MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·133
¶·È‰È·ÙÚÈ΋ 2003;66:133-139
∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞
Paediatriki 2003;66:133-139
ORIGINAL ARTICLE
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 Crete H. 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
¶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‹ıËΠ·fi ÙË Û˘ÓÂÚÁ·Û›· È·ÙÚÒÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·È ÛÙËÓ ÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜ Û ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘ ∫Ú‹Ù˘ Ì ¤Ó· ÂÍÂȉÈÎÂ˘Ì¤ÓÔ ·ÓÂÈÛÙËÌÈ·Îfi ΤÓÙÚÔ. OÈ ÁÈ·ÙÚÔ› Ô˘ ÂÚÁ¿˙ÔÓÙ·È Û 8 ΤÓÙÚ· ˘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 ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô Û 17/112 ·ÛıÂÓ›˜ (15,2%) ÂȂ‚·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, ÂÓÒ ÛÙÔ˘˜ ›‰ÈÔ˘˜ Î·È ÙȘ ÔÈÎÔÁ¤ÓÂȤ˜ ÙÔ˘˜ ·Ú·Û¯¤ıËΠοı ‰˘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·‚ÔÏÈÎÒÓ 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 often underdiagnosed. The aim of this pilot study is to present the main outcomes and the experience gained as a result of the cooperation between the medical staff of the primary health care system in the rural areas of Crete and the tertiary care doctors at the referral University Hospital of Heraklion, Crete. Medical staff working in 8 primary health care centers in rural Crete (pediatricians and general practitioners) referred 112 patients suspected for metabolic disease who fulfilled at least 1 criterion (symptom or sign) from a pre-constructed questionnaire. After detailed clinical and laboratory investigations 17 of 112 patients (15.2 %) were found to have an inherited metabolic disease. Fourteen of these patients were children. Where possible, these patients were provided with the appropriate treatment. Additionally, socio-economical support and genetic consultation was made available to all of them and their families. A high index of suspicion, proper training and supply of information to the primary health care physicians may contribute to the timely detection of patients with inherited metabolic diseases and the prevention and treatment of new cases.
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 ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ, ∫Ú‹ÙË 6 University Hospital Nigmegen, The Netherlands Department of Neurology and Pediatrics
1 Department of Pediatrics, Medical School, University of Heraklion, Crete 2 Department of Neurology, Medical School, University of Heraklion, Crete 3 Department of Public Health and Social Medicine, Medical School, 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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Paediatriki 2003;66:133-139
ÂÓË̤ڈÛË ÌÔÚÔ‡Ó Ó· ·ÓȯÓÂ‡Ô˘Ó ¤ÁηÈÚ· ·ÛıÂÓ›˜ Ì ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ Î·È Ó· ηÙ¢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, primary health care.
∂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›·˜ Î·È Ù˘ ¤Ú¢ӷ˜ fiÏÔ Î·È ÈÔ Û˘¯Ó¿ ‰È·ÁÈÁÓÒÛÎÔÓÙ·È ÌÂÙ·‚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 ÌÂÁ·Ï‡ÙÂÚÔ ·fi 500.000 ηÙÔ›ÎÔ˘˜, ·ÔÎÙ¿ ȉȷ›ÙÂÚÔ ÂӉȷʤÚÔÓ Î·ıÒ˜: ·) ∏ ÏÂÈÔ„ËÊ›· ÙˆÓ ÁÈ·ÙÚÒÓ Ô˘ ÂÚÁ¿˙ÔÓÙ·Ó ÛÙ· ΤÓÙÚ· ˘Á›·˜ ̤¯ÚÈ ÚfiÛÊ·Ù· ‹Ù·Ó ·ÓÂȉ›Î¢ÙÔÈ Ô˘ ÂÎÏ‹ÚˆÓ·Ó ÙËÓ ˘Ô¯ÚˆÙÈ΋ ıËÙ›· ˘·›ıÚÔ˘, ¯ˆÚ›˜ ÙËÓ Î·Ù¿ÏÏËÏË Âη›‰Â˘ÛË Î·È ÂÌÂÈÚ›· ÒÛÙ ӷ ·Ó·ÁÓˆÚ›˙Ô˘Ó ¤ÁηÈÚ· ÙȘ ÎÏÈÓÈΤ˜ 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¿ÙˆÓ ÛÙËÓ ∂ÏÏ¿‰· Î·È ÙÔ Â͈ÙÂÚÈÎfi. ‚) ™ÙȘ ·ÔÌÔӈ̤Ó˜ ·ÁÚÔÙÈΤ˜ ÂÚÈÔ¯¤˜ Ù˘ ∫Ú‹Ù˘, fiÔ˘ Ê·›ÓÂÙ·È fiÙÈ ÂÓÙÔ›˙ÂÙ·È Ë ÏÂÈÔÓfiÙËÙ· 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 Â·Ê‹ 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· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤ÁÈÓ ȉȷ›ÙÂÚË ÚÔÛ¿ıÂÈ· ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Ù˘ ÌÔÓ¿‰·˜ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÛÙËÓ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋. øÛÙfiÛÔ, ÚԤ΢„·Ó ·ÚÎÂÙ¤˜ ‰˘ÛÎÔϛ˜ ÁÈ·Ù› ÂÎÙfi˜ ·fi ÙËÓ ·Ó·Ú΋ ÂÓË̤ڈÛË ÙˆÓ ÁÈ·ÙÚÒÓ Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ (¶ºÀ), ˘¿Ú¯Ô˘Ó ÔÏϤ˜ ·ÔÌÔӈ̤Ó˜ Î·È ‰˘ÛÚfiÛÈÙ˜ ÂÚÈÔ¯¤˜ Û ̷ÎÚÈÓ¤˜ ·ÔÛÙ¿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› Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤Ó· ‰›ÎÙ˘Ô ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ Û˘ÓÂÚÁ·Û›·˜ ÙÔ˘ ∆Ô̤· ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ Î·È 10 ΤÓÙÚˆÓ ˘Á›·˜. ∂ÈϤÔÓ, Â›Ó·È È‰È·›ÙÂÚ· ÛËÌ·ÓÙÈÎfi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÌÂÙ¿ ÙÔ 1995 ÂÎÙfi˜ ·fi ÙÔ˘˜ ÂȉÈÎÂ˘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›·˜ ÌÂٷ͇ Ù˘ ∫ÏÈÓÈ΋˜ ∫ÔÈÓˆÓÈ΋˜ π·ÙÚÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘ Î·È Ù˘ ªÔÓ¿‰·˜ ªÂÙ·‚ÔÏÈÎÒÓ ¡fiÛˆÓ Ù˘ ¶·È‰È·ÙÚÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ °ÂÓÈÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ ∏Ú·ÎÏ›Ԣ (¶·°¡∏), Ì ÛÎÔfi ÙËÓ ·Ó›¯Ó¢ÛË Î·È ¤ÁηÈÚË ‰È¿ÁÓˆÛË ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ ÛÙËÓ ∫Ú‹ÙË. ∏ ‰ÈÂÚ‡ÓËÛË 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·ÈÚÂÙÈο 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˘ ¡ÔÛÔÎÔÌ›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΋˜ ÌÂϤÙ˘ 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¿˙ÔÓÙ·È ÛÙË ÚˆÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· ˘Á›·˜ ÛÙË ‰È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·.
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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 8 ΤÓÙÚ· ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ÛÙÔ ÓËÛ› (™‹ÏÈ, ¶¤Ú·Ì·, ∞ÓÒÁÂÈ·, ∫¿ÓÙ·ÓÔ˜, ∫·ÛÙ¤ÏÏÈ, ªÔ›Ú˜, ∞Ú¯¿Ó˜ Î·È ¡Â¿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˘ÙÈΤ˜ ÚÔηٷÚÎÙÈΤ˜ Û˘Ó·ÓÙ‹ÛÂȘ ÛÙÔ ¶·ÓÂÈÛÙ‹ÌÈÔ ∫Ú‹Ù˘. ¶ÚÈÓ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÚÔÁÚ¿ÌÌ·ÙÔ˜, ηıÔÚ›ÛÙËΠ¤Ó·˜ ηٿÏÔÁÔ˜ Ì ÎÚÈÙ‹ÚÈ· ÂÈÛ·ÁˆÁ‹˜ ·ÛıÂÓÒÓ ÛÙË ÌÂϤÙË Ô˘ ‚·Û›ÛÙËΠ۠ÂȉÈο ‹ ÌË ÂȉÈο ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ηÈ
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¶·È‰È·ÙÚÈ΋ 2003;66:133-139
Paediatriki 2003;66:133-139
Û˘ÌÙÒÌ·Ù· Ô˘ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·ÛıÂÓ›˜ Ì ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· (7-9). O ηٿÏÔÁÔ˜ Ì ٷ ÎÚÈÙ‹ÚÈ·, Û‡Ìʈӷ Ì ٷ ÔÔ›· ÔÈ ·ÛıÂÓ›˜ ·Ú·¤ÌÊıËÎ·Ó Ì ÙËÓ ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ, Ê·›ÓÂÙ·È ÛÙÔÓ ¶›Ó·Î· 1. OÈ ÁÈ·ÙÚÔ› Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ¤ÏÂÁ¯·Ó ÙËÓ ·ÚÔ˘Û›· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ·˘ÙÒÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ÙÔ˘˜ Î·È ·Ú¤ÂÌ·Ó ·ÛıÂÓ›˜ Ì 1 ‹ ÂÚÈÛÛfiÙÂÚ· ÎÚÈÙ‹ÚÈ· ÛÙË ÌÔÓ¿‰· ÂÓ‰ÔÁÂÓÒÓ ÓÔÛËÌ¿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 ÏÂÙÔÌÂÚ‹ 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›·, ÛÙÔ ÈÛÙÔÚÈÎfi Î·È ÙËÓ ÂȉÈ΋ ηÙ‡ı˘ÓÛË Ô˘ ‰fiıËΠ̠‚¿ÛË ÙȘ Èı·Ó¤˜ ‰È·ÁÓÒÛÂȘ Ô˘ ηıÔÚ›ÛÙËÎ·Ó ·fi ·È‰ÔÓ¢ÚÔÏfiÁÔ. ™Â fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ¤ÁÈÓ ·Ó¿Ï˘ÛË ·›Ì·ÙÔ˜ (ÁÂÓÈ΋ ÂͤٷÛË ·›Ì·ÙÔ˜ Î·È ÚÔÛ‰ÈÔÚÈÛÌfi˜: ËÏÂÎÙÚÔÏ˘ÙÒÓ, ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ, ÁÏ˘Îfi˙˘, ·ÂÚ›ˆÓ ·›Ì·ÙÔ˜, ÎÚ·ÙÈÓ›Ó˘, Ô˘Ú›·˜, Ô˘ÚÈÎÔ‡ ÔͤԘ, ÎÚ·ÙÈÓÔʈÛÊÔÎÈÓ¿Û˘ (CPK), ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘, Á·Ï·ÎÙÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘ (LDH), ÙÚÈÁÏ˘ÎÂÚȉ›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, ·Ì̈ӛ·˜ Î·È Î·ÚÓÈÙ›Ó˘. ∂ÈϤÔÓ, ¤ÁÈÓ ËÏÂÎÙÚÔÂÁÎÂÊ·ÏÔÁÚ¿ÊËÌ· (∏∂°), ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ (CT scan) ηÈ, fiÔ˘ ÎÚ›ıËΠÛÎfiÈÌÔ, 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 ‚¿ÛË Ù· ·ÔÙÂϤÛÌ·Ù· ·fi ÙÔÓ ·Ú¯ÈÎfi ÂÚÁ·ÛÙËÚÈ·Îfi Î·È ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô ¤ÁÈÓ ¤ÏÂÁ¯Ô˜ ÁÈ· ÔÚÁ·ÓÈΤ˜ ÔÍÂÔ˘Ú›Â˜ (·Ó¿Ï˘ÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Ô‡ÚˆÓ Ì GC/MS), ÚÔÛ‰ÈÔÚÈÛÌfi˜ ·ÌÈÓÔͤˆÓ ÛÙÔ Ï¿ÛÌ· Î·È Ù· Ô‡Ú·, ÂÓÒ Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Ú·ÁÌ·ÙÔÔÈ‹ıËΠ·Ó¿Ï˘ÛË VLCFA (very long chain fatty acids) ÛÙÔÓ ÔÚfi. ™Â ÂÈÏÂÁ̤Ó˜ ÂÚÈÙÒÛÂȘ ¤ÁÈÓ ÊfiÚ-
¶¤Ú·Ì·
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 ÁÂÓÂÙÈÎÔ‡ ˘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·‚ÔÏÈÎÒÓ Î¤ÓÙÚˆÓ 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›· ÔÈ ÁÈ·ÙÚÔ› Ù˘ ÚˆÙÔ‚¿ıÌÈ·˜ ÊÚÔÓÙ›‰·˜ ˘Á›·˜ ·Ú¤ÂÌ„·Ó ÙÔ˘˜ ·ÛıÂÓ›˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌ›Ô. ¶·Ú·¤ÌÊıËÎ·Ó Û˘ÓÔÏÈο 112 ·ÛıÂÓ›˜, 17 (15,2%) ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ‰È·ÈÛÙÒıËΠfiÙÈ Â›¯·Ó ÁÓˆÛÙfi ÌÂÙ·‚ÔÏÈÎfi ÓfiÛËÌ·. ∏ ÓÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË (49 ·ÛıÂÓ›˜) Î·È ÔÈ Â›ÌÔÓÔÈ Û·ÛÌÔ› (36 ·ÛıÂÓ›˜) ‹Ù·Ó Ù· Û˘ÓËı¤ÛÙÂÚ· Û˘ÌÙÒÌ·Ù· ‹ ¯·Ú·ÎÙËÚÈÛÙÈο ÁÈ· Ù· ÔÔ›· ÔÈ ·ÛıÂÓ›˜ ·Ú·¤ÌÊıËηÓ. ∆· Û˘ÓËı¤ÛÙÂÚ· ·fi Ù· ÌË Ó¢ÚÔÏÔÁÈο Û˘ÌÙÒÌ·Ù· ‹ ¯·Ú·ÎÙËÚÈÛÙÈο Ô˘ ¤ıÂÛ·Ó ÙËÓ ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ‹Ù·Ó Ë ·‰È¢ÎÚ›ÓÈÛÙ˘ ·ÈÙÈÔÏÔÁ›·˜, ¤ˆ˜ ÙfiÙÂ, ηı˘ÛÙ¤ÚËÛË Ù˘ ·Ó¿Ù˘Í˘ Î·È ÙÔ Â›ÌÔÓÔ ¤Î˙ÂÌ·. ∆· Û˘¯ÓfiÙÂÚ· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËÎ·Ó ‹Ù·Ó ÔÈ ÔÚÁ·ÓÈΤ˜ ÔÍÂÔ˘Ú›Â˜. ¢È·ÁÓÒÛÙËÎ·Ó Û˘ÓÔÏÈο 8 ·ÛıÂÓ›˜ Ì ÔÚÁ·ÓÈ΋ ÔÍÂÔ˘Ú›· (47%), 3 ·ÛıÂÓ›˜ Ì ÁÏ˘ÎÔÁÔÓÈ¿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·‚ÔÏÈÛÌfi ÙˆÓ ·ÌÈÓÔͤˆÓ (5,8%) Î·È 1 ·ÛıÂÓ‹˜ Ì ÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂÈ· (5,8%). ∆· ÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËÎ·Ó Î·È Ë ËÏÈΛ· ÙˆÓ ·ÛıÂÓÒÓ Ê·›ÓÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 2. ™˘˙‹ÙËÛË ∏ ·ÚÔ‡Û· ÈÏÔÙÈ΋ ÌÂϤÙË ‰ÂÓ ÛÙÂÚÂ›Ù·È ÌÂıÔ‰ÔÏÔÁÈÎÒÓ ÂÚÈÔÚÈÛÌÒÓ. O ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ÙˆÓ
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¶·È‰È·ÙÚÈ΋ 2003;66:133-139
Paediatriki 2003;66:133-139
¶›Ó·Î·˜ 1. ™˘ÌÙÒÌ·Ù· Î·È ‰È·Ù·Ú·¯¤˜ Ô˘ ·ÍÈÔÏÔÁ‹ıËÎ·Ó (·ÚÈıÌfi˜ ·ÛıÂÓÒÓ ·Ó¿ ηÙËÁÔÚ›·) ™˘ÌÙÒÌ·Ù·*
∞ÛıÂÓ›˜ (·ÚÈıÌfi˜)
¡ÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË ªË ÂÏÂÁ¯fiÌÂÓÔÈ Û·ÛÌÔ› ∫·ı˘ÛÙ¤ÚËÛË Ù˘ ·Ó¿Ù˘Í˘ ∂›ÌÔÓÔ ¤Î˙ÂÌ· ¢È·Ù·Ú·¯¤˜ ÙÔ˘ ÏfiÁÔ˘ ™˘ÌÙÒÌ·Ù· ¿ÛËÙ˘ ÂÁÎÂÊ·Ï›Ùȉ·˜ ¶˘Ú·ÌȉÈ΋ Û˘Ó‰ÚÔÌ‹ ∞˘ÙÈÛÙÈ΋ Û˘ÌÂÚÈÊÔÚ¿ ™˘ÌÙÒÌ·Ù· ÂÚÈÊÂÚÈ΋˜ Ó¢ÚÔ¿ıÂÈ·˜ ÀÔÁÏ˘Î·ÈÌ›·
49 36 18 14 9 8 8 7 5 5
* 36 ·ÛıÂÓ›˜ ·ÚÔ˘Û›·˙·Ó ≥2 Û˘ÌÙÒÌ·Ù·
Û˘ÌÌÂÙ¯fiÓÙˆÓ ·ÛıÂÓÒÓ, Ô ÔÔ›Ô˜ ‰ÂÓ ·ÓÙÈÚÔۈ‡ÂÈ ÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi Î·È ÙÔ ÌË ÛÙ·ıÌÈṲ̂ÓÔ 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 fiÙÈ Ù· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· ÛÙËÓ ∫Ú‹ÙË ‰ÂÓ Â›Ó·È ÙfiÛÔ Û¿ÓÈ·, ·ÊÔ‡ ÛÙÔ ‚Ú·¯‡ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô˘ ‰ÈÂÍ‹¯ıË ·˘Ù‹ Ë ÌÂϤÙË ÙÂÎÌËÚÈÒıËÎÂ Ë ‰È¿ÁÓˆÛË Û 17 ·fi ÙÔ˘˜ 112 ·ÛıÂÓ›˜ Ô˘ ·Ú·¤ÌÊıËÎ·Ó (15,2%) (¶›Ó·Î·˜ 2). ™Â 12 ·fi Ù· 17 ÓÔÛ‹Ì·Ù· Ô˘ ‰È·ÁÓÒÛıËÎ·Ó ‹Ù·Ó ‰˘Ó·Ù‹ Ë ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·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¯ÂÙÈο ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ·. ™˘ÓÂÒ˜, Ë ‚Ô‹ıÂÈ· Ô˘ ¯ÔÚËÁ‹ıËΠ‹Ù·Ó ΢ڛˆ˜ Û˘Ìو̷ÙÈ΋ Î·È ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ ÎÚ›ıËΠ·Ó·ÚΤ˜. ÷ڷÎÙËÚÈÛÙÈΤ˜ Â›Ó·È ÔÈ ÙÚÂȘ ÂÚÈÙÒÛÂȘ ÙˆÓ ÁÏ˘ÎÔÁÔÓÈ¿ÛÂˆÓ Ô˘ ‰È·ÁÓÒÛÙËηÓ. OÈ ÁÏ˘ÎÔÁÔÓÈ¿ÛÂȘ, ·Ó Î·È Â›Ó·È Û¿ÓȘ ÎÏËÚÔÓÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜, ·Ó·Ê¤ÚÔÓÙ·È Û¯ÂÙÈο Û˘¯ÓfiÙÂÚ· ÛÙËÓ ÂÏÏËÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›· (10-12). ª›· ·ÛıÂÓ‹˜ ËÏÈΛ·˜ 26 ÂÙÒÓ, ¿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 ¯ˆÚ›˜ ‰È·ÁÓˆÛÙÈο Â˘Ú‹Ì·Ù· ·fi ÙÔÓ ÂοÛÙÔÙ ÎÏÈÓÈÎÔÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô. OÈ ÁÔÓ›˜ Ù˘ ÂÓÛÙÈÎÙˆ‰Ò˜ ¯ÔÚËÁÔ‡Û·Ó ·fi ÌfiÓÔÈ ÙÔ˘˜ Ôχ Û˘¯Ó¿ Á‡̷ٷ ÏÔ‡ÛÈ· Û ˘‰·Ù¿ÓıڷΘ. §fiÁˆ Ù˘ ·Ó·ÚÎÔ‡˜ ıÂڷ›·˜, Ì ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘ Ë ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·Û ‚·ÚÈ¿ ÔÛÙÂÔfiÚˆÛË, ÎÔÏ›Ùȉ· Î·È Â›¯Â ¯·ÌËÏfi ·Ó¿ÛÙËÌ·. ∞ÚÎÂÙ¿ Û˘¯Ó¿ ·ÚÔ˘Û›·˙ ÏÔÈÌÒÍÂȘ, ·ÓÙÈÌÂÙˆÈ˙fiÙ·Ó Û˘Ìو̷ÙÈο 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
136
·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˘ Û ÛËÌ·ÓÙÈÎfi ‚·ıÌfi. ∏ ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·Û ‡ÊÂÛË ÙˆÓ ÂΉËÏÒÛÂˆÓ ·fi ÙÔ ÂÙÈÎfi Î·È ÔÈ ÏÔÈÌÒÍÂȘ ÂÚÈÔÚ›ÛÙËÎ·Ó ÛËÌ·ÓÙÈο, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ‚ÂÏÙȈı› Ë ÔÈfiÙËÙ· Ù˘ ˙ˆ‹˜ Ù˘. OÈ ¿ÏϘ ‰‡Ô ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ Ì ÁÏ˘ÎÔÁÔÓ›·ÛË ‰ÂÓ Î·Ù¤ÛÙË ‰˘Ó·Ùfi Ó· ‚ÔËıËıÔ‡Ó ·Ó¿ÏÔÁ·. ∫·È ÔÈ ‰‡Ô ·ÛıÂÓ›˜, ÏfiÁˆ ÙˆÓ ÔÏÏ·ÏÒÓ ˘ÔÁÏ˘Î·ÈÌÈÎÒÓ ÎÚ›ÛÂˆÓ ·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¿ÙˆÓ Ô˘ ‰È·ÁÓÒÛıËÎ·Ó ‚Ú¤ıËΠӷ Â›Ó·È ·˘Ù‹ ÙˆÓ ÔÚÁ·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˘ ÓËȷ΋˜ 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 ¿ÏÏˆÓ ÂȉËÌÈÔÏÔÁÈÎÒÓ 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, ÂÓ Ì¤Ûˆ 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 ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ¤¯ÂÈ Û‹ÌÂÚ· Û¯ÂÙÈο ηϋ ÔÈfiÙËÙ· ˙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›·˙ ٷ ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÁÓˆÚ›ÛÌ·Ù· Ù˘ ÓfiÛÔ˘ (Û·ÛÌÔ›, ÂÍ¿ÓıËÌ·). ∆Ô ÌfiÓÔ Â‡ÚËÌ· ·fi ÙËÓ ÎÏÈÓÈ΋ ÂÎÙ›ÌËÛË ‹Ù·Ó Ë ·ÚÔ˘Û›· ·˘ÙÈÛÙÈ΋˜ Û˘ÌÂÚÈÊÔÚ¿˜. ∞fi fiÛÔ ÁÓˆÚ›˙Ô˘ÌÂ Â›Ó·È Ë ‰Â‡ÙÂÚË ÂÚ›ÙˆÛË ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· Ô˘ ‰È·ÁÈÁÓÒÛÎÂÙ·È ·ÛıÂÓ‹˜ Ì ·Ó¿ÚÎÂÈ· ‚ÈÔÙÈÓȉ¿Û˘ Î·È ·˘ÙÈÛÙÈ΋ Û˘ÌÂÚÈÊÔÚ¿ (15,16). O ·ÛıÂÓ‹˜ ·ÓÙ·ÔÎÚ›ıËΠÂÓÙ˘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΋ ˘ÔÛÙ‹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˘. ¶ÚÔÁÂÓÓËÙÈÎfi˜ ¤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 ÙË ÓfiÛÔ. ∏ ‰Â‡ÙÂÚË ·ÛıÂÓ‹˜ Ì ÓfiÛÔ Ï˘ÛÔÛۈ̷ٛˆÓ
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·137
¶·È‰È·ÙÚÈ΋ 2003;66:133-139
Paediatriki 2003;66:133-139
¶›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·ÁÓÒÛıËÎ·Ó ªÂÙ·‚ÔÏÈÎfi ÓfiÛËÌ·
∞ÚÈıÌfi˜ ·ÛıÂÓÒÓ Ô˘ ‰È·ÁÓÒÛıËÎ·Ó (%)
OÚÁ·ÓÈ΋ Ô͢Ԣڛ· 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 °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˜ ¡fiÛÔ˜ Canavan (12 ÌËÓÒÓ) º˘ÏÔÛ‡Ó‰ÂÙË ·‰ÚÂÓÔÏ¢ÎÔ‰˘ÛÙÚÔÊ›· (8 ÂÙÒÓ) §˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù· ∞Ó¿ÚÎÂÈ· ·-Ì·ÓÓÔÛȉ¿Û˘ (3 ÂÙÒÓ) ¡fiÛÔ˜ Gaucher Ù‡Ô˘ I (30 ÂÙÒÓ) ¢È·Ù·Ú·¯¤˜ ÛÙÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙˆÓ ·ÌÈÓÔͤˆÓ ¡fiÛÔ˜ ÔÛÌ‹˜ Ô‡ÚˆÓ ÛÊÂÓ‰¿ÌÔ˘ (Maple syrup disease) (2 ÌËÓÒÓ) ªÈÙÔ¯ÔӉȷΤ˜ ÂÁÎÂÊ·ÏÔ¿ıÂȘ ™˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ π Î·È πππ (2 ÂÙÒÓ) ™‡ÓÔÏÔ ·ÛıÂÓÒÓ Ô˘ ‰È·ÁÓÒÛıËηÓ
˘¤ÊÂÚ ·fi ÙËÓ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ Gaucher. ∏ ÓfiÛÔ˜ Gaucher Â›Ó·È ÙÔ Û˘¯ÓfiÙÂÚÔ ·fi Ù· Ï˘ÛÔÛÛˆÌȷο ÓÔÛ‹Ì·Ù· Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÂÁ¿ÏË ÎÏÈÓÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ· (17). H ·ÛıÂÓ‹˜ Ì ÓfiÛÔ Gaucher ÛÙË ÌÂϤÙË ·˘Ù‹ ‰È·ÁÓÒÛıËΠ۠ÌÂÁ¿ÏË Û¯ÂÙÈο ËÏÈΛ· Î·È ·Ú·¤ÌÊıËΠÛÙË ÌÔÓ¿‰· ÌÂÙ·‚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 ·ÏÏÔÈÒÛÂˆÓ Ù˘ ÓfiÛÔ˘, ·ÚÔ˘Û›·˙ ÂÈϤÔÓ Â›ÌÔÓË ÂÎ˙ÂÌ·ÙÔÂȉ‹ ‰ÂÚÌ·Ù›Ùȉ· ¿ÎÚˆÓ Î·È ÚÔÛÒÔ˘. ¶·Ú’ fiÏÔ Ô˘ Û ·ÛıÂÓ›˜ Ì ¿ÏÏ· Ï˘ÛÔÛÛˆÌȷο ÓÔÛ‹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·ÈÓÔÙ˘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˘ÂÏfi Ô‰‹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˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, Ë ·ÛıÂÓ‹˜ Ù¤ıËΠ۠ÂÓ˙˘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¢ÙÈ΋ Î·È ‰È·ÈÙËÙÈ΋ ·ÁˆÁ‹ ·ÚÔ˘ÛÈ¿˙ÂÈ Û‹ÌÂÚ· Ê˘ÛÈÔ-
8 (47%)
3 (17,6%)
2 (11,7%)
2 (11,7%)
1 (5,8%) 1 (5,8%) 17
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˘ Ì ÙÔÓ ÔÔ›Ô ÎÏËÚÔÓÔÌÔ‡ÓÙ·È ÔÈ ÌÈÙÔ¯ÔÓ‰ÚÈÔ¿ıÂȘ (20,21). ∏ ·ÓÙÈÌÂÙÒÈÛË ‹Ù·Ó Û˘Ìو̷ÙÈ΋, ÂÓÒ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ·Ú·Û¯¤ıËΠοı „˘¯ÔÏÔÁÈ΋ Î·È ÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË. ™˘Ìو̷ÙÈ΋ ıÂڷ›·, „˘¯ÔÏÔÁÈ΋ Î·È ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË ·Ú·Û¯¤ıËΠ۠fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘, ·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 ÌfiÓÔ 70 ·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˜ ·ÔÌÔӈ̤Ó˜, ÂÈÎÚ·ÙÔ‡Ó È‰È¿˙Ô˘Û˜ ÎÔÈÓˆÓÈΤ˜ Î·È ÔÏÈÙÈÛÌÈΤ˜ Û˘Óı‹Î˜ Î·È Ë Â·Ê‹ Ì ÙÔÓ È·ÙÚfi Â›Ó·È Û˘¯Ó¿ ÂÍ·ÈÚÂÙÈο ‰‡ÛÎÔÏË. ™Â ÔÏϤ˜ ÔÈÎÔÁ¤ÓÂȘ ıˆÚÂ›Ù·È "ÛÙ›ÁÌ·” Ë ‡·ÚÍË ÂÓfi˜ ·ÙfiÌÔ˘ Ì ÓÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË ‹ ¿ÏÏ· Û˘ÌÙÒÌ·Ù· ·fi ÙÔ Ó¢ÚÈÎfi Û‡ÛÙËÌ·, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ˘¿Ú¯Ô˘Ó
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‰˘ÛÎÔϛ˜ ÛÙËÓ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ·ÔηٿÛÙ·ÛË fiÏˆÓ ÙˆÓ ÌÂÏÒÓ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜ (Á¿ÌÔ˜, ‡ÚÂÛË ÂÚÁ·Û›·˜). ∏ ·ÙÂÏ‹˜ Î·È ÂÛÊ·Ï̤ÓË Û˘¯Ó¿ ·ÓÙ›ÏË„Ë Î·È ÂÓË̤ڈÛË ÙÔ˘ ÏËı˘ÛÌÔ‡ Ù˘ ÂÚÈʤÚÂÈ·˜ 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›·˜ ÂÓËÌÂÚÒıËÎ·Ó Î·È Âηȉ‡ÙËÎ·Ó Û¯ÂÙÈο Ì ÙË ‰È¿ÁÓˆÛË Î·È ÙȘ ‰˘Ó·ÙfiÙËÙ˜ ·ÓÙÈÌÂÙÒÈÛ˘ Î·È ÁÂÓÂÙÈ΋˜ Û˘Ì‚Ô˘Ï¢ÙÈ΋˜ ÛÙ· ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∞˘ÙÔ› Ì ÙË ÛÂÈÚ¿ ÙÔ˘˜, ÏfiÁˆ Ù˘ ηχÙÂÚ˘ ·ʋ˜ Ô˘ ¤¯Ô˘Ó Ì ÙÔ˘˜ ηÙÔ›ÎÔ˘˜ ÙˆÓ ·ÁÚÔÙÈÎÒÓ ÂÚÈÔ¯ÒÓ, ÌfiÚÂÛ·Ó Ó· ¢·ÈÛıËÙÔÔÈ‹ÛÔ˘Ó ÙÔÓ ÏËı˘ÛÌfi Ù˘ ˘·›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¤ÂÌ·Ó ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˘fiÓÔÈ· ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ. ªÂ ÙË Û˘ÓÂÚÁ·Û›· ÙˆÓ ÓÔÛÔÎÔÌÂÈ·ÎÒÓ È·ÙÚÒÓ Î·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, ·Ïfi Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ ˘„ËÏ‹ ¢·ÈÛıËÛ›·, fiˆ˜ ·Ô‰Â›¯ıËΠ·fi ÙÔ Û¯ÂÙÈο ˘„ËÏfi ÔÛÔÛÙfi ‰È·ÁÓÒÛÂˆÓ ÛÙÔ 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΋ ·ÓÙÈÌÂÙÒÈÛË, ÁÂÓÂÙÈ΋ Û˘Ì‚Ô˘Ï¢ÙÈ΋ Î·È ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋ ˘ÔÛÙ‹ÚÈÍË ·ÛıÂÓÒÓ Î·È ÔÈÎÔÁÂÓÂÈÒÓ Ì ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∏ ÚÔÛÂÎÙÈ΋ ·ÍÈÔÏfiÁËÛË ÂÓfi˜ ·ÚÈıÌÔ‡ ÎÏÈÓÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ‹ Û˘ÌÙˆÌ¿ÙˆÓ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ ÛÙËÓ ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È ¤ÌÌÂÛ· ÛÙËÓ ¤ÁηÈÚË ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË, fiÔ˘ ·˘Ù‹ Â›Ó·È Û‹ÌÂÚ· ÂÊÈÎÙ‹. ŸÌˆ˜, ·ÎfiÌË Î·È fiÙ·Ó ÔÈ ‰˘Ó·ÙfiÙËÙ˜ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ Â›Ó·È ÂÚÈÔÚÈṲ̂Ó˜, Â›Ó·È ÛËÌ·ÓÙÈ΋ Î·È ÂÈÙ·ÎÙÈ΋ Ë ·ÚÔ¯‹ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈ΋˜ ˘ÔÛÙ‹ÚÈ͢ Î·È ÁÂÓÂÙÈ΋˜ 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.
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HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-03-2002 HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 20-12-2002 ¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ªÈ¯·ËÏ›‰Ô˘ ∂ϤÓË ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶ÂÚÈÊÂÚÂÈ·Îfi ¶·ÓÂÈÛÙËÌÈ·Îfi °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú¿ÎÏÂÈÔ, ∫Ú‹ÙË
¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›· OÈ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ ÛÙ· ·È‰È¿ ÂËÚ¿˙Ô˘Ó ÙË ‰È·ÙÚÔÊÈ΋ ÚfiÛÏË„Ë Î·È ·Ó¿Ù˘ÍË1 ™ÎÔfi˜: ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Ù˘ ·Ó¿Ù˘Í˘ Î·È Ù˘ ‰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 ÙȘ ÙÚÔÊÈΤ˜ ·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˘˜ Î·È ‰Â›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· ηٷÁÚ·Ê‹˜ ÙÚÔʛ̈Ó. ŒÓ· ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ ¯ÚËÛÈÌÔÔÈ‹ıËΠÁÈ· ÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÙÚÔÊÈÎÒÓ ·ÏÏÂÚÁÈÒÓ Î·È ¿ÏÏˆÓ ÌÂÙ·‚ÏËÙÒÓ. ™Â ·˘Ù‹ ÙËÓ ÚÔÔÙÈ΋, ‰È·ÛÙ·˘ÚÔ‡ÌÂÓË ÌÂϤÙË Û˘ÌÌÂÙ›¯·Ó 99 ·È‰È¿ Ì ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ (·ÛıÂÓ›˜) Ì ̤ÛË ËÏÈΛ· Ù· 3,7±2,3 ¤ÙË Î·È 99 ·È‰È¿ ¯ˆÚ›˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ (‰Â›ÁÌ· ·Ó·ÊÔÚ¿˜) Ì ̤ÛË ËÏÈΛ· Ù· 4,1±2,4 ¤ÙË. ∏ ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË ‰ÈÂÍ‹¯ıË Ì ÙÔ CochranMantel-Haeszel Statistics, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÁÂÓÈ΋ Û˘Û¯¤ÙÈÛË Î·È Fisher Exact Test. ∞ÔÙÂϤÛÌ·Ù·: ∆· ·È‰È¿ Ì ‰‡Ô ‹ ÂÚÈÛÛfiÙÂÚ˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ ›¯·Ó ¯·ÌËÏfiÙÂÚÔ ·Ó¿ÛÙËÌ·, Ì ÎÚÈÙ‹ÚÈÔ ÙȘ η̇Ϙ ‡„Ô˘˜-ËÏÈΛ·˜, Û ۯ¤ÛË Ì ÂΛӷ Ì ̛· ÙÚÔÊÈ΋ ·ÏÏÂÚÁ›· (p<0,05). ¶ÂÚÈÛÛfiÙÂÚÔ ·fi ÙÔ 2,5% ÙˆÓ ·È‰ÈÒÓ Î·È ÙˆÓ ‰‡Ô ÔÌ¿‰ˆÓ ηٷӿψÓ ÏÈÁfiÙÂÚÔ ·fi 6,7% Ù˘ ËÌÂÚ‹ÛÈ·˜ Û˘ÓÈÛÙÒÌÂÓ˘ ÔÛfiÙËÙ·˜ ÁÈ· ÙÔ ·Û‚¤ÛÙÈÔ, ÙË ‚ÈÙ·Ì›ÓË D Î·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· ÌÈÎÚfiÙÂÚ˘ ·fi ÙË Û˘ÓÈÛÙÒÌÂÓË ÚfiÛÏ˄˘ ·Û‚ÂÛÙ›Ô˘ Î·È ‚ÈÙ·Ì›Ó˘ D Û ·È‰È¿ Ì ÙÚÔÊÈ΋ ·ÏÏÂÚÁ›· ‹Ù·Ó ÏÈÁfiÙÂÚË, ·Ó ÙÔ ·È‰› ÂÏ¿Ì‚·Ó ‰È·ÙÚÔÊÈΤ˜ Û˘Ì‚Ô˘Ï¤˜ (p<0,05) ‹ ηٷӿψÓ ¤Ó· ·ÛʷϤ˜ ‚ÚÂÊÈÎfi/ÓÂÔÁÓÈÎfi ˘ÔηٿÛÙ·ÙÔ ‹ ˘ÔηٿÛÙ·ÙÔ ÛfiÁÈ·˜. ™˘ÌÂÚ¿ÛÌ·Ù·: ¶·È‰È¿ Ì ‰È·ÁÓˆṲ̂Ó˜ ÙÚÔÊÈΤ˜ ·ÏÏÂÚÁ›Â˜ ¯ÚÂÈ¿˙ÔÓÙ·È ÂÙ‹ÛÈ· ‰È·ÙÚÔÊÈ΋ ·ÍÈÔÏfiÁËÛË ÁÈ· ÙËÓ ÚfiÏË„Ë ÚÔ‚ÏËÌ¿ÙˆÓ ·Ó¿Ù˘Í˘ ‹ ·Ó·ÚÎÔ‡˜ ÚfiÛÏ˄˘ ıÚÂÙÈÎÒÓ Û˘ÛÙ·ÙÈÎÒÓ. ∆· ·È‰È¿ Ì ·ÏÏÂÚÁ›· ÛÙÔ Á¿Ï· ‹ ÔÏϷϤ˜ ·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 ÂÓۈ̿وÛË ÂÓ·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˘.
1 Christie L, Hine RJ, Parker JG, Burks W Food allergies in children affect nutrient intake and growth J Am Diet Assoc 2002;102:1648-1651
∞ÈÌÈÏ›· µ·ÛÈÏÔÔ‡ÏÔ˘
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∞¡∞™∫O¶∏™∏
Paediatriki 2003;66:89-96
REVIEW ARTICLE
∏ 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
¶ÂÚ›ÏË„Ë: À¿Ú¯Ô˘Ó ÌÂÚÈο ÌË ÔÚÁ·ÓÈο ·›ÙÈ· Ù˘ ·Ó¿ÚÎÂÈ·˜ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Ô˘ ÌÔÚÔ‡Ó Ó· ·Ô‰ÔıÔ‡Ó Û ÁÂÓÂÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ¿ÍÔÓ· ˘Ôı·Ï¿ÌÔ˘-˘fiÊ˘Û˘. ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤ÙÚ„·Ó ÙËÓ Ù·˘ÙÔÔ›ËÛË ÂÓfi˜ ·ÚÈıÌÔ‡ ÁÔÓȉ›ˆÓ Ô˘ ÂÓ¤¯ÔÓÙ·È ¿ÌÂÛ· ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ Î·È ÙȘ ÂÍ·ÚÙÒÌÂÓ˜ ·fi ·˘Ù‹ ÏÂÈÙÔ˘ÚÁ›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˘ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. ∞˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÛÙË Û‡ÓıÂÛË ‹ ÛÙË ‰Ú¿ÛË Ù˘ GH ÌÔÚÔ‡Ó Ó· ÚÔηϤÛÔ˘Ó Ì›· ÌÂÁ¿ÏË ÔÈÎÈÏ›· ÛÙÔÓ ÎÏÈÓÈÎfi Ê·ÈÓfiÙ˘Ô ÙˆÓ ·ÛıÂÓÒÓ. À¿Ú¯Ô˘Ó Ù¤ÛÛÂÚȘ ‰È·ÊÔÚÂÙÈÎÔ› Ù‡ÔÈ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘: Ô Ù‡Ô˜ π∞, πµ, ππ Î·È πππ. ∂ÈÚfiÛıÂÙ·, ¤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‹ÛÂˆÓ ÌÔÚ› Ó· ÂÍ·ÛÊ·Ï›ÛÂÈ Ì›· ÈÔ ÛˆÛÙ‹ ÚÔÛ¤ÁÁÈÛË ÛÙÔ˘˜ ıÂڷ¢ÙÈÎÔ‡˜ ¯ÂÈÚÈÛÌÔ‡˜.
Abstract: Some non-organic causes for growth hormone deficiency (GHD) can be attributed to genetic defects within the hypothalamo-pituitary axis. Recent advances have led to the characterization of a number of genes which are directly involved in pituitary development and related functions. Micromutations within the growth hormone (GH) and GH-releasing hormone receptor gene (GHRH) have been detected as a cause of isolated GHD. The resulting abnormalities in the synthesis or the activity of GH can give rise to a wide variation in the clinical phenotype of the patient. Four different types of isolated GH deficiency (IGHD) have been described: type IA, type IB and types II and III. In addition, increasing numbers of patients with combined pituitary hormone deficiencies (CGHD) have been reported, presenting mutations within pituitary transcription factors Pit-1, Prop-1, LHX3 and Hesx-1. These various defects can be observed with different frequencies in clinical practice. The use of molecular and genetic diagnostic methods for certain cases of GH deficiency can provide the basis for a more accurate approach to therapeutic management.
§¤ÍÂȘ ÎÏÂȉȿ: ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÁÔÓ›‰ÈÔ GH, Pit-1, Prop-1, LHX3.
Key words: growth hormone deficiency (GHD), gene GH, Pit-1, Prop-1, LHX3.
∂ÈÛ·ÁˆÁ‹ ∏ ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growth hormone deficiency) Â›Ó·È Ì›· ‰È·Ù·Ú·¯‹ Ô˘ ÂÌÊ·Ó›˙ÂÙ·È ·ÁÎÔÛÌ›ˆ˜ ÛÂ Û˘¯ÓfiÙËÙ· 1:4000-10000
ÁÂÓÓ‹ÛÂȘ (1-3). ªfiÓÔ ÙÔ 20% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÔÊ›ÏÂÙ·È Û οÔÈÔ ÔÚÁ·ÓÈÎfi ·›ÙÈÔ (.¯. ÙÚ·‡Ì·, fiÁÎÔ ‹ Ïԛ̈ÍË), ÂÓÒ ÛÙȘ ˘fiÏÔȘ ÂÚÈÙÒÛÂȘ Ë ·ÈÙÈÔÏÔÁ›· Â›Ó·È ¿ÁÓˆÛÙË (Idiopathic) (4,5). ÕÚ·,
∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”, ∞ı‹Ó·
1st Pediatric Clinic, “P. & A. Kyriakou” Children’s Hospital, Athens
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¶·È‰È·ÙÚÈ΋ 2003;66:89-96
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˘ ‚·ıÌÔ‡ 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› Ó· Â›Ó·È ÌÂÌÔӈ̤ÓË (Isolated growth hormone deficiency, IGHD) ‹ Ó· Û˘Ó‰˘¿˙ÂÙ·È Ì ·Ó¿ÚÎÂÈ· Î·È ¿ÏÏˆÓ ˘ÔÊ˘ÛÈ·ÎÒÓ ÔÚÌÔÓÒÓ (Multiple pituitary hormone deficiency, MPHD). ¶ÚfiÛÊ·Ù˜ ÂÈÛÙËÌÔÓÈΤ˜ ÚfiÔ‰ÔÈ, fiˆ˜ Ë ·Ó¿Ï˘ÛË D¡∞, ¤¯Ô˘Ó Ô‰ËÁ‹ÛÂÈ ÛÙËÓ Ù·˘ÙÔÔ›ËÛË ÂÓfi˜ ·ÚÈıÌÔ‡ ÁÔÓȉ›ˆÓ, Ù· ÔÔ›· Â›Ó·È ·Â˘ı›·˜ ÂÌÏÂÎfiÌÂÓ· ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘ ˘fiÊ˘Û˘ Î·È ÙȘ ÂÍ·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 Û ˙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 ·fi ÙÔÓ Ô›ÛıÈÔ ÏÔ‚fi, Ô ÔÔ›Ô˜ ÚÔ¤Ú¯ÂÙ·È ·fi Ó¢ÚÈο ·ÙÙ·Ú· ÙÔ˘ ‰¿ÊÔ˘˜ Ù˘ 3˘ ÎÔÈÏ›·˜. OÈ ÔÚÌfiÓ˜ ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Û˘ÓÙ›ıÂÓÙ·È ·fi ¤ÓÙ ‰È·ÊÔÚÂÙÈΤ˜ ÔÌ¿‰Â˜ ÂÎÎÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (ۈ̷ÙÔÙÚfi·, ÁÔÓ·‰ÔÙÚfi·, Ï·ÎÙÔÙÚfi·, ı˘ÚÂÔÙÚfi· Î·È ÎÔÚÙÈÎÔÙÚfi·), ˘fi ÙËÓ Â›‰Ú·ÛË ˘Ôı·Ï·ÌÈÎÒÓ ÔÚÌÔÓÒÓ. ∏ ÂͤÏÈÍË ÙˆÓ Î˘ÙÙ¿ÚˆÓ ·˘ÙÒÓ Î·Ù¿ ÙËÓ ·Ú¯¤ÁÔÓË ÂÌÊ¿ÓÈÛ‹ ÙÔ˘˜ Û˘Ì‚·›ÓÂÈ Û ·˘ÛÙËÚ‹ ¯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· ·ÙÙ·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˘ (12Ë15Ë ÂÌ‚Ú˘˚΋ Ë̤ڷ), ÙÂÏÂ›Ù·È ˘fi ÙËÓ Â›‰Ú·ÛË ÔÚÈÛÌ¤ÓˆÓ ÚˆÙÂ˚ÓÒÓ (DNA-binding proteins), ÔÈ Ôԛ˜ 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 ‰ÔÌ‹ Ù˘ ÚˆÙ½Ó˘, ÙËÓ ÔÔ›· Έ‰ÈÎÔÔÈÔ‡Ó (‰ÔÌÈ΋
90
Paediatriki 2003;66:89-96
ÂÚÈÔ¯‹ ÙÔ˘ ÁÔÓȉ›Ô˘), ÂÚȤ¯Ô˘Ó Î·È ÙËÓ ÏËÚÔÊÔÚ›· ÁÈ· ÙË Ú‡ıÌÈÛË Ù˘ ›‰È·˜ ÙÔ˘˜ Ù˘ ¤ÎÊÚ·Û˘ (Ú˘ıÌÈÛÙÈ΋ ÂÚÈÔ¯‹). OÈ ·ÏÏËÏÔ˘¯›Â˜ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙË Ú‡ıÌÈÛË Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ ‰È·ÎÚ›ÓÔÓÙ·È Û ‰‡Ô ηÙËÁÔڛ˜: Ë Ì›· ÂÚÈÔ¯‹ Ô˘ ‚Ú›ÛÎÂÙ·È ÎÔÓÙ¿ 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˘Ó ηıÔÚÈṲ̂Ó˜ ı¤ÛÂȘ, ÛÙȘ Ôԛ˜ ÚÔÛ‰¤ÓÔÓÙ·È Û˘ÁÎÂÎÚÈ̤Ó˜ Ú˘ıÌÈÛÙÈΤ˜ ÚˆÙ½Ó˜, ÔÈ ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors), ÁÈ· ÙË Ú‡ıÌÈÛË Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘. ™ÙË ‰È·‰Èηۛ· ÌÂÙ·ÁÚ·Ê‹˜ ÙÔ˘ DNA Û RNA Û˘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 ÂÚÈÔ¯‹ 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 Ôԛ˜ 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›ÏÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÂÓfi˜ ÁÔÓȉ›Ô˘ (11,12). °ÔÓ›‰È· Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙÔ Û¯ËÌ·ÙÈÛÌfi Î·È ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡-˘fiÊ˘Û˘ ·) °ÔÓ›‰ÈÔ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (GHI): Έ‰ÈÎÔÔÈ› ÙËÓ ÂÓÙÔÏ‹ ÁÈ· ÙË Û‡ÓıÂÛË Ù˘ ˘ÔÊ˘Ûȷ΋˜ 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 hormone releasing hormone-GHRH) Î·È ‰ÈÂÁ›ÚÂÈ ÙËÓ ¤ÎÎÚÈÛË GH. Á) °ÔÓ›‰È· POUIF-1, Prop-1, LHX3, Hesx-1: Â›Ó·È “ÔÌÔÈÔÙÈο” ÁÔÓ›‰È· (homeobox genes), Ù· ÔÔ›· Έ‰ÈÎÔÔÈÔ‡Ó Ì›· ÔÈÎÔÁ¤ÓÂÈ· ·Ú·ÁfiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ (transcription factors), ÔÈ ÔÔ›ÔÈ ÂÓ¤¯ÔÓÙ·È ÛÙËÓ ÔÚÁ·ÓÔÁ¤ÓÂÛË ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘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‡ÓıÂÛË Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, Â›Ó·È ¤Ó· ·fi Ù· ÚÒÙ· ·ÓıÚÒÈÓ· ÁÔÓ›‰È· Ô˘ Ù·˘ÙÔÔÈ‹ıËÎ·Ó Î·È Â‰Ú¿˙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˘ ¯ÚfiÓÈ· ·fi ÙÔÓ John Phillips Î·È ¯·Ú·ÎÙËÚ›ÛÙËÎ·Ó ˆ˜ ·ÒÏÂȘ ÙÌ‹Ì·ÙÔ˜ (deletion) ÙÔ˘ ÁfiÓÔ˘ Ù˘ GH
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·91
¶·È‰È·ÙÚÈ΋ 2003;66:89-96
(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‡ÓıÂÛË Î·È ÙË ‰Ú·ÛÙËÚÈfiÙËÙ· Ù˘ GH Î·È ÔÈ Ôԛ˜ ÌÔÚ› Ó· Â›Ó·È ˘Â‡ı˘Ó˜ ÁÈ· ÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÎÏÈÓÈÎÔ‡˜ Ê·ÈÓfiÙ˘Ô˘˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. Œ¯Ô˘Ó ÂÚÈÁÚ¿ÊÂÈ Ù¤ÛÛÂÚȘ ÔÈÎÔÁÂÓ›˜ Ù‡ÔÈ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘. OÈ ‰‡Ô ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ÛˆÌ·ÙÈÎfi ¯·Ú·ÎÙ‹Ú· (IGHD πA Î·È πµ), ¤Ó·˜ Ì ÂÈÎÚ·ÙÔ‡ÓÙ· (IGHD II) Î·È Ô Ù¤Ù·ÚÙÔ˜ ÌÂ Ê˘ÏÔÛ‡Ó‰ÂÙÔ (IGHD IIπ) (16). ™ÙÔÓ ÚÒÙÔ Ù‡Ô π∞ Ù˘ ÌÂÌÔӈ̤Ó˘ ·Ó¿ÚÎÂÈ·˜ ·˘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¿ÍÂȘ Ô˘ ÚÔηÏÔ‡Ó ‰È·Ù·Ú·¯‹ ÙÔ˘ Ï·ÈÛ›Ô˘ ·Ó¿ÁÓˆÛ˘ (frame-shift mutation) ‹ Û ÌÂÙ·ÏÏ¿ÍÂȘ fiÔ˘ ˘¿Ú¯ÂÈ ÌÂÙ·ÙÚÔ‹ ÂÓfi˜ ·ÌÈÓÔͤԘ Û Έ‰ÈÎfiÓÈÔ Ï‹Í˘, ·ÓÂÚÌËÓ‡ÛÈÌË ÌÂÙ¿ÏÏ·ÍË (nonsense mutation) (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 ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (21) Î·È ¤¯Ô˘Ó Û˘Ó‹ıˆ˜ Ôχ ÎÔÓÙfi ·Ó¿ÛÙËÌ·, Ï‹ÚË ¤ÏÏÂÈ„Ë ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Î·È ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔÚ¤˜, fiÙ·Ó ÙÔ˘˜ ¯ÔÚËÁÂ›Ù·È GH, ·Ú¿ÁÔ˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ·˘Ù‹˜. ™ÙÔÓ Ù‡Ô IGHD πµ, ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓ›‰ÈÔ˘ GH ·ÊÔÚÔ‡Ó Û ˘ÔηٷÛÙ¿ÛÂȘ ‚¿ÛÂˆÓ Ô˘ ÂËÚ¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ Î·È Ù˘ Â·Ó·Û˘ÁÎfiÏÏËÛ˘ (splicing) ÙÔ˘ RNA (16). OÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹ÎÔ˘Ó Û ·˘ÙfiÓ ÙÔÓ Ù‡Ô ¤¯Ô˘Ó ¯·ÌËϤ˜ ÙÈ̤˜ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ηϋ ·ÓÙ·fiÎÚÈÛË Û 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›‰ÈÔ Ù˘ 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›ˆÓ Î·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˘Ó ÛÙÔÓ Ù‡Ô IGHD II, ¤¯Ô˘Ó Î·È ·˘ÙÔ› ÎÔÓÙfi ·Ó¿ÛÙËÌ·, ¯·ÌËϤ˜ ÙÈ̤˜ GH, ηϋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· ˘ÔηٿÛÙ·Û˘ Î·È ‰ÂÓ ·Ó·Ù‡ÛÛÔ˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ GH. ∆¤ÏÔ˜, ÔÈ ·ÛıÂÓ›˜ Ô˘ ·Ó‹ÎÔ˘Ó ÛÙÔÓ Ù‡Ô IGHD III ·ÚÔ˘ÛÈ¿˙Ô˘Ó ¤ÏÏÂÈ„Ë Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘, ÂÓÒ ÌÂÚÈÎÔ› ·fi ·˘ÙÔ‡˜ ¤¯Ô˘Ó Î·È ·Á·ÌÌ·ÛÊ·ÈÚÈÓ·ÈÌ›· (25). OÈ ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘
Paediatriki 2003;66:89-96
˘Ê›ÛÙ·ÓÙ·È ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH Û ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ, ‰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· ۈ̷ÙÔÙÚfi· ·ÙÙ·Ú·, ÙÔ ˘Ôı·Ï·ÌÈÎfi ÂÚ¤ıÈÛÌ· ÁÈ· ÙÔÓ ·Ú¿ÁÔÓÙ· ¤ÎÏ˘Û˘ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (Growth hormone releasing hormone, GHRH) ·Ó·ÁÓˆÚ›˙ÂÙ·È Î·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 GÚˆÙÂ˚ÓÒÓ (G-protein coupled receptors). ∆Ô Û‡ÛÙËÌ· ÙˆÓ G-ÚˆÙÂ˚ÓÒÓ ·ÔÙÂÏ› ¤Ó· ‰È¿ÌÂÛÔ ·Ú¿ÁÔÓÙ· 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 1992 Î·È Â‰Ú¿˙ÂÙ·È ÛÙÔ 7Ú ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ (29). O GHRH ˘Ô‰Ô¯¤·˜ ¤¯ÂÈ ¤Ó· ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ ΢ÙÙ¿ÚˆÓ Ù˘ ˘fiÊ˘Û˘ Î·È Ú˘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 ÌÂÙ·ÙÚÔ‹ ÂÓfi˜ ·ÌÈÓÔͤԘ Û Έ‰ÈÎfiÓÈÔ Ï‹Í˘, ·ÓÂÚÌËÓ‡ÛÈÌË ÌÂÙ¿ÏÏ·ÍË (nonsense mutation) ‹ ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ ·ÊÔÚÔ‡Ó Û ˘ÔηٷÛÙ¿ÛÂȘ ‚¿ÛÂˆÓ Î·È ÂËÚ¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ·ÔÎÔ‹˜ Î·È Ù˘ Â·Ó·Û˘ÁÎfiÏÏËÛ˘ (splicing) ÙÔ˘ RNA (splice site mutation) (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 ˘ÔÏ·Û›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÂÓÒ ¤¯Ô˘Ó ηϋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂڷ›· ˘ÔηٿÛÙ·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¿ ÙÔ 1988 (39) Î·È ‚Ú¤ıËΠfiÙÈ ÂÓÙÔ›˙ÂÙ·È ÛÙÔ 3ƒ11 ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ (40). ∏ Pit (1) ÚˆÙ½ÓË ·ÓȯÓ‡ÂÙ·È ÛÙÔÓ ˘Ú‹Ó· ÙÚÈÒÓ Î˘ÙÙ·ÚÈÎÒÓ ÛÂÈÚÒÓ ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÙˆÓ ÛˆÌ·ÙÔÙÚfiˆÓ, ÙˆÓ Ï·ÎÙÔÙÚfiˆÓ Î·È ÙˆÓ ı˘ÚÂÔÂȉÔÙÚfiˆÓ (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· ÙË ÌÂÙ¤ÂÈÙ· ‰È¤ÁÂÚÛ‹ ÙÔ˘˜.
