È p53, Ë ÈÔÁÂÓ‹˜ ÌfiÏ˘ÓÛË Î.¿. ∏ ·fiÙˆÛË Â›Ó·È ÌÈ· Û·ÊÒ˜ ÚÔÁÚ·ÌÌ·ÙÈ˙fiÌÂÓË ‰È·‰ÈÎ·Û›·, Ë ÔÔ›· ·ÔÛÎÔÂ› ÛÙÔÓ ı¿Ó·ÙÔ Î·È ÛÙËÓ ·ÔÌ¿ÎÚ˘ÓÛË Î˘ÙÙ¿ÚˆÓ, ÌÂ ÙËÓ ÂÏ¿¯ÈÛÙË ‰˘Ó·Ù‹ ‚Ï¿‚Ë ÛÙÔ˘˜ ÂÚÈ‚¿ÏÏÔÓÙÂ˜ ÈÛÙÔ‡˜, ÁÂÁÔÓfi˜ Ô˘ ˘ÔÁÚ·ÌÌ›˙ÂÈ ÙË ÛËÌ·Û›· ÙË˜ ÛÙË Ê˘ÛÈÔÏÔÁÈÎ‹ ·Ó¿Ù˘ÍË ÙˆÓ ÈÛÙÒÓ. ™ÙËÓ ·fiÙˆÛË, ÙÔ Î‡ÙÙ·ÚÔ Û˘ÌÌÂÙ¤¯ÂÈ ÂÓÂÚÁ¿ ÛÙÔ Û˘ÁÎÂÎÚÈÌ¤ÓÔ ÂÓ‰ÔÁÂÓ¤˜ ÚfiÁÚ·ÌÌ· ·˘ÙÔÎ·Ù·ÛÙÚÔÊ‹˜ ÙÔ˘, ·Ú¿ÁÔÓÙ·˜ Ù· ··Ú·›ÙËÙ· Ì·ÎÚÔÌfiÚÈ· Î·È ÙËÓ ··ÈÙÔ‡ÌÂÓË ÂÓ¤ÚÁÂÈ·. °È· ÙÔÓ ÏfiÁÔ ·˘Ùfi, Ë ·fiÙˆÛË ÔÓÔÌ¿˙ÂÙ·È Î·È “ÂÓÂÚÁfi˜ Î˘ÙÙ·ÚÈÎfi˜ ı¿Ó·ÙÔ˜” (5). À¿Ú¯Ô˘Ó ÔÏÏ¿ ÂÈÚ·Ì·ÙÈÎ¿ ‰Â‰ÔÌ¤Ó· ¶·È‰È·ÙÚÈÎ‹ 2006;69:409-416

Ô˘ ˘Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ Ë ·fiÙˆÛË ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙË ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ·, ÙfiÛÔ Î·Ù¿ ÙÔ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎfi fiÛÔ Î·È Î·Ù¿ ÙÔ ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ÙË˜ ÂÌ‚Ú˘˚Î‹˜ ·Ó¿Ù˘ÍË˜. √È ÌË¯·ÓÈÛÌÔ› ÌÂ ÙÔ˘˜ ÔÔ›Ô˘˜ Ë ˘ÂÚÁÏ˘Î·ÈÌ›· Ô‰ËÁÂ› ÛÂ ·‡ÍËÛË ÙË˜ ·fiÙˆÛË˜ ‰È·Ê¤ÚÔ˘Ó ÌÂÙ·Í‡ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎÔ‡ Î·È ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎÔ‡ ÛÙ·‰›Ô˘, ·ÏÏ¿ ‰ÂÓ ¤¯Ô˘Ó ‰ÈÂ˘ÎÚÈÓÈÛÙÂ› Ï‹Úˆ˜. ·) ¶ÚÔÂÌÊ˘ÙÂ˘ÙÈÎ‹ ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ· ∆Ô ÚÔÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ÂÎÙÂ›ÓÂÙ·È ·fi ÙË Û‡ÏÏË„Ë, ÙË ‰ËÌÈÔ˘ÚÁ›· ‚Ï·ÛÙÔÌÂÚÈ‰›ˆÓ Î·È ‚Ï·ÛÙÔÎ‡ÛÙË˜ Ì¤¯ÚÈ ÙËÓ ÂÌÊ‡ÙÂ˘ÛË. ªÂÏ¤ÙÂ˜ ÛÂ ÂÈÚ·Ì·ÙÈÎ¿ ÌÔÓÙ¤Ï· ˙ÒˆÓ ÛÙÔ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ÙË˜ ·Ó¿Ù˘ÍË˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Ë ÌËÙÚÈÎ‹ ˘ÂÚÁÏ˘Î·ÈÌ›· Ô‰ËÁÂ› ÛÙËÓ Î·ÙÈÔ‡Û· Ú‡ıÌÈÛË ÙˆÓ ÂÌ‚Ú˘˚ÎÒÓ ÌÂÙ·ÊÔÚ¤ˆÓ ÁÏ˘Îfi˙Ë˜ GLUT1-2 Î·È -3 ÛÙÔ ÛÙ¿‰ÈÔ ·Ó¿Ù˘ÍË˜ ÙË˜ ‚Ï·ÛÙÔÎ‡ÛÙË˜ (6). ™Â in vitro ÌÂÏ¤ÙÂ˜, Î·ÏÏÈ¤ÚÁÂÈ· ÂÌ‚Ú‡ˆÓ ÛÙÔ ÛÙ¿‰ÈÔ ÙˆÓ ‰‡Ô-Î˘ÙÙ¿ÚˆÓ ÛÂ ˘„ËÏ¤˜ Û˘ÁÎÂÓÙÚÒÛÂÈ˜ ÁÏ˘Îfi˙Ë˜ (30 ‹ 52 mª) ÁÈ· 72 ÒÚÂ˜, Â›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÏ¿ÙÙˆÛË ÙË˜ ¤ÎÊÚ·ÛË˜ ÙÔ˘ mRNA Î·È ÙË˜ Û‡ÓıÂÛË˜ ÙˆÓ ÚˆÙÂ˚ÓÒÓ. ÕÏÏÂ˜ ÌÂÏ¤ÙÂ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ÌÂ›ˆÛË ÙˆÓ ÌÂÙ·ÊÔÚ¤ˆÓ Ô‰‹ÁËÛÂ ÛÂ ÌÈ· ÛËÌ·ÓÙÈÎ‹ ÙÒÛË ÙˆÓ ÂÏÂ˘ı¤ÚˆÓ ÂÈ¤‰ˆÓ ÁÏ˘Îfi˙Ë˜ ÛÂ ‚Ï·ÛÙÔÎ‡ÛÙÂÈ˜ ÔÓÙÈÎÒÓ, ÔÈ ÔÔ›ÔÈ Â›¯·Ó ·Ó·Ù‡ÍÂÈ ˘ÂÚÁÏ˘Î·ÈÌ›· Â›ÙÂ ÌÂ ¤Á¯˘ÛË ÛÙÚÂÙÔ˙ÔÙÔÎ›ÓË˜ Â›ÙÂ ÌÂ Î·ÏÏÈ¤ÚÁÂÈ· ÙˆÓ ÂÌ‚Ú‡ˆÓ ÛÙÔ ÛÙ¿‰ÈÔ ‰‡Ô-Î˘ÙÙ¿ÚˆÓ ÛÂ ˘„ËÏ¿ Â›Â‰· ÁÏ˘Îfi˙Ë˜ (6,7). ∫·È ¿ÏÏÂ˜ ÌÂÏ¤ÙÂ˜ ¤¯Ô˘Ó Û˘Ó‰¤ÛÂÈ ÙË ÌÂ›ˆÛË ÙË˜ ÌÂÙ·ÊÔÚ¿˜ ÙË˜ ÁÏ˘Îfi˙Ë˜ ÌÂ ÚfiˆÚÔ ÚÔÁÚ·ÌÌ·ÙÈÛÌ¤ÓÔ Î˘ÙÙ·ÚÈÎfi ı¿Ó·ÙÔ (8-10). ∞fi Ù· Â˘Ú‹Ì·Ù· ·˘Ù¿ Û˘ÌÂÚ·›ÓÂÙ·È fiÙÈ Ë ˘ÂÚÁÏ˘Î·ÈÌ›·, ÌÂÈÒÓÔÓÙ·˜ ÙÔ˘˜ ÌÂÙ·ÊÔÚÂ›˜ ÁÏ˘Îfi˙Ë˜ ÛÙË ‚Ï·ÛÙÔÎ‡ÛÙË, ÏÂÈÙÔ˘ÚÁÂ› Û·Ó ¤Ó· Û‹Ì· ı·Ó¿ÙÔ˘, ÙÔ ÔÔ›Ô ‰ÈÂÁÂ›ÚÂÈ ÙËÓ ·ÔÙˆÙÈÎ‹ Ô‰fi Ô˘ ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ÚˆÙÂ˝ÓË BAX (6,11). ¶Ú¿ÁÌ·ÙÈ, ‚Ï·ÛÙÔÎ‡ÛÙÂÈ˜ Ô˘ ‚Ú¤ıËÎ·Ó ÛÂ Û˘Óı‹ÎÂ˜ ·˘ÍËÌ¤ÓˆÓ ÂÈ¤‰ˆÓ ÁÏ˘Îfi˙Ë˜, in vivo Î·È in vitro, ·ÚÔ˘Û›·Û·Ó ·‡ÍËÛË ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓÈ‰›Ô˘ Bax ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÔÌ¿‰· ÂÏ¤Á¯Ô˘ (3). ∏ BAX Â›Ó·È ÚÔ·ÔÙˆÙÈÎfi Ì¤ÏÔ˜ ÙË˜ BCL2 ÔÈÎÔÁ¤ÓÂÈ·˜ ÙˆÓ ÚˆÙÂ˚ÓÒÓ. ∂¿ÁÂÈ ÙËÓ ·fiÙˆÛË Î·È ÛÂ ‰È¿Ï˘Ì· Û¯ËÌ·Ù›˙ÂÈ ¤Ó· ÂÙÂÚÔ‰ÈÌÂÚ¤˜ Û‡ÌÏÔÎÔ ÌÂ ÙËÓ BCL2 ·Ó·ÛÙ¤ÏÏÔÓÙ·˜ ÌÂ ÙÔÓ ÙÚfiÔ ·˘Ùfi ÙËÓ ·ÓÙÈ·ÔÙˆÙÈÎ‹ ÙË˜ ‰Ú¿ÛË (12-14). ∏ BAX Û˘Ó‰¤ÂÈ ÙË Ú‡ıÌÈÛË ÙË˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ Î·È ÙË˜ ·fiÙˆÛË˜ ÌÂ ÙËÓ

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AﬁÙˆÛË ÛÙË ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ·

ÂÈÙ‹ÚËÛË ÙË˜ ·ÎÂÚ·ÈfiÙËÙ·˜ ÙÔ˘ DNA ·fi ÙÔ p53 ‹/Î·È ·fi ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙÂ˜ ÌÂ ‰Ú¿ÛË ·ÚfiÌÔÈ· ÙÔ˘ p53. ∏ ‰È·‰ÈÎ·Û›· ÙË˜ ·fiÙˆÛË˜ ··ÈÙÂ› ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓÈ‰›Ô˘ Bax. ∞˘Ùfi ÚÔÎ‡ÙÂÈ ·fi ÌÂÏ¤ÙÂ˜ ÛÂ ¤Ì‚Ú˘· ÔÓÙÈÎÒÓ Ô˘ ‰ÂÓ Â›¯·Ó ÙÔ ÁÔÓ›‰ÈÔ Bax (Bax -/-), ÛÙ· ÔÔ›· Ë ¤ÎıÂÛË ÛÂ ˘„ËÏ¤˜ Û˘ÁÎÂÓÙÚÒÛÂÈ˜ ÁÏ˘Îfi˙Ë˜ ‰ÂÓ Â›¯Â Î·Ì›· ‰˘ÛÌÂÓ‹ Â›‰Ú·ÛË (3). ™Â ÌÔÓÙ¤ÏÔ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎ‹˜ ÂÌ‚Ú˘Ô¿ıÂÈ·˜ ÔÓÙÈÎÒÓ, ¤¯ÂÈ ‚ÚÂıÂ› Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÙË˜ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ Î·È ÙË˜ ¤ÎÊÚ·ÛË˜ ÙÔ˘ ÁÔÓÈ‰›Ô˘ p53 (15). ∆· ¤Ì‚Ú˘· Ù· ÔÔ›· ÛÙÂÚÔ‡ÓÙ·Ó ÙË˜ ¤ÎÊÚ·ÛË˜ ÙÔ˘ p53 ‹Ù·Ó ·ÓıÂÎÙÈÎ¿ ÛÙËÓ Â›‰Ú·ÛË ÙË˜ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ in vivo Î·È in vitro. ∆Ô ›‰ÈÔ ·Ú·ÙËÚ‹ıËÎÂ Î·È ÛÙÔ˘˜ Bax -/- ÔÓÙÈÎÔ‡˜. ∆Ô ÁÔÓ›‰ÈÔ p53 Û˘ÌÌÂÙ¤¯ÂÈ ÛÂ ‰È¿ÊÔÚ· Î˘ÙÙ·ÚÈÎ¿ ÁÂÁÔÓfiÙ·, ÛÙ· ÔÔ›· ÂÚÈÏ·Ì‚¿ÓÂÙ·È Ë ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÌË¯·ÓÈÛÌÔ‡ ÂÈ‰ÈfiÚıˆÛË˜ ÙÔ˘ DNA Î·È Ë ·fiÙˆÛË (16). ∏ Ê˘ÛÈÔÏÔÁÈÎ‹ ÔÁÎÔÎ·Ù·ÛÙ·ÏÙÈÎ‹ ‰Ú¿ÛË ÙÔ˘ p53 ·ÛÎÂ›Ù·È ÌÂ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Waf1 ÁÔÓÈ‰›Ô˘ (17), ÙÔ ÔÔ›Ô ÌÂ ÙË ÛÂÈÚ¿ ÙÔ˘ ·Ó·ÛÙ¤ÏÏÂÈ ÙË ‰Ú¿ÛË ÂÈ‰ÈÎÒÓ ÎÈÓ·ÛÒÓ (Î˘ÎÏ›ÓÂ˜ 6 Î·È 8) ÛÙÈ˜ G1 Î·È G2 Ê¿ÛÂÈ˜ ÙÔ˘ Î˘ÙÙ·ÚÈÎÔ‡ Î‡ÎÏÔ˘, ÁÈ· Ó· Á›ÓÂÈ Ë ÂÈ‰ÈfiÚıˆÛË ÙË˜ ‚Ï¿‚Ë˜ ÙÔ˘ DNA (18). ∞Ó ·˘Ù‹ Â›Ó·È ·ÓÂÈÙ˘¯‹˜, ÙfiÙÂ ÙÔ p53 ÍÂÎÈÓ¿ ÚÔÁÚ·ÌÌ·ÙÈÛÌ¤ÓÔ Î˘ÙÙ·ÚÈÎfi ı¿Ó·ÙÔ ÂÓÂÚÁÔÔÈÒÓÙ·˜ ÙÔÓ ˘Ô‰Ô¯¤· Fas Ô˘ ·ÔÙÂÏÂ› Ì¤ÏÔ˜ ÙË˜ ˘ÂÚÔÈÎÔÁ¤ÓÂÈ·˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ ·Ú¿ÁÔÓÙ· Ó¤ÎÚˆÛË˜ ÙˆÓ fiÁÎˆÓ (TNF receptor superfamily, member 6) Î·È ÙÔ ÁÔÓ›‰ÈÔ Bax, Ô‰ËÁÒÓÙ·˜ ÌÂ ÙÔÓ ÙÚfiÔ ·˘Ùfi ÛÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙË˜ Î·Û¿ÛË˜-3 (19). ŒÙÛÈ, ÙÔ ÁÔÓ›‰ÈÔ p53 ·ÔÙÚ¤ÂÈ ÙËÓ ÂÚ·ÈÙ¤Úˆ ÂÈ‚›ˆÛË Î·È ·Ó··Ú·ÁˆÁ‹ ÂÓfi˜ Î˘ÙÙ¿ÚÔ˘ ÌÂ ÌfiÓÈÌË ‚Ï¿‚Ë ÛÙÔ ÁÔÓÈ‰›ˆÌ¿ ÙÔ˘. ∆Ô ÁÔÓ›‰ÈÔ p53 ¤¯ÂÈ ¿ÌÂÛË Â›‰Ú·ÛË ÛÙËÓ ·fiÙˆÛË, ÂÏ·ÙÙÒÓÔÓÙ·˜ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓÈ‰›Ô˘ Bcl-2 Î·È ·˘Í¿ÓÔÓÙ·˜ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓÈ‰›Ô˘ Bax. ∂ÂÈ‰‹ ÙÔ p53 Â›Ó·È ¤Ó·˜ ÌÂÙ·ÁÚ·ÊÈÎfi˜ Ú˘ıÌÈÛÙ‹˜ ÙÔ˘ Bax, Â›Ó·È Èı·Ófi fiÙÈ Ë ÌËÙÚÈÎ‹ ˘ÂÚÁÏ˘Î·ÈÌ›·, ÌÂ ÙË ÌÂ›ˆÛË ÙˆÓ ÂÓ‰ÔÎ˘ÙÙ¿ÚÈˆÓ ÂÈ¤‰ˆÓ ÁÏ˘Îfi˙Ë˜ ÛÙÔ ¤Ì‚Ú˘Ô, ÚÔÎ·ÏÂ› ¤ÎÊÚ·ÛË ÙÔ˘ Hif-1·, Ô˘ Ô‰ËÁÂ› ÛÂ ·˘ÍËÌ¤ÓË ¤ÎÊÚ·ÛË ÙÔ˘ p53, ÙÔ ÔÔ›Ô ÛÙË Û˘Ó¤¯ÂÈ· Â¿ÁÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Bax Î·È, ÙÂÏÈÎ¿, ÙË ‰È·‰ÈÎ·Û›· ÙË˜ ·fiÙˆÛË˜ Ì¤Û· ÛÙË ‚Ï·ÛÙÔÎ‡ÛÙË (11,20). ∏ ·ÔÙˆÙÈÎ‹ ‰Ú¿ÛË ÙË˜ ÚˆÙÂ˝ÓË˜ BAX ÔÊÂ›ÏÂÙ·È Î˘Ú›ˆ˜ ÛÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Î·Û·ÛÒÓ (11). √È Î·Û¿ÛÂ˜ ·ÔÙÂÏÔ‡Ó ÌÈ· ÔÌ¿‰· ÚˆÙÂÔÏ˘ÙÈÎÒÓ ÂÓ˙‡ÌˆÓ Ô˘ ·›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ÔÙˆÙÈÎ‹ ‰ÈÂÚÁ·Û›· (21). √È Î·Û¿ÛÂ˜ ‚Ú›ÛÎÔÓÙ·È ÛÂ ·‰Ú·Ó‹ Î·Ù¿ÛÙ·ÛË, Ì¤¯ÚÈ˜ fiÙÔ˘

Î¿ÔÈÔ Â·ÁˆÁÈÎfi Û‹Ì· ÂÓÂÚÁÔÔÈ‹ÛÂÈ Ì›· ·fi ·˘Ù¤˜. ∆fiÙÂ ·Ú¯›˙ÂÈ Ë ‰È·‰Ô¯ÈÎ‹ ÂÓÂÚÁÔÔ›ËÛË Î·È ¿ÏÏˆÓ Î·Û·ÛÒÓ, Ô˘ ¤¯Ô˘Ó ˆ˜ ÛÙfi¯Ô Î˘Ú›ˆ˜ ‰‡Ô ÌÂÁ¿ÏÂ˜ Î·ÙËÁÔÚ›Â˜ ÚˆÙÂ˚ÓÒÓ: ·) ÚˆÙÂ˝ÓÂ˜ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙË ‰ÔÌ‹ Î·È ÙËÓ ÔÚÁ¿ÓˆÛË ÙÔ˘ Î˘ÙÙ¿ÚÔ˘ (22) Î·È ‚) Î·Ù·Ï˘ÙÈÎ¤˜ ÚˆÙÂ˝ÓÂ˜ Ô˘ ÂÌÏ¤ÎÔÓÙ·È ÛÙÔ˘˜ ÌË¯·ÓÈÛÌÔ‡˜ ÔÌÔÈfiÛÙ·ÛË˜ ÙÔ˘ Î˘ÙÙ¿ÚÔ˘, ÌÂÙ·Í‡ ÙˆÓ ÔÔ›ˆÓ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÌË¯·ÓÈÛÌÔ› ÂÈ‰ÈfiÚıˆÛË˜ ÙÔ˘ DNA (23), ÂÏ¤Á¯Ô˘ ÙÔ˘ Î˘ÙÙ·ÚÈÎÔ‡ Î‡ÎÏÔ˘ (24) Î·È ¿ÏÏÔÈ ÛËÌ·ÓÙÈÎÔ› ‚ÈÔ¯ËÌÈÎÔ› ÌË¯·ÓÈÛÌÔ› (25). √È Î·Û¿ÛÂ˜ ÂÓÙÔ›˙ÔÓÙ·È ÛÙÔ Î˘ÙÙ·ÚfiÏ·ÛÌ· Î·È ÛÙ· ÌÈÙÔ¯fiÓ‰ÚÈ· ÌÂ ÙË ÌÔÚÊ‹ ÂÓfi˜ ·ÓÂÓÂÚÁÔ‡ ÚÔÂÓ˙‡ÌÔ˘ (ÚÔ-Î·Û¿ÛÂ˜) Î·È ÂÓÂÚÁÔÔÈÔ‡ÓÙ·È Ì¤Ûˆ ÙË˜ ÚˆÙÂfiÏ˘Û‹˜ ÙÔ˘˜, Èı·ÓÒ˜ ·fi ¿ÏÏ· Ì¤ÏË ÙË˜ “ÔÈÎÔÁ¤ÓÂÈ·˜” (26). ∫‡ÚÈÔ Ì¤ÏÔ˜ ÙˆÓ Î·Û·ÛÒÓ Â›Ó·È Ë Î·Û¿ÛË-3, Ë ÔÔ›· ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙÔÓ ·ÔÙˆÙÈÎfi Î˘ÙÙ·ÚÈÎfi ı¿Ó·ÙÔ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ·Ó¿Ù˘ÍË˜ (27-29). ™ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Î·Û·ÛÒÓ ·›ÚÓÔ˘Ó Ì¤ÚÔ˜ ÔÈ ˘Ô‰Ô¯Â›˜ Fas Î·È TNF (30). ∆Ô Û‹Ì· ÁÈ· ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Î·Û·ÛÒÓ ÚÔ¤Ú¯ÂÙ·È ·fi ÙË Û‡Ó‰ÂÛË ÛÙÔ˘˜ ·Ú·¿Óˆ ˘Ô‰Ô¯Â›˜ ÙË˜ ÚÔ-Î·Û¿ÛË˜-8, -10 ‹ -2, ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙË ‰ËÌÈÔ˘ÚÁ›· ÂÓfi˜ Û˘ÌÏ¤ÁÌ·ÙÔ˜, ÙÔ ÔÔ›Ô Ô‰ËÁÂ› ÛÙËÓ ·˘ÙÔÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ·Ú·¿Óˆ ÌÔÚ›ˆÓ (31,32). ∂È‰ÈÎfiÙÂÚ·, Ë Î·Û¿ÛË-8 ÌÔÚÂ› Ó· ÂÓÂÚÁÔÔÈ‹ÛÂÈ ·Â˘ıÂ›·˜ ¿ÏÏ· ‰Ú·ÛÙÈÎ¿ ÌfiÚÈ·, fiˆ˜ Â›Ó·È Ë Î·Û¿ÛË-3. ∏ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Î·Û·ÛÒÓ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÂÌÔ‰ÈÛÙÂ› ·fi ÙË BCL-2 (33), ÂÓÒ Î¿Ùˆ ·fi ÔÚÈÛÌ¤ÓÂ˜ Û˘Óı‹ÎÂ˜ Â›Ó·È ‰˘Ó·ÙfiÓ Ë Î·Û¿ÛË-3 Ó· ÂÈ‰Ú¿ÛÂÈ Î·Ù·Ï˘ÙÈÎ¿ ÛÙËÓ ÚˆÙÂ˝ÓË BCL-2, ÚÔÎ·ÏÒÓÙ·˜ ÙËÓ ÂÚ·ÈÙ¤Úˆ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Î·Û·ÛÒÓ Î·È Î·Ù’ Â¤ÎÙ·ÛË ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙË˜ ·fiÙˆÛË˜ (34). ∏ ‰È·‰ÈÎ·Û›· ÙË˜ ·fiÙˆÛË˜ ·Ó·ÛÙ¤ÏÏÂÙ·È ÌÂÚÈÎÒ˜ Â›ÙÂ ÌÂ ÙÔÓ ·Ó·ÛÙÔÏ¤· ÙË˜ Î·Û¿ÛË˜ zVAD-FMK (carbobenzoloxy-Val-AlaAsp-fluoromethylketone), Â›ÙÂ ÌÂ ÙÔÓ ·Ó·ÛÙÔÏ¤· ÙË˜ Û˘ÓıÂÙ¿ÛË˜ ÙË˜ ÎÂÚ·Ì›‰Ë˜ fumonisin B1. À¿Ú¯Ô˘Ó ÂÓ‰Â›ÍÂÈ˜ fiÙÈ Ë Î·Û¿ÛË 1 Î·È Ë ÎÂÚ·Ì›‰Ë ÂÌÏ¤ÎÔÓÙ·È ÛÙË ‰È·‰ÈÎ·Û›· ÙË˜ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ Î·È ÙË˜ ·fiÙˆÛË˜ (3). ∆· ÁÂÁÔÓfiÙ· Ô˘ Ô‰ËÁÔ‡Ó ·fi ÙËÓ ˘ÂÚÁÏ˘Î·ÈÌ›· ÛÙËÓ ·fiÙˆÛË ÛÙÔ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ÙË˜ ·Ó¿Ù˘ÍË˜ (19) Û˘ÓÔ„›˙ÔÓÙ·È ÛÙËÓ ∂ÈÎfiÓ· 1. ∏ ÂÓÂÚÁÔÔ›ËÛË ÙË˜ ·fiÙˆÛË˜ ÛÙÔ ÛÙ¿‰ÈÔ ·˘Ùfi ÙË˜ ·Ó¿Ù˘ÍË˜ ÌÔÚÂ› Ó· Ô‰ËÁ‹ÛÂÈ Â›ÙÂ ÛÂ Û˘ÁÁÂÓÂ›˜ ‰È·Ì·ÚÙ›Â˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘, Â›ÙÂ, Â¿Ó Ë ·ÒÏÂÈ· ÂÌ‚Ú˘˚ÎÒÓ Î˘ÙÙ¿ÚˆÓ Â›Ó·È ÛËÌ·ÓÙÈÎ‹, ÛÂ ·Ô‚ÔÏ‹. ™¯ÂÙÈÎ¤˜ ÌÂÏ¤ÙÂ˜ ¶·È‰È·ÙÚÈÎ‹ 2006;69:409-416

412

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∫·ÙÈÔ‡Û· Ú‡ıÌÈÛË ÙˆÓ ÌÂÙ·ÊÔÚ¤ˆÓ ÁÏ˘Îﬁ˙Ë˜

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∞‡ÍËÛË ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ p53

∞‡ÍËÛË ÛÙËÓ ¤ÎÊÚ·ÛË ÙË˜ ÚÔ·ÔÙˆÙÈÎ‹˜ ÚˆÙÂ˝ÓË˜ µ∞Ã

∂ÓÂÚÁÔÔ›ËÛË ÙˆÓ Î·Û·ÛÒÓ

∞fiÙˆÛË ∂ÈÎfiÓ· 1. ∂ÓÂÚÁÔÔ›ËÛË ÙË˜ ·fiÙˆÛË˜ ÛÙËÓ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎ‹ ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ·.

¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ ¤Ó·˜ ÎÚÈÙÈÎfi˜ ·ÚÈıÌfi˜ ÂÌ‚Ú˘˚ÎÒÓ Î˘ÙÙ¿ÚˆÓ ÚÔ··ÈÙÂ›Ù·È ÁÈ· ÙË Ê˘ÛÈÔÏÔÁÈÎ‹ ·Ó¿Ù˘ÍË ÙÔ˘ ÂÌ‚Ú‡Ô˘ ÌÂÙ¿ ÙËÓ ÂÌÊ‡ÙÂ˘Û‹ ÙÔ˘ (35,36). ∏ ·ÒÏÂÈ· ÂÚÈÛÛfiÙÂÚˆÓ ·fi 60% ÙˆÓ ÂÌ‚Ú˘˚ÎÒÓ Î˘ÙÙ¿ÚˆÓ Ô‰ËÁÂ› ÛÙÔÓ ÂÌ‚Ú˘˚Îfi ı¿Ó·ÙÔ Î·È ÙËÓ ·ÔÚÚfiÊËÛË ÙÔ˘ ÂÌ‚Ú‡Ô˘ (36). ∂ÓÙÔ‡ÙÔÈ˜, Ë ·ÒÏÂÈ· ÏÈÁfiÙÂÚˆÓ ÂÌ‚Ú˘˚ÎÒÓ Î˘ÙÙ¿ÚˆÓ (.¯. 40-45%) ÌÔÚÂ› Ó· Ô‰ËÁ‹ÛÂÈ Â›ÙÂ ÛÂ ·ÔÚÚfiÊËÛË ÙÔ˘ ÂÌ‚Ú‡Ô˘ Â›ÙÂ ÛÙË ‰ËÌÈÔ˘ÚÁ›· Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ. ∏ Â·ÁˆÁ‹ ÙË˜ ·fiÙˆÛË˜ ÛÙÔ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ÌÂÙ¿ ·fi ¤ÎıÂÛË ÛÂ ÙÔÍÈÎÔ‡˜ ·Ú¿ÁÔÓÙÂ˜ ÁÈ· ÌÈÎÚfi ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô‰ËÁÂ› ÛÂ ‰˘ÛÏ·Û›Â˜ ÙÔ˘ ÓˆÙÈ·›Ô˘ ÛˆÏ‹Ó·, ÙˆÓ ¿ÎÚˆÓ Î·È ÙˆÓ ÎÔÈÏÈ·ÎÒÓ ÙÔÈ¯ˆÌ¿ÙˆÓ, ·ÚfiÌÔÈÂ˜ ÌÂ ÙÈ˜ ‰È·Ì·ÚÙ›Â˜ ÙˆÓ ‚ÚÂÊÒÓ ÙˆÓ ‰È·‚ËÙÈÎÒÓ Á˘Ó·ÈÎÒÓ (37-39). º·›ÓÂÙ·È, ÏÔÈfiÓ, fiÙÈ Ô ·˘ÍËÌ¤ÓÔ˜ ‹ ÂÈÙ·¯˘ÓfiÌÂÓÔ˜ ÚÔÁÚ·ÌÌ·ÙÈÛÌ¤ÓÔ˜ Î˘ÙÙ·ÚÈÎfi˜ ı¿Ó·ÙÔ˜ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎÔ‡ ÛÙ·‰›Ô˘ ÙË˜ ·Ó¿Ù˘ÍË˜ Â˘ı‡ÓÂÙ·È ÂÓ Ì¤ÚÂÈ ÁÈ· ÙÈ˜ Û˘ÁÁÂÓÂ›˜ ‰È·Ì·ÚÙ›Â˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘ ÛÙÔÓ ·ÚÚ‡ıÌÈÛÙÔ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË ÙË˜ ÌËÙ¤Ú·˜. ‚) ªÂÙÂÌÊ˘ÙÂ˘ÙÈÎ‹ ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ· ∏ Â›‰Ú·ÛË ÙË˜ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ ÛÙËÓ ÂÌ‚Ú˘ÔÁ¤ÓÂÛË ¤¯ÂÈ ÌÂÏÂÙËıÂ› ÂÎÙÂÓÒ˜ Î·È Î·Ù¿ ¶·È‰È·ÙÚÈÎ‹ 2006;69:409-416

ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎÔ‡ ÛÙ·‰›Ô˘ ·Ó¿Ù˘ÍË˜. ∏ ÂÌÊ‡ÙÂ˘ÛË ÙË˜ ‚Ï·ÛÙÔÎ‡ÛÙË˜ ÛÙÔÓ ¿ÓıÚˆÔ Ï·Ì‚¿ÓÂÈ ¯ÒÚ· ÙË 2Ë Â‚‰ÔÌ¿‰· ÙË˜ Î‡ËÛË˜ (40). ∏ ‰È·‰ÈÎ·Û›· ÙË˜ ·fiÙˆÛË˜ ¤¯ÂÈ Û˘Ó‰ÂıÂ› ¿ÌÂÛ· ÌÂ ÙËÓ ˘ÂÚÁÏ˘Î·ÈÌ›· Î·È ÙËÓ ·Ó¿Ù˘ÍË Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎÔ‡ ÛÙ·‰›Ô˘ ·Ó¿Ù˘ÍË˜. ∞˘Ùfi ·Ô‰›‰ÂÙ·È ÛÂ ÌÂÈˆÌ¤ÓË ¤ÎÊÚ·ÛË ÂÓfi˜ ÛËÌ·ÓÙÈÎÔ‡ ·Ó·Ù˘ÍÈ·ÎÔ‡ ÁÔÓÈ‰›Ô˘ ÂÏ¤Á¯Ô˘, ÙÔ˘ Pax3. ∆Ô Pax3 Â›Ó·È ¤Ó·˜ ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ··Ú·›ÙËÙÔ˜ ÁÈ· ÙË Ê˘ÛÈÔÏÔÁÈÎ‹ ·Ó¿Ù˘ÍË ÙÔ˘ ÂÌ‚Ú˘˚ÎÔ‡ ÓÂ˘ÚÈÎÔ‡ ÛˆÏ‹Ó· (41,42) Î·È Ë ÂÏ·ÙÙˆÌ¤ÓË ¤ÎÊÚ·Û‹ ÙÔ˘ ÛÙ· ÂÈÚ·Ì·Ùfi˙ˆ· Â¿ÁÂÈ ÙË ‰È·‰ÈÎ·Û›· ÙË˜ ·fiÙˆÛË˜ ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÓˆÙÈ·›Ô˘ ÛˆÏ‹Ó· ÙÔ˘ ÂÌ‚Ú‡Ô˘ (4,43,44). √È ÌÂÙ·ÏÏ¿ÍÂÈ˜ ÛÙÔ Pax3 Â˘ı‡ÓÔÓÙ·È ÁÈ· ÙÔÓ Splotch Ê·ÈÓfiÙ˘Ô ÛÙÔ˘˜ ÔÓÙÈÎÔ‡˜ Î·È ÔÈ ÔÌÔ˙˘ÁÒÙÂ˜ ÁÈ· ÙË ÌÂÙ¿ÏÏ·ÍË ·˘Ù‹ ·Ó·Ù‡ÛÛÔ˘Ó ‚Ï¿‚Â˜ ÙÔ˘ ÓˆÙÈ·›Ô˘ ÛˆÏ‹Ó· Î·È ¿ÏÏÂ˜ Û˘ÁÁÂÓÂ›˜ ‰È·Ì·ÚÙ›Â˜ ÌÂ 100% ‰ÈÂÈÛ‰˘ÙÈÎfiÙËÙ· (45-47). ∏ ÔÌ¿‰· ÙÔ˘ Loeken ÚÒÙË Î·Ù¤‰ÂÈÍÂ fiÙÈ Ë ¤ÎÊÚ·ÛË ÙÔ˘ Pax3 ‹Ù·Ó ÂÚ›Ô˘ ÙÚÂÈ˜ ÊÔÚ¤˜ ¯·ÌËÏfiÙÂÚË ÛÙ· ¤Ì‚Ú˘· ‰È·‚ËÙÈÎÒÓ ÔÓÙÈÎÒÓ Û˘ÁÎÚÈÙÈÎ¿ ÌÂ Ù· ¤Ì‚Ú˘· ÌË ‰È·‚ËÙÈÎÒÓ ÔÓÙÈÎÒÓ (4). ∏ ˘fiıÂÛË fiÙÈ Ë ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ· Û˘Ó‰¤ÂÙ·È ÌÂ ÙËÓ ÂÏ·ÙÙˆÌ¤ÓË ¤ÎÊÚ·ÛË ÙÔ˘ Pax3, Û˘ÌÊˆÓÂ› ÌÂ ¿ÏÏ· ·Ú·‰Â›ÁÌ·Ù· ‰˘ÛÌÔÚÊÈÒÓ, ÔÈ ÔÔ›Â˜ ·Ó·Ù‡ÛÛÔÓÙ·È ÛÙÔ˘˜ ·ÔÁfiÓÔ˘˜ ÙˆÓ ‰È·‚ËÙÈÎÒÓ ÔÓÙÈÎÒÓ. ∞˘Ù¤˜ ÔÈ Û˘ÁÁÂÓÂ›˜ ‰È·Ì·ÚÙ›Â˜, Î·È Û˘ÁÎÂÎÚÈÌ¤Ó· Ë ÌÈÎÚÔÁÓ·ı›·, ÔÈ Ì˘ÔÛÎÂÏÂÙÈÎ¤˜ Î·È Î·Ú‰È·Î¤˜ ‰˘ÛÏ·Û›Â˜, ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È Â›ÛË˜ ·fi ‰È·Ù·Ú·¯‹ ÙË˜ ·Ó¿Ù˘ÍË˜ ÈÛÙÒÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È ÌÂ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Pax3 (48). ∆Ô Pax3 ‰Ú· ˆ˜ ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Ô˘ Ú˘ıÌ›˙ÂÈ ÙËÓ ¤ÎÊÚ·ÛË ‰‡Ô ÁÔÓÈ‰›ˆÓ, ÙÔ˘ Cdc46 (37) Î·È ÙÔ˘ Dep1 (38). ∆Ô Cdc46 ÂÌÏ¤ÎÂÙ·È ÛÙË Û‡ÓıÂÛË DNA Î·È ÙË Ú‡ıÌÈÛË ÙÔ˘ Î˘ÙÙ·ÚÈÎÔ‡ Î‡ÎÏÔ˘ (49,50) Î·È ÂÎÊÚ¿˙ÂÙ·È È‰È·›ÙÂÚ· ÛÙÔ ÓÂ˘ÚÈÎfi Û‡ÛÙËÌ· (51). ¶Èı·ÓÔÏÔÁÂ›Ù·È, ÏÔÈfiÓ, fiÙÈ Ë ·˘ÍËÌ¤ÓË ¤ÎÊÚ·ÛË ÙÔ˘ Cdc46 ‰È·‰Ú·Ì·Ù›˙ÂÈ Î¿ÔÈÔ ÚfiÏÔ ÛÙË ‰È·‰ÈÎ·Û›· ÙË˜ ·fiÙˆÛË˜ Ô˘ Ô‰ËÁÂ› ÛÙÈ˜ ‰È·Ù·Ú·¯¤˜ ·Ó¿Ù˘ÍË˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘. ∆Ô Dep1 Û˘Ó‰¤ÂÙ·È, Â›ÛË˜, ÌÂ ÙËÓ ÂÌÊ¿ÓÈÛË Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ (52) ÛÂ ÌË Ú˘ıÌÈ˙fiÌÂÓÔ ‰È·‚‹ÙË ÛÙËÓ Î‡ËÛË Î·È ıÂˆÚÂ›Ù·È fiÙÈ Îˆ‰ÈÎÔÔÈÂ› ¤Ó· ÌÈÎÚfi, ÌË ÌÂÙ·ÊÚ¿ÛÈÌÔ, Ú˘ıÌÈÛÙÈÎfi ÌfiÚÈÔ RNA, Ë ·Ú·ÁˆÁ‹ ÙÔ˘ ÔÔ›Ô˘ ÌÂÈÒÓÂÙ·È ÛÙ· ¤Ì‚Ú˘· ÌÂ ‰È·Ù·Ú·¯¤˜ ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Pax3. H Â›‰Ú·ÛË ÙÔ˘ Pax3 ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Dep1 Î·ı˘ÛÙÂÚÂ› ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÂÎÂ›ÓË ÙÔ˘ Cdc46. °È·

413

AﬁÙˆÛË ÛÙË ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ·

ÙÔÓ ÏfiÁÔ ·˘Ùfi, Èı·ÓÔÏÔÁÂ›Ù·È fiÙÈ ÙÔ Cdc46 Ú˘ıÌ›˙ÂÙ·È ¿ÌÂÛ· ·fi ÙÔ Pax3, ÛÂ ·ÓÙ›ıÂÛË ÌÂ ÙÔ Dep1 Ô˘ Ú˘ıÌ›˙ÂÙ·È ¤ÌÌÂÛ·. ∆· ÁÂÁÔÓfiÙ· Ô˘ Ô‰ËÁÔ‡Ó ·fi ÙËÓ ˘ÂÚÁÏ˘Î·ÈÌ›· ÛÙËÓ ·fiÙˆÛË ÛÙÔ ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ ·Ó¿Ù˘ÍË˜ (19) Û˘ÓÔ„›˙ÔÓÙ·È ÛÙËÓ ∂ÈÎfiÓ· 2. ∞ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ÂÚ¤ıÈÛÌ· Ô˘ ÂÓÂÚÁÔÔÈÂ› ÙÔÓ ·ÔÙˆÙÈÎfi ÌË¯·ÓÈÛÌfi, Ë ÙÂÏÈÎ‹ Ê¿ÛË ÙÔ˘ Î˘ÙÙ·ÚÈÎÔ‡ ı·Ó¿ÙÔ˘ Ì¤Ûˆ ÙË˜ ‰È·‰ÈÎ·Û›·˜ ·˘Ù‹˜ ·ÎÔÏÔ˘ıÂ› ÎÔÈÓ‹ ÂÓ˙˘Ì·ÙÈÎ‹ Ô‰fi. ∞Ú¯ÈÎ¿, ÎÔÈÓfi Ê·ÈÓfiÌÂÓÔ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ·fiÙˆÛË˜ ·ÔÙÂÏÂ› Ë ÏÂÈÙÔ˘ÚÁÈÎ‹ Î·Ù·ÛÙÚÔÊ‹ ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ ÌÂ ÙË ‰ËÌÈÔ˘ÚÁ›· ÏÂÈÙÔ˘ÚÁÈÎÒÓ ÔÒÓ (53). ∞˘Ù¤˜ Â›Ó·È ÂÚÈÔ¯¤˜ ÌÂÙ·Í‡ ÙË˜ ÂÛˆÙÂÚÈÎ‹˜ Î·È ÂÍˆÙÂÚÈÎ‹˜ ÌÂÌ‚Ú¿ÓË˜ ÙÔ˘ ÌÈÙÔ¯ÔÓ‰Ú›Ô˘ Ô˘ ·ÔÙÂÏÔ‡ÓÙ·È ·fi ÔÏ˘ÚˆÙÂ˚ÓÈÎ¿ ÌÔÚÈ·Î¿ Û˘ÌÏ¤ÁÌ·Ù·, Ù· ÔÔ›· ¤¯Ô˘Ó ÙËÓ È‰ÈfiÙËÙ· Ó· ·˘Í¿ÓÔ˘Ó ÙË ÌÈÙÔ¯ÔÓ‰ÚÈ·Î‹ ‰È·ÂÚ·ÙfiÙËÙ· ÁÈ· ‰È¿ÊÔÚÂ˜ “··ÁÔÚÂ˘Ì¤ÓÂ˜” Ô˘Û›Â˜. ∂ÈÏ¤ÔÓ, ÔÈ Î·Û¿ÛÂ˜ ·ÔÙÂÏÔ‡Ó Ì¤ÚÔ˜ ÙË˜ ÎÔÈÓ‹˜ ÙÂÏÈÎ‹˜ ÂÓ˙˘Ì·ÙÈÎ‹˜ Ô‰Ô‡ Î·È Â›Ó·È ÙÂÏÂ›ˆ˜ ··Ú·›ÙËÙÂ˜ ÁÈ· ÙËÓ ·fiÙˆÛË (54). ∏ ÚˆÙÂÔÏ˘ÙÈÎ‹ ‰Ú¿ÛË ÙˆÓ Î·Û·ÛÒÓ ¤¯ÂÈ ˆ˜ ÛÙfi¯Ô ÌÂÁ¿ÏÔ ·ÚÈıÌfi ÚˆÙÂ˚ÓÒÓ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙËÓ ÔÌÔÈfiÛÙ·ÛË, ÙËÓ ÂÈÛÎÂ˘‹ Î·È ÙË ‰È·Ù‹ÚËÛË ÙË˜ Î˘ÙÙ·ÚÈÎ‹˜ ‰ÔÌ‹˜ (55). ÕÏÏÔÈ ·Ú¿ÁÔÓÙÂ˜ Ô˘ ıÂˆÚÔ‡ÓÙ·È fiÙÈ ÂÌÏ¤ÎÔÓÙ·È ÛÙËÓ ·Ó¿Ù˘ÍË ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÂÌ‚Ú˘Ô¿ıÂÈ·˜ Â›Ó·È ÔÈ ·ÁÎÚÂ·ÙÈÎÔ› ÌÂÙ·ÁÚ·ÊÈÎÔ› ·Ú¿ÁÔÓÙÂ˜ Isl-1 Î·È HLXB9, Ô˘ Â›Ó·È ··Ú·›ÙËÙÔÈ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË ÙÔ˘ ·ÁÎÚ¤·ÙÔ˜. ªÂÏ¤ÙÂ˜ ÛÂ ÂÈÚ·Ì·ÙÈÎ¿ ÌÔÓÙ¤Ï· ÔÓÙÈÎÒÓ ¤‰ÂÈÍ·Ó fiÙÈ ÌÂÙ·ÏÏ¿ÍÂÈ˜ ÙˆÓ ·ÁÎÚÂ·ÙÈÎÒÓ ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÚÔÎ·ÏÔ‡Ó ‰˘ÛÏ·Û›Â˜ ÙÔ˘ Ô˘Ú·›Ô˘ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ÛÔÓ‰˘ÏÈÎÔ‡ ÛˆÏ‹Ó·, ·ÚfiÌÔÈÂ˜ ÌÂ ÂÎÂ›ÓÂ˜ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙË ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ· (56,57). ™Ù· ¿Û¯ÔÓÙ· ÙÌ‹Ì·Ù· ‚Ú¤ıËÎÂ ·ıÔÏÔÁÈÎ‹ ¤ÎÊÚ·ÛË ÙÔ˘ Pax-1 Î·È ·˘ÍËÌ¤ÓË ·Ó·ÏÔÁ›· Î˘ÙÙ·ÚÈÎ‹˜ ·fiÙˆÛË˜, Ô˘ ·ÊÔÚÔ‡ÛÂ Î˘Ú›ˆ˜ Ù· ÌÂÛÂÁ¯˘Ì·ÙÈÎ¿ Î‡ÙÙ·Ú· (56). ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿ ˘Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ Ë ÌÂÙ·‚ÔÏÈÎ‹ ‰È·Ù·Ú·¯‹ ÙË˜ ‰È·‚ËÙÈÎ‹˜ Î‡ËÛË˜ ÂËÚÂ¿˙ÂÈ ÙË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÁÎÚÂ·ÙÈÎÒÓ ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, ÔÈ ÔÔ›ÔÈ ÌÂ ÙË ÌÂ ÙË ÛÂÈÚ¿ ÙÔ˘˜ Ô‰ËÁÔ‡Ó ÛÙËÓ ÂÎ‰‹ÏˆÛË ÙÔ˘ ¯·Ú·ÎÙËÚÈÛÙÈÎÔ‡ Ê·ÈÓÔÙ‡Ô˘ ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÂÌ‚Ú˘Ô¿ıÂÈ·˜. ÕÏÏÔÈ ÌË¯·ÓÈÛÌÔ› Ô˘ ¤¯Ô˘Ó ÂÓÔ¯ÔÔÈËıÂ› ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ ÛÙÔ ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎfi ÛÙ¿‰ÈÔ Â›Ó·È Ë ·ÓÂ¿ÚÎÂÈ· ÙˆÓ ÌÂÌ‚Ú·ÓÈÎÒÓ ÏÈÈ‰›ˆÓ (.¯. Ì˘Ô˚ÓÔÛÈÙfiÏË, ·Ú·¯È‰ÔÓÈÎfi ÔÍ‡) (58,59), ÔÈ ·ÏÏ·Á¤˜ ÛÙË Û‡ÓıÂÛË Î·È ÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ

ÀÂÚÁÏ˘Î·ÈÌ›·

ªÂ›ˆÛË ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Pax3

∞‡ÍËÛË ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Cdc46 (ÚÒÈÌÔ ÛÙ¿‰ÈÔ)

ªÂ›ˆÛË ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Dep1 (ﬁ„ÈÌÔ ÛÙ¿‰ÈÔ )

∞fiÙˆÛË ∂ÈÎfiÓ· 2. ∂ÓÂÚÁÔÔ›ËÛË ÙË˜ ·fiÙˆÛË˜ ÛÙË ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎ‹ ‰È·‚ËÙÈÎ‹ ÂÌ‚Ú˘Ô¿ıÂÈ·.

(60,61) Î·È Ë ‰È·Ù·Ú·¯‹ ÙÔ˘ ÂÌ‚Ú˘˚ÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÏfiÁˆ ÙˆÓ ˘„ËÏÒÓ ÂÈ¤‰ˆÓ ÁÏ˘Îfi˙Ë˜ (55,64). ¶Èı·ÓÔÏÔÁÂ›Ù·È fiÙÈ ÔÈ ÙÚÂÈ˜ ·˘ÙÔ› ÌË¯·ÓÈÛÌÔ› Û˘ÁÎÏ›ÓÔ˘Ó ÛÂ ¤Ó·Ó ÎÔÈÓfi ÌÂÙ·‚ÔÏÈÎfi ‰ÚfiÌÔ, Ô˘ Ô‰ËÁÂ› ÙÂÏÈÎ¿ ÛÙËÓ ·‡ÍËÛË ÙˆÓ ÂÏÂ˘ı¤ÚˆÓ ÚÈ˙ÒÓ ÙÔ˘ ÔÍ˘ÁfiÓÔ˘, ÙËÓ ˘ÂÚÔÍÂ›‰ˆÛË ÙˆÓ ÏÈÈ‰›ˆÓ Î·È ÙË ‚Ï¿‚Ë ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ (66,67). ∂ÎÙÈÌ¿Ù·È fiÙÈ Ë ‚Ï¿‚Ë ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ, Ì·˙› ÌÂ ÙÈ˜ ÂÏÂ‡ıÂÚÂ˜ Ú›˙Â˜ ÔÍ˘ÁfiÓÔ˘, ı· ÌÔÚÔ‡ÛÂ Ó· ÂÓÂÚÁÔÔÈ‹ÛÂÈ ÙË ‰È·‰ÈÎ·Û›· ÙË˜ ·fiÙˆÛË˜, ÌÂ ·ÔÙ¤ÏÂÛÌ· ‰È·Ù·Ú·¯¤˜ ÙË˜ ·Ó¿Ù˘ÍË˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘ (65-67). ∂ÓÙÔ‡ÙÔÈ˜, ·˘Ù‹ Ë ˘fiıÂÛË Â›Ó·È ÌfiÓÔ ıÂˆÚËÙÈÎ‹. √È Yang Î·È Û˘Ó. ÂÎÙÈÌÔ‡Ó fiÙÈ ÔÈ ·ÏÏ·Á¤˜ ÛÙÔ Â›Â‰Ô ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ ÌÔÚÔ‡Ó Ó· ·ÓÙÈÛÙÚ·ÊÔ‡Ó ÌÂ ÙËÓ ·ÓÙÈÔÍÂÈ‰ˆÙÈÎ‹ ·ÁˆÁ‹ (68). ¢˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÌË¯·ÓÈÛÌÒÓ ·fiÙˆÛË˜ ÛÙË ‰È·‚ËÙÈÎ‹ Î‡ËÛË ÌÔÚÂ› ·ÎfiÌË Ó· ÚÔÎ‡„ÂÈ ÏfiÁˆ ÙˆÓ ·ÓÔÛÈ·ÎÒÓ ‰È·Ù·Ú·¯ÒÓ, Ô˘ ÔÏÏ¤˜ ÊÔÚ¤˜ Û˘ÓÔ‰Â‡Ô˘Ó ÙË ‰È·‚ËÙÈÎ‹ Î‡ËÛË, fiˆ˜ Â›Ó·È Ë ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ‰ÈÎÙ‡Ô˘ ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ. ¶ÂÈÚ·Ì·ÙÈÎ¤˜ ÌÂÏ¤ÙÂ˜ ÛÂ ‰È·‚ËÙÈÎ¿ ÔÓÙ›ÎÈ· ¤‰ÂÈÍ·Ó fiÙÈ Ë ¯ÔÚ‹ÁËÛË ·ÓÔÛÔ-‰ÈÂÁÂÚÙÒÓ ÛÙË ÌËÙ¤Ú· ÂËÚ¤·ÛÂ ÙË ÏÂÈÙÔ˘ÚÁ›· ÔÏÏÒÓ ·ÔÙˆÙÈÎÒÓ Î·È ·ÓÙÈ·ÔÙˆÙÈÎÒÓ ÁÔÓÈ‰›ˆÓ Î·ıÒ˜ Î·È ÁÔÓÈ‰›ˆÓ Ô˘ Ú˘ıÌ›˙Ô˘Ó ÙÔÓ Î˘ÙÙ·ÚÈÎfi ÔÏÏ·Ï·ÛÈ·ÛÌfi, ÂÏ·ÙÙÒÓÔÓÙ·˜ ÙË Û˘¯ÓfiÙËÙ· Û˘ÁÁÂÓÒÓ ‰˘ÛÏ·ÛÈÒÓ (69). ™˘ÓÔÙÈÎ¿, Ù· ˘¿Ú¯ÔÓÙ· ‰Â‰ÔÌ¤Ó· ‰Â›¯ÓÔ˘Ó fiÙÈ, ·Ó Î·È ÔÈ ÌË¯·ÓÈÛÌÔ› ‰ËÌÈÔ˘ÚÁ›·˜ Û˘ÁÁÂÓÒÓ ‰˘ÛÏ·ÛÈÒÓ ÛÙË ‰È·‚ËÙÈÎ‹ Î‡ËÛË ‰È·Ê¤ÚÔ˘Ó ÌÂÙ·Í‡ ÚÔÂÌÊ˘ÙÂ˘ÙÈÎÔ‡ Î·È ÌÂÙÂÌÊ˘ÙÂ˘ÙÈÎÔ‡ ÛÙ·‰›Ô˘ ·Ó¿Ù˘ÍË˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘, Ë ‚·ÛÈÎ‹ ·ıÔÁ¤ÓÂÈ· Â›Ó·È ›‰È·: Ë ˘ÂÚÁÏ˘Î·ÈÌ›· ÙË˜ ÌËÙ¤Ú·˜ ‰ÈÂÁÂ›ÚÂÈ ÙÔÓ ÚÔÁÚ·ÌÌ·ÙÈÛÌ¤ÓÔ Î˘ÙÙ·ÚÈÎfi ı¿Ó·ÙÔ ÛÙÔ ·Ó·Ù˘ÛÛfiÌÂÓÔ ¤Ì‚Ú˘Ô, ÌÂ ·ÔÙ¤ÏÂÛÌ· ‰˘ÛÏ·Û›Â˜ ‹ ·Ô‚ÔÏ‹ ÙÔ˘ ÂÌ‚Ú‡Ô˘ (19). ¶·È‰È·ÙÚÈÎ‹ 2006;69:409-416

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417

√ Û˘Ó‰˘·ÛÌfi˜ ÂÈÛÓÂfiÌÂÓˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ Î·È ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÛÙË ıÂÚ·Â›· ÙÔ˘ ·È‰ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ ª. B. ∞ÓıÚ·ÎfiÔ˘ÏÔ˜1, ∫. ¡. ¶Ú›ÊÙË˜2

¶ÂÚ›ÏË„Ë: ™‡ÌÊˆÓ· ÌÂ ÙÈ˜ ÔÌÔÊˆÓ›Â˜ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ¿ÛıÌ·ÙÔ˜, Ô Û˘Ó‰˘·ÛÌfi˜ ÂÈÛÓÂfiÌÂÓˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ (∂ÈÛ∫™) Î·È ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ·ÔÙÂÏÂ› ÙË ıÂÚ·Â›· ÂÎÏÔÁ‹˜ ÛÙÔ Ì¤ÙÚÈÔ Î·È ÛÔ‚·Úfi (Â›ÌÔÓÔ) ¿ÛıÌ·, ÂÓÒ Ë ÚÔÛı‹ÎË ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ Û˘ÓÈÛÙ¿Ù·È ÛÙÔ ‹ÈÔ Â›ÌÔÓÔ ¿ÛıÌ· Ô˘ ‰ÂÓ ÂÏ¤Á¯ÂÙ·È ÌÂ ¯·ÌËÏ¤˜ ‰fiÛÂÈ˜ ∂ÈÛ∫™, ÙfiÛÔ ÛÂ ÂÓ‹ÏÈÎÂ˜ fiÛÔ Î·È ÛÂ ·È‰È¿, È‰›ˆ˜ ÛÂ ÂÎÂ›Ó· ËÏÈÎ›·˜ ÌÂÁ·Ï‡ÙÂÚË˜ ÙˆÓ 5 ÂÙÒÓ. ∏ Û˘Ó‰˘·˙fiÌÂÓË ıÂÚ·Â›· ‚·Û›˙ÂÙ·È ÛÙË Û˘ÌÏËÚˆÌ·ÙÈÎ‹ Ê·ÚÌ·ÎÂ˘ÙÈÎ‹ ‰Ú¿ÛË ÙˆÓ ∂ÈÛ∫™ (·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë˜) Î·È ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ (‚ÚÔÁ¯Ô‰È·ÛÙÔÏ‹, ‚ÚÔÁ¯ÔÚÔÛÙ·Û›·), ·ÏÏ¿ Î·È ÛÙË Û˘Ó¤ÚÁÂÈ· ÙË˜ ‰Ú¿ÛË˜ ÙˆÓ ‰‡Ô ‰È·ÊÔÚÂÙÈÎÒÓ Î·ÙËÁÔÚÈÒÓ ·ÓÙÈ·ÛıÌ·ÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÂ Î˘ÙÙ·ÚÈÎfi Â›Â‰Ô (Â˘fi‰ˆÛË ÙË˜ ¤ÎÊÚ·ÛË˜ ÙˆÓ ‚2-˘Ô‰Ô¯¤ˆÓ ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ Î˘ÙÙ¿ÚˆÓ ·fi Ù· ∂ÈÛ∫™ Î·È ÂÓ›Û¯˘ÛË ÙˆÓ ÂÓ‰ÔÎ˘ÙÙ¿ÚÈˆÓ ÌË¯·ÓÈÛÌÒÓ ‰Ú¿ÛË˜ ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ Ì¤Ûˆ ‰È¤ÁÂÚÛË˜ ÙˆÓ ·‰ÚÂÓÂÚÁÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ ·fi ÙÔ˘˜ ‚2-·ÁˆÓÈÛÙ¤˜). ∂ÎÙÂÙ·Ì¤ÓË ÎÏÈÓÈÎ‹ ¤ÚÂ˘Ó· ÛÂ ÂÓ‹ÏÈÎÂ˜ ·ÛıÌ·ÙÈÎÔ‡˜ ¤¯ÂÈ ‰Â›ÍÂÈ, ¤Ú·Ó Î¿ıÂ ·ÌÊÈ‚ÔÏ›·˜, ÙËÓ ˘ÂÚÔ¯‹ ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙÒÓ Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÌÔÓÔıÂÚ·Â›· ÌÂ ÙËÓ ›‰È· ‹ Î·È ‰ÈÏ¿ÛÈ· ‰fiÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰Ô‡˜. ™ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË Á›ÓÂÙ·È ·Ó·ÊÔÚ¿ ÛÙÈ˜ ÂÚÈÔÚÈÛÌ¤ÓÂ˜ ·ÚÈıÌËÙÈÎ¿ ·È‰È·ÙÚÈÎ¤˜ ÌÂÏ¤ÙÂ˜ Ô˘ ‰ÈÂÚÂ˘ÓÔ‡Ó ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È ÙËÓ ·ÛÊ¿ÏÂÈ· ÙË˜ Û˘Ó‰˘·˙fiÌÂÓË˜ ıÂÚ·Â›·˜ ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÙË ¯ÔÚ‹ÁËÛË ›‰È·˜ ‹ ‰ÈÏ¿ÛÈ·˜ ‰fiÛË˜ ∂ÈÛ∫™. ™ÙËÓ ÏÂÈÔÓfiÙËÙ¿ ÙÔ˘˜ - Î·È ÔÈ ÌÂÏ¤ÙÂ˜ ·˘Ù¤˜ - ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ ˘ÂÚÔ¯‹ ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜. ∂›ÛË˜, Û˘˙ËÙÔ‡ÓÙ·È Ù· ÔÏ‡ ÂÓ‰È·Ê¤ÚÔÓÙ· Î·È ÂÏÈ‰ÔÊfiÚ· ·ÔÙÂÏ¤ÛÌ·Ù· ‰‡Ô ÚfiÛÊ·ÙˆÓ ÌÂÁ¿ÏˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ ÛÂ ÂÓ‹ÏÈÎÂ˜ ·ÛıÂÓÂ›˜ Ô˘ ‰ÈÂÚÂ˘ÓÔ‡Ó ÙË ‰˘Ó·ÙfiÙËÙ· “È‰·ÓÈÎÔ‡” ÂÏ¤Á¯Ô˘ ÙÔ˘ ¿ÛıÌ·ÙÔ˜ ÌÂ Û˘Á¯ÔÚ‹ÁËÛË (ÌÂ ÂÓÈ·›· Û˘ÛÎÂ˘‹) ÙˆÓ Û˘Ó‰˘·ÛÌÒÓ Û·ÏÌÂÙÂÚfiÏË˜/ÊÏÔ˘ÙÈÎ·˙fiÓË˜ Î·È ‚Ô˘‰ÂÛÔÓ›‰Ë˜/ÊÔÚÌÔÙÂÚfiÏË˜.

1 ¶·È‰ÔÓÂ˘ÌÔÓÔÏÔÁÈÎ‹ ªÔÓ¿‰·, ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ 2 ∞ÏÏÂÚÁÈÔÏÔÁÈÎfi ∆Ì‹Ì·, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ¶ÂÓÙ¤ÏË˜, ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ªÈ¯¿ÏË˜ ∞ÓıÚ·ÎfiÔ˘ÏÔ˜ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ ∆.∫. 265 04, ƒ›Ô, ¶¿ÙÚ· ∂-mail: manthra@otenet.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 04-04-2006 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 19-09-2006

§¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ÕÛıÌ·, ÂÈÛÓÂﬁÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹, ‚2-·ÁˆÓÈÛÙ¤˜ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜, Û˘Ó‰˘·ÛÌﬁ˜(Ô›).

Combination therapy with inhaled corticosteroids and long-acting ‚2-agonists in childhood asthma M. B. Anthracopoulos1, K. N. Priftis2

Abstract: According to current guidelines for the management of asthma, the combination of inhaled corticosteroids (iCS) and long acting ‚2-agonists (LABA) is recommended in moderate and severe (persistent) asthma, and LABA constitute add-on treatment in mild persistent asthma that cannot be controlled by low-dose iCS, especially in adults and children over 5 years of age. Such combination treatment is based on sound scientific evidence of the complementary pharmacological effects of iCS (antiinflammatory) and LABA (bronchodilation, bronchoprotection), as well as their synergistic effect at the cellular level (iCS induction of the expression of ‚2-agonists on the cellular membrane and amplification of intracellular mechanisms of action of corticosteroids by agonist stimulation of ‚2-adrenoreceptors). Extensive clinical research in adults has proved beyond doubt that combination therapy with iCS and LABA is more effective than iCS monotherapy with an equal or double dose of corticosteroids. This review summarizes the findings of the relatively small number of paediatric studies investigating the effectiveness and safety of combination therapy as compared to administration of the same or a double dose of iCS therapy. Most of these studies, like the adult data, support the superiority of iCS/LABA combination over iCS monotherapy. The intriguing and hopeful results of two recent large clinical trials that investigated the feasibility of improved, or even total, asthma control in adult patients

1 Unit of Paediatric Pulmonology, Paediatric Clinic of the University of Patras 2 Department of Allergology, Penteli Children’s Hospital, Athens Correspondence: Michael Anthracopoulos Paediatric Clinic of the University of Patras 265 04, Rio, Patra ∂-mail: manthra@otenet.gr Date of submission: 04-04-2006 Date of approval: 19-09-2006

¶·È‰È·ÙÚÈÎ‹ 2006;69:417-424

418

ª. B. ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜, ∫. ¡. ¶Ú›ÊÙË˜

using novel management protocols (i.e., salmeterol/fluticasone and the budesonide/formoterol combinations) are also discussed.

Key words: Asthma, inhaled corticosteroids, long-acting ‚2-agonists, combination(s).

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ ∂ÈÛ∫™ ∂ÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ cPLA2 ∫˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎ‹ ÊˆÛÊÔÏÈ¿ÛË ∞2 FEV1 µ›·È· ÂÎÓÂfiÌÂÓÔ˜ fiÁÎÔ˜ ÛÙÔ ÚÒÙÔ ‰Â˘ÙÂÚfiÏÂÙÔ GRE ∞ÏÏËÏÔ˘¯›Â˜ ÁÔÓÈ‰›ˆÓ ·ÓÙ·fiÎÚÈÛË˜ ÛÙ· ÁÏ˘ÎÔÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ IL-5 πÓÙÂÚÏÂ˘Î›ÓË-5 iCS ∂ÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ LABA ‚2-·ÁˆÓÈÛÙ‹˜(-¤˜) Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ MAPK ¶ÚˆÙÂ˚ÓÈÎ‹(-¤˜) ÎÈÓ¿ÛË(-Â˜) ÂÓÂÚÁÔÔÈÔ‡ÌÂÓË(-Â˜) ÌÂ ÌÈÙÔÁfiÓÔ PAF ¶·Ú¿ÁÔÓÙ·˜ ÂÓÂÚÁÔÔ›ËÛË˜ ·ÈÌÔÂÙ·Ï›ˆÓ ¢fiÛË ÚfiÎÏËÛË˜ ÙÒÛË˜ ÙÔ˘ FEV1 Î·Ù¿ PD20 20% PEF ª¤ÁÈÛÙË ÂÎÓÂ˘ÛÙÈÎ‹ ÚÔ‹ PKA ¶ÚˆÙÂ˚ÓÈÎ‹ ÎÈÓ¿ÛË A

∂ÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ (∂ÈÛ∫™) Î·È ‚2-·ÁˆÓÈÛÙ¤˜ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ∏ Û˘ÓÂÈ‰ËÙÔÔ›ËÛË fiÙÈ ÙÔ ¿ÛıÌ· ·ÔÙÂÏÂ› ¯ÚfiÓÈ· ÊÏÂÁÌÔÓÒ‰Ë ÓfiÛÔ ÙˆÓ ·ÂÚ·ÁˆÁÒÓ Ô‰‹ÁËÛÂ ÛÙËÓ Â˘Ú‡Ù·ÙË ¯Ú‹ÛË ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ (∂ÈÛ∫™) ˆ˜ ÙˆÓ Ï¤ÔÓ ·ÔÙÂÏÂÛÌ·ÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ÙË˜ ÓfiÛÔ˘. ¶Ú¿ÁÌ·ÙÈ, ÛÙÔ Ù¤ÏÔ˜ ÙË˜ ‰ÂÎ·ÂÙ›·˜ ÙÔ˘ ’80 Î·È ÛÙÈ˜ ·Ú¯¤˜ ÙË˜ ÂfiÌÂÓË˜, ÔÈ ÓÂÔÛ˘ÛÙ·ıÂ›ÛÂ˜ ÙfiÙÂ ÔÌÔÊˆÓ›Â˜ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ¿ÛıÌ·ÙÔ˜ Û˘ÓÈÛÙÔ‡Û·Ó ÙËÓ ÚÔÔ‰Â˘ÙÈÎ‹ ·‡ÍËÛË ÙË˜ ËÌÂÚ‹ÛÈ·˜ ‰fiÛË˜ ÙˆÓ ∂ÈÛ∫™, ÚÔÎÂÈÌ¤ÓÔ˘ Ó· ÂÈÙÂ˘¯ıÂ› Ô ¤ÏÂÁ¯Ô˜ ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Î·È Ë ‚¤ÏÙÈÛÙË ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ·ÛıÌ·ÙÈÎÔ‡ ·ÛıÂÓÔ‡˜ (2). ™˘Á¯ÚfiÓˆ˜, Ê·ÚÌ·ÎÔÏÔÁÈÎ¤˜ ÌÂÏ¤ÙÂ˜ Î·Ù¤ÛÙËÛ·Ó Ê·ÓÂÚfi fiÙÈ Ù· ∂ÈÛ∫™ ÂÈÙ˘Á¯¿ÓÔ˘Ó ÙÔ Ì¤ÁÈÛÙÔ ÙË˜ ‰Ú¿ÛË˜ ÙÔ˘˜ ÛÂ Û¯ÂÙÈÎ¿ ¯·ÌËÏ¤˜ ‰fiÛÂÈ˜, Ô˘ ¿ÓÙˆ˜ ‰ÂÓ ˘ÂÚ‚·›ÓÔ˘Ó Ù· 1000 Ìg ÂÚ›Ô˘ ËÌÂÚËÛ›ˆ˜ (1). √È ÂÈÛÓÂfiÌÂÓÔÈ ‚2-·ÁˆÓÈÛÙ¤˜ ·ÔÙÂÏÔ‡Ó Ù· ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚ· ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ¿ Ê¿ÚÌ·Î· ÛÙË ıÂÚ·Â›· ÙÔ˘ ¿ÛıÌ·ÙÔ˜ (2) Î·È ‰È·ÎÚ›ÓÔÓÙ·È ÛÙÔ˘˜ ‚Ú·¯Â›·˜ (Ì¤ÁÈÛÙË ‰È¿ÚÎÂÈ· 4-6 ÒÚÂ˜) Î·È ÛÙÔ˘˜ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ (Ì¤ÁÈÛÙË ‰È¿ÚÎÂÈ· ÂÚ›Ô˘ 12 ÒÚÂ˜). √È ÂÎÏÂÎÙÈÎÔ› ‚2-·ÁˆÓÈÛÙ¤˜ ‚Ú·¯Â›·˜ ‰Ú¿ÛË˜ (Û·Ï‚Ô˘Ù·ÌfiÏË, ÙÂÚ‚Ô˘Ù·Ï›ÓË) ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙÔ ¶·È‰È·ÙÚÈÎ‹ 2006;69:417-424

¿ÛıÌ· ˆ˜ ·Ó·ÎÔ˘ÊÈÛÙÈÎ‹ “Î·Ù’ Â›ÎÏËÛÈÓ” ·ÁˆÁ‹, ‰ËÏ·‰‹ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ÙË˜ ÓfiÛÔ˘. ∂›ÛË˜, ÚÔÙÂ›ÓÔÓÙ·È ˆ˜ ‚ÚÔÁ¯ÔÚÔÛÙ·Û›· Ï›Á· ÏÂÙ¿ ÚÈÓ ·fi ÙËÓ ¿ÛÎËÛË ÛÂ ·ÛıÂÓÂ›˜ ÌÂ “¿ÛıÌ· ÌÂÙ¿ ·fi ¿ÛÎËÛË” (2). ∞ÓÙÈı¤Ùˆ˜, ÔÈ ‚2-·ÁˆÓÈÛÙ¤˜ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ (Û·ÏÌÂÙÂÚfiÏË: ‚Ú·‰Â›·˜ ¤Ó·ÚÍË˜ ‰Ú¿ÛË˜, ÊÔÚÌÔÙÂÚfiÏË: Ù·¯Â›·˜ ¤Ó·ÚÍË˜ ‰Ú¿ÛË˜) ÂÈÛ‹¯ıËÛ·Ó ÛÙËÓ ÎÏÈÓÈÎ‹ Ú¿ÍË ·fi Ù· Ì¤Û· ÙË˜ ‰ÂÎ·ÂÙ›·˜ ÙÔ˘ ’90 Î·È ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È, Û‡ÌÊˆÓ· ÌÂ ÙÈ˜ Ï¤ÔÓ ÚfiÛÊ·ÙÂ˜ ÔÌÔÊˆÓ›Â˜, ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ¿ÛıÌ·ÙÔ˜ ˆ˜ Ú˘ıÌÈÛÙÈÎ‹ “Ì·ÎÚÔ¯ÚfiÓÈ·” ·ÁˆÁ‹ ÛÂ Û˘Ó‰˘·ÛÌfi ÌÂ Ù· ∂ÈÛ∫™ (3-5). ™‡ÌÊˆÓ· ÌÂ ÙËÓ ÙÚ¤¯Ô˘Û· Ú·ÎÙÈÎ‹ ·ÔÙÂÏÔ‡Ó ÙË ıÂÚ·Â›· ÂÎÏÔÁ‹˜ ÛÙÔ Ì¤ÙÚÈÔ Î·È ÛÔ‚·Úfi (Â›ÌÔÓÔ) ¿ÛıÌ· ·È‰ÈÒÓ ËÏÈÎ›·˜ ÌÂÁ·Ï‡ÙÂÚË˜ ÙˆÓ 5 ÂÙÒÓ Î·È Û˘ÓÈÛÙ¿Ù·È Ë ÚÔÛı‹ÎË ÙÔ˘˜ ÛÂ ¯·ÌËÏ‹ ‰fiÛË ∂ÈÛ∫™, ˆ˜ ÚÒÙË ıÂÚ·Â˘ÙÈÎ‹ ÂÈÏÔÁ‹, ÛÙÔ ‹ÈÔ Â›ÌÔÓÔ ¿ÛıÌ· Ô˘ ‰ÂÓ ÂÏ¤Á¯ÂÙ·È ÌÂ ÙÈ˜ ¯·ÌËÏ¤˜ ·˘Ù¤˜ ‰fiÛÂÈ˜ (2,6-8). ™Â ·È‰È¿ ËÏÈÎ›·˜ ÌÈÎÚfiÙÂÚË˜ ÙˆÓ 5 ÂÙÒÓ, Ô Û˘Ó‰˘·ÛÌfi˜ ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ Î·È ¯·ÌËÏ‹˜ ‰fiÛË˜ ∂ÈÛ∫™ ·ÔÙÂÏÂ› ÙË ıÂÚ·Â›· ÂÎÏÔÁ‹˜ ÛÙÔ Ì¤ÙÚÈÔ (¯ÚfiÓÈÔ) ¿ÛıÌ· Û‡ÌÊˆÓ· ÌÂ ÙËÓ ∞ÌÂÚÈÎ·ÓÈÎ‹ √ÌÔÊˆÓ›· (6) Î·È ÂÓ·ÏÏ·ÎÙÈÎ‹ ıÂÚ·Â˘ÙÈÎ‹ ÂÈÏÔÁ‹ Û‡ÌÊˆÓ· ÌÂ ÙË ¢ÈÂıÓ‹ (ıÂÚ·Â›· ÂÎÏÔÁ‹˜: Ì¤ÙÚÈ· ‰fiÛË ∂ÈÛ∫™) (2) Î·È ÙË µÚÂÙ·ÓÈÎ‹ √ÌÔÊˆÓ›· (ıÂÚ·Â›· ÂÎÏÔÁ‹˜: Û˘Ó‰˘·ÛÌfi˜ ·ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎÔ‡ Î·È ¯·ÌËÏ‹˜ ‰fiÛË˜ ∂ÈÛ∫™) (7). ™ÙË Û˘Ó¤¯ÂÈ· ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÂÚÈÏËÙÈÎ¿ Ë Ê·ÚÌ·ÎÂ˘ÙÈÎ‹ ‚¿ÛË ÙË˜ ·ıÚÔÈÛÙÈÎ‹˜ Î·È Ë ÌÔÚÈ·Î‹ ‚¿ÛË ÙË˜ Û˘ÓÂÚÁÈÎ‹˜ ‰Ú¿ÛË˜ ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ Î·È ·Ú·Ù›ıÂÓÙ·È Ù· Î˘ÚÈfiÙÂÚ· ÎÏÈÓÈÎ¿ ‰Â‰ÔÌ¤Ó· ÁÈ· ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙË˜ Û˘Á¯ÔÚ‹ÁËÛ‹˜ ÙÔ˘˜ ÛÂ ·ÛıÌ·ÙÈÎ¿ ·È‰È¿. ∞ıÚÔÈÛÙÈÎ‹ Î·È Û˘ÓÂÚÁÈÎ‹ ‰Ú¿ÛË ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙÒÓ ∏ Û˘Ì‚·ÙÈÎ‹ ÁÓÒÛË ÁÈ· ÙÔÓ ·ÓÙÈ·ÛıÌ·ÙÈÎfi ÚfiÏÔ ÙˆÓ ∂ÈÛ∫™ Î·È ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ·Ó·ÁÓˆÚ›˙ÂÈ ÛÙÈ˜ ‰‡Ô ·˘Ù¤˜ Î·ÙËÁÔÚ›Â˜ Ô˘ÛÈÒÓ ·ÔÏ‡Ùˆ˜ ‰È·ÎÚÈÙ¤˜ Ê·ÚÌ·ÎÂ˘ÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜: ·) ∆· ∂ÈÛ∫™ ÂÈ‰ÚÔ‡Ó ÛÂ Ì›· ÔÈÎÈÏ›· Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·È ÌÂÛÔÏ·‚ËÙÒÓ, ÌÂ

419

∂ÈÛÓÂﬁÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ Î·È ‚2-·ÁˆÓÈÛÙ¤˜ ÛÙÔ ·È‰ÈÎﬁ ¿ÛıÌ·

·ÔÙ¤ÏÂÛÌ· ÙËÓ Î·Ù·ÛÙÔÏ‹ ÙË˜ ¯ÚfiÓÈ·˜ ÊÏÂÁÌÔÓ‹˜ ÙˆÓ ·ÂÚ·ÁˆÁÒÓ Î·È ÙËÓ ÂÏ¿ÙÙˆÛË ÙË˜ ‚ÚÔÁ¯ÈÎ‹˜ ˘ÂÚ··ÓÙËÙÈÎfiÙËÙ·˜. ‚) √È ‚2·ÁˆÓÈÛÙ¤˜ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ‰ÈÂÁÂ›ÚÔ˘Ó ÙÔ˘˜ ‚2˘Ô‰Ô¯Â›˜ ÙˆÓ ÏÂ›ˆÓ Ì˘˚ÎÒÓ ÈÓÒÓ ÛÙÔ ÙÔ›¯ˆÌ· ÙˆÓ ·ÂÚ·ÁˆÁÒÓ, ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ¿ÛÎËÛË ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ‹˜ ‰Ú¿ÛË˜ Â› 12ˆÚÔ ÂÚ›Ô˘ (∂ÈÎfiÓ· 1·) (9). ∞˘Í·ÓfiÌÂÓÔ˜ ·ÚÈıÌfi˜ ÌÂÏÂÙÒÓ ÛÂ Â›Â‰Ô ‚·ÛÈÎ‹˜ ¤ÚÂ˘Ó·˜ ¤¯ÂÈ ‰Â›ÍÂÈ fiÙÈ ÔÈ ‚2-·ÁˆÓÈÛÙ¤˜, ¤Ú·Ó ÙË˜ ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ‹˜, ·ÛÎÔ‡Ó Î·È ‚ÚÔÁ¯ÔÚÔÛÙ·ÙÂ˘ÙÈÎ‹ ‰Ú¿ÛË. ∂È‰ÈÎfiÙÂÚ·, ¤¯ÂÈ ·Ô‰ÂÈ¯ıÂ› fiÙÈ: ·) ÚÔÎ·ÏÔ‡Ó ·Ó·ÛÙÔÏ‹ ÙË˜ ·ÔÎÔÎÎ›ˆÛË˜ ÙˆÓ Ì·ÛÙÔÎ˘ÙÙ¿ÚˆÓ Ô˘ ·ÔÙÂÏÂ› ‚·ÛÈÎfi ÌË¯·ÓÈÛÌfi ÙË˜ ¿ÌÂÛË˜ ·ÓÙ›‰Ú·ÛË˜ ÛÙÔ ¿ÛıÌ·, ‚) ÂÌÔ‰›˙Ô˘Ó ÙËÓ ÂÍ›‰ÚˆÛË ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ Ô˘ Ô‰ËÁÂ› ÛÂ Ô›‰ËÌ· ÙˆÓ ·ÂÚ·ÁˆÁÒÓ Î·È Á) Â›Ó·È Èı·Ófi Ó· ÂÏ·ÙÙÒÓÔ˘Ó ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ·ÈÛıËÙÈÎÒÓ ÓÂ˘ÚÈÎÒÓ ÈÓÒÓ ÛÙÔ˘˜ ‚ÚfiÁ¯Ô˘˜ (∂ÈÎfiÓ· 1‚) (10). ∂ÈÏ¤ÔÓ, Ù· ∂ÈÛ∫™ Â˘Ô‰ÒÓÔ˘Ó ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ‚2-˘Ô‰Ô¯¤ˆÓ ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ì¤Ûˆ ·‡ÍËÛË˜ ÙË˜ ÌÂÙ·ÁÚ·Ê‹˜ ÙˆÓ ˘Â‡ı˘ÓˆÓ ÁÔÓÈ‰›ˆÓ. ∏ ‰Ú¿ÛË ÙÔ˘˜ ·˘Ù‹ Ì¿ÏÏÔÓ ÛÙÂÚÂ›Ù·È ÎÏÈÓÈÎ‹˜ ÛËÌ·Û›·˜ ˆ˜ ÚÔ˜ ÙÔ ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎfi ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ, ÂÓ fi„ÂÈ ÙÔ˘ ÙÂÚ¿ÛÙÈÔ˘ ·Ôı¤Ì·ÙÔ˜ ‚2˘Ô‰Ô¯¤ˆÓ ÛÙËÓ Î˘ÙÙ·ÚÈÎ‹ ÌÂÌ‚Ú¿ÓË ÙˆÓ ÏÂ›ˆÓ Ì˘˚ÎÒÓ ÈÓÒÓ Î·È ÂÂÈ‰‹ Ë ÂÎ‰‹ÏˆÛË ·ÓÔ¯‹˜ ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Â‡ÎÔÏ· ÛÙËÓ ÎÏÈÓÈÎ‹ Ú·ÎÙÈÎ‹ ÌÂ ·‡ÍËÛË ÙË˜ ‰fiÛË˜ ÙÔ˘ ‚2-·ÁˆÓÈÛÙ‹. øÛÙfiÛÔ, ÌÔÚÂ› Ó· ·Ô‚Â› ÎÏÈÓÈÎ¿ ÎÚ›ÛÈÌË ÛÂ Î‡ÙÙ·Ú· Ô˘ ‰È·ı¤ÙÔ˘Ó ÂÚÈÔÚÈÛÌ¤ÓÔ ·ÚÈıÌfi ‚2-˘Ô‰Ô¯¤ˆÓ - fiˆ˜ Â›Ó·È Ù· Ì·ÛÙÔÎ‡ÙÙ·Ú· - Î·È ÂÌÏ¤ÎÔÓÙ·È ¿ÌÂÛ· ÛÙÔÓ ÌË¯·ÓÈÛÌfi ‰È·Ù‹ÚËÛË˜ ÙË˜ ‚ÚÔÁ¯ÔÚÔÛÙ·ÙÂ˘ÙÈÎ‹˜ ÙÔ˘˜ ‰Ú¿ÛË˜ (10). √È ‚2-·ÁˆÓÈÛÙ¤˜ Ê·›ÓÂÙ·È fiÙÈ ÂÓÈÛ¯‡Ô˘Ó ÙÔ˘˜ ÂÓ‰ÔÎ˘ÙÙ¿ÚÈÔ˘˜ ÌË¯·ÓÈÛÌÔ‡˜ ‰Ú¿ÛË˜ ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ ÌÂ ÙËÓ ÚÔ·ÁˆÁ‹ ÙË˜ ÂÁÎ·Ù¿ÛÙ·ÛË˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ ÛÙÔÓ ˘Ú‹Ó· ÙÔ˘ Î˘ÙÙ¿ÚÔ˘ ÛÙÈ˜ ı¤ÛÂÈ˜ GRE (·ÏÏËÏÔ˘¯›Â˜ ÁÔÓÈ‰›ˆÓ ·ÓÙ·fiÎÚÈÛË˜ ÛÙ· ÁÏ˘ÎÔÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹) (10). ™ÙËÓ ∂ÈÎfiÓ· 2 Ê·›ÓÂÙ·È Û¯ËÌ·ÙÈÎ¿ Ë ·ÏÏËÏÂ›‰Ú·ÛË ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ ÌÂ ÙÔ˘˜ ‚2·ÁˆÓÈÛÙ¤˜ ÛÂ Î˘ÙÙ·ÚÈÎfi Â›Â‰Ô. ÕÏÏË ‰Ú¿ÛË ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ, Èı·ÓfiÓ ÂÈÎÔ˘ÚÈÎ‹ ÙˆÓ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ È‰ÈÔÙ‹ÙˆÓ ÙˆÓ ∂ÈÛ∫™, Â›Ó·È Ë ÌÂÙÂÁÎ·Ù¿ÛÙ·ÛË (translocation) ÙË˜ Î˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎ‹˜ ÊˆÛÊÔÏÈ¿ÛË˜ ∞2 (cPLA2) ÛÙËÓ ˘ÚËÓÈÎ‹ ÌÂÌ‚Ú¿ÓË. ∏ ÂÓÂÚÁÔÔ›ËÛË ÙË˜ cPLA2 Ô‰ËÁÂ› ÛÙËÓ ·˘ÍËÌ¤ÓË ÚÔÛÎfiÏÏË-

∞ÓÙÈÁﬁÓÔ ª·ÎÚÔÊ¿Á· ∏ˆÛÈÓﬁÊÈÏ·

ÀÂÚ··ÓÙËÙÈÎﬁÙËÙ· ·ÂÚ·ÁˆÁÒÓ ∆-ÏÂÌÊÔÎ‡ÙÙ·Ú· πﬁ˜?

∫ÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ ‚

‚2-·ÁˆÓÈÛÙ¤˜

πÔ›? ∞‰ÂÓÔÛ›ÓË ÕÛÎËÛË ÀÁÚ·Û›·

µÚÔÁ¯ÔÛ‡Û·ÛË ∂ÓÂÚÁÔÔ›ËÛË ∞ÔÎÔÎÎ›ˆÛË ∂Í·ÁÁÂ›ˆÛË ·ÈÛıËÙ‹ÚÈˆÓ ∞ÓÙÈÁﬁÓÔ Ì·ÛÔÎ˘ÙÙ¿ÚˆÓ Ï¿ÛÌ·ÙÔ˜ ÓÂ‡ÚˆÓ ¢Ú¿ÛË:

- µÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ‹ - µÚÔÁ¯ÔÚÔÛÙ·ÙÂ˘ÙÈÎ‹ - (∞ÓÙÈÊÏÂÁÌÔÓÒ‰Ë˜;)

∂ÈÎﬁÓ· 1. ∞ıÚÔÈÛÙÈÎ‹ ‰Ú¿ÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ Î·È ‚2·ÁˆÓÈÛÙÒÓ ÛÙÔ ¿ÛıÌ·: ·) ∏ ·Ó·ÛÙ·ÏÙÈÎ‹ ‰Ú¿ÛË ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ ÛÙ· Î‡ÙÙ·Ú· Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ÛıÌ·ÙÈÎ‹ ÊÏÂÁÌÔÓ‹. ‚) µÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ‹ Î·È ‚ÚÔÁ¯ÔÚÔÛÙ·ÙÂ˘ÙÈÎ‹ ‰Ú¿ÛË ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ [·ﬁ Barnes PJ (10), ÙÚÔÔÔÈËÌ¤ÓÔ].

ÛË ÙˆÓ ËˆÛÈÓÔÊ›ÏˆÓ, ÙﬁÛÔ Ì¤Ûˆ ÙÔ˘ PAF (·Ú¿ÁÔÓÙ·˜ ÂÓÂÚÁÔÔ›ËÛË˜ ·ÈÌÔÂÙ·Ï›ˆÓ) ﬁÛÔ Î·È Ì¤Ûˆ ‰È¤ÁÂÚÛË˜ ÙË˜ ·Ú·ÁˆÁ‹˜ IL-5 (ÈÓÙÂÚÏÂ˘Î›ÓË-5) (11).

