Παιδιατρική | Τόμος 69 • Τεύχος 4 • Ιούλιος - Αύγουστος 2006

¶·È‰È·ÙÚÈ΋ ∆fiÌÔ˜ 69 ñ ∆‡¯Ô˜ 4 ñ IÔ‡ÏÈÔ˜-∞‡ÁÔ˘ÛÙÔ˜ 2006 ¢ÈÌËÓÈ·›· ¤Î‰ÔÛË Ù˘ EÏÏËÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ EÙ·ÈÚ›·˜ ¶Úfi‰ÚÔ˜ ∞. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜ ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘ ∫. ™ÙÂÊ·Ó›‰Ë˜ M¤ÏË ¶. ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘ ∂. ∞ÓÙˆÓÔÔ‡ÏÔ˘ A. µ·˙·›Ô˘-°ÂÚ·ÛÈÌ›‰Ë °. µ·ÚÏ¿Ì˘ ª. ∫·Ó¿ÚÈÔ˘ ∂. ∫·ÙÛ·ÚÔ‡-¶ÂÎÙ·Û›‰Ë A. K·ÙÙ¿Ì˘ Ã. ∫ÒÛÙ·ÏÔ˜ ¡. ¶··‰fiÔ˘ÏÔ˜ ∞. ¶··‰ÔÔ‡ÏÔ˘ ∞. ™È·ÌÔÔ‡ÏÔ˘-ª·˘Ú›‰Ô˘ ª. ∆ÛÔÏÈ¿

¶ÂÚȯfiÌÂÓ· ∞¡∞™∫O¶∏™∂π™ 247 π·ÙÚÈ΋ ‚·ÛÈṲ̂ÓË ÛÙȘ ÂӉ›ÍÂȘ – ∆È ·ÏÏ¿˙ÂÈ ÛÙËÓ È·ÙÚÈ΋ Ú¿ÍË; ™. ∏Ï›·, µ. ∞ÁÁÂÏ¿ÎÔ˘ 255 °ÔÓ›‰È· Î·È Ì˯·ÓÈÛÌÔ› ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ ¶.¶. ¶¤ÙÚÔ˘ 268 √ÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ: ·›ÙÈ· Î·È ÚfiÏË„Ë ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ∫. ∫·ÏÔ‹Ù·, ∞. ∑¿ÚÚÔ˜, ∞. ∞ÓÙˆÓfiÔ˘ÏÔ˜, π.™. ¶··‰fiÔ˘ÏÔ˜

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ISSN 0377-2551

286 ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÊÔÚ¤ˆÓ Ù˘ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÂÈÓÂÊÚȉ›ˆÓ ÛÙËÓ ∂ÏÏ¿‰· Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÌÔÚÈ·ÎÒÓ Ù¯ÓÈÎÒÓ ∞. ¢·ÛÙ·Ì¿ÓË, ª. ¢Ú·ÎÔÔ‡ÏÔ˘, ∞. ™ÂÚÙ‰¿ÎË, °.¶. ÃÚÔ‡ÛÔ˜, ∞. ¢¿ÎÔ˘-µÔ˘ÙÂÙ¿ÎË 294 ÀÂÚ¿ÚÈıÌ· ¯ÚˆÌÔÛˆÌÈο ıÚ·‡ÛÌ·Ù· ÚÔÂÚ¯fiÌÂÓ· ·fi ÙÔ ¯ÚˆÌfiۈ̷ 15: Û˘Û¯¤ÙÈÛË Ê·ÈÓÔÙ‡Ô˘-ÁÔÓÔÙ‡Ô˘ ∞. ∫ÔÏȷϤÍË, ™. ∫›ÙÛÈÔ˘, Œ. ºÚ˘Û›Ú·, Ã. ™ÔÊÔÎÏ¤Ô˘˜, ∂. ∫Ô˘‚›‰Ë, ∫. ™·Ï·‚Ô‡Ú·, ∞. ª·‡ÚÔ˘ ¶∂ƒπ§∏æ∏ ∞¶√ ∆∏ µπµ§π√°ƒ∞ºπ∞ 300 Child abuse registration, fetal growth, and preterm birth: a population based study N. Spencer, A. Wallace, R. Sundrum, C. Bacchus, S. Logan

301 ™Ã√§π√ ∞¶√ ∆∏ ™À¡∆∞•∏ N. Spencer ∂¡¢π∞º∂ƒ√À™∂™ ¶∂ƒπ¶∆ø™∂π™ 302 ∞ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ Û¯ÂÙÈ˙fiÌÂÓÔ Ì ÙÔÓ Èfi Epstein-Barr. ¶ÂÚÈÁÚ·Ê‹ ‰‡Ô ÂÚÈÙÒÛÂˆÓ Ì ‰È·ÊÔÚÂÙÈ΋ ÎÏÈÓÈ΋ ¤Î‚·ÛË ∂. ¢ËÏ·Ó¿˜, µ. ¢·ÓËÏ¿ÙÔ˘, ∞. ∫·ÌÔ˘Ú¿Î˘, ∂.§. ª·ÚοÎË, ∂. ™ÙÂȷοÎË, ª. ∫·ÏÌ·ÓÙ‹ 310 √Í›· ·ÁÎÚ·ٛÙȉ· Û ·È‰› Ì Ïԛ̈ÍË ·fi Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ ¶. ¡ÂÔÓ¿ÎË, ™. ª¿Ú·Î·, ™. ™ÙÂÊ·Ó¿ÎË, ∞. ∆ÛÈÏÈÌÈÁοÎË 313 ∞˘¯ÂÓÈÎfi ÏÈÔ‚Ï¿Ûو̷ Û ‚Ú¤ÊÔ˜: Ì›· Û¿ÓÈ· ÎÏÈÓÈ΋ ÔÓÙfiÙËÙ· ∞. ∆Û·ÏΛ‰Ë˜, ™. °·Ú‰›Î˘, ∏. ∫·Ú·¿ÓÙ˙Ô˜, ∫. ∫·ÌÔ‡ÚË, ™. ¢Â˘ÙÂÚ·›Ô˜, ∞. °È·ÙÚÔ̷ӈϿÎË, ∂. ™È‚Ú›‰Ë˜, ∞. ÷Ù˙ËÌȯ·‹Ï ¶ƒ∞∫∆π∫O £∂ª∞ 317 ¡ÙfiÈÓÁÎ Û ·È‰È¿, ÂÊ‹‚Ô˘˜ Î·È Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ ™. ∞ÓÙˆÓÈ¿‰Ë˜ 323 ∫§π¡π∫√ ∫√Àπ∑ ¢. ™È·¤Ú·, ∞. ªËÙÛÈÒÓË, ∫. ™ÙÂÊ·Ó›‰Ë˜ 324 ¡∂∞ ∞¶√ ∆√ ¢π∞¢π∫∆À√ ¶·È‰È¿ Î·È ∆¤¯ÓË ¡. ¶··‰fiÔ˘ÏÔ˜

Paediatriki Volume 69 ñ Number 4 ñ July-August 2006 Bimonthly Publication of the Greek Paediatric Society President A. Constantopoulos Editorial Board Editor-in-Chief C. Stefanidis

Contents

Members P. Augoustides-Savvopoulou H. Antonopoulou A. Vazeou-Gerasimidi G. Varlamis M. Kanariou ∂. Katsarou-Pectasides A. Kattamis Ch. Costalos N. Papadopoulos ∞. Papadopoulou A. Siamopoulou-Mavridou M. Tsolia

REVIEW ARTICLES

Manuscript Editing

ORIGINAL ARTICLES

Greek Editing F. Mavroidi English Editing S. Nakou Publisher K. Griveas Publishing Coordinator SCIENTIFIC PUBLICATIONS Ltd 3 Artemidos str.

GR - 151 25, Maroussi Tel.: +30 210 87 78 810 Fax: +30 210 87 78 822 Owner Greek Paediatric Society© 92 Michalakopoulou str.

GR - 115 28, Athens Tel.: +30 210 7771 140 +30 210 7771 663 Fax: +30 210 7758 354 e-mail: hps@ath.forthnet.gr Annual Subscription All foreign countries: US $ 50

247 Evidence based medicine - What changes in clinical practice?

S. Ilia, V. Agelakou 255 Genes and mechanisms in kidney development P.P. Petrou 268 Domestic environment: causes and prevention of childhood accidents K. Kalopita, A. Zarros, A. Antonopoulos, J.S. Papadopoulos

278 Accidents in children 6-12 years old in Patras during the years 2000 and 2003 A. Alexopoulos, I. Detorakis, E. Detorakis, O. Pagonopoulou, G. Krokidas 286 Detection of congenital adrenal hyperplasia carrier frequency in Greece by molecular methods A. Dastamani, M. Dracopoulou, A. Sertedaki, G.P. Chroussos, A. Dakou-Voutetakis 294 Supernumerary marker chromosomes derived from chromosome 15: phenotype–genotype correlation A. Kolialexi, S. Kitsiou, H. Fryssira, C. Sofocleous, E. Kouvidi, K. Salavoura, A. Mavrou

301 EDITORIAL COMMENTARY N. Spencer CASE REPORTS 302 Haemophagocytic syndrome related to Epstein-Barr virus. Report of two cases with different clinical outcome E. Dilanas, V. Danilatou, A. Kambourakis, E.-A. Markaki, E. Stiakaki, M. Kalmanti 310 Acute pancreatitis in a child with pneumonia due to Mycoplasma pneumoniae P. Neonaki, S. Maraka, S. Stefanaki, A. Tsilimigaki 313 Posterior cervical lipoblastoma: a rare neck mass in childhood A. Tsalkidis, S. Gardikis, E. Karapantzos, K. Kabouri, S. Deftereos, A. Giatromanolaki, E. Sibridis, A. Chatzimichael PRACTICAL ISSUE 317 Doping in children, adolescents and young adults S. Antoniadis 323 CLINICAL QUIZ D. Siapera, A. Mitsioni, C. Stefanidis 324 NEWS FROM THE INTERNET

ABSTRACT 300 Child abuse registration, fetal growth, and preterm birth: a population based study N. Spencer, A. Wallace, R. Sundrum, C. Bacchus, S. Logan

Children and Art N. Papadopoulos

™À¡∆∞∫∆π∫∏ E¶π∆ƒ√¶∏

EDITORIAL BOARD

¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘

Editor-in-Chief

∫ˆÓÛÙ·ÓÙ›ÓÔ˜ ™ÙÂÊ·Ó›‰Ë˜, ∞ı‹Ó·

Constantinos Stefanidis, Athens

À‡ı˘ÓÔÈ ™‡ÓÙ·Í˘ ∂ÍÂȉÈ·ۈÓ

Section Editors

∂ϤÓË ∞ÓÙˆÓÔÔ‡ÏÔ˘, ∞ı‹Ó· ∞Ó·Ù˘ÍȷΤ˜ ‰È·Ù·Ú·¯¤˜ - ¶ÚÔ‚Ï‹Ì·Ù· Û˘ÌÂÚÈÊÔÚ¿˜

Eleni Antonopoulou, Athens Developmental and behavioral pediatrics

¶ÂÚÛÂÊfiÓË ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘, £ÂÛÛ·ÏÔÓ›ÎË KÏËÚÔÓÔÌÈο ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·

Persephone Augoustides-Savvopoulou, Thessaloniki Inborn Errors of Metabolism

∞Ó‰ÚÈ·Ó‹ µ·˙·›Ô˘-°ÂÚ·ÛÈÌ›‰Ë, ∞ı‹Ó· ∂Ó‰ÔÎÚÈÓÔÏÔÁ›·

Andriani Vazaiou-Gerasimidi, Athens Endocrinology

°ÂÒÚÁÈÔ˜ µ·ÚÏ¿Ì˘, £ÂÛÛ·ÏÔÓ›ÎË ∫·Ú‰ÈÔÏÔÁ›·

George Varlamis, Thessaloniki Cardiology

ª·Ú›· ∫·Ó¿ÚÈÔ˘, ∞ı‹Ó· ∞ÓÔÛÔÏÔÁ›·

Maria Kanariou, Athens Immunology

∂˘ÛÙ·ı›· ∫·ÙÛ·ÚÔ‡-¶ÂÎÙ·Û›‰Ë, ∞ı‹Ó· ¡Â˘ÚÔÏÔÁ›·

Eustathia Katsarou-Pektasidou, Athens Neurology

∞ÓÙÒÓ˘ ∫·ÙÙ¿Ì˘, ∞ı‹Ó· ∞ÈÌ·ÙÔÏÔÁ›· - OÁÎÔÏÔÁ›·

Antonis Kattamis, Athens Haematology - √ncology

ÃÚ‹ÛÙÔ˜ ∫ÒÛÙ·ÏÔ˜, ∞ı‹Ó· ¡ÂÔÁÓÔÏÔÁ›·

Christos Kostalos, Athens Neonatology

∞ÏÂÍ¿Ó‰Ú· ¶··‰ÔÔ‡ÏÔ˘, ∞ı‹Ó· °·ÛÙÚÂÓÙÂÚÔÏÔÁ›· - ∏·ÙÔÏÔÁ›· - ¢È·ÙÚÔÊ‹

Alexandra Papadopoulou, Athens Gastroenterology - Hepatology - Nutrition

¡ÈÎfiÏ·Ô˜ ¶··‰fiÔ˘ÏÔ˜, ∞ı‹Ó· ∞ÏÏÂÚÁÈÔÏÔÁ›· - ¶Ó¢ÌÔÓÔÏÔÁ›·

Nicos Papadopoulos, Athens Allergology - Pneumonology

∞ÓÙÈÁfiÓË ™È·ÌÔÔ‡ÏÔ˘-ª·˘Ú›‰Ô˘, πˆ¿ÓÓÈÓ· ƒÂ˘Ì·ÙÔÏÔÁ›·

Antigoni Siamopoulou-Mavridou, Ioannina Rheumatology

ª·Ú›˙· ∆ÛÔÏÈ¿, ∞ı‹Ó· §ÔÈ̈ÍÈÔÏÔÁ›·

Marisa Tsolia, Athens Infectious Diseases

ª¤ÏË Ù˘ ¢ÈÂıÓÔ‡˜ ™˘ÓÙ·ÎÙÈ΋˜ ∂ÈÙÚÔ‹˜ ñ Members of the International Editorial Board Alexis Arzimanoglou, Paris, France

Christer Holmberg, Helsinki, Finland

Ellis D. Avner, Milwaukee, USA

Peter Hoyer, Essen, Germany

Swati Bhave, New Delhi, India

Jan Janda, Prague, Czech Republic

Alberto Bissot, Panama, Panama

Jan Kimpen, Ultrecht, Netherlands

David Branski, Jerusalem, Israel

John Manis, Boston, USA

Francesco Chiarelli, Chieti, Italy

Manuel Moya, Alicante, Spain

Chok-Wan Chan, Hong Kong, China

Hugh O'Brodovich, Toronto, Canada

Denis Daneman, Toronto, Canada

Ross Petty, Vancouver, Canada

Jochen Ehrich, Hannover, Germany

Willem Proesmans, Leuven, Belgium

Demetrius Ellis, Pittsburgh, USA

Jose Ramet, Antwerp, Belgium

Yoshikatsu Eto, Tokyo, Japan

Alan Sinaiko, Minneapolis, USA

Richard N. Fine, Stony Brook, USA

Nick J. Spencer, Coventry, UK

Margaret C. Fisher, Philadelphia, USA

Alfred Tenore, Udine, Italy

Raif Geha, Boston, USA

Alkis Togias, Bethesda, USA

Adenike Grange, Lagos, Nigeria

Eva Tsalikian, Iowa City, USA

Judith G. Hall, Vancouver, Canada

Catherine Weil-Olivier, Paris, France

Patricia Hamilton, London, UK

Johannes Zschocke, Heidelberg, Germany

Enver Hasanoglu, Ankara, Turkey

v

√¢∏°π∂™ ¶ƒ√™ ∆√À™ ™À°°ƒ∞º∂π™ A. °ÂÓÈΤ˜ ¶ÏËÚÔÊÔڛ˜ ∆Ô ÂÚÈÔ‰ÈÎfi “¶·È‰È·ÙÚÈ΋” Â›Ó·È Ë ÂÈÛÙËÌÔÓÈ΋ ¤Î‰ÔÛË Î·È È‰ÈÔÎÙËÛ›· Ù˘ EÏÏËÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ EÙ·ÈÚ›·˜, Ô˘ ‰È·Ó¤ÌÂÙ·È ÛÙ· ̤ÏË Ù˘. Œ¯ÂÈ ˆ˜ ‚·ÛÈÎÔ‡˜ ÛÙfi¯Ô˘˜ ÙËÓ ·ÔÙ‡ˆÛË ÙÔ˘ ·È‰È·ÙÚÈÎÔ‡ ÂÈÛÙËÌÔÓÈÎÔ‡ ¤ÚÁÔ˘ Î·È ÙË Û˘Ó¯‹ ÂÓË̤ڈÛË ÙˆÓ ¶·È‰È¿ÙÚˆÓ. °È· ÙÔ ÛÎÔfi ·˘Ùfi ‰¤¯ÂÙ·È ÁÈ· ‰ËÌÔÛ›Â˘ÛË ÔÈÎÈÏ›· ¿ÚıÚˆÓ Î·È Û˘ÁÎÂÎÚÈ̤ӷ: 1. ÕÚıÚ· Û‡ÓÙ·Í˘ (ÌÂÙ¿ ·fi ÚfiÛÎÏËÛË Ù˘ ™˘ÓÙ·ÎÙÈ΋˜ EÈÙÚÔ‹˜).

2. ∞Ó·ÛÎÔ‹ÛÂȘ.

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7. ∂›Î·ÈÚ· ı¤Ì·Ù·.

8. £¤Ì·Ù· ÂÎ·›‰Â˘Û˘ Î·È ÔÚÁ¿ÓˆÛ˘ ˘Á›·˜.

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10. ™‡ÓÙÔÌ· Ó¤·.

11. µÚ·¯Â›Â˜ ‰ËÌÔÛȇÛÂȘ.

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13. ¶ÂÚÈÏ‹„ÂȘ Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜.

14. ∞Ó·ÎÔÈÓÒÛÂȘ ÚÔÛ¯ÒÓ Û˘Ó‰ڛˆÓ Î·È ÂÈÛÙËÌÔÓÈÎÒÓ ÂΉËÏÒÛÂˆÓ 15. ∞Ó·ÊÔÚ¤˜ Î·È ÎÚÈÙÈ΋ Ó¤ˆÓ ÂΉfiÛˆÓ, ÂÏÏËÓÈÎÒÓ Î·È Í¤ÓˆÓ, ·È‰È·ÙÚÈÎÔ‡ ÂӉȷʤÚÔÓÙÔ˜.

H ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ‰È·ÙËÚ› ÙÔ ‰Èη›ˆÌ· Ó· ‰ËÌÔÛȇÂÈ ¿ÚıÚ· Ì ȉȷ›ÙÂÚÔ ÂÈÛÙËÌÔÓÈÎfi ÂӉȷʤÚÔÓ, ηıÒ˜ Î·È ¿ÚıÚ· Ì Â›Î·ÈÚ· ı¤Ì·Ù· ¯ˆÚ›˜ Ó· ÙËÚÂ›Ù·È Ë ÛÂÈÚ¿ ˘Ô‚ÔÏ‹˜. ∂›Û˘, ÌÔÚ› Ó· ·ÔÊ·Û›˙ÂÈ ÁÈ· ÙË ‰ËÌÔÛ›Â˘ÛË ÂÚÁ·ÛÈÒÓ Ô˘ ¤¯Ô˘Ó ·ÚÔ˘ÛÈ·ÛÙ› ÛÙÔ ÂÙ‹ÛÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ, ÙËÓ ÔÏÈ΋ ‹ ÌÂÚÈ΋ ‰ËÌÔÛ›Â˘ÛË ·ÚÔ˘ÛÈ¿ÛÂˆÓ È‰È·›ÙÂÚÔ˘ ÂӉȷʤÚÔÓÙÔ˜ Î·È ÙËÓ ÔÏÈ΋ ‹ ÌÂÚÈ΋ ‰ËÌÔÛ›Â˘ÛË ÂÈÛÙÔÏÒÓ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ‰ËÌÔÛÈÂ˘Ì¤Ó· ÂÈÛÙËÌÔÓÈο ¿ÚıÚ· ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. ™ÙȘ ÂÚÁ·Û›Â˜ Ì Â›Î·ÈÚ· ı¤Ì·Ù· Ú¤ÂÈ Ó· ·Ó·ÁÚ¿ÊÂÙ·È ÛÙËÓ ÚÒÙË ÛÂÏ›‰· Ë ÚfiıÂÛË ÙˆÓ Û˘ÁÁڷʤˆÓ ÁÈ· ÙËÓ ·Ó·ÁηÈfiÙËÙ· Ù˘ Ù·¯Â›·˜ ‰ËÌÔÛ›Â˘Û˘. ∏ ∂ÈÙÚÔ‹ ™‡ÓÙ·Í˘ ‰È·ÙËÚ› ÙÔ ‰Èη›ˆÌ· Ù˘ ·Ô‰Ô¯‹˜ Ù˘ Ù·¯Â›·˜ ‰ËÌÔÛ›Â˘Û˘. ŸÏ˜ ÔÈ ÂÚÁ·Û›Â˜ Ú¤ÂÈ Ó· ÌËÓ ¤¯Ô˘Ó ÂÓ Ì¤ÚÂÈ ‹ ÂÍ ÔÏÔÎÏ‹ÚÔ˘ ‰ËÌÔÛÈ¢ı› ‹ ˘Ô‚ÏËı› ÁÈ· ÎÚ›ÛË Û ¿ÏÏÔ ÂÚÈÔ‰ÈÎfi. ∂ÈϤÔÓ, ÛÙËÓ ÂÚÁ·Û›· ı· Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È Ù˘¯fiÓ ÂȉÔÙ‹ÛÂȘ-¯ÔÚËÁ›Â˜ ‹ ¿ÏϘ ËÁ¤˜ ˘ÔÛÙ‹ÚÈ͢. ŸÏ˜ ÔÈ ÎÏÈÓÈΤ˜ ¤Ú¢Ó˜ Ú¤ÂÈ Ó· ¤¯Ô˘Ó Á›ÓÂÈ ÌÂÙ¿ ·fi ÏËÚÔÊÔÚË̤ÓË Û˘Ó·›ÓÂÛË ÙˆÓ ÌÂÙ¯fiÓÙˆÓ ‹ ÙˆÓ ÓÔÌ›ÌˆÓ ÂÎÚÔÛÒˆÓ ÙÔ˘˜, Û‡Ìʈӷ Ì ÙȘ ‰È·ÎËÚ‡ÍÂȘ ÙÔ˘ EÏÛ›ÓÎÈ Î·È ÙÔ˘ TfiÎÈÔ. E›Û˘, Ú¤ÂÈ Ó· ¤¯Ô˘Ó ÙËÚËı› ÔÈ Ô‰ËÁ›Â˜ ÁÈ· ÙË ÊÚÔÓÙ›‰· ÂÈÚ·Ì·Ùfi˙ˆˆÓ ÙÔ˘ ∂ıÓÈÎÔ‡ πÓÛÙÈÙÔ‡ÙÔ˘ ÀÁ›·˜ ÙˆÓ ∏¶∞ (DHEW Publication, NIH, 80-23). OÈ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ú¤ÂÈ Ó· ¤¯Ô˘Ó ÂÁÎÚÈı› ·fi ÙËÓ ÂÈÙÚÔ‹ ∏ıÈ΋˜ Î·È ¢ÂÔÓÙÔÏÔÁ›·˜ ÙÔ˘ ¡ÔÛÔÎÔÌ›Ԣ.

OÈ ·fi„ÂȘ Î·È Ù· Û˘ÌÂÚ¿ÛÌ·Ù· ÙˆÓ Û˘ÁÁڷʤˆÓ Ô˘ ‰È·Ù˘ÒÓÔÓÙ·È ÛÙȘ ‰ËÌÔÛÈÂ˘Ì¤Ó˜ ÂÚÁ·Û›Â˜ ‰ÂÓ ·ÓÙÈηÙÔÙÚ›˙Ô˘Ó ··Ú·›ÙËÙ· ·˘Ù¤˜ ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. H ηٷ¯ÒÚÈÛË ‰È·ÊËÌ›ÛÂˆÓ ÛÙÔ ÂÚÈÔ‰ÈÎfi ‰ÂÓ ˘Ô‰ËÏÒÓÂÈ ÔˆÛ‰‹ÔÙ ¤ÁÎÚÈÛË ÙˆÓ ÂÚȯÔÌ¤ÓˆÓ ÙÔ˘˜ ·fi ÙËÓ EÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ EÙ·ÈÚ›·, ÙË ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ‹ ·fi ÙÔÓ EΉfiÙË ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. ŸÏ˜ ÔÈ ‰ËÌÔÛÈÂ˘Ì¤Ó˜ ÂÚÁ·Û›Â˜ ıˆÚÔ‡ÓÙ·È È‰ÈÔÎÙËÛ›· ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡ “¶·È‰È·ÙÚÈ΋” Î·È Ë ÔÏÈ΋ ‹ ÌÂÚÈ΋

xv

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

µ. ™‡ÓÙ·ÍË ÙˆÓ ∂ÚÁ·ÛÈÒÓ ŸÏ˜ ÔÈ ÂÚÁ·Û›Â˜ Ú¤ÂÈ Ó· ·ÎÔÏÔ˘ıÔ‡Ó “∫ÔÈÓ¤˜ ¶ÚԉȷÁڷʤ˜ ÁÈ· ÃÂÈÚfiÁÚ·Ê· Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û µÈÔ˚·ÙÚÈο ¶ÂÚÈÔ‰Èο” (Uniform Requirements for Manuscripts Submitted to Biomedical Journals), ÔÈ Ôԛ˜ ÙÚÔÔÔÈ‹ıËÎ·Ó ÚfiÛÊ·Ù· Î·È ‰ËÌÔÛȇÔÓÙ·È ÛÙȘ ‰È¢ı‡ÓÛÂȘ: http://www.icmje.org Î·È http://www.icmje.org/icmje.pdf TÔ Û‡ÓÔÏÔ Ù˘ ÂÚÁ·Û›·˜ (Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙˆÓ ÈÓ¿ÎˆÓ Î·È ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ ÂÈÎfiÓˆÓ) Ú¤ÂÈ Ó· Â›Ó·È Ù˘ˆÌ¤ÓÔ ÛÙË ÌÈ· fi„Ë Ï¢ÎÔ‡ ¯·ÚÙÈÔ‡ ÌÂÁ¤ıÔ˘˜ A4 (21x29,7 cm), Ì ‰ÈÏfi ‰È¿ÛÙËÌ· ÌÂٷ͇ ÙˆÓ ÁÚ·ÌÌÒÓ Î·È ÂÚÈıÒÚÈ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 2,5 cm ÛÙȘ ‰‡Ô Ï¢ڤ˜.

TÔ Î›ÌÂÓÔ Ú¤ÂÈ Ó· ¤¯ÂÈ ÙËÓ ·ÎfiÏÔ˘ıË ‰È¿Ù·ÍË: ÛÂÏ›‰· Ù›ÙÏÔ˘, ‚Ú·¯‡˜ Ù›ÙÏÔ˜, ÂÚ›ÏË„Ë ÛÙ· ÂÏÏËÓÈο Î·È Ù· ·ÁÁÏÈο, ηٿÏÔÁÔ˜ Û˘ÓÙÔÌÔÁÚ·ÊÈÒÓ, ΛÌÂÓÔ, ¢¯·ÚÈÛٛ˜ ηıÒ˜ Î·È ·Ó·ÊÔÚ¿ Û ÂȉÔÙ‹ÛÂȘ-¯ÔÚËÁ›Â˜ ‹ ¿ÏϘ ËÁ¤˜ ˘ÔÛÙ‹ÚÈ͢, ‚È‚ÏÈÔÁÚ·Ê›·, ›Ó·Î˜, ÂÈÎfiÓ˜, Ù›ÙÏÔÈ ÂÈÎfiÓˆÓ. K¿ı ¤Ó· ·fi Ù· ·Ú·¿Óˆ ÛÙÔȯ›· Ú¤ÂÈ Ó· ·Ú¯›˙ÂÈ Û ¯ˆÚÈÛÙfi ʇÏÏÔ Î·È ÔÈ ÛÂÏ›‰Â˜ Ó· ·ÚÈıÌÔ‡ÓÙ·È ‰È·‰Ô¯Èο ·Ú¯›˙ÔÓÙ·˜ Ì ÙË ÛÂÏ›‰· Ù›ÙÏÔ˘.

H ¤ÎÙ·ÛË ÚÔÛ‰ÈÔÚ›˙ÂÙ·È ÁÈ·: ñ ÙȘ ·Ó·ÛÎÔ‹ÛÂȘ Û 2000-3000 ϤÍÂȘ. ñ ÙȘ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜ Û 1500-2500 ϤÍÂȘ Î·È ÙȘ ÂӉȷʤÚÔ˘Û˜ ÂÚÈÙÒÛÂȘ Û 1000-1500 ϤÍÂȘ. ñ ÙȘ ‚Ú·¯Â›Â˜ ‰ËÌÔÛȇÛÂȘ Û 1000-1500 ϤÍÂȘ. ñ ÙȘ ÂÈÛÙÔϤ˜ Û 250-500 ϤÍÂȘ.

™ÂÏ›‰· Ù›ÙÏÔ˘ ¶Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ: ñ ÙÔÓ Ù›ÙÏÔ (<14 ϤÍÂȘ), ηıÒ˜ Î·È ÙÔÓ ‚Ú·¯‡ Ù›ÙÏÔ (<5 ϤÍÂȘ) ÙÔ˘ ¿ÚıÚÔ˘. ¢ÂÓ ÂÈÙÚ¤ÔÓÙ·È Û˘ÓÙÌ‹ÛÂȘ. ñ ÙÔ fiÓÔÌ· Î·È ÙÔ ÂÒÓ˘ÌÔ Î¿ıÂ Û˘ÁÁڷʤ· ÛÙËÓ ÔÓÔÌ·ÛÙÈ΋. ñ ÙÔ ÂÈÛÙËÌÔÓÈÎfi ΤÓÙÚÔ (›‰Ú˘Ì·, ÎÏÈÓÈ΋, ÂÚÁ·ÛÙ‹ÚÈÔ) ·fi fiÔ˘ ÚÔ¤Ú¯ÂÙ·È Ë ÂÚÁ·Û›·. ™Â ÂÚ›ÙˆÛË ¤ÏÏÂȄ˘ Û˘ÓÂÚÁ·Û›·˜ ÌÂ Û˘ÁÎÂÎÚÈ̤ӷ ΤÓÙÚ·, Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÂÙ·È Ë È‰ÈfiÙËÙ· ÙÔ˘/ÙˆÓ Û˘ÁÁڷʤ·/ˆÓ (.¯. ȉÈÒÙ˘ ·È‰›·ÙÚÔ˜) Î·È Ô ÙfiÔ˜ ‰È·ÌÔÓ‹˜ ÙÔ˘/ÙÔ˘˜. ñ ÙËÓ Ï‹ÚË ‰È‡ı˘ÓÛË, e-mail Î·È ÙÔ ÙËϤʈÓÔ ÙÔ˘ Û˘ÁÁڷʤ· Ì ÙÔÓ ÔÔ›Ô Á›ÓÂÙ·È Ë ·ÏÏËÏÔÁÚ·Ê›·.

¶ÂÚÈÏ‹„ÂȘ H ÂÚ›ÏË„Ë Ú¤ÂÈ Ó· ·Ó·ÎÂÊ·Ï·ÈÒÓÂÈ ÙÔ˘˜ ÛÙfi¯Ô˘˜ Ù˘ ÂÚÁ·Û›·˜, ÙË ÌÂıÔ‰ÔÏÔÁ›·, Ù· ΢ÚÈfiÙÂÚ· ·ÔÙÂϤÛÌ·Ù· Î·È Ù· Û˘ÌÂÚ¿ÛÌ·Ù· Ù˘ ÌÂϤÙ˘. ñ £· Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ˘Ï¿¯ÈÛÙÔÓ 200 ϤÍÂȘ, fï˜ ‰ÂÓ ı· Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙȘ 250 ϤÍÂȘ. ñ ∏ ÂÚ›ÏË„Ë ÙˆÓ ÂÚÁ·ÛÈÒÓ Ú¤ÂÈ Ó· Â›Ó·È ‰ÔÌË̤ÓË ÛÙȘ ÂÍ‹˜ ·Ú·ÁÚ¿ÊÔ˘˜: ÂÈÛ·ÁˆÁ‹, ̤ıÔ‰ÔÈ, ·ÔÙÂϤÛÌ·Ù· Î·È Û˘ÌÂÚ¿ÛÌ·Ù·. ™ÙËÓ ÂÚ›ÏË„Ë ÛÙ· ·ÁÁÏÈο Ú¤ÂÈ Ó· ·Ó·ÁÚ¿ÊÔÓÙ·È ÛÙËÓ ·Ú¯‹ ÙÔ˘ ÎÂÈ̤ÓÔ˘ Ô Ù›ÙÏÔ˜ Ù˘ ÂÚÁ·Û›·˜ Î·È Ù· ÔÓfiÌ·Ù· ÙˆÓ Û˘ÁÁڷʤˆÓ ÛÙ· ·ÁÁÏÈο. TÔ ÂÚȯfiÌÂÓÔ ÙÔ˘ ·ÁÁÏÈÎÔ‡ ÎÂÈ̤ÓÔ˘ Ú¤ÂÈ Ó· Â›Ó·È ‰ÔÌË̤ÓÔ ÛÂ: ÂÈÛ·ÁˆÁ‹ (background), ̤ıÔ‰ÔÈ (methods), ·ÔÙÂϤÛÌ·Ù· (results) Î·È Û˘ÌÂÚ¿ÛÌ·Ù· (conclusions). H ÂÚ›ÏË„Ë ÛÙ· ·ÁÁÏÈο ‰ÂÓ Ú¤ÂÈ Ó· ‰È·Ê¤ÚÂÈ ·fi ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÛÙ· ÂÏÏËÓÈο.

xvi

K¿Ùˆ ·fi ÙËÓ ÂÏÏËÓÈ΋ Î·È ÙËÓ ·ÁÁÏÈ΋ ÂÚ›ÏË„Ë ÛËÌÂÈÒÓÔÓÙ·È ÙÚÂȘ ¤ˆ˜ ¤ÓÙ ϤÍÂȘ ÎÏÂȉȿ Ô˘ ı· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÁÈ· ÙÔ ıÂÌ·ÙÈÎfi ¢ÚÂÙ‹ÚÈÔ.

K›ÌÂÓÔ OÈ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó: ÂÈÛ·ÁˆÁ‹, ÌÂıfi‰Ô˘˜, ·ÔÙÂϤÛÌ·Ù· Î·È Û˘˙‹ÙËÛË. H ÂÈÛ·ÁˆÁ‹ ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· ÙÂÏÂ˘Ù·›· ‰Â‰Ô̤ӷ Ù˘ ¤Ú¢ӷ˜ ÛÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ı¤Ì· Ì ÙȘ ΢ÚÈfiÙÂÚ˜ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·ÔÌ¤˜ Î·È ÙÔÓ ÛÎÔfi Ù˘ ÂÚÁ·Û›·˜. H ÂÚÈÁÚ·Ê‹ ÙˆÓ ÌÂıfi‰ˆÓ Ú¤ÂÈ Ó· Â›Ó·È ·ÎÚÈ‚‹˜ Î·È ·ÚÎÂÙ¿ ÏÂÙÔÌÂÚ‹˜, ÒÛÙ ӷ ÂÈÙÚ¤ÂÈ ÙËÓ ·Ó··Ú·ÁˆÁ‹ ÙÔ˘˜ ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜. ∂›Û˘, Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È Ì ÏÂÙÔ̤ÚÂȘ ÔÈ ÛÙ·ÙÈÛÙÈΤ˜ ̤ıÔ‰ÔÈ ·Ó¿Ï˘Û˘ Î·È ·ÍÈÔÏfiÁËÛ˘ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ. T· ·ÔÙÂϤÛÌ·Ù· Ú¤ÂÈ Ó· ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ì ۷ʋÓÂÈ· Î·È Ó· Û˘Óԉ‡ÔÓÙ·È ·fi ÙËÓ ··Ú·›ÙËÙË ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË. H Û˘˙‹ÙËÛË Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· Û˘ÌÂÚ¿ÛÌ·Ù· Ô˘ ÚÔ·ÙÔ˘Ó ·fi ÙËÓ ÂÚÁ·Û›·, ÙË ÛËÌ·Û›· Ô˘ ÌÔÚ› Ó· ¤¯Ô˘Ó Î·È ÙËÓ Èı·Ó‹ Û˘Û¯¤ÙÈÛ‹ ÙÔ˘˜ Ì ·Ú·ÙËÚ‹ÛÂȘ ¿ÏÏˆÓ ÂÚ¢ÓËÙÒÓ.

OÈ ÂӉȷʤÚÔ˘Û˜ ÂÚÈÙÒÛÂȘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Û‡ÓÙÔÌË ÂÈÛ·ÁˆÁ‹, ÂÚÈÁÚ·Ê‹ Ù˘ ÂÚ›ÙˆÛ˘ Î·È ‚Ú·¯Â›· Û˘˙‹ÙËÛË, Ì ¤ÌÊ·ÛË ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË.

T· ˘fiÏÔÈ· ı¤Ì·Ù· ¤¯Ô˘Ó ÂχıÂÚË ‰ÔÌ‹ ηٿ ÙËÓ ÎÚ›ÛË ÙˆÓ Û˘ÁÁڷʤˆÓ ÙÔ˘˜. ∂˘¯·ÚÈÛٛ˜ ‹ ·Ó·ÁÓˆÚ›ÛÂȘ (·Ó·ÊÔÚ¿ Û ÂȉÔÙ‹ÛÂȘ-¯ÔÚËÁ›Â˜ ‹ ¿ÏϘ ËÁ¤˜ ˘ÔÛÙ‹ÚÈ͢) ı· Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ Ù¤ÏÔ˜ ÙÔ˘ ÎÂÈ̤ÓÔ˘ Î·È ÚÈÓ ·fi ÙȘ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·ÔÌ¤˜.

Editors/ Uniform Requirements for Manuscripts Sub-mitted to Biomedical Journals, (http://www.icmje.org Î·È http:// www.icmje.org/icmje.pdf). OÈ Û˘ÓÙÌ‹ÛÂȘ ÙˆÓ Ù›ÙÏˆÓ ÙˆÓ ÂÚÈÔ‰ÈÎÒÓ Á›ÓÔÓÙ·È Ì ‚¿ÛË ÙÔ Cumulated Index Medicus [List of Journals Indexed in Index Medicus (http://www.nlm.nih.gov/bsd/uniform_requirements.html)]. ¶·Ú·‰Â›ÁÌ·Ù· ‚È‚ÏÈÔÁÚ·ÊÈÎÒÓ ·Ú·ÔÌÒÓ I. ¶∂ƒπO¢π∫∞ AÓ ÔÈ Û˘ÁÁÚ·Ê›˜ Â›Ó·È ¤ˆ˜ ¤ÍÈ, ·Ó·ÁÚ¿ÊÔÓÙ·È fiÏÔÈ, ÂÓÒ ·Ó Â›Ó·È ÂÙ¿ ‹ ÂÚÈÛÛfiÙÂÚÔÈ, ·Ó·ÁÚ¿ÊÔÓÙ·È ÔÈ ÚÒÙÔÈ ¤ÍÈ Î·È ÚÔÛÙ›ıÂÙ·È “et al” ‹ “Î·È Û˘Ó”.

T·ÎÙÈ΋ ¤Î‰ÔÛË ÂÚÈÔ‰ÈÎÔ‡: ∞ÓÙˆÓ›Ô˘ ¢, ª¿Ú· Ã, °È·ÓÓ¿ÙÔ˘ Ã. ∂Ì‚fiÏÈ·: Â›‰Ú·ÛË ÛÙËÓ ÂȉËÌÈÔÏÔÁ›· ÙˆÓ ÏÔÈ̈‰ÒÓ ÓÔÛËÌ¿ÙˆÓ Î·È ÙËÓ ·È‰È·ÙÚÈ΋ Ú¿ÍË. ¶·È‰È·ÙÚÈ΋ 1999;59:272-279.

Proesmans W. Bartter syndrome and its neonatal variant. Eur J Pediatr 1997;156:669-679. ™˘ÌÏËڈ̷ÙÈÎfi Ù‡¯Ô˜ ÂÚÈÔ‰ÈÎÔ‡: Flyvbjerg A. Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in the renal complications of diabetes. Kidney Int 1997;52 (60 Suppl):S12-S19. Èڛ˜ Û˘ÁÁڷʤ·: National Institutes of Health Consensus Development Conference. Neurofibromatosis conference statement. Arch Neurol 1988;45:575-578.

TÈ̤˜ ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛÂˆÓ OÈ ÙÈ̤˜ ÙˆÓ ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛÂˆÓ Ú¤ÂÈ Ó· ÂÎÊÚ¿˙ÔÓÙ·È ÛÙÔ ¢ÈÂıÓ¤˜ ™‡ÛÙËÌ· MÔÓ¿‰ˆÓ (SI Units) Î·È ÛÙÔ MÂÙÚÈÎfi (Conventional-™˘Ì‚·ÙÈÎfi) ™‡ÛÙËÌ· ̤۷ Û ·Ú¤ÓıÂÛË. ¶›Ó·Î˜ ÌÂÙ·ÙÚÔ‹˜ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙȘ ‰È¢ı‡ÓÛÂȘ: http://www.icmje.org Î·È http://www.icmje.org/icmje.pdf

™˘ÓÙÔÌÔÁڷʛ˜ OÈ Û˘ÓÙÔÌÔÁڷʛ˜ Ô˘ ¤¯Ô˘Ó ÂÈ‚ÏËı› ‰ÈÂıÓÒ˜, ‰ËÌÔÛȇÔÓÙ·È Û οı Ù‡¯Ô˜ ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡. ™‡ÓıÂÙÔÈ Î·È Ì·ÎÚÔÛÎÂÏ›˜ fiÚÔÈ Ô˘ Â·Ó·Ï·Ì‚¿ÓÔÓÙ·È Û˘¯Ó¿ ÛÙÔ Î›ÌÂÓÔ ÌÔÚÔ‡Ó Ó· ·ÓÙÈηı›ÛÙ·ÓÙ·È ·fi Û˘ÓÙÔÌÔÁڷʛ˜ Ô˘ ÂÂÍËÁÔ‡ÓÙ·È ·fi ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜ Û ÂȉÈÎfi ηٿÏÔÁÔ, Ô ÔÔ›Ô˜ ˘Ô‚¿ÏÏÂÙ·È Ì·˙› Ì ÙËÓ ÂÚÁ·Û›·.

OÈ Û˘ÓÙÔÌÔÁڷʛ˜ ·Ó·Ê¤ÚÔÓÙ·È Û ·Ú¤ÓıÂÛË ÌfiÓÔ ÛÙȘ ÂÚÈÏ‹„ÂȘ.

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

¶ÚÔÛ‰ÈÔÚÈÛÌfi˜ Ù‡Ô˘ ¿ÚıÚÔ˘: Schreiner GF, Lange L. Ethanol modulation of macrophage influx in glomerulonephritis [Abstract]. J Am Soc Nephrol 1991;2:562.

Should antileukotriene therapies be used instead of inhaled corticosteroids in asthma? [Editorial]. Am J Respir Crit Care Med 1998;158:1697-1701.

Laux-End R, Inaebnit D, Gerber HA, Bianchetti MG. Vasculitis associated with levamisole and circulating autoantibodies [Letter]. Arch Dis Child 1996;75:355-356.

II. µπµ§π∞ ∫ÂÊ¿Ï·ÈÔ Û ‚È‚Ï›Ô: Clark AG, Barratt TM. Steroid-responsive nephrotic syndrome. In: Barratt TM, Arner ED, Harmon WE, editors.

Pediatric Nephrology. 4th ed. Baltimore: Lippincott William Wilkins; 1999. p. 742. ™‡ÁÁÚ·ÌÌ· ‹ ÌÔÓÔÁÚ·Ê›·: Gorlin RJ, Cohen MM, Levin LS. Syndromes of the head and neck. 3rd ed. New York: Oxford University Press; 1990.

ñ ÙȘ 70 ÛÙȘ ·Ó·ÛÎÔ‹ÛÂȘ. ñ ÙȘ 30 ÛÙȘ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜. ñ ÙȘ 12 ÛÙ· Â›Î·ÈÚ· ı¤Ì·Ù· Î·È ÙȘ ÂӉȷʤÚÔ˘Û˜ ÂÚÈÙÒÛÂȘ. ñ ÙȘ 5 ÛÙȘ ‚Ú·¯Â›Â˜ ‰ËÌÔÛȇÛÂȘ Î·È ÙȘ ÂÈÛÙÔϤ˜.

¢ËÌÔÛ›Â˘ÛË Û ÙfiÌÔ Ú·ÎÙÈÎÒÓ: Bauer AW. The two definitions of bacterial resistance.

In: Smith AJ, Rogers CA, eds. Proceedings of the Third International Congress of Chemotherapy; 1962 May 29-31; New York: International Society of Chemotherapy; 1963. p.

484-500.

H Û‡ÓÙ·ÍË ÙˆÓ ‚È‚ÏÈÔÁÚ·ÊÈÎÒÓ ·Ú·ÔÌÒÓ Á›ÓÂÙ·È Û‡Ìʈӷ Ì ÙȘ ÚfiÛÊ·Ù· ÙÚÔÔÔÈË̤Ó˜ ÚԉȷÁڷʤ˜ Ù˘ International Committee of Medical Journal

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

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Kaplan SJ. Post hospital home health care: the elderly’s access and utilization [dissertation]. St. Louis (Mo): Washington Univ.; 1995. πππ. CD-ROM Anderson SC, Poulsen KB. Anderson’s electronic atlas of hematology [CD-ROM]. Philadelphia: Lippincott Williams & Wilkins; 2002.

IV. ™∆O ¢π∞¢π∫∆ÀO ÕÚıÚÔ Û ÂÚÈÔ‰ÈÎfi: Abood S. Quality improvement initiative in nursing homes: the ANA acts in an advisory role. Am J Nurs [Internet]. 2002 Jun: Webpage: http://www.nursingworld.org/AJN/2002/june/Wawatch.htm ªÔÓÔÁÚ·Ê›·: Foley KM, Gelband H, editors. Improving palliative care for cancer [Monograph, Internet]. Washington: National Academy Press; 2001. Webpage: http://www.nap.edu/books/0309074029/html

¶›Ó·Î˜ Î·È EÈÎfiÓ˜ AÔÛÙ¤ÏÏÔÓÙ·È ÂȘ ÙÚÈÏÔ‡Ó (¤Ó· ÚˆÙfiÙ˘Ô Î·È ‰‡Ô ʈÙÔ·ÓÙ›ÁÚ·Ê·). ¶Ú¤ÂÈ Ó· ¤¯Ô˘Ó Ï¿ÙÔ˜ ›ÛÔ Ì ÙÔ Ï¿ÙÔ˜ ÙÔ˘ ÌÔÓfiÛÙËÏÔ˘ (7,5 cm) ‹ Ì ÙÔ Ï¿ÙÔ˜ fiÏ˘ Ù˘ ÛÂÏ›‰·˜ (15,5 cm). TÔ Ì¤ÁÈÛÙÔ Ì‹ÎÔ˜ ÙÔ˘˜, Ì·˙› Ì ÙÔ˘˜ Ù›ÙÏÔ˘˜, ‰ÂÓ Ú¤ÂÈ Ó· Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ ·fi 22 cm.

OÈ ›Ó·Î˜ ·ÚÈıÌÔ‡ÓÙ·È Ì ·Ú·‚ÈÎÔ‡˜ ·ÚÈıÌÔ‡˜ Ì ÙË ÛÂÈÚ¿ Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ Î›ÌÂÓÔ. ¶ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ‚Ú·¯‡ Ù›ÙÏÔ Î·È ÂÂÍ‹ÁËÛË ÙˆÓ Û˘ÓÙÌ‹ÛÂˆÓ ÛÙÔ Î¿Ùˆ ̤ÚÔ˜. ™ÙÔ˘˜ ›Ó·Î˜ Ú¤ÂÈ Ó· ·ÔʇÁÔÓÙ·È ÔÈ Î¿ıÂÙ˜ ÁÚ·Ì̤˜. ŸÏÔ ÙÔ ·ÂÈÎÔÓÈÛÙÈÎfi ˘ÏÈÎfi (Û¯‹Ì·Ù·, ‰È·ÁÚ¿ÌÌ·Ù·, ʈÙÔÁڷʛ˜, Î.Ï.) ¯·Ú·ÎÙËÚ›˙ÂÙ·È ˆ˜ ÂÈÎfiÓ˜ Î·È ı· Ú¤ÂÈ Ó· Â›Ó·È ¿ÚÈÛÙ˘ ÔÈfiÙËÙ·˜. ™ÙÔ ›Ûˆ ̤ÚÔ˜ ÙˆÓ ÂÈÎfiÓˆÓ Ú¤ÂÈ Ó· ÛËÌÂÈÒÓÂÙ·È Ì ÌÔχ‚È Ô ·ÚÈıÌfi˜ Ù˘ ÂÈÎfiÓ·˜ Î·È ÙÔ fiÓÔÌ· ÙÔ˘ ÚÒÙÔ˘ Û˘ÁÁڷʤ·, ηıÒ˜ Î·È ¤Ó· ‚¤ÏÔ˜ ÙÔ ÔÔ›Ô Ó· ‰Â›¯ÓÂÈ ÙÔ ¿Óˆ ̤ÚÔ˜ Ù˘ ÂÈÎfiÓ·˜. ™ÙȘ ʈÙÔÁڷʛ˜ ·ÛıÂÓÒÓ ‰ÂÓ Ú¤ÂÈ Ó· ·Ó·ÁÓˆÚ›˙ÂÙ·È Ë Ù·˘ÙfiÙËÙ¿ ÙÔ˘˜. OÈ ·ÛıÂÓ›˜ ‰ÂÓ Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È ÔÓÔÌ·ÛÙÈο.

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

°. ÀÔ‚ÔÏ‹ Î·È ¢ËÌÔÛ›Â˘ÛË ÙˆÓ ∂ÚÁ·ÛÈÒÓ ŸÏ˜ ÔÈ ÂÚÁ·Û›Â˜ Ú¤ÂÈ Ó· ˘Ô‚¿ÏÏÔÓÙ·È ÂȘ ÙÚÈÏÔ‡Ó Î·È Ó· Û˘Óԉ‡ÔÓÙ·È ·fi ‰ÈÛΤٷ ‹ CD, ηıÒ˜ Î·È ·fi ÂÈÛÙÔÏ‹, Ë ÔÔ›· ı· Û˘Ó˘ÔÁÚ¿ÊÂÙ·È ·fi fiÏÔ˘˜ ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜, ÛÙËÓ ÔÔ›· ı· ‰ËÏÒÓÂÙ·È fiÙÈ Ë ÂÚÁ·Û›· ‰ÂÓ ¤¯ÂÈ ÂÓ Ì¤ÚÂÈ ‹ ÂÍ ÔÏÔÎÏ‹ÚÔ˘ ‰ËÌÔÛÈ¢ı› ‹ ˘Ô‚ÏËı› ÁÈ· ÎÚ›ÛË Û ¿ÏÏÔ ÂÚÈÔ‰ÈÎfi Î·È fiÙÈ ÔÈ Û˘ÁÁÚ·Ê›˜ ÂÁÎÚ›ÓÔ˘Ó ÙË ‰ËÌÔÛ›Â˘Û‹ Ù˘ ÛÙÔ ÂÚÈÔ‰ÈÎfi “¶·È‰È·ÙÚÈ΋”. ∂ÈϤÔÓ, ı· Ú¤ÂÈ Ó· ·Ó·Ê¤ÚÔÓÙ·È Ù˘¯fiÓ ÂȉÔÙ‹ÛÂȘ-¯ÔÚËÁ›Â˜ ‹ ¿ÏϘ ËÁ¤˜ ˘ÔÛÙ‹ÚÈ͢.

EÊfiÛÔÓ Ë ÂÚÁ·Û›· Á›ÓÂÈ ·Ô‰ÂÎÙ‹, ÙÔ ‰ÈÔÚıˆÌ¤ÓÔ Û‡Ìʈӷ Ì ÙȘ ˘ԉ›ÍÂȘ ÙˆÓ ÎÚÈÙÒÓ Î·È ÂÎ Ó¤Ô˘ ‰·ÎÙ˘ÏÔÁÚ·ÊË̤ÓÔ Î›ÌÂÓÔ Ú¤ÂÈ Ó· ˘Ô‚¿ÏÂÙ·È ÛÙË ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹, Û˘Óԉ¢fiÌÂÓÔ ·fi ‰ÈÛΤٷ ‹ CD Ô˘ Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ ÂÚÁ·Û›· Û ÚfiÁÚ·ÌÌ· Word, ηıÒ˜ Î·È ÂÈÛÙÔÏ‹ fiÔ˘ Ó· ·Ó·Ê¤ÚÔÓÙ·È ·Ó·Ï˘ÙÈο ÔÈ ÙÚÔÔÔÈ‹ÛÂȘ ‹ ÔÈ ·ÓÙÈÚÚ‹ÛÂȘ ÛÙȘ ÚÔÙ¿ÛÂȘ ÙˆÓ ÎÚÈÙÒÓ.

H ηı˘ÛÙ¤ÚËÛË Ù˘ Â·Ó˘Ô‚ÔÏ‹˜ ÙÔ˘ ÙÚÔÔÔÈË̤ÓÔ˘ ÎÂÈ̤ÓÔ˘ ¤Ú·Ó ÙˆÓ 30 ËÌÂÚÒÓ Û˘ÓÂ¿ÁÂÙ·È Ó¤· ˘Ô‚ÔÏ‹.

T· ¤ÍÔ‰· ÙˆÓ ÊÈÏÌ Î·È ÙˆÓ ·Ó·Ù‡ˆÓ ‚·Ú‡ÓÔ˘Ó ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜ Î·È Ú¤ÂÈ Ó· ÏËÚÒÓÔÓÙ·È Ì ÙËÓ ·ÔÛÙÔÏ‹ ÙÔ˘ ÚÒÙÔ˘ ‰ÔÎÈÌ›Ô˘ ηÙ¢ı›·Ó ÛÙÔÓ Ù˘ÔÁÚ¿ÊÔ.

T· ΛÌÂÓ· ÙˆÓ ÂÚÁ·ÛÈÒÓ Ô˘ ‰ÂÓ Á›ÓÔÓÙ·È ·Ô‰ÂÎÙ¤˜ ÁÈ· ‰ËÌÔÛ›Â˘ÛË, ‰ÂÓ ÂÈÛÙÚ¤ÊÔÓÙ·È. MÔÚ› Ó· ÂÈÛÙÚ·ÊÔ‡Ó, ÂÊfiÛÔÓ ˙ËÙËı› ÂÓÙfi˜ ÂÍ·Ì‹ÓÔ˘, Ù· Û¯‹Ì·Ù· Î·È ÔÈ ÊˆÙÔÁڷʛ˜ Ô˘ Ù· Û˘Óԉ‡ԢÓ.

OÈ ÂÚÁ·Û›Â˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È ÚÔ˜ ÎÚ›ÛË ÁÈ· ‰ËÌÔÛ›Â˘ÛË ÛÙÔ ÂÚÈÔ‰ÈÎfi “¶·È‰È·ÙÚÈ΋” ·ÔÛÙ¤ÏÏÔÓÙ·È ÂȘ ÙÚÈÏÔ‡Ó ÛÙË ‰È‡ı˘ÓÛË: ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹, EÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ EÙ·ÈÚ›· Mȯ·Ï·ÎÔÔ‡ÏÔ˘ 92, 115 28 Aı‹Ó·

¶ÚÈÓ ·ÔÛÙ›ÏÂÙ ÙËÓ ÂÚÁ·Û›· Û·˜, ‚‚·Èˆı›Ù fiÙÈ ÂÚÈÏ·Ì‚¿ÓÂÈ: 1. 3 ·ÓÙ›ÁÚ·Ê· ÙÔ˘ ÎÂÈ̤ÓÔ˘ Ù˘ ÂÚÁ·Û›·˜, Ù˘ˆÌ¤Ó· Û‡Ìʈӷ Ì ÙȘ Ô‰ËÁ›Â˜.

2. ¢ÈÛΤٷ ‹ CD Ì fiÏÔ ÙÔ ˘ÏÈÎfi Ù˘ ÂÚÁ·Û›·˜ (ΛÌÂÓÔ, ›Ó·Î˜, ÂÈÎfiÓ˜).

3. ∂ÈÛÙÔÏ‹ ˘Ô‚ÔÏ‹˜ Î·È ‰‹ÏˆÛË ÌË ÚÔÁÂÓ¤ÛÙÂÚ˘ ‰ËÌÔÛ›Â˘Û˘ Ù˘ ÂÚÁ·Û›·˜.

4. ™ÂÏ›‰· Ù›ÙÏÔ˘ (¯ˆÚÈÛÙ‹ ÛÂÏ›‰·) ÂÚÈÏ·Ì‚¿ÓÂÈ: ·.Ù›ÙÏÔ Î·È ‚Ú·¯‡ Ù›ÙÏÔ ÂÚÁ·Û›·˜ ‚.fiÓÔÌ· Î·È ÂÒÓ˘ÌÔ Û˘ÁÁڷʤˆÓ (ÔÏÔÁڿʈ˜) Á. ÂÈÛÙËÌÔÓÈÎfi/¿ ΤÓÙÚÔ/· fiÔ˘ ¤ÁÈÓÂ Ë ÂÚÁ·Û›· ‰.fiÓÔÌ·, ‰È‡ı˘ÓÛË Î·È ÙËϤʈÓÔ Û˘ÁÁڷʤ· ÁÈ· ·ÏÏËÏÔÁÚ·Ê›·.

5. ¶ÂÚ›ÏË„Ë ÂÏÏËÓÈ΋-·ÁÁÏÈ΋, ‰ÔÌË̤ÓË ÛÙȘ ÂÍ‹˜ ·Ú·ÁÚ¿ÊÔ˘˜: ÂÈÛ·ÁˆÁ‹, ̤ıÔ‰ÔÈ, ·ÔÙÂϤÛÌ·Ù· Î·È Û˘ÌÂÚ¿ÛÌ·Ù·, ηıÒ˜ Î·È Ï¤ÍÂȘ ÎÏÂȉȿ (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·).

6. ∫·Ù¿ÏÔÁÔ Û˘ÓÙÔÌÔÁÚ·ÊÈÒÓ (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·).

7. ∫›ÌÂÓÔ (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·).

8. ∂˘¯·ÚÈÛٛ˜ ‹ ·Ó·ÁÓˆÚ›ÛÂȘ (·Ó·ÊÔÚ¿ Û ÂȉÔÙ‹ÛÂȘ-¯ÔÚËÁ›Â˜ ‹ ¿ÏϘ ËÁ¤˜ ˘ÔÛÙ‹ÚÈ͢).

9. µÈ‚ÏÈÔÁÚ·Ê›· (‰ÈÏfi ‰È¿ÛÙËÌ· - ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·).

10. ¶›Ó·Î˜ (Ô Î·ı¤Ó·˜ Û ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·) ÂȘ ÙÚÈÏÔ‡Ó.

11. ∂ÈÎfiÓ˜, Ì ‚¤ÏÔ˜ ÛÙÔ ›Ûˆ ̤ÚÔ˜ ÙÔ ÔÔ›Ô Ó· ‰Â›¯ÓÂÈ ÚÔ˜ Ù· Â¿Óˆ, ·ÚÈıÌË̤Ó˜, ÂȘ ÙÚÈÏÔ‡Ó.

12. ∆›ÙÏÔ˘˜ ÂÈÎfiÓˆÓ (‰ÈÏfi ‰È¿ÛÙËÌ· - Ô Î·ı¤Ó·˜ Û ¯ˆÚÈÛÙ‹ ÛÂÏ›‰·) ÂȘ ÙÚÈÏÔ‡Ó.

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™À¡∆√ª√°ƒ∞ºπ∂™ o

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

ABBREVIATIONS

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

™˘Ó‰˘·˙fiÌÂÓ· ÚÔı¤Ì·Ù·

Combining prefixes

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

T G M k h da d c m Ì n p f a

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

INSTRUCTIONS TO AUTHORS A. General Information The Greek Paediatric Society is the owner of “Paediatriki”, its official scientific journal, which is distributed to its members. Its objectives are the publication of paediatric scientific work and the continuing education of paediatricians. For this purpose, it publishes a variety of articles, and in particular: 1. Editorials (upon invitation by the Editorial Board).

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Regarding papers on current issues, the author’s request for immediate publication should be quoted on the first page. The Editorial Board reserves the right to accept such papers for immediate publication.

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should be typed on one side of blank paper format A4 (21x29.7 cm), double line spacing and minimum indent 2.5 cm on both sides.

The paper should have the following structure: title page, short title, abstract in Greek and English, list of abbreviations, text, acknowledgements and quoting of grants, sponsorships or other financial support sources, references, tables, figures, figure legends. Each of these sections should be started on a new page. Pages should be numbered consecutively, beginning with the title page.

Text length shall be: ñ review articles 2000-3000 words; ñ original articles 1500-2500 words and case reports 1000-1500 words; ñ brief reports 1000-1500 words; ñ letters 250-500 words.

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Abstracts The abstract should summarize the objectives, methodology, main results and conclusions of the study. ñ It should contain at least 200 words, and not exceed 250 words. ñ It should consist of the following paragraphs: background, methods, results and conclusions.

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Text Original articles include: introduction, methods, results and discussion. The introduction includes the latest research data on the subject and the main references and the objectives of the paper. The description of the methods should be precise and detailed so as to enable reproduction by other researchers. In addition, the statistical methods of analysis and evaluation of the results should be described. Results should be presented clearly, together with the appropriate statistical analysis. Discussion should cover the results ensuing from the research, their significance and possible associations with the observations of other researchers.

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Thanks or acknowledgements (reference to grants, sponsorships or other sources of financial support) should be quoted at the end of the text, before references.

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

II. BOOKS Chapter in book: Clark AG, Barratt TM. Steroid-responsive nephrotic syndrome. In: Barratt TM, Arner ED, Harmon WE, editors.

Pediatric Nephrology. 4th ed. Baltimore: Lippincott William Wilkins; 1999. p. 742.

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

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

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In listing references follow the recently modified standards of the International Committee of Medical Journal Editors/Uniform Requirements for Manuscripts Submitted to Biomedical Journals, (http://www.icmje.org and http:// www.icmje.org/icmje.pdf). Abbreviated names of journals should conform to the Cumulated Index Medicus [List of Journals Indexed in Index Medicus (http://www.nlm.nih.gov/bsd/uniform_requirements.html)].

Examples of reference style I. JOURNALS All authors are cited if they are six or less; if they are 7 or more, the first six are cited, followed by “et al”.

Regular edition: Proesmans W. Bartter syndrome and its neonatal variant. Eur J Pediatr 1997;156:669-679.

Supplement issue: Flyvbjerg A. Role of growth hormone, insulin-like growth factors (IGFs) and IGF-binding proteins in the renal complications of diabetes. Kidney Int 1997;52 (60 Suppl):S12-S19.

No author: National Institutes of Health Consensus Development Conference. Neurofibromatosis conference statement. Arch Neurol 1988;45:575-578.

Article type specification: Schreiner GF, Lange L. Ethanol modulation of macrophage influx in glomerulonephritis [Abstract]. J Am Soc Nephrol 1991;2:562.

Should antileukotriene therapies be used instead of inhaled corticosteroids in asthma? [Editorial]. Am J Respir Crit Care Med 1998;158:1697-1701.

Laux-End R, Inaebnit D, Gerber HA, Bianchetti MG. Vasculitis associated with levamisole and circulating autoantibodies [Letter]. Arch Dis Child 1996;75:355-356.

Publication in a volume of proceedings: Bauer AW. The two definitions of bacterial resistance.

In: Smith AJ, Rogers CA, eds. Proceedings of the Third International Congress of Chemotherapy; 1962 May 29-31; New York: International Society of Chemotherapy; 1963. p.

484-500.

Doctoral dissertation: Kaplan SJ. Post hospital home health care: the elderly’s access and utilization [dissertation]. St. Louis (Mo): Washington Univ.; 1995. πππ. CD-ROM Anderson SC, Poulsen KB. Anderson’s electronic atlas of hematology [CD-ROM]. Philadelphia: Lippincott Williams & Wilkins; 2002.

IV. ON THE INTERNET Article in journal Abood S. Quality improvement initiative in nursing homes: the ANA acts in an advisory role. Am J Nurs [Internet]. 2002 Jun: Webpage: http://www.nursingworld.org/ AJN/2002/june/Wawatch.htm Monograph Foley KM, Gelband H, editors. Improving palliative care for cancer [Monograph, Internet]. Washington: National Academy Press; 2001. Webpage: http://www.nap.edu/books/0309074029/html Websites Cancer-Pain.org [Webpage, Internet]. New York: Association of Cancer Online Resources, Inc.; 2002: http://www.cancer-pain.org/ Tables and Figures Three copies should be submitted (original plus 2 copies). Their width should either be equal to the width of one column (7.5 cm) or to the width of the page (15.5 cm).

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π·ÙÚÈ΋ ‚·ÛÈṲ̂ÓË ÛÙȘ ÂӉ›ÍÂȘ ∆È ·ÏÏ¿˙ÂÈ ÛÙËÓ È·ÙÚÈ΋ Ú¿ÍË; ™. ∏Ï›·, µ. ∞ÁÁÂÏ¿ÎÔ˘

¶ÂÚ›ÏË„Ë: ∏ π·ÙÚÈ΋ µ·ÛÈṲ̂ÓË ÛÙȘ ∂Ӊ›ÍÂȘ (πµ∂) Â›Ó·È Ë “Â˘Û˘Ó›‰ËÙË, Û·Ê‹˜ Î·È Û˘ÓÂÙ‹ ¯Ú‹ÛË ÙˆÓ ÈÔ ÚfiÛÊ·ÙˆÓ Î·È ÈÔ ·ÍÈfiÈÛÙˆÓ Â˘ÚËÌ¿ÙˆÓ Ù˘ ÙÚ¤¯Ô˘Û·˜ È·ÙÚÈ΋˜ ¤Ú¢ӷ˜ ÛÙË Ï‹„Ë ·ÔÊ¿ÛÂˆÓ ÁÈ· ÙËÓ ÂÚ›ı·Ï„Ë ÙÔ˘ οı ·ÛıÂÓÔ‡˜ ˆ˜ ͯˆÚÈÛÙ‹˜ ÔÓÙfiÙËÙ·˜”, fiˆ˜ ÂÚÈÁÚ¿ÊËΠ·fi ÙÔÓ Sackett Î·È Û˘Ó. ∏ ·Ó·ÁηÈfiÙËÙ· ÙˆÓ ÛËÌÂÚÈÓÒÓ ÎÏÈÓÈÎÒÓ ÁÈ·ÙÚÒÓ Ó· ˘ÔÛÙËÚ›˙Ô˘Ó ϤÔÓ ÙȘ ·ÔÊ¿ÛÂȘ ÙÔ˘˜ Ì ÂÈÛÙËÌÔÓÈο ·Î¤Ú·È˜ ÂӉ›ÍÂȘ, ÏfiÁˆ ÙˆÓ Û˘Ó¯Ҙ ·˘Í·ÓfiÌÂÓˆÓ È·ÙÚÈÎÒÓ ÏËÚÔÊÔÚÈÒÓ, ¤‰ˆÛ Á¤ÓÂÛË ÛÙËÓ È‰¤· ·˘Ù‹. ∏ ‰È·‰Èηۛ· πµ∂ ¤¯ÂÈ ÙË ‚¿ÛË Ù˘ Û ¤Ó· ÎÏÈÓÈÎfi Úfi‚ÏËÌ· Ô˘ ·ÓÙÈÌÂÙˆ›˙ÂÈ ¤Ó·˜ È·ÙÚfi˜, Ì·˙› Ì ÙÔÓ ·ÛıÂÓ‹ ÙÔ˘, Î·È ·ÎÔÏÔ˘ı› Ù· ÂÍ‹˜ ‚‹Ì·Ù·: ·Ú¯Èο ÌÂÙ·ÙÚ¤ÂÙ·È ÙÔ ÎÏÈÓÈÎfi Úfi‚ÏËÌ· Û ̛· Û·ÊÒ˜ ‰È·Ù˘ˆÌ¤ÓË ÂÚÒÙËÛË, Ë ÔÔ›· ¯ÚËÛÈÌÔÔÈÂ›Ù·È ˆ˜ ‚¿ÛË ÁÈ· ÙË ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·˙‹ÙËÛË. ∞ÎÔÏÔ˘ı› Ë ¤Ú¢ӷ ÙˆÓ ÈÔ ·ÍÈfiÈÛÙˆÓ ËÁÒÓ ÏËÚÔÊÔÚÈÒÓ ÛÙÔ ¢È·‰›ÎÙ˘Ô ÁÈ· ÙËÓ ·Ó‡ÚÂÛË ÙˆÓ Î·Ï‡ÙÂÚˆÓ ÂӉ›ÍˆÓ. ™ÙË Û˘Ó¤¯ÂÈ· ·ÍÈÔÏÔÁÔ‡ÓÙ·È ÔÈ ÂӉ›ÍÂȘ ·˘Ù¤˜, fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÁ΢ÚfiÙËÙ· Î·È ÙËÓ ·ÍÈÔÈÛÙ›· ÙÔ˘˜. ∆ÂÏÂ˘Ù·›Ô ‚‹Ì· ÛÙËÓ ‰È·‰Èηۛ· πµ∂ Â›Ó·È Ë ÂÊ·ÚÌÔÁ‹ ÙˆÓ Î·Ï‡ÙÂÚˆÓ ÂӉ›ÍÂˆÓ ÛÙȘ ȉȷ›ÙÂÚ˜ ·Í›Â˜, ÚÔÙÈÌ‹ÛÂȘ Î·È ÚÔÛ‰Ô˘ ÙÔ˘ οı ·ÛıÂÓÔ‡˜. ∞˘Ùfi ÙÔ ¿ÚıÚÔ ÛÎÔfi ¤¯ÂÈ Ó· ÂÚÈÁÚ¿„ÂÈ ·Ó·Ï˘ÙÈο Ù· ‚‹Ì·Ù· Ù˘ πµ∂ Î·È Ó· ‰È¢ÎÚÈÓ›ÛÂÈ, Ò˜ Ë Ó¤· ·˘Ù‹ È·ÙÚÈ΋ Ú·ÎÙÈ΋ ÁÂÊ˘ÚÒÓÂÈ ÙÔ ¯¿ÛÌ· ÌÂٷ͇ ÎÏÈÓÈ΋˜ ‰Ú¿Û˘ Î·È È·ÙÚÈ΋˜ ¤Ú¢ӷ˜ Î·È Î·Ù·Ê¤ÚÓÂÈ Ó· ‰ÒÛÂÈ ··ÓÙ‹ÛÂȘ ÛÙ· ηıËÌÂÚÈÓ¿ ÎÏÈÓÈο ÚÔ‚Ï‹Ì·Ù· ‚ÂÏÙÈÒÓÔÓÙ·˜ ¤ÙÛÈ ÙËÓ È·ÙÚÈ΋ ÂÚ›ı·Ï„Ë.

