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ªÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· Û ·È‰È¿ Î·È Ó¤Ô˘˜. ¶ÚÒÙË ÈÏÔÙÈ΋ ÌÂϤÙË ÛÙËÓ ∫Ú‹ÙË∂. ªÈ¯·ËÏ›‰Ô˘1, Ã. §ÈÔÓ‹˜3, ª. ™ËÏÈÒÙË2, ¶. ¶·Û·Ï¿ÎË1, ¶. ¡ÈÎËÙ¿Î˘3, ∂. ¶··‰ÔÔ‡ÏÔ˘1, ¡. ∫·Ù˙ËÏ¿Î˘1, Œ. ∆Û·¿ÎË1, ∏. ª·ÓÈ·‰¿ÎË1, ¶. µÔÚÁÈ¿1, ∞. ∫·ÓÈÙÛ¿Î˘4, ∂. ∫fiÎÔÚË5, R. A. Wevers6, ™. ™Ì˘Ú¿ÎȘ1, ∞. ∂˘·ÁÁÂÏ›Ô˘2

Inherited metabolic disorders in children and young adults. First pilot study in CreteH. Michailidou1, C. Lionis3, M. Spilioti2, P. Paspalaki1, P. Nikitakis3, E. Papadopoulou1, N. Katzilakis1, E. Tsapaki1, H. Maniadaki1, P. Vorgia1, A. Kanitsakis4, E. Kokori5, R. A. Wevers6, S. Sbyrakis1, A. Evangeliou2

∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞ ORIGINAL ARTICLE

�¶ÂÚ›ÏË„Ë: T· ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·Û˘¯Ó¿ ˘Ô‰È·ÁÈÁÓÒÛÎÔÓÙ·È. O ÛÎÔfi˜ Ù˘ ÈÏÔÙÈ-΋˜ ·˘Ù‹˜ ÌÂϤÙ˘ Â›Ó·È Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ Ù· ÚÒÙ··ÔÙÂϤÛÌ·Ù· Î·È ÙËÓ ÂÌÂÈÚ›· Ô˘ ·ÔÎÙ‹ıËηfi ÙË Û˘ÓÂÚÁ·Û›· È·ÙÚÒÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·È ÛÙËÓÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜ Û ·ÁÚÔÙÈΤ˜ ÂÚÈÔ-¯¤˜ Ù˘ ∫Ú‹Ù˘ Ì ¤Ó· ÂÍÂȉÈÎÂ˘Ì¤ÓÔ ·ÓÂÈÛÙË-ÌÈ·Îfi ΤÓÙÚÔ. OÈ ÁÈ·ÙÚÔ› Ô˘ ÂÚÁ¿˙ÔÓÙ·È Û 8 Τ-ÓÙÚ· ˘Á›·˜ ÛÙËÓ ·ÁÚÔÙÈ΋ ÂÚÈÔ¯‹ Ù˘ ∫Ú‹Ù˘(·È‰›·ÙÚÔÈ Î·È ÁÂÓÈÎÔ› È·ÙÚÔ›) ·Ú¤ÂÌ„·Ó 112·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Û·Ó ¤Ó· ÙÔ˘Ï¿¯ÈÛÙÔÓ ·fi Ù·ÎÚÈÙ‹ÚÈ· (Û˘ÌÙÒÌ·Ù· ‹ ¯·Ú·ÎÙËÚÈÛÙÈο) ÂÓfi˜ÂÚˆÙËÌ·ÙÔÏÔÁ›Ô˘ Ô˘ ÙÔ˘˜ ›¯Â ‰È·ÓÂÌËı›, ÛÙÔ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ, Ì ÙËÓ˘Ô„›· ÂÓ‰ÔÁÂÓÔ‡˜ ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜. ªÂÙ¿·fi ÂÍÂȉÈÎÂ˘Ì¤ÓÔ ÎÏÈÓÈÎfi, ÂÚÁ·ÛÙËÚÈ·Îfi Î·È ·ÂÈ-ÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô Û 17/112 ·ÛıÂÓ›˜ (15,2%) ÂÈ-‚‚·ÈÒıËÎÂ Ë ‰È¿ÁÓˆÛË ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜.¢Âη٤ÛÛÂÚȘ ·fi ÙÔ˘˜ 17 ·ÛıÂÓ›˜ ‹Ù·Ó ·È‰È¿.™ÙÔ˘˜ ·ÛıÂÓ›˜ ÂÊ·ÚÌfiÛÙËÎÂ, fiÔ˘ ‹Ù·Ó ‰˘Ó·Ùfi,Ë Î·Ù¿ÏÏËÏË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ÂÓÒÛÙÔ˘˜ ›‰ÈÔ˘˜ Î·È ÙȘ ÔÈÎÔÁ¤ÓÂȤ˜ ÙÔ˘˜ ·Ú·Û¯¤ıË-Ποı ‰˘Ó·Ù‹ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË.¶·Ú¿ÏÏËÏ·, ¤ÁÈÓ ÁÂÓÂÙÈ΋ ηıÔ‰‹ÁËÛË Î·È Û˘Ì-‚Ô˘Ï¢ÙÈ΋ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜ ÙˆÓ ·Û¯fiÓÙˆÓ. ∏Û˘Ì‚ÔÏ‹ ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›-‰·˜ ˘Á›·˜ ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË ÙˆÓ ÌÂÙ·‚ÔÏÈ-ÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÛÙ· ·È‰È¿ Ê·›ÓÂÙ·È Ó· Â›Ó·È ÛËÌ·-ÓÙÈ΋, ηıfiÛÔÓ Ì ÙËÓ Î·Ù¿ÏÏËÏË Âη›‰Â˘ÛË Î·È

�Abstract: Inherited metabolic disorders are oftenunderdiagnosed. The aim of this pilot study is topresent the main outcomes and the experiencegained as a result of the cooperation between themedical staff of the primary health care system in therural areas of Crete and the tertiary care doctors atthe referral University Hospital of Heraklion, Crete.Medical staff working in 8 primary health carecenters in rural Crete (pediatricians and generalpractitioners) referred 112 patients suspected formetabolic disease who fulfilled at least 1 criterion(symptom or sign) from a pre-constructedquestionnaire. After detailed clinical and laboratoryinvestigations 17 of 112 patients (15.2 %) were foundto have an inherited metabolic disease. Fourteen ofthese patients were children. Where possible, thesepatients were provided with the appropriatetreatment. Additionally, socio-economical supportand genetic consultation was made available to all ofthem and their families. A high index of suspicion,proper training and supply of information to theprimary health care physicians may contribute to thetimely detection of patients with inherited metabolicdiseases and the prevention and treatment of newcases.

1 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¶ÂÚÈÊÂÚÂÈ·Îfi ¶·ÓÂÈÛÙËÌÈ·Îfi °ÂÓÈÎfi¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ (¶∂¶∞°¡∏), ∫Ú‹ÙË

2 ¡Â˘ÚÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, ¶∂¶∞°¡∏, ∫Ú‹ÙË 3 ∆Ô̤·˜ ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜, ¶∂¶∞°¡∏, ∫Ú‹ÙË 4 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô Ã·Ó›ˆÓ, ∫Ú‹ÙË 5 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, µÂÓÈ˙¤ÏÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô

∏Ú·ÎÏ›Ԣ, ∫Ú‹ÙË 6 University Hospital Nigmegen, The Netherlands

Department of Neurology and Pediatrics

1 Department of Pediatrics, Medical School, University ofHeraklion, Crete

2 Department of Neurology, Medical School, University ofHeraklion, Crete

3 Department of Public Health and Social Medicine, MedicalSchool, University of Heraklion, Crete

4 Pediatric Clinic, General Hospital of Chania, Crete 5 Department of Pediatrics, Venizelio General Hospital of

Heraklion, Crete 6 University Hospital Nigmegen, The Netherlands

Department of Neurology and Pediatrics

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∂ÈÛ·ÁˆÁ‹OÈ ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡

‰ÂÓ Â›Ó·È ÙfiÛÔ Û¿ÓȘ fiÛÔ ÈÛÙ¢fiÙ·Ó ÚÈÓ ÌÂÚÈο¯ÚfiÓÈ· (1-4). ªÂ ÙËÓ ·Ó¿Ù˘ÍË Ù˘ Ù¯ÓÔÏÔÁ›·˜ ηÈÙ˘ ¤Ú¢ӷ˜ fiÏÔ Î·È ÈÔ Û˘¯Ó¿ ‰È·ÁÈÁÓÒÛÎÔÓÙ·ÈÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·, ÌÂÚÈο ·fi Ù· ÔÔ›· ÁÈ·ÚÒÙË ÊÔÚ¿, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ¤ÁηÈÚË, Û˘¯Ó¿,¤Ó·ÚÍË ·ÔÙÂÏÂÛÌ·ÙÈ΋˜ ıÂڷ¢ÙÈ΋˜ ·ÁˆÁ‹˜Î·È ÚÔÏËÙÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ (5,6).

∏ ÌÂϤÙË ÙˆÓ ÂÓ‰ÔÁÂÓÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿-ÙˆÓ (∂ª¡) ÛÙËÓ ∫Ú‹ÙË, ¤Ó· ÓËÛ› Ì ÏËı˘ÛÌfi ÌÂ-Á·Ï‡ÙÂÚÔ ·fi 500.000 ηÙÔ›ÎÔ˘˜, ·ÔÎÙ¿ ȉȷ›ÙÂ-ÚÔ ÂӉȷʤÚÔÓ Î·ıÒ˜:

·) ∏ ÏÂÈÔ„ËÊ›· ÙˆÓ ÁÈ·ÙÚÒÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·ÓÛÙ· ΤÓÙÚ· ˘Á›·˜ ̤¯ÚÈ ÚfiÛÊ·Ù· ‹Ù·Ó ·ÓÂȉ›-΢ÙÔÈ Ô˘ ÂÎÏ‹ÚˆÓ·Ó ÙËÓ ˘Ô¯ÚˆÙÈ΋ ıËÙ›·˘·›ıÚÔ˘, ¯ˆÚ›˜ ÙËÓ Î·Ù¿ÏÏËÏË Âη›‰Â˘ÛË Î·ÈÂÌÂÈÚ›· ÒÛÙ ӷ ·Ó·ÁÓˆÚ›˙Ô˘Ó ¤ÁηÈÚ· ÙȘ ÎÏÈÓÈ-Τ˜ ÂΉËÏÒÛÂȘ ÙˆÓ Ó¢ÚÔÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿-ÙˆÓ. ™ÙÔ˘˜ ÁÈ·ÙÚÔ‡˜ ·˘ÙÔ‡˜ ‰ÂÓ ‹Ù·Ó ÚÔÛÈÙ‹ Ë ‚È-‚ÏÈÔÁÚ·Ê›· ÁÈ· ÙȘ ÚfiÛÊ·Ù˜ ÂÍÂÏ›ÍÂȘ Î·È ‰˘Ó·-ÙfiÙËÙ˜ Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜ Î·È ‚ÈÔ¯ËÌ›·˜ÛÙË ‰È¿ÁÓˆÛË ÙˆÓ Ó¢ÚÔÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓÛÙËÓ ∂ÏÏ¿‰· Î·È ÙÔ Â͈ÙÂÚÈÎfi.

‚) ™ÙȘ ·ÔÌÔӈ̤Ó˜ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘∫Ú‹Ù˘, fiÔ˘ Ê·›ÓÂÙ·È fiÙÈ ÂÓÙÔ›˙ÂÙ·È Ë ÏÂÈÔÓfi-ÙËÙ· ÙˆÓ ·‰È¿ÁÓˆÛÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ,˘¿Ú¯Ô˘Ó ȉȷ›ÙÂÚ˜ ÎÔÈÓˆÓÈΤ˜ Î·È ÔÏÈÙÈÛÌÈΤ˜Û˘Óı‹Î˜, οÙÈ Ô˘ Â›Ó·È Èı·Ófi Ó· ηıÈÛÙ¿ ÙËÓ·ʋ Ì ÙÔÓ È·ÙÚfi ‰‡ÛÎÔÏË.

Á) ∆Ô ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô Ù˘ ∫Ú‹Ù˘ÛÙÔ ∏Ú¿ÎÏÂÈÔ, ÙÔ ÔÔ›Ô ‚Ú›ÛÎÂÙ·È ÛÙÔ Ì¤ÛÔ Ù˘ Ó‹-ÛÔ˘, ÏÂÈÙÔ˘ÚÁ› Â‰Ò Î·È 12 ¯ÚfiÓÈ·. ŸÌˆ˜, Ù· ÙÂ-ÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤ÁÈÓ ȉȷ›ÙÂÚË ÚÔÛ¿ıÂÈ· ÁÈ· ÙËÓ·Ó¿Ù˘ÍË Ù˘ ÌÔÓ¿‰·˜ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓÛÙËÓ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋. øÛÙfiÛÔ, ÚԤ΢„·Ó ·Ú-ÎÂÙ¤˜ ‰˘ÛÎÔϛ˜ ÁÈ·Ù› ÂÎÙfi˜ ·fi ÙËÓ ·Ó·Ú΋ ÂÓË-̤ڈÛË ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›-‰·˜ ˘Á›·˜ (¶ºÀ), ˘¿Ú¯Ô˘Ó ÔÏϤ˜ ·ÔÌÔӈ̤-Ó˜ Î·È ‰˘ÛÚfiÛÈÙ˜ ÂÚÈÔ¯¤˜ Û ̷ÎÚÈÓ¤˜ ·Ô-ÛÙ¿ÛÂȘ fiÔ˘ Ë ÂÈÎÔÈÓˆÓ›· Â›Ó·È ‰‡ÛÎÔÏË.

∏ ÁÂÓÈ΋ È·ÙÚÈ΋ ıˆÚÂ›Ù·È ˆ˜ ·ÓÂÍ¿ÚÙËÙË È·-ÙÚÈ΋ ÂȉÈÎfiÙËÙ· ÛÙËÓ ∂ÏÏ¿‰· ηٿ ÙË ‰È¿ÚÎÂÈ·ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ ÂÙÒÓ. ™ÙËÓ ∫Ú‹ÙË, fiÔ˘ ÙÔ ÙÌ‹Ì·π·ÙÚÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ¤¯ÂÈ Î·ıÈÂÚÒÛÂÈ Âη›-

‰Â˘ÛË Î·È Ú·ÎÙÈ΋ ¿ÛÎËÛË ÛÙËÓ ¶ºÀ, ÏÂÈÙÔ˘ÚÁ›ٷ ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤Ó· ‰›ÎÙ˘Ô ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË˜Û˘ÓÂÚÁ·Û›·˜ ÙÔ˘ ∆Ô̤· ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ Î·È 10ΤÓÙÚˆÓ ˘Á›·˜. ∂ÈϤÔÓ, Â›Ó·È È‰È·›ÙÂÚ· ÛËÌ·ÓÙÈ-Îfi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÌÂÙ¿ ÙÔ 1995 ÂÎÙfi˜ ·fi ÙÔ˘˜ ÂÈ-‰ÈÎÂ˘Ì¤ÓÔ˘˜ ÁÂÓÈÎÔ‡˜ È·ÙÚÔ‡˜, ÂȉÈÎÂ˘Ì¤ÓÔÈ ·È-‰›·ÙÚÔÈ ÛÙÂϯÒÓÔ˘Ó Ù· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· ˘Á›-·˜ ÛÙËÓ ∫Ú‹ÙË. ™ËÌ·ÓÙÈ΋, ›Û˘, Ù· ÙÂÏÂ˘Ù·›·¯ÚfiÓÈ· ‹Ù·Ó Î·È Ë ÚÔÛ¿ıÂÈ· Û˘ÓÂÚÁ·Û›·˜ ÌÂÙ·-͇ Ù˘ ∫ÏÈÓÈ΋˜ ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ ÙÔ˘ ¶·ÓÂÈ-ÛÙËÌ›Ô˘ ∫Ú‹Ù˘ Î·È Ù˘ ªÔÓ¿‰·˜ ªÂÙ·‚ÔÏÈÎÒÓ¡fiÛˆÓ Ù˘ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙË-ÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ ∏Ú·ÎÏ›Ԣ (¶·°¡∏),Ì ÛÎÔfi ÙËÓ ·Ó›¯Ó¢ÛË Î·È ¤ÁηÈÚË ‰È¿ÁÓˆÛË ÙˆÓÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÛÙËÓ ∫Ú‹ÙË. ∏ ‰ÈÂÚ‡ÓË-ÛË ÙÔ˘ ÚfiÏÔ˘ Î·È Ù˘ Û˘Ì‚ÔÏ‹˜ ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘¶ºÀ ÛÙËÓ ·Ó›¯Ó¢ÛË Î·È Î·ıÔ‰‹ÁËÛË ·ÙfiÌˆÓ Ì¢fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÛÙȘ ‰˘ÛÚfiÛÈÙ˜·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘ ∫Ú‹Ù˘ ·ÔÙÂÏ› ¤Ó· ÂÍ·È-ÚÂÙÈο ÂӉȷʤÚÔÓ ÎÏÈÓÈÎfi ı¤Ì·. °È· ÙÔ ÛÎÔfi ·˘-Ùfi Û˘ÓÂÚÁ¿ÛÙËÎ·Ó ÔÈ ¶·È‰È·ÙÚÈΤ˜ ∫ÏÈÓÈΤ˜ ÙÔ˘¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘, ÙÔ˘ µÂÓÈ˙¤ÏÂÈÔ˘ ¡ÔÛÔÎÔ-Ì›Ԣ Î·È ÙˆÓ Ã·Ó›ˆÓ, Ë ¡Â˘ÚÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ Î·È Ô∆Ô̤·˜ ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘∫Ú‹Ù˘ Ì 8 ΤÓÙÚ· ˘Á›·˜ ÛÙȘ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ-¯¤˜ Ù˘ ∫Ú‹Ù˘. O ÛÎÔfi˜ ·˘Ù‹˜ Ù˘ ÈÏÔÙÈ΋˜ ÌÂ-ϤÙ˘ Â›Ó·È Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ Ù· ÚÒÙ· ·ÔÙÂϤÛÌ·-Ù· Î·È ÙËÓ ÂÌÂÈÚ›· ·fi ·˘Ù‹ ÙË Û˘ÓÂÚÁ·Û›· Î·È Ó·Û˘˙ËÙ‹ÛÂÈ ÙË Û˘Ì‚ÔÏ‹ ÙˆÓ ÁÈ·ÙÚÒÓ Ô˘ ÂÚÁ¿˙Ô-ÓÙ·È ÛÙË ÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜ ÛÙË ‰È¿-ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÂÓ‰ÔÁÂÓ‹ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ∏ ÌÂϤÙË ‰ÈÂÍ‹¯ıË Î·Ù¿ ÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 1997-1999

ÛÙËÓ ·ÁÚÔÙÈ΋ ÂÚÈʤÚÂÈ· Ù˘ ∫Ú‹Ù˘. ™˘ÌÂÚÈÏ‹ÊıËÎ·Ó 8ΤÓÙÚ· ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÛÙÔ ÓËÛ› (™‹ÏÈ,¶¤Ú·Ì·, ∞ÓÒÁÂÈ·, ∫¿ÓÙ·ÓÔ˜, ∫·ÛÙ¤ÏÏÈ, ªÔ›Ú˜, ∞Ú¯¿Ó˜ ηȡ¿ÔÏȘ) (∂ÈÎfiÓ· 1).

OÎÙÒ ÂȉÈÎÂ˘Ì¤ÓÔÈ È·ÙÚÔ› ÙˆÓ Î¤ÓÙÚˆÓ ·˘ÙÒÓ (4 ÁÂÓÈÎÔ› È·-ÙÚÔ›, 4 ·È‰›·ÙÚÔÈ) ÂÎÏ‹ıËÛ·Ó Î·È Û˘ÌÌÂÙ›¯·Ó Û ÂÎ·È‰Â˘ÙÈ-Τ˜ ÚÔηٷÚÎÙÈΤ˜ Û˘Ó·ÓÙ‹ÛÂȘ ÛÙÔ ¶·ÓÂÈÛÙ‹ÌÈÔ ∫Ú‹Ù˘.¶ÚÈÓ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÚÔÁÚ¿ÌÌ·ÙÔ˜, ηıÔÚ›ÛÙËΠ¤Ó·˜ η-Ù¿ÏÔÁÔ˜ Ì ÎÚÈÙ‹ÚÈ· ÂÈÛ·ÁˆÁ‹˜ ·ÛıÂÓÒÓ ÛÙË ÌÂϤÙË Ô˘ ‚·-Û›ÛÙËΠ۠ÂȉÈο ‹ ÌË ÂȉÈο ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ηÈ

ÂÓË̤ڈÛË ÌÔÚÔ‡Ó Ó· ·ÓȯÓÂ‡Ô˘Ó ¤ÁηÈÚ· ·ÛıÂ-Ó›˜ Ì ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ Î·È Ó· η-Ù¢ı‡ÓÔ˘Ó ÛÙË ÛˆÛÙ‹ ÚÔÏËÙÈ΋ Î·È ıÂڷ¢ÙÈ΋·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÓÔÛËÌ¿ÙˆÓ ·˘ÙÒÓ.

§¤ÍÂȘ ÎÏÂȉȿ: ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·,ÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜.

Key words: inherited metabolic diseases, primaryhealth care.

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·134

Û˘ÌÙÒÌ·Ù· Ô˘ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì ÌÂ-Ù·‚ÔÏÈο ÓÔÛ‹Ì·Ù· (7-9). O ηٿÏÔÁÔ˜ Ì ٷ ÎÚÈÙ‹ÚÈ·, Û‡Ì-ʈӷ Ì ٷ ÔÔ›· ÔÈ ·ÛıÂÓ›˜ ·Ú·¤ÌÊıËÎ·Ó Ì ÙËÓ ˘fi-ÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔ-ÌÂ›Ô ∏Ú·ÎÏ›Ԣ, Ê·›ÓÂÙ·È ÛÙÔÓ ¶›Ó·Î· 1. OÈ ÁÈ·ÙÚÔ› Ù˘ Úˆ-ÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ¤ÏÂÁ¯·Ó ÙËÓ ·ÚÔ˘Û›· ÙˆÓ ÎÚÈ-ÙËÚ›ˆÓ ·˘ÙÒÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ÙÔ˘˜ Î·È ·Ú¤ÂÌ·Ó ·ÛıÂÓ›˜Ì 1 ‹ ÂÚÈÛÛfiÙÂÚ· ÎÚÈÙ‹ÚÈ· ÛÙË ÌÔÓ¿‰· ÂÓ‰ÔÁÂÓÒÓ ÓÔÛË-Ì¿ÙˆÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ ¶·-ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘, Ë ÔÔ›· ÏÂÈÙÔ˘ÚÁ› ÛÙÔ ¶·°¡∏.

∞ÎÔÏÔ‡ıˆ˜, ÔÈ È·ÙÚÔ› Ù˘ ÌÔÓ¿‰·˜, ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÙË¡Â˘ÚÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ÙÔ˘ ›‰ÈÔ˘ ¡ÔÛÔÎÔÌ›Ԣ, ÂÊ¿ÚÌÔ˙·Ó ÏÂ-ÙÔÌÂÚ‹ ÎÏÈÓÈ΋ Ó¢ÚÔÏÔÁÈ΋ ÂͤٷÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘·Ú·¤ÌÊıËÎ·Ó Î·È ·Ó¿ÏÔÁ· ÚÔ¯ˆÚÔ‡Û·Ó Û ÂÍÂȉÈÎÂ˘Ì¤-ÓÔ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô. O ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Ô˘·ÎÔÏÔ‡ıËÛ ÛÙËÚ›¯ıËΠÛÙËÓ ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›·, ÛÙÔÈÛÙÔÚÈÎfi Î·È ÙËÓ ÂȉÈ΋ ηÙ‡ı˘ÓÛË Ô˘ ‰fiıËΠ̠‚¿ÛË ÙȘÈı·Ó¤˜ ‰È·ÁÓÒÛÂȘ Ô˘ ηıÔÚ›ÛÙËÎ·Ó ·fi ·È‰ÔÓ¢ÚÔÏfi-ÁÔ. ™Â fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ¤ÁÈÓ ·Ó¿Ï˘ÛË ·›Ì·ÙÔ˜ (ÁÂÓÈ΋ÂͤٷÛË ·›Ì·ÙÔ˜ Î·È ÚÔÛ‰ÈÔÚÈÛÌfi˜: ËÏÂÎÙÚÔÏ˘ÙÒÓ, ÙÚ·Ó-Û·ÌÈÓ·ÛÒÓ, ÁÏ˘Îfi˙˘, ·ÂÚ›ˆÓ ·›Ì·ÙÔ˜, ÎÚ·ÙÈÓ›Ó˘, Ô˘Ú›·˜,Ô˘ÚÈÎÔ‡ ÔͤԘ, ÎÚ·ÙÈÓÔʈÛÊÔÎÈÓ¿Û˘ (CPK), ·ÏηÏÈ΋˜ÊˆÛÊ·Ù¿Û˘, Á·Ï·ÎÙÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘ (LDH), ÙÚÈÁÏ˘ÎÂ-Úȉ›ˆÓ, ¯ÔÏËÛÙÂÚfiÏ˘, Ì˘ÔÛÊ·ÈÚ›Ó˘, ÊÂÚÈÙÙ›Ó˘).

∞Ó¿ÏÔÁ· Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È È‰È·›ÙÂÚ· › ˘Ô„›·˜ÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂÈ·˜, ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ‹ ·ÌÈÓÔÍÂÔ¿ıÂÈ-·˜, ¤ÁÈÓ·Ó ÌÂÙÚ‹ÛÂȘ Á·Ï·ÎÙÈÎÔ‡ ÔͤԘ, ˘ÚÔÛÙ·Ê˘ÏÈÎÔ‡ÔͤԘ, ·ÎÂÙ˘Ï·ÎÂÙÔÍÈÎÔ‡, ‚-O∏ ‚Ô˘Ù˘ÚÈÎÔ‡ ÔͤԘ, ·Ì̈-Ó›·˜ Î·È Î·ÚÓÈÙ›Ó˘.

∂ÈϤÔÓ, ¤ÁÈÓ ËÏÂÎÙÚÔÂÁÎÂÊ·ÏÔÁÚ¿ÊËÌ· (∏∂°), ·ÍÔÓÈ-΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ (CT scan) ηÈ, fiÔ˘ ÎÚ›ıËΠÛÎfi-ÈÌÔ, Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ (MRI). ∂›Û˘, ÂϤÁ-¯ıËÎ·Ó Ù· Ô‡Ú· ÙˆÓ ·ÛıÂÓÒÓ (‚ÈÔ¯ËÌÈ΋, ÌÈÎÚÔÛÎÔÈ΋ ·Ó¿-Ï˘ÛË, ¯ÚÒÌ·, ÔÛÌ‹, FeCl3 test, ·Ó·ÁˆÁÈΤ˜ Ô˘Û›Â˜). ªÂ ‚¿ÛËÙ· ·ÔÙÂϤÛÌ·Ù· ·fi ÙÔÓ ·Ú¯ÈÎfi ÂÚÁ·ÛÙËÚÈ·Îfi Î·È ·ÂÈÎÔÓÈ-ÛÙÈÎfi ¤ÏÂÁ¯Ô ¤ÁÈÓ ¤ÏÂÁ¯Ô˜ ÁÈ· ÔÚÁ·ÓÈΤ˜ ÔÍÂÔ˘Ú›Â˜ (·Ó¿Ï˘-ÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Ô‡ÚˆÓ Ì GC/MS), ÚÔÛ‰ÈÔÚÈÛÌfi˜ ·ÌÈ-ÓÔͤˆÓ ÛÙÔ Ï¿ÛÌ· Î·È Ù· Ô‡Ú·, ÂÓÒ Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒ-ÛÂȘ Ú·ÁÌ·ÙÔÔÈ‹ıËΠ·Ó¿Ï˘ÛË VLCFA (very long chainfatty acids) ÛÙÔÓ ÔÚfi. ™Â ÂÈÏÂÁ̤Ó˜ ÂÚÈÙÒÛÂȘ ¤ÁÈÓ ÊfiÚ-

ÙÈÛË Ì ÁÏ˘Îfi˙Ë, ÊÚÔ˘ÎÙfi˙Ë, Ê·ÈÓ˘ÏÚÔÈÔÓÈÎfi Ô͇ Î·È Ï‡-Έ̷. ∂ÎÙfi˜ ·fi ÙÔÓ ÂȉÈÎfi ÂÚÁ·ÛÙËÚÈ·Îfi Î·È ·ÂÈÎÔÓÈÛÙÈÎfi¤ÏÂÁ¯Ô, ¤ÁÈÓ·Ó ÂÈÏÂÎÙÈο ÂÚÈÛÛfiÙÂÚÔ ÂÍÂȉÈÎÂ˘Ì¤Ó˜ ÂÍÂÙ¿-ÛÂȘ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÙÂı› ÔÚÈÛÙÈο Ë ‰È¿ÁÓˆÛË, fiˆ˜ ÚÔÛ-‰ÈÔÚÈÛÌfi˜ ÂÓ˙‡ÌˆÓ Û ‰È¿ÊÔÚÔ˘˜ ÈÛÙÔ‡˜ Î·È ‚ÈÔÏÔÁÈο ˘ÁÚ¿(·›Ì·, ÈÓÔ‚Ï¿ÛÙ˜, ̇˜, ‹·Ú), fiˆ˜ ›Û˘ ·Ó¿Ï˘ÛË ÁÂÓÂ-ÙÈÎÔ‡ ˘ÏÈÎÔ‡ Û ·ÙÙ·Ú· ·›Ì·ÙÔ˜ Î·È Ì˘˚ο ·ÙÙ·Ú· ÁÈ· ·Ó›-¯Ó¢ÛË ÁÓˆÛÙÒÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Û ˘ÚËÓÈÎfi ‹ ÌÈÙÔ¯ÔÓ‰ÚÈ·Îfi˘ÏÈÎfi. ∏ ‚Ô‹ıÂÈ· ÂȉÈÎÒÓ ·È‰È·ÙÚÈÎÒÓ Î·È Ó¢ÚÔÌÂÙ·‚ÔÏÈÎÒÓΤÓÙÚˆÓ ÙÔ˘ ÂÛˆÙÂÚÈÎÔ‡ Î·È Â͈ÙÂÚÈÎÔ‡ ˘‹ÚÍ ÔχÙÈÌË.

∞ÔÙÂϤÛÌ·Ù·™ÙÔÓ ¶›Ó·Î· 1 Ê·›ÓÂÙ·È Ô ·ÚÈıÌfi˜ ÙˆÓ ·ÛıÂÓÒÓ

·Ó¿ ηÙËÁÔÚ›· ÎÚÈÙËÚ›ˆÓ, Û‡Ìʈӷ Ì ٷ ÔÔ›· ÔÈÁÈ·ÙÚÔ› Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ·Ú¤-ÂÌ„·Ó ÙÔ˘˜ ·ÛıÂÓ›˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔ-ÎÔÌ›Ô. ¶·Ú·¤ÌÊıËÎ·Ó Û˘ÓÔÏÈο 112 ·ÛıÂÓ›˜, 17(15,2%) ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ‰È·ÈÛÙÒıËΠfiÙÈ Â›¯·ÓÁÓˆÛÙfi ÌÂÙ·‚ÔÏÈÎfi ÓfiÛËÌ·. ∏ ÓÔËÙÈ΋ ηı˘ÛÙ¤ÚË-ÛË (49 ·ÛıÂÓ›˜) Î·È ÔÈ Â›ÌÔÓÔÈ Û·ÛÌÔ› (36 ·ÛıÂ-Ó›˜) ‹Ù·Ó Ù· Û˘ÓËı¤ÛÙÂÚ· Û˘ÌÙÒÌ·Ù· ‹ ¯·Ú·-ÎÙËÚÈÛÙÈο ÁÈ· Ù· ÔÔ›· ÔÈ ·ÛıÂÓ›˜ ·Ú·¤ÌÊıË-ηÓ. ∆· Û˘ÓËı¤ÛÙÂÚ· ·fi Ù· ÌË Ó¢ÚÔÏÔÁÈο Û˘-ÌÙÒÌ·Ù· ‹ ¯·Ú·ÎÙËÚÈÛÙÈο Ô˘ ¤ıÂÛ·Ó ÙËÓ ˘fi-ÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ‹Ù·Ó Ë ·‰È¢ÎÚ›ÓÈÛÙ˘·ÈÙÈÔÏÔÁ›·˜, ¤ˆ˜ ÙfiÙÂ, ηı˘ÛÙ¤ÚËÛË Ù˘ ·Ó¿Ù˘ÍË˜Î·È ÙÔ Â›ÌÔÓÔ ¤Î˙ÂÌ·. ∆· Û˘¯ÓfiÙÂÚ· ÌÂÙ·‚ÔÏÈοÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËÎ·Ó ‹Ù·Ó ÔÈ ÔÚÁ·ÓÈΤ˜ÔÍÂÔ˘Ú›Â˜. ¢È·ÁÓÒÛÙËÎ·Ó Û˘ÓÔÏÈο 8 ·ÛıÂÓ›˜ ÌÂÔÚÁ·ÓÈ΋ ÔÍÂÔ˘Ú›· (47%), 3 ·ÛıÂÓ›˜ Ì ÁÏ˘ÎÔÁÔ-ÓÈ¿ÛÂȘ (17,6%), 2 ·ÛıÂÓ›˜ ̠ϢÎÔ‰˘ÛÙÚÔÊ›·(11,7%), 2 ·ÛıÂÓ›˜ ÌÂ Ï˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù·(11,7%), 1 ·ÛıÂÓ‹˜ Ì ‰È·Ù·Ú·¯¤˜ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfiÙˆÓ ·ÌÈÓÔͤˆÓ (5,8%) Î·È 1 ·ÛıÂÓ‹˜ Ì ÌÈÙÔ¯ÔÓ-‰ÚÈÔ¿ıÂÈ· (5,8%). ∆· ÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËηÓÎ·È Ë ËÏÈΛ· ÙˆÓ ·ÛıÂÓÒÓ Ê·›ÓÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 2.

™˘˙‹ÙËÛË ∏ ·ÚÔ‡Û· ÈÏÔÙÈ΋ ÌÂϤÙË ‰ÂÓ ÛÙÂÚÂ›Ù·È ÌÂıÔ-

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MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·135

¶·È‰È·ÙÚÈ΋ 2003;66:133-139 Paediatriki 2003;66:133-139

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Û˘ÌÌÂÙ¯fiÓÙˆÓ ·ÛıÂÓÒÓ, Ô ÔÔ›Ô˜ ‰ÂÓ ·ÓÙÈÚÔ-ۈ‡ÂÈ ÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi Î·È ÙÔ ÌË ÛÙ·ıÌÈ-Ṳ̂ÓÔ ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ ·ÔÙÂÏÔ‡Ó ‰‡Ô ‚·ÛÈΤ˜·‰˘Ó·Ì›Â˜ Ù˘ ÌÂϤÙ˘, Ô˘ ı· Ú¤ÂÈ Ó· ÏËÊıÔ‡Ó˘’ fi„ÈÓ ÛÙË Û˘˙‹ÙËÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Ù˘.¶·Ú¿ ÙÔ˘˜ ˘¿Ú¯ÔÓÙ˜ ÂÚÈÔÚÈÛÌÔ‡˜ Ê·›ÓÂÙ·È fiÙÈÙ· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· ÛÙËÓ ∫Ú‹ÙË ‰ÂÓ Â›Ó·È Ùfi-ÛÔ Û¿ÓÈ·, ·ÊÔ‡ ÛÙÔ ‚Ú·¯‡ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô˘‰ÈÂÍ‹¯ıË ·˘Ù‹ Ë ÌÂϤÙË ÙÂÎÌËÚÈÒıËÎÂ Ë ‰È¿ÁÓˆÛËÛ 17 ·fi ÙÔ˘˜ 112 ·ÛıÂÓ›˜ Ô˘ ·Ú·¤ÌÊıËηÓ(15,2%) (¶›Ó·Î·˜ 2). ™Â 12 ·fi Ù· 17 ÓÔÛ‹Ì·Ù·Ô˘ ‰È·ÁÓÒÛıËÎ·Ó ‹Ù·Ó ‰˘Ó·Ù‹ Ë ıÂڷ¢ÙÈ΋ ·-ڤ̂·ÛË. ™Â 4 ·fi ÙÔ˘˜ 12 ·ÛıÂÓ›˜, fiÔ˘ ‹Ù·Ó‰˘Ó·Ù‹ Ë ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË, Ë ÓfiÛÔ˜ ‰È·-ÁÓÒÛıËΠ۠ÚÔ¯ˆÚË̤ӷ ‹‰Ë ÛÙ¿‰È· Î·È Û¯ÂÙÈ-ο ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ·. ™˘ÓÂÒ˜, Ë ‚Ô‹ıÂÈ· Ô˘ ¯Ô-ÚËÁ‹ıËΠ‹Ù·Ó ΢ڛˆ˜ Û˘Ìو̷ÙÈ΋ Î·È ÙÔ ·Ô-Ù¤ÏÂÛÌ· Ù˘ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ ÎÚ›ıËηӷÚΤ˜.

÷ڷÎÙËÚÈÛÙÈΤ˜ Â›Ó·È ÔÈ ÙÚÂȘ ÂÚÈÙÒÛÂȘ ÙˆÓÁÏ˘ÎÔÁÔÓÈ¿ÛÂˆÓ Ô˘ ‰È·ÁÓÒÛÙËηÓ. OÈ ÁÏ˘ÎÔÁÔ-ÓÈ¿ÛÂȘ, ·Ó Î·È Â›Ó·È Û¿ÓȘ ÎÏËÚÔÓÔÌÈΤ˜ ‰È·Ù·-Ú·¯¤˜, ·Ó·Ê¤ÚÔÓÙ·È Û¯ÂÙÈο Û˘¯ÓfiÙÂÚ· ÛÙËÓ ÂÏÏË-ÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›· (10-12). ª›· ·ÛıÂÓ‹˜ ËÏÈΛ·˜ 26ÂÙÒÓ, ¿Û¯Ô˘Û· ·fi ÁÏ˘ÎÔÁÔÓ›·ÛË π‚ ·ÚÔ˘Û›·˙Â,fiˆ˜ ·ÚÁfiÙÂÚ· ‰È·ÈÛÙÒıËÎÂ, ·fi ÌÈÎÚ‹ ËÏÈΛ·˘ÔÁÏ˘Î·ÈÌÈΤ˜ ÎÚ›ÛÂȘ ¯ˆÚ›˜ ÂÌÊ·Ó‹ ·ÈÙ›· Î·È ¯ˆ-Ú›˜ ‰È·ÁÓˆÛÙÈο Â˘Ú‹Ì·Ù· ·fi ÙÔÓ ÂοÛÙÔÙ ÎÏÈÓÈ-ÎÔÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô. OÈ ÁÔÓ›˜ Ù˘ ÂÓÛÙÈÎÙˆ-‰Ò˜ ¯ÔÚËÁÔ‡Û·Ó ·fi ÌfiÓÔÈ ÙÔ˘˜ Ôχ Û˘¯Ó¿ Á‡-Ì·Ù· ÏÔ‡ÛÈ· Û ˘‰·Ù¿ÓıڷΘ. §fiÁˆ Ù˘ ·Ó·Ú-ÎÔ‡˜ ıÂڷ›·˜, Ì ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘ Ë·ÛıÂÓ‹˜ ·ÚÔ˘Û›·Û ‚·ÚÈ¿ ÔÛÙÂÔfiÚˆÛË, ÎÔÏ›ÙÈ-‰· Î·È Â›¯Â ¯·ÌËÏfi ·Ó¿ÛÙËÌ·. ∞ÚÎÂÙ¿ Û˘¯Ó¿ ·-ÚÔ˘Û›·˙ ÏÔÈÌÒÍÂȘ, ·ÓÙÈÌÂÙˆÈ˙fiÙ·Ó Û˘Ìو̷ÙÈ-ο Î·È ÓÔÛËÏ¢fiÙ·Ó Ôχ Û˘¯Ó¿ Û ·È‰È·ÙÚÈΤ˜ÎÏÈÓÈΤ˜. ™ÙÔ ÈÛÙÔÚÈÎfi Ù˘ ·ÛıÂÓÔ‡˜ ·Ó·Ê¤ÚıËÎÂ,›Û˘, ·fiÂÈÚ· ·˘ÙÔÎÙÔÓ›·˜ ÛÙËÓ ÂÊË‚È΋ ËÏÈΛ·.øÛÙfiÛÔ, ·Ú’ fiÏÔ Ô˘ Ë ‰È¿ÁÓˆÛË Ù¤ıËΠۯÂÙÈο

·ÚÁ¿, ¯ÔÚËÁ‹ıËΠ·˘ÍËÙÈÎfi˜ ·ÈÌÔÔÈËÙÈÎfi˜ ·Ú¿-ÁÔÓÙ·˜ Î·È ÙÚÔÔÔÈ‹ıËΠηٿÏÏËÏ· Ë ‰È·ÈÙËÙÈ΋·ÁˆÁ‹ Ì ·Ú¿ÏÏËÏË „˘¯ÔÏÔÁÈ΋ Î·È ÔÈÎÔÓÔÌÈ΋˘ÔÛÙ‹ÚÈÍË Î·È ‚ÂÏÙ›ˆÛË Ù˘ ÔÛÙÂÔfiÚˆÛ˘ ÛÂÛËÌ·ÓÙÈÎfi ‚·ıÌfi. ∏ ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·Û ‡ÊÂÛËÙˆÓ ÂΉËÏÒÛÂˆÓ ·fi ÙÔ ÂÙÈÎfi Î·È ÔÈ ÏÔÈÌÒÍÂȘÂÚÈÔÚ›ÛÙËÎ·Ó ÛËÌ·ÓÙÈο, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ‚ÂÏ-ÙȈı› Ë ÔÈfiÙËÙ· Ù˘ ˙ˆ‹˜ Ù˘. OÈ ¿ÏϘ ‰‡Ô ÂÚÈ-ÙÒÛÂȘ ·ÛıÂÓÒÓ Ì ÁÏ˘ÎÔÁÔÓ›·ÛË ‰ÂÓ Î·Ù¤ÛÙˉ˘Ó·Ùfi Ó· ‚ÔËıËıÔ‡Ó ·Ó¿ÏÔÁ·. ∫·È ÔÈ ‰‡Ô ·ÛıÂ-Ó›˜, ÏfiÁˆ ÙˆÓ ÔÏÏ·ÏÒÓ ˘ÔÁÏ˘Î·ÈÌÈÎÒÓ ÎÚ›ÛÂ-ˆÓ ·fi ÙË ‚ÚÂÊÈ΋ ÙÔ˘˜ ËÏÈΛ·, ·ÚÔ˘Û›·˙·Ó ÌË·Ó·ÛÙÚ¤„È̘ ÂÁÎÂÊ·ÏÈΤ˜ ‚Ï¿‚˜ Î·È ÛÔ‚·Ú‹Ë·ÙÔ¿ıÂÈ· ·fi ÙËÓ ÂÓ·fiıÂÛË ÁÏ˘ÎÔÁfiÓÔ˘.

∏ ÈÔ Û˘¯Ó‹ ηÙËÁÔÚ›· ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓÔ˘ ‰È·ÁÓÒÛıËÎ·Ó ‚Ú¤ıËΠӷ Â›Ó·È ·˘Ù‹ ÙˆÓ ÔÚ-Á·ÓÈÎÒÓ ÔÍÂÔ˘ÚÈÒÓ. ¢È·ÁÓÒÛıËÎ·Ó Û˘ÓÔÏÈο 8 ·È-‰È¿. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ‚ÚÂÊÈ΋˜ ËÏÈΛ·˜ ‰È·-ÁÓÒÛıËÎ·Ó 4 ÂÚÈÙÒÛÂȘ, ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÓË-ȷ΋˜ 3 Î·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÊË‚È΋˜ ËÏÈΛ·˜1 ÂÚ›ÙˆÛË. ∆· Â˘Ú‹Ì·Ù· Â›Ó·È ·Ó¿ÏÔÁ· Ì ¿ÏψÓÂȉËÌÈÔÏÔÁÈÎÒÓ ÌÂÏÂÙÒÓ (13,14). ŒÓ·˜ ·ÛıÂÓ‹˜Ì ÌÂı˘ÏÌ·ÏÔÓÈ΋ ÔÍÂÔ˘Ú›· ·Â‚›ˆÛ ·Ú¿ ÙËÓ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË, ÂÓ̤ۈ ÁÂÓÈÎÂ˘Ì¤ÓˆÓ ÙÔÓÈÎÔÎÏÔÓÈÎÒÓ Û·ÛÌÒÓ Ì·ÎfiÏÔ˘ıË ÂÈÛÚfiÊËÛË, ÂÓÒ Ô ‰Â‡ÙÂÚÔ˜ ·ÛıÂÓ‹˜Ì ÌÂı˘ÏÌ·ÏÔÓÈ΋ ÔÍÂÔ˘Ú›·, Ì ÙËÓ Î·Ù¿ÏÏËÏË ıÂ-ڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ¤¯ÂÈ Û‹ÌÂÚ· Û¯ÂÙÈο ηϋÔÈfiÙËÙ· ˙ˆ‹˜. ¢‡Ô ·ÛıÂÓ›˜ Ì ‰È·Ù·Ú·¯¤˜ Ù˘ ‚-ÔÍ›‰ˆÛ˘ (MCAD Î·È LCHAD) ÂÈ‚›ˆÛ·Ó Ì ··-Ú·›ÙËÙË ÙÚÔÔÔ›ËÛË Ù˘ ‰È·ÈÙËÙÈ΋˜ ·ÁˆÁ‹˜.∂ӉȷʤÚÔ˘Û· ÎÚ›ÓÂÙ·È Ë ÂÚ›ÙˆÛË ÂÓfi˜ ·ÁÔÚÈÔ‡ËÏÈΛ·˜ 2,5 ÂÙÒÓ Ô˘ ‰È·ÈÛÙÒıËΠfiÙÈ ¤·Û¯Â ·fi·Ó¿ÚÎÂÈ· ‚ÈÔÙÈÓȉ¿Û˘. ∆Ô ·È‰› ‰ÂÓ ·ÚÔ˘Û›·˙ÂÙ· ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÁÓˆÚ›ÛÌ·Ù· Ù˘ ÓfiÛÔ˘(Û·ÛÌÔ›, ÂÍ¿ÓıËÌ·). ∆Ô ÌfiÓÔ Â‡ÚËÌ· ·fi ÙËÓ ÎÏÈ-ÓÈ΋ ÂÎÙ›ÌËÛË ‹Ù·Ó Ë ·ÚÔ˘Û›· ·˘ÙÈÛÙÈ΋˜ Û˘ÌÂ-ÚÈÊÔÚ¿˜. ∞fi fiÛÔ ÁÓˆÚ›˙Ô˘ÌÂ Â›Ó·È Ë ‰Â‡ÙÂÚË Â-Ú›ÙˆÛË ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· Ô˘ ‰È·ÁÈÁÓÒÛÎÂÙ·È·ÛıÂÓ‹˜ Ì ·Ó¿ÚÎÂÈ· ‚ÈÔÙÈÓȉ¿Û˘ Î·È ·˘ÙÈÛÙÈÎ‹Û˘ÌÂÚÈÊÔÚ¿ (15,16). O ·ÛıÂÓ‹˜ ·ÓÙ·ÔÎÚ›ıËÎÂÂÓÙ˘ˆÛȷο ÛÙË ¯ÔÚ‹ÁËÛË ‚ÈÔÙ›Ó˘ Î·È ÁÚ‹ÁÔÚ··Ó¤Ù˘ÍÂ Ê˘ÛÈÔÏÔÁÈ΋ ÎÔÈÓˆÓÈ΋ ÚÔÛ·ÚÌÔÁ‹.

™ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰È·ÁÓÒÛıËÎ·Ó Ï¢ÎÔ‰˘-ÛÙÚÔʛ˜ ·Ú·Û¯¤ıËΠÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘Ô-ÛÙ‹ÚÈÍË Î·È ÁÂÓÂÙÈ΋ Û˘Ì‚Ô˘Ï¢ÙÈ΋.

™Â ‰‡Ô ·ÛıÂÓ›˜ ‰È·ÁÓÒÛıËÎÂ Ï˘ÛÔÛÛˆÌȷ΋ÓfiÛÔ˜. O ÚÒÙÔ˜ ·ÛıÂÓ‹˜ ‹Ù·Ó ¤Ó· ÎÔÚ›ÙÛÈ ËÏÈΛ·˜3 ÂÙÒÓ Ì ·Ó¿ÚÎÂÈ· ·-Ì·ÓÓÔÛȉ¿Û˘. ¶ÚÔÁÂÓÓË-ÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ Ù˘ ÌËÙ¤Ú·˜ Ù˘ ·ÛıÂÓÔ‡˜, Ë ÔÔ›·‹‰Ë ΢ÔÊÔÚÔ‡Û ¤Ì‚Ú˘Ô ËÏÈΛ·˜ Ï›ÁˆÓ ‚‰ÔÌ¿-‰ˆÓ, η٤‰ÂÈÍ fiÙÈ ÙÔ ¤Ì‚Ú˘Ô ‰ÂÓ ¤·Û¯Â ·fi ÙËÓfiÛÔ. ∏ ‰Â‡ÙÂÚË ·ÛıÂÓ‹˜ Ì ÓfiÛÔ Ï˘ÛÔÛۈ̷ٛˆÓ

¶›Ó·Î·˜ 1. ™˘ÌÙÒÌ·Ù· Î·È ‰È·Ù·Ú·¯¤˜ Ô˘ ·ÍÈÔÏÔÁ‹ıËηÓ(·ÚÈıÌfi˜ ·ÛıÂÓÒÓ ·Ó¿ ηÙËÁÔÚ›·)

™˘ÌÙÒÌ·Ù·* ∞ÛıÂÓ›˜ (·ÚÈıÌfi˜)

¡ÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË 49ªË ÂÏÂÁ¯fiÌÂÓÔÈ Û·ÛÌÔ› 36∫·ı˘ÛÙ¤ÚËÛË Ù˘ ·Ó¿Ù˘Í˘ 18∂›ÌÔÓÔ ¤Î˙ÂÌ· 14¢È·Ù·Ú·¯¤˜ ÙÔ˘ ÏfiÁÔ˘ 9™˘ÌÙÒÌ·Ù· ¿ÛËÙ˘ ÂÁÎÂÊ·Ï›Ùȉ·˜ 8¶˘Ú·ÌȉÈ΋ Û˘Ó‰ÚÔÌ‹ 8∞˘ÙÈÛÙÈ΋ Û˘ÌÂÚÈÊÔÚ¿ 7™˘ÌÙÒÌ·Ù· ÂÚÈÊÂÚÈ΋˜ Ó¢ÚÔ¿ıÂÈ·˜ 5ÀÔÁÏ˘Î·ÈÌ›· 5

* 36 ·ÛıÂÓ›˜ ·ÚÔ˘Û›·˙·Ó ≥2 Û˘ÌÙÒÌ·Ù·

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·136

˘¤ÊÂÚ ·fi ÙËÓ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘Gaucher. ∏ ÓfiÛÔ˜ Gaucher Â›Ó·È ÙÔ Û˘¯ÓfiÙÂÚÔ ·fiÙ· Ï˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù· Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÂÁ¿-ÏË ÎÏÈÓÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ· (17). H ·ÛıÂÓ‹˜ Ì ÓfiÛÔGaucher ÛÙË ÌÂϤÙË ·˘Ù‹ ‰È·ÁÓÒÛıËΠ۠ÌÂÁ¿ÏËÛ¯ÂÙÈο ËÏÈΛ· Î·È ·Ú·¤ÌÊıËΠÛÙË ÌÔÓ¿‰· ÌÂ-Ù·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÏfiÁˆ Ù˘ ÛÔ‚·Ú‹˜ ηı˘ÛÙ¤-ÚËÛ˘ Ù˘ ·Ó¿Ù˘Í˘, ·fiÙÔÎÔ Ù˘ ̄ ÚfiÓÈ·˜ ÓfiÛÔ˘.¶¤Ú·Ó ÙˆÓ Ù˘ÈÎÒÓ ·ÈÌ·ÙÔÏÔÁÈÎÒÓ Î·È ÔÛÙÈÎÒÓ ·Ï-ÏÔÈÒÛÂˆÓ Ù˘ ÓfiÛÔ˘, ·ÚÔ˘Û›·˙ ÂÈϤÔÓ Â›ÌÔÓËÂÎ˙ÂÌ·ÙÔÂȉ‹ ‰ÂÚÌ·Ù›Ùȉ· ¿ÎÚˆÓ Î·È ÚÔÛÒÔ˘.¶·Ú’ fiÏÔ Ô˘ Û ·ÛıÂÓ›˜ Ì ¿ÏÏ· Ï˘ÛÔÛÛˆÌȷοÓÔÛ‹Ì·Ù· (fiˆ˜ ÔÈ Á·ÁÁÏÈÔÛȉÒÛÂȘ GM1) Ë ¤Îı˘-ÛË ÂÍ·ÓıËÌ¿ÙˆÓ ÂÚÈÁÚ¿ÊÂÙ·È ÛÙËÓ Ù˘È΋ ÎÏÈÓÈ΋ÂÈÎfiÓ· Ù˘ ÓfiÛÔ˘, ÛÙË ÓfiÛÔ Gaucher Ë Û˘ÌÌÂÙÔ¯‹ÙÔ˘ ‰¤ÚÌ·ÙÔ˜ ı· Ú¤ÂÈ Ó· ıˆÚËı› ¿Ù˘Ë Ê·ÈÓÔ-Ù˘È΋ ÂΉ‹ÏˆÛË Î·È Ì¤¯ÚȘ ·Ô‰Â›Íˆ˜ ÙÔ˘ ÂÓ·-ÓÙ›Ô˘ ‰ÂÓ ı· Ú¤ÂÈ Ó· Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙË ÓfiÛÔ. ∏Û˘ÛÛÒÚ¢ÛË ÙÔ˘ ÁÏ˘ÎÔÛÂÚ‚ÚÔÛȉ›Ô˘ ÛÙÔÓ Ì˘ÂÏfiÔ‰‹ÁËÛ Û ·Ó·ÈÌ›·, Ï¢ÎÔÂÓ›· Î·È ıÚÔÌ‚Ô΢ÙÙ·-ÚÔÂÓ›·. §fiÁˆ Ù˘ Û˘ÌÌÂÙÔ¯‹˜ ÙÔ˘ Ì˘ÂÏÔ‡ Ì ·-ÎfiÏÔ˘ıË ·Ó΢ÙÙ·ÚÔÂÓ›· ¯ˆÚ›˜ ÚÔÛ‚ÔÏ‹ ÙÔ˘ ÎÂ-ÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, Ë ·ÛıÂÓ‹˜ Ù¤ıËÎÂÛ ÂÓ˙˘ÌÈ΋ ıÂڷ›· ˘ÔηٿÛÙ·Û˘ (18,19).

ŒÓ·˜ ·ÛıÂÓ‹˜ Ì ÓfiÛÔ ÔÛÌ‹˜ Ô‡ÚˆÓ ÛÊÂÓ‰¿-ÌÔ˘ (Maple syrup disease) ‰È·ÁÓÒÛıËΠ¤ÁηÈÚ·Û ÌÈÎÚ‹ ËÏÈΛ· Î·È Ì ÙËÓ Î·Ù¿ÏÏËÏË ıÂڷ¢ÙÈÎ‹Î·È ‰È·ÈÙËÙÈ΋ ·ÁˆÁ‹ ·ÚÔ˘ÛÈ¿˙ÂÈ Û‹ÌÂÚ· Ê˘ÛÈÔ-

ÏÔÁÈ΋ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍË. ™ÙÔÓ ·ÛıÂÓ‹ Ô˘ ‰È·ÁÓÒÛıËΠÌÈÙÔ¯ÔÓ‰ÚÈÔ¿-

ıÂÈ· ‰ÂÓ Î·Ù¤ÛÙË ‰˘Ó·Ù‹ Ë ÂÊ·ÚÌÔÁ‹ Û˘Ì‚Ô˘Ï¢-ÙÈ΋˜ ÁÂÓÂÙÈ΋˜, ÏfiÁˆ ÙÔ˘ ÔχÏÔÎÔ˘ ÙÚfiÔ˘ ÌÂÙÔÓ ÔÔ›Ô ÎÏËÚÔÓÔÌÔ‡ÓÙ·È ÔÈ ÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂȘ(20,21). ∏ ·ÓÙÈÌÂÙÒÈÛË ‹Ù·Ó Û˘Ìو̷ÙÈ΋, ÂÓÒÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ·Ú·Û¯¤ıËΠοı „˘¯ÔÏÔÁÈÎ‹Î·È ÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË. ™˘Ìو̷ÙÈ΋ ıÂÚ·-›·, „˘¯ÔÏÔÁÈ΋ Î·È ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹-ÚÈÍË ·Ú·Û¯¤ıËΠ۠fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂ-ϤÙ˘, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ·Ó Ù¤ıËΠ‹ fi¯È Ë ‰È¿-ÁÓˆÛË ÁÓˆÛÙÔ‡ ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜.

™Â fiÏË ·˘Ù‹ ÙËÓ ÚÔÛ¿ıÂÈ·, Ë Û˘Ì‚ÔÏ‹ ÙˆÓ È·-ÙÚÒÓ Ù˘ ÁÂÓÈ΋˜ È·ÙÚÈ΋˜ Î·È ÙˆÓ ·È‰È¿ÙÚˆÓ Ô˘ÂÚÁ¿˙ÔÓÙ·È ÛÙ· ΤÓÙÚ· ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜˘Á›·˜ ‹Ù·Ó Ôχ ÌÂÁ¿ÏË. ÷ڷÎÙËÚÈÛÙÈο ·Ó·Ê¤-ÚÂÙ·È fiÙÈ Ù· ÚÒÙ· 2 ¯ÚfiÓÈ· ÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ ÌÔÓ¿-‰·˜ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ·Ú·¤ÌÊıËÎ·Ó ÛÙÔ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ÙÔ˘ ∏Ú·ÎÏ›Ԣ ÌfiÓÔ70 ·ÛıÂÓ›˜, ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ÌfiÓÔ 21 (30%) ‹Ù·Ó·fi ÙËÓ ‡·ÈıÚÔ. ™ÙȘ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘∫Ú‹Ù˘, ÌÂÚÈΤ˜ ·fi ÙȘ Ôԛ˜ Â›Ó·È ¿ÎÚˆ˜ ·Ô-ÌÔӈ̤Ó˜, ÂÈÎÚ·ÙÔ‡Ó È‰È¿˙Ô˘Û˜ ÎÔÈÓˆÓÈΤ˜ ηÈÔÏÈÙÈÛÌÈΤ˜ Û˘Óı‹Î˜ Î·È Ë Â·Ê‹ Ì ÙÔÓ È·ÙÚfi ›-Ó·È Û˘¯Ó¿ ÂÍ·ÈÚÂÙÈο ‰‡ÛÎÔÏË. ™Â ÔÏϤ˜ ÔÈÎÔÁ¤-ÓÂȘ ıˆÚÂ›Ù·È "ÛÙ›ÁÌ·” Ë ‡·ÚÍË ÂÓfi˜ ·ÙfiÌÔ˘ ÌÂÓÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË ‹ ¿ÏÏ· Û˘ÌÙÒÌ·Ù· ·fi ÙÔÓ¢ÚÈÎfi Û‡ÛÙËÌ·, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ˘¿Ú¯Ô˘Ó

¶·È‰È·ÙÚÈ΋ 2003;66:133-139 Paediatriki 2003;66:133-139

137

¶›Ó·Î·˜ 2. ∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ ·Ó¿ ηÙËÁÔÚ›· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÁÈ· ÙÔ ÔÔ›Ô ÂȂ‚·ÈÒıËÎÂ Ë ‰È¿ÁÓˆÛË. OÈ ÔÚÁ·ÓÈΤ˜ÔÍ˘Ô˘Ú›Â˜ ‹Ù·Ó Ù· Û˘¯ÓfiÙÂÚ· ·fi Ù· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËηÓ

ªÂÙ·‚ÔÏÈÎfi ÓfiÛËÌ· ∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ Ô˘ ‰È·ÁÓÒÛıËÎ·Ó (%)

OÚÁ·ÓÈ΋ Ô͢Ԣڛ· 8 (47%)ªÂı˘ÏÌ·ÏÔÓÈ΋ Ô͢Ԣڛ· (6 ÌËÓÒÓ)ªÂı˘ÏÌ·ÏÔÓÈ΋ Ô͢Ԣڛ· (10 ÌËÓÒÓ)LCHAD (10 ÌËÓÒÓ)MCAD (11 ÌËÓÒÓ)∞Ó¿ÚÎÂÈ· ‚ÈÔÙÈÓȉ¿Û˘ (2,5 ÂÙÒÓ)ÀÂÚÔÍ·ÏÔ˘Ú›· (3 ÂÙÒÓ)2-ÔÍÔÁÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ· (5 ÂÙÒÓ)°ÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ· Ù‡Ô˘ I (13 ÂÙÒÓ)

°Ï˘ÎÔÁÔÓÈ¿ÛÂȘ 3 (17,6%)°Ï˘ÎÔÁÔÓ›·ÛË Ù‡Ô˘ πa (15 ÂÙÒÓ)°Ï˘ÎÔÁÔÓ›·ÛË Ù‡Ô˘ III (21 ÂÙÒÓ)°Ï˘ÎÔÁÔÓ›·ÛË Ù‡Ô˘ Ib (26 ÂÙÒÓ)

§Â˘ÎÔ‰˘ÛÙÚÔʛ˜ 2 (11,7%)¡fiÛÔ˜ Canavan (12 ÌËÓÒÓ)º˘ÏÔÛ‡Ó‰ÂÙË ·‰ÚÂÓÔÏ¢ÎÔ‰˘ÛÙÚÔÊ›· (8 ÂÙÒÓ)

§˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù· 2 (11,7%)∞Ó¿ÚÎÂÈ· ·-Ì·ÓÓÔÛȉ¿Û˘ (3 ÂÙÒÓ)¡fiÛÔ˜ Gaucher Ù‡Ô˘ I (30 ÂÙÒÓ)

¢È·Ù·Ú·¯¤˜ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ·ÌÈÓÔͤˆÓ 1 (5,8%)¡fiÛÔ˜ ÔÛÌ‹˜ Ô‡ÚˆÓ ÛÊÂÓ‰¿ÌÔ˘ (Maple syrup disease) (2 ÌËÓÒÓ)

ªÈÙÔ¯ÔӉȷΤ˜ ÂÁÎÂÊ·ÏÔ¿ıÂȘ 1 (5,8%)™˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ π Î·È πππ (2 ÂÙÒÓ)

™‡ÓÔÏÔ ·ÛıÂÓÒÓ Ô˘ ‰È·ÁÓÒÛıËÎ·Ó 17

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‰˘ÛÎÔϛ˜ ÛÙËÓ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ·ÔηٿÛÙ·-ÛË fiÏˆÓ ÙˆÓ ÌÂÏÒÓ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜ (Á¿ÌÔ˜, ‡ÚÂ-ÛË ÂÚÁ·Û›·˜). ∏ ·ÙÂÏ‹˜ Î·È ÂÛÊ·Ï̤ÓË Û˘¯Ó¿ ·ÓÙ›-ÏË„Ë Î·È ÂÓË̤ڈÛË ÙÔ˘ ÏËı˘ÛÌÔ‡ Ù˘ ÂÚÈʤ-ÚÂÈ·˜ ÁÈ· Ù· ÓÔÛ‹Ì·Ù· ·˘Ù¿, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ·ÙÂÏ‹ Âη›‰Â˘ÛË ÙˆÓ ÁÈ·ÙÚÒÓ, ηıÈÛÙÔ‡Ó ÙȘ ‰È·-ÛÙ¿ÛÂȘ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜ ·ÎfiÌ· ÌÂÁ·Ï‡ÙÂÚ˜.

ªÂ ÙË Û˘ÌÌÂÙÔ¯‹ ÛÙË ÌÂϤÙË ·˘Ù‹, ÔÈ ÁÈ·ÙÚÔ›Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÂÓËÌÂÚÒıË-Î·Ó Î·È Âηȉ‡ÙËÎ·Ó Û¯ÂÙÈο Ì ÙË ‰È¿ÁÓˆÛË Î·ÈÙȘ ‰˘Ó·ÙfiÙËÙ˜ ·ÓÙÈÌÂÙÒÈÛ˘ Î·È ÁÂÓÂÙÈ΋˜ Û˘Ì-‚Ô˘Ï¢ÙÈ΋˜ ÛÙ· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∞˘ÙÔ› Ì ÙËÛÂÈÚ¿ ÙÔ˘˜, ÏfiÁˆ Ù˘ ηχÙÂÚ˘ ·ʋ˜ Ô˘¤¯Ô˘Ó Ì ÙÔ˘˜ ηÙÔ›ÎÔ˘˜ ÙˆÓ ·ÁÚÔÙÈÎÒÓ ÂÚÈÔ¯ÒÓ,ÌfiÚÂÛ·Ó Ó· ¢·ÈÛıËÙÔÔÈ‹ÛÔ˘Ó ÙÔÓ ÏËı˘ÛÌfiÙ˘ ˘·›ıÚÔ˘ ÁÈ· ÙËÓ ÂÈÙ·ÎÙÈ΋ ·Ó¿ÁÎË ÂϤÁ¯Ô˘,fiÔ˘ Ù¤ıËΠ˘fiÓÔÈ· Ù¤ÙÔÈÔ˘ ÓÔÛ‹Ì·ÙÔ˜. OÈ ÁÈ·-ÙÚÔ› Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ·Ú¤Â-Ì·Ó ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹-Ì·ÙÔ˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›-Ô˘. ªÂ ÙË Û˘ÓÂÚÁ·Û›· ÙˆÓ ÓÔÛÔÎÔÌÂÈ·ÎÒÓ È·ÙÚÒÓÎ·È ÙˆÓ È·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›-·˜ ÙÂÎÌËÚÈÒıËΠ‰È¿ÁÓˆÛË ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·-ÙÔ˜ Û 17 ·fi 112 ·ÛıÂÓ›˜ Ô˘ ·Ú·¤ÌÊıËηÓ.ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÛÙË ªÔÓ¿‰·ªÂÙ·‚ÔÏÈÎÒÓ ¡ÔÛËÌ¿ÙˆÓ Î·È Û fiÏÔ˘˜ ¤¯ÂÈ ·Ú·-Û¯Âı› οı ‰˘Ó·Ù‹ ‚Ô‹ıÂÈ·. ™ÙÔÓ ÂÓÙÔÈÛÌfi ÙˆÓ“‡ÔÙˆÓ” ·ÙfiÌˆÓ ‚Ô‹ıËÛ ȉȷ›ÙÂÚ· ÙÔ ÂÚˆÙËÌ·-ÙÔÏfiÁÈÔ Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ. ∆Ô ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ·˘Ùfi, ·Ó Î·È ‰ÂÓ Â›Ó·È Ï‹Ú˜, ÌÔÚ› Ó· ıˆÚËı›ηٿÏÏËÏÔ ÁÈ· ÙÔ˘˜ ÁÈ·ÙÚÔ‡˜ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÏfiÁˆ ÙÔ˘ fiÙÈ Â›Ó·È Û‡ÓÙÔÌÔ, ·ÏfiÎ·È ·ÚÔ˘ÛÈ¿˙ÂÈ ˘„ËÏ‹ ¢·ÈÛıËÛ›·, fiˆ˜ ·Ô‰Â›-¯ıËΠ·fi ÙÔ Û¯ÂÙÈο ˘„ËÏfi ÔÛÔÛÙfi ‰È·ÁÓÒÛˆÓÛÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ú·¤ÌÊıËηÓ.

™˘ÌÂÚ·ÛÌ·ÙÈο, Ë Û˘Ì‚ÔÏ‹ Ù˘ Û˘ÓÂÚÁ·Û›·˜ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜Î·È ÙˆÓ ÓÔÛÔÎÔÌÂÈ·ÎÒÓ ÁÈ·ÙÚÒÓ Ê·›ÓÂÙ·È ÛËÌ·ÓÙÈ-΋ ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË, ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒ-ÈÛË, ÁÂÓÂÙÈ΋ Û˘Ì‚Ô˘Ï¢ÙÈ΋ Î·È ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔ-ÌÈ΋ ˘ÔÛÙ‹ÚÈÍË ·ÛıÂÓÒÓ Î·È ÔÈÎÔÁÂÓÂÈÒÓ Ì ÌÂÙ·-‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∏ ÚÔÛÂÎÙÈ΋ ·ÍÈÔÏfiÁËÛË ÂÓfi˜·ÚÈıÌÔ‡ ÎÏÈÓÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ‹ Û˘Ìو̿وÓÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È ¤Ì-ÌÂÛ· ÛÙËÓ ¤ÁηÈÚË ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË, fiÔ˘·˘Ù‹ Â›Ó·È Û‹ÌÂÚ· ÂÊÈÎÙ‹. ŸÌˆ˜, ·ÎfiÌË Î·È fiÙ·Ó Ôȉ˘Ó·ÙfiÙËÙ˜ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ Â›Ó·È Â-ÚÈÔÚÈṲ̂Ó˜, Â›Ó·È ÛËÌ·ÓÙÈ΋ Î·È ÂÈÙ·ÎÙÈ΋ Ë ·-ÚÔ¯‹ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋˜ ˘ÔÛÙ‹ÚÈ͢ Î·È ÁÂÓÂ-ÙÈ΋˜ Û˘Ì‚Ô˘Ï¢ÙÈ΋˜.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn

errors of metabolism in British Columbia, 1969-1996.

Pediatrics 2000;105:e10. 2. Zakiah I, Ashikin YN, Aisiah SM, Ismail HI. Inborn errors of

metabolic diseases in Malaysia: a preliminary report ofmaple syrup urine diseases for 1993. Southeast Asian JTrop Med Pubic Health 1995;26 (Suppl 1):134-136.

3. Kaur M, Das GP, Verma IC. Inborn errors of amino acidmetabolism in north India. J Inherit Metab Dis 1994;17:230-233.

4. Widhalm K. 25 years Austrian screening program for inbornerrors of metabolism at the Vienna University. Wien KlinWochenschr 1992;104:510-513.

5. Toone JR, Applegarth DA, Vallance HD, Wilson RD. Earlyamniocentesis for biochemical genetic prenatal diagnosis.Lancet 1998;351:1207-1208.

6. Mathieu M. Prenatal diagnosis of genetic diseases inFrance. Ann Pharm Fr 1999;57:380-384.

7. ∂˘·ÁÁÂÏ›Ô˘ ∞, °È·ÓÓ·ÎÔÔ‡ÏÔ˘ Ã, ™Ì˘Ú¿ÎȘ ™. ¢È·ÁÓˆÛÙÈ-΋ ÚÔۤϷÛË ÙˆÓ Ó¢ÚÔÂÎÊ˘ÏÈÛÙÈÎÒÓ Î·È ÌÂÙ·‚ÔÏÈÎÒÓÓÔÛËÌ¿ÙˆÓ ÙˆÓ ·È‰ÈÒÓ. ¶·È‰È·ÙÚÈ΋ 1995;58:456-461.

8. Snyderman SE. Clinical aspects of disorders of the ureacycle. Pediatrics 1981;68:284-289.

9. Rezvani I, Rosenblatt D. Metabolic diseases. An approach toinborn errors. In: Saunders Company, eds. Nelson Textbookof Pediatrics. 16th ed. Philadelphia, Pensylvania; 2000. p.343-344.

10. ¢ÚÔÁοÚË ∂, ª·ÓˆÏ¿ÎË ¡, ¡·ÎÔÔ‡ÏÔ˘ §. °Ï˘ÎÔÁÔÓ›·ÛËÙ‡Ô˘ π· (ÂÌÂÈÚ›· 19 ÂÚÈÙÒÛÂˆÓ Û ·È‰È¿). π·ÙÚÈ΋1992;621:481-485.

11. ∂ÌÔÚÈ¿‰Ô˘ ª, ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘ ¶, ∞ÔÛÙÔÏ›-‰Ô˘ ∫, ∫·Úη‚¤Ï·˜ °, ¢ÚÔ˘ÛÈÒÙÔ˘ ∞, µ·ÚÏ¿Ì˘ °. ¶ÂÚÈ-ÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ‚ÚÂÊÈÎÔ‡ Ù‡Ô˘ ÁÏ˘ÎÔÁÔÓ›·Û˘ Ù‡Ô˘ππ. ¡fiÛÔ˜ Pompe. ¶·È‰È·ÙÚÈ΋ 1998;61:408-413.

12. ª¿ÓÙ˙ÈÔ˘ £, §È·ÎÔÔ‡ÏÔ˘ £, ¢ÚÔÁοÚË ∂, ∞ı·Ó·Û¿ÎË ∫,∫·Ú·ÌԇϷ ∞, ∫·ÙÙ¿Ì˘ Ã. ∞ÒÙÂÚ˜ ÂÈÏÔΤ˜ ÁÏ˘ÎÔ-ÁÔÓ›·Û˘ Ù‡Ô˘ π·. ¢ÂÏÙ ∞’ ¶·È‰È·ÙÚ ¶·Ó ∞ıËÓÒÓ1998;45:166-171.

13. Rashed M, Ozand PT, al Aqeel A, Gascon GG. Experienceof King Faisal Specialist Hospital and Research Center withSaudi organic acid disorders. Brain Dev 1994;16 (Suppl):1-6.

14. Lehnert W. Long-term results of selective screening forinborn errors of metabolism. Eur J Pediatr 1994;153 (Suppl1):S9-13.

15. Norrgard KJ, Pomponio RJ, Hymes J, Wolf B. Mutationscausing profound biotinidase deficiency in childrenascertained by newborn screening in the United Statesoccur at different frequencies than in symptomatic children.Pediatr Res 1999;46:20-27.

16. Colamaria V, Burlina AB, Gaburro D, Pajno-Ferrara F,Saudubray JM, Merino RG et al. Biotin-responsive infantileencephalpathy: EEG-polygraphic study of a case. Epilepsia1989;30:573-578.

17. Moraitou M, van Weely S, Verhoek M, Aerts J, Dimitriou E,Michelakakis H. The facile detection of 1505G�A inGaucher patients with different phenotypes. BiochimBiophys Acta 2001;1536:97-102.

18. Ida H, Rennert OM, Kato S, Ueda T, Oishi K, Maekawa K etal. Severe skeletal complications in Japanese patients with

¶·È‰È·ÙÚÈ΋ 2003;66:133-139 Paediatriki 2003;66:133-139

138

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·138

¶·È‰È·ÙÚÈ΋ 2003;66:133-139 Paediatriki 2003;66:133-139

139

type I Gaucher disease. J Inherit Metab Dis 1999;22:63-73. 19. Maaswinkel-Mooij P, Hollak C, van Eysden-Plaisier M, Prins

M, Aerts H, Poll R. The natural course of Gaucher disease inThe Netherlands: implications for monitoring of diseasemanifestations. J Inherit Metab Dis 2000;23:77-82.

20. Howell N. Human mitochondrial diseases: answeringquestions and questioning answers. Int Rev Cytol1999;186:49-116.

21. Santorelli FM, Tanji K, Shanske S, Krishna S, Schmidt RE,Greenwood RS et al. The mitochondrial DNA A8344Gmutation in Leigh syndrome revealed by analysis in paraffin-

embedded sections: revisiting the past. Ann Neurol1998;44:962-964.

HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-03-2002HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 20-12-2002

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ªÈ¯·ËÏ›‰Ô˘ ∂ϤÓ˶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋¶ÂÚÈÊÂÚÂÈ·Îfi ¶·ÓÂÈÛÙËÌÈ·Îfi °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô∏Ú¿ÎÏÂÈÔ, ∫Ú‹ÙË

™ÎÔfi˜: ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Ù˘ ·Ó¿Ù˘Í˘ ηÈÙ˘ ‰È·ÙÚÔÊÈ΋˜ ηٿÛÙ·Û˘ ·È‰ÈÒÓ Ì ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜‹Ù·Ó Ó· ‰ÈÂÚ¢ÓËı› Â¿Ó Û˘ÁÎÂÎÚÈ̤Ó˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜,‰›·ÈÙ˜ ÂÚÈÔÚÈÛÌÔ‡ ‹ ¿ÏϘ ·Ú¿ÌÂÙÚÔÈ Û¯ÂÙÈ˙fiÌÂÓ˜ Ì ÙȘÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ ÂËÚ¿˙Ô˘Ó ÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ·È‰ÈÒÓ.ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: °È· ÙÔÓ Î·ıÔÚÈÛÌfi Èı·ÓÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ·Ó¿Ù˘Í˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÌÂÙÚ‹ÛÂȘ ‡„Ô˘˜, ‚¿ÚÔ˘˜ ηȉ›ÎÙË Ì¿˙·˜ ÛÒÌ·ÙÔ˜. OÈ ÂÎÙÈÌ‹ÛÂȘ ÁÈ· ÙËÓ ÂÓ¤ÚÁÂÈ· Î·È Ù·ıÚÂÙÈο Û˘ÛÙ·ÙÈο ‚·Û›ÛÙËÎ·Ó Û ÙÚÈ‹ÌÂÚ· ËÌÂÚÔÏfiÁÈ· η-Ù·ÁÚ·Ê‹˜ ÙÚÔʛ̈Ó. ŒÓ· ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂÁÈ· ÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÙÚÔÊÈÎÒÓ ·ÏÏÂÚÁÈÒÓ Î·È¿ÏÏˆÓ ÌÂÙ·‚ÏËÙÒÓ. ™Â ·˘Ù‹ ÙËÓ ÚÔÔÙÈ΋, ‰È·ÛÙ·˘ÚÔ‡ÌÂÓËÌÂϤÙË Û˘ÌÌÂÙ›¯·Ó 99 ·È‰È¿ Ì ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ (·ÛıÂ-Ó›˜) Ì ̤ÛË ËÏÈΛ· Ù· 3,7±2,3 ¤ÙË Î·È 99 ·È‰È¿ ¯ˆÚ›˜ ÙÚÔ-ÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ (‰Â›ÁÌ· ·Ó·ÊÔÚ¿˜) Ì ̤ÛË ËÏÈΛ· Ù·4,1±2,4 ¤ÙË. ∏ ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË ‰ÈÂÍ‹¯ıË Ì ÙÔ Cochran-Mantel-Haeszel Statistics, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÁÂÓÈ΋ Û˘Û¯¤ÙÈÛËÎ·È Fisher Exact Test. ∞ÔÙÂϤÛÌ·Ù·: ∆· ·È‰È¿ Ì ‰‡Ô ‹ ÂÚÈÛÛfiÙÂÚ˜ ÙÚÔÊÈΤ˜·ÏÏÂÚÁ›Â˜ ›¯·Ó ¯·ÌËÏfiÙÂÚÔ ·Ó¿ÛÙËÌ·, Ì ÎÚÈÙ‹ÚÈÔ ÙȘ η-̇Ϙ ‡„Ô˘˜-ËÏÈΛ·˜, Û ۯ¤ÛË Ì ÂΛӷ Ì ̛· ÙÚÔÊÈ΋ ·Ï-ÏÂÚÁ›· (p<0,05). ¶ÂÚÈÛÛfiÙÂÚÔ ·fi ÙÔ 2,5% ÙˆÓ ·È‰ÈÒÓ Î·ÈÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ηٷӿψÓ ÏÈÁfiÙÂÚÔ ·fi 6,7% Ù˘ ËÌÂÚ‹-ÛÈ·˜ Û˘ÓÈÛÙÒÌÂÓ˘ ÔÛfiÙËÙ·˜ ÁÈ· ÙÔ ·Û‚¤ÛÙÈÔ, ÙË ‚ÈÙ·Ì›ÓË DÎ·È ÙË ‚ÈÙ·Ì›ÓË ∂. ¶ÂÚÈÛÛfiÙÂÚ· ·È‰È¿ Ì ·ÏÏÂÚÁ›· ÛÙÔ Á¿Ï··ÁÂÏ¿‰·˜ ‹ ÔÏϷϤ˜ ·ÏÏÂÚÁ›Â˜ Î·Ù·Ó¿ÏˆÓ·Ó ÏÈÁfiÙÂÚÔ·Û‚¤ÛÙÈÔ ·fi ÙËÓ ÂȉÈ΋ Û˘ÓÈÛÙÒÌÂÓË ÔÛfiÙËÙ· ÁÈ· ÙËÓ ËÏÈΛ·

Î·È ÙÔ Ê‡ÏÔ, Û˘ÁÎÚÈÓfiÌÂÓ· Ì ·È‰È¿ ¯ˆÚ›˜ ·ÏÏÂÚÁ›· ÛÙÔ Á¿-Ï· ·ÁÂÏ¿‰·˜ ηÈ/‹ Ì›· ÙÚÔÊÈ΋ ·ÏÏÂÚÁ›·. ∏ Èı·ÓfiÙËÙ· ÌÈ-ÎÚfiÙÂÚ˘ ·fi ÙË Û˘ÓÈÛÙÒÌÂÓË ÚfiÛÏ˄˘ ·Û‚ÂÛÙ›Ô˘ Î·È ‚È-Ù·Ì›Ó˘ D Û ·È‰È¿ Ì ÙÚÔÊÈ΋ ·ÏÏÂÚÁ›· ‹Ù·Ó ÏÈÁfiÙÂÚË, ·Ó ÙԷȉ› ÂÏ¿Ì‚·Ó ‰È·ÙÚÔÊÈΤ˜ Û˘Ì‚Ô˘Ï¤˜ (p<0,05) ‹ ηٷӿ-ψÓ ¤Ó· ·ÛʷϤ˜ ‚ÚÂÊÈÎfi/ÓÂÔÁÓÈÎfi ˘ÔηٿÛÙ·ÙÔ ‹ ˘Ôη-Ù¿ÛÙ·ÙÔ ÛfiÁÈ·˜. ™˘ÌÂÚ¿ÛÌ·Ù·: ¶·È‰È¿ Ì ‰È·ÁÓˆṲ̂Ó˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜¯ÚÂÈ¿˙ÔÓÙ·È ÂÙ‹ÛÈ· ‰È·ÙÚÔÊÈ΋ ·ÍÈÔÏfiÁËÛË ÁÈ· ÙËÓ ÚfiÏË„ËÚÔ‚ÏËÌ¿ÙˆÓ ·Ó¿Ù˘Í˘ ‹ ·Ó·ÚÎÔ‡˜ ÚfiÛÏ˄˘ ıÚÂÙÈ-ÎÒÓ Û˘ÛÙ·ÙÈÎÒÓ. ∆· ·È‰È¿ Ì ·ÏÏÂÚÁ›· ÛÙÔ Á¿Ï· ‹ ÔÏÏ·-Ϥ˜ ·ÏÏÂÚÁÈΤ˜ ·ÓÙȉڿÛÂȘ Â›Ó·È Û ÌÂÁ·Ï‡ÙÂÚÔ Î›Ó‰˘ÓÔ. ∏‰È·ÙÚÔÊÈ΋ Âη›‰Â˘ÛË Â›Ó·È ··Ú·›ÙËÙË ÁÈ· ÙËÓ ·ÔÊ˘Á‹fiÏˆÓ ÙˆÓ ÌÔÚÊÒÓ ÙÔ˘ ·ÏÏÂÚÁÈÔÁfiÓÔ˘ Î·È ÙËÓ ÂÓۈ̿وÛËÂÓ·ÏÏ·ÎÙÈÎÒÓ ıÚÂÙÈÎÒÓ ÙÚÔÊÒÓ. O ÏËı˘ÛÌfi˜ ·˘Ùfi˜ ı·ÌÔÚÔ‡Û ӷ ˆÊÂÏËı› ·fi ÙËÓ ·Ó¿Ù˘ÍË Î·È ÂÎÙ›ÌËÛË ÂÓfi˜ÎÏÈÓÈÎÔ‡ ‰È·ÙÚÔÊÈÎÔ‡ ıÂڷ¢ÙÈÎÔ‡ ÚˆÙÔÎfiÏÏÔ˘.

OÈ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ ÛÙ· ·È‰È¿ ÂËÚ¿˙Ô˘Ó ÙË ‰È·ÙÚÔÊÈ΋ ÚfiÛÏË„Ë Î·È ·Ó¿Ù˘ÍË1

¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›·

1Christie L, Hine RJ, Parker JG, Burks W Food allergies in children affect nutrient intake andgrowth J Am Diet Assoc 2002;102:1648-1651

∞ÈÌÈÏ›· µ·ÛÈÏÔÔ‡ÏÔ˘

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·139

¶·È‰È·ÙÚÈ΋ 2003;66:89-96 Paediatriki 2003;66:89-96

89

∏ ȉÈÔ·ı‹˜ ¤ÏÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ οو ·fi ÙÔ Ú›ÛÌ· Ó¤ˆÓ ÂÚ¢ÓËÙÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ ª.™. §·Ú›Ô˘, §. ™Ù·ÌÔÁÈ¿ÓÓÔ˘

Idiopathic growth hormone deficiency in the light of new research data M.S. Lariou, L. Stamoyannou

∞¡∞™∫O¶∏™∏ REVIEW ARTICLE

∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·

1st Pediatric Clinic, “P. & A. Kyriakou” Children’s Hospital, Athens

∂ÈÛ·ÁˆÁ‹∏ ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growth

hormone deficiency) Â›Ó·È Ì›· ‰È·Ù·Ú·¯‹ Ô˘ ÂÌ-Ê·Ó›˙ÂÙ·È ·ÁÎÔÛÌ›ˆ˜ ÛÂ Û˘¯ÓfiÙËÙ· 1:4000-10000

ÁÂÓÓ‹ÛÂȘ (1-3). ªfiÓÔ ÙÔ 20% ÙˆÓ ÂÚÈÙÒÛˆÓÔÊ›ÏÂÙ·È Û οÔÈÔ ÔÚÁ·ÓÈÎfi ·›ÙÈÔ (.¯. ÙÚ·‡Ì·,fiÁÎÔ ‹ Ïԛ̈ÍË), ÂÓÒ ÛÙȘ ˘fiÏÔȘ ÂÚÈÙÒÛÂÈ˜Ë ·ÈÙÈÔÏÔÁ›· Â›Ó·È ¿ÁÓˆÛÙË (Idiopathic) (4,5). ÕÚ·,

�¶ÂÚ›ÏË„Ë: À¿Ú¯Ô˘Ó ÌÂÚÈο ÌË ÔÚÁ·ÓÈο ·›ÙÈ·Ù˘ ·Ó¿ÚÎÂÈ·˜ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Ô˘ ÌÔ-ÚÔ‡Ó Ó· ·Ô‰ÔıÔ‡Ó Û ÁÂÓÂÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘¿ÍÔÓ· ˘Ôı·Ï¿ÌÔ˘-˘fiÊ˘Û˘. ¶ÚfiÛÊ·Ù˜ ÌÂϤ-Ù˜ ¤ÙÚ„·Ó ÙËÓ Ù·˘ÙÔÔ›ËÛË ÂÓfi˜ ·ÚÈıÌÔ‡ ÁÔ-Óȉ›ˆÓ Ô˘ ÂÓ¤¯ÔÓÙ·È ¿ÌÂÛ· ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘˘fiÊ˘Û˘ Î·È ÙȘ ÂÍ·ÚÙÒÌÂÓ˜ ·fi ·˘Ù‹ ÏÂÈÙÔ˘Ú-Á›Â˜. ŒÙÛÈ, ÛËÌÂȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ÁÔÓ›‰È· Ù˘·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (growth hormone, GH) Î·È ÙÔ˘˘Ô‰Ô¯¤· ÙÔ˘ ·Ú¿ÁÔÓÙ· ¤ÎÏ˘Û˘ Ù˘ ·˘ÍËÙÈ΋˜ÔÚÌfiÓ˘ (GH-releasing hormone receptor gene,GHRH) ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Û·Ó ·›ÙÈ· Ù˘ ÌÂÌÔӈ̤-Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. ∞˘Ù¤˜ ÔÈ ‰È·-Ù·Ú·¯¤˜ ÛÙË Û‡ÓıÂÛË ‹ ÛÙË ‰Ú¿ÛË Ù˘ GH ÌÔ-ÚÔ‡Ó Ó· ÚÔηϤÛÔ˘Ó Ì›· ÌÂÁ¿ÏË ÔÈÎÈÏ›· ÛÙÔÓÎÏÈÓÈÎfi Ê·ÈÓfiÙ˘Ô ÙˆÓ ·ÛıÂÓÒÓ. À¿Ú¯Ô˘Ó Ù¤ÛÛÂ-ÚȘ ‰È·ÊÔÚÂÙÈÎÔ› Ù‡ÔÈ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘: Ô Ù‡Ô˜ π∞, πµ, ππ Î·È πππ. ∂È-ÚfiÛıÂÙ·, ¤Ó·˜ Û˘Ó¯Ҙ ·˘Í·ÓfiÌÂÓÔ˜ ·ÚÈıÌfi˜·ÛıÂÓÒÓ Ì ÔÏÏ·Ï‹ ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ·¤¯ÂÈ ·Ó·ÊÂÚı› fiÙÈ ¤¯ÂÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ˘˜ ·Ú¿-ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ Ù˘ ˘fiÊ˘Û˘: Pit-1, Prop-1,LHX3 Î·È Hesx-1. ∞˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÌÔÚÔ‡Ó Ó··Ú·ÙËÚËıÔ‡Ó Ì ‰È·ÊÔÚÂÙÈ΋ Û˘¯ÓfiÙËÙ· ÛÙÔ˘˜·ÛıÂÓ›˜. ∏ ¯Ú‹ÛË Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜ Î·È Ù˘ÁÂÓÂÙÈ΋˜ ÛÙË ‰È¿ÁÓˆÛË ·˘ÙÒÓ ÙˆÓ ·ı‹ÛˆÓÌÔÚ› Ó· ÂÍ·ÛÊ·Ï›ÛÂÈ Ì›· ÈÔ ÛˆÛÙ‹ ÚÔÛ¤ÁÁÈÛËÛÙÔ˘˜ ıÂڷ¢ÙÈÎÔ‡˜ ¯ÂÈÚÈÛÌÔ‡˜.

§¤ÍÂȘ ÎÏÂȉȿ: ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘,ÁÔÓ›‰ÈÔ GH, Pit-1, Prop-1, LHX3.

�Abstract: Some non-organic causes for growthhormone deficiency (GHD) can be attributed togenetic defects within the hypothalamo-pituitaryaxis. Recent advances have led to thecharacterization of a number of genes which aredirectly involved in pituitary development andrelated functions. Micromutations within the growthhormone (GH) and GH-releasing hormone receptorgene (GHRH) have been detected as a cause ofisolated GHD. The resulting abnormalities in thesynthesis or the activity of GH can give rise to awide variation in the clinical phenotype of thepatient. Four different types of isolated GHdeficiency (IGHD) have been described: type IA,type IB and types II and III. In addition, increasingnumbers of patients with combined pituitaryhormone deficiencies (CGHD) have been reported,presenting mutations within pituitary transcriptionfactors Pit-1, Prop-1, LHX3 and Hesx-1. Thesevarious defects can be observed with differentfrequencies in clinical practice. The use ofmolecular and genetic diagnostic methods forcertain cases of GH deficiency can provide thebasis for a more accurate approach to therapeuticmanagement.

Key words: growth hormone deficiency (GHD),gene GH, Pit-1, Prop-1, LHX3.

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·89

Ë È‰ÈÔ·ı‹˜ ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ GH(Idiopathic GHD) ÂÚÈÏ·Ì‚¿ÓÂÈ fiϘ ÙȘ ÎÏÈÓÈΤ˜ÂÚÈÙÒÛÂȘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ÁÈ·ÙȘ Ôԛ˜ ‰ÂÓ ˘¿Ú¯ÂÈ ÂÌÊ·Ó‹˜ ·ÈÙ›· (6). ¶·Ú’ fiÏ··˘Ù¿, ÔÈ ·Ú·ÙËÚ‹ÛÂȘ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ 5-30% ·˘-ÙÒÓ ÙˆÓ ÂÚÈÙÒÛÂˆÓ ¤¯ÂÈ Û˘ÁÁÂÓ›˜ ÚÒÙÔ˘ ‚·ı-ÌÔ‡ Ì ·Ó·Ú΋ ۈ̷ÙÈ΋ ·Ó¿Ù˘ÍË, ÁÂÁÔÓfi˜Ô˘ ÂÈÛËÌ·›ÓÂÈ fiÙÈ ÌÔÚ› Ó· ˘Ê›ÛÙ·Ù·È Ì›· Èı·-Ó‹ ÁÂÓÂÙÈ΋ ‰È·Ù·Ú·¯‹ (7).

∏ ·Ó¿ÚÎÂÈ· Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ÌÔÚ›ӷ Â›Ó·È ÌÂÌÔӈ̤ÓË (Isolated growth hormonedeficiency, IGHD) ‹ Ó· Û˘Ó‰˘¿˙ÂÙ·È Ì ·Ó¿ÚÎÂÈ·Î·È ¿ÏÏˆÓ ˘ÔÊ˘ÛÈ·ÎÒÓ ÔÚÌÔÓÒÓ (Multiplepituitary hormone deficiency, MPHD).

¶ÚfiÛÊ·Ù˜ ÂÈÛÙËÌÔÓÈΤ˜ ÚfiÔ‰ÔÈ, fiˆ˜ Ë·Ó¿Ï˘ÛË D¡∞, ¤¯Ô˘Ó Ô‰ËÁ‹ÛÂÈ ÛÙËÓ Ù·˘ÙÔÔ›ËÛËÂÓfi˜ ·ÚÈıÌÔ‡ ÁÔÓȉ›ˆÓ, Ù· ÔÔ›· Â›Ó·È ·Â˘ı›·˜ÂÌÏÂÎfiÌÂÓ· ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ Î·È ÙȘÂÍ·ÚÙÒÌÂÓ˜ ·fi ·˘Ù‹ ÏÂÈÙÔ˘ÚÁ›Â˜. ªÂÚÈο ÂÍ ·˘-ÙÒÓ ¤¯Ô˘Ó ·ÔÌÔÓˆı› ·Â˘ı›·˜ ÛÙÔÓ ¿ÓıÚˆÔ,ÂÓÒ ¿ÏÏ· ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛÙ› ·fi ÂÓÔ¯ÔÔ›ËÛË ÛÂ˙ˆÈο ÌÔÓ٤Ϸ ·Ó·ÚÎÔ‡˜ ·Ó¿Ù˘Í˘ (8).

∞Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘∏ ˘fiÊ˘ÛË ·ÔÙÂÏÂ›Ù·È ·fi ÙÔÓ ÚfiÛıÈÔ ÏÔ‚fi,

Ô ÔÔ›Ô˜ ·ÔÙÂÏ› Î·È ÙÔ 75% ÙÔ˘ ‚¿ÚÔ˘˜ ÙÔ˘ ·‰¤-Ó· Î·È ÚÔ¤Ú¯ÂÙ·È ·fi ÚÔÛÂ΂ÔÏ‹ ÙÔ˘ ¤Íˆ ‚Ï·-ÛÙÈÎÔ‡ ‰¤ÚÌ·ÙÔ˜ (ı‡Ï·Î·˜ ÙÔ˘ Rantke) Î·È ·fiÙÔÓ Ô›ÛıÈÔ ÏÔ‚fi, Ô ÔÔ›Ô˜ ÚÔ¤Ú¯ÂÙ·È ·fi Ó¢ÚÈ-ο ·ÙÙ·Ú· ÙÔ˘ ‰¿ÊÔ˘˜ Ù˘ 3˘ ÎÔÈÏ›·˜. OÈ ÔÚ-ÌfiÓ˜ ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Û˘ÓÙ›ıÂÓÙ·È ·fi ¤ÓÙ‰ȷÊÔÚÂÙÈΤ˜ ÔÌ¿‰Â˜ ÂÎÎÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (ۈ̷-ÙÔÙÚfi·, ÁÔÓ·‰ÔÙÚfi·, Ï·ÎÙÔÙÚfi·, ı˘ÚÂÔÙÚfi·Î·È ÎÔÚÙÈÎÔÙÚfi·), ˘fi ÙËÓ Â›‰Ú·ÛË ˘Ôı·Ï·ÌÈ-ÎÒÓ ÔÚÌÔÓÒÓ. ∏ ÂͤÏÈÍË ÙˆÓ Î˘ÙÙ¿ÚˆÓ ·˘ÙÒÓ Î·Ù¿ÙËÓ ·Ú¯¤ÁÔÓË ÂÌÊ¿ÓÈÛ‹ ÙÔ˘˜ Û˘Ì‚·›ÓÂÈ Û ·˘ÛÙË-Ú‹ ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹. ŒÙÛÈ, ÚÒÙ· ÌÔÚÔ‡Ó Ó· ·Ó·-ÁÓˆÚÈÛÙÔ‡Ó Ù· ÎÔÚÙÈÎÔÙÚfi· ·ÙÙ·Ú·, ÛÙË Û˘Ó¤-¯ÂÈ· Ù· ÁÔÓ·‰ÔÙÚfi· Î·È Ù· ı˘ÚÂÔÙÚfi· ηÈ, Ù¤-ÏÔ˜, ÂÌÊ·Ó›˙ÔÓÙ·È Ù· ۈ̷ÙÔÏ·ÎÙÔÙÚfi·(somatolactotropes cells) Ô˘ Â›Ó·È Úfi‰ÚÔÌ· ·Ù-Ù·Ú· ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ Î·È ÙˆÓ Ï·ÎÙÔÙÚfiˆÓ΢ÙÙ¿ÚˆÓ. ∏ ‰È·ÊÔÚÔÔ›ËÛË Î·È Ô ÔÏÏ·Ï·ÛÈ·-ÛÌfi˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ·˘ÙÒÓ, Ô˘ Ï·Ì‚¿ÓÂÈ ¯ÒÚ·ÛÙ· ÚÒÙ· ÛÙ¿‰È· Ù˘ ÂÌ‚Ú˘˚΋˜ ·Ó¿Ù˘Í˘ (12Ë-15Ë ÂÌ‚Ú˘˚΋ Ë̤ڷ), ÙÂÏÂ›Ù·È ˘fi ÙËÓ Â›‰Ú·ÛËÔÚÈÛÌ¤ÓˆÓ ÚˆÙÂ˚ÓÒÓ (DNA-binding proteins), ÔÈÔԛ˜ ÔÓÔÌ¿˙ÔÓÙ·È ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜(Homeodomain containing transcription factors)(5,8-10).

¶·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors) ∆· ÁÔÓ›‰È·, ÂÎÙfi˜ ·fi ÙËÓ ÏËÚÔÊÔÚ›· ÁÈ· ÙË ‰Ô-

Ì‹ Ù˘ ÚˆÙ½Ó˘, ÙËÓ ÔÔ›· Έ‰ÈÎÔÔÈÔ‡Ó (‰ÔÌÈ΋

ÂÚÈÔ¯‹ ÙÔ˘ ÁÔÓȉ›Ô˘), ÂÚȤ¯Ô˘Ó Î·È ÙËÓ ÏËÚÔÊÔ-Ú›· ÁÈ· ÙË Ú‡ıÌÈÛË Ù˘ ›‰È·˜ ÙÔ˘˜ Ù˘ ¤ÎÊÚ·Û˘(Ú˘ıÌÈÛÙÈ΋ ÂÚÈÔ¯‹). OÈ ·ÏÏËÏÔ˘¯›Â˜ Ô˘ ÂÓ¤¯ÔÓÙ·ÈÛÙË Ú‡ıÌÈÛË Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ ‰È·ÎÚ›ÓÔÓÙ·ÈÛ ‰‡Ô ηÙËÁÔڛ˜: Ë Ì›· ÂÚÈÔ¯‹ Ô˘ ‚Ú›ÛÎÂÙ·È ÎÔ-ÓÙ¿ ÛÙÔ ÛËÌÂ›Ô ¤Ó·Ú͢ Ù˘ ÌÂÙ·ÁÚ·Ê‹˜ ϤÁÂÙ·È˘ÔÎÈÓËÙ‹˜ (Promoter) Î·È Ë ¿ÏÏË Ï¤ÁÂÙ·È ÂÓÈÛ¯˘Ù‹˜(Enhancer). ™ÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ˘ÔÎÈÓËÙ‹ ˘¿Ú¯Ô˘ÓηıÔÚÈṲ̂Ó˜ ı¤ÛÂȘ, ÛÙȘ Ôԛ˜ ÚÔÛ‰¤ÓÔÓÙ·È Û˘-ÁÎÂÎÚÈ̤Ó˜ Ú˘ıÌÈÛÙÈΤ˜ ÚˆÙ½Ó˜, ÔÈ ·Ú¿ÁÔÓÙ˜ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors), ÁÈ· ÙË Ú‡ıÌÈÛËÙ˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘.