‚2 -·ÁˆÓÈÛÙ‹˜

∫ÔÚÙÈÎÔÛÙÂÚÔÂÈ‰¤˜

‚2-˘Ô‰Ô¯¤·˜

cyclic AMP

+ ÀÔ‰Ô¯¤·˜ ∫™

ÚˆÙÂ˝ÓË

PKA

MAPK

¶˘Ú‹Ó·˜

GRE

mRNA

°ÔÓ›‰ÈÔ ·¿ÓÙËÛË˜ ∫™

∂ÈÎfiÓ· 2. ™˘ÓÂÚÁÈÎ‹ ‰Ú¿ÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ Î·È ‚2-·ÁˆÓÈÛÙÒÓ ÛÂ Î˘ÙÙ·ÚÈÎfi Â›Â‰Ô. ∏ ‰È¤ÁÂÚÛË ÙÔ˘ ‚2-˘Ô‰Ô¯¤· ·fi ÙÔÓ ‚2-·ÁˆÓÈÛÙ‹ ÚÔÎ·ÏÂ› ·‡ÍËÛË ÙË˜ Û˘ÁÎ¤ÓÙÚˆÛË˜ ÙÔ˘ ÂÓ‰ÔÎ˘ÙÙ¿ÚÈÔ˘ cAMP, Ô˘ ÌÂ ÙË ÛÂÈÚ¿ ÙÔ˘ Â›ÙÂ ¿ÌÂÛ·, ÂÓÂÚÁÔÔÈÒÓÙ·˜ ÙËÓ PKA, Â›ÙÂ ¤ÌÌÂÛ·, Ì¤Ûˆ ÂÓÂÚÁÔÔ›ËÛË˜ ÙË˜ MAPK, ÚÔ¿ÁÂÈ ÙË ÌÂÙÂÁÎ·Ù¿ÛÙ·ÛË ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ ÛÙÈ˜ GRE ÂÚÈÔ¯¤˜ ÙÔ˘ ÁÔÓÈ‰ÈÒÌ·ÙÔ˜, ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÂÈ‰ÈÎÒÓ ÁÔÓÈ‰›ˆÓ Î·È ÙËÓ ·Ú·ÁˆÁ‹ ÚˆÙÂ˚ÓÒÓ ÌÂ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË. ∫™: ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰¤˜, GRE: glucocorticosteroid response element, PKA: protein kinase A, MAPK: mitogen-activated protein kinases [·fi Barnes PJ (10), ÙÚÔÔÔÈËÌ¤ÓÔ]. ¶·È‰È·ÙÚÈÎ‹ 2006;69:417-424

420

ª. B. ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜, ∫. ¡. ¶Ú›ÊÙË˜

ªÂÙ·‚ÔÏ‹ FEV1(%)

20 15 10 5 0 -5

ªÂÎÏÔÌÂı·˙ﬁÓË ™·ÏÌÂÙÂÚﬁÏË

-10 -15

6 12 18 24 30 36 42 48 54 ∂·Ó¤ÏÂÁ¯Ô˜ ¢È¿ÚÎÂÈ· ıÂÚ·Â›·˜ (Â‚‰ÔÌ¿‰Â˜)

∂ÈÎfiÓ· 3. ªÂÙ·‚ÔÏ‹ ÙÔ˘ FEV1 ·ÛıÌ·ÙÈÎÒÓ ·È‰ÈÒÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÌÔÓÔıÂÚ·Â›·˜ ÌÂ Û·ÏÌÂÙÂÚfiÏË ¤Ó·ÓÙÈ ÌÂÎÏÔÌÂı·˙fiÓË˜ (200 Ìg x 2) Â› ¤Ó· ¤ÙÔ˜. ∏ ÌÔÓÔıÂÚ·Â›· ÌÂ Û·ÏÌÂÙÂÚfiÏË ÚÔÎ·ÏÂ› ÂÈ‰Â›ÓˆÛË ÙË˜ ‚ÚÔÁ¯ÔÛÙ¤ÓˆÛË˜ (·fi ÙË ‰ÈÏ‹ Ù˘ÊÏ‹ Ù˘¯·ÈÔÔÈËÌ¤ÓË ÌÂÏ¤ÙË ÛÂ 67 ·È‰È¿ ËÏÈÎ›·˜ 6-16 ÂÙÒÓ ÙˆÓ Verberne AA Î·È Û˘Ó (14), ÙÚÔÔÔÈËÌ¤ÓÔ). ¶·È‰È·ÙÚÈÎ‹ 2006;69:417-424

ÙË˜ ÌÔÓÔıÂÚ·Â›·˜ ÌÂ ‰ÈÏ¿ÛÈ· ‰fiÛË ∂ÈÛ∫™ ÛÙÔÓ Ì·ÎÚÔ¯ÚfiÓÈÔ ¤ÏÂÁ¯Ô ÙË˜ ÓfiÛÔ˘ (3,4). º·›ÓÂÙ·È fiÙÈ Ë ‚ÂÏÙ›ˆÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Ô˘ ÚÔÎ‡ÙÂÈ ·fi ÙÔÓ Û˘Ó‰˘·ÛÌfi ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÌÂ ¯·ÌËÏ‹ ‰fiÛË ∂ÈÛ∫™ ‰ÂÓ “Û˘ÁÎ·Ï‡ÙÂÈ” ÙËÓ ‡·ÚÍË Â›ÌÔÓË˜ ‹ ÂÈ‰ÂÈÓÔ‡ÌÂÓË˜ ·ÛıÌ·ÙÈÎ‹˜ ÊÏÂÁÌÔÓ‹˜ (19). ∂ÔÌ¤Óˆ˜, Ô ¤ÏÂÁ¯Ô˜ ÙË˜ ¯ÚfiÓÈ·˜ ÓfiÛÔ˘ ÌÂ Û˘Ó‰˘·ÛÌ¤ÓË ıÂÚ·Â›· ‰ÂÓ ·ÔÚÔÛ·Ó·ÙÔÏ›˙ÂÈ ÙÔÓ ÎÏÈÓÈÎfi ÁÈ·ÙÚfi, ÒÛÙÂ Ó· ˘ÂÚÙÈÌ‹ÛÂÈ ÙÔÓ ¤ÏÂÁ¯Ô ÙË˜ ÓfiÛÔ˘ Î·È Ó· ˘ÔÙÈÌ‹ÛÂÈ ÙÈ˜ Ú·ÁÌ·ÙÈÎ¤˜ ·Ó¿ÁÎÂ˜ ÙÔ˘ ·ÛıÌ·ÙÈÎÔ‡ ·ÛıÂÓÔ‡˜ ÛÂ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ·ÁˆÁ‹ (20). √ ·ÚÈıÌfi˜ ÙˆÓ Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ‰ÈÏÒÓÙ˘ÊÏÒÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ Ô˘ ‰ÈÂÚÂ˘ÓÔ‡Ó ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙË˜ Û˘Ó‰˘·˙fiÌÂÓË˜ ıÂÚ·Â›·˜ ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÛÙ· ·È‰È¿ Â›Ó·È Ì¿ÏÏÔÓ ÂÚÈÔÚÈÛÌ¤ÓÔ˜ Î·È ·ÊÔÚ¿ ÛÂ ËÏÈÎ›Â˜ ¿Óˆ ÙˆÓ 4-6 ÂÙÒÓ (21-28). ™¯Â‰fiÓ fiÏÂ˜ ‰Â›¯ÓÔ˘Ó ‰È·ÊfiÚÔ˘ ‚·ıÌÔ‡ ˘ÂÚÔ¯‹ ÙË˜ Û˘Ó‰˘·˙fiÌÂÓË˜ ıÂÚ·Â›·˜ ˆ˜ ÚÔ˜ ÙÔ˘˜ ‰Â›ÎÙÂ˜ ÂÏ¤Á¯Ô˘ ÙË˜ ¯ÚfiÓÈ·˜ ÓfiÛÔ˘ [‚·ıÌÔÏÔÁ›· Û˘ÌÙˆÌ¿ÙˆÓ, ËÌ¤ÚÂ˜ ÂÏÂ‡ıÂÚÂ˜ Û˘ÌÙˆÌ¿ÙˆÓ, ¯Ú‹ÛË ·Ó·ÎÔ˘ÊÈÛÙÈÎ‹˜ ıÂÚ·Â›·˜, FEV1 (‚›·È· ÂÎÓÂfiÌÂÓÔ˜ fiÁÎÔ˜ ÛÙÔ ÚÒÙÔ ‰Â˘ÙÂÚfiÏÂÙÔ), ÚˆÈÓ‹ Î·È ‚Ú·‰ÈÓ‹ PEF (Ì¤ÁÈÛÙË ÂÎÓÂ˘ÛÙÈÎ‹ ÚÔ‹), ÌÂÙ·‚ÏËÙfiÙËÙ· PEF, ˘ÂÚ··ÓÙËÙÈÎfiÙËÙ·] ÛÂ Û¯¤ÛË ÌÂ ÙË ÌÔÓÔıÂÚ·Â›· ÌÂ ∂ÈÛ∫™ (∂ÈÎfiÓÂ˜ 4 Î·È 5) (21-27). øÛÙfiÛÔ, Ë ÌÂÏ¤ÙË ÙˆÓ Verberne Î·È Û˘Ó (28) ‰ÂÓ ·Ó·‰ÂÈÎÓ‡ÂÈ ˘ÂÚÔ¯‹ ÙË˜ Û˘Ó‰˘·˙fiÌÂÓË˜ ıÂÚ·Â›·˜ ¤Ó·ÓÙÈ ÙË˜ ÌÔÓÔıÂÚ·Â›·˜ ÌÂ ‰‡Ô

¢È¿ÌÂÛË ÙÈÌ‹ ËÌÂÚÒÓ ¯ˆÚ›˜ Û˘ÌÙÒÌ·Ù· (%)

∫ÏÈÓÈÎ¿ ‰Â‰ÔÌ¤Ó· ÁÈ· ÙÔÓ Û˘Ó‰˘·ÛÌfi ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙÒÓ ÛÙ· ·È‰È¿ ∏ ÌÔÓÔıÂÚ·Â›· ÙÔ˘ ¿ÛıÌ·ÙÔ˜ ÌÂ ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ‰ÂÓ ÂÓ‰Â›ÎÓ˘Ù·È, ÏfiÁˆ ÙÔ˘ Êfi‚Ô˘ ·Ó·˙ˆ‡ÚˆÛË˜ ÙË˜ ÊÏÂÁÌÔÓ‹˜ ÙˆÓ ·ÂÚ·ÁˆÁÒÓ, ·Ú¿ ÙË Û‡Á¯ÚÔÓË ÎÏÈÓÈÎ‹ ‚ÂÏÙ›ˆÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ (12,13). ¶Ú¿ÁÌ·ÙÈ, ÔÈ Verberne Î·È Û˘Ó ¤‰ÂÈÍ·Ó fiÙÈ Ë ÌÔÓÔıÂÚ·Â›· ·ÛıÌ·ÙÈÎÒÓ ·È‰ÈÒÓ ÌÂ Û·ÏÌÂÙÂÚfiÏË ÁÈ· ¤Ó· ¤ÙÔ˜ Ô‰‹ÁËÛÂ ÌÂÓ ÛÂ ‚ÂÏÙ›ˆÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ, fiÌˆ˜ Ë ÎÏÈÓÈÎ‹ ‚ÂÏÙ›ˆÛË ˘ÔÏÂÈfiÙ·Ó ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÙË ¯ÔÚ‹ÁËÛË ÌÔÓÔıÂÚ·Â›·˜ ÌÂ ÌÂÎÏÔÌÂı·˙fiÓË (200 Ìg x 2). ∞ÎfiÌË ÈÔ ·ÓËÛ˘¯ËÙÈÎfi ‹Ù·Ó ÙÔ Â‡ÚËÌ· ÙË˜ ÌÂÏ¤ÙË˜ fiÙÈ Ë ‚ÚÔÁ¯ÔÛÙ¤ÓˆÛË Î·È Ë ‚ÚÔÁ¯ÈÎ‹ ˘ÂÚ··ÓÙËÙÈÎfiÙËÙ· ÂÈ‰ÂÈÓÒıËÎ·Ó ÛÂ Û¯¤ÛË ÌÂ ÙË ‚·ÛÈÎ‹ ÙÈÌ‹ ÛÙËÓ ÔÌ¿‰· ÙË˜ Û·ÏÌÂÙÂÚfiÏË˜, ÂÓÒ ·ÓÙ›ıÂÙ· ·ÚÔ˘Û›·Û·Ó ‚ÂÏÙ›ˆÛË ÛÙËÓ ÔÌ¿‰· ÙË˜ ÌÂÎÏÔÌÂı·˙fiÓË˜ (∂ÈÎfiÓ· 3) (14). ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿, Î·ıÒ˜ Î·È ¿ÏÏ· (15), ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ¿Ô„Ë fiÙÈ Ë ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛË ÙˆÓ ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ Ô‰ËÁÂ› ÛÙËÓ ÂÌÊ¿ÓÈÛË ÙÔ˘ Ê·ÈÓÔÌ¤ÓÔ˘ ÙË˜ ·ÓÔ¯‹˜ ÛÙËÓ ÂÎ‰‹ÏˆÛË ÙË˜ ‚ÚÔÁ¯ÔÚÔÛÙ·ÙÂ˘ÙÈÎ‹˜ ‰Ú¿ÛË˜ ÙÔ˘˜. ∂ÓÙÔ‡ÙÔÈ˜, ·ÔÙÂÏ¤ÛÌ·Ù· ¿ÏÏˆÓ ÌÂÏÂÙÒÓ Û˘ÓËÁÔÚÔ‡Ó ÁÈ· ÙÔ ·ÓÙ›ıÂÙÔ (16). ªÈ· ÛÂÈÚ¿ ·fi Î·Ï¿ Û¯Â‰È·ÛÌ¤ÓÂ˜ ÎÏÈÓÈÎ¤˜ ÌÂÏ¤ÙÂ˜ ÛÂ ÂÓ‹ÏÈÎÂ˜ ·ÛıÌ·ÙÈÎÔ‡˜ ·ÛıÂÓÂ›˜ ¤¯ÂÈ ‰Â›ÍÂÈ fiÙÈ Ë ÚÔÛı‹ÎË ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÛÂ ¯·ÌËÏ‹ ‹ Ì¤ÙÚÈ· ‰fiÛË ∂ÈÛ∫™ ‚ÂÏÙÈÒÓÂÈ ÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ·ÛıÌ·ÙÈÎÒÓ Û˘ÌÙˆÌ¿ÙˆÓ Î·È ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÂÏ·ÙÙÒÓÂÈ ÙÔ˘˜ ·ÚÔÍ˘ÛÌÔ‡˜ ÙË˜ ÓfiÛÔ˘ (3-5,17,18), ÂÓÒ Ô Û˘Ó‰˘·ÛÌfi˜ ÙˆÓ ‰‡Ô Î·ÙËÁÔÚÈÒÓ Ê·ÚÌ¿ÎˆÓ Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚÔ˜

(p=0,043) (p=0,008)

60 50

(p<0,001)

40 30

™·ÏÌÂÙÂÚﬁÏË (50 Ìg x 2) ∂ÈÎÔÓÈÎﬁ Ê¿ÚÌ·ÎÔ

20 10 0 ∆ÈÌ‹ 1-4 5-8 9-12 ·Ó·ÊÔÚ¿˜ Â‚‰ÔÌ¿‰Â˜ Â‚‰ÔÌ¿‰Â˜ Â‚‰ÔÌ¿‰Â˜

∂ÈÎfiÓ· 4. ¶ÔÛÔÛÙfi ËÌÂÚÒÓ ¯ˆÚ›˜ Û˘ÌÙÒÌ·Ù· (‰È¿ÌÂÛË ÙÈÌ‹) ÛÂ ·È‰È¿ ÌÂ Ì¤ÙÚÈÔ ‹ ÛÔ‚·Úfi ¿ÛıÌ· ˘fi Ì·ÎÚÔ¯ÚfiÓÈ· ·ÁˆÁ‹ ÌÂ ÙÔ˘Ï¿¯ÈÛÙÔÓ 400 Ìg ÌÂÎÏÔÌÂı·˙fiÓË˜ ËÌÂÚËÛ›ˆ˜ ‹ ÈÛÔ‰‡Ó·ÌË˜ ‰fiÛË˜ ¿ÏÏÔ˘ ∂ÈÛ∫™, Ô˘ ¤Ï·‚·Ó Û·ÏÌÂÙÂÚfiÏË ¤Ó·ÓÙÈ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ Â› 12 Â‚‰ÔÌ¿‰Â˜ (·fi ÙË ‰ÈÏ‹-Ù˘ÊÏ‹ Ù˘¯·ÈÔÔÈËÌ¤ÓË ÌÂÏ¤ÙË ÛÂ 210 ·È‰È¿ ËÏÈÎ›·˜ 4-16 ÂÙÒÓ ÙˆÓ Russell G Î·È Û˘Ó (22), ÙÚÔÔÔÈËÌ¤ÓÔ).

∂ÈÛÓÂﬁÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ Î·È ‚2-·ÁˆÓÈÛÙ¤˜ ÛÙÔ ·È‰ÈÎﬁ ¿ÛıÌ·

µÔ˘‰ÂÛÔÓ›‰Ë 160 Ìg x 2 ∫∞π ÊÔÚÌÔÙÂÚﬁÏË 9 Ìg x 2 µÔ˘‰ÂÛÔÓ›‰Ë 200 Ìg x 2

FEV1(%)

120 115

p<0,05

110 105 100

4 8 £ÂÚ·Â›· (Â‚‰ÔÌ¿‰Â˜)

∂ÈÎfiÓ· 5. √ FEV1 ‹Ù·Ó ˘„ËÏfiÙÂÚÔ˜ ÛÙËÓ ÔÌ¿‰· ÙˆÓ ·È‰ÈÒÓ Ô˘ ¤Ï·‚Â Û˘Ó‰˘·˙fiÌÂÓË ıÂÚ·Â›· ÌÂ ‚Ô˘‰ÂÛÔÓ›‰Ë (160 Ìg x 2) Î·È ÊÔÚÌÔÙÂÚfiÏË (9 Ìg x 2) ¤Ó·ÓÙÈ ÙË˜ ÔÌ¿‰·˜ Ô˘ ¤Ï·‚Â ÌÔÓÔıÂÚ·Â›· ÌÂ ›‰È· ‰fiÛË ‚Ô˘‰ÂÛÔÓ›‰Ë˜ (·fi ÙË ‰ÈÏ‹-Ù˘ÊÏ‹ Ù˘¯·ÈÔÔÈËÌ¤ÓË ÌÂÏ¤ÙË 12 Â‚‰ÔÌ¿‰ˆÓ ÛÂ 286 ·ÛıÌ·ÙÈÎ¿ ·È‰È¿ ËÏÈÎ›·˜ 4-17 ÂÙÒÓ ÙˆÓ Tal A Î·È Û˘Ó (26), ÙÚÔÔÔÈËÌ¤ÓÔ).

‰È·ÊÔÚÂÙÈÎ¤˜ ‰fiÛÂÈ˜ ∂ÈÛ∫™. ¶ÚfiÎÂÈÙ·È ÁÈ· ‰ÈÏ‹-Ù˘ÊÏ‹ ÌÂÏ¤ÙË, ÂÏÂÁ¯fiÌÂÓË ÌÂ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ, Ô˘ ÂÚÈ¤Ï·‚Â 177 ·È‰È¿ ËÏÈÎ›·˜ 616 ÂÙÒÓ, Ù· ÔÔ›· ¯ˆÚ›ÛÙËÎ·Ó ÛÂ ÙÚÂÈ˜ ÔÌ¿‰Â˜ (ÔÌ¿‰· ∞: ÌÂÎÏÔÌÂı·˙fiÓË 200 Ìg x 2 Î·È Û·ÏÌÂÙÂÚfiÏË 50 Ìg x 2, ÔÌ¿‰· µ: ÌÂÎÏÔÌÂı·˙fiÓË 400 Ìg x 2, ÔÌ¿‰· °: ÌÂÎÏÔÌÂı·˙fiÓË 200 Ìg x 2) Î·È ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó ÁÈ· 12 Ì‹ÓÂ˜. ¢ÂÓ ‚Ú¤ıËÎ·Ó ‰È·ÊÔÚ¤˜ ÛÙÔÓ FEV1, ÙËÓ PD20 (‰fiÛË ÚfiÎÏËÛË˜ ÙÒÛË˜ ÙÔ˘ FEV1 Î·Ù¿ 20%) ÌÂÙ¿ ÚfiÎÏËÛË ÌÂ ÌÂÙ·¯ÔÏ›ÓË, ÛÙË ‚·ıÌÔÏÔÁ›· ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Î·È ÛÙË Û˘¯ÓfiÙËÙ· ÙˆÓ ·ÚÔÍ˘ÛÌÒÓ ÌÂÙ·Í‡ ÙˆÓ ÙÚÈÒÓ ÔÌ¿‰ˆÓ. À‹ÚÍ·Ó ÌfiÓÔ Î¿ÔÈÂ˜ ÌÈÎÚ¤˜ ‰È·ÊÔÚ¤˜ ÛÙËÓ ÚˆÈÓ‹ Î·È ‚Ú·‰ÈÓ‹ PEF ˘¤Ú ÙË˜ ÔÌ¿‰·˜ Ô˘ Ï¿Ì‚·ÓÂ Û·ÏÌÂÙÂÚfiÏË Î·Ù¿ ÙÔ˘˜ ÚÒÙÔ˘˜ Ì‹ÓÂ˜ ıÂÚ·Â›·˜. ™ËÌÂÈÒÓÂÙ·È fiÙÈ ÛÙËÓ ÔÌ¿‰· Ô˘ ¤Ï·‚Â ˘„ËÏ‹ ‰fiÛË ÌÂÎÏÔÌÂı·˙fiÓË˜ ·Ú·ÙËÚ‹ıËÎ·Ó ¯·ÌËÏfiÙÂÚÔÈ Ú˘ıÌÔ› ·‡ÍËÛË˜. ∞fi ÙÔ 1998 Ô Û˘Ó‰˘·ÛÌfi˜ Û·ÏÌÂÙÂÚfiÏË˜/ÊÏÔ˘ÙÈÎ·˙fiÓË˜ Î·È ·fi ÙÔ 2000 Ô Û˘Ó‰˘·ÛÌfi˜ ‚Ô˘‰ÂÛÔÓ›‰Ë˜/ÊÔÚÌÔÙÂÚfiÏË˜ ÌÔÚÔ‡Ó Ó· Û˘Á¯ÔÚËÁËıÔ‡Ó, Î·ı¤Ó·˜ ÌÂ ÂÓÈ·›· Û˘ÛÎÂ˘‹. Œ¯ÂÈ ‰ÂÈ¯ıÂ›, Ì¿ÏÈÛÙ·, fiÙÈ Ë Û˘Á¯ÔÚ‹ÁËÛË ·˘Ù‹ ÛÙ· ·È‰È¿, fiˆ˜ Î·È ÛÙÔ˘˜ ÂÓ‹ÏÈÎÂ˜, Â›Ó·È ÙÔ˘Ï¿¯ÈÛÙÔÓ ÂÍ›ÛÔ˘ ·ÔÙÂÏÂÛÌ·ÙÈÎ‹ Î·È ·ÛÊ·Ï‹˜ ÌÂ ÙË ‰È·‰Ô¯ÈÎ‹ ¯ÔÚ‹ÁËÛË ÙˆÓ Ê·ÚÌ¿ÎˆÓ ÙÔ˘ Î¿ıÂ Û˘Ó‰˘·ÛÌÔ‡ ÌÂ ÍÂ¯ˆÚÈÛÙ¤˜ Û˘ÛÎÂ˘¤˜ (29-31). √ÚÈÛÌ¤ÓÔÈ Ì¿ÏÈÛÙ· ˘ÔÛÙËÚ›˙Ô˘Ó, ÛÂ ıÂˆÚËÙÈÎ‹ Î˘Ú›ˆ˜ ‚¿ÛË, fiÙÈ ˘¿Ú¯ÂÈ Û˘Ó¤ÚÁÂÈ· ÙˆÓ ‰‡Ô Î·ÙËÁÔÚÈÒÓ Ê·ÚÌ¿ÎˆÓ fiÙ·Ó ·˘Ù¿ Û˘Á¯ÔÚËÁÔ‡ÓÙ·È ÛÂ Ì›· ÂÈÛÓÔ‹ (32). ™ËÌÂÈÒÓÂÙ·È fiÙÈ ·fi ÙÈ˜ ÚÔ·Ó·ÊÂÚıÂ›ÛÂ˜ ÌÂÏ¤ÙÂ˜ ÙË˜ Û˘Ó‰˘·˙fiÌÂÓË˜ ıÂÚ·Â›·˜ ÛÂ ·È‰È·ÙÚÈÎÔ‡˜ ·ÛıÂÓÂ›˜, ÌfiÓÔ ÛÂ ÂÎÂ›ÓË ÙˆÓ

421

Tal Î·È Û˘Ó (26) ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ ÂÓÈ·›· Û˘ÛÎÂ˘‹. ∆¤ÏÔ˜, ·Ó Î·È Ù· ‰Â‰ÔÌ¤Ó· ÁÈ· ÙËÓ Â›‰Ú·ÛË ÙË˜ Ù·˘Ùfi¯ÚÔÓË˜ ¯ÔÚ‹ÁËÛË˜ ∂ÈÛ∫™ Î·È ‚2·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÌÂ ÂÓÈ·›· Û˘ÛÎÂ˘‹ ÛÙË “Û˘ÌÌfiÚÊˆÛË” ÙˆÓ ·ÛıÌ·ÙÈÎÒÓ ·ÛıÂÓÒÓ Â›Ó·È ÂÏ¿¯ÈÛÙ·, Ê·›ÓÂÙ·È fiÙÈ ·˘Ù‹ ‚ÂÏÙÈÒÓÂÈ ÙË Û˘ÌÌfiÚÊˆÛË (33).

∏ Â›ÙÂ˘ÍË È‰·ÓÈÎÔ‡ ÂÏ¤Á¯Ô˘ ÙÔ˘ ¿ÛıÌ·ÙÔ˜ √ Ï‹ÚË˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ¿ÛıÌ·ÙÔ˜, fiˆ˜ ·˘Ùfi˜ ÔÚ›˙ÂÙ·È ÛÙÈ˜ ÙÚ¤¯Ô˘ÛÂ˜ ÔÌÔÊˆÓ›Â˜ (2,6,7) ‰ÂÓ Â›Ó·È ÂÊÈÎÙfi˜ ÛÂ ·ÚÎÂÙÔ‡˜ ·ÛıÂÓÂ›˜. ™Â ÚfiÛÊ·ÙË ÌÂÁ¿ÏË 12ÌËÓË ÌÂÏ¤ÙË ÙˆÓ Bateman Î·È Û˘Ó (34) ÛÂ ÂÓ‹ÏÈÎÂ˜ ·ÛıÌ·ÙÈÎÔ‡˜ (ÂÚÈÛÛfiÙÂÚÔÈ ·fi 3000 ·ÛıÂÓÂ›˜) ÂÈ¯ÂÈÚ‹ıËÎÂ Ó· ÂÈÙÂ˘¯ıÂ› Ô ‚¤ÏÙÈÛÙÔ˜ - Î·È ÂÊfiÛÔÓ ‹Ù·Ó ‰˘Ó·Ùfi - Ô Ï‹ÚË˜ ¤ÏÂÁ¯Ô˜ ÙË˜ ÓfiÛÔ˘ ÌÂ ÚÔÔ‰Â˘ÙÈÎ‹ ·‡ÍËÛË ÙË˜ ‰fiÛË˜ ÙÔ˘ ÂÈÛÓÂfiÌÂÓÔ˘ Ê·ÚÌ¿ÎÔ˘ Ú‡ıÌÈÛË˜. ∏ ÌÂÏ¤ÙË ·˘Ù‹ ¤‰ÂÈÍÂ fiÙÈ Ë Û˘Á¯ÔÚ‹ÁËÛË Û·ÏÌÂÙÂÚfiÏË˜/ÊÏÔ˘ÙÈÎ·˙fiÓË˜ ÌÂ ÙËÓ ›‰È· Û˘ÛÎÂ˘‹ ÂÈÙ˘Á¯¿ÓÂÈ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚÔ ¤ÏÂÁ¯Ô ÙË˜ ÓfiÛÔ˘ ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÙË ¯ÔÚ‹ÁËÛË ÌfiÓË˜ ÙË˜ ÊÏÔ˘ÙÈÎ·˙fiÓË˜, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ Ì¿ÏÈÛÙ· ÌÈÎÚfiÙÂÚË ËÌÂÚ‹ÛÈ· ‰fiÛË ∂ÈÛ∫™. ¶·Ú’ fiÏ· ·˘Ù¿, ÔÚÈÛÌ¤ÓÔÈ ·ÛıÂÓÂ›˜ ¯ÚÂÈ¿ÛÙËÎÂ Ó· Ï¿‚Ô˘Ó ˘„ËÏ¤˜ ‰fiÛÂÈ˜ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰Ô‡˜ ÚÔÎÂÈÌ¤ÓÔ˘ Ó· ÂÏÂÁ¯ıÂ› Ë ÓfiÛÔ˜ ÙÔ˘˜ (34). ¶·ÚfiÌÔÈ· ÚÔÛ¤ÁÁÈÛË ‰ÂÓ ¤¯ÂÈ ÌÂÏÂÙËıÂ› ÚÔ˜ ÙÔ ·ÚfiÓ ÛÙ· ·È‰È¿. ™Â ¿ÏÏË ÌÂÁ¿ÏË 12ÌËÓË ÌÂÏ¤ÙË, ÙˆÓ O’Byrne Î·È Û˘Ó (ÂÚ›Ô˘ 2700 ·ÛıÂÓÂ›˜) (35), ¤ÁÈÓÂ ÚÔÛ¿ıÂÈ· Ó· ·ÍÈÔÔÈËıÂ› Ë ‰˘Ó·ÙfiÙËÙ· ÙË˜ ÊÔÚÌÔÙÂÚfiÏË˜ Ó· ¯ÚËÛÈÌÔÔÈÂ›Ù·È ˆ˜ ·Ó·ÎÔ˘ÊÈÛÙÈÎfi ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎfi Ê¿ÚÌ·ÎÔ ÏfiÁˆ ÙË˜ Ù·¯Â›·˜ ¤Ó·ÚÍË˜ ‰Ú¿ÛË˜ ÙË˜ (36,37). ™ÙË ÌÂÏ¤ÙË ·˘Ù‹ Û˘ÁÎÚ›ıËÎÂ Ë Û˘Á¯ÔÚ‹ÁËÛË ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ‚Ô˘‰ÂÛÔÓ›‰Ë˜/ÊÔÚÌÔÙÂÚfiÏË˜ (80/4,5 Ìg x 2) ÛÙËÓ ›‰È· Û˘ÛÎÂ˘‹ ˆ˜ ıÂÚ·Â›· Û˘ÓÙ‹ÚËÛË˜, ·ÏÏ¿ Î·È ˆ˜ ·Ó·ÎÔ˘ÊÈÛÙÈÎ‹ ıÂÚ·Â›· (Ë ›‰È· ‰fiÛË ˆ˜ Î·Ù’ Â›ÎÏËÛÈÓ ÂÈÛÓÔ¤˜) ÌÂ ‰‡Ô Û¯‹Ì·Ù· “ÎÏ·ÛÈÎ‹˜” ÚÔÊ˘Ï·ÎÙÈÎ‹˜ ¯ÔÚ‹ÁËÛË˜ (80/4,5 Ìg x 2 Î·È 320/4,5 Ìg x 2) Î·È ¯Ú‹ÛË ‚2-·ÁˆÓÈÛÙ‹ ‚Ú·¯Â›·˜ ‰Ú¿ÛË˜ ÂÊfiÛÔÓ ¯ÚÂÈ·˙fiÙ·Ó ÁÈ· ·Ó·ÎÔ‡ÊÈÛË. √ ¤ÏÂÁ¯Ô˜ ÙË˜ ÓfiÛÔ˘ ˆ˜ ÚÔ˜ ÙÔ˘˜ ·ÛıÌ·ÙÈÎÔ‡˜ ·ÚÔÍ˘ÛÌÔ‡˜, Ù· Û˘ÌÙÒÌ·Ù· Î·È ÙËÓ ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· ‹Ù·Ó ÏËÚ¤ÛÙÂÚÔ˜ ÛÙËÓ ÔÌ¿‰· Ô˘ ¤Ï·‚Â ÙÔÓ Û˘Ó‰˘·ÛÌfi ˆ˜ ÚÔÊ˘Ï·ÎÙÈÎ‹, ·ÏÏ¿ Î·È ˆ˜ ·Ó·ÎÔ˘ÊÈÛÙÈÎ‹ ıÂÚ·Â›· ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÙÈ˜ ¿ÏÏÂ˜ ‰‡Ô ¶·È‰È·ÙÚÈÎ‹ 2006;69:417-424

422

ª. B. ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜, ∫. ¡. ¶Ú›ÊÙË˜

ÔÌ¿‰Â˜. ¢ÂÓ ·Ú·ÙËÚ‹ıËÎÂ Î·Ù¿¯ÚËÛË Ê·ÚÌ¿ÎÔ˘ (35). ∆· ıÂÙÈÎ¿ ·ÔÙÂÏ¤ÛÌ·Ù· ÙË˜ “ÌË Û˘Ì‚·ÙÈÎ‹˜” Û˘Á¯ÔÚ‹ÁËÛË˜ ‚Ô˘‰ÂÛÔÓ›‰Ë˜/ÊÔÚÌÔÙÂÚfiÏË˜ ÌÂ ÎÔÈÓ‹ Û˘ÛÎÂ˘‹, ÙfiÛÔ ÁÈ· ÙË Ì·ÎÚÔ¯ÚfiÓÈ· ÚÔÊ‡Ï·ÍË ÙÔ˘ ¿ÛıÌ·ÙÔ˜ fiÛÔ Î·È ÁÈ· ÙËÓ Î·Ù’ Â›ÎÏËÛÈÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ÙË˜ ÓfiÛÔ˘, Á›ÓÔÓÙ·È Î·Ù·ÓÔËÙ¿ Â¿Ó Ï¿‚ÂÈ Î·ÓÂ›˜ ˘’ fi„ÈÓ Ù· ·ÎfiÏÔ˘ı·: ·) √È ·ÚÔÍ˘ÛÌÔ› ÙË˜ ÓfiÛÔ˘ ÂÎ‰ËÏÒÓÔÓÙ·È Û˘Ó‹ıˆ˜ ÂÓÙfi˜ ‰È·ÛÙ‹Ì·ÙÔ˜ ÌÂÚÈÎÒÓ ÌfiÓÔ ËÌÂÚÒÓ (38), ‰›ÓÔÓÙ·˜ ¤ÙÛÈ ÛÙÔÓ ·ÛıÂÓ‹ ÙËÓ Â˘Î·ÈÚ›· Ó· ÍÂÎÈÓ‹ÛÂÈ ¤ÁÎ·ÈÚ· ÙËÓ “ÂÓÈÛ¯˘Ì¤ÓË” ·Ó·ÎÔ˘ÊÈÛÙÈÎ‹ ıÂÚ·Â›· ÌÂ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰¤˜. ‚) ∆fiÛÔ Ë ‚Ô˘‰ÂÛÔÓ›‰Ë (39) fiÛÔ Î·È Ë ÊÏÔ˘ÙÈÎ·˙fiÓË (40) ÂÎ‰ËÏÒÓÔ˘Ó ÙËÓ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË ÙÔ˘˜ ÔÏ‡ ÓˆÚ›ÙÂÚ· ·fi fi,ÙÈ ıÂˆÚÂ›ÙÔ ·Ï·ÈfiÙÂÚ·. ∞Ó Î·È Ë ÌÂÏ¤ÙË ÙˆÓ O’Byrne Î·È Û˘Ó (35) ÂÚÈÂÏ¿Ì‚·ÓÂ Î·È 341 ·È‰È¿ ËÏÈÎ›·˜ 4-11 ÂÙÒÓ (12% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ·ÛıÂÓÒÓ), Ù· ·ÔÙÂÏ¤ÛÌ·Ù· ÁÈ’ ·˘Ù‹ ÙËÓ ËÏÈÎÈ·Î‹ ÔÌ¿‰· ‰ÂÓ ¤¯Ô˘Ó Á›ÓÂÈ ÚÔ˜ ÙÔ ·ÚfiÓ ÁÓˆÛÙ¿. ∆· ÔÏ‡ ÂÓ‰È·Ê¤ÚÔÓÙ· Â˘Ú‹Ì·Ù· ÙˆÓ ‰‡Ô ·Ú·¿Óˆ ÌÂÏÂÙÒÓ Ú¤ÂÈ Ó· ÂÈ‚Â‚·ÈˆıÔ‡Ó ÛÂ ÌÂÁ·Ï‡ÙÂÚÔ˘˜ ÏËı˘ÛÌÔ‡˜, ÂÓÒ ‰ÂÓ ¤¯ÂÈ ÚÔ˜ ÙÔ ·ÚfiÓ ·Ô‰ÂÈ¯ıÂ› Ë ÈÛ¯‡˜ ÙÔ˘˜ Î·È ÛÙ· ·È‰È¿.

™˘ÌÂÚ¿ÛÌ·Ù· ÃˆÚ›˜ ·ÌÊÈ‚ÔÏ›·, Ù· Ì¤¯ÚÈ Û‹ÌÂÚ· ÂÈÛÙËÌÔÓÈÎ¿ ‰Â‰ÔÌ¤Ó· ·Ó·‰ÂÈÎÓ‡Ô˘Ó ÙÔÓ ·ıÚÔÈÛÙÈÎfi ÚfiÏÔ ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙÒÓ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÛÙÔÓ Ì·ÎÚÔ¯ÚfiÓÈÔ ¤ÏÂÁ¯Ô ÙÔ˘ ¿ÛıÌ·ÙÔ˜, ÂÓÒ ÔÈ ÚfiÔ‰ÔÈ ÛÙË ‚·ÛÈÎ‹ ¤ÚÂ˘Ó· ÔÏÔ¤Ó· Î·È ÂÚÈÛÛfiÙÂÚÔ ÊˆÙ›˙Ô˘Ó ÙË Û˘ÓÂÚÁÈÎ‹ ‰Ú¿ÛË ÙˆÓ ‰‡Ô ·˘ÙÒÓ Î·ÙËÁÔÚÈÒÓ ·ÓÙÈ·ÛıÌ·ÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÛÂ Î˘ÙÙ·ÚÈÎfi Â›Â‰Ô (41). øÛÙfiÛÔ, Ë Ì·ÎÚÔ¯ÚfiÓÈ· ÌÔÓÔıÂÚ·Â›· ÌÂ ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ÌÔÚÂ› Ó· Ô‰ËÁ‹ÛÂÈ ÛÂ ÂÈ‰Â›ÓˆÛË ÙÔ˘ ¿ÛıÌ·ÙÔ˜ Î·È, Û‡ÌÊˆÓ· ÌÂ ÙÈ˜ ÚfiÛÊ·ÙÂ˜ ÔÌÔÊˆÓ›Â˜, ‰ÂÓ ¤¯ÂÈ ı¤ÛË ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙË˜ ÓfiÛÔ˘ (14,42). ™ÙËÓ ÎÏÈÓÈÎ‹ Ú¿ÍË, Ô Û˘Ó‰˘·ÛÌfi˜ ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ ¯ÔÚËÁÂ›Ù·È ÛÙÔ Ì¤ÙÚÈÔ Î·È ÛÔ‚·Úfi (Â›ÌÔÓÔ) ¿ÛıÌ· Î·È ·ÔÙÂÏÂ› ÙË ıÂÚ·Â›· ÂÎÏÔÁ‹˜ ÛÙÔ ‹ÈÔ Â›ÌÔÓÔ ·È‰ÈÎfi ¿ÛıÌ· Ô˘ ‰ÂÓ ÂÏ¤Á¯ÂÙ·È ÌÂ ¯·ÌËÏ¤˜ ‰fiÛÂÈ˜ ∂ÈÛ∫™, ÚˆÙ›ÛÙˆ˜ ·È‰ÈÒÓ ËÏÈÎ›·˜ ÌÂÁ·Ï‡ÙÂÚË˜ ÙˆÓ 5 ÂÙÒÓ (2,6-8,43). ∏ Û˘Á¯ÔÚ‹ÁËÛË ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ÙˆÓ ‰‡Ô ·˘ÙÒÓ Î·ÙË¶·È‰È·ÙÚÈÎ‹ 2006;69:417-424

ÁÔÚÈÒÓ Ê·ÚÌ¿ÎˆÓ ÌÂ ÙËÓ ›‰È· Û˘ÛÎÂ˘‹ Â›Ó·È ÙÔ˘Ï¿¯ÈÛÙÔÓ ÂÍ›ÛÔ˘ ·ÔÙÂÏÂÛÌ·ÙÈÎ‹ Î·È ·ÛÊ·Ï‹˜ ÌÂ ÙË ‰È·‰Ô¯ÈÎ‹ ¯ÔÚ‹ÁËÛ‹ ÙÔ˘˜ ÌÂ ‰‡Ô ‰È·ÊÔÚÂÙÈÎ¤˜ Û˘ÛÎÂ˘¤˜. √ ·ÚÈıÌfi˜ ÙˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ ÛÙ· ·È‰È¿ Â›Ó·È ÂÚÈÔÚÈÛÌ¤ÓÔ˜ ÛÂ Û¯¤ÛË ÌÂ ÂÎÂ›ÓÔÓ ÙˆÓ ÂÓËÏ›ÎˆÓ. øÛÙfiÛÔ, ÛÙËÓ ÏÂÈÔÓfiÙËÙ¿ ÙÔ˘˜ Î·È ÔÈ ·È‰È·ÙÚÈÎ¤˜ ÌÂÏ¤ÙÂ˜ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ÌÂÁ·Ï‡ÙÂÚË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ∂ÈÛ∫™ Î·È ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÙË ÌÔÓÔıÂÚ·Â›· ÌÂ ∂ÈÛ∫™, ÂÓÒ ÔÈ ‰ÈÂıÓÂ›˜ ÔÌÔÊˆÓ›Â˜ ÙÔÓ Û˘ÓÈÛÙÔ‡Ó. ∞·ÈÙÂ›Ù·È ÂÚ·ÈÙ¤Úˆ ¤ÚÂ˘Ó· ÁÈ· ÙÔÓ ·ÎÚÈ‚‹ ÚfiÏÔ ÙˆÓ Û˘Ó‰˘·ÛÌÒÓ ÛÂ ËÏÈÎ›Â˜ ÌÈÎÚfiÙÂÚÂ˜ ÙˆÓ 12 ÂÙÒÓ.

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∞ÓÙÈÊÏÂÁÌÔÓÒ‰Ë˜ ·ÁˆÁ‹ ˘ÔÙÚÔÈ¿˙ÔÓÙÔ˜ Û˘ÚÈÁÌÔ‡ ÛÙ· ¤ÓÙÂ ÚÒÙ· ¯ÚﬁÓÈ· ÙË˜ ˙ˆ‹˜ ª. B. ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜1, º. ∫˘Ú‚·Û›ÏË˜2, π. N. ∆Û·Ó¿Î·˜2

¶ÂÚ›ÏË„Ë: ∆· ‚Ú¤ÊË Î·È Ù· ·È‰È¿ ÙË˜ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ ÌÂ ˘ÔÙÚÔÈ¿˙ÔÓÙ· Û˘ÚÈÁÌfi ·ÔÙÂÏÔ‡Ó Î·ıËÌÂÚÈÓfi ÎÏÈÓÈÎfi Úfi‚ÏËÌ·. ™ÙËÓ ÏÂÈÔÓfiÙËÙ¿ ÙÔ˘˜ Ù· ·È‰È¿ ·˘Ù¿ ·‡Ô˘Ó Ó· ÂÎ‰ËÏÒÓÔ˘Ó Û˘ÚÈÁÌfi ÛÂ ÌÂÁ·Ï‡ÙÂÚË ËÏÈÎ›· Î·È ıÂˆÚÂ›Ù·È fiÙÈ Û˘ÓÈÛÙÔ‡Ó ‰È·ÊÔÚÂÙÈÎfi ÎÏÈÓÈÎfi Û‡Ó‰ÚÔÌÔ ·fi ÙÔ ¿ÛıÌ·. ™ÙËÓ ÎÏÈÓÈÎ‹ Ú¿ÍË ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È ÌÂ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ·ÓÙÈ·ÛıÌ·ÙÈÎ‹ ·ÁˆÁ‹, Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙË˜ ÔÔ›·˜ ÔÈÎ›ÏÏÂÈ. ∆· ÂÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ (∫™) Û˘ÓÈÛÙÔ‡Ó ÙËÓ Ï¤ÔÓ ·ÔÙÂÏÂÛÌ·ÙÈÎ‹ ·ÁˆÁ‹ Î·È Ê·›ÓÂÙ·È fiÙÈ ‚ÔËıÔ‡Ó È‰È·›ÙÂÚ· Ù· ‚Ú¤ÊË Î·È Ù· Ó‹È· ÌÂ ‰È·ÏÂ›ÔÓÙ· Û˘ÚÈÁÌfi Î·È ·ÙÔÈÎfi ˘fiÛÙÚˆÌ· (ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ¿ÛıÌ·ÙÔ˜, ÈÛÙÔÚÈÎfi ‰È·ÁÓˆÛÌ¤ÓÔ˘ ÂÎ˙¤Ì·ÙÔ˜ ‹/Î·È ·ÏÏÂÚÁÈÎ‹˜ ÚÈÓ›ÙÈ‰·˜, ˘„ËÏ‹ ÔÏÈÎ‹ IgE, ËˆÛÈÓÔÊÈÏ›·) Î·ıÒ˜ Î·È ÂÎÂ›Ó· Ô˘ ÂÎ‰ËÏÒÓÔ˘Ó Â›ÌÔÓ· Û˘ÌÙÒÌ·Ù·, ÂÓÒ Ë Ì·ÎÚÔ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛ‹ ÙÔ˘˜ Â›Ó·È ·ÛÊ·Ï‹˜ ÛÂ ¯·ÌËÏ¤˜ ‰fiÛÂÈ˜. ¶ÚfiÛÊ·ÙÂ˜ Î·Ï¿ Û¯Â‰È·ÛÌ¤ÓÂ˜ ÌÂÏ¤ÙÂ˜ ÛÂ ·È‰È¿ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Ë ÌÔÓÙÂÏÔ˘Î¿ÛÙË Â›Ó·È ·ÛÊ·Ï‹˜ Î·È ·ÔÙÂÏÂÛÌ·ÙÈÎ‹ ÛÂ Ì·ÎÚÔ¯ÚfiÓÈ· Û˘Á¯ÔÚ‹ÁËÛË ÌÂ Ù· ÂÈÛÓÂfiÌÂÓ· ∫™ (Û˘Ó‰˘·ÛÌ¤ÓË ıÂÚ·Â›·), ÂÓÒ ÌÔÚÂ› Ó· ·Ô‚Â› ·ÔÙÂÏÂÛÌ·ÙÈÎ‹ Î·È ˆ˜ ÌÔÓÔıÂÚ·Â›· ÛÙÔÓ ‰È·ÏÂ›ÔÓÙ· ÈÔÁÂÓ‹ Û˘ÚÈÁÌfi ÙË˜ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜. √È Í·Óı›ÓÂ˜ ·ÔÙÂÏÔ‡Ó ÂÓ·ÏÏ·ÎÙÈÎ‹, ÚfiÛıÂÙË ÛÙ· ÂÈÛÓÂfiÌÂÓ· ∫™ ıÂÚ·Â›·, fiÌˆ˜, ··ÈÙÂ›Ù·È ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ÂÈ¤‰ˆÓ ıÂÔÊ˘ÏÏ›ÓË˜ ÛÙÔÓ ÔÚfi ÙˆÓ ·ÛıÂÓÒÓ. ªÂÁ¿ÏË ÚÔÔÙÈÎ‹ ÌÂÏ¤ÙË Î·ıÒ˜ Î·È ÌÂÙ·-·Ó¿Ï˘ÛË ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ Ô˘ Û˘Ó¤ÎÚÈÓ·Ó ÙÈ˜ ¯ÚˆÌfiÓÂ˜ ÌÂ Ù· ÂÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ ·ÌÊÈÛ‚‹ÙËÛ·Ó ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ¿ ÙÔ˘˜ ÛÙÔÓ Â·ÚÎ‹ ¤ÏÂÁ¯Ô ÙÔ˘ ¿ÛıÌ·ÙÔ˜. øÛÙfiÛÔ, ·˘Ù¤˜ ‰È·ÙËÚÔ‡Ó ÙÔÓ ÚfiÏÔ ÙÔ˘˜, ·Ó Î·È ·Ô‰˘Ó·ÌˆÌ¤ÓÔ, ˆ˜ ÂÓ·ÏÏ·ÎÙÈÎ‹ ÌÔÓÔıÂÚ·Â›· ÛÙÔ ‹ÈÔ Â›ÌÔÓÔ ¿ÛıÌ· ÙË˜ ·È‰ÈÎ‹˜ ËÏÈÎ›·˜.

1 ¶·È‰ÔÓÂ˘ÌÔÓÔÏÔÁÈÎ‹ ªÔÓ¿‰·, ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ 2 ¶·È‰ÔÓÂ˘ÌÔÓÔÏÔÁÈÎ‹ ªÔÓ¿‰·, °/¶¢, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌÂ›Ô, ∞ÚÈÛÙÔÙ¤ÏÂÈÔ ¶·ÓÂÈÛÙ‹ÌÈÔ £ÂÛÛ·ÏÔÓ›ÎË˜. AÏÏËÏÔÁÚ·Ê›·: ªÈ¯¿ÏË˜ ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ ∆.∫. 26504, ƒ›Ô ∂-mail: manthra@otenet.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 28-11-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 19-09-2006

§¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ∞ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎ¿, ¿ÛıÌ·, ÂÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹, Ó‹È·, Í·Óı›ÓÂ˜, Û˘ÚÈÁÌfi˜, ¯ÚˆÌfiÓÂ˜.

Anti-inflammatory therapy of recurrent wheezing during the first five years of life M. B. Anthracopoulos1, F. Kyrvassilis2, J. N. Tsanakas2

Abstract: Recurrent wheezing is a common clinical problem in infants and toddlers. Although most of these children stop wheezing later in childhood, and their symptoms most probably constitute a clinical syndrome different from asthma, they seem to respond -albeit variably- to anti-inflammatory treatment for asthma. Inhaled corticosteroids (CS) have proved to be helpful, particularly in those infants and toddlers with atopic background (i.e. positive family history of asthma, history of physician-diagnosed eczema and/or allergic rhinitis, increased total IgE levels and blood eosinophils) and in those with persistent symptoms. Long-term inhalation of CS at low doses has proved to be safe in young children. Recent well-designed clinical studies have shown that montelukast constitutes a safe and effective addon therapy in infants and toddlers, and may improve symptoms when used as monotherapy. Xanthenes constitute an alternative additive to inhaled CS, combination therapy, but careful monitoring of serum levels is needed. A large prospective study and a meta-analysis, which compared inhaled CS with cromones, questioned the efficacy of cromones in the control of persistent asthma; however, these drugs maintain their role (albeit weakened) as an alternative monotherapy in mild persistent asthma.

1 Unit of Paediatric Pneumonology, Paediatric Clinic, University of Patras 2 Unit of Paediatric Pneumonology, 3rd Paediatric Clinic, Ippokratio Hospital, Aristotle University of Thessaloniki Correspondence: Michael Anthracopoulos Paediatric Clinic, University of Patras 26504, Rio ∂-mail: manthra@otenet.gr Date of submission: 28-11-2005 Date of approval: 19-09-2006

Key words: Anti-leukotriene agents, asthma, cromones, infants, inhaled corticosteroids, wheezing, xanthenes.

¶·È‰È·ÙÚÈÎ‹ 2006;69:425-431

426

ª. B. ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜ Î·È Û˘Ó.

™˘ÓÙÔÌÔÁÚ·Ê›Â˜: ∫™: ∫ÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ ¡√: ªÔÓÔÍÂ›‰ÈÔ ÙÔ˘ ·˙ÒÙÔ˘ ∆∂¶: ∆Ì‹Ì· ∂ÂÈÁﬁÓÙˆÓ ¶ÂÚÈÛÙ·ÙÈÎÒÓ

∂ÈÛ·ÁˆÁ‹ √ ˘ÔÙÚÔÈ¿˙ˆÓ Û˘ÚÈÁÌfi˜, È‰›ˆ˜ ÌÂÙ¿ ·fi ÈÔÁÂÓ‹ ÏÔ›ÌˆÍË ÙÔ˘ ·Ó·ÓÂ˘ÛÙÈÎÔ‡, ·ÔÙÂÏÂ› Û˘¯Ófi Û‡ÌÙˆÌ· Î·Ù¿ ÙË ‚ÚÂÊÈÎ‹ Î·È ÙËÓ ÚÔÛ¯ÔÏÈÎ‹ ËÏÈÎ›· (1,2). ∆· ÂÚÈÛÛfiÙÂÚ· ·fi ·˘Ù¿ Ù· ‚Ú¤ÊË Î·È ÌÈÎÚ¿ ·È‰È¿ ·‡Ô˘Ó Ó· ÂÎ‰ËÏÒÓÔ˘Ó Û˘ÚÈÁÌfi ÛÂ ÌÂÁ·Ï‡ÙÂÚË ËÏÈÎ›·, fiÌˆ˜, ÛÂ ÌÂÚÈÎ¿ Ù· Û˘ÌÙÒÌ·Ù· ·Ú·Ì¤ÓÔ˘Ó Î·È ÙÂÏÈÎ¿ ‰È·ÁÈÁÓÒÛÎÔÓÙ·È ˆ˜ ·ÛıÌ·ÙÈÎ¿. ∞fi ÙËÓ ¿ÏÏË ÌÂÚÈ¿, ¤¯ÂÈ ·Ô‰ÂÈ¯ıÂ› fiÙÈ ÙÔ ¿ÛıÌ· Û˘Ó‹ıˆ˜ ÂÎ‰ËÏÒÓÂÙ·È ÓˆÚ›˜ Î·Ù¿ ÙËÓ ·È‰ÈÎ‹ ËÏÈÎ›· (3), ÂÓÒ Ë ÚÒÈÌË ·Ú¤Ì‚·ÛË ÌÂ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ·ÁˆÁ‹ Â›Ó·È Èı·Ófi -¿ÓÙˆ˜ Î¿ıÂ ¿ÏÏÔ ·Ú¿ ÂÈ‚Â‚·ÈˆÌ¤ÓÔ- fiÙÈ ÂËÚÂ¿˙ÂÈ ÙË Ê˘ÛÈÎ‹ ÔÚÂ›· ÙË˜ ÓfiÛÔ˘ Î·È ÚÔÏ·Ì‚¿ÓÂÈ ÙË ÌË ·Ó·ÛÙÚ¤„ÈÌË ‚ÚÔÁ¯ÔÛÙ¤ÓˆÛË (4). ¢˘ÛÙ˘¯Ò˜, ·Ú¿ ÙÈ˜ ‰È·ÊÔÚ¤˜ ÛÙËÓ ÚfiÁÓˆÛË, ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈÎ‹ ·ÏÏËÏÔÂÈÎ¿Ï˘„Ë ÛÙËÓ ÎÏÈÓÈÎ‹ ÚÔ‚ÔÏ‹ ÙˆÓ ‰‡Ô ·Ú·¿Óˆ “Û˘Ó‰ÚfiÌˆÓ Û˘ÚÈÁÌÔ‡” ÙˆÓ ÌÈÎÚÒÓ ·È‰ÈÒÓ ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‚Â‚·ÈfiÙËÙ· Î·È ÙË Û‡Á¯˘ÛË ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛ‹ ÙÔ˘˜ (5-7). ¶Ú¿ÁÌ·ÙÈ, Î·Ù¿ ÙËÓ ÚÔÛ¯ÔÏÈÎ‹ ËÏÈÎ›·, ÙÈ˜ ÂÚÈÛÛfiÙÂÚÂ˜ ÊÔÚ¤˜ Ë ·ÛıÌ·ÙÈÎ‹ Û˘ÌÙˆÌ·ÙÔÏÔÁ›· ÂÎ‰ËÏÒÓÂÙ·È ÌÂ ‰È·ÎÚÈÙ¿ ÌÂÙ·Í‡ ÙÔ˘˜ ÂÂÈÛfi‰È· (‹È·, Ì¤ÙÚÈ· ‹ ÛÔ‚·Ú¿) Î·È ·Û˘ÌÙˆÌ·ÙÈÎ¿ ÌÂÛÔ‰È·ÛÙ‹Ì·Ù· ÌÂ Û˘ÓËı¤ÛÙÂÚÔ ÂÎÏ˘ÙÈÎfi ·Ú¿ÁÔÓÙ· ÙÈ˜ ÈÔÁÂÓÂ›˜ ÏÔÈÌÒÍÂÈ˜ ÙÔ˘ ·Ó·ÓÂ˘ÛÙÈÎÔ‡. ∏ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË Ú·ÁÌ·ÙÂ‡ÂÙ·È ÂÓ Û˘ÓÙÔÌ›· ÙË ¯Ú‹ÛË ÙˆÓ ‰È·ÊfiÚˆÓ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ Ê·ÚÌ¿ÎˆÓ ÛÙÔÓ ˘ÔÙÚÔÈ¿˙ÔÓÙ· Û˘ÚÈÁÌfi Î·Ù¿ Ù· ¤ÓÙÂ ÚÒÙ· ¯ÚfiÓÈ· ÙË˜ ˙ˆ‹˜.

ª·ÎÚÔ¯ÚfiÓÈ· ·ÓÙÈ·ÛıÌ·ÙÈÎ‹ ·ÁˆÁ‹ ÛÂ ËÏÈÎ›· <5 ÂÙÒÓ ∏ ÚfiÛÊ·ÙË ÂıÓÈÎ‹ ÔÌÔÊˆÓ›· ÙˆÓ ∏¶∞ ÁÈ· ÙË ‰È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ¿ÛıÌ·ÙÔ˜ (8), ‚·ÛÈ˙fiÌÂÓË ÛÙËÓ ÙÚ¤¯Ô˘Û· ÎÏÈÓÈÎ‹ ÂÌÂÈÚ›· Î·È ÛÙ· Â˘Ú‹Ì·Ù· ÙË˜ ÚÔÔÙÈÎ‹˜ ÌÂÏ¤ÙË˜ ÙË˜ Tucson (9), ¤¯ÂÈ ı¤ÛÂÈ Ù· ·ÎfiÏÔ˘ı· ÎÚÈÙ‹ÚÈ· ÚÔÎÂÈÌ¤ÓÔ˘ Ó· ¯ÔÚËÁËıÂ› Ì·ÎÚÔ¯ÚfiÓÈ· ·ÓÙÈ·ÛıÌ·ÙÈÎ‹ ·ÁˆÁ‹ ÛÂ ·È‰È¿ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜: 1. µÚ¤ÊË Î·È ÌÈÎÚ¿ ·È‰È¿ Ô˘ ¯ÚÂÈ¿˙ÔÓÙ·È ¶·È‰È·ÙÚÈÎ‹ 2006;69:425-431

Û˘ÌÙˆÌ·ÙÈÎ‹ ·ÁˆÁ‹ ÌÂ ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ¿ Û˘¯ÓfiÙÂÚ· ·fi ‰‡Ô ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·. 2. µÚ¤ÊË Î·È ÌÈÎÚ¿ ·È‰È¿ Ô˘ ÂÎ‰ËÏÒÓÔ˘Ó ÂÂÈÛfi‰È· ÛÔ‚·ÚÒÓ ·ÚÔÍ˘ÛÌÒÓ (Ô˘ ··ÈÙÔ‡Ó ÂÈÛÓÂfiÌÂÓÔ ‚2-‰ÈÂÁ¤ÚÙË Û˘¯ÓfiÙÂÚ· ·fi Î¿ıÂ 4 ÒÚÂ˜ ÁÈ· ¤Ó· 24ˆÚÔ) Û˘¯ÓfiÙÂÚ· ·fi Î¿ıÂ 6 Â‚‰ÔÌ¿‰Â˜. 3. µÚ¤ÊË Î·È ÌÈÎÚ¿ ·È‰È¿ Ô˘ ¤¯Ô˘Ó ÂÎ‰ËÏÒÛÂÈ ÂÚÈÛÛfiÙÂÚ· ·fi ÙÚ›· ÂÂÈÛfi‰È· Û˘ÚÈÁÌÔ‡ ‰È¿ÚÎÂÈ·˜ >24ÒÚÔ˘ ÌÂ ‰È·Ù·Ú·¯‹ ÙÔ˘ ‡ÓÔ˘ Î·Ù¿ ÙÔ ÙÂÏÂ˘Ù·›Ô ¤ÙÔ˜ Î·È ¤¯Ô˘Ó ·˘ÍËÌ¤ÓÔ Î›Ó‰˘ÓÔ Â›ÌÔÓÔ˘ ¿ÛıÌ·ÙÔ˜. ∞˘ÍËÌ¤ÓÔ˘ ÎÈÓ‰‡ÓÔ˘ ıÂˆÚÔ‡ÓÙ·È Ù· ‚Ú¤ÊË Î·È ÌÈÎÚ¿ ·È‰È¿ ÌÂ: (·) ÈÛÙÔÚÈÎfi ¿ÛıÌ·ÙÔ˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ ÂÓfi˜ ·fi ÙÔ˘˜ ÁÔÓÂ›˜, (‚) È·ÙÚÈÎ‹ ‰È¿ÁÓˆÛË ·ÙÔÈÎ‹˜ ‰ÂÚÌ·Ù›ÙÈ‰·˜ ‹ (Á) ‰‡Ô ·fi Ù· ·ÎfiÏÔ˘ı·: (i) ‰È·ÁÓˆÛÌ¤ÓË ·ÏÏÂÚÁÈÎ‹ ÚÈÓ›ÙÈ‰·, (ii) ËˆÛÈÓfiÊÈÏ· ≥5% ÛÙÔ ÂÚÈÊÂÚÈÎfi ·›Ì·, (iii) Û˘ÚÈÁÌfi ¯ˆÚ›˜ ÈÔÁÂÓ‹ ÏÔ›ÌˆÍË. ∏ ÎÏÈÓÈÎ‹ ·¿ÓÙËÛË ÛÙË ¯ÔÚ‹ÁËÛË ÂÈÛÓÂfiÌÂÓˆÓ ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎÒÓ Î·È ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ Ê·ÚÌ¿ÎˆÓ Û˘¯Ó¿ ·Ô‚·›ÓÂÈ ÙÔ Ï¤ÔÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfi ÎÚÈÙ‹ÚÈÔ ÁÈ· ÙË Ï‹„Ë ÙˆÓ ıÂÚ·Â˘ÙÈÎÒÓ ·ÔÊ¿ÛÂˆÓ (8,10).

∂ÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ (∫™) ∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙË˜ Ì·ÎÚÔ¯ÚfiÓÈ·˜ Ú˘ıÌÈÛÙÈÎ‹˜ ·ÁˆÁ‹˜ ÌÂ ÂÈÛÓÂfiÌÂÓ· ∫™ ÛÂ ‚Ú¤ÊË Î·È ·È‰È¿ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ ¤¯ÂÈ ‰ÂÈ¯ıÂ› ÛÂ ÛÂÈÚ¿ ÌÂÏÂÙÒÓ Ô˘ ¤¯Ô˘Ó ·ÍÈÔÏÔÁËıÂ› ÛÂ ‰‡Ô Û˘ÛÙËÌ·ÙÈÎ¤˜ ·Ó·ÛÎÔ‹ÛÂÈ˜ (11,12). ™ÙËÓ ÚÒÙË ÂÚÈÂÏ‹ÊıËÛ·Ó 24 Ù˘¯·ÈÔÔÈËÌ¤ÓÂ˜ ‰ÈÏ¤˜ Ù˘ÊÏ¤˜ ÌÂÏ¤ÙÂ˜ ÌÂ ÔÌ¿‰· ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (Û˘ÓÔÏÈÎ¿ 1087 ·ÛıÂÓÂ›˜), ·fi ÙÈ˜ ÔÔ›Â˜ ÔÈ 10 ·ÊÔÚÔ‡Û·Ó ÛÂ ·È‰È¿ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ (Û˘ÓÔÏÈÎ¿ 377 ·ÛıÂÓÂ›˜) (11). ∏ ·Ó·ÛÎfiËÛË ·˘Ù‹ ¤‰ÂÈÍÂ ¯·ÌËÏfiÙÂÚË ‚·ıÌÔÏÔÁ›· (score) Û˘ÌÙˆÌ¿ÙˆÓ, ¯Ú‹ÛË ‚2-·ÁˆÓÈÛÙÒÓ Î·È per os ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ, Î·È ˘„ËÏfiÙÂÚÂ˜ ÙÈÌ¤˜ Ì¤ÁÈÛÙË˜ ÂÎÓÂ˘ÛÙÈÎ‹˜ ÚÔ‹˜ (PEF) ÛÙ· ·È‰È¿ Ô˘ Ï¿Ì‚·Ó·Ó ÂÈÛÓÂfiÌÂÓ· ∫™, ·Ó Î·È Ù· ÛÙÔÈ¯Â›· ÁÈ· Ù· ÌÈÎÚfiÙÂÚ· ·È‰È¿ ‹Ù·Ó ÂÏÏÈ‹ ÛÂ fi,ÙÈ ·ÊÔÚ¿ ÙÈ˜ ÂÈÛ·ÁˆÁ¤˜ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô. ∏ ‰Â‡ÙÂÚË Û˘ÛÙËÌ·ÙÈÎ‹ ·Ó·ÛÎfiËÛË (12) ÂÚÈ¤Ï·‚Â Ù¤ÛÛÂÚÈ˜ ÂÈÏ¤ÔÓ ÌÂÏ¤ÙÂ˜ ÌÂ 861 ·ÛıÂÓÂ›˜ ËÏÈÎ›·˜ 3 ÌËÓÒÓ ¤ˆ˜ 8 ÂÙÒÓ (13-16), ÔÈ ÔÔ›Â˜ Î·Ù¤ÏËÁ·Ó ÛÂ ·Ó¿ÏÔÁ· Û˘ÌÂÚ¿ÛÌ·Ù·. ªÂÙ¿ ·fi Û˘ÛÙËÌ·ÙÈÎ‹ ¤ÚÂ˘Ó· ÙË˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ Î·Ù¿ ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË ‚Ú¤ıËÎ·Ó 10 ÂÈÏ¤ÔÓ Ù˘¯·ÈÔÔÈËÌ¤ÓÂ˜ ‰ÈÏ¤˜ Ù˘ÊÏ¤˜ ÌÂÏ¤ÙÂ˜ ÌÂ ÔÌ¿‰·

427

∞ÓÙÈÌÂÙÒÈÛË Û˘ÚÈÁÌÔ‡ ‚ÚÂÊÒÓ Î·È ÓË›ˆÓ

ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ Ô˘ ÂÍÂÙ¿˙Ô˘Ó ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ∫™ ÛÂ ‚Ú¤ÊË Î·È Ó‹È· ÌÂ Â›ÌÔÓÔ ‹ ˘ÔÙÚÔÈ¿˙ÔÓÙ· Û˘ÚÈÁÌfi (ÂÚ›Ô˘ 2000 ·ÛıÂÓÂ›˜) (17-26). ªÂÁ¿ÏË ÌÂÏ¤ÙË 528 ·È‰ÈÒÓ ËÏÈÎ›·˜ 4-11 ÂÙÒÓ Ô˘ Û˘ÁÎÚ›ÓÂÈ ‰‡Ô ‰fiÛÂÈ˜ ÊÏÔ˘ÙÈÎ·˙fiÓË˜ (200 ¤Ó·ÓÙÈ 400 Ìg ËÌÂÚËÛ›ˆ˜), ‰ÂÓ ÂÚÈÏ·Ì‚¿ÓÂÈ ÔÌ¿‰· ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ Î·È ‰ÂÓ ·Ú¤¯ÂÈ ‰Â‰ÔÌ¤Ó· ÁÈ· ÙÔÓ ·ÚÈıÌfi ÙˆÓ ·È‰ÈÒÓ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ Ô˘ ÂÚÈÂÏ‹ÊıËÛ·Ó ‹ ÁÈ· Ù· ·ÔÙÂÏ¤ÛÌ·Ù· ÙË˜ ·ÁˆÁ‹˜ ÛÙËÓ ËÏÈÎÈ·Î‹ ·˘Ù‹ ÔÌ¿‰· (27). √È ÂÚÈÛÛfiÙÂÚÂ˜ ·fi ÙÈ˜ ÌÂÏ¤ÙÂ˜ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ¯ÔÚ‹ÁËÛË˜ ÂÈÛÓÂfiÌÂÓˆÓ ∫™ ‰Â›¯ÓÔ˘Ó ‚ÂÏÙ›ˆÛË ‰È·ÊfiÚˆÓ ÎÏÈÓÈÎÒÓ ‰ÂÈÎÙÒÓ Î·ıÒ˜ Î·È ÔÚÈÛÌ¤ÓˆÓ ‰ÂÈÎÙÒÓ (·Ó Î·È fi¯È fiÏˆÓ) ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ ·ÛıÂÓÒÓ (13-25). øÛÙfiÛÔ, ÌÈÎÚ‹ ÌÂÏ¤ÙË 31 ·È‰ÈÒÓ Î¿Ùˆ ÙˆÓ 2 ÂÙÒÓ ‰ÂÓ ¤‰ÂÈÍÂ ‚ÂÏÙ›ˆÛË ÙˆÓ ÎÏÈÓÈÎÒÓ ‰ÂÈÎÙÒÓ ÛÂ ·ÛıÂÓÂ›˜ Ô˘ ¤Ï·‚·Ó 200 Ìg ÂÈÛÓÂfiÌÂÓË˜ ÌÂÎÏÔÌÂı·˙fiÓË˜ Ì·˙› ÌÂ Û·Ï‚Ô˘Ù·ÌfiÏË ‰‡Ô ÊÔÚ¤˜ ÙËÓ ËÌ¤Ú· Â› 8 Â‚‰ÔÌ¿‰Â˜ ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÙËÓ ÔÌ¿‰· ÂÏ¤Á¯Ô˘ (¯ÔÚ‹ÁËÛË ÌfiÓÔ Û·Ï‚Ô˘Ù·ÌfiÏË˜) (23), ÂÓÒ ÌÂÏ¤ÙË 65 ‚ÚÂÊÒÓ (Ì¤ÛË ËÏÈÎ›· 11,3 Ì‹ÓÂ˜) ‰ÂÓ ¤‰ÂÈÍÂ ‚ÂÏÙ›ˆÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÂÎÂ›ÓˆÓ Ô˘ ¤Ï·‚·Ó 200 Ìg ÊÏÔ˘ÙÈÎ·˙fiÓË˜ ËÌÂÚËÛ›ˆ˜ Â› 3 Ì‹ÓÂ˜, ¤Ó·ÓÙÈ ÙË˜ ÔÌ¿‰·˜ Ô˘ ¤Ï·‚Â ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (24). ™Â ÚfiÛÊ·ÙË ÔÏ˘ÎÂÓÙÚÈÎ‹ ÌÂÏ¤ÙË ·fi ÙÈ˜ ∏¶∞ (n=285) Ô˘ ‰ËÌÔÛÈÂ‡ıËÎÂ ÛÙÔ New England Journal of Medicine (25), ‰Â›¯ıËÎÂ fiÙÈ ·È‰È¿ 2-3 ÂÙÒÓ Ô˘ ·Ó‹Î·Ó ÛÂ ÔÌ¿‰· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ¿ÛıÌ· Î·È ¤Ï·‚·Ó 20 Ìg ÊÏÔ˘ÙÈÎ·˙fiÓË˜ ËÌÂÚËÛ›ˆ˜ Â› 2 ¤ÙË, ÂÎ‰‹ÏˆÛ·Ó ÏÈÁfiÙÂÚ· ·ÛıÌ·ÙÈÎ¿ Û˘ÌÙÒÌ·Ù· Î·È ·ÚÔÍ˘ÛÌÔ‡˜ ÙË˜ ÓfiÛÔ˘ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ·ÁˆÁ‹˜ ·fi ÂÎÂ›Ó· Ô˘ ¤Ï·‚·Ó ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ. ∂›ÛË˜, Ë ÔÌ¿‰· ÙË˜ ÊÏÔ˘ÙÈÎ·˙fiÓË˜ ·ÚÔ˘Û›·ÛÂ ¯·ÌËÏfiÙÂÚÂ˜ ·ÓÙÈÛÙ¿ÛÂÈ˜ ·ÂÚ·ÁˆÁÒÓ (Ì¤ÙÚËÛË ÌÂ Ù·Ï·ÓÙˆÛÈÌÂÙÚ›·) ·fi ÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. øÛÙfiÛÔ, ·Ú¿ ÙÔÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfi ¤ÏÂÁ¯Ô ÙˆÓ ·ÛıÌ·ÙÈÎÒÓ ÂÎ‰ËÏÒÛÂˆÓ, Ë ÊÏÔ˘ÙÈÎ·˙fiÓË ‰ÂÓ ÌÂÙ¤‚·ÏÂ ÙË Ê˘ÛÈÎ‹ ÔÚÂ›· ÙË˜ ÓfiÛÔ˘, fiˆ˜ ·Ô‰Â›¯ıËÎÂ ·fi ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ·È‰ÈÒÓ ¯ˆÚ›˜ Ê·ÚÌ·ÎÂ˘ÙÈÎ‹ ·ÁˆÁ‹ ÁÈ· ¤Ó· ÂÈÏ¤ÔÓ ¤ÙÔ˜. ™Â ‰Â‡ÙÂÚË ‰ÈÏ‹ Ù˘ÊÏ‹ Ù˘¯·ÈÔÔÈËÌ¤ÓË ÌÂÏ¤ÙË ÌÂ ÔÌ¿‰· ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ Ô˘ ‰È‹ÚÎÂÛÂ 3 ¤ÙË Î·È ‰ËÌÔÛÈÂ‡ıËÎÂ ÛÙÔ ›‰ÈÔ ÙÂ‡¯Ô˜ ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡, ÔÈ Bisgaard Î·È Û˘Ó (26) ÌÂÏ¤ÙËÛ·Ó ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙË˜ Î·Ù’ Â›ÎÏËÛÈÓ ¯ÔÚ‹ÁËÛË˜ 400 Ìg ‚Ô˘‰ÂÛÔÓ›‰Ë˜ (¤Ó·ÚÍË ·Áˆ-

Á‹˜: ÙÚ›· 24ˆÚ· ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË ÙˆÓ ÂÂÈÛÔ‰›ˆÓ, ‰È¿ÚÎÂÈ· ·ÁˆÁ‹˜: ‰‡Ô Â‚‰ÔÌ¿‰Â˜ ·Ó¿ ÂÂÈÛfi‰ÈÔ) ÛÂ ‚Ú¤ÊË ÌÂ ·ÛıÌ·ÙÈÎ‹ Û˘ÌÙˆÌ·ÙÔÏÔÁ›· ÌÂÙ¿ ÙÔÓ ÚÒÙÔ Ì‹Ó· ˙ˆ‹˜. ¢Â›¯ıËÎÂ fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÙË˜ ‚Ô˘‰ÂÛÔÓ›‰Ë˜ ‰ÂÓ Â›¯Â Î·Ì›· Â›‰Ú·ÛË ‚Ú·¯˘ÚfiıÂÛÌ· ÛÙ· ·ÛıÌ·ÙÈÎ¿ Û˘ÌÙÒÌ·Ù· ÙˆÓ ·È‰ÈÒÓ Î·È ‰ÂÓ Â¤‰Ú·ÛÂ ÛÙËÓ ÂÍ¤ÏÈÍË ÙË˜ ‰È·ÏÂ›Ô˘Û·˜ Û˘ÌÙˆÌ·ÙÔÏÔÁ›·˜ ÛÂ Â›ÌÔÓÔ ¿ÛıÌ·. √È ‰‡Ô ·˘Ù¤˜ ÌÂÏ¤ÙÂ˜ (25,26), ÂÎÙfi˜ ·fi ÙÈ˜ ÏËÚÔÊÔÚ›Â˜ Ô˘ ·Ú¤¯Ô˘Ó ÛÂ fi,ÙÈ ·ÊÔÚ¿ ÙÔÓ ¤ÏÂÁ¯Ô (‹ ÌË) ÙˆÓ ·ÛıÌ·ÙÈÎÒÓ Û˘ÌÙˆÌ¿ÙˆÓ ·fi Ù· ‰È¿ÊÔÚ· ıÂÚ·Â˘ÙÈÎ¿ Û¯‹Ì·Ù· ÂÈÛÓÂfiÌÂÓˆÓ ∫™, ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ¿Ô„Ë fiÙÈ Ù· Ê¿ÚÌ·Î· ·˘Ù¿, ·ÎfiÌË Î·È ÛÂ ÚÒÈÌË ¯ÔÚ‹ÁËÛË, ‰ÂÓ ÌÂÙ·‚¿ÏÏÔ˘Ó ÙË Ê˘ÛÈÎ‹ ÔÚÂ›· ÙË˜ ÓfiÛÔ˘. ™Â ·Ó¿ÏÔÁ· Û˘ÌÂÚ¿ÛÌ·Ù· Â›¯Â Î·Ù·Ï‹ÍÂÈ Î·È Ë ÌÂÏ¤ÙË CAMP Ë ÔÔ›· ÂÚÈ¤Ï·‚Â ·È‰È¿ ÌÂÁ·Ï‡ÙÂÚË˜ ËÏÈÎ›·˜ (28). ¶·ÚfiÙÈ ‰ÂÓ ˘¿Ú¯Ô˘Ó ÌÂÁ¿ÏÂ˜ Ì·ÎÚÔ¯ÚfiÓÈÂ˜ ÌÂÏ¤ÙÂ˜ ‹ Û˘ÛÙËÌ·ÙÈÎ¤˜ ·Ó·ÛÎÔ‹ÛÂÈ˜ Ô˘ Ó· ‰ÈÂÚÂ˘ÓÔ‡Ó ÙË Û˘ÛÙËÌ·ÙÈÎ‹ ‰Ú¿ÛË ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ∫™ ÂÈ‰ÈÎ¿ ÛÂ ·È‰È¿ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜, ÔÚÈÛÌ¤ÓÂ˜ ÌÂÏ¤ÙÂ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ, ÙÔ˘Ï¿¯ÈÛÙÔÓ ÛÙÈ˜ ˘„ËÏfiÙÂÚÂ˜ ‰fiÛÂÈ˜, Ú¿ÁÌ·ÙÈ ˘Ê›ÛÙ·Ù·È Û˘ÛÙËÌ·ÙÈÎ‹ ‰Ú¿ÛË (19,29,30). ∂Í¿ÏÏÔ˘, Ë ‡·ÚÍË Û˘ÛÙËÌ·ÙÈÎ‹˜ ‰Ú¿ÛË˜ ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ∫™ ¤¯ÂÈ ‰ÂÈ¯ıÂ› ÛÂ ÌÂÏ¤ÙÂ˜ Î·È ÌÂÙ·-·Ó·Ï‡ÛÂÈ˜ ÌÂÁ·Ï‡ÙÂÚˆÓ ·È‰ÈÒÓ (31,32). ¶Ú¤ÂÈ ˆÛÙfiÛÔ Ó· ÙÔÓÈÛıÂ› fiÙÈ Ë ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë˜ ‰Ú¿ÛË ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ fiÛÔÓ ·ÊÔÚ¿ ÛÙÔ ·Ó·ÓÂ˘ÛÙÈÎfi Û‡ÛÙËÌ· Â›Ó·È ·Ó·ÌÊÈÛ‚‹ÙËÙË Î·È fiÙÈ, fiˆ˜ Û˘Ì‚·›ÓÂÈ ÌÂ Ù· ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿, ¤ÙÛÈ Î·È ÛÙ· Ó‹È·, Ù· ÂÈÛÓÂfiÌÂÓ· ∫™ ·ÔÙÂÏÔ‡Ó ÙË ıÂÚ·Â›· ÂÎÏÔÁ‹˜ ÛÂ fiÏ· Ù· ÛÙ¿‰È· ÙÔ˘ Â›ÌÔÓÔ˘ ¿ÛıÌ·ÙÔ˜, ÌfiÓ· ‹ ÛÂ Û˘Ó‰˘·ÛÌfi ÌÂ ¿ÏÏ· Ê¿ÚÌ·Î· (‚2·ÁˆÓÈÛÙ¤˜ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜, ·ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎ¿, ıÂÔÊ˘ÏÏ›ÓË) (8,10,33). ∂ÔÌ¤Óˆ˜, Ë “ÎÔÚÙÈÎÔÊÔ‚›·” ‰ÂÓ ‰ÈÎ·ÈÔÏÔÁÂ›Ù·È ÂÊfiÛÔÓ Ô ÁÈ·ÙÚfi˜ ‚Ú›ÛÎÂÙ·È ¿ÓÙ· ÛÂ ÂÁÚ‹ÁÔÚÛË ÚÔÎÂÈÌ¤ÓÔ˘ Ó· ÂÏ·ÙÙÒÛÂÈ ÙË ‰fiÛË ÛÙËÓ ÂÏ¿¯ÈÛÙË ··ÈÙÔ‡ÌÂÓË ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ÙÔ˘ ¿ÛıÌ·ÙÔ˜ (34-36). ∆ÔÓ›˙ÂÙ·È fiÙÈ Ë ¯ÔÚ‹ÁËÛË Ì·ÎÚÔ¯ÚfiÓÈ·˜ Ú˘ıÌÈÛÙÈÎ‹˜ ·ÁˆÁ‹˜ ÌÂ ÂÈÛÓÂfiÌÂÓ· ∫™ Î·Ù¿ ÙËÓ ÚÔÛ¯ÔÏÈÎ‹ ËÏÈÎ›· ÛÂ ‰fiÛË ˘„ËÏfiÙÂÚË ÙË˜ ÔÚÈ˙fiÌÂÓË˜ ·fi ÙÈ˜ ÔÌÔÊˆÓ›Â˜ ˆ˜ “¯·ÌËÏ‹˜” (¶›Ó·Î·˜ 1) Ú¤ÂÈ Ó· Û˘Ó·ÔÊ·Û›˙ÂÙ·È ¿ÓÙÔÙÂ ÌÂ ÙÔÓ ÂÈ‰ÈÎfi ÁÈ·ÙÚfi (8,10,33). ∆· ‰È·ÏÂ›ÔÓÙ· ÂÂÈÛfi‰È· Û˘ÚÈÁÌÔ‡ ÌÂÙ¿ ·fi ÈÔÁÂÓ‹ ÏÔ›ÌˆÍË ÛÂ ·ÛıÂÓÂ›˜ Ô˘ ‰ÂÓ ¤¯Ô˘Ó Î·Ó¤Ó· Û‡ÌÙˆÌ· Î·Ù¿ Ù· ÌÂÛÔ‰È·ÛÙ‹Ì·Ù·, ·ÔÙÂÏÔ‡Ó È‰È·›ÙÂÚÔ Úfi‚ÏËÌ·, ÛÙËÓ ¶·È‰È·ÙÚÈÎ‹ 2006;69:425-431

428

ª. B. ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜ Î·È Û˘Ó.

¶›Ó·Î·˜ 1. ¢È·‚¿ıÌÈÛË ‰ÔÛÔÏÔÁ›·˜ ÂÈÛÓÂfiÌÂÓˆÓ ∫™ ÛÂ ·È‰È¿ <12 ÂÙÒÓ (10)* º·ÚÌ·ÎÂ˘ÙÈÎ‹ Ô˘Û›· (Ìg)** µÔ˘‰ÂÛÔÓ›‰Ë (DPI) µÔ˘‰ÂÛÔÓ›‰Ë (neb. suspension) ªÔÌÂÙ·˙fiÓË (DPI)*** ªÂÎÏÔÌÂı·˙fiÓË (pMDI-CFC) ªÂÎÏÔÌÂı·˙fiÓË (pMDI-HFA) ºÏÔ˘ÙÈÎ·˙fiÓË (pMDI-CFC, DPI)

Ã·ÌËÏ‹ ‰ﬁÛË

ª¤ÙÚÈ· ‰ﬁÛË

À„ËÏ‹ ‰ﬁÛË

100-200 0,25-0,5 mg 100-250 50-200 100-200

200-600 0,5-1,0 mg 250-500 200-400 200-400

>600 >1,0 mg >500 >400 >400

* √È ·Ó·ÁÚ·ÊfiÌÂÓÂ˜ ÛÙÔÓ ¶›Ó·Î· ‰fiÛÂÈ˜ ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó ÙË Ê·ÚÌ·ÎÂ˘ÙÈÎ‹ Ô˘Û›· Ô˘ ·ÂÏÂ˘ıÂÚÒÓÂÙ·È ·fi ÙË ‚·Ï‚›‰· ÙË˜ ‰ÔÛÈÌÂÙÚÈÎ‹˜ Û˘ÛÎÂ˘‹˜ (pMDI) ‹ Ô˘ ‚Ú›ÛÎÂÙ·È ‰È·ı¤ÛÈÌË ÌÂÙ¿ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙË˜ Û˘ÛÎÂ˘‹˜ ÍËÚ¿˜ ÛÎfiÓË˜ (DPI). √È ‰fiÛÂÈ˜ ·˘Ù¤˜ ‰ÂÓ Â›Ó·È ÔÈ ‰fiÛÂÈ˜ Ô˘ Êı¿ÓÔ˘Ó ÛÙÔÓ ·ÛıÂÓ‹. °›ÓÂÙ·È ·Ó·ÊÔÚ¿ (·ÏÊ·‚ËÙÈÎ¿) ÌfiÓÔ ÛÙ· ÂÈÛÓÂfiÌÂÓ· ∫™ Ô˘ Î˘ÎÏÔÊÔÚÔ‡Ó ÛÙËÓ ∂ÏÏ¿‰·. ** √È ·Ó·ÁÚ·ÊfiÌÂÓÂ˜ ÛÙÔÓ ¶›Ó·Î· ‰fiÛÂÈ˜ Â›Ó·È ÛÂ Ìg ÏËÓ ÂÎÂ›ÓˆÓ ÙÔ˘ ÂÓ·ÈˆÚ‹Ì·ÙÔ˜ ‚Ô˘‰ÂÛÔÓ›‰Ë˜ Ô˘ ·Ó·ÁÚ¿ÊÔÓÙ·È ÛÂ mg. *** ¢ÂÓ ·Ó·Ê¤ÚÂÙ·È Û˘ÓÈÛÙÒÌÂÓË ‰fiÛË ÛÂ ·È‰È¿ <12 ÂÙÒÓ (10).

ÚÔÛ¯ÔÏÈÎ‹ ËÏÈÎ›·. ∆· ÂÂÈÛfi‰È· ·˘Ù¿ Ê·›ÓÂÙ·È fiÙÈ ··ÓÙÔ‡Ó, ÙÔ˘Ï¿¯ÈÛÙÔÓ ÂÓ Ì¤ÚÂÈ, ÛÂ ‰È·ÏÂ›Ô˘Û· ·ÁˆÁ‹ ÌÂ ˘„ËÏ¤˜ ‰fiÛÂÈ˜ ÂÈÛÓÂfiÌÂÓˆÓ ∫™. øÛÙfiÛÔ, Ë ¯ÚfiÓÈ· ‹ ‰È·ÏÂ›Ô˘Û· ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë˜ ·ÁˆÁ‹ ÌÂ ¯·ÌËÏ‹ ‹ Ì¤ÙÚÈ· ‰fiÛË, ‰ÂÓ Ê·›ÓÂÙ·È Ó· ÚÔÛÙ·ÙÂ‡ÂÈ ·ÔÙÂÏÂÛÌ·ÙÈÎ¿ ·fi ÙÈ˜ ˘ÔÙÚÔ¤˜ (26,37).

∞ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎ¿ ∆· ·ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎ¿ ¤¯Ô˘Ó ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë Î·ıÒ˜ Î·È ÌÈÎÚ‹ ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ‹ ‰Ú¿ÛË ÛÙÔ ¿ÛıÌ·. ∆· Ê¿ÚÌ·Î· ·˘Ù¿ ‚ÂÏÙÈÒÓÔ˘Ó Ù· Û˘ÌÙÒÌ·Ù·, ÂÈÙ˘Á¯¿ÓÔ˘Ó Ì¤ÙÚÈ· ·‡ÍËÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÂÏ·ÙÙÒÓÔ˘Ó ÙÔ˘˜ ·ÚÔÍ˘ÛÌÔ‡˜ ÙË˜ ÓfiÛÔ˘. ∏ ‰Ú¿ÛË ÙÔ˘˜ ÛÙÔ Â›ÌÔÓÔ ¿ÛıÌ· ˘ÔÏÂ›ÂÙ·È ÂÎÂ›ÓË˜ ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ∫™ (38). ™Â ·È‰È¿ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ Û˘ÓÈÛÙÒÓÙ·È Î˘Ú›ˆ˜ ˆ˜ ÚfiÛıÂÙË ıÂÚ·Â›· (add-on therapy) ÛÙ· ÂÈÛÓÂfiÌÂÓ· ∫™ ÛÙÔ Ì¤ÙÚÈÔ (Â›ÌÔÓÔ), ·ÏÏ¿ Î·È ˆ˜ ÂÓ·ÏÏ·ÎÙÈÎ‹ ÌÔÓÔıÂÚ·Â›· ÛÙÔ ‹ÈÔ (Â›ÌÔÓÔ ‹ ˘ÔÙÚÔÈ¿˙ÔÓ) ¿ÛıÌ· (8,10,33,36). ªÔÚÂ› ÂÔÌ¤Óˆ˜, Ó· Û˘ÓÂÈÛÊ¤ÚÔ˘Ó ÛÙË ‰È·Ù‹ÚËÛË ÙË˜ ‰fiÛË˜ ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ∫™ ÛÂ ¯·ÌËÏ¿ Â›Â‰·. ™ËÌÂÈÒÓÂÙ·È fiÙÈ ÔÈ Û˘ÛÙ¿ÛÂÈ˜ ÙˆÓ Ï¤ÔÓ ‰È·‰Â‰ÔÌ¤ÓˆÓ ÔÌÔÊˆÓÈÒÓ ÁÈ· ÙË ıÂÚ·Â›· ÂÎÏÔÁ‹˜ ÙÔ˘ Â›ÌÔÓÔ˘ ¿ÛıÌ·ÙÔ˜ Ô˘ ‰ÂÓ ÂÏ¤Á¯ÂÙ·È ÌÂ ¯·ÌËÏ‹ ‰fiÛË ÂÈÛÓÂfiÌÂÓˆÓ ∫™ ·È‰ÈÒÓ ËÏÈÎ›·˜ <5 ÂÙÒÓ ‰ÂÓ Û˘Ì›ÙÔ˘Ó (8,10,33). ŒÙÛÈ: (·) Û‡ÌÊˆÓ· ÌÂ ÙË ¢ÈÂıÓ‹ √ÌÔÊˆÓ›· (GINA) ıÂÚ·Â›· ÂÎÏÔÁ‹˜ Â›Ó·È Ë ·‡ÍËÛË ÙÔ˘ ÂÈÛÓÂfiÌÂÓÔ˘ ∫™ ÛÙÔ Â›Â‰Ô ÙË˜ Ì¤ÙÚÈ·˜ ‰fiÛË˜ (¶›Ó·Î·˜ 1) (10), (‚) Û‡ÌÊˆÓ· ÌÂ ÙËÓ ∞ÌÂÚÈÎ·ÓÈÎ‹ √ÌÔÊˆÓ›· (NAEPP/EPR) Ë ıÂÚ·Â›· ÂÎÏÔÁ‹˜ Û˘Ó›ÛÙ·Ù·È ÛÙË ¯ÔÚ‹ÁËÛË Û˘Ó‰˘·ÛÌÔ‡ ¶·È‰È·ÙÚÈÎ‹ 2006;69:425-431

¯·ÌËÏ‹˜ ‰fiÛË˜ ÂÈÛÓÂfiÌÂÓÔ˘ ∫™ Î·È ‚2-·ÁˆÓÈÛÙ‹ Ì·ÎÚ¿˜ ‰Ú¿ÛË˜ (8), ÂÓÒ (Á) Ë µÚÂÙ·ÓÈÎ‹ √ÌÔÊˆÓ›· (BTS/SIGN) Û˘ÓÈÛÙ¿ ÙÔÓ Û˘Ó‰˘·ÛÌfi ¯·ÌËÏ‹˜ ‰fiÛË˜ ÂÈÛÓÂfiÌÂÓÔ˘ ∫™ Î·È ·ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (33). ™Â ÚfiÛÊ·ÙÂ˜ ÌÂÏ¤ÙÂ˜ ¤¯ÂÈ ‰ÈÂÚÂ˘ÓËıÂ› Ô ÚfiÏÔ˜ ÙˆÓ ·ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎÒÓ Î·È ÂÈ‰ÈÎfiÙÂÚ· ÙË˜ ÌÔÓÙÂÏÔ˘Î¿ÛÙË˜, ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Â›ÌÔÓÔ˘ Î·È ÙÔ˘ ˘ÔÙÚÔÈ¿˙ÔÓÙÔ˜ Û˘ÚÈÁÌÔ‡ ÛÙ· Ó‹È·. Œ¯ÂÈ ‰ÂÈ¯ıÂ› fiÙÈ, fiˆ˜ Û˘Ì‚·›ÓÂÈ ÌÂ Ù· ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ Î·È ÙÔ˘˜ ÂÓËÏ›ÎÔ˘˜, ¤ÙÛÈ Î·È ÛÙ· Ó‹È· ÌÂ Â›ÌÔÓ· ·ÛıÌ·ÙÈÎ¿ Û˘ÌÙÒÌ·Ù· Ë ¯ÔÚ‹ÁËÛË ÌÔÓÙÂÏÔ˘Î¿ÛÙË˜ Û˘ÓÔ‰Â‡ÂÙ·È ·fi ‚ÂÏÙ›ˆÛË ÌÈ·˜ ÛÂÈÚ¿˜ ÎÏÈÓÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ÙÔ˘ ¿ÛıÌ·ÙÔ˜ (ËÌÂÚ‹ÛÈ· Î·È Ó˘ÎÙÂÚÈÓ¿ Û˘ÌÙÒÌ·Ù·, ·ÚÈıÌfi˜ ·Û˘ÌÙˆÌ·ÙÈÎÒÓ ËÌÂÚÒÓ, ¯ÔÚ‹ÁËÛË ·Ó·ÎÔ˘ÊÈÛÙÈÎ‹˜ ıÂÚ·Â›·˜ ÌÂ ‚2-·ÁˆÓÈÛÙ¤˜ ‹ per os ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹). ∏ ‚ÂÏÙ›ˆÛË ·˘Ù‹ Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È ·ÓÂÍ¿ÚÙËÙË ·fi ÙË Û˘Ó‡·ÚÍË ·ÙÔ›·˜ ‹ ÙË Û˘Á¯ÔÚ‹ÁËÛË ÂÈÛÓÂfiÌÂÓÔ˘ ∫™ (39,40). ∂ÈÏ¤ÔÓ, ¤¯ÂÈ ‰ÂÈ¯ıÂ› Î·È ÛÙËÓ ËÏÈÎÈ·Î‹ ·˘Ù‹ ÔÌ¿‰· ‚ÂÏÙ›ˆÛË ÙfiÛÔ ÙË˜ ·Ó·ÓÂ˘ÛÙÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜, fiÛÔ Î·È ‰ÂÈÎÙÒÓ ÊÏÂÁÌÔÓ‹˜ (ÂÌÓÂfiÌÂÓÔ˘ NO, ËˆÛÈÓÔÊ›ÏˆÓ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜) ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ÌÔÓÙÂÏÔ˘Î¿ÛÙË˜ (41,42). ∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙË˜ ÌÔÓÙÂÏÔ˘Î¿ÛÙË˜ ˆ˜ ÌÔÓÔıÂÚ·Â›·˜ ÛÂ ·È‰È¿ 2-5 ÂÙÒÓ ÌÂ ‰È·ÏÂ›ÔÓÙ· Û˘ÌÙÒÌ·Ù· ¿ÛıÌ·ÙÔ˜ ÂÏ¤Á¯ıËÎÂ ÛÂ ÌÂÁ¿ÏË ‰ÈÏ‹-Ù˘ÊÏ‹ Ù˘¯·ÈÔÔÈËÌ¤ÓË ÌÂÏ¤ÙË. µÚ¤ıËÎÂ fiÙÈ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ‰ˆ‰ÂÎ¿ÌËÓË˜ ·ÁˆÁ‹˜ Ë ÌÔÓÙÂÏÔ˘Î¿ÛÙË ÂÏ¿ÙÙˆÛÂ ÙÔ˘˜ ·ÚÔÍ˘ÛÌÔ‡˜ ÙË˜ ÓfiÛÔ˘ Î·Ù¿ 32%, Î·ı˘ÛÙ¤ÚËÛÂ ÙËÓ ÂÎ‰‹ÏˆÛË ÙÔ˘ ÚÒÙÔ˘ ·ÚÔÍ˘ÛÌÔ‡ Î·È ÌÂ›ˆÛÂ Ù· ¯ÔÚËÁÔ‡ÌÂÓ· ÂÈÛÓÂfiÌÂÓ· ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ¿ Î·È ∫™ ÛÂ Û¯¤ÛË ÌÂ ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (43). ∆¤ÏÔ˜, ÛÂ Úfi‰ÚÔÌË Ù˘¯·ÈÔÔÈËÌ¤ÓË ‰ÈÏ‹-

429

∞ÓÙÈÌÂÙÒÈÛË Û˘ÚÈÁÌÔ‡ ‚ÚÂÊÒÓ Î·È ÓË›ˆÓ

Ù˘ÊÏ‹ ÌÂÏ¤ÙË ‰ÈÂÚÂ˘Ó‹ıËÎÂ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙË˜ ¯ÔÚ‹ÁËÛË˜ ÌÔÓÙÂÏÔ˘Î¿ÛÙË˜ Â› Ù¤ÛÛÂÚÈ˜ Â‚‰ÔÌ¿‰Â˜ ÛÙËÓ ÚfiÏË„Ë ÙˆÓ ÌÂÙ·‚ÚÔÁ¯ÈÔÏÈÙÈ‰ÈÎÒÓ Û˘ÌÙˆÌ¿ÙˆÓ (44). µÚ¤ıËÎÂ fiÙÈ ‚Ú¤ÊË 3-36 ÌËÓÒÓ Ô˘ ¤Ï·‚·Ó ÙËÓ ·ÁˆÁ‹ ÂÓÙfi˜ Â‚‰ÔÌ¿‰Ô˜ (‰È¿ÌÂÛË ÙÈÌ‹: 3 ËÌ¤ÚÂ˜) ·fi ÙËÓ ¤Ó·ÚÍË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ‚ÚÔÁ¯ÈÔÏ›ÙÈ‰·˜ Î·È ·Ú·ÎÔÏÔ˘ı‹ıËÎ·Ó Â› ¤Ó· Ì‹Ó·, ·ÚÔ˘Û›·Û·Ó ÂÚÈÛÛfiÙÂÚÂ˜ ·Û˘ÌÙˆÌ·ÙÈÎ¤˜ ËÌ¤ÚÂ˜ ¤Ó·ÓÙÈ ÙË˜ ÔÌ¿‰·˜ ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘, ÂÓÒ Ë ÛËÌ·ÓÙÈÎfiÙÂÚË ‰Ú¿ÛË ÙË˜ ÌÔÓÙÂÏÔ˘Î¿ÛÙË˜ ÂÎ‰ËÏÒıËÎÂ ÛÙËÓ ÚfiÏË„Ë ÙÔ˘ ÚˆÈÓÔ‡ ‚‹¯·. ∆· Î·Ù’ ·Ú¯‹Ó ÂÓı·ÚÚ˘ÓÙÈÎ¿ ·˘Ù¿ Â˘Ú‹Ì·Ù· ¯ÚÂÈ¿˙ÂÙ·È Ó· ÂÈ‚Â‚·ÈˆıÔ‡Ó ÌÂ ÚfiÛıÂÙÂ˜ ÎÏÈÓÈÎ¤˜ ÌÂÏ¤ÙÂ˜. ∆· Ì¤¯ÚÈ Û‹ÌÂÚ· ‰Â‰ÔÌ¤Ó· ‰Â›¯ÓÔ˘Ó fiÙÈ ÔÈ ·ÓÂÈı‡ÌËÙÂ˜ ÂÓ¤ÚÁÂÈÂ˜ ÙË˜ ÌÔÓÙÂÏÔ˘Î¿ÛÙË˜ ‰ÂÓ ‰È·Ê¤ÚÔ˘Ó ·fi ÂÎÂ›ÓÂ˜ ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ ÛÙ· ·È‰È¿ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜, fiˆ˜ ÂÍ¿ÏÏÔ˘ Û˘Ì‚·›ÓÂÈ Î·È ÌÂ Ù· ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ (39,43).