A’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, µÂÓÈ˙¤ÏÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ ∫Ú‹Ù˘ AÏÏËÏÔÁÚ·Ê›·: ™Ù·˘ÚԇϷ ∏Ï›· A’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ §ÂˆÊfiÚÔ˜ ∫ÓˆÛÔ‡, ∆.∫. 714 09 ∏Ú¿ÎÏÂÈÔ, ∫Ú‹ÙË ∆.£. 44 E-mail: stayrinah@hotmail.com ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 05-07-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 10-02-2006

§¤ÍÂȘ ÎÏÂȉȿ: π·ÙÚÈ΋ ‚·ÛÈṲ̂ÓË ÛÙȘ ÂӉ›ÍÂȘ, ¢È·‰›ÎÙ˘Ô, ¤Ú¢ӷ, Û˘ÛÙËÌ·ÙÈ΋ ·Ó·ÛÎfiËÛË, ÎÚÈÙÈ΋ ·ÍÈÔÏfiÁËÛË.

Evidence based medicine - What changes in clinical practice?

S. Ilia, V. Agelakou

Abstract: Evidence based medicine (EBM) is founded on the idea that decisions about the care of individual patients should encompass the "conscientious, explicit and judicious use of current best evidence", as outlined by Sackett and colleagues. The concept of EBM emerged as clinicians were obliged to integrate an ever-increasing amount of medical information into the clinical decision-making process. The EBM process concerns the clinical problem faced by a clinician and a patient and consists of specific steps. Initially, the practitioner should convert the clinical problem into a well-formulated answerable question, which can be used to run a literature search. According to the clinical query, the best evidence should be found by searching the most reputable sources of information on the Internet.

The next step is to critically appraise the evidence and decide about its validity and reliability. The final step is to integrate the best evidence with clinical expertise and to apply it, taking into consideration the relevant values, preferences and expectations of the individual patient. This review describes the elements of EBM and demonstrates how they can be incorporated into clinical problems in a way which improves healthcare delivery and bridges the gap between medical practice and research.

Ist Pediatric Clinic, General Hospital “Venizeleio”, Herakleion, Crete Correspondence: Stavroula Ilia 1st Pediatric Clinic Knossos Av, 714 09 Herakleion, Crete P.o. Box 44 E-mail: stayrinah@hotmail.com Date of submission: 05-07-2005 Date of approval: 10-02-2006

Key words: Evidence based medicine, Internet, research, systematic review, critical appraisal.

™˘ÓÙÔÌÔÁڷʛ˜ πµ∂ π·ÙÚÈ΋ µ·ÛÈṲ̂ÓË ÛÙȘ ∂Ӊ›ÍÂȘ (∂µª) ∆∂ª ∆˘¯·ÈÔÔÈË̤Ó˜ ∂ÏÂÁ¯fiÌÂÓ˜ ªÂϤÙ˜ (RCTs) ™∞ ™˘ÛÙËÌ·ÙÈ΋ ∞Ó·ÛÎfiËÛË

ª∞ √ªø ∂√º MeSH

ªÂÙ·-·Ó¿Ï˘ÛË √Í›· ª¤ÛË øÙ›Ùȉ· ∂ıÓÈÎfi˜ √ÚÁ·ÓÈÛÌfi˜ º·ÚÌ¿ÎˆÓ Medical Subject Headings

CATs Critically Appraised Topics ¶·È‰È·ÙÚÈ΋ 2006;69:247-254

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™. ∏Ï›·, µ. ∞ÁÁÂÏ¿ÎÔ˘

EÈÛ·ÁˆÁ‹ ∏ ¤ÓÓÔÈ· “π·ÙÚÈ΋ µ·ÛÈṲ̂ÓË ÛÙȘ ∂Ӊ›ÍÂȘ” (πµ∂) (Evidence Based Medicine) ÔÚ›ÛÙËΠÚÒÙË ÊÔÚ¿ ·fi ÌÈ· ÔÌ¿‰· ÎÏÈÓÈÎÒÓ ÂȉËÌÈÔÏfiÁˆÓ ÙÔ 1990, (D. Sackett Î·È Û˘Ó., ¶·ÓÂÈÛÙ‹ÌÈÔ McMaster, ∫·Ó·‰¿˜), ÔÈ ÔÔ›ÔÈ ‰È·›ÛÙˆÛ·Ó ÙËÓ ·Ó·ÁηÈfiÙËÙ·, Û Ú·ÎÙÈÎfi Â›Â‰Ô È·, Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ·ÍÈfiÈÛÙ˜ Î·È ÙÂÎÌËÚȈ̤Ó˜ ÏËÚÔÊÔڛ˜ Ù˘ È·ÙÚÈ΋˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ Î·È ¤Ú¢ӷ˜ ‰›Ï· ÛÙÔ ÎÚ‚¿ÙÈ ÙÔ˘ ·ÛıÂÓÔ‡˜ (1). ∏ ‰È·‰Èηۛ· πµ∂ ÔÚ›ÛÙËΠˆ˜ Ë “Â˘Û˘Ó›‰ËÙË, Û·Ê‹˜ Î·È Û˘ÓÂÙ‹ ¯Ú‹ÛË ÙˆÓ ÈÔ ÚfiÛÊ·ÙˆÓ Î·È ÈÔ ·ÍÈfiÈÛÙˆÓ Â˘ÚËÌ¿ÙˆÓ Ù˘ ÙÚ¤¯Ô˘Û·˜ È·ÙÚÈ΋˜ ¤Ú¢ӷ˜ ÛÙË Ï‹„Ë ·ÔÊ¿ÛÂˆÓ ÁÈ· ÙËÓ ÂÚ›ı·Ï„Ë ÙÔ˘ οı ·ÛıÂÓÔ‡˜ ˆ˜ ȉȷ›ÙÂÚË ÚÔÛˆÈÎfiÙËÙ·” (2). ∏ ‰È·‰Èηۛ· πµ∂ ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· ·ÎfiÏÔ˘ı· ‚‹Ì·Ù· (¶›Ó·Î·˜ 1): 1. ∞Ó·ÁÓÒÚÈÛË ÙÔ˘ ÎÏÈÓÈÎÔ‡ ÚÔ‚Ï‹Ì·ÙÔ˜ Î·È ÌÂÙ·ÙÚÔ‹ ·˘ÙÔ‡ Û ۈÛÙ¿ ‰ÔÌË̤ÓÔ Î·È Î·Ï¿ ÂÛÙÈ·Ṳ̂ÓÔ ÎÏÈÓÈÎfi ÂÚÒÙËÌ·.

2. ∞Ó¿Ù˘ÍË ÛÙÚ·ÙËÁÈÎÒÓ ÁÈ· ·ÔÙÂÏÂÛÌ·ÙÈ΋ ·Ó·˙‹ÙËÛË ÙˆÓ Î·Ï‡ÙÂÚ· ÙÂÎÌËÚÈˆÌ¤ÓˆÓ ÂÈÛÙËÌÔÓÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ (best evidence) ÛÙËÓ È·ÙÚÈ΋ ‚È‚ÏÈÔÁÚ·Ê›·, Ô˘ ÂӉ¯Ô̤ӈ˜ ı· ‰ÒÛÔ˘Ó ·¿ÓÙËÛË ÛÙÔ ÎÏÈÓÈÎfi ÂÚÒÙËÌ·.

3. ∫ÚÈÙÈ΋ ·ÍÈÔÏfiÁËÛË ÙˆÓ ‚ÈÔ˚·ÙÚÈÎÒÓ ‰ËÌÔÛÈÂ˘Ì¿ÙˆÓ Ô˘ ·Ó¤‰ÂÈÍÂ Ë ¤Ú¢ӷ, fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÁ΢ÚfiÙËÙ· Î·È ÙËÓ ÏËÚfiÙËÙ· ÙˆÓ ÏËÚÔÊÔÚÈÒÓ Ô˘ ÚÔÛʤÚÔ˘Ó Î·ıÒ˜ Î·È ÙËÓ ·ÓÙÈÛÙÔȯ›· ÙÔ˘˜ Ì ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ÎÏÈÓÈÎfi ÂÚÒÙËÌ·.

4. ∂Ê·ÚÌÔÁ‹ ÙˆÓ Î·Ï‡ÙÂÚˆÓ ÂӉ›ÍÂˆÓ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË, ÛÂ Û˘Ó‰˘·ÛÌfi ¿ÓÙÔÙÂ, Ì ٷ ȉȷ›ÙÂÚ· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ οı ·ÛıÂÓÔ‡˜.

5. ∞ÍÈÔÏfiÁËÛË ÙÔ˘ ·ÔÙÂϤÛÌ·ÙÔ˜ ÌÂÙ¿ ·fi ·˘Ù‹ ÙËÓ ÔÚıÔÏÔÁÈο ‰ÔÌË̤ÓË Î·È Û˘ÛÙËÌ·ÙÈ΋ ÚÔÛ¤ÁÁÈÛË ÙˆÓ ÎÏÈÓÈÎÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ Î·È Ï‹„Ë ÎÏÈÓÈÎÒÓ ·ÔÊ¿ÛÂˆÓ ÌÂÙ¿ ·fi ÙËÓ Î·Ï‡ÙÂÚË ÏËÚÔÊfiÚËÛË (3). ∞Ú¯Èο ÌÔÚ› Ó· Ê·›ÓÂÙ·È Ì›· ÔχÏÔÎË Î·È Ó¤· ‰È·‰Èηۛ·, ÛÙËÓ Ú·ÁÌ·ÙÈÎfiÙËÙ· ¶›Ó·Î·˜ 1. µ‹Ì·Ù· πµ∂ ∞Ó·Ï˘ÙÈο ÛÙ¿‰È· ‰È·‰Èηۛ·˜ πµ∂ 1. ªÂÙ·ÙÚÔ‹ ÎÏÈÓÈÎÔ‡ ÚÔ‚Ï‹Ì·ÙÔ˜ Û ۈÛÙ¿ ‰ÔÌË̤ÓË ÂÚÒÙËÛË 2. ∞Ó·˙‹ÙËÛË Î·Ï‡ÙÂÚˆÓ ÂÈÛÙËÌÔÓÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ 3. ∫ÚÈÙÈ΋ ·ÍÈÔÏfiÁËÛË ÂÈÛÙËÌÔÓÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ 4. ∂Ê·ÚÌÔÁ‹ ÙˆÓ Î·Ï‡ÙÂÚˆÓ ÂӉ›ÍÂˆÓ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË 5. ∞ÍÈÔÏfiÁËÛË ·ÔÙÂϤÛÌ·ÙÔ˜ ¶·È‰È·ÙÚÈ΋ 2006;69:247-254

fï˜, Â›Ó·È Ì›· ÛÂÈÚ¿ ÁÂÁÔÓfiÙˆÓ Ô˘ Û˘Ó¤‚·ÈÓ ¿ÓÙÔÙ ÛÙ· È·ÙÚÈο Ú·ÎÙÈο. ¶·Ï·ÈfiÙÂÚ· Ë Ï‹„Ë ÎÏÈÓÈÎÒÓ ·ÔÊ¿ÛÂˆÓ ‚·ÛÈ˙fiÙ·Ó ÌfiÓÔ Û ȷÙÚÈο ‚È‚Ï›·, οÔÈ· ·fi ·˘Ù¿ ›Ûˆ˜ Ó· ¯ÚÔÓÔÏÔÁÔ‡ÓÙ·Ó Î·È ·fi ‰ÂηÂÙÈÒÓ (!), ‰ÈÂıÓ‹ È·ÙÚÈο ÂÚÈÔ‰Èο, Ô˘ fï˜ Ë ÚfiÛ‚·ÛË ÛÙ· ÙÂÏÂ˘Ù·›· ‹Ù·Ó ÂÚÈÔÚÈṲ̂ÓË ·fi ÙÔ˘˜ ÂÚÈÛÛfiÙÂÚÔ˘˜ ÁÈ·ÙÚÔ‡˜, fiˆ˜ Â›Û˘ Î·È ÛÙËÓ ÚÔÛˆÈ΋ ›ڷ ÙÔ˘ οı ÎÏÈÓÈÎÔ‡. ™‹ÌÂÚ·, Ô Ó¤Ô˜ È·ÙÚfi˜, ÏfiÁˆ ÂÎÚËÎÙÈ΋˜ ·Ó¿Ù˘Í˘ ÙÔ˘ ¢È·‰ÈÎÙ‡Ô˘, ¤¯ÂÈ ÚfiÛ‚·ÛË Û ÌÂÁ¿ÏÔ fiÁÎÔ Ù˘ È·ÙÚÈ΋˜ ‚È‚ÏÈÔÁÚ·Ê›·˜, ÂÎÛ˘Á¯ÚÔÓ›˙ÂÈ Û˘Ó¯Ҙ ÙȘ ÁÓÒÛÂȘ ÙÔ˘, ÂÍÔÈÎÂÈÒÓÂÙ·È Ì ÌÂıfi‰Ô˘˜ Ù˘ ÎÏÈÓÈ΋˜ ¤Ú¢ӷ˜, ÙËÚ› ÎÚÈÙÈ΋ ÛÙ¿ÛË ·¤Ó·ÓÙÈ ÛÙ· ÂÚ¢ÓËÙÈο ·ÔÙÂϤÛÌ·Ù· Î·È Â›Ó·È Û›ÁÔ˘ÚÔ˜ ÁÈ· ÙË ÏÔÁÈ΋ ÂÍ‹ÁËÛË Î·È ÔÚıfiÙËÙ· ÙˆÓ ·ÔÊ¿ÛÂÒÓ ÙÔ˘ (4). ŒÙÛÈ ·ÎÔÏÔ˘ıÂ›Ù·È ÌÈ· ÈÔ ·‰ÔÁÌ¿ÙÈÛÙË, ÈÔ Û˘ÛÙËÌ·ÙÈ΋, ÈÔ ·Ó·Ï˘ÙÈ΋ Î·È ÈÔ ·˘ÛÙËÚ‹ ÌÂıÔ‰ÔÏÔÁ›· Ï‹„˘ ÎÏÈÓÈÎÒÓ ·ÔÊ¿ÛˆÓ. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ‰È·‰Èηۛ· πµ∂ ¤ÁÎÂÈÙ·È ÛÙË Û˘ÛÙËÌ·ÙÈ΋ ·Ó‡ÚÂÛË, ·ÍÈÔÏfiÁËÛË Î·È ÂÊ·ÚÌÔÁ‹ ÙˆÓ ·ÓÙ›ÛÙÔȯˆÓ ¢ÚËÌ¿ÙˆÓ Ù˘ ÙÚ¤¯Ô˘Û·˜ ¤Ú¢ӷ˜ ÛÙÔ ÂοÛÙÔÙ ÎÏÈÓÈÎfi Úfi‚ÏËÌ·.

∆Ô ÎÏÈÓÈÎfi ÂÚÒÙËÌ· ∆Ô ÈÔ ÛËÌ·ÓÙÈÎfi ‚‹Ì· ÛÙË ‰È·‰Èηۛ· πµ∂ Â›Ó·È Ë ÌÂÙ·ÙÚÔ‹ ÙÔ˘ ÎÏÈÓÈÎÔ‡ ÚÔ‚Ï‹Ì·ÙÔ˜ Û ۈÛÙ¿ ‰ÔÌË̤ÓÔ ÂÚÒÙËÌ· (frame question). ªÂÙ¿ ÙË Ï‹„Ë ÈÛÙÔÚÈÎÔ‡ Î·È ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË ·Ó·‰‡ÔÓÙ·È ÔÏÏ¿ ÂÚˆÙ‹Ì·Ù· Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË ‰È¿ÁÓˆÛË, ÙË ıÂÚ·›·, ÙËÓ ÚfiÁÓˆÛË Î·È ÙËÓ ÚfiÏË„Ë Ù˘ Èı·Ó‹˜ ÓfiÛÔ˘. ∏ ‰È·Ù‡ˆÛË ÙˆÓ ÂÚˆÙËÌ¿ÙˆÓ ·˘ÙÒÓ Á›ÓÂÙ·È ÌÂ Û˘ÁÎÂÎÚÈ̤ÓÔ ÙÚfiÔ Î·È ·ÔÙÂÏÂ›Ù·È ·fi Ù· ÂÍ‹˜ Ù¤ÛÛÂÚ· ̤ÚË: 1. √Ì¿‰· ÛÙfi¯Ô˜ (population): ÏËı˘ÛÌfi˜ ÌÂ Û˘ÁÎÂÎÚÈ̤ӷ ¯·Ú·ÎÙËÚÈÛÙÈο fiÌÔÈ· Ì ÙÔ˘ ·ÛıÂÓÔ‡˜, fiˆ˜ .¯. ʇÏÔ, ËÏÈΛ·, Û˘ÁÎÂÎÚÈ̤ÓË ·Ûı¤ÓÂÈ· Î.¿.

2. ¶·Ú¤Ì‚·ÛË/ ŒÎıÂÛË (intervention/ exposure): ηıÔÚ›˙ÂÙ·È ˆ˜ ·ÈÙÈÔÏÔÁ›·, ‰È¿ÁÓˆÛË, ıÂÚ·›·, ÚfiÁÓˆÛË, ÚfiÏË„Ë Î.¿.

3. √Ì¿‰· Û‡ÁÎÚÈÛ˘ (control group): fiÔ˘ Â›Ó·È ÂÊ·ÚÌfiÛÈÌÔ .¯. ıÂÚ·›· placebo, ÂÓ·ÏÏ·ÎÙÈÎfi ‰È·ÁÓˆÛÙÈÎfi test Î.Ï.

4. ∫ÏÈÓÈ΋ ¤Î‚·ÛË (outcome): Â›Ó·È ÙÔ ˙ËÙÔ‡ÌÂÓÔ ÌÂÙ¿ ÙËÓ ·Ú¤Ì‚·ÛË/¤ÎıÂÛË Ô˘ ı· Â¤ÏıÂÈ Î·È ı· ÂËÚ¿ÛÂÈ ÙËÓ ÎÏÈÓÈ΋ ·fiÊ·ÛË .¯. ‚ÂÏÙ›ˆÛË ˘Á›·˜, ÚfiÏË„Ë ·Ûı¤ÓÂÈ·˜,

249

π·ÙÚÈ΋ ‚·ÛÈṲ̂ÓË ÛÙȘ ÂӉ›ÍÂȘ

·ÔÊ˘Á‹ ÂÈÏÔÎÒÓ, ÈηÓfiÙËÙ· ÂÓfi˜ ̤ÛÔ˘ Ó· ÂȂ‚·ÈÒÓÂÈ ÌÈ· ·Ûı¤ÓÂÈ· Î.¿. (5). °È· Ó· Á›ÓÂÈ ÈÔ Î·Ù·ÓÔËÙ‹ Ë ‰È·‰Èηۛ· πµ∂, ·Ú·ı¤ÙÔ˘Ì ٷ ·Ú·Î¿Ùˆ ·Ú·‰Â›ÁÌ·Ù·, Ù· ÔÔ›· Ê·›ÓÔÓÙ·È Û˘ÓÔÙÈο ÛÙÔÓ ¶›Ó·Î· 2: ¶·Ú¿‰ÂÈÁÌ· 1: ∞ÁfiÚÈ 3 ÂÙÒÓ, Ì ÂχıÂÚÔ ·ÙÔÌÈÎfi ·Ó·ÌÓËÛÙÈÎfi, ÚÔÛ¤Ú¯ÂÙ·È ÛÙÔ Â͈ÙÂÚÈÎfi ·È‰È·ÙÚÈÎfi È·ÙÚÂ›Ô ÂÂÈÁfiÓÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ Ì ˘ÚÂÙfi ¤ˆ˜ 38ÆC, ÚÈÓ›Ùȉ·, ‚‹¯· Î·È ¤ÓÙÔÓË ˆÙ·ÏÁ›·. ∏ ÎÏÈÓÈ΋ ÂͤٷÛË ·ÔηχÙÂÈ ÔÍ›· ̤ÛË ˆÙ›Ùȉ· (√ªø). ∆Ô ÂÚÒÙËÌ· Ô˘ ·Ó·‰‡ÂÙ·È ‰È·Ù˘ÒÓÂÙ·È, Ì ‚¿ÛË Ù· ·Ú·¿Óˆ, ˆ˜ ÂÍ‹˜: ñ (ÏËı˘ÛÌfi˜) ·È‰È¿ ÚÔÛ¯ÔÏÈ΋˜ ËÏÈΛ·˜ Ì √ªø ñ (·Ú¤Ì‚·ÛË) ¯ÔÚ‹ÁËÛË ·ÓÙÈ‚ÈÔÙÈ΋˜ ·ÁˆÁ‹˜ ñ (ÔÌ¿‰· Û‡ÁÎÚÈÛ˘) ÌË ¯ÔÚ‹ÁËÛË ·ÓÙÈ‚ÈÔÙÈ΋˜ ·ÁˆÁ‹˜ ñ (ÎÏÈÓÈ΋ ¤Î‚·ÛË) ‡ÊÂÛË ˆÙ·ÏÁ›·˜ - ·ÔÊ˘Á‹ ÂÈÏÔÎÒÓ √ªø - ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ·ÓÙÈ‚ÈÔÙÈÎÒÓ Î.Ï. ñ ‰È·Ù‡ˆÛË, ÏÔÈfiÓ, ÙÔ˘ ÂÚˆÙ‹Ì·ÙÔ˜: “ÃÚ‹˙ÂÈ ·ÓÙÈ‚›ˆÛ˘ ¤Ó· ·È‰› Ì √ªø;” ÌÂÙ·ÙÚ¤ÂÙ·È Û‡Ìʈӷ Ì ٷ ·Ú·¿Óˆ: “™Â ·È‰È¿ ÚÔÛ¯ÔÏÈ΋˜ ËÏÈΛ·˜ Ì √ªø (ÏËı˘ÛÌfi˜), Â›Ó·È ‰˘Ó·ÙfiÓ Ë ¯ÔÚ‹ÁËÛË ·ÓÙÈ‚ÈÔÙÈÎÔ‡ (·Ú¤Ì‚·ÛË) -Û ۯ¤ÛË Ì ÙË ÌË ¯ÔÚ‹ÁËÛË ·ÓÙÈ‚ÈÔÙÈÎÔ‡ (ÔÌ¿‰· Û‡ÁÎÚÈÛ˘)- Ó· ·Ì‚χÓÂÈ Ù· Û˘ÌÙÒÌ·Ù· Ù˘ ˆÙ·ÏÁ›·˜, ÙÔ˘ ˘ÚÂÙÔ‡ Î·È Ù˘ ÚÈÓ›Ùȉ·˜; Ó· ÌÂÈÒÛÂÈ ÙÔ ÔÛÔÛÙfi ÙˆÓ ÂÈÏÔÎÒÓ √ªø, fiˆ˜ ÎÒʈÛË, ÌËÓÈÁÁ›Ùȉ· ‹ Ì·ÛÙÔÂȉ›Ùȉ·; Ó· ÂÈ‚·Ú‡ÓÂÈ ÙÔÓ ·ÛıÂÓ‹ ÏfiÁˆ ÙˆÓ ·ÓÂÈı‡ÌËÙˆÓ ÂÓÂÚÁÂÈÒÓ ÙˆÓ ·ÓÙÈ‚ÈÔÙÈÎÒÓ (ÎÏÈÓÈ΋ ¤Î‚·ÛË);” (6). ¶·Ú¿‰ÂÈÁÌ· 2: ∆Ô ÎÏÈÓÈÎfi ÂÚÒÙËÌ· “¯ÚÂÈ¿˙ÂÙ·È Ó· ÓÔÛËχԢÌ ·È‰È¿ Ì ÂÂÈÛfi‰ÈÔ ·ÏÒÓ ˘ÚÂÙÈÎÒÓ Û·ÛÌÒÓ;” ‰È·Ù˘ÒÓÂÙ·È,

Û‡Ìʈӷ Ì ٷ ·Ú·¿Óˆ, ˆ˜ ÂÍ‹˜: “™Â ·È‰È¿ 0-6 ÂÙÒÓ Ì ·ÏÔ‡˜ ˘ÚÂÙÈÎÔ‡˜ Û·ÛÌÔ‡˜ (ÏËı˘ÛÌfi˜), Ë 24ˆÚË ÓÔÛËÏ›· (·Ú¤Ì‚·ÛË) Û ۇÁÎÚÈÛË Ì ÙËÓ 6ˆÚË ·Ú·ÎÔÏÔ‡ıËÛË (ÔÌ¿‰· Û‡ÁÎÚÈÛ˘), ÌÂÈÒÓÂÈ ÙËÓ Èı·ÓfiÙËÙ· ˘ÔÙÚÔ‹˜ ÙˆÓ ˘ÚÂÙÈÎÒÓ Û·ÛÌÒÓ (·ÔÙ¤ÏÂÛÌ·);” ¶·Ú¿‰ÂÈÁÌ· 3: ∆Ô ÎÏÈÓÈÎfi ÂÚÒÙËÌ· “¶Ú¤ÂÈ Ó· ÂÌ‚ÔÏÈ¿˙ÔÓÙ·È Ù· ‚Ú¤ÊË Ì ÙÔ ÂÌ‚fiÏÈÔ ÙÔ˘ ÎÔηÙË;” ÌÂÙ·ÙÚ¤ÂÙ·È ÛÙÔ ÂÍ‹˜: “™Â ‚Ú¤ÊË 2 ÌËÓÒÓ (ÏËı˘ÛÌfi˜), Ô ÂÌ‚ÔÏÈ·ÛÌfi˜ Ì ÙÔ ÂÌ‚fiÏÈÔ ÙÔ˘ ÎÔηÙË (·Ú¤Ì‚·ÛË), Û ۇÁÎÚÈÛË Ì ηıfiÏÔ˘ ÂÌ‚ÔÏÈ·ÛÌfi (ÔÌ¿‰· Û‡ÁÎÚÈÛ˘), ÌÂÈÒÓÂÈ ÙË ÓÔÛËÚfiÙËÙ· Ù˘ ÓfiÛÔ˘ ÙÔ˘ ÎÔηÙË; ·˘Í¿ÓÂÈ ÙË ÓÔÛËÚfiÙËÙ· Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ÂÌ‚fiÏÈÔ; (·ÔÙ¤ÏÂÛÌ· Ô˘ ·Ó·˙ËÙÔ‡ÌÂ)”. ªÈ· Ù¤ÙÔÈ· ‰È¿ÚıÚˆÛË ÙÔ˘ ÎÏÈÓÈÎÔ‡ ÚÔ‚Ï‹Ì·ÙÔ˜ ÛÎÔfi ¤¯ÂÈ Ó· ÂÛÙÈ¿ÛÂÈ ÙËÓ ¤Ú¢ӷ ÙÔ˘ È·ÙÚÔ‡ ÛÂ Û˘ÁÎÂÎÚÈ̤ӷ ÂÚˆÙ‹Ì·Ù· Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌËÓ ÂÏ·ÁÔ‰ÚÔÌ› ̤۷ ÛÙÔ ¯¿Ô˜ Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜. ™Â ·ÓÙ›ıÂÙË ÂÚ›ÙˆÛË, ÌÈ· ·ÓÂ·ÚÎÒ˜ ÂÛÙÈ·Ṳ̂ÓË ÂÚÒÙËÛË ı· Ô‰ËÁ‹ÛÂÈ ÛÙËÓ ·Û¿ÊÂÈ·.

∞Ó·˙‹ÙËÛË Î·Ù¿ÏÏËÏˆÓ ÂӉ›ÍÂˆÓ ™ÙË ‚È‚ÏÈÔÁÚ·Ê›· ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÌÂϤÙ˜ Û¯ÂÙÈο Ì ÙË ‰È¿ÁÓˆÛË, ÙËÓ ÚfiÁÓˆÛË, ÙËÓ ·ÈÙÈÔÏÔÁ›· Î·È ÙË ıÂÚ·›·, ı¤Ì·Ù· ‰ËÏ·‰‹ Ô˘ ηıËÌÂÚÈÓ¿ ··Û¯ÔÏÔ‡Ó ÙÔ˘˜ ÎÏÈÓÈÎÔ‡˜ È·ÙÚÔ‡˜. ∞Ó¿ÏÔÁ· Ì ÙÔÓ Ù‡Ô ÙÔ˘ ÎÏÈÓÈÎÔ‡ ÂÚˆÙ‹Ì·ÙÔ˜ ·Ó·˙ËÙÔ‡ÌÂ Î·È ÙËÓ ·ÓÙ›ÛÙÔȯ· ۯ‰ȷṲ̂ÓË ÌÂϤÙË (¶›Ó·Î·˜ 3). ∂¿Ó, ÁÈ· ·Ú¿‰ÂÈÁÌ·, ÙÔ ÎÏÈÓÈÎfi ÂÚÒÙËÌ· ·ÊÔÚ¿ ıÂÚ·›· ÌÈ·˜ ÓfiÛÔ˘, ÙfiÙ ·Ó·˙ËÙÔ‡ÌÂ Ù˘¯·ÈÔÔÈË̤Ó˜ ÂÏÂÁ¯fiÌÂÓ˜ ÌÂϤÙ˜ (Randomized Control Trials - RCTs) Ô˘ ·ÔÙÂÏÔ‡Ó ÚfiÙ˘Ô

¶›Ó·Î·˜ 2. ¶·Ú·‰Â›ÁÌ·Ù· ‰È·Ù‡ˆÛ˘ ÎÏÈÓÈÎÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ πµE OÌ¿‰· ÛÙfi¯Ô˜/ ¶ÏËı˘ÛÌfi˜

¶·Ú¤Ì‚·ÛË/ ¤ÎıÂÛË

√Ì¿‰· Û‡ÁÎÚÈÛ˘

ŒÎ‚·ÛË

¶·È‰È¿ ÚÔÛ¯ÔÏÈ΋˜ ËÏÈΛ·˜ Ì √ªø

ÃÔÚ‹ÁËÛË ·ÓÙÈ‚ÈÔÙÈÎÒÓ

ªË ¯ÔÚ‹ÁËÛË ·ÓÙÈ‚ÈÔÙÈÎÒÓ

¶·È‰È¿ 0-6 ÂÙÒÓ Ì ·ÏÔ‡˜ ˘ÚÂÙÈÎÔ‡˜ Û·ÛÌÔ‡˜ µÚ¤ÊË 2 ÌËÓÒÓ

24ˆÚË ÓÔÛËÏ›·

6ˆÚË ·Ú·ÎÔÏÔ‡ıËÛË

ñ ⁄ÊÂÛË Û˘ÌÙˆÌ¿ÙˆÓ √ªø (˘ÚÂÙfi˜, ˆÙ·ÏÁ›· Î.Ï.) ñ ∞ÔÊ˘Á‹ ÂÈÏÔÎÒÓ √ªø (Ì·ÛÙÔÂȉ›Ùȉ·, ÎÒʈÛË Î.Ï.) ªÂ›ˆÛË Èı·ÓfiÙËÙ·˜ ˘ÔÙÚÔ‹˜ Û·ÛÌÒÓ

∂Ì‚ÔÏÈ·ÛÌfi˜ ¤Ó·ÓÙÈ ÙÔ˘ ÎÔηÙË

∫·ıfiÏÔ˘ ÂÌ‚ÔÏÈ·ÛÌfi˜ ¤Ó·ÓÙÈ ÎÔηÙË

ñ ¡ÔÛËÚfiÙËÙ· Û¯ÂÙÈ˙fiÌÂÓË Ì ÙË ÓfiÛÔ ÙÔ˘ ÎÔηÙË ñ ¡ÔÛËÚfiÙËÙ· Û¯ÂÙÈ˙fiÌÂÓË Ì ÙÔ ÂÌ‚fiÏÈÔ ÙÔ˘ ÎÔηÙË ¶·È‰È·ÙÚÈ΋ 2006;69:247-254

250

™. ∏Ï›·, µ. ∞ÁÁÂÏ¿ÎÔ˘

›‰Ô˜ ¤Ú¢ӷ˜ ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ıÂÚ·¢ÙÈÎÒÓ Ì¤ÛˆÓ. ¶Ôχ ÂÚÈÛÛfiÙÂÚÔ ·Ó·˙ËÙÔ‡ÌÂ Û˘ÛÙËÌ·ÙÈΤ˜ ·Ó·ÛÎÔ‹ÛÂȘ ·˘ÙÒÓ ÙˆÓ ÌÂÏÂÙÒÓ Ì Èı·Ó‹ ÌÂÙ·-·Ó¿Ï˘ÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ (Systematic Review (SR) of RCTs - Meta-analyses of SR of RCTs) Ô˘ Â›Ó·È ·ÎfiÌ· ¤Ó· ‚‹Ì· ÈÔ ¤Ú·, ·ÊÔ‡ Ù· ·ÔÙÂϤÛÌ·Ù· ÔÏÏ·ÏÒÓ Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ÌÂÏÂÙÒÓ Û˘Ó‰˘¿˙ÔÓÙ·È ÌÂٷ͇ ÙÔ˘˜ Î·È ·ÔÚÚ¤Ô˘Ó Û˘ÁÎÂÓÙÚˆÙÈο ·ÔÙÂϤÛÌ·Ù·. °È· ÙÔ˘˜ ˘fiÏÔÈÔ˘˜ Ù‡Ô˘˜ ÎÏÈÓÈÎÒÓ ÂÚˆÙËÌ¿ÙˆÓ ·Ú·¤ÌÔ˘Ì ÛÙÔÓ ¶›Ó·Î· 3. ∂›Ó·È, ÏÔÈfiÓ, Ôχ ÛËÌ·ÓÙÈÎfi Ó· ÁÓˆÚ›˙Ô˘Ì ÂÍ·Ú¯‹˜ ÙÔ Â›‰Ô˜ Ù˘ ÌÂϤÙ˘ Ô˘ ·ÓÙÈÛÙÔȯ› ÛÙÔÓ Ù‡Ô ÙÔ˘ ÂÚˆÙ‹Ì·Ùfi˜ Ì·˜ (‰È¿ÁÓˆÛË - ·ÈÙÈÔÏÔÁ›· - ıÂÚ·›· - ÚfiÁÓˆÛË), ·ÊÔ‡ ¤ÙÛÈ ÂÍ·ÛÊ·Ï›˙Ô˘Ì ηٿ ÌÂÁ¿ÏÔ Ì¤ÚÔ˜ ÙËÓ ÂÁ΢ÚfiÙËÙ· Î·È ÙËÓ ·ÍÈÔÈÛÙ›· ÙˆÓ ÏËÚÔÊÔÚÈÒÓ Ô˘ ı· Û˘ÏϤÍÔ˘ÌÂ. √È ÎÏÈÓÈΤ˜, ÏÔÈfiÓ, ·ÔÊ¿ÛÂȘ ÔÊ›ÏÔ˘Ó Ó· ÛÙËÚ›˙ÔÓÙ·È Û ηϤ˜ ÂӉ›ÍÂȘ. ¶Èı·ÓfiÓ, Ë Ù¤ÏÂÈ· ÎÏÈÓÈ΋ ÌÂϤÙË ÁÈ· ¤Ó· ÎÏÈÓÈÎfi ı¤Ì· Ô˘ Ì·˜ ·ÊÔÚ¿ Ó· ÌËÓ ¤¯ÂÈ ·ÎfiÌ· ‰ËÌÔÛÈ¢Ù› ‹ Ó· ÌËÓ ¤¯ÂÈ Á›ÓÂÈ. ™ÎÔfi˜ Â›Ó·È Ë ·Ó‡ÚÂÛË ÙˆÓ Î·Ï‡ÙÂÚˆÓ ÙÚÂ¯Ô˘ÛÒÓ ÂӉ›ÍÂˆÓ (best current evidence) ÁÈ· ÙË Ï‹„Ë ÙˆÓ Î·Ù·ÏÏËÏfiÙÂÚˆÓ ÎÏÈÓÈÎÒÓ ·ÔÊ¿ÛÂˆÓ Ô˘ ·ÊÔÚÔ‡Ó ÙÔ˘˜ ·ÛıÂÓ›˜ Ì·˜ ÙË ‰Â‰Ô̤ÓË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹.

¶ËÁ¤˜ ÂӉ›ÍÂˆÓ ™Ù· Ï·›ÛÈ· ·Ó·˙‹ÙËÛ˘ ··ÓÙ‹ÛÂˆÓ ÛÙȘ ηıËÌÂÚÈÓ¤˜ ÎÏÈÓÈΤ˜ ·Ôڛ˜ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ·Ó·ÁÓˆÚÈṲ̂ӷ È·ÙÚÈο ÂÁ¯ÂÈÚ›‰È· Î·È ‚È‚Ï›·, Ô˘ Û˘Ó‹ıˆ˜ ‚Ú›ÛÎÔÓÙ·È ÛÙËÓ ÚÔÛˆÈ΋ ‚È‚ÏÈÔı‹ÎË ÙÔ˘ οı ȷÙÚÔ‡. ÷ڷÎÙËÚÈÛÙÈο ·Ú·‰Â›ÁÌ·Ù· ›ӷÈ: ÙÔ Nelson-Textbook of ¶›Ó·Î·˜ 3. ∞ÓÙÈÛÙÔȯ›· ÎÏÈÓÈÎÔ‡ ÂÚˆÙ‹Ì·ÙÔ˜ Ì ›‰Ô˜ ÎÏÈÓÈ΋˜ ÌÂϤÙ˘ £ÂÚ·›· ñ ∆˘¯·ÈÔÔÈË̤Ó˜ ÂÏÂÁ¯fiÌÂÓ˜ ÌÂϤÙ˜ (∆∂ª) (Randomised Control Trials (RCTs)) ñ ™˘ÛÙËÌ·ÙÈ΋ ·Ó·ÛÎfiËÛË ∆∂ª ñ ªÂÙ·-·Ó¿Ï˘ÛË Û˘ÛÙËÌ·ÙÈÎÒÓ ·Ó·ÛÎÔ‹ÛÂˆÓ ∆∂ª ¢È¿ÁÓˆÛË (screening) ñ ™˘Á¯ÚÔÓÈΤ˜ ÌÂϤÙ˜ (cross-sectional studies) ñ ™˘ÛÙËÌ·ÙÈ΋ ·Ó·ÛÎfiËÛË Û˘Á¯ÚÔÓÈÎÒÓ ÌÂÏÂÙÒÓ ∞ÈÙÈÔÏÔÁ›· ñ ªÂϤÙ˜ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ (case-control studies) ñ ¢È·¯ÚÔÓÈΤ˜ ÌÂϤÙ˜ (cohort studies) ¶ÚfiÁÓˆÛË ñ ¢È·¯ÚÔÓÈΤ˜ ÌÂϤÙ˜ (cohort studies) ¶·È‰È·ÙÚÈ΋ 2006;69:247-254

Pediatrics ÁÈ· ·È‰È·ÙÚÈο ı¤Ì·Ù·, ÙÔ Red Book ÁÈ· ÏÔÈÌÒ‰Ë ÓÔÛ‹Ì·Ù·, ÙÔ ∂ıÓÈÎfi ™˘ÓÙ·ÁÔÏfiÁÈÔ ÙÔ˘ ∂√º ÁÈ· Ê¿Ú̷η ÛÙË ¯ÒÚ· Ì·˜ Î.Ô.Î., ηıÒ˜ Î·È ÂÚÈÔ‰Èο ÂÈÛÙËÌÔÓÈÎÔ‡ ÂÚȯÔ̤ÓÔ˘, fiˆ˜, .¯. The Lancet. ∂›Û˘ ·ÚÎÂÙ¿ ·fi Ù· ÂÁ¯ÂÈÚ›‰È· Ô˘ ÚԷӷʤÚıËηÓ, ηıÒ˜ Î·È ¿ÏÏ·, ˘¿Ú¯Ô˘Ó Î·È Û ËÏÂÎÙÚÔÓÈΤ˜ ÂΉfiÛÂȘ ÛÙÔ ‰È·‰›ÎÙ˘Ô. ∂Ó‰ÂÈÎÙÈο ·Ó·Ê¤ÚÔÓÙ·È Nelson on-line, Harrison on-line, e-Medicine, Archives of Disease in Childhood, Pediatrics eedition Î.Ï., Ô˘ Û˘Ó¯Ҙ ‰›‰Ô˘Ó ÏËÚÔÊÔڛ˜ Î·È Ì¿ÏÈÛÙ· ·Ó·ÓÂÒÓÔ˘Ó ÙÔ ˘ÏÈÎfi ÙÔ˘˜ Ôχ ÈÔ ¿ÌÂÛ· ·fi ÙȘ ÁÚ·Ù¤˜ ÂΉfiÛÂȘ. ª›· ¿ÏÏË ËÁ‹ ÏËÚÔÊÔÚÈÒÓ Â›Ó·È ÔÈ ËÏÂÎÙÚÔÓÈΤ˜ ‚¿ÛÂȘ ‰Â‰ÔÌ¤ÓˆÓ (electronic databases), ÔÈ Ôԛ˜ ‰È·ÎÚ›ÓÔÓÙ·È Û ‰‡Ô ηÙËÁÔڛ˜: ·) ‚¿ÛÂȘ ‰Â‰ÔÌ¤ÓˆÓ ¯ˆÚ›˜ Ê›ÏÙÚÔ. ÷ڷÎÙËÚÈÛÙÈÎfi ·Ú¿‰ÂÈÁÌ· ·˘Ù‹˜ Ù˘ ηÙËÁÔÚ›·˜ Â›Ó·È ÙÔ Û‡ÛÙËÌ· MEDLINE, ÙÔ ÔÔ›Ô Û˘ÓÙ¿ÛÛÂÙ·È ·fi ÙËÓ National Library of Medicine ÙˆÓ ∏ÓˆÌ¤ÓˆÓ ¶ÔÏÈÙÂÈÒÓ. ªÔÚԇ̠ӷ Ê·ÓÙ·ÛÙԇ̠ÌÈ· ÙÂÚ¿ÛÙÈ· ‚È‚ÏÈÔı‹ÎË Ì ·Ì¤ÙÚËÙ· Ú¿ÊÈ· fiÔ˘ ˘¿Ú¯Ô˘Ó ¿ÚıÚ· È·ÙÚÈÎÔ‡ ÂÚȯÔ̤ÓÔ˘ ÂÚÈÛÛfiÙÂÚ· ·fi 2.000.000 Û ·ÚÈıÌfi Î·È ÚÔ¤Ú¯ÔÓÙ·È ·fi ¿Óˆ ·fi 70 ¯ÒÚ˜, fiÔ˘ Û˘Ó¯Ҙ ·Ú¯ÂÈÔıÂÙÔ‡ÓÙ·È Ó¤· (ÂÚ›Ô˘ 1.000) ¿ÚıÚ· ËÌÂÚËÛ›ˆ˜. ∞˘Ù‹ Ë ËÏÂÎÙÚÔÓÈ΋ ‚È‚ÏÈÔı‹ÎË Â›Ó·È Â‡ÎÔÏ· Î·È ‰ˆÚÂ¿Ó ÚÔÛ‚¿ÛÈÌË Ì¤Ûˆ ÙÔ˘ ¢È·‰ÈÎÙ‡Ô˘ (http://www.ncbi.nlm.nih. gov/PubMed/). TÔ Û‡ÛÙËÌ· Medline Â›Ó·È Ì›· ·fi ÙȘ ÂÚ›Ô˘ 40 Ù¤ÙÔȘ ËÏÂÎÙÚÔÓÈΤ˜ ‚¿ÛÂȘ ‰Â‰ÔÌ¤ÓˆÓ fiÔ˘ ηٷ¯ˆÚÂ›Ù·È -¯ˆÚ›˜ fï˜ Ó· ·ÍÈÔÏÔÁÂ›Ù·È ÙÔ ÂÚȯfiÌÂÓfi ÙÔ˘˜ (¯ˆÚ›˜ Ê›ÏÙÚÔ)- ¤Ó·˜ ÁÈÁ·ÓÙÈ·›Ô˜ ·ÚÈıÌfi˜ ÂÈÛÙËÌÔÓÈÎÒÓ ¿ÚıÚˆÓ, fiÔ˘ Ô ·Ó·ÁÓÒÛÙ˘ ηÏÂ›Ù·È Ó· ·ÔÙÈÌ‹ÛÂÈ ÙËÓ ÔÈfiÙËÙ· ÙˆÓ ÏËÚÔÊÔÚÈÒÓ Ô˘ Ï·Ì‚¿ÓÂÈ (7). ‚) ‚¿ÛÂȘ ‰Â‰ÔÌ¤ÓˆÓ Ì ʛÏÙÚÔ. ™ÙËÓ Î·ÙËÁÔÚ›· ·˘Ù‹ ÔÈ ÌÂϤÙ˜ Ô˘ ÚÔÛʤÚÔÓÙ·È ÛÙÔÓ ¯Ú‹ÛÙË ¤¯Ô˘Ó ‹‰Ë ˘ÔÛÙ› ·˘ÛÙËÚ‹ ·ÍÈÔÏfiÁËÛË. ∂ÈÙÚÔ¤˜ ·fi ÂÍÂȉÈÎÂ˘Ì¤ÓÔ˘˜ ÂÈÛÙ‹ÌÔÓ˜ Â¿Óˆ ÛÙÔÓ Û¯Â‰È·ÛÌfi ÂÚ¢ÓÒÓ ÂÍ·ÛÊ·Ï›˙Ô˘Ó ÙËÓ ·ÚÔ¯‹ ÏËÚÔÊÔÚÈÒÓ ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜, Ì ÌÂȈ̤ӷ Ù· ÂÚÈıÒÚÈ· ÌÂÚÔÏË„›·˜, ‚·ÛÈ˙fiÌÂÓ˜ ÛÙ· ηχÙÂÚ· ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ Ô˘ ¤¯ÂÈ Ó· ·Ó·‰Â›ÍÂÈ Ë ÙÚ¤¯Ô˘Û· ¤Ú¢ӷ. £· ÙÔÏÌÔ‡Û·Ì ӷ ԇ̠ˆ˜ ·ÔÙÂÏ› ÙÔ ›‰ÈÔ ÙÔ ‚‹Ì· 2 Ù˘ π·ÙÚÈ΋˜ µ·ÛÈṲ̂Ó˘ ÛÙȘ ∂Ӊ›ÍÂȘ (Evidence Based Medicine) (‚Ϥ ¶›Ó·Î· 1), fiÔ˘ οÔÈÔÈ ÙÚ›ÙÔÈ ¤¯Ô˘Ó οÓÂÈ ÙË ‰Ô˘ÏÂÈ¿ ÁÈ· Ì·˜ ÛÙË ‰È·‰Èηۛ· ·Ó·˙‹ÙËÛ˘ Î·È Û˘ÏÏÔÁ‹˜ ÙˆÓ Î·Ï‡ÙÂÚˆÓ ÂÈÛÙËÌÔÓÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ (best evidence). ¶·Ú·‰Â›ÁÌ·Ù·

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π·ÙÚÈ΋ ‚·ÛÈṲ̂ÓË ÛÙȘ ÂӉ›ÍÂȘ

Ù¤ÙÔÈˆÓ ËÁÒÓ ÂӉ›ÍÂˆÓ ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 4 (8). ∂›Û˘, Û ÔÚÈṲ̂ӷ ·ÓÂÈÛÙ‹ÌÈ·, ÙÌ‹Ì·Ù· È·ÙÚÈÎÒÓ Û¯ÔÏÒÓ ¤¯Ô˘Ó ·Û¯ÔÏËı› ÌÂ Û˘Ó‹ıË ÚÔ‚Ï‹Ì·Ù· Ô˘ ··ÓÙÒÓÙ·È ÛÙËÓ Î·ıËÌÂÚÈÓ‹ ÎÏÈÓÈ΋ Ú¿ÍË Î·È, ·ÎÔÏÔ˘ıÒÓÙ·˜ fiÏË ÙË ‰È·‰Èηۛ· πµ∂, ·Ô‰›‰Ô˘Ó ÌÈÎÚ¤˜, ηٷÓÔËÙ¤˜, ‡ÎÔÏ· ÂÊ·ÚÌfiÛÈ̘ ÂÚÈÏ‹„ÂȘ ÙˆÓ Î·Ï‡ÙÂÚˆÓ ÙÚÂ¯Ô˘ÛÒÓ ÂӉ›ÍˆÓ. ∆· ı¤Ì·Ù· ·˘Ù¿, Ô˘ ¤¯Ô˘Ó ‹‰Ë ÎÚÈÙÈο ÚÔ-·ÍÈÔÏÔÁËı› (Critically Appraised Topics - CATs), ·Ó¢ڛÛÎÔÓÙ·È ÛÙËÓ Â›ÛËÌË ÈÛÙÔÛÂÏ›‰· ÙÔ˘˜ (‚Ϥ ¶›Ó·Î· 4). ŒÂÈÙ· ·fi ÙËÓ ·ÍÈÔÏfiÁËÛË ÙˆÓ ‰Â‰Ô̤ӈÓ, ÔÈ ËÁ¤˜ Ì ʛÏÙÚÔ ·Ó·Ê¤ÚÔ˘Ó ÛÙÔ Ù¤ÏÔ˜ οÔȘ ˘ԉ›ÍÂȘ (recommendations), ÔÈ Ôԛ˜ Û˘Óԉ‡ÔÓÙ·È ·fi ·Ú·ÙËÚ‹ÛÂȘ ÁÈ· ÙÔ Â›Â‰Ô ·ÍÈÔÈÛÙ›·˜ Î·È ÔÈfiÙËÙ·˜ ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ô˘ Û˘Óı¤ÙÔ˘Ó ÙȘ ˘ԉ›ÍÂȘ ·˘Ù¤˜. ∆· Â›‰· ·˘Ù¿ ·Ó·Ê¤ÚÔÓÙ·È ˆ˜ ∞, µ, C Î·È D (Ï·ÙÈÓÈο ÁÚ¿ÌÌ·Ù·). °È· ÂÚÈÛÛfiÙÂÚ˜ ÏÂÙÔ̤ÚÂȘ ·Ú·¤ÌÔ˘Ì ÛÙÔÓ ¶›Ó·Î· 5 (9). ∞ÊÔ‡ Û˘ÓÙ¿ÍÔ˘Ì ÙËÓ ÂÚÒÙËÛ‹ Ì·˜, ÔÚ›˙Ô˘Ì ϤÍÂȘ ÎÏÂȉȿ Ô˘ ·ÊÔÚÔ‡Ó ¿ÌÂÛ· ÙÔ ÎÏÈÓÈÎfi Ì·˜ Úfi‚ÏËÌ·. ∏ οı ËÁ‹ ÏËÚÔÊÔÚÈÒÓ ÛÙÔ ¢È·‰›ÎÙ˘Ô ·Ú¤¯ÂÈ Â›Û˘, ¤Ó· ¢ÚÂÙ‹ÚÈÔ Ï¤ÍÂˆÓ ÁÈ· ÙË ‰È¢ÎfiÏ˘ÓÛË ÙÔ˘ ¯Ú‹ÛÙË, Ô˘ Û˘ÁÎÂÎÚÈ̤ӷ ÛÙÔ MEDLINE ÔÓÔÌ¿˙ÂÙ·È Medical Subject Headings (MeSH). °È· ·Ú¿‰ÂÈÁÌ· ·Ó ¯ÚËÛÈÌÔÔÈ‹ÛÔ˘Ì ÙËÓ ·ÁÁÏÈ΋ ϤÍË chickenpox (·ÓÂÌ¢ÏÔÁÈ¿), ÛÙÔ MeSH ·Ó·Ê¤ÚÂÙ·È Î·È ˆ˜ Varicella Zoster. ŒÙÛÈ, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙȘ ‰ÈΤ˜ Ì·˜ ϤÍÂȘ ·Ó·˙‹ÙËÛ˘, ηıÒ˜ Î·È ÙȘ ϤÍÂȘ ÙÔ˘ ¢ÚÂÙËÚ›Ô˘ (MeSH), ‚ÂÏÙÈÒÓÔ˘Ì ÙËÓ Â˘·ÈÛıËÛ›· Ù˘ ¤ÚÂ˘Ó¿˜ Ì·˜ Î·È ÂÍ·ÛÊ·Ï›˙Ô˘Ì ÙËÓ ·Ó¿ÎÙËÛË fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ÂÚÈÛÛfiÙÂÚˆÓ Û¯ÂÙÈÎÒÓ ¿ÚıÚˆÓ. ŒÂÈÙ· ı¤ÙÔ˘Ì οÔÈÔ˘˜ ÂÚÈÔÚÈÛÌÔ‡˜ (limits) ÛÙËÓ ¤ÚÂ˘Ó¿ Ì·˜, fiˆ˜ .¯. Ù· ¿ÚıÚ· Ô˘ ı· ·ÓÂ-

‚ÚÂıÔ‡Ó Ó· ·ÊÔÚÔ‡Ó Û ·ÓıÚÒÔ˘˜ Î·È fi¯È ˙Ò·, ËÏÈΛ· ÏËı˘ÛÌÔ‡ .¯. ·È‰È·ÙÚÈÎfi˜ ÏËı˘ÛÌfi˜, ÁÏÒÛÛ· ¿ÚıÚÔ˘ .¯. Ó· Â›Ó·È ÌfiÓÔ ∞ÁÁÏÈο, ›‰Ô˜ ¤Ú¢ӷ˜, Ì ‚¿ÛË ·Ó ÙÔ ÎÏÈÓÈÎfi Ì·˜ ı¤Ì· ·ÊÔÚ¿ ıÂÚ·›·, ÚfiÁÓˆÛË Î.Ï., .¯. Meta-analyses of Systematic Reviews, Cohort studies ·ÓÙ›ÛÙÔȯ·, Î.Ô.Î. (10). ŒÓ·˜ ÔÏ˘¿Û¯ÔÏÔ˜ ÎÏÈÓÈÎfi˜ È·ÙÚfi˜ ‰ÂÓ Â›Ó·È ¿ÓÙÔÙ Û ı¤ÛË Ó· ·ÍÈÔÏÔÁ‹ÛÂÈ ÙËÓ ÂÁ΢ÚfiÙËÙ· ÙˆÓ ÏËÚÔÊÔÚÈÒÓ Ô˘ ·Ó¢ڛÛÎÂÈ, ›Ù ÏfiÁˆ ¤ÏÏÂȄ˘ ¯ÚfiÓÔ˘ ›Ù ÏfiÁˆ ¤ÏÏÂȄ˘ ÁÓÒÛÂˆÓ ÛÙ·ÙÈÛÙÈ΋˜ ‹ ·ÎfiÌ·, ÏfiÁˆ ÂÚÈÔÚÈṲ̂Ó˘ ÚfiÛ‚·Û˘ ÛÙo ¢È·‰›ÎÙ˘Ô. ∫·Ï‡ÙÂÚÔ, ÏÔÈfiÓ, Â›Ó·È Ó· ÍÂÎÈÓ¿ ÙËÓ ¤Ú¢ӷ ·fi ÙȘ ËÁ¤˜ ÂΛӘ Ô˘ ÚÔÛʤÚÔ˘Ó ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜ ÏËÚÔÊÔڛ˜, ÙȘ ÚÔ·Ó·ÊÂÚı›Û˜ ‚¿ÛÂȘ ‰Â‰ÔÌ¤ÓˆÓ Ì ʛÏÙÚÔ, fiˆ˜ Cochrane Library, Clinical Evidence, UpToDate, CATs Î.Ï. ∂¿Ó ·˘Ù¤˜ ÔÈ ËÁ¤˜ ‰ÂÓ ·Ô‰ÒÛÔ˘Ó Î¿ÔȘ ¯Ú‹ÛÈ̘ ÏËÚÔÊÔڛ˜ ‹, ÂÂȉ‹ Û οÔȘ ··ÈÙÂ›Ù·È Û˘Ó‰ÚÔÌ‹, ‰ÂÓ Â›Ó·È ‰˘Ó·Ù‹ Ë ÚfiÛ‚·ÛË, ÙfiÙ ÚÔ¯ˆÚԇ̠ÛÙȘ ËÁ¤˜ ¯ˆÚ›˜ Ê›ÏÙÚÔ, fiˆ˜ .¯. ÙË MEDLINE.

∞ÍÈÔÏfiÁËÛË ‰Â‰ÔÌ¤ÓˆÓ ªÂÙ¿ ÙË Û˘ÏÏÔÁ‹ fiÏˆÓ ÙˆÓ ÂӉ›ÍÂˆÓ Ì¤Ûˆ ÙˆÓ ËÁÒÓ Ô˘ ÚԷӷʤÚıËηÓ, ÙÔ ÂfiÌÂÓÔ ‚‹Ì· Â›Ó·È Ë ÎÚÈÙÈ΋ ·ÍÈÔÏfiÁËÛË (critical appraisal) Ù˘ ·ÍÈÔÈÛÙ›·˜ ÙˆÓ ÏËÚÔÊÔÚÈÒÓ ·˘ÙÒÓ, ÒÛÙ ӷ ·Ô‰Âȯı› Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È Ë Â¿ÚÎÂÈ¿ ÙÔ˘˜ ÛÙËÓ ·Ó·˙‹ÙËÛË ÙÚfiˆÓ ‚ÂÏÙ›ˆÛ˘ Ù˘ ÊÚÔÓÙ›‰·˜ ÙÔ˘ ·ÛıÂÓÔ‡˜. ™ËÌ·ÓÙÈÎfi Â›Ó·È ÛÙÔ Â›Â‰Ô ·˘Ùfi Ó· Á›ÓÂÈ Î·Ù·ÓÔËÙ‹ Ë ‰È·ÊÔÚ¿ ÌÂٷ͇ ÎÚÈÙÈ΋˜ ·ÍÈÔÏfiÁËÛ˘ Ì›·˜ ÎÏÈÓÈ΋˜ ÌÂϤÙ˘ Î·È ·Ï¿ ·Ó¿ÁÓˆÛ‹˜ Ù˘, ·ÊÔ‡ ÔÔÈÔÛ‰‹ÔÙ ÌÔÚ› Ó· ‰ËÌÔÛȇÛÂÈ ÔÙȉ‹ÔÙ ÛÙÔ ¢È·‰›ÎÙ˘Ô. ŒÙÛÈ ·ÍÈÔÏÔÁÔ‡ÌÂ:

¶›Ó·Î·˜ 4. µ¿ÛÂȘ ‰Â‰ÔÌ¤ÓˆÓ (databases) µ¿ÛÂȘ ‰Â‰Ô̤ӈÓ

πÛÙÔÛÂÏ›‰·

The Cochrane Collaboration Database of Abstracts of Reviews of Effects Clinical Evidence TRIP (Turning Research into Practice) UpToDate ACP Journal Club Evidence-based Medicine Reviews (OVID) MEDLINE (PubMed) CATs - University of Michigan, USA CATs - University of North Carolina, USA CATs - University of Manchester, UK

http://www.thecochranelibrary.com http://www.york.ac.uk/inst/crd/ http://www.clinicalevidence.org http://www.tripdatabase.com http://www.uptodate.com http://acpjc.org http://www.ovid.com http://www.ncbi.nlm.nih.gov/PubMed/ http://www.med.umich.edu/pediatrics/ebm/ http://www.med.unc.edu/medicine/edusrc/ http://www.bestbets.org ¶·È‰È·ÙÚÈ΋ 2006;69:247-254

252

™. ∏Ï›·, µ. ∞ÁÁÂÏ¿ÎÔ˘

¶›Ó·Î·˜ 5. ∂›Â‰Ô ÂӉ›ÍÂˆÓ (levels of evidence) Î·È Â›Â‰Ô Û˘ÛÙ¿ÛÂˆÓ (recommendation grades) ∂›Â‰Ô (level) ∂Ӊ›ÍÂȘ Û˘ÛÙ¿ÛˆÓ

∂ÚÌËÓ›·

A

∆Ô˘Ï¿¯ÈÛÙÔÓ Ì›· ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜ ÌÂÙ·-·Ó¿Ï˘ÛË (ª∞) ‹ Û˘ÛÙËÌ·ÙÈ΋ ·Ó·ÛÎfiËÛË (™∞) ‹ ™∞ ∆∂ª ‹ Ù˘¯·ÈÔÔÈË̤ÓË ÂÏÂÁ¯fiÌÂÓË ÌÂϤÙË (∆∂ª) Ì Ôχ ÌÈÎÚfi ΛӉ˘ÓÔ ÛÊ¿ÏÌ·ÙÔ˜ Ì ·ÔÙÂϤÛÌ·Ù· ¿ÌÂÛ· ÂÊ·ÚÌfiÛÈÌ· ÛÙÔÓ ÏËı˘ÛÌfi-ÛÙfi¯Ô Î·È ·Ú·Ï‹ÛÈ· ÌÂٷ͇ ÙˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ.

À„ËÏ‹˜ ÔÈfiÙËÙ·˜ ÂӉ›ÍÂȘ ¿ÓÙ· ·Ô‰ÂÎÙ¤˜ Û˘ÛÙ¿ÛÂȘ, ·ԉ‰ÂÈÁ̤ӷ ·ÛÊ·Ï›˜, ·Ó·ÌÊ›‚ÔÏ· ¯Ú‹ÛÈ̘

B

À„ËÏ‹˜ ÔÈfiÙËÙ·˜ ÌÂϤÙ˜ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ (case-control studies) ‹ ‰È·¯ÚÔÓÈΤ˜ (cohort studies) ‹ ™∞ ·˘ÙÒÓ, Ì ÌÈÎÚfi ΛӉ˘ÓÔ ‡·Ú͢ Û˘Á¯˘ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, Ù˘¯·›Ô˘ ‹ ÛÊ¿ÏÌ·ÙÔ˜, Ì ÌÂÁ¿ÏË Èı·ÓfiÙËÙ· Ë Û¯¤ÛË Ô˘ ÌÂÏÂÙ¿Ù·È Ó· Â›Ó·È ·ÈÙÈÔÏÔÁÈ΋ Î·È ¿ÌÂÛ· ÂÊ·ÚÌfiÛÈÌË ÛÙÔÓ ÏËı˘ÛÌfi-ÛÙfi¯Ô ÂȉÂÈÎÓ‡ÔÓÙ·˜ ·ÔÙÂϤÛÌ·Ù· ·Ú·Ï‹ÛÈ· ÌÂٷ͇ ÙˆÓ ÌÂÏÂÙÒÓ ‹ Û˘ÁÎÂÓÙÚˆÙÈο ·ÔÙÂϤÛÌ·Ù· ·fi ÙÔ˘Ï¿¯ÈÛÙÔÓ Ì›· ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜ ª∞, ™∞, ‹ ™∞ ∆∂ª ‹ ∆∂ª Ì ÌÈÎÚfi ΛӉ˘ÓÔ ÛÊ¿ÏÌ·ÙÔ˜ ‹ Û‡ÓÔÏÔ ÂӉ›ÍÂˆÓ ·fi ÌÂϤÙ˜ Ì ÌÈÎÚfi ΛӉ˘ÓÔ ÛÊ¿ÏÌ·ÙÔ˜ Ô˘ Ó· ÂȉÂÈÎÓ‡Ô˘Ó ·Ú·Ï‹ÛÈ· ·ÔÙÂϤÛÌ·Ù·.

Ÿ¯È ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜ ÂӉ›ÍÂȘ ·Ô‰ÂÎÙ¤˜ Û˘ÛÙ¿ÛÂȘ, ·ÛÊ·Ï›˜, ¯Ú‹ÛÈ̘ (¯Ú‹ÛË ÙˆÓ Ì¤¯ÚÈ ÙÒÚ· Û˘ÛÙ¿ÛˆÓ/Ô‰ËÁÈÒÓ ‹ ¯Ú‹ÛË ÙˆÓ Ó¤ˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ¤Ú¢ӷ˜)

C

™‡ÓÔÏÔ ÂӉ›ÍÂˆÓ ·fi ηÏÔۯ‰ȷṲ̂Ó˜ ÌÂϤÙ˜ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ ‹ ‰È·¯ÚÔÓÈÎÒÓ ÌÂÏÂÙÒÓ Ì ÌÈÎÚfi ΛӉ˘ÓÔ ‡·Ú͢ ·Ú·ÁfiÓÙˆÓ Û‡Á¯˘Û˘, Ù˘¯·›Ô˘ ‹ ÛÊ¿ÏÌ·ÙÔ˜ Î·È Ì ̤ÙÚÈ· Èı·ÓfiÙËÙ· Ë Û¯¤ÛË Ô˘ ÌÂÏÂÙ¿Ù·È Ó· Â›Ó·È ·ÈÙÈÔÏÔÁÈ΋, Ì ·ÔÙÂϤÛÌ·Ù· ¿ÌÂÛ· ÂÊ·ÚÌfiÛÈÌ· ÛÙÔÓ ÏËı˘ÛÌfi-ÛÙfi¯Ô Î·È ·Ú·Ï‹ÛÈ· ÌÂٷ͇ ÙˆÓ ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓØ ‹ Û˘ÁÎÂÓÙÚˆÙÈο ÛÙÔȯ›· ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜ ™∞ ÌÂÏÂÙÒÓ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ ‹ ‰È·¯ÚÔÓÈÎÒÓ ÌÂÏÂÙÒÓ ‹ ˘„ËÏ‹˜ ÔÈfiÙËÙ·˜ ÌÂÏÂÙÒÓ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ ‹ ‰È·¯ÚÔÓÈÎÒÓ ÌÂÏÂÙÒÓ Ì ÌÈÎÚfi ΛӉ˘ÓÔ ‡·Ú͢ Û˘Á¯˘ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, Ù˘¯·›Ô˘ ‹ ÛÊ¿ÏÌ·ÙÔ˜ Î·È Ì ÌÂÁ¿ÏË Èı·ÓfiÙËÙ· Ë Û¯¤ÛË Ô˘ ÌÂÏÂÙ¿Ù·È Ó· Â›Ó·È ·ÈÙÈÔÏÔÁÈ΋.

∞Ô‰ÂÎÙ¤˜ Û˘ÛÙ¿ÛÂȘ, ·ÛÊ·Ï›˜, ¯Ú‹ÛÈ̘ (¯Ú‹ÛË ÙˆÓ Ì¤¯ÚÈ ÙÒÚ· Û˘ÛÙ¿ÛˆÓ/Ô‰ËÁÈÒÓ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ٷ Ó¤· ‰Â‰Ô̤ӷ Ù˘ ¤Ú¢ӷ˜ ÎÚ›ÛË ÎÏÈÓÈÎÔ‡ È·ÙÚÔ‡).