™ÙË ‰È·‰Èηۛ· ÌÂÙ·ÁÚ·Ê‹˜ ÙÔ˘ DNA Û RNAÛ˘ÌÌÂÙ¤¯Ô˘Ó ÔÈ RNA-ÔÏ˘ÌÂÚ¿Û˜ (π, ππ Î·È πππ). ∞fi·˘Ù¤˜, Ë RNA ÔÏ˘ÌÂÚ¿ÛË II, ·Ó·ÁÓˆÚ›˙ÂÈ ÛÙËÓ Â-ÚÈÔ¯‹ ÙÔ˘ ˘ÔÎÈÓËÙ‹ Û˘ÁÎÂÎÚÈ̤Ó˜ ·ÏÏËÏÔ˘¯›Â˜(˙‡ÁË ‚¿ÛˆÓ), ÛÙȘ Ôԛ˜ Î·È ÚÔÛ‰¤ÓÂÙ·È. °È·ÙËÓ ¤Ó·ÚÍË, fï˜, Ù˘ ÌÂÙ·ÁÚ·Ê‹˜ ¯ÚÂÈ¿˙ÂÙ·È Ó·Û˘Ó‰ÂıÔ‡Ó ÛÙÔ DNA Î·È ¿ÏϘ ÚˆÙ½Ó˜, ÔÈ ÔÔ›-˜ Â›Ó·È ÔÈ ÁÓˆÛÙÔ› ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜(Transcription factors). OÈ ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·-Ê‹˜, ‰ËÏ·‰‹, Â›Ó·È Ô “ÌÔÚÈ·Îfi˜ ‰È·ÎfiÙ˘” - Ë··Ú¯‹ - Ô˘ ÌÔÚ› Ó· ‰ÈÂÁ›ÚÂÈ ‹ Ó· ηٷÛÙ›ÏÂÈÙËÓ ¤ÎÊÚ·ÛË ÂÓfi˜ ÁÔÓȉ›Ô˘ (11,12).

°ÔÓ›‰È· Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙÔ Û¯ËÌ·ÙÈÛÌfi Î·È ÙËÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡-˘fiÊ˘Û˘

·) °ÔÓ›‰ÈÔ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GHI): Έ‰È-ÎÔÔÈ› ÙËÓ ÂÓÙÔÏ‹ ÁÈ· ÙË Û‡ÓıÂÛË Ù˘ ˘ÔÊ˘ÛÈ·-΋˜ GH.

‚) °ÔÓ›‰ÈÔ ÙÔ˘ GHRHR: Έ‰ÈÎÔÔÈ› ÙÔÓ ˘Ô‰Ô-¯¤·, Ì ÙÔÓ ÔÔ›Ô Û˘Ó‰¤ÂÙ·È Ô ·Ú¿ÁÔÓÙ·˜ ¤ÎÏ˘-Û˘ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growth hormonereleasing hormone-GHRH) Î·È ‰ÈÂÁ›ÚÂÈ ÙËÓ ¤ÎÎÚÈ-ÛË GH.

Á) °ÔÓ›‰È· POUIF-1, Prop-1, LHX3, Hesx-1: ›ӷȓÔÌÔÈÔÙÈο” ÁÔÓ›‰È· (homeobox genes), Ù· ÔÔ›·Îˆ‰ÈÎÔÔÈÔ‡Ó Ì›· ÔÈÎÔÁ¤ÓÂÈ· ·Ú·ÁfiÓÙˆÓ ÌÂÙ·-ÁÚ·Ê‹˜ (transcription factors), ÔÈ ÔÔ›ÔÈ ÂÓ¤¯ÔÓÙ·ÈÛÙËÓ ÔÚÁ·ÓÔÁ¤ÓÂÛË ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fi-Ê˘Û˘ Î·È ÛÙË Ú‡ıÌÈÛË Ù˘ ¤ÎÎÚÈÛ˘ GH.

ªÂÙ·ÏÏ¿ÍÂȘ Û fiÏ· ·˘Ù¿ Ù· ÁÔÓ›‰È· ¤¯Ô˘Ó˘¿ÚÍÂÈ Î·È ÂÎÊÚ¿˙ÔÓÙ·È Ì ·Ó¿ÚÎÂÈ· Ù˘ GH ‹Î·È ¿ÏÏˆÓ ÔÚÌÔÓÒÓ (6,8,13).

¢È·Ù·Ú·¯¤˜ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH∆o ÁÔÓ›‰ÈÔ GH1, Ô˘ Â›Ó·È ˘Â‡ı˘ÓÔ ÁÈ· ÙË Û‡Ó-

ıÂÛË Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, Â›Ó·È ¤Ó· ·fi Ù·ÚÒÙ· ·ÓıÚÒÈÓ· ÁÔÓ›‰È· Ô˘ Ù·˘ÙÔÔÈ‹ıËÎ·Ó Î·È‰ڿ˙ÂÙ·È ÛÙÔ ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ 17q23(8,14). OÈ ÚÒÙ˜ ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÁÔÓȉ›-Ô˘ GH1 ·Ó·Î·Ï‡ÊıËÎ·Ó ÚÈÓ ·fi 20 ÂÚ›Ô˘ ¯Úfi-ÓÈ· ·fi ÙÔÓ John Phillips Î·È ¯·Ú·ÎÙËÚ›ÛÙËÎ·Ó ˆ˜·ÒÏÂȘ ÙÌ‹Ì·ÙÔ˜ (deletion) ÙÔ˘ ÁfiÓÔ˘ Ù˘ GH

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(15). ÀÔÏÔÁ›˙ÂÙ·È fiÙÈ ÂÚ›Ô˘ ÙÔ 13-15% ÙˆÓ·ÛıÂÓÒÓ Ì ÛÔ‚·Ú‹ ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘-ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (>-4,5 SD ÛÙÔ ‡„Ô˜) ¤¯ÂÈ ·˘ÙÔ‡ÙÔ˘ ›‰Ô˘˜ ÙË ÌÂÙ¿ÏÏ·ÍË ÛÙÔ ÁÔÓ›‰ÈÔ GH1 (16,17).

∞ÚÁfiÙÂÚ·, ·Ú·ÙËÚ‹ıËÎ·Ó Î·È ¿ÏϘ ‰È·Ù·Ú·-¯¤˜ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË Û‡Ó-ıÂÛË Î·È ÙË ‰Ú·ÛÙËÚÈfiÙËÙ· Ù˘ GH Î·È ÔÈ Ôԛ˜ÌÔÚ› Ó· Â›Ó·È ˘Â‡ı˘Ó˜ ÁÈ· ÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÎÏÈ-ÓÈÎÔ‡˜ Ê·ÈÓfiÙ˘Ô˘˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ·Ó¿ÚÎÂÈ··˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. Œ¯Ô˘Ó ÂÚÈÁÚ¿ÊÂÈ Ù¤ÛÛÂÚȘÔÈÎÔÁÂÓ›˜ Ù‡ÔÈ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍË-ÙÈ΋˜ ÔÚÌfiÓ˘. OÈ ‰‡Ô ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈ-fiÌÂÓÔ ÛˆÌ·ÙÈÎfi ¯·Ú·ÎÙ‹Ú· (IGHD πA Î·È πµ),¤Ó·˜ Ì ÂÈÎÚ·ÙÔ‡ÓÙ· (IGHD II) Î·È Ô Ù¤Ù·ÚÙÔ˜ ÌÂÊ˘ÏÔÛ‡Ó‰ÂÙÔ (IGHD IIπ) (16).

™ÙÔÓ ÚÒÙÔ Ù‡Ô π∞ Ù˘ ÌÂÌÔӈ̤Ó˘ ·Ó¿Ú-ÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÔÈ ‰È·Ù·Ú·¯¤˜ (defects)ÛÙÔ ÁÔÓ›‰ÈÔ GH1 ·ÊÔÚÔ‡Ó Â›Ù Û ·ÒÏÂÈ· ÌÂÁ¿-ÏÔ˘ ·ÚÈıÌÔ‡ ‚¿ÛÂˆÓ (deletion) ‹ Û ÌÂÙ·ÏÏ¿ÍÂÈ˜Ô˘ ÚÔηÏÔ‡Ó ‰È·Ù·Ú·¯‹ ÙÔ˘ Ï·ÈÛ›Ô˘ ·Ó¿ÁÓˆ-Û˘ (frame-shift mutation) ‹ Û ÌÂÙ·ÏÏ¿ÍÂȘ fiÔ˘˘¿Ú¯ÂÈ ÌÂÙ·ÙÚÔ‹ ÂÓfi˜ ·ÌÈÓÔͤԘ Û Έ‰ÈÎfiÓÈÔÏ‹Í˘, ·ÓÂÚÌËÓ‡ÛÈÌË ÌÂÙ¿ÏÏ·ÍË (nonsensemutation) (16,18-20). OÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹ÎÔ˘Ó Û·˘ÙfiÓ ÙÔÓ Ù‡Ô ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘·Ó·ÏÔÁÔ‡Ó ÂÚ›Ô˘ ÛÙÔ 10% ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÂ-ÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (21) ηȤ¯Ô˘Ó Û˘Ó‹ıˆ˜ Ôχ ÎÔÓÙfi ·Ó¿ÛÙËÌ·, Ï‹ÚË ¤Ï-ÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Î·È ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔ-Ú¤˜, fiÙ·Ó ÙÔ˘˜ ¯ÔÚËÁÂ›Ù·È GH, ·Ú¿ÁÔ˘Ó ·ÓÙÈÛÒ-Ì·Ù· ¤Ó·ÓÙÈ ·˘Ù‹˜.

™ÙÔÓ Ù‡Ô IGHD πµ, ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓ›‰ÈÔ˘GH ·ÊÔÚÔ‡Ó Û ˘ÔηٷÛÙ¿ÛÂȘ ‚¿ÛÂˆÓ Ô˘ ÂË-Ú¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ Î·È Ù˘ ·-Ó·Û˘ÁÎfiÏÏËÛ˘ (splicing) ÙÔ˘ RNA (16). OÈ ·ÛıÂ-Ó›˜ Ô˘ ·Ó‹ÎÔ˘Ó Û ·˘ÙfiÓ ÙÔÓ Ù‡Ô ¤¯Ô˘Ó ¯·ÌË-Ϥ˜ ÙÈ̤˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ηϋ ·ÓÙ·fiÎÚÈÛËÛ ıÂڷ›· ˘ÔηٿÛÙ·Û˘ Ì GH Î·È ‰ÂÓ ·Ó·-Ù‡ÛÛÔ˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ·˘Ù‹˜ (16,18).

™ÙÔÓ Ù‡Ô IGHD ππ, ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔÙ˘ GH ·ÊÔÚÔ‡Ó - Î·È Û ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË - Û¢ÔηٷÛÙ¿ÛÂȘ ‹ ·ÒÏÂȘ ‚¿ÛÂˆÓ Ô˘ ÂËÚ¿-˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ ÙˆÓ ÈÓÙÚÔÓ›ˆÓÎ·È Ù˘ ¤ÓˆÛ˘ ÙˆÓ Â͈ӛˆÓ (Ì¿ÙÈÛÌ·-splicing) ÙÔ˘RNA (splice site mutation) (16,22-24). OÈ ·ÛıÂÓ›˜Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, Ô˘ ·Ó‹ÎÔ˘ÓÛÙÔÓ Ù‡Ô IGHD II, ¤¯Ô˘Ó Î·È ·˘ÙÔ› ÎÔÓÙfi ·Ó¿ÛÙË-Ì·, ¯·ÌËϤ˜ ÙÈ̤˜ GH, ηϋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂ-ڷ›· ˘ÔηٿÛÙ·Û˘ Î·È ‰ÂÓ ·Ó·Ù‡ÛÛÔ˘Ó ·ÓÙÈ-ÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ GH.

∆¤ÏÔ˜, ÔÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹ÎÔ˘Ó ÛÙÔÓ Ù‡ÔIGHD III ·ÚÔ˘ÛÈ¿˙Ô˘Ó ¤ÏÏÂÈ„Ë Ù˘ ·˘ÍËÙÈ΋˜ ÔÚ-ÌfiÓ˘, ÂÓÒ ÌÂÚÈÎÔ› ·fi ·˘ÙÔ‡˜ ¤¯Ô˘Ó Î·È ·Á·ÌÌ·-ÛÊ·ÈÚÈÓ·ÈÌ›· (25). OÈ ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘

˘Ê›ÛÙ·ÓÙ·È ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH Û ·˘Ù¤˜ ÙȘ ÂÚÈ-ÙÒÛÂȘ, ‰ÂÓ Â›Ó·È Ï‹Úˆ˜ ÁÓˆÛÙ¤˜ (26,27).

ªÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ ÙÔ˘ ˘Ô‰Ô¯¤· GHRH™ÙÔÓ ÚfiÛıÈÔ ÏÔ‚fi Ù˘ ˘fiÊ˘Û˘, ÛÙ· ۈ̷ÙÔ-

ÙÚfi· ·ÙÙ·Ú·, ÙÔ ˘Ôı·Ï·ÌÈÎfi ÂÚ¤ıÈÛÌ· ÁÈ· ÙÔÓ·Ú¿ÁÔÓÙ· ¤ÎÏ˘Û˘ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growthhormone releasing hormone, GHRH) ·Ó·ÁÓˆÚ›˙ÂÙ·ÈÎ·È ÌÂٷʤÚÂÙ·È ·fi ¤Ó·Ó ÂȉÈÎfi GHRH ˘Ô‰Ô¯¤·(receptor). O GHRHR ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ˘Ô‰Ô¯¤ˆÓ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙÔ Û‡ÛÙËÌ· ÙˆÓ G-ÚˆÙÂ˚ÓÒÓ (G-protein coupled receptors). ∆Ô Û‡ÛÙË-Ì· ÙˆÓ G-ÚˆÙÂ˚ÓÒÓ ·ÔÙÂÏ› ¤Ó· ‰È¿ÌÂÛÔ ·Ú¿ÁÔ-ÓÙ· Ô˘ ÌÂٷʤÚÂÈ ÙÔ ·Ú¯ÈÎfi ÂÚ¤ıÈÛÌ· ·fi ÙÔÓ ˘Ô-‰Ô¯¤· ÚÔ˜ ÙÔ ÂÓ˙˘ÌÈÎfi Û‡ÛÙËÌ· Ô˘ ·Ú¿ÁÂÈ ÙÔÓ“‰Â‡ÙÂÚÔ ·ÁÁÂÏÈÔÊfiÚÔ” (28).

∆o ÁÔÓ›‰ÈÔ ÙÔ˘ GHRHR Ù·˘ÙÔÔÈ‹ıËΠÙÔ 1992Î·È Â‰Ú¿˙ÂÙ·È ÛÙÔ 7Ú ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ (29).O GHRH ˘Ô‰Ô¯¤·˜ ¤¯ÂÈ ¤Ó· ÛËÌ·ÓÙÈÎfi ÚfiÏÔÛÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ÛÙË ‰È·ÊÔÚÔÔ›ËÛËÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ ΢ÙÙ¿ÚˆÓ Ù˘ ˘fiÊ˘Û˘ ηÈÚ˘ıÌ›˙ÂÈ ÙËÓ ÈηÓfiÙËÙ¿ ÙÔ˘˜ Ó· ·Ú¿ÁÔ˘Ó ·˘ÍËÙÈ-΋ ÔÚÌfiÓË (30).

∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤¯Ô˘Ó ·Ó·ÊÂÚı› ‰È·Ù·Ú·-¯¤˜ ÙÔ˘ ÁÔÓ›‰ÈÔ˘ GHRHR, ÔÈ Ôԛ˜ ·ÊÔÚÔ‡Ó ÛÙË ÌÂ-Ù·ÙÚÔ‹ ÂÓfi˜ ·ÌÈÓÔͤԘ Û Έ‰ÈÎfiÓÈÔ Ï‹Í˘, ·ÓÂÚ-ÌËÓ‡ÛÈÌË ÌÂÙ¿ÏÏ·ÍË (nonsense mutation) ‹ ÌÂÙ·Ï-Ï¿ÍÂȘ Ô˘ ·ÊÔÚÔ‡Ó Û ˘ÔηٷÛÙ¿ÛÂȘ ‚¿ÛÂˆÓ Î·ÈÂËÚ¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ Î·È ÙË˜Â·Ó·Û˘ÁÎfiÏÏËÛ˘ (splicing) ÙÔ˘ RNA (splice sitemutation) (31-37). ŸÏ˜ ·˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÌÂÙ·‚È-‚¿˙ÔÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú·.

OÈ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ GHRHR ÁÔÓ›-‰ÈÔ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÔ‚·Ú‹ ·Ó¿ÚÎÂÈ· GH (¯ˆÚ›˜¤ÏÏÂÈ„Ë ¿ÏÏˆÓ ˘ÔÊ˘ÛÈ·ÎÒÓ ÔÚÌÔÓÒÓ) Î·È ˘Ô-Ï·Û›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÂÓÒ¤¯Ô˘Ó ηϋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· ˘Ôηٿ-ÛÙ·Û˘ Ì GH.

°ÔÓ›‰ÈÔ POUIF-1 (Pit-1) Î·È ÌÂÙ·ÏÏ¿ÍÂȘ ∆Ô ÁÔÓ›‰ÈÔ Pit-1 (Ë Â›ÛËÌË ÔÓÔÌ·Û›· ÙÔ˘ ÔÔ›Ô˘,

Û‹ÌÂÚ·, Â›Ó·È POUIF-1) Â›Ó·È ¤Ó· ̤ÏÔ˜ Ù˘ ÔÈÎÔÁ¤-ÓÂÈ·˜ (POU) ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ Î·È Â›Ó·È˘Â‡ı˘ÓÔ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ (38).

O POUπF-1 Ù·˘ÙÔÔÈ‹ıËΠÁÈ· ÚÒÙË ÊÔÚ¿ ÙÔ1988 (39) Î·È ‚Ú¤ıËΠfiÙÈ ÂÓÙÔ›˙ÂÙ·È ÛÙÔ 3ƒ11 ·Ó-ıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ (40). ∏ Pit (1) ÚˆÙ½ÓË ·ÓÈ-¯Ó‡ÂÙ·È ÛÙÔÓ ˘Ú‹Ó· ÙÚÈÒÓ Î˘ÙÙ·ÚÈÎÒÓ ÛÂÈÚÒÓÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÙˆÓ ÛˆÌ·ÙÔ-ÙÚfiˆÓ, ÙˆÓ Ï·ÎÙÔÙÚfiˆÓ Î·È ÙˆÓ ı˘ÚÂÔÂȉÔÙÚfi-ˆÓ (41,42). ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ô ·Ú¿ÁˆÓ Pit Â›Ó·È ··Ú·›ÙËÙÔ˜ ·ÊÂÓfi˜ ÁÈ· ÙËÓ ·Ú¯È΋ ÂÌÊ¿ÓÈÛË·˘ÙÒÓ ÙˆÓ Î˘ÙÙ·ÚÈÎÒÓ ÛÂÈÚÒÓ, ·ÊÂÙ¤ÚÔ˘ ÁÈ· ÙËÌÂÙ¤ÂÈÙ· ‰È¤ÁÂÚÛ‹ ÙÔ˘˜.

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ªÂÙ·ÏÏ¿ÍÂȘ, ÂÔ̤ӈ˜, ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔÚÔηÏÔ‡Ó Û˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘ÁÈ· ·˘ÍËÙÈ΋ ÔÚÌfiÓË (GH), ÚÔÏ·ÎÙ›ÓË (PRL) ηÈı˘ÚÂÔÙÚfiÔ ÔÚÌfiÓË (TSH). ∏ ÚÒÙË ·ÓıÚÒÈÓËÌÂÙ¿ÏÏ·ÍË ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ ·Ó·Ê¤ÚıËΠÙÔ1992, Û ·È‰› ÌÂ Û˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· Ù˘·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Î·È Ù˘ ÚÔÏ·ÎÙ›Ó˘ (PRL)(43). ∏ ‰È·Ù·Ú·¯‹ ÔÚÌÔÓÒÓ Ô˘ ÔÊ›ÏÂÙ·È Û ÌÂ-Ù¿ÏÏ·ÍË ÙÔ˘ POUIF-1 ÁÔÓȉ›Ô˘, ÌÂÙ·‚È‚¿˙ÂÙ·È Î˘-Ú›ˆ˜ Ì ÙÔÓ ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú· (43-49).À¿Ú¯ÂÈ fï˜ Î·È ‰È·Ù·Ú·¯‹ Ô˘ ÌÂÙ·‰›‰ÂÙ·È ÌÂÙÔÓ ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú·, ·Ó¿ÏÔÁ· Ì ÙË ı¤ÛËÙ˘ ÌÂÙ¿ÏÏ·Í˘ ÛÙÔ ÁÔÓ›‰ÈÔ (38,50-53).

∆· ›‰Ë ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Ô˘ ¤¯Ô˘Ó ·Ó·ÊÂÚı›̤¯ÚÈ Û‹ÌÂÚ· ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ, Â›Ó·È ‰Ò‰Âη(54). ∆· ÂÓÓ¤· ·ÊÔÚÔ‡Ó Û ·ÚÂÚÌËÓ‡ÛÈ̘ ÌÂ-Ù·ÏÏ¿ÍÂȘ (missence mutation) (45,47,48, 50-53),Ù· ‰‡Ô Û ·ÓÂÚÌËÓ‡ÛÈ̘ (nonsense mutation)(43,46,47) Î·È ÙÔ ¤Ó· Û ¤ÏÏÂÈÌÌ· ‚¿ÛˆÓ(deletion) (44).

O Ê·ÈÓfiÙ˘Ô˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔÁÔÓ›‰ÈÔ POUIF-1 ÔÈΛÏÏÂÈ Î·È ‰ÂÓ ¤¯ÂÈ Û¯¤ÛË Ì ÙÔ›‰Ô˜ ÙˆÓ ÌÂÙ·ÏϿ͈Ó, Ô‡Ù Ì ÙÔÓ ÙÚfiÔ Ô˘·˘Ù¤˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤¯Ô˘Ó ¤Ï-ÏÂÈ„Ë GH, PRL Î·È TSH (9). ªÂÚÈÎÔ› ·fi ·˘ÙÔ‡˜¤¯Ô˘Ó ˘Ôı˘ÚÂÔÂȉÈÛÌfi, ·ÚÎÂÙfi ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·ÚÈÓ ÂÌÊ·ÓÈÛÙ› Ë ¤ÏÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÂÓÒÛ ¿ÏÏÔ˘˜ ·ÛıÂÓ›˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÌÂÙ¿ ÙËÓ ¤Ó·Ú-ÍË Ù˘ ıÂڷ›·˜ Ì GH (55).

OÈ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ POUIF-1 ÁÔÓ›-‰ÈÔ ‰Â›¯ÓÔ˘Ó Ó· ÛÙÂÚÔ‡ÓÙ·È ÙËÓ ÂͤÏÈÍË ÙˆÓ ÛˆÌ·-ÙÔÙÚfiˆÓ, ÙˆÓ Ï·ÎÙÔÙÚfiˆÓ Î·È ÙˆÓ ı˘ÚÂÔÂȉÔ-ÙÚfiˆÓ ΢ÙÙ¿ÚˆÓ Ù˘ ˘fiÊ˘Û˘ Î·È ÁÈ’ ·˘Ùfi ¯ÚÂÈ-¿˙ÔÓÙ·È ıÂڷ›· ˘ÔηٿÛÙ·Û˘.

°ÔÓ›‰ÈÔ Prop-1 Î·È ÌÂÙ·ÏÏ¿ÍÂȘ ∆o Prop-1 ÁÔÓ›‰ÈÔ Îˆ‰ÈÎÔÔÈ› ¤Ó·Ó ·Ú¿ÁÔÓÙ·

ÌÂÙ·ÁÚ·Ê‹˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ “ÔÌÔÈÔÂÚÈÔ¯‹”(homeodomain containing transcription factor) ηÈıˆÚÂ›Ù·È Ô˘ÛÈ·ÛÙÈÎfi ÁÈ· ÙËÓ ¤ÎÊÚ·ÛË Ù˘ PitÚˆÙ½Ó˘ ÛÙ· ۈ̷ÙÔÙÚfi·, Ï·ÎÙÔÙÚfi· Î·È ı˘-ÚÂÔÂȉÔÙÚfi· ·ÙÙ·Ú· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘˘fiÊ˘Û˘. ∏ ¤ÎÊÚ·Û‹ ÙÔ˘ Á›ÓÂÙ·È Î·Ù¿ ÙË ‰È¿Ú-ÎÂÈ· Ù˘ ÂÌ‚Ú˘˚΋˜ ·Ó¿Ù˘Í˘ Ù˘ ˘fiÊ˘Û˘ ηÈÚÔËÁÂ›Ù·È ¿ÓÙÔÙ Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ Pit ÁÔÓ›‰È-Ô˘. °È’ ·˘Ùfi ÙÔ ÏfiÁÔ, ÔÓÔÌ¿˙ÂÙ·È Î·È ÚÔÊ‹Ù˘ ÙÔ˘Pit (Prophet of Pit) (8,56,57).

∆Ô ÁÔÓ›‰ÈÔ Prop-1 ÛÙÔÓ ¿ÓıÚˆÔ Â‰Ú¿˙ÂÙ·È ÛÙÔ¯ÚˆÌfiۈ̷ 5 (5q35) (58). ∏ ÚÒÙË ·ÓıÚÒÈÓË ÌÂ-Ù¿ÏÏ·ÍË ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ ·Ó·Ê¤ÚıËΠÙÔ 1998Î·È ·fi ÙfiÙ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÂÙ¿ ·ÎfiÌ· ÌÂÙ·Ï-Ï¿ÍÂȘ (8). ŸÏ˜ ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÎÏËÚÔÓÔÌÔ‡ÓÙ·ÈÌ ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú· Î·È ÔÈ ÂÚÈÛÛfiÙÂÚ˜·ÊÔÚÔ‡Ó Û ÌÈÎÚ¿ ÂÏÏ›ÌÌ·Ù· ‚¿ÛÂˆÓ Ô˘ ÚÔη-

ÏÔ‡Ó ‰È·Ù·Ú·¯‹ ÙÔ˘ Ï·ÈÛ›Ô˘ ·Ó¿ÁÓˆÛ˘(frameshift mutation) (59,60) ‹ ·ÏÏ·Á‹ Έ‰ÈÎÔÓ›Ô˘ÛÙÔ mRNA ηÈ, ÂÔ̤ӈ˜, Ï¿ıÔ˜ ·ÌÈÓÔ͇ ÛÙËÓ Ô-Ï˘ÂÙȉÈ΋ ·Ï˘Û›‰· ηٿ ÙË ÌÂÙ¿ÊÚ·ÛË-·ÚÂÚ-ÌËÓ‡ÛÈ̘ ÌÂÙ·ÏÏ¿ÍÂȘ (missence mutation)(58,59,61) ‹ ÚÔηÏÔ‡Ó ·ÓÂÚÌËÓ‡ÛÈ̘ ÌÂÙ·ÏÏ¿-ÍÂȘ (nonsense mutation) (8). O Ê·ÈÓfiÙ˘Ô˜ ÙˆÓ·ÛıÂÓÒÓ ·˘ÙÒÓ ÔÈΛÏÏÂÈ, ÂÓÒ Ë ËÏÈΛ· Ù˘ ‰È¿ÁÓˆ-Û˘ ÂÍ·ÚÙ¿Ù·È ·fi ÙË ‚·Ú‡ÙËÙ· ÙˆÓ Û˘Ìو̿-ÙˆÓ Î·È Î˘Ì·›ÓÂÙ·È ·fi 9 ÌËÓÒÓ Ì¤¯ÚÈ 8 ÂÙÒÓ (61).ªÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ Û˘Óԉ‡ÔÓÙ·È ·fiÛÔ‚·Ú¤˜ Î·È Û˘Ó‰˘·Ṳ̂Ó˜ ·Ó¿ÚÎÂȘ Ù˘ GH,LH, FSH, TSH, Ù˘ ÚÔÏ·ÎÙ›Ó˘ Î·È ›Ûˆ˜ ·ÚÁfiÙÂÚ·Ù˘ ÊÏÔÈÔÙÚfiÔ˘ ÔÚÌfiÓ˘ (ACTH) (62). ŒÙÛÈ,Prop-1 ‰È·Ù·Ú·¯¤˜ Û˘Ó·ÓÙÒÓÙ·È Û¯ÂÙÈο Û˘¯Ó¿ÛÙȘ ÌÂÈÎÙ¤˜ ·Ó¿ÚÎÂȘ Ù˘ ˘fiÊ˘Û˘ (59).

™Â Û‡ÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó ÌÂ-Ù·ÏÏ¿ÍÂȘ ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ, ÔÈ ÔÔ›ÔÈ ¤¯Ô˘Ó Û˘-Ó‹ıˆ˜ Ï‹ÚË ¤ÏÏÂÈ„Ë GH Î·È PRL, ÔÈ ·ÛıÂÓ›˜ ÌÂÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ¤¯Ô˘Ó ¯·ÌËÏ¿ ›‰· ·˘-ÙÒÓ ÙˆÓ ÔÚÌÔÓÒÓ, ÂÓÒ ¤¯Ô˘Ó Ï‹ÚË ¤ÏÏÂÈ„Ë ÁÔÓ·-‰ÔÙÚÔÈÓÒÓ (FSH, LH). ∆Ô ¤Ó· ÙÚ›ÙÔ ÙˆÓ ·ÛıÂÓÒÓ·ÚÔ˘ÛÈ¿˙ÂÈ Î·È ¤ÏÏÂÈ„Ë Ù˘ ÊÏÔÈÔÙÚfiÔ˘ ÔÚÌfi-Ó˘ (ACTH) (8).

™ÙÔ˘˜ ·ÛıÂÓ›˜, ÂÔ̤ӈ˜, Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔProp-1 ÁÔÓ›‰ÈÔ ‰ÂÓ Â›Ó·È ÂÊÈÎÙ‹ Ë ¤ÎÊÚ·ÛË ÙÔ˘ Pit-1 ·fi ÙÔ POUIF-1 ÁÔÓ›‰ÈÔ Î·È, ˆ˜ ÂÎ ÙÔ‡ÙÔ˘, ‰ÂÓ Â›-Ó·È ‰˘Ó·Ùfi Ó· ÂÎÎÚ›ÓÔ˘Ó ·˘ÍËÙÈ΋ ÔÚÌfiÓË (GH),ˆ¯ÚÈÓÔÔÈËÙÈ΋ (LH), ı˘Ï·ÎÈÔÙÚfiÔ (FSH), ÚÔÏ·-ÎÙ›ÓË (PRL), ı˘ÚÂÔÙÚfiÔ (TSH) Î·È ÊÏÔÈÔÙÚfiÔÔÚÌfiÓË (ACTH), Ì ·ÔÙ¤ÏÂÛÌ· Ó· ··ÈÙÂ›Ù·È ıÂ-ڷ›· ˘ÔηٿÛÙ·Û˘ (9).

°ÔÓ›‰ÈÔ L∏Ã3 Î·È ÌÂÙ·ÏÏ¿ÍÂȘ O LHX3 (LIM homeobox3) Â›Ó·È Î·È ·˘Ùfi˜ ¤Ó·˜

·Ú¿ÁÔÓÙ·˜ ÌÂÙ·ÁÚ·Ê‹˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ “ÔÌÔÈ-ÔÂÚÈÔ¯‹” (homeodomain-containing tran-scriptionfactor) Î·È ÂÌÊ·Ó›˙ÂÙ·È Ôχ ÓˆÚ›˜, ηٿ ÙËÓ ÂÔ¯‹Ù˘ ÔÚÁ·ÓÔÁ¤ÓÂÛ˘ Ù˘ ˘fiÊ˘Û˘ ·fi ÙÔ ı‡Ï·ÎÔÙÔ˘ Rathke. O ·Ú¿ÁˆÓ L∏Ã3 ‰Ú· Û˘ÓÂÚÁ·ÙÈο ÌÂÙÔ Pit-1 ÛÙË ÌÂÙ·ÁÚ·Ê‹ ÙˆÓ ÂÓÂÚÁÒÓ ÁÔÓȉ›ˆÓ Ô˘Ú˘ıÌ›˙Ô˘Ó ÙË ‰È·ÊÔÚÔÔ›ËÛË Ù˘ ˘fiÊ˘Û˘ (63).O LHX3 Ú˘ıÌ›˙ÂÈ ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ÙË ‰È·-ÊÔÚÔÔ›ËÛË ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ, Ï·ÎÙÔÙÚfiˆÓ,ı˘ÚÂÔÙÚfiˆÓ Î·È ÁÔÓ·‰ÔÙÚfiˆÓ ΢ÙÙ¿ÚˆÓ Ù˘˘fiÊ˘Û˘ (64).

ªÂÙ·ÏÏ¿ÍÂȘ ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Ôχ ÚfiÛÊ·Ù·ÛÙÔ L∏Ã3 ÁÔÓ›‰ÈÔ Î·È ÚfiÎÂÈÙ·È ÁÈ· ·ÚÂÚÌËÓ‡ÛÈ-̘ ÌÂÙ·ÏÏ¿ÍÂȘ (missence) ‹ ·ÒÏÂȘ ‚¿ÛˆÓ(deletion), ÔÈ Ôԛ˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfi-ÌÂÓÔ ¯·Ú·ÎÙ‹Ú·. OÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÚÔ˘ÛÈ¿˙Ô˘ÓÛÔ‚·Ú‹ ηı˘ÛÙ¤ÚËÛË ÛÙËÓ ·Ó¿Ù˘ÍË Î·È ¤¯Ô˘Ó ÎÔ-ÓÙfi Î·È ¯ÔÓ‰Úfi ·˘¯¤Ó· Ì ÂÚÈÔÚÈṲ̂ÓË ÛÙÚÔÊ‹Ù˘ ÎÂÊ·Ï‹˜. ∂›Û˘, ÂÌÊ·Ó›˙Ô˘Ó ˘ÔÏ·Û›· Ù˘

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˘fiÊ˘Û˘ Î·È ‰‡Ó·Ù·È Ó· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‰È·Ù·Ú·-¯¤˜ ÙÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (65,66).

∞ÛıÂÓ›˜ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ LHX3 ÁÔÓ›‰ÈÔ ·-ÚÔ˘ÛÈ¿˙Ô˘Ó ‰È·Ù·Ú·¯¤˜ Û fiϘ ÙȘ ÔÚÌÔÓÈΤ˜ÛÂÈÚ¤˜ ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÏËÓÙ˘ ÊÏÔÈÔÙÚfiÔ˘ ÔÚÌfiÓ˘ (ACTH), ÁÈ’ ·˘Ùfi ¯ÚÂÈ-¿˙ÔÓÙ·È Ì·ÎÚÔ¯ÚfiÓÈ· ıÂڷ›· ˘ÔηٿÛÙ·Û˘.

Hesx-1 (Rpx) Î·È ÌÂÙ·ÏÏ¿ÍÂȘ∆Ô ÁÔÓ›‰ÈÔ Hesx-1, Ô˘ ÔÓÔÌ¿˙ÂÙ·È Î·È Rpx

(Rathke’ pouch homeobox gene), Â›Ó·È ÙÔ ÚÒÙÔ·fi Ù· Ù¤ÛÛÂÚ· ÔÌÔÈÔÙÈο ÁÔÓ›‰È· (homeoboxgenes) Ù˘ ˘fiÊ˘Û˘ Ô˘ ÂÎÊÚ¿˙ÂÙ·È Î·Ù¿ ÙˉȿÚÎÂÈ· ÙˆÓ ÚÒÙˆÓ ÛÙ·‰›ˆÓ ·Ó¿Ù˘Í˘ Ù˘ ˘fi-Ê˘Û˘ Î·È ‚Ú›ÛÎÂÙ·È ÛÙÔÓ ¿ÓıÚˆÔ ÛÙÔ ¯ÚˆÌfiÛˆ-Ì· 3 (3p21.2) (67,68).

∏ ·Ô˘Û›· Ù˘ Hesx-1 ÚˆÙ½Ó˘ ÛÙ· ÔÓÙ›ÎÈ·ÈÛÙ‡ÂÙ·È fiÙÈ ÚÔηÏ› ‰È·Ù·Ú·¯¤˜ ÛÙÔ ÎÂÓÙÚÈÎfiÓ¢ÚÈÎfi Û‡ÛÙËÌ· Î·È ‰˘ÛÏ·Û›· Ù˘ ˘fiÊ˘Û˘(69). ¶Ôχ ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ Hesx-1 ·ÓıÚÒÈÓÔ ÁÔÓ›‰ÈÔ ¤¯ÂÈ ·Ó·ÊÂÚı› ÚfiÛÊ·Ù·, ÔÈÔԛ˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ‹ Ì ÂÈ-ÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú·. OÈ ÌÂÙ·ÏÏ¿ÍÂȘ ·˘Ù¤˜ Ê·›-ÓÂÙ·È Ó· Â›Ó·È ˘Â‡ı˘Ó˜ ÁÈ· ¤Ó· ÌÈÎÚfi ÔÛÔÛÙfi·ÛıÂÓÒÓ Ì ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ·, ÂÓÒ ·Ó¢ڛ-ÛÎÔÓÙ·È Î˘Ú›ˆ˜ Û ·ÛıÂÓ›˜ ÌÂ Û˘ÁÁÂÓ‹ ÔÙÈ΋·ÙÚÔÊ›·, fiˆ˜ Ë ‰È·ÊÚ·ÁÌ·ÙÔ-ÔÙÈ΋ ‰˘ÛÏ·Û›·(Û‡Ó‰ÚÔÌÔ Morsier), ηıÒ˜ Î·È Û ·ÛıÂÓ›˜ Ì¢ÔÏ·Û›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘(69,6). ∂ÈÚfiÛıÂÙ·, ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ÌÔÚ› Ó··ÚÔ˘ÛÈ¿ÛÔ˘Ó ÌÂÈÎÙ‹ ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘ ηÈ,ˆ˜ ÂÎ ÙÔ‡ÙÔ˘, Ó· ¯ÚÂÈ¿˙ÔÓÙ·È ıÂڷ›· ˘Ôηٿ-ÛÙ·Û˘ (69).

™˘¯ÓfiÙËÙ· ÁÂÓÂÙÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ Û ·ÛıÂÓ›˜ Ì·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GHD)

OÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ÚÔ·Ó·ÊÂÚfiÌÂÓ· ÁÔÓ›‰È··Ó¢ڛÛÎÔÓÙ·È Û¯ÂÙÈο Û¿ÓÈ·. ∞˘Ùfi Û˘Ì‚·›ÓÂÈ ‰Èfi-ÙÈ ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔÚ¤˜ Ë ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛËÂÊ·ÚÌfi˙ÂÙ·È Û ηıÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ Î·È ÌÂÛ˘ÁÎÂÎÚÈ̤ÓË Î·Ù‡ı˘ÓÛË ¤Ú¢ӷ˜. °È· ÙÔ ÏfiÁÔ·˘Ùfi, ÚÔ˜ ÙÔ ·ÚfiÓ, Ë ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË DNA·Ï¿ ÂȂ‚·ÈÒÓÂÈ ÙË ‰È¿ÁÓˆÛË Ù˘ ·Ó¿ÚÎÂÈ·˜GH, Ë ÔÔ›· Á›ÓÂÙ·È ˆ˜ ÁÓˆÛÙfi ·fi ÙËÓ ÎÏÈÓÈ΋ ÂÈ-ÎfiÓ· Î·È ÙȘ ÁÓˆÛÙ¤˜ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘. ∂Í¿Ï-ÏÔ˘, Ë ·Ó·Ï˘ÙÈ΋ ÂͤٷÛË DNA Â›Ó·È Ì›· ¯ÚÔÓÔ‚fi-Ú· Î·È ·ÎÚÈ‚‹ ̤ıÔ‰Ô˜, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌËÓÌÔÚ›, ÚÔ˜ ÙÔ ·ÚfiÓ, Ó· Á›ÓÂÈ Ì¤ıÔ‰Ô˜ ÚÔ˘Ù›Ó·˜.

™˘¯ÓfiÙËÙ· ÁÂÓÂÙÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ ÛÙË ÌÂÌÔӈ̤ÓË·Ó¿ÚÎÂÈ· (IGHD) Î·È ÔÏÏ·Ï‹ ·Ó¿ÚÎÂÈ· ˘fi-Ê˘Û˘ (CPHD)

∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘GH ÈÛÙ‡ÂÙ·È fiÙÈ Êı¿ÓÂÈ ÂÚ›Ô˘ ÛÙÔ 10% ÙˆÓ

·ÛıÂÓÒÓ Ì ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘(IGHD) (6,17,70). ∞ÓÙ›ÛÙÔȯ·, Ë Û˘¯ÓfiÙËÙ· ÌÂÙ·Ï-Ï¿ÍÂˆÓ ÛÙÔ GHRHR ÁÔÓ›‰ÈÔ Ê·›ÓÂÙ·È Ó· Â›Ó·È ÔχÌÈÎÚfiÙÂÚË. ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ÂÚÈ-ÙÒÛÂˆÓ Ì ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ÔÚÌfiÓ˘ (IGHD) ÂÍ·ÎÔÏÔ˘ı› Ó· ¯·Ú·ÎÙËÚ›˙ÂٷȈ˜ ȉÈÔ·ı‹˜.

∆· ÂÚÈÔÚÈṲ̂ӷ Û˘ÌÂÚ¿ÛÌ·Ù· ÙˆÓ ‰È·ÊfiÚˆÓÌÂÏÂÙÒÓ Û‡Ìʈӷ Ì ÙÔ˘˜ ›‰ÈÔ˘˜ ÂÚ¢ÓËÙ¤˜, ÔÊ›-ÏÔÓÙ·È ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ ·˘Ù¤˜ ÛÙÚ¤ÊÔÓÙ·È Î˘Ú›ˆ˜ÛÙËÓ ˘fiÊ˘ÛË, ÂÓÒ ıˆÚÂ›Ù·È fiÙÈ Ù· 2/3 ÂÚ›Ô˘ÙˆÓ ·ÛıÂÓÒÓ Ì IGHD ¤¯Ô˘Ó ˘Ôı·Ï·ÌÈ΋ Ì¿ÏÏÔÓ,·Ú¿ ˘ÔÊ˘Ûȷ΋ ·ÓˆÌ·Ï›· (6). ™‹ÌÂÚ·, ÈÛÙ‡Â-Ù·È fiÙÈ ÛÙË ÏÂÙ‹ ÂÈÎÔÈÓˆÓ›· ˘Ôı·Ï¿ÌÔ˘-˘fiÊ˘-Û˘ ÂÌϤÎÔÓÙ·È ·Ú¿ÁÔÓÙ˜ ÏÈÁfiÙÂÚÔ ‰È¢ÎÚÈÓÈ-Ṳ̂ÓÔÈ ·fi ÂΛÓÔ˘˜ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙË ‰È·ÊÔÚÔ-Ô›ËÛË Ù˘ ˘fiÊ˘Û˘ (6).

∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, Ë Ù·˘ÙÔÔ›ËÛË ÙˆÓ ·Ú·-ÁfiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors), ÔÈÔÔ›ÔÈ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·Ó¿Ù˘ÍË Î·È ÙË ‰È·ÊÔÚÔ-Ô›ËÛË Ù˘ ˘fiÊ˘Û˘, Ì¿˜ ‚ÔËı¿ Ó· ηٷÓÔ‹ÛÔ˘-Ì ÙËÓ ·ıÔÁ¤ÓÂÛË ÙˆÓ ‰È·ÊÔÚÂÙÈÎÒÓ Ù‡ˆÓ ÔÏ-Ï·Ï‹˜ ·Ó¿ÚÎÂÈ·˜ ˘fiÊ˘Û˘ (CPHD). ™‡ÌʈӷÌ ÙÔ˘˜ Pfaffle Î·È Û˘Ó, ÔÈ ÌÈÛÔ› ·fi ÙÔ˘˜ ·ÛıÂÓ›˜Ì ·Ó¿ÚÎÂÈ· GH, TSH Î·È ÚÔÏ·ÎÙ›Ó˘ ¤¯Ô˘Ó‰È·ÎÚÈÙ¤˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ, ÂÓÒ Ù·2/3 ÙˆÓ ·ÛıÂÓÒÓ Ì ·Ó¿ÚÎÂÈ· GH, TSH, PRL ηÈÁÔÓ·‰ÔÙÚÔÈÓÒÓ ¤¯Ô˘Ó ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ÁÔ-Ó›‰ÈÔ.

OÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Hesx-1 ÁÔÓ›‰ÈÔ, Ô˘ ÂÎÊÚ¿-˙ÔÓÙ·È ÓˆÚ›˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÌÊ¿ÓÈÛ˘ ηȉȷÊÔÚÔÔ›ËÛ˘ Ù˘ ˘fiÊ˘Û˘, Â›Ó·È Ôχ ÂÚÈÔ-ÚÈṲ̂Ó˜ Î·È ˘ÔÏÔÁ›˙ÔÓÙ·È Û ÏÈÁfiÙÂÚÔ ·fi 1%ÙˆÓ ·ÛıÂÓÒÓ Ì CPHD. ∆¤ÏÔ˜, Â›Ó·È ‰‡ÛÎÔÏÔ,ÚÔ˜ ÙÔ ·ÚfiÓ, Ó· ˘ÔÏÔÁÈÛÙ› Ë Û˘¯ÓfiÙËÙ· ÙˆÓLHX3 ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔÓ ¿ÓıÚˆÔ, ÏfiÁˆ ÙÔ˘ Â-ÚÈÔÚÈṲ̂ÓÔ˘ ·ÚÈıÌÔ‡ ÂÚÈÙÒÛˆÓ.

™˘ÌÂÚ¿ÛÌ·Ù·∏ ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˘ÔÊ˘-

Ûȷ΋ ·Ó¿ÚÎÂÈ· ÌÔÚ› Ó· ·Ú¿Û¯ÂÈ ÙË ‰˘Ó·Ùfi-ÙËÙ· ÁÈ· ¤ÁηÈÚË Î·È ÂȉÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ‰ÈfiÙÈ ı·Á›ÓÂÙ·È ·ÓÙÈÏËÙ‹ Ë ÛÔ‚·ÚfiÙËÙ· ÙÔ˘ ÚÔ‚Ï‹Ì·-ÙÔ˜, ηıÒ˜ Î·È ÔÈ ‚Ú·¯˘ÚfiıÂÛ̘ Î·È Ì·ÎÚÔÚfi-ıÂÛ̘ Û˘Ó¤ÂȤ˜ ÙÔ˘. ∂›Û˘, Ë ·Ó·Î¿Ï˘„Ë ÙԢ›‰Ô˘˜ ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÙˆÓ ÁÔÓȉ›ˆÓ Ô˘ ÂÓ¤¯Ô-ÓÙ·È ÛÙÔÓ Û¯ËÌ·ÙÈÛÌfi Î·È ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Úfi-ÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÌÔÚ› Ó· ‰ÒÛÂÈ Ô-χÙÈ̘ ÏËÚÔÊÔڛ˜ Û¯ÂÙÈο Ì ÙÔÓ ÙÚfiÔ ÎÏËÚÔ-ÓÔÌÈÎfiÙËÙ·˜ ÙˆÓ ‰È·ÊfiÚˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘, ÙËÓÚfiÁÓˆÛ‹ ÙÔ˘˜ Î·È ÙËÓ ÂÈÏÔÁ‹ Ù˘ ηٿÏÏËÏ˘ıÂڷ›·˜.

µ¤‚·È·, ı· ··ÈÙËı› ·ÚÎÂÙfi ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·Î·È ¤ÓÙÔÓË ÂÚ¢ÓËÙÈ΋ ÚÔÛ¿ıÂÈ·, ¤ˆ˜ fiÙÔ˘ Ë

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94

‰È¿ÁÓˆÛË (ȉÈÔ·ı‹˜) ·Ó¿ÚÎÂÈ· Ù˘ ·˘ÍËÙÈ΋˜ÔÚÌfiÓ˘ ıˆÚËı› Ì›· ‰È·ÁÓˆÛÙÈ΋ ÔÓÙfiÙËÙ· ÙÔ˘·ÚÂÏıfiÓÙÔ˜.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Lacey KA, Parkin JM. Causes of short stature. A community

study of children in Newcastle upon Tyne. Lancet1974;1:42-45.

2. Vimpani GV, Vimpani AF, Lidgard GP, Cameron EH,Farquhar JW. Prevalence of severe growth hormonedeficiency. Br Med J 1977;2:427-430.

3. Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M.Utah Growth Study: growth standards and the prevalenceof growth hormone deficiency. J Pediatr 1994;125:29-35.

4. Wilton P, Wallstrom A. An overview of the diagnoses in theKabi Pharmacia International Growth Study. Acta PaediatrScand 1991;379 (Suppl):S93-S98.

5. Pfaffle RW, Blankenstein O, Wuller S, Kentrup H. Combinedpituitary hormone deficiency: role of Pit-1 and Prop-1. ActaPaediatr 1999;88 (Suppl):S33-S41.

6. Pfaffle R, Blankenstein O, Wuller S, Heimann K, Heimann G.Idiopathic growth hormone deficiency: a vanishingdiagnosis? Horm Res 2000;53 (Suppl 3):S1-S8.

7. Procter AM, Phillips JA 3rd, Cooper DN. The moleculargenetics of growth hormone deficiency. Hum Genet1998;103:255-272.

8. Parks JS, Brown MR, Hurley DL, Phelps CJ, Wajnrajch MP.Heritable disorders of pituitary development. J ClinEndocrinol Metab 1999;84:4362-4370.

9. Pfaffle RW, Kim C, Blankenstein O, Kentrup H. GHtranscription factors. J Pediatr Endocrinol Metab 1999;12(Suppl 1):S311-S317.

10. Bozzola M, Rognone F, Zecca M, Calligaro A. Developmentof the pituitary and its abnormalities. J Pediatr EndocrinolMetab 1999;12 (Suppl 1):S319-S327.

11. Dasen JS, Rosenfeld MG. Signaling and transcriptionalmechanisms in pituitary development. Annu Rev Neurosci2001;24:327-355.

12. ™Ù˘ÏÈ·ÓÔÔ‡ÏÔ˘ º. µ·ÛÈΤ˜ ·Ú¯¤˜ ÌÔÚȷ΋˜ µÈÔÏÔÁ›·˜.∂ÈÛ·ÁˆÁ‹ ÛÙË ÌÔÚȷ΋ Î·È ÂÚÁ·ÛÙËÚȷ΋ ÂÓ‰ÔÎÚÈÓÔÏÔÁ›·.∞ı‹Ó·: ∂ÏÏËÓÈ΋ ∂Ó‰ÔÎÚÈÓÔÏÔÁÈ΋ ∂Ù·ÈÚ›·; 1995. ÛÂÏ. 21.

13. Wajnrajch MP. Genetic disorders of human growth. JPediatr Endocrinol Metab 2002;15 (Suppl 2):S701-S714.

14. Chen EY, Liao YC, Smith DH, Barrera-Saldana HA, GelinasRE, Seeburg PH. The human growth hormone locus:nucleotide sequence, biology, and evolution. Genomics1989;4:479-497.

15. Phillips JA 3rd, Hjelle BL, Seeburg PH, Zachmann M.Molecular basis for familial isolated growth hormonedeficiency. Proc Natl Acad Sci USA 1981;78:6372-6375.

16. Phillips JA 3rd, Cogan JD. Genetic basis of endocrinedisease. 6. Molecular basis of familial human growthhormone deficiency. J Clin Endocrinol Metab 1994;78:11-16.

17. Wagner JK, Eble A, Hindmarsh PC, Mullis PE. Prevalence ofhuman GH-1 gene alterations in patients with isolatedgrowth hormone deficiency. Pediatr Res 1998;43:105-110.

18. Cogan JD, Phillips JA 3rd, Sakati N, Frisch H, Schober E,

Milner RD. Heterogeneous growth hormone (GH) genemutations in familial GH deficiency. J Clin Endocrinol Metab1993;76:1224-1228.

19. Vnencak-Jones CL, Phillips JA 3rd, Chen EY, Seeburg PH.Molecular basis of human growth hormone gene deletions.Proc Natl Acad Sci USA 1988;85:5615-5619.

20. Ghizzoni L, Duquesnoy P, Torresani T, Vottero A, GoossensM, Bernasconi S. Isolated growth hormone deficiency typeIA associated with a 45-kilobase gene deletion within thehuman growth hormone gene cluster in an Italian family.Pediatr Res 1994;36:654-659.

21. Wang Y, Yu LL, Sheng Q, Meng C, Sun J, Chen SS.Analysis of human growth hormone gene 5’ sequences inisolated growth hormone deficiency patients. J Med Genet1994;31:81-82.

22. Missarelli C, Herrera L, Mericq V, Carvallo P. Two different5’ splice site mutations in the growth hormone genecausing autosomal dominant growth hormone deficiency.Hum Genet 1997;101:113-117.

23. Moseley CT, Mullis PE, Prince MA, Phillips JA 3rd. An exonsplice enhancer mutation causes autosomal dominant GHdeficiency. J Clin Endocrinol Metab 2002;87:847-852.

24. Takahashi I, Takahashi T, Komatsu M, Sato T, Takada G. Anexonic mutation of the GH-1 gene causing familial isolatedgrowth hormone deficiency type II. Clin Genet 2002;61:222-225.

25. Conley ME, Burks AW, Herrod HG, Puck JM. Molecularanalysis of X-linked agammaglobulinemia with growthhormone deficiency. J Pediatr 1991;119:392-397.

26. Ogata T, Petit C, Rappold G, Matsuo N, Matsumoto T,Goodfellow P. Chromosomal localization of apseudoautosomal growth gene(s). J Med Genet1992;29:624-628.

27. Binder G, Ranke MB. Screening for growth hormone (GH)gene splice-site mutations in sporadic cases with severeisolated GH deficiency using ectopic transcript analysis. JClin Endocrinol Metab 1995;80:1247-1252.

28. Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone.Mol Endocrinol 1992;6:1734-1744.

29. Gaylinn BD, Harrison JK, Zysk JR, Lyons CE, Lynch KR,Thorner MO. Molecular cloning and expression of a humananterior pituitary receptor for growth hormone-releasinghormone. Mol Endocrinol 1993;7:77-84.

30. Petersenn S, Rasch AC, Heyens M, Schulte HM. Structureand regulation of the human growth hormone-releasinghormone receptor gene. Mol Endocrinol 1998;12:233-247.

31. Baumann G, Maheshwari H. The Dwarfs of Sindh: severegrowth hormone (GH) deficiency caused by a mutation inthe GH-releasing hormone receptor gene. Acta Paediatr1997;423 (Suppl):S33-S38.

32. Wajnrajch MP, Gertner JM, Harbison MD, Chua SC Jr,Leibel RL. Nonsense mutation in the human growthhormone-releasing hormone receptor causes growth failureanalogous to the little (lit) mouse. Nat Genet 1996;12:88-90.

33. Netchine I, Talon P, Dastot F, Vitaux F, Goossens M,Amselem S. Extensive phenotypic analysis of a family withgrowth hormone (GH) deficiency caused by a mutation inthe GH-releasing hormone receptor gene. J Clin Endocrinol

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·94

¶·È‰È·ÙÚÈ΋ 2003;66:89-96 Paediatriki 2003;66:89-96

95

Metab 1998;83:432-436. 34. Horikawa R. Isolated GH deficiency due to inactivating

mutation of GHRH receptor. Nippon Rinsho 2002;60:297-305.

35. Salvatori R, Aguiar-Oliveira MH, Monte LV, Hedges L,Santos NL, Pereira RM et al. Detection of a recurringmutation in the human growth hormone-releasing hormonereceptor gene. Clin Endocrinol (Oxf) 2002;57:77-80.

36. Salvatori R, Fan X, Mullis PE, Haile A, Levine MA. Decreasedexpression of the GHRH receptor gene due to a mutation ina Pit-1 binding site. Mol Endocrinol 2002;16:450-458.

37. Salvatori R, Hayashida CY, Aguiar-Oliveira MH, Phillips JA3rd, Souza AH, Gondo RG et al. Familial dwarfism due to anovel mutation of the growth hormone-releasing hormonereceptor gene. J Clin Endocrinol Metab 1999;84:917-923.

38. Cohen LE, Zanger K, Brue T, Wondisford FE, Radovick S.Defective retinoic acid regulation of the Pit-1 geneenhancer: a novel mechanism of combined pituitaryhormone deficiency. Mol Endocrinol 1999;13:476-484.

39. Bodner M, Castrillo JL, Theill LE, Deerinck T, Ellisman M,Karin M. The pituitary-specific transcription factor GHF-1 isa homeobox-containing protein. Cell 1988;55:505-518.

40. Raskin S, Cogan JD, Summar ML, Moreno A, KrishnamaniMR, Phillips JA 3rd. Genetic mapping of the humanpituitary-specific transcriptional factor gene and its analysisin familial panhypopituitary dwarfism. Hum Genet1996;98:703-705.

41. Simmons DM, Voss JW, Ingraham HA, Holloway JM, BroideRS, Rosenfeld MG et al. Pituitary cell phenotypes involvecell-specific Pit-1 mRNA translation and synergisticinteractions with other classes of transcription factors.Genes Dev 1990;4:695-711.

42. Mangalam HJ, Albert VR, Ingraham HA, Kapiloff M, WilsonL, Nelson C et al. A pituitary POU domain protein, Pit-1,activates both growth hormone and prolactin promoterstranscriptionally. Genes Dev 1989;3:946-958.

43. Tatsumi K, Miyai K, Notomi T, Kaibe K, Amino N, Mizuno Yet al. Cretinism with combined hormone deficiency causedby a mutation in the PIT1 gene. Nat Genet 1992;1:56-58.

44. Pfaffle RW, DiMattia GE, Parks JS, Brown MR, Wit JM,Jansen M et al. Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science1992;257:1118-1121.

45. Pellegrini-Bouiller I, Belicar P, Barlier A, Gunz G, Charvet JP,Jaquet P et al. A new mutation of the gene encoding thetranscription factor Pit-1 is responsible for combinedpituitary hormone deficiency. J Clin Endocrinol Metab1996;81:2790-2796.

46. Irie Y, Tatsumi K, Ogawa M, Kamijo T, Preeyasombat C,Suprasongsin C et al. A novel E250X mutation of the PIT1gene in a patient with combined pituitary hormonedeficiency. Endocr J 1995;42:351-354.

47. Brown MR, Parks JS, Adess ME, Rich BH, Rosenthal IM,Voss TC et al. Central hypothyroidism reveals compoundheterozygous mutations in the Pit-1 gene. Horm Res1998;49:98-102.

48. Pernasetti F, Milner RD, al Ashwal AA, de Zegher F, ChavezVM, Muller M et al. Pro239Ser: a novel recessive mutation ofthe Pit-1 gene in seven Middle Eastern children with growth

hormone, prolactin, and thyrotropin deficiency. J ClinEndocrinol Metab 1998;83:2079-2083.

49. Okamoto N, Wada Y, Ida S, Koga R, Ozono K, Chiyo H etal. Monoallelic expression of normal mRNA in the PIT1mutation heterozygotes with normal phenotype and biallelicexpression in the abnormal phenotype. Hum Mol Genet1994;3:1565-1568.

50. Radovick S, Nations M, Du Y, Berg LA, Weintraub BD,Wondisford FE. A mutation in the POU-homeodomain ofPit-1 responsible for combined pituitary hormonedeficiency. Science 1992;257:1115-1118.

51. Ohta K, Nobukuni Y, Mitsubuchi H, Fujimoto S, Matsuo N,Inagaki H et al. Mutations in the Pit-1 gene in children withcombined pituitary hormone deficiency. Biochem BiophysRes Commun 1992;189:851-855.

52. Cohen LE, Wondisford FE, Salvatoni A, Maghnie M,Brucker-Davis F, Weintraub BD et al. A “hot spot” in the Pit-1 gene responsible for combined pituitary hormonedeficiency: clinical and molecular correlates. J ClinEndocrinol Metab 1995;80:679-684.

53. Fofanova OV, Takamura N, Kinoshita E, Yoshimoto M, TsujiY, Peterkova VA et al. Rarity of PIT1 involvement in childrenfrom Russia with combined pituitary hormone deficiency.Am J Med Genet 1998;77:360-365.

54. Hendriks-Stegeman BI, Augustijn KD, Bakker B, HolthuizenP, van der Vliet PC, Jansen M. Combined pituitary hormonedeficiency caused by compound heterozygosity for twonovel mutations in the POU domain of the Pit1/POU1F1gene. J Clin Endocrinol Metab 2001;86:1545-1550.

55. Pfaffle R, Kim C, Otten B, Wit JM, Eiholzer U, Heimann G etal. Pit-1: clinical aspects. Horm Res 1996;45 (Suppl 1):S25-S28.

56. Showalter AD, Smith TP, Bennett GL, Sloop KW, WhitsettJA, Rhodes SJ. Differential conservation of transcriptionaldomains of mammalian Prophet of Pit-1 proteins revealedby structural studies of the bovine gene and comparativefunctional analysis of the protein. Gene 2002;291:211-221.

57. Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ,O’Connell SM et al. Pituitary lineage determination by theProphet of Pit-1 homeodomain factor defective in Amesdwarfism. Nature 1996;384:327-333.

58. Duquesnoy P, Roy A, Dastot F, Ghali I, Teinturier C,Netchine I et al. Human Prop-1: cloning, mapping, genomicstructure. Mutations in familial combined pituitary hormonedeficiency. FEBS Lett 1998;437:216-220.

59. Wu W, Cogan JD, Pfaffle RW, Dasen JS, Frisch H,O’Connell SM et al. Mutations in PROP1 cause familialcombined pituitary hormone deficiency. Nat Genet1998;18:147-149.

60. Fofanova O, Takamura N, Kinoshita E, Parks JS, Brown MR,Peterkova VA et al. Compound heterozygous deletion of thePROP-1 gene in children with combined pituitary hormonedeficiency. J Clin Endocrinol Metab 1998;83:2601-2604.

61. Fluck C, Deladoey J, Rutishauser K, Eble A, Marti U, Wu Wet al. Phenotypic variability in familial combined pituitaryhormone deficiency caused by a PROP1 gene mutationresulting in the substitution of Arg�Cys at codon 120(R120C). J Clin Endocrinol Metab 1998;83:3727-3734.

62. Crone J, Pfaffle R, Stobbe H, Prayer D, Gomez I, Frisch H.

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·95

Familial combined pituitary hormone deficiency caused byPROP-1 gene mutation. Growth patterns and ªRπ studies inuntreated subjects. Horm Res 2002;57:120-126.

63. Bach I, Rhodes SJ, Pearse RV 2nd, Heinzel T, Gloss B,Scully KM et al. P-Lim, a LIM homeodomain factor, isexpressed during pituitary organ and cell commitment andsynergizes with Pit-1. Proc Natl Acad Sci USA1995;92:2720-2724.

64. Sheng HZ, Moriyama K, Yamashita T, Li H, Potter SS,Mahon KA et al. Multistep control of pituitaryorganogenesis. Science 1997;278:1809-1812.

65. Netchine I, Sobrier ML, Krude H, Schnabel D, Maghnie M,Marcos E et al. Mutations in LHX3 result in a new syndromerevealed by combined pituitary hormone deficiency. NatGenet 2000;25:182-186.

66. Sloop KW, Parker GE, Hanna KR, Wright HA, Rhodes SJ.LHX3 transcription factor mutations associated withcombined pituitary hormone deficiency impair the activationof pituitary target genes. Gene 2001;265:61-69.

67. Thomas PQ, Johnson BV, Rathjen J, Rathjen PD.Sequence, genomic organization, and expression of the

novel homeobox gene Hesx1. J Biol Chem 1995;270:3869-3875.

68. Hermesz E, Mackem S, Mahon KA. Rpx: a novel anterior-restricted homeobox gene progressively activated in theprechordal plate, anterior neural plate and Rathke’s pouchof the mouse embryo. Development 1996;122:41-52.

69. Dattani MT, Martinez-Barbera JP, Thomas PQ, BrickmanJM, Gupta R, Martensson IL et al. Mutations in thehomeobox gene HESX1/Hesx1 associated with septo-opticdysplasia in human and mouse. Nat Genet 1998;19:125-133.

70. Mullis PE, Akinci A, Kanaka C, Eble A, Brook CG.Prevalence of human growth hormone-1 gene deletionsamong patients with isolated growth hormone deficiencyfrom different populations. Pediatr Res 1992;31:532-534.

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¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ª·Ú›·-™Ù¤ÏÏ· §·Ú›Ô˘ π¤ÚˆÓÔ˜ 13, ∆.∫. 116 34, ¶·ÁÎÚ¿ÙÈ, ∞ı‹Ó·

∏ ÏÂÈÔ΢ÛÙÈ΋ ‰˘ÛÏ·Û›· ÙˆÓ ÓÂÊÚÒÓ Â›Ó·È Û¯ÂÙÈο Û˘-¯Ó‹ ·ÈÙ›· ÓÂÊÚÈ΋˜ Ì¿˙·˜ ÛÙ· ÓÂÔÁÓ¿, ¤¯ÂÈ Î·Ï‹ ÚfiÁÓˆÛË Î·ÈÛ˘Ó‹ıˆ˜ ‰È·ÈÛÙÒÓÂÙ·È ÛÙÔÓ ¤Ó· ÓÂÊÚfi. ∂›Ó·È ·ÁÓÒÛÙÔ˘ ·È-ÙÈÔÏÔÁ›·˜ Î·È Û ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ÙÔÓÂÈÎÚ·ÙÔ‡ÓÙ· ۈ̷ÙÈÎfi ¯·Ú·ÎÙ‹Ú·. ™Â ÔÛÔÛÙfi 10-25%, Ô˘ÁÈ‹˜ ÓÂÊÚfi˜ ·ÚÔ˘ÛÈ¿˙ÂÈ Î˘ÛÙÂÔÔ˘ÚËÙËÚÈ΋ ·ÏÈÓ‰ÚfiÌËÛËηÈ, ÈÔ Û¿ÓÈ·, ˘ÂÏÔ-Ô˘ÚËÙËÚÈ΋ ÛÙ¤ÓˆÛË, ‰ÈÏ·ÛÈ·ÛÌfi ÙÔ˘˘ÂÏÔÎ·Ï˘ÎÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ¤ÎÙÔÔ Ô˘ÚËÙ‹Ú· ‹ Ô˘ÚËÙËÚÔ-΋ÏË.

∏ ÂÌÊ¿ÓÈÛË ·ÌÊÔÙÂÚfiÏ¢Ú˘ ÏÂÈÔ΢ÛÙÈ΋˜ ‰˘ÛÏ·-Û›·˜ Â›Ó·È Û˘Ó‹ıˆ˜ ı·Ó·ÙËÊfiÚÔ˜ ÛÙËÓ ÂÌ‚Ú˘˚΋ ˙ˆ‹ Î·È ‰È·-ÈÛÙÒÓÂÙ·È ÛÙÔ 7-23% ÙˆÓ ·ÛıÂÓÒÓ. ™ÙËÓ ÂÚ›ÙˆÛË Ô˘ Â-ÚÈÁÚ¿ÊÂÙ·È, Ë ·ÛıÂÓ‹˜ Ì ·ÌÊÔÙÂÚfiÏ¢ÚÔ˘˜ ÏÂÈÔ΢ÛÙÈ-ÎÔ‡˜ ÓÂÊÚÔ‡˜ ·ÚÔ˘Û›·˙ ΢ÛÙÈ΋ ‰˘ÛÏ·Û›· ÌfiÓÔ ÛÙÔ ¿ÓˆÙÌ‹Ì· ÙÔ˘ ‰ÂÍÈÔ‡ ÓÂÊÚÔ‡ Ô˘ ‰È·ÈÛÙÒıËÎÂ Î·È ‰ÈÏ·ÛÈ·ÛÌfiÙÔ˘ ˘ÂÏÔÎ·Ï˘ÎÈÎÔ‡ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜. ∏ ·ÛıÂÓ‹˜ ‰ÂÓ ·ÚÔ˘-

Û›·˙ ÙËÓ ÎÏËÚÔÓÔÌÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘, ÁÈ·Ù› Î·È ÔÈ ‰‡Ô ÁÔ-Ó›˜ ·ÚÔ˘Û›·˙·Ó Ê˘ÛÈÔÏÔÁÈÎfi ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÓÂÊÚÒÓ.™ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË, Ë ·ÛıÂÓ‹˜ ‰È·ÙËÚÔ‡ÛÂ Ê˘ÛÈÔÏÔÁÈ΋ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, fï˜ Ë ÚfiÁÓˆÛË Â›Ó·È ÂÈÊ˘Ï·ÎÙÈ΋ Ïfi-Áˆ Ù˘ ÛËÌ·ÓÙÈ΋˜ ÂÏ¿ÙÙˆÛ˘ Ù˘ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÓÂÊÚÈ΋˜ Ì¿-˙·˜ Ù˘ ·ÛıÂÓÔ‡˜ Î·È ÙȘ ‚Ï¿‚˜ Ô˘ Èı·ÓÒ˜ ı· ÚÔ·„Ô˘ÓÛÙÔ Ì¤ÏÏÔÓ ·fi ÙËÓ ·˘ÍË̤ÓË ÛÂÈÚ·Ì·ÙÈ΋ ˘ÂډȋıËÛË.

∞ÌÊÔÙÂÚfiÏ¢ÚÔÈ ÏÂÈÔ΢ÛÙÈÎÔ› ÓÂÊÚÔ› - ¤Ó· ·Û˘Ó‹ıÈÛÙÔ ÂÚÈÛÙ·ÙÈÎfi1

¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›·

1Agrawal L, Millard ML, Fairhurst J, Gilbert RD Bilateral multicystic kidneys - an unusual case Pediatr Nephrol 2002;17:964-965

™ÙÂÊ·Ó›‰Ë˜ ∫. π. ∞Ó·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜ ¡ÂÊÚÔÏÔÁÈÎÔ‡ ∆Ì‹Ì·ÙÔ˜ ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·96

¶·È‰È·ÙÚÈ΋ 2003;66:97-103 Paediatriki 2003;66:97-103

97

™‡Ó‰ÚÔÌ· ÙÔÍÈ΋˜ ηٷÏËÍ›·˜ ÛÙ· ·È‰È¿ °. ™È‰¤ÚË, ∞. µ·ÛÈÏfiÔ˘ÏÔ˜

Toxic shock syndromes G. Sideri, A. Vassilopoulos

∞¡∞™∫O¶∏™∏ REVIEW ARTICLE

ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ ¶·È‰ÈÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·

Paediatric Intensive Care Unit, “P. & A. Kyriakou” Children’s Hospital, Athens

�¶ÂÚ›ÏË„Ë: ∆Ô Û‡Ó‰ÚÔÌÔ ÙÔÍÈ΋˜ ηٷÏËÍ›·˜(TSS) ·ÔÙÂÏ› Ì›· Û¿ÓÈ·, ·ÏÏ¿ Ôχ ‚·ÚÈ¿ ÎÏÈÓÈ-΋ ÔÓÙfiÙËÙ· ÛÙ· ·È‰È¿. OÈ ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿-ÛÂȘ Ô˘ ÙÔ ÚÔηÏÔ‡Ó Â›Ó·È ÔÍ›˜ ÔÏ˘Û˘ÛÙËÌ·-ÙÈΤ˜ ‰È·Ù·Ú·¯¤˜, Ô˘ Û˘Óԉ‡ÔÓÙ·È ·fi Ïԛ̈ÍË‹ ·ÔÈÎÈÛÌfi Ì ÛÙÂϤ¯Ë Staphylococcus aureus ‹Streptococcus pyogenes, Ù· ÔÔ›· ·Ú¿ÁÔ˘Ó Â͈-ÙÔ͛Ә ÈηӤ˜ Ó· ‰Ú¿ÛÔ˘Ó Û·Ó ˘ÂÚ·ÓÙÈÁfiÓ·. ¶·-Ú¿ ÙÔÓ ÎÏÈÓÈÎfi ‰È·¯ˆÚÈÛÌfi ÙÔ˘ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎÔ‡TSS ·fi ÙÔ ÛÙÚÂÙÔÎÔÎÎÈÎfi TSS, Ô ·ıÔÁÂÓÂÙÈÎfi˜Ì˯·ÓÈÛÌfi˜ ıˆÚÂ›Ù·È fiÙÈ Â›Ó·È Ô ›‰ÈÔ˜. ∏ ˘ÂÚ·-ÓÙÈÁÔÓÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ·ÂÏ¢ı¤ÚˆÛË ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ, ˉڿÛË ÙˆÓ ÔÔ›ˆÓ ÚÔηÏ› ÙȘ Û˘ÛÙËÌ·ÙÈΤ˜ ·-ıÔÊ˘ÛÈÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ (˘fi-Ù·ÛË, ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·). ∆Ô Û‡Ó‰ÚÔÌÔ¯·Ú·ÎÙËÚ›˙ÂÙ·È ÎÏÈÓÈο ·fi ˘ÚÂÙfi, ‰È¿¯˘ÙÔ ÎËÏÈ-‰Ò‰Â˜ ÂÍ¿ÓıËÌ·, ˘fiÙ·ÛË Î·È ÔÏ˘ÔÚÁ·ÓÈ΋ ·ÓÂ-¿ÚÎÂÈ·. °È· ÙËÓ ÂÈÙ˘¯‹ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘Ó-‰ÚfiÌÔ˘ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ·›˙ÂÈ Ë ·ÓÙÈÌÈÎÚԂȷ΋·ÁˆÁ‹, ·ÏÏ¿ ΢ڛˆ˜ Ë ¤ÁηÈÚË ·ÓÙÈÌÂÙÒÈÛË ÙË˜Î˘ÎÏÔÊÔÚÈ΋˜ ηٷÏËÍ›·˜, Ë ‰È·Ù‹ÚËÛË ÈηÓÔÔÈ-ËÙÈ΋˜ ηډȷ΋˜ ·ÚÔ¯‹˜ (¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ, ÈÓÔ-ÙÚfiˆÓ) Î·È Ë ·ÔηٿÛÙ·ÛË ÙˆÓ ‰È·Ù·Ú·¯ÒÓÔÌÔÈfiÛÙ·Û˘.

§¤ÍÂȘ ÎÏÂȉȿ: Û‡Ó‰ÚÔÌ· ÙÔÍÈ΋˜ ηٷÏËÍ›·˜,ÛÙÚÂÙÔÎÔÎÎÈÎfi ÙÔÍÈÎfi Û‡Ó‰ÚÔÌÔ, ÛÙ·Ê˘ÏÔÎÔÎÎÈ-Îfi ÙÔÍÈÎfi Û‡Ó‰ÚÔÌÔ, ÙÔÍ›ÓË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ù˘ ÙÔ-ÍÈ΋˜ ηٷÏËÍ›·˜.

�Abstract: The toxic shock syndrome (TSS) is anuncommon but severe clinical problem in children.The pathological conditions that precipitate thissyndrome are acute multisystem disorders,associated with infection/colonization by strains ofStaphylococcus aureus or Streptococcus pyogenes(and rarely other streptococcal species) whichproduce exotoxins capable of acting assuperantigens. Although clinically distinct,staphylococcal and streptococcal types of TSS arebelieved to share this common pathogeneticmechanism. Superantigen activity results in amassive release of proinflammatory cytokineswhich cause multisystem disorders. Clinically thesyndrome is characterized by fever, hypotension,erythroderma, and multisystem failure. Thesuccessful management of TSS is based on theadministration of appropriate antibiotic agents, butprimarily on the timely management of circulatoryshock (fluid balance, use of inotropic agents) andthe conservation of adequate cardiac output).

Key words: toxic shock syndrome, streptococcaltoxic shock syndrome, staphylococcal toxic shocksyndrome, toxic shock syndrome toxin-1.

™˘ÓÙÔÌÔÁڷʛ˜TSS Toxic shock syndrome TSST-1 Toxic shock syndrome toxin-1 TNF Tumor necrosis factor IL-1 Interleukin 1

TCR T-cell receptor CPK ∫Ú·ÙÈÓÈ΋ ʈÛʈÎÈÓ¿ÛË ¢∂™ ¢ÈÎÙ˘ÔÂÓ‰ÔıËÏÈ·Îfi Û‡ÛÙËÌ· ∞ª¶ ∞ÈÌÔÂÙ¿ÏÈ·

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·97

∂ÈÛ·ÁˆÁ‹ ∆· Û‡Ó‰ÚÔÌ· ÙÔÍÈ΋˜ ηٷÏËÍ›·˜ ÛÙ· ·È‰È¿

Â›Ó·È ‚·ÚȤ˜ ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ, ÔÈ Ôԛ˜ÌÔÚÔ‡Ó Ó· ı¤ÛÔ˘Ó Û ΛӉ˘ÓÔ ÙË ˙ˆ‹ ÙÔ˘ ¿Û¯Ô-ÓÙÔ˜ ·È‰ÈÔ‡. ø˜ ·ıÔÏÔÁÈΤ˜ ÔÓÙfiÙËÙ˜ ¤¯Ô˘Ó·Ó·ÁÓˆÚÈÛÙ› Î·È ÂÚÈÁÚ·Ê› ÙËÓ ÙÂÏÂ˘Ù·›· 25ÂÙ›·Î·È ¤¯Ô˘Ó Ù‡¯ÂÈ ¤ÓÙÔÓ˘ ÌÂϤÙ˘. ªÔÏÔÓfiÙÈ Û¿-ÓȘ ÛÙ· ·È‰È¿, ı· Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·ÈÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙˆÓ ÙÔÍÈÎÒÓ ÂÍ·ÓıËÌ·ÙÈ-ÎÒÓ ÓfiÛˆÓ, Ô˘ ÌÔÚÔ‡Ó Ó· Á›ÓÔ˘Ó ·ÂÈÏËÙÈΤ˜ ÁÈ·ÙË ˙ˆ‹ (ÔÛÙÚ·ÎÈ¿, ÙÔÍÈ΋ ÂȉÂÚÌÔÓÂÎÚfiÏ˘ÛË, Û‡Ó-‰ÚÔÌÔ Kawasaki, ÏÂÙÔÛ›ڈÛË, Û‡Ó‰ÚÔÌÔStevens-Johnson).

∂ΉËÏÒÓÔÓÙ·È Ôͤˆ˜ Ì ‚·ÚÈ¿ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ηÈÛ˘Óԉ‡ÔÓÙ·È ·fi Ïԛ̈ÍË/·ÔÈÎÈÛÌfi Ì ÛÙÂϤ¯ËStaphylococcus aureus ‹ Streptococcus pyogenes. ∏Â͈ÙÔÍ›ÓË Ô˘ ·Ú¿ÁÔ˘Ó Â›Ó·È Ô Î˘ÚÈfiÙÂÚÔ˜ ÌÂÛÔÏ·-‚ËÙ‹˜ ÁÈ· ÙËÓ ÚfiÎÏËÛË ÙˆÓ ÔÏ˘Û˘ÛÙËÌ·ÙÈÎÒÓ ‰È·-Ù·Ú·¯ÒÓ Ô˘ ÚÔηÏÔ‡Ó Ù· Û‡Ó‰ÚÔÌ·.

∆Ô ÛÙ·Ê˘ÏÔÎÔÎÎÈÎfi TSS ÂÚÈÁÚ¿ÊËΠÁÈ· ÚÒ-ÙË ÊÔÚ¿ ÙÔ 1978, ÂÓÒ ÙÔ ÛÙÚÂÙÔÎÔÎÎÈÎfi TSS ÙÔ1989. ¶·Ú¿ ÙÔÓ ÎÏÈÓÈÎfi ‰È·¯ˆÚÈÛÌfi, Ô ·ıÔÁÂÓÂÙÈ-Îfi˜ Ì˯·ÓÈÛÌfi˜ Â›Ó·È Ô ›‰ÈÔ˜.

™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· ÙÂÏ¢-Ù·›· ‰Â‰Ô̤ӷ Û fi,ÙÈ ·ÊÔÚ¿ ÛÙËÓ ·ıÔÁ¤ÓÂÈ·, ÙȘ·ıÔÊ˘ÛÈÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜, Ù· ‰È·ÁÓˆÛÙÈο ÎÚÈ-Ù‹ÚÈ· Î·È ÙË ıÂڷ›· ÙˆÓ ‰‡Ô Û˘Ó‰ÚfïÓ.

™Ù·Ê˘ÏÔÎÔÎÎÈÎfi TSS ∂ȉËÌÈÔÏÔÁ›·∞Ú¯Èο, ‰fiıËΠÌÂÁ·Ï‡ÙÂÚË ÚÔÛÔ¯‹ ÛÙË Û¯¤-

ÛË ÙÔ˘ staph-TSS Ì ÙËÓ ¤ÌÌËÓÔ Ú‡ÛË Î·È ÙË ¯Ú‹-ÛË ·ÔÚÚÔÊËÙÈÎÔ‡ tampon Û Ӥ˜ Á˘Ó·›Î˜. ªfi-ÓÔ ÙÔ 50% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÙÔ˘ staph-TSS ÚÔ-ηÏÂ›Ù·È Î¿Ùˆ ·fi ·˘Ù¤˜ ÙȘ Û˘Óı‹Î˜ (1), ÂÓÒ ÔÈ˘fiÏÔȘ ÂÚÈÙÒÛÂȘ Û˘Ó‰˘¿˙ÔÓÙ·È Ì ¯ÂÈÚÔ˘Ú-ÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ, ÂÁη‡Ì·Ù·, ÙÔÎÂÙÔ‡˜, ÏÔÈÌÒÍÂȘ̷ϷÎÒÓ ÌÔÚ›ˆÓ Î·È ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡(2). °È· ¿ÁÓˆÛÙÔ˘˜ ÏfiÁÔ˘˜, ÙÔ staph-TSS ›ӷÈÛ¿ÓÈÔ Û ·È‰È¿ ËÏÈΛ·˜ <10 ÂÙÒÓ. ¶·Ú’ fiÏ· ·˘-Ù¿, Ô ·ÔÈÎÈÛÌfi˜ ·fi ÛÙ·Ê˘ÏfiÎÔÎÎÔ ¯Ú˘Û›˙ÔÓÙ·Ô˘ ·Ú¿ÁÂÈ ÙÔ͛Ә Â›Ó·È Û˘¯Ófi˜, fiˆ˜ ›Û˘,Û˘¯Ó‹ Â›Ó·È Î·È Ë ÔÚÔ·ÚÓËÙÈÎfiÙËÙ· ÁÈ· ÂȉÈο ·ÓÙÈ-ÛÒÌ·Ù·.

¶·ıÔÁ¤ÓÂÈ·°È· ÙËÓ ·Ó¿Ù˘ÍË ÙÔ˘ staph-TSS ÚÔ··ÈÙ›ٷÈ

·ÔÈÎÈÛÌfi˜ Ì Û٤ϯԘ ÙÔ˘ S. aureus, ÙÔ ÔÔ›Ô·Ú¿ÁÂÈ ÙÔÍ›ÓË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÙÔÍÈ΋˜ ηٷÏË-Í›·˜ (TSST-1) ‹, ÏÈÁfiÙÂÚÔ Û˘¯Ó¿, Ì›· ‹ ÂÚÈÛÛfiÙÂ-Ú˜ ÛÙ·Ê˘ÏÔÎÔÎÎÈΤ˜ ÂÓÙÂÚÔÙÔ͛Ә (SE, A, B, C,D, E) (3), ÔÈ Ôԛ˜ ‰ÚÔ˘Ó Û·Ó ˘ÂÚ·ÓÙÈÁfiÓ·.

∆· ˘ÂÚ·ÓÙÈÁfiÓ· (superantigens) Â›Ó·È Ì›· Û¯Â-ÙÈο ÚfiÛÊ·Ù· ·Ó·ÁÓˆÚÈṲ̂ÓË ÔÌ¿‰· ·ÓÙÈÁÔÓÈÎÒÓÌÔÚ›ˆÓ, Ù· ÔÔ›· Ê·›ÓÂÙ·È fiÙÈ ÚÔηÏÔ‡Ó ‹ ÚÔ¿-

ÁÔ˘Ó ‚Ï¿‚˜ Ì ‰È¿ÊÔÚÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜. ŒÙÛÈ,ÌÔÚÔ‡Ó Ó· ‰ÈÂÁ›ÚÔ˘Ó ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÌÂÁ¿-ÏÔ˘ ·ÚÈıÌÔ‡ ∆-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ, ̤ۈ ‰È·Û‡Ó‰Â-Û˘ Ù˘ V ÂÚÈÔ¯‹˜ Ù˘ ‚ ·Ï˘Û›‰·˜ ÙÔ˘ ˘Ô‰Ô¯¤·ÙÔ˘ ∆ ΢ÙÙ¿ÚÔ˘ TCR (13) Ì ٷ ÌfiÚÈ· ÙÔ˘ Ì›˙ÔÓÔ˜Û˘ÌϤÁÌ·ÙÔ˜ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜ MHC-II. ¢È·Ê¤-ÚÔ˘Ó ·fi Ù· ÎÏ·ÛÈο ·ÓÙÈÁfiÓ· ÛÙÔ fiÙÈ ¤¯Ô˘Ó ÙËÓÈηÓfiÙËÙ· Ó· ÂÓÂÚÁÔÔÈÔ‡Ó ¤Ó· ÌÂÁ¿ÏÔ ÔÛÔÛÙfi∆-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ (5-30%) Û ۯ¤ÛË Ì ٷ Û˘Ì‚·-ÙÈο ·ÓÙÈÁfiÓ· (0,0001-0,01%). ∏ ˘ÂÚ·ÓÙÈÁÔÓÈ΋‰Ú·ÛÙËÚÈfiÙËÙ· ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË Ì·˙È΋ ·Â-Ï¢ı¤ÚˆÛË ÙˆÓ ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ·fi ·ÙÙ·Ú· Ô˘ ÂÎÚÔÛˆÔ‡Ó ·ÓÙÈÁfiÓ· (IL-1,TNF-a) Î·È ·fi Ù· ÏÂÌÊÔ·ÙÙ·Ú· (IL-2, TNF-‚,Interferon-a). ¢ÂÓ ·ÚΛ, fï˜, ÌfiÓÔ Ë ·ÚÔ˘Û›·Ù˘ ÙÔ͛Ӣ Ô˘ ·Ú¿ÁÂÈ ÙÔ Û٤ϯԘ ÙÔ˘ S. aureusÁÈ· Ó· ÚÔηϤÛÂÈ staph-TSS, ·Ó Ï¿‚Ô˘Ì ˘’ fi„ÈÓfiÙÈ Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÓıÚÒˆÓ Ô˘ Â›Ó·È ·ÔÈÎÈ-Ṳ̂ÓÔÈ ‹ ÓÔÛÔ‡Ó ·fi ·˘Ù¿ Ù· ÛÙÂϤ¯Ë ‰ÂÓ ·Ó·-Ù‡ÛÛÔ˘Ó ÔÙ¤ Ïԛ̈ÍË ÌfiÓÔ ·fi ÙË ÌÂÛÔÏ¿‚ËÛËÙ˘ ÙÔ͛Ӣ. °È· ·Ú¿‰ÂÈÁÌ·, Ô S. aureus Ô˘ ÌÂ-ٷʤÚÂÈ TSST-1 ÁÔÓ›‰ÈÔ, ·ÚÔ˘ÛÈ¿˙ÂÙ·È Û ÔÛÔ-ÛÙfi 1-5% ÛÙȘ ÎÔÏÈΤ˜ ηÏÏȤÚÁÂȘ ÙˆÓ Á˘Ó·ÈÎÒÓÎ·È Û ÔÛÔÛÙfi 18% ÛÙȘ ÚÈÓÈΤ˜ ηÏÏȤÚÁÂȘ ·È-‰ÈÒÓ Ô˘ ÓÔÛËχÔÓÙ·È Û ÓÔÛÔÎÔÌÂ›Ô (4). ∂›Û˘,ÔÛÔÛÙfi 1-4% ÙˆÓ ˘ÁÈÒÓ ·ÙfiÌˆÓ Â›Ó·È ·ÔÈÎÈṲ̂ÓÔÌ S. aureus ÈηÓfi Ó· ·Ú¿ÁÂÈ TSST-1 (5).

ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ì›· ÛÂÈÚ¿ ·Ú·ÁfiÓÙˆÓ Û˘Ì‚¿ÏÏÂÈÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙÔ˘ staph-TSS. ∆¤ÙÔÈÔÈ ·Ú¿ÁÔ-ÓÙ˜, ¤Ú·Ó ÙÔ˘ ·ÔÈÎÈÛÌÔ‡ ‹ Ù˘ Ïԛ̈͢ ·fi¯Ú˘Û›˙ÔÓÙ· ÛÙ·Ê˘ÏfiÎÔÎÎÔ Ô˘ ·Ú¿ÁÂÈ ÙÔ͛Ә, ›-Ó·È ÔÈ ·ÂÚfi‚Ș Û˘Óı‹Î˜, ÙÔ Ô˘‰¤ÙÂÚÔ pH, Ë ıÂÚ-ÌÔÎÚ·Û›· 37-40ÔC, Ë ¤ÏÏÂÈ„Ë Mg, Ë ÂÚ›ÛÛÂÈ· Úˆ-ÙÂ˚ÓÒÓ Î·È, Ù¤ÏÔ˜, Ë ·Ô˘Û›· ÚÔÛٷ٢ÙÈÎÔ‡ ·ÓÙÈ-ÛÒÌ·ÙÔ˜ ¤Ó·ÓÙÈ Ù˘ ÂȉÈ΋˜ ÙÔ͛Ӣ. ∏ ·Ô˘Û›· ·ÓÔ-Û›·˜ ÔÊ›ÏÂÙ·È ÛÙËÓ ¤ÏÏÂÈ„Ë ÚÔËÁÔ‡ÌÂÓ˘ ¤ÎıÂ-Û˘ ‹ ÛÙËÓ ·‰˘Ó·Ì›· ·Ú·ÁˆÁ‹˜ ·˘ÙÒÓ ÙˆÓ ·ÓÙÈ-ۈ̿وÓ. O Ù›ÙÏÔ˜ ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘TSST-1 ·˘Í¿ÓÂÈ Ì ÙËÓ ËÏÈΛ·. ŒÙÛÈ ÂÍËÁÂ›Ù·È ÁÈ·Ù›ÚÔÛ‚¿ÏÏÔÓÙ·È Û˘¯ÓfiÙÂÚ· ·È‰È¿ ÌÈÎÚ‹˜ ËÏÈΛ·˜.

™‡Ìʈӷ Ì ÙÔ˘˜ Vergeront Î·È Û˘Ó (16), ÌfiÓÔÙÔ 30% ˘ÁÈÒÓ ·È‰ÈÒÓ ËÏÈΛ·˜ 1-2 ÂÙÒÓ Â›¯Â ÚÔ-Ûٷ٢ÙÈÎÔ‡˜ Ù›ÙÏÔ˘˜ ·ÓÙÈÛˆÌ¿ÙˆÓ (>1:100) ¤Ó·-ÓÙÈ Ù˘ TSST-1. ∞ÓÙ›ıÂÙ·, Û‡Ìʈӷ Ì ÙË ÌÂϤÙËÙˆÓ Notermans Î·È Û˘Ó (17), ÙÔ ·ÓÙ›ÛÙÔÈ¯Ô ÔÛÔ-ÛÙfi ·ÓÙÈÛˆÌ¿ÙˆÓ ÛÙÔ˘˜ ÂÓ‹ÏÈΘ ¤Êı·Ó ÙÔ 90%.£· Ú¤ÂÈ Ó· ÛËÌÂȈı›, ›Û˘, fiÙÈ Ù· ÌËÙÚÈο·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ TSST-1 ·ÓȯÓ‡ÔÓÙ·È Ì¤¯ÚÈÙËÓ ËÏÈΛ· ÙˆÓ 9 ÌËÓÒÓ.

∆Ô 1980, ÔÈ Schlievert Î·È Û˘Ó (15) Ù·˘ÙÔÔ›Ë-Û·Ó Ì›· Â͈ÙÔÍ›ÓË Ô˘ ·›˙ÂÈ ÚˆÙ‡ÔÓÙ· ÚfiÏÔÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘, Ë ÔÔ›· ÔÓÔÌ¿-ÛÙËΠTSST-1. ∏ TSST-1 ¤¯ÂÈ ˘ÚÂÙÔÁfiÓÔ ‰Ú¿ÛË,·˘Í¿ÓÂÈ ÙËÓ ˘ÂÚ¢·ÈÛıËÛ›· ÂÈ‚Ú·‰˘ÓfiÌÂÓÔ˘

¶·È‰È·ÙÚÈ΋ 2003;66:97-103 Paediatriki 2003;66:97-103

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¶·È‰È·ÙÚÈ΋ 2003;66:97-103 Paediatriki 2003;66:97-103

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Ù‡Ô˘ Î·È ÚÔηÏ› ηٷÛÙÔÏ‹ Ù˘ Û‡ÓıÂÛ˘ ·ÓÔ-ÛÔÛÊ·ÈÚÈÓÒÓ, Ù˘ ¯ËÌÂÈÔÙ·Í›·˜ ÙˆÓ ÔÏ˘ÌÔÚÊÔ-‡ÚËÓˆÓ Î·È ÙÔ˘ ¢∂™.

¶·ıÔÊ˘ÛÈÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÛÙÔ TSS∆Ô Û‡Ó‰ÚÔÌÔ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi:

1. ÙË ÁÚ‹ÁÔÚË ÂΉ‹ÏˆÛË Î·È ÂͤÏÈÍË Ù˘ ÓfiÛÔ˘. 2. ·ÈÌÔ‰˘Ó·ÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ì ٷ¯Â›· ÂÁηٿ-ÛÙ·ÛË ˘fiÙ·Û˘, Ô˘ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓÈÛÙÈ΋ ÈÛ¯·ÈÌ›· Î·È ÙËÓ ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·.∏ ˘fiÙ·ÛË Â›Ó·È ·ÔÙ¤ÏÂÛÌ· Ù˘ ·ÏÏËÏ›‰Ú·Û˘ÙÔÍÈÎÒÓ ÌÂÙ·‚È‚·ÛÙÒÓ (΢ÙÔÎÈÓÒÓ, Ï¢ÎÔÙÚÈÂÓÒÓ,ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ, Û˘ÌÏËÚÒÌ·ÙÔ˜, ÔÍÂȉ›Ô˘ ÙÔ˘·˙ÒÙÔ˘, ·ÈÌÔÂÙ·Ï›ˆÓ, Ô˘‰ÂÙÂÚfiÊÈÏˆÓ Î·È ÂÓ‰Ô-ıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ) ·Ú·ÁfiÓÙˆÓ Ô˘ Ô‰ËÁÔ‡Ó ÛÂÂÎÙÂٷ̤ÓË ÂÓ‰ÔıËÏȷ΋ ‚Ï¿‚Ë ÌÂ Û˘Ó¤ÂÈ·: i)ÂÏ¿ÙÙˆÛË ÙÔ˘ ÙfiÓÔ˘ ÙˆÓ ·ÁÁ›ˆÓ (Ì›ˆÛË ÙˆÓ Â-ÚÈÊÂÚÈÎÒÓ ·ÁÁÂÈ·ÎÒÓ ·ÓÙÈÛÙ¿ÛˆÓ) Î·È Ï›ÌÓ·ÛËÙÔ˘ ·›Ì·ÙÔ˜ ÛÙ· ÂÚÈÊÂÚÈο ·ÁÁ›· Î·È ii) ·˘ÍË̤-ÓË ‰È·ÂÚ·ÙfiÙËÙ· Ù˘ ΢ÙÙ·ÚÈ΋˜ ÌÂÌ‚Ú¿Ó˘ Î·È‰È·Ê˘Á‹ ˘ÁÚÒÓ Ì ˘„ËÏ‹ ÂÚÈÂÎÙÈÎfiÙËÙ· ۠χ-Έ̷ ·fi ÙÔÓ ÂÓ‰·ÁÁÂÈ·Îfi ÛÙÔ ‰È¿ÌÂÛÔ ¯ÒÚÔ. 3. ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·, Ë ÔÔ›· Â›Ó·È ·ÔÙ¤-ÏÂÛÌ· Ù˘ ‰Ú¿Û˘ ‰‡Ô ·Ú·ÁfiÓÙˆÓ: i) Ù˘ ·Â˘-ı›·˜ ‰Ú¿Û˘ Ù˘ ÙÔ͛Ӣ Î·È ÙˆÓ ÌÂÙ·‚È‚·ÛÙÒÓÛÙ· ·ÙÙ·Ú· Î·È ii) Ù˘ ÈÛÙÈ΋˜ ÈÛ¯·ÈÌ›·˜, Ô˘ ·Ú¯È-ο ÔÊ›ÏÂÙ·È ÛÙÔÓ ¯·ÌËÏfi ÙfiÓÔ ÙˆÓ ·ÁÁ›ˆÓ ηÈÛÙÔ ÂÎÙÂٷ̤ÓÔ ‰È¿ÌÂÛÔ Ô›‰ËÌ· Ô˘ Û˘ÌȤ˙ÂÈ Î·ÈÚÔηÏ› ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÁÁ›ˆÓ.

·. ∏ ÁÂÓÈÎÂ˘Ì¤ÓË Ì˘·ÏÁ›· Î·È Ë Ì˘˚΋ ·‰˘Ó·Ì›·Ô˘ Û˘Óԉ‡ÔÓÙ·È ·fi ·˘ÍË̤ӷ ›‰·CPK ÛÙÔÓ ÔÚfi, Â›Ó·È ÌÂٷ͇ ÙˆÓ ÚÒÈÌˆÓ Î·ÈÛ˘¯Ó¿ ÈÔ ÂÒ‰˘ÓˆÓ Î·È ·Ú·ÙÂÙ·Ì¤ÓˆÓ ÂÎ-‰ËÏÒÛÂˆÓ ÙÔ˘ TSS. ¶Èı·Ófiٷٷ, Â›Ó·È ·ÔÙ¤-ÏÂÛÌ· Ù˘ ‰Ú¿Û˘ ÙˆÓ IL-1 Î·È TNF. ∫·È ÔÈ ‰‡ÔÚÔηÏÔ‡Ó ÚˆÙÂfiÏ˘ÛË Î·È ·ÂÏ¢ı¤ÚˆÛËÚÔÛÙ·ÁÏ·Ó‰›Ó˘ ∂2, Ô˘ Â›Ó·È ÈÛ¯˘Úfi˜ ‰ÈÂ-Á¤ÚÙ˘ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ fi-ÓÔ˘.

‚. ∏ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ÙÔ˘ TSS ÂΉËÏÒÓÂÙ·È ÌÂÔÓÔΤʷÏÔ, Û‡Á¯˘ÛË, ·ÔÚÔÛ·Ó·ÙÔÏÈÛÌfiÎ·È Û·ÛÌÔ‡˜ Î·È ÔÊ›ÏÂÙ·È ÛÙÔ ÂÎÙÂٷ̤ÓÔÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ·.

Á. ∏ ÂÎÎÚÈÙÈ΋, Û˘¯Ó¿ ¿ÊıÔÓË, ‰È¿ÚÚÔÈ· ˘¿Ú¯ÂÈۯ‰fiÓ Û fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜. ∂ÌÊ·Ó›˙ÂÙ·ÈÌ ÙËÓ ÂΉ‹ÏˆÛË Ù˘ ÓfiÛÔ˘ Î·È Û˘¯Ó¿ ˘¿Ú¯ÂÈ·ÎÚ¿ÙÂÈ· ηٿ ÙËÓ ·È¯Ì‹. ∂›Ó·È ÙÔ ·ÔÙ¤ÏÂÛÌ·Ù˘ ÂÓÙÂÚÔÙÔÍÈ΋˜ ‰Ú¿Û˘ ÛÙÔ TSS.

‰. ¶Ó¢ÌÔÓÈ΋ ÂÌÏÔ΋ ·Ú¯Èο ÌÔÚ› Ó· ÌËÓ˘¿Ú¯ÂÈ, fï˜ ηٿ ÙË ¯ÔÚ‹ÁËÛË ÙˆÓ ˘ÁÚÒÓ·Ó·Ï‹ÚˆÛ˘, ÏfiÁˆ Ù˘ ÙÚȯÔÂȉÈ΋˜ ‰È·Ê˘-Á‹˜, ÂÌÊ·Ó›˙ÔÓÙ·È ÁÚ‹ÁÔÚ· ARDS Î·È Ï¢ÚÈ-ÙÈ΋ Û˘ÏÏÔÁ‹.

Â. ∏ ÔÍ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Â›Ó·È Û˘Ó‹ı˘ ÂÎ-‰‹ÏˆÛË Î·È Â›Ó·È ÓÂÊÚÈ΋˜ Î·È ÚÔ-ÓÂÊÚÈ΋˜

·ÈÙÈÔÏÔÁ›·˜. °›ÓÂÙ·È Ôχ ÛÔ‚·Úfi Úfi‚ÏË̷ηٿ ÙË Ê¿ÛË ¯ÔÚ‹ÁËÛ˘ ÙˆÓ ˘ÁÚÒÓ ·Ó·Ï‹-ÚˆÛ˘.

ÛÙ. ∏ ¤ÎÙˆÛË Ù˘ ηډȷ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ (Ì˘Ô-ηډÈÔ¿ıÂÈ·) Â›Ó·È Û˘¯Ó‹. OÊ›ÏÂÙ·È ÛÙËÓÙÚȯÔÂȉÈ΋ ‰È·Ê˘Á‹, ÛÙË Û˘ÌÊfiÚËÛË ÙÔ˘ ·Á-ÁÂÈ·ÎÔ‡ ‰ÈÎÙ‡Ô˘ ÙˆÓ ÈÛÙÒÓ, ÛÙÔ ‰È¿ÌÂÛÔ Ô›‰Ë-Ì· Î·È ÛÙËÓ ÂÚÈ·ÁÁÂȷ΋ ÊÏÂÁÌÔÓÒ‰Ë ‰È‹ıË-ÛË, Ì ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· Ô˘ ÂȉÚÔ‡ÓÛÙÔ Ì˘ÔοډÈÔ. ¶ÈÛÙ‡ÂÙ·È fiÙÈ Ë ‰Ú¿ÛË Ù˘ÙÔ͛Ӣ ÛÙ· ·ÙÙ·Ú· Î·È Ë ‰Ú¿ÛË ÙÔ˘ TNF ÛÙԉȷÊÔÚÈÎfi ‰˘Ó·ÌÈÎfi Ù˘ ΢ÙÙ·ÚÈ΋˜ ÌÂÌ‚Ú¿-Ó˘, Â›Ó·È ˘Â‡ı˘Ó˜ ÁÈ· ÙȘ ·Ú·¿Óˆ ‰È·Ù·-Ú·¯¤˜.