ÃÚˆÌfiÓÂ˜ Î·È Í·Óı›ÓÂ˜ (ıÂÔÊ˘ÏÏ›ÓÂ˜) √ ÚfiÏÔ˜ ÙˆÓ ¯ÚˆÌÔÓÒÓ (¯ÚˆÌÔÁÏ˘ÎÈÎfi Ó¿ÙÚÈÔ, ÓÂ‰Ô¯ÚˆÌ›ÏË) ÛÙË ıÂÚ·Â›· ÙÔ˘ ·È‰ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ ¤¯ÂÈ ÛËÌ·ÓÙÈÎ¿ ˘Ô‚·ıÌÈÛıÂ› Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·. ∞Ó Î·È ÛÂ ‰È¿ÊÔÚÂ˜ ÌÂÏ¤ÙÂ˜ ¤¯ÂÈ ‰ÂÈ¯ıÂ› fiÙÈ Ù· Ê¿ÚÌ·Î· ·˘Ù¿ Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚ· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ ÛÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Î·È ·ÔÙÚ¤Ô˘Ó ÙÔ˘˜ ·ÛıÌ·ÙÈÎÔ‡˜ ·ÚÔÍ˘ÛÌÔ‡˜, ÙÈ˜ ÂÈÛÎ¤„ÂÈ˜ ÛÂ ∆∂¶ Î·È ÙÈ˜ ÂÈÛ·ÁˆÁ¤˜ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô, ÚfiÛÊ·Ù· ‰Â‰ÔÌ¤Ó· ‰ÂÓ ÂÈ‚Â‚·ÈÒÓÔ˘Ó ÙË ¯ÚËÛÈÌfiÙËÙ¿ ÙÔ˘˜. ∏ ÌÂÁ·Ï‡ÙÂÚË Ù˘¯·ÈÔÔÈËÌ¤ÓË ÌÂÏ¤ÙË ÌÂ ÔÌ¿‰· ÂÏ¤Á¯Ô˘ ·È‰ÈÒÓ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ ÌÂ Ì¤ÙÚÈÔ ¿ÛıÌ· (218 ·ÛıÂÓÂ›˜) ‰ÂÓ ·Ó¤‰ÂÈÍÂ ‰È·ÊÔÚ¤˜ ÌÂÙ·Í‡ ¯ÚˆÌÔÁÏ˘ÎÈÎÔ‡ Ó·ÙÚ›Ô˘ Î·È ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (45), ÂÓÒ ÛÂ ÌÂÙ·-·Ó¿Ï˘ÛË 24 Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ‰ÈÏÒÓ Ù˘ÊÏÒÓ ÌÂÏÂÙÒÓ ÌÂ ÔÌ¿‰· ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ (ÂÚÈÛÛfiÙÂÚ· ·fi 1.000 ·È‰È¿ Û˘ÓÔÏÈÎ¿, ·fi Ù· ÔÔ›· Ù· ÌÈÛ¿ ÂÚ›Ô˘ ‹Ù·Ó Ó‹È·) ·ÌÊÈÛ‚ËÙÂ›Ù·È Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ ¯ÚˆÌÔÁÏ˘ÎÈÎÔ‡ ˆ˜ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ·ÓÙÈ·ÛıÌ·ÙÈÎ‹˜ ·ÁˆÁ‹˜ (46). ¶ÚfiÛÊ·ÙË ÌÂÁ¿ÏË Ì·ÎÚÔ¯ÚfiÓÈ· Ù˘¯·ÈÔÔÈËÌ¤ÓË ÌÂÏ¤ÙË ·ÛıÌ·ÙÈÎÒÓ ·È‰ÈÒÓ 5-12 ÂÙÒÓ ·fi ÙÈ˜ ∏¶∞ (ÌÂÏ¤ÙË CAMP) Û˘Ó¤ÎÚÈÓÂ ÙË Ì·ÎÚÔ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛË ‚Ô˘‰ÂÛÔÓ›‰Ë˜ Î·È ÓÂ‰Ô¯ÚˆÌ›ÏË˜ ÌÂ ÂÎÂ›ÓË ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. µÚ¤ıËÎÂ fiÙÈ Ë ÓÂ‰Ô¯ÚˆÌ›ÏË ÂÏ·ÙÙÒÓÂÈ ÌÂÓ ÙËÓ ·Ó¿ÁÎË ÂÂ›ÁÔ˘Û·˜ ıÂÚ·Â›-

·˜ ÁÈ· ¿ÛıÌ· Î·È ÙË ¯Ú‹ÛË per os ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰Ô‡˜, ·ÏÏ¿ ‰ÂÓ ÂËÚÂ¿˙ÂÈ Î·Ó¤Ó·Ó ¿ÏÏÔ ‰Â›ÎÙË ‚·Ú‡ÙËÙ·˜ (Û˘ÌÙÒÌ·Ù·, ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›·, ‚ÚÔÁ¯ÈÎ‹ ˘ÂÚ··ÓÙËÙÈÎfiÙËÙ·) (28). √È ¯ÚˆÌfiÓÂ˜ Â›Ó·È ÂÍ·ÈÚÂÙÈÎ¿ ·ÛÊ·Ï‹ Ê¿ÚÌ·Î· Î·È ÂÍ·ÎÔÏÔ˘ıÔ‡Ó Ó· ·ÔÙÂÏÔ‡Ó ÂÓ·ÏÏ·ÎÙÈÎ‹ Ì·ÎÚÔ¯ÚfiÓÈ· ·ÁˆÁ‹ ÛÙÔ ‹ÈÔ Â›ÌÔÓÔ ·È‰ÈÎfi ¿ÛıÌ·. ŸÌˆ˜, Ù· ·ÔÙÂÏ¤ÛÌ·Ù· ÙˆÓ ÌÂÏÂÙÒÓ Ô˘ ÚÔ·Ó·Ê¤ÚıËÎ·Ó, ÛÂ Û˘Ó‰˘·ÛÌfi ÌÂ ÙËÓ ·Ô‰Â‰ÂÈÁÌ¤ÓË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È ·ÛÊ¿ÏÂÈ· ¿ÏÏˆÓ Ê·ÚÌ¿ÎˆÓ (¯·ÌËÏ‹ ‰fiÛË ÂÈÛÓÂfiÌÂÓˆÓ ∫™, ·ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎ¿, Û˘Ó‰˘·ÛÌÔ›), Ô‰‹ÁËÛ·Ó ÛÙËÓ ÂÁÎ·Ù¿ÏÂÈ„Ë ·fi ÙÈ˜ ‰È¿ÊÔÚÂ˜ ÔÌÔÊˆÓ›Â˜ ÁÈ· ÙÔ ¿ÛıÌ·, ÙË˜ ·Ï·ÈfiÙÂÚË˜ Û‡ÛÙ·ÛË˜ ÁÈ· Î·Ù’ ·Ú¯‹Ó ‰ÔÎÈÌ·Û›· ¯ÚˆÌfiÓË˜ ÛÙÔ ·È‰ÈÎfi ‹ÈÔ Â›ÌÔÓÔ ¿ÛıÌ· (8,10,33). √È Í·Óı›ÓÂ˜ (ıÂÔÊ˘ÏÏ›ÓÂ˜) Â›Ó·È ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ¤˜ Ô˘Û›Â˜ ÌÂ ·ÓÔÛÔÙÚÔÔÔÈËÙÈÎ‹ ‰Ú¿ÛË (47), Î·È Ù· ÛÎÂ˘¿ÛÌ·Ù· ‚Ú·‰Â›·˜ ·Ô‰¤ÛÌÂ˘ÛË˜ ·ÔÙÂÏÔ‡Ó ÂÓ·ÏÏ·ÎÙÈÎ‹ ÚfiÛıÂÙË ÛÙ· ÂÈÛÓÂfiÌÂÓ· ∫™ ıÂÚ·Â›· ÁÈ· ÙÔ Ì¤ÙÚÈÔ (Â›ÌÔÓÔ) ¿ÛıÌ· ÙfiÛÔ ÙˆÓ ÌÂÁ·Ï‡ÙÂÚˆÓ, fiÛÔ Î·È ÙˆÓ ·È‰ÈÒÓ ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜ (8,10). ∞Ó Î·È Ë ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ¯ÔÚ‹ÁËÛË Î·È ÙÔ ¯·ÌËÏfi ÎfiÛÙÔ˜ ÙÔ˘˜ ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎ¿ ÚÔÙÂÚ‹Ì·Ù·, ÔÈ Û˘¯Ó¤˜ ·ÓÂÈı‡ÌËÙÂ˜ ÂÓ¤ÚÁÂÈÂ˜ Î·È Ù· ÚÔ‚Ï‹Ì·Ù· ·Ú·ÎÔÏÔ‡ıËÛË˜ ÙˆÓ ıÂÚ·Â˘ÙÈÎÒÓ ÂÈ¤‰ˆÓ ÛÙÔÓ ÔÚfi ÙˆÓ ÌÈÎÚÒÓ ·ÛıÂÓÒÓ Î·ıÈÛÙÔ‡Ó Û‹ÌÂÚ· ÙË ¯Ú‹ÛË ÙˆÓ ıÂÔÊ˘ÏÏÈÓÔ‡¯ˆÓ ÛÎÂ˘·ÛÌ¿ÙˆÓ ÂÈÏÔÁ‹ ¯·ÌËÏ‹˜ ÚÔÙÂÚ·ÈfiÙËÙ·˜ ÛÙÈ˜ ÂÚÈÛÛfiÙÂÚÂ˜ ‰˘ÙÈÎ¤˜ ¯ÒÚÂ˜. ¶ÚfiÛÊ·ÙÂ˜ ·Ó·ÊÔÚ¤˜, Ô˘ ·Ô‰ÂÈÎÓ‡Ô˘Ó ÙË Û˘Ó¤ÚÁÂÈ· ‰Ú¿ÛË˜ ÌÂÙ·Í‡ ÂÈÛÓÂÔÌ¤ÓˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰ÒÓ Î·È ¯·ÌËÏ‹˜ ‰fiÛË˜ ıÂÔÊ˘ÏÏ›ÓË˜ ÛÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ÁÔÓÈ‰›ˆÓ Ô˘ Ú˘ıÌ›˙Ô˘Ó ÙÔ˘˜ ÌË¯·ÓÈÛÌÔ‡˜ ÊÏÂÁÌÔÓ‹˜ ÛÙÔ ¿ÛıÌ·, ›Ûˆ˜ Ê¤ÚÔ˘Ó ÙËÓ Î·ÙËÁÔÚ›· ·˘Ù‹ Ê·ÚÌ¿ÎˆÓ Î·È ¿ÏÈ ÛÙÔ ÚÔÛÎ‹ÓÈÔ ÙÔ˘ ÂÓ‰È·Ê¤ÚÔÓÙÔ˜ (48).

™˘Ì¤Ú·ÛÌ· ∆· ÂÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ ÌÂ ÙËÓ ÈÛ¯˘Ú‹ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ‰Ú¿ÛË ÙÔ˘˜ Î·È ÙËÓ ¤ÏÏÂÈ„Ë ·ÓÂÈı‡ÌËÙˆÓ ÂÓÂÚÁÂÈÒÓ ÛÂ ¯·ÌËÏ¤˜ ‰fiÛÂÈ˜, ÌfiÓ· ‹ Û˘ÓÂÈÎÔ˘ÚÔ‡ÌÂÓ· ·fi Ù· ·ÓÙÈÏÂ˘ÎÔÙÚÈÂÓÈÎ¿, Ô˘ ¤¯Ô˘Ó ÙÔ ÏÂÔÓ¤ÎÙËÌ· ÙË˜ Â˘ÎÔÏ›·˜ Ù‹˜ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ¯ÔÚ‹ÁËÛ‹˜ ÙÔ˘˜, ·ÔÙÂÏÔ‡Ó ÙÈ˜ Û‡Á¯ÚÔÓÂ˜ ÂÈÏÔÁ¤˜ ÁÈ· ÙËÓ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë ·ÁˆÁ‹ ÙÔ˘ ˘ÔÙÚÔÈ¿˙ÔÓÙÔ˜ Û˘ÚÈÁÌÔ‡ ÛÙ· ¤ÓÙÂ ÚÒÙ· ¯ÚfiÓÈ· ÙË˜ ˙ˆ‹˜. √ ÚfiÏÔ˜ ÙˆÓ ¯ÚˆÌÔÓÒÓ ¤¯ÂÈ ˘Ô‚·ıÌÈÛıÂ› Ù· ¶·È‰È·ÙÚÈÎ‹ 2006;69:425-431

430

ª. B. ∞ÓıÚ·ÎﬁÔ˘ÏÔ˜ Î·È Û˘Ó.

ÙÂÏÂ˘Ù·›· ¯ÚﬁÓÈ·, ·Ó Î·È Ù· Ê¿ÚÌ·Î· ·˘Ù¿ ·Ú·Ì¤ÓÔ˘Ó ÂÓ·ÏÏ·ÎÙÈÎ‹ ÂÈÏÔÁ‹ Ì·ÎÚÔ¯ÚﬁÓÈ·˜ ÌÔÓÔıÂÚ·Â›·˜ ÛÙÔ ‹ÈÔ Â›ÌÔÓÔ ¿ÛıÌ·.

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∞ÓÙÈÌÂÙÒÈÛË Û˘ÚÈÁÌÔ‡ ‚ÚÂÊÒÓ Î·È ÓË›ˆÓ

30. Anhoj J, Bisgaard AM, Bisgaard H. Systemic activity of inhaled steroids in 1- to 3-year-old children with asthma. Pediatrics 2002;109:e40. 31. Sharek PJ, Bergman DA. Beclomethasone for asthma in children: effects on linear growth. Cochrane Database Syst Rev 2000;(2):CD001282. 32. Sharek PJ, Bergman DA. The effect of inhaled steroids on the linear growth of children with asthma: a metaanalysis. Pediatrics 2000;106:e8. 33. BTS/SIGN Guidelines for the management of asthma in adults and children. Thorax 1993;48 (Suppl):S1S24. Updated 2005. 34. Allen DB. Inhaled corticosteroid therapy for asthma in preschool children: growth issues. Pediatrics 2002;109 (2 Suppl):373-380. 35. Bahna SL. Is it time to reduce our phobia of inhaled corticosteroids? Pediatrics 2004;113:1813-1814. 36. ∫˘Ú‚·Û›ÏË˜ ºµ, ∆Û·Ó¿Î·˜ π¡. ∞ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ·È‰ÈÎÔ‡ ‚ÚÔÁ¯ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜. ¶Ô‡ Á¤ÚÓÂÈ Ë Ï¿ÛÙÈÁÁ·; ¶ÓÂ‡ÌˆÓ 2004;17:251-257. 37. McKean M, Ducharme F. Inhaled steroids for episodic viral wheeze of childhood. Cochrane Database Syst Rev 2000;(2):CD001107. 38. Ducharme FM, Di Salvio F. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev 2004;(1): CD002314. 39. Knorr B, Franchi LM, Bisgaard H, Vermeulen JH, LeSouef P, Santanello N, et al. Montelucast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 2001;108:e48. 40. Meyer KA, Arduino JM, Santanello NC, Knorr BA, Bisgaard H. Response to montelukast among subgroups of children aged 2 to 14 years with asthma. J Allergy Clin Immunol 2003;111:757-762.

41. Bisgaard H, Nielsen KG. Bronchoprotection with leukotriene receptor antagonist in asthmatic preschool children. Am J Respir Crit Care Med 2000; 162:187-190. 42. Straub DA, Moeller A, Minocchieri S, Hamacher J, Sennhauser FH, Hall GL, et al. The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma. Eur Respir J 2005;25:289-294. 43. Bisgaard H, Zielen S, Garcia-Garcia ML, Johnston SL, Gilles L, Menten J, et al. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma Am J Respir Crit Care Med 2005;171: 315-322. 44. Bisgaard H for the Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am Respir J Crit Care Med 2003;167: 379-383. 45. Tasche MJ, van der Wouden JC, Uijen JH, Ponsioen BP, Bernsen RM, van Suijlekom-Smit LW, et al. Randomised placebo-controlled trial of inhaled sodium cromoglycate in 1-4-year-old children with moderate asthma. Lancet 1997;350:1060-1064. 46. Tasche MJ, Uijen JH, Bernsen RM, de Jongste JC, van der Wouden JC. Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review. Thorax 2000;55: 913-920. 47. Kidney J, Dominguez M, Taylor PM, Rose M, Chung KF, Barnes PJ. Immunomodulation by theophylline in asthma. Demonstration by withdrawal of therapy. Am J Respir Crit Care Med 1995;151:1907-1914. 48. Barnes PJ. Theophylline: New perspectives for an old drug. Am J Respir Crit Care Med 2003;69:813-818.

¶·È‰È·ÙÚÈÎ‹ 2006;69:425-431

432

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ORIGINAL ARTICLE

H Û˘Ì‚ÔÏ‹ ÙË˜ ÚÒÈÌË˜ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ·˘ÙfiÓÔÌÔ˘ ÓÂ˘ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Î·È ·Ú·ÌÔÓ‹ ˘„ËÏ‹˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜ Î·Ù¿ ÙË Ó‡ÎÙ· ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ ÛÂ ÂÊ‹‚Ô˘˜ ÌÂ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 1 µ’ ÃˆÚ¤ÌÂÈÔ Œ·ıÏÔ ÛÙÔ 44Ô ¶·ÓÂÏÏ‹ÓÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ, ƒfi‰Ô˜, 9-11 πÔ˘Ó›Ô˘ 2006 1 ¢È·‚ËÙÔÏÔÁÈÎfi ∆Ì‹Ì·, µ’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó· 2 ∫·Ú‰ÈÔÏÔÁÈÎ‹ ∫ÏÈÓÈÎ‹, 7Ô ¡ÔÛÔÎÔÌÂ›Ô π.∫.∞., ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ∫˘ÚÈ·Î‹ K·Ú·‚·Ó¿ÎË ∂ÏÏËÓÈÎÔ‡ ™ÙÚ·ÙÔ‡ 22∞, ∆.∫. 152 37, ºÈÏÔı¤Ë, ∞ı‹Ó· ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 23-10-2006 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 24-10-2006

∫. K·Ú·‚·Ó¿ÎË1, °. ∫·˙È¿ÓË˜2, Ã. ∫·Ú·ÁÈ¿ÓÓË1, ∞. ™Î·Ú‰Ô‡ÙÛÔ˘1, ∫. ∫·ÎÏ¤·˜1, ∞. ∫ˆÓÛÙ·ÓÙﬁÔ˘ÏÔ˜1

¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: ™ÎÔfi˜ ÙË˜ ·ÚÔ‡Û·˜ ÌÂÏ¤ÙË˜ ‹Ù·Ó Ë ÂÎÙ›ÌËÛË ÙË˜ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÌÂÙ·‚ÔÏÒÓ ÙË˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜ (∞¶) Î·Ù¿ ÙË Ó‡ÎÙ· Î·È ÙË˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ·˘ÙfiÓÔÌÔ˘ ÓÂ˘ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (∞¡™) ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ ÛÂ ÂÊ‹‚Ô˘˜ ÌÂ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 1 (™¢1). ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ªÂÏÂÙ‹ıËÎ·Ó 22 ¤ÊË‚ÔÈ ËÏÈÎ›·˜ 16,7±4,1 ÂÙÒÓ ÌÂ ™¢ Ù‡Ô˘ 1. ŒÁÈÓÂ 24ˆÚË Î·Ù·ÁÚ·Ê‹ ÙË˜ ∞¶, ÂÓÒ Ë ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ∞¡™ ÌÂÏÂÙ‹ıËÎÂ ÌÂ 24ˆÚË Î·Ù·ÁÚ·Ê‹ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ Î·È ·Ó·Ï‡ıËÎÂ ÌÂ ÙË Ì¤ıÔ‰Ô power spectra. ∏ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›· ÂÎÙÈÌ‹ıËÎÂ ÌÂ 12ˆÚÂ˜ Û˘ÏÏÔÁ¤˜ Ô‡ÚˆÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ËÌ¤Ú·˜/Ó‡ÎÙ·˜. √È ¤ÊË‚ÔÈ ¯ˆÚ›ÛÙËÎ·Ó ÛÂ ‰‡Ô ÔÌ¿‰Â˜, ·Ó¿ÏÔÁ· ÌÂ ÙË ‰È¿ÌÂÛË ÙÈÌ‹ ÏÂ˘ÎˆÌ·Ù›ÓË˜ Ô‡ÚˆÓ 12ÒÚÔ˘ (1Ë ÔÌ¿‰·: ≥7,5 Ìg/min, 2Ë ÔÌ¿‰·: <7,5 Ìg/min). ∞ÔÙÂÏ¤ÛÌ·Ù·: ¢È·ÈÛÙÒıËÎÂ fiÙÈ Ë 1Ë ÔÌ¿‰· Â›¯Â ˘„ËÏfiÙÂÚÂ˜ ÙÈÌ¤˜ Ì¤ÛË˜ Û˘ÛÙÔÏÈÎ‹˜ (™¶) (109,3 vs 106,5 mmHg, p=0,028) Î·È Ì¤ÛË˜ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ (¢¶) Î·Ù¿ ÙË Ó‡ÎÙ· (77,8 vs 73,6 mmHg, p=0,035), ·ÓÙ›ÛÙÔÈ¯·, Î·ıÒ˜ Â›ÛË˜ Î·È ˘„ËÏfiÙÂÚÂ˜ ÙÈÌ¤˜ ÙË˜ ·Ú·Ì¤ÙÚÔ˘ pNN50 ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (32,9% vs 19,9%, p<0,009). ™ÙË Û˘Ó¤¯ÂÈ·, ÔÈ ·ÛıÂÓÂ›˜ ¯ˆÚ›ÛÙËÎ·Ó ·Ó¿ÏÔÁ· ÌÂ ÙËÓ ·Ô˘Û›· ÙÒÛË˜ (non-dippers) ‹ ÙËÓ ÙÒÛË (dippers) ÙË˜ ¢¶ Î·Ù¿ ÙË Ó‡ÎÙ·. ∏ oÌ¿‰· ÙˆÓ non-dippers ·ÚÔ˘Û›·˙Â Î·Ù¿ ÙË Ó‡ÎÙ· ˘„ËÏfiÙÂÚË ÙÈÌ‹ Ì¤ÛÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (RR) (916 vs 764 ms, p=0,001) Î·È ˘„ËÏfiÙÂÚË ·Ú¿ÌÂÙÚÔ SDNN-i (110,6 vs 88,1 ms, p=0,018) Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÂÎÂ›ÓË ÙˆÓ dippers, ÂÓÒ ‰ÂÓ ˘‹Ú¯Â ‰È·ÊÔÚ¿ ÛÙËÓ ·¤ÎÎÚÈÛË ÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· (∞§√). ∆Ô ËÏ›ÎÔ ÙË˜ ¢¶ Ó‡ÎÙ·˜/ËÌ¤Ú·˜ Û˘Û¯ÂÙÈ˙fiÙ·Ó ıÂÙÈÎ¿ ÌÂ ÙÔÓ Î·Ú‰È·Îfi Ú˘ıÌfi RR (r=0,49, p=0,001). ™˘ÌÂÚ¿ÛÌ·Ù·: ¢È·ÈÛÙÒÓÂÙ·È fiÙÈ ÛÂ ÂÊ‹‚Ô˘˜ ™¢1 ÔÈ ÚÒÈÌÂ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ∞¡™ Î·È ÙË˜ A¶ ÚÔËÁÔ‡ÓÙ·È ÙË˜ ÂÎ‰‹ÏˆÛË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ Î·È Â›Ó·È ‰˘Ó·Ùfi Ó· Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ·Ú¯fiÌÂÓË˜ ÓÂÊÚÔ¿ıÂÈ·˜. §¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ™·Î¯·ÚÒ‰Ë˜ ‰È·‚‹ÙË˜ Ù‡Ô˘ 1, ·ÚÙËÚÙÈ·Î‹ ˘¤ÚÙ·ÛË, ‰È·Ù·Ú·¯‹ ·˘ÙfiÓÔÌÔ˘ ÓÂ˘ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜.

The contribution of nocturnal blood pressure change and autonomic dysfunction in the pathogenesis of microalbuminuria in adolescents with type 1 diabetes mellitus 2nd Choremeio Prize at the 44th Panhellenic Paediatric Congress, Rhodes, 9-11 June, 2006

K. Karavanaki1, G. Kazianis2, C. Karagianni1, A. Skardoutsou1, C. Kakleas1, A. Constantopoulos1

1 Diabetic Clinic, 2nd Paediatric Department, University of Athens, “P. & A. Kyriakou” Children’s Hospital, Athens 2 Cardiology Clinic, 7th IKA Hospital, Athens

pressure (DBP) changes and autonomic function in the pathogenesis of microalbuminuria in adolescents with type 1 diabetes mellitus (DM1). Methods: Twenty-two normotensive, normoalbuminuric adolescents with DM1 were studied, aged 16.7±4.1 years. Twenty-four-hour ambulatory BP was recorded. Twenty-four-hour heart rate spectral analysis. Microalbuminuria was evaluated in 24-hour urine collections. The adolescents were divided into

Abstract Background: The aim of the present study was to evaluate the contribution of nocturnal blood

H ÂÚÁ·Û›· ·˘Ù‹ ‚Ú·‚Â‡ıËÎÂ ÌÂ ÙÔ Bã ÃˆÚ¤ÌÂÈÔ Œ·ıÏÔ ÛÙÔ 44Ô ¶·ÓÂÏÏ‹ÓÈÔ ¶·È‰È·ÙÚÈÎﬁ ™˘Ó¤‰ÚÈÔ, ƒﬁ‰Ô˜, 9-11 πÔ˘Ó›Ô˘ 2006 ¶·È‰È·ÙÚÈÎ‹ 2006;69:432-439

433

¢È·Ù·Ú·¯¤˜ ÙÔ˘ ∞¡™ Î·È ÙË˜ ™¶ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ ÛÂ ™¢1

monitoring, as an index of autonomic neuropathy, was also performed and was analyzed with power Results: In the first group, higher values of mean systolic blood pressure (SBP) (109.3 vs 106.5 mmHg, p=0.028) and mean DBP during night (77.8 vs 73.6 mmHg, p=0.035) and faster heart rate (pNN50: 32.9% vs 19.9%, p<0.009) were observed, in comparison with the second group. Furthermore the patients were divided into another two groups according to the absence of decrease (non-dippers) or the decrease (dippers) of DBP during night. In the non-dippers’ group, mean heart rate RR during night (916.0 vs 764.4 ms, p=0.001) and parameter SDNN-i were faster (110.6 vs 88.1 ms, p=0.018) in comparison with the dippers’ group, while no difference was observed in terms of nocturnal UAE. DBP ratio was positively related to HR (r=0.49, p=0.001). Conclusions: In conclusion, early impairments of ANS and DBP seem to precede the development of microalbuminuria and they possibly contribute to its pathogenesis.

Correspondence: Kyriaki Karavanaki 22A, Ellinikou Stratou St. 152 37, Filothei, Athens Date of submission: 23-10-2006 Date of approval: 24-10-2006

Key words: Type 1 diabetes mellitus, arterial hypertension, autonomic dysfunction.

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ ™¢1 ∞¡™ ¢∞¡ ¢¡ ∞¶ ™¶ ∞§√ HRV

™·Î¯·ÚÒ‰Ë˜ ‰È·‚‹ÙË˜ Ù‡Ô˘ 1 ∞˘ÙfiÓÔÌÔ ÓÂ˘ÚÈÎfi Û‡ÛÙËÌ· ¢È·‚ËÙÈÎ‹ ·˘ÙfiÓÔÌË ÓÂ˘ÚÔ¿ıÂÈ· ¢È·‚ËÙÈÎ‹ ÓÂÊÚÔ¿ıÂÈ· ∞ÚÙËÚÈ·Î‹ ›ÂÛË ™˘ÛÙÔÏÈÎ‹ ›ÂÛË ∞¤ÎÎÚÈÛË ÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· ªÂÙ·‚ÏËÙfiÙËÙ· Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (heart rate variability) PSA ∞Ó¿Ï˘ÛË Î·Ù¿ power spectra (power spectral analysis) HF ¶ÂÚÈÔ¯¤˜ ˘„ËÏ‹˜ Û˘¯ÓfiÙËÙ·˜ ÙË˜ HRV (high frequency) LF ¶ÂÚÈÔ¯¤˜ ¯·ÌËÏ‹˜ Û˘¯ÓfiÙËÙ·˜ ÙË˜ HRV (low frequency) pNN50 ¶ÔÛÔÛÙfi ÙˆÓ ‰È·ÊÔÚÒÓ ÌÂÙ·Í‡ ÙˆÓ Û˘ÓÂ¯fiÌÂÓˆÓ R-R ‰È·ÛÙËÌ¿ÙˆÓ >50 ms Î·Ù¿ ÙË Ó‡ÎÙ· SDNN-i ª¤ÛË ÙÈÌ‹ ÙˆÓ ÛÙ·ıÂÚÒÓ ·ÔÎÏ›ÛÂˆÓ fiÏˆÓ ÙˆÓ ÊÈÏÙÚ·ÚÈÛÌ¤ÓˆÓ ‰È·ÛÙËÌ¿ÙˆÓ RR ÁÈ· Î¿ıÂ ‰È¿ÛÙËÌ· 5 mm Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘

EÈÛ·ÁˆÁ‹ ∏ ·ıÔÁ¤ÓÂÈ· ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÓÂÊÚÔ¿ıÂÈ·˜ (¢¡) Û˘Û¯ÂÙ›˙ÂÙ·È ÌÂ ÙËÓ ÂÌÊ¿ÓÈÛË ˘¤ÚÙ·ÛË˜. ∫·Ù¿ ÙÔ ˘ÔÎÏÈÓÈÎfi ÛÙ¿‰ÈÔ ÙË˜ ¢¡ ÛÂ ·ÛıÂÓÂ›˜ ÌÂ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 1 (™¢1), Û˘Ó‹ıˆ˜ Ë ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›· ÚÔËÁÂ›Ù·È ÙË˜ ˘¤ÚÙ·ÛË˜ (1) ‹ Û·ÓÈfiÙÂÚ· ·Ó·Ù‡ÛÛÂÙ·È ·Ú¿ÏÏËÏ· (2,3). ∞ÓÙ›ıÂÙ·, ÛÂ ·ÛıÂÓÂ›˜ ÌÂ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 2 (™¢2), fiÙ·Ó ‰È·ÁÈÁÓÒÛÎÂÙ·È Ë ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·, Ë ˘¤ÚÙ·ÛË Â›Ó·È ‹‰Ë ÂÁÎ·ÙÂÛÙËÌ¤ÓË (4). ¶ÚfiÛÊ·ÙÂ˜ ÌÂÏ¤ÙÂ˜ ÌÂ 24ˆÚË Î·Ù·ÁÚ·Ê‹ ÙË˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜ (∞¶) ÛÂ ÂÓ‹ÏÈÎÂ˜ ÌÂ ™¢1 (5,6), ·Ó·Ê¤ÚÔ˘Ó ˘„ËÏfiÙÂÚÂ˜ ÙÈÌ¤˜ ∞¶ Î·Ù¿ ÙË Ó‡ÎÙ· ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘-

Ú›·, ÛÂ Û‡ÁÎÚÈÛË ÌÂ ÂÎÂ›ÓÔ˘˜ ¯ˆÚ›˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·. ∂›ÛË˜, ÔÈ Lurbe Î·È Û˘Ó (7) ·Ó·Ê¤ÚÔ˘Ó fiÙÈ Ë ·‡ÍËÛË ÙË˜ ™¶ ÛÂ ‰È·‚ËÙÈÎÔ‡˜ ÂÊ‹‚Ô˘˜ Î·Ù¿ ÙË Ó‡ÎÙ· ÚÔËÁÂ›Ù·È ÙË˜ ÂÌÊ¿ÓÈÛË˜ ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ Î·È fiÙÈ Â›Ó·È Èı·Ófi Ó· Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ·ıÔÁ¤ÓÂÈ¿ ÙË˜. √È ‰È·Î˘Ì¿ÓÛÂÈ˜ ÙË˜ ∞¶ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘ ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛÙÂ› ÌÂ ‰È·Ù·Ú·¯¤˜ ÙË˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ·˘ÙfiÓÔÌÔ˘ ÓÂ˘ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (∞¡™) (8). ™Â ÂÓ‹ÏÈÎÂ˜ ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓÂ›˜ ÌÂ ·Ú¯fiÌÂÓÔ ÛÙ¿‰ÈÔ ¢¡, Ë ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›· ¤¯ÂÈ Û˘Û¯ÂÙÈÛÙÂ› ÌÂ ÙËÓ ·ÚÔ˘Û›· ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ ∞¡™ (9). ™Â ‰È·‚ËÙÈÎ¿ ·È‰È¿, Ë ·ÚÔ˘Û›· ·˘ÍËÌ¤ÓˆÓ ÙÈÌÒÓ ∞§√ Û˘Û¯ÂÙÈ˙fiÙ·Ó ÌÂ ÙËÓ ·ÚÔ˘Û›· ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ Î·È ˘„ËÏÒÓ ÙÈÌÒÓ ∞¶ (10,11). ∆›ıÂÙ·È, Û˘ÓÂÒ˜, ÙÔ ÂÚÒÙËÌ· Â¿Ó Ë ‰È·‚ËÙÈÎ‹ ·˘ÙfiÓÔÌË ÓÂ˘ÚÔ¿ıÂÈ· (¢∞¡) Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÓÂÊÚÔ¿ıÂÈ·˜, Ì¤Ûˆ ‰È·Ù·Ú·¯ÒÓ ÛÙË ‰È·Î‡Ì·ÓÛË ÙË˜ ∞¶ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘. ª¤¯ÚÈ ÚfiÛÊ·Ù·, ÔÈ ÌÂÏ¤ÙÂ˜ Ô˘ ÂÚÂ˘ÓÔ‡Ó ÙË Û˘Û¯¤ÙÈÛË ·ıÔÏÔÁÈÎÒÓ ‰ÂÈÎÙÒÓ ¢∞¡ ÌÂ ÙË ÌÂÙ·‚ÔÏ‹ ÙË˜ ∞¶ Î·Ù¿ ÙË Ó‡ÎÙ· ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ‹ ¯ˆÚ›˜ ÚˆÙÂ˚ÓÔ˘Ú›·, ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÂÓ‹ÏÈÎÂ˜ (12,13). °È’ ·˘ÙÔ‡˜ ÙÔ˘˜ ÏfiÁÔ˘˜ Û¯Â‰È¿ÛÙËÎÂ Ë ·ÚÔ‡Û· ÌÂÏ¤ÙË, ÌÂ ÛÎÔfi Ó· ÌÂÏÂÙËıÂ› ÛÂ ÂÊ‹‚Ô˘˜ ÌÂ ™¢1 Ë Û˘Û¯¤ÙÈÛË ÙË˜ ÌÂÙ·‚ÔÏ‹˜ ÙË˜ ∞¢¶ Î·Ù¿ ÙË Ó‡ÎÙ· ÌÂ ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ∞¡™ Î·È ÙËÓ ·¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ Î·Ù¿ ÙË Ó‡ÎÙ·.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ∏ ·ÚÔ‡Û· ÌÂÏ¤ÙË Â›Ó·È Úfi‰ÚÔÌË ÚÔÔÙÈÎ‹˜ Ì·ÎÚÔ¯ÚfiÓÈ·˜ ÌÂÏ¤ÙË˜ ÙË˜ ¢∞¡ Î·È ¢¡, Ô˘ ‰ÈÂÓÂÚÁÂ›Ù·È ¶·È‰È·ÙÚÈÎ‹ 2006;69:432-439

434

∫. K·Ú·‚·Ó¿ÎË Î·È Û˘Ó.

ÛÂ ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ ÌÂ ‰È¿ÚÎÂÈ· ÓfiÛÔ˘ >5 ¯ÚfiÓÈ·, Ù· ÔÔ›· ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÛÙÔ ¢È·‚ËÙÔÏÔÁÈÎfi ∂ÍˆÙÂÚÈÎfi È·ÙÚÂ›Ô ÙË˜ ÎÏÈÓÈÎ‹˜ Ì·˜. ∞˘Ù‹ Ë ÌÂÏ¤ÙË ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· ÚÒÙ· ·ÔÙÂÏ¤ÛÌ·Ù· Ô˘ ÂÏ‹ÊıËÛ·Ó ÌÂÙ¿ ·fi ·Ú·ÎÔÏÔ‡ıËÛË 22 ·ÛıÂÓÒÓ. ªÂıÔ‰ÔÏÔÁ›· ∞. MÂÏ¤ÙË ÙË˜ 24ˆÚË˜ ‰È·Î‡Ì·ÓÛË˜ ÙË˜ ∞¶: ∆ÔÔıÂÙ‹ıËÎÂ Holter ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜ ÁÈ· 24 ÒÚÂ˜, Ô˘ Î·Ù¤ÁÚ·ÊÂ ÙÈÌ¤˜ ·Ó¿ 30 min ÙËÓ ËÌ¤Ú· Î·È ·Ó¿ 1 ÒÚ· ÙË Ó‡ÎÙ·. ÃÚËÛÈÌÔÔÈ‹ıËÎÂ Ë Û˘ÛÎÂ˘‹ Holter Medilog ABP. ªÂÏÂÙ‹ıËÎ·Ó ÔÈ ÂÍ‹˜ ·Ú¿ÌÂÙÚÔÈ ÙË˜ ∞¶: ·) Max Î·È Ì¤ÛË Û˘ÛÙÔÏÈÎ‹ ›ÂÛË 24ÒÚÔ˘ Î·È SD, ‚) ªax Î·È Ì¤ÛË ‰È·ÛÙÔÏÈÎ‹ ›ÂÛË 24ˆÚÔ˘ Î·È SD, Á) Ì¤ÛË Û˘ÛÙÔÏÈÎ‹ ›ÂÛË ËÌ¤Ú·˜ (12ÒÚÔ˘) Î·È SD, ‰) Ì¤ÛË ‰È·ÛÙÔÏÈÎ‹ ›ÂÛË ËÌ¤Ú·˜ (12ÒÚÔ˘) Î·È SD, Â) Ì¤ÛË Û˘ÛÙÔÏÈÎ‹ ›ÂÛË Ó‡ÎÙ·˜ (12ÒÚÔ˘) Î·È SD, ÛÙ) Ì¤ÛË ‰È·ÛÙÔÏÈÎ‹ ›ÂÛË Ó‡ÎÙ·˜ (12ÒÚÔ˘) Î·È SD, ˙) ËÏ›ÎÔ Û˘ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Ó‡ÎÙ·˜/ËÌ¤Ú·˜ Î·È Ë) ËÏ›ÎÔ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Ó‡ÎÙ·˜/ËÌ¤Ú·˜. º˘ÛÈÔÏÔÁÈÎ¤˜ ÙÈÌ¤˜ ÁÈ· ÙËÓ ·ÚÙËÚÈ·Î‹ ›ÂÛË ÂÏ‹ÊıËÛ·Ó ·fi ÚÔËÁÔ‡ÌÂÓÂ˜ ÌÂÏ¤ÙÂ˜ (14). µ. ªÂÏ¤ÙË ÙË˜ 24ˆÚË˜ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (Heart rate variability) (ˆ˜ ‰Â›ÎÙË˜ ·˘ÙfiÓÔÌË˜ ÓÂ˘ÚÔ¿ıÂÈ·˜) Î·È ·Ó¿Ï˘Û‹ ÙÔ˘ ÌÂ ÙË Ì¤ıÔ‰Ô power spectra. ∆ÔÔıÂÙ‹ıËÎÂ Holter Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘. ÃÚËÛÈÌÔÔÈ‹ıËÎÂ Ë Û˘ÛÎÂ˘‹ Holter Ù‡Ô˘ Medilog 4,500 P (Oxford). √È Ù·ÈÓ›Â˜ ·Ó·Ï‡ıËÎ·Ó ÌÂ ÙÔ ÚfiÁÚ·ÌÌ· Medilog Excel, version 5.0 (Oxford). º˘ÛÈÔÏÔÁÈÎ¤˜ ÙÈÌ¤˜ ÁÈ· ÙÈ˜ ·Ú·Ì¤ÙÚÔ˘˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ ÌÂ ÙË Ì¤ıÔ‰Ô power spectra ÂÏ‹ÊıËÛ·Ó ·fi ÚÔËÁÔ‡ÌÂÓÂ˜ ÌÂÏ¤ÙÂ˜ (8). ∏ ÌÂÏ¤ÙË ÙË˜ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ ÌÂ ÙË Ì¤ıÔ‰Ô PSA ÂÚÈÂÏ¿Ì‚·ÓÂ: i) ÙËÓ ·Ó¿Ï˘ÛË ÛÙÔÓ ¯ÚfiÓÔ (time domain analysis) Î·È ii) ÙËÓ ·Ó¿Ï˘ÛË Î·Ù¿ Û˘¯ÓfiÙËÙÂ˜ (frequency domain analysis) (15). ∏ ·Ó¿Ï˘ÛË ÛÙÔÓ ¯ÚfiÓÔ ·Ó·Ê¤ÚÂÙ·È ÛÙË ÌÂÏ¤ÙË ÙË˜ ÛÙ·ıÂÚ‹˜ ·fiÎÏÈÛË˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ ÛÙË ÌÔÓ¿‰· ÙÔ˘ ¯ÚfiÓÔ˘ (R-R intervals/time) (16). √È ·Ú¿ÌÂÙÚÔÈ Ô˘ ÌÂÏÂÙÒÓÙ·È Â›Ó·È ÔÈ ·ÎfiÏÔ˘ıÂ˜: ·) ª¤ÛÔ˜ RR (Ì¤ÛË ÙÈÌ‹ fiÏˆÓ ÙˆÓ ÊÈÏÙÚ·ÚÈÛÌ¤ÓˆÓ ‰È·ÛÙËÌ¿ÙˆÓ RR), ‚) SDNN [ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË (SD) ÙˆÓ ‰È·ÛÙËÌ¿ÙˆÓ R-R intervals Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘], Á) SDNNi (Ì¤ÛË ÙÈÌ‹ ÙˆÓ ÛÙ·ıÂÚÒÓ ·ÔÎÏ›ÛÂˆÓ fiÏˆÓ ÙˆÓ ÊÈÏÙÚ·ÚÈÛÌ¤ÓˆÓ ‰È·ÛÙËÌ¿ÙˆÓ RR ÁÈ· Î¿ıÂ ‰È¿ÛÙËÌ· 5 ÏÂÙÒÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘), ‰) SDAN-i (ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË ÙˆÓ SDNNi), Â) pNN50 (ÔÛÔÛÙfi ÙˆÓ ‰È·ÊÔÚÒÓ ÌÂÙ·Í‡ ÙˆÓ Û˘ÓÂ¯fiÌÂÓˆÓ R-R ‰È·ÛÙËÌ¿ÙˆÓ >50 ms Î·Ù¿ ÙË Ó‡ÎÙ·) Î·È ÛÙ) r-MSSD (ÙÂÙÚ·ÁˆÓÈÎ‹ Ú›˙· ÙÔ˘ Ì¤ÛÔ˘ fiÚÔ˘ ÙÔ˘ ·ıÚÔ›ÛÌ·ÙÔ˜ ÙˆÓ ÙÂÙÚ·ÁÒÓˆÓ ÙË˜ pNN50). ∆o SDAN-i ·ÔÙÂÏÂ› ÙËÓ Î·Ï‡ÙÂÚË ·Ú¿ÌÂÙÚÔ Ì¤ÙÚËÛË˜ ÙË˜ ÎÈÚÎ·‰›Ô˘ ÌÂÙ·‚ÔÏ‹˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (16), ÂÓÒ ÔÈ ·Ú¿ÌÂÙÚÔÈ pNN50 Î·È rMSSD ıÂˆÚÔ‡ÓÙ·È ¿ÚÈÛÙÔÈ ‰Â›ÎÙÂ˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ·Ú·Û˘Ì·ıËÙÈÎÔ‡ (16). °È· ÙËÓ ·Ó¿Ï˘ÛË ÙË˜ HRV Î·Ù¿ Û˘¯ÓfiÙËÙÂ˜ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Ë Ù·¯Â›· ·Ó¿Ï˘ÛË Î·Ù¿ Fourier (17). ™‡ÌÊˆÓ· ÌÂ ·˘Ù‹, ÔÈ ‰È·Î˘Ì¿ÓÛÂÈ˜ ÛÙÔ Â‡ÚÔ˜ ÙˆÓ ‰È·ÛÙËÌ¿ÙˆÓ R-R ÌÂÙ·ÙÚ¤ÔÓÙ·È ÛÂ Î˘Ì·ÙÔÌÔÚÊ¤˜ Û˘¯ÓÔÙ‹ÙˆÓ Î·È ÂÎÊÚ¿˙Ô˘Ó ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Û˘Ì·ıËÙÈÎÔ‡ Î·È ÙÔ˘ ·Ú·Û˘Ì·ıËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (17). ªÂÏÂÙÒÓÙ·È ‰‡Ô ÔÌ¿‰Â˜ Û˘¯ÓÔÙ‹ÙˆÓ: ·) Ë ÔÌ¿‰· ˘„ËÏÒÓ ¶·È‰È·ÙÚÈÎ‹ 2006;69:432-439

Û˘¯ÓÔÙ‹ÙˆÓ (HF: 0,15-0,50 Hz), Ô˘ ·ÔÙÂÏÔ‡Ó ‰Â›ÎÙÂ˜ ÙË˜ ·Ú·Û˘Ì·ıËÙÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜, ÂÍ·ÚÙÒÓÙ·È ·fi ÙËÓ ·Ó·ÓÔ‹ Î·È Â›Ó·È ˘„ËÏfiÙÂÚÂ˜ ÛÙËÓ ‡ÙÈ· ı¤ÛË (17) Î·È ‚) Ë ÔÌ¿‰· ¯·ÌËÏÒÓ Û˘¯ÓÔÙ‹ÙˆÓ (LF: 0,050,15 Hz), Ë ÔÔ›· ÛÙËÓ ‡ÙÈ· ı¤ÛË ÂÍ·ÚÙ¿Ù·È Î˘Ú›ˆ˜ ·fi ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ·Ú·Û˘Ì·ıËÙÈÎÔ‡, ÂÓÒ ÛÙËÓ fiÚıÈ· ı¤ÛË ÂËÚÂ¿˙ÂÙ·È ·fi ·ÏÏËÏÂ›‰Ú·ÛË Û˘Ì·ıËÙÈÎÔ‡ Î·È ·Ú·Û˘Ì·ıËÙÈÎÔ‡ (17). ∂ÈÏ¤ÔÓ, ˘ÔÏÔÁ›ÛÙËÎÂ ÙÔ ËÏ›ÎÔ HF/LF Ô˘ ·ÔÙÂÏÂ›, Â›ÛË˜, ·ÍÈfiÈÛÙÔ ‰Â›ÎÙË ÈÛÔÚÚÔ›·˜ ÌÂÙ·Í‡ ÙË˜ ÏÂÈÙÔ˘ÚÁ›·˜ Û˘Ì·ıËÙÈÎÔ‡-·Ú·Û˘Ì·ıËÙÈÎÔ‡ (17). ø˜ ÂÚ›Ô‰Ô˜ ‡ÓÔ˘ ÛÙËÓ ·ÚÔ‡Û· ÌÂÏ¤ÙË ÔÚ›ÛÙËÎÂ ÙÔ ‰È¿ÛÙËÌ· 10 ÌÌ-8 Ì, ÂÓÒ Ë Î·Ù·ÁÚ·Ê‹ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ Î·È ÙË˜ ∞¶ ¤ÁÈÓÂ ÌÂ Holter. °. ∫·Ú‰ÈÔÏÔÁÈÎ‹ ÂÎÙ›ÌËÛË: ·) ÀÂÚË¯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ Î·Ú‰È¿˜ (2D-Echo Doppler). ÃÚËÛÈÌÔÔÈ‹ıËÎÂ Ë Û˘ÛÎÂ˘‹ ATL 5000 HDI. ªÂÏÂÙ‹ıËÎ·Ó ÔÈ ÂÍ‹˜ ·Ú¿ÌÂÙÚÔÈ: i) ‰È·ÛÙ¿ÛÂÈ˜ Ô›ÛıÈÔ˘ ÙÔÈ¯ÒÌ·ÙÔ˜ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜, ii) ÌÂÛÔÎÔÈÏÈ·Îfi ‰È¿ÊÚ·ÁÌ· ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜, iii) ·ÚÈÛÙÂÚfi˜ ÎfiÏÔ˜, iv) ÙÂÏÔ‰È·ÛÙÔÏÈÎ‹ ‰È¿ÌÂÙÚÔ˜ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜, v) ÙÂÏÔÛ˘ÛÙÔÏÈÎ‹ ‰È¿ÌÂÙÚÔ˜ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜ Î·È vi) Ì¿˙· ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜. ‚) ∏ÏÂÎÙÚÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ·: XÚËÛÈÌÔÔÈ‹ıËÎÂ Ë Û˘ÛÎÂ˘‹ Nihon Kohden Cardiofax V. ¢. ™˘ÏÏÔÁ‹ Ô‡ÚˆÓ 24ÒÚÔ˘, Ô˘ ¯ˆÚ›ÛÙËÎÂ ÛÂ: ·) 12ˆÚË Û˘ÏÏÔÁ‹ ËÌ¤Ú·˜ Î·È ‚) 12ˆÚË Û˘ÏÏÔÁ‹ Ó‡ÎÙ·˜. ™Â Î¿ıÂ 12ˆÚË Û˘ÏÏÔÁ‹, Î·ıÒ˜ Î·È ÛÙÔ Û‡ÓÔÏÔ ÙˆÓ Ô‡ÚˆÓ 24ÒÚÔ˘, ÌÂÙÚ‹ıËÎ·Ó o fiÁÎÔ˜ ÙˆÓ Ô‡ÚˆÓ (˘ÔÏÔÁÈÛÌfi˜ Ú˘ıÌÔ‡ ‰ÈÔ‡ÚËÛË˜) Î·È Ë ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË Ô‡ÚˆÓ. ∂. √ ÁÏ˘Î·ÈÌÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÎÙÈÌ‹ıËÎÂ ÌÂ ÙË Ì¤ÙÚËÛË ÙË˜ ÁÏ˘ÎÔ˙˘ÏÈˆÌ¤ÓË˜ ·ÈÌÔÛÊ·ÈÚ›ÓË˜ HbA1c ÙËÓ ËÌ¤Ú· ÙË˜ ÌÂÏ¤ÙË˜, Î·ıÒ˜ Î·È ÙË Ì¤ÛË ÙÈÌ‹ ÙË˜ ∏b∞1c Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ 12 ÌËÓÒÓ. ™Ù·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË ∏ ÛÙ·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË ¤ÁÈÓÂ ÌÂ ÙÔ ÚfiÁÚ·ÌÌ· SPSS-PC for Windows. ŒÁÈÓÂ Û‡ÁÎÚÈÛË ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ÌÂÙ·Í‡ ‰‡Ô ÔÌ¿‰ˆÓ ‰È·‚ËÙÈÎÒÓ ·ÛıÂÓÒÓ ÌÂ ÙÔ unpaired t-test. √È Û˘Û¯ÂÙ›ÛÂÈ˜ ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ÚˆÙÂ˚ÓÔ˘Ú›·˜, ∞¶ Î·È HRV ÌÂ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ÓfiÛÔ˘ Î·È ÙËÓ ∏bA1c ¤ÁÈÓ·Ó ÌÂ ÙË ¯Ú‹ÛË ÙˆÓ Û˘Û¯ÂÙ›ÛÂˆÓ Î·Ù¿ Pearson. ∏ ‰È·‰Ô¯ÈÎ‹ ÔÏÏ·Ï‹ Û˘Û¯¤ÙÈÛË (stepwise multiple regression) ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ ÁÈ· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÛËÌ·ÓÙÈÎfiÙÂÚˆÓ ·Ú·Ì¤ÙÚˆÓ Ô˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È ÌÂ Ì›· ÌÂÙ·‚ÏËÙ‹ (.¯. ∞¶ Î·Ù¿ ÙË Ó‡ÎÙ·). ∏ ‰È¿ÌÂÛË ÙÈÌ‹ ·¤ÎÎÚÈÛË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· 12ÒÚÔ˘ (Ó‡ÎÙ·˜) ÛÂ ‰‡Ô Û˘ÏÏÔÁ¤˜ Ô‡ÚˆÓ ÙÔ˘˜ ÙÂÏÂ˘Ù·›Ô˘˜ 6 Ì‹ÓÂ˜ ‹Ù·Ó 7,5 Ìg/min. ªÂ ‚¿ÛË ·˘Ù‹ ÙËÓ ÙÈÌ‹, ¯ˆÚ›ÛÙËÎ·Ó ÔÈ ‰È·‚ËÙÈÎÔ› ¤ÊË‚ÔÈ ÛÂ 2 ÔÌ¿‰Â˜: π) ÌÂ ∞§√ ≥7,5 Ìg/min Î·È ππ) ÌÂ ∞§√ <7,5 Ìg/min.

AÔÙÂÏ¤ÛÌ·Ù· ∆· ‰ËÌÔÁÚ·ÊÈÎ¿ ÛÙÔÈ¯Â›· ÙˆÓ ÂÊ‹‚ˆÓ ÌÂ ™¢1 ÙË˜ ·ÚÔ‡Û·˜ ÌÂÏ¤ÙË˜ ‹Ù·Ó ˆ˜ ÂÍ‹˜: Ì¤ÛË ËÏÈÎ›· 16,7±4,1 ¤ÙË (Â‡ÚÔ˜: 11,0-22,0 ¤ÙË), Ì¤ÛË ËÏÈÎ›· ‰È¿ÁÓˆÛË˜ 9,3±4,2 ¤ÙË, Ì¤ÛË ‰È¿ÚÎÂÈ· ÓﬁÛÔ˘ 8,5±3,3 ¤ÙË, Ì¤ÛË ‰ﬁÛË ÙË˜ ÈÓÛÔ˘Ï›ÓË˜

435

¢È·Ù·Ú·¯¤˜ ÙÔ˘ ∞¡™ Î·È ÙË˜ ™¶ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ ÛÂ ™¢1

0,94±0,3 πU/kg/ËÌ¤Ú·. ∏ Ì¤ÛË ÙÈÌ‹ ÙË˜ HbA1c Î·Ù¿ ÙËÓ ËÌ¤Ú· ÙË˜ ÌÂÏ¤ÙË˜ ‹Ù·Ó 7,7±1,2% Î·È Ë Ì¤ÛË ÙÈÌ‹ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ 12 ÌËÓÒÓ ‹Ù·Ó 8,2±1,3%. ∏ Ì¤ÛË ÙÈÌ‹ ÙË˜ ∞¶ 24ÒÚÔ˘ ‹Ù·Ó 110,3/72,5 mmHg, ÂÓÒ Ë Ì¤ÛË ÙÈÌ‹ ∞¶ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ËÌ¤Ú·˜ ‹Ù·Ó 117,8/72,5 mmHg Î·È ÙË˜ Ó‡ÎÙ·˜ 106,4/58,7 mmHg, ·ÓÙ›ÛÙÔÈ¯·. √È ‰È·‚ËÙÈÎÔ› ¤ÊË‚ÔÈ ¯ˆÚ›ÛÙËÎ·Ó ÛÂ ‰‡Ô ÔÌ¿‰Â˜, ·Ó¿ÏÔÁ· ÌÂ ÙË ‰È¿ÌÂÛË ÙÈÌ‹ ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ Ô‡ÚˆÓ 12ÒÚÔ˘ (ÔÌ¿‰· π: ≥7,5 Ìg/min, ÔÌ¿‰· ππ: <7,5 Ìg/min). ™˘ÁÎÚ›ÓÔÓÙ·˜ ÙËÓ ÔÌ¿‰· π ÌÂ ÙËÓ ÔÌ¿‰· Iπ (¶›Ó·Î·˜ 1), ‰È·ÈÛÙÒıËÎ·Ó ˘„ËÏfiÙÂÚÂ˜ ÙÈÌ¤˜ Ì¤ÛË˜ ™¶ (109,3 vs. 106,5 mmHg, p=0,028) Î·È Ì¤ÛË˜ ¢¶ Î·Ù¿ ÙË Ó‡ÎÙ· (77,8 vs. 73,6 mmHg, p=0,035), ·ÓÙ›ÛÙÔÈ¯·. ∂›ÛË˜, ‰È·ÈÛÙÒıËÎÂ Ù·¯‡ÙÂÚÔ˜ Î·Ú‰È·Îfi˜ Ú˘ıÌfi˜ (pNN50) ÛÙËÓ ÔÌ¿‰· π Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÙËÓ ÔÌ¿‰· πI (32,9% vs. 19,9%, p<0,009). √È ‰‡Ô ÔÌ¿‰Â˜ ‰ÂÓ ‰È¤ÊÂÚ·Ó ÛÙË ‰È¿ÚÎÂÈ· ÙË˜ ÓfiÛÔ˘ ‹ ÛÙÈ˜ ÙÈÌ¤˜ ÙË˜ ∏bA1c. ™ÙË Û˘Ó¤¯ÂÈ·, ÔÈ ‰È·‚ËÙÈÎÔ› ¤ÊË‚ÔÈ ¯ˆÚ›ÛÙËÎ·Ó ÛÂ ‰‡Ô ˘ÔÔÌ¿‰Â˜, ·Ó¿ÏÔÁ· ÌÂ ÙËÓ ·Ô˘Û›· ÙÒÛË˜ (non-dippers) ‹ ÙËÓ ÙÒÛË (dippers) ÙË˜ ¢¶ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ Ó‡ÎÙ·˜ (¶›Ó·Î·˜ 2). ∏ ÌÂÙ·‚ÔÏ‹ ÙË˜ ¢¶ ›ÂÛË˜ ÙË Ó‡ÎÙ· Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÙËÓ ËÌ¤Ú· ÂÎÙÈÌ‹ıËÎÂ ÌÂ

ÙÔÓ ˘ÔÏÔÁÈÛÌfi ÙÔ˘ ËÏ›ÎÔ˘ ¢¶ Ó‡ÎÙ·˜/ËÌ¤Ú·˜. ∏ 1Ë ÔÌ¿‰· (non-dippers) ·ÚÔ˘Û›·˙Â Î·Ù¿ ÙË Ó‡ÎÙ· ˘„ËÏfiÙÂÚË ÙÈÌ‹ Ì¤ÛÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (RR) (916,0 vs. 764,4 ms, p=0,001) Î·È ˘„ËÏfiÙÂÚË ·Ú¿ÌÂÙÚÔ SDNN-i (110,6 vs. 88,1 ms, p=0,018) Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÙËÓ ÔÌ¿‰· µ, ÂÓÒ ‰ÂÓ ˘‹Ú¯Â ‰È·ÊÔÚ¿ ÛÙËÓ ·¤ÎÎÚÈÛË ÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· (∞§√). ∆Ô ËÏ›ÎÔ ÙË˜ ¢¶ Ó‡ÎÙ·˜/ËÌ¤Ú·˜ Û˘Û¯ÂÙÈ˙fiÙ·Ó ıÂÙÈÎ¿ ÌÂ ÙÔÓ Î·Ú‰È·Îfi Ú˘ıÌfi RR (r=0,49, p=0,001) Î·È ÌÂ ÙË Ó˘ÎÙÂÚÈÓ‹ ·¤ÎÎÚÈÛË ∞§√ (r=0,35, p=0,032). ∫·Ù¿ ÙË ‰ÔÎÈÌ·Û›· ÔÏÏ·Ï‹˜ ‰È·‰Ô¯ÈÎ‹˜ Û˘Û¯¤ÙÈÛË˜, Ë ÛËÌ·ÓÙÈÎfiÙË ·Ú¿ÌÂÙÚÔ˜ Ô˘ ÂËÚÂ¿˙ÂÈ ÙË ÌÂÙ·‚ÔÏ‹ ÙË˜ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Î·Ù¿ ÙË Ó‡ÎÙ· ‹Ù·Ó Ë rMSSD ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (b=0,44, p=0,001).

™˘˙‹ÙËÛË ™ÙËÓ ·ÚÔ‡Û· ÌÂÏ¤ÙË ‰È·ÈÛÙÒıËÎÂ ﬁÙÈ ¤ÊË‚ÔÈ ÌÂ ™¢1 ÌÂ ·¤ÎÎÚÈÛË ÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· ÛÙ· ·ÓÒÙÂÚ· Ê˘ÛÈÔÏÔÁÈÎ¿ ﬁÚÈ· Â›¯·Ó ˘„ËÏ‹ ¢¶ Î·Ù¿ ÙË Ó‡ÎÙ·, ·Ú¿ÏÏËÏ· ÌÂ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ∞¡™. ∞Ó¿ÏÔÁÂ˜ ÌÂÏ¤ÙÂ˜ ÛÂ ‰È·‚ËÙÈÎ¿ ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ ‰ÂÓ ˘¿Ú¯Ô˘Ó ·Ó·ÊÔÚÈÎ¿ ÌÂ ÙËÓ 24ˆÚË ‰È·Î‡Ì·ÓÛË ÙË˜ ∞¶ Î·È ÙË

¶›Ó·Î·˜ 1. ™‡ÁÎÚÈÛË ÔÌ¿‰ˆÓ ·Ó¿ÏÔÁ· ÌÂ ÙËÓ ·¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ó˘ÎÙÂÚÈÓ¿ Ô‡Ú·

HÏÈÎ›· (¤ÙË) ¢È¿ÚÎÂÈ· (¤ÙË) µªπ (kg/cm2) ∏bA1c (%) ¢fiÛË ÈÓÛÔ˘Ï›ÓË˜ (πU/kg/ËÌ¤Ú·) ª¤ÛË 24ˆÚË ™¶ (mmHg) ª¤ÛË 24ˆÚË ¢¶ (mmHg) ™¶ (Ó‡ÎÙ·˜) mmHg ¢¶ (Ó‡ÎÙ·˜) mmHg §fiÁÔ˜ ¢¶ Ó‡ÎÙ·˜/ËÌ¤Ú·˜ ª¤ÛË Ó˘ÎÙÂÚÈÓ‹ ∞§√ (Ìg/min) ªÂÙ·‚ÏËÙfiÙËÙ· Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ pNN50 (%) LF/HF

ªÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË Ô‡ÚˆÓ Ó‡ÎÙ·˜ (12ÒÚÔ˘) (≥7,5 Ìg/min) n=11 ª¤ÛË±SD

ªÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË Ô‡ÚˆÓ Ó‡ÎÙ·˜ (12ÒÚÔ˘) (<7,5 Ìg/min) n=11 ª¤ÛË±SD

16,1±3,4 8,3±3,5 22,6±2,8 8,0±1,4 0,95±0,28 112,0±11,0 65,6±9,7 109,3±11,5 77,8±6,7 0,83±15,0 14,9±4,5

19,6±4,1 8,6±3,0 21,7±2,4 8,2±1,2 0,93±0,25 108,0±6,9 62,4±5,4 106,5±8,2 73,6±6,5 0,80±12,0 3,2±1,9

0,003 ª™ M™ M™ ª™ ª™ ª™ 0,028 0,035 ª™ 0,001

32,9±14,9 1,5±0,68

19,9±17,5 2,0±1,13

0,009 0,048

™¶: ™˘ÛÙÔÏÈÎ‹ ›ÂÛË ¢¶: ¢È·ÛÙÔÏÈÎ‹ ›ÂÛË µªπ: ¢Â›ÎÙË˜ Ì¿˙·˜ ÛÒÌ·ÙÔ˜ ∞§√: ∞¤ÎÎÚÈÛË ÏÂ˘ÎˆÌ·Ù›ÓË˜ Ô‡ÚˆÓ pNN50: ¶ÔÛÔÛÙfi ÙˆÓ ‰È·ÊÔÚÒÓ ÌÂÙ·Í‡ ÙˆÓ Û˘ÓÂ¯fiÌÂÓˆÓ R-R ‰È·ÛÙËÌ¿ÙˆÓ >50 ms Î·Ù¿ ÙË Ó‡ÎÙ· ∏F/LF: ¶ËÏ›ÎÔ ¯·ÌËÏÒÓ/˘„ËÏÒÓ Û˘¯ÓÔÙ‹ÙˆÓ ÙË˜ HRV Î·Ù¿ ÙË Ó‡ÎÙ· M™: MË ÛÙ·ÙÈÛÙÈÎ¿ ÛËÌ·ÓÙÈÎfi ¶·È‰È·ÙÚÈÎ‹ 2006;69:432-439

436

∫. K·Ú·‚·Ó¿ÎË Î·È Û˘Ó.

¶›Ó·Î·˜ 2. ™‡ÁÎÚÈÛË ÔÌ¿‰ˆÓ ·Ó¿ÏÔÁ· ÌÂ ÙË ÌÂÙ·‚ÔÏ‹ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Î·Ù¿ ÙË Ó‡ÎÙ·

∏ÏÈÎ›· (¤ÙË) ¢È¿ÚÎÂÈ· ÓﬁÛÔ˘ (¤ÙË) ∏bA1c (%) BMI (kg/m2) ª¤ÛË ™¶ (Ó‡ÎÙ·) mmHg ª¤ÛË ¢¶ (Ó‡ÎÙ·) mmHg ∞§√ Ó‡ÎÙ·˜ (Ìg/min)

¶ËÏ›ÎÔ ¢¶ (¡/∏) >0,9 (non-dippers) n=6

¶ËÏ›ÎÔ ¢¶ (¡/∏) ≤0,9 (dippers) n=8

18,9±4,7 8,0±3,5 8,8±1,3 22,4±3,0 111,6±10,4 61,8±8,7 11,3±7,2

16,7±3,3 8,8±3,1 7,6±1,2 22,2±2,5 102,4±7,7 56,3±6,6 9,3±5,8

ª™ ª™ 0,004 ª™ 0,002 0,026 ª™

ª™: ™Ù·ÙÈÛÙÈÎ¿ ÌË ÛËÌ·ÓÙÈÎﬁ ¶ËÏ›ÎÔ ¢¶ (¡/∏): ¶ËÏ›ÎÔ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Ó‡ÎÙ·˜/ËÌ¤Ú·˜ ∞§√: ∞¤ÎÎÚÈÛË ÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· ™¶: ™˘ÛÙÔÏÈÎ‹ ›ÂÛË ¢¶: ¢È·ÛÙÔÏÈÎ‹ ›ÂÛË

Û˘Û¯¤ÙÈÛ‹ ÙË˜ ÌÂ ÙÔ ∞¡™, ÂÓÒ ÔÈ ÌÂÏ¤ÙÂ˜ ÙÔ˘ ∞¡™ ÌÂ ÙË Ì¤ıÔ‰Ô PSA Â›Ó·È ÔÏ‡ ÂÚÈÔÚÈÛÌ¤ÓÂ˜ ÛÙÈ˜ ËÏÈÎ›Â˜ ·˘Ù¤˜ (18-20). ∂›ÛË˜, ‰ÂÓ ¤¯ÂÈ Á›ÓÂÈ ÌÂÏ¤ÙË ÛÂ ÂÊ‹‚Ô˘˜ ÌÂ ™¢ Û¯ÂÙÈÎ¿ ÌÂ ÙËÓ Èı·Ó‹ ·ÏÏËÏÂ›‰Ú·ÛË ÙÔ˘ ∞¡™ Î·È ÙË˜ 24ˆÚË˜ ‰È·Î‡Ì·ÓÛË˜ ÙË˜ ∞¶ ÛÙËÓ ÂÌÊ¿ÓÈÛË ÙË˜ ∞§√, ÂÓÒ ·ÓÙ›ÛÙÔÈ¯Â˜ ÌÂÏ¤ÙÂ˜ ÛÂ ÂÓ‹ÏÈÎÂ˜ ÌÂ ™¢1 Â›Ó·È ÂÚÈÔÚÈÛÌ¤ÓÂ˜ (10,13,21). ™˘ÌÙˆÌ·ÙÔÏÔÁ›· ÎÏÈÓÈÎÔ‡ ∞¡™ ‰ÂÓ ÂÌÊ·Ó›˙ÂÙ·È Û˘Ó‹ıˆ˜ ÛÂ ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ ÌÂ ™¢1, fiÌˆ˜, ÂËÚÂ·ÛÌ¤ÓÔÈ ‰Â›ÎÙÂ˜ ¢∞¡ ¤¯Ô˘Ó ·Ó·ÊÂÚıÂ› ÓˆÚ›˜ ÛÙËÓ ÔÚÂ›· ÙË˜ ÓfiÛÔ˘ (10,11). ∏ ÌÂÏ¤ÙË ÙË˜ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (heart rate variability HRV) ÌÂ ÙËÓ ·Ó¿Ï˘ÛË Î·Ù¿ power spectra (PSA) Â›Ó·È Ì›· ÚfiÛÊ·ÙË Ì¤ıÔ‰Ô˜ ÌÂÏ¤ÙË˜ ÙË˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ∞¡™. ™Â ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ ÌÂ ™¢1 ¤¯ÂÈ ·Ó·ÊÂÚıÂ› Ë ‡·ÚÍË ·ıÔÏÔÁÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ∏RV (18-20), ÔÈ ÔÔ›Â˜ Û˘Û¯ÂÙ›˙ÔÓÙ·È ÌÂ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ÓfiÛÔ˘ (34) Î·È ÌÂ ÙÈ˜ ÙÈÌ¤˜ ÙË˜ HbA1c (18). ¢È·Ù·Ú·¯¤˜ ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ˘„ËÏ‹˜ (HF) Î·È ¯·ÌËÏ‹˜ Û˘¯ÓfiÙËÙ·˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (LF) ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛÙÂ› ÌÂ ÙÈ˜ ÌÂÙ·‚ÔÏ¤˜ ÙË˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘ (22), Î·ıÒ˜ Â›ÛË˜ Î·È ÌÂ Ù· Â›Â‰· ÙË˜ ÏÂ˘ÎˆÌ·Ù›ÓË˜ Ô‡ÚˆÓ 24ÒÚÔ˘ ÛÂ ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓÂ›˜ ÌÂ ·Ú¯fiÌÂÓË (22) ‹ ÂÁÎ·ÙÂÛÙËÌ¤ÓË ‰È·‚ËÙÈÎ‹ ÓÂÊÚÔ¿ıÂÈ· (23). ∞Ó¿ÏÔÁ· Â˘Ú‹Ì·Ù· ˘‹Ú¯·Ó Î·È ÛÙËÓ ·ÚÔ‡Û· ÌÂÏ¤ÙË. ™Â Ê˘ÛÈÔÏÔÁÈÎÔ‡˜ ÂÊ‹‚Ô˘˜ ¤¯ÂÈ ‰È·ÈÛÙˆıÂ› ·ÏÏËÏÂ›‰Ú·ÛË ÙÔ˘ ∞¡™ Î·È ÙË˜ ∞¶ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ 24ÒÚÔ˘ (8) Î·È ÂÈ‰ÈÎfiÙÂÚ· ·Ú·ÙËÚÂ›Ù·È ÙÒÛË ÙË˜ ∞¶ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ Ó‡ÎÙ·˜ (24). √È Spallone Î·È Û˘Ó (25) ·Ó·Ê¤ÚÔ˘Ó ÛÂ ÂÓ‹ÏÈÎÂ˜ ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓÂ›˜ ÌÂ ¢∞¡ ÙËÓ ·Ô˘Û›· Ó˘ÎÙÂÚÈÓ‹˜ ¶·È‰È·ÙÚÈÎ‹ 2006;69:432-439

ÙÒÛË˜ ÙË˜ ∞¶ Î·È ÙË Û˘Û¯¤ÙÈÛ‹ ÙË˜ ÌÂ ÙËÓ ‡·ÚÍË ·ıÔÏÔÁÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ˘„ËÏ‹˜ (HF) Î·È ¯·ÌËÏ‹˜ (LF) Û˘¯ÓfiÙËÙ·˜ ÙË˜ HRV. ™˘ÓÂÒ˜, Ë ·Ô˘Û›· ÙË˜ ÙÒÛË˜ ÙË˜ ∞¶ Î·Ù¿ ÙË Ó‡ÎÙ· ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ¢∞¡, Û˘Û¯ÂÙ›˙ÂÙ·È ÌÂ Î˘ÚÈ·Ú¯›· ÙÔ˘ Û˘Ì·ıËÙÈÎÔ‡, ÏfiÁˆ ·ÒÏÂÈ·˜ ÙÔ˘ Ó˘ÎÙÂÚÈÓÔ‡ ÙfiÓÔ˘ ÙÔ˘ ·Ú·Û˘Ì·ıËÙÈÎÔ‡ (26). ∆· Â˘Ú‹Ì·Ù· ÙË˜ ·ÚÔ‡Û·˜ ÌÂÏ¤ÙË˜ Û˘ÌÊˆÓÔ‡Ó ÌÂ ·˘Ù¿ ÙˆÓ ·ÓˆÙ¤Úˆ, ·ÊÔ‡ Ë ÔÌ¿‰· ÌÂ ˘„ËÏ‹ ¢¶ Î·Ù¿ ÙË Ó‡ÎÙ· ·ÚÔ˘Û›·˙Â ‰È·Ù·Ú·¯¤˜ ÙË˜ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ (˘„ËÏfiÙÂÚË Û˘¯ÓfiÙËÙ· RR). ∂›ÛË˜, ÙÔ ËÏ›ÎÔ ¢¶ Ó‡ÎÙ·˜/ËÌ¤Ú·˜ Û˘Û¯ÂÙÈ˙fiÙ·Ó ıÂÙÈÎ¿ ÌÂ ÙË Û˘¯ÓfiÙËÙ· ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ RR, ‰ËÏ·‰‹ ‰È·ÈÛÙÒıËÎÂ ¿ÌÂÛË Û˘Û¯¤ÙÈÛË ÙË˜ ·Ô˘Û›·˜ Ó˘ÎÙÂÚÈÓ‹˜ ÙÒÛË˜ ÙË˜ ¢¶ ÌÂ ÙËÓ ·ÚÔ˘Û›· ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ∞¡™. ¶ÚÔËÁÔ‡ÌÂÓÂ˜ ÌÂÏ¤ÙÂ˜ (13,25) ÛÂ ÂÓ‹ÏÈÎÂ˜ ÌÂ ™¢1 Èı·ÓÔÏÔÁÔ‡Ó fiÙÈ Ë ·Ô˘Û›· ÙÒÛË˜ ÙË˜ ∞¶ ÙË Ó‡ÎÙ· ÏfiÁˆ ¢∞¡, Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÂÈ‰Â›ÓˆÛË ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÚˆÙÂ˚ÓÔ˘Ú›·˜. ∞Ó¿ÏÔÁ· Â˘Ú‹Ì·Ù· ·Ó·Ê¤ÚÔÓÙ·È ÛÂ ‰È·‚ËÙÈÎÔ‡˜ ÂÊ‹‚Ô˘˜ ÌÂ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·, ÔÈ ÔÔ›ÔÈ ·ÚÔ˘Û›·˙·Ó ·‡ÍËÛË ÙË˜ ™¶ Î·Ù¿ ÙÔÓ ‡ÓÔ (7). √È Poulsen Î·È Û˘Ó (22) ·Ú·Ù‹ÚËÛ·Ó fiÙÈ ÔÈ ‰È·‚ËÙÈÎÔ› Ô˘ ·ÚÔ˘Û›·˙·Ó ·¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· ÛÙ· ·ÓÒÙÂÚ· Ê˘ÛÈÔÏÔÁÈÎ¿ Â›Â‰· Â›¯·Ó ˘„ËÏfiÙÂÚÂ˜ ÙÈÌ¤˜ ∞¶ Î·È Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ Î·Ù¿ ÙË Ó‡ÎÙ·, ·˘ÍËÌ¤ÓÔ ËÏ›ÎÔ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Ó‡ÎÙ·˜/ËÌ¤Ú·˜, Î·ıÒ˜ Î·È ·ıÔÏÔÁÈÎÔ‡˜ ‰Â›ÎÙÂ˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ∞¡™. ™˘ÓÂÒ˜, ·Ú·Ù‹ÚËÛ·Ó ÌÂÙ·‚ÔÏ¤˜ ÛÙËÓ ∞¶ Î·È ÙÔ ∞¡™ ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ (22). ∞Ó¿ÏÔÁ· Â˘Ú‹Ì·Ù· ˘‹Ú¯·Ó Î·È ÛÙËÓ ·ÚÔ‡Û· ÌÂÏ¤ÙË. ¢È·ÈÛÙÒıËÎÂ fiÙÈ Ë ˘ÔÔÌ¿‰· ÙˆÓ ‰È·‚ËÙÈÎÒÓ

437

¢È·Ù·Ú·¯¤˜ ÙÔ˘ ∞¡™ Î·È ÙË˜ ™¶ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ ÛÂ ™¢1

¶›Ó·Î·˜ 3. ∞Ó¿Ï˘ÛË ÌÂÙ·‚ÏËÙﬁÙËÙ·˜ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ Î·Ù¿ ÙË Ó‡ÎÙ·

∞. ∞Ó¿Ï˘ÛË ÛÙÔÓ ¯ÚﬁÓÔ (∆ime domain analysis) ª¤ÛË ÙÈÌ‹ RR (ms) SDNN (ms) SDNN-i (ms) SDAN-i (ms) r-MSSD (ms) pNN50 (%) µ. ∞Ó¿Ï˘ÛË Î·Ù¿ Û˘¯ÓﬁÙËÙÂ˜ (Frequency domain analysis) LF (ms.ms) HF (ms.ms) LF/HF

Non-Dippers ª¤ÛË ÙÈÌ‹±SD

Dippers ª¤ÛË ÙÈÌ‹ ±SD

916,0±129,8 183,1±56,0 110,6±27,4 137,3±54,2 117,7±42,1 36,3±15,7

764,4±103,9 175,5±94,7 88,1±35,9 125,5±62,2 83,7±43,0 28,2±20,2

0,001 ª™ 0,018 ª™ 0,008 ª™

1973±1111,3 1466,4±931,2 1,5±0,6

1599,8±960,4 1059,5±898,4 1,9±1,15

ª™ ª™ ª™

M¤ÛË ÙÈÌ‹ RR: ª¤ÛË ÙÈÌ‹ fiÏˆÓ ÙˆÓ R-R ‰È·ÛÙËÌ¿ÙˆÓ SDNN: ™Ù·ıÂÚ¿ ·fiÎÏÈÛË (SD) ÙˆÓ R-R ‰È·ÛÙËÌ¿ÙˆÓ Î·Ù¿ ÙË Ó‡ÎÙ· SDNN-i: ª¤ÛË ÙÈÌ‹ ÙˆÓ ÛÙ·ıÂÚÒÓ ·ÔÎÏ›ÛÂˆÓ fiÏˆÓ ÙˆÓ ÊÈÏÙÚ·ÚÈÛÌ¤ÓˆÓ R-R ‰È·ÛÙËÌ¿ÙˆÓ ÁÈ· fiÏ· Ù· ÙÌ‹Ì·Ù· ÙˆÓ 5 ÏÂÙÒÓ Î·Ù¿ ÙË Ó‡ÎÙ· SDAN-i: ™Ù·ıÂÚ¿ ·fiÎÏÈÛË ÙË˜ SDNN-i pNN50: ¶ÔÛÔÛÙfi ÙˆÓ ‰È·ÊÔÚÒÓ ÌÂÙ·Í‡ ÙˆÓ Û˘ÓÂ¯fiÌÂÓˆÓ R-R ‰È·ÛÙËÌ¿ÙˆÓ >50 ms Î·Ù¿ ÙË Ó‡ÎÙ· r-MSSD: TÂÙÚ·ÁˆÓÈÎ‹ Ú›˙· ÙÔ˘ Ì¤ÛÔ˘ fiÚÔ˘ ÙÔ˘ ·ıÚÔ›ÛÌ·ÙÔ˜ ÙˆÓ ÙÂÙÚ·ÁÒÓˆÓ ÙË˜ pNN50 ∏F, LF: ¶ÂÚÈÔ¯‹ ˘„ËÏÒÓ Î·È ¯·ÌËÏÒÓ Û˘¯ÓÔÙ‹ÙˆÓ ÙË˜ HRV Î·Ù¿ ÙË Ó‡ÎÙ· LF/HF: ¶ËÏ›ÎÔ ¯·ÌËÏÒÓ/˘„ËÏÒÓ Û˘¯ÓÔÙ‹ÙˆÓ ÙË˜ HRV Î·Ù¿ ÙË Ó‡ÎÙ· ª™: ™Ù·ÙÈÛÙÈÎ¿ ÌË ÛËÌ·ÓÙÈÎfi

ÌË¯·ÓÈÛÌfi˜ ÙÔ˘ ÓÂÊÚÔ‡ ÛÙËÓ ·ÚÔ˘Û›· ˘„ËÏ‹˜ ∞¶ (29). ∂ÈÏ¤ÔÓ, Ë ·ÚÔ˘Û›· ¢∞¡ ·fi ÌfiÓË ÙË˜ Û˘ÓÂ¿ÁÂÙ·È ÌÈÎÚfiÙÂÚÂ˜ Ó˘¯ıËÌÂÚfiÓ ÌÂÙ·‚ÔÏ¤˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡ Î·È ÙË˜ ∞¶, Ô˘ Ô‰ËÁÂ› ÛÂ Û¯ÂÙÈÎ‹ ˘¤ÚÙ·ÛË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ Ó‡ÎÙ·˜. ™˘ÓÂÒ˜, ˆ˜ ·ıÔÁÂÓÂÙÈÎÔ› ÌË¯·ÓÈÛÌÔ› ÙË˜ Û˘Ì‚ÔÏ‹˜ ÙË˜ ¢∞¡ ÛÙËÓ ÂÈ‰Â›ÓˆÛË ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÓÂÊÚÔ¿ıÂÈ·˜ Èı·ÓÔÏÔÁÔ‡ÓÙ·È ÔÈ ·ÎfiÏÔ˘ıÔÈ: ∏ ¢∞¡ Û˘Ì‚¿ÏÏÂÈ:

N˘ÎÙÂÚÈÓ‹ ·¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎÔÌ·Ù›ÓË˜ Ô‡ÚˆÓ (mcg/min)

ÂÊ‹‚ˆÓ ÌÂ ÔÚÈ·Î¿ ·˘ÍËÌ¤ÓË ·¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú·, Â›¯Â ˘„ËÏ¤˜ ÙÈÌ¤˜ Ì¤ÛË˜ ™¶ Î·È ¢¶ Î·Ù¿ ÙË Ó‡ÎÙ· Î·È Ù·¯‡ÙÂÚÔ Î·Ú‰È·Îfi Ú˘ıÌfi. ∂›ÛË˜, ÛÙËÓ ˘ÔÔÌ¿‰· ÙˆÓ ÂÊ‹‚ˆÓ ÌÂ ·˘ÍËÌ¤ÓË ¢¶ ÙË Ó‡ÎÙ·, ‰È·ÈÛÙÒıËÎ·Ó ·ıÔÏÔÁÈÎ¤˜ ÙÈÌ¤˜ ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ÙË˜ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ÙÔ˘ Î·Ú‰È·ÎÔ‡ Ú˘ıÌÔ‡, ¯ˆÚ›˜ ÙËÓ ‡·ÚÍË ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜. ŸÛÔÓ ·ÊÔÚ¿ ÛÙËÓ Â›‰Ú·ÛË ÙÔ˘ ∞¡™ ÛÙË ÓÂÊÚÈÎ‹ ÚÔ‹ ÙÔ˘ ·›Ì·ÙÔ˜ (renal blood flow RBF), ÌÂÏ¤ÙÂ˜ ÛÂ ‰È·‚ËÙÈÎ¿ ÔÓÙ›ÎÈ· ·Ó·Ê¤ÚÔ˘Ó fiÙÈ ÌÂÙ¿ ·fi ÓÂ˘ÚÈÎ‹ ‰È¤ÁÂÚÛË, ·˘Í¿ÓÔÓÙ·È ÔÈ ÂÚÈÊÂÚÈÎ¤˜ ·ÁÁÂÈ·Î¤˜ ·ÓÙÈÛÙ¿ÛÂÈ˜, ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙË ÌÂ›ˆÛË ÙË˜ ÓÂÊÚÈÎ‹˜ ÚÔ‹˜ ·›Ì·ÙÔ˜ (RBF) Î·È ÙËÓ ·‡ÍËÛË ÙË˜ Â·Ó·ÚÚfiÊËÛË˜ ÙÔ˘ ÓÂÚÔ‡ ·fi ÙÔ ÂÁÁ‡˜ ÂÛÂÈÚ·Ì¤ÓÔ ÛˆÏËÓ¿ÚÈÔ (27). ∞ÓÙ›ıÂÙ·, ·Ó·Ê¤ÚÂÙ·È ·˘ÍËÌ¤ÓË ‰ÈÔ‡ÚËÛË ÛÂ ‰È·‚ËÙÈÎÔ‡˜ ·ÛıÂÓÂ›˜ ÌÂ ·˘ÙfiÓÔÌË ÓÂ˘ÚÔ¿ıÂÈ· (28). ™˘ÓÂÒ˜, Â›Ó·È Èı·Ófi fiÙÈ Ë ÌÂ›ˆÛË ÙË˜ RBF Î·Ù¿ ÙËÓ ËÌ¤Ú· Î·È Ë ·‡ÍËÛ‹ ÙË˜ Î·Ù¿ ÙË Ó‡ÎÙ· ·ÔÙÂÏÔ‡Ó ÙÔÓ Û˘Ó‰ÂÙÈÎfi ÎÚ›ÎÔ ÌÂÙ·Í‡ ÙË˜ ¢∞¡ Î·È ÙË˜ ·ıÔÁ¤ÓÂÈ·˜ ‹ ÂÈ‰Â›ÓˆÛË˜ ÙË˜ ¢¡ (25). ¶Èı·ÓÔ› ·ıÔÁÂÓÂÙÈÎÔ› ÌË¯·ÓÈÛÌÔ› ÁÈ· ÙÈ˜ ‰È·Ù·Ú·¯¤˜ ·˘Ù¤˜ ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ¢∞¡ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ÂÓ‰Â¯fiÌÂÓË ÏÂÈÙÔ˘ÚÁÈÎ‹ ‰È·Ù·Ú·¯‹ ÙˆÓ ÏÂ›ˆÓ Ì˘˚ÎÒÓ ÈÓÒÓ ÙˆÓ ÚÔÛ·ÁˆÁÒÓ ·ÚÙËÚÈ‰›ˆÓ ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÛÂÈÚ¿Ì·ÙÔ˜, ÌÂ ·ÔÙ¤ÏÂÛÌ· Ó· ÂÌÔ‰›˙ÂÙ·È Ô ÚÔÛÙ·ÙÂ˘ÙÈÎfi˜

20,0

11 23

15,0

10,0

5,0

0,0 Dippers Non-dippers ¶ËÏ›ÎÔ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Î·Ù¿ ÙË Ó‡ÎÙ·

∂ÈÎﬁÓ· 1. ∞¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· ·Ó¿ÏÔÁ· ÌÂ ÙËÓ ÙÒÛË ÙË˜ ‰È·ÛÙÔÏÈÎ‹˜ ›ÂÛË˜ Î·Ù¿ ÙË Ó‡ÎÙ·. ∏ ·¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú· ‹Ù·Ó ·˘ÍËÌ¤ÓË ÛÙËÓ ÔÌ¿‰· ÙˆÓ “non-dippers” Û˘ÁÎÚÈÙÈÎ¿ ÌÂ ÙËÓ ÔÌ¿‰· ÙˆÓ “dippers”. ¶·È‰È·ÙÚÈÎ‹ 2006;69:432-439

438

∫. K·Ú·‚·Ó¿ÎË Î·È Û˘Ó.

·) ÛÙË ÌÂ›ˆÛË ÙË˜ ÙÒÛË˜ ÙË˜ ∞¶ Î·Ù¿ ÙË Ó‡ÎÙ·, ‚) ÛÙËÓ ·‡ÍËÛË ÙË˜ RBF Î·È Á) ÛÙË ÌÂ›ˆÛË ÙË˜ Â·Ó·ÚÚfiÊËÛË˜ ÓÂÚÔ‡ ·fi ÙÔ ÂÁÁ‡˜ ÂÛÂÈÚ·Ì¤ÓÔ ÛˆÏËÓ¿ÚÈÔ (25). √È ·Ú·¿Óˆ ·ÈÌÔ‰˘Ó·ÌÈÎ¤˜ ÌÂÙ·‚ÔÏ¤˜ ÛÙÔÓ ÓÂÊÚfi Â›Ó·È Èı·Ófi fiÙÈ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ¤Ó·ÚÍË ‹ ÙËÓ ÂÈ‰Â›ÓˆÛË ÙË˜ ‰È·‚ËÙÈÎ‹˜ ÚˆÙÂ˚ÓÔ˘Ú›·˜. ™˘ÌÂÚ·ÛÌ·ÙÈÎ¿, ‰È·ÈÛÙÒıËÎÂ fiÙÈ ‰È·‚ËÙÈÎÔ› ¤ÊË‚ÔÈ ¯ˆÚ›˜ ˘¤ÚÙ·ÛË Î·È ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›· ÌÔÚÂ› Ó· ÂÌÊ·Ó›˙Ô˘Ó ÔÚÈ·Î¿ ·˘ÍËÌ¤ÓË ·¤ÎÎÚÈÛË ÌÈÎÚÔÏÂ˘ÎˆÌ·Ù›ÓË˜ ÛÙ· Ô‡Ú·, ·Ú¿ÏÏËÏ· ÌÂ ÙËÓ ·Ô˘Û›· ÙÒÛË˜ ÙË˜ ∞¶ Î·Ù¿ ÙË Ó‡ÎÙ· Î·ıÒ˜ Î·È ÌÂ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ∞¡™. ∏ ¤ÁÎ·ÈÚË ‰È¿ÁÓˆÛË ÙË˜ ·Ô˘Û›·˜ ÙÒÛË˜ ∞¶ Î·Ù¿ ÙË Ó‡ÎÙ· ıÂˆÚÂ›Ù·È ÚÔÁÓˆÛÙÈÎfi˜ ‰Â›ÎÙË˜ ÌÂÏÏÔÓÙÈÎ‹˜ ÂÌÊ¿ÓÈÛË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ Î·È ¢¡ (30). ™˘ÓÂÒ˜, Ë ¤ÁÎ·ÈÚË ·Ó›¯ÓÂ˘ÛË ‰È·‚ËÙÈÎÒÓ ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ ÌÂ ˘„ËÏ‹ ∞¶ ÙË Ó‡ÎÙ· ı· ÌÔÚÔ‡ÛÂ Ó· Û˘Ì‚¿ÏÂÈ ÛÙËÓ ÚfiÏË„Ë ÙË˜ ÂÌÊ¿ÓÈÛË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜, ÌÂ ÙË ¯Ú‹ÛË ÂÓ‰Â¯ÔÌ¤Óˆ˜ Ê·ÚÌ·ÎÂ˘ÙÈÎ‹˜ ·ÁˆÁ‹˜.

10.

11.

12.

13.

14.

15.

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24.

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¢È·Ù·Ú·¯¤˜ ÙÔ˘ ∞¡™ Î·È ÙË˜ ™¶ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙË˜ ÌÈÎÚÔÏÂ˘ÎˆÌ·ÙÈÓÔ˘Ú›·˜ ÛÂ ™¢1

in normotensive and normoalbuminuric Type 1 diabetic patients. Diabetes Res Clin Pract 2001;53:85-90. 25. Spallone V, Gambardella S, Maiello MR, Barini A, Frontoni S, Menzinger G. Relationship between autonomic neuropathy, 24-h blood pressure profile, and nephropathy in normotensive IDDM patients. Diabetes Care 1994;17:578-584. 26. Pontuch P, Vozar J, Potocky M, Krahulec B. Relationship between nephropathy, retinopathy, and autonomic neuropathy in patients with type 1 diabetes. J Diabet Complications 1990;4:188-192. 27. Bello-Reuss E, Pastoriza-Munoz E, Colindres RE. Acute unilateral renal denervation in rats with extracellular volume expansion. Am J Physiol 1977; 232:F26-F32.