D

ªË-·Ó·Ï˘ÙÈΤ˜ ÌÂϤÙ˜ .¯. ·ÚÔ˘ÛÈ¿ÛÂȘ ÂÚÈÛÙ·ÙÈÎÒÓ (case reports), ÛÂÈÚ¿ ÂÚÈÛÙ·ÙÈÎÒÓ (case series) ‹ ÁÓÒ̘ ÂȉÈÎÒÓ ‹ Û˘ÁÎÂÓÙÚˆÙÈο ÛÙÔȯ›· ηϿ ۯ‰ȷÛÌ¤ÓˆÓ ÌÂÏÂÙÒÓ ·ÛıÂÓÒÓ-Ì·ÚÙ‡ÚˆÓ ‹ ‰È·¯ÚÔÓÈÎÒÓ ÌÂÏÂÙÒÓ Ì ÌÈÎÚfi ΛӉ˘ÓÔ ‡·Ú͢ ·Ú·ÁfiÓÙˆÓ Û‡Á¯˘Û˘, Ù˘¯·›Ô˘ ‹ ÛÊ¿ÏÌ·ÙÔ˜ Î·È Ì ̤ÙÚÈ· Èı·ÓfiÙËÙ· Ë Û¯¤ÛË Ô˘ ÌÂÏÂÙ¿Ù·È Ó· Â›Ó·È ·ÈÙÈÔÏÔÁÈ΋.

ªË ·Ô‰ÂÎÙ¤˜ Û˘ÛÙ¿ÛÂȘ, ÌË ÙÂÎÌËÚȈ̤ÓÔ fiÊÂÏÔ˜, Èı·ÓfiÓ Î·È ‚Ï·‚ÂÚ¤˜ Û˘Ó¤ÂȘ.

i) ÙËÓ ÂÁ΢ÚfiÙËÙ· ÙÔ˘˜ (validity), ηٿ fiÛÔÓ ‰ËÏ·‰‹, Ù· ·Ó¢ÚÂı¤ÓÙ· ÛÙÔȯ›· Â›Ó·È ÎÔÓÙ¿ ÛÙËÓ ·Ï‹ıÂÈ· Î·È ÂÔ̤ӈ˜, ÌÔÚÔ‡Ó Ó· ÂÊ·ÚÌÔÛÙÔ‡Ó Ì ·ÍÈÔÈÛÙ›· ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË. Œ¯ÂÈ ÁÚ·ÊÙ› ÌÂÁ¿ÏÔ˜ ·ÚÈıÌfi˜ ÂÁ¯ÂÈÚȉ›ˆÓ fiÔ˘ ÂÚÈÁÚ¿ÊÔÓÙ·È ÂÚˆÙËÌ·ÙÔÏfiÁÈ· ·ÍÈÔÏfiÁËÛ˘ ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ÌÂıÔ‰ÔÏÔÁÈ΋˜ ÂÁ΢ÚfiÙËÙ·˜ ÌÈ·˜ ÎÏÈÓÈ΋˜ ÌÂϤÙ˘. ¶·Ú¿‰ÂÈÁÌ· ·ÍÈÔÏfiÁËÛ˘ ÂÓfi˜ ¿ÚıÚÔ˘/ÎÏÈÓÈ΋˜ ÌÂϤÙ˘ Ô˘ Ú·ÁÌ·Ù‡ÂÙ·È ÙË ıÂÚ·›· ÌÈ·˜ ÓfiÛÔ˘ ‰›‰ÂÙ·È ÛÙÔÓ ¶›Ó·Î· 6 (11). ii) ÙË ¯ÚËÛÈÌfiÙËÙ¿ ÙÔ˘˜ (usefulness), ηٿ fiÛÔÓ ‰ËÏ·‰‹, Ù· Â˘Ú‹Ì·Ù· Ù˘ ¤Ú¢ӷ˜ Â›Ó·È ÛËÌ·ÓÙÈο (important), ¯Ú‹ÛÈÌ· (useful), ¶·È‰È·ÙÚÈ΋ 2006;69:247-254

ÂÊ·ÚÌfiÛÈÌ· (applicable) ÛÙË ÎÏÈÓÈ΋ Ú¿ÍË Î·È Û¯ÂÙÈο (relevant) Ì ÙÔ ·Ú¯ÈÎfi ÎÏÈÓÈÎfi ÂÚÒÙËÌ· (‚Ϥ ¶›Ó·Î· 6).

∂Ê·ÚÌÔÁ‹ ÂӉ›ÍÂˆÓ ∏ ÂÊ·ÚÌÔÁ‹ ÙˆÓ ÂӉ›ÍˆÓ, Ô˘ ¤¯Ô˘ÌÂ Û˘ÏϤÍÂÈ ÌÂÙ¿ ·fi ÌÂıÔ‰È΋ ¤Ú¢ӷ Î·È ·ÓÙÈÎÂÈÌÂÓÈ΋ ·ÍÈÔÏfiÁËÛË, ·ÔÙÂÏ› ÙËÓ ÎÂÓÙÚÈ΋ ȉ¤· Ù˘ π·ÙÚÈ΋˜ µ·ÛÈ˙fiÌÂÓ˘ ÛÙȘ ∂Ӊ›ÍÂȘ (Evidence Based Medicine - apply conclusions), Î·È ÔÚ›˙ÂÙ·È Û˘ÓÔÙÈο ˆ˜ Ë Ï‹„Ë È·ÙÚÈÎÒÓ ·ÔÊ¿ÛÂˆÓ Î·È Ë ¿ÛÎËÛË È·ÙÚÈÎÒÓ ·ÚÂÌ‚¿ÛˆÓ

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π·ÙÚÈ΋ ‚·ÛÈṲ̂ÓË ÛÙȘ ÂӉ›ÍÂȘ

¶›Ó·Î·˜ 6. ∞ÍÈÔÏfiÁËÛË ¿ÚıÚÔ˘ Ô˘ Ú·ÁÌ·Ù‡ÂÙ·È ıÂÚ·›· ÓfiÛÔ˘ 1) ∂›Ó·È ¤Á΢ڷ Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘; ➤ •ÂΛÓËÛ·Ó ÔÈ ÔÌ¿‰Â˜ ÌÂϤÙ˘ Î·È Û‡ÁÎÚÈÛ˘ Ì ÙȘ ›‰È˜ Èı·ÓfiÙËÙ˜ ÚfiÁÓˆÛ˘; ñ ◊Ù·Ó ÔÈ ·ÛıÂÓ›˜ Ù˘¯·ÈÔÔÈË̤ÓÔÈ; ñ ◊Ù·Ó Ë Ù˘¯·ÈÔÔ›ËÛË Ù˘ÊÏ‹; ñ ªÂÏÂÙ‹ıËÎ·Ó ÔÈ ·ÛıÂÓ›˜ ÛÙȘ ·Ú¯ÈΤ˜ ÔÌ¿‰Â˜ (ÌÂϤÙ˘ ‹ Û‡ÁÎÚÈÛ˘) Ô˘ ›¯·Ó Ù˘¯·ÈÔÔÈËı›; (ÌÂÙ·‹‰ËÛË ·ÛıÂÓÒÓ) ñ ◊Ù·Ó Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·ÛıÂÓÒÓ ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜ ·ÚÂÌÊÂÚ‹ fiÛÔÓ ·ÊÔÚ¿ ÁÓˆÛÙÔ‡˜ ÚÔÁÓˆÛÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜; ➤ ¢È·Ù‹ÚËÛ·Ó ÔÈ ÔÌ¿‰Â˜ ÌÂϤÙ˘ Î·È ÂϤÁ¯Ô˘ ·ÚfiÌÔÈ· ÚfiÁÓˆÛË ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ÎÏÈÓÈ΋˜ ÌÂϤÙ˘; ñ °ÓÒÚÈ˙·Ó ÔÈ ·ÛıÂÓ›˜ Û ÔÈ· ÔÌ¿‰· ·Ó‹ÎÔ˘Ó; ñ °ÓÒÚÈ˙·Ó ÔÈ ÎÏÈÓÈÎÔ› ÂÚ¢ÓËÙ¤˜ ÙËÓ Î·Ù·ÓÔÌ‹ ÙˆÓ ·ÛıÂÓÒÓ; ñ °ÓÒÚÈ˙·Ó ÔÈ ÎÏÈÓÈÎÔ› ·ÔÙÈÌËÙ¤˜ ÙÔ˘ ·ÔÙÂϤÛÌ·ÙÔ˜ Ù˘ ¤Ú¢ӷ˜ ÙËÓ Î·Ù·ÓÔÌ‹ ÙˆÓ ·ÛıÂÓÒÓ; ñ √ÏÔÎÏËÚÒıËÎÂ Ë ·Ú·ÎÔÏÔ‡ıËÛË (follow-up) ÙˆÓ ·ÛıÂÓÒÓ; 2) ¶ÔÈ· ‹Ù·Ó Ù· ·ÔÙÂϤÛÌ·Ù·; ➤ ¶fiÛÔ ÌÂÁ¿ÏÔ ‹Ù·Ó ÙÔ ıÂÚ·¢ÙÈÎfi ·ÔÙ¤ÏÂÛÌ·; (treatment effect) ➤ ¶fiÛÔ ·ÎÚÈ‚‹˜ ‹Ù·Ó Ë ÂÎÙ›ÌËÛË ÙÔ˘ ıÂÚ·¢ÙÈÎÔ‡ ·ÔÙÂϤÛÌ·ÙÔ˜; (confidence intervals) 3) ¶Ò˜ ÌÔÚÒ Ó· ÂÊ·ÚÌfiÛˆ Ù· ·ÔÙÂϤÛÌ·Ù· ÛÙÔÓ ‰ÈÎfi ÌÔ˘ ·ÛıÂÓ‹; ➤ ◊Ù·Ó Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ÌÂϤÙ˘ ·ÚfiÌÔÈ· Ì ٷ ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ·ÛıÂÓÔ‡˜ ÌÔ˘; ➤ §‹ÊıËÎ·Ó ˘fi„Ë fiÏ· Ù· ÛËÌ·ÓÙÈο ÎÏÈÓÈο ·ÔÙÂϤÛÌ·Ù·; (ıÂÙÈο Î·È ·ÚÓËÙÈο) ➤ ∆· Èı·Ó¿ ÏÂÔÓÂÎÙ‹Ì·Ù· Ù˘ Û˘ÁÎÂÎÚÈ̤Ó˘ ıÂÚ·›·˜ ·ÓÙÈÛÙ·ıÌ›˙Ô˘Ó Û fiÊÂÏÔ˜ ÙȘ Èı·Ó¤˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Î·È ÙÔ ÎfiÛÙÔ˜;

Ô˘ ‚·Û›˙ÔÓÙ·È ÛÙ· Â˘Ú‹Ì·Ù· Ù˘ ÙÚ¤¯Ô˘Û·˜ ¤Ú¢ӷ˜. ∆· ÂÚˆÙ‹Ì·Ù· Ô˘ ·Ó·‰‡ÔÓÙ·È ÛÙÔ ÛËÌÂ›Ô ·˘Ùfi ÁÈ· ÙÔÓ ÎÏÈÓÈÎfi È·ÙÚfi Â›Ó·È ÔÏÏ¿: ∆È ·fi fiÏ· ·˘Ù¿ ÌÔÚ› Ó· ÂÊ·ÚÌÔÛÙ› ÛÙËÓ Ú¿ÍË; ¶fiÛÔ ·ÓÙÈÎÚÔ‡ÔÓÙ·È Ì ٷ fiÛ· ÁÓÒÚÈ˙Â Î·È ¯ÚËÛÈÌÔÔÈÔ‡Û ̤¯ÚÈ Û‹ÌÂÚ·; ∫·Ù¿ fiÛÔÓ Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÂÚ¢ÓÒÓ Ô˘ ·ÊÔÚÔ‡Ó ÙË Ì¤ÛË ¤Î‚·ÛË ÌÈ·˜ ÔÌ¿‰·˜ ·ÙfiÌˆÓ ÌÔÚÔ‡Ó Ó· ÂÓۈ̷وıÔ‡Ó ÛÙȘ ·Ó¿ÁΘ, ÛÙȘ ÚÔÛ‰Ô˘ Î·È ÛÙȘ ÚÔÙÈÌ‹ÛÂȘ ÂÓfi˜ ·ÛıÂÓÔ‡˜; ¢ÂÓ Â›Ó·È Û¿ÓÈÔ, ¤Ó·˜ ÎÏÈÓÈÎfi˜ È·ÙÚfi˜, ÌÂÙ¿ ·fi ÌÈ· ÂÍ·ÓÙÏËÙÈ΋ ¤Ú¢ӷ Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜, Ó· ηٷϋÍÂÈ ÛÂ Û˘ÌÂÚ¿ÛÌ·Ù· Î·È ·ÔÊ¿ÛÂȘ Ô˘, ‰˘ÓËÙÈο, ı· ÌÔÚÔ‡Û ӷ Ï¿‚ÂÈ Ì ÙȘ ¤ˆ˜ ÂΛÓË ÙË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ ÁÓÒÛÂȘ ÙÔ˘. ∏ Ú·ÎÙÈ΋ πµ∂ ÙÔ˘ ‰›ÓÂÈ ÙËÓ Â˘Î·ÈÚ›· Ó· ‰È·ÛÙ·˘ÚÒÛÂÈ ÙȘ ÁÓÒÛÂȘ, ÙȘ ÂÌÂÈڛ˜ -Î·È ÁÈ·Ù› fi¯È- ÙËÓ ÚˆÙ·Ú¯È΋ ‰È·›ÛıËÛ‹ ÙÔ˘ ÁÈ· ÙË Ï‹„Ë Ù˘ ÛˆÛÙfiÙÂÚ˘ ·fiÊ·Û˘. ∂ÈϤÔÓ, Ë ¯Ú‹ÛË Ù˘ πµ∂ ÛÙËÓ Î·ıË̤ڷ Ú¿ÍË Û˘Ì‚¿ÏÏÂÈ ÛÙÔ Ó· ·ÔʇÁÔÓÙ·È ÂÙÂÚÔ¯ÚÔÓÈṲ̂Ó˜ ‹ ·ÎfiÌ· Î·È ÂÚÈÙÙ¤˜ ·Ú·ÎÏÈÓÈΤ˜ ÂÍÂÙ¿ÛÂȘ Î·È ıÂÚ·›˜, Ô˘ ı· ÌÔÚÔ‡Û·Ó Ó· Ô‰ËÁ‹ÛÔ˘Ó Û ·ÌÊ›‚ÔÏÔ ÎÏÈÓÈÎfi ·ÔÙ¤ÏÂÛÌ· Î·È ¿ÛÎÔË Ù·Ï·ÈˆÚ›· ÙÔ˘ ·ÛıÂÓÔ‡˜. ŸÏ˜ ÔÈ ÎÏÈÓÈΤ˜ ÂӉ›ÍÂȘ, ÔÈ ÌÂϤÙ˜, ÔÈ ¤Ú¢Ó˜ ÌÔÚÔ‡Ó Ó· ÏËÚÔÊÔÚ‹ÛÔ˘Ó Î·È Ó· ÂÓËÌÂÚÒÛÔ˘Ó, ·ÏÏ¿ Û η̛· ÂÚ›ÙˆÛË ‰ÂÓ ÌÔÚÔ‡Ó Ó· ·ÓÙÈηٷÛÙ‹ÛÔ˘Ó ÙËÓ ÂÌÂÈÚ›· ηÈ

ÙȘ ÁÓÒÛÂȘ ÂÓfi˜ ÂȉÈÎÔ‡ ÎÏÈÓÈÎÔ‡ È·ÙÚÔ‡. √ ¤ÌÂÈÚÔ˜ ÎÏÈÓÈÎfi˜ Â›Ó·È ·˘Ùfi˜ Ô˘ ı· ·ÔÊ·Û›ÛÂÈ Ò˜ ı· ¯ÚËÛÈÌÔÔÈ‹ÛÂÈ ·˘Ù¤˜ ÙȘ Ӥ˜ ÁÓÒÛÂȘ Î·È Ò˜ ı· ÙȘ “·ÓÙÚ¤„ÂÈ” Ì ÙȘ ·Í›Â˜ Î·È È‰È·ÈÙÂÚfiÙËÙ˜ ÙÔ˘ οı ·ÛıÂÓÔ‡˜ Î·È ÛÂ Û˘ÓÂÚÁ·Û›· Ì·˙› ÙÔ˘ Ó· ÏËÊı› Ë Î·Ï‡ÙÂÚË ÎÏÈÓÈ΋ ·fiÊ·ÛË (2).

™˘ÌÂÚ¿ÛÌ·Ù· ∏ (¶·È‰)π·ÙÚÈ΋ µ·ÛÈṲ̂ÓË ÛÙȘ ∂Ӊ›ÍÂȘ (Evidence Based Medicine/ Evidence Based Pediatrics) ‰ÂÓ ‰È‰¿ÛÎÂÈ Î·ÓfiÓ˜ ‰Ú¿Û˘ Û οÔÈÔ ÎÏÈÓÈÎfi Úfi‚ÏËÌ·, ·ÏÏ¿ ·ÔÙÂÏ› ÂÚÁ·ÏÂ›Ô ÎÚÈÙÈ΋˜ Î·È ‰ÔÌË̤Ó˘ ÛΤ„˘, ·ÊÔ‡ Ë Û˘ÏÏÔÁ‹ ‰Â‰ÔÌ¤ÓˆÓ ·fi ÙËÓ ÙÚ¤¯Ô˘Û· ‚È‚ÏÈÔÁÚ·Ê›· ·ÔÙÂÏ› ¤Ó· ÌfiÓÔ Ì¤ÚÔ˜ Ù˘ ‰È·‰Èηۛ·˜ Ï‹„˘ ‰È·ÁÓˆÛÙÈÎÒÓ Î·È ıÂÚ·¢ÙÈÎÒÓ ·ÔÊ¿ÛˆÓ. ∂›Ó·È Ë Á¤Ê˘Ú· ÌÂٷ͇ È·ÙÚÈ΋˜ ¤Ú¢ӷ˜ Î·È ÎÏÈÓÈ΋˜ ‰Ú¿Û˘. √È ·Ú¯¤˜ Ô˘ ‰È¤Ô˘Ó ÙËÓ πµ∂ Â›Ó·È Ë ÌÂÙ·ÙÚÔ‹ ÂÓfi˜ ÎÏÈÓÈÎÔ‡ ÚÔ‚Ï‹Ì·ÙÔ˜ Û ۈÛÙ¿ ‰ÔÌË̤ÓË ÂÚÒÙËÛË Ô˘ ÌÔÚ› Ó· ··ÓÙËı› (ÏËı˘ÛÌfi˜ - ·Ú¤Ì‚·ÛË - ·ÔÙ¤ÏÂÛÌ·), ÂÓÒ ·ÎÔÏÔ˘ı› Ë ·Ó·˙‹ÙËÛË Î·È Ë ·ÍÈÔÏfiÁËÛË ÙˆÓ ÈÔ ¤ÁÎ˘ÚˆÓ Î·È ÈÔ ·ÍÈfiÈÛÙˆÓ Ì¤¯ÚÈ Û‹ÌÂÚ· ÂӉ›ÍˆÓ. ™Ùfi¯Ô˜, ÏÔÈfiÓ, ÙÔ˘ ÎÏÈÓÈÎÔ‡ È·ÙÚÔ‡ Ô˘ ¯ÚËÛÈÌÔÔÈ› πµ∂ ‰ÂÓ Â›Ó·È Ë ·¤Ó·Ë ÚÔÛ¿ıÂÈ· ·fiÎÙËÛ˘ ¶·È‰È·ÙÚÈ΋ 2006;69:247-254

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Ó¤ˆÓ Î·È ÂÎÛ˘Á¯ÚÔÓÈÛÌ¤ÓˆÓ ÁÓÒÛˆÓ, ·ÏÏ¿ Ë ÔÚıÔÏÔÁÈ΋ ¯ÚËÛÈÌÔÔ›ËÛ‹ ÙÔ˘˜ ÒÛÙ ӷ ÚÔÛʤÚÂÈ Â˘ÓÔïÎfiÙÂÚ˜ ÚÔ¸Ôı¤ÛÂȘ ÁÈ· ÙËÓ Î·Ï‡ÙÂÚË ÔÚ›· ÙˆÓ ·ÛıÂÓÒÓ ÙÔ˘ (12).

µÈ‚ÏÈÔÁÚ·Ê›· 1. ªÔ˘ÓÙÔηϿ΢ £.¢. π·ÙÚÈ΋ ‚·ÛÈ˙fiÌÂÓË Û ÂӉ›ÍÂȘ ÌÈ· ÚÒÙË Ì·ÙÈ¿. Evidence Based Medicine. π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘- °·ÛÙÚÂÓÙÂÚÔÏÔÁÈ΋ ∫ÏÈÓÈ΋. 2001.

2. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence Based Medicine: what it is and what it isn’t. BMJ 1996;312:71-72.

3. Elphick HE, Smyth RL. Research: the principles of evidence-based medicine. Current Paediatrics 2004; 14:525-531.

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¶·È‰È·ÙÚÈ΋ 2006;69:247-254

http://cebm.jr2.ox.ac.uk/docs/focusquest.html 6. Glasziou PP, Del Mar CB, Sanders SL, Hayem M. Antibiotics for acute otitis media in children [Cochrane Review]. The Cochrane Library, Issue 4.

Oxford: Update software, 2001.

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10. Baumer JH. Comparison of two otitis media guidelines. Archives of Disease in Childhood Education and Practice Edition 2004;89:76-78.

11. Guyatt G, Cook D, Devereaux PJ, Meade M, Straus S. Therapy. In: Guyatt G, Rennie D. Users’ Guides to the medical literature.1st ed. USA: American Medical Association; 2002.

12. Bauchner H. Evidence-based Medicine: A new science or an epidemiologic fad? Pediatrics 1999; 103:1029-1031.

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°ÔÓ›‰È· Î·È Ì˯·ÓÈÛÌÔ› ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ ¶.¶. ¶¤ÙÚÔ˘

¶·ÓÂÈÛÙ‹ÌÈÔ ∫Ú‹Ù˘, ∆Ì‹Ì· µÈÔÏÔÁ›·˜

¶ÂÚ›ÏË„Ë: √ ·Ó·Ù˘ÛÛfiÌÂÓÔ˜ ÓÂÊÚfi˜ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Â˘Ú¤ˆ˜ ˆ˜ ÂÈÚ·Ì·ÙÈÎfi Û‡ÛÙËÌ· ÁÈ· ÙË ‰ÈÂÚ‡ÓËÛË ‚·ÛÈÎÒÓ Ì˯·ÓÈÛÌÒÓ ÔÚÁ·ÓÔÁ¤ÓÂÛ˘. ∏ ÌÔÚÊÔÁ¤ÓÂÛË ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘, ÙÔ˘ ÌfiÓÈÌÔ˘ ÓÂÊÚÔ‡ ÛÙÔÓ ÂÓ‹ÏÈη, ÂÚÈÏ·Ì‚¿ÓÂÈ ‰È·‰Èηۛ˜ fiˆ˜ ÂÈıËÏȷΤ˜-ÌÂÛÂÁ¯˘Ì·ÙÈΤ˜ ·ÏÏËÏÂȉڿÛÂȘ, ‰È·ÎÏ¿‰ˆÛË ÂÈıËÏ›ˆÓ, ÂÈıËÏÈÔÔ›ËÛË ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È Î˘ÙÙ·ÚÈ΋ ‰È·ÊÔÚÔÔ›ËÛË. √È ·Ú·¿Óˆ ‰ÈÂÚÁ·Û›Â˜ Û˘ÓÙÔÓ›˙ÔÓÙ·È ·fi ÌÈ· ÛÂÈÚ¿ ·ÌÊ›‰ÚÔÌˆÓ ÛËÌ·ÙÔ‰ÔÙ‹ÛÂˆÓ ÌÂٷ͇ ‰‡Ô ÂÌ‚Ú˘˚ÎÒÓ ÈÛÙÒÓ Ô˘ ÚÔ·ÙÔ˘Ó ·fi ÙÔ ‰È¿ÌÂÛÔ ÌÂÛfi‰ÂÚÌ·, Ù˘ Ô˘ÚËÙËÚÈ΋˜ ηٷ‚ÔÏ‹˜ Î·È ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ηıÒ˜ Â›Û˘ Î·È ÙˆÓ ·Ú·ÁÒÁˆÓ ÙÔ˘˜. ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Ë ·ÍÈÔÔ›ËÛË ÙÔ˘ ÔÓÙÈÎÔ‡ ˆ˜ ÂÈÚ·Ì·ÙÈÎfi ÌÔÓÙ¤ÏÔ Â›Ù ÁÈ· ÙËÓ ·ÂÓÂÚÁÔÔ›ËÛË ÁÔÓȉ›ˆÓ, ›Ù ÁÈ· ÙË ‰ËÌÈÔ˘ÚÁ›· ‰È·ÁÔÓȉȷÎÒÓ ˙ÒˆÓ, ¤¯ÂÈ Û˘Ì‚¿ÏÂÈ ÛËÌ·ÓÙÈο ÛÙÔÓ ¯·Ú·ÎÙËÚÈÛÌfi ÌÔÚÈ·ÎÒÓ Ì˯·ÓÈÛÌÒÓ Î·È ÛÙËÓ Ù·˘ÙÔÔ›ËÛË ÁÔÓȉȷÎÒÓ ÚÔ˚fiÓÙˆÓ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ. ¶·ÚfiÏË ÙËÓ ¤ÓÙÔÓË ÂÚ¢ÓËÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ· ÛÙÔ ‰›Ô Ù˘ ÌÔÚÊÔÁ¤ÓÂÛ˘ ÙˆÓ ÓÂÊÚÒÓ, ÔÏÏ¿ ÂÚˆÙ‹Ì·Ù· ·Ú·Ì¤ÓÔ˘Ó ·ÎfiÌË ·Ó·¿ÓÙËÙ·. ∏ ÂÊ·ÚÌÔÁ‹ Û‡Á¯ÚÔÓˆÓ, ÂÍÂÏÈÁÌ¤ÓˆÓ Ù¯ÓÈÎÒÓ ÁÂÓÂÙÈ΋˜ ÙÚÔÔÔ›ËÛ˘ ÛÙÔÓ ÔÓÙÈÎfi ·Ó·Ì¤ÓÂÙ·È Ó· ‰ÒÛÂÈ ··ÓÙ‹ÛÂȘ Û οÔÈ· ·fi ·˘Ù¿. ∏ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË ·Ó·Ê¤ÚÂÙ·È ÛÙ· ΢ÚÈfiÙÂÚ· ÛÙ¿‰È· Ù˘ ·Ó¿Ù˘Í˘ ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘, ηıÒ˜ Î·È ÛÙ· ÁÔÓ›‰È· Ô˘ ÂÌϤÎÔÓÙ·È ÛÙÔ Î·ı¤Ó· ·fi ·˘Ù¿. §fiÁˆ ÙˆÓ ÂÚÈÔÚÈÛÌÒÓ ÛÙËÓ ¤ÎÙ·ÛË ÙÔ˘ ÎÂÈ̤ÓÔ˘, ·Ó·Ê¤ÚÔÓÙ·È ÌfiÓÔ ÔÈ Î˘ÚÈfiÙÂÚÔÈ ·Ú¿ÁÔÓÙ˜ ÁÈ· ÙÔ Î¿ı ÛÙ¿‰ÈÔ, ÂÓÒ ·Ú¿ÏÏËÏ· ·Ú·Ù›ıÂÙ·È Î·È Ë ÚfiÛÊ·ÙË ‚È‚ÏÈÔÁÚ·Ê›·.

AÏÏËÏÔÁÚ·Ê›·: ¶.¶. ¶¤ÙÚÔ˘ ¶·ÓÂÈÛÙ‹ÌÈÔ ∫Ú‹Ù˘, ∆Ì‹Ì· µÈÔÏÔÁ›·˜ 71 409 ∏Ú¿ÎÏÂÈÔ, ∫Ú‹ÙË E-mail: petrou@imbb.forth.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 20-09-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 02-12-2005

§¤ÍÂȘ ÎÏÂȉȿ: NÂÊÚfi˜, ÁÔÓ›‰È·, ÔÓÙÈÎfi˜, Ô˘ÚËÙËÚÈ΋ ηٷ‚ÔÏ‹, ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì·.

Genes and mechanisms in kidney development P.P. Petrou

University of Crete, Department of Biology

Abstract: The developing kidney is widely used as an experimental system for the study of fundamental mechanisms of organogenesis. Morphogenesis of the metanephros, the permanent kidney in the adult, includes processes such as epithelial-mesenchymal interactions, epithelial branching, mesenchymal-to-epithelial transition and cell differentiation. These processes are coordinated by a series of reciprocal signaling events between two embryonic tissues derived from the intermediate mesoderm, the ureteric bud and the metanephric mesenchyme, and their descendants.

The use of the mouse as an experimental model, either for the inactivation of genes or for the generation of transgenic animals, has greatly contributed in the characterization of molecular mechanisms and the identification of gene products involved in kidney development. However, despite the intensive experimental activity in the field of kidney morphogenesis many questions remain to be answered. Recently developed powerful techniques of genetic manipulation in the mouse are expected to provide insight into some of the so far unknown aspects of kidney development. This review reports on the main stages of kidney development and the most important genes involved in each stage.

Correspondence: P.P. Petrou University of Crete, Department of Biology 71 409, Herakleion, Crete E-mail: petrou@imbb.forth.gr Date of submission: 20-09-2005 Date of approval: 02-12-2005

Key words: Kidney, genes, mouse, ureteric bud, metanehric mesenchyme.

EÈÛ·ÁˆÁ‹ ∏ ‰È·‰Èηۛ· Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ ÓÂÊÚÒÓ ÛÙÔÓ ¿ÓıÚˆÔ ÌÔÚ› Ó· ıˆÚËı› ˆ˜ ÌÈ· Û‡-

ÓÙÔÌË ·Ó·‰ÚÔÌ‹ ÛÙËÓ ÈÛÙÔÚ›· Ù˘ ÂͤÏÈ͢ ÙÔ˘ ÂÎÎÚÈÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÙˆÓ ¯ÂÚÛ·›ˆÓ ÛÔÓ‰˘ÏˆÙÒÓ. ∫·Ù¿ ÙË ÓÂÊÚÔÁ¤ÓÂÛË ÂÌÊ·Ó›˙ÔÓÙ·È ÙÚ›· Û˘ÛÙ‹Ì·Ù· ÓÂÊÚÒÓ, Ù· ÔÔ›· Â›Ó·È ¶·È‰È·ÙÚÈ΋ 2006;69:255-267

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·Ú¿ÁˆÁ· ÙÔ˘ ‰È¿ÌÂÛÔ˘ ÌÂÛÔ‰¤ÚÌ·ÙÔ˜ Î·È ‰È·‰¤¯ÔÓÙ·È ÙÔ ¤Ó· ÙÔ ¿ÏÏÔ. ∫ÂÊ·ÏÈÎfiÙÂÚ· Û¯ËÌ·Ù›˙ÔÓÙ·È ÔÈ ÚfiÓÂÊÚÔÈ, ÔÈ ÔÔ›ÔÈ Â›Ó·È ÌË ÏÂÈÙÔ˘ÚÁÈÎÔ› Î·È ·ÔÙÂÏÔ‡Ó ÙÔÓ ÈÔ ÚˆÙfiÁÔÓÔ Ù‡Ô ÓÂÊÚÒÓ ÙˆÓ ÛÔÓ‰˘ÏˆÙÒÓ (∂ÈÎfiÓ· 1∞). ∞˘ÙÔ› ÂÌÊ·Ó›˙ÔÓÙ·È Î·Ù¿ ÙËÓ 3Ë Â‚‰ÔÌ¿‰· Ù˘ ·ËÛ˘ Î·È ÂÎÊ˘Ï›˙ÔÓÙ·È Û‡ÓÙÔÌ· ÁÈ· Ó· ÙÔ˘˜ ‰È·‰Â¯ıÔ‡Ó ÔÈ ÌÂÛfiÓÂÊÚÔÈ, ÔÈ ÔÔ›ÔÈ ·Ó·Ù‡ÛÛÔÓÙ·È Ô˘Ú·ÈfiÙÂÚ· ÛÙÔ Â›Â‰Ô ÙÔ˘ 3Ô˘ ÔÛÊ˘˚ÎÔ‡ ÛÔÓ‰‡ÏÔ˘ Î·È Ë ·Ó¿Ù˘ÍË ÙÔ˘˜ ÔÏÔÎÏËÚÒÓÂÙ·È Î·Ù¿ ÙËÓ 8Ë Â‚‰ÔÌ¿‰· Ù˘ ·ËÛ˘ (∂ÈÎfiÓ· 1µ). √È ÌÂÛfiÓÂÊÚÔÈ ·ÔÙÂÏÔ‡Ó Ù· ·ÚÈ· ·ÂÎÎÚÈÙÈο fiÚÁ·Ó· ηٿ ÙËÓ ÂÌ‚Ú˘˚΋ ·Ó¿Ù˘ÍË. Ÿˆ˜ Î·È ÔÈ ÚfiÓÂÊÚÔÈ, ÔÈ ÌÂÛfiÓÂÊÚÔÈ ÂÍ·Ê·Ó›˙ÔÓÙ·È ÛÙ·‰È·Î¿ Î·È ‰ÂÓ ˘¿Ú¯Ô˘Ó ÛÙÔÓ ÂÓ‹ÏÈη, Ì ÂÍ·›ÚÂÛË Û˘ÁÎÂÎÚÈ̤ӷ ÌfiÓÔ ÙÌ‹Ì·Ù· ÙˆÓ ÌÂÛÔÓÂÊÚÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ, Ù· ÔÔ›· ÂÓۈ̷ÙÒÓÔÓÙ·È ÛÙÔ ·Ó··Ú·ÁˆÁÈÎfi Û‡ÛÙËÌ· ÛÙÔ ¿ÚÚÂÓ. ∆¤ÏÔ˜, ÔÈ ÌÂÙ¿ÓÂÊÚÔÈ ·Ú¯›˙Ô˘Ó Ó· ·Ó·Ù‡ÛÛÔÓÙ·È Î·Ù¿ ÙËÓ 5Ë Â‚‰ÔÌ¿‰·, Ô˘Ú·ÈfiÙÂÚ· ·fi Ù· ¿ÏÏ· ‰‡Ô ÚÔ·Ó·ÊÂÚı¤ÓÙ· ›‰Ë ÓÂÊÚÒÓ Î·È ˆÚÈÌ¿˙Ô˘Ó ÏÂÈÙÔ˘ÚÁÈο ÚÔ˜ ÙÔ Ù¤ÏÔ˜ Ù˘ ÂÌ‚Ú˘˚΋˜ ·Ó¿Ù˘Í˘, ηıÒ˜ ÔÈ ÌÂÛfiÓÂÊÚÔÈ ÂÎÊ˘Ï›˙ÔÓÙ·È. √È ÌÂÙ¿ÓÂÊÚÔÈ, ÛÙÔ˘˜ ÔÔ›Ô˘˜ ı· ·Ó·ÊÂÚıԇ̠ÂÎÙÂÓ¤ÛÙÂÚ· ·Ú·Î¿Ùˆ, Â›Ó·È ÔÈ ÌfiÓÈÌÔÈ ÏÂÈÙÔ˘ÚÁÈÎÔ› ÓÂÊÚÔ› ÛÙÔÓ ÂÓ‹ÏÈη.

ªÔÚÊÔÁ¤ÓÂÛË ÙˆÓ ÌÂÙ¿ÓÂÊÚˆÓ ∏ ·Ó¿Ù˘ÍË ÙˆÓ ÌÂÙ¿ÓÂÊÚˆÓ ·Ú¯›˙ÂÈ Ì ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ Ô˘ÚËÙËÚÈ΋˜ ηٷ‚ÔÏ‹˜ (O∫), ÂÓfi˜ ÂÎÎÔÏÒÌ·ÙÔ˜ ÛÙÔ ÂÈı‹ÏÈÔ ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘ (1). ∞˘Ùfi ÂÈÛ‚¿ÏÏÂÈ Û ÌÈ· ÂÍÂȉÈÎÂ˘Ì¤ÓË ÂÚÈÔ¯‹ ÙÔ˘ ‰È¿ÌÂÛÔ˘ ÌÂÛÔ‰¤ÚÌ·ÙÔ˜, ÙÔ ÔÔ›Ô ÔÓÔÌ¿˙ÂÙ·È ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì· (∂ÈÎfiÓ˜ 1°, 2∞). ™˘ÓÂÒ˜, Ë ·Ó¿Ù˘ÍË ÙˆÓ ÌÂÙ¿ÓÂÊÚˆÓ ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ·ÏÏËÏÂ›‰Ú·ÛË Î·È ÙË Û˘Ì‚ÔÏ‹ ‰‡Ô ÂÌ‚Ú˘˚ÎÒÓ ÈÛÙÒÓ, Ù˘ √∫ ·fi ÙËÓ ÔÔ›· ÚÔ·ÙÂÈ Ô Ô˘ÚËÙ‹Ú·˜, Ë ÓÂÊÚÈ΋ ‡ÂÏÔ˜ Î·È Ù· ·ıÚÔÈÛÙÈο ÛˆÏËÓ¿ÚÈ· Î·È ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ÙÔ ÔÔ›Ô ·Ú¿ÁÂÈ ÙÔ˘˜ ÓÂÊÚÒÓ˜ (2-5). ø˜ Û˘Ó¤ÂÈ· Ù˘ ·ÏÏËÏÂ›‰Ú·Û˘ ÌÂٷ͇ ÙÔ˘ ÂÈıËÏ›Ô˘ Ù˘ √∫ Î·È ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ Â¿ÁÔÓÙ·È ÌÔÚÊÔÏÔÁÈΤ˜ ·ÏÏ·Á¤˜ Î·È ÛÙÔ˘˜ ‰‡Ô ·˘ÙÔ‡˜ ÂÌ‚Ú˘˚ÎÔ‡˜ ÈÛÙÔ‡˜, ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ÚÔ·ÙÂÈ Ô ÌÂÙ¿ÓÂÊÚÔ˜. ∆Ô ÂÈı‹ÏÈÔ Ù˘ √∫ ˘Ê›ÛÙ·Ù·È ÌÈ· ÛÂÈÚ¿ ‰È·‰Ô¯ÈÎÒÓ ÂÈÌË·ÓÛÂˆÓ Î·È ‰È·ÎÏ·‰ÒÛÂˆÓ (14-15 ÊÔÚ¤˜ ÛÙÔÓ ¿ÓıÚˆÔ) Ô˘ Ô‰ËÁÔ‡Ó ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÂÓfi˜ ‰ÈÎÙ‡Ô˘ ÛˆÏËÓ·Ú›ˆÓ, Ù· ÔÔ›· ·Ú¶·È‰È·ÙÚÈ΋ 2006;69:255-267

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∂ÈÎfiÓ· 1. ™¯ËÌ·ÙÈ΋ ·Ó··Ú¿ÛÙ·ÛË ÙˆÓ ÙÚÈÒÓ Û˘ÛÙËÌ¿ÙˆÓ ÓÂÊÚÒÓ Û ‰È·ÊÔÚÂÙÈο ÛÙ¿‰È· Ù˘ ÂÌ‚Ú˘ÔÁ¤ÓÂÛ˘. ∞) ™¯ËÌ·ÙÈÛÌfi˜ ÙˆÓ ÚÔÓÂÊÚÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ ηıÒ˜ Ô ÚÒÈÌÔ˜ ÓÂÊÚÈÎfi˜ fiÚÔ˜ ÂÂÎÙ›ÓÂÙ·È ÚÔ˜ ÙËÓ ·Ì¿Ú·. µ) √ ÌÂÛfiÓÂÊÚÔ˜ ‰ËÌÈÔ˘ÚÁÂ›Ù·È Î·ıÒ˜ Ô ÚfiÓÂÊÚÔ˜ ÂÎÊ˘Ï›˙ÂÙ·È. °) ∏ ·Ó¿Ù˘ÍË ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘ Û˘ÓÙÔÓ›˙ÂÙ·È ·fi ÙËÓ ·ÏÏËÏÂ›‰Ú·ÛË ‰‡Ô ÂÌ‚Ú˘˚ÎÒÓ ÈÛÙÒÓ, Ù˘ Ô˘ÚËÙËÚÈ΋˜ ηٷ‚ÔÏ‹˜, Ë ÔÔ›· ÂÎʇÂÙ·È ·fi ÙÔ ÂÈı‹ÏÈÔ ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘ Î·È ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜. √ ÌÂÛfiÓÂÊÚÔ˜ ÛÙ·‰È·Î¿ ÂÍ·Ê·Ó›˙ÂÙ·È.

ÁfiÙÂÚ· ı· ‰È·ÊÔÚÔÔÈËıÔ‡Ó ÛÙ· ÒÚÈÌ· ·ıÚÔÈÛÙÈο ÛˆÏËÓ¿ÚÈ· ÙÔ˘ ÓÂÊÚÔ‡. ∞fi ÙËÓ ¿ÏÏË, Ù· ·ÙÙ·Ú· ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ·Ú¯›˙Ô˘Ó Ó· ˘ÎÓÒÓÔ˘Ó ÛÙȘ ÎÔÚ˘Ê¤˜ ÙÔ˘ ‰È·ÎÏ·‰È˙fiÌÂÓÔ˘ ÂÈıËÏ›Ô˘ (∂ÈÎfiÓ· 2µ). ™˘Ì·Á›˜ ÔÌ¿‰Â˜ Ù¤ÙÔÈˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÌÂÙ·ÙÚ¤ÔÓÙ·È ·ÎÔÏÔ‡ıˆ˜ Û ÂÈıËÏȷο, Ù· ÔÔ›· Û¯ËÌ·Ù›˙Ô˘Ó ÌÈÎÚ¿ ΢ÛÙ›‰È· (∂ÈÎfiÓ· 2°). ∞˘Ù¿, ·ÎÔÏÔ˘ıÔ‡Ó ÌÈ· ÛÙÂÚÂfiÙ˘Ë ÛÂÈÚ¿ ÌÔÚÊÔÁÂÓÂÙÈÎÒÓ ·ÏÏ·ÁÒÓ Î·È ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ÛÈÁÌÔÂȉ‹ ÛˆÏËÓ¿ÚÈ·, ÙˆÓ ÔÔ›ˆÓ ÙÔ ¤Ó· ¿ÎÚÔ Û˘Ó‰¤ÂÙ·È Ì ÙÔ ·Ú·Î›ÌÂÓÔ ·ıÚÔÈÛÙÈÎfi ÛˆÏËÓ¿ÚÈÔ, ÂÓÒ ÛÙÔ ¿ÏÏÔ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È Ù· ÓÂÊÚÈο ÛÂÈÚ¿Ì·Ù· Ì ÙËÓ ÂÈÛ¯ÒÚËÛË ÙÚȯÔÂȉÒÓ ·ÈÌÔÊfiÚˆÓ ·ÁÁ›ˆÓ (∂ÈÎfiÓ˜ 2¢-∂). √È ÚÒÈ̘ ·˘Ù¤˜ ‰Ô̤˜ ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘ ˘Ô‚¿ÏÏÔÓÙ·È ÛÙË Û˘Ó¤¯ÂÈ· ÛÙË ‰È·‰Èηۛ· Ù˘ ˆÚ›Ì·ÓÛ˘, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰ËÌÈÔ˘ÚÁ›· ·Ó·ÙÔÌÈο Î·È Ê˘ÛÈÔÏÔÁÈο ͯˆÚÈÛÙÒÓ ‰ÔÌÒÓ, fiˆ˜ ÙÔ ÂÁÁ‡˜ ÂÛÂÈڷ̤ÓÔ ÛˆÏËÓ¿ÚÈÔ, Ë ·Á·ÏË ÙÔ˘ Henle Î·È ÙÔ ¿ˆ ÂÛÂÈڷ̤ÓÔ ÛˆÏËÓ¿ÚÈÔ (∂ÈÎfiÓ· 2∂). ∏ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ ÂÚÈÏ·Ì‚¿ÓÂÈ ‰È·‰Èηۛ˜ fiˆ˜ ÂÈıËÏȷΤ˜-ÌÂÛÂÁ¯˘Ì·ÙÈΤ˜

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∂ÈÎfiÓ· 2. ¢ËÌÈÔ˘ÚÁ›· ÙˆÓ ÓÂÊÚÒÓˆÓ. ∞) Ë Ô˘ÚËÙËÚÈ΋ ηٷ‚ÔÏ‹ (√∫) ÌÂÙ¿ ÙËÓ Â·ÁˆÁ‹ Ù˘ ÂÈÛ‚¿ÏÏÂÈ ÛÙÔ Î·ıÔÚÈṲ̂ÓÔ ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì· (ªª). µ) ™ËÌ·ÙÔ‰ÔÙÈο ÌfiÚÈ· ·fi ÙÔ ªª ÚÔηÏÔ‡Ó ÙË Û˘Ì‡ÎÓˆÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÛÙȘ ÎÔÚ˘Ê¤˜ Ù˘ √∫. °) ∆· Û˘Ì˘Îӈ̤ӷ ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· (™ª) ÂÈıËÏÈÔÔÈÔ‡ÓÙ·È Î·È Û¯ËÌ·Ù›˙Ô˘Ó Î˘ÛÙ›‰È· (¡∫) Ù· ÔÔ›· ·ÎÔÏÔ‡ıˆ˜ ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È (¢) Û ÛÈÁÌÔÂȉ‹ ÛˆÏËÓ¿ÚÈ· (S). ∂) ∫·Ù¿ ÙË ‰È·‰Èηۛ· Ù˘ ˆÚ›Ì·ÓÛ˘ ÙÔ ¤Ó· ¿ÎÚÔ ÙˆÓ ÓÂÊÚÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ Û˘Ó‰¤ÂÙ·È Ì ÙÔ ·ıÚÔÈÛÙÈÎfi ÛˆÏËÓ¿ÚÈÔ (∞ı™), ÂÓÒ ÛÙÔ ¿ÏÏÔ ‰ËÌÈÔ˘ÚÁÂ›Ù·È ÙÔ ÓÂÊÚÈÎfi Û›ڷ̷ (¡™) Ì ÙËÓ ÂÈÛ¯ÒÚËÛË ÙÚȯÔÂȉÒÓ ·ÈÌÔÊfiÚˆÓ ·ÁÁ›ˆÓ. ∆Ì‹Ì·Ù· ÙˆÓ ÓÂÊÚÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û ·Ó·ÙÔÌÈο Î·È ÏÂÈÙÔ˘ÚÁÈο ͯˆÚÈÛÙ¤˜ ‰Ô̤˜, fiˆ˜ ÙÔ ÂÁÁ‡˜ (∂™) Î·È ¿ˆ (∞™) ÛˆÏËÓ¿ÚÈÔ Î·È Ë ·Á·ÏË ÙÔ˘ Henle (H). B: ο„· ÙÔ˘ Bowman.

·ÏÏËÏÂȉڿÛÂȘ, ‰È·ÎÏ¿‰ˆÛË ÂÈıËÏ›ˆÓ, ΢ÙÙ·ÚÈ΋ ‰È·ÊÔÚÔÔ›ËÛË, ÌÂÙ·Û¯ËÌ·ÙÈÛÌfi ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Û ÂÈıËÏȷο Î·È ÌÔÚÊÔÁ¤ÓÂÛË, ÔÈ Ôԛ˜ ÌÔÚÔ‡Ó Ó· ÌÂÏÂÙËıÔ‡Ó ÛÂ Û˘ÛÙ‹Ì·Ù· in vitro ÈÛÙÔηÏÏȤÚÁÂÈ·˜. °È· ÙÔ˘˜ ·Ú·¿Óˆ ÏfiÁÔ˘˜, Ë ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ ·ÔÙÂÏ› Â‰Ò Î·È ¿Óˆ ·fi 40 ¯ÚfiÓÈ· ¤Ó· ȉ·ÓÈÎfi Û‡ÛÙËÌ· ÁÈ· ÙË ÌÂϤÙË ‚·ÛÈÎÒÓ ·Ú¯ÒÓ Ù˘ ·Ó·Ù˘Íȷ΋˜ ‚ÈÔÏÔÁ›·˜ Î·È ÔÚÁ·ÓÔÁ¤ÓÂÛ˘. ™ÙËÓ Ù·˘ÙÔÔ›ËÛË ÙÔ˘ ÚfiÏÔ˘ ÂÓfi˜ ÌÂÁ¿ÏÔ˘ ·ÚÈıÌÔ‡ ÁÔÓȉȷÎÒÓ ÚÔ˚fiÓÙˆÓ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ ¤¯ÂÈ Û˘Ì‚¿ÏÂÈ ÛËÌ·ÓÙÈο Ë ¯Ú‹ÛË ˙ˆÈÎÒÓ ÌÔÓ٤ψÓ, ÌÂٷ͇ ·˘ÙÒÓ Î·È ÙÔ˘ ÔÓÙÈÎÔ‡ (‚Ï. ¶›Ó·Î· 1). ¶·Ú·Î¿Ùˆ ·Ó·Ê¤ÚÔÓÙ·È Ù· ΢ÚÈfiÙÂÚ· ÛÙ¿‰È· Ù˘ ÓÂÊÚÈ΋˜ ·Ó¿Ù˘Í˘ Î·È ÔÈ ÛËÌ·ÓÙÈÎfiÙÂÚÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙÔ Î·ı¤Ó·.

∫·ıÔÚÈÛÌfi˜ (specification) ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ∞·Ú·›ÙËÙË ÚÔ¸fiıÂÛË ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÌÂÙ¿ÓÂÊÚˆÓ Â›Ó·È Ô Î·ıÔÚÈÛÌfi˜ ÙÔ˘ Ô˘Ú·›Ô˘ ¿ÎÚÔ˘ ÙÔ˘ ‰È¿ÌÂÛÔ˘ ÌÂÛÔ‰¤ÚÌ·ÙÔ˜ Î·È Ë ‰È·ÊÔÚÔÔ›ËÛ‹ ÙÔ˘ ÛÙÔ ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì·. √È ÌÔÚÈ·ÎÔ› Ì˯·ÓÈÛÌÔ› Ô˘ Ô‰ËÁÔ‡Ó ÛÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ·Ú·Ì¤ÓÔ˘Ó ·ÎfiÌ· ¿ÁÓˆÛÙÔÈ. øÛÙfiÛÔ, Ì ÂÈÚ¿Ì·Ù· ÛÙÔ¯Â˘Ì¤Ó˘ ·ÂÓÂÚÁÔÔ›ËÛ˘ ÁÔÓȉ›ˆÓ ÛÙÔÓ ÔÓÙÈÎfi

Ù·˘ÙÔÔÈ‹ıËÎ·Ó ÔÚÈṲ̂Ó˜ ÚˆÙ½Ó˜ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·Ú·¿Óˆ ‰È·‰Èηۛ·, ÔÈ Ôԛ˜ Â›Ó·È Î˘Ú›ˆ˜ ÌÂÙ·ÁÚ·ÊÈÎÔ› ·Ú¿ÁÔÓÙ˜. ∏ ÚˆÙ½ÓË Eya1*, ÔÌfiÏÔÁË ÙÔ˘ ÌÂÙ·ÁÚ·ÊÈÎÔ‡ ·Ú¿ÁÔÓÙ· eyes absent Ù˘ ‰ÚÔÛfiÊÈÏ·˜, Ê·›ÓÂÙ·È Ó· Â›Ó·È Ô ÚÒÙÔ˜ ·Ú¿ÁÔÓÙ·˜ Ô˘ ··ÈÙÂ›Ù·È ÁÈ· ÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜. ø˜ Û˘Ó¤ÂÈ· Ù˘ ·ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ ÁÔÓȉ›Ô˘ Eya1* ·Ú·ÙËÚÂ›Ù·È ·Ô˘Û›· ÙˆÓ ÌÂÙ¿ÓÂÊÚˆÓ, ÂÓÒ ÔÈ ÌÂÛfiÓÂÊÚÔÈ ·Ó·Ù‡ÛÛÔÓÙ·È Î·ÓÔÓÈο (6). ™Â ÔÓÙ›ÎÈ· ÌÂÙ·ÏÏ·Á̤ӷ ÁÈ· ÙÔ ÌÂÙ·ÁÚ·ÊÈÎfi ·Ú¿ÁÔÓÙ· Lim1, Ô ÔÔ›Ô˜ ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ homeodomain ÚˆÙÂ˚ÓÒÓ Î·È ÂÎÊÚ¿˙ÂÙ·È Î·Ù¿ Ì‹ÎÔ˜ ÙÔ˘ ‰È¿ÌÂÛÔ˘ ÌÂÛÔ‰¤ÚÌ·ÙÔ˜, ‰ÂÓ Û¯ËÌ·Ù›˙ÔÓÙ·È Î·ıfiÏÔ˘ ÔÈ ÌÂÛfiÓÂÊÚÔÈ Î·È ÔÈ ÌÂÙ¿ÓÂÊÚÔÈ (7). √ ·Ú·¿Óˆ Ê·ÈÓfiÙ˘Ô˜ ·ÓȯÓ‡ÂÙ·È Û ¤Ó· ÌÈÎÚfi ÔÛÔÛÙfi ÙˆÓ ÌÂÙ·ÏÏ·ÁÌ¤ÓˆÓ ÂÌ‚Ú‡ˆÓ Î·È ÚÔηÏÂ›Ù·È ·fi ‰È·Ù·Ú·¯¤˜ ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘, ÂÓÒ Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÂÌ‚Ú‡ˆÓ Âı·›ÓÂÈ ÚÈÓ ÙË ‰ËÌÈÔ˘ÚÁ›· ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘. ∏ ¯Ú‹ÛË ‰È·ÁÔÓȉȷÎÒÓ ˙ÒˆÓ Î·È ÔÓÙÈÎÒÓ Ì ÈÛÙÔÂȉÈ΋ ÌÂÙ·ÏÏ·Á‹ ÙÔ˘ ÁÔÓȉ›Ô˘ Lim1 Â¤ÙÚ„ ÙË ÌÂϤÙË Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ÁÔÓȉ›Ô˘ ·˘ÙÔ‡ Î·È Û ¿ÏÏ· ÛÙ¿‰È· Ù˘ ÓÂÊÚÈ΋˜ ·Ó¿Ù˘Í˘ (8). ∞fi ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ ÚԤ΢„ fiÙÈ Ú¿ÁÌ·ÙÈ Ë Lim1 ÂÌϤÎÂÙ·È fi¯È ÌfiÓÔ ÛÙË ‰ËÌÈÔ˘ÚÁ›· ·ÏÏ¿ Î·È ÛÙË ‰È·Ù‹ÚËÛË ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘, fiˆ˜ Î·È ÛÙË ¶·È‰È·ÙÚÈ΋ 2006;69:255-267

258

¶.¶. ¶¤ÙÚÔ˘

¶›Ó·Î·˜ 1. °ÔÓ›‰È· Ì ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ °ÔÓ›‰ÈÔ

ŒÎÊÚ·ÛË/ ∂ÓÙÔÈÛÌfi˜

∞. ªÂÙ·ÁÚ·ÊÈÎÔ› ·Ú¿ÁÔÓÙ˜** Pax2 ª¶, √∫, ∞™, ªª Ÿ¯È Û ÒÚÈÌÔ˘˜ ÓÂÊÚÒÓ˜ Eya1 ªª Lim1

¢ª

WT1 Six1

ªª ªª (Á‡Úˆ ·fi √∫)

Sall1 Foxc1 Emx2

ªª (Á‡Úˆ ·fi √∫), S, ¶√¢ MM OK, MM

Brn1 Lmx1b HNF1

∏, ∞™ ¶√¢ ∂Á™

Foxd1

™ÙÚ

Pod1

™ª, ¶√¢

µ. ∞˘ÍËÙÈÎÔ› ·Ú¿ÁÔÓÙ˜** GDNF ªª GDF11 √∫, ªª BMP4 ªª (Á‡Úˆ ·fi ª¶) BMP7

√∫, ªª

Slit2

ª¶, ªª

FGF8

™ª, ¡™

Wnt4 Wnt11 Grem1

ªª ∫ÔÚ˘Ê‹ √∫ ™ª (Á‡Úˆ ·fi √∫)

°. Àԉԯ›˜** Ret √∫ GFR·1 √∫, ªª Robo2 ªª, ª¶ (ÂÚÈÔ¯‹ ‰ËÌÈÔ˘ÚÁ›·˜ √∫) Sprouty1 √∫ ¢. ∂ÍˆÎ˘ÙÙ¿ÚȘ ÚˆÙ½Ó˜** HS2ST √∫, ªª (ÚÈÓ ‰È·ÊÔÚÔÔ›ËÛË ¡™) Nidogen1, ∂ÈıËÏȷΤ˜ µª LamininÁ1 Fras1, ∂ÈıËÏȷΤ˜ µª Frem1, Frem2 ∂. ÕÏϘ** Grip1 √∫, ÂÈı‹ÏÈ· ÓÂÊÚÒÓˆÓ Psn1, 2 ¡ÂÊÚÒÓ˜ Integrin ·8

ªª

º·ÈÓfiÙ˘Ô˜ (ÔÓÙÈÎfi˜)

∞ÓıÚÒÈÓÔ Û‡Ó‰ÚÔÌÔ

∞Ó·ÊÔÚ¿

√∫: ‰ÂÓ Â¿ÁÂÙ·È, ªª: ‰ÂÓ ‰È·ÊÔÚÔÔÈÂ›Ù·È √∫: ‰ÂÓ ‰ËÌÈÔ˘ÚÁ›ٷÈ, ªª: ‰ÂÓ Î·ıÔÚ›˙ÂÙ·È ª¶: ‰ÂÓ Û¯ËÌ·Ù›˙ÂÙ·È, ¢È·Ù·Ú·¯¤˜ ÛÙË ÌÔÚÊÔÔ›ËÛË ÙˆÓ ÓÂÊÚÒÓˆÓ ªª: ·fiÙˆÛË √∫: ‰ÂÓ ÂÈÛ‚¿ÏÏÂÈ Ï‹Úˆ˜ ÛÙÔ ªª (·fiÙˆÛË) √∫: ‰ÂÓ ÂÈÛ‚¿ÏÏÂÈ Ï‹Úˆ˜ ÛÙÔ ªª (·fiÙˆÛË) ¢ÈÏ‹ √∫, ¢ÈÏÔ› ÓÂÊÚÔ› √∫: ‰ÂÓ ‰È·ÎÏ·‰›˙ÂÙ·È, ªª: ·fiÙˆÛË ∏: ‰ÂÓ ÂÈÌË·ÓÂÙ·È ¢È·Ù·Ú·¯¤˜ ÛÙË µª ÙˆÓ ¡™ °Ï˘ÎÔ˙Ô˘Ú›·, ·ÌÈÓÔÍÔ˘Ú›· (Û‡Ó‰ÚÔÌÔ Fanconi) ªÂȈ̤ÓÔ˜ ·ÚÈıÌfi˜ ÓÂÊÚÒÓˆÓ, ¤ÎÙÔÔÈ, Û˘Á¯ˆÓÂ˘Ì¤ÓÔÈ ÓÂÊÚÔ› ªÂȈ̤ÓÔ˜ ·ÚÈıÌfi˜ ÓÂÊÚÒÓˆÓ ¶√¢: ‰ÂÓ ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È

Renal coloboma

74

Branchio-oto-renal (BOR)

75 8

WAGR*, Denys-Drash, Frasier 36 Branchio-oto-renal (BOR) 19 Townes-Brocks

21

Axenfeld-Rieger

24 32

Nail-patella

53 54 59 60 63

√∫: ‰ÂÓ ‰ËÌÈÔ˘ÚÁÂ›Ù·È Hirschsprung √∫: ‰ÂÓ ‰ËÌÈÔ˘ÚÁÂ›Ù·È BMP4+/-: ÀÔ-‰˘ÛÏ·Û›·, ˘‰ÚÔ˘ÚËÙ‹Ú·˜ ÀÔÏ·Û›·, ÌÂȈ̤ÓÔ˜ ·ÚÈıÌfi˜ ÓÂÊÚÒÓˆÓ, ∞™ ¶ÔÏÏ·Ϥ˜ √∫, ˘‰ÚÔ˘ÚËÙ‹Ú·˜, ÔÏ˘ÏÔ‚Ò‰ÂȘ ÓÂÊÚÔ› ªÂȈ̤ÓË: ‰È·ÎÏ¿‰ˆÛË √∫, ‰È·ÊÔÚÔÔ›ËÛË ¡™ ªª: ‰ÂÓ ÂÈıËÏÈÔÔÈ›ٷÈ, ˘ÔÏ·Û›· √∫: ÌÂȈ̤ÓË ‰È·ÎÏ¿‰ˆÛË, ˘ÔÏ·Û›· √∫: ‰ËÌÈÔ˘ÚÁÂ›Ù·È ·ÏÏ¿ ‰ÂÓ ‰È·ÎÏ·‰›˙ÂÙ·È

12-14 11 26

√∫: ‰ÂÓ ‰ËÌÈÔ˘ÚÁÂ›Ù·È √∫: ‰ÂÓ ‰ËÌÈÔ˘ÚÁÂ›Ù·È ¶ÔÏÏ·Ϥ˜ √∫, ˘‰ÚÔ˘ÚËÙ‹Ú·˜, ÔÏ˘ÏÔ‚Ò‰ÂȘ ÓÂÊÚÔ› ¶ÔÏÏ·Ϥ˜ √∫, Ô˘ÚËÙ‹Ú˜

15 17, 18 23

¢È·Ù·Ú·¯¤˜ Û ‰È·ÎÏ¿‰ˆÛË √∫, Û˘Ì‡ÎÓˆÛË ªª ª¶: ‰ÂÓ ÂÈÌË·ÓÂÙ·È, ·ÁÂÓÂÛ›·

65

76 23 45 41 31 22

25

66

√∫: ‰ËÌÈÔ˘ÚÁ›ٷÈ, ªª: ‰ÂÓ ‰È·ÊÔÚÔÔÈÂ›Ù·È ∞fiÙˆÛË, ·ÁÂÓÂÛ›·

Fraser

68, 70, 72, 73

√∫: ‰ËÌÈÔ˘ÚÁ›ٷÈ, ªª: ‰ÂÓ ‰È·ÊÔÚÔÔÈÂ›Ù·È ¢È·ÊÔÚÔÔ›ËÛË ¡™ ÛÙ·Ì·Ù¿ ÛÙÔ ÛÙ¿‰ÈÔ ÙˆÓ S ¢È·Ù·Ú·¯¤˜ Û ‰ËÌÈÔ˘ÚÁ›· ÂÈÌ‹Î˘ÓÛË √∫, Û˘Ì‡ÎÓˆÛË ªª

Fraser

71

Alzheimer’s

58 67

∞™: Õˆ ÛˆÏËÓ¿ÚÈ·, ∞™: ∞ıÚÔÈÛÙÈο ÛˆÏËÓ¿ÚÈ·, µª: µ·ÛÈΤ˜ ÌÂÌ‚Ú¿Ó˜, ¢ª: ¢È¿ÌÂÛÔ ÌÂÛfi‰ÂÚÌ·, ∂Á™: ∂ÁÁ‡˜ ÛˆÏËÓ¿ÚÈ·, ∏: ∞Á·ÏË ÙÔ˘ Henle, ªª: ªÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì·, ª¶: ªÂÛÔÓÂÊÚÈÎfi˜ fiÚÔ˜, ¡™: ¡ÂÊÚÈο ÛÂÈÚ¿Ì·Ù·, √∫: Ô˘ÚËÙËÚÈ΋ ηٷ‚ÔÏ‹. ¶√¢: ¶Ô‰Ô·ÙÙ·Ú·, ™ª: ™˘Ì˘Îӈ̤ӷ ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú·, ™ÙÚ: ™ÙÚÒÌ·, S: ™ÈÁÌÔÂȉ‹ ÛˆÏËÓ¿ÚÈ· *Wilms’ tumor - Aniridia - genitourinary abnormalities - mental retardation **∞ӷʤÚÂÙ·È ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ ÚˆÙÂ˚ÓÒÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡ÓÙ·È ·fi Ù· ·Ó·ÁÚ·ÊfiÌÂÓ· ÁÔÓ›‰È·

¶·È‰È·ÙÚÈ΋ 2006;69:255-267

259

°ÔÓ›‰È· ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ

‰ËÌÈÔ˘ÚÁ›· Î·È ‰È·ÎÏ¿‰ˆÛË Ù˘ √∫, ηıÒ˜ Î·È ÛÙË ÌÔÚÊÔÔ›ËÛË (patterning) ÙˆÓ ÂÈıËÏ›ˆÓ ÙˆÓ ÓÂÊÚÒÓˆÓ. ∂ͤ¯ÔÓÙ· ÚfiÏÔ ÛÙË ‰È·‰Èηۛ· Ù˘ ÓÂÊÚÔÁ¤ÓÂÛ˘ Ê·›ÓÂÙ·È Ó· ·›˙Ô˘Ó ÔÈ ·Ú¿ÁÔÓÙ˜ Pax2 Î·È Pax8, ÔÈ ÔÔ›ÔÈ ·Ó‹ÎÔ˘Ó ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ paired domain ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ. ∏ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ Pax2 ·Ú¯›˙ÂÈ ·fi ÙÔ ÛÙ¿‰ÈÔ ÙÔ˘ ÚfiÓÂÊÚÔ˘. øÛÙfiÛÔ, Û ÔÓÙ›ÎÈ· Ì ¤ÏÏÂÈ„Ë Ù˘ Pax2, Ô ÌÂÛÔÓÂÊÚÈÎfi˜ fiÚÔ˜ Û¯ËÌ·Ù›˙ÂÙ·È, ·ÏÏ¿ ÂÎÊ˘Ï›˙ÂÙ·È Ôχ ÓˆÚ›˜, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌË Û¯ËÌ·Ù›˙ÔÓÙ·È ÙfiÛÔ Ô ÌÂÛfiÓÂÊÚÔ˜ fiÛÔ Î·È Ô ÌÂÙ¿ÓÂÊÚÔ˜ (9). ∂ӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙ÂÈ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ, ·ÚfiÏÔ Ô˘ Ë ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÁÔÓȉ›Ô˘ Pax8 ‰ÂÓ ÚÔηÏ› ‚Ï¿‚˜ ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ, ÂÓÙÔ‡ÙÔȘ, Û ‰ÈÏ¿ ÌÂÙ·ÏÏ·Á̤ӷ ˙Ò· Pax2-/-/Pax8-/-** ‰ÂÓ Û¯ËÌ·Ù›˙ÂÙ·È Ô‡ÙÂ Ô ÚfiÓÂÊÚÔ˜ (10). ∏ ·Ú·¿Óˆ ·ÔÙÂÏ› ÙË ÌÔÓ·‰È΋ ÁÓˆÛÙ‹ ÌÂÙ¿ÏÏ·ÍË Ë ÔÔ›· ÂËÚ¿˙ÂÈ ÙËÓ ÓÂÊÚÔÁ¤ÓÂÛË ÛÙÔ ÛÙ¿‰ÈÔ ÙÔ˘ ÚfiÓÂÊÚÔ˘. ¶Èı·Ófi˜ ÚfiÏÔ˜ ÛÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ¤¯ÂÈ Â›Û˘ ·Ô‰Ôı› Î·È ÛÙËÓ ÂÎÎÚÈÓfiÌÂÓË ÚˆÙ½ÓË GDF11 (Growth differentiation factor 11), Ë ÔÔ›· ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ Transforming growth factor-‚ (TGF-‚) ·Ú·ÁfiÓÙˆÓ (11).