91
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·92
¶·È‰È·ÙÚÈ΋ 2003;66:89-96
ªÂÙ·ÏÏ¿ÍÂȘ, ÂÔ̤ӈ˜, ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ ÚÔηÏÔ‡Ó Û˘Ó‰˘·Ṳ̂ÓË ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘ ÁÈ· ·˘ÍËÙÈ΋ ÔÚÌfiÓË (GH), ÚÔÏ·ÎÙ›ÓË (PRL) Î·È ı˘ÚÂÔÙÚfiÔ ÔÚÌfiÓË (TSH). ∏ ÚÒÙË ·ÓıÚÒÈÓË ÌÂÙ¿ÏÏ·ÍË ÛÙÔ POUIF-1 ÁÔÓ›‰ÈÔ ·Ó·Ê¤ÚıËΠÙÔ 1992, 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 ÌÂÙ¿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 Ì ÙÔÓ ÂÈÎÚ·ÙÔ‡ÓÙ· ¯·Ú·ÎÙ‹Ú·, ·Ó¿ÏÔÁ· Ì ÙË ı¤ÛË Ù˘ 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 ÌÂÙ·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· ‚¿ÛÂˆÓ (deletion) (44). O Ê·ÈÓfiÙ˘Ô˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ POUIF-1 ÔÈΛÏÏÂÈ Î·È ‰ÂÓ ¤¯ÂÈ Û¯¤ÛË Ì ÙÔ Â›‰Ô˜ ÙˆÓ ÌÂÙ·ÏϿ͈Ó, Ô‡Ù Ì ÙÔÓ ÙÚfiÔ Ô˘ ·˘Ù¤˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤¯Ô˘Ó ¤ÏÏÂÈ„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˘, ÂÓÒ Û ¿ÏÏÔ˘˜ ·ÛıÂÓ›˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË 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˘ÚÂÔÂȉÔÙÚfiˆÓ ΢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) Î·È ıˆÚÂ›Ù·È Ô˘ÛÈ·ÛÙÈÎfi ÁÈ· ÙËÓ ¤ÎÊÚ·ÛË Ù˘ Pit ÚˆÙ½Ó˘ 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¿ÚÎÂÈ· Ù˘ ÂÌ‚Ú˘˚΋˜ ·Ó¿Ù˘Í˘ Ù˘ ˘fiÊ˘Û˘ Î·È ÚÔËÁÂ›Ù·È ¿ÓÙÔÙ Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ Pit ÁÔÓ›‰ÈÔ˘. °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 ÌÂÙ¿ÏÏ·ÍË ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ ·Ó·Ê¤ÚıËΠÙÔ 1998 Î·È ·fi ÙfiÙ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÂÙ¿ ·ÎfiÌ· ÌÂÙ·ÏÏ¿ÍÂȘ (8). ŸÏ˜ ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú· Î·È ÔÈ ÂÚÈÛÛfiÙÂÚ˜ ·ÊÔÚÔ‡Ó Û ÌÈÎÚ¿ ÂÏÏ›ÌÌ·Ù· ‚¿ÛÂˆÓ Ô˘ ÚÔη-
92
Paediatriki 2003;66:89-96
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 ÔÏ˘ÂÙȉÈ΋ ·Ï˘Û›‰· ηٿ ÙË ÌÂÙ¿ÊÚ·ÛË-·ÚÂÚÌËÓ‡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¿ÁÓˆÛ˘ ÂÍ·ÚÙ¿Ù·È ·fi ÙË ‚·Ú‡ÙËÙ· ÙˆÓ Û˘ÌÙˆÌ¿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 ·fi ÛÔ‚·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 ÌÂÙ·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›˜ Ì ÌÂÙ·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˘ ÔÚÌfiÓ˘ (ACTH) (8). ™ÙÔ˘˜ ·ÛıÂÓ›˜, ÂÔ̤ӈ˜, Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ ‰ÂÓ Â›Ó·È ÂÊÈÎÙ‹ Ë ¤ÎÊÚ·ÛË ÙÔ˘ Pit1 ·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 ÊÏÔÈÔÙÚfiÔ ÔÚÌfiÓË (ACTH), Ì ·ÔÙ¤ÏÂÛÌ· Ó· ··ÈÙÂ›Ù·È ıÂڷ›· ˘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 “ÔÌÔÈÔÂÚÈÔ¯‹” (homeodomain-containing tran-scription factor) Î·È ÂÌÊ·Ó›˙ÂÙ·È Ôχ ÓˆÚ›˜, ηٿ ÙËÓ ÂÔ¯‹ Ù˘ ÔÚÁ·ÓÔÁ¤ÓÂÛ˘ Ù˘ ˘fiÊ˘Û˘ ·fi ÙÔ ı‡Ï·ÎÔ ÙÔ˘ Rathke. O ·Ú¿ÁˆÓ L∏Ã3 ‰Ú· Û˘ÓÂÚÁ·ÙÈο Ì ÙÔ 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‡ÛÈ̘ ÌÂÙ·ÏÏ¿ÍÂȘ (missence) ‹ ·ÒÏÂȘ ‚¿ÛÂˆÓ (deletion), ÔÈ Ôԛ˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú·. OÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÛÔ‚·Ú‹ ηı˘ÛÙ¤ÚËÛË ÛÙËÓ ·Ó¿Ù˘ÍË Î·È ¤¯Ô˘Ó ÎÔÓÙfi Î·È ¯ÔÓ‰Úfi ·˘¯¤Ó· Ì ÂÚÈÔÚÈṲ̂ÓË ÛÙÚÔÊ‹ Ù˘ ÎÂÊ·Ï‹˜. ∂›Û˘, ÂÌÊ·Ó›˙Ô˘Ó ˘ÔÏ·Û›· Ù˘
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·93
¶·È‰È·ÙÚÈ΋ 2003;66:89-96
˘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˘, ÏËÓ Ù˘ 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· (homeobox genes) Ù˘ ˘fiÊ˘Û˘ Ô˘ ÂÎÊÚ¿˙ÂÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÚÒÙˆÓ ÛÙ·‰›ˆÓ ·Ó¿Ù˘Í˘ Ù˘ ˘fiÊ˘Û˘ Î·È ‚Ú›ÛÎÂÙ·È ÛÙÔÓ ¿ÓıÚˆÔ ÛÙÔ ¯ÚˆÌfiۈ̷ 3 (3p21.2) (67,68). ∏ ·Ô˘Û›· Ù˘ Hesx-1 ÚˆÙ½Ó˘ ÛÙ· ÔÓÙ›ÎÈ· ÈÛÙ‡ÂÙ·È fiÙÈ ÚÔηÏ› ‰È·Ù·Ú·¯¤˜ ÛÙÔ ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ· Î·È ‰˘ÛÏ·Û›· Ù˘ ˘fiÊ˘Û˘ (69). ¶Ôχ ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ Hesx1 ·ÓıÚÒÈÓÔ ÁÔÓ›‰ÈÔ ¤¯ÂÈ ·Ó·ÊÂÚı› ÚfiÛÊ·Ù·, ÔÈ Ôԛ˜ ÎÏËÚÔÓÔÌÔ‡ÓÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ‹ Ì ÂÈÎÚ·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¢ڛÛÎÔÓÙ·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›· ˘ÔηٿÛÙ·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 ‰ÈfiÙÈ ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔÚ¤˜ Ë ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÂÊ·ÚÌfi˙ÂÙ·È Û ηıÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ Î·È ÌÂ Û˘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΋ ÂÈÎfiÓ· Î·È ÙȘ ÁÓˆÛÙ¤˜ ‰ÔÎÈ̷ۛ˜ ÚfiÎÏËÛ˘. ∂Í¿ÏÏÔ˘, Ë ·Ó·Ï˘ÙÈ΋ ÂͤٷÛË DNA Â›Ó·È Ì›· ¯ÚÔÓÔ‚fiÚ· Î·È ·ÎÚÈ‚‹ ̤ıÔ‰Ô˜, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌËÓ ÌÔÚ›, 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· ˘fiÊ˘Û˘ (CPHD) ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ GH ÈÛÙ‡ÂÙ·È fiÙÈ Êı¿ÓÂÈ ÂÚ›Ô˘ ÛÙÔ 10% ÙˆÓ
Paediatriki 2003;66:89-96
·ÛıÂÓÒÓ Ì ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ˘fiÊ˘Û˘ (IGHD) (6,17,70). ∞ÓÙ›ÛÙÔȯ·, Ë Û˘¯ÓfiÙËÙ· ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ GHRHR ÁÔÓ›‰ÈÔ Ê·›ÓÂÙ·È Ó· Â›Ó·È Ôχ ÌÈÎÚfiÙÂÚË. ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ì ÌÂÌÔӈ̤ÓË ·Ó¿ÚÎÂÈ· ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (IGHD) ÂÍ·ÎÔÏÔ˘ı› Ó· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ˆ˜ ȉÈÔ·ı‹˜. ∆· ÂÚÈÔÚÈṲ̂ӷ Û˘ÌÂÚ¿ÛÌ·Ù· ÙˆÓ ‰È·ÊfiÚˆÓ ÌÂÏÂÙÒÓ 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‡ÂÙ·È fiÙÈ ÛÙË ÏÂÙ‹ ÂÈÎÔÈÓˆÓ›· ˘Ôı·Ï¿ÌÔ˘-˘fiÊ˘Û˘ ÂÌϤÎÔÓÙ·È ·Ú¿ÁÔÓÙ˜ ÏÈÁfiÙÂÚÔ ‰È¢ÎÚÈÓÈṲ̂ÓÔÈ ·fi ÂΛÓÔ˘˜ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙË ‰È·ÊÔÚÔÔ›ËÛË Ù˘ ˘fiÊ˘Û˘ (6). ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, Ë Ù·˘ÙÔÔ›ËÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ (Transcription factors), ÔÈ ÔÔ›ÔÈ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·Ó¿Ù˘ÍË Î·È ÙË ‰È·ÊÔÚÔÔ›ËÛË Ù˘ ˘fiÊ˘Û˘, Ì¿˜ ‚ÔËı¿ Ó· ηٷÓÔ‹ÛÔ˘Ì ÙËÓ ·ıÔÁ¤ÓÂÛË ÙˆÓ ‰È·ÊÔÚÂÙÈÎÒÓ Ù‡ˆÓ ÔÏÏ·Ï‹˜ ·Ó¿ÚÎÂÈ·˜ ˘fiÊ˘Û˘ (CPHD). ™‡Ìʈӷ Ì 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 Î·È ÁÔÓ·‰ÔÙÚÔÈÓÒÓ ¤¯Ô˘Ó ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Prop-1 ÁÔÓ›‰ÈÔ. OÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Hesx-1 ÁÔÓ›‰ÈÔ, Ô˘ ÂÎÊÚ¿˙ÔÓÙ·È ÓˆÚ›˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÌÊ¿ÓÈÛ˘ Î·È ‰È·ÊÔÚÔÔ›ËÛ˘ Ù˘ ˘fiÊ˘Û˘, Â›Ó·È Ôχ ÂÚÈÔÚÈṲ̂Ó˜ 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· ÙˆÓ LHX3 ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔÓ ¿ÓıÚˆÔ, ÏfiÁˆ ÙÔ˘ ÂÚÈÔÚÈṲ̂ÓÔ˘ ·ÚÈıÌÔ‡ ÂÚÈÙÒÛˆÓ. ™˘ÌÂÚ¿ÛÌ·Ù· ∏ ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˘ÔÊ˘Ûȷ΋ ·Ó¿ÚÎÂÈ· ÌÔÚ› Ó· ·Ú¿Û¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· 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·ÎÚÔÚfiıÂÛ̘ Û˘Ó¤ÂȤ˜ ÙÔ˘. ∂›Û˘, Ë ·Ó·Î¿Ï˘„Ë ÙÔ˘ ›‰Ô˘˜ ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÙˆÓ ÁÔÓȉ›ˆÓ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙÔÓ Û¯ËÌ·ÙÈÛÌfi Î·È ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÚfiÛıÈÔ˘ ÏÔ‚Ô‡ Ù˘ ˘fiÊ˘Û˘, ÌÔÚ› Ó· ‰ÒÛÂÈ ÔχÙÈ̘ ÏËÚÔÊÔڛ˜ Û¯ÂÙÈο Ì ÙÔÓ ÙÚfiÔ ÎÏËÚÔÓÔÌÈÎfiÙËÙ·˜ ÙˆÓ ‰È·ÊfiÚˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘, ÙËÓ ÚfiÁÓˆÛ‹ 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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‰È¿ÁÓˆÛË (ȉÈÔ·ı‹˜) ·Ó¿ÚÎÂÈ· Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ıˆÚËı› Ì›· ‰È·ÁÓˆÛÙÈ΋ ÔÓÙfiÙËÙ· ÙÔ˘ ·ÚÂÏıfiÓÙÔ˜.
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novel homeobox gene Hesx1. J Biol Chem 1995;270:38693875. 68. Hermesz E, Mackem S, Mahon KA. Rpx: a novel anteriorrestricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke’s pouch of the mouse embryo. Development 1996;122:41-52. 69. Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Martensson IL et al. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet 1998;19:125133. 70. Mullis PE, Akinci A, Kanaka C, Eble A, Brook CG. Prevalence of human growth hormone-1 gene deletions among patients with isolated growth hormone deficiency from different populations. Pediatr Res 1992;31:532-534. HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 29-07-2002 HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 31-01-2003 ¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ª·Ú›·-™Ù¤ÏÏ· §·Ú›Ô˘ π¤ÚˆÓÔ˜ 13, ∆.∫. 116 34, ¶·ÁÎÚ¿ÙÈ, ∞ı‹Ó·
¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›· ∞ÌÊÔÙÂÚfiÏ¢ÚÔÈ ÏÂÈÔ΢ÛÙÈÎÔ› ÓÂÊÚÔ› - ¤Ó· ·Û˘Ó‹ıÈÛÙÔ ÂÚÈÛÙ·ÙÈÎfi1 ∏ ÏÂÈÔ΢ÛÙÈ΋ ‰˘ÛÏ·Û›· ÙˆÓ ÓÂÊÚÒÓ Â›Ó·È Û¯ÂÙÈο Û˘¯Ó‹ ·ÈÙ›· ÓÂÊÚÈ΋˜ Ì¿˙·˜ ÛÙ· ÓÂÔÁÓ¿, ¤¯ÂÈ Î·Ï‹ ÚfiÁÓˆÛË Î·È Û˘Ó‹ıˆ˜ ‰È·ÈÛÙÒÓÂÙ·È ÛÙÔÓ ¤Ó· ÓÂÊÚfi. ∂›Ó·È ·ÁÓÒÛÙÔ˘ ·ÈÙÈÔÏÔÁ›·˜ Î·È Û ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ÙÔÓ ÂÈÎÚ·ÙÔ‡ÓÙ· ۈ̷ÙÈÎfi ¯·Ú·ÎÙ‹Ú·. ™Â ÔÛÔÛÙfi 10-25%, Ô ˘ÁÈ‹˜ ÓÂÊÚfi˜ ·ÚÔ˘ÛÈ¿˙ÂÈ Î˘ÛÙÂÔÔ˘ÚËÙËÚÈ΋ ·ÏÈÓ‰ÚfiÌËÛË Î·È, 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˘ ÂÚÈÁÚ¿ÊÂÙ·È, Ë ·ÛıÂÓ‹˜ Ì ·ÌÊÔÙÂÚfiÏ¢ÚÔ˘˜ ÏÂÈÔ΢ÛÙÈÎÔ‡˜ ÓÂÊÚÔ‡˜ ·ÚÔ˘Û›·˙ ΢ÛÙÈ΋ ‰˘ÛÏ·Û›· ÌfiÓÔ ÛÙÔ ¿Óˆ ÙÌ‹Ì· ÙÔ˘ ‰ÂÍÈÔ‡ ÓÂÊÚÔ‡ Ô˘ ‰È·ÈÛÙÒıËÎÂ Î·È ‰ÈÏ·ÛÈ·ÛÌfi ÙÔ˘ ˘ÂÏÔÎ·Ï˘ÎÈÎÔ‡ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜. ∏ ·ÛıÂÓ‹˜ ‰ÂÓ ·ÚÔ˘-
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1 Agrawal L, Millard ML, Fairhurst J, Gilbert RD Bilateral multicystic kidneys - an unusual case Pediatr Nephrol 2002;17:964-965
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REVIEW ARTICLE
™‡Ó‰ÚÔÌ· ÙÔÍÈ΋˜ ηٷÏËÍ›·˜ ÛÙ· ·È‰È¿ °. ™È‰¤ÚË, ∞. µ·ÛÈÏfiÔ˘ÏÔ˜
Toxic shock syndromes G. Sideri, A. Vassilopoulos
¶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 Â͈ÙÔ͛Ә 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, Ë ‰Ú¿ÛË ÙˆÓ ÔÔ›ˆÓ ÚÔηÏ› ÙȘ Û˘ÛÙËÌ·ÙÈΤ˜ ·ıÔÊ˘ÛÈÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ (˘fiÙ·ÛË, ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·). ∆Ô Û‡Ó‰ÚÔÌÔ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ÎÏÈÓÈο ·fi ˘ÚÂÙfi, ‰È¿¯˘ÙÔ ÎËÏȉ҉˜ ÂÍ¿ÓıËÌ·, ˘fiÙ·ÛË Î·È ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ·. °È· ÙËÓ ÂÈÙ˘¯‹ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ·›˙ÂÈ Ë ·ÓÙÈÌÈÎÚԂȷ΋ ·ÁˆÁ‹, ·ÏÏ¿ ΢ڛˆ˜ Ë ¤ÁηÈÚË ·ÓÙÈÌÂÙÒÈÛË Ù˘ ΢ÎÏÔÊÔÚÈ΋˜ ηٷÏËÍ›·˜, Ë ‰È·Ù‹ÚËÛË ÈηÓÔÔÈËÙÈ΋˜ ηډȷ΋˜ ·ÚÔ¯‹˜ (¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ, ÈÓÔÙÚfiˆÓ) Î·È Ë ·ÔηٿÛÙ·ÛË ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ÔÌÔÈfiÛÙ·Û˘.
Abstract: The toxic shock syndrome (TSS) is an uncommon but severe clinical problem in children. The pathological conditions that precipitate this syndrome are acute multisystem disorders, associated with infection/colonization by strains of Staphylococcus aureus or Streptococcus pyogenes (and rarely other streptococcal species) which produce exotoxins capable of acting as superantigens. Although clinically distinct, staphylococcal and streptococcal types of TSS are believed to share this common pathogenetic mechanism. Superantigen activity results in a massive release of proinflammatory cytokines which cause multisystem disorders. Clinically the syndrome is characterized by fever, hypotension, erythroderma, and multisystem failure. The successful management of TSS is based on the administration of appropriate antibiotic agents, but primarily on the timely management of circulatory shock (fluid balance, use of inotropic agents) and the conservation of adequate cardiac output).
§¤ÍÂȘ ÎÏÂȉȿ: Û‡Ó‰ÚÔÌ· ÙÔÍÈ΋˜ ηٷÏËÍ›·˜, ÛÙÚÂÙÔÎÔÎÎÈÎfi ÙÔÍÈÎfi Û‡Ó‰ÚÔÌÔ, ÛÙ·Ê˘ÏÔÎÔÎÎÈÎfi ÙÔÍÈÎfi Û‡Ó‰ÚÔÌÔ, ÙÔÍ›ÓË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ù˘ ÙÔÍÈ΋˜ ηٷÏËÍ›·˜.
Key words: toxic shock syndrome, streptococcal toxic shock syndrome, staphylococcal toxic shock syndrome, toxic shock syndrome toxin-1.
™˘ÓÙÔÌÔÁڷʛ˜ TSS TSST-1 TNF IL-1
Toxic shock syndrome Toxic shock syndrome toxin-1 Tumor necrosis factor Interleukin 1
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TCR CPK ¢∂™ ∞ª¶
T-cell receptor ∫Ú·ÙÈÓÈ΋ ʈÛʈÎÈÓ¿ÛË ¢ÈÎÙ˘ÔÂÓ‰ÔıËÏÈ·Îfi Û‡ÛÙËÌ· ∞ÈÌÔÂÙ¿ÏÈ·
Paediatric Intensive Care Unit, “P. & A. Kyriakou” Children’s Hospital, Athens
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∂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¯ÔÓÙÔ˜ ·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·È ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙˆÓ ÙÔÍÈÎÒÓ ÂÍ·ÓıËÌ·ÙÈÎÒÓ 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‰ÚÔÌÔ Stevens-Johnson). ∂ΉËÏÒÓÔÓÙ·È Ôͤˆ˜ Ì ‚·ÚÈ¿ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È Û˘Óԉ‡ÔÓÙ·È ·fi Ïԛ̈ÍË/·ÔÈÎÈÛÌfi Ì ÛÙÂϤ¯Ë Staphylococcus 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· ÚÒÙË ÊÔÚ¿ ÙÔ 1978, ÂÓÒ ÙÔ ÛÙÚÂÙÔÎÔÎÎÈÎfi TSS ÙÔ 1989. ¶·Ú¿ ÙÔÓ ÎÏÈÓÈÎfi ‰È·¯ˆÚÈÛÌfi, Ô ·ıÔÁÂÓÂÙÈÎfi˜ Ì˯·ÓÈÛÌfi˜ Â›Ó·È Ô ›‰ÈÔ˜. ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· ÙÂÏÂ˘Ù·›· ‰Â‰Ô̤ӷ Û fi,ÙÈ ·ÊÔÚ¿ ÛÙËÓ ·ıÔÁ¤ÓÂÈ·, ÙȘ ·ıÔÊ˘ÛÈÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜, Ù· ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹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˜. ªfiÓÔ ÙÔ 50% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÙÔ˘ staph-TSS ÚÔηÏÂ›Ù·È Î¿Ùˆ ·fi ·˘Ù¤˜ ÙȘ Û˘Óı‹Î˜ (1), ÂÓÒ ÔÈ ˘fiÏÔȘ ÂÚÈÙÒÛÂȘ Û˘Ó‰˘¿˙ÔÓÙ·È Ì ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ, ÂÁη‡Ì·Ù·, ÙÔÎÂÙÔ‡˜, ÏÔÈÌÒÍÂȘ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ Î·È ÏÔÈÌÒÍÂȘ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ (2). °È· ¿ÁÓˆÛÙÔ˘˜ ÏfiÁÔ˘˜, ÙÔ staph-TSS Â›Ó·È Û¿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 ·ÓÙÈÛÒÌ·Ù·. ¶·ıÔÁ¤ÓÂÈ· °È· ÙËÓ ·Ó¿Ù˘ÍË ÙÔ˘ staph-TSS ÚÔ··ÈÙÂ›Ù·È ·ÔÈÎÈÛÌfi˜ Ì Û٤ϯԘ ÙÔ˘ S. aureus, ÙÔ ÔÔ›Ô ·Ú¿ÁÂÈ ÙÔÍ›ÓË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÙÔÍÈ΋˜ ηٷÏËÍ›·˜ (TSST-1) ‹, ÏÈÁfiÙÂÚÔ Û˘¯Ó¿, Ì›· ‹ ÂÚÈÛÛfiÙÂÚ˜ 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¯ÂÙÈο ÚfiÛÊ·Ù· ·Ó·ÁÓˆÚÈṲ̂ÓË ÔÌ¿‰· ·ÓÙÈÁÔÓÈÎÒÓ ÌÔÚ›ˆÓ, Ù· ÔÔ›· Ê·›ÓÂÙ·È fiÙÈ ÚÔηÏÔ‡Ó ‹ ÚÔ¿-
98
Paediatriki 2003;66:97-103
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‰ÂÛ˘ 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 ÙËÓ ÈηÓfiÙËÙ· 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΋ ·ÂÏ¢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. aureus ÁÈ· Ó· ÚÔηϤÛÂÈ staph-TSS, ·Ó Ï¿‚Ô˘Ì ˘’ fi„ÈÓ fiÙÈ Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ·ÓıÚÒˆÓ Ô˘ Â›Ó·È ·ÔÈÎÈṲ̂ÓÔÈ ‹ ÓÔÛÔ‡Ó ·fi ·˘Ù¿ Ù· ÛÙÂϤ¯Ë ‰ÂÓ ·Ó·Ù‡ÛÛÔ˘Ó ÔÙ¤ Ïԛ̈ÍË ÌfiÓÔ ·fi ÙË ÌÂÛÔÏ¿‚ËÛË Ù˘ ÙÔ͛Ӣ. °È· ·Ú¿‰ÂÈÁÌ·, Ô S. aureus Ô˘ ÌÂٷʤÚÂÈ TSST-1 ÁÔÓ›‰ÈÔ, ·ÚÔ˘ÛÈ¿˙ÂÙ·È Û ÔÛÔÛÙfi 1-5% ÛÙȘ ÎÔÏÈΤ˜ ηÏÏȤÚÁÂȘ ÙˆÓ Á˘Ó·ÈÎÒÓ Î·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 ·ÔÈÎÈṲ̂ÓÔ Ì S. aureus ÈηÓfi Ó· ·Ú¿ÁÂÈ TSST-1 (5). ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ì›· ÛÂÈÚ¿ ·Ú·ÁfiÓÙˆÓ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙÔ˘ staph-TSS. ∆¤ÙÔÈÔÈ ·Ú¿ÁÔÓÙ˜, ¤Ú·Ó ÙÔ˘ ·ÔÈÎÈÛÌÔ‡ ‹ Ù˘ Ïԛ̈͢ ·fi ¯Ú˘Û›˙ÔÓÙ· ÛÙ·Ê˘ÏfiÎÔÎÎÔ Ô˘ ·Ú¿ÁÂÈ ÙÔ͛Ә, Â›Ó·È ÔÈ ·ÂÚfi‚Ș Û˘Óı‹Î˜, ÙÔ Ô˘‰¤ÙÂÚÔ pH, Ë ıÂÚÌÔÎÚ·Û›· 37-40ÔC, Ë ¤ÏÏÂÈ„Ë Mg, Ë ÂÚ›ÛÛÂÈ· ÚˆÙÂ˚ÓÒÓ Î·È, Ù¤ÏÔ˜, Ë ·Ô˘Û›· ÚÔÛٷ٢ÙÈÎÔ‡ ·ÓÙÈÛÒÌ·ÙÔ˜ ¤Ó·ÓÙÈ Ù˘ ÂȉÈ΋˜ ÙÔ͛Ӣ. ∏ ·Ô˘Û›· ·ÓÔÛ›·˜ ÔÊ›ÏÂÙ·È ÛÙËÓ ¤ÏÏÂÈ„Ë ÚÔËÁÔ‡ÌÂÓ˘ ¤ÎıÂÛ˘ ‹ ÛÙËÓ ·‰˘Ó·Ì›· ·Ú·ÁˆÁ‹˜ ·˘ÙÒÓ ÙˆÓ ·ÓÙÈۈ̿وÓ. 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), ÌfiÓÔ ÙÔ 30% ˘ÁÈÒÓ ·È‰ÈÒÓ ËÏÈΛ·˜ 1-2 ÂÙÒÓ Â›¯Â ÚÔÛٷ٢ÙÈÎÔ‡˜ Ù›ÙÏÔ˘˜ ·ÓÙÈÛˆÌ¿ÙˆÓ (>1:100) ¤Ó·ÓÙÈ Ù˘ TSST-1. ∞ÓÙ›ıÂÙ·, Û‡Ìʈӷ Ì ÙË ÌÂϤÙË ÙˆÓ Notermans Î·È Û˘Ó (17), ÙÔ ·ÓÙ›ÛÙÔÈ¯Ô ÔÛÔÛÙfi ·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¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 9 ÌËÓÒÓ. ∆Ô 1980, ÔÈ Schlievert Î·È Û˘Ó (15) Ù·˘ÙÔÔ›ËÛ·Ó Ì›· Â͈ÙÔÍ›ÓË Ô˘ ·›˙ÂÈ ÚˆÙ‡ÔÓÙ· ÚfiÏÔ ÛÙËÓ ·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˘
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·99
¶·È‰È·ÙÚÈ΋ 2003;66:97-103
Ù‡Ô˘ Î·È ÚÔηÏ› ηٷÛÙÔÏ‹ Ù˘ Û‡ÓıÂÛ˘ ·ÓÔÛÔÛÊ·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›· ÂÁηٿÛÙ·ÛË ˘fiÙ·Û˘, Ô˘ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÈÛÙÈ΋ 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‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ) ·Ú·ÁfiÓÙˆÓ Ô˘ Ô‰ËÁÔ‡Ó Û ÂÎÙÂٷ̤ÓË ÂÓ‰ÔıËÏȷ΋ ‚Ï¿‚Ë ÌÂ Û˘Ó¤ÂÈ·: i) ÂÏ¿ÙÙˆÛË ÙÔ˘ ÙfiÓÔ˘ ÙˆÓ ·ÁÁ›ˆÓ (Ì›ˆÛË ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ·ÁÁÂÈ·ÎÒÓ ·ÓÙÈÛÙ¿ÛˆÓ) Î·È Ï›ÌÓ·ÛË ÙÔ˘ ·›Ì·ÙÔ˜ ÛÙ· ÂÚÈÊÂÚÈο ·ÁÁ›· Î·È ii) ·˘ÍË̤ÓË ‰È·ÂÚ·ÙfiÙËÙ· Ù˘ ΢ÙÙ·ÚÈ΋˜ ÌÂÌ‚Ú¿Ó˘ Î·È ‰È·Ê˘Á‹ ˘ÁÚÒÓ Ì ˘„ËÏ‹ ÂÚÈÂÎÙÈÎfiÙËÙ· ۠χΈ̷ ·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‚·ÛÙÒÓ ÛÙ· ·ÙÙ·Ú· Î·È ii) Ù˘ ÈÛÙÈ΋˜ ÈÛ¯·ÈÌ›·˜, Ô˘ ·Ú¯Èο ÔÊ›ÏÂÙ·È ÛÙÔÓ ¯·ÌËÏfi ÙfiÓÔ ÙˆÓ ·ÁÁ›ˆÓ Î·È ÛÙÔ ÂÎÙÂٷ̤ÓÔ ‰È¿ÌÂÛÔ Ô›‰ËÌ· Ô˘ Û˘ÌȤ˙ÂÈ Î·È ÚÔηÏ› ‰˘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·È Û˘¯Ó¿ ÈÔ ÂÒ‰˘ÓˆÓ Î·È ·Ú·ÙÂÙ·Ì¤ÓˆÓ ÂΉËÏÒÛÂˆÓ ÙÔ˘ TSS. ¶Èı·Ófiٷٷ, Â›Ó·È ·ÔÙ¤ÏÂÛÌ· Ù˘ ‰Ú¿Û˘ ÙˆÓ IL-1 Î·È TNF. ∫·È ÔÈ ‰‡Ô ÚÔηÏÔ‡Ó ÚˆÙÂfiÏ˘ÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÚÔÛÙ·ÁÏ·Ó‰›Ó˘ ∂2, Ô˘ Â›Ó·È ÈÛ¯˘Úfi˜ ‰ÈÂÁ¤ÚÙ˘ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ fiÓÔ˘. ‚. ∏ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ÙÔ˘ TSS ÂΉËÏÒÓÂÙ·È Ì ÔÓÔΤʷÏÔ, Û‡Á¯˘ÛË, ·ÔÚÔÛ·Ó·ÙÔÏÈÛÌfi Î·È Û·ÛÌÔ‡˜ Î·È ÔÊ›ÏÂÙ·È ÛÙÔ ÂÎÙÂٷ̤ÓÔ ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ·. Á. ∏ ÂÎÎÚÈÙÈ΋, Û˘¯Ó¿ ¿ÊıÔÓË, ‰È¿ÚÚÔÈ· ˘¿Ú¯ÂÈ Û¯Â‰fiÓ Û fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜. ∂ÌÊ·Ó›˙ÂÙ·È Ì 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¢ÚÈÙÈ΋ Û˘ÏÏÔÁ‹. Â. ∏ ÔÍ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Â›Ó·È Û˘Ó‹ı˘ ÂΉ‹ÏˆÛË Î·È Â›Ó·È ÓÂÊÚÈ΋˜ Î·È ÚÔ-ÓÂÊÚÈ΋˜
Paediatriki 2003;66:97-103
·ÈÙÈÔÏÔÁ›·˜. °›ÓÂÙ·È Ôχ ÛÔ‚·Úfi Úfi‚ÏËÌ· ηٿ ÙË Ê¿ÛË ¯ÔÚ‹ÁËÛ˘ ÙˆÓ ˘ÁÚÒÓ ·Ó·Ï‹ÚˆÛ˘. ÛÙ. ∏ ¤ÎÙˆÛË Ù˘ ηډȷ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ (Ì˘ÔηډÈÔ¿ıÂÈ·) Â›Ó·È Û˘¯Ó‹. OÊ›ÏÂÙ·È ÛÙËÓ ÙÚȯÔÂȉÈ΋ ‰È·Ê˘Á‹, ÛÙË Û˘ÌÊfiÚËÛË ÙÔ˘ ·ÁÁÂÈ·ÎÔ‡ ‰ÈÎÙ‡Ô˘ ÙˆÓ ÈÛÙÒÓ, ÛÙÔ ‰È¿ÌÂÛÔ Ô›‰ËÌ· Î·È ÛÙËÓ ÂÚÈ·ÁÁÂȷ΋ ÊÏÂÁÌÔÓÒ‰Ë ‰È‹ıËÛË, Ì ÌÔÓÔ‡ÚËÓ· ·ÙÙ·Ú· Ô˘ ÂȉÚÔ‡Ó ÛÙÔ Ì˘ÔοډÈÔ. ¶ÈÛÙ‡ÂÙ·È fiÙÈ Ë ‰Ú¿ÛË Ù˘ ÙÔ͛Ӣ ÛÙ· ·ÙÙ·Ú· Î·È Ë ‰Ú¿ÛË ÙÔ˘ TNF ÛÙÔ ‰È·ÊÔÚÈÎfi ‰˘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›· ·ÔÙÂÏÔ‡Ó ‰‡Ô ·Ú¿ÍÂÓ˜ ÂΉËÏÒÛÂȘ ÙÔ˘ TSS. ∆Ô ¯·ÌËÏfi Ca ÔÊ›ÏÂÙ·È ÂÓ Ì¤ÚÂÈ ÛÙËÓ ˘ÔÚˆÙÂ˚Ó·ÈÌ›·, ·ÏÏ¿ Ê·›ÓÂÙ·È fiÙÈ Û˘Ó‰¤ÂÙ·È Î·È Ì ٷ ˘„ËÏ¿ ›‰· ÌÔÚÊ‹˜ ηÏÛÈÙÔÓ›Ó˘, Ë ÔÔ›· ¤¯ÂÈ ÌÂÙÚËı› ÛÙÔ TSS Î·È ¤¯ÂÈ ‰È·ÊÔÚÂÙÈÎfi ÌÔÚÈ·Îfi ‚¿ÚÔ˜ ·fi ÙË Ê˘ÛÈÔÏÔÁÈ΋. 4. ÂΉËÏÒÛÂȘ ·fi ÙÔ ‰¤ÚÌ· Î·È ÙÔ˘˜ ‚ÏÂÓÓÔÁfiÓÔ˘˜ (¶›Ó·Î·˜ 1). ∫ÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ·fiÙÔÌË ¿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 ÛÙÔ ‰È¿¯˘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‡ÙÂÚÔ ÙÔ˘ 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‡ÚËÓˆÓ ÚÔ˜ 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΋˜ ʈÛÊ·Ù¿Û˘ (CPK) ÛÙÔÓ ÔÚfi (Èı·Ófiٷٷ ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ‰Ú¿Û˘ ÙˆÓ IL-1 Î·È TNF Ô˘ ÚÔηÏÔ‡Ó ÚˆÙÂfiÏ˘ÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÚÔÛÙ·ÁÏ·Ó‰›Ó˘ ∂2, Ô˘ Â›Ó·È ÈÛ¯˘Úfi˜ ‰ÈÂÁ¤ÚÙ˘ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ fiÓÔ˘).