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¶·È‰È·ÙÚÈÎ‹ 2006;69:432-439

440

∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞

ORIGINAL ARTICLE

™˘Û¯¤ÙÈÛË Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜ Î·È ÎÏÈÓÈÎ‹˜ Î·Ù¿ÛÙ·ÛË˜ ·ÛıÂÓÒÓ ÌÂ Î˘ÛÙÈÎ‹ ›ÓˆÛË 1 ¢’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ∞.¶.£., ¡ÔÛÔÎÔÌÂ›Ô ¶··ÁÂˆÚÁ›Ô˘, £ÂÛÛ·ÏÔÓ›ÎË 2 ∂ÚÁ·ÛÙ‹ÚÈÔ ∂ÚÁÔÌÂÙÚ›·˜, ∆∂º∞∞, ∞.¶.£. £ÂÛÛ·ÏÔÓ›ÎË AÏÏËÏÔÁÚ·Ê›·: ∆·ÙÈ·Ó‹ ªÔ‡‰ÈÔ˘ ∞Á›·˜ ™ÔÊ›·˜ 9, ∆.∫. 570 10, ¶Â‡Î· £ÂÛÛ·ÏÔÓ›ÎË˜ E-mail: tmod@med.auth.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 10-02-2006 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 05-09-2006

∆. ªÔ‡‰ÈÔ˘1, ∞. °·ÏÏ‹ - ∆ÛÈÓÔÔ‡Ïo˘1, ∂. µ·Ì‚·ÎÔ‡‰Ë˜2, ™. ¡Ô‡ÛÈ· - ∞Ú‚·ÓÈÙ¿ÎË1

¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: ∏ Î·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ÛÙËÓ ËÚÂÌ›· Î·Ï‡ÙÂÈ ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ Ì¤ÚÔ˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈ-

ÛÌÔ‡ ÛÙÔÓ ¿ÓıÚˆÔ. À¿Ú¯Ô˘Ó ÔÏÏÔ› ·Ú¿ÁÔÓÙÂ˜ ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ÂËÚÂ¿˙ÂÙ·È Ë Î·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜. ™ÎÔfi˜ ÙË˜ ·ÚÔ‡Û·˜ ÌÂÏ¤ÙË˜ ‹Ù·Ó Ë Û˘Û¯¤ÙÈÛË ÙË˜ Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜ ÛÂ ËÚÂÌ›· (KEH) ÌÂ ÙËÓ ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË ·ÛıÂÓÒÓ ÌÂ Î˘ÛÙÈÎ‹ ›ÓˆÛË (∫π) ¯ˆÚ›˜ ÚfiÛÊ·ÙË ÏÔ›ÌˆÍË. ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ∏ ∫∂∏ ÌÂÙÚ‹ıËÎÂ ÌÂ ÙË Ì¤ıÔ‰Ô ÙË˜ ¤ÌÌÂÛË˜ ıÂÚÌÈ‰ÔÌÂÙÚ›·˜ ÛÂ Ì›· ÔÌ¿‰· 38 ·ÛıÂÓÒÓ ÌÂ ∫π Î·È ÂÍÂÙ¿ÛÙËÎÂ Ë Û¯¤ÛË ÙË˜ ÌÂ ÙËÓ ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· Î·È ÙËÓ ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË ÙˆÓ ·ÛıÂÓÒÓ. °È· ÙËÓ ÂÎÙ›ÌËÛË ÙË˜ ·Ó·ÓÂ˘ÛÙÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÌÂÙÚ‹ıËÎ·Ó ÌÂ ÛÈÚÔÌÂÙÚ›· Ë FEV1, Ë FVC Î·È Ë PEFR, ÂÓÒ Ë ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË ÚÔÛ‰ÈÔÚ›ÛÙËÎÂ ·fi ÙÔÓ ‰Â›ÎÙË Schwachman. ∞ÔÙÂÏ¤ÛÌ·Ù·: ™ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π, ÛÂ Û‡ÁÎÚÈÛË ÌÂ ˘ÁÈ‹ ¿ÙÔÌ·, ‚Ú¤ıËÎÂ ·˘ÍËÌ¤ÓË ∫∂∏, ÂÎÊÚ·ÛÌ¤ÓË ˆ˜ ÔÛÔÛÙfi ÙË˜ ÚÔ‚ÏÂfiÌÂÓË˜ ∫∂∏ (∫∂∏%), (110,96±2,35%, p=0,001). ∏ ·‡ÍËÛË ·˘Ù‹ ·Ú·ÙËÚ‹ıËÎÂ Î·È ÛÙ· ‰‡Ô Ê‡Ï·. ∂›ÛË˜, ˘¿Ú¯ÂÈ ÈÛ¯˘Ú‹ Û˘Û¯¤ÙÈÛË ÙË˜ ∫∂∏% ÌÂ ÙÔÓ ‰Â›ÎÙË Schwachman ÙˆÓ ·ÛıÂÓÒÓ (r=-0,654, p=0,0001) Î·È ÙËÓ Î·Ù¿ÛÙ·ÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘˜ (FEV1: r=-0,475, p=0,003 Î·È FVC: r=-0,57, p=0,0001). ™˘ÌÂÚ¿ÛÌ·Ù·: ™˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÙÔ ÔÛÔÛÙfi ÙË˜ ÚÔ‚ÏÂfiÌÂÓË˜ ∫∂∏ Â›Ó·È ÈÎ·Ófi Ó· ÛÙ·ıÂ› ˆ˜ ‰Â›ÎÙË˜ ‚·Ú‡ÙËÙ·˜ ÙË˜ ÓfiÛÔ˘. ∂ÈÏ¤ÔÓ, Û˘ÓÈÛÙ¿Ù·È Ë Ì¤ÙÚËÛË ÙË˜ ∫∂∏% ÛÙÔÓ ÂÙ‹ÛÈÔ ¤ÏÂÁ¯Ô ÙˆÓ ·ÛıÂÓÒÓ ÌÂ ∫π.

§¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ∫˘ÛÙÈÎ‹ ›ÓˆÛË, Î·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜.

Relation of resting energy expenditure with the clinical condition in cystic fibrosis patients 1 4th Department of Pediatrics, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki 2 Ergophysiology and Ergometry Laboratory, Faculty of Physical Education and Sport Science, Aristotle University of Thessaloniki Correspondence: Tatiani Moudiou 9, Agias Sofias Str. 57010 Pefka, Thessaloniki E-mail: tmod@med.auth.gr Date of submission: 10-02-2006 Date of approval: 05-09-2006

T. Moudiou1, A. Galli - Tsinopoulou1, E. Vamvakoudis2, S. Nousia - Arvanitakis1

Abstract: Background: Resting energy expenditure (REE) is the main component of human metabolism. There are many factors affecting energy expenditure. The purpose of this study was to investigate the relationship of REE with the clinical condition of cystic fibrosis (CF) patients without active infection. The issue whether REE can serve alone as an indicator of the disease severity was addressed. Methods: REE was measured with indirect calorimetry in a group of 38 CF patients and its correlation with pulmonary function assessed with FEV1 and FVC, and clinical status assessed with Schwachman score was studied. Results: An increased REE expressed as a percentage of predicted REE (REE%) was found in CF

patients, compared to healthy (110.96±2.35%, p=0.001). REE was not affected by gender differences and exhibited a strong correlation with Schwachman score (r=-0.654, p=0.0001) and pulmonary function (FEV1: r=-0.475, p=0.003 and FVC: r=-0.57, p=0.0001) of the patients. Conclusions: This data analysis revealed that the percentage of predicted REE can serve alone as an indicator of disease severity. The use of REE% on yearly clinical follow up of the CF patient is recommended.

Key words: Cystic fibrosis, resting energy expenditure.

¶·È‰È·ÙÚÈÎ‹ 2006;69:440-446

441

∫·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜ ÛÙËÓ Î˘ÛÙÈÎ‹ ›ÓˆÛË

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ ∫∂∏ ∫π ¢ª™

∫·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜ ∫˘ÛÙÈÎ‹ ›ÓˆÛË ¢Â›ÎÙË˜ Ì¿˙·˜ ÛÒÌ·ÙÔ˜

∂ÈÛ·ÁˆÁ‹ ∏ ˘ÔıÚÂ„›· ·ÔÙÂÏÂ› ÌÈ· Û˘¯Ó‹ ÎÏÈÓÈÎ‹ ÂÎ‰‹ÏˆÛË ÙË˜ ∫π, Ë ÔÔ›· ·Ô‰fiıËÎÂ ÛÙÔ ·ÚÂÏıfiÓ Î˘Ú›ˆ˜ ÛÙËÓ ·ÓÂ·ÚÎ‹ ÚfiÛÏË„Ë ÙÚÔÊ‹˜ Î·È ÛÙËÓ ÏËÌÌÂÏ‹ ·ÔÚÚfiÊËÛË (1). ∏ Û‡Á¯ÚÔÓË, fiÌˆ˜, ıÂÚ·Â›· ÌÂ ˘ÔÎ·Ù¿ÛÙ·Ù· ÌÈÎÚÔÛÊ·ÈÚÈÎÒÓ ·ÁÎÚÂ·ÙÈÎÒÓ ÂÓ˙‡ÌˆÓ, Ë ÔÔ›· Ô‰ËÁÂ› ÛÙËÓ Î·Ï‡ÙÂÚË ·ÔÚÚfiÊËÛË, ÛÂ Û˘Ó‰˘·ÛÌfi ÌÂ ‰›·ÈÙÂ˜ ˘„ËÏ‹˜ ÂÓ¤ÚÁÂÈ·˜, ı· ¤ÚÂÂ Ó· Â›¯Â ·ÓÙÈÌÂÙˆ›ÛÂÈ ÙÔ Úfi‚ÏËÌ· ÙË˜ ˘ÔıÚÂ„›·˜ ÛÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π. ¶·Ú’ fiÏ· ·˘Ù¿, ÛÙÔ 20% ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ, ÙÔ ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ ÂÍ·ÎÔÏÔ˘ıÂ› Ó· ‚Ú›ÛÎÂÙ·È Î¿Ùˆ ·fi ÙËÓ 5Ë ÂÎ·ÙÔÛÙÈ·›· ı¤ÛË (2). ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ë Î·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ÂËÚÂ¿˙ÂÙ·È ·fi ‰È¿ÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙÂ˜, fiˆ˜ ÙÔ ‚¿ÚÔ˜ ÛÒÌ·ÙÔ˜ Î·È È‰È·›ÙÂÚ· ÙÔ ÔÛÔÛÙfi Ì˘˚Î‹˜ Ì¿˙·˜ ÛÒÌ·ÙÔ˜, fiÔ˘ Î˘Ú›ˆ˜ Î·Ù·Ó·ÏÒÓÂÙ·È ÙÔ ÔÍ˘ÁfiÓÔ. ∂›ÛË˜, Ë ¯ÚfiÓÈ· ÓÂ˘ÌÔÓÔ¿ıÂÈ· ·ÔÙÂÏÂ› ÛËÌ·ÓÙÈÎfi ·Ú¿ÁÔÓÙ·, Ô ÔÔ›Ô˜ Ô‰ËÁÂ› ÛÂ ˘ÂÚÌÂÙ·‚ÔÏÈÛÌfi. ™ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π Î·È ÂÈ‚·Ú˘Ì¤ÓË ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›·, ÙÔ ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ Î·È Ë Ì˘˚Î‹ Ì¿˙· Â›Ó·È Û˘Ó‹ıˆ˜ ÂÏ·ÙÙˆÌ¤Ó·. ∏ Û˘ÓÔÏÈÎ‹ Î·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ∫π Î·È Ì¤ÙÚÈ· ÂÈ‚¿Ú˘ÓÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ ¤¯ÂÈ ·Ó·ÊÂÚıÂ› fiÙÈ Â›Ó·È Û˘ÁÎÚ›ÛÈÌË ÌÂ ÂÎÂ›ÓË ÛÙÔÓ ˘ÁÈ‹ ÏËı˘ÛÌfi, ·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë ∫∂∏ ‚Ú¤ıËÎÂ ·˘ÍËÌ¤ÓË (3-5). ∏ ∫∂∏ ·ÔÙÂÏÂ› Ù· ‰‡Ô ÙÚ›Ù· ÙË˜ ËÌÂÚ‹ÛÈ·˜ Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜. ∆Ô ˘fiÏÔÈÔ ¤Ó· ÙÚ›ÙÔ Â›Ó·È ÙÔ ¿ıÚÔÈÛÌ· ÙË˜ Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜, ÙÔ ÔÔ›Ô Û¯ÂÙ›˙ÂÙ·È ÌÂ ÙË Ê˘ÛÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ·, ÙË ıÂÚÌÔÁ¤ÓÂÛË Î·È ÙË ÛˆÌ·ÙÈÎ‹ ·‡ÍËÛË ÛÙ· ·È‰È¿ (6). À¿Ú¯ÂÈ, ˆÛÙfiÛÔ, ‰È·ÊˆÓ›· ÛÙË Û¯¤ÛË ÙË˜ ∫∂∏ ÌÂ ÙËÓ ¤Í·ÚÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÓfiÛÔ˘ ÛÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π. ∫¿ÔÈÂ˜ ÌÂÏ¤ÙÂ˜ (5,7,8) ‰Â›¯ÓÔ˘Ó ·‡ÍËÛË ÙË˜ ∫∂∏ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ¤Í·ÚÛË˜ ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÓfiÛÔ˘, ÂÓÒ ¿ÏÏÂ˜ fi¯È (9). ∂›ÛË˜, ˘¿Ú¯Ô˘Ó ÌÂÏ¤ÙÂ˜ ÛÙÈ˜ ÔÔ›Â˜ ÂÍÂÙ¿˙ÂÙ·È Ë ∫∂∏ ÛÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π, ÔÈ ÔÔ›ÔÈ ‰ÂÓ ¤¯Ô˘Ó ÚfiÛÊ·ÙË ÏÔ›ÌˆÍË (5,10,11). ™‡ÌÊˆÓ· ÌÂ ÙÈ˜ ÌÂÏ¤ÙÂ˜ ·˘Ù¤˜, Ë ∫∂∏ Â›Ó·È ·˘ÍËÌ¤ÓË ÛÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π ÛÂ Û‡ÁÎÚÈÛË ÌÂ ·ÓÙ›ÛÙÔÈ¯Ë ÔÌ¿‰· ˘ÁÈÒÓ ·ÙfiÌˆÓ ‹ ÌÂ ÙÈÌ¤˜ Ô˘ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÂÍÈÛÒÛÂÈ˜, ÔÈ ÔÔ›Â˜ ÂÚÈÁÚ¿ÊÔ˘Ó ·ÓÙ›-

ÛÙÔÈ¯Ô ˘ÁÈ‹ ÏËı˘ÛÌfi. ¢ÂÓ ¤¯ÂÈ, fiÌˆ˜, ‰ÈÂ˘ÎÚÈÓÈÛÙÂ› Â¿Ó Ë ·‡ÍËÛË ÙË˜ ∫∂∏, Ë ÔÔ›· ·Ó·Ê¤ÚÂÙ·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·, ÔÊÂ›ÏÂÙ·È ÛÙËÓ ¤Í·ÚÛË ÙË˜ ÏÔ›ÌˆÍË˜, ÛÙË ¯ÚfiÓÈ· ÊÏÂÁÌÔÓ‹, ÛÙË ÁÔÓÈ‰È·Î‹ ‚Ï¿‚Ë ‹ ÛÙËÓ ÂÈ‚¿Ú˘ÓÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ (12,13). ™ÎÔfi˜ ÙË˜ ·ÚÔ‡Û·˜ ÌÂÏ¤ÙË˜ ‹Ù·Ó Ó· ·ÔÛ·ÊËÓ›ÛÂÈ ÙË Û¯¤ÛË ÙË˜ ∫∂∏ ÌÂ ÙËÓ ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ∫π, ÔÈ ÔÔ›ÔÈ ‹Ù·Ó ÎÏÈÓÈÎ¿ ÛÙ·ıÂÚÔ› Î·È ‰ÂÓ Â›¯·Ó ¤Í·ÚÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÓfiÛÔ˘. ∂›ÛË˜, Ë ÌÂÏ¤ÙË ·˘Ù‹ ·ÔÛÎÔÂ› ÛÙÔ Ó· ‰ÈÂÚÂ˘Ó‹ÛÂÈ Î·Ù¿ fiÛÔÓ Ë ∫∂∏ ÌÔÚÂ› Ó· ¯ÚËÛÈÌÔÔÈËıÂ› ˆ˜ ‰Â›ÎÙË˜ ‚·Ú‡ÙËÙ·˜ ÙË˜ ÓfiÛÔ˘ ÙË˜ ∫π.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ªÂÏÂÙ‹ıËÎ·Ó 38 ·ÛıÂÓÂ›˜ ÌÂ ∫π, 19 ·ÁfiÚÈ· Î·È 19 ÎÔÚ›ÙÛÈ·, ËÏÈÎ›·˜ 9-35 ÂÙÒÓ, ÌÂ Ì¤ÛÔ fiÚÔ ËÏÈÎ›·˜ Ù· 19,72±1,0 ¤ÙË. √È ·ÛıÂÓÂ›˜ ·˘ÙÔ› ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·Ó Ù·ÎÙÈÎ¿ ·fi ÙÔ ÂÍˆÙÂÚÈÎfi È·ÙÚÂ›Ô ∫π. √ ¤ÏÂÁ¯Ô˜ ¤ÁÈÓÂ ÛÂ ÂÚ›Ô‰Ô Î·Ù¿ ÙËÓ ÔÔ›· ÔÈ ·ÛıÂÓÂ›˜ ‹Ù·Ó ÛÂ Î·Ï‹ ÁÂÓÈÎ‹ Î·Ù¿ÛÙ·ÛË, ¯ˆÚ›˜ Á·ÛÙÚÔÛÙÔÌ›· ‹ ·ÚÂÓÙÂÚÈÎ‹ ‰È·ÙÚÔÊ‹ Î·È Î·ÓÂ›˜ ‰ÂÓ Â›¯Â ¤Í·ÚÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÓfiÛÔ˘. ∏ ·ÍÈÔÏfiÁËÛË ÙË˜ ÎÏÈÓÈÎ‹˜ ÙÔ˘˜ Î·Ù¿ÛÙ·ÛË˜, fiˆ˜ ÂÎÊÚ¿˙ÂÙ·È ·fi ÙË ‚·ıÌÔÏfiÁËÛË Î·Ù¿ Shwachman, ‹Ù·Ó ·fi 74 ¤ˆ˜ 96 (Ì¤ÛÔ˜ fiÚÔ˜: 87,0±1,18). ∞fi ÙÔ Û‡ÓÔÏÔ ÙˆÓ 38 ·ÛıÂÓÒÓ ÌÂ ∫π, ÔÈ 6 Â›¯·Ó ·ÁÎÚÂ·ÙÈÎ‹ Â¿ÚÎÂÈ· (¶∂). ŸÏÔÈ ÔÈ ·ÛıÂÓÂ›˜ ÌÂ ·ÁÎÚÂ·ÙÈÎ‹ ·ÓÂ¿ÚÎÂÈ· (¶∞) ‚Ú›ÛÎÔÓÙ·Ó ÛÂ ıÂÚ·Â›· ˘ÔÎ·Ù¿ÛÙ·ÛË˜ ÌÂ ·ÁÎÚÂ·ÙÈÎ¿ ¤Ó˙˘Ì·. ∞fi ÙÔ˘˜ 38 ·ÛıÂÓÂ›˜, ÔÈ 32 Â›¯·Ó ·ÔÈÎÈÛÙÂ› ÌÂ „Â˘‰ÔÌÔÓ¿‰· Î·È ·ÎÔÏÔ˘ıÔ‡Û·Ó ÙÔ ÚˆÙfiÎÔÏÏÔ ıÂÚ·Â›·˜ ÌÂ ÂÈÛÓÂfiÌÂÓ· ·ÓÙÈ„Â˘‰ÔÌÔÓ·‰ÈÎ¿ ·ÓÙÈ‚ÈÔÙÈÎ¿. ∏ ¤ÏÏÂÈ„Ë ¤Í·ÚÛË˜ ÙË˜ ÓfiÛÔ˘ ÂÈ‚Â‚·ÈÒıËÎÂ ÌÂ ÙË Ê˘ÛÈÎ‹ ÂÍ¤Ù·ÛË ÙˆÓ ·ÛıÂÓÒÓ Î·È ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ÌÂ ·ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·Î·, CRP Î·È ÙÔÓ ·ÚÈıÌfi ÙˆÓ ÏÂ˘ÎÔÎ˘ÙÙ¿ÚˆÓ. ∫·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ÛÙËÓ ËÚÂÌ›· (∫∂∏) ∏ ∫∂∏ ÌÂÙÚ‹ıËÎÂ ÌÂ ¤ÌÌÂÛË ıÂÚÌÈ‰ÔÌÂÙÚ›· (JAEGER EOS-Sprint Oxygen Analyzer, Würzburg, Germany) Î·Ù¿ ÙÈ˜ ÚˆÈÓ¤˜ ÒÚÂ˜, ÌÂÙ¿ ·fi ÔÏÔÓ‡ÎÙÈ· ·Ó¿·˘ÛË ÌÂ ‡ÓÔ. ∏ ‰ÔÎÈÌ·Û›· ¤ÁÈÓÂ ÛÂ ¤Ó· ‰ˆÌ¿ÙÈÔ ‹Û˘¯Ô Î·È ıÂÚÌÈÎ¿ Ô˘‰¤ÙÂÚÔ. √ ·ÛıÂÓ‹˜ ‚ÚÈÛÎfiÙ·Ó ÛÂ ‡ÙÈ· ı¤ÛË, ‹Ù·Ó ‹ÚÂÌÔ˜, ¯ˆÚ›˜ Ó· ÎÔÈÌ¿Ù·È ÂÚ›Ô˘ Â› 15 ÏÂÙ¿, ÚÈÓ ·Ú¯›ÛÂÈ Ë ‰ÔÎÈÌ·Û›·, ÚÔÎÂÈÌ¤ÓÔ˘ Ó· ÂÍÔÈÎÂÈˆıÂ› ÌÂ ÙÔÓ ¯ÒÚo Î·È Ó· Á›ÓÂÈ ÂÂÍ‹ÁËÛË ÙË˜ ‰È·‰ÈÎ·Û›·˜. ™ÙË Û˘Ó¤¯ÂÈ·, ÂÈ‰ÈÎfi ÚÈÓÔ›ÂÛÙÚÔ Î·È ÂÈ‰ÈÎfi ÂÈÛÙfiÌÈÔ ÚÔÛ·ÚÌfi˙ÔÓÙ·Ó ÛÙÔÓ ·ÛıÂÓ‹. √ ÂÎÓÂfiÌÂÓÔ˜ ·¤Ú·˜ ‰ÈÔ¯ÂÙÂ˘fiÙ·Ó ·fi Ì›· ‚·Ï‚›‰· ˘„ËÏ‹˜ Ù·¯‡ÙËÙ·˜ (Hans Rudolf) ‰È·Ì¤ÛÔ˘ ÂÓfi˜ Ï·ÛÙÈÎÔ‡ ÛˆÏ‹Ó· ¯·ÌËÏ‹˜ ·ÓÙ›ÛÙ·ÛË˜ ÛÂ ¤Ó· Û¿ÎÔ ·Ó¿ÌÂÈÍË˜ ·ÂÚ›ˆÓ 7 Ï›ÙÚˆÓ. ÃÚËÛÈÌÔÔÈ‹ıËÎÂ Ë Ì¤ıÔ‰Ô˜ ·Ó¿Ï˘ÛË˜ ·ÂÚ›ˆÓ ÛÂ Î¿ıÂ ·Ó·ÓÔ‹ Î·È ˘‹Ú¯Â Ô Ì¤ÛÔ˜ fiÚÔ˜ ÙˆÓ ÙÈÌÒÓ Î¿ıÂ 35 sec. √È ·ÙÌÔÛÊ·ÈÚÈÎ¤˜ Û˘Óı‹ÎÂ˜ ıÂÚÌÔÎÚ·Û›·˜ Î·È ›ÂÛË˜ Î·Ù·ÁÚ¿ÊÔÓÙ·Ó. √È ÂÛˆÙÂÚÈÎÔ› ·ÈÛıËÙ‹ÚÂ˜ ÙÔ˘ ÌË¯·Ó‹Ì·ÙÔ˜ ÂÏ¤Á¯ÔÓÙ·Ó ¿ÓÙ· ÚÈÓ ·fi ÙË ‰ÔÎÈÌ·Û›· ÁÈ· ÙËÓ ÂÏ¿ÙÙˆÛË ÙË˜ Èı·ÓfiÙËÙ·˜ ¶·È‰È·ÙÚÈÎ‹ 2006;69:440-446

442

∆. ªÔ‡‰ÈÔ˘ Î·È Û˘Ó.

Ï¿ıÔ˘˜. √È ·ÛıÂÓÂ›˜ ÚÈÓ ·fi ÙË ‰ÔÎÈÌ·Û›· ‹Ù·Ó ÓËÛÙÈÎÔ›, ·ÏÏ¿ Â›¯·Ó Ï¿‚ÂÈ fiÏ· Ù· Ê¿ÚÌ·Î¿ ÙÔ˘˜, ÂÎÙfi˜ ·fi Ù· ‚2 ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈÎ¿, ÁÈ· Ù· ÔÔ›· ‰fiıËÎÂ Ô‰ËÁ›· Ó· ‰È·ÎÔÔ‡Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ ÁÈ· 12 ÒÚÂ˜. √ ÂÎÓÂfiÌÂÓÔ˜ fiÁÎÔ˜ ·¤Ú· ÌÂÏÂÙ‹ıËÎÂ Â› 25 ÏÂÙ¿. ∏ ÛÙ·ıÂÚ‹ Î·Ù¿ÛÙ·ÛË ·ÂÚÈÛÌÔ‡ ıÂˆÚÔ‡ÓÙ·Ó fiÙÈ ÂÈÙÂ‡¯ıËÎÂ fiÙ·Ó Ô Ì¤ÛÔ˜ fiÚÔ˜ ÌÂÙ·‚ÔÏÒÓ ÙË˜ VO2 Î·È VCO2 ‹Ù·Ó ÏÈÁfiÙÂÚÔ ·fi 10% Î·È Ô Ì¤ÛÔ˜ fiÚÔ˜ ÌÂÙ·‚ÔÏÒÓ ÙÔ˘ ·Ó·ÓÂ˘ÛÙÈÎÔ‡ ËÏ›ÎÔ˘ ‹Ù·Ó ÌÈÎÚfiÙÂÚÔ˜ ·fi 5% (14-16). ∞˘Ùfi ÂÈÙÂ‡¯ıËÎÂ ÛÙ· ÚÒÙ· 5 ÏÂÙ¿ ÙË˜ Ì¤ÙÚËÛË˜ ÛÂ fiÏÂ˜ ÙÈ˜ ÂÚÈÙÒÛÂÈ˜. ∞Ó ‰ÂÓ ‹Ù·Ó ÂÊÈÎÙ‹ Ë Î·Ù¿ÛÙ·ÛË ÈÛÔÚÚÔ›·˜, Ë ‰ÔÎÈÌ·Û›· Â·Ó·Ï·Ì‚·ÓfiÙ·Ó ¿ÏÏË ËÌ¤Ú·. ™Â fiÏË ÙË ‰È¿ÚÎÂÈ· ÙË˜ ‰ÔÎÈÌ·Û›·˜ ˘‹Ú¯Â Â›‚ÏÂ„Ë. √È ÌÂÙÚ‹ÛÂÈ˜ ·Ì¤Ûˆ˜ ÌÂÙ¿ ·fi ÂÂÈÛfi‰ÈÔ ‚‹¯· ‹ ÎÈÓ‹ÛÂˆÓ ÙÔ˘ ÛÒÌ·ÙÔ˜, ÂÍ·ÈÚ¤ıËÎ·Ó. ∂›ÛË˜, Ù· ‰Â‰ÔÌ¤Ó· ÙˆÓ ÚÒÙˆÓ 5 ÏÂÙÒÓ ‰ÂÓ Ï·Ì‚¿ÓÔÓÙ·Ó ˘’ fi„ÈÓ. ∞fi ÙÈ˜ ÌÂÙÚ‹ÛÂÈ˜ ÙˆÓ ˘fiÏÔÈˆÓ 20 ÏÂÙÒÓ ˘ÔÏÔÁ›ÛÙËÎÂ Ô Ì¤ÛÔ˜ fiÚÔ˜ ÁÈ· ÙÔ Î·Ù·Ó·ÏÔ‡ÌÂÓÔ √2 (VO2) Î·È ÙÔ ÂÎÓÂfiÌÂÓÔ ‰ÈÔÍÂ›‰ÈÔ ÙÔ˘ ¿ÓıÚ·Î· (VCO2). °È· ÙÔÓ ˘ÔÏÔÁÈÛÌfi ÙË˜ ∫∂∏ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ÂÍ›ÛˆÛË ÙÔ˘ Weir (17,18) ∫∂∏ = [3,941*VO2+1,11*VCO2]*1,44. ™ÙË ‰È¿ÚÎÂÈ· ÙË˜ ÌÂÏ¤ÙË˜, ÙÚÂÈ˜ ·ÛıÂÓÂ›˜ ¯ÚÂÈ¿ÛÙËÎÂ Ó· Â·Ó·Ï¿‚Ô˘Ó ÙË ‰ÔÎÈÌ·Û›·. ∏ ∫∂∏ ÂÎÊÚ¿ÛÙËÎÂ ÛÂ ıÂÚÌ›‰Â˜ ·Ó¿ ËÌ¤Ú· Î·È ¤ÁÈÓÂ Û‡ÁÎÚÈÛË ÌÂ ÚÔ‚ÏÂfiÌÂÓÂ˜ ÙÈÌ¤˜ ÁÈ· ÙÔ Ê‡ÏÔ, ÙËÓ ËÏÈÎ›·, ÙÔ ‚¿ÚÔ˜ Î·È ÙÔ ‡„Ô˜, ÔÈ ÔÔ›Â˜ ˘ÔÏÔÁ›ÛÙËÎ·Ó ·fi ÙÈ˜ ÂÍÈÛÒÛÂÈ˜ ÙÔ˘ Schofield-HW (19-21). √È ÂÍÈÛÒÛÂÈ˜ ·˘Ù¤˜ ¤ÁÈÓ·Ó ·fi ÙÔÓ Schofield ÁÈ· ÙÔÓ ˘ÔÏÔÁÈÛÌfi ÙˆÓ ÂÓÂÚÁÂÈ·ÎÒÓ ·Ó·ÁÎÒÓ ÛÂ ˘ÁÈ‹ ¿ÙÔÌ·, ÛÂ Ê˘ÛÈÔÏÔÁÈÎfi ÂÚÈ‚¿ÏÏÔÓ Î·È ÌÂ Î·Ï‹ Ê˘ÛÈÎ‹ Î·Ù¿ÛÙ·ÛË Î·È ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 1. ∏ ÚÔ‚ÏÂfiÌÂÓË Â› ÙÔÈ˜ ÂÎ·Ùfi ∫∂∏ ÔÚ›˙ÂÙ·È ·fi ÙË Û¯¤ÛË: ∫∂∏% = [ªÂÙÚÔ‡ÌÂÓË ∫∂∏/¶ÚÔ‚ÏÂfiÌÂÓË ∫∂∏] x 100. ∞fi ÙËÓ ·Ú·¿Óˆ Û¯¤ÛË ‰È·ÈÛÙÒÓÂÙ·È fiÙÈ fiÙ·Ó Ë ÙÈÌ‹ ÙË˜ ∫∂∏, Ë ÔÔ›· ÌÂÙÚ¿Ù·È ÛÙÔ ÂÚÁ·ÛÙ‹ÚÈÔ ÏËÛÈ¿˙ÂÈ ·˘Ù‹ ÙË˜ ÚÔ‚ÏÂfiÌÂÓË˜ ·fi ÙÈ˜ ÂÍÈÛÒÛÂÈ˜ Schofield-HW, ÙfiÙÂ Ë ÚÔ‚ÏÂfiÌÂÓË Â› ÙÔÈ˜ ÂÎ·Ùfi ∫∂∏ (∫∂∏%) ÏËÛÈ¿˙ÂÈ ÙÔ 100%. ∞ÓıÚˆÔÌÂÙÚÈÎ¿ ‰Â‰ÔÌ¤Ó· ∏ Ì¤ÙÚËÛË ÙÔ˘ ‡„Ô˘˜ (±0,1 cm) ¤ÁÈÓÂ ÌÂ ÙË ¯Ú‹ÛË ·Ó·ÛÙËÌfiÌÂÙÚÔ˘ SECA, ÂÓÒ Ë Ì¤ÙÚËÛË ÙÔ˘ ‚¿ÚÔ˘˜ (±0,1 kg) ÌÂ ÙË ¯Ú‹ÛË ËÏÂÎÙÚÔÓÈÎ‹˜ ˙˘Á·ÚÈ¿˜ Â‰¿ÊÔ˘˜ (SECA model 713 max 130 kg, min 2 kg) ÌÂ ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÔÏ‡ ÂÏ·ÊÚ¿ ÓÙ˘Ì¤ÓÔ˘˜. ŸÏÂ˜ ÔÈ ÌÂÙÚ‹ÛÂÈ˜ ¤ÁÈÓ·Ó ·ÎÔÏÔ˘ıÒÓÙ·˜ ÙÈ˜ ÎÏ·ÛÈÎ¤˜ ÙÂ¯ÓÈÎ¤˜ Î·È Â·Ó·Ï‹ÊıËÎ·Ó ‰Â‡ÙÂÚË ÊÔÚ¿ ÁÈ· ÂÈ‚Â‚·›ˆÛË (22,23). √ ‰Â›ÎÙË˜ Ì¿˙·˜ ÛÒÌ·ÙÔ˜ (¢ª™) ˘ÔÏÔÁ›˙ÂÙ·È ˆ˜ ÙÔ ËÏ›ÎÔ ÙÔ˘ ‚¿ÚÔ˘˜ ÛÒÌ·ÙÔ˜ (kg) ÚÔ˜ ÙÔ ‡„Ô˜ (m) ÛÙÔ ÙÂÙÚ¿ÁˆÓÔ.

∂ÎÙ›ÌËÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙË˜ ÎÏÈÓÈÎ‹˜ Î·Ù¿ÛÙ·ÛË˜ √È ‰ÔÎÈÌ·Û›Â˜ ÙË˜ ·Ó·ÓÂ˘ÛÙÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ ¤ÁÈÓ·Ó ÛÂ ·ÓÔÈÎÙfi Î‡ÎÏˆÌ· ÛÈÚÔÌ¤ÙÚËÛË˜ (JAEGER EOS-Sprint Oxygen Analyzer, Würzburg, Germany). ¶ÚÈÓ ·fi ÙË Ì¤ÙÚËÛË ÁÈÓfiÙ·Ó Â›‰ÂÈÍË ÙË˜ ‰È·‰ÈÎ·Û›·˜ Ì¤ÙÚËÛË˜ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ‰ÔÎÈÌ·ÛÙÈÎ¤˜ ÚÔÛ¿ıÂÈÂ˜ ·fi ÙÔ˘˜ ·ÛıÂÓÂ›˜, Ì¤¯ÚÈ ÙËÓ ÈÎ·ÓÔÔÈËÙÈÎ‹ ÂÍÔÈÎÂ›ˆÛ‹ ÙÔ˘˜ ÌÂ ÙË ‰È·‰ÈÎ·Û›·. ªÂ ÙÔÓ ÙÚfiÔ ·˘Ùfi ÌÂÙÚ‹ıËÎÂ Ô ‚›·È· ÂÎÓÂfiÌÂÓÔ˜ fiÁÎÔ˜ ·¤Ú· ÛÂ ¤Ó· ‰Â˘ÙÂÚfiÏÂÙÔ (FEV1), Ë ‰˘Ó·ÌÈÎ‹ ˙ˆÙÈÎ‹ ¯ˆÚËÙÈÎfiÙËÙ· (FVC) Î·È Ë Ì¤ÁÈÛÙË ÂÎÓÂ˘ÛÙÈÎ‹ ÚÔ‹ (PEFR) Î·È ÂÎÊÚ¿ÛÙËÎ·Ó ˆ˜ ÔÛÔÛÙfi ÙÔ˘ ÚÔ‚ÏÂfiÌÂÓÔ˘ ÁÈ· ÙÔ ·ÓÙ›ÛÙÔÈ¯Ô ‡„Ô˜ Î·È Ê‡ÏÔ. ∏ ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË ÚÔÛ‰ÈÔÚ›ÛÙËÎÂ ÌÂ ¤ÏÂÁ¯Ô ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÏÂ˘ÎÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ Î·È ÙË˜ C-·ÓÙÈ‰ÚÒÛ·˜ ÚˆÙÂ˝ÓË˜, Ù· ÔÔ›· ÌÂÙÚ‹ıËÎ·Ó ÌÂ ÙÈ˜ ÎÏ·ÛÈÎ¤˜ ÙÂ¯ÓÈÎ¤˜, Ì›· ËÌ¤Ú· ÚÈÓ ÙË Ì¤ÙÚËÛË ÙË˜ ∫∂∏. ∆·˘Ùfi¯ÚÔÓ· ¤ÁÈÓÂ Î·È Ë ·ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·Î·, Ë ÔÔ›· ·ÍÈÔÏÔÁ‹ıËÎÂ Î·Ù¿ Brasfield (24). √È Î·ÏÏÈ¤ÚÁÂÈÂ˜ Ù˘¤ÏˆÓ ÂÏ‹ÊıËÛ·Ó ÙËÓ ËÌ¤Ú· ÙË˜ ‰ÔÎÈÌ·Û›·˜. √ ÎÔÚÂÛÌfi˜ ÙÔ˘ ÔÍ˘ÁfiÓÔ˘ (SatO2) ÌÂÙÚ‹ıËÎÂ ÌÂ ·ÏÌÈÎfi ÔÍ‡ÌÂÙÚÔ (BCI International Waukes, HA Wisconcin Model 71000A1 Cat No 3301) ÛÙËÓ ·Ú¯‹ ÙË˜ ‰ÔÎÈÌ·Û›·˜. √ ‰Â›ÎÙË˜ ÎÏÈÓÈÎ‹˜ Î·Ù¿ÛÙ·ÛË˜ Î·ıÔÚ›ÛÙËÎÂ Û‡ÌÊˆÓ· ÌÂ Ù· ÎÚÈÙ‹ÚÈ· ÙˆÓ Shwachman-Kulczycki (25), ·fi ÙÔÓ ›‰ÈÔ ÂÍÂÙ·ÛÙ‹ ÁÈ· fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓÂ›˜. ™Ù·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË ∏ ÛÙ·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ¤ÁÈÓÂ ÌÂ ÙË ¯Ú‹ÛË ÙÔ˘ ÂÍÂÈ‰ÈÎÂ˘Ì¤ÓÔ˘ ÛÙ·ÙÈÛÙÈÎÔ‡ ·Î¤ÙÔ˘ SPSS v.11.0. ∆· ·ÔÙÂÏ¤ÛÌ·Ù· ÂÎÊÚ¿ÛÙËÎ·Ó ˆ˜ Ì¤ÛË ÙÈÌ‹ ± Ù˘ÈÎfi ÛÊ¿ÏÌ·. ∆· ‰Â‰ÔÌ¤Ó· ÙË˜ ∫∂∏ ·fi ÙÈ˜ ÌÂÙÚ‹ÛÂÈ˜ Û˘ÁÎÚ›ıËÎ·Ó ÌÂ ·ÓÙ›ÛÙÔÈ¯Â˜ ÙÈÌ¤˜ ÚÔ‚ÏÂfiÌÂÓË˜ ∫∂∏ ·fi ÙÈ˜ ÂÍÈÛÒÛÂÈ˜ ÙÔ˘ Schofield-HW, ÛÙÔ Ï·›ÛÈÔ ÙÔ˘ ‰›ÏÂ˘ÚÔ˘ ÂÏ¤Á¯Ô˘ ÙË˜ Î·Ù·ÓÔÌ‹˜ Student’s t test (two-tailed paired Student’s t-test). ∏ ÚÔ‚ÏÂfiÌÂÓË Â› ÙÔÈ˜ ÂÎ·Ùfi ∫∂∏ (KEH%) Û˘ÁÎÚ›ıËÎÂ ÌÂ ÙËÓ ÙÈÌ‹ ÙÔ˘ 100%, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ Î·È ¿ÏÈ ÙÔ t student’s test (‰›ÏÂ˘ÚÔ˜ ¤ÏÂÁ¯Ô˜ ÙË˜ Î·Ù·ÓÔÌ‹˜). √È Û˘Û¯ÂÙ›ÛÂÈ˜ ÌÂÙ·Í‡ ÙˆÓ ∫∂∏, ∫∂∏% Î·È FEV1%, FVC%, PEFR%, SatO2% Î·È ÎÏÈÓÈÎÔ‡ ‰Â›ÎÙË Shwachman ÌÂÏÂÙ‹ıËÎ·Ó ÛÙÔ Ï·›ÛÈÔ ÙË˜ ıÂˆÚ›·˜ ÙË˜ ·ÏÈÓ‰ÚfiÌËÛË˜ (Linear regression analysis). √ Û¯ÂÙÈÎfi˜ Û˘ÓÙÂÏÂÛÙ‹˜ Û˘Û¯¤ÙÈÛË˜ Pearson ˘ÔÏÔÁ›ÛÙËÎÂ ÁÈ· ÙËÓ ÂÚ·ÈÙ¤Úˆ ·Ó¿Ï˘ÛË ÙË˜ Û˘Û¯¤ÙÈÛË˜ ÌÂÙ·Í‡ ÙË˜ Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜ Î·È ÙˆÓ ·Ú·¿Óˆ ÎÏÈÓÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ. ∆Ô Â›Â‰Ô ·ÍÈÔÈÛÙ›·˜ ÛÙË ÛÙ·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË ÔÚ›ÛÙËÎÂ ÌÂ ÙÈÌ¤˜ p <0,05 ÙÔ˘Ï¿¯ÈÛÙÔÓ.

¶›Ó·Î·˜ 1. ∂ÍÈÛÒÛÂÈ˜ Schofield-HW ÁÈ· ÙÔÓ ˘ÔÏÔÁÈÛÌﬁ ÙË˜ ∫∂∏ (Kcal/ËÌ¤Ú·) ·ﬁ ÙÔ ‡„Ô˜ (height-H) Î·È ÙÔ ‚¿ÚÔ˜ (weight-W) ÛÂ ¿ÚÚÂÓÂ˜ Î·È ı‹ÏÂÈ˜ ∏ÏÈÎ›· (¤ÙË) <3 3-10 10-18 >18 ¶·È‰È·ÙÚÈÎ‹ 2006;69:440-446

ÕÚÚÂÓÂ˜

£‹ÏÂÈ˜

0,167W + 1517,4H - 617,6 19,59W + 130,3H + 414,9 16,25W + 137,2H + 515,5 15,057W + 10,04H + 705,8

16,252W + 1023,2H - 413,5 16,969W + 161,8H + 371,2 8,365W + 465,0H + 200,0 13,623W + 283,0H + 98,2

443

∫·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜ ÛÙËÓ Î˘ÛÙÈÎ‹ ›ÓˆÛË

∞ÔÙÂÏ¤ÛÌ·Ù· ∆· ·ÓıÚˆÔÌÂÙÚÈÎ¿ ‰Â‰ÔÌ¤Ó· Î·È Ù· ‰Â‰ÔÌ¤Ó· ÁÈ· ÙËÓ ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÛıÂÓÒÓ ÌÂ ∫π Î·Ù·ÁÚ¿ÊÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 2. H KEH ÛÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π ‚Ú¤ıËÎÂ ÌÂÁ·Ï‡ÙÂÚË ·fi ÙÈ˜ ÚÔ‚ÏÂfiÌÂÓÂ˜ ÙÈÌ¤˜ ÌÂ ‚¿ÛË ÙÈ˜ ÂÍÈÛÒÛÂÈ˜ Schofield-HW, 1626±49 Û˘ÁÎÚÈÓfiÌÂÓË ÌÂ 1472±72 (t=4,54, p<0,0001). ∏ ∫∂∏% ·ÓÙÈÛÙÔÈ¯Â› ÛÙÔ 110,96±2,35% (p<0,001) ÙË˜ ÚÔ‚ÏÂfiÌÂÓË˜ Î·È ¿ÏÈ ÌÂ ‚¿ÛË ÙÈ˜ ÂÍÈÛÒÛÂÈ˜ Schofield-HW. √ Ì¤ÛÔ˜ fiÚÔ˜ ÁÈ· ÙËÓ ∫∂∏ ÛÙ· ·ÁfiÚÈ· Î·È ÛÙ· ÎÔÚ›ÙÛÈ· ‚Ú¤ıËÎÂ 1778,7±72,9 Î·È 1473,19±43,41, ·ÓÙ›ÛÙÔÈ¯·. ∞˘Ùfi ·ÓÙÈÛÙÔÈ¯Â› ÛÂ ∫∂∏% 109,36±3,08% (p<0,007) Î·È 112,56±3,6 % (p<0,003), ·ÓÙ›ÛÙÔÈ¯· (¶›Ó·Î·˜ 3). ∞Ó Î·È Ô Ì¤ÛÔ˜ fiÚÔ˜ ÙË˜ ∫∂∏% ‹Ù·Ó ·˘ÍËÌ¤ÓÔ˜ ÛÂ Û¯¤ÛË ÌÂ ÙÈ˜ ÚÔ‚ÏÂfiÌÂÓÂ˜ ÙÈÌ¤˜ Î·È ÛÙ· ‰‡Ô Ê‡Ï·, ˆÛÙfiÛÔ ·˘Ùfi˜ ÛÙ· ÎÔÚ›ÙÛÈ· ‹Ù·Ó ·ÎfiÌË ÈÔ ·˘ÍËÌ¤ÓÔ˜ ÛÂ Û¯¤ÛË ÌÂ Ù· ·ÁfiÚÈ·. ∏ ÁÚ·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ¤‰ÂÈÍÂ fiÙÈ ˘¿Ú¯ÂÈ ·ÚÓËÙÈÎ‹ Û˘Û¯¤ÙÈÛË ÙË˜ ∫∂∏% ÌÂ ÙÔÓ ÎÏÈÓÈÎfi ‰Â›ÎÙË Shwachman, FEV1%, FVC% Î·È PEFR%. ¢ÂÓ ‚Ú¤ıËÎÂ Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ ÙÔ˘ ÎÔÚÂÛÌÔ‡ ÔÍ˘ÁfiÓÔ˘ (SatO2) Î·È ÙË˜ ∫∂∏%. ™˘ÁÎÂÎÚÈÌ¤Ó·, ‚Ú¤ıËÎÂ ÛËÌ·ÓÙÈÎ‹ Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ ÙÔ˘ ÎÏÈÓÈÎÔ‡ ‰Â›ÎÙË Shwachman Î·È ∫∂∏%, ¯ˆÚ›˜ ÛÙ·ÙÈÛÙÈÎ¿ ÛËÌ·ÓÙÈÎ‹ ‰È·ÊÔÚ¿ ·Ó¿ÌÂÛ· ÛÙ· ‰‡Ô Ê‡Ï·. ∏ ÁÚ·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË ·Ó¿ÌÂÛ· ÛÙÔÓ ‰Â›ÎÙË Shwachman Î·È ÛÙËÓ ∫∂∏% ÂÎÊÚ¿˙ÂÙ·È ÌÂ ÙÔÓ ¶›Ó·Î·˜ 2. ∞ÓıÚˆÔÌÂÙÚÈÎ¿ ÛÙÔÈ¯Â›· Î·È ‰Â‰ÔÌ¤Ó· ·fi ÙËÓ ·Ó·ÓÂ˘ÛÙÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· ·ÛıÂÓÒÓ ÌÂ ∫π ∏ÏÈÎ›· µ¿ÚÔ˜ ¢ª™ FEV1% FVC%

™˘ÓÔÏÈÎ¿

ÕÚÚÂÓÂ˜

£‹ÏÂÈ˜

19,72±1,0 54,2±2,2 20,5±0,63 76,39±4,49 79,96±4,0

19,25±1,37 57,1±3,35 20,4±0,9 73,31±6,51 77,58±6,0

20,21±1,46 51,87±2,77 20,4±0,6 79,47±6,26 88,34±5,46

Û˘ÓÙÂÏÂÛÙ‹ Pearson Î·È Ê·›ÓÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 1 (r=-0,654, p<0,0001 fiÏÔÈ ÔÈ ·ÛıÂÓÂ›˜, r=-0,681 Î·È r=-0,662 ·ÁfiÚÈ· Î·È ÎÔÚ›ÙÛÈ·, ·ÓÙ›ÛÙÔÈ¯·). ∂›Ó·È Ê·ÓÂÚfi fiÙÈ Î·ıÒ˜ Ô ÎÏÈÓÈÎfi˜ ‰Â›ÎÙË˜ ÂÏ·ÙÙÒÓÂÙ·È, Ë ∫∂∏% ·˘Í¿ÓÂÙ·È. ∏ ÁÚ·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ FEV1% Î·È ∫∂∏% Ê·›ÓÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 2 (r=-0,475, p<0,003 fiÏÔÈ ÔÈ ·ÛıÂÓÂ›˜, r=-0,484 Î·È r=-0,510 ·ÁfiÚÈ· Î·È ÎÔÚ›ÙÛÈ·, ·ÓÙ›ÛÙÔÈ¯·). ∏ Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ ÙˆÓ FVC% Î·È ∫∂∏% Ê·›ÓÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 3 (r=-0,570, p<0,0001 fiÏÔÈ ÔÈ ·ÛıÂÓÂ›˜, r=-0,570 Î·È r=-0,610 ·ÁfiÚÈ· Î·È ÎÔÚ›ÙÛÈ·, ·ÓÙ›ÛÙÔÈ¯·). ∂›Ó·È Û·Ê¤˜ fiÙÈ ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈÎ‹ ·ÚÓËÙÈÎ‹ ÁÚ·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË ·Ó¿ÌÂÛ· ÛÙËÓ ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· Î·È ÛÙËÓ ∫∂∏%. ∆¤ÏÔ˜, Ë Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ PEFR% Î·È ∫∂∏% ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 4 (r=-0,39, p<0,016 fiÏÔÈ ÔÈ ·ÛıÂÓÂ›˜, r=-0,440 Î·È r=-0,310 ·ÁfiÚÈ· Î·È ÎÔÚ›ÙÛÈ·, ·ÓÙ›ÛÙÔÈ¯·).

™˘˙‹ÙËÛË ™Â fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÙË˜ ·ÚÔ‡Û·˜ ÌÂÏ¤ÙË˜ ÌÂ ∫π, Ô ¢ª™ ‹Ù·Ó >18,5. ∞˘Ùfi ‰Â›¯ÓÂÈ Î·Ï‹ Î·Ù¿ÛÙ·ÛË ıÚ¤„Ë˜, ·Ú¿ ÙËÓ ·ÁÎÚÂ·ÙÈÎ‹ ·ÓÂ¿ÚÎÂÈ·, Ë ÔÔ›· ¯·Ú·ÎÙ‹ÚÈ˙Â ÙËÓ ÏÂÈÔ„ËÊ›· ÙˆÓ ·ÛıÂÓÒÓ ÙË˜ ÌÂÏ¤ÙË˜. ∏ Î·Ù¿ÏÏËÏË ·ÓÙÈÌÂÙÒÈÛË ÛÂ Û˘Ó‰˘·ÛÌfi ÌÂ ‰È·ÈÙËÙÈÎ‹ ˘ÔÛÙ‹ÚÈÍË ÂÍËÁÔ‡Ó ÙÔÓ Ê˘ÛÈÔÏÔÁÈÎfi ¢ª™. ∞fi ÙÈ˜ Ì¤ÛÂ˜ ÙÈÌ¤˜ ÙˆÓ FEV1% Î·È FVC% Û˘ÌÂÚ·›ÓÂÙ·È fiÙÈ Ë ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó Ì¤ÙÚÈ· ÂËÚÂ·ÛÌ¤ÓË. ∏ Ì¤ÛË ÙÈÌ‹ ÙÔ˘ FEV1% Î·È ÙË˜ FVC% ÛÙ· ÎÔÚ›ÙÛÈ· ‚Ú¤ıËÎÂ ÂÏ·ÊÚ¿ ˘„ËÏfiÙÂÚË ·fi fi,ÙÈ ÛÙ· ·ÁfiÚÈ·. ∏ ÛÙ·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ¤‰ÂÈÍÂ fiÙÈ Ë ‰È·ÊÔÚ¿ ·˘Ù‹ ‰ÂÓ ‹Ù·Ó ÛÙ·ÙÈÛÙÈÎ¿ ÛËÌ·ÓÙÈÎ‹. ªÂ ÎÚÈÙ‹ÚÈÔ ÙË Ì¤ÛË ÙÈÌ‹ ÙÔ˘ ‰Â›ÎÙË Shwachman, ÔÈ ·ÛıÂÓÂ›˜ Î·Ù¿ Ì¤ÛÔÓ fiÚÔ ‚Ú›ÛÎÔÓÙ·Ó ÛÂ Î·Ï‹ ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË (25). ™ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ∫π Î·È ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ Ì¤ÙÚÈ·˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È Î·Ï‹˜ ÎÏÈÓÈÎ‹˜ Î·Ù¿ÛÙ·ÛË˜ ¯ˆÚ›˜ ÚfiÛÊ·ÙË ÏÔ›ÌˆÍË,

¶›Ó·Î·˜ 3. ∏ ÌÂÙÚÔ‡ÌÂÓË Î·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜ (∫∂∏), Ë ÚÔ‚ÏÂfiÌÂÓË ∫∂∏ ·fi ÙÈ˜ ÂÍÈÛÒÛÂÈ˜ Schofield-HW Î·È ∫∂∏% ˆ˜ ÔÛÔÛÙfi ÙË˜ ÚÔ‚ÏÂfiÌÂÓË˜ ·fi ÙÈ˜ ÂÍÈÛÒÛÂÈ˜ Schofield-HW. ∆ÈÌ¤˜ p Î·È t ·fi ·Ó¿Ï˘ÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ, ÌÂ ÙË ¯Ú‹ÛË ÙÔ˘ ‰›ÏÂ˘ÚÔ˘ ÂÏ¤Á¯Ô˘ ÙË˜ Î·Ù·ÓÔÌ‹˜ Student t test. ªÂÙÚÔ‡ÌÂÓË ∫∂∏ (Kcal/ËÌ¤Ú·) ™˘ÓÔÏÈÎ¿ ÕÚÚÂÓÂ˜ £‹ÏÂÈ˜

1625,95±48,8 1778,7±72,9 1473,19±43,41

Schofield-HW

ªÂÙÚÔ‡ÌÂÓË ∫∂∏ ÛÂ Û¯¤ÛË ÌÂ Schofield t p

1472,36±39,56 1626,94±51,78 1317,79±33,15

4,54 3,008 3,35

0,0001 0,008 0,004

∫∂∏%

∫∂∏% vs 100% t

110,96±2,35 109,36±3,08 112,56±3,6

4,658 0,0001 3,037 0,007 3,489 0,003

∞ÔÙÂÏ¤ÛÌ·Ù· ÂÎÊÚ·ÛÌ¤Ó· ˆ˜ Ì¤ÛË ÙÈÌ‹ ± Ù˘ÈÎﬁ ÛÊ¿ÏÌ· ¶·È‰È·ÙÚÈÎ‹ 2006;69:440-446

444

∆. ªÔ‡‰ÈÔ˘ Î·È Û˘Ó.

160 140 120

Shwachman

100 95 90 85 80 75 70 65 60 70

FVC%

100

100 110 KEH%

40 120

130

140

0 70

∂ÈÎfiÓ· 1. °Ú·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË ÎÏÈÓÈÎÔ‡ ‰Â›ÎÙË Shwachman fiÏˆÓ ÙˆÓ ·ÛıÂÓÒÓ ÌÂ ÙËÓ ∫∂∏%. ŸÛÔ ÂÏ·ÙÙÒÓÂÙ·È Ô ‰Â›ÎÙË˜ Shwachman, ÙfiÛÔ ·˘Í¿ÓÂÙ·È Ë ∫∂∏%.

Ë KEH ‚Ú¤ıËÎÂ ·˘ÍËÌ¤ÓË. ∞˘Ùfi Û˘ÌÊˆÓÂ› ÌÂ ÙË ‚È‚ÏÈÔÁÚ·Ê›· (10,11). ™Ù· ·ÁfiÚÈ·, Ë ∫∂∏ ‹Ù·Ó ˘„ËÏfiÙÂÚË ·fi fi,ÙÈ ÛÙ· ÎÔÚ›ÙÛÈ·, fiˆ˜ ·Ó·ÌÂÓfiÙ·Ó (6,26). ∏ ‰È·ÊÔÚ¿ ·Ô‰fiıËÎÂ ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ¿ÏÈË˜ Ì¿˙·˜ ÛÙ· ·ÁfiÚÈ· ÛÂ Û¯¤ÛË ÌÂ Ù· ÎÔÚ›ÙÛÈ· (6,27-29). ™ÙÔ˘˜ ›‰ÈÔ˘˜ ·ÛıÂÓÂ›˜, Ë ÚÔ‚ÏÂfiÌÂÓË ∫∂∏% ‹Ù·Ó Â›ÛË˜ ·˘ÍËÌ¤ÓË Î·È ÛÙ· ‰‡Ô Ê‡Ï·, ·ÏÏ¿ ÛÂ ·ÓÙ›ıÂÛË ÌÂ ÙË ÌÂÙÚÔ‡ÌÂÓË ÙÈÌ‹ ÙË˜ ∫∂∏, Ë ∫∂∏% ÛÙ· ÎÔÚ›ÙÛÈ· ‚Ú¤ıËÎÂ ˘„ËÏfiÙÂÚË ·fi fi,ÙÈ ÛÙ· ·ÁfiÚÈ· (112% Î·È 109%, ·ÓÙ›ÛÙÔÈ¯·). ∏ ∫∂∏% ÔÚ›ÛÙËÎÂ ˆ˜ ÙÔ Â› ÙÔÈ˜ ÂÎ·Ùfi ÔÛÔÛÙfi ÙË˜ ÚÔ‚ÏÂfiÌÂÓË˜ ∫∂∏, Û˘ÁÎÚÈÓfiÌÂÓË ÌÂ ·ÓÙ›ÛÙÔÈ¯Â˜ ÙÈÌ¤˜ ˘ÁÈÒÓ ·ÙfiÌˆÓ ÌÂ Ù· ›‰È· ÛˆÌ·ÙÔÌÂÙÚÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ (26,30). ∏ ÌÂÙÚÔ‡ÌÂÓË ∫∂∏ ÂÍ·ÚÙ¿Ù·È ¤ÓÙÔÓ· ·fi Ù· ÛˆÌ·ÙÔÌÂÙÚÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿, ÂÓÒ ·ÓÙ›ıÂÙ· Ë ∫∂∏% ·ÓÙÈÚÔÛˆÂ‡ÂÈ ÙËÓ ·fiÎÏÈÛË ÙË˜ Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜ ÙÔ˘ ·ÛıÂÓ‹ ÛÂ Û¯¤ÛË ÌÂ ·˘Ù‹ Ô˘ ÚÔ‚Ï¤ÂÙ·È ÁÈ· ¤Ó· ·ÓÙ›ÛÙÔÈ¯Ô ˘ÁÈ¤˜ ¿ÙÔÌÔ. √È Û˘ÁÎÚ›ÛÂÈ˜ ‚·Û›ÛÙËÎ·Ó ÛÙÈ˜ ÂÍÈÛÒÛÂÈ˜ ÙÔ˘ Schofield-HW (30). ∆Ô Î·Ù·ÏÏËÏfiÙÂÚÔ Ì¤ÁÂıÔ˜ ÁÈ· ÙË Û˘Û¯¤ÙÈÛË ÙË˜ Î·Ù·Ó¿ÏˆÛË˜ ÂÓ¤ÚÁÂÈ·˜ ÛÙËÓ ËÚÂÌ›· ÌÂ ÙËÓ ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË ·ÛıÂ-

120

100

PEFR%

140

120 FEV1%

140

60 20 0 70

100 110 ∫∂∏%

0 70 130

140

∂ÈÎfiÓ· 2. °Ú·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË FEV1% fiÏˆÓ ÙˆÓ ·ÛıÂÓÒÓ ÌÂ ÙËÓ ∫∂∏%. ŸÛÔ ÂÏ·ÙÙÒÓÂÙ·È Ô FEV1%, ÙfiÛÔ ·˘Í¿ÓÂÙ·È Ë ∫∂∏%.

100 110 KEH%

120

130

140

60 20

120

80 40

y=-0,9061x+176,95 r=-0,475 p<0,003

ÓÒÓ ÌÂ ∫π Â›Ó·È Ë ∫∂∏% (30), ÂÓÒ Ë ÌÂÙÚÔ‡ÌÂÓË ∫∂∏ ‰›ÓÂÈ ÏËÚÔÊÔÚ›Â˜ ÁÈ· ÙÈ˜ ÂÓÂÚÁÂÈ·Î¤˜ ÙÔ˘˜ ·Ó¿ÁÎÂ˜. ¶ÂÚ·ÈÙ¤Úˆ ÛÙ·ÙÈÛÙÈÎ‹ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ÁÈ· ÙËÓ ∫∂∏% ¤‰ÂÈÍÂ fiÙÈ Ë ‰È·ÊÔÚ¿ ÙË˜ KEH% ·Ó¿ÌÂÛ· ÛÙ· ·ÁfiÚÈ· Î·È ÛÙ· ÎÔÚ›ÙÛÈ·, Ë ÔÔ›· ·Ó·Ê¤ÚıËÎÂ ·Ú·¿Óˆ, ‰ÂÓ Â›Ó·È ÛÙ·ÙÈÛÙÈÎ¿ ÛËÌ·ÓÙÈÎ‹. ∞˘Ùfi Ê·›ÓÂÙ·È Ó· ¤Ú¯ÂÙ·È ÛÂ ·ÓÙ›ıÂÛË ÌÂ Ù· Â˘Ú‹Ì·Ù· ÙˆÓ Allen Î·È Û˘Ó (26), ÔÈ ÔÔ›ÔÈ ‚Ú‹Î·Ó ‰È·ÊÔÚ¿ ·Ó¿ÌÂÛ· ÛÙ· ‰‡Ô Ê‡Ï·, ·ÎÔÏÔ˘ıÒÓÙ·˜ fiÌˆ˜, ‰È·ÊÔÚÂÙÈÎ‹ ÌÂıÔ‰ÔÏÔÁ›·. ∏ Û˘Û¯¤ÙÈÛË ÙË˜ ∫∂∏% ÌÂ ÙËÓ ÓÂ˘ÌÔÓÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· ‰Â›¯ÓÂÈ ÌÈ· ÛËÌ·ÓÙÈÎ‹ ·ÚÓËÙÈÎ‹ ÁÚ·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ ∫∂∏% Î·È FEV1%, FVC%. ∞ÓÙ›ıÂÙ·, Ë ÌÂÙÚÔ‡ÌÂÓË ∫∂∏ ¤¯ÂÈ ÛÙ·ÙÈÛÙÈÎ¿ ÛËÌ·ÓÙÈÎ‹ Û˘Û¯¤ÙÈÛË ÌÂ FEV1% Î·È FVC% ÌfiÓÔ ÛÙ· ·ÁfiÚÈ·. øÛÙfiÛÔ, fiˆ˜ ¤¯ÂÈ ·Ó·ÊÂÚıÂ›, Ë ¯Ú‹ÛË ÙË˜ ∫∂∏ ·ÓÙ› ÙË˜ ∫∂∏% ÌÔÚÂ› Ó· Ô‰ËÁ‹ÛÂÈ ÛÂ Ï·Óı·ÛÌ¤Ó· Û˘ÌÂÚ¿ÛÌ·Ù·. πÛ¯˘Ú‹ Û˘Û¯¤ÙÈÛË ‚Ú¤ıËÎÂ ÌÂÙ·Í‡ ÙË˜ ∫∂∏% Î·È ÙÔ˘ ÎÏÈÓÈÎÔ‡ ‰Â›ÎÙË Shwachman. 160

y=-0,9782x+188,51 r=-0,57 p<0,0001

∂ÈÎfiÓ· 3. °Ú·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË FVC% fiÏˆÓ ÙˆÓ ·ÛıÂÓÒÓ ÌÂ ÙËÓ ∫∂∏%. ŸÛÔ ÂÏ·ÙÙÒÓÂÙ·È Ë FVC%, ÙfiÛÔ ·˘Í¿ÓÂÙ·È Ë ∫∂∏%.

160

¶·È‰È·ÙÚÈÎ‹ 2006;69:440-446

80 60

y=-0,3288x+123,48 r=-0,654 p<0,0001

y=-0,6376x+160,69 r=0,39 80

100 110 ∫∂∏%

120

130

140

∂ÈÎfiÓ· 4. °Ú·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË PEFR% fiÏˆÓ ÙˆÓ ·ÛıÂÓÒÓ ÌÂ ÙËÓ ∫∂∏%. ŸÛÔ ÂÏ·ÙÙÒÓÂÙ·È o PEFR%, ÙfiÛÔ ·˘Í¿ÓÂÙ·È Ë ∫∂∏%.

445

∫·Ù·Ó¿ÏˆÛË ÂÓ¤ÚÁÂÈ·˜ ËÚÂÌ›·˜ ÛÙËÓ Î˘ÛÙÈÎ‹ ›ÓˆÛË

∫·ıÒ˜ Ô ‰Â›ÎÙË˜ Shwachman ÂÏ·ÙÙÒÓÂÙ·È, ‰ËÏ·‰‹ ÂÈ‚·Ú‡ÓÂÙ·È Ë ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË ÙÔ˘ ·ÛıÂÓ‹, Ë ∫∂∏% ·˘Í¿ÓÂÙ·È (·ÚÓËÙÈÎ‹ ÁÚ·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË). √ ‰Â›ÎÙË˜ Shwachman ¤¯ÂÈ ¯ÚËÛÈÌÔÔÈËıÂ› ˆ˜ ¤Ó‰ÂÈÍË ÙË˜ ‚·Ú‡ÙËÙ·˜ ÙË˜ ÓfiÛÔ˘ ÙË˜ ∫π (30). øÛÙfiÛÔ, Ô ‰Â›ÎÙË˜ Shwachman Â›Ó·È ¤Ó·˜ ˘ÔÎÂÈÌÂÓÈÎfi˜ ‰Â›ÎÙË˜ Î·È Ú¤ÂÈ ¿ÓÙ· Ó· ˘ÔÏÔÁ›˙ÂÙ·È ·fi ÙÔÓ ›‰ÈÔ ÂÍÂÙ·ÛÙ‹, Î¿ÙÈ Ô˘ fiÌˆ˜ ‰ÂÓ Â›Ó·È ¿ÓÙ· ÂÊÈÎÙfi ÛÙËÓ ÎÏÈÓÈÎ‹ Ú¿ÍË. ∫·ıÒ˜ ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈÎ‹ ÁÚ·ÌÌÈÎ‹ Û˘Û¯¤ÙÈÛË ÌÂÙ·Í‡ ÙË˜ ∫∂∏% Î·È ÙÔ˘ ‰Â›ÎÙË Shwachman, fiˆ˜ Î·È ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÏÂÈÙÔ˘ÚÁ›·˜, ÚÔÙÂ›ÓÂÙ·È Ë ∫∂∏% ˆ˜ ¤Ó·˜ ·ÓÙÈÎÂÈÌÂÓÈÎfi˜ ‰Â›ÎÙË˜ ÂÎÙ›ÌËÛË˜ ‚·Ú‡ÙËÙ·˜ ÙË˜ ÓfiÛÔ˘ ÙË˜ ∫π. ∂ÈÏ¤ÔÓ, Ë ∫∂∏% Ì¿˜ ‰›ÓÂÈ ÏËÚÔÊÔÚ›Â˜ Û¯ÂÙÈÎ¿ ÌÂ ÙÈ˜ ÂÓÂÚÁÂÈ·Î¤˜ ·Ó¿ÁÎÂ˜ ÙÔ˘ ·ÛıÂÓ‹ Î·È ÌÔÚÂ› Ó· Â›Ó·È ¯Ú‹ÛÈÌË ÛÙËÓ ¤ÁÎ·ÈÚË ÚÔÛ·ÚÌÔÁ‹ ÙË˜ ‰›·ÈÙ¿˜ ÙÔ˘. ™˘ÌÂÚ·›ÓÂÙ·È fiÙÈ Ë ¯Ú‹ÛË ÙË˜ ∫∂∏% Â›Ó·È ·Ó·ÁÎ·›· ÛÙËÓ ÎÏÈÓÈÎ‹ Ú¿ÍË ˆ˜ ‰Â›ÎÙË˜ ÙˆÓ ÂÓÂÚÁÂÈ·ÎÒÓ ·Ó·ÁÎÒÓ Î·È ÙË˜ ‚·Ú‡ÙËÙ·˜ ÙË˜ ÓfiÛÔ˘ ·ÛıÂÓÒÓ ÌÂ ∫π Î·Ù¿ ÙËÓ ÂÙ‹ÛÈ· ÂÎÙ›ÌËÛË ÙË˜ Î·Ù¿ÛÙ·Û‹˜ ÙÔ˘.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Soutter VL, Kristidis P, Gruca MA, Gaskin KJ. Chronic undernutrition/growth retardation in cystic fibrosis. Clin Gastroenterol 1986;15:137-155. 2. Cystic Fibrosis Patient Registry. Annual Data Report 1998. Cystic Fibrosis Foundation. Bethesda, Maryland, USA; 1999. 3. McCloskey M, Redmond AO, Pyper S, McCabe C, Westerterp KR, Elborn JS. Total energy expenditure in stable patients with cystic fibrosis. Clin Nutr 2001;20:235-241. 4. Marin VB, Velandia S, Hunter B, Gattas V, Fielbaum O, Herrera O et al. Energy expenditure, nutrition status, and body composition in children with cystic fibrosis. Nutrition 2004;20:181-186. 5. Mc Closkey M, Redmond AO, Mc Cabe C, Pyper S, Westerterp KR, Elborn SJ. Energy balance in cystic fibrosis when stable and during a respiratory exacerbation. Clin Nutr 2004;23:1405-1412. 6. Goran MI, Kaskoun M, Johnson R. Determinants of resting energy expenditure in young children. J Pediatr 1994;125:362-367. 7. Steinkamp G, Drommer A, von der Hardt H. Resting energy expenditure before and after treatment for Pseudomonas aeruginosa infection in patients with cystic fibrosis. Am J Clin Nutr 1993;57:685-689. 8. Beghin L, Gottrand F, Michaud L, Loeuille GA,Wizla-Derambure N, Sardet A. Impact of intravenous antibiotic therapy on total daily energy expenditure and physical activity in cystic fibrosis children with Pseudomonas aeruginosa pulmonary exacerbation. Pediatr Res 2003;54:756-761.

9. Stallings VA, Fung EB, Hofley PM, Scanlin TF. Acute pulmonary exacerbation is not associated with increased energy expenditure in children with cystic fibrosis. J Pediatr 1998;132:493-499. 10. Zemel BS, Kawchak DA, Cnaan A, Zhao H, Scanlin TF, Stallings VA. Prospective evaluation of resting energy expenditure, nutritional status, pulmonary function, and genotype in children with cystic fibrosis. Pediatr Res 1996;40:578-586. 11. Vaisman N, Pencharz PB, Corey M, Canny GJ, Hahn E. Energy expenditure of patients with cystic fibrosis. J Pediatr 1987;111:496-500. 12. Tomezsko JL, Stallings VA, Kawchak DA, Goin JE, Diamond G, Scanlin TF. Energy expenditure and genotype of children with cystic fibrosis. Pediatr Res 1994;35:451-460. 13. Girardet JP, Tounian P, Sardet A, Veinberg F, Grimfeld A, Tournier G et al. Resting energy expenditure in infants with cystic fibrosis. J Pediatr Gastroenterol Nutr 1994;18:214-219. 14. Matarese LE. Indirect calorimetry: technical aspects. J Am Diet Assoc 1997;97 (Suppl 2):S154-S160. 15. Bell SC, Saunders MJ, Elborn JS, Shale DJ. Resting energy expenditure and oxygen cost of breathing in patients with cystic fibrosis. Thorax 1996;51:126-131. 16. Johnson MR, Ferkol TW, Shepherd RW. Energy cost of activity and exercise in children and adolescents with cystic fibrosis. J Cyst Fibros 2006;5:53-58. 17. Weir JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 1949;109:1-9. 18. AARC clinical practice guideline. Metabolic measurement using indirect calorimetry during mechanical ventilation. American Association for Respiratory Care. Respir Care 1994;39:1170-1175. 19. Schofield WN. Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr Clin Nutr 1985;39 (Suppl 1):S5-S41. 20. Rodriguez G, Moreno LA, Sarria A, Fleta J, Bueno M. Resting energy expenditure in children and adolescents: agreement between calorimetry and prediction equations. Clin Nutr 2002;21:255-260. 21. Kaplan AS, Zemel BS, Neiswender KM, Stallings VA. Resting energy expenditure in clinical pediatrics: measured versus prediction equations. J Pediatr 1995;127:200-205. 22. Gerver WJM, De Bruin R. Paediatric Morphometrics: A Reference Manual. Utrecht, The Netherlands: Wetenschappelijke Uitgeverij Bunge; 1996. 23. Cameron N. The methods of auxological anthropometry. In: Falkner F, Tanner JM, editors. Human growth: a comprehensive treatise. 2nd ed. Vol. 2. New York: Plenum Press; 1986. p. 3-46. 24. Brasfield D, Hicks G, Soong S, Tiller RE. The chest roentgenogram in cystic fibrosis: a new scoring system. Paediatrics 1979;63:24-29. 25. Shwachman ∏, Kulczycki LL. Long-term study of 105 patients with cystic fibrosis; studies made over a five- to fourteen-year period. AMA J Dis Child 1958; 96:6-15. 26. Allen JR, McCauley JC, Selby AM, Waters DL, Gruca MA, Baur LA et al. Differences in resting energy ¶·È‰È·ÙÚÈÎ‹ 2006;69:440-446

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expenditure between male and female children with cystic fibrosis. J Pediatr 2003;142:15-19. 27. Weinsier RL, Schutz Y, Bracco D. Reexamination of the relationship of resting metabolic rate to fat-free mass and to the metabolically active components of fat-free mass in humans. Am J Clin Nutr 1992;55: 790-794. 28. Ferraro R, Lillioja S, Fontvieille AM, Rising R, Bogardus C, Ravussin E. Lower sedentary metabolic rate

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in women compared with men. J Clin Invest 1992; 90:780-784. 29. Arciero PJ, Goran MI, Poehlman ET. Resting metabolic rate is lower in women than in men. J. Appl Physiol 1993;75:2514-2520. 30. Dorlochter L, Helgheim V, Roksund OD, Rosendahl K, Fluge G. Shwachman-Kulczycki score and resting energy expenditure in cystic fibrosis. J Cyst Fibros 2003;2:148-151.

∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏

CASE REPORT

447

°ÂÓÂÙÈÎfi˜ Î·È ÎÏÈÓÈÎÔÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÛÂ ÔÈÎÔÁ¤ÓÂÈ· ÌÂ ÎÏÈÓÈÎ‹ ÂÙÂÚÔÁ¤ÓÂÈ· Û˘Ó‰ÚfiÌÔ˘ Noonan ™. ∫›ÙÛÈÔ˘ - ∆˙¤ÏË, Õ. ¶··‰ÔÔ‡ÏÔ˘, ∞. •·˚‰¿Ú·, °. ¶··‰fiÔ˘ÏÔ˜, ∞.-ª. ª·ÁÈ¿ÎÔ˘, ∞. ∫ÔÏÈ·Ï¤ÍË, ∞. ª·‡ÚÔ˘, ∂. ∫·Ó·‚¿ÎË˜, ¶. ¡ÈÎÔÏ·˝‰Ô˘

¶ÂÚ›ÏË„Ë: ∆Ô Û‡Ó‰ÚÔÌÔ Noonan (NS) Â›Ó·È Û˘¯Ófi ÁÂÓÂÙÈÎfi ÓfiÛËÌ·. Ã·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ‚Ú·¯˘ÛˆÌ›·, ÎÚ·ÓÈÔÚÔÛˆÈÎ¤˜ ·ÓˆÌ·Ï›Â˜, Û˘ÁÁÂÓ‹ Î·Ú‰ÈÔ¿ıÂÈ·, ÎÚ˘„ÔÚ¯›·, ·ÓˆÌ·Ï›Â˜ ÙÔ˘ ıÒÚ·Î·, ÙÔ˘ ÛÎÂÏÂÙÔ‡ Î·È ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ, ·ÈÌÔÚÚ·ÁÈÎ‹ ‰È¿ıÂÛË Î·È ÓÔËÙÈÎ‹ ˘ÛÙ¤ÚËÛË. ∫ÏËÚÔÓÔÌÂ›Ù·È ÌÂ ·˘ÙÔÛˆÌ·ÙÈÎfi ÂÈÎÚ·ÙËÙÈÎfi ¯·Ú·ÎÙ‹Ú· Î·È ÂÌÊ·Ó›˙ÂÈ ÔÈÎ›ÏË ÎÏÈÓÈÎ‹ ¤ÎÊÚ·ÛË. ªÂÙ·ÏÏ¿ÍÂÈ˜ ÛÙÔ ˘Â‡ı˘ÓÔ ÁÔÓ›‰ÈÔ (ƒ∆ƒ¡ 11) ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙÔ 33-60% ÙˆÓ ·ÛıÂÓÒÓ ÌÂ Ê·ÈÓfiÙ˘Ô NS. ¶ÂÚÈÁÚ¿ÊÂÙ·È ÔÈÎÔÁ¤ÓÂÈ· ÌÂ Û‡Ó‰ÚÔÌÔ Noonan ÌÂ ÎÏÈÓÈÎ‹ ÂÙÂÚÔÁ¤ÓÂÈ· ÛÂ 3 ÁÂÓÈ¤˜ ·fi ÙË ÌËÙ¤Ú·. ∏ ÂÚ›ÙˆÛË ‰Â›ÎÙË˜, ÎÔÚ›ÙÛÈ 4 ÂÙÒÓ Î·È ÚÔ˚fiÓ ‰›‰˘ÌË˜ ÂÍˆÛˆÌ·ÙÈÎ‹˜ Î‡ËÛË˜, ¤¯ÂÈ ‚Ú·¯˘ÛˆÌ›· Î·È ‰ÈÔÚıˆıÂ›Û· ÛÙ¤ÓˆÛË ÓÂ˘ÌÔÓÈÎ‹˜. ∏ ÌËÙ¤Ú· Â›Ó·È Â›ÛË˜ ‚Ú·¯‡ÛˆÌË Î·È ¤¯ÂÈ ÈÛÙÔÚÈÎfi ·ÈÌÔÚÚ·ÁÈÎ‹˜ ‰È¿ıÂÛË˜ Î·È Î·ı˘ÛÙ¤ÚËÛË˜ ÂÌÌËÓ·Ú¯‹˜. √ ÌËÙÚÈÎfi˜ ıÂ›Ô˜ ¤¯ÂÈ Î·ÓÔÓÈÎfi ·Ó¿ÛÙËÌ· Î·È “Û˘ÛÙÔÏÈÎfi Ê‡ÛËÌ·”. ∏ ‰›‰˘ÌË ·‰ÂÏÊ‹ ÙË˜ ·ÛıÂÓÔ‡˜ Î·Ù¤ÏËÍÂ ÛÂ ËÏÈÎ›· 9 ÌËÓÒÓ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈÎ‹ ‰ÈfiÚıˆÛË ÛÙ¤ÓˆÛË˜ ÓÂ˘ÌÔÓÈÎ‹˜. ∏ ÁÈ·ÁÈ¿ ·fi ÙË ÌËÙ¤Ú· Î·Ù¤ÏËÍÂ ÛÂ ËÏÈÎ›· 30 ÂÙÒÓ ·fi Î·Ú‰È·Î‹ ÚÔÛ‚ÔÏ‹. ¶·Ú¿ ÙË ‰È·ÊÔÚÂÙÈÎ‹ ÚÔÛ‚ÔÏ‹ ÔÚÁ¿ÓˆÓ Î·È Û˘ÛÙËÌ¿ÙˆÓ fiÏ· Ù· ·ÓˆÙ¤Úˆ Ì¤ÏË ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ Â›¯·Ó ÎÔÈÓ¿ ÌÔÚÊÔÏÔÁÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ (ÙÚÈÁˆÓÈÎfi ÚfiÛˆÔ, ˘ÂÚÙÂÏÔÚÈÛÌfi, ·ÓÙÈÌÔÁÁÔÏÔÂÈ‰Â›˜ ‚ÏÂÊ·ÚÈÎ¤˜ Û¯ÈÛÌ¤˜, ÚÔ¤¯ÔÓÙÂ˜ ÔÊı·ÏÌÔ‡˜, Â›Î·ÓıÔ, ·ÔÂÏ·Ù˘ÛÌ¤ÓË Ì‡ÙË, ¯·ÌËÏ¿ ÚÔ¤¯ÔÓÙ· ÒÙ·, ‚Ú·¯˘Ï·ÈÌ›·, ·˘¯ÂÓÈÎfi ÙÂÚ‡ÁÈÔ, ÛÎ·ÊÔÂÈ‰¤˜ ÛÙ¤ÚÓÔ Î·È ÛÎÔÏ›ˆÛË). √ ÌÔÚÈ·Îfi˜ ÁÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÈ‚Â‚·›ˆÛÂ ÙËÓ ÎÏÈÓÈÎ‹ ‰È¿ÁÓˆÛË Î·È ·ÔÎ¿Ï˘„Â fiÙÈ ÚfiÎÂÈÙ·È ÁÈ· ÌËÙÚÈÎ‹ ÌÂÙ·‚›‚·ÛË ÙË˜ ÂÙÂÚfi˙˘ÁË˜ ·ÚÂÚÌËÓÂ‡ÛÈÌË˜ ÌÂÙ¿ÏÏ·ÍË˜ A188G ÛÙÔ ÂÍfiÓÈÔ 3 ÙÔ˘ ÁÔÓÈ‰›Ô˘ PTPN 11. ∏ ›‰È· ÌÂÙ¿ÏÏ·ÍË ·ÓÂ‚Ú¤ıËÎÂ Î·È ÛÙÔÓ ıÂ›Ô ·fi ÙË ÌËÙ¤Ú·. ∆· ÎÏÈÓÈÎÔÂÚÁ·ÛÙËÚÈ·Î¿ Î·È Ù· Â˘Ú‹Ì·Ù· ÙË˜ ÌÔÚÈ·Î‹˜ ·Ó¿Ï˘ÛË˜ Û˘Û¯ÂÙ›˙ÔÓÙ·È ÌÂ Ù· ‚È‚ÏÈÔÁÚ·ÊÈÎ¿ ‰Â‰ÔÌ¤Ó· Î·È ‰›‰ÂÙ·È ¤ÌÊ·ÛË ÛÙËÓ ÂÓ‰ÔÔÈÎÔÁÂÓÂÈ·Î‹ ÔÈÎÈÏÔÌÔÚÊ›·, Ë ÔÔ›· Î·ıÈÛÙ¿ ·Ó·ÁÎ·›· ÙË ‰ÈÂÓ¤ÚÁÂÈ· ÌÔÚÈ·ÎÔ‡ ÁÂÓÂÙÈÎÔ‡ ÂÏ¤Á¯Ô˘ ÛÙÈ˜ ÂÚÈÙÒÛÂÈ˜ ·˘Ù¤˜ ÁÈ· ÙËÓ ÏËÚ¤ÛÙÂÚË ÁÂÓÂÙÈÎ‹ Î·ıÔ‰‹ÁËÛË.

∂ÚÁ·ÛÙ‹ÚÈÔ π·ÙÚÈÎ‹˜ °ÂÓÂÙÈÎ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ∞’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, °’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ AÏÏËÏÔÁÚ·Ê›·: ™ÔÊ›· ∫›ÙÛÈÔ˘-∆˙¤ÏË ∂ÚÁ·ÛÙ‹ÚÈÔ π·ÙÚÈÎ‹˜ °ÂÓÂÙÈÎ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∏ ∞Á›· ™ÔÊ›·” ∆∫ 115 27, ∞ı‹Ó· E-mail: skitsiou@med.uoa.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 24-11-05 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 21-07-06

§¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ™‡Ó‰ÚÔÌÔ Noonan, ÁÔÓ›‰ÈÔ PTPN 11, ÎÏÈÓÈÎ‹ ÂÙÂÚÔÁ¤ÓÂÈ·.

Molecular, clinical and laboratory investigation in a Noonan syndrome family presenting with clinical variability S. Kitsiou - Tzeli, A. Papadopoulou, A. Xaidara, G. Papadopoulos, A.-M. Magiakou, A. Kolialexi, A. Mavrou, E. Kanavakis, P. Nikolaidou

Abstract: ¡ÔÔnan syndrome (NS) is a relatively common autosomal dominant genetic disorder with great clinical variability. It is characterized by craniofacial anomalies, short stature, congenital heart defects, cryptorchidism, skeletal and other organ malformations, bleeding diathesis and mental retardation. Mutations of the PTNP 11 gene have been identified in 33-60% of cases. A family is reported with NS transmitted through 3 maternal generations. The five affected members presented with different organ involvement. The index case, a 4 year-old girl with growth retardation, is the product of a twin IVF pregnancy. Her phenotypic characteristics, common to all the affected members, include: coarse triangular-shaped face, hypertelorism, down-slanting prominent eyes with epicanthus, low-set posteriorly angulated ears with thickened helices, bulbous nasal tip, big mouth with arched upper lip, short webbed neck, pectus excavatum and scoliosis. She was operated on for pulmonary stenosis, as was her twin sister who died following surgery. Their mother had a delayed menarche and a history of bleeding diathesis. A maternal uncle has a heart murmur. The grandmother died at the age of 30 years from a heart attack. The molecular investigation revealed a maternally transmitted heterozygous missense mutation A 118 G in exon 3, which was also observed in the maternal uncle. The intrafamiliar variability

Department of Medical Genetics, First Department of Pediatrics, Third Department of Pediatrics, Athens University, Athens Greece Correspondence: Sofia Kitsiou-Tzeli, Department of Medical Genetics, “Aghia Sophia” Children’s Hospital 115 27 Athens, Greece E-mail: skitsiou@med.uoa.gr Date of submission: 24-11-05 Date of approval: 21-07-06

¶·È‰È·ÙÚÈÎ‹ 2006;69:447-451

448

™. ∫›ÙÛÈÔ˘-∆˙¤ÏË Î·È Û˘Ó.

of NS makes it essential for first degree relatives, even with an atypical phenotype, to be screened for PTNP 11 gene mutations in order to receive appropriate genetic counseling.

Key words: Noonan syndrome, PTNP 11 gene, clinical variability.

∏ ÌÔÚÈ·Î‹ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Noonan (1) Â›Ó·È È‰È·›ÙÂÚ· ÛËÌ·ÓÙÈÎ‹ ·ÊÔ‡ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÔÈÎ›ÏË ÎÏÈÓÈÎ‹ ÂÎÊÚ·ÛÙÈÎfiÙËÙ· (2), ÔÈ ¿Û¯ÔÓÙÂ˜ ‰‡ÛÎÔÏ· ·Ó·ÁÓˆÚ›˙ÔÓÙ·È ÛÙË ‚ÚÂÊÈÎ‹ ËÏÈÎ›·, ÂÓÒ Ù· ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ ÙÔ˘ ÚÔÛÒÔ˘ Â›Ó·È ÂÌÊ·Ó¤ÛÙÂÚ· ÛÙËÓ ·È‰ÈÎ‹ ËÏÈÎ›· Î·È ÌÂ ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘ ÌÔÚÔ‡Ó Ó· Á›ÓÔ˘Ó ËÈfiÙÂÚ· (“ÌÂÙ·‚·ÏÏfiÌÂÓÔ˜ Ê·ÈÓfiÙ˘Ô˜”). ∂› ÌË Ù˘ÈÎÔ‡ Ê·ÈÓÔÙ‡Ô˘ ÙÔ ÏÂÙÔÌÂÚ¤˜ ÈÛÙÔÚÈÎfi Î·ÙÂ˘ı‡ÓÂÈ ÙË ‰È¿ÁÓˆÛË. π‰È·›ÙÂÚË ¤ÌÊ·ÛË ‰›ÓÂÙ·È ÛÙËÓ ·Ó·˙‹ÙËÛË Û˘ÁÁÂÓÔ‡˜ Î·Ú‰ÈÔ¿ıÂÈ·˜ ‹/Î·È ¯·ÌËÏÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜ ÛÂ ¿ÏÏ· Ì¤ÏË ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ ÙÔ˘ ÚÔÛ‚Â‚ÏËÌ¤ÓÔ˘ ·È‰ÈÔ‡. ¶·ÚÔ˘ÛÈ¿˙ÂÙ·È Ë ‰È·ÁÓˆÛÙÈÎ‹ ÚÔÛ¤Ï·ÛË ·ÛıÂÓÔ‡˜ ÌÂ Ê·ÈÓfiÙ˘Ô Û˘Ó‰ÚfiÌÔ˘ Noonan (¡S) Ô˘ ÂÈÛ‹¯ıË ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ÙË ‰ÈÂÚÂ‡ÓËÛË Î·ı˘ÛÙ¤ÚËÛË˜ ÛˆÌ·ÙÈÎ‹˜ ·Ó¿Ù˘ÍË˜. √ ÌÔÚÈ·Îfi˜ ÁÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ ·ÔÎ¿Ï˘„Â ÙË ÌÂÙ¿ÏÏ·ÍË ∞188G ÛÙÔ ÂÍfiÓÈÔ 3 ÙÔ˘ ÁÔÓÈ‰›Ô˘ PTPN 11 ÛÙËÓ ·ÛıÂÓ‹, ÙË ÌËÙ¤Ú· ÙË˜ Î·È ÙÔÓ ÌËÙÚÈÎfi ıÂ›Ô.

ÓÈÎ‹˜. ™Â ËÏÈÎ›· 13 ÌËÓÒÓ ˘Â‚Ï‹ıË ÛÂ Î·Ú‰ÈÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô Î·ıÒ˜ Î·È Î·Ú‰È·Îfi Î·ıÂÙËÚÈ·ÛÌfi Î·È ‚·Ï‚È‰ÔÏ·ÛÙÈÎ‹ ÌÂ Ì·ÏfiÓÈ, ÏfiÁˆ ÛÙ¤ÓˆÛË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ‚·Ï‚›‰·˜ ÔÊÂÈÏfiÌÂÓË˜ ÛÂ ‰˘ÛÏ·Û›· ·˘Ù‹˜. ∫·Ù¿ ÙÔÓ ÌÂÙÂÁ¯ÂÈÚËÙÈÎfi ¤ÏÂÁ¯Ô ÌÂ Triplex Î·Ú‰È¿˜, ‰È·ÈÛÙÒıËÎÂ ‰˘ÛÏ·ÛÙÈÎ‹ ÓÂ˘ÌÔÓÈÎ‹ ‚·Ï‚›‰· ÌÂ Èı·ÓÒ˜ ˘ÂÚ‚·Ï‚È‰ÈÎfi ÛÙÔÈ¯Â›Ô Ì¤ÙÚÈ·˜ ÛÙ¤ÓˆÛË˜. ™ÙËÓ ËÏÈÎ›· ÙˆÓ 4 ÂÙÒÓ ·Ú·¤ÌÊıËÎÂ ÛÙÔ π·ÙÚÂ›Ô ∫ÏÈÓÈÎ‹˜ °ÂÓÂÙÈÎ‹˜ ÁÈ· ¤ÏÂÁ¯Ô ·ÓÂ·ÚÎÔ‡˜ ÛˆÌ·ÙÈÎ‹˜ ·Ó¿Ù˘ÍË˜, ÂÓÒ Ë „˘¯ÔÎÈÓËÙÈÎ‹ ÙË˜ ÂÍ¤ÏÈÍË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎ‹. ∫·Ù¿ ÙËÓ ÎÏÈÓÈÎ‹ ÁÂÓÂÙÈÎ‹ ÂÎÙ›ÌËÛË ÚÔ¤Î˘„·Ó ÔÈ ·ÎfiÏÔ˘ıÂ˜ ÛˆÌ·ÙÔÌÂÙÚÈÎ¤˜ ·Ú¿ÌÂÙÚÔÈ: ª™: 95 cm (<3Ë ∂£), µ™: 13 kg (3Ë-5Ë ∂£), Î·È ¶∫: 50 cm (50‹ ∂£). ∏ ·ÛıÂÓ‹˜ ÂÌÊ¿ÓÈ˙Â ÙÚÈÁˆÓÈÎfi ÚfiÛˆÔ, ˘ÂÚÙÂÏÔÚÈÛÌfi, Â›Î·ÓıÔ, Ô›‰ËÌ· ‚ÏÂÊ¿ÚˆÓ, ·ÓÙÈÌÔÁÁÔÏÔÂÈ‰Â›˜ ‚ÏÂÊ·ÚÈÎ¤˜ Û¯ÈÛÌ¤˜, ÂÏ·ÊÚ¿ ‚ÏÂÊ·ÚfiÙˆÛË ÌÂ ÚÔ¤¯ÔÓÙÂ˜ ÔÊı·ÏÌÔ‡˜, Ì‡ÙË ‚ÔÏ‚Ò‰Ë, ÚÔ¤¯ÔÓÙ· ÒÙ· ÌÂ ¯·ÌËÏ‹ ÚfiÛÊ˘ÛË, ÏÔÍ‹ ÊÔÚ¿ Î·È ·¯È¿ ¤ÏÈÎ·, ÌÂÁ¿ÏÔ ÛÙfiÌ· ÌÂ ¯Â›ÏÔ˜ ÙÔÍˆÙfi, ˘„ËÏ‹ ˘ÂÚÒ·, ·˘¯ÂÓÈÎfi ÙÂÚ‡ÁÈÔ Î·È ‚Ú·¯‡ Ï·ÈÌfi. ™ÙÔÓ ıÒÚ·Î· ·Ú·ÙËÚ‹ıËÎÂ ÛÎ·ÊÔÂÈ‰¤˜ ÛÙ¤ÚÓÔ, ˘ÔÏ·ÛÙÈÎ¤˜ ıËÏ¤˜ ÌÂ ÌÂÁ¿ÏË ÌÂÙ·Í‡ ÙÔ˘˜ ·fiÛÙ·ÛË Î·È ÛÎÔÏ›ˆÛË. ∏ ÌËÙ¤Ú· ÙË˜ ·ÛıÂÓÔ‡˜ (ππ:2) ËÏÈÎ›·˜ 39 ÂÙÒÓ, ¤¯ÂÈ ‡„Ô˜ 142 cm Î·È ÂÌÊ·Ó›˙ÂÈ Ù· ÂÍ‹˜ Ê·ÈÓÔÙ˘ÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿: ÙÚÈÁˆÓÈÎfi ÚfiÛˆÔ, ˘ÂÚÙÂÏÔÚÈÛÌfi, Â›Î·ÓıÔ, ÛËÌ·ÓÙÈÎfi

¶ÂÚÈÁÚ·Ê‹ ÂÚÈÙÒÛÂˆÓ

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ NS ¡ÔÔnan Syndrome PTPN 11 Protein-Tyrosine Phosphatase, Nonreceptor-type, 11-OMIM#163950 ∂£ ∂Î·ÙÔÛÙÈ·›· ı¤ÛË DGGE Denaturing Gradient Gel Electrophoresis

∂ÈÛ·ÁˆÁ‹

∏ ·ÛıÂÓ‹˜ - ‰Â›ÎÙË˜ (πππ:1) Â›Ó·È ÙÔ ÌÔÓ·‰ÈÎfi ·È‰› ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ (∂ÈÎfiÓ· 1). °ÂÓÓ‹ıËÎÂ ÌÂ Î·ÈÛ·ÚÈÎ‹ ÙÔÌ‹ ÏfiÁˆ ‰›‰˘ÌË˜ Î‡ËÛË˜ Ë ÔÔ›· ‰È‹ÚÎÂÛÂ 34 Â‚‰ÔÌ¿‰Â˜. ∫·Ù¿ ÙË Á¤ÓÓËÛË ÙÔ ‚¿ÚÔ˜ ÙË˜ ·ÛıÂÓÔ‡˜ ‹Ù·Ó 2030 g (25Ë ∂£), ÙÔ Ì‹ÎÔ˜ ÛÒÌ·ÙÔ˜ 44 cm (50Ë ∂£) Î·È Ë ÂÚ›ÌÂÙÚÔ˜ ÎÂÊ·Ï‹˜ 31,5 cm (50‹ ∂£). §fiÁˆ ÙË˜ ÚÔˆÚfiÙËÙ·˜ Î·È Èı·Ó‹˜ ÂÌ‚Ú˘ÔÂÌ‚Ú˘˚Î‹˜ ÌÂÙ¿ÁÁÈÛË˜ ÓÔÛËÏÂ‡ıËÎÂ ÛÂ ªÔÓ¿‰· ∂ÓÙ·ÙÈÎ‹˜ ¡ÔÛËÏÂ›·˜ ÁÈ· 25 ËÌ¤ÚÂ˜. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ÓÔÛËÏÂ›·˜ ‰È·ÈÛÙÒıËÎÂ Û˘ÛÙÔÏÈÎfi Ê‡ÛËÌ· 2/6 ÌÂ ¯·Ú·ÎÙ‹ÚÂ˜ ÂÚÈÊÂÚÈÎ‹˜ ÛÙ¤ÓˆÛË˜ ÓÂ˘ÌÔ¶·È‰È·ÙÚÈÎ‹ 2006;69:447-451

II 1

III 1

∂ÈÎﬁÓ· 1. ∆Ô ÁÂÓÂ·ÏÔÁÈÎﬁ ‰¤Ó‰ÚÔ ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜.