∂·ÁˆÁ‹ Ù˘ Ô˘ÚËÙËÚÈ΋˜ ηٷ‚ÔÏ‹˜ ∆Ô Î‡ÚÈÔ ÛËÌ·ÙÔ‰ÔÙÈÎfi ÌfiÚÈÔ (signaling molecule) ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ Ô˘ Â›Ó·È ˘‡ı˘ÓÔ ÁÈ· ÙËÓ Â·ÁˆÁ‹ Ù˘ Ô˘ÚËÙËÚÈ΋˜ ηٷ‚ÔÏ‹˜ (√∫) Â›Ó·È Ô ·Ú¿ÁÔÓÙ·˜ GDNF (Glial cell-derived neurotrophic factor), Ô ÔÔ›Ô˜ ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ TGF-‚ ÚˆÙÂ˚ÓÒÓ. ∞˘Ùfi˜ ÂÎÎÚ›ÓÂÙ·È ·fi ÙÔ Î·ıÔÚÈṲ̂ÓÔ ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì· Î·È ÚÔÛ‰¤ÓÂÙ·È Û ¤Ó· Û‡ÌÏÔÎÔ ˘Ô‰Ô¯¤ˆÓ ·ÔÙÂÏÔ‡ÌÂÓÔ ·fi ÙËÓ ÎÈÓ¿ÛË Ù˘ÚÔÛ›Ó˘ Ret Î·È ÙÔ Û˘Ó˘Ô‰Ô¯¤· GFR·1, Ô˘ ÂÓÙÔ›˙ÂÙ·È ÛÙ· ÂÈıËÏȷο ·ÙÙ·Ú· ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘. ∏ ÛËÌ·Û›· Ù˘ ÛËÌ·ÙÔ‰fiÙËÛ˘ Ù˘ GDNF ÛÙË ÈÛÙÔÁ¤ÓÂÛË ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘ ‰È·Ê·›ÓÂÙ·È ·fi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÙfiÛÔ Ë ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ›‰ÈÔ˘ ÙÔ˘ GDNF (12-14) ·ÏÏ¿ Î·È ÙˆÓ Ret (15,16) Î·È GFRa1 (17,18) Ô‰ËÁ› Û ·ÁÂÓÂÛ›· ÙˆÓ ÓÂÊÚÒÓ. ¶·ÚfiÏ· ·˘Ù¿, Ê·›ÓÂÙ·È fiÙÈ Ë GDNF ‰ÂÓ ·ÔÙÂÏ› ÙÔ ÌÔÓ·‰ÈÎfi ÛËÌ·ÙÔ‰ÔÙÈÎfi ÌfiÚÈÔ ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜. ¶ÂÚ›Ô˘ ÛÙÔ ¤Ó· ÙÚ›ÙÔ ÙˆÓ GDNF Î·È ÙˆÓ Ret

ÌÂÙ·ÏÏ·ÁÌ¤ÓˆÓ ˙ÒˆÓ ÂÈÙ˘Á¯¿ÓÂÙ·È Ë Â·ÁˆÁ‹ Ù˘ O∫ Î·È Ë ‰ËÌÈÔ˘ÚÁ›· ‰˘ÛÏ·ÛÙÈÎÒÓ ÓÂÊÚÒÓ (15,16). ∂Ӊ›ÍÂȘ Û¯ÂÙÈο Ì ÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Â·ÁˆÁ‹˜ Ù˘ √∫ ¤¯Ô˘Ó ÚÔ·„ÂÈ ·fi ÙËÓ ·ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Six1 (19,20) Î·È Sall1 (21). ™˘ÁÎÂÎÚÈ̤ӷ, Û ÔÓÙ›ÎÈ· Ì ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ·ÓÙ›ÛÙÔȯ· ÁÔÓ›‰È· Six1 ‹ Sall1, ÙÔ ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì· Ê·›ÓÂÙ·È Ó· ηıÔÚ›˙ÂÙ·È Î·ÓÔÓÈο, ÌÔÏÔÓfiÙÈ Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÌÂȈ̤ÓÔ˜. ∫·Ù¿ Û˘Ó¤ÂÈ· Î·È ÛÙȘ ‰‡Ô ÂÚÈÙÒÛÂȘ ·Ú·ÙËÚÂ›Ù·È ·ÁÂÓÂÛ›· ‹ ˘ÔÏ·Û›· ÙˆÓ ÓÂÊÚÒÓ, Ô˘ ÔÊ›ÏÂÙ·È ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë √∫ ‰ÂÓ ÂÈÛ‚¿ÏÏÂÈ Ï‹Úˆ˜ ÛÙÔ ÌÂÛ¤Á¯˘Ì·, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ‰È·‰Èηۛ·˜ Ù˘ ·fiÙˆÛ˘ ÛÙÔ ÙÂÏÂ˘Ù·›Ô. ∞˘Ùfi ˘Ô‰ÂÈÎÓ‡ÂÈ fiÙÈ ÙÔ Ì¤ÁÂıÔ˜ ÙÔ˘ ηıÔÚÈṲ̂ÓÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ·›˙ÂÈ Èı·ÓfiÓ Î·ıÔÚÈÛÙÈÎfi ÚfiÏÔ ÛÙË ‰ËÌÈÔ˘ÚÁ›· Ù˘ √∫. º·ÈÓÔÙ˘ÈΤ˜ ‰È·Ù·Ú·¯¤˜ ·ÚfiÌÔȘ Ì ·˘Ù¤˜ ÙˆÓ Six1 Î·È Sall1 ÌÂÙ·ÏÏ·ÁÌ¤ÓˆÓ ÔÓÙÈÎÒÓ ÚÔ·ÙÔ˘Ó ·fi ÙËÓ ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÁÔÓȉ›Ô˘ Grem1, ÙÔ ÔÔ›Ô ÂÎÊÚ¿˙ÂÙ·È ÛÙÔ Ô˘Ú·›Ô ¿ÎÚÔ ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘ Î·È ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ (22). ∆Ô Grem1 Έ‰ÈÎÔÔÈ› ÙËÓ ÚˆÙ½ÓË Gremlin, Ë ÔÔ›· ·ÓÙ·ÁˆÓ›˙ÂÙ·È ÙËÓ ‰Ú¿ÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ BMP (Bone Morphogenic Protein), ΢ڛˆ˜ Ù˘ BMP2 Î·È BMP4 (‚Ï. ·Ú·Î¿Ùˆ). √ Ê·ÈÓfiÙ˘Ô˜ ÛÙÔ˘˜ ÓÂÊÚÔ‡˜ ÙˆÓ Grem1-/- ÔÓÙÈÎÒÓ Î·Ù·‰ÂÈÎÓ‡ÂÈ ÙË ÛËÌ·Û›· ÙÔ˘ ·ÓÙ·ÁˆÓÈÛÌÔ‡ Ù˘ ÛËÌ·ÙÔ‰ÔÙÈ΋˜ ‰Ú¿Û˘ ÙˆÓ BMP ·fi ÙË Gremlin ÛÙË ‰ËÌÈÔ˘ÚÁ›· Ù˘ √∫. ™ËÌ·ÓÙÈÎfi˜ ÁÈ· ÙËÓ Â·ÁˆÁ‹ Ù˘ √∫ Â›Ó·È Â›Û˘ Ô ÚfiÏÔ˜ ÙˆÓ ÂÎÎÚÈÓfiÌÂÓˆÓ ÚˆÙÂ˚ÓÒÓ SLIT Î·È ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘˜ ROBO. ∆Ô ÁÔÓ›‰ÈÔ Slit2 ÂÎÊÚ¿˙ÂÙ·È Î·Ù¿ Ì‹ÎÔ˜ ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘, ·ÏÏ¿ Î·È ¤ÓÙÔÓ· ÛÙÔ ‰È¿ÌÂÛÔ ÌÂÛfi‰ÂÚÌ·, ·ÎÚÈ‚Ò˜ ÎÂÊ·ÏÈÎfiÙÂÚ· Ù˘ ÂÚÈÔ¯‹˜ ¤ÎÊÚ·Û˘ ÙÔ˘ GDNF. ∏ ·ÂÓÂÚÁÔÔ›ËÛË ÙfiÛÔ ÙÔ˘ Slit2 fiÛÔ Î·È ÙÔ˘ Robo2 ÚÔηÏ› ·ÚfiÌÔÈÔ Ê·ÈÓfiÙ˘Ô, Ô ÔÔ›Ô˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙÔÓ Û¯ËÌ·ÙÈÛÌfi ÔÏÏ·ÏÒÓ √∫, ÔÈ Ôԛ˜ ÂÎʇÔÓÙ·È ÎÂÊ·ÏÈÎfiÙÂÚ· ÙÔ˘ ηÓÔÓÈÎÔ‡ ÛËÌ›Ԣ ‰ËÌÈÔ˘ÚÁ›·˜ Ù˘ √∫ (23). ™Â ÌÔÚÈ·Îfi Â›‰Ô, Ë ¤ÏÏÂÈ„Ë ÙˆÓ Slit2 Î·È Robo2 ÚÔηÏ› Â¤ÎÙ·ÛË Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ GDNF ÎÂÊ·ÏÈÎfiÙÂÚ·, Ô˘ ÛËÌ·›ÓÂÈ fiÙÈ ÙÔ Û‡ÛÙËÌ· Slit2/Robo2 Ê˘ÛÈÔÏÔÁÈο ÔÚÈÔıÂÙ› ÙËÓ ÂÚÈÔ¯‹ ¤ÎÊÚ·Û˘ ÙÔ˘ GDNF ÛÙÔ ÛˆÛÙfi ÛËÌÂ›Ô ÙÔ˘

* √ÓfiÌ·Ù· Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ÚˆÙ½Ó˜ ·Ó·ÁÚ¿ÊÔÓÙ·È Ì ·Ï‹, ÂÓÒ ÔÓfiÌ·Ù· ÁÔÓȉ›ˆÓ Ì Ï¿ÁÈ· ÁÚ·Ê‹. ** √ Û˘Ì‚ÔÏÈÛÌfi˜ -/- ÂÚÈÁÚ¿ÊÂÈ ÙËÓ ‡·ÚÍË Ù˘ ÌÂÙ¿ÏÏ·Í˘ Î·È ÛÙ· ‰‡Ô ·ÓÙ›ÁÚ·Ê· ÙÔ˘ ·ÓÙ›ÛÙÔÈ¯Ô˘ ÁÔÓȉ›Ô˘. ¶·È‰È·ÙÚÈ΋ 2006;69:255-267

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‰È·Ì¤ÛÔ˘ ÌÂÛÔ‰¤ÚÌ·ÙÔ˜. ™ÙÔÓ Î·ıÔÚÈÛÌfi Ù˘ ÂÚÈÔ¯‹˜ ¤ÎÊÚ·Û˘ ÙÔ˘ GDNF ÂÌϤÎÂÙ·È Î·È Ô ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Foxc1. Ÿˆ˜ Î·È Ì ÙȘ Slit2/Robo2, Ë ¤ÏÏÂÈ„Ë Ù˘ Foxc1 Û ÌÂÙ·ÏÏ·Á̤ӷ ÔÓÙ›ÎÈ· ÚÔηÏ› Â¤ÎÙ·ÛË Ù˘ ÂÚÈÔ¯‹˜ ¤ÎÊÚ·Û˘ ÙÔ˘ GDNF ÎÂÊ·ÏÈÎfiÙÂÚ·, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ¤ÎÙÔË Â·ÁˆÁ‹ ÚfiÛıÂÙ˘ √∫ Î·È ÙË ‰ËÌÈÔ˘ÚÁ›· ‰ÈÏÒÓ ÓÂÊÚÒÓ (24). ƒ˘ıÌÈÛÙÈÎfi ÚfiÏÔ ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ GDNF Ê·›ÓÂÙ·È Â›Û˘ Ó· ·›˙ÂÈ Ô ·Ú¿ÁÔÓÙ·˜ Sprouty-1, Ô ÔÔ›Ô˜ ‰Ú· Û·Ó ·ÓÙ·ÁˆÓÈÛÙ‹˜ ˘Ô‰Ô¯¤ˆÓ ÎÈÓ¿Û˘ Ù˘ÚÔÛ›Ó˘. ∞ÓÂ¿ÚÎÂÈ· ÁÈ· ÙËÓ ·Ú·¿Óˆ ÚˆÙ½ÓË Ô‰ËÁ› ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÔÏÏ·ÏÒÓ √∫ ÏfiÁˆ ·˘ÍË̤Ó˘ ·fiÎÚÈÛ˘ ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘ ÛÙËÓ GDNF (25). ¶Ú¿ÁÌ·ÙÈ, Ô ·Ú·¿Óˆ Ê·ÈÓfiÙ˘Ô˜ ‰ÈÔÚıÒÓÂÙ·È ÛÙËÓ ·ÚÔ˘Û›· ÌÂȈ̤Ó˘ ‰fiÛ˘ GDNF Û ÂÙÂÚfi˙˘Á· GDNF ÌÂÙ·ÏÏ·Á̤ӷ ˙Ò·. ∞fi ÙȘ Ê·ÈÓÔÙ˘ÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘ ÚÔ·ÙÔ˘Ó ·fi ÙȘ ÈÔ ¿Óˆ ÌÂÙ·ÏÏ¿ÍÂȘ ‰È·Ê·›ÓÂÙ·È Ë ÛËÌ·Û›· Ù˘ ÛˆÛÙ‹˜ Ú‡ıÌÈÛ˘ ÙfiÛÔ Ù˘ ÔÛfiÙËÙ·˜, fiÛÔ Î·È Ù˘ ÂÚÈÔ¯‹˜ ¤ÎÊÚ·Û˘ ÙÔ˘ GDNF ÛÙȘ ‰È·‰Èηۛ˜ ηıÔÚÈÛÌÔ‡ ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ Î·È Â·ÁˆÁ‹˜ Ù˘ √∫. ™Â ·ÓÙ›ıÂÛË Ì ÙË GDNF, Ë ÔÔ›· ‰Ú· ıÂÙÈο ÛÙË ‰ËÌÈÔ˘ÚÁ›· Ù˘ √∫, ÙÔ ÛËÌ·ÙÔ‰ÔÙÈÎfi ÌfiÚÈÔ BMP4, ÙÔ ÔÔ›Ô ·Ú¿ÁÂÙ·È ·fi ÙÔ ÌÂÛ¤Á¯˘Ì· Á‡Úˆ ·fi ÙÔÓ ÌÂÛÔÓÂÊÚÈÎfi fiÚÔ, ÂËÚ¿˙ÂÈ ·ÚÓËÙÈο ÙȘ ·Ú·¿Óˆ ‰È·‰Èηۛ˜ (26). √ Û˘Ó‰˘·ÛÌfi˜ ıÂÙÈ΋˜ Î·È ·ÚÓËÙÈ΋˜ ÛËÌ·ÙÔ‰ÔÙÈ΋˜ ‰Ú¿Û˘ ·fi ÙÔ ÌÂÛ¤Á¯˘Ì· ÛÙÔ ÂÈı‹ÏÈÔ ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘ ÈÛÙ‡ÂÙ·È fiÙÈ ÂÌÔ‰›˙ÂÈ ÙËÓ ÚfiˆÚË Î·È ¤ÎÙÔË ‰ËÌÈÔ˘ÚÁ›· Ù˘ √∫, ‰È·ÛÊ·Ï›˙ÔÓÙ·˜ Ù·˘Ùfi¯ÚÔÓ· ÙËÓ Â·ÁˆÁ‹ Ù˘ ÛÙÔ ÛˆÛÙfi ÛËÌ›Ô, ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘ ‰›Ï· ·fi ÙÔ ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì·.

∞ÔÊ˘Á‹ ·fiÙˆÛ˘ Î·È Î˘ÙÙ·ÚÈÎfi˜ ÔÏÏ·Ï·ÛÈ·ÛÌfi˜ ÛÙÔ Î·ıÔÚÈṲ̂ÓÔ ÌÂÛ¤Á¯˘Ì· ¶ÂÈÚ¿Ì·Ù· Û in vitro ηÏÏȤÚÁÂȘ ÓÂÊÚÒÓ ÔÓÙÈÎÔ‡ ηıÒ˜ Î·È Û ÙÚˆÎÙÈο, ¤‰ÂÈÍ·Ó fiÙÈ ÛÙËÓ ÂÚ›ÙˆÛË ·ÔÙ˘¯›·˜ Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ Ù˘ √∫ Ù· ·ÙÙ·Ú· ÙÔ˘ ηıÔÚÈṲ̂ÓÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ Â›Ó·È ÚÔÁÚ·ÌÌ·ÙÈṲ̂ӷ Ó· ı·Ó·ÙˆıÔ‡Ó ·ÎÔÏÔ˘ıÒÓÙ·˜ ‰È·‰Èηۛ˜ ·fiÙˆÛ˘. ∂Ô̤ӈ˜, Ë ÂÈ‚›ˆÛË ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙËÓ ‰ËÌÈÔ˘ÚÁ›· Ù˘ √∫ Â›Ó·È ··Ú·›ÙËÙË ÚÔ¸fiıÂÛË ÁÈ· ÙËÓ ÔÌ·Ï‹ ÌÔÚÊÔÁ¤ÓÂÛË ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘. ¶Ú¿ÁÌ·ÙÈ, ÛÙËÓ √∫ ÂÎÊÚ¿˙Ô¶·È‰È·ÙÚÈ΋ 2006;69:255-267

ÓÙ·È ÛËÌ·ÙÔ‰ÔÙÈο ÌfiÚÈ· Ù· ÔÔ›· ·ÔÙÚ¤Ô˘Ó ÙÔÓ ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓÔ Î˘ÙÙ·ÚÈÎfi ı¿Ó·ÙÔ ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜. ∆¤ÙÔÈ· ·ÓÙÈ-·ÔÙˆÙÈ΋ ‰Ú¿ÛË ¤¯ÂÈ ‰Âȯı› ÁÈ· ÙÔÓ ·Ú¿ÁÔÓÙ· EGF (Epidermal growth factor) (27). øÛÙfiÛÔ, Ë ·ÔÙÚÔ‹ Ù˘ ·fiÙˆÛ˘ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ‰ÂÓ Â›Ó·È ·fi ÌfiÓË Ù˘ ·ÚÎÂÙ‹ ÁÈ· Ó· ˘ÔÛÙËÚ›ÍÂÈ ÙËÓ ÌÂÙ¤ÂÈÙ· ·Ó¿Ù˘ÍË ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘. °È’ ·˘ÙfiÓ ÙÔ ÛÎÔfi ··ÈÙÂ›Ù·È Ë ·ÚÔ˘Û›· ·Ú·ÁfiÓÙˆÓ ÔÈ ÔÔ›ÔÈ ‰ÈÂÁ›ÚÔ˘Ó ÙÔÓ Î˘ÙÙ·ÚÈÎfi ÔÏÏ·Ï·ÛÈ·ÛÌfi. °ÓˆÛÙ¿ ÛËÌ·ÙÔ‰ÔÙÈο ÌfiÚÈ· Ù· ÔÔ›· Â¿ÁÔ˘Ó ÙÔÓ Î˘ÙÙ·ÚÈÎfi ÔÏÏ·Ï·ÛÈ·ÛÌfi ÛÙÔ ÌÂÛ¤Á¯˘Ì· Â›Ó·È ÔÈ ·Ú¿ÁÔÓÙ˜ BMP-4 Î·È BMP-7, Ô˘ ÂÎÊÚ¿˙ÔÓÙ·È Î˘Ú›ˆ˜ ·fi Ù· ÂÈı‹ÏÈ· ÙˆÓ ‰È·ÊÔÚÔÔÈÔ‡ÌÂÓˆÓ ÓÂÊÚÒÓˆÓ (26). ∏ BMP-7 Û˘ÁÎÂÎÚÈ̤ӷ, ˘ÔÛÙËÚ›˙ÂÈ ÙfiÛÔ ÙËÓ ÂÈ‚›ˆÛË fiÛÔ Î·È ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. ¶·ÚfiÌÔÈ· Ê·›ÓÂÙ·È Â›Û˘ Ó· Â›Ó·È Ë ‰Ú¿ÛË ÙÔ˘ ÛËÌ·ÙÔ‰ÔÙÈÎÔ‡ ÌÔÚ›Ô˘ Fibroblast growth factor (FGF)-2 (28).

¢È·ÎÏ¿‰ˆÛË (branching) Ù˘ Ô˘ÚËÙËÚÈ΋˜ ηٷ‚ÔÏ‹˜ ∆Ô Î·ıÔÚÈṲ̂ÓÔ ÌÂÛ¤Á¯˘Ì· ·Ú¿ÁÂÈ ÌÈ· ÛÂÈÚ¿ ·fi ÛËÌ·ÙÔ‰ÔÙÈο ÌfiÚÈ·, Ù· ÔÔ›· ‰ÚÔ˘Ó ÛÙËÓ √∫ Î·È Â¿ÁÔ˘Ó ÌÈ· ÛÙÂÚÂfiÙ˘Ë ·ÎÔÏÔ˘ı›· ÂÈÌË·ÓÛÂˆÓ Î·È ‰È·ÎÏ·‰ÒÛÂˆÓ ÛÙÔ ÂÈı‹ÏÈÔ, ÔÈ Ôԛ˜ Ô‰ËÁÔ‡Ó ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ÙˆÓ ·ıÚÔÈÛÙÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ. ¶ÈÛÙ‡ÂÙ·È fiÙÈ ÙÔ ÚfiÙ˘Ô Ù˘ ‰È·ÎÏ¿‰ˆÛ˘ ÙÔ˘ ÂÈıËÏ›Ô˘ Ù˘ √∫ ηıÔÚ›˙ÂÙ·È ·fi ÙÔÓ Û˘Ó‰˘·ÛÌfi ÛËÌ¿ÙˆÓ Ù· ÔÔ›· ÚÔηÏÔ‡Ó Â›Ù ÙËÓ ·ÔÈÎÔ‰fiÌËÛË, ›Ù ÙË ÛÙ·ıÂÚÔÔ›ËÛË Ù˘ ÂÍˆÎ˘ÙÙ¿ÚÈ·˜ ‡Ï˘ Á‡Úˆ ·fi ÙÔ ÂÈı‹ÏÈÔ Î·È ·ÓÙ›ÛÙÔȯ· ÚÔ¿ÁÔ˘Ó ‹ ÂÌÔ‰›˙Ô˘Ó ÙËÓ ‰È·ÎÏ¿‰ˆÛ‹ ÙÔ˘. √ ·Ú¿ÁÔÓÙ·˜ GDNF, Ô ÔÔ›Ô˜, fiˆ˜ ÚԷӷʤÚıËÎÂ, Â›Ó·È ··Ú·›ÙËÙÔ˜ ÁÈ· ÙËÓ Â·ÁˆÁ‹ Ù˘ √∫ ·fi ÙÔ ÌÂÛÔÓÂÊÚÈÎfi fiÚÔ, ÂÍ·ÎÔÏÔ˘ı› Ó· Â›Ó·È ·Ó·Áη›Ô˜ Î·È ÛÙË ‰È·‰Èηۛ· Ù˘ ‰È·ÎÏ¿‰ˆÛ˘ ÙÔ˘ ÂÈıËÏ›Ô˘. ∞˘Ùfi ÚÔ·ÙÂÈ ·fi ÂÈÚ¿Ì·Ù· Û ÈÛÙÔηÏÏȤÚÁÂȘ ÓÂÊÚÒÓ ÛÙ· ÔÔ›· ηٷÛÙ¤ÏÏÔÓÙ·˜ ÙË ‰Ú¿ÛË Ù˘ GDNF ·ÚÂÌÔ‰›˙ÂÙ·È Ë ‰È·ÎÏ¿‰ˆÛË, ÂÓÒ ·ÓÙÈı¤Ùˆ˜ ÚÔ¿ÁÂÙ·È Ì ÙËÓ ÚÔÛı‹ÎË Â͈ÁÂÓÔ‡˜ GDNF (29,30). ÀÔÏ·Û›· ÙˆÓ ÓÂÊÚÒÓ ·Ú·ÙËÚÂ›Ù·È ÛÂ Û˘Óı‹Î˜ ¤ÏÏÂȄ˘ Ù˘ ÂÎÎÚÈÓfiÌÂÓ˘ ÚˆÙ½Ó˘ Wnt11, ·ÔηχÙÔÓÙ·˜ ÙÔÓ ÚfiÏÔ ÙÔ˘ ·Ú·¿Óˆ ·Ú¿ÁÔÓÙ· ÛÙË ‰È·‰Èηۛ· Ù˘

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°ÔÓ›‰È· ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ

‰È·ÎÏ¿‰ˆÛ˘ ÙÔ˘ ÂÈıËÏ›Ô˘. ∆Ô ÁÔÓ›‰ÈÔ Wnt11 ÂÎÊÚ¿˙ÂÙ·È ÛÙËÓ ÎÔÚ˘Ê‹ Ù˘ √∫ Î·È Ë ·ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘ ÚÔηÏ› Ì›ˆÛË ÙˆÓ ÂÈ¤‰ˆÓ ¤ÎÊÚ·Û˘ ÙÔ˘ GDNF (31). ∂ӉȷʤÚÔ˘Û˜ ÂӉ›ÍÂȘ Û¯ÂÙÈο Ì ÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ú‡ıÌÈÛ˘ ‰È·ÊfiÚˆÓ ·Ú·ÁfiÓÙˆÓ ÌÂÙ¿ ÙËÓ Â·ÁˆÁ‹ Ù˘ √∫ ¤¯Ô˘Ó ÚÔ·„ÂÈ ·fi ÙË ÛÙÔ¯Â˘Ì¤ÓË ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÁÔÓȉ›Ô˘ Emx2 ÛÙÔÓ ÔÓÙÈÎfi, ÔÌfiÏÔÁÔ˘ ÙÔ˘ ÔÌÔÈÔÙÈÎÔ‡ ÁÔÓȉ›Ô˘ empty spiracles Ù˘ ‰ÚÔÛfiÊÈÏ·˜. ™˘ÁÎÂÎÚÈ̤ӷ, ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ¤ÏÏÂȄ˘ Ù˘ Emx2 ÛÙÔÓ ÔÓÙÈÎfi Ë √∫ Û¯ËÌ·Ù›˙ÂÙ·È Î·ÓÔÓÈο ·ÏÏ¿ ‰ÂÓ ‰È·ÎÏ·‰›˙ÂÙ·È Î·ıfiÏÔ˘, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ì˯·ÓÈÛÌÒÓ ·fiÙˆÛ˘ ÛÙÔ ÌÂÛ¤Á¯˘Ì·. √È ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘ Ô‰ËÁÔ‡Ó ÛÙÔÓ ·Ú·¿Óˆ Ê·ÈÓfiÙ˘Ô ÈÛÙ‡ÂÙ·È fiÙÈ Â›Ó·È Ë ‰Ú·ÛÙÈ΋ Ì›ˆÛË ÙˆÓ ·Ú¯Èο Ê˘ÛÈÔÏÔÁÈÎÒÓ ÂÈ¤‰ˆÓ ¤ÎÊÚ·Û˘ ÙˆÓ ÁÔÓȉ›ˆÓ Pax2, GDNF Î·È Ret (32). ∂ÈϤÔÓ ÛËÌ·ÙÔ‰ÔÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙË ‰È·‰Èηۛ· Ù˘ ‰È·ÎÏ¿‰ˆÛ˘ Ù˘ √∫ Â›Ó·È Ô HGF (hepatocyte growth factor), Ô ÔÔ›Ô˜ ÙËÓ ÚÔ¿ÁÂÈ (33), ÂÓÒ ¿ÏÏ· ÌfiÚÈ· fiˆ˜ Ë BMP-2 (34), BMP-4 (26) Î·È TGF‚ (35) ‰ÚÔ˘Ó Î·Ù·ÛÙ·ÏÙÈο ÛÙËÓ ·Ú·¿Óˆ ‰È·‰Èηۛ·. ∂ӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙ÂÈ Ô ·Ú¿ÁÔÓÙ·˜ BMP-7, Ô ÔÔ›Ô˜ ÂÎÎÚ›ÓÂÙ·È Û ̤ÙÚȘ ÔÛfiÙËÙ˜ ·fi ÙÔ ÌÂÛ¤Á¯˘Ì· Î·È Û ÌÂÁ·Ï‡ÙÂÚ˜ ·fi ÙÔ ‰È·ÎÏ·‰È˙fiÌÂÓÔ ÂÈı‹ÏÈÔ. ÷ÌËÏ¿ Â›‰· BMP-7 Ê·›ÓÂÙ·È Ó· ÚÔ¿ÁÔ˘Ó ÙË ‰È·ÎÏ¿‰ˆÛË Ù˘ √∫, ÂÓÒ ˘„ËÏfiÙÂÚ· ÙËÓ ÂÌÔ‰›˙Ô˘Ó (34). √ Û˘ÁÎÂÎÚÈ̤ÓÔ˜ Ì˯·ÓÈÛÌfi˜ ηıÒ˜ Î·È Ô Û˘Ó‰˘·ÛÌfi˜ ıÂÙÈ΋˜ Î·È ·ÚÓËÙÈ΋˜ ÛËÌ·ÙÔ‰fiÙËÛ˘ ÁÂÓÈÎfiÙÂÚ·, ÂÈÙ˘Á¯¿ÓÂÈ ÙËÓ Î·Ù·ÛÙÔÏ‹ ‹ ÙËÓ ÂÓ›Û¯˘ÛË Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ Ó¤ˆÓ ‰È·ÎÏ·‰ÒÛÂˆÓ Û ÂÚÈÔ¯¤˜ ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ÏÔ‡ÛȘ ‹ ÊÙˆ¯¤˜ Û ÂÈıËÏȷΤ˜ ‰È·ÎÏ·‰ÒÛÂȘ ·ÓÙ›ÛÙÔȯ·. ŒÙÛÈ, ÂÍ·ÛÊ·Ï›˙ÂÙ·È Ë ÔÌÔÈfiÌÔÚÊË Î·Ù·ÓÔÌ‹ ÙˆÓ ‰È·ÎÏ·‰ÒÛÂˆÓ Ù˘ √∫ Û fiÏË ÙËÓ ¤ÎÙ·ÛË ÙÔ˘ ÌÂÙ·ÓÂÊÚÈÎÔ‡ ÌÂÛÂÁ¯‡Ì·ÙÔ˜.

¢ËÌÈÔ˘ÚÁ›· ÙˆÓ ÓÂÊÚÒÓˆÓ ∏ ‰È·‰Èηۛ· Ù˘ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ Î·È Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ ÙˆÓ ÓÂÊÚÒÓˆÓ ·Ú¯›˙ÂÈ Ì ÙËÓ ·Ú·ÁˆÁ‹ ÛËÌ·ÙÔ‰ÔÙÈÎÒÓ ÌÔÚ›ˆÓ ·fi ÙÔ ÂÈı‹ÏÈÔ Ù˘ √∫. ∞˘Ù¿ ‰ÚÔ˘Ó ÛÙÔ ÌÂÛ¤Á¯˘Ì· Î·È ÚÔηÏÔ‡Ó ‰Ú·Ì·ÙÈΤ˜ ·ÏÏ·Á¤˜ ÙfiÛÔ ÛÙË ÌÔÚÊÔÏÔÁ›· ÙˆÓ Î˘ÙÙ¿ÚˆÓ, fiÛÔ Î·È ÛÙËÓ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ, Ì ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· ÙË ÌÂÙ·ÙÚÔ‹ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈ-

ÎÒÓ Î˘ÙÙ¿ÚˆÓ Û ÂÈıËÏȷο. ŒÓ·˜ ·fi ÙÔ˘˜ ÚÒÙÔ˘˜ ÌÂÙ·ÁÚ·ÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, Ô˘ ÂÎÊÚ¿˙ÔÓÙ·È ÛÙÔ ÌÂÛ¤Á¯˘Ì· Û ·fiÎÚÈÛË ÛÙ· Û‹Ì·Ù· ÙÔ˘ ÂÈıËÏ›Ô˘, Â›Ó·È Ô Wilms tumor (WT)-1, Ô ÔÔ›Ô˜ ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ Zn-finger ÚˆÙÂ˚ÓÒÓ. Èڛ˜ ÙËÓ WT-1 ÙÔ ÌÂÛ¤Á¯˘Ì· ·‰˘Ó·Ù› Ó· ‰È·ÊÔÚÔÔÈËı› Û ÓÂÊÚÒÓ˜, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ·ÎÔÏÔ˘ı› ‰È·‰Èηۛ˜ ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓÔ˘ ΢ÙÙ·ÚÈÎÔ‡ ı·Ó¿ÙÔ˘ (36). ™ÙË ıÂÙÈ΋ Ú‡ıÌÈÛË ÙÔ˘ WT-1 Ê·›ÓÂÙ·È Ó· ÂÌϤÎÂÙ·È Ô ·Ú¿ÁÔÓÙ·˜ FGF-2, Ô ÔÔ›Ô˜ ·Ú¿ÁÂÙ·È ·fi Ù· ÂÈıËÏȷο ·ÙÙ·Ú· Ù˘ √∫ (37). ŒÂÈÙ· ·fi ÙËÓ Â·ÁˆÁ‹ ÙÔ˘ WT-1, Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· ·Ú¯›˙Ô˘Ó Ó· ˘ÎÓÒÓÔ˘Ó Î·È Ó· ‰ËÌÈÔ˘ÚÁÔ‡Ó Û˘Ì·Á‹ ÛÊ·ÈÚÈο Û˘Ûۈ̷ÙÒÌ·Ù· Á‡Úˆ ·fi ÙȘ ÎÔÚ˘Ê¤˜ Ù˘ √∫. ∞ÎÔÏÔ˘ı› Ë Î·ıÔÚÈÛÙÈ΋˜ ÛËÌ·Û›·˜ ÁÈ· ÙË ÓÂÊÚÔÁ¤ÓÂÛË ÌÂÙ·ÙÚÔ‹ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Û ÂÈıËÏȷο (mesenchyme-toepithelial transition). ∞fi ÂÈÚ¿Ì·Ù· Û ΢ÙÙ·ÚÔηÏÏȤÚÁÂȘ ‰È·ÈÛÙÒÓÂÙ·È Ô ÛËÌ·ÓÙÈÎfi˜ ÚfiÏÔ˜ ÙˆÓ ÂÎÎÚÈÓfiÌÂÓˆÓ ·Ú·ÁfiÓÙˆÓ FGF-2 Î·È LIF (Leukemia inhibitory factor) ÛÙË ‰È·‰Èηۛ· ·˘Ù‹. ∂ÓÒ Ë FGF-2 ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÙË Û˘Ì‡ÎÓˆÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ, ‰ÂÓ ¤¯ÂÈ ÙËÓ ÈηÓfiÙËÙ· Ó· Ù· ÌÂÙ·ÙÚ¤„ÂÈ Û ÂÈıËÏȷο (38). ∞˘Ùfi ÙÔ ÂÈÙ˘Á¯¿ÓÂÈ Ë LIF, ·ÏÏ¿ ¤ÂÈÙ· ·fi ÙË ‰Ú¿ÛË Ù˘ FGF-2 (39). ™ËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ÓÂÊÚÒÓˆÓ Ê·›ÓÂÙ·È Ó· ·›˙ÂÈ ÙÔ ÁÔÓ›‰ÈÔ Pax2, ÂÊfiÛÔÓ Ë ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÛÂ Û˘ÛÙ‹Ì·Ù· in vitro ηÏÏȤÚÁÂÈ·˜ ÓÂÊÚÒÓ ÂÌÔ‰›˙ÂÈ ÙËÓ Û˘Ûۈ̿وÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È ÙËÓ ÌÂÙ·ÙÚÔ‹ ÙÔ˘˜ Û ÂÈıËÏȷο (40). ¶·ÚfiÌÔÈÔ˜ Ê·ÈÓfiÙ˘Ô˜ ÚÔ·ÙÂÈ ·fi ÙËÓ ¤ÏÏÂÈ„Ë ÙÔ˘ ÁÔÓȉ›Ô˘ Wnt-4, ÙÔ ÔÔ›Ô Îˆ‰ÈÎÔÔÈ› ÌÈ· ÂÎÎÚÈÓfiÌÂÓË ÁÏ˘ÎÔÚˆÙ½ÓË, Ë ÔÔ›· ·Ú¿ÁÂÙ·È ·fi Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· ηٿ ÙË ‰È·‰Èηۛ· Ù˘ Û˘Ì‡ÎÓˆÛ‹˜ ÙÔ˘˜ Á‡Úˆ ·fi ÙËÓ ÎÔÚ˘Ê‹ Ù˘ √∫ (41). ∏ Wnt-4 Â¿ÁÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ›‰ÈÔ˘ ÙÔ˘ ÁÔÓȉ›Ô˘ Ù˘. ∞˘Ùfi˜ ÈÛÙ‡ÂÙ·È fiÙÈ Â›Ó·È ¤Ó·˜ Ì˯·ÓÈÛÌfi˜ Ì ÙÔÓ ÔÔ›Ô Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· “ÌÂÙÚÔ‡Ó” ÙËÓ ˘ÎÓfiÙËÙ¿ ÙÔ˘˜ (42). ∞Ó ‰ËÏ·‰‹ Û˘Ì˘Îӈ̤ӷ ·ÙÙ·Ú· ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ ‚ÚÂıÔ‡Ó Û ÂÚÈ‚¿ÏÏÔÓ Ì ¿ÏÏ· ·ÙÙ·Ú· Ù· ÔÔ›· ÂÎÊÚ¿˙Ô˘Ó Wnt-4, ÙfiÙ ·˘Ù¿ ·˘Í¿ÓÔ˘Ó ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ Wnt-4, ÒÛÙ ӷ ‰ËÌÈÔ˘ÚÁ‹ÛÔ˘Ó ¤Ó·Ó ·ÚÎÂÙ¿ ÌÂÁ¿ÏÔ ÏËı˘ÛÌfi Î·È Ó· ‰È·ÊÔÚÔÔÈËıÔ‡Ó Û ÂÈıËÏȷο ·ÙÙ·Ú·. ŒÓ·˜ Ù¤ÙÔÈÔ˜ Ì˯·ÓÈÛÌfi˜ Ú¤ÂÈ Ê˘ÛÈο Ó· ˘fiÎÂÈÙ·È Û ·˘ÛÙËÚfi ¤ÏÂÁ¯Ô, ÒÛÙ ӷ ·ÔÊ¢¯ı› Ë ¶·È‰È·ÙÚÈ΋ 2006;69:255-267

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ÂÚ›ÙˆÛË Ù˘ ÂÈıËÏÈÔÔ›ËÛ˘ fiÏˆÓ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜. ªÈ· Ù¤ÙÔÈ· ·ÚÓËÙÈ΋ ‰Ú¿ÛË Ê·›ÓÂÙ·È Ó· ¤¯ÂÈ Ë ÂÎÎÚÈÓfiÌÂÓË ÚˆÙ½ÓË sFRP-1, Ë ÔÔ›· ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ Wnt ˘Ô‰Ô¯¤ˆÓ Î·È ·ÓÙ·ÁˆÓ›˙ÂÙ·È ÙËÓ ÚfiÛ‰ÂÛË Ù˘ Wnt-4 ÛÙÔÓ ˘Ô‰Ô¯¤· Frizzled (43). ŒÓ·˜ ‰Â‡ÙÂÚÔ˜ ˘Ô‰Ô¯¤·˜ Ù˘ ›‰È·˜ ÔÈÎÔÁ¤ÓÂÈ·˜, Ô sFRP-2, ·Ú¯›˙ÂÈ Ó· ·Ú¿ÁÂÙ·È ·fi Ù· ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· fiÙ·Ó Û ·˘Ù¿ ·Ú¯›˙ÂÈ ÛÙ·‰È·Î¿ Ó· ÂÍ·ÛıÂÓ› Ë ¤ÎÊÚ·ÛË ÙÔ˘ Wnt-4. ªÂ ·˘Ùfi ÙÔÓ ÙÚfiÔ ÂÈÙ˘Á¯¿ÓÂÙ·È Ë ‰¤ÛÌ¢ÛË Ù˘ Wnt-4 ·fi Ù· ›‰È· Ù· ‰È·ÊÔÚÔÔÈË̤ӷ ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú·, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ sFRP-1, Ë ÔÔ›· ËÁ¿˙ÂÈ ·fi ÙÔ ·‰È·ÊÔÚÔÔ›ËÙÔ ÌÂÛ¤Á¯˘Ì·. √ Ì˯·ÓÈÛÌfi˜ ·˘Ùfi˜ ÏÂÈÙÔ˘ÚÁ› Û·Ó ·ÛÊ·ÏÈÛÙÈ΋ ‰ÈÎÏ›‰· ÒÛÙ ӷ ÂÈÙ¢¯ı› Ô Î·ıÔÚÈÛÌfi˜ Ù˘ Ù‡¯Ë˜ ÙˆÓ Û˘Ì˘ÎÓˆÌ¤ÓˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ, ‰ËÏ·‰‹ Ë ÂÈıËÏÈÔÔ›ËÛ‹ ÙÔ˘˜. √ ÌÔÚÊÔÁÂÓÂÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ FGF8 ÂÎÊÚ¿˙ÂÙ·È ÛÙÔÓ ·Ó·Ù˘ÛÛfiÌÂÓÔ ÓÂÊÚfi, ·Ú¯Èο ÛÙÔ ÌÂÙ·ÓÂÊÚÈÎfi ÌÂÛ¤Á¯˘Ì· Î·È ·ÚÁfiÙÂÚ· ÛÙ· Û˘Ì˘Îӈ̤ӷ ÌÂÛÂÁ¯˘Ì·ÙÈο ·ÙÙ·Ú· Î·È ÛÙ· ·Ú¿ÁˆÁ· ÙÔ˘˜, Ù· ÂÈı‹ÏÈ· ÙˆÓ ÓÂÊÚÒÓˆÓ. ∏ ÂÌ‚Ú˘˚΋ ıÓËÛÈÌfiÙËÙ· Ô˘ ·Ú·ÙËÚÂ›Ù·È ÛÙÔ ÛÙ¿‰ÈÔ Ù˘ Á·ÛÙÚȉ›ˆÛ˘ ÛÙ· FGF8-/- ÔÓÙ›ÎÈ· ‰ÂÓ Â¤ÙÚÂ ÙËÓ ÌÂϤÙË ÙÔ˘ ÚfiÏÔ˘ ÙÔ˘ FGF8 ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ (44). øÛÙfiÛÔ, ·˘Ù‹ η٤ÛÙË ÂÊÈÎÙ‹ Ì ÙËÓ ÈÛÙÔÂȉÈ΋ ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ FGF8 Û ÌÂÛÂÁ¯˘Ì·ÙÈÎÔ‡˜ ΢ÙÙ·ÚÈÎÔ‡˜ Ù‡Ô˘˜, Ë ÔÔ›· Ô‰‹ÁËÛ Û ˘ÔÏ·Û›· ÙˆÓ ÓÂÊÚÒÓ ÏfiÁˆ ÚÔ‚ÏËÌ·ÙÈ΋˜ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙÔ˘ ÂÈıËÏ›Ô˘ ÙˆÓ ÓÂÊÚÒÓˆÓ Î·È ÛËÌ·ÓÙÈο ÌÂȈ̤Ó˘ ‰È·ÎÏ¿‰ˆÛ˘ Ù˘ √∫ (45). ∏ ÌÂÙ·ÙÚÔ‹ ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Û ÂÈıËÏȷο Û˘Óԉ‡ÂÙ·È ·fi ÌÈ· ÛÂÈÚ¿ ·ÏÏ·ÁÒÓ ÛÙËÓ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ. ™˘ÁÎÂÎÚÈ̤ӷ, Ù· Û˘Ì˘Îӈ̤ӷ ·ÙÙ·Ú· ·Ú¯›˙Ô˘Ó Ó· ÂÎÊÚ¿˙Ô˘Ó ÁÔÓ›‰È· ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ÂÈıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ, fiˆ˜ ÂÈıËÏÈ·ÎÔ‡ Ù‡Ô˘ ηÓÙÂÚ›Ó˜ Î·È ÚˆÙ½Ó˜-Û˘ÛÙ·ÙÈο ÙˆÓ ÛÙÂÓÔÛ˘Ó‰¤Û̈Ó, ÂÓÒ ·Ú¿ÏÏËÏ· ·ÓÙÈηıÈÛÙÔ‡Ó Ù· ÌfiÚÈ· ‚ÈÌÂÓÙ›Ó˘ ÙÔ˘ ΢ÙÙ·ÚÔÛÎÂÏÂÙÔ‡ ÙÔ˘˜ Ì ΢ÙÔÎÂÚ·Ù›Ó˜ (46-48). ∆¤ÏÔ˜, fiˆ˜ Û fiϘ ÙȘ ÂÈıËÏȷΤ˜ ‰Ô̤˜ ·Ú·ÙËÚÂ›Ù·È Ë ‰ËÌÈÔ˘ÚÁ›· ÌÈ·˜ ηÓÔÓÈ΋˜ ‚·ÛÈ΋˜ ÌÂÌ‚Ú¿Ó˘ (49,50).

øڛ̷ÓÛË ÙˆÓ ÓÂÊÚÒÓˆÓ √ ηıÔÚÈÛÌfi˜ ÙˆÓ ‰È·ÊfiÚˆÓ ÙÌËÌ¿ÙˆÓ ÙˆÓ ÓÂÊÚÒÓˆÓ ·Ú¯›˙ÂÈ ÌÂÙ¿ ÙËÓ ÂÈıËÏÈÔÔ›ËÛË ÙˆÓ Û˘Ì˘ÎÓˆÌ¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ÌÂÛÂÁ¯‡¶·È‰È·ÙÚÈ΋ 2006;69:255-267

Ì·ÙÔ˜. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ˆÚ›Ì·ÓÛ˘, Ù· ·Ú¯Èο ÛÊ·ÈÚÈο ÂÈı‹ÏÈ· ÙˆÓ ÓÂÊÚÒÓˆÓ ÌÂÙ·‚¿ÏÏÔÓÙ·È Û ÛÈÁÌÔÂȉ‹ ÛˆÏËÓ¿ÚÈ·. ™ÙÔ ¿ÎÚÔ ÙˆÓ ÛˆÏËÓ·Ú›ˆÓ, fiÔ˘ ı· ‰ËÌÈÔ˘ÚÁËıÔ‡Ó ·ÚÁfiÙÂÚ· Ù· ÓÂÊÚÈο ÛÂÈÚ¿Ì·Ù·, ˘¿Ú¯ÂÈ ·˘ÍË̤ÓË ÂÓÂÚÁfiÙËÙ· ÙÔ˘ ·Ú¿ÁÔÓÙ· WT-1. H ¤ÎÊÚ·ÛË ÙÔ˘ WT-1 ÛÙËÓ ÂÚÈÔ¯‹ ·˘Ù‹ ηٷÛÙ¤ÏÏÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ Pax2. ∞˘Ùfi Ê·›ÓÂÙ·È Ó· ·ÔÙÂÏ› ¤Ó·Ó Ôχ ÛËÌ·ÓÙÈÎfi Ú˘ıÌÈÛÙÈÎfi Ì˯·ÓÈÛÌfi, ηıÒ˜ Û ÂÈÚ¿Ì·Ù· ¤ÎÙÔ˘ ¤ÎÊÚ·Û˘ ÙÔ˘ Pax-2 Û fiÏÔ ÙÔ ÙÌ‹Ì· ÙÔ˘ ÂÈıËÏ›Ô˘ ÙˆÓ ÓÂÊÚÒÓˆÓ ÂÌÔ‰›˙ÂÙ·È Ë ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ÓÂÊÚÈÎÒÓ ÛÂÈÚ·Ì¿ÙˆÓ (51). ∞ÍÈÔÛËÌ›ˆÙË Â›Ó·È Ë Û˘ÌÌÂÙÔ¯‹ ÙˆÓ ·Ú·ÁfiÓÙˆÓ Pax-2 Î·È WT-1 Û ÔÏÏ·Ï¿ ÛÙ¿‰È· Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ ÓÂÊÚÒÓ. ª¿ÏÈÛÙ·, ·ÎfiÌ· Î·È ÔÈ ‰È·ÊÔÚÂÙÈΤ˜ ÈÛÔÌÔÚʤ˜ Ù˘ WT-1 ¤¯Ô˘Ó Û˘Û¯ÂÙÈÛı› ̠ͯˆÚÈÛÙ¤˜ ÏÂÈÙÔ˘ÚÁ›Â˜ ÛÙËÓ ˆÚ›Ì·ÓÛË ÙˆÓ ÌÂÙ¿ÓÂÊÚˆÓ. ™˘ÁÎÂÎÚÈ̤ӷ, Û ÁÂÓÂÙÈο ÙÚÔÔÔÈË̤ӷ ÔÓÙ›ÎÈ· Ô˘ ÂÎÊÚ¿˙Ô˘Ó ÌfiÓÔ ÙËÓ ÈÛÔÌÔÚÊ‹ -KTS ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È ÓÂÊÚÈο ÛÂÈÚ¿Ì·Ù· ÛÙ· ÔÔ›· Ù· Ô‰Ô·ÙÙ·Ú· ‰ÂÓ Û¯ËÌ·Ù›˙Ô˘Ó ÙÔ˘˜ Ù˘ÈÎÔ‡˜ Ô‰›ÛÎÔ˘˜, ÂÓÒ Ë ·ÔÎÏÂÈÛÙÈ΋ ¤ÎÊÚ·ÛË Ù˘ +KTS ÈÛÔÌÔÚÊ‹˜ Ô‰ËÁ› ÛÙËÓ ‰ËÌÈÔ˘ÚÁ›· ÂÏ¿¯ÈÛÙˆÓ Î·È ·ÓÒÚÈÌˆÓ ÓÂÊÚÈÎÒÓ ÛÂÈÚ·Ì¿ÙˆÓ (52). √ ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Brn-1 ÂÎÊÚ¿˙ÂÙ·È Î˘Ú›ˆ˜ ÛÙÔ Ó¢ÚÈÎfi Û‡ÛÙËÌ· Î·È Ë ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÚÔηÏ› ‹Ș ·ÏÏÔÈÒÛÂȘ Û ‰Ô̤˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘, ÁÂÁÔÓfi˜ Ô˘ ‰ÂÓ ‰ÈηÈÔÏÔÁ› ÙÔ ı¿Ó·ÙÔ ÙˆÓ ÌÂÙ·ÏÏ·ÁÌ¤ÓˆÓ ÔÓÙÈÎÒÓ Ì¤Û· ÛÙȘ ÚÒÙ˜ 48 ÒÚ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË. ∞fi ÙËÓ ÚfiÛÊ·ÙË ÏÂÙÔÌÂÚ‹ ÂͤٷÛË ÙˆÓ ÓÂÊÚÒÓ ÙˆÓ Brn-1-/- ÔÓÙÈÎÒÓ ÚԤ΢„Â Ô ÛËÌ·ÓÙÈÎfi˜ ÚfiÏÔ˜ ÙÔ˘ ÂÓ ÏfiÁˆ ÁÔÓȉ›Ô˘ ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ¿ˆ ÛˆÏËÓ·Ú›ˆÓ ÙˆÓ ÓÂÊÚÒÓˆÓ. ™˘ÁÎÂÎÚÈ̤ӷ, ·Ú·ÙËÚÂ›Ù·È fiÙÈ Ë ÂÈÌ‹Î˘ÓÛË Ù˘ ·Á·Ï˘ ÙÔ˘ Henle ‰ÂÓ ÂÂÎÙ›ÓÂÙ·È ÚÔ˜ Ù· ÂÛÒÙÂÚ· ÙÌ‹Ì·Ù· ÙÔ˘ ÓÂÊÚÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ (medulla), ·ÏÏ¿ ÛÙ·Ì·Ù¿ ÚfiˆÚ· (53). ÕÏÏÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ˆÚ›Ì·ÓÛË ÙˆÓ ÓÂÊÚÒÓˆÓ Â›Ó·È Ô Lmx-1b, Ë ·Ô˘Û›· ÙÔ˘ ÔÔ›Ô˘ ÚÔηÏ› ‰È·Ù·Ú·¯¤˜ ÛÙÔ Ê˘ÛÈÔÏÔÁÈÎfi Û¯ËÌ·ÙÈÛÌfi Ù˘ ‚·ÛÈ΋˜ ÌÂÌ‚Ú¿Ó˘ ÙˆÓ ÛÂÈÚ·Ì¿ÙˆÓ (54), ÙÔ ÌÂÌ‚Ú·ÓÈÎfi ÛËÌ·ÙÔ‰ÔÙÈÎfi ÌfiÚÈÔ Notch-2 (55) ηıÒ˜ Î·È Ô ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Lim1 (8). ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ·ÔÎ¿Ï˘„·Ó ÙÔÓ ÚfiÏÔ ÙˆÓ ÚÂÛÂÓÈÏÈÓÒÓ ÛÙËÓ ‰È·ÊÔÚÔÔ›ËÛË ÙÔ˘ ÂÈıËÏ›Ô˘ ÙˆÓ ÓÂÊÚÒÓˆÓ. √È ÚÂÛÂÓÈϛӘ Â›Ó·È ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ ÚˆÙ½Ó˜, ÔÈ Ôԛ˜ Â›Ó·È ÁÓˆÛÙ¤˜ ÁÈ· ÙÔÓ ÚfiÏÔ ÙÔ˘˜ ÛÙËÓ ÚˆÙÂfiÏ˘ÛË

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°ÔÓ›‰È· ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ

ÙÔ˘ ‚-·Ì˘ÏÔÂȉԇ˜ Î·È ÙÔ˘ ÛËÌ·ÙÔ‰ÔÙÈÎÔ‡ ÌÔÚ›Ô˘ Notch, ÂÓÒ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙȘ ÚÂÛÂÓÈϛӘ Psn-1 Î·È Psn-2 ¢ı‡ÓÔÓÙ·È ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÓfiÛÔ˘ ÙÔ˘ Alzheimer (56). ∏ Psn-1 Î·È Psn-2 ¤¯Ô˘Ó Û˘ÌÏËڈ̷ÙÈΤ˜ ÏÂÈÙÔ˘ÚÁ›Â˜, ÂÓÒ ‰ÈÏ¿ ÔÌfi˙˘Á· ÔÓÙ›ÎÈ· (Psn-1/2-/-) Âı·›ÓÔ˘Ó ÚÈÓ ÙË ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ÓÂÊÚÒÓ ·fi ÚÔ‚Ï‹Ì·Ù· ‰È·ÊÔÚÔÔ›ËÛ˘ ÛÙÔ˘˜ ۈ̛Ù˜ (57). ∏ ¯Ú‹ÛË ÂÓfi˜ ‰È·ÁÔÓȉ›Ô˘ ÙÔ ÔÔ›Ô ÂÎÊÚ¿˙ÂÈ ÙÔ Psn-1 ÛÙȘ ÂËÚ·˙fiÌÂÓ˜ ·fi ÙÔÓ Ê·ÈÓfiÙ˘Ô ÂÚÈÔ¯¤˜ Â¤ÙÚ„ ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ Psn-1/2-/- ˙ÒˆÓ Ì¤¯ÚÈ ÙË Á¤ÓÓËÛË Î·È ÙËÓ ·Ó¿Ï˘ÛË ÙÔ˘ Ê·ÈÓÔÙ‡Ô˘ ÛÙ· ÓÂÊÚ¿. ∞ԉ›¯ÙËΠfiÙÈ Ë ÓÂÊÚÔÁ¤ÓÂÛË ‰ÈÂÍ¿ÁÂÙ·È Ê˘ÛÈÔÏÔÁÈο ̤¯ÚÈ Î·È ÚÈÓ ÙÔ ÛÙ¿‰ÈÔ Ù˘ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙÔ˘ ÂÈıËÏ›Ô˘ ÙˆÓ ÓÂÊÚÒÓˆÓ Û ÛÈÁÌÔÂȉ‹ ÛˆÏËÓ¿ÚÈ·, Ù· ÔÔ›· ‰ÂÓ ·ÓȯÓ‡ÔÓÙ·È ÛÙ· ‰ÈÏ¿ ÌÂÙ·ÏÏ·Á̤ӷ ˙Ò· (58). ∏ ·ÚÔ˘Û›· ÛˆÏËÓ·Ú›ˆÓ Û˘Ó‰Â‰ÂÌ¤ÓˆÓ Ì ٷ ·ıÚÔÈÛÙÈο ÛˆÏËÓ¿ÚÈ· ·ÏÏ¿ Ë ÌË ‰ËÌÈÔ˘ÚÁ›· ÂÁÁ‡˜ ÛˆÏËÓ·Ú›ˆÓ ·ÔηχÙÂÈ ÙÔÓ ÚfiÏÔ ÙˆÓ ÚÂÛÂÓÈÏÈÓÒÓ ÛÙË ÌÔÚÊÔÔ›ËÛË (patterning) ÙÔ˘ ÂÈıËÏÈÔÔÈË̤ÓÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜. ¶Ôχ Ï›Á· Â›Ó·È Ì¤¯ÚÈ Û‹ÌÂÚ· ÁÓˆÛÙ¿ Û¯ÂÙÈο Ì ÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ˘fiÏÔÈˆÓ ÙÌËÌ¿ÙˆÓ ÙˆÓ ÓÂÊÚÒÓˆÓ. ∏ ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ÌÂÙ·ÁÚ·ÊÈÎÔ‡ ·Ú¿ÁÔÓÙ· HNF-1, Ô ÔÔ›Ô˜ ÂÎÊÚ¿˙ÂÙ·È Û fiÏ· Ù· ÙÌ‹Ì·Ù· ÙˆÓ ÓÂÊÚÒÓˆÓ, ÂÎÙfi˜ ·fi Ù· ÛÂÈÚ¿Ì·Ù·, ·ÔÎ¿Ï˘„ ÙÔÓ ÚfiÏÔ Ù˘ ·Ú·¿Óˆ ÚˆÙ½Ó˘ ÛÙË Ê˘ÛÈÔÏÔÁÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÂÁÁ‡˜ ÛˆÏËÓ·Ú›ˆÓ. ™˘ÁÎÂÎÚÈ̤ӷ, Ë ¤ÏÏÂÈ„Ë Ù˘ HNF-1 ÚÔηÏ› ‰Ú·ÛÙÈ΋ Ì›ˆÛË Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ ÁÔÓȉ›Ô˘ SGLT (Sodium glucose transporter)-2, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÚÔηÏÂ›Ù·È ÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ Fanconi Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÁÏ˘ÎÔ˙Ô˘Ú›· Î·È ·ÌÈÓÔÍÔ˘Ú›· (59).

∏ Û˘Ì‚ÔÏ‹ ÙÔ˘ ÛÙÚÒÌ·ÙÔ˜ ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÓÂÊÚÈÎÒÓ Î˘ÙÙ·ÚÈÎÒÓ Ù‡ˆÓ ∆Ô ÓÂÊÚÈÎfi ÛÙÚÒÌ· ÚÔ·ÙÂÈ ·fi ÙÔ ÌÂÛ¤Á¯˘Ì·, ÙÔ ÔÔ›Ô ‰ÂÓ ÂÈıËÏÈÔÔÈÂ›Ù·È Î·Ù¿ ÙË ‰È·‰Èηۛ· ÙÔ˘ Û¯ËÌ·ÙÈÛÌÔ‡ ÙˆÓ ÓÂÊÚÒÓˆÓ. ¶·ÚfiÏÔ Ô˘ ·Ú¯Èο ›¯Â ÚÔÙ·ı› ¤Ó·˜ ηı·Ú¿ ˘ÔÛÙËÚÈÎÙÈÎfi˜ ÚfiÏÔ˜ ÙÔ˘ ÛÙÚÒÌ·ÙÔ˜ ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ, ÂÓÙÔ‡ÙÔȘ, Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ·ÔηχÊıËÎÂ Ë ÛËÌ·ÓÙÈ΋ Û˘Ì‚ÔÏ‹ ÙÔ˘ ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÓÂÊÚÈÎÒÓ Î˘ÙÙ·ÚÈÎÒÓ Ù‡ˆÓ. √ ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Foxd1, Ô˘ ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ

ÚˆÙÂ˚ÓÒÓ Forkhead, ÂÎÊÚ¿˙ÂÙ·È ¤ÓÙÔÓ· ÛÙÔ ÛÙÚÒÌ· ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÊÏÔÈÔ‡. ∏ ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Foxd1 ÚÔηÏ› ÌÈ· ÛÂÈÚ¿ ·fi ÚÔ‚Ï‹Ì·Ù· ÛÙÔ˘˜ ÓÂÊÚÔ‡˜, fiˆ˜ ÂÏϷو̷ÙÈ΋ ‰È·ÎÏ¿‰ˆÛË Ù˘ √∫ Î·È ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÓÂÊÚÒÓˆÓ. ∂ÈϤÔÓ, ÔÈ ÓÂÊÚÔ› ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Û˘Á¯ˆÓÂ˘Ì¤ÓÔÈ Î·È ÂÓÙÔ›˙ÔÓÙ·È ¤ÎÙÔ· ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ˘¤ÏÔ˘ (60). ∏ ·ÈÙ›· ÁÈ· ÙË ÌË Ê˘ÛÈÔÏÔÁÈ΋ ı¤ÛË Î·È ÙË Û˘Á¯ÒÓ¢ÛË ÙˆÓ ÓÂÊÚÒÓ ÛÙ· Foxd1-/- ÔÓÙ›ÎÈ· ·ԉ›¯ÙËΠfiÙÈ Â›Ó·È Ë ÂÏÏÈ‹˜ ‰È·ÊÔÚÔÔ›ËÛË Î˘ÙÙ·ÚÈÎÒÓ Ù‡ˆÓ Ù˘ ÓÂÊÚÈ΋˜ ο„·˜ (61). ∆Ô ÁÂÁÔÓfi˜ fiÙÈ Ë ·ÓÂ¿ÚÎÂÈ· ÁÔÓȉ›ˆÓ fiˆ˜ ÙÔ Foxd1 Ô˘ ÂÎÊÚ¿˙ÂÙ·È ÛÙÔ ÛÙÚÒÌ· ÚÔηÏ› ÚÔ‚Ï‹Ì·Ù· ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙÔ˘ ÂÈıËÏ›Ô˘ ÙˆÓ ÓÂÊÚÒÓˆÓ, ·ÔηχÙÂÈ ÙËÓ ‡·ÚÍË ÛËÌ·ÙÔ‰fiÙËÛ˘ ÌÂٷ͇ ÙÔ˘ ÛÙÚÒÌ·ÙÔ˜ Î·È ÙÔ˘ ÂÈıËÏÈÔÔÈË̤ÓÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ / √∫. ∞˘Ùfi ÚÔ·ÙÂÈ Â›Û˘ ·fi ÂÈÚ¿Ì·Ù· ÛÙ· ÔÔ›· ÂÓ¤¯ÂÙ·È Ô ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Pod1. ∆Ô ÁÔÓ›‰ÈÔ Pod1 ÂÎÊÚ¿˙ÂÙ·È ÛÙÔ ÌÂÛ¤Á¯˘Ì· Û ·ÙÙ·Ú· ·fi Ù· ÔÔ›· ı· ÚÔ·„Ô˘Ó Î˘ÙÙ·ÚÈÎÔ› Ù‡ÔÈ ÙÔ˘ ÛÙÚÒÌ·ÙÔ˜ ·ÏÏ¿ Î·È Û ·˘Ù¿ Ù· ÔÔ›· ı· ‰È·ÊÔÚÔÔÈËıÔ‡Ó ÛÙÔ˘˜ ÓÂÊÚÒÓ˜. ™Ù· ‰È·ÊÔÚÔÔÈË̤ӷ ÓÂÊÚÈο ÛÂÈÚ¿Ì·Ù· ÙÔ Pod1 ÂÎÊÚ¿˙ÂÙ·È ÂȉÈο ÛÙ· Ô‰Ô·ÙÙ·Ú· (62). ™Â Pod1-/- ÔÓÙ›ÎÈ· ÚÔηÏÂ›Ù·È ÌÂȈ̤ÓË ‰È·ÎÏ¿‰ˆÛË Ù˘ √∫, ηı˘ÛÙÂÚË̤ÓË ÂÈıËÏÈÔÔ›ËÛË ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜, ÂÓÒ Ù· Ô‰Ô·ÙÙ·Ú· ‰ÂÓ ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È. ∂ÈϤÔÓ, ‰ÂÓ ·ÓȯÓ‡ÔÓÙ·È Ï‹Úˆ˜ ‰È·ÊÔÚÔÔÈË̤ӷ ÓÂÊÚÈο ÛÂÈÚ¿Ì·Ù·, ÂÓÒ ·˘Ù¿ Ô˘ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È Â›Ó·È ÌÂȈ̤ӷ Û ·ÚÈıÌfi (63). ∏ ¯Ú‹ÛË ÔÌfi˙˘ÁˆÓ ÂÌ‚Ú˘˚ÎÒÓ ‚Ï·ÛÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÁÈ· ÙËÓ Î·Ù·Û΢‹ ¯ÈÌ·ÈÚÈÎÒÓ ÔÓÙÈÎÒÓ ·¤‰ÂÈÍ fiÙÈ Ë ·ÚÔ˘Û›· Ù˘ Pod1 ÛÙÔ ÛÙÚÒÌ· ·ÔηıÈÛÙ¿ ÙÔÓ ¿ÁÚÈÔ˘ Ù‡Ô˘ Ê·ÈÓfiÙ˘Ô ÛÙ· ÓÂÊÚÈο ÛÂÈÚ¿Ì·Ù·, οÙÈ ÙÔ ÔÔ›Ô Û˘ÓËÁÔÚ› ˘¤Ú Ù˘ ‡·Ú͢ ÛËÌÔÙÔ‰ÔÙÈÎÒÓ ÌÔÓÔ·ÙÈÒÓ, Ù· ÔÔ›· ËÁ¿˙Ô˘Ó ·fi ÙÔ ÓÂÊÚÈÎfi ÛÙÚÒÌ· (64).