˙. ∏ ˘ÔʈÛÊÔÚ·ÈÌ›· Î·È Ë ˘·Û‚ÂÛÙÈ·ÈÌ›· ·Ô-ÙÂÏÔ‡Ó ‰‡Ô ·Ú¿ÍÂÓ˜ ÂΉËÏÒÛÂȘ ÙÔ˘ TSS.∆Ô ¯·ÌËÏfi Ca ÔÊ›ÏÂÙ·È ÂÓ Ì¤ÚÂÈ ÛÙËÓ ˘Ô-ÚˆÙÂ˚Ó·ÈÌ›·, ·ÏÏ¿ Ê·›ÓÂÙ·È fiÙÈ Û˘Ó‰¤ÂÙ·È Î·ÈÌ ٷ ˘„ËÏ¿ ›‰· ÌÔÚÊ‹˜ ηÏÛÈÙÔÓ›Ó˘, ËÔÔ›· ¤¯ÂÈ ÌÂÙÚËı› ÛÙÔ TSS Î·È ¤¯ÂÈ ‰È·ÊÔ-ÚÂÙÈÎfi ÌÔÚÈ·Îfi ‚¿ÚÔ˜ ·fi ÙË Ê˘ÛÈÔÏÔÁÈ΋.

4. ÂΉËÏÒÛÂȘ ·fi ÙÔ ‰¤ÚÌ· Î·È ÙÔ˘˜ ‚ÏÂÓÓÔÁfi-ÓÔ˘˜ (¶›Ó·Î·˜ 1).

∫ÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ·fiÙÔ-

ÌË ¿ÓÔ‰Ô Ù˘ ıÂÚÌÔÎÚ·Û›·˜, ηÎÔ˘¯›·, Ì˘·ÏÁ›·,Î˘Ó¿Á¯Ë, Â̤ÙÔ˘˜ Î·È ˙¿ÏË. ™Â 24-48 ÒÚ˜ ·ÚÔ˘-ÛÈ¿˙ÔÓÙ·È ÂÎÎÚÈÙÈ΋ ‰È¿ÚÚÔÈ· (·ÔÙ¤ÏÂÛÌ· Ù˘ÂÓÙÂÚÔÙÔÍÈ΋˜ ‰Ú¿Û˘ Ù˘ TSS-1), ‰È¿¯˘ÙË ÂÚ˘-ıÚÔ‰ÂÚÌ›· Î·È ÂÁÎÂÊ·ÏÔ¿ıÂÈ· (ÔÊ›ÏÂÙ·È ÛÙԉȿ¯˘ÙÔ ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ·).

™ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË, ÂÎÙfi˜ ·fi ÙÔÓ ˘ÚÂÙfi,‰È·ÈÛÙÒÓÔÓÙ·È Ù·¯˘Î·Ú‰›·, Ù·¯‡ÓÔÈ·, ˘fiÙ·ÛË,Ô›‰ËÌ·, ÂÈÂÊ˘Î›Ùȉ·, ÂÚ˘ıÚfiÙËÙ· ‚ÏÂÓÓÔÁfiÓˆÓ,˘ÓËÏ›·, ¢ÂÚÂıÈÛÙfiÙËÙ·. ™Â ÔÛÔÛÙfi ÌÂÁ·Ï‡ÙÂÚÔÙÔ˘ 30% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ·Ô˘ÛÈ¿˙ÂÈ Î¿ÔÈÔ˜ ·-Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘.

™Â οı ·È‰› Ô˘ Í·ÊÓÈο ·ÚÔ˘ÛÈ¿˙ÂÈ ˘ÚÂÙfi,ÂÍ¿ÓıËÌ· ‹ ˘fiÙ·ÛË, ÙÔ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎfi TSS ı·Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿-ÁÓˆÛË.

∂ÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜O ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÂÚÈÏ·Ì‚¿ÓÂÈ ÌÂÁ¿-

ÏË ÛÙÚÔÊ‹ ÙÔ˘ Ù‡Ô˘ ÙˆÓ ÔÏ˘ÌÔÚÊÔ‡ÚËÓˆÓÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿ Ì ‹ ¯ˆÚ›˜ Ï¢ÎÔ΢ÙÙ¿ÚˆÛË,ıÚÔÌ‚Ô΢ÙÔÂÓ›·, ‰È¿¯˘ÙË ÂÓ‰·ÁÁÂȷ΋ ‹ÍË,˘·Û‚ÂÛÙÈ·ÈÌ›· Î·È ˘ÔʈÛÊÔÚ·ÈÌ›·.

∏ ÁÂÓÈÎÂ˘Ì¤ÓË Ì˘·ÏÁ›· Î·È Ë Ì˘˚΋ ·‰˘Ó·Ì›·Û˘Óԉ‡ÔÓÙ·È ·fi ·˘ÍË̤ӷ ›‰· ÎÚ·ÙÈÓÈ΋˜ÊˆÛÊ·Ù¿Û˘ (CPK) ÛÙÔÓ ÔÚfi (Èı·Ófiٷٷ ˆ˜ ·Ô-Ù¤ÏÂÛÌ· Ù˘ ‰Ú¿Û˘ ÙˆÓ IL-1 Î·È TNF Ô˘ ÚÔη-ÏÔ‡Ó ÚˆÙÂfiÏ˘ÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÚÔÛÙ·-ÁÏ·Ó‰›Ó˘ ∂2, Ô˘ Â›Ó·È ÈÛ¯˘Úfi˜ ‰ÈÂÁ¤ÚÙ˘ ÙˆÓ Â-ÚÈÊÂÚÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ fiÓÔ˘).

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·99

Staphylococcus aureus ÌÔÚ› Ó· ·ÔÌÔÓˆı›·fi ÙËÓ ÂÛÙ›· Ïԛ̈͢ Û ÔÛÔÛÙfi >85% ÙˆÓ Â-ÚÈÙÒÛˆÓ.

∆· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ TSST-1 ηٿ ÙËÓÔÍ›· Ê¿ÛË ·Ô˘ÛÈ¿˙Ô˘Ó, ÂÓÒ Î·Ù¿ ÙËÓ ·Ó¿ÚÚˆÛˢ¿Ú¯ÂÈ ˘„ËÏfi˜ Ù›ÙÏÔ˜ ·ÓÙÈۈ̿وÓ. OÈ ·ÈÌÔηÏ-ÏȤÚÁÂȘ ·Ú·Ì¤ÓÔ˘Ó ÛÙ›Ú˜ ηٿ ÙËÓ ÔÍ›· Ê¿-ÛË (7).

¢È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÙÔ˘ staph-TSS∏ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ‰ÂÓ ÂÍ·ÚÙ¿Ù·È Ô‡-

Ù ÂȂ‚·ÈÒÓÂÙ·È ·fi ÙËÓ ·ÔÌfiÓˆÛË ÌÈÎÚÔ‚›Ô˘,ÙËÓ ·Ó›¯Ó¢ÛË Â͈ÙÔÍÈÓÒÓ ‹ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈÂ͈ÙÔÍÈÓÒÓ, ·ÏÏ¿ Ù›ıÂÙ·È ·ÔÎÏÂÈÛÙÈο Ì ÎÏÈÓÈοÎÚÈÙ‹ÚÈ· (8). ∞˘Ù¿ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó:

·) ˘ÚÂÙfi >38,9ÔC, ‚) ÂÍ¿ÓıËÌ· ‰È¿¯˘ÙÔ ÎËÏȉ҉˜, Á) ·ÔϤÈÛË ·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ 1-2 ‚‰ÔÌ¿-

‰Â˜ ÌÂÙ¿ ÙËÓ ÂΉ‹ÏˆÛË Ù˘ ÓfiÛÔ˘, ‰) ˘fiÙ·ÛË (ηıÔÚÈ˙fiÌÂÓË Û·Ó Û˘ÛÙÔÏÈ΋ <90

mmHg ÁÈ· ÙÔ˘˜ ÂÓ‹ÏÈΘ Î·È <5Ë ∂.£. ÁÈ· Ù· ·È‰È¿ËÏÈΛ·˜ <16 ÂÙÒÓ, ÙÒÛË Ù˘ ‰È·ÛÙÔÏÈ΋˜ ·ÚÙËÚÈ·-΋˜ ›ÂÛ˘ >15 mmHg ηٿ ÙË ÌÂÙ¿‚·ÛË ·fi ÙËÓηٷÎÂÎÏÈ̤ÓË ÛÙËÓ fiÚıÈ· ı¤ÛË, ÔÚıÔÛÙ·ÙÈÎfi Û˘ÁÎÔ-ÈÎfi ÂÂÈÛfi‰ÈÔ ‹ ˙¿ÏË ÛÙËÓ fiÚıÈ· ı¤ÛË),

Â) ÚÔÛ‚ÔÏ‹ ÙÚÈÒÓ ‹ ÂÚÈÛÛfiÙÂÚˆÓ ·fi Ù··ÎfiÏÔ˘ı· ÔÚÁ·ÓÈο Û˘ÛÙ‹Ì·Ù·: Á·ÛÙÚÂÓÙÂÚÈÎÔ‡(¤ÌÂÙÔÈ ‹ ‰È·ÚÚÔ˚Τ˜ ÎÂÓÒÛÂȘ ÛÙËÓ ¤Ó·ÚÍË Ù˘ Ófi-ÛÔ˘), Ì˘˚ÎÔ‡ (ÛËÌ·ÓÙÈ΋ Ì˘·ÏÁ›· ‹ CPK ÔÚÔ‡>2Ï¿ÛÈÔ Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ÙÈÌ‹˜), ‚ÏÂÓÓÔÁfiÓˆÓ(˘ÂÚ·ÈÌ›· ÂÈÂÊ˘ÎfiÙˆÓ, ÛÙÔÌ·ÙÔÊ¿Ú˘ÁÁ·, ÎfiÏ-Ô˘), Ô˘ÚÔÔÈËÙÈÎÔ‡ (Ô˘Ú›· ‹ ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡>2Ï¿ÛÈÔ Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ÙÈÌ‹˜ ‹ ˘ÔÛÊ·›ÚÈ·>5 ÎÔ Â› ·Ô˘Û›·˜ Ô˘ÚÔÏԛ̈͢), ‹·ÙÔ˜ (ÔÏÈ-΋ ¯ÔÏÂÚ˘ıÚ›ÓË, SGOT ‹ SGPT >2Ï¿ÛÈÔ Ù˘ Ê˘-ÛÈÔÏÔÁÈ΋˜ ÙÈÌ‹˜), ·ÈÌÔÔÈËÙÈÎÔ‡ (·ÈÌÔÂÙ¿ÏÈ·<100.000/mm3) Î·È ∫¡™ (‰È·Ù·Ú·¯¤˜ ÚÔÛ·Ó·ÙÔ-ÏÈÛÌÔ‡ ‹ ÙÔ˘ ÂȤ‰Ô˘ Û˘Ó›‰ËÛ˘, ¯ˆÚ›˜ ÂÛÙȷοÓ¢ÚÔÏÔÁÈο ÛËÌ›·, › ·Ô˘Û›·˜ ˘ÚÂÙÔ‡ Î·È˘fiÙ·Û˘).

ÛÙ) ·ÚÓËÙÈο ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ·ÎfiÏÔ˘ıˆÓ ÂÚ-

Á·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛˆÓ, Â¿Ó ÏËÊıÔ‡Ó: i) ηÏÏȤÚ-ÁÂȘ ·›Ì·ÙÔ˜ - Ê¿Ú˘ÁÁ· - ∂¡À (Ë Î·ÏÏȤÚÁÂÈ· ·›-Ì·ÙÔ˜ ÌÔÚ› Ó· Â›Ó·È ıÂÙÈ΋ ÁÈ· ¯Ú˘Û›˙ÔÓÙ· ÛÙ·-Ê˘ÏfiÎÔÎÎÔ) Î·È ii) ÔÚÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· ÎËÏȉÒ-‰Ë ˘ÚÂÙfi ÙˆÓ ‚Ú·¯ˆ‰ÒÓ ÔÚ¤ˆÓ, ÏÂÙÔÛ›ڈÛË‹ ÈÏ·Ú¿.

¶Èı·Ó‹ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È fiÙ·Ó ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È5 ·fi Ù· 6 ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ·, ÂÓÒ Ë ‰È¿ÁÓˆÛËÙ›ıÂÙ·È Ì ‚‚·ÈfiÙËÙ· fiÙ·Ó ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Î·È Ù·6 ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ·, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤Ó˘Ù˘ ·ÔϤÈÛ˘ (ÂÎÙfi˜ Â¿Ó Ô ·ÛıÂÓ‹˜ ηٷϋÍÂÈÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ·ÔϤÈÛ˘).

£Âڷ›· ∏ ıÂڷ›· ÙÔ˘ staph-TSS ‚·Û›˙ÂÙ·È Û ÙÚÂȘ

‚·ÛÈΤ˜ ·Ú¯¤˜: ·) ÛÙË Ì˯·ÓÈ΋ ·Ê·›ÚÂÛË Ù˘ ÙÔ͛Ӣ Ô˘ ·-

Ú¿ÁÂÈ o S. aureus, Ì ·ÚÔ¯¤Ù¢ÛË Î·È Ù·˘ÙÔÔ›Ë-ÛË ·fi ÙË ı¤ÛË Ù˘ ·Ú·ÁˆÁ‹˜ Ù˘ ÙÔ͛Ӣ (.¯.Û staph-TSS ·fi ¤ÌÌËÓÔ Ú‡ÛË, ·Ê·›ÚÂÛË ÙÔ˘tampon). OÈ ÏÔÈÌÒÍÂȘ ÙˆÓ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ Î·È ÔȯÂÈÚÔ˘ÚÁÈΤ˜ ÏÔÈÌÒÍÂȘ ı· Ú¤ÂÈ Ó· ·ÚÔ¯ÂÙ‡Ô-ÓÙ·È Î·È Ó· ·Ê·ÈÚÂ›Ù·È ÙÔ Í¤ÓÔ ˘ÏÈÎfi.

‚) ÛÙËÓ ·ÓÙÈÌÈÎÚԂȷ΋ ıÂڷ›·, ÁÈ· Ó· ÛÙ·Ì·-Ù‹ÛÂÈ Ë ·Ú·ÁˆÁ‹ Ù˘ ÙÔ͛Ӣ Î·È Ó· ÂÍÔ˘‰ÂÙÂÚˆ-ı› Ô ÌÈÎÚÔÔÚÁ·ÓÈÛÌfi˜. À„ËϤ˜ ‰fiÛÂȘ IV ·ÓÙÈÛÙ·-Ê˘ÏÔÎÔÎÎÈ΋˜ ‚-Ï·ÎÙ¿Ì˘ (ÔÍ·ÎÈÏÏ›ÓË, ÊÏÔ˘ÎÏÔÍ·-ÎÈÏÏ›ÓË, ÎÂÊ·˙ÔÏ›ÓË) ‹ ‚·ÓÎÔÌ˘Î›Ó˘ Ú¤ÂÈ Ó· ¯Ô-ÚËÁËıÔ‡Ó ÙÔ Û˘ÓÙÔÌfiÙÂÚÔ ‰˘Ó·Ùfi. ¶Ú¤ÂÈ Ó· ¯Ô-ÚËÁÔ‡ÓÙ·È ˘„ËϤ˜ ‰fiÛÂȘ Ê·Ú̿ΈÓ, ‰ÈfiÙÈ ÔÈ ¯·ÌË-Ϥ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ¤¯Ô˘Ó ‰Â›ÍÂÈ in vitro fiÙÈ ·Ó‚¿-˙Ô˘Ó ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ TSST-1 (9).

™˘ÓÈÛÙ¿Ù·È Ë ¯ÔÚ‹ÁËÛË IV ÎÏÈÓ‰·Ì˘Î›Ó˘, ‰ÈfiÙÈË ÎÏÈÓ‰·Ì˘Î›ÓË Î·È ÔÈ ¿ÏϘ Ì·ÎÚÔÏ›‰Â˜ ·Ó·ÛÙ¤Ï-ÏÔ˘Ó ÙË ‚·ÎÙËÚȉȷ΋ ÚˆÙÂ˚ÓÈ΋ Û‡ÓıÂÛË Î·È ¤¯ÂÈ·Ô‰Âȯı› fiÙÈ Î·Ù·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ·Ú·ÁˆÁ‹ Ù˘TSST-1 in vitro, Û ̛· Û˘ÁΤÓÙÚˆÛË ¯·ÌËÏfiÙÂÚËÙÔ˘ 1/64 Ù˘ ÌÈÎÚfiÙÂÚ˘ ·Ó·ÛÙ·ÏÙÈ΋˜ Û˘ÁΤÓÙÚˆ-Û˘ (10).

Á) ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ Û˘ÛÙËÌ·ÙÈÎÒÓ ÂΉË-ÏÒÛÂˆÓ ·fi ÙËÓ ÙÔÍ›ÓË ‹ ÙÔ˘˜ ÌÂÙ·‚È‚·ÛÙ¤˜. ™Â

¶·È‰È·ÙÚÈ΋ 2003;66:97-103 Paediatriki 2003;66:97-103

100

¶›Ó·Î·˜ 1. ¢ÂÚÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ ÙÔ˘ TSS

∂Ή‹ÏˆÛË ÃÚfiÓÔ˜ ÂÌÊ¿ÓÈÛ˘

ñ °ÂÓÈÎÂ˘Ì¤ÓË ÎËÏȉ҉˘ ÂÚ˘ıÚÔ‰ÂÚÌ›· ¶ÚÒÈÌË (Û˘¯Ó¿ ·ÚÔ‰È΋)ñ ∂ί˘ÌÒÛÂȘ (·Û˘Ó‹ı˘) ¶ÚÒÈÌËñ ∂Ú˘ıÚfiÙ˘ ·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ ¶ÚÒÈÌËñ °ÂÓÈÎÂ˘Ì¤ÓÔ Ô›‰ËÌ· ¶ÚÒÈÌËñ ºÏ‡ÎÙ·ÈÓ˜-Ê˘Û·Ï›‰Â˜ (·Û˘Ó‹ı˘) ¶ÚÒÈÌËñ ∫ÓȉˆÙÈÎfi ÎËÏȉԂϷÙȉ҉˜ ÂÍ¿ÓıËÌ· 7-14 Ë̤Ú˜ñ ∞ÔϤÈÛË ‰·ÎهψÓ-·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ 10-21 Ë̤Ú˜ñ ∞ÒÏÂÈ· Ì·ÏÏÈÒÓ-ÔÓ‡¯ˆÓ 4-12 ‚‰ÔÌ¿‰Â˜

ñ ŒÓÙÔÓÔ ÂÚ‡ıËÌ· ÂÈÂÊ˘ÎfiÙˆÓ Î·È ‚ÏÂÓÓÔÁfiÓˆÓ (ÛÙfiÌ·ÙÔ˜, ÁÏÒÛÛ·˜, Ê¿Ú˘ÁÁ·-ÎfiÏÔ˘, Ù˘Ì·ÓÈ΋˜ ÌÂÌ‚Ú¿Ó˘)ñ ªÔÚÔÂȉ‹˜ ÁÏÒÛÛ·ñ ∞ÈÌÔÚÚ·Á›Â˜ ˘fi ÙÔÓ ÂÈÂÊ˘ÎfiÙ·ñ ∂ÍÂÏÎÒÛÂȘ ÛÙfiÌ·ÙÔ˜-ÎfiÏÔ˘-ÔÈÛÔÊ¿ÁÔ˘-·ÛÙˆ˜

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·100

¶·È‰È·ÙÚÈ΋ 2003;66:97-103 Paediatriki 2003;66:97-103

101

ÂÈÚ·Ì·Ùfi˙ˆ·, ÙÔ staph-TSS ÌÔÚ› Ó· ÚÔÏËÊı›Ì ÙË ¯ÔÚ‹ÁËÛË ·ÓıÚÒÈÓ˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘,fiÙ·Ó ¯ÔÚËÁËı› ÂÓ‰ÔÊÏ‚›ˆ˜ ÂÓÙfi˜ 30 ˆÚÒÓ ·fiÙË ‰Ú¿ÛË Ù˘ TSST-1. ∏ IVIG ÂÚȤ¯ÂÈ ˘„ËϤ˜ Û˘-ÁÎÂÓÙÚÒÛÂȘ ·Ó·ÛÙ·ÏÙÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÂÓ·ÓÙ›ÔÓÙ˘ TSST-1 Î·È ¿ÏÏˆÓ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎÒÓ ÂÓÙÂÚÔÙÔ-ÍÈÓÒÓ (11). ŸÌˆ˜, ÛÙ· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· Ô˘¤¯ÂÈ ¯ÚËÛÈÌÔÔÈËı›, ¤¯ÂÈ ·Ú·ÙËÚËı› Âȉ›ӈÛËÙˆÓ ·ÛıÂÓÒÓ ÌÂÙ¿ ·fi ÌÂÚÈΤ˜ ÒÚ˜ Î·È ‰ÂÓ Û˘ÓÈ-ÛٿٷÈ.

∑ˆÙÈ΋˜ ÛËÌ·Û›·˜ Â›Ó·È Ë ·ÔηٿÛÙ·ÛË ÙÔ˘ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘ Î·È Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘,Ì ÙË ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ (ÎÚ˘ÛÙ·ÏÏÔÂȉ‹, ÎÔÏÏÔÂÈ-‰‹) Î·È ÈÓÔÙÚfiˆÓ (ÓÙÔ·Ì›ÓË-ÓÙÔÌÔ˘Ù·Ì›ÓË). ™Â·ÚÎÂÙ¤˜ ÂÚÈÙÒÛÂȘ, Â›Ó·È ·Ó·Áη›Ô˜ Ô Ì˯·ÓÈÎfi˜·ÂÚÈÛÌfi˜.

™ÙÚÂÙÔÎÔÎÎÈÎfi TSS∂ȉËÌÈÔÏÔÁ›· ¶ÂÚÈÁÚ¿ÊËΠÙÔ 1989, ÌÂÙ¿ ·fi ÛÔ‚·Ú¤˜ ÏÔÈ-

ÌÒÍÂȘ ·fi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ ∞. ∂ΉËÏÒ-ÓÂÙ·È Û fiϘ ÙȘ ËÏÈ˘, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤ӈÓÎ·È ÙˆÓ ·È‰ÈÒÓ. ™ÙÔÓ ∫·Ó·‰¿, Ô ÂÙ‹ÛÈÔ˜ ‰Â›ÎÙ˘ÙÔ˘ strep-TSS ÛÙ· ·È‰È¿ Â›Ó·È 0,08 ÂÚÈÙÒÛÂȘ·Ó¿ 100.000 (12). ∞Ú¯Èο, Ë ·ÓÂÌÔ‚ÏÔÁÈ¿ ıˆڋ-ıËΠˆ˜ Ô ÌÂÁ·Ï‡ÙÂÚÔ˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ·ÙËÓ ·Ó¿Ù˘ÍË strep-TSS. OÈ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈ-ÙÒÛÂȘ Â›Ó·È ÛÔÚ·‰ÈΤ˜.

¶·ıÔÁ¤ÓÂÈ·£ÂˆÚÂ›Ù·È fiÙÈ Â›Ó·È ›‰È· Ì ÂΛÓË ÙÔ˘ staph-

TSS. ¶·Ú’ fiÏ· ·˘Ù¿, ˘¿Ú¯Ô˘Ó Ô˘ÛÈÒ‰ÂȘ ‰È·ÊÔ-Ú¤˜ ÙfiÛÔ ÛÙËÓ ·ıÔÁ¤ÓÂÛË, fiÛÔ Î·È ÛÙȘ ÎÏÈÓÈΤ˜ÂΉËÏÒÛÂȘ (¶›Ó·Î·˜ 2).

¶¤ÓÙ ÙÔ˘Ï¿¯ÈÛÙÔÓ ‰È·ÊÔÚÂÙÈΤ˜ ÛÙÚÂÙÔÎÔÎÎÈ-Τ˜ Â͈ÙÔ͛Ә ‰ÚÔ˘Ó Û·Ó ˘ÂÚ·ÓÙÈÁfiÓ· in vitro.∞ÏÏ¿ in vivo, Ô ÚfiÏÔ˜ ÙÔ˘˜ Â›Ó·È ÏÈÁfiÙÂÚÔ Î·Ï¿·ÓÙÈÏËÙfi˜, ·ÊÂÓfi˜ ‰ÈfiÙÈ Ë ·ÚÔ˘Û›· ÙÔ˘˜ ‰ÂÓ Â›-

Ó·È ÛÙÂÓ¿ Û˘Ó‰Â‰Â̤ÓË Ì ÙÔ strep-TSS, ·ÊÂÙ¤ÚÔ˘ÁÈ·Ù› Ë ÂÏ¿ÙÙˆÛË ÙˆÓ ÎÏÒÓˆÓ V‚ Ô˘ ·Ú·ÙËÚ›ٷÈÛ ·ÛıÂÓ›˜ Ì strep-TSS, ‰ÂÓ Â›Ó·È ÂȉÈ΋ ÁÈ· η-Ì›· ·fi ·˘Ù¤˜ ÙȘ ÙÔ͛Ә (13). ∂›Û˘, ¿ÏÏÔÈ ·-Ú¿ÁÔÓÙ˜ ÓÔÛËÚfiÙËÙ·˜, fiˆ˜ ÔÈ ·ÓÙÈÊ·ÁÔ΢ÙÙ·ÚÈ-Τ˜ ÚˆÙ½Ó˜ ª ÂÈÊ·Ó›·˜ Î·È ÙÔ ÏÈÔÙ¯ÓÔ˚ÎfiÔ͇ (Ô˘ ¢ԉÒÓÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ÙÔ˘ TNF-a), ÌÔ-Ú› Ó· Û˘Ì‚¿ÏÔ˘Ó ·Â˘ı›·˜ ÛÙËÓ ÂΉ‹ÏˆÛË ÙÔ˘strep-TSS. ∞fi ÙËÓ ¿ÏÏË ÌÂÚÈ¿, ·Ó·ÊÔÚ¤˜ ·fi ¢-ÂÚÁÂÙÈο ·ÔÙÂϤÛÌ·Ù· Ù˘ ¯ÔÚ‹ÁËÛ˘ IVIG ÛÙÔstrep-TSS, ηıÒ˜ Î·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë IVIG ÂÚȤ-¯ÂÈ ·ÓÙÈÛÒÌ·Ù· Ô˘ ÂÍÔ˘‰ÂÙÂÚÒÓÔ˘Ó ·ÚÎÂÙÔ‡˜ÛÙÚÂÙÔÎÔÎÎÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÓÔÛËÚfiÙËÙ·˜, ÂÓÈ-Û¯‡Ô˘Ó ÙËÓ ¿Ô„Ë ÁÈ· ÙÔ ÚfiÏÔ ÙˆÓ ÛÙÚÂÙÔÎÔÎÎÈ-ÎÒÓ Â͈ÙÔÍÈÓÒÓ ÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙÔ˘ strep-TSS.™Â ·ÓÙ›ıÂÛË Ì ÙÔ staph-TSS, ÙÔ strep-TSS Û˘ÓÔ-‰Â‡ÂÙ·È Û˘Ó‹ıˆ˜ ·fi ÛÔ‚·Ú‹ ÙÔÈ΋ Ïԛ̈ÍË ·fiÛÙÚÂÙfiÎÔÎÎÔ ÔÌ¿‰·˜ ∞, Û˘¯Ó¿ Û˘Óԉ¢fiÌÂÓË·fi ‚·ÎÙËÚÈ·ÈÌ›·.

∫ÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ∏ ‡ÏË ÂÈÛfi‰Ô˘ ÙÔ˘ ÛÙÚÂÙfiÎÔÎÎÔ˘ ÔÌ¿‰·˜ ∞

·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙË ÛÙÔ 50% ÙˆÓ ÂÚÈÙÒÛˆÓ(12). ∞fi ÙËÓ ¿ÏÏË, ηٷÛÙ¿ÛÂȘ fiˆ˜ ¯ÂÈÚÔ˘ÚÁÈ-Τ˜ ÂÂÌ‚¿ÛÂȘ, ÙÔÎÂÙfi˜, ÏÔÈÌÒÍÂȘ ‰¤ÚÌ·ÙÔ˜(·ÓÂÌÔ‚ÏÔÁÈ¿) ‹ ÌÈÎÚfi ‰ÂÚÌ·ÙÈÎfi ÙÚ·‡Ì· ÌÔÚÔ‡ÓÓ· ˘¿ÚÍÔ˘Ó ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË strep-TSS.

∂Ï·ÊÚ¿ ÚÔ‰ÚÔÌÈο Û˘ÌÙÒÌ·Ù· ‰È¿ÚÎÂÈ·˜ 1-3 ËÌÂÚÒÓ ÌÔÚ› Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó ÚÈÓ ÙËÓ ÂΉ‹Ïˆ-ÛË ˘„ËÏÔ‡ ˘ÚÂÙÔ‡. ¶ÔÛÔÛÙfi 80% ÂÚ›Ô˘ ÙˆÓÂÚÈÙÒÛˆÓ, ·ÚÔ˘ÛÈ¿˙ÂÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ·fi ÏÔÈÌÒÍÂȘ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ (΢ÙÙ·Ú›ÙȘ, ¯ÂÈ-ÚÔ˘ÚÁÈΤ˜ ÏÔÈÌÒÍÂȘ, Ì˘ÔÛ›ÙȘ, ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔ-Ó›ÙȘ).

∆Ô shock Î·È Ë ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· ›ӷȷÔÙ¤ÏÂÛÌ· ‰‡Ô ·Ú·ÁfiÓÙˆÓ (6): ·) Ù˘ ·Â˘ı›-·˜ ‰Ú¿Û˘ Ù˘ ÙÔ͛Ӣ Î·È ÙˆÓ ÌÂÙ·‚È‚·ÛÙÒÓ Ûٷ·ÙÙ·Ú· Î·È Ù˘ ÈÛÙÈ΋˜ ÈÛ¯·ÈÌ›·˜, Ô˘ ·Ú¯Èο

¶›Ó·Î·˜ 2. ™˘ÁÎÚÈÙÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ÙÔÍÈÎÒÓ shock Û˘Ó‰ÚfïÓ

Strep TSS Staph TSS

∆Ô͛Ә speA, speB, speC ÛÙÚÂÙÔÎÔÎÎÈο ˘ÂÚ·ÓÙÈÁfiÓ· TSST-1, ÂÓÙÂÚÔÙÔ͛Ә∞ÓÔÛÔÏÔÁ›· ∂Ï¿ÙÙˆÛË ÎÏÒÓÔ˘ V‚ ∞‡ÍËÛË ÎÏÒÓÔ˘ V‚¶Úfi‰ÚÔÌ· Û˘ÌÙÒÌ·Ù· °Ú›Ë˜-like ŒÌÂÙÔ˜-‰È¿ÚÚÔÈ·¢È¿ÚÎÂÈ· Úfi‰ÚÔÌˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ∞fi ÒÚ˜ ̤¯ÚÈ Ë̤Ú˜ flÚ˜™Ô‚·ÚfiÙËÙ· Úfi‰ÚÔÌˆÓ Û˘ÌÙˆÌ¿ÙˆÓ + +++∆ÔÈ΋ Ïԛ̈ÍË +++ +

(.¯. Ó¢ÌÔÓ›·, Ïԛ̈ÍË ÔÛÙÒÓ, ΢ÙÙ·Ú›ÙȘ, ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›ÙȘ)

£ÂÙÈ΋ ·ÈÌÔηÏÏȤÚÁÂÈ· +++ -¶fiÓÔ˜ ÛÙËÓ ÂÓÙfiÈÛË Ù˘ Ïԛ̈͢ +++ +∂Í¿ÓıËÌ· OÛÙÚ·ÎÈ҉˜ ∂Ú˘ıÚÔ‰ÂÚÌ›·Shock ¢‡ÛÎÔÏÔ Ó· ·ÓÙÈÌÂÙˆÈÛÙ› ∞ÓÙÈÌÂÙˆ›˙ÂٷȶÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· +++ +¢È·Ù·Ú·¯¤˜ ‹Í˘ +++ +£ÓËÙfiÙËÙ· À„ËÏ‹ ÷ÌËÏ‹

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·101

ÔÊ›ÏÂÙ·È ÛÙËÓ ·ÒÏÂÈ· ÙÔ˘ ÙfiÓÔ˘ ÙˆÓ ·ÁÁ›ˆÓ ηȂ) ÛÙÔ ÂÎÙÂٷ̤ÓÔ ‰È¿ÌÂÛÔ Ô›‰ËÌ· Ô˘ Û˘ÌȤ˙ÂÈÎ·È ÚÔηÏ› ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÁÁ›ˆÓ.

∆Ș ÂfiÌÂÓ˜ 24-48 ÒÚ˜ ÌÔÚ› Ó· ·ÚÔ˘ÛÈ·-ÛÙÔ‡Ó ARDS (ÏfiÁˆ Ù˘ ÙÚȯÔÂȉÈ΋˜ ‰È·Ê˘Á‹˜ η-Ù¿ ÙË ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ·Ó·Ï‹ÚˆÛ˘), Ì˘ÔηÚ-‰ÈÔ¿ıÂÈ· ¢∂¶ Î·È ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (ÓÂÊÚÈÎ‹Î·È ÚÔÓÂÊÚÈ΋). ∏ ıÓËÙfiÙËÙ· ·Ó¤Ú¯ÂÙ·È Û ÔÛÔ-ÛÙfi 30-70%.

¢È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÁÈ· ÙÔ strep-TSS (8) 1. ∞ÔÌfiÓˆÛË ÛÙÚÂÙfiÎÔÎÎÔ˘ ÔÌ¿‰·˜ ∞:

·. ·fi Ê˘ÛÈÔÏÔÁÈο ÛÙ›ڷ ÂÛÙ›· (.¯. ·›Ì·, ÂÁÎÂ-Ê·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi, ÂÚÈÙÔÓ·˚Îfi ˘ÁÚfi, ‚ÈÔ„›·ÈÛÙÒÓ, ¯ÂÈÚÔ˘ÚÁÈÎfi ÙÚ·‡Ì·) Î·È ‚. ·fi Ì›· fi¯È ÛÙ›ڷ ÂÛÙ›· (.¯. Ê¿Ú˘ÁÁ·˜, ÂÈÊ·-ÓÂȷ΋ ‰ÂÚÌ·ÙÈ΋ ‚Ï¿‚Ë).

2. ∫ÏÈÓÈο ÛËÌ›· Ô˘ ‰Â›¯ÓÔ˘Ó ÙË ÛÔ‚·ÚfiÙËÙ·ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·ÔÙÂÏÔ‡Ó: ·. Ë ˘fiÙ·ÛË (Û˘ÛÙÔÏÈ΋ ›ÂÛË <90 mmHg ÛÙÔ˘˜ÂÓ‹ÏÈΘ ‹ <5Ë ÂηÙÔÛÙÈ·›· ı¤ÛË ÛÙ· ·È‰È¿) Î·È ‚. 2 ‹ ÂÚÈÛÛfiÙÂÚ· ·fi Ù· ·ÎfiÏÔ˘ı·:

i) ¡ÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·: ÎÚ·ÙÈÓ›ÓË >2 mg/dl (ÙÈ-̤˜ >2Ï¿ÛÈÔ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ)

ii) ¢È·Ù·Ú·¯¤˜ ‹Í˘: ∞ª¶ <100.000/mm3 ‹¢∂¶

iii) ◊·Ú: ·‡ÍËÛË SGOT, SGPT ‹ ÔÏÈ΋˜ ¯ÔÏÂ-Ú˘ıÚ›Ó˘ (ÙÈ̤˜ >2Ï¿ÛÈÔ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ)

iv) ARDS v) ∂Í¿ÓıËÌ· ÎËÏȉ҉˜, Ô˘ ÌÔÚ› Ó· ÂÍÂÏÈ-

¯ı› Û ·ÔϤÈÛË vi) ¡¤ÎÚˆÛË Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ, ÂÚÈÏ·Ì‚¿ÓÔ-

ÓÙ·˜ ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›Ùȉ· ‹ Ì˘ÔÛ›Ùȉ· ‹ Á¿Á-ÁÚ·ÈÓ·.

∏ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È Ì ‚‚·ÈfiÙËÙ· fiÙ·Ó ÂÚÈ-Ï·Ì‚¿ÓÔÓÙ·È Ù· ÎÚÈÙ‹ÚÈ· 1· Î·È 2 (· Î·È ‚), ÂÓÒ Ë‰È¿ÁÓˆÛË Â›Ó·È Èı·Ó‹ fiÙ·Ó ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ù·ÎÚÈÙ‹ÚÈ· 1‚ Î·È 2 (· Î·È ‚).

£Âڷ›· OÈ ·Ú¯¤˜ Ù˘ ·ÓÙÈÌÂÙÒÈÛ˘ ÙÔ˘ strep-TSS ›ӷÈ

›‰È˜ Ì ÂΛӘ ÙÔ˘ staph-TSS. ∏ Ì˯·ÓÈ΋ ·Ê·›ÚÂÛË ÌÔÏ˘Ṳ̂ÓÔ˘ ͤÓÔ˘ ÛÒÌ·-

ÙÔ˜ Î·È Ë ·ÚÔ¯¤Ù¢ÛË Ù˘ ÌÔÏ˘Ṳ̂Ó˘ ÂÚÈÔ¯‹˜¤¯Ô˘Ó Ôχ ÌÂÁ¿ÏË ÛËÌ·Û›·, ÏfiÁˆ Ù˘ ·ÚÔ˘Û›·˜˘„ËÏ‹˜ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ.

™˘ÓÈÛÙ¿Ù·È ·ÓÙÈÌÈÎÚԂȷ΋ ıÂڷ›· Ì ¯ÔÚ‹-ÁËÛË IV ‚-Ï·ÎÙ¿Ì˘ Î·È ÎÏÈÓ‰·Ì˘Î›Ó˘. ∆Ô ÛÎÂÙÈ-Îfi Ù˘ ¯Ú‹Û˘ Ù˘ ÎÏÈÓ‰·Ì˘Î›Ó˘ Â›Ó·È ÔÏ˘·Ú·-ÁÔÓÙÈÎfi Î·È ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿-Ù˘Í˘ ÙÔ˘ ÛÙÚÂÙfiÎÔÎÎÔ˘ Û ˘„ËÏ‹ ˘ÎÓfiÙËÙ·,ηıÒ˜ ÔÈ ‚-Ï·Îٿ̘ Â›Ó·È ÏÈÁfiÙÂÚÔ ·ÔÙÂÏÂÛÌ·ÙÈ-Τ˜ (14), ÙËÓ Î·Ù·ÛÙÔÏ‹ Ù˘ ·Ú·ÁˆÁ‹˜ Ù˘ ‚·-ÎÙËÚȉȷ΋˜ ÙÔ͛Ӣ Î·È ÙËÓ Â˘ÎÔÏ›· ‚·ÎÙËÚȉȷ΋˜Ê·ÁÔ΢ÙÙ¿ÚˆÛ˘ ·fi ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ Û‡ÓıÂÛ˘

Ù˘ ÚˆÙ½Ó˘ ª. ™˘ÓÈÛٿٷÈ, ›Û˘, ¯ÔÚ‹ÁËÛË IVIG ÂÓ‰ÔÊÏÂ-

‚›ˆ˜, Ë ÔÔ›· ‚ÂÏÙÈÒÓÂÈ ÙËÓ ¤Î‚·ÛË ÙÔ˘ strep-TSS (11).

¶ÚÔʇϷÍË∏ ÂÊ·ÚÌÔÁ‹ ·ÓÙÈÌÈÎÚԂȷ΋˜ ·ÁˆÁ‹˜ ÓˆÚ›˜, ÛÂ

¤ÓÙÔÓ· ÌÔÏ˘Ṳ̂Ó˜ ‰ÂÚÌ·ÙÈΤ˜ ‚Ï¿‚˜ ·fi ·ÓÂÌÔ-‚ÏÔÁÈ¿, ηıÒ˜ Î·È Ë Â˘ÂÚÁÂÙÈ΋ ·ÓÔÛÔÔ›ËÛË ÁÈ·ÙËÓ ·ÓÂÌÔ‚ÏÔÁÈ¿, ÌÔÚ› Ó· ÚÔÏ¿‚Ô˘Ó ÏÔÈÌÒÍÂȘ·fi ÛÙÚÂÙfiÎÔÎÎÔ ÔÌ¿‰·˜ ∞, ηıÒ˜ Î·È ÙÔ strep-TSS. ÿÛˆ˜, Û ÎÏÂÈÛÙfi ·ÎÏÔ, ı· ÌÔÚÔ‡Û ӷ‚ÔËı‹ÛÂÈ Ë ¯ËÌÂÈÔÚÔʇϷÍË, ¯ˆÚ›˜ ·ÎfiÌË Ó· Û˘-ÛÙ‹ÓÂÙ·È Â˘Ú‡Ù·Ù·.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Broome CV. Epidemiology of toxic shock syndrome in the

United States: overview. Rev Infect Dis 1989;11 (Suppl1):S14-S21.

2. Jacobson JA, Kasworm EM, Reiser RF, Bergdoll MS. Lowincidence of toxic shock syndrome in children withstaphylococcal infection. Am J Med Sci 1987;294:403-407.

3. Lee VT, Chang AH, Chow AW. Detection of staphylococcalenterotoxin B among toxic shock syndrome (TSS)- andnon-TSS-associated Staphylo-coccus aureus isolates. JInfect Dis 1992;166: 911-915.

4. Parsonnet J. Nonmenstrual toxic shock syndrome: newinsights into diagnosis, pathogenesis, and treatment. CurrClin Top Infect Dis 1996;16:1-20.

5. Chesney PJ, Davis JP. Toxic shock syndrome. In: FeiginRD, Cherry JD, editors. Textbook of Pediatric InfectiousDiseases. 4th ed. Philadelphia: Saunders; 1998. p. 830-852.

6. µ·ÛÈÏfiÔ˘ÏÔ˜ ∞. ™‡Ó‰ÚÔÌÔ ÙÔÍÈÎÔ‡ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎÔ‡shock ÛÙ· ·È‰È¿. (¶ÂÚ›ÏË„Ë). 5o ™ÂÌÈÓ¿ÚÈÔ ∂›ÁÔ˘Û·˜∂ÓÙ·ÙÈ΋˜ ¶·È‰È·ÙÚÈ΋˜. ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ “¶.& ∞. ∫˘ÚÈ·ÎÔ‡”; 1991 ™Â٤̂ÚÈÔ˜; ∞ı‹Ó·; 1991. ÛÂÏ. 2-6.

7. Bergdoll MS, Crass BA, Reiser RF, Robbins RN, Davis JP. Anew staphylococcal enterotoxin, enterotoxin F, associatedwith toxic shock syndrome Staphylococcus aureus isolates.Lancet 1981;1:1017-1021.

8. Spentzas T. Index of suspicion. Case 1. Toxic shocksyndrome. Pediatr Rev 1999;20:199-201.

9. Kernodle DS, McGraw PA, Barg NL, Menzies BE, VoladriRK, Harshman S. Growth of Staphylococcus aureus withnafcillin in vitro induces alpha-toxin production andincreases the lethal activity of sterile broth filtrates in amurine model. J Infect Dis 1995;172:410-419.

10. Schlievert PM, Kelly JA. Clindamycin-induced suppressionof toxic shock syndrome-associated exotoxin production. JInfect Dis 1984;149:471.

11. Kaul R, McGeer A, Norrby-Teglund A, Kotb M, Schwartz B,O’Rourke K et al. Intravenous immunoglobulin therapy forstreptococcal toxic shock syndrome - a comparativeobservational study. The Canadian Streptococcal StudyGroup. Clin Infect Dis 1999;28:800-807.

12. Laupland KB, Davies HD, Low DE, Schwartz B, Green K,McGeer A. Invasive group A streptococcal disease in

¶·È‰È·ÙÚÈ΋ 2003;66:97-103 Paediatriki 2003;66:97-103

102

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¶·È‰È·ÙÚÈ΋ 2003;66:97-103 Paediatriki 2003;66:97-103

103

children and association with varicella-zoster virus infection.Ontario Group A Streptococcal Study Group. Pediatrics2000;105:60.

13. Watanabe-Ohnishi R, Low DE, McGeer A, Stevens DL,Schlievert PM, Newton D et al. Selective depletion of V beta-bearing T cells in patients with severe invasive group Astreptococcal infections and streptococcal toxic shocksyndrome. Ontario Streptococcal Study Project. J Infect Dis1995;171:74-84.

14. Stevens DL, Yan S, Bryant AE. Penicillin-binding proteinexpression at different growth stages determines penicillinefficacy in vitro and in vivo: an explanation for the inÔculumeffect. J Infect Dis 1993;167:1401-1405.

15. Schlievert PM, Shands KN, Dan BB, Schmid GP, NishimuraRD. Identification and characterization of an exotoxin fromStaphylococcus aureus associated with toxic-shocksyndrome. J Infect Dis 1981;143:509-516.

16. Vergeront JM, Stolz SJ, Crass BA, Nelson DB, Davis JP,

Begdoll MS. Prevalence of serum antibody tostaphylococcal enterotoxin F among Wisconsin residents:implications for toxic shock syndrome. J Infect Dis1983;148:692-698.

17. Notermans S, van Leeuwen WJ, Dufrenne J, Tips PD.Serum antibodies to enterotoxins produced byStaphylococcus aureus with special reference toenterotoxin F and toxic shock syndrome. J Clin Microbiol1983;18:1055-1060.

HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 15-07-2002 HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 14-02-2003

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∞. µ·ÛÈÏfiÔ˘ÏÔ˜ ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ ¶·È‰ÈÒÓ ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·

™ÎÔfi˜ - ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: °È· ÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÚfiÏÔ˘ÙÔ˘ ª. pneumoniae Î·È ÙÔ˘ C. pneumoniae ÛÙËÓ ·ÓÙȉڷ-ÛÙÈ΋ ÓfiÛÔ ÙˆÓ ·ÂÚ·ÁˆÁÒÓ, ÂÍÂÙ¿ÛÙËÎ·Ó 71 ·È‰È¿ ËÏÈΛ·˜2-14 ÂÙÒÓ Ì ¤Ó· ÂÂÈÛfi‰ÈÔ Û˘ÚÈÁÌÔ‡ Î·È 80 ˘ÁÈ‹ ·È‰È¿·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜. ∂Ï‹ÊıËÛ·Ó ‰Â›ÁÌ·Ù· ÔÚÔ‡ ÁÈ· ÙÔÓÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÂȤ‰ˆÓ ÂȉÈÎÒÓ ·ÓÙÈۈ̿وÓ, ηıÒ˜Î·È ÚÈÓÔÊ·Ú˘ÁÁÈÎfi ¤ÎÎÚÈÌ· ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ‰ÂÛÔ͢ÚÈ‚Ô-ÓÔ˘ÎÏÂ˚ÎÔ‡ ÔͤԘ ÙÔ˘ M. pneumoniae Î·È ÙÔ˘ C.pneumoniae, ηٿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙˆÓ ·ÛıÂÓÒÓ Î·È 4-6 ‚‰Ô-Ì¿‰Â˜ ÌÂÙ¿. ŸÏ· Ù· ·È‰È¿ ÌÂ Û˘ÚÈÁÌfi ·ÓÙÈÌÂÙˆ›ÛÙËÎ·Ó ÌÂηıÔÚÈṲ̂ÓË ·ÁˆÁ‹, Ô˘ ÂÚÈÂÏ¿Ì‚·Ó ÂÈÛÓÂfiÌÂÓ· ÎÔÚÙÈ-ÎÔÛÙÂÚÔÂȉ‹ Î·È ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈο ÁÈ· 5-7 Ë̤Ú˜. ŸÙ·Ó,˘fi ÙËÓ ÎÚ›ÛË ÙÔ˘ ÂÊËÌÂÚ‡ÔÓÙÔ˜ È·ÙÚÔ‡, ÚÔÛÙ¤ıËηÓÙÈ‚ÈÔÙÈÎfi, ÂÈϤ¯ıËÎÂ Ë ÎÏ·ÚÈıÚÔÌ˘Î›ÓË 15 mg/kg ۈ̷ÙÈ-ÎÔ‡ ‚¿ÚÔ˘˜ ÁÈ· 10 Ë̤Ú˜.∞ÔÙÂϤÛÌ·Ù·: OÍ›˜ ·Ó·Ó¢ÛÙÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi M.pneumoniae Î·È C. pneumoniae ÂÓÙÔ›ÛÙËÎ·Ó Ôχ ÈÔ Û˘-¯Ó¿ Û ·È‰È¿ ÌÂ Û˘ÚÈÁÌfi, Û ۯ¤ÛË Ì ٷ ·È‰È¿ Ù˘ ÔÌ¿‰·˜ÙˆÓ Ì·ÚÙ‡ÚˆÓ. ™Â ·ÛıÂÓ›˜ Ì Ïԛ̈ÍË ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ÂÍ·ÈÙ›·˜ ÂÓfi˜ ·fi ÙÔ˘˜ ‰‡Ô ·˘ÙÔ‡˜ ·ıÔÁfiÓÔ˘˜ ÌÈÎÚÔÔÚÁ·-ÓÈÛÌÔ‡˜, ÙÔ ÈÛÙÔÚÈÎfi ·ÓÂÈÏËÌÌ¤ÓˆÓ ÂÂÈÛÔ‰›ˆÓ Û˘ÚÈÁÌÔ‡‹Ù·Ó ÛËÌ·ÓÙÈο Û˘¯ÓfiÙÂÚÔ, Û ۯ¤ÛË Ì ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ ·-ÚÔ˘Û›·˙·Ó η̛· ·fi ÙȘ ÏÔÈÌÒÍÂȘ ·˘Ù¤˜. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ·ÙÚ›ÌËÓ˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÌÂٷ͇ ÙˆÓ ·È‰ÈÒÓ Ô˘ ‰ÂÓ

¤Ï·‚·Ó ·ÓÙÈ‚›ˆÛË, ·˘Ù¿ Ì ÔÍ›· Ïԛ̈ÍË ·fi M.pneumoniae Î·È C. pneumoniae ·ÚÔ˘Û›·Û·Ó ÛËÌ·ÓÙÈο˘„ËÏfiÙÂÚË ˘ÔÙÚÔ‹ ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Û˘ÚÈÁÌÔ‡, Û ۯ¤ÛËÌ ·˘Ù¿ ¯ˆÚ›˜ Ïԛ̈ÍË ·fi Ù· ·Ú·¿Óˆ ·ıÔÁfiÓ·(p=0,03). ™˘ÌÂÚ¿ÛÌ·Ù·: ∆· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ÛËÌ·ÙÔ‰ÔÙÔ‡Ó Ì›·Î·Ù·Ê·Ó‹ Û¯¤ÛË ÌÂٷ͇ ÙÔ˘ M. pneumoniae Î·È ÙÔ˘ C.pneumoniae Î·È ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Û˘ÚÈÁÌÔ‡ Û ·È‰È¿, ΢ڛˆ˜fiÙ·Ó ·˘Ù¿ Â›Ó·È Â·ÓÂÈÏËÌ̤ӷ, ηıÒ˜ Î·È ÙËÓ Èı·Ó‹ ‚ÂÏ-Ù›ˆÛË Ù˘ ÔÚ›·˜ Ù˘ ·ÓÙȉڷÛÙÈ΋˜ ÓfiÛÔ˘ ÙˆÓ ·ÂÚ·ÁˆÁÒÓÛ ·È‰È¿ Ì ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ Ïԛ̈͢ ·fi M.pneumoniae ηÈ/‹ C. pneumoniae.

™Ô˘‰·ÈfiÙËÙ· ÙˆÓ ÔͤˆÓ ·Ó·Ó¢ÛÙÈÎÒÓ ÏÔÈÌÒÍÂˆÓ ·fi Mycoplasma pneumoniae Î·È Chlamydiapneumoniae Û ·È‰È¿ Ì ÂÎÓ¢ÛÙÈÎfi Û˘ÚÈÁÌfi1

¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›·

1Esposito S, Blasi F, Arosio C, Fioravanti L, Fagetti L,Droghetti R et al Importance of acute Mycoplasma pneumoniae andChlamydia pneumoniae infections in children withwheezing Eur Respir J 2000;16:1142-1146

ª·Ú›· ÷Ù˙˯·Ú·Ï¿ÌÔ˘˜

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∏ ¯Ú‹ÛË Ù˘ ÙÔÈÚ·Ì¿Ù˘ ÛÙË ıÂڷ›· ·ÓıÂÎÙÈÎÒÓ ÂÈÏË„ÈÒÓ ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ M. ∆˙Ô‡ÊË, M. ÷ڛÛË, I. ¶·ÛÈ¿˜, A. ™ÈÒÌÔ˘, A. ™È·ÌÔÔ‡ÏÔ˘ - ª·˘Ú›‰Ô˘, Z. ¶··‰ÔÔ‡ÏÔ˘ - ∫Ô˘ÏÔ˘Ì‹

The use of topiramate in the treatment of drug-resistant epilepsies in children and adolescents M. Tzoufi, M. Charisi, I. Pasias, A. Siomou, A. Siamopoulou - Mavridou, Z. Papadopoulou - Couloumbis

∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞ ORIGINAL ARTICLE

∆Ô̤·˜ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ πˆ·ÓÓ›ÓˆÓ

Department of Child Health, Pediatric Clinic, University Hospital of Ioannina

�¶ÂÚ›ÏË„Ë: ∏ ÙÔÈÚ·Ì¿ÙË Â›Ó·È ¤Ó· Ó¤Ô ·ÓÙÈÂÈ-ÏËÙÈÎfi Ê¿ÚÌ·ÎÔ (∞∂º) Ô˘ ¯ÔÚËÁÂ›Ù·È Û ÂÓ‹ÏÈ-Θ Î·È ·È‰È¿ ËÏÈΛ·˜ ≥2 ÂÙÒÓ, ˆ˜ Û˘ÌÏËڈ̷ÙÈ-΋ ıÂڷ›· ÛÙËÓ ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÛÙȷ΋ÂÈÏË„›·. º·›ÓÂÙ·È, fï˜, fiÙÈ ÌÔÚ› Ó· Â›Ó·È ¯Ú‹-ÛÈÌË Î·È Û ·È‰È¿ Ì ÔÏÏ·ÏÔ‡˜ Ù‡Ô˘˜ ÎÚ›ÛˆÓ,fiˆ˜ ÛÙÔ Û‡Ó‰ÚÔÌÔ Lennox-Gastaut ‹ Û ·È‰È¿Ì ÂÈÏË„›Â˜ ·ÓıÂÎÙÈΤ˜ Û ¿ÏÏ· ∞∂º. ™ÎÔfi˜ Ù˘·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‹Ù·Ó Ë ·ÍÈÔÏfiÁËÛË Ù˘ ·ÔÙÂ-ÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Î·È Ù˘ ·ÛÊ¿ÏÂÈ·˜ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘,ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋˜ ·ÁˆÁ‹˜, Û ·È‰È¿ Ì ·ÓıÂ-ÎÙÈΤ˜ ÂÈÏË„›Â˜. H ·Ó·‰ÚÔÌÈ΋ ·˘Ù‹ ÌÂϤÙË ·ÊÔ-ÚÔ‡Û 17 ·ÛıÂÓ›˜ (6 ÎÔÚ›ÙÛÈ· Î·È 11 ·ÁfiÚÈ·), ËÏÈ-Λ·˜ 4,5-19 ÂÙÒÓ (̤ÛË ËÏÈΛ·: 10,4 ¤ÙË), Ì ̷ÎÚfi-¯ÚÔÓË Î·È ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÈÏË„›· (̤ÛˉȿÚÎÂÈ· ÓfiÛÔ˘: 6,9 ¤ÙË). ªÂ ‚¿ÛË ÙËÓ Ù·ÍÈÓfiÌËÛËÙ˘ ¢ÈÂıÓÔ‡˜ ŒÓˆÛ˘ ηٿ Ù˘ ∂ÈÏË„›·˜, 6 ·ÛıÂ-Ó›˜ ÂÌÊ¿ÓÈ˙·Ó ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· (3 Û˘Ìو̷-ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹) Î·È 11 ÂÛÙȷ΋ (8 Û˘Ìو̷ÙÈ-΋, 4 ÎÚ˘ÙÔÁÂÓ‹). ∞fi ·˘ÙÔ‡˜, 8 ÂÌÊ¿ÓÈ˙·Ó Û‡Ó-ıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, 3 ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ (2 ̉¢ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË), 4 Û‡Ó‰ÚÔÌÔ Lennox-Gastaut (1 ·Ú¯Èο Ì ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜), 1 Ì˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ Î·È 1 ÁÂÓÈÎÂ˘Ì¤ÓÔ˘˜ ÙÔÓÈ-ÎÔÎÏÔÓÈÎÔ‡˜ Û·ÛÌÔ‡˜. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ÂÏ¿Ì‚·-Ó·Ó ·fi 1 ¤ˆ˜ 4 ¿ÏÏ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η. ∏ÙÔÈÚ·Ì¿ÙË ÚÔÛÙ¤ıËΠÛÙ· Ê¿Ú̷η Ô˘ ‹‰Ë¤·ÈÚÓ·Ó ÔÈ ·ÛıÂÓ›˜, Û ‰fiÛË ¤Ó·Ú͢ 1 mg/kg/24h Î·È ·˘Í‹ıËΠÛÙ·‰È·Î¿, ·Ó¿ÏÔÁ· Ì ÙËÓ ·ÓÙ·fi-ÎÚÈÛË ÙˆÓ ·ÛıÂÓÒÓ Û 3-10 mg/kg/24 h. ∏ ·Ú·ÎÔ-ÏÔ‡ıËÛË ÙˆÓ ·ÛıÂÓÒÓ ‰È‹ÚÎÂÛ 5-15 Ì‹Ó˜. ªÂÙ¿ÙÔ ‰È¿ÛÙËÌ· ·˘Ùfi, ÙËÓ ·ÁˆÁ‹ Û˘Ó¤¯È˙·Ó 13/17·ÛıÂÓ›˜, ÂÓÒ ‰È·ÎfiËΠ۠4 ·ÛıÂÓ›˜ (23,5%),ÏfiÁˆ ÌË ‚ÂÏÙ›ˆÛ˘ (3) ‹ Âȉ›ӈÛ˘ (1) Ù˘ Û˘-¯ÓfiÙËÙ·˜ ÙˆÓ ÎÚ›ÛˆÓ. ∂Ï¿ÙÙˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜

�Abstract: Topiramate is a novel anti-epilepticdrug (AED) that is used in adults and in childrenaged ≥2 years, as adjunctive treatment of focalepilepsy that is resistant to drugs. However, itseems that it may also be useful in children withmultiple types of epilepsy, such as Lennox-Gastautsyndrome or in children with epilepsies that areresistant to other anti-epileptic drugs. The aim of thepresent study was the evaluation of effectivenessand safety in the use of the drug, as adjunctivetreatment, in children with drug-resistant epilepsy.In this retrospective study included 17 patients (6girls and 11 boys), aged between 4.5-19 years(median: 10.4 years) with long-term and drug-resistant epilepsy (median disease duration: 6.9years). Based on the classification of InternationalLeague Against Epilepsy, 6 had generalizedepilepsy (3 symptomatic, 3 cryptogenic) and 11 hadfocal epilepsy (8 symptomatic, 4 cryptogenic). Ofthese, 8 had complex partial seizures, 3 had partialseizures (2 with secondary generalization), 4 hadLennox-Gastaut syndrome (1 suffered primarilyfrom infantile spasms), 1 suffered from myoclonicabsences and 1 from generalized tonic-clonicseizures. All patients received 1-3 AEDs.Topiramate was added to the treatment regimenthat the patients were already taking, at a startingdose of 1 mg/kg/24 h and was gradually increased- depending on the patient’s response - to 3.0-10mg/kg/24 h. In 11/17 patients (64.7%)demonstrated ≥50% decrease in seizure activityand 6/17 patients (35.2%) became seizure free.Effectiveness was observed in various types ofseizures and types of epilepsy especially in anytype and etiology focal epilepsy. Adverse effects

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ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi ≥50% ÂÌ-Ê¿ÓÈÛ·Ó 11/17 ·ÛıÂÓ›˜ (64,7%), ÂÓÒ 6 ·fi ·˘-ÙÔ‡˜ ··ÏÏ¿¯ÙËÎ·Ó Ï‹Úˆ˜ (35,2%). ∞ÔÙÂÏÂÛÌ·-ÙÈÎfiÙËÙ· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ·Ú·ÙËÚ‹ıËΠ۠ÔÈΛ-ÏÔ˘˜ Ù‡Ô˘˜ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Î·È Û˘Ó‰ÚfïÓ,ȉȷ›ÙÂÚ· ÛÙËÓ ÔÔÈ·Û‰‹ÔÙ ÌÔÚÊ‹˜ Î·È ·ÈÙÈÔÏÔ-Á›·˜ ÂÛÙȷ΋ ÂÈÏË„›·. ¶·ÚÂÓ¤ÚÁÂȘ ÂÌÊ¿ÓÈÛ·Ó10/17 ·ÛıÂÓ›˜ (58,8%): 4 ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ηȷÓÔÚÂÍ›·, 4 ÂÈıÂÙÈÎfiÙËÙ· Î·È 2 ˘ÓËÏ›· Î·È ‰˘-ÛÎÔϛ˜ Û˘ÁΤÓÙÚˆÛ˘. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÙÔÈ-Ú·Ì¿ÙË ·Ô‰Â›¯ıËΠ·ÚÎÂÙ¿ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ηȷÛÊ·Ï‹˜ ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋ ıÂڷ›· Û 11/17·È‰È¿ Î·È ÂÊ‹‚Ô˘˜, Ì ¤Ó· ÌÂÁ¿ÏÔ Â‡ÚÔ˜ ·ÓıÂÎÙÈ-ÎÒÓ ÂÈÏË„ÈÒÓ, ÙfiÛÔ ÎÚ˘ÙÔÁÂÓÒÓ fiÛÔ Î·È Û˘-Ìو̷ÙÈÎÒÓ. ¶·Ú·ÙËÚ‹ıËΠ·ÓÙ·fiÎÚÈÛË Û Ô-ÛÔÛÙfi ≥50% ÛÙÔ 64,7% ÙˆÓ ·È‰ÈÒÓ Ù˘ ÌÂϤÙ˘.∆Ô Ê¿ÚÌ·ÎÔ ‹Ù·Ó ÁÂÓÈο ηÏÒ˜ ·ÓÂÎÙfi Î·È ÔÈ ·-ÚÂÓ¤ÚÁÂȘ Ô˘ ·ÚÔ˘ÛÈ¿ÛÙËÎ·Ó ÛÙÔ 58,8% ‹Ù·Óˆ˜ › ÙÔ Ï›ÛÙÔÓ ‹È˜ Î·È ·ÚÔ‰ÈΤ˜. ∆¤ÛÛÂÚȘ·ÛıÂÓ›˜ (23,5%) ‰È¤ÎÔ„·Ó ÙËÓ ·ÁˆÁ‹.

§¤ÍÂȘ ÎÏÂȉȿ: ÙÔÈÚ·Ì¿ÙË, ·ÓıÂÎÙÈΤ˜ ÛÙ· Ê¿Ú-̷η ÂÈÏË„›Â˜, ·È‰È΋ ËÏÈΛ·.

were observed in 10/17 patients (58.8%) andincluded weight loss and loss of appetite in 4,aggressiveness in 4, somnolence and difficulty inconcentration in 2 patients. As a conclusion,topiramate was shown to be quite effective andsafe as adjunctive therapy in 11/17 children andadolescents, with a wide range of cryptogenic andsymptomatic resistant epilepsies. Response ≥50%was observed in 64.7% of the children in the study.The drug was generally well tolerated and theadverse effects of the drug that were found in58.8% of the patients, were generally mild andtransient. Four patients withdrew from treatment(23.5%).

Key words: topiramate, drug resistant epilepsies,childhood.

™˘ÓÙÔÌÔÁڷʛ˜AEº ∞ÓÙÈÂÈÏËÙÈÎfi Ê¿ÚÌ·ÎÔAED Anti-epileptic drugKN™ ∫ÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ·CBZ ∫·Ú‚·Ì·˙›ÓËOXC OÍηڂ·˙›ÓËPHT º·ÈÓ˘ÙÔ˝ÓËVGB µÈÁη̷ÙÚ›ÓËLTG §·ÌÔÙÚÈÁ›ÓËCLB ∫ÏÔÌ·˙¿ÌËVPA µ·ÏÚÔ˚Îfi Ô͇ TGB ∆È·Áη̛ÓËPB º·ÈÓÔ‚·Ú‚ÈÙ¿ÏËETM ∞ÈıÔÛÔ˘ÍÈÌ›‰ËTPM ∆ÔÈÚ·Ì¿ÙËCORT ∫ÔÚÙÈÎÔÂȉ‹CLZ ∫ÏÔÓ·˙¿ÌËACTH ™˘ÓıÂÙÈ΋ ·‰ÚÂÓÔÎÔÚÙÈÎÔÙÚfiÔ˜ ÔÚÌfiÓË∂ ∂ÈÏË„›· æ∫∂ æ˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍËMRI ª·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘IVH ∂Ó‰ÔÎÔÈÏȷ΋ ·ÈÌÔÚÚ·Á›·GABA °¿Ì·-·ÌÈÓÔ-‚Ô˘Ù˘ÚÈÎfi Ô͇

∂ÈÛ·ÁˆÁ‹¶·Ú¿ ÙË ÛËÌ·ÓÙÈ΋ ÚfiÔ‰Ô ÛÙË ıÂڷ›· ÙˆÓ

ÂÈÏË„ÈÒÓ Ì ÙËÓ ÂÈÛ·ÁˆÁ‹ ÈηÓÔ‡ ·ÚÈıÌÔ‡ Ó¤ˆÓ∞∂º, ˘¿Ú¯ÂÈ ·ÎfiÌË ¤Ó· ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ·ÛıÂÓÒÓ(ÂÚ›Ô˘ 20%) Ô˘ ÂÌÊ·Ó›˙ÂÈ ·ÓıÂÎÙÈÎfiÙËÙ· ÛÙËÓ

·ÁˆÁ‹, ‰ËÏ·‰‹ ÂÈÌÔÓ‹ ÙˆÓ ÎÚ›ÛÂˆÓ ÌÂÙ¿ ·fi ÙÔ˘-Ï¿¯ÈÛÙÔÓ ‰‡Ô ¯ÚfiÓÈ· “ηϿ ·ÎÔÏÔ˘ıÔ‡ÌÂÓ˘” Ê·Ú-̷΢ÙÈ΋˜ ıÂڷ›·˜ Î·È Î·Ù¿ ηÓfiÓ· Ô‰ËÁ›ٷÈÛÙËÓ ÔÏ˘Ê·Ú̷Λ· (1). ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜, ËÚfiÁÓˆÛË ·Ú·Ì¤ÓÂÈ ‰˘ÛÌÂÓ‹˜, ȉȷ›ÙÂÚ· fiÙ·Ó Ô›‰ÈÔ˜ ·ÛıÂÓ‹˜ ·ÚÔ˘ÛÈ¿˙ÂÈ ÂÚÈÛÛfiÙÂÚÔ˘˜ ·fi ¤Ó·Ó‹ ÔÚÈṲ̂ÓÔ˘˜ ȉȷ›ÙÂÚÔ˘˜ Ù‡Ô˘˜ ÎÚ›ÛÂˆÓ (.¯. ÙÔÓÈ-Τ˜ ‹ ·ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ). ¶·ÚfiÌÔÈ·, Ë ·ÓıÂÎÙÈÎfiÙËÙ·ÛÙËÓ ·ÁˆÁ‹ Â›Ó·È Û˘Ó‹ı˘ ÁÈ· ÔÚÈṲ̂ӷ ÂÈÏËÙÈοۇӉÚÔÌ· (Û‡Ó‰ÚÔÌÔ Lennox-Gastaut, Û‡Ó‰ÚÔÌÔWest) ‹ ÂÍÂÏÈÎÙÈΤ˜ Ó¢ÚÔÏÔÁÈΤ˜ ·ı‹ÛÂȘ (.¯.ÚÔԉ¢ÙÈ΋ Ì˘ÔÎÏÔÓÈ΋ ÂÈÏË„›·), ·ÏÏ¿ Î·È ÁÈ· ÙȘÂÛÙȷΤ˜ ÎÚ›ÛÂȘ Ì ‹ ¯ˆÚ›˜ ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË(2,3). ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜, Ì ٷ ·ÓˆÙ¤Úˆ ÂÈÏË-ÙÈο Û‡Ó‰ÚÔÌ· Î·È ÂÈÏË„›Â˜, ÔÈ Ó¢ÚÔ·ÎÙÈÓÔÏÔÁÈ-Τ˜ ÂÍÂÙ¿ÛÂȘ ÌÔÚ› Ó· ‰Â›ÍÔ˘Ó ‰È¿¯˘Ù˜ ÂÁÎÂÊ·ÏÈ-Τ˜ ‹ ÂÛÙȷΤ˜ ‚Ï¿‚˜ ÙÔ˘ ∫¡™, ÂÓÒ Û˘¯Ó¿ ·Ú·ÙË-ÚÔ‡ÓÙ·È ‰È·Ù·Ú·¯¤˜ Û˘ÌÂÚÈÊÔÚ¿˜, Ô˘ ÌÂÚÈΤ˜ÊÔÚ¤˜ Û˘Óԉ‡ÔÓÙ·È Î·È ·fi ÓÔËÙÈ΋ ¤ÎÙˆÛË.

∏ ÙÔÈÚ·Ì¿ÙË Â›Ó·È ¤Ó· ∞∂º Ô˘ ¯ÚËÛÈÌÔÔÈ›ٷÈÛ ÂÓ‹ÏÈΘ Î·È ·È‰È¿ ËÏÈΛ·˜ ≥2 ÂÙÒÓ, ˆ˜ Û˘ÌÏË-ڈ̷ÙÈ΋ ıÂڷ›· Û ÂÛÙÈ·ÎÔ‡˜ Û·ÛÌÔ‡˜, Ì ‹¯ˆÚ›˜ ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË, ηıÒ˜ Î·È Û ·ÛıÂ-Ó›˜ Ô˘ ‰ÂÓ Ú˘ıÌ›˙ÔÓÙ·È Ì ٷ ÎÏ·ÛÈο AEº (4,5).¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ Ê¿ÚÌ·ÎÔ ÌÔ-Ú› Ó· Â›Ó·È ¯Ú‹ÛÈÌÔ Î·È Û ÔÏÏÔ‡˜ ¿ÏÏÔ˘˜ Ù‡Ô˘˜ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ ‹ ÂÈÏËÙÈÎÒÓ Û˘Ó‰ÚfiÌˆÓ (ÁÂ-ÓÈÎÂ˘Ì¤Ó˜ ÂÈÏË„›Â˜, ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜, Û‡Ó-‰ÚÔÌÔ Lennox-Gaustaut) (6-9).

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MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·108

∏ ÙÔÈÚ·Ì¿ÙË Î·Ù·Ù¿ÛÛÂÙ·È ¯ËÌÈο ÛÙÔ˘˜ÛÔ˘ÏÊ·Ì·ÙÔ-ÌÔÓÔ۷ί·Ú›Ù˜ Î·È ‰Ú· ΢ڛˆ˜ ̤-Ûˆ Ù˘ ·Ó·ÛÙÔÏ‹˜ Ù˘ ÂͿψÛ˘ Ù˘ ÂÈÏËÙÈ΋˜ÎÚ›Û˘, ·ÏÏ¿ Ù·˘Ùfi¯ÚÔÓ· ÌÔÚ› Ó· ·Ó‚¿˙ÂÈ Î·ÈÙÔÓ ÂÈÏËÙÈÎfi Ô˘‰fi. Œ¯ÂÈ ÔÏÏ·Ïfi Ì˯·ÓÈÛÌfi‰Ú¿Û˘ Î·È Ê·›ÓÂÙ·È fiÙÈ ·›˙ÂÈ Ú˘ıÌÈÛÙÈÎfi ÚfiÏÔÛÙÔ˘˜ ÂÓÂÚÁÔÔÈË̤ÓÔ˘˜ ‰È·‡ÏÔ˘˜ Ó·ÙÚ›Ô˘ (·Ô-ÎÏ›ÂÈ ÙÔ˘˜ ‰È·‡ÏÔ˘˜ Ù˘ ÓÂ˘ÚˆÓÈ΋˜ ÌÂÌ‚Ú¿Ó˘),ÛÙÔ˘˜ ‰È·‡ÏÔ˘˜ ·Û‚ÂÛÙ›Ô˘, ÛÙÔ˘˜ GABA ˘Ô‰Ô-¯Â›˜ (ÂÓÈÛ¯‡ÂÈ ÙË ‰Ú¿ÛË ÙÔ˘ GABA) Î·È ÛÙÔ˘˜Kainate/AMPA ˘Ô‰Ô¯Â›˜ (·ÓÙ·ÁˆÓ›˙ÂÙ·È ÙÔ ÁÏÔ˘-Ù·ÌÈÎfi Ô͇), Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ‰ÈÂ-ÁÂÚÙÈ΋˜ Ó¢ÚÔÌÂÙ·‚›‚·Û˘ (10,11).

™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Î·Ù·ÁÚ¿ÊÂÙ·È Ë ÂÌÂÈÚ›·Ù˘ Û˘ÁÎÂÎÚÈ̤Ó˘ ÎÏÈÓÈ΋˜ ·fi ÙË ¯Ú‹ÛË ÙÔ˘Ê·ÚÌ¿ÎÔ˘, ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋˜ ·ÁˆÁ‹˜, Û ·È-‰È¿ Î·È ÂÊ‹‚Ô˘˜ Ì ̷ÎÚfi¯ÚÔÓË ·ÓıÂÎÙÈ΋ ÂÈÏË-„›·. °›ÓÂÙ·È ·ÍÈÔÏfiÁËÛË Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÛÙË Ú‡ıÌÈÛË ÙˆÓ ÎÚ›ÛˆÓ, ηıÒ˜Î·È Ù˘ ·ÛÊ¿ÏÂÈ¿˜ ÙÔ˘ ÁÈ· ÙÔ˘˜ ÌÈÎÚÔ‡˜ ·ÛıÂÓ›˜.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ∆Ô ˘ÏÈÎfi Ù˘ ÌÂϤÙ˘ ·ÔÙ¤ÏÂÛ·Ó ·È‰È¿ Î·È ¤ÊË‚ÔÈ ÌÂ

Ì·ÎÚfi¯ÚÔÓË Î·È ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÈÏË„›·, Ì ̤ÛˉȿÚÎÂÈ· ÓfiÛÔ˘ Ù· 6,9 ¤ÙË Î·È Û˘¯ÓfiÙËÙ· ÎÚ›ÛÂˆÓ ·fi 1‚‰ÔÌ·‰È·›ˆ˜ ¤ˆ˜ 20 ÎÚ›ÛÂȘ ËÌÂÚËÛ›ˆ˜. ™ÙË ÌÂϤÙË Û˘Ì-ÌÂÙ›¯·Ó Û˘ÓÔÏÈο 17 ·È‰È¿, 11 ·ÁfiÚÈ· Î·È 6 ÎÔÚ›ÙÛÈ·. ∏ ËÏÈ-Λ· ÙÔ˘˜ Î˘Ì·ÈÓfiÙ·Ó Û 4,5-19 ¤ÙË (̤ÛË ËÏÈΛ·: 10,4 ¤ÙË) ηÈÔÈ ÎÚ›ÛÂȘ Û 5 ·È‰È¿ (30%) ›¯·Ó ¤Ó·ÚÍË ÛÙÔÓ ÚÒÙÔ ¯Úfi-ÓÔ Ù˘ ˙ˆ‹˜. H ‰È¿ÁÓˆÛË ‚·Û›ÛÙËΠ۠ÎÏÈÓÈο, ËÏÂÎÙÚÔ-ÂÁÎÂÊ·ÏÔÁÚ·ÊÈο Î·È Ó¢ÚÔ-·ÂÈÎÔÓÈÛÙÈο (MRI) ‰Â‰Ô̤ӷ.

∏ ηٿٷÍË ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Î·È ÂÈÏËÙÈÎÒÓ Û˘Ó-‰ÚfiÌˆÓ ¤ÁÈÓ ۇÌʈӷ Ì ÙËÓ Ù·ÍÈÓfiÌËÛË Ù˘ ¢ÈÂıÓÔ‡˜ ŒÓˆ-Û˘ ηٿ Ù˘ ∂ÈÏË„›·˜ (ILAE, 1989) (12). ™‡Ìʈӷ Ì ·˘Ù‹,11/17 ·ÛıÂÓ›˜ (64,7% ÙÔ˘ Û˘ÓfiÏÔ˘) ›¯·Ó Û˘Ìو̷ÙÈ΋ ·È-ÙÈÔÏÔÁ›·, ‰ËÏ·‰‹ Ë ·ÈÙÈÔÏÔÁ›· Ù˘ ÓfiÛÔ˘ ‹Ù·Ó ÁÓˆÛÙ‹ Ì ÙË‚Ô‹ıÂÈ· ÙÔ˘ ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂϤÁ¯Ô˘ (˘‹Ú¯Â ˘ÔΛÌÂÓË ‰È¿-¯˘ÙË ‹ ÂÛÙȷ΋ ‚Ï¿‚Ë ÙÔ˘ ∫¡™). ™Â Û˘Ó¿ÚÙËÛË Ì ÙËÓ ÂÓÙfiÈ-ÛË Ù˘ ÓfiÛÔ˘, ÔÈ 11 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ ›¯·Ó ÂÛÙȷ΋ ÂÈ-ÏË„›· (8 Û˘Ìو̷ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹) Î·È ÔÈ ˘fiÏÔÈÔÈ 6 ÁÂ-ÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· (3 Û˘Ìو̷ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹). ∞Ó·ÊÔ-ÚÈο, Ù¤ÏÔ˜, Ì ÙÔ Â›‰Ô˜ ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛˆÓ, ·fi ÙÔ˘˜11 ·ÛıÂÓ›˜ Ì ÂÛÙȷ΋ ÂÈÏË„›· ÔÈ 8 ÂÌÊ¿ÓÈ˙·Ó Û‡ÓıÂÙ˜ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, ÔÈ 5 Î·È Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË Î·È ÔÈ 3ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, ÔÈ 2 Î·È Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË, ›Û˘.∞fi ÙÔ˘˜ 6 ·ÛıÂÓ›˜ Ì ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›·, 1 ÂÌÊ¿ÓÈ˙ ÁÂ-ÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ, 1 Ì˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ,1 ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜ ·Ú¯Èο, Ô˘ ÛÙË Û˘Ó¤¯ÂÈ· ÂÍÂÏ›¯ıËηÓÛ ۇӉÚÔÌÔ Lennox-Gastaut ηÈ, Ù¤ÏÔ˜, 3 ·ÛıÂÓ›˜ ›¯·ÓÛ‡Ó‰ÚÔÌÔ Lennox-Gastaut (ÎÚ›ÛÂȘ ÙÔÓÈΤ˜, ·ÙÔÓÈΤ˜, ¿Ù˘Â˜·Ê·ÈÚ¤ÛÂȘ Î·È Ì˘ÔÎÏÔӛ˜). ™˘ÓÔÏÈο ‰Â, 8/17 ·ÛıÂÓ›˜ ›¯·Ó¿Óˆ ·fi ¤Ó·Ó Ù‡Ô ÎÚ›ÛˆÓ.

™ÙÔÓ ¶›Ó·Î· 1 ·Ó·ÁÚ¿ÊÔÓÙ·È ·Ó·Ï˘ÙÈο Ë ËÏÈΛ· ¤Ó·Ú-͢ Î·È ÔÈ Ù‡ÔÈ ÙˆÓ ÎÚ›ÛˆÓ, Ô ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ηÈ

109

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Ù· ÂÈÏËÙÈο Û‡Ó‰ÚÔÌ·, fiÔ˘ ηٷٿ¯ıËÎ·Ó ÔÈ ·ÛıÂÓ›˜.™ËÌÂÈÒÓÔÓÙ·È Â›Û˘ Î·È Ù· Û˘Ó˘¿Ú¯ÔÓÙ· ·Ó·Ù˘Íȷο ηÈÓ¢ÚÔÏÔÁÈο ÚÔ‚Ï‹Ì·Ù· ÙˆÓ ·ÛıÂÓÒÓ, ηıÒ˜ 10 ·ÛıÂÓ›˜·ÚÔ˘Û›·˙·Ó οÔÈÔ˘ ‚·ıÌÔ‡ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË (4 ÛÔ‚·Ú‹,3 ̤ÙÚÈ·, 3 ‹È·) Ô˘ ·ÍÈÔÏÔÁ‹ıËΠ̠ÙÔÓ ¤ÏÂÁ¯Ô ÙÔ˘ ‰Â›-ÎÙË ÓÔËÌÔÛ‡Ó˘, Ì ÙȘ ‰ÔÎÈ̷ۛ˜ Standford - Binet ηÈWeschler (·Ó·ÏfiÁˆ˜ Ù˘ ËÏÈΛ·˜ ÙÔ˘˜) Î·È 6 ÂÌÊ¿ÓÈ˙·Ó ÂÁÎÂ-Ê·ÏÈ΋ ·Ú¿Ï˘ÛË (3 ËÌÈÏËÁ›·, 2 ÙÂÙÚ·ÏËÁ›·, 1 ·Ù·Í›·).∞Ôχو˜ Ê˘ÛÈÔÏÔÁÈ΋ ÓÔËÌÔÛ‡ÓË Î·È Ó¢ÚÔÏÔÁÈ΋ ÂÈÎfiÓ·ÂÌÊ¿ÓÈ˙·Ó 5 ÌfiÓÔÓ ·fi ÙÔ˘˜ 17 ·ÛıÂÓ›˜.

∫·Ù¿ ÙËÓ ¤Ó·ÚÍË ¯ÔÚ‹ÁËÛ˘ Ù˘ ÙÔÈÚ·Ì¿Ù˘, fiÏÔÈ ÔÈ·ÛıÂÓ›˜ ÂÏ¿Ì‚·Ó·Ó 1-4 ¿ÏÏ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η, Ù·ÔÔ›· ·Ó·ÁÚ¿ÊÔÓÙ·È ·Ó·Ï˘ÙÈο ÛÙÔÓ ¶›Ó·Î· 2. ŸÏ· Ù· ·È-‰È¿ Ì ÂÛÙȷ΋ ÂÈÏË„›· ›¯·Ó Ï¿‚ÂÈ ÚÔËÁÔ˘Ì¤Óˆ˜ ηڂ·-Ì·˙›ÓË, ÔÍηڂ·˙›ÓË, Ê·ÈÓ˘ÙÔ˝ÓË, ‚ÈÁη̷ÙÚ›ÓË, Ï·ÌÔ-ÙÚÈÁ›ÓË, ÎÏÔÌ·˙¿ÌË, ÂÓÒ Ù· ·È‰È¿ Ì ÁÂÓÈÎÂ˘Ì¤Ó· ÂÈÏËÙÈ-ο Û‡Ó‰ÚÔÌ· ›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ ‚·ÏÚÔ˚Îfi, Ï·ÌÔÙÚÈÁ›ÓË Î·ÈÎÏÔÌ·˙¿ÌË Û ÌÔÓÔıÂڷ›· ‹ Î·È Û˘Ó‰˘·ÛÌÔ‡˜. ∂›Û˘,ÌÂÚÈο ·È‰È¿ ›¯·Ó ·ÓÙÈÌÂÙˆÈÛÙ› Î·È Ì ¿ÏÏ· ·ÓÙÈÂÈÏËÙÈ-ο Ê¿Ú̷η, fiˆ˜ ÙÈ·Áη̛ÓË, Ê·ÈÓÔ‚·Ú‚ÈÙ¿ÏË, ·ÈıÔÛÔ˘-ÍÈÌ›‰Ë, ÎÏÔÓ·˙¿ÌË, ÎÔÚÙÈÎÔÂȉ‹ ‹ ACTH ‹ Î·È Á-ÛÊ·ÈÚ›ÓË(¶›Ó·Î·˜ 2).

∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ (ÂχıÂÚÔÈ ÎÚ›ÛˆÓ,Ì›ˆÛË ÎÚ›ÛÂˆÓ >75%, Ì›ˆÛË ÎÚ›ÛÂˆÓ >50%, Ì›ˆÛË ÎÚ›ÛÂ-ˆÓ <50%, η̛· ·ÓÙ·fiÎÚÈÛË, ·‡ÍËÛË ÙˆÓ ÎÚ›ÛˆÓ-Âȉ›ӈ-ÛË) ÂÎÙÈÌ‹ıËΠÚÈÓ ÙËÓ ¤Ó·ÚÍË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È 5-15 Ì‹Ó˜·ÚÁfiÙÂÚ· (̤ÛË ·Ú·ÎÔÏÔ‡ıËÛË: 7 Ì‹Ó˜). °È· ÙËÓ ÂÎÙ›ÌËÛËÙ˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÎÚ›ÛÂˆÓ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ËÌÂÚÔÏfiÁȷηٷÁÚ·Ê‹˜ (ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô Î·È ·fi ÙÔ˘˜ ÁÔÓ›˜, ÛÙÔ Û›ÙÈ)Î·È Ù·ÎÙÈ΋ ÌËÓÈ·›· ÂÓ‰ÔÓÔÛÔÎÔÌÂȷ΋ ÎÏÈÓÈ΋ (Î·È ÂÈÏÂÎÙÈÎ¿Î·È ËÏÂÎÙÚÔ-ÂÁÎÂÊ·ÏÔÁÚ·ÊÈ΋) ·Ú·ÎÔÏÔ‡ıËÛË.

∏ ÙÔÈÚ·Ì¿ÙË ÚÔÛÙ¤ıËΠÛÙËÓ ÚÔ¸¿Ú¯Ô˘Û· ·ÁˆÁ‹,Û ‰fiÛË ¤Ó·Ú͢ 1 mg/kg/24 h. ∞ÎÔÏÔ‡ıˆ˜, ¤ÁÈÓ ÛÙ·‰È·Î‹·‡ÍËÛË Ù˘ ‰fiÛ˘ (1 mg/kg/24 h ·Ó¿ 2 ‚‰ÔÌ¿‰Â˜), ·Ó¿ÏÔ-Á· Ì ÙËÓ ·ÓÙ·fiÎÚÈÛË ÙˆÓ ·ÛıÂÓÒÓ, Û 3-10 mg/kg/24 h. ∏‰fiÛË ÛÙfi¯Ô˜ ‹Ù·Ó 10 mg/kg/24 h ÁÈ· ·È‰È¿ ÌÈÎÚfiÙÂÚ· ÙˆÓ8 ÂÙÒÓ Î·È 5-8 mg/kg/Ë̤ڷ ÁÈ· Ù· ·È‰È¿ ÌÂÁ·Ï‡ÙÂÚ˘ ËÏÈ-Λ·˜. ™ÙÔÓ ÏËı˘ÛÌfi Ù˘ ÌÂϤÙ˘ ‰ÂÓ ¤ÁÈÓ ̤ÙÚËÛË ÙˆÓ ÂÈ-¤‰ˆÓ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÛÙÔ Ï¿ÛÌ·.

∞ÔÙÂϤÛÌ·Ù· ∞fi ÙÔ˘˜ 17 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘, ÔÈ 11

(64,7%) ÂÌÊ¿ÓÈÛ·Ó ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÂÈÏË-ÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi ≥50% (Ô˘ ıˆÚ›ٷÈÎÚÈÙ‹ÚÈÔ ÈηÓÔÔÈËÙÈ΋˜ Ú‡ıÌÈÛ˘ ÁÈ· ÙȘ ·ÓıÂÎÙÈ-Τ˜ ÂÈÏË„›Â˜), ÂÓÒ 6 ·fi ·˘ÙÔ‡˜ ··ÏÏ¿¯ÙËηÓÏ‹Úˆ˜ (35,2%). ∞Ó·Ï˘ÙÈÎfiÙÂÚ·, ÛÙÔ˘˜ 6 ·ÛıÂÓ›˜Ô˘ ÔÈ ÂÈÏËÙÈΤ˜ ÎÚ›ÛÂȘ ÂϤÁ¯ıËÎ·Ó Ï‹Úˆ˜, ÔÈ2 ›¯·Ó Û‡Ó‰ÚÔÌÔ Lennox-Gastaut (1 Û˘Ìو̷ÙÈ-Îfi, 1 ÎÚ˘ÙÔÁÂÓ¤˜), ÔÈ 3 ÂÛÙȷ΋ ÂÈÏË„›· (1 Û˘-Ìو̷ÙÈ΋, 2 ÎÚ˘ÙÔÁÂÓ‹) Î·È 1 ›¯Â ÎÚ˘ÙÔÁÂÓ‹ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›·.

™ÙÔ˘˜ ˘fiÏÔÈÔ˘˜ 5 ·ÛıÂÓ›˜, Ì›ˆÛË ÙˆÓ ÎÚ›-ÛÂˆÓ Û ÔÛÔÛÙfi >75% ·Ú·ÙËÚ‹ıËΠ۠4 ·ÛıÂ-

Ó›˜, Ô˘ fiÏÔÈ Â›¯·Ó Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË-„›· Î·È Ì›ˆÛË Û ÔÛÔÛÙfi >50% ·Ú·ÙËÚ‹ıËÎÂÛ 1 ·ÛıÂÓ‹ ÌÂ Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË„›·,›Û˘. ¶ÂÚÈÔÚÈṲ̂ÓË ·¿ÓÙËÛË ÛÙËÓ ·ÁˆÁ‹ ÌÂÂÏ¿ÙÙˆÛË ÙˆÓ ÎÚ›ÛÂˆÓ <50% ÂÌÊ¿ÓÈÛ·Ó 2 ·ÛıÂ-Ó›˜, ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ 1 ›¯Â ‚ÚÂÊÈÎÔ‡˜ Û·-ÛÌÔ‡˜, Ô˘ ›¯·Ó ÌÂÙÂÍÂÏȯı› Û ۇӉÚÔÌÔLennox-Gastaut Î·È 1 ›¯Â Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ÂÈÏË„›·.

™˘ÓÔÙÈο, fiÛÔÓ ·ÊÔÚ¿ ÛÙ· ÂÈÏËÙÈο Û‡Ó-‰ÚÔÌ·, Ë ÙÔÈÚ·Ì¿ÙË ˘‹ÚÍ ·ÔÙÂÏÂÛÌ·ÙÈ΋ (Ì›-ˆÛË ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi >50%) ÛÙÔ˘˜ 8/11 ·ÛıÂ-Ó›˜ Ì ÔÔÈ·Û‰‹ÔÙ ÌÔÚÊ‹˜ ‹ ·ÈÙÈÔÏÔÁ›·˜ ÂÛÙÈ·-΋ ÂÈÏË„›·, ÛÙÔÓ 1 ·fi ÙÔ˘˜ 2 ·ÛıÂÓ›˜ Ì ÁÂÓÈ-ÎÂ˘Ì¤ÓË ÂÈÏË„›· Î·È ÛÙÔ˘˜ 2 ·fi ÙÔ˘˜ 3 ·ÛıÂÓ›˜Ì ۇӉÚÔÌÔ Lennox-Gastaut.

∫·Ì›· ·ÏÏ·Á‹ ÛÙË Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÈÏËÙÈÎÒÓÎÚ›ÛÂˆÓ ‰ÂÓ ·ÚÔ˘Û›·Û·Ó 3 ·ÛıÂÓ›˜: 1 Ì ÎÚ˘-ÙÔÁÂÓ¤˜ Û‡Ó‰ÚÔÌÔ Lennox-Gastaut, 1 ÌÂ Û˘ÌÙˆ-Ì·ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË„›· Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢-ÛË Î·È 1 ÌÂ Û˘Ìو̷ÙÈ΋ ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· ÌÂÌ˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ. ∆¤ÏÔ˜, Âȉ›ӈÛË ÙˆÓÎÚ›ÛÂˆÓ ·Ú·ÙËÚ‹ıËΠ۠1 ÌfiÓÔ ·ÛıÂÓ‹ Ì ÎÚ˘-ÙÔÁÂÓ‹ Û‡ÓıÂÙË ÂÛÙȷ΋ ÂÈÏË„›· (¶›Ó·Î·˜ 2).™ÙÔ˘˜ 4 ÙÂÏÂ˘Ù·›Ô˘˜ ·ÛıÂÓ›˜ (23,5%) Ë ·ÁˆÁ‹‰È·ÎfiËÎÂ.

™ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ·ÓÙ·ÔÎÚ›ıËÎ·Ó ÛÙËÓ ÚÔ-Ûı‹ÎË Ù˘ ÙÔÈÚ·Ì¿Ù˘, ‰ÂÓ ¤ÁÈÓÂ Û˘ÛÙËÌ·ÙÈ΋ÚÔÛ¿ıÂÈ· Ó· ÂÈÙ¢¯ı› ÌÔÓÔıÂڷ›·. ∂ÓÙÔ‡-ÙÔȘ, Û 2 ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ η٤ÛÙˉ˘Ó·Ùfi Ó· ÂÏ·ÙÙˆıÔ‡Ó ÔÈ ‰fiÛÂȘ ÙˆÓ Û˘Á¯ÔÚËÁÔ‡-ÌÂÓˆÓ AEº.

¶·ÚÂÓ¤ÚÁÂȘ ÂÌÊ¿ÓÈÛ·Ó 10/17 ·ÛıÂÓ›˜(58,8%) (¶›Ó·Î·˜ 2). ∆¤ÛÛÂÚȘ ·ÛıÂÓ›˜ ·ÚÔ˘Û›·-Û·Ó ÂÚÈÛÛfiÙÂÚ˜ ·fi Ì›· ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂÈ-˜. ™ÙËÓ ÏÂÈÔ„ËÊ›· ÙÔ˘˜ ÔÈ ·ÚÂÓ¤ÚÁÂȘ ‹Ù·Ó‹È˜ Î·È ·ÚÔ‰ÈΤ˜. ∏ ÈÔ Û˘Ó‹ı˘ ‹Ù·Ó Ë ·ÓÔÚÂ-Í›· (4 ·ÛıÂÓ›˜), Ë ÔÔ›· ‹Ù·Ó ·ÚÔ‰È΋, ÛÙËÓ ·Ú-¯È΋ Ê¿ÛË ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È ÛÙÔ˘˜ ÌÈ-ÎÚfiÙÂÚ˘ ËÏÈΛ·˜ ·ÛıÂÓ›˜, ÌÂ Û˘ÓÔ‰fi ÌÈÎÚ‹ ·Ò-ÏÂÈ· ‚¿ÚÔ˘˜ (<0,5 kg). ™ËÌ·ÓÙÈ΋ ·ÒÏÂÈ· ‚¿ÚÔ˘˜(>5 kg) ·Ú·ÙËÚ‹ıËΠÌfiÓÔ Û 1 Ó·Úfi ÂÓ‹ÏÈη 19ÂÙÒÓ. ∏ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ·Ú·ÙËÚ‹ıËΠÛÙÔ ÚÒ-ÙÔ ÙÚ›ÌËÓÔ ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘, ÂÓÒ ÛÙË Û˘-Ó¤¯ÂÈ· ÙÔ ‚¿ÚÔ˜ ÙÔ˘ ÛÙ·ıÂÚÔÔÈ‹ıËÎÂ.

¶·ÚÂÓ¤ÚÁÂȘ Ô˘ Ó· Ô‰‹ÁËÛ·Ó Û ‰È·ÎÔ‹ ÙÔ˘Ê·ÚÌ¿ÎÔ˘, ÛÂ Û˘Ó¿ÚÙËÛË Î·È Ì ÙË ÌË Ú‡ıÌÈÛËÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛˆÓ, ·Ú·ÙËÚ‹ıËÎ·Ó Û 3·ÛıÂÓ›˜. ¢‡Ô ·ÛıÂÓ›˜ ÂÌÊ¿ÓÈÛ·Ó ÂÍ·ÈÚÂÙÈ΋ ÂÈ-ıÂÙÈÎfiÙËÙ· (1 Ì ۇӉÚÔÌÔ Lennox-Gastaut Î·È 1Ì ÁÂÓÈÎÂ˘Ì¤ÓË Û˘Ìو̷ÙÈ΋ ÂÈÏË„›·, ÏfiÁˆ Û˘Ó-‰ÚfiÌÔ˘ Angelman) Î·È Ô ÙÚ›ÙÔ˜ ·ÚÔ˘Û›·Û ¤ÓÙÔ-ÓË ˘ÓËÏ›· Î·È ‰È·Ù·Ú·¯‹ Ù˘ Û˘ÁΤÓÙÚˆÛ˘(·ÛıÂÓ‹˜ ÌÂ Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË„›·).

¶·È‰È·ÙÚÈ΋ 2003;66:104-112 Paediatriki 2003;66:104-112

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¶·È‰È·ÙÚÈ΋ 2003;66:104-112 Paediatriki 2003;66:104-112

™˘˙‹ÙËÛË ∏ ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹ ÛÙËÓ ÂÈÏË„›· ¤¯ÂÈ Û·Ó

·ÚÈÔ ÛÙfi¯Ô ÙËÓ ··ÏÏ·Á‹ ÙˆÓ ·ÛıÂÓÒÓ ·fi ÙȘÎÚ›ÛÂȘ, ·ÏÏ¿ Î·È ÙË ‚ÂÏÙ›ˆÛË ÙˆÓ Û¯ÂÙÈ˙fiÌÂÓˆÓ Ì·˘Ù‹ ‰È·Ù·Ú·¯ÒÓ (ÓÔËÙÈÎÒÓ, Ó¢ÚÔÏÔÁÈÎÒÓ Î·È Û˘-ÌÂÚÈÊÔÚ¿˜) Ô˘ ÂȉÂÈÓÒÓÔ˘Ó ÙË ÁÂÓÈ΋ ηٿÛÙ·-ÛË ÙÔ˘ ·ÛıÂÓÔ‡˜. ™Â ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜, fï˜,fiˆ˜ Ô ÂÈÏÂÁ̤ÓÔ˜ ÏËı˘ÛÌfi˜ Ù˘ ÌÂϤÙ˘ Ì·˜(·È‰È¿ Î·È ¤ÊË‚ÔÈ Ì ·ÓıÂÎÙÈ΋ ÂÈÏË„›·), Ô˘Û¯Â‰fiÓ fiÏÔÈ ˘Ô‚¿ÏÏÔÓÙ·Ó Û ÔÏ˘ıÂڷ›· ηÈÛ ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi (59%) ›¯·Ó Î·È ÓÔËÙÈ΋˘ÛÙ¤ÚËÛË ‹ ¿ÏÏ· ÛËÌ·ÓÙÈο Ó¢ÚÔÏÔÁÈο ÚÔ‚Ï‹-Ì·Ù· (ÂÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË, Û‡Ó‰ÚÔÌÔ ÂÏÏÂÈÌÌ·-ÙÈ΋˜ ÚÔÛÔ¯‹˜ Î·È ˘ÂÚÎÈÓËÙÈÎfiÙËÙ·˜ Î.Ï.) ‰ÂÓÂ›Ó·È Û˘Ó‹ıˆ˜ ‰˘Ó·Ù‹ Ë Ï‹Ú˘ ··ÏÏ·Á‹ ·fi ÙȘÎÚ›ÛÂȘ. ŒÙÛÈ, Ô ıÂڷ¢ÙÈÎfi˜ ÛÙfi¯Ô˜ ÂÚÈÔÚ›˙ÂÙ·ÈÛÙË Ì›ˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÎÚ›ÛˆÓ, Û ›-‰· Ô˘ Ó· ÂÚÈÔÚ›˙Ô˘Ó ÙȘ ÛËÌ·ÓÙÈΤ˜ ‚Ï·ÙÈΤ˜ÂȉڿÛÂȘ Ù˘ ÂÈÏË„›·˜ (Û˘Ó‹ıˆ˜, Ë Ì›ˆÛË ÛÂÔÛÔÛÙfi ≥50% ıˆÚÂ›Ù·È ÈηÓÔÔÈËÙÈ΋ Ú‡ıÌÈÛË).