449

√ÈÎÔÁ¤ÓÂÈ· ÌÂ ÂÙÂÚÔÁ¤ÓÂÈ· Û˘Ó‰ÚﬁÌÔ˘ Noonan

Ô›‰ËÌ· ‚ÏÂÊ¿ÚˆÓ, ‚ÏÂÊ·ÚfiÙˆÛË, ·ÓÙÈÌÔÁÁÔÏÔÂÈ‰Â›˜ ‚ÏÂÊ·ÚÈÎ¤˜ Û¯ÈÛÌ¤˜, ÛËÌ·ÓÙÈÎ‹ ÚÔ¤ÙÂÈ· ÔÊı·ÏÌÈÎÒÓ ‚ÔÏ‚ÒÓ, ˘ÂÚÌÂÙÚˆ›·, ‚ÔÏ‚Ò‰Ë Ì‡ÙË, ¯·ÌËÏ‹ ÚfiÛÊ˘ÛË ÒÙˆÓ ÌÂ ÏÔÍ‹ ÊÔÚ¿, ·ÓÒÌ·ÏË ÂÏ›ÎˆÛË Î·È ·¯È¿ ¤ÏÈÎ·, ÌÂÁ¿ÏÔ ÛÙfiÌ· ÌÂ ÙÔÍˆÙ¿ ¯Â›ÏË Î·È ˘„ËÏ‹ ˘ÂÚÒ·, ‚Ú·¯‡ Ï·ÈÌfi ÌÂ ·˘¯ÂÓÈÎfi ÙÂÚ‡ÁÈÔ Î·È Î˘ÊÔÛÎÔÏ›ˆÛË. √ Î·Ú‰ÈÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÛÙÔÓ ÔÔ›Ô ˘Â‚Ï‹ıË Ë ÌËÙ¤Ú· ‰ÂÓ ¤‰ÂÈÍÂ ·ıÔÏÔÁÈÎ¿ Â˘Ú‹Ì·Ù·. ™ÙÔ ·ÙÔÌÈÎfi ÙË˜ ·Ó·ÌÓËÛÙÈÎfi ·Ó·Ê¤ÚÔÓÙ·È ÓÔÛËÏÂ›Â˜ ÏfiÁˆ ÂÎÛÂÛËÌ·ÛÌ¤ÓË˜ ·ÈÌÔÚÚ·Á›·˜ Î·Ù¿ ÙËÓ ‰È¿ÚÎÂÈ· ·ÏÒÓ ÁÓ·ıÔ¯ÂÈÚÔ˘ÚÁÈÎÒÓ ÂÂÌ‚¿ÛÂˆÓ ÏfiÁˆ ·ÓÒÌ·ÏË˜ ¤ÎÊ˘ÛË˜ Ô‰fiÓÙˆÓ, ÂÌÌËÓ·Ú¯‹ ÛÂ ËÏÈÎ›· 16 ¯ÚfiÓˆÓ Î·È ˘ÔÁÔÓÈÌfiÙËÙ·. ø˜ ÂÎ ÙÔ‡ÙÔ˘ Î·Ù¤Ê˘ÁÂ ÛÙËÓ ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË, ÚÔ˚fiÓ ÙË˜ ÔÔ›·˜ ‹Ù·Ó Ë ‰›‰˘ÌË Î‡ËÛË. ∏ ‰›‰˘ÌË ·‰ÂÏÊ‹ (πππ:2) ÙË˜ ·ÛıÂÓÔ‡˜-‰Â›ÎÙË, Ë ÔÔ›· Î·Ù¤ÏËÍÂ ÛÂ ËÏÈÎ›· 9 ÌËÓÒÓ ÌÂÙ¿ ·fi ‰ÈÔÚıˆÙÈÎ‹ Â¤Ì‚·ÛË ÛÙ¤ÓˆÛË˜ ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜, Â›¯Â ·ÚfiÌÔÈÔ Ê·ÈÓfiÙ˘Ô. ∏ ÁÈ·ÁÈ¿ ·fi ÙË ÌËÙ¤Ú· (π:4), Ë ÔÔ›· Â›¯Â Ù· ›‰È· ÌÔÚÊÔÏÔÁÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ ÌÂ ÙËÓ ÎfiÚË (ππ:2) Î·È ÙÈ˜ ‰›‰˘ÌÂ˜ ÂÁÁÔÓ¤˜ (πππ:1 Î·È πππ:2), Î·Ù¤ÏËÍÂ ÛÂ ËÏÈÎ›· 30 ÂÙÒÓ ·fi “·Ó·ÎÔ‹ Î·Ú‰È¿˜”. ∆· ›‰È· Â›ÛË˜ ÌÔÚÊÔÏÔÁÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ ÂÌÊ·Ó›˙ÂÈ Î·È Ô ıÂ›Ô˜ ·fi ÙË ÌËÙ¤Ú· (ππ:3), ÙË˜ ·ÛıÂÓÔ‡˜-‰Â›ÎÙË, Ô ÔÔ›Ô˜ ¤¯ÂÈ ‡„Ô˜ 170 cm Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ “Ê‡ÛËÌ· ÚÔÎ·Ú‰›Ô˘”, ¯ˆÚ›˜ Ó· ¤¯ÂÈ ˘Ô‚ÏËıÂ› ÛÂ ÂÈ‰ÈÎfi ¤ÏÂÁ¯Ô. ∆· Ê·ÈÓÔÙ˘ÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È Ê·›ÓÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 1 Î·È ÛÙÈ˜ ∂ÈÎfiÓÂ˜ 2 Î·È 3.

∫ÏÈÓÈÎÔÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ∏ ·ÛıÂÓ‹˜ ˘Â‚Ï‹ıË ÛÂ Î·Ú‰ÈÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô Î·È ‰È·ÈÛÙÒıËÎÂ ‚·Ï‚È‰ÔÏ·ÛÙÈÎ‹ ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÌÂ ËÈfiÙ·ÙË ÛÙ¤ÓˆÛË. ∆Ô ˘ÂÚÔ¯ËÁÚ¿ÊËÌ· ¿Óˆ - Î¿Ùˆ ÎÔÈÏ›·˜ Î·È ÁÂÓÓËÙÈÎÒÓ ÔÚÁ¿ÓˆÓ, Ô ÔÊı·ÏÌÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜, Ô ¤ÏÂÁ¯Ô˜ ·ÈÌÔÚÚ·ÁÈÎ‹˜ ‰È¿ıÂÛË˜ (¯ÚfiÓÔ˜ ÚÔıÚÔÌ‚›ÓË˜, ¯ÚfiÓÔ˜ ıÚÔÌ‚›ÓË˜, ∞ƒ∆∆, ÈÓˆ‰ÔÁfiÓÔ, ·Ú¿ÁÔÓÙÂ˜ ‹ÍË˜), Î·È Ô ÂÓ‰ÔÎÚÈÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ (GH, IGF1, FSH, LH, PRL, T3, T4, TSH, ÔÈÛÙÚ·‰ÈfiÏË, ÙÂÛÙÔÛÙÂÚfiÓË, ÚÔÁÂÛÙÂÚfiÓË, DHEA-S, 17-OH ÚÔÁÂÛÙÂÚfiÓË, ‰ÔÎÈÌ·Û›· ‰È¤ÁÂÚÛË˜ ÌÂ ÁÏ˘Î·ÁfiÓË) Â›¯·Ó Ê˘ÛÈÔÏÔÁÈÎ¿ Â˘Ú‹Ì·Ù·. °ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ √ Î·Ú˘fiÙ˘Ô˜ ÙË˜ ·ÛıÂÓÔ‡˜ ¤‰ÂÈÍÂ Ê˘ÛÈÔÏÔÁÈÎ‹ ¯ÚˆÌÔÛˆÌÈÎ‹ Û‡ÛÙ·ÛË ı‹ÏÂÔ˜ (46,ÃÃ). ∏ ·Ó¿Ï˘ÛË ÙÔ˘ ÁÔÓÈ‰›Ô˘ PTPN 11 ¤ÁÈÓÂ ÛÙËÓ ·ÛıÂÓ‹ (πππ:1), ÛÙÔ˘˜ ÁÔÓÂ›˜ (ππ:1 Î·È II:2), Î·È ÛÙÔÓ ÌËÙÚÈÎfi ıÂ›Ô (II:3), ÌÂÙ¿ ·fi ·ÔÌfiÓˆÛË DNA ·fi ÂÚÈÊÂÚÈÎfi ·›Ì·. ∂Ê·ÚÌfiÛÙËÎÂ Ë ·ÓÙ›‰Ú·ÛË PCR ÌÂ Î·Ù¿ÏÏËÏÔ˘˜ ÂÎÎÈÓËÙ¤˜ Ô˘ ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙ· 15 ÂÍfiÓÈ· ÙÔ˘ ÁÔÓÈ‰›Ô˘ (3). ∏ ·ÎÔÏÔ˘ı›· ÙˆÓ ÓÔ˘ÎÏÂÔÙÈ‰›ˆÓ ÁÈ· ÙËÓ ·Ó›¯ÓÂ˘ÛË Èı·ÓÒÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ·Ó·Ï‡ıËÎÂ ÛÂ ·˘ÙfiÌ·ÙÔ ·Ó·Ï˘Ù‹ (Visgen Sequencer). ∞Ó·˙ËÙ‹ıËÎ·Ó ÌÂÙ·ÏÏ¿ÍÂÈ˜ ‹ ÔÏ˘ÌÔÚÊÈÛÌÔ› ÛÙ· ÂÍfiÓÈ· Î·È ÛÙÈ˜ ÂÚÈÔ¯¤˜ Û‡Ó‰ÂÛ‹˜ ÙÔ˘˜ ÌÂ Ù· ·ÓÙ›ÛÙÔÈ¯· ÂÛfiÓÈ· (Ì¤ıÔ‰Ô˜ Denaturing Gradient Gel Electrophoresis, DGGE). ™Â ‰Â›ÁÌ·Ù· ÛÙ· ÔÔ›· ·Ú·ÙËÚ‹ıËÎÂ ÚfiÙ˘Ô ËÏÂÎÙÚÔÊfiÚËÛË˜ ‰È·ÊÔÚÂÙÈÎfi ·fi ·˘Ùfi ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ Ì·ÚÙ‡ÚˆÓ (controls) -ÔfiÙÂ ˘Ô‰ËÏÒÓÂÙ·È Èı·Ó‹ ·ÚÔ˘Û›· ÌÂÙ¿ÏÏ·ÍË˜ ‹ ÔÏ˘ÌÔÚÊÈÛÌÔ‡- ·˘ÙÔ› ÚÔÛ‰ÈÔÚ›ÛÙËÎ·Ó ÂÚ·ÈÙ¤Úˆ ÌÂ ·ÏÏËÏÔ˘¯ÔÔ›ËÛË

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∂ÈÎﬁÓ· 3. ∏ ·ÛıÂÓ‹˜-‰Â›ÎÙË˜ (III:1) ÛÂ ËÏÈÎ›· 4 ÂÙÒÓ ÌÂ ÙË ÌËÙ¤Ú· ÙË˜ (ππ:2). ∂ÈÎﬁÓ· 2. √È ‰›‰˘ÌÂ˜ ·‰ÂÏÊ¤˜ (III:1 Î·È III:2) ÛÂ ËÏÈÎ›· 6 ÌËÓÒÓ.

™˘˙‹ÙËÛË ∆Ô NS ÂÚÈÁÚ¿ÊËÎÂ ÁÈ· ÚÒÙË ÊÔÚ¿ ÙÔ 1963 ·fi ÙËÓ ·È‰ÔÎ·Ú‰ÈÔÏfiÁÔ Jacqueline Noonan ÛÙÔ ¿ÚıÚÔ “Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease”. (4) ™‹ÌÂÚ· ÙÔ NS Â›Ó·È ÁÓˆÛÙfi ˆ˜ ÁÔÓÈ‰È·Îfi ÓfiÛËÌ· ÌÂ ÂÈÎÚ·ÙËÙÈÎfi ¯·Ú·ÎÙ‹Ú·, ÈÛfiÙÈÌË ÚÔÛ‚ÔÏ‹ ÙˆÓ ‰‡Ô Ê‡ÏˆÓ Î·È Ê˘ÛÈÔÏÔÁÈÎfi Î·Ú˘fiÙ˘Ô (5,6). ∏ Û˘¯ÓfiÙËÙ· ÙÔ˘ NS Î˘Ì·›ÓÂÙ·È ·fi 1:100 ¤ˆ˜ 1:1000, ÂÓÒ ·ÔÙÂÏÂ› ÙË ‰Â‡ÙÂÚË Î·Ù¿ ÛÂÈÚ¿ ÁÂÓÂÙÈÎ‹ ‰È·Ù·Ú·¯‹ Ô˘ Û˘Ó‰˘¿˙ÂÙ·È ÌÂ Û˘ÁÁÂÓ‹ Î·Ú‰ÈÔ¿ıÂÈ· ÌÂÙ¿ ÙÔ Û‡Ó‰ÚÔÌÔ Down (7). ∏ Û˘ÁÁÂÓ‹˜ Î·Ú‰ÈÔ¿ıÂÈ· ÂÌÊ·Ó›˙ÂÙ·È ÛÙÔ Û‡Ó‰ÚÔÌÔ ÌÂ Û˘¯ÓfiÙËÙ· 86%, ÌÂ Û˘¯ÓfiÙÂÚË ÙËÓ ÛÙ¤ÓˆÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ‚·Ï‚›‰·˜, ÙËÓ ˘ÂÚÙÚÔÊÈÎ‹ Ì˘ÔÎ·Ú‰ÈÔ¿ıÂÈ· Î·È ÙÔ ÌÂÛÔÎÔÏÈÎfi ¤ÏÏÂÈÌÌ· (7,8). ∏ ÔÈÎ›ÏË ÂÎÊÚ·ÛÙÈÎfiÙËÙ· Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÈ ÙÔ Û‡Ó‰ÚÔÌÔ, Û˘¯Ó¿ ‰ÂÓ ÂÈÙÚ¤ÂÈ ÙËÓ ·Ó·ÁÓÒÚÈÛË ÂÓËÏ›ÎˆÓ ÌÂ ‹È· ÎÏÈÓÈÎ‹ ÂÈÎfiÓ·, ‰ÈfiÙÈ Â›Ó·È ÁÓˆÛÙfi fiÙÈ ÔÈ ÎÚ·ÓÈÔÚÔÛˆÈÎ¤˜ ·ÓˆÌ·Ï›Â˜ ÌÂÙ·‚¿ÏÏÔÓÙ·È ÌÂ ÙËÓ ËÏÈÎ›· Î·È Â›Ó·È ÏÈÁfiÙÂÚÔ ÂÌÊ·ÓÂ›˜ ÛÙÔ˘˜ ÂÓ‹ÏÈÎÂ˜ (2). ∆Ô ÁÂÁÔÓfi˜ ·˘Ùfi ‰˘Û¯ÂÚ·›¶·È‰È·ÙÚÈÎ‹ 2006;69:447-451

∂ÍﬁÌÈÔ 3

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ÙÔ˘ DNA ÙË˜ ÂÚÈÔ¯‹˜ (sequencing). ™ÙÔÓ ·Ù¤Ú· ÙË˜ ·ÛıÂÓÔ‡˜ (ππ:1) ‰ÂÓ ·ÓÂ‚Ú¤ıËÎÂ ÌÂÙ¿ÏÏ·ÍË, ÂÓÒ ÛÙ· ˘fiÏÔÈ· 3 Ì¤ÏË ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ Ô˘ ÂÏ¤Á¯ıËÎ·Ó (ππ:2, ππ:3, πππ:1) ‰È·ÈÛÙÒıËÎÂ Ë ÂÙÂÚfi˙˘ÁË ·ÚÂÚÌËÓÂ‡ÛÈÌË (missense) ÌÂÙ¿ÏÏ·ÍË A188G ÛÙÔ ÂÍfiÓÈÔ 3. ∂ÈÚÔÛı¤Ùˆ˜, ÛÙËÓ ·ÛıÂÓ‹-‰Â›ÎÙË ‚Ú¤ıËÎÂ ÔÏ˘ÌÔÚÊÈÛÌfi˜ 21C→T ÛÙÔ ¿ÎÚÔ 3 ÙÔ˘ ÂÛoÓ›Ô˘ 7, Ô ÔÔ›Ô˜ ·Ô˘ÛÈ¿˙ÂÈ ·fi ÙË ÌËÙ¤Ú· Î·È ÙÔÓ ·Ù¤Ú· (de novo) (∂ÈÎfiÓ· 4).

ÓÂÈ ÙË ÁÂÓÂÙÈÎ‹ Û˘Ì‚Ô˘ÏÂ˘ÙÈÎ‹, ‰Â‰ÔÌ¤ÓÔ˘ fiÙÈ, fiÙ·Ó ÛÙÔÓ ¤Ó· ÂÎ ÙˆÓ ‰‡Ô ÁÔÓ¤ˆÓ Ë ÎÏÈÓÈÎ‹ ÂÈÎfiÓ· Â›Ó·È Ù˘ÈÎ‹, Ô ÁÂÓÂÙÈÎfi˜ Î›Ó‰˘ÓÔ˜ Â·Ó¿ÏË„Ë˜ (50%) ÌÔÚÂ› Ó· ‰ÔıÂ› ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ·, ÂÓÒ fiÙ·Ó ÔÈ ÁÔÓÂ›˜ ÂÌÊ·Ó›˙Ô˘Ó Ï›Á· ‹/Î·È ¿Ù˘· Â˘Ú‹Ì·Ù· ÙÔ˘ NS, Ô Î›Ó‰˘ÓÔ˜ Â·Ó¿ÏË„Ë˜ Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ÚÔ‚ÏÂÊıÂ›. ™ÙÈ˜ ÂÚÈÙÒÛÂÈ˜ ·˘Ù¤˜ Â›Ó·È ··Ú·›ÙËÙÔ˜ Ô ÌÔÚÈ·Îfi˜ ÁÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· ÙËÓ ÂÈ‚Â‚·›ˆÛË ÙË˜ ÎÏÈÓÈÎ‹˜ ‰È¿ÁÓˆÛË˜ (3). ∆Ô ˘Â‡ı˘ÓÔ ÁÈ· ÙÔ NS ÁÔÓ›‰ÈÔ PTPN 11 (Protein-Tyrosine Phosphatase, Nonreceptortype 11) ¯·ÚÙÔÁÚ·Ê‹ıËÎÂ ÙÔ 1994 ·fi ÙÔ˘˜ Jamieson et al (9) ÛÙÔ Ì·ÎÚfi ÛÎ¤ÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 12(q24.1). ∆Ô ÁÔÓ›‰ÈÔ ¤¯ÂÈ Ì‹ÎÔ˜ 4 cM Î·È ·ÔÙÂÏÂ›Ù·È ·fi 15 ÂÍfiÓÈ· Ô˘ Îˆ‰ÈÎÔÔÈÔ‡Ó ÙËÓ ÚˆÙÂ˝ÓË SHP-2. ∏ ÚˆÙÂ˝ÓË ·˘Ù‹ Â›Ó·È ÛËÌ·ÓÙÈÎ‹ ÁÈ· ÙÔÓ ÛˆÛÙfi Û¯ËÌ·ÙÈÛÌfi ÙˆÓ ÈÛÙÒÓ Î·Ù¿ ÙËÓ ·Ó¿Ù˘ÍË ·ÏÏ¿ Î·È ÁÈ· ÙË ‰È·›ÚÂÛË, ÂÍÂÈ‰›ÎÂ˘ÛË Î·È Î›ÓËÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ

∂ÈÎﬁÓ· 4. °ÔÓÔÙ˘ÈÎ‹ ·Ó¿Ï˘ÛË ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜: a=·ÛıÂÓ‹˜ - ‰Â›ÎÙË˜ (πππ:1), b=ÌËÙ¤Ú· (ππ:2), c=·Ù¤Ú·˜ (ππ:1).

451

√ÈÎÔÁ¤ÓÂÈ· ÌÂ ÂÙÂÚÔÁ¤ÓÂÈ· Û˘Ó‰ÚﬁÌÔ˘ Noonan

Î·È ÂÎÊÚ¿˙ÂÙ·È Î˘Ú›ˆ˜ ÛÙËÓ Î·Ú‰È¿, ÙÔÓ ÂÁÎ¤Ê·ÏÔ Î·È ÙÔ˘˜ ÛÎÂÏÂÙÈÎÔ‡˜ Ì˘˜ (10). √È ÂÚÈÛÛfiÙÂÚÂ˜ ÌÂÙ·ÏÏ¿ÍÂÈ˜ ÙÔ˘ ÁÔÓÈ‰›Ô˘ ƒ∆ƒ¡ 11 ÚÔÎ·ÏÔ‡Ó ÌÂÙ·‚ÔÏ‹ ÛÙËÓ ·ÏÏËÏÔ˘¯›· ÙˆÓ ·ÌÈÓÔÍ¤ˆÓ ÙË˜ ÚˆÙÂ˝ÓË˜ SHP2, ÌÂ Â·ÎfiÏÔ˘ıÔ ÙË Û˘ÓÂ¯‹ ÂÓÂÚÁÔÔ›ËÛË ÙË˜ ÚˆÙÂ˝ÓË˜. ∏ ‰È·ÚÎÒ˜ ÂÓÂÚÁÔÔÈËÌ¤ÓË ÚˆÙÂ˝ÓË ·ÔÚ˘ıÌ›˙ÂÈ Ù· Û˘ÛÙ‹Ì·Ù· ÂÏ¤Á¯Ô˘ ÙˆÓ Î˘ÙÙ·ÚÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ ·Ó¿Ù˘ÍË˜ Î·È ‰È·›ÚÂÛË˜ ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÌÊ¿ÓÈÛË ÙˆÓ ÛËÌÂ›ˆÓ Î·È ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ÙÔ˘ NS (10). ªÂÙ·ÏÏ¿ÍÂÈ˜ ÛÙÔ ƒ∆ƒ¡ 11 ¤¯Ô˘Ó ·ÓÈ¯ÓÂ˘ıÂ› ÛÂ ÔÛÔÛÙfi 33-60% ÙˆÓ ·ÛıÂÓÒÓ ÌÂ NS, ¤¯Ô˘Ó ‰Â ÂÚÈÁÚ·ÊÂ› ÂÚÈÛÛfiÙÂÚÂ˜ ·fi 30 ‰È·ÊÔÚÂÙÈÎ¤˜, ·ÚÂÚÌËÓÂ‡ÛÈÌÂ˜ Î˘Ú›ˆ˜, ÌÂÙ·ÏÏ¿ÍÂÈ˜ (11). ™ÙËÓ ÔÈÎÔÁ¤ÓÂÈ· Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È, ÂÌÊ·Ó›˙ÂÙ·È ÛÙ¤ÓˆÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ÛÙÈ˜ ‰‡Ô ‰›‰˘ÌÂ˜ ·‰ÂÏÊ¤˜ (πππ:1, πππ:2), ÂÓÒ Â›ÛË˜ Î·Ú‰ÈÔ¿ıÂÈ· Ô˘ ‰ÂÓ ¤¯ÂÈ Ù·˘ÙÔÔÈËıÂ› ·Ó·Ê¤ÚÂÙ·È ÛÂ ‰‡Ô ·ÎfiÌ· Ì¤ÏË (π:4 Î·È ππ:3). ∏ ÌÂÙ¿ÏÏ·ÍË Ô˘ ‰È·ÈÛÙÒıËÎÂ ÛÙËÓ ·ÛıÂÓ‹-‰Â›ÎÙË ÌÂ ÙË ÛÙ¤ÓˆÛË ÓÂ˘ÌÔÓÈÎ‹˜ (πππ:1) ·ÊÔÚ¿ ÙÔ ÂÍfiÓÈÔ 3, ÂÓÒ ÛÂ ÚÔËÁÔ‡ÌÂÓÂ˜ ÌÂÏ¤ÙÂ˜ Ë ÛÙ¤ÓˆÛË ÙË˜ ÓÂ˘ÌÔÓÈÎ‹˜ ‚·Ï‚›‰·˜ Û˘Û¯ÂÙ›˙ÂÙ·È Û˘¯ÓfiÙÂÚ· ÌÂ ÌÂÙ·ÏÏ¿ÍÂÈ˜ ÛÙÔ ÂÍfiÓÈÔ 8 (3,8,11,12). ªÈ· ·ÎfiÌ· ÂÓ‰È·Ê¤ÚÔ˘Û· ·Ú·Ù‹ÚËÛË Â›Ó·È fiÙÈ ÂÓÒ fiÏ· Ù· Ì¤ÏË ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ ÌÂ ÙËÓ ÎÔÈÓ‹ ÌÂÙ¿ÏÏ·ÍË (·ÛıÂÓ‹˜-‰Â›ÎÙË˜, ÌËÙ¤Ú·, ÌËÙÚÈÎfi˜ ıÂ›Ô˜) ¤¯Ô˘Ó ÎÔÈÓ¿ ÌÔÚÊÔÏÔÁÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿, ÂÌÊ·Ó›˙Ô˘Ó ÂÓÙÔ‡ÙÔÈ˜ ÎÏÈÓÈÎ‹ ÂÙÂÚÔÁ¤ÓÂÈ·. ™˘ÁÎÂÎÚÈÌ¤Ó· Ë ÌËÙ¤Ú· (ππ:2) ‰ÂÓ ¤¯ÂÈ Û˘ÁÁÂÓ‹ Î·Ú‰ÈÔ¿ıÂÈ· fiˆ˜ Ù· ‰›‰˘Ì· ·È‰È¿ ÙË˜, ÂÓÒ ÛÙÔ ·ÙÔÌÈÎfi ÙË˜ ·Ó·ÌÓËÛÙÈÎfi ·Ó·Ê¤ÚÂÙ·È ÌfiÓÔ ·ÈÌÔÚÚ·ÁÈÎ‹ ‰È¿ıÂÛË. √ ‰Â ıÂ›Ô˜ ·fi ÙË ÌËÙ¤Ú· (ππ:3) ¤¯ÂÈ “Û˘ÛÙÔÏÈÎfi Ê‡ÛËÌ·” Î·È ÛÂ ·ÓÙ›ıÂÛË ÌÂ Ù· ˘fiÏÔÈ· ¿Û¯ÔÓÙ· Ì¤ÏË ÂÌÊ·Ó›˙ÂÈ Î·ÓÔÓÈÎfi ·Ó¿ÛÙËÌ·. ∏ ÂÓ‰ÔÔÈÎÔÁÂÓÂÈ·Î‹ ÔÈÎÈÏÔÌÔÚÊ›· ¤¯ÂÈ ·Ú·ÙËÚËıÂ› Î·È ÛÂ ¿ÏÏÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ÙË ÌÂÙ¿ÏÏ·ÍË A188G Î·È ·Ô‰›‰ÂÙ·È ÛÂ ÌÂÈˆÌ¤ÓË ‰ÈÂÈÛ‰˘ÙÈÎfiÙËÙ· ÙÔ˘ ÁÔÓÈ‰›Ô˘ ‹/Î·È ÛÂ Èı·Ó‹ Ú˘ıÌÈÛÙÈÎ‹ ‰Ú¿ÛË ¿ÏÏˆÓ (¿ÁÓˆÛÙˆÓ) ÁÔÓÈ‰›ˆÓ Î·È ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ (3,8,11,12). ŸÛÔÓ ·ÊÔÚ¿ ÙÔÓ Èı·Ófi ·ıÔÁÂÓÂÙÈÎfi ÚfiÏÔ ÙÔ˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ -21C→T ÛÙÔ ÂÛfiÓÈÔ 7 ÙÔ˘ ÁÔÓÈ‰›Ô˘ PTPN 11 Ô˘ ‰È·ÈÛÙÒıËÎÂ ÛÙËÓ ·ÛıÂÓ‹-‰Â›ÎÙË, ı· Ú¤ÂÈ Ó· ÂÎÙÈÌËıÂ› ÌfiÓÔ ·ÊÔ‡ ‰ÈÂÚÂ˘ÓËıÂ› ÛÂ ÌÂÁ·Ï‡ÙÂÚÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ ÌÂ NS Î·È ÌÂÙ¿ ·fi Û˘Û¯¤ÙÈÛË ÌÂ ÙÔÓ ˘ÁÈ‹ ÏËı˘ÛÌfi. ™‡ÓÙÔÌ· ı· ÍÂÎÈÓ‹ÛÂÈ Ô Î·Ù·Ú¯‹Ó ¤ÏÂÁ¯Ô˜ ÁÈ· ÙËÓ ·ÚÔ˘Û›· ‹ ÌË ÙÔ˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ ·˘ÙÔ‡ ÛÂ ‰Â›ÁÌ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 100 Ê˘ÛÈÔÏÔÁÈÎÒÓ ·ÙfiÌˆÓ ÚÔÎÂÈÌ¤ÓÔ˘ Ó· ÚÔÛ‰ÈÔÚÈÛıÂ›

ÙÔ ÔÛÔÛÙfi ÙË˜ ·ÚÔ˘Û›·˜ ·˘ÙÔ‡ ÙÔ˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ ÛÙÔÓ Ê˘ÛÈÔÏÔÁÈÎfi ÏËı˘ÛÌfi. ∏ Ê·ÈÓÔÙ˘ÈÎ‹ ÔÈÎÈÏÔÌÔÚÊ›· ÙÔ˘ NS ÂÈ‚¿ÏÏÂÈ ÙÔÓ ÌÔÚÈ·Îfi ÁÂÓÂÙÈÎfi ¤ÏÂÁ¯Ô ÙÔ˘ PTPN 11 ÛÂ fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ¿Ù˘Ô Ê·ÈÓfiÙ˘Ô Î·ıÒ˜ Î·È ÛÙÔ˘˜ Û˘ÁÁÂÓÂ›˜ 1Ô˘ ‚·ıÌÔ‡ ÁÈ· ÙËÓ ÂÈ‚Â‚·›ˆÛË ÙË˜ ÎÏÈÓÈÎ‹˜ ‰È¿ÁÓˆÛË˜ Î·È ÙË ÛˆÛÙ‹ Î·È ¤ÁÎ·ÈÚË ÁÂÓÂÙÈÎ‹ Î·ıÔ‰‹ÁËÛË.

µÈ‚ÏÈÔÁÚ·Ê›· 1. McKusick VA. Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders. 12th ed. Baltimore and London: The Johns Hopkins University Press; 1998, OMIM # 176876. Webpage: http://www.nlm.nih.gov/omim/ 2. Allanson JE. Noonan syndrome. In: Cassidy SB, Allanson JE, editors. Management of Genetic Syndromes. 2nd ed. Wiley Liss, Inc; 2005. p. 385. 3. Targaglia M, Kalidas K, Shaw A, Song X, Musat LD, van der Burgt I et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation and phenotypic heterogeneity. Am J Hum Genet 2002;70:1555-1563. 4. Noonan JA. Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease. Am J Dis Child 1968;116;373-380. 5. Noonan JA. Noonan syndrome revisited. J Pediatr 1999;135:667-668. 6. Jongmans M, Otten B, Noordam K, van der Burgt I. Genetics and variation in phenotype in Noonan syndrome. Horm Res 2004;62 (Suppl 3):S56-S59. 7. Marino B, Digilio MC, Toscano A, Giannotti A, Dallapiccola B. Congenital heart diseases in children with Noonan syndrome: An expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr 1999;135:703-706. 8. Sarkozy A, Conti E, Seripa D, Digilio MC, Grifone N, Tandoi C et al. Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes. J Med Genet 2003;40:704-708. 9. Jamieson CR, van der Burgt I, Brady AF, van Reen M, Elsawi MM, Hol F et al. Mapping a gene for Noonan syndrome to the long arm of chromosome 12. Nat Genet 1994;8:357-360. 10. Tamir I, Dal Porto JM, Cambier JC. Cytoplasmic protein tyrosine phosphatase SHP-1 and SHP-2: regulators of B cell signal transduction. Curr Opin Immunol 2000;12:307-315. 11. Yoshida R, Hasegawa T, Hasegawa Y, Nagai T, Kinoshita E, Tanaka Y et al. Protein-tyrosine phosphatase, nonreceptor type II mutation analysis and clinical assessment in 45 patients with Noonan syndrome. J Clin Endocrinol Metab 2004;89:3359-3364. 12. Bertola DR, Pereira CA, de Oliveira PSL, Kim CA, Krieger JE. Clinical variability in a Noonan syndrome family with a new PTPN11 gene mutation. Am J Med Genet 2004;130A:378-383. ¶·È‰È·ÙÚÈÎ‹ 2006;69:447-451

452

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CASE REPORT

∞ÓÙÈÌÂÙÒÈÛË ÙË˜ ÔÛÙÂÔfiÚˆÛË˜ Î·È ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ ÌÂ ‰ÈÓ·ÙÚÈÔ‡¯Ô ·ÌÈ‰ÚÔÓ¿ÙË ÛÂ ‚Ú¤ÊÔ˜ ÌÂ ·ÙÂÏ‹ ÔÛÙÂÔÁ¤ÓÂÛË Ù‡Ô˘ IV 1 ∞’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó· 2 √ÌfiÙÈÌÔ˜ ∫·ıËÁËÙ‹˜ ¶·È‰È·ÙÚÈÎ‹˜ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ 3 ¢ÈÂ‡ı˘ÓÛË °ÂÓÂÙÈÎ‹˜, πÓÛÙÈÙÔ‡ÙÔ ÀÁÂ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó· 4 µÈÔ¯ËÌÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ¶. ¢. §··ÙÛ¿ÓË˜ ∞ÛÎÏËÈÔ‡ 44 ∆.∫. 114 71, ∞ı‹Ó· ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 23-02-2006 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 18-07-2006

ª. ¶··Ê˘Ï·ÎÙÔ‡1, ¶. §··ÙÛ¿ÓË˜2, ¶. ¶Ô˘ÏﬁÔ˘ÏÔ˜1, M. B. Petersen3, ∫. ªÈ¯·Ï·Î¿ÎÔ˘4, ∫. ¶ÚÔ‡ÓÙ˙Ô˘ - ∫·ÛÛÈÔ‡1

¶ÂÚ›ÏË„Ë: ∏ ·ÙÂÏ‹˜ ÔÛÙÂÔÁ¤ÓÂÛË (∞√) ·ÔÙÂÏÂ› ÂÙÂÚÔÁÂÓ‹ ÁÂÓÂÙÈÎ‹ ‰È·Ù·Ú·¯‹ ÌÂ ·˘ÍËÌ¤ÓË Â˘ıÚ·˘ÛÙfiÙËÙ· ÙˆÓ ÔÛÙÒÓ, ÔÛÙÂÔfiÚˆÛË Î·È ÂÎ‰ËÏÒÛÂÈ˜ ·fi ¿ÏÏÔ˘˜ Û˘Ó‰ÂÙÈÎÔ‡˜ ÈÛÙÔ‡˜. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÂÚ›ÙˆÛË ‚Ú¤ÊÔ˘˜ ËÏÈÎ›·˜ ÔÎÙÒ ÌËÓÒÓ, ÙÔ ÔÔ›Ô ·ÚÔ˘Û›·ÛÂ ÙÚ›· Î·Ù¿ÁÌ·Ù· ÙˆÓ ÔÛÙÒÓ, ÔÛÙÂÔfiÚˆÛË Î·È Î·ı›˙ËÛË ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ ÙË˜ ÔÛÊ˘˚Î‹˜ ÌÔ›Ú·˜. ∞ÔÊ·Û›ÛÙËÎÂ Ë ÂÓ‰ÔÊÏ¤‚È· ıÂÚ·Â›· ÌÂ ‰ÈÓ·ÙÚÈÔ‡¯Ô ·ÌÈ‰ÚÔÓ¿ÙË Î·È ÌÂ ‰ÔÛÔÏÔÁÈÎfi Û¯‹Ì· 0,5-1,5 mg/kg ËÌÂÚËÛ›ˆ˜ ÁÈ· ‰‡Ô ËÌ¤ÚÂ˜, Î¿ıÂ 6-12 Â‚‰ÔÌ¿‰Â˜. ™ÙËÓ ÚÒÙË Û˘ÓÂ‰Ú›·, ÙÔ ‚Ú¤ÊÔ˜ ·ÚÔ˘Û›·ÛÂ ˘ÚÂÙfi 39,5oC Î·È Ô˘‰ÂÙÂÚÔÂÓ›·, ÁÈ· ‚Ú·¯‡ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·. ∂›ÛË˜, ·Ú·ÙËÚ‹ıËÎÂ ÂÏ¿ÙÙˆÛË ÙË˜ Û˘ÁÎ¤ÓÙÚˆÛË˜ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ (Ca++) ÛÙÔÓ ÔÚfi Î·È ·‡ÍËÛË ÙË˜ ·Ú·ıÔÚÌfiÓË˜ (PTH). ∆· ÎÏÈÓÈÎ¿ Û˘ÌÙÒÌ·Ù· ÙË˜ ÏÔ›ÌˆÍË˜ Ô˘ ÌÔÈ¿˙Ô˘Ó ÌÂ ÈÔÁÂÓ‹ Û˘Ó‰ÚÔÌ‹ Î·È ÔÈ ‚ÈÔ¯ËÌÈÎ¤˜ ‰È·Ù·Ú·¯¤˜ ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙÔ˘˜ ÂfiÌÂÓÔ˘˜ Î‡ÎÏÔ˘˜ ıÂÚ·Â›·˜, ÂÎÙfi˜ ·fi ÙËÓ fiÁ‰ÔË ¤Á¯˘ÛË, Î·Ù¿ ÙËÓ ÔÔ›· ‚Ú¤ıËÎÂ ÌÈÎÚ‹ ·‡ÍËÛË ÙË˜ PTH. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ıÂÚ·Â›·˜, Ô ·ÚÈıÌfi˜ ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ ÌÂÈÒıËÎÂ. ∏ Ï¿ÁÈ· ·ÎÙÈÓÔÁÚ·Ê›· (·/·) ÔÛÊ˘˚Î‹˜ ÌÔ›Ú·˜ ÛÔÓ‰˘ÏÈÎ‹˜ ÛÙ‹ÏË˜ (√ª™™) ¤‰ÂÈÍÂ ÙËÓ Â·ÓfiÚıˆÛË ÙÔ˘ ‡„Ô˘˜ ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ Î·È ÙË˜ ÔÛÙÂÔfiÚˆÛË˜. ∏ ÓfiÛÔ˜ ÙÔ˘ ‚Ú¤ÊÔ˘˜ Ù·ÍÈÓÔÌ‹ıËÎÂ ÛÙÔÓ Ù‡Ô IV ÌÂ ¯·ÌËÏfi ·Ó¿ÛÙËÌ·. ∆Ô Ì‹ÎÔ˜ ÛÒÌ·ÙÔ˜ (ª™) ‚Ú¤ıËÎÂ 67 cm, ÛÙË 10Ë ÂÎ·ÙÔÛÙÈ·›· ı¤ÛË (∂£) ÙË˜ Î·Ì‡ÏË˜ ·Ó¿Ù˘ÍË˜ ÛÙËÓ ËÏÈÎ›· ÙˆÓ 8 ÌËÓÒÓ Î·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ıÂÚ·Â›·˜, ÛÂ ËÏÈÎ›· 26 ÌËÓÒÓ, ÌÈÎÚfiÙÂÚÔ ·fi ÙËÓ ÙÚ›ÙË ∂£ (ª™: 81 cm). ∂ÔÌ¤Óˆ˜, Ë ‰ÈÓ·ÙÚÈÔ‡¯Ô˜ ·ÌÈ‰ÚÔÓ¿ÙË ‰ÂÓ Â›¯Â Â˘ÓÔ˚Î‹ Â›‰Ú·ÛË ÛÙÔ ·Ó¿ÛÙËÌ· ÙÔ˘ ·ÛıÂÓ‹. ™˘ÛÙ‹ıËÎÂ Ë ÙÔÔı¤ÙËÛË ÂÓ‰ÔÌ˘ÂÏÈÎÔ‡ ‹ÏÔ˘ ÛÙ· ÌËÚÈ·›· ÔÛÙ¿ ÁÈ· ÙË ‚ÂÏÙ›ˆÛË ÙË˜ ‚¿‰ÈÛË˜ Î·È ÙË˜ ÈÛÔÚÚÔ›·˜. ∏ ·/· ·ÚÈÛÙÂÚÔ‡ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡ ¤‰ÂÈÍÂ ÙËÓ ÂÌÊ¿ÓÈÛË ÏÂ˘ÎÒÓ ÂÚÈÔ¯ÒÓ ÛÙËÓ Â›Ê˘ÛË, ÌÂÙ¿ ·fi ÙË ıÂÚ·Â›· 18 ÌËÓÒÓ. ™˘ÌÂÚ·ÛÌ·ÙÈÎ¿, Ë ‰ÈÓ·ÙÚÈÔ‡¯Ô˜ ·ÌÈ‰ÚÔÓ¿ÙË ‰ÂÓ ¤¯ÂÈ Â›‰Ú·ÛË ÛÙË Ê˘ÛÈÎ‹ ÔÚÂ›· ÙË˜ ∞√, ·ÏÏ¿ Â›Ó·È Ë ÌÔÓ·‰ÈÎ‹ Ê·ÚÌ·ÎÂ˘ÙÈÎ‹ ıÂÚ·Â›· ÚÔÎÂÈÌ¤ÓÔ˘ Ó· ÂÈÙÂ˘¯ıÂ› Ë Î·Ï‡ÙÂÚË Û˘ÌÙˆÌ·ÙÈÎ‹ ‚ÂÏÙ›ˆÛË ÙË˜ ÓfiÛÔ˘. §¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ∞ÙÂÏ‹˜ ÔÛÙÂÔÁ¤ÓÂÛË, Î·Ù¿ÁÌ·Ù·, ·ÌÈ‰ÚÔÓ¿ÙË.

Symptomatic pamidronate treatment of an infant with osteogenesis imperfecta type IV 1 1st Paediatric Clinic, “Aghia Sophia” Children’s Hospital, Athens 2 Emeritus Professor of Paediatrics, University of Ioannina 3 Department of Genetics, Institute of Child Health, ”Aghia Sophia” Children’s Hospital, Athens 4 Biochemical Department, “Aghia Sophia” Children’s Hospital, Athens Correspondence: P. D. Lapatsanis 44, Asklepiou Str. 114 71, Athens Date of submission: 23-02-2006 Date of approval: 18-07-2006

¶·È‰È·ÙÚÈÎ‹ 2006;69:452-457

M. Papaphylactou1, P. Lapatsanis2, P. Poulopoulos1, M. B. Petersen3, K. Michalakakou4, K. Prountzou - Kassiou1

Abstract: Osteogenesis imperfecta (√π) is a heterogenous genetic disorder with increased bone fragility, osteoporosis and other connective tissue manifestations. The case is described of an 8 month-old infant who had three fractures, osteoporosis and collapsed vertebral bodies of the lumbar spine. It was decided to administer treatment with intravenous pamidronate in doses of 0.5-1.5 mg/kg/day for two days, every 6-12 weeks. On the first infusion the infant developed a fever of 39.5oC and neutropenia for a short period of time. Reduction in the serum concentration of calcium and an increase of parathyroid hormone were observed. The clinical symptoms of a flu-like syndrome and the biochemical disturbances were observed only on the first infusion, and on the eighth infusion a small increase in serum parathyroid hormone was again found. Following treatment the number of fractures diminished and X-ray of the spine revealed restoration of vertebral height and improvement of osteoporosis. The infant’s disease is classified as OI type IV with short stature. His length was 67 cm (10th centile) at the age of 8 months and 81 cm (<3rd centile) at the age of 26 months, showing that the pamidronate had no beneficial effect on the length of the child. It was suggested to place nails

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∞ÙÂÏ‹˜ ÔÛÙÂÔÁ¤ÓÂÛË Î·È ·ÌÈ‰ÚÔÓ¿ÙË

in the femurs to improve ambulatory status. X-ray of the left femur showed the appearance of a white area in the epiphysis after 18 months of treatment. It was concluded that pamidronate did not affect the natural course of the disease, but it is the only medical treatment available to provide the best symptomatic improvement of OI.

Key words: Osteogenesis imperfecta, fractures, pamidronate.

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ ∞√ µ™ ª™ ¶∫ ∂£ √ª™™ Ca++ WBC PTH 25-√∏-D ·/·

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∂ÈÛ·ÁˆÁ‹ ∆Ô ·ÓıÚÒÈÓÔ ÛÒÌ· ·ÔÙÂÏÂ›Ù·È ·fi ÂÚÂÈÛÙÈÎÔ‡˜ Î·È Ì·Ï·ÎÔ‡˜ ÈÛÙÔ‡˜. √ ÂÚÂÈÛÙÈÎfi˜ ÈÛÙfi˜ Â›Ó·È ·Ôı‹ÎË ÌÂÙ¿ÏÏˆÓ Î·È Û˘ÓÙÂÏÂ› ÛÙÔÓ ‚ÈÔÛÙ·ÙÈÎfi ÌË¯·ÓÈÛÌfi. ∆· ÔÛÙ¿ ÚÔÛÊ¤ÚÔ˘Ó ÚÔÊ‡Ï·ÍË, ‚ÈÔÛÙ·ÙÈÎÔ‡˜ ÌË¯·ÓÈÛÌÔ‡˜ Î·È ·ÔÙÂÏÔ‡Ó ÙÔ ·ÁÎ˘ÚÔ‚fiÏÈÔ ÙˆÓ Ì˘ÒÓ ÁÈ· ÙÔÓ Â˘ıÂÈ·ÛÌfi, ÙË ı¤ÛË Î·È ÙËÓ Î›ÓËÛË. ªÂ ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘, Ù· ÔÛÙ¿ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·ÒÏÂÈ· ÙË˜ ÔÛÙÈÎ‹˜ Ì¿˙·˜ Î·È ÙË˜ ·ÓıÂÎÙÈÎfiÙËÙ·˜, ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÌÊ¿ÓÈÛË Î·Ù·ÁÌ¿ÙˆÓ, ÙË ÌÂ›ˆÛË ÙË˜ ÎÈÓËÙÈÎfiÙËÙ·˜ Î·È ¯ÚfiÓÈ· ¿ÏÁË. ∞˘Ù‹ Ë ÎÏÈÓÈÎ‹ ÂÈÎfiÓ·, ˆÛÙfiÛÔ, ‰ÂÓ ·Ó·Ì¤ÓÂÙ·È ÛÂ ÓÂÔÁÓfi ‹ ‚Ú¤ÊÔ˜. ŸÙ·Ó ·ÚÔ˘ÛÈ·ÛÙÂ› Ù¤ÙÔÈ· Î·Ù¿ÛÙ·ÛË, ÌÔÚÂ› Ó· ÙÂıÂ› ˘Ô„›· ‚ÚÂÊÈÎ‹˜ Î·ÎÔÔ›ËÛË˜ Î·È Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ‰È·ÎÚÈıÂ› ·fi ÙËÓ ·ÙÂÏ‹ ÔÛÙÂÔÁ¤ÓÂÛË (∞√) (1). ∏ ∞√ ·ÔÙÂÏÂ› ÂÙÂÚÔÁÂÓ‹ ÁÂÓÂÙÈÎ‹ ‰È·Ù·Ú·¯‹, Ë ÔÔ›· ÔÊÂ›ÏÂÙ·È Î˘Ú›ˆ˜ ÛÂ ÌÂÙ·ÏÏ¿ÍÂÈ˜ ÛÙ· ÁÔÓ›‰È· COL1A1 ‹ COL1A2 Ô˘ Îˆ‰ÈÎÔÔÈÔ‡Ó ÙÈ˜ · ·Ï˘Û›‰Â˜ ÙÔ˘ ÎÔÏÏ·ÁfiÓÔ˘ Ù‡Ô˘ I. ™˘ÓÈÛÙ¿Ù·È Ê˘ÛÈÔıÂÚ·Â›·, ‰ÈÔÚıˆÙÈÎ¤˜ ÂÂÌ‚¿ÛÂÈ˜ ÙˆÓ ·Ú·ÌÔÚÊÒÛÂˆÓ ÙˆÓ Ì·ÎÚÒÓ ÔÛÙÒÓ Î·È ¤ÏÂÁ¯Ô˜ ÙˆÓ ÔÛÙÈÎÒÓ ·ÏÁÒÓ. ∏ È·ÙÚÈÎ‹ ·‰˘Ó·ÙÂ› Ó· ÚÔÛÊ¤ÚÂÈ ›·ÛË ÙË˜ ÓfiÛÔ˘. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÔÚÂ›· Î·È Ë ·ÓÙÈÌÂÙÒÈÛË ‚Ú¤ÊÔ˘˜, Ô˘ ˘Ô‚Ï‹ıËÎÂ ÛÂ ıÂÚ·Â›· ÌÂ ‰ÈÓ·ÙÚÈÔ‡¯Ô ·ÌÈ‰ÚÔÓ¿ÙË.

¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛË˜ ¶ÚfiÎÂÈÙ·È ÁÈ· ·ÁfiÚÈ ËÏÈÎ›·˜ 8 ÌËÓÒÓ Ô˘ ÂÈÛ‹¯ıË ÛÙËÓ ÎÏÈÓÈÎ‹ ÌÂ Î·Ù¿ÁÌ·Ù· ·fi ÙÈ˜ ÚÒÙÂ˜ Â‚‰ÔÌ¿‰Â˜ ÙË˜ ˙ˆ‹˜ ÙÔ˘. ∆Ô ÚÒÙÔ Î¿Ù·ÁÌ· ·ÚÔ˘ÛÈ¿ÛÙËÎÂ ÛÙËÓ ËÏÈÎ›· ÙˆÓ ÙÂÛÛ¿ÚˆÓ Â‚‰ÔÌ¿‰ˆÓ, Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ Û›ÙÈÛË˜, ÛÙÔ ·ÚÈÛÙÂÚfi ‚Ú·¯ÈfiÓÈÔ ÔÛÙfi, ÌÂ Ô›‰ËÌ· Î·È ÂÚÈÔÚÈÛÌfi ÙË˜ ÎÈÓËÙÈÎfiÙËÙ·˜. ∆Ô ‰Â‡ÙÂÚÔ Î¿Ù·ÁÌ· ·ÚÔ˘ÛÈ¿ÛÙËÎÂ, ÛÂ ËÏÈÎ›· 3 ÌËÓÒÓ, ÛÙÔ ‰ÂÍÈfi ÌËÚÈ·›Ô ÔÛÙfi Î·Ù¿ ÙËÓ ·ÏÏ·Á‹ ÙË˜ ¿Ó·˜ (∂ÈÎfiÓ· 1·, ‚). ™Â ËÏÈÎ›· 5 ÌËÓÒÓ ÂÈÛ‹¯ıË ÛÂ ¶·ÓÂÈÛÙËÌÈ·Î‹ ∫ÏÈÓÈÎ‹ ÙË˜ £ÂÛÛ·ÏÔÓ›ÎË˜ ÁÈ· ‰ÈÂÚÂ‡ÓËÛË Î·È ÌÂÙ¿ ·fi ÙÚÂÈ˜ ËÌ¤ÚÂ˜ ‰È·ÁÓÒÛÙËÎÂ ∞√. ™Â ËÏÈÎ›· 7 ÌËÓÒÓ ·ÚÔ˘Û›·ÛÂ Ó¤Ô Î¿Ù·ÁÌ· ÛÙÔ ·ÚÈÛÙÂÚfi ÌËÚÈ·›Ô ÔÛÙfi. ™ÙÔÓ fiÁ‰ÔÔ Ì‹Ó· ·ÚÔ˘Û›·ÛÂ ¤Î‰ËÏË ˘ÔÎÈÓËÙÈÎfiÙËÙ· ÙÔ˘ ‰ÂÍÈÔ‡ ÌËÚÈ·›Ô˘ ¿ÎÚÔ˘. ∞ÎÙÈÓÔÏÔÁÈÎ¿ ‰ÂÓ ·Ú·ÙËÚ‹ıËÎÂ Î¿Ù·ÁÌ·, ·ÏÏ¿ Ú·È‚fi Û¯‹Ì· ÌËÚÈ·›ˆÓ ÔÛÙÒÓ. ∫·Ù¿ ÙË Ê˘ÛÈÎ‹ ÂÍ¤Ù·ÛË ‰È·ÈÛÙÒıËÎ·Ó ÏÂ˘ÎfiÊ·ÈË ·fi¯ÚˆÛË ÛÎÏËÚÔ‡ ¯ÈÙÒÓ· ÔÊı·ÏÌÒÓ, ÌÂÁ¿ÏË ÚfiÛıÈ· ËÁ‹, ¤Ó· ‰fiÓÙÈ ÛÙËÓ Î¿Ùˆ ÁÓ¿ıÔ Î·È ÌÔÁÁÔÏÔÂÈ‰‹˜ ÎËÏ›‰· ÛÙËÓ ÔÛÊ˘Ô˚ÂÚ¿ ¯ÒÚ·. ∞fi Ù· ¿ÏÏ· Û˘ÛÙ‹Ì·Ù· ‰ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ·ıÔÏÔÁÈÎ¿ Â˘Ú‹Ì·Ù·. ∆· ÛˆÌ·ÙÔÌÂÙÚÈÎ¿ ÛÙÔÈ¯Â›· ‹Ù·Ó Ù· ·ÎfiÏÔ˘ı·: ‚¿ÚÔ˜ ÛÒÌ·ÙÔ˜ (µ™): 7560 g (3Ë-10Ë ∂£), ª™: 67,5 cm (10Ë ∂£) Î·È ÂÚ›ÌÂÙÚÔ˜ ÎÂÊ·Ï‹˜ (¶∫): 46 cm (95Ë ∂£). √ ·ÈÌ·ÙÔÏÔÁÈÎfi˜ Î·È ‚ÈÔ¯ËÌÈÎfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍÂ Ê˘ÛÈÔÏÔÁÈÎ¤˜ ÙÈÌ¤˜ ‰ÂÈÎÙÒÓ ÛÙÔ ·›Ì·. ™ÙËÓ Ï¿ÁÈ· ·/· √ª™™ ÚÈÓ ÙË ıÂÚ·Â›·, ·Ú·ÙËÚ‹ıËÎÂ ¤Î‰ËÏË ÔÛÙÂÔfiÚˆÛË, ÎÔ›Ï·ÓÛË ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ Î·È ÌÂÁ¿Ï· ÌÂÛÔÛÔÓ‰‡ÏÈ· ‰È·ÛÙ‹Ì·Ù· (∂ÈÎfiÓ· 2·). ∞ÔÊ·Û›ÛÙËÎÂ ¤Ó·ÚÍË ıÂÚ·Â›·˜ ÌÂ ÂÓ‰ÔÊÏ¤‚È· ¯ÔÚ‹ÁËÛË ‰ÈÓ·ÙÚÈÔ‡¯Ô˘ ·ÌÈ‰ÚÔÓ¿ÙË˜ ÛÂ ‰fiÛË 0,5 mg/kg ËÌÂÚËÛ›ˆ˜ ÁÈ· ‰‡Ô ËÌ¤ÚÂ˜. √È Û˘ÓÂ‰Ú›Â˜ Â·Ó·Ï·Ì‚¿ÓÔÓÙ·Ó Î¿ıÂ 6-12 Â‚‰ÔÌ¿‰Â˜ Î·È Ë ‰fiÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î˘Ì¿ÓıËÎÂ ·fi 0,5 ¤ˆ˜ 1,5 mg/kg ËÌÂÚËÛ›ˆ˜ (∂ÈÎfiÓ· 3). ¶·È‰È·ÙÚÈÎ‹ 2006;69:452-457

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‚ ‚

∂ÈÎfiÓ· 1. ·) ∫¿Ù·ÁÌ· ·ÚÈÛÙÂÚÔ‡ ‚Ú·¯ÈfiÓÈÔ˘ ÔÛÙÔ‡. ‚) √ÛÙÂÔfiÚˆÛË ÌÂ Î¿Ù·ÁÌ· ‰ÂÍÈÔ‡ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡.

Ÿˆ˜ Ê·›ÓÂÙ·È Î·È ·fi ÙË Û¯ËÌ·ÙÈÎ‹ ·Ú¿ÛÙ·ÛË, ÛÙËÓ ÚÒÙË Û˘ÓÂ‰Ú›· ·ÚÔ˘Û›·ÛÂ ÌÂ›ˆÛË ÙˆÓ ÙÈÌÒÓ ÙÔ˘ Ca++ ÛÙÔÓ ÔÚfi Î·È ·‡ÍËÛË ÙË˜ PTH, Ô˘ ·Ô‰fiıËÎÂ ÛÙËÓ ÎÈÓËÙÔÔ›ËÛË ·Û‚ÂÛÙ›Ô˘ ·fi ÙÔ˘˜ Ì·Ï·ÎÔ‡˜ ÈÛÙÔ‡˜ ÛÙ· ¶·È‰È·ÙÚÈÎ‹ 2006;69:452-457

∂ÈÎfiÓ· 2. ·) ∏ Ï¿ÁÈ· ·/· √ª™™, ÚÈÓ ÙËÓ ¤Ó·ÚÍË ÙË˜ ıÂÚ·Â›·˜, ‰Â›¯ÓÂÈ ¤Î‰ËÏË ÔÛÙÂÔfiÚˆÛË ÌÂ Î·ı›˙ËÛË ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ. ‚) ªÂÙ¿ ·fi 12 Ì‹ÓÂ˜ ıÂÚ·Â›·˜ ÌÂ ‰ÈÓ·ÙÚÈÔ‡¯Ô ·ÌÈ‰ÚÔÓ¿ÙË, Ê·›ÓÂÙ·È ·‡ÍËÛË ÙÔ˘ ÌÂÁ¤ıÔ˘˜ ÙˆÓ ÛˆÌ¿ÙˆÓ ÙˆÓ ÛÔÓ‰‡ÏˆÓ Î·È ÌÂ›ˆÛË ÙˆÓ Â˘ÚËÌ¿ÙˆÓ ÙË˜ ÔÛÙÂÔfiÚˆÛË˜.

455

∞ÙÂÏ‹˜ ÔÛÙÂÔÁ¤ÓÂÛË Î·È ·ÌÈ‰ÚÔÓ¿ÙË

2004

Ca ÔÚÔ‡ mg/dl

ª‹ÎÔ˜ ÛÒÌ·ÙÔ˜ cm

¢ÈÓ·ÙÚÈÔ‡¯Ô˜ ª¿ÈÔ˜ πÔ‡ÓÈÔ˜ ∞‡ÁÔ˘ÛÙÔ˜ ¶·ÌÈ‰ÚÔÓ¿ÙË 0,5 x 2 ËÌ. 0,75 x 2 ËÌ. 1,0 x 2 ËÌ. 81 79 77 75 73 10Ë ∂£ 71 69 10Ë ∂£ 67

2005 √ÎÙÒ‚ÚÈÔ˜ 1,25 x 2 ËÌ.

π·ÓÔ˘¿ÚÈÔ˜ ∞Ú›ÏÈÔ˜ 1,5 x 2 ËÌ. 1,0 x 3 ËÌ.

πÔ‡ÏÈÔ˜ ™ÂÙ¤Ì‚ÚÈÔ˜ 1,0 x 3 ËÌ. 1,15 x 2 ËÌ. <3Ë ∂£ <3Ë ∂£

<3Ë∂£ <3Ë ∂£ 3Ë ∂£

<3Ë ∂£

11 10 9 8

PTH pg/ml

100 70

HÏÈÎ›· ÛÂ Ì‹ÓÂ˜

∂ÈÎfiÓ· 3. ∞ÂÈÎÔÓ›˙ÂÙ·È ÙÔ ‰ÔÛÔÏÔÁÈÎfi Û¯‹Ì· ÙË˜ ÂÓ‰ÔÊÏ¤‚È·˜ ¯ÔÚ‹ÁËÛË˜ ‰ÈÓ·ÙÚÈÔ‡¯Ô˘ ·ÌÈ‰ÚÔÓ¿ÙË˜, ÙÔ ª™, Ë Û˘ÁÎ¤ÓÙÚˆÛË Ca++ Î·È PTH ÛÙÔÓ ÔÚfi Î·È Ë ËÏÈÎ›· ÙÔ˘ ·ÛıÂÓ‹, ÛÙÔ˘˜ ·ÓÙ›ÛÙÔÈ¯Ô˘˜ Î‡ÎÏÔ˘˜ ıÂÚ·Â›·˜.

ÔÛÙ¿. ÕÚ¯ÈÛÂ Û˘ÛÙËÌ·ÙÈÎ‹ ¯ÔÚ‹ÁËÛË ‚ÈÙ·Ì›ÓË˜ D (10 Ìg ËÌÂÚËÛ›ˆ˜), ·Ú¿ Ù· Ê˘ÛÈÔÏÔÁÈÎ¿ Â›Â‰· ÙË˜ 25-˘‰ÚÔÍ˘-‚ÈÙ·Ì›ÓË˜ D (25√∏-D) ÛÂ ‰‡Ô ÌÂÙÚ‹ÛÂÈ˜ (23 Î·È 25 ng/ml). º˘ÛÈÔÏÔÁÈÎ‹ Û˘ÁÎ¤ÓÙÚˆÛË Ca++ ÔÚÔ‡, ·ÏÏ¿ ÌÈÎÚ‹ ·‡ÍËÛË ÙÔ˘ ÂÈ¤‰Ô˘ ÙË˜ PTH, ‚Ú¤ıËÎÂ Î·È ÛÙËÓ fiÁ‰ÔË Û˘ÓÂ‰Ú›·, ÛÂ ËÏÈÎ›· 26 ÌËÓÒÓ (™ÂÙ¤Ì‚ÚÈÔ˜ 2005). ∆Ë ‰Â‡ÙÂÚË ËÌ¤Ú· ÌÂÙ¿ ÙËÓ ÚÒÙË ¤Á¯˘ÛË, Ô ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·ÛÂ ˘ÚÂÙfi 39,5ÔC, Ô˘ ˘Ô¯ÒÚËÛÂ ÛÂ 48 ÒÚÂ˜. ∆· ·ÈÌ·ÙÔÏÔÁÈÎ¿ ·ÔÙÂÏ¤ÛÌ·Ù· ÌÂÙ¿ ÙËÓ ÚÒÙË Û˘ÓÂ‰Ú›· ‹Ù·Ó Ù· ·ÎfiÏÔ˘ı·: ÏÂ˘Î¿ ·ÈÌÔÛÊ·›ÚÈ· (WBC): 3300/mm3 [ÔÏ˘ÌÔÚÊÔ‡ÚËÓ· (¶): 4%, ÏÂÌÊÔÎ‡ÙÙ·Ú· (§): 84%, ÌÔÓÔ‡ÚËÓ· (ª): 7%], ·fiÏ˘ÙÔ˜ ·ÚÈıÌfi˜ ¶: 132/mm3. ∂·Ó¿ÏË„Ë ÙË˜ ÁÂÓÈÎ‹˜ ·›Ì·ÙÔ˜ ÛÂ ‰¤Î· ËÌ¤ÚÂ˜ ¤‰ÂÈÍÂ: WBC: 8500/mm3 (¶: 15%, §: 74%, ª: 7%), ·fiÏ˘ÙÔ˜ ·ÚÈıÌfi˜ ¶: 1275/mm3. ∏ ·Ó¿Ï˘ÛË ÙˆÓ ÈÓÔ‚Ï·ÛÙÒÓ Î·È Ë cDNA ·Ó¿Ï˘ÛË ÙˆÓ COL1A1 (51 ÂÍÒÓÈ·) Î·È COL1A2 (52 ÂÍÒÓÈ·) ÁÔÓÈ‰›ˆÓ, ¤‰ÂÈÍÂ ÌÂÙ¿ÏÏ·ÍË ÛÙÔ ÂÍÒÓÈÔ 37 ÙÔ˘ ÁÔÓÈ‰›Ô˘ COL1A1. ∏ ÌÂÙ¿ÏÏ·ÍË ·˘Ù‹ ÚÔÎ‡ÙÂÈ ÌÂ ·ÓÙÈÎ·Ù¿ÛÙ·ÛË ÙË˜ ÁÏ˘Î›ÓË˜ ·fi ÙË ÛÂÚ›ÓË ÛÙË ı¤ÛË p.643 ÙÔ˘ ÁÔÓÈ‰›Ô˘ COL1A1 (p.Gly643Ser). ∆Ô ·ÔÙ¤ÏÂÛÌ· ·˘Ùfi ÂÈ‚Â‚·›ˆÛÂ Ù· ÎÏÈÓÈÎ¿ Î·È ‚ÈÔ¯ËÌÈÎ¿ Â˘Ú‹Ì·Ù· ÙË˜ ÓfiÛÔ˘ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È. ∆· ÎÏÈÓÈÎ¿, ‚ÈÔ¯ËÌÈÎ¿ Î·È ÌÔÚÈ·Î¿ Â˘Ú‹Ì·Ù· Â›Ó·È Û˘Ì‚·Ù¿ ÌÂ ÙÔÓ Ù‡Ô IV ÙË˜ ∞√.

∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ıÂÚ·Â›·˜, ÙÔ ‚Ú¤ÊÔ˜ ‰ÂÓ ·ÚÔ˘Û›·˙Â ¿ÏÁË Î·È Ô ‡ÓÔ˜ ÙÔ˘ ‹Ù·Ó ÈÔ ‹ÚÂÌÔ˜ ÛÂ Û¯¤ÛË ÌÂ ÙÔ ‰È¿ÛÙËÌ· ÚÈÓ ÙË ıÂÚ·Â›·, Û‡ÌÊˆÓ· ÌÂ ÙËÓ ¿Ô„Ë ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘. ªÂÙ¿ ÙËÓ ¤Ó·ÚÍË ÙË˜ ıÂÚ·Â›·˜, ·ÚÔ˘Û›·ÛÂ ‰‡Ô Î·Ù¿ÁÌ·Ù· - ÛÙËÓ ËÏÈÎ›· ÙˆÓ 16 Î·È 19 ÌËÓÒÓ - Î·Ù¿ ÙË ‚¿‰ÈÛË, ÛÙÔ ¿Óˆ ÙÚÈÙËÌfiÚÈÔ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡, fiÔ˘ Î·È ÙÔ Î¿Ù·ÁÌ· ÛÙËÓ ËÏÈÎ›· ÙˆÓ 7 ÌËÓÒÓ. ¢Ò‰ÂÎ· Ì‹ÓÂ˜ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË ÙË˜ ıÂÚ·Â›·˜, Ë Ï¿ÁÈ· ·/· √ª™™ ¤‰ÂÈÍÂ fiÙÈ ·ÔÎ·Ù·ÛÙ¿ıËÎÂ ÙÔ ‡„Ô˜ ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ, ÌÂ Û·Ê‹ ÌÂ›ˆÛË ÙˆÓ ÔÛÙÂÔÚˆÙÈÎÒÓ ·ÏÏÔÈÒÛÂˆÓ (∂ÈÎfiÓ· 2‚). ™ÙËÓ ËÏÈÎ›· ÙˆÓ 26 ÌËÓÒÓ Û˘ÛÙ‹ıËÎÂ Ë ÙÔÔı¤ÙËÛË ÂÓ‰ÔÌ˘ÂÏÈÎÔ‡ ‹ÏÔ˘ ÛÙ· ÌËÚÈ·›· ÔÛÙ¿, ÏfiÁˆ ·Ú·ÌfiÚÊˆÛ‹˜ ÙÔ˘˜ (∂ÈÎfiÓ· 4). ™ÙËÓ ·/· ·Ú·ÙËÚ‹ıËÎ·Ó ÏÂ˘Î¤˜ Ù·ÈÓ›Â˜ ÛÙËÓ Â›Ê˘ÛË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡.

™˘˙‹ÙËÛË ∏ ·ÓÙÈÌÂÙÒÈÛË ÙË˜ ∞√ ÌÂ ÂÓ‰ÔÊÏ¤‚È· ¯ÔÚ‹ÁËÛË ‰ÈÓ·ÙÚÈÔ‡¯Ô˘ ·ÌÈ‰ÚÔÓ¿ÙË˜ Û˘ÓÈÛÙ¿Ù·È ·fi ÙË ‚È‚ÏÈÔÁÚ·Ê›· (2-4). ŒÏÏËÓÂ˜ Û˘ÁÁÚ·ÊÂ›˜ (4) ·Ó·ÎÔ›ÓˆÛ·Ó ÂÚ›ÙˆÛË ÓÂÔÁÓÔ‡ ÌÂ ∞√, ÛÙÔ ÔÔ›Ô ¯ÔÚËÁ‹ıËÎÂ ‰ÈÓ·ÙÚÈÔ‡¯Ô˜ ·ÌÈ‰ÚÔÓ¿ÙË, ·ÏÏ¿ ‰ÂÓ ÙË ‰ËÌÔÛ›Â˘Û·Ó ÛÂ È·ÙÚÈÎfi ÂÚÈÔ‰ÈÎfi Î·È ‰ÂÓ ˘¿Ú¯Ô˘Ó ÛÙÔÈ¯Â›· ÁÈ· ÙËÓ ÔÚÂ›· ÙË˜ ÂÚ›ÙˆÛË˜. ¶·È‰È·ÙÚÈÎ‹ 2006;69:452-457

456

ª. ¶··Ê˘Ï·ÎÙÔ‡ Î·È Û˘Ó.

∂ÈÎﬁÓ· 4. ∏ ·/· ·ÚÈÛÙÂÚÔ‡ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡, ÌÂÙ¿ ·ﬁ 16 Ì‹ÓÂ˜ ıÂÚ·Â›·˜, ‰Â›¯ÓÂÈ Î‡ÚÙˆÛË ÙÔ˘ ÔÛÙÔ‡ Î·È ÏÂ˘Î¤˜ ˙ÒÓÂ˜ ÛÙËÓ Â›Ê˘ÛË.

™ÙËÓ ÂÚ›ÙˆÛË Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È, ·Ú·ÙËÚ‹ıËÎÂ ÌÂ›ˆÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ Î·È ·‡ÍËÛË ÙÔ˘ ‡„Ô˘˜ ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ ÌÂÙ¿ ·fi 12 Ì‹ÓÂ˜ ÂÓ‰ÔÊÏ¤‚È·˜ ıÂÚ·Â›·˜, Ô˘ Û˘ÌÊˆÓÔ‡Ó ÌÂ ÙË ‚È‚ÏÈÔÁÚ·Ê›· (2,3,5-7). √ÚÈÛÌ¤ÓÔÈ ÂÚÂ˘ÓËÙ¤˜ (5) ÚÔÙÂ›ÓÔ˘Ó ıÂÚ·Â›· ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ∞√ fiÙ·Ó ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ÂÚÈÛÛfiÙÂÚ· ·fi ‰‡Ô Î·Ù¿ÁÌ·Ù· ÂÙËÛ›ˆ˜ Î·È Î·ı›˙ËÛË ÙˆÓ ÛÔÓ‰‡ÏˆÓ. ™ÙËÓ ·ÚÔ‡Û· ÂÚ›ÙˆÛË, ÙÔ ‚Ú¤ÊÔ˜ ·ÚÔ˘Û›·ÛÂ ÙÚ›· Î·Ù¿ÁÌ·Ù· ÙÔ˘˜ ÚÒÙÔ˘˜ ÔÎÙÒ Ì‹ÓÂ˜ ÙË˜ ˙ˆ‹˜ ÙÔ˘ Î·È Î·ı›˙ËÛË ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ. ∞Ó·Ê¤ÚÂÙ·È (3,5) ÌÂ›ˆÛË ÙË˜ Û˘ÁÎ¤ÓÙÚˆÛË˜ ÙÔ˘ Ca++ ÛÙÔÓ ÔÚfi Î·È ·‡ÍËÛË ÙË˜ PTH ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ·ÓÂ¿ÚÎÂÈ· ‚ÈÙ·Ì›ÓË˜ D. ™ÙËÓ ÂÚ›ÙˆÛË Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È, ·Ú¿ ÙÈ˜ Ê˘ÛÈÔÏÔÁÈÎ¤˜ ÙÈÌ¤˜ ÙÔ˘ Ca++ Î·È ÙË˜ 25-√∏-D ÛÙÔ ·›Ì·, ·Ú·ÙËÚ‹ıËÎÂ ÛÙËÓ ÚÒÙË ¤Á¯˘ÛË ÙÒÛË ÙÔ˘ ÂÈ¤‰Ô˘ ÙÔ˘ Ca++ ÛÙÔÓ ÔÚfi, ·fi 10,5 mg/dl ÛÂ 8,2 mg/dl, Î·ıÒ˜ Î·È ÌÂÁ¿ÏË ·‡ÍËÛË ÙË˜ PTH, ·fi 20 pg/ml ÛÂ 105 pg/ml. ŒÙÛÈ, Û˘ÛÙ‹ıËÎÂ Û˘ÛÙËÌ·ÙÈÎ‹ ¯ÔÚ‹ÁËÛË ‚ÈÙ·Ì›ÓË˜ D (10 Ìg ËÌÂÚËÛ›ˆ˜) Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ıÂÚ·Â›·˜. ¶·ÚfiÌÔÈ· ‚ÈÔ¯ËÌÈÎ‹ ‰È·Ù·Ú·¯‹ ‰ÂÓ ÛËÌÂÈÒıËÎÂ ÛÙÈ˜ ÂfiÌÂÓÂ˜ ¤ÍÈ ÂÁ¯‡ÛÂÈ˜ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘. øÛÙfiÛÔ, ÛÙËÓ fiÁ‰ÔË Û˘ÓÂ‰Ú›· ·Ú·ÙËÚ‹ıËÎÂ ÌÈÎÚ‹ ·‡¶·È‰È·ÙÚÈÎ‹ 2006;69:452-457

ÍËÛË ÙÔ˘ ÂÈ¤‰Ô˘ ÙË˜ PTH ÛÙÔÓ ÔÚfi (80 pg/ml), ÂÓÒ Ë ÙÈÌ‹ ÙÔ˘ Ca++ ÛÙÔ ·›Ì· ‚Ú¤ıËÎÂ ÛÙ· ·ÓÒÙÂÚ· Ê˘ÛÈÔÏÔÁÈÎ¿ Â›Â‰· (11 mg/dl). ™ÙËÓ ÚÒÙË ¤Á¯˘ÛË ‰ÈÊˆÛÊÔÓÈÎÒÓ, ÂÚÈÁÚ¿ÊÂÙ·È Û‡Ó‰ÚÔÌÔ ÈÒÛÂˆ˜, ÌÂ ˘ÚÂÙfi, ÏÂ˘ÎÔÂÓ›· Î·È Ô˘‰ÂÙÂÚÔÂÓ›· (3,5). ™ÙÔ ‚Ú¤ÊÔ˜ ÙË˜ ·ÚÔ‡Û·˜ ÂÚ›ÙˆÛË˜ ·Ú·ÙËÚ‹ıËÎÂ, ÛÙËÓ ÚÒÙË Û˘ÓÂ‰Ú›·, ˘ÚÂÙfi˜ 39,5ÔC Î·È Ô˘‰ÂÙÂÚÔÂÓ›· (·fiÏ˘ÙÔ˜ ·ÚÈıÌfi˜ ¶: 132/mm3). ∆· ÎÏÈÓÈÎ¿ Û˘ÌÙÒÌ·Ù· ˘Ô¯ÒÚËÛ·Ó ÛÂ ‰‡Ô ËÌ¤ÚÂ˜ Î·È Ù· ·ÈÌ·ÙÔÏÔÁÈÎ¿ Â˘Ú‹Ì·Ù· ÛÂ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 10 ËÌÂÚÒÓ. √ ·ÛıÂÓ‹˜ ‰ÂÓ ÂÌÊ¿ÓÈÛÂ ·ÚfiÌÔÈ· ÎÏÈÓÈÎ¿ Î·È ·ÈÌ·ÙÔÏÔÁÈÎ¿ Â˘Ú‹Ì·Ù· ÛÙÈ˜ ÂfiÌÂÓÂ˜ ÂÁ¯‡ÛÂÈ˜. ™‡ÌÊˆÓ· ÌÂ Ù· ÎÏÈÓÈÎ¿, ‚ÈÔ¯ËÌÈÎ¿ Î·È ÌÔÚÈ·Î¿ Â˘Ú‹Ì·Ù·, Ô ·ÛıÂÓ‹˜ ·Ó‹ÎÂÈ ÛÙÔÓ Ù‡Ô IV ÙË˜ ∞√, Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ¯·ÌËÏfi ‡„Ô˜, ÛÎÔÏ›ˆÛË, ÏÂ˘ÎfiÊ·ÈÔ˘˜ ÛÎÏËÚÔ‡˜ Î·È ‰˘ÛÁÂÓÂÛ›· ÙˆÓ Ô‰fiÓÙˆÓ (5). √ÚÈÛÌ¤ÓÔÈ ŒÏÏËÓÂ˜ ÂÈÛÙ‹ÌÔÓÂ˜ (6) ·Ó·Ê¤ÚÔ˘Ó ·‡ÍËÛË ÙË˜ ∂£ ÙÔ˘ ‡„Ô˘˜ Î·È ‚ÂÏÙ›ˆÛË ÙÔ˘ ÛÎÂÏÂÙÔ‡ ·È‰ÈÒÓ ËÏÈÎ›·˜ 3-7 ÂÙÒÓ Ô˘ ·ÓÙÈÌÂÙˆ›ÛÙËÎ·Ó ÌÂ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ‰ÈÊˆÛÊÔÓÈÎ¿. ∆Ô ª™ ‚Ú¤ıËÎÂ, ÛÙËÓ ÂÚ›ÙˆÛË Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È, ÛÙË 10Ë ∂£ Ì¤¯ÚÈ ÙËÓ ËÏÈÎ›· ÙˆÓ 10 ÌËÓÒÓ Î·È ÌÂÙ¿ ÌÂÈÒıËÎÂ, Î¿Ùˆ ·fi ÙËÓ ÙÚ›ÙË ∂£, Ì¤¯ÚÈ ÙËÓ ËÏÈÎ›· ÙˆÓ 26 ÌËÓÒÓ. º·›ÓÂÙ·È fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÙË˜ ‰ÈÓ·ÙÚÈÔ‡¯Ô˘ ·ÌÈ‰ÚÔÓ¿ÙË˜ ‰ÂÓ ·Ó¤ÛÙÂÈÏÂ ÙË Ê˘ÛÈÎ‹ ÔÚÂ›· ÙË˜ ÓfiÛÔ˘ Û¯ÂÙÈÎ¿ ÌÂ ÙÔ ª™ ÙÔ˘ ·È‰ÈÔ‡, ·Ó Î·È Ô ·ÚÈıÌfi˜ ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ ÌÂÈÒıËÎÂ Î·È ÙÔ ‡„Ô˜ ÙˆÓ ÛÔÓ‰˘ÏÈÎÒÓ ÛˆÌ¿ÙˆÓ ·˘Í‹ıËÎÂ. ∏ ıÂÚ·Â›· ÙË˜ ÓfiÛÔ˘ Â›Ó·È Û˘ÌÙˆÌ·ÙÈÎ‹, ÌÂ ÌÂ›ˆÛË ÙË˜ ÔÛÙÂÔfiÚˆÛË˜ Î·È ÙË˜ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ, ·Ó·ÎÔ‡ÊÈÛË ·fi ÙÔ ¯ÚfiÓÈÔ ¿ÏÁÔ˜ Î·È ÙËÓ ÎfiˆÛË, ‚ÂÏÙ›ˆÛË ÙË˜ ÎÈÓËÙÈÎfiÙËÙ·˜ Î·È ÚfiÏË„Ë ÙˆÓ ·Ú·ÌÔÚÊÒÛÂˆÓ ÙˆÓ Ì·ÎÚÒÓ ÔÛÙÒÓ Î·È ÛÔÓ‰‡ÏˆÓ (2,3,5). ∞Ó·Ê¤ÚÂÙ·È ·‡ÍËÛË ÙÔ˘ µ™ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ıÂÚ·Â›·˜ (5). ™ÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ ‚Ú¤ÊÔ˘˜ ‰ÂÓ ·˘Í‹ıËÎÂ ˘ÂÚ‚ÔÏÈÎ¿ ÙÔ µ™. ™Â ËÏÈÎ›· 8 ÌËÓÒÓ ÙÔ µ™ ‚Ú¤ıËÎÂ 7560 g (3Ë-10Ë ∂£) Î·È ÛÂ ËÏÈÎ›· 26 ÌËÓÒÓ ÙÔ µ™ ‹Ù·Ó 10.500 g (<3Ë ∂£). √ÚıÔ·È‰ÈÎÔ› ·Ó·Ê¤ÚÔ˘Ó ÏÂ˘Î¤˜ ÂÚÈÔ¯¤˜ ÛÙÈ˜ ·ÎÙÈÓÔÁÚ·Ê›Â˜ ÙˆÓ ÂÈÊ‡ÛÂˆÓ ÙˆÓ Ì·ÎÚÒÓ ÔÛÙÒÓ ÌÂÙ¿ ·fi ıÂÚ·Â›· ÌÂ ‰ÈÊˆÛÊÔÓÈÎ¿ (7). ¶·ÚfiÌÔÈÂ˜ ÏÂ˘Îˆ¤˜ ˙ÒÓÂ˜ ·Ú·ÙËÚ‹ıËÎ·Ó Î·È ÛÙËÓ ·/· ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡ ÙÔ˘ ÓË›Ô˘ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È (∂ÈÎfiÓ· 4), fiˆ˜ Â›ÛË˜ ¤¯Ô˘Ó ·Ú·ÙËÚËıÂ› ÛÂ ·È‰È¿ ÌÂ Ú·¯›ÙÈ‰· ·ÓıÂÎÙÈÎ‹ ÛÙË ‚ÈÙ·Ì›ÓË D. ∞˘Ù‹ Ë ÂÈÎfiÓ· ıÂˆÚÂ›Ù·È fiÙÈ ‰ËÏÒÓÂÈ ‚ÂÏÙ›ˆÛË ÙË˜

457

∞ÙÂÏ‹˜ ÔÛÙÂÔÁ¤ÓÂÛË Î·È ·ÌÈ‰ÚÔÓ¿ÙË

·Û‚ÂÛÙÔÔ›ËÛË˜ ÙÔ˘ ÔÛÙÔ‡. ™˘ÛÙ‹ıËÎÂ Ë ÂÊ·ÚÌÔÁ‹ ÂÓ‰ÔÌ˘ÂÏÈÎÔ‡ ‹ÏÔ˘ ÛÙ· ÌËÚÈ·›· ÔÛÙ¿. ∂ÚÂ˘ÓËÙ¤˜ Û˘ÓÈÛÙÔ‡Ó ÙËÓ ÙÔÔı¤ÙËÛË ÂÓ‰ÔÌ˘ÂÏÈÎÔ‡ ‹ÏÔ˘ ÛÙÔ ÌËÚÈ·›Ô ÔÛÙfi Î·È ÙËÓ ÎÓ‹ÌË, ÁÈ· ÙË ‚ÂÏÙ›ˆÛË ÙË˜ ‚¿‰ÈÛË˜ Î·È ÙË˜ ÈÛÔÚÚÔ›·˜ (5,6). ∏ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ¯ÔÚ‹ÁËÛË ‰ÈÊˆÛÊÔÓÈÎÒÓ ÛÂ ·È‰È¿ ËÏÈÎ›·˜ 6-15 ÂÙÒÓ ·Ó·Ê¤ÚÂÙ·È ·fi ÔÚıÔ·È‰ÈÎÔ‡˜ ·fi ÙËÓ ∫ÔÚ¤·, ÌÂ ÈÎ·ÓÔÔÈËÙÈÎ¿ ·ÔÙÂÏ¤ÛÌ·Ù· ˆ˜ ÚÔ˜ ÙËÓ ÔÛÙÂÔfiÚˆÛË Î·È Ù· Î·Ù¿ÁÌ·Ù· (7). ™ÙËÓ ∂ÏÏ¿‰·, ¯ÔÚËÁ‹ıËÎ·Ó ‰ÈÊˆÛÊÔÓÈÎ¿ 30 mg Â‚‰ÔÌ·‰È·›ˆ˜ ÛÂ ‰‡Ô ÎÔÚ›ÙÛÈ· ÌÂ ∞√ ÁÈ· 15 Ì‹ÓÂ˜ Î·È ·Ú·ÙËÚ‹ıËÎÂ ·‡ÍËÛË ÙË˜ ÔÛÙÈÎ‹˜ Ì¿˙·˜, ¯ˆÚ›˜ Ó¤Ô Î¿Ù·ÁÌ· ÛÂ ‰È¿ÛÙËÌ· 4 ÂÙÒÓ. ™‡ÌÊˆÓ· ÌÂ ÂÚÂ˘ÓËÙ¤˜ (3,5,8), ˘¿Ú¯Ô˘Ó Î¿ÔÈ· ·Ó·¿ÓÙËÙ· ÂÚˆÙ‹Ì·Ù· Û¯ÂÙÈÎ¿ ÌÂ ÙË ¯Ú‹ÛË ÙˆÓ ‰ÈÊˆÛÊÔÓÈÎÒÓ, Ù· ÔÔ›· Î˘Ú›ˆ˜ ·ÊÔÚÔ‡Ó ÛÙ· ·ÎfiÏÔ˘ı·: ·) ∫·ıËÏÒÓÔÓÙ·È ÛÙ· ÔÛÙ¿ ÁÈ· ‰ÂÎ·ÂÙ›Â˜ Î·È ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹ Ë Â›ÙˆÛ‹ ÙÔ˘˜ ·fi ÙÔÓ ÌËÙÚÈÎfi ÛÎÂÏÂÙfi ÛÙÔ ¤Ì‚Ú˘Ô. ‚) ∏ ¯Ú‹ÛË ÙÔ˘˜ ÌÔÚÂ› Ó· Â›Ó·È ‰˘ÛÌÂÓ‹˜ ÛÙÔ˘˜ ÂÊ‹‚Ô˘˜, ‰ÈfiÙÈ ÚÔÎ·ÏÔ‡Ó ÌÂ›ˆÛË ÙÔ˘ ·Ó·Û¯ËÌ·ÙÈÛÌÔ‡ ÙÔ˘ ÔÛÙÔ‡ (remodeling). Á) ¢ÂÓ Â›Ó·È ÁÓˆÛÙfi˜ Ô ¯ÚfiÓÔ˜ Ô˘ ı· ‰È·ÚÎ¤ÛÂÈ Ë ‚ÂÏÙ›ˆÛË, ·ÏÏ¿ Î·È ÔÈ ÂÈÙÒÛÂÈ˜. ‰) ™Ù· ·È‰È¿ ÌÂ ÙËÓ ‹È· ÌÔÚÊ‹ ÙË˜ ÓfiÛÔ˘ ‰ÂÓ Û˘ÓÈÛÙ¿Ù·È ıÂÚ·Â›·. ¶ÚÔ˜ ÙÔ ·ÚfiÓ, Ë ·ÔÙÂÏÂÛÌ·ÙÈÎ‹ Û˘ÌÙˆÌ·ÙÈÎ‹ ·ÓÙÈÌÂÙÒÈÛË ÛÙÈ˜ Ì¤ÙÚÈÂ˜ Î·È ÛÔ‚·Ú¤˜ ÌÔÚÊ¤˜ ÙË˜ ∞√ Â›Ó·È Ë ¯ÔÚ‹ÁËÛË ÙˆÓ ‰ÈÊˆÛÊÔÓÈÎÒÓ. ªÂ Ù· ‰ÈÊˆÛÊÔÓÈÎ¿ ‰ÂÓ ·Ú·ÙËÚ‹ıËÎÂ Â˘ÓÔ˚Î‹ Â›‰Ú·ÛË ÛÙÔ ª™ Î·È, ÂÔÌ¤Óˆ˜, ÛÙÔ ÁÂÓÂÙÈÎfi ˘fiÛÙÚˆÌ· ÙË˜ ÓfiÛÔ˘, ÂÓÒ ·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙË Ë Ì·ÎÚÔ¯ÚfiÓÈ· ¤Î‚·ÛË ÙË˜ ¯ÔÚ‹ÁËÛ‹˜ ÙÔ˘˜.

∂˘¯·ÚÈÛÙ›Â˜ ∂˘¯·ÚÈÛÙÔ‡ÌÂ ıÂÚÌ¿ ÙÔÓ ∫·ıËÁËÙ‹ Î. N. Bishop ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ Sheffield ÙÔ˘ ∏ÓˆÌ¤ÓÔ˘ µ·ÛÈÏÂ›Ô˘, Ô˘ ÚÔ¤ÙÚÂ„Â ÙÔ˘˜ ÁÔÓÂ›˜ ÙÔ˘ ÓË›Ô˘ Ó· ·ÓÙÈÌÂÙˆ›ÛÔ˘Ó ÙË ÓﬁÛÔ ÙÔ˘ ·È‰ÈÔ‡ ÙÔ˘˜ ÛÙËÓ ∂ÏÏ¿‰·.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Glorieux FH. A disease of the osteoblast. Lancet 2001;358 (Suppl): S45. 2. Landsmeer-Beker EA, Massa GG, Maaswinkel-Mooy PD, van de Kamp JJ, Papapoulos SE. Treatment of osteogenesis imperfecta with the bisphosphonate olpadronate (dimethylaminohydroxypropylidene bisphosphonate). Eur J Pediatr 1997;156:792-794. 3. Plotkin H, Rauch F, Bishop NJ, Montpetit K, RuckGibis J, Travers R et al. Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 2000;85:1846-1850. 4. ∫ÒÛÙ·ÏÔ˜ Ã, √ÈÎÔÓÔÌ›‰Ô˘ √. ÃÔÚ‹ÁËÛË ‰ÈÓ·ÙÚÈÔ‡¯Ô˘ ·ÌÈ‰ÚÔÓ¿ÙË˜ ÛÂ ÓÂÔÁÓfi. 38Ô ¶·ÓÂÏÏ‹ÓÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ; ∫ˆ˜: 16-18 πÔ˘Ó›Ô˘ 2000. 5. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet 2004;363:1377-1385. 6. µÔÛÎ¿ÎË ∂, ∞ı·Ó·ÛÔÔ‡ÏÔ˘ ∂, °ÂˆÚÁ·ÎÔÔ‡ÏÔ˘ ∞. £ÂÚ·Â˘ÙÈÎ¿ ·ÔÙÂÏ¤ÛÌ·Ù· ÙË˜ ·ÏÏÂÓ‰ÚÔÓ¿ÙË˜ ÛÂ ·È‰È¿ ÌÂ ·ÙÂÏ‹ ÔÛÙÂÔÁ¤ÓÂÛË. 43Ô ¶·ÓÂÏÏ‹ÓÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ; ∫ˆ˜: 17-19 πÔ˘Ó›Ô˘ 2005. 7. Cho TJ, Choi IH, Chung CY, Yoo WJ, Park MS, Park YK. Efficacy of oral alendronate in children with osteogenesis imperfecta. J Pediatr Orthop 2005;25: 607612. 8. Marini JC. Do bisphosphonates make children’s bones better or brittle? N Engl J Med 2003;349:423-426.