√ ÚfiÏÔ˜ ÂÍˆÎ˘ÙÙ¿ÚÈˆÓ ÚˆÙÂ˚ÓÒÓ ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ ∂ÎÙfi˜ ·fi Ù· ÛËÌ·ÙÔ‰ÔÙÈο ÌfiÚÈ· Î·È ÙÔ˘˜ ÌÂÙ·ÁÚ·ÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, ÛËÌ·ÓÙÈ΋ Â›Ó·È Ë Û˘Ì‚ÔÏ‹ ÔÚÈÛÌ¤ÓˆÓ Û˘ÛÙ·ÙÈÎÒÓ Ù˘ ÂÍˆÎ˘ÙÙ¿ÚÈ·˜ ‡Ï˘ ÛÙËÓ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ. ∞·Ú·›ÙËÙÔ˜ ·ԉ›¯ÙËÎÂ Ô ÚfiÏÔ˜ Ù˘ ıÂÈÈ΋˜ Ë·Ú¿Ó˘, Û˘ÛÙ·ÙÈÎÔ‡ ÙˆÓ Ï·Á›ˆÓ ·Ï˘Û›‰ˆÓ ÙˆÓ ÚˆÙÂÔÁÏ˘Î·ÓÒÓ. ∏ ¤ÏÏÂÈ„Ë ÙÔ˘ ÂÓ˙‡ÌÔ˘ heparan sulfate 2-sulfotransferase (HS2ST) ¶·È‰È·ÙÚÈ΋ 2006;69:255-267

264

¶.¶. ¶¤ÙÚÔ˘

ÚÔηÏ› ÓÂÊÚÈ΋ ·ÁÂÓÂÛ›·, Ô˘ ÔÊ›ÏÂÙ·È Û ÚÔ‚ÏËÌ·ÙÈ΋ Û˘Ì‡ÎÓˆÛË ÙˆÓ ÌÂÛÂÁ¯˘Ì·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È ‰È·ÎÏ¿‰ˆÛË Ù˘ √∫, ÂÓÒ Ù· ·Ú¯Èο ÛÙ¿‰È· Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ ÙÔ˘ ÌÂÙ¿ÓÂÊÚÔ˘, ‰ËÏ·‰‹ Ô Î·ıÔÚÈÛÌfi˜ ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ Î·È Ë Â·ÁˆÁ‹ Ù˘ √∫ ‰ÈÂÍ¿ÁÔÓÙ·È Î·ÓÔÓÈο (65). ™Ô‚·ÚfiÙÂÚÔ˜ Â›Ó·È Ô Ê·ÈÓfiÙ˘Ô˜ Ô˘ ÚÔ·ÙÂÈ ·fi ÙËÓ ÛÙÔ¯Â˘Ì¤ÓË ·ÂÓÂÚÁÔÔ›ËÛË Ù˘ ÂÚÈÔ¯‹˜ ·ÏÏËÏÂ›‰Ú·Û˘ Ù˘ Ï·ÌÈÓ›Ó˘-Á1 Ì ÙÔ ÓȉÔÁfiÓÔ-1. ∏ ·Ô˘Û›· ·ÏÏËÏÂ›‰Ú·Û˘ ÌÂٷ͇ Ï·ÌÈÓ›Ó˘-Á1 Î·È ÓȉÔÁfiÓÔ˘-1 ÚÔηÏ› ‰È·Ù·Ú·¯¤˜ ÛÙËÓ Û˘ÁÎÚfiÙËÛË ÙˆÓ ‚·ÛÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ Î·È Ô‰ËÁ› ¤Ó· ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ÙˆÓ ·Ú·¿Óˆ ÌÂÙ·ÏÏ·ÁÌ¤ÓˆÓ ˙ÒˆÓ Û ÓÂÊÚÈ΋ ·ÁÂÓÂÛ›· Ô˘ ÔÊ›ÏÂÙ·È ÛÙËÓ ÚÔ‚ÏËÌ·ÙÈ΋ ÂÈÌ‹Î˘ÓÛË ÙÔ˘ ÌÂÛÔÓÂÊÚÈÎÔ‡ fiÚÔ˘ ÚÈÓ ÙË ‰ËÌÈÔ˘ÚÁ›· Ù˘ √∫ (66). ¢È·Ù·Ú·¯¤˜ ÛÙËÓ Â·ÁˆÁ‹ Î·È ÙË ‰È·ÎÏ¿‰ˆÛË Ù˘ √∫ ÚÔηÏÔ‡ÓÙ·È ·fi ÙËÓ ¤ÏÏÂÈ„Ë Ù˘ ÈÓÙÂÁÎÚ›Ó˘-·8 (67). √È ÈÓÙÂÁÎÚ›Ó˜ Â›Ó·È ‰È·ÌÂÌ‚Ú·ÓÈΤ˜ ÚˆÙ½Ó˜ ÔÈ Ôԛ˜ Û˘Ó‰¤Ô˘Ó ÙË ‚·ÛÈ΋ ÌÂÌ‚Ú¿ÓË Ì ٷ ÂÈıËÏȷο ·ÙÙ·Ú·. ∂Ô̤ӈ˜, fiˆ˜ ÚÔ·ÙÂÈ ·fi Ù· ·Ú·¿Óˆ, Ë ·ÎÂÚ·ÈfiÙËÙ· ÙˆÓ ‚·ÛÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ ÙˆÓ ÓÂÊÚÈÎÒÓ ÂÈıËÏ›ˆÓ Â›Ó·È ··Ú·›ÙËÙË ÚÔ¸fiıÂÛË ÁÈ· ÙËÓ ÔÌ·Ï‹ ·Ó¿Ù˘ÍË ÙˆÓ ÓÂÊÚÒÓ. ¶ÚfiÛÊ·Ù· Ù·˘ÙÔÔÈ‹ıËΠÙÔ ÁÔÓ›‰ÈÔ Fras1 ÙÔ ÔÔ›Ô Îˆ‰ÈÎÔÔÈ› ÌÈ· Ó¤· ÂÍˆÎ˘ÙÙ¿ÚÈ· ÚˆÙ½ÓË, Ë ÔÔ›· ÂÓÙÔ›˙ÂÙ·È Û ÂÈıËÏȷΤ˜ ‚·ÛÈΤ˜ ÌÂÌ‚Ú¿Ó˜ ηٿ ÙËÓ ÂÌ‚Ú˘ÔÁ¤ÓÂÛË (68-70). ™ÙÔ˘˜ ·Ó·Ù˘ÛÛÔ̤ÓÔ˘˜ ÓÂÊÚÔ‡˜ Ë Fras1 ÂÓÙÔ›˙ÂÙ·È ÛÙË ‚·ÛÈ΋ ÌÂÌ‚Ú¿ÓË Ù˘ √∫ Î·È ÙˆÓ ÓÂÊÚÒÓˆÓ. ªÂÙ·ÏÏ¿ÍÂȘ ÛÙo ÁÔÓ›‰ÈÔ Fras1 ÚÔηÏÔ‡Ó ÙÔ Û‡Ó‰ÚÔÌÔ Fraser ÛÙÔÓ ¿ÓıÚˆÔ, ¤Ó· ·fi Ù· ΢ڛ· ‰È·ÁÓˆÛÙÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ÔÔ›Ô˘ Â›Ó·È Ë ·ÁÂÓÂÛ›· ÙˆÓ ÓÂÊÚÒÓ. ¶·ÚfiÌÔÈÔ˜ Ê·ÈÓfiÙ˘Ô˜ ÚԤ΢„ ·fi ÙËÓ ÛÙÔ¯Â˘Ì¤ÓË ·ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Fras1 ÛÙÔÓ ÔÓÙÈÎfi (68). ªÂٷ͇ ¿ÏÏˆÓ Ê·ÈÓÔÙ˘ÈÎÒÓ ·ÏÏÔÈÒÛÂˆÓ ÂΉËÏÒÓÂÙ·È Û ¤Ó· ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi ÙˆÓ ÌÂÙ·ÏÏ·ÁÌ¤ÓˆÓ ˙ÒˆÓ ·ÁÂÓÂÛ›· ÙÔ˘ ÂÓfi˜ ‹ Î·È ÙˆÓ ‰‡Ô ÓÂÊÚÒÓ. ∞˘Ù‹ ÔÊ›ÏÂÙ·È ÛÙËÓ ·‰˘Ó·Ì›· ÙÔ˘ ÌÂÛÂÁ¯‡Ì·ÙÔ˜ Ó· ÂÈıËÏÈÔÔÈËı›, Ì ·ÔÙ¤ÏÂÛÌ· Û ·˘Ùfi Ó· ÂÓÂÚÁÔÔÈÔ‡ÓÙ·È ‰È·‰Èηۛ˜ ·fiÙˆÛ˘, ÂÓÒ Ë Â·ÁˆÁ‹ Ù˘ √∫ Î·È Ë ÂÈÛ‚ÔÏ‹ Ù˘ ÛÙÔ ÌÂÛ¤Á¯˘Ì· Ê·›ÓÂÙ·È Ó· ‰ÈÂÍ¿ÁÔÓÙ·È Î·ÓÔÓÈο. √È ›‰È˜ ·Èٛ˜ Ô‰ËÁÔ‡Ó Û ·ÁÂÓÂÛ›· ÙˆÓ ÓÂÊÚÒÓ ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ¤ÏÏÂȄ˘ Ù˘ ÚˆÙ½Ó˘ Grip1 (71). H Grip1, Ë ÔÔ›· Â›Ó·È Î˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈ΋ Î·È ·Ó‹ÎÂÈ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ÙˆÓ PDZ ÚˆÙÂ˚ÓÒÓ ·ÏÏËÏÂȉڿ Ì ÙËÓ Fras1 Î·È Î·Ù¢ı‡ÓÂÈ ÙË ÌÂÙ·ÊÔÚ¿ Î·È ÙËÓ ¤ÍÔ‰Ô Ù˘ ¶·È‰È·ÙÚÈ΋ 2006;69:255-267

·fi ÙËÓ Ôψ̤ÓË ÏÂ˘Ú¿ ÙˆÓ ÂÈıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ. ∏ Fras1 ·ÔÙÂÏ› Â›Û˘, ÙÔ È‰Ú˘ÙÈÎfi ̤ÏÔ˜ ÌÈ·˜ ηÈÓÔ‡ÚÁÈ·˜ ÔÈÎÔÁ¤ÓÂÈ·˜ ‰ÔÌÈο Û˘ÁÁÂÓÈÎÒÓ ÂÍˆÎ˘ÙÙ¿ÚÈˆÓ ÚˆÙÂ˚ÓÒÓ. ∂ӉȷʤÚÔÓ ·ÔÙÂÏ› ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÔÈ ÚˆÙ½Ó˜ ·˘Ù¤˜, Fras1 related extracellular matrix (Frem)-1 Î·È Frem-2 ÂÌϤÎÔÓÙ·È Î·È ÏÂÈÙÔ˘ÚÁÈο ÛÙȘ ›‰È˜ ‰È·‰Èηۛ˜, ·ÊÔ‡ Ë ·ÓÂ¿ÚÎÂÈ· ÙÔ˘˜ ÚÔηÏ› ·ÚfiÌÔÈÔ ÂÌ‚Ú˘˚Îfi Ê·ÈÓfiÙ˘Ô. ∫·È ÛÙȘ ‰‡Ô ÂÚÈÙÒÛÂȘ ÚÔ·ÙÂÈ ·ÁÂÓÂÛ›· ÙˆÓ ÓÂÊÚÒÓ ÌÂÙ¿ ÙËÓ Â·ÁˆÁ‹ Ù˘ √∫ (72,73). ∞ÍÈÔÛËÌ›ˆÙÔ Â›Ó·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÙÌ‹Ì·Ù· ÙˆÓ ÚˆÙÂ˚ÓÒÓ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜ Fras ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÌÔÈfiÙËÙ· Ì ÂÚÈÔ¯¤˜ ÔÈ Ôԛ˜ ·ÏÏËÏÂȉÚÔ‡Ó Ì ·˘ÍËÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜. ∂Ô̤ӈ˜, ÔÈ ÚˆÙ½Ó˜ Fras1 Î·È Frem1/2 Èı·ÓfiÓ Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó ˆ˜ ‰ÔÌÈο ÛÙÔȯ›· ÛÙË Û˘ÁÎÚfiÙËÛË ÙˆÓ ‚·ÛÈÎÒÓ ÌÂÌ‚Ú·ÓÒÓ, ·ÏÏ¿ Î·È ˆ˜ Ú˘ıÌÈÛÙ¤˜ ÛËÌ·ÙÔ‰ÔÙ‹ÛÂˆÓ ÌÂٷ͇ ÂÈıËÏ›Ô˘ Î·È ÌÂÛÂÁ¯‡Ì·ÙÔ˜.

™˘ÌÂÚ·ÛÌ·ÙÈο Û¯fiÏÈ· ∏ ‰È·‰Èηۛ· Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ ÓÂÊÚÒÓ ÂÍ·ÚÙ¿Ù·È Û ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ·fi ÙËÓ ·ÌÊ›‰ÚÔÌË ÛËÌ·ÙÔ‰fiÙËÛË ÌÂٷ͇ ÂÈıËÏ›Ô˘ Î·È ÌÂÛÂÁ¯‡Ì·ÙÔ˜, Ë ÔÔ›· ˘fiÎÂÈÙ·È Û ·˘ÛÙËÚfi Ú˘ıÌÈÛÙÈÎfi ¤ÏÂÁ¯Ô. √È Ê·ÈÓÔÙ˘ÈΤ˜ ·ÏÏÔÈÒÛÂȘ Ô˘ ÚÔ·ÙÔ˘Ó ·fi ÙË ÛÙÔ¯Â˘Ì¤ÓË ·ÂÓÂÚÁÔÔ›ËÛË ÁÔÓȉ›ˆÓ ÛÙÔÓ ÔÓÙÈÎfi ¤¯Ô˘Ó ÂÓÈÛ¯‡ÛÂÈ ÛËÌ·ÓÙÈο ÙË ÁÓÒÛË ÁÈ· ÙÔÓ ÚfiÏÔ Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÌÔÚ›ˆÓ ÛÙË ÓÂÊÚÔÁ¤ÓÂÛË. ¶·ÚfiÏ· ·˘Ù¿, ¤Ó· ÌÂÁ¿ÏÔ Úfi‚ÏËÌ· Ô˘ ÚÔ·ÙÂÈ Ì ٤ÙÔÈÔ˘ ›‰Ô˘˜ ÚÔÛÂÁÁ›ÛÂȘ Â›Ó·È fiÙÈ Û ·ÚÎÂÙ¤˜ ÂÚÈÙÒÛÂȘ ÚÔηÏÂ›Ù·È ÂÌ‚Ú˘˚΋ ıÓËÛÈÌfiÙËÙ· ‹ ‰È·Ù·Ú·¯¤˜ ÛÙ· ÚÒÈÌ· ÛÙ¿‰È· Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ ÙˆÓ ÓÂÊÚÒÓ Ô˘ ‰ÂÓ ÂÈÙÚ¤Ô˘Ó ÙË ÌÂϤÙË Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ ÌÔÚ›ˆÓ ÛÙȘ ÌÂÙ¤ÂÈÙ· Ê¿ÛÂȘ Ù˘ ·Ó¿Ù˘Í˘. ∂Ô̤ӈ˜, ÈÔ Û‡ÓıÂÙ˜ ÚÔÛÂÁÁ›ÛÂȘ fiˆ˜ Ë ÈÛÙÔÂȉÈ΋ ‹ Ë Â·ÁÔ̤ÓË ·ÂÓÂÚÁÔÔ›ËÛË ÁÔÓȉ›ˆÓ Â›Ó·È ··Ú·›ÙËÙ˜ ÁÈ· ÙËÓ ·ÔÎ¿Ï˘„Ë ÙÔ˘ ÚfiÏÔ˘ Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ·Ú·ÁfiÓÙˆÓ ÛÙ· ‰È·ÊÔÚÂÙÈο ÛÙ¿‰È· Ù˘ ·Ó¿Ù˘Í˘ ÙˆÓ ÓÂÊÚÒÓ. ¶Ú¿ÁÌ·ÙÈ, Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤¯Ô˘Ó ·Ó·Ù˘¯ı› Û˘ÛÙ‹Ì·Ù· fiˆ˜ ÙÔ Cre / LoxP ‹ ·ÎfiÌ· ÈÔ ÚfiÛÊ·Ù· Ë Ì¤ıÔ‰Ô˜ Ù˘ ÁÔÓȉȷ΋˜ Û›ÁËÛ˘ Ì ‰›ÎψÓÔ Û˘ÌÏËڈ̷ÙÈÎfi RNA (RNAi), ÔÈ Ôԛ˜ ÂÈÙÚ¤Ô˘Ó ÙËÓ ÂÈÏÔÁ‹ ÙfiÛÔ ÙÔ˘ ÈÛÙÔ‡ fiÛÔ Î·È Ù˘ ¯ÚÔÓÈ΋˜ ÛÙÈÁÌ‹˜ ηٿ ÙËÓ ÔÔ›· Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Ë ·ÂÓÂÚÁÔÔ›ËÛË ÂÓfi˜

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Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ÁÔÓȉ›Ô˘. ∆¤ÙÔÈÔ˘ ›‰Ô˘˜ ÚÔÛÂÁÁ›ÛÂȘ ·Ó·Ì¤ÓÂÙ·È Ó· ‰È¢ڇÓÔ˘Ó ÛËÌ·ÓÙÈο ÙËÓ ˘¿Ú¯Ô˘Û· ÁÓÒÛË Û¯ÂÙÈο Ì ÙÔÓ ÚfiÏÔ ÁÔÓȉ›ˆÓ ÛÙȘ ‰È¿ÊÔÚ˜ ·Ó·Ù˘ÍȷΤ˜ ‰È·‰Èηۛ˜.

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REVIEW ARTICLE

√ÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ: ·›ÙÈ· Î·È ÚfiÏË„Ë ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ 1 ∂ÚÁ·ÛÙ‹ÚÈÔ ¶ÂÈÚ·Ì·ÙÈ΋˜ º·ÚÌ·ÎÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ 2 °’ ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ¶ÂÈÚ·È¿ “∆˙¿ÓÂÈÔ” AÏÏËÏÔÁÚ·Ê›·: ∞fiÛÙÔÏÔ˜ ∑¿ÚÚÔ˜ ∆.£.14172, ∆.∫.115 10, ∞ı‹Ó· ∂-mail: azarros@med.uoa.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 04-03-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 10-02-2006

∫. ∫·ÏÔ‹Ù·1, ∞. ∑¿ÚÚÔ˜1, ∞. ∞ÓÙˆÓfiÔ˘ÏÔ˜2, π.™. ¶··‰fiÔ˘ÏÔ˜1

¶ÂÚ›ÏË„Ë: ∆· ·Ù˘¯‹Ì·Ù· Ô˘ ÛËÌÂÈÒÓÔÓÙ·È ÂÓÙfi˜ ÙÔ˘ ÔÈÎÈ·ÎÔ‡ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ ÛÙÔÓ ·ÔηÏÔ‡ÌÂÓÔ “·ÓÂÙ˘Á̤ÓÔ ÎfiÛÌÔ”, ·ÔÙÂÏÔ‡Ó Ì›· ÛËÌ·ÓÙÈ΋ ·ÈÙ›· ÓÔÛËÚfiÙËÙ·˜, ÚÔÛˆÚÈÓ‹˜ ‹ ÌfiÓÈÌ˘ ·Ó·ËÚ›·˜ Î·È ıÓËÙfiÙËÙ·˜ ÛÙȘ Ó·ڤ˜ ËÏÈ˘, ÙÔ ÎÔÈÓˆÓÈÎfi Î·È ÔÈÎÔÓÔÌÈÎfi ÎfiÛÙÔ˜ ÙˆÓ ÔÔ›ˆÓ ηٿ ÁÂÓÈ΋ ÔÌÔÏÔÁ›· - ˘ÔÙÈÌ¿Ù·È. ™ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË Û˘ÓÔ„›˙ÔÓÙ·È: ·) Ù· ÛËÌ·ÓÙÈÎfiÙÂÚ· ·›ÙÈ· ÚfiÎÏËÛ˘ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ÛÙÔÓ ¯ÒÚÔ ÙÔ˘ ÛÈÙÈÔ‡ Î·È ‚) Ù· ‚·ÛÈÎfiÙÂÚ· Ú·ÎÙÈο Î·È ıˆÚËÙÈο Ï·›ÛÈ· ÁÈ· ÙË Ï‹„Ë Ô˘ÛÈ·ÛÙÈÎÒÓ Ì¤ÙÚˆÓ Ì ÛÎÔfi ÙËÓ ÚfiÏË„‹ ÙÔ˘˜. ™ÙÔÓ ÙÔ̤· Ù˘ ÚfiÏ˄˘ ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ, ¤Ú· ·fi ÙËÓ ÈÛÙ‹ Î·È ·‰È¿ÏÂÈÙË ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÓÔÌÔıÂÙÈÎÔ‡ Ï·ÈÛ›Ô˘ Î·È ÙˆÓ ÚԉȷÁÚ·ÊÒÓ ·ÛÊ·Ï›·˜, ‚·ÛÈÎfi ·Ú¿ÁÔÓÙ· ÚÔfi‰Ô˘ ·ÔÙÂÏ› Î·È Ë ·ÏÏ·Á‹ ÓÔÔÙÚÔ›·˜: ·) ÛÙÔ˘˜ ÁÔÓ›˜ (ˆ˜ ¿ÌÂÛÔ˘˜ Î·È Î·ıËÌÂÚÈÓÔ‡˜ ÂȂϤÔÓÙ˜ ÙˆÓ ·È‰ÈÒÓ ÙÔ˘˜), ‚) ÛÙÔ˘˜ ÁÈ·ÙÚÔ‡˜ (ˆ˜ ·Úԯ›˜ ÏËÚÔÊfiÚËÛ˘ Î·È ÊÔÚ›˜ Ù˘ ÁÓÒÛ˘) Î·È Á) ÛÙËÓ ÔÏÈÙ›· (ˆ˜ ÓÔÌÔı¤ÙË Î·È ÂÏÂÁÎÙ‹ ÂÊ·ÚÌÔÁ‹˜ Ù˘ ÓÔÌÈÌfiÙËÙ·˜ ÌÂ Ù˘ÊÏfi ÁÓÒÌÔÓ· ÙËÓ ˘Á›· ÙÔ˘ ÏËı˘ÛÌÔ‡). §¤ÍÂȘ ÎÏÂȉȿ: ¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙÔ Û›ÙÈ, ·›ÙÈ·, ÚfiÏË„Ë, ·ÛÊ¿ÏÂÈ·, ÂÎ·›‰Â˘ÛË, ÓÔÌÔıÂÛ›·, ÓÔÔÙÚÔ›·, ÂÊ·ÚÌÔÁ‹.

Domestic environment: causes and prevention of childhood accidents 1 Department of Experimental Pharmacology, Medical School, University of Athens 2 3rd Surgical Department, “Tzaneio” General Hospital of Piraeus Correspondence: Apostolos Zarros Po. Box: 14172, 115 10, Athens ∂-mail: azarros@med.uoa.gr Date of submission: 04-03-2005 Date of approval: 10-02-2006

K. Kalopita1, A. Zarros1, A. Antonopoulos2, J.S. Papadopulos1

Abstract: In the so-called “developed world”, domestic accidents constitute a significant cause of morbidity, temporary or permanent disability and death in early life, the social and economic costs of which are generally underestimated. This is a review of: a) the most common causes of childhood accidents in the home and b) the main theoretical and practical aspects of their avoidance. The prevention of domestic childhood accidents necessitates more than strict and continuous enforcement of the relevant laws and safety standards; it also requires a significant change in attitude among: a) parents (who maintain the direct responsibility for the safety of their infants), b) doctors (who act as knowledge carriers and information providers) and c) the State (as legislator and auditor of enforcement of the law in favour of the health of its citizens).

Key words: Domestic childhood accidents, causes, prevention, safety, instruction, legislation, attitude, enforcement

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¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ

(65,7%) Î·È ·ÎÔÏÔ‡ıˆ˜ ÛÙÔÓ ‰ÚfiÌÔ (25,4%) Î·È ÛÙÔ Û¯ÔÏÂ›Ô (6,1%). ∆· ÂÚÈÛÛfiÙÂÚ· ·È‰Èο ·Ù˘¯‹Ì·Ù· ÛËÌÂÈÒıËÎ·Ó Î˘Ú›ˆ˜ ·ÚÁ¿ ÙÔ ·fiÁÂ˘Ì· (49,6%), ÈÔ Û˘¯Ó¿ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ Î·ÏÔηÈÚÈÓÒÓ ÌËÓÒÓ Î·È ÙˆÓ Û¯ÔÏÈÎÒÓ ‰È·ÎÔÒÓ (38,1%). ¶ÚÔηÏ› ȉȷ›ÙÂÚË ÂÓÙ‡ˆÛË ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ù· ÂÚÈÛÛfiÙÂÚ· ·È‰È¿ Û˘Óԉ‡ÔÓÙ·Ó fiÙ·Ó Û˘Ó¤‚Ë ÙÔ ·Ù‡¯ËÌ·, Ì ÌÂÁ·Ï‡ÙÂÚË Û˘¯ÓfiÙËÙ· Û˘Ì‚¿ÓÙˆÓ ÛÙ· ·ÁfiÚÈ· (55,4%) Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ· (44,6%) (3). ∂›Û˘, ¤¯ÂÈ ·Ô‰Âȯı› fiÙÈ ÔÈÎÔÁ¤ÓÂȘ Ì ¯·ÌËÏfiÙÂÚÔ ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎfi Â›Â‰Ô ÙËÚÔ‡Û·Ó ÏÈÁfiÙÂÚ· ̤ÙÚ· ·ÛÊ·Ï›·˜ ÁÈ· ÙËÓ ÚÔÛÙ·Û›· ÙˆÓ ·È‰ÈÒÓ ÙÔ˘˜, ÂÓÒ Ï›ÁÔÈ ÁÔÓ›˜ ›¯·Ó Ù· ·È‰È¿ ˘fi ÙËÓ ·‰È¿ÏÂÈÙË Â›‚Ï„‹ ÙÔ˘˜ (4). ∞ÍÈÔÛËÌ›ˆÙÔ Â›Ó·È, Â›Û˘, ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ÙÚ·˘Ì·ÙÈÛÌÔ› Á›ÓÔÓÙ·È Û ¤Ó· ÂÚÈ‚¿ÏÏÔÓ ÙÔ ÔÔ›Ô ıˆÚÔ‡ÓÙ·Ó ·ÛʷϤ˜ Û‡Ìʈӷ Ì ٷ ÎÚÈÙ‹ÚÈ· ÙˆÓ ÁÔÓ¤ˆÓ. ™˘ÓÂÒ˜, ÛÙÔ Ï·›ÛÈÔ Ù˘ ÚfiÏ˄˘ ı· Ú¤ÂÈ Ó· ‰Ôı› ȉȷ›ÙÂÚË ¤ÌÊ·ÛË ÛÙËÓ ·Ó·ÁÓÒÚÈÛË ÙˆÓ Èı·ÓÒÓ ÎÈÓ‰‡ÓˆÓ Ô˘ ÂÏÏÔ¯Â‡Ô˘Ó Û οı ÛÙ¿‰ÈÔ ·Ó¿Ù˘Í˘ ÙÔ˘ ·È‰ÈÔ‡ (5). ∆· ̤ÙÚ· Ô˘ ı· Ú¤ÂÈ Ó· ÏËÊıÔ‡Ó ÚÔ˜ ·˘Ù‹ ÙËÓ Î·Ù‡ı˘ÓÛË, ı· Ú¤ÂÈ Ó· ÛÙÔ¯Â‡Ô˘Ó ÛÂ: ·) ÚÔÛ·ÚÌÔÁ‹ Î·È ·ÛÊ·Ï‹ ‰È·ÌfiÚʈÛË ÙÔ˘ ÔÈÎÈ·ÎÔ‡ ÂÚÈ‚¿ÏÏÔÓÙÔ˜, ‚) ÂÓ›Û¯˘ÛË Ù˘ ÓÔÌÔıÂÛ›·˜, ηıÒ˜ Î·È Á) ÂÎ·È‰Â˘ÙÈ΋ ̤ÚÈÌÓ· (6). ∂ÍÂÙ¿˙ÔÓÙ·˜ Ù· ÛÙ·ÙÈÛÙÈο ‰Â‰Ô̤ӷ Ô˘ ·ÊÔÚÔ‡Ó ÛÙËÓ ∂ÏÏ¿‰·, ·Í›˙ÂÈ Ó· Á›ÓÂÈ ·Ó·ÊÔÚ¿ Û ̛· ÂȉËÌÈÔÏÔÁÈ΋ ¤Ú¢ӷ Ô˘ ‰ÈÂÍ‹¯ıË ·fi ÙÔ ∂ÚÁ·ÛÙ‹ÚÈÔ ÀÁÈÂÈÓ‹˜ Î·È ∂ȉËÌÈÔÏÔÁ›·˜ Ù˘ π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ∞ıËÓÒÓ (7). ∏ ¤Ú¢ӷ Ú·ÁÌ·ÙÔÔÈ‹ıËΠ۠·È‰È¿ ËÏÈΛ·˜ 5-14 ÂÙÒÓ (ηÙÔ›ÎÔ˘˜ ∞ıËÓÒÓ), Ù· ÔÔ›· ‰È·ÎÔÌ›ÛÙËÎ·Ó ÛÙ· Â›ÁÔÓÙ· ÙÌ‹Ì·Ù· ‰‡Ô ¶·ÓÂÈÛÙËÌÈ·ÎÒÓ ¡ÔÛÔÎÔÌ›ˆÓ ¶·›‰ˆÓ (·fi ÙÔÓ ¢ÂΤ̂ÚÈÔ 1993 ¤ˆ˜ Î·È ÙÔÓ ∞Ú›ÏÈÔ 1994) ÌÂÙ¿ ·fi ÙÚ·˘Ì·ÙÈÛÌfi. ¢ÈÂÚ¢ӋıËΠÙÔ Â¿Ó Î·È Û ÔÈÔ ÔÛÔÛÙfi ‰È¿ÊÔÚ˜ ‚ÈÔÎÔÈÓˆÓÈΤ˜ ·Ú¿ÌÂÙÚÔÈ ·ÔÙÂÏÔ‡Ó ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ·ÛÊ¿ÏÂÈ· ÙˆÓ ·È‰ÈÒÓ. ∆· ·ÔÙÂϤÛÌ·Ù· Ù˘ ¤Ú¢ӷ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë Èı·ÓfiÙËÙ· ÂÓfi˜ ·Ù˘¯‹Ì·ÙÔ˜ Â›Ó·È ˘„ËÏfiÙÂÚË Û ·È‰È¿: ·) Ì Ó·Úfi ·Ù¤Ú·, ‚) Ì ÌËÙ¤Ú· Ì ÌË-Â·ÁÁÂÏÌ·ÙÈ΋ ··Û¯fiÏËÛË, Á) Ì ˘„ËÏfiÙÂÚË ÛÂÈÚ¿ ÁÂÓÓ‹Ûˆ˜, ‰) Ì ÂÈÎÚ·Ù¤ÛÙÂÚË ÙËÓ Â›‚ÏÂ„Ë ·fi ÙÚ›ÙÔ˘˜, ηıÒ˜ Î·È Â) Ì ÈÛÙÔÚÈÎfi ÚÔËÁÔ‡ÌÂÓÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ (7). ¶ÚfiÛÊ·ÙË ÌÂϤÙË ÙˆÓ Petridou Î·È Û˘Ó (8) ¤‰ÂÈÍ fiÙÈ Û ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÂÓfi˜ ¤ÙÔ˘˜ ÙÚ·˘Ì·Ù›˙ÂÙ·È ÔÛÔÛÙfi 28% ÙˆÓ ·È‰ÈÒÓ (ËÏÈΛ·˜ 0-14 ÂÙÒÓ) ÌÈ·˜ fiÏ˘ fiˆ˜ ÙÔ µÂÏÂÛÙ›ÓÔ,

Ì ÙËÓ ÏÂÈÔ„ËÊ›· ÙˆÓ ÙÚ·˘Ì·ÙÈÛÌÒÓ Ó· ·ÔÙÂÏÔ‡Ó ÙÒÛÂȘ. ™ÙËÓ ›‰È· ÌÂϤÙË, ÔÈ ÂÚ¢ÓËÙ¤˜ Û˘Û¯ÂÙ›˙Ô˘Ó ÙË ÌÈÎÚ‹ ËÏÈΛ· ÙˆÓ ÁÔÓ¤ˆÓ Î·È ÙÔ ¯·ÌËÏfi ÌÔÚʈÙÈÎfi Â›Â‰Ô ·˘ÙÒÓ, Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÚfiÎÏËÛ˘ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ.

∏ÏÈÎȷ΋ ηٷÓÔÌ‹ ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ¶ÚÔÛ¯ÔÏÈ΋ ËÏÈΛ· (0-5 ÂÙÒÓ) ™Â ·˘Ù‹ ÙËÓ ËÏÈΛ· ÔÈ ÙÒÛÂȘ Â›Ó·È 2 ÊÔÚ¤˜ Û˘¯ÓfiÙÂÚ˜ ·fi fi,ÙÈ ÛÙ· ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ (Ì ÙȘ ÂÚÈÛÛfiÙÂÚ˜ Ó· Ï·Ì‚¿ÓÔ˘Ó ¯ÒÚ· ÂÓÙfi˜ ÙÔ˘ ÛÈÙÈÔ‡ Î·È Ó· Û¯ÂÙ›˙ÔÓÙ·È Û˘Ó‹ıˆ˜ Ì ÙËÓ Â›ψÛË ‹ ÙȘ ÛοϘ). √È ‰ËÏËÙËÚÈ¿ÛÂȘ Â›Ó·È Û˘¯ÓfiÙÂÚ˜, ÂÓÒ Û ·˘Ù‹ ÙËÓ ËÏÈΛ· ·Ú·ÙËÚÂ›Ù·È Î·È ÙÔ ˘„ËÏfiÙÂÚÔ ÔÛÔÛÙfi ÂÁη˘Ì¿ÙˆÓ. µ¤‚·È·, ‰ÂÓ ·Ô˘ÛÈ¿˙Ô˘Ó Î·È Ù· Û˘Ì‚¿ÓÙ· Ì ηٿÔÛË Í¤ÓˆÓ ÛˆÌ¿ÙˆÓ ‹ ÂÈÛ·ÁˆÁ‹ Í¤ÓˆÓ ÛˆÌ¿ÙˆÓ ÛÙË Ì‡ÙË, ÙÔÓ ·ÎÔ˘ÛÙÈÎfi fiÚÔ ‹ ÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÂÚÈÓ¤Ô˘ (9,10). ™¯ÔÏÈ΋ ËÏÈΛ· (6-13 ÂÙÒÓ) ¢È·ÈÛÙÒÓÂÙ·È fiÙÈ Û ·˘Ù‹ ÙËÓ ËÏÈΛ· Ù· ·Ù˘¯‹Ì·Ù· Ô˘ Ï·Ì‚¿ÓÔ˘Ó ¯ÒÚ· ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ ÌÂÈÒÓÔÓÙ·È (Ì ÌÈÎÚfi ÔÛÔÛÙfi ÂÁη˘Ì¿ÙˆÓ Î·È ‰ËÏËÙËÚÈ¿ÛˆÓ), ‰›ÓÔÓÙ·˜ ÙË ı¤ÛË ÙÔ˘˜ Û ¤Ó·Ó ÌÂÁ¿ÏÔ ·ÚÈıÌfi ÙÚÔ¯·›ˆÓ ·Ù˘¯ËÌ¿ÙˆÓ (10). ¶ÚÔÂÊË‚È΋ Î·È ÂÊË‚È΋ ËÏÈΛ· (13-19 ÂÙÒÓ) ™˘¯Ó¿ Â›Ó·È Ù· ·Ù˘¯‹Ì·Ù· ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÚÔfiÓËÛ˘ ‹ ÁÂÓÈÎfiÙÂÚ· ηٿ ÙËÓ ¿ıÏËÛË. ∂›Û˘, Û ·˘Ù‹ ÙËÓ ËÏÈΛ· ˘¿Ú¯ÂÈ ÌÂÁ¿ÏË Èı·ÓfiÙËÙ· Ó· ÙÚ·˘Ì·ÙÈÛÙ› Ô ¤ÊË‚Ô˜ ˆ˜ Ô‰ËÁfi˜ ‹ ÂÈ‚¿Ù˘ Ô¯‹Ì·ÙÔ˜, ÁÂÁÔÓfi˜ Ô˘ ÂÈÙ›ÓÂÙ·È ·fi ÙËÓ ˘ÂÚ‚ÔÏÈ΋ ¯Ú‹ÛË ·ÏÎÔfiÏ Î·È Ó·ÚΈÙÈÎÒÓ, ·ÏÏ¿ Î·È ÙËÓ ÂÊË‚È΋ ·ÚÔÚÌËÙÈÎfiÙËÙ· (10).

¶·Ú¿ÁÔÓÙ˜ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙËÓ ÚfiÎÏËÛË ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ∫¿ı ·È‰›, Û ·ÓÙ›ıÂÛË Ì ÙÔÓ ÂÓ‹ÏÈÎÔ, ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ¤ÏÏÂÈ„Ë ›ڷ˜, ˆÚÈÌfiÙËÙ·˜ Î·È ·ÓÙ›Ï˄˘ ÙÔ˘ ÎÈÓ‰‡ÓÔ˘, ÂÓÒ ‰È·Î·Ù¤¯ÂÙ·È ·fi ¤ÌÊ˘ÙË ÂÈı˘Ì›· (ÂÚȤÚÁÂÈ·) Ó· ÁÓˆÚ›ÛÂÈ, Ó· ‰ÔÎÈÌ¿ÛÂÈ Î·È Ó· ÂÈÚ·Ì·ÙÈÛÙ› Ì ٷ ·ÓÙÈΛÌÂÓ· Ô˘ ÙÔ ÂÚÈ‚¿ÏÏÔ˘Ó. √ ÂÓ‹ÏÈÎÔ˜ Û˘¯Ó¿ ıˆÚ› fiÙÈ ÙÔ ÌÈÎÚfi ·È‰› Û˘ÌÂÚÈʤÚÂÙ·È ¶·È‰È·ÙÚÈ΋ 2006;69:268-277

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∫. ∫·ÏÔ‹Ù· Î·È Û˘Ó.

·ÂÚ›ÛÎÂÙ·. ∆Ô Ó‹ÈÔ, fï˜, ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂÍÂÚ¢ӋÛÂÈ Î¿ı Ù˘¯‹ ÙÔ˘ ·ÓÙÈÎÂÈ̤ÓÔ˘ Ô˘ ÂÚÈÂÚÁ¿˙ÂÙ·È, ıˆÚ› ‡ÛÙÔ¯Ô Ó· ÙÔ Ê¤ÚÂÈ ÛÙÔ ÛÙfiÌ· ÙÔ˘ (11). ∞ÔÙÂÏ› ‰Â, ÛÙÔÈ¯Â›Ô Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ÙÔ˘ ·Ó¿Ù˘Í˘ Ë ÚÔÛ¿ıÂÈ· Ó· ‰È¢ڇÓÂÈ ÙÔ ÔÙÈÎfi ÙÔ˘ ‰›Ô (̤۷ ÛÙÔÓ ÌÈÎÚfiÎÔÛÌfi ÙÔ˘) ̤ۈ Ù˘ ·Ó·ÚÚ›¯ËÛ˘ Û ¤ÈÏ· Î·È ·Ú¿ı˘Ú·, ÂÓÒ - ÏfiÁˆ Ù˘ ·Ó·ÙÔÌÈ΋˜ ÙÔ˘ ηٷÛ΢‹˜ (¯·ÌËÏfiÙÂÚÔ Î¤ÓÙÚÔ ‚¿ÚÔ˘˜ ÏfiÁˆ ·Ó·ÛÙ‹Ì·ÙÔ˜) - ÙÔ Ó‹ÈÔ ¯¿ÓÂÈ Â‡ÎÔÏ· ÙËÓ ÈÛÔÚÚÔ›· ÙÔ˘ fiÙ·Ó Û·‚ÂÈ (11,12). ∫·ıÔÚÈÛÙÈ΋˜ ÛËÌ·Û›·˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÓ¤¯ÔÓÙ·È ÛÙËÓ ÚfiÎÏËÛË ·Ù˘¯‹Ì·ÙÔ˜ Â›Ó·È ÙfiÛÔ Ë ËÏÈΛ· ÙÔ˘ ·È‰ÈÔ‡, fiÛÔ Î·È ÙÔ Ê‡ÏÔ ÙÔ˘. ∆· ·ÁfiÚÈ· Â›Ó·È ÈÔ ÂÈÚÚÂ‹ Û ·Ù˘¯‹Ì·Ù· ÏfiÁˆ Ù˘ ·Ó‹Û˘¯Ë˜ Î·È ÈÔ ÂÈıÂÙÈ΋˜ ʇÛ˘ ÙÔ˘˜. ∂›Ó·È ÁÂÁÔÓfi˜ fiÙÈ ÛÙÔÓ ‰Â‡ÙÂÚÔ ¯ÚfiÓÔ Ù˘ ˙ˆ‹˜ ÙÔ˘˜, Ù· ·È‰È¿ Ù˘ ÚÔÛ¯ÔÏÈ΋˜ ËÏÈΛ·˜ ¤¯Ô˘Ó ÙËÓ Ù¿ÛË Ó· ÂÍÂÚ¢ÓÔ‡Ó „¿¯ÓÔÓÙ·˜ ÁÈ· ÎÚ˘Ì̤ӷ ‹ ¿ÁÓˆÛÙ· ·ÓÙÈΛÌÂÓ· ÛÙÔ Û›ÙÈ (12). ∞ӷχÔÓÙ·˜ ÙËÓ „˘¯ÔÏÔÁÈ΋ ·ÈÙÈfiÙËÙ· ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ, Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ ÙÔ ·È‰› ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÛΤ„Ë ·ÓÒÚÈÌË, ÚÈ„ÔΛӉ˘ÓË Î·È ÂÁˆÎÂÓÙÚÈ΋. ∂ÓÂÚÁ›, ‰ËÏ·‰‹, Ì ÁÓÒÌÔÓ· ÙËÓ ÈηÓÔÔ›ËÛË Ù˘ ÂÚȤÚÁÂÈ¿˜ ÙÔ˘. ∂Ô̤ӈ˜, Ë Â›‚ÏÂ„Ë ÙˆÓ ÁÔÓ¤ˆÓ ı· Ú¤ÂÈ Ó· Â›Ó·È ¿ÌÂÛË Î·È Ô˘ÛÈ·ÛÙÈ΋, ·Ú·Ì¤ÓÔÓÙ·˜ ¿ÓÙ· Û ÂÁÚ‹ÁÔÚÛË, ηıÒ˜ ÙÔ ·È‰› ÎÈÓÂ›Ù·È Ì ¢ÂÏÈÍ›· Î·È Ù·¯‡ÙËÙ·, ‚¿˙ÔÓÙ·˜ ˆ˜ ÛÙfi¯Ô˘˜ ·ÓÙÈΛÌÂÓ· Ô˘ ‰‡ÛÎÔÏ· ÌÔÚ› Ó· ·ÓÙÈÏËÊı› Ô ÂÓ‹ÏÈÎÔ˜ (13). ™Ù· ·È‰È¿ ËÏÈΛ·˜ ÌÈÎÚfiÙÂÚ˘ ÙˆÓ 2 ÂÙÒÓ, Ë Â›‚ÏÂ„Ë Â›Ó·È ··Ú·›ÙËÙË (‰ÂÓ ı· Ú¤ÂÈ fï˜ Ó· ·ÁÁ›˙ÂÈ Î·È Ù· fiÚÈ· ÙÔ˘ ˘ÂÚÚÔÛٷ٢ÙÈÛÌÔ‡, ηıÒ˜ Ô ÙÂÏÂ˘Ù·›Ô˜ ηıÈÛÙ¿ Ù· ·È‰È¿ ÈÔ ÂÈÚÚÂ‹ Û ·Ù˘¯‹Ì·Ù· ÏfiÁˆ ·ÙÂÏÔ‡˜ ·Ó¿Ù˘Í˘ ÙˆÓ ·ÓÙ·Ó·ÎÏ·ÛÙÈÎÒÓ ¤Ó·ÓÙÈ ÙˆÓ ÎÈÓ‰‡ÓˆÓ ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜). ∂›Û˘, ȉȷ›ÙÂÚË ÛËÌ·Û›· Ú¤ÂÈ Ó· ‰›ÓÂÙ·È Û ·È‰È¿ Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ì·ıËÛȷΤ˜ ‹ ÎÈÓËÙÈΤ˜ ‰˘ÛÎÔϛ˜, ·‰ÂÍÈfiÙËÙ· ‹ ÂÌÊ·Ó›˙Ô˘Ó ÂÈÏËÙÈΤ˜ ÎÚ›ÛÂȘ, ηıÒ˜ ¤¯Ô˘Ó ÛËÌÂȈı› ÔÏÏ¿ ÂÁη‡Ì·Ù· (14) ‹ ·ÎfiÌË Î·È Ê·ÈÓfiÌÂÓ· ·ÛÊ˘Í›·˜, ÚÔηÏÔ‡ÌÂÓ· ÁÈ· ·Ú¿‰ÂÈÁÌ· - ·fi ÂÍ·ÚÙ‹Ì·Ù· ÎÏ›Ó˘ Ô˘ ·¤ÙÚÂ·Ó ÙËÓ ÙÒÛË Û ·È‰È¿ Ì ‰È·ÓÔËÙÈ΋ ηı˘ÛÙ¤ÚËÛË (15). Ÿˆ˜ ÚԷӷʤÚıËÎÂ, Ë Ê˘ÛÈ΋ ·ÚÔ˘Û›· οÔÈÔ˘ ÂÓ‹ÏÈη ÛÙÔÓ ¯ÒÚÔ Ô˘ ‚Ú›ÛÎÂÙ·È ÙÔ ·È‰›, ‰ÂÓ ·ÔÙÂÏ› ¿ÓÙ· ·ÔÙÚÂÙÈÎfi ·Ú¿ÁÔÓÙ· ÁÈ· ÙËÓ ÚfiÎÏËÛË ·Ù˘¯‹Ì·ÙÔ˜. ∆Ô ÔÙÈÎfi ‰›Ô ÙÔ˘ ·È‰ÈÔ‡ ÂÚÈÔÚ›˙ÂÙ·È Û 70-80 cm ·fi ÙÔ ¤‰·ÊÔ˜, ÔfiÙÂ Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ·ÓÙÈÏËÊı› ηÓ›˜ ÙÔ ·ÓÙÈΛÌÂÓÔ Ô˘ ·˘Ùfi ¤¯ÂÈ ı¤ÛÂÈ ¶·È‰È·ÙÚÈ΋ 2006;69:268-277

ˆ˜ ÛÙfi¯Ô ÙÔ˘ Î·È Ó· ÚԂϤ„ÂÈ ÙȘ ÎÈÓ‹ÛÂȘ ÙÔ˘, ȉ›ˆ˜ Â¿Ó ÚfiÎÂÈÙ·È ÁÈ· οÔÈÔ ËÏÈÎȈ̤ÓÔ ¿ÙÔÌÔ. ŒÙÛÈ, ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔÚ¤˜, ÙÔ ·È‰› ‰Ú· Ù·¯‡Ù·Ù· Î·È ÙÔ ·Ù‡¯ËÌ· Ï·Ì‚¿ÓÂÈ ¯ÒÚ· ̤۷ Û ÎÏ¿ÛÌ·Ù· ÙÔ˘ ‰Â˘ÙÂÚÔϤÙÔ˘. ∆Ô Ê˘ÛÈÎfi ÂÚÈ‚¿ÏÏÔÓ ıˆÚÂ›Ù·È ·Ú¿ÁÔÓÙ·˜ ηıÔÚÈÛÙÈ΋˜ ÛËÌ·Û›·˜, ηıÒ˜ Û ·˘Ùfi ÌÔÚÔ‡Ó Ó· Á›ÓÔ˘Ó ÔÏϤ˜ ·ÚÂÌ‚¿ÛÂȘ, .¯. ÁÈ· ¤Ó· ·ÛʷϤ˜ Û›ÙÈ ¯ˆÚ›˜ ·Á›‰Â˜ Î·È ÎÈÓ‰‡ÓÔ˘˜ ÁÈ· ÙÔ ·È‰› (16). √ ÎfiÛÌÔ˜ ÛÙÔÓ ÔÔ›Ô ˙ÂÈ Î·È ·Ó·Ù‡ÛÛÂÙ·È ¤Ó· ·È‰› Â›Ó·È Û¯Â‰È·Ṳ̂ÓÔ˜ ·fi ÂÓ‹ÏÈΘ ÁÈ· ÂÓ‹ÏÈΘ, Î·È fi¯È (ηÈ) ÁÈ· ·È‰È¿. ∏ ·Ô˘Û›· ηٷÛ΢·ÛÙÈÎÒÓ Ì¤ÙÚˆÓ ÚfiÏ˄˘ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ÛÙÔ˘˜ ·ÓÂÏ΢ÛÙ‹Ú˜, ÛÙ· ·Ú¿ı˘Ú·, ÛÙȘ Á˘¿ÏÈÓ˜ ÌÂÛfiÔÚÙ˜, ÛÙ· Á˘¿ÏÈÓ· Ì·ÏÎfiÓÈ·, ÛÙÔ ‡„Ô˜ Ô˘ ¤¯Ô˘Ó Ù· οÁÎÂÏ· Î·È ÛÙȘ Îϛ̷Θ, ÔÊ›ÏÂÙ·È ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ ·˘Ù¿ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È Ì ÁÓÒÌÔÓ· ÙËÓ Ù·‡ÙÈÛË Ì ÙËÓ ·ÈÛıËÙÈ΋ Ù˘ ÂÔ¯‹˜ Î·È fi¯È ÙËÓ ÚÔÛÙ·Û›· ÙˆÓ ÂÓÔ›ÎˆÓ Ô˘ ÊÈÏÔÍÂÓÔ‡Ó. ∂ȉÈÎfiÙÂÚ·, ÛÙË ¯ÒÚ· Ì·˜ ˘¿Ú¯ÂÈ Ë Ù¿ÛË Ó· ÌÂÙ·ÙÚ¤ÂÙ·È Ë ÎÔ˘˙›Ó· (Ì fiÏÔ˘˜ ÙÔ˘˜ ÎÈÓ‰‡ÓÔ˘˜ Ô˘ ·˘Ù‹ ÂÓ¤¯ÂÈ) Û ‰ˆÌ¿ÙÈÔ ·Ó¿ıÚ„˘ ÙˆÓ ·È‰ÈÒÓ. ∂¿Ó ·Ó·ÏÔÁÈÛÙ› ηÓ›˜ ÙȘ ·Á›‰Â˜ Ô˘ ÂÏÏԯ‡ÂÈ ÁÈ· ÙÔ ·È‰› ·˘Ùfi˜ Ô ¯ÒÚÔ˜ (ËÏÂÎÙÚÈΤ˜ Û˘Û΢¤˜, η˘Ù¿ ˘ÁÚ¿, ·È¯ÌËÚ¿ ·ÓÙÈΛÌÂÓ·, ·ÔÚÚ˘·ÓÙÈο Î.¿.), ‰ÂÓ ı· Ú¤ÂÈ Ó· ·ÔÙÂÏ› ¤ÎÏËÍË ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë ÎÔ˘˙›Ó· ·ÔÙÂÏ› ÙÔÓ ¯ÒÚÔ ÂÓÙfi˜ ÙÔ˘ ÛÈÙÈÔ‡ fiÔ˘ Á›ÓÔÓÙ·È Û˘¯ÓfiÙÂÚ· ·Ù˘¯‹Ì·Ù· (17).

¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ ™ÙÔÓ ¶›Ó·Î· 1, fiÔ˘ ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ë ‰È·Î‡Ì·ÓÛË ÙÔ˘ Û˘ÓÙÂÏÂÛÙ‹ ÎÈÓ‰‡ÓÔ˘ ı·Ó¿ÙÔ˘ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ‰È·ÊfiÚˆÓ Î·Ù·ÛÙ¿ÛÂˆÓ Û ¢ËÌÂÚÔ‡Û˜ ‰˘ÙÈΤ˜ ÎÔÈӈӛ˜, Ê·›ÓÂÙ·È Ë ı¤ÛË Ô˘ η٤¯ÂÈ ÙÔ ÔÈÎÈ·Îfi ·Ù‡¯ËÌ· (18). ™ÙÔÓ ¶›Ó·Î· 2 ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ë Ì¤ÛË ÂÙ‹ÛÈ· ıÓËÛÈÌfiÙËÙ· ¶›Ó·Î·˜ 1. ™˘ÓÙÂÏÂÛÙ‹˜ ÎÈÓ‰‡ÓÔ˘ ı·Ó¿ÙÔ˘ ‰˘ÙÈÎÒÓ ÎÔÈÓˆÓÈÒÓ (18) ∞ÈÙÈÔÏÔÁ›· ∫¿ÓÈÛÌ· (1 ·Î¤ÙÔ/Ë̤ڷ) ∫·ÚΛÓÔ˜ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ ∫·Ù·Ó¿ÏˆÛË ·ÏÎÔÔÏÔ‡¯ˆÓ ∆ÚÔ¯·›Ô ·Ù‡¯ËÌ· √ÈÎÈ·Îfi ·Ù‡¯ËÌ· £‡Ì· ÙÚÔ¯·›Ô˘ ˆ˜ Â˙fi˜ ¢ÔÏÔÊÔÓ›· ∞ÂÚÔÔÚÈÎfi ·Ù‡¯ËÌ·

∆ÈÌ‹ Û˘ÓÙÂÏÂÛÙ‹ 7.932 1.008 591 216 182 47 24 2

271

¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ

¶›Ó·Î·˜ 2. ª¤ÛË ÂÙ‹ÛÈ· ıÓËÛÈÌfiÙËÙ· ·fi ·Ù˘¯‹Ì·Ù· (ª£) ·Ó¿ 1.000.000 ¿ÙÔÌ·, ·Ó¿ÏÔÁ· Ì ÙËÓ ·ÈÙ›· ÙÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ ηٿ ÙËÓ ÂÍ·ÂÙ›· 1990-1995 ÛÙËÓ ∂ÏÏ¿‰· (ÚˆÙÔÁÂÓ‹ ÛÙÔȯ›· Ù˘ ∂ıÓÈ΋˜ ™Ù·ÙÈÛÙÈ΋˜ ÀËÚÂÛ›·˜ Ù˘ ∂ÏÏ¿‰Ô˜) (19) ∫·ÙËÁÔÚ›· ηٿ ICD-9 ∆˘¯·›Â˜ ÙÒÛÂȘ (∂880-∂888) ∞Ù˘¯‹Ì·Ù· ·fi ˘ÚηÁÈ¿ (∂890-∂899) ∆˘¯·›ÔÈ ÓÈÁÌÔ› Î.Ï. (∂910-∂915) ∞Ù˘¯‹Ì·Ù· ·fi fiÏ· (∂922) £ÂÚÌÈο ·Ù˘¯‹Ì·Ù·, Ú‡̷ Î.Ï. (∂923-∂928)

·Ó¿ 1.000.000 ¿ÙÔÌ·, ·fi ÔÚÈṲ̂Ó˜ ηÙËÁÔڛ˜ ·Ù˘¯ËÌ¿ÙˆÓ (‚¿ÛÂÈ Ù˘ Ù·ÍÈÓfiÌËÛ˘ ICD9: International Classification of Diseases-9) ÛÙËÓ ∂ÏÏ¿‰· (19). ∞ÎÔÏÔ˘ı› ÂÚÈÁÚ·Ê‹ ÙˆÓ ÛËÌ·ÓÙÈÎfiÙÂÚˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ ÛËÌÂÈÒÓÔÓÙ·È Ì¤Û· ‹ Á‡Úˆ ·fi ÙÔ Û›ÙÈ (›Ù ·˘Ùfi ÚfiÎÂÈÙ·È ÁÈ· ‰È·Ì¤ÚÈÛÌ· ÔÏ˘Î·ÙÔÈΛ·˜, ›Ù ÁÈ· ÌÔÓÔηÙÔÈΛ· Û ·ÛÙÈÎfi ‹ ·ÁÚÔÙÈÎfi ÂÚÈ‚¿ÏÏÔÓ). ∏ ·‰Ú‹ ·˘Ù‹ Ù·ÍÈÓfiÌËÛË ·ÔÛÎÔ› ÛÙËÓ Î·Ï‡ÙÂÚË ·ÚÔ˘Û›·ÛË ÙˆÓ Èı·ÓÒÓ ÎÈÓ‰‡ÓˆÓ ηٿ ÂÚ›ÙˆÛË, ηıÒ˜ ÙÔ 60-80% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ì¤¯ÚÈ ÙËÓ ËÏÈΛ· ÙˆÓ 4 ÂÙÒÓ, Ï·Ì‚¿ÓÂÈ ¯ÒÚ· ÂÓÙfi˜ ÙÔ˘ ÔÈÎÈ·ÎÔ‡ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ (20). ¢ËÏËÙËÚÈ¿ÛÂȘ √ ¶›Ó·Î·˜ 3 ·ÚÔ˘ÛÈ¿˙ÂÈ ÙËÓ ËÏÈÎȷ΋ ηٷÓÔÌ‹ Â› ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ‰ËÏËÙËÚÈ¿ÛÂˆÓ ÁÈ· Ù· ¤ÙË 1992 Î·È 1999, Ì ‚¿ÛË Ù· ÛÙÔȯ›· Ô˘ ÂÏ‹ÊıËÛ·Ó ·fi ÙÔ ∂ıÓÈÎfi ∫¤ÓÙÚÔ ¢ËÏËÙËÚÈ¿ÛÂˆÓ (21). °›ÓÂÙ·È ·ÓÙÈÏËÙfi fiÙÈ Ù· ·È‰È¿ ËÏÈΛ·˜ 2-4 ÂÙÒÓ Û˘ÁÎÂÓÙÚÒÓÔ˘Ó ÙËÓ ˘„ËÏfiÙÂÚË Û˘¯ÓfiÙËÙ· ‰ËÏËÙËÚÈ¿ÛÂˆÓ ·fi οı ¿ÏÏË (·Ó¿ÏÔÁÔ˘ ‡ÚÔ˘˜) ËÏÈÎȷ΋ ÔÌ¿‰·. ∆Ô 1999 ηٷÁÚ¿ÊËÎ·Ó Û˘ÓÔÏÈο 46.385 ÎÏ‹ÛÂȘ ÚÔ˜ ÙÔ ∂ıÓÈÎfi ∫¤ÓÙÚÔ ¢ËÏËÙËÚÈ¿ÛˆÓ, ÂÎ ÙˆÓ ÔÔ›ˆÓ ÙÔ 57% ›¯Â ˆ˜ ÚԤϢÛË ÙÔ ‰È·Ì¤ÚÈÛÌ· ∞ÙÙÈ΋˜ Î·È ÙÔ ˘fiÏÔÈÔ 43% ÙËÓ ˘fiÏÔÈË ¯ÒÚ·. ∆Ô 2001 ÔÈ ·ÓÙ›ÛÙÔȯ˜ ÎÏ‹ÛÂȘ ‹Ù·Ó 44.809, ÂÎ ÙˆÓ ÔÔ›ˆÓ ÔÛÔÛÙfi 46% ¶›Ó·Î·˜ 3. ∏ÏÈÎȷ΋ ηٷÓÔÌ‹ Â› ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ‰ËÏËÙËÚÈ¿ÛÂˆÓ ÁÈ· Ù· ¤ÙË 1992 Î·È 1999 (21) ∏ÏÈΛ· <1 ¤ÙÔ˘˜ 2-4 ÂÙÒÓ 5-9 ÂÙÒÓ 10-14 ÂÙÒÓ 15-19 ÂÙÒÓ 20+ ÂÙÒÓ ™‡ÓÔÏÔ

1992 (%)

1999 (%)

6,4 33,1 7,0 3,8 5,4 44,3 100

5,6 29,7 7,4 3,6 6,2 47,5 100

ª£ (0-4 ÂÙÒÓ)

ª£ (5-14 ÂÙÒÓ)

6,9 5,4 68,1 0,0 1,9

2,5 2,2 10,5 1,1 1,6

(20.711 ÎÏ‹ÛÂȘ) ·ÊÔÚÔ‡Û Û ·È‰È¿ ËÏÈΛ·˜ ¤ˆ˜ 14 ÂÙÒÓ (21,22). √ ¶›Ó·Î·˜ 4 ·ÚÔ˘ÛÈ¿˙ÂÈ ÙËÓ ÔÛÔÛÙÈ·›· ηٷÓÔÌ‹ ÙˆÓ ·ÈÙÈÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÁÈ· ÙÔ Û‡ÓÔÏÔ ÙˆÓ ‰ËÏËÙËÚÈ¿ÛÂˆÓ (fiÏˆÓ ÙˆÓ ËÏÈÎÈÒÓ) Ô˘ ¤Ï·‚·Ó ¯ÒÚ· ηٿ Ù· ¤ÙË 1961-1966, 19681972, 1980, 1992 Î·È 1999 (20,22). ∆Ô 2001, ÙÔ 46% ÙˆÓ ‰ËÏËÙËÚÈ¿ÛÂˆÓ ÔÊÂÈÏfiÙ·Ó Û ʿÚ̷η, ÙÔ 23% Û ·ÔÚÚ˘·ÓÙÈο, ÙÔ 5% Û ηÏÏ˘ÓÙÈο Î·È ÙÔ 3,3% Û ÁˆÚÁÈο Ê¿Ú̷η (21,23). ∂Î ÙˆÓ Ê·ÚÌ·ÎÔÁÂÓÒÓ ‰ËÏËÙËÚÈ¿ÛˆÓ, ÙÔ 44% ÔÊ›ÏÂÙ·È Û ηٷӿψÛË „˘¯ÔÊ·Ú̿ΈÓ, ·ÓÙÈ‚ÈÔÙÈÎÒÓ Î·È ·Ó·ÏÁËÙÈÎÒÓ (23,24). ∞˘Ùfi ÔÊ›ÏÂÙ·È ÛÙËÓ ·˘ÍË̤ÓË Â˘Ú›· ¯Ú‹ÛË ÙÔ˘˜ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ÙfiÛÔ ·fi ÓÂfiÙÂÚ· fiÛÔ Î·È ·fi ËÏÈÎȈ̤ӷ ¿ÙÔÌ· (Ì ‹ ¯ˆÚ›˜ È·ÙÚÈ΋ Û˘ÓÙ·Á‹), ηıÒ˜ Î·È ÛÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÔÛÔÛÙfi ÂÚ›Ô˘ 15% ·˘ÙÒÓ ÙˆÓ ÂÚÈÙÒÛÂˆÓ ·ÓÙÈÚÔÛˆ‡ÂÈ ·fiÂÈÚ˜ ·˘ÙÔÎÙÔÓ›·˜. ™ÙËÓ Î·ÙËÁÔÚ›· ÙˆÓ ‰ËÏËÙËÚÈ¿ÛÂˆÓ ·fi ›‰Ë ÔÈÎȷ΋˜ ¯Ú‹Ûˆ˜ ı· Ú¤ÂÈ Ó· Á›ÓÂÈ ·Ó·ÊÔÚ¿ ÛÙ· ·ÎfiÏÔ˘ı·: ·) Â›Ó·È Û˘¯Ófi ÙÔ Ê·ÈÓfiÌÂÓÔ ·Ó¿ÌÂÈ͢ ¯ÏˆÚ›Ó˘ Ì Ôͤ· ÛÙÔÓ ¯ÒÚÔ ÙÔ˘ Ì¿ÓÈÔ˘ (¤ÎÏ˘ÛË ¯ÏˆÚ›Ô˘), Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÚfiÎÏËÛË ÛÔ‚·ÚÒÓ ·Ó·Ó¢ÛÙÈÎÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ ÛÙ· ·È‰È¿, ‚) Ë ‰ËÏËÙËÚ›·ÛË Ì ÔÈÓfiÓÂ˘Ì· (Ê·ÈÓfiÌÂÓÔ ÔÍ›·˜ ̤ı˘) ηχÙÂÈ ÌÂÁ¿ÏÔ ·ÚÈıÌfi ÂÚÈÙÒÛÂˆÓ (·ÚÎÂÙ¤˜ Î·È ÛÔ‚·Ú¤˜ Â›Ó·È ÔÈ ‰ËÏËÙËÚÈ¿ÛÂȘ ·fi ÎÔÏfiÓȘ) Î·È Á) Ë ÏÂÈÔ„ËÊ›· ÙˆÓ Î·ÏÏ˘ÓÙÈÎÒÓ Ô˘ ¢ı‡ÓÔÓÙ·È ÁÈ· ÂÚÈÙÒÛÂȘ ‰ËÏËÙËÚ›·Û˘ ÛÙ· ·È‰È¿, ‰ÂÓ Â›Ó·È ÙÔÍÈο (ÂÎÙfi˜ ·fi οÔȘ ‚·Ê¤˜ Ì·ÏÏÈÒÓ). ¢ÂÓ ÈÛ¯‡ÂÈ ÙÔ ›‰ÈÔ fï˜ Î·È ÁÈ· ÙË Ì¿ÛËÛË ÙÛÈÁ¿ÚˆÓ ·fi ‚Ú¤ÊË, Ë ÔÔ›· ÌÔÚ› Ó· ¤¯ÂÈ ‰˘Û¿ÚÂÛÙ· Â·ÎfiÏÔ˘ı· (25). ∏ ÓÈÎÔÙ›ÓË ÛÙ· ÚÔ˚fiÓÙ· ÙÔ˘ ηÓÔ‡ ·ÔÚÚÔÊ¿Ù·È Â‡ÎÔÏ· ·fi ÙÔÓ ‚ÏÂÓÓÔÁfiÓÔ ÙÔ˘ ÛÙfiÌ·ÙÔ˜ Î·È ÙÔ˘ ÂÓÙ¤ÚÔ˘ (Ë ·ÔÚÚfiÊËÛË ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ÔÛfiÙËÙ·/Û‡ÛÙ·ÛË Ù˘ ÓÈÎÔÙ›Ó˘ Î·È ÙÔ pH ÙÔ˘ ηÓÔ‡). ∆· Û˘ÌÙÒÌ·Ù· ÂÍÂÏ›ÛÛÔÓÙ·È Ù·¯¤ˆ˜ (<4 h), Ì ÈÔ ÎÔÈÓfi Û‡Ìو̷ ÙÔÓ ¤ÌÂÙÔ. √ Û›‰ËÚÔ˜ ·ÔÙÂÏ›, Â›Û˘, ÛËÌ·ÓÙÈ΋ ¶·È‰È·ÙÚÈ΋ 2006;69:268-277

272

∫. ∫·ÏÔ‹Ù· Î·È Û˘Ó.