99
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·100
¶·È‰È·ÙÚÈ΋ 2003;66:97-103
Paediatriki 2003;66:97-103
¶›Ó·Î·˜ 1. ¢ÂÚÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ ÙÔ˘ TSS ∂Ή‹ÏˆÛË
ÃÚfiÓÔ˜ ÂÌÊ¿ÓÈÛ˘
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°ÂÓÈÎÂ˘Ì¤ÓË ÎËÏȉ҉˘ ÂÚ˘ıÚÔ‰ÂÚÌ›· ∂ί˘ÌÒÛÂȘ (·Û˘Ó‹ı˘) ∂Ú˘ıÚfiÙ˘ ·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ °ÂÓÈÎÂ˘Ì¤ÓÔ Ô›‰ËÌ· ºÏ‡ÎÙ·ÈÓ˜-Ê˘Û·Ï›‰Â˜ (·Û˘Ó‹ı˘) ∫ÓȉˆÙÈÎfi ÎËÏȉԂϷÙȉ҉˜ ÂÍ¿ÓıËÌ· ∞ÔϤÈÛË ‰·ÎهψÓ-·Ï·ÌÒÓ-ÂÏÌ¿ÙˆÓ ∞ÒÏÂÈ· Ì·ÏÏÈÒÓ-ÔÓ‡¯ˆÓ
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ŒÓÙÔÓÔ ÂÚ‡ıËÌ· ÂÈÂÊ˘ÎfiÙˆÓ Î·È ‚ÏÂÓÓÔÁfiÓˆÓ (ÛÙfiÌ·ÙÔ˜, ÁÏÒÛÛ·˜, Ê¿Ú˘ÁÁ·-ÎfiÏÔ˘, Ù˘Ì·ÓÈ΋˜ ÌÂÌ‚Ú¿Ó˘) ªÔÚÔÂȉ‹˜ ÁÏÒÛÛ· ∞ÈÌÔÚÚ·Á›Â˜ ˘fi ÙÔÓ ÂÈÂÊ˘ÎfiÙ· ∂ÍÂÏÎÒÛÂȘ ÛÙfiÌ·ÙÔ˜-ÎfiÏÔ˘-ÔÈÛÔÊ¿ÁÔ˘-·ÛÙˆ˜
Staphylococcus aureus ÌÔÚ› Ó· ·ÔÌÔÓˆı› ·fi ÙËÓ ÂÛÙ›· Ïԛ̈͢ Û ÔÛÔÛÙfi >85% ÙˆÓ ÂÚÈÙÒÛˆÓ. ∆· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ TSST-1 ηٿ ÙËÓ ÔÍ›· Ê¿ÛË ·Ô˘ÛÈ¿˙Ô˘Ó, ÂÓÒ Î·Ù¿ ÙËÓ ·Ó¿ÚÚˆÛË ˘¿Ú¯ÂÈ ˘„ËÏfi˜ Ù›ÙÏÔ˜ ·ÓÙÈۈ̿وÓ. OÈ ·ÈÌÔηÏÏȤÚÁÂȘ ·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·ÓÙÈ Â͈ÙÔÍÈÓÒÓ, ·ÏÏ¿ Ù›ıÂÙ·È ·ÔÎÏÂÈÛÙÈο Ì ÎÏÈÓÈο ÎÚÈÙ‹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΋˜ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ >15 mmHg ηٿ ÙË ÌÂÙ¿‚·ÛË ·fi ÙËÓ Î·Ù·ÎÂÎÏÈ̤ÓË ÛÙËÓ fiÚıÈ· ı¤ÛË, ÔÚıÔÛÙ·ÙÈÎfi Û˘ÁÎÔÈÎfi 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˘ ÓfiÛÔ˘), Ì˘˚ÎÔ‡ (ÛËÌ·ÓÙÈ΋ Ì˘·ÏÁ›· ‹ CPK ÔÚÔ‡ >2Ï¿ÛÈÔ Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ÙÈÌ‹˜), ‚ÏÂÓÓÔÁfiÓˆÓ (˘ÂÚ·ÈÌ›· ÂÈÂÊ˘ÎfiÙˆÓ, ÛÙÔÌ·ÙÔÊ¿Ú˘ÁÁ·, ÎfiÏÔ˘), 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·ÙÔÏÈÛÌÔ‡ ‹ ÙÔ˘ ÂȤ‰Ô˘ Û˘Ó›‰ËÛ˘, ¯ˆÚ›˜ ÂÛÙȷο Ó¢ÚÔÏÔÁÈο ÛËÌ›·, › ·Ô˘Û›·˜ ˘ÚÂÙÔ‡ Î·È ˘fiÙ·Û˘). ÛÙ) ·ÚÓËÙÈο ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ·ÎfiÏÔ˘ıˆÓ ÂÚ-
100
¶ÚÒÈÌË (Û˘¯Ó¿ ·ÚÔ‰È΋) ¶ÚÒÈÌË ¶ÚÒÈÌË ¶ÚÒÈÌË ¶ÚÒÈÌË 7-14 Ë̤Ú˜ 10-21 Ë̤Ú˜ 4-12 ‚‰ÔÌ¿‰Â˜
Á·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛˆÓ, Â¿Ó ÏËÊıÔ‡Ó: i) ηÏÏȤÚÁÂȘ ·›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· ÎËÏÈ‰Ò‰Ë ˘ÚÂÙfi ÙˆÓ ‚Ú·¯ˆ‰ÒÓ ÔÚ¤ˆÓ, ÏÂÙÔÛ›ڈÛË ‹ ÈÏ·Ú¿. ¶Èı·Ó‹ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È fiÙ·Ó ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È 5 ·fi Ù· 6 ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ·, ÂÓÒ Ë ‰È¿ÁÓˆÛË Ù›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‹˜ ηٷϋÍÂÈ ÚÈÓ 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›ËÛË ·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 ÔÈ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÏÔÈÌÒÍÂȘ ı· Ú¤ÂÈ Ó· ·ÚÔ¯ÂÙ‡ÔÓÙ·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˘‰ÂÙÂÚˆı› 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· ¯ÔÚËÁËıÔ‡Ó ÙÔ Û˘ÓÙÔÌfiÙÂÚÔ ‰˘Ó·Ùfi. ¶Ú¤ÂÈ Ó· ¯ÔÚËÁÔ‡ÓÙ·È ˘„ËϤ˜ ‰fiÛÂȘ Ê·Ú̿ΈÓ, ‰ÈfiÙÈ ÔÈ ¯·ÌËϤ˜ 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˘, ‰ÈfiÙÈ Ë ÎÏÈÓ‰·Ì˘Î›ÓË Î·È ÔÈ ¿ÏϘ Ì·ÎÚÔÏ›‰Â˜ ·Ó·ÛÙ¤ÏÏÔ˘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 ¯·ÌËÏfiÙÂÚË ÙÔ˘ 1/64 Ù˘ ÌÈÎÚfiÙÂÚ˘ ·Ó·ÛÙ·ÏÙÈ΋˜ Û˘ÁΤÓÙÚˆÛ˘ (10). Á) ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ Û˘ÛÙËÌ·ÙÈÎÒÓ ÂΉËÏÒÛÂˆÓ ·fi ÙËÓ ÙÔÍ›ÓË ‹ ÙÔ˘˜ ÌÂÙ·‚È‚·ÛÙ¤˜. ™Â
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·101
¶·È‰È·ÙÚÈ΋ 2003;66:97-103
Paediatriki 2003;66:97-103
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 ·fi ÙË ‰Ú¿ÛË Ù˘ TSST-1. ∏ IVIG ÂÚȤ¯ÂÈ ˘„ËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ·Ó·ÛÙ·ÏÙÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÂÓ·ÓÙ›ÔÓ Ù˘ TSST-1 Î·È ¿ÏÏˆÓ ÛÙ·Ê˘ÏÔÎÔÎÎÈÎÒÓ ÂÓÙÂÚÔÙÔÍÈÓÒÓ (11). ŸÌˆ˜, ÛÙ· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· Ô˘ ¤¯ÂÈ ¯ÚËÛÈÌÔÔÈËı›, ¤¯ÂÈ ·Ú·ÙËÚËı› Âȉ›ӈÛË ÙˆÓ ·ÛıÂÓÒÓ ÌÂÙ¿ ·fi ÌÂÚÈΤ˜ ÒÚ˜ Î·È ‰ÂÓ Û˘ÓÈÛٿٷÈ. ∑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‹, ÎÔÏÏÔÂȉ‹) 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¤˜ ÏÔÈÌÒÍÂȘ ·fi ÛÙÚÂÙfiÎÔÎÎÔ Ù˘ ÔÌ¿‰·˜ ∞. ∂ΉËÏÒÓÂÙ·È Û fiϘ ÙȘ ËÏÈ˘, Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ Î·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¿ ıˆڋıËΠˆ˜ Ô ÌÂÁ·Ï‡ÙÂÚÔ˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË strep-TSS. OÈ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ Â›Ó·È ÛÔÚ·‰ÈΤ˜. ¶·ıÔÁ¤ÓÂÈ· £ÂˆÚÂ›Ù·È fiÙÈ Â›Ó·È ›‰È· Ì ÂΛÓË ÙÔ˘ staphTSS. ¶·Ú’ fiÏ· ·˘Ù¿, ˘¿Ú¯Ô˘Ó Ô˘ÛÈÒ‰ÂȘ ‰È·ÊÔÚ¤˜ ÙfiÛÔ ÛÙËÓ ·ıÔÁ¤ÓÂÛË, fiÛÔ Î·È ÛÙȘ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ (¶›Ó·Î·˜ 2). ¶¤ÓÙ ÙÔ˘Ï¿¯ÈÛÙÔÓ ‰È·ÊÔÚÂÙÈΤ˜ ÛÙÚÂÙÔÎÔÎÎÈΤ˜ 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·ÙËÚÂ›Ù·È Û ·ÛıÂÓ›˜ Ì strep-TSS, ‰ÂÓ Â›Ó·È ÂȉÈ΋ ÁÈ· η̛· ·fi ·˘Ù¤˜ ÙȘ ÙÔ͛Ә (13). ∂›Û˘, ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ ÓÔÛËÚfiÙËÙ·˜, fiˆ˜ ÔÈ ·ÓÙÈÊ·ÁÔ΢ÙÙ·ÚÈΤ˜ ÚˆÙ½Ó˜ ª ÂÈÊ·Ó›·˜ Î·È ÙÔ ÏÈÔÙ¯ÓÔ˚Îfi Ô͇ (Ô˘ ¢ԉÒÓÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ÙÔ˘ TNF-a), ÌÔÚ› 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 ÛÙÔ strep-TSS, ηıÒ˜ Î·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë IVIG ÂÚȤ¯ÂÈ ·ÓÙÈÛÒÌ·Ù· Ô˘ ÂÍÔ˘‰ÂÙÂÚÒÓÔ˘Ó ·ÚÎÂÙÔ‡˜ ÛÙÚÂÙÔÎÔÎÎÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÓÔÛËÚfiÙËÙ·˜, ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ¿Ô„Ë ÁÈ· ÙÔ ÚfiÏÔ ÙˆÓ ÛÙÚÂÙÔÎÔÎÎÈÎÒÓ Â͈ÙÔÍÈÓÒÓ ÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙÔ˘ strep-TSS. ™Â ·ÓÙ›ıÂÛË Ì ÙÔ staph-TSS, ÙÔ strep-TSS Û˘Óԉ‡ÂÙ·È Û˘Ó‹ıˆ˜ ·fi ÛÔ‚·Ú‹ ÙÔÈ΋ Ïԛ̈ÍË ·fi ÛÙÚÂÙfiÎÔÎÎÔ ÔÌ¿‰·˜ ∞, Û˘¯Ó¿ Û˘Óԉ¢fiÌÂÓË ·fi ‚·ÎÙËÚÈ·ÈÌ›·. ∫ÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ∏ ‡ÏË ÂÈÛfi‰Ô˘ ÙÔ˘ ÛÙÚÂÙfiÎÔÎÎÔ˘ ÔÌ¿‰·˜ ∞ ·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙË ÛÙÔ 50% ÙˆÓ ÂÚÈÙÒÛÂˆÓ (12). ∞fi ÙËÓ ¿ÏÏË, ηٷÛÙ¿ÛÂȘ fiˆ˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ, ÙÔÎÂÙfi˜, ÏÔÈÌÒÍÂȘ ‰¤ÚÌ·ÙÔ˜ (·ÓÂÌÔ‚ÏÔÁÈ¿) ‹ ÌÈÎÚfi ‰ÂÚÌ·ÙÈÎfi ÙÚ·‡Ì· ÌÔÚÔ‡Ó Ó· ˘¿ÚÍÔ˘Ó ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË strep-TSS. ∂Ï·ÊÚ¿ ÚÔ‰ÚÔÌÈο Û˘ÌÙÒÌ·Ù· ‰È¿ÚÎÂÈ·˜ 13 ËÌÂÚÒÓ ÌÔÚ› Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó ÚÈÓ ÙËÓ ÂΉ‹ÏˆÛË ˘„ËÏÔ‡ ˘ÚÂÙÔ‡. ¶ÔÛÔÛÙfi 80% ÂÚ›Ô˘ ÙˆÓ ÂÚÈÙÒÛˆÓ, ·ÚÔ˘ÛÈ¿˙ÂÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ·fi ÏÔÈÌÒÍÂȘ Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ (΢ÙÙ·Ú›ÙȘ, ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÏÔÈÌÒÍÂȘ, Ì˘ÔÛ›ÙȘ, ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›ÙȘ). ∆Ô shock Î·È Ë ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ‰‡Ô ·Ú·ÁfiÓÙˆÓ (6): ·) Ù˘ ·Â˘ı›·˜ ‰Ú¿Û˘ Ù˘ ÙÔ͛Ӣ Î·È ÙˆÓ ÌÂÙ·‚È‚·ÛÙÒÓ ÛÙ· ·ÙÙ·Ú· Î·È Ù˘ ÈÛÙÈ΋˜ ÈÛ¯·ÈÌ›·˜, Ô˘ ·Ú¯Èο
¶›Ó·Î·˜ 2. ™˘ÁÎÚÈÙÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ÙÔÍÈÎÒÓ shock Û˘Ó‰ÚfïÓ
∆Ô͛Ә ∞ÓÔÛÔÏÔÁ›· ¶Úfi‰ÚÔÌ· Û˘ÌÙÒÌ·Ù· ¢È¿ÚÎÂÈ· Úfi‰ÚÔÌˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ™Ô‚·ÚfiÙËÙ· Úfi‰ÚÔÌˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ∆ÔÈ΋ Ïԛ̈ÍË
£ÂÙÈ΋ ·ÈÌÔηÏÏȤÚÁÂÈ· ¶fiÓÔ˜ ÛÙËÓ ÂÓÙfiÈÛË Ù˘ Ïԛ̈͢ ∂Í¿ÓıËÌ· Shock ¶ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· ¢È·Ù·Ú·¯¤˜ ‹Í˘ £ÓËÙfiÙËÙ·
Strep TSS
Staph TSS
speA, speB, speC ÛÙÚÂÙÔÎÔÎÎÈο ˘ÂÚ·ÓÙÈÁfiÓ· ∂Ï¿ÙÙˆÛË ÎÏÒÓÔ˘ V‚ °Ú›Ë˜-like ∞fi ÒÚ˜ ̤¯ÚÈ Ë̤Ú˜ + +++ (.¯. Ó¢ÌÔÓ›·, Ïԛ̈ÍË ÔÛÙÒÓ, ΢ÙÙ·Ú›ÙȘ, ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›ÙȘ) +++ +++ OÛÙÚ·ÎÈ҉˜ ¢‡ÛÎÔÏÔ Ó· ·ÓÙÈÌÂÙˆÈÛÙ› +++ +++ À„ËÏ‹
TSST-1, ÂÓÙÂÚÔÙÔ͛Ә ∞‡ÍËÛË ÎÏÒÓÔ˘ V‚ ŒÌÂÙÔ˜-‰È¿ÚÚÔÈ· flÚ˜ +++ +
+ ∂Ú˘ıÚÔ‰ÂÚÌ›· ∞ÓÙÈÌÂÙˆ›˙ÂÙ·È + + ÷ÌËÏ‹
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ÔÊ›ÏÂÙ·È ÛÙËÓ ·ÒÏÂÈ· ÙÔ˘ ÙfiÓÔ˘ ÙˆÓ ·ÁÁ›ˆÓ Î·È ‚) ÛÙÔ ÂÎÙÂٷ̤ÓÔ ‰È¿ÌÂÛÔ Ô›‰ËÌ· Ô˘ Û˘ÌȤ˙ÂÈ Î·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‹˜ ηٿ ÙË ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ·Ó·Ï‹ÚˆÛ˘), Ì˘ÔηډÈÔ¿ıÂÈ· ¢∂¶ Î·È ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (ÓÂÊÚÈ΋ Î·È ÚÔÓÂÊÚÈ΋). ∏ ıÓËÙfiÙËÙ· ·Ó¤Ú¯ÂÙ·È Û ÔÛÔÛÙfi 30-70%. ¢È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· ÁÈ· ÙÔ strep-TSS (8) 1. ∞ÔÌfiÓˆÛË ÛÙÚÂÙfiÎÔÎÎÔ˘ ÔÌ¿‰·˜ ∞: ·. ·fi Ê˘ÛÈÔÏÔÁÈο ÛÙ›ڷ ÂÛÙ›· (.¯. ·›Ì·, ÂÁÎÂÊ·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 (ÙÈ̤˜ >2Ï¿ÛÈÔ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ) ii) ¢È·Ù·Ú·¯¤˜ ‹Í˘: ∞ª¶ <100.000/mm3 ‹ ¢∂¶ iii) ◊·Ú: ·‡ÍËÛË SGOT, SGPT ‹ ÔÏÈ΋˜ ¯ÔÏÂÚ˘ıÚ›Ó˘ (ÙÈ̤˜ >2Ï¿ÛÈÔ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ) iv) ARDS v) ∂Í¿ÓıËÌ· ÎËÏȉ҉˜, Ô˘ ÌÔÚ› Ó· ÂÍÂÏȯı› Û ·ÔϤÈÛË vi) ¡¤ÎÚˆÛË Ì·Ï·ÎÒÓ ÌÔÚ›ˆÓ, ÂÚÈÏ·Ì‚¿ÓÔÓÙ·˜ ÓÂÎÚˆÙÈ΋ ÂÚÈÙÔÓ›Ùȉ· ‹ Ì˘ÔÛ›Ùȉ· ‹ Á¿ÁÁÚ·ÈÓ·. ∏ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È Ì ‚‚·ÈfiÙËÙ· fiÙ·Ó ÂÚÈÏ·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 Â›Ó·È ›‰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 ÛÎÂÙÈÎfi 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·ÙÈΤ˜ (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˘
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Ù˘ ÚˆÙ½Ó˘ ª. ™˘ÓÈÛٿٷÈ, ›Û˘, ¯ÔÚ‹ÁËÛË IVIG ÂÓ‰ÔÊÏ‚›ˆ˜, Ë ÔÔ›· ‚ÂÏÙÈÒÓÂÈ ÙËÓ ¤Î‚·ÛË ÙÔ˘ strepTSS (11). ¶ÚÔʇϷÍË ∏ ÂÊ·ÚÌÔÁ‹ ·ÓÙÈÌÈÎÚԂȷ΋˜ ·ÁˆÁ‹˜ ÓˆÚ›˜, Û ¤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 strepTSS. 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 (Suppl 1):S14-S21. 2. Jacobson JA, Kasworm EM, Reiser RF, Bergdoll MS. Low incidence of toxic shock syndrome in children with staphylococcal infection. Am J Med Sci 1987;294:403-407. 3. Lee VT, Chang AH, Chow AW. Detection of staphylococcal enterotoxin B among toxic shock syndrome (TSS)- and non-TSS-associated Staphylo-coccus aureus isolates. J Infect Dis 1992;166: 911-915. 4. Parsonnet J. Nonmenstrual toxic shock syndrome: new insights into diagnosis, pathogenesis, and treatment. Curr Clin Top Infect Dis 1996;16:1-20. 5. Chesney PJ, Davis JP. Toxic shock syndrome. In: Feigin RD, Cherry JD, editors. Textbook of Pediatric Infectious Diseases. 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. A new staphylococcal enterotoxin, enterotoxin F, associated with toxic shock syndrome Staphylococcus aureus isolates. Lancet 1981;1:1017-1021. 8. Spentzas T. Index of suspicion. Case 1. Toxic shock syndrome. Pediatr Rev 1999;20:199-201. 9. Kernodle DS, McGraw PA, Barg NL, Menzies BE, Voladri RK, Harshman S. Growth of Staphylococcus aureus with nafcillin in vitro induces alpha-toxin production and increases the lethal activity of sterile broth filtrates in a murine model. J Infect Dis 1995;172:410-419. 10. Schlievert PM, Kelly JA. Clindamycin-induced suppression of toxic shock syndrome-associated exotoxin production. J Infect Dis 1984;149:471. 11. Kaul R, McGeer A, Norrby-Teglund A, Kotb M, Schwartz B, O’Rourke K et al. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome - a comparative observational study. The Canadian Streptococcal Study Group. 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
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children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group. Pediatrics 2000;105:60. Watanabe-Ohnishi R, Low DE, McGeer A, Stevens DL, Schlievert PM, Newton D et al. Selective depletion of V betabearing T cells in patients with severe invasive group A streptococcal infections and streptococcal toxic shock syndrome. Ontario Streptococcal Study Project. J Infect Dis 1995;171:74-84. Stevens DL, Yan S, Bryant AE. Penicillin-binding protein expression at different growth stages determines penicillin efficacy in vitro and in vivo: an explanation for the inÔculum effect. J Infect Dis 1993;167:1401-1405. Schlievert PM, Shands KN, Dan BB, Schmid GP, Nishimura RD. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis 1981;143:509-516. Vergeront JM, Stolz SJ, Crass BA, Nelson DB, Davis JP,
Begdoll MS. Prevalence of serum antibody to staphylococcal enterotoxin F among Wisconsin residents: implications for toxic shock syndrome. J Infect Dis 1983;148:692-698. 17. Notermans S, van Leeuwen WJ, Dufrenne J, Tips PD. Serum antibodies to enterotoxins produced by Staphylococcus aureus with special reference to enterotoxin F and toxic shock syndrome. J Clin Microbiol 1983;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·
¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›· ™Ô˘‰·ÈfiÙËÙ· ÙˆÓ ÔͤˆÓ ·Ó·Ó¢ÛÙÈÎÒÓ ÏÔÈÌÒÍÂˆÓ ·fi Mycoplasma pneumoniae Î·È Chlamydia pneumoniae Û ·È‰È¿ Ì ÂÎÓ¢ÛÙÈÎfi Û˘ÚÈÁÌfi1 ™ÎÔfi˜ - ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: °È· ÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÚfiÏÔ˘ ÙÔ˘ ª. pneumoniae Î·È ÙÔ˘ C. pneumoniae ÛÙËÓ ·ÓÙȉڷÛÙÈ΋ 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· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÂȤ‰ˆÓ ÂȉÈÎÒÓ ·ÓÙÈۈ̿وÓ, ηıÒ˜ Î·È ÚÈÓÔÊ·Ú˘ÁÁÈÎfi ¤ÎÎÚÈÌ· ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ‰ÂÛÔ͢ÚÈ‚ÔÓÔ˘ÎÏÂ˚ÎÔ‡ ÔͤԘ ÙÔ˘ M. pneumoniae Î·È ÙÔ˘ C. pneumoniae, ηٿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙˆÓ ·ÛıÂÓÒÓ Î·È 4-6 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿. ŸÏ· Ù· ·È‰È¿ ÌÂ Û˘ÚÈÁÌfi ·ÓÙÈÌÂÙˆ›ÛÙËÎ·Ó Ì ηıÔÚÈṲ̂ÓË ·ÁˆÁ‹, Ô˘ ÂÚÈÂÏ¿Ì‚·Ó ÂÈÛÓÂfiÌÂÓ· ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ Î·È ‚ÚÔÁ¯Ô‰È·ÛÙ·ÏÙÈο ÁÈ· 5-7 Ë̤Ú˜. ŸÙ·Ó, ˘fi ÙËÓ ÎÚ›ÛË ÙÔ˘ ÂÊËÌÂÚ‡ÔÓÙÔ˜ È·ÙÚÔ‡, ÚÔÛÙ¤ıËΠ·ÓÙÈ‚ÈÔÙÈÎfi, ÂÈϤ¯ıËÎÂ Ë ÎÏ·ÚÈıÚÔÌ˘Î›ÓË 15 mg/kg ۈ̷ÙÈÎÔ‡ ‚¿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¤ÛË Ì ·˘Ù¿ ¯ˆÚ›˜ Ïԛ̈ÍË ·fi Ù· ·Ú·¿Óˆ ·ıÔÁfiÓ· (p=0,03). ™˘ÌÂÚ¿ÛÌ·Ù·: ∆· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ÛËÌ·ÙÔ‰ÔÙÔ‡Ó Ì›· ηٷʷӋ 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‹ ‚ÂÏÙ›ˆÛË Ù˘ ÔÚ›·˜ Ù˘ ·ÓÙȉڷÛÙÈ΋˜ ÓfiÛÔ˘ ÙˆÓ ·ÂÚ·ÁˆÁÒÓ Û ·È‰È¿ Ì ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ Ïԛ̈͢ ·fi M. pneumoniae ηÈ/‹ C. pneumoniae.
1 Esposito S, Blasi F, Arosio C, Fioravanti L, Fagetti L, Droghetti R et al Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing Eur Respir J 2000;16:1142-1146
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ORIGINAL ARTICLE
∏ ¯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
¶ÂÚ›ÏË„Ë: ∏ ÙÔÈÚ·Ì¿ÙË Â›Ó·È ¤Ó· Ó¤Ô ·ÓÙÈÂÈÏËÙÈÎfi Ê¿ÚÌ·ÎÔ (∞∂º) Ô˘ ¯ÔÚËÁÂ›Ù·È Û ÂÓ‹ÏÈΘ 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˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Î·È Ù˘ ·ÛÊ¿ÏÂÈ·˜ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘, ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋˜ ·ÁˆÁ‹˜, Û ·È‰È¿ Ì ·ÓıÂÎÙÈΤ˜ ÂÈÏË„›Â˜. H ·Ó·‰ÚÔÌÈ΋ ·˘Ù‹ ÌÂϤÙË ·ÊÔÚÔ‡Û 17 ·ÛıÂÓ›˜ (6 ÎÔÚ›ÙÛÈ· Î·È 11 ·ÁfiÚÈ·), ËÏÈΛ·˜ 4,5-19 ÂÙÒÓ (̤ÛË ËÏÈΛ·: 10,4 ¤ÙË), Ì ̷ÎÚfi¯ÚÔÓË Î·È ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÈÏË„›· (̤ÛË ‰È¿ÚÎÂÈ· ÓfiÛÔ˘: 6,9 ¤ÙË). ªÂ ‚¿ÛË ÙËÓ Ù·ÍÈÓfiÌËÛË Ù˘ ¢ÈÂıÓÔ‡˜ ŒÓˆÛ˘ ηٿ Ù˘ ∂ÈÏË„›·˜, 6 ·ÛıÂÓ›˜ ÂÌÊ¿ÓÈ˙·Ó ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· (3 Û˘Ìو̷ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹) Î·È 11 ÂÛÙȷ΋ (8 Û˘Ìو̷ÙÈ΋, 4 ÎÚ˘ÙÔÁÂÓ‹). ∞fi ·˘ÙÔ‡˜, 8 ÂÌÊ¿ÓÈ˙·Ó Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, 3 ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ (2 Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË), 4 Û‡Ó‰ÚÔÌÔ LennoxGastaut (1 ·Ú¯Èο Ì ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜), 1 Ì˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ Î·È 1 ÁÂÓÈÎÂ˘Ì¤ÓÔ˘˜ ÙÔÓÈÎÔÎÏÔÓÈÎÔ‡˜ 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/24 h Î·È ·˘Í‹ıËΠÛÙ·‰È·Î¿, ·Ó¿ÏÔÁ· Ì ÙËÓ ·ÓÙ·fiÎÚÈÛË ÙˆÓ ·ÛıÂÓÒÓ Û 3-10 mg/kg/24 h. ∏ ·Ú·ÎÔÏÔ‡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-epileptic drug (AED) that is used in adults and in children aged ≥2 years, as adjunctive treatment of focal epilepsy that is resistant to drugs. However, it seems that it may also be useful in children with multiple types of epilepsy, such as Lennox-Gastaut syndrome or in children with epilepsies that are resistant to other anti-epileptic drugs. The aim of the present study was the evaluation of effectiveness and safety in the use of the drug, as adjunctive treatment, in children with drug-resistant epilepsy. In this retrospective study included 17 patients (6 girls and 11 boys), aged between 4.5-19 years (median: 10.4 years) with long-term and drugresistant epilepsy (median disease duration: 6.9 years). Based on the classification of International League Against Epilepsy, 6 had generalized epilepsy (3 symptomatic, 3 cryptogenic) and 11 had focal epilepsy (8 symptomatic, 4 cryptogenic). Of these, 8 had complex partial seizures, 3 had partial seizures (2 with secondary generalization), 4 had Lennox-Gastaut syndrome (1 suffered primarily from infantile spasms), 1 suffered from myoclonic absences and 1 from generalized tonic-clonic seizures. All patients received 1-3 AEDs. Topiramate was added to the treatment regimen that the patients were already taking, at a starting dose of 1 mg/kg/24 h and was gradually increased - depending on the patient’s response - to 3.0-10 mg/kg/24 h. In 11/17 patients (64.7%) demonstrated ≥50% decrease in seizure activity and 6/17 patients (35.2%) became seizure free. Effectiveness was observed in various types of seizures and types of epilepsy especially in any type and etiology focal epilepsy. Adverse effects
∆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
104
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·105
¶·È‰È·ÙÚÈ΋ 2003;66:104-112
Paediatriki 2003;66:104-112
ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi ≥50% ÂÌÊ¿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‹ıËΠ۠ÔÈΛÏÔ˘˜ Ù‡Ô˘˜ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Î·È Û˘Ó‰ÚfïÓ, ȉȷ›ÙÂÚ· ÛÙËÓ ÔÔÈ·Û‰‹ÔÙ ÌÔÚÊ‹˜ Î·È ·ÈÙÈÔÏÔÁ›·˜ ÂÛÙȷ΋ ÂÈÏË„›·. ¶·ÚÂÓ¤ÚÁÂȘ ÂÌÊ¿ÓÈÛ·Ó 10/17 ·ÛıÂÓ›˜ (58,8%): 4 ·ÒÏÂÈ· ‚¿ÚÔ˘˜ Î·È ·ÓÔÚÂÍ›·, 4 ÂÈıÂÙÈÎfiÙËÙ· Î·È 2 ˘ÓËÏ›· Î·È ‰˘ÛÎÔϛ˜ Û˘ÁΤÓÙÚˆÛ˘. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÙÔÈÚ·Ì¿ÙË ·Ô‰Â›¯ıËΠ·ÚÎÂÙ¿ ·ÔÙÂÏÂÛÌ·ÙÈ΋ Î·È ·ÛÊ·Ï‹˜ ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋ ıÂڷ›· Û 11/17 ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜, Ì ¤Ó· ÌÂÁ¿ÏÔ Â‡ÚÔ˜ ·ÓıÂÎÙÈÎÒÓ ÂÈÏË„ÈÒÓ, ÙfiÛÔ ÎÚ˘ÙÔÁÂÓÒÓ fiÛÔ Î·È Û˘Ìو̷ÙÈÎÒÓ. ¶·Ú·ÙËÚ‹ıËΠ·ÓÙ·fiÎÚÈÛË Û ÔÛÔÛÙfi ≥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·Ó ˆ˜ › ÙÔ Ï›ÛÙÔÓ ‹È˜ Î·È ·ÚÔ‰ÈΤ˜. ∆¤ÛÛÂÚȘ ·ÛıÂÓ›˜ (23,5%) ‰È¤ÎÔ„·Ó ÙËÓ ·ÁˆÁ‹.
were observed in 10/17 patients (58.8%) and included weight loss and loss of appetite in 4, aggressiveness in 4, somnolence and difficulty in concentration in 2 patients. As a conclusion, topiramate was shown to be quite effective and safe as adjunctive therapy in 11/17 children and adolescents, with a wide range of cryptogenic and symptomatic resistant epilepsies. Response ≥50% was observed in 64.7% of the children in the study. The drug was generally well tolerated and the adverse effects of the drug that were found in 58.8% of the patients, were generally mild and transient. Four patients withdrew from treatment (23.5%).
§¤ÍÂȘ ÎÏÂȉȿ: ÙÔÈÚ·Ì¿ÙË, ·ÓıÂÎÙÈΤ˜ ÛÙ· Ê¿Ú̷η ÂÈÏË„›Â˜, ·È‰È΋ ËÏÈΛ·.
Key words: topiramate, drug resistant epilepsies, childhood.
™˘ÓÙÔÌÔÁڷʛ˜ AEº AED KN™ CBZ OXC PHT VGB LTG CLB VPA TGB PB ETM TPM CORT CLZ ACTH ∂ æ∫∂ MRI IVH GABA
∞ÓÙÈÂÈÏËÙÈÎfi Ê¿ÚÌ·ÎÔ Anti-epileptic drug ∫ÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ· ∫·Ú‚·Ì·˙›ÓË OÍηڂ·˙›ÓË º·ÈÓ˘ÙÔ˝ÓË µÈÁη̷ÙÚ›ÓË §·ÌÔÙÚÈÁ›ÓË ∫ÏÔÌ·˙¿ÌË µ·ÏÚÔ˚Îfi Ô͇ ∆È·Áη̛ÓË º·ÈÓÔ‚·Ú‚ÈÙ¿ÏË ∞ÈıÔÛÔ˘ÍÈÌ›‰Ë ∆ÔÈÚ·Ì¿ÙË ∫ÔÚÙÈÎÔÂȉ‹ ∫ÏÔÓ·˙¿ÌË ™˘ÓıÂÙÈ΋ ·‰ÚÂÓÔÎÔÚÙÈÎÔÙÚfiÔ˜ ÔÚÌfiÓË ∂ÈÏË„›· æ˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍË ª·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘ ∂Ó‰ÔÎÔÈÏȷ΋ ·ÈÌÔÚÚ·Á›· °¿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·Ú̷΢ÙÈ΋˜ ıÂڷ›·˜ Î·È Î·Ù¿ ηÓfiÓ· Ô‰ËÁÂ›Ù·È ÛÙËÓ ÔÏ˘Ê·Ú̷Λ· (1). ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜, Ë ÚfiÁÓˆÛË ·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 (.¯. ÙÔÓÈΤ˜ ‹ ·ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ). ¶·ÚfiÌÔÈ·, Ë ·ÓıÂÎÙÈÎfiÙËÙ· ÛÙËÓ ·ÁˆÁ‹ Â›Ó·È Û˘Ó‹ı˘ ÁÈ· ÔÚÈṲ̂ӷ ÂÈÏËÙÈο Û‡Ó‰ÚÔÌ· (Û‡Ó‰ÚÔÌÔ Lennox-Gastaut, Û‡Ó‰ÚÔÌÔ West) ‹ ÂÍÂÏÈÎÙÈΤ˜ Ó¢ÚÔÏÔÁÈΤ˜ ·ı‹ÛÂȘ (.¯. ÚÔԉ¢ÙÈ΋ Ì˘ÔÎÏÔÓÈ΋ ÂÈÏË„›·), ·ÏÏ¿ Î·È ÁÈ· ÙȘ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ Ì ‹ ¯ˆÚ›˜ ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË (2,3). ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜, Ì ٷ ·ÓˆÙ¤Úˆ ÂÈÏËÙÈο Û‡Ó‰ÚÔÌ· Î·È ÂÈÏË„›Â˜, ÔÈ Ó¢ÚÔ·ÎÙÈÓÔÏÔÁÈΤ˜ ÂÍÂÙ¿ÛÂȘ ÌÔÚ› Ó· ‰Â›ÍÔ˘Ó ‰È¿¯˘Ù˜ ÂÁÎÂÊ·ÏÈΤ˜ ‹ ÂÛÙȷΤ˜ ‚Ï¿‚˜ ÙÔ˘ ∫¡™, ÂÓÒ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡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˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û ÂÓ‹ÏÈΘ Î·È ·È‰È¿ ËÏÈΛ·˜ ≥2 ÂÙÒÓ, ˆ˜ Û˘ÌÏËڈ̷ÙÈ΋ ıÂڷ›· Û ÂÛÙÈ·ÎÔ‡˜ Û·ÛÌÔ‡˜, Ì ‹ ¯ˆÚ›˜ ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË, ηıÒ˜ Î·È Û ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Ú˘ıÌ›˙ÔÓÙ·È Ì ٷ ÎÏ·ÛÈο AEº (4,5). ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ Ê¿ÚÌ·ÎÔ ÌÔÚ› Ó· Â›Ó·È ¯Ú‹ÛÈÌÔ Î·È Û ÔÏÏÔ‡˜ ¿ÏÏÔ˘˜ Ù‡Ô˘˜ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ ‹ ÂÈÏËÙÈÎÒÓ Û˘Ó‰ÚfiÌˆÓ (ÁÂÓÈÎÂ˘Ì¤Ó˜ ÂÈÏË„›Â˜, ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜, Û‡Ó‰ÚÔÌÔ Lennox-Gaustaut) (6-9).
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¶ÔÏ˘Î˘ÛÙÈ΋ ÂÁÎÂÊ·ÏÔÌ·Ï¿Î˘ÓÛË ∞ƒ ËÌÈÛÊ·ÈÚ›Ô˘
¶·È‰È·ÙÚÈ΋ 2003;66:104-112
ŒÓ·ÚÍË 12 ÂÙÒÓ: ÎÚ›ÛÂȘ Ì ·È̈‰›· ¢∂ Á·ÛÙÚÔÎÓËÌ›·˜, ÙÒÛË ÛÙÔ ¤‰·ÊÔ˜, ·ÒÏÂÈ· Û˘Ó›‰ËÛ˘, Ì˘ÔÎÏÔӛ˜, ·Ó‡„ˆÛË ¯ÂÚÈÒÓ, ·Ê·›ÚÂÛË Ì ·fiÙÔÌÔ ‹¯Ô
ŒÓ·ÚÍË 4 ÂÙÒÓ: Ïfi͢ÁÁ·˜, ¿ÓÔÈ·, ÚÔۋψÛË ‚ϤÌÌ·ÙÔ˜ Î·È ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ
ŒÓ·ÚÍË 5 ÂÙÒÓ: ¤ÌÂÙÔÈ, ÔÛÌ‹, Êfi‚Ô˜, ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ
ŒÓ·ÚÍË 9 ÂÙÒÓ: ÙÔÓÈ΋ Û‡Û·ÛË Î·È ·Ó‡„ˆÛË ¿Óˆ ¿ÎÚÔ˘, ·Ê·ÈÚ¤ÛÂȘ, ÙÒÛË ÎÂÊ·Ï‹˜
ŒÓ·ÚÍË 7 ÂÙÒÓ: ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ (˙¿ÏË, ÛÈÂÏfiÚÚÔÈ·, ÙÒÛË ÁˆÓ›·˜ ÛÙfiÌ·ÙÔ˜, ‰˘Û·ÚıÚ›·, Û‡Á¯˘ÛË)
ŒÓ·ÚÍË 4 ÂÙÒÓ: ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ (ÌÂÙ¿ ·fi ÂÚËÙÈ΋ ÂÁÎÂÊ·Ï›Ùȉ·) ∞fi ËÏÈΛ· 7 ÂÙÒÓ: ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, ¿Ù˘Â˜ ·Ê·ÈÚ¤ÛÂȘ, drop attacks
ŒÓ·ÚÍË: ÛÙÔ 1Ô 24ˆÚÔ ˙ˆ‹˜ ™Â ËÏÈΛ· 3 ÂÙÒÓ: status ∞fi ËÏÈΛ· 5 ÂÙÒÓ: Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ
™ÎÏ‹Ú˘ÓÛË ·ÌÌˆÓ›Ô˘ ΤڷÙÔ˜ ∞ƒ ÎÚÔÙ·ÊÈÎÔ‡ ÏÔ‚Ô‡
¶ÔÏ˘ÌÈÎÚÔÁ˘Ú›· ÈÓÈ·ÎÔ‡ ÏÔ‚Ô‡ ¢∂
MRI
14:48
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ - ™˘Ìو̷ÙÈ΋
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ - ™˘Ìو̷ÙÈ΋
∂ Û‡Ó‰ÚÔÌÔ
14-05-03
ŒÓ·ÚÍË 3,5 ÂÙÒÓ: ¢∂ ÂÛÙÈ·Îfi status, Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË ŒÎÙÔÙÂ: Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ
∫ÏÈÓÈ΋ ÂÈÎfiÓ·
∏ÏÈΛ· (º‡ÏÔ) æ∫∂ - ¡Â˘ÚÔÏÔÁÈ΋ ÂÈÎfiÓ·
6 ÂÙÒÓ (∞)
¶›Ó·Î·˜ 1. ∫ÏÈÓÈÎÔÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ÙˆÓ ·ÛıÂÓÒÓ
MARC-APR 03 ™ÂÏ›‰·106
Paediatriki 2003;66:104-112
™Ô‚·Ú‹ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË (·˘ÍË̤ӷ ÔÚÁ·ÓÈο Ôͤ· Ô‡ÚˆÓ)
™Ô‚·Ú‹ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË (Û‡Ó‰ÚÔÌÔ Angelman)
º˘ÛÈÔÏÔÁÈ΋ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍË
ª¤ÙÚÈ· ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË ∏ÌÈÏËÁ›· ∞ƒ
™Ô‚·Ú‹ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË, ·˘ÙÈÛÌfi˜
◊È· ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË - ™‡Ó‰ÚÔÌÔ ÂÏÏÂÈÌÌ·ÙÈ΋˜ ÚÔÛÔ¯‹˜ Î·È ˘ÂÚÎÈÓËÙÈÎfiÙËÙ·˜
™Ô‚·Ú‹ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË ∂ÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË (Û·ÛÙÈ΋ ÙÂÙÚ·ÏËÁ›·) Ì˘ÔÎÏÔӛ˜, ·Ê·ÈÚ¤ÛÂȘ
10 ÂÙÒÓ (∞)
14 ÂÙÒÓ (£)
10 ÂÙÒÓ (£)
9 ÂÙÒÓ (∞)
6 ÂÙÒÓ (∞)
6 ÂÙÒÓ (∞)
5 ÂÙÒÓ (£)
ŒÓ·ÚÍË 4,5 ÌËÓÒÓ: ‚ÚÂÊÈÎÔ› Û·ÛÌÔ› ŒÎÙÔÙÂ: ηÌÙÈÎÔ›, ÙÔÓÈÎÔ› Û·ÛÌÔ›, Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ ÎÚ›ÛÂȘ, - ™˘Ìو̷ÙÈÎfi
ŒÓ·ÚÍË 2 ÂÙÒÓ: ·Ê·ÈÚ¤ÛÂȘ, ·ÙÔÓÈΤ˜ Î·È ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ
ŒÓ·ÚÍË 2 ÂÙÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ Î·È ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ Ì˘ÔÎÏÔӛ˜, ·Ê·ÈÚ¤ÛÂȘ
ŒÓ·ÚÍË 3 ÂÙÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈΤ˜ Î·È ·ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ, ·Ê·ÈÚ¤ÛÂȘ
µÚÂÊÈÎÔ› Û·ÛÌÔ› - Lennox-Gastaut Û‡Ó‰ÚÔÌÔ ·ÙÚÔÊ›·
Lennox-Gastaut Û‡Ó‰ÚÔÌÔ - ∫Ú˘ÙÔÁÂÓ¤˜
Lennox-Gastaut Û‡Ó‰ÚÔÌÔ - ∫Ú˘ÙÔÁÂÓ¤˜
Lennox-Gastaut Û‡Ó‰ÚÔÌÔ - ™˘Ìو̷ÙÈÎfi
¶ÂÚÈÎÔÈÏȷ΋ Ï¢ÎÔÌ·Ï¿Î˘ÓÛË Î·È ÂÏ·ÈÔÁÂÊ˘ÚÔ-·ÚÂÁÎÂÊ·ÏȉÈ΋
º˘ÛÈÔÏÔÁÈ΋
º˘ÛÈÔÏÔÁÈ΋
™˘ÁÁÂÓ‹˜ ÊÏÔÈÈ΋ ‰˘ÛÏ·Û›· ¢∂ ‚ÚÂÁÌ·ÙÈÎÔ‡ ÏÔ‚Ô‡
º˘ÛÈÔÏÔÁÈ΋
º˘ÛÈÔÏÔÁÈ΋
∫‡ÛÙË ‰È·Ê·ÓÔ‡˜ ‰È·ÊÚ¿ÁÌ·ÙÔ˜
14:48
°ÂÓÈÎÂ˘Ì¤ÓË ∂ - ∫Ú˘ÙÔÁÂÓ‹˜
°ÂÓÈÎÂ˘Ì¤ÓË ∂ - ™˘Ìو̷ÙÈ΋
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ™˘Ìو̷ÙÈ΋
14-05-03
ŒÓ·ÚÍË 9 ÌËÓÒÓ-20 ÌËÓÒÓ: ÔÏÏ·ÏÔ› ÂÈÏÂÁ̤ÓÔÈ ˘ÚÂÙÈÎÔ› Û·ÛÌÔ› Î·È status ™Â ËÏÈΛ· 7 ÂÙÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ
ŒÓ·ÚÍË 5 ÌËÓÒÓ-12 ÌËÓÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈΤ˜ ÎÚ›ÛÂȘ Ì ˘ÚÂÙfi Î·È status ∞fi 18 ÌËÓÒÓ: ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ, Ì˘ÔÎÏÔӛ˜ Î·È ·Ê·ÈÚ¤ÛÂȘ
ŒÓ·ÚÍË 4 ÂÙÒÓ: Û‡ÓıÂÙ˜ ÂÛÙȷΤ˜ Î·È ÁÂÓÈÎÂ˘Ì¤Ó˜ ÎÚ›ÛÂȘ
MARC-APR 03 ™ÂÏ›‰·107
¶·È‰È·ÙÚÈ΋ 2003;66:104-112 Paediatriki 2003;66:104-112
107
∂ Û‡Ó‰ÚÔÌÔ
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ - ™˘Ìو̷ÙÈ΋
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ - ™˘Ìو̷ÙÈ΋
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ™˘Ìو̷ÙÈ΋
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ™˘Ìو̷ÙÈ΋
∂ÛÙȷ΋ ∂ - ∫Ú˘ÙÔÁÂÓ‹˜
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ - ∫Ú˘ÙÔÁÂÓ‹˜
∂ÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ™˘Ìو̷ÙÈ΋
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ™˘Ìو̷ÙÈ΋
∂ÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ™˘Ìو̷ÙÈ΋
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ∫Ú˘ÙÔÁÂÓ‹˜
™‡ÓıÂÙË ÂÛÙȷ΋ ∂ Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË - ™˘Ìو̷ÙÈ΋
°ÂÓÈÎÂ˘Ì¤ÓË ∂ - ™˘Ìو̷ÙÈ΋
∏ÏÈΛ· (º‡ÏÔ)
6 ÂÙÒÓ (∞)
9 ÂÙÒÓ (∞)
12 ÂÙÒÓ (∞)
13 ÂÙÒÓ (£)
11 ÂÙÒÓ (∞)
14 ÂÙÒÓ (∞)
14 ÂÙÒÓ (£)
14 ÂÙÒÓ (∞)
19 ÂÙÒÓ (∞)
14 ÂÙÒÓ (£)
10 ÂÙÒÓ (∞)
14 ÂÙÒÓ (£)
¶›Ó·Î·˜ 2. ∞ÔÙÂϤÛÌ·Ù· Ù˘ ·ÁˆÁ‹˜ Ì ∆PM
108 PB, VPA, CLB, CBZ, CLZ, PHT, LTG
CBZ, CLZ, LTG
CBZ, CLB, LTG
PB, PHT, CBZ, CLB
CBZ, VPA
CBZ
CBZ, LTG
VPA, PHT, CBZ
CBZ, TGB
OXC, LTG, VPA
VPA, CBZ
CBZ, CLZ, LTG
CBZ, CLB, TPM
CBZ, PB, TPM
CBZ, VPA, TPM
CBZ, TPM
CBZ, LTG
VPA, PHT
CBZ, TPM
OXC, LTG, VPA, TPM
VP∞, CBZ, TPM
CBZ, TPM
∂ÈıÂÙÈÎfiÙËÙ·, ‰È·Ù·Ú·¯¤˜ Û˘ÁΤÓÙÚˆÛ˘
ÀÓËÏ›·
∞ÒÏÂÈ· ‚¿ÚÔ˘˜ >5 kg
Ÿ¯È
™Ô‚·Ú‹ ˘ÓËÏ›·, ‰È·Ù·Ú·¯¤˜ Û˘ÁΤÓÙÚˆÛ˘
Ÿ¯È
Ÿ¯È
∞ÓÔÚÂÍ›·, ÌÈÎÚ‹ ·ÒÏÂÈ· ‚¿ÚÔ˘˜
∞ÓÔÚÂÍ›·, ÌÈÎÚ‹ ·ÒÏÂÈ· ‚¿ÚÔ˘˜
Ÿ¯È
Ÿ¯È
¶·ÚÂÓ¤ÚÁÂȘ
¢È·ÎÔ‹
5
10
8
5
¢È·ÎÔ‹
¢È·ÎÔ‹
8
5
6,6
6
9
¢fiÛË (mg/kg/d)
-
8 Ì‹Ó˜
9 Ì‹Ó˜
12 Ì‹Ó˜
6 Ì‹Ó˜
-
-
9 Ì‹Ó˜
15 Ì‹Ó˜
10 Ì‹Ó˜
6 Ì‹Ó˜
10 Ì‹Ó˜
¢È¿ÚÎÂÈ· ·Ú·Î/ıËÛ˘
∫·Ì›· ·ÓÙ·fiÎÚÈÛË
<50% Ì›ˆÛË
>75% Ì›ˆÛË
>75% Ì›ˆÛË
>75% Ì›ˆÛË
∫·Ì›· ·ÓÙ·fiÎÚÈÛË
∫·Ì›· ·ÓÙ·fiÎÚÈÛË
100% ·ÓÙ·fiÎÚÈÛË
>75% Ì›ˆÛË
>50% Ì›ˆÛË
100% ·ÓÙ·fiÎÚÈÛË
>75% Ì›ˆÛË
ŒÎ‚·ÛË Û·ÛÌÒÓ
¶·È‰È·ÙÚÈ΋ 2003;66:104-112
CBZ, CLB, LTG
PB, VPA, CBZ, VGB, PHT, CLB
VPA, CBZ, PHT, VGB, TGB
VPA, CBZ, OXC
VPA, CBZ, OXC, PHT, VGB, LTG
VPA, CBZ, TGB, VGB, CLZ, OXC
PB, CBZ, VGB, LTG, TGB
OXC, VPA, LTG, CBZ
PB, VPA, LTG, TGB, OXC, CBZ
CBZ, VGB
CBZ, TPM
∞ÁˆÁ‹ ÙÒÚ·
14:48
CBZ, VGB
CBZ, LTG, TGB
∞ÁˆÁ‹ ÚÔ ∆PM
14-05-03
VPA, CBZ, VGB, LTG
¶ÚÔËÁÔ‡ÌÂÓ· Ê¿Ú̷η
MARC-APR 03 ™ÂÏ›‰·108
Paediatriki 2003;66:104-112
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·109
<50% ·ÓÙ·fiÎÚÈÛË 10 µÚÂÊÈÎÔ› Û·ÛÌÔ› Lennox-Gastaut Û‡Ó‰ÚÔÌÔ - ™˘Ìو̷ÙÈÎfi 5 ÂÙÒÓ (£)
VPA, PB, ACTH, PHT, VGB, LTG, CLZ
VPA, PB, VGB
VPA, PB, VGB, TPM
∞ÓÔÚÂÍ›·, ˘ÓËÏ›·
9 Ì‹Ó˜
100% ·ÓÙ·fiÎÚÈÛË 3 Lennox-Gastaut Û‡Ó‰ÚÔÌÔ - ∫Ú˘ÙÔÁÂÓ¤˜ 6 ÂÙÒÓ (∞)
VPA, CLB, LTG
VPA, LTG
VPA, LTG, TPM
∂ÈıÂÙÈÎfiÙËÙ·
9 Ì‹Ó˜
∫·Ì›· ·ÓÙ·fiÎÚÈÛË ¢È·ÎÔ‹ Lennox-Gastaut Û‡Ó‰ÚÔÌÔ - ∫Ú˘ÙÔÁÂÓ¤˜ 6 ÂÙÒÓ (∞)
VPA, CBZ, LTG, VGB, CLB, CORT
LTG, TGB, CLB
LTG, CLB
∂Í·ÈÚÂÙÈ΋ ÂÈıÂÙÈÎfiÙËÙ·
-
100% ·ÓÙ·fiÎÚÈÛË 5 ∞ÓÔÚÂÍ›·, ÌÈÎÚ‹ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ VPA, TPM VPA, CLB, LTG Lennox-Gastaut Û‡Ó‰ÚÔÌÔ - ™˘Ìو̷ÙÈÎfi 9 ÂÙÒÓ (∞)
VPA, CLB, ETM, LTG, Sandoglobulin
°ÂÓÈÎÂ˘Ì¤ÓË ∂ - ∫Ú˘ÙÔÁÂÓ‹˜ 10 ÂÙÒÓ (£)
PB, VPA
VPA
VPA, TPM
3
15 Ì‹Ó˜
Paediatriki 2003;66:104-112
Ÿ¯È
5 Ì‹Ó˜
100% ·ÓÙ·fiÎÚÈÛË
¶·È‰È·ÙÚÈ΋ 2003;66:104-112
∏ ÙÔÈÚ·Ì¿ÙË Î·Ù·Ù¿ÛÛÂÙ·È ¯ËÌÈο ÛÙÔ˘˜ ÛÔ˘ÏÊ·Ì·ÙÔ-ÌÔÓÔ۷ί·Ú›Ù˜ Î·È ‰Ú· ΢ڛˆ˜ ̤ۈ Ù˘ ·Ó·ÛÙÔÏ‹˜ Ù˘ ÂͿψÛ˘ Ù˘ ÂÈÏËÙÈ΋˜ ÎÚ›Û˘, ·ÏÏ¿ Ù·˘Ùfi¯ÚÔÓ· ÌÔÚ› Ó· ·Ó‚¿˙ÂÈ Î·È ÙÔÓ ÂÈÏËÙÈÎfi Ô˘‰fi. Œ¯ÂÈ ÔÏÏ·Ïfi Ì˯·ÓÈÛÌfi ‰Ú¿Û˘ Î·È Ê·›ÓÂÙ·È fiÙÈ ·›˙ÂÈ Ú˘ıÌÈÛÙÈÎfi ÚfiÏÔ ÛÙÔ˘˜ ÂÓÂÚÁÔÔÈË̤ÓÔ˘˜ ‰È·‡ÏÔ˘˜ Ó·ÙÚ›Ô˘ (·ÔÎÏ›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˘ ‰ÈÂÁÂÚÙÈ΋˜ 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 Ì ̷ÎÚfi¯ÚÔÓË Î·È ·ÓıÂÎÙÈ΋ ÛÙ· Ê¿Ú̷η ÂÈÏË„›·, Ì ̤ÛË ‰È¿ÚÎÂÈ· 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˘ÌÌÂÙ›¯·Ó Û˘ÓÔÏÈο 17 ·È‰È¿, 11 ·ÁfiÚÈ· Î·È 6 ÎÔÚ›ÙÛÈ·. ∏ ËÏÈΛ· ÙÔ˘˜ Î˘Ì·ÈÓfiÙ·Ó Û 4,5-19 ¤ÙË (̤ÛË ËÏÈΛ·: 10,4 ¤ÙË) Î·È ÔÈ ÎÚ›ÛÂȘ Û 5 ·È‰È¿ (30%) ›¯·Ó ¤Ó·ÚÍË ÛÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ Ù˘ ˙ˆ‹˜. H ‰È¿ÁÓˆÛË ‚·Û›ÛÙËΠ۠ÎÏÈÓÈο, ËÏÂÎÙÚÔÂÁÎÂÊ·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‡˜ ŒÓˆÛ˘ ηٿ Ù˘ ∂ÈÏË„›·˜ (ILAE, 1989) (12). ™‡Ìʈӷ Ì ·˘Ù‹, 11/17 ·ÛıÂÓ›˜ (64,7% ÙÔ˘ Û˘ÓfiÏÔ˘) ›¯·Ó Û˘Ìو̷ÙÈ΋ ·ÈÙÈÔÏÔÁ›·, ‰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 ÂÓÙfiÈÛË Ù˘ ÓfiÛÔ˘, ÔÈ 11 ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘ ›¯·Ó ÂÛÙȷ΋ ÂÈÏË„›· (8 Û˘Ìو̷ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹) Î·È ÔÈ ˘fiÏÔÈÔÈ 6 ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· (3 Û˘Ìو̷ÙÈ΋, 3 ÎÚ˘ÙÔÁÂÓ‹). ∞Ó·ÊÔÚÈο, 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 3 ÂÛÙȷΤ˜ 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˙ ÁÂÓÈÎÂ˘Ì¤Ó˜ ÙÔÓÈÎÔÎÏÔÓÈΤ˜ ÎÚ›ÛÂȘ, 1 Ì˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ, 1 ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜ ·Ú¯Èο, Ô˘ ÛÙË Û˘Ó¤¯ÂÈ· ÂÍÂÏ›¯ıËÎ·Ó Û ۇӉÚÔÌÔ Lennox-Gastaut ηÈ, Ù¤ÏÔ˜, 3 ·ÛıÂÓ›˜ ›¯·Ó Û‡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·Ú͢ Î·È ÔÈ Ù‡ÔÈ ÙˆÓ ÎÚ›ÛˆÓ, Ô ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ηÈ
109
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·110
¶·È‰È·ÙÚÈ΋ 2003;66:104-112
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 Î·È Ó¢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 Î·È Weschler (·Ó·ÏfiÁˆ˜ Ù˘ ËÏÈΛ·˜ ÙÔ˘˜) Î·È 6 ÂÌÊ¿ÓÈ˙·Ó ÂÁÎÂÊ·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·ÌÔÙÚÈÁ›ÓË, ÎÏÔÌ·˙¿ÌË, ÂÓÒ Ù· ·È‰È¿ Ì ÁÂÓÈÎÂ˘Ì¤Ó· ÂÈÏËÙÈο Û‡Ó‰ÚÔÌ· ›¯·Ó ‰ÔÎÈÌ¿ÛÂÈ ‚·ÏÚÔ˚Îfi, Ï·ÌÔÙÚÈÁ›ÓË Î·È ÎÏÔÌ·˙¿ÌË Û ÌÔÓÔıÂڷ›· ‹ Î·È Û˘Ó‰˘·ÛÌÔ‡˜. ∂›Û˘, ÌÂÚÈο ·È‰È¿ ›¯·Ó ·ÓÙÈÌÂÙˆÈÛÙ› Î·È Ì ¿ÏÏ· ·ÓÙÈÂÈÏËÙÈο 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›ÛÂˆÓ <50%, η̛· ·ÓÙ·fiÎÚÈÛË, ·‡ÍËÛË ÙˆÓ ÎÚ›ÛˆÓ-Âȉ›ӈÛË) 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›ÌËÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÎÚ›ÛÂˆÓ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ËÌÂÚÔÏfiÁÈ· ηٷÁÚ·Ê‹˜ (ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô Î·È ·fi ÙÔ˘˜ ÁÔÓ›˜, ÛÙÔ Û›ÙÈ) Î·È Ù·ÎÙÈ΋ ÌËÓÈ·›· ÂÓ‰ÔÓÔÛÔÎÔÌÂȷ΋ ÎÏÈÓÈ΋ (Î·È ÂÈÏÂÎÙÈο 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¿ÏÔÁ· 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· ÙˆÓ 8 ÂÙÒÓ Î·È 5-8 mg/kg/Ë̤ڷ ÁÈ· Ù· ·È‰È¿ ÌÂÁ·Ï‡ÙÂÚ˘ ËÏÈΛ·˜. ™ÙÔÓ ÏËı˘ÛÌfi Ù˘ ÌÂϤÙ˘ ‰ÂÓ ¤ÁÈÓ ̤ÙÚËÛË ÙˆÓ ÂȤ‰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 ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi ≥50% (Ô˘ ıˆÚÂ›Ù·È ÎÚÈÙ‹ÚÈÔ ÈηÓÔÔÈËÙÈ΋˜ Ú‡ıÌÈÛ˘ ÁÈ· ÙȘ ·ÓıÂÎÙÈΤ˜ ÂÈÏË„›Â˜), ÂÓÒ 6 ·fi ·˘ÙÔ‡˜ ··ÏÏ¿¯ÙËÎ·Ó Ï‹Úˆ˜ (35,2%). ∞Ó·Ï˘ÙÈÎfiÙÂÚ·, ÛÙÔ˘˜ 6 ·ÛıÂÓ›˜ Ô˘ ÔÈ ÂÈÏËÙÈΤ˜ ÎÚ›ÛÂȘ ÂϤÁ¯ıËÎ·Ó Ï‹Úˆ˜, ÔÈ 2 ›¯·Ó Û‡Ó‰ÚÔÌÔ Lennox-Gastaut (1 Û˘Ìو̷ÙÈÎfi, 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-
110
Paediatriki 2003;66:104-112
Ó›˜, Ô˘ fiÏÔÈ Â›¯·Ó Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË„›· Î·È Ì›ˆÛË Û ÔÛÔÛÙfi >50% ·Ú·ÙËÚ‹ıËΠ۠1 ·ÛıÂÓ‹ ÌÂ Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË„›·, ›Û˘. ¶ÂÚÈÔÚÈṲ̂ÓË ·¿ÓÙËÛË ÛÙËÓ ·ÁˆÁ‹ Ì ÂÏ¿ÙÙˆÛË ÙˆÓ ÎÚ›ÛÂˆÓ <50% ÂÌÊ¿ÓÈÛ·Ó 2 ·ÛıÂÓ›˜, ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ 1 ›¯Â ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜, Ô˘ ›¯·Ó ÌÂÙÂÍÂÏȯı› Û ۇӉÚÔÌÔ Lennox-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 ·ÛıÂÓ›˜ Ì ÔÔÈ·Û‰‹ÔÙ ÌÔÚÊ‹˜ ‹ ·ÈÙÈÔÏÔÁ›·˜ ÂÛÙȷ΋ ÂÈÏË„›·, ÛÙÔÓ 1 ·fi ÙÔ˘˜ 2 ·ÛıÂÓ›˜ Ì ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· Î·È ÛÙÔ˘˜ 2 ·fi ÙÔ˘˜ 3 ·ÛıÂÓ›˜ Ì ۇӉÚÔÌÔ Lennox-Gastaut. ∫·Ì›· ·ÏÏ·Á‹ ÛÙË Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ ‰ÂÓ ·ÚÔ˘Û›·Û·Ó 3 ·ÛıÂÓ›˜: 1 Ì ÎÚ˘ÙÔÁÂÓ¤˜ Û‡Ó‰ÚÔÌÔ Lennox-Gastaut, 1 ÌÂ Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË„›· Ì ‰Â˘ÙÂÚÔ·ı‹ ÁÂӛ΢ÛË Î·È 1 ÌÂ Û˘Ìو̷ÙÈ΋ ÁÂÓÈÎÂ˘Ì¤ÓË ÂÈÏË„›· ÌÂ Ì˘ÔÎÏÔÓÈΤ˜ ·Ê·ÈÚ¤ÛÂȘ. ∆¤ÏÔ˜, Âȉ›ӈÛË ÙˆÓ ÎÚ›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 ÚÔÛı‹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˘ η٤ÛÙË ‰˘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¤ÚÁÂȘ. ™ÙËÓ ÏÂÈÔ„ËÊ›· ÙÔ˘˜ ÔÈ ·ÚÂÓ¤ÚÁÂȘ ‹Ù·Ó ‹È˜ Î·È ·ÚÔ‰ÈΤ˜. ∏ ÈÔ Û˘Ó‹ı˘ ‹Ù·Ó Ë ·ÓÔÚÂÍ›· (4 ·ÛıÂÓ›˜), Ë ÔÔ›· ‹Ù·Ó ·ÚÔ‰È΋, ÛÙËÓ ·Ú¯È΋ Ê¿ÛË ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È ÛÙÔ˘˜ ÌÈÎÚfiÙÂÚ˘ ËÏÈΛ·˜ ·ÛıÂÓ›˜, ÌÂ Û˘ÓÔ‰fi ÌÈÎÚ‹ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ (<0,5 kg). ™ËÌ·ÓÙÈ΋ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ (>5 kg) ·Ú·ÙËÚ‹ıËΠÌfiÓÔ Û 1 Ó·Úfi ÂÓ‹ÏÈη 19 ÂÙÒÓ. ∏ ·ÒÏÂÈ· ‚¿ÚÔ˘˜ ·Ú·ÙËÚ‹ıËΠÛÙÔ ÚÒÙÔ 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‡ıÌÈÛË ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛˆÓ, ·Ú·ÙËÚ‹ıËÎ·Ó Û 3 ·ÛıÂÓ›˜. ¢‡Ô ·ÛıÂÓ›˜ ÂÌÊ¿ÓÈÛ·Ó ÂÍ·ÈÚÂÙÈ΋ ÂÈıÂÙÈÎfiÙËÙ· (1 Ì ۇӉÚÔÌÔ Lennox-Gastaut Î·È 1 Ì ÁÂÓÈÎÂ˘Ì¤ÓË Û˘Ìو̷ÙÈ΋ ÂÈÏË„›·, ÏfiÁˆ Û˘Ó‰ÚfiÌÔ˘ Angelman) Î·È Ô ÙÚ›ÙÔ˜ ·ÚÔ˘Û›·Û ¤ÓÙÔÓË ˘ÓËÏ›· Î·È ‰È·Ù·Ú·¯‹ Ù˘ Û˘ÁΤÓÙÚˆÛ˘ (·ÛıÂÓ‹˜ ÌÂ Û˘Ìو̷ÙÈ΋ ÂÛÙȷ΋ ÂÈÏË„›·).