¶·È‰È·ÙÚÈÎ‹ 2006;69:452-457

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¶·Ú·ÛÔÓ‰˘ÏÈÎfi ÂÍˆÔÛÙÈÎfi Û¿ÚÎˆÌ· ÙÔ˘ Ewing: ÂÚÈÁÚ·Ê‹ ‰‡Ô ÂÚÈÙÒÛÂˆÓ 1 µ’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ∞.¶.£, ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∞Ã∂¶∞ 2 ¶·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎfi ∂ÚÁ·ÛÙ‹ÚÈÔ ∞.¶.£., ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∞Ã∂¶∞ 3 ¡Â˘ÚÔ¯ÂÈÚÔ˘ÚÁÈÎ‹ ∫ÏÈÓÈÎ‹ ∞.¶.£., ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∞Ã∂¶∞ 4 ∞ÎÙÈÓÔÏÔÁÈÎfi ∂ÚÁ·ÛÙ‹ÚÈÔ ∞.¶.£., ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∞Ã∂¶∞ AÏÏËÏÔÁÚ·Ê›·: º·Ó‹ ∞ı·Ó·ÛÈ¿‰Ô˘¶ÈÂÚÔÔ‡ÏÔ˘, ªËÙÚÔfiÏÂˆ˜ 55, ∆.∫. 54623, £ÂÛÛ·ÏÔÓ›ÎË E-mail: fathanassiadou@hotmail.com atriagia@auth.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 31-05-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 05-09-2006

º. ∞ı·Ó·ÛÈ¿‰Ô˘1, ∞. ∆Ú·ÁÈ·ÓÓ›‰Ë˜1, ª. ∫Ô‡ÚÙË1, £. ¶··ÁÂˆÚÁ›Ô˘1, ¶. Ã˘Ù›ÚÔÁÏÔ˘2, µ. ∫ÔÓÙﬁÔ˘ÏÔ˜3, ∞. ∫·ÏÔÁÂÚ¿4, ∞. ¢ÚÂ‚ÂÏ¤ÁÎ·˜4

¶ÂÚ›ÏË„Ë: ∆Ô ÂÍˆÔÛÙÈÎfi Û¿ÚÎˆÌ· ÙÔ˘ Ewing (Extraskeletal Ewing’s Sarcoma, EES) Â›Ó·È Û¿ÓÈÔ, ˘„ËÏ‹˜ Î·ÎÔ‹ıÂÈ·˜ ÓÂfiÏ·ÛÌ· ÙˆÓ ÔÛÙÒÓ ÌÂ ÈÛÙÔÏÔÁÈÎÔ‡˜ ¯·Ú·ÎÙ‹ÚÂ˜ ·Ó¿ÏÔÁÔ˘˜ ÌÂ ÂÎÂ›ÓÔ˘˜ ÙÔ˘ Û·ÚÎÒÌ·ÙÔ˜ ÙÔ˘ Ewing (Ewing’s Sarcoma, EWS). ∆Ô EES ··ÓÙ¿Ù·È Î˘Ú›ˆ˜ ÛÂ ÂÊ‹‚Ô˘˜ Î·È ÓÂ·ÚÔ‡˜ ÂÓ‹ÏÈÎÂ˜ Î·È ÂÍÔÚÌ¿Ù·È Û˘¯ÓfiÙÂÚ· ·fi ÙËÓ ·Ú·ÛÔÓ‰˘ÏÈÎ‹ ÂÚÈÔ¯‹ Î·È Ù· Î¿Ùˆ ¿ÎÚ·. ¶ÂÚÈÁÚ¿ÊÔÓÙ·È 2 ÂÚÈÙÒÛÂÈ˜ EES ÌÂ ÂÓÙfiÈÛË ÙÔ˘ fiÁÎÔ˘ ·Ú·ÛÔÓ‰˘ÏÈÎ¿, ÛÂ ·È‰È¿ ËÏÈÎ›·˜ 14 Î·È 10 ÂÙÒÓ, ·ÓÙ›ÛÙÔÈ¯·. √È 2 ·ÛıÂÓÂ›˜ ·Ó¤ÊÂÚ·Ó Ú·¯È·ÏÁ›· Î·È ÏÂ˘ÚÔ‰˘Ó›· Î·È Ë ‰È¿ÁÓˆÛË ‚·Û›ÛÙËÎÂ ÛÙ· Â˘Ú‹Ì·Ù· ÙÔ˘ ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂÏ¤Á¯Ô˘ Î·È ÙË˜ ÈÛÙÔÏÔÁÈÎ‹˜/·ÓÔÛÔ˚ÛÙÔ¯ËÌÈÎ‹˜ ·Ó¿Ï˘ÛË˜ Ô˘ ·ÔÎ¿Ï˘„Â ÙËÓ ‡·ÚÍË Î·ÎÔ‹ıÔ˘˜ ÓÂÔÏ¿ÛÌ·ÙÔ˜ ·fi ÌÈÎÚ¿ ÛÙÚÔÁÁ˘Ï¿, ÌÏÂ Î‡ÙÙ·Ú·, ÌÂ ¯·Ú·ÎÙ‹ÚÂ˜ Û˘Ì‚·ÙÔ‡˜ ÌÂ Û¿ÚÎˆÌ· Ewing/PNET. ∏ ÌÔÚÈ·Î‹ ‰ÈÂÚÂ‡ÓËÛË Ô˘ ·ÎÔÏÔ‡ıËÛÂ ÌÂ RT-PCR ·ÔÎ¿Ï˘„Â ÙËÓ ·ÚÔ˘Û›· ˘‚ÚÈ‰ÈÎÒÓ ÌÂÙ·ÁÚ·ÊËÌ¿ÙˆÓ EWS-FLI-1 [t(11;22) (q24;q12)]. ∏ ÌÂÙ¿ıÂÛË ·˘Ù‹ ÙÂÎÌËÚ›ˆÛÂ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ EES Î·È ÛÙÔ˘˜ 2 ·ÛıÂÓÂ›˜, ÔÈ ÔÔ›ÔÈ ˘Ô‚Ï‹ıËÎ·Ó ÛÂ ¯ÂÈÚÔ˘ÚÁÈÎ‹ ·Ê·›ÚÂÛË ÙÔ˘ fiÁÎÔ˘ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ÛÂ ıÂÚ·Â›· (¯ËÌÂÈÔ-, ·ÎÙÈÓÔıÂÚ·Â›·) ÌÂ ÂÈ‰ÈÎfi ÚˆÙfiÎÔÏÏÔ ÁÈ· Û¿ÚÎˆÌ· ÙÔ˘ Ewing (IESS NCI) Û˘ÓÔÏÈÎ‹˜ ‰È¿ÚÎÂÈ·˜ 51 Â‚‰ÔÌ¿‰ˆÓ ¯ˆÚ›˜ ˘ÔÙÚÔ‹ ÙË˜ ÓfiÛÔ˘ ‹ ¿ÏÏÂ˜ ÂÈÏÔÎ¤˜. §¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ∂ÍˆÔÛÙÈÎfi Û¿ÚÎˆÌ· ÙÔ˘ Ewing, ·Ú·ÛÔÓ‰˘ÏÈÎ‹ ÂÚÈÔ¯‹, Ú·¯È·ÏÁ›·.

Extraskeletal Ewing’s sarcoma: report of 2 cases 1 2nd Paediatric Clinic, Aristotle University of Thessaloniki, University Hospital AHEPA 2 Pathology Laboratory, Aristotle University of Thessaloniki, University Hospital AHEPA 3 Neurosurgery Clinic, Aristotle University of Thessaloniki, University Hospital AHEPA 4 Radiology Laboratory, Aristotle University of Thessaloniki, University Hospital AHEPA Correspondence: Fani AthanassiadouPiperopoulou 55, Mitropoleos St. 54623, Thessaloniki E-mail: fathanassiadou@hotmail.com atriagia@auth.gr Date of submission: 31-05-2005 Date of approval: 05-09-2006

¶·È‰È·ÙÚÈÎ‹ 2006;69:458-462

F. Athanassiadou1, A. Tragiannidis1, M. Kourti1, T. Papageorgiou1, P. Chytiroglou2, V. Kontopoulos3, A. Kalogera4, A. Drevelegas4

Abstract: Extraskeletal Ewing’s sarcoma (EES) is a rare soft tissue malignant neoplasm histologically similar to skeletal Ewing’s sarcoma (EWS). EES occurs mainly in adolescents and young adults and commonly affects the paravertebral regions and the lower limbs. Two cases of EES in 14 and 10 year-old children are reported, involving the paravertebral spaces. The diagnosis of EES was based on the clinical symptoms (back and chest pain) and radiological findings and on the histologic/immunohistochemistry features of a malignant tumour with small, blue, round cells indicative of Ewing’s/PNET. The diagnosis of EES was confirmed by RT-PCR, which showed the presence of the EWS/FLI-1 fusion transcript [t(11;22) (q24;q12) chromosomal translocation]. Both patients were treated by surgical resection of the mass and subsequent chemo- and radiotherapy (IESS NCI protocol) for a total of 51 weeks, without relapse or other complications. Key words: Extraskeletal Ewing’s sarcoma, paravertebral region, back pain.

∂ÈÛ·ÁˆÁ‹ ∆Ô Û¿ÚÎˆÌ· ÙÔ˘ ∂wing (EWS) Â›Ó·È Û¿ÓÈÔ, ˘„ËÏ‹˜ Î·ÎÔ‹ıÂÈ·˜ ÓÂfiÏ·ÛÌ· ÙˆÓ ÔÛÙÒÓ. ¶·ÚfiÙÈ ÙÔ EWS Â›Ó·È ¤Ó·˜ ·‰È·ÊÔÚÔÔ›ËÙÔ˜ fiÁÎÔ˜ ÙˆÓ ÔÛÙÒÓ, Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÂÍÔÚÌ¿Ù·È ·fi Ù· Ì·Ï·Î¿ ÌfiÚÈ· (ÂÍˆÔÛÙÈÎfi Û¿ÚÎˆÌ· ÙÔ˘ Ewing) (1-3). ∂ÈÏ¤ÔÓ, ÌÈ· Ï¤ÔÓ ‰È·ÊÔÚÔÔÈËÌ¤ÓË ÌÔÚÊ‹ ÙÔ˘ fiÁÎÔ˘, ·ÔÙÂÏÂ› ÙÔ ÓÂ˘-

ÚÔÂÈıËÏ›ˆÌ· ‹ ÂÚÈÊÂÚÈÎfi˜ ÚˆÙÔ·ı‹˜ ÓÂ˘ÚÔ-ÂÈıËÏÈ·Îfi˜ fiÁÎÔ˜ (ƒ¡∂∆), Ô˘ ÌÔÚÂ› Ó· ÂÍÔÚÌ¿Ù·È Â›ÙÂ ·fi Ù· ÔÛÙ¿ Â›ÙÂ ·fi Ù· Ì·Ï·Î¿ ÌfiÚÈ·. ŸÏÂ˜ ·˘Ù¤˜ ÔÈ ÌÔÚÊ¤˜ ÂÌÊ·Ó›˙Ô˘Ó ·ÚfiÌÔÈ· ÈÛÙÔ¯ËÌÈÎ¿ Î·È ‚ÈÔÏÔÁÈÎ¿ ¯·Ú·ÎÙËÚÈÛÙÈÎ¿ Î·È ÂÔÌ¤Óˆ˜ Î·Ù·Ù¿ÛÛÔÓÙ·È ÛÂ ÌÈ· ÂÓÈ·›· ÔÌ¿‰· fiÁÎˆÓ, ÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ Û·ÚÎˆÌ¿ÙˆÓ ÙÔ˘ Ewing (Ewing’s Sarcoma family tumors, ESFT). ™¯ÂÙÈÎ¿ ÌÂ ÙËÓ ÚÔ¤ÏÂ˘ÛË ÙÔ˘

459

¶·Ú·ÛÔÓ‰˘ÏÈÎﬁ ÂÍˆÔÛÙÈÎﬁ Û¿ÚÎˆÌ· ÙÔ˘ Ewing

fiÁÎÔ˘ ÂÈÎÚ·ÙÂ› Ë ¿Ô„Ë fiÙÈ ÙÔ ‚·ÛÈÎfi Î‡ÙÙ·ÚÔ Â›Ó·È ¤Ó· ·Ú¯¤ÁÔÓÔ ÔÏ˘‰‡Ó·ÌÔ ÓÂ˘ÚÈÎfi Î‡ÙÙ·ÚÔ, Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi ÙÔ ·Ú·Û˘Ì·ıËÙÈÎfi ÓÂ˘ÚÈÎfi Û‡ÛÙËÌ·, ÂÚÌËÓÂ‡ÔÓÙ·˜ ¤ÙÛÈ ÙËÓ ÔÈÎÈÏ›· ÂÓÙfiÈÛË˜ ÙˆÓ fiÁÎˆÓ ÙË˜ Î·ÙËÁÔÚ›·˜ ·˘Ù‹˜. ™˘¯ÓfiÙÂÚÂ˜ ı¤ÛÂÈ˜ ÂÓÙfiÈÛË˜ ÙÔ˘ EES Â›Ó·È Ô ıÒÚ·Î·˜, Ù· Î¿Ùˆ ¿ÎÚ· Î·È Ë ·Ú·ÛÔÓ‰˘ÏÈÎ‹ ÂÚÈÔ¯‹ Î·È ··ÓÙ¿Ù·È Û˘¯ÓfiÙÂÚ· ÛÂ ÓÂ·ÚÔ‡˜ ÂÓ‹ÏÈÎÂ˜ (<30 ÂÙÒÓ) (1,4).

¶ÂÚ›ÙˆÛË ÚÒÙË ∞ÁfiÚÈ ËÏÈÎ›·˜ 14 ÂÙÒÓ ‰È·ÎÔÌ›ÛÙËÎÂ ÛÙËÓ ÎÏÈÓÈÎ‹ Ì·˜ ·fi √ÚıÔ·È‰ÈÎ‹ ∫ÏÈÓÈÎ‹ ·ÎÈÓËÙÔÔÈËÌ¤ÓÔ ÛÂ Á‡„ÈÓÔ Ó¿ÚıËÎ·, ÏfiÁˆ ÔÛÙÂÔÏ˘ÙÈÎ‹˜ ÂÍÂÚÁ·Û›·˜ ÙÔ˘ £-9 ÛÔÓ‰‡ÏÔ˘ Ô˘ ·ÔÎ·Ï‡ÊıËÎÂ ÌÂ ·Ï‹ ·ÎÙÈÓÔÁÚ·Ê›· (∂ÈÎfiÓ· 1). ∞fi ÙÔ ÈÛÙÔÚÈÎfi ·Ó·Ê¤ÚÂÙ·È Ú·¯È·ÏÁ›· ·fi ‰ÈÌ‹ÓÔ˘ ÌÂ Â›Ù·ÛË ÙÔ˘ ¿ÏÁÔ˘˜ Î·Ù¿ ÙËÓ Î¿Ì„Ë¤ÎÙ·ÛË ÙÔ˘ ÎÔÚÌÔ‡. ∏ ÓÂ˘ÚÔÏÔÁÈÎ‹ ÂÎÙ›ÌËÛË Î·È Ë ·ÓÙÈÎÂÈÌÂÓÈÎ‹ ÂÍ¤Ù·ÛË Î·Ù¿ Û˘ÛÙ‹Ì·Ù· ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎ‹. √ Ú·‰ÈÔ˚ÛÔÙÔÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÌÂ ÛÈÓıËÚÔÁÚ¿ÊËÌ· ÙˆÓ ÔÛÙÒÓ ·ÔÎ¿Ï˘„Â ÙËÓ ‡·ÚÍË ÂÚÈÔ¯‹˜ ·˘ÍËÌ¤ÓË˜ ÛÈÓıËÚÔÁÚ·ÊÈÎ‹˜ ·ÓÙ›ıÂÛË˜ ÛÙÔ ‡„Ô˜ ÙÔ˘ £-9, Â‡ÚËÌ· Ô˘ ·Ô‰fiıËÎÂ ÛÂ Î¿Ù·ÁÌ· ÙÔ˘ ÛÔÓ‰‡ÏÔ˘, ÂÓÒ ÛÙ· ˘fiÏÔÈ· ÔÛÙ¿ Ë Î·ı‹ÏˆÛË ÙÔ˘ Ú·‰ÈÔÊ·ÚÌ¿ÎÔ˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎ‹. √ ¤ÏÂÁ¯Ô˜ ÔÏÔÎÏËÚÒıËÎÂ ÌÂ CT Î·È MRI ÙË˜ ıˆÚ·ÎÈÎ‹˜ ÌÔ›Ú·˜ ÙË˜ ÛÔÓ‰˘ÏÈÎ‹˜ ÛÙ‹ÏË˜ Ô˘ ·ÔÎ¿Ï˘„·Ó ÂÈÎfiÓ· ·Ô‰ÈÔÚÁ¿ÓˆÛË˜ ÌÂ ‰È¿Û·ÛË ÙÔ˘ ÊÏÔÈÔ‡ Î·È Î·ı›˙ËÛË ÙÔ˘ ÛÒÌ·ÙÔ˜ ÙÔ˘ £-9 Î·È ÙËÓ ‡·ÚÍË ·Ú·ÛÔÓ‰˘ÏÈÎ‹˜ ÂÍˆÔÛÙÈÎ‹˜ ¯ˆÚÔÎ·Ù·ÎÙËÙÈÎ‹˜ ÂÍÂÚÁ·Û›·˜ ‰ÂÍÈ¿, ÌÂ Â¤ÎÙ·ÛË ÛÙÔÓ Û‡ÛÙÔÈ¯Ô ÂÈÛÎÏËÚ›‰ÈÔ ¯ÒÚÔ Ô˘ È¤˙ÂÈ, ·ÏÏ¿ ‰ÂÓ ‰ÈËıÂ› ÙÔ ÛÒÌ· ÙÔ˘ ÛÔÓ‰‡ÏÔ˘ (∂ÈÎfiÓ· 2). √ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËÎÂ ÛÂ Î·ÙÂ˘ı˘ÓfiÌÂÓË ‚ÈÔ„›· ÌÂ ‚ÂÏfiÓË ·fi ÙËÓ ·Ú·ÛÔÓ‰˘ÏÈÎ‹ Ì¿˙· Ô˘ ·ÔÎ¿Ï˘„Â ÙËÓ ‡·ÚÍË Î·ÎÔ‹ıÔ˘˜ ÓÂÔÏ¿ÛÌ·ÙÔ˜ ·fi ÌÈÎÚ¿ ÛÙÚÔÁÁ˘Ï¿, ÌÏÂ

∂ÈÎﬁÓ· 1. ∞ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·ÎÔ˜. √ÛÙÂÔÏ˘ÙÈÎ‹ ÂÍÂÚÁ·Û›· ÛÔÓ‰‡ÏÔ˘ £-9.

Î‡ÙÙ·Ú·, ¯·Ú·ÎÙ‹ÚÂ˜ Û˘Ì‚·ÙÔ› ÌÂ Û¿ÚÎˆÌ· Ewing/PNET. ∞ÎÔÏÔ‡ıËÛÂ Û˘ÌÏËÚˆÌ·ÙÈÎfi fiÚÈÛÌ· ÌÔÚÈ·Î‹˜ ‰ÈÂÚÂ‡ÓËÛË˜ fiÔ˘ ÌÂ RTPCR ¤ÁÈÓÂ ¤ÏÂÁ¯Ô˜ ÁÈ· ÙËÓ ‡·ÚÍË ˘‚ÚÈ‰ÈÎÒÓ ÌÂÙ·ÁÚ·ÊÒÓ EWS-FLI-1 [t(11;22) (q24;q12)]. ∆Ô ˘ÏÈÎfi ‹Ù·Ó ıÂÙÈÎfi ÁÈ· ÙË ÌÂÙ¿ıÂÛË ÙÂÎÌËÚÈÒÓÔÓÙ·˜ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ ÂÍˆÔÛÙÈÎÔ‡ Û·ÚÎÒÌ·ÙÔ˜ ÙÔ˘ Ewing. ∂ÈÏ¤ÔÓ, Ô ÚÔ‚ÏÂfiÌÂÓÔ˜ ‰È·ÁÓˆÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ Ô˘ ‰ÈÂÓÂÚÁ‹ıËÎÂ ÁÈ· ÙËÓ ‡·ÚÍË ÌÂÙ·ÛÙ¿ÛÂˆÓ ·¤‚Ë ·ÚÓËÙÈÎfi˜. √ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËÎÂ ÛÂ ¯ËÌÂÈÔıÂÚ·Â›· ÌÂ ÂÈ‰ÈÎfi ÚˆÙfiÎÔÏÏÔ ÁÈ· Û¿ÚÎˆÌ· ÙÔ˘ Ewing (IESS NCI; Intergroup Ewing’s Sarcoma Study, National Cancer Institute protocol) Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÈÊˆÛÊ·Ì›‰Ë, ÂÙÔÔÛ›‰Ë, ‚ÈÓÎÚÈÛÙ›ÓË, ‰ÔÍÔÚÔ˘‚ÈÎ›ÓË, Î˘ÎÏÔÊˆÛÊ·Ì›‰Ë Î·È ·‰ÚÈ·Ì˘Î›ÓË (5). ¢‡Ô Ì‹ÓÂ˜ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË ÙË˜ ¯ËÌÂÈÔıÂÚ·Â›·˜ Ô ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËÎÂ ÛÂ ÛˆÌ·ÙÂÎÙÔÌ‹ £-9, ·Ê·›ÚÂÛË ÙË˜ ˘ÔÏÂÈÌÌ·ÙÈÎ‹˜ ÂÍÂÚÁ·Û›·˜ Î·È ÛÔÓ‰˘ÏÔ‰ÂÛ›· £8-£10 ÌÂ ÙÔÔı¤ÙËÛË ÎÏˆ‚Ô‡ ÙÈÙ·Ó›Ô˘ Î·È ‚È‰ÒÓ ÛÙ· ÛÒÌ·Ù· £8-£10 ÌÂ ·ÚÂÌ‚ÔÏ‹ Ú¿‚‰Ô˘ ÌÂ ‰ÂÍÈ¿ ıˆÚ·ÎÔÙÔÌ‹ (∂ÈÎfiÓ· 3). ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈÎ‹ ÙÔ˘ ÔÚÂ›· ‹Ù·Ó ÔÌ·Ï‹. √ ·ÛıÂÓ‹˜ Û˘Ó¤¯ÈÛÂ ÙÔ ¯ËÌÂÈÔıÂÚ·Â˘ÙÈÎfi ÚˆÙfiÎÔÏÏÔ Î·È ‰‡Ô Ì‹ÓÂ˜ ·ÚÁfiÙÂÚ· ˘Ô‚Ï‹ıËÎÂ ÛÂ ·ÎÙÈÓÔıÂÚ·Â›· ÁÈ· ‰È¿ÛÙËÌ· ÂÓfi˜ Ì‹Ó· ÂÚ›Ô˘, fiÔ˘ ¤Ï·‚Â ÛÙËÓ ÂÚÈÔ¯‹ £8-£10 ‰fiÛË 42Gy ÛÂ 23 Û˘ÓÂ‰Ú›Â˜. ŒÎÙÔÙÂ, Ô ·ÛıÂÓ‹˜ ‚Ú›ÛÎÂÙ·È ÛÂ ¿ÚÈÛÙË ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË Î·È ÔÏÔÎÏ‹ÚˆÛÂ ÙÔ ¯ËÌÂÈÔıÂÚ·Â˘ÙÈÎfi Û¯‹Ì· Û˘ÓÔÏÈÎ‹˜ ‰È¿ÚÎÂÈ·˜ 51 Â‚‰ÔÌ¿‰ˆÓ ¯ˆÚ›˜ ˘ÔÙÚÔ‹ ÙË˜ ÓfiÛÔ˘ ‹ ¿ÏÏÂ˜ ÂÈÏÔÎ¤˜.

¶ÂÚ›ÙˆÛË ‰Â‡ÙÂÚË ∫ÔÚ›ÙÛÈ ËÏÈÎ›·˜ 10 ÂÙÒÓ ÂÈÛ‹¯ıË ÛÙËÓ ÎÏÈÓÈÎ‹ Ì·˜ ÏﬁÁˆ ÏÂ˘ÚÔ‰˘Ó›·˜ Î·È ÔÛÊ˘·ÏÁ›·˜ ·ﬁ 20ËÌ¤ÚÔ˘ Î˘Ú›ˆ˜ Î·Ù¿ ÙË Ó˘¯ÙÂÚÈÓ‹ Î·Ù¿ÎÏÈÛË.

∂ÈÎﬁÓ· 2. ª·ÁÓËÙÈÎ‹ ÙÔÌÔÁÚ·Ê›· ıˆÚ·ÎÈÎ‹˜ ÌÔ›Ú·˜ ÛÔÓ‰˘ÏÈÎ‹˜ ÛÙ‹ÏË˜. ⁄·ÚÍË ·Ú·ÛÔÓ‰˘ÏÈÎ‹˜ ÂÍˆÛÎÏËÚ›‰È·˜ ¯ˆÚÔÎ·Ù·ÎÙËÙÈÎ‹˜ ÂÍÂÚÁ·Û›·˜ ÌÂ Â¤ÎÙ·ÛË ÛÙÔÓ ÂÈÛÎÏËÚ›‰ÈÔ ¯ÒÚÔ Î·È ›ÂÛË ÛÙÔ ÓˆÙÈ·›Ô Ì˘ÂÏﬁ. ¶·È‰È·ÙÚÈÎ‹ 2006;69:458-462

460

º. ∞ı·Ó·ÛÈ¿‰Ô˘ Î·È Û˘Ó.

∂ÈÎﬁÓ· 3. ∞ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·ÎÔ˜ ÌÂÙÂÁ¯ÂÈÚËÙÈÎ¿. ∞ÂÈÎﬁÓÈÛË ÎÏˆ‚Ô‡ ÙÈÙ·Ó›Ô˘ ÛÙ· ÛÒÌ·Ù· £8-£10 ÌÂ ·ÚÂÌ‚ÔÏ‹ Ú¿‚‰Ô˘.

∏ ·ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·ÎÔ˜ ·ÔÎ¿Ï˘„Â ÙËÓ ·ÚÔ˘Û›· ·ÎÙÈÓÔÛÎÈÂÚ‹˜ ÂÚÈÔ¯‹˜ ÛÙÔ Ì¤ÛÔ Î·È Î¿Ùˆ ÓÂ˘ÌÔÓÈÎfi Â‰›Ô ‰ÂÍÈ¿, ÌÂ Û˘ÓÔ‰fi ‰È¿‚ÚˆÛË ÙË˜ 7Ë˜ ÏÂ˘Ú¿˜ Î·È ‰È¿‚ÚˆÛË-ÛÊËÓÔÂÈ‰‹ ·Ú·ÌfiÚÊˆÛË ÙÔ˘ ÛÒÌ·ÙÔ˜ ÙÔ˘ £-7 ÛÔÓ‰‡ÏÔ˘. ¢ÈÂÓÂÚÁ‹ıËÎÂ Ï‹ÚË˜ ·ÈÌ·ÙÔÏÔÁÈÎfi˜‚ÈÔ¯ËÌÈÎfi˜ ¤ÏÂÁ¯Ô˜ Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜, ÂÓÒ ÔÏÔÎÏËÚÒıËÎÂ Ô ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÌÂ ÛÈÓıËÚÔÁÚ¿ÊËÌ· ÔÛÙÒÓ, fiÔ˘ Î·Ù·ÁÚ¿ÊËÎÂ ·˘ÍËÌ¤ÓË ÌÂÙ·‚ÔÏÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ· ÛÙÔ ÛÒÌ· ÙÔ˘ £-7 ÛÔÓ‰‡ÏÔ˘ Î·È ÛÙÔ ÙfiÍÔ ÙË˜ 7Ë˜ ÏÂ˘Ú¿˜ ‰ÂÍÈ¿. √ ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÌÂ CT ıÒÚ·ÎÔ˜-ÎÔÈÏ›·˜ Î·È MRI ıÒÚ·ÎÔ˜ ·ÔÎ¿Ï˘„Â ÙËÓ ·ÚÔ˘Û›· Â˘ÌÂÁ¤ıÔ˘˜ ÚˆÙÔ·ıÔ‡˜ ‰ÈËıËÙÈÎ‹˜ ÂÍÂÚÁ·Û›·˜ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ ‰ÂÍÈÔ‡ ËÌÈıˆÚ·Î›Ô˘ ÌÂ ‰È‹ıËÛË ÙË˜ 6Ë˜ Î·È 7Ë˜ ÏÂ˘Ú¿˜ Î·È Â¤ÎÙ·ÛË ÙË˜ Ì¿˙·˜ ÂÓ‰ÔÓÂ˘ÌÔÓÈÎ¿, ‰È‹ıËÛË ÙÔ˘ £-6 ÛÔÓ‰‡ÏÔ˘ Î·È Â¤ÎÙ·ÛË ÂÓ‰ÔÎ·Ó·ÏÈÎ¿ ÛÙÔÓ Ô›ÛıÈÔ ÂÈÛÎÏËÚ›‰ÈÔ ¯ÒÚÔ (£5-£8) (∂ÈÎfiÓ· 4). ∏ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËÎÂ ÛÂ Î·ÙÂ˘ı˘ÓfiÌÂÓË ‚ÈÔ„›· ÌÂ ‚ÂÏfiÓË ·fi ÙËÓ ·Ú·ÛÔÓ‰˘ÏÈÎ‹ Ì¿˙· Ô˘ ·ÔÎ¿Ï˘„Â ÙËÓ ‡·ÚÍË Î·ÎÔ‹ıÔ˘˜ ÓÂÔÏ¿ÛÌ·ÙÔ˜ ·fi ÌÈÎÚ¿ ÛÙÚÔÁÁ˘Ï¿, ÌÏÂ Î‡ÙÙ·Ú· ÌÂ ¯·Ú·ÎÙ‹ÚÂ˜ Û˘Ì‚·ÙÔ‡˜ ÌÂ Û¿ÚÎˆÌ· ÙÔ˘ Ewing/PNET. ∞fi ÙË ÓÂ˘ÚÔÏÔÁÈÎ‹ ·ÓÙÈÎÂÈÌÂÓÈÎ‹ ÂÍ¤Ù·ÛË Ë ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·˙Â ÂÚÈÔÚÈÛÌfi ÙË˜ ·˘ıfiÚÌËÙË˜ ÎÈÓËÙÈÎfiÙËÙ·˜ ÙÔ˘ ‰ÂÍÈÔ‡ Î¿Ùˆ ¿ÎÚÔ˘ (Û¯Â‰fiÓ Ï‹ÚË˜ ·‰˘Ó·Ì›· Ú·¯È·›·˜ Î¿Ì„Ë˜ Î·È ·Ó¤ÁÂÚÛË˜ Î¿Ùˆ ¿ÎÚÔ˘). ªÂÙ¿ ·fi ÓÂ˘ÚÔ¯ÂÈÚÔ˘ÚÁÈÎ‹ ÂÎÙ›ÌËÛË ·ÔÊ·Û›ÛÙËÎÂ Ë ¯ÂÈÚÔ˘ÚÁÈÎ‹ ·Ê·›ÚÂÛË ÙÔ˘ fiÁÎÔ˘ ÌÂ ÛÙfi¯Ô ÙËÓ ·ÔÛ˘Ì›ÂÛË ÙÔ˘ ÓˆÙÈ·›Ô˘ Ì˘ÂÏÔ‡. ªÂÙ¿ ·fi ‰ÂÍÈ¿ ıˆÚ·ÎÔÙÔÌ‹ Ô fiÁÎÔ˜ ÎÚ›ıËÎÂ ·ÓÂÁ¯Â›ÚË¶·È‰È·ÙÚÈÎ‹ 2006;69:458-462

ÙÔ˜ Î·È ÁÈ· ÙÔÓ ÏfiÁÔ ·˘Ùfi ¤ÁÈÓÂ ÌfiÓÔ Ï‹„Ë ˘ÏÈÎÔ‡ ÁÈ· ‚ÈÔ„›· Î·È Û˘ÚÚ·Ê‹ ÙË˜ ÙÔÌ‹˜. ∆Ô fiÚÈÛÌ· ÙË˜ ‚ÈÔ„›·˜ ÂÈ‚Â‚·›ˆÛÂ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ ÂÍˆÔÛÙÈÎÔ‡ Û·ÚÎÒÌ·ÙÔ˜ ÙÔ˘ Ewing, Ë ‰Â ÌÔÚÈ·Î‹ ·Ó¿Ï˘ÛË ·ÔÎ¿Ï˘„Â ÙË ÌÂÙ¿ıÂÛË EWS-FLI-1 [t(11;22) (q24;q12)]. ∏ ·ÛıÂÓ‹˜ ÛÙËÓ ÎÏÈÓÈÎ‹ Ì·˜ ¿Ú¯ÈÛÂ ¯ËÌÂÈÔıÂÚ·Â›· ÌÂ ÂÈ‰ÈÎfi ÚˆÙfiÎÔÏÏÔ ÁÈ· Û¿ÚÎˆÌ· ÙÔ˘ Ewing (IESS NCI) (5). ∏ Î·Ù¿ÛÙ·ÛË ÙË˜ ·ÛıÂÓÔ‡˜ ¤Ó· Ì‹Ó· ·fi ÙËÓ ¤Ó·ÚÍË ÙË˜ ¯ËÌÂÈÔıÂÚ·Â›·˜ ¤‰ÂÈÍÂ Û¯ÂÙÈÎ‹ ‚ÂÏÙ›ˆÛË ÙË˜ ÎÈÓËÙÈÎfiÙËÙ·˜ ÙÔ˘ Î¿Ùˆ ¿ÎÚÔ˘, Ë MRI ÙÔ˘ ıÒÚ·ÎÔ˜ ÂÏ¿ÙÙˆÛË ÙË˜ Ì¿˙·˜ ÙÔ˘ fiÁÎÔ˘ Î·È ˘Ô¯ÒÚËÛË ÙË˜ ›ÂÛË˜ ÙÔ˘ ÓˆÙÈ·›Ô˘ Ì˘ÂÏÔ‡ ÂÓ‰ÔÎ·Ó·ÏÈÎ¿. ∏ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËÎÂ 3 Ì‹ÓÂ˜ ·ÚÁfiÙÂÚ· ÛÂ ·ÎÙÈÓÔıÂÚ·Â›· ÌÂ Û˘ÓÔÏÈÎ‹ ‰fiÛË 40Gy Û‡ÌÊˆÓ· ÌÂ ÙÔ ÚˆÙfiÎÔÏÏÔ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ÛÂ ÂÈÙ˘¯‹ ÔÏÈÎ‹ ·Ê·›ÚÂÛË ÙÔ˘ fiÁÎÔ˘. ŒÎÙÔÙÂ, Ë ·ÛıÂÓ‹˜ ÔÏÔÎÏ‹ÚˆÛÂ ÙÔ ¯ËÌÂÈÔıÂÚ·Â˘ÙÈÎfi Û¯‹Ì· Û˘ÓÔÏÈÎ‹˜ ‰È¿ÚÎÂÈ·˜ 51 Â‚‰ÔÌ¿‰ˆÓ ¯ˆÚ›˜ ˘ÔÙÚÔ‹ ÙË˜ ÓfiÛÔ˘ ‹ ¿ÏÏÂ˜ ÂÈÏÔÎ¤˜ Î·È ‚Ú›ÛÎÂÙ·È ÛÂ ¿ÚÈÛÙË ÎÏÈÓÈÎ‹ Î·Ù¿ÛÙ·ÛË.

™˘˙‹ÙËÛË ∆Ô Û¿ÚÎˆÌ· ÙÔ˘ Ewing ÂÚÈÁÚ¿ÊËÎÂ ÚÒÙË ÊÔÚ¿ ·fi ÙÔÓ James Ewing ÙÔ 1921 ˆ˜ ÔÛÙÂÔÏ˘ÙÈÎ‹ ÂÛÙ›· ÙË˜ ÎÂÚÎ›‰·˜ ÛÂ ÎÔÚ›ÙÛÈ ËÏÈÎ›·˜ 14 ÂÙÒÓ (6). ∏ ÂÍˆÔÛÙÈÎ‹ ÌÔÚÊ‹ ÙÔ˘ Û·ÚÎÒÌ·ÙÔ˜ ÙÔ˘ Ewing ÂÚÈÁÚ¿ÊËÎÂ ÚÒÙË ÊÔÚ¿ ÙÔ 1969 ·fi ÙÔÓ Tefft Î·È Û˘Ó (7). ∆Ô EES ·ÔÙÂÏÂ› ÂÍ·ÈÚÂÙÈÎ¿ Û¿ÓÈÔ Î·È ˘„ËÏ‹˜ Î·ÎÔ‹ıÂÈ·˜ fiÁÎÔ Ô˘ ·ÓÙÈÚÔÛˆÂ‡ÂÈ ÂÚ›Ô˘ ÙÔ 5% ÙˆÓ

∂ÈÎﬁÓ· 4. ª·ÁÓËÙÈÎ‹ ÙÔÌÔÁÚ·Ê›· ıˆÚ·ÎÈÎ‹˜ ÌÔ›Ú·˜ ÛÔÓ‰˘ÏÈÎ‹˜ ÛÙ‹ÏË˜. ∂˘ÌÂÁ¤ıË˜ ‰ÈËıËÙÈÎ‹ ÂÍÂÚÁ·Û›· Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ ‰ÂÍÈÔ‡ ËÌÈıˆÚ·Î›Ô˘ ÌÂ Â¤ÎÙ·ÛË ÂÓ‰ÔıˆÚ·ÎÈÎ¿, ÂÓ‰ÔÛÔÓ‰˘ÏÈÎ¿ Î·È ÂÓ‰ÔÎ·Ó·ÏÈÎ¿ ÛÙÔ ‡„Ô˜ ÙˆÓ £-6 Î·È £-7.

461

¶·Ú·ÛÔÓ‰˘ÏÈÎﬁ ÂÍˆÔÛÙÈÎﬁ Û¿ÚÎˆÌ· ÙÔ˘ Ewing

Û·ÚÎˆÌ¿ÙˆÓ ÙˆÓ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ ÙË˜ ·È‰ÈÎ‹˜ ËÏÈÎ›·˜ (8). ™‡ÌÊˆÓ· ÌÂ ÌÈ· ÚfiÛÊ·ÙË ÌÂÙ·-·Ó¿Ï˘ÛË ÙË˜ ‰ÈÂıÓÔ‡˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ ¤¯Ô˘Ó ÂÚÈÁÚ·ÊÂ› 32 ÂÚÈÙÒÛÂÈ˜ Û·ÚÎˆÌ¿ÙˆÓ PNET/EES ÌÂ ÂÓÙfiÈÛË ·Ú·ÛÔÓ‰˘ÏÈÎ¿ (1). ∞fi ÙÔ˘˜ 32 ·ÛıÂÓÂ›˜ ÔÈ 15 (46,8%) ‹Ù·Ó ËÏÈÎ›·˜ 10-20 ÂÙÒÓ, ÂÓÒ Î·Ù·ÁÚ¿ÊËÎÂ Û˘¯ÓfiÙÂÚ· ÛÂ ¿ÚÚÂÓÂ˜ (22/32, 68,75%). ∏ ÔÛÊ˘·ÏÁ›·, Ë Ú·¯È·ÏÁ›· Î·È Ë ÏÂ˘ÚÔ‰˘Ó›·, fiˆ˜ ·ÎÚÈ‚Ò˜ ·Ó¤ÊÂÚ·Ó Î·È ÔÈ 2 ·ÛıÂÓÂ›˜ Ì·˜, ·ÔÙÂÏÔ‡Ó Ù· Û˘¯ÓfiÙÂÚ· Û˘ÌÙÒÌ·Ù·, ÂÓÒ Ë Ì¤ÛË ‰È¿ÚÎÂÈ· ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Â›Ó·È 5,7 Ì‹ÓÂ˜ (Â‡ÚÔ˜: 4 ËÌ¤ÚÂ˜-18 Ì‹ÓÂ˜) (1,9,10). ∏ ‰È·ÊÔÚÈÎ‹ ‰È¿ÁÓˆÛË ÙˆÓ fiÁÎˆÓ ·fi ÌÈÎÚ¿, ÛÙÚÔÁÁ˘Ï¿, ÌÏÂ Î‡ÙÙ·Ú· Â›Ó·È ‰‡ÛÎÔÏË Î·È ··ÈÙÂ›Ù·È Ë Û˘Ì‚ÔÏ‹ ÙË˜ ÈÛÙÔÏÔÁÈÎ‹˜/·ÓÔÛÔ˚ÛÙÔ¯ËÌÈÎ‹˜ ·Ó¿Ï˘ÛË˜, ÙË˜ ÌÔÚÈ·Î‹˜ ‚ÈÔÏÔÁ›·˜ Î·È ÙÔ˘ ËÏÂÎÙÚÔÓÈÎÔ‡ ÌÈÎÚÔÛÎÔ›Ô˘ ÁÈ· ÙËÓ Â›ÙÂ˘Í‹ ÙË˜ (11,12). ∏ ÂÍ·ÈÚÂÙÈÎ‹ ÚfiÔ‰Ô˜ ÙË˜ Î˘ÙÙ·ÚÔÁÂÓÂÙÈÎ‹˜ Î·È ÙË˜ ÌÔÚÈ·Î‹˜ ‚ÈÔÏÔÁ›·˜ Î·Ù¤ÛÙËÛÂ ‰˘Ó·Ù‹ ÙËÓ ·Ó›¯ÓÂ˘ÛË ¯ÚˆÌÔÛˆÌÈÎÒÓ Î·È ÌÔÚÈ·ÎÒÓ ·Ó·‰È·Ù¿ÍÂˆÓ Ô˘ ÂÈÙÚ¤Ô˘Ó ÙÔÓ Î·ıÔÚÈÛÌfi ·ÎÚÈ‚Ô‡˜ ‰È¿ÁÓˆÛË˜ Î·È ÚfiÁÓˆÛË˜, fiˆ˜ ÛÙÔ˘˜ ·ÛıÂÓÂ›˜ ÙË˜ ÌÂÏ¤ÙË˜ Ì·˜, fiÔ˘ Ë RT-PCR ·ÔÎ¿Ï˘„Â ÙËÓ ·ÚÔ˘Û›· ˘‚ÚÈ‰ÈÎÒÓ ÌÂÙ·ÁÚ·ÊÒÓ EWS-FLI-1 ÙÂÎÌËÚÈÒÓÔÓÙ·˜ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ EES. ™ËÌ·ÓÙÈÎ‹ ÌÂÙ¿ ·fi ÎÏÈÓÈÎÔ·ıÔÏÔÁÈÎ¤˜ ÌÂÏ¤ÙÂ˜ Â›Ó·È Ë ‰È·›ÛÙˆÛË fiÙÈ Ë ÂÌÊ¿ÓÈÛË ÙË˜ ÌÂÙ¿ıÂÛË˜ EWS-FLπ Ù‡Ô˘ 1 Û¯ÂÙ›˙ÂÙ·È ÌÂ Î·Ï‡ÙÂÚË ÔÚÂ›· ÙË˜ ÓfiÛÔ˘ ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ÛÙ¿‰ÈÔ ÙË˜ ÓfiÛÔ˘ Î·Ù¿ ÙË ‰È¿ÁÓˆÛË (13,14). ∞Ó Î·È Ì¤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó ÂÚÈÁÚ·ÊÂ› ÂÚÈÛÛfiÙÂÚ· ·fi 15 ˘‚ÚÈ‰ÈÎ¿ ÌÂÙ·ÁÚ·Ê‹Ì·Ù· ÌÂÙ·ı¤ÛÂˆÓ ÛÙ· EWS, ¤¯ÂÈ ·Ô‰ÂÈ¯ıÂ› fiÙÈ Ù· ¯ÈÌ·ÈÚÈÎ¿ ÁÔÓ›‰È· Ô˘ ÚÔÎ‡ÙÔ˘Ó Â›Ó·È ˘Â‡ı˘Ó· ÁÈ· ÙËÓ ·Ú·ÁˆÁ‹ ·ÚfiÌÔÈˆÓ ÚˆÙÂ˚ÓÒÓ, ÌÂ ·ÔÙ¤ÏÂÛÌ· Ô ÚfiÏÔ˜ ÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ÌÂÙ·ı¤ÛÂˆÓ Ó· Â›Ó·È ·ÓÂÍ¿ÚÙËÙÔ˜ ÙË˜ ÔÁÎÔÁÔÓÈÎ‹˜ Û˘ÌÂÚÈÊÔÚ¿˜

ÙˆÓ fiÁÎˆÓ ÙË˜ ÔÌ¿‰·˜ ·˘Ù‹˜. ∂ÓÙÔ‡ÙÔÈ˜, Û‡ÌÊˆÓ· ÌÂ ÚfiÛÊ·ÙÂ˜ ÌÂÏ¤ÙÂ˜ ¤¯ÂÈ ·Ô‰ÂÈ¯ıÂ› fiÙÈ ÔÈ ‰È·ÊÔÚÂÙÈÎ¤˜ ·ÓÙÈÌÂÙ·ı¤ÛÂÈ˜ Û¯ÂÙ›˙ÔÓÙ·È ÌÂ ÙËÓ ÎÏÈÓÈÎ‹ ÔÚÂ›· Î·È ÂÍ¤ÏÈÍË ÙˆÓ fiÁÎˆÓ ·˘ÙÒÓ (15). ™ÙÔÓ ¶›Ó·Î· 1 ·Ó·Ê¤ÚÔÓÙ·È ÔÈ Û˘¯ÓfiÙÂÚÂ˜ ¯ÚˆÌÔÛˆÌÈÎ¤˜ ÌÂÙ·ı¤ÛÂÈ˜ ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ ÙˆÓ Û·ÚÎˆÌ¿ÙˆÓ ÙÔ˘ Ewing (Ewing Sarcoma family tumors, ESFT). H ¯Ú‹ÛË Û‹ÌÂÚ· Ó¤ˆÓ ÂÍÂÈ‰ÈÎÂ˘Ì¤ÓˆÓ ÌÂıfi‰ˆÓ fiˆ˜ Â›Ó·È Ë RT-PCR Î·È Ë Ì¤ıÔ‰Ô˜ FISH ÙÂÎÌËÚÈÒÓÔ˘Ó ÙË ‰È¿ÁÓˆÛË ÛÂ Ú·ÁÌ·ÙÈÎ¿ ‰‡ÛÎÔÏÂ˜ ÂÚÈÙÒÛÂÈ˜, fiÔ˘ ÎÏÈÓÈÎÔÂÚÁ·ÛÙËÚÈ·Î¿ Â˘Ú‹Ì·Ù· ı¤ÙÔ˘Ó ¤ÓÙÔÓË ÙËÓ ˘Ô„›·, ·ÏÏ¿ ‰ÂÓ Â·ÚÎÔ‡Ó ÁÈ· Ó· ‚Â‚·ÈÒÛÔ˘Ó ÌÂ ·ÎÚ›‚ÂÈ· ÙË ‰È¿ÁÓˆÛË Û·ÚÎÒÌ·ÙÔ˜ ÙÔ˘ Ewing. ∂ÈÏ¤ÔÓ, Ë RT-PCR Â›Ó·È ¯Ú‹ÛÈÌË Ì¤ıÔ‰Ô˜ ÁÈ· ÙËÓ ·Ó›¯ÓÂ˘ÛË ˘ÔÏÂÈfiÌÂÓË˜ ÓfiÛÔ˘ ‹ ÚÒÈÌË˜ ˘ÔÙÚÔ‹˜ ÛÙÔ ¿ÌÂÛÔ Ì¤ÏÏÔÓ (12). √ Û˘Ó‰˘·ÛÌfi˜ ¯ËÌÂÈÔ-, ·ÎÙÈÓÔıÂÚ·Â›·˜ Î·È ¯ÂÈÚÔ˘ÚÁÈÎ‹˜ ·Ê·›ÚÂÛË˜ ÙÔ˘ fiÁÎÔ˘ ÚÔÛÊ¤ÚÂÈ ÙËÓ Î·Ï‡ÙÂÚË ÂÏÂ‡ıÂÚË ÓfiÛÔ˘ ÂÈ‚›ˆÛË (event free survival, EFS) Î·È Û˘ÓÔÏÈÎ‹ ÂÈ‚›ˆÛË (overall survival, OS) ÙˆÓ ·ÛıÂÓÒÓ. ™‡ÌÊˆÓ· ÌÂ ÓÂfiÙÂÚ· ‚È‚ÏÈÔÁÚ·ÊÈÎ¿ ‰Â‰ÔÌ¤Ó·, Î·Ù·ÁÚ¿ÊÔÓÙ·È Û‹ÌÂÚ· ˘„ËÏfiÙÂÚ· ÔÛÔÛÙ¿ ÂÈ‚›ˆÛË˜ fiÙ·Ó Ë ¯ÂÈÚÔ˘ÚÁÈÎ‹ ·Ê·›ÚÂÛË ÚÔËÁÂ›Ù·È ÙË˜ ¯ËÌÂÈÔıÂÚ·Â›·˜, fiˆ˜ ÛÙÔÓ ÚÒÙÔ ·ÛıÂÓ‹ ÙË˜ ÌÂÏ¤ÙË˜ Ì·˜. ∞fi ÔÏ˘ÎÂÓÙÚÈÎ¤˜ ÌÂÏ¤ÙÂ˜ ÚÔÎ‡ÙÂÈ fiÙÈ Ë 5ÂÙ‹˜ EFS ·Ó¤Ú¯ÂÙ·È ÛÙÔ 61% ÁÈ· ·ÛıÂÓÂ›˜ ÌÂ EES Ô˘ ·ÓÙÈÌÂÙˆ›ÛıËÎ·Ó ÌÂ Û˘Ó‰˘·ÛÌfi ¯ËÌÂÈÔ-, ·ÎÙÈÓÔıÂÚ·Â›·˜ Î·È ¯ÂÈÚÔ˘ÚÁÈÎ‹˜ ·Ê·›ÚÂÛË˜, fiÌˆ˜, Ë ÂÓÙfiÈÛË ÙË˜ Ì¿˙·˜ ·Ú·ÛÔÓ‰˘ÏÈÎ¿ Û¯ÂÙ›˙ÂÙ·È ÌÂ ÌÈÎÚfiÙÂÚË ÂÈ‚›ˆÛË (37,5%) (5,12,16). ∆¤ÏÔ˜, ÚÔÎ‡ÙÂÈ fiÙÈ Ë ÌÈÎÚ‹ Ì¿˙· ÙÔ˘ fiÁÎÔ˘, Ë Â˘ÚÂ›· ¯ÂÈÚÔ˘ÚÁÈÎ‹ ·Ê·›ÚÂÛ‹ ÙÔ˘ Î·È Ë ·Ô˘Û›· ÌÂÙ·ÛÙ¿ÛÂˆÓ Î·Ù¿ ÙË ‰È¿ÁÓˆÛË ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎÔ‡˜ Â˘ÓÔ˚ÎÔ‡˜ ÚÔÁÓˆÛÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙÂ˜ (4,16). ™˘ÌÂÚ·ÛÌ·ÙÈÎ¿, ÚÔÎ‡ÙÂÈ fiÙÈ ÙÔ EES, ·ÚfiÙÈ Û¿ÓÈÔ, ı· Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È

¶›Ó·Î·˜ 1. ™˘¯ÓﬁÙÂÚÂ˜ ¯ÚˆÌÔÛˆÌÈÎ¤˜ ÌÂÙ·ı¤ÛÂÈ˜ ÙË˜ ÔÈÎÔÁ¤ÓÂÈ·˜ ÙˆÓ Û·ÚÎˆÌ¿ÙˆÓ ÙÔ˘ Ewing (Ewing’s Sarcoma family tumors, ESFT). ªÂÙ¿ıÂÛË

ÃÚˆÌÔÛˆÌÈÎ‹ ·ÓˆÌ·Ï›·

™˘¯ÓﬁÙËÙ·

EWS-FLI-1

t(11;22)(q12;q24)

90-95%

∆‡Ô˘ 1 ∆‡Ô˘ 2 16 ¿ÏÏÔÈ Ù‡ÔÈ ÌÂÙ·ÁÚ·ÊÒÓ EWS-ERG ∆‡Ô˘ 1 4 ¿ÏÏÔÈ Ù‡ÔÈ ÌÂÙ·ÁÚ·ÊÒÓ EWS-ETV1 EWS-EIAF EWS-FEV

t(21;22)(q22;q12)

t(7;22)(p22;q12) t(17;22)(q12;q12) t(2;22)(q33;q12)

(65%) (20%) (15%) 5-10% (60%) (40%) <1% <1% <1% ¶·È‰È·ÙÚÈÎ‹ 2006;69:458-462

462

º. ∞ı·Ó·ÛÈ¿‰Ô˘ Î·È Û˘Ó.

ÛÙË ‰È·ÊÔÚÈÎ‹ ‰È¿ÁÓˆÛË ÙˆÓ fiÁÎˆÓ ÙˆÓ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ ÙË˜ ·Ú·ÛÔÓ‰˘ÏÈÎ‹˜ ÂÚÈÔ¯‹˜, ÒÛÙÂ Ó· Î·Ù·ÛÙÂ› ‰˘Ó·Ù‹ Ë ¤ÁÎ·ÈÚË ‰È¿ÁÓˆÛË Î·È ¤Ó·ÚÍË ÙË˜ ıÂÚ·Â˘ÙÈÎ‹˜ ·ÁˆÁ‹˜. ∂ÈÏ¤ÔÓ, Ô ÁÂÓÈÎfi˜ ·È‰›·ÙÚÔ˜ ı· Ú¤ÂÈ Ó· Â›Ó·È È‰È·›ÙÂÚ· Â˘·ÈÛıËÙÔÔÈËÌ¤ÓÔ˜ fiÙ·Ó ·ÓÙÈÌÂÙˆ›˙ÂÈ ÂÊ‹‚Ô˘˜ Î·È ÓÂ·ÚÔ‡˜ ÂÓ‹ÏÈÎÂ˜ ÌÂ Â›ÌÔÓÔ fiÓÔ ÛÙ· ÔÛÙ¿ ‹ ÛÙ· Ì·Ï·Î¿ ÌfiÚÈ·, ÒÛÙÂ ¤ÁÎ·ÈÚ· Ó· Î·Ù·ÊÂ‡ÁÂÈ ÛÂ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Harimaya K, Oda Y, Matsuda S, Tanaka K, Chuman H, Iwamoto Y. Primitive neuroectodermal tumor and extraskeletal Ewing sarcoma arising primarily around the spinal column: report of four cases and a review of the literature. Spine 2003; 28:408-412. 2. Eroglu A, Kurkcuoglu IC, Karaoglanoglu N, Alper F, Gundogdu C. Extraskeletal Ewing sarcoma of the diaphragm presenting with hemothorax. Ann Thorac Surg 2004;78:715-717. 3. Shin JH, Lee HK, Rhim SC, Cho KJ, Choi CG, Suh DC. Spinal epidural extraskeletal Ewing sarcoma: MR findings in two cases. AJNR Am J Neuroradiol 2001;22:795-798. 4. Kutluk MT, Yalcin B, Akyuz C, Varan A, Ruacan S, Buyukpamukcu M. Treatment results and prognostic factors in Ewing sarcoma. Pediatr Hematol Oncol 2004; 21:597-610. 5. Grier H, Krailo M, Link M et al. Improved outcome in non-metastatic Ewing’s sarcoma (EWS) and PNET of bone with the addition of ifosfamide (I) and etoposide (E) to vincristine (V), Adriamycin (Ad), cyclophosphamide (C), and Actinomycin (A): a Children’s Cancer Group (CCG) and Pediatric Oncology Group (POG) report. Proc Am Soc Clin Oncol 1994;13:421.

¶·È‰È·ÙÚÈÎ‹ 2006;69:458-462

6. Ewing J. Diffuse endothelioma of bone. Proc NY Pathol Soc 1921;21;17:1-13. 7. Tefft M, Vawter GM, Mitus A. Paravertebral “round cell” tumors in children. Radiology 1969;92:15011509. 8. Raney RB, Asmar L, Newton WA Jr, Bagwell C, Breneman JC, Crist W, et al. Ewing’s sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991. J Clin Oncol 1997;15:574-582. 9. Medrano Martin MC, Alvarez Guisasola FJ, Alvarez Gago T, Valbuena Crespo C, Blanco Quiros A, Bobillo del Amo H. Extraskeletal Ewing sarcoma. Report of a new case and revision of the subject. An Esp Pediatr 1992;36:487-490. 10. O'Keeffe F, Lorigan JG, Wallace S. Radiological features of extraskeletal Ewing sarcoma. Br J Radiol 1990;63:456-460. 11. Guiter GE, Gamboni MM, Zakowski MF. The cytology of extraskeletal Ewing sarcoma. Cancer 1999;87:141-148. 12. Ahmad R, Mayol BR, Davis M, Rougraff BT. Extraskeletal Ewing’s sarcoma. Cancer 1999; 85:725-731. 13. De Alava E, Kawai A, Healey JH, Fligman I, Meyers PA, Huvos AG, et al. EWS-FLI-1 fusion transcript structure is an independent determinant of prognosis in Ewing’s sarcoma. J Clin Oncol 1998;16:12481255. 14. De Alava E, Panizo A, Antonescu CR, Huvos AG, Pardo-Mindan FJ, Barr FG, et al. Association of EWSFLI-1 type 1 fusion with lower proliferative rate in Ewing’s sarcoma. Am J Pathol 2000;156:849-855. 15. Delattre O, Zucman J, Melot T, Garau XS, Zucker JM, Lenoir GM, et al. The Ewing family of tumors a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 1994; 331:294-299. 16. Koscielniak E, Morgan M, Treuner J. Soft tissue sarcoma in children: prognosis and management. Paediatr Drugs 2002; 4:21-28.

∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏

CASE REPORT

463

°ÂÓÓ‹ÛÂÈ˜ ·È‰ÈÒÓ ÌÂ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜ ÌÂÙ¿ ·ﬁ ˘Ô‚ÔËıÔ‡ÌÂÓË ÁÔÓÈÌÔÔ›ËÛË π. ∆Û¿ÙÚ·1, ∫. ∫·Ú·ÛÌ¿ÓË˜1, º. µ·ÚÂÏ¿˜2, X. ∆Û¿ÓÙ·ÏË1, A. ∫Ô‡ÛË1, M. ∞ı·Ó·Û›Ô˘1

¶ÂÚ›ÏË„Ë: ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ÌÂ ÙË ÌÂÁ¿ÏË ÚfiÔ‰Ô ÙˆÓ ÙÂ¯ÓÈÎÒÓ ˘Ô‚ÔËıÔ‡ÌÂÓË˜ ·Ó··Ú·ÁˆÁ‹˜, fiÏÔ Î·È ÂÚÈÛÛfiÙÂÚ· ˙Â˘Á¿ÚÈ· ÌÂ ÚÔ‚Ï‹Ì·Ù· ÁÔÓÈÌfiÙËÙ·˜ Î·Ù·ÊÂ‡ÁÔ˘Ó ÛÂ ·˘Ù¤˜. ¶·Ú¿ÏÏËÏ·, Ù· ÚÔÁÚ¿ÌÌ·Ù· ÚfiÏË„Ë˜ ÙË˜ ‚-ªÂÛÔÁÂÈ·Î‹˜ ∞Ó·ÈÌ›·˜ (‚-ª∞) ¤¯Ô˘Ó ÂÙ‡¯ÂÈ ÙÔÓ ÛÙfi¯Ô ÙÔ˘˜, ÌÂÈÒÓÔÓÙ·˜ ‰Ú·ÛÙÈÎ¿ ÙÔÓ ·ÚÈıÌfi ÁÂÓÓ‹ÛÂˆÓ Ó¤ˆÓ ·Û¯fiÓÙˆÓ. øÛÙfiÛÔ, ·Ú·ÙËÚÔ‡ÓÙ·È ÁÂÓÓ‹ÛÂÈ˜ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞ Î·È ¿ÏÏÂ˜ ÛÔ‚·Ú¤˜ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜ ÌÂÙ¿ ·fi ¯Ú‹ÛË ÌÂıfi‰ˆÓ ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜. ¶ÂÚÈÁÚ¿ÊÔÓÙ·È ÙÚÂÈ˜ ÂÚÈÙÒÛÂÈ˜ ÁÂÓÓ‹ÛÂˆÓ ·ÛıÂÓÒÓ ÌÂ ÛÔ‚·Ú¤˜ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜ Ô˘ ÚÔ‹Ïı·Ó ·fi ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË. √ ÚÒÙÔ˜ ·ÛıÂÓ‹˜ ÂÌÊ·Ó›˙ÂÈ ÔÌfi˙˘ÁÔ ‚-ª∞ ÌÂÙ¿ ·fi ¯Ú‹ÛË ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘, Ô ‰Â‡ÙÂÚÔ˜ ‰ÈÏ‹ ÂÙÂÚÔ˙˘ÁˆÙ›· ‰ÚÂ·ÓÔÎ˘ÙÙ·ÚÈÎ‹˜ ÓfiÛÔ˘ Î·È ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈ·˜ D (D-Punjab) ÌÂÙ¿ ·fi ¯Ú‹ÛË ˆ·Ú›Ô˘ ‰fiÙÚÈ·˜ Î·È Ô ÙÚ›ÙÔ˜ ‰ÈÏ‹ ÂÙÂÚÔ˙˘ÁˆÙ›· ‚-ª∞ Î·È ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈ·˜ Lepore ÌÂÙ¿ ·fi ¯Ú‹ÛË Û¤ÚÌ·ÙÔ˜ ‰fiÙË. √È ¿Û¯ÔÓÙÂ˜ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È Û˘ÛÙËÌ·ÙÈÎ¿ Î·È ˘Ô‚¿ÏÏÔÓÙ·È ÛÂ ıÂÚ·Â›· ÛÙË ªÔÓ¿‰· ªÂÛÔÁÂÈ·Î‹˜ ∞Ó·ÈÌ›·˜. ™ÙËÓ ∂ÏÏ¿‰· Û‹ÌÂÚ·, ·Ú¿ ÙËÓ Â˘ÚÂ›· ¯Ú‹ÛË ÙˆÓ ÙÂ¯ÓÈÎÒÓ ˘Ô‚ÔËıÔ‡ÌÂÓË˜ ·Ó··Ú·ÁˆÁ‹˜, ‰ÂÓ ˘¿Ú¯Ô˘Ó Û·ÊÒ˜ ıÂÛÌÔıÂÙËÌ¤ÓÔÈ Î·ÓfiÓÂ˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ Î¤ÓÙÚˆÓ ÂÍˆÛˆÌ·ÙÈÎ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ Î·È ¯Ú‹ÛË˜ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡. ∞ÔÙ¤ÏÂÛÌ· Â›Ó·È Ë ÂÌÊ¿ÓÈÛË ÛÔ‚·ÚÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ ÛÙË ‰ËÌfiÛÈ· ˘ÁÂ›·, fiˆ˜ ·˘Ù¿ Ô˘ ÂÚÈÁÚ¿ÊÔÓÙ·È ÛÙÔ ·ÚfiÓ ¿ÚıÚÔ, ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ÙˆÓ ÔÔ›ˆÓ Â›Ó·È ÂÈÙ·ÎÙÈÎ‹ ·Ó¿ÁÎË Ó· Á›ÓÔ˘Ó ÔÈ ·Ó¿ÏÔÁÂ˜ ÓÔÌÔıÂÙÈÎ¤˜ Ú˘ıÌ›ÛÂÈ˜ Ô˘ ı· Î·ıÔÚ›ÛÔ˘Ó ÌÂ Û·Ê‹ÓÂÈ· ÙÔÓ ÙÚfiÔ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ Î¤ÓÙÚˆÓ ÂÍˆÛˆÌ·ÙÈÎ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ Î·È ı· ÔÚ›ÛÔ˘Ó ÙÔ˘˜ Î·Ù¿ÏÏËÏÔ˘˜ ÌË¯·ÓÈÛÌÔ‡˜ ÂÏ¤Á¯Ô˘.

1 ªÔÓ¿‰· ªÂÛÔÁÂÈ·Î‹˜ ∞Ó·ÈÌ›·˜, ∞’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ∞.¶.£., πÔÎÚ¿ÙÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô, £ÂÛÛ·ÏÔÓ›ÎË 2 ¢’ °˘Ó·ÈÎÔÏÔÁÈÎ‹ª·ÈÂ˘ÙÈÎ‹ ∫ÏÈÓÈÎ‹ ∞.¶.£., πÔÎÚ¿ÙÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô, £ÂÛÛ·ÏÔÓ›ÎË AÏÏËÏÔÁÚ·Ê›·: ªÈÚ¿ÓÙ· ∞ı·Ó·Û›Ô˘-ªÂÙ·Í¿ ªÔÓ¿‰· ªÂÛÔÁÂÈ·Î‹˜ ∞Ó·ÈÌ›·˜, ∞’ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ∞.¶.£. πÔÎÚ¿ÙÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô £ÂÛ/Ó›ÎË˜ ∂-mail: miranda@med.auth.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 04-03-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 22-07-2005

§¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ∂ÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË, ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜.

Births of children with hemoglobinopathies following use of IVF I. Tsatra1, K. Karasmanis1, F. Varelas2, C. Tsantali1, A. Koussi1, M. Athanassiou1

Abstract: Recent advances in techniques of artificial reproduction have lead to their use by constantly increasing numbers of couples with fertility problems. Although ‚-thalassaemia screening programmes have successfully reduced births of affected individuals a number of births have been reported of children with ‚-thalassaemia and other major haemoglobinopathies following in vitro fertilization (IVF). The cases are described of three children with ‚-thalassaemia and other major haemoglobinopathies conceived by IVF. The first child was born with homozygous ‚-thalassaemia after the use of gametes from both parents, the second was a carrier of both sickle cell anaemia and haemoglobinopathy D (D-Punjab) trait after the use of donor ova, and the third was a carrier of both ‚-thalassaemia and haemoglobinopathy Lepore trait after the use of donor sperm. All the patients are being systematically monitored and treated in the Thalassaemia Unit. In Greece at present, despite the increasing use of artificial reproduction techniques, no rules have yet been defined regulating infertility centres and the use of human gametes. The appropriate legal framework needs to be set up for licensing, providing working guidelines and monitoring infertility centres where IVF is provided. Key words: In vitro fertilization (IVF), haemoglobinopathies.

™˘ÓÙÔÌÔÁÚ·Ê›Â˜ ª∞ IVF/ET

ªÂÛÔÁÂÈ·Î‹ ∞Ó·ÈÌ›· ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË Î·È ÂÌ‚Ú˘ÔÌÂÙ·ÊÔÚ¿

GIFT ZIFT ICSI CVS

1 Beta-Thalassaemia Unit, 1st Paediatric Clinic, Aristotle University of Thessaloniki, Ippokration General Hospital of Thessaloniki 2 4th Clinic of GynecologyObstetrics, Aristotle University of Thessaloniki, Ippokration General Hospital of Thessaloniki Correspondence: Miranda Athanassiou-Metaxa Beta-Thalassaemia Unit, 1st Paediatric Clinic, Aristotle University of Thessaloniki, Ippokration General Hospital of Thessaloniki ∂-mail: miranda@med.auth.gr Date of submission: 04-03-2005 Date of approval: 22-07-2005

ÂÓ‰ÔÛ·ÏÈÁÁÈÎ‹ ÌÂÙ·ÊÔÚ¿ Á·ÌÂÙÒÓ ÂÓ‰ÔÛ·ÏÈÁÁÈÎ‹ ÌÂÙ·ÊÔÚ¿ ˙˘ÁˆÙÒÓ ÂÓ‰ÔÎ˘ÙÙ·ÚÔÏ·ÛÌÈÎ‹/ÂÓ‰Ôˆ·ÚÈÎ‹ ¤Á¯˘ÛË ÛÂÚÌ·ÙÔ˙ˆ·Ú›Ô˘ ‚ÈÔ„›· ¯ÔÚÈ·ÎÒÓ Ï·¯ÓÒÓ ¶·È‰È·ÙÚÈÎ‹ 2006;69:463-467

464

π. ∆Û¿ÙÚ· Î·È Û˘Ó.

∂ÈÛ·ÁˆÁ‹

¶ÂÚÈÁÚ·Ê‹ ÂÚÈÛÙ·ÙÈÎÒÓ

∏ ªÂÛÔÁÂÈ·Î‹ ∞Ó·ÈÌ›· (ª∞) Â›Ó·È ÌÈ· ÂÙÂÚÔÁÂÓ‹˜ ÔÌ¿‰· ÁÂÓÂÙÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÛÙ· ÔÔ›· Ë ·Ú·ÁˆÁ‹ Ê˘ÛÈÔÏÔÁÈÎ‹˜ ·ÈÌÔÛÊ·ÈÚ›ÓË˜ Â›Ó·È ÂÓ Ì¤ÚÂÈ ‹ ÙÂÏÂ›ˆ˜ ·ÓÂ·ÚÎ‹˜ ÏfiÁˆ ÙË˜ ÂÏ·ÙÙˆÌ·ÙÈÎ‹˜ Û‡ÓıÂÛË˜ Ì›·˜ ‹ ÂÚÈÛÛÔÙ¤ÚˆÓ ·Ï‡ÛˆÓ ÛÊ·ÈÚ›ÓË˜. ∞Ó¿ÏÔÁ· ÌÂ ÙÈ˜ ·Ï‡ÛÔ˘˜ (· ‹ ‚) Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ÂÏ·ÙÙˆÌ·ÙÈÎ‹ Û‡ÓıÂÛË ¤¯Ô˘Ó ÂÚÈÁÚ·ÊÂ› ‰È¿ÊÔÚ· ı·Ï·ÛÛ·ÈÌÈÎ¿ Û‡Ó‰ÚÔÌ·. √È ÊÔÚÂ›˜ ÙË˜ ‚-ª∞ ÛÙËÓ ∂ÏÏ¿‰· ·Ó¤Ú¯ÔÓÙ·È ÛÙÔ 7,5% Â› ÙÔ˘ ÁÂÓÈÎÔ‡ ÏËı˘ÛÌÔ‡ (1). ∞˘Ùfi ¤¯ÂÈ ˆ˜ Û˘Ó¤ÂÈ· ÙË ‰È·ÈÒÓÈÛË ÙË˜ ÓfiÛÔ˘, È‰È·›ÙÂÚ· ·Ó ‰ÂÓ ÏËÊıÔ‡Ó Ù· Î·Ù¿ÏÏËÏ· Ì¤ÙÚ· ÚfiÏË„Ë˜. ∞fi ÙÔ 1978, ÌÂ ÚˆÙÔ‚Ô˘Ï›· ÙË˜ ¶·ÁÎfiÛÌÈ·˜ √ÚÁ¿ÓˆÛË˜ ÀÁÂ›·˜ (¶.√.À.), ÂÊ·ÚÌfi˙ÂÙ·È Ô ÚÔÁÂÓÓËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ (1). ŒÙÛÈ, ÂÓÒ ·Ï·ÈfiÙÂÚ· ÔÈ ÁÂÓÓ‹ÛÂÈ˜ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞ ·Ó¤Ú¯ÔÓÙ·Ó ÛÂ 200 ÂÙËÛ›ˆ˜, Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Ô ·ÚÈıÌfi˜ ·˘Ùfi˜ ÌÂÈÒıËÎÂ ÛÂ ÏÈÁfiÙÂÚÂ˜ ·fi 10. ™‡ÌÊˆÓ· ÌÂ Ù· ·ÓˆÙ¤Úˆ, ÙÔ ÚfiÁÚ·ÌÌ· ÚfiÏË„Ë˜ ÂÓ ÔÏÏÔ›˜ ¤¯ÂÈ ÂÙ‡¯ÂÈ. øÛÙfiÛÔ, ÙÂÏÂ˘Ù·›· ÌÂ ÙÈ˜ Ó¤Â˜ ÙÂ¯ÓÈÎ¤˜ ˘Ô‚ÔËıÔ‡ÌÂÓË˜ ÁÔÓÈÌÔÔ›ËÛË˜, ¤¯Ô˘Ó ·Ú·ÙËÚËıÂ› ÁÂÓÓ‹ÛÂÈ˜ ·È‰ÈÒÓ ÌÂ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜. ™ÙË ªÔÓ¿‰· ªÂÛÔÁÂÈ·Î‹˜ ∞Ó·ÈÌ›·˜ ÙÔ˘ πÔÎÚ¿ÙÂÈÔ˘ ¡ÔÛÔÎÔÌÂ›Ô˘ £ÂÛÛ·ÏÔÓ›ÎË˜ ‰È·ÁÓÒÛÙËÎ·Ó ÙÚ›· ·È‰È¿ ÌÂ ÛÔ‚·Ú¤˜ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜ Ô˘ ¤¯Ô˘Ó ÁÂÓÓËıÂ› ÌÂÙ¿ ·fi ÙÂ¯ÓËÙ‹ ÁÔÓÈÌÔÔ›ËÛË ÌÂ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÙˆÓ ÁÔÓ¤ˆÓ ‹ Ï‹„Ë ·˘ÙÔ‡ (Û¤ÚÌ·/ˆ¿ÚÈÔ) ·fi ÙÚ¿Â˙Â˜.

1Ô ÂÚÈÛÙ·ÙÈÎfi ∫ÔÚ›ÙÛÈ 2 ÂÙÒÓ, ·ÔÙ¤ÏÂÛÌ· ‰›‰˘ÌË˜ Î‡ËÛË˜ ÌÂÙ¿ ·fi ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË. ∏ ÌËÙ¤Ú· ÁÓˆÛÙ‹ ÊÔÚ¤·˜ ‚-ª∞ (Î·Ù·ÁˆÁ‹ ·fi ÂÚÈÔ¯‹ ÙË˜ Ã·ÏÎÈ‰ÈÎ‹˜), ÂÓÒ Ô ·Ù¤Ú·˜ ·Ó·Ê¤ÚÂÈ fiÙÈ ‰ÂÓ Â›Ó·È ÊÔÚ¤·˜ ‚-ª∞. √È ÁÔÓÂ›˜ ÌÂÙ¿ ·fi ÌÂÚÈÎ¿ ¯ÚfiÓÈ· ¯ˆÚ›˜ Ê˘ÛÈÔÏÔÁÈÎ‹ ÙÂÎÓÔÔ›ËÛË ÛÙÚ¿ÊËÎ·Ó ÛÙËÓ ÙÂ¯ÓËÙ‹. ⁄ÛÙÂÚ· ·fi 3 ¯ÚfiÓÈ· ÚÔÛ·ıÂÈÒÓ ¤ÁÈÓÂ ÂÈÙ˘¯ËÌ¤ÓË ·fiÂÈÚ· ˘Ô‚ÔËıÔ‡ÌÂÓË˜ ÁÔÓÈÌÔÔ›ËÛË˜. ŒÁÈÓÂ ÚfiÎÏËÛË ˆÔı˘Ï·ÎÈÔÚÚËÍ›·˜, ·ÎÔÏÔ‡ıËÛÂ ˆÔÏË„›·, in vitro ÁÔÓÈÌÔÔ›ËÛË ÌÂ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÙÔ˘ Û˘˙‡ÁÔ˘ Î·È ÂÌ‚Ú˘ÔÌÂÙ·ÊÔÚ¿. ¶·Ú¿ÏÏËÏ·, ·Ó·Ê¤ÚÂÙ·È fiÙÈ ¤ÁÈÓÂ Ï‹ÚË˜ ÚÔÁÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ -Î·È ÙÔ˘ ·Ù¤Ú·- Ô ÔÔ›Ô˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ∆Ô ·È‰› ÁÂÓÓ‹ıËÎÂ ÙËÓ 34Ë Â‚‰ÔÌ¿‰· Î‡ËÛË˜ ÌÂ Î·ÈÛ·ÚÈÎ‹ ÙÔÌ‹ Î·È ÓÔÛËÏÂ‡ıËÎÂ ÁÈ· 10 ËÌ¤ÚÂ˜ ÛÂ ÙÌ‹Ì· ÚÔÒÚˆÓ ÏfiÁˆ ÚÔˆÚfiÙËÙ·˜ Î·È ›ÎÙÂÚÔ˘. ™Â ËÏÈÎ›· 5 ÌËÓÒÓ ·ÚÔ˘Û›·ÛÂ ˘ÓËÏ›·, Â‡ÎÔÏË ÎfiˆÛË Î·Ù¿ ÙË Û›ÙÈÛË Î·È ˆ¯ÚfiÙËÙ·. √ ·Ú¯ÈÎfi˜ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜, ¤‰ÂÈÍÂ ÛÔ‚·Ú‹ ·Ó·ÈÌ›· (Ht~18%) Î·È ÙÔ ‚Ú¤ÊÔ˜ ·Ú·¤ÌÊıËÎÂ ÛÙÔ ∞ÈÌ·ÙÔÏÔÁÈÎfi ∂ÍˆÙÂÚÈÎfi π·ÙÚÂ›Ô. ™ÙËÓ ÎÏÈÓÈÎ‹ ÂÍ¤Ù·ÛË ÙÔ ·È‰› ÂÌÊ¿ÓÈ˙Â ˆ¯ÚfiÙËÙ·, ‹·Ú „ËÏ·ÊËÙfi 2-3 cm, ÛÏ‹Ó· „ËÏ·ÊËÙfi 2-3 cm. √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÙˆÓ ÁÔÓ¤ˆÓ Î·È ÙÔ˘ ‚Ú¤ÊÔ˘˜ (¶›Ó·Î·˜ 1) ¤‰ÂÈÍÂ fiÙÈ ÙÔ ‚Ú¤ÊÔ˜ ‹Ù·Ó ÔÌÔ˙˘ÁÒÙË˜ ÁÈ· ‚-ª∞. ∆Ô ‚Ú¤ÊÔ˜ Ù¤ıËÎÂ ÛÂ Ù·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ·ÁÁ›ÛÂˆÓ.

¶›Ó·Î·˜ 1. ∂ÚÁ·ÛÙËÚÈ·Î¿ Â˘Ú‹Ì·Ù· ÔÈÎÔÁ¤ÓÂÈ·˜ 1Ô˘ ÂÚÈÛÙ·ÙÈÎÔ‡ ¶¿Û¯Ô˘Û· Hb (g/dl) Ht (%) MCV (fl) MCH (pg) ªÔÚÊÔÏÔÁ›· ÂÚ˘ıÚÒÓ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜

ºÂÚÚÈÙ›ÓË (ng/ml) ∞ÈÌÔÂÙ¿ÏÈ· (x 103/Ìl) ∏b A2 Hb F ªÂÙ·ÏÏ·Á¤˜ ÁÔÓÈ‰›Ô˘ ‚ ·Ï‡ÛÔ˘ ¶·È‰È·ÙÚÈÎ‹ 2006;69:463-467

¶·Ù¤Ú·˜

ªËÙ¤Ú·

9,6

12,9

11,2

29,5 79,3 25,8 ∞ÓÈÛÔÎ˘ÙÙ¿ÚˆÛË ++ ªÈÎÚÔÎ˘ÙÙ¿ÚˆÛË ++ ¶ÔÈÎÈÏÔÎ˘ÙÙ¿ÚˆÛË ++ ÀÔ¯ÚˆÌ›· + ∂Ú˘ıÚÔ‚Ï¿ÛÙÂ˜ Û¿ÓÈÔÈ ¢ÈÏﬁ˜ ÏËı˘ÛÌﬁ˜ 459 229.000 2,6% 40% IVS1:110 / CD39

41,8 63 19,5 ∞ÓÈÛÔÎ˘ÙÙ¿ÚˆÛË + ¶ÔÈÎÈÏÔÎ˘ÙÙ¿ÚˆÛË+ ÀÔ¯ÚˆÌ›· + µ. ÛÙ›ÍË +

33,3 68,4 21,1 ∞ÓÈÛÔÎ˘ÙÙ¿ÚˆÛË + ¶ÔÈÎÈÏÔÎ˘ÙÙ¿ÚˆÛË+ ÀÔ¯ÚˆÌ›· + µ. ÛÙ›ÍË +

148 177.000 6,4% 0,5% N / CD39

30 295.000 5,8% 1% IVS1:110 / N

465

∞ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜ ÌÂÙ¿ ·ﬁ ˘Ô‚ÔËıÔ‡ÌÂÓË ÁÔÓÈÌÔÔ›ËÛË

2Ô ÂÚÈÛÙ·ÙÈÎfi ∞ÁfiÚÈ ËÏÈÎ›·˜ 5 ÂÙÒÓ, ·ÔÙ¤ÏÂÛÌ· ‰›‰˘ÌË˜ Î‡ËÛË˜ ÌÂÙ¿ ·fi ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË ÌÂ ¯Ú‹ÛË ‰fiÙÚÈ·˜ ˆ·Ú›Ô˘. ∏ ÌËÙ¤Ú· ˘Ô‚Ï‹ıËÎÂ ÛÂ ıÂÚ·Â›· ÌÂ ÁÔÓ·‰ÔÙÚÔ›ÓÂ˜ ÌÂ ·ÓÂÈÙ˘¯‹ ˆÚ›Ì·ÓÛË ˆÔı˘Ï·Î›ˆÓ, ÔfiÙÂ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ ˆ¿ÚÈÔ ‰fiÙÚÈ·˜ Ô˘ ÁÔÓÈÌÔÔÈ‹ıËÎÂ in vitro ÌÂ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÙÔ˘ ·Ù¤Ú·. ∏ ‰È·‰ÈÎ·Û›· ¤ÁÈÓÂ ÛÂ Î¤ÓÙÚÔ ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ ÙÔ˘ ÂÍˆÙÂÚÈÎÔ‡ (§ÔÓ‰›ÓÔ). √ ·Ù¤Ú·˜ Â›Ó·È ÁÓˆÛÙfi˜ ÊÔÚ¤·˜ ‰ÚÂ·ÓÔÎ˘ÙÙ·ÚÈÎ‹˜ ÓfiÛÔ˘, ÂÓÒ Ë ‰fiÙÚÈ· ˆ·Ú›Ô˘ ·Ó·Ê¤ÚÂÙÔ ˆ˜ Ê˘ÛÈÔÏÔÁÈÎ‹. ∆Ô ·È‰› ÛÂ ËÏÈÎ›· 6 ÌËÓÒÓ ÂÌÊ¿ÓÈÛÂ ÂÒ‰˘ÓË ‰ÈfiÁÎˆÛË ‰·ÎÙ‡ÏÔ˘ ‰ÂÍÈ¿˜ ¿ÎÚ·˜ ¯ÂÈÚfi˜. ™Â ËÏÈÎ›· 18 ÌËÓÒÓ ÂÌÊ¿ÓÈÛÂ ÂÒ‰˘ÓË ‰ÈfiÁÎˆÛË ‰ÂÍÈÔ‡ ·ÁÎÒÓ· Î·È ‰·ÎÙ‡ÏÔ˘ ‰ÂÍÈ¿˜ ¿ÎÚ·˜ ¯ÂÈÚfi˜ ÌÂ ÂÌ‡ÚÂÙÔ Î·È Ï›ÁÔ ·ÚÁfiÙÂÚ· ‰ÈfiÁÎˆÛË ‰·ÎÙ‡ÏÔ˘ ·ÚÈÛÙÂÚ‹˜ ¿ÎÚ·˜ ¯ÂÈÚfi˜. ∞Ú¯ÈÎ¿, ÏfiÁˆ ÙË˜ ÂÚÈÁÚ·Ê‹˜ ÙˆÓ ÂÂÈÛÔ‰›ˆÓ ˆ˜ ·ÏÒÓ ‰ÈÔÁÎÒÛÂˆÓ Î·È ÌÂ ‚¿ÛË ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ·ÏÏÂÚÁ›·˜, ıÂˆÚ‹ıËÎ·Ó ˆ˜ ·Ï‹ ÔÚÔÓÔÛ›· Î·È ¯ÔÚËÁ‹ıËÎ·Ó ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ‰‹ ÌÂ Î·Ï‹ ·ÓÙ·fiÎÚÈÛË. ∏ ÂÌÊ¿ÓÈÛË ›ÎÙÂÚÔ˘ Î·È ·Ó·ÈÌ›·˜ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ì›·˜ ÂÎ ÙˆÓ ÎÚ›ÛÂˆÓ, ÛÂ Û˘Ó‰˘·ÛÌfi ÌÂ ÙÔ ÈÛÙÔÚÈÎfi ÊÔÚÂ›·˜ ‰ÚÂ·ÓÔÎ˘ÙÙ·ÚÈÎ‹˜ ·Ó·ÈÌ›·˜ ÙÔ˘ ·Ù¤Ú·, ¤ıÂÛÂ ÛÙË ıÂÚ¿ÔÓÙ· È·ÙÚfi ÙËÓ ˘fiÓÔÈ· ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈ·˜, ÔfiÙÂ ÙÔ ·È‰› ·Ú·¤ÌÊıËÎÂ ÛÙÔ ·ÈÌ·ÙÔÏÔÁÈÎfi ÂÍˆÙÂÚÈÎfi È·ÙÚÂ›Ô. ∫ÏÈÓÈÎ¿ ·ÚÔ˘Û›·˙Â ‹·Ú ÌfiÏÈ˜ „ËÏ·ÊËÙfi Î·È ÛÏ‹Ó· ·„ËÏ¿ÊËÙÔ. √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ·È‰ÈÔ‡, ÙÔ˘ ·Ù¤Ú· Î·È ÙÔ˘ ‰›‰˘ÌÔ˘ ·‰ÂÏÊÔ‡ (¶›Ó·Î·˜ 2) ¤‰ÂÈÍÂ fiÙÈ ÙÔ ·È‰› Â›Ó·È ‰ÈÏfi˜ ÂÙÂÚÔ˙˘ÁÒÙË˜

‰ÚÂ·ÓÔÎ˘ÙÙ·ÚÈÎ‹˜ ÓfiÛÔ˘ Î·È ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈ·˜ D (D-Punjab). √È ÎÏÈÓÈÎ¤˜ ÂÎ‰ËÏÒÛÂÈ˜ ÙË˜ ‰ÈÏ‹˜ ·˘Ù‹˜ ÂÙÂÚÔ˙˘ÁˆÙ›·˜ Â›Ó·È fiÌÔÈÂ˜ ÌÂ ·˘Ù¤˜ ÙË˜ ‰ÚÂ·ÓÔÎ˘ÙÙ·ÚÈÎ‹˜ ÓfiÛÔ˘. ∆Ô ·È‰› ·Ú·ÎÔÏÔ˘ıÂ›Ù·È Û˘ÛÙËÌ·ÙÈÎ¿ ÛÙÔ ∞ÈÌ·ÙÔÏÔÁÈÎfi ∂ÍˆÙÂÚÈÎfi π·ÙÚÂ›Ô, ·ÚÔ˘ÛÈ¿˙ÂÈ ÂÚÈÛÙ·ÛÈ·Î¿ ÂÒ‰˘ÓÂ˜ ıÚÔÌ‚ˆÙÈÎ¤˜ ÎÚ›ÛÂÈ˜ ÔÈ ÔÔ›Â˜ ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È ÛÙÔ Û›ÙÈ ‹ ÙÔ ÓÔÛÔÎÔÌÂ›Ô, ÂÓÒ ‰È·ÙËÚÂ› Hb~7,8-8 gr/dl. 3Ô ÂÚÈÛÙ·ÙÈÎfi ∞ÁfiÚÈ ËÏÈÎ›·˜ 2,5 ÂÙÒÓ, ·ÔÙ¤ÏÂÛÌ· Î‡ËÛË˜ ÌÂÙ¿ ·fi ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË ÌÂ ¯Ú‹ÛË ‰fiÙË Û¤ÚÌ·ÙÔ˜. √ ·Ù¤Ú·˜ ÂÌÊ¿ÓÈ˙Â ÂÓ‰È¿ÌÂÛË ‚-ª∞ ÙË˜ ÔÔ›·˜ Ë ‰È¿ÁÓˆÛË ¤ÁÈÓÂ fiÙ·Ó ˘ËÚÂÙÔ‡ÛÂ ÙË ÛÙÚ·ÙÈˆÙÈÎ‹ ÙÔ˘ ıËÙÂ›·. ¢ÂÓ ¯ÚÂÈ¿ÛÙËÎÂ ÔÙ¤ ÌÂÙ¿ÁÁÈÛË, ‰È·ÙËÚÂ› Hb~9-10 gr/dl, ‰ÂÓ ¤¯ÂÈ Á›ÓÂÈ ÛÏËÓÂÎÙÔÌ‹, ÂÓÒ ¿Û¯ÂÈ ·fi ÈÓÛÔ˘ÏÈÓÔÂÍ·ÚÙÒÌÂÓÔ ‰È·‚‹ÙË ·fi 20ÂÙ›·˜. ∏ ÌËÙ¤Ú· Â›Ó·È ÁÓˆÛÙ‹ ÊÔÚ¤·˜ ‚-ª∞ Î·È ·ÚÔ˘Û›·˙Â ˘ÔÁÔÓÈÌfiÙËÙ· ÏfiÁˆ Û·ÏÈÁÁÈÎ‹˜ ·ÈÙÈÔÏÔÁ›·˜. ∞ÔÊ·Û›ÛÙËÎÂ Ó· ¯ÚËÛÈÌÔÔÈËıÂ› ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ‰fiÙË ÁÈ· Ó· ·ÔÊ‡ÁÔ˘Ó Èı·Ó‹ ÂÁÎ˘ÌÔÛ‡ÓË ·È‰ÈÔ‡ ÌÂ ‚-ª∞. ŒÁÈÓÂ ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË ÌÂ Û¤ÚÌ· ‰fiÙË ÌÂ ÂÈÙ˘¯‹ Î·Ù¿ÏËÍË. ∆Ô ·È‰› ÁÂÓÓ‹ıËÎÂ ÌÂ Î·ÈÛ·ÚÈÎ‹ ÙÔÌ‹ ÙËÓ 38Ë Â‚‰ÔÌ¿‰· (ÏfiÁˆ ÔÏ˘ÙÈÌfiÙËÙ·˜ ÙË˜ Î‡ËÛË˜). ™Â ËÏÈÎ›· 2 ¯ÚfiÓˆÓ ‰È·ÈÛÙÒıËÎÂ ·Ó·ÈÌ›· Î·È Ë·ÙÔÛÏËÓÔÌÂÁ·Ï›· ÌÂ ÈÎÙÂÚÈÎ‹ ¯ÚÔÈ¿ ‰¤ÚÌ·ÙÔ˜, ÔfiÙÂ ·Ú·¤ÌÊıËÎÂ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ¤ÏÂÁ¯Ô. ∞fi ÙËÓ ÎÏÈÓÈÎ‹ ÂÍ¤Ù·ÛË ‰È·ÈÛÙÒıËÎÂ ˆ¯ÚfiÙËÙ·, ÈÎÙÂÚÈÎ‹ ¯ÚÔÈ¿ ‰¤ÚÌ·ÙÔ˜, Û˘ÛÙÔÏÈÎfi Ê‡ÛËÌ· 2/6, ‹·Ú „ËÏ·ÊËÙfi 3 cm, ÛÏ‹Ó·˜ „ËÏ·ÊËÙfi˜ 6,5 cm.

¶›Ó·Î·˜ 2. ∂ÚÁ·ÛÙËÚÈ·Î¿ Â˘Ú‹Ì·Ù· ÔÈÎÔÁ¤ÓÂÈ·˜ 2Ô˘ ÂÚÈÛÙ·ÙÈÎÔ‡

Hb (g/dl) Ht (%) MCV (fl) MCH (pg) ªÔÚÊÔÏÔÁ›· ÂÚ˘ıÚÒÓ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜

ºÂÚÚÈÙ›ÓË (ng/ml) ∏b A Hb F HbD HbA2 HbS ∆ÂÛÙ ‰ÚÂ¿ÓˆÛË˜

¶¿Û¯ˆÓ

¶·Ù¤Ú·˜

∞‰ÂÏÊﬁ˜

8,5 25,7 84,3 27,9 ∞ÓÈÛÔÎ˘ÙÙ¿ÚˆÛË ++ ¶ÔÈÎÈÏÔÎ˘ÙÙ¿ÚˆÛË ++ ÀÔ¯ÚˆÌ›· ++ ∂Ú˘ıÚÔ‚Ï¿ÛÙÂ˜ ~10% ¢ÚÂ·ÓÔÎ‡ÙÙ·Ú· + 164,1 1,4% 21,4% 42,6%

14,4 41,8 89,3 30,8

12,8 35,8 72 24,3 ¶ÔÈÎÈÏÔÎ˘ÙÙ¿ÚˆÛË ± ÀÔ¯ÚˆÌ›· +

95,9 55,3% 0,7%

6,2 58,3% 1,7% 31,7% 1,8%

35,4% (+)

3,8% 33% (+)

(-) ¶·È‰È·ÙÚÈÎ‹ 2006;69:463-467

466

π. ∆Û¿ÙÚ· Î·È Û˘Ó.

√ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ (¶›Ó·Î·˜ 3) ¤‰ÂÈÍÂ ‰ÈÏ‹ ÂÙÂÚÔ˙˘ÁˆÙ›· ‚-ª∞ Î·È ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈ·˜ Lepore, Î·Ù¿ÛÙ·ÛË Ô˘ ÂÎÊÚ¿˙ÂÙ·È ÎÏÈÓÈÎ¿ fiÌÔÈ· ÌÂ ÔÌfi˙˘ÁÔ ‚-ª∞. ∆Ô ‚Ú¤ÊÔ˜ ‚Ú›ÛÎÂÙ·È ÛÂ ÚfiÁÚ·ÌÌ· Ù·ÎÙÈÎÒÓ ÌÂÙ·ÁÁ›ÛÂˆÓ.