∞fi ÙË ÌÂϤÙË Ê¿ÓËΠfiÙÈ Ë ÙÔÈÚ·Ì¿ÙË ˘‹Ú-Í ·ÔÙÂÏÂÛÌ·ÙÈ΋ Û·Ó Û˘ÌÏËڈ̷ÙÈ΋ ·ÁˆÁ‹Û ·ÚÎÂÙ¿ ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ·ÛıÂÓÒÓ (64,7% ÙˆÓ·ÛıÂÓÒÓ, ›¯Â Ì›ˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÂÈÏË-ÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi ≥50%). ∂›Û˘, ÛËÌ·-ÓÙÈÎfi ‹Ù·Ó Î·È ÙÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ··Ï-Ï¿¯ıËÎ·Ó Ï‹Úˆ˜ ·fi ÙȘ ÎÚ›ÛÂȘ (6 ·ÛıÂÓ›˜ ‹ÔÛÔÛÙfi 35,2% ÙÔ˘ Û˘ÓfiÏÔ˘). ¶·ÚfiÌÔÈ· ·ÔÙÂϤ-ÛÌ·Ù· ÚԤ΢„·Ó ·fi Ì›· ·Ó¿ÏÔÁË ÌÂϤÙË Ô˘‰ÈÂÍ‹¯ıË ÛÙÔ ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ¶ÂÓÙ¤Ï˘, fiÔ˘ÙÔ ˘ÏÈÎfi (14 ·ÛıÂÓ›˜) ‹Ù·Ó ·Ó¿ÏÔÁÔ Ì ·˘Ùfi Ù˘·ÚÔ‡Û·˜ ÌÂϤÙ˘. ™ÙË ÌÂϤÙË ·˘Ù‹, ‚ÂÏÙ›ˆÛË ÛÂÔÛÔÛÙfi ≥50% ÂÌÊ¿ÓÈÛ ÙÔ 64,2% ÙˆÓ ·È‰ÈÒÓ,ÂÓÒ ÙËÓ ·ÁˆÁ‹ ‰È¤ÎÔ„·Ó ÙÚÂȘ ·ÛıÂÓ›˜, ÏfiÁˆ ÌË·ÓÙ·fiÎÚÈÛ˘ ‹ ¤ÓÙÔÓ˘ „˘¯ÔÎÈÓËÙÈ΋˜ ÂÈ‚Ú¿-‰˘ÓÛ˘ (13). ∂›Û˘, ÔÈ Yeung Î·È Û˘Ó, ÛÙË ÌÂϤÙËÙÔ˘˜ Ì 34 ·ÛıÂÓ›˜ Ì ·ÓıÂÎÙÈ΋ ÂÈÏË„›· ÔÈΛ-ÏˆÓ Ù‡ˆÓ, ¤Ù˘¯·Ó Ì ÙË ¯Ú‹ÛË Ù˘ ÙÔÈÚ·Ì¿Ù˘Ì›ˆÛË ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi≥50%, ÛÙÔ 58,8% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ·ÛıÂÓÒÓ (14).

∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ¤¯ÂÈ Ï¤-ÔÓ ·Ô‰Âȯı› ÛÙÔ˘˜ ÂÚÈÛÛfiÙÂÚÔ˘˜ Ù‡Ô˘˜ ÂÈÏË-„ÈÒÓ Î·È ÂÈÏËÙÈÎÒÓ Û˘Ó‰ÚfïÓ.

™Â ‰ÈϤ˜-Ù˘ÊϤ˜, ÂÏÂÁ¯fiÌÂÓ˜ Ì placebo ÌÂ-ϤÙ˜ ÙˆÓ Elterman Î·È Û˘Ó, Ô˘ ·ÊÔÚÔ‡Û·Ó ·Ô-ÎÏÂÈÛÙÈο Û ÂÛÙȷΤ˜ ÂÈÏË„›Â˜, ‰È·ÈÛÙÒıËΠ̛-ˆÛË ÙˆÓ Û·ÛÌÒÓ Û ÔÛÔÛÙfi ≥75%, ÛÙÔ 22%Ù˘ ÔÌ¿‰·˜ Ù˘ ÙÔÈÚ·Ì¿Ù˘, ¤Ó·ÓÙÈ ÙÔ˘ 2% Ù˘ÔÌ¿‰·˜ placebo (4). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, Ë ÙÔÈ-Ú·Ì¿ÙË ·Ô‰Â›¯ıËΠ›Û˘ Ôχ ¯Ú‹ÛÈÌÔ Ê¿ÚÌ·-ÎÔ ÛÙȘ ÂÛÙȷΤ˜ ÂÈÏË„›Â˜, ·ÊÔ‡ ηÙfiÚıˆÛ ˆ˜Û˘ÌÏËڈ̷ÙÈ΋ ·ÁˆÁ‹ Ó· ÌÂÈÒÛÂÈ ÛËÌ·ÓÙÈο ÙȘÎÚ›ÛÂȘ (>50%) ÛÙÔ 73% ·˘ÙÒÓ, ·ÓÂÍ·Úًو˜ Ù˘˘ÔΛÌÂÓ˘, Û ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi, Û˘Ìو̷ÙÈ-

΋˜ ÙÔ˘˜ ·ÈÙÈÔÏÔÁ›·˜. πηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù· ˘¿Ú¯Ô˘Ó Î·È ·fi

·ÓÙ›ÛÙÔȯ˜ ¤Ú¢Ó˜ Û ·ÛıÂÓ›˜ Ì ÁÂÓÈÎÂ˘Ì¤Ó˜ÂÈÏË„›Â˜ (6), Ì ۇӉÚÔÌÔ Lennox-Gastaut (8,9) ηÈÌ ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜ (7). ™Â ÚfiÛÊ·Ù˜, Ì¿ÏÈ-ÛÙ·, ÌÂϤÙ˜ ÚÔÙ›ÓÂÙ·È Ë ¯Ú‹ÛË Ù˘ ÙÔÈÚ·Ì¿Ù˘ˆ˜ Ê·ÚÌ¿ÎÔ˘ ÚÒÙ˘ ÂÈÏÔÁ‹˜ Î·È ˆ˜ ÌÔÓÔıÂÚ·-›·˜ Û ڈÙԉȷÁÓˆṲ̂Ó˜ ÂÈÏË„›Â˜, ÈÛfiÙÈÌ˘ÙÔ˘Ï¿¯ÈÛÙÔÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Ì ÙÔ ‚·ÏÚÔ˚ÎfiÓ¿ÙÚÈÔ Î·È ÙËÓ Î·Ú‚·Ì·˙›ÓË (15).

ŸÛÔÓ ·ÊÔÚ¿ ÛÙÔ Û‡Ó‰ÚÔÌÔ Lennox-Gastaut, Ù··ÔÙÂϤÛÌ·Ù· ‹Ù·Ó ıÂÙÈο Î·È ÛÙËÓ ·ÚÔ‡Û· ÌÂϤ-ÙË, ·ÊÔ‡ 2 ·fi ÙÔ˘˜ 3 ·ÛıÂÓ›˜ ··ÏÏ¿¯ıËÎ·Ó Ï‹-Úˆ˜ ·fi ÙȘ ÂÈÏËÙÈΤ˜ ÎÚ›ÛÂȘ, ÂÓÒ ÛÙË ÌÔÓ·‰È΋ÂÚ›ÙˆÛË ‚ÚÂÊÈÎÒÓ Û·ÛÌÒÓ Ô˘ ·ÓÙÈÌÂÙˆ›ÛÙË-ÎÂ Î·È Â›¯Â ÌÂÙÂÍÂÏȯı› ÛÙË Û˘Ó¤¯ÂÈ· Û ۇӉÚÔÌÔLennox-Gastaut, Ë ·¿ÓÙËÛË ‹Ù·Ó ÌÈÎÚ‹ (Ì›ˆÛËÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi <50%).

ŸÛÔÓ ·ÊÔÚ¿ ÛÙȘ ÁÂÓÈÎÂ˘Ì¤Ó˜ ÂÈÏË„›Â˜, ˘‹Ú-¯Â Ôχ ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ·ÛıÂÓÒÓ, ÁÈ· Ó· ‰È·Ù˘ˆı›ÔÔÈ·‰‹ÔÙ ¿Ô„Ë Î·È ·Ú·ÙËÚ‹ıËΠÙÂÏ›ˆ˜ ‰È·-ÊÔÚÂÙÈ΋ ·ÓÙ·fiÎÚÈÛË ÌÂٷ͇ ÙˆÓ 2 ·ÛıÂÓÒÓ Ù˘ÌÂϤÙ˘. O ¤Ó·˜ ·ÓÙ·ÔÎÚ›ıËΠϋڈ˜, ÂÓÒ Ô ‰Â‡-ÙÂÚÔ˜ ‰ÂÓ ·ÓÙ·ÔÎÚ›ıËΠηıfiÏÔ˘. ¶ÚfiÎÂÈÙ·È ÁÈ··ÛıÂÓ‹ ÌÂ Ì˘ÔÎÏÔÓÈ΋ ·Ê·ÈÚÂÙÈ΋ ÂÈÏË„›·, Ô˘ Û˘-ÌÂÚÈʤÚıËΠ·Ó¿ÏÔÁ· Ì ·ÛıÂÓ‹ Ì ›‰ÈÔ Ù‡Ô ÂÈ-ÏË„›·˜ ÛÙË ÌÂϤÙË ÙˆÓ Yeung Î·È Û˘Ó (14).

OÈ Î˘ÚÈfiÙÂÚ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Ô˘ ·-Ú·ÙËÚ‹ıËÎ·Ó ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘, ‹Ù·Ó Ë·ÓÔÚÂÍ›·, Ë ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Î·È ÔÈ ‰È·Ù·Ú·¯¤˜·fi ÙÔ ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ· (∫¡™) (΢ڛˆ˜Î·Ù·ÛÙÔÏ‹ Î·È ÚÔ‚Ï‹Ì·Ù· Û˘ÁΤÓÙÚˆÛ˘).

∏ ·ÓÔÚÂÍ›· ·ÊÔÚÔ‡Û ΢ڛˆ˜ Û ·ÛıÂÓ›˜ ÌÈ-ÎÚ‹˜ ËÏÈΛ·˜, ‹Ù·Ó ·ÚÔ‰È΋ Î·È ‰ÂÓ Ô‰‹ÁËÛ ÛÂÛËÌ·ÓÙÈ΋ ·ÒÏÂÈ· ‚¿ÚÔ˘˜, ÂÓÒ ÂÌÊ·Ó›ÛÙËΠÌfi-ÓÔ ÛÙËÓ ¤Ó·ÚÍË Ù˘ ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘. ™Â¿ÏϘ ‰ÈϤ˜ Ù˘ÊϤ˜ ÌÂϤÙ˜, ÂÓÒ Ë ·ÓÔÚÂÍ›· ·-Ú·ÙËÚ‹ıËΠÛÙÔ ›‰ÈÔ ÔÛÔÛÙfi ÌÂٷ͇ ·ÛıÂÓÒÓÔ˘ ¤·ÈÚÓ·Ó ÙÔÈÚ·Ì¿ÙË ‹ placebo ıÂڷ›· (4),Ë ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ‹Ù·Ó ·ÚÎÂÙ¿ ÈÔ ÛËÌ·ÓÙÈ΋ÛÙËÓ ÔÌ¿‰· Ù˘ ÙÔÈÚ·Ì¿Ù˘. ◊Ù·Ó fï˜ Û˘Ó‹-ıˆ˜ ÌÈÎÚ‹, ÂÌÊ·ÓÈ˙fiÙ·Ó ÙÔ˘˜ ÚÒÙÔ˘˜ 12-18 Ì‹-Ó˜ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ·ÎÔÏÔ˘ıÔ‡Û ·ӿÎÙËÛËÙÔ˘ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ‚¿ÚÔ˘˜, ¯ˆÚ›˜ Ó· ÂËÚ¿˙ÂÙ·ÈÌ·ÎÚÔ¯ÚfiÓÈ· Ë ÛˆÌ·ÙÈ΋ ·Ó¿Ù˘ÍË (4,5,9,13,14).™Â Û¿ÓȘ ¿ÓÙˆ˜ ÂÚÈÙÒÛÂȘ, Ë ·ÒÏÂÈ· ‚¿-ÚÔ˘˜ ÌÔÚ› Ó· Â›Ó·È ÛËÌ·ÓÙÈ΋, ȉȷ›ÙÂÚ· Û ·È-‰È¿ ÂÊË‚È΋˜ ËÏÈΛ·˜ Î·È Ì¿ÏÈÛÙ· ÎÔÚ›ÙÛÈ·, Ô˘ ÂÈ-ı˘ÌÔ‡Ó ÛÙËÓ ÂÚ›Ô‰Ô ·˘Ù‹ Ù˘ ˙ˆ‹˜ ÙÔ˘˜ Ó· ¯¿-ÛÔ˘Ó ‚¿ÚÔ˜, fiˆ˜ ·ÎÚÈ‚Ò˜ Û˘Ó¤‚Ë Î·È ÛÙÔÓ Ó·ÚfiÂÓ‹ÏÈη ·ÛıÂÓ‹ Ù˘ ÌÂϤÙ˘ Ì·˜ (4,16).

™Â ·ÚÎÂÙ¿ ·È‰È¿ ·Ú·ÙËÚ‹ıËΠ˘ÓËÏ›·, ÊÙˆ-¯‹ Û˘ÁΤÓÙÚˆÛË, ·ÏÏ¿ Î·È ÂÈıÂÙÈ΋ Û˘ÌÂÚÈÊÔÚ¿,Ù· ÔÔ›· fï˜ ˘Ô¯ÒÚËÛ·Ó Ì ÌÈÎÚ‹ Ì›ˆÛË Ù˘

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112

‰fiÛ˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘. ∂Í·›ÚÂÛË ·ÔÙ¤ÏÂÛ·Ó 3·ÛıÂÓ›˜ Ì ¤ÓÙÔÓ˜ ·ÚÂÓ¤ÚÁÂȘ ·fi ÙÔ ∫¡™(ÂÈıÂÙÈÎfiÙËÙ· Î·È Î·Ù·ÛÙÔÏ‹), ÛÙÔ˘˜ ÔÔ›Ô˘˜ ‰ÈÂ-ÎfiË ÙÔ Ê¿ÚÌ·ÎÔ, ·ÊÔ‡ ·Ô‰Â›¯ıËΠfiÙÈ ‹Ù·Ó ηȷӷÔÙÂÏÂÛÌ·ÙÈÎfi ÛÙË Ú‡ıÌÈÛË ÙˆÓ ÎÚ›ÛˆÓ. ™Â¿ÏϘ ‰ÈϤ˜-Ù˘ÊϤ˜, ÂÏÂÁ¯fiÌÂÓ˜ Ì placebo ÌÂ-ϤÙ˜, Û ·ÛıÂÓ›˜ Ô˘ ıÂڷ‡ÔÓÙ·Ó Ì ÙÔÈÚ·-Ì¿ÙË, ÔÈ ·ÚÂÓ¤ÚÁÂȘ ·fi ÙÔ ∫¡™, fiˆ˜ Ë Û˘Ó·È-ÛıËÌ·ÙÈ΋ ·ÛÙ¿ıÂÈ·, Ë ˘ÓËÏ›·, ÔÈ ‰˘ÛÎÔϛ˜ Û˘-ÁΤÓÙÚˆÛ˘, ÚÔÛÔ¯‹˜ Î·È ÌÓ‹Ì˘ Î·È Ë ÎfiˆÛË,·Ú·ÙËÚÔ‡ÓÙ·Ó Ôχ ÈÔ Û˘¯Ó¿ Û˘ÁÎÚÈÙÈο Ì·ÛıÂÓ›˜ Û ıÂڷ›· Ì placebo (4,9). ∞ÓÙ›ıÂÙ·,ÛÙȘ ›‰È˜ ÌÂϤÙ˜, Ë ÂÈıÂÙÈ΋ Û˘ÌÂÚÈÊÔÚ¿ ·-Ú·ÙËÚ‹ıËÎÂ, ÛÙÔ ›‰ÈÔ ÂÚ›Ô˘ ÔÛÔÛÙfi, ÛÙÔ˘˜·ÛıÂÓ›˜ Û ıÂڷ›· Ì placebo (7%) Î·È ÛÙÔ˘˜·ÛıÂÓ›˜ Û ıÂڷ›· Ì ÙÔÈÚ·Ì¿ÙË (10%) (4). °Â-ÓÈο, ¿ÓÙˆ˜, ÔÈ ÚÔ·Ó·ÊÂÚı›Û˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘∫¡™, Ô˘ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È Î·È Î·Ù¿ ÙË ¯ÔÚ‹-ÁËÛË ·ÚÎÂÙÒÓ ¿ÏÏˆÓ ·ÓÙÈÂÈÏËÙÈÎÒÓ Ê·Ú̿ΈÓ(2-3,11), Â›Ó·È ÔÈ ÈÔ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÌÂÓ˜ ‰È·Ù·-Ú·¯¤˜ ηٿ ÙË ¯ÔÚ‹ÁËÛË Ù˘ ÙÔÈÚ·Ì¿Ù˘(5,11,13,14,16), ·ÏÏ¿ Ê·›ÓÂÙ·È Ó· ˘Ô¯ˆÚÔ‡Ó Â›ÙÂÌ ÙË Û˘Ó¤¯ÈÛË Ù˘ ıÂڷ›·˜, ›Ù Ì ÙËÓ ÂÏ¿ÙÙˆ-ÛË Ù˘ ¯ÔÚËÁÔ‡ÌÂÓ˘ ‰fiÛ˘. ∂ÈÚfiÛıÂÙ·, ÎÚ›ÛÈ-ÌË ÛÙËÓ Î·Ù‡ı˘ÓÛË ·˘Ù‹ Â›Ó·È Ë ·ÚÁ‹ ÙÈÙÏÔÔ›Ë-ÛË ÙˆÓ ‰fiÛÂˆÓ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ (·‡ÍËÛË 1 mg/kg/24h ·Ó¿ 2 ‚‰ÔÌ¿‰Â˜), Ô˘ ·ÊÂÓfi˜ ‚ÔËı¿ÂÈ ÛÙÔ Ó·ÂÌÊ·Ó›˙ÔÓÙ·È ÏÈÁfiÙÂÚ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ,·ÊÂÙ¤ÚÔ˘ Û˘Ì‚¿ÏÏÂÈ Î·È ÛÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ÎÚ›ÛˆÓ,Ì ÙË ÌÈÎÚfiÙÂÚË ‰˘Ó·Ù‹ ‰fiÛË Ê·ÚÌ¿ÎÔ˘ (5,11,17).

°ÂÓÈο, ¿ÓÙˆ˜, Ë ÙÔÈÚ·Ì¿ÙË Ê·›ÓÂÙ·È Ó· ›ӷȷÛʷϤ˜ Ê¿ÚÌ·ÎÔ, ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fiÙËÓ ¤ÏÏÂÈ„Ë ÛËÌ·ÓÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÔ‚·ÚÒÓ ‹ ·ÂÈ-ÏËÙÈÎÒÓ ÁÈ· ÙË ˙ˆ‹ ·ÚÂÓÂÚÁÂÈÒÓ (11).

™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÙÔÈÚ·Ì¿ÙË Ê¿ÓËΠӷ ‚ÂÏ-ÙÈÒÓÂÈ ÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ÎÚ›ÛÂˆÓ Û ‰È¿ÊÔÚ· ÂÈÏË-ÙÈο Û‡Ó‰ÚÔÌ· ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ (·ÓıÂÎÙÈο Û¿ÏÏ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η), ¯ÔÚËÁÔ˘Ì¤ÓË Û·ÓÛ˘ÌÏËڈ̷ÙÈ΋ ·ÁˆÁ‹ Ì·˙› Ì ¿ÏÏ· ÎÏ·ÛÈο ηÈÓÂfiÙÂÚ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η. ¶·Ú·ÙËÚ‹ıËηÓÙ·fiÎÚÈÛË Û ÔÛÔÛÙfi ≥50%, ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ̤ÚÔ˜ ÙˆÓ ·È‰ÈÒÓ (64,7%) Î·È È‰È·›ÙÂÚ· ÛÙ· ·È-‰È¿ Ì ÔÔÈ·Û‰‹ÔÙ ÌÔÚÊ‹˜ Î·È ·ÈÙÈÔÏÔÁ›·˜ÂÛÙȷ΋ ÂÈÏË„›·, ÂÓÒ Ôχ ÈηÓÔÔÈËÙÈ΋ ıˆÚ›-Ù·È Î·È Ë ·ÓÙ·fiÎÚÈÛË Ô˘ ¤‰ÂÈÍ·Ó ÛÙÔ Ê¿ÚÌ·ÎÔ ÔÈ·ÛıÂÓ›˜ Ì ۇӉÚÔÌÔ Lennox-Gastaut. ∆Ô Ê¿ÚÌ·-ÎÔ ‹Ù·Ó ÁÂÓÈο ηÏÒ˜ ·ÓÂÎÙfi ·fi ÙÔ Û‡ÓÔÏÔ ÙˆÓ·ÛıÂÓÒÓ Î·È ÔÈ ·ÚÂÓ¤ÚÁÂȘ Ô˘ ·ÚÔ˘ÛÈ¿ÛÙËηÓÛÙÔ 58,8% ‹Ù·Ó ˆ˜ › ÙÔ Ï›ÛÙÔÓ ‹È˜ Î·È ·-ÚÔ‰ÈΤ˜, ÂÓÒ ÌfiÓÔ 4 ·ÛıÂÓ›˜ (23,5%) ‰È¤ÎÔ„·ÓÙËÓ ·ÁˆÁ‹. £· Ú¤ÂÈ, fï˜, Ó· ÙÔÓÈÛÙ› fiÙÈ ÔÈ·ÒÙÂÚ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Â›Ó·È ·ÎfiÌË¿ÁÓˆÛÙ˜.

µÈ‚ÏÈÔÁÚ·Ê›·1. Thomas P, Arzimanoglou A. ∂ÈÏË„›Â˜. 2Ë ÂΉ. ·Ó¿‰. ÛÙ·

ÂÏÏËÓÈο, ∂. ∂Ή. ¶·ÚÈÛÈ¿ÓÔ˘ ∞.∂.; 2002. ÛÂÏ. 254.2. Marson AG, Kadir ZA, Chadwick DW. New antiepileptic

drugs: a systematic review of their efficacy and tolerability.BMJ 1996;313:1169-1174.

3. Ferrie CD, Livingston JH. The new anti-epileptic drugs: areview. Eur J Pediatr Neurol 1997;1:139-147.

4. Elterman RD, Glauser TA, Wyllie E, Reife R, Wu SC, PledgerG. A double-blind, randomized trial of topiramate asadjunctive therapy for partial-onset seizures in children.¡eurology 1999;52:1338-1344.

5. Uldall P, Buchholt JM. Clinical experiences with topiramatein children with intractable epilepsy. Eur J Pediatr Neurol1999;3:105-111.

6. Wheless JW. Use of topiramate in childhood generalizedseizure disorders. J Child Neurol 2000;15 (1 suppl):S7-13.

7. Glauser TA, Clark PO, Strawsburg R. A pilot study oftopiramate in the treatment of infantile spasms. Epilepsia1998;39:1324-1328.

8. Glauser TA, Levisohn PM, Ritter F, Sachdeo RC.Topiramate in Lennox-Gastaut syndome: open-labeltreatment of patients completing a randomized controlledtrial. Topiramate YL Study Group. Epilepsia 2000;41 (1Suppl):S86-90.

9. Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, PledgerG. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group. Neurology1999;52:1882-1887.

10. Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. Anoverview of the preclinical aspects of topiramate:pharmacology, pharmacokinetics, and mechanism ofaction. Epilepsia 2000;41 (1 Suppl):S3-9.

11. Bourgeois BF. Pharmacokinetics and pharmacodynamicsof topiramate. J Child Neurol 2000;15 (1 suppl):S27-30.

12. Commission on Classification and Terminology of theInternational League Against Epilepsy. Proposal for revisedclassification of epilepsies and epileptic syndromes.Epilepsia 1989;30:389-399.

13. ƒ›˙Ô˘ Ã, ∫fiÙÛ·Ï˘ Ã, ¶·Ú·ÛÎÂ˘Ô˘Ï¿ÎÔ˜ ∂, ª·˙›ÁÔ˘ ∂,°È·ÓÓ¤ÏË ª, ¶··‚·ÛÈÏ›Ԣ ∞. ∆ÔÈÚ·Ì¿ÙË ˆ˜ ÚfiÛıÂÙË·ÁˆÁ‹ Û ·ÓıÂÎÙÈΤ˜ ÂÈÏË„›Â˜ ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ - ÂÌÂÈ-Ú›· ÂÓfi˜ ¤ÙÔ˘˜. 16Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ∂ÏÏ‹ÓˆÓ ¡Â˘ÚÔÏfi-ÁˆÓ. £ÂÛÛ·ÏÔÓ›ÎË; 1999, π·ÓÔ˘¿ÚÈÔ˜ 20-23, ∆ÔÌ. ÂÚ›Ï: 9-15.

14. Yeung S, Ferrie CD, Murdoch-Eaton DG, Livingston JH.Topiramate for drug-resistant epilepsies. Eur J PediatrNeurol 2000;4:31-33.

15. Cross JH. Epilepsy: topiramate as monotherapy in children.Eur J Pediatr Neurol 2001;5:∞73.

16. Levisohn PM. Safety and tolerability of topiramate inchildren. J Child Neurol 2000;15 (1 Suppl):S22-26.

17. Shorvon SD. Safety of topiramate: adverse events andrelationships to dosing. Epilepsia 1996;37 (2 Suppl):S18-22.

HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 13-09-2002 HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 24-01-2003

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ªÂÚfiË ∆˙Ô‡ÊË ∆Ô̤·˜ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡ π·ÙÚÈ΋ ™¯ÔÏ‹, ¶·Ó/ÌÈÔ πˆ·ÓÓ›ÓˆÓ∆.£. 1186, ∆.∫. 451 10, πˆ¿ÓÓÈÓ·

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113

ªÂȈ̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ ÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ Ê·ÈÓ˘ÏÎÂÙÔÓÔ˘ÚÈÎÒÓ ·ÛıÂÓÒÓ ∫. ∂. ™Ô‡ÏË1, °. ∞. ∫·Ú›Î·˜2, π. ∆˙·ÌÔ˘Ú¿ÓË1, ∂. ªÈ¯ÂϷοÎË1, ™. ∆۷ΛÚ˘3

Reduced acetylcholinesterase activity of erythrocyte membranes from patients with phenylketonuria ∫. ∏. Schulpis1, G. A. Karikas2, I. Tjamouranis1, H. Michelakakis1, S. Tsakiris3

∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞ ORIGINAL ARTICLE

1 πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·

2 ªÔÓ¿‰· ∂Ó‰ÔÊϤ‚ÈˆÓ ¢È·Ï˘Ì¿ÙˆÓ Î·È º·ÚÌ·ÎÔÎÈÓËÙÈ΋˜,¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·

3 ∂ÚÁ·ÛÙ‹ÚÈÔ ¶ÂÈÚ·Ì·ÙÈ΋˜ º˘ÛÈÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ

1 Institute of Child Health, “Agia Sophia” Children’s Hospital, Athens

2 Division of Intravenous Solutions and Pharmacokinetics,“Agia Sophia” Children’s Hospital, Athens

3 Laboratory of Experimental Physiology, University of Athens Medical School

�¶ÂÚ›ÏË„Ë: ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÂÚÁ·Û›·˜‹Ù·Ó: ·) Ë Ì¤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ·ÎÂ-Ù˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ (∞Ã) ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ÌÂÌ‚Ú¿Ó˜ ·ÛıÂÓÒÓ Ì ÎÏ·ÛÈ΋ Ê·ÈÓ˘ÏÎÂÙÔÓÔ˘Ú›·(PKU) Î·È Ì·ÚÙ‡ÚˆÓ Î·È Ë Û˘Û¯¤ÙÈÛ‹ Ù˘ Ì ٷ ›-‰· ÙˆÓ ·ÌÈÓÔͤˆÓ Ê·ÈÓ˘Ï·Ï·Ó›ÓË (º·È), Ù˘ÚÔÛ›-ÓË (∆˘Ú) Î·È ·Ï·Ó›ÓË (∞Ï·) ÛÙÔ Ï¿ÛÌ· ÙÔ˘˜, fiˆ˜Â›Û˘ Î·È Ù˘ ÓÙÔ·Ì›Ó˘ (¡ÙÔ), ‚) Ë ÌÂϤÙË ÙˆÓin vitro ÂȉڿÛÂˆÓ Ù˘ º·È, ∞Ï· Î·È Ù˘ º·È+∞Ï·ÛÙË ‰Ú·ÛÙÈÎfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘. ∏ ‰Ú·ÛÙÈÎfiÙËÙ·Ù˘ ∞à ÚÔÛ‰ÈÔÚ›ÛÙËΠʈÙÔÌÂÙÚÈο ÛÙȘ ÂÚ˘ıÚÔ-΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ, ÔÈ ÔÔ›ÔÈ·ÎÔÏÔ˘ıÔ‡Û·Ó ÛˆÛÙ¿ ÙË ‰›·ÈÙ¿ ÙÔ˘˜ (ÔÌ¿‰· ∞,¡=12), Û 11 PKU ·ÛıÂÓ›˜ Ì ¯·Ï·Ú‹ ‰›·ÈÙ·(ÔÌ¿‰· µ) Î·È Û 23 ˘ÁÈ›˜ ·ÛıÂÓ›˜ ·ÓÙ›ÛÙÔȯ˘ËÏÈΛ·˜. ∆· ·ÌÈÓÔͤ· ÚÔÛ‰ÈÔÚ›ÛÙËÎ·Ó Ì ·˘ÙfiÌ·-ÙÔ ·Ó·Ï˘Ù‹ ·ÌÈÓÔͤˆÓ Î·È Ë ¡ÙÔ Ì HPLC. In vitro,AÏ· (1,8 mM) ‹ º·È (1,8 mM) ‹ Û˘Á¯ÚfiÓˆ˜ º·È (1,8mM)+∞Ï· (1,8 mM) ÚÔÛÙ¤ıËÎ·Ó ÛÙÔ Ì›ÁÌ· ˆ-¿Ûˆ˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ, ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ ∞,ÂÓÒ ÌfiÓÔ AÏ· ÚÔÛÙ¤ıËΠÛÙÔ Ì›ÁÌ· Ù˘ ÔÌ¿‰·˜µ. ∏ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à (1,19±0,05 ¢OD/min xmg protein), ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ Ù˘ ∆˘Ú (0,83±0,30mg/dl) Î·È Ù˘ ¡ÙÔ (56±18 Ìmol/l) ‹Ù·Ó ÛËÌ·ÓÙÈοÌÂȈ̤Ó˜ (60%, p<0,001) ÛÙËÓ ÔÌ¿‰· µ Û˘ÁÎÚÈ-ÓfiÌÂÓ˜ Ì ÙËÓ ÔÌ¿‰· ∞ (3,01±0,18 ¢OD/min x mgprotein, 2,09±0,7 mg/dl, 137±29 Ìmol/l) Î·È ÌÂÙÔ˘˜ Ì¿ÚÙ˘Ú˜ (3,13±0,16 ¢OD/min x mg protein,2,13±0,80 mg/dl, 142±22 Ìmol/l, p<0,001). ∏ º·ÈÛ˘Û¯ÂÙÈ˙fiÙ·Ó ·ÚÓËÙÈο Ì ÙËÓ ∞Ã Î·È ıÂÙÈο Ì ÙËÓ∆˘Ú Î·È ÙË ¡ÙÔ. ∏ ∞Ï· ·ÓÙ¤ÛÙÚ„ ÙËÓ ·ÚÓËÙÈ΋

�Abstract: The aims of this study were: a) toevaluate acetylcholinesterase (AChE) activity inerythrocyte membranes from phenylketonuric(PKU) patients and controls, b) to correlate AChEactivity with plasma levels of phenylalanine (Phe),tyrosine (Tyr), alanine (Ala) and dopamine (DA),and c) to determine the in vitro effects of Phe, Alaand Phe plus Ala on AChE activities. AChE activitywas determined spectrophotometrically inerythrocyte membranes from 12 PKU childrenadhering to their diet (group A), from 11 PKUchildren on a “loose diet” (group B) and from 23controls. Amino acids were evaluated with ananalyser and DA by HPLC. Ala (1.8 mM) and/or Phe(1.8 mM) were added to the enzyme incubationmedium from the controls, and Ala alone wasadded to that from group B. AChE activity(1.19±0.05 ¢OD/min x mg protein), Tyr (0.83±0.30mg/dl) and DA (56±18 Ìmol/l) were lower by about60% in group B than in group A (3.01±0.18¢OD/min x mg protein, 2.09±0.70 mg/dl, 137±29Ìmol/l, respectively, p<0.001) and in the controlgroup (3.13±0.16 ¢OD/min x mg protein,2.13±0.80 mg/dl, 142±22 Ìmol/l, respectively,p<0.001). Phe was correlated negatively with AChEactivity and positively with Tyr and DA. In the controlgroup, Ala reversed the inhibition of AChE by Phe,whereas no effect was observed on the enzymeactivity in the PKU patients. In conclusion, a) thedetermination of AChE in erythrocyte membranesfrom PKU patients may be a peripheral marker for

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∂ÈÛ·ÁˆÁ‹∏ Ê·ÈÓ˘ÏÎÂÙÔÓÔ˘Ú›· (PKU) Â›Ó·È ¤Ó· ÌÂÙ·‚ÔÏÈ-

Îfi ÓfiÛËÌ· Ô˘ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ˘ÔÏÂÈfiÌÂÓÔۈ̷ÙÈÎfi ÁfiÓÔ ÌÂ Û˘¯ÓfiÙËÙ· 1:15000 ÁÂÓÓ‹ÛÂȘ. ∏‰È·Ù·Ú·¯‹ ·˘Ù‹ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·ÌÈÓÔͤԘʷÈÓ˘Ï·Ï·Ó›ÓË (º·È) ÔÊ›ÏÂÙ·È ÛÙËÓ ·Ó¿ÚÎÂÈ·ÙÔ˘ Ë·ÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ ˘‰ÚÔÍ˘Ï¿ÛË Ù˘ º·È, Ì·ÔÙ¤ÏÂÛÌ· ÙËÓ ·˘ÍË̤ÓË Û˘ÁΤÓÙÚˆÛË ÙÔ˘ ·ÌÈ-ÓÔͤԘ Û fiÏ· Ù· ‚ÈÔÏÔÁÈο ˘ÁÚ¿. OÈ PKU ·ÛıÂÓ›˜¯ˆÚ›˜ ıÂڷ›· ÂÌÊ·Ó›˙Ô˘Ó „˘¯ÔÎÈÓËÙÈ΋ ηı˘ÛÙ¤-ÚËÛË, ‰È·Ù·Ú·¯¤˜ Û˘ÌÂÚÈÊÔÚ¿˜, Û·ÛÌÔ‡˜, ¤Î-˙ÂÌ· Î.Ï. (1). ∆· ˘„ËÏ¿ ›‰· Ù˘ º·È (7-20mg/dl ‹ 0,4-1,2 mª) Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ˘˜ ·ÛıÂ-Ó›˜ Â›Ó·È È‰È·›ÙÂÚ· ‚Ï·ÙÈο ηٿ ÙÔÓ ÚÒÙÔ ¯Úfi-ÓÔ ˙ˆ‹˜. OÈ ‚Ï¿‚˜ ·˘Ù¤˜ ÚÔÏ·Ì‚¿ÓÔÓÙ·È Ì ÙËÛˆÛÙ‹ ‰È·ÈÙËÙÈ΋ Ú‡ıÌÈÛË (2-4). ¢˘ÛÙ˘¯Ò˜, ÔÏÏÔ›·fi ÙÔ˘˜ PKU ·ÛıÂÓ›˜ ‰ÂÓ ·ÎÔÏÔ˘ıÔ‡Ó ·˘ÛÙËÚ¿ÙËÓ ÂȉÈ΋ ‰›·ÈÙ¿ ÙÔ˘˜ (¯·Ï·Ú‹ ‰›·ÈÙ·), Ì ·ÔÙ¤-ÏÂÛÌ· ÙËÓ ·˘ÍË̤ÓË Û˘ÁΤÓÙÚˆÛË Ù˘ º·È ÛÙÔ ·›-Ì· ÙÔ˘˜ Î·È ÙË ¯·ÌËÏ‹ Ù˘ÚÔÛ›ÓË (∆˘Ú), Ë ÔÔ›· ›-Ó·È ÚÔ‰ÚÔÌÈ΋ Ô˘Û›· ÙÔ˘ Ó¢Úԉȷ‚È‚·ÛÙ‹ ÓÙÔ·-Ì›ÓË (¡ÙÔ) (1,5). ™˘ÓÂÒ˜, Ù· ·Ú·ÙËÚÔ‡ÌÂÓ· ¯·-ÌËÏ¿ ›‰· Ù˘ ∆˘Ú ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÌÂȈ̤ÓË ·Ú·ÁˆÁ‹ ·‰ÚÂÓÂÚÁÈÎÒÓ ·ÌÈÓÒÓ fiˆ˜ Ë¡ÙÔ, Ë ÔÔ›· ÌÂÈÒÓÂÙ·È ÛËÌ·ÓÙÈο (5,6). ∂›Û˘, Ù·˘„ËÏ¿ ›‰· Ù˘ º·È ‚Ú¤ıËΠfiÙÈ ÂȉÚÔ‡Ó Î·ÈÛ ¿ÏÏÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ó¢ÚÈ΋˜ ‰ÈÂÁÂÚÛÈÌfiÙËÙ·˜(1,3), ·ÍÔÓÈ΋˜ Û‡Ó‰ÂÛ˘, Û˘Ó·ÙÈ΋˜ ·ÎÔÏÔ˘ı›·˜Î.Ï. (7).

™Â ÚÔËÁÔ‡ÌÂÓ˜ in vitro ÌÂϤÙ˜, ÔÈ ‰Ú·ÛÙÈÎfi-ÙËÙ˜ Ù˘ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ (∞Ã) Û ÔÌÔÁÂÓÔ-Ô›ËÌ· ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡, ·ÏÏ¿ Î·È ÙÔ˘ ηı·-ÚÔ‡ ÂÓ˙‡ÌÔ˘ Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi ÙÔ ¯¤ÏÈ E.electricus, ‚Ú¤ıËΠfiÙÈ ÌÂÈÒÓÔÓÙ·È Î·Ù¿ 20% fiÙ·Óˆ·ÛıÔ‡Ó ÛÂ Û˘ÁÎÂÓÙÚÒÛÂȘ º·È 7-20 mg/dl ‹0,4-1,2 mª, Û‡ÓËı˜ ‡ÚËÌ· ÛÙÔ ·›Ì· PKU ·ÛıÂ-ÓÒÓ Ì ¯·Ï·Ú‹ ‰›·ÈÙ· ‹ ¯ˆÚ›˜ ‰È·ÈÙËÙÈ΋ ·ÁˆÁ‹.∂›Û˘, Û ¿ÏÏË ÂÚÁ·Û›· (9), Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘∞à ÛÙÔ ‰È¿ÊÚ·ÁÌ· ÔÓÙÈÎÔ‡ Ì ·ÚÔ˘Û›· ˘„ËÏÔ‡

ÂȤ‰Ô˘ º·È, ‚Ú¤ıËΠÌÂȈ̤ÓË Î·Ù¿ 20%. ™Â Ì›·ÚfiÛÊ·ÙË in vitro ÌÂϤÙË (10) ·Ú·ÙËÚ‹ıËΠfiÙÈ ÙÔ·ÌÈÓÔ͇ L-·Ï·Ó›ÓË (∞Ï·) ıÂÙÈÎÔÔÈ› ‹ ÚÔÛٷهÂÈÙËÓ ∞à ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡ ‹ ηı·ÚÔ‡ ÂÓ˙‡ÌÔ˘ ·fiÙËÓ ·Ó·ÛÙ·ÏÙÈ΋ ‰Ú¿ÛË Ù˘ º·È. ∞ÎfiÌË, ·Ó·Ê¤ÚÂÙ·ÈfiÙÈ Ë ∞à ¤ÌÌÂÛ· ÂËÚ¿˙ÂÙ·È ·fi ÙË ¡ÙÔ (11), ËÔÔ›· ¤¯ÂÈ ‚ÚÂı› ÌÂȈ̤ÓË ÛÙÔÓ ÂÁΤʷÏÔ PKU·ÛıÂÓÒÓ Ì ˘„ËÏ¿ ›‰· º·È ÛÙÔ ·›Ì· ÙÔ˘˜ (12).

∂›Ó·È ÚÔÊ·Ó¤˜ fiÙÈ Ô ·ÓıÚÒÈÓÔ˜ ÂÁΤʷÏÔ˜‰ÂÓ Â›Ó·È ÚÔÛÈÙfi˜ Û ̛· ¿ÌÂÛË ·ÍÈÔÏfiÁËÛË Ù˘‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞Ã. ™˘ÓÂÒ˜, Â›Ó·È ÂӉȷʤÚÔÓÓ· ·Ó¢ÚÂıÔ‡Ó ÂÚÈÊÂÚÈÎÔ› ‰Â›ÎÙ˜, ÔÈ ÔÔ›ÔÈ ı·Â›Ó·È ·ÓÙÈÚÔÛˆÂ˘ÙÈÎÔ› ÙˆÓ ÂȉڿÛÂˆÓ Ù˘ º·ÈÛÙÔ ¤Ó˙˘ÌÔ ÙÔ˘ ∫¡™.

™ÙËÓ ·ÚÔ‡Û· ÂÚÁ·Û›· ÌÂÙÚ‹ıËÎÂ Ë ‰Ú·ÛÙÈÎfi-ÙËÙ· Ù˘ ∞à Û ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ PKU·ÛıÂÓÒÓ Î·È Ì·ÚÙ‡ÚˆÓ ·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜, ¤ÁÈÓÂÛ˘Û¯¤ÙÈÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÙÔ˘ ÂÓ˙‡ÌÔ˘ Ì ٷ›‰· ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∆˘Ú, ∞Ï· Î·È ÙÔ˘ Ó¢-Úԉȷ‚È‚·ÛÙ‹ ¡ÙÔ Î·È ÌÂÏÂÙ‹ıËΠin vitro ÙÔ ·ÔÙ¤-ÏÂÛÌ· Ù˘ ›‰Ú·Û˘ ‰È·ÊfiÚˆÓ Û˘ÁÎÂÓÙÚÒÛˆӺ·È, ∞Ï·, ∞Ï·+º·È ÛÙËÓ ∞à ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓÌÂÌ‚Ú·ÓÒÓ PKU ·ÛıÂÓÒÓ, ·ÏÏ¿ Î·È Ì·ÚÙ‡ÚˆÓ.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ¤Ï·‚·Ó ̤ÚÔ˜ 23 PKU ·ÛıÂÓ›˜, ÔÈ

ÔÔ›ÔÈ ‰È·¯ˆÚ›ÛÙËÎ·Ó Û ‰‡Ô ÔÌ¿‰Â˜. ∏ ÔÌ¿‰· ∞ (N=12) Â-ÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì ̤ÛË ËÏÈΛ· Ù· 6,8±1,2 ¤ÙË, Ì ۯ‰fiÓÊ˘ÛÈÔÏÔÁÈο ›‰· º·È ÛÙÔ ·›Ì· ÙÔ˘˜ (º·È 1,57±0,52 mg/dl‹ 0,10±0,03 mª). ∏ ÔÌ¿‰· µ (¡=11) ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜Ì ̤ÛË ËÏÈΛ· Ù· 7,2±2,0 ¤ÙË, Û ¯·Ï·Ú‹ ‰›·ÈÙ· (º·È28,45±1,5 mg/dl ‹ 1,72±0,09 mª). ∂›ÎÔÛÈ ÙÚÂȘ (¡=23) ˘ÁÈ›˜Ì¿ÚÙ˘Ú˜, ·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜, ›¯·Ó Ê˘ÛÈÔÏÔÁÈο ›‰· º·È(1,45±0,60 mg/dl ‹ 0,09±0,03 mª). ŸÏÔÈ ÔÈ PKU ·ÛıÂÓ›˜ ·-Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È ÛÙÔ πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡.

ªÂ ÙËÓ Â˘Î·ÈÚ›· Ù˘ ÂÙ‹ÛÈ·˜ ·ÍÈÔÏfiÁËÛ˘ ÙˆÓ ·ÛıÂ-ÓÒÓ, Ï‹ÊıËΠ·›Ì· 5,0 ml Û ˷ÚÈÓÈṲ̂ÓË Û‡ÚÈÁÁ·, 3ÒÚ˜ ÌÂÙ¿ ÙËÓ Â›Û΄‹ ÙÔ˘˜, ÒÛÙ ӷ ›¯·Ó ÂÁÎÏÈÌ·ÙÈÛÙ›ÛÙÔ ÂÚÈ‚¿ÏÏÔÓ.

›‰Ú·ÛË Ù˘ º·È ÛÙË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à وÓÌ·ÚÙ‡ÚˆÓ. ∞ÓÙ›ıÂÙ·, Ë ∞Ï· ‰ÂÓ Â›¯Â ηӤӷ ·ÔÙ¤-ÏÂÛÌ· ÛÙËÓ ∞Ã ÙˆÓ PKU ·ÛıÂÓÒÓ. ™˘ÌÂÚ·ÛÌ·ÙÈ-ο, ·) Ë Ì¤ÙÚËÛË ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ-‚Ú¿Ó˜ ·ÛıÂÓÒÓ Ì PKU ı· ÌÔÚÔ‡Û ӷ ıˆÚË-ı› ˆ˜ Ô˘ÛÈ҉˘ ‰Â›ÎÙ˘ Ù˘ ÙÔÍÈÎfiÙËÙ·˜ Ù˘ º·ÈÛÙÔ ∫¡™, ‚) Ù· ˘„ËÏ¿ ›‰· º·È ¤¯Ô˘Ó ˆ˜ ·Ô-Ù¤ÏÂÛÌ· ÙË ÌÂȈ̤ÓË ÛÙ¿ıÌË Ù˘ ¡ÙÔ Î·È ÙÔ˘ ÚÔ-‰ÚÔÌÈÎÔ‡ Ù˘ ·ÌÈÓÔͤԘ ∆˘Ú, fiˆ˜ ›Û˘ ÙËÓ·Ó·ÛÙÔÏ‹ Ù˘ ∞à ÛÙÔ˘˜ PKU ·ÛıÂÓ›˜ Ì Èı·Ó‹·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ·ÎÂÙ˘Ï¯ÔÏ›Ó˘.

§¤ÍÂȘ ÎÏÂȉȿ: Ê·ÈÓ˘Ï·Ï·Ó›ÓË, ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂ-Ú¿ÛË, ÓÙÔ·Ì›ÓË, ·Ï·Ó›ÓË.

the neurotoxic brain effects of Phe, b) the low levelsof DA and its precursor Tyr result from high Phelevels which inhibit AChE in PKU patients, probablycausing higher acetylcholine concentrations.

Key words: phenylalanine, acetylcholinesterase,dopamine, alanine.

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∂ÓÙfi˜ 2 ˆÚÒÓ ·fi ÙËÓ ·ÈÌÔÏË„›·, ÙÔ ·›Ì· Ê˘ÁÔÎÂ-ÓÙÚ‹ıËΠ(2000 g ÁÈ· 30 min ÛÙÔ˘˜ 4ÔC). ∆o ›˙ËÌ· χıË-Π3-4 ÊÔÚ¤˜ Ì ڢıÌÈÛÙÈÎfi ‰È¿Ï˘Ì· (250 mª tris(hydroxymethyl) aminomethane - HCl (tris HCl), pH 7,4, 140mM NaCl, 1 mM MgCl2, 10 mM ÁÏ˘Îfi˙Ë) ÌÂÙ¿ ·fi 3 Ê˘-ÁÔÎÂÓÙÚ‹ÛÂȘ. ™ÙÔ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎfi ›˙ËÌ· ÚÔÛÙ¤ıËΠ1ml ÙÔ˘ ›‰ÈÔ˘ Ú˘ıÌÈÛÙÈÎÔ‡ ‰È·Ï‡Ì·ÙÔ˜ Î·È Ê˘Ï¿¯ÙËΠÛÙÔ˘˜4ÔC ÁÈ· 24 ÒÚ˜ ÚÈÓ ÙËÓ ÚÔ·Ú·Û΢‹ ÙˆÓ ÂÚ˘ıÚÔ΢Ù-Ù·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ Ì ÙȘ ÌÂıfi‰Ô˘˜ Ô˘ ÂÚÈÁÚ¿ÊÔÓÙ·È·fi ÙÔ˘˜ Galbraith Î·È Watts (13) Î·È ∫amber Î·È Û˘Ó (14).™ÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÌÂÙÚ‹ıËÎÂ Ë ÚˆÙ½ÓË,fiˆ˜ ÂÚÈÁÚ¿ÊÂÙ·È ·fi ÙÔ˘˜ Lowry Î·È Û˘Ó (15) Î·È Ê˘-Ï¿¯ÙËÎ·Ó ÁÈ· 2 ‚‰ÔÌ¿‰Â˜ ÛÙÔ˘˜ -40oC. ∆· ˘ÔÏ›ÌÌ·Ù·Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÛÙȘ ÌÂÌ‚Ú¿Ó˜ ÌÂÙÚ‹ıËÎ·Ó Ì kit (527-A Sigma Chemical Co, St. Louis, USA) Î·È Ë ÙÈÌ‹ Ù˘ ·Ê·È-Ú¤ıËΠ·fi ÙËÓ ÔÏÈ΋ ÚˆÙ½ÓË.

∏ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ-‚Ú¿Ó˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ ÌÂÙÚ‹ıËΠÚÈÓ ‹ ÌÂÙ¿ ÙËÓ in vitroÚÔÂÒ·ÛË ÁÈ· 1 ÒÚ· Ì º·È 30 mg/dl (=1,8 mª) ‹ 1,8mª ∞Ï· ‹ º·È+∞Ï·. ∆Ô ¤Ó˙˘ÌÔ Ô˘ ÚÔÂÚ¯fiÙ·Ó ·fi ÙȘÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ Ì ¯·Ï·Ú‹ ‰›·ÈÙ·, ÌÂÙÚ‹ıËΠÌÂÙËÓ ·ÚÔ˘Û›· ‹ ÙËÓ ·Ô˘Û›· 1,8 mª ∞Ï·.

∏ ̤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞à ÛÙȘ ÂÚ˘ıÚÔ΢Ù-Ù·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ Î·È Ì·ÚÙ‡ÚˆÓ Ú·ÁÌ·-ÙÔÔÈ‹ıËΠ̠ÙË Ì¤ıÔ‰Ô Ellman Î·È Û˘Ó (16), fiˆ˜ ÙÚÔ-ÔÔÈ‹ıËΠ·fi ÙÔÓ Tsakiris (17).

OÈ ÔÛÔÙÈÎÔ› ÚÔÛ‰ÈÔÚÈÛÌÔ› ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∆˘Ú ηÈ∞Ï· ¤ÁÈÓ·Ó Ì ·˘ÙfiÌ·ÙÔ ·Ó·Ï˘Ù‹ ·ÌÈÓÔͤˆÓ (Biotronic LC5001), ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙË ÓÔÚÏ¢ΛÓË ˆ˜ standard. ∆Ô CV(%) ÁÈ· ÙË º·È, ÙËÓ ∆˘Ú Î·È ÙËÓ ∞Ï· ‹Ù·Ó 3,1, 2,9 Î·È 2,8,·ÓÙ›ÛÙÔȯ·. ∏ ¡ÙÔ ÌÂÙÚ‹ıËΠ̠∏PLC ÛÙÔ Ï¿ÛÌ· (11) ÌÂCV (%) 3,4.

∆· ·ÔÙÂϤÛÌ·Ù· ·Ó·Ï‡ıËÎ·Ó Ì ANOVA Î·È t-test. OÈ‚·ıÌÔ› Û˘Û¯¤ÙÈÛ˘ ˘ÔÏÔÁ›ÛÙËÎ·Ó Ì ÙÔ Spearman test ÛÂ∏/À, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙÔ SPSS 10.0 ÛÙ·ÙÈÛÙÈÎfi ·Î¤ÙÔ.

∞ÔÙÂϤÛÌ·Ù·Ÿˆ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔÓ ¶›Ó·Î· 1, ÔÈ Û˘ÁÎÂ-

ÓÙÚÒÛÂȘ Ù˘ ∆˘Ú, Ù˘ ¡ÙÔ Î·È Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘∞à ÛÙËÓ ÔÌ¿‰· µ ÙˆÓ PKU ·ÛıÂÓÒÓ ‹Ù·Ó ÛÙ·ÙÈÛÙÈ-

ο ÛËÌ·ÓÙÈο ¯·ÌËÏfiÙÂÚ˜ (ÂÚ›Ô˘ 60%,p<0,001), Û˘ÁÎÚÈÓfiÌÂÓ˜ Ì ÂΛӘ ÙˆÓ Ì·ÚÙ‡-ÚˆÓ, fiˆ˜ ›Û˘ Î·È Ù˘ ÔÌ¿‰·˜ ∞. Ÿˆ˜ ‹Ù·Ó·Ó·ÌÂÓfiÌÂÓÔ, Ù· ›‰· º·È ‹Ù·Ó ÛËÌ·ÓÙÈο ·˘-ÍË̤ӷ ÛÙËÓ ÔÌ¿‰· µ, ÂÓÒ Ë ∞Ï· ‰ÂÓ ·ÚÔ˘Û›·ÛÂοÔÈ· ‰È·ÊÔÚ¿ Û fiϘ ÙȘ ÔÌ¿‰Â˜ ÌÂϤÙ˘.

™ÙÔÓ ¶›Ó·Î· 2 Ê·›ÓÂÙ·È fiÙÈ Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘∞Ã Û˘Û¯ÂÙÈ˙fiÙ·Ó ¿ÌÂÛ· Ì ٷ ›‰· Ù˘ ¡ÙÔ Î·ÈÙÔ˘ ÚÔ‰ÚfiÌÔ˘ ·ÌÈÓÔͤԘ Ù˘ ∆˘Ú, ·ÏÏ¿ ‰ÂÓ Û˘-Û¯ÂÙÈ˙fiÙ·Ó Ì ÙËÓ ∞Ï·. ∞ÓÙ›ıÂÙ·, Ë ‰Ú·ÛÙÈÎfiÙËÙ·ÙÔ˘ ÂÓ˙‡ÌÔ˘ ¤‰ÂÈÍ ÈÛ¯˘Ú‹ ·ÚÓËÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂÙ· ›‰· Ù˘ º·È.

™ÙÔÓ ¶›Ó·Î· 3 ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· in vitro ·Ô-ÙÂϤÛÌ·Ù· Ù˘ ÚÔÂÒ·Û˘ ÙˆÓ ·ÌÈÓÔͤˆÓ º·È,∞Ï· ‹ ∞Ï·+º·È ÛÙÔ ÌÂÌ‚Ú·ÓÈÎfi ¤Ó˙˘ÌÔ ∞à ÛÙȘÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ.ŸÙ·Ó ÚÔÛÙ¤ıËΠ∞Ï· (1,8 mM) ÛÙÔ Ì›ÁÌ· Ô˘ÂÌÂÚÈ›¯Â ÙÔ ·Ó·ÛÙ·Ï̤ÓÔ ¤Ó˙˘ÌÔ ·fi ÙË º·È ÛÙȘÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ, ˉڷÛÙÈÎfiÙËÙ· ÙÔ˘ ÂÓ˙‡ÌÔ˘ ·ӋÏı ÛÙËÓ ·Ú¯È΋ÙÈÌ‹. ∏ º·È ÛÂ Û˘ÁΤÓÙÚˆÛË 30 mg/dl (1,8 mM),fiˆ˜ ÌÂÙÚ‹ıËΠÛÙÔ Ï¿ÛÌ· ÙˆÓ ·ÛıÂÓÒÓ Ù˘ÔÌ¿‰·˜ µ, ·Ó¤ÛÙÂÈÏ ÙËÓ ∞à ηٿ 35% (p<0,001).∏ ›‰È· Û˘ÁΤÓÙÚˆÛË Ù˘ ∞Ï·, fï˜, ‰ÂÓ Â¤ÊÂÚÂÛ ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË Î·Ó¤Ó· ·ÔÙ¤ÏÂÛÌ·(p>0,05).

™˘˙‹ÙËÛË ∏ ›ÛÔ‰Ô˜ ÙˆÓ ·ÌÈÓÔͤˆÓ ‰È·Ì¤ÛÔ˘ ÙÔ˘ ·ÈÌ·ÙÔ-

ÂÁÎÂÊ·ÏÈÎÔ‡ ÊÚ·ÁÌÔ‡ ÂËÚ¿˙ÂÙ·È ·fi ÔÏÏÔ‡˜·Ú¿ÁÔÓÙ˜. π‰È·›ÙÂÚ·, Ë ÌÂÙ·ÊÔÚ¿ Ù˘ º·È Î·È Ù˘∆˘Ú Á›ÓÂÙ·È ÛÙÔ ›‰ÈÔ Û‡ÛÙËÌ· ÌÂÙ·ÊÔÚ¿˜ (5). ª›·ÌÂÁ¿ÏË ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÂÓfi˜ ·ÌÈÓÔͤ-Ô˜, fiˆ˜ Ù˘ º·È ÛÙËÓ ÔÌ¿‰· µ ÙˆÓ ·ÛıÂÓÒÓ, ·-ÚÂÌÔ‰›˙ÂÈ ¿ÏÏ· ·ÌÈÓÔͤ·, fiˆ˜ ÙËÓ ∆˘Ú, Ó· ÂÈ-Û¤ÏıÔ˘Ó ÛÙÔÓ ÂÁΤʷÏÔ (19). ªÂ ÙÔÓ ÙÚfiÔ ·˘Ùfi,Ù· ˘„ËÏ¿ ›‰· º·È ·ÚÂÌ‚·›ÓÔ˘Ó ÛÙË ÌÂÙ·ÙÚÔ-‹ Ù˘ ∆˘Ú ÛÙÔÓ Ó¢Úԉȷ‚È‚·ÛÙ‹ ¡ÙÔ, Ô ÔÔ›Ô˜ÂËÚ¿˙ÂÈ ÙË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à (11). ∏ ·Ú·ÙË-ÚÔ‡ÌÂÓË ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜ (20) ·Ó·ÛÙÔÏ‹ Ù˘

¶›Ó·Î·˜ 1. ∂›Â‰· ÓÙÔ·Ì›Ó˘, ·ÌÈÓÔͤˆÓ Î·È ‰Ú·ÛÙÈÎfiÙËÙ·˜ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ (∞Ã) Û ʷÈÓ˘ÏÎÂÙÔÓÔ˘ÚÈÎÔ‡˜ ·ÛıÂÓ›˜Î·È Ì¿ÚÙ˘Ú˜

OÌ¿‰· ∞ OÌ¿‰· µ ª¿ÚÙ˘Ú˜(¡=12) (¡=11) (¡=23)

º·È (mg/dl) 1,57±0,52· 28,45±1,50‚ 1,45±0,60Á

∆˘Ú (mg/dl) 2,09±0,70· 0,83±0,30‚ 2,13±0,80Á

AÏ· (mg/dl) 4,07±0,60· 3,79±1,0‚ 3,85±1,00Á

¡ÙÔ (Ìmol/l) 137±29· 56±18‚ 142±22Á

AX (¢OD/min x mg protein) 3,01±0,18· 1,19±0,05‚ 3,13±0,16Á

OÈ ÙÈ̤˜ ÂÎÊÚ¿˙ÔÓÙ·È: ª¤ÛË ÙÈÌ‹±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛ˺·È, ∆˘Ú, ¡ÙÔ, AX: ·/‚, ‚/Á=p<0,001 Î·È ·/Á=M™∞Ï·: ·/‚, ·/Á, ‚/Á=ª™ ª™: ªË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ÙÈÌ‹

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¡a+, K+-ATP¿Û˘ ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿-Ó˜ PKU ·ÛıÂÓÒÓ ı· ÌÔÚÔ‡ÛÂ, ›Û˘, Ó· ·Ô-‰Ôı› ÛÙ· ¯·ÌËÏ¿ ›‰· Ù˘ ¡ÙÔ (¶›Ó·Î·˜ 1)(21,22) Î·È ÛÙ· ˘„ËÏ¿ ›‰· ·ÎÂÙ˘Ï¯ÔÏ›Ó˘ (23).∂›Û˘, Ù· ›‰· Ù˘ ·ÎÂÙ˘Ï¯ÔÏ›Ó˘ ı· ÌÔÚÔ‡-Û·Ó Ó· ·˘ÍËıÔ‡Ó ÛÙÔ Ï¿ÛÌ· PKU ·ÛıÂÓÒÓ, fiˆ˜Â›Û˘ ÛÙÔÓ ÔÏÈÎfi ÂÁΤʷÏÔ, ÛÙÔ ‰È¿ÊÚ·ÁÌ· Ô-ÓÙÈÎÔ‡ (8,9) Î·È ÛÂ Û˘ÁÎÂÎÚÈ̤Ó˜ ÂÚÈÔ¯¤˜ ÙÔ˘ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡ (ÚfiÛıÈÔ˜ ÏÔ‚fi˜, Èfiη-ÌÔ˜) (24), ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ·Ó·ÛÙÔÏ‹˜ Ù˘ ∞÷fi ÙË º·È (8,9,24). ∫·Ù¿ Û˘Ó¤ÂÈ·, Ë ‰Ú·ÛÙÈÎfiÙË-Ù· ÙÔ˘ ÂÓ˙‡ÌÔ˘ Na+, K+-ATP¿ÛË ı· ÌÔÚÔ‡ÛÂ, ›-Û˘, Ó· ÌÂȈı› (9,20,24). O Weil-Maiherbe (25)‚ڋΠÌÂȈ̤ӷ Ù· ›‰· Ù˘ ¡ÙÔ ÛÙÔ Ï¿ÛÌ·PKU ·ÛıÂÓÒÓ ¯ˆÚ›˜ ıÂڷ›·. ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿Û˘ÌʈÓÔ‡Ó Ì ÂΛӷ ÙˆÓ PKU ·ÛıÂÓÒÓ Ù˘ ·-ÚÔ‡Û·˜ ÌÂϤÙ˘ Ì ¯·Ï·Ú‹ ‰›·ÈÙ· (ÔÌ¿‰· µ).ŒÙÛÈ, ı· ÌÔÚÔ‡Û·Ì ӷ ˘Ôı¤ÛÔ˘Ì fiÙÈ ·ÓÙÈÚÔ-ÛˆÂ‡Ô˘Ó ÂΛӷ ÙÔ˘ ∂¡À (5,12).

¶·Ú·ÙËÚ‹ıËΠÌÂÁ¿ÏË Ì›ˆÛË (60%) Ù˘ ‰Ú·-ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿-Ó˜ ÙˆÓ PKU ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ µ, Û˘ÁÎÚÈÓfiÌÂ-ÓË Ì ÂΛÓË Ô˘ ÌÂÙÚ‹ıËΠin vitro (20%) ÛÙÔÓÂÁΤʷÏÔ Î·È ÛÙÔ ‰È¿ÊÚ·ÁÌ· ÔÓÙÈÎÔ‡, fiˆ˜ ›-Û˘ ÛÙÔ Î·ı·Úfi ¤Ó˙˘ÌÔ (8,9), ·ÚÔ˘Û›· ˘„ËÏÒÓÂȤ‰ˆÓ º·È. ™˘ÓÂÒ˜, Ë ÌÂÁ¿ÏË ·Ó·ÛÙÔÏ‹ Ù˘∞à ÛÙ· ÂÚ˘ıÚÔ·ÙÙ·Ú· ÙˆÓ ·ÛıÂÓÒÓ Ì·˜ ı· ÌÔ-ÚÔ‡Û ӷ ·Ô‰Ôı› ÛÙËÓ Â› Ì·ÎÚfi ¯ÚfiÓÔ Â›‰Ú·-ÛË Ù˘ º·È ÛÙË ÌÂÌ‚Ú¿ÓË ÙÔ˘ ÂÓ˙‡ÌÔ˘. ™Â Ì›· Úfi-ÛÊ·ÙË ÂÚÁ·Û›· (10) ‰È·ÈÛÙÒıËΠfiÙÈ Ë ∞Ï· ÚÔ-Ê˘Ï¿ÛÛÂÈ ÙËÓ in vitro ·Ó·ÛÙÔÏ‹ Ù˘ ∞à ·fi ÙË º·È,·ÓÙ·ÁˆÓÈ˙fiÌÂÓË ÙÔ ·ÚˆÌ·ÙÈÎfi ·˘Ùfi ·ÌÈÓÔ͇ ÙfiÛÔÛÙÔÓ ÂÁΤʷÏÔ ÔÓÙÈÎÔ‡, fiÛÔ Î·È ÛÙÔ Î·ı·Úfi ¤Ó-˙˘ÌÔ. ¶Ú¿ÁÌ·ÙÈ, ÛÙËÓ ·ÚÔ‡Û· ÂÚÁ·Û›·, Ë ∞Ï·ÚÔÛÙÈı¤ÌÂÓË ÛÙÔ Ì›ÁÌ· ÚÔÂÒ·Û˘ Ù˘ ∞Ã,ÛÙÔ ÔÔ›Ô ÚÔ¸‹Ú¯Â º·È, ÚÔʇϷÍ ÙÔ ¤Ó˙˘ÌÔÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ ÙˆÓ Ì·ÚÙ‡ÚˆÓ·fi ÙËÓ ·Ó·ÛÙ·ÏÙÈ΋ ‰Ú¿ÛË ÙÔ˘. ∞ÓÙ›ıÂÙ·, Ë ∞Ï·‰ÂÓ Î·ÙfiÚıˆÛ ӷ ·ÓÙÈÛÙÚ¤„ÂÈ ÛÙÔ Ê˘ÛÈÔÏÔÁÈÎfiÙËÓ ·Ó·ÛÙ·Ï̤ÓË ∞Ã ÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ-‚Ú·ÓÒÓ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ µ. ∆Ô Â‡ÚËÌ· ·˘Ùfiı· ÌÔÚÔ‡Û ӷ ÂÚÌËÓ¢ı› ·fi ÙËÓ ·‰˘Ó·Ì›··ÓÙ·ÁˆÓÈÛÙÈÎfiÙËÙ·˜ Ù˘ ∞Ï· Ì ÙËÓ º·È ÛÙËÓ ∞Ã,ηı’ fiÛÔÓ Ë ÔÛfiÙËÙ· Ù˘ º·È ÛÙËÓ ÂÚ˘ıÚÔ΢ÙÙ·-ÚÈ΋ ÌÂÌ‚Ú¿ÓË Â›Ó·È ÂÏ¿¯ÈÛÙË (10). ™˘ÓÂÒ˜, Ë Â›

Ì·ÎÚfi ¯ÚfiÓÔ Â›‰Ú·ÛË ÙˆÓ ·˘ÍËÌ¤ÓˆÓ ÂȤ‰ˆÓÙ˘ º·È ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓPKU ·ÛıÂÓÒÓ, ÂӉ¯Ô̤ӈ˜ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ·ÙË Ì›ˆÛË ÙˆÓ ÂÓÂÚÁÒÓ ÂÓ˙˘ÌÈÎÒÓ ÌÔÚ›ˆÓ ÛÙË ÌÂÌ-‚Ú¿ÓË. ∆Ô ÁÂÁÔÓfi˜ ·˘Ùfi ı· ÌÔÚÔ‡Û ӷ ·Ô‰Ô-ı› ÛÙË Ì›ˆÛË Ù˘ ÚˆÙÂ˚ÓÈ΋˜ Û‡ÓıÂÛ˘, Ô˘ÚÔ¤Ú¯ÂÙ·È ·fi Ù· ˘„ËÏ¿ ›‰· Ù˘ º·È (26-28).

∫·ı’ fiÛÔÓ Â›Ó·È ÁÓˆÛÙfi fiÙÈ ÔÈ ‰ÈÂÚÁ·Û›Â˜ Ù˘ÌÓ‹Ì˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ¯ÔÏÈÓÂÚÁÈÎÔ‡˜ Î·È ·‰ÚÂ-ÓÂÚÁÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ (29), fiˆ˜ ›Û˘ fiÙÈ Ë ¯·-ÌËÏ‹ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞Ã Û˘Û¯ÂÙ›˙ÂÙ·È ÛÙÂÓ¿ ÌÂÙ· ÌÂȈ̤ӷ ›‰· Ù˘ ¡ÙÔ Û‡Ìʈӷ Ì ÙËÓ ·-ÚÔ‡Û· ÌÂϤÙË, ı· ÌÔÚÔ‡Û ӷ ˘ÔÛÙËÚȯı› fiÙÈ·˘Ù¿ Ù· Â˘Ú‹Ì·Ù· ÌÔÚÔ‡Ó Û οÔÈÔ ‚·ıÌfi Ó·ÂÚÌËÓ‡ÛÔ˘Ó ÙȘ ‚Ï¿‚˜ ÙˆÓ PKU ·ÛıÂÓÒÓ. ∞Îfi-ÌË, ı· ÌÔÚÔ‡Û ӷ ÂÚÌËÓ¢ı› Î·È Ô ·Ú·ÙËÚÔ‡-ÌÂÓÔ˜ ÙÚfiÌÔ˜ ÛÙÔ˘˜ PKU ·ÛıÂÓ›˜ ¯ˆÚ›˜ ıÂÚ·-›·, ÏfiÁˆ ·‡ÍËÛ˘ Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ·ÎÂ-Ù˘Ï¯ÔÏ›Ó˘, ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ÌÂȈ̤Ó˘ ‰Ú·ÛÙÈ-ÎfiÙËÙ·˜ Ù˘ ∞Ã.

∂˘¯·ÚÈÛٛ˜OÈ Û˘ÁÁÚ·Ê›˜ ıˆÚÔ‡Ó ˘Ô¯Ú¤ˆÛ‹ ÙÔ˘˜ Ó· ¢¯·ÚÈÛÙ‹-

ÛÔ˘Ó ÙËÓ Î·. ∆·ÛÛÔÔ‡ÏÔ˘ ∫·ÏÏÈfiË ÁÈ· ÙËÓ ÂÈÌÂÏË̤Óˉ·ÎÙ˘ÏÔÁÚ¿ÊËÛË Ù˘ ÂÚÁ·Û›·˜.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Scriver C, Kaufman S, Eisensmith R, Woo S. The

hyperphenylalaninemias. In: Scriver C, Beadet A, Sly W,Valle D, editors. The metabolic and molecular bases ofinherited disease. New York, NY: McGraw Hill; 1995. p.1015-1075.

2. Missiou-Tsagaraki S, Soulpi K, Loumakou M.Phenylketonuria in Greece: 12 years experience. J MentDefic Res 1988;32:271-281.

3. Burri R, Steffen C, Stieger S, Brodbeck U, Colombo JP,Herschkowitz N. Reduced myelinogenesis and recovery inhyperphenylalaninemic rats. Correlation between brainphenylalanine levels, characteristic brain enzymes formyelination, and brain development. Mol ChemNeuropathol 1990;13:57-69.

4. Francis D. Diets for sick children. 4th ed. Oxford: BlackwellScientific Publ; 1989. p. 224-255.

¶›Ó·Î·˜ 2. ™˘Û¯ÂÙ›ÛÂȘ ÌÂٷ͇ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ·ÌÈÓÔͤ-ˆÓ º·È, ∆˘Ú, ∞Ï·, Ù˘ ¡ÙÔ Ì ÙË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à Û·ÛıÂÓ›˜ Ì ʷÈÓ˘ÏÎÂÙÔÓÔ˘Ú›· (¡=11)

º·È ∆˘Ú ∞Ï· ¡ÙÔ

∞à -0,58** +0,44* +0,12 +0,46*

* p<0,05** p<0,01

¶›Ó·Î·˜ 3. ¢Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à Û ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ-‚Ú¿Ó˜ Ì·ÚÙ‡ÚˆÓ ÌÂÙ¿ ·fi in vitro ÂÒ·ÛË Ì º·È, ∞Ï· ηȺ·È+∞Ï·

™˘ÁΤÓÙÚˆÛË AX ‰Ú·ÛÙÈÎfiÙËÙ·(mM) (¢OD/min x mg protein)

ª¿ÚÙ˘Ú˜ 0 3,03±0,13º·È 1,8 1,90±0,14***∞Ï· 1,8 2,96±0,21º·È+∞Ï· 1,8 3,10±0,19

*** p<0,001 OÈ ÙÈ̤˜ ÂÎÊÚ¿˙ÔÓÙ·È: ª¤ÛË ÙÈÌ‹±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË

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5. Curtius HC, Niederwieser A, Viscontini M, Leimbacher W,Wegmann H, Blehova B et al. Serotonin and dopaminesynthesis in phenylketonuria. Adv Exp Med Biol1981;133:277-291.

6. Krause W, Halminski M, McDonald L, Dembure P, Salvo R,Freides D et al. Biochemical and neuropsychologicaleffects of elevated plasma phenylalanine in patients withtreated phenylketonuria. J Clin Invest 1985;75:40-48.

7. Fernstrom JD. Dietary amino acids and brain function. J AmDiet Assoc 1994;94:71-77.

8. Tsakiris S, Kouniniotou-Krontiri P, Schulpis KH, StavridisJC. L-phenylalanine effect on rat brain acetylcholine steraseand Na+, K+-ATPase. Z Naturforsch 1998;53c:163-167.

9. Tsakiris S, Kouniniotou-Krontiri P, Schulpis KH. L-phenylalanine effect on rat diaphragm acetylcholine-sterase and Na+, K+-ATPase. Z Naturforsch 1998;53c:1055-1060.

10. Tsakiris S, Schulpis KH. Alanine reverses the inhibitoryeffect of phenylalanine on acetylcholinesterase activity. ZNaturforsch 2002;57c:506-511.

11. Hawkins CA, Greenfield SA. Non-cholinergic action ofexogenous acetylcholinesterase in the rat substantia nigra.II. Long-term interactions with dopamine metabolism.Behav Brain Res 1992;48:159-163.

12. Schulpis KH, Papakonstantinou E, Michelakakis H,Theodoridis T, Papandreou U, Constantopoulos A.Elevated serum prolactin concentrations in phenylketo-nuric patients on a “loose diet”. Clin Endocrinol 1998;48:99-101.

13. Galbraith DA, Watts DC. Changes in some cytoplasmicenzymes from red cells fractionated into age groups bycentrifugation in Ficoll/Triosil gradients. Biochem J1980;191:63-70.

14. Kamber E, Poyiagi A, Deliconstantinos G. Modifications inthe activities of membrane-bound enzymes during in vivoageing of human and rabbit erythrocytes. Comp BiochemPhysiol 1984;77B:95-99.

15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Proteinmeasurement with the Folin phenol reagent. J Biol Chem1951;193:265-275.

16. Ellman GL, Courtney D, Andres V, Featherstone RM. A newa rapid colorimetric determination of acetylcholinesteraseactivity. Biochem Pharmacol 1961;7:88-85.

17. Tsakiris S. Effects of L-phenylalanine on acetylcholine-sterase and Na+, K+-ATPase activities in adult and aged ratbrain. Mech Ageing Dev 2001;122:491-501.

18. Candito M, Albertini M, Politano S, Deville A, Mariani R,Chambon P. Plasma catecholamine levels in children. JChromatogr 1993;617:304-307.

19. Carlson HE, Hyman DB, Blitzer MG. Evidence for anintracerebral action of phenylalanine in stimulation ofprolactin secretion: interaction of large neutral amino acids.J Clin Endocrinol Metab 1990;70:814-816.

20. Bedin M, Estrella CH, Ponzi D, Duarte DV, Dutra-Filho CS,Wyse AT et al. Reduced Na+, K+-ATPase activity inerythrocyte membranes from patients with phenylketo-nuria. Pediatr Res 2001;50:56-60.

21. Bogdanski DF, Tissari A, Brodie BB. Role of sodium,potassium, ouabain and reserpine in uptake, storage andmetabolism of biogenic amines in synaptosomes. Life Sci1968;7:419-428.

22. Swann AC. (Na+, K+)-adenosine triphosphatase regulationby the sympathetic nervous system: effects ofnoradrenergic stimulation and lesion in vivo. J PharmacolExp Ther 1984;228:304-311.

23. Meyer EM, Cooper JR. Correlations between Na+, K+-ATPase activity and acetylcholine release in rat corticalsynaptosomes. J Neurochem 1981;36:467-475.

24. Doulgeraki A, Papadopoulou-Daifoti Z, Tsakiris S. Effects ofL-phenylalanine on acetylcholinesterase and Na+, K+-ATPase activities in suckling rat frontal cortex, hippo-campus and hypothalamus. Z Naturforsch 2002;57c:182-188.

25. Weil-Maiherbe F. Blood adrenaline and intelligence. J MentSci 1995;101:733-754.

26. Antonas KN, Coulson WF. Brain uptake and proteinincorporation of amino acids studied in rats subjected toprolonged hyperphenylalaninaemia. J Neurochem 1975;25:309-314.

27. Taub F, Johnson TC. The mechanism of polyribosomedisaggregation in brain tissue by phenylalanine. Biochem J1975;151:173-180.

28. Hughes JV, Johnson TC. The effect of hyperphenyla-laninaemia on the concentrations of aminoacyl-transferribonucleic acid in vivo. Biochem J 1977;162:527-537.

29. Ohno M, Kobayashi M, Kishi A, Watanabe S. Workingmemory failure by combined blockade of of muscarinic and‚-adrenergic transmission in the rat hippocampus.Neuroreport 1997;8:1571-1575.

HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 18-06-2002HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 17-01-2003

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∫ÏÂÔ¿ÙÚ· ™Ô‡ÏË πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∆.∫. 115 27, ∞ı‹Ó·

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OÚÁ·ÓÈΤ˜ ÔÍ˘Ô˘Ú›Â˜ ÛÙËÓ ∂ÏÏ¿‰· - ÂÌÂÈÚ›· ¤ÍÈ ¯ÚfiÓˆÓ. ∫ÏÈÓÈ΋ Î·È ‚ÈÔ¯ËÌÈ΋ ÚÔÛ¤ÁÁÈÛË °. ª·ÚfiÔ˘ÏÔ˜1, ¶. ∞˘ÁÔ˘ÛÙ›‰Ô˘ - ™·‚‚ÔÔ‡ÏÔ˘2, ∫. µÔ‡‰Ú˘3, ∫. ™Ô‡ÏË4, ™. ª¿ÛÙÔÚ·1, ∂. ¢ÚÔÁοÚË5

Organic acidurias in Greece - 6 years’ experience. Clinical and biochemical approach G. Maropoulos1, P. Augoustides - Savvopoulou2, K. Voudris3, K. Soulpi4, S. Mastora1, E. Drogari5

∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞ ORIGINAL ARTICLE

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�¶ÂÚ›ÏË„Ë: ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ÛÙËÓ ∂ÏÏ¿‰·, ËÂÚÁ·ÛÙËÚȷ΋ ‰ÈÂÚ‡ÓËÛË ÙˆÓ ÎÏËÚÔÓÔÌÈÎÒÓ ÌÂ-Ù·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ (∫ª¡) ‰È¢ڇÓÂÙ·È. ∆· ∫ª¡ÔÊ›ÏÔÓÙ·È Û ÁÂÓÂÙÈο ηıÔÚÈ˙fiÌÂÓ˜ ÂÓ˙˘ÌÈΤ˜ ‹¿ÏϘ ÚˆÙÂ˚ÓÈΤ˜ ·Ó¿ÚÎÂȘ ‚ÈÔ¯ËÌÈÎÒÓ ·ÓÙÈ-‰Ú¿ÛÂˆÓ ÙÔ˘ ÂӉȿÌÂÛÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡. ∆· ÓÔÛ‹-Ì·Ù· ·˘Ù¿ ¤¯Ô˘Ó ÛËÌ·ÓÙÈ΋ ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ·Î·È Û˘Ó‹ıˆ˜ ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÎÏÈÓÈο ÛÙËÓ ·È‰È΋ËÏÈΛ· Ì ÔÈÎÈÏÔÌÔÚÊ›· ÂΉËÏÒÛˆÓ. ∂ȉÈ΋ ÔÌ¿-‰· ∫ª¡ Â›Ó·È ÔÈ ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÌÂÙ·‚ÔÏÈ-ÛÌÔ‡ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, ÂӉȿÌÂÛ· ÚÔ˚fiÓÙ·ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ·ÌÈÓÔͤˆÓ, ÙˆÓ ÏÈ·ÚÒÓÔͤˆÓ Î·È ÙˆÓ ˘‰·Ù·ÓıڿΈÓ. OÈ ·ÛıÂÓ›˜ ·˘ÙÒÓÙˆÓ ·Ó·ÚÎÂÈÒÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂȉÈΤ˜ ÎÏÈÓÈΤ˜ÂΉËÏÒÛÂȘ Ì ¯·Ú·ÎÙËÚÈÛÙÈ΋ ·¤ÎÎÚÈÛË ÔÚÁ·ÓÈ-ÎÒÓ ÔͤˆÓ. ∏ ·ÍÈÔÔ›ËÛË ÙˆÓ Ù¯ÓÈÎÒÓ Ù˘ Ê·-ÛÌ·ÙÔÁÚ·Ê›·˜ Ì·˙ÒÓ (MS) Î·È Ù˘ ·¤ÚÈ·˜ ¯ÚˆÌ·-ÙÔÁÚ·Ê›·˜ (GC) ÛÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÔÚÁ·ÓÈ-ÎÒÓ ÔͤˆÓ ·ÔηχÙÂÈ ÙÔÓ Ù‡Ô Ù˘ ÔÚÁ·ÓÈ΋˜Ô͢Ԣڛ·˜. ∆ËÓ ÂÚ›Ô‰Ô 1996-2001 ·Ó·Ï‡ıËÎ·Ó ÌÂÚÔÙ˘ÔÔÈË̤ÓË ÌÂıÔ‰ÔÏÔÁ›· GC-MS, ‰Â›ÁÌ·Ù·Ô‡ÚˆÓ ·fi 5021 ·ÛıÂÓ›˜ Ì ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔ-ÏÔÁ›· Èı·ÓÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜.∞fi ÙȘ ·Ó·Ï‡ÛÂȘ ‰È·ÈÛÙÒıËΠ۠85 ·ÛıÂÓ›˜ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· ‰È·ÁÓˆÛÙÈ΋ ∫ª¡. ∂ȉÈÎfiÙÂÚ·,Û 46 ·ÛıÂÓ›˜ ‰È·ÈÛÙÒıËÎ·Ó 12 ·Ó¿ÚÎÂȘ ÙÔ˘ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ‹ Ù˘ ‚-ÔÍ›-‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ. ™Â 13 ·ÛıÂÓ›˜ Ì ÙÔÍÈ΋

�Abstract: Selective screening for inheriteddefects of organic acid metabolism is acontinuously expanding diagnostic procedure inGreece. The diagnosis of the organic acidurias, ahigh incidence group of inborn errors of meta-bolism (IEM), is based primarily on identification ofthe organic acid profile in the urine and/oracylcarnitine profile abnormalities in the bloodusing gas chromatography-mass spectrometry(GC-MS) and tandem mass spectrometry respec-tively. The in time diagnosis of the majority of thesedisorders is critical for early initiation of effectivetreatment and improved prognosis. The last sixyears, urine and blood specimens of 5021 patientsat high risk for IEM, in particular defects of organicacid metabolism, were investigated in the ClinicalBiochemistry Laboratory of the “P. & A. Kyriakou”Children’s Hospital. IEM were diagnosed in 85patients, specifically, MMA (8), propionic acidemia(3), glutaric aciduria type I (6), SSADH (6), L-2-hydroxy-glutaric aciduria (4), Canavan disease (2),HMGlyase deficiency (2), ‚-ketothiolase deficiency(1), EPEMA syndrome (1), MADD (1), MCADdeficiency (7) and 5 cases with dicarboxylicaciduria and abnormal acylcarnitine profileanalyses. Thirteen patients presented with toxichyperammonemia (6 cases of OTC, 1 of ASS, 4 ofLPI and 2 with persistent mild orotic aciduria), 10

1 µÈÔ¯ËÌÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·

2 µÈÔ¯ËÌÈÎfi ∂ÚÁ·ÛÙ‹ÚÈÔ ∞’ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ∞¶£,°¶¡ πÔÎÚ¿ÙÂÈÔ, £ÂÛÛ·ÏÔÓ›ÎË

3 ¡Â˘ÚÔÏÔÁÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·

4 πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á. ™ÔÊ›·”, ∞ı‹Ó·

5 ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á. ™ÔÊ›·”, ∞ı‹Ó·

1 Department of Biochemistry, “P. & A. Kyriakou” Children’s Hospital, Athens

2 Biochemistry Laboratory, 1st Pediatric Clinic of AristotelionUniversity, Ippokration Hospital, Thessaloniki

3 Department of Neurology, “P. & A. Kyriakou” Children’s Hospital, Athens

4 Institute of Child Health, “Ag. Sophia” Children’s Hospital, Athens

5 1st Pediatric Clinic of Athens University, “Ag. Sophia” Children’s Hospital, Athens

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∂ÈÛ·ÁˆÁ‹∆· ÎÏËÚÔÓÔÌÈο ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· (∫ª¡-

Inherited metabolic disorders) ·ÔÙÂÏÔ‡Ó ÌÂÁ¿ÏËÎ·È ‰È·ÚÎÒ˜ ·˘Í·ÓfiÌÂÓË ÔÌ¿‰· ÓÔÛËÌ¿ÙˆÓ ÌÂ Û˘-¯Ó¿ ÛÔ‚·Ú¤˜ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÛÙË ÓÂÔÁÓÈ΋,‚ÚÂÊÈ΋ Î·È ·È‰È΋ ËÏÈΛ· (1). ∞ÚÎÂÙ¿ ·fi ·˘Ù¿·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎfi ·›ÙÈÔ ÚfiÎÏËÛ˘ ÓÔÛËÚfiÙË-Ù·˜ Î·È ıÓËÙfiÙËÙ·˜, ȉȷ›ÙÂÚ· ÛÙÔÓ ·È‰ÈÎfi ÏËı˘-ÛÌfi (2). ŸÌˆ˜, Ë ¤ÁηÈÚË ‰È·ÁÓˆÛÙÈ΋ ‰ÈÂÚ‡ÓËÛ‹ÙÔ˘˜ ÂÈÙÚ¤ÂÈ ÙËÓ ÂÊ·ÚÌÔÁ‹ Û˘¯Ó¿ ·ÔÙÂÏÂÛÌ·ÙÈ-΋˜ ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹˜ Î·È ÚÔÁÂÓÓËÙÈÎÔ‡ ÂϤÁ-¯Ô˘. ™ÙËÓ ÔÌ¿‰· ÙˆÓ ∫ª¡ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ¿Óˆ·fi 469 ÓÔÛ‹Ì·Ù· Î·È Û‡Ìʈӷ Ì ÙËÓ Â˘Úˆ·˚΋

Ù·ÍÈÓfiÌËÛË ÙˆÓ ÓÔÛËÌ¿ÙˆÓ ·Ó‹ÎÔ˘Ó ÛÙËÓ Î·ÙËÁÔ-Ú›· ÙˆÓ Û¿ÓÈˆÓ ÓÔÛËÌ¿ÙˆÓ (rare disorders ororphan diseases) (3). ¶·Ú’ fiÏ· ·˘Ù¿, Ë ·ıÚÔÈÛÙÈÎ‹Û˘¯ÓfiÙËÙ¿ ÙÔ˘˜ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, Û‡ÌʈӷÌ ‰È¿ÊÔÚ˜ ÌÂϤÙ˜, Â›Ó·È ÌÂٷ͇ 1:600-2000 ÁÂÓ-Ó‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ (3-5). OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒ-ÛÂȘ ÙÔ˘˜ ÔÊ›ÏÔÓÙ·È Û ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ (inborn errors ofmetabolism), ÔÈ Ôԛ˜ ÚÔηÏÔ‡ÓÙ·È ·fi Û˘ÁÎÂ-ÎÚÈ̤Ó˜ ÂÓ˙˘ÌÈΤ˜ ·Ó¿ÚÎÂȘ ‹ ·fi ÙË Û‡ÓıÂÛËÂÏ·Ùو̷ÙÈ΋˜ ‰ÔÌ‹˜ Î·È ÏÂÈÙÔ˘ÚÁ›·˜ ÚˆÙÂ˚ÓÒÓ(6). ∞›ÙÈÔ ·˘ÙÒÓ ÙˆÓ ·Ó·ÚÎÂÈÒÓ Â›Ó·È Û˘ÁÎÂÎÚÈ̤-Ó˜ ÌÔÓÔÁÔÓȉȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ (Mendelian

˘ÂÚ·Ì̈ÓÈ·ÈÌ›· Î·È ÔÚÔÙÈ΋ Ô͢Ԣڛ·, Ù·˘ÙÔÔÈ-‹ıËΠÂÓ˙˘ÌÈ΋ ·Ó¿ÚÎÂÈ· ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜Î·È Ï˘ÛÈÓÔ˘ÚÈ΋ ‰˘Û·ÓÂÍ›· ÛÙËÓ ÚˆÙ½ÓË (4 ·ÛıÂ-Ó›˜). ∞ÌÈÓÔ-ÔÍ˘Ô¿ıÂÈ· (·ÏηÙÔÓÔ˘Ú›·, ÓfiÛÔ˜ ÌÂÔÛÌ‹ Ô‡ÚˆÓ Û·Ó ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘, Ù˘ÚÔÛÈ-Ó·ÈÌ›· Ù‡Ô˘ π) ›¯·Ó 10 ·ÛıÂÓ›˜. O ·ÚÈıÌfi˜ ·˘-ÙÒÓ ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ, Ô ÔÔ›Ô˜ ·ÓÙÈ-ÛÙÔȯ› Û ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ· 1:8696 ÁÂÓÓ‹ÛÂȘÙ˘ Û˘ÁÎÂÎÚÈ̤Ó˘ ÂÚÈfi‰Ô˘ ÛÙË ¯ÒÚ·, ·ÔÙÂÏ›¤Ó·Ó ÚÒÙÔ ‰Â›ÎÙË Ù˘ ¤ÎÊÚ·Û‹˜ ÙÔ˘˜ ÛÙÔÓ ÂÏÏË-ÓÈÎfi ÏËı˘ÛÌfi. ∂ÈϤÔÓ, Ô ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ-¯Ô˜ Ô˘ Ú·ÁÌ·ÙÔÔÈ‹ıËÎÂ Û˘Ó¤‚·Ï ÛÙË ‰ÈÂÚ‡-ÓËÛË ¿ÏÏˆÓ Î·ÙËÁÔÚÈÒÓ ∫ª¡ Ô˘ Ù·˘ÙÔÔÈÔ‡ÓÙ·ÈÌ ¿ÏϘ Ù¯ÓÈΤ˜. ∞Ó¢Ú‡ıËÛ·Ó 2 ·ÛıÂÓ›˜ Ì·Ó¿ÚÎÂȘ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ Ô˘ÚÈÓÒÓ Î·ÈÙˆÓ ˘ÚÈÌȉÈÓÒÓ Î·È 14 ·ÛıÂÓ›˜ Ì ÂÓ˙˘ÌÈΤ˜ ·ÓÂ-¿ÚÎÂȘ ÚˆÙÔ·ıÔ‡˜ Á·Ï·ÎÙÈ΋˜ ÌÂÙ·‚ÔÏÈ΋˜ÔͤˆÛ˘ (·Ó¿ÚÎÂȘ Û˘ÌÏÂÁÌ¿ÙˆÓ ·Ó·Ó¢ÛÙÈ-΋˜ ·Ï‡ÛÔ˘ Û 9 ·ÛıÂÓ›˜ Î·È ·Ó¿ÚÎÂÈ· ˘ÚÔ-ÛÙ·Ê˘ÏÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘ Û 4 ·ÛıÂÓ›˜). ∞Îfi-ÌË, Û 247 ·ÛıÂÓ›˜ (5,3% ÙˆÓ ·Ó·Ï‡ÛˆÓ), ÛÙÔÊ¿ÛÌ· ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ‰È·ÈÛÙÒıËÎ·Ó ÂÓ‰ÂÈ-ÎÙÈΤ˜ Î·È fi¯È ‰È·ÁÓˆÛÙÈΤ˜ ‰È·Ù·Ú·¯¤˜. ™ÙË ÌÂϤ-ÙË ·Ú¤¯ÔÓÙ·È ÎÏÈÓÈΤ˜ ÏËÚÔÊÔڛ˜ ÛÙÔ 70% ÙˆÓ·ÛıÂÓÒÓ Ô˘ ÂÍÂÙ¿ÛıËηÓ. ∆Ô 63,3% ÙˆÓ ·ÛıÂÓÒÓ·ÚÔ˘Û›·Û ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·-ÙÔ˜. OÈ ÂÚÈÛÛfiÙÂÚÔÈ ÂÍ ·˘ÙÒÓ Â›¯·Ó ¯·Ú·ÎÙËÚÈÛÙÈ-ο ¯ÚfiÓÈ·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜. ™˘Ìو̷ÙÔÏÔÁ›·ÔÍ›·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ ·ÚÔ˘Û›·Û ÙÔ 4,3% ÙˆÓ·ÛıÂÓÒÓ. ¢È·Ù·Ú·¯¤˜ ۈ̷ÙÈ΋˜ ·Ó¿Ù˘Í˘ ·-ÚÔ˘Û›·˙ ÙÔ 8,7% Î·È ÂȉÈΤ˜ ۈ̷ÙÈΤ˜ ÔÚÁ·ÓÈΤ˜‚Ï¿‚˜ ÙÔ 26,4%. ∆· ·Ú·¿Óˆ Â˘Ú‹Ì·Ù· Û¯ÔÏÈ¿-˙ÔÓÙ·È ·fi ÎÏÈÓÈ΋ Î·È ‚ÈÔ¯ËÌÈ΋ ÛÎÔÈ¿, Ì ÛÙfi¯ÔÙË ‚ÂÏÙ›ˆÛË Ù˘ ‰È¿ÁÓˆÛ˘ ·ÛıÂÓÒÓ Ì ÎÏËÚÔÓÔ-ÌÈΤ˜ ÔÚÁ·ÓÈΤ˜ ÔÍ˘Ô˘Ú›Â˜ ÛÙËÓ ∂ÏÏ¿‰·.

§¤ÍÂȘ ÎÏÂȉȿ: ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·,ÔÚÁ·ÓÈΤ˜ ÔÍ˘Ô˘Ú›Â˜, ·¤ÚÈ· ¯ÚˆÌ·ÙÔÁÚ·Ê›·-Ê·-ÛÌ·ÙÔÁÚ·Ê›· Ì·˙ÒÓ.

patients had an amino acid disorder, namely,alkaptonuria (5), MSUD (3), tyrosinemia type I (2),and one patient had a pyrimidine disorder (DPDdeficiency). These diagnoses indicate that thecumulative incidence of these disorders in Greececould be greater than 1:8696 births. In addition, 14patients with primary lactic metabolic acidosis wereidentified and one with abnormalities of purinemetabolism. Evaluation of the data shows a ratherlow diagnostic rate (about 1.67% of the patientsstudied). In addition to the specific diagnoses,significant urine organic acid abnormalities werefound in 247 cases, with no defined cause. Themain clinical symptoms of the patients examinedwere neurological disturbances, accounting for63.3% of patients, the majority of which presentedwith indicative findings of chronic encephalopathy,and 4.3% with acute encephalopathy. Develop-mental delay and dysmorphic features were presentin the 8.7% of the patients and organ failure in26.4%. The clinical and laboratory findings of thisstudy are presented with a view to increasing theawareness of the practicing pediatrician andimproving healthcare planning in Greece to ensureeffective diagnosis.

Key words: inborn errors of metabolism, organicacidurias, metabolic decompensation, gaschromatography-mass spectrometry.

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inheritance, single-gene defects), ‚¿ÛÂÈ ÙˆÓ ÔÔ›ˆÓÎ·È Ù·ÍÈÓÔÌÔ‡ÓÙ·È ¤Ú·Ó Ù˘ ÎÏÈÓÈ΋˜ ÙÔ˘˜ ·Ó·ÊÔ-Ú¿˜ (7). ∏ Û˘Ó‹ı˘ ·Ó·ÊÔÚ¿ ÙˆÓ ∫ª¡ Ù· ÔÚ›˙ÂÈ‚¿ÛÂÈ Ù˘ ÚˆÙ·Ú¯È΋˜ ‚ÈÔ¯ËÌÈ΋˜ ‹ ΢ÙÙ·ÚÈ΋˜·Ó¿ÚÎÂÈ·˜ ‹ Î·È ÙˆÓ ÔÚÁ·ÓÈÎÒÓ Û˘ÓÂÂÈÒÓ Ù˘ÚÔηÏÔ‡ÌÂÓ˘ ‚Ï¿‚˘ (.¯. ÌÈÙÔ¯ÔÓ‰Úȷ΋ ÂÁÎÂ-Ê·ÏÔ¿ıÂÈ·). ∏ ‰È·ÁÓˆÛÙÈ΋ ‰ÈÂÚ‡ÓËÛ‹ ÙÔ˘˜ ›ӷÈÛ˘¯Ó¿ ‰˘Û¯ÂÚ‹˜ Î·È ÚÔÛÂÁÁ›˙ÂÙ·È Ì ·ÏÏËÏÔ˘¯›·ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ·Ó·Ï‡ÛˆÓ. ™Ù· ÂÚÈÛÛfiÙÂÚ· ÓÔ-Û‹Ì·Ù·, Ë ‰È¿ÁÓˆÛË ÙÂÎÌËÚÈÒÓÂÙ·È Ì ÙÔÓ ÚÔÛ-‰ÈÔÚÈÛÌfi Ù˘ ÂÓ˙˘ÌÈ΋˜ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÙÔ˘ ÂÏÂÁ¯fi-ÌÂÓÔ˘ ÂÓ˙‡ÌÔ˘ ‹ Ù˘ ·Ó›¯Ó¢Û˘ Ù˘ ÚˆÙÂ˚ÓÈ΋˜·Ó¿ÚÎÂÈ·˜ Î·È Ù˘ ·Ó‡ÚÂÛ˘ Ù˘ ˘Â‡ı˘Ó˘ ÁÔ-Óȉȷ΋˜ ÌÂÙ¿ÏÏ·Í˘. ™Â Ï›Á˜ ÂÚÈÙÒÛÂȘ, Ë ÁÔÓÈ-‰È·Î‹ ÌÂÙ¿ÏÏ·ÍË Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙÔÓ ÎÏÈÓÈÎfi ηȂÈÔ¯ËÌÈÎfi Ê·ÈÓfiÙ˘Ô ÙˆÓ ÓÔÛËÌ¿ÙˆÓ (6).

∆· ∫ª¡ Ô˘ ÔÊ›ÏÔÓÙ·È Û ·Ó¿ÚÎÂÈ· ÙÔ˘ ÌÂ-Ù·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÂÓÂÚÁÔÔÈËÌ¤ÓˆÓ ÌÂ Û˘Ó¤Ó˙˘ÌÔ ∞ηڂÔ͢ÏÈÎÒÓ ÔͤˆÓ (-CoA) ÛÙ· ÌÈÙÔ¯fiÓ‰ÚÈ·, ÔÈ·ÔηÏÔ‡ÌÂÓ˜ ÔÚÁ·ÓÈΤ˜ Ô͢ԷÈ̛˜ ‹ ÔÍ˘Ô˘Ú›Â˜‹ ÔÍ˘Ô¿ıÂȘ (8), ·ÔÙÂÏÔ‡Ó ÔÌ¿‰· ÓÔÛËÌ¿ÙˆÓÛËÌ·ÓÙÈ΋˜ Û˘¯ÓfiÙËÙ·˜ Î·È ÂȉÈÎÒÓ ÎÏÈÓÈÎÒÓ ÂΉË-ÏÒÛˆÓ. ÷ڷÎÙËÚ›˙ÔÓÙ·È ·fi ÙËÓ ·Ú·ÁˆÁ‹ ηȷ¤ÎÎÚÈÛË ÌÂÁ¿ÏˆÓ Û˘ÁÎÂÓÙÚÒÛÂˆÓ Î·Ú‚Ô͢ÏÈ-ÎÒÓ ÔͤˆÓ. ∂ÈÚfiÛıÂÙ· ÙˆÓ ·ÓˆÙ¤Úˆ ÎÏ·ÛÈοÔÚÈ˙fiÌÂÓˆÓ ÔÚÁ·ÓÈÎÒÓ Ô͢ԢÚÈÒÓ, ¿ÏϘ ÂÓ˙˘ÌÈΤ˜·Ó¿ÚÎÂȘ ÚÔηÏÔ‡Ó ÙËÓ ·˘ÍË̤ÓË ·Ú·ÁˆÁ‹Î·È ·¤ÎÎÚÈÛË ÔÈΛÏ˘ ‰ÔÌ‹˜ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ¯ˆÚ›˜ ·ÌÈÓÈ΋ ÔÌ¿‰·, Ë ·Ó›¯Ó¢ÛË ÙˆÓ ÔÔ›ˆÓ ¤¯ÂȉȷÁÓˆÛÙÈ΋ ·Í›·. ™¯ÂÙÈο ·Ó·Ê¤ÚÔÓÙ·È ·Ó¿ÚÎÂÈ-˜ ÙÔ˘ ÂӉȿÌÂÛÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ·ÌÈÓÔͤˆÓ,Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ, ÙˆÓ ˘‰·Ù·Ó-ıڿΈÓ, ÙˆÓ ‚ÈÙ·ÌÈÓÒÓ, ÙˆÓ ˘ÚÈÌȉÈÓÒÓ, ÙˆÓ Ó¢-Úԉȷ‚È‚·ÛÙÒÓ, ÙˆÓ ÈÛÔÚÂÓÔÂȉÒÓ Î·È Ù˘ ¯ÔÏË-ÛÙÂÚfiÏ˘. ™ÙȘ ÔÚÁ·ÓÈΤ˜ ÔÍ˘Ô˘Ú›Â˜, ÔÈ ÎÏÈÓÈΤ˜‰È·Ù·Ú·¯¤˜ Û˘ÓËı¤ÛÙÂÚ· ÔÊ›ÏÔÓÙ·È ÛÙËÓ ÙÔÍÈ΋›‰Ú·ÛË Û “·ÙÙ·Ú· ÛÙfi¯Ô˘˜” ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓÚÔ˚fiÓÙˆÓ Ù˘ ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ‹ ÛÙËÓ ¤Ï-ÏÂÈ„Ë Ù˘ ·Ú·ÁˆÁ‹˜ ÂÓÂÚÁÂÈ·ÎÒÓ ˘ÔÛÙڈ̿-ÙˆÓ. ¶·Ú¿ÁÔÓÙ˜ fiˆ˜ Ë ‰È·ÙÚÔÊ‹, ÔÈ ÏÔÈÌÒÍÂȘ, Ô˘ÚÂÙfi˜, Ë ÓËÛÙ›·, Ë ¿ÛÎËÛË, ÙÔ ¿Á¯Ô˜ ‹ Ë Ù·¯Â›··Ó¿Ù˘ÍË, ÂÈ‚·Ú‡ÓÔ˘Ó ÙȘ ÌÂÙ·‚ÔÏÈΤ˜ ÏÂÈÙÔ˘Ú-Á›Â˜ Î·È ˘ÚÔ‰ÔÙÔ‡Ó ÛÔ‚·Ú¤˜ ÎÏÈÓÈΤ˜ ‰È·Ù·Ú·¯¤˜(6). OÈ ÂÓ ÏfiÁˆ ÂÓ˙˘ÌÈΤ˜ ·Ù¤ÏÂȘ ÌÂÙ·‚È‚¿˙ÔÓÙ·ÈÌ ÙÔÓ ˘ÔÏÂÈfiÌÂÓÔ ÛˆÌ·ÙÈÎfi ¯·Ú·ÎÙ‹Ú· Î·È ÔÚÈ-Ṳ̂Ó˜ ÌÂ Ê˘ÏÔÛ‡Ó‰ÂÙÔ ˘ÔÏÂÈfiÌÂÓÔ. ∏ Û˘¯ÓfiÙË-Ù· ÙˆÓ ÔÚÁ·ÓÈÎÒÓ Ô͢ԢÚÈÒÓ Â›Ó·È ·ıÚÔÈÛÙÈο ÛË-Ì·ÓÙÈ΋ (9,10). ™‡Ìʈӷ Ì ÂÚ¢ÓËÙÈΤ˜ ·Ó·ÊÔÚ¤˜ÛÂ Â˘Úˆ·˚Τ˜ ¯ÒÚ˜, Î˘Ì·›ÓÔÓÙ·È ·fi 1:2500 ¤ˆ˜Î·È 1:20000 ÁÂÓÓ‹ÛÂȘ.