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·111
¶·È‰È·ÙÚÈ΋ 2003;66:104-112
™˘˙‹ÙËÛË ∏ ıÂڷ¢ÙÈ΋ ·ÁˆÁ‹ ÛÙËÓ ÂÈÏË„›· ¤¯ÂÈ Û·Ó Î‡ÚÈÔ ÛÙfi¯Ô ÙËÓ ··ÏÏ·Á‹ ÙˆÓ ·ÛıÂÓÒÓ ·fi ÙȘ ÎÚ›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˘ ۯ‰fiÓ fiÏÔÈ ˘Ô‚¿ÏÏÔÓÙ·Ó Û ÔÏ˘ıÂڷ›· Î·È Û 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.) ‰ÂÓ Â›Ó·È Û˘Ó‹ıˆ˜ ‰˘Ó·Ù‹ Ë Ï‹Ú˘ ··ÏÏ·Á‹ ·fi ÙȘ ÎÚ›ÛÂȘ. ŒÙÛÈ, Ô ıÂڷ¢ÙÈÎfi˜ ÛÙfi¯Ô˜ ÂÚÈÔÚ›˙ÂÙ·È ÛÙË 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 Û ÔÛÔÛÙfi ≥50% ıˆÚÂ›Ù·È ÈηÓÔÔÈËÙÈ΋ Ú‡ıÌÈÛË). ∞fi ÙË ÌÂϤÙË Ê¿ÓËΠfiÙÈ Ë ÙÔÈÚ·Ì¿ÙË ˘‹ÚÍ ·ÔÙÂÏÂÛÌ·ÙÈ΋ Û·Ó Û˘ÌÏËڈ̷ÙÈ΋ ·ÁˆÁ‹ Û ·ÚÎÂÙ¿ ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ·ÛıÂÓÒÓ (64,7% ÙˆÓ ·ÛıÂÓÒÓ, ›¯Â Ì›ˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÂÈÏËÙÈÎÒÓ ÎÚ›ÛÂˆÓ Û ÔÛÔÛÙfi ≥50%). ∂›Û˘, ÛËÌ·ÓÙÈÎfi ‹Ù·Ó Î·È ÙÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ··ÏÏ¿¯ıËÎ·Ó Ï‹Úˆ˜ ·fi ÙȘ ÎÚ›ÛÂȘ (6 ·ÛıÂÓ›˜ ‹ ÔÛÔÛÙfi 35,2% ÙÔ˘ Û˘ÓfiÏÔ˘). ¶·ÚfiÌÔÈ· ·ÔÙÂϤÛÌ·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 Û ÔÛÔÛÙfi ≥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 ÌÂϤÙË ÙÔ˘˜ Ì 34 ·ÛıÂÓ›˜ Ì ·ÓıÂÎÙÈ΋ ÂÈÏË„›· ÔÈÎ›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 ÌÂϤÙ˜ ÙˆÓ Elterman Î·È Û˘Ó, Ô˘ ·ÊÔÚÔ‡Û·Ó ·ÔÎÏÂÈÛÙÈο Û ÂÛÙȷΤ˜ ÂÈÏË„›Â˜, ‰È·ÈÛÙÒıËΠ̛ˆÛË 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 ÙÔÈÚ·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 ÙȘ ÎÚ›ÛÂȘ (>50%) ÛÙÔ 73% ·˘ÙÒÓ, ·ÓÂÍ·Úًو˜ Ù˘ ˘ÔΛÌÂÓ˘, Û ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi, Û˘Ìو̷ÙÈ-
Paediatriki 2003;66:104-112
΋˜ 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) Î·È Ì ‚ÚÂÊÈÎÔ‡˜ Û·ÛÌÔ‡˜ (7). ™Â ÚfiÛÊ·Ù˜, Ì¿ÏÈÛÙ·, ÌÂϤÙ˜ ÚÔÙ›ÓÂÙ·È Ë ¯Ú‹ÛË Ù˘ ÙÔÈÚ·Ì¿Ù˘ ˆ˜ Ê·ÚÌ¿ÎÔ˘ ÚÒÙ˘ ÂÈÏÔÁ‹˜ Î·È ˆ˜ ÌÔÓÔıÂڷ›·˜ Û ڈÙԉȷÁÓˆṲ̂Ó˜ ÂÈÏË„›Â˜, ÈÛfiÙÈÌ˘ ÙÔ˘Ï¿¯ÈÛÙÔÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Ì ÙÔ ‚·ÏÚÔ˚Îfi Ó¿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· ÌÂϤÙË, ·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›ÛÙËÎÂ Î·È Â›¯Â ÌÂÙÂÍÂÏȯı› ÛÙË Û˘Ó¤¯ÂÈ· Û ۇӉÚÔÌÔ Lennox-Gastaut, Ë ·¿ÓÙËÛË ‹Ù·Ó ÌÈÎÚ‹ (Ì›ˆÛË ÙˆÓ 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 ÂÈÏË„›·˜ 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˜ ηٷÛÙÔÏ‹ Î·È ÚÔ‚Ï‹Ì·Ù· Û˘ÁΤÓÙÚˆÛ˘). ∏ ·ÓÔÚÂÍ›· ·ÊÔÚÔ‡Û ΢ڛˆ˜ Û ·ÛıÂÓ›˜ ÌÈÎÚ‹˜ ËÏÈΛ·˜, ‹Ù·Ó ·ÚÔ‰È΋ Î·È ‰ÂÓ Ô‰‹ÁËÛ Û ÛËÌ·ÓÙÈ΋ ·ÒÏÂÈ· ‚¿ÚÔ˘˜, ÂÓÒ ÂÌÊ·Ó›ÛÙËΠÌfiÓÔ 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 ·ÛıÂÓÒÓ Ô˘ ¤·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 ·ӿÎÙËÛË ÙÔ˘ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ‚¿ÚÔ˘˜, ¯ˆÚ›˜ Ó· ÂËÚ¿˙ÂÙ·È Ì·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˘ ÂÈı˘ÌÔ‡Ó ÛÙËÓ ÂÚ›Ô‰Ô ·˘Ù‹ Ù˘ ˙ˆ‹˜ ÙÔ˘˜ Ó· ¯¿ÛÔ˘Ó ‚¿ÚÔ˜, fiˆ˜ ·ÎÚÈ‚Ò˜ Û˘Ó¤‚Ë Î·È ÛÙÔÓ Ó·Úfi ÂÓ‹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˘
111
MARC-APR 03
14-05-03
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‰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˘˜ ‰ÈÂÎfiË ÙÔ Ê¿ÚÌ·ÎÔ, ·ÊÔ‡ ·Ô‰Â›¯ıËΠfiÙÈ ‹Ù·Ó Î·È ·Ó·ÔÙÂÏÂÛÌ·ÙÈÎfi ÛÙË Ú‡ıÌÈÛË ÙˆÓ ÎÚ›ÛˆÓ. ™Â ¿ÏϘ ‰ÈϤ˜-Ù˘ÊϤ˜, ÂÏÂÁ¯fiÌÂÓ˜ Ì placebo ÌÂϤÙ˜, Û ·ÛıÂÓ›˜ Ô˘ ıÂڷ‡ÔÓÙ·Ó Ì ÙÔÈÚ·Ì¿ÙË, ÔÈ ·ÚÂÓ¤ÚÁÂȘ ·fi ÙÔ ∫¡™, fiˆ˜ Ë Û˘Ó·ÈÛıËÌ·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). °ÂÓÈο, ¿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·ÚÌ¿ÎˆÓ (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›Ù Ì ÙË Û˘Ó¤¯ÈÛË Ù˘ ıÂڷ›·˜, ›Ù Ì ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ¯ÔÚËÁÔ‡ÌÂÓ˘ ‰fiÛ˘. ∂ÈÚfiÛıÂÙ·, ÎÚ›ÛÈÌË ÛÙËÓ Î·Ù‡ı˘ÓÛË ·˘Ù‹ Â›Ó·È Ë ·ÚÁ‹ ÙÈÙÏÔÔ›ËÛË ÙˆÓ ‰fiÛÂˆÓ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ (·‡ÍËÛË 1 mg/kg/24 h ·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· Â›Ó·È ·ÛʷϤ˜ Ê¿ÚÌ·ÎÔ, ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ¤ÏÏÂÈ„Ë ÛËÌ·ÓÙÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÔ‚·ÚÒÓ ‹ ·ÂÈÏËÙÈÎÒÓ ÁÈ· ÙË ˙ˆ‹ ·ÚÂÓÂÚÁÂÈÒÓ (11). ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ÙÔÈÚ·Ì¿ÙË Ê¿ÓËΠӷ ‚ÂÏÙÈÒÓÂÈ ÙÔÓ ¤ÏÂÁ¯Ô ÙˆÓ ÎÚ›ÛÂˆÓ Û ‰È¿ÊÔÚ· ÂÈÏËÙÈο Û‡Ó‰ÚÔÌ· ·È‰ÈÒÓ Î·È ÂÊ‹‚ˆÓ (·ÓıÂÎÙÈο Û ¿ÏÏ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η), ¯ÔÚËÁÔ˘Ì¤ÓË Û·Ó Û˘ÌÏËڈ̷ÙÈ΋ ·ÁˆÁ‹ Ì·˙› Ì ¿ÏÏ· ÎÏ·ÛÈο Î·È ÓÂfiÙÂÚ· ·ÓÙÈÂÈÏËÙÈο Ê¿Ú̷η. ¶·Ú·ÙËÚ‹ıËΠ·ÓÙ·fiÎÚÈÛË Û ÔÛÔÛÙfi ≥50%, ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ Ì¤ÚÔ˜ 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΋ ıˆÚÂ›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¿ÛÙËÎ·Ó ÛÙÔ 58,8% ‹Ù·Ó ˆ˜ › ÙÔ Ï›ÛÙÔÓ ‹È˜ Î·È ·ÚÔ‰ÈΤ˜, ÂÓÒ ÌfiÓÔ 4 ·ÛıÂÓ›˜ (23,5%) ‰È¤ÎÔ„·Ó ÙËÓ ·ÁˆÁ‹. £· Ú¤ÂÈ, fï˜, Ó· ÙÔÓÈÛÙ› fiÙÈ ÔÈ ·ÒÙÂÚ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Â›Ó·È ·ÎfiÌË ¿ÁÓˆÛÙ˜.
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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: a review. Eur J Pediatr Neurol 1997;1:139-147. 4. Elterman RD, Glauser TA, Wyllie E, Reife R, Wu SC, Pledger G. A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. ¡eurology 1999;52:1338-1344. 5. Uldall P, Buchholt JM. Clinical experiences with topiramate in children with intractable epilepsy. Eur J Pediatr Neurol 1999;3:105-111. 6. Wheless JW. Use of topiramate in childhood generalized seizure disorders. J Child Neurol 2000;15 (1 suppl):S7-13. 7. Glauser TA, Clark PO, Strawsburg R. A pilot study of topiramate in the treatment of infantile spasms. Epilepsia 1998;39:1324-1328. 8. Glauser TA, Levisohn PM, Ritter F, Sachdeo RC. Topiramate in Lennox-Gastaut syndome: open-label treatment of patients completing a randomized controlled trial. Topiramate YL Study Group. Epilepsia 2000;41 (1 Suppl):S86-90. 9. Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G. A double-blind, randomized trial of topiramate in LennoxGastaut syndrome. Topiramate YL Study Group. Neurology 1999;52:1882-1887. 10. Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 2000;41 (1 Suppl):S3-9. 11. Bourgeois BF. Pharmacokinetics and pharmacodynamics of topiramate. J Child Neurol 2000;15 (1 suppl):S27-30. 12. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification 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 - ÂÌÂÈÚ›· ÂÓfi˜ ¤ÙÔ˘˜. 16Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ∂ÏÏ‹ÓˆÓ ¡Â˘ÚÔÏfiÁˆÓ. £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 Pediatr Neurol 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 in children. J Child Neurol 2000;15 (1 Suppl):S22-26. 17. Shorvon SD. Safety of topiramate: adverse events and relationships 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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Paediatriki 2003;66:113-117
ORIGINAL ARTICLE
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
¶ÂÚ›ÏË„Ë: ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÂÚÁ·Û›·˜ ‹Ù·Ó: ·) Ë Ì¤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ·ÎÂÙ˘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˜ ›Û˘ Î·È Ù˘ ÓÙÔ·Ì›Ó˘ (¡ÙÔ), ‚) Ë ÌÂϤÙË ÙˆÓ in 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 (1,8 mM)+∞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 x mg protein), ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ Ù˘ ∆˘Ú (0,83±0,30 mg/dl) Î·È Ù˘ ¡ÙÔ (56±18 Ìmol/l) ‹Ù·Ó ÛËÌ·ÓÙÈο ÌÂȈ̤Ó˜ (60%, p<0,001) ÛÙËÓ ÔÌ¿‰· µ Û˘ÁÎÚÈÓfiÌÂÓ˜ Ì ÙËÓ ÔÌ¿‰· ∞ (3,01±0,18 ¢OD/min x mg protein, 2,09±0,7 mg/dl, 137±29 Ìmol/l) Î·È Ì ÙÔ˘˜ 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·È Û˘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) to evaluate acetylcholinesterase (AChE) activity in erythrocyte membranes from phenylketonuric (PKU) patients and controls, b) to correlate AChE activity with plasma levels of phenylalanine (Phe), tyrosine (Tyr), alanine (Ala) and dopamine (DA), and c) to determine the in vitro effects of Phe, Ala and Phe plus Ala on AChE activities. AChE activity was determined spectrophotometrically in erythrocyte membranes from 12 PKU children adhering to their diet (group A), from 11 PKU children on a “loose diet” (group B) and from 23 controls. Amino acids were evaluated with an analyser and DA by HPLC. Ala (1.8 mM) and/or Phe (1.8 mM) were added to the enzyme incubation medium from the controls, and Ala alone was added to that from group B. AChE activity (1.19±0.05 ¢OD/min x mg protein), Tyr (0.83±0.30 mg/dl) and DA (56±18 Ìmol/l) were lower by about 60% in group B than in group A (3.01±0.18 ¢OD/min x mg protein, 2.09±0.70 mg/dl, 137±29 Ìmol/l, respectively, p<0.001) and in the control group (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 AChE activity and positively with Tyr and DA. In the control group, Ala reversed the inhibition of AChE by Phe, whereas no effect was observed on the enzyme activity in the PKU patients. In conclusion, a) the determination of AChE in erythrocyte membranes from PKU patients may be a peripheral marker for
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
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Paediatriki 2003;66:113-117
›‰Ú·ÛË Ù˘ º·È ÛÙË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞Ã ÙˆÓ Ì·ÚÙ‡ÚˆÓ. ∞ÓÙ›ıÂÙ·, Ë ∞Ï· ‰ÂÓ Â›¯Â ηӤӷ ·ÔÙ¤ÏÂÛÌ· ÛÙËÓ ∞Ã ÙˆÓ PKU ·ÛıÂÓÒÓ. ™˘ÌÂÚ·ÛÌ·ÙÈο, ·) Ë Ì¤ÙÚËÛË ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ·ÛıÂÓÒÓ Ì PKU ı· ÌÔÚÔ‡Û ӷ ıˆÚËı› ˆ˜ Ô˘ÛÈ҉˘ ‰Â›ÎÙ˘ Ù˘ ÙÔÍÈÎfiÙËÙ·˜ Ù˘ º·È ÛÙÔ ∫¡™, ‚) Ù· ˘„ËÏ¿ ›‰· º·È ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤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˘.
the neurotoxic brain effects of Phe, b) the low levels of DA and its precursor Tyr result from high Phe levels which inhibit AChE in PKU patients, probably causing higher acetylcholine concentrations.
§¤ÍÂȘ ÎÏÂȉȿ: Ê·ÈÓ˘Ï·Ï·Ó›ÓË, ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿ÛË, ÓÙÔ·Ì›ÓË, ·Ï·Ó›ÓË.
Key words: phenylalanine, acetylcholinesterase, dopamine, alanine.
∂ÈÛ·ÁˆÁ‹ ∏ Ê·ÈÓ˘ÏÎÂÙÔÓÔ˘Ú›· (PKU) Â›Ó·È ¤Ó· ÌÂÙ·‚ÔÏÈÎfi ÓfiÛËÌ· Ô˘ ÎÏËÚÔÓÔÌÂ›Ù·È Ì ˘ÔÏÂÈfiÌÂÓÔ ÛˆÌ·ÙÈÎfi ÁfiÓÔ ÌÂ Û˘¯ÓfiÙËÙ· 1:15000 ÁÂÓÓ‹ÛÂȘ. ∏ ‰È·Ù·Ú·¯‹ ·˘Ù‹ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·ÌÈÓÔͤԘ Ê·ÈÓ˘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˘ ·ÌÈÓÔͤԘ 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 (7-20 mg/dl ‹ 0,4-1,2 mª) Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Â›Ó·È È‰È·›ÙÂÚ· ‚Ï·ÙÈο ηٿ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ˙ˆ‹˜. OÈ ‚Ï¿‚˜ ·˘Ù¤˜ ÚÔÏ·Ì‚¿ÓÔÓÙ·È Ì ÙË ÛˆÛÙ‹ ‰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›· Â›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· ÙË ÌÂȈ̤ÓË ·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·È Û ¿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·ÛÙÈÎfiÙËÙ˜ Ù˘ ·ÎÂÙ˘Ï¯ÔÏÈÓÂÛÙÂÚ¿Û˘ (∞Ã) Û ÔÌÔÁÂÓÔÔ›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·Ó Âˆ·ÛıÔ‡Ó ÛÂ Û˘ÁÎÂÓÙÚÒÛÂȘ º·È 7-20 mg/dl ‹ 0,4-1,2 mª, Û‡ÓËı˜ ‡ÚËÌ· ÛÙÔ ·›Ì· PKU ·ÛıÂÓÒÓ 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› ‹ ÚÔÛٷهÂÈ ÙËÓ ∞à ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡ ‹ ηı·ÚÔ‡ ÂÓ˙‡ÌÔ˘ ·fi ÙËÓ ·Ó·ÛÙ·ÏÙÈ΋ ‰Ú¿ÛË Ù˘ º·È. ∞ÎfiÌË, ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ë ∞à ¤ÌÌÂÛ· ÂËÚ¿˙ÂÙ·È ·fi ÙË ¡ÙÔ (11), Ë ÔÔ›· ¤¯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 ÂӉȷʤÚÔÓ Ó· ·Ó¢ÚÂıÔ‡Ó ÂÚÈÊÂÚÈÎÔ› ‰Â›ÎÙ˜, ÔÈ ÔÔ›ÔÈ ı· Â›Ó·È ·ÓÙÈÚÔÛˆÂ˘ÙÈÎÔ› ÙˆÓ ÂȉڿÛÂˆÓ Ù˘ º·È ÛÙÔ ¤Ó˙˘ÌÔ ÙÔ˘ ∫¡™. ™ÙËÓ ·ÚÔ‡Û· ÂÚÁ·Û›· ÌÂÙÚ‹ıËÎÂ Ë ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à Û ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ Î·È Ì·ÚÙ‡ÚˆÓ ·ÓÙ›ÛÙÔȯ˘ ËÏÈΛ·˜, ¤ÁÈÓÂ Û˘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˘ÁÎÂÓÙÚÒÛÂˆÓ º·È, ∞Ï·, ∞Ï·+º·È ÛÙËÓ ∞à ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ PKU ·ÛıÂÓÒÓ, ·ÏÏ¿ Î·È Ì·ÚÙ‡ÚˆÓ.
114
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) ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì ̤ÛË ËÏÈΛ· Ù· 6,8±1,2 ¤ÙË, Ì ۯ‰fiÓ Ê˘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·È 28,45±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 ·ÛıÂÓÒÓ, Ï‹ÊıËΠ·›Ì· 5,0 ml Û ˷ÚÈÓÈṲ̂ÓË Û‡ÚÈÁÁ·, 3 ÒÚ˜ ÌÂÙ¿ ÙËÓ Â›Û΄‹ ÙÔ˘˜, ÒÛÙ ӷ ›¯·Ó ÂÁÎÏÈÌ·ÙÈÛÙ› ÛÙÔ ÂÚÈ‚¿ÏÏÔÓ.
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·115
¶·È‰È·ÙÚÈ΋ 2003;66:113-117
Paediatriki 2003;66:113-117
∂ÓÙfi˜ 2 ˆÚÒÓ ·fi ÙËÓ ·ÈÌÔÏË„›·, ÙÔ ·›Ì· Ê˘ÁÔÎÂÓÙÚ‹ıËΠ(2000 g ÁÈ· 30 min ÛÙÔ˘˜ 4ÔC). ∆o ›˙ËÌ· χıËΠ3-4 ÊÔÚ¤˜ Ì ڢıÌÈÛÙÈÎfi ‰È¿Ï˘Ì· (250 mª tris (hydroxymethyl) aminomethane - HCl (tris HCl), pH 7,4, 140 mM NaCl, 1 mM MgCl2, 10 mM ÁÏ˘Îfi˙Ë) ÌÂÙ¿ ·fi 3 Ê˘ÁÔÎÂÓÙÚ‹ÛÂȘ. ™ÙÔ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎfi ›˙ËÌ· ÚÔÛÙ¤ıËΠ1 ml 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΢ÙÙ·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 (527A Sigma Chemical Co, St. Louis, USA) Î·È Ë ÙÈÌ‹ Ù˘ ·Ê·ÈÚ¤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 vitro ÚÔÂÒ·ÛË ÁÈ· 1 ÒÚ· Ì º·È 30 mg/dl (=1,8 mª) ‹ 1,8 mª ∞Ï· ‹ º·È+∞Ï·. ∆Ô ¤Ó˙˘ÌÔ Ô˘ ÚÔÂÚ¯fiÙ·Ó ·fi ÙȘ ÌÂÌ‚Ú¿Ó˜ PKU ·ÛıÂÓÒÓ Ì ¯·Ï·Ú‹ ‰›·ÈÙ·, ÌÂÙÚ‹ıËΠ̠ÙËÓ ·ÚÔ˘Û›· ‹ ÙËÓ ·Ô˘Û›· 1,8 mª ∞Ï·. ∏ ̤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞à ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·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˜ ÙÚÔÔÔÈ‹ıËΠ·fi ÙÔÓ Tsakiris (17). OÈ ÔÛÔÙÈÎÔ› ÚÔÛ‰ÈÔÚÈÛÌÔ› ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∆˘Ú Î·È ∞Ï· ¤ÁÈÓ·Ó Ì ·˘ÙfiÌ·ÙÔ ·Ó·Ï˘Ù‹ ·ÌÈÓÔͤˆÓ (Biotronic LC 5001), ¯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) Ì CV (%) 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 Û ∏/À, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙÔ SPSS 10.0 ÛÙ·ÙÈÛÙÈÎfi ·Î¤ÙÔ.
∞ÔÙÂϤÛÌ·Ù· Ÿˆ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔÓ ¶›Ó·Î· 1, ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ 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›·Û οÔÈ· ‰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·È ÙÔ˘ 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 Ì ٷ ›‰· Ù˘ º·È. ™ÙÔÓ ¶›Ó·Î· 3 ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· in vitro ·ÔÙÂϤÛÌ·Ù· Ù˘ ÚÔÂÒ·Û˘ ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∞Ï· ‹ ∞Ï·+º·È ÛÙÔ ÌÂÌ‚Ú·ÓÈÎfi ¤Ó˙˘ÌÔ ∞à ÛÙȘ ÂÚ˘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 ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ Ì·ÚÙ‡ÚˆÓ, Ë ‰Ú·ÛÙÈÎfiÙËÙ· 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¤ÊÂÚ Û ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË Î·Ó¤Ó· ·ÔÙ¤ÏÂÛÌ· (p>0,05). ™˘˙‹ÙËÛË ∏ ›ÛÔ‰Ô˜ ÙˆÓ ·ÌÈÓÔͤˆÓ ‰È·Ì¤ÛÔ˘ ÙÔ˘ ·ÈÌ·ÙÔÂÁÎÂÊ·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˜ ·ÌÈÓÔͤԘ, fiˆ˜ Ù˘ º·È ÛÙËÓ ÔÌ¿‰· µ ÙˆÓ ·ÛıÂÓÒÓ, ·ÚÂÌÔ‰›˙ÂÈ ¿ÏÏ· ·ÌÈÓÔͤ·, fiˆ˜ ÙËÓ ∆˘Ú, Ó· ÂÈÛ¤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·ÙËÚÔ‡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¿‰· ∞ (¡=12) º·È (mg/dl) ∆˘Ú (mg/dl) AÏ· (mg/dl) ¡ÙÔ (Ìmol/l) AX (¢OD/min x mg protein)
·
1,57±0,52 2,09±0,70· 4,07±0,60· 137±29· 3,01±0,18·
OÌ¿‰· µ (¡=11)
ª¿ÚÙ˘Ú˜ (¡=23)
28,45±1,50‚ 0,83±0,30‚ 3,79±1,0‚ 56±18‚ 1,19±0,05‚
1,45±0,60Á 2,13±0,80Á 3,85±1,00Á 142±22Á 3,13±0,16Á
OÈ ÙÈ̤˜ ÂÎÊÚ¿˙ÔÓÙ·È: ª¤ÛË ÙÈÌ‹±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË º·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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¶›Ó·Î·˜ 2. ™˘Û¯ÂÙ›ÛÂȘ ÌÂٷ͇ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ·ÌÈÓÔͤˆÓ º·È, ∆˘Ú, ∞Ï·, Ù˘ ¡ÙÔ Ì ÙË ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞à Û ·ÛıÂÓ›˜ Ì ʷÈÓ˘ÏÎÂÙÔÓÔ˘Ú›· (¡=11)
∞Ã
º·È
∆˘Ú
∞Ï·
¡ÙÔ
-0,58**
+0,44*
+0,12
+0,46*
* p<0,05 ** p<0,01
¡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˜ ›Û˘ ÛÙÔÓ ÔÏÈÎfi ÂÁΤʷÏÔ, ÛÙÔ ‰È¿ÊÚ·ÁÌ· ÔÓÙÈÎÔ‡ (8,9) Î·È ÛÂ Û˘ÁÎÂÎÚÈ̤Ó˜ ÂÚÈÔ¯¤˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ ÔÓÙÈÎÔ‡ (ÚfiÛıÈÔ˜ ÏÔ‚fi˜, ÈfiηÌÔ˜) (24), ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ·Ó·ÛÙÔÏ‹˜ Ù˘ ∞à ·fi ÙË º·È (8,9,24). ∫·Ù¿ Û˘Ó¤ÂÈ·, Ë ‰Ú·ÛÙÈÎfiÙËÙ· 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 ·ÓÙÈÚÔÛˆÂ‡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˘ÁÎÚÈÓfiÌÂÓË Ì ÂΛÓË Ô˘ ÌÂÙÚ‹ıËΠin vitro (20%) ÛÙÔÓ ÂÁΤʷÏÔ Î·È ÛÙÔ ‰È¿ÊÚ·ÁÌ· ÔÓÙÈÎÔ‡, fiˆ˜ ›Û˘ ÛÙÔ Î·ı·Úfi ¤Ó˙˘ÌÔ (8,9), ·ÚÔ˘Û›· ˘„ËÏÒÓ ÂȤ‰ˆÓ º·È. ™˘ÓÂÒ˜, Ë ÌÂÁ¿ÏË ·Ó·ÛÙÔÏ‹ Ù˘ ∞à ÛÙ· ÂÚ˘ıÚÔ·ÙÙ·Ú· ÙˆÓ ·ÛıÂÓÒÓ Ì·˜ ı· ÌÔÚÔ‡Û ӷ ·Ô‰Ôı› ÛÙËÓ Â› Ì·ÎÚfi ¯ÚfiÓÔ Â›‰Ú·ÛË Ù˘ º·È ÛÙË ÌÂÌ‚Ú¿ÓË ÙÔ˘ ÂÓ˙‡ÌÔ˘. ™Â Ì›· ÚfiÛÊ·ÙË ÂÚÁ·Û›· (10) ‰È·ÈÛÙÒıËΠfiÙÈ Ë ∞Ï· ÚÔÊ˘Ï¿ÛÛÂÈ ÙËÓ in vitro ·Ó·ÛÙÔÏ‹ Ù˘ ∞à ·fi ÙË º·È, ·ÓÙ·ÁˆÓÈ˙fiÌÂÓË ÙÔ ·ÚˆÌ·ÙÈÎfi ·˘Ùfi ·ÌÈÓÔ͇ ÙfiÛÔ ÛÙÔÓ 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˙˘ÌÔ ÙˆÓ 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˘ÛÈÔÏÔÁÈÎfi ÙËÓ ·Ó·ÛÙ·Ï̤ÓË ∞Ã ÙˆÓ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ µ. ∆Ô Â‡ÚËÌ· ·˘Ùfi ı· 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›
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¶›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· Î·È º·È+∞Ï· ™˘ÁΤÓÙÚˆÛË (mM)
AX ‰Ú·ÛÙÈÎfiÙËÙ· (¢OD/min x mg protein)
0 1,8 1,8 1,8
3,03±0,13 1,90±0,14*** 2,96±0,21 3,10±0,19
ª¿ÚÙ˘Ú˜ º·È ∞Ï· º·È+∞Ï·
*** p<0,001 OÈ ÙÈ̤˜ ÂÎÊÚ¿˙ÔÓÙ·È: ª¤ÛË ÙÈÌ‹±ÛÙ·ıÂÚ‹ ·fiÎÏÈÛË
Ì·ÎÚfi ¯ÚfiÓÔ Â›‰Ú·ÛË ÙˆÓ ·˘ÍËÌ¤ÓˆÓ ÂȤ‰ˆÓ Ù˘ º·È ÛÙȘ ÂÚ˘ıÚÔ΢ÙÙ·ÚÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ PKU ·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‰Ôı› 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 ·‰ÚÂÓÂÚÁÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ (29), fiˆ˜ ›Û˘ fiÙÈ Ë ¯·ÌËÏ‹ ‰Ú·ÛÙÈÎfiÙËÙ· Ù˘ ∞Ã Û˘Û¯ÂÙ›˙ÂÙ·È ÛÙÂÓ¿ Ì ٷ 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. ∞ÎfiÌË, ı· ÌÔÚÔ‡Û ӷ ÂÚÌËÓ¢ı› Î·È Ô ·Ú·ÙËÚÔ‡ÌÂÓÔ˜ ÙÚfiÌÔ˜ ÛÙÔ˘˜ PKU ·ÛıÂÓ›˜ ¯ˆÚ›˜ ıÂڷ›·, ÏfiÁˆ ·‡ÍËÛ˘ Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ·ÎÂÙ˘Ï¯ÔÏ›Ó˘, ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ÌÂȈ̤Ó˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ ∞Ã. ∂˘¯·ÚÈÛٛ˜ OÈ Û˘ÁÁÚ·Ê›˜ ıˆÚÔ‡Ó ˘Ô¯Ú¤ˆÛ‹ ÙÔ˘˜ Ó· ¢¯·ÚÈÛÙ‹ÛÔ˘Ó ÙËÓ Î·. ∆·ÛÛÔÔ‡ÏÔ˘ ∫·ÏÏÈfiË ÁÈ· ÙËÓ ÂÈÌÂÏË̤ÓË ‰·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 of inherited 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 Ment Defic Res 1988;32:271-281. 3. Burri R, Steffen C, Stieger S, Brodbeck U, Colombo JP, Herschkowitz N. Reduced myelinogenesis and recovery in hyperphenylalaninemic rats. Correlation between brain phenylalanine levels, characteristic brain enzymes for myelination, and brain development. Mol Chem Neuropathol 1990;13:57-69. 4. Francis D. Diets for sick children. 4th ed. Oxford: Blackwell Scientific Publ; 1989. p. 224-255.
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5. Curtius HC, Niederwieser A, Viscontini M, Leimbacher W, Wegmann H, Blehova B et al. Serotonin and dopamine synthesis in phenylketonuria. Adv Exp Med Biol 1981;133:277-291. 6. Krause W, Halminski M, McDonald L, Dembure P, Salvo R, Freides D et al. Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. J Clin Invest 1985;75:40-48. 7. Fernstrom JD. Dietary amino acids and brain function. J Am Diet Assoc 1994;94:71-77. 8. Tsakiris S, Kouniniotou-Krontiri P, Schulpis KH, Stavridis JC. L-phenylalanine effect on rat brain acetylcholine sterase and Na+, K+-ATPase. Z Naturforsch 1998;53c:163-167. 9. Tsakiris S, Kouniniotou-Krontiri P, Schulpis KH. Lphenylalanine effect on rat diaphragm acetylcholinesterase and Na+, K+-ATPase. Z Naturforsch 1998;53c: 1055-1060. 10. Tsakiris S, Schulpis KH. Alanine reverses the inhibitory effect of phenylalanine on acetylcholinesterase activity. Z Naturforsch 2002;57c:506-511. 11. Hawkins CA, Greenfield SA. Non-cholinergic action of exogenous 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 phenylketonuric patients on a “loose diet”. Clin Endocrinol 1998; 48:99-101. 13. Galbraith DA, Watts DC. Changes in some cytoplasmic enzymes from red cells fractionated into age groups by centrifugation in Ficoll/Triosil gradients. Biochem J 1980;191:63-70. 14. Kamber E, Poyiagi A, Deliconstantinos G. Modifications in the activities of membrane-bound enzymes during in vivo ageing of human and rabbit erythrocytes. Comp Biochem Physiol 1984;77B:95-99. 15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-275. 16. Ellman GL, Courtney D, Andres V, Featherstone RM. A new a rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88-85. 17. Tsakiris S. Effects of L-phenylalanine on acetylcholinesterase and Na+, K+-ATPase activities in adult and aged rat brain. 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. J Chromatogr 1993;617:304-307.
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19. Carlson HE, Hyman DB, Blitzer MG. Evidence for an intracerebral action of phenylalanine in stimulation of prolactin 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 in erythrocyte membranes from patients with phenylketonuria. Pediatr Res 2001;50:56-60. 21. Bogdanski DF, Tissari A, Brodie BB. Role of sodium, potassium, ouabain and reserpine in uptake, storage and metabolism of biogenic amines in synaptosomes. Life Sci 1968;7:419-428. 22. Swann AC. (Na+, K+)-adenosine triphosphatase regulation by the sympathetic nervous system: effects of noradrenergic stimulation and lesion in vivo. J Pharmacol Exp Ther 1984;228:304-311. 23. Meyer EM, Cooper JR. Correlations between Na+, K+ATPase activity and acetylcholine release in rat cortical synaptosomes. J Neurochem 1981;36:467-475. 24. Doulgeraki A, Papadopoulou-Daifoti Z, Tsakiris S. Effects of L-phenylalanine on acetylcholinesterase and Na+, K+ATPase activities in suckling rat frontal cortex, hippocampus and hypothalamus. Z Naturforsch 2002;57c:182188. 25. Weil-Maiherbe F. Blood adrenaline and intelligence. J Ment Sci 1995;101:733-754. 26. Antonas KN, Coulson WF. Brain uptake and protein incorporation of amino acids studied in rats subjected to prolonged hyperphenylalaninaemia. J Neurochem 1975; 25:309-314. 27. Taub F, Johnson TC. The mechanism of polyribosome disaggregation in brain tissue by phenylalanine. Biochem J 1975;151:173-180. 28. Hughes JV, Johnson TC. The effect of hyperphenylalaninaemia on the concentrations of aminoacyl-transfer ribonucleic acid in vivo. Biochem J 1977;162:527-537. 29. Ohno M, Kobayashi M, Kishi A, Watanabe S. Working memory failure by combined blockade of of muscarinic and ‚-adrenergic transmission in the rat hippocampus. Neuroreport 1997;8:1571-1575.
HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 18-06-2002 HÌÂÚÔÌËÓ›· ¤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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∂ƒ∂À¡∏∆π∫∏ ∂ƒ°∞™π∞
Paediatriki 2003;66:118-127
ORIGINAL ARTICLE
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
¶ÂÚ›ÏË„Ë: ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ÛÙËÓ ∂ÏÏ¿‰·, Ë ÂÚÁ·ÛÙËÚȷ΋ ‰ÈÂÚ‡ÓËÛË ÙˆÓ ÎÏËÚÔÓÔÌÈÎÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ (∫ª¡) ‰È¢ڇÓÂÙ·È. ∆· ∫ª¡ ÔÊ›ÏÔÓÙ·È Û ÁÂÓÂÙÈο ηıÔÚÈ˙fiÌÂÓ˜ ÂÓ˙˘ÌÈΤ˜ ‹ ¿ÏϘ ÚˆÙÂ˚ÓÈΤ˜ ·Ó¿ÚÎÂȘ ‚ÈÔ¯ËÌÈÎÒÓ ·ÓÙȉڿÛÂˆÓ 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·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, ÂӉȿÌÂÛ· ÚÔ˚fiÓÙ· ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ·ÌÈÓÔͤˆÓ, ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ Î·È ÙˆÓ ˘‰·Ù·ÓıڿΈÓ. OÈ ·ÛıÂÓ›˜ ·˘ÙÒÓ ÙˆÓ ·Ó·ÚÎÂÈÒÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂȉÈΤ˜ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ Ì ¯·Ú·ÎÙËÚÈÛÙÈ΋ ·¤ÎÎÚÈÛË ÔÚÁ·ÓÈÎÒÓ 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·ÓÈÎÒÓ ÔͤˆÓ ·ÔηχÙÂÈ ÙÔÓ Ù‡Ô Ù˘ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜. ∆ËÓ ÂÚ›Ô‰Ô 1996-2001 ·Ó·Ï‡ıËÎ·Ó Ì ÚÔÙ˘ÔÔÈË̤ÓË ÌÂıÔ‰ÔÏÔÁ›· GC-MS, ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ ·fi 5021 ·ÛıÂÓ›˜ Ì ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›· 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 inherited defects of organic acid metabolism is a continuously expanding diagnostic procedure in Greece. The diagnosis of the organic acidurias, a high incidence group of inborn errors of metabolism (IEM), is based primarily on identification of the organic acid profile in the urine and/or acylcarnitine profile abnormalities in the blood using gas chromatography-mass spectrometry (GC-MS) and tandem mass spectrometry respectively. The in time diagnosis of the majority of these disorders is critical for early initiation of effective treatment and improved prognosis. The last six years, urine and blood specimens of 5021 patients at high risk for IEM, in particular defects of organic acid metabolism, were investigated in the Clinical Biochemistry Laboratory of the “P. & A. Kyriakou” Children’s Hospital. IEM were diagnosed in 85 patients, specifically, MMA (8), propionic acidemia (3), glutaric aciduria type I (6), SSADH (6), L-2hydroxy-glutaric aciduria (4), Canavan disease (2), HMGlyase deficiency (2), ‚-ketothiolase deficiency (1), EPEMA syndrome (1), MADD (1), MCAD deficiency (7) and 5 cases with dicarboxylic aciduria and abnormal acylcarnitine profile analyses. Thirteen patients presented with toxic hyperammonemia (6 cases of OTC, 1 of ASS, 4 of LPI 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 Aristotelion University, 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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Paediatriki 2003;66:118-127
˘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 ·ÛıÂÓ›˜). ∞ÌÈÓÔ-ÔÍ˘Ô¿ıÂÈ· (·ÏηÙÔÓÔ˘Ú›·, ÓfiÛÔ˜ Ì ÔÛÌ‹ Ô‡ÚˆÓ Û·Ó ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘, Ù˘ÚÔÛÈÓ·ÈÌ›· Ù‡Ô˘ π) ›¯·Ó 10 ·ÛıÂÓ›˜. O ·ÚÈıÌfi˜ ·˘ÙÒÓ ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ, Ô ÔÔ›Ô˜ ·ÓÙÈÛÙÔȯ› Û ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ· 1:8696 ÁÂÓÓ‹ÛÂȘ Ù˘ Û˘ÁÎÂÎÚÈ̤Ó˘ ÂÚÈfi‰Ô˘ ÛÙË ¯ÒÚ·, ·ÔÙÂÏ› ¤Ó·Ó ÚÒÙÔ ‰Â›ÎÙË Ù˘ ¤ÎÊÚ·Û‹˜ ÙÔ˘˜ ÛÙÔÓ ÂÏÏËÓÈÎfi 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·È Ì ¿ÏϘ Ù¯ÓÈΤ˜. ∞Ó¢Ú‡ıËÛ·Ó 2 ·ÛıÂÓ›˜ Ì ·Ó¿ÚÎÂȘ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ Ô˘ÚÈÓÒÓ Î·È ÙˆÓ ˘ÚÈÌȉÈÓÒÓ Î·È 14 ·ÛıÂÓ›˜ Ì ÂÓ˙˘ÌÈΤ˜ ·Ó¿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· ˘ÚÔÛÙ·Ê˘ÏÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘ Û 4 ·ÛıÂÓ›˜). ∞ÎfiÌË, Û 247 ·ÛıÂÓ›˜ (5,3% ÙˆÓ ·Ó·Ï‡ÛˆÓ), ÛÙÔ Ê¿ÛÌ· ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ‰È·ÈÛÙÒıËÎ·Ó ÂÓ‰ÂÈÎÙÈΤ˜ Î·È fi¯È ‰È·ÁÓˆÛÙÈΤ˜ ‰È·Ù·Ú·¯¤˜. ™ÙË ÌÂϤÙË ·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·ÎÙËÚÈÛÙÈο ¯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¯Ô ÙË ‚ÂÏÙ›ˆÛË Ù˘ ‰È¿ÁÓˆÛ˘ ·ÛıÂÓÒÓ Ì ÎÏËÚÔÓÔÌÈΤ˜ ÔÚÁ·ÓÈΤ˜ ÔÍ˘Ô˘Ú›Â˜ ÛÙËÓ ∂ÏÏ¿‰·.
patients had an amino acid disorder, namely, alkaptonuria (5), MSUD (3), tyrosinemia type I (2), and one patient had a pyrimidine disorder (DPD deficiency). These diagnoses indicate that the cumulative incidence of these disorders in Greece could be greater than 1:8696 births. In addition, 14 patients with primary lactic metabolic acidosis were identified and one with abnormalities of purine metabolism. Evaluation of the data shows a rather low diagnostic rate (about 1.67% of the patients studied). In addition to the specific diagnoses, significant urine organic acid abnormalities were found in 247 cases, with no defined cause. The main clinical symptoms of the patients examined were neurological disturbances, accounting for 63.3% of patients, the majority of which presented with indicative findings of chronic encephalopathy, and 4.3% with acute encephalopathy. Developmental delay and dysmorphic features were present in the 8.7% of the patients and organ failure in 26.4%. The clinical and laboratory findings of this study are presented with a view to increasing the awareness of the practicing pediatrician and improving healthcare planning in Greece to ensure effective diagnosis.
§¤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.
Key words: inborn errors of metabolism, organic acidurias, metabolic decompensation, gas chromatography-mass spectrometry.