¶›Ó·Î·˜ 4. ¶ÔÛÔÛÙÈ·›· ηٷÓÔÌ‹ ÙˆÓ ·ÈÙÈÒÓ Â› ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ‰ËÏËÙËÚÈ¿ÛÂˆÓ (21,23) ∞Èٛ˜ ‰ËÏËÙËÚÈ¿ÛÂˆÓ º¿Ú̷η ∂›‰Ë ÔÈÎȷ΋˜ ¯Ú‹Ûˆ˜ ∫·ÏÏ˘ÓÙÈο ¢È¿ÊÔÚ˜ ¯ËÌÈΤ˜ Ô˘Û›Â˜ °ÂˆÚÁÈο Ê¿Ú̷η ∆ÚÔʤ˜ ¢‹ÁÌ·Ù· ˙ÒˆÓ º˘Ù¿ ¢È¿ÊÔÚ˜ ¿ÏϘ ·Èٛ˜ ™‡ÓÔÏÔ

1961-1966 (%)

1968-1972 (%)

1980 (%)

1992 (%)

1999 (%)

9,4 13,8 (+) 31,0 (+) (45,8) 100

30,5 11,8 (+) 23,9 (+) (33,8) 100

50,5 15,5 (+) 3,0 (+) (31) 100

42,4 25,1 6,0 1,4 (+) 4,5 (20,6) 100

46,1 22,6 5,2 7,1 3,6 3,2 1,9 0,5 9,8 100

·ÈÙ›· ı·Ó¿ÙÔ˘ ·fi ‰ËÏËÙËÚ›·ÛË Û Ó·ڿ ¿ÙÔÌ·. ∫·ıÒ˜ Ë ÂÚÈÁÂÓÓËÙÈ΋ ıÂÚ·›· Ì ۛ‰ËÚÔ Â›Ó·È Û˘¯Ó‹, Ë ‡·ÚÍË ·˘ÙÒÓ ÙˆÓ ‰ÈÛΛˆÓ (Ô˘ ¤¯Ô˘Ó ÂÌÊ¿ÓÈÛË ·ÚfiÌÔÈ· Ì ÂΛÓË Î·Ú·Ì¤Ï·˜) ÛÙÔ Û›ÙÈ, ÌÔÚ› Ó· ·ÔÙÂϤÛÂÈ Î›Ó‰˘ÓÔ ÁÈ· Ù· ¿ÏÏ· ·È‰È¿ Ù˘ ÌËÙ¤Ú·˜. ª¿ÏÈÛÙ·, ¤Ú¢Ó˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Ë ÂÁ΢ÌÔÛ‡ÓË, ·ÏÏ¿ Î·È Ë ÂÚ›Ô‰Ô˜ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙÔÓ ÙÔÎÂÙfi ·ÔÙÂÏÔ‡Ó ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· Ù· ‹‰Ë ÁÂÓÓËı¤ÓÙ· ·È‰È¿ Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜. ™˘ÁÎÂÎÚÈ̤ӷ, Ù· ·È‰È¿ ÙˆÓ ÔÔ›ˆÓ ÔÈ ÌËÙ¤Ú˜ ΢ÔÊÔÚÔ‡Û·Ó ‹ Á¤ÓÓËÛ·Ó ¤Ó·Ó ·‰ÂÏÊfi/·‰ÂÏÊ‹, ‹Ù·Ó 2 ÊÔÚ¤˜ ÈÔ Èı·Ófi Ó· ‰ËÏËÙËÚÈ·ÛÙÔ‡Ó ·fi Û›‰ËÚÔ Û ۇÁÎÚÈÛË Ì ÂΛӷ ÙˆÓ ÔÔ›ˆÓ Ë ÌËÙ¤Ú· ‰ÂÓ Á¤ÓÓËÛ (26). ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ·Ú·ÙËÚÂ›Ù·È ÙÔ Ê·ÈÓfiÌÂÓÔ Ù˘ ‰ËÏËÙËÚ›·Û˘ ÂÍ·ÈÙ›·˜ Ù˘ ηٿÔÛ˘ Ù·ÌÏÂÙÒÓ Î·ı·ÚÈÛÌÔ‡ ÔÚıÔ‰ÔÓÙÈÎÒÓ ÚÔÛı¤ÛÂˆÓ Î·È Ê·ÎÒÓ Â·Ê‹˜ (27). ∏ Ù˘¯·›· ηٿÔÛ‹ ÙÔ˘˜ ÌÔÚ› Ó· ÔÊ›ÏÂÙ·È ÛÙË Û˘¯Ó‹ ¯Ú‹ÛË ÙÔ˘˜ ·fi Ù· ËÏÈÎȈ̤ӷ ¿ÙÔÌ· Ô˘ Û˘¯Ó¿ ÊÚÔÓÙ›˙Ô˘Ó Ù· ·È‰È¿, ·ÏÏ¿ Î·È ÛÙË Ï·Óı·Ṳ̂ÓË ÙÔÔı¤ÙËÛ‹ ÙÔ˘˜ ·fi ÙÔ˘˜ ÁÔÓ›˜ Û ÚÔÛÂÁÁ›ÛÈÌ· ÁÈ· ÙÔ ·È‰› ÛËÌ›· ÙÔ˘ ÛÈÙÈÔ‡. ∫Ô˘˙›Ó· (Ô ÈÔ ÂÈΛӉ˘ÓÔ˜ ¯ÒÚÔ˜ ÙÔ˘ ÛÈÙÈÔ‡) ∆· ÈÔ Û˘¯Ó¿ ·È‰Èο ·Ù˘¯‹Ì·Ù· ·ÊÔÚÔ‡Ó Û ÂÁη‡Ì·Ù· ·fi ˙ÂÛÙfi ÓÂÚfi ÁÈ· Ì·Á›ÚÂÌ·, χÛÈÌÔ Î·È ·Ú·Û΢‹ ·Ê„ËÌ¿ÙˆÓ, ηıÒ˜ Î·È ·fi Â·Ê‹ Ì ÌÂÙ·ÏÏÈΤ˜ ÂÛٛ˜ Ù˘ ÎÔ˘˙›Ó·˜ ‹ ËÏÂÎÙÚÈο Û›‰ÂÚ·. ¶·Ú¿ÁÔÓÙ˜ Èı·ÓÔ‡ ÎÈÓ‰‡ÓÔ˘ Â›Ó·È Â›Û˘: ·) ÙÔ Î·˘Ùfi Ê·ÁËÙfi-ÓÂÚfi Û ̷ÁÂÈÚÈο Û·Ë, ‚) ÔÈ ‚Ú·ÛÙ‹Ú˜ ÓÂÚÔ‡, Á) ÔÈ ËÏÂÎÙÚÈΤ˜ Û˘Û΢¤˜, ‰) ÔÈ ‰È·ÎfiÙ˜ ÎÔ˘˙›Ó·˜ (ȉȷ›ÙÂÚ· ·Ó Â›Ó·È ·Î¿Ï˘ÙÔÈ) Î·È Â) Ù· ÔχÚÈ˙· Î·È Ù· ÂÎÙÂıÂÈ̤ӷ ηÏ҉ȷ (28). √È ËÏÂÎÙÚÈÎÔ› Ù·¯˘‚Ú·ÛÙ‹Ú˜ (ÔÈ ÔÔ›ÔÈ ·ÓÙÈη٤ÛÙËÛ·Ó ÙÔÓ ·Ï·ÈfiÙÂÚÔ ÙÚfiÔ ı¤Ú¶·È‰È·ÙÚÈ΋ 2006;69:268-277

Ì·ÓÛ˘ ÙÔ˘ ÓÂÚÔ‡) ·ÔÙÂÏÔ‡Ó Û˘¯Ó‹ ·ÈÙ›· ÂÁη˘Ì¿ÙˆÓ ÁÈ· Ù· ·È‰È¿ (29), fiˆ˜ Î·È ÔÈ fiÚÙ˜ ÙÔ˘ ËÏÂÎÙÚÈÎÔ‡ ÊÔ‡ÚÓÔ˘ (30). ∞Ù˘¯‹Ì·Ù· ÛÙÔ ÏÔ˘ÙÚfi-Ì¿ÓÈÔ ¶ÚfiÛÊ·Ù· ÛÙËÓ ∂ÏÏ¿‰·, Ù· ªª∂ ·Û¯ÔÏ‹ıËÎ·Ó ¤ÓÙÔÓ· Ì ÙËÓ ÂÚ›ÙˆÛË ‚Ú¤ÊÔ˘˜ Ô˘ ¿ÓÔÈÍ ÙË ‚Ú‡ÛË ÙÔ˘ ˙ÂÛÙÔ‡ ÓÂÚÔ‡ (ÛÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô˘ Ë ‚ÚÂÊÔÎfiÌÔ˜ ÙÔ ¿ÊËÛ ÌfiÓÔ ÙÔ˘ ÁÈ· Ó· ÌÂÙ·‚› ÁÈ· ÙÔÓ ÚÔ˘¯ÈÛÌfi ÙÔ˘). ∆· ÂÁη‡Ì·Ù· ÛÙÔ Ì¿ÓÈÔ ·ÔÙÂÏÔ‡Ó Û˘¯Ófi ·ÔÙ¤ÏÂÛÌ· ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ Î·È ÔÊ›ÏÔÓÙ·È Î˘Ú›ˆ˜ ÛÙËÓ ·ÚÔÛÂÍ›· Î·È ÛÙËÓ ¤ÏÏÂÈ„Ë ÚÔÓÔËÙÈÎfiÙËÙ·˜ ÙˆÓ ÂÓËÏ›ÎˆÓ ÁÈ· ÙÔ˘˜ ÎÈÓ‰‡ÓÔ˘˜ Ô˘ ÂÏÏÔ¯Â‡Ô˘Ó ÛÙÔÓ ¯ÒÚÔ ·˘Ùfi (31). π‰È·›ÙÂÚ· ÂÈΛӉ˘ÓÔÈ (·ÏÏ¿ fi¯È ·ÎfiÌ· ‰È·‰Â‰Ô̤ÓÔÈ ÛÙËÓ ∂ÏÏ¿‰·) Â›Ó·È ÔÈ ‚Ú·ÛÙ‹Ú˜ ÓÂÚÔ‡ (ıÂÚÌÔۛʈÓ˜) Ô˘ ÏÂÈÙÔ˘ÚÁÔ‡Ó Ì ·¤ÚÈÔ, ηıÒ˜ Ë ‰È·Ê˘Á‹ ÌÔÓÔÍÂȉ›Ô˘ ÙÔ˘ ¿Óıڷη (CO) ηٿ ÙË ‰È¿ÚÎÂÈ· ÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ Û˘Û΢‹˜ ¤¯ÂÈ ÂÓÔ¯ÔÔÈËı› ÁÈ· ·ÚÎÂÙ¿ ı·Ó·ÙËÊfiÚ· ÂÚÈÛÙ·ÙÈο ‰ÈÂıÓÒ˜ (32). ™Â ÌÂϤÙË Ù˘ Consumer Product Safety Commission (33) ÙˆÓ ∏¶∞, Ô˘ η٤ÁÚ·„ ÙÔ˘˜ ‚ÚÂÊÈÎÔ‡˜ ı·Ó¿ÙÔ˘˜ ·fi ÓÈÁÌfi (ηٿ ÙËÓ ÂÚ›Ô‰Ô 1983-1995), ÛËÌÂÈÒÓÔÓÙ·È Ù· ÂÍ‹˜: ·) ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ı¿Ó·ÙÔÈ (84%) ÛËÌÂÈÒıËÎ·Ó Û ·È‰È¿ ËÏÈΛ·˜ 5-15 ÌËÓÒÓ Ì ̤ÛË ËÏÈΛ· ÙÔ˘˜ 8 Ì‹Ó˜, ‚) ÙÔ 90% ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ·Ô‰fiıËΠ۠ÂÏÏÈ‹ Â›‚ÏÂ„Ë ·fi ÙÔ˘˜ ÁÔÓ›˜ (Ì ̤ÛÔ ¯ÚfiÓÔ ·Ô˘Û›·˜ Ù· 6 ÏÂÙ¿) Î·È Á) ·ÚÎÂÙÔ› ·fi ÙÔ˘˜ ÁÔÓ›˜ (‹ ÙȘ babysitters) ¯ÚËÛÈÌÔÔÈÔ‡Û·Ó ÁÈ· ÙË ‰È¢ÎfiÏ˘ÓÛ‹ ÙÔ˘˜ ÂȉÈο ·È‰Èο ηı›ÛÌ·Ù· Ì¿ÓÈÔ˘. ¶ÙÒÛÂȘ (Ì·ÏÎfiÓÈ·, Ù·Ú¿ÙÛ˜, Îϛ̷Θ) ∏ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÙÒÛÂˆÓ ·˘Ù‹˜ Ù˘ ηÙËÁÔÚ›·˜ Û˘Ì‚·›ÓÂÈ ÂÍ·ÈÙ›·˜ Ù˘ Û˘Ó‹ıÂÈ·˜ ÙˆÓ ·ÓıÚÒˆÓ Ó· οıÔÓÙ·È ‹ Ó· ÎÔÈÌÔ‡ÓÙ·È

273

¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ

ÂΛ ηٿ ÙÔ˘˜ ˙ÂÛÙÔ‡˜ Ì‹Ó˜ ÙÔ˘ ¤ÙÔ˘˜, ¯ˆÚ›˜ Ó· ·ÓÙÈÏ·Ì‚¿ÓÔÓÙ·È ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· Ù· ·È‰È¿. ∞fi ¤Ú¢ӷ Ô˘ ‰ÈÂÍ‹¯ıË ÛÙËÓ ∆Ô˘ÚΛ· (34), ‚Ú¤ıËΠfiÙÈ ÙÔ 54,5% fiÏˆÓ ÙˆÓ ÙÒÛÂˆÓ Û˘Ì‚·›ÓÂÈ Î·Ù¿ ÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÌÂٷ͇ ª·˝Ô˘-∞˘ÁÔ‡ÛÙÔ˘. ∆· ÎÈÁÎÏȉÒÌ·Ù· ÛÙȘ ‚ÂÚ¿ÓÙ˜ Î·È ÛÙȘ Ù·Ú¿ÙÛ˜ Û˘Ó‹ıˆ˜ ‰ÂÓ ÙËÚÔ‡Ó ÙȘ ηıÔÚÈṲ̂Ó˜ ÚԉȷÁڷʤ˜ ·ÛÊ·Ï›·˜ (ÛˆÛÙfi ‡„Ô˜), ηıÒ˜ Â›Ó·È Û¯Â‰È·Ṳ̂ӷ ‚¿ÛÂÈ ·ÈÛıËÙÈÎÒÓ ÎÚÈÙËÚ›ˆÓ. ∆Ú›· Â›Ó·È Ù· ‚·ÛÈο ÛËÌ›· ÚfiÎÏËÛ˘ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ÛÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜: ·) Ù· ¯·ÌËÏ¿ οÁÎÂÏ· ÙˆÓ Ì·ÏÎÔÓÈÒÓ, Ù· ÔÔ›· ›Ù ‰ÂÓ Â›Ó·È ÛÙ·ıÂÚ¿ ηٷÛ΢·Ṳ̂ӷ, ›Ù ‰È·ı¤ÙÔ˘Ó ÌÂÁ¿Ï· ‰È¿ÎÂÓ·, ‚) Ë ‰˘Ó·ÙfiÙËÙ· ÂχıÂÚ˘ ÚfiÛ‚·Û˘ ÙˆÓ ·È‰ÈÒÓ ÚÔ˜ ÙËÓ Ù·Ú¿ÙÛ· (ȉȷ›ÙÂÚ· ηٿ ÙÔ ‰È¿ÛÙËÌ· Ô˘ Ô ÁÔÓ¤·˜ ‹ Ô ÂȂϤˆÓ Â›Ó·È ··Û¯ÔÏË̤ÓÔ˜) Î·È Á) ÔÈ ÌÂÁ¿Ï˜ ÂÈÊ¿ÓÂȘ Ù˙·ÌÈÒÓ Ô˘ ‰ÂÓ ‰È¢ÎÔχÓÔ˘Ó ÙË ‰˘Ó·ÙfiÙËÙ· ‰È¿ÎÚÈÛ˘-·ÓÙ›Ï˄˘ ÙÔ˘ Á˘¿ÏÈÓÔ˘ ¯ˆÚ›ÛÌ·ÙÔ˜ (35). ÃÚ‹ÛË ·ÓÂÏ΢ÛÙ‹ÚˆÓ ªÔÚ› Ë Û¯ÂÙÈ΋ ÈӷΛ‰· Ó· ·ÔÙÚ¤ÂÈ ÙË ¯Ú‹ÛË ·ÓÂÏ΢ÛÙ‹ÚˆÓ Û ·È‰È¿ ËÏÈΛ·˜ οو ÙˆÓ 14 ÂÙÒÓ, ·˘Ùfi fï˜ Û¿ÓÈ· ÌÔÚ› Ó· ÂÊ·ÚÌÔÛÙ› ÛÙËÓ Ú¿ÍË. ∆· ·È‰Èο ·Ù˘¯‹Ì·Ù· ·fi Ï·Óı·Ṳ̂ÓË ¯Ú‹ÛË ·ÓÂÏ΢ÛÙ‹Ú· ÂÚÈÏ·Ì‚¿ÓÔ˘Ó: ·) ··Á¯ÔÓÈÛÌÔ‡˜, ‚) ÛÔ‚·Úfiٷ٘ ηÎÒÛÂȘ Î·È Á) ËÏÂÎÙÚÔÏËÍ›·. ∂Áη‡Ì·Ù· ∏ ÓËȷ΋ ËÏÈΛ· Â›Ó·È Ë ϤÔÓ ÂÈÚÚÂ‹˜ Û ÂÁη‡Ì·Ù·. ™Ù· Ôχ ÌÈÎÚ¿ ·È‰È¿ (1-2 ÂÙÒÓ) ·ÈÙ›· ÙÔ˘ ÂÁη‡Ì·ÙÔ˜ Â›Ó·È Û˘Ó‹ıˆ˜ Ë ·Ó·ÙÚÔ‹ ‰Ô¯Â›Ô˘ Ì ˙ÂÛÙfi ÓÂÚfi ÛÙËÓ ÂÛÙ›· Ù˘ ÎÔ˘˙›Ó·˜ ‹ ÛÙÔ ÙÚ·¤˙È, ÂÓÒ ÛÙ· ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ Û˘¯Ó‹ Ë Û‡ÁÎÚÔ˘Û‹ ÙÔ˘˜ Ì ÂÓ‹ÏÈΘ Ô˘ ÎÚ·ÙÔ‡Ó ‰Ô¯Â›Ô Ì ˙ÂÛÙfi ÓÂÚfi ‹ Ê·ÁËÙfi (36). ™Ô‚·Ú¿ ÂÁη‡Ì·Ù· ÌÔÚ› Ó· ÚÔÎÏËıÔ‡Ó Î·È fiÙ·Ó ÙÔ ·È‰› ÂÈÚ·Ì·Ù›˙ÂÙ·È Ì Û›ÚÙ· Î·È ÔÈÓfiÓÂ˘Ì·. ™˘¯ÓfiÙÂÚ· Â›Ó·È Ù· ÂÁη‡Ì·Ù· ÛÙ· ·È‰È¿ Ô˘ ˙Ô˘Ó Û ‰È·ÌÂÚ›ÛÌ·Ù· ÔÏ˘Î·ÙÔÈÎÈÒÓ, ÂÓÒ fiÛÔÓ ·ÊÔÚ¿ ÛÙÔ Ê‡ÏÔ, Ë Û˘¯ÓfiÙËÙ· ÛÙ· ·ÁfiÚÈ· Â›Ó·È ‰‡Ô ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚË Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ·. ™ËÌ·ÓÙÈÎfi ΛӉ˘ÓÔ ·ÔÙÂÏ› Î·È ÙÔ ËÏÂÎÙÚÈÎfi Û›‰ÂÚÔ, ȉȷ›ÙÂÚ· ÁÈ· Ù· ·ÁfiÚÈ· ËÏÈΛ·˜ 1-2 ÂÙÒÓ (37). ∂ÎÙfi˜ ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ô˘ ÚԷӷʤÚıËηÓ, ·Í›˙ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÌÈÎÚfi ÔÛÔÛÙfi ÙˆÓ ÂÁη˘Ì¿ÙˆÓ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ Ê·›ÓÂÙ·È Ó· ÚÔ¤Ú¯ÂÙ·È ·fi οÔÈÔ˘ ›‰Ô˘˜ ηÎÔÔ›Ë-

ÛË. ø˜ ·Ú¿‰ÂÈÁÌ· ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ë ÂÚ›ÙˆÛË ÂÓfi˜ ÎÔÚÈÙÛÈÔ‡ ËÏÈΛ·˜ 2ó ÂÙÒÓ, ÁÈ· ÙÔ ÔÔ›Ô ˘‹Ú¯Â Ë ˘Ô„›· ۈ̷ÙÈ΋˜ ηÎÔÔ›ËÛ˘. ∏ ÎÏÈÓÈ΋ ÂͤٷÛË Î·È Ë ÌÂÙ¤ÂÈÙ· ¤Ú¢ӷ ·ÔÎ¿Ï˘„·Ó ‚’ ‚·ıÌÔ‡ ÂÁη‡Ì·Ù· Î·È ÛÙȘ ‰‡Ô Ï¢ڤ˜, Ô˘ ÚÔÎÏ‹ıËÎ·Ó ·fi ÙÔÓ Û‡ÓÙÚÔÊÔ Ù˘ ÌËÙ¤Ú·˜ ̤ۈ Ù˘ ›ÂÛ˘ ÂÓfi˜ ¯ÂÈÚÔΛÓËÙÔ˘ ÛÙÂÁÓˆÙ‹Ú· Ì·ÏÏÈÒÓ ¿Óˆ ÛÙÔ ‰¤ÚÌ· ÙÔ˘ ·È‰ÈÔ‡ (38). ∂›Û˘, ȉȷ›ÙÂÚ· ÂÈΛӉ˘Ó˜ Â›Ó·È Î·È ÔÈ ¿Ó˜ ÙÔ˘ ̈ÚÔ‡, ÔÈ Ôԛ˜ Û‡Ìʈӷ Ì ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ·Ô‰Âȯı› ÂÍ·ÈÚÂÙÈο ‡ÊÏÂÎÙ˜ (39). ÕÏϘ ÌÔÚʤ˜ ·Ù˘¯ËÌ¿ÙˆÓ ∏ ËÏÂÎÙÚÔÏËÍ›· ·fi Ú‡̷ ¯·ÌËÏ‹˜ Ù¿Ûˆ˜ ·ÔÙÂÏ› Û˘¯Ófi ·È‰ÈÎfi ·Ù‡¯ËÌ· Ô˘ ‰‡Ó·Ù·È Ó· ÚÔηϤÛÂÈ ÙÂÙ·Ó›·, ηډȷΤ˜ ‰È·Ù·Ú·¯¤˜ Î·È ‰Â˘ÙÂÚ‡ԢÛ˜ ‚Ï¿‚˜, ·ÎfiÌ· (Ê˘ÛÈο) Î·È ÙÔÓ ı¿Ó·ÙÔ (40). ∏ ÂÈÛÚfiÊËÛË Î·˘ÛÙÈÎÒÓ Ô˘ÛÈÒÓ Ô‰ËÁ› Û ÔÈÛÔÊ·ÁÈ΋ ÛÙ¤ÓˆÛË (41). ∞ÚÎÂÙ¿ ÂÚÈÛÙ·ÙÈο ÔÊ›ÏÔÓÙ·È Î·È Û ηٿÔÛË ËÏÂÎÙÚÈÎÒÓ Ì·Ù·ÚÈÒÓ, ÁÂÁÔÓfi˜ Ô˘ ÚÔηÏ› Î·È ÂÁη‡Ì·Ù· ÂÍ·ÈÙ›·˜ ÙˆÓ ˘ÁÚÒÓ Ô˘ ‰È·ÚÚ¤Ô˘Ó ÛÙÔ˘˜ Á‡Úˆ Ì·Ï·ÎÔ‡˜ ÈÛÙÔ‡˜ (42). ™Â ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ Û˘ÓÈÛÙ¿Ù·È ÚÒÈÌÔ˜ ÂÓ‰ÔÛÎÔÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÚÔÎÂÈ̤ÓÔ˘ Ó· ηıÔÚÈÛÙ› Ë ÛÔ‚·ÚfiÙËÙ· Ù˘ ‚Ï¿‚˘. øÛÙfiÛÔ, Â¿Ó ÙÔ ·È‰› Â›Ó·È ·Û˘Ìو̷ÙÈÎfi, ı· ‹Ù·Ó ÈÔ ·ÛʷϤ˜ Ó· ·ÔÊ¢¯ı› Ô ÂÓ‰ÔÛÎÔÈÎfi˜ ¤ÏÂÁ¯Ô˜, ÚÔÎÂÈ̤ÓÔ˘ Ó· ÌËÓ ÚÔÎÏËıÔ‡Ó ÂÚ·ÈÙ¤Úˆ ÚÔ‚Ï‹Ì·Ù· (43). ™ÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ Â›Ó·È Èı·Ófi Ó· ·Ú·ÙËÚËıÔ‡Ó ÙÒÛÂȘ ÙÔ˘ ·È‰ÈÔ‡ ·fi ÙÔ ÎÚ‚¿ÙÈ, ÙËÓ ÎÔ˘Î¤Ù· (44) ‹ ·fi „ËϤ˜ ηڤÎϘ (45). ∏ ¯ÂÈÚÔΛÓËÙË ÎÔ‡ÓÈ· ¤¯ÂÈ ÂÓÔ¯ÔÔÈËı› ÁÈ· ÙËÓ ÚfiÎÏËÛË .¯. ·ÚÎÂÙÒÓ Î·Ù·ÁÌ¿ÙˆÓ, ÂÓÒ ÛÙ· ·Ù˘¯‹Ì·Ù· Ô˘ ÂÓ¤¯Ô˘Ó ÙÒÛÂȘ ·fi ηڤÎϘ, Ù· ̈ڿ ÚÔÛ·ıÔ‡Ó Ó· ÛËΈıÔ‡Ó ¯ˆÚ›˜ ÙÔ Î¿ıÈÛÌ· Ó· ¤¯ÂÈ ÂÚȉÂı› ‹ Ó· ¤¯Ô˘Ó ÏËÊı› ÚÔÏËÙÈο ̤ÙÚ· ÁÈ· ÙË ÛÙ·ıÂÚfiÙËÙ· Ù˘ ηڤÎÏ·˜ (46). ™ÙË ¯ÒÚ· Ì·˜, Û˘Ì‚·›ÓÔ˘Ó Û˘ÓÔÏÈο ÂÚ›Ô˘ 4.400 ÙÚ·˘Ì·ÙÈÛÌÔ› ·È‰ÈÒÓ ·fi ÙÒÛÂȘ Û ÂÙ‹ÛÈ· ‚¿ÛË (47). ∂Í ·˘ÙÒÓ, ÔÛÔÛÙfi 10% ÂÚ›Ô˘ ··ÈÙ› ÓÔÛËÏ›· (47). ∞Í›˙ÂÈ, Â›Û˘, Ó· ÛËÌÂȈı› Ô Û˘Ó¯Ҙ ·˘Í·ÓfiÌÂÓÔ˜ ·ÚÈıÌfi˜ ÙˆÓ ·È‰È·ÙÚÈÎÒÓ ÙÚ·˘Ì¿ÙˆÓ ÛÙÔ ÎÂÊ¿ÏÈ ÂÍ·ÈÙ›·˜ Ù˘ ÙÒÛ˘ Ù˘ Û˘Û΢‹˜ Ù˘ ÙËÏÂÔÚ¿Ûˆ˜, ÛÂ Û˘Ó¿ÚÙËÛË Ì ÙËÓ ·‡ÍËÛË ÙˆÓ ˆÏ‹ÛÂÒÓ ÙÔ˘˜ ·Ó¿ ÔÈÎÔÁ¤ÓÂÈ·. ™Ù·ÙÈÛÙÈΤ˜ ¤Ú¢Ó˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Ë ÏÂÈÔÓfiÙËÙ· ·˘ÙÔ‡ ÙÔ˘ ›‰Ô˘˜ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ¶·È‰È·ÙÚÈ΋ 2006;69:268-277

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∫. ∫·ÏÔ‹Ù· Î·È Û˘Ó.

Û˘Ì‚·›ÓÂÈ Û ·È‰È¿ ËÏÈΛ·˜ 1-3 ÂÙÒÓ, Ù· ÔÔ›· ·Ú¤ÌÂÈÓ·Ó ÛÙÔ Û›ÙÈ ¯ˆÚ›˜ Â›‚Ï„Ë. ∆Ô ÔÛÔÛÙfi ıÓËÛÈÌfiÙËÙ·˜ ‹Ù·Ó ȉȷ›ÙÂÚ· ˘„ËÏfi, ÂȉÈο ÛÙ· ·È‰È¿ Ì Â·ÎfiÏÔ˘ıÔ ÙÚ·‡Ì· ÛÙÔ ÎÂÊ¿ÏÈ (48,49). ™ÙȘ ·ÓÒÙÂÚ˜ ÔÈÎÔÓÔÌÈο Ù¿ÍÂȘ ·Ú·ÙËÚÂ›Ù·È ÙÔ Ê·ÈÓfiÌÂÓÔ ÙÔ˘ ÓÈÁÌÔ‡ ‹ ÙÔ˘ ‰Â˘ÙÂÚÔ·ıÔ‡˜ ÓÈÁÌÔ‡ Û ÈÛ›Ó·, Û˘¯ÓfiÙÂÚ· ı‡Ì·Ù· ÙˆÓ ÔÔ›ˆÓ Â›Ó·È Ù· ·È‰È¿ ËÏÈΛ·˜ 1-4 ÂÙÒÓ Î·È ÂȉÈο Ù· ·ÁfiÚÈ· ‹ Ù· ·È‰È¿ Ô˘ ¿Û¯Ô˘Ó ·fi ÂÈÏË„›·. ∆Ô 46% ·˘ÙÒÓ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Û˘Ó¤‚Ë Î·Ù¿ ÙÔ˘˜ ¯ÂÈÌÂÚÈÓÔ‡˜ Ì‹Ó˜, ÂÓÒ Ù· ÌÈÛ¿ ·fi ·˘Ù¿ ÔÊ›ÏÔÓÙ·Ó Û ¤ÏÏÂÈ„Ë Î¿ÔÈÔ˘ ̤ÛÔ˘ ÚÔÛÙ·Û›·˜ (.¯. ÚÔÛٷ٢ÙÈÎfi ‰›¯Ù˘) (50). ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ·È¯ÓȉÈÔ‡ ÂÓ‰¤¯ÂÙ·È Ó· ÚÔÎÏËıÔ‡Ó ÙÚ·˘Ì·ÙÈÛÌÔ› ÙˆÓ ÔÊı·ÏÌÒÓ Î·È ÙˆÓ ·˘ÙÈÒÓ. Œ¯ÂÈ ‚ÚÂı› fiÙÈ ‰È·ÂÚ·ÛÙÈο ÙÚ·‡Ì·Ù· ÙÔ˘ ÔÊı·ÏÌÔ‡ Û˘Ì‚·›ÓÔ˘Ó Î˘Ú›ˆ˜ ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ ÏfiÁˆ ·È¯ÌËÚÒÓ ÂÚÁ·Ï›ˆÓ ‹ ·ÓÙÈÎÂÈÌ¤ÓˆÓ Ô˘ ‚Ú›ÛÎÔÓÙ·È Ù˘¯·›· ÛÙÔ ¿ÙˆÌ· (51). ∂Í›ÛÔ˘ ÂÈΛӉ˘Ó· Â›Ó·È Î·È Ù· baby-walkers (·È‰ÈΤ˜ “ÛÙÚ¿Ù˜”), ÂÓÒ ¤¯Ô˘Ó ÛËÌÂȈı› ·ÚÎÂÙ¿ ·Ù˘¯‹Ì·Ù· Ì ÙÔ˘˜ ÈÌ¿ÓÙ˜ ÙˆÓ ÔÚÁ¿ÓˆÓ Á˘ÌÓ·ÛÙÈ΋˜ Ô˘ ‚Ú›ÛÎÔÓÙ·È Ì¤Û· ÛÙÔ Û›ÙÈ (52). ∂ÈϤÔÓ, Â›Ó·È ·˘ÙÔÓfiËÙÔ fiÙÈ Ë ·ÛÊ·Ï‹˜ ·Ôı‹Î¢ÛË Î·È Ê‡Ï·ÍË ÙˆÓ fiÏˆÓ Û ¿ÁÓˆÛÙ· Î·È Ï›·Ó ‰˘ÛÚfiÛÈÙ· ÁÈ· ÙÔ ·È‰› ̤ÚË, ·ÔÙÂÏ› ··Ú·›ÙËÙË ÚÔ¸fiıÂÛË ÔÏÔηÙÔ¯‹˜ ÔÔÈÔ˘‰‹ÔÙ ÁÔÓ¤· (53). ™ÙÔ Ï·›ÛÈÔ Ì›·˜ ·ÁÚÔÙÈ΋˜ ‹ ÚÔ·ÛÙȷ΋˜ ηÙÔÈΛ·˜, ÔÈ Î›Ó‰˘ÓÔÈ ÁÈ· ÙÔ ·È‰› ·˘Í¿ÓÔÓÙ·È. ¶·Ú·ÙËÚÔ‡ÓÙ·È ÂÚÈÛÛfiÙÂÚ· ÎÚÔ‡ÛÌ·Ù· ‰ËÏËÙËÚ›·Û˘ ·fi ÁˆÚÁÈο Ê¿Ú̷η (54), ÙÒÛÂȘ ·fi ÛοϘ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û˘¯Ó¿ (55), ÙÚ·‡Ì·Ù· ·fi Ì˯·Ó¤˜ ÂÚÈÔ›ËÛ˘ ÁÚ·ÛȉÈÔ‡ (56), ·ÎfiÌË Î·È ·fi ÌË ÂÏÂÁ¯fiÌÂÓË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ȉȈÙÈÎÔ‡ ¯ÒÚÔ˘ ÛÙ¿ıÌ¢Û˘. ™ÙËÓ ∂ÏÏ¿‰·, ηٷÁÚ¿ÊËÎ·Ó Û˘ÓÔÏÈο 4.326 ·Ù˘¯‹Ì·Ù· Û ·ÁÚÔÙÈÎfi ÂÚÈ‚¿ÏÏÔÓ Î·Ù¿ ÙËÓ ÂÓÙ·ÂÙ›· 1996-2000, ÂÎ ÙˆÓ ÔÔ›ˆÓ Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ·ÊÔÚÔ‡Û Û η΋ ¯Ú‹ÛË ÙˆÓ ÁˆÚÁÈÎÒÓ Ô¯ËÌ¿ÙˆÓ (57). π‰È·›ÙÂÚË ÛËÌ·Û›· ÁÈ· ÙËÓ ¤Î‚·ÛË ÂÓfi˜ ·Ù˘¯‹Ì·ÙÔ˜ ¤¯ÂÈ Ë Û˘ÌÂÚÈÊÔÚ¿ Î·È Ë ·ÓÙ›‰Ú·ÛË ÙˆÓ ÁÔÓ¤ˆÓ. ∞Í›˙ÂÈ Ó· ·Ó·ÊÂÚıԇ̠ÛÙË ÛÔÊ‹ ·ÓÙ›‰Ú·ÛË Ù˘ ÌËÙ¤Ú·˜ ÂÓfi˜ ·È‰ÈÔ‡ Ô˘ ·fi ·Ù‡¯ËÌ· ηÚÊÒıËΠ¤Ó· ÌÔχ‚È ÛÙËÓ Î·Ú‰È¿ ÙÔ˘. ∆Ô ·È‰› ηٿÊÂÚ ӷ ÂÈ˙‹ÛÂÈ ÁÈ·Ù› Ë ÌËÙ¤Ú· ÙÔ˘ ‰ÂÓ ÚÔÛ¿ıËÛ ӷ ÙÔ ÙÚ·‚‹ÍÂÈ, ·ÏÏ¿ ·Ï¿ ÙÔ ÌÂÙ¤ÊÂÚ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô (58). ¶·È‰È·ÙÚÈ΋ 2006;69:268-277

¶ÚfiÏË„Ë ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ÔÈÎÈ·ÎÔ‡ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ ∏ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Ì›˙ÔÓÔ˜ ÚÔ‚Ï‹Ì·ÙÔ˜ ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ Û˘ÓÔ„›˙ÂÙ·È ÛÙËÓ ÚÔÛ¿ıÂÈ· ÁÈ· ÙËÓ ÚfiÏË„‹ ÙÔ˘˜. ∏ ÚfiÏË„Ë Û˘Ó›ÛÙ·Ù·È ÛÙËÓ ÂÈÙ˘¯‹ ‰È·ÌfiÚʈÛË Î·È ÂÊ·ÚÌÔÁ‹: ·) ÔÚÁ¿ÓˆÛ˘ Î·È ÓÔÌÔıÂÙÈÎÒÓ Ì¤ÙÚˆÓ, ‚) ¤Ú¢ӷ˜ Î·È Á) ÂÎ·›‰Â˘Û˘. ¶¿Óˆ ·fi fiÏ·, ˆÛÙfiÛÔ, Ë ÚfiÏË„Ë ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ·ÏÏ·Á‹ ÓÔÔÙÚÔ›·˜ (22). ∏ ‰È·ÌfiÚʈÛË ÂÓÈ·›·˜ ÂıÓÈ΋˜ ÔÏÈÙÈ΋˜ ÛÙÔÓ ÙÔ̤· Ù˘ ÚfiÏ˄˘ ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ, Ë ‡·ÚÍË Û˘ÓÙÔÓÈÛÙÈÎÔ‡ ÊÔÚ¤· Î·È Ë ÓÔÌÔıÂÙÈ΋ Ï·ÈÛ›ˆÛË Ù˘ ‰ÈÂÚ‡ÓËÛ˘ οı ·È‰ÈÎÔ‡ ·Ù˘¯‹Ì·ÙÔ˜ Â›Ó·È ÙÔ ÚÒÙÔ ‚‹Ì· ÚÔ˜ ·˘Ù‹ ÙËÓ Î·Ù‡ı˘ÓÛË. ∏ ÂÊ·ÚÌÔÁ‹ ÚÔÁÚ·ÌÌ¿ÙˆÓ (Ì ‚¿ÛË Ù· ÂÏÏËÓÈο ̤ÙÚ· Î·È ‰Â‰Ô̤ӷ) ¤Ú¢ӷ˜ Î·È ‰ÈÂÚ‡ÓËÛ˘, ÙfiÛÔ ÙˆÓ ·ÈÙÈÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÚfiÎÏËÛ˘ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ fiÛÔ Î·È Ù˘ ÂÊ·ÚÌÔÁ‹˜ Ù˘ Û¯ÂÙÈ΋˜ ÓÔÌÔıÂÛ›·˜, ı· ʤÚÂÈ ÛÙÔ Êˆ˜ ÔÏÏ¿ ÛÙÔȯ›· Û¯ÂÙÈο Ì ÙÔ˘˜ ÂοÛÙÔÙ ÂÌÏÂÎfiÌÂÓÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, ÙËÓ ÂÈÎÈÓ‰˘ÓfiÙËÙ· ÙˆÓ ÂÈÎÚ·ÙÔ‡ÓÙˆÓ ¯ˆÚÔÙ·ÍÈÎÒÓ ÚԉȷÁÚ·ÊÒÓ, ·ÏÏ¿ Î·È ÙË ÓÔÛÔÎÔÌÂȷ΋ ÓÔÛËÏ›· Î·È ÙÔ ÎfiÛÙÔ˜ Û ¤Ì„˘¯Ô Î·È ÌË ˘ÏÈÎfi. ∆¤ÏÔ˜, Ë ÂÎ·›‰Â˘ÛË ı· Ú¤ÂÈ Ó· ÂÈÎÂÓÙÚˆı› ÛÙËÓ ÂÎfiÓËÛË Î·È ÂÊ·ÚÌÔÁ‹ ÚÔÁÚ·ÌÌ¿ÙˆÓ ˘Á›·˜ Ô˘ ı· ÚÔ‚¿ÏÏÔ˘Ó ÙË ÛËÌ·Û›· Ù˘ ÚfiÏ˄˘ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ, ÙÔÓ›˙ÔÓÙ·˜ ÙËÓ ·Ó·ÁηÈfiÙËÙ· ÂÎ·›‰Â˘Û˘ ÙÔ˘ ÁÔÓ¤·, ÙÔ˘ ‰·ÛοÏÔ˘, ·ÏÏ¿ Î·È ÙÔ˘ ›‰ÈÔ˘ ÙÔ˘ ·È‰ÈÔ‡. ∞fi ÏÂ˘Ú¿˜ ÁÔÓ¤ˆÓ Â›Ó·È ·Ó·Áη›· Ë ÂÈÌfiÚʈÛË Î·È Ë ·Ú·ÎÔÏÔ‡ıËÛË ÂȉÈÎÒÓ ÚÔÁÚ·ÌÌ¿ÙˆÓ, ¯ˆÚ›˜ ˆÛÙfiÛÔ Ó· ˘ÂÚÙÔÓ›˙ÂÙ·È Ë ·Ó¿ÁÎË ÁÈ· Û˘Ó¯‹ Â›‚ÏÂ„Ë Û ‚·ıÌfi Ô˘ Ó· ÂÚÈÔÚ›˙ÂÈ ÙËÓ ·ÓÂÍ·ÚÙËÛ›· ÙÔ˘ ·È‰ÈÔ‡ (59). ∏ Û˘ÌÂÚÈÊÔÚ¿ ÙˆÓ ÁÔÓ¤ˆÓ ÔÊ›ÏÂÈ Ó· ÚÔÛ·ÚÌfi˙ÂÙ·È ·Ó¿ÏÔÁ· Ì ÙËÓ ËÏÈΛ· ÙÔ˘ ·È‰ÈÔ‡, ηıÒ˜ ÔÈ Î›Ó‰˘ÓÔÈ - fiˆ˜ ÚԷӷʤÚıËΠ- ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û οı ÛÙ¿‰ÈÔ Ù˘ ˙ˆ‹˜ ÙÔ˘˜. ∏ ÂÎ·›‰Â˘ÛË ÙˆÓ ›‰ÈˆÓ ÙˆÓ ·È‰ÈÒÓ Â›Ó·È Â›Û˘ ÎÂÊ·Ï·ÈÒ‰Ô˘˜ ÛËÌ·Û›·˜, ηıÒ˜ Ë ÁÓÒÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÌÔÚ› Ó· ÙÔ ·ÔÙÚ¤„ÂÈ ·fi ÛËÌ·ÓÙÈο Ï¿ıË. ∞˘Ùfi ·ÔÎÙ¿ ȉȷ›ÙÂÚË ÛËÌ·Û›·, Â¿Ó ÔÈ ÁÔÓ›˜ ·ÓÙÈÏËÊıÔ‡Ó fiÙÈ Ë ÚÔÛˆÈÎfiÙËÙ· ‹ Ë „˘¯ÔÛ‡ÓıÂÛË ÙÔ˘ ·È‰ÈÔ‡ ÙÔ˘˜ ÙÔ Ô‰ËÁ› Û ȉȷ›ÙÂÚ· ÂÈΛӉ˘Ó˜ ÂÓ¤ÚÁÂȘ. º˘ÛÈο, Ë ÂÎ·›‰Â˘ÛË ÙˆÓ ·È‰ÈÒÓ ‰ÂÓ ¤¯ÂÈ Î·Ì›· ÛËÌ·Û›· fiÙ·Ó ÚfiÎÂÈÙ·È .¯. ÁÈ· ‚Ú¤ÊË (fiÔ˘ Ë Â›‚ÏÂ„Ë ÎÚ›ÓÂÙ·È ÂÈÙ·ÎÙÈ΋) (60). ∆· ÚÔÁÚ¿ÌÌ·Ù· ÙˆÓ ÂÈÛÎÂÙÒÓ ÀÁ›·˜

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¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ

ÛÙÔ ÔÈÎÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ (fiÔ˘ ·˘Ù¿, Ê˘ÛÈο, ÂÊ·ÚÌfiÛÙËηÓ) ¤¯Ô˘Ó ·Ô‰Âȯı› ȉȷÈÙ¤Úˆ˜ ·ÔÙÂÏÂÛÌ·ÙÈο ÛÙËÓ ·ÔÙÚÔ‹ ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ. ∂›Ó·È ÎÔÈÓ‹ ›ÛÙË ÙˆÓ ÂÚ¢ÓËÙÒÓ fiÙÈ Ù· ÚÔÁÚ¿ÌÌ·Ù· ·˘Ù¿ ÌÔÚÔ‡Ó Ó· Â›Ó·È È‰È·›ÙÂÚ· ˆÊ¤ÏÈÌ·, Û˘Ì‚¿ÏÏÔÓÙ·˜ ÛÙËÓ ·ÏÏ·Á‹ Ù˘ Û˘ÌÂÚÈÊÔÚ¿˜ ÙˆÓ ÂÓËÏ›ÎˆÓ (61,62). ™ËÌ·ÓÙÈÎfi ÛÙÔÈ¯Â›Ô ÁÈ· ÙËÓ ÚfiÏË„Ë ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ·ÔÙÂÏ› Ë ‡·ÚÍË Û˘Ó‰˘·ÛÌÔ‡ ÓfiÌˆÓ Î·È Î·ÓfiÓˆÓ, ÈηÓÒÓ Ó· ·Ó·ÚÔÛ·ÚÌfi˙ÔÓÙ·È ‰È·ÚÎÒ˜ ÛÙȘ ÌÂÙ·‚·ÏÏfiÌÂÓ˜ ‚ÈÔÙÈΤ˜ Û˘Óı‹Î˜. √Úıfi˜ Î·È ·ÛÊ·Ï‹˜ ·Ú¯ÈÙÂÎÙÔÓÈÎfi˜ ۯ‰ȷÛÌfi˜ ÛËÌ·›ÓÂÈ: ·) ·ÔÊ˘Á‹ ηٷÛ΢‹˜ ·fiÙÔÌˆÓ Î·È ¯ˆÚ›˜ ÎÔ˘·ÛÙ‹ ÎÏÈ̿ΈÓ, ‚) ‡·ÚÍË Î·Ù¿ÏÏËÏÔ˘ ʈÙÈÛÌÔ‡ ̤۷ Î·È Á‡Úˆ ·fi ÙÔ Û›ÙÈ, Á) ÔÚı‹ ηٷÛ΢‹ ÎÈÁÎÏȉˆÌ¿ÙˆÓ Û ‚ÂÚ¿ÓÙ˜ Î·È Ù·Ú¿ÙÛ˜ (‡„Ô˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ 105 cm Î·È ·ÔÌ¿ÎÚ˘ÓÛË ÔÚÈ˙fiÓÙÈˆÓ ‰È·Û˘Ó‰¤ÛÂˆÓ Û ¯·ÌËÏ¿ ‡„Ë), ‰) Î¿Ï˘„Ë Î¿ı ¯ÒÚÔ˘ Û˘ÏÏÔÁ‹˜ ‡‰·ÙÔ˜ (ËÁ¿‰È·, ÛÙ¤ÚÓ˜, ÈÛ›Ó˜), Â) ·ÔÎÏÂÈÛÌfi˜ Ù˘ ÚfiÛ‚·Û˘ ÚÔ˜ ÙËÓ Ù·Ú¿ÙÛ· (fi¯È fï˜ Ì ÏԢΤÙÔ, ηıÒ˜ Ú¤ÂÈ Ó· ÏÂÈÙÔ˘ÚÁ› Î·È ˆ˜ ‰›Ô‰Ô˜ ‰È·Ê˘Á‹˜ Û ÂÚ›ÙˆÛË ˘ÚηÁÈ¿˜), ÛÙ) ÙÔÔı¤ÙËÛË ·˘ÙfiÌ·ÙÔ˘ ‰È·ÎfiÙË ÛÙÔÓ ›Ó·Î· ÙÔ˘ ËÏÂÎÙÚÈÎÔ‡ ÁÈ· ÙËÓ ÚfiÏË„Ë ËÏÂÎÙÚÔÏËÍ›·˜ Î·È ˙) ‰˘Ó·ÙfiÙËÙ· Ù·ÎÙÈÎÔ‡ ÂϤÁ¯Ô˘ Ù˘ ‰È·Ê˘Á‹˜ ·ÂÚ›Ô˘. ŸÛÔÓ ·ÊÔÚ¿ Û ÈÔ Ú·ÎÙÈο-ηıËÌÂÚÈÓ¿ ˙ËÙ‹Ì·Ù·: ·) ÔÙ¤ ‰ÂÓ ÂÈÌË·ÓÔ˘Ì ÙÔ ÎÔÓÙfi ηÏÒ‰ÈÔ ÙÔ˘ Ù·¯˘‚Ú·ÛÙ‹Ú·, ¿ÓÙ· ÙÔÔıÂÙԇ̠ÙÔ Î·¿ÎÈ ÚÈÓ, ηٿ ÙË ‰È¿ÚÎÂÈ· Î·È ÌÂÙ¿ ÙË ¯Ú‹ÛË ÙÔ˘, ÂÓÒ ÙÔÔıÂÙԇ̠ÙÔÓ Ù·¯˘‚Ú·ÛÙ‹Ú· ηٿ ÚÔÙ›ÌËÛË Û „ËÏfi, ÌË-ÚÔÛ‚¿ÛÈÌÔ ÁÈ· Ù· ·È‰È¿ ÛËÌ›Ô, ‚) ‰ÂÓ ¯ÚËÛÈÌÔÔÈԇ̠ÛÙ· ÔχÚÈ˙· ÌÂÁ¿ÏÔ ·ÚÈıÌfi Û˘Û΢ÒÓ (ı¤ÚÌ·ÓÛË ÙÔ˘ ηψ‰›Ô˘, Èı·Ófi ‚Ú·¯˘Î‡Îψ̷), Á) ÂÈıˆÚԇ̠ٷ ηÏ҉ȷ (ȉȷ›ÙÂÚ· fiÛ· ‚Ú›ÛÎÔÓÙ·È ÛÙÔ ¿ÙˆÌ·) ÁÈ· ÛËÌ›· ÊıÔÚ¿˜ Î·È fiÙ·Ó ÎÚÈı› ·Ó·Áη›Ô Ù· ·ÏÏ¿˙Ô˘Ì (‰ÂÓ Ù· ÂȉÈÔÚıÒÓÔ˘ÌÂ), ‰) ‰›ÓÔ˘Ì ÌÂÁ¿ÏË ÚÔÛÔ¯‹ ÛÙË ıÂÚÌÔÎÚ·Û›· ÙÔ˘ ÓÂÚÔ‡ Ô˘ ı· ¯ÚËÛÈÌÔÔÈËı› ÁÈ· ÙÔ Ì¿ÓÈÔ ÙÔ˘ ·È‰ÈÔ‡ (¿ÓÙ· ÚÔËÁÂ›Ù·È ¤ÏÂÁ¯Ô˜ Ì ÙÔ ¯¤ÚÈ Ì·˜, ÙÔ ÔÔ›Ô ·Ê‹ÓÔ˘Ì ·ÚÎÂÙ‹ ÒÚ· ̤۷ ÛÙÔ ÓÂÚfi), Â) ·ÔÌ·ÎÚ‡ÓÔ˘Ì οı ›‰Ô˘˜ ËÏÂÎÙÚÈΤ˜ Û˘Û΢¤˜ ·fi ÙÔ Ì¿ÓÈÔ, ÛÙ) ÙÔÔıÂÙԇ̠·˘ÙÔÎfiÏÏËÙ· ÛÙ· Ù˙¿ÌÈ· ÛÙÔ ‡„Ô˜ ÙˆÓ Ì·ÙÈÒÓ ÙÔ˘ ·È‰ÈÔ‡, ÂÓÒ ˙) Û¯ÂÙÈο Ì ÙË ¯Ú‹ÛË ÙÔ˘ ·ÓÂÏ΢ÛÙ‹Ú·, Ì·ı·›ÓÔ˘Ì ÛÙÔ ·È‰› ÙË ¯Ú‹ÛË ÙÔ˘ ÎÔ˘‰Ô˘ÓÈÔ‡ Û˘Ó·ÁÂÚÌÔ‡ Î·È ÙÔ ·ÔÙÚ¤Ô˘Ì ¤ÓÙÔÓ· ·fi ÙÔ Ó· ·›˙ÂÈ Ì ÙÔ ÎÔ˘Ì› STOP, ·Ú¿ ÌfiÓÔ Â¿Ó ˘¿ÚÍÂÈ ·Ó¿ÁÎË (.¯. “È·ÛÙ›” fi‰È ‹ ¯¤ÚÈ) (2,63,64).

∞‰È·ÌÊÈÛ‚‹ÙËÙ·, ˆÛÙfiÛÔ, ·ÚÈÔ˜ ·Ú¿ÁÔÓÙ·˜ ÁÈ· ÙËÓ ·ÔÙÚÔ‹ ·Ù˘¯ËÌ¿ÙˆÓ Â›Ó·È Ë ·Ó·‰È·ÌfiÚʈÛË Ù˘ ·ÓıÚÒÈÓ˘ Û˘ÌÂÚÈÊÔÚ¿˜ (Ë ÌÂÙ·‚ÔÏ‹ Ù˘ ÓÔÔÙÚÔ›·˜ ÙÔ˘ ÏËı˘ÛÌÔ‡) Î·È Ô ÙÚfiÔ˜ Ô˘ ·˘Ù‹ ÌÔÚ› Ó· ‰È·ÙËÚËı› ÛÙÔÓ ¯ÚfiÓÔ: ·) Ì ‰È·Ú΋ ÂÓË̤ڈÛË, ‚) Ì ‰È·ÚΛ˜ ÂϤÁ¯Ô˘˜ ÂÊ·ÚÌÔÁ‹˜ ÙˆÓ ÓÔÌÔıÂÙËÌ¿ÙˆÓ, Á) ÌÂ Û˘Ó¯‹ Î·È ·‰È¿ÎÚÈÙË (¯ˆÚ›˜ ÂÍ·ÈÚ¤ÛÂȘ) ηٿ ÙÔÓ ÓfiÌÔ ÂÈ‚ÔÏ‹ ΢ÚÒÛÂˆÓ Î·È ‰) ÌÂ Û˘ÓÂȉËÙÔÔ›ËÛË Ù˘ Èı·ÓfiÙËÙ·˜ Ó· ˘Ô‚·ıÌÈÛÙ› - ‹ ·ÎfiÌ· Î·È Ó· ÛÙÂÚËı› - Ë ÔÈfiÙËÙ· ˙ˆ‹˜ ÂÓfi˜ ·È‰ÈÔ‡, ÂÍ·ÈÙ›·˜ Ì›·˜ “·Ï‹˜” ·Ì¤ÏÂÈ·˜.

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ORIGINAL ARTICLE

∞Ù˘¯‹Ì·Ù· Û ·È‰È¿ Û¯ÔÏÈ΋˜ ËÏÈΛ·˜ ÛÙËÓ fiÏË ÙˆÓ ¶·ÙÚÒÓ Î·Ù¿ Ù· ¤ÙË 2000 Î·È 2003 1 ∂ÚÁ·ÛÙ‹ÚÈÔ ÀÁÈÂÈÓ‹˜, π·ÙÚÈÎfi ∆Ì‹Ì· ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ 2 ™¯ÔÏ‹ ∂·ÁÁÂÏÌ¿ÙˆÓ ÀÁ›·˜, ∞.∆.∂.π. ¶·ÙÚÒÓ 3 ∂ÚÁ·ÛÙ‹ÚÈÔ º˘ÛÈÔÏÔÁ›·˜, π·ÙÚÈÎfi ∆Ì‹Ì·, ¢ËÌÔÎÚ›ÙÂÈÔ ¶·ÓÂÈÛÙ‹ÌÈÔ £Ú¿Î˘ 4 ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, “∫·Ú·Ì·Ó‰¿ÓÂÈÔ” °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ¶·ÙÚÒÓ AÏÏËÏÔÁÚ·Ê›·: πˆ¿ÓÓ˘ ¢ÂÙÔÚ¿Î˘ ∂ÚÁ·ÛÙ‹ÚÈÔ ÀÁÈÂÈÓ‹˜, π·ÙÚÈÎfi ∆Ì‹Ì· ¶·ÓÂÈÛÙËÌ›Ô˘ ¶·ÙÚÒÓ ∆.∫. 265 00 ∂-mail: pbhealth@med. upatras.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 05-07-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 28-03-2006

∞. ∞ÏÂÍfiÔ˘ÏÔ˜1, π. ¢ÂÙÔÚ¿Î˘1, ∂. ¢ÂÙÔÚ¿Î˘2, Ÿ. ¶·ÁˆÓÔÔ‡ÏÔ˘3, °. ∫ÚÔÎȉ¿˜4

¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‹Ù·Ó Ë Îˆ‰ÈÎÔÔ›ËÛË Î·È ·Ó¿Ï˘ÛË ÙˆÓ ÛÙÔȯ›ˆÓ ·fi Ù· ·Ú¯Â›· ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ÙˆÓ Â͈ÙÂÚÈÎÒÓ È·ÙÚ›ˆÓ ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶·ÙÚÒÓ, ÚÔÎÂÈ̤ÓÔ˘ Ó· ‰ÈÂÚ¢ÓËıÔ‡Ó Ù· ÂȉËÌÈÔÏÔÁÈο ÙÔ˘˜ ¯·Ú·ÎÙËÚÈÛÙÈο, Ì ÛÙfi¯Ô ÙË ‰È¢ÎÚ›ÓËÛË ÙˆÓ ·ÈÙÈÒÓ Ô˘ Ù· ÚÔηÏÔ‡Ó Î·È ÙË Ï‹„Ë ÚÔÏËÙÈÎÒÓ Ì¤ÙÚˆÓ. ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ÃÚËÛÈÌÔÔÈ‹ıËÎ·Ó Ù· ·Ú¯Â›· ηٷÁÚ·Ê‹˜ ÂÂÈÁfiÓÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ ÙˆÓ Â͈ÙÂÚÈÎÒÓ È·ÙÚ›ˆÓ ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·ÙÚÒÓ, ÙˆÓ ÂÙÒÓ 2000 Î·È 2003. ∏ ÛÙ·ÙÈÛÙÈ΋ ÂÂÍÂÚÁ·Û›· ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ¤ÁÈÓ Ì ÙË ‰ÔÎÈÌ·Û›· x2 Î·È ÙË ‰ÔÎÈÌ·Û›· Ù˘ ·Ó¿Ï˘Û˘ ηٿ Û˘ÛÙ¿‰Â˜. ∞ÔÙÂϤÛÌ·Ù·: ∞fi ÙȘ 2820 ÂÚÈÙÒÛÂȘ, ÔÛÔÛÙfi 62,1% ·ÊÔÚ¿ Û ·ÁfiÚÈ· Î·È 37,9% Û ÎÔÚ›ÙÛÈ· Û¯ÔÏÈ΋˜ ËÏÈΛ·˜ (6-12 ÂÙÒÓ). ∆· ·Ù˘¯‹Ì·Ù· ·ÊÔÚÔ‡Û·Ó Û ÙÒÛÂȘ (66,7%), ·Ù˘¯‹Ì·Ù· Ì ÌÂÙ·ÊÔÚÈÎfi ̤ÛÔ (15,4%), ‰ËÏËÙËÚÈ¿ÛÂȘ (0,43%), ËÏÂÎÙÚÔÏË͛˜ (0,4%) Î·È ÂÁη‡Ì·Ù· (0,2%). ∆· ÙÚ·‡Ì·Ù· ÂÓÙÔ›˙ÔÓÙ·Ó Î˘Ú›ˆ˜ ÛÙ· ¿Óˆ Î·È Î¿Ùˆ ¿ÎÚ· (29,3% Î·È 22%, ·ÓÙ›ÛÙÔȯ·), ηıÒ˜ Î·È ÛÙËÓ ÎÂÊ·Ï‹ (20%). ∆· ·Ù˘¯‹Ì·Ù· Û˘Ì‚·›ÓÔ˘Ó Î˘Ú›ˆ˜ ÛÙÔ Û›ÙÈ (36,1%), Û ¯ÒÚÔ˘˜ ̤۷ Î·È Á‡Úˆ ·fi ÙÔ Û¯ÔÏÂ›Ô (14,3%), Û ·È‰ÈΤ˜ ¯·Ú¤˜ (13,5%) ‹ ÛÙÔÓ ‰ÚfiÌÔ (10,9%), Û˘Ó‹ıˆ˜ ˘fi ÙËÓ Â›‚ÏÂ„Ë ÁÔÓ¤ˆÓ ‹ ÎˉÂÌfiÓˆÓ (67,4%). ∏ ·Ó¿Ï˘ÛË Î·Ù¿ Û˘ÛÙ¿‰Â˜ ·Ó¤‰ÂÈÍ ٤ÛÛÂÚȘ ÔÌ¿‰Â˜, Ì ÔÛÔÛÙ¿ Û˘ÌÌÂÙÔ¯‹˜ 37,7%, 39,5%, 10,2% Î·È 12,7% ·ÓÙ›ÛÙÔȯ·, Ô˘ ‰È·ÊÔÚÔÔÈÔ‡Ó Ù· ·Ù˘¯‹Ì·Ù· Ì ‚¿ÛË ÙÔÓ ÙfiÔ, ÙËÓ ËÏÈΛ·, ÙÔ Â›‰Ô˜, ÙËÓ ÂÓÙfiÈÛË, ·ÏÏ¿ Î·È ÙÔ˘˜ ·˘ÙfiÙ˜ Ì¿ÚÙ˘Ú˜. √ ̤ÛÔ˜ ·ÚÈıÌfi˜ ÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ ÙÔ ¤ÙÔ˜ 2000 ‹Ù·Ó 3,5 ·Ó¿ Ë̤ڷ, ÂÓÒ ÙÔ 2003 ‹Ù·Ó 4,2 ·Ó¿ Ë̤ڷ, ·˘ÍË̤ÓÔ˜ ηٿ 18%. ∏ ‰È·ÊÔÚ¿ ·˘Ù‹ ·ÊÔÚÔ‡Û ΢ڛˆ˜ Û ·‡ÍËÛË ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ Û˘Ó¤‚ËÛ·Ó ÛÙÔÓ ‰ÚfiÌÔ (·‡ÍËÛË 46,4%) Î·È ÛÙÔ Û›ÙÈ (·‡ÍËÛË 28,8%), ÂÓÒ ·ÍÈÔÛËÌ›ˆÙË ‹Ù·Ó Ë Ì›ˆÛË ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ÛÙ· Û¯ÔÏ›· ÙËÓ ›‰È· ÂÚ›Ô‰Ô (Ì›ˆÛË 25,3%). ™˘ÌÂÚ¿ÛÌ·Ù·: ∆· Â˘Ú‹Ì·Ù· Ù˘ ÌÂϤÙ˘ ÂȂ‚·ÈÒÓÔ˘Ó ·ÓÙ›ÛÙÔȯ· Â˘Ú‹Ì·Ù· ¿ÏÏˆÓ ÂÚ¢ÓÒÓ, Û‡Ìʈӷ Ì ٷ ÔÔ›· Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ‰È·ÊÔÚÔÔÈÂ›Ù·È ·Ó¿ÏÔÁ· Ì ÙÔ Ê‡ÏÔ, ÙËÓ ËÏÈΛ·, ÙÔÓ ÙfiÔ Î·È ÙËÓ ÂÔ¯‹ ÙÔ˘ ¤ÙÔ˘˜ Ô˘ ·˘Ù¿ Û˘Ó¤‚ËÛ·Ó. ¶·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë Ê‡ÛË ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ‰‡ÛÎÔÏ· ÂÈÙÚ¤ÂÈ ÙËÓ ÂÍ·ÁˆÁ‹ ·ÛÊ·ÏÒÓ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ, Ë ÁÂÓÈ΋ ÂÔ›ıËÛË Â›Ó·È fiÙÈ Û ÌÂÁ¿ÏÔ ‚·ıÌfi ÌÔÚÔ‡Ó Ó· ÚÔ‚ÏÂÊıÔ‡Ó Î·È Ó· ÂÚÈÔÚÈÛÙÔ‡Ó, ÙÔ˘Ï¿¯ÈÛÙÔÓ ÛÙ· Â›‰· ¿ÏÏˆÓ ¯ˆÚÒÓ, Ì ÙË Ï‹„Ë ÙˆÓ Î·Ù¿ÏÏËÏˆÓ Ì¤ÙÚˆÓ.

§¤ÍÂȘ ÎÏÂȉȿ: ¶·È‰Èο ·Ù˘¯‹Ì·Ù·, ÚfiÏË„Ë, ÂȉËÌÈÔÏÔÁ›· ·Ù˘¯ËÌ¿ÙˆÓ.

Accidents in children 6-12 years old in Patras during the years 2000 and 2003 1 Laboratory of Public Health, Medical School, University of Patras 2 School of Health Professions, Technical Institute of Patras 3 Laboratory of Physiology, Medical School, Democritus University of Thrace 4 ”Karamandanio” Children’s Hospital

¶·È‰È·ÙÚÈ΋ 2006;69:278-285

A. Alexopoulos1, I. Detorakis1, E. Detorakis2, O. Pagonopoulou3, G. Krokidas4

Abstract Background: The aim of this study was the evaluation of key epidemiological characteristics of children’s accidents in a major Greek city.

Methods: All available records concerning children’s injuries from the outpatient department of the “Karamandanio” Children’s Hospital in Patras, Greece, were recoded and analyzed, using descriptive statistics and chi-square and hierarchical cluster analysis.

Results: A total of 2,820 cases covering the years 2000 and 2003, were included, of which 62.1% involved boys and 37.9% girls aged 6 to 12 years. Fall related injuries (66.7%) predominated followed by traffic

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¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙËÓ fiÏË ÙˆÓ ¶·ÙÚÒÓ

accidents (15.4%), poisoning (0.43%), electric shock (0.4%) and burns (0.2%). Most of the trauma involved the upper and lower limbs (29.3% and 22%, respectively) and the head (20%). In 36.1% of cases the accident occurred at home, 14.3% at school (inside or outside), 13.5% in public playgrounds and 10.9% in the street, and usually the parents were present (67.4%). Hierarchical cluster analysis using sex, place, age, type, localization and presence of eye witness as variables, revealed four discrete clusters which accounted for 37.7%, 39.5%, 10.2% and 12.7% of all injuries respectively. In the year 2000 there were 3.5 admissions per day, while in 2003 there was an increase to 4.2 per day, mainly as a result of an increase in street accidents (by 46.6%) and home accidents (by 28.8%). Conversely there was a notable decrease in accidents occurring at school (by 25.3%). All the other findings of the study were in accordance with earlier reports on the different frequencies of injuries according to the sex, the age group and the season.

Conclusions: This retrospective study confirms that the majority of childhood accidents are environment related, and therefore theoretically preventable when sound strategies are implemented.

Correspondence: Ioannis Detorakis Laboratory of Public Health Medical School, University of Patras 26500, Patras Greece E-mail: pbhealth@med.upatras.gr Date of submission: 05-07-2005 Date of approval: 28-03-2006

Key words: Child injury, prevention, injury epidemiology.

∂ÈÛ·ÁˆÁ‹

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ

∆· ·È‰Èο ·Ù˘¯‹Ì·Ù· ·ÔÙÂÏÔ‡Ó ÛÔ‚·Úfi Úfi‚ÏËÌ· ‰ËÌfiÛÈ·˜ ˘Á›·˜ ‰Â‰Ô̤ÓÔ˘ fiÙÈ Û˘ÓÈÛÙÔ‡Ó ÙËÓ Î‡ÚÈ· ·ÈÙ›· ı·Ó¿ÙÔ˘ ·È‰ÈÒÓ ÛÙȘ ¯ÒÚ˜ Ù˘ ∂˘Úˆ·˚΋˜ ŒÓˆÛ˘ (1-4). ∏ ‰ÈÂÚ‡ÓËÛË ÙˆÓ ÂȉËÌÈÔÏÔÁÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Û˘Ì‚¿ÏÏÂÈ ÛÙË ‰È¢ÎÚ›ÓËÛË ÙˆÓ ·ÈÙ›ˆÓ Ô˘ Ù· ÚÔηÏÔ‡Ó Î·È ÙË Ï‹„Ë Ì¤ÙÚˆÓ ÚfiÏË„‹˜ ÙÔ˘˜. ¶ÚÔÛ¿ıÂȘ ÚÔ˜ ·˘Ù‹ ÙËÓ Î·Ù‡ı˘ÓÛË ‚Ú›ÛÎÔÓÙ·È Û ÂͤÏÈÍË ÙËÓ ÙÂÏÂ˘Ù·›· ‰ÂηÂÙ›· Û ·ÓÂ˘Úˆ·˚Îfi, ·ÏÏ¿ Î·È ÂıÓÈÎfi Â›‰Ô, fiˆ˜ Â›Ó·È ÁÈ· ·Ú¿‰ÂÈÁÌ· Ë ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ EDISS, ÙËÓ ÔÔ›· ‰ËÌÈÔ‡ÚÁËÛÂ Î·È ‰È·¯ÂÈÚ›˙ÂÙ·È ÙÔ ∫¤ÓÙÚÔ ŒÚ¢ӷ˜ Î·È ¶ÚfiÏ˄˘ ¶·È‰ÈÎÒÓ ∞Ù˘¯ËÌ¿ÙˆÓ (∫∂¶¶∞) Ì ·ÍÈÔÛËÌ›ˆÙ· ·ÔÙÂϤÛÌ·Ù· (5). ¶·ÚfiÌÔȘ ÂÚ¢ÓËÙÈΤ˜ ÚÔÛ¿ıÂȘ, ·ÎfiÌË Î·È Û ÌÈÎÚfiÙÂÚË Îϛ̷η, ı· ÌÔÚÔ‡Û·Ó Ó· Û˘Ì‚¿ÏÔ˘Ó ÛÙËÓ ÂÚ·ÈÙ¤Úˆ ηٷÓfiËÛË ÙÔ˘ ȉȷ›ÙÂÚÔ˘ ·˘ÙÔ‡ ÚÔ‚Ï‹Ì·ÙÔ˜ (6) Î·È ÛÙËÓ ·‡ÍËÛË Ù˘ ¢·ÈÛıËÛ›·˜ ÙˆÓ ·ÚÌfi‰ÈˆÓ ·Ú¯ÒÓ ÁÈ· ÙËÓ Â͇ÚÂÛË Ï‡ÛÂˆÓ Ì¤Ûˆ ηٿÏÏËÏˆÓ ·ÚÂÌ‚¿ÛÂˆÓ ÚfiÏ˄˘. ™ÙÔ Ï·›ÛÈÔ ·˘Ùfi, Ë ·ÚÔ‡Û· ÂÚÁ·Û›· ‰ÈÂÚÂ˘Ó¿ Ù· ÂȉËÌÈÔÏÔÁÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ, fiˆ˜ ·˘Ù¿ ηٷÁÚ¿ÊËÎ·Ó ÛÙ· Â͈ÙÂÚÈο È·ÙÚ›· ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ Ù˘ ¶¿ÙÚ·˜ ηٿ Ù· ¤ÙË 2000 Î·È 2003, ˆ˜ ÌÈ· ÂÏ¿¯ÈÛÙË ÚÔÛ¿ıÂÈ· Û˘Ì‚ÔÏ‹˜ ÛÙÔÓ ·ÁÒÓ· ÁÈ· ÙËÓ ÚfiÏË„Ë ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ.

∏ ¤Ú¢ӷ ÛÙËÚ›¯ıËΠÛÙ· ·Ú¯Â›· ·Ù˘¯ËÌ¿ÙˆÓ ÙˆÓ Â͈ÙÂÚÈÎÒÓ È·ÙÚ›ˆÓ ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶·ÙÚÒÓ ÙˆÓ ÂÙÒÓ 2000 Î·È 2003, Ù· ÔÔ›· ‹Ù·Ó ‰È·ı¤ÛÈÌ· Î·È Ù· ÔÔ›· Ï¿‚·Ì ÌÂÙ¿ ·fi Û¯ÂÙÈ΋ ¿‰ÂÈ· Ù˘ ‰ÈÔ›ÎËÛ˘ ÙÔ˘ π‰Ú‡Ì·ÙÔ˜. √È Î·Ù·Áڷʤ˜ ·˘Ù¤˜ Έ‰ÈÎÔÔÈ‹ıËÎ·Ó Î·Ù¿ÏÏËÏ· Î·È ÂÈÛ‹¯ıËÛ·Ó Û ËÏÂÎÙÚÔÓÈ΋ ‚¿ÛË ÚÔ˜ ÂÂÍÂÚÁ·Û›·. √È ÌÂÙ·‚ÏËÙ¤˜ Ô˘ ÂÚÈÂÏ¿Ì‚·Ó·Ó Ù· ·Ú¯Â›· ·˘Ù¿ ·ÊÔÚÔ‡Û·Ó ÙfiÛÔ Û ·ÙÔÌÈο ·ÓÙÈÎÂÈÌÂÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ οı ·È‰ÈÔ‡ (ʇÏÔ, ËÏÈΛ·, Ù¿ÍË Û¯ÔÏ›Ԣ), fiÛÔ Î·È Û ‰Â‰Ô̤ӷ ÙÔ˘ ÔÈÎÔÁÂÓÂÈ·ÎÔ‡ ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ (ÔÈÎÔÁÂÓÂȷ΋ ηٿÛÙ·ÛË Î·È ÌÔÚʈÙÈÎfi Â›Â‰Ô ÁÔÓ¤ˆÓ, ‡·ÚÍË ‹ ÌË ·‰ÂÏÊÒÓ, ··Û¯fiÏËÛË ÌËÙ¤Ú·˜, ÛÂÈÚ¿ Á¤ÓÓËÛ˘ ÙÔ˘ ·È‰ÈÔ‡), Û ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ (ËÌÂÚÔÌËÓ›·, ÙfiÔ˜, ÒÚ·, ›‰Ô˜ ‹ ı¤ÛË Î¿ÎˆÛ˘), ηıÒ˜ Î·È Û ÔÚÈṲ̂ӷ ˘ÔÎÂÈÌÂÓÈο ÛÙÔȯ›· Ù· ÔÔ›· ·Ó·Ê¤ÚıËÎ·Ó ·fi ÙÔÓ ÁÔÓ¤· ‹ ¿ÏÏÔ Û˘ÓÔ‰fi ÙÔ˘ ·È‰ÈÔ‡ ηٿ ÙËÓ ÚÔۤϢÛË (¯·Ú·ÎÙËÚÈÛÙÈο Û˘ÌÂÚÈÊÔÚ¿˜ ÙÔ˘ ·È‰ÈÔ‡, ÁÂÓÈ΋ Û¯ÔÏÈ΋ Â›‰ÔÛË, Û¯¤ÛË Ì ÙÔ ·È‰› fiÛˆÓ ‹Ù·Ó ·ÚfiÓÙ˜ ÛÙÔ ·Ù‡¯ËÌ·, ÈÛÙÔÚÈÎfi ·Ù˘¯‹Ì·ÙÔ˜/·Ù˘¯ËÌ¿ÙˆÓ Ô˘ ¯ÚÂÈ¿ÛÙËÎÂ/·Ó Â›Û˘ È·ÙÚÈ΋ ÊÚÔÓÙ›‰· ηٿ ÙÔ ·ÚÂÏıfiÓ). ∆· ÙÂÏÂ˘Ù·›· ÛÙÔȯ›· ıˆڋıËÎ·Ó ˘ÔÎÂÈÌÂÓÈο, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ·Ë¯Ô‡Û·Ó ÙËÓ ÚÔÛˆÈ΋ ÁÓÒÌË ÙÔ˘ Û˘ÓÔ‰Ô‡ Î·È Ë ‰È·ÛÙ·‡ÚˆÛË Ù˘ ·ÎÚ›‚ÂÈ¿˜ ÙÔ˘˜ ‰ÂÓ ‹Ù·Ó ‰˘Ó·Ù‹. ∆Ô ÌÔÚʈÙÈÎfi Â›Â‰Ô ÙˆÓ ÁÔÓ¤ˆÓ Έ‰ÈÎÔÔÈ‹ıËΠ·Ó¿ÏÔÁ· Ì ÙÔ ·ÔÏ˘Ù‹ÚÈÔ Ô˘ ·˘ÙÔ› ηÙ›¯·Ó. ™˘ÓÔÏÈο, Î·È ÁÈ· Ù· ‰‡Ô ¤ÙË Û˘ÁÎÂÓÙÚÒıËÎ·Ó 2820 ηٷÁڷʤ˜, 1294 ÁÈ· ÙÔ ¤ÙÔ˜ 2000 Î·È 1526 ÁÈ· ÙÔ ¤ÙÔ˜ 2003. ¢˘ÛÙ˘¯Ò˜, ÚÔÁÂÓ¤ÛÙÂÚ˜ ‹ ¤ÛÙˆ ÂӉȿÌÂÛ˜ ηٷÁڷʤ˜ ‰ÂÓ ‹Ù·Ó ‰È·ı¤ÛÈ̘ ·fi Ù· ·Ú¯Â›· ÙÔ˘ ¡ÔÛÔÎÔÌ›Ԣ Î·È ‰ÂÓ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË. ™ÙȘ 848 ÂÚÈÙÒÛÂȘ (30%) ÔÈ Î·Ù·Áڷʤ˜ ‹Ù·Ó Ï‹ÚÂȘ ··ÓÙ‹ÛÂˆÓ Û fiÏ· Ù· ‰›·, ÂÓÒ ·fi ÙȘ ˘fiÏÔÈ˜ ¤ÏÂÈ·Ó ÛÙÔȯ›·, ÂÂȉ‹ ÔÈ Û˘ÓÔ‰Ô› ‰ÂÓ ÂÈı˘ÌÔ‡Û·Ó ‹ ‰ÂÓ ‹Ù·Ó Û ı¤ÛË Ó· Ù· ·Ú¿Û¯Ô˘Ó. ™Ù· ·Ú¯Â›· Ô˘ ‹Ù·Ó ‰È·ı¤ÛÈÌ· ¶·È‰È·ÙÚÈ΋ 2006;69:278-285

280

∞. ∞ÏÂÍfiÔ˘ÏÔ˜ Î·È Û˘Ó.