∏ ‰È·ÁÓˆÛÙÈ΋ ÚÔۤϷÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ Ô͢Ô-·ıÂÈÒÓ Â›Ó·È Û¯ÂÙÈο ¢¯ÂÚ‹˜ Ì ÙË ¯Ú‹ÛË ÙˆÓ ÙÂ-¯ÓÈÎÒÓ Ù˘ ·¤ÚÈ·˜ ¯ÚˆÌ·ÙÔÁÚ·Ê›·˜-Ê·ÛÌ·ÙÔÁÚ·-Ê›·˜ Ì·˙ÒÓ (GC-MS), ΢ڛˆ˜ Ì ÙËÓ ·Ó¿Ï˘ÛË ‰Â›ÁÌ·-

ÙÔ˜ Ô‡ÚˆÓ ÙˆÓ ·ÛıÂÓÒÓ (11). ¶¿Óˆ ·fi 65 ‰È·ÁÓˆ-ÛÙÈο ÚÔÊ›Ï ‰È·Ù·Ú·¯ÒÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ·fi 100‰È·ÊÔÚÂÙÈΤ˜ ÎÏËÚÔÓÔÌÈΤ˜ ÂÓ˙˘ÌÈΤ˜ ·Ù¤ÏÂȘ ‰È·-ÎÚ›ÓÔÓÙ·È Ì ÙËÓ ÎÏ·ÛÈ΋ ÌÂıÔ‰ÔÏÔÁ›· Ù˘ ·Ó¿Ï˘Û‹˜ÙÔ˘˜ (12). ∏ ‰˘Ó·ÙfiÙËÙ· ‰È¿ÁÓˆÛ˘ ·˘Í¿ÓÂÙ·È Ì ÂÈ-‰ÈΤ˜ Ù¯ÓÈΤ˜ ·Ó¿Ï˘Û˘ ÙˆÓ Û˘Ó‰Â‰ÂÌ¤ÓˆÓ Ì ÁÏ˘-ΛÓË ‹ ηÚÓÈÙ›ÓË ÔÚÁ·ÓÈÎÒÓ Î·È ÏÈ·ÚÒÓ ÔͤˆÓ (13).

™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ›ӷÈ: ·) Ë ·-Ú¿ıÂÛË ·ıÚÔÈÛÙÈο, ηٿ ÔÌ¿‰Â˜ ÙˆÓ Î‡ÚÈˆÓ ÎÏÈÓÈ-ÎÒÓ ÂΉËÏÒÛÂˆÓ ÙˆÓ ·ÛıÂÓÒÓ, ‰Â›ÁÌ·Ù· ÙˆÓ ÔÔ›-ˆÓ ÂÍÂÙ¿ÛÙËÎ·Ó ÛÙÔ ÂÚÁ·ÛÙ‹ÚÈÔ, ‚) Ë ·ÚÔ˘Û›·ÛËÙˆÓ ‰È·ÁÓˆÛÙÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ Ù˘ ·Ó¿Ï˘Û˘ ÙÔ˘Ê¿ÛÌ·ÙÔ˜ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓ ÛÙ·‰Â›ÁÌ·Ù· ÙˆÓ ·ÛıÂÓÒÓ. ∞ÍÈÔÏÔÁÔ‡ÓÙ·È, ›Û˘, ÌÂÂÈÏÂÎÙÈ΋ ‰ÈÂÚ‡ÓËÛË, Ù· Â˘Ú‹Ì·Ù· ÙˆÓ ·Î˘ÏÔηÚ-ÓÈÙÈÓÒÓ ÙÔ˘ ·›Ì·ÙÔ˜ (14) Î·È Á) Ë ·Ú¿ıÂÛË ÛÙÔȯ›-ˆÓ Î·È ÂÌÂÈÚÈÎÒÓ ·Ú·ÙËÚ‹ÛÂˆÓ Ô˘ ‰È¢ÎÔχÓÔ˘ÓÙËÓ ÎÏÈÓÈ΋ Î·È ÂÚÁ·ÛÙËÚȷ΋ ÚÔÛ¤ÁÁÈÛË ÙˆÓ ÓÔÛË-Ì¿ÙˆÓ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ∂ÍÂÙ¿ÛÙËÎ·Ó ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ ·fi 5021 ·ÛıÂÓ›˜, 2834

·ÁfiÚÈ· (56,5%) Î·È 2187 (43,5%) ÎÔÚ›ÙÛÈ·. ∏ ËÏÈΛ· Û 3342·fi ÙÔ˘˜ ÂÍÂÙ·Ûı¤ÓÙ˜ ·ÛıÂÓ›˜ ‹Ù·Ó: οو ÙˆÓ 2 ÌËÓÒÓ ÛÂ311 ·ÛıÂÓ›˜ (9,31%), 2 ÌËÓÒÓ Ì¤¯ÚÈ 2 ÂÙÒÓ Û 1326 ·ÛıÂ-Ó›˜ (39,7%), 2-6 ÂÙÒÓ Û 936 ·ÛıÂÓ›˜ (28%), ÂÓÒ 769 ·ÛıÂ-Ó›˜ (23%) ›¯·Ó ËÏÈΛ· ¿Óˆ ·fi 6 ÂÙÒÓ. ¶ÔÛÔÛÙfi 10,6%ÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó ÌÂÙ·Ó¿ÛÙ˜. ™ÙÔ Û˘Óԉ¢ÙÈÎfi ÂÓËÌÂÚˆÙÈ-Îfi ÛËÌ›ˆÌ· 3539 ‰ÂÈÁÌ¿ÙˆÓ ·ÛıÂÓÒÓ (70,5% ÙÔ˘ Û˘ÓfiÏÔ˘),·Ó·Ê¤ÚÔÓÙ·È ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ηٿ Û‡ÛÙËÌ·, ˆ˜ ÂÍ‹˜(¶›Ó·Î·˜ 1):

∞) ¢È·Ù·Ú·¯¤˜ ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÛÂ2240 ·ÛıÂÓ›˜ (63,3%). ∏ ÌÂÁ¿ÏË ÏÂÈÔÓfiÙËÙ· ·˘ÙÒÓ ÙˆÓ·ÛıÂÓÒÓ ·ÚÔ˘Û›·˙ ¯ÚfiÓȘ Ó¢ÚÔÏÔÁÈΤ˜ ÂΉËÏÒÛÂȘ(¯ÚfiÓÈ· ÂÁÎÂÊ·ÏÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·). OÍ›· ÂÁÎÂÊ·ÏÈ΋ ‰˘-ÛÏÂÈÙÔ˘ÚÁ›· ·Ó·Ê¤ÚÂÙ·È Û 154 ·ÛıÂÓ›˜ (4,3%).

µ) ¶ÚÔÂÍ¿Ú¯Ô˘Û· ÂÈÎfiÓ· ‰˘ÛÌÔÚÊ›·˜ ‹ ‰˘ÛϷۛ˜ ÛÂ55 ·ÛıÂÓ›˜ (1,5%).

°.1) ¢È·Ù·Ú·¯¤˜ ¿ÏÏˆÓ ÔÚÁ·ÓÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ Û 935·ÛıÂÓ›˜ (26,4%).

°.2) ¢˘ÛÙÚÔÊ›· ‹ ÛÙ·ÛÈÌfiÙËÙ· ‚¿ÚÔ˘˜ Û 309 ·ÛıÂÓ›˜(8,7%).

°.3) ¢Â›ÁÌ·Ù· ·fi 260 ·ÛıÂÓ›˜ (7,3%) ·Ú·¤ÌÊıËηÓÁÈ· ÙË ‰ÈÂÚ‡ÓËÛË ÛËÌ·ÓÙÈÎÒÓ ‚ÈÔ¯ËÌÈÎÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·-Ù·Ú·¯ÒÓ. ¶ÔÏ˘Û˘ÛÙËÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ ·Ó·Ê¤ÚÔÓÙ·È ÛÂ176 ·ÛıÂÓ›˜ (5%) Î·È ‡ÔÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi Û 78·ÛıÂÓ›˜.

∏ Ï‹„Ë ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ ·fi Ôͤˆ˜ ¿Û¯ÔÓÙ˜ ·ÛıÂÓ›˜(› ÔÍ›·˜ ÂÌÊ¿ÓÈÛ˘ Ó¢ÚÔÏÔÁÈÎÒÓ Û˘Ìو̿وÓ, ÂÂÈÛÔ-‰›ˆÓ Ì˘·ÏÁ›·˜ Î·È ÂΉËÏÒÛÂˆÓ ·fi ÙÔ ÂÙÈÎfi Î·È ÙÔ ·Ó·-Ó¢ÛÙÈÎfi Û‡ÛÙËÌ·) ¤ÁÈÓ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÂÂÈÛÔ‰›Ô˘.ŸÌˆ˜, Ë ‰ÂÈÁÌ·ÙÔÏË„›· ‰ÂÓ Û˘Ó¤ÈÙ ¿ÓÙ· Ì ÙËÓ ÂÌÊ¿ÓÈ-ÛË Ù˘ ·‰Ú‹˜ ÌÂÙ·‚ÔÏÈ΋˜ ‰È·Ù·Ú·¯‹˜, ˘ÔÁÏ˘Î·ÈÌ›·˜,˘ÂÚ·Ì̈ÓÈ·ÈÌ›·˜, ΤوÛ˘ ‹ ÌÂÙ·‚ÔÏÈ΋˜ ÔͤˆÛ˘. ∞fi

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·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· Û˘ÌÙÒÌ·Ù· ‹ Û ÂÚ›Ô‰Ô ‡ÊÂÛ˘ ‹ ·Ô-‰ÚÔÌ‹˜ Ù˘ ÎÏÈÓÈ΋˜ Û˘Ìو̷ÙÔÏÔÁ›·˜, ÂÍÂÙ¿ÛÙËÎ·Ó ‰Â›ÁÌ·-Ù· Ô‡ÚˆÓ Ù˘ ÚÒÙ˘ ÚˆÈÓ‹˜ Ô‡ÚËÛ˘. ™Â ÂÚÈÔÚÈṲ̂ÓÔ·ÚÈıÌfi ÂÚÈÙÒÛÂˆÓ (~2%) ÂÏ‹ÊıËÛ·Ó ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ ˘fiÂÏÂÁ¯fiÌÂÓ˜ Û˘Óı‹Î˜. ¶·ÚÂÏ‹ÊıËÛ·Ó Ô‡Ú· ·ÛıÂÓÒÓ 2-6ÒÚ˜ ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË Á‡̷ÙÔ˜ ‹ ÚˆÙ½Ó˘ (2 g/kg ‚¿-ÚÔ˘˜) ‹ ÁÏ˘Îfi˙˘ (1,7 g/kg ‚¿ÚÔ˘˜) ‹ ·Ú·ÙÂٷ̤Ó˘ ÓËÛÙ›-·˜, Ì ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· ÙÔ˘ ·ÛıÂÓÔ‡˜.∏ ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓ ¤ÁÈÓ Ì ÙËÓ ÙÂ-¯ÓÈ΋ GC-MS Î·È ÂÊ·ÚÌfiÛÙËÎÂ Ë ÎÏ·ÛÈ΋ ÌÂıÔ‰ÔÏÔÁ›· Ù˘˘ÁÚ‹˜ Âί‡ÏÈÛ˘ Ì ÔÚÁ·ÓÈÎÔ‡˜ ‰È·Ï‡Ù˜ Î·È Ë ¯ËÌÈ΋ ·Ú·-ÁÔÓÙÔÔ›ËÛ‹ ÙÔ˘˜ Û ÙÚÈÌÂı˘ÏÔÛ˘ÏÈÎÔ-ÂÓÒÛÂȘ(trimethylsilylation) (15). ∞ÍÈÔÏÔÁ‹ıËÎ·Ó Ù· ÔÚÁ·ÓÈο Ôͤ· ËÌÈ-ÔÛÔÙÈο ‚¿ÛÂÈ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙˆÓ Ô‡ÚˆÓ (mmol/mol ÎÚ·ÙÈ-Ó›Ó˘) Ì ÙË ¯Ú‹ÛË ÂÛˆÙÂÚÈÎÔ‡ ÚÔÙ‡Ô˘ Ô˘Û›·˜. ∏ ·Ó¿Ï˘ÛˤÁÈÓ Û ·Ó·Ï˘Ù‹ Ù‡Ô˘ Carlo-Elba 2000, Fison’s MD800, ÙÂ-¯ÓÈ΋ ¤Á¯˘Û˘ splitless, Ù‡Ô˜ ÈÔÓÈÛÌÔ‡ electron-impact ηȯڋÛË ÛÙ‹Ï˘ ¯ÚˆÌ·ÙÔÁÚ·Ê›·˜ Ù‡Ô˘ BP-1 ‹ BP-5. ™Â 122·ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈο ÎÏÈÓÈο ‹ ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ÔÚ-Á·ÓÈ΋˜ Ô͢Ԣڛ·˜ ‹ ·Ó¿ÚÎÂÈ·˜ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·-ÚÒÓ ÔͤˆÓ, ÂÍÂÙ¿ÛÙËΠÙÔ Ê¿ÛÌ· ÙˆÓ Û˘Ó‰Â‰ÂÌ¤ÓˆÓ ·Î˘ÏÔ-ηÚÓÈÙÈÓÒÓ (acyl-carnitine profile) ·fi ÛÙ·ÁfiÓ˜ ÍËÚÔ‡ ·›Ì·ÙԘ̠ÙË ÌÂıÔ‰ÔÏÔÁ›· (16) Tandem-MS (Û‡ÛÙËÌ· ‰‡Ô Ê·ÛÌ·ÙÔ-ÁÚ¿ÊˆÓ Ì·˙ÒÓ), ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÂȉÈο ÂÚÁ·ÛÙ‹ÚÈ· ÙÔ˘ Â͈-ÙÂÚÈÎÔ‡. ∏ ÙÂÏÈ΋ ÙÂÎÌËÚ›ˆÛË ÙÔ˘ ˘Â‡ı˘ÓÔ˘ ÂÓ‰ÔÁÂÓÔ‡˜ ÌÂÈ-ÔÓÂÎÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ¤ÁÈÓ Ì ÙË Ì¤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙË-Ù·˜ ÙˆÓ ÂÓ¯fiÌÂÓˆÓ ÂÓ˙‡ÌˆÓ ‹ Î·È ÙË ÁÔÓȉȷ΋ ·Ó¿Ï˘ÛË ÙˆÓ·ıÔÁfiÓˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ·fi ÂÍÂȉÈÎÂ˘Ì¤Ó· ÂÚÁ·ÛÙ‹ÚÈ· ÙÔ˘Â͈ÙÂÚÈÎÔ‡, Ì ·ÍÈfiÈÛÙ˜ ·Ó·Ï˘ÙÈΤ˜ Ù¯ÓÈΤ˜ (13). ÀÏÈÎfi Ù˘·Ó¿Ï˘Û˘ ‹Ù·Ó ·ÙÙ·Ú· ÙˆÓ ·ÛıÂÓÒÓ ·fi ‚ÈÔ„›· ‰¤ÚÌ·ÙÔ˜,‹·ÙÔ˜ ‹ ·ÙÙ·Ú· ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜.

∞ÔÙÂϤÛÌ·Ù· ∞fi ÙȘ ·Ó·Ï‡ÛÂȘ ‰È·ÈÛÙÒıËÎ·Ó ‰È·ÁÓˆÛÙÈΤ˜

‰È·Ù·Ú·¯¤˜ ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ Û 85 Û˘ÓÔÏÈ-

ο ·ÛıÂÓ›˜, Û 10 ÂÎ ÙˆÓ ÔÔ›ˆÓ, fï˜, Ë ‰È¿ÁÓˆ-ÛË Ù˘ ÓfiÛÔ˘ ›¯Â ‹‰Ë ÙÂı› ·fi ÚÔÁÂÓ¤ÛÙÂÚ˜·Ó·Ï‡ÛÂȘ ÂÚÁ·ÛÙËÚ›ˆÓ ÙÔ˘ Â͈ÙÂÚÈÎÔ‡ ÙËÓ ›‰È·¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô (¶›Ó·Î·˜ 2). ∂ȉÈÎfiÙÂÚ·, ‰È·È-ÛÙÒıËÎ·Ó Û 65 ·ÛıÂÓ›˜, 16 ‰È·ÊÔÚÂÙÈΤ˜ ÂÓ˙˘ÌÈ-Τ˜ ‹ ÚˆÙÂ˚ÓÈΤ˜ ·Ó¿ÚÎÂȘ, Ì ¯·Ú·ÎÙËÚÈÛÙÈ΋·¤ÎÎÚÈÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ (¶›Ó·Î·˜ 2, ÓÔÛ‹Ì·Ù·1-16). OÈ ·Ó·Ï‡ÛÂȘ ÙˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ ·›Ì·ÙÔ˜¤ÁÈÓ·Ó Û 25 ·fi ÙÔ˘˜ 65 ·ÛıÂÓ›˜ Î·È ¤‰ÂÈÍ·Ó Â›-Û˘ ·ıÔÏÔÁÈΤ˜ ‰È·ÁÓˆÛÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ (¶›Ó·-η˜ 2, ÓÔÛ‹Ì·Ù· 5-9, 13-15). ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ÂÎ-‰‹ÏˆÓ·Ó Û˘Ìو̷ÙÔÏÔÁ›· ÛÙ· Ï·›ÛÈ· ÙˆÓ ÎÏÈÓÈ-ÎÒÓ Ê·ÈÓÔÙ‡ˆÓ ÙˆÓ ·ÓÙ›ÛÙÔȯˆÓ ÓÔÛËÌ¿ÙˆÓ. ∏ ÂÓ-˙˘ÌÈ΋ ‹/Î·È Ë ÁÔÓȉȷ΋ Ù·˘ÙÔÔ›ËÛË ÙˆÓ ·Ó·Ú-ÎÂÈÒÓ Ù˘ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ¤ÁÈÓ Û ÙÔ˘Ï¿¯È-ÛÙÔÓ 46 ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ. ™Â fiÏÔ˘˜ ÙÔ˘˜·ÛıÂÓ›˜, Ë ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· ¤¯ÂÈ ÂȂ‚·Èˆı›Ì Ӥ˜ ·Ó·Ï‡ÛÂȘ. ™Ù· ÓÔÛ‹Ì·Ù· Ù˘ 2-L-˘‰ÚÔ͢-ÁÏÔ˘Ù·ÚÈ΋˜ Ô͢Ԣڛ·˜ Î·È Âı˘ÏÔÌ·ÏÔÓÈ΋˜ ÂÁÎÂ-Ê·ÏÔ¿ıÂÈ·˜, ÛÙ· ÔÔ›· ‰ÂÓ ¤¯ÂÈ Ù·˘ÙÔÔÈËı›˘Â‡ı˘ÓË ·Ó¿ÚÎÂÈ· ÂÓ˙‡ÌÔ˘, ÚˆÙ½Ó˘ ‹ ÁÔÓÈ-‰È·Î‹˜ ÌÂÙ¿ÏÏ·Í˘, Ë ÓfiÛÔ˜ ÂȂ‚·ÈÒıËΠ̠ÙËÓ·Ó¿Ï˘ÛË ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ Ô‡ÚˆÓ Î·È ·fi ¿ÏÏÔ ÂÍÂÈ-‰ÈÎÂ˘Ì¤ÓÔ ÂÚÁ·ÛÙ‹ÚÈÔ.

∏ ·Ó¿Ï˘ÛË Ô‡ÚˆÓ ·fi 14 ·ÛıÂÓ›˜ ·ÔÎ¿Ï˘„·‡ÍËÛË ÙÔ˘ Á·Ï·ÎÙÈÎÔ‡ ÔͤԘ Î·È ‰È·Ù·Ú·¯¤˜ ÛÙ·ÔÚÁ·ÓÈο Ôͤ· ÙÔ˘ ÙÚÈηڂÔ͢ÏÈÎÔ‡ ·ÎÏÔ˘, ¢ڋ-Ì·Ù· ÂÓ‰ÂÈÎÙÈο ÌÂÙ·‚ÔÏÈ΋˜ ‰È·Ù·Ú·¯‹˜ Ù˘ ÔÌ¿-‰·˜ ÙˆÓ ÂÓ˙˘ÌÈÎÒÓ ·Ó·ÚÎÂÈÒÓ Ù˘ Á·Ï·ÎÙÈ΋˜ÌÂÙ·‚ÔÏÈ΋˜ ÔͤˆÛ˘. ∏ ÂȉÈÎfiÙÂÚË ‰ÈÂÚ‡ÓËÛË Û‰›ÁÌ·Ù· ‚ÈÔ„›·˜ Ì˘fi˜ ‹ ‰¤ÚÌ·ÙÔ˜ ·˘ÙÒÓ ÙˆÓ·ÛıÂÓÒÓ, ÂȂ‚·›ˆÛÂ Î·È Ù·˘ÙÔÔ›ËÛÂ Û˘ÁÎÂÎÚÈ-̤ÓË ÂÓ˙˘ÌÈ΋ ·Ó¿ÚÎÂÈ· ÙˆÓ Û˘ÌÏÂÁÌ¿ÙˆÓ Ù˘·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ Û 9 ·ÛıÂÓ›˜ Î·È Ù˘ ˘-ÚÔÛÙ·Ê˘ÏÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘ Û 4 ·ÛıÂÓ›˜. ™Â

¶›Ó·Î·˜ 1. ∫ÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ·ÛıÂÓÒÓ Ô˘ ÂÍÂÙ¿ÛÙËÎ·Ó ÁÈ· ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·

¢È·Ù·Ú·¯¤˜ ÙÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ¢˘ÛÏÂÈÙÔ˘ÚÁ›Â˜ ÔÚÁ¿ÓˆÓ∞ÛıÂÓ›˜ 2240 (63,3%) ∞ÛıÂÓ›˜ 1299 (36,7%)

∞.1) ∂ΉËÏÒÛÂȘ ¯ÚfiÓÈ·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ 2086 °.1) ¶ÚÔÂÍ¿Ú¯Ô˘Û˜ ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜ 935 (26,4%)æ˘¯ÔÎÈÓËÙÈ΋ ηı˘ÛÙ¤ÚËÛË 914 ∏·ÙÔÌÂÁ·Ï›·/Ë·ÙÈ΋ ‚Ï¿‚Ë 78/95=173™·ÛÌÔ› 760 ª˘˚Îfi 73¶ÚÔ‚Ï‹Ì·Ù· ÔÌÈÏ›·˜ 67 ∞Ó·Ó¢ÛÙÈÎfi 51¢È·Ù·Ú·¯¤˜ Û˘ÌÂÚÈÊÔÚ¿˜/·˘ÙÈÛÌfi˜ 67/46=113 ª˘ÔηډÈÔ¿ıÂÈ·/ηډȷΤ˜ ·ÓˆÌ·Ï›Â˜ 56/24=80¡ÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË 93 ∞ÈÌÔÔÈËÙÈÎfi 62ª·ÎÚÔÎÂÊ·Ï›· 72 ∂Ó‰ÔÎÚÈÓÔÏÔÁÈÎfi 25ªÈÎÚÔÎÂÊ·Ï›· 45 ¡ÂÊÚ¿ 70À‰ÚÔΤʷÏÔ˜ 24 ¶ÂÙÈÎfi/ÏÔÈÌÒÍÂȘ 206∂ÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË 126 ¢¤ÚÌ·/ÙÚ›¯Â˜ 24∞Ù·Í›·/‰˘ÛÙÔÓ›· 128/18=146 ŸÚ·ÛË 61ÀÂÚÙÔÓ›·/ÙÚfiÌÔ˜ 64/21=85 ∞ÎÔ‹ 40ÀÔÙÔÓ›· 246 ™Ï‹Ó·˜ 36

∞.2) OÍ›· ÂÁÎÂÊ·ÏÔ¿ıÂÈ· 154 (4,3%) ¶¿ÁÎÚ·˜ 13∫ÒÌ·, Ï‹ı·ÚÁÔ˜ 86 OÛÙ¿ 21¢È·Ù·Ú·¯‹ ÂȤ‰Ô˘ Û˘Ó›‰ËÛ˘, ¿ÓÔȘ 68 °.2) ¢˘ÛÙÚÔÊ›·, ÛÙ·ÛÈÌfiÙËÙ· ‚¿ÚÔ˘˜ 309 (8,7%)

B) ¢˘ÛÌÔÚʛ˜ 55 °.3) ªÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜ 260 (7,3%)

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122

¤Ó·Ó ·ÛıÂÓ‹, Ô ÔÔ›Ô˜ ·Â‚›ˆÛÂ, Ô ¤ÏÂÁ¯Ô˜ ÛÙ·Ô‡Ú· ·ÔÎ¿Ï˘„ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ÙˆÓ Ô˘ÚÈÓÒÓ. ™Â 5 ·ÛıÂÓ›˜, Ë ·Ó¿Ï˘ÛË ÙˆÓ ·Î˘-ÏÔηÚÓÈÙÈÓÒÓ ¤‰ÂÈÍ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·, ÂÓ‰ÂÈ-ÎÙÈο ·Ó¿ÚÎÂÈ·˜ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓÔͤˆÓ ÛÙ· ÌÈÙÔ¯fiÓ‰ÚÈ·. ∞˘ÙÔ› ÔÈ ·ÛıÂÓ›˜, ›Û˘·ÚÔ˘Û›·Û·Ó ‰ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ· Î·È ÌÂȈ̤-ÓË Û˘ÁΤÓÙÚˆÛË Ù˘ ÂχıÂÚ˘ Î·È ÔÏÈ΋˜ ηÚÓÈÙ›-Ó˘ ÛÙÔ ·›Ì· (¶›Ó·Î·˜ 2). ¢ÂÓ ÂÍÂÙ¿ÛıËÎÂ, fï˜,ÂÚ·ÈÙ¤Úˆ Ë Èı·Ó¿ ˘Â‡ı˘ÓË ÂÓ˙˘ÌÈ΋ ·Ó¿Ú-ÎÂÈ·. ™Â ¿ÏÏÔ˘˜ 5 ·ÛıÂÓ›˜, Ë ·‡ÍËÛË ÙˆÓ ·Î˘ÏÔ-ηÚÓÈÙÈÓÒÓ ÙÔ˘ ·›Ì·ÙÔ˜ ‰ÂÓ ‰È¢ÎÚÈÓ›ÛÙËΠ̠Â-Ú·ÈÙ¤Úˆ ·Ó·Ï‡ÛÂȘ. ∂›Û˘, Ë ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·-ÓÈÎÒÓ ÔͤˆÓ ·Ó¤‰ÂÈÍ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ›‰Ô˘˜ ηÈ

Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Û 247·ÛıÂÓ›˜ (5,3% ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ) (¶›-ӷη˜ 3), ÛÙÔ˘˜ ÔÔ›Ô˘˜ Ô Â·Ó¤ÏÂÁ¯Ô˜ Î·È Ë ‰ÈÂ-Ú‡ÓËÛË Èı·Ó‹˜ ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ∫ª¡ ‰ÂÓÚÔ¯ÒÚËÛ ÂÚ·ÈÙ¤Úˆ.

OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÛÙȘ ηÙËÁÔڛ˜ ∞.1, µÎ·È °.2 ÛÙÔÓ ¶›Ó·Î· 1 ·Ó·Ê¤ÚÔÓÙ·È Û ̷ÎÚÔ¯Úfi-ÓÈ· ‰È¿ÚÎÂÈ· Ù˘ ÓfiÛÔ˘ (>6 Ì‹Ó˜). OÈ ·ÛıÂÓ›˜ ·˘-ÙÔ› ·ÔÙÂÏÔ‡Ó ¿Óˆ ·fi ÙÔ 60% ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË. ∏ ‰ÈÂÚ‡ÓËÛË Ô˘ ¤ÁÈÓ Û·˘Ù‹ ÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ ·ÔÎ¿Ï˘„ 27 ·ÛıÂ-Ó›˜ ·fi ÙÔ˘˜ 85 Ì ‰È·ÁÓˆÛÙÈ΋ ÔÚÁ·ÓÈ΋ Ô͢Ԣ-Ú›·. ™Ô‚·Úfi Ô͇ ÌÂÙ·‚ÔÏÈÎfi ÂÂÈÛfi‰ÈÔ, ÔÍ›· ÂÁÎÂ-Ê·ÏÔ¿ıÂÈ· ‹ ÔÍ›· ÔÚÁ·ÓÈ΋ ‚Ï¿‚Ë, ÂΉËÏÒÛÂȘ

¶›Ó·Î·˜ 2. ªÂÙ·‚ÔÏÈΤ˜ ·Ó¿ÚÎÂȘ ·ÛıÂÓÒÓ Ì ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·, ÔÈ ÔÔ›ÔÈ ‰È·ÁÓÒÛÙËÎ·Ó ÙËÓ ÂÚ›Ô‰Ô 1996-2001

¡fiÛËÌ· ∞ÛıÂÓ›˜ ∂Ȃ‚·›ˆÛË ∂Ó ˙ˆ‹ ∞‚›ˆÛ·Ó ∂Ó˙˘ÌÈ΋ °ÔÓȉȷΤ˜ ÓfiÛÔ˘ ·Ó¿ÚÎÂÈ· ÌÂÙ·ÏÏ¿ÍÂȘ

1. ∞ÏηÙÔÓÔ˘Ú›· 5 - 2 3 - -2. ÀÂÚ·Ì̈ÓÈ·ÈÌ›·, ÔÚÔÙÈ΋ Ô͢Ԣڛ· 10 - - - - -

O∆C deficiency (5+2*) 1 2 4 5 2ASS deficiency (1) - - 1 1 1LPI disorder (2) 2 4 0 - 4

3. MSUD 3 0 3 0 3 -4. T˘ÚÔÛÈÓ·ÈÌ›· (π) 1 1 1 1 1 -5·. MMA mut 7 - 2 2 4 -5‚. Adocbl(A) 0 1 1 - 1 -6. ¶ÚÔÈÔÓÈ΋ Ô͢Ԣڛ· 2+1** 1 1 2 3 -7. HMGlyase-deficiency 2 0 2 0 2 ™Â ÂͤÏÈÍË8. ‚-ÎÂÙÔıÈÔÏ¿ÛË 1 0 1 0 1 -9. °ÏÔ˘Ù·ÚÈ΋ Ô͢-(I) 4 2 6 0 3 -10. Canavan disease 2 0 2 0 2 211. SSADH-deficiency 6 0 5 0 5 512. L-2-OH-GA 3 1 2 0 - -13. MADD 1 0 0 1 1 014. MCAD 6 1 6 0 0 715. EPEMA syndrome 1 0 1 0 ∂ÚÂ˘Ó¿Ù·È -¢È·Ù·Ú·¯¤˜, DCA+AC+ηÚÓÈÙ›Ó˘ 5 0 - - - -™‡ÓÔÏÔ 59 10°·Ï·ÎÙÈ΋ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË 14 0 - - 12 -16. DPD deficiency 1 0 1 0 1 1¢È·Ù·Ú·¯¤˜ Ô˘ÚÈÓÒÓ 1 0 - 1 - -™‡ÓÔÏÔ 75 10 42 15 45 21

O∆C: ÔÚÓ˘ı˘ÏÔηڂ·ÌÈÏÔ-ÙÚ·ÓÛÊÂÚ¿ÛË ASS: Û˘ÓıÂÙ¿ÛË ·ÚÁÈÓÈÓÔËÏÂÎÙÚÈÎÔ‡ ÔͤԘ LPI: ‰˘Û·ÓÂÍ›· Ù˘ Ï˘Û›Ó˘ MSUD: ÓfiÛÔ˜ Ì ÔÛÌ‹ ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘ ÙˆÓ Ô‡ÚˆÓ MMA mut: ÌÂı˘ÏÔÌË(·)ÏÔÓÈ΋ Ô͢Ԣڛ· ·Ó¿ÚÎÂÈ· ÌÔ˘Ù¿Û˘ Adocbl(A): ·Ó¿ÚÎÂÈ· ·‰ÂÓÔÛ˘ÏÔÎÔ‚·Ï·Ì›Ó˘ ∞ HMGlyase: 3-˘‰Úfi͢-3-ÌÂı˘ÏÔ-ÁÏÔ˘Ù·ÚÈ΋˜ Ï˘¿Û˘ SSADH: ‰Â¸‰ÚÔÁÂÓ¿ÛË Ù˘ ËÌȷω¸‰Ë˜ ÙÔ˘ ËÏÂÎÙÚÈÎÔ‡ Ôͤˆ˜ L-2-OH-GA: L-2-˘‰Úfi͢-ÁÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ· DPD deficiency: ·Ó¿ÚÎÂÈ· ‰Â¸‰ÚÔÁÂÓ¿Û˘ ÙˆÓ ‰È¸‰ÚÔ˘ÚÈÌȉÈÓÒÓ MADD: ·Ó¿ÚÎÂÈ· ÔÏÏ·ÏÒÓ ‰Â¸‰ÚÔÁÂÓ·ÛÒÓ MCAD: ·Ó¿ÚÎÂÈ· ‰Â¸‰ÚÔÁÂÓ¿Û˘ ÏÈ·ÚÒÓ ÔͤˆÓ ̤Û˘ ·Ï‡ÛÔ˘ EPEMA syndrÔme: Û‡Ó‰ÚÔÌÔ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜-Âı˘ÏÔÌ·ÏÔÓÈ΋˜ Ô͢Ԣڛ·˜ DCA: ‰ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ· AC: ·Î˘ÏÔηÚÓÈÙ›Ó˜ * ÂÙÂÚÔ˙˘ÁÒÙ˜ ÌËÙ¤Ú˜ Ì ıÂÙÈο Â˘Ú‹Ì·Ù· Ù˘ ·Ó¿ÚÎÂÈ·˜ ** ·ÛıÂÓ‹˜ Ì ۷ʤ˜ Ê¿ÛÌ· ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Î·È ÎÏÈÓÈÎfi ÂÂÈÛfi‰ÈÔ, ¯ˆÚ›˜ ÙÂÏÈ΋ ÂȂ‚·›ˆÛË

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Ô˘ ΢ڛˆ˜ ·Ó·Ê¤ÚÔÓÙ·È ÛÙȘ ηÙËÁÔڛ˜ ∞.2, °.1,°.3, ·ÚÔ˘Û›·Û·Ó 908 ·ÛıÂÓ›˜ (25% ÙˆÓ ·Ó·ÊÂ-ÚÔ̤ӈÓ). ∞fi ÙË ‰ÈÂÚ‡ÓËÛË ·˘Ù‹˜ Ù˘ ÔÌ¿‰·˜ÂΉËÏÒÛˆÓ, ‰È·ÈÛÙÒıËΠ‰È·ÁÓˆÛÙÈ΋ ÔÚÁ·ÓÈ΋Ô͢Ԣڛ· Û 51 ·ÛıÂÓ›˜. ∏ ‰È¿ÎÚÈÛË Î·È Ù·ÍÈÓfiÌË-ÛË ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·ÚÔ˘Û›·˙·Ó ‰È·Ï›ԢÛ˜ ‹‹È˜ ÂΉËÏÒÛÂȘ, ‰ÂÓ ¤ÁÈÓ ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË.ŸÌˆ˜, ÔÈ 7 ·fi ÙÔ˘˜ 85 ·ÛıÂÓ›˜ Ì ‰È·ÁÓˆÛÙÈ΋ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· ‰ÈÂÚ¢ӋıËηÓ, ‰ÈfiÙÈ ·ÚÔ˘-Û›·˙·Ó ‰È·ÏÂ›Ô˘Û· Û˘Ìو̷ÙÔÏÔÁ›· ÂΉËÏÒÛÂ-ˆÓ. π‰È·›ÙÂÚË ·Í›· ¤¯Ô˘Ó Ù· ÛÙÔȯ›· Ù˘ ÔÚ›·˜ÙˆÓ ·ÛıÂÓÒÓ ÌÂÙ¿ ÙË ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘. ∞Â-‚›ˆÛ·Ó 15 ·ÛıÂÓ›˜, 6 ÂÎ ÙˆÓ ÔÔ›ˆÓ ηٿ ÙËÓ Â-Ú›Ô‰Ô ÙÔ˘ ÚÒÙÔ˘ ÂÂÈÛÔ‰›Ô˘ Ù˘ ÓfiÛÔ˘. OÈ 23·fi ÙÔ˘˜ 42 ˙ÒÓÙ˜ ·ÛıÂÓ›˜ Ì ÁÓˆÛÙ‹ ÎÏÈÓÈ΋ Ô-Ú›· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÔ‚·Ú‹ ÓÔÛËÚfiÙËÙ·.

™˘˙‹ÙËÛË O ·ÚÈıÌfi˜ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÈÂÚ¢ӋıËÎ·Ó ÁÈ·

Èı·Ó‹ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·, ·ÓÙÈÛÙÔȯ› ÛÙÔ 0,83%ÂÚ›Ô˘ ÙˆÓ ÁÂÓÓ‹ÛÂˆÓ ·˘Ù‹˜ Ù˘ ÂÚÈfi‰Ô˘ ÛÙ˯ÒÚ·. ¢Â‰Ô̤ÓÔ˘ fiÙÈ Ë ‰ÈÂÚ‡ÓËÛË ÁÈ· Èı·Ó‹ ÔÚ-Á·ÓÈ΋ Ô͢Ԣڛ· Ú·ÁÌ·ÙÔÔÈ‹ıËΠϋڈ˜ ÌfiÓÔ·fi ÙË Û˘ÁÎÂÎÚÈ̤ÓË ÔÌ¿‰· ÛÙËÓ ∂ÏÏ¿‰·, ÙÔ Ì¤ÁÂ-ıÔ˜ ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ Â›Ó·È ÂÓ‰ÂÈÎÙÈÎfi ÁÈ· ÙËÓ ÂÍ·-ÁˆÁ‹ ¯Ú‹ÛÈÌˆÓ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ. ŒÙÛÈ, ÔÈ ·Ó·ÊÂ-ÚfiÌÂÓ˜ ‰ÈÂÚ¢ӋÛÂȘ ˘ÔÏ›ÔÓÙ·È ÙÔ˘ ÔÛÔÛÙÔ‡ÙˆÓ ·ÛıÂÓÒÓ Ì ÎÏËÚÔÓÔÌÈο ÓÔÛ‹Ì·Ù· Ô˘ ÔÊ›-ÏÔÓÙ·È Û ÌÔÓÔÁÔÓȉȷΤ˜ ·Ó¿ÚÎÂȘ (1% ÙˆÓÁÂÓÓ‹ÛˆÓ) (2). ÕÏψÛÙÂ, ÔÏÏÔ› ·ÛıÂÓ›˜ Ì ∫ª¡,·ÏÏ¿ Î·È ¿Û¯ÔÓÙ˜ ·fi ¿ÏϘ ηÙËÁÔڛ˜ ÓÔÛË-Ì¿ÙˆÓ, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÓ‰ÂÈÎÙÈΤ˜ ÎÏÈÓÈΤ˜ ÂΉËÏÒ-ÛÂȘ Ô˘ ÂÈ‚¿ÏÏÔ˘Ó ÙË ‰ÈÂÚ‡ÓËÛË Èı·Ó‹˜ ÔÚÁ·-ÓÈ΋˜ Ô͢Ԣڛ·˜. ∂›Û˘, ÂÎÙÈÌ¿Ù·È fiÙÈ ÛÙËÓ ·-

ÚÔ‡Û· ÌÂϤÙË, ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÈÂÚ¢ӋıËÎ·Ó ÌÂÂΉËÏÒÛÂȘ Ôͤˆ˜ ¿Û¯ÔÓÙÔ˜ ·ÔÙÂÏÔ‡Ó ÌÈÎÚfiÔÛÔÛÙfi Û¯ÂÙÈο Ì ÙÔ˘˜ ¯ÚfiÓÈ·˜ ‰È·‰ÚÔÌ‹˜ ¿-Û¯ÔÓÙ˜. ∂ÈϤÔÓ, ·fi ÙËÓ Î·ıËÌÂÚÈÓ‹ ÂÌÂÈÚ›·‰È·ÈÛÙÒÓÔ˘Ì fiÙÈ Ô ¤ÏÂÁ¯Ô˜ Èı·Ó‹˜ ÔÚÁ·ÓÈ΋˜Ô͢Ԣڛ·˜ Û Ôͤˆ˜ ¿Û¯ÔÓÙ˜ ·ÛıÂÓ›˜ ‰ÂÓ Ù›ıÂ-Ù·È ¿ÓÙ· ÛÙË ‰È·ÊÔÚÈ΋ ‰È·ÁÓˆÛÙÈ΋ ÛΤ„Ë ÙˆÓ·È‰È¿ÙÚˆÓ, fiˆ˜ ·Ó·Ê¤ÚÂÙ·È Î·È ‰ÈÂıÓÒ˜ (6). ∞Ó·-ʤÚıËΠfiÙÈ ÙÔ 9,31% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÂÍÂÙ·Ûı¤-ÓÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó ÓÂÔÁÓÈ΋˜ ËÏÈΛ·˜, Û 11 ÂÎ ÙˆÓÔÔ›ˆÓ Ù¤ıËÎÂ Ë ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘. ∆Ô ÔÛÔÛÙfi·˘Ùfi ÙˆÓ ·ÛıÂÓÒÓ ·Ê›ÛÙ·Ù·È ÛËÌ·ÓÙÈο ÙˆÓ ·ÛıÂ-ÓÒÓ Ì ∫ª¡, ÔÈ ÔÔ›ÔÈ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÙË ÓÂÔÁÓÈ΋ËÏÈΛ· ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›· (ÙÔ ÔÛÔÛÙfi ÊÙ¿-ÓÂÈ ÛÙÔ 25% ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ∫ª¡). ∂ÎÙfi˜ ÙÔ˘˘Ô‰ËÏÔ‡ÌÂÓÔ˘ ¯·ÌËÏÔ‡ ÔÛÔÛÙÔ‡ ÂÍÂÙ·˙fiÌÂÓˆÓÁÈ· Èı·Ó‹ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·, ÔÈ ÙÂı›Û˜ ‰È·ÁÓÒ-ÛÂȘ Â›Ó·È ÔÛÔÛÙÈ·›· ÏÈÁfiÙÂÚ˜ ·fi ÙȘ ‰È·ÁÓÒÛÂȘ¿ÏÏˆÓ Â˘Úˆ·˚ÎÒÓ ÂÚÁ·ÛÙËÚ›ˆÓ (17). ™˘ÁÎÂÎÚÈ̤-Ó·, ÔÈ ‰È·ÁÓÒÛÂȘ ÙˆÓ 85 ÂÚÈÙÒÛÂˆÓ ∫ª¡ ·ÔÙÂ-ÏÔ‡Ó ÙÔ 1,69% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ·ÛıÂÓÒÓ.

™¯ÂÙÈο Ì ÙȘ ÙÂı›Û˜ ‰È·ÁÓÒÛÂȘ (¶›Ó·Î·˜ 2,ÓÔÛ‹Ì·Ù· 1-15), ÔÈ ÔÌ¿‰Â˜ ÙˆÓ ·Ó·ÚÎÂÈÒÓ ÙÔ˘ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, ·ÌÈÓÔ-Ô͢Ô-¿ıÂÈ·˜ ‹ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜, ‰È·-ÈÛÙÒıËÎ·Ó Û 69 ·ÛıÂÓ›˜. ∏ ·ıÚÔÈÛÙÈ΋ Û˘¯Ófi-ÙËÙ· ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ·˘Ù¤˜ ÙȘ ·Ó¿ÚÎÂȘÊÙ¿ÓÂÈ ÙË 1:8696 ÁÂÓÓ‹ÛÂȘ (Ì ‚¿ÛË ÙȘ 100.000ÂÚ›Ô˘ ÁÂÓÓ‹ÛÂȘ ÂÙËÛ›ˆ˜ ÛÙË ¯ÒÚ·).

∂ȉÈÎfiÙÂÚ·, ÛËÌ·ÓÙÈ΋, ·ÏÏ¿ ÏÈÁfiÙÂÚÔ ·fi ÙȘ·Ó·ÊÔÚ¤˜ ÛÂ Â˘Úˆ·˚Τ˜ ¯ÒÚ˜ Î·È ÛÙȘ ∏¶∞ (18),·Ó·‰ÂÈÎÓ‡ÂÙ·È Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÓÔÛËÌ¿ÙˆÓ Ù˘ ÌÂ-ı˘ÏÔÌ·ÏÔÓÈ΋˜ Î·È Ù˘ ÚÔÈÔÓÈ΋˜ Ô͢Ԣڛ·˜ ηÈ

¶›Ó·Î·˜ 3. ∂Ӊ›ÍÂȘ Èı·Ó‹˜ ÌÂÙ·‚ÔÏÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ·fi ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ·ÛıÂÓÒÓ

∞ÍÈÔÏfiÁËÛË Â˘ÚËÌ¿ÙˆÓ Ù˘ ·Ó¿Ï˘Û˘ ∞ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈΤ˜ ‰È·Ù·Ú·¯¤˜

1. ªÂı˘ÏÔÌ·ÏÔÓÈ΋ Ô͢Ԣڛ· 152. ¢ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ· ‚-ÔÍ›‰ˆÛ˘ ÏÈ·ÚÒÓ ÔͤˆÓ 583. OÚÔÙÈÎfi Ô͇, Èı·Ó‹˜ ·Ó¿ÚÎÂÈ·˜ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜ 104·. °·Ï·ÎÙÈ΋ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË: Á·Ï·ÎÙÈ΋ Ô͢Ԣڛ· 334‚. ∂Ó‰ÂÈÎÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ 414Á. ¢È·Ù·Ú·¯¤˜ ÙÔ˘ ·ÎÏÔ˘ ÙˆÓ ÙÚÈηڂÔ͢ÏÈÎÒÓ ÔͤˆÓ 195. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ÁÏÔ˘Ù·ÚÈ΋˜ Ô͢Ԣڛ·˜ Ù‡Ô˘ π 36. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ Ù˘ÚÔÛÈÓ·ÈÌ›·˜ Ù‡Ô˘ ππ 37. ∞‡ÍËÛË ˘‰ÚÔ͢-‰È·ÎÏ·‰ˆÙÈÎÒÓ ÔͤˆÓ ÂÓ‰ÂÈÎÙÈ΋ Èı·Ó‹˜

ÓfiÛÔ˘ ÔÛÌ‹˜ Ô‡ÚˆÓ Û·Ó ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘ 58. 3-ÌÂı˘ÏÔ-ÁÏÔ˘Ù·ÎÔÓÈ΋ Ô͢Ԣڛ· 79. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ‰È·Ù·Ú·¯‹˜ ÙˆÓ Ó¢Úԉȷ‚È‚·ÛÙÒÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ÓÙÔ·Ì›Ó˘ 210. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ Èı·Ó‹˜ ˘ÂÚÔÍ·ÏÔ˘Ú›·˜ Ù‡Ô˘ π 311. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ‰È·Ù·Ú·¯ÒÓ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ˘ÂÚÔÍ˘ÛˆÌ¿ÙˆÓ 612·. ∞˘ÍË̤ÓË ·¤ÎÎÚÈÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÌË ÂȉÈÎÔ‡ ÚÔÊ›Ï ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ 2412‚. ªÂÌÔӈ̤ÓË ·‡ÍËÛË ÙÈÁÏ˘ÏÔÁÏ˘Î›Ó˘ 1012Á. ªÂÌÔӈ̤ÓË ·‡ÍËÛË 3-˘‰ÚÔ͢-ÈÛÔ‚·ÏÂÚÈÎÔ‡ ÔͤԘ 8

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·123

ÙˆÓ ·Ó·ÚÎÂÈÒÓ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜. ∞˘ÍË̤-ÓË ÂÌÊ·Ó›˙ÂÙ·È Ë Û˘¯ÓfiÙËÙ· ÓÔÛËÌ¿ÙˆÓ fiˆ˜ Ë 4-˘‰ÚÔ͢-‚Ô˘Ù˘ÚÈ΋ Ô͢Ԣڛ· (¤¯Ô˘Ó ÂÚÈÁÚ·Ê›150 ÂÚÈÛÙ·ÙÈο) (19). O ˘ÔÏÔÁÈÛÌfi˜ Ù˘ Û˘¯Ófi-ÙËÙ·˜ Ù˘ ·ÏηÙÔÓÔ˘Ú›·˜ Â›Ó·È ‰˘Û¯ÂÚ‹˜, ÂÍ·È-Ù›·˜ Ù˘ ηı˘ÛÙ¤ÚËÛ˘ ÙˆÓ ÂΉËÏÒÛÂˆÓ Î·È Ù˘‹È·˜ ÎÏÈÓÈ΋˜ Û˘Ìو̷ÙÔÏÔÁ›·˜. ÕÏψÛÙ ÛÙËÌÂϤÙË Ì·˜, 4/5 ·ÛıÂÓ›˜ ‹Ù·Ó ÂÓ‹ÏÈΘ. ∏ ·Ó¿Ú-ÎÂÈ· Ù˘ ·Ê˘‰ÚÔÁÔÓ¿Û˘ ̤Û˘ ·Ï‡ÛÔ˘ ÏÈ·ÚÒÓÔͤˆÓ (MCAD) ·Ó·Ê¤ÚÂÙ·È Û 7 ·ÛıÂÓ›˜, ÔÈ 3 ·fiÙÔ˘˜ ÔÔ›Ô˘˜ ‹Ù·Ó ÙÛÈÁÁ¿ÓÈ΢ ηٷÁˆÁ‹˜. ∂›Ó·ÈÁÓˆÛÙfi fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì Èı·Ó‹ ÂÓ˙˘ÌÈ΋ ·Ó¿Ú-ÎÂÈ· Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ (Û˘Ó‹-ıˆ˜ ·ÛıÂÓ›˜ Ì ÂΉËÏÒÛÂȘ ÎÚ›ÛÂˆÓ ˘ÔÁÏ˘Î·È-Ì›·˜, Ì˘˚Τ˜ ‰È·Ù·Ú·¯¤˜, ÔÍ›· ÂÁÎÂÊ·ÏÔ¿ıÂÈ·ÌÂÙ¿ ·fi Ïԛ̈ÍË, Ì˘ÔηډÈÔ¿ıÂÈ·), ‰È·ÁÓˆÛÙÈο·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È, ÂÎÙfi˜ ·fi ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ÔÚ-Á·ÓÈÎÒÓ ÔͤˆÓ ÛÙ· Ô‡Ú·, Î·È Ì ̤ÙÚËÛË ÙˆÓ ·Î˘-ÏÔηÚÓÈÙÈÓÒÓ ÛÙÔ ·›Ì· (20). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË,ÌÈÎÚfi ÌfiÓÔ ÙÌ‹Ì· ·ÛıÂÓÒÓ Ì ·˘Ù¤˜ ÙȘ ÎÏÈÓÈΤ˜ÂӉ›ÍÂȘ ‰ÈÂÚ¢ӋıËΠϋڈ˜ Î·È Ù· Û¯ÂÙÈο ¢-Ú‹Ì·Ù· ‰ÂÓ ÂÈÙÚ¤Ô˘Ó Û·Ê›˜ ÂӉ›ÍÂȘ ÁÈ· ÙË Û˘-¯ÓfiÙËÙ¿ ÙÔ˘˜ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi. ŸÌˆ˜, Ù·Â˘Ú‹Ì·Ù· ·˘Ù¿, fiˆ˜ Î·È ¿ÏϘ ¢ڇÙÂÚ˜ ÏËı˘-ÛÌȷΤ˜ ÌÂϤÙ˜ ÛÙËÓ ∂˘ÚÒË (21), ‰Â›¯ÓÔ˘Ó fiÙÈ ËÛ˘¯ÓfiÙËÙ· ÙˆÓ ·Ó·ÚÎÂÈÒÓ ·˘ÙÒÓ Ú¤ÂÈ Ó· ›ӷÈÛËÌ·ÓÙÈ΋. ∂Ó‰ÂÈÎÙÈο ·Ó·Ê¤ÚÂÙ·È (22) fiÙÈ ÙÔ 1-3%ÙˆÓ ·‰È¢ÎÚ›ÓÈÛÙˆÓ ı·Ó¿ÙˆÓ ÛÙË ‚ÚÂÊÈ΋ Î·È ·È-‰È΋ ËÏÈΛ· ÛÙ· ÓÔÛÔÎÔÌ›· (SIDS) Û¯ÂÙ›˙ÂÙ·È Ì ÂÓ-˙˘ÌÈΤ˜ ·Ó¿ÚÎÂȘ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓÔͤˆÓ. ∂Ó·ÏÏ·ÎÙÈο, ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô › ˘Ô„›·˜·˘ÙÒÓ ÙˆÓ ·Ó·ÚÎÂÈÒÓ, Û˘ÓÈÛÙ¿Ù·È Ë ÂÊ·ÚÌÔÁ‹ÂȉÈÎÒÓ ‰ÔÎÈÌ·ÛÈÒÓ ÊfiÚÙÈÛ˘ ÙˆÓ ·ÛıÂÓÒÓ, Ì Ԣ-ۛ˜ fiˆ˜ ËÏȤϷÈÔ (sunflower oil, 1,5 g/kg ‚¿-ÚÔ˘˜), 3-Ê·ÈÓ˘ÏÔÚÔÈÔÓÈÎÔ‡ ÔͤԘ (10-25 mg/kg‚¿ÚÔ˘˜), Ë ¯ÔÚ‹ÁËÛË Î·ÚÓÈÙ›Ó˘ (100 mg/kg) ‹ ·-Ú·ÙÂٷ̤Ó˘ ÓËÛÙ›·˜ (8-24 ÒÚ˜), ·Ó¿ÏÔÁ· Ì ÙËÓËÏÈΛ· Î·È ÙËÓ ·ÓÙÔ¯‹ ÙÔ˘ ·ÛıÂÓÔ‡˜, ÚÈÓ ·fi ÙËÏ‹„Ë ÙˆÓ Ô‡ÚˆÓ. ∏ ‰ÔÎÈÌ·Û›· Ù˘ ·Ú·ÙÂٷ̤Ó˘ÓËÛÙ›·˜ Û ·˘Ù‹ ÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ ÌÔÚ›ӷ ˘ÚÔ‰ÔÙ‹ÛÂÈ ÂÈΛӉ˘Ó˜ ÂΉËÏÒÛÂȘ ÁÈ· ÙË ˙ˆ‹ÙÔ˘ ·ÛıÂÓÔ‡˜ Î·È ‰ÂÓ ·Ó·‰ÂÈÎÓ‡ÂÈ ¿ÓÙ· ÙȘ ÂÓ‰ÂÈ-ÎÙÈΤ˜ ÌÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ÓfiÛÔ˘. ∏ ‰ÈÂ-Ú‡ÓËÛË ·ÛıÂÓÒÓ Ì ˘ÔÁÏ˘Î·ÈÌ›· ‹ Ì ÎÏÈÓÈΤ˜ÂΉËÏÒÛÂȘ ÂÓÂÚÁÂȷ΋˜ ·Ó¿ÚÎÂÈ·˜ Ì ‹ ¯ˆÚ›˜ÂÁÎÂÊ·ÏÔ¿ıÂÈ·, Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÈ Î·È ÙËÓ ÔÌ¿‰·ÙˆÓ ·Ó·ÚÎÂÈÒÓ Ù˘ Á·Ï·ÎÙÈ΋˜ ÌÂÙ·‚ÔÏÈ΋˜ Ôͤ-ˆÛ˘. ¶ÚÈÓ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙˆÓ ÂȉÈÎÒÓ ‚ÈÔ¯ËÌÈÎÒÓÎ·È ÈÛÙÔ¯ËÌÈÎÒÓ ÌÂıfi‰ˆÓ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ Ù˘ ÏÂÈ-ÙÔ˘ÚÁÈÎfiÙËÙ·˜ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ ÙˆÓ ÌÈ-ÙÔ¯ÔÓ‰Ú›ˆÓ Î·È ÙˆÓ ÂÓ˙‡ÌˆÓ Ù˘ ÁÏ˘ÎÔÓÂÔÁ¤ÓÂÛ˘,ÔÈ Ôԛ˜ Ù·˘ÙÔÔÈÔ‡Ó ÙËÓ ÂӉ¯fiÌÂÓË ÂÓ˙˘ÌÈ΋·Ó¿ÚÎÂÈ·, ‰È·ÁÓˆÛÙÈο ·ÍÈÔÏÔÁÔ‡ÓÙ·È Ù· ¢ڋ-

Ì·Ù· ·‰ÚÒÓ ‚ÈÔ¯ËÌÈÎÒÓ ‰ÔÎÈÌ·ÛÈÒÓ (23). ¶ÚÔÛ‰ÈÔ-Ú›˙ÂÙ·È ÙÔ Á·Ï·ÎÙÈÎfi Î·È ˘ÚÔÛÙ·Ê˘ÏÈÎfi Ô͇ ÛÙÔ·›Ì· Î·È ÙÔ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi Î·È Û˘ÌÏËÚˆ-Ì·ÙÈο ·ÍÈÔÏÔÁÂ›Ù·È Ë Ì¤ÙÚËÛË ÙÔ˘ ‚-˘‰ÚÔ͢-‚Ô˘-Ù˘ÚÈÎÔ‡ Î·È ÙÔ˘ ·ÎÂÙÔÍÈÎÔ‡ ÔͤԘ, ÛÙÔ ·›Ì· ‹ ηÈÙ· Ô‡Ú·. ™˘¯Ó¿, ÂÊ·ÚÌfi˙ÔÓÙ·È ÏÂÈÙÔ˘ÚÁÈΤ˜ ‰ÔÎÈ-̷ۛ˜ Ì ÙË ¯ÔÚ‹ÁËÛË Ô˘ÛÈÒÓ fiˆ˜ Ë ÁÏ˘Îfi˙Ë(1,7 g/kg ‚¿ÚÔ˘˜) ‹ Ë ·Ï·Ó›ÓË ‹ Á‡̷ÙÔ˜ ÏÔ‡ÛÈ-Ô˘ Û ˘‰·Ù¿ÓıڷΘ ÚÈÓ ÙȘ ÌÂÙÚ‹ÛÂȘ ·˘ÙÒÓ ÙˆÓÔ˘ÛÈÒÓ (24). OÈ Ù¯ÓÈΤ˜ ·˘Ù¤˜ ÂÊ·ÚÌfi˙ÔÓÙ·È Î·È Û·ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈο ÎÏÈÓÈο ÛÙÔȯ›·, fiˆ˜ ÛÂÂÂÈÛfi‰È· ΢ÎÏÔÙÂÚÒÓ Â̤وÓ, Û ÎÂÊ·Ï·ÏÁ›Â˜, ÛÂÔÍ›· ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ÌÂÙ¿ ·fi Ïԛ̈ÍË, ·Ú¿ÙËÓ ·Ô˘Û›· ¿ÏÏˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ.Œ¯Ô˘Ó ÂÊ·ÚÌÔÛÙ› ·Ó¿ÏÔÁ˜ ‰ÔÎÈ̷ۛ˜ Û 50 Â-Ú›Ô˘ ·ÛıÂÓ›˜, Ì ıÂÙÈο ÂÓ‰ÂÈÎÙÈο ·ÔÙÂϤÛÌ·-Ù· ·‡ÍËÛ˘ ÙÔ˘ Á·Ï·ÎÙÈÎÔ‡ ÔͤԘ ÛÙÔ ·›Ì·(>30%) Î·È ÂÓ‰ÂÈÎÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÎÂÙÔÓÈÎÒÓÛˆÌ¿ÙˆÓ ÛÙÔ ·›Ì· ‹ Î·È Ù· Ô‡Ú·. ∏ ‰È¿ÎÚÈÛË ÙˆÓ·ÈÙ›ˆÓ Ù˘ Á·Ï·ÎÙÈ΋˜ ÔͤˆÛ˘, ÌÂٷ͇ ÌÂÙ·‚ÔÏÈ-΋˜ ÂÓ˙˘ÌÈ΋˜ ÚˆÙÔÁÂÓÔ‡˜ ‹ ‰Â˘ÙÂÚÔÁÂÓÔ‡˜ ‹ÂÍ·ÈÙ›·˜ Û˘ÓıËÎÒÓ ˘ÔÍ·ÈÌ›·˜ ‹ ·ÓÔÍ·ÈÌ›·˜ ‹ ‰˘-ÛÏÂÈÙÔ˘ÚÁ›·˜ ˙ˆÙÈÎÒÓ ÔÚÁ¿ÓˆÓ, Â›Ó·È ·Ó·Áη›·ÚÈÓ ÙË Û˘Ó¤¯ÈÛË ÙÔ˘ ÂÚ·ÈÙ¤Úˆ ÂȉÈÎfiÙÂÚÔ˘ ÂϤÁ-¯Ô˘. ∞fi Ù· ÛÙÔȯ›· ÙˆÓ ¶ÈÓ¿ÎˆÓ 2 Î·È 3 Ê·›ÓÂÙ·ÈfiÙÈ Ë ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓÛ˘Ì‚¿ÏÏÂÈ, ÂÈÚfiÛıÂÙ· Ì ٷ ·ÓˆÙ¤Úˆ, ÛÙË ‰È·-ÁÓˆÛÙÈ΋ ÚÔÛ¤ÁÁÈÛË ·˘ÙÒÓ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Î·È‰Â›¯ÓÂÈ fiÙÈ Ô ·ÚÈıÌfi˜ ·˘Ù‹˜ Ù˘ ÔÌ¿‰·˜ ÙˆÓ ·ÓÂ-·ÚÎÂÈÒÓ Ú¤ÂÈ Ó· Â›Ó·È ÛËÌ·ÓÙÈÎfi˜ ÛÙËÓ ∂ÏÏ¿‰·.OÈ ÂÓ˙˘ÌÈΤ˜ ·Ó¿ÚÎÂȘ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜Ì ˘Ô„›· ÚÔËÁËı¤ÓÙÔ˜ ÂÂÈÛÔ‰›Ô˘ ÂÁÎÂÊ·ÏÔ¿-ıÂÈ·˜ ·fi ˘ÂÚ·Ì̈ÓÈ·ÈÌ›· ‹ ÔÈ ı‹ÏÂȘ Î·È ÌËÙ¤Ú˜ÂÙÂÚÔ˙˘ÁÒÙ˜ O∆C, ‰ÈÂÚ¢ÓÒÓÙ·È ÌÂÙ¿ ·fi ÙË Ï‹-„Ë Á‡̷ÙÔ˜ ÏÔ‡ÛÈÔ˘ Û ڈÙ½Ó˜ (2 g/kg ‚¿-ÚÔ˘˜) ‹ ÙË Ï‹„Ë ·ÏÏÔÔ˘ÚÈÓfiÏ˘ Î·È ÙË Ì¤ÙÚËÛËÙ˘ ·‡ÍËÛ˘ ÙÔ˘ ÔÚÔÙÈÎÔ‡ ÔͤԘ Î·È Ù˘ ԢڷΛ-Ï˘ ÛÙ· Ô‡Ú· Î·È Ù˘ ·Ì̈ӛ·˜ ÛÙÔ ·›Ì· (25). ¢È·-ÈÛÙÒıËΠ۠‰‡Ô ÌËÙ¤Ú˜ ·ÛıÂÓÒÓ O∆C (¶›Ó·Î·˜2), Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ ‰ÔÎÈÌ·Û›·˜ ÊfiÚÙÈÛ˘ Ì·ÏÏÔÔ˘ÚÈÓfiÏË, ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÔÚÔÙÈ-ÎÔ‡ ÔͤԘ ÛÙ· Ô‡Ú·. ªÂ ·ÚfiÌÔȘ ‰ÔÎÈ̷ۛ˜ÂϤÁ¯ÂÙ·È Ë ·Ó¿ÚÎÂÈ· ÙÔ˘ ηٷ‚ÔÏÈÛÌÔ‡ ÙˆÓ ·ÌÈ-ÓÔͤˆÓ. ™˘Ó‹ıˆ˜, ÌÂÙ¿ ·fi Ï‹„Ë ÚˆÙÂ˚ÓÒÓ ‹ ÂÈ-‰ÈÎÒÓ ·ÌÈÓÔͤˆÓ (fiˆ˜ Ï¢ΛÓË, ÈÛÔÏ¢ΛÓË, Ê·ÈÓ˘-Ï·Ï·Ó›ÓË, ÌÂıÂÈÔÓ›ÓË) ÚÔÛ‰ÈÔÚ›˙ÔÓÙ·È ·ÓÙ›ÛÙÔȯ··ÌÈÓÔͤ· Î·È ÔÚÁ·ÓÈο Ôͤ· Ô˘ Â›Ó·È ÂÓ‰ÂÈÎÙÈοÛÙÔȯ›· ÂÓ‰ÔÁÂÓÔ‡˜ ÌÂÈÔÓÂÎÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡(8). ∂ӉȷʤÚÔ˘Û· Â›Ó·È Ë ·Ó›¯Ó¢ÛË Ù˘ 3-ÌÂı˘ÏÔ-ÁÏÔ˘Ù·ÎÔÓÈ΋˜ Ô͢Ԣڛ·˜ Û 7 ·ÛıÂÓ›˜ (¶›Ó·Î·˜3), Û 6 ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ¤¯ÂÈ ÂȂ‚·Èˆı› Ì Ӥ˜·Ó·Ï‡ÛÂȘ. ∏ ·Ó·ÊÂÚfiÌÂÓË ·Ó¿ÚÎÂÈ· ‰ÂÓ ÂÓÙ¿Û-ÛÂÙ·È ÛÙËÓ Î·ÙËÁÔÚ›· ÙˆÓ ÔÚÈÛÙÈÎÒÓ ‰È·ÁÓÒÛˆÓ,

¶·È‰È·ÙÚÈ΋ 2003;66:118-127 Paediatriki 2003;66:118-127

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¶·È‰È·ÙÚÈ΋ 2003;66:118-127 Paediatriki 2003;66:118-127

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‰ÈfiÙÈ ¯Ú‹˙ÂÈ ÂÚ·ÈÙ¤Úˆ ÌÂÙÚ‹ÛÂˆÓ ÌÂÙ·‚ÔÏÈÎÒÓÔ˘ÛÈÒÓ Î·È ‚ÈÔ¯ËÌÈ΋˜ ‰ÈÂÚ‡ÓËÛ˘. ∏ ÓfiÛÔ˜ ·˘Ù‹‰È·ÎÚ›ÓÂÙ·È Û ٤ÛÛÂÚȘ ÎÏÈÓÈÎÔ‡˜ ˘ÔÙ‡Ô˘˜, ÂÎÙˆÓ ÔÔ›ˆÓ Ë ÂÓ˙˘ÌÈ΋ Ù·˘ÙÔÔ›ËÛË Â›Ó·È ÂÊÈÎÙ‹ÌfiÓÔÓ Û ¤Ó·Ó (6). ™˘ÓÂÎÙÈÌÒÓÙ·˜ fiÏ· Ù· ·ÓˆÙ¤ÚˆÛÙÔȯ›· Ì ·Ó·ÊÔÚ¤˜ Û ÌÂϤÙ˜ Î·È ·Ó·ÎÔÈÓÒÛÂȘ·fi ¿ÏϘ ¯ÒÚ˜ (OÏÏ·Ó‰›·, πÙ·Ï›·, °·ÏÏ›·)(2,9,26), ·ÏÏ¿ Î·È ·fi ¿ÏϘ ·Ó·ÊÔÚ¤˜ ‰È·ÁÓÒÛÂ-ˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ÛÙËÓ ∂ÏÏ¿-‰· (27), Û˘Ó¿ÁÂÙ·È fiÙÈ Ë ·Ó·ÊÂÚfiÌÂÓË ·ıÚÔÈÛÙÈÎ‹Û˘¯ÓfiÙËÙ· ÙˆÓ ‰È·ÁÓÒÛÂˆÓ ÙˆÓ ÂÏÂÁ¯fiÌÂÓˆÓ ÓÔ-ÛËÌ¿ÙˆÓ ˘ÔÏ›ÂÙ·È ÙÔ˘ Ú·ÁÌ·ÙÈÎÔ‡ ÌÂÁ¤ıÔ˘˜ÙÔ˘˜ ÛÙË ¯ÒÚ· Ì·˜. ∂Ô̤ӈ˜, Ë Â˘·ÈÛıËÙÔÔ›ËÛËÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ÙˆÓ ∫ª¡ Â›Ó·È ‚·ÛÈÎfi ˙ËÙÔ‡ÌÂÓÔÙ˘ ·È‰È·ÙÚÈ΋˜ ‰È·ÁÓˆÛÙÈ΋˜ ÛÙË ¯ÒÚ· Ì·˜. ¢ÈÂ-ıÓÒ˜, ÂÊ·ÚÌfi˙ÔÓÙ·È ÚÔÁÚ¿ÌÌ·Ù· ‰ÈÂÚ‡ÓËÛ˘Ì ÙÚÂȘ ηÙ¢ı‡ÓÛÂȘ (21,28):

- TË ‰È¿ÁÓˆÛË ÓÔÛÔ‡ÓÙˆÓ ·fi Èı·Ó‹ ÔÚÁ·ÓÈ΋ÔÍ˘Ô¿ıÂÈ·, Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÚÔÁÚ·ÌÌ¿ÙˆÓÂÌÂÚÈÛٷو̤Ó˘ ÎÏÈÓÈÎÔ-ÂÚÁ·ÛÙËÚȷ΋˜ ‰ÈÂÚ‡-ÓËÛ˘. ∂Ê·ÚÌfi˙ÔÓÙ·È Ô‰ËÁ›Â˜ ÎÏÈÓÈ΋˜ ·ÍÈÔÏfiÁË-Û˘ Î·È ÂÈÏÔÁ‹˜ ÙˆÓ Î·Ù¿ÏÏËÏˆÓ ‰È·ÁÓˆÛÙÈÎÒÓÂÍÂÙ¿ÛˆÓ.

- TËÓ ÂÊ·ÚÌÔÁ‹ Ì·˙ÈÎÒÓ ÚÔÁÚ·ÌÌ¿ÙˆÓ ÚÔÛ˘-Ìو̷ÙÈ΋˜ ‰È¿ÁÓˆÛ˘, ÛÙÔÓ ÓÂÔÁÓÈÎfi ÏËı˘ÛÌfi,20-25 ÂÓ˙˘ÌÈÎÒÓ ·Ó·ÚÎÂÈÒÓ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ·ÌÈÓÔ-ͤˆÓ, ÔÚÁ·ÓÈÎÒÓ Î·È ÏÈ·ÚÒÓ ÔͤˆÓ Ù˘ ‚-ÔÍ›‰ˆ-Û˘ ÙÔ˘ ÌÈÙÔ¯ÔÓ‰Ú›Ô˘. °È· ÙÔ ÏfiÁÔ ·˘Ùfi, ·ÍÈÔÔÈ›-Ù·È Ë Ì¤ıÔ‰Ô˜ ÙÔ˘ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÙˆÓ ·Î˘ÏÔηÚÓÈ-ÙÈÓÒÓ Û ‰Â›ÁÌ·Ù· ÛÙ·ÁfiÓˆÓ ·›Ì·ÙÔ˜ Ì ·Ó·Ï˘Ù‹Ê·ÛÌ·ÙÔÁÚ·Ê›·˜ Ì·˙ÒÓ (Tandem-MS). ∏ ÂͤٷÛËÂ›Ó·È Ù·¯Â›·, ÌÂÁ¿Ï˘ ¢·ÈÛıËÛ›·˜ Î·È ÂȉÈÎfiÙËÙ·˜.¶ÔÏÏ¿ ÚÔÁÚ¿ÌÌ·Ù· ·˘ÙÒÓ ÙˆÓ ‰ÔÎÈÌ·ÛÈÒÓ Û ‰È¿-ÊÔÚ˜ ¯ÒÚ˜ ·Ó·Ê¤ÚÔ˘Ó ‰È·ÁÓÒÛÂȘ ∫ª¡ Ì·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ· 1:2500 ÁÂÓÓ‹ÛÂȘ (21).

- TË ‰ÈÂÚ‡ÓËÛË ·È‰ÈÎÔ‡ ÏËı˘ÛÌÔ‡ Ô˘ ·Ó‹-ÎÂÈ ÛÙËÓ ÔÌ¿‰· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ‹ ÂÙÂÚÔ˙˘ÁˆÙÒÓÈı·ÓÔ‡ ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ (Û˘ÁÁÂÓ›˜ ·ÛıÂ-ÓÒÓ, ÚÔÁÂÓÓËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜, ‰ÈÂÚ‡ÓËÛË Û ı·Ófi-ÓÙ˜ SIDS).

∏ ‰È·ÊÔÚԉȷÁÓˆÛÙÈ΋ ÂÎÙ›ÌËÛË Èı·ÓÔ‡ ÓÔÛ‹-Ì·ÙÔ˜ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ÂÓÈÛ¯‡ÂÙ·È ·fi Ù· ¢-Ú‹Ì·Ù· ‚·ÛÈÎÒÓ ‚ÈÔ¯ËÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ÙˆÓ·ÛıÂÓÒÓ, Ô˘ ÂÍÂÙ¿˙ÔÓÙ·È Î·Ù¿ ÙËÓ ÚÔÛ‚ÔÏ‹ Ôͤ-ˆ˜ ÂÂÈÛÔ‰›Ô˘. ™ÙÔÓ ÌÂÁ·Ï‡ÙÂÚÔ ·ÚÈıÌfi ÙˆÓ ·ÛıÂ-ÓÒÓ Ù˘ ÌÂϤÙ˘ Ì·˜ ηı˘ÛÙÂÚ› ‹ Â›Ó·È ÂÈ̤ÚÔ˘˜Ë ÂͤٷÛË ÛÙÔ˘˜ ‰Â›ÎÙ˜ Ù˘ ÔÍÂÔ‚·ÛÈ΋˜ ÈÛÔÚÚÔ-›·˜ (pH ·›Ì·ÙÔ˜, ‰ÈÙÙ·ÓıÚ·ÎÈο, ¯¿ÛÌ· ·ÓÈfiÓÙˆÓ),Ù˘ ÁÏ˘Îfi˙˘, Ù˘ ·Ì̈ӛ·˜, Ù˘ ÎÂÙÔÓÔ˘Ú›·˜ ηÈÙˆÓ ·Ó·ÁˆÁÈÎÒÓ Ô˘ÛÈÒÓ ÛÙ· Ô‡Ú·. ∂ÈÚfiÛıÂÙ·,‰È·Ù·Ú·¯¤˜ ÛÙÔÓ ·ÛıÂÓ‹, fiˆ˜ Ë Ï¢ÎÔÂÓ›·, ËıÚÔÌ‚ÔÂÓ›·, Ë ·Ó·ÈÌ›·, Ë ·‡ÍËÛË ÙÔ˘ Ô˘ÚÈÎÔ‡ÔͤԘ, ÔÈ ‰È·Ù·Ú·¯¤˜ Ù˘ Ë·ÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ηÈ

Ù˘ ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘, ÙÔ˘ ÏÈȉ·ÈÌÈÎÔ‡ ÚÔ-Ê›Ï, Ë ·‡ÍËÛË Ù˘ ÎÚ·ÙÈÓÈ΋˜ ÎÈÓ¿Û˘, Ù˘ Ì˘-ÛÊ·ÈÚ›Ó˘ Î·È Ù˘ ∞-ÂÌ‚Ú˘˚΋˜ ÚˆÙ½Ó˘, Ú¤ÂÈÓ· ·ÍÈÔÏÔÁÔ‡ÓÙ·È Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ ˘Ô-„›·˜ ∫ª¡. ∂›Û˘, Ë ÔÛÌ‹ Î·È ÙÔ ¯ÚÒÌ· ÙˆÓ Ô‡-ÚˆÓ ·ÔÙÂÏÔ‡Ó Ô‰ËÁfi ÁÈ· ÌÂÙ·‚ÔÏÈÎfi ¤ÏÂÁ¯Ô ÔÚ-Á·ÓÈ΋˜ Ô͢Ԣڛ·˜ (29). ∂Ó‰ÂÈÎÙÈ΋ ·Í›· ¤¯Ô˘Ó ηȉÔÎÈ̷ۛ˜ ·‰Ú‹˜ ·Ó›¯Ó¢Û˘ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÌÂÎÔÈÓ‹ ¯ËÌÈ΋ Û˘ÌÂÚÈÊÔÚ¿. ∏ ‰ÔÎÈÌ·Û›· ·Ó›¯Ó¢-Û˘ ıÂÈÒ‰Ô˘˜ (sulphite test) ÂÊ·ÚÌfi˙ÂÙ·È Û ÊÚ¤-Ûη Ô‡Ú· ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ‰È·ÁÓˆÛÙÈÎÒÓ Ô˘ÛÈÒÓ Û·Ó¿ÚÎÂÈ· ÙˆÓ ÂÓ˙‡ÌˆÓ “ÔÍÂȉ¿Û˘ ÙÔ˘ ıÂÈÒ‰Ô˘˜Î·È Û˘Ì·Ú¿ÁÔÓÙ· ÙÔ˘ ÌÔÏ˘‚‰ÂÓ›Ô˘”. ∏ ‰ÔÎÈÌ·Û›·Ù˘ ‰ÈÓÈÙÚÔÊ·ÈÓ˘Ï˘‰Ú·˙›Ó˘ (DPNH) ‰›ÓÂÈ ıÂÙÈ΋·ÓÙ›‰Ú·ÛË Û ·˘ÍË̤Ó˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ÙˆÓ ‚-ÎÂ-ÙÔ-ÔͤˆÓ (MSUD) Î·È ÙÔ˘ ÓÈÙÚÔÚÔ˘Ûȉ›Ô˘ (brandreaction) Û ·‡ÍËÛË ÙˆÓ ıÂÈÔ‡¯ˆÓ ÔͤˆÓ (΢ÛÙ›-Ó˘, ÔÌÔ΢ÛÙ›Ó˘, ÁÏÔ˘Ù·ıÂÈfiÓ˘ Î·È Ê·Ú̿ΈÓ).∏ Ó¢ÚÔ·ÂÈÎÔÓÈÛÙÈ΋ ‰ÈÂÚ‡ÓËÛË Û˘Ì‚¿ÏÏÂÈ ÛÙˉÈ¢ÎÚ›ÓËÛË Ù˘ Ó¢ÚÔÏÔÁÈ΋˜ ‚Ï¿‚˘ ηÈ, Û ÔÚÈ-Ṳ̂Ó˜ ÂÚÈÙÒÛÂȘ, ÛÙË ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘ (ÌËÎÂÙˆÙÈ΋ ˘ÂÚÁÏ˘ÎÈÓ·ÈÌ›·, L-2-˘‰ÚÔ͢-ÁÏÔ˘Ù·ÚÈ΋Ô͢Ԣڛ·, ÁÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ· Ù‡Ô˘ π, Û‡Ó‰ÚÔÌÔLeigh) (30).

™Â ·ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈο ÎÏÈÓÈÎÔ-ÂÚÁ·ÛÙËÚÈ·-ο Â˘Ú‹Ì·Ù· Èı·Ó‹˜ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜, ·ÏÏ¿·ÚÓËÙÈο ‹ ·Û·Ê‹ ·ÔÙÂϤÛÌ·Ù· ÙÔ˘ Ê¿ÛÌ·ÙÔ˜·Ó¿Ï˘Û˘ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓ, Ú¤-ÂÈ Ó· ‰ÈÂÚ¢ÓÒÓÙ·È ÌÂÙ·‚ÔÏÈο ÚÔ˚fiÓÙ· Ì ÂȉÈ-ÎfiÙÂÚÔ ÙÚfiÔ ÌÂıÔ‰ÔÏÔÁ›·˜ (8). ™¯ÂÙÈο, ÂÊ·ÚÌfi-˙ÂÙ·È Ë ÔÛÔÙÈ΋ ̤ÙÚËÛË ÛÙ· ˘ÁÚ¿ ÙÔ˘ ÛÒÌ·ÙÔ˜(·›Ì·, Ô‡Ú·, ·ÌÓÈ·Îfi Î·È ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi)ÂȉÈÎÒÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, Ì ÙȘ ÌÂıfi‰Ô˘˜ GC-MSÎ·È Tandem-MS. ¢È·ÁÓˆÛÙÈÎÔ› Â›Ó·È ÔÈ ÚÔÛ‰ÈÔÚÈ-ÛÌÔ› ÙÔ˘ ÁÏÔ˘Ù·ÚÈÎÔ‡ Î·È 3-˘‰ÚÔ͢-ÁÏÔ˘Ù·ÚÈÎÔ‡ÔͤԘ › ˘Ô„›·˜ ÁÏÔ˘Ù·ÚÈ΋˜ Ô͢Ԣڛ·˜ Ù‡Ô˘(π), ÙÔ˘ ÌÂı˘ÏÔÌ·ÏÔÓÈÎÔ‡ ÔͤԘ ÛÙÔÓ ÂÏÏÂÈÌÌ·ÙÈÎfiÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÎÔ‚·Ï·Ì›Ó˘, ÙÔ˘ ¡-·ÎÂÙ˘ÏÔ·-Û·ÚÙÈÎÔ‡ ÔͤԘ ÛÙË ÓfiÛÔ Canavan, Ù˘ ËÏÂÎÙÚÈ-ÎÔ·ÎÂÙfiÓ˘ (succinylace-tone) ÛÙËÓ Ù˘ÚÔÛ˘Ó·ÈÌ›·Ù‡Ô˘ (π), ÙÔ˘ 4-˘‰ÚÔ͢-‚Ô˘Ù˘ÚÈ· ÔͤԘ, ÙÔ˘ ÌÂ-‚·ÏÔÓÈÎÔ‡ ÔͤԘ, ÙˆÓ L- Î·È D-ÈÛÔÌÂÚÒÓ ÙÔ˘ 2-˘‰ÚÔ͢-ÁÏÔ˘Ù·ÚÈÎÔ‡ ÔͤԘ ÛÙȘ ·ÓÙ›ÛÙÔȯ˜ Ô͢-Ô˘Ú›Â˜. ∂›Û˘, ÔÛÔÙÈο ÚÔÛ‰ÈÔÚ›˙ÂÙ·È ÙÔ ÔÚÔÙÈ-Îfi Ô͇ ÛÙȘ ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈ-ÛÌÔ‡ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜, › ˘Ô„›·˜ ÌÂÚÈ΋˜ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜. ∏ ‰ÈÂÚ‡ÓËÛË Ù˘ ·‡ÍË-Û˘ ÂȉÈÎÒÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, › ˘Ô„›·˜ ÌÂÈÔÓÂ-ÎÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÂȉÈÎÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ ·ÓÙÈ-‰Ú¿ÛˆÓ, ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÂȉÈÎÒÓÙ¯ÓÈÎÒÓ ·Ó¿Ï˘Û˘ GC-MS, fiˆ˜ ÛÙȘ ÓfiÛÔ˘˜:Û‡Ó‰ÚÔÌÔ Smith-Lemli-Opitz (·‡ÍËÛË 7b-cholesta-nol), ÙÚÈÌÂı˘Ï·ÌÈÓÔ˘Ú›· (trymethylaminuria) ÛÂ

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·125

·Ó¿ÚÎÂÈ· Ù˘ Ë·ÙÈ΋˜ Û˘ÓıÂÙ¿Û˘ (trimethy-amine N-oxide), ‰ÈÌÂı˘ÏÔÁÏ˘ÎÈÓÔ˘Ú›· (dimethylgly-cinuria) Û ·Ó¿ÚÎÂÈ· Ù˘ ·Ê˘‰ÚÔÁÔÓ¿Û˘(dimethylglycine dehydrogenase), ÌÂÈÔÓÂÎÙÈÎfi˜ ÌÂ-Ù·‚ÔÏÈÛÌfi˜ ÙˆÓ ¯ÔÏÈÎÒÓ ÔͤˆÓ Ì ·‡ÍËÛË ÂӉȿÌÂ-ÛˆÓ ÚÔ˚fiÓÙˆÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘˜, ÂÓ˙˘ÌÈ΋·Ó¿ÚÎÂÈ· ÛÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÎÚ·ٛÓ˘ Ì·‡ÍËÛË ÛÙ· Ô‡Ú· ÙÔ˘ ÁÔ˘·ÓȉÈÓÔÍÂÈÎÔ‡ ÔͤԘ(guanidino-acetate: GAMT deficiency). ∏ ·Ó¿Ú-ÎÂÈ· ÙˆÓ ÂÓ˙‡ÌˆÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ Ó¢Úԉȷ-‚È‚·ÛÙÒÓ ÂϤÁ¯ÂÙ·È Ì ÙÔÓ ÔÛÔÙÈÎfi ÚÔÛ‰ÈÔÚÈÛÌfiÙÔ˘˜ ÛÙÔ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi Ô˘ÛÈÒÓ, fiˆ˜ ›-Ó·È ÙÔ Á-·ÌÈÓÔ‚Ô˘Ù˘ÚÈÎfi Ô͇ (GABA), ÙÔ ÔÌÔ‚·Ï˘-ÓÈÎfi Ô͇ (HVA), Ë ÓÙÔ·Ì›ÓË, ÙÔ 5-˘‰ÚÔ͢-ÈÓ‰ÔÏÔ-ÔÍÈÎfi Ô͇ Î·È ÔÈ ÙÂÚ›Ó˜. ™¯ÂÙÈο, ··ÈÙÔ‡ÓÙ·È ÂÈ-‰ÈΤ˜ Û˘Óı‹Î˜ Ï‹„ˆ˜ Î·È ·Ó¿Ï˘Û˘ ÙˆÓ ·ÓÙ›-ÛÙÔȯˆÓ Ô˘ÛÈÒÓ (11).

∏ ÂÓ‰ÔÁÂÓ‹˜ ·Ù¤ÏÂÈ· Ù˘ Û˘ÓÂÚÁÈ΋˜ Ì ¤Ó˙˘Ì·‰Ú¿Û˘ ÙˆÓ ‚ÈÙ·ÌÈÓÒÓ, fiˆ˜ Ù˘ ÎÔ‚·Ï·Ì›Ó˘, Ù˘‚ÈÔÙÈÓȉ¿Û˘ Î·È Ù˘ ˘ÚȉÔ͛Ӣ, ÂϤÁ¯ÂÙ·È Ì ÂÈ-‰È΋ ÁÈ· οı ÂÚ›ÙˆÛË Ì¤ıÔ‰Ô (13). O ÂÓ‰ÔÁÂÓ‹˜ÌÂÈÔÓÂÎÙÈÎfi˜ ÌÂÙ·‚ÔÏÈÛÌfi˜ Ù˘ ÎÔ‚·Ï·Ì›Ó˘ ÂϤÁ-¯ÂÙ·È ÂÌ̤ۈ˜ Ì ÙËÓ ·Ó›¯Ó¢ÛË Ù˘ ÌÂı˘ÏÔÌ·ÏÔ-ÓÈ΋˜ Ô͢Ԣڛ·˜ Î·È ÔÌÔ΢ÛÙ˘ÓÔ˘Ú›·˜ (¶›Ó·Î·˜ 2,·ÛıÂÓ‹˜ 5‚). ∏ ·Ó¿ÚÎÂÈ· Û˘ÌÌÂÙÔ¯‹˜ Ù˘ ˘ÚÈ-‰Ô͛Ӣ ÛÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi ÙÔ˘ GABA ÛÙȘ ÂÁÎÂÊ·-ÏÈΤ˜ ÏÂÈÙÔ˘ÚÁ›Â˜ ‰È·ÈÛÙÒÓÂÙ·È ÂÌ̤ۈ˜, Ì ÙËÓ¿ÌÂÛË ˘Ô¯ÒÚËÛË ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Û·ÛÌÒÓ ÌÂÙ¿ÙË ¯ÔÚ‹ÁËÛ‹ Ù˘. ∏ ·Ó·Ú΋˜ ÂÓ˙˘ÌÈ΋ ‰Ú¿ÛËÙ˘ ‚ÈÔÙÈÓȉ¿Û˘ ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Û¯ÂÙÈο ‡ÎÔÏ·Û ‰Â›ÁÌ· ·›Ì·ÙÔ˜ ÙÔ˘ ·ÛıÂÓÔ‡˜. ∂Ó‰ÂÈÎÙÈο, ÂϤÁ-¯ÔÓÙ·È ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ ÙÔ˘ Á·Ï·ÎÙÈÎÔ‡ ÔͤԘ ÛÙÔ·›Ì· Î·È ÛÙÔ ∂¡À, Î·È ÛÙ· Ô‡Ú· ÙÔ Ê¿ÛÌ· ÙˆÓ ÔÚ-Á·ÓÈÎÒÓ ÔͤˆÓ, Ù· ÔÔ›· Û˘Ó‹ıˆ˜ Â›Ó·È ·ıÔÏÔÁÈ-ο ÙËÓ ÂÚ›Ô‰Ô ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Ù˘ ÓfiÛÔ˘. ¶·Ú’ fiÙÈË Û˘¯ÓfiÙËÙ· Ù˘ ·Ó¿ÚÎÂÈ·˜ ·˘Ù‹˜ ÛÙËÓ ∂˘ÚÒˉÂÓ Â›Ó·È Ôχ Û¿ÓÈ· (1:60-100 ¯ÈÏÈ¿‰Â˜ ÁÂÓÓ‹-ÛÂȘ), ·fi ÙȘ ·ÓˆÙ¤Úˆ ·Ó·Ï‡ÛÂȘ ‰ÂÓ ‰È·ÈÛÙÒıË-ΠÂÓ‰ÂÈÎÙÈ΋ Ô͢Ԣڛ·. ∞ӷχÛÂȘ ÔÚÁ·ÓÈÎÒÓ Ôͤ-ˆÓ ·fi 42 ·ÛıÂÓ›˜ (¶›Ó·Î·˜ 3, ¡Ô 12) ·ÚÔ˘Û›·-Û·Ó ·‡ÍËÛË Û ÔÚÈṲ̂ӷ ÂÍ ·˘ÙÒÓ, Ô˘ ‰ÂÓ ÙÂÎÌË-ÚÈÒÓÔ˘Ó ÂȉÈ΋ ÂÈÎfiÓ· ÂÓ‰ÔÁÂÓÔ‡˜ ÂÓ˙˘ÌÈ΋˜ ·ÓÂ-¿ÚÎÂÈ·˜. ™˘¯Ó¿, ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔۋ̷ٷ›Ù ÌÂÌÔӈ̤Ó˜ ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜, fiˆ˜ ÙÔ˘‹·ÙÔ˜, ÙˆÓ ÓÂÊÚÒÓ, ÙÔ˘ ÂÓÙ¤ÚÔ˘ ‹ Ë Ï‹„Ë Ê·Ú-Ì¿ÎˆÓ Î·È ÂȉÈ΋˜ ‰È·ÙÚÔÊ‹˜, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‰È·Ù·-Ú·¯¤˜ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, Ë ·ÍÈÔÏfiÁËÛË ÙˆÓÔÔ›ˆÓ Â›Ó·È ·ÌÊ›‚ÔÏË (8,12).

¶ÔÏÏ¿ ·Ú·ÂÌÙÈο Ô˘ Û˘ÓÔ‰Â‡Ô˘Ó Ù· ‰Â›Á-Ì·Ù· ·ÛıÂÓÒÓ, ·Ó·Ê¤ÚÔ˘Ó ÙËÓ ÎÏÈÓÈ΋ ÙÔ˘˜ ηٿ-ÛÙ·ÛË Ì ÁÂÓÈÎÔ‡˜ fiÚÔ˘˜, fiˆ˜ ·Ó·Ù˘Íȷ΋ ηȄ˘¯ÔÎÈÓËÙÈ΋ ηı˘ÛÙ¤ÚËÛË, ·Ó·Ù˘ÍȷΤ˜ ·ÓˆÌ·-ϛ˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘, ÂÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË Î·È Ô-

Ï˘ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜, ÂÈÏË„›·, ‚ÚÂÊÈ΋ ˘ÔÙÔÓ›·,ÏÔÈÌÒÍÂȘ (18). ∞˘Ù¤˜ ÔÈ ÁÂÓÈΤ˜ ·Ó·ÊÔÚ¤˜ ‰È·Ù·-Ú·¯ÒÓ, ·Ó Î·È ‰ÂÓ ·ÔÙÂÏÔ‡Ó Î‡ÚÈ· ÎÏÈÓÈ΋ ÂΉ‹-ψÛË ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜, ÔÚÈṲ̂Ó˜ ÊÔÚ¤˜ÔÊ›ÏÔÓÙ·È Û ∫ª¡. ∏ ÂÚ·ÈÙ¤Úˆ ηÙ‡ı˘ÓÛË Ù˘‰ÈÂÚ‡ÓËÛ˘ ηıÔÚ›˙ÂÙ·È Ì ÙËÓ ·Ó·ÊÔÚ¿ ÂÚÈÛÛfi-ÙÂÚˆÓ ÛÙÔȯ›ˆÓ ÙˆÓ ·ÛıÂÓÒÓ.

™˘ÌÂÚ·ÛÌ·ÙÈο, Ù· ·ÓˆÙ¤Úˆ ·Ó·‰ÂÈÎÓ‡Ô˘Ó ÂÓ̤ÚÂÈ ÙÔ Ì¤ÁÂıÔ˜ Î·È Ù· ‰È·ÁÓˆÛÙÈο ÚÔ‚Ï‹Ì·Ù·ÙˆÓ ÂÏÂÁ¯fiÌÂÓˆÓ ÓÔÛËÌ¿ÙˆÓ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘-ÛÌfi. ∏ ·ÎÚÈ‚‹˜ ·ÔÙ‡ˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ·˘ÙÒÓÙˆÓ ÓÔÛËÌ¿ÙˆÓ, fiˆ˜ Î·È Ë ÏËÚ¤ÛÙÂÚË ÂÍ·ÁˆÁ‹Û˘ÌÂÚ·ÛÌ¿ÙˆÓ ·fi ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ È·ÙÚÈ΋˜·Ú¤Ì‚·Û˘ ÛÙÔ˘˜ ÂÏÂÁ¯fiÌÂÓÔ˘˜ ·ÛıÂÓ›˜, ÌÔ-ÚÔ‡Ó Ó· ÂÈÙ¢¯ıÔ‡Ó Ì ÙËÓ ÂÚ·ÈÙ¤Úˆ ·Ó¿Ù˘ÍËÙˆÓ ÂÍÂȉÈÎÂ˘Ì¤ÓˆÓ È·ÙÚÈÎÒÓ ÌÔÓ¿‰ˆÓ ‰È¿ÁÓˆÛ˘,·ÁˆÁ‹˜ Î·È ¤Ú¢ӷ˜ ÛÙË ¯ÒÚ· Ì·˜.

∂˘¯·ÚÈÛٛ˜ ∂˘¯·ÚÈÛÙԇ̠ÂηÙÔÓÙ¿‰Â˜ È·ÙÚÔ‡˜ ·fi fiÏ· Ù· ÓÔÛÔÎÔ-

Ì›· Ù˘ ¯ÒÚ·˜, ÔÈ ÔÔ›ÔÈ ÛÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô 1996-2001Ì¿˜ ·¤ÛÙÂÈÏ·Ó ‰Â›ÁÌ·Ù· ÙˆÓ ·ÛıÂÓÒÓ Ì·˙› Ì ÂÓËÌÂÚˆÙÈοÛËÌÂÈÒÌ·Ù·. ∂›Û˘, ¢¯·ÚÈÛÙԇ̠ÙËÓ Î·. ∂. ªÈ¯ÂϷοÎË,ηıÒ˜ Î·È ÙÔ ˘fiÏÔÈÔ ÂÈÛÙËÌÔÓÈÎfi ÚÔÛˆÈÎfi ÙÔ˘ πÓÛÙÈ-ÙÔ‡ÙÔ˘ ÀÁ›·˜ ÙÔ˘ ¶·È‰ÈÔ‡ Ù˘ ∞ı‹Ó·˜ ÁÈ· ÙË Û˘Ì‚ÔÏ‹ ÙÔ˘˜ÛÙËÓ ÔÏÔÎÏ‹ÚˆÛË ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÂÍÂÙ¿ÛˆÓ.

µÈ‚ÏÈÔÁÚ·Ê›·1. Scriver CR. Garrrod’s foresight: our hindsight. J Inherit

Metab Dis 2001;24:93-116. 2. Underwood JC. Genetic and environmental causes of

diseases. In: General and systemic Pathology. 2nd ed. ¡ewYork: Churchill Livingstone; 1996. p. 31-60.

3. Dionisi-Vici C, Rizzo C, Burlina AB, Caruso U, Sabetta G,Uziel G et al. Inborn errors of metabolism in the Italianpediatric population: a national retrospective survey. JPediatr 2002;140:321-327.

4. Green A, Pollitt RJ. Population newborn screening forinherited metabolic disease: current UK perspectives. JInherit Metab Dis 1999;22:572-579.

5. Applegarth DA, Toone JR, Lowry RB. Incidence of inbornerrors of metabolism in British Columbia, 1969-1996.Pediatrics 2000;105:e10.

6. Scriver CR, Beaudet AL, Sly WS, Valle. The metabolic andmolecular bases of inherited disease. In: Genetics,biochemistry and molecular bases of variant humanphenotypes. 8th ed. ¡ew York: McGraw-Hill; V1,1,3-45.V1,66, p. 1327-1396. V2,93; 2001. p. 2125-2140.

7. Tom Strachan, Read AP. Molecular pathology. Humanmolecular genetics. 2nd ed. U.K.: Bios; 1999. p. 377-422.

8. Hoffman GF, Nyhan WL, Zschoche J, Kahler SG, MayatepekE. Organic acid analysis: approach to the diagnosis oforganic acidurias. In: Inherited metabolic diseases. Baltimore:Lippincott Williams & Wilkins; 2002. p. 319-328.

9. Lehnert W. Long-term results of selective screening for inbornerrors of metabolism. Eur J Pediatr 1994;153(7 Suppl 1):S9-13.

¶·È‰È·ÙÚÈ΋ 2003;66:118-127 Paediatriki 2003;66:118-127

126

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·126

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127

10. ª·ÙÛ·ÓÈÒÙ˘ ¡, ∫·Ú¿ıÈÔ˜ £ Î·È Û˘Ó. ™‡ÌÊ˘Ù˜ ‰È·Ù·Ú·-¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡. ™ÙÔ: ª·ÙÛ·ÓÈÒÙ˘. ¶·È‰È·ÙÚÈ΋,∆fiÌÔ˜ ππ. 1Ë ÂΉ. ∞ı‹Ó·: ∂ΉfiÛÂȘ §›ÙÛ·˜; 1999. ÛÂÏ. 896-1130.

11. Sweetman L. Organic acid analysis. Techniques indiagnostic human biochemical genetics. A laboratorymanual. New York: Wiley-Liss; 1991. p. 143-176.

12. Kumps A, Duez P, Mardens Y. Metabolic, nutritional,iatrogenic, and artifactual sources of urinary organic acids:a comprehensive table. Clin Chem 2002;48:708-717.

13. Hommes GF. Techniques in diagnostic human biochemicallaboratories: a laboratory manual. 1st ed. New York: Wiley-Liss; 1991. p. 5-120.

14. Vreken P, van Lint AE, Bootsma AH, Overmars H, WandersRJ, van Gennip AH. Rapid diagnosis of organic acidemiasand fatty-acid oxidation defects by quantitative electrospraytandem-MS acyl-carnitine analysis in plasma. Adv Exp MedBiol 1999;466:327-337.