∂ÈÛ·ÁˆÁ‹ ∆· ÎÏËÚÔÓÔÌÈο ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· (∫ª¡Inherited metabolic disorders) ·ÔÙÂÏÔ‡Ó ÌÂÁ¿ÏË Î·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˘ ÓÔÛËÚfiÙËÙ·˜ 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·ÙËÁÔÚ›· ÙˆÓ Û¿ÓÈˆÓ ÓÔÛËÌ¿ÙˆÓ (rare disorders or orphan diseases) (3). ¶·Ú’ fiÏ· ·˘Ù¿, Ë ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ¿ ÙÔ˘˜ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, Û‡Ìʈӷ Ì ‰È¿ÊÔÚ˜ ÌÂϤÙ˜, Â›Ó·È ÌÂٷ͇ 1:600-2000 ÁÂÓÓ‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ (3-5). OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÙÔ˘˜ ÔÊ›ÏÔÓÙ·È Û ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ (inborn errors of metabolism), ÔÈ Ôԛ˜ ÚÔηÏÔ‡ÓÙ·È ·fi Û˘ÁÎÂÎÚÈ̤Ó˜ ÂÓ˙˘ÌÈΤ˜ ·Ó¿ÚÎÂȘ ‹ ·fi ÙË Û‡ÓıÂÛË ÂÏ·Ùو̷ÙÈ΋˜ ‰ÔÌ‹˜ Î·È ÏÂÈÙÔ˘ÚÁ›·˜ ÚˆÙÂ˚ÓÒÓ (6). ∞›ÙÈÔ ·˘ÙÒÓ ÙˆÓ ·Ó·ÚÎÂÈÒÓ Â›Ó·È Û˘ÁÎÂÎÚÈ̤Ó˜ ÌÔÓÔÁÔÓȉȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ (Mendelian
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inheritance, single-gene defects), ‚¿ÛÂÈ ÙˆÓ ÔÔ›ˆÓ Î·È Ù·ÍÈÓÔÌÔ‡ÓÙ·È ¤Ú·Ó Ù˘ ÎÏÈÓÈ΋˜ ÙÔ˘˜ ·Ó·ÊÔÚ¿˜ (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΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·). ∏ ‰È·ÁÓˆÛÙÈ΋ ‰ÈÂÚ‡ÓËÛ‹ ÙÔ˘˜ Â›Ó·È Û˘¯Ó¿ ‰˘Û¯ÂÚ‹˜ Î·È ÚÔÛÂÁÁ›˙ÂÙ·È Ì ·ÏÏËÏÔ˘¯›· ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ·Ó·Ï‡ÛˆÓ. ™Ù· ÂÚÈÛÛfiÙÂÚ· ÓÔÛ‹Ì·Ù·, Ë ‰È¿ÁÓˆÛË ÙÂÎÌËÚÈÒÓÂÙ·È Ì ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi Ù˘ ÂÓ˙˘ÌÈ΋˜ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÙÔ˘ ÂÏÂÁ¯fiÌÂÓÔ˘ ÂÓ˙‡ÌÔ˘ ‹ Ù˘ ·Ó›¯Ó¢Û˘ Ù˘ ÚˆÙÂ˚ÓÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Î·È Ù˘ ·Ó‡ÚÂÛ˘ Ù˘ ˘Â‡ı˘Ó˘ ÁÔÓȉȷ΋˜ ÌÂÙ¿ÏÏ·Í˘. ™Â Ï›Á˜ ÂÚÈÙÒÛÂȘ, Ë ÁÔÓȉȷ΋ ÌÂÙ¿ÏÏ·ÍË Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙÔÓ ÎÏÈÓÈÎfi Î·È ‚ÈÔ¯ËÌÈÎfi Ê·ÈÓfiÙ˘Ô ÙˆÓ ÓÔÛËÌ¿ÙˆÓ (6). ∆· ∫ª¡ Ô˘ ÔÊ›ÏÔÓÙ·È Û ·Ó¿ÚÎÂÈ· ÙÔ˘ ÌÂÙ·‚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¿ÙˆÓ ÛËÌ·ÓÙÈ΋˜ Û˘¯ÓfiÙËÙ·˜ Î·È ÂȉÈÎÒÓ ÎÏÈÓÈÎÒÓ ÂΉËÏÒÛˆÓ. ÷ڷÎÙËÚ›˙ÔÓÙ·È ·fi ÙËÓ ·Ú·ÁˆÁ‹ Î·È ·¤ÎÎÚÈÛË ÌÂÁ¿ÏˆÓ Û˘ÁÎÂÓÙÚÒÛÂˆÓ Î·Ú‚Ô͢ÏÈÎÒÓ ÔͤˆÓ. ∂ÈÚfiÛıÂÙ· ÙˆÓ ·ÓˆÙ¤Úˆ ÎÏ·ÛÈο ÔÚÈ˙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 ¤¯ÂÈ ‰È·ÁÓˆÛÙÈ΋ ·Í›·. ™¯ÂÙÈο ·Ó·Ê¤ÚÔÓÙ·È ·Ó¿ÚÎÂȘ ÙÔ˘ ÂӉȿÌÂÛÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ·ÌÈÓÔͤˆÓ, Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ, ÙˆÓ ˘‰·Ù·ÓıڿΈÓ, ÙˆÓ ‚ÈÙ·ÌÈÓÒÓ, ÙˆÓ ˘ÚÈÌȉÈÓÒÓ, ÙˆÓ Ó¢Úԉȷ‚È‚·ÛÙÒÓ, ÙˆÓ ÈÛÔÚÂÓÔÂȉÒÓ Î·È Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘. ™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·‚ÔÏÈÎÒÓ ÚÔ˚fiÓÙˆÓ Ù˘ ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ‹ ÛÙËÓ ¤ÏÏÂÈ„Ë Ù˘ ·Ú·ÁˆÁ‹˜ ÂÓÂÚÁÂÈ·ÎÒÓ ˘ÔÛÙڈ̿وÓ. ¶·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˘ÚÁ›Â˜ Î·È ˘ÚÔ‰ÔÙÔ‡Ó ÛÔ‚·Ú¤˜ ÎÏÈÓÈΤ˜ ‰È·Ù·Ú·¯¤˜ (6). OÈ ÂÓ ÏfiÁˆ ÂÓ˙˘ÌÈΤ˜ ·Ù¤ÏÂȘ ÌÂÙ·‚È‚¿˙ÔÓÙ·È Ì ÙÔÓ ˘ÔÏÂÈfiÌÂÓÔ ÛˆÌ·ÙÈÎfi ¯·Ú·ÎÙ‹Ú· Î·È ÔÚÈṲ̂Ó˜ ÌÂ Ê˘ÏÔÛ‡Ó‰ÂÙÔ ˘ÔÏÂÈfiÌÂÓÔ. ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÔÚÁ·ÓÈÎÒÓ Ô͢ԢÚÈÒÓ Â›Ó·È ·ıÚÔÈÛÙÈο ÛËÌ·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 Ô͢ԷıÂÈÒÓ Â›Ó·È Û¯ÂÙÈο ¢¯ÂÚ‹˜ Ì ÙË ¯Ú‹ÛË ÙˆÓ Ù¯ÓÈÎÒÓ Ù˘ ·¤ÚÈ·˜ ¯ÚˆÌ·ÙÔÁÚ·Ê›·˜-Ê·ÛÌ·ÙÔÁÚ·Ê›·˜ Ì·˙ÒÓ (GC-MS), ΢ڛˆ˜ Ì ÙËÓ ·Ó¿Ï˘ÛË ‰Â›ÁÌ·-
120
Paediatriki 2003;66:118-127
ÙÔ˜ Ô‡ÚˆÓ ÙˆÓ ·ÛıÂÓÒÓ (11). ¶¿Óˆ ·fi 65 ‰È·ÁÓˆÛÙÈο 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 ÂȉÈΤ˜ Ù¯ÓÈΤ˜ ·Ó¿Ï˘Û˘ ÙˆÓ Û˘Ó‰Â‰ÂÌ¤ÓˆÓ Ì ÁÏ˘Î›ÓË ‹ 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 ÎÏÈÓÈÎÒÓ ÂΉËÏÒÛÂˆÓ ÙˆÓ ·ÛıÂÓÒÓ, ‰Â›ÁÌ·Ù· ÙˆÓ ÔÔ›ˆÓ ÂÍÂÙ¿ÛÙËÎ·Ó ÛÙÔ ÂÚÁ·ÛÙ‹ÚÈÔ, ‚) Ë ·ÚÔ˘Û›·ÛË ÙˆÓ ‰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˘, Ì ÂÈÏÂÎÙÈ΋ ‰ÈÂÚ‡ÓËÛË, Ù· Â˘Ú‹Ì·Ù· ÙˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ ÙÔ˘ ·›Ì·ÙÔ˜ (14) Î·È Á) Ë ·Ú¿ıÂÛË ÛÙÔȯ›ˆÓ Î·È ÂÌÂÈÚÈÎÒÓ ·Ú·ÙËÚ‹ÛÂˆÓ Ô˘ ‰È¢ÎÔχÓÔ˘Ó ÙËÓ ÎÏÈÓÈ΋ Î·È ÂÚÁ·ÛÙËÚȷ΋ ÚÔÛ¤ÁÁÈÛË ÙˆÓ ÓÔÛËÌ¿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 Û 311 ·ÛıÂÓ›˜ (9,31%), 2 ÌËÓÒÓ Ì¤¯ÚÈ 2 ÂÙÒÓ Û 1326 ·ÛıÂÓ›˜ (39,7%), 2-6 ÂÙÒÓ Û 936 ·ÛıÂÓ›˜ (28%), ÂÓÒ 769 ·ÛıÂÓ›˜ (23%) ›¯·Ó ËÏÈΛ· ¿Óˆ ·fi 6 ÂÙÒÓ. ¶ÔÛÔÛÙfi 10,6% ÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó ÌÂÙ·Ó¿ÛÙ˜. ™ÙÔ Û˘Óԉ¢ÙÈÎfi ÂÓËÌÂÚˆÙÈÎfi 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˜ Û 2240 ·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˜ Û 55 ·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·¤ÌÊıËÎ·Ó ÁÈ· ÙË ‰ÈÂÚ‡ÓËÛË ÛËÌ·ÓÙÈÎÒÓ ‚ÈÔ¯ËÌÈÎÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ. ¶ÔÏ˘Û˘ÛÙËÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ ·Ó·Ê¤ÚÔÓÙ·È Û 176 ·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¿ÓÈÛË Ù˘ ·‰Ú‹˜ ÌÂÙ·‚ÔÏÈ΋˜ ‰È·Ù·Ú·¯‹˜, ˘ÔÁÏ˘Î·ÈÌ›·˜, ˘ÂÚ·Ì̈ÓÈ·ÈÌ›·˜, ΤوÛ˘ ‹ ÌÂÙ·‚ÔÏÈ΋˜ ÔͤˆÛ˘. ∞fi
MARC-APR 03
14-05-03
14:48
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¶·È‰È·ÙÚÈ΋ 2003;66:118-127
Paediatriki 2003;66:118-127
¶›Ó·Î·˜ 1. ∫ÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ·ÛıÂÓÒÓ Ô˘ ÂÍÂÙ¿ÛÙËÎ·Ó ÁÈ· ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· ¢È·Ù·Ú·¯¤˜ ÙÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ∞ÛıÂÓ›˜
2240 (63,3%)
∞.1) ∂ΉËÏÒÛÂȘ ¯ÚfiÓÈ·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ 2086 æ˘¯ÔÎÈÓËÙÈ΋ ηı˘ÛÙ¤ÚËÛË 914 ™·ÛÌÔ› 760 ¶ÚÔ‚Ï‹Ì·Ù· ÔÌÈÏ›·˜ 67 ¢È·Ù·Ú·¯¤˜ Û˘ÌÂÚÈÊÔÚ¿˜/·˘ÙÈÛÌfi˜ 67/46=113 ¡ÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË 93 ª·ÎÚÔÎÂÊ·Ï›· 72 ªÈÎÚÔÎÂÊ·Ï›· 45 À‰ÚÔΤʷÏÔ˜ 24 ∂ÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË 126 ∞Ù·Í›·/‰˘ÛÙÔÓ›· 128/18=146 ÀÂÚÙÔÓ›·/ÙÚfiÌÔ˜ 64/21=85 ÀÔÙÔÓ›· 246 ∞.2) OÍ›· ÂÁÎÂÊ·ÏÔ¿ıÂÈ· 154 (4,3%) ∫ÒÌ·, Ï‹ı·ÚÁÔ˜ 86 ¢È·Ù·Ú·¯‹ ÂȤ‰Ô˘ Û˘Ó›‰ËÛ˘, ¿ÓÔȘ 68 B) ¢˘ÛÌÔÚʛ˜ 55 ·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 ˘fi ÂÏÂÁ¯fiÌÂÓ˜ Û˘Óı‹Î˜. ¶·ÚÂÏ‹ÊıËÛ·Ó Ô‡Ú· ·ÛıÂÓÒÓ 2-6 ÒÚ˜ 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 Ù¯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· ËÌÈÔÛÔÙÈο ‚¿ÛÂÈ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙˆÓ Ô‡ÚˆÓ (mmol/mol ÎÚ·ÙÈÓ›Ó˘) Ì ÙË ¯Ú‹ÛË ÂÛˆÙÂÚÈÎÔ‡ ÚÔÙ‡Ô˘ Ô˘Û›·˜. ∏ ·Ó¿Ï˘ÛË ¤ÁÈÓ Û ·Ó·Ï˘Ù‹ Ù‡Ô˘ Carlo-Elba 2000, Fison’s MD800, Ù¯ÓÈ΋ ¤Á¯˘Û˘ splitless, Ù‡Ô˜ ÈÔÓÈÛÌÔ‡ electron-impact Î·È ¯Ú‹ÛË ÛÙ‹Ï˘ ¯ÚˆÌ·ÙÔÁÚ·Ê›·˜ Ù‡Ô˘ BP-1 ‹ BP-5. ™Â 122 ·ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈο ÎÏÈÓÈο ‹ ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ‹ ·Ó¿ÚÎÂÈ·˜ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ, ÂÍÂÙ¿ÛÙËΠÙÔ Ê¿ÛÌ· ÙˆÓ Û˘Ó‰Â‰ÂÌ¤ÓˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ (acyl-carnitine profile) ·fi ÛÙ·ÁfiÓ˜ ÍËÚÔ‡ ·›Ì·ÙÔ˜ Ì ÙË ÌÂıÔ‰ÔÏÔÁ›· (16) Tandem-MS (Û‡ÛÙËÌ· ‰‡Ô Ê·ÛÌ·ÙÔÁÚ¿ÊˆÓ Ì·˙ÒÓ), ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÂȉÈο ÂÚÁ·ÛÙ‹ÚÈ· ÙÔ˘ Â͈ÙÂÚÈÎÔ‡. ∏ ÙÂÏÈ΋ ÙÂÎÌËÚ›ˆÛË ÙÔ˘ ˘Â‡ı˘ÓÔ˘ ÂÓ‰ÔÁÂÓÔ‡˜ ÌÂÈÔÓÂÎÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ¤ÁÈÓ Ì ÙË Ì¤ÙÚËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ 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-
¢˘ÛÏÂÈÙÔ˘ÚÁ›Â˜ ÔÚÁ¿ÓˆÓ ∞ÛıÂÓ›˜
1299 (36,7%)
°.1) ¶ÚÔÂÍ¿Ú¯Ô˘Û˜ ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜ ∏·ÙÔÌÂÁ·Ï›·/Ë·ÙÈ΋ ‚Ï¿‚Ë ª˘˚Îfi ∞Ó·Ó¢ÛÙÈÎfi ª˘ÔηډÈÔ¿ıÂÈ·/ηډȷΤ˜ ·ÓˆÌ·Ï›Â˜ ∞ÈÌÔÔÈËÙÈÎfi ∂Ó‰ÔÎÚÈÓÔÏÔÁÈÎfi ¡ÂÊÚ¿ ¶ÂÙÈÎfi/ÏÔÈÌÒÍÂȘ ¢¤ÚÌ·/ÙÚ›¯Â˜ ŸÚ·ÛË ∞ÎÔ‹ ™Ï‹Ó·˜ ¶¿ÁÎÚ·˜ OÛÙ¿ °.2) ¢˘ÛÙÚÔÊ›·, ÛÙ·ÛÈÌfiÙËÙ· ‚¿ÚÔ˘˜ °.3) ªÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜
935 (26,4%) 78/95=173 73 51 56/24=80 62 25 70 206 24 61 40 36 13 21 309 (8,7%) 260 (7,3%)
ο ·ÛıÂÓ›˜, Û 10 ÂÎ ÙˆÓ ÔÔ›ˆÓ, fï˜, Ë ‰È¿ÁÓˆÛË 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·ÈÛÙÒıËÎ·Ó Û 65 ·ÛıÂÓ›˜, 16 ‰È·ÊÔÚÂÙÈΤ˜ ÂÓ˙˘ÌÈΤ˜ ‹ 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·Î·˜ 2, ÓÔÛ‹Ì·Ù· 5-9, 13-15). ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ÂΉ‹ÏˆÓ·Ó Û˘Ìو̷ÙÔÏÔÁ›· ÛÙ· Ï·›ÛÈ· ÙˆÓ ÎÏÈÓÈÎÒÓ Ê·ÈÓÔÙ‡ˆÓ ÙˆÓ ·ÓÙ›ÛÙÔȯˆÓ ÓÔÛËÌ¿ÙˆÓ. ∏ ÂÓ˙˘ÌÈ΋ ‹/Î·È Ë ÁÔÓȉȷ΋ Ù·˘ÙÔÔ›ËÛË ÙˆÓ ·Ó·ÚÎÂÈÒÓ Ù˘ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ¤ÁÈÓ Û ÙÔ˘Ï¿¯ÈÛÙÔÓ 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-˘‰ÚÔ͢ÁÏÔ˘Ù·ÚÈ΋˜ Ô͢Ԣڛ·˜ Î·È Âı˘ÏÔÌ·ÏÔÓÈ΋˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜, ÛÙ· ÔÔ›· ‰ÂÓ ¤¯ÂÈ Ù·˘ÙÔÔÈËı› ˘Â‡ı˘ÓË ·Ó¿ÚÎÂÈ· ÂÓ˙‡ÌÔ˘, ÚˆÙ½Ó˘ ‹ ÁÔÓȉȷ΋˜ ÌÂÙ¿ÏÏ·Í˘, Ë ÓfiÛÔ˜ ÂȂ‚·ÈÒıËΠ̠ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ Ô‡ÚˆÓ Î·È ·fi ¿ÏÏÔ ÂÍÂȉÈÎÂ˘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˘, Â˘Ú‹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 ‰Â›ÁÌ·Ù· ‚ÈÔ„›·˜ Ì˘fi˜ ‹ ‰¤ÚÌ·ÙÔ˜ ·˘ÙÒÓ ÙˆÓ ·ÛıÂÓÒÓ, ÂȂ‚·›ˆÛÂ Î·È Ù·˘ÙÔÔ›ËÛÂ Û˘ÁÎÂÎÚÈ̤ÓË 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
121
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·122
¶·È‰È·ÙÚÈ΋ 2003;66:118-127
Paediatriki 2003;66:118-127
¶›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· 1. ∞ÏηÙÔÓÔ˘Ú›· 2. ÀÂÚ·Ì̈ÓÈ·ÈÌ›·, ÔÚÔÙÈ΋ Ô͢Ԣڛ· O∆C deficiency ASS deficiency LPI disorder 3. MSUD 4. T˘ÚÔÛÈÓ·ÈÌ›· (π) 5·. MMA mut 5‚. Adocbl(A) 6. ¶ÚÔÈÔÓÈ΋ Ô͢Ԣڛ· 7. HMGlyase-deficiency 8. ‚-ÎÂÙÔıÈÔÏ¿ÛË 9. °ÏÔ˘Ù·ÚÈ΋ Ô͢-(I) 10. Canavan disease 11. SSADH-deficiency 12. L-2-OH-GA 13. MADD 14. MCAD 15. EPEMA syndrome ¢È·Ù·Ú·¯¤˜, DCA+AC+ηÚÓÈÙ›Ó˘ ™‡ÓÔÏÔ °·Ï·ÎÙÈ΋ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË 16. DPD deficiency ¢È·Ù·Ú·¯¤˜ Ô˘ÚÈÓÒÓ ™‡ÓÔÏÔ
∞ÛıÂÓ›˜
∂Ȃ‚·›ˆÛË ÓfiÛÔ˘
∂Ó ˙ˆ‹
∞‚›ˆÛ·Ó
∂Ó˙˘ÌÈ΋ ·Ó¿ÚÎÂÈ·
°ÔÓȉȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ
5 10 (5+2*) (1) (2) 3 1 7 0 2+1** 2 1 4 2 6 3 1 6 1 5 59 14 1 1 75
1 2 0 1 1 1 0 0 2 0 0 1 0 1 0 0 10 0 0 0 10
2 2 4 3 1 2 1 1 2 1 6 2 5 2 0 6 1 -
3 4 1 0 0 1 2 2 0 0 0 0 0 0 1 0 0 -
5 1 3 1 4 1 3 2 1 3 2 5 1 0 ∂ÚÂ˘Ó¿Ù·È -
2 1 4 ™Â ÂͤÏÈÍË 2 5 0 7 -
1 42
0 1 15
12 1 45
1 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
¤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‰ÂÈÎÙÈο ·Ó¿ÚÎÂÈ·˜ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ ÛÙ· ÌÈÙÔ¯fiÓ‰ÚÈ·. ∞˘ÙÔ› ÔÈ ·ÛıÂÓ›˜, ›Û˘ ·ÚÔ˘Û›·Û·Ó ‰ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ· Î·È ÌÂȈ̤ÓË 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¿ÚÎÂÈ·. ™Â ¿ÏÏÔ˘˜ 5 ·ÛıÂÓ›˜, Ë ·‡ÍËÛË ÙˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ ÙÔ˘ ·›Ì·ÙÔ˜ ‰ÂÓ ‰È¢ÎÚÈÓ›ÛÙËΠ̠ÂÚ·ÈÙ¤Úˆ ·Ó·Ï‡ÛÂȘ. ∂›Û˘, Ë ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ·Ó¤‰ÂÈÍ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ›‰Ô˘˜ ηÈ
122
Ù˘ Û˘ÁΤÓÙÚˆÛ˘ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Û 247 ·ÛıÂÓ›˜ (5,3% ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ) (¶›Ó·Î·˜ 3), ÛÙÔ˘˜ ÔÔ›Ô˘˜ Ô Â·Ó¤ÏÂÁ¯Ô˜ Î·È Ë ‰ÈÂÚ‡ÓËÛË Èı·Ó‹˜ ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ∫ª¡ ‰ÂÓ ÚÔ¯ÒÚËÛ ÂÚ·ÈÙ¤Úˆ. OÈ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÛÙȘ ηÙËÁÔڛ˜ ∞.1, µ Î·È °.2 ÛÙÔÓ ¶›Ó·Î· 1 ·Ó·Ê¤ÚÔÓÙ·È Û ̷ÎÚÔ¯ÚfiÓÈ· ‰È¿ÚÎÂÈ· Ù˘ ÓfiÛÔ˘ (>6 Ì‹Ó˜). OÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÔÙÂÏÔ‡Ó ¿Óˆ ·fi ÙÔ 60% ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË. ∏ ‰ÈÂÚ‡ÓËÛË Ô˘ ¤ÁÈÓ Û ·˘Ù‹ ÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ ·ÔÎ¿Ï˘„ 27 ·ÛıÂÓ›˜ ·fi ÙÔ˘˜ 85 Ì ‰È·ÁÓˆÛÙÈ΋ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·. ™Ô‚·Úfi Ô͇ ÌÂÙ·‚ÔÏÈÎfi ÂÂÈÛfi‰ÈÔ, ÔÍ›· ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ‹ ÔÍ›· ÔÚÁ·ÓÈ΋ ‚Ï¿‚Ë, ÂΉËÏÒÛÂȘ
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·123
¶·È‰È·ÙÚÈ΋ 2003;66:118-127
Ô˘ ΢ڛˆ˜ ·Ó·Ê¤ÚÔÓÙ·È ÛÙȘ ηÙËÁÔڛ˜ ∞.2, °.1, °.3, ·ÚÔ˘Û›·Û·Ó 908 ·ÛıÂÓ›˜ (25% ÙˆÓ ·Ó·ÊÂÚÔ̤ӈÓ). ∞fi ÙË ‰ÈÂÚ‡ÓËÛË ·˘Ù‹˜ Ù˘ ÔÌ¿‰·˜ ÂΉËÏÒÛˆÓ, ‰È·ÈÛÙÒıËΠ‰È·ÁÓˆÛÙÈ΋ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· Û 51 ·ÛıÂÓ›˜. ∏ ‰È¿ÎÚÈÛË Î·È Ù·ÍÈÓfiÌËÛË 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›· ÂΉËÏÒÛˆÓ. π‰È·›ÙÂÚË ·Í›· ¤¯Ô˘Ó Ù· ÛÙÔȯ›· Ù˘ ÔÚ›·˜ ÙˆÓ ·ÛıÂÓÒÓ ÌÂÙ¿ ÙË ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘. ∞‚›ˆÛ·Ó 15 ·ÛıÂÓ›˜, 6 ÂÎ ÙˆÓ ÔÔ›ˆÓ ηٿ ÙËÓ ÂÚ›Ô‰Ô ÙÔ˘ ÚÒÙÔ˘ ÂÂÈÛÔ‰›Ô˘ Ù˘ ÓfiÛÔ˘. OÈ 23 ·fi ÙÔ˘˜ 42 ˙ÒÓÙ˜ ·ÛıÂÓ›˜ Ì ÁÓˆÛÙ‹ ÎÏÈÓÈ΋ ÔÚ›· ·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˘ ÛÙË ¯ÒÚ·. ¢Â‰Ô̤ÓÔ˘ fiÙÈ Ë ‰ÈÂÚ‡ÓËÛË ÁÈ· Èı·Ó‹ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ· Ú·ÁÌ·ÙÔÔÈ‹ıËΠϋڈ˜ ÌfiÓÔ ·fi ÙË Û˘ÁÎÂÎÚÈ̤ÓË ÔÌ¿‰· ÛÙËÓ ∂ÏÏ¿‰·, ÙÔ Ì¤ÁÂıÔ˜ ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ Â›Ó·È ÂÓ‰ÂÈÎÙÈÎfi ÁÈ· ÙËÓ ÂÍ·ÁˆÁ‹ ¯Ú‹ÛÈÌˆÓ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ. ŒÙÛÈ, ÔÈ ·Ó·ÊÂÚfiÌÂÓ˜ ‰ÈÂÚ¢ӋÛÂȘ ˘ÔÏ›ÔÓÙ·È ÙÔ˘ ÔÛÔÛÙÔ‡ ÙˆÓ ·ÛıÂÓÒÓ Ì ÎÏËÚÔÓÔÌÈο ÓÔÛ‹Ì·Ù· Ô˘ ÔÊ›ÏÔÓÙ·È Û ÌÔÓÔÁÔÓȉȷΤ˜ ·Ó¿ÚÎÂȘ (1% ÙˆÓ ÁÂÓÓ‹ÛˆÓ) (2). ÕÏψÛÙÂ, ÔÏÏÔ› ·ÛıÂÓ›˜ Ì ∫ª¡, ·ÏÏ¿ Î·È ¿Û¯ÔÓÙ˜ ·fi ¿ÏϘ ηÙËÁÔڛ˜ ÓÔÛËÌ¿ÙˆÓ, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÓ‰ÂÈÎÙÈΤ˜ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ Ô˘ ÂÈ‚¿ÏÏÔ˘Ó ÙË ‰ÈÂÚ‡ÓËÛË Èı·Ó‹˜ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜. ∂›Û˘, ÂÎÙÈÌ¿Ù·È fiÙÈ ÛÙËÓ ·-
Paediatriki 2003;66:118-127
ÚÔ‡Û· ÌÂϤÙË, ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÈÂÚ¢ӋıËÎ·Ó Ì ÂΉËÏÒÛÂȘ Ôͤˆ˜ ¿Û¯ÔÓÙÔ˜ ·ÔÙÂÏÔ‡Ó ÌÈÎÚfi ÔÛÔÛÙfi 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›ıÂÙ·È ¿ÓÙ· ÛÙË ‰È·ÊÔÚÈ΋ ‰È·ÁÓˆÛÙÈ΋ ÛΤ„Ë ÙˆÓ ·È‰È¿ÙÚˆÓ, fiˆ˜ ·Ó·Ê¤ÚÂÙ·È Î·È ‰ÈÂıÓÒ˜ (6). ∞ӷʤÚıËΠfiÙÈ ÙÔ 9,31% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÂÍÂÙ·Ûı¤ÓÙˆÓ ·ÛıÂÓÒÓ ‹Ù·Ó ÓÂÔÁÓÈ΋˜ ËÏÈΛ·˜, Û 11 ÂÎ ÙˆÓ ÔÔ›ˆÓ Ù¤ıËÎÂ Ë ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘. ∆Ô ÔÛÔÛÙfi ·˘Ùfi ÙˆÓ ·ÛıÂÓÒÓ ·Ê›ÛÙ·Ù·È ÛËÌ·ÓÙÈο ÙˆÓ ·ÛıÂÓÒÓ 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·˙fiÌÂÓˆÓ ÁÈ· Èı·Ó‹ ÔÚÁ·ÓÈ΋ Ô͢Ԣڛ·, ÔÈ ÙÂı›Û˜ ‰È·ÁÓÒÛÂȘ Â›Ó·È ÔÛÔÛÙÈ·›· ÏÈÁfiÙÂÚ˜ ·fi ÙȘ ‰È·ÁÓÒÛÂȘ ¿ÏÏˆÓ Â˘Úˆ·˚ÎÒÓ ÂÚÁ·ÛÙËÚ›ˆÓ (17). ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ‰È·ÁÓÒÛÂȘ ÙˆÓ 85 ÂÚÈÙÒÛÂˆÓ ∫ª¡ ·ÔÙÂÏÔ‡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-ÔÍ˘Ô¿ıÂÈ·˜ ‹ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜, ‰È·ÈÛÙÒıËÎ·Ó Û 69 ·ÛıÂÓ›˜. ∏ ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ· ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ·˘Ù¤˜ ÙȘ ·Ó¿ÚÎÂȘ ÊÙ¿ÓÂÈ ÙË 1:8696 ÁÂÓÓ‹ÛÂȘ (Ì ‚¿ÛË ÙȘ 100.000 ÂÚ›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˘ ÌÂı˘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˘ 1. 2. 3. 4·. 4‚. 4Á. 5. 6. 7.
∞ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈΤ˜ ‰È·Ù·Ú·¯¤˜
ªÂı˘ÏÔÌ·ÏÔÓÈ΋ Ô͢Ԣڛ· ¢ÈηڂÔ͢ÏÈ΋ Ô͢Ԣڛ· ‚-ÔÍ›‰ˆÛ˘ ÏÈ·ÚÒÓ ÔͤˆÓ OÚÔÙÈÎfi Ô͇, Èı·Ó‹˜ ·Ó¿ÚÎÂÈ·˜ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜ °·Ï·ÎÙÈ΋ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË: Á·Ï·ÎÙÈ΋ Ô͢Ԣڛ· ∂Ó‰ÂÈÎÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ ÙˆÓ ÌÈÙÔ¯ÔÓ‰Ú›ˆÓ ¢È·Ù·Ú·¯¤˜ ÙÔ˘ ·ÎÏÔ˘ ÙˆÓ ÙÚÈηڂÔ͢ÏÈÎÒÓ ÔͤˆÓ O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ÁÏÔ˘Ù·ÚÈ΋˜ Ô͢Ԣڛ·˜ Ù‡Ô˘ π O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ Ù˘ÚÔÛÈÓ·ÈÌ›·˜ Ù‡Ô˘ ππ ∞‡ÍËÛË ˘‰ÚÔ͢-‰È·ÎÏ·‰ˆÙÈÎÒÓ ÔͤˆÓ ÂÓ‰ÂÈÎÙÈ΋ Èı·Ó‹˜ ÓfiÛÔ˘ ÔÛÌ‹˜ Ô‡ÚˆÓ Û·Ó ·fi ÛÈÚfiÈ ÛÊÂÓ‰¿ÌÔ˘ 8. 3-ÌÂı˘ÏÔ-ÁÏÔ˘Ù·ÎÔÓÈ΋ Ô͢Ԣڛ· 9. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ‰È·Ù·Ú·¯‹˜ ÙˆÓ Ó¢Úԉȷ‚È‚·ÛÙÒÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ Ù˘ ÓÙÔ·Ì›Ó˘ 10. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ Èı·Ó‹˜ ˘ÂÚÔÍ·ÏÔ˘Ú›·˜ Ù‡Ô˘ π 11. O͢Ԣڛ· ÂÓ‰ÂÈÎÙÈ΋ ‰È·Ù·Ú·¯ÒÓ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ˘ÂÚÔÍ˘ÛˆÌ¿ÙˆÓ 12·. ∞˘ÍË̤ÓË ·¤ÎÎÚÈÛË ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÌË ÂȉÈÎÔ‡ ÚÔÊ›Ï ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ 12‚. ªÂÌÔӈ̤ÓË ·‡ÍËÛË ÙÈÁÏ˘ÏÔÁÏ˘Î›Ó˘ 12Á. ªÂÌÔӈ̤ÓË ·‡ÍËÛË 3-˘‰ÚÔ͢-ÈÛÔ‚·ÏÂÚÈÎÔ‡ ÔͤԘ
15 58 10 33 41 19 3 3 5 7 2 3 6 24 10 8
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MARC-APR 03
14-05-03
14:48
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¶·È‰È·ÙÚÈ΋ 2003;66:118-127
ÙˆÓ ·Ó·ÚÎÂÈÒÓ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜. ∞˘ÍË̤ÓË 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˘¯ÓfiÙËÙ·˜ Ù˘ ·ÏηÙÔÓÔ˘Ú›·˜ Â›Ó·È ‰˘Û¯ÂÚ‹˜, ÂÍ·ÈÙ›·˜ Ù˘ ηı˘ÛÙ¤ÚËÛ˘ ÙˆÓ ÂΉËÏÒÛÂˆÓ Î·È Ù˘ ‹È·˜ ÎÏÈÓÈ΋˜ Û˘Ìو̷ÙÔÏÔÁ›·˜. ÕÏψÛÙ ÛÙË ÌÂϤÙË Ì·˜, 4/5 ·ÛıÂÓ›˜ ‹Ù·Ó ÂÓ‹ÏÈΘ. ∏ ·Ó¿ÚÎÂÈ· Ù˘ ·Ê˘‰ÚÔÁÔÓ¿Û˘ ̤Û˘ ·Ï‡ÛÔ˘ ÏÈ·ÚÒÓ ÔͤˆÓ (MCAD) ·Ó·Ê¤ÚÂÙ·È Û 7 ·ÛıÂÓ›˜, ÔÈ 3 ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ‹Ù·Ó ÙÛÈÁÁ¿ÓÈ΢ ηٷÁˆÁ‹˜. ∂›Ó·È ÁÓˆÛÙfi fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì Èı·Ó‹ ÂÓ˙˘ÌÈ΋ ·Ó¿ÚÎÂÈ· Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ (Û˘Ó‹ıˆ˜ ·ÛıÂÓ›˜ Ì ÂΉËÏÒÛÂȘ ÎÚ›ÛÂˆÓ ˘ÔÁÏ˘Î·ÈÌ›·˜, 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 ÔÚÁ·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 Â˘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 Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ·Ó·ÚÎÂÈÒÓ ·˘ÙÒÓ Ú¤ÂÈ Ó· Â›Ó·È ÛËÌ·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·ÚÒÓ ÔͤˆÓ. ∂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, ÌÂ Ô˘Û›Â˜ 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 ÙËÓ ËÏÈΛ· Î·È ÙËÓ ·ÓÙÔ¯‹ ÙÔ˘ ·ÛıÂÓÔ‡˜, ÚÈÓ ·fi ÙË Ï‹„Ë ÙˆÓ Ô‡ÚˆÓ. ∏ ‰ÔÎÈÌ·Û›· Ù˘ ·Ú·ÙÂٷ̤Ó˘ ÓËÛÙ›·˜ Û ·˘Ù‹ ÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ ÌÔÚ› Ó· ˘ÚÔ‰ÔÙ‹ÛÂÈ ÂÈΛӉ˘Ó˜ ÂΉËÏÒÛÂȘ ÁÈ· ÙË ˙ˆ‹ ÙÔ˘ ·ÛıÂÓÔ‡˜ Î·È ‰ÂÓ ·Ó·‰ÂÈÎÓ‡ÂÈ ¿ÓÙ· ÙȘ ÂÓ‰ÂÈÎÙÈΤ˜ ÌÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ÓfiÛÔ˘. ∏ ‰ÈÂÚ‡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΋˜ ÔͤˆÛ˘. ¶ÚÈÓ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙˆÓ ÂȉÈÎÒÓ ‚ÈÔ¯ËÌÈÎÒÓ Î·È ÈÛÙÔ¯ËÌÈÎÒÓ ÌÂıfi‰ˆÓ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ Ù˘ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ·˜ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ·Ï‡ÛÔ˘ ÙˆÓ ÌÈÙÔ¯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-
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Ì·Ù· ·‰ÚÒÓ ‚ÈÔ¯ËÌÈÎÒÓ ‰ÔÎÈÌ·ÛÈÒÓ (23). ¶ÚÔÛ‰ÈÔÚ›˙ÂÙ·È ÙÔ Á·Ï·ÎÙÈÎfi Î·È ˘ÚÔÛÙ·Ê˘ÏÈÎfi Ô͇ ÛÙÔ ·›Ì· Î·È ÙÔ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi Î·È Û˘ÌÏËڈ̷ÙÈο ·ÍÈÔÏÔÁÂ›Ù·È Ë Ì¤ÙÚËÛË ÙÔ˘ ‚-˘‰ÚÔ͢-‚Ô˘Ù˘ÚÈÎÔ‡ Î·È ÙÔ˘ ·ÎÂÙÔÍÈÎÔ‡ ÔͤԘ, ÛÙÔ ·›Ì· ‹ Î·È Ù· Ô‡Ú·. ™˘¯Ó¿, ÂÊ·ÚÌfi˙ÔÓÙ·È ÏÂÈÙÔ˘ÚÁÈΤ˜ ‰ÔÎÈ̷ۛ˜ Ì ÙË ¯ÔÚ‹ÁËÛË Ô˘ÛÈÒÓ fiˆ˜ Ë ÁÏ˘Îfi˙Ë (1,7 g/kg ‚¿ÚÔ˘˜) ‹ Ë ·Ï·Ó›ÓË ‹ Á‡̷ÙÔ˜ ÏÔ‡ÛÈÔ˘ Û ˘‰·Ù¿ÓıڷΘ ÚÈÓ ÙȘ ÌÂÙÚ‹ÛÂȘ ·˘ÙÒÓ ÙˆÓ Ô˘ÛÈÒÓ (24). OÈ Ù¯ÓÈΤ˜ ·˘Ù¤˜ ÂÊ·ÚÌfi˙ÔÓÙ·È Î·È Û ·ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈο ÎÏÈÓÈο ÛÙÔȯ›·, fiˆ˜ Û ÂÂÈÛfi‰È· ΢ÎÏÔÙÂÚÒÓ Â̤وÓ, Û ÎÂÊ·Ï·ÏÁ›Â˜, Û ÔÍ›· 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 ÂÚ›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 ÎÂÙÔÓÈÎÒÓ ÛˆÌ¿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·È fiÙÈ Ë ·Ó¿Ï˘ÛË ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ÙˆÓ Ô‡ÚˆÓ Û˘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 ·Ó·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¤ÙÚËÛË Ù˘ ·‡ÍËÛ˘ ÙÔ˘ ÔÚÔÙÈÎÔ‡ ÔͤԘ Î·È Ù˘ ԢڷΛÏ˘ 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˘ ÔÚÔÙÈÎÔ‡ ÔͤԘ ÛÙ· Ô‡Ú·. ªÂ ·ÚfiÌÔȘ ‰ÔÎÈ̷ۛ˜ ÂϤÁ¯ÂÙ·È Ë ·Ó¿ÚÎÂÈ· ÙÔ˘ ηٷ‚ÔÏÈÛÌÔ‡ ÙˆÓ ·ÌÈÓÔͤˆÓ. ™˘Ó‹ıˆ˜, ÌÂÙ¿ ·fi Ï‹„Ë ÚˆÙÂ˚ÓÒÓ ‹ ÂȉÈÎÒÓ ·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‰ÂÈÎÙÈο ÛÙÔȯ›· ÂÓ‰ÔÁÂÓÔ‡˜ ÌÂÈÔÓÂÎÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ (8). ∂ӉȷʤÚÔ˘Û· Â›Ó·È Ë ·Ó›¯Ó¢ÛË Ù˘ 3-ÌÂı˘ÏÔÁÏÔ˘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¿ÛÛÂÙ·È ÛÙËÓ Î·ÙËÁÔÚ›· ÙˆÓ ÔÚÈÛÙÈÎÒÓ ‰È·ÁÓÒÛˆÓ,
MARC-APR 03
14-05-03
14:48
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¶·È‰È·ÙÚÈ΋ 2003;66:118-127
‰ÈfiÙÈ ¯Ú‹˙ÂÈ ÂÚ·ÈÙ¤Úˆ ÌÂÙÚ‹ÛÂˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ Ô˘ÛÈÒÓ Î·È ‚ÈÔ¯ËÌÈ΋˜ ‰ÈÂÚ‡ÓËÛ˘. ∏ ÓfiÛÔ˜ ·˘Ù‹ ‰È·ÎÚ›ÓÂÙ·È Û ٤ÛÛÂÚȘ ÎÏÈÓÈÎÔ‡˜ ˘ÔÙ‡Ô˘˜, ÂÎ ÙˆÓ ÔÔ›ˆÓ Ë ÂÓ˙˘ÌÈ΋ Ù·˘ÙÔÔ›ËÛË Â›Ó·È ÂÊÈÎÙ‹ ÌfiÓÔÓ Û ¤Ó·Ó (6). ™˘ÓÂÎÙÈÌÒÓÙ·˜ fiÏ· Ù· ·ÓˆÙ¤Úˆ ÛÙÔȯ›· 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·ÁÓÒÛÂˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ÛÙËÓ ∂ÏÏ¿‰· (27), Û˘Ó¿ÁÂÙ·È fiÙÈ Ë ·Ó·ÊÂÚfiÌÂÓË ·ıÚÔÈÛÙÈ΋ Û˘¯ÓfiÙËÙ· ÙˆÓ ‰È·ÁÓÒÛÂˆÓ ÙˆÓ ÂÏÂÁ¯fiÌÂÓˆÓ ÓÔÛËÌ¿ÙˆÓ ˘ÔÏ›ÂÙ·È ÙÔ˘ Ú·ÁÌ·ÙÈÎÔ‡ ÌÂÁ¤ıÔ˘˜ ÙÔ˘˜ ÛÙË ¯ÒÚ· Ì·˜. ∂Ô̤ӈ˜, Ë Â˘·ÈÛıËÙÔÔ›ËÛË ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ÙˆÓ ∫ª¡ Â›Ó·È ‚·ÛÈÎfi ˙ËÙÔ‡ÌÂÓÔ Ù˘ ·È‰È·ÙÚÈ΋˜ ‰È·ÁÓˆÛÙÈ΋˜ ÛÙË ¯ÒÚ· Ì·˜. ¢ÈÂıÓÒ˜, 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¿ÙˆÓ ÂÌÂÚÈÛٷو̤Ó˘ ÎÏÈÓÈÎÔ-ÂÚÁ·ÛÙËÚȷ΋˜ ‰ÈÂÚ‡ÓËÛ˘. ∂Ê·ÚÌfi˙ÔÓÙ·È Ô‰ËÁ›Â˜ ÎÏÈÓÈ΋˜ ·ÍÈÔÏfiÁËÛ˘ Î·È ÂÈÏÔÁ‹˜ ÙˆÓ Î·Ù¿ÏÏËÏˆÓ ‰È·ÁÓˆÛÙÈÎÒÓ ÂÍÂÙ¿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‡ ·ÌÈÓÔͤˆÓ, ÔÚÁ·ÓÈÎÒÓ Î·È ÏÈ·ÚÒÓ ÔͤˆÓ Ù˘ ‚-ÔÍ›‰ˆÛ˘ ÙÔ˘ ÌÈÙÔ¯ÔÓ‰Ú›Ô˘. °È· ÙÔ ÏfiÁÔ ·˘Ùfi, ·ÍÈÔÔÈÂ›Ù·È Ë Ì¤ıÔ‰Ô˜ ÙÔ˘ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÙˆÓ ·Î˘ÏÔηÚÓÈÙÈÓÒÓ Û ‰Â›ÁÌ·Ù· ÛÙ·ÁfiÓˆÓ ·›Ì·ÙÔ˜ Ì ·Ó·Ï˘Ù‹ Ê·ÛÌ·ÙÔÁÚ·Ê›·˜ Ì·˙ÒÓ (Tandem-MS). ∏ ÂͤٷÛË Â›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˙˘ÁˆÙÒÓ Èı·ÓÔ‡ ÌÂÙ·‚ÔÏÈÎÔ‡ ÓÔÛ‹Ì·ÙÔ˜ (Û˘ÁÁÂÓ›˜ ·ÛıÂÓÒÓ, ÚÔÁÂÓÓËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜, ‰ÈÂÚ‡ÓËÛË Û ı·ÓfiÓÙ˜ SIDS). ∏ ‰È·ÊÔÚԉȷÁÓˆÛÙÈ΋ ÂÎÙ›ÌËÛË Èı·ÓÔ‡ ÓÔÛ‹Ì·ÙÔ˜ ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ ÂÓÈÛ¯‡ÂÙ·È ·fi Ù· Â˘Ú‹Ì·Ù· ‚·ÛÈÎÒÓ ‚ÈÔ¯ËÌÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ÙˆÓ ·ÛıÂÓÒÓ, Ô˘ ÂÍÂÙ¿˙ÔÓÙ·È Î·Ù¿ ÙËÓ ÚÔÛ‚ÔÏ‹ Ôͤˆ˜ ÂÂÈÛÔ‰›Ô˘. ™ÙÔÓ ÌÂÁ·Ï‡ÙÂÚÔ ·ÚÈıÌfi ÙˆÓ ·ÛıÂÓÒÓ 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›·˜ Î·È ÙˆÓ ·Ó·ÁˆÁÈÎÒÓ Ô˘ÛÈÒÓ ÛÙ· Ô‡Ú·. ∂ÈÚfiÛıÂÙ·, ‰È·Ù·Ú·¯¤˜ ÛÙÔÓ ·ÛıÂÓ‹, fiˆ˜ Ë Ï¢ÎÔÂÓ›·, Ë ıÚÔÌ‚ÔÂÓ›·, Ë ·Ó·ÈÌ›·, Ë ·‡ÍËÛË ÙÔ˘ Ô˘ÚÈÎÔ‡ ÔͤԘ, ÔÈ ‰È·Ù·Ú·¯¤˜ Ù˘ Ë·ÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ηÈ
Paediatriki 2003;66:118-127
Ù˘ ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘, ÙÔ˘ ÏÈȉ·ÈÌÈÎÔ‡ ÚÔÊ›Ï, Ë ·‡ÍËÛË Ù˘ ÎÚ·ÙÈÓÈ΋˜ ÎÈÓ¿Û˘, Ù˘ Ì˘ÛÊ·ÈÚ›Ó˘ Î·È Ù˘ ∞-ÂÌ‚Ú˘˚΋˜ ÚˆÙ½Ó˘, Ú¤ÂÈ Ó· ·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 ÔÚÁ·ÓÈ΋˜ Ô͢Ԣڛ·˜ (29). ∂Ó‰ÂÈÎÙÈ΋ ·Í›· ¤¯Ô˘Ó Î·È ‰ÔÎÈ̷ۛ˜ ·‰Ú‹˜ ·Ó›¯Ó¢Û˘ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ Ì ÎÔÈÓ‹ ¯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 ‚-ÎÂÙÔ-ÔͤˆÓ (MSUD) Î·È ÙÔ˘ ÓÈÙÚÔÚÔ˘Ûȉ›Ô˘ (brand reaction) 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 ÛÙË ‰È¢ÎÚ›ÓËÛË Ù˘ Ó¢ÚÔÏÔÁÈ΋˜ ‚Ï¿‚˘ ηÈ, Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ, ÛÙË ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘ (ÌË ÎÂÙˆÙÈ΋ ˘ÂÚÁÏ˘ÎÈÓ·ÈÌ›·, L-2-˘‰ÚÔ͢-ÁÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ·, ÁÏÔ˘Ù·ÚÈ΋ Ô͢Ԣڛ· Ù‡Ô˘ π, Û‡Ó‰ÚÔÌÔ Leigh) (30). ™Â ·ÛıÂÓ›˜ Ì ÂÓ‰ÂÈÎÙÈο ÎÏÈÓÈÎÔ-ÂÚÁ·ÛÙËÚȷο 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 ÂȉÈÎfiÙÂÚÔ 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-MS Î·È Tandem-MS. ¢È·ÁÓˆÛÙÈÎÔ› Â›Ó·È ÔÈ ÚÔÛ‰ÈÔÚÈÛÌÔ› 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·ÙÈÎfi ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÎÔ‚·Ï·Ì›Ó˘, ÙÔ˘ ¡-·ÎÂÙ˘ÏÔ·Û·ÚÙÈÎÔ‡ ÔͤԘ ÛÙË ÓfiÛÔ Canavan, Ù˘ ËÏÂÎÙÚÈÎÔ·ÎÂÙfiÓ˘ (succinylace-tone) ÛÙËÓ Ù˘ÚÔÛ˘Ó·ÈÌ›· Ù‡Ô˘ (π), ÙÔ˘ 4-˘‰ÚÔ͢-‚Ô˘Ù˘ÚÈ· ÔͤԘ, ÙÔ˘ Ì‚·ÏÔÓÈÎÔ‡ ÔͤԘ, ÙˆÓ L- Î·È D-ÈÛÔÌÂÚÒÓ ÙÔ˘ 2˘‰ÚÔ͢-ÁÏÔ˘Ù·ÚÈÎÔ‡ ÔͤԘ ÛÙȘ ·ÓÙ›ÛÙÔȯ˜ ÔÍ˘Ô˘Ú›Â˜. ∂›Û˘, ÔÛÔÙÈο ÚÔÛ‰ÈÔÚ›˙ÂÙ·È ÙÔ ÔÚÔÙÈÎfi Ô͇ ÛÙȘ ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·ÎÏÔ˘ Ù˘ Ô˘Ú›·˜, › ˘Ô„›·˜ ÌÂÚÈ΋˜ ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜. ∏ ‰ÈÂÚ‡ÓËÛË Ù˘ ·‡ÍËÛ˘ ÂȉÈÎÒÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, › ˘Ô„›·˜ ÌÂÈÔÓÂÎÙÈÎÔ‡ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÂȉÈÎÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ ·ÓÙȉڿÛˆÓ, ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÂȉÈÎÒÓ Ù¯ÓÈÎÒÓ ·Ó¿Ï˘Û˘ GC-MS, fiˆ˜ ÛÙȘ ÓfiÛÔ˘˜: Û‡Ó‰ÚÔÌÔ Smith-Lemli-Opitz (·‡ÍËÛË 7b-cholestanol), ÙÚÈÌÂı˘Ï·ÌÈÓÔ˘Ú›· (trymethylaminuria) ÛÂ
125
MARC-APR 03
14-05-03
14:48
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¶·È‰È·ÙÚÈ΋ 2003;66:118-127
·Ó¿ÚÎÂÈ· Ù˘ Ë·ÙÈ΋˜ Û˘ÓıÂÙ¿Û˘ (trimethyamine N-oxide), ‰ÈÌÂı˘ÏÔÁÏ˘ÎÈÓÔ˘Ú›· (dimethylglycinuria) Û ·Ó¿ÚÎÂÈ· Ù˘ ·Ê˘‰ÚÔÁÔÓ¿Û˘ (dimethylglycine dehydrogenase), ÌÂÈÔÓÂÎÙÈÎfi˜ ÌÂÙ·‚ÔÏÈÛÌfi˜ ÙˆÓ ¯ÔÏÈÎÒÓ ÔͤˆÓ Ì ·‡ÍËÛË ÂӉȿÌÂÛˆÓ 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¿ÚÎÂÈ· ÙˆÓ ÂÓ˙‡ÌˆÓ ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ Ó¢Úԉȷ‚È‚·ÛÙÒÓ ÂϤÁ¯ÂÙ·È Ì ÙÔÓ ÔÛÔÙÈÎfi ÚÔÛ‰ÈÔÚÈÛÌfi ÙÔ˘˜ ÛÙÔ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi Ô˘ÛÈÒÓ, fiˆ˜ Â›Ó·È ÙÔ Á-·ÌÈÓÔ‚Ô˘Ù˘ÚÈÎfi Ô͇ (GABA), ÙÔ ÔÌÔ‚·Ï˘ÓÈÎfi Ô͇ (HVA), Ë ÓÙÔ·Ì›ÓË, ÙÔ 5-˘‰ÚÔ͢-ÈÓ‰ÔÏÔÔÍÈÎfi Ô͇ Î·È ÔÈ ÙÂÚ›Ó˜. ™¯ÂÙÈο, ··ÈÙÔ‡ÓÙ·È ÂȉÈΤ˜ 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 ÂȉÈ΋ 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·ÏÔÓÈ΋˜ Ô͢Ԣڛ·˜ Î·È ÔÌÔ΢ÛÙ˘ÓÔ˘Ú›·˜ (¶›Ó·Î·˜ 2, ·ÛıÂÓ‹˜ 5‚). ∏ ·Ó¿ÚÎÂÈ· Û˘ÌÌÂÙÔ¯‹˜ Ù˘ ˘ÚȉÔ͛Ӣ 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¿ÛË Ù˘ ‚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 ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, Ù· ÔÔ›· Û˘Ó‹ıˆ˜ Â›Ó·È ·ıÔÏÔÁÈο ÙËÓ ÂÚ›Ô‰Ô ÙˆÓ ÂÂÈÛÔ‰›ˆÓ Ù˘ ÓfiÛÔ˘. ¶·Ú’ fiÙÈ Ë Û˘¯ÓfiÙËÙ· Ù˘ ·Ó¿ÚÎÂÈ·˜ ·˘Ù‹˜ ÛÙËÓ ∂˘ÚÒË ‰ÂÓ Â›Ó·È Ôχ Û¿ÓÈ· (1:60-100 ¯ÈÏÈ¿‰Â˜ ÁÂÓÓ‹ÛÂȘ), ·fi ÙȘ ·ÓˆÙ¤Úˆ ·Ó·Ï‡ÛÂȘ ‰ÂÓ ‰È·ÈÛÙÒıËΠÂÓ‰ÂÈÎÙÈ΋ Ô͢Ԣڛ·. ∞ӷχÛÂȘ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ ·fi 42 ·ÛıÂÓ›˜ (¶›Ó·Î·˜ 3, ¡Ô 12) ·ÚÔ˘Û›·Û·Ó ·‡ÍËÛË Û ÔÚÈṲ̂ӷ ÂÍ ·˘ÙÒÓ, Ô˘ ‰ÂÓ ÙÂÎÌËÚÈÒÓÔ˘Ó ÂȉÈ΋ ÂÈÎfiÓ· ÂÓ‰ÔÁÂÓÔ‡˜ ÂÓ˙˘ÌÈ΋˜ ·Ó¿ÚÎÂÈ·˜. ™˘¯Ó¿, ÂÓ‰ÔÁÂÓ‹ ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù· ›Ù ÌÂÌÔӈ̤Ó˜ ÔÚÁ·ÓÈΤ˜ ‚Ï¿‚˜, fiˆ˜ ÙÔ˘ ‹·ÙÔ˜, ÙˆÓ ÓÂÊÚÒÓ, ÙÔ˘ ÂÓÙ¤ÚÔ˘ ‹ Ë Ï‹„Ë Ê·ÚÌ¿ÎˆÓ Î·È ÂȉÈ΋˜ ‰È·ÙÚÔÊ‹˜, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ‰È·Ù·Ú·¯¤˜ ÙˆÓ ÔÚÁ·ÓÈÎÒÓ ÔͤˆÓ, Ë ·ÍÈÔÏfiÁËÛË ÙˆÓ ÔÔ›ˆÓ Â›Ó·È ·ÌÊ›‚ÔÏË (8,12). ¶ÔÏÏ¿ ·Ú·ÂÌÙÈο Ô˘ Û˘ÓÔ‰Â‡Ô˘Ó Ù· ‰Â›ÁÌ·Ù· ·ÛıÂÓÒÓ, ·Ó·Ê¤ÚÔ˘Ó ÙËÓ ÎÏÈÓÈ΋ ÙÔ˘˜ ηٿÛÙ·ÛË Ì ÁÂÓÈÎÔ‡˜ fiÚÔ˘˜, fiˆ˜ ·Ó·Ù˘Íȷ΋ Î·È „˘¯ÔÎÈÓËÙÈ΋ ηı˘ÛÙ¤ÚËÛË, ·Ó·Ù˘ÍȷΤ˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘, ÂÁÎÂÊ·ÏÈ΋ ·Ú¿Ï˘ÛË Î·È Ô-
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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‹ÏˆÛË 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¿ ÂÚÈÛÛfiÙÂÚˆÓ ÛÙÔȯ›ˆÓ ÙˆÓ ·ÛıÂÓÒÓ. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ù· ·ÓˆÙ¤Úˆ ·Ó·‰ÂÈÎÓ‡Ô˘Ó ÂÓ Ì¤ÚÂÈ 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·˜ ·˘ÙÒÓ ÙˆÓ 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›˜, ÌÔÚÔ‡Ó Ó· ÂÈÙ¢¯ıÔ‡Ó Ì ÙËÓ ÂÚ·ÈÙ¤Úˆ ·Ó¿Ù˘ÍË ÙˆÓ 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· ÓÔÛÔÎÔÌ›· Ù˘ ¯ÒÚ·˜, ÔÈ ÔÔ›ÔÈ ÛÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô 1996-2001 Ì¿˜ ·¤ÛÙÂÈÏ·Ó ‰Â›ÁÌ·Ù· ÙˆÓ ·ÛıÂÓÒÓ Ì·˙› Ì ÂÓËÌÂÚˆÙÈο ÛËÌÂÈÒÌ·Ù·. ∂›Û˘, ¢¯·ÚÈÛÙԇ̠ÙËÓ Î·. ∂. ªÈ¯ÂϷοÎË, ηıÒ˜ Î·È ÙÔ ˘fiÏÔÈÔ ÂÈÛÙËÌÔÓÈÎfi ÚÔÛˆÈÎfi ÙÔ˘ πÓÛÙÈÙÔ‡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. ¡ew York: 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 Italian pediatric population: a national retrospective survey. J Pediatr 2002;140:321-327. 4. Green A, Pollitt RJ. Population newborn screening for inherited metabolic disease: current UK perspectives. J Inherit Metab Dis 1999;22:572-579. 5. Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics 2000;105:e10. 6. Scriver CR, Beaudet AL, Sly WS, Valle. The metabolic and molecular bases of inherited disease. In: Genetics, biochemistry and molecular bases of variant human phenotypes. 8th ed. ¡ew York: McGraw-Hill; V1,1,345.V1,66, p. 1327-1396. V2,93; 2001. p. 2125-2140. 7. Tom Strachan, Read AP. Molecular pathology. Human molecular genetics. 2nd ed. U.K.: Bios; 1999. p. 377-422. 8. Hoffman GF, Nyhan WL, Zschoche J, Kahler SG, Mayatepek E. Organic acid analysis: approach to the diagnosis of organic acidurias. In: Inherited metabolic diseases. Baltimore: Lippincott Williams & Wilkins; 2002. p. 319-328. 9. Lehnert W. Long-term results of selective screening for inborn errors of metabolism. Eur J Pediatr 1994;153(7 Suppl 1):S9-13.