™˘˙‹ÙËÛË ∏ ·ÏÌ·ÙÒ‰Ë˜ ÚfiÔ‰Ô˜ ÙË˜ ‚ÈÔÙÂ¯ÓÔÏÔÁ›·˜ ÛÙÔÓ ÙÔÌ¤· ÙË˜ ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ ‰›ÓÂÈ ÙÂÚ¿ÛÙÈÂ˜ ‰˘Ó·ÙfiÙËÙÂ˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙË˜ ˘ÔÁÔÓÈÌfiÙËÙ·˜, ·ÏÏ¿ Ù·˘Ùfi¯ÚÔÓ· ı¤ÙÂÈ Î·È ÔÏÏÔ‡˜ ÚÔ‚ÏËÌ·ÙÈÛÌÔ‡˜. ∏ ˘Ô‚ÔËıÔ‡ÌÂÓË ·Ó··Ú·ÁˆÁ‹, ÙfiÛÔ ÌÂ ÙË ÌÔÚÊ‹ ÙË˜ ÛÂÚÌ·Ù¤Á¯˘ÛË˜, fiÛÔ Î·È ÌÂ ÙË ÌÔÚÊ‹ ÙË˜ ÂÍˆÛˆÌ·ÙÈÎ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜, ‚ÔËı¿ÂÈ Ù· ¿ÙÂÎÓ· ˙Â˘Á¿ÚÈ· ÛÙËÓ ·fiÎÙËÛË ·È‰ÈÒÓ. √È ‰È¿ÊÔÚÂ˜ ÙÂ¯ÓÈÎ¤˜ ÂÍˆÛˆÌ·ÙÈÎ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ Â›Ó·È: Ë ÂÍˆÛˆÌ·ÙÈÎ‹ ÁÔÓÈÌÔÔ›ËÛË Î·È ÂÌ‚Ú˘ÔÌÂÙ·ÊÔÚ¿ (IVF/ET), Ë ÂÓ‰ÔÛ·ÏÈÁÁÈÎ‹ ÌÂÙ·ÊÔÚ¿ Á·ÌÂÙÒÓ (GIFT), Ë ÂÓ‰ÔÛ·ÏÈÁÁÈÎ‹ ÌÂÙ·ÊÔÚ¿ ˙˘ÁˆÙÒÓ (ZIFT) Î·È Ë ÂÓ‰ÔÎ˘ÙÙ·ÚÔÏ·ÛÌÈÎ‹/ ÂÓ‰Ôˆ·ÚÈÎ‹ ¤Á¯˘ÛË ÛÂÚÌ·ÙÔ˙ˆ·Ú›Ô˘ ‹ ·ÏÏÈÒ˜ “ÌÈÎÚÔÁÔÓÈÌÔÔ›ËÛË” (ICSI) (2,3,4). ÃÚËÛÈÌÔÔÈÔ‡ÓÙ·È Î˘Ú›ˆ˜ Ë IVF/ET Î·È Ë ICSI. ∏ ÙÂÏÂ˘Ù·›· ‰›ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ÁÔÓÈÌÔÔ›ËÛË˜ Î·È ·fiÎÙËÛË˜ ·È‰ÈÒÓ ·fi ˙Â˘Á¿ÚÈ· ÙˆÓ ÔÔ›ˆÓ ÔÈ ¿Ó‰ÚÂ˜ ¤¯Ô˘Ó ÛÔ‚·Úfi Úfi‚ÏËÌ· ÛÙÔÓ ·ÚÈıÌfi, ÙËÓ ÎÈÓËÙÈÎfiÙËÙ· ‹ ÙË ÌÔÚÊÔÏÔÁ›· ÙˆÓ ÛÂÚÌ·ÙÔ˙ˆ·Ú›ˆÓ ÂÍ·ÏÂ›ÊÔÓÙ·˜ ¤ÙÛÈ ÙËÓ ·Ó¿ÁÎË ¯Ú‹ÛË˜ ‰ˆÚËÙÒÓ Û¤ÚÌ·ÙÔ˜. ™ËÌ·ÓÙÈÎ‹ ÚfiÔ‰Ô˜ ¤¯ÂÈ Á›ÓÂÈ Î·È ÛÙÔÓ ÙÔÌ¤· ÙË˜ ÚÔÁÂÓÂÙÈÎ‹˜ ‰È¿ÁÓˆÛË˜. √ Î·ıÈÂÚˆÌ¤ÓÔ˜ ÚÔÁÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ·ÔÙÂÏÂ›Ù·È ·fi

ÙËÓ ·ÌÓÈÔÎ¤ÓÙËÛË, ÙË ‚ÈÔ„›· ¯ÔÚÈ·ÎÒÓ Ï·¯ÓÒÓ (CVS), ÙËÓ ·Ó¿Ï˘ÛË DNA ÙÚÔÊÔ‚Ï¿ÛÙË˜. ™Â ·Ú¯ÈÎ¿ ÛÙ¿‰È· ‚Ú›ÛÎÂÙ·È ÌÈ· Ó¤·, ÔÏÏ¿ ˘ÔÛ¯fiÌÂÓË Ì¤ıÔ‰Ô˜ Ë ÚÔÂÌÊ˘ÙÂ˘ÙÈÎ‹ ÁÂÓÂÙÈÎ‹ ‰È¿ÁÓˆÛË (PGD). ∏ PGD ‰È·Ê¤ÚÂÈ ·fi ÙÈ˜ Û˘Ó‹ıÂÈ˜ ÌÂıfi‰Ô˘˜, Î·ıÒ˜ ÚÔÛÊ¤ÚÂÈ ÛÙ· ˙Â˘Á¿ÚÈ· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ·ÔÊ‡ÁÔ˘Ó ÌÈ· Î‡ËÛË ¿Û¯ÔÓÙÔ˜ ÂÌ‚Ú‡Ô˘, Î·ıÒ˜ ÂÈÙÚ¤ÂÈ ÙËÓ ÂÈÏÔÁ‹ ÌË ·Û¯fiÓÙˆÓ ÂÌ‚Ú‡ˆÓ ÁÈ· ÂÌ‚Ú˘ÔÌÂÙ·ÊÔÚ¿. ∏ Ì¤ıÔ‰Ô˜ ·˘Ù‹ ÁÈ· ÙË ¯ÒÚ· Ì·˜ ¤¯ÂÈ ÙÂÚ¿ÛÙÈ· ÛËÌ·Û›·, Î·ıÒ˜ ÌÔÚÂ› Ó· ‰È·ÁÓÒÛÂÈ Ù· ¿Û¯ÔÓÙ· ·fi ÌÂÛÔÁÂÈ·Î¿ Û‡Ó‰ÚÔÌ· ¤Ì‚Ú˘· Î·È Ó· Ù· ·ÔÎÏÂ›ÛÂÈ ·fi ÙËÓ ÂÌÊ‡ÙÂ˘ÛË (5,6). øÛÙfiÛÔ, Ë ÙÂ¯ÓËÙ‹ ÁÔÓÈÌÔÔ›ËÛË, ˆ˜ Ú·Á‰·›· ·Ó·Ù˘ÛÛfiÌÂÓÔ˜ Ó¤Ô˜ ÙÔÌ¤·˜, ‰ÂÓ ¤¯ÂÈ ·ÎfiÌ· Ï·ÈÛÈˆıÂ› ·fi ÙÔ ··Ú·›ÙËÙÔ ÓÔÌÈÎfi Ï·›ÛÈÔ. ∫¤ÓÙÚ· ÁÔÓÈÌÔÔ›ËÛË˜ È‰Ú‡ÔÓÙ·È Î·È ÙÔ ÛËÌ·ÓÙÈÎfiÙÂÚÔ, ÏÂÈÙÔ˘ÚÁÔ‡Ó ¯ˆÚ›˜ ıÂÛÌÔıÂÙËÌ¤ÓÔ˘˜ Î·È ÔÌÔÈÔÁÂÓÂ›˜ Î·ÓfiÓÂ˜ ÏÂÈÙÔ˘ÚÁ›·˜, Ô˘ Ó· ¤¯Ô˘Ó ÚÔ¤ÏıÂÈ ·fi ÙËÓ ·Ó·ÁÓˆÚÈÛÌ¤ÓË ¤ÁÎÚÈÙË È·ÙÚÈÎ‹ ÎÔÈÓfiÙËÙ·. ™ÙËÓ ∂ÏÏ¿‰· Û‹ÌÂÚ· ÏÂÈÙÔ˘ÚÁÔ‡Ó ÂÚ› Ù· 54 Î¤ÓÙÚ·, Î·Ù·ÓÂÌËÌ¤Ó· ÛÂ ‰È¿ÊÔÚÂ˜ fiÏÂÈ˜, Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ÔÔ›ˆÓ ·ÔÙÂÏÔ‡Ó È‰ÈˆÙÈÎ¤˜ ÚˆÙÔ‚Ô˘Ï›Â˜. Ã·Ú·ÎÙËÚÈÛÙÈÎ¿, ÛÙÔ ÚÒÙÔ ÂÚÈÛÙ·ÙÈÎfi Ô˘ ·Ó·Ê¤ÚıËÎÂ, ¤ÁÈÓÂ ÚÔÛ¿ıÂÈ· Â·Ê‹˜ ÌÂ ÙÔ Î¤ÓÙÚÔ fiÔ˘ ¤ÁÈÓÂ Ë ÙÂ¯ÓËÙ‹ ÁÔÓÈÌÔÔ›ËÛË. ∞ÔÙ¤ÏÂÛÌ· ‰ÂÓ ˘‹ÚÍÂ, Î·ıÒ˜ ÙÔ Î¤ÓÙÚÔ ¤ÎÏÂÈÛÂ ÌÂÙ¿ ·fi Ï›ÁÔ˘˜ Ì‹ÓÂ˜ ÏÂÈÙÔ˘ÚÁ›·˜, ¯ˆÚ›˜ Ó· ‰È·ÙËÚËıÂ› Î¿ÔÈÔ ·Ú¯Â›Ô. ∏ ‰ÈÂ‡ı˘ÓÛË ÙÔ˘ Î¤ÓÙÚÔ˘ ·Ó·ÊÂÚfiÙ·Ó fiÙÈ ·ÔÙÂÏÂ›ÙÔ ·fi ·ÏÏÔ‰·Ô‡˜. ™·Ó ·ÔÙ¤ÏÂÛÌ·, ÛÙÔ ıÔÏfi ÙÔ›Ô Ô˘ ¤¯ÂÈ ‰ËÌÈÔ˘ÚÁËıÂ›, ÔÏÏ¤˜ ÊÔÚ¤˜ ÂÌÊ·Ó›˙ÔÓÙ·È ÂÛÊ·ÏÌ¤ÓÂ˜ Ú·ÎÙÈÎ¤˜, Ô˘ Ô‰ËÁÔ‡Ó ÛÂ ·Ù˘¯‹

¶›Ó·Î·˜ 3. ∂ÚÁ·ÛÙËÚÈ·Î¿ Â˘Ú‹Ì·Ù· ÔÈÎÔÁ¤ÓÂÈ·˜ 3Ô˘ ÂÚÈÛÙ·ÙÈÎÔ‡

Hb (g/dl) Ht (%) MCV (fl) MCH (pg) ªÔÚÊÔÏÔÁ›· ÂÚ˘ıÚÒÓ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ¢∂∫ (%) HbA ∏b A2 ∏b Lepore Hb F ¶·È‰È·ÙÚÈÎ‹ 2006;69:463-467

¶¿Û¯ˆÓ

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7,2 23 58,4 18,3 ∞ÓÈÛÔÎ˘ÙÙ¿ÚˆÛË +++ ¶ÔÈÎÈÏÔÎ˘ÙÙ¿ÚˆÛË +++ ™ÙÔ¯ÔÎ˘ÙÙ¿ÚˆÛË + ÀÔ¯ÚˆÌ›· +++ µ·ÛÂﬁÊÈÏÔ˜ ÛÙ›ÍË + 2,5% 14% 2% 12% 70,6%

12,2 38,2 70,3 22,4 ÀÔ¯ÚˆÌ›· + ∞ÓÈÛÔÎ˘ÙÙ¿ÚˆÛË + ¶ÔÈÎÈÏÔÎ˘ÙÙ¿ÚˆÛË +

5,1% (-) <2%

∞ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜ ÌÂÙ¿ ·ﬁ ˘Ô‚ÔËıÔ‡ÌÂÓË ÁÔÓÈÌÔÔ›ËÛË

·ÔÙÂÏ¤ÛÌ·Ù· fiˆ˜ ·˘Ù¿ ÙˆÓ ·Ó·ÊÂÚfiÌÂÓˆÓ ·È‰ÈÒÓ. ∂›Ó·È ÂÈÙ·ÎÙÈÎ‹ ·Ó¿ÁÎË ÁÈ· ·˘ÛÙËÚfiÙÂÚÔ ¤ÏÂÁ¯Ô ÛÂ fiÏÂ˜ ÙÈ˜ ‰È·‰ÈÎ·Û›Â˜ ÙˆÓ Î¤ÓÙÚˆÓ, ÂÈ‰ÈÎ¿ ÛÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ‰ˆÚËÙÒÓ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡. ÕÏÏˆÛÙÂ Î·È Ù· ÙÚ›· ÂÚÈÛÙ·ÙÈÎ¿ Ô˘ ÂÚÈÁÚ¿ÊËÎ·Ó, ı· Â›¯·Ó ¿ÏÏË Î·Ù¿ÏËÍË ·Ó Â›¯Â Á›ÓÂÈ ÏËÚ¤ÛÙÂÚÔ˜ ¤ÏÂÁ¯Ô˜ ÛÙÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ. ∂È‰ÈÎ¿ ÛÙÔ ÙÚ›ÙÔ ÂÚÈÛÙ·ÙÈÎfi ÔÈ ÁÔÓÂ›˜ Â¤ÏÂÍ·Ó Û˘ÓÂÈ‰ËÙ¿ ÙË ¯Ú‹ÛË Í¤ÓÔ˘ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡, ÁÈ· Ó· ·ÔÊ‡ÁÔ˘Ó Èı·Ó‹ Á¤ÓÓËÛË ·È‰ÈÔ‡ ÌÂ ÛÔ‚·Ú‹ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈ·. ™Â ÔÏÏ¤˜ ¯ÒÚÂ˜ ÙÔ˘ ÂÍˆÙÂÚÈÎÔ‡ Á›ÓÔÓÙ·È ÚÔÛ¿ıÂÈÂ˜ Ó· ıÂÛÌÔıÂÙËıÔ‡Ó Û˘ÁÎÂÎÚÈÌ¤ÓÔÈ Î·ÓfiÓÂ˜ ÏÂÈÙÔ˘ÚÁ›·˜ ÁÈ· Ù· Î¤ÓÙÚ· ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜, ÒÛÙÂ Ó· ·ÔÊÂ‡ÁÔÓÙ·È Ï¿ıË fiˆ˜ Ù· ·Ú·¿Óˆ. ™ÙÈ˜ ∏¶∞, ÚˆÙÔfiÚÔ ¯ÒÚ· ÛÙËÓ ÂÊ·ÚÌÔÁ‹ ÙˆÓ Ó¤ˆÓ ÙÂ¯ÓÈÎÒÓ, Á›ÓÂÙ·È ÂÂÍÂÚÁ·Û›· Î·È ¤Î‰ÔÛË Î·ÓfiÓˆÓ ÁÈ· ÙËÓ ÔÚı‹ Î·È ÂÓÈ·›· ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ Î¤ÓÙÚˆÓ ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ ·fi ÙËÓ American Society for Reproductive Medicine (7). ™ÙËÓ ∂˘Úˆ·˚Î‹ ŒÓˆÛË ‰ÂÓ ˘¿Ú¯ÂÈ ÂÓÈ·›· ÓÔÌÔıÂÛ›· Î·È ÔÈ Ú·ÎÙÈÎ¤˜ ÔÈÎ›ÏÔ˘Ó ·fi ¯ÒÚ· ÛÂ ¯ÒÚ·. øÛÙfiÛÔ ¤¯Ô˘Ó Á›ÓÂÈ ÚÔÛ¿ıÂÈÂ˜ ·Ó¿ÏÔÁÂ˜ ÌÂ ÙÈ˜ ∏¶∞, ÌÂ ÙËÓ ˘ÔÛÙ‹ÚÈÍË Î·È ÙËÓ ¯ÚËÌ·ÙÔ‰fiÙËÛË ÙË˜ ∂˘Úˆ·˚Î‹˜ ∂ÈÙÚÔ‹˜, fiˆ˜ ÙÔ Û‡ÌÊˆÓÔ ÙÔ˘ Corsendonk (8). ™ÙËÓ ∂ÏÏ¿‰· ˆÛÙfiÛÔ ¤¯Ô˘ÌÂ ÌÂÁ¿ÏÔ ÎÂÓfi ÓÔÌÔıÂÛ›·˜. ∆Ô 1992 „ËÊ›ÛÙËÎÂ ÓfiÌÔ˜ (v. 2071/92 ¿ÚıÚÔ 59 [º∂∫ 123/15-7-92]) Ô˘ ÚÔ‚Ï¤ÂÈ ÙË Û‡ÛÙ·ÛË Î·È ÏÂÈÙÔ˘ÚÁ›· ÌÔÓ¿‰ˆÓ ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜, Î·ıÒ˜ Â›ÛË˜ Î·È ÙËÓ ¤Î‰ÔÛË ¶ÚÔÂ‰ÚÈÎÔ‡ ¢È·Ù¿ÁÌ·ÙÔ˜ ÌÂ ÙÔ ÔÔ›Ô Î·ıÔÚ›˙ÔÓÙ·Ó “ÔÈ fiÚÔÈ Î·È ÔÈ ÚÔ¸Ôı¤ÛÂÈ˜ Û˘ÛÙ¿ÛÂˆ˜ Î·È ÏÂÈÙÔ˘ÚÁ›·˜ ÌÔÓ¿‰ˆÓ ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ ÙÔ˘ ·ÓıÚÒÔ˘ Î·È Î¿ıÂ ÏÂÙÔÌ¤ÚÂÈ· Û¯ÂÙÈÎ¿ ÌÂ ÙËÓ ËıÈÎ‹, ‰ÂÔÓÙÔÏÔÁÈÎ‹, ÓÔÌÈÎ‹ Î·È ÔÈÎÔÓÔÌÈÎ‹ Ú‡ıÌÈÛË ÙÔ˘ fiÏÔ˘ ı¤Ì·ÙÔ˜”, ÙÔ ÔÔ›Ô ‰ÂÓ ¤¯ÂÈ ÂÎ‰ÔıÂ› ·ÎfiÌË. ∆Ô 2002 ÂÎ‰fiıËÎÂ ÓÔÌÔÛ¯¤‰ÈÔ (v. 3089/2002 [º∂∫ ∞ 327/2312-2002] ÁÈ· ÙËÓ È·ÙÚÈÎ¿ ˘Ô‚ÔËıÔ‡ÌÂÓË ·Ó··Ú·ÁˆÁ‹), Ô˘ Û˘ÌÏËÚÒÓÂÈ ÛÙÔÈ¯Â›· ÙÔ˘ ·ÛÙÈÎÔ‡ ÎÒ‰ÈÎ·, ¯ˆÚ›˜ fiÌˆ˜ Ó· ·Ó·Ê¤ÚÂÙ·È ÛÙ· Î¤ÓÙÚ· ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜. ∞fi ÏËÚÔÊÔÚ›Â˜ ÙÔ˘ ¤ÓÙ˘Ô˘ Î·È ËÏÂÎÙÚÔÓÈÎÔ‡ Ù‡Ô˘ Ê·›ÓÂÙ·È fiÙÈ Â›ÎÂÈÙ·È „‹ÊÈÛË Û¯Â‰›Ô˘ ÓfiÌÔ˘ Ô˘ ı· Ú˘ıÌ›˙ÂÈ fiÏÂ˜ ÙÈ˜ ÏÂÈÙÔ˘ÚÁ›Â˜ Î·È Ù· ÎÂÓ¿ ÙˆÓ ÚÔËÁËı¤ÓÙˆÓ ÓfiÌˆÓ Î·È ˘Ô˘ÚÁÈÎÒÓ ·ÔÊ¿-

467

ÛÂˆÓ. ™˘ÌÂÚ·ÛÌ·ÙÈÎ¿ ÛÂ ÌÈ· ¯ÒÚ· Û·Ó ÙËÓ ∂ÏÏ¿‰·, fiÔ˘ ÙÔ 7,5% ÙÔ˘ ÏËı˘ÛÌÔ‡ ÙË˜ Â›Ó·È ÊÔÚÂ›˜ ‚-ª∞ Î·È fiÔ˘ ÌÂÙ¿ ·fi ÌÂÁ¿ÏË ÚÔÛ¿ıÂÈ· ÙË˜ ¶·ÁÎfiÛÌÈ·˜ √ÚÁ¿ÓˆÛË˜ ÀÁÂ›·˜ ÌÂ ÚÔÁÚ¿ÌÌ·Ù· ÚfiÏË„Ë˜ ÙË˜ ÓfiÛÔ˘ ÂÈÙÂ‡¯ıËÎ·Ó ÙfiÛ· ÔÏÏ¿, Â›Ó·È ËıÈÎ¿ Î·È ÂÈÛÙËÌÔÓÈÎ¿ ··Ú¿‰ÂÎÙÔ Ó· Á›ÓÔÓÙ·È ·ÚfiÌÔÈ· ÛÊ¿ÏÌ·Ù·. ∆Ô ÎÂÓfi Ô˘ ˘Ê›ÛÙ·Ù·È ·fi ÙÔÓ ÌË Î·ıÔÚÈÛÌfi Ì¤¯ÚÈ Û‹ÌÂÚ· Â·ÎÚÈ‚ÒÓ fiÚˆÓ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ ÌÔÓ¿‰ˆÓ ÙÂ¯ÓËÙ‹˜ ÁÔÓÈÌÔÔ›ËÛË˜ ÚÔÎ·ÏÂ› ÎÈÓ‰‡ÓÔ˘˜ ÁÈ· ÙË ‰ËÌfiÛÈ· ˘ÁÂ›·. ∏ ¤ÏÏÂÈ„Ë Ô˘ÛÈ·ÛÙÈÎ‹˜ ÔÚÁ¿ÓˆÛË˜ ÙˆÓ ÂÌÏÂÎfiÌÂÓˆÓ ÊÔÚ¤ˆÓ Î·È Î·Ù¿ Û˘Ó¤ÂÈ· Ë ·‰˘Ó·Ì›· ¿ÛÎËÛË˜ ·ÔÙÂÏÂÛÌ·ÙÈÎÔ‡ ÂÏ¤Á¯Ô˘, ·Ó·Ì¤ÓÂÙ·È Ó· ·˘Í‹ÛÂÈ ÙË Á¤ÓÓËÛË ·È‰ÈÒÓ ÌÂ ·ÈÌÔÛÊ·ÈÚÈÓÔ¿ıÂÈÂ˜. ¶Ú¤ÂÈ ÂÔÌ¤Óˆ˜ Û‡ÓÙÔÌ·, Ó· Á›ÓÔ˘Ó ÔÈ ··Ú·›ÙËÙÂ˜ ÓÔÌÔıÂÙÈÎ¤˜ Ú˘ıÌ›ÛÂÈ˜ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÂÈÛÙËÌÔÓÈÎÒÓ, ‰ÂÔÓÙÔÏÔÁÈÎÒÓ, ËıÈÎÒÓ, ÎÔÈÓˆÓÈÎÒÓ Î·È ÔÈÎÔÓÔÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ÙÔ˘ fiÏÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Kattamis C, Mallias A, Metaxotou-Mavromati A, Matsaniotis N. Screening for beta-thalassaemias. Lancet. 1981;2(8252):930. 2. Wen SW, Walker M., Léveillé MC, Leader A. Intracytoplasmic sperm injection: promises and challenges. CMAJ 2004;171(8):845-846. 3. Toner J. Progress we can be proud of: U.S. trends in assisted reproduction over the first 20 years. Fertil Steril 2002;78:943-950. 4. Van Voorhis BJ, Sparks AE, Allen BD, Stovall DW, Syrop CH, Chapler FK. Cost-effectiveness of infertility treatments: a cohort study. Fertil Steril 1997;67: 830-836. 5. Traeger-Synodinos J, Vrettou C, Palmer G, Tzetis M, Mastrominas M, Davies S et al. An evaluation of PGD in clinical genetic services through 3 years application for prevention of beta-thalassaemia major and sickle cell thalassaemia. Mol Hum Reprod. 2003;9:301-307. 6. Kanavakis E, Traeger-Synodinos J. Preimplantation genetic diagnosis in clinical practice. J Med Genet. 2002;39:6-11. 7. The American Society for Reproductive Medicine. 2002 guidelines for gamete and embryo donation: a practice committee report: guidelines and minimum standards. Fertil Steril 2002;77 (Suppl 5):1. 8. Barratt C, Englert Y, Gottlieb C, Jouannet P. Gamete donation guidelines. The Corsendonk consensus document for the European Union. Hum Reprod. 1998;13:500-501.

¶·È‰È·ÙÚÈÎ‹ 2006;69:463-467

468

¶ƒ∞∫∆π∫√ £∂ª∞

PRACTICAL ISSUE

√‰ËÁ›Â˜ ÁÈ· ¿ÛÎËÛË ÛÂ ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ ÌÂ Û˘ÁÁÂÓÂ›˜ ‹ Â›ÎÙËÙÂ˜ ·ı‹ÛÂÈ˜ ÙÔ˘ Î˘ÎÏÔÊÔÚÈÎÔ‡ ∫·Ú‰ÈÔÏÔÁÈÎﬁ ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ∞ıËÓÒÓ, “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” AÏÏËÏÔÁÚ·Ê›·: ¢ËÌ‹ÙÚË˜ °ÂˆÚÁ·ÎﬁÔ˘ÏÔ˜ ∏ÚÈ‰·ÓÔ‡ 16, ∆.∫. 115 28, ∞ı‹Ó· E-mail: geodim4@hotmail.com ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 20-03-2006 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛË˜: 10-10-2006

¢. °ÂˆÚÁ·ÎﬁÔ˘ÏÔ˜, °. ¶··‰ﬁÔ˘ÏÔ˜

¶ÂÚ›ÏË„Ë: ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· fiÏÔ Î·È ÂÚÈÛÛfiÙÂÚ· ·È‰È¿ Î·È ¤ÊË‚ÔÈ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ ÔÚÁ·ÓˆÌ¤ÓÂ˜ ·ıÏËÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜. ∆· ÔÊ¤ÏË ·fi ÙËÓ ÂÓ·Û¯fiÏËÛË ·˘Ù‹ Â›Ó·È ÔÏÏ¿ Î·È ÚÔÊ·Ó‹, ÙfiÛÔ ÛÂ ÛˆÌ·ÙÈÎfi fiÛÔ Î·È ÛÂ „˘¯ÈÎfi Â›Â‰Ô. ¶·Ú¿ÏÏËÏ· ¤¯ÂÈ ·˘ÍËıÂ› Î·È Ô ·ÚÈıÌfi˜ ÙˆÓ ·È‰ÈÒÓ ÌÂ Î·Ú‰ÈÔ¿ıÂÈ· Ù· ÔÔ›· ÂÈ‚ÈÒÓÔ˘Ó Î·È Ù· ÔÔ›· Êı¿ÓÔ˘Ó ÛÙËÓ ÂÊË‚ÈÎ‹ ‹ ÚÔÂÊË‚ÈÎ‹ ËÏÈÎ›· ÛÂ Î·Ï‹ Î·Ù¿ÛÙ·ÛË Î·È Ù· ÔÔ›·, fiˆ˜ Â›Ó·È Â˘ÓfiËÙÔ, ÂÈı˘ÌÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó Î·È ·˘Ù¿ Ì·˙› ÌÂ ÙÔ˘˜ Û˘ÓÔÌËÏ›ÎÔ˘˜ ÙÔ˘˜ ÛÂ ·ıÏËÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜. ¢˘ÛÙ˘¯Ò˜ fiÌˆ˜, ÔÈ ÁÔÓÂ›˜ ·ÏÏ¿ Î·È ÌÂÁ¿ÏÔ Ì¤ÚÔ˜ ÙË˜ È·ÙÚÈÎ‹˜ ÎÔÈÓfiÙËÙ·˜ Â›Ó·È ‰ÈÛÙ·ÎÙÈÎÔ› ‹ ·ÎfiÌ· Î·È ÙÂÏÂ›ˆ˜ ·ÚÓËÙÈÎÔ› ÛÙÔ Ó· ÂÈÙÚ¤„Ô˘Ó ÙËÓ ÂÓ·Û¯fiÏËÛË ÌÂ ÙÔÓ ·ıÏËÙÈÛÌfi ÛÙ· ·È‰È¿ ·˘Ù¿, ÊÔ‚Ô‡ÌÂÓÔÈ ÙÈ˜ Èı·Ó¤˜ ‰˘Û¿ÚÂÛÙÂ˜ Û˘Ó¤ÂÈÂ˜. Ÿˆ˜ Ê·›ÓÂÙ·È, fiÌˆ˜, ·fi ÙË Û¯ÂÙÈÎ‹ ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›·, Ë ¿ıÏËÛË ˘fi ÔÚÈÛÌ¤ÓÂ˜ ÚÔ¸Ôı¤ÛÂÈ˜ Â›Ó·È ·ÛÊ·Ï‹˜ ÁÈ· ÙË Û˘ÓÙÚÈÙÈÎ‹ ÏÂÈÔ„ËÊ›· ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ, ·ÎfiÌ· Î·È ÌÂ ÙË ÌÔÚÊ‹ ÙË˜ ·ÓÙ·ÁˆÓÈÛÙÈÎ‹˜ Û˘ÌÌÂÙÔ¯‹˜ Î·È ÙÔ˘ ÚˆÙ·ıÏËÙÈÛÌÔ‡. ŸÌˆ˜, ·ÎfiÌ· Î·È fiÙ·Ó ‰ÂÓ ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ÓÙ·ÁˆÓÈÛÙÈÎ¿ ·ıÏ‹Ì·Ù·, Â›Ó·È ÂÊÈÎÙ‹ Î·È ÂÈÙÚÂÙ‹ Ë ÂÓ·Û¯fiÏËÛË ÌÂ Î¿ÔÈÂ˜ ·ıÏËÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜ ÛÂ ¯·Ï·Ú‹, „˘¯·ÁˆÁÈÎ‹ ÌÔÚÊ‹. ∆Ô ¿ÚıÚÔ ·˘Ùfi ÂÈ¯ÂÈÚÂ› Ó· Û˘Ì˘ÎÓÒÛÂÈ Î·È Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ ÛÂ Ú·ÎÙÈÎ‹ ÌÔÚÊ‹ Ù· Û¯ÂÙÈÎ¿ Û˘ÌÂÚ¿ÛÌ·Ù· Î·È Ô‰ËÁ›Â˜ ‰ÈÂıÓÒÓ ÂÈÙÚÔÒÓ Ô˘ ·ÊÔÚÔ‡Ó ÛÙËÓ ¿ıÏËÛË ·È‰ÈÒÓ ÌÂ ÙÈ˜ Û˘¯ÓfiÙÂÚÂ˜ Û˘ÁÁÂÓÂ›˜ ‹ Â›ÎÙËÙÂ˜ ·ı‹ÛÂÈ˜ ÙÔ˘ Î˘ÎÏÔÊÔÚÈÎÔ‡. §¤ÍÂÈ˜ ÎÏÂÈ‰È¿: ÕÛÎËÛË, Î·Ú‰ÈÔ¿ıÂÈÂ˜.

Exercise recommendations for children and adolescents with congenital and acquired cardiovascular disorders Cardiology Department, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece Correspondence: Dimitris Georgakopoulos 16, Iridanou St., 115 28 Athens, Greece E-mail: geodim4@hotmail.com Date of submission: 20-03-2006 Date of approval: 10-10-2006

D. Georgakopoulos, G. Papadopoulos

Abstract: During the last decade the numbers of children and adolescents participating in organized athletic activities have increased. The benefits from this participation are multiple and obvious. Over the same time, the number of children with cardiovascular abnormalities who survive and reach adolescence in relatively good condition is also increasing. These children, as it is to be expected, are keen to participate in sports activities along with their healthy peers. Unfortunately, most of the parents taking care of these children and the physicians responsible for their monitoring are reluctant to allow them to exercise, let alone compete with other children. This reluctance is not supported by the relevant bibliography, which demonstrates that for the vast majority of these children some form of exercise is allowable, following careful, thorough and regular evaluation of their condition. Some of these children and adolescents can even participate in competitive sports, but even when this is not possible, certain forms of recreational sports activity may be well tolerated, without risk for the children. This review summarizes and presents in a practical way the present state of knowledge and the recommendations of international committees regarding the participation in sports of children and adolescents with cardiovascular abnormalities. Key words: Exercise, cardiovascular disease.

∂ÈÛ·ÁˆÁ‹ ∆· ÙÂÏÂ˘Ù·›· ¯ÚﬁÓÈ·, ÏﬁÁˆ ÙˆÓ ÛËÌ·ÓÙÈÎÒÓ ÂÍÂÏ›ÍÂˆÓ ÛÙÔÓ ÙÔÌ¤· ÙË˜ ¯ÂÈÚÔ˘ÚÁÈÎ‹˜ Î·È ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

ÂÂÌ‚·ÙÈÎ‹˜ ·ÓÙÈÌÂÙÒÈÛË˜ ÙˆÓ Û˘ÁÁÂÓÒÓ Î·Ú‰ÈÔ·ıÂÈÒÓ, ¤Ó·˜ ‰È·ÚÎÒ˜ ·˘Í·ÓﬁÌÂÓÔ˜ ·ÚÈıÌﬁ˜ ·ÛıÂÓÒÓ Êı¿ÓÂÈ ÛÙËÓ ÂÊË‚Â›· Î·È ÛÙËÓ ÂÓ‹ÏÈÎË ˙ˆ‹ ÛÂ ÈÎ·ÓÔÔÈËÙÈÎ‹ ¤ˆ˜ ÔÏ‡ Î·Ï‹

469

ÕÛÎËÛË Î·È ·ı‹ÛÂÈ˜ ÙÔ˘ Î˘ÎÏÔÊÔÚÈÎÔ‡

Ê˘ÛÈÎ‹ Î·Ù¿ÛÙ·ÛË Î·È ÌÂ fiÏÂ˜ ÙÈ˜ ÚÔ¸Ôı¤ÛÂÈ˜ ÁÈ· Ó· ÌÔÚÂ› Ó· ˙‹ÛÂÈ ÌÈ· fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ÈÔ Ê˘ÛÈÔÏÔÁÈÎ‹ ˙ˆ‹. Ÿˆ˜ Â›Ó·È ·Ó·ÌÂÓfiÌÂÓÔ, ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ·fi ÙÔ˘˜ ·ÛıÂÓÂ›˜ ·˘ÙÔ‡˜ ÂÈı˘ÌÔ‡Ó Ó· ·ÎÔÏÔ˘ı‹ÛÔ˘Ó ÙÈ˜ Û‡Á¯ÚÔÓÂ˜ Ù¿ÛÂÈ˜ Î·È Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÂÓÂÚÁ¿ ÛÂ ·ıÏËÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜, ÁÂÁÔÓfi˜ Ô˘ ı· ÙÔ˘˜ ÚÔÛÊ¤ÚÂÈ ÛËÌ·ÓÙÈÎ¿ ÔÊ¤ÏË ÙfiÛÔ ÛÙË ÛˆÌ·ÙÈÎ‹ fiÛÔ Î·È ÛÙËÓ „˘¯ÈÎ‹ ÙÔ˘˜ ˘ÁÂ›·. ∏ ÁÂÓÈÎfiÙÂÚË fiÌˆ˜ ·ÓÙ›ÏË„Ë, ÙfiÛÔ ÙˆÓ ÁÔÓ¤ˆÓ ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ fiÛÔ Î·È Ì¤ÚÔ˘˜ ÙÔ˘ È·ÙÚÈÎÔ‡ ÎfiÛÌÔ˘, Â›Ó·È fiÙÈ ÏfiÁˆ ÙË˜ ˘¿Ú¯Ô˘Û·˜ Î·Ú‰ÈÔ¿ıÂÈ·˜, ‰ÈÔÚıˆıÂ›Û·˜ ‹ ÌË, ÔÈ ·ÛıÂÓÂ›˜ ·˘ÙÔ› ‰ÂÓ ÂÈÙÚ¤ÂÙ·È Ó· ·ıÏÔ‡ÓÙ·È ÌÂ ÙÔÓ Êfi‚Ô ÙÔ˘ ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ ‹ ÙË˜ ÂÈ‰Â›ÓˆÛË˜ ÙË˜ Î·Ù¿ÛÙ·Û‹˜ ÙÔ˘˜. ∏ ·ÓÙ›ÏË„Ë ·˘Ù‹ ÂÓÈÛ¯‡ÂÙ·È Î·È ·fi ÙË ÌÂÁ¿ÏË ‰ËÌÔÛÈfiÙËÙ· Ô˘ Ï·Ì‚¿ÓÔ˘Ó Ù· Û¿ÓÈ· ÂÚÈÛÙ·ÙÈÎ¿ ·ÈÊÓ›‰ÈˆÓ ı·Ó¿ÙˆÓ Ô˘ Û˘Ì‚·›ÓÔ˘Ó Î·Ù¿ ÙËÓ ¿ÛÎËÛË ÓÂ·ÚÒÓ ·ıÏËÙÒÓ (1). Ÿˆ˜ fiÌˆ˜ Ê·›ÓÂÙ·È ·fi ÙË Û¯ÂÙÈÎ‹ ‚È‚ÏÈÔÁÚ·Ê›·, Ë Û˘ÓÙÚÈÙÈÎ‹ ÏÂÈÔ„ËÊ›· ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ ÌÔÚÔ‡Ó Ó· Ï·Ì‚¿ÓÔ˘Ó Ì¤ÚÔ˜ ÛÂ Î¿ÔÈ· ·ıÏËÙÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ·, ¯ˆÚ›˜ Êfi‚Ô ÁÈ· ÙËÓ ˘ÁÂ›· ÙÔ˘˜, ÌÂ ÙËÓ ÚÔ¸fiıÂÛË, ‚Â‚·›ˆ˜, fiÙÈ ı· ÚÔËÁÂ›Ù·È Î¿ıÂ ÊÔÚ¿ Ô ÂÓ‰Â‰ÂÈÁÌ¤ÓÔ˜ ¤ÏÂÁ¯Ô˜ Î·È ı· Û˘ÓÈÛÙ¿Ù·È Ë Î·Ù¿ÏÏËÏË ÁÈ· Î¿ıÂ ·ÛıÂÓ‹ ‰Ú·ÛÙËÚÈfiÙËÙ· (2). ™ÎÔfi˜ ÏÔÈfiÓ ÙÔ˘ ·ÚfiÓÙÔ˜ ¿ÚıÚÔ˘ Â›Ó·È Ó· Û˘ÁÎÂÓÙÚÒÛÂÈ Î·È Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ ÂÚÈÏËÙÈÎ¿ Î·È ÌÂ Û·Ê‹ÓÂÈ· ÙÈ˜ ˘¿Ú¯Ô˘ÛÂ˜ Ô‰ËÁ›Â˜ ÁÈ· ¿ÛÎËÛË Ô˘ ·ÊÔÚÔ‡Ó ÙÈ˜ Û˘¯ÓfiÙÂÚÂ˜ ·ı‹ÛÂÈ˜ ÙÔ˘ Î˘ÎÏÔÊÔÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, Û˘ÁÁÂÓÂ›˜ ‹ ÌË, ÔÈ ÔÔ›Â˜ ··ÓÙÒÓÙ·È ÛÂ ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜.

∂›‰Ë ¿ÛÎËÛË˜ - ∆·ÍÈÓfiÌËÛË ·ıÏËÌ¿ÙˆÓ ∏ ¿ÛÎËÛË ‰È·ÎÚ›ÓÂÙ·È ÛÂ ‰‡Ô ‚·ÛÈÎÔ‡˜ Ù‡Ô˘˜, ÙË ‰˘Ó·ÌÈÎ‹ Î·È ÙË ÛÙ·ÙÈÎ‹ (3,4). ™ÙË ‰˘Ó·ÌÈÎ‹ ¿ÛÎËÛË Á›ÓÔÓÙ·È Ú˘ıÌÈÎ¤˜ Û˘Û¿ÛÂÈ˜ ÙˆÓ ÂÌÏÂÎfiÌÂÓˆÓ Ì˘˚ÎÒÓ ÔÌ¿‰ˆÓ ÌÂ ÌÂÙ·‚ÔÏ¤˜ ÛÙÔ Ì‹ÎÔ˜ ÙË˜ Ì˘˚Î‹˜ ›Ó·˜ Î·È ÌÂ ·Ó¿Ù˘ÍË ÌÈÎÚ‹˜ ÂÓ‰ÔÌ˘˚Î‹˜ Ù¿ÛË˜. ∞ÓÙ›ıÂÙ·, ÛÙË ÛÙ·ÙÈÎ‹ ¿ÛÎËÛË ·Ú·ÙËÚÂ›Ù·È ÌÂÁ¿ÏË ·‡ÍËÛË ÙË˜ ÂÓ‰ÔÌ˘˚Î‹˜ Ù¿ÛË˜ ÌÂ ÔÏ‡ ÌÈÎÚ‹ ÌÂÙ·‚ÔÏ‹ ÛÙÔ Ì‹ÎÔ˜ ÙË˜ Ì˘˚Î‹˜ ›Ó·˜. Ÿˆ˜ Â›Ó·È ·Ó·ÌÂÓfiÌÂÓÔ, ÔÈ ÂÈÙÒÛÂÈ˜ ÛÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ· Â›Ó·È ‰È·ÊÔÚÂÙÈÎ¤˜ ÛÂ Î¿ıÂ Ù‡Ô ¿ÛÎËÛË˜. ∏ ‰˘Ó·ÌÈÎ‹ ¿ÛÎËÛË ÚÔÎ·ÏÂ› ÛËÌ·ÓÙÈÎ‹ ·‡ÍËÛË ÙË˜ Î·Ú‰È·Î‹˜ Û˘¯ÓfiÙËÙ·˜, ÙÔ˘ fiÁÎÔ˘ ·ÏÌÔ‡, ÙË˜ Î·Ú‰È·Î‹˜ ·ÚÔ¯‹˜ Î·È ÙË˜ Û˘ÛÙÔÏÈÎ‹˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜ Î·È ÙÒÛË ÙˆÓ ÔÏÈÎÒÓ ÂÚÈÊÂÚÈÎÒÓ

·ÓÙÈÛÙ¿ÛÂˆÓ Î·È ÙË˜ ‰È·ÛÙÔÏÈÎ‹˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜. ∞ÔÙ¤ÏÂÛÌ· fiÏˆÓ ·˘ÙÒÓ ÙˆÓ ÌÂÙ·‚ÔÏÒÓ Â›Ó·È Ë ÚfiÎÏËÛË ÛÙËÓ Î·Ú‰È¿ ˘ÂÚÊfiÚÙˆÛË˜ fiÁÎÔ˘. ∏ ÛÙ·ÙÈÎ‹ ¿ÛÎËÛË ÚÔÎ·ÏÂ› ÛËÌ·ÓÙÈÎ‹ ·‡ÍËÛË ÙfiÛÔ ÙË˜ Û˘ÛÙÔÏÈÎ‹˜ fiÛÔ Î·È ÙË˜ ‰È·ÛÙÔÏÈÎ‹˜ ·ÚÙËÚÈ·Î‹˜ ›ÂÛË˜, ÌÂ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ˘ÂÚÊfiÚÙˆÛË ›ÂÛË˜ ÙÔ˘ Î˘ÎÏÔÊÔÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜. ¡· ÛËÌÂÈˆıÂ› fiÙÈ Î·Ù¿ ÙË ‰˘Ó·ÌÈÎ‹ ¿ÛÎËÛË ÌÂÁ¿ÏˆÓ Ì˘˚ÎÒÓ ÔÌ¿‰ˆÓ ÛÂ ˘„ËÏ¿ Â›Â‰· ·ÓÙ›ÛÙ·ÛË˜ (.¯. ·ÁˆÓÈÛÙÈÎ‹ Ô‰ËÏ·Û›·), ÔÈ ÂÈÙÒÛÂÈ˜ ÛÙÔ Î˘ÎÏÔÊÔÚÈÎfi Â›Ó·È ·ÚfiÌÔÈÂ˜ ÌÂ ·˘Ù¤˜ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙË˜ ¿ÛÎËÛË˜ ÛÙ·ÙÈÎÔ‡ Ù‡Ô˘ (5). Ÿˆ˜ Â›Ó·È Î·Ù·ÓÔËÙfi, ÔÏÏ¿ ·ıÏ‹Ì·Ù· ÂÚÈ¤¯Ô˘Ó Û˘ÓÈÛÙÒÛÂ˜ Î·È ÙˆÓ ‰‡Ô Ù‡ˆÓ ¿ÛÎËÛË˜, ÛÂ ‰È·ÊÔÚÂÙÈÎ‹ ‚Â‚·›ˆ˜ ·Ó·ÏÔÁ›· ÙÔ Î·ı¤Ó· (6). °È· ÏfiÁÔ˘˜ Ù·ÍÈÓfiÌËÛË˜ ‰È·ÎÚ›ÓÔ˘ÌÂ ÙÚ›· Â›Â‰· ¤ÓÙ·ÛË˜ (¯·ÌËÏfi, Ì¤ÙÚÈÔ Î·È ˘„ËÏfi) ÁÈ· Î¿ıÂ ¤Ó·Ó ·fi ÙÔ˘˜ Ù‡Ô˘˜ ¿ÛÎËÛË˜ (‰˘Ó·ÌÈÎ‹ ‹ ÛÙ·ÙÈÎ‹) Î·È ¤ÙÛÈ Î¿ıÂ ¿ıÏËÌ· ÙÔÔıÂÙÂ›Ù·È ÛÙËÓ ·Ó¿ÏÔÁË ı¤ÛË ÛÙÔÓ Û¯ÂÙÈÎfi ›Ó·Î· (¶›Ó·Î·˜ 1). ¶·Ú·‰Â›ÁÌ·ÙÔ˜ ¯¿ÚÈÓ, ÙÔ bowling Ù·ÍÈÓÔÌÂ›Ù·È ÛÙËÓ Î·ÙËÁÔÚ›· π∞, Ô˘ ÛËÌ·›ÓÂÈ fiÙÈ Î·Ù¿ ÙËÓ ÂÎÙ¤ÏÂÛ‹ ÙÔ˘ ··ÈÙÂ›Ù·È ¿ÛÎËÛË ¯·ÌËÏ‹˜ ¤ÓÙ·ÛË˜ ÙfiÛÔ ÛÂ ‰˘Ó·ÌÈÎfi fiÛÔ Î·È ÛÂ ÛÙ·ÙÈÎfi ÛÙÔÈ¯Â›Ô. ∞ÓÙ›ıÂÙ·, Ë ÎˆËÏ·Û›· ÙÔÔıÂÙÂ›Ù·È ÛÙËÓ Î·ÙËÁÔÚ›· πππ°, Ô˘ Û˘ÓÂ¿ÁÂÙ·È ˘„ËÏ‹˜ ¤ÓÙ·ÛË˜ ‰˘Ó·ÌÈÎ‹ Î·È ÛÙ·ÙÈÎ‹ ÚÔÛ¿ıÂÈ·. ∞Ó Î·È ‰ÂÓ ·Ó·Ê¤ÚÂÙ·È ÛÙÔÓ Û¯ÂÙÈÎfi ›Ó·Î·, ı· ÌÔÚÔ‡ÛÂ Ó· ÚÔÛÙÂıÂ› Î·È ÙÔ Ì·Ï¤ÙÔ, ÌÈ· ¿ÛÎËÛË ‹È·˜ ÌÔÚÊ‹˜, È‰È·›ÙÂÚ· ÚÔÛÊÈÏ‹˜ ÛÙ· ÎÔÚ›ÙÛÈ·. ∂›ÛË˜ ÌÈ· ¿ÏÏË Î·ÙËÁÔÚ›· Ô˘ ÂÓ‰È·Ê¤ÚÂÈ ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ Û˘ÁÁÂÓÂ›˜ Î·Ú‰ÈÔ¿ıÂÈÂ˜ Â›Ó·È Ù· ·ıÏ‹Ì·Ù· ÂÎÂ›Ó· Ù· ÔÔ›· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍËÌ¤ÓÔ Î›Ó‰˘ÓÔ ÛˆÌ·ÙÈÎ‹˜ ÚfiÛÎÚÔ˘ÛË˜, Ë ÔÔ›· ‚Â‚·›ˆ˜ ÂÁÎ˘ÌÔÓÂ› ÛÔ‚·ÚÔ‡˜ ÎÈÓ‰‡ÓÔ˘˜ ÁÈ· ÔÚÈÛÌ¤ÓÔ˘˜ ·fi ·˘ÙÔ‡˜ (¶›Ó·Î·˜ 2). ™˘ÁÁÂÓÂ›˜ Î·Ú‰ÈÔ¿ıÂÈÂ˜ (7) ªÂÛÔÎÔÏÈÎ‹ ÂÈÎÔÈÓˆÓ›·: ŸÙ·Ó Ë ÂÈÎÔÈÓˆÓ›· Â›Ó·È ÌÈÎÚÔ‡ ÌÂÁ¤ıÔ˘˜ (·Ô˘Û›· ‰È¿Ù·ÛË˜ ÙË˜ ‰ÂÍÈ¿˜ ÎÔÈÏ›·˜), Ë Û˘ÌÌÂÙÔ¯‹ Â›Ó·È ÂÏÂ‡ıÂÚË ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·. ŸÙ·Ó Ë ÂÈÎÔÈÓˆÓ›· Â›Ó·È ·ÈÌÔ‰˘Ó·ÌÈÎ¿ ÛËÌ·ÓÙÈÎ‹, ÌÂ ‰È¿Ù·ÛË ÙË˜ ‰ÂÍÈ¿˜ ÎÔÈÏ›·˜ Î·È Ê˘ÛÈÔÏÔÁÈÎ‹, fiÌˆ˜, ›ÂÛË ÛÙËÓ ÓÂ˘ÌÔÓÈÎ‹ ·ÚÙËÚ›·, ÙfiÙÂ ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·. ŸÙ·Ó ˘¿Ú¯ÂÈ Ì¤ÙÚÈ· ÓÂ˘ÌÔÓÈÎ‹ ˘¤ÚÙ·ÛË, ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ıÏ‹Ì·Ù· Î·ÙËÁÔÚ›·˜ π∞. ŸÙ·Ó Ë ÓÂ˘ÌÔÓÈÎ‹ ˘¤ÚÙ·ÛË Â›Ó·È ÛÔ‚·Ú‹, ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

470

¢. °ÂˆÚÁ·ÎﬁÔ˘ÏÔ˜, °. ¶··‰ﬁÔ˘ÏÔ˜

¶›Ó·Î·˜ 1. ∆·ÍÈÓﬁÌËÛË ·ıÏËÌ¿ÙˆÓ ∞

- ÌﬁÔ˘ÏÈÓÁÎ - ÁÎÔÏÊ - ÛÎÔÔ‚ÔÏ‹

- ÂÈÙÚ·¤˙È· ·ÓÙÈÛÊ·›ÚÈÛË - Ù¤ÓÈ˜ (‰ÈÏﬁ) - ‚ﬁÏÂ˚

- Ô‰fiÛÊ·ÈÚÔ - Ù¤ÓÈ˜ - ÛÎÔ˘fi˜ - ‰ÚfiÌÔÈ ÌÂÁ¿ÏˆÓ ·ÔÛÙ¿ÛÂˆÓ

ππ

- ÙÔÍÔ‚ÔÏ›· - È·Û›·* - Î·Ù·‰‡ÛÂÈ˜* - ·ÁÒÓÂ˜ ·˘ÙÔÎÈÓ‹ÙˆÓ Î·È ÌÔÙÔÛÈÎÏÂÙÒÓ*

- ÍÈÊ·ÛÎ›· - ÛÙ›‚Ô˜ (¿ÏÌ·Ù·) - ÙÚ¤ÍÈÌÔ ÛÚÈÓÙ - Î·ÏÏÈÙÂ¯ÓÈÎﬁ ·ÙÈÓ¿˙ - Û˘Á¯ÚÔÓÈÛÌ¤ÓË ÎÔÏ‡Ì‚ËÛË* - Û¤ÚÊÈÓÁÎ

- Ì¿ÛÎÂÙ - ¯ﬁÎÂ˚ Â› ¿ÁÔ˘ - ÎÔÏ‡Ì‚ËÛË - ¯¿ÓÙÌÔÏ

πππ

- ÛÙ›‚Ô˜ (Ú›„ÂÈ˜) - Á˘ÌÓ·ÛÙÈÎ‹* - Î·Ú¿ÙÂ - ÈÛÙÈÔÏÔ˝· - ·Ó·ÚÚ›¯ËÛË* - ı·Ï¿ÛÛÈÔ ÛÎÈ* - ¿ÚÛË ‚·ÚÒÓ* - ÈÛÙÈÔÛ·Ó›‰·*

- ¿ÏË - ÛÎÈ ‚Ô˘ÓÔ‡*

- ˘ÁÌ·¯›· - Î·Óﬁ Î·ÁÈ¿Î - Ô‰ËÏ·Û›·* - ‰¤Î·ıÏÔ - ÎˆËÏ·Û›· - ·ÁÔ‰ÚÔÌ›Â˜

π = ¯·ÌËÏ‹ ÛÙ·ÙÈÎ‹, ππ = Ì¤ÙÚÈ· ÛÙ·ÙÈÎ‹, πππ = ˘„ËÏ‹ ÛÙ·ÙÈÎ‹, ∞ = ¯·ÌËÏ‹ ‰˘Ó·ÌÈÎ‹, µ = Ì¤ÙÚÈ· ‰˘Ó·ÌÈÎ‹, ° = ˘„ËÏ‹ ‰˘Ó·ÌÈÎ‹, * = ·˘ÍËÌ¤ÓÔ˜ Î›Ó‰˘ÓÔ˜ Û˘ÁÎÔ‹˜

ÌÂ ÂÎ‰‹ÏˆÛË Î˘·ÓÒÛÂˆ˜, ÙfiÙÂ ··ÁÔÚÂ‡ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ÓÙ·ÁˆÓÈÛÙÈÎ¿ ·ıÏ‹Ì·Ù·. ªÂÛÔÎÔÈÏÈ·Î‹ ÂÈÎÔÈÓˆÓ›·: ÕÙÔÌ· ÌÂ ÌÈÎÚ¤˜ ‹ Ì¤ÙÚÈÂ˜ ÂÈÎÔÈÓˆÓ›Â˜ (Qp/Qs = 1,5-1,9) ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÂÏÂ‡ıÂÚ· ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·. ŸÙ·Ó Ë ÂÈÎÔÈÓˆÓ›· Â›Ó·È ÌÂÁ¿ÏË (Qp/Qs >2) ÙfiÙÂ ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ıÏ‹Ì·Ù· Î·ÙËÁÔÚ›·˜ π∞. ∫·È ÛÙÈ˜ ‰‡Ô ·˘Ù¤˜ ·ı‹ÛÂÈ˜, 6 Ì‹ÓÂ˜ ÌÂÙ¿ ÙË ‰ÈfiÚıˆÛË Â›ÙÂ ·˘Ù‹ Á›ÓÂÈ ÂÂÌ‚·ÙÈÎ¿, Â›ÙÂ ¯ÂÈÚÔ˘ÚÁÈÎ¿, ÂÈÙÚ¤Â¶›Ó·Î·˜ 2. ∞ıÏ‹Ì·Ù· ÌÂ Î›Ó‰˘ÓÔ ÛˆÌ·ÙÈÎ‹˜ ÚfiÛÎÚÔ˘ÛË˜ 1. ¶Ô‰fiÛÊ·ÈÚÔ 2. π·Û›· 3. ∫·Ù·‰‡ÛÂÈ˜ 4. ∞ÁÒÓÂ˜ ·˘ÙÔÎÈÓ‹ÙˆÓ 5. ∞ÁÒÓÂ˜ ÌÔÙÔÛÈÎÏÂÙÒÓ 6. ∫·ÏÏÈÙÂ¯ÓÈÎfi ·ÙÈÓ¿˙ 7. ™˘Á¯ÚÔÓÈÛÌ¤ÓË ÎÔÏ‡Ì‚ËÛË 8. ™¤ÚÊÈÓÁÎ 9. ª¿ÛÎÂÙ 10. ÃfiÎÂ˚ Â› ¿ÁÔ˘ 11. °˘ÌÓ·ÛÙÈÎ‹ 12. ∫·Ú¿ÙÂ 13. ∞Ó·ÚÚ›¯ËÛË 14. £·Ï¿ÛÛÈÔ ÛÎÈ 15. ÕÚÛË ‚·ÚÒÓ 16. πÛÙÈÔÛ·Ó›‰· 17. ™ÎÈ ‚Ô˘ÓÔ‡ 18. ¶¿ÏË 19. ¶˘ÁÌ·¯›· 20. ¶Ô‰ËÏ·Û›· ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

Ù·È ÂÏÂ‡ıÂÚ· Ë ¿ıÏËÛË ÂÊfiÛÔÓ ÔÈ ·ÛıÂÓÂ›˜ Â›Ó·È ·Û˘ÌÙˆÌ·ÙÈÎÔ› Î·È ‰ÂÓ ÂÌÊ·Ó›˙Ô˘Ó ·ÚÚ˘ıÌ›·, Ì˘ÔÎ·Ú‰È·Î‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Î·È ÂÓ‰Â›ÍÂÈ˜ ÓÂ˘ÌÔÓÈÎ‹˜ ˘¤ÚÙ·ÛË˜. ∞ÓÔÈÎÙfi˜ ‚ÔÙ¿ÏÂÈÔ˜ fiÚÔ˜: ∂› ÌÈÎÚÔ‡ fiÚÔ˘ Ë ¿ıÏËÛË Â›Ó·È ÂÏÂ‡ıÂÚË. ŸÙ·Ó Ô fiÚÔ˜ Â›Ó·È ·ÈÌÔ‰˘Ó·ÌÈÎ¿ ÛËÌ·ÓÙÈÎfi˜ (‰È¿Ù·ÛË ÙË˜ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜), ÂÈÙÚ¤ÂÙ·È ÌfiÓÔ Ë Î·ÙËÁÔÚ›· π∞. ∆ÚÂÈ˜ Ì‹ÓÂ˜ ÌÂÙ¿ ÙËÓ ÂÂÌ‚·ÙÈÎ‹ Û‡ÁÎÏÂÈÛË Î·È ¤ÍÈ Ì‹ÓÂ˜ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈÎ‹, ÂÈÙÚ¤ÔÓÙ·È fiÏ· Ù· ·ıÏ‹Ì·Ù· ÂÊfiÛÔÓ ÈÛ¯‡Ô˘Ó ÔÈ ÚÔ¸Ôı¤ÛÂÈ˜ Ô˘ ·Ó·Ê¤ÚıËÎ·Ó Î·È ÁÈ· ÙÈ˜ ¿ÏÏÂ˜ ‰‡Ô ÂÈÎÔÈÓˆÓ›Â˜. ™Ù¤ÓˆÛË ÓÂ˘ÌÔÓÈÎ‹˜ ‚·Ï‚›‰·˜: ŸÙ·Ó Ë ÎÏ›ÛË ›ÂÛË˜ (Doppler Ì¤ÙÚËÛË) Â›Ó·È <40 mmHg Î·È Ë ÏÂÈÙÔ˘ÚÁ›· ÙË˜ ‰ÂÍÈ¿˜ ÎÔÈÏ›·˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ‹, ÂÈÙÚ¤ÔÓÙ·È fiÏ· Ù· ·ıÏ‹Ì·Ù·. ŸÙ·Ó Ë ÎÏ›ÛË ›ÂÛË˜ ˘ÂÚ‚Â› Ù· 40 mmHg, ÂÈÙÚ¤ÂÙ·È ÌfiÓÔ Ë Î·ÙËÁÔÚ›· π∞ Î·È πµ, Î·È Ô ·ÛıÂÓ‹˜ Û˘Ó‹ıˆ˜ ·Ú·¤ÌÂÙ·È ÁÈ· ‚·Ï‚È‰ÔÏ·ÛÙÈÎ‹. ŒÓ· Ì‹Ó· ÌÂÙ¿ ÙË ‚·Ï‚È‰ÔÏ·ÛÙÈÎ‹ ÌÂ Ì·ÏfiÓÈ Î·È ÙÚÂÈ˜ Ì‹ÓÂ˜ ÌÂÙ¿ ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô Ë ¿ıÏËÛË Â›Ó·È ÂÏÂ‡ıÂÚË, ÂÊfiÛÔÓ ‰ÂÓ ˘¿Ú¯Ô˘Ó Û˘ÌÙÒÌ·Ù· Î·È Ë ÏÂÈÙÔ˘ÚÁ›· ÙË˜ ÎÔÈÏ›·˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ‹. ™Ù¤ÓˆÛË ·ÔÚÙÈÎ‹˜ ‚·Ï‚›‰·˜: ∞ÛıÂÓÂ›˜ ÌÂ ‹È· ÛÙ¤ÓˆÛË (Doppler ÎÏ›ÛË ›ÂÛË˜ <20 mmHg) Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·, ·Ó ‰ÂÓ ·Ó·Ê¤ÚÔ˘Ó Û˘ÌÙÒÌ·Ù· Û¯ÂÙÈ˙fiÌÂÓ· ÌÂ ÙËÓ ¿ıÏËÛË Î·È Ù· ∏∫° ËÚÂÌ›·˜ Î·È ÎfiˆÛË˜

471

ÕÛÎËÛË Î·È ·ı‹ÛÂÈ˜ ÙÔ˘ Î˘ÎÏÔÊÔÚÈÎÔ‡

Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ¿. ŸÙ·Ó Ë ÛÙ¤ÓˆÛË Â›Ó·È Ì¤ÙÚÈ· (ÎÏ›ÛË ›ÂÛË˜ 21-49 mmHg) ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ıÏ‹Ì·Ù· ÙˆÓ Î·ÙËÁÔÚÈÒÓ π∞, πµ Î·È ππ∞ ÂÊfiÛÔÓ ‰ÂÓ ˘¿Ú¯Ô˘Ó Û˘ÌÙÒÌ·Ù·, ‰ÂÓ ˘¿Ú¯ÂÈ strain ÛÙÔ ∏∫° ËÚÂÌ›·˜, ÛÙÔ Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ· ˘¿Ú¯ÂÈ ÌfiÓÔ ‹È· ˘ÂÚÙÚÔÊ›· ÙË˜ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜ Î·È Ë ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ‹. ∞ÛıÂÓÂ›˜ ÌÂ ÛÔ‚·Ú‹ ÛÙ¤ÓˆÛË (ÎÏ›ÛË ›ÂÛË˜ >50 mmHg) ‰ÂÓ ÂÈÙÚ¤ÂÙ·È Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ ·ÓÙ·ÁˆÓÈÛÙÈÎ¿ ·ıÏ‹Ì·Ù·. ∆ÚÂÈ˜ Ì‹ÓÂ˜ ÌÂÙ¿ ÙË ‚·Ï‚È‰ÔÏ·ÛÙÈÎ‹ ‹ ÙË ¯ÂÈÚÔ˘ÚÁÈÎ‹ ‰È¿ÓÔÈÍË ÂÈÙÚ¤ÂÙ·È Ë ÂÓ·Û¯fiÏËÛË ÌÂ ÙÔÓ ·ıÏËÙÈÛÌfi, ·Ó¿ÏÔÁ· ÌÂ ÙÔÓ ‚·ıÌfi ÙË˜ ˘ÔÏÂÈfiÌÂÓË˜ ÛÙ¤ÓˆÛË˜ ‹ ·ÓÂ¿ÚÎÂÈ·˜. ∞ÓÂ¿ÚÎÂÈ· ·ÔÚÙ‹˜ (8): ™˘Ó‹ıˆ˜ ÛÙ· ·È‰È¿ Â›Ó·È ·fiÙÔÎÔ˜ ‰›Ù˘¯Ë˜ ·ÔÚÙÈÎ‹˜ ‚·Ï‚›‰·˜ ‹ ‚·Ï‚È‰ÔÏ·ÛÙÈÎ‹˜ ÌÂ Ì·ÏfiÓÈ. Ã·Ú·ÎÙËÚ›˙ÂÙ·È ‹È· fiÙ·Ó ‰ÂÓ ˘¿Ú¯Ô˘Ó ÂÚÈÊÂÚÈÎ¿ ÛËÌÂ›· ·ÔÚÙÈÎ‹˜ ·ÓÂ¿ÚÎÂÈ·˜ Î·È ÙÔ Ì¤ÁÂıÔ˜ ÙË˜ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎfi, Ì¤ÙÚÈ· fiÙ·Ó ˘¿Ú¯Ô˘Ó ÂÚÈÊÂÚÈÎ¿ ÛËÌÂ›· Î·È Ë ·ÚÈÛÙÂÚ‹ ÎÔÈÏ›· ·ÚÔ˘ÛÈ¿˙ÂÈ ‹È· ‰È¿Ù·ÛË ÌÂ Ê˘ÛÈÔÏÔÁÈÎ‹, fiÌˆ˜, Û˘ÛÙÔÏÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· Î·È ÛÔ‚·Ú‹ fiÙ·Ó ˘¿Ú¯ÂÈ ÌÂÁ¿ÏË ‰È¿Ù·ÛË ÙË˜ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜ ‹/Î·È ˘ÔÛ˘ÛÙ·ÏÙÈÎfiÙËÙ· ·˘Ù‹˜. ŸÏÔÈ ÔÈ ·ÛıÂÓÂ›˜ ÌÂ ·ÔÚÙÈÎ‹ ·ÓÂ¿ÚÎÂÈ· ¯ÚÂÈ¿˙ÔÓÙ·È ÂÎÙ›ÌËÛË ÙÔ˘Ï¿¯ÈÛÙÔÓ Ì›· ÊÔÚ¿ ÙÔÓ ¯ÚfiÓÔ ÌÂ Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ·, ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È ÂÓ‰Â¯ÔÌ¤Óˆ˜ Î·È Ì·ÁÓËÙÈÎ‹ ÙÔÌÔÁÚ·Ê›·, Ë ÔÔ›· ÂÈÙÚ¤ÂÈ Î·Ï‡ÙÂÚË ÂÎÙ›ÌËÛË ÙÔ˘ ‚·ıÌÔ‡ ÙË˜ ·ÓÂ¿ÚÎÂÈ·˜ Î·È ÙË˜ Èı·Ó‹˜ ‰È¿Ù·ÛË˜ ÙË˜ ·ÔÚÙÈÎ‹˜ Ú›˙·˜ Ô˘ Û˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ. ŸÙ·Ó Ë ·ÓÂ¿ÚÎÂÈ· Â›Ó·È ‹È· ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ fiÏÂ˜ ÙÈ˜ Î·ÙËÁÔÚ›Â˜, ÂÓÒ fiÙ·Ó Â›Ó·È Ì¤ÙÚÈ· ÛÙÈ˜ Î·ÙËÁÔÚ›Â˜ π Î·È ππ, ÌÂ ÙËÓ ÚÔ¸fiıÂÛË, ‚Â‚·›ˆ˜, fiÙÈ ÔÈ ·ÛıÂÓÂ›˜ Â›Ó·È ·Û˘ÌÙˆÌ·ÙÈÎÔ›. ∞Ó ˘¿Ú¯ÂÈ ÎÔÈÏÈ·Î‹ ·ÚÚ˘ıÌ›· ÛÙËÓ ËÚÂÌ›· ‹ ÛÙËÓ ¿ÛÎËÛË, ÙfiÙÂ ÂÈÙÚ¤ÂÙ·È ÌfiÓÔ Ë Î·ÙËÁÔÚ›· π∞. ∂› ÛÔ‚·Ú‹˜ ·ÓÂ¿ÚÎÂÈ·˜ ··ÁÔÚÂ‡ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ fiÏ· Ù· ·ÓÙ·ÁˆÓÈÛÙÈÎ¿ ·ıÏ‹Ì·Ù·. ŸÙ·Ó Ë ·ÓÂ¿ÚÎÂÈ· ÔÊÂ›ÏÂÙ·È ÛÂ ‰›Ù˘¯Ë ·ÔÚÙÈÎ‹ ‚·Ï‚›‰·, Ô˘ Â›Ó·È Î·È ÙÔ Ï¤ÔÓ Û‡ÓËıÂ˜, ı· Ú¤ÂÈ Ó· ÏËÊıÂ› ˘’ fi„ÈÓ Î·È ÙÔ Ì¤ÁÂıÔ˜ ÙË˜ ·ÔÚÙÈÎ‹˜ Ú›˙·˜. ŸÙ·Ó Ë ·ÔÚÙÈÎ‹ Ú›˙· Â›Ó·È <40 mm ÂÈÙÚ¤ÔÓÙ·È fiÏ· Ù· ·ıÏ‹Ì·Ù·, ÂÓÒ fiÙ·Ó Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ·fi 45 mm ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÌfiÓÔ ÛÂ Î·ÙËÁÔÚ›· π∞. πÛıÌÈÎ‹ ÛÙ¤ÓˆÛË ·ÔÚÙ‹˜: ∞ÛıÂÓÂ›˜ ÌÂ ‹È· ÛÙ¤ÓˆÛË (ÎÏ›ÛË ›ÂÛË˜ < 20 mmHg), Ê˘ÛÈÔÏÔÁÈÎ‹ ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È Ì¤ÁÈÛÙË Û˘ÛÙÔÏÈÎ‹ ·ÚÙËÚÈ·Î‹ ›ÂÛË ÛÙËÓ ÎfiˆÛË <230

mmHg, ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·. ™Â ·ÓÙ›ıÂÙË ÂÚ›ÙˆÛË, Î·È Ì¤¯ÚÈ Ó· ·ÓÙÈÌÂÙˆÈÛıÂ› Ë ÓfiÛÔ˜, Û˘ÌÌÂÙ¤¯Ô˘Ó ÌfiÓÔ ÛÙËÓ Î·ÙËÁÔÚ›· π∞. ŒÍÈ Ì‹ÓÂ˜ ÌÂÙ¿ ÙË ‰ÈfiÚıˆÛË (¯ÂÈÚÔ˘ÚÁÈÎ‹ ‹ ·ÁÁÂÈÔÏ·ÛÙÈÎ‹) ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙ· ÂÚÈÛÛfiÙÂÚ· ·ıÏ‹Ì·Ù· (ÂÍ·ÈÚÔ‡ÓÙ·È ·˘Ù¿ ÙË˜ Î·ÙËÁÔÚ›·˜ πππ Î·È Ù· ·ıÏ‹Ì·Ù· ÌÂ Î›Ó‰˘ÓÔ ÛˆÌ·ÙÈÎ‹˜ ÚfiÛÎÚÔ˘ÛË˜), ÂÊfiÛÔÓ Ë ÎÏ›ÛË ›ÂÛË˜ Â›Ó·È <20 mmHg Î·È Ë Û˘ÛÙÔÏÈÎ‹ ·ÚÙËÚÈ·Î‹ ›ÂÛË Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ‹ ÙfiÛÔ ÛÙËÓ ËÚÂÌ›· fiÛÔ Î·È ÛÙËÓ ÎfiˆÛË. ªÂÙ¿ ÙË Û˘ÌÏ‹ÚˆÛË ÂÓfi˜ ¤ÙÔ˘˜ ÂÈÙÚ¤ÔÓÙ·È fiÏÂ˜ ÔÈ Î·ÙËÁÔÚ›Â˜ ·ıÏËÌ¿ÙˆÓ ÌÂ ÌfiÓË ÂÍ·›ÚÂÛË ÙËÓ ¿ÚÛË ‚·ÚÒÓ. ŸÙ·Ó ˘¿Ú¯ÂÈ ·ÓÂ‡Ú˘ÛÌ· ‹ ÛËÌ·ÓÙÈÎ‹ ‰È¿Ù·ÛË ÙË˜ ·ÔÚÙ‹˜, ÂÈÙÚ¤ÂÙ·È ÌfiÓÔ Ë Î·ÙËÁÔÚ›· π∞. ∆ÂÙÚ·ÏÔÁ›· Fallot: ∆Ë ÛËÌÂÚÈÓ‹ ÂÔ¯‹ Û¯Â‰fiÓ fiÏÔÈ ÔÈ ·ÛıÂÓÂ›˜ ÌÂ ÙÂÙÚ·ÏÔÁ›· ¤¯Ô˘Ó ˘Ô‚ÏËıÂ› ÛÂ ¯ÂÈÚÔ˘ÚÁÈÎ‹ ‰ÈfiÚıˆÛË ÓˆÚ›˜ Î·Ù¿ ÙËÓ ÚÒÙË ·È‰ÈÎ‹ ËÏÈÎ›· Î·È ÛÙËÓ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ù· ·ÔÙÂÏ¤ÛÌ·Ù· Â›Ó·È ÈÎ·ÓÔÔÈËÙÈÎ¿. ŒÙÛÈ, ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ fiÏÂ˜ ÙÈ˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜ ÂÊfiÛÔÓ ÏËÚÔ‡ÓÙ·È ÔÈ ·Ú·Î¿Ùˆ ÚÔ¸Ôı¤ÛÂÈ˜: ·) Ê˘ÛÈÔÏÔÁÈÎfi Ì¤ÁÂıÔ˜ ‰ÂÍÈ¿˜ ÎÔÈÏ›·˜ ÌÂ Ê˘ÛÈÔÏÔÁÈÎ‹ ‹ Û¯Â‰fiÓ Ê˘ÛÈÔÏÔÁÈÎ‹ ›ÂÛË, ‚) ·Ô˘Û›· ÛËÌ·ÓÙÈÎ‹˜ ·Ú·Ì¤ÓÔ˘Û·˜ ÌÂÛÔÎÔÈÏÈ·Î‹˜ ÂÈÎÔÈÓˆÓ›·˜ Î·È Á) ·Ô˘Û›· ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ Ú˘ıÌÔ‡ ÛÙË ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È ÙËÓ 24ˆÚË Î·Ù·ÁÚ·Ê‹ ÙÔ˘ Ú˘ıÌÔ‡. ∞ÓÙ›ıÂÙ·, fiÙ·Ó ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈÎ‹ ·ÓÂ¿ÚÎÂÈ· ÓÂ˘ÌÔÓÈÎ‹˜ ‚·Ï‚›‰·˜, ›ÂÛË ‰ÂÍÈ¿˜ ÎÔÈÏ›·˜ >50% ÙË˜ Û˘ÛÙËÌ·ÙÈÎ‹˜ ‹ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Ú˘ıÌÔ‡, ÙfiÙÂ ÂÈÙÚ¤ÂÙ·È ÌfiÓÔ Ë Î·ÙËÁÔÚ›· π∞, ÂÂÈ‰‹ Ô Î›Ó‰˘ÓÔ˜ ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ Â›Ó·È ·˘ÍËÌ¤ÓÔ˜ (9). ªÂÙ¿ıÂÛË ÙˆÓ ÌÂÁ¿ÏˆÓ ·ÁÁÂ›ˆÓ: ™ÙÔ˘˜ ·ÛıÂÓÂ›˜ Ô˘ ¤¯Ô˘Ó ˘Ô‚ÏËıÂ› ÛÂ Â¤Ì‚·ÛË ·ÚÙËÚÈ·Î‹˜ ·ÓÙÈÌÂÙ¿ıÂÛË˜ (arterial switch operation) ÂÈÙÚ¤ÔÓÙ·È fiÏ· Ù· ·ıÏ‹Ì·Ù· fiÙ·Ó ÙÔ Ì¤ÁÂıÔ˜ Î·È Ë Û˘ÛÙ·ÏÙÈÎfiÙËÙ· ÙË˜ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ¿, ‰ÂÓ ˘¿Ú¯Ô˘Ó ˘ÔÏÂÈfiÌÂÓÂ˜ ·ÓˆÌ·Ï›Â˜, Ë ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ‹ Î·È ‰ÂÓ ‰È·ÈÛÙÒÓÔÓÙ·È ÛËÌ·ÓÙÈÎ¤˜ ·ÚÚ˘ıÌ›Â˜ ÛÙÔ Holter Ú˘ıÌÔ‡. ∂ÂÈ‰‹ ˘¿Ú¯ÂÈ ÙÔ ıÂˆÚËÙÈÎfi ÂÓ‰Â¯fiÌÂÓÔ ÂÈ‚¿Ú˘ÓÛË˜ ÙË˜ ÓÂÔ·ÔÚÙÈÎ‹˜ Ú›˙·˜, Û˘ÓÈÛÙ¿Ù·È ·ÔÊ˘Á‹ ÙˆÓ ·ıÏËÌ¿ÙˆÓ Î·ÙËÁÔÚ›·˜ πππ. ŸÛÔÈ ·ÛıÂÓÂ›˜ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‹ÈÂ˜ ·ÈÌÔ‰˘Ó·ÌÈÎ¤˜ ‰È·Ù·Ú·¯¤˜ ‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙË˜ ·ÚÈÛÙÂÚ‹˜ ÎÔÈÏ›·˜, ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙÈ˜ Î·ÙËÁÔÚ›Â˜ π Î·È ππ∞ ÂÊfiÛÔÓ Ë ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ‹. ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

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™Â ·ÛıÂÓÂ›˜ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙÂ› ‰ÈfiÚıˆÛË ÌÂ ÙÈ˜ ·Ï·ÈfiÙÂÚÂ˜ ÙÂ¯ÓÈÎ¤˜ (Mustard ‹ Senning) Ù· ÚÔ‚Ï‹Ì·Ù· Â›Ó·È ÂÚÈÛÛfiÙÂÚ·, Î·ıÒ˜ ÚfiÏÔ Û˘ÛÙËÌ·ÙÈÎ‹˜ ÎÔÈÏ›·˜ ‰È·‰Ú·Ì·Ù›˙ÂÈ Ë ‰ÂÍÈ¿ ÎÔÈÏ›·. ™ÙÈ˜ ÂÚÈÙÒÛÂÈ˜ ·˘Ù¤˜ ÂÈÙÚ¤ÂÙ·È Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ıÏ‹Ì·Ù· Ù‡Ô˘ π∞ Î·È ππ∞, ·Ó ˘¿Ú¯Ô˘Ó ÔÈ ÂÍ‹˜ ÚÔ¸Ôı¤ÛÂÈ˜: Ê˘ÛÈÔÏÔÁÈÎfi Ì¤ÁÂıÔ˜ ÎÔÈÏÔÙ‹ÙˆÓ, ·Ô˘Û›· ·ÚÚ˘ıÌÈÒÓ, ·Ô˘Û›· ÈÛÙÔÚÈÎÔ‡ Û˘ÁÎÔÙÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ Î·È Ê˘ÛÈÔÏÔÁÈÎ‹ ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜. ™‡ÌÏÔÎÂ˜ Î˘·ÓˆÙÈÎ¤˜ Î·Ú‰ÈÔ¿ıÂÈÂ˜ (ÌÂÙ¿ ·fi ·ÚËÁÔÚËÙÈÎ‹ Â¤Ì‚·ÛË): ¶ÚfiÎÂÈÙ·È ÁÈ· ÌÈ· ÌÂÁ¿ÏË Î·È ·ÓÔÌÔÈÔÁÂÓ‹ ÔÌ¿‰· ·ı‹ÛÂˆÓ, ÙˆÓ ÔÔ›ˆÓ ÎÔÈÓfi ¯·Ú·ÎÙËÚÈÛÙÈÎfi Â›Ó·È Ô ¯·ÌËÏfi˜ ÎÔÚÂÛÌfi˜ ÛÂ ÔÍ˘ÁfiÓÔ ÙÔ˘ ·ÚÙËÚÈ·ÎÔ‡ ·›Ì·ÙÔ˜. √È ÂÚÈÛÛfiÙÂÚÔÈ ·fi ÙÔ˘˜ ·ÛıÂÓÂ›˜ ·˘ÙÔ‡˜ ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ Î·ÙËÁÔÚ›· π∞ Î·È ÔÚÈÛÌ¤ÓÔÈ ·fi ·˘ÙÔ‡˜ Î·È ÛÙËÓ Î·ÙËÁÔÚ›· πµ, ·Ó ¤¯Ô˘Ó Ê˘ÛÈÔÏÔÁÈÎfi ÎÔÚÂÛÌfi Î·È ÈÎ·ÓÔÔÈËÙÈÎ‹ ÎÔÈÏÈ·Î‹ ÏÂÈÙÔ˘ÚÁ›· ¯ˆÚ›˜ ·ÚÚ˘ıÌ›Â˜. ™˘ÁÁÂÓÂ›˜ ·ÓˆÌ·Ï›Â˜ ÛÙÂÊ·ÓÈ·›ˆÓ ·ÚÙËÚÈÒÓ: ¶Ú¤ÂÈ Ó· ÙÈ˜ ˘Ô„È¿˙ÂÙ·È Î·ÓÂ›˜ ÛÂ ÓÂ·ÚÔ‡˜ ·ıÏËÙ¤˜ ÌÂ ÚÔÎ¿Ú‰ÈÔ ¿ÏÁÔ˜ ‹ Û˘ÁÎÔÙÈÎfi ÂÂÈÛfi‰ÈÔ Î·Ù¿ ÙËÓ ¿ÛÎËÛË. ŒÍÈ Ì‹ÓÂ˜ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈÎ‹ ·ÔÎ·Ù¿ÛÙ·ÛË ÂÈÙÚ¤ÂÙ·È Ë ¿ıÏËÛË, ·Ó Ë Ì¤ÁÈÛÙË ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎ‹ Î·È ‰ÂÓ ¤¯ÂÈ ÚÔ¸¿ÚÍÂÈ ¤ÌÊÚ·ÁÌ· Ì˘ÔÎ·Ú‰›Ô˘. ™‡Ó‰ÚÔÌÔ Marfan: √È ·ÛıÂÓÂ›˜ ·˘ÙÔ› ÎÈÓ‰˘ÓÂ‡Ô˘Ó ·fi ‰È·¯ˆÚÈÛÙÈÎfi ·ÓÂ‡Ú˘ÛÌ· ÙË˜ ·ÔÚÙ‹˜ (10) Î·È ··ÁÔÚÂ‡ÂÙ·È Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ ·ıÏ‹Ì·Ù· ÌÂ Î›Ó‰˘ÓÔ ÛˆÌ·ÙÈÎ‹˜ ÚfiÛÎÚÔ˘ÛË˜ (¶›Ó·Î·˜ 2). ∞Ó ‰ÂÓ ˘¿Ú¯ÂÈ ‰È¿Ù·ÛË ·ÔÚÙ‹˜ Î·È ·ÓÂ¿ÚÎÂÈ· ÌÈÙÚÔÂÈ‰Ô‡˜, ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ ·ıÏ‹Ì·Ù· Î·ÙËÁÔÚ›·˜ π∞, ÙÔÍÔ‚ÔÏ›·, Ù¤ÓÈ˜ ‰ÈÏfi, ÛÙ·ÙÈÎfi Ô‰‹Ï·ÙÔ Î·È ·ÙÈÓ¿˙ Â› ¿ÁÔ˘ (11). √ Ë¯ÔÎ·Ú‰ÈÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÈ‚¿ÏÏÂÙ·È ·Ó¿ ÂÍ¿ÌËÓÔ. ¶ÚfiÙˆÛË ÌÈÙÚÔÂÈ‰Ô‡˜ (12): ∏ ÚfiÙˆÛË ÙË˜ ÌÈÙÚÔÂÈ‰Ô‡˜ Â›Ó·È È‰È·›ÙÂÚ· Û˘¯Ó‹ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, ÌÂ ÙË Û˘¯ÓfiÙËÙ¿ ÙË˜ Ó· Î˘Ì·›ÓÂÙ·È ·fi 2-5% (13). ™˘Ó‹ıˆ˜ ÚfiÎÂÈÙ·È ÁÈ· Î·ÏÔ‹ıË Î·Ù¿ÛÙ·ÛË, ·Ó Î·È ÛÂ ÔÚÈÛÌ¤ÓÂ˜ ÂÚÈÙÒÛÂÈ˜ Û˘ÓÔ‰Â‡ÂÙ·È ·fi ·›ÛıËÌ· ÚÔÎ·Ú‰›ˆÓ ·ÏÌÒÓ, ˙¿ÏË Î·È ˘ÂÚÎÔÈÏÈ·Î¤˜ ‹ ÎÔÈÏÈ·Î¤˜ ·ÚÚ˘ıÌ›Â˜ (14). ªÔÚÂ› Ó· ·ÔÙÂÏ¤ÛÂÈ ÙÔ ·›ÙÈÔ ÛËÌ·ÓÙÈÎ‹˜ ÌÈÙÚÔÂÈ‰ÈÎ‹˜ ·ÓÂ¿ÚÎÂÈ·˜, ÂÌ‚ÔÏÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ Î·È ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ (15). ¶ÈÛÙÂ‡ÂÙ·È fiÙÈ ÔÈ ÛÔ‚·Ú¤˜ ÂÈÏÔÎ¤˜ Û¯ÂÙ›˙ÔÓÙ·È ÌÂ ÙË ÌÔÚÊ‹ ÙË˜ ÓfiÛÔ˘ ÛÙËÓ ÔÔ›· ÔÈ ÌÔÚÊÔÏÔÁÈÎ¤˜ ·ÏÏÔÈÒÛÂÈ˜ ÙˆÓ ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

ÁÏˆ¯›ÓˆÓ Â›Ó·È ¤Î‰ËÏÂ˜ (13). ™Â ÁÂÓÈÎ¤˜ ÁÚ·ÌÌ¤˜, Ë ÚfiÁÓˆÛË ÁÈ· ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ÚfiÙˆÛË Â›Ó·È Â˘ÓÔ˚Î‹ Î·È Ù· ÂÂÈÛfi‰È· ·ÈÊÓ›‰ÈˆÓ ı·Ó¿ÙˆÓ Ô˘ ¤¯Ô˘Ó ·Ó·ÊÂÚıÂ› Â›Ó·È ÔÏ‡ Û¿ÓÈ· (16). ŒÙÛÈ, ·ÛıÂÓÂ›˜ ÌÂ ÚfiÙˆÛË ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·, ÌÂ Èı·Ó‹ ÂÍ·›ÚÂÛË ·˘Ù¿ ÙË˜ Î·ÙËÁÔÚ›·˜ πππ, ·Ó ‰ÂÓ ˘¿Ú¯Ô˘Ó Ù· ÂÍ‹˜: ·) ÈÛÙÔÚÈÎfi Û˘ÁÎÔÙÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ ·ÚÚ˘ıÌÈÔÏÔÁÈÎ‹˜ ÚÔ¤ÏÂ˘ÛË˜, ‚) ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ Ô˘ Û¯ÂÙ›˙ÂÙ·È ÌÂ ÚfiÙˆÛË ÌÈÙÚÔÂÈ‰Ô‡˜, Á) Â·Ó·Ï·Ì‚·ÓfiÌÂÓ· ÂÂÈÛfi‰È· ˘ÂÚÎÔÈÏÈ·Î‹˜ Ù·¯˘Î·Ú‰›·˜ ‹ Û‡ÌÏÔÎÂ˜ ÌÔÚÊ¤˜ ÎÔÈÏÈ·ÎÒÓ ·ÚÚ˘ıÌÈÒÓ, ÂÈ‰ÈÎ¿ ·Ó ÂÈ‰ÂÈÓÒÓÔÓÙ·È ÌÂ ÙËÓ ¿ÛÎËÛË, ‰) ÛËÌ·ÓÙÈÎ‹ ·ÓÂ¿ÚÎÂÈ· ÌÈÙÚÔÂÈ‰Ô‡˜ Î·È Â) ÚÔËÁËı¤Ó ÂÌ‚ÔÏÈÎfi ÂÂÈÛfi‰ÈÔ. ŸÙ·Ó ˘¿Ú¯ÂÈ Î¿ÔÈÔ ·fi Ù· ·Ú·¿Óˆ Â˘Ú‹Ì·Ù· ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÙËÓ Î·ÙËÁÔÚ›· π∞. ª˘ÔÎ·Ú‰ÈÔ¿ıÂÈÂ˜ – ª˘ÔÎ·Ú‰›ÙÈ‰· – ¶ÂÚÈÎ·Ú‰›ÙÈ‰· (12) ÀÂÚÙÚÔÊÈÎ‹ Ì˘ÔÎ·Ú‰ÈÔ¿ıÂÈ·: Ÿˆ˜ Â›Ó·È ÁÓˆÛÙfi Ë ˘ÂÚÙÚÔÊÈÎ‹ Ì˘ÔÎ·Ú‰ÈÔ¿ıÂÈ· ·ÔÙÂÏÂ› ÙËÓ Î‡ÚÈ· ·ÈÙ›· ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ Î·Ù¿ ÙËÓ ¿ÛÎËÛË ÛÂ ÓÂ·Ú¿ ¿ÙÔÌ· (17). °È· ÙÔÓ ÏfiÁÔ ·˘Ùfi, fiÙ·Ó Ë ‰È¿ÁÓˆÛË ÙË˜ Â›Ó·È Û›ÁÔ˘ÚË, ··ÁÔÚÂ‡ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÙˆÓ ·Û¯fiÓÙˆÓ ÛÂ ÔÔÈÔ‰‹ÔÙÂ ·ÓÙ·ÁˆÓÈÛÙÈÎfi ¿ıÏËÌ·. ™Â ÔÚÈÛÌ¤Ó· ¿ÙÔÌ· ÛÙ· ÔÔ›· Ë ‰È¿ÁÓˆÛË ¤¯ÂÈ ÙÂıÂ› ÌÂ ÁÂÓÂÙÈÎfi ¤ÏÂÁ¯Ô (18) ¯ˆÚ›˜ Ó· ¤¯ÂÈ ·ÎfiÌ· ÂÎ‰ËÏˆıÂ› Ê·ÈÓÔÙ˘ÈÎ¿ Ë ÓfiÛÔ˜, ‰ÂÓ ˘¿Ú¯Ô˘Ó Â› ÙÔ˘ ·ÚfiÓÙÔ˜ ÛÙÔÈ¯Â›· Ô˘ Ó· ·ÔÎÏÂ›Ô˘Ó ÙË Û˘ÌÌÂÙÔ¯‹ ÙÔ˘˜ ÛÂ ·ıÏËÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜, ÂÎÙfi˜ ·Ó ˘¿Ú¯Ô˘Ó Û˘ÌÙÒÌ·Ù· ‹ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘. ∂›ÛË˜, Û‡ÌÊˆÓ· ÌÂ ÙÈ˜ ÙÂÏÂ˘Ù·›Â˜ Ô‰ËÁ›Â˜ ÙË˜ ∞merican ∏eart ∞ssociation (11), ¿ÙÔÌ· ¿Û¯ÔÓÙ· ·fi ÙË ÓfiÛÔ ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ ÌË ·ÓÙ·ÁˆÓÈÛÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜, fiˆ˜ Ô‰ËÏ·Û›·, ÎÔÏ‡Ì‚ËÛË, Ù¤ÓÈ˜ ‰ÈÏfi, ÌfiÔ˘ÏÈÓÁÎ, ÁÎÔÏÊ Î·È ·ÙÈÓ¿˙ Â› ¿ÁÔ˘. ª˘ÔÎ·Ú‰›ÙÈ‰·: ∏ Ì˘ÔÎ·Ú‰›ÙÈ‰·, Û˘Ó‹ıˆ˜ ÈÔÁÂÓÔ‡˜ ·ÈÙÈÔÏÔÁ›·˜, ıÂˆÚÂ›Ù·È Û¿ÓÈÔ ·›ÙÈÔ ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ Î·Ù¿ ÙËÓ ¿ÛÎËÛË (1). ¶·ÚfiÏ· ·˘Ù¿ Â›Ó·È ÛËÌ·ÓÙÈÎ‹ ·fi ÎÏÈÓÈÎ‹˜ ·fi„Âˆ˜, ‰ÈfiÙÈ Â›Ó·È ‰˘Ó·Ùfi Ó· ‰È·‰Ú¿ÌÂÈ ˘ÔÎÏÈÓÈÎ¿, ¯ˆÚ›˜ ıÔÚ˘‚Ò‰Ë Û˘ÌÙˆÌ·ÙÔÏÔÁ›· Î·È Ó· ·Ú·ÌÂ›ÓÂÈ ·‰È¿ÁÓˆÛÙË. ∞ÛıÂÓÂ›˜ Ô˘ ÈÛÙÂ‡ÂÙ·È fiÙÈ ¿Û¯Ô˘Ó ·fi Ì˘ÔÎ·Ú‰›ÙÈ‰· Ú¤ÂÈ Ó· ·¤¯Ô˘Ó ·fi Î¿ıÂ ·ıÏËÙÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ·