15. Tanaka K, Hine DG. Compilation of gas chromatographicretention indices of 163 metabolically important organicacids, and their use in detection of patients with organicacidurias. J Chromatogr 1982;239:301-322.

16. Rashed MS, Bucknall MP, Little D, Awad A, Jacob M,Alamoudi M et al. Screening blood spots for inborn errors ofmetabolism by electrospray tandem mass spectrometrywith a microplate batch process and a computer algorithmfor automated flagging of abnormal results. Clin Chem1997;43:2106-2113.

17. Hoffmann GF. Selective screening for inborn errors ofmetabolism - past, present and future. Eur J Pediatr1994;153 (Suppl 1):S2-8.

18. Lyon G, Adams RD, Konodny EH. Neurology of hereditarymetabolic diseases of children. Laboratory tests for thediagnosis of hereditary metabolic encephalopathies. 2nded. New York: McGraw-Hill; 1996. p. 340-350, 6-41.

19. Gibson KM, Hoffmann GF, Hodson AK, Bottiglieri T, JakobsC. 4-Hyrdoxybutyric acid and the clinical phenotype ofsuccinic semialdehyde dehydrogenase deficiency, aninborn error of GABA metabolism. Neuropediatrics1998;29:14-22.

20. Wanders RJ, Vreken P, den Boer ME, Wijburg FA, vanGennip AH, Ijlst L. Disorders of mitochondrial fatty acyl-CoAB-oxidation. J Inherit Metab Dis 1999;22:442-487.

21. Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, ShihVE, Johnson DM et al. Tandem mass spectrometric analysisfor amino, organic, and fatty acid disorders in newborndried blood spots: a two-year summary from the NewEngland Newborn Screening Program. Clin Chem2001;47:1945-1955.

22. Vockley J. The changing face of disorders of fatty acidoxidation. Mayo Clin Proc 1994;69:249-257.

23. Stern HJ. Lactic acidosis in paediatrics: clinical andlaboratory evaluation. Ann Clin Biochem 1994;31:410-419.

24. Fernandes J, Saudubray JM, Huber J. Diagnosticprocedures: function tests and postmortem protocol. In:Fernandes J, Saudubray JM, Van den Berghe G, editors.Inborn metabolic diseases. 3rd ed. Heidelberg: Springer;2000. p. 43-51.

25. Brusilow SW, Maestri NE. Urea cycle disorders: diagnosis,pathophysiology, and therapy. Adv Pediatr 1996;43:127-170.

26. Nuoffer JM, Baumgartner M, Detournay B, DeLonlay P,Nassogne MC, Touati G et al. Diagnosis of inborn errors ofmetabolism in France - a national prospective study. JInherit Metab Dis 1999;22 (Suppl 1):125.

27. Evangeliou A, Lionis C, Michailidou H, Spilioti M, KanitsakisA, Nikitakis P et al. Selective screening for inborn errors ofmetabolism: the primary care-based model in rural Crete. JInherit Metab Dis 2001;24:877-880.

28. ¶ÂÙÚ›‰Ô˘ E, ∫·Ú¿ıÈÔ˜ £, ∆ÚȯfiÔ˘ÏÔ˜ ¢ ÂÈÛÙËÌÔÓÈÎÔ›Û˘ÓÙÔÓÈÛÙ¤˜. ¶ÚÔÛ˘Ìو̷ÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ·È‰ÈÒÓ Î·È ÂÊ‹-‚ˆÓ. ∂Ó‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡. ∞ı‹Ó·:∑‹Ù·; 1999. ÛÂÏ. 88-90.

29. Nyhan WL, Ozand PT. Disorders of organic acids. In: Atlasof metabolic diseases. 1st ed. London: Chapman & Hall;1998. p. 1-291.

30. Brismar J, Ozand PT. CT and MR of the brain in thediagnosis of organic acidemias. Experiences from 107patients. Brain Dev 1994;16 (Suppl):104-124.

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Evaluation of compliance with chelation therapy in children with beta-thalassaemia major K. Papadopoulou - Legbelou1, M. Athanasiou - Metaxa2, G. Varlamis3, S. Karamperis3

∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞ ORIGINAL ARTICLE

�¶ÂÚ›ÏË„Ë: ∆Ô Ù·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛË˜Î·È ·ÔÛȉ‹ÚˆÛ˘ ¤¯ÂÈ ·˘Í‹ÛÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ·Û¯fiÓÙˆÓ ·fi ‚-ª∞, ΢ڛˆ˜ fiÙ·Ó ˘¿Ú¯ÂÈ Î·Ï‹Û˘ÌÌfiÚʈÛË ÛÙË ıÂڷ›·. ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘‹Ù·Ó Ó· ‰ÈÂÚ¢ÓËı› Ë Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹-ÚˆÛË Û ¿Û¯ÔÓÙ˜ ·fi ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÂÙ·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘-·ÔÛȉ‹ÚˆÛ˘·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ Î·È Ë Û˘Û¯¤ÙÈÛ‹ Ù˘ ̉ȿÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ Ë ËÏÈΛ·, ÙÔ Ê‡ÏÔ, ˯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘, ÙÔ Û‡ÓÔÏÔÙˆÓ ÌÂÙ·ÁÁ›ÛˆÓ, Ë ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ÙËÌÂÙ¿ÁÁÈÛË Î·È Ë ÊÂÚÚÈÙ›ÓË ÙÔ˘ ÔÚÔ‡. ªÂÏÂÙ‹ıËηÓ90 ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ (48 ·ÁfiÚÈ· Î·È 42ÎÔÚ›ÙÛÈ·) ËÏÈΛ·˜ 3-18 ¯ÚfiÓˆÓ (̤ÛË ËÏÈΛ·:12,3±4,4 ¤ÙË), ÔÈ ÔÔ›ÔÈ ‚Ú›ÛÎÔÓÙ·Ó Û ٷÎÙÈÎfiÚfiÁÚ·ÌÌ· ÌÂÙ·ÁÁ›ÛÂˆÓ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘Î·È ¿Ú¯È˙·Ó ·ÔÛȉ‹ÚˆÛË Û ÙÈÌ‹ ÊÂÚÚÈÙ›Ó˘ ÂÚ›-Ô˘ 1000 ng/ml. OÈ ¿Û¯ÔÓÙ˜ ¯ˆÚ›ÛÙËÎ·Ó Û 3ÔÌ¿‰Â˜ ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· (ÔÌ¿‰· ∞: <10ÂÙÒÓ, ÔÌ¿‰· µ: 10-15 ÂÙÒÓ, ÔÌ¿‰· °: >15 ÂÙÒÓ) ηÈÛ 3 ÔÌ¿‰Â˜ ·Ó¿ÏÔÁ· Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ·ÔÛȉ‹ÚˆÛË (1Ë ÔÌ¿‰·: η΋, 2Ë ÔÌ¿‰·: ̤ÙÚÈ·,3Ë ÔÌ¿‰·: ηϋ). ¢È·ÈÛÙÒıËΠη΋ Û˘ÌÌfiÚʈÛËÛ 11 ·ÛıÂÓ›˜ (12%), ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË Û 20(22%) Î·È Î·Ï‹ Û˘ÌÌfiÚʈÛË Û 59 ·ÛıÂÓ›˜(66%). ∏ ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË ·Ú·ÙËÚ‹ıËÎÂÌ ÙËÓ ·‡ÍËÛË Ù˘ ËÏÈΛ·˜, ÙˆÓ ¯ÚfiÓˆÓ ·ÔÛȉ‹-ÚˆÛ˘ Î·È ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÌÂÙ·ÁÁ›ÛˆÓ, ÂÓÒ ·fiÙÔ Ê‡ÏÔ Ê¿ÓËΠfiÙÈ Ù· ·ÁfiÚÈ· ›¯·Ó ¯ÂÈÚfiÙÂÚËÛ˘ÌÌfiÚʈÛË Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ·. ∂›Û˘, Ëη΋ Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË Ê¿ÓËΠfiÙÈÛ¯ÂÙ›˙ÂÙ·È Ì ˘„ËϤ˜ ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘ ÙÔ˘ ÔÚÔ‡.

�Abstract: Regular transfusion and chelationtherapy in ‚-thalassaemia have improved survival,particularly when associated with optimalcompliance. The aim of this study was to investigatecompliance with chelation therapy of patients with‚-thalassaemia major who were treated with regulartransfusions and chelation therapy, and therelationships between compliance and age, sex,duration of chelation therapy, number of bloodtransfusions and post-transfusional haemoglobinand serum ferritin levels. Ninety patients, 48 boysand 42 girls, aged 3-18 years (mean age: 12.3±4.4years) were studied. They were all receiving regulartransfusions and started chelation therapy withdesferrioxamine at serum ferritin levels ofapproximately 1000 ng/ml. The patients weredivided into three groups according to age (groupA: <10 years, group B: 10-15 years, group C: >15years). They were also classified into three groupsaccording to compliance with chelation therapy(group I: poor, group II: moderate, group III: optimalcompliance). Eleven patients (12%) exhibited poorcompliance, 20 (22%) moderate and 59 (66%)optimal compliance. The poorest compliance withchelation therapy was observed in older patientswith a higher number of blood transfusions andboys showed worse compliance than girls. Thenon-compliant patients had a higher mean serumferritin level. In this study the majority of patientsshowed good compliance with chelation therapy.The age at commencement of desferrioxaminetreatment appears to be an important determinant

1 °ÂÓÈÎfi ¶ÂÚÈÊÂÚÂÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô “¶··ÁˆÚÁ›Ô˘”, £ÂÛÛ·ÏÔÓ›ÎË

2 A’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ∞ÚÈÛÙÔÙ¤ÏÂÈÔ˘ ¶·ÓÂÈÛÙ‹ÌÈÔ˘£ÂÛÛ·ÏÔӛ΢

3 ¢’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ∞ÚÈÛÙÔÙ¤ÏÂÈÔ˘ ¶·ÓÂÈÛÙ‹ÌÈÔ˘£ÂÛÛ·ÏÔӛ΢

1 “Papageorgiou” General Hospital, Thessaloniki

2 1st Paediatric Clinic of Aristotelion University, Thessaloniki

3 4th Paediatric Clinic of Aristotelion University, Thessaloniki

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∂ÈÛ·ÁˆÁ‹∆ËÓ ÙÂÏÂ˘Ù·›· ÂÈÎÔÛ·ÂÙ›·, Ë ıÂڷ›· Ù˘ ÔÌfi-

˙˘Á˘ ‚-ÌÂÛÔÁÂȷ΋˜ ·Ó·ÈÌ›·˜ (‚-ª∞) ÂÚÈÏ·Ì‚¿-ÓÂÈ Ù·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ·ÁÁ›ÛÂˆÓ Î·È ˘Ô‰fiÚÈ·¯ÔÚ‹ÁËÛË Ù˘ ‰ÂÛÊÂÚÈÔÍ·Ì›Ó˘ (DFO) ÁÈ· ÙËÓ ·ÓÙÈ-ÌÂÙÒÈÛË Ù˘ ·ÈÌÔÛȉ‹ÚˆÛ˘ (1). ∆Ô Ù·ÎÙÈÎfi Úfi-ÁÚ·ÌÌ· ÌÂÙ·ÁÁ›ÛÂˆÓ ¤¯ÂÈ ÌÂÈÒÛÂÈ ÙȘ ÂÈÏÔΤ˜Ù˘ ÌË ·ÔÙÂÏÂÛÌ·ÙÈ΋˜ ÂÚ˘ıÚÔÔ›ËÛ˘ Î·È Ù˘·Ó·ÈÌ›·˜, ÂÓÒ Ë ÂÊ·ÚÌÔÁ‹ Ù˘ Û˘ÛÙËÌ·ÙÈ΋˜ ·Ô-Ûȉ‹ÚˆÛ˘ ¤¯ÂÈ ·˘Í‹ÛÂÈ ÛËÌ·ÓÙÈο ÙÔÓ Ì¤ÛÔ fiÚÔÂÈ‚›ˆÛ˘ ÙˆÓ ·Û¯fiÓÙˆÓ. ¶·Ú’ fiÏ· ·˘Ù¿, ÔÈ ÂÈ-ÏÔΤ˜ ·fi Ù· ‰È¿ÊÔÚ· fiÚÁ·Ó·, Ô˘ ÔÊ›ÏÔÓÙ·ÈÛÙËÓ ·ÈÌÔÛȉ‹ÚˆÛË, ‰ÂÓ ¤¯Ô˘Ó ÂÍ·ÏÂÈÊı›, ΢ڛˆ˜ÏfiÁˆ Ù˘ η΋˜ Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ·ÔÛȉ‹ÚˆÛË‹ Ù˘ ÌË ¤ÁηÈÚ˘ ¤Ó·ÚÍ‹˜ Ù˘ (2). ∆· ·ÚÈ· fiÚÁ·-Ó· Ô˘ ÚÔÛ‚¿ÏÏÔÓÙ·È ·fi ÙËÓ ÂÓ·fiıÂÛË Ûȉ‹-ÚÔ˘ Â›Ó·È Ë Î·Ú‰È¿, ÙÔ ‹·Ú Î·È ÔÈ ÂÓ‰ÔÎÚÈÓ›˜ ·‰¤-Ó˜ (3).

™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ó· ‰ÈÂÚ¢ÓËı› Ë Û˘Ì-ÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË Û ¿Û¯ÔÓÙ˜ ·fi ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈ-Û˘-·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ Î·È ËÛ˘Û¯¤ÙÈÛË Ù˘ Û˘ÌÌfiÚʈÛ˘ Ì ‰È¿ÊÔÚÔ˘˜ ·Ú¿-ÁÔÓÙ˜ fiˆ˜ Ë ËÏÈΛ·, ÙÔ Ê‡ÏÔ, Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ·Ù˘ ·ÔÛȉ‹ÚˆÛ˘, ÙÔ Û‡ÓÔÏÔ ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·-ÙÔ˜, Ë ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂÙ¿ÁÁÈ-ÛË Î·È Ë ÊÂÚÚÈÙ›ÓË ÙÔ˘ ÔÚÔ‡.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ªÂÏÂÙ‹ıËÎ·Ó 90 ·È‰È¿ Ô˘ ¿Û¯Ô˘Ó ·fi ÔÌfi˙˘ÁË ‚-ª∞

(48 ·ÁfiÚÈ· Î·È 42 ÎÔÚ›ÙÛÈ·) ËÏÈΛ·˜ 3-18 ¯ÚfiÓˆÓ (̤ÛË ËÏÈ-Λ·: 12,3±4,4 ¤ÙË). OÈ ·ÛıÂÓ›˜ ‚Ú›ÛÎÔÓÙ·Ó Û ٷÎÙÈÎfi Úfi-ÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘-·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘,Ì ÔÈΛÏË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË. ™Â fiÏÔ˘˜ ÙÔ˘˜·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘, Ë ·ÔÛȉ‹ÚˆÛË ¤ÁÈÓ Ì ˘Ô‰fiÚÈ· ¤Á-¯˘ÛË Ù˘ ‰ÂÛÊÂÚÈÔÍ·Ì›Ó˘ ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ·fi ÙÔ˘ÛÙfiÌ·ÙÔ˜ ıÂڷ›·˜ Ì deferiprone (L1).

OÈ ¿Û¯ÔÓÙ˜ ¯ˆÚ›ÛÙËÎ·Ó Û ÙÚÂȘ ÔÌ¿‰Â˜, ·Ó¿ÏÔÁ· ÌÂÙËÓ ËÏÈΛ·: Ë ÔÌ¿‰· ∞ (¡=27 ·ÛıÂÓ›˜) ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂ-Ó›˜ ËÏÈΛ·˜ 3-10 ̄ ÚfiÓˆÓ, Ë ÔÌ¿‰· µ (¡=26 ·ÛıÂÓ›˜) ËÏÈΛ·˜

10-15 ¯ÚfiÓˆÓ Î·È Ë ÔÌ¿‰· ° (¡=37 ·ÛıÂÓ›˜) ÂÚÈÂÏ¿Ì‚·Ó·ÛıÂÓ›˜ ËÏÈΛ·˜ 15-18 ¯ÚfiÓˆÓ.

ø˜ ÚÔ˜ ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË, ÔÈ ¿Û¯Ô-ÓÙ˜ ¯ˆÚ›ÛÙËηÓ, ›Û˘, Û ÙÚÂȘ ÔÌ¿‰Â˜: Ë 1Ë ÔÌ¿‰· Â-ÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì η΋ Û˘ÌÌfiÚʈÛË (·ÔÛȉ‹ÚˆÛË<4 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·), Ë 2Ë ÔÌ¿‰· ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂ-Ó›˜ Ì ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË (·ÔÛȉ‹ÚˆÛË 4-5 ÊÔÚ¤˜ ÙËÓ‚‰ÔÌ¿‰·) Î·È Ë 3Ë ÔÌ¿‰· ·ÛıÂÓ›˜ Ì ηϋ Û˘ÌÌfiÚʈÛË(·ÔÛȉ‹ÚˆÛË 5-6 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·).

∞fi ÙÔÓ ·ÙÔÌÈÎfi Ê¿ÎÂÏÔ ÙÔ˘ οı ·ÛıÂÓ‹, ηٷÁÚ¿ÊËÎÂÔ Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·ÁÁ›ÛÂˆÓ (ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜), Ô̤ÛÔ˜ fiÚÔ˜ ÙˆÓ ÙÈÌÒÓ ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ 5 ¯ÚfiÓˆÓ Ù˘ ·ÈÌÔ-ÛÊ·ÈÚ›Ó˘ Î·È Ù˘ ÊÂÚÚÈÙ›Ó˘ Î·È Ë ‰È¿ÚÎÂÈ· Ù˘ ıÂڷ›·˜·ÔÛȉ‹ÚˆÛ˘.

∏ ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË ¤ÁÈÓ Ì ÙË ‚Ô‹ıÂÈ· ËÏÂÎÙÚÔÓÈÎÔ‡˘ÔÏÔÁÈÛÙ‹ Î·È Ë ÂÊ·ÚÌÔÁ‹ ÙˆÓ ‚ÈÔÛÙ·ÙÈÛÙÈÎÒÓ ‰ÔÎÈÌ·ÛÈÒÓÌ ÙË ¯Ú‹ÛË ÙˆÓ ·Î¤ÙˆÓ SPSS for Windows ’95 Î·È StatCalcÙÔ˘ Epilnfo 2000.

∏ ‰È·‰Èηۛ· Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ·Ó¿Ï˘Û˘ ÂÚÈÂÏ¿Ì‚·Ó¢ÔÏÔÁÈÛÌfi ÁÈ· οı ÌÂÙ·‚ÏËÙ‹ Ù˘ ̤Û˘ ÙÈÌ‹˜ (n) Î·È ÙË˜Ù˘È΋˜ ·fiÎÏÈÛ˘ (SD). °È· ÙÔÓ ¤ÏÂÁ¯Ô ‚ÈÔÛÙ·ÙÈÛÙÈÎÒÓ˘Ôı¤ÛˆÓ, ÂÊ·ÚÌfiÛÙËÎÂ Ë ·Ó¿Ï˘ÛË ‰È·Î‡Ì·ÓÛ˘(Analysis of Variance-ANOVA). ∂›Û˘, ˘ÔÏÔÁ›ÛÙËÎ·Ó ÔÈÛ˘ÓÙÂÏÂÛÙ¤˜ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ Î·È ÂϤÁ¯ıËÎÂ Ë ÛÙ·ÙÈÛÙÈ΋ÛËÌ·ÓÙÈÎfiÙËÙ· ÙˆÓ Û˘ÓÙÂÏÂÛÙÒÓ r, ηٿ ÂÚ›ÙˆÛË. ∆¤ÏÔ˜,ÁÈ· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ·ÓÂÍ·Úًو˜ Û¯ÂÙÈ˙fiÌÂÓˆÓ ÌÂ-Ù·‚ÏËÙÒÓ Ì ÙË ÊÂÚÚÈÙ›ÓË, ÂÊ·ÚÌfiÛÙËÎ·Ó ÌÔÓ٤Ϸ ÔÏÏ·-Ï‹˜ Û˘Û¯¤ÙÈÛ˘ (4).

∞ÔÙÂϤÛÌ·Ù·O ̤ÛÔ˜ fiÚÔ˜ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂ-

Ù¿ÁÁÈÛË, Ô Ì¤ÛÔ˜ fiÚÔ˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÙÔ˘ ÔÚÔ‡, ÔÛ˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜ Î·È Ë ¯ÚÔ-ÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘ Û οı ÔÌ¿‰··ÛıÂÓÒÓ ÂÚÈÁÚ¿ÊÔÓÙ·È ·Ó·Ï˘ÙÈο ÛÙÔÓ ¶›Ó·Î· 1.

∞fi ÙË ÌÂϤÙË Ù˘ Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ·ÔÛÈ-‰‹ÚˆÛË, ‰È·ÈÛÙÒıËÎ·Ó Ù· ÂÍ‹˜: η΋ Û˘ÌÌfiÚʈ-ÛË Â›¯·Ó 11 ·ÛıÂÓ›˜ (2 ·fi ÙËÓ ÔÌ¿‰· ∞, 2 ·fi ÙËÓÔÌ¿‰· µ Î·È 7 ·fi ÙËÓ ÔÌ¿‰· °), ̤ÙÚÈ· Û˘ÌÌfiÚ-ʈÛË Â›¯·Ó 20 ·ÛıÂÓ›˜ (3 ·fi ÙËÓ ÔÌ¿‰· ∞, 6 ·fi

∞fi ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Û˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÔÈ ¿-Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷ-ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘ Î·È ·ÔÛȉ‹ÚˆÛ˘·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ¤¯Ô˘Ó ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔÔÛÔÛÙfi ηϋ Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË. ∏¤ÁηÈÚË ¤Ó·ÚÍË Ù˘ ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ÚÒÙ˷ȉÈ΋ ËÏÈΛ· ‰ÂÓ ÚÔÊ˘Ï¿ÛÛÂÈ ÌfiÓÔ ·fi ÙËÓ˘ÂÚÊfiÚÙˆÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ Ì ۛ‰ËÚÔ, ·ÏÏ¿Û˘Ó¿ÁÂÙ·È Î·È Î·Ï‡ÙÂÚË Û˘ÌÌfiÚʈÛË.

§¤ÍÂȘ ÎÏÂȉȿ: ÔÌfi˙˘ÁË ‚-ª∞, ·ÔÛȉ‹ÚˆÛË, Û˘Ì-ÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË.

of compliance. The authors believe that earlyintroduction of chelation will not only have a directeffect on iron overload, but will also lead tocontinued good compliance.

Key words: beta-thalassaemia major, chelationtherapy, compliance.

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ÙËÓ ÔÌ¿‰· µ Î·È 11 ·fi ÙËÓ ÔÌ¿‰· °) Î·È Î·Ï‹ Û˘Ì-ÌfiÚʈÛË Â›¯·Ó 59 ·ÛıÂÓ›˜ (22 ·fi ÙËÓ ÔÌ¿‰· ∞,18 ·fi ÙËÓ ÔÌ¿‰· µ Î·È 19 ·fi ÙËÓ ÔÌ¿‰· °) (¶›-ӷη˜ 2).

∞fi ÙȘ Û˘Û¯ÂÙ›ÛÂȘ ÙˆÓ ‰È·ÊfiÚˆÓ ·Ú·Ì¤ÙÚˆÓˆ˜ ÚÔ˜ ÙË Û˘ÌÌfiÚʈÛË, ÚԤ΢„ fiÙÈ Ë Û˘Ì-ÌfiÚʈÛË ÌÂÈÒÓÂÙ·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο fiÛÔ ·˘-Í¿ÓÂÙ·È Ë ËÏÈΛ· (p<0,05), Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘·ÔÛȉ‹ÚˆÛ˘ (p<0,01) Î·È Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·Á-Á›ÛÂˆÓ (ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜) (p<0,05) (¶›Ó·Î˜ 2 ηÈ3, ∂ÈÎfiÓ· 1).

ŸÛÔÓ ·ÊÔÚ¿ ÛÙË ÊÂÚÚÈÙ›ÓË, Ê·›ÓÂÙ·È fiÙÈ ÔÈ ¿-Û¯ÔÓÙ˜ Ô˘ ›¯·Ó η΋ Î·È Ì¤ÙÚÈ· Û˘ÌÌfiÚʈÛË›¯·Ó ÈÔ ˘„ËϤ˜ ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘ (ÂÚ›Ô˘ ›‰È˜ÙÈ̤˜ ÛÙȘ ‰‡Ô ÚÒÙ˜ ÔÌ¿‰Â˜), ÂÓÒ fiÛÔÈ Â›¯·Ó η-Ï‹ Û˘ÌÌfiÚʈÛË Â›¯·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ¯·ÌË-ÏfiÙÂÚ˜ ÙÈ̤˜ (p<0,01) (¶›Ó·Î·˜ 3 Î·È ∂ÈÎfiÓ· 2).

∏ ̤ÛË ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂ-Ù¿ÁÁÈÛË ÔÈΛÏÏÂÈ ˆ˜ ÚÔ˜ ÙË Û˘ÌÌfiÚʈÛË, Ì ‰È·-ÊÔÚ¤˜ ÛÙ·ÙÈÛÙÈο ÌË ÛËÌ·ÓÙÈΤ˜ (p=0,48).

ŸÛÔÓ ·ÊÔÚ¿ ÛÙÔ Ê‡ÏÔ, ÛÙËÓ 1Ë ÔÌ¿‰· (Ì η-΋ Û˘ÌÌfiÚʈÛË) ˘ÂÚÙÂÚÔ‡Ó Ù· ·ÁfiÚÈ·, ·ÏÏ¿ ÔȉȷÊÔÚ¤˜ Â›Ó·È ÛÙ·ÙÈÛÙÈο ÌË ÛËÌ·ÓÙÈΤ˜ (p=0,58)(¶›Ó·Î·˜ 2).

™ÙËÓ ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË Ô˘ ¤ÁÈÓ ÁÈ·ÙË ÌÂϤÙË Ù˘ Û˘Û¯¤ÙÈÛ˘ ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÊÂÚ-

ÚÈÙ›Ó˘ Ì ÙÔ Ê‡ÏÔ, ÙËÓ ËÏÈΛ·, ÙËÓ ÙÈÌ‹ Ù˘ Hb ÚÈÓ·fi ÙË ÌÂÙ¿ÁÁÈÛË, ÙȘ ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ Î·È ÙË Û˘Ì-ÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË, ‰È·ÈÛÙÒıËΠfiÙÈ˘¿Ú¯ÂÈ Û˘Û¯¤ÙÈÛË Ù˘ ÙÈÌ‹˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÌfiÓÔÌ ÙËÓ ·ÔÛȉ‹ÚˆÛË Î·È Ë ‰È·ÊÔÚ¿ Â›Ó·È ÛÙ·ÙÈÛÙÈ-ο ÛËÌ·ÓÙÈ΋ (p<0,001).

™˘˙‹ÙËÛË OÈ Ù·ÎÙÈΤ˜ ÌÂÙ·ÁÁ›ÛÂȘ ÛÙËÓ ÔÌfi˙˘ÁË ‚-ª∞ η-

Ù·ÛÙ¤ÏÏÔ˘Ó ÙËÓ ÂÍˆÌ˘ÂÏÈ΋ ÂÚ˘ıÚÔÔ›ËÛË Î·ÈÚÔÊ˘Ï¿ÛÛÔ˘Ó ·fi ÙËÓ ÂÌÊ¿ÓÈÛË ÛÔ‚·Ú‹˜ ·Ó·È-Ì›·˜ (5). ŸÌˆ˜, Ë ·˘ÍË̤ÓË ÚfiÛÏË„Ë Ûȉ‹ÚÔ˘·fi ÙȘ Ù·ÎÙÈΤ˜ ÌÂÙ·ÁÁ›ÛÂȘ ‰È·Ù·Ú¿ÛÛÂÈ ÙÔÓ ÌÂ-Ù·‚ÔÏÈÛÌfi ÙÔ˘ Î·È Ô‰ËÁ› Û ÏÂfiÓ·ÛÌ· Ûȉ‹ÚÔ˘,ÙÔ ÔÔ›Ô ÂÓ·ÔÙ›ıÂÙ·È Û fiÏÔ˘˜ ÙÔ˘˜ ÈÛÙÔ‡˜ ηÈÔ‰ËÁ› Û ÚÔ˚Ô‡Û· ›ÓˆÛË Î·È ÏÂÈÙÔ˘ÚÁÈ΋ ·ÓÂ-¿ÚÎÂÈ· ÙˆÓ ‰È·ÊfiÚˆÓ ÔÚÁ¿ÓˆÓ (6).

∏ ¤ÁηÈÚË ¤Ó·ÚÍË Ù˘ ·ÔÛȉ‹ÚˆÛ˘ ÂÚÈÔÚ›-˙ÂÈ ÙËÓ ·ÚÂÁ¯˘Ì·ÙÈ΋ ‚Ï¿‚Ë ÙˆÓ ‰È·ÊfiÚˆÓ ÔÚÁ¿-ÓˆÓ, ‰ÈfiÙÈ ÚÔηÏ› ·ÚÓËÙÈÎfi ÈÛÔ˙‡ÁÈÔ Ûȉ‹ÚÔ˘ ηÈÌ›ˆÛË ÙˆÓ ·ÔıÂÌ¿ÙˆÓ ÙÔ˘ Ûȉ‹ÚÔ˘ ÙˆÓ ÈÛÙÒÓ(7-10).

∏ Û˘ÌÌfiÚʈÛË ÛÙË ıÂڷ›· ·ÔÛȉ‹ÚˆÛ˘ÛÙËÓ ÔÌfi˙˘ÁË ‚-ª∞ ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙË Ì›-ˆÛË ÙˆÓ ÂÈÏÔÎÒÓ Ù˘ ÓfiÛÔ˘ (11). ∆· ÙÂÏÂ˘Ù·›·¯ÚfiÓÈ·, ˘¿Ú¯Ô˘Ó Ï›Á˜ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ó·ÊÔÚ¤˜

¶›Ó·Î·˜ 1. ∞ÈÌ·ÙÔÏÔÁÈΤ˜ ·Ú¿ÌÂÙÚÔÈ, Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÌÂÙ·ÁÁ›ÛÂˆÓ Î·È ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘ ÙˆÓ ·Û¯fi-ÓÙˆÓ ·fi ‚-ª∞, ·Ó¿ ÔÌ¿‰· ËÏÈΛ·˜

OÌ¿‰· º‡ÏÔ ∏b ºÂÚÚÈÙ›ÓË MÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ ∞ÔÛȉ‹ÚˆÛË∞ ∫ ª¤ÛË ÙÈÌ‹ (g/dl) ª¤ÛË ÙÈÌ‹ (ng/ml) (n) (Ì‹Ó˜)

∞ 14 13 9,467 1494,07 18-200 3-90µ 14 12 9,678 2115 85-440 30-138° 20 17 9,763 2378,97 105-518 60-192

Hb: ·ÈÌÔÛÊ·ÈÚ›ÓË

¶›Ó·Î·˜ 2. ª¤ÛË ÙÈÌ‹ Î·È Ù˘È΋ ·fiÎÏÈÛË Ù˘ ËÏÈΛ·˜ ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞, Û ۯ¤ÛË Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛÈ-‰‹ÚˆÛË

™˘ÌÌfiÚʈÛË ∞ÚÈıÌfi˜ ·Û¯fiÓÙˆÓ OÌ¿‰Â˜ ∏ÏÈΛ· (¯ÚfiÓÈ·)∞Á. ∫. ™‡ÓÔÏÔ ∞ µ ° ª¤ÛË ÙÈÌ‹ ∆˘È΋ ·fiÎÏÈÛË p

∫·Î‹ 7 4 11 2 2 7 14,55 3,57 <0,05ª¤ÙÚÈ· 9 11 20 3 6 11 13,68 3,48 <0,05∫·Ï‹ 32 27 59 22 18 19 11,13 4,62 <0,05

∞Á.: ·ÁfiÚÈ· ∫.: ÎÔÚ›ÙÛÈ·

¶›Ó·Î·˜ 3. ª¤ÛË ÙÈÌ‹ Î·È Ù˘È΋ ·fiÎÏÈÛË Ù˘ ¯ÚÔÓÈ΋˜ ‰È¿ÚÎÂÈ·˜ Ù˘ ·ÔÛȉ‹ÚˆÛ˘, ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜ Î·È Ù˘ ÙÈÌ‹˜ Ù˘ÊÂÚÚÈÙ›Ó˘ ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞, Û ۯ¤ÛË Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË

™˘ÌÌfiÚʈÛË∫·Î‹ ª¤ÙÚÈ· ∫·Ï‹ p

∞ÔÛȉ‹ÚˆÛË (Ì‹Ó˜) 134,16±47,04 124,8±36,24 89,64±57,72 <0,01ªÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ 349±130,61 304±106,65 230,62±154,63 <0,05ºÂÚÚÈÙ›ÓË (ng/ml) 2409,9±1132,35 2488,5±823,84 1792,2±765,99 <0,01

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Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ·ÛıÂÓ›˜ Ô˘ ¿Ú¯ÈÛ·Ó ·ÔÛÈ-‰‹ÚˆÛË ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ (12,13).

™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, fiÏÔÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fiÔÌfi˙˘ÁË ‚-ª∞ ‚Ú›ÛÎÔÓÙ·Ó Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ·ÌÂÙ¿ÁÁÈÛ˘ Î·È ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ÓfiÛÔ˘ Î·È ‰È·ÈÛÙÒıËΠfiÙÈ ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔ-ÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Â›¯Â ηϋ ¤ˆ˜ ̤ÙÚÈ· Û˘ÌÌfiÚ-ʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (88%). ™Â ‰‡Ô ÌÂϤÙÂ˜Ô˘ ¤ÁÈÓ·Ó Û ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¿Ú¯ÈÛ·Ó ·ÔÛȉ‹-ÚˆÛË ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ‰È·ÈÛÙÒıËΠfiÙÈÙÔ ÔÛÔÛÙfi Ù˘ Û˘ÌÌfiÚʈÛ˘ ‹Ù·Ó <70%, ÂÓÒ ÔÈ·ÛıÂÓ›˜ Ô˘ Û˘ÌÌÔÚÊÒıËÎ·Ó Û ÌÈÎÚfiÙÂÚÔ Ô-ÛÔÛÙfi ‹Ù·Ó Û˘Ó‹ıˆ˜ ÌÂÁ·Ï‡ÙÂÚ˘ ËÏÈΛ·˜ (2,8).

∏ ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ÌÂϤÙ˘ Ì·˜ ·Ú·ÙËÚ‹ıËΠ̠ÙËÓ ·‡ÍËÛË Ù˘ËÏÈΛ·˜ ηÈ, Ê˘ÛÈο, ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ¯ÔÚËÁÔ‡ÌÂ-ÓˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜. ∞fi ÙË ÌÂϤÙË ÙˆÓ ËÏÈÎÈÒÓÊ¿ÓËΠfiÙÈ ÚfiÎÂÈÙ·È ÁÈ· ·È‰È¿ Ù˘ ÂÊË‚È΋˜ ËÏÈ-Λ·˜, Ù· ÔÔ›· Û ÌÂÁ¿ÏÔ ‚·ıÌfi ·ÚÔ˘ÛÈ¿˙Ô˘Ó „˘-¯ÔÏÔÁÈΤ˜ ·ÓÙȉڿÛÂȘ ÏfiÁˆ Ù˘ ¯ÚÔÓÈfiÙËÙ·˜ ÙÔ˘ÓÔÛ‹Ì·ÙÔ˜ Î·È Ù˘ ¯ÚÔÓÔ‚fiÚÔ˘ ‰È·‰Èηۛ·˜ Ù˘·ÔÛȉ‹ÚˆÛ˘. °È· ÙÔÓ ÏfiÁÔ ·˘Ùfi, ·ÚÎÂÙ¿ ·fi ·˘-Ù¿ Ù· ·È‰È¿ ¯ÚÂÈ¿ÛÙËÎ·Ó „˘¯ÔÏÔÁÈ΋ ˘ÔÛÙ‹ÚÈÍË.∫·È ˆ˜ ÚÔ˜ ÙËÓ ËÏÈΛ·, Ù· Â˘Ú‹Ì·Ù· Ù˘ ·ÚÔ‡-Û·˜ ÌÂϤÙ˘ Û˘ÌʈÓÔ‡Ó Ì ٷ Â˘Ú‹Ì·Ù· ÌÂÏÂÙÒÓÔ˘ ÚԷӷʤÚıËÎ·Ó (2,8). ™Â Ì›· ·Ó·‰ÚÔÌÈ΋ ÌÂ-ϤÙË ÙˆÓ Richardson Î·È Û˘Ó (14), ‚Ú¤ıËΠ›Û˘fiÙÈ Ë Û˘ÌÌfiÚʈÛË Â›Ó·È ·ÓÙÈÛÙÚfiʈ˜ ·Ó¿ÏÔÁË ÌÂÙËÓ ËÏÈΛ· ¤Ó·Ú͢ Ù˘ ·ÔÛȉ‹ÚˆÛ˘.

ŸÛÔÓ ·ÊÔÚ¿ ÛÙÔ Ê‡ÏÔ ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ·-ÚÔ‡Û·˜ ÌÂϤÙ˘, ·Ú·ÙËÚ‹ıËΠfiÙÈ Ù· ·ÁfiÚÈ·¤¯Ô˘Ó ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË ·fi Ù· ÎÔÚ›ÙÛÈ·.∫·È ÛÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹, ÂÚfiÎÂÈÙÔ ÁÈ· ·ÁfiÚÈ·

ÂÊË‚È΋˜ ËÏÈΛ·˜, Ù· ÔÔ›· Èı·ÓfiÓ ÏfiÁˆ ÔÚÌÔÓÈ-ÎÒÓ ÌÂÙ·‚ÔÏÒÓ Á›ÓÔÓÙ·È ÈÔ ·ÚÔÚÌËÙÈο Î·È ·ÓÙÈ-‰Ú·ÛÙÈο ·fi Ù· ÎÔÚ›ÙÛÈ·.

¢È·ÈÛÙÒıËÎÂ, ›Û˘, fiÙÈ Ë ÔÌ¿‰· ·ÛıÂÓÒÓ ÌÂηχÙÂÚË Û˘ÌÌfiÚʈÛË ·ÚÔ˘ÛÈ¿˙ÂÈ ¯·ÌËÏfiÙÂÚ˜ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘. ∆· Â˘Ú‹Ì·Ù· Ù˘ ·ÚÔ‡Û·˜ ÌÂ-ϤÙ˘ Û˘ÌʈÓÔ‡Ó, ›Û˘, Ì ÙË ÌÂϤÙË ÙˆÓMaurer Î·È Û˘Ó (8), ηıÒ˜ ›Û˘ Î·È Ì ÙË ÌÂϤÙËÙˆÓ ∫·ÙÙ¿ÌË Î·È Û˘Ó (15), ÛÙËÓ ÔÔ›· ‰È·ÈÛÙÒıË-ΠÙËÓ ÙÂÏÂ˘Ù·›· 15ÂÙ›· Ì›ˆÛË ÙˆÓ ÙÈÌÒÓ Ù˘ ÊÂÚ-ÚÈÙ›Ó˘ ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞ Î·È ‚ÂÏÙ›ˆÛË ÙË˜Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ·ÔÛȉ‹ÚˆÛË.

™˘ÌÂÚ·ÛÌ·ÙÈο, ·fi ÙËÓ ·ÚÔ‡Û· ÌÂϤÙËÚÔ·ÙÂÈ fiÙÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ Ô˘‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘ ηȷÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ¤¯Ô˘ÓÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi Û¯ÂÙÈο ηϋ Û˘ÌÌfiÚ-ʈÛË ÛÙË ıÂڷ›· ·ÔÛȉ‹ÚˆÛ˘.

∂ÎÙfi˜ fï˜ ·fi ÙË Û˘ÌÌfiÚʈÛË, ÛËÌ·ÓÙÈÎfiÚfiÏÔ Ê·›ÓÂÙ·È Ó· ·›˙ÂÈ Î·È Ë ËÏÈΛ· ¤Ó·Ú͢ Ù˘·ÔÛȉ‹ÚˆÛ˘. ∏ ¤Ó·ÚÍ‹ Ù˘ ·fi ÙËÓ ÚÒÙË ·È-‰È΋ ËÏÈΛ· ‰ÂÓ ÚÔÊ˘Ï¿ÛÛÂÈ ÌfiÓÔ ·fi ÙËÓ ˘ÂÚ-ÊfiÚÙˆÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ Ì ۛ‰ËÚÔ, ·ÏÏ¿ Û˘ÓÂ-¿ÁÂÙ·È Î·È Î·Ï‡ÙÂÚË Û˘ÌÌfiÚʈÛË.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Vecchio C, Derchi G. Management of cardiac complications

in patients with thalassemia major. Semin Hematol1995;32:288-296.

2. Olivieri NF, Brittenham GM. Iron-chelating therapy and thetreatment of thalassemia. Blood 1997;89:739-761.

3. µuja LM, Roberts WC. Iron in the heart. Etiology and clinicalsignificance. Am J Med 1971;51:209-221.

4. Armitage P, Berry G. Statistical methods in medicalresearch. 2nd ed. Oxford: Blackwell Scientific Publications;1989.

5. Fosburg MT, Nathan DG. Treatment of Cooley’s anemia.Blood 1990;76:435-444.

∂ÈÎfiÓ· 1. ª¤Û˜ ÙÈ̤˜ Ù˘ ËÏÈΛ·˜, Ù˘ ¯ÚÔÓÈ΋˜ ‰È¿ÚÎÂÈ·˜ Ù˘·ÔÛȉ‹ÚˆÛ˘ Î·È ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜ Û ۯ¤ÛË Ì ÙË Û˘Ì-ÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (η΋, ̤ÙÚÈ·, ηϋ).

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HÏÈΛ· (Ì‹Ó˜)

ÃÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ·ÔÛȉ‹ÚˆÛ˘ (Ì‹Ó˜)

ªÔÓ¿‰Â˜ ·›Ì·ÙÔ˜

∫·Î‹ ª¤ÙÚÈ· ∫·Ï‹

∂ÈÎfiÓ· 2. ª¤Û˜ ÙÈ̤˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ Û ۯ¤ÛË Ì ÙË Û˘ÌÌfiÚ-ʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (η΋, ̤ÙÚÈ·, ηϋ).

3000

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2000

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6. Giardina PJ, Grady RW. Chelation therapy in beta-thalassemia: the benefits and limitations of desferrioxamine.Semin Hematol 1995;32:304-312.

7. Weatherall DJ, Clegg JB. The thalassaemic syndromes. 3rded. Oxford: Blackwell Scientific Publications; 1981.

8. Maurer HS, Lloyd-Still JD, Ingrisano C, Gonzalez-Crussi F,Honig GR. A prospective evaluation of iron chelationtherapy in children with severe beta-thalassemia. A six-yearstudy. Am J Dis Child 1988;142:287-292.

9. Giardina PJ, Grady RW, Ehlers KH, Burstein S, Graziano JH,Markenson AL et al. Current therapy of Cooley’s anemia. Adecade of experience with subcutaneous desferrioxamine.Ann NY Acad Sci 1990;612:275-285.

10. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP,McGee A et al. Survival in medically treated patients withhomozygous beta-thalassemia. N Engl J Med1994;331:574-578.

11. Cohen A, Martin M, Schwartz E. Response to long-termdeferoxamine therapy in thalassemia. J Pediatr1981;99:689-694.

12. Borgna-Pignatti C, Piga A, Rugolotto S, De Stefano P, DiPalma AM, Gamberini R et al. Survival and diseasecomplications in thalassemia major. Bone MarrowTransplant 1997;19 (Suppl 2):S16-S17.

13. Ladis V, Papadopoulou A, Athanassaki C, Palamidou F,

Kostaridou S, Berdousi E et al. Long term survival andcauses of death in patients with thalassemia underconventional treatment. Bone Marrow Transplant 1997;19(Suppl 2):S4-S6.

14. Richardson ME, Matthews RN, Alison JF, Menahem S,Mitvalsky J, Byrt E et al. Prevention of heart disease bysubcutaneous desferrioxamine in patients withthalassaemia major. Aust NZ J Med 1993;23:656-661.

15. Kattamis AC, Dinopoulos A, Ladis V, Athanassaki K,Palamidou F. Changing pattern in ferritin levels amongtransfused patients with thalassemia on desferrioxamine ina period of 15 years. Proceedings of the 7th InternationalConference of thalassemia and haemoglobinopathies.Bangkok Thailand; 1999 May 31-June 4; p. 272.

∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 20-09-2002 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 07-02-2003

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∫˘Úȷ΋ ¶··‰ÔÔ‡ÏÔ˘-§ÂÁ̤ÏÔ˘ º›Ï˘ÚÔ, ∆.∫. 570 10, £ÂÛÛ·ÏÔÓ›ÎË E-mail: legbelos@hol.gr

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™‡Ó‰ÚÔÌÔ Nail-Patella (ÔÛÙÂÔ-ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·). ¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘π. π. πÁÓ·ÙÈ¿‰Ë˜, ª. ∑. °Ô˘‰ÂÛ›‰Ô˘, ∞. §. ¶··‰ÔÔ‡ÏÔ˘, ∫. ∆ÛÔ˘Ì¿Î·˜

Nail-Patella syndrome. A case reportJ. J. Ignatiadis, M. Z. Goudesidou, A. L. Papadopoulou, C. Tsoumakas

∂¡¢π∞º∂ƒOÀ™∞ ¶∂ƒπ¶∆ø™∏ CASE REPORT

¶·È‰È·ÙÚÈÎfi ∆Ì‹Ì·, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∫∞∆, ∞ÙÙÈ΋ Pediatric Department, KAT General Hospital, Attiki

�¶ÂÚ›ÏË„Ë: ∆Ô Û‡Ó‰ÚÔÌÔ Nail-Patella (NPS) Û˘Ó-‰˘¿˙ÂÈ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ, ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·,Ï·ÁÒÓȘ ÂÍÔÛÙÒÛÂȘ Î·È Û˘ÁÁÂÓ‹ Û‡Áη̄˷ÁÎÒÓˆÓ. ™˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ ÓÂÊÚÔ¿ıÂÈ· ÌÂ Û˘Á-ÁÂÓ›˜ ‰È·Ì·Úٛ˜ Ô˘ÚÔÔÈËÙÈÎÔ‡, ÔÊı·ÏÌÈΤ˜ ·Óˆ-̷ϛ˜ Î·È ÓfiÛÔ˜ Goodpasture. ∫ÏËÚÔÓÔÌÂ›Ù·È Ì·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú· Î·È ÔÊ›-ÏÂÙ·È Û ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ LMX1B Ô˘ ¤¯Âȯ·ÚÙÔÁÚ·ÊËı› ÚfiÛÊ·Ù· ÛÙÔ ¯ÚˆÌfiۈ̷ 9 ÛÙËÓÙ·ÈÓ›· q34.1. ∫ÔÚ›ÙÛÈ ËÏÈΛ·˜ 4 ¯ÚfiÓˆÓ ÚÔÛ‹ÏıÂÁÈ· ¤ÏÂÁ¯Ô ÏfiÁˆ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·˜. ™ÙËÓ ÎÏÈÓÈ΋ÂͤٷÛË Î·È ÛÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô Ô˘ ·ÎÔ-ÏÔ‡ıËÛÂ, ÏËÓ Ù˘ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·˜, ‰È·ÈÛÙÒıË-Î·Ó ÂÈϤÔÓ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ, Ï·ÁfiÓȘ ÂÍÔ-ÛÙÒÛÂȘ Î·È Û‡ÁÎ·Ì„Ë ÙˆÓ ·ÁÎÒÓˆÓ. ∆Ô ·ÙÔÌÈÎfi·Ó·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ, ÂÓÒ ÛÙÔ ÔÈÎÔÁÂÓÂÈ·ÎfiÈÛÙÔÚÈÎfi, Ë ÌËÙ¤Ú· Ù˘ ·ÛıÂÓÔ‡˜ ›¯Â ˘Ô‚ÏËı›Û ¤̂·ÛË Û ËÏÈΛ· 17 ¯ÚfiÓˆÓ ÏfiÁˆ Û‡ÁηÌ-„˘ ·ÁÎÒÓˆÓ. O ·‰Úfi˜ ‚ÈÔ¯ËÌÈÎfi˜, Ô ÂÓ‰Âϯ‹˜¤ÏÂÁ¯Ô˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙÔ˘ ÌÂÙ·‚Ô-ÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ Î·È Ô ¤ÏÂÁ¯Ô˜ ÁÈ· Û˘ÛÙËÌ·-ÙÈ΋ ÓfiÛÔ ‹Ù·Ó ·ÚÓËÙÈÎÔ›. ∏ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËÎÂÛ ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË ÁÈ· ·ÔηٿÛÙ·ÛË ÙˆÓ·ÁÎÒÓˆÓ Ì ÈηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù·. ∏ ·Ô˘-Û›· ÂÈÁÔÓ·Ù›‰ˆÓ ‰ÂÓ ‰ËÌÈÔ˘ÚÁ› ÚÔ‚Ï‹Ì·Ù· ·Ó·-ËÚ›·˜. ∏ ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È Ë ¯ÂÈÚÔ˘ÚÁÈ΋·ÔηٿÛÙ·ÛË ÚÔÛʤÚÔ˘Ó ÛÙÔ˘˜ ·ÛıÂÓ›˜ Û¯Â-‰fiÓ Ê˘ÛÈÔÏÔÁÈ΋ ˙ˆ‹. ∞·ÈÙ›ٷÈ, fï˜, Û˘¯Ófi˜¤ÏÂÁ¯Ô˜ ÁÈ· ÙÔ ÂӉ¯fiÌÂÓÔ Û˘ÛÙËÌ·ÙÈÎÒÓ ÂΉËÏÒ-ÛˆÓ. O ÚÔÁÂÓÓËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ›-Ó·È ÂÊÈÎÙfi˜, Ë ÙÂÎÓÔÔ›ËÛË fï˜ ·Ôı·ÚÚ‡ÓÂÙ·È΢ڛˆ˜ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ ÛÔ‚·Ú‹˜ ÓÂÊÚÈ΋˜ ‚Ï¿‚˘.

§¤ÍÂȘ ÎÏÂȉȿ: Nail-Patella, Turner-Kieser, Û‡ÁηÌ-„Ë ·ÁÎÒÓˆÓ, ÔÓ˘¯Ô‰˘ÛÏ·Û›·.

�Abstract: Nail-Patella syndrome (NPS) is a rareautosomal dominant disorder associated withonychodysplasia, antecubital pterygium, hypoplasiaor absent patellae, and iliac horns. Nephropathy isoften associated with genetic anomalies of theurinary tract, ophthalmic disorders andGoodpasture syndrome. It is the result of a mutationin LMX1B gene, recently mapped in the 9q34.1chromosomal locus. A 4-year old girl presented withonychodysplasia which on clinical and radiologicalexamination was associated with bilateralantecubital pterygium and absence of patellae. Herprevious medical history was insignificant but hermother had a history of antecubital pterygium forwhich she was operated, during adolescence. Thegirl’s renal and liver function, and her calciummetabolism were normal. No laboratory evidence ofsystematic disease was found. She was operatedwith satisfactory results. Absence of patellae doesnot cause any disability. The early diagnosis andsurgical correction helps patients lead a normal life,nevertheless, frequent tests for systematiccomplications are needed. Prenatal diagnosis ispossible today but childbearing is discouragedmainly because of renal complications.

Key words: Nail-Patella, Turner-Kieser, antecubitalpterygium, onychodysplasia.

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™˘ÓÙÔÌÔÁڷʛ˜¡PS ™‡Ó‰ÚÔÌÔ ¡ail-Patella BM™ µ·ÛÈ΋ ÌÂÌ‚Ú¿ÓË ÛÂÈÚ¿Ì·ÙÔ˜

∂ÈÛ·ÁˆÁ‹∆Ô Û‡Ó‰ÚÔÌÔ Nail-Patella (NPS) ‹ “Turner-

Kieser”, ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·ÚıÚÔ-ÔÓ˘-¯Ô-ÔÛÙÂÔ‰˘ÛÏ·Û›·, Â›Ó·È ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ ÓfiÛË-Ì·. ™˘Ó‰˘¿˙ÂÈ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·, ȉ›ˆ˜ ÛÙÔ˘˜ ·ÓÙ›-¯ÂÈÚ˜ (·Ï·Û›·, ηٷÎÂÚÌ·ÙÈÛÌfi, ·Ô¯ÚˆÌ·ÙÈ-ÛÌfi) (90%), Û˘ÁÁÂÓ‹ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ (60%),Ï·ÁfiÓȘ ÎÂÚ·ÙfiÌÔÚʘ ÂÍÔÛÙÒÛÂȘ (80%) ηÈÛ˘ÁÁÂÓ‹ Û‡ÁÎ·Ì„Ë ·ÁÎÒÓ· (antecubital pterygium)(1-3). ™˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ ÓÂÊÚÔ¿ıÂÈ·, Û˘ÁÁÂÓ›˜·ÓˆÌ·Ï›Â˜ ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜,ÔÊı·ÏÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Î·È Û‡Ó‰ÚÔÌÔ Goodpasture(4-8).

O Little, ÙÔ 1897 (9), ·Ú’ fiÏÔ Ô˘ ·ÚÔ˘Û›·ÛÂÌfiÓÔ ÙȘ ·ÓˆÌ·Ï›Â˜ Ù˘ ÂÈÁÔÓ·Ù›‰·˜, ıˆÚÂ›Ù·È ÔÚÒÙÔ˜ Ô˘ ÂÚȤÁÚ·„ ÙÔ Û‡Ó‰ÚÔÌÔ, ÂÓÒ Û˘ÓÔ-ÏÈο ̤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÂÚ›Ô˘ 400ÂÚÈÙÒÛÂȘ. ¶ÚfiÎÂÈÙ·È ÁÈ· Û˘ÁÁÂÓ¤˜ ÓfiÛËÌ·, ÎÏË-ÚÔÓÔÌÔ‡ÌÂÓÔ Ì ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·-Ú·ÎÙ‹Ú·, ÔÊÂÈÏfiÌÂÓÔ Û ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘LMX1B ÛÙÔ ¯ÚˆÌfiۈ̷ 9q34.1 (10,11). ¶ÚfiÛÊ·-Ù·, ‰È·ÈÛÙÒıËΠ¿ÏÏË ÌÂÙ¿ÏÏ·ÍË Û ‰È·ÊÔÚÂÙÈÎfiÁÔÓȉ›Ô ˆ˜ ˘Â‡ı˘ÓË ÁÈ· ÙË ÓÂÊÚÔ·ıËÙÈ΋ ÌÔÚÊ‹Ù˘ ÓfiÛÔ˘ (12).

¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘∫ÔÚ›ÙÛÈ ËÏÈΛ·˜ 4 ÂÙÒÓ, ÔÌ·ÎÈ΋˜ ηٷÁˆÁ‹˜,

ÚÔÛ‹Ïı ÛÙ· ∂͈ÙÂÚÈο π·ÙÚ›· ÙÔ˘ ¶·È‰È·ÙÚÈÎÔ‡∆Ì‹Ì·ÙÔ˜ ÙÔ˘ ¡ÔÛÔÎÔÌ›Ԣ ∫∞∆ ÏfiÁˆ ÔÓ˘¯Ô‰˘-ÛÙÚÔÊ›·˜. ¶ÚfiÎÂÈÙ·È ÁÈ· ÙÔ ÌÔÓ·‰ÈÎfi ·È‰› Ê·ÈÓÔ-Ù˘Èο ˘ÁÈÒÓ ÁÔÓ¤ˆÓ. ∏ ·ËÛË, Ô ÙÔÎÂÙfi˜ Î·È Ë Â-ÚÈÁÂÓÓËÙÈ΋ ÂÚ›Ô‰Ô˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. ∆Ô ·ÙÔÌÈ-Îfi ÈÛÙÔÚÈÎfi ‹Ù·Ó ÂχıÂÚÔ. ∞fi ÙÔ ÔÈÎÔÁÂÓÂÈ·ÎfiÈÛÙÔÚÈÎfi ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ë ÌËÙ¤Ú· ·ÚÔ˘Û›·˙ ۇ-

ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ, ÁÈ· ÙËÓ ÔÔ›· ¯ÂÈÚÔ˘ÚÁ‹ıËΠÛÂËÏÈΛ· 17 ÂÙÒÓ, ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ ¿Ìʈ ηÈÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·. ∏ ·‰ÂÏÊ‹ Ù˘ ÌËÙ¤Ú·˜ ·ÚÔ˘-Û›·˙ ÙËÓ ›‰È· ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È ˘Ô‚Ï‹ıËΠÛÙËÓ›‰È· ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË. ¢ÂÓ ·Ó·Ê¤ÚÂÙ·ÈÓÂÊÚÈ΋ ÓfiÛÔ˜ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ·.

™ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË, Ë ·ÛıÂÓ‹˜ ·ÚÔ˘-Û›·˙ ÌÂÚÈ΋ ·Ï·Û›· Î·È Î·Ù·ÎÂÚÌ·ÙÈÛÌfi ÙˆÓ ÔÓ‡-¯ˆÓ Î·È ÛÙÔ˘˜ ‰‡Ô ·ÓÙ›¯ÂÈÚ˜ (∂ÈÎfiÓ· 1) Î·È Û‡-ÁÎ·Ì„Ë ÙˆÓ ·ÁÎÒÓˆÓ Î·Ù¿ 90Ô Ì ·‰˘Ó·Ì›· ¤ÎÙ·-Û˘ (∂ÈÎfiÓ· 2). ∂›¯Â Ê˘ÛÈÔÏÔÁÈ΋ ÎÈÓËÙÈ΋ ÂͤÏÈÍËÎ·È Ô ¤ÏÂÁ¯Ô˜ ÙˆÓ ˘fiÏÔÈˆÓ Û˘ÛÙËÌ¿ÙˆÓ ‹Ù·ÓÊ˘ÛÈÔÏÔÁÈÎfi˜.

ÀÔ‚Ï‹ıËΠ۠ϋÚË ·ÎÙÈÓÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô,ÛÙÔÓ ÔÔ›Ô ‰È·ÈÛÙÒıËÎ·Ó ÂÈϤÔÓ ˘ÔÏ·Û›· Î·È˘ÂÍ¿ÚıÚËÌ· ÎÂÊ·ÏÒÓ ÎÂÚΛ‰ˆÓ (∂ÈÎfiÓ· 3), Ï‹-Ú˘ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ (∂ÈÎfiÓ· 4) Î·È Ï·ÁfiÓȘÂÍÔÛÙÒÛÂȘ. O ·‰Úfi˜ ‚ÈÔ¯ËÌÈÎfi˜ Î·È Ô ÂÓ‰Âϯ‹˜¤ÏÂÁ¯Ô˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙÔ˘ ÌÂÙ·‚Ô-ÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘, ηıÒ˜ Î·È Ô ¤ÏÂÁ¯Ô˜ ÁÈ·Û˘ÛÙËÌ·ÙÈÎfi ÓfiÛËÌ·, ‹Ù·Ó ·ÚÓËÙÈÎÔ›. ™Â ËÏÈΛ·ÂÓfi˜ ¤ÙÔ˘˜, Ë ·ÛıÂÓ‹˜ ›¯Â ¿ÏÈ ÂÏÂÁ¯ı› Û ¡Ô-ÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ, fiÔ˘ Î·È ÙfiÙ ·ÔÎÏ›ÛÙËΠÓÂ-ÊÚÈ΋, ηډÈÔÏÔÁÈ΋ ‹ ¿ÏÏË Û˘ÛÙËÌ·ÙÈ΋ ¿ıËÛË.

∏ ÎÏÈÓÈ΋ Î·È ·ÂÈÎÔÓÈÛÙÈ΋ ÂÈÎfiÓ· Ù˘ ·ÛıÂ-ÓÔ‡˜ ¤ıÂÛ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Nail-Patella. °ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ‰ÂÓ ¤ÁÈÓ ÏfiÁˆ ¿ÚÓËÛË˜ÙˆÓ ÁÔÓ¤ˆÓ.

∞ÊÔ‡ Ù¤ıËΠÚÔÂÁ¯ÂÈÚËÙÈο ‰˘Ó·ÌÈÎfi˜ Ó¿ÚıË-η˜ ¤ÎÙ·Û˘ Ù‡Ô˘ Orthotec ÁÈ· 2 ÂÚ›Ô˘ Ì‹Ó˜(∂ÈÎfiÓ· 5), ¯ÂÈÚÔ˘ÚÁ‹ıËΠÛÙËÓ ÚfiÛıÈ· ÂÈÊ¿ÓÂÈ·ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ·ÁÎÒÓ· Ì ÙÔÌ‹ Ù‡Ô˘ “Z” Î·È ¤ÁÈÓÂÂÈÌ‹Î˘ÓÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÙˆÓ ÙÂÓfiÓÙˆÓ ÙˆÓηÌÙ‹ÚˆÓ ÙÔ˘ ·ÁÎÒÓ·. ªÂÙÂÁ¯ÂÈÚËÙÈο, ÙÔÔıÂ-Ù‹ıËΠÂÎ Ó¤Ô˘ Ô ›‰ÈÔ˜ ‰˘Ó·ÌÈÎfi˜ Ó¿ÚıËη˜ ÁÈ· 6Ì‹Ó˜ Î·È ¤ÁÈÓ ÚÔԉ¢ÙÈ΋ ¤ÎÙ·ÛË ÙÔ˘ ·ÁÎÒÓ·ÛÙȘ 165-170 ÌÔ›Ú˜ (∂ÈÎfiÓ· 6). ªÂÙ¿ ÙËÓ ·Ê·›ÚÂ-ÛË ÙÔ˘ Ó¿ÚıËη, Ë ¤ÎÙ·ÛË ÂÚÈÔÚ›ÛÙËΠηٿ 15-

∂ÈÎfiÓ· 1. OÓ˘¯Ô‰˘ÛÏ·Û›·. ∂ÈÎfiÓ· 2. ™˘ÁÁÂÓ‹˜ Û‡ÁÎ·Ì„Ë ·ÁÎÒÓ·.

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20 ÌÔ›Ú˜. ∏ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ·ÛıÂÓÔ‡˜ Û˘ÓÂ-¯›ÛÙËΠÁÈ· ÌÂÚÈÎÔ‡˜ Ì‹Ó˜ ·ÎfiÌ· Î·È ÂȂ‚·ÈÒ-ıËÎÂ Ë ÛÙ·ıÂÚÔÔ›ËÛË Ù˘ ¤ÎÙ·Û˘.

™˘˙‹ÙËÛË ∆o NPS Â›Ó·È Û¿ÓÈÔ ÁÂÓÂÙÈÎfi ÓfiÛËÌ· Ô˘ ÂΉË-

ÏÒÓÂÙ·È ¿ÓÙ· Ì ·ÓˆÌ·Ï›Â˜ ·fi ÙÔ ÛÎÂÏÂÙÈÎfi Û‡-ÛÙËÌ· Î·È ÂÓ›ÔÙÂ Û˘Ó‰˘¿˙ÂÙ·È Ì ÓÂÊÚÈ΋ ÓfiÛÔ,ÔÊı·ÏÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Î·È Û‡Ó‰ÚÔÌÔ Good-pasture.

OÈ ÛÎÂÏÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÂΉËÏÒÓÔÓÙ·È Î˘Ú›ˆ˜ÛÙȘ ÂÈÁÔÓ·Ù›‰Â˜ (·Ô˘Û›· ‹ ˘ÔÏ·Û›·, knock-knee), ÛÙÔ˘˜ ·ÁÎÒÓ˜ (·Ï·Û›· ‹ ˘ÔÏ·Û›·, Û‡-Áη„Ë) Î·È ÛÙ· Ï·ÁfiÓÈ· ÔÛÙ¿ (ÂÍÔÛÙÒÛÂȘ). ¶·Ú·-ÙËÚ›ٷÈ, ›Û˘, ÔÓ˘¯Ô‰˘ÛÏ·Û›· (·Ô˘Û›·, ·Ô-¯ÚˆÌ·ÙÈÛÌfi˜, ÎÔÈÏÔÓ˘¯›·). OÈ ‚Ï¿‚˜ Â›Ó·È Û˘Ó‹-ıˆ˜ Û˘ÌÌÂÙÚÈΤ˜. ™˘¯Ó¿ Û˘Ó˘¿Ú¯Ô˘Ó ·˘¯ÂÓÈ΋ÏÂ˘Ú¿, ˘ÔÏ·Û›· ¤Íˆ ÌËÚÈ·›ˆÓ ÎÔÓ‰‡ÏˆÓ ‹ ÎÔÓ-‰‡ÏˆÓ ‚Ú·¯ÈÔÓ›Ô˘ (Capitelum) ‹ ÎÂÊ·Ï‹˜ ÎÂÚΛ‰Ô˜,ÎÂÊ·Ï‹˜ ÂÚfiÓ˘, ·Ï·Û›Â˜ Ì˘ÒÓ (΢ڛˆ˜ ÙÔ˘ Ì›-˙ÔÓÔ˜ ıˆÚ·ÎÈÎÔ‡) Î·È Û˘ÁÁÂÓ‹˜ ·Ô˘Û›· ÔÓ˘¯ÔÊfi-

ÚˆÓ Ê·Ï¿ÁÁˆÓ (13). ∏ ·Ô˘Û›· ÙˆÓ ÂÈÁÔÓ·Ù›‰ˆÓ‰ÂÓ ÂËÚ¿˙ÂÈ ÙË ÏÂÈÙÔ˘ÚÁÈ΋ ÈηÓfiÙËÙ· ÙÔ˘ ·Ùfi-ÌÔ˘, ‰ÂÓ ÂÈÙÚ¤ÂÈ, fï˜, ÙËÓ ¤ÓÙÔÓË ¿ÛÎËÛË Î·Èȉȷ›ÙÂÚ· ÙÔÓ ÚˆÙ·ıÏËÙÈÛÌfi. ŸÌˆ˜, Û˘¯Ó¿ ÂÈ-ϤÎÂÙ·È Ì ÔÛÙÂÔ·ÚıÚ›Ùȉ·, Ë ÔÔ›· ÌÔÚ› Ó· ›-Ó·È ‹È· Î·È Ó· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Û˘ÓÙËÚËÙÈο, ÌÔ-Ú› fï˜ Û¿ÓÈ· Ó· ¯ÚÂÈ·ÛÙ› ·ÚıÚÔÏ·ÛÙÈ΋ ·Ô-ηٿÛÙ·ÛË (14). ∏ ·ÚÔ˘Û›· ÙˆÓ ˘fiÏÔÈˆÓ ÛÎÂ-ÏÂÙÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ‰ËÌÈÔ˘ÚÁ› ÂÚÈÔÚÈÛÌfi Ù˘ ÎÈ-ÓËÙÈÎfiÙËÙ·˜ ηÈ, ÌÂÚÈΤ˜ ÊÔÚ¤˜, ÛÔ‚·Úfi ·ÈÛıËÙÈÎfiÚfi‚ÏËÌ·. ∏ ·ÛıÂÓ‹˜ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È ·ÚÔ˘-Û›·˙Â, ÂÎÙfi˜ ·fi ÙËÓ ÔÓ˘¯Ô‰˘ÛÏ·Û›· (ÁÈ· ÙËÓÔÔ›· Î·È ÚÔÛ‹Ïı ÛÙÔ ÓÔÛÔÎÔÌ›Ô), ÙȘ ÂÍ‹˜ ÛÎÂ-ÏÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜: Û‡Áη„Ë ·ÁÎÒÓˆÓ, ·Ô˘Û›·ÂÈÁÔÓ·Ù›‰ˆÓ Î·È Ï·ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ.

™ÙÔ 25% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Û˘Ó˘¿Ú¯ÂÈ ÓÂÊÚÔ-¿ıÂÈ· ¿ÏÏÔÙ ¿ÏÏ˘ ‚·Ú‡ÙËÙ·˜ Î·È ÔÛÔÛÙfi 10%ÊÙ¿ÓÂÈ Û ÙÂÏÈÎfi ÛÙ¿‰ÈÔ ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜(15). ∏ ÓÂÊÚÈ΋ Û˘ÌÌÂÙÔ¯‹ ‰È·ÎÚ›ÓÂÙ·È Û Ì›˙ÔÓ·Î·È ÂÏ¿ÛÛÔÓ·. ªÂ›˙ˆÓ ¯·Ú·ÎÙËÚ›˙ÂÙ·È Ë ÌÈÎÚÔÛÎÔ-È΋ ·ÈÌ·ÙÔ˘Ú›·, Ë ÚˆÙÂ˚ÓÔ˘Ú›·, ÙÔ Û‡Ó‰ÚÔÌÔ

∂ÈÎfiÓ· 3. ÀÔÏ·ÛÙÈΤ˜ ÎÂʷϤ˜ ÎÂÚΛ‰ˆÓ. ∂ÈÎfiÓ· 4. ∞Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ.

∂ÈÎfiÓ· 5. ∂Ê·ÚÌÔÁ‹ ‰˘Ó·ÌÈÎÔ‡ Ó¿ÚıËη. ∂ÈÎfiÓ· 6. ∂ÈÌ‹Î˘ÓÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÙÔ˘ ·ÁÎÒÓ· (ÙÔÌ‹Ù‡Ô˘ ∑).

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Alport, Ë ÛÂÈÚ·Ì·ÙÔÓÂÊÚ›Ùȉ·, ÙÔ ÓÂÊÚˆÛÈÎfi Û‡Ó-‰ÚÔÌÔ, ÙÔ Ô›‰ËÌ·, Ë ˘¤ÚÙ·ÛË Î·È Ë ÓÂÊÚÈ΋ ·ÓÂ-¿ÚÎÂÈ· Î·È ÂÏ¿ÛÛˆÓ Ë ÓÂÊÚÔÏÈı›·ÛË, ÔÈ Û˘ÁÁÂÓ›˜‰È·Ì·Úٛ˜ Ô˘ÚËÙ‹ÚˆÓ Î·È ÔÈ ‰È·Ì·Úٛ˜ ·ÛÙˆ˜.

¶ÈÔ Û¿ÓÈ·, Û˘Ó‰˘¿˙ÂÙ·È Ì ÔÊı·ÏÌÈΤ˜ ·Óˆ-̷ϛ˜ (ÌÈÎÚÔʷΛ·, ηٷÚÚ¿ÎÙË, ÎÂÚ·ÙfiΈÓÔ,ÁÏ·‡ÎˆÌ·), ÔÏ˘·ÚÙËÚ›Ùȉ·, ÓÔÛ‹Ì·Ù· ÙÔ˘ Û˘Ó-‰ÂÙÈÎÔ‡ ÈÛÙÔ‡ (Û. Goodpasture) Î·È Û¯ÈÛٛ˜ (6-8,16). ¶ÚfiÛÊ·Ù·, ‰ËÌÔÛȇÙËΠÂÚ›ÙˆÛË Á˘Ó·›-η˜ Ì NPS Î·È ªELAS, ‰Â›¯ÓÔÓÙ·˜ Èı·Ó‹ Û˘Û¯¤-ÙÈÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ì ·ÓˆÌ·Ï›Â˜ Ù˘ ·Ó·Ó¢-ÛÙÈ΋˜ ·Ï‡ÛÔ˘ (17).

∏ ÓÂÊÚÈ΋ Û˘ÌÌÂÙÔ¯‹ Ê·›ÓÂÙ·È Ó· ηıÔÚ›˙ÂÙ·ÈÁÂÓÂÙÈο ·fi Ì›· Ó¤· ÌÂÙ¿ÏÏ·ÍË, Ë ÔÔ›· ÚfiÛÊ·-Ù· Èı·ÓÔÏÔÁÂ›Ù·È ˆ˜ ˘Â‡ı˘ÓË (12). ∆Ô ÁÔÓ›‰ÈÔLMX1B Ú˘ıÌ›˙ÂÈ ¿ÌÂÛ· ÙËÓ ·ÚÔ˘Û›· ÙˆÓ ‚·ÛÈÎÒÓÚˆÙÂ˚ÓÒÓ (·3 Î·È ·4) ÙÔ˘ ÎÔÏÏ·ÁfiÓÔ˘ πV, Ô˘·ÔÙÂÏ› ÙÔ Î‡ÚÈÔ ‰ÔÌÈÎfi Û˘ÛÙ·ÙÈÎfi Ù˘ ‚·ÛÈ΋˜ÌÂÌ‚Ú¿Ó˘ ÙÔ˘ ÛÂÈÚ¿Ì·ÙÔ˜ (µª™). ∏ ÌÂÙ¿ÏÏ·ÍË·˘ÙÔ‡ Ê·›ÓÂÙ·È fiÙÈ ·ÔÚÚ˘ıÌ›˙ÂÈ ÙËÓ ÈÛÔÚÚÔ›·ÙˆÓ ·3 Î·È ·4 ÚˆÙÂ˚ÓÒÓ Ù˘ µª™, Ì ·ÔÙ¤ÏÂÛÌ·ÙË ÓÂÊÚÔ·ıÔÏÔÁÈ΋ ÂÈÎfiÓ· ÙÔ˘ NPS. ∞ÛıÂÓ›˜ ÌÂNPS Î·È ÓÂÊÚˆÛÈÎfi Û‡Ó‰ÚÔÌÔ ‹ ¿ÏÏË Û˘Ó‰˘·Ṳ̂-ÓË ÓÂÊÚÈ΋ ÓfiÛÔ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi Ù˘ÈΤ˜ ‰Ô-ÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙË µª™, Ì ÌÂȈ̤ÓË ·ÚÔ˘Û›··3 Î·È ·4 ÚˆÙÂ˚ÓÒÓ (18,19).

∏ ‰È¿ÁÓˆÛË ÂȂ‚·ÈÒÓÂÙ·È ·ÂÈÎÔÓÈÛÙÈο ηÈÁÂÓÂÙÈο. ∏ ·ÚÔ˘Û›· ÔÓ˘¯Ô‰˘ÛÏ·Û›·˜ Î·È ÙÂÚ˘-Á›ˆÓ Ì ۇÁη„Ë ÛÙÔ˘˜ ·ÁÎÒÓ˜, ηıÒ˜ Î·È Ô ·ÎÙÈ-ÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÛÙËÓ ·ÛıÂÓ‹ Ì·˜, ÛÙÔÓ ÔԛԉȷÈÛÙÒıËΠ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ Î·È Ï·ÁfiÓȘÂÍÔÛÙÒÛÂȘ, ¤ıÂÛ·Ó ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘.∏ ·ÚÔ˘Û›· ÙˆÓ Ï·ÁÔÓ›ˆÓ ÂÍÔÛÙÒÛÂˆÓ Â›Ó·È ·ıÔ-ÁÓˆÌÔÓÈÎfi ‡ÚËÌ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘. À¿Ú¯ÂÈ ÛÙÔ80% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Î·È ··ÓÙ¿Ù·È ÌfiÓÔ ÛÙÔ¡PS (20). (¢˘ÛÙ˘¯Ò˜, ÔÈ ·ÎÙÈÓÔÁڷʛ˜ ·fi ÙȘ Ï·-ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ ·ÚÂÏ‹ÊıËÛ·Ó ·fi ÙÔ˘˜ ÁÔÓ›˜ÚÈÓ ˘¿ÚÍÂÈ ‰˘Ó·ÙfiÙËÙ· ʈÙÔÁÚ¿ÊÈÛ‹˜ ÙÔ˘˜.∂ÈϤÔÓ, ÔÈ ÁÔÓ›˜ ‰ÂÓ ÚÔ¯ÒÚËÛ·Ó Û ÁÂÓÂÙÈÎfi¤ÏÂÁ¯Ô).

O ¤ÏÂÁ¯Ô˜ Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ‚·ÛÈÎÒÓ ÔÚÁ¿ÓˆÓ,fiˆ˜ ÓÂÊÚÒÓ Î·È ÔÊı·ÏÌÒÓ, ηıÒ˜ ›Û˘ Ô ¤ÏÂÁ-¯Ô˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ Î·È ÓÔÛËÌ¿-ÙˆÓ Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡, Â›Ó·È ··Ú·›ÙËÙ·. ™ÙËÓ·ÛıÂÓ‹ Ì·˜ ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó Û˘Ó˘¿Ú¯Ô˘Û˜‰È·Ù·Ú·¯¤˜.

¢È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ı· Ú¤ÂÈÓ· Á›ÓÂÈ ·fi ¿ÏÏ· ÓÔÛ‹Ì·Ù· ‹ ηٷÛÙ¿ÛÂȘ Ô˘ ·-ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ì ۇÁÎ·Ì„Ë ·ÁÎÒÓ·, fiˆ˜ ÙÔ Û‡Ó-‰ÚÔÌÔ “Escobar” (Multiple Pterygium Syndrome)fiÔ˘ ·Ó¢ڛÛÎÔÓÙ·È ÙÂÚ‡ÁÈ· Î·È ‰˘ÛϷۛ˜ ÂÈÁÔ-Ó·Ù›‰ˆÓ Î·È Û˘¯Ó¿ Û˘Ó˘¿Ú¯Ô˘Ó ÌÈÎÚÔÁÓ·ı›·, ·ÙÂ-Ϥ˜ Ï˘ÎfiÛÙÔÌ·, ÙÂÚ‡ÁÈÔ ÙÚ·¯‹ÏÔ˘, ηÌÙÔ‰·ÎÙ˘-

Ï›· ‹ Û˘Ó‰·ÎÙ˘Ï›·, ÎÚ˘„ÔÚ¯›·, ÛÎÔÏ›ˆÛË, ·ʈÛËÎ·È Ó·ÓÈÛÌfi˜ Î·È ÙÔ Û‡Ó‰ÚÔÌÔ ÎÓËÌÈ·›ˆÓ ÙÂÚ˘Á›ˆÓ,ÙÔ ÔÔ›Ô Û˘Ó‰˘¿˙ÂÈ ÎÓËÌÈ·›Â˜ Ù˘¯¤˜, Û˘Ó‰·ÎÙ˘Ï›·,Û¯ÈÛٛ˜, ÎÚ˘„ÔÚ¯›·, ‰˘ÛÏ·Û›· ÔÛ¯¤Ô˘ (13).

∞ÛıÂÓ›˜ Ì NPS Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Û˘ÁÁÂÓ‹Û‡ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ, ¯ˆÚ›˜ ÓÂÊÚÈ΋ ‹ ¿ÏÏË Û˘ÛÙË-Ì·ÙÈ΋ ÓfiÛÔ (ÎÔÏÏ·ÁfiÓˆÛË, ·ÁÁÂÈ›Ùȉ·, ÔÊı·ÏÌÈ΋¿ıËÛË), ‰‡Ó·ÓÙ·È Ó· ·ÔÎÙ‹ÛÔ˘Ó ÌÂÙ¿ ·fi ¯ÂÈ-ÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË, ‚ÂÏÙ›ˆÛË Ù˘ ÁˆÓ›·˜Î¿Ì„˘ ÙÔ˘ ·ÁÎÒÓ· Î·È Ó· ‰È¿ÁÔ˘Ó Û¯Â‰fiÓ Ê˘ÛÈÔ-ÏÔÁÈÎfi ‚›Ô, ·ÚÎÒ˜ ·˘ÙÔÂ͢ËÚÂÙÔ‡ÌÂÓÔÈ. ∏ ¯Ú‹-ÛË Û˘Ó‰˘·Ṳ̂Ó˘ ıÂڷ›·˜ ‰˘Ó·ÌÈÎÒÓ Ó·Úı‹ÎˆÓÚÔÂÁ¯ÂÈÚËÙÈο ηÈ, ·ÎÔÏÔ‡ıˆ˜, Ë ¯ÂÈÚÔ˘ÚÁÈ΋·ÔηٿÛÙ·ÛË Ù˘ Û‡Áη̄˘ ÙˆÓ ·ÁÎÒÓˆÓ(fiˆ˜ ¤ÁÈÓ Ì ÙËÓ ·ÛıÂÓ‹ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È) ÂÈ-Ù˘Á¯¿ÓÂÈ ÌÂÁ·Ï‡ÙÂÚË ¤ÎÙ˘ÍË (ÂÚ›Ô˘ 155-160ÌÔ›Ú˜). ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÊ·ÚÌÔÁ‹ ‰˘Ó·ÌÈÎÔ‡Ó¿ÚıËη ÁÈ· ‰È¿ÛÙËÌ· ÌÂÁ·Ï‡ÙÂÚÔ ‹ ›ÛÔ ÙÔ˘ ÂÍ·-Ì‹ÓÔ˘, Ì ÙÔÓ ÔÔ›Ô ı· Á›ÓÂÙ·È Û˘Ó¯‹˜ ¿ÛÎËÛˉȷٷÙÈÎÒÓ ‰˘Ó¿ÌÂˆÓ ÛÙ· ı˘Ï·ÎÔÛ˘Ó‰ÂÛÌÈο ÛÙÔÈ-¯Â›· (‰˘Ó¿ÌÂȘ ÂÚ˘ÛÌÔ‡), ÛÙ·ıÂÚÔÔÈ› ÙÔ ¯ÂÈ-ÚÔ˘ÚÁÈÎfi ·ÔÙ¤ÏÂÛÌ· ¤ÛÙˆ Î·È ·Ó Ë ÂÊ·ÚÌÔÁ‹ Á›-ÓÂÙ·È ÌÂÚÈÎÒ˜ ‹ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ó‡ÎÙ·˜. ∆Ô·ÙÂϤ˜, fï˜, ·ÈÛıËÙÈÎfi Î·È ÏÂÈÙÔ˘ÚÁÈÎfi ·ÔÙ¤ÏÂ-ÛÌ· ÚÔ‚ÏËÌ·Ù›˙ÂÈ ÔÏÏÔ‡˜ ·ÛıÂÓ›˜, ¯ˆÚ›˜ fï˜Ì¤¯ÚÈ Û‹ÌÂÚ· Ó· ˘¿Ú¯ÂÈ ‰˘Ó·ÙfiÙËÙ· Ï‹ÚÔ˘˜·ÔηٿÛÙ·Û˘.

∞ÛıÂÓ›˜ Ì NPS ÙÂÎÓÔÔÈÔ‡Ó ·È‰È¿ Ì ÙÔ Û‡Ó-‰ÚÔÌÔ (·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡Ó ÁÔÓ›‰ÈÔ). O ΛÓ-‰˘ÓÔ˜ ·Ó¿Ù˘Í˘ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ Â›Ó·È 25% Î·È ÓÂ-ÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ 10% (15).

∏ ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ì ÚÔÁÂÓÓËÙÈÎfi¤ÏÂÁ¯Ô Â›Ó·È Û‹ÌÂÚ· ÂÊÈÎÙ‹ Ì ˘ÂÚ‹¯Ô˘˜ Î·È ÌÂÌÔÚȷ΋ ·Ó¿Ï˘ÛË DNA (21). °ÂÓÈο, Ë ÙÂÎÓÔÔ›ËÛËÛ ÔÈÎÔÁ¤ÓÂȘ Ì NPS ·Ôı·ÚÚ‡ÓÂÙ·È ·ÊÂÓfi˜ ÁÈ·ÙÔÓ Î›Ó‰˘ÓÔ Û˘Ó‡·Ú͢ ÓÂÊÚÈÎÒÓ ‚Ï·‚ÒÓ, ·ÊÂ-Ù¤ÚÔ˘ ÁÈ· Ó· ÂÚÈÔÚÈÛÙ› Ô ·ÚÈıÌfi˜ ÊÔÚ¤ˆÓ ÓÔÛË-ÚÒÓ ÁÔÓȉ›ˆÓ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ (15). ∂›Ó·È, fï˜,ÁÂÁÔÓfi˜ fiÙÈ Û‹ÌÂÚ· ÌÔÚ› Ó· Ú·ÁÌ·ÙÔÔÈËı›ÚÔÁÂÓÓËÙÈ΋ ‚ÈÔ„›· ÓÂÊÚÔ‡ (22), ÒÛÙ ¤ÁηÈÚ·Ó· ‰È·ÈÛÙÒÓÂÙ·È Ë Û˘Ó‡·ÚÍË ‹ ÌË ÓÂÊÚÈ΋˜ Ófi-ÛÔ˘ ÛÙÔ ¤Ì‚Ú˘Ô, ¯ˆÚ›˜ fï˜ ¿ÓÙ· Ó· Â›Ó·È ‰˘Ó·-Ùfi˜ Ô Î·ıÔÚÈÛÌfi˜ Ù˘ Û Ì›˙ÔÓ· ‹ ÂÏ¿ÛÛÔÓ· ÓÂ-ÊÚÈ΋ ‚Ï¿‚Ë.

µÈ‚ÏÈÔÁÚ·Ê›·1. Aschner B. A typical hereditary syndrome: dystrophy of the

nails, congenital defect of the patella and congenital defectof the head of radius. JAM∞ 1934;102:2017-2020.

2. Turner JW. A hereditary arthrodysplasia associated withhereditary dystrophy of the nails. JAMA 1993;100:882-884.

3. Cottereill CP, Jacobs P. Hereditary arthro-osteo-onychodysplasia associated with iliac horns. Br J Clin Pract1961;15:933-941.

MARC-APR 03 14-05-03 14:48 ™ÂÏ›‰·143

4. Leahy MS. The hereditary nephropathy of osteo-onychodysplasia. Nail-patella syndrome. Am J Dis Child1966;112:237-241.

5. Taguchi T, Takebayashi S, Nishimura M, Tsuru N.Nephropathy of nail-patella syndrome. Ultrastruct Pathol1988;12:175-183.

6. Mark TM, Rywlin AM, Unger H. Cystic adventitialdegeneration of the popliteal artery. Its occurrence in apatient with the nail-patella syndrome. Arch Pathol Lab Med1983;107:186-188.

7. Lichter PR, Richards JE, Downs CA, Stringham HM,Boehnke M, Farley FA. Cosegregation of open-angleglaucoma and the nail-patella syndrome. Am J Ophthalmol1997;124:506-515.

8. Curtis JJ, Bhathena D, Leach RP, Galla JH, Lucas BA, LukeRG. Goodpasture’s syndrome in a patient with the nail-patella syndrome. Am J Med 1976;61:401-404.

9. Little EM. Congenital absence or delayed development ofthe patella. Lancet 1897;2:781.

10. McIntosh I, Clough MV, Schaffer AA, Puffenberger EG,Horton VK, Peters K et al. Fine mapping of the nail-patellasyndrome locus at 9q34. Am J Hum Genet 1997;60:133-142.

11. McIntosh I, Dreyer SD, Clough MV, Dunston JA, Eyaid W,Roig CM et al. Mutation analysis of LMX1B gene in nail-patella syndrome patients. Am J Hum Genet 1998;63:1651-1658.

12. Chen H, Lun Y, Ovchinnikov D, Kokubo H, Oberg KC,Pepicelli CV et al. Limb and kidney defects in Lmx1b mutantmice suggest an involvement of LMX1B in human nailpatella syndrome. Nat Genet 1998;19:51-55.

13. Jonesk ISH. Recognizable patterns of human congenitalmalformations. 5 th ed. Philadelphia: Ed Saunders; 1997. p.438-439.

14. Lachiewicz PF, Herndon CD. Total knee arthroplasty forosteoarthritis in hereditary onycho-osteodysplasia (nail-patellasyndrome): a case report. Am J Orthop 1997;26:129-130.

15. Looij BJ Jr, te Slaa RL, Hogewind BL, van de Kamp JJ.Genetic counselling in hereditary osteo-onychodysplasia(HOOD, nail-patella syndrome) with nephropathy. J MedGenet 1988;25:682-686.

16. Richieri-Costa A. Antecubital pterygium and cleft lip/palatepresenting as signs of the nail-patella syndrome: report of aBrazilian family. Am J Med Genet 1991;38:9-12.

17. Finsterer J, Stollberger C, Wanschitz J, Jaksch M, Budka H.Nail-patella syndrome associated with respiratory chaindisorder. Eur Neurol 2001;46:92-95.

18. Morello R, Zhou G, Dreyer SD, Harvey SJ, Ninomiya Y,Thorner PS et al. Regulation of glomerular basementmembrane collagen expression by LMX1B contributes torenal disease in nail patella syndrome. Nat Genet2001;27:205-208.

19. Rohr C, Prestel J, Heidet L, Hosser H, Kriz W, Johnson RL etal. The LIM-homeodomain transcription factor Lmx1b playsa crucial role in podocytes. J Clin Invest 2002;109:1073-1082.

20. Goshen E, Schwartz A, Zilka LR, Zwas ST. Bilateralaccessory iliac horns: pathognomonic findings in Nail-patella syndrome. Scintigraphic evidence on bone scan.Clin Nucl Med 2000;25:476-477.

21. Pinette MG, Ukleja M, Blackstone J. Early prenatal diagnosisof nail-patella syndrome by ultrasonography. J UltrasoundMed 1999;18:387-389.

22. Gubler MC, Levy M. Prenatal diagnosis of nail-patellasyndrome by kidney biopsy. Am J Med Genet1993;43:693-696.

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‰ËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ÂÓÙÂÚÈ΋˜ ·fiÊڷ͢. ∞ÓÙÈÌÂ-Ùˆ›˙ÂÙ·È Ì ÂÚ¢ÓËÙÈ΋ Ï··ÚÔÙÔÌ›·, Â¿Ó ‰ÂÓ˘¿Ú¯ÂÈ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ‰È¿ÁÓˆÛË. ∂Áηı›ÛٷٷÈÎÔÏÔÛÙÔÌ›· ÎÂÓÙÚÈο Ù˘ ·Á·ÁÁÏȷ΋˜ ‹ ˘ÔÁ·Á-ÁÏȷ΋˜ ˙ÒÓ˘ Î·È ·ÎÔÏÔ˘ı› Ë ÎÔÈÏÈÔÂÚÈÓÂ˚΋ ÂÁ-¯Â›ÚËÛË ·ÔηٿÛÙ·Û˘ ÙÔ˘ ÌÂÁ¿ÎÔÏÔ˘ Û ‰Â‡ÙÂ-

ÚÔ ÂÁ¯ÂÈÚËÙÈÎfi ¯ÚfiÓÔ (1). OÈ Georgeson Î·È Û˘Ó, ÙÔ1995, ÂÚȤÁÚ·„·Ó ÙËÓ Ù¯ÓÈ΋ Ï··ÚÔÛÎÔÈ΋˜ÂÁ¯Â›ÚËÛ˘ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ (2). ª¤¯ÚÈÛ‹ÌÂÚ·, ÂÏ¿¯ÈÛÙ˜ Â›Ó·È ÔÈ ·Ó·ÊÔÚ¤˜ ÛÙË Ï··ÚÔ-ÛÎÔÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÚÒÙË ÂÚ›-ÙˆÛË ÛÙËÓ ÂÏÏËÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›·, Ï··ÚÔÛÎÔÈ-΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ ÓÂÔÁÓÔ‡ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ.

�¶ÂÚ›ÏË„Ë: ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ÛÙË ÓÂÔÁÓÈ΋ËÏÈΛ· Û˘Ó‹ıˆ˜ ÂΉËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ·fiÊÚ·-͢ ÙÔ˘ ÂÓÙ¤ÚÔ˘ Ô˘ ÌÔÚ› Ó· ÂÈϯı› ÌÂÂÓÙÂÚÔÎÔÏ›Ùȉ·, Ë ÔÔ›· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Ì Â›-ÁÔ˘Û· ÎÔÏÔÛÙÔÌ›·. ∏ ·ÔηٿÛÙ·ÛË Ù˘ Û˘ÁÁÂ-ÓÔ‡˜ ·ÓˆÌ·Ï›·˜ Á›ÓÂÙ·È Û ‰Â‡ÙÂÚÔ ¯ÂÈÚÔ˘ÚÁÈÎfi¯ÚfiÓÔ. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÚÒÙË ÂÚ›ÙˆÛË ÛÙËÓ ÂÏ-ÏËÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›· ÓÂÔÁÓÔ‡ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿-ÎÔÏÔ, ÙÔ ÔÔ›Ô ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο Û¤ӷ ¯ÂÈÚÔ˘ÚÁÈÎfi ¯ÚfiÓÔ ¯ˆÚ›˜ ÎÔÏÔÛÙÔÌ›·. ∆Ô ÓÂÔ-ÁÓfi ·ÚÔ˘Û›·Û ÛËÌ›· ÂÓÙÂÚÈ΋˜ ·fiÊڷ͢,fiˆ˜ ›ۯÂÛË ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ Î·È ÌÂÙˆÚÈ-ÛÌfi ÎÔÈÏ›·˜. ¶ÚÔÂÁ¯ÂÈÚËÙÈο ¯ÔÚËÁ‹ıËΠÔÏÈ΋·ÚÂÓÙÂÚÈ΋ ‰È·ÙÚÔÊ‹, ·ÓÙÈ‚›ˆÛË Î·È ¤ÁÈÓ ÚÔÂ-ÙÔÈÌ·Û›· ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘. ™ÙÔ ¯ÂÈÚÔ˘ÚÁ›ԤÁÈÓ Ϸ·ÚÔÛÎÔÈ΋ ··ÁÁ›ˆÛË ÙÔ˘ ·ıÔÏÔÁÈ-ÎÔ‡ ÂÓÙ¤ÚÔ˘, ·Ó¿‰ÚÔÌË ‰È·ÚˆÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂ-ÎÙÔÌ‹ ÙÔ˘ ÔÚıÔ‡, ‰ÈÂ΂ÔÏ‹ Î·È Â͈ÙÂڛ΢ÛË ÙÔ˘·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ ̤ۈ ÙÔ˘ ·Ô‚ÏÂÓÓÔÁÔÓÈṲ̂ÓÔ˘Ì˘˚ÎÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜ ÙÔ˘ ÔÚıÔ‡ Î·È ÙÂÏÈÎÔ-ÙÂÏÈ΋ÂÓÙÂÚÔÚˆÎÙÈ΋ ·Ó·ÛÙfïÛË. ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ÔÚ›· ÙÔ˘ ÓÂÔÁÓÔ‡ ‹Ù·Ó ÔÌ·Ï‹ Î·È Ë ÏÂÈÙÔ˘ÚÁ›·ÙÔ˘ ÂÓÙ¤ÚÔ˘ ·ÔηٷÛÙ¿ıËΠϋڈ˜.

§¤ÍÂȘ ÎÏÂȉȿ: Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, ÓÂÔÁÓfi, Ï··-ÚÔÛÎÔÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋.

�Abstract: Congenital megacolon in newborninfants presents clinically as bowel obstruction. Incases complicated by enterocolitis, emergencycolostomy is established, followed later by thedefinitive, second stage, operation. This is the firstreport in the Greek literature of congenitalmegacolon in a neonate submitted to laparoscopicoperation without preceding colostomy. Theneonate presented with intestinal obstruction. Totalparenteral nutrition and intravenous antibioticswere given preoperatively and serial bowelwashouts were performed. The aganglionic colonwas removed laparoscopically and dissection of therectal mucosa was performed transanally. Theganglionic colon was pulled through the muscularcuff of the rectum and anastomosed above thedentate line, within the muscular cuff. Thepostoperative course was uncomplicated andbowel function after the operation was normal.

Key words: congenital megacolon, neonate,laparoscopic surgery.

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¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ¡ÂÔÁÓfi ¿ÚÚÂÓ ËÏÈΛ·˜ 15 ËÌÂÚÒÓ, Ì µ° 3210 g,

ÓÔÛËχıËΠÁÈ· Â̤ÙÔ˘˜ Î·È ‰È¿Ù·ÛË ÎÔÈÏ›·˜ ÏfiÁˆÂ›Û¯ÂÛ˘ ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ. ∞fi ÙÔÓ ÎÏÈÓÈÎfiÎ·È ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ÂÙ¤ıË Ë ‰È¿ÁÓˆÛË ÙÔ˘Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ (∂ÈÎfiÓ· 1).

∏ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂÙÔÈÌ·Û›· ÂÚÈÂÏ¿Ì‚·Ó ‰È·ÎÔ-‹ Ù˘ Û›ÙÈÛ˘, ¯ÔÚ‹ÁËÛË ÔÏÈ΋˜ ·ÚÂÓÙÂÚÈ΋˜ ‰È·-ÙÚÔÊ‹˜ Î·È ÂÓ‰ÔÊϤ‚È·˜ ·ÓÙÈ‚›ˆÛ˘, ηıÒ˜ Î·È ÚÔ-ÂÙÔÈÌ·Û›· ÙÔ˘ ÂÓÙ¤ÚÔ˘, ÙÔ ÂÚȯfiÌÂÓÔ ÙÔ˘ ÔÔ›Ô˘ÂÎÎÂÓÒıËΠÌÂ Û˘¯Ó¤˜, ·ӷϷ̂·ÓfiÌÂÓ˜ ÙÔÔıÂ-Ù‹ÛÂȘ ۈϋӷ ·ÂÚ›ˆÓ Î·È Ï‡ÛÂȘ ÌÂ Ê˘ÛÈÔÏÔÁÈÎfiÔÚfi. ∏ ÂÁ¯Â›ÚËÛË ¤ÁÈÓ Ϸ·ÚÔÛÎÔÈο, ¯ˆÚ›˜ ÎÔÏÔ-ÛÙÔÌ›·. ∏ ¤ÎÙ·ÛË Ù˘ ·Á·ÁÁÏȷ΋˜ Î·È ˘ÔÁ·ÁÁÏÈ·-΋˜ ˙ÒÓ˘ ηıÔÚ›ÛÙËΠ̠ٷ¯Â›Â˜ ‚ÈÔ„›Â˜ ηٿ ÙËÏ··ÚÔÛÎÔÈ΋ Ê¿ÛË Ù˘ ÂÁ¯Â›ÚËÛ˘ Î·È ·ÊÔÚÔ‡ÛÂÛÙÔ ÔÚıfi Î·È ÙÔ Î¿Ùˆ ÙÚÈÙËÌfiÚÈÔ ÙÔ˘ ÛÈÁÌÔÂȉԇ˜. ∏··ÁÁ›ˆÛË ÙÔ˘ ·ıÔÏÔÁÈÎÔ‡ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ·¯¤Ô˜ÂÓÙ¤ÚÔ˘ Î·È Ë ÎÈÓËÙÔÔ›ËÛË ·˘ÙÔ‡ ¤ÁÈÓ Ϸ·ÚÔÛÎÔ-Èο. ÃÚËÛÈÌÔÔÈ‹ıËÎ·Ó 3 trocar, 1 ÁÈ· ÙËÓ Î¿ÌÂÚ·Î·È 2 ÁÈ· Ù· ÂÚÁ·Ï›· ÂÚÁ·Û›·˜. ∏ ›ÂÛË ÙÔ˘ CO2 ΢-Ì¿ÓıËΠ۠›‰· 3-5 mmHg. ∞ÎÔÏÔ‡ıËÛÂ Ô ÂÚÈ-ÓÂ˚Îfi˜ ¯ÚfiÓÔ˜, Ô ÔÔ›Ô˜ ÂÚÈÂÏ¿Ì‚·Ó ·Ó¿‰ÚÔÌˉȷڈÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂÎÙÔÌ‹ ÙÔ˘ ÔÚıÔ‡ (∂ÈÎfiÓ· 2),‰ÈÂ΂ÔÏ‹ Î·È Â͈ÙÂڛ΢ÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ ̤-Ûˆ ÙÔ˘ ·Ô‚ÏÂÓÓÔÁÔÓÈṲ̂ÓÔ˘ ÎÔÏÔ‚ÒÌ·ÙÔ˜ ÙÔ˘ ÔÚ-ıÔ‡ (∂ÈÎfiÓ· 3) Î·È ÙÂÏÈÎÔ-ÙÂÏÈ΋ ÎÔÏÔÚˆÎÙÈ΋ ·Ó·-ÛÙfïÛË. ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· ÙÔ˘ ÓÂÔÁÓÔ‡ ‹Ù·ÓÔÌ·Ï‹ Î·È Ë ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÂÓÙ¤ÚÔ˘ ÌÂÙ¿ ÙËÓ ÂÁ¯Â›-ÚËÛË Ê˘ÛÈÔÏÔÁÈ΋.