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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. 8961130. 11. Sweetman L. Organic acid analysis. Techniques in diagnostic human biochemical genetics. A laboratory manual. 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 biochemical laboratories: a laboratory manual. 1st ed. New York: WileyLiss; 1991. p. 5-120. 14. Vreken P, van Lint AE, Bootsma AH, Overmars H, Wanders RJ, van Gennip AH. Rapid diagnosis of organic acidemias and fatty-acid oxidation defects by quantitative electrospray tandem-MS acyl-carnitine analysis in plasma. Adv Exp Med Biol 1999;466:327-337. 15. Tanaka K, Hine DG. Compilation of gas chromatographic retention indices of 163 metabolically important organic acids, and their use in detection of patients with organic acidurias. 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 of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal results. Clin Chem 1997;43:2106-2113. 17. Hoffmann GF. Selective screening for inborn errors of metabolism - past, present and future. Eur J Pediatr 1994;153 (Suppl 1):S2-8. 18. Lyon G, Adams RD, Konodny EH. Neurology of hereditary metabolic diseases of children. Laboratory tests for the diagnosis of hereditary metabolic encephalopathies. 2nd ed. New York: McGraw-Hill; 1996. p. 340-350, 6-41. 19. Gibson KM, Hoffmann GF, Hodson AK, Bottiglieri T, Jakobs C. 4-Hyrdoxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism. Neuropediatrics 1998;29:14-22. 20. Wanders RJ, Vreken P, den Boer ME, Wijburg FA, van Gennip AH, Ijlst L. Disorders of mitochondrial fatty acyl-CoA B-oxidation. J Inherit Metab Dis 1999;22:442-487.
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HÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 22-10-2002 HÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 10-01-2003 ¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: °ÂÒÚÁÈÔ˜ ¢. ª·ÚfiÔ˘ÏÔ˜ µÈÔ·ıÔÏfiÁÔ˜, ∂ÈÌÂÏËÙ‹˜ ∞’ ª·Î‰ÔÓ›·˜ 56, ¡. ∏Ú¿ÎÏÂÈÔ, ∞ÙÙÈ΋
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ORIGINAL ARTICLE
∞ÍÈÔÏfiÁËÛË Ù˘ Û˘ÌÌfiÚʈÛ˘ ÛÙË ıÂڷ›· ·ÔÛȉ‹ÚˆÛ˘ Û ·È‰È¿ Ô˘ ¿Û¯Ô˘Ó ·fi ÔÌfi˙˘ÁË ‚-ÌÂÛÔÁÂȷ΋ ·Ó·ÈÌ›· ∫. ¶··‰ÔÔ‡ÏÔ˘ - §ÂÁ̤ÏÔ˘1, ª. ∞ı·Ó·Û›Ô˘ - ªÂÙ·Í¿2, °. µ·ÚÏ¿Ì˘3, ™. ∫·Ú·Ì¤Ú˘3
Evaluation of compliance with chelation therapy in children with beta-thalassaemia major K. Papadopoulou - Legbelou1, M. Athanasiou - Metaxa2, G. Varlamis3, S. Karamperis3
¶ÂÚ›ÏË„Ë: ∆Ô Ù·ÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘ 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 Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘-·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ Î·È Ë Û˘Û¯¤ÙÈÛ‹ Ù˘ Ì ‰È¿ÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ Ë ËÏÈΛ·, ÙÔ Ê‡ÏÔ, Ë ¯ÚÔÓÈ΋ ‰È¿ÚÎÂÈ· Ù˘ ·ÔÛȉ‹ÚˆÛ˘, ÙÔ Û‡ÓÔÏÔ ÙˆÓ ÌÂÙ·ÁÁ›ÛˆÓ, Ë ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ÙË ÌÂÙ¿ÁÁÈÛË Î·È Ë ÊÂÚÚÈÙ›ÓË ÙÔ˘ ÔÚÔ‡. ªÂÏÂÙ‹ıËÎ·Ó 90 ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ (48 ·ÁfiÚÈ· Î·È 42 ÎÔÚ›ÙÛÈ·) ËÏÈΛ·˜ 3-18 ¯ÚfiÓˆÓ (̤ÛË ËÏÈΛ·: 12,3±4,4 ¤ÙË), ÔÈ ÔÔ›ÔÈ ‚Ú›ÛÎÔÓÙ·Ó Û ٷÎÙÈÎfi ÚfiÁÚ·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 3 ÔÌ¿‰Â˜ ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· (ÔÌ¿‰· ∞: <10 ÂÙÒÓ, ÔÌ¿‰· µ: 10-15 ÂÙÒÓ, ÔÌ¿‰· °: >15 ÂÙÒÓ) Î·È Û 3 ÔÌ¿‰Â˜ ·Ó¿ÏÔÁ· Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (1Ë ÔÌ¿‰·: η΋, 2Ë ÔÌ¿‰·: ̤ÙÚÈ·, 3Ë ÔÌ¿‰·: ηϋ). ¢È·ÈÛÙÒıËΠη΋ Û˘ÌÌfiÚʈÛË Û 11 ·ÛıÂÓ›˜ (12%), ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË Û 20 (22%) Î·È Î·Ï‹ Û˘ÌÌfiÚʈÛË Û 59 ·ÛıÂÓ›˜ (66%). ∏ ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË ·Ú·ÙËÚ‹ıËΠ̠ÙËÓ ·‡ÍËÛË Ù˘ ËÏÈΛ·˜, ÙˆÓ ¯ÚfiÓˆÓ ·ÔÛȉ‹ÚˆÛ˘ Î·È ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÌÂÙ·ÁÁ›ÛˆÓ, ÂÓÒ ·fi ÙÔ Ê‡ÏÔ Ê¿ÓËΠfiÙÈ Ù· ·ÁfiÚÈ· ›¯·Ó ¯ÂÈÚfiÙÂÚË Û˘ÌÌfiÚʈÛË Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ·. ∂›Û˘, Ë Î·Î‹ Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË Ê¿ÓËΠfiÙÈ Û¯ÂÙ›˙ÂÙ·È Ì ˘„ËϤ˜ ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘ ÙÔ˘ ÔÚÔ‡.
Abstract: Regular transfusion and chelation therapy in ‚-thalassaemia have improved survival, particularly when associated with optimal compliance. The aim of this study was to investigate compliance with chelation therapy of patients with ‚-thalassaemia major who were treated with regular transfusions and chelation therapy, and the relationships between compliance and age, sex, duration of chelation therapy, number of blood transfusions and post-transfusional haemoglobin and serum ferritin levels. Ninety patients, 48 boys and 42 girls, aged 3-18 years (mean age: 12.3±4.4 years) were studied. They were all receiving regular transfusions and started chelation therapy with desferrioxamine at serum ferritin levels of approximately 1000 ng/ml. The patients were divided into three groups according to age (group A: <10 years, group B: 10-15 years, group C: >15 years). They were also classified into three groups according to compliance with chelation therapy (group I: poor, group II: moderate, group III: optimal compliance). Eleven patients (12%) exhibited poor compliance, 20 (22%) moderate and 59 (66%) optimal compliance. The poorest compliance with chelation therapy was observed in older patients with a higher number of blood transfusions and boys showed worse compliance than girls. The non-compliant patients had a higher mean serum ferritin level. In this study the majority of patients showed good compliance with chelation therapy. The age at commencement of desferrioxamine treatment 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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¶·È‰È·ÙÚÈ΋ 2003;66:128-132
Paediatriki 2003;66:128-132
∞fi ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Û˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘ Î·È ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ¤¯Ô˘Ó ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ηϋ Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË. ∏ ¤ÁηÈÚË ¤Ó·ÚÍË Ù˘ ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ÚÒÙË ·È‰È΋ 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.
of compliance. The authors believe that early introduction of chelation will not only have a direct effect on iron overload, but will also lead to continued good compliance.
§¤ÍÂȘ ÎÏÂȉȿ: ÔÌfi˙˘ÁË ‚-ª∞, ·ÔÛȉ‹ÚˆÛË, Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË.
Key words: beta-thalassaemia major, chelation therapy, compliance.
∂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 ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·ÈÌÔÛȉ‹ÚˆÛ˘ (1). ∆Ô Ù·ÎÙÈÎfi ÚfiÁÚ·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΋˜ ·ÔÛȉ‹ÚˆÛ˘ ¤¯ÂÈ ·˘Í‹ÛÂÈ ÛËÌ·ÓÙÈο ÙÔÓ Ì¤ÛÔ fiÚÔ ÂÈ‚›ˆÛ˘ ÙˆÓ ·Û¯fiÓÙˆÓ. ¶·Ú’ fiÏ· ·˘Ù¿, ÔÈ ÂÈÏÔΤ˜ ·fi Ù· ‰È¿ÊÔÚ· fiÚÁ·Ó·, Ô˘ ÔÊ›ÏÔÓÙ·È ÛÙËÓ ·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˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË Û ¿Û¯ÔÓÙ˜ ·fi ‚ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘-·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ Î·È Ë Û˘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¿ÁÁÈÛË Î·È Ë ÊÂÚÚÈÙ›ÓË ÙÔ˘ ÔÚÔ‡.
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¯ÔÓÙ˜ ¯ˆÚ›ÛÙËηÓ, ›Û˘, Û ÙÚÂȘ ÔÌ¿‰Â˜: Ë 1Ë ÔÌ¿‰· ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì η΋ Û˘ÌÌfiÚʈÛË (·ÔÛȉ‹ÚˆÛË <4 ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·), Ë 2Ë ÔÌ¿‰· ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ Ì ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË (·ÔÛȉ‹ÚˆÛË 4-5 ÊÔÚ¤˜ ÙËÓ Â‚‰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¿ÊËÎÂ Ô Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·ÁÁ›ÛÂˆÓ (ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜), Ô Ì¤ÛÔ˜ fiÚÔ˜ ÙˆÓ ÙÈÌÒÓ ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ 5 ¯ÚfiÓˆÓ Ù˘ ·ÈÌÔÛÊ·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·ÛÈÒÓ Ì ÙË ¯Ú‹ÛË ÙˆÓ ·Î¤ÙˆÓ SPSS for Windows ’95 Î·È StatCalc ÙÔ˘ Epilnfo 2000. ∏ ‰È·‰Èηۛ· Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ·Ó¿Ï˘Û˘ ÂÚÈÂÏ¿Ì‚·Ó ˘ÔÏÔÁÈÛÌfi ÁÈ· οı ÌÂÙ·‚ÏËÙ‹ Ù˘ ̤Û˘ ÙÈÌ‹˜ (n) Î·È Ù˘ 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 ÔÈ Û˘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 ÌÂÙ·‚ÏËÙÒÓ Ì ÙË ÊÂÚÚÈÙ›ÓË, ÂÊ·ÚÌfiÛÙËÎ·Ó ÌÔÓ٤Ϸ ÔÏÏ·Ï‹˜ Û˘Û¯¤ÙÈÛ˘ (4).
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 ËÏÈΛ·: 12,3±4,4 ¤ÙË). OÈ ·ÛıÂÓ›˜ ‚Ú›ÛÎÔÓÙ·Ó Û ٷÎÙÈÎfi ÚfiÁÚ·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· Ì ÙËÓ ËÏÈΛ·: Ë ÔÌ¿‰· ∞ (¡=27 ·ÛıÂÓ›˜) ÂÚÈÂÏ¿Ì‚·Ó ·ÛıÂÓ›˜ ËÏÈΛ·˜ 3-10 ¯ÚfiÓˆÓ, Ë ÔÌ¿‰· µ (¡=26 ·ÛıÂÓ›˜) ËÏÈΛ·˜
∞ÔÙÂϤÛÌ·Ù· O ̤ÛÔ˜ fiÚÔ˜ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂÙ¿ÁÁÈÛË, Ô Ì¤ÛÔ˜ fiÚÔ˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÙÔ˘ ÔÚÔ‡, Ô Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜ Î·È Ë ¯ÚÔÓÈ΋ ‰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 ·ÔÛȉ‹ÚˆÛË, ‰È·ÈÛÙÒıËÎ·Ó Ù· ÂÍ‹˜: η΋ Û˘ÌÌfiÚʈÛË Â›¯·Ó 11 ·ÛıÂÓ›˜ (2 ·fi ÙËÓ ÔÌ¿‰· ∞, 2 ·fi ÙËÓ ÔÌ¿‰· µ Î·È 7 ·fi ÙËÓ ÔÌ¿‰· °), ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË Â›¯·Ó 20 ·ÛıÂÓ›˜ (3 ·fi ÙËÓ ÔÌ¿‰· ∞, 6 ·fi
129
MARC-APR 03
14-05-03
14:48
™ÂÏ›‰·130
¶·È‰È·ÙÚÈ΋ 2003;66:128-132
Paediatriki 2003;66:128-132
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˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË, ‰È·ÈÛÙÒıËΠfiÙÈ ˘¿Ú¯ÂÈ Û˘Û¯¤ÙÈÛË Ù˘ ÙÈÌ‹˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÌfiÓÔ Ì ÙËÓ ·ÔÛȉ‹ÚˆÛË Î·È Ë ‰È·ÊÔÚ¿ Â›Ó·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ (p<0,001).
ÙËÓ ÔÌ¿‰· µ Î·È 11 ·fi ÙËÓ ÔÌ¿‰· °) Î·È Î·Ï‹ Û˘ÌÌfiÚʈÛË Â›¯·Ó 59 ·ÛıÂÓ›˜ (22 ·fi ÙËÓ ÔÌ¿‰· ∞, 18 ·fi ÙËÓ ÔÌ¿‰· µ Î·È 19 ·fi ÙËÓ ÔÌ¿‰· °) (¶›Ó·Î·˜ 2). ∞fi ÙȘ Û˘Û¯ÂÙ›ÛÂȘ ÙˆÓ ‰È·ÊfiÚˆÓ ·Ú·Ì¤ÙÚˆÓ ˆ˜ ÚÔ˜ ÙË Û˘ÌÌfiÚʈÛË, ÚԤ΢„ fiÙÈ Ë Û˘ÌÌfiÚʈÛË 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·ÁÁ›ÛÂˆÓ (ÌÔÓ¿‰Â˜ ·›Ì·ÙÔ˜) (p<0,05) (¶›Ó·Î˜ 2 Î·È 3, ∂ÈÎfiÓ· 1). ŸÛÔÓ ·ÊÔÚ¿ ÛÙË ÊÂÚÚÈÙ›ÓË, Ê·›ÓÂÙ·È fiÙÈ ÔÈ ¿Û¯ÔÓÙ˜ Ô˘ ›¯·Ó η΋ Î·È Ì¤ÙÚÈ· Û˘ÌÌfiÚʈÛË Â›¯·Ó ÈÔ ˘„ËϤ˜ ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘ (ÂÚ›Ô˘ ›‰È˜ ÙÈ̤˜ ÛÙȘ ‰‡Ô ÚÒÙ˜ ÔÌ¿‰Â˜), ÂÓÒ fiÛÔÈ Â›¯·Ó ηϋ Û˘ÌÌfiÚʈÛË Â›¯·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈο ¯·ÌËÏfiÙÂÚ˜ ÙÈ̤˜ (p<0,01) (¶›Ó·Î·˜ 3 Î·È ∂ÈÎfiÓ· 2). ∏ ̤ÛË ÙÈÌ‹ Ù˘ ·ÈÌÔÛÊ·ÈÚ›Ó˘ ÚÈÓ ·fi ÙË ÌÂÙ¿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¿ ÔÈ ‰È·ÊÔÚ¤˜ 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-
™˘˙‹ÙËÛË OÈ Ù·ÎÙÈΤ˜ ÌÂÙ·ÁÁ›ÛÂȘ ÛÙËÓ ÔÌfi˙˘ÁË ‚-ª∞ ηٷÛÙ¤ÏÏÔ˘Ó ÙËÓ ÂÍˆÌ˘ÂÏÈ΋ ÂÚ˘ıÚÔÔ›ËÛË Î·È ÚÔÊ˘Ï¿ÛÛÔ˘Ó ·fi ÙËÓ ÂÌÊ¿ÓÈÛË ÛÔ‚·Ú‹˜ ·Ó·ÈÌ›·˜ (5). ŸÌˆ˜, Ë ·˘ÍË̤ÓË ÚfiÛÏË„Ë Ûȉ‹ÚÔ˘ ·fi ÙȘ Ù·ÎÙÈΤ˜ ÌÂÙ·ÁÁ›ÛÂȘ ‰È·Ù·Ú¿ÛÛÂÈ ÙÔÓ ÌÂÙ·‚ÔÏÈÛÌfi ÙÔ˘ Î·È Ô‰ËÁ› Û ÏÂfiÓ·ÛÌ· Ûȉ‹ÚÔ˘, ÙÔ ÔÔ›Ô ÂÓ·ÔÙ›ıÂÙ·È Û fiÏÔ˘˜ ÙÔ˘˜ ÈÛÙÔ‡˜ Î·È Ô‰ËÁ› Û ÚÔ˚Ô‡Û· ›ÓˆÛË Î·È ÏÂÈÙÔ˘ÚÁÈ΋ ·Ó¿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˘ Î·È Ì›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¯fiÓÙˆÓ ·fi ‚-ª∞, ·Ó¿ ÔÌ¿‰· ËÏÈΛ·˜ OÌ¿‰· ∞ ∞ µ °
º‡ÏÔ ∫
14 14 20
∏b ª¤ÛË ÙÈÌ‹ (g/dl)
ºÂÚÚÈÙ›ÓË ª¤ÛË ÙÈÌ‹ (ng/ml)
MÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ (n)
∞ÔÛȉ‹ÚˆÛË (Ì‹Ó˜)
9,467 9,678 9,763
1494,07 2115 2378,97
18-200 85-440 105-518
3-90 30-138 60-192
13 12 17
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 ·ÔÛȉ‹ÚˆÛË ™˘ÌÌfiÚʈÛË ∫·Î‹ ª¤ÙÚÈ· ∫·Ï‹
∞ÚÈıÌfi˜ ·Û¯fiÓÙˆÓ ∞Á. ∫. ™‡ÓÔÏÔ
∞
OÌ¿‰Â˜ µ
°
7 9 32
2 3 22
2 6 18
7 11 19
4 11 27
11 20 59
∏ÏÈΛ· (¯ÚfiÓÈ·) ª¤ÛË ÙÈÌ‹ ∆˘È΋ ·fiÎÏÈÛË 14,55 13,68 11,13
3,57 3,48 4,62
p <0,05 <0,05 <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
∞ÔÛȉ‹ÚˆÛË (Ì‹Ó˜) ªÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ ºÂÚÚÈÙ›ÓË (ng/ml)
130
∫·Î‹
™˘ÌÌfiÚʈÛË ª¤ÙÚÈ·
∫·Ï‹
p
134,16±47,04 349±130,61 2409,9±1132,35
124,8±36,24 304±106,65 2488,5±823,84
89,64±57,72 230,62±154,63 1792,2±765,99
<0,01 <0,05 <0,01
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HÏÈΛ· (Ì‹Ó˜) ÃÚÔÓÈ΋ ‰È¿ÚÎÂÈ· ·ÔÛȉ‹ÚˆÛ˘ (Ì‹Ó˜) ªÔÓ¿‰Â˜ ·›Ì·ÙÔ˜ ∂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˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (η΋, ̤ÙÚÈ·, ηϋ).
Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ·ÛıÂÓ›˜ Ô˘ ¿Ú¯ÈÛ·Ó ·ÔÛȉ‹ÚˆÛË ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘ (12,13). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, fiÏÔÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘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 ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Â›¯Â ηϋ ¤ˆ˜ ̤ÙÚÈ· Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (88%). ™Â ‰‡Ô ÌÂϤÙ˜ Ô˘ ¤ÁÈÓ·Ó Û ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¿Ú¯ÈÛ·Ó ·ÔÛȉ‹ÚˆÛË ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ‰È·ÈÛÙÒıËΠfiÙÈ ÙÔ ÔÛÔÛÙfi Ù˘ Û˘ÌÌfiÚʈÛ˘ ‹Ù·Ó <70%, ÂÓÒ ÔÈ ·ÛıÂÓ›˜ Ô˘ Û˘ÌÌÔÚÊÒıËÎ·Ó Û ÌÈÎÚfiÙÂÚÔ ÔÛÔÛÙfi ‹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‡ÌÂÓˆÓ ÌÔÓ¿‰ˆÓ ·›Ì·ÙÔ˜. ∞fi ÙË ÌÂϤÙË ÙˆÓ ËÏÈÎÈÒÓ Ê¿ÓËΠfiÙÈ ÚfiÎÂÈÙ·È ÁÈ· ·È‰È¿ Ù˘ ÂÊË‚È΋˜ ËÏÈΛ·˜, 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· ÌÂÏÂÙÒÓ Ô˘ ÚԷӷʤÚıËÎ·Ó (2,8). ™Â Ì›· ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË ÙˆÓ Richardson Î·È Û˘Ó (14), ‚Ú¤ıËΠ›Û˘ fiÙÈ Ë Û˘ÌÌfiÚʈÛË Â›Ó·È ·ÓÙÈÛÙÚfiʈ˜ ·Ó¿ÏÔÁË Ì ÙËÓ 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·
∫·Î‹
ª¤ÙÚÈ·
∫·Ï‹
ºÂÚÚÈÙ›ÓË (ng/ml) ∂ÈÎfiÓ· 2. ª¤Û˜ ÙÈ̤˜ Ù˘ ÊÂÚÚÈÙ›Ó˘ Û ۯ¤ÛË Ì ÙË Û˘ÌÌfiÚʈÛË ÛÙËÓ ·ÔÛȉ‹ÚˆÛË (η΋, ̤ÙÚÈ·, ηϋ).
ÂÊË‚È΋˜ ËÏÈΛ·˜, Ù· ÔÔ›· Èı·ÓfiÓ ÏfiÁˆ ÔÚÌÔÓÈÎÒÓ ÌÂÙ·‚ÔÏÒÓ Á›ÓÔÓÙ·È ÈÔ ·ÚÔÚÌËÙÈο Î·È ·ÓÙȉڷÛÙÈο ·fi Ù· ÎÔÚ›ÙÛÈ·. ¢È·ÈÛÙÒıËÎÂ, ›Û˘, fiÙÈ Ë ÔÌ¿‰· ·ÛıÂÓÒÓ Ì ηχÙÂÚË Û˘ÌÌfiÚʈÛË ·ÚÔ˘ÛÈ¿˙ÂÈ ¯·ÌËÏfiÙÂÚ˜ ÙÈ̤˜ ÊÂÚÚÈÙ›Ó˘. ∆· Â˘Ú‹Ì·Ù· Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Û˘ÌʈÓÔ‡Ó, ›Û˘, Ì ÙË ÌÂϤÙË ÙˆÓ Maurer Î·È Û˘Ó (8), ηıÒ˜ ›Û˘ Î·È Ì ÙË ÌÂϤÙË ÙˆÓ ∫·ÙÙ¿ÌË Î·È Û˘Ó (15), ÛÙËÓ ÔÔ›· ‰È·ÈÛÙÒıËΠÙËÓ ÙÂÏÂ˘Ù·›· 15ÂÙ›· Ì›ˆÛË ÙˆÓ ÙÈÌÒÓ Ù˘ ÊÂÚÚÈÙ›Ó˘ ÙˆÓ ·Û¯fiÓÙˆÓ ·fi ‚-ª∞ Î·È ‚ÂÏÙ›ˆÛË Ù˘ Û˘ÌÌfiÚʈÛ˘ ÛÙËÓ ·ÔÛȉ‹ÚˆÛË. ™˘ÌÂÚ·ÛÌ·ÙÈο, ·fi ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ÚÔ·ÙÂÈ fiÙÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi ÔÌfi˙˘ÁË ‚-ª∞ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ٷÎÙÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ¿ÁÁÈÛ˘ Î·È ·ÔÛȉ‹ÚˆÛ˘ ·fi ÙËÓ ·Ú¯‹ Ù˘ ÓfiÛÔ˘, ¤¯Ô˘Ó ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi Û¯ÂÙÈο ηϋ Û˘ÌÌfiÚʈÛË ÛÙË ıÂڷ›· ·ÔÛȉ‹ÚˆÛ˘. ∂ÎÙfi˜ fï˜ ·fi ÙË Û˘ÌÌfiÚʈÛË, ÛËÌ·ÓÙÈÎfi ÚfiÏÔ 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 ˘ÂÚÊfiÚÙˆÛË ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ Ì ۛ‰ËÚÔ, ·ÏÏ¿ Û˘Ó¿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 Hematol 1995;32:288-296. 2. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997;89:739-761. 3. µuja LM, Roberts WC. Iron in the heart. Etiology and clinical significance. Am J Med 1971;51:209-221. 4. Armitage P, Berry G. Statistical methods in medical research. 2nd ed. Oxford: Blackwell Scientific Publications; 1989. 5. Fosburg MT, Nathan DG. Treatment of Cooley’s anemia. Blood 1990;76:435-444.
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6. Giardina PJ, Grady RW. Chelation therapy in betathalassemia: the benefits and limitations of desferrioxamine. Semin Hematol 1995;32:304-312. 7. Weatherall DJ, Clegg JB. The thalassaemic syndromes. 3rd ed. Oxford: Blackwell Scientific Publications; 1981. 8. Maurer HS, Lloyd-Still JD, Ingrisano C, Gonzalez-Crussi F, Honig GR. A prospective evaluation of iron chelation therapy in children with severe beta-thalassemia. A six-year study. 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. A decade 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 with homozygous beta-thalassemia. N Engl J Med 1994;331:574-578. 11. Cohen A, Martin M, Schwartz E. Response to long-term deferoxamine therapy in thalassemia. J Pediatr 1981;99:689-694. 12. Borgna-Pignatti C, Piga A, Rugolotto S, De Stefano P, Di Palma AM, Gamberini R et al. Survival and disease complications in thalassemia major. Bone Marrow Transplant 1997;19 (Suppl 2):S16-S17. 13. Ladis V, Papadopoulou A, Athanassaki C, Palamidou F,
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Kostaridou S, Berdousi E et al. Long term survival and causes of death in patients with thalassemia under conventional 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 by subcutaneous desferrioxamine in patients with thalassaemia 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 among transfused patients with thalassemia on desferrioxamine in a period of 15 years. Proceedings of the 7th International Conference 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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∂¡¢π∞º∂ƒOÀ™∞ ¶∂ƒπ¶∆ø™∏
Paediatriki 2003;66:140-144
CASE REPORT
™‡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 report J. J. Ignatiadis, M. Z. Goudesidou, A. L. Papadopoulou, C. Tsoumakas
¶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‡ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ. ™˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ ÓÂÊÚÔ¿ıÂÈ· ÌÂ Û˘ÁÁÂÓ›˜ ‰È·Ì·Úٛ˜ Ô˘ÚÔÔÈËÙÈÎÔ‡, ÔÊı·ÏÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ 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˘ ¤¯ÂÈ ¯·ÚÙÔÁÚ·ÊËı› ÚfiÛÊ·Ù· ÛÙÔ ¯ÚˆÌfiۈ̷ 9 ÛÙËÓ Ù·ÈÓ›· q34.1. ∫ÔÚ›ÙÛÈ ËÏÈΛ·˜ 4 ¯ÚfiÓˆÓ ÚÔÛ‹Ïı ÁÈ· ¤ÏÂÁ¯Ô ÏfiÁˆ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·˜. ™ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË Î·È ÛÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô Ô˘ ·ÎÔÏÔ‡ıËÛÂ, ÏËÓ Ù˘ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·˜, ‰È·ÈÛÙÒıËÎ·Ó ÂÈϤÔÓ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ, Ï·ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ Î·È Û‡ÁÎ·Ì„Ë ÙˆÓ ·ÁÎÒÓˆÓ. ∆Ô ·ÙÔÌÈÎfi ·Ó·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ, ÂÓÒ ÛÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi, Ë ÌËÙ¤Ú· Ù˘ ·ÛıÂÓÔ‡˜ ›¯Â ˘Ô‚ÏËı› Û ¤̂·ÛË Û ËÏÈΛ· 17 ¯ÚfiÓˆÓ ÏfiÁˆ Û‡Áη̄˘ ·ÁÎÒÓˆÓ. O ·‰Úfi˜ ‚ÈÔ¯ËÌÈÎfi˜, Ô ÂÓ‰Âϯ‹˜ ¤ÏÂÁ¯Ô˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ Î·È Ô ¤ÏÂÁ¯Ô˜ ÁÈ· Û˘ÛÙËÌ·ÙÈ΋ ÓfiÛÔ ‹Ù·Ó ·ÚÓËÙÈÎÔ›. ∏ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËΠ۠¯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›˜ ۯ‰fiÓ Ê˘ÛÈÔÏÔÁÈ΋ ˙ˆ‹. ∞·ÈÙ›ٷÈ, fï˜, Û˘¯Ófi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· ÙÔ ÂӉ¯fiÌÂÓÔ Û˘ÛÙËÌ·ÙÈÎÒÓ ÂΉËÏÒÛˆÓ. O ÚÔÁÂÓÓËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Â›Ó·È ÂÊÈÎÙfi˜, Ë ÙÂÎÓÔÔ›ËÛË fï˜ ·Ôı·ÚÚ‡ÓÂÙ·È Î˘Ú›ˆ˜ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ ÛÔ‚·Ú‹˜ ÓÂÊÚÈ΋˜ ‚Ï¿‚˘.
Abstract: Nail-Patella syndrome (NPS) is a rare autosomal dominant disorder associated with onychodysplasia, antecubital pterygium, hypoplasia or absent patellae, and iliac horns. Nephropathy is often associated with genetic anomalies of the urinary tract, ophthalmic disorders and Goodpasture syndrome. It is the result of a mutation in LMX1B gene, recently mapped in the 9q34.1 chromosomal locus. A 4-year old girl presented with onychodysplasia which on clinical and radiological examination was associated with bilateral antecubital pterygium and absence of patellae. Her previous medical history was insignificant but her mother had a history of antecubital pterygium for which she was operated, during adolescence. The girl’s renal and liver function, and her calcium metabolism were normal. No laboratory evidence of systematic disease was found. She was operated with satisfactory results. Absence of patellae does not cause any disability. The early diagnosis and surgical correction helps patients lead a normal life, nevertheless, frequent tests for systematic complications are needed. Prenatal diagnosis is possible today but childbearing is discouraged mainly because of renal complications.
§¤ÍÂȘ ÎÏÂȉȿ: Nail-Patella, Turner-Kieser, Û‡ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ, ÔÓ˘¯Ô‰˘ÛÏ·Û›·.
Key words: Nail-Patella, Turner-Kieser, antecubital pterygium, onychodysplasia.
¶·È‰È·ÙÚÈÎfi ∆Ì‹Ì·, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∫∞∆, ∞ÙÙÈ΋
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Pediatric Department, KAT General Hospital, Attiki
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14-05-03
14:48
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¶·È‰È·ÙÚÈ΋ 2003;66:140-144
Paediatriki 2003;66:140-144
¶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·ÈÓÔÙ˘Èο ˘ÁÈÒÓ ÁÔÓ¤ˆÓ. ∏ ·ËÛË, Ô ÙÔÎÂÙfi˜ Î·È Ë ÂÚÈÁÂÓÓËÙÈ΋ ÂÚ›Ô‰Ô˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. ∆Ô ·ÙÔÌÈÎfi ÈÛÙÔÚÈÎfi ‹Ù·Ó ÂχıÂÚÔ. ∞fi ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ë ÌËÙ¤Ú· ·ÚÔ˘Û›·˙ ۇ-
ÁÎ·Ì„Ë ·ÁÎÒÓˆÓ, ÁÈ· ÙËÓ ÔÔ›· ¯ÂÈÚÔ˘ÚÁ‹ıËΠ۠ËÏÈΛ· 17 ÂÙÒÓ, ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ ¿Ìʈ Î·È ÔÓ˘¯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·È ÓÂÊÚÈ΋ 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΋ ÂͤÏÈÍË Î·È Ô ¤ÏÂÁ¯Ô˜ ÙˆÓ ˘fiÏÔÈˆÓ Û˘ÛÙËÌ¿ÙˆÓ ‹Ù·Ó Ê˘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·ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ. O ·‰Úfi˜ ‚ÈÔ¯ËÌÈÎfi˜ Î·È Ô ÂÓ‰Âϯ‹˜ ¤ÏÂÁ¯Ô˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ 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 ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ, fiÔ˘ Î·È ÙfiÙ ·ÔÎÏ›ÛÙËΠÓÂÊÚÈ΋, ηډÈÔÏÔÁÈ΋ ‹ ¿ÏÏË Û˘ÛÙËÌ·ÙÈ΋ ¿ıËÛË. ∏ ÎÏÈÓÈ΋ Î·È ·ÂÈÎÔÓÈÛÙÈ΋ ÂÈÎfiÓ· Ù˘ ·ÛıÂÓÔ‡˜ ¤ıÂÛ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ NailPatella. °ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ‰ÂÓ ¤ÁÈÓ ÏfiÁˆ ¿ÚÓËÛ˘ ÙˆÓ ÁÔÓ¤ˆÓ. ∞ÊÔ‡ Ù¤ıËΠÚÔÂÁ¯ÂÈÚËÙÈο ‰˘Ó·ÌÈÎfi˜ Ó¿ÚıËη˜ ¤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 ¤ÁÈÓ ÂÈÌ‹Î˘ÓÛË Î·È ·ÂÏ¢ı¤ÚˆÛË ÙˆÓ ÙÂÓfiÓÙˆÓ ÙˆÓ Î·ÌÙ‹ÚˆÓ ÙÔ˘ ·ÁÎÒÓ·. ªÂÙÂÁ¯ÂÈÚËÙÈο, ÙÔÔıÂÙ‹ıËΠÂÎ Ó¤Ô˘ Ô ›‰ÈÔ˜ ‰˘Ó·ÌÈÎfi˜ Ó¿ÚıËη˜ ÁÈ· 6 Ì‹Ó˜ Î·È ¤ÁÈÓ ÚÔԉ¢ÙÈ΋ ¤ÎÙ·ÛË ÙÔ˘ ·ÁÎÒÓ· ÛÙȘ 165-170 ÌÔ›Ú˜ (∂ÈÎfiÓ· 6). ªÂÙ¿ ÙËÓ ·Ê·›ÚÂÛË ÙÔ˘ Ó¿ÚıËη, Ë ¤ÎÙ·ÛË ÂÚÈÔÚ›ÛÙËΠηٿ 15-
∂ÈÎfiÓ· 1. OÓ˘¯Ô‰˘ÛÏ·Û›·.
∂ÈÎfiÓ· 2. ™˘ÁÁÂÓ‹˜ Û‡ÁÎ·Ì„Ë ·ÁÎÒÓ·.
™˘ÓÙÔÌÔÁڷʛ˜ ¡PS ™‡Ó‰ÚÔÌÔ ¡ail-Patella BM™ µ·ÛÈ΋ ÌÂÌ‚Ú¿ÓË ÛÂÈÚ¿Ì·ÙÔ˜
∂ÈÛ·ÁˆÁ‹ ∆Ô Û‡Ó‰ÚÔÌÔ Nail-Patella (NPS) ‹ “TurnerKieser”, ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·ÚıÚÔ-ÔÓ˘¯Ô-ÔÛÙÂÔ‰˘ÛÏ·Û›·, Â›Ó·È ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ ÓfiÛËÌ·. ™˘Ó‰˘¿˙ÂÈ ÔÓ˘¯Ô‰˘ÛÙÚÔÊ›·, ȉ›ˆ˜ ÛÙÔ˘˜ ·ÓÙ›¯ÂÈÚ˜ (·Ï·Û›·, ηٷÎÂÚÌ·ÙÈÛÌfi, ·Ô¯ÚˆÌ·ÙÈÛÌfi) (90%), Û˘ÁÁÂÓ‹ ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ (60%), Ï·ÁfiÓȘ ÎÂÚ·ÙfiÌÔÚʘ ÂÍÔÛÙÒÛÂȘ (80%) Î·È Û˘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›·Û ÌfiÓÔ ÙȘ ·ÓˆÌ·Ï›Â˜ Ù˘ ÂÈÁÔÓ·Ù›‰·˜, ıˆÚÂ›Ù·È Ô ÚÒÙÔ˜ Ô˘ ÂÚȤÁÚ·„ ÙÔ Û‡Ó‰ÚÔÌÔ, ÂÓÒ Û˘ÓÔÏÈο ̤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÂÚ›Ô˘ 400 ÂÚÈÙÒÛÂȘ. ¶ÚfiÎÂÈÙ·È ÁÈ· Û˘ÁÁÂÓ¤˜ ÓfiÛËÌ·, ÎÏËÚÔÓÔÌÔ‡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·ÊÔÚÂÙÈÎfi ÁÔÓȉ›Ô ˆ˜ ˘Â‡ı˘ÓË ÁÈ· ÙË ÓÂÊÚÔ·ıËÙÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ (12).
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∂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˘ ∑).
20 ÌÔ›Ú˜. ∏ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ·ÛıÂÓÔ‡˜ Û˘Ó¯›ÛÙËΠÁÈ· ÌÂÚÈÎÔ‡˜ Ì‹Ó˜ ·ÎfiÌ· Î·È ÂȂ‚·ÈÒıËÎÂ Ë ÛÙ·ıÂÚÔÔ›ËÛË Ù˘ ¤ÎÙ·Û˘.
ÚˆÓ Ê·Ï¿ÁÁˆÓ (13). ∏ ·Ô˘Û›· ÙˆÓ ÂÈÁÔÓ·Ù›‰ˆÓ ‰ÂÓ ÂËÚ¿˙ÂÈ ÙË ÏÂÈÙÔ˘ÚÁÈ΋ ÈηÓfiÙËÙ· ÙÔ˘ ·ÙfiÌÔ˘, ‰ÂÓ ÂÈÙÚ¤ÂÈ, fï˜, ÙËÓ ¤ÓÙÔÓË ¿ÛÎËÛË Î·È È‰È·›ÙÂÚ· ÙÔÓ ÚˆÙ·ıÏËÙÈÛÌfi. ŸÌˆ˜, Û˘¯Ó¿ ÂÈϤÎÂÙ·È Ì ÔÛÙÂÔ·ÚıÚ›Ùȉ·, Ë ÔÔ›· ÌÔÚ› Ó· Â›Ó·È ‹È· Î·È Ó· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Û˘ÓÙËÚËÙÈο, ÌÔÚ› fï˜ Û¿ÓÈ· Ó· ¯ÚÂÈ·ÛÙ› ·ÚıÚÔÏ·ÛÙÈ΋ ·ÔηٿÛÙ·ÛË (14). ∏ ·ÚÔ˘Û›· ÙˆÓ ˘fiÏÔÈˆÓ ÛÎÂÏÂÙÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ‰ËÌÈÔ˘ÚÁ› ÂÚÈÔÚÈÛÌfi Ù˘ ÎÈÓËÙÈÎfiÙËÙ·˜ ηÈ, ÌÂÚÈΤ˜ ÊÔÚ¤˜, ÛÔ‚·Úfi ·ÈÛıËÙÈÎfi Úfi‚ÏËÌ·. ∏ ·ÛıÂÓ‹˜ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È ·ÚÔ˘Û›·˙Â, ÂÎÙfi˜ ·fi ÙËÓ ÔÓ˘¯Ô‰˘ÛÏ·Û›· (ÁÈ· ÙËÓ ÔÔ›· Î·È ÚÔÛ‹Ïı ÛÙÔ ÓÔÛÔÎÔÌ›Ô), ÙȘ ÂÍ‹˜ ÛÎÂÏÂÙÈΤ˜ ·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 ÌÈÎÚÔÛÎÔÈ΋ ·ÈÌ·ÙÔ˘Ú›·, Ë ÚˆÙÂ˚ÓÔ˘Ú›·, ÙÔ Û‡Ó‰ÚÔÌÔ
™˘˙‹ÙËÛË ∆o NPS Â›Ó·È Û¿ÓÈÔ ÁÂÓÂÙÈÎfi ÓfiÛËÌ· Ô˘ ÂΉËÏÒÓÂÙ·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 Goodpasture. OÈ ÛÎÂÏÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÂΉËÏÒÓÔÓÙ·È Î˘Ú›ˆ˜ ÛÙȘ ÂÈÁÔÓ·Ù›‰Â˜ (·Ô˘Û›· ‹ ˘ÔÏ·Û›·, knockknee), 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-
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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΋ ·Ó¿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˜ ·ÓˆÌ·Ï›Â˜ (ÌÈÎÚÔʷΛ·, ηٷÚÚ¿ÎÙË, ÎÂÚ·ÙfiΈÓÔ, ÁÏ·‡ÎˆÌ·), ÔÏ˘·ÚÙËÚ›Ùȉ·, ÓÔÛ‹Ì·Ù· ÙÔ˘ Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡ (Û. Goodpasture) Î·È Û¯ÈÛٛ˜ (68,16). ¶ÚfiÛÊ·Ù·, ‰ËÌÔÛȇÙËΠÂÚ›ÙˆÛË Á˘Ó·›Î·˜ 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·È ÁÂÓÂÙÈο ·fi Ì›· Ó¤· ÌÂÙ¿ÏÏ·ÍË, Ë ÔÔ›· ÚfiÛÊ·Ù· Èı·ÓÔÏÔÁÂ›Ù·È ˆ˜ ˘Â‡ı˘ÓË (12). ∆Ô ÁÔÓ›‰ÈÔ LMX1B Ú˘ıÌ›˙ÂÈ ¿ÌÂÛ· ÙËÓ ·ÚÔ˘Û›· ÙˆÓ ‚·ÛÈÎÒÓ ÚˆÙÂ˚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›˜ Ì NPS Î·È ÓÂÊÚˆÛÈÎfi Û‡Ó‰ÚÔÌÔ ‹ ¿ÏÏË Û˘Ó‰˘·Ṳ̂ÓË ÓÂÊÚÈ΋ ÓfiÛÔ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi Ù˘ÈΤ˜ ‰ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙË µª™, Ì ÌÂȈ̤ÓË ·ÚÔ˘Û›· ·3 Î·È ·4 ÚˆÙÂ˚ÓÒÓ (18,19). ∏ ‰È¿ÁÓˆÛË ÂȂ‚·ÈÒÓÂÙ·È ·ÂÈÎÔÓÈÛÙÈο Î·È ÁÂÓÂÙÈο. ∏ ·ÚÔ˘Û›· ÔÓ˘¯Ô‰˘ÛÏ·Û›·˜ Î·È ÙÂÚ˘Á›ˆÓ Ì ۇÁη„Ë ÛÙÔ˘˜ ·ÁÎÒÓ˜, ηıÒ˜ Î·È Ô ·ÎÙÈÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÛÙËÓ ·ÛıÂÓ‹ Ì·˜, ÛÙÔÓ ÔÔ›Ô ‰È·ÈÛÙÒıËΠ·Ô˘Û›· ÂÈÁÔÓ·Ù›‰ˆÓ Î·È Ï·ÁfiÓȘ ÂÍÔÛÙÒÛÂȘ, ¤ıÂÛ·Ó ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘. ∏ ·ÚÔ˘Û›· ÙˆÓ Ï·ÁÔÓ›ˆÓ ÂÍÔÛÙÒÛÂˆÓ Â›Ó·È ·ıÔÁÓˆÌÔÓÈÎfi ‡ÚËÌ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘. À¿Ú¯ÂÈ ÛÙÔ 80% 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¤ÂÈ Ó· 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˜ ÂÈÁÔÓ·Ù›‰ˆÓ Î·È Û˘¯Ó¿ Û˘Ó˘¿Ú¯Ô˘Ó ÌÈÎÚÔÁÓ·ı›·, ·ÙÂϤ˜ Ï˘ÎfiÛÙÔÌ·, ÙÂÚ‡ÁÈÔ ÙÚ·¯‹ÏÔ˘, ηÌÙÔ‰·ÎÙ˘-
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Ï›· ‹ Û˘Ó‰·ÎÙ˘Ï›·, ÎÚ˘„ÔÚ¯›·, ÛÎÔÏ›ˆÛË, ·ʈÛË Î·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˘ÛÙËÌ·ÙÈ΋ ÓfiÛÔ (ÎÔÏÏ·ÁfiÓˆÛË, ·ÁÁÂÈ›Ùȉ·, ÔÊı·ÏÌÈ΋ ¿ıËÛË), ‰‡Ó·ÓÙ·È Ó· ·ÔÎÙ‹ÛÔ˘Ó ÌÂÙ¿ ·fi ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË, ‚ÂÏÙ›ˆÛË Ù˘ ÁˆÓ›·˜ ο̄˘ ÙÔ˘ ·ÁÎÒÓ· Î·È Ó· ‰È¿ÁÔ˘Ó Û¯Â‰fiÓ Ê˘ÛÈÔÏÔÁÈÎfi ‚›Ô, ·ÚÎÒ˜ ·˘ÙÔÂ͢ËÚÂÙÔ‡ÌÂÓÔÈ. ∏ ¯Ú‹ÛË Û˘Ó‰˘·Ṳ̂Ó˘ ıÂڷ›·˜ ‰˘Ó·ÌÈÎÒÓ Ó·Úı‹ÎˆÓ ÚÔÂÁ¯ÂÈÚËÙÈο ηÈ, ·ÎÔÏÔ‡ıˆ˜, Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË Ù˘ Û‡Áη̄˘ ÙˆÓ ·ÁÎÒÓˆÓ (fiˆ˜ ¤ÁÈÓ Ì ÙËÓ ·ÛıÂÓ‹ Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È) ÂÈÙ˘Á¯¿ÓÂÈ ÌÂÁ·Ï‡ÙÂÚË ¤ÎÙ˘ÍË (ÂÚ›Ô˘ 155-160 ÌÔ›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¯‹˜ ¿ÛÎËÛË ‰È·Ù·ÙÈÎÒÓ ‰˘Ó¿ÌÂˆÓ ÛÙ· ı˘Ï·ÎÔÛ˘Ó‰ÂÛÌÈο ÛÙÔȯ›· (‰˘Ó¿ÌÂȘ ÂÚ˘ÛÌÔ‡), ÛÙ·ıÂÚÔÔÈ› ÙÔ ¯ÂÈÚÔ˘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¤ÏÂÛÌ· ÚÔ‚ÏËÌ·Ù›˙ÂÈ ÔÏÏÔ‡˜ ·ÛıÂÓ›˜, ¯ˆÚ›˜ fï˜ ̤¯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 ΛӉ˘ÓÔ˜ ·Ó¿Ù˘Í˘ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ Â›Ó·È 25% Î·È ÓÂÊÚÈ΋˜ ·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 Ì ÌÔÚȷ΋ ·Ó¿Ï˘ÛË DNA (21). °ÂÓÈο, Ë ÙÂÎÓÔÔ›ËÛË Û ÔÈÎÔÁ¤ÓÂȘ Ì NPS ·Ôı·ÚÚ‡ÓÂÙ·È ·ÊÂÓfi˜ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ Û˘Ó‡·Ú͢ ÓÂÊÚÈÎÒÓ ‚Ï·‚ÒÓ, ·ÊÂÙ¤ÚÔ˘ ÁÈ· Ó· ÂÚÈÔÚÈÛÙ› Ô ·ÚÈıÌfi˜ ÊÔÚ¤ˆÓ ÓÔÛËÚÒÓ 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΋˜ ÓfiÛÔ˘ ÛÙÔ ¤Ì‚Ú˘Ô, ¯ˆÚ›˜ fï˜ ¿ÓÙ· Ó· Â›Ó·È ‰˘Ó·Ùfi˜ Ô Î·ıÔÚÈÛÌfi˜ Ù˘ Û Ì›˙ÔÓ· ‹ ÂÏ¿ÛÛÔÓ· ÓÂÊÚÈ΋ ‚Ï¿‚Ë. µÈ‚ÏÈÔÁÚ·Ê›· 1. Aschner B. A typical hereditary syndrome: dystrophy of the nails, congenital defect of the patella and congenital defect of the head of radius. JAM∞ 1934;102:2017-2020. 2. Turner JW. A hereditary arthrodysplasia associated with hereditary dystrophy of the nails. JAMA 1993;100:882-884. 3. Cottereill CP, Jacobs P. Hereditary arthro-osteoonychodysplasia associated with iliac horns. Br J Clin Pract 1961;15:933-941.