‰ÂÓ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·Ó Ù· ÛÔ‚·Ú¿ ÂÚÈÛÙ·ÙÈο Ô˘ ··ÈÙÔ‡Û·Ó ÙÚÈÙÔ‚¿ıÌÈ· ÊÚÔÓÙ›‰· Î·È Ù· ÔÔ›· ÂÈÛ‹¯ıËÛ·Ó ÛÙ· ‰‡Ô ·ÚÈ· ÓÔÛÔÎÔÌ›· Ù˘ ÂÚÈÔ¯‹˜ (°ÂÓÈÎfi ∫Ú·ÙÈÎfi Î·È ¶ÂÚÈÊÂÚÂÈ·Îfi ¶·ÓÂÈÛÙËÌÈ·Îfi ¶·ÙÚÒÓ), ηıÒ˜ Î·È fiÏ· Ù· ·È‰È¿ ÙˆÓ ÔÔ›ˆÓ Ë ËÏÈΛ· ‹Ù·Ó ÌÈÎÚfiÙÂÚË ÙˆÓ 6 ‹ ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 12 ÂÙÒÓ. √ ÛÙ·ÙÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ·ÊÔÚÔ‡Û ÛÙȘ Û˘ÁÎÚ›ÛÂȘ ÈÓ·ÎÔÔÈËÌ¤ÓˆÓ ÙÈÌÒÓ (›Ó·Î˜ Û˘Ó¿ÊÂÈ·˜) Ì ÙË ‰ÔÎÈÌ·Û›· x2 Î·È ÙËÓ ÔÌ·‰ÔÔ›ËÛË ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÁÈ· ÙËÓ ·Ó¿‰ÂÈÍË ‰È·ÎÚÈÙÒÓ ÔÌ¿‰ˆÓ Ì ÎÔÈÓ¿ ¯·Ú·ÎÙËÚÈÛÙÈο Ì ÙË ‰ÔÎÈÌ·Û›· ·Ó¿Ï˘Û˘ ηٿ Û˘ÛÙ¿‰Â˜ (ÈÂÚ·Ú¯È΋ Ù·ÍÈÓfiÌËÛË). ∆fiÛÔ Ë ÂÚÈÁÚ·ÊÈ΋ fiÛÔ Î·È Ë ÂÎÙÈÌËÙÈ΋ ÛÙ·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË Ú·ÁÌ·ÙÔÔÈ‹ıËÎ·Ó Ì ÙÔ ÏÔÁÈÛÌÈÎfi ·Î¤ÙÔ SPSS (v12, 2004).

∞ÔÙÂϤÛÌ·Ù· ∞fi ÙȘ 2820 ÂÚÈÙÒÛÂȘ, ÔÈ 1751 (62,1%) ·ÊÔÚÔ‡Û·Ó Û ·ÁfiÚÈ· Î·È ÔÈ 1069 (37,9%) Û ÎÔÚ›ÙÛÈ· ËÏÈΛ·˜ 6-12 ÂÙÒÓ. ™ÙÔÓ ¶›Ó·Î· 1 ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· ÎÔÈÓˆÓÈÎÔ-‰ËÌÔÁÚ·ÊÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·Ù˘¯ËÌ·ÙÈÒÓ, fiˆ˜ Ë ËÏÈΛ·, ÙÔ Ê‡ÏÔ Î·ıÒ˜ Î·È Ù· ¯ÚÔÓÈο ‰Â‰Ô̤ӷ ÙÔ˘ ÂÚÈÛÙ·ÙÈÎÔ‡. º·›ÓÂÙ·È fiÙÈ Ù· ÂÚÈÛÛfiÙÂÚ· ·fi ·˘Ù¿ ·ÊÔÚÔ‡Ó Û ·ÁfiÚÈ·, Ì ·È¯Ì¤˜ ÙȘ ËÏÈ˘ ÙˆÓ 6, 10 Î·È 12 ÂÙÒÓ. ∆Ô 2000 Ë Ì¤ÛË ËÌÂÚ‹ÛÈ· Û˘¯ÓfiÙËÙ· ÂÚÈÛÙ·ÙÈÎÒÓ ‹Ù·Ó 3,5/Ë̤ڷ, ÂÓÒ ÙÔ 2003 ÂÌÊ·Ó›˙ÂÙ·È ·˘ÍË̤ÓË Û 4,2/Ë̤ڷ (+18%). ™¯Â‰fiÓ ¤Ó· ÛÙ· ÙÚ›· ·Ù˘¯‹Ì·Ù· Û˘Ó¤‚Ë Î·Ù¿ ÙÔ˘˜ ·ÚÈÓÔ‡˜ Ì‹Ó˜ (30,3%) ηıÒ˜ Î·È ÙȘ ·ÔÁÂ˘Ì·ÙÈÓ¤˜ ÒÚ˜ (29,1%), ÂÓÒ ‰ÂÓ ·ÚÔ˘ÛÈ¿˙ÂÙ·È È‰È·›ÙÂÚË Û˘ÛÛÒÚ¢ÛË ·Ù˘¯ËÌ¿ÙˆÓ Û οÔÈ· ·fi ÙȘ Ë̤Ú˜ Ù˘ ‚‰ÔÌ¿‰·˜. ŸÛÔÓ ·ÊÔÚ¿ ÛÙÔ Â›‰Ô˜ ÙÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ (¶›Ó·Î·˜ 2), ·˘Ù¿ ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ÙÔ˘˜ ·ÊÔÚÔ‡Ó Û ÙÒÛÂȘ (66,7%), Ì ٷ ·Ù˘¯‹Ì·Ù· ·fi ÌÂÙ·ÊÔÚÈÎfi ̤ÛÔ Ó· ¤ÔÓÙ·È (15,4%). ªÈÎÚfiÙÂÚ· ÔÛÔÛÙ¿ ·È‰ÈÒÓ ˘¤ÛÙËÛ·Ó ·Ù˘¯‹Ì·Ù· Ô˘ ÔÊ›ÏÔÓÙ·Ó Û ‰ËÏËÙËÚÈ¿ÛÂȘ (0,43%), ËÏÂÎÙÚÔÏË͛˜ (0,4% ) Î·È ÂÁη‡Ì·Ù· ΢ڛˆ˜ ·fi ¯Ú‹ÛË ‚ÂÁÁ·ÏÈÎÒÓ (0,20%). ∏ ÂÓÙfiÈÛË ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜ ·ÊÔÚÔ‡Û ΢ڛˆ˜ Û ηÎÒÛÂȘ ÛÙ· ¿Óˆ Î·È Î¿Ùˆ ¿ÎÚ· (29,3% Î·È 22,0%, ·ÓÙ›ÛÙÔȯ·), ηıÒ˜ Î·È ÛÙËÓ ÎÂÊ·Ï‹ (20,0%). ™ÙÔÓ ¶›Ó·Î· 3 ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÔÚÈṲ̂ӷ ·fi Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ‰Â›ÁÌ·ÙÔ˜, Ù· ÔÔ›· ıˆÚÔ‡ÓÙ·È ˆ˜ Èı·ÓÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Î·È ÙˆÓ ÔÔ›ˆÓ Ë ÛËÌ·Û›· ¤¯ÂÈ ·ÔÙÂϤÛÂÈ ·ÓÙÈΛÌÂÓÔ ¤Ú¢ӷ˜ Î·È ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜ (7-9). ∆· ÛÙÔȯ›· ·˘Ù¿, ·Ó Î·È ÛÙËÓ ·ÚÔ‡Û· ¤Ú¢ӷ ‰ÂÓ ·ÊÔÚÔ‡Ó ÛÙÔ Û‡ÓÔÏÔ ÙÔ˘ ‰Â›ÁÌ·ÙÔ˜, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÌfiÓÔ Ô ¤Ó·˜ ÛÙÔ˘˜ ÙÚÂȘ Û˘ÓÔ‰Ô‡˜ ·¿ÓÙËÛ ÛÙȘ ·ÓÙ›ÛÙÔȯ˜ ¶·È‰È·ÙÚÈ΋ 2006;69:278-285

¶›Ó·Î·˜ 1. ∫·Ù·ÓÔÌ‹ ÙˆÓ 2820 ÂÚÈÛÙ·ÙÈÎÒÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ ηٷÁÚ¿ÊËÎ·Ó ÛÙ· Â͈ÙÂÚÈο È·ÙÚ›· ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶·ÙÚÒÓ Ù· ¤ÙË 2000 Î·È 2003, Ì ‚¿ÛË ‰ËÌÔÁÚ·ÊÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·È‰ÈÒÓ Î·È ¯ÚÔÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ ¶·Ú¿ÌÂÙÚÔ˜ ∏ÏÈΛ· 6-9 10-12 ™‡ÓÔÏÔ º‡ÏÔ ∞ÁfiÚÈ· ∫ÔÚ›ÙÛÈ· ™‡ÓÔÏÔ ŒÙÔ˜ ·Ù˘¯‹Ì·ÙÔ˜ 2000 2003 ™‡ÓÔÏÔ ∂Ô¯‹ ÃÂÈÌÒÓ·˜ ÕÓÔÈÍË ∫·ÏÔη›ÚÈ ºıÈÓfiˆÚÔ ™‡ÓÔÏÔ ∏̤ڷ ·Ù˘¯‹Ì·ÙÔ˜ ™·‚‚·ÙÔ·ÚÈ·ÎÔ ∫·ıËÌÂÚÈÓ‹ ™‡ÓÔÏÔ ÃÚÔÓÈ΋ ÛÙÈÁÌ‹ ¶Úˆ› (6:00-12:00) ªÂÛË̤ÚÈ (12:00-17:00) ∞fiÁÂ˘Ì· (17:00-20:00) µÚ¿‰˘ (20:00-6:00) ™‡ÓÔÏÔ

¡

¶ÔÛÔÛÙfi (%)

1490 1330 2820

52,8 47,2 100,0

1751 1069 2820

62,1 37,9 100,0

1294 1526 2820

45,9 54,1 100,0

674 855 647 644 2820

23,9 30,4 22,9 22,8 100,0

712 2108 2820

25,2 74,8 100,0

601 771 820 628 2820

21,3 27,3 29,1 22,3 100,0

ÂÚˆÙ‹ÛÂȘ, ıˆÚÂ›Ù·È fiÙÈ Â›Ó·È Èηӿ Ó· ·ÔÙÂϤÛÔ˘Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ ÙË ‚¿ÛË ÁÈ· ÚÔ‚ÏËÌ·ÙÈÛÌfi. ŒÙÛÈ, ·Ú·ÙËÚÂ›Ù·È fiÙÈ ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ÙÔ˘ ‰Â›ÁÌ·ÙÔ˜ ·ÊÔÚ¿ Û ·È‰È¿ ΢ڛˆ˜ ÙˆÓ ‰‡Ô ÚÒÙˆÓ Ù¿ÍÂˆÓ ÙÔ˘ ‰ËÌÔÙÈÎÔ‡ (41,2%), ÙˆÓ ÔÔ›ˆÓ ÔÈ ÁÔÓ›˜ Â›Ó·È ·fiÊÔÈÙÔÈ ÚˆÙÔ‚¿ıÌÈ·˜ ‹ ‰Â˘ÙÂÚÔ‚¿ıÌÈ·˜ ÂÎ·›‰Â˘Û˘ Î·È ÔÈ ÌËÙ¤Ú˜ ÙÔ˘˜ - ˆ˜ Â› ÙÔ Ï›ÛÙÔÓ (71,8%) ÂÚÁ·˙fiÌÂÓ˜. ∞Ó Î·È ‰ÂÓ ·ÔÙÂÏ› ·ÍÈfiÈÛÙÔ ÛÙÔȯ›Ô, ÂÓÙ‡ˆÛË ÚÔηÏ› ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Û ÔÛÔÛÙfi 73% ÔÈ Û˘ÓÔ‰Ô› ÙˆÓ ·È‰ÈÒÓ Â¤ÏÂÍ·Ó ÙË Ï¤ÍË “¿Ù·ÎÙÔ” ÁÈ· Ó· ÂÚÈÁÚ¿„Ô˘Ó ·‰Ú¿ ÙËÓ ÚÔÛˆÈÎfiÙËÙ· ÙÔ˘ ·È‰ÈÔ‡ Û ۯÂÙÈ΋ ÂÚÒÙËÛË Ô˘ ÙÔ˘˜ ›¯Â ÙÂı›. ™ÙËÓ ÏÂÈÔ„ËÊ›· ÙÔ˘˜ (77,6%) Ù· ·È‰È¿ ‰ÂÓ Â›¯·Ó ÈÛÙÔÚÈÎfi ÚÔËÁÔ‡ÌÂÓÔ˘ ÛÔ‚·ÚÔ‡ ·Ù˘¯‹Ì·ÙÔ˜. √ ÙÚ·˘Ì·ÙÈÛÌfi˜ ›¯Â Û˘Ì‚Â› ΢ڛˆ˜ ÛÙÔ Û›ÙÈ (36,1%), ·ÏÏ¿ Î·È Û ¯ÒÚÔ˘˜ ̤۷ Î·È Á‡Úˆ ·fi ÙÔ Û¯ÔÏÂ›Ô (14,3%), Û ·È‰ÈΤ˜ ¯·Ú¤˜ (13,5%) ‹ ÛÙÔÓ ‰ÚfiÌÔ (10,9%). øÛÙfiÛÔ, Û οı ÂÚ›ÙˆÛË Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ

281

¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙËÓ fiÏË ÙˆÓ ¶·ÙÚÒÓ

¶›Ó·Î·˜ 2. ∫·Ù·ÓÔÌ‹ ÙˆÓ 2820 ÂÚÈÛÙ·ÙÈÎÒÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ ηٷÁÚ¿ÊËÎ·Ó ÛÙ· Â͈ÙÂÚÈο È·ÙÚ›· ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶·ÙÚÒÓ Ù· ¤ÙË 2000 ¶·Ú¿ÌÂÙÚÔ˜ ∂›‰Ô˜ ·Ù˘¯‹Ì·ÙÔ˜ ¶ÙÒÛË ªÂÙ·ÊÔÚÈÎfi ̤ÛÔ ∞ȯÌËÚ¿ Î·È ‰ÈÂÈÛ‰˘ÙÈο ·ÓÙÈΛÌÂÓ· ∂ÎÚËÎÙÈÎfi ˘ÏÈÎfi ∫·˘Ù‹ ‡ÏË ‹ ·ÓÙÈΛÌÂÓÔ ∏ÏÂÎÙÚÈÎfi Ú‡̷ ¢ËÏËÙËÚ›·ÛË ·fi Ê¿Ú̷η ¢ËÏËÙËÚ›·ÛË ·fi ÙÚÔÊ‹ ¢‹ÁÌ· ˙ÒÔ˘ ™‡ÓÔÏÔ £¤ÛË/›‰Ô˜ ÙÚ·‡Ì·ÙÔ˜ ∫ÂÊ·Ï‹ ÕÓˆ ¿ÎÚ· ∫¿Ùˆ ¿ÎÚ· ¶ÔÏÏ·Ïfi ÙÚ·‡Ì· ∂Í¿ÚıÚËÌ·, ‰È¿ÛÙÚÂÌÌ· ∞ÓÔȯÙfi ÙÚ·‡Ì· ªÒψ˜ ÕÏÏÔ ™‡ÓÔÏÔ

¡

¶ÔÛÔÛÙfi (%)

¶›Ó·Î·˜ 3. ∫·Ù·ÓÔÌ‹ ÙˆÓ 2820 ÂÚÈÛÙ·ÙÈÎÒÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ ηٷÁÚ¿ÊËÎ·Ó ÛÙ· Â͈ÙÂÚÈο È·ÙÚ›· ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶·ÙÚÒÓ Ù· ¤ÙË 2000 Î·È 2003, ·Ó¿ÏÔÁ· Ì ÙÔ˘˜ Èı·ÓÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ¶·Ú¿ÌÂÙÚÔ˜

1880 433 266

66,67 15,35 9,43

6 77 10 10 1 137 2820

0,21 2,73 0,35 0,35 0,04 4,86 100,0

564 825 619 82 74 346 92 218 2820

20,0 29,26 21,95 2,91 2,62 12,27 3,26 7,73 100,0

Û˘Ó¤‚Ë ·Ú¿ ÙËÓ Â›‚ÏÂ„Ë ÁÔÓ¤ˆÓ ‹ Û˘ÁÁÂÓÒÓ (67,4%). ∏ ·Ó¿Ï˘ÛË Î·Ù¿ Û˘ÛÙ¿‰Â˜ Ì ÈÂÚ·Ú¯È΋ Ù·ÍÈÓfiÌËÛË - ÁÈ· ÙȘ ÌÂÙ·‚ÏËÙ¤˜ fiÔ˘ ‹Ù·Ó ‰È·ı¤ÛÈÌ· Ï‹ÚË ‰Â‰Ô̤ӷ - ·¤‰ˆÛ ٤ÛÛÂÚȘ ÔÌ¿‰Â˜ (¶›Ó·Î·˜ 4). ∏ ÚÒÙË (37,7%) ·ÊÔÚ¿ Û ·È‰È¿ (ËÏÈΛ·˜ 6-9 ÂÙÒÓ) ÛÙ· ÔÔ›· Ù· ·Ù˘¯‹Ì·Ù· Û˘Ó¤‚ËÛ·Ó Î˘Ú›ˆ˜ ÛÙÔ Û›ÙÈ Î·È ÂÚÈÂÏ¿Ì‚·Ó·Ó ÙÒÛÂȘ, ÂÁη‡Ì·Ù·, ËÏÂÎÙÚÔÏË͛˜, ‰ËÏËÙËÚÈ¿ÛÂȘ Î·È ÙÚ·‡Ì·Ù· ·fi ·È¯ÌËÚ¿ ·ÓÙÈΛÌÂÓ· ΢ڛˆ˜ ˘fi ÙËÓ Â›‚ÏÂ„Ë ÁÔÓ¤ˆÓ ‹ Û˘ÁÁÂÓÒÓ, ¯ˆÚ›˜ Âԯȷ΋ ‰È·Î‡Ì·ÓÛË. ∆Ë ‰Â‡ÙÂÚË ÔÌ¿‰· (39,5%) ··ÚÙ›˙Ô˘Ó ·È‰È¿ ÌÂÁ·Ï‡ÙÂÚ˘ ËÏÈΛ·˜ (9-12 ÂÙÒÓ), Û˘Ó‹ıˆ˜ ·ÁfiÚÈ·, Ù· ÔÔ›· ÙÚ·˘Ì·Ù›˙ÔÓÙ·È Û ·È‰ÈΤ˜ ¯·Ú¤˜, ÛÙËÓ ‡·ÈıÚÔ ‹ Û ¿ÏÏÔ˘˜ ¯ÒÚÔ˘˜. ∂Ó ÚÔÎÂÈ̤ӈ, Ù· ÂÚÈÛÛfiÙÂÚ· ·Ù˘¯‹Ì·Ù· ÚÔηÏÔ‡ÓÙ·È ·fi ÙÒÛÂȘ, ·fi ·È¯ÌËÚ¿ ‹ ‰ÈÂÈÛ‰˘ÙÈο ·ÓÙÈΛÌÂÓ· Î·È ·fi ‰‹ÁÌ·Ù· ˙ÒˆÓ ‹ ÂÓÙfïÓ. ∞˘Ù¿ Ê·›ÓÂÙ·È Ó· Û˘Ì‚·›ÓÔ˘Ó Î˘Ú›ˆ˜ ÙÔ Î·ÏÔη›ÚÈ Î·È ·ÚfiÓÙ˜ ÛÙÔ Û˘Ì‚¿Ó Â›Ó·È Û˘Ó‹ıˆ˜ ÙÚ›ÙÔÈ (.¯. Û˘ÓÔÌ‹ÏÈÎÔÈ) Î·È ÏÈÁfiÙÂÚÔ Û˘¯Ó¿ ÁÔÓ›˜ ‹ Û˘ÁÁÂÓ›˜. ∏ ÙÚ›ÙË ÔÌ¿‰· (10,2%) ·ÊÔÚ¿ Û ·Ù˘¯‹Ì·Ù· Ô˘ Û˘Ó¤‚ËÛ·Ó ÛÙÔÓ ‰ÚfiÌÔ Ì ÌÂÙ·ÊÔÚÈο ̤۷, ÙËÓ ¿ÓÔÈÍË ‹ ÙÔ Î·ÏÔη›ÚÈ, ·ÚÔ˘Û›· ÁÔÓ¤ˆÓ ‹ Û˘ÁÁÂÓÒÓ Î·È ·ÊÔÚÔ‡Ó Û ·È‰È¿ ËÏÈΛ·˜ 9-12 ÂÙÒÓ.

¡

¶ÔÛÔÛÙfi (%)

∆¿ÍË ÊÔ›ÙËÛ˘ (¢ËÌÔÙÈÎfi) 1Ë-2Ë 1163 41,2 3Ë-4Ë 802 28,4 5Ë-6Ë 855 30,3 ™‡ÓÔÏÔ 2820 100,0 ªÔÚʈÙÈÎfi Â›Â‰Ô ·Ù¤Ú· ∞/‚¿ıÌÈÔ - µ/‚¿ıÌÈÔ 668 81,0 °/‚¿ıÌÈÔ 157 19,0 ™‡ÓÔÏÔ (825) 100,0 ªÔÚʈÙÈÎfi Â›Â‰Ô ÌËÙ¤Ú·˜ ∞/‚¿ıÌÈÔ - µ/‚¿ıÌÈÔ 713 86,7 °/‚¿ıÌÈÔ 109 13,3 ™‡ÓÔÏÔ (822) 100,0 √ÈÎÔÁÂÓÂȷ΋ ηٿÛÙ·ÛË ÁÔÓ¤ˆÓ ŒÁÁ·ÌÔÈ 686 92,3 ¢È·˙¢Á̤ÓÔÈ 50 6,7 ™‡ÓÔÏÔ (736) 100,0 ∞·Û¯fiÏËÛË ÌËÙ¤Ú·˜ ∂ÚÁ·˙fiÌÂÓË 609 71,8 √ÈÎȷο 239 28,2 ™‡ÓÔÏÔ (848) 100,0 ⁄·ÚÍË ‹ ÌË ·‰ÂÏÊÒÓ ªÔÓ·¯Ô·›‰È 160 18,9 1 424 50,0 2 233 27,5 3 31 3,7 ™‡ÓÔÏÔ (848) 100,0 πÛÙÔÚÈÎfi ·Ù˘¯‹Ì·ÙÔ˜ ¯Ú‹˙ÔÓÙÔ˜ È·ÙÚÈ΋˜ ÊÚÔÓÙ›‰·˜ ªÂ ÈÛÙÔÚÈÎfi 632 22,4 ÚÔÁÂÓ¤ÛÙÂÚÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ Èڛ˜ ÈÛÙÔÚÈÎfi 2188 77,6 ÚÔÁÂÓ¤ÛÙÂÚÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ ™‡ÓÔÏÔ 2820 100,0 ¶·ÚfiÓÙ˜ ÛÙÔ ·Ù‡¯ËÌ· ∫·Ó¤Ó·˜ 71 2,5 °ÔÓ›˜ 1403 49,8 ™˘ÁÁÂÓ›˜ 495 17,6 √ÈÎȷ΋ ‚ÔËıfi˜, ʇϷη˜ 25 0,9 ÕÏÏÔÈ 826 29,3 ™‡ÓÔÏÔ 2820 100,0 ÃÒÚÔ˜ ·Ù˘¯‹Ì·ÙÔ˜ ™›ÙÈ 1018 36,1 ™¯ÔÏÂ›Ô (̤۷ ‹ Á‡Úˆ) 402 14,3 ¶·È‰È΋ ¯·Ú¿ 380 13,5 ¢ÚfiÌÔ˜ 308 10,9 ⁄·ÈıÚÔ˜ 145 5,1 ÕÏÏÔ˜ ¯ÒÚÔ˜ 567 20,1 ™‡ÓÔÏÔ 2820 100,0

∆¤ÏÔ˜, Ë Ù¤Ù·ÚÙË ÔÌ¿‰· (12,7%) ÂÚÈÏ·Ì‚¿ÓÂÈ ·Ù˘¯‹Ì·Ù· ̤۷ Î·È Á‡Úˆ ·fi ÙÔ Û¯ÔÏ›Ô, ÛÙÔ Û‡ÓÔÏfi ÙÔ˘˜ ÙÒÛÂȘ Ô˘ Û˘Ó¤‚ËÛ·Ó fiϘ ÙȘ ¿ÏϘ ÂÔ¯¤˜ ÂÎÙfi˜ ÙÔ˘ ηÏÔηÈÚÈÔ‡ Î·È Â›¯·Ó Â›Û˘ ÛÙÔ Û‡ÓÔÏfi ÙÔ˘˜ ˆ˜ Ì¿ÚÙ˘Ú˜ ¶·È‰È·ÙÚÈ΋ 2006;69:278-285

282

∞. ∞ÏÂÍfiÔ˘ÏÔ˜ Î·È Û˘Ó.

¶›Ó·Î·˜ 4. ∫·Ù·ÓÔÌ‹ ÙˆÓ 2820 ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ Û ٤ÛÛÂÚȘ ÔÌ¿‰Â˜ (ÈÂÚ·Ú¯È΋ Ù·ÍÈÓfiÌËÛË Î·Ù¿ Û˘ÛÙ¿‰Â˜), Ì ‚¿ÛË ‰ËÌÔÁÚ·ÊÈο Î·È ¿ÏÏ· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ Û˘Ì‚¿ÓÙÔ˜ ¶·Ú¿ÌÂÙÚÔ˜ ∏ÏÈΛ· 6-9 10-12 º‡ÏÔ ∞ÁfiÚÈ· ∫ÔÚ›ÙÛÈ· ∆fiÔ˜ ·Ù˘¯‹Ì·ÙÔ˜ ™›ÙÈ ™¯ÔÏÂ›Ô (̤۷ ‹ Á‡Úˆ) ¶·È‰È΋ ¯·Ú¿ ¢ÚfiÌÔ˜ ⁄·ÈıÚÔ˜ ÕÏÏÔ˜ ¯ÒÚÔ˜ ∆‡Ô˜ ·Ù˘¯‹Ì·ÙÔ˜ ¶ÙÒÛË ªÂÙ·ÊÔÚÈÎfi ̤ÛÔ ∞ȯÌËÚ¿ Î·È ‰ÈÂÈÛ‰˘ÙÈο ·ÓÙÈΛÌÂÓ· ∂ÎÚËÎÙÈÎfi ˘ÏÈÎfi ŒÁη˘Ì· ∏ÏÂÎÙÚÈÎfi Ú‡̷ ¢ËÏËÙËÚ›·ÛË (·fi Ê¿Ú̷η) ¢‹ÁÌ· ˙ÒÔ˘ ∂Ô¯‹ ·Ù˘¯‹Ì·ÙÔ˜ ÃÂÈÌÒÓ·˜ ÕÓÔÈÍË ∫·ÏÔη›ÚÈ ºıÈÓfiˆÚÔ ¶·ÚfiÓÙ˜ °ÔÓ›˜/Û˘ÁÁÂÓ›˜ ÕÏÏÔÈ

√Ì¿‰· 1Ë

2Ë

3Ë

4Ë

620 (42,7%) 416 (32,1%)

540 (37,2%) 545 (42,1%)

136 (9,4%) 143 (11,0%)

156 (10,7%) 192 (14,8%)

644 (37,7%) 392 (37,7%)

689 (40,3%) 396 (38,1%)

169 (9,9%) 110 (10,6%)

207 (12,1%) 141 (13,6%)

974 (98,5%) 0 (0,0%) 1 (0,3%) 0 (0,0%) 1 (0,8%) 60 (10,7%)

15 (1,5%) 59 (14,8%) 379 (99,7%) 9 (3,0%) 124 (99,2%) 499 (89,3%)

0 (0,0%) 2 (0,5%) 0 (0,0%) 277 (93,6%) 0 (0,0%) 0 (0,0%)

0 (0,0%) 338 (84,7%) 0 (0,0%) 10 (3,4%) 0 (0,0%) 0 (0,0%)

769 (41,7%) 17 (4,0%) 124 (47,3%) 4 (66,7%) 70 (93,3%) 8 (100,0%) 7 (100,0%) 36 (30,3%)

726 (39,4%) 136 (31,8%) 138 (52,7%) 2 (33,3%) 2 (2,7%) 0 (0,0%) 0 (0,0%) 81 (68,1%)

0 (0,0%) 275 (64,3%) 0 (0,0%) 0 (0,0%) 2 (2,7%) 0 (0,0%) 0 (0,0%) 2 (1,7%)

347 (18,8%) 0 (0,0%) 0 (0,0%) 0 (0,0%) 1 (1,3%) 0 (0,0%) 0 (0,0%) 0 (0,0%)

238 (36,1%) 318 (38,3%) 241 (38,1%) 239 (38,2%)

244 (37,9%) 283 (34,1%) 303 (47,9%) 255 (40,7%)

65 (9,9%) 91 (11,0%) 89 (14,1%) 34 (5,4%)

112 (17,0%) 138 (16,6%) 0 (0,0%) 98 (15,7%)

1035 (53,8%) 1 (0,1%)

644 (33,5%) 441 (53,5%)

244 (12,7%) 35 (4,2%)

0 (0,0%) 348 (42,2%)

Û˘ÌÌ·ıËÙ¤˜ ‹ Ê›ÏÔ˘˜ Î·È fi¯È ¿ÙÔÌ· ÙÔ˘ Û˘ÁÁÂÓÈÎÔ‡ ÂÚÈ‚¿ÏÏÔÓÙÔ˜. ™˘ÁÎÚ›ÓÔÓÙ·˜ Ù· ·Ù˘¯‹Ì·Ù· ·Ó¿ÌÂÛ· ÛÙ· ‰‡Ô ¤ÙË, ·Ú·ÙËÚÂ›Ù·È ·‡ÍËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙÔ˘˜ ÙÔ ¤ÙÔ˜ 2003 Û ÔÛÔÛÙfi 18% Û ۯ¤ÛË Ì ÙÔ 2000. ∏ ·‡ÍËÛË ·˘Ù‹ Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È Û˘Ó¿ÚÙËÛË Ù˘ ·‡ÍËÛ˘ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ Û˘Ì‚·›ÓÔ˘Ó Î˘Ú›ˆ˜ ÛÙÔ Û›ÙÈ (+28,8%) Î·È ÛÙÔÓ ‰ÚfiÌÔ (+46,4%). ¶·Ú·ÙËÚÂ›Ù·È Ù·˘Ùfi¯ÚÔÓ· ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ Û˘Ì‚·›ÓÔ˘Ó Ì¤Û· Î·È Á‡Úˆ ·fi ÙÔ Û¯ÔÏÂ›Ô (-25,3%), ηıÒ˜ Î·È ÛÙ·ÛÈÌfiÙËÙ· ÛÙË Û˘¯ÓfiÙËÙ· ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ Û˘Ì‚·›ÓÔ˘Ó Û ·È‰ÈΤ˜ ¯·Ú¤˜ ‹ ÛÙËÓ ‡·ÈıÚÔ. ŸÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ÂÓÙfiÈÛË ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜, ·Ú·ÙËÚÂ›Ù·È ·ÍÈÔÛËÌ›ˆÙË ·‡ÍËÛË ÙÔ˘ ÙÚ·˘Ì·ÙÈÛÌÔ‡ ÙˆÓ ¿ÎÚˆÓ ÙÔ 2003 (63,4%) Û ۯ¤ÛË Ì ٷ ·ÓÙ›ÛÙÔȯ· ÙÚ·‡Ì·Ù· ÙÔ˘ 2000 (36,9%), ÚÔÊ·ÓÒ˜ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ÚÔ·Ó·ÊÂÚıÂÈÛÒÓ ÙÒÛˆÓ. ∂›Û˘, ·Ú·ÙËÚÂ›Ù·È ·‡ÍËÛË ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ˘fi ÙËÓ Â›‚ÏÂ„Ë ¶·È‰È·ÙÚÈ΋ 2006;69:278-285

Û˘ÁÁÂÓÒÓ (fi¯È fï˜ ÁÔÓ¤ˆÓ) ·fi 4,3% Û 28,8% (x2: 327,9, p=0,000). ™ËÌÂÈÒÓÂÙ·È, Â›Û˘, Ë ·Ô˘Û›· ·Ù˘¯ËÌ¿ÙˆÓ ˘fi ÙËÓ Â›‚ÏÂ„Ë Ê‡Ï·Î· (baby sitter) ηٿ ÙÔ ¤ÙÔ˜ 2003, Û ·ÓÙ›ıÂÛË Ì ٷ 25 ·Ù˘¯‹Ì·Ù· (1,9% ÙÔ˘ ÂÙ‹ÛÈÔ˘ Û˘ÓfiÏÔ˘) ÙÔ˘ 2000. √È Û˘ÁÎÚ›ÛÂȘ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÂÙ·‚ÏËÙÒÓ ·Ó¿ÌÂÛ· ÛÙ· ‰‡Ô ʇϷ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ (‰ÔÎÈÌ·Û›· x2) ˆ˜ ÚÔ˜ ÙÔ Â›‰Ô˜ ÙÔ˘ ·Ù˘¯‹Ì·ÙÔ˜ (x2: 20,18, p=0,01) Î·È ÙË ı¤ÛË ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜ (x2: 34,58, p=0,00). ∆· ÎÔÚ›ÙÛÈ· ÚÔÛ‹Ïı·Ó ÛÙ· Â͈ÙÂÚÈο È·ÙÚ›· ÙÔ˘ ȉڇ̷ÙÔ˜ Ì ÌÂÁ·Ï‡ÙÂÚË Û˘¯ÓfiÙËÙ· ·fi fi,ÙÈ Ù· ·ÁfiÚÈ·, ÂÍ·ÈÙ›·˜ ·Ù˘¯‹Ì·ÙÔ˜ Ì ÂÌÏÔ΋ ÌÂÙ·ÊÔÚÈÎÔ‡ ̤ÛÔ˘ ηıÒ˜ Î·È ÂÁη˘Ì¿ÙˆÓ, ËÏÂÎÙÚÔÏËÍ›·˜ ‹ ‰ËÏËÙËÚ›·Û˘ ·fi ¯ËÌÈΤ˜ Ô˘Û›Â˜, ÂÓÒ Ù· ÙÚ·‡Ì·Ù¿ ÙÔ˘˜ ÂÓÙÔ›˙ÔÓÙ·Ó Î˘Ú›ˆ˜ ÛÙ· ¿ÎÚ·. ∞ÓÙ›ıÂÙ·, Ù· ·ÁfiÚÈ· ÂÌÊ¿ÓÈ˙·Ó ÌÂÁ·Ï‡ÙÂÚË Û˘¯ÓfiÙËÙ· ‰ËÁÌ¿ÙˆÓ ·fi ˙Ò·, ηıÒ˜ Î·È ÌÂÁ·Ï‡ÙÂÚË Û˘¯ÓfiÙËÙ· ÙÚ·˘Ì¿ÙˆÓ Ù˘ ÎÂÊ·Ï‹˜. ¢È·ÊÔÚ¿ ÛÙÔÓ

283

¶·È‰Èο ·Ù˘¯‹Ì·Ù· ÛÙËÓ fiÏË ÙˆÓ ¶·ÙÚÒÓ

·ÚÈıÌfi ÙˆÓ ÂÂÈÛÔ‰›ˆÓ ÛÙȘ ÙÒÛÂȘ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠ·Ó¿ÌÂÛ· ÛÙ· ‰‡Ô ʇϷ. √ ¤ÏÂÁ¯Ô˜ ÙˆÓ ÈÓ¿ÎˆÓ Û˘Ó¿ÊÂÈ·˜ ¤‰ÂÈÍ Â›Û˘ ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ˆ˜ ÚÔ˜ ÙËÓ Âԯȷ΋ ηٷÓÔÌ‹ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ·Ó¿ÌÂÛ· Û ·ÁfiÚÈ· Î·È ÎÔÚ›ÙÛÈ· (x2: 9,12, p=0,02), Ì ٷ ÚÒÙ· Ó· ÙÚ·˘Ì·Ù›˙ÔÓÙ·È Û˘¯ÓfiÙÂÚ· ηٿ ÙÔ˘˜ ηÏÔηÈÚÈÓÔ‡˜ Ì‹Ó˜ Û ۯ¤ÛË Ì ٷ ‰Â‡ÙÂÚ·.

™˘˙‹ÙËÛË ∏ ·Ó¿Ï˘ÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ηٷ‰ÂÈÎÓ‡ÂÈ ·‡ÍËÛË ÙˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ÙËÓ ÙÚÈÂÙ›· 2000-2003, fiˆ˜ Û˘Ó¿ÁÂÙ·È ·fi ÙËÓ ÚÔۤϢÛË ÛÙ· Â͈ÙÂÚÈο È·ÙÚ›· ÙÔ˘ ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶·ÙÚÒÓ. ∏ ·‡ÍËÛË ·˘Ù‹ ÔÊ›ÏÂÙ·È Î˘Ú›ˆ˜ ÛÙËÓ ·‡ÍËÛË ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ Û˘Ì‚·›ÓÔ˘Ó Ì¤Û· ÛÙÔ Û›ÙÈ, ηıÒ˜ Î·È Û ·‡ÍËÛË ÙˆÓ ÙÚÔ¯·›ˆÓ. ∞ÓÙ›ÛÙÔȯ·, ‰È·ÈÛÙÒıËΠ̛ˆÛË ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ Û˘Ì‚·›ÓÔ˘Ó Ì¤Û· ‹ Á‡Úˆ ·fi Ù· Û¯ÔÏ›· (·fi 17,8% Û 11,3%), ηıÒ˜ Î·È ÌÈÎÚ‹ ˘Ô¯ÒÚËÛË ·˘ÙÒÓ Ô˘ Û˘Ì‚·›ÓÔ˘Ó ÛÙȘ ·È‰ÈΤ˜ ¯·Ú¤˜ (·fi 14,8% Û 12,4%). ∂›Ó·È Èı·Ófi Ë ·Ú·ÙËÚÔ‡ÌÂÓË Ì›ˆÛË, Â¿Ó ‰ÂÓ ÔÊ›ÏÂÙ·È Û ÂӉ¯fiÌÂÓË ·ÓÂ¿ÚÎÂÈ· ‰Â‰ÔÌ¤ÓˆÓ ÙˆÓ ·Ú¯Â›ˆÓ ÙÔ˘ ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ, Ó· Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ÚÔÏËÙÈÎÒÓ Ì¤ÙÚˆÓ Ô˘ ¤¯Ô˘Ó ÏËÊı› Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÛÙË ¯ÒÚ· Ì·˜, fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· Ë Â¤ÎÙ·ÛË ÙÔ˘ ̤ÙÚÔ˘ ÙˆÓ Û¯ÔÏÈÎÒÓ ÙÚÔ¯ÔÓfiÌˆÓ ‹ Ê˘Ï¿ÎˆÓ, ηıÒ˜ Î·È Ë Â˘·ÈÛıËÙÔÔ›ËÛË ÙˆÓ ÂÎ·È‰Â˘ÙÈÎÒÓ Î·È ÙˆÓ ‰ËÌÔÙÈÎÒÓ ·Ú¯ÒÓ ˆ˜ ÚÔ˜ ÙËÓ ·ÛÊ¿ÏÂÈ· ÛÙ· Û¯ÔÏ›·. ŸÛÔÓ ·ÊÔÚ¿ ÛÙ· ·Ù˘¯‹Ì·Ù· Ô˘ Ï·Ì‚¿ÓÔ˘Ó ¯ÒÚ· ÛÙȘ ·È‰ÈΤ˜ ¯·Ú¤˜, ·Ú¿ ÙË ÌÈÎÚ‹ ÙÔ˘˜ Ì›ˆÛË, ·Ú·Ì¤ÓÔ˘Ó Û˘¯Ó¿ Î·È Ì¿ÏÈÛÙ· ÙÚÈÏ¿ÛÈ· ·fi ÙÔ 4,4% Ô˘ ¤¯ÂÈ ÂÎÙÈÌËı› ÁÈ· ÙÔ Û‡ÓÔÏÔ Ù˘ ¯ÒÚ·˜ (10). ∆·˘Ùfi¯ÚÔÓ·, Û ȉȷ›ÙÂÚ· ˘„ËÏ¿ Â›‰· ηٷÁÚ¿ÊÔÓÙ·È Ù· ÔÛÔÛÙ¿ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ÛÙÔ Û›ÙÈ ‹ fiÔ˘ ÂÌϤÎÔÓÙ·È ÌÂÙ·ÊÔÚÈο ̤۷, Ù· ÚÒÙ· ÂÍ·ÈÙ›·˜ Ù˘ Û˘¯ÓfiÙËÙ¿˜ ÙÔ˘˜ Î·È Ù· ‰Â‡ÙÂÚ· ÂÍ·ÈÙ›·˜ Ù˘ ‚·Ú‡ÙËÙ·˜ Î·È ÙˆÓ Û˘ÓÂÂÈÒÓ ÙÔ˘˜ (11). ™ÙËÓ ÚÒÙË ÂÚ›ÙˆÛË, ÂÎÙfi˜ ·fi ÙÔ˘˜ ·ÓÙÈÎÂÈÌÂÓÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÌϤÎÔÓÙ·È (12), ÛÙfi¯Ô˜ ÙˆÓ Ì¤ÙÚˆÓ ÚfiÏ˄˘ ı· Ú¤ÂÈ Ó· Â›Ó·È Î˘Ú›ˆ˜ Ë ÂÓË̤ڈÛË ÙˆÓ ÁÔÓ¤ˆÓ. ™ÙË ‰Â‡ÙÂÚË, fiÔ˘ ÂÌϤÎÂÙ·È Î˘Ú›ˆ˜ Ë ÔÏÈÙ›·, Â›Ó·È Û·Ê¤˜ fiÙÈ ı· Ú¤ÂÈ Ó· ˘ÈÔıÂÙËıÔ‡Ó Ï‹Úˆ˜ Ù· ηٿÏÏËÏ· ̤ÙÚ· ÁÈ· ÙËÓ ·ÛÊ¿ÏÂÈ· ÙˆÓ ·È‰ÈÒÓ, ›Ù ·˘Ù¿ Â›Ó·È ÂÈ‚¿Ù˜ (›Ûˆ οıÈÛÌ·, ˙ÒÓ˜ ·ÛÊ·Ï›-

·˜) (13) ›ÙÂ Â›Ó·È Ô‰ËÁÔ› Ô¯ËÌ¿ÙˆÓ (.¯. ÎÚ¿ÓË, ÚÔÛٷ٢ÙÈο ¿ÎÚˆÓ), ÂÓÒ ˘¿Ú¯Ô˘Ó Î·È ÂÚÈıÒÚÈ· ‚ÂÏÙ›ˆÛ˘ ÙˆÓ Û˘ÓıËÎÒÓ Û Â˙Ô‰ÚfiÌÈ· Î·È ‰ÚfiÌÔ˘˜ (14). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·Ú·ÙËÚ‹ıËΠÌÈ· ¿ÓÈÛË Î·Ù·ÓÔÌ‹ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ·Ó¿ÌÂÛ· ÛÙ· ‰‡Ô ʇϷ. ªÂ ‚¿ÛË Ù· ‰Â‰Ô̤ӷ Ô˘ ÂÍÂÙ¿ÛÙËηÓ, Ù· ·ÁfiÚÈ· Ê·›ÓÂÙ·È Ó· ÙÚ·˘Ì·Ù›˙ÔÓÙ·È Û˘¯ÓfiÙÂÚ· ·fi Ù· ÎÔÚ›ÙÛÈ· Û ·Ó·ÏÔÁ›· 1,6/1, Ë ÔÔ›· Â›Ó·È Û¯Â‰fiÓ Ù·˘ÙfiÛËÌË Ì ÂΛÓË Ô˘ ·Ó·Ê¤ÚÂÙ·È ·fi ¿ÏÏÔ˘˜ ÂÚ¢ÓËÙ¤˜ (15) ‹ ·fi Â›ÛË̘ ·Ó·ÊÔÚ¤˜ (16). ∏ ‰È·ÊÔÚ¿ ·˘Ù‹ Û ÌÂÁ¿ÏÔ ÔÛÔÛÙfi ÔÊ›ÏÂÙ·È ÛÙËÓ È‰ÈÔÛ˘ÁÎÚ·Û›·, ·ÏÏ¿ Î·È ÛÙÔÓ ÙÚfiÔ Î·È ÙÔ Â›‰Ô˜ ÂΉ‹ÏˆÛ˘ Ù˘ Û˘ÌÂÚÈÊÔÚ¿˜ ÙˆÓ ‰‡Ô Ê‡ÏˆÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ·È¯ÓȉÈÔ‡ ‹ ÙˆÓ ˘fiÏÔÈˆÓ ‰Ú·ÛÙËÚÈÔÙ‹ÙˆÓ ÙÔ˘˜. ¢È·ÊÔÚ¿ ‰È·ÈÛÙÒÓÂÙ·È, Â›Û˘, ˆ˜ ÚÔ˜ ÙË ı¤ÛË ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜, ÁÂÁÔÓfi˜ Ô˘ ¤¯ÂÈ ÛËÌ·Û›· ˆ˜ ÚÔ˜ ÙËÓ ÂΉ‹ÏˆÛË ÂӉ¯fiÌÂÓˆÓ ÂÈÏÔÎÒÓ. Ÿˆ˜ Ê¿ÓËΠ·fi ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·ÏÏ¿ Î·È ·fi ÚÔËÁÔ‡ÌÂÓ˜ ¤Ú¢Ó˜ (7) Ë Û˘¯ÓfiÙËÙ· ÙÚ·˘Ì·ÙÈÛÌÔ‡ ÛÙÔ ÎÂÊ¿ÏÈ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ÛÙ· ·ÁfiÚÈ· Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ· (22,1% Û ۯ¤ÛË Ì 16,6%) Î·È Ù· ÙÚ·‡Ì·Ù· ·˘Ù¿ ·ÎÔÏÔ˘ıÔ‡Ó Âԯȷ΋ ηٷÓÔÌ‹ Ì ·È¯Ì‹ (35,1% ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË) ηٿ ÙÔ˘˜ ·ÚÈÓÔ‡˜ Ì‹Ó˜ (17). ŸÛÔÓ ·ÊÔÚ¿ ÛÙ· ÎÔÈÓˆÓÈÎÔ-‰ËÌÔÁÚ·ÊÈο ¯·Ú·ÎÙËÚÈÛÙÈο, ·Ú·ÙËÚ‹ıËΠfiÙÈ Ù· ÂÚÈÛÛfiÙÂÚ· ·È‰È¿ ¤¯Ô˘Ó ÁÔÓ›˜ ¯·ÌËÏÔ‡ ‹ ̤ÙÚÈÔ˘ ÌÔÚʈÙÈÎÔ‡ ÂÈ¤‰Ô˘, ÌËÙ¤Ú˜ ÂÚÁ·˙fiÌÂÓ˜ Î·È ÙÔ˘Ï¿¯ÈÛÙÔÓ ¤Ó·Ó ·‰ÂÏÊfi ‹ ·‰ÂÏÊ‹ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ·. ∞ÓÙ›ÛÙÔȯ· ˘„ËÏ¿ ÔÛÔÛÙ¿ ¤¯Ô˘Ó ·Ú·ÙËÚËı› Î·È Û ¿ÏϘ ¤Ú¢Ó˜ ηٿ ÙÔ ·ÚÂÏıfiÓ (18-20). ¢ÂÓ Â›Ó·È fï˜ ÁÓˆÛÙfi ·Ó Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ·˘Ù¿ ·ÔÙÂÏÔ‡Ó ÚˆÙÔÁÂÓ›˜ ·Èٛ˜, ÔfiÙÂ Ô Û¯ÔÏÈ·ÛÌfi˜ Á›ÓÂÙ·È ¿ÓÙ· Ì ÂÈʇϷÍË. ∞fi Ù· ›‰Ë ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Ô˘ ÌÂÏÂÙ‹ıËηÓ, ÔÈ ÙÒÛÂȘ ·ÔÙÂÏÔ‡Ó ÙËÓ ÚÒÙË ·ÈÙ›· ÙÚ·˘Ì·ÙÈÛÌÔ‡ (66,7%) Î·È ·ÔÙÂÏÔ‡Ó ÙË ‰Â‡ÙÂÚË ·ÈÙ›· ı·Ó¿ÙÔ˘ ·fi ·Ù˘¯‹Ì·Ù· ÛÙ· ·È‰È¿ (11). ∏ ηٷÓÔÌ‹ ·˘ÙÒÓ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ Î·ıÒ˜ Î·È ÔÈ ·Èٛ˜ ÙÔ˘˜ ¤¯Ô˘Ó ··Û¯ÔÏ‹ÛÂÈ ÙÔ˘˜ ÂÚ¢ÓËÙ¤˜, fi¯È ÌfiÓÔ ‰ÈfiÙÈ ·ÔÙÂÏÔ‡Ó ÙÔÓ Î‡ÚÈÔ ÏfiÁÔ ÓÔÛËÏ›·˜ ÙˆÓ ·È‰ÈÒÓ, ·ÏÏ¿ Î·È ÁÈ·Ù› Û˘¯Ó¿ Â›Ó·È ÙÔ ·ÔÙ¤ÏÂÛÌ· Û˘ÁÎ·Ï˘Ì̤Ó˘ ‚›·˜ Ô˘ ·ÛÎÂ›Ù·È ÛÙ· ·È‰È¿ ·fi ÂÓ‹ÏÈΘ ‹ ¿ÏÏ· ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ (18). ∏ ηٷÓÔÌ‹ ÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ Û ÔÌ¿‰Â˜ ‚ÔËı¿ ÛÙË ‰È¿ÎÚÈÛË ÙˆÓ ÛÙfi¯ˆÓ ·Ú¤Ì‚·Û˘, ‰›ÓÔÓÙ·˜ ÙË ‰˘Ó·ÙfiÙËÙ· ÂÈΤÓÙÚˆÛ˘ ÛÙ· ηٿÏÏËÏ· ÁÈ· ÙËÓ Î¿ı ÂÚ›ÙˆÛË Ì¤ÙÚ· (ÂÎ·›‰Â˘ÛË, ÂÈÌfiÚʈÛË, ˘ÈÔı¤ÙËÛË ·ÙÔÌÈÎÒÓ ¶·È‰È·ÙÚÈ΋ 2006;69:278-285

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∞. ∞ÏÂÍfiÔ˘ÏÔ˜ Î·È Û˘Ó.

̤ÙÚˆÓ, ‚ÂÏÙ›ˆÛË ÙˆÓ Ì¤ÙÚˆÓ ·ÛÊ·Ï›·˜ ÙˆÓ ÂÛˆÙÂÚÈÎÒÓ Î·È Â͈ÙÂÚÈÎÒÓ ¯ÒÚˆÓ Î.¿.). ∆¤ÏÔ˜, Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ ÔÈ ÂÚÈÔÚÈÛÌÔ› Ô˘ Ù›ıÂÓÙ·È Û ·Ó¿ÏÔÁ˜ ÂÚÈÁÚ·ÊÈΤ˜ ÌÂϤÙ˜ Ô˘ ‚·Û›˙ÔÓÙ·È Û ·Ú¯Â›· ηٷÁÚ·ÊÒÓ, fiˆ˜ Î·È ÛÙËÓ ·ÚÔ‡Û·, Â›Ó·È ‰Â‰Ô̤ÓÔÈ Î·È Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔÓÙ·È ˘’ fi„ÈÓ ÚÈÓ ÁÂÓÈ΢ÙÔ‡Ó ÔÔÈ·‰‹ÔÙÂ Û˘ÌÂÚ¿ÛÌ·Ù·. ∏ ·Ô˘Û›· Ì·ÚÙ‡ÚˆÓ ÂÚÈÔÚ›˙ÂÈ ÙË ÛËÌ·ÓÙÈÎfiÙËÙ· ÙÔ˘ ¤ÏÂÁ¯Ô˘ Î·È ÂÈÛ¿ÁÂÈ Û‡Á¯˘ÛË ÛÙËÓ ·Ó¿Ï˘ÛË. ∞ÎfiÌË, ¤Ó· ¿ÏÏÔ Úfi‚ÏËÌ· Ù˘ ·ÚÔ‡Û·˜ ¤Ú¢ӷ˜ Â›Ó·È Ë ÂÎÙ›ÌËÛË ÙÔ˘ ηٿÏÏËÏÔ˘ ·ÚÔÓÔÌ·ÛÙ‹ ÁÈ· ÙÔÓ ˘ÔÏÔÁÈÛÌfi ÙˆÓ ‰ÂÈÎÙÒÓ Â›ÙˆÛ˘, ·ÊÔ‡ fiϘ ÔÈ ÂÚÈÙÒÛÂȘ ı· Ú¤ÂÈ Ó· ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙÔÓ ÏËı˘ÛÌfi ·˘Ù‹˜ Ù˘ ÙÈÌ‹˜. ∫¿ÙÈ Ù¤ÙÔÈÔ fï˜ ÚÔ¸Ôı¤ÙÂÈ ÂÈϤÔÓ ÛÙÔȯ›·, Ù· ÔÔ›· ‰ÂÓ ‹Ù·Ó ‰È·ı¤ÛÈÌ·. £ÂˆÚ‹ıËΠfiÙÈ ÚÔÛÂÁÁÈÛÙÈΤ˜ ÙÈ̤˜ Â›ÙˆÛ˘ ‚·ÛÈṲ̂Ó˜ Û ÂÏÏÈ‹ ÛÙÔȯ›·, Ì ÌÂÁ¿Ï· ‰È·ÛÙ‹Ì·Ù· ÂÌÈÛÙÔÛ‡Ó˘, ı· Ú¤ÂÈ Ó· ·ÔʇÁÔÓÙ·È Î·È ÁÈ· ÙÔÓ ÏfiÁÔ ·˘Ùfi ‰ÂÓ ¤ÁÈÓ ٤ÙÔÈ· ÂÎÙ›ÌËÛË. ¶ÚfiÛÊ·Ù· ÛÙÔȯ›· ‰Â›¯ÓÔ˘Ó fiÙÈ ÛÙËÓ ∂ÏÏ¿‰·, Ô ‰Â›ÎÙ˘ ı·Ó·ÙËÊfiÚˆÓ ·È‰ÈÎÒÓ ·Ù˘¯ËÌ¿ÙˆÓ ¤¯ÂÈ ‰È·ÌÔÚʈı› Û 7,8 ·È‰È¿ ÁÈ· οı 100.000 ηÙÔ›ÎÔ˘˜. ∞ÓÙ›ÛÙÔȯÔÈ ‰Â›ÎÙ˜ Â›Ó·È 0,27 ÁÈ· ÙȘ ÙÒÛÂȘ, 4,14 ÁÈ· Ù· ÙÚÔ¯·›· ‰˘ÛÙ˘¯‹Ì·Ù·, 0,14 ÁÈ· Ù· ÂÁη‡Ì·Ù· Î·È 0,15 ÁÈ· ÙȘ ‰ËÏËÙËÚÈ¿ÛÂȘ, Ô˘ Â›Ó·È ·fi ÙÔ˘˜ ˘„ËÏfiÙÂÚÔ˘˜ ÛÙËÓ ∂˘Úˆ·˚΋ ŒÓˆÛË (21). √È ·ÚÈıÌÔ› ·˘ÙÔ› ı· Ú¤ÂÈ Ó· ·ÔÙÂϤÛÔ˘Ó ·ÓÙÈΛÌÂÓÔ ÚÔ‚ÏËÌ·ÙÈÛÌÔ‡, ·ÏÏ¿ Ù·˘Ùfi¯ÚÔÓ· ηٷ‰ÂÈÎÓ‡Ô˘Ó fiÙÈ ˘¿Ú¯Ô˘Ó Î·È ÌÂÁ¿Ï· ÂÚÈıÒÚÈ· ‚ÂÏÙ›ˆÛ˘, Û˘ÁÎÚÈÓfiÌÂÓÔÈ Ì ·˘Ù¿ ¿ÏÏˆÓ ¯ˆÚÒÓ. ∏ ʇÛË ÙÔ˘ ·È‰ÈÎÔ‡ ·Ù˘¯‹Ì·ÙÔ˜ ‰‡ÛÎÔÏ· ÂÈÙÚ¤ÂÈ ÙËÓ ÂÍ·ÁˆÁ‹ ÂȉÈÎÒÓ Û˘ÌÂÚ·ÛÌ¿ÙˆÓ. ∞ÔÙÂÏ›, fï˜, ÁÂÓÈÎfiÙÂÚË ÂÔ›ıËÛË (22,23) fiÙÈ Û ÌÂÁ¿ÏÔ ‚·ıÌfi Ù· ·È‰Èο ·Ù˘¯‹Ì·Ù· ÌÔÚÔ‡Ó Ó· ÚÔ‚ÏÂÊıÔ‡Ó, Û¯ÂÙ›˙ÔÓÙ·È Ì ·Ú¿ÁÔÓÙ˜ ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ ÙˆÓ ·È‰ÈÒÓ ·Ó¿ÏÔÁÔ˘˜ Ì ·˘ÙÔ‡˜ Ô˘ ·ÚÔ˘ÛÈ¿ÛÙËÎ·Ó Î·È ÌÔÚÔ‡Ó Ó· ÂÚÈÔÚÈÛÙÔ‡Ó Ì ÙË Ï‹„Ë ÙˆÓ Î·Ù¿ÏÏËÏˆÓ Ì¤ÙÚˆÓ.

™˘ÌÂÚ¿ÛÌ·Ù· ∞fi ÙËÓ ÂÂÍÂÚÁ·Û›· ÙˆÓ ·Ú¯Â›ˆÓ ·Ù˘¯ËÌ¿ÙˆÓ ·È‰ÈÒÓ Û¯ÔÏÈ΋˜ ËÏÈΛ·˜ ÛÙËÓ fiÏË Ù˘ ¶¿ÙÚ·˜ ‰È·Ê·›ÓÂÙ·È fiÙÈ Ì›· ÛÂÈÚ¿ ·fi ·Ú¿ÁÔÓÙ˜ ·›˙Ô˘Ó Î¿ÔÈÔ ÚfiÏÔ, ÙfiÛÔ ÛÙË Û˘¯ÓfiÙËÙ· fiÛÔ Î·È ÛÙÔ Â›‰Ô˜ ÙˆÓ ·Ù˘¯ËÌ¿ÙˆÓ. √ÚÈṲ̂ÓÔÈ ·fi ·˘ÙÔ‡˜ ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜, ÙÔ˘˜ ¶·È‰È·ÙÚÈ΋ 2006;69:278-285

ÔÔ›Ô˘˜ ¤¯Ô˘Ó ÂÈÛËÌ¿ÓÂÈ Î·È ¿ÏÏÔÈ ÂÚ¢ÓËÙ¤˜, ›ӷÈ: ÙÔ Ê‡ÏÔ ÙÔ˘ ·È‰ÈÔ‡, Ë ËÏÈΛ· ÙÔ˘, ÙÔ ÌÔÚʈÙÈÎfi Â›Â‰Ô ÙˆÓ ÁÔÓ¤ˆÓ, Ë ··Û¯fiÏËÛË Ù˘ ÌËÙ¤Ú·˜ ‹ ·ÎfiÌË Î·È Ë ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Î·È Ë ÂÔ¯‹ ÙÔ˘ ·Ù˘¯‹Ì·ÙÔ˜. ¶ÂÚÈÁÚ·ÊÈΤ˜ ÌÂϤÙ˜, fiˆ˜ Ë Û˘ÁÎÂÎÚÈ̤ÓË, ÌÔÚÔ‡Ó Ó· ˘ԉ›ÍÔ˘Ó ·‰Ú¿ Ù¤ÙÔÈÔ˘ Ù‡Ô˘ ·Ú¿ÁÔÓÙ˜, ˘Ô‰ÂÈÎÓ‡ÔÓÙ·˜ Ù·˘Ùfi¯ÚÔÓ· Î·È ÙÔ˘˜ ÛÙfi¯Ô˘˜ Ô˘ ı· Ú¤ÂÈ Ó· ¤¯Ô˘Ó Ù· Ù˘¯fiÓ Ì¤ÙÚ· ÚfiÏ˄˘. øÛÙfiÛÔ, Ë ·ÔÛ·Ê‹ÓÈÛË ÙÔ˘ ÚfiÏÔ˘ ÙÔ˘˜, fiˆ˜ Î·È ÙÔ Â›Â‰Ô Û˘ÓÂÈÛÊÔÚ¿˜ ÙÔ˘ οı ·Ú¿ÁÔÓÙ· ÛÙÔ Û‡ÓıÂÙÔ ı¤Ì· Ô˘ ϤÁÂÙ·È ·È‰ÈÎfi ·Ù‡¯ËÌ·, ı· ÚÔ·„Ô˘Ó ÌfiÓÔ Ì¤Û· ·fi ÚÔÛÂÎÙÈο ۯ‰ȷṲ̂Ó˜ ÂȉËÌÈÔÏÔÁÈΤ˜ ¤Ú¢Ó˜, ÔÈ Ôԛ˜ Â›Ó·È ··Ú·›ÙËÙ˜.

∂˘¯·ÚÈÛٛ˜ ∂˘¯·ÚÈÛÙԇ̠ÙË ‰ÈÔ›ÎËÛË ÙÔ˘ “∫·Ú·Ì·Ó‰¿ÓÂÈÔ˘” ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ¶·ÙÚÒÓ ÁÈ· ÙË ‰È¿ıÂÛË ÙˆÓ ÛÙÔȯ›ˆÓ.

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6. Rivara FP. Pediatric injury control in 1999: where do we go from here? Pediatrics 1999;103:883-888.

7. §·Ú›Ô˘ ª™, ¢ÂÛ‡Ú˘ ¡, °ÂˆÚÁ·Î¿ÎÔ˘ Ã, ¶ÂÙÚ›‰Ô˘ ∂. ∫·Ù¿ÁÌ·Ù· ÎÚ·Ó›Ô˘ ·fi ·Ù˘¯‹Ì·Ù· Û ·È‰È¿: ÂȉËÌÈÔÏÔÁ›· Î·È ÚfiÏË„Ë. 13Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ∂ÏÏËÓÈ΋˜ ∂Ù·ÈÚ›·˜ ∫ÔÈÓˆÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶ÚÔ·ÁˆÁ‹˜ Ù˘ ÀÁ›·˜. ¶¿ÙÚ·: 1820 ª·˝Ô˘ 2001.

8. ªÔ˘ÛÙ¿ÎË ª, ¢ÂÛ‡Ú˘ ¡, ¶›ÙÛÔ˜ ¡, ¶ÂÙÚ›‰Ô˘ ∂. √È Î·ÎÒÛÂȘ ÙÔ˘ ÁfiÓ·ÙÔ˜ ÛÙ· ·È‰È¿ Û ‰Ú·ÛÙËÚÈfiÙËÙ˜ ÂχıÂÚÔ˘ ¯ÚfiÓÔ˘. 13Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ∂ÏÏËÓÈ΋˜ ∂Ù·ÈÚ›·˜ ∫ÔÈÓˆÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶ÚÔ·ÁˆÁ‹˜ Ù˘ ÀÁ›·˜. ¶¿ÙÚ·: 18-20 ª·˝Ô˘ 2001.

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9. ∫ÔÓÙ¤ µ, ¶ÂÙÚ›‰Ô˘ ∂. ¶·È‰Èο ·È¯Ó›‰È·, fiÛÔ ·ÛÊ·Ï‹ ›ӷÈ; 13Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ∂ÏÏËÓÈ΋˜ ∂Ù·ÈÚ›·˜ ∫ÔÈÓˆÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶ÚÔ·ÁˆÁ‹˜ Ù˘ ÀÁ›·˜. ¶¿ÙÚ·: 18-20 ª·˝Ô˘ 2001.

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Environmental Burden of Disease Series No. 8, 2004. http://www.who.int/entity/quantifying_ehimpacts/ publications/en/ebd8web.pdf 12. Belechri M, Petridou E, Trichopoulos D. Bunk versus conventional beds: a comparative assessment of fall injury risk. J. Epidemiol Community Health 2002;56:413-417.