™˘˙‹ÙËÛË ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·,

Û˘Ó‹ıˆ˜ ÂΉËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ·fiÊڷ͢ ÙÔ˘·¯¤Ô˜ ÂÓÙ¤ÚÔ˘, Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Â̤ÙÔ˘˜,

ÌÂÙˆÚÈÛÌfi ÎÔÈÏ›·˜ Î·È Â›Û¯ÂÛË ·ÂÚ›ˆÓ Î·È ÎÔ-Ú¿ÓˆÓ. ∏ ÙÔÔı¤ÙËÛË ÛˆÏ‹Ó· ·ÂÚ›ˆÓ ÛÙÔ ÔÚıfiÂÍÔ˘‰ÂÙÂÚÒÓÂÈ ÙË Û‡Û·ÛË ÙÔ˘ ·Á·ÁÁÏÈ·ÎÔ‡ ̤-ÚÔ˘˜ Î·È ·ÎÔÏÔ˘ıÂ›Ù·È ·fi ÂÎÚËÎÙÈ΋ ·Ô‚ÔÏ‹ ·Â-Ú›ˆÓ Î·È ÎÔÚ¿ÓˆÓ, ÂÊfiÛÔÓ Ô ÛˆÏ‹Ó·˜ ¤¯ÂÈ Ì‹ÎÔ˜fiÛÔ Î·È ÙÔ - Û ۇ۷ÛË - ¤ÓÙÂÚÔ (3). ™˘¯Ó‹ ÂÈ-ÏÔ΋ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈ-Λ· Â›Ó·È Ë ÂÓÙÂÚÔÎÔÏ›ÙȘ, Ë ÔÔ›· ··ÈÙ› ›ÁÔ˘-Û· ÎÔÏÔÛÙÔÌ›·. ∏ ¤ÁηÈÚË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘ÁÁÂ-ÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘, Ë ÔÔ›· Á›ÓÂÙ·È Ì ÙËÓ ÎÏÈÓÈ΋ÂÎÙ›ÌËÛË, ÙË ‚ÈÔ„›· ÙÔ˘ ÔÚıÔ‡ Î·È ÙÔÓ ·ÂÈÎÔÓÈÛÙÈ-Îfi ¤ÏÂÁ¯Ô, Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÚfiÏË„Ë Ù˘ ÂÓÙÂÚÔÎÔ-Ï›Ùȉ·˜ Î·È ÛÙËÓ ·ÏÏ·Á‹ ÛÙÚ·ÙËÁÈ΋˜ ˆ˜ ÚÔ˜ Ù˯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ™ÙË Û˘ÁÎÂÎÚÈ̤ÓË ÂÚ›-ÙˆÛË, ¤ÁÈÓ ‰È·ÎÔ‹ Ù˘ Û›ÙÈÛ˘, ÙÔÔı¤ÙËÛË ÚÈÓÔ-Á·ÛÙÚÈÎÔ‡ ۈϋӷ, ¯ÔÚ‹ÁËÛË ÔÏÈ΋˜ ·ÚÂÓÙÂÚÈ΋˜‰È·ÙÚÔÊ‹˜ Î·È ÂÓ‰ÔÊϤ‚È·˜ ·ÓÙÈ‚›ˆÛ˘, ηıÒ˜ ηÈ

∂ÈÎfiÓ· 2. ∞Ó¿‰ÚÔÌË ‰È·ÚˆÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂÎÙÔÌ‹ ÙÔ˘ÔÚıÔ‡.

∂ÈÎfiÓ· 1. ¢È¿‚·ÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ Ì ‚¿ÚÈÔ. ∂ÈÎfiÓ·Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘.

∂ÈÎfiÓ· 3. ¢ÈÂ΂ÔÏ‹ Î·È Â͈ÙÂڛ΢ÛË ÙÔ˘ ·Á·ÁÁÏÈ·ÎÔ‡ ÙÌ‹Ì·-ÙÔ˜ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ ̤ۈ ÙÔ˘ ·Ô‚ÏÂÓÓÔÁÔÓÈṲ̂ÓÔ˘ Ì˘˚-ÎÔ‡ ¯ÈÙÒÓ· ÙÔ˘ ÔÚıÔ‡.

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Û˘¯Ó‹ ÙÔÔı¤ÙËÛË ÛˆÏ‹Ó· ·ÂÚ›ˆÓ ÛÙÔ ÔÚıfi ÁÈ··ÔÛ˘ÌÊfiÚËÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘.

ª¤¯ÚÈ Û‹ÌÂÚ·, ÁÈ· ÙËÓ ·ÔηٿÛÙ·ÛË ÙÔ˘ Û˘Á-ÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘, ¤¯Ô˘Ó ÂÊ·ÚÌÔÛÙ› ÂÈÙ˘¯Ò˜ ÌÂÏ··ÚÔÙÔÌ›· ‰È¿ÊÔÚ˜ Ù¯ÓÈΤ˜, ·fi ÙȘ Ôԛ˜ ÔÈÂÈÎÚ·Ù¤ÛÙÂÚ˜ Â›Ó·È ÔÈ Ù¯ÓÈΤ˜ Swenson,Duhamel Î·È Soave-Boley (4-7). ¶ÚfiÛÊ·Ù·, ÔÈGeorgeson Î·È Û˘Ó ‰ËÌÔÛ›Â˘Û·Ó ÙË Ï··ÚÔÛÎÔÈ-΋ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Î·È Û¿ÙÔÌ· ÓÂÔÁÓÈ΋˜ ËÏÈΛ·˜ (2,8). ™ÙËÓ ·ÚÔ‡Û· ÂÚ›-ÙˆÛË, ηٿ ÙË Ï··ÚÔÛÎÔÈ΋ ··ÁÁ›ˆÛË ÙÔ˘·ıÔÏÔÁÈÎÔ‡ ÂÓÙ¤ÚÔ˘, Ë ›ÂÛË ÙÔ˘ CO2 ‰È·ÙËÚ‹-ıËΠ۠¯·ÌËÏ¿ ›‰· 3-5 mmHg. ªÂÙ¿ ÙËÓÂÌÂÈÚ›· Ô˘ ·ÔÎÙ‹ıËΠÛÙȘ Ï··ÚÔÛÎÔÈΤ˜ ÂÁ-¯ÂÈÚ‹ÛÂȘ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÂÈÚ·Ì·-Ùfi˙ˆ·, ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο ·È‰› ËÏÈ-Λ·˜ 14 ÂÙÒÓ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, Ì ¿ÚÈÛÙÔ ÌÂ-ÙÂÁ¯ÂÈÚËÙÈÎfi ·ÔÙ¤ÏÂÛÌ· (9,10). ™ÙËÓ ÂÚ›ÙˆÛË·˘Ù‹, Ë ›ÂÛË ÙÔ˘ CO2 ÛÙËÓ ÂÚÈÙÔÓ·˚΋ ÎÔÈÏfiÙËÙ·‹Ù·Ó 10±2 mmHg. ∏ ÂÌÂÈÚ›· ·˘Ù‹ ·ÍÈÔÔÈ‹ıËÎÂηÈ, ¤ÙÛÈ, ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο ÓÂÔÁÓfiÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ¯ˆÚ›˜ ȉȷ›ÙÂÚË ‰˘ÛÎÔÏ›·.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Teitelbaum DH, Qualman SJ, Caniano DA. Hirschsprung’s

disease. Identification of risk factors for enterocolitis. AnnSurg 1988;207:240-244.

2. Georgeson KE, Fuenfer MM, Hardin WD. Primarylaparoscopic pull-through for Hirschsprung’s disease ininfants and children. J Pediatr Surg 1995;30:1017-1022.

3. ∫ÂÚ·Ì›‰·˜ ¢. ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ. π·ÙÚÈ΋ 1978;34:497-507.

4. Swenson O, Bill AH. Resection of the rectum andrectosigmoid with preservation of the sphincter for benignspastic lesions producing megacolon. Surgery1948;24:212-220.

5. Duhamel B. A new operation for the treatment ofHirschsprung’s disease. Arch Dis Child 1960;35:38-39.

6. Soave F. Hirschsprung’s disease: a new surgical technique.Arch Dis Child 1964;39:116-124.

7. Boley S. An endorectal pull-through operation with primaryanastomosis for Hirschsprung’s disease in infants andchildren. J Paediatr Surg 1995;30:1017-1022.

8. Georgeson KE, Cohen RD, Hebra A, Jona JZ, Powell DM,Rothenberg SS et al. Primary laparoscopic-assistedendorectal colon pull-through for Hirschsprung’s disease: anew gold standard. Ann Surg 1999;229:678-683.

9. ¶··Ó‰Ú¤Ô˘ ∂, ÃȈٛÓ˘ Ã, ª·ÏÙÔÁÈ¿ÓÓ˘ ¡, ∫Ô˘ÏfiÔ˘-ÏÔ˜ ∫, ÷ڛÛË µ, ¶··Ïfi˘ ∞ Î·È Û˘Ó. §··ÚÔÛÎÔÈ΋ÂÊ·ÚÌÔÁ‹ ÙˆÓ Ù¯ÓÈÎÒÓ Swenson, Duhamel Î·È SoaveÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÂÈÚ·Ì·ÙÈÎfiÌÔÓÙ¤ÏÔ. §··ÚÔÂÓ‰ÔÛÎÔÈ΋ ÃÂÈÚÔ˘ÚÁÈ΋ 2001;3:7-13.

10. ¶··Ó‰Ú¤Ô˘ ∂, ™˘Ú¿ÎÔ˜ ™, ÷ÚÌ¿Ó˘ °, ª·ÏÙÔÁÈ¿ÓÓ˘¡, ∑·¯·ÚfiÔ˘ÏÔ˜ ¢, ∫ÂÚ·Ì›‰·˜ ¢. §··ÚÔÛÎÔÈ΋ ¯ÂÈ-ÚÔ˘ÚÁÈ΋ ÛÙÔ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ: ¶ÂÚ›ÙˆÛË ·È‰ÈÔ‡ ËÏÈ-Λ·˜ 14 ÂÙÒÓ. ∂ÏÏËÓÈ΋ ÃÂÈÚÔ˘ÚÁÈ΋ (˘fi ¤Î‰ÔÛË).

HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 29-07-2002 HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 14-02-2003

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∂. ¶··Ó‰Ú¤Ô˘ ∆ÚÈfiψ˜ 1, ∆.∫. 151 27, ªÂÏ›ÛÛÈ·

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∂ÈÛ·ÁˆÁ‹∏ Û˘ÁÁÂÓ‹˜ ΢ÛÙÈ΋ ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›·

ÙÔ˘ Ó‡ÌÔÓ· (™∫∞¢¶) ·ÔÙÂÏ› Û¿ÓÈ· ‰˘ÛÏ·-Û›· ÙˆÓ Ó¢ÌfiÓˆÓ, ÌÂ Û˘¯ÓfiÙËÙ· Ô˘ ˘ÔÏÔÁ›˙Â-Ù·È Û 1 ÂÚ›ÙˆÛË ·Ó¿ 25000-35000 ΢‹ÛÂȘ (1).÷ڷÎÙËÚ›˙ÂÙ·È ·fi ÙË ‰ËÌÈÔ˘ÚÁ›· ·ÛÙÂˆÓ ÔÈΛ-ÏÔ˘ ÌÂÁ¤ıÔ˘˜, ÔÈ Ôԛ˜ ÂÓÙÔ›˙ÔÓÙ·È, ηٿ ÛÂÈÚ¿Û˘¯ÓfiÙËÙ·˜, ÛÙÔÓ ·ÚÈÛÙÂÚfi Ó‡ÌÔÓ· (45-51%),ÛÙÔÓ ‰ÂÍÈfi Ó‡ÌÔÓ· (29-35%) ‹ Î·È ÛÙÔ˘˜ ‰‡Ô

Ó‡ÌÔÓ˜ (2-14%) (2,3). ∏ ÚÒÙË ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ Ù·ÍÈÓfiÌËÛË Ù˘

™∫∞¢¶ ¤ÁÈÓ ·fi ÙÔÓ Stocker (1977), Ô ÔÔ›Ô˜ ÌÂ-ÏÂÙÒÓÙ·˜ 38 ÂÚÈÙÒÛÂȘ ™∫∞¢¶, ͯÒÚÈÛ 3 Ù‡-Ô˘˜ (π-πππ), ·Ó¿ÏÔÁ· Ì ÙË ‰È¿ÌÂÙÚÔ ÙˆÓ Î‡ÛÙˆÓÎ·È ÙÔÓ Ù‡Ô ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ô˘ ΢ÚÈ·Ú¯Ô‡Û·Ó ÛÙËÓ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË: ÙÔÓ ÌÈÎÚÔ΢ÙÙ·ÚÈÎfi ‹ Ù‡-Ô π (·ÛÙÂȘ <5 mm), ÙÔÓ ÂӉȿÌÂÛÔ ‹ Ù‡Ô ππ (·-ÛÙÂȘ 0,5-2 cm) Î·È ÙÔÓ Ì·ÎÚÔ΢ÙÙ·ÚÈÎfi ‹ Ù‡Ô πππ

∫˘ÛÙÈ΋ ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ·. ¶ÂÚÈÁÚ·Ê‹ ÙÚÈÒÓ ÂÚÈÙÒÛÂˆÓ Î·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ µ. ¢ÚfiÛÔ˘ - ∞Á·Î›‰Ô˘, ∫. ™·Ú·Ê›‰Ë˜, °. ∫˘ÚȷΛ‰Ë˜, °. ªËÙÛÈ¿ÎÔ˜, °. ∫ÚÂÌÂÓfiÔ˘ÏÔ˜

Cystic adenomatoid malformation of the lung. Report of three cases and review of the literature V. Drossou - Agakidou, K. Sarafidis, G. Kyriakidis, G. Mitsiakos, G. Kremenopoulos

∂¡¢π∞º∂ƒOÀ™∞ ¶∂ƒπ¶∆ø™∏ CASE REPORT

¡ÂÔÁÓÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞ÚÈÛÙÔÙ¤ÏÂÈÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛ-Û·ÏÔӛ΢, πÔÎÚ¿ÙÂÈÔ °¶¡ £ÂÛÛ·ÏÔӛ΢

Department of Neonatology of Aristotelion University ofThessaloniki, “Ippokration” General Hospital, Thessaloniki

�¶ÂÚ›ÏË„Ë: ∏ Û˘ÁÁÂÓ‹˜ ΢ÛÙÈ΋ ·‰Âӈ̷Ù҉˘‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ· (™∫∞¢¶) ·ÔÙÂÏ› Û¿-ÓÈÔ, ·ÏÏ¿ ÛÔ‚·Úfi ·›ÙÈÔ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·. ¶ÂÚÈÁÚ¿ÊÔÓÙ·È ÙÚÂȘ ÂÚÈÙÒ-ÛÂȘ ÓÂÔÁÓÒÓ Ì ™∫∞¢¶, ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο ÙÂÎ-ÌËÚȈ̤Ó˜. ¶ÚfiÎÂÈÙ·È ÁÈ· ‰‡Ô ÎÔÚ›ÙÛÈ· Î·È ¤Ó··ÁfiÚÈ, ‰‡Ô ·fi Ù· ÔÔ›· ÂÌÊ¿ÓÈÛ·Ó ·Ó·Ó¢ÛÙÈ΋‰˘Û¯¤ÚÂÈ· ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË Î·È ¤Ó· ÛÙÔ Ù¤-ÏÔ˜ ÙÔ˘ 1Ô˘ Ì‹Ó· Ù˘ ˙ˆ‹˜. ¶ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆ-ÛË ¤ÁÈÓ Û ̛· ÂÚ›ÙˆÛË. ªÂÙ¿ ÙË Á¤ÓÓËÛË, Ë ‰È¿-ÁÓˆÛË ‚·Û›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È ÛÙ· ¢ڋ-Ì·Ù· ÙÔ˘ ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂϤÁ¯Ô˘ (·ÎÙÈÓÔÁÚ·Ê›·ıÒڷη, ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›·). ¢ÂÓ ˘‹Ú¯·Ó ¿ÏÏÂ˜Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜. ™Â fiÏ· Ù· ÓÂÔÁÓ¿ ¤ÁÈÓ ¯ÂÈ-ÚÔ˘ÚÁÈ΋ ¤̂·ÛË (ıˆÚ·ÎÔÙÔÌ‹ Î·È ÏÔ‚ÂÎÙÔÌ‹)Û ۇÓÙÔÌÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÌÂÙ¿ ÙË ‰È¿ÁÓˆÛË. ∏‰È¿ÁÓˆÛË ÂȂ‚·ÈÒıËΠ·fi ÙËÓ ·ıÔÏÔÁÔ·Ó·ÙÔ-ÌÈ΋ ÂͤٷÛË, fiÔ˘ ‰È·ÈÛÙÒıËΠfiÙÈ ‰‡Ô ·fi ÙȘÂÚÈÙÒÛÂȘ Ì·˜ ·Ó‹Î·Ó ÛÙÔÓ Ù‡Ô 1 Î·È Ì›· ÛÙÔÓÙ‡Ô 4 Ù˘ ÓfiÛÔ˘. ∏ ÂͤÏÈÍË ‹Ù·Ó ηϋ Û ‰‡Ô ·fi·˘Ù¿ Ù· ÓÂÔÁÓ¿, ÂÓÒ ¤Ó· η٤ÏËÍ ÌÂÙÂÁ¯ÂÈÚËÙÈο·fi ÛË„·ÈÌ›·.

§¤ÍÂȘ ÎÏÂȉȿ: ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›· Ó‡ÌÔ-Ó·, Û˘ÁÁÂÓ›˜ ·ÛÙÂȘ.

�Abstract: Congenital cystic adenomatoid malfor-mation (CCAM) of the lung constitutes a rare butserious cause of neonatal respiratory distress. Threecases of histologically confirmed CCAM in newborninfants, two female and one male are reported. Twopresented with respiratory distress immediately afterbirth and one at one month of age. In one case, thecondition had been diagnosed prenatally. Postnatally,the diagnosis was made on the basis of the clinicalfeatures and the findings on radiological investigation(chest X-ray, computerized tomography). No othercongenital anomalies were found. All three neonatesunderwent lobectomy shortly after diagnosis. Thediagnosis was confirmed by histological examination,which revealed that two cases belonged to type 1 andone to type 4 CCAM. Two of the infants had a goodoutcome, whereas one died of sepsis in the immediatepostoperative period.

Key words: adenomatoid malformation of the lung,congenital cysts.

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(·ÛÙÂȘ >2 cm) (4). ŸÏÔÈ ÔÈ ·Ú·¿Óˆ Ù‡ÔÈ ·ÓÙÈ-ÛÙÔÈ¯Ô‡Û·Ó Û ‰˘ÛÏ·Û›· ÙÔ˘ ‚ÚÔÁ¯ÈÎÔ‡ ‰¤Ó-‰ÚÔ˘, ·fi ÙÔ˘˜ ÌÂÁ¿ÏÔ˘˜ ‚ÚfiÁ¯Ô˘˜ ̤¯ÚÈ Ù· ÙÂÏÈ-ο ‚ÚÔÁ¯ÈfiÏÈ· Î·È ÙÔ˘˜ ·ÂÚÒ‰ÂȘ Û¿ÎÔ˘˜, ÂÓÒ¤ÏÂÈ·Ó ÙÂÏ›ˆ˜ ·ÛÙÂȘ ΢„ÂÏȉÈ΋˜ ÚÔ¤Ï¢Û˘.∆Ô 1994, Ô Stocker ‰ËÌÔÛ›Â˘Û Ӥ· Ù·ÍÈÓfiÌËÛË, ËÔÔ›· Û˘ÌÂÚÈÂÏ¿Ì‚·Ó 5 Ù‡Ô˘˜ (Ù‡ÔÈ 0-4) (¶›-ӷη˜ 1) (5). O Ù‡Ô˜ 0 Û˘Ó‰˘¿˙ÂÙ·È Ì ÛÔ‚·Ú¤˜‰È·Ì·Úٛ˜ ÙÔ˘ ΢ÎÏÔÊÔÚÈÎÔ‡ Î·È Â›Ó·È ·Û˘Ì‚›‚·-ÛÙÔ˜ Ì ÙË ˙ˆ‹. O Ù‡Ô˜ 1 Â›Ó·È Ô Û˘¯ÓfiÙÂÚÔ˜ Ù‡-Ô˜ Î·È Ô Ù‡Ô˜ 4 Ô Û·ÓÈfiÙÂÚÔ˜, ηıÒ˜ ·Ó·Ê¤-ÚÔÓÙ·È ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· ÌfiÓÔ 3 ÙÂÎÌËÚȈ-̤Ó˜ ÂÚÈÙÒÛÂȘ ™∫∞¢¶ Ù‡Ô˘ 4 (6,7). ™˘¯Ó¿ Ë™∫∞¢¶, ȉȷ›ÙÂÚ· Ô Ù‡Ô˜ 2, Û˘Ó˘¿Ú¯ÂÈ Ì Ó¢-ÌÔÓÈÎfi ·fiÏ˘ÌÌ· (8-10).

∏ ™∫∞¢¶ ÌÔÚ› Ó· ÂΉËψı› ÚÔÁÂÓÓËÙÈοÌ ÔÏ˘-˘‰Ú¿ÌÓÈÔ Î·È ÌË ·ÓÔÛÔÏÔÁÈÎfi ‡‰Úˆ·(43%) Î·È Ó· ÚÔηϤÛÂÈ ÂÓ‰ÔÌ‹ÙÚÈÔ ı¿Ó·ÙÔ ‹ Ó·Ô‰ËÁ‹ÛÂÈ Û ÚfiˆÚÔ ÙÔÎÂÙfi (2,3). ªÂÙ¿ ÙË Á¤ÓÓË-ÛË, Ë ÓfiÛÔ˜ ÂΉËÏÒÓÂÙ·È Û˘Ó‹ıˆ˜ ÛÙË ÓÂÔÁÓÈ΋ÂÚ›Ô‰Ô Î·È Ì¿ÏÈÛÙ· ÙȘ ÚÒÙ˜ ÒÚ˜ ÌÂÙ¿ ÙË Á¤Ó-ÓËÛË, Ì ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·. ªÂÙ¿ ÙË ÓÂÔÁÓÈ-΋ ÂÚ›Ô‰Ô, ÌÔÚ› Ó· ÂΉËψı› Ì ‚‹¯· Î·È ˘Ô-ÙÚÔÈ¿˙Ô˘Û˜ ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ ‹ Ó··Ú·Ì›ÓÂÈ ·Û˘Ìو̷ÙÈ΋ ÁÈ· ÔÏÏ¿ ¯ÚfiÓÈ· Î·È Ë‰È¿ÁÓˆÛË Ó· Á›ÓÂÈ ·ÚÁfiÙÂÚ· ÛÙËÓ ÂÓ‹ÏÈÎË ˙ˆ‹(1,11,12). ™˘¯Ó¿ Û˘Ó˘¿Ú¯Ô˘Ó Î·È ¿ÏϘ Û˘ÁÁÂÓ›˜·ÓˆÌ·Ï›Â˜ ·fi ÙÔÓ Ó‡ÌÔÓ· (Ó¢ÌÔÓÈÎfi ·fiÏ˘Ì-Ì·) ‹ ·fi ¿ÏÏ· fiÚÁ·Ó·, fiˆ˜ Â›Ó·È ÔÈ ÓÂÊÚÔ› (ÓÂ-ÊÚÈ΋ ·ÁÂÓÂÛ›·, ‰˘ÛÁÂÓÂÛ›·, ΢ÛÙÈ΋ ÓfiÛÔ˜ ÙˆÓÓÂÊÚÒÓ), Ë Î·Ú‰È¿, Ù· ÔÛÙ¿, ÙÔ ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfiÛ‡ÛÙËÌ· (˘‰Ú·ÓÂÁÎÂÊ·Ï›·, ˘‰ÚÔΤʷÏÔ˜) Î·È ÙÔ¤ÓÙÂÚÔ (·ÙÚËÛ›·, Û˘ÁÁÂÓ‹˜ ‰È·ÊÚ·ÁÌ·ÙÔ΋ÏË)(2,3,10-12).

¶ÂÚÈÁÚ¿ÊÔÓÙ·È ÙÚÂȘ ÂÚÈÙÒÛÂȘ ™∫∞¢¶ Û ÓÂÔ-ÁÓ¿ Ô˘ ÓÔÛËχÙËÎ·Ó ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ Ù· ÙÂÏÂ˘Ù·›·¯ÚfiÓÈ· Î·È Á›ÓÂÙ·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜.

¶ÂÚÈÁÚ·Ê‹ ÂÚÈÙÒÛˆӶÂÚ›ÙˆÛË 1Ë ¡ÂÔÁÓfi ÎÔÚ›ÙÛÈ, Ì ËÏÈΛ· ·ËÛ˘ (∏∫) 36 ‚‰Ô-

Ì¿‰Â˜ Î·È ‚¿ÚÔ˜ Á¤ÓÓËÛ˘ (µ°) 3700 g, ‰È·ÎÔÌ›-ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ÙÔ 5Ô 24ˆÚÔ Ù˘ ˙ˆ‹˜ ÙÔ˘, ÁÈ·-Ù› ·ÚÔ˘Û›·Û ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· Ï›Á˜ÒÚ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË. ∆Ô ÎÏËÚÔÓÔÌÈÎfi ·Ó·ÌÓËÛÙÈ-Îfi ‹Ù·Ó ÂχıÂÚÔ ÁÈ· ‰˘ÛϷۛ˜ Ó‡ÌÔÓ· ‹ Û˘Á-ÁÂÓ›˜ ·ÛÙÂȘ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ Î·È ‰ÂÓ ˘‹Ú¯ÂÈÛÙÔÚÈÎfi ¤ÎıÂÛ˘ Û ‰˘ÓËÙÈο ÙÂÚ·ÙÔÁfiÓÔ˘˜ ·-Ú¿ÁÔÓÙ˜ ηٿ ÙËÓ Î‡ËÛË. ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ·ÂÌ‚Ú‡Ô˘ ÙËÓ 20Ë Â‚‰ÔÌ¿‰· Ù˘ ·ËÛ˘ ‹Ù·Ó Ê˘-ÛÈÔÏÔÁÈÎfi. ∫·Ù¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ˘, Ë ·Ï‹ ·ÎÙÈÓÔ-ÁÚ·Ê›· ıÒڷη ¤‰ÂÈÍ ¢ÌÂÁ¤ıË Î‡ÛÙË ÛÙÔ ‰ÂÍÈfiÓ¢ÌÔÓÈÎfi ‰›Ô, ¯ˆÚ›˜ ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔ-ıˆÚ·Î›Ô˘ (∂ÈÎfiÓ· 1). ¢ÂÓ ˘‹Ú¯·Ó ÂÌÊ·Ó›˜ ‰˘-ÛϷۛ˜, ÂÓÒ Ô ˘ÂÚ˯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÁÎÂ-Ê¿ÏÔ˘, ηډȿ˜ Î·È ÓÂÊÚÒÓ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ∏·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ·ÓÙÈÌÂÙˆ›ÛÙËΠ·Ú¯ÈοÌ ¯ÔÚ‹ÁËÛË Ô͢ÁfiÓÔ˘ Î·È ÙË 16Ë Ë̤ڷ ˙ˆ‹˜ ÙÔÓÂÔÁÓfi ˘Ô‚Ï‹ıËΠ۠ÏÔ‚ÂÎÙÔÌ‹ ÙÔ˘ ‰ÂÍÈÔ‡ ̤-ÛÔ˘ ÏÔ‚Ô‡ ÙÔ˘ Ó‡ÌÔÓ·. ∫·Ù¿ ÙËÓ ·ıÔÏÔÁÔ·Ó·-ÙÔÌÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠ̛· ¢ÌÂÁ¤ı˘ ·-ÛÙË Ô˘ ÂÚÈ‚·ÏÏfiÙ·Ó ·fi ΢„ÂÏ›‰Â˜, ‚ÚfiÁ¯Ô˘˜Î·È ‚ÚÔÁ¯ÈfiÏÈ· Î·È Î·Ï˘ÙfiÙ·Ó ·fi ΢ÏÈÓ‰ÚÈÎfiÎÚÔÛÛˆÙfi ÂÈı‹ÏÈÔ, Â˘Ú‹Ì·Ù· Û˘Ì‚·Ù¿ Ì ΢ÛÙÈ-΋ ·‰Âӈ̷ÙÒ‰Ë ‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ· Ù‡Ô˘1. ªÂÙ¿ ÙËÓ Â¤Ì‚·ÛË, ·Ú·ÙËÚ‹ıËΠηϋ ¤ÎÙ˘-ÍË ÙÔ˘ Ó‡ÌÔÓ·, ·ÏÏ¿ ÙÔ ÓÂÔÁÓfi η٤ÏËÍ ÙËÓ 3ËÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ë̤ڷ ·fi ÛË„·ÈÌ›·.

¶›Ó·Î·˜ 1. ¶·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÔ› Ù‡ÔÈ ™∫∞¢¶ (5)

∆‡Ô˜ 0 ∆‡Ô˜ 1 ∆‡Ô˜ 2 ∆‡Ô˜ 3 ∆‡Ô˜ 4

™˘¯ÓfiÙËÙ· (%) 1-3 >65 20-25 8 2-4

ª¤ÁÈÛÙÔ Ì¤ÁÂıԘ·ÛÙÂˆÓ (cm) 0,5 10 2,5 2 7

ªÈÎÚÔÛÎÔÈ΋ ÂÌÊ¿ÓÈÛË ¢Ô̤˜ Ô˘ ¶ÔÏ˘ÏÔ‚Ò‰ÂȘ, ªÈÎÚ¤˜, ™˘Ì·Á›˜, ¶ÔÏ˘ÏÔ‚Ò‰ÂȘ,

ÌÔÈ¿˙Ô˘Ó Ì ÌÂÁ¿Ï˜ ·ÛÙÂȘ ÔÌÔÈfiÌÔÚʘ ÔÁÎÒ‰ÂȘ ÌÂÁ¿Ï˜‚ÚfiÁ¯Ô˘˜. Ì ÈÓÒ‰Ë Î‡ÛÙÂȘ Ô˘ ‚Ï¿‚˜ Ì ÂÚÈÊÂÚÈΤ˜∫ÚÔÛÛˆÙfi, ‰È·ÊÚ¿ÁÌ·Ù·. ÌÔÈ¿˙Ô˘Ó Ì ÌÈÎÚ¤˜ ·ÛÙÂȘ.΢ÏÈÓ‰ÚÈÎfi ∫ÚÔÛÛˆÙfi ‰È·ÙÂٷ̤ӷ ·ÂÚÔÊfiÚ˜ ∫˘„ÂÏȉÈο ·ÙÙ·Ú·ÂÈı‹ÏÈÔ Ì ΢ÏÈÓ‰ÚÈÎfi ÙÂÏÈο ·ÛÙÂȘ. Ù‡Ô˘ πÎ·Ï˘ÎÔÂȉ‹ ÂÈı‹ÏÈÔ Ì ‚ÚÔÁ¯ÈfiÏÈ·. ∫ÚÔÛÛˆÙfi,·ÙÙ·Ú· ‚ÏÂÓÓÔ·Ú·ÁˆÁ¿ ∫ÚÔÛÛˆÙfi ΢‚ÔÂȉ¤˜

·ÙÙ·Ú· ΢‚ÔÂȉ¤˜ ‹ ÂÈı‹ÏÈÔ΢ÏÈÓ‰ÚÈÎfiÂÈı‹ÏÈÔ

ÃfiÓ‰ÚÔ˜ ¡·È 5%-10% Ÿ¯È Ÿ¯È Ÿ¯ÈÙˆÓ ÂÚÈÙÒÛˆÓ

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150

¶ÂÚ›ÙˆÛË 2Ë ¡ÂÔÁÓfi ÎÔÚ›ÙÛÈ, Ì ∏∫ 36 ‚‰ÔÌ¿‰Â˜ Î·È µ°

2900 g, ‰È·ÎÔÌ›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙËÁ¤ÓÓËÛË ÏfiÁˆ ‚·ÚÈ¿˜ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜.∆Ô ÎÏËÚÔÓÔÌÈÎfi ·Ó·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ Î·È‰ÂÓ ˘‹Ú¯Â ÁÓˆÛÙ‹ ¤ÎıÂÛË Û ÙÂÚ·ÙÔÁfiÓÔ˘˜ ·-Ú¿ÁÔÓÙ˜ ηٿ ÙËÓ Î‡ËÛË. ™ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ·ÙÔ˘ ÂÌ‚Ú‡Ô˘ ›¯Â ‰È·ÁÓˆÛÙ› ·ÛÙË ÛÙÔ ‰ÂÍÈfiÓ‡ÌÔÓ·, ¯ˆÚ›˜ ¿ÏÏ· ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∫·Ù¿ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó ÂÌ-Ê·Ó›˜ Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜. ™ÙËÓ ·Ï‹ ·ÎÙÈÓÔ-ÁÚ·Ê›· ıÒڷη ‰È·ÈÛÙÒıËΠ¢ÌÂÁ¤ı˘ ΢ÎÏÈ΋·ÎÙÈÓԉȷʷӋ˜ ÂÚÈÔ¯‹ ÛÙÔ ‰ÂÍÈfi Ó‡ÌÔÓ·, ÂÚÈ-‚·ÏÏfiÌÂÓË ·fi ·ÎÙÈÓÔÛÎÈÂÚfi ‰·ÎÙ‡ÏÈÔ (∂ÈÎfiÓ· 2·).O ˘ÂÚ˯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÁÎÂÊ¿ÏÔ˘, ηډȿ˜Î·È ÎÔÈÏÈ¿˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ∏ ·Ó·Ó¢ÛÙÈ΋ ‰˘-Û¯¤ÚÂÈ· ·ÓÙÈÌÂÙˆ›ÛÙËΠ̠Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi. ∆ȘÂfiÌÂÓ˜ Ë̤Ú˜ ·Ú·ÙËÚ‹ıËΠ˘ÂÚ¤ÎÙ˘ÍË ÙÔ˘‰ÂÍÈÔ‡ ¿Óˆ ÏÔ‚Ô‡ ÙÔ˘ Ó‡ÌÔÓ·, ÓÂ˘Ì·ÙÔ΋ÏËÎ·È ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ·ÚÈ-ÛÙÂÚ¿ (∂ÈÎfiÓ· 2‚). ∆Ë 17Ë Ë̤ڷ ˙ˆ‹˜, ÙÔ ÓÂÔÁÓfi˘Ô‚Ï‹ıËΠ۠ıˆÚ·ÎÔÙÔÌ‹ Î·È ÏÔ‚ÂÎÙÔÌ‹ ÙÔ˘ ‰Â-ÍÈÔ‡ ¿Óˆ Î·È Ì¤ÛÔ˘ ÏÔ‚Ô‡. ™ÙËÓ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ-΋ ÂͤٷÛË ‰È·ÈÛÙÒıËÎ·Ó Ì›· ¢ÌÂÁ¤ı˘ ·ÛÙËÛÙÔÓ ‰ÂÍÈfi ̤ÛÔ ÏÔ‚fi Î·È ‰‡Ô ÌÈÎÚfiÙÂÚ˜ ÛÙÔÓ ‰Â-ÍÈfi ¿Óˆ ÏÔ‚fi, Ô˘ ÂÚÈ‚¿ÏÏÔÓÙ·Ó ·fi ΢„ÂÏ›‰Â˜‚ÚfiÁ¯Ô˘˜ Î·È ‚ÚÔÁ¯ÈfiÏÈ· Î·È Î·Ï‡ÙÔÓÙ·Ó ·fiÎÚÔÛÛˆÙfi ΢ÏÈÓ‰ÚÈÎfi ÂÈı‹ÏÈÔ, Â˘Ú‹Ì·Ù· Û˘Ì‚·Ù¿Ì ÙÔÓ Ù‡Ô 1 ™∫∞¢¶. ∆Ô ÓÂÔÁÓfi ·Ú¤ÌÂÈÓ Û ÌË-¯·ÓÈÎfi ·ÂÚÈÛÌfi ÁÈ· 7 Ë̤Ú˜. ∫ÏÈÓÈο, Ë ·Ó·Ó¢-

ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚËÛ ÙÂÏ›ˆ˜ Î·È ÛÙËÓ ·ÎÙÈ-ÓÔÁÚ·Ê›· ıÒڷη Ô Î¿Ùˆ ÏÔ‚fi˜ ÙÔ˘ ‰ÂÍÈÔ‡ Ó‡-ÌÔÓ· ÂÎÙ‡¯ıËÎÂ Î·È Î·Ù¤Ï·‚ ÔÏfiÎÏËÚË ÙË ‰ÂÍÈ¿ıˆÚ·ÎÈ΋ ÎÔÈÏfiÙËÙ· (∂ÈÎfiÓ· 2Á). ªÂÙ¿ ÙËÓ ¤ÍÔ‰ÔÎ·È Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 4 ¯ÚfiÓˆÓ ‰ÂÓ ·ÚÔ˘Û›·Û·ӷÓ¢ÛÙÈο ÚÔ‚Ï‹Ì·Ù·.

¶ÂÚ›ÙˆÛË 3Ë¡ÂÔÁÓfi ·ÁfiÚÈ, Ì ∏∫ 31 ‚‰ÔÌ¿‰Â˜ Î·È µ° 1620

g, ·ÚÔ˘Û›·Û ‹È· ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ·Ì¤-Ûˆ˜ ÌÂÙ¿ ÙÔÓ ÙÔÎÂÙfi Î·È ‰È·ÎÔÌ›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ÙË 2Ë Ë̤ڷ ˙ˆ‹˜. ∏ ·ËÛË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋, ÙÔÔÈÎÔÁÂÓÂÈ·Îfi ·Ó·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ Î·È ‰ÂÓ·Ó·ÊÂÚfiÙ·Ó ¤ÎıÂÛË Û ÙÂÚ·ÙÔÁfiÓÔ˘˜ ·Ú¿ÁÔÓÙ˜.™ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ËÛ˘ ÁÈÓfiÙ·Ó Ù·ÎÙÈ΋ ·Ú·ÎÔ-ÏÔ‡ıËÛË Ì ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÂÌ‚Ú‡Ô˘, ÛÙÔ ÔÔ›Ô‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜ ‹ ¿ÏÏ··ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∫·Ù¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ˘, ‰ÂÓ·ÚÔ˘Û›·˙ ‰˘ÛÌÔÚÊÈο ¯·Ú·ÎÙËÚÈÛÙÈο, Ô‡Ù ¿Ï-Ϙ ÎÏÈÓÈΤ˜ ÂӉ›ÍÂȘ ‰˘ÛÌÔÚÊÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘.™ÙËÓ ·Ï‹ ·ÎÙÈÓÔÁÚ·Ê›· ıÒڷη ‰È·ÈÛÙÒıËΉȿ¯˘ÙË ‰ÈÎÙ˘ÔÎÔÎÎ҉˘ ·ÂÈÎfiÓÈÛË ÙˆÓ Ó¢Ìfi-ÓˆÓ Ì ·ÂÚÔ‚ÚÔÁ¯fiÁÚ·ÌÌ·, ‰›¯ˆ˜ ¿ÏÏ· ·ıÔÏÔÁÈ-ο Â˘Ú‹Ì·Ù·. ∆¤ıËÎÂ Ë ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ Î·È ·ÓÙÈÌÂÙˆ›ÛÙËΠ̯ÔÚ‹ÁËÛË Ì›·˜ ‰fiÛ˘ ÂÈÊ·ÓÂÈÔ‰Ú·ÛÙÈÎÔ‡ ·Ú¿-ÁÔÓÙ· Î·È Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi ÁÈ· 12 ÒÚ˜. ∏ ·Ó·-Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚËÛ ÚÔԉ¢ÙÈο ηÈÙÔ ÓÂÔÁÓfi ·Ú¤ÌÂÈÓ Û ηϋ ÁÂÓÈ΋ ηٿÛÙ·ÛË.∆ËÓ 24Ë Ë̤ڷ Ù˘ ˙ˆ‹˜ ÙÔ˘ ·ÚÔ˘Û›·Û ÂÎ Ó¤Ô˘·ÈÊÓ›‰È· ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·. ™Â ‰È·‰Ô¯ÈΤ˜·ÎÙÈÓÔÁڷʛ˜ ıÒڷη ÙȘ ÂfiÌÂÓ˜ Ë̤Ú˜ ·Ú·-ÙËÚ‹ıËΠ‚·ıÌÈ·›· ˘Âڤ΢ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡Ó‡ÌÔÓ· Ì ÔÏ˘Î˘ÛÙÈ΋ ·ÂÈÎfiÓÈÛË, ÌÂÙ·ÙfiÈÛËÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ‰ÂÍÈ¿ Î·È ·ÙÂÏÂÎÙ·Û›· ‰ÂÍÈÔ‡Ó‡ÌÔÓ· (∂ÈÎfiÓ· 3·). ™ÙËÓ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›·ÙˆÓ Ó¢ÌfiÓˆÓ ‰È·ÈÛÙÒıËÎ·Ó ÔÏϷϤ˜ ·ÂÚÈÒ-‰ÂȘ ÎÔÈÏfiÙËÙ˜ ÛÙÔÓ ·ÚÈÛÙÂÚfi ¿Óˆ ÏÔ‚fi, ·ÙÂÏÂ-ÎÙ·Û›· ÂΠȤÛˆ˜ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡, ÌÂ-Ù·ÙfiÈÛË ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ‰ÂÍÈ¿ Î·È ·ÙÂÏ‹˜¤ÎÙ˘ÍË ÙÔ˘ ‰ÂÍÈÔ‡ Ó‡ÌÔÓ· (∂ÈÎfiÓ· 3‚). ∆ËÓ 34ËË̤ڷ Ù˘ ˙ˆ‹˜ ÙÔ˘, ÙÔ ÓÂÔÁÓfi ˘Ô‚Ï‹ıËΠ۠¯ÂÈ-ÚÔ˘ÚÁÈ΋ ¤̂·ÛË, fiÔ˘ ¤ÁÈÓ ÂÎÙÔÌ‹ ÙÔ˘ ·ÚÈ-ÛÙÂÚÔ‡ ¿Óˆ ÏÔ‚Ô‡ ÙÔ˘ Ó‡ÌÔÓ·. ™ÙËÓ ·ıÔÏÔÁÔ-·Ó·ÙÔÌÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËÎ·Ó ‰È¿Û·ÚÙ˜ ·-ÛÙÂȘ ÛÙÔÓ ·ÚÈÛÙÂÚfi ÏÔ‚fi ÙÔ˘ Ó‡ÌÔÓ·, ·ÓÒÌ·Ï·ÂÚÈÁÂÁÚ·Ì̤Ó˜, Ô˘ ÂÚÈ‚¿ÏÏÔÓÙ·Ó ·fi ÏÂÙfiÈÓÔÌ˘Ò‰Â˜ ÙÔ›¯ˆÌ· Î·È Î·Ï‡ÙÔÓÙ·Ó ·fi ·ÔÏ·-Ù˘Ṳ̂ÓÔ ÌÔÓfiÛÙÈ‚Ô ÂÈı‹ÏÈÔ, Â˘Ú‹Ì·Ù· Û˘Ì‚·Ù¿Ì ÙÔÓ Ù‡Ô 4 Ù˘ ™∫∞¢¶. ªÂÙ¿ ÙËÓ Â¤Ì‚·ÛË, ÙÔÓÂÔÁÓfi ·Ú¤ÌÂÈÓ Û Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi ÁÈ· 5 Ë̤-Ú˜. ∫ÏÈÓÈο, Ë ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚË-Û ÙÂÏ›ˆ˜ Î·È ÛÙÔÓ ·ÎÙÈÓÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ‰È·ÈÛÙÒ-ıËΠÛÙ·‰È·Î‹ ¤ÎÙ˘ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡

∂ÈÎfiÓ· 1. (¶ÂÚ›ÙˆÛË 1) ∂˘ÌÂÁ¤ı˘ ·ÛÙË ÛÙÔ ‰ÂÍÈfi Ó¢ÌÔ-ÓÈÎfi ‰›Ô, ¯ˆÚ›˜ ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘.

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Î·È Î·Ù¿ÏË„Ë Ù˘ ·ÚÈÛÙÂÚ‹˜ ıˆÚ·ÎÈ΋˜ ÎÔÈÏfiÙË-Ù·˜ (∂ÈÎfiÓ· 3Á). ªÂÙ¿ ÙËÓ ¤ÍÔ‰Ô ·fi ÙËÓ ÎÏÈÓÈÎ‹Î·È Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 8 ÌËÓÒÓ, ‰ÂÓ ·ÚÔ˘Û›·Û·ӷÓ¢ÛÙÈο ÚÔ‚Ï‹Ì·Ù·.

™˘˙‹ÙËÛËOÈ ÂÚÈÙÒÛÂȘ ™∫∞¢¶ Ô˘ ÂÚÈÁÚ¿ÊÔ˘ÌÂ

¤¯Ô˘Ó Ù· ÂÍ‹˜ ¯·Ú·ÎÙËÚÈÛÙÈο: ·) Û ̛· ÌfiÓÔ Â-Ú›ÙˆÛË ˘‹Ú¯Â ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË, ·Ó Î·È˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÂÌ‚Ú‡Ô˘ ¤ÁÈÓ Û fiϘ ÙȘ ÂÚÈ-ÙÒÛÂȘ, ‚) fiϘ ÂΉËÏÒıËÎ·Ó ÛÙË ÓÂÔÁÓÈ΋ ËÏÈ-Λ·, Á) Û η̛· ‰ÂÓ ˘‹Ú¯·Ó ‰˘ÛϷۛ˜ ¿ÏψÓÔÚÁ¿ÓˆÓ Î·È ‰) ÔÈ ‰‡Ô ÂÚÈÙÒÛÂȘ ‹Ù·Ó Ù‡Ô˘ 1Î·È Ë Ì›· Ù‡Ô˘ 4.

∏ ·ıÔÁ¤ÓÂÈ· Ù˘ ™∫∞¢¶ ‰ÂÓ Â›Ó·È Ï‹Úˆ˜ÁÓˆÛÙ‹. Œ¯ÂÈ ıˆÚËı› ˆ˜ ·Ì¿Úو̷, ÂÓÙÔÈṲ̂-ÓË ‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ· Î·È ·Ó·Ù˘Íȷ΋ ‰È·-Ù·Ú·¯‹ (12). ∏ Û˘¯Ó‹ Û˘Ó‡·ÚÍË Ó¢ÌÔÓÈÎÔ‡·ÔχÌÌ·ÙÔ˜ ÂÓÈÛ¯‡ÂÈ ÙËÓ ¿Ô„Ë Ù˘ ·Ó·Ù˘ÍÈ·-

΋˜ ‰È·Ù·Ú·¯‹˜. ¶Ôχ ÚfiÛÊ·Ù·, ÔÈ MÔrotti ηÈÛ˘Ó, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ·ÓÔÛÔ˚ÛÙÔ¯ËÌÈΤ˜ ÌÂıfi-‰Ô˘˜, ÌÂϤÙËÛ·Ó ÙÔÓ Ù‡Ô ÙˆÓ Î˘ÙÙ¿ÚˆÓ 22 ÂÚÈ-ÙÒÛÂˆÓ ™∫∞¢¶ Î·È ÙÔÓ Û˘Û¯¤ÙÈÛ·Ó Ì ÙËÓ ·ıÔ-Á¤ÓÂÈ· Ù˘ ÓfiÛÔ˘ (6,13). ∫·Ù¤ÏËÍ·Ó ÛÙÔ Û˘Ì¤Ú·-ÛÌ· fiÙÈ Ë ÓfiÛÔ˜ ÔÊ›ÏÂÙ·È Û ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿-Ù˘Í˘ ÙˆÓ Ó¢ÌfiÓˆÓ Û ‰È·ÊÔÚÂÙÈΤ˜ Ê¿ÛÂȘÙ˘ ÂͤÏÈ͢ ÙÔ˘ ÙÚ·¯ÂÈÔ‚ÚÔÁ¯ÈÎÔ‡ ‰¤Ó‰ÚÔ˘. ŒÙÛÈ,ÔÈ Ù‡ÔÈ 1 ¤ˆ˜ 3 ÚÔ·ÙÔ˘Ó ·fi ·Ó·ÛÙÔÏ‹ Ù˘Ó¢ÌÔÓÈ΋˜ ·Ó¿Ù˘Í˘ ηٿ ÙË Ê¿ÛË Ù˘ ·Ó¿Ù˘-͢ ÙˆÓ ‚ÚfiÁ¯ˆÓ ̤¯ÚÈ Ù· ÙÂÏÈο ‚ÚÔÁ¯ÈfiÏÈ·(pseudocanalicular stage) Î·È ÔÈ Î‡ÛÙÂȘ ηχÙÔ-ÓÙ·È ·fi ÂÈı‹ÏÈÔ ‚ÚÔÁ¯ÈÎÔ‡ Ù‡Ô˘. O Ù‡Ô˜ 4ÔÊ›ÏÂÙ·È Û ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ Î˘„ÂÏ›-‰ˆÓ (saccular stage) Î·È ÔÈ Î‡ÛÙÂȘ ·ÚÔ˘ÛÈ¿˙Ô˘ÓÂÈı‹ÏÈÔ Î˘„ÂÏȉÈÎÔ‡ Ù‡Ô˘ (6,13).

∏ ™∫∞¢¶ ÌÔÚ› Ó· ‰È·ÁÓˆÛÙ› Ì ÙÔ ˘ÂÚ˯Ô-ÁÚ¿ÊËÌ· ÙÔ˘ ÂÌ‚Ú‡Ô˘ ·fi ÙË 17Ë Â‚‰ÔÌ¿‰· Ù˘·ËÛ˘ (3,12,14-16). ªÂ ‚¿ÛË Ù· ˘ÂÚ˯ÔÁÚ·ÊÈο

∂ÈÎfiÓ· 3. (¶ÂÚ›ÙˆÛË 3) ·) ÀÂڤ΢ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ Ó‡ÌÔÓ· Ì ÔÏ˘Î˘ÛÙÈ΋ ·ÂÈÎfiÓÈÛË, ÌÂÙ·ÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ‰Â-ÍÈ¿ Î·È ·ÙÂÏÂÎÙ·Û›· ‰ÂÍÈÔ‡ Ó‡ÌÔÓ·. ‚) ∞ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÙˆÓ Ó¢ÌfiÓˆÓ: ÔÏϷϤ˜ ·ÂÚÈÒ‰ÂȘ ÎÔÈÏfiÙËÙ˜ ÛÙÔÓ ·ÚÈÛÙÂÚfi¿Óˆ ÏÔ‚fi, ·ÙÂÏÂÎÙ·Û›· ÂΠȤÛˆ˜ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡, ÌÂÙ·ÙfiÈÛË ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ‰ÂÍÈ¿ Î·È ·ÙÂÏ‹˜ ¤ÎÙ˘ÍË ÙÔ˘‰ÂÍÈÔ‡ Ó‡ÌÔÓ·. Á) ªÂÙÂÁ¯ÂÈÚËÙÈο: ¤ÎÙ˘ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡ Î·È Î·Ù¿ÏË„Ë Ù˘ ·ÚÈÛÙÂÚ‹˜ ıˆÚ·ÎÈ΋˜ ÎÔÈÏfiÙËÙ·˜.¢È·ÎÚ›ÓÂÙ·È Ë ·ÚÔ˘Û›· ıˆÚ·ÎÈ΋˜ ·ÚÔ¯¤Ù¢Û˘.

· ‚ Á

∂ÈÎfiÓ· 2. (¶ÂÚ›ÙˆÛË 2) ·) ∂˘ÌÂÁ¤ı˘ ΢ÎÏÈ΋ ·ÎÙÈÓԉȷʷӋ˜ ÂÚÈÔ¯‹ ÛÙÔ ‰ÂÍÈfi Ó‡ÌÔÓ·, ÂÚÈ‚·ÏÏfiÌÂÓË ·fi ·ÎÙÈÓÔÛÎÈÂÚfi‰·ÎÙ‡ÏÈÔ. ‚) ªÂÙ¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ Ì˯·ÓÈÎÔ‡ ·ÂÚÈÛÌÔ‡: ˘ÂÚ¤ÎÙ˘ÍË ÙÔ˘ ‰ÂÍÈÔ‡ ¿Óˆ ÏÔ‚Ô‡ ÙÔ˘ Ó‡ÌÔÓ·, ÓÂ˘Ì·ÙÔ΋ÏË Î·È ·-ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿. Á) ªÂÙÂÁ¯ÂÈÚËÙÈο: ¤ÎÙ˘ÍË ÙÔ˘ οو ÏÔ‚Ô‡ ÙÔ˘ ‰ÂÍÈÔ‡ Ó‡ÌÔÓ·, Ô ÔÔ›Ô˜ η-٤Ϸ‚ ÔÏfiÎÏËÚË ÙË ‰ÂÍÈ¿ ıˆÚ·ÎÈ΋ ÎÔÈÏfiÙËÙ·.

· ‚ Á

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Â˘Ú‹Ì·Ù·, ‰È·ÎÚ›ÓÔÓÙ·È ‰‡Ô Ù‡ÔÈ, Ô Ì·ÎÚÔ΢ÙÙ·-ÚÈÎfi˜ Î·È Ô ÌÈÎÚÔ΢ÙÙ·ÚÈÎfi˜ (3,17), ¯ˆÚ›˜ fï˜ Ó·˘¿Ú¯ÂÈ ·ÓÙÈÛÙÔȯ›· Ì ÙÔ˘˜ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÔ‡˜Ù‡Ô˘˜ Ù˘ ÓfiÛÔ˘, Ô˘ ÂÚÈÁÚ¿ÊËÎ·Ó ·fi ÙÔÓStocker (2). ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÙÔ˘ ÂÌ‚Ú‡Ô˘ ›-Ó·È ÛËÌ·ÓÙÈÎfi fi¯È ÌfiÓÔ ÁÈ· ÙËÓ ÚÔÁÂÓÓËÙÈ΋ ‰È¿-ÁÓˆÛË, ·ÏÏ¿ Î·È ÁÈ· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ‚Ï¿-‚˘ Î·È ÙËÓ ÚfiÁÓˆÛË. ∞fi Ù· Â˘Ú‹Ì·Ù· ÙÔ˘ ˘Â-Ú˯ÔÁÚ·Ê‹Ì·ÙÔ˜ ÙÔ˘ ÂÌ‚Ú‡Ô˘, Ë ÌÈÎÚÔ΢ÛÙÈ΋ ‹·ÌÊÔÙÂÚfiÏ¢ÚË ÂÌÊ¿ÓÈÛË ÙˆÓ ‚Ï·‚ÒÓ, ÙÔ ÔÏ˘-˘‰Ú¿ÌÓÈÔ, Ô ÂÌ‚Ú˘˚Îfi˜ ‡‰Úˆ·˜ Î·È Ë ÌÂÙ·ÙfiÈÛËÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ·ÔÙÂÏÔ‡Ó ‰˘ÛÌÂÓ›˜ ÚÔÁÓˆ-ÛÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ (1-3,11,15,17,18). øÛÙfiÛÔ, ËÚÔÁÂÓÓËÙÈ΋ ηıÔ‰‹ÁËÛË Ú¤ÂÈ Ó· Á›ÓÂÙ·È Ì ÌÂ-Á¿ÏË ÚÔÛÔ¯‹, ÁÈ·Ù› ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfiÏ·Óı·Ṳ̂Ó˘ ‰È¿ÁÓˆÛ˘ ‹ ·˘ÙfiÌ·Ù˘ ‡ÊÂÛ˘. OÈMcCullagh Î·È Û˘Ó ·Ú·ÎÔÏÔ‡ıËÛ·Ó ÁÈ· ‰È¿ÛÙËÌ·25 ÌËÓÒÓ 13 ÂÚÈÙÒÛÂȘ Ì ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆ-ÛË ™∫∞¢¶ Î·È ‰È·›ÛÙˆÛ·Ó fiÙÈ Ë ÓfiÛÔ˜ ÂȂ‚·ÈÒ-ıËΠÌfiÓÔ ÛÙÔ 54% (16). ∂ÈϤÔÓ, ÔÈ Laberge ηÈÛ˘Ó, Û ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË 48 ÂÚÈÙÒÛÂˆÓ ÌÂÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶, ‚Ú‹Î·Ó fiÙÈ ÛÙÔ56% ÔÈ Î‡ÛÙÂȘ ˘Ô¯ÒÚËÛ·Ó ÛËÌ·ÓÙÈο Û ̤ÁÂıÔ˜‹ ÂÍ·Ê·Ó›ÛÙËÎ·Ó Ì¤¯ÚÈ ÙË Á¤ÓÓËÛË (1). ∫·È ¿ÏÏÔÈÛ˘ÁÁÚ·Ê›˜ ·Ó·Ê¤ÚÔ˘Ó ·˘ÙfiÌ·ÙË ÛÌ›ÎÚ˘ÓÛË ‹ÂÍ·Ê¿ÓÈÛË ÙˆÓ Î‡ÛÙÂˆÓ Ô˘ ‰È·ÁÓÒÛÙËÎ·Ó ÚÔ-ÁÂÓÓËÙÈο, Û ÔÛÔÛÙ¿ Ô˘ Î˘Ì·›ÓÔÓÙ·È ·fi 18%̤¯ÚÈ 85% (10,11,15,19). °È’ ·˘Ùfi, ÛÙȘ ÂÚÈÛÛfiÙÂ-Ú˜ ÂÚÈÙÒÛÂȘ ÚÔÁÂÓÓËÙÈ΋˜ ‰È¿ÁÓˆÛ˘ ™∫∞¢¶Û˘ÓÈÛÙ¿Ù·È ·Ú·ÎÔÏÔ‡ıËÛË ÙÔ˘ ÂÌ‚Ú‡Ô˘ Î·È Û˘-ÓÙËÚËÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË (1,10,19). ™·Ê‹ ¤Ó‰ÂÈÍË ÂÓ-‰ÔÌ‹ÙÚÈ·˜ ¯ÂÈÚÔ˘ÚÁÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘, Ë ÔÔ›·Û˘Ó›ÛÙ·Ù·È Û ıˆÚ·ÎÔ·ÌÓȷ΋ ·ÚÔ¯¤Ù¢ÛË ‹ ÏÔ-‚ÂÎÙÔÌ‹, ·ÔÙÂÏ› Ô ÂÌ‚Ú˘˚Îfi˜ ‡‰Úˆ·˜ (1,10,20).

ªÂÙ¿ ÙË Á¤ÓÓËÛË, Ë ™∫∞¢¶ ÂΉËÏÒÓÂÙ·È Û˘Ó‹-

ıˆ˜ ÙÔÓ ÚÒÙÔ Ì‹Ó· Ù˘ ˙ˆ‹˜ Ì ·Ó·Ó¢ÛÙÈ΋ ‰˘-Û¯¤ÚÂÈ· (21,15), ÁÈ· ÙËÓ ÔÔ›· ÌÔÚ› Ó· ¯ÚÂÈ·ÛÙ›Ì˯·ÓÈÎfi˜ ·ÂÚÈÛÌfi˜, Û˘Ì‚·ÙÈÎfi˜ ‹ ˘„›Û˘¯ÓÔ˜,fiˆ˜ ÛÙȘ ÂÚÈÙÒÛÂȘ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘(2,11,12,15,21). ∂›Û˘, Ë ÚÔԉ¢ÙÈ΋ ‰È¿Ù·ÛËÙˆÓ Î‡ÛÙÂˆÓ Â›Ó·È ‰˘Ó·ÙfiÓ, ›Ù ·˘ÙfiÌ·Ù· ›Ù Ïfi-Áˆ ÂÊ·ÚÌÔÁ‹˜ ıÂÙÈÎÒÓ È¤ÛˆÓ, Ó· ÚÔηϤÛÂÈ·ÙÂÏÂÎÙ·Û›· ÛÙÔ Á‡Úˆ Ó¢ÌÔÓÈÎfi ·Ú¤Á¯˘Ì·, ·-ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ Î·È ›ÂÛË ÙˆÓ Ê˘ÛÈÔ-ÏÔÁÈÎÒÓ ÏÔ‚ÒÓ ÙÔ˘ Ó‡ÌÔÓ·, Ô˘ Ô‰ËÁÔ‡Ó Û ·ÈÊ-Ó›‰È· Âȉ›ӈÛË Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜,fiˆ˜ Û˘Ó¤‚Ë ÛÙË 2Ë Î·È 3Ë ÂÚ›ÙˆÛË. ™Â fiϘ ÙȘÂÚÈÙÒÛÂȘ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘, Ë ‰È¿ÁÓˆÛËÙ˘ ÓfiÛÔ˘ ‚·Û›ÛÙËΠÛÙ· Â˘Ú‹Ì·Ù· Ù˘ ·ÎÙÈÓÔ-ÁÚ·Ê›·˜ ıÒڷη, fiÔ˘ ‰È·ÈÛÙÒıËÎ·Ó Î‡ÛÙÂȘ ÔÈ-ΛÏÔ˘ ÌÂÁ¤ıÔ˘˜ ÁÂÌ¿Ù˜ Ì ·¤Ú·. ™·ÓÈfiÙÂÚ·, ÔÈÌÈÎÚÔ΢ÛÙÈΤ˜ ‚Ï¿‚˜ (Ù‡Ô˜ 3) ÌÔÚ› Ó· ÂÌÊ·Ó›-˙ÔÓÙ·È ˆ˜ ÎÔÎÎÈÒ‰ÂȘ ‹ Û˘Ì·Á›˜ ‚Ï¿‚˜ (12). ∏·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÂȂ‚·ÈÒÓÂÈ ÙË ‰È¿ÁÓˆÛË Î·È·ÔηχÙÂÈ ÙËÓ ¤ÎÙ·ÛË Ù˘ ‚Ï¿‚˘ (12). ¶Ú¤ÂÈÓ· Á›ÓÂÙ·È Î·È ÛÙȘ ÂÚÈÙÒÛÂȘ fiÔ˘ Ë ÂÓ‰ÔÌ‹ÙÚÈ··Ú·ÎÔÏÔ‡ıËÛË ¤‰ÂÈÍ ÛÌ›ÎÚ˘ÓÛË ‹ ÂÍ·Ê¿ÓÈÛËÙˆÓ Î‡ÛÙˆÓ, ÁÈ·Ù› ÛÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜ ˘¿Ú-¯Ô˘Ó ‚Ï¿‚˜ Ô˘ ‰ÂÓ Â›Ó·È ÂÌÊ·Ó›˜ ÛÙËÓ ·Ï‹·ÎÙÈÓÔÁÚ·Ê›· ÙÔ˘ ıÒڷη Î·È ·Ô‰ÂÈÎÓ‡ÔÓÙ·È ÌfiÓÔÌ ÙËÓ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· Ó‡ÌÔÓ· (9).

O ¯ÚfiÓÔ˜ Ù˘ ¯ÂÈÚÔ˘ÚÁÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ·ÚÔ˘Û›· Û˘ÌÙˆÌ¿ÙˆÓ ·fi ÙÔ·Ó·Ó¢ÛÙÈÎfi. ∆· Û˘Ìو̷ÙÈο ÓÂÔÁÓ¿ Ì ™∫∞¢¶˘Ô‚¿ÏÏÔÓÙ·È ÁÚ‹ÁÔÚ· ÌÂÙ¿ ÙË Á¤ÓÓËÛË Û ¯ÂÈ-ÚÔ˘ÚÁÈ΋ ¤̂·ÛË, Ë ÔÔ›· Û˘Ó›ÛÙ·Ù·È Û ÏÔ‚Â-ÎÙÔÌ‹ ‹ ÙÌËÌ·ÙÂÎÙÔÌ‹ (11,12,15). °È· Ù· ·Û˘ÌÙˆ-Ì·ÙÈο ÓÂÔÁÓ¿, ÔÚÈṲ̂ÓÔÈ ˘ÔÛÙËÚ›˙Ô˘Ó fiÙÈ ı· Ú¤-ÂÈ Ó· ¯ÂÈÚÔ˘ÚÁÔ‡ÓÙ·È ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË(22,23), ÂÓÒ ¿ÏÏÔÈ ÚÔÙ›ÓÔ˘Ó ·Ú·ÎÔÏÔ‡ıËÛË Î·È

¶›Ó·Î·˜ 2. ∞ÏÁfiÚÈıÌÔ˜ ıÂڷ¢ÙÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ ÓÂÔÁÓÒÓ Ì ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶ (11)

∞Û˘Ìو̷ÙÈο ÓÂÔÁÓ¿ ™˘Ìو̷ÙÈο* ÓÂÔÁÓ¿

∞/· ıÒڷη ÛÙË Á¤ÓÓËÛË ∞/· ıÒڷη + CT ÛÙË Á¤ÓÓËÛË

∞ÚÓËÙÈ΋ ∞ÌÊ›‚ÔÏË £ÂÙÈ΋ ∞ÚÓËÙÈ΋

CT (6Ô Ì‹Ó·) CT (Á¤ÓÓËÛË) ÃÂÈÚÔ˘ÚÁÂ›Ô ∂·ÓÂÎÙ›ÌËÛË

∞ÚÓËÙÈ΋ £ÂÙÈ΋ ∞ÚÓËÙÈ΋ £ÂÙÈ΋

⁄ÊÂÛË ÃÂÈÚÔ˘ÚÁÂ›Ô ∂·ÓÂÎÙ›ÌËÛË ÃÂÈÚÔ˘ÚÁ›Ô**(6Ô Ì‹Ó·)

CT: ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ıÒڷη * ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ** Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÌÔÚ› Ó· ηı˘ÛÙÂÚ‹ÛÂÈ Ì¤¯ÚÈ ÙÔÓ 6Ô Ì‹Ó· Ù˘ ˙ˆ‹˜

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¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË ·ÚÁfiÙÂÚ·, ÌÂÙ¿ ÙËÓ ËÏÈ-Λ· ÙˆÓ 6 ÌËÓÒÓ (11). O ÚÔÙÂÈÓfiÌÂÓÔ˜ ·ÏÁfiÚÈıÌÔ˜ÁÈ· ÙË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÓÂÔÁÓÒÓ Ì ÚÔ-ÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶ Ê·›ÓÂÙ·È ÛÙÔÓ ¶›Ó·Î·2. ¶¿ÓÙˆ˜, fiÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ·fiÊ·ÛË ÁÈ· ÙÔ ¯Úfi-ÓÔ Ù˘ ¤̂·Û˘, Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È ˘’ fi„ÈÓÔÈ Î›Ó‰˘ÓÔÈ ·fi ÙËÓ Î·ı˘ÛÙÂÚË̤ÓË ·Ê·›ÚÂÛË Ù˘‚Ï¿‚˘, fiˆ˜ Â›Ó·È Ë Û˘Ì›ÂÛË ÙˆÓ Ó¢ÌfiÓˆÓ, ÔÈÏÔÈÌÒÍÂȘ, ·ÎfiÌË Î·È Ë Èı·ÓfiÙËÙ· ηÎÔ‹ıÔ˘˜ÂÍ·ÏÏ·Á‹˜ Ù˘ ‚Ï¿‚˘ (22-25).

∏ ÚfiÁÓˆÛË Ù˘ ™∫∞¢¶ Â›Ó·È Î·Ï‹ ÁÈ· ÙÔÓ Ù‡-Ô 1 Î·È ÊÙˆ¯‹ ÁÈ· ÙÔ˘˜ Ù‡Ô˘˜ 2 Î·È 3, ÂÓÒ ‰ÂÓ˘¿Ú¯Ô˘Ó ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ ÁÈ· ÙÔÓ Ù‡Ô 4(1). OÈ ÓÂÔÁÓÈÎÔ› ı¿Ó·ÙÔÈ ÔÊ›ÏÔÓÙ·È Î˘Ú›ˆ˜ ÛÙËÓÓ¢ÌÔÓÈ΋ ˘ÔÏ·Û›· ‹ ÛÙȘ ÛÔ‚·Ú¤˜ Û˘ÁÁÂÓ›˜·ÓˆÌ·Ï›Â˜ Ô˘ Û˘Ó˘¿Ú¯Ô˘Ó (1,10,21). ∏ Û˘¯Ófi-ÙËÙ· Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ Â›Ó·È ÌÂÁ¿ÏË ÛÙË™∫∞¢¶ Ù‡Ô˘ 2, ÂÚ›Ô˘ 20% (7-50%) Î·È ÌÈÎÚfiÙÂ-ÚË ÛÙÔÓ Ù‡Ô 1 (5-12,5%) (4,5,8,12). °È· ÙÔÓ Ù‡Ô 4‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹ Ë Û˘¯ÓfiÙËÙ· Û˘Ó˘·Ú¯fiÓÙˆÓÛ˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ. ™Â Ì›· ÌfiÓÔ ·fi ÙȘ ‰ËÌÔÛÈ-Â˘Ì¤Ó˜ ÂÚÈÙÒÛÂȘ ·Ó·Ê¤ÚÂÙ·È Û·ÊÒ˜ fiÙÈ ‰ÂÓ˘‹Ú¯·Ó ¿ÏϘ ‰˘ÛϷۛ˜ (7). ™ÙËÓ ÂÚ›ÙˆÛË™∫∞¢¶ Ù‡Ô˘ 4 Ô˘ ÂÚÈÁÚ¿ÊËÎÂ, ‰ÂÓ ˘‹Ú¯·Ó‰˘ÛϷۛ˜ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ Î·È Ë ¤Î‚·ÛË ‹Ù·Ó η-Ï‹. ∞Ó·ÊÔÚÈο Ì ÙË Ì·ÎÚÔ¯ÚfiÓÈ· ÚfiÁÓˆÛË ·È-‰ÈÒÓ Ì ™∫∞¢¶ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ¯ÂÈÚÔ˘ÚÁÈ΋¤̂·ÛË, ·˘Ù‹ Â›Ó·È Î·Ï‹, ηıÒ˜ ÌÂÙ¿ ·fi ÙË ÏÔ-‚ÂÎÙÔÌ‹ ‚ÂÏÙÈÒÓÂÙ·È Ë Ó¢ÌÔÓÈ΋ ÏÂÈÙÔ˘ÚÁ›·, ·-Ú¿ Ù· ‹È· ·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù· Ô˘ ÌÔÚ› Ó·˘¿Ú¯Ô˘Ó, fiˆ˜ Â›Ó·È ÙÔ ·ÓÙÈÛÙ·ıÌÈÛÙÈÎfi ÂÌʇÛË-Ì· (26). ™Ô‚·Ú‹ ÂÈÏÔ΋ Ì·ÎÚÔÚfiıÂÛÌ· ·ÔÙÂ-Ï› Ë “˘ÔÏÂÈÌÌ·ÙÈ΋” ™∫∞¢¶, ‰ËÏ·‰‹ Ë fi„ÈÌË ÂÌ-Ê¿ÓÈÛË Û˘ÌÙˆÌ¿ÙˆÓ Ô˘ ÔÊ›ÏÔÓÙ·È Û ÌÈÎÚÔ΢-ÛÙÈΤ˜ ‚Ï¿‚˜, ÔÈ Ôԛ˜ ‰ÂÓ ¤ÁÈÓ·Ó ·ÓÙÈÏËÙ¤˜ÛÙÔÓ ·Ú¯ÈÎfi ¤ÏÂÁ¯Ô ηÈ, ηٿ Û˘Ó¤ÂÈ·, ‰ÂÓ ·Ê·È-Ú¤ıËÎ·Ó Ì ÙËÓ ·Ú¯È΋ ¤̂·ÛË (26). OÈ ‰‡Ô·ÛıÂÓ›˜ Ô˘ ¤˙ËÛ·Ó ÌÂÙ¿ ÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô,Û‹ÌÂÚ· ËÏÈΛ·˜ 4 ÂÙÒÓ Î·È 8 ÌËÓÒÓ ·ÓÙ›ÛÙÔȯ·, ‰ÂÓ·ÚÔ˘Û›·Û·Ó ·Ó·Ó¢ÛÙÈο ÚÔ‚Ï‹Ì·Ù·.

™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ™∫∞¢¶, ·Ó Î·È ·ÔÙÂÏ›ۿÓÈ· ·ÈÙ›· ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ ÛÙË ÓÂÔ-ÁÓÈ΋ ËÏÈΛ·, ··ÈÙ› ¿ÌÂÛË ·Ó·ÁÓÒÚÈÛË, ηıÒ˜ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ¤¯ÂÈ Î·Ï‹ ÚfiÁÓˆ-ÛË ÌÂÙ¿ ·fi ¤ÁηÈÚË ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË.∂›Û˘, ·fi Ù· Â˘Ú‹Ì·Ù· Ù˘ ÂÚ›ÙˆÛ˘ ™∫∞¢¶Ù‡Ô˘ 4 ÚÔÛÙ›ıÂÓÙ·È ÂӉ›ÍÂȘ ÛÙ· ‹‰Ë ˘¿Ú¯ÔÓÙ·Û¿ÓÈ· ‰Â‰Ô̤ӷ Û¯ÂÙÈο Ì ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ô Ù‡-Ô˜ ·˘Ùfi˜ ‰ÂÓ Û˘Ó‰˘¿˙ÂÙ·È Ì ¿ÏϘ ‰˘ÛϷۛ˜.

µÈ‚ÏÈÔÁÚ·Ê›·1. Laberge JM, Flageole H, Pugash D, Khalife S, Blair G,

Filiatrault D et al. Outcome of the prenatally diagnosedcongenital cystic adenomatoid lung malformation: a

Canadian experience. Fetal Diagn Ther 2001;16:178-186. 2. Miller JA, Corteville JE, Langer JC. Congenital cystic

adenomatoid malformation in the fetus: natural history andpredictors of outcome. J Pediatr Surg 1996;31:805-808.

3. Thorpe-Beeston JG, Nicolaides KH. Cystic adenomatoidmalformation of the lung: prenatal diagnosis and outcome.Prenat Diagn 1994;14:677-688.

4. Stocker JT, Madewell JE, Drake RM. Congenital cysticadenomatoid malformation of the lung. Classification andmorphologic spectrum. Hum Pathol 1977;8:155-171.

5. Stocker JT. Congenital and developmental diseases. In:Dail DH, Hammer SP, editors. Pulmonary Pathology. 2nded. New York: Springer; 1994. p. 174-180.

6. Morotti RA, Cangiarella J, Gutierrez MC, Jagirdar J, Askin F,Singh G et al. Congenital cystic adenomatoid malformationof the lung (CCAM): evaluation of the cellular components.Hum Pathol 1999;30:618-625.

7. van Koningsbruggen S, Ahrens F, Brockmann M, MichalkD, Rietschel E. Congenital cystic adenomatoidmalformation type 4. Pediatr Pulmonol 2001;32:471-475.

8. Conran RM, Stocker JT. Extralobar sequestration withfrequently associated congenital cystic adenomatoidmalformation, type 2: report of 50 cases. Pediatr Dev Pathol1999;2:454-463.

9. Winters WD, Effmann EL, Nghiem HV, Nyberg DA.Disappearing fetal lung masses: importance of postnatalimaging studies. Pediatr Radiol 1997;27:535-539.

10. Roggin KK, Breuer CK, Carr SR, Hansen K, KurkchubascheAG, Wesselhoeft CW Jr et al. The unpredictable characterof congenital cystic lung lesions. J Pediatr Surg2000;35:801-805.

11. Bagolan P, Nahom A, Giorlandino C, Trucchi A, BilancioniE, Inserra A et al. Cystic adenomatoid malformation of thelung: clinical evolution and management. Eur J Pediatr1999;158:879-882.

12. Waszak P, Claris O, Lapillonne A, Picaud JC, Basson E,Chappuis JP et al. Cystic adenomatoid malformation of thelung: neonatal management of 21 cases. Pediatr Surg Int1999;15:326-331.

13. Morotti RA, Gutierrez MC, Askin F, Profitt SA, Wert SE,Whitsett JA et al. Expression of thyroid transcription factor-1 in congenital cystic adenomatoid malformation of thelung. Pediatr Dev Pathol 2000;3:455-461.

14. Mahle WT, Rychik J, Tian ZY, Cohen MS, Howell LJ,Crombleholme TM et al. Echocardiographic evaluation ofthe fetus with congenital cystic adenomatoid malformation.Ultrasound Obstet Gynecol 2000;16:620-624.

15. Sapin E, Lejeune VV, Barbet JP, Carricaburu E, Lewin F,Baron JM et al. Congenital adenomatoid disease of thelung: prenatal diagnosis and perinatal management.Pediatr Surg Int 1997;12:126-129.

16. McCullagh M, MacConnachie I, Garvie D, Dykes E.Accuracy of prenatal diagnosis of congenital cysticadenomatoid malformation. Arch Dis Child 1994;71:F111-113.

17. Adzick NS, Harrison MR, Glick PL, Golbus MS, AndersonRL, Mahony BS et al. Fetal cystic adenomatoidmalformation: prenatal diagnosis and natural history. JPediatr Surg 1985;20:483-488.

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18. Bunduki V, Ruano R, da Silva MM, Miguelez J, Miyadahira S,Maksoud JG et al. Prognostic factors associated withcongenital cystic adenomatoid malformation of the lung.Prenat Diagn 2000;20:459-464.

19. Monni G, Paladini D, Ibba RM, Teodoro A, Zoppi MA,Lamberti A et al. Prenatal ultrasound diagnosis of congenitalcystic adenomatoid malformation of the lung: a report of 26cases and review of the literature. Ultrasound ObstetGynecol 2000;16:159-162.

20. Dommergues M, Louis-Sylvestre C, Mandelbrot L, AubryMC, Revillon Y, Jarreau PH et al. Congenital adenomatoidmalformation of the lung: when is active fetal therapyindicated? Am J Obstet Gynecol 1997;177:953-958.

21. Neilson IR, Russo P, Laberge JM, Filiatrault D, Nguyen LT,Collin PP et al. Congenital adenomatoid malformation of thelung: current management and prognosis. J Pediatr Surg1991;26:975-980.

22. Marshall KW, Blane CE, Teitelbaum DH, van Leeuwen K.Congenital cystic adenomatoid malformation: impact ofprenatal diagnosis and changing strategies in the treatmentof the asymptomatic patient. Am J Roentgenol2000;175:1551-1554.

23. dell’Agnola C, Tadini B, Mosca F, Colnaghi M, Wesley J.Advantages of prenatal diagnosis and early surgery forcongenital cystic disease of the lung. J Perinat Med1996;24:621-631.

24. Shariff S, Thomas JA, Shetty N, D’Cunha S. Primarypulmonary rhabdomyosarcoma in a child, with a review ofliterature. J Surg Oncol 1988;38:261-264.

25. Sheffield EA, Addis BJ, Corrin B, McCabe MM. Epithelialhyperplasia and malignant change in congenital lung cysts.J Clin Pathol 1987;40:612-614.

26. Frenckner B, Freyschuss U. Pulmonary function afterlobectomy for congenital lobar emphysema and congenitalcystic adenomatoid malformation. A follow-up study. ScandJ Thorac Cardiovasc Surg 1982;16:293-298.

HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-11-2002 HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 17-02-2003

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: µ·ÛÈÏÈ΋ ¢ÚfiÛÔ˘-∞Á·Î›‰Ô˘ °ÏËÓÔ‡ 28, ∆.∫. 543 52, £ÂÛÛ·ÏÔÓ›ÎËE-mail: agaki@med.auth.gr

∂ÈÛ·ÁˆÁ‹: ∏ Îڤ̷ pimecrolimus 1% (Elidel, SDZ ASM 981)Â›Ó·È ÌË ÛÙÂÚÈÓÔÂȉ‹˜ ÂÎÏÂÎÙÈÎfi˜ ·Ó·ÛÙÔϤ·˜ ÙˆÓ ÊÏÂÁÌÔÓˆ-‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ, Ô˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÙÔÈο ÛÙË ıÂڷ›·Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜. ∏ ·ÚÔ‡Û· ÌÂϤÙË ‰ÈÂÚÂ˘Ó¿ ÙËÓ›‰Ú·ÛË Ù˘ ÚÒÈÌ˘ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ Ì Îڤ̷pimecrolimus ÛÙË Ì·ÎÚÔ¯ÚfiÓÈ· ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘.™ÎÔfi˜: ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ó· ·ÍÈÔÏÔÁ‹ÛÂÈ ·Ó Ë ÚÒÈ-ÌË ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË Ì pimecrolimus Û ‚Ú¤ÊË Ì·ÙÔÈ΋ ‰ÂÚÌ·Ù›Ùȉ· ÌÔÚ› Ó· ÂËÚ¿ÛÂÈ ÙË Ì·ÎÚÔ¯ÚfiÓÈ·ÔÚ›· Ù˘ ÓfiÛÔ˘, ÚÔÏ·Ì‚¿ÓÔÓÙ·˜ ÙȘ ÂÍ¿ÚÛÂȘ.ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ¶Ú·ÁÌ·ÙÔÔÈ‹ıËΠ̛· ‰ÈÏ‹-Ù˘ÊÏ‹ ÌÂ-ϤÙË, ‰È¿ÚÎÂÈ·˜ ÂÓfi˜ ¤ÙÔ˘˜, Û 251 ‚Ú¤ÊË ËÏÈΛ·˜ 3-23 ÌËÓÒÓÔ˘ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Ì ÏfiÁÔ 4:1 Û ‰‡Ô ıÂڷ¢ÙÈΤ˜ ÔÌ¿-‰Â˜: ÛÙËÓ ÚÒÙË ÂÊ·ÚÌfiÛÙËΠÛ··ÛÌ· pimecrolimus(n=204) Î·È ÛÙË ‰Â‡ÙÂÚË Û˘Ì‚·ÙÈ΋ ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹(n=47). ∫·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ ÂÈÙÚÂfiÙ·Ó Ë ¯Ú‹ÛË Ì·Ï·ÎÙÈ-ÎÒÓ ÁÈ· ÙËÓ ÍËÚÔ‰ÂÚÌ›· Î·È ÙÔÈÎÒÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÁÈ·ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ Ù˘ ÓfiÛÔ˘. ™ÙËÓ ÂÚ›ÙˆÛËÚÒÈÌˆÓ ÛËÌ›ˆÓ Î·È Û˘ÌÙˆÌ¿ÙˆÓ ‰ÂÚÌ·Ù›Ùȉ·˜, ¯ÚËÛÈÌÔ-ÔÈ‹ıËΠÎڤ̷ pimecrolimus ‹ ÌfiÓÔ ¤Î‰Ô¯Ô. ∏ ·ÔÙÂÏÂ-ÛÌ·ÙÈÎfiÙËÙ· Ù˘ ÂÊ·ÚÌÔ˙fiÌÂÓ˘ ·ÁˆÁ‹˜ ÂÎÙÈÌ‹ıËΠ̠‚¿-ÛË ÙËÓ Â›ÙˆÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ ÛÙÔ˘˜ 6 Ì‹Ó˜ ·fi ÙËÓ ¤Ó·Ú-ÍË Ù˘ ıÂڷ›·˜. ∞ÔÙÂϤÛÌ·Ù·: ¢È·ÈÛÙÒıËΠfiÙÈ ÙÔ pimecrolimus Ô‰‹ÁËÛÂÛ ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›ÙÈ-‰·˜ Î·È ‹Ù·Ó ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈÎfi ÛÙÔÓ Ì·ÎÚÔ¯ÚfiÓÈÔ ¤ÏÂÁ¯ÔÙÔ˘ ÎÓËÛÌÔ‡ Î·È ÙˆÓ ˘fiÏÔÈˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Ù˘ ÓfiÛÔ˘, ÛÂÛ‡ÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘, Ì ÔÛÔÛÙfi 67,6% ÙˆÓ

·ÛıÂÓÒÓ Ó· ÔÏÔÎÏËÚÒÓÂÈ ÙÔ ÂÍ¿ÌËÓÔ Ù˘ ÌÂϤÙ˘ ¯ˆÚ›˜ η-Ì›· ¤Í·ÚÛË, Û ۯ¤ÛË Ì 34,8% ÙˆÓ Ì·ÚÙ‡ÚˆÓ (p<0,001), ÂÓÒ56,9% ¤Ó·ÓÙÈ 28,3%, ·ÓÙ›ÛÙÔȯ·, ¯ˆÚ›˜ ¤Í·ÚÛË Î·Ù¿ ÙË ‰È¿Ú-ÎÂÈ· ÂÓfi˜ ¤ÙÔ˘˜. ∂ÈϤÔÓ, Ë ¯Ú‹ÛË ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓÛÙËÓ ÔÌ¿‰· ÙÔ˘ pimecrolimus ‹Ù·Ó ·ÈÛıËÙ¿ ÂÚÈÔÚÈṲ̂ÓË:63,7% ÙˆÓ ·ÛıÂÓÒÓ ‰ÂÓ ¯ÚËÛÈÌÔÔ›ËÛ ηıfiÏÔ˘ ÛÙÂÚÔÂȉ‹,Û ۯ¤ÛË Ì 34,8% ÙˆÓ Ì·ÚÙ‡ÚˆÓ. ∆Ô pimecrolimus ‹Ù·Ó ›-Û˘ ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈÎfi ÛÙÔÓ ¤ÏÂÁ¯Ô ÙÔ˘ ÎÓËÛÌÔ‡ Î·È ÙˆÓ ÛË-Ì›ˆÓ Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜. ¢ÂÓ ̆ ‹Ú¯·Ó ÛÙ·ÙÈÛÙÈο ÛË-Ì·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ fiÛÔÓ ·ÊÔÚ¿ ÛÙȘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ. ™˘ÌÂÚ¿ÛÌ·Ù·: ∏ ıÂڷ›· ÙˆÓ ÚÒÈÌˆÓ ÛËÌ›ˆÓ Î·È Û˘-ÌÙˆÌ¿ÙˆÓ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜ Ì pimecrolimus ÌÔÚ›ӷ ·ÏÏ¿ÍÂÈ ÛËÌ·ÓÙÈο ÙËÓ ÔÚ›· Ù˘ ÓfiÛÔ˘, ÌÂÈÒÓÔÓÙ·˜ ÙȘÂÍ¿ÚÛÂȘ Î·È ‚ÂÏÙÈÒÓÔÓÙ·˜ ÙÔÓ ÁÂÓÈÎfi ¤ÏÂÁ¯Ô Ù˘ ÓfiÛÔ˘. ∆Ôpimecrolimus ‹Ù·Ó ·ÛʷϤ˜ Î·È Î·Ï¿ ·ÓÂÎÙfi.

ª·ÎÚÔ¯ÚfiÓÈ· ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜ Û ‚Ú¤ÊË, Ì ÙÔÈ΋ ÂÊ·ÚÌÔÁ‹ pimecrolimus1

¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›·

1Kapp A, Papp K, Bingham A, Folster-Holst R,Ortonne JP, Potter PC et al Long-term management of atopic dermatitis ininfants with topical pimecrolimus, a nonsteroid anti-inflammatory drug J Allergy Clin Immunol 2002;110:277-284

∂ϤÓË µÔÏÔÓ¿ÎË

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§Â˘ÎÔÙÚȤÓÈ· Î·È ÊÏÂÁÌÔÓ‹: ÓÂfiÙÂÚË Ê·ÚÌ·ÎÔÏÔÁÈ΋ ıÂÒÚËÛË ∞. ∆˘ÏÈÁ¿‰·, °. ∞ÓÙˆÓÔÁÂÒÚÁÔ˜

Leukotrienes and inflammation: current pharmacological perspective ∂. Tiligada, G. Antonogeorgos

∂¶π∫∞πƒ∞ £∂ª∞∆∞ CURRENT ISSUES

�¶ÂÚ›ÏË„Ë: ∆· Ï¢ÎÔÙÚȤÓÈ· (L∆s) Â›Ó·È ÂÓ‰ÔÁÂ-Ó›˜ ÏÈȉÈÎÔ› ÌÂÛÔÏ·‚ËÙ¤˜ Ô˘ Û˘ÓÙ›ıÂÓÙ·È denovo Ì ‰È·Î˘ÙÙ¿ÚÈÔ ÌÂÙ·‚ÔÏÈÛÌfi, ̤ۈ Ù˘ Ô‰Ô‡Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘. ™˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ıÔÁ¤-ÓÂÈ· ÙÔ˘ ¿ÛıÌ·ÙÔ˜ Î·È ¿ÏÏˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓ ‰È·‰È-ηÛÈÒÓ Î·È ÛÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈÛÙ‹. OÌ·‰ÔÔÈÔ‡-ÓÙ·È Û ΢ÛÙÂ˚Ó˘ÏÈο ·Ó¿ÏÔÁ· (cys-LTs) Î·È ÛÙÔLTB4 Î·È ·ÛÎÔ‡Ó ÙË ‰Ú¿ÛË ÙÔ˘˜ ̤ۈ ‰È·ÎÚÈÙÒÓ˘ÔÙ‡ˆÓ ˘Ô‰Ô¯¤ˆÓ. ™ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiË-ÛË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· Ê·ÚÌ·ÎÔÏÔÁÈο ¯·Ú·ÎÙËÚÈ-ÛÙÈο Ù˘ Û‡ÓıÂÛ˘, ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Î·È Ù˘‰Ú¿Û˘ ÙˆÓ L∆s, ÔÈ È‰ÈfiÙËÙ˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘˜Î·È Ë ÎÏÈÓÈ΋ ÂÊ·ÚÌÔÁ‹ ÙˆÓ ÙÚÔÔÔÈËÙÒÓ ÙˆÓÏ¢ÎÔÙÚÈÂÓ›ˆÓ.

§¤ÍÂȘ ÎÏÂȉȿ: Ï¢ÎÔÙÚȤÓÈ·, ˘Ô‰Ô¯Â›˜, ÙÚÔÔ-ÔÈËÙ¤˜.

�Abstract: Leukotrienes (L∆s) are endogenouslipid mediators, which are synthesised de novo viaintercellular metabolic processes, through the 5-lipoxygenase pathway. ∆hey are involved in thepathogenesis of asthma and other inflammatoryprocesses and in the host defence response. Theyare sub-grouped into cysteinyl-LTs (cys-LTs) andLTB4 and exert their action via distinct receptors.This review presents the pharmacologicalcharacteristics of the synthesis, metabolism andaction of LTs, the properties of their receptors andthe clinical application of the leukotriene modifiers.

Key words: leukotrienes, receptors, modifiers.

∂ÚÁ·ÛÙ‹ÚÈÔ º·ÚÌ·ÎÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ

Laboratory of Pharmacology, Medical School of University of Athens

™˘ÓÙÔÌÔÁڷʛ˜AIA ÕÛıÌ· ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ·ÛÈÚ›Ó˘ BLT ÀÔ‰Ô¯¤·˜ ÙÔ˘ Ï¢ÎÔÙÚÈÂÓ›Ô˘ µ4

cPLA2 ∫˘ÙÔÛÔÏÈ΋ ʈÛÊÔÏÈ¿ÛË ∞2

cysLT(s) ∫˘ÛÙÂ˚Ó˘ÏÈÎfi(¿) Ï¢ÎÔÙÚȤÓÈÔ(·) FLAP ¶ÚˆÙ½ÓË ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘ GPCR ÀÔ‰Ô¯¤·˜ Û˘Ó‰ÂfiÌÂÓÔ˜ Ì ڈÙ½Ó˜ G 5-HpETE 5-˘‰ÚÔÂÚÔ͢-ÂÈÎÔÛ·ÙÂÙÚ·ÓÔ˚Îfi Ô͇ IL πÓÙÂÚÏ¢ΛÓË 5-LO 5-ÏÈÔ͢ÁÂÓ¿ÛË LT(s) §Â˘ÎÔÙÚȤÓÈÔ(·) MAP ¶ÚˆÙ½ÓË ÂÓÂÚÁÔÔÈÔ‡ÌÂÓË ·fi ÌÈÙÔÁfiÓ· MAPK ∫ÈÓ¿ÛË Ù˘ ª∞ƒ ORF ¶Ï·›ÛÈÔ ·Ó¿ÁÓˆÛ˘ PAF ¶·Ú¿ÁÔÓÙ·˜ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ PGE2 ¶ÚÔÛÙ·ÁÏ·Ó‰›ÓË ∂2

ROS ∂ÓÂÚÁ¿ ·Ú¿ÁˆÁ· Ô͢ÁfiÓÔ˘ SRS µÚ·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›·

SRS-A µÚ·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›· Ù˘ ·Ó·Ê˘Ï·Í›·˜ 7TM ∂Ù¿ ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ ÂÚÈÔ¯¤˜ TNF OÁÎÔÓÂÎÚˆÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜

∂ÈÛ·ÁˆÁ‹¶ÚÈÓ 60 ¯ÚfiÓÈ·, ‹Ù·Ó ÁÓˆÛÙfi fiÙÈ Ì›· ‚Ú·‰¤ˆ˜-

·ÓÙȉÚÒÛ· Ô˘Û›· (SRS, slow-reacting substance),ÂÎÏ˘fiÌÂÓË ·fi ÙÔ˘˜ Ó‡ÌÔÓ˜ ÌÂÙ¿ ·fi ·ÓÙÈÁÔÓÈ-΋ ‰È¤ÁÂÚÛË, ›¯Â ÙËÓ ÈηÓfiÙËÙ· Ó· Û˘Û¿ ÙÔ˘˜ Ï›-Ô˘˜ Ì˘˜ (1). ∂›ÎÔÛÈ ¯ÚfiÓÈ· ·ÚÁfiÙÂÚ·, ÌÂÙÔÓÔÌ¿-ÛÙËΠ۠‚Ú·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›· Ù˘ ·Ó·Ê˘Ï·-Í›·˜ (SRS-A, slow-reacting substance of anaphyla-xis), ÂÂȉ‹ Ë ·Ú·ÁˆÁ‹ Ù˘ Û¯ÂÙÈ˙fiÙ·Ó Ì ÙËÓ ·Â-Ï¢ı¤ÚˆÛË ÈÛÙ·Ì›Ó˘ ηٿ ÙÔ ·Ó·Ê˘Ï·ÎÙÈÎfi ÛÔÎ(2). ∆Ô 1979, Ë SRS-A Ù·˘ÙÔÔÈ‹ıËÎÂ Î·È ÔÓÔÌ¿-ÛÙËΠϢÎÔÙÚȤÓÈÔ (LT), ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÙÔ ÌfiÚÈÔ‹Ù·Ó ‰ÔÌÈο Û˘ÁÁÂÓ¤˜ Ì ٷ ÌÂÙ·‚ÔÏÈο ÚÔ˚fiÓÙ·ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ Ôͤˆ˜ ÛÙ· Ï¢ÎÔ·ÙÙ·Ú· ηÈ

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ÂÚÈ›¯Â ¤Ó· Û˘˙¢Á̤ÓÔ ÙÚȤÓÈÔ (3). ∆Ô LTC ‹Ù·Ó ÙÔÂÈÎÔÛ·ÓÔÂȉ¤˜ Ô˘ Ù·˘ÙÔÔÈ‹ıËΠ(3), ÂÓÒ ÙËÓ ›‰È·ÂÔ¯‹ ·ÔÌÔÓÒıËÎÂ Î·È ÙÔ LTB4 ·fi Ù· ÔÏ˘ÌÔÚ-ÊÔ‡ÚËÓ· Ï¢ÎÔ·ÙÙ·Ú· (4). ª¤¯ÚÈ Û‹ÌÂÚ·, Ë ÂÚ¢-ÓËÙÈ΋ ÚÔÛ¿ıÂÈ· ÛÙÔÓ ÙÔ̤· ·˘Ùfi ÂÈÎÂÓÙÚÒıËÎÂÛÙÔ ÌÂÛÔÏ·‚ËÙÈÎfi ÚfiÏÔ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ ÛÙÔ¿ÛıÌ· ηÈ, ÁÂÓÈÎfiÙÂÚ·, ÛÙȘ ·ÓÙȉڿÛÂȘ ˘ÂÚ¢·È-ÛıËÛ›·˜ Û ·ÓıÚÒÈÓÔ˘˜ Î·È ¿ÏÏÔ˘˜ ˙ˆÈÎÔ‡˜ ÈÛÙÔ‡˜in vitro Î·È in vivo (4-6). ∂›Ó·È ϤÔÓ ·Ô‰ÂÎÙfi fiÙÈ Ù·Ï¢ÎÔÙÚȤÓÈ· Â›Ó·È ÂÓ‰ÔÁÂÓ›˜ ÏÈȉÈÎÔ› ÌÂÛÔÏ·‚ËÙ¤˜Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙË ÌÂÙ·ÁˆÁ‹ ÙˆÓ ÛËÌ¿ÙˆÓ Î·ÈÛÙË ‰È·Î˘ÙÙ¿ÚÈ· ÂÈÎÔÈÓˆÓ›· ηٿ ÙË ÊÏÂÁÌÔÓ҉˷¿ÓÙËÛË Î·È ÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈÛÙ‹ (6,7).

∆· Ï¢ÎÔÙÚȤÓÈ· ÔÌ·‰ÔÔÈÔ‡ÓÙ·È Ì ‚¿ÛË ÙË ¯Ë-ÌÈ΋ ‰ÔÌ‹ Î·È ÙË ‚ÈÔÏÔÁÈ΋ ÙÔ˘˜ ‰Ú¿ÛË Û ‰‡ÔÔÌ¿‰Â˜, Ë Ì›· ÂÎ ÙˆÓ ÔÔ›ˆÓ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ ÚÔ-ÊÏÂÁÌÔÓ҉˜ ‰È¸‰ÚÔ͢-Ï¢ÎÔÙÚȤÓÈÔ LTB4 Î·È Ë ¿Ï-ÏË Ù· ÂÙȉÔÏÈȉÈο ‹ ÛÔ˘ÏÊȉÈο ‹ ΢ÛÙÂ˚Ó˘ÏÈοÏ¢ÎÔÙÚȤÓÈ· (cysLTs) LTC4, LTD4 Î·È LTE4. OÈ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ cysLTs ¤¯Ô˘Ó ‹‰Ë ‚ÚÂÈ ÎÏÈÓÈ΋ÂÊ·ÚÌÔÁ‹ ÛÙË ıÂڷ¢ÙÈ΋ ÙÔ˘ ¿ÛıÌ·ÙÔ˜.

™‡ÓıÂÛË Î·È ÌÂÙ·‚ÔÏÈÛÌfi˜ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ ∏ ·Ú·ÁˆÁ‹ ÙˆÓ ÂÈÎÔÛ·ÓÔÂȉÒÓ Ú·ÁÌ·ÙÔÔÈ-

Â›Ù·È ÛÙËÓ ˘ÚËÓÈ΋ ÌÂÌ‚Ú¿ÓË. ∆· Ï¢ÎÔÙÚȤÓÈ·‰ÂÓ ·ÔıË·ÔÓÙ·È ÛÙ· ·ÙÙ·Ú·, ·ÏÏ¿ ‚ÈÔÛ˘ÓÙ›ıÂ-ÓÙ·È de novo (∂ÈÎfiÓ· 1) (5,8), fiÙ·Ó Ë Ca2+-ÂÍ·ÚÙÒ-ÌÂÓË Î˘ÙÔÛÔÏÈ΋ ʈÛÊÔÏÈ¿ÛË ∞2 (cPLA2) ÌÂÙ·-ÙÔ›˙ÂÙ·È ÛÙÔÓ ˘ÚËÓÈÎfi Ê¿ÎÂÏÔ ÌÂÙ¿ ·fi ‰È¤ÁÂÚ-ÛË Î·È ·ÂÏ¢ıÂÚÒÓÂÈ ·Ú·¯È‰ÔÓÈÎfi Ô͇ ·fi Ù·ÌÂÌ‚Ú·ÓÈο ʈÛÊÔÏÈ›‰È· (9). µ·ÛÈÎfi ÚfiÏÔ ÛÙÔÛ¯ËÌ·ÙÈÛÌfi ÙˆÓ LTs ·›˙ÂÈ Ë 5-ÏÈÔ͢ÁÂÓ¿ÛË (5-LO), Ì›· Ca2+-ÂÍ·ÚÙÒÌÂÓË Î˘ÙÔÛÔÏÈ΋ ÚˆÙ½ÓË.ªÂÙ¿ ·fi ΢ÙÙ·ÚÈ΋ ‰È¤ÁÂÚÛË, Ë 5-LO ʈÛÊÔÚ˘-ÏÈÒÓÂÙ·È Èı·ÓÒ˜ ̤ۈ Ù˘ MAPK-1 (mitogen-activated protein kinase), ÌÂÙ·ÙÔ›˙ÂÙ·È ÛÙÔÓ ˘ÚË-ÓÈÎfi Ê¿ÎÂÏÔ, ·Á΢ÚÔ‚ÔÏ› ÛÙË ÌÂÌ‚Ú¿ÓË Î·È Ì¤ÛˆÙ˘ ÚˆÙ½Ó˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿-Û˘ (FLAP) ÌÂÙ·ÙÚ¤ÂÈ ÙÔ ·Ú·¯È‰ÔÓÈÎfi Ô͇ ·Ú¯ÈοÛ 5-˘‰ÚÔ͢-ÂÚÔ͢-ÂÈÎÔÛ·ÙÂÙÚ·ÓÔ˚Îfi Ô͇ (5-HpETE) Î·È Î·ÙfiÈÓ ÙÔ ·Ê˘‰·ÙÒÓÂÈ Û LT∞4 (5,6-ÔÍÂȉÔ-7,9-trans-11,14-cis-ÂÈÎÔÛ·ÙÂÙÚ·ÓÔ˚Îfi Ô͇)(10,11). ∏ 5-LO ·ÂÓÂÚÁÔÔÈÂ›Ù·È Ì ÌË ·Ó·ÛÙÚ¤-„ÈÌË Û‡Ó‰ÂÛË ÙÔ˘ ‰Ú·ÛÙÈÎÔ‡ ÚÔ˚fiÓÙÔ˜ Ù˘ LT∞4.∆Ô LT∞4 Â›Ó·È ·ÛÙ·ı¤˜ Î·È ÌÂÙ·ÙÚ¤ÂÙ·È Ù·¯¤ˆ˜ ÛÂLTµ4 ‹ LTC4 (12).