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4. Leahy MS. The hereditary nephropathy of osteoonychodysplasia. Nail-patella syndrome. Am J Dis Child 1966;112:237-241. 5. Taguchi T, Takebayashi S, Nishimura M, Tsuru N. Nephropathy of nail-patella syndrome. Ultrastruct Pathol 1988;12:175-183. 6. Mark TM, Rywlin AM, Unger H. Cystic adventitial degeneration of the popliteal artery. Its occurrence in a patient with the nail-patella syndrome. Arch Pathol Lab Med 1983;107:186-188. 7. Lichter PR, Richards JE, Downs CA, Stringham HM, Boehnke M, Farley FA. Cosegregation of open-angle glaucoma and the nail-patella syndrome. Am J Ophthalmol 1997;124:506-515. 8. Curtis JJ, Bhathena D, Leach RP, Galla JH, Lucas BA, Luke RG. Goodpasture’s syndrome in a patient with the nailpatella syndrome. Am J Med 1976;61:401-404. 9. Little EM. Congenital absence or delayed development of the 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-patella syndrome locus at 9q34. Am J Hum Genet 1997;60:133142. 11. McIntosh I, Dreyer SD, Clough MV, Dunston JA, Eyaid W, Roig CM et al. Mutation analysis of LMX1B gene in nailpatella syndrome patients. Am J Hum Genet 1998;63:16511658. 12. Chen H, Lun Y, Ovchinnikov D, Kokubo H, Oberg KC, Pepicelli CV et al. Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome. Nat Genet 1998;19:51-55. 13. Jonesk ISH. Recognizable patterns of human congenital malformations. 5 th ed. Philadelphia: Ed Saunders; 1997. p. 438-439. 14. Lachiewicz PF, Herndon CD. Total knee arthroplasty for osteoarthritis in hereditary onycho-osteodysplasia (nail-patella syndrome): a case report. Am J Orthop 1997;26:129-130.
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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 Med Genet 1988;25:682-686. 16. Richieri-Costa A. Antecubital pterygium and cleft lip/palate presenting as signs of the nail-patella syndrome: report of a Brazilian 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 chain disorder. Eur Neurol 2001;46:92-95. 18. Morello R, Zhou G, Dreyer SD, Harvey SJ, Ninomiya Y, Thorner PS et al. Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nat Genet 2001;27:205-208. 19. Rohr C, Prestel J, Heidet L, Hosser H, Kriz W, Johnson RL et al. The LIM-homeodomain transcription factor Lmx1b plays a crucial role in podocytes. J Clin Invest 2002;109:10731082. 20. Goshen E, Schwartz A, Zilka LR, Zwas ST. Bilateral accessory iliac horns: pathognomonic findings in Nailpatella syndrome. Scintigraphic evidence on bone scan. Clin Nucl Med 2000;25:476-477. 21. Pinette MG, Ukleja M, Blackstone J. Early prenatal diagnosis of nail-patella syndrome by ultrasonography. J Ultrasound Med 1999;18:387-389. 22. Gubler MC, Levy M. Prenatal diagnosis of nail-patella syndrome by kidney biopsy. Am J Med Genet 1993;43:693-696.
∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 27-08-2002 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 12-12-2002 ¢È‡ı˘ÓÛË ·ÏÏËÏÔÁÚ·Ê›·˜: ¶··‰ÔÔ‡ÏÔ˘ ∞ıËÓ¿ ¶·È‰È·ÙÚÈÎfi ∆Ì‹Ì·, °.¶.¡. “∫∞∆” ∆.∫. 145 61, ∫ËÊÈÛÈ¿
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Paediatriki 2003;66:145-147
CASE REPORT
§··ÚÔÛÎÔÈ΋ ·ÓÙÈÌÂÙÒÈÛË Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÓÂÔÁÓfi. ¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ∂. ¶··Ó‰Ú¤Ô˘, ∂. µ·ÛÈÏÂÈ¿‰Ô˘, ∂. §ÂÈ‚·‰›ÙË, ∂. °ÎÔ˘ÁÎÔ‡‰Ë, ™. ™˘Ú¿ÎÔ˜, ™. ∞ÚÁ˘ÚÔ‡, ™. ¡ÈÎÔÏ¿Ô˘, ¢. ∫ÂÚ·Ì›‰·˜
Laparoscopic treatment of congenital megacolon in a newborn infant. A case report E. Papandreou, E. Vasiliadou, E. Livaditi, E. Gougoudi, S. Spyrakos, S. Argyrou, S. Nikolaou, D. Keramidas
¶ÂÚ›ÏË„Ë: ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· Û˘Ó‹ıˆ˜ ÂΉËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ·fiÊڷ͢ ÙÔ˘ ÂÓÙ¤ÚÔ˘ Ô˘ ÌÔÚ› Ó· ÂÈϯı› Ì ÂÓÙÂÚÔÎÔÏ›Ùȉ·, Ë ÔÔ›· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Ì Â›ÁÔ˘Û· ÎÔÏÔÛÙÔÌ›·. ∏ ·ÔηٿÛÙ·ÛË Ù˘ Û˘ÁÁÂÓÔ‡˜ ·ÓˆÌ·Ï›·˜ Á›ÓÂÙ·È Û ‰Â‡ÙÂÚÔ ¯ÂÈÚÔ˘ÚÁÈÎfi ¯ÚfiÓÔ. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÚÒÙË ÂÚ›ÙˆÛË ÛÙËÓ ÂÏÏËÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›· ÓÂÔÁÓÔ‡ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, ÙÔ ÔÔ›Ô ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο Û ¤Ó· ¯ÂÈÚÔ˘ÚÁÈÎfi ¯ÚfiÓÔ ¯ˆÚ›˜ ÎÔÏÔÛÙÔÌ›·. ∆Ô ÓÂÔÁÓfi ·ÚÔ˘Û›·Û ÛËÌ›· ÂÓÙÂÚÈ΋˜ ·fiÊڷ͢, fiˆ˜ ›ۯÂÛË ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ Î·È ÌÂÙˆÚÈÛÌfi ÎÔÈÏ›·˜. ¶ÚÔÂÁ¯ÂÈÚËÙÈο ¯ÔÚËÁ‹ıËΠÔÏÈ΋ ·ÚÂÓÙÂÚÈ΋ ‰È·ÙÚÔÊ‹, ·ÓÙÈ‚›ˆÛË Î·È ¤ÁÈÓ ÚÔÂÙÔÈÌ·Û›· ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘. ™ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô ¤ÁÈÓ Ϸ·ÚÔÛÎÔÈ΋ ··ÁÁ›ˆÛË ÙÔ˘ ·ıÔÏÔÁÈÎÔ‡ ÂÓÙ¤ÚÔ˘, ·Ó¿‰ÚÔÌË ‰È·ÚˆÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂÎÙÔÌ‹ 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˜.
Abstract: Congenital megacolon in newborn infants presents clinically as bowel obstruction. In cases complicated by enterocolitis, emergency colostomy is established, followed later by the definitive, second stage, operation. This is the first report in the Greek literature of congenital megacolon in a neonate submitted to laparoscopic operation without preceding colostomy. The neonate presented with intestinal obstruction. Total parenteral nutrition and intravenous antibiotics were given preoperatively and serial bowel washouts were performed. The aganglionic colon was removed laparoscopically and dissection of the rectal mucosa was performed transanally. The ganglionic colon was pulled through the muscular cuff of the rectum and anastomosed above the dentate line, within the muscular cuff. The postoperative course was uncomplicated and bowel function after the operation was normal.
§¤ÍÂȘ ÎÏÂȉȿ: Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, ÓÂÔÁÓfi, Ï··ÚÔÛÎÔÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋.
Key words: congenital megacolon, neonate, laparoscopic surgery.
∂ÈÛ·ÁˆÁ‹ ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· ÂΉËÏÒÓÂÙ·È Ì ÂÈÎfiÓ· ÂÓÙÂÚÈ΋˜ ·fiÊڷ͢. ∞ÓÙÈÌÂÙˆ›˙ÂÙ·È Ì ÂÚ¢ÓËÙÈ΋ Ï··ÚÔÙÔÌ›·, Â¿Ó ‰ÂÓ ˘¿Ú¯ÂÈ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ‰È¿ÁÓˆÛË. ∂Áηı›ÛÙ·Ù·È ÎÔÏÔÛÙÔÌ›· ÎÂÓÙÚÈο Ù˘ ·Á·ÁÁÏȷ΋˜ ‹ ˘ÔÁ·ÁÁÏȷ΋˜ ˙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, ÙÔ 1995, ÂÚȤÁÚ·„·Ó ÙËÓ Ù¯ÓÈ΋ Ï··ÚÔÛÎÔÈ΋˜ ÂÁ¯Â›ÚËÛ˘ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ (2). ª¤¯ÚÈ Û‹ÌÂÚ·, ÂÏ¿¯ÈÛÙ˜ Â›Ó·È ÔÈ ·Ó·ÊÔÚ¤˜ ÛÙË Ï··ÚÔÛÎÔÈ΋ ·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.
µ’ ¶·È‰Ô¯ÂÈÚÔ˘ÚÁÈÎfi TÌ‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó·
2nd Paediatric Surgical Department, “Ag. Sophia” Children’s Hospital, Athens
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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›·˜ ÏfiÁˆ ›ۯÂÛ˘ ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ. ∞fi ÙÔÓ ÎÏÈÓÈÎfi Î·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 ÚÔÂÙÔÈÌ·Û›· ÙÔ˘ ÂÓÙ¤ÚÔ˘, ÙÔ ÂÚȯfiÌÂÓÔ ÙÔ˘ ÔÔ›Ô˘ ÂÎÎÂÓÒıËΠÌÂ Û˘¯Ó¤˜, ·ӷϷ̂·ÓfiÌÂÓ˜ ÙÔÔıÂÙ‹ÛÂȘ ۈϋӷ ·ÂÚ›ˆÓ Î·È Ï‡ÛÂȘ ÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ÔÚfi. ∏ ÂÁ¯Â›ÚËÛË ¤ÁÈÓ Ϸ·ÚÔÛÎÔÈο, ¯ˆÚ›˜ ÎÔÏÔÛÙÔÌ›·. ∏ ¤ÎÙ·ÛË Ù˘ ·Á·ÁÁÏȷ΋˜ Î·È ˘ÔÁ·ÁÁÏȷ΋˜ ˙ÒÓ˘ ηıÔÚ›ÛÙËΠ̠ٷ¯Â›Â˜ ‚ÈÔ„›Â˜ ηٿ ÙË Ï··ÚÔÛÎÔÈ΋ Ê¿ÛË Ù˘ ÂÁ¯Â›ÚËÛ˘ Î·È ·ÊÔÚÔ‡Û ÛÙÔ 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·ÚÔÛÎÔÈο. ÃÚËÛÈÌÔÔÈ‹ıËÎ·Ó 3 trocar, 1 ÁÈ· ÙËÓ Î¿ÌÂÚ· Î·È 2 ÁÈ· Ù· ÂÚÁ·Ï›· ÂÚÁ·Û›·˜. ∏ ›ÂÛË ÙÔ˘ CO2 Î˘Ì¿ÓıËΠ۠›‰· 3-5 mmHg. ∞ÎÔÏÔ‡ıËÛÂ Ô ÂÚÈÓÂ˚Îfi˜ ¯ÚfiÓÔ˜, Ô ÔÔ›Ô˜ ÂÚÈÂÏ¿Ì‚·Ó ·Ó¿‰ÚÔÌË ‰È·ÚˆÎÙÈ΋ ‚ÏÂÓÓÔÁÔÓÂÎÙÔÌ‹ ÙÔ˘ ÔÚıÔ‡ (∂ÈÎfiÓ· 2), ‰ÈÂ΂ÔÏ‹ Î·È Â͈ÙÂڛ΢ÛË ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ ̤ۈ ÙÔ˘ ·Ô‚ÏÂÓÓÔÁÔÓÈṲ̂ÓÔ˘ ÎÔÏÔ‚ÒÌ·ÙÔ˜ ÙÔ˘ ÔÚıÔ‡ (∂ÈÎfiÓ· 3) Î·È ÙÂÏÈÎÔ-ÙÂÏÈ΋ ÎÔÏÔÚˆÎÙÈ΋ ·Ó·ÛÙfïÛË. ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· ÙÔ˘ ÓÂÔÁÓÔ‡ ‹Ù·Ó ÔÌ·Ï‹ Î·È Ë ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÂÓÙ¤ÚÔ˘ ÌÂÙ¿ ÙËÓ ÂÁ¯Â›ÚËÛË Ê˘ÛÈÔÏÔÁÈ΋.
Paediatriki 2003;66:145-147
ÌÂÙˆÚÈÛÌfi ÎÔÈÏ›·˜ Î·È Â›Û¯ÂÛË ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ. ∏ ÙÔÔı¤ÙËÛË ÛˆÏ‹Ó· ·ÂÚ›ˆÓ ÛÙÔ ÔÚıfi ÂÍÔ˘‰ÂÙÂÚÒÓÂÈ ÙË Û‡Û·ÛË ÙÔ˘ ·Á·ÁÁÏÈ·ÎÔ‡ ̤ÚÔ˘˜ Î·È ·ÎÔÏÔ˘ıÂ›Ù·È ·fi ÂÎÚËÎÙÈ΋ ·Ô‚ÔÏ‹ ·ÂÚ›ˆÓ Î·È ÎÔÚ¿ÓˆÓ, ÂÊfiÛÔÓ Ô ÛˆÏ‹Ó·˜ ¤¯ÂÈ Ì‹ÎÔ˜ fiÛÔ Î·È ÙÔ - Û ۇ۷ÛË - ¤ÓÙÂÚÔ (3). ™˘¯Ó‹ ÂÈÏÔ΋ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· Â›Ó·È Ë ÂÓÙÂÚÔÎÔÏ›ÙȘ, Ë ÔÔ›· ··ÈÙ› ›ÁÔ˘Û· ÎÔÏÔÛÙÔÌ›·. ∏ ¤ÁηÈÚË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘, Ë ÔÔ›· Á›ÓÂÙ·È Ì ÙËÓ ÎÏÈÓÈ΋ ÂÎÙ›ÌËÛË, ÙË ‚ÈÔ„›· ÙÔ˘ ÔÚıÔ‡ Î·È ÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô, Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÚfiÏË„Ë Ù˘ ÂÓÙÂÚÔÎÔÏ›Ùȉ·˜ Î·È ÛÙËÓ ·ÏÏ·Á‹ ÛÙÚ·ÙËÁÈ΋˜ ˆ˜ ÚÔ˜ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ™ÙË Û˘ÁÎÂÎÚÈ̤ÓË ÂÚ›ÙˆÛË, ¤ÁÈÓ ‰È·ÎÔ‹ Ù˘ Û›ÙÈÛ˘, ÙÔÔı¤ÙËÛË ÚÈÓÔÁ·ÛÙÚÈÎÔ‡ ۈϋӷ, ¯ÔÚ‹ÁËÛË ÔÏÈ΋˜ ·ÚÂÓÙÂÚÈ΋˜ ‰È·ÙÚÔÊ‹˜ Î·È ÂÓ‰ÔÊϤ‚È·˜ ·ÓÙÈ‚›ˆÛ˘, ηıÒ˜ ηÈ
™˘˙‹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˘˜,
∂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˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘, ¤¯Ô˘Ó ÂÊ·ÚÌÔÛÙ› ÂÈÙ˘¯Ò˜ Ì Ϸ·ÚÔÙÔÌ›· ‰È¿ÊÔÚ˜ Ù¯ÓÈΤ˜, ·fi ÙȘ Ôԛ˜ ÔÈ ÂÈÎÚ·Ù¤ÛÙÂÚ˜ Â›Ó·È ÔÈ Ù¯ÓÈΤ˜ Swenson, Duhamel Î·È Soave-Boley (4-7). ¶ÚfiÛÊ·Ù·, ÔÈ Georgeson 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¿ ÙËÓ ÂÌÂÈÚ›· Ô˘ ·ÔÎÙ‹ıËΠÛÙȘ Ï··ÚÔÛÎÔÈΤ˜ ÂÁ¯ÂÈÚ‹ÛÂȘ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÂÈÚ·Ì·Ùfi˙ˆ·, ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο ·È‰› ËÏÈΛ·˜ 14 ÂÙÒÓ ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ, Ì ¿ÚÈÛÙÔ ÌÂÙÂÁ¯ÂÈÚËÙÈÎfi ·ÔÙ¤ÏÂÛÌ· (9,10). ™ÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹, Ë ›ÂÛË ÙÔ˘ CO2 ÛÙËÓ ÂÚÈÙÔÓ·˚΋ ÎÔÈÏfiÙËÙ· ‹Ù·Ó 10±2 mmHg. ∏ ÂÌÂÈÚ›· ·˘Ù‹ ·ÍÈÔÔÈ‹ıËΠηÈ, ¤ÙÛÈ, ¯ÂÈÚÔ˘ÚÁ‹ıËΠϷ·ÚÔÛÎÔÈο ÓÂÔÁÓfi ÌÂ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ ¯ˆÚ›˜ ȉȷ›ÙÂÚË ‰˘ÛÎÔÏ›·.
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4. Swenson O, Bill AH. Resection of the rectum and rectosigmoid with preservation of the sphincter for benign spastic lesions producing megacolon. Surgery 1948;24:212-220. 5. Duhamel B. A new operation for the treatment of Hirschsprung’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 primary anastomosis for Hirschsprung’s disease in infants and children. J Paediatr Surg 1995;30:1017-1022. 8. Georgeson KE, Cohen RD, Hebra A, Jona JZ, Powell DM, Rothenberg SS et al. Primary laparoscopic-assisted endorectal colon pull-through for Hirschsprung’s disease: a new 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 Soave ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Û˘ÁÁÂÓÔ‡˜ ÌÂÁ¿ÎÔÏÔ˘ Û ÂÈÚ·Ì·ÙÈÎfi ÌÔÓÙ¤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΋ ¯ÂÈÚÔ˘ÚÁÈ΋ ÛÙÔ Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ: ¶ÂÚ›ÙˆÛË ·È‰ÈÔ‡ ËÏÈΛ·˜ 14 ÂÙÒÓ. ∂ÏÏËÓÈ΋ ÃÂÈÚÔ˘ÚÁÈ΋ (˘fi ¤Î‰ÔÛË).
µÈ‚ÏÈÔÁÚ·Ê›· 1. Teitelbaum DH, Qualman SJ, Caniano DA. Hirschsprung’s disease. Identification of risk factors for enterocolitis. Ann Surg 1988;207:240-244. 2. Georgeson KE, Fuenfer MM, Hardin WD. Primary laparoscopic pull-through for Hirschsprung’s disease in infants and children. J Pediatr Surg 1995;30:1017-1022. 3. ∫ÂÚ·Ì›‰·˜ ¢. ∆Ô Û˘ÁÁÂÓ¤˜ ÌÂÁ¿ÎÔÏÔ. π·ÙÚÈ΋ 1978; 34:497-507.
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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∂¡¢π∞º∂ƒOÀ™∞ ¶∂ƒπ¶∆ø™∏
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CASE REPORT
∫˘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
¶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 ÂÚÈÙÒÛÂȘ ÓÂÔÁÓÒÓ Ì ™∫∞¢¶, ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο ÙÂÎÌËÚȈ̤Ó˜. ¶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¿ÁÓˆÛË ¤ÁÈÓ Û ̛· ÂÚ›ÙˆÛË. ªÂÙ¿ ÙË Á¤ÓÓËÛË, Ë ‰È¿ÁÓˆÛË ‚·Û›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È ÛÙ· Â˘Ú‹Ì·Ù· ÙÔ˘ ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂϤÁ¯Ô˘ (·ÎÙÈÓÔÁÚ·Ê›· ıÒڷη, ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›·). ¢ÂÓ ˘‹Ú¯·Ó ¿ÏϘ Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜. ™Â fiÏ· Ù· ÓÂÔÁÓ¿ ¤ÁÈÓ ¯ÂÈÚÔ˘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·ÙÔÌÈ΋ ÂͤٷÛË, fiÔ˘ ‰È·ÈÛÙÒıËΠfiÙÈ ‰‡Ô ·fi ÙȘ ÂÚÈÙÒÛÂȘ Ì·˜ ·Ó‹Î·Ó ÛÙÔÓ Ù‡Ô 1 Î·È Ì›· ÛÙÔÓ Ù‡Ô 4 Ù˘ ÓfiÛÔ˘. ∏ ÂͤÏÈÍË ‹Ù·Ó ηϋ Û ‰‡Ô ·fi ·˘Ù¿ Ù· ÓÂÔÁÓ¿, ÂÓÒ ¤Ó· η٤ÏËÍ ÌÂÙÂÁ¯ÂÈÚËÙÈο ·fi ÛË„·ÈÌ›·.
Abstract: Congenital cystic adenomatoid malformation (CCAM) of the lung constitutes a rare but serious cause of neonatal respiratory distress. Three cases of histologically confirmed CCAM in newborn infants, two female and one male are reported. Two presented with respiratory distress immediately after birth and one at one month of age. In one case, the condition had been diagnosed prenatally. Postnatally, the diagnosis was made on the basis of the clinical features and the findings on radiological investigation (chest X-ray, computerized tomography). No other congenital anomalies were found. All three neonates underwent lobectomy shortly after diagnosis. The diagnosis was confirmed by histological examination, which revealed that two cases belonged to type 1 and one to type 4 CCAM. Two of the infants had a good outcome, whereas one died of sepsis in the immediate postoperative period.
§¤ÍÂȘ ÎÏÂȉȿ: ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›· Ó‡ÌÔÓ·, Û˘ÁÁÂÓ›˜ ·ÛÙÂȘ.
Key words: adenomatoid malformation of the lung, congenital cysts.
∂ÈÛ·ÁˆÁ‹ ∏ Û˘ÁÁÂÓ‹˜ ΢ÛÙÈ΋ ·‰Âӈ̷Ù҉˘ ‰˘ÛÏ·Û›· ÙÔ˘ Ó‡ÌÔÓ· (™∫∞¢¶) ·ÔÙÂÏ› Û¿ÓÈ· ‰˘ÛÏ·Û›· ÙˆÓ Ó¢ÌfiÓˆÓ, ÌÂ Û˘¯ÓfiÙËÙ· Ô˘ ˘ÔÏÔÁ›˙ÂÙ·È Û 1 ÂÚ›ÙˆÛË ·Ó¿ 25000-35000 ΢‹ÛÂȘ (1). ÷ڷÎÙËÚ›˙ÂÙ·È ·fi ÙË ‰ËÌÈÔ˘ÚÁ›· ·ÛÙÂˆÓ ÔÈΛÏÔ˘ 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˜ ÌÂÏÂÙÒÓÙ·˜ 38 ÂÚÈÙÒÛÂȘ ™∫∞¢¶, ͯÒÚÈÛ 3 Ù‡Ô˘˜ (π-πππ), ·Ó¿ÏÔÁ· Ì ÙË ‰È¿ÌÂÙÚÔ ÙˆÓ Î‡ÛÙÂˆÓ Î·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
¡ÂÔÁÓÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞ÚÈÛÙÔÙ¤ÏÂÈÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·ÏÔӛ΢, πÔÎÚ¿ÙÂÈÔ °¶¡ £ÂÛÛ·ÏÔӛ΢
Department of Neonatology of Aristotelion University of Thessaloniki, “Ippokration” General Hospital, Thessaloniki
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Paediatriki 2003;66:148-154
(·ÛÙÂȘ >2 cm) (4). ŸÏÔÈ ÔÈ ·Ú·¿Óˆ Ù‡ÔÈ ·ÓÙÈÛÙÔÈ¯Ô‡Û·Ó Û ‰˘ÛÏ·Û›· ÙÔ˘ ‚ÚÔÁ¯ÈÎÔ‡ ‰¤Ó‰ÚÔ˘, ·fi ÙÔ˘˜ ÌÂÁ¿ÏÔ˘˜ ‚ÚfiÁ¯Ô˘˜ ̤¯ÚÈ Ù· ÙÂÏÈο ‚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, Ë ÔÔ›· Û˘ÌÂÚÈÂÏ¿Ì‚·Ó 5 Ù‡Ô˘˜ (Ù‡ÔÈ 0-4) (¶›Ó·Î·˜ 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 ÙÂÎÌËÚȈ̤Ó˜ 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› ÚÔÁÂÓÓËÙÈο Ì 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¤ÓÓËÛË, Ë ÓfiÛÔ˜ ÂΉËÏÒÓÂÙ·È Û˘Ó‹ıˆ˜ ÛÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô Î·È Ì¿ÏÈÛÙ· ÙȘ ÚÒÙ˜ ÒÚ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË, Ì ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·. ªÂÙ¿ ÙË ÓÂÔÁÓÈ΋ ÂÚ›Ô‰Ô, ÌÔÚ› Ó· ÂΉËψı› Ì ‚‹¯· Î·È ˘ÔÙÚÔÈ¿˙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˘ÌÌ·) ‹ ·fi ¿ÏÏ· fiÚÁ·Ó·, fiˆ˜ Â›Ó·È ÔÈ ÓÂÊÚÔ› (ÓÂÊÚÈ΋ ·ÁÂÓÂÛ›·, ‰˘ÛÁÂÓÂÛ›·, ΢ÛÙÈ΋ ÓfiÛÔ˜ ÙˆÓ ÓÂÊÚÒÓ), Ë Î·Ú‰È¿, Ù· ÔÛÙ¿, ÙÔ ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡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 ÓÂÔÁÓ¿ Ô˘ ÓÔÛËχÙËÎ·Ó ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Î·È Á›ÓÂÙ·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜. ¶ÂÚÈÁÚ·Ê‹ ÂÚÈÙÒÛÂˆÓ ¶ÂÚ›ÙˆÛË 1Ë ¡ÂÔÁÓfi ÎÔÚ›ÙÛÈ, Ì ËÏÈΛ· ·ËÛ˘ (∏∫) 36 ‚‰ÔÌ¿‰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·ÌÓËÛÙÈÎfi ‹Ù·Ó ÂχıÂÚÔ ÁÈ· ‰˘ÛϷۛ˜ Ó‡ÌÔÓ· ‹ Û˘ÁÁÂÓ›˜ ·ÛÙÂȘ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ Î·È ‰ÂÓ ˘‹Ú¯Â ÈÛÙÔÚÈÎfi ¤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‹ ·ÎÙÈÓÔÁÚ·Ê›· ıÒڷη ¤‰ÂÈÍ ¢ÌÂÁ¤ıË Î‡ÛÙË ÛÙÔ ‰ÂÍÈfi Ó¢ÌÔÓÈÎfi ‰›Ô, ¯ˆÚ›˜ ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ (∂ÈÎfiÓ· 1). ¢ÂÓ ˘‹Ú¯·Ó ÂÌÊ·Ó›˜ ‰˘ÛϷۛ˜, ÂÓÒ Ô ˘ÂÚ˯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÂÁÎÂÊ¿ÏÔ˘, ηډȿ˜ Î·È ÓÂÊÚÒÓ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜. ∏ ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ·ÓÙÈÌÂÙˆ›ÛÙËΠ·Ú¯Èο Ì ¯ÔÚ‹ÁËÛË Ô͢ÁfiÓÔ˘ Î·È ÙË 16Ë Ë̤ڷ ˙ˆ‹˜ ÙÔ ÓÂÔÁÓfi ˘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‰ÚÈÎfi ÎÚÔÛÛˆÙfi 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 3Ë ÌÂÙÂÁ¯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¤ÁÂıÔ˜ ·ÛÙÂˆÓ (cm)
0,5
10
2,5
2
7
¢Ô̤˜ Ô˘ ÌÔÈ¿˙Ô˘Ó Ì ‚ÚfiÁ¯Ô˘˜. ∫ÚÔÛÛˆÙfi, ΢ÏÈÓ‰ÚÈÎfi ÂÈı‹ÏÈÔ ÌÂ Î·Ï˘ÎÔÂȉ‹ ·ÙÙ·Ú·
¶ÔÏ˘ÏÔ‚Ò‰ÂȘ, ÌÂÁ¿Ï˜ ·ÛÙÂȘ Ì ÈÓÒ‰Ë ‰È·ÊÚ¿ÁÌ·Ù·. ∫ÚÔÛÛˆÙfi ΢ÏÈÓ‰ÚÈÎfi ÂÈı‹ÏÈÔ Ì ‚ÏÂÓÓÔ·Ú·ÁˆÁ¿ ·ÙÙ·Ú·
ªÈÎÚ¤˜, ÔÌÔÈfiÌÔÚʘ ·ÛÙÂȘ Ô˘ ÌÔÈ¿˙Ô˘Ó Ì ‰È·ÙÂٷ̤ӷ ÙÂÏÈο ‚ÚÔÁ¯ÈfiÏÈ·. ∫ÚÔÛÛˆÙfi ΢‚ÔÂȉ¤˜ ‹ ΢ÏÈÓ‰ÚÈÎfi ÂÈı‹ÏÈÔ
™˘Ì·Á›˜, ÔÁÎÒ‰ÂȘ ‚Ï¿‚˜ Ì ÌÈÎÚ¤˜ ·ÂÚÔÊfiÚ˜ ·ÛÙÂȘ. ∫ÚÔÛÛˆÙfi, ΢‚ÔÂȉ¤˜ ÂÈı‹ÏÈÔ
¶ÔÏ˘ÏÔ‚Ò‰ÂȘ, ÌÂÁ¿Ï˜ ÂÚÈÊÂÚÈΤ˜ ·ÛÙÂȘ. ∫˘„ÂÏȉÈο ·ÙÙ·Ú· Ù‡Ô˘ π
¡·È
5%-10% ÙˆÓ ÂÚÈÙÒÛˆÓ
Ÿ¯È
Ÿ¯È
Ÿ¯È
ªÈÎÚÔÛÎÔÈ΋ ÂÌÊ¿ÓÈÛË
ÃfiÓ‰ÚÔ˜
149
MARC-APR 03
14-05-03
14:49
™ÂÏ›‰·150
¶·È‰È·ÙÚÈ΋ 2003;66:148-154
∂ÈÎfiÓ· 1. (¶ÂÚ›ÙˆÛË 1) ∂˘ÌÂÁ¤ı˘ ·ÛÙË ÛÙÔ ‰ÂÍÈfi Ó¢ÌÔÓÈÎfi ‰›Ô, ¯ˆÚ›˜ ·ÚÂÎÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘.
¶ÂÚ›ÙˆÛË 2Ë ¡ÂÔÁÓfi ÎÔÚ›ÙÛÈ, Ì ∏∫ 36 ‚‰ÔÌ¿‰Â˜ Î·È µ° 2900 g, ‰È·ÎÔÌ›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙË Á¤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 ‰ÂÍÈfi Ó‡ÌÔÓ·, ¯ˆÚ›˜ ¿ÏÏ· ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∫·Ù¿ ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË ‰ÂÓ ‰È·ÈÛÙÒıËÎ·Ó ÂÌÊ·Ó›˜ Û˘ÁÁÂÓ›˜ ‰˘ÛϷۛ˜. ™ÙËÓ ·Ï‹ ·ÎÙÈÓÔÁÚ·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. ∆Ș ÂfiÌÂÓ˜ Ë̤Ú˜ ·Ú·ÙËÚ‹ıËΠ˘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¿ (∂ÈÎfiÓ· 2‚). ∆Ë 17Ë Ë̤ڷ ˙ˆ‹˜, ÙÔ ÓÂÔÁÓfi ˘Ô‚Ï‹ıËΠ۠ıˆÚ·ÎÔÙÔÌ‹ Î·È ÏÔ‚ÂÎÙÔÌ‹ ÙÔ˘ ‰ÂÍÈÔ‡ ¿Óˆ Î·È Ì¤ÛÔ˘ ÏÔ‚Ô‡. ™ÙËÓ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËÎ·Ó Ì›· ¢ÌÂÁ¤ı˘ ·ÛÙË ÛÙÔÓ ‰ÂÍÈfi ̤ÛÔ ÏÔ‚fi Î·È ‰‡Ô ÌÈÎÚfiÙÂÚ˜ ÛÙÔÓ ‰ÂÍÈfi ¿Óˆ ÏÔ‚fi, Ô˘ ÂÚÈ‚¿ÏÏÔÓÙ·Ó ·fi ΢„ÂÏ›‰Â˜ ‚ÚfiÁ¯Ô˘˜ Î·È ‚ÚÔÁ¯ÈfiÏÈ· Î·È Î·Ï‡ÙÔÓÙ·Ó ·fi ÎÚÔÛÛˆÙfi ΢ÏÈÓ‰ÚÈÎfi ÂÈı‹ÏÈÔ, Â˘Ú‹Ì·Ù· Û˘Ì‚·Ù¿ Ì ÙÔÓ Ù‡Ô 1 ™∫∞¢¶. ∆Ô ÓÂÔÁÓfi ·Ú¤ÌÂÈÓ Û Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi ÁÈ· 7 Ë̤Ú˜. ∫ÏÈÓÈο, Ë ·Ó·Ó¢-
150
Paediatriki 2003;66:148-154
ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚËÛ ÙÂÏ›ˆ˜ Î·È ÛÙËÓ ·ÎÙÈÓÔÁÚ·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‰Ô Î·È Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 4 ¯ÚfiÓˆÓ ‰ÂÓ ·ÚÔ˘Û›·Û ·Ó·Ó¢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΋, ÙÔ ÔÈÎÔÁÂÓÂÈ·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·ÎÔÏÔ‡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 ¿ÏϘ ÎÏÈÓÈΤ˜ ÂӉ›ÍÂȘ ‰˘ÛÌÔÚÊÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘. ™ÙËÓ ·Ï‹ ·ÎÙÈÓÔÁÚ·Ê›· ıÒڷη ‰È·ÈÛÙÒıËΠ‰È¿¯˘ÙË ‰ÈÎÙ˘ÔÎÔÎÎ҉˘ ·ÂÈÎfiÓÈÛË ÙˆÓ Ó¢ÌfiÓˆÓ Ì ·ÂÚÔ‚ÚÔÁ¯fiÁÚ·ÌÌ·, ‰›¯ˆ˜ ¿ÏÏ· ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∆¤ıËÎÂ Ë ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ Î·È ·ÓÙÈÌÂÙˆ›ÛÙËΠ̠¯ÔÚ‹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 Î·È ÙÔ 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·ÙfiÈÛË ÙÔ˘ 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, ·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· (∂ÈÎfiÓ· 3‚). ∆ËÓ 34Ë Ë̤ڷ Ù˘ ˙ˆ‹˜ ÙÔ˘, ÙÔ ÓÂÔÁÓfi ˘Ô‚Ï‹ıËΠ۠¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË, fiÔ˘ ¤ÁÈÓ ÂÎÙÔÌ‹ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ¿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 ÏÂÙfi ÈÓÔÌ˘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, ÙÔ ÓÂÔÁÓfi ·Ú¤ÌÂÈÓ Û Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi ÁÈ· 5 Ë̤Ú˜. ∫ÏÈÓÈο, Ë ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· ˘Ô¯ÒÚËÛ ÙÂÏ›ˆ˜ Î·È ÛÙÔÓ ·ÎÙÈÓÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ‰È·ÈÛÙÒıËΠÛÙ·‰È·Î‹ ¤ÎÙ˘ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ οو ÏÔ‚Ô‡
MARC-APR 03
14-05-03
14:49
™ÂÏ›‰·151
¶·È‰È·ÙÚÈ΋ 2003;66:148-154
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Paediatriki 2003;66:148-154
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∂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˜ η٤Ϸ‚ ÔÏfiÎÏËÚË ÙË ‰ÂÍÈ¿ ıˆÚ·ÎÈ΋ ÎÔÈÏfiÙËÙ·.
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∂ÈÎfiÓ· 3. (¶ÂÚ›ÙˆÛË 3) ·) ÀÂڤ΢ÍË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ Ó‡ÌÔÓ· Ì ÔÏ˘Î˘ÛÙÈ΋ ·ÂÈÎfiÓÈÛË, ÌÂÙ·ÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ‰ÂÍÈ¿ 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˘.
Î·È Î·Ù¿ÏË„Ë Ù˘ ·ÚÈÛÙÂÚ‹˜ ıˆÚ·ÎÈ΋˜ ÎÔÈÏfiÙËÙ·˜ (∂ÈÎfiÓ· 3Á). ªÂÙ¿ ÙËÓ ¤ÍÔ‰Ô ·fi ÙËÓ ÎÏÈÓÈ΋ Î·È Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 8 ÌËÓÒÓ, ‰ÂÓ ·ÚÔ˘Û›·Û ·Ó·Ó¢ÛÙÈο ÚÔ‚Ï‹Ì·Ù·. ™˘˙‹ÙËÛË OÈ ÂÚÈÙÒÛÂȘ ™∫∞¢¶ Ô˘ ÂÚÈÁÚ¿ÊÔ˘Ì ¤¯Ô˘Ó Ù· ÂÍ‹˜ ¯·Ú·ÎÙËÚÈÛÙÈο: ·) Û ̛· ÌfiÓÔ ÂÚ›ÙˆÛË ˘‹Ú¯Â ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË, ·Ó Î·È ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÂÌ‚Ú‡Ô˘ ¤ÁÈÓ Û fiϘ ÙȘ ÂÚÈÙÒÛÂȘ, ‚) fiϘ ÂΉËÏÒıËÎ·Ó ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, Á) Û η̛· ‰ÂÓ ˘‹Ú¯·Ó ‰˘ÛϷۛ˜ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ Î·È ‰) ÔÈ ‰‡Ô ÂÚÈÙÒÛÂȘ ‹Ù·Ó Ù‡Ô˘ 1 Î·È Ë Ì›· Ù‡Ô˘ 4. ∏ ·ıÔÁ¤ÓÂÈ· Ù˘ ™∫∞¢¶ ‰ÂÓ Â›Ó·È Ï‹Úˆ˜ ÁÓˆÛÙ‹. Œ¯ÂÈ ıˆÚËı› ˆ˜ ·Ì¿Úو̷, ÂÓÙÔÈṲ̂ÓË ‰˘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 Î·È Û˘Ó, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ·ÓÔÛÔ˚ÛÙÔ¯ËÌÈΤ˜ ÌÂıfi‰Ô˘˜, ÌÂϤÙËÛ·Ó ÙÔÓ Ù‡Ô ÙˆÓ Î˘ÙÙ¿ÚˆÓ 22 ÂÚÈÙÒÛÂˆÓ ™∫∞¢¶ Î·È ÙÔÓ Û˘Û¯¤ÙÈÛ·Ó Ì ÙËÓ ·ıÔÁ¤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¿ÛÂȘ Ù˘ 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˘Í˘ ÙˆÓ ‚ÚfiÁ¯ˆÓ ̤¯ÚÈ Ù· ÙÂÏÈο ‚ÚÔÁ¯ÈfiÏÈ· (pseudocanalicular stage) Î·È ÔÈ Î‡ÛÙÂȘ ηχÙÔÓÙ·È ·fi ÂÈı‹ÏÈÔ ‚ÚÔÁ¯ÈÎÔ‡ Ù‡Ô˘. O Ù‡Ô˜ 4 ÔÊ›ÏÂÙ·È Û ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ Î˘„ÂÏ›‰ˆÓ (saccular stage) Î·È ÔÈ Î‡ÛÙÂȘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÈı‹ÏÈÔ Î˘„ÂÏȉÈÎÔ‡ Ù‡Ô˘ (6,13). ∏ ™∫∞¢¶ ÌÔÚ› Ó· ‰È·ÁÓˆÛÙ› Ì ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÙÔ˘ ÂÌ‚Ú‡Ô˘ ·fi ÙË 17Ë Â‚‰ÔÌ¿‰· Ù˘ ·ËÛ˘ (3,12,14-16). ªÂ ‚¿ÛË Ù· ˘ÂÚ˯ÔÁÚ·ÊÈο
151
MARC-APR 03
14-05-03
14:49
™ÂÏ›‰·152
¶·È‰È·ÙÚÈ΋ 2003;66:148-154
Paediatriki 2003;66:148-154
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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 ÙÔÓ Stocker (2). ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÙÔ˘ ÂÌ‚Ú‡Ô˘ Â›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˘ ˘ÂÚ˯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·ÙfiÈÛË ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘ ·ÔÙÂÏÔ‡Ó ‰˘ÛÌÂÓ›˜ ÚÔÁÓˆÛÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ (1-3,11,15,17,18). øÛÙfiÛÔ, Ë ÚÔÁÂÓÓËÙÈ΋ ηıÔ‰‹ÁËÛË Ú¤ÂÈ Ó· Á›ÓÂÙ·È Ì ÌÂÁ¿ÏË ÚÔÛÔ¯‹, ÁÈ·Ù› ˘¿Ú¯ÂÈ ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi Ï·Óı·Ṳ̂Ó˘ ‰È¿ÁÓˆÛ˘ ‹ ·˘ÙfiÌ·Ù˘ ‡ÊÂÛ˘. OÈ McCullagh Î·È Û˘Ó ·Ú·ÎÔÏÔ‡ıËÛ·Ó ÁÈ· ‰È¿ÛÙËÌ· 25 ÌËÓÒÓ 13 ÂÚÈÙÒÛÂȘ Ì ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶ Î·È ‰È·›ÛÙˆÛ·Ó fiÙÈ Ë ÓfiÛÔ˜ ÂȂ‚·ÈÒıËΠÌfiÓÔ ÛÙÔ 54% (16). ∂ÈϤÔÓ, ÔÈ Laberge Î·È Û˘Ó, Û ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË 48 ÂÚÈÙÒÛÂˆÓ Ì ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶, ‚Ú‹Î·Ó fiÙÈ ÛÙÔ 56% ÔÈ Î‡ÛÙÂȘ ˘Ô¯ÒÚËÛ·Ó ÛËÌ·ÓÙÈο Û ̤ÁÂıÔ˜ ‹ ÂÍ·Ê·Ó›ÛÙËÎ·Ó Ì¤¯ÚÈ ÙË Á¤ÓÓËÛË (1). ∫·È ¿ÏÏÔÈ Û˘ÁÁÚ·Ê›˜ ·Ó·Ê¤ÚÔ˘Ó ·˘ÙfiÌ·ÙË ÛÌ›ÎÚ˘ÓÛË ‹ ÂÍ·Ê¿ÓÈÛË ÙˆÓ Î‡ÛÙÂˆÓ Ô˘ ‰È·ÁÓÒÛÙËÎ·Ó ÚÔÁÂÓÓËÙÈο, Û ÔÛÔÛÙ¿ Ô˘ Î˘Ì·›ÓÔÓÙ·È ·fi 18% ̤¯ÚÈ 85% (10,11,15,19). °È’ ·˘Ùfi, ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ 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‹-
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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·ÛË ÙˆÓ Î‡ÛÙÂˆÓ Â›Ó·È ‰˘Ó·ÙfiÓ, ›Ù ·˘ÙfiÌ·Ù· ›Ù ÏfiÁˆ 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˘ÛÈÔÏÔÁÈÎÒÓ ÏÔ‚ÒÓ ÙÔ˘ Ó‡ÌÔÓ·, Ô˘ Ô‰ËÁÔ‡Ó Û ·ÈÊÓ›‰È· Âȉ›ӈÛË Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜, fiˆ˜ Û˘Ó¤‚Ë ÛÙË 2Ë Î·È 3Ë ÂÚ›ÙˆÛË. ™Â fiϘ ÙȘ ÂÚÈÙÒÛÂȘ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘, Ë ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘ ‚·Û›ÛÙËΠÛÙ· Â˘Ú‹Ì·Ù· Ù˘ ·ÎÙÈÓÔÁÚ·Ê›·˜ ıÒڷη, fiÔ˘ ‰È·ÈÛÙÒıËÎ·Ó Î‡ÛÙÂȘ ÔÈΛÏÔ˘ ÌÂÁ¤ıÔ˘˜ ÁÂÌ¿Ù˜ Ì ·¤Ú·. ™·ÓÈfiÙÂÚ·, ÔÈ ÌÈÎÚÔ΢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¤ÂÈ Ó· Á›ÓÂÙ·È Î·È ÛÙȘ ÂÚÈÙÒÛÂȘ fiÔ˘ Ë ÂÓ‰ÔÌ‹ÙÚÈ· ·Ú·ÎÔÏÔ‡ıËÛË ¤‰ÂÈÍ ÛÌ›ÎÚ˘ÓÛË ‹ ÂÍ·Ê¿ÓÈÛË ÙˆÓ 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 ÌfiÓÔ Ì 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 ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË, Ë ÔÔ›· Û˘Ó›ÛÙ·Ù·È Û ÏÔ‚ÂÎÙÔÌ‹ ‹ ÙÌËÌ·ÙÂÎÙÔÌ‹ (11,12,15). °È· Ù· ·Û˘Ìو̷ÙÈο 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
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¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË ·ÚÁfiÙÂÚ·, ÌÂÙ¿ ÙËÓ ËÏÈΛ· ÙˆÓ 6 ÌËÓÒÓ (11). O ÚÔÙÂÈÓfiÌÂÓÔ˜ ·ÏÁfiÚÈıÌÔ˜ ÁÈ· ÙË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÓÂÔÁÓÒÓ Ì ÚÔÁÂÓÓËÙÈ΋ ‰È¿ÁÓˆÛË ™∫∞¢¶ Ê·›ÓÂÙ·È ÛÙÔÓ ¶›Ó·Î· 2. ¶¿ÓÙˆ˜, fiÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ·fiÊ·ÛË ÁÈ· ÙÔ ¯ÚfiÓÔ Ù˘ ¤̂·Û˘, Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È ˘’ fi„ÈÓ ÔÈ Î›Ó‰˘ÓÔÈ ·fi ÙËÓ Î·ı˘ÛÙÂÚË̤ÓË ·Ê·›ÚÂÛË Ù˘ ‚Ï¿‚˘, fiˆ˜ Â›Ó·È Ë Û˘Ì›ÂÛË ÙˆÓ Ó¢ÌfiÓˆÓ, ÔÈ ÏÔÈÌÒÍÂȘ, ·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˜ ÛÙËÓ Ó¢ÌÔÓÈ΋ ˘ÔÏ·Û›· ‹ ÛÙȘ ÛÔ‚·Ú¤˜ Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ Ô˘ Û˘Ó˘¿Ú¯Ô˘Ó (1,10,21). ∏ Û˘¯ÓfiÙËÙ· Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ Â›Ó·È ÌÂÁ¿ÏË ÛÙË ™∫∞¢¶ Ù‡Ô˘ 2, ÂÚ›Ô˘ 20% (7-50%) Î·È ÌÈÎÚfiÙÂÚË 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¯fiÓÙˆÓ Û˘ÁÁÂÓÒÓ ‰È·Ì·ÚÙÈÒÓ. ™Â Ì›· ÌfiÓÔ ·fi ÙȘ ‰ËÌÔÛÈÂ˘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 ηϋ. ∞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 ÂÌʇÛËÌ· (26). ™Ô‚·Ú‹ ÂÈÏÔ΋ Ì·ÎÚÔÚfiıÂÛÌ· ·ÔÙÂÏ› Ë “˘ÔÏÂÈÌÌ·ÙÈ΋” ™∫∞¢¶, ‰ËÏ·‰‹ Ë fi„ÈÌË ÂÌÊ¿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·ÈÚ¤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› Û¿ÓÈ· ·ÈÙ›· ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ·, ··ÈÙ› ¿ÌÂÛË ·Ó·ÁÓÒÚÈÛË, ηıÒ˜ ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ¤¯ÂÈ Î·Ï‹ ÚfiÁÓˆÛË 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 diagnosed congenital cystic adenomatoid lung malformation: a
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18. Bunduki V, Ruano R, da Silva MM, Miguelez J, Miyadahira S, Maksoud JG et al. Prognostic factors associated with congenital 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 congenital cystic adenomatoid malformation of the lung: a report of 26 cases and review of the literature. Ultrasound Obstet Gynecol 2000;16:159-162. 20. Dommergues M, Louis-Sylvestre C, Mandelbrot L, Aubry MC, Revillon Y, Jarreau PH et al. Congenital adenomatoid malformation of the lung: when is active fetal therapy indicated? 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 the lung: current management and prognosis. J Pediatr Surg 1991;26:975-980. 22. Marshall KW, Blane CE, Teitelbaum DH, van Leeuwen K. Congenital cystic adenomatoid malformation: impact of prenatal diagnosis and changing strategies in the treatment of the asymptomatic patient. Am J Roentgenol 2000;175:1551-1554.