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ÁÈ· 6 Ì‹ÓÂ˜. ªÂÙ¿ ÙËÓ ¿ÚÔ‰Ô ÙË˜ ÂÚÈfi‰Ô˘ ·˘Ù‹˜, ÌÔÚÔ‡Ó Ó· ÂÈÛÙÚ¤„Ô˘Ó ÛÙÔÓ ·ıÏËÙÈÛÌfi ÂÊfiÛÔÓ ÔÈ ‰È·ÛÙ¿ÛÂÈ˜ Î·È Ë Û˘ÛÙ·ÏÙÈÎfiÙËÙ· ÙË˜ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜ ¤¯Ô˘Ó Â·Ó¤ÏıÂÈ ÛÂ Ê˘ÛÈÔÏÔÁÈÎ¿ Â›Â‰· Î·È ÛÙÔ Holter Ú˘ıÌÔ‡ ‰ÂÓ ˘¿Ú¯Ô˘Ó ÂÂÈÛfi‰È· ÂÈÌ¤ÓÔ˘Û·˜ ˘ÂÚÎÔÈÏÈ·Î‹˜ Ù·¯˘Î·Ú‰›·˜ ‹ Û‡ÌÏÔÎÂ˜ ÌÔÚÊ¤˜ ÎÔÈÏÈ·ÎÒÓ ·ÚÚ˘ıÌÈÒÓ. ¶ÂÚÈÎ·Ú‰›ÙÈ‰·: ∫·Ù¿ ÙËÓ ÔÍÂ›· Ê¿ÛË ÙË˜ ÓfiÛÔ˘ ··ÁÔÚÂ‡ÂÙ·È Î¿ıÂ ·ıÏËÙÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ·. ∏ ¿ıÏËÛË ÂÈÙÚ¤ÂÙ·È ¿ÏÈ, fiÙ·Ó ÙÔ ˘ÁÚfi ¤¯ÂÈ ·ÔÚÚÔÊËıÂ› Ï‹Úˆ˜, ÔÈ ÂÚÁ·ÛÙËÚÈ·ÎÔ› ‰Â›ÎÙÂ˜ ÏÔ›ÌˆÍË˜ ¤¯Ô˘Ó ˘Ô¯ˆÚ‹ÛÂÈ Î·È ÙÔ ∏olter Ú˘ıÌÔ‡ Â›Ó·È Ê˘ÛÈÔÏÔÁÈÎfi. ∞Ó Û˘Ó˘¿Ú¯ÂÈ ÚÔÛ‚ÔÏ‹ ÙÔ˘ Ì˘ÔÎ·Ú‰›Ô˘, ÙfiÙÂ ·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÔÈ Ô‰ËÁ›Â˜ Ô˘ ·ÊÔÚÔ‡Ó ÙË Ì˘ÔÎ·Ú‰›ÙÈ‰·. ¡fiÛÔ˜ Kawasaki ∞ÔÙÂÏÂ› ÙÔ Û˘¯ÓfiÙÂÚÔ ·›ÙÈÔ Â›ÎÙËÙË˜ ÛÙÂÊ·ÓÈ·›·˜ ÓfiÛÔ˘ ÛÙËÓ ·È‰ÈÎ‹ ËÏÈÎ›· (19). ¶ÚfiÎÂÈÙ·È ÁÈ· ÌÈ· ‰È¿¯˘ÙË ÊÏÂÁÌÔÓÒ‰Ë ÌÈÎÚÔ·ÁÁÂÈ›ÙÈ‰· Ô˘ ÌÔÚÂ› Ó· ÚÔÛ‚¿ÏÂÈ ÙÈ˜ ÛÙÂÊ·ÓÈ·›Â˜ ·ÚÙËÚ›Â˜ Î·È Ó· ÚÔÎ·Ï¤ÛÂÈ ·ÓÂ˘Ú‡ÛÌ·Ù· Î·È ÛÙÂÓÒÛÂÈ˜ ÔÈ ÔÔ›Â˜ ‰˘Ó·Ùfi Ó· ÂÎ‰ËÏˆıÔ‡Ó ÎÏÈÓÈÎ¿, ÔÏÏ¿ ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ ·Ú¯ÈÎ‹ ÚÔÛ‚ÔÏ‹ (20,21). ∆· ·ÓÂ˘Ú‡ÛÌ·Ù· Û˘Ó‹ıˆ˜ ‰È·ÁÈÁÓÒÛÎÔÓÙ·È Â·ÚÎÒ˜ ÌÂ ÙÔ Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ·, ·ÏÏ¿ ÁÈ· ÙËÓ ·Ó›¯ÓÂ˘ÛË ÙË˜ Ì˘ÔÎ·Ú‰È·Î‹˜ ÈÛ¯·ÈÌ›·˜ ‰ÂÓ ·ÚÎÂ› Ë ·Ï‹ ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È Û˘Ó‹ıˆ˜ ··ÈÙÂ›Ù·È Î·È ÎfiˆÛË ÌÂ ı¿ÏÏÈÔ. ∞ÛıÂÓÂ›˜ ¯ˆÚ›˜ ÚÔÛ‚ÔÏ‹ ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ ÌÔÚÔ‡Ó Ó· ·ıÏÔ‡ÓÙ·È ÂÏÂ‡ıÂÚ· ÌÂÙ¿ ·fi 6-8 Â‚‰ÔÌ¿‰Â˜. ∞ÛıÂÓÂ›˜ Ô˘ Â›¯·Ó ·ÓÂ˘Ú‡ÛÌ·Ù· Ô˘ ÂÍ·Ê·Ó›ÛıËÎ·Ó Ú¤ÂÈ Ó· ÂÏ¤Á¯ÔÓÙ·È ÚÒÙ· ÌÂ ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È ÛÈÓıËÚÔÁÚ¿ÊËÌ· ·ÈÌ¿ÙˆÛË˜ ÙÔ˘ Ì˘ÔÎ·Ú‰›Ô˘. ∞ÛıÂÓÂ›˜ ÌÂ ÌÈÎÚ¿ ·ÓÂ˘Ú‡ÛÌ·Ù· Û˘ÌÌÂÙ¤¯Ô˘Ó Ì¤¯ÚÈ ÙËÓ Î·ÙËÁÔÚ›· ππµ, ·ÊÔ‡ ÚÔËÁÔ˘Ì¤Óˆ˜ ÂÏÂÁ¯ıÔ‡Ó ÁÈ· ÈÛ¯·ÈÌ›·, ÂÓÒ ·ÛıÂÓÂ›˜ ÌÂ ÌÂÁ¿Ï· ·ÓÂ˘Ú‡ÛÌ·Ù· ‹ ÛÙÂÓÒÛÂÈ˜ Î·Ù·Ù¿ÛÛÔÓÙ·È ÛÙËÓ Î·ÙËÁÔÚ›· π∞. ∞ÚÚ˘ıÌ›Â˜ (22) ŒÎÙ·ÎÙÂ˜ ÎÔÈÏÈ·Î¤˜ Û˘ÛÙÔÏ¤˜ (∂∫™): √ ¤ÏÂÁ¯Ô˜ ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ ÂÚÈÏ·Ì‚¿ÓÂÈ, ÂÎÙfi˜ ·fi ÙÔ ∏∫° 12 ··ÁˆÁÒÓ, ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ· ÁÈ· ÙÔÓ ·ÔÎÏÂÈÛÌfi ‰ÔÌÈÎ‹˜ Î·Ú‰ÈÔ¿ıÂÈ·˜. ∞Ó ÛÙË ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ ·˘Í¿ÓÂÙ·È Ô ·ÚÈıÌfi˜ ÙˆÓ ÂÎÙ¿ÎÙˆÓ ‹ Î·ı›ÛÙ·ÓÙ·È Û‡ÌÏÔÎÂ˜, ÙfiÙÂ ÂÈ‚¿ÏÏÂÙ·È ÂÚ·ÈÙ¤Úˆ ¤ÏÂÁ¯Ô˜, ÂÓ‰Â¯ÔÌ¤Óˆ˜ Î·È ÌÂ Î·Ú‰È·Îfi Î·ıÂÙËÚÈ·ÛÌfi, ·ÎfiÌ· Î·È ·Ó ‰ÂÓ ˘¿Ú¯ÂÈ

ÂÌÊ·Ó‹˜ ‰ÔÌÈÎ‹ Î·Ú‰ÈÔ¿ıÂÈ· ÛÙÔ Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ·. ŸÙ·Ó ÔÈ ∂∫™ ÂÍ·Ê·Ó›˙ÔÓÙ·È ‹ ÌÂÈÒÓÔÓÙ·È ÌÂ ÙËÓ ÎfiˆÛË Î·È ‰ÂÓ ˘¿Ú¯ÂÈ ˘ÔÎÂ›ÌÂÓË Î·Ú‰ÈÔ¿ıÂÈ·, Ë Û˘ÌÌÂÙÔ¯‹ Â›Ó·È ÂÏÂ‡ıÂÚË. ŸÙ·Ó ˘¿Ú¯ÂÈ ‰ÔÌÈÎ‹ Î·Ú‰ÈÔ¿ıÂÈ· ‹ Ô ·ÛıÂÓ‹˜ ¯Ú‹˙ÂÈ ÁÈ· ÔÔÈÔÓ‰‹ÔÙÂ ÏfiÁÔ ·ÓÙÈ·ÚÚ˘ıÌÈÎ‹˜ ·ÁˆÁ‹˜, ÙfiÙÂ ÂÈÙÚ¤ÔÓÙ·È ÌfiÓÔ Ù· ·ıÏ‹Ì·Ù· Î·ÙËÁÔÚ›·˜ π∞. ÀÂÚÎÔÈÏÈ·Î‹ Ù·¯˘Î·Ú‰›·: ∞ÔÙÂÏÂ› Ì›· ·fi ÙÈ˜ Ï¤ÔÓ Û˘¯Ó¤˜ ·ÚÚ˘ıÌ›Â˜ ÛÙ· ·È‰È¿. ™Â ÁÂÓÈÎ¤˜ ÁÚ·ÌÌ¤˜, Ë Û˘ÌÌÂÙÔ¯‹ ÛÙËÓ ¿ıÏËÛË Â›Ó·È ÂÏÂ‡ıÂÚË ÂÊfiÛÔÓ ÔÈ ·ÛıÂÓÂ›˜ Â›Ó·È ·Û˘ÌÙˆÌ·ÙÈÎÔ› Î·È Ë ·ÓÙÈ·ÚÚ˘ıÌÈÎ‹ ·ÁˆÁ‹ ÚfiÏË„Ë˜ ÙˆÓ ˘ÔÙÚÔÒÓ Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈÎ‹, fiˆ˜ ÂÏ¤Á¯ÂÙ·È ÌÂ ÙÔ ∏∫° 24ÒÚÔ˘ Î·È ÙË ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜. ∞Ó ˘¿Ú¯Ô˘Ó ÛÔ‚·Ú¿ Û˘ÌÙÒÌ·Ù· (Û˘ÁÎÔÙÈÎ¿ ‹ ÚÔÛ˘ÁÎÔÙÈÎ¿ ÂÂÈÛfi‰È·, ¤ÓÙÔÓÔ ·›ÛıËÌ· ÚÔÎ·Ú‰›ˆÓ ·ÏÌÒÓ), ÙfiÙÂ Ë ¿ıÏËÛË ÂÈÙÚ¤ÂÙ·È ÂÏÂ‡ıÂÚ· ÌÂÙ¿ ·fi 6 Ì‹ÓÂ˜ ·Ô˘Û›·˜ ˘ÔÙÚÔÒÓ. ª¤¯ÚÈ ÙfiÙÂ ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ Î·ÙËÁÔÚ›· π∞. ªÂÙ¿ ·fi Î·Ù¿Ï˘ÛË ÌÂ Î·ıÂÙ‹Ú· ÂÈÙÚ¤ÂÙ·È ÂÏÂ‡ıÂÚ· Ë ¿ıÏËÛË ÌÂÙ¿ ¿ÚÔ‰Ô 2 ÌËÓÒÓ Î·È ÂÊfiÛÔÓ ÛÙÔ ÌÂÛÔ‰È¿ÛÙËÌ· ‰ÂÓ ˘‹ÚÍ·Ó ˘ÔÙÚÔ¤˜. ™‡Ó‰ÚÔÌÔ WPW: √ ·ÈÊÓ›‰ÈÔ˜ ı¿Ó·ÙÔ˜ Â›Ó·È ÁÂÓÈÎ¿ Û¿ÓÈÔ Ê·ÈÓfiÌÂÓÔ ÛÂ ·ıÏËÙ¤˜ ÌÂ Û‡Ó‰ÚÔÌÔ ÚÔ‰È¤ÁÂÚÛË˜ Î·È Ê·›ÓÂÙ·È Ó· ÂÚÈÔÚ›˙ÂÙ·È ÛÂ ·ÛıÂÓÂ›˜ ÌÂ ‚Ú·¯Â›· ·ÓÂÚ¤ıÈÛÙË ÂÚ›Ô‰Ô ÙÔ˘ ·Ú·ÏËÚˆÌ·ÙÈÎÔ‡ ‰ÂÌ·Ù›Ô˘ (23,24). √ ÚÔ·ıÏËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÚÈÏ·Ì‚¿ÓÂÈ ÔˆÛ‰‹ÔÙÂ ∏∫° 12 ··ÁˆÁÒÓ, 24ˆÚË Î·Ù·ÁÚ·Ê‹ ÙÔ˘ Ú˘ıÌÔ‡, Ë ÔÔ›· Î·Ïfi Â›Ó·È Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ Î·È ÙËÓ ·ıÏËÙÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ· ÙÔ˘ ·ÛıÂÓÔ‡˜, Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ· Î·È ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜. ∂ÎÙfi˜ ·fi ÙÈ˜ ÚÔ·Ó·ÊÂÚıÂ›ÛÂ˜ ÂÍÂÙ¿ÛÂÈ˜, ÔÏÏÔ› ı· Û˘ÓÈÛÙÔ‡Û·Ó Î·È ËÏÂÎÙÚÔÊ˘ÛÈÔÏÔÁÈÎ‹ ÌÂÏ¤ÙË ÛÂ ¿ÙÔÌ· ËÏÈÎ›·˜ Î¿Ùˆ ÙˆÓ 20 ÂÙÒÓ. ªÂÙ¿ ·fi ÂÈÙ˘¯‹ Î·Ù¿Ï˘ÛË ÌÂ Î·ıÂÙ‹Ú· ÙÔ˘ ·Ú·ÏËÚˆÌ·ÙÈÎÔ‡ ‰ÂÌ·Ù›Ô˘, ÂÈÙÚ¤ÂÙ·È Ë ¿ıÏËÛË ÂÏÂ‡ıÂÚ· ÌÂÙ¿ ¿ÚÔ‰Ô 2 ÌËÓÒÓ, ·Ó ‰ÂÓ ˘¿Ú¯ÂÈ ÂÈÎfiÓ· ÚÔ‰È¤ÁÂÚÛË˜ ÛÙÔ ∏∫°. ™‡Ó‰ÚÔÌÔ Ì·ÎÚÔ‡ QT: ∞ÔÙÂÏÂ› Û¿ÓÈÔ ·›ÙÈÔ ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘. £ÂˆÚÂ›Ù·È ·Ú·ÙÂÙ·Ì¤ÓÔ fiÙ·Ó ÙÔ ‰ÈÔÚıˆÌ¤ÓÔ QT Â›Ó·È ÌÂÁ·Ï‡ÙÂÚÔ ÙˆÓ 460 msec (25). ªÂ ÙËÓ ÂÎÙÂÙ·Ì¤ÓË ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÚÔ·ıÏËÙÈÎÔ‡ ÂÏ¤Á¯Ô˘ ı· ˘¿ÚÍÔ˘Ó ·ÚÎÂÙ¿ ¿ÙÔÌ· Ù· ÔÔ›· ı· ÂÌÊ·Ó›˙Ô˘Ó ÔÚÈ·Î‹ ·‡ÍËÛË ÙÔ˘ QTc, ÌÂ ·ÔÙ¤ÏÂÛÌ· Ó· Á›ÓÂÙ·È ˘ÂÚ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘. ™ÙÔ˘˜ ·ıÏËÙ¤˜ ·˘ÙÔ‡˜, fiÙ·Ó Â›Ó·È ·Û˘ÌÙˆÌ·ÙÈÎÔ›, ¤¯Ô˘Ó ÂÏÂ‡ıÂÚÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi, Ê˘ÛÈÔÏÔÁÈÎfi Î·Ù¿ ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

474

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Ù· ¿ÏÏ· ∏∫° Î·È Ê˘ÛÈÔÏÔÁÈÎ‹ ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜, ‰ÂÓ ÂÈ‚¿ÏÏÔÓÙ·È ÂÚÈÔÚÈÛÌÔ›. ™Â ¿ÙÔÌ· ÌÂ ÂÈ‚Â‚·ÈˆÌ¤ÓË ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Ì·ÎÚÔ‡ QT ··ÁÔÚÂ‡ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ÓÙ·ÁˆÓÈÛÙÈÎ¿ ·ıÏ‹Ì·Ù·, ÌÔÚÔ‡Ó fiÌˆ˜ Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ „˘¯·ÁˆÁÈÎ¤˜ ·ıÏËÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜ (Ù¤ÓÈ˜ ‰ÈÏfi, ÛÙ·ÙÈÎfi Ô‰‹Ï·ÙÔ, ÌfiÔ˘ÏÈÓÁÎ, ÁÎÔÏÊ Î·È ·ÙÈÓ¿˙ Â› ¿ÁÔ˘) (11). ∂Í·›ÚÂÛË ·ÔÙÂÏÔ‡Ó ÔÈ ÂÚÈÙÒÛÂÈ˜ ÙÔ˘ Ì·ÎÚÔ‡ QT Ù‡Ô˘ 1 ÛÙÔ ÔÔ›Ô ··ÁÔÚÂ‡ÂÙ·È Ë ÎÔÏ‡Ì‚ËÛË ·ÎfiÌ· Î·È ÁÈ· „˘¯·ÁˆÁÈÎÔ‡˜ ÏfiÁÔ˘˜. ¶¿ÓÙˆ˜, ÂÂÈ‰‹ ÙÔ Û‡Ó‰ÚÔÌÔ ·ÚÔ˘ÛÈ¿˙ÂÈ ·ÚÎÂÙ¤˜ ·Ú·ÏÏ·Á¤˜, Î·Ïfi Â›Ó·È Â› ˘Ô„›·˜ ¤ÛÙˆ ˘¿ÚÍÂÒ˜ ÙÔ˘ Ó· Á›ÓÂÙ·È ÂÎÙ›ÌËÛË Î·È Î·ıÔ‰‹ÁËÛË ·fi ÂÈ‰ÈÎÔ‡˜. ∫ÔÏÔÎÔÈÏÈ·Îfi˜ ·ÔÎÏÂÈÛÌfi˜ 1Ô˘ ‚·ıÌÔ‡: ∞Ó ÙÔ QRS Â›Ó·È ·ıÔÏÔÁÈÎfi ‹ ÙÔ PR >300 msec, Û˘ÓÈÛÙ¿Ù·È Holter Ú˘ıÌÔ‡, ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È ÂÓ‰Â¯ÔÌ¤Óˆ˜ Î·È ËÏÂÎÙÚÔÊ˘ÛÈÔÏÔÁÈÎ‹ ÌÂÏ¤ÙË. ŸÙ·Ó Ô ·ÔÎÏÂÈÛÌfi˜ ‰ÂÓ ÂÈ‰ÂÈÓÒÓÂÙ·È ÌÂ ÙËÓ ¿ÛÎËÛË, ÙfiÙÂ Ë Û˘ÌÌÂÙÔ¯‹ Â›Ó·È ÂÏÂ‡ıÂÚË ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·. ∫ÔÏÔÎÔÈÏÈ·Îfi˜ ·ÔÎÏÂÈÛÌfi˜ 2Ô˘ ‚·ıÌÔ‡ (Ù‡Ô˘ 1): ∞·ÓÙ¿Ù·È Û˘¯Ó¿ ÛÂ ·ıÏËÙ¤˜ ˘„ËÏÒÓ ÂÈ‰fiÛÂˆÓ (26). √ Û˘ÓÈÛÙÒÌÂÓÔ˜ ¤ÏÂÁ¯Ô˜ ÂÚÈÏ·Ì‚¿ÓÂÈ ÂÎÙfi˜ ·fi ÙÔ ∏∫° Î·È ÙÔ Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ·, ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È Holter Ú˘ıÌÔ‡. ∞Ó Û˘Ó˘¿Ú¯ÂÈ Î·È ·ÔÎÏÂÈÛÌfi˜ ÛÎ¤ÏÔ˘˜, ÙfiÙÂ Û˘ÓÈÛÙ¿Ù·È Î·È ËÏÂÎÙÚÔÊ˘ÛÈÔÏÔÁÈÎ‹ ÌÂÏ¤ÙË. ŸÙ·Ó Ô ·ÔÎÏÂÈÛÌfi˜ ‚ÂÏÙÈÒÓÂÙ·È ‹ ¤ÛÙˆ ‰ÂÓ ÂÈ‰ÂÈÓÒÓÂÙ·È Î·Ù¿ ÙËÓ ÎfiˆÛË ‹ ÙËÓ Â·Ó·ÊÔÚ¿, ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·. ∞ÓÙ›ıÂÙ·, fiÙ·Ó Ô ·ÔÎÏÂÈÛÌfi˜ ÚˆÙÔÂÌÊ·Ó›˙ÂÙ·È ‹ ÂÈ‰ÂÈÓÒÓÂÙ·È Î·Ù¿ ÙËÓ ÎfiˆÛË ‹ ÙËÓ Â·Ó·ÊÔÚ¿, ÙfiÙÂ Û˘ÓÈÛÙ¿Ù·È ËÏÂÎÙÚÔÊ˘ÛÈÔÏÔÁÈÎ‹ ÌÂÏ¤ÙË. ¶Ï‹ÚË˜ ÎÔÏÔÎÔÈÏ·Îfi˜ ·ÔÎÏÂÈÛÌfi˜: √ ¤ÏÂÁ¯Ô˜ Á›ÓÂÙ·È ÌÂ ∏∫°, Ë¯ÔÎ·Ú‰ÈÔÁÚ¿ÊËÌ·, ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ Î·È Holter Ú˘ıÌÔ‡. ŸÙ·Ó ‰ÂÓ ˘¿Ú¯ÂÈ ÈÛÙÔÚÈÎfi Û˘ÁÎÔÙÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ, Ù· QRS Â›Ó·È ÛÙÂÓ¿, Ë Î·Ú‰È·Î‹ Û˘¯ÓfiÙËÙ· Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 40-50/min Î·È ·˘Í¿ÓÂÙ·È ÌÂ ÙËÓ ÎfiˆÛË, Ë Î·Ú‰È¿ Â›Ó·È ·Ó·ÙÔÌÈÎ¿ Ê˘ÛÈÔÏÔÁÈÎ‹ ÌÂ Î·Ï‹ Û˘ÛÙÔÏÈÎ‹ ÏÂÈÙÔ˘ÚÁ›· Î·È ‰ÂÓ ˘¿Ú¯Ô˘Ó ¤ÎÙ·ÎÙÂ˜ ÎÔÈÏÈ·Î¤˜ Û˘ÛÙÔÏ¤˜ ‹ ÎÔÈÏÈ·Î‹ Ù·¯˘Î·Ú‰›· Î·Ù¿ ÙËÓ ÎfiˆÛË, ÙfiÙÂ ÂÈÙÚ¤ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ fiÏ· Ù· ·ıÏ‹Ì·Ù·. ™Â ·ÓÙ›ıÂÙË ÂÚ›ÙˆÛË Ú¤ÂÈ Ó· ÙÔÔıÂÙÂ›Ù·È ‚ËÌ·ÙÔ‰fiÙË˜ ÚÈÓ ÂÈÙÚ·Â› Ë ÂÓ·Û¯fiÏËÛË ÌÂ ·ÓÙ·ÁˆÓÈÛÙÈÎ¿ ·ıÏ‹Ì·Ù·, ÔfiÙÂ ··ÁÔÚÂ‡ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ıÏ‹Ì·Ù· ÌÂ Î›Ó‰˘ÓÔ ÛˆÌ·ÙÈÎ‹˜ ÚfiÛÎÚÔ˘ÛË˜ (¶›Ó·Î·˜ 2). ªÂÙ¿ ÙËÓ ÙÔÔı¤ÙËÛË ÙÔ˘ ‚ËÌ·ÙÔ‰fiÙË ÚÔËÁÂ›Ù·È ¿ÓÙ· ‰ÔÎÈÌ·Û›· ÎÔÒÛÂˆ˜ ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

ÒÛÙÂ Ó· ‰È·ÈÛÙˆıÂ› Î·Ù¿ fiÛÔÓ Ë Î·Ú‰È·Î‹ Û˘¯ÓfiÙËÙ· ÌÔÚÂ› Ó· ·˘ÍËıÂ› ÛÙÔ ÂÈı˘ÌËÙfi ÁÈ· ÙÔ Û˘ÁÎÂÎÚÈÌ¤ÓÔ ¿ıÏËÌ· Â›Â‰Ô. ∆· ›‰È· ÈÛ¯‡Ô˘Ó Î·È ÁÈ· ÙÔ˘˜ ·ÛıÂÓÂ›˜ ÌÂ ÎÔÏÔÎÔÈÏÈ·Îfi ·ÔÎÏÂÈÛÌfi 2Ô˘ ‚·ıÌÔ‡ Ù‡Ô˘ 2. À¤ÚÙ·ÛË ∞Ó Î·È ‰ÂÓ ¤¯Ô˘Ó ·Ó·ÊÂÚıÂ› ÂÂÈÛfi‰È· ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ ÛÂ ˘ÂÚÙ·ÛÈÎ¿ ¿ÙÔÌ·, ˘¿Ú¯ÂÈ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi Ë ÚÔÎ·Ù¿ÏË„Ë fiÙÈ Â›Ó·È ÂÎÙÂıÂÈÌ¤Ó· ÛÂ ·˘ÍËÌ¤ÓÔ Î›Ó‰˘ÓÔ ‰˘Û¿ÚÂÛÙˆÓ Û˘Ì‚·Ì¿ÙˆÓ, ÂÓÒ Â›Ó·È ·Ô‰Â‰ÂÈÁÌ¤ÓÔ fiÙÈ ˆÊÂÏÔ‡ÓÙ·È ·fi ÙËÓ Ù·ÎÙÈÎ‹ ¿ıÏËÛË (27). ™Ù· ·È‰È¿ Ë ‰Â˘ÙÂÚÔ·ı‹˜ ˘¤ÚÙ·ÛË Â›Ó·È ÈÔ Û˘¯Ó‹ ·’ fi,ÙÈ ÛÙÔ˘˜ ÂÓ‹ÏÈÎÂ˜ Î·È Â›Ó·È Â˘ÓfiËÙÔ fiÙÈ ÛÙÈ˜ ÂÚÈÙÒÛÂÈ˜ ·˘Ù¤˜ Ú¤ÂÈ Ó· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È ÙÔ ÚˆÙÔ·ı¤˜ ·›ÙÈÔ ÚÔÙÔ‡ ÂÈÙÚ·Â› Ë ÂÏÂ‡ıÂÚË Û˘ÌÌÂÙÔ¯‹ ÛÙËÓ ¿ıÏËÛË. ™ÙËÓ ÚˆÙÔ·ı‹ ˘¤ÚÙ·ÛË ‰ÂÓ Ù›ıÂÓÙ·È ÂÚÈÔÚÈÛÌÔ› ·Ó Â›Ó·È ‹ÈÔ˘ ‹ Ì¤ÙÚÈÔ˘ ‚·ıÌÔ‡ Î·È ‰ÂÓ ˘¿Ú¯ÂÈ ‚Ï¿‚Ë ÙˆÓ ÔÚÁ¿ÓˆÓ-ÛÙfi¯ˆÓ (¶›Ó·ÎÂ˜ 3,4,5,6). ™Â ÂÚÈÙÒÛÂÈ˜ ÛÔ‚·Ú‹˜ ˘¤ÚÙ·ÛË˜ ··ÁÔÚÂ‡ÂÙ·È Ë Û˘ÌÌÂÙÔ¯‹ ÛÂ ·ıÏ‹Ì·Ù· ÙË˜ Î·ÙËÁÔÚ›·˜ πππ. ∂›Ó·È ÁÓˆÛÙfi, fiÙÈ ·ÊÂÓfi˜ ÌÂÓ Ë ·ÚÙËÚÈ·Î‹ ˘¤ÚÙ·ÛË Û˘Ó‰˘¿˙ÂÙ·È Û˘¯Ó¿ ÌÂ ·‡ÍËÛË ÙÔ˘ ÛˆÌ·ÙÈÎÔ‡ ‚¿ÚÔ˘˜ Î·È ·ÊÂÙ¤ÚÔ˘ fiÙÈ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· fiÏÔ Î·È ÂÚÈÛÛfiÙÂÚ· ·È‰È¿ ÛÙÔÓ ·Ó·Ù˘ÁÌ¤ÓÔ ÎfiÛÌÔ Â›Ó·È ·¯‡Û·ÚÎ·. °È· Ù· ·È‰È¿ ·˘Ù¿ Â›Ó·È ÂÍ·ÈÚÂÙÈÎ¿ ÛËÌ·ÓÙÈÎfi Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ ÔÚÁ·ÓˆÌ¤ÓÂ˜ Î·È Ù·ÎÙÈÎ¤˜ ·ıÏËÙÈÎ¤˜ ‰Ú·ÛÙËÚÈfiÙËÙÂ˜, ÒÛÙÂ Ó· ÂÈÙ‡¯Ô˘Ó ÌÂ›ˆÛË ÙÔ˘ ÛˆÌ·ÙÈÎÔ‡ ÙÔ˘˜ ‚¿ÚÔ˘˜. ∆· ˘¤Ú‚·Ú· ·È‰È¿ Î·È ¤ÊË‚ÔÈ Ú¤ÂÈ Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ ·ıÏ‹Ì·Ù· Ù· ÔÔ›· ÏËÚÔ‡Ó ÙÈ˜ ·Ú·Î¿Ùˆ ÚÔ¸Ôı¤ÛÂÈ˜ ÒÛÙÂ Ó· ÂÈÙ˘Á¯¿ÓÂÙ·È ·ÚÓËÙÈÎfi ÂÓÂÚÁÂÈ·Îfi ÈÛÔ˙‡ÁÈÔ (28): ·) Ë ‰Ú·ÛÙËÚÈfiÙËÙ· Ú¤ÂÈ Ó· ÚÔÎ·ÏÂ› Î›ÓËÛË ÌÂÁ¿ÏˆÓ Ì˘˚ÎÒÓ ÔÌ¿‰ˆÓ (.¯. ‚¿‰ÈÛÌ·, ÙÚ¤ÍÈÌÔ, Ô‰ËÏ·Û›·, ÎÔÏ‡Ì‚ËÛË, ¯ÔÚfi˜), ‚) Ë È‰·ÓÈÎ‹ ‰È¿ÚÎÂÈ· ÙË˜ ¿ÛÎËÛË˜ Ú¤ÂÈ Ó· Â›Ó·È 30-45 ÏÂÙ¿ Î·ıËÌÂÚÈÓ¿, ÒÛÙÂ Ó· ÂÈÙ˘Á¯¿ÓÂÙ·È ·ÒÏÂÈ· 300 ÂÚ›Ô˘ ıÂÚÌ›‰ˆÓ. ∞˘Ùfi Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ÂÈÙÂ˘¯ıÂ› ·fi ÙËÓ ·Ú¯‹ ÛÙ· ˘¤Ú‚·Ú· ·È‰È¿ Î·È ÁÈ’ ·˘Ùfi Û˘ÓÈÛÙ¿Ù·È Ó· ·ıÏÔ‡ÓÙ·È ·Ú¯ÈÎ¿ 10 ÏÂÙ¿ ËÌÂÚËÛ›ˆ˜, Ù· ÔÔ›· ÛÙË Û˘Ó¤¯ÂÈ·, ÚÔÔ‰Â˘ÙÈÎ¿, ·˘Í¿ÓÔÓÙ·È, Á) Ó· ‰›‰ÂÙ·È ÛËÌ·Û›· ÛÙË ‰È¿ÚÎÂÈ· Î·È ÛÙË Û˘¯ÓfiÙËÙ· ÙË˜ ¿ÛÎËÛË˜ Î·È fi¯È ÛÙËÓ ¤ÓÙ·ÛË ÌÂ ÙËÓ ÔÔ›· ·˘Ù‹ ÂÎÙÂÏÂ›Ù·È (.¯. Â›Ó·È ÚÔÙÈÌfiÙÂÚÔ ¤Ó· ¯·Ï·Úfi ÙÚ¤ÍÈÌÔ ÌÈÛ‹˜ ÒÚ·˜ ·fi ¤Ó· ¤ÓÙÔÓÔ 15 ÏÂÙÒÓ).

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¶›Ó·Î·˜ 3. ∆·ÍÈÓfiÌËÛË ˘¤ÚÙ·ÛË˜ ÛÙ· ·ÁfiÚÈ· ·Ó¿ÏÔÁ· ÌÂ ÙÔ ‡„Ô˜ Î·È ÙËÓ ËÏÈÎ›· (·fi 1-10 ÂÙÒÓ) HÏÈÎ›· ∞¶ (¤ÙË) ∂Î·ÙÔÛÙÈ·›· ı¤ÛË

™˘ÛÙÔÏÈÎ‹ ∞¶ (mmHg) ∂Î·ÙÔÛÙÈ·›· ı¤ÛË ‡„Ô˘˜

¢È·ÛÙÔÏÈÎ‹ ∞¶ (mmHg) ∂Î·ÙÔÛÙÈ·›· ı¤ÛË ‡„Ô˘˜

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95 99

97 101

99 103

100 104

102 106

103 106

49 54

50 54

51 55

52 56

53 57

53 54 58 58

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97 101

99 102

100 104

102 106

104 108

105 109

106 110

54 59

55 59

56 60

57 61

58 62

58 59 63 63

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100 104

101 105

103 107

105 109

107 110

108 112

109 113

59 63

60 64

61 65

62 66

63 63 67 67

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102 106

103 107

105 109

107 111

109 112

110 114

111 115

62 66

63 67

64 68

65 69

66 70

66 67 71 71

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104 108

105 109

106 110

108 112

110 114

111 115

112 116

65 69

66 70

67 71

68 72

69 73

69 70 74 74

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105 109

106 110

108 112

110 114

111 115

113 117

68 72

69 73

70 74

71 75

72 72 76 76

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106 110

107 111

109 113

111 115

113 117

114 118

115 119

70 74

71 75

72 76

73 77

74 74 78 78

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107 111

109 112

110 114

112 116

114 118

115 119

116 120

71 75

72 76

72 77

73 78

74 79

75 76 79 80

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109 113

110 114

112 116

114 118

115 119

117 121

118 121

72 76

73 77

74 78

75 79

76 80

76 77 81 81

90‹ 95Ë

111 115

112 116

114 117

115 119

117 121

119 122

119 123

73 77

73 78

74 79

75 80

76 81

77 78 81 82

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113 117

114 118

115 119

117 121

119 123

120 124

121 125

74 78

75 79

76 80

77 81

78 78 82 82

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115 119

116 120

118 122

120 123

121 125

123 127

74 78

75 79

75 80

76 81

77 82

78 79 82 83

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117 121

118 122

120 124

122 126

124 128

125 129

126 130

75 79

76 80

77 81

78 82

79 79 83 83

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120 124

121 125

123 127

125 128

126 130

128 132

75 80

76 80

17 81

78 82

79 83

79 80 84 84

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122 126

124 127

125 129

127 131

129 133

130 134

131 135

76 81

77 81

78 82

79 83

80 84

80 81 85 85

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125 129

126 130

128 132

130 134

131 135

133 137

134 137

78 82

78 83

79 83

80 84

81 85

82 82 86 87

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127 131

128 132

130 134

132 136

134 138

135 139

136 140

80 84

80 85

81 86

82 87

83 87

84 84 88 89

™˘ÌÂÚ¿ÛÌ·Ù· Ÿˆ˜ Á›ÓÂÙ·È ·ÓÙÈÏËÙfi ·fi Ù· ÚÔ·Ó·ÊÂÚı¤ÓÙ· ÛÙÔÈ¯Â›·, Û¯Â‰fiÓ fiÏÔÈ ÔÈ ÓÂ·ÚÔ› ·ÛıÂÓÂ›˜ ÌÂ Û˘ÁÁÂÓ‹ ‹ Â›ÎÙËÙË Î·Ú‰ÈÔ¿ıÂÈ· ÌÔÚÔ‡Ó Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÂ Î¿ÔÈ· ·ıÏËÙÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ·, ¤ÛÙˆ Î·È ÔÏ‡ ‹È·. ¡· ÛËÌÂÈˆıÂ› fiÙÈ ÔÈ ÚÔ·Ó·ÊÂÚıÂ›ÛÂ˜ Ô‰ËÁ›Â˜ ·ÊÔÚÔ‡Ó ÙË Û˘ÌÌÂÙÔ¯‹ ÙÔ˘˜ ÛÂ ·ÓÙ·ÁˆÓÈÛÙÈÎ¿ ·ıÏ‹Ì·Ù· Î·È fiÙÈ

·ÎfiÌ· Î·È fiÙ·Ó Ë ÛÔ‚·ÚfiÙËÙ· ÙË˜ Î·Ù¿ÛÙ·ÛË˜ ÙÔ˘˜ ‰ÂÓ ÂÈÙÚ¤ÂÈ ÙÔÓ ·ÓÙ·ÁˆÓÈÛÙÈÎfi ·ıÏËÙÈÛÌfi, ÌÔÚÔ‡Ó Î·È Ú¤ÂÈ Ó· ‰È·ÙËÚÔ‡Ó Î¿ÔÈÔ˘ Â›‰Ô˘˜ Ê˘ÛÈÎ‹ ‰Ú·ÛÙËÚÈfiÙËÙ· „˘¯·ÁˆÁÈÎÔ‡ ¯·Ú·ÎÙ‹Ú·, ÂÈ‰ÈÎ¿ ˘fi ÙËÓ ÌÔÚÊ‹ Î¿ÔÈÔ˘ ÔÌ·‰ÈÎÔ‡ ·ıÏ‹Ì·ÙÔ˜, ÌÂ ÙËÓ ÚÔ¸fiıÂÛË ‚¤‚·È·, fiÙÈ ÙfiÛÔ Ô ·ÛıÂÓ‹˜ fiÛÔ Î·È Ô Î·ıËÁËÙ‹˜ ÛˆÌ·ÙÈÎ‹˜ ·ÁˆÁ‹˜ ¤¯Ô˘Ó Â›ÁÓˆÛË ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜ Î·È ÙˆÓ ÂÚÈÔÚÈÛÌÒÓ Ô˘ ÂÈ‚¿ÏÏÔÓÙ·È. Ÿˆ˜ Â›Ó·È ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

476

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100 104

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102 106

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52 56

53 57

54 58

55 59

55 56 59 60

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99 103

100 104

101 105

103 107

104 108

105 109

57 61

58 62

59 63

60 64

61 61 65 65

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102 105

103 107

104 108

106 109

106 110

61 65

62 66

63 67

64 68

64 65 68 69

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102 106

103 107

104 108

106 110

107 111

108 112

64 68

65 69

66 70

67 71

67 68 71 72

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105 108

106 110

107 111

109 112

109 113

66 70

67 71

68 72

69 73

69 70 73 74

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105 109

106 110

108 111

109 113

110 114

111 115

68 72

69 73

70 74

71 72 75 76

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107 111

108 112

109 113

111 115

112 116

113 116

69 73

70 74

71 75

72 76

72 73 76 77

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109 112

110 114

111 115

113 116

114 118

71 75

72 76

73 77

74 74 78 78

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112 115

113 117

114 118

j-.e 119

116 120

72 76

73 11

74 78

75 75 79 79

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114 117

115 119

116 120

118 121

118 122

73 77

74 78

75 79

76 76 80 80

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116 119

117 121

118 122

119 123

120 124

74 78

75 79

76 80

77 77 81 81

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116 119

116 120

117 121

119 123

120 124

121 125

122 126

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76 80

77 81

78 78 82 82

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117 121

118 122

119 123

121 124

122 126

123 127

124 128

76 80

77 81

78 82

79 79 S3 83

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120 123

121 125

122 126

124 127

125 129

77 81

78 82

79 83

80 80 84 84

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122 126

123 127

125 129

126 130

127 131

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79 83

80 84

81 81 85 85

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124 128

126 130

127 131

128 132

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81 85

81 82 85 86

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Â‡ÎÔÏ· ·ÓÙÈÏËÙfi, Ù· ÔÊ¤ÏË ·fi ÙËÓ „˘¯·ÁˆÁÈÎ‹ ·˘Ù‹ ÂÓ·Û¯fiÏËÛË Â›Ó·È ÔÏÏ·Ï¿, ÙfiÛÔ ÛÂ Â›Â‰Ô Ê˘ÛÈÎ‹˜ fiÛÔ Î·È „˘¯ÈÎ‹˜ ˘ÁÂ›·˜.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Maron BJ. Sudden death in young athletes. N Engl J Med 2003;349:1064-1075. ¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

¢È·ÛÙÔÏÈÎ‹ ∞¶ (mmHg) ∂Î·ÙÔÛÙÈ·›· ı¤ÛË ‡„Ô˘˜

2. Corrado D, Pelliccia A, Bjornstad HH, Vanhees L, Biffi A, Borjesson M et al. Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus Statement of the Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J 2005;26:516-524.

477

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3. Mitchell JH, Wildenthal K. Static (isometric) exercise and the heart: physiological and clinical considerations. Annu Rev Med 1974;25:369-381. 4. Asmussen E. Similarities and dissimilarities between static and dynamic exercise. Circ Res 1981;48:I3-10. 5. Blomqvist CG, Lewis SF, Taylor WF, Graham RM. Similarity of the hemodynamic responses to static and dynamic exercise of small muscle groups. Circ Res 1981;48:I-87-92. 6. Mitchell JH, Haskell W, Snell P, Van Camp SP. Task force 8: Classification of sports. J Am Coll Cardiol 2005;45:1364-1367. 7. Graham T Jr, Driscoll DJ, Gersony WM, Newburger JW, Rocchini A, Towbin JA. Task force 2: congenital heart disease.. J Am Coll Cardiol 2005;45:1326-1333. 8. Bonow RO, Cheitlin MD, Crawford MH, Douglas PS. Task force 3: valvular heart disease. J Am Coll Cardiol 2005;45:1334-1340. 9. Garson A Jr, Gillette PC, Gutgesell HP, McNamara DG. Stress-induced ventricular arrhythmia after repair of tetralogy of Fallot. Am J Cardiol 1980;46:1006-1012. 10. Elefteriades JA, Hatzaras I, Tranquilli MA, Elefteriades AJ, Stout R, Shaw RK et al. Weight lifting and rupture of silent aortic aneurysms. JAMA 2003;290:2803. 11. Maron BJ, Chaitman BR, Ackerman MJ, Bayes de Luna A, Corrado D, Crosson JE et al. Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases. Circulation 2004;109:2807-2816. 12. Maron BJ, Ackerman MJ, Nishimura RA, Pyeritz RE, Towbin JA, Udelson JE. Task force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol 2005;45:1340-1345. 13. Freed LA, Levy D, Levine RA, Larson MG, Evans JC, Fuller DL et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999;341:1-7. 14. Avierinos JF, Gersh BJ, Melton LJ 3rd, Bailey KR, Shub C, Nishimura RA et al. Natural history of asymptomatic mitral valve prolapse in the community. Circulation 2002;106:1355-1361. 15. Maron BJ, Shirani J, Mueller FO, Cantu RC, Roberts WC. Cardiovascular causes of "athletic field" deaths: analysis of sudden death in 84 competitive athletes. Circulation 1993;88 Suppl I:I-50. 16. Corrado D, Basso C, Nava A, Rossi L, Thiene G. Sudden death in young people with apparently isolated mitral valve prolapse. G Ital Cardiol 1997;27: 1097-1105.

17. Maron BJ. Hypertrophic cardiomyopathy: a systematic review. JAMA 2002;287:1308-1320. 18. Rosenzweig A, Watkins H, Hwang DS, Miri M, McKenna W, Traill TA et al. Preclinical diagnosis of familial hypertrophic cardiomyopathy by genetic analysis of blood lymphocytes. N Engl J Med 1991; 325:1753-1760. 19. Kaminer SJ, Hixon RL, Strong WB. Evaluation and recommendations for participation in athletics for children with heart disease. Curr Opin Pediatr 1995;7:595-600. 20. Paridon SM, Ross RD, Kuhns LR, Pinsky WW. Myocardial performance and perfusion during exercise in patients with coronary artery disease caused by Kawasaki disease. J Pediatr 1990;116:52-56. 21. °ÂˆÚÁ·ÎfiÔ˘ÏÔ˜ ¢, ª·ÚÁÂÙ¿ÎË˜ ∞. ¡ÂÒÙÂÚ· ‰Â‰ÔÌ¤Ó· ÁÈ· ÙÈ˜ Ì·ÎÚÔÚfiıÂÛÌÂ˜ Û˘Ó¤ÂÈÂ˜ ÙË˜ ÓfiÛÔ˘ Kawasaki. ¶·È‰È·ÙÚÈÎ‹ 1998;61:360-362. 22. Zipes DP, Ackerman MJ, Estes NA 3rd, Grant AO, Myerburg RJ, Van Hare G. Task force 7: Arrhythmias. J Am Coll Cardiol 2005;45:1354-1363. 23. Furlanello F, Bertoldi A, Bettini R, Dallago M, Vergara G. Life-threatening tachyarrhythmias in athletes. Pacing Clin Electrophysiol 1992;15:1403-1411. 24. Munger TM, Packer DL, Hammill SC, Feldman BJ, Bailey KR, Ballard DJ et al. A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989. Circulation 1993;87:866-73. 25. Ackerman MJ. The long QT syndrome: ion channel diseases of the heart. Mayo Clin Proc 1998;73:250-69. 26. Bjornstad H, Storstein L, Meen HD, Hals O. Ambulatory electrocardiographic findings in top athletes, athletic students and control subjects. Cardiology 1994;84:42-50. 27. Update on the 1987 task force report on high blood pressure in children and adolescents: a working group report from the national high blood pressure education program. National High Blood Pressure Education Program Working on Hypertension Control in Children and Adolescents. Pediatrics 1996;98:649-58. 28. Barlow SE, Dietz WH. Obesity evaluation and treatment: expert committee recommendations. The Maternal and Child Health Bureau, Health Resources and Services Administration and the Department of Health and Human Services. Pediatrics 1998;102:1-11.

¶·È‰È·ÙÚÈÎ‹ 2006;69:468-477

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∫oÚ›ÙÛÈ 8,5 ÂÙÒÓ ÂÈÛ‹¯ıË ÌÂ ·‰˘Ó·Ì›· ‚¿‰ÈÛË˜ Î·È ÔÚıÔÎ˘ÛÙÈÎ¤˜ ‰È·Ù·Ú·¯¤˜ ·fi 12ÒÚÔ˘, Î·ıÒ˜ Î·È Ì˘·ÏÁ›· Î·È ¿ÏÁÔ˜ ÛÙËÓ ÔÛÊ‡ ·fi 48ÒÚÔ˘. ¶ÚÔ ÂÓıËÌ¤ÚÔ˘ ·ÚÔ˘Û›·ÛÂ ÂÌ‡ÚÂÙÔ Û˘ÓÔ‰Â˘fiÌÂÓÔ ·fi ‚‹¯· Î·È ÎÂÊ·Ï·ÏÁ›·, Ô˘ ‰È‹ÚÎÂÛ·Ó 36 ÒÚÂ˜. ∞fi ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈÎ‹ ÂÍ¤Ù·ÛË Î·Ù¿ ÙËÓ ÂÈÛ·ÁˆÁ‹, ‰È·ÈÛÙÒıËÎÂ Ì˘˚Î‹ ·‰˘Ó·Ì›· ÛÙ· Î¿Ùˆ ¿ÎÚ· Î·È ‰˘ÛÎÔÏ›· ÔÚıÔÛÙ¿ÙËÛË˜. ∆· ÙÂÓfiÓÙÈ· ·ÓÙ·Ó·ÎÏ·ÛÙÈÎ¿ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎ¿. ∏ Î·Ù¿ Û˘ÛÙ‹Ì·Ù· ÂÍ¤Ù·ÛË ‹Ù·Ó ÂÓÙfi˜ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÔÚ›ˆÓ. ∞fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ÚÔ¤Î˘„·Ó Ù· ·Ú·Î¿Ùˆ: ÁÂÓÈÎ‹ ·›Ì·ÙÔ˜ Î·È ·‰Úfi˜ ‚ÈÔ¯ËÌÈÎfi˜ ¤ÏÂÁ¯Ô˜: Î.Ê., ÁÂÓÈÎ‹ ∂¡À (ÙËÓ 5Ë ËÌ¤Ú· ·fi ÙËÓ ¤Ó·ÚÍË ÙË˜ ÓfiÛÔ˘): Î‡ÙÙ·Ú· 240 (Ù‡Ô˜ ÏÂÌÊÔÎ˘ÙÙ·ÚÈÎfi˜), ÏÂ‡ÎˆÌ· 30 mg/dl, Û¿Î¯·ÚÔ 49 mg/dl, ¿ÌÂÛÔ (-). ∆· ·ÓÙÈÛÒÌ·Ù· ÛÙÔ ∂¡À ÁÈ· ·‰ÂÓÔ˚Ô‡˜, ÂÚËÙo˚o‡˜, ÂÓÙÂÚo˚o‡˜, ÁÚ›Ë, ·Ú·ÁÚ›Ë, CMV Î·È EBV ‹Ù·Ó fiÏ· ·ÚÓËÙÈÎ¿. ∏ PCR ÛÙÔ ∂¡À ÁÈ· µorellia burgdorferi Î·È HSV1 Î·È HSV2 ‹Ù·Ó Â›ÛË˜ ·ÚÓËÙÈÎ‹. ∞fi ÙÔÓ ÔÚÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ÚÔ¤Î˘„·Ó Ù· ·Ú·Î¿Ùˆ: C3: 194 mg/dl (º∆ 52120), C4: 36 mg/dl, ASTO (-), ANA 1:160, anti DNA: (-), ÂÓÒ ÔÈ IgG, IgA Î·È IgM ‹Ù·Ó ÂÓÙfi˜ Ê˘-

ÛÈÔÏÔÁÈÎÒÓ ÔÚ›ˆÓ Î·È Ù· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ENA, RNP, Sm, SSA Î·È SSB fiÏ· ·ÚÓËÙÈÎ¿. ∆· ·ÓÙÈÛÒÌ·Ù· ÛÙÔÓ ÔÚfi ÁÈ· ¯Ï·Ì‡‰È·, HSV, CMV, EBV, Toxoplasma, Bartonella, Influenza A, B, ·‰ÂÓÔ˚Ô‡˜, ÂÓÙÂÚÔ˚Ô‡˜ ‹Ù·Ó fiÏ· ·ÚÓËÙÈÎ¿, ÂÓÒ, fiÛÔÓ ·ÊÔÚ¿ Ù· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ Ì˘ÎÔÏ¿ÛÌ·ÙÔ˜ ÙË˜ ÓÂ˘ÌÔÓ›·˜, ‚Ú¤ıËÎ·Ó ¤ÓÙÔÓ· ıÂÙÈÎ¿ Ù· IgM Î·È ·ÛıÂÓÒ˜ ıÂÙÈÎ¿ Ù· IgG. √ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ∂¡À ÁÈ· ÔÏÈÁÔÎÏˆÓÈÎ¿ ·ÓÙÈÛÒÌ·Ù· ‹Ù·Ó ·ÚÓËÙÈÎfi˜. ∏ Ù·¯‡ÙËÙ· ·ÁˆÁ‹˜ ÓÂ‡ÚˆÓ ‹Ù·Ó ÂÓÙfi˜ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÔÚ›ˆÓ. ∏ Ì·ÁÓËÙÈÎ‹ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎ‹, ÂÓÒ ÙË˜ ıˆÚ·ÎÈÎ‹˜ Î·È ÙË˜ ÔÛÊ˘˚Î‹˜ ÌÔ›Ú·˜ ÙË˜ ÛÔÓ‰˘ÏÈÎ‹˜ ÛÙ‹ÏË˜ ¤‰ÂÈÍÂ ÂÏ·ÊÚ¿ ‰ÈfiÁÎˆÛË ÙÔ˘ Ì˘ÂÏÈÎÔ‡ ÛˆÏ‹Ó· ÛÙËÓ ·ÓÒÙÂÚË ıˆÚ·ÎÈÎ‹ Î·È ÛÙËÓ Î·ÙÒÙÂÚË ·˘¯ÂÓÈÎ‹ ÌÔ›Ú· Ù‹˜ ÛÔÓ‰˘ÏÈÎ‹˜ ÛÙ‹ÏË˜ Î·ıÒ˜ Î·È ·˘ÍËÌ¤ÓÔ Û‹Ì· ÛÙËÓ ∆2 ·ÎÔÏÔ˘ı›· (∂ÈÎfiÓ· 1).

1 ∞’ ¶·È‰È·ÙÚÈÎ‹ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” 2 ¡Â˘ÚÔÏÔÁÈÎﬁ ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” AÏÏËÏÔÁÚ·Ê›·: ∞ÏÂÍ¿Ó‰Ú· ¶··‰ÔÔ‡ÏÔ˘ E-mail: papadop6@otenet.gr

¶Èı·Ó¤˜ ‰È·ÁÓÒÛÂÈ˜: 1. Guillain Barré 2. ™ÎÏ‹Ú˘ÓÛË Î·Ù¿ Ï¿Î·˜ 3. ∂ÁÎ¿ÚÛÈ· Ì˘ÂÏ›ÙÈ‰· 4. ™˘ÛÙËÌ·ÙÈÎﬁ˜ ÂÚ˘ıËÌ·ÙÒ‰Ë˜ Ï‡ÎÔ˜

∏ ·¿ÓÙËÛË ·ÎÔÏÔ˘ıÂ› ÛÙË ÛÂÏ›‰· 482 ¶·È‰È·ÙÚÈÎ‹ 2006;69:479,482

480

µ’ ¶·È‰È·ÙÚÈÎ‹ ¶·ÓÂÈÛÙËÌÈ·Î‹ ∫ÏÈÓÈÎ‹, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ¡›ÎÔ˜ ¶··‰ﬁÔ˘ÏÔ˜ E-mail: ngp@allergy.gr

¡∂∞ ∞¶√ ∆√ ¢π∞¢π∫∆À√

¡›ÎÔ˜ ¶··‰ﬁÔ˘ÏÔ˜, ¶·È‰›·ÙÚÔ˜, ∞ÏÏÂÚÁÈÔÏﬁÁÔ˜

™‡Á¯ÚÔÓ· ËÏÂÎÙÚÔÓÈÎ¿ ÓËÈ·ÁˆÁÂ›· ∞˘Ùfi ÙÔ Ì‹Ó·, Ë ÛÙ‹ÏË ·ÚÔ˘ÛÈ¿˙ÂÈ ÂÈ‰ÈÎfi ·ÊÈ¤ÚˆÌ· ÛÙÔ˘˜ ‰ÈÎÙ˘·ÎÔ‡˜ ÙfiÔ˘˜ ÌÂ ÂÎ·È‰Â˘ÙÈÎfi Î·È ÂÓËÌÂÚˆÙÈÎfi ÂÚÈÂ¯fiÌÂÓÔ Û¯ÂÙÈÎ¿ ÌÂ ÙËÓ ÔÚı‹ ¯Ú‹ÛË ÙÔ˘ ¢È·‰ÈÎÙ‡Ô˘ ·fi Ù· ·È‰È¿ Î·È ÙÔ˘˜ ÁÔÓÂ›˜. ∫·Ï‹ ÏÔ‹ÁËÛË!

¶·›˙ˆ Î·È Ì·ı·›Óˆ ·fi ÙÔ ÿÓÙÂÚÓÂÙ! – http://pbskids.org/ √ ‰ÈÎÙ˘·Îfi˜ ÙfiÔ˜ pbskids.org ·Ó‹ÎÂÈ ÛÙÔÓ ·ÌÂÚÈÎ·ÓÈÎfi Ú·‰ÈÔÙËÏÂÔÙÈÎfi ÊÔÚ¤· ‰ËÌÔÛ›Ô˘ Û˘ÌÊ¤ÚÔÓÙÔ˜, Public Broadcasting Service (PBS) Î·È ¤¯ÂÈ ˆ˜ Â›ÎÂÓÙÚÔ ÙËÓ ËÏÂÎÙÚÔÓÈÎ‹ ‰È··È‰·ÁÒÁËÛË ÙˆÓ ·È‰ÈÒÓ, ÙˆÓ ÁÔÓ¤ˆÓ Î·È ÙˆÓ ‰·ÛÎ¿ÏˆÓ ÁÈ· ÙËÓ ÚÔÛÙ·Û›· Î·È ÙË ıˆÚ¿ÎÈÛ‹ ÙÔ˘˜ ·¤Ó·ÓÙÈ ÛÙ· Ó¤· ª¤Û· ∂ÈÎÔÈÓˆÓ›·˜, Î·È ÂÈ‰ÈÎfiÙÂÚ· ÛÙÔ ¢È·‰›ÎÙ˘Ô. ∞ÒÙÂÚÔ˜ ÛÙfi¯Ô˜ Â›Ó·È Ë Î·Ù·Ú¯¿˜ ıÂÙÈÎ‹ ÚÔÛ¤ÁÁÈÛË ·¤Ó·ÓÙÈ ÛÙÔ ÿÓÙÂÚÓÂÙ Î·È Ë ÂÍÔÈÎÂ›ˆÛ‹ ÙÔ˘˜ ÌÂ ÙÔ Ó¤Ô ·˘Ùfi Ì¤ÛÔ ÁÈ· „˘¯·ÁˆÁÈÎÔ‡˜ Î·È ÂÎ·È‰Â˘ÙÈÎÔ‡˜ ÛÎÔÔ‡˜, ‰ËÌÈÔ˘ÚÁÒÓÙ·˜ ¤Ó· ÂÓ ‰˘Ó¿ÌÂÈ “ËÏÂÎÙÚÔÓÈÎfi ÓËÈ·ÁˆÁÂ›Ô”. ∏ ÎÂÓÙÚÈÎ‹ ÛÂÏ›‰· (Homepage) Â›Ó·È ÂÓÙ˘ˆÛÈ·Î‹ ÌÂ ÔÏÏ¿ ¯ÚÒÌ·Ù·, ‹¯Ô˘˜ Î·È ÔÏÏ¤˜ ‰È·‰Ú·ÛÙÈÎ¤˜ ÏÂÈÙÔ˘ÚÁ›Â˜ ·Ú·¤ÌÔÓÙ·˜ ÛÂ ·È¯Ó›‰È· ÚÔÛ¯ÔÏÈÎ‹˜ ËÏÈÎ›·˜. √È ‚·ÛÈÎ¤˜ Î·ÙËÁÔÚ›Â˜, Â›Ó·È ÙÚÂÈ˜, PBS °È· ¢·ÛÎ¿ÏÔ˘˜, PBS °È· ¶·È‰È¿ Î·È PBS °È· °ÔÓÂ›˜, Ë Î·ıÂÌ›· ÌÂ ·ÓÙ›ÛÙÔÈ¯Ô ÂÚÈÂ¯fiÌÂÓÔ Î·È ‰È·ÊÔÚÂÙÈÎfi Û¯Â‰È·ÛÌfi. √È 3 ·˘Ù¤˜ Î·ÙËÁÔÚ›Â˜ ÏÂÈÙÔ˘ÚÁÔ‡Ó Ù·˘Ùfi¯ÚÔÓ· Î·È ˆ˜ ‰ÈÎÙ˘·Î¤˜ ‡ÏÂ˜ ÁÈ· ÙfiÔ˘˜ ÌÂ ·ÚÂÌÊÂÚ¤˜ ÂÚÈÂ¯fiÌÂÓÔ. π‰È·›ÙÂÚÔ ÂÓ‰È·Ê¤ÚÔÓ ·ÚÔ˘ÛÈ¿˙ÂÈ Ë Î·ÙËÁÔÚ›· PBS °È· ¶·È‰È¿, Ë ÔÔ›· ·Â˘ı‡ÓÂÙ·È ÛÂ ÌÈÎÚ¤˜ ËÏÈÎ›Â˜ Î·È ÂÚÈÏ·Ì‚¿ÓÂÈ ·È¯Ó›‰È·, ‰È·ÁˆÓÈÛÌÔ‡˜, ˙ˆÁÚ·ÊÈÎ‹ ÎÈÓÔ˘Ì¤ÓˆÓ Û¯Â‰›ˆÓ ·ÏÏ¿ Î·È ·Ú·Ì‡ıÈ·, Ù· ÔÔ›· ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÛÂ ‰È·‰Ú·ÛÙÈÎ‹ ÌÔÚÊ‹. ∆· ·È‰È¿-¯Ú‹ÛÙÂ˜ ¤¯Ô˘Ó Â›ÛË˜ ÙË ‰˘Ó·ÙfiÙËÙ·, Ó· ·ÎÔ‡ÛÔ˘Ó ÌÔ˘ÛÈÎ¿ ÎÔÌÌ¿ÙÈ· Î·È ÛÙË Û˘Ó¤¯ÂÈ· Ó· Û˘Óı¤ÛÔ˘Ó Ù· ›‰È· ÙË ÌÔ˘ÛÈÎ‹ Ô˘ ¿ÎÔ˘Û·Ó, ‹ ÔÔÈ·‰‹ÔÙÂ ¿ÏÏË ÌÔ˘ÛÈÎ‹ Û‡ÓıÂÛË ÂÈı˘ÌÔ‡Ó. ∏ Î·ÙËÁÔÚ›· PBS °È· °ÔÓÂ›˜ ÂÚÈÏ·Ì‚¿ÓÂÈ ÏËÚÔÊÔÚ›Â˜ Î·È Û˘Ì‚Ô˘Ï¤˜ Û¯ÂÙÈÎ¿ ÌÂ ÙËÓ „˘¯ÔÛˆÌ·ÙÈÎ‹ ·Ó¿Ù˘ÍË Î·È Û˘ÌÂÚÈÊÔÚ¿ ÙˆÓ ·È‰ÈÒÓ Î·ıÒ˜ Î·È Ô‰ËÁ›Â˜ ÁÈ· ÌÈ· ·ÔÙÂÏÂÛÌ·ÙÈÎ‹ ÂÈÎÔÈÓˆÓÈ·Î‹ ÚÔÛ¤ÁÁÈÛË, Ï·Ì‚¿ÓÔÓÙ·˜ ˘fi„ÈÓ ÙÔÓ Â˘·›ÛıËÙÔ „˘¯ÈÎfi ÙÔ˘˜ ÎfiÛÌÔ. ∆¤ÏÔ˜, ÛÙËÓ Î·ÙËÁÔÚ›· PBS °È· ¢·ÛÎ¿ÏÔ˘˜ Â›Ó·È ‰È·ı¤ÛÈÌÔ˜ Ô‰ËÁfi˜ ÌÂ ‚·ÛÈÎ¤˜ Ô‰ËÁ›Â˜ Î·È Ú·ÎÙÈÎ¤˜ Î·Ï‹˜ ‰È‰·ÛÎ·Ï›·˜ ÛÙÔ Û¯ÔÏÂ›Ô. √ ‰ÈÎÙ˘·Îfi˜ ÙfiÔ˜ pbskids.org ¤¯ÂÈ ‰ËÌÈÔ˘ÚÁ‹ÛÂÈ Â›ÛË˜ Î·È Ì›· ı˘Á·ÙÚÈÎ‹ ÈÛÙÔÛÂÏ›‰· http://pbskids.org/dontbuyit, Ë ÔÔ›· ·Â˘ı‡ÓÂÙ·È ÛÙÔ˘˜ ÁÔÓÂ›˜, ‰·ÛÎ¿ÏÔ˘˜ Î·È ·È‰È¿ - Î·Ù·Ó·ÏˆÙ¤˜ ÌÂ ÛÙfi¯Ô ÙËÓ ÂÓÂÚÁËÙÈÎ‹ ÚÔÛÙ·Û›· ÙÔ˘˜ ·fi ÙËÓ ÏËıÒÚ· ÚÔ˚fiÓÙˆÓ ÛÙÔ ¢È·‰›ÎÙ˘Ô.

¶·È‰È·ÙÚÈÎ‹ 2006;69:480-481

NEWS FROM THE INTERNET

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∂ÈÎÔÈÓˆÓ›· …Î·È Â˘·ÈÛıËÛ›·! - http://www.media-awareness.ca/ ∏ ÈÛÙÔÛÂÏ›‰· http://www.media-awareness.ca ·ÔÙÂÏÂ› ÙÔÓ Â›ÛËÌÔ ‰ÈÎÙ˘·Îfi ÙfiÔ ÙÔ˘ Media Awareness Network, ÂÓfi˜ ÌËÎÂÚ‰ÔÛÎÔÈÎÔ‡ ÔÚÁ·ÓÈÛÌÔ‡ Ô˘ Â‰ÚÂ‡ÂÈ ÛÙÔÓ ∫·Ó·‰¿ Î·È ¤¯ÂÈ ˆ˜ ·ÓÙÈÎÂ›ÌÂÓÔ ÙËÓ Â˘·ÈÛıËÙÔÔ›ËÛË ÙˆÓ ÁÔÓ¤ˆÓ Î·È ÙˆÓ ‰·ÛÎ¿ÏˆÓ ÛÙË ¯Ú‹ÛË ÙˆÓ Ó¤ˆÓ ÙÂ¯ÓÔÏÔÁÈÒÓ. ™Ùfi¯Ô˜ Â›Ó·È Ë Î·Ù¿ÚÙÈÛË Î·È Ë ÂÓËÌ¤ÚˆÛË Û¯ÂÙÈÎ¿ ÌÂ ÙÈ˜ ‚·ÛÈÎ¤˜ ÏÂÈÙÔ˘ÚÁ›Â˜ ÙˆÓ Ó¤ˆÓ ª¤ÛˆÓ ∂ÈÎÔÈÓˆÓ›·˜ ÁÈ· ÙËÓ ·fiÎÙËÛË ÙË˜ ··ÈÙÔ‡ÌÂÓË˜ ÎÚÈÙÈÎ‹˜ ÛÎ¤„Ë˜ Î·È ÙË˜ Î·Ù¿ Û˘Ó¤ÂÈ· ÔÚı‹˜ Î·Ù·Ó·ÏˆÙÈÎ‹˜ Û˘ÌÂÚÈÊÔÚ¿˜. ∞˘Ùfi ÙÔ ÂÙ˘¯·›ÓÂÈ Ì¤Û· ·fi ÂÈ‰ÈÎ¿ Û¯Â‰È·ÛÌ¤Ó· ÚÔÁÚ¿ÌÌ·Ù·, ·fi Ù· ÔÔ›· ÍÂ¯ˆÚ›˙ÂÈ ÙÔ ÚfiÁÚ·ÌÌ· Web Awareness Canada, Ô˘ ÍÂÎ›ÓËÛÂ ÙÔ 1999 Î·È Û˘ÓÂ¯›˙ÂÙ·È Ì¤¯ÚÈ Û‹ÌÂÚ·. √ ‰ÈÎÙ˘·Îfi˜ ÙfiÔ˜ ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ·ÔÙÂÏÂ› ¤Ó· Ì¤ÛÔ ÚÔ‚ÔÏ‹˜ ÙË˜ Û˘ÓÔÏÈÎ‹˜ ‰Ú¿ÛË˜ Î·È ÙˆÓ ÂÈÌ¤ÚÔ˘˜ ÚˆÙÔ‚Ô˘ÏÈÒÓ ÙÔ˘. §ÂÈÙÔ˘ÚÁÂ› Â›ÛË˜, Î·È ˆ˜ ËÁ‹ ÏËÚÔÊÔÚÈÒÓ Ì¤Û· ·fi blogs, forums ¿Óˆ ÛÂ ı¤Ì·Ù· Î·›ÚÈ·˜ ÛËÌ·Û›·˜ ÁÈ· ÁÔÓÂ›˜ Î·È ‰·ÛÎ¿ÏÔ˘˜, fiˆ˜ Ë ·Ó··Ú¿ÛÙ·ÛË ÙË˜ ‚›·˜, Ù· ÛÙÂÚÂfiÙ˘· Ì¤Û· ·fi Ù· ªª∂ Î.¿. ∂Ó‰È·Ê¤ÚÔÓ ·ÚÔ˘ÛÈ¿˙ÂÈ Ô ËÏÂÎÙÚÔÓÈÎfi˜ Î·Ù¿ÏÔÁÔ˜ ÌÂ ÔÙÈÎÔ·Ô˘ÛÙÈÎfi ˘ÏÈÎfi ÁÈ· ÚÔÛˆÈÎ‹ ·ÏÏ¿ Î·È Â·ÁÁÂÏÌ·ÙÈÎ‹ ¯Ú‹ÛË, ÌÂ Ô‰ËÁ›Â˜ Î·È ÚÔÙ¿ÛÂÈ˜ ÛˆÛÙ‹˜ ‰È··È‰·ÁÒÁËÛË˜ ÛÙ· ¡¤· ª¤Û·. ∏ ÈÛÙÔÛÂÏ›‰· Â›Ó·È ‰›ÁÏˆÛÛË, ÛÙ· ∞ÁÁÏÈÎ¿ Î·È Ù· °·ÏÏÈÎ¿, ÂÓÒ ÂÎÙfi˜ ·fi ÙË ÁÂÓÈÎ‹ ‰ÔÌ‹, ÂÚÈÏ·Ì‚¿ÓÂÈ Î·È ÍÂ¯ˆÚÈÛÙ¤˜ ÂÓfiÙËÙÂ˜ ÚÔ˜ ÁÔÓÂ›˜ Î·È ‰·ÛÎ¿ÏÔ˘˜.

Childnet International - http://www.childnet-int.org ™Ùfi¯Ô˜ ÙÔ˘ Childnet International Â›Ó·È Ë ‰ËÌÈÔ˘ÚÁ›· ÂÓfi˜ ·ÛÊ·Ï¤ÛÙÂÚÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ ÁÈ· Ù· ·È‰È¿ ÛÙÔ ÿÓÙÂÚÓÂÙ. ¶ÚfiÎÂÈÙ·È ÁÈ· ¤Ó·Ó ÔÚÁ·ÓÈÛÌfi ÌË-ÎÂÚ‰ÔÛÎÔÈÎÔ‡ ¯·Ú·ÎÙ‹Ú· Ô ÔÔ›Ô˜, Ì¤Û· ·fi ¤Ó· ‰ÈÂıÓ¤˜ ‰›ÎÙ˘Ô Û˘ÓÂÚÁ·ÛÈÒÓ, ÂÈ¯ÂÈÚÂ› ÌÈ· ÈÛÔÚÚÔËÌ¤ÓË ÚÔÛ¤ÁÁÈÛË ÛÙÔÓ ¯ÒÚÔ ÙÔ˘ ÿÓÙÂÚÓÂÙ ÌÂ 3 ‚·ÛÈÎÔ‡˜ ¿ÍÔÓÂ˜ ÂÓËÌ¤ÚˆÛË˜: ÚfiÛ‚·ÛË Î·È ÚÔÒıËÛË ÔÈÔÙÈÎÔ‡ ÂÚÈÂ¯ÔÌ¤ÓÔ˘, ∂˘·ÈÛıËÙÔÔ›ËÛË Î·È ¶ÚÔÛÙ·Û›·. ™ÙÔ Ï·›ÛÈÔ ·˘Ùfi, Ë ÈÛÙÔÛÂÏ›‰· childnet-int.org ÏÂÈÙÔ˘ÚÁÂ› ˆ˜ ÂÓËÌÂÚˆÙÈÎfi˜ ÎfiÌ‚Ô˜ ÙˆÓ ‰Ú·ÛÙËÚÈÔÙ‹ÙˆÓ ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÌÂ ‚·ÛÈÎÔ‡˜ ·Ô‰¤ÎÙÂ˜ ÁÔÓÂ›˜ Î·È ·È‰È¿. ∞Ó¿ÌÂÛ· ÛÙ· ¤ÚÁ·-‰Ú¿ÛÂÈ˜ ÌÂ ÛÙfi¯Ô ÙË ‰È··È‰·ÁÒÁËÛË Î·È ÙËÓ „˘¯·ÁˆÁ›· Â›Ó·È Î·È ÙÔ Kidsmart Ô˘ ·ÔÙÂÏÂ› ¤Ó· ·˘ÙfiÓÔÌÔ ÛÙËÓ Ô˘Û›· ‰ÈÎÙ˘·Îfi ÙfiÔ ÌÂ ÂÍ·ÙÔÌÈÎÂ˘Ì¤ÓÔ ÂÚÈÂ¯fiÌÂÓÔ ÁÈ· ·È‰È¿ (·È¯Ó›‰È·, chats, quiz, test ÁÓÒÛÂˆÓ), ÁÈ· ‰·ÛÎ¿ÏÔ˘˜ ÁÈ· ÙËÓ ÂÈÌfiÚÊˆÛË Û¯ÂÙÈÎ¿ ÌÂ ÙËÓ ·ÛÊ·Ï‹ ¯Ú‹ÛË ÙÔ˘ ÿÓÙÂÚÓÂÙ ÛÙÔ Û¯ÔÏÂ›Ô Î·È ÁÈ· ÁÔÓÂ›˜/Â·ÁÁÂÏÌ·Ù›Â˜ ÌÂ Ú·ÎÙÈÎ¤˜ Ô‰ËÁ›Â˜ Î·È ÂÓËÌÂÚˆÙÈÎfi ˘ÏÈÎfi. ÕÏÏ· ÚÔÁÚ¿ÌÌ·Ù· ÙÔ˘ Childnet International Â›Ó·È ÙÔ Parent’s support, Blog safety, Know it All, Young people music & the Internet, Childnet Academy. √ Û¯Â‰È·ÛÌfi˜ ÙË˜ ÈÛÙÔÛÂÏ›‰·˜ Â›Ó·È ·ÚÎÂÙ¿ ÌÔÓÙ¤ÚÓÔ˜ ÌÂ ÏÔ‡ÛÈÔ ÂÓËÌÂÚˆÙÈÎfi ˘ÏÈÎfi ÛÙËÓ ÚÒÙË ÛÂÏ›‰· Î·È ÌÈ· “¤Í˘ÓË” ÂÓ·ÏÏ·Á‹ ÊˆÙÔÁÚ·ÊÈÒÓ Ì¤Û· ·fi ÙÔ ÎÂÓÙÚÈÎfi flash.

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CLINICAL QUIZ ∫ÏÈÓÈÎﬁ QUIZ ∞¶∞¡∆∏™∏

∂ÁÎ¿ÚÛÈ· Ì˘ÂÏ›ÙÈ‰· ∏ ÂÁÎ¿ÚÛÈ· Ì˘ÂÏ›ÙÈ‰· ÂÌÊ·Ó›˙ÂÙ·È Î˘Ú›ˆ˜ ÛÂ ·È‰È¿ ÚoÂÊË‚ÈÎ‹˜ ËÏÈÎ›·˜, Î·È Û·ÓÈfiÙ·Ù· ÛÂ Ó‹È·. ™ÙÔ 70% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ë ÓfiÛo˜ ÂÎ‰ËÏÒÓÂÙ·È ÌÂÙ¿ ·fi Ïo›ÌˆÍË, 7-14 Ì¤ÚÂ˜ ·fi ÙËÓ ¤Ó·ÚÍË ÙË˜ ÓfiÛo˘. OÈ ÏoÈÌoÁfiÓoÈ ·Ú¿ÁoÓÙÂ˜ o˘ ¤¯o˘Ó ÂÓo¯ooÈËıÂ› Ì¤¯ÚÈ Û‹ÌÂÚ· Â›Ó·È oÈ Èo› ÙË˜ ÈÏ·Ú¿˜, ÙË˜ ·ÓÂÌÂ˘ÏoÁÈ¿˜, ÙË˜ ·ÚˆÙ›ÙÈ‰·˜, ÙË˜ ÁÚ›Ë˜, EBV, CMV, HSV1,2, HIV, Coxsackie, Ë·Ù›ÙÈ‰·˜ ∞ Î·È µ, Î·ıÒ˜ Î·È Ù· ÌÈÎÚfi‚È· ·ÈÌoÏ˘ÙÈÎfi˜ ÛÙÚÂÙfiÎoÎÎo˜ · Î·È ‚, Campylobacter, Salmonella, Chlamydia, Mycoplasma, Legionella, Leptospirosis, Borrelia burgdorferi Î·È Rickettsia. ™ÙËÓ ÂÚÈÁÚ·ÊÂ›Û· ÂÚ›ÙˆÛË ÚÔËÁ‹ıËÎÂ ÏÔ›ÌˆÍË ·fi Ì˘ÎfiÏ·ÛÌ·. ™Â fi,ÙÈ ·ÊÔÚ¿ ÛÙËÓ ·ıoÁ¤ÓÂÈ· ÙË˜ ÓfiÛÔ˘, ÈÛÙÂ‡ÂÙ·È fiÙÈ ÔÊÂ›ÏÂÙ·È ÛÂ ·˘Ùo¿ÓoÛË ‰ÈÂÚÁ·Û›· Ë ÔÔ›· ˘ÚÔ‰ÔÙÂ›Ù·È ·fi ÏoÈÌoÁfiÓo ÌÈÎÚooÚÁ·ÓÈÛÌfi Ì¤Ûˆ Ùo˘ Ê·ÈÓoÌ¤Óo˘ ÙË˜ “ÌoÚÈ·Î‹˜ ·oÌ›ÌËÛË˜” (molecular mimicry). ∫·Ù¿ Ùo Ê·ÈÓfiÌÂÓo ·˘Ùfi, ÚˆÙÂ˚ÓÈÎ¿ ÂÙ›‰È· Ùo˘ ·ıoÁfiÓo˘ ÌÈÎÚooÚÁ·ÓÈÛÌo‡, Ù· ÔÔ›· ¤¯Ô˘Ó ·ÚfiÌÔÈ· ‰ÔÌ‹ ÌÂ Ù· ÂÙ›‰È· ÙË˜ ‚·ÛÈÎ‹˜ ÚˆÙÂ˝ÓË˜ ÙË˜ Ì˘ÂÏ›ÓË˜, ÙË˜ ÚˆÙÂoÏÈÈ‰ÈÎ‹˜ ÚˆÙÂ˝ÓË˜ Î·È ÙË˜ Ì˘ÂÏÈÓooÏÈÁo‰ÂÓ‰ÚÈÙÈÎ‹˜ ÁÏ˘ÎoÚˆÙÂ˝ÓË˜ Ùo˘ ·ÛıÂÓÔ‡˜, ÂÓÂÚÁÔÔÈÔ‡Ó Ù· ∆-ÏÂÌÊoÎ‡ÙÙ·Ú· ÛÙo ∫¡™ ÂÓ¿ÓÙÈ· ÛÙÈ˜ Û˘ÁÎÂÎÚÈÌ¤ÓÂ˜ ÚˆÙÂ˝ÓÂ˜ ÙÔ˘ ·ÛıÂÓÔ‡˜. ¢È·ÊÔÚÈÎ‹ ‰È¿ÁÓˆÛË Ú¤ÂÈ Ó· Á›ÓÂÙ·È ·fi ÙÔ ÚÒÙÔ ÂÂÈÛfi‰ÈÔ ÙË˜ ÛÎÏ‹Ú˘ÓÛË˜ Î·Ù¿ Ï¿Î·˜, ÙË ÓfiÛÔ Guillain Barré, ÙË Û˘Ì›ÂÛË ·fi fiÁÎÔ Î·È ¿ÏÏ· Û˘ÛÙËÌ·ÙÈÎ¿ ÓÔÛ‹Ì·Ù· °È· ÙË ıÂÚ·Â›· ÙË˜ ÓfiÛÔ˘ ¯ÚËÛÈÌooÈo‡ÓÙ·È Ù· ÎoÚÙÈÎoÛÙÂÚoÂÈ‰‹ ÛÂ ˘„ËÏ¤˜ ‰fiÛÂÈ˜ ¯ÔÚËÁÔ‡ÌÂÓ· ÂÓ‰oÊÏÂ‚›ˆ˜, ‰ÈfiÙÈ ÈÛÙÂ‡ÂÙ·È fiÙÈ ÌÂÈÒÓo˘Ó ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÓÂ˘ÚoÏoÁÈÎÒÓ Û˘ÌÙˆÌ¿ÙˆÓ. ™˘Ó‹ıˆ˜ ¯oÚËÁÂ›Ù·È ÌÂı˘ÏÚÂ‰ÓÈ˙oÏfiÓË ÛÂ ‰fiÛË 20-30 mg/kgµ™/ËÌÂÚËÛ›ˆ˜ ÁÈ· 3-5 ËÌ¤ÚÂ˜, ÌÂ ‹ ¯ˆÚ›˜ ÙË Û˘Ó¤¯ÈÛË ÙË˜ ¯oÚ‹ÁËÛË˜ ÚÂ‰ÓÈ˙oÏfiÓË˜ ·fi Ùo ÛÙfiÌ·, ÛÂ ÛÙ·‰È·Î‹ ÌÂ›ˆÛË ÙË˜ ‰fiÛË˜ ÛÂ ‰È¿ÛÙËÌ· 4-6 Â‚‰oÌ¿‰ˆÓ, ·Ó¿ÏoÁ· ÌÂ ÙËÓ oÚÂ›· ˘o¯ÒÚË-

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ÛË˜ ÙˆÓ ÎÏÈÓÈÎÒÓ Û˘ÌÙˆÌ¿ÙˆÓ. ∏ ·Ú·¿Óˆ ·ÁˆÁ‹ - ÙÚÂÈ˜ ÒÛÂÈ˜ ÌÂı˘ÏÚÂ‰ÓÈ˙oÏfiÓË˜ ÂÊ·ÚÌfiÛıËÎÂ ÛÙËÓ Û˘ÁÎÂÎÚÈÌ¤ÓË ÂÚ›ÙˆÛË ÌÂ Û˘Ó¤¯ÈÛË ÙË˜ ¯ÔÚ‹ÁËÛË˜ ÚÂ‰ÓÈ˙ÔÏfiÓË˜ ÛÂ ÛÙ·‰È·Î¿ ÌÂÈÔ‡ÌÂÓÂ˜ ‰fiÛÂÈ˜ ·fi ÙÔ ÛÙfiÌ·. ∏ ÎÏÈÓÈÎ‹ ·ÓÙ·fiÎÚÈÛË ÙË˜ ·ÛıÂÓÔ‡˜ ÛÙË ıÂÚ·Â›· ‹Ù·Ó ¿ÌÂÛË, ÌÂ Ï‹ÚË ·ÔÎ·Ù¿ÛÙ·ÛË ‰‡Ô Ì‹ÓÂ˜ ·fi ÙËÓ ÂÈÛ·ÁˆÁ‹. ∏ ÚfiÁÓˆÛË ÙË˜ ÂÁÎ¿ÚÛÈ·˜ Ì˘ÂÏ›ÙÈ‰·˜ ÛÙÔ˘˜ ÂÓ‹ÏÈÎÂ˜ ¤¯ÂÈ ˆ˜ ÂÍ‹˜: ÔÛÔÛÙfi 30% ÙˆÓ ·ÛıÂÓÒÓ ·ÔÎ·ı›ÛÙ·ÓÙ·È Ï‹Úˆ˜, 30% ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‚ÂÏÙ›ˆÛË Î·È 30% Û˘ÓÂ¯›˙Ô˘Ó Ó· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÔ‚·Ú¿ ÓÂ˘ÚÔÏÔÁÈÎ¿ ÂÏÏÂ›ÌÌ·Ù·. ™Ù· ·È‰È¿ Ë ÚfiÁÓˆÛË Ê·›ÓÂÙ·È Ó· Â›Ó·È Î·Ï‡ÙÂÚË, ÌÂ ÔÛÔÛÙfi 60% Ó· ·ÔÎ·ı›ÛÙ·Ù·È Ï‹Úˆ˜ ÛÂ ‰È¿ÛÙËÌ· ÌËÓÒÓ ·fi ÙËÓ ¤Ó·ÚÍË ÙË˜ ÓfiÛÔ˘. ∂È‚·Ú˘ÓÙÈÎÔ› ·Ú¿ÁÔÓÙÂ˜ Â›Ó·È Ë ÔÍÂ›· ÂÁÎ·Ù¿ÛÙ·ÛË Ï‹ÚÔ˘˜ ·Ú¿Ï˘ÛË˜, Ë ·Ú¿Ù·ÛË ÙˆÓ ÛÔ‚·ÚÒÓ ÓÂ˘ÚÔÏÔÁÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ ¤Ú·Ó ÙË˜ Â‚‰ÔÌ¿‰·˜ Î·È Ë Î·ı˘ÛÙ¤ÚËÛË ¤Ó·ÚÍË˜ ‚¿‰ÈÛË˜ ¤Ú·Ó ÙÔ˘ ÌËÓfi˜.

µÈ‚ÏÈoÁÚ·Ê›· 1. Dunne K, Hopkins IJ, Shield LK. Acute transverse myelopathy in childhood. Dev Med Child Neurol 1986;28:198-204. 2. Pittock SJ, Lucchinetti CF. Inflammatory transverse myelitis: evolving concepts. Curr Opin Neurol 2006;19: 362-368. 3. Andronikou S, Albuquerque-Jonathan G, Wilmshurst J, Hewlett R. MRI findings in acute idiopathic transverse myelopathy in children. Pediatr Radiol 2003;33: 624-629. 4. Smith R, Eviatar L. Neurologic manifestations of Mycoplasma pneumoniae infections: diverse spectrum of diseases. A report of six cases and review of the literature. Clin Pediatr (Phila) 2000;39:195-201. 5. Defresne P, Hollenberg H, Husson B, Tabarki B, Landrieu P, Huault G, et al. Acute transverse myelitis in children: clinical course and prognostic factors. J Child Neurol 2003;18:401-406. 6. Miyazawa R, Ikeuchi Y, Tomomasa T, Ushiku H, Ogawa T, Morikawa A. Determinants of prognosis of acute transverse myelitis in children. Pediatr Int 2003; 45:512-516.

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∂˘ÚÂÙ‹ÚÈÔ Û˘ÁÁÚ·Ê¤ˆÓ ÙÔ˘ ∆fiÌÔ˘ 69 Bacchus C. Ellis D. Hall J.G. Holme E. Ikeda H. Logan S. Michalopoulou-Manoloutsiou E. Petersen M.B. Spencer N. Stefopoulou X.M. Sundrum R. Wallace A. ∞ÁÁÂÏ¿ÎÔ˘ µ. ∞ÁÁÂÏ›‰Ô˘ ™. ∞ı·Ó·ÛÈ¿‰Ô˘ º. ∞ı·Ó·Û›Ô˘ ª. ∞ÏÂÍ·Ó‰ÚÔÔ‡ÏÔ˘-∆ÛÈÎÚ›Î· µ. ∞ÏÂÍfiÔ˘ÏÔ˜ ∞. ∞ÏÈÁÈ˙¿ÎË˜ ∞. ∞Ó·ÙÔÏÈˆÙ¿ÎË ª. ∞Ó‰Ú¤Ô˘ ∞. ∞Ó‰ÚÔÓ›ÎÔ˘ ™. ∞ÓıÚ·ÎfiÔ˘ÏÔ˜ ª.µ. ∞ÓÙˆÓÈ¿‰Ë˜ ™. ∞ÓÙˆÓÈ¿‰Ô˘-∫Ô˘Ì¿ÙÔ˘ π. ∞ÓÙˆÓfiÔ˘ÏÔ˜ ∞. ∞ÓÙˆÓÔ‡ÏË ∞. ∞ÚÒÓË ™. ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘ ¶. µ·˙·›Ô˘ ∞. µ·Ì‚·ÎÔ‡‰Ë˜ ∂. µ·Ú‰·ÚÈÓfi˜ ∞. µ·ÚÂÏ¿˜ º. µ·ÚÏ¿ÌË˜ °. µ·ÛÈÏ¿ÎË ¡. µ·ÛÈÏÔÔ‡ÏÔ˘ ª.¡. µÂÏË‚·Û¿ÎË˜ ∂. µÏ¿¯Ô˜ °. µÏ¿¯Ô˘ π. µÔÏ¿ÎË ∫. µÔ‡‰ÚË˜ ∫. µÔ˘Ù˙Ô˘Ú¿ÎË˜ ¡. °·‚Ú›ÏË ™. °·˚Ù·Ó¿ ∫. °·Ï·Ó¿ÎË˜ ∂. °·ÏÏ‹-∆ÛÈÓÔÔ‡ÏÔ˘ ∞. °·Ú‰›ÎË˜ ™. °ÂÚÌ·Ó¿ÎË˜ π. °ÂˆÚÁ¿ÎË ∂. °ÂˆÚÁ·ÎfiÔ˘ÏÔ˜ ¢. °ÂˆÚÁÔ‡ÓÙ˙Ô˘ ∞. °È·ÓÓ·ÎÔÔ‡ÏÔ˘ Ã. °È·ÓÓ·ÎÔ‡ÏÈ· ª. °È·ÙÚÔÌ·ÓˆÏ¿ÎË ∞. °ÎÚ¿Ù˙ÈÔ˘ Ã. °Ô˘‰ÂÛ›‰Ô˘ ª. ¢¿ÎÔ˘-µÔ˘ÙÂÙ¿ÎË ∞. ¶·È‰È·ÙÚÈÎ‹ 2006;69:484-485

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ª·Ú›· ¶··Ê›ÏË °È· ÏËÚÔÊÔÚ›Â˜: www.euran.com ªaria Papafili For information: www.euran.com

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10-11 ¡ÔÂÌ‚Ú›Ô˘ 2006

5Ô ™ÂÌÈÓ¿ÚÈÔ ÌÂ ı¤Ì·: æ˘¯ÔÎÔÈÓˆÓÈÎ‹ ™Ù‹ÚÈÍË ÙÔ˘ ¶·È‰ÈÔ‡ ÌÂ ∫·ÚÎ›ÓÔ Î·È ÙË˜ √ÈÎÔÁ¤ÓÂÈ¿˜ ÙÔ˘ •ÂÓÔ‰Ô¯Â›Ô Holiday Inn ¢ÈÔÚÁ¿ÓˆÛË: √ÁÎÔÏÔÁÈÎﬁ ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞ÁÏ·˝· ∫˘ÚÈ·ÎÔ‡” ∆ËÏ.: 210 7254360-2 Fax: 210 7254363 ∂-mail: info@epsiloncongress.gr Website: www.epsiloncongress.gr

∞ı‹Ó·

15-17 ¡ÔÂÌ‚Ú›Ô˘ 2006

Advanced Minimally Invasive Operating Techniques in Paediatric Surgery Contact: European Surgical Institute Tel.: 49-0-4-052-973-200 Fax: 49-0-4-052-973-209 E-mail: info@esi-online.de

Norderstedt, Germany

15 - 18 ¡ÔÂÌ‚Ú›Ô˘ 2006 Infant, Child and Adolescent Medicine Contact: Karla Krause Tel: 800-274-2237, ext. 6522 Fax: 913-906-6092 E-mail: kkrause@aafp.org

St. Petersburg, FL, United States

25-26 ¡ÔÂÌ‚Ú›Ô˘ 2006

6Ë ¢ÈËÌÂÚ›‰· ∫ÔÈÓˆÓÈÎ‹˜ ¶·È‰È·ÙÚÈÎ‹˜ ∞ÌÊÈı¤·ÙÚÔ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ ¡ÔÛÔÎÔÌÂ›Ô˘ ¢ÈÔÚÁ¿ÓˆÛË: ∂ÏÏËÓÈ‹ ∂Ù·ÈÚ›· ∫ÔÈÓˆÓÈÎ‹˜ ¶·È‰È·ÙÚÈÎ‹˜ Î·È ¶ÚÔ·ÁˆÁ‹˜ ÙË˜ ÀÁÂ›·˜ ¶·Ú¿ÚÙËÌ· £ÂÛÛ·Ï›·˜ Î·È ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·Ï›·˜ ∆ËÏ.: 2410 682705, 6937 676725

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29 ¡ÔÂÌ‚Ú›Ô˘ 3 ¢ÂÎÂÌ‚Ú›Ô˘ 2006

3rd International POSNA/AAOS Pediatric Orthopaedic Symposium Contact: Susan McSorley Tel.: 847-823-7186 Fax: 847-823-8125 E-mail: mcsorley@aaos.org

Orlando, United States

20 - 21 π·ÓÔ˘·Ú›Ô˘ 2007 17o ™˘Ó¤‰ÚÈÔ ¶·È‰È·ÙÚÈÎ‹˜ ∫ÏÈÓÈÎ‹˜ ™˘ÓÂ‰ÚÈ·Îfi & ¶ÔÏÈÙÈÛÙÈÎfi ∫¤ÓÙÚÔ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ ¶·È‰È·ÙÚÈÎ‹ ∫ÏÈÓÈÎ‹ ¶·Ó/Ì›Ô˘ ¶·ÙÚÒÓ, ∫·ı. ™Ù. ª·ÓÙ·Áfi˜ ™˘ÓÂ‰ÚÈ·Îfi & ¶ÔÏÈÙÈÛÙÈÎfi ∫¤ÓÙÚÔ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ ∆ËÏ.: 2610-993999 Fax: 2610-994999 ∂-mail: confer@upatras.gr Website: www.confer.upatras.gr

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25-27 π·ÓÔ˘·Ú›Ô˘ 2007 25th Annual Conference on Sleep Disorders in Infancy & Childhood Contact: Alice Clark Tel.: 760-773-4500 Fax: 760-773-4551 E-mail: sleep@annenberg.net

Rancho Mirage, CA, United States

xxvi

7-10 ºÂ‚ÚÔ˘·Ú›Ô˘ 2007 16th Annual Pediatric Infectious Diseases Contact: Janis Pearson / Joan Sweeney Tel.: 220-7032 / 220-8458 E-mail: pearsonj@ucalgary.ca / sweeney@ucalgary.ca

Calgary, AB, Canada

17-24 ºÂ‚ÚÔ˘·Ú›Ô˘ 2007 8th JOPEOI (European / Indian Ocean Meeting about Mother & Child Health Contact: Kamel Bargaoui Tel.:33-607-686-118 Fax: 33-143-839-985 E-mail: kamel@medicom-international.com

Dubai, United Arab Emirates

8-11 ª·ÚÙ›Ô˘ 2007

Pediatric Anesthesiology 2007 Contact: Society for Pediatric Anesthesia Tel.:804-282-9780 Fax: 804-282-0090 E-mail: spa@societyhq.com

Phoenix, AZ, United States

16-18 ∞ÚÈÏ›Ô˘ 2007

The 7th Annual International Neonatology Symposium Contact: Saleh Al-Alaiyan, MD Tel.:00-96-614-427-762 Fax: 00-96-614-427-784 E-mail: alaiyan@kfshrc.edu.sa

Riyadh, Saudi Arabia

2-5 ª·˝Ô˘ 2007

15th TRANSMED: 15th European/Mediterranean Congress about Mother & Child Health Contact: Kamel BARGAOUI Tel.:33-607-686-118 Fax: 33-143-839-985 E-mail: kamel@medicom-international.com

Cairo, Egypt

2-5 ª·˝Ô˘ 2007

33Ô ∂Ù‹ÛÈÔ ¶·ÓÂÏÏ‹ÓÈÔ π·ÙÚÈÎﬁ ™˘Ó¤‰ÚÈÔ •ÂÓÔ‰Ô¯Â›Ô Hilton ¢ÈÔÁ¿ÓˆÛË: π·ÙÚÈÎ‹ ∂Ù·ÈÚÂ›· ∞ıËÓÒÓ ª·È¿Ó‰ÚÔ˘ 23, 11528, ∞ı‹Ó· ∆ËÏ.: 210 7211845 Fax: 210 7215082 E-mail: iea@mednet.gr

∞ı‹Ó·

7 - 10 πÔ˘Ó›Ô˘ 2007

5Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ¶·È‰Ô„˘¯È·ÙÚÈÎ‹˜ ∂Ù·ÈÚÂ›·˜ ∂ÏÏ¿‰Ô˜ ª¤Á·ÚÔ ªÔ˘ÛÈÎ‹˜ ∞ıËÓÒÓ ¢ÈÔÚÁ¿ÓˆÛË: ¶·È‰Ô„˘¯È·ÙÚÈÎ‹ ∂Ù·ÈÚÂ›· ∂ÏÏ¿‰Ô˜ ¶ÏËÚÔÊÔÚ›Â˜: AC&C International ∆ËÏ: 210 6889100 Fax: 210 6844777 E-mail: info@acnc.gr

∞ı‹Ó·

14-17 πÔ˘Ó›Ô˘ 2007

The 21st Congress of International Association of Paediatric Dentistry Contact: Agnes Chung / Daniel Chok Tel.:85-228-718-896 / 28-718-815 Fax: 85-228-718-898 E-mail: info@iapd2007.com

Hong Kong, Hong Kong