™Ù· ÎÔÎÎÈÔ·ÙÙ·Ú· (ˈÛÈÓfiÊÈÏ·, ‚·ÛÂfiÊÈÏ·, ÛÈ-Ù¢ÙÈο ·ÙÙ·Ú·/Ì·ÛÙÔ·ÙÙ·Ú·), ÙÔ LT∞4 ÌÂÙ·ÙÚ¤-ÂÙ·È Û LTC4 ̤ۈ Ù˘ ÌÈÎÚÔÛˆÌȷ΋˜ Û˘ÓıÂÙ¿-Û˘ ÙÔ˘ LTC4 (∂ÈÎfiÓ· 1) Ì ۇ˙¢ÍË Ì ÁÏÔ˘Ù·ıÂÈ-fiÓË (13-15). ∆Ô LTC4 ÌÂٷʤÚÂÙ·È ÛÙÔÓ ÂÍˆÎ˘ÙÙ¿-ÚÈÔ ¯ÒÚÔ ‰È·Ì¤ÛÔ˘ ÂȉÈÎÔ‡ ÌÂÙ·ÊÔÚ¤·, fiÔ˘ ÌÂÙ·-‚ÔÏ›˙ÂÙ·È Ì¤Ûˆ Ù˘ Á-ÁÏÔ˘Ù·Ì˘ÏÙÚ·ÓÛÊÂÚ¿Û˘ ÛÂ

LTD4, ÙÔ ÔÔ›Ô Ì ÙË ÛÂÈÚ¿ ÙÔ˘ ‰È·Û¿Ù·È ·fi Â͈-΢ÙÙ¿ÚȘ ÂÙȉ¿Û˜ ÛÙÔ ‚ÚÔÁ¯ÔÛ˘Û·ÛÙÈÎfi ηȷÁÁÂÈÔ‰Ú·ÛÙÈÎfi LT∂4 (8). ™Ù· ÌÔÓÔ·ÙÙ·Ú·, Ì·ÎÚÔ-Ê¿Á· Î·È Ô˘‰ÂÙÂÚfiÊÈÏ·, ÙÔ LT∞4 ÌÂÙ·ÙÚ¤ÂÙ·È ÛÙÔ¯ËÌÂÈÔÙ·ÎÙÈÎfi ·Ú¿ÁÔÓÙ· LTµ4 ̤ۈ Ù˘ ˘‰ÚÔÏ¿-Û˘ ÙÔ˘ LT∞4, Û ·¿ÓÙËÛË ÔÈÎ›ÏˆÓ ÊÏÂÁÌÔÓˆ‰ÒÓÂÚÂıÈÛÌ¿ÙˆÓ (4,7,16-19). ∏ LTA4 ˘‰ÚÔÏ¿ÛË ·Â-ÓÂÚÁÔÔÈÂ›Ù·È ·fi ÙËÓ ÔÌÔÈÔÔÏÈ΋ ÚfiÛ‰ÂÛË ÙÔ˘LT∞4. ∏ Û‡ÓıÂÛË ÙˆÓ L∆s ¢ԉÒÓÂÙ·È fiÙ·Ó ÌfiÚÈ·ÛËÌ·ÙÔ‰fiÙËÛ˘, fiˆ˜ IL-1, TNF·, PAF, ‰ÈÂÁ›ÚÔ˘ÓÙËÓ ·ÂÏ¢ı¤ÚˆÛË ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ ÔͤԘ, Ú˘ıÌ›-˙Ô˘Ó ÚÔ˜ Ù· ¿Óˆ ÙËÓ 5-LO ‹ ¿ÁÔ˘Ó ÙËÓ ¤ÎÊÚ·-ÛË ÙÔ˘ FLAP (20).

∂›Ó·È ¯·Ú·ÎÙËÚÈÛÙÈÎfi fiÙÈ ÌfiÓÔ ÔÚÈṲ̂ӷ ·ÙÙ·-Ú· ·fi Ù· ÔÔ›· ·ÂÏ¢ıÂÚÒÓÔÓÙ·È Ù· LTs, ‰È·ı¤-ÙÔ˘Ó Ì˯·ÓÈÛÌfi ÁÈ· ÙËÓ de novo ‚ÈÔÛ‡ÓıÂÛ‹ ÙÔ˘˜,ÂÓÒ ÛÙ· ˘fiÏÔÈ· Ë ·Ú·ÁˆÁ‹ ÙÔ˘˜ Ú·ÁÌ·ÙÔÔÈ-Â›Ù·È Ì ‰È·Î˘ÙÙ¿ÚÈÔ ÌÂÙ·‚ÔÏÈÛÌfi ˘fi Ê˘ÛÈÔÏÔÁÈ-Τ˜ Î·È ·ıÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ (6,21,22). ™ÙȘ Â-ÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ, Ù· ÔÈÔÙÈο Î·È ÔÛÔÙÈο¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ Û¯ËÌ·ÙÈ˙fiÌÂÓˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓÂÍ·ÚÙÒÓÙ·È ·fi ÙËÓ ÈηÓfiÙËÙ· ÙˆÓ Ô˘‰ÂÙÂÚfiÊÈψÓÓ· ÚÔÌËıÂ‡Ô˘Ó LT∞4 ÛÙ· ·Ú·Î›ÌÂÓ· ·ÙÙ·Ú·,ÛÙ· ÔÔ›· ‰ÂÓ ·ÓȯÓ‡ÂÙ·È ‰Ú·ÛÙËÚÈfiÙËÙ· Ù˘ 5-LO(20). °È· ·Ú¿‰ÂÈÁÌ·, Ù· ÂÚ˘ıÚÔ·ÙÙ·Ú· ‰È·ı¤ÙÔ˘Ó˘‰ÚÔÏ¿ÛË, ÂÓÒ Ù· ·ÈÌÔÂÙ¿ÏÈ· (17) Î·È Ù· ÂÓ‰ÔıË-Ïȷο ·ÙÙ·Ú· (21) Û˘Óı¤ÙÔ˘Ó LTC4 Î·È LTB4 ·fiÙÔ LT∞4 Ô˘ ·ÂÏ¢ıÂÚÒÓÂÙ·È ·fi Ù· ·Ú·Î›ÌÂÓ·Ô˘‰ÂÙÂÚfiÊÈÏ· (23).

∆· LTs ·Ô‰ÔÌÔ‡ÓÙ·È ÛÙÔ ‹·Ú Î·È Ù· ·Ú¿Áˆ-Á¿ ÙÔ˘˜ (·Ú¿ÁˆÁ· ˆ- Î·È ‚-ÔÍ›‰ˆÛ˘, Ù· ÔÔ›··ÓȯÓ‡ÔÓÙ·È ÛÙ· Ô‡Ú·) Â›Ó·È ‚ÈÔÏÔÁÈÎÒ˜ ‰Ú·ÛÙÈοÚÔ˚fiÓÙ· (24). ∆Ô LTB4 ηٷ‚ÔÏ›˙ÂÙ·È Ì ‰È¿ÊÔ-ÚÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ ·Ó¿ÏÔÁ· Ì ÙÔÓ Ù‡Ô ÙˆÓ Î˘ÙÙ¿-ÚˆÓ Î·È ÙˆÓ ÈÛÙÒÓ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ·Ú¿ÁÂÙ·È. ™Ù·ÎÔÎÎÈÔ·ÙÙ·Ú· Î·È ÙÔ ‹·Ú ηٷ‚ÔÏ›˙ÂÙ·È Ì ÌÈÎÚÔ-ÛˆÌȷ΋ ˆ-ÔÍ›‰ˆÛË Ì¤Ûˆ ÙˆÓ ˆ-˘‰ÚÔÍ˘Ï·ÛÒÓÙÔ˘ ΢ÙÔ¯ÚÒÌ·ÙÔ˜ ƒ-450, CYP4F3A Î·È CYP4F3B·ÓÙ›ÛÙÔȯ·, ÛÙÔ ‹·Ú Î·È ÙÔ˘˜ ÓÂÊÚÔ‡˜ Ì ÙË ‰Ú¿-ÛË Ù˘ 12-˘‰ÚÔ͢-‰Â¸‰ÚÔÁÂÓ¿Û˘ Î·È ÛÙ· Ì˘ÂÏÔÂÈ-‰‹ ·ÙÙ·Ú· Î·È Ù· Ë·ÙÔ·ÙÙ·Ú· Ì ˘ÂÚÔÍ˘Ûˆ-Ìȷ΋ ‚-ÔÍ›‰ˆÛË (19,20).

Àԉԯ›˜ Ï¢ÎÔÙÚÈÂÓ›ˆÓ ∏ ‰È·ÊÔÚÂÙÈ΋ ‚ÈÔÏÔÁÈ΋ ‰Ú¿ÛË ÙˆÓ ‰‡Ô ÔÌ¿-

‰ˆÓ ÙˆÓ LTs ‰ÈηÈÔÏÔÁ› Ï‹Úˆ˜ ÙËÓ ·ÏÏËÏ›‰Ú·-Û‹ ÙÔ˘˜ Ì ‰‡Ô ‰È·ÎÚÈÙ¤˜ ÔÌ¿‰Â˜ ˘Ô‰Ô¯¤ˆÓ. ™‡Ì-ʈӷ Ì ÙË ¢ÈÂıÓ‹ ŒÓˆÛË º·ÚÌ·ÎÔÏÔÁ›·˜(IUPHAR), ÔÈ ˘Ô‰Ô¯Â›˜ ÙˆÓ LTB4 Î·È cysLTs ¯·Ú·-ÎÙËÚ›˙ÔÓÙ·È ˆ˜ BLT Î·È cysLT, ·ÓÙ›ÛÙÔȯ·.

Àԉԯ›˜ ÙˆÓ cysLT ∆· cysLTs ‰ÚÔ˘Ó ÛÙȘ Ï›˜ Ì˘˚Τ˜ ›Ó˜ (§ªπ) ηÈ

ÌÂÙ·‚¿ÏÏÔ˘Ó ÙË ‰È·ÂÚ·ÙfiÙËÙ· ÙˆÓ ·ÁÁ›ˆÓ ηÈ

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ÙËÓ ÂÈıËÏȷ΋ ¤ÎÎÚÈÛË, ÂÓÒ Ë ¤ÎÊÚ·ÛË ÙˆÓ ˘Ô-‰Ô¯¤ˆÓ ÙÔ˘˜ ÛÙÔÓ Ó‡ÌÔÓ· ¤¯ÂÈ È‰È·›ÙÂÚË ÛËÌ·-Û›· ÏfiÁˆ Ù˘ Û˘ÌÌÂÙÔ¯‹˜ ÙÔ˘˜ ÛÙËÓ ·ıÔÊ˘ÛÈÔ-ÏÔÁ›· ÙÔ˘ ¿ÛıÌ·ÙÔ˜. ™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ·Ó·ÊÔ-Ú¤˜, Ë Î·ÙËÁÔÚÈÔÔ›ËÛË ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓcysLTs ‚·Û›˙ÂÙ·È ÛÙȘ Ê·ÚÌ·ÎÔÏÔÁÈΤ˜ ȉÈfiÙËÙÂ˜ÙˆÓ ·ÓÙ·ÁˆÓÈÛÙÒÓ, ÂÓÒ ‰ÂÓ ·ÔÎÏ›ÂÙ·È ÂÚ·ÈÙ¤ÚˆÂÙÂÚÔÁ¤ÓÂÈ·, Ë ÔÔ›· ·ÔÚÚ¤ÂÈ ·fi ÙË ‰È·ÊÔÚÂÙÈ΋ÈÛ¯‡ Î·È Û˘ÁÁ¤ÓÂÈ· ÙˆÓ ÂÓ‰ÔÁÂÓÒÓ ÚÔÛ‰ÂÌ¿ÙˆÓ,‰ËÏ·‰‹ ÙˆÓ ›‰ÈˆÓ ÙˆÓ LTs, ·ÏÏ¿ Î·È ·fi ÙËÓ Î·Ù·-ÓÔÌ‹ ÙÔ˘˜ ÛÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÈÛÙÔ‡˜ ‰È·ÊfiÚˆÓ ÂÈ-‰ÒÓ (25). ª¤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó ¯·Ú·ÎÙËÚÈÛÙ› ‰‡ÔηÙËÁÔڛ˜ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ cysLTs, Ô˘ ·Ó‹ÎÔ˘ÓÛÙÔ˘˜ “˘Ô‰Ô¯Â›˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ڈÙ½Ó˜ G(GPCR) Î·È Ê¤ÚÔ˘Ó ÂÙ¿ ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ ÂÚÈÔ¯¤˜(7TM)”. ∞˘ÙÔ› Â›Ó·È ÔÈ cysLT1 Î·È cysLT2 (¶›Ó·Î·˜1), ÂÓÒ Ì ‚¿ÛË ÙË ÌË ·ÓÙ·fiÎÚÈÛË Û ÁÓˆÛÙÔ‡˜

·ÓÙ·ÁˆÓÈÛÙ¤˜ ¤¯ÂÈ ÚÔÙ·ı› Î·È Ì›· ÙÚ›ÙË, ÔÈcysLT3, ÔÈ ÔÔ›ÔÈ ÂÓÙÔ›˙ÔÓÙ·È ÛÙÔ ·Ú¤Á¯˘Ì·Ó¢ÌfiÓˆÓ ·ÓıÚÒˆÓ Î·È ÈÓ‰ÈÎÒÓ ¯ÔÈÚȉ›ˆÓ (26).

Àԉԯ›˜ ÙÔ˘ LTB4∆Ô LTB4 ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ¿Ì˘Ó· ÙÔ˘

ÍÂÓÈÛÙ‹, ‰ÈÂÁ›ÚÔÓÙ·˜ ÙËÓ ·ÂÏ¢ı¤ÚˆÛË Ï˘ÔÛˆ-ÌÈ·ÎÒÓ ÂÓ˙‡ÌˆÓ Î·È ÂÓÂÚÁÒÓ ·Ú·ÁÒÁˆÓ Ô͢Áfi-ÓÔ˘ (ROS, reactive oxygen species) ·fi Ù· ÎÔÎÎÈÔ-·ÙÙ·Ú· Î·È Ù· Ì·ÎÚÔÊ¿Á· (16,23,27). ¶ÚfiÎÂÈÙ·ÈÁÈ· ÙÔ Î‡ÚÈÔ ÚÔ˚fiÓ ÙˆÓ Ô˘‰ÂÙÂÚfiÊÈÏˆÓ Î·È Ì·ÎÚÔ-Ê¿ÁˆÓ Î·È ‰È·ı¤ÙÂÈ ÙËÓ ÈηÓfiÙËÙ· ·Ó¿ÎÙËÛ˘ ηÈÂÓÂÚÁÔÔ›ËÛ˘ ¢ڤˆ˜ Ê¿ÛÌ·ÙÔ˜ ·ÓÔÛÔÏÔÁÈÎÒÓÌÂÛÔÏ·‚ËÙÒÓ (20). ¶ÂÚÈÁÚ¿ÊÂÙ·È ˆ˜ ÈÛ¯˘Úfi˜ ¯Ë-ÌÂÈÔÙ·ÎÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜, Ô ÔÔ›Ô˜ Û˘ÌÌÂÙ¤¯ÂÈÛÙËÓ ¤Ó·ÚÍË, ÙÔ Û˘ÓÙÔÓÈÛÌfi Î·È ÙËÓ ÂÓ›Û¯˘ÛË Ù˘ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·¿ÓÙËÛ˘, ηÙ¢ı‡ÓÔÓÙ·˜ ÙËÓ Î›-ÓËÛË Î·È ÌÂÙ·Ó¿ÛÙ¢ÛË Î˘Ú›ˆ˜ ÙˆÓ Ô˘‰ÂÙÂÚfiÊÈ-ψÓ, ̤ۈ ‰‡Ô ÂÈÊ·ÓÂÈ·ÎÒÓ ˘Ô‰Ô¯¤ˆÓ (¶›Ó·Î·˜

HˆÛÈÓfiÊÈÏÔ§ÂÌÊÔ·ÙÙ·ÚÔ

KÔÚÙÈÎÔÛÙÂÚÔÂȉ‹

AÓ·ÛÙÔÏ›˜ FLAP

AÓ·ÛÙÔÏ›˜ 5-LOX

AÓ·ÛÙÔÏ›˜ ˘‰ÚÔÏ¿Û˘

LTA4 ˘‰ÚÔÏ¿ÛË

LTA4

LTA4

LTB4

LTB4

LTB4

LTB4

LTB4

LTC4

LTC4

LTC4

LTF4 LTE4

Glu

Glu

Gly

LTD4

GSH

FLAP

cPLA2

PL

cPLA2

Ca2+

Ca2+ TH2 ΢ÙÔΛÓ˜IgE

º¿Ú̷ηCa2+

Ca2+Ca2+

Ca2+

AA

¶˘Ú‹Ó·˜

LTC4

LTC4 Û˘ÓıÂÙ¿ÛË

5-LOX 5-LOX

Á-ÁÏÔ˘Ù·Ì˘ÏÙÚ·ÓÛÊÂÚ¿ÛË

·ÓÙ·ÁˆÓÈÛÙ¤˜ ˘Ô‰Ô¯¤ˆÓ BLT

CysLT 1

‰ÈÂÙȉ¿ÛË

T

EÚ

˘ıÚÔ·ÙÙ·

ÚÔ

EÓ‰ÔıËÏÈ·

Îfi ·ÙÙ·Ú

ÔA

∂ÈÎfiÓ· 1. ™‡ÓıÂÛË, ‰È·Î˘ÙÙ¿ÚÈÔ˜ ÌÂÙ·‚ÔÏÈÛÌfi˜ Î·È ÙÚÔÔÔÈËÙ¤˜ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ (LT). ∆Ô ·Ú·¯È‰ÔÓÈÎfi Ô͇ (∞∞) ·ÂÏ¢-ıÂÚÒÓÂÙ·È ·fi Ù· ÌÂÌ‚·ÓÈο ʈÛÊÔÏÈ›‰È· (PL) ̤ۈ Ù˘ ʈÛÊÔÏÈ¿Û˘ ∞2 (cPLA2) Î·È ÌÂÙ·ÙÚ¤ÂÙ·È Û LT∞4 ·fi ÙËÓ 5-ÏÈ-Ô͢ÁÂÓ¿ÛË (5-LO) ̤ۈ Ù˘ ÚˆÙ½Ó˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘ (FLAP). ™Ù· ˈÛÈÓfiÊÈÏ·, ‚·ÛÂfiÊÈÏ· Î·È ÛÈÙ¢-ÙÈο ·ÙÙ·Ú·, ÙÔ LT∞4 ÌÂÙ·ÙÚ¤ÂÙ·È Û LTC4 (___), ÙÔ ÔÔ›Ô ÌÂٷʤÚÂÙ·È ÛÙÔÓ ÂÍˆÎ˘ÙÙ¿ÚÈÔ ¯ÒÚÔ, fiÔ˘ ‰È·Û¿Ù·È Û LTD4 ηÈLT∂4. ™Ù· ÌÔÓÔ·ÙÙ·Ú·, Ù· Ì·ÎÚÔÊ¿Á· Î·È Ù· Ô˘‰ÂÙÂÚfiÊÈÏ·, ÙÔ LT∞4 ÌÂÙ·ÙÚ¤ÂÙ·È Û LTB4 (_._._). ∆· ÂÚ˘ıÚÔ·ÙÙ·Ú· Î·È Ù·∆-ÏÂÌÊÔ·ÙÙ·Ú· Û˘Óı¤ÙÔ˘Ó LTB4, ÂÓÒ Ù· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· Î·È Ù· ·ÈÌÔÂÙ¿ÏÈ· (∞) Û˘Óı¤ÙÔ˘Ó LTC4 Î·È LTB4 ·fi ÙÔ LT∞4Ô˘ ·ÂÏ¢ıÂÚÒÓÂÙ·È ·fi Ù· ·Ú·Î›ÌÂÓ· Ô˘‰ÂÙÂÚfiÊÈÏ· (....). (BLT: ˘Ô‰Ô¯¤·˜ LTB4, cysLT1: ˘Ô‰Ô¯¤·˜ ΢ÛÙÂ˚ÓÈÏÈÎÒÓ L∆s 1, Glu: ÁÏÔ˘Ù·ÌÈÎfi Ô͇, Gly: ÁÏ˘Î›ÓË, GSH: ÁÏÔ˘Ù·ıÂÈfiÓË, IgE:·ÓÔÛÔÛÊ·ÈÚ›ÓË ∂, ∆: ÌÂÙ·ÊÔÚ¤·˜ LTC4, TH2: ‚ÔËıËÙÈο ∆-ÏÂÌÊÔ·ÙÙ·Ú· 2).

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2), ÙÔÓ ˘„ËÏ‹˜ Û˘ÁÁ¤ÓÂÈ·˜ µLT1 (12) Î·È ÙÔÓ ¯·ÌË-Ï‹˜ Û˘ÁÁ¤ÓÂÈ·˜ µLT2 (28). OÈ ‰‡Ô ˘ÔÙ‡ÔÈ ·Ó‹-ÎÔ˘Ó ÛÙÔ˘˜ “˘Ô‰Ô¯Â›˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ڈ-Ù½Ó˜ G (GPCR) Î·È Ê¤ÚÔ˘Ó ÂÙ¿ ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ÂÚÈÔ¯¤˜ (7TM)”, ·ÏÏ¿ ‰È·ı¤ÙÔ˘Ó ÌÈÎÚ‹ ÔÌÔÏÔÁ›·Ì ¿ÏÏÔ˘˜ GPCR. ∆· ÁÔÓ›‰È¿ ÙÔ˘˜ Û¯ËÌ·Ù›˙Ô˘Ó Û˘-ÛÙ¿‰· (gene cluster) ÛÙÔ ÁÔÓȉ›ˆÌ· ÙÔ˘ ·ÓıÚÒÔ˘Î·È ÙÔ˘ ÔÓÙÈÎÔ‡, Ì ÛÙÂÓ¿ ·ÏÏËÏÔÂËÚ·˙fiÌÂÓˤÎÊÚ·ÛË (29,30). ∂›Ó·È ÂӉȷʤÚÔÓ fiÙÈ Ô ˘ÔÎÈÓË-Ù‹˜ ÙÔ˘ BLT1 ÂÓÙÔ›˙ÂÙ·È ÛÙÔ Ï·›ÛÈÔ ·Ó¿ÁÓˆÛ˘(ORF) ÙÔ˘ BLT2. ™‹ÌÂÚ·, ‰ÈÂÚÂ˘Ó¿Ù·È Ë ·ÈÙ›· Ô˘Ô‰‹ÁËÛ ÛÙÔ Û¯ËÌ·ÙÈÛÌfi Û˘ÛÙ¿‰ˆÓ ÁÔÓȉ›ˆÓ Ô˘Îˆ‰ÈÎÔÔÈÔ‡Ó ˘Ô‰Ô¯Â›˜ Ï¢ÎÔÙÚÈÂÓ›ˆÓ, ·ÏÏ¿ ηȿÏÏˆÓ ¯ËÌÂÈÔÂÏÎÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Î·Ù¿ ÙË ‰È·‰È-ηۛ· Ù˘ ÂͤÏÈ͢, ηıÒ˜ Î·È Ë ÁÂÓˆÌÈ΋ ÔÚÁ¿Óˆ-ÛË Ù˘ ÁÔÓȉȷ΋˜ ı¤Û˘ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ LTB4ÛÙÔ ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ 14 (19,31,32).

Œ¯ÂÈ, ›Û˘, ÂÚÈÁÚ·Ê› Ô ˘ÚËÓÈÎfi˜ ˘Ô‰Ô¯¤-·˜ PPAR· (peroxisome proliferator-activatedreceptor), ÛÙÔÓ ÔÔ›Ô ÚÔÛ‰¤ÓÂÙ·È ÙÔ LTB4 ηÈÂÓÂÚÁÔÔÈ› ÙË ÌÂÙ·ÁÚ·Ê‹ ÁÔÓȉ›ˆÓ Ô˘ Û˘ÌÌÂÙ¤-¯Ô˘Ó ÛÙË ÊÏÂÁÌÔÓÒ‰Ë ‰È·‰Èηۛ· (33).

º·ÚÌ·ÎÔÏÔÁÈΤ˜ ‰Ú¿ÛÂȘ ∆· ÌÂÙ·‚ÔÏÈο ÚÔ˚fiÓÙ· ÙÔ˘ ·Ú·¯È‰ÔÓÈÎÔ‡ Ôͤˆ˜,

ÚÔÛÙ·ÁÏ·Ó‰›Ó˜ Î·È Ï¢ÎÔÙÚȤÓÈ·, Â›Ó·È ÛËÌ·ÓÙÈÎÔ›ÌÂÛÔÏ·‚ËÙ¤˜ Ù˘ ÊÏÂÁÌÔÓ‹˜, Ì ڈٷÁˆÓÈÛÙÈÎfi Úfi-ÏÔ ÛÙË ÊÏÂÁÌÔÓÒ‰Ë ·¿ÓÙËÛË Ô˘ Û˘Óԉ‡ÂÈ ÙÔ¿ÛıÌ·, Ù· ·ÙÔÈο ÓÔÛ‹Ì·Ù· Î·È ÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈ-

ÛÙ‹ ηٿ ÙËÓ ÂÈÛ‚ÔÏ‹ Í¤ÓˆÓ ÚÔ˜ ÙÔÓ ÔÚÁ·ÓÈÛÌfi Ô˘-ÛÈÒÓ (8,25). ∏ ηٷÓÔÌ‹ ÙˆÓ ·Ó·‚ÔÏÈÎÒÓ ÂÓ˙‡ÌˆÓ Û‰ȿÊÔÚ· ·ÙÙ·Ú· ηıÈÛÙ¿ ÙË ‰È·Î˘ÙÙ¿ÚÈ· ÌÂÙ·ÊÔÚ¿ÙÔ˘˜ Ô˘ÛÈ·ÛÙÈ΋ Û fi,ÙÈ ·ÊÔÚ¿ ÛÙË ‚ÈÔÛ‡ÓıÂÛË Î·ÈÂÈÎÔÈÓˆÓ›· ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ (6,21,22).

∆· cysLTs, LTC4 Î·È LTD4 Â›Ó·È ‚ÚÔÁ¯ÔÛ˘Û·ÛÙÈ-ÎÔ› ·Ú¿ÁÔÓÙ˜, ÈÛ¯˘ÚfiÙÂÚÔÈ Ù˘ ÈÛÙ·Ì›Ó˘. ∆Ô LTE4,·Ó Î·È ÏÈÁfiÙÂÚÔ ÈÛ¯˘Úfi, ÂÓÔ¯ÔÔÈÂ›Ù·È Î·È ·˘Ùfi, fiˆ˜Î·È Ù· ˘fiÏÔÈ· cysLTs, ÁÈ· ÙËÓ ˘ÂÚ·ÓÙȉڷÛÙÈÎfi-ÙËÙ·, ÙËÓ ¤ÎÎÚÈÛË ‚ϤÓÓ˘ Î·È ÙËÓ ·fiÊÚ·ÍË ÙˆÓ ·Â-Ú·ÁˆÁÒÓ Û ·ÛıÌ·ÙÈÎÔ‡˜ ·ÛıÂÓ›˜ (8). ¶·Ú¿ÏÏËÏ·,Ù· cysLTs ÚÔ¿ÁÔ˘Ó ÙË ÌÂÙ·Ó¿ÛÙ¢ÛË ËˆÛÈÓÔʛψÓÛÙÔ˘˜ ·ÂÚ·ÁˆÁÔ‡˜ ·ÛıÌ·ÙÈÎÒÓ ·ÛıÂÓÒÓ.

∆· ·ÙÙ·Ú· Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙȘ ·ÓÙȉڿÛÂȘ˘ÂÚ¢·ÈÛıËÛ›·˜ Ù‡Ô˘ π ‰È·ı¤ÙÔ˘Ó Ì˯·ÓÈÛÌfiÛ‡ÓıÂÛ˘ Î·È ·ÂÏ¢ı¤ÚˆÛ˘ ÙˆÓ cysLTs. ™ÙÔ˘˜ÊÏÂÁÌ·›ÓÔÓÙ˜ ·ÛıÌ·ÙÈÎÔ‡˜ ·ÂÚ·ÁˆÁÔ‡˜, Û ·ÓÙ›-ıÂÛË Ì ÙÔÓ ÂÍ·ÎÚÈ‚ˆÌ¤ÓÔ ÚfiÏÔ ÙˆÓ ËˆÛÈÓÔʛψÓÓ· ·ÂÏ¢ıÂÚÒÓÔ˘Ó ÙÔÍÈΤ˜ ‚·ÛÈΤ˜ ÚˆÙ½Ó˜ ηÈLTC4 (14), Ô ÚfiÏÔ˜ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ‰ÂÓ Â›Ó·ÈηٷÓÔËÙfi˜, ·Ú’ fiÏÔ Ô˘ ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ˘˜ ·Â-Ú·ÁˆÁÔ‡˜ ·ÛıÂÓÒÓ Ì ¯ÚfiÓÈÔ ÛÔ‚·Úfi ¿ÛıÌ· (27).∆Ô LTB4 ÂËÚ¿˙ÂÈ ÙËÓ ÂÈÛÚÔ‹ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÌÂÙ¿·fi ÚfiÎÏËÛË Ì ·ÓÙÈÁfiÓ·, ·ÏÏ¿ Ë ÏÂÈÙÔ˘ÚÁÈ΋ ÛË-Ì·Û›· ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ ÛÙÔ ¿ÛıÌ· ·ÌÊÈÛ‚ËÙ›ٷÈ(34). ¶Ú¤ÂÈ, ¿ÓÙˆ˜, Ó· ÛËÌÂȈı› fiÙÈ Ù· ÁÔÓ›‰È·Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙÔ˘˜ ˘Ô‰Ô¯Â›˜ ÙÔ˘ LTB4 ÂÓÙÔ›-˙ÔÓÙ·È ÏËÛ›ÔÓ Ì›·˜ ·fi ÙȘ ÂÚÈÔ¯¤˜ ÙÔ˘ ÁÔÓȉÈÒ-Ì·ÙÔ˜ Ô˘ ¤¯Ô˘Ó Û˘Ó‰Âı› Ê·ÈÓÔÙ˘Èο Ì ÙÔ

¶›Ó·Î·˜ 1. ÷ڷÎÙËÚÈÛÙÈο ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ Î˘ÛÙÂ˚Ó˘ÏÈÎÒÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ (25,65-67)

CysLT1 CysLT2

™˘ÁÁ¤ÓÂÈ·: LTD4 > LTC4 > LTE4 ™˘ÁÁ¤ÓÂÈ·: LTC4 = LTD4>> LTE4∞ÓÙ·ÁˆÓÈÛÙ¤˜

BAYu9773 (ÌË ÂÎÏÂÎÙÈÎfi˜), MK571 BAYu9773 (ÌË ÂÎÏÂÎÙÈÎfi˜)CGP45715∞ (ÈÚ·ÏÔ˘Î¿ÛÙË), LY170680ICI204219 (˙·ÊÈÚÏÔ˘Î¿ÛÙË)MK476 (ÌÔÓÙÂÏÔ˘Î¿ÛÙË)ONO1078 (Ú·ÓÏÔ˘Î¿ÛÙË)Ro24-5913 (ÛÈÓ·ÏÔ˘Î¿ÛÙË), ZK3523SKF104353 (ÔÌÈÏÔ˘Î¿ÛÙË)

∫·Ù·ÓÔÌ‹ ÛÙÔÓ ¿Óıڈԧ›˜ Ì˘˚Τ˜ ›Ó˜ ·ÂÚ·ÁˆÁÒÓ, Ì·ÎÚÔÊ¿Á· Ó‡ÌÔÓ·, ∞ÓıÚÒÈÓ· ÂÚÈÊÂÚÈο Ï¢ÎÔ·ÙÙ·Ú·,ÂÚÈÊÂÚÈο ÌÔÓÔ·ÙÙ·Ú·, ˈÛÈÓfiÊÈÏ·, ÛÏ‹Ó·˜ ˈÛÈÓfiÊÈÏ·, Ó¢ÌÔÓÈ΋ ÊϤ‚·, ÛÏ‹Ó·˜,

ηډȿ, ÂÈÓÂÊÚ›‰È·, ∫¡™ªÔÚȷο ¯·Ú·ÎÙËÚÈÛÙÈο

°ÔÓ›‰ÈÔ: Ãq13-q21 °ÔÓ›‰ÈÔ: 13q14¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 338 ·ÌÈÓÔͤ· ¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 347 ·ÌÈÓÔͤ·28% ÔÌÔÏÔÁ›· Ì ÙÔÓ BLT1 38% ÔÌÔÏÔÁ›· Ì ÙÔÓ cysLT1ªÂÙ·‚›‚·ÛË ÙÔ˘ Û‹Ì·ÙÔ˜ ̤ۈ Gq/11, ·‡ÍËÛ˘ [Ca2+]i Î·È ÚˆÙÂ˚ÓÈ΋˜ ÎÈÓ¿Û˘ C

BLT1: ˘Ô‰Ô¯¤·˜ ÙÔ˘ Ï¢ÎÔÙÚÈÂÓ›Ô˘ LTB4, [Ca2+]i: ÂÓ‰Ô΢ÙÙ¿ÚÈ· Û˘ÁΤÓÙÚˆÛË ·Û‚ÂÛÙ›Ô˘ cysLT1: ˘Ô‰Ô¯¤·˜ ÙˆÓ Î˘ÛÙÂÓ˘ÏÈÎÒÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ-1 G: ÚˆÙ½ÓË G ∫¡™: ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ·

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¿ÛıÌ· (14q11.2-13) (35). ŒÙÛÈ, Ë ˘ÂÚ¤ÎÊÚ·ÛË ÙÔ˘LTB4 ÛÙË ÊÏÂÁÌÔÓ‹ (36-39) Î·È Ë ·Ú·Ù‹ÚËÛË fiÙÈ Ë¤ÏÏÂÈ„Ë Ï¢ÎÔÙÚÈÂÓ›ˆÓ Û ÔÓÙÈÎÔ‡˜ Ô‰ËÁ› Û ·ÓÂ-·Ú΋ ·¿ÓÙËÛË Û ÊÏÂÁÌÔÓÒ‰Ë ÂÚÂı›ÛÌ·Ù· (40)‰ÈηÈÔÏÔÁÔ‡Ó ÙËÓ ·Ó¿Ù˘ÍË ·ÓÙ·ÁˆÓÈÛÙÒÓ ÙˆÓ BLT˘Ô‰Ô¯¤ˆÓ ˆ˜ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ ·Ú·ÁfiÓÙˆÓ.∂›Û˘, Ë Ô˘‰ÂÙÂÚÔÊÈÏ›· Ô˘ ÂÈ̤ÓÂÈ ÌÂÙ¿ ·fi ¯Ô-Ú‹ÁËÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÔÊ›ÏÂÙ·È ÛÙËÓ ·Ó·-ÛÙÔÏ‹ Ù˘ ·fiÙˆÛ˘ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÏfiÁˆÙ˘ ·˘ÍË̤Ó˘ ÂÓ‰ÔÁÂÓÔ‡˜ Û‡ÓıÂÛ˘ ÙÔ˘ LTB4(27). ∏ ÂÎÏÂÎÙÈ΋ ·Ó·ÛÙÔÏ‹ Ù˘ Û‡ÓıÂÛ˘ ÙÔ˘ LTB4‹ Ô ·ÔÎÏÂÈÛÌfi˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ ÌÔÚ› Ó·ÚÔηϤÛÂÈ ·fiÙˆÛË ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ Î·È·Ó·ÛÙÔÏ‹ Ù˘ ‰Ú¿Û˘ ˘„ËÏÒÓ ‰fiÛÂˆÓ ÛÙÂÚÔÂȉÒÓ(27). ¶·Ú¿ÏÏËÏ·, Ë Û˘ÛÛÒÚ¢ÛË Î·È ÂÓÂÚÁÔÔ›ËÛËÙˆÓ Ô˘‰ÂÙÂÚÔʛψÓ, ηıÒ˜ Î·È Ë ·ÂÏ¢ı¤ÚˆÛËÙÔ˘ LTB4, ›Ûˆ˜ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘¯ÚfiÓÈ·˜ ·ÔÊÚ·ÎÙÈ΋˜ Ó¢ÌÔÓÔ¿ıÂÈ·˜, fiÔ˘ ËÙÔÈ΋ ÂÌÊ¿ÓÈÛË ÂÓfi˜ ¯ËÌÂÈÔÂÏÎÙÈÎÔ‡ Û‹Ì·ÙÔ˜ ÌÂ-ÛÔÏ·‚› ÛÙËÓ ÚÔÛÎfiÏÏËÛË Î˘ÎÏÔÊÔÚÔ‡ÓÙˆÓ Ô˘-‰ÂÙÂÚÔÊ›ÏˆÓ ÛÙÔ ÌÈÎÚÔ·ÁÁÂÈ·Îfi ÂÓ‰Ôı‹ÏÈÔ (41).

∏ ·ÓÔÛÔÏÔÁÈ΋ ‰Ú¿ÛË ÙÔ˘ LTB4 ÂÍ·ÚÙ¿Ù·È ·fiÙÔÓ Ù‡Ô ÙÔ˘ ΢ÙÙ¿ÚÔ˘ Ô˘ ÂÓÂÚÁÔÔÈ› (20). ™ÂÊ˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜, ÙÔ LTB4 ·Ú¿ÁÂÙ·È Î˘Ú›ˆ˜ÛÙ· Ô˘‰ÂÙÂÚfiÊÈÏ·, ÂÓÒ Î·Ù¿ ÙË ÊÏÂÁÌÔÓ‹ Û˘ÓÙ›ıÂ-Ù·È Î·È Û ¿ÏÏÔ˘˜ Ù‡Ô˘˜ ΢ÙÙ¿ÚˆÓ Ô˘ ‰È·ı¤ÙÔ˘Ó˘‰ÚÔÏ¿ÛË ÙÔ˘ LTA4 (22). ™Ù· ˈÛÈÓfiÊÈÏ· ÚÔ¿ÁÂÈÙË ¯ËÌÂÈÔÙ·Í›·, ÂÓÂÚÁÔÔÈ› ÙËÓ ÔÍÂȉ¿ÛË Ù˘NADPH Î·È ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ MAP ÎÈÓ·ÛÒÓ. ÀÂ-Ú¤ÎÊÚ·ÛË ÙÔ˘ LTB4 ¤¯ÂÈ ·Ó·ÊÂÚı› ÛÙËÓ „ˆÚ›·ÛË(36), ÙÔ ‚ÚÔÁ¯ÈÎfi ¿ÛıÌ· (37), ÙË ÚÂ˘Ì·ÙÔÂȉ‹ ·Ú-ıÚ›Ùȉ· (38), ÙËÓ ÂÏÎÒ‰Ë ÎÔÏ›Ùȉ· (39) Î·È ÙËÓ ÈÛ¯·È-

Ì›· (42). ∂›Û˘, Ë È‰ÈfiÙËÙ· ÙÔ˘ BLT1 ˆ˜ Û˘Ó˘Ô-‰Ô¯¤· ÁÈ· ÙÔÓ Èfi Ù˘ ›ÎÙËÙ˘ ·ÓÔÛÔ·Ó¿ÚÎÂÈ·˜∏πV-1 ‰ÂÓ ¤¯ÂÈ ·ÎfiÌË ÂȂ‚·Èˆı›, ·ÏÏ¿ ¤¯ÂÈ ˘Ô-ÛÙËÚȯı› fiÙÈ ·˘Ùfi˜ Èı·ÓÒ˜ Û˘ÌÌÂÙ¤¯ÂÈ ÛÙË ‰È·‰È-ηۛ· ÂÈÛfi‰Ô˘ ÙÔ˘ ÈÔ‡ ÛÙ· ·ÙÙ·Ú· (19,43).

∆¤ÏÔ˜, ·Ó Î·È ÙÔ ÂӉȷʤÚÔÓ ÁÈ· Ù· Ï¢ÎÔÙÚȤÓÈ·¤¯ÂÈ ÂÈÎÂÓÙÚˆı› ÛÙËÓ ÂÚÈʤÚÂÈ· ηÈ, Ì¿ÏÈÛÙ·,ÛÙÔ ÚfiÏÔ ÙÔ˘˜ ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· ÙˆÓ ·ÙÔÈÎÒÓÓÔÛËÌ¿ÙˆÓ, ÂÓÙÔ‡ÙÔȘ, ÙfiÛÔ Ë ·Ú·ÁˆÁ‹ ÙÔ˘˜ fiÛÔÎ·È Ë ·ÚÔ˘Û›· ÛÈÙ¢ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÛÙÔÓ ˘Ôı¿-Ï·ÌÔ, ·ÏÏ¿ Î·È Ô ¯·Ú·ÎÙËÚÈÛÌfi˜ Ù˘ ·Ó¿ÚÎÂÈ·˜Ù˘ Û‡ÓıÂÛ˘ ÙÔ˘ LTC4 ˆ˜ Ó¢ÚÔÌÂÙ·‚ÔÏÈ΋˜ Ófi-ÛÔ˘ (44), ·ÓÔ›ÁÔ˘Ó Ó¤Ô˘˜ ÔÚ›˙ÔÓÙ˜ ÁÈ· ÙË ÌÂϤÙËÙÔ˘ ‚ÈÔÏÔÁÈÎÔ‡ ÚfiÏÔ˘ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ.

°ÂÓˆÌÈ΋ - º·ÚÌ·ÎÔÁÂÓˆÌÈ΋∆Ô ¿ÛıÌ· Â›Ó·È ÔχÏÔÎÔ Û‡Ó‰ÚÔÌÔ, ÛÙÔ

ÔÔ›Ô ÁÂÓÂÙÈÎÔ› Î·È ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ηıÔÚ›˙Ô˘Ó ÙËÓ ·ÈÙÈÔÏÔÁÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ· Î·È ÙË Ê·È-ÓÔÙ˘È΋ ¤ÎÊÚ·ÛË (45). ™‹ÌÂÚ·, Û¯ÂÙÈο ÌÂÁ¿ÏÔ˜·ÚÈıÌfi˜ Ê·ÚÌ·ÎÔÁÂÓˆÌÈÎÒÓ ÌÂÏÂÙÒÓ ÂÛÙÈ¿˙ÂÈ ÛÙËÓÈı·Ó‹ Û˘ÌÌÂÙÔ¯‹ ÁÂÓÂÙÈÎÒÓ ÔÏ˘ÌÔÚÊÈÛÌÒÓ ÛÙË·ıÔÊ˘ÛÈÔÏÔÁ›· ÙÔ˘ ¿ÛıÌ·ÙÔ˜ (35). ∏ ÔÈÎÈÏfiÙËÙ·Ù˘ ·¿ÓÙËÛ˘ ÛÙ· ·ÓÙÈ·ÛıÌ·ÙÈο Ê¿Ú̷η Û˘Ì-‚¿ÏÏÂÈ ÛÙËÓ ÔÏ˘ÏÔÎfiÙËÙ· Ù˘ Ê·Ú̷΢ÙÈ΋˜·ÓÙÈÌÂÙÒÈÛ˘ Ù˘ ÓfiÛÔ˘, ·ÊÔ‡ ÌÂÁ¿ÏÔ ÔÛÔÛÙfiÙ˘ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ‰È·ÊfiÚˆÓ ·Ú·Ì¤ÙÚˆÓ ÔÊ›-ÏÂÙ·È ÛÙË ÁÂÓÂÙÈ΋ ÔÈÎÈÏfiÙËÙ· Î·È ÙÔÓ ÔÏ˘ÌÔÚÊÈ-ÛÌfi ÙˆÓ ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙȘ ÚˆÙ½Ó˜-ÛÙfi¯Ô˘˜ ÙˆÓ Ê·Ú̿ΈÓ, fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· Ô‚2-·‰ÚÂÓÂÚÁÈÎfi˜ ˘Ô‰Ô¯¤·˜ Î·È Ë 5-LO (46,47).∂·ÁˆÁ‹ Ù˘ ¤ÎÊÚ·Û˘ Ù˘ Û˘ÓıÂÙ¿Û˘ ÙÔ˘ LTC4

¶›Ó·Î·˜ 2. ÷ڷÎÙËÚÈÛÙÈο ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ LTB4 (12,19,28,30,32,68,69)

µLT1 µLT2

∞ÓÙ·ÁˆÓÈÛÙ¤˜CP105696, U75302, CP195543, O¡O4057 LY255283, ZK158252, O¡O4057

∫·Ù·ÓÔÌ‹∫˘Ú›ˆ˜ ÂÚÈÊÂÚÈο Ï¢ÎÔ·ÙÙ·Ú· Î·È ∂˘Ú›· ¤ÎÊÚ·ÛË Î˘Ú›ˆ˜ ÛÙÔ ÛÏ‹Ó·ÂÚÈÙÔÓ·˚ο Ì·ÎÚÔÊ¿Á·, ¯·ÌËÏ‹ ¤ÎÊÚ·ÛË ◊·Ú, ˆÔı‹ÎË, Ï¢ÎÔ·ÙÙ·Ú·, ηډȿ, ÓÂÊÚÔ›,ÛÙÔ ı‡ÌÔ Î·È ÛÏ‹Ó· Ï·ÎÔ‡ÓÙ·˜, ÂÁΤʷÏÔ˜

ªÔÚȷο ¯·Ú·ÎÙËÚÈÛÙÈο°ÔÓ›‰ÈÔ: 14q11.2-q12 °ÔÓ›‰ÈÔ ·ÓÔ‰Èο ÙÔ˘ BLT1¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 352 ·ÌÈÓÔͤ· ¶ÚˆÙ½ÓË ·ÔÙÂÏÔ‡ÌÂÓË ·fi 358 ·ÌÈÓÔͤ·∂ÓÂÚÁÔÔ›ËÛË Gi Î·È G16, ·Ó·ÛÙÔÏ‹ ·‰ÂÓ˘ÏÔ΢ÎÏ¿Û˘, ∂ÓÂÚÁÔÔ›ËÛË Gi, Gz, Gq, ·‡ÍËÛË πƒ3, ·Ó·ÛÙÔÏ‹ ÂÓÂÚÁÔÔ›ËÛË ÊˆÛÊÔÏÈ¿Û˘ C, ÎÈÓËÙÔÔ›ËÛË Ca2+i ·‰ÂÓ˘ÏÔ΢ÎÏ¿Û˘28% ÔÌÔÏÔÁ›· Ì ÙÔÓ cysLT1 39-45% ÔÌÔÏÔÁ›· Ì ÙÔÓ BLT1ƒ‡ıÌÈÛË ÌÂÙ·ÁÚ·Ê‹˜ ÂÍ·ÚÙÒÌÂÓË ·fi ÙÔÓ ÈÛÙfi 77% ÔÌÔÏÔÁ›· Ì ÙÔÓ CXCR1 ˘Ô‰Ô¯¤· Ù˘ IL-8(·ÁˆÁ‹ Û ̷ÎÚÔÊ¿Á·, ˈÛÈÓfiÊÈÏ·)

BLT1: ˘Ô‰Ô¯¤·˜ ÙÔ˘ Ï¢ÎÔÙÚÈÂÓ›Ô˘ LTB4Ca2+i: ÂÓ‰Ô΢ÙÙ¿ÚÈÔ ·Û‚¤ÛÙÈÔ cysLT1: ˘Ô‰Ô¯¤·˜ ÙˆÓ Î˘ÛÙÂÓ˘ÏÈÎÒÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ-1 G: ÚˆÙ½ÓË G IL-8: ÈÓÙÂÚÏ¢ΛÓË-8 πƒ3: ÙÚÈʈÛÊÔÚÈ΋ ÈÓÔÛÈÙfiÏË

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¤¯ÂÈ ·Ú·ÙËÚËı› Û Ó‡ÌÔÓ· ·ÙfiÌˆÓ Ì ¢·ÈÛıË-Û›· ÛÙËÓ ·ÛÈÚ›ÓË, ÂÓÒ Ë ·¿ÓÙËÛË ÛÙË ˙ÈÏ¢ÙfiÓˤ¯ÂÈ Û˘Û¯ÂÙÈÛÙ› Ì ÙÔÓ ÂÓÙÔÈÛÌfi ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔÁÔÓ›‰ÈÔ Ù˘ 5-LO (46,48). ∏ 5-LO ¤¯ÂÈ È‰È·›ÙÂÚË ÛË-Ì·Û›· ÛÙË Û‡ÓıÂÛË ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ Û ‰È¿ÊÔڷ·ÙÙ·Ú· Ô˘ ÂÌϤÎÔÓÙ·È ÛÙË ÊÏÂÁÌÔÓ‹, fiˆ˜ ٷˈÛÈÓfiÊÈÏ· Î·È Ù· ÛÈÙ¢ÙÈο ·ÙÙ·Ú· Î·È Ë Ú‡ıÌÈÛËÙÔ˘ ÂÓ˙‡ÌÔ˘ ÙfiÛÔ ÛÂ Â›Â‰Ô ‰Ú·ÛÙËÚÈfiÙËÙ·˜, fiÛÔÎ·È ÌÂÙ·ÁÚ·Ê‹˜ Î·È ÌÂÙ¿ÊÚ·Û˘ ÙÔ˘ ÁÔÓȉ›Ô˘ Ê·›-ÓÂÙ·È fiÙÈ ÂÍ·ÚÙ¿Ù·È ·fi ÙȘ ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ˘ÔÎÈ-ÓËÙ‹ ÙÔ˘ ÁÔÓȉ›Ô˘ (10). ∂›Û˘, ÙÔ ÁÔÓ›‰ÈÔ Ô˘ Έ-‰ÈÎÔÔÈ› ÙË Û˘ÓıÂÙ¿ÛË ÙÔ˘ LTC4 ÂÓÙÔ›˙ÂÙ·È ÛÙÔ5q35 Î·È Û˘Ó‰¤ÂÙ·È ÁÂÓÂÙÈο Ì ̛· ÂÚÈÔ¯‹ ÙÔ˘¯ÚˆÌÔÛÒÌ·ÙÔ˜ 5 Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔÓ ·ÙÔÈÎfi ηȷÛıÌ·ÙÈÎfi Ê·ÈÓfiÙ˘Ô (15). ¶·Ú¿ÏÏËÏ·, ‰È¿ÊÔÚÔÈÔÏ˘ÌÔÚÊÈÛÌÔ› Û ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ¤Ó˙˘-Ì· Û‡ÓıÂÛ˘ ÙˆÓ LTs ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛÙ› Ì ÙÔ Ê·È-ÓfiÙ˘Ô ÙÔ˘ ¿ÛıÌ·ÙÔ˜ ·fi ·ÛÈÚ›ÓË (49). ∏ Û‡Ó‰Â-ÛË ÙˆÓ ÔÏ˘ÌÔÚÊÈÛÌÒÓ ÛÙÔ ÁÔÓ›‰ÈÔ ÙÔ˘ cysLT2˘Ô‰Ô¯¤· Ì ÙÔ Ê·ÈÓfiÙ˘Ô ÙÔ˘ ¿ÛıÌ·ÙÔ˜ ÌÂÏÂÙ¿-Ù·È ÂÂȉ‹ Ô ÏËÛȤÛÙÂÚÔ˜ ‰Â›ÎÙ˘ ÛÙÔ ÁÔÓ›‰ÈÔ ÙÔ˘cysLT2 ˘Ô‰Ô¯¤· Â›Ó·È Ô D13S153, Ô ÔÔ›Ô˜ ¤¯ÂÈÛ˘Û¯ÂÙÈÛÙ› Ì ÙËÓ ÂÌÊ¿ÓÈÛË ·ÙÔÈÎÔ‡ ¿ÛıÌ·ÙÔ˜Û ÏËı˘ÛÌÔ‡˜ Ù˘ ªÂÁ¿Ï˘ µÚÂÙ·Ó›·˜ (50) ηÈÙ˘ π·ˆÓ›·˜ (51).

º·ÚÌ·ÎÔÏÔÁÈο ‰Ú·ÛÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ∏ Ê·ÚÌ·ÎÔÏÔÁÈ΋ ·Ú¤Ì‚·ÛË ÛÙË ‰Ú¿ÛË ÙˆÓ

Ï¢ÎÔÙÚÈÂÓ›ˆÓ Â›Ó·È ıˆÚËÙÈο ‰˘Ó·Ù‹ ÙfiÛÔ Û ›-Â‰Ô ˘Ô‰Ô¯¤ˆÓ, fiÛÔ Î·È ÛÙË Û‡ÓıÂÛË ÙˆÓ ÌÂÛÔ-Ï·‚ËÙÒÓ. ∏ ÂÙÂÚÔÁ¤ÓÂÈ· ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ‰ÈηÈÔÏÔ-Á› ÂÓ Ì¤ÚÂÈ ÙËÓ ÏËıÒÚ· ÙˆÓ ·ÓÙ·ÁˆÓÈÛÙÒÓ Ô˘¤¯Ô˘Ó ·Ó·Ù˘¯ı›. ¶·Ú¿ ÙÔ Û¯ÂÙÈο ÌÂÁ¿ÏÔ ·ÚÈıÌfi,̤¯ÚÈ Û‹ÌÂÚ· ÌfiÓÔ ÔÚÈṲ̂ÓÔÈ ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙˆÓ˘Ô‰Ô¯¤ˆÓ ÙˆÓ cysLTs (˙·ÊÈÚÏÔ˘Î¿ÛÙË, ÌÔÓÙÂÏÔ˘-οÛÙË, Ú·ÓÏÔ˘Î¿ÛÙË) Î·È ·Ó·ÛÙÔÏ›˜ Ù˘ Û‡ÓıÂ-Û˘ ÙˆÓ LTs (˙ÈÏ¢ÙfiÓË), Û˘ÓÔÏÈο ·Ó·ÊÂÚfiÌÂÓÔȈ˜ ÙÚÔÔÔÈËÙ¤˜ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ, ¤¯Ô˘Ó ‚ÚÂÈÂÊ·ÚÌÔÁ‹ ÛÙËÓ ÎÏÈÓÈ΋. OÈ ÙÚÔÔÔÈËÙ¤˜ ÙˆÓ Ï¢-ÎÔÙÚÈÂÓ›ˆÓ Â›Ó·È Ë ÈÔ ÚfiÛÊ·Ù· ÂÈÛ·¯ı›۷ ηÙË-ÁÔÚ›· ÂÓ·ÏÏ·ÎÙÈ΋˜ ‹ ÂÈÎÔ˘ÚÈ΋˜ ıÂڷ¢ÙÈ΋˜ÚÔÛ¤ÁÁÈÛ˘ ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂÈ-‰ÒÓ, ÌÂÙ¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ ÛÙËÓ ÎÏÈÓÈ-΋ Ú¿ÍË ÛÙȘ ·Ú¯¤˜ Ù˘ ‰ÂηÂÙ›·˜ ÙÔ˘ 1970, ÛÙËÓ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ‹ÈÔ˘ Î·È Ì¤ÙÚÈÔ˘ ¯ÚfiÓÈÔ˘¿ÛıÌ·ÙÔ˜, ÙÔ˘ ¿ÛıÌ·ÙÔ˜ ÌÂÙ¿ ·fi ¿ÛÎËÛË, ÛÙËÓ¤ÎıÂÛË Û „˘¯Úfi ·¤Ú· ‹ ÙË ¯ÔÚ‹ÁËÛË ·ÛÈÚ›Ó˘(25,52-56). ∞ӷʤÚÂÙ·È fiÙÈ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ¿ÙÔ˘˜ ηχÙÂÈ ÙÔ ¿ÛıÌ· ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ·ÛÈ-Ú›Ó˘ (AIA, aspirin-induced asthma), ÙÔ ÔÔ›Ô ¯·Ú·-ÎÙËÚ›˙ÂÙ·È ·fi ÂÌÊ¿ÓÈÛË ‚ÚÔÁ¯fiÛ·ÛÌÔ˘ ÌÂÙ¿ ·fiÏ‹„Ë Û·ÏÈ΢ÏÈÎÒÓ Î·È ¿ÏÏˆÓ ÌË ÛÙÂÚÔÂȉÒÓ ·ÓÙÈ-ÊÏÂÁÌÔÓˆ‰ÒÓ ·Ú·ÁfiÓÙˆÓ (57). ªÂٷ͇ ¿ÏψÓ, Ë

¯ÚfiÓÈ· ÊÏÂÁÌÔÓ‹ ÛÙÔ ∞π∞ Û¯ÂÙ›˙ÂÙ·È Ì ٷ ·˘ÍË̤-Ó· ›‰· ˈÛÈÓÔÊ›ÏˆÓ Î·È Û˘ÓıÂÙ¿Û˘ ÙÔ˘ LTC4,Ô˘ ÂÚȤ¯ÂÙ·È Û ·˘Ù¿ Ù· ·ÙÙ·Ú· (15,57). ÕÙÔÌ·Â˘·›ÛıËÙ· ÛÙËÓ ·ÛÈÚ›ÓË ·ÚÔ˘ÛÈ¿˙Ô˘Ó È‰È·›ÙÂÚ··˘ÍË̤ÓË ·Ú·ÁˆÁ‹ cysLTs, Èı·ÓÒ˜ ÏfiÁˆ ·Ó·-ÛÙÔÏ‹˜ Ù˘ Ô‰Ô‡ Ù˘ ΢ÎÏÔ͢ÁÂÓ¿Û˘ Î·È Â·Îfi-ÏÔ˘ı˘ ¢fi‰ˆÛ˘ Ù˘ Ô‰Ô‡ Ù˘ LO, Ì ·ÔÙ¤ÏÂÛÌ·Ó· ‰È·Ù·Ú¿ÛÛÂÙ·È Ë ÈÛÔÚÚÔ›· ÌÂٷ͇ ·ÓÙÈÊÏÂÁÌÔ-Óˆ‰ÒÓ (PGE2) Î·È ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ (cysLTs) ÌÂ-ÛÔÏ·‚ËÙÒÓ (57).

º·ÚÌ·ÎÔÎÈÓËÙÈο, Ë ˙ÈÏ¢ÙfiÓË ·ÏÏËÏÂȉڿ ÌÂÙË ıÂÔÊ˘ÏÏ›ÓË Î·È ¿ÏÏ· Ê¿Ú̷η Ô˘ ÌÂÙ·‚ÔÏ›˙Ô-ÓÙ·È Ì¤Ûˆ ÙÔ˘ ΢ÙÔ¯ÚÒÌ·ÙÔ˜ ƒ450, ÂÓÒ ÙÔ ¤Ó˙˘ÌÔ·˘Ùfi ·Ó·ÛÙ¤ÏÏÂÙ·È ·fi ıÂڷ¢ÙÈΤ˜ ‰fiÛÂȘ ˙·-ÊÈÚÏÔ˘Î¿ÛÙ˘, ·ÏÏ¿ fi¯È ·fi ·˘Ù¤˜ Ù˘ ÌÔÓÙÂÏÔ˘-οÛÙ˘ (57).

º·ÚÌ·ÎÔÏÔÁÈο ‰Ú·ÛÙÈΤ˜ Ô˘Û›Â˜, ÔÈ Ôԛ˜·Ó·ÛÙ¤ÏÏÔ˘Ó ÙË Û‡ÓıÂÛË ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ ‹·ÓÙ·ÁˆÓ›˙ÔÓÙ·È ÙË ‰Ú¿ÛË ÙÔ˘˜ ÛÙÔ˘˜ ˘Ô‰Ô¯Â›˜,ı· ÌÔÚÔ‡Û·Ó Ó· Ù‡¯Ô˘Ó ÁÂÓÈÎfiÙÂÚ˘ ÂÊ·ÚÌÔÁ‹˜ÛÙË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ·ÙÔÈÎÒÓ ÓÔÛËÌ¿-ÙˆÓ, fiˆ˜ ÂÈÂÊ˘Î›Ùȉ· (58), ÚÈÓ›Ùȉ· (59) Î·È ‰ÂÚ-Ì·Ù›Ùȉ· (60,61). ¶ÚÔηٷÚÎÙÈΤ˜ ÎÏÈÓÈΤ˜ ÌÂϤÙÂ˜Ô˘ ·ÊÔÚÔ‡Ó ÛÙËÓ Âԯȷ΋ ·ÏÏÂÚÁÈ΋ ÚÈÓÔÂÈÂ-Ê˘Î›Ùȉ· ¤‰ÂÈÍ·Ó fiÙÈ Ë Û˘Á¯ÔÚ‹ÁËÛË ·ÓÙ·ÁˆÓÈÛÙÒÓÙˆÓ ∏1 Î·È cysLT1 ˘Ô‰Ô¯¤ˆÓ ‹Ù·Ó ·ÔÙÂÏÂÛÌ·ÙÈ-ÎfiÙÂÚË Ù˘ ÌÔÓoıÂڷ›·˜ (62).

∆¤ÏÔ˜, ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ó·ÊÔÚ¤˜ ˘ÔÛÙËÚ›˙Ô˘ÓÙËÓ Èı·Ó‹ ÂÈÛ·ÁˆÁ‹ ÛÙË ıÂڷ¢ÙÈ΋ ÓÂfiÙÂÚˆÓ Ô˘-ÛÈÒÓ Ô˘ ‰ÚÔ˘Ó Û ‰È¿ÊÔÚ˜ Ê¿ÛÂȘ Ù˘ Û‡ÓıÂÛË˜ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ, ·ÏÏ¿ Î·È ÛÙÔ˘˜ ̆ ԉԯ›˜ ÙÔ˘˜. ∏˘‰ÚÔÏ¿ÛË ÙÔ˘ LTA4 ·Ó·Ê¤ÚıËΠfiÙÈ ·Ó·ÛÙ¤ÏÏÂÙ·È·fi Ô˘Û›Â˜ fiˆ˜ Ë Î·ÙÔÚ›ÏË Î·È Ë ÌÂÛÙ·Ù›ÓË (18).ªÂ ‚¿ÛË ÙË Û¯¤ÛË ‰ÔÌ‹˜-‰Ú¿Û˘, Ë Û‡ÓıÂÛË ÂÎÏÂ-ÎÙÈÎÒÓ ·Ú·ÁÒÁˆÓ ¤‰ˆÛ ÙȘ Ô˘Û›Â˜ SC56938 ηÈSC57461∞, ÔÈ Ôԛ˜ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ÂÎÏÂÎÙÈΤ˜ ηȷfi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ‰Ú·ÛÙÈΤ˜ Û ÂÈÚ·Ì·ÙÈο ÚfiÙ˘-·, ·ÏÏ¿ ‰ÂÓ ¤¯Ô˘Ó ‚ÚÂÈ ·ÎfiÌË ÎÏÈÓÈ΋ ÂÊ·ÚÌÔÁ‹(18,63). ¶ÔÏϤ˜ Ê·ÚÌ·ÎÔÏÔÁÈο ‰Ú·ÛÙÈΤ˜ Ô˘Û›Â˜Ô˘ ·ÏÏËÏÂȉÚÔ‡Ó Ì ÙÔ˘˜ ˘Ô‰Ô¯Â›˜ ÙÔ˘ LTB4 ‚Ú›-ÛÎÔÓÙ·È, ›Û˘, Û ÂÈÚ·Ì·ÙÈÎfi ÛÙ¿‰ÈÔ. ªÂٷ͇ ·˘-ÙÒÓ, Ë ZK151657 ·ÔÙÂÏ› ·ÁˆÓÈÛÙ‹ ÙfiÛÔ ÙˆÓ ÂÈÊ·-ÓÂÈ·ÎÒÓ BLT ˘Ô‰Ô¯¤ˆÓ, fiÛÔ Î·È ÙÔ˘ PPAR· Î·È ËZK158252 ¤¯ÂÈ ·ÓÙ·ÁˆÓÈÛÙÈ΋ ‰Ú¿ÛË ¤Ó·ÓÙÈ ÙˆÓ ˘Ô-‰Ô¯¤ˆÓ Ù˘ ΢ÙÙ·ÚÔÏ·ÛÌ·ÙÈ΋˜ ÌÂÌ‚Ú¿Ó˘ ηȷÁˆÓÈÛÙÈ΋ ¤Ó·ÓÙÈ ÙˆÓ ˘ÚËÓÈÎÒÓ, ÂÓÒ Ô ·ÓÙ·ÁˆÓÈ-ÛÙ‹˜ ZK183838 ‰ÂÓ Ê·›ÓÂÙ·È Ó· ·ÏÏËÏÂȉڿ Ì ÙÔÓ˘ÚËÓÈÎfi PPAR· ˘Ô‰Ô¯¤· (64).

µÈ‚ÏÈÔÁÚ·Ê›· 1. Kellaway CH, Trethewie ER. The liberation of a slow-reacting

smooth muscle-stimulating substance in anaphylaxis. Q JExp Physiol Cogn Med Sci 1940;30:121-145.

2. Brocklehurst WE. The release of histamine and formation of

MARC-APR 03 14-05-03 14:49 ™ÂÏ›‰·160

¶·È‰È·ÙÚÈ΋ 2003;66:155-162 Paediatriki 2003;66:155-162

161

a slow-reacting substance (SRS-A) during anaphylacticshock. J Physiol 1960;151:416-435.

3. Murphy RC, Hammarstrom S, Samuelsson B. LeukotrieneC: a slow-reacting substance from murine mastocytomacells. Proc Natl Acad Sci USA 1979;76:4275-4279.

4. Borgeat P, Samuelsson B. Transformation of arachidonicacid by rabbit polymorphonuclear leukocytes. J Biol Chem1979;254:2643-2646.

5. Samuelsson B. Leukotrienes: mediators of immediatehypersensitivity reactions and inflammation. Science1983;220:568-575.

6. Sala A, Folco G. Neutrophils, endothelial cells, and cysteinylleukotrienes: a new approach to neutrophil-dependentinflammation? Biochem Biophys Res Commun2001;283:1003-1006.

7. Serhan CN, Haeggstrom JZ, Leslie CC. Lipid mediatornetworks in cell signaling: update and impact of cytokines.FASEB J 1996;10:1147-1158.

8. Sala A, Zarini S, Bolla M. Leukotrienes: lipid bioeffectors ofinflammatory reactions. Biochemistry 1998;63:84-92.

9. Hirabayashi T, Kume K, Hirose K, Yokomizo T, Iino M, Itoh Het al. Critical duration of intracellular Ca2+ response requiredfor continuous translocation and activation of cytosolicphospholipase A2. J Biol Chem 1999;274:5163-5169.

10. Silverman E, In KH, Yandava C, Drazen JM. Pharmaco-genetics of the 5-lipoxygenase pathway in asthma. Clin ExpAllergy 1998;28 (5 Suppl):164-170.

11. Silverman ES, Drazen JM. The biology of 5-lipoxygenase:function, structure, and regulatory mechanisms. Proc AssocAm Physicians 1999;111:525-536.

12. Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T. A G-protein-coupled receptor for leukotriene B4 that mediateschemotaxis. Nature 1997;387:620-624.

13. MacGlashan DW Jr, Schleimer RP, Peters SP, SchulmanES, Adams GK 3rd, Newball HH et al. Generation ofleukotrienes by purified human lung mast cells. J Clin Invest1982;70:747-751.

14. Weller PF, Lee CW, Foster DW, Corey EJ, Austen KF, LewisRA. Generation and metabolism of 5-lipoxygenase pathwayleukotrienes by human eosinophils: predominantproduction of leukotriene C4. Proc Natl Acad Sci1983;80:7626-7630.

15. Penrose JF, Austen KF. The biochemical, molecular, andgenomic aspects of leukotriene C4 synthase. Proc AssocAm Physicians 1999;111:537-546.

16. Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA,Serhan CN. Leukotrienes and lipoxins: structures,biosynthesis, and biological effects. Science1987;237:1171-1176.

17. Sala A, Testa T, Folco G. Leukotriene A4, and notleukotriene B4, is the main 5-lipoxygenase metabolitereleased by bovine leukocytes. FEBS Lett 1996;388:94-98.

18. Haeggstrom JZ. Structure, function and regulation ofleukotriene A4 hydrolase. Am J Respir Crit Care Med2000;161:S25-S31.

19. Yokomizo T, Izumi T, Shimizu T. Leukotriene B4:metabolism and signal transduction. Arch BiochemBiophys 2001;385:231-241.

20. Crooks SW, Stockley RA. Leukotriene B4. Int J Biochem CellBiol 1998;30:173-178.

21. Feinmark SJ, Cannon PJ. Endothelial cell leukotriene C4

synthesis results from intercellular transfer of leukotriene A4synthesized by polymorphonuclear leukocytes. J BiolChem 1986;261:16466-16472.

22. Sala A, Bolla M, Zarini S, Muller-Peddinghaus R, Folco G.Release of leukotriene A4 versus leukotriene B4 from humanpolymorphonuclear leukocytes. J Biol Chem 1996;271:17944-17948.

23. Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, SmithMJ. Leukotriene B, a potent chemokinetic and aggregatingsubstance released from polymorphonuclear leukocytes.Nature 1980;286:264-265.

24. Sala A, Armetti L, Piva A, Folco G. An improved assay forurinary LTE4. Prostaglandins 1994;47:281-292.

25. Nicosia S, Capra V, Rovati GE. Leukotrienes as mediatorsof asthma. Pulm Pharmacol Ther 2001;14:3-19.

26. Tudhope SR, Cuthbert NJ, Abram TS, Jennings MA, MaxeyRJ, Thompson AM et al. BAY u9773, a novel antagonist ofcysteinyl-leukotrienes with activity against two receptorsubtypes. Eur J Pharmacol 1994;264:317-323.

27. Sampson AP. The role of eosinophils and neutrophils ininflammation. Clin Exp Allergy 2000;30 (1 Suppl):22-27.

28. Yokomizo T, Kato K, Terawaki K, Izumi T, Shimizu T. Asecond leukotriene B4 receptor, BLT2. A new therapeutictarget in inflammation and immunological disorders. J ExpMed 2000;192:421-432.

29. Kato K, Yokomizo T, Izumi T, Shimizu T. Cell-specifictranscriptional regulation of human leukotriene B4 receptorgene. J Exp Med 2000;192:413-420.

30. Yokomizo T, Kato K, Hagiya H, Izumi T, Shimizu T.Hydroxyeicosanoids bind to and activate the low affinityleukotriene B4 receptor, BLT2. J Biol Chem 2001;276:12454-12459.

31. Nilsson NE, Tryselius Y, Owman C. Genomic organizationof the leukotriene B4 receptor locus of human chromosome14. Biochem Biophys Res Commun 2000;274:383-388.

32. Tryselius Y, Nilsson NE, Kotarsky K, Olde B, Owman C.Cloning and characterization of cDNA encoding a novelhuman leukotriene B4 receptor. Biochem Biophys ResCommun 2000;274:377-382.

33. Devchand PR, Keller H, Peters JM, Vazquez M, GonzalezFJ, Wahli W. The PPARalpha-leukotriene B4 pathway toinflammation control. Nature 1996;384:39-43.

34. Evans DJ, Barnes PJ, Spaethe SM, van Alstyne EL, MitchellMI, O’Connor BJ. Effect of a leukotriene B4 receptorantagonist, LY293111, on allergen induced responses inasthma. Thorax 1996;51:1178-1184.

35. Collaborative Study on the Genetics of Asthma (CSGA). Agenome-wide search for asthma susceptibility loci inethnically diverse populations. Nat Genet 1997;15:389-392.

36. Iversen L, Kragballe K, Ziboh VA. Significance ofleukotriene-A4 hydrolase in the pathogenesis of psoriasis.Skin Pharmacol 1997;10:169-177.

37. Turner CR, Breslow R, Conklyn MJ, Andresen CJ, PattersonDK, Lopez-Anaya A et al. In vitro and in vivo effects ofleukotriene B4 antagonism in a primate model of asthma. JClin Invest 1996;97:381-377.

38. Griffiths RJ, Pettipher ER, Koch K, Farrell CA, Breslow R,Conklyn MJ et al. Leukotriene B4 plays a critical role in theprogression of collagen-induced arthritis. Proc Natl AcadSci 1995;92:517-521.

39. Cole AT, Pilkington BJ, McLaughlan J, Smith C, Balsitis M,

MARC-APR 03 14-05-03 14:49 ™ÂÏ›‰·161

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162

Hawkey CJ. Mucosal factors inducing neutrophil movementin ulcerative colitis: the role of interleukin 8 and leukotrieneB4. Gut 1996;39:248-254.

40. Byrum RS, Goulet JL, Snouwaert JN, Griffiths RJ, Koller BH.Determination of the contribution of cysteinyl leukotrienesand leukotriene B4 in acute inflammatory responses using 5-lipoxygenase- and leukotriene A4 hydrolase-deficient mice.J Immunol 1999;163:6810-6819.

41. Williams TJ, Jose PJ. Neutrophils in chronic obstructivepulmonary disease. Novartis Found Symp 2001;234:136-141.

42. Noiri E, Yokomizo T, Nakao A, Izumi T, Fujita T, Kimura S etal. An in vivo approach showing the chemotactic activity ofleukotriene B4 in acute renal ischemic-reperfusion injury.Proc Natl Acad Sci 2000;97:823-828.

43. Owman C, Garzino-Demo A, Cocchi F, Popovic M, SabirshA, Gallo RC. The leukotriene B4 receptor functions as anovel type of coreceptor mediating entry of primary HIV-1isolates into CD4-positive cells. Proc Natl Acad Sci1998;95:9530-9534.

44. Mayatepek E. Leukotriene C4 synthesis deficiency: amember of a probably underdiagnosed new group ofneurometabolic diseases. Eur J Pediatr 2000;159:811-818.

45. Holgate ST. Genetic and environmental interaction in allergyand asthma. J Allergy Clin Immunol 1999;104:1139-1146.

46. In KH, Asano K, Beier D, Grobholz J, Finn PW, Silverman EKet al. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factorbinding and reporter gene transcription. J Clin Invest1997;99:1130-1137.

47. Drazen JM, Silverman EK, Lee TH. Heterogeneity oftherapeutic responses in asthma. Br Med Bull 2000;56:1054-1070.

48. Israel E, Fischer AR, Rosenberg MA, Lilly CM, Callery JC,Shapiro J et al. The pivotal role of 5-lipoxygenase productsin the reaction of aspirin-sensitive asthmatics to aspirin. AmRev Respir Dis 1993;148:1447-1451.

49. Van Sambeek R, Stevenson DD, Baldasaro M, Lam BK,Zhao J, Yoshida S et al. 5’ flanking region polymorphism ofthe gene encoding leukotriene C4 synthase does notcorrelate with the aspirin-intolerant asthma phenotype in theUnited States. J Allergy Clin Immunol 2000;106:72-76.

50. Cookson W. The alliance of genes and environment inasthma and allergy. Nature 1999;402 (6760 Suppl):B5-11.

51. Kimura K, Noguchi E, Shibasaki M, Arinami T, Yokouchi Y,Takeda K et al. Linkage and association of atopic asthma tomarkers on chromosome 13 in the Japanese population.Hum Mol Genet 1999;8:1487-1490.

52. Drazen JM. Pharmacology of leukotriene receptor antagonistsand 5-lipoxygenase inhibitors in the management of asthma.Pharmacotherapy 1997;17:S22-S30.

53. Sampson AP, Cowburn AS, Sladek K, Adamek L,Nizankowska E, Szczeklik A et al. Profound overexpressionof leukotriene C4 synthase in bronchial biopsies fromaspirin-intolerant asthmatic patients. Int Arch AllergyImmunol 1997;113:355-357.

54. Bisgaard H. Leukotriene modifiers in pediatric asthmamanagement. Pediatrics 2001;107:381-390.

55. Leff AR. Discovery of leukotrienes and development ofantileukotriene agents. Ann Allergy Asthma Immunol2001;86 (1 Suppl):4-8.

56. Leff AR. Regulation of leukotrienes in the management of

asthma: biology and clinical therapy. Annu Rev Med2001;52:1-14.

57. Babu KS, Salvi SS. Aspirin and asthma. Chest2000;118:1470-1476.

58. Tiligada E, Giannoulaki V, Tesseromatis C. Leukotrienereceptor-mediated effect of fluoxetine on histamine levels inthe rat conjunctiva [abstract]. N-S Arch Pharmacol2001;363:R84.

59. Parnes SM. The role of leukotriene inhibitors in allergicrhinitis and paranasal sinusitis. Expert Opin Pharmacother2002;3:33-38.

60. Carucci JA, Washenik K, Weinstein A, Shupack J, Cohen DE.The leukotriene antagonist zafirlukast as a therapeutic agentfor atopic dermatitis. Arch Dermatol 1998;134:785-786.

61. Zhu YI, Stiller MJ. Preview of potential therapeuticapplications of leukotriene B4 inhibitors in dermatology. SkinPharmacol Appl Skin Physiol 2000;13:235-245.

62. Meltzer EO, Malmstrom K, Lu S, Prenner BM, Wei LX,Weinstein SF et al. Concomitant montelukast and loratadineas treatment for seasonal allergic rhinitis: a randomized,placebo-controlled clinical trial. J Allergy Clin Immunol2000;105:917-922.

63. Kachur JF, Askonas LJ, Villani-Price D, Ghoreishi-Haack N,Won-Kim S, Liang CD et al. Pharmacological characteri-zation of SC-57461A (3-[methyl[3-[4 (phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl), a potent andselective inhibitor of leukotriene A4 hydrolase II: in vivostudies. J Pharmacol Exp Ther 2002;300:583-587.

64. Devchand PR, Hihi AK, Perroud M, Schleuning WD,Spiegelman BM, Wahli W. Chemical probes that differentiallymodulate peroxisome proliferator-activated receptor alphaand BLTR, nuclear and cell surface receptors for leukotrieneB4. J Biol Chem 1999;274:23341-23348.

65. Lynch KR, O’Neill GP, Liu Q, Im DS, Sawyer N, Metters KMet al. Characterization of the human cysteinyl leukotrieneCysLT1 receptor. Nature 1999;399:789-793.

66. Sarau HM, Ames RS, Chambers J, Ellis C, Elshourbagy N,Foley JJ et al. Identification, molecular cloning, expression,and characterization of a cysteinyl leukotriene receptor. MolPharmacol 1999;56:657-663.

67. Heise CE, O’Dowd BF, Figueroa DJ, Sawyer N, Nguyen T,Im DS et al. Characterization of the human cysteinylleukotriene 2 receptor. J Biol Chem 2000;275:30531-30536.

68. Kamohara M, Takasaki J, Matsumoto M, Saito T, Ohishi T,Ishii H et al. Molecular cloning and characterization ofanother leukotriene B4 receptor. J Biol Chem 2000;275:27000-27004.

69. Yokomizo T, Izumi T, Shimizu T. Co-expression of two LTB4receptors in human mononuclear cells. Life Sci2001;68:2207-2212.

∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-03-2002 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 04-10-2002

¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ∞ÈηÙÂÚ›ÓË ∆˘ÏÈÁ¿‰· ∂ÚÁ·ÛÙ‹ÚÈÔ º·ÚÌ·ÎÔÏÔÁ›·˜ π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ ª. ∞Û›·˜ 75, ∆.∫. 115 27, ∞ı‹Ó· E-mail: aityliga@med.uoa.gr

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163

∆Ô ÚfiÁÚ·ÌÌ· ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘ (™¶∂) ‰È·Ó‡ÂÈ ÙÔ ÙÚ›ÙÔ ¤ÙÔ˜ ÂÊ·ÚÌÔÁ‹˜ ÙÔ˘Î·È ÛËÌ·ÓÙÈÎfi˜ ·ÚÈıÌfi˜ ÈÛÙÔÔÈËÙÈÎÒÓ ™¶∂ ¤¯Ô˘Ó ·ÔÛÙ·Ï› ÛÙÔ˘˜ ‰ÈηÈÔ‡¯Ô˘˜ ¶·È‰›·ÙÚÔ˘˜, ÔÈ ÔÔ›ÔÈÛ˘ÁΤÓÙÚˆÛ·Ó Ù· ··ÈÙÔ‡ÌÂÓ· 50 ÌfiÚÈ· ™¶∂ ÁÈ· Ù· ¤ÙË 2000 Î·È 2001. ªÂ ÙËÓ Â˘Î·ÈÚ›· ·˘Ù‹ Û˘Á¯·›ÚÔ˘-Ì ÙÔ˘˜ ¶·È‰›·ÙÚÔ˘˜ ·˘ÙÔ‡˜, ÔÈ ÔÔ›ÔÈ fi¯È ÌfiÓÔ ·ÓÙÈÏ‹ÊıËÎ·Ó ÙË ÛËÌ·Û›· Ù˘ ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ-΋˜ ∂η›‰Â˘Û˘, ·ÏÏ¿ Î·È ÔÏÔÎÏ‹ÚˆÛ·Ó ÂÈÙ˘¯Ò˜ ÙËÓ ÚÔ‚ÏÂfiÌÂÓË ‰È·‰Èηۛ·.

Ÿˆ˜ ¤¯ÂÈ ·Ó·ÎÔÈÓˆı› (1,2), ÙÔ ÚfiÁÚ·ÌÌ· ™¶∂ ‚·Û›˙ÂÙ·È ÛÙȘ ÚԉȷÁڷʤ˜ Ù˘ Confederation ofEuropean Specialists in Pediatrics (CESP), fiˆ˜ ·˘Ù¤˜ ‰È·ÌÔÚÊÒıËÎ·Ó ·fi ÙËÓ Committee for ContinuingMedical Education in Pediatrics Î·È ‰ËÌÔÛȇıËÎ·Ó ÛÙÔ European Journal of Pediatrics (3).

ÀÂÓı˘Ì›˙ÂÙ·È fiÙÈ ÁÈ· ÙËÓ ·fiÎÙËÛË ÙÔ˘ ÈÛÙÔÔÈËÙÈÎÔ‡ ™¶∂ ··ÈÙÔ‡ÓÙ·È 50 ÌfiÚÈ· (credits) ·Ó¿ ¤ÙÔ˜ ‹150 ÌfiÚÈ· ÁÈ· 3 Û˘Ó¯fiÌÂÓ· ¯ÚfiÓÈ·. ™Â οı ̛· ÒÚ· ‰È‰·Ûηϛ·˜ ·ÓÙÈÛÙÔȯ› ¤Ó· ÌfiÚÈÔ ™¶∂. O ÌÂÁ·Ï‡-ÙÂÚÔ˜ ·ÚÈıÌfi˜ ÌÔÚ›ˆÓ ·Ó¿ Ë̤ڷ Ô˘ ÌÔÚ› Ó· ·Ó·ÁÓˆÚÈÛÙ›, ·Û¯¤Ùˆ˜ ÙˆÓ ˆÚÒÓ Ô˘ ‰È·ÚΛ ÔÔÈ·‰‹-ÔÙ ÂÈÛÙËÌÔÓÈ΋ ÂΉ‹ÏˆÛË (™˘Ó¤‰ÚÈÔ, ™ÂÌÈÓ¿ÚÈÔ, ∏ÌÂÚ›‰· Î.Ï.), Â›Ó·È 6. ∂›Û˘, ÔÈ ÂÈÛÙËÌÔÓÈΤ˜ ÂÎ-‰ËÏÒÛÂȘ ÙˆÓ ‰È·ÊfiÚˆÓ ·È‰È·ÙÚÈÎÒÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ ‰›ÓÔ˘Ó 1 ÌfiÚÈÔ ·Ó¿ ÒÚ· ‰È‰·Ûηϛ·˜ ÁÈ· ÙÔ˘˜ ¶·È-‰›·ÙÚÔ˘˜ Ù˘ Û˘ÁÎÂÎÚÈ̤Ó˘ ÂȉÈÎfiÙËÙ·˜, ·ÏÏ¿ 0,5 ÌfiÚÈÔ ÁÈ· ÙÔ˘˜ ÁÂÓÈÎÔ‡˜ ¶·È‰›·ÙÚÔ˘˜ ‹ ÙÔ˘˜ ¶·È‰›·-ÙÚÔ˘˜ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ.

OÈ ¶·È‰›·ÙÚÔÈ Ô˘ Û˘ÁÎÂÓÙÚÒÓÔ˘Ó 50 ‹ ÂÚÈÛÛfiÙÂÚ· ÌfiÚÈ· ™¶∂ ̤۷ Û ¤Ó· ËÌÂÚÔÏÔÁÈ·Îfi ¤ÙÔ˜ ‹ 150ÌfiÚÈ· ̤۷ Û 3 Û˘Ó¯fiÌÂÓ· ËÌÂÚÔÏÔÁȷο ¤ÙË ı· Ú¤ÂÈ Ó· ˘Ô‚¿ÏÔ˘Ó ‹ Ó· ·ÔÛÙ›ÏÔ˘Ó ÌÂ Û˘ÛÙË̤ÓË·ÔÛÙÔÏ‹ Ù· Û¯ÂÙÈο ÈÛÙÔÔÈËÙÈο ÛÙËÓ ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·, ÁÈ· ÙËÓ ∂ÈÙÚÔ‹ ™˘Ó¯È˙fiÌÂÓ˘¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘, ÒÛÙ ӷ ÂΉÔıÔ‡Ó Ù· ÈÛÙÔÔÈËÙÈο ™¶∂.

∞ÎÔÏÔ˘ı› ηٿÏÔÁÔ˜ ÙˆÓ ™˘Ó‰ڛˆÓ, ™ÂÌÈÓ·Ú›ˆÓ Î·È ∏ÌÂÚ›‰ˆÓ Ô˘ ¤¯Ô˘Ó ·Ó·ÁÓˆÚÈÛÙ› ̤¯ÚÈ Û‹ÌÂÚ··fi ÙËÓ ∂ÈÙÚÔ‹ ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘, fiˆ˜ ›Û˘ Î·È ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÌÔÚ›ˆÓÔ˘ ·ÓÙÈÛÙÔÈ¯Ô‡Ó Û οı ̛· ·fi ÙȘ ÂΉËÏÒÛÂȘ ·˘Ù¤˜.

¶·Ú·Î·ÏÔ‡ÓÙ·È ÔÈ ÔÚÁ·ÓˆÙ¤˜ ÙˆÓ ÂÁÎÂÎÚÈÌ¤ÓˆÓ ÂÈÛÙËÌÔÓÈÎÒÓ ÂΉËÏÒÛÂˆÓ Ó· ·Ó·ÁÚ¿ÊÔ˘Ó ÛÙ· È-ÛÙÔÔÈËÙÈο ·Ú·ÎÔÏÔ‡ıËÛ˘ ÙÔÓ ·ÚÈıÌfi ÌÔÚ›ˆÓ ™¶∂ Ô˘ ¯ÔÚËÁ› Ë ÂΉ‹ÏˆÛË, ÙËÓ ÔÔ›· ÔÚÁ·ÓÒÓÔ˘Ó.

1. ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·18 ÌfiÚÈ· ÙÔ ¶·ÓÂÏÏ‹ÓÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ1 ÌfiÚÈÔ ·Ó¿ ÒÚ· ÁÈ· ÔÔÈ·‰‹ÔÙ ¿ÏÏË ÂΉ‹ÏˆÛË Ù˘ ∂.¶.∂.

2. ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

3. µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛ˶·È‰Ô·ÏÏÂÚÁÈÔÏÔÁÈ΋ ∏ÌÂÚ›‰·: 6 ÌfiÚÈ· ¶·È‰Ô·ÏÏÂÚÁÈÔÏfiÁÔÈ Î·È ¶·È‰ÔÓ¢ÌÔÓÔÏfiÁÔÈ3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

4. ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·ÏÔӛ΢4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

5. µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·ÏÔӛ΢4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

6. °’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·ÏÔӛ΢4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

7. ¢’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·ÏÔӛ΢4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

8. ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ5 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

¶ÚfiÁÚ·ÌÌ· ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘ ˘fi ÙËÓ ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·

¶∞π¢π∞∆ƒπ∫∏ ∂¡∏ª∂ƒø™∏ PEDIATRIC NEWS

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5 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË12. ¡ÂÔÁÓÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·ÏÔӛ΢

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4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË14. ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›· µÔÚ›Ԣ ∂ÏÏ¿‰Ô˜

8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË2 ÌfiÚÈ· Ë ªËÓÈ·›· ∂Ή‹ÏˆÛ˺ÚÔÓÙÈÛÙ‹ÚÈÔ ∞Ó·˙ˆÔÁfiÓËÛ˘ ¡ÂÔÁÓÔ‡-µÚ¤ÊÔ˘˜-¶·È‰ÈÔ‡: 6 ÌfiÚÈ· ¡ÂÔÁÓÔÏfiÁÔÈ Î·È ∂ÓÙ·ÙÈÎÔÏfiÁÔÈ ¶·È‰›·ÙÚÔÈ3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ

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16. ∞ÈÌ·ÙÔÏÔÁÈ΋-OÁÎÔÏÔÁÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 8 ÌfiÚÈ· ¶·È‰Ô·ÈÌ·ÙÔÏfiÁÔÈ-¶·È‰ÔÔÁÎÔÏfiÁÔÈ4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

17. ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ∂ÊË‚È΋˜ π·ÙÚÈ΋˜∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 8 ÌfiÚÈ· ¶·È‰›·ÙÚÔÈ Ì¤ÏË Ù˘ ∂Ù·ÈÚ›·˜ ∂ÊË‚È΋˜ π·ÙÚÈ΋˜4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

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19. µ’ ¶·ıÔÏÔÁÈÎfi˜ ∆Ô̤·˜, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

20. ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 8 ÌfiÚÈ· ¶·È‰›·ÙÚÔÈ ∂ÓÙ·ÙÈ΋˜ ¡ÔÛËÏ›·˜4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

21. ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ "∞Á›· ™ÔÊ›·", ∞ı‹Ó·∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 8 ÌfiÚÈ· ¶·È‰›·ÙÚÔÈ ∂ÓÙ·ÙÈ΋˜ ¡ÔÛËÏ›·˜4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

22. µ’ ¡ÂÔÁÓÔÏÔÁÈÎfi ∆Ì‹Ì· ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

23. ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ¶·È‰È·ÙÚÈ΋˜ °·ÛÙÚÂÓÙÂÚÔÏÔÁ›·˜, ∏·ÙÔÏÔÁ›·˜ Î·È ¢È·ÙÚÔÊ‹˜∏ÌÂÚ›‰·: 6 ÌfiÚÈ· ¶·È‰ÔÁ·ÛÙÚÂÓÙÂÚÔÏfiÁÔÈ3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوә˘ÌfiÛÈÔ: 5 ÌfiÚÈ· ¶·È‰ÔÁ·ÛÙÚÂÓÙÂÚÔÏfiÁÔÈ3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

24. ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ∫ÔÈÓˆÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶ÚÔ·ÁˆÁ‹˜ Ù˘ ÀÁ›·˜∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 5 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

¶·È‰È·ÙÚÈ΋ 2003;66:163-165 Paediatriki 2003;66:163-165

164

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¶·Ú¿ÚÙËÌ· £ÂÛÛ·Ï›·˜: 4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

25. ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ¶·È‰È·ÙÚÈ΋˜ Î·È ∂ÊË‚È΋˜ ∂Ó‰ÔÎÚÈÓÔÏÔÁ›·˜∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 4 ÌfiÚÈ· ¶·È‰ÔÂÓ‰ÔÎÚÈÓÔÏfiÁÔÈ2 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

26. ∂ÏÏËÓÈ΋ ¶·È‰ÔÓ¢ÌÔÓÔÏÔÁÈ΋ ∂Ù·ÈÚ›· ÛÂ Û˘ÓÂÚÁ·Û›· ÌÂ:·) ∞ÏÏÂÚÁÈÔÏÔÁÈÎfi ∆Ì‹Ì· °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶ÂÓÙ¤Ï˘¶·È‰Ô·ÏÏÂÚÁÈÔÏÔÁÈ΋ ∏ÌÂÚ›‰·: 9 ÌfiÚÈ· ¶·È‰Ô·ÏÏÂÚÁÈÔÏfiÁÔÈ Î·È ¶·È‰ÔÓ¢ÌÔÓÔÏfiÁÔÈ5 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوӂ) ªÔÓ¿‰· ¶·È‰ÔÓ¢ÌÔÓÔÏÔÁ›·˜ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ∏ÌÂÚ›‰· ·Ó¿ ‰ÈÂÙ›·: ¶ÚÒÙÔ˜ ·ÎÏÔ˜: 3 ÌfiÚÈ· ÁÈ· ¶·È‰›·ÙÚÔ˘˜ Î·È ¶·È‰ÔÓ¢ÌÔÓÔÏfiÁÔ˘˜¢Â‡ÙÂÚÔ˜ ·ÎÏÔ˜: 3 ÌfiÚÈ· ÌfiÓÔ ÁÈ· ¶·È‰ÔÓ¢ÌÔÓÔÏfiÁÔ˘˜

27. ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· §ÔÈÌÒ͈Ó5 ÌfiÚÈ· ™ÂÌÈÓ¿ÚÈÔ

28. ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ¶ÂÚÈÁÂÓÓËÙÈ΋˜ π·ÙÚÈ΋˜8 ÌfiÚÈ· ¡ÂÔÁÓÔÏfiÁÔÈ4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔًوÓ

29. ∫·Ú·Ì·Ó‰¿ÓÂÈÔ ¡ÔÛÔÎÔÌÂ›Ô ¶·ÙÚÒÓ, ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋3 ÌfiÚÈ· ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË

∏ ∂ÈÙÚÔ‹ ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘, ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÙËÓ ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋∂Ù·ÈÚ›·, ı· ‰ËÌÔÛȇÂÈ ÙÔÓ Î·Ù¿ÏÔÁÔ ÙˆÓ ÂÁÎÂÎÚÈÌ¤ÓˆÓ ÚÔÁÚ·ÌÌ¿ÙˆÓ ™¶∂, ÒÛÙ ӷ Â›Ó·È ÚÔÛ·ÚÌÔ-Ṳ̂ÓÔ˜ ÛÙËÓ ÂοÛÙÔÙ ÂÈÎÚ·ÙÔ‡Û· ηٿÛÙ·ÛË.

O ¶Úfi‰ÚÔ˜ Ù˘ ∂ÏÏËÓÈ΋˜ O ¶Úfi‰ÚÔ˜ Ù˘ ∂ÈÙÚÔ‹˜¶·È‰È·ÙÚÈ΋˜ ∂Ù·ÈÚ›·˜ ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘

∞Ó‰Ú¤·˜ °. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜ ¡ÈÎfiÏ·Ô˜ °. ªÂÚ¿Ù˘

µÈ‚ÏÈÔÁÚ·Ê›· 1. ªÂÚ¿Ù˘ ¡°, ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜ ∞. ŒÓ·ÚÍË ÚÔÁÚ¿ÌÌ·ÙÔ˜ ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘ ˘fi ÙËÓ ∂ÏÏËÓÈ΋ ¶·È-

‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·. ¶·È‰È·ÙÚÈ΋ 1999;62:508-510.2. ªÂÚ¿Ù˘ ¡°, ª·Ï·Î¿-∑·ÊÂÈÚ›Ô˘ ∞. ¶ÚfiÁÚ·ÌÌ· ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘ ˘fi ÙËÓ ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·È-

Ú›·. ¶·È‰È·ÙÚÈ΋ 2001;64:633-635.3. D’ Apuzzo V, Helwig H, Siimes M. Charter on continuing medical education in paediatrics in the European Union. Eur J Pediatr

1998;157:192-193.

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∫‡ÚÈ ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÂ, ⁄ÛÙÂÚ· ·fi ÙȘ ‰È¢ÎÚÈÓÈÛÙÈΤ˜ Û·˜ ÂÈÛËÁ‹ÛÂȘ ÛÙË §¿ÚÈÛ· Î·È ÛÙËÓ ÂÙ‹ÛÈ· ıÂڷ¢ÙÈ΋ ÂÓË̤ڈÛË

Û¯ÂÙÈο Ì ÙÔ ÂÌ‚fiÏÈÔ Ù˘ ÔÏÈÔÌ˘ÂÏ›Ùȉ·˜, Ô Î¿ı ÂÓËÌÂڈ̤ÓÔ˜ ·È‰›·ÙÚÔ˜ ÁÓˆÚ›˙ÂÈ Ï¤ÔÓ ÙÔ ÚÔÙÂÈÓfi-ÌÂÓÔ Û¯‹Ì· ‹ Ì¿ÏÏÔÓ Ù· ÚÔÙÂÈÓfiÌÂÓ· Û¯‹Ì·Ù· ÁÈ· Ù· ÂÓۈ̷و̤ӷ Ì ¿ÏÏ· ÂÌ‚fiÏÈ· ÂÓ·›ÛÈÌ· ÂÌ‚fiÏÈ·ÔÏÈÔÌ˘ÂÏ›Ùȉ·˜ Î·È ÙȘ ÂÚÈÔÚÈṲ̂Ó˜ ϤÔÓ ÂӉ›ÍÂȘ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ Sabin. ∂ÓÙÔ‡ÙÔȘ, Ë ÂÙ·ÈÚ›· µπ∞¡∂•,Ë ÔÔ›· ÂÍ·ÎÔÏÔ˘ı› Ó· ÂÈÛ¿ÁÂÈ ÙÔ ÂÌ‚fiÏÈÔ Sabin Ì ‚Ú·¯‡ ¯ÚfiÓÔ ËÌÂÚÔÌËÓ›· Ï‹Í˘ ¤¯ÂÈ ÛËÌÂÈÒÛÂÈ Î·Ù’Â·Ó¿ÏË„ÈÓ ÂÏÏ›„ÂȘ, ÙȘ Ôԛ˜ Ù›ÓÂÈ Ó· Û˘ÌÏËÚÒÛÂÈ Ë ÂÙ·ÈÚ›· °ÂÚÔÏ˘Ì¿ÙÔ˘ Ì ÙÔ ÂÌ‚fiÏÈÔ POLY-ORAL. ∞ÚÎÂÙÔ› ÂÎ ÙˆÓ Û˘Ó·‰¤ÏÊˆÓ ÙÔ ¯ÚËÛÈÌÔÔÈÔ‡Ó, ·Ó Î·È ÙÔ Ï›ÛÙÔ ÙÔ ÂÌ‚ÔÏ›Ô˘ ·Ú·Ì¤ÓÂÈ ÚÔÛÚÔ-ÊË̤ÓÔ Â› ÙˆÓ ÙÔȯˆÌ¿ÙˆÓ ÙÔ˘ Ï·ÛÙÈÎÔ‡ ÊÈ·Ïȉ›Ô˘ ÌÂÙ¿ ·fi ÙËÓ ÂÎΤӈۋ ÙÔ˘, Ì ·ÔÙ¤ÏÂÛÌ· ÙÔ ÂÌ-‚ÔÏÈ·˙fiÌÂÓÔ ‚Ú¤ÊÔ˜ Ó· Ï·Ì‚¿ÓÂÈ ÙÂÏÈο ÌÈÎÚfi ÙÌ‹Ì· Ù˘ ‰fiÛˆ˜. ∂Âȉ‹ Ë ÔÏÈÔÌ˘ÂÏ›ÙȘ ·Ú·Ì¤ÓÂÈ ÛÙËÌÓ‹ÌË ÙˆÓ ÂÚÈÛÛfiÙÂÚˆÓ, ȉ›ˆ˜ ·Ï·ÈÒÓ ·È‰È¿ÙÚˆÓ, ˆ˜ Ì›· ÛÔ‚·Ú‹ ÓfiÛÔ˜, ı· ‹Ù·Ó ̷ο‚ÚÈÔ Ï¿ıÔ˜ ¿ÓÌÂÙ¿ ·fi ÙfiÛ· ÂÌ‚fiÏÈ· Ô˘ ‰È·ı¤ÙÔ˘Ì ۋÌÂÚ· Ì ÂÈfiÏ·È· Û˘ÌÂÚÈÊÔÚ¿ Î·È ¯ÂÈÚÈÛÌÔ‡˜, Û˘ÓÙÂϤÛÔ˘ÌÂÒÛÙ ӷ ·ÓÂÌÊ·ÓÈÛÙ› ÛÙË ¯ÒÚ· Ì·˜ Ë ÔÏÈÔÌ˘ÂÏ›Ùȉ·, ÙÒÚ· Ô˘ ÛÙË ¯ÒÚ· Ì·˜ ˘¿Ú¯ÂÈ ¤Ó·˜ ÈηÓfi˜ ·Îfi-ÌË ·ÚÈıÌfi˜ ·ÌfiÏÈ·ÛÙˆÓ ÙÛÈÁÁ¿ÓˆÓ Î·È ÌÂÙ·Ó·ÛÙÒÓ.

∫·ÙfiÈÓ ÙÔ‡ÙÔ˘, ÈÛÙ‡ˆ fiÙÈ Â›Ó·È ¯Ú‹ÛÈÌÔ Ó· ‰ËÌÔÛÈ¢Ù› Ë ·ÚÔ‡Û· ÂÈÛÙÔÏ‹ Î·È Ì›· ÂÓËÌÂÚˆÙÈ΋·¿ÓÙËÛË ÛÙÔ ÂÚÈÔ‰ÈÎfi Ì·˜.

µfiÏÔ˜, 18-02-2003 £Âfi‰ˆÚÔ˜ ¶ÂÚÚ¿Î˘

∫‡ÚÈ ¶ÂÚÚ¿ÎË, ™˘ÌʈÓÒ ·fiÏ˘Ù· Ì ÙȘ ·Ú·ÙËÚ‹ÛÂȘ Û·˜ ÁÈ· ÙÔ POLY-ORAL. Ÿˆ˜ ÁÓˆÚ›˙ÂÙÂ, ÙÔ ÂÌ‚fiÏÈÔ ·˘Ùfi ‰ÂÓ

¤¯ÂÈ ÂÁÎÚÈı› ·fi ÙÔÓ ∂Oº. ™Â ÂÚÈÙÒÛÂȘ, fï˜, ¤ÏÏÂȄ˘ ÙÔ˘ Sabin, Ë ÂÙ·ÈÚ›· ˘Ô‚¿ÏÏÂÈ ·›ÙËÛË ÛÙÔÓ∂Oº Ó· ÂÁÎÚÈı› Ë ÂÈÛ·ÁˆÁ‹ ÔÚÈÛÌ¤ÓˆÓ ÙÂÌ·¯›ˆÓ ÂÌ‚ÔÏ›ˆÓ ·fi ¿ÏϘ ¯ÒÚ˜ Ô˘ ¤¯ÂÈ ÂÁÎÚÈı› ÁÈ· ÙËÓ Î¿-Ï˘„Ë ÙˆÓ ·Ó·ÁÎÒÓ.

∏ χÛË ÛÙÔ Úfi‚ÏËÌ· Â›Ó·È Ó· ¯ÚËÛÈÌÔÔÈԇ̠fiÏÔÈ ÙÔ IPV.

O ¶Úfi‰ÚÔ˜ Ù˘ ∂.¶.∂. ∫·ı. ∞. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜

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166

∂¶π™∆O§∏ ¶ƒO™ ∆∏ ™À¡∆∞•∏ LETTER TO THE EDITOR

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