23. dell’Agnola C, Tadini B, Mosca F, Colnaghi M, Wesley J. Advantages of prenatal diagnosis and early surgery for congenital cystic disease of the lung. J Perinat Med 1996;24:621-631. 24. Shariff S, Thomas JA, Shetty N, D’Cunha S. Primary pulmonary rhabdomyosarcoma in a child, with a review of literature. J Surg Oncol 1988;38:261-264. 25. Sheffield EA, Addis BJ, Corrin B, McCabe MM. Epithelial hyperplasia and malignant change in congenital lung cysts. J Clin Pathol 1987;40:612-614. 26. Frenckner B, Freyschuss U. Pulmonary function after lobectomy for congenital lobar emphysema and congenital cystic adenomatoid malformation. A follow-up study. Scand J 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›ÎË E-mail: agaki@med.auth.gr
¶ÂÚ›ÏË„Ë ¿ÚıÚÔ˘ ·fi ÙË µÈ‚ÏÈÔÁÚ·Ê›· ª·ÎÚÔ¯ÚfiÓÈ· ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜ Û ‚Ú¤ÊË, Ì ÙÔÈ΋ ÂÊ·ÚÌÔÁ‹ pimecrolimus1 ∂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 Â›‰Ú·ÛË Ù˘ ÚÒÈÌ˘ ıÂڷ¢ÙÈ΋˜ ·Ú¤Ì‚·Û˘ Ì Îڤ̷ pimecrolimus ÛÙË Ì·ÎÚÔ¯ÚfiÓÈ· ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘. ™ÎÔfi˜: ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ó· ·ÍÈÔÏÔÁ‹ÛÂÈ ·Ó Ë ÚÒÈÌË 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‹ ÌÂϤÙË, ‰È¿ÚÎÂÈ·˜ ÂÓfi˜ ¤ÙÔ˘˜, Û 251 ‚Ú¤ÊË ËÏÈΛ·˜ 3-23 ÌËÓÒÓ Ô˘ 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·ÎÙÈÎÒÓ ÁÈ· ÙËÓ ÍËÚÔ‰ÂÚÌ›· Î·È ÙÔÈÎÒÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ Ù˘ ÓfiÛÔ˘. ™ÙËÓ ÂÚ›ÙˆÛË ÚÒÈÌˆÓ ÛËÌ›ˆÓ Î·È Û˘ÌÙˆÌ¿ÙˆÓ ‰ÂÚÌ·Ù›Ùȉ·˜, ¯ÚËÛÈÌÔÔÈ‹ıËΠÎڤ̷ pimecrolimus ‹ ÌfiÓÔ ¤Î‰Ô¯Ô. ∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ÂÊ·ÚÌÔ˙fiÌÂÓ˘ ·ÁˆÁ‹˜ ÂÎÙÈÌ‹ıËΠ̠‚¿ÛË ÙËÓ Â›ÙˆÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ ÛÙÔ˘˜ 6 Ì‹Ó˜ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂڷ›·˜. ∞ÔÙÂϤÛÌ·Ù·: ¢È·ÈÛÙÒıËΠfiÙÈ ÙÔ pimecrolimus Ô‰‹ÁËÛ Û ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÂÍ¿ÚÛÂˆÓ Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜ Î·È ‹Ù·Ó ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈÎfi ÛÙÔÓ Ì·ÎÚÔ¯ÚfiÓÈÔ ¤ÏÂÁ¯Ô ÙÔ˘ ÎÓËÛÌÔ‡ Î·È ÙˆÓ ˘fiÏÔÈˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Ù˘ ÓfiÛÔ˘, Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘, Ì ÔÛÔÛÙfi 67,6% ÙˆÓ
154
·ÛıÂÓÒÓ Ó· ÔÏÔÎÏËÚÒÓÂÈ ÙÔ ÂÍ¿ÌËÓÔ Ù˘ ÌÂϤÙ˘ ¯ˆÚ›˜ η̛· ¤Í·ÚÛË, Û ۯ¤ÛË Ì 34,8% ÙˆÓ Ì·ÚÙ‡ÚˆÓ (p<0,001), ÂÓÒ 56,9% ¤Ó·ÓÙÈ 28,3%, ·ÓÙ›ÛÙÔȯ·, ¯ˆÚ›˜ ¤Í·ÚÛË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÂÓfi˜ ¤ÙÔ˘˜. ∂ÈϤÔÓ, Ë ¯Ú‹ÛË ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÛÙËÓ 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 ÛËÌ›ˆÓ Ù˘ ·ÙÔÈ΋˜ ‰ÂÚÌ·Ù›Ùȉ·˜. ¢ÂÓ ˘‹Ú¯·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·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› Ó· ·ÏÏ¿ÍÂÈ ÛËÌ·ÓÙÈο ÙËÓ ÔÚ›· Ù˘ ÓfiÛÔ˘, ÌÂÈÒÓÔÓÙ·˜ ÙȘ ÂÍ¿ÚÛÂȘ Î·È ‚ÂÏÙÈÒÓÔÓÙ·˜ ÙÔÓ ÁÂÓÈÎfi ¤ÏÂÁ¯Ô Ù˘ ÓfiÛÔ˘. ∆Ô pimecrolimus ‹Ù·Ó ·ÛʷϤ˜ Î·È Î·Ï¿ ·ÓÂÎÙfi.
1 Kapp A, Papp K, Bingham A, Folster-Holst R, Ortonne JP, Potter PC et al Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid antiinflammatory drug J Allergy Clin Immunol 2002;110:277-284
∂ϤÓË µÔÏÔÓ¿ÎË
MARC-APR 03
14-05-03
14:49
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¶·È‰È·ÙÚÈ΋ 2003;66:155-162
∂¶π∫∞πƒ∞ £∂ª∞∆∞
Paediatriki 2003;66:155-162
CURRENT ISSUES
§Â˘ÎÔÙÚȤÓÈ· Î·È ÊÏÂÁÌÔÓ‹: ÓÂfiÙÂÚË Ê·ÚÌ·ÎÔÏÔÁÈ΋ ıÂÒÚËÛË ∞. ∆˘ÏÈÁ¿‰·, °. ∞ÓÙˆÓÔÁÂÒÚÁÔ˜
Leukotrienes and inflammation: current pharmacological perspective ∂. Tiligada, G. Antonogeorgos
¶ÂÚ›ÏË„Ë: ∆· Ï¢ÎÔÙÚȤÓÈ· (L∆s) Â›Ó·È ÂÓ‰ÔÁÂÓ›˜ ÏÈȉÈÎÔ› ÌÂÛÔÏ·‚ËÙ¤˜ Ô˘ Û˘ÓÙ›ıÂÓÙ·È de novo 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·‰ÈηÛÈÒÓ Î·È ÛÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈÛÙ‹. OÌ·‰ÔÔÈÔ‡ÓÙ·È Û ΢ÛÙÂ˚Ó˘ÏÈο ·Ó¿ÏÔÁ· (cys-LTs) Î·È ÛÙÔ LTB4 Î·È ·ÛÎÔ‡Ó ÙË ‰Ú¿ÛË ÙÔ˘˜ ̤ۈ ‰È·ÎÚÈÙÒÓ ˘ÔÙ‡ˆÓ ˘Ô‰Ô¯¤ˆÓ. ™ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· Ê·ÚÌ·ÎÔÏÔÁÈο ¯·Ú·ÎÙËÚÈÛÙÈο 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 ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ.
Abstract: Leukotrienes (L∆s) are endogenous lipid mediators, which are synthesised de novo via intercellular metabolic processes, through the 5lipoxygenase pathway. ∆hey are involved in the pathogenesis of asthma and other inflammatory processes and in the host defence response. They are sub-grouped into cysteinyl-LTs (cys-LTs) and LTB4 and exert their action via distinct receptors. This review presents the pharmacological characteristics of the synthesis, metabolism and action of LTs, the properties of their receptors and the clinical application of the leukotriene modifiers.
§¤ÍÂȘ ÎÏÂȉȿ: Ï¢ÎÔÙÚȤÓÈ·, ˘Ô‰Ô¯Â›˜, ÙÚÔÔÔÈËÙ¤˜.
Key words: leukotrienes, receptors, modifiers.
™˘ÓÙÔÌÔÁڷʛ˜ AIA BLT cPLA2 cysLT(s) FLAP GPCR 5-HpETE IL 5-LO LT(s) MAP MAPK ORF PAF PGE2 ROS SRS
ÕÛıÌ· ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË ·ÛÈÚ›Ó˘ ÀÔ‰Ô¯¤·˜ ÙÔ˘ Ï¢ÎÔÙÚÈÂÓ›Ô˘ µ4 ∫˘ÙÔÛÔÏÈ΋ ʈÛÊÔÏÈ¿ÛË ∞2 ∫˘ÛÙÂ˚Ó˘ÏÈÎfi(¿) Ï¢ÎÔÙÚȤÓÈÔ(·) ¶ÚˆÙ½ÓË ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘ ÀÔ‰Ô¯¤·˜ Û˘Ó‰ÂfiÌÂÓÔ˜ Ì ڈÙ½Ó˜ G 5-˘‰ÚÔÂÚÔ͢-ÂÈÎÔÛ·ÙÂÙÚ·ÓÔ˚Îfi Ô͇ πÓÙÂÚÏ¢ΛÓË 5-ÏÈÔ͢ÁÂÓ¿ÛË §Â˘ÎÔÙÚȤÓÈÔ(·) ¶ÚˆÙ½ÓË ÂÓÂÚÁÔÔÈÔ‡ÌÂÓË ·fi ÌÈÙÔÁfiÓ· ∫ÈÓ¿ÛË Ù˘ ª∞ƒ ¶Ï·›ÛÈÔ ·Ó¿ÁÓˆÛ˘ ¶·Ú¿ÁÔÓÙ·˜ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ¶ÚÔÛÙ·ÁÏ·Ó‰›ÓË ∂2 ∂ÓÂÚÁ¿ ·Ú¿ÁˆÁ· Ô͢ÁfiÓÔ˘ µÚ·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›·
∂ÚÁ·ÛÙ‹ÚÈÔ º·ÚÌ·ÎÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ
SRS-A 7TM TNF
µÚ·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›· Ù˘ ·Ó·Ê˘Ï·Í›·˜ ∂Ù¿ ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ ÂÚÈÔ¯¤˜ 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›Ԣ˜ Ì˘˜ (1). ∂›ÎÔÛÈ ¯ÚfiÓÈ· ·ÚÁfiÙÂÚ·, ÌÂÙÔÓÔÌ¿ÛÙËΠ۠‚Ú·‰¤ˆ˜-·ÓÙȉÚÒÛ· Ô˘Û›· Ù˘ ·Ó·Ê˘Ï·Í›·˜ (SRS-A, slow-reacting substance of anaphylaxis), ÂÂȉ‹ Ë ·Ú·ÁˆÁ‹ Ù˘ Û¯ÂÙÈ˙fiÙ·Ó Ì ÙËÓ ·ÂÏ¢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· Î·È Laboratory of Pharmacology, Medical School of University of Athens
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ÂÚÈ›¯Â ¤Ó· Û˘˙¢Á̤ÓÔ ÙÚȤÓÈÔ (3). ∆Ô LTC ‹Ù·Ó ÙÔ ÂÈÎÔÛ·ÓÔÂȉ¤˜ Ô˘ Ù·˘ÙÔÔÈ‹ıËΠ(3), ÂÓÒ ÙËÓ ›‰È· ÂÔ¯‹ ·ÔÌÔÓÒıËÎÂ Î·È ÙÔ LTB4 ·fi Ù· ÔÏ˘ÌÔÚÊÔ‡ÚËÓ· Ï¢ÎÔ·ÙÙ·Ú· (4). ª¤¯ÚÈ Û‹ÌÂÚ·, Ë ÂÚ¢ÓËÙÈ΋ ÚÔÛ¿ıÂÈ· ÛÙÔÓ ÙÔ̤· ·˘Ùfi ÂÈÎÂÓÙÚÒıËΠÛÙÔ ÌÂÛÔÏ·‚ËÙÈÎfi ÚfiÏÔ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ ÛÙÔ ¿ÛıÌ· ηÈ, ÁÂÓÈÎfiÙÂÚ·, ÛÙȘ ·ÓÙȉڿÛÂȘ ˘ÂÚ¢·ÈÛıËÛ›·˜ 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·È ÛÙË ‰È·Î˘ÙÙ¿ÚÈ· ÂÈÎÔÈÓˆÓ›· ηٿ ÙË ÊÏÂÁÌÔÓÒ‰Ë ·¿ÓÙËÛË Î·È ÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈÛÙ‹ (6,7). ∆· Ï¢ÎÔÙÚȤÓÈ· ÔÌ·‰ÔÔÈÔ‡ÓÙ·È Ì ‚¿ÛË ÙË ¯ËÌÈ΋ ‰ÔÌ‹ Î·È ÙË ‚ÈÔÏÔÁÈ΋ ÙÔ˘˜ ‰Ú¿ÛË Û ‰‡Ô ÔÌ¿‰Â˜, Ë Ì›· ÂÎ ÙˆÓ ÔÔ›ˆÓ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ ÚÔÊÏÂÁÌÔÓ҉˜ ‰È¸‰ÚÔ͢-Ï¢ÎÔÙÚȤÓÈÔ LTB4 Î·È Ë ¿ÏÏË Ù· ÂÙȉÔÏÈȉÈο ‹ ÛÔ˘ÏÊȉÈο ‹ ΢ÛÙÂ˚Ó˘ÏÈο Ï¢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·ÙÔÔÈÂ›Ù·È ÛÙËÓ ˘ÚËÓÈ΋ ÌÂÌ‚Ú¿ÓË. ∆· Ï¢ÎÔÙÚȤÓÈ· ‰ÂÓ ·ÔıË·ÔÓÙ·È ÛÙ· ·ÙÙ·Ú·, ·ÏÏ¿ ‚ÈÔÛ˘ÓÙ›ıÂÓÙ·È de novo (∂ÈÎfiÓ· 1) (5,8), fiÙ·Ó Ë Ca2+-ÂÍ·ÚÙÒÌÂÓË Î˘ÙÔÛÔÏÈ΋ ʈÛÊÔÏÈ¿ÛË ∞2 (cPLA2) ÌÂÙ·ÙÔ›˙ÂÙ·È ÛÙÔÓ ˘ÚËÓÈÎfi Ê¿ÎÂÏÔ ÌÂÙ¿ ·fi ‰È¤ÁÂÚÛË Î·È ·ÂÏ¢ıÂÚÒÓÂÈ ·Ú·¯È‰ÔÓÈÎfi Ô͇ ·fi Ù· ÌÂÌ‚Ú·ÓÈο ʈÛÊÔÏÈ›‰È· (9). µ·ÛÈÎfi ÚfiÏÔ ÛÙÔ Û¯ËÌ·ÙÈÛÌfi ÙˆÓ LTs ·›˙ÂÈ Ë 5-ÏÈÔ͢ÁÂÓ¿ÛË (5LO), 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 (mitogenactivated protein kinase), ÌÂÙ·ÙÔ›˙ÂÙ·È ÛÙÔÓ ˘ÚËÓÈÎfi Ê¿ÎÂÏÔ, ·Á΢ÚÔ‚ÔÏ› ÛÙË ÌÂÌ‚Ú¿ÓË Î·È Ì¤Ûˆ Ù˘ ÚˆÙ½Ó˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ 5-ÏÈÔ͢ÁÂÓ¿Û˘ (FLAP) ÌÂÙ·ÙÚ¤ÂÈ ÙÔ ·Ú·¯È‰ÔÓÈÎfi Ô͇ ·Ú¯Èο Û 5-˘‰ÚÔ͢-ÂÚÔ͢-ÂÈÎÔÛ·ÙÂÙÚ·ÓÔ˚Îfi Ô͇ (5HpETE) Î·È Î·ÙfiÈÓ ÙÔ ·Ê˘‰·ÙÒÓÂÈ Û LT∞4 (5,6ÔÍÂȉÔ-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˜ Û LTµ4 ‹ LTC4 (12). ™Ù· ÎÔÎÎÈÔ·ÙÙ·Ú· (ˈÛÈÓfiÊÈÏ·, ‚·ÛÂfiÊÈÏ·, ÛÈÙ¢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·ıÂÈfiÓË (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
156
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LTD4, ÙÔ ÔÔ›Ô Ì ÙË ÛÂÈÚ¿ ÙÔ˘ ‰È·Û¿Ù·È ·fi ÂÍˆÎ˘ÙÙ¿ÚȘ ÂÙȉ¿Û˜ ÛÙÔ ‚ÚÔÁ¯ÔÛ˘Û·ÛÙÈÎfi Î·È ·ÁÁÂÈÔ‰Ú·ÛÙÈÎfi LT∂4 (8). ™Ù· ÌÔÓÔ·ÙÙ·Ú·, Ì·ÎÚÔÊ¿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‰ÒÓ ÂÚÂıÈÛÌ¿ÙˆÓ (4,7,16-19). ∏ LTA4 ˘‰ÚÔÏ¿ÛË ·ÂÓÂÚÁÔÔÈÂ›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˘Ó ÙËÓ ·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·ÙÔÔÈÂ›Ù·È Ì ‰È·Î˘ÙÙ¿ÚÈÔ ÌÂÙ·‚ÔÏÈÛÌfi ˘fi Ê˘ÛÈÔÏÔÁÈΤ˜ Î·È ·ıÔÏÔÁÈΤ˜ Û˘Óı‹Î˜ (6,21,22). ™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ, Ù· ÔÈÔÙÈο Î·È ÔÛÔÙÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ Û¯ËÌ·ÙÈ˙fiÌÂÓˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ ÂÍ·ÚÙÒÓÙ·È ·fi ÙËÓ ÈηÓfiÙËÙ· ÙˆÓ Ô˘‰ÂÙÂÚfiÊÈÏˆÓ Ó· 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‰ÔıËÏȷο ·ÙÙ·Ú· (21) Û˘Óı¤ÙÔ˘Ó LTC4 Î·È LTB4 ·fi ÙÔ 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¿ÁˆÁ¿ ÙÔ˘˜ (·Ú¿ÁˆÁ· ˆ- Î·È ‚-ÔÍ›‰ˆÛ˘, Ù· ÔÔ›· ·ÓȯÓ‡ÔÓÙ·È ÛÙ· Ô‡Ú·) Â›Ó·È ‚ÈÔÏÔÁÈÎÒ˜ ‰Ú·ÛÙÈο ÚÔ˚fiÓÙ· (24). ∆Ô LTB4 ηٷ‚ÔÏ›˙ÂÙ·È Ì ‰È¿ÊÔÚÔ˘˜ 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 ÌÈÎÚÔÛˆÌȷ΋ ˆ-ÔÍ›‰ˆÛË Ì¤Ûˆ ÙˆÓ ˆ-˘‰ÚÔÍ˘Ï·ÛÒÓ ÙÔ˘ ΢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˘ÂÏÔÂȉ‹ ·ÙÙ·Ú· Î·È Ù· Ë·ÙÔ·ÙÙ·Ú· Ì ˘ÂÚÔÍ˘ÛˆÌȷ΋ ‚-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. ™‡Ìʈӷ 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) Î·È ÌÂÙ·‚¿ÏÏÔ˘Ó ÙË ‰È·ÂÚ·ÙfiÙËÙ· ÙˆÓ ·ÁÁ›ˆÓ ηÈ
MARC-APR 03
14-05-03
14:49
™ÂÏ›‰·157
¶·È‰È·ÙÚÈ΋ 2003;66:155-162
Paediatriki 2003;66:155-162
PL
KÔÚÙÈÎÔÛÙÂÚÔÂȉ‹
Ca
AÓ·ÛÙÔÏ›˜ FLAP
Ca
AA
FLAP
Ca
cPLA2
cPLA2
¶˘Ú‹Ó·˜
2+
Ca2+ Ca
5-LOX
5-LOX Ca
2+
2+
TH2 ΢ÙÔΛÓ˜ IgE º¿Ú̷η
2+
2+
LTC4
AÓ·ÛÙÔÏ›˜ 5-LOX
A
LTA4
LTC4 Û˘ÓıÂÙ¿ÛË
EÚ˘ıÚÔ·ÙÙ·ÚÔ
LTA4 ˘‰ÚÔÏ¿ÛË
GSH
AÓ·ÛÙÔÏ›˜ ˘‰ÚÔÏ¿Û˘
LTB4
LTB4
LTC4
LTA4
T
LTC4
LTB4
LTB4
LTC4 LTD4
LTB4 ·ÓÙ·ÁˆÓÈÛÙ¤˜ ˘Ô‰Ô¯¤ˆÓ
‰ÈÂÙȉ¿ÛË Gly
EÓ‰ÔıËÏÈ·Îfi ·ÙÙ·ÚÔ
Á-ÁÏÔ˘Ù·Ì˘ÏÙÚ·ÓÛÊÂÚ¿ÛË Glu
BLT
LTE4
C
LTF4
ys
LT
1
Glu HˆÛÈÓfiÊÈÏÔ §ÂÌÊÔ·ÙÙ·ÚÔ
∂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-ÏÈÔ͢ÁÂÓ¿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 Î·È LT∂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∞4 Ô˘ ·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).
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˘ÛÈÔÏÔÁ›· ÙÔ˘ ¿ÛıÌ·ÙÔ˜. ™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ·Ó·ÊÔÚ¤˜, Ë Î·ÙËÁÔÚÈÔÔ›ËÛË ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ cysLTs ‚·Û›˙ÂÙ·È ÛÙȘ Ê·ÚÌ·ÎÔÏÔÁÈΤ˜ ȉÈfiÙËÙ˜ ÙˆÓ ·ÓÙ·ÁˆÓÈÛÙÒÓ, ÂÓÒ ‰ÂÓ ·ÔÎÏ›ÂÙ·È ÂÚ·ÈÙ¤Úˆ ÂÙÂÚÔÁ¤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 ÂȉÒÓ (25). ª¤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó ¯·Ú·ÎÙËÚÈÛÙ› ‰‡Ô ηÙËÁÔڛ˜ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ cysLTs, Ô˘ ·Ó‹ÎÔ˘Ó ÛÙÔ˘˜ “˘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, ÔÈ cysLT3, 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˘ÔÛˆÌÈ·ÎÒÓ ÂÓ˙‡ÌˆÓ Î·È ÂÓÂÚÁÒÓ ·Ú·ÁÒÁˆÓ Ô͢ÁfiÓÔ˘ (ROS, reactive oxygen species) ·fi Ù· ÎÔÎÎÈÔ·ÙÙ·Ú· Î·È Ù· Ì·ÎÚÔÊ¿Á· (16,23,27). ¶ÚfiÎÂÈÙ·È ÁÈ· ÙÔ Î‡ÚÈÔ ÚÔ˚fiÓ ÙˆÓ Ô˘‰ÂÙÂÚfiÊÈÏˆÓ Î·È Ì·ÎÚÔÊ¿ÁˆÓ Î·È ‰È·ı¤ÙÂÈ ÙËÓ ÈηÓfiÙËÙ· ·Ó¿ÎÙËÛ˘ Î·È ÂÓÂÚÁÔÔ›ËÛ˘ ¢ڤˆ˜ Ê¿ÛÌ·ÙÔ˜ ·ÓÔÛÔÏÔÁÈÎÒÓ ÌÂÛÔÏ·‚ËÙÒÓ (20). ¶ÂÚÈÁÚ¿ÊÂÙ·È ˆ˜ ÈÛ¯˘Úfi˜ ¯ËÌÂÈÔÙ·ÎÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜, Ô ÔÔ›Ô˜ Û˘ÌÌÂÙ¤¯ÂÈ ÛÙËÓ ¤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˘‰ÂÙÂÚfiÊÈψÓ, ̤ۈ ‰‡Ô ÂÈÊ·ÓÂÈ·ÎÒÓ ˘Ô‰Ô¯¤ˆÓ (¶›Ó·Î·˜
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¶›Ó·Î·˜ 1. ÷ڷÎÙËÚÈÛÙÈο ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ Î˘ÛÙÂ˚Ó˘ÏÈÎÒÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ (25,65-67) CysLT2
CysLT1 ™˘ÁÁ¤ÓÂÈ·: LTD4 > LTC4 > LTE4
™˘ÁÁ¤ÓÂÈ·: LTC4 = LTD4>> LTE4 ∞ÓÙ·ÁˆÓÈÛÙ¤˜
BAYu9773 (ÌË ÂÎÏÂÎÙÈÎfi˜), MK571 CGP45715∞ (ÈÚ·ÏÔ˘Î¿ÛÙË), LY170680 ICI204219 (˙·ÊÈÚÏÔ˘Î¿ÛÙË) MK476 (ÌÔÓÙÂÏÔ˘Î¿ÛÙË) ONO1078 (Ú·ÓÏÔ˘Î¿ÛÙË) Ro24-5913 (ÛÈÓ·ÏÔ˘Î¿ÛÙË), ZK3523 SKF104353 (ÔÌÈÏÔ˘Î¿ÛÙË)
BAYu9773 (ÌË ÂÎÏÂÎÙÈÎfi˜)
∫·Ù·ÓÔÌ‹ ÛÙÔÓ ¿ÓıÚˆÔ §Â›Â˜ 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· 38% ÔÌÔÏÔÁ›· Ì ÙÔÓ cysLT1 28% ÔÌÔÏÔÁ›· Ì ÙÔÓ BLT1 ªÂÙ·‚›‚·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·
2), ÙÔÓ ˘„ËÏ‹˜ Û˘ÁÁ¤ÓÂÈ·˜ µLT1 (12) Î·È ÙÔÓ ¯·ÌËÏ‹˜ Û˘ÁÁ¤ÓÂÈ·˜ µLT2 (28). OÈ ‰‡Ô ˘ÔÙ‡ÔÈ ·Ó‹ÎÔ˘Ó ÛÙÔ˘˜ “˘Ô‰Ô¯Â›˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ڈÙ½Ó˜ 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·˙fiÌÂÓË ¤ÎÊÚ·ÛË (29,30). ∂›Ó·È ÂӉȷʤÚÔÓ fiÙÈ Ô ˘ÔÎÈÓËÙ‹˜ 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˘ Έ‰ÈÎÔÔÈÔ‡Ó ˘Ô‰Ô¯Â›˜ Ï¢ÎÔÙÚÈÂÓ›ˆÓ, ·ÏÏ¿ Î·È ¿ÏÏˆÓ ¯ËÌÂÈÔÂÏÎÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Î·Ù¿ ÙË ‰È·‰Èηۛ· Ù˘ ÂͤÏÈ͢, ηıÒ˜ Î·È Ë ÁÂÓˆÌÈ΋ ÔÚÁ¿ÓˆÛË Ù˘ ÁÔÓȉȷ΋˜ ı¤Û˘ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ LTB4 ÛÙÔ ·ÓıÚÒÈÓÔ ¯ÚˆÌfiۈ̷ 14 (19,31,32). Œ¯ÂÈ, ›Û˘, ÂÚÈÁÚ·Ê› Ô ˘ÚËÓÈÎfi˜ ˘Ô‰Ô¯¤·˜ PPAR· (peroxisome proliferator-activated receptor), ÛÙÔÓ ÔÔ›Ô ÚÔÛ‰¤ÓÂÙ·È ÙÔ LTB4 Î·È ÂÓÂÚÁÔÔÈ› 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 ÚfiÏÔ ÛÙË ÊÏÂÁÌÔÓÒ‰Ë ·¿ÓÙËÛË Ô˘ Û˘Óԉ‡ÂÈ ÙÔ ¿ÛıÌ·, Ù· ·ÙÔÈο ÓÔÛ‹Ì·Ù· Î·È ÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈ-
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ÛÙ‹ ηٿ ÙËÓ ÂÈÛ‚ÔÏ‹ Í¤ÓˆÓ ÚÔ˜ ÙÔÓ ÔÚÁ·ÓÈÛÌfi Ô˘ÛÈÒÓ (8,25). ∏ ηٷÓÔÌ‹ ÙˆÓ ·Ó·‚ÔÏÈÎÒÓ ÂÓ˙‡ÌˆÓ Û ‰È¿ÊÔÚ· ·ÙÙ·Ú· ηıÈÛÙ¿ ÙË ‰È·Î˘ÙÙ¿ÚÈ· ÌÂÙ·ÊÔÚ¿ ÙÔ˘˜ Ô˘ÛÈ·ÛÙÈ΋ Û fi,ÙÈ ·ÊÔÚ¿ ÛÙË ‚ÈÔÛ‡ÓıÂÛË Î·È ÂÈÎÔÈÓˆÓ›· ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ (6,21,22). ∆· cysLTs, LTC4 Î·È LTD4 Â›Ó·È ‚ÚÔÁ¯ÔÛ˘Û·ÛÙÈÎÔ› ·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·ÓÙȉڷÛÙÈÎfiÙËÙ·, ÙËÓ ¤ÎÎÚÈÛË ‚ϤÓÓ˘ Î·È ÙËÓ ·fiÊÚ·ÍË ÙˆÓ ·ÂÚ·ÁˆÁÒÓ Û ·ÛıÌ·ÙÈÎÔ‡˜ ·ÛıÂÓ›˜ (8). ¶·Ú¿ÏÏËÏ·, Ù· cysLTs ÚÔ¿ÁÔ˘Ó ÙË ÌÂÙ·Ó¿ÛÙ¢ÛË ËˆÛÈÓÔÊ›ÏˆÓ ÛÙÔ˘˜ ·ÂÚ·ÁˆÁÔ‡˜ ·ÛıÌ·ÙÈÎÒÓ ·ÛıÂÓÒÓ. ∆· ·ÙÙ·Ú· Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙȘ ·ÓÙȉڿÛÂȘ ˘ÂÚ¢·ÈÛıËÛ›·˜ Ù‡Ô˘ π ‰È·ı¤ÙÔ˘Ó Ì˯·ÓÈÛÌfi Û‡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 ËˆÛÈÓÔÊ›ÏˆÓ Ó· ·ÂÏ¢ıÂÚÒÓÔ˘Ó ÙÔÍÈΤ˜ ‚·ÛÈΤ˜ ÚˆÙ½Ó˜ Î·È LTC4 (14), Ô ÚfiÏÔ˜ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ‰ÂÓ Â›Ó·È Î·Ù·ÓÔËÙfi˜, ·Ú’ fiÏÔ Ô˘ ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ˘˜ ·ÂÚ·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΋ ÛËÌ·Û›· ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ ÛÙÔ ¿ÛıÌ· ·ÌÊÈÛ‚ËÙÂ›Ù·È (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˘ ÁÔÓȉÈÒÌ·ÙÔ˜ Ô˘ ¤¯Ô˘Ó Û˘Ó‰Âı› Ê·ÈÓÔÙ˘Èο Ì ÙÔ
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¶›Ó·Î·˜ 2. ÷ڷÎÙËÚÈÛÙÈο ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘ LTB4 (12,19,28,30,32,68,69) µLT2
µLT1 ∞ÓÙ·ÁˆÓÈÛÙ¤˜ CP105696, U75302, CP195543, O¡O4057
LY255283, ZK158252, O¡O4057 ∫·Ù·ÓÔÌ‹
∫˘Ú›ˆ˜ ÂÚÈÊÂÚÈο Ï¢ÎÔ·ÙÙ·Ú· Î·È ÂÚÈÙÔÓ·˚ο Ì·ÎÚÔÊ¿Á·, ¯·ÌËÏ‹ ¤ÎÊÚ·ÛË ÛÙÔ ı‡ÌÔ Î·È ÛÏ‹Ó·
∂˘Ú›· ¤ÎÊÚ·ÛË Î˘Ú›ˆ˜ ÛÙÔ ÛÏ‹Ó· ◊·Ú, ˆÔı‹ÎË, Ï¢ÎÔ·ÙÙ·Ú·, ηډȿ, ÓÂÊÚÔ›, 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 BLT1 ƒ‡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˘ LTB4 Ca2+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
¿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 ·Ó·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 ¯ÔÚ‹ÁËÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÔÊ›ÏÂÙ·È ÛÙËÓ ·Ó·ÛÙÔÏ‹ Ù˘ ·fiÙˆÛ˘ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÏfiÁˆ Ù˘ ·˘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›ËÛË ÙˆÓ Ô˘‰ÂÙÂÚÔʛψÓ, ηıÒ˜ Î·È Ë ·ÂÏ¢ı¤ÚˆÛË ÙÔ˘ LTB4, ›Ûˆ˜ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ¯ÚfiÓÈ·˜ ·ÔÊÚ·ÎÙÈ΋˜ Ó¢ÌÔÓÔ¿ıÂÈ·˜, fiÔ˘ Ë ÙÔÈ΋ ÂÌÊ¿ÓÈÛË ÂÓfi˜ ¯ËÌÂÈÔÂÏÎÙÈÎÔ‡ Û‹Ì·ÙÔ˜ ÌÂÛÔÏ·‚› 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 ·fi ÙÔÓ Ù‡Ô ÙÔ˘ ΢ÙÙ¿ÚÔ˘ Ô˘ ÂÓÂÚÁÔÔÈ› (20). ™Â Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜, ÙÔ LTB4 ·Ú¿ÁÂÙ·È Î˘Ú›ˆ˜ ÛÙ· Ô˘‰ÂÙÂÚfiÊÈÏ·, ÂÓÒ Î·Ù¿ ÙË ÊÏÂÁÌÔÓ‹ Û˘ÓÙ›ıÂÙ·È Î·È Û ¿ÏÏÔ˘˜ Ù‡Ô˘˜ ΢ÙÙ¿ÚˆÓ Ô˘ ‰È·ı¤ÙÔ˘Ó ˘‰ÚÔÏ¿ÛË ÙÔ˘ LTA4 (22). ™Ù· ˈÛÈÓfiÊÈÏ· ÚÔ¿ÁÂÈ ÙË ¯ËÌÂÈÔÙ·Í›·, ÂÓÂÚÁÔÔÈ› ÙËÓ ÔÍÂȉ¿ÛË Ù˘ NADPH Î·È ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ MAP ÎÈÓ·ÛÒÓ. ÀÂÚ¤ÎÊÚ·ÛË ÙÔ˘ LTB4 ¤¯ÂÈ ·Ó·ÊÂÚı› ÛÙËÓ „ˆÚ›·ÛË (36), ÙÔ ‚ÚÔÁ¯ÈÎfi ¿ÛıÌ· (37), ÙË ÚÂ˘Ì·ÙÔÂȉ‹ ·ÚıÚ›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 ˘ÔÛÙËÚȯı› fiÙÈ ·˘Ùfi˜ Èı·ÓÒ˜ Û˘ÌÌÂÙ¤¯ÂÈ ÛÙË ‰È·‰Èηۛ· 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 ·ÙÔÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ, ÂÓÙÔ‡ÙÔȘ, ÙfiÛÔ Ë ·Ú·ÁˆÁ‹ ÙÔ˘˜ fiÛÔ Î·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΋˜ ÓfiÛÔ˘ (44), ·ÓÔ›ÁÔ˘Ó Ó¤Ô˘˜ ÔÚ›˙ÔÓÙ˜ ÁÈ· ÙË ÌÂϤÙË ÙÔ˘ ‚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·ÈÓÔÙ˘È΋ ¤ÎÊÚ·ÛË (45). ™‹ÌÂÚ·, Û¯ÂÙÈο ÌÂÁ¿ÏÔ˜ ·ÚÈıÌfi˜ Ê·ÚÌ·ÎÔÁÂÓˆÌÈÎÒÓ ÌÂÏÂÙÒÓ ÂÛÙÈ¿˙ÂÈ ÛÙËÓ Èı·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 ÔÛÔÛÙfi Ù˘ ÌÂÙ·‚ÏËÙfiÙËÙ·˜ ‰È·ÊfiÚˆÓ ·Ú·Ì¤ÙÚˆÓ ÔÊ›ÏÂÙ·È ÛÙË ÁÂÓÂÙÈ΋ ÔÈÎÈÏfiÙËÙ· Î·È ÙÔÓ ÔÏ˘ÌÔÚÊÈÛÌfi 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
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¤¯ÂÈ ·Ú·ÙËÚËı› Û Ó‡ÌÔÓ· ·ÙfiÌˆÓ Ì ¢·ÈÛıËÛ›· ÛÙËÓ ·ÛÈÚ›ÓË, ÂÓÒ Ë ·¿ÓÙËÛË ÛÙË ˙ÈÏ¢ÙfiÓË ¤¯ÂÈ Û˘Û¯ÂÙÈÛÙ› Ì ÙÔÓ ÂÓÙÔÈÛÌfi ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ 5-LO (46,48). ∏ 5-LO ¤¯ÂÈ È‰È·›ÙÂÚË ÛËÌ·Û›· ÛÙË Û‡ÓıÂÛË ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ Û ‰È¿ÊÔÚ· ·ÙÙ·Ú· Ô˘ ÂÌϤÎÔÓÙ·È ÛÙË ÊÏÂÁÌÔÓ‹, fiˆ˜ Ù· ˈÛÈÓfiÊÈÏ· Î·È Ù· ÛÈÙ¢ÙÈο ·ÙÙ·Ú· Î·È Ë Ú‡ıÌÈÛË ÙÔ˘ ÂÓ˙‡ÌÔ˘ ÙfiÛÔ ÛÂ Â›Â‰Ô ‰Ú·ÛÙËÚÈfiÙËÙ·˜, fiÛÔ Î·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˘ ˘ÔÎÈÓËÙ‹ ÙÔ˘ ÁÔÓȉ›Ô˘ (10). ∂›Û˘, ÙÔ ÁÔÓ›‰ÈÔ Ô˘ Έ‰ÈÎÔÔÈ› ÙË Û˘ÓıÂÙ¿ÛË ÙÔ˘ LTC4 ÂÓÙÔ›˙ÂÙ·È ÛÙÔ 5q35 Î·È Û˘Ó‰¤ÂÙ·È ÁÂÓÂÙÈο Ì ̛· ÂÚÈÔ¯‹ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 5 Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔÓ ·ÙÔÈÎfi Î·È ·ÛıÌ·ÙÈÎfi Ê·ÈÓfiÙ˘Ô (15). ¶·Ú¿ÏÏËÏ·, ‰È¿ÊÔÚÔÈ ÔÏ˘ÌÔÚÊÈÛÌÔ› Û ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ¤Ó˙˘Ì· Û‡ÓıÂÛ˘ ÙˆÓ LTs ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛÙ› Ì ÙÔ Ê·ÈÓfiÙ˘Ô ÙÔ˘ ¿ÛıÌ·ÙÔ˜ ·fi ·ÛÈÚ›ÓË (49). ∏ Û‡Ó‰ÂÛË 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˜ ¤¯ÂÈ Û˘Û¯ÂÙÈÛÙ› Ì ÙËÓ ÂÌÊ¿ÓÈÛË ·ÙÔÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ Û ÏËı˘ÛÌÔ‡˜ Ù˘ ªÂÁ¿Ï˘ µÚÂÙ·Ó›·˜ (50) Î·È Ù˘ 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 ÛÂ Â›Â‰Ô ˘Ô‰Ô¯¤ˆÓ, fiÛÔ Î·È ÛÙË Û‡ÓıÂÛË ÙˆÓ ÌÂÛÔÏ·‚ËÙÒÓ. ∏ ÂÙÂÚÔÁ¤ÓÂÈ· ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ‰ÈηÈÔÏÔÁ› 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˘Î¿ÛÙË, Ú·ÓÏÔ˘Î¿ÛÙË) Î·È ·Ó·ÛÙÔÏ›˜ Ù˘ Û‡ÓıÂÛ˘ ÙˆÓ LTs (˙ÈÏ¢ÙfiÓË), Û˘ÓÔÏÈο ·Ó·ÊÂÚfiÌÂÓÔÈ ˆ˜ ÙÚÔÔÔÈËÙ¤˜ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ, ¤¯Ô˘Ó ‚ÚÂÈ ÂÊ·ÚÌÔÁ‹ ÛÙËÓ ÎÏÈÓÈ΋. OÈ ÙÚÔÔÔÈËÙ¤˜ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ Â›Ó·È Ë ÈÔ ÚfiÛÊ·Ù· ÂÈÛ·¯ı›۷ ηÙËÁÔÚ›· ÂÓ·ÏÏ·ÎÙÈ΋˜ ‹ ÂÈÎÔ˘ÚÈ΋˜ ıÂڷ¢ÙÈ΋˜ ÚÔÛ¤ÁÁÈÛ˘ ÙˆÓ ÂÈÛÓÂfiÌÂÓˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ, 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 ·ÛÈÚ›Ó˘ (AIA, aspirin-induced asthma), ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÂÌÊ¿ÓÈÛË ‚ÚÔÁ¯fiÛ·ÛÌÔ˘ ÌÂÙ¿ ·fi Ï‹„Ë Û·ÏÈ΢ÏÈÎÒÓ Î·È ¿ÏÏˆÓ ÌË ÛÙÂÚÔÂȉÒÓ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ ·Ú·ÁfiÓÙˆÓ (57). ªÂٷ͇ ¿ÏψÓ, Ë
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¯ÚfiÓÈ· ÊÏÂÁÌÔÓ‹ ÛÙÔ ∞π∞ Û¯ÂÙ›˙ÂÙ·È Ì ٷ ·˘ÍË̤ӷ ›‰· ˈÛÈÓÔÊ›ÏˆÓ Î·È Û˘ÓıÂÙ¿Û˘ ÙÔ˘ LTC4, Ô˘ ÂÚȤ¯ÂÙ·È Û ·˘Ù¿ Ù· ·ÙÙ·Ú· (15,57). ÕÙÔÌ· ¢·›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·ÎfiÏÔ˘ı˘ ¢fi‰ˆÛ˘ Ù˘ Ô‰Ô‡ Ù˘ LO, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ‰È·Ù·Ú¿ÛÛÂÙ·È Ë ÈÛÔÚÚÔ›· ÌÂٷ͇ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ (PGE2) Î·È ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ (cysLTs) ÌÂÛÔÏ·‚ËÙÒÓ (57). º·ÚÌ·ÎÔÎÈÓËÙÈο, Ë ˙ÈÏ¢ÙfiÓË ·ÏÏËÏÂȉڿ Ì ÙË ıÂÔÊ˘ÏÏ›ÓË Î·È ¿ÏÏ· Ê¿Ú̷η Ô˘ ÌÂÙ·‚ÔÏ›˙ÔÓÙ·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˘Î¿ÛÙ˘ (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 ‰ÂÚÌ·Ù›Ùȉ· (60,61). ¶ÚÔηٷÚÎÙÈΤ˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ô˘ ·ÊÔÚÔ‡Ó ÛÙËÓ Âԯȷ΋ ·ÏÏÂÚÁÈ΋ ÚÈÓÔÂÈÂÊ˘Î›Ùȉ· ¤‰ÂÈÍ·Ó fiÙÈ Ë Û˘Á¯ÔÚ‹ÁËÛË ·ÓÙ·ÁˆÓÈÛÙÒÓ ÙˆÓ ∏1 Î·È cysLT1 ˘Ô‰Ô¯¤ˆÓ ‹Ù·Ó ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚË Ù˘ ÌÔÓoıÂڷ›·˜ (62). ∆¤ÏÔ˜, ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ó·ÊÔÚ¤˜ ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ Èı·Ó‹ ÂÈÛ·ÁˆÁ‹ ÛÙË ıÂڷ¢ÙÈ΋ ÓÂfiÙÂÚˆÓ Ô˘ÛÈÒÓ Ô˘ ‰ÚÔ˘Ó Û ‰È¿ÊÔÚ˜ Ê¿ÛÂȘ Ù˘ Û‡ÓıÂÛ˘ ÙˆÓ Ï¢ÎÔÙÚÈÂÓ›ˆÓ, ·ÏÏ¿ Î·È ÛÙÔ˘˜ ˘Ô‰Ô¯Â›˜ 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 ÂÎÏÂÎÙÈÎÒÓ ·Ú·ÁÒÁˆÓ ¤‰ˆÛ ÙȘ Ô˘Û›Â˜ SC56938 Î·È SC57461∞, ÔÈ Ôԛ˜ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ÂÎÏÂÎÙÈΤ˜ Î·È ·fi 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 Ë ZK158252 ¤¯ÂÈ ·ÓÙ·ÁˆÓÈÛÙÈ΋ ‰Ú¿ÛË ¤Ó·ÓÙÈ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ΢ÙÙ·ÚÔÏ·ÛÌ·ÙÈ΋˜ ÌÂÌ‚Ú¿Ó˘ Î·È ·ÁˆÓÈÛÙÈ΋ ¤Ó·ÓÙÈ ÙˆÓ ˘ÚËÓÈÎÒÓ, ÂÓÒ Ô ·ÓÙ·ÁˆÓÈÛÙ‹˜ 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 J Exp Physiol Cogn Med Sci 1940;30:121-145. 2. Brocklehurst WE. The release of histamine and formation of
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∏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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Paediatriki 2003;66:163-165
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¶ÚfiÁÚ·ÌÌ· ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘ ˘fi ÙËÓ ∂ÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›· ∆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›ÔÈ Û˘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 of European Specialists in Pediatrics (CESP), fiˆ˜ ·˘Ù¤˜ ‰È·ÌÔÚÊÒıËÎ·Ó ·fi ÙËÓ Committee for Continuing Medical 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˜ ÂΉËÏÒÛÂȘ 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˜ ‹ 150 ÌfiÚÈ· ̤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›ˆÓ Ô˘ ·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· ÈÛÙÔÔÈËÙÈο ·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¤‰ÚÈÔ 1 ÌfiÚÈÔ ·Ó¿ ÒÚ· ÁÈ· ÔÔÈ·‰‹ÔÙ ¿ÏÏË ÂΉ‹ÏˆÛË Ù˘ ∂.¶.∂. 2. ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ 8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË 3. µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ 8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË ¶·È‰Ô·ÏÏÂÚÁÈÔÏÔÁÈ΋ ∏ÌÂÚ›‰·: 6 ÌfiÚÈ· ¶·È‰Ô·ÏÏÂÚÁÈÔÏfiÁÔÈ Î·È ¶·È‰ÔÓ¢ÌÔÓÔÏfiÁÔÈ 3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ 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˘ ¶·ÙÚÒÓ 5 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË
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5 ÌfiÚÈ· ÙÔ ÎÏÈÓÈÎfi ÊÚÔÓÙÈÛÙ‹ÚÈÔ ·È‰ÈÎÔ‡ ¿ÛıÌ·ÙÔ˜ 9. ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ πˆ·ÓÓ›ÓˆÓ 8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË 10. ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘ 8 ÌfiÚÈ· ÙÔ ¶·ÁÎÚ‹ÙÈÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ™˘ÌfiÛÈÔ 11. ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·Ï›·˜ 5 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË 12. ¡ÂÔÁÓÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ £ÂÛÛ·ÏÔӛ΢ 4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË 13. ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¡ÔÛËÏ¢ÙÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ 4 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË 14. ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›· µÔÚ›Ԣ ∂ÏÏ¿‰Ô˜ 8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË 2 ÌfiÚÈ· Ë ªËÓÈ·›· ∂Ή‹ÏˆÛË ºÚÔÓÙÈÛÙ‹ÚÈÔ ∞Ó·˙ˆÔÁfiÓËÛ˘ ¡ÂÔÁÓÔ‡-µÚ¤ÊÔ˘˜-¶·È‰ÈÔ‡: 6 ÌfiÚÈ· ¡ÂÔÁÓÔÏfiÁÔÈ Î·È ∂ÓÙ·ÙÈÎÔÏfiÁÔÈ ¶·È‰›·ÙÚÔÈ 3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ 15. ¶·ÁÎÚ‹ÙÈ· ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›· 8 ÌfiÚÈ· Ë ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË 16. ∞ÈÌ·ÙÔÏÔÁÈ΋-OÁÎÔÏÔÁÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›· ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 8 ÌfiÚÈ· ¶·È‰Ô·ÈÌ·ÙÔÏfiÁÔÈ-¶·È‰ÔÔÁÎÔÏfiÁÔÈ 4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ 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 ˘ÔÂȉÈÎÔÙ‹ÙˆÓ 18. ¶·È‰ÔÓ¢ÚÔÏÔÁÈ΋ ∂Ù·ÈÚ›· ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 2 ÌfiÚÈ· ¶·È‰ÔÓ¢ÚÔÏfiÁÔÈ 1 ÌfiÚÈÔ °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ 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 ˘ÔÂȉÈÎÔÙ‹ÙˆÓ 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 ˘ÔÂȉÈÎÔÙ‹ÙˆÓ 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·ÛÙÚÂÓÙÂÚÔÏfiÁÔÈ 3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ ™˘ÌfiÛÈÔ: 5 ÌfiÚÈ· ¶·È‰ÔÁ·ÛÙÚÂÓÙÂÚÔÏfiÁÔÈ 3 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ 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
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¶·Ú¿ÚÙËÌ· £ÂÛÛ·Ï›·˜: 4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ¶·È‰È·ÙÚÈ΋˜ Î·È ∂ÊË‚È΋˜ ∂Ó‰ÔÎÚÈÓÔÏÔÁ›·˜ ∂Ù‹ÛÈ· ∂Ή‹ÏˆÛË: 4 ÌfiÚÈ· ¶·È‰ÔÂÓ‰ÔÎÚÈÓÔÏfiÁÔÈ 2 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ ∂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¢ÌÔÓÔÏfiÁÔÈ 5 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ ‚) 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˘˜ ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· §ÔÈÌÒÍÂˆÓ 5 ÌfiÚÈ· ™ÂÌÈÓ¿ÚÈÔ ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ¶ÂÚÈÁÂÓÓËÙÈ΋˜ π·ÙÚÈ΋˜ 8 ÌfiÚÈ· ¡ÂÔÁÓÔÏfiÁÔÈ 4 ÌfiÚÈ· °ÂÓÈÎÔ› ¶·È‰›·ÙÚÔÈ Î·È ¶·È‰›·ÙÚÔÈ ¿ÏÏˆÓ ˘ÔÂȉÈÎÔÙ‹ÙˆÓ ∫·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·ÚÌÔṲ̂ÓÔ˜ ÛÙËÓ ÂοÛÙÔÙ ÂÈÎÚ·ÙÔ‡Û· ηٿÛÙ·ÛË. O ¶Úfi‰ÚÔ˜ Ù˘ ∂ÏÏËÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ ∂Ù·ÈÚ›·˜
O ¶Úfi‰ÚÔ˜ Ù˘ ∂ÈÙÚÔ‹˜ ™˘Ó¯È˙fiÌÂÓ˘ ¶·È‰È·ÙÚÈ΋˜ ∂η›‰Â˘Û˘
∞Ó‰Ú¤·˜ °. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜
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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·ÈÚ›·. ¶·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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LETTER TO THE EDITOR
∫‡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 ÚÔÙÂÈÓfiÌÂÓÔ 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’ ·ӿÏË„ÈÓ ÂÏÏ›„ÂȘ, ÙȘ Ôԛ˜ Ù›ÓÂÈ Ó· Û˘ÌÏËÚÒÛÂÈ Ë ÂÙ·ÈÚ›· °ÂÚÔÏ˘Ì¿ÙÔ˘ Ì ÙÔ ÂÌ‚fiÏÈÔ POLYORAL. ∞ÚÎÂÙÔ› ÂÎ ÙˆÓ Û˘Ó·‰¤ÏÊˆÓ ÙÔ ¯ÚËÛÈÌÔÔÈÔ‡Ó, ·Ó Î·È ÙÔ Ï›ÛÙÔ ÙÔ ÂÌ‚ÔÏ›Ô˘ ·Ú·Ì¤ÓÂÈ ÚÔÛÚÔÊË̤ÓÔ 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 ÛÙË ÌÓ‹ÌË ÙˆÓ ÂÚÈÛÛfiÙÂÚˆÓ, ȉ›ˆ˜ ·Ï·ÈÒÓ ·È‰È¿ÙÚˆÓ, ˆ˜ Ì›· ÛÔ‚·Ú‹ ÓfiÛÔ˜, ı· ‹Ù·Ó ̷ο‚ÚÈÔ Ï¿ıÔ˜ Â¿Ó ÌÂÙ¿ ·fi ÙfiÛ· ÂÌ‚fiÏÈ· Ô˘ ‰È·ı¤ÙÔ˘Ì ۋÌÂÚ· Ì ÂÈfiÏ·È· Û˘ÌÂÚÈÊÔÚ¿ Î·È ¯ÂÈÚÈÛÌÔ‡˜, Û˘ÓÙÂϤÛÔ˘Ì ÒÛÙ ӷ ·ÓÂÌÊ·ÓÈÛÙ› ÛÙË ¯ÒÚ· Ì·˜ Ë ÔÏÈÔÌ˘ÂÏ›Ùȉ·, ÙÒÚ· Ô˘ ÛÙË ¯ÒÚ· Ì·˜ ˘¿Ú¯ÂÈ ¤Ó·˜ ÈηÓfi˜ ·ÎfiÌË ·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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