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ORIGINAL ARTICLE

∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÊÔÚ¤ˆÓ Ù˘ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÂÈÓÂÊÚȉ›ˆÓ ÛÙËÓ ∂ÏÏ¿‰· Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÌÔÚÈ·ÎÒÓ Ù¯ÓÈÎÒÓ ªÔÓ¿‰· ∂Ó‰ÔÎÚÈÓÔÏÔÁ›·˜ªÂÙ·‚ÔÏÈÛÌÔ‡ A’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·” AÏÏËÏÔÁÚ·Ê›·: ∞ÓÙˆÓ›· ¢·ÛÙ·Ì¿ÓË ∫·ÏÏÈÁ¿ 5 ∆.∫. 152 37, ºÈÏÔı¤Ë ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 19-05-2006 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 24-05-2006

∞. ¢·ÛÙ·Ì¿ÓË, ª. ¢Ú·ÎÔÔ‡ÏÔ˘, ∞. ™ÂÚÙ‰¿ÎË, °.¶. ÃÚÔ‡ÛÔ˜, ∞. ¢¿ÎÔ˘ - µÔ˘ÙÂÙ¿ÎË

¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: ∏ ‰È·Ù·Ú·¯‹ Ù˘ ÛÙÂÚÂÔÂȉÔÁ¤ÓÂÛ˘ Ô˘ ÚÔηÏÂ›Ù·È ·fi ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓȉ›Ô˘

Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ (CYP21), ·ÔÙÂÏ› ÙÔ Û˘¯ÓfiÙÂÚÔ ·›ÙÈÔ Ù˘ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÂÈÓÂÊÚȉ›ˆÓ (™À∂). ¢Â‰Ô̤ӷ ÁÈ· ÙË Û˘¯ÓfiÙËÙ· ÙÔ˘ ÁÔÓȉ›Ô˘, ‚·ÛÈṲ̂ӷ Û ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜, Â›Ó·È ÂÏ¿¯ÈÛÙ·. ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ë ·Ó·˙‹ÙËÛË ÙÔ˘ ›‰Ô˘˜ Î·È Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi. ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ¢Â›ÁÌ·Ù· ·›Ì·ÙÔ˜ ÓÂÔÁÓÒÓ ÂÏ‹ÊıËÛ·Ó ·fi Ì·ÈÂ˘Ù‹ÚÈ· fiÏ˘ Ù˘ ¯ÒÚ·˜. ∏ ·Ó¿Ï˘ÛË ÙÔ˘ DNA ¤ÁÈÓ Û 381 ‰Â›ÁÌ·Ù· (762 ·ÏÏËÏfiÌÔÚÊ·). ∏ ̤ıÔ‰Ô˜ ÙÔ˘ ÂÎÏÂÎÙÈÎÔ‡ ÔÏÏ·Ï·ÛÈ·ÛÌÔ‡ ÙÌ‹Ì·ÙÔ˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ·ÏÏËÏfiÌÔÚÊÔ˘ (allele specific PCR) ÂÊ·ÚÌfiÛÙËΠÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË 12 ÌÔÚÈ·ÎÒÓ ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21: ÔÌfi˙˘ÁÔ˜ ·¿ÏÂÈ„Ë/ÌÂÙ·ÙÚÔ‹ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21, P30L Î·È W22X (ÂÍÒÓÈÔ 1), I2splice (ÈÓÙÚfiÓÈÔ 2), 8bpdelE3 (ÂÍÒÓÈÔ 3), I172N (ÂÍÒÓÈÔ 4), ClusterE6 (ÂÍÒÓÈÔ 6), V281L Î·È F306+T (ÂÍÒÓÈÔ 7), Q318X Î·È R356W (ÂÍÒÓÈÔ 8), P453S (ÂÍÒÓÈÔ 10). ∂ÓÓ¤· ·fi ·˘Ù¤˜ ÙȘ ÌÂÙ·ÏÏ¿ÍÂȘ ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ 94% ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 Û ÏËı˘ÛÌfi ∂ÏÏ‹ÓˆÓ ·Û¯fiÓÙˆÓ, Û‡Ìʈӷ Ì ·Ï·ÈfiÙÂÚË ÌÂϤÙË. ∞ÔÙÂϤÛÌ·Ù·: ∞ÓȯÓ‡ıËÎ·Ó ÌÂÙ·ÏÏ¿ÍÂȘ Û 39 ·ÏÏËÏfiÌÔÚÊ· (5,12%): ‰ÂηÙÚ›· Ù˘ ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Ù˘ ™À∂ (Q318X, 1,3%; I172N, 0,14%; I2splice, 0,14%, W22X, 0,14%) Î·È 26 Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ (V281L, 3,28%; P453S, 0,98%; P30L, 0,28%). ¶ÔÛÔÛÙfi 10,2% ÙÔ˘ ‰Â›ÁÌ·ÙÔ˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‹Ù·Ó ÊÔÚ›˜ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘. ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘ ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Ù˘ ÓfiÛÔ˘ Â›Ó·È 3,4% Î·È Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ 6,8%. ÀÔÏÔÁ›ÛÙËÎÂ Ë Û˘¯ÓfiÙËÙ· Ù˘ ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ Û 1:3.436 Î·È Ë Û˘¯ÓfiÙËÙ· Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Û 1:859. ∏ ˘ÔÏÔÁÈÛı›۷ Û˘¯ÓfiÙËÙ· ÙÔ˘ ÁÔÓȉ›Ô˘ Â›Ó·È 0,051. ™˘ÌÂÚ¿ÛÌ·Ù·: ∏ Û˘¯ÓfiÙËÙ· Ù˘ ÓfiÛÔ˘ Î·È ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Â›Ó·È Ôχ ÌÂÁ·Ï‡ÙÂÚË ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi ¤Ó·ÓÙÈ ÙˆÓ ∫ÈÓ¤˙ˆÓ Î·È ÙˆÓ ¡ÂÔ˙ËÏ·Ó‰ÒÓ, ÔÈ ÔÔ›ÔÈ ¤¯Ô˘Ó Ú·ÁÌ·ÙÔÔÈ‹ÛÂÈ ÌÂϤÙ˜ Ì ·Ó¿ÏÔÁ˜ ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜. ∏ ·ÚÔ‡Û· ¤Ú¢ӷ ÂȂ‚·›ˆÛ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÚÔËÁÔ‡ÌÂÓ· ‰Â‰Ô̤ӷ ÂϤÁ¯ˆÓ ‰È·ÏÔÁ‹˜ ÓÂÔÁÓÒÓ (screening), ‚·ÛÈṲ̂ӷ Û ÔÚÌÔÓÈΤ˜ ÂÍÂÙ¿ÛÂȘ, ˘ÔÂÎÙÈÌÔ‡Ó ÙË Û˘¯ÓfiÙËÙ· Ù˘ ™À∂. ∂ÈϤÔÓ, ÚÔ·ÙÂÈ ÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Ë Û˘¯ÓfiÙËÙ· ÙÔ˘ ÁÔÓȉ›Ô˘ ÔÈΛÏÏÂÈ ÛËÌ·ÓÙÈο ÛÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÏËı˘ÛÌÔ‡˜ Î·È ‰ÂÓ ÌÔÚ› Ó· ˘ÔÏÔÁÈÛÙ› ˘ÔıÂÙÈο ·fi ‰Â‰Ô̤ӷ ¿ÏÏˆÓ ÏËı˘ÛÌÈ·ÎÒÓ ÔÌ¿‰ˆÓ. √ ηıÔÚÈÛÌfi˜ ÙÔ˘ ›‰Ô˘˜ Î·È Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÙÔ˘ CYP21 ÁÔÓȉ›Ô˘ fiˆ˜ ·ÚÔ˘ÛÈ¿ÛÙËηÓ, Â›Ó·È È‰È·›ÙÂÚ· ¯Ú‹ÛÈÌÔ˜: ·) ÁÈ· ÙËÓ ·Ó·˙‹ÙËÛË ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘ ÓfiÛÔ˘ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi Î·È ÙË ¯ÔÚ‹ÁËÛË ÁÂÓÂÙÈÎÒÓ Û˘Ì‚Ô˘ÏÒÓ, ‚) ÁÈ· ÙËÓ ¤ÁηÈÚË ·Ó·ÁÓÒÚÈÛË ÙˆÓ ‡ÔÙˆÓ ÁÈ· ÙË ‰È·Ù·Ú·¯‹ ÂÌ‚Ú‡ˆÓ ηٿ ÙÔÓ ÚÔÁÂÓÓËÙÈÎfi ¤ÏÂÁ¯Ô Î·È Á) ÁÈ· ÙË ‰ËÌÈÔ˘ÚÁ›· ‚¿Û˘ ‰Â‰ÔÌ¤ÓˆÓ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂÊ·ÚÌÔÛÙ› ÚfiÁÚ·ÌÌ· screening ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi.

§¤ÍÂȘ ÎÏÂȉȿ: ™˘ÁÁÂÓ‹˜ ˘ÂÚÏ·Û›· ÂÈÓÂÊÚȉ›ˆÓ, 21-˘‰ÚÔÍ˘Ï¿ÛË, ÌÂÙ·ÏÏ¿ÍÂȘ, Û˘¯ÓfiÙËÙ· ÂÙÂÚÔ˙˘ÁˆÙÒÓ

Detection of congenital adrenal hyperplasia carrier frequency in Greece by molecular methods Department of Endocrinology-Metabolism, 1st Pediatric Clinic, University of Athens, “Agia Sofia” Children’s Hospital

A. Dastamani, M. Dracopoulou, A. Sertedaki, G.P. Chroussos, A. Dakou - Voutetakis

Abstract Background: Defective steroidogenesis caused by mutations of the 21-hydroxylase gene (CYP21), is the most common cause of congenital adrenal hyperplasia (CAH), covering about 95% of cases of CAH. ∏ ÂÚÁ·Û›· ·˘Ù‹ ‚Ú·‚‡ıËΠ̠ÙÔ ÃˆÚ¤ÌÂÈÔ Œ·ıÏÔ ÛÙÔ 43Ô ¶·ÓÂÏÏ‹ÓÈÔ ¶·È‰È·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ, ∫ˆ˜ 17 πÔ˘Ó›Ô˘ 2005

¶·È‰È·ÙÚÈ΋ 2006;69:286-293

287

™˘¯ÓfiÙËÙ· ÙˆÓ ÊÔÚ¤ˆÓ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÂÈÓÂÊÚȉ›ˆÓ

Data on the gene frequency based on molecular studies are scarce. The aim of this study was to determine the nature of CYP21 gene defects, their frequencies and their geographic distribution in the Hellenic population, which are of theoretical and practical importance for genetic counseling.

Methods: Blood samples from unrelated neonates were obtained from maternity hospitals around Greece. DNA analysis was carried out on 762 chromosomes. Allele-specific PCR was employed to identify 12 molecular defects of the CYP21 gene: homozygous deletion/conversion, P30L and W22X (exon 1), I2splice (intron 2), 8bpdE3 (exon 3), I172N (exon 4), ClusterE6 (exon 6), V281L and F306+T (exon 7), Q318X and R356W (exon 8), P453S (exon 10). It had previously been shown that these mutations account for 94% of CYP21 defects in the Greek patient population.

Results: Thirty-nine mutant alleles (5.12%) were detected, all in the heterozygous state. Thirteen mutant alleles (1.7%) carried mutations associated with the classical (C) form of 21-hydroxylase deficiency; 10 Q318X (1.3%), 1 I172N (0.14%), 1 π2splice (0.14%), 1 W22X (0.14%). Twenty-six mutant alleles (3.28%) carried mutations concordant with the non-classical (NC) form of the disease; 17 V281L (2.23%), 7 P453S (0.98%) and 2 P30L (0.28%). In this study, 10.2% of the subjects were found to be carriers of molecular defects of 21-hydroxylase deficiency. The heterozygote frequency for C form was 3.4% and for NC forms 6.8%. It was estimated in the Hellenic population the incidence of the NC form is 1:859 and of the C form 1:3,436. The calculated gene frequency is 0.051.

Conclusions: The carrier frequency is higher in Greek population than in Chinese and New Zealand populations who also underwent direct genetic testing of the CYP21 gene. It was confirmed that previous findings based on hormonal newborn screening appear inaccurate and underestimate the frequency of CAH. Gene frequency varies significantly in different populations and cannot be extrapolated from the data of some population groups only. The findings of this study can be applied: a) to detect heterozygotes in the general population, a prerequisite for genetic counseling, b) for early recognition of the affected fetus during prenatal testing, important for prevention of virilization of the female fetus, and c) to create a data base for establishing a neonatal screening programme in the Greek population.

Correspondence: Antonia Dastamani 5, ∫alliga Str. 152 37, Filothei Date of submission: 19-05-2006 Date of approval: 24-05-2006

Key words: Congenital adrenal hyperplasia, 21-hydroxylase, mutations, carrier frequency.

∂ÈÛ·ÁˆÁ‹ ∏ Û˘ÁÁÂÓ‹˜ ˘ÂÚÏ·Û›· ÂÈÓÂÊÚȉ›ˆÓ (™À∂) ·ÔÙÂÏ› ÎÏËÚÔÓÔÌÈ΋ ‰È·Ù·Ú·¯‹ Ù˘ ÂÈÓÂÊÚȉȷ΋˜ ÛÙÂÚÂÔÂȉÔÁ¤ÓÂÛ˘, Ô˘ ÔÊ›ÏÂÙ·È Û ·ÓÂ¿ÚÎÂÈ· ÂÓfi˜ ·fi Ù· 5 ¤Ó˙˘Ì· Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙË Û‡ÓıÂÛË Ù˘ ÎÔÚÙÈ˙fiÏ˘ ·fi ¯ÔÏËÛÙÂÚfiÏË. ¶ÂÚ·ÈÙ¤Úˆ ı· Á›ÓÂÈ ·Ó·ÊÔÚ¿ ÛÙËÓ ·ÓÂ¿ÚÎÂÈ· Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘, ·ÊÔ‡ Ë ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÂÚÈÙÒÛÂˆÓ ™À∂ (90-95%) ÚÔηÏÂ›Ù·È ·fi ·ÓÂ¿ÚÎÂÈ· Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘, ÂÓfi˜ ÌÈÎÚÔÛˆÌÈ·ÎÔ‡ ΢ÙÔ¯ÚÒÌ·ÙÔ˜ ƒ450, Ô˘ ηٷχÂÈ ÙËÓ ·ÓÙ›‰Ú·ÛË ÌÂÙ·ÙÚÔ‹˜ Ù˘ 17-√∏ ÚÔÁÂÛÙÂÚfiÓ˘ (17√∏P) Û 11-‰ÂÔ͢ÎÔÚÙÈ˙fiÏË. ∏ ÂÓ˙˘ÌÈ΋ ·˘Ù‹ ‰È·Ù·Ú·¯‹, ˆ˜ ·Ó·Ì¤ÓÂÙ·È, ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË ÌÂȈ̤ÓË ·Ú·ÁˆÁ‹ ÎÔÚÙÈ˙fiÏ˘, Ë ÔÔ›· Ô‰ËÁ› - ̤ۈ ÙÔ˘ Ì˯·ÓÈÛÌÔ‡ ·ÚÓËÙÈ΋˜ ·Ï›Ó‰ÚÔÌ˘ Ú‡ıÌÈÛ˘ - Û ˘ÂÚ¤ÎÎÚÈÛË ÎÔÚÙÈÎÔÙÚÔ›Ó˘ (∞C∆∏). ∏ ˘ÂÚ¤ÎÎÚÈÛË ∞C∆∏ ÚÔηÏ› ˘ÂÚÏ·Û›· Î·È ˘ÂÚÏÂÈ-

ÙÔ˘ÚÁ›· ÙˆÓ ÂÈÓÂÊÚȉ›ˆÓ. √È Úfi‰ÚÔ̘ Ô˘Û›Â˜ Ô˘ ·ıÚÔ›˙ÔÓÙ·È, ÏfiÁˆ ÙÔ˘ ˘¿Ú¯ÔÓÙÔ˜ ÂÓ˙˘ÌÈÎÔ‡ ÊÚ·ÁÌÔ‡, ÚÔˆıÔ‡ÓÙ·È ÚÔ˜ ·Ú·ÁˆÁ‹ ·Ó‰ÚÔÁfiÓˆÓ (∂ÈÎfiÓ· 1). ø˜ ÂÎ ÙÔ‡ÙÔ˘, ˘¿Ú¯ÂÈ ‰ÈÙÙ‹ ÔÚÌÔÓÈ΋ ·Ú¤ÎÎÏÈÛË: ·ÓÂ¿ÚÎÂÈ· ÎÔÚÙÈ˙fiÏ˘ Î·È ˘ÂÚ·Ó‰ÚÔÁÔÓ·ÈÌ›· (1). √ ‚·ıÌfi˜ Ù˘ ÂÓ˙˘ÌÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ ηıÔÚ›˙ÂÈ ÙË ‚·Ú‡ÙËÙ· Ù˘ ÎÏÈÓÈ΋˜ ¤ÎÊÚ·Û˘ Ù˘ ™À∂. ¶Ï‹Ú˘ ·ÒÏÂÈ· Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ Ô‰ËÁ› Û ‚·ÚÈ¿ ÎÏÈÓÈ΋ ÂÈÎfiÓ· (ÎÏ·ÛÈ΋ ÌÔÚÊ‹), ÂÓÒ Ë ÌÂÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ¤¯ÂÈ ËÈfiÙÂÚË ÎÏÈÓÈ΋ ¤ÎÊÚ·ÛË (ÌË ÎÏ·ÛÈ΋ ÌÔÚÊ‹). ∏ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ Ù·ÍÈÓÔÌÂ›Ù·È ÛÙȘ ·ÎfiÏÔ˘ı˜ ‰‡Ô ˘ÔÔÌ¿‰Â˜: ·) ªÔÚÊ‹ Ì ·ÒÏÂÈ· ¿Ï·ÙÔ˜ (salt wastingSW). ∞ÔÙÂÏ› ‚·ÚÈ¿ ÂÓ˙˘ÌÈ΋ ‰È·Ù·Ú·¯‹ Ô˘ ÂΉËÏÒÓÂÙ·È ÛÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· Ì ·ÚÚÂÓÔÔ›ËÛË ÙˆÓ ¤Íˆ ÁÂÓÓËÙÈÎÒÓ ÔÚÁ¿ÓˆÓ ÛÙ· ı‹Ï· Î·È Ê·ÈÓfiÌÂÓ· ·ÓÂ¿ÚÎÂÈ·˜ ÎÔÚÙÈ˙fiÏ˘ Î·È ·Ï‰ÔÛÙÂÚfiÓ˘ Î·È ÛÙ· ‰‡Ô ʇϷ. ∂¿Ó ‰ÂÓ ¶·È‰È·ÙÚÈ΋ 2006;69:286-293

288

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18-OH-ÎÔÚÙÈÎÔÛÙÂÚfiÓË (18-ÔÍÂȉ¿ÛË) ƒ-450c11 ∞ωÔÛÙÂÚfiÓË

∂ÈÎfiÓ· 1. µÈÔÛ‡ÓıÂÛË ÛÙÂÚÔÂȉÒÓ.

‰È·ÁÓˆÛÙ› ¤ÁηÈÚ·, Ô‰ËÁ› Û ·Ê˘‰¿ÙˆÛË, ÔͤˆÛË, Ô˘Ú·ÈÌ›·, ηٷÏËÍ›· Î·È ÙÂÏÈο Û ı¿Ó·ÙÔ ÙȘ ÚÒÙ˜ ‚‰ÔÌ¿‰Â˜ Ù˘ ˙ˆ‹˜. ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜, Ù· ÌÂÓ ı‹Ï· ÎÈÓ‰˘ÓÂ‡Ô˘Ó Ó· ¯·Ú·ÎÙËÚÈÛÙÔ‡Ó ˆ˜ ¿ÚÚÂÓ· ηٿ ÙË Á¤ÓÓËÛË, ÂÓÒ ÙfiÛÔ Ù· ·ÁfiÚÈ· fiÛÔ Î·È Ù· ÎÔÚ›ÙÛÈ· ÎÈÓ‰˘ÓÂ‡Ô˘Ó ·fi ·ÈÊÓ›‰ÈÔ ı¿Ó·ÙÔ (1). ‚) ªÔÚÊ‹ Ì ·Ï‹ ·ÚÚÂÓÔÔ›ËÛË (simple virilizing - SV). ™ÙË ÌÔÚÊ‹ ·˘Ù‹ ‰È·ÈÛÙÒÓÂÙ·È ÔÈΛÏÔ˘ ‚·ıÌÔ‡ ·ÚÚÂÓÔÔ›ËÛË ÙˆÓ ıËϤˆÓ Î·È ÚÒÈÌË ‹‚Ë, Ì ÂÈÙ¿¯˘ÓÛË ÙfiÛÔ Ù˘ ۈ̷ÙÈ΋˜ ·Ó¿Ù˘Í˘ fiÛÔ Î·È Ù˘ ÛÎÂÏÂÙÈ΋˜ ˆÚ›Ì·ÓÛ˘ Î·È ÛÙ· ‰‡Ô ʇϷ, ÂÓÒ ‰ÂÓ ·Ú·ÙËÚÔ‡ÓÙ·È ËÏÂÎÙÚÔÏ˘ÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ (1). ∏ ÌË ÎÏ·ÛÈ΋ ÌÔÚÊ‹ (non classical - NC) Ù˘ ™À∂ ¤¯ÂÈ ÔÈΛÏË ÎÏÈÓÈ΋ ¤ÎÊÚ·ÛË Î·È ÂÚÈÏ·Ì‚¿ÓÂÈ ÚÒÈÌË ÙÚ›¯ˆÛË ÙÔ˘ ÂÊË‚·›Ô˘, ˘ÂÚÙÚ›¯ˆÛË, ·ÎÌ‹ Î·È ‰È·Ù·Ú·¯¤˜ Ù˘ ÂÌÌ‹ÓÔ˘ Ú‡Ûˆ˜ Î·È Ù˘ ÁÔÓÈÌfiÙËÙ·˜ (1). ∏ ™À∂ ÌÂÙ·‚È‚¿˙ÂÙ·È Ì ˘ÔÏÂÈfiÌÂÓÔ ÛˆÌ·ÙÈÎfi ¯·Ú·ÎÙ‹Ú·. ∏ Û˘¯ÓfiÙËÙ· Ù˘ ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ ÔÈΛÏÂÈ ÛÙȘ ‰È¿ÊÔÚ˜ ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜ ·fi 1:10.000 ¤ˆ˜ 1:18.000 (1). ∏ Û˘¯ÓfiÙËÙ· Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Î˘Ì·›ÓÂÙ·È ·fi 1:100 ¤ˆ˜ 1:1.000, ·Ó¿ÏÔÁ· Ì ÙËÓ ÏËı˘ÛÌȷ΋ ÔÌ¿‰· (2). ∏ ÌË ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ™À∂ ·ÔÙÂÏ› ÙÔ Û˘¯ÓfiÙÂÚÔ, ÁÂÓÂÙÈÎÒ˜ ¶·È‰È·ÙÚÈ΋ 2006;69:286-293

ηıÔÚÈ˙fiÌÂÓÔ, ÌÂÙ·‚ÔÏÈÎfi ÓfiÛËÌ· ÛÙÔÓ ¿ÓıÚˆÔ (3). ∆Ô ¤Ó˙˘ÌÔ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ Â›Ó·È ¤Ó· ÌÈÎÚÔÛˆÌÈ·Îfi ΢Ùfi¯ÚˆÌ· ƒ450 (ƒ450c21), Ô˘ Έ‰ÈÎÔÔÈÂ›Ù·È ·fi ÙÔ ÁÔÓ›‰ÈÔ CYP21 (1). ∆Ô ÁÔÓ›‰ÈÔ ·˘Ùfi ‰ڿ˙ÂÙ·È ÛÙÔ ‚Ú·¯‡ ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 6 (6p21,3) Î·È Û ÁÂÈÙÓ›·ÛË Ì ٷ ÁÔÓ›‰È· ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜, ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ Ì›˙ÔÓÔ˜ Û˘ÛÙ‹Ì·ÙÔ˜ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜. ™Â ·fiÛÙ·ÛË 30kb ·fi ÙÔ ÁÔÓ›‰ÈÔ ·˘Ùfi ÂÓÙÔ›˙ÂÙ·È ÙÔ „¢‰ÔÁÔÓ›‰ÈÔ (CYP21ƒ). ∆· ‰‡Ô ·˘Ù¿ ÁÔÓ›‰È· ¤¯Ô˘Ó Ì‹ÎÔ˜ 3kb ÙÔ Î·ı¤Ó·. ¶·Ú¿ ÙËÓ ˘„ËÏ‹ ÔÌÔÏÔÁ›· ÙˆÓ ‰‡Ô ·˘ÙÒÓ ÁÔÓȉ›ˆÓ (98%), ÙÔ „¢‰ÔÁÔÓ›‰ÈÔ Â›Ó·È ÙÂÏ›ˆ˜ ·ÓÂÓÂÚÁfi. √È ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ Ô‰ËÁÔ‡Ó Û ·ÓÂ·Ú΋ ·Ú·ÁˆÁ‹ ÙÔ˘ ÂÓ˙‡ÌÔ˘ 21-˘‰ÚÔÍ˘Ï¿ÛË Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ‰‡Ô Ù‡ˆÓ ·Ó·Û˘Ó‰˘·ÛÌÒÓ ÌÂٷ͇ ÙˆÓ ‰‡Ô ·˘ÙÒÓ ÁÔÓȉ›ˆÓ (CYP21-CYP21P): ·) ¿ÓÈÛÔ˜ ÂȯȷÛÌfi˜ ηٿ ÙË Ì›ˆÛË, Ô˘ Ô‰ËÁ› Û Ï‹ÚË ·¿ÏÂÈ„Ë ÙÔ˘ CYP21 (deletion) Î·È ‚) Ê·ÈÓfiÌÂÓ· ÌÂÙ·ÙÚÔ‹˜ (conversion) Ô˘ ÚÔηÏÔ‡Ó ÙË ÌÂÙ·ÊÔÚ¿ ·ÓÂÓÂÚÁÒÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ·fi ÙÔ CYP21P ÛÙÔ CYP21, fiÔ˘ ηı›ÛÙ·ÓÙ·È ÊıÔÚÔÔȤ˜ (1). √È ÁÓˆÛÙ¤˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 Ô˘ Ô‰ËÁÔ‡Ó ÛÙȘ ‰È¿ÊÔÚ˜ ÌÔÚʤ˜ Ù˘ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ Â›Ó·È ··Ï›„ÂȘ/

™˘¯ÓfiÙËÙ· ÙˆÓ ÊÔÚ¤ˆÓ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÂÈÓÂÊÚȉ›ˆÓ

ÌÂÙ·ÙÚÔ¤˜ Î·È ÂÚÈÛÛfiÙÂÚ˜ ·fi 50 ÛËÌÂȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ (·ÚÂÚÌËÓ‡ÛÈ̘, ·ÓÂÚÌËÓ‡ÛÈ̘, ÌÂÙ¿ıÂÛ˘ Ï·ÈÛ›Ô˘ ·Ó¿ÁÓˆÛ˘). ∞·Ï›„ÂȘ/ÌÂÙ·ÙÚÔ¤˜ Î·È ÂÓÓ¤· ÛËÌÂȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó ÙÔ 95% (4) ÙˆÓ ÌÔÚÈ·ÎÒÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ ·ÁÎÔÛÌ›ˆ˜. ∞·Ï›„ÂȘ/ÌÂÙ·ÙÚÔ¤˜ Î·È ÂÓÓ¤·, ‰È·ÊÔÚÂÙÈΤ˜ fï˜, ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ 94% ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ Û ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi ·Û¯fiÓÙˆÓ, Û‡Ìʈӷ Ì ÚÔËÁÔ‡ÌÂÓË ÌÂϤÙË ÙÔ˘ ÂÚÁ·ÛÙËÚ›Ô˘ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ (5). ∏ ‚·Ú‡ÙËÙ· Ù˘ ÎÏÈÓÈ΋˜ ¤ÎÊÚ·Û˘ (Ê·ÈÓfiÙ˘Ô˜) ηıÔÚ›˙ÂÙ·È Î˘Ú›ˆ˜ ·fi ÙÔ Â›‰Ô˜ ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ (ÁÔÓfiÙ˘Ô˜), ÂÓÒ Û ÂÚÈÙÒÛÂȘ Û‡ÓıÂÙÔ˘ ÂÙÂÚÔ˙˘ÁÒÙË (compound heterozygote), Ô Ê·ÈÓfiÙ˘Ô˜ ηıÔÚ›˙ÂÙ·È ·fi ÙË ÌÂÙ¿ÏÏ·ÍË Ô˘ ÚÔηÏ› ÙË ÌÈÎÚfiÙÂÚË ÂÓ˙˘ÌÈ΋ ‰È·Ù·Ú·¯‹ (1). ø˜ ÂÎ ÙÔ‡ÙÔ˘, Ô Î·ıÔÚÈÛÌfi˜ ÙÔ˘ ÁÔÓÔÙ‡Ô˘ Â›Ó·È ¯Ú‹ÛÈÌÔ˜ ÁÈ· ÙËÓ Úfi‚ÏÂ„Ë ÙˆÓ ÎÏÈÓÈÎÒÓ ÂΉËÏÒÛÂˆÓ Î·È ÙËÓ ÎÏÈÓÈ΋ Ù·ÍÈÓfiÌËÛË Ù˘ ÓfiÛÔ˘. ∫·ı›ÛÙ·Ù·È fiÏÔ Î·È ÂÚÈÛÛfiÙÂÚÔ ÂÌÊ·Ó¤˜ ·fi ÓÂÔÁÓÈο ÚÔÁÚ¿ÌÌ·Ù· ‰È·ÏÔÁ‹˜ Ô˘ ‚·Û›˙ÔÓÙ·È Û ÔÚÌÔÓÈÎÔ‡˜ ÚÔÛ‰ÈÔÚÈÛÌÔ‡˜ Î·È ·fi ÙË ÌÂϤÙË ÔÌ¿‰ˆÓ ÌÂ Û˘ÁÎÂÎÚÈ̤ÓÔ Ê·ÈÓfiÙ˘Ô (˘ÂÚ·Ó‰ÚÔÁÔÓ·ÈÌÈΤ˜ Á˘Ó·›Î˜, ·È‰È¿ Ì ÚÒÈÌË ·‰ÚÂÓ·Ú¯‹) fiÙÈ Ë ·Ó›¯Ó¢ÛË ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ì ÔÚÌÔÓÈΤ˜ ÌÂıfi‰Ô˘˜ ‰ÂÓ Â›Ó·È ·ÎÚÈ‚‹˜ (6). ∏ ·Ó›¯Ó¢ÛË ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ì ÔÚÌÔÓÈÎfi ÚÔÛ‰ÈÔÚÈÛÌfi, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤Ó˘ Î·È Ù˘ ̤ÙÚËÛ˘ Ù˘ 17-√∏ ÚÔÁÂÛÙÂÚfiÓ˘ ÌÂÙ¿ ·fi ‰È¤ÁÂÚÛË Ì ACTH (Synacthen test), ‰ÂÓ Â›Ó·È ¿ÓÙÔÙ ÂÊÈÎÙ‹ Î·È Û˘¯Ó¿ Ù· ‰Â‰Ô̤ӷ ÂÙÂÚÔ˙˘ÁˆÙÒÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÈÎ¿Ï˘„Ë Ì ·˘Ù¿ ˘ÁÈÒÓ ·ÙfiÌˆÓ (7). ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ, ˘ÔÏÔÁÈ˙fiÌÂÓË Ì ÙËÓ Â͛ۈÛË Hardy-Weinberg ·fi ‰Â‰Ô̤ӷ ÓÂÔÁÓÈÎÒÓ ÚÔÁÚ·ÌÌ¿ÙˆÓ ‰È·ÏÔÁ‹˜, Ô˘ ‚·Û›˙ÔÓÙ·Ó ÛÙË Ì¤ÙÚËÛË Ù˘ 17-√∏ ÚÔÁÂÛÙÂÚfiÓ˘, ·Ó¤Ú¯ÂÙ·È Û 1:60 ÁÈ· ÙËÓ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ (8) Î·È 1:17 ÁÈ· ÙË ÌË ÎÏ·ÛÈ΋ ÌÔÚÊ‹ (9). ¶ÂÚÈÔÚÈṲ̂Ó˜, fï˜, ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ Ô˘ ‚·Û›˙ÔÓÙ·È Û ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜, ‰Â›¯ÓÔ˘Ó fiÙÈ Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË. √ ÚÔÛ‰ÈÔÚÈÛÌfi˜ Ù˘ Ú·ÁÌ·ÙÈ΋˜ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Î·È Ù˘ Û¯ÂÙÈ΋˜ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Û ‰È¿ÊÔÚ˜ ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜ Û˘ÓÈÛÙ¿ Ì›· ÛËÌ·ÓÙÈ΋ ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, ÚÔ¸fiıÂÛË ··Ú·›ÙËÙË ÁÈ·

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ÙË ¯ÔÚ‹ÁËÛË ÁÂÓÂÙÈÎÒÓ Û˘Ì‚Ô˘ÏÒÓ. ∏ Û˘¯ÓfiÙËÙ· ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 Î·È ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹, ÂÓÒ ÂÏ¿¯ÈÛÙ· ‰Â‰Ô̤ӷ ˘¿Ú¯Ô˘Ó - ‚·ÛÈṲ̂ӷ Û ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜ - ‰ÈÂıÓÒ˜. ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‹Ù·Ó Ë ·Ó·˙‹ÙËÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ (carrier frequency) Ù˘ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21˘‰ÚÔÍ˘Ï¿Û˘ Î·È Ù˘ Û¯ÂÙÈ΋˜ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÔÚÈ·ÎÒÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ ÎÏ·ÛÈ΋˜ Î·È ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ ÛÂ Ù˘¯·›Ô ‰Â›ÁÌ· ÂÏÏËÓÈÎÔ‡ ÏËı˘ÛÌÔ‡. ªÂ ‚¿ÛË ·˘Ù¿ Ù· ‰Â‰Ô̤ӷ, ı· ˘ÔÏÔÁÈÛÙ› Ë Û˘¯ÓfiÙËÙ· ÙÔ˘ ·ıÔÏÔÁÈÎÔ‡ CYP21 ÁÔÓȉ›Ô˘ (gene frequency), Ë ·fiÏ˘ÙË Û˘¯ÓfiÙËÙ· ÙˆÓ ‰È·ÊfiÚˆÓ ÌÔÚÈ·ÎÒÓ ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ CYP21 ÁÔÓȉ›Ô˘ (allele frequency) Î·È Ë Û˘¯ÓfiÙËÙ· Ù˘ ÓfiÛÔ˘ (disease frequency) ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ∞ӷχıËÎ·Ó 762 ·ÏÏËÏfiÌÔÚÊ· ·fi 381 Ù˘¯·›· ‰Â›ÁÌ·Ù· ·›Ì·ÙÔ˜ ÔÌÊ·Ï›Ô˘ ÏÒÚÔ˘ ÓÂÔÁÓÒÓ Ô˘ ÁÂÓÓ‹ıËÎ·Ó Û ‰È¿ÊÔÚ· Ì·ÈÂ˘Ù‹ÚÈ· fiÏ˘ Ù˘ ∂ÏÏ¿‰Ô˜, ηٿ ÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 2002-2004, ÌÂÙ¿ ·fi ¤ÁÎÚÈÛË ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘˜ (informed consent). ∆· ÓÂÔÁÓ¿ Ô˘ ÌÂÏÂÙ‹ıËÎ·Ó ÚÔ¤Ú¯ÔÓÙ·Ó - ·Ó·ÏÔÁÈο - ·fi ‰È¿ÊÔÚ· ÁˆÁÚ·ÊÈο ‰È·ÌÂÚ›ÛÌ·Ù· Ù˘ ¯ÒÚ·˜ Î·È Ô ·ÚÈıÌfi˜ ÙÔ˘˜ ηıÔÚ›ÛÙËΠ·fi ÙÔÓ ·ÚÈıÌfi ÙˆÓ ÁÂÓÓ‹ÛÂˆÓ ÛÙ· ‰È·ÌÂÚ›ÛÌ·Ù· ·˘Ù¿, Û‡Ìʈӷ Ì ÛÙÔȯ›· Ù˘ ∂ıÓÈ΋˜ ™Ù·ÙÈÛÙÈ΋˜ ÀËÚÂÛ›·˜. ∆· ÓÂÔÁÓ¿ ÚÔ¤Ú¯ÔÓÙ·Ó ·fi ÁÔÓ›˜ ÂÏÏËÓÈ΋˜ ηٷÁˆÁ‹˜. ∏ ·Ú¯È΋ ·ÈÌÔÏË„›· ÁÈÓfiÙ·Ó ·fi ÙÔÓ ÔÌÊ¿ÏÈÔ ÏÒÚÔ ˆ˜ ÂÍ‹˜: ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÙÔÎÂÙÔ‡ Ô ÔÌÊ¿ÏÈÔ˜ ÏÒÚÔ˜ ·ÔÌÔÓÒıËΠ̠ÂÊ·ÚÌÔÁ‹ ‰‡Ô Ï·‚›‰ˆÓ Îfi¯ÂÚ Î·È ÛÙË Û˘Ó¤¯ÂÈ· ¤ÁÈÓ ·ÈÌÔÏË„›· 5 ml ·›Ì·ÙÔ˜, Ô˘ Û˘ÁÎÂÓÙÚÒıËÎ·Ó Û ۈÏËÓ¿ÚÈÔ Ô˘ ÂÚÈ›¯Â ∂D∆∞. ∫·Ù·ÁÚ¿ÊËÎ·Ó ÙÔ Ê‡ÏÔ ÙˆÓ ÓÂÔÁÓÒÓ Î·È Ë Î·Ù·ÁˆÁ‹ ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘˜. ŒÁÈÓ ÚÔÊÔÚÈ΋ Î·È ¤ÁÁÚ·ÊË ÂÓË̤ڈÛË ÙˆÓ ÁÔÓ¤ˆÓ ÙˆÓ ÓÂÔÁÓÒÓ Ô˘ ‚Ú¤ıËÎ·Ó ÂÙÂÚÔ˙˘ÁÒÙ˜. √È ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ ·ÓȯÓ‡ıËÎ·Ó ÛÙÔ DNA ·›Ì·ÙÔ˜ ÔÌÊ·Ï›Ô˘ ÏÒÚÔ˘ ÂȂ‚·ÈÒıËÎ·Ó Ì ÌÔÚȷ΋ ·Ó¿Ï˘ÛË DNA ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ Ô˘ Ï‹ÊıËΠ·fi Ù· ·ÓÙ›ÛÙÔȯ· ÓÂÔÁÓ¿ Î·È ÙÔ˘˜ ÁÔÓ›˜ ÙÔ˘˜.

DNA ·ÔÌÔÓÒıËΠ·fi Ù· ÏÂ˘Î¿ ·ÈÌÔÛÊ·›ÚÈ· ÙÔ˘ ·›Ì·ÙÔ˜ ÙÔ˘ ÔÌÊ·Ï›Ô˘ ÏÒÚÔ˘ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙËÓ Ù¯ÓÈ΋ GFX Genomic Blood DNA Purification Kit

by Amersham Biosciences. °È· ÙËÓ ·Ó›¯Ó¢ÛË ÙˆÓ ÛËÌÂÈ·ÎÒÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë Ì¤ıÔ‰Ô˜ Ù˘ ·Ï˘ÛȉˆÙ‹˜ ·ÓÙ›‰Ú·Û˘ ÔÏ˘ÌÂÚ¿Û˘ Ì ÂÎÏÂÎÙÈÎfi ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙÌ‹Ì·ÙÔ˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ·ÏÏËÏfiÌÔÚÊÔ˘ (allele specific PCR-Amplification refractory mutation system) (10). ∞Ú¯Èο ¤ÁÈÓ ÂÈÏÔÁ‹ ÙˆÓ ·ÏÏËÏÔ˘¯ÈÒÓ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 ·fi ÙÔ ÔÏÈÎfi ÁÔÓȉȷÎfi DNA Ì ·ÓÙ›‰Ú·ÛË PCR, ۯ‰ȷṲ̂ÓË ¤ÙÛÈ ÒÛÙ ӷ ·ÔÎÏ›ÂÈ ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ¶·È‰È·ÙÚÈ΋ 2006;69:286-293

290

∞. ¢·ÛÙ·Ì¿ÓË Î·È Û˘Ó.

·ÏÏËÏÔ˘¯ÈÒÓ ÙÔ˘ CYP21P („¢‰ÔÁÔÓȉ›Ô˘). ™Â οı ‰Â›ÁÌ· ·Ó·˙ËÙ‹ıËÎ·Ó ÔÈ ·ÎfiÏÔ˘ı˜ 12 ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21: ·) √Ìfi˙˘ÁÔ˜ ·¿ÏÂÈ„Ë/ÌÂÙ·ÙÚÔ‹ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21, ‚) ÌÂÙ¿ÏÏ·ÍË P30L Î·È W22X ÛÙÔ ÚÒÙÔ ÂÍÒÓÈÔ, Á) ÌÂÙ¿ÏÏ·ÍË π2splice ÛÙÔ ‰Â‡ÙÂÚÔ ÂÛÒÓÈÔ, ‰) ·¿ÏÂÈ„Ë 8 ‚¿ÛÂˆÓ 8bpdE3 ÛÙÔ ÙÚ›ÙÔ ÂÍÒÓÈÔ, Â) ÌÂÙ¿ÏÏ·ÍË π172¡ ÛÙÔ Ù¤Ù·ÚÙÔ ÂÍÒÓÈÔ, ÛÙ) Û‡ÌÏÂÁÌ· 3 ÌÂÙ·ÏÏ¿ÍÂˆÓ Cluster E6 ÛÙÔ ¤ÎÙÔ ÂÍÒÓÈÔ, ˙) ÌÂÙ¿ÏÏ·ÍË V281L Î·È F306+∆ ÛÙÔ ¤‚‰ÔÌÔ ÂÍÒÓÈÔ, Ë) ÌÂÙ¿ÏÏ·ÍË Q318X Î·È R356W ÛÙÔ fiÁ‰ÔÔ ÂÍÒÓÈÔ, ı) ÌÂÙ¿ÏÏ·ÍË P453S ÛÙÔ ‰¤Î·ÙÔ ÂÍÒÓÈÔ. √È ÂÓÓ¤· ·fi ·˘Ù¤˜ ÙȘ ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘ ÌÂÏÂÙ‹ıËηÓ, ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó ÙÔ 94% ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 Û ÏËı˘ÛÌfi ∂ÏÏ‹ÓˆÓ ·Û¯fiÓÙˆÓ, Û‡Ìʈӷ Ì ÚÔËÁÔ‡ÌÂÓË ÌÂϤÙË ÙÔ˘ ÂÚÁ·ÛÙËÚ›Ô˘ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ (5). ∂Ê·ÚÌfiÛÙËÎÂ Ë ‰ÔÎÈÌ·Û›· x2 ˆ˜ ÎÚÈÙ‹ÚÈÔ “ηϋ˜ ÂÊ·ÚÌÔÁ‹˜” (goodness of fit) Î·È ÛÙË Û˘Ó¤¯ÂÈ· Ë Â͛ۈÛË Hardy-Weinberg, ÚÔÎÂÈ̤ÓÔ˘ Ó· ˘ÔÏÔÁÈÛÙ› Ë Û˘¯ÓfiÙËÙ· ÙÔ˘ ÁÔÓȉ›Ô˘ Î·È Ù˘ ÓfiÛÔ˘ (11).

∞ÔÙÂϤÛÌ·Ù· ∆ÚÈ¿ÓÙ· ÂÓÓ¤· ·fi Ù· 762 ·ÏÏËÏfiÌÔÚÊ· ¤ÊÂÚ·Ó ÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 (5,12%), fiÏ· Û ÂÙÂÚfi˙˘ÁË Î·Ù¿ÛÙ·ÛË. ∞fi Ù· 39 ·˘Ù¿ ·ÏÏËÏfiÌÔÚÊ·, 13 (1,7%) ¤ÊÂÚ·Ó ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ™À∂: 10 Q318X (1,3%), 1 I172N (0,13%), 1 I2splice (0,13%), 1 W22X (0,13%) Î·È 26 (3,4%) ¤ÊÂÚ·Ó ÌÂÙ·ÏÏ¿ÍÂȘ Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Ù˘ ÓfiÛÔ˘: 17 V281L (2,23%), 7 P453S (0,92%), 2 P30L (0,26%). √È ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ ·ÓȯÓ‡ıËÎ·Ó Î·È ÔÈ ·ÓÙ›ÛÙÔȯ˜ Û˘¯ÓfiÙËÙ¤˜ ÙÔ˘˜ Ê·›ÓÔÓÙ·È ÛÙÔ ¶›Ó·Î· 1. ™ÙÔÓ ¶›Ó·Î· 2 ·Ó·ÁÚ¿ÊÔÓÙ·È Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ ÛÙȘ ‰È¿ÊÔÚ˜ ÂÚÈÔ¯¤˜ Ù˘ ∂ÏÏ¿‰·˜, ηıÒ˜ Î·È ÙÔ Â›‰Ô˜ ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Ô˘ ·ÓȯÓ‡ıËÎ·Ó ÛÙȘ ÂÚÈÔ¯¤˜ ·˘Ù¤˜. ™˘ÓÂÒ˜ ÔÛÔÛÙfi 10,2% ÙˆÓ ÓÂÔÁÓÒÓ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‹Ù·Ó ÊÔÚ›˜ ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘. ªÂ ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ ‰ÔÎÈÌ·Û›·˜ ¯2, ‰È·ÈÛÙÒıËÎÂ Û˘Ìʈӛ· ÌÂٷ͇ Ù˘ ·Ú·ÙËÚÔ‡ÌÂÓ˘ (10,2%) Î·È Ù˘ ·Ó·ÌÂÓfiÌÂÓ˘ (9,7%) Û˘¯ÓfiÙËÙ·˜ ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ. ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘

ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Ù˘ ÓfiÛÔ˘ ‹Ù·Ó 3,4% Î·È Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ 6,8%. ªÂ ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ Â͛ۈÛ˘ Hardy-Weinberg ˘ÔÏÔÁ›˙ÂÙ·È fiÙÈ Ë Û˘¯ÓfiÙËÙ· Ù˘ ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ ·Ó¤Ú¯ÂÙ·È Û 1:3.436 Î·È Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Û 1:859. ∏ ˘ÔÏÔÁÈÛı›۷ Û˘¯ÓfiÙËÙ· ÙÔ˘ ÁÔÓȉ›Ô˘ (gene frequency) Â›Ó·È 0.051 (¶›Ó·Î·˜ 3).

™˘˙‹ÙËÛË ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·Ó·Ï‡ıËΠ¤Ó· Ù˘¯·›Ô Î·È ·ÓÙÈÚÔÛˆ¢ÙÈÎfi ‰Â›ÁÌ· ÓÂÔÁÓÒÓ ·fi ‰È¿ÊÔÚ˜ ÂÚÈÔ¯¤˜ Ù˘ ∂ÏÏ¿‰·˜. ∞Ó·˙ËÙ‹ıËÎ·Ó 12 ÌÔÚȷΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 Û 381 ÓÂÔÁÓ¿, ÚÔÎÂÈ̤ÓÔ˘ Ó· ηıÔÚÈÛÙ› Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘ ™À∂ Ô˘ ÔÊ›ÏÂÙ·È Û ·ÓÂ¿ÚÎÂÈ· Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi. ∏ Û‡ÁÎÚÈÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Ù˘ ·ÚÔ‡Û·˜ ¤Ú¢ӷ˜ Ì ÂΛӷ ·fi ÙËÓ ∫›Ó· (12) Î·È ÙË ¡¤· ∑ËÏ·Ó‰›· (9), Ô˘ ¤¯Ô˘Ó Â›Û˘ ÚÔ·„ÂÈ ·fi ÙËÓ ÂÊ·ÚÌÔÁ‹ ÌÔÚÈ·ÎÒÓ Ù¯ÓÈÎÒÓ, Ô‰ËÁ› ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Ë Û˘¯ÓfiÙËÙ· Ù˘ ÓfiÛÔ˘ Î·È ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Â›Ó·È Ôχ ÌÂÁ·Ï‡ÙÂÚË ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi ¤Ó·ÓÙÈ ÙˆÓ ‰‡Ô ·˘ÙÒÓ ÏËı˘ÛÌÒÓ. ∏ ‰È·ÊÔÚ¿ ·˘Ù‹ ÌÔÚ› Ó· ÔÊ›ÏÂÙ·È Û ̛· ÛÂÈÚ¿ ·Ú·ÁfiÓÙˆÓ, fiˆ˜ de novo ÌÂÙ·ÏÏ¿ÍÂȘ ‹ ÙÔ Ê·ÈÓfiÌÂÓÔ ÙÔ˘ È‰Ú˘Ù‹ (founder effect) Û ÔÚÈṲ̂Ó˜ ÁˆÁÚ·ÊÈΤ˜ ÂÚÈÔ¯¤˜ (1). ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi Â›Ó·È ·Ó¿ÏÔÁË Ì ·˘Ù‹ Ù˘ ∞˘ÛÙÚ›·˜ (13) Î·È Ù˘ ÚÒËÓ °ÈÔ˘ÁÎÔÛÏ·‚›·˜ (13), Ô˘ ·Ó·Ê¤ÚÂÙ·È Û ÚfiÛÊ·ÙË ÌÂϤÙË. ∏ Û‡ÁÎÚÈÛË fï˜ ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ÌÂϤÙ˘ ÙÔ˘ ÂÏÏËÓÈÎÔ‡ ÏËı˘ÛÌÔ‡ Ì ٷ ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ ·˘Ù‹˜ ÚÔÛÎÚÔ‡ÂÈ Û ‰È·ÊÔÚ¤˜, ÙfiÛÔ ÛÙËÓ ÂÈÏÔÁ‹ ÙÔ˘ ˘ÏÈÎÔ‡ fiÛÔ Î·È ÛÙÔ Ì¤ÁÂıÔ˜ ÙÔ˘ ‰Â›ÁÌ·ÙÔ˜. ™ÙË ÙÂÏÂ˘Ù·›· ·˘Ù‹ ÌÂϤÙË, Ë ·Ó·˙‹ÙËÛË ÊÔÚ¤ˆÓ ¤ÁÈÓ Û 100 ÂÓ‹ÏÈη ¿ÙÔÌ·, Ô˘ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·Ó Û οÔÈÔ ÓÔÛÔÎÔÌ›Ô, ÂÓÒ ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Ô ·ÚÈıÌfi˜ ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚÔ˜ Î·È Ë ‰ÂÈÁÌ·ÙÔÏË„›· Ù˘¯·›· Î·È ·ÊÔÚ¿ Û ÓÂÔÁÓÈÎfi ÏËı˘ÛÌfi.

¶›Ó·Î·˜ 1. ªÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 Ô˘ ·ÓȯÓ‡ıËÎ·Ó ªÂÙ·ÏÏ¿ÍÂȘ Ô˘ ·ÓȯÓ‡ıËÎ·Ó V281L P453S P30L Q318X I172N I2splice W22X ¶·È‰È·ÙÚÈ΋ 2006;69:286-293

∞ÏÏËÏfiÌÔÚÊ· (n)

%

∫ÏÈÓÈ΋ ÌÔÚÊ‹

17 7 2 10 1 1 1

2,23 0,92 0,26 1,3 0,13 0,13 0,13

NC NC NC C C C C

291

™˘¯ÓfiÙËÙ· ÙˆÓ ÊÔÚ¤ˆÓ Û˘ÁÁÂÓÔ‡˜ ˘ÂÚÏ·Û›·˜ ÂÈÓÂÊÚȉ›ˆÓ

¶›Ó·Î·˜ 2. ™˘¯ÓfiÙËÙ· ÂÙÂÚÔ˙˘ÁˆÙÒÓ ÙÔ˘ ÁÔÓȉ›Ô˘ CYP21 ÛÙȘ ‰È¿ÊÔÚ˜ ÂÚÈÔ¯¤˜ Ù˘ ∂ÏÏ¿‰·˜ ¶ÂÚÈÔ¯‹

∞ÚÈıÌfi˜ ‰ÂÈÁÌ¿ÙˆÓ

∞ÚÈıÌfi˜ ÂÙÂÚÔ˙˘ÁˆÙÒÓ

™˘¯ÓfiÙËÙ· ÂÙÂÚÔ˙˘ÁˆÙÒÓ

∂›‰Ô˜ ÌÂÙ·ÏϿ͈Ó

20 33 11 13 35 32 155 26 50 7

4 6 2 2 4 3 13 2 3 -

20% 18,2% 18,2% 15,4% 11,4% 9,3% 8,4% 7,6% 6% -

V281L Q318X, V281L, P453S, I172N V281L V281L V281L, P453S, I2splice Q318X, P453S Q318X, P453S, V281L, P30L, W22X V281L V281L, P30L -

£Ú¿ÎË ª·Î‰ÔÓ›· ¡. ∞ÈÁ·›Ô˘ ◊ÂÈÚÔ˜ £ÂÛÛ·Ï›· ™ÙÂÚ¿ ∂ÏÏ¿‰· ∞ı‹Ó· ∫Ú‹ÙË ¶ÂÏÔfiÓÓËÛÔ˜ ¡. πÔÓ›Ô˘

∏ Û˘¯ÓfiÙËÙ· Ù˘ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21˘‰ÚÔÍ˘Ï¿Û˘ ·ÁÎÔÛÌ›ˆ˜ (¶›Ó·Î·˜ 4), fiˆ˜ ÚÔ·ÙÂÈ ·fi Ù· ÓÂÔÁÓÈο ÚÔÁÚ¿ÌÌ·Ù· ‰È·ÏÔÁ‹˜ (screening) Ô˘ ‚·Û›˙ÔÓÙ·È ÛÙË Ì¤ÙÚËÛË Ù˘ 17√∏ ÚÔÁÂÛÙÂÚfiÓ˘, ÁÈ· ÙËÓ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ Î˘Ì·›ÓÂÙ·È ·fi 1:5.000 ¤ˆ˜ 1:23.000 ÛÙȘ ‰È¿ÊÔÚ˜ ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜ (14). ™ÙËÓ ∂˘ÚÒË, Ë Û˘¯ÓfiÙËÙ· Ù˘ ™À∂ ·fi ·ÓÂ¿ÚÎÂÈ· Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘ Û ÓÂÔÁÓÈÎfi ÏËı˘ÛÌfi Î˘Ì·›ÓÂÙ·È ·fi 1:11.000 ¤ˆ˜ 1:15.000 (14). ∞fi Ù· ‰Â‰Ô̤ӷ ·˘Ù¿ Î·È ÂÊ·ÚÌfi˙ÔÓÙ·˜ ÙÔÓ ÓfiÌÔ Hardy-Weinberg, ÚÔ·ÙÂÈ fiÙÈ Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘ ™À∂ Â›Ó·È 1,7% ·ÁÎÔÛÌ›ˆ˜ (8), ·ÚÈıÌfi˜ Ô˘ ˘ÔÏ›ÂÙ·È Î·Ù¿ Ôχ ÙÔ˘ Ú·ÁÌ·ÙÈÎÔ‡. ∏ ·ÚÔ‡Û· ÌÂϤÙË Î·Ù·‰ÂÈÎÓ‡ÂÈ fiÙÈ Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ ÁÈ· ÙËÓ ÎÏ·ÛÈ΋ (3,4%) Î·È ÌË ÎÏ·ÛÈ΋ ÌÔÚÊ‹ (6,8%) Ù˘ ™À∂ Â›Ó·È Ôχ ÌÂÁ·Ï‡ÙÂÚË ·fi ÙË Û˘¯ÓfiÙËÙ· Ô˘ ÚÔ·ÙÂÈ ·fi Ù· ‰Â‰Ô̤ӷ ÙˆÓ ÚÔÁÚ·ÌÌ¿ÙˆÓ screening. ∞Ó¿ÏÔÁÔ Â›Ó·È ÙÔ Û˘Ì¤Ú·ÛÌ· Ô˘ ¤¯ÂÈ ÂÍ·¯ı› ·fi ÙË ÌÂϤÙË ÛÙË ¡¤· ∑ËÏ·Ó‰›· (9) Î·È ÛÙËÓ ∞˘ÛÙÚ›· (13). ∏ ‰È·ÊÔÚ¿ ·˘Ù‹ ÌÔÚ› Ó· Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÂÚ›Ô˘ ÙÔ 14% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ù˘ ÎÏ·ÛÈ-

΋˜ ÌÔÚÊ‹˜ Î·È ÙÔ 87% ÙˆÓ ÓÂÔÁÓÒÓ Ì ÌË ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ™À∂ ‰ÂÓ ·ÓȯÓ‡ÔÓÙ·È ÛÙÔÓ ÔÚÌÔÓÈÎfi ¤ÏÂÁ¯Ô Ô˘ Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ÙȘ ÚÒÙ˜ Ë̤Ú˜ ˙ˆ‹˜ (15). ∂Ô̤ӈ˜, ·Ú’ fiÏÔ Ô˘ Ù· ÚÔÁÚ¿ÌÌ·Ù· screening ÛÙ· ÓÂÔÁÓ¿ ¤‰ÂÈÍ·Ó ÌÂÁ·Ï‡ÙÂÚË Û˘¯ÓfiÙËÙ· Ù˘ ÓfiÛÔ˘ Û ۇÁÎÚÈÛË Ì ÙȘ ¤Ú¢Ó˜ (case surveys) Ô˘ η٤ÁÚ·Ê·Ó Ù· ÂÚÈÛÙ·ÙÈο ‚·ÛÈ˙fiÌÂÓ˜ Û ÎÏÈÓÈο ‰Â‰Ô̤ӷ (8), ·Ô‰ÂÈÎÓ‡ÔÓÙ·È ·Ó·ÎÚÈ‚‹ Î·È ˘ÔÂÎÙÈÌÔ‡Ó ÛËÌ·ÓÙÈο ÙË Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘ ™À∂. ™˘ÌÂÚ·ÛÌ·ÙÈο, Ô ÌÔÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ·Ô‰ÂÈÎÓ‡ÂÙ·È ·ÎÚÈ‚¤ÛÙÂÚË Ì¤ıÔ‰Ô˜ ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ÙˆÓ ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21˘‰ÚÔÍ˘Ï¿Û˘ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi. ¶·Ú¿ Ù·‡Ù·, Ë ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÌÔÚÈ·ÎÔ‡ ÂϤÁ¯Ô˘ Û ÌÂÁ·Ï‡ÙÂÚ˜ ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜ Â›Ó·È ‰‡ÛÎÔÏË, ‰ÈfiÙÈ Â›Ó·È È‰È·›ÙÂÚ· ‰··ÓËÚ‹ Î·È ¯ÚÔÓÔ‚fiÚ·. ∂ÈϤÔÓ, Ë ·ÚÔ‡Û· ÌÂϤÙË ‰Â›¯ÓÂÈ fiÙÈ Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÙÔ˘ CYP21 ÁÔÓȉ›Ô˘ ÔÈΛÏÏÂÈ ÛËÌ·ÓÙÈο ÛÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ ÏËı˘ÛÌÔ‡˜ Î·È ‰ÂÓ ÌÔÚ› Ó· ˘ÔÏÔÁÈÛÙ› ·fi ‰Â‰Ô̤ӷ ¿ÏÏˆÓ ÏËı˘ÛÌÈ·ÎÒÓ ÔÌ¿‰ˆÓ. ™ÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi, Ë ϤÔÓ Û˘¯Ó‹ ÌÂÙ¿ÏÏ·ÍË Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÎÏ·ÛÈ΋

¶›Ó·Î·˜ 3. ™˘¯ÓfiÙËÙ˜ ÂÙÂÚÔ˙˘ÁˆÙÒÓ, ÓfiÛÔ˘ Î·È ÁÔÓȉ›Ô˘ Û ‰È¿ÊÔÚ˜ ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜ ¶ÏËı˘ÛÌÔ› / ∞ÚÈıÌfi˜ ‰ÂÈÁÌ¿ÙˆÓ/ ∞ÚÈıÌfi˜ ÌÂÙ·ÏÏ¿ÍÂˆÓ ™˘¯ÓfiÙËÙ· ÂÙÂÚÔ˙˘ÁˆÙÒÓ ™˘¯ÓfiÙËÙ· ÓfiÛÔ˘ Ô˘ ÌÂÏÂÙ‹ıËÎ·Ó ™‡ÓÔÏÔ ªÔÚʤ˜ ™‡ÓÔÏÔ ªÔÚʤ˜

™˘¯ÓfiÙËÙ· ÁÔÓȉ›Ô˘ ™‡ÓÔÏÔ

∫›Ó· / 1000 / 4 ¡¤· ∑ËÏ·Ó‰›· / 603 / 9

0,9% 4,8%

0,0045 0,024

∞˘ÛÙÚ›· / 100 / 13

9%

. °ÈÔ˘ÁÎÔÛÏ·‚›· / 100 / 13

10%

∂ÏÏ¿‰· / 381 / 12

10,2%

0,9% C 2,8% C 2,0% NC 5% C 4% NC 6% C 4% NC 3,4% C 6,8% NC

1:49.382 1:1.729 1:493 1:400 1:382

1:49.382 C 1:5.032 C 1:10.100 NC 1:2.500 C 1:1.111 NC 1:2.500 C 1:1.111 NC 1:3.436 C 1:859 NC

0,045 0,05 0,051

¶·È‰È·ÙÚÈ΋ 2006;69:286-293

292

∞. ¢·ÛÙ·Ì¿ÓË Î·È Û˘Ó.

¶›Ó·Î·˜ 4. ∏ Û˘¯ÓfiÙËÙ· Ù˘ ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Ù˘ ·ÓÂ¿ÚÎÂÈ·˜ Ù˘ 21-˘‰ÚÔÍ˘Ï¿Û˘, ηıÔÚÈ˙fiÌÂÓË ·fi ÔÚÌÔÓÈο ÚÔÁÚ¿ÌÌ·Ù· screening ÓÂÔÁÓÒÓ ¶ÂÚÈÔ¯‹ AÏ¿Ûη, Yupik Eskimos °·ÏÏ›·, La Reunion IÙ·Ï›· IÛÚ·‹Ï ™·Ô˘‰È΋ ∞Ú·‚›· π·ˆÓ›· ™Ô˘Ë‰›· ∏¶∞, T¤Í·˜ N¤· ZËÏ·Ó‰›· °·ÏÏ›·, Lille B¤ÏÁÈÔ ∏¶∞, Wisconsin ∂Ï‚ÂÙ›· √ÏÏ·Ó‰›·

™˘¯ÓfiÙËÙ·

∞ÚÈıÌfi˜ ÂÍÂÙ·Ûı¤ÓÙˆÓ

ŒÎ‰ÔÛË

1:282 1:2.141 1:18.000 1:28.462 1:14.240 1:18.000 1:9.800 1:16.008 1:23.344 1:13.000 1:25.000 1:11.000 1:10.749 1:11.764

1.131 14.987 420.960 113.846 56.958 4.500.000 1.500.000 1.900.000 536.915 408.138 206.108 149.684 333.221 176.684

1982 (16) 1987 (8) 1996 (17) 1997 (18) 1997 (18) 1997 (19) 1998 (20) 1998 (15) 1995 (21) 1999 (22) 1997 (23) 1997 (24) 2002 (25) 2001 (26)

ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘ Â›Ó·È Ë Q318X, ·ÎÔÏÔ˘ıÔ‡ÌÂÓË ·fi ÙËÓ P30L, I2splice Î·È W22X. ∏ ÌÂÙ¿ÏÏ·ÍË V281L ·ÔÙÂÏ› ÙË Û˘¯ÓfiÙÂÚË ÌÔÚȷ΋ ‰È·Ù·Ú·¯‹ Ù˘ ÌË ÎÏ·ÛÈ΋˜ ÌÔÚÊ‹˜ Ù˘ ™À∂, ‰Â‰Ô̤ÓÔ Ô˘ ÂȂ‚·ÈÒÓÂÙ·È ÙfiÛÔ ·fi ¿ÏÏË ÌÂϤÙË Û ÏËı˘ÛÌfi ∂ÏÏ‹ÓˆÓ ·Û¯fiÓÙˆÓ (5), fiÛÔ Î·È ·fi ÌÂϤÙ˜ Ô˘ Ú·ÁÌ·ÙÔÔÈ‹ıËÎ·Ó ‰ÈÂıÓÒ˜ (1). ∏ ˘„ËÏfiÙÂÚË Û˘¯ÓfiÙËÙ· ÂÙÂÚÔ˙˘ÁˆÙÒÓ ·Ú·ÙËÚ‹ıËΠÛÙȘ ÂÚÈÔ¯¤˜ £Ú¿Î˘, ª·Î‰ÔÓ›·˜ Î·È ¡‹ÛˆÓ ∞ÈÁ·›Ô˘, Ë ¯·ÌËÏfiÙÂÚË ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ¶ÂÏÔÔÓÓ‹ÛÔ˘, ÂÓÒ ‰ÂÓ ·ÓȯÓ‡ıËÎ·Ó ÂÙÂÚÔ˙˘ÁÒÙ˜ ÛÙ· πfiÓÈ· ¡ËÛÈ¿. ∆· ‰Â‰Ô̤ӷ Ù˘ ·ÚÔ‡Û·˜ ¤Ú¢ӷ˜ ÚÔÛʤÚÔÓÙ·È ÁÈ· ÙË ‰ËÌÈÔ˘ÚÁ›· ‚¿Û˘ ‰Â‰ÔÌ¤ÓˆÓ ÁÈ· ÙËÓ ÂÊ·ÚÌÔÁ‹ ÚÔÁÚ¿ÌÌ·ÙÔ˜ screening ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi, ÚÔÎÂÈ̤ÓÔ˘ Ó· ÌÂȈı› Ë ÓÔÛËÚfiÙËÙ· Î·È Ë ıÓËÛÈÌfiÙËÙ· Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÎÏ·ÛÈ΋ ÌÔÚÊ‹ Ù˘ ÓfiÛÔ˘. ∂ÈϤÔÓ, ı· ‰È¢ÎÔχÓÔ˘Ó ÙÔÓ ·Ú¯ÈÎfi ‰È·ÁÓˆÛÙÈÎfi ÚÔÛ·Ó·ÙÔÏÈÛÌfi ÛÙË ÌÔÚȷ΋ ‰ÈÂÚ‡ÓËÛË ÂÓfi˜ ¿Û¯ÔÓÙÔ˜ ‹ Ì›·˜ ÔÈÎÔÁ¤ÓÂÈ·˜, Ì ÂÎΛÓËÛË ·fi ÙË Û˘¯ÓfiÙÂÚË ÁÔÓȉȷ΋ ‚Ï¿‚Ë. ∂ÈϤÔÓ, Ë ÁÓÒÛË ÙˆÓ Û˘¯ÓfiÙÂÚˆÓ ÌÔÚÈ·ÎÒÓ ‰È·Ù·Ú·¯ÒÓ ÛÙÔÓ ÂÏÏËÓÈÎfi ÏËı˘ÛÌfi ı· Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ Ù·¯‡ÙÂÚË ·Ó›¯Ó¢ÛË Ù˘ ÌÔÚȷ΋˜ ‰È·Ù·Ú·¯‹˜ ηٿ ÙÔÓ ÚÔÁÂÓÓËÙÈÎfi ¤ÏÂÁ¯Ô ÂÌ‚Ú‡ˆÓ ˘fiÙˆÓ ÁÈ· ™À∂ ηÈ, ηٿ Û˘Ó¤ÂÈ·, ÛÙËÓ ¤ÁηÈÚË ıÂÚ·¢ÙÈ΋ ·Ú¤Ì‚·ÛË Î·È ÚfiÏË„Ë Ù˘ ·ÚÚÂÓÔÔ›ËÛ˘ ÙˆÓ ¤Íˆ ÁÂÓÓËÙÈÎÒÓ ÔÚÁ¿ÓˆÓ ÙÔ˘ ÚÔۂ‚ÏË̤ÓÔ˘ ıËÏ˘ÎÔ‡ ÂÌ‚Ú‡Ô˘. ∆¤ÏÔ˜, ȉȷ›ÙÂÚË ÛËÌ·Û›· ¤¯ÂÈ Ë ¯·ÚÙÔÁÚ¿ÊËÛË ÙÔ˘ ›‰Ô˘˜ ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Î·È Ô ÚÔÛ‰ÈÔÚÈÛÌfi˜ Ù˘ Û˘¯ÓfiÙËÙ¿˜ ÙÔ˘˜, ÁÈ· ÙËÓ ·Ó·ÁÓÒÚÈÛË ÙˆÓ ¶·È‰È·ÙÚÈ΋ 2006;69:286-293

ÂÙÂÚÔ˙˘ÁˆÙÒÓ Ù˘ ÓfiÛÔ˘ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, ÚÔ¸fiıÂÛË ··Ú·›ÙËÙË ÁÈ· ÙË ¯ÔÚ‹ÁËÛË ÁÂÓÂÙÈÎÒÓ Û˘Ì‚Ô˘ÏÒÓ.

∂˘¯·ÚÈÛٛ˜ π‰È·›ÙÂÚ· ¢¯·ÚÈÛÙԇ̠ÙÔ˘˜ Û˘Ó·‰¤ÏÊÔ˘˜ È·ÙÚÔ‡˜ Ô˘ Û˘Ó¤‚·Ï·Ó ÛËÌ·ÓÙÈο ÛÙËÓ ˘ÏÔÔ›ËÛË ·˘Ù‹˜ Ù˘ ÌÂϤÙ˘, ÁÈ· ÙË Û˘ÏÏÔÁ‹ ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ ·fi ÙÔÓ ÔÌÊ¿ÏÈÔ ÏÒÚÔ ÙˆÓ ÓÂÔÁÓÒÓ: °. ∞ÓÙˆÓ¿Î˘ (¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ƒ›Ô˘), °. ¢·ÛÙ·Ì¿ÓË (¡ÔÛÔÎÔÌÂ›Ô “∞ÏÂÍ¿Ó‰Ú·”), ¢È·Ì·ÓÙfiÔ˘ÏÔ˜ (ª·È¢ÙÈ΋ ∫ÏÈÓÈ΋ “πÔÎÚ¿ÙÂÈÔ” ∞ÁÚÈÓ›Ô˘), ∂. ¢Ô˘Ú¿ÙÛÔ˜ (ª·ÈÂ˘Ù‹ÚÈÔ “§ËÙÒ”), ∫·ÙÛ¿ÓÔ˘ (ª·È¢ÙÈ΋ ∫ÏÈÓÈ΋ “ªËÙ¤Ú·” §·Ì›·˜), ∏. ∫·ÙÛ›Î˘ (“πÔÎÚ¿ÙÂÈÔ” £ÂÛÛ·ÏÔӛ΢), º. ∫Ô˘‚‡‰Ë (ª·È¢ÙÈ΋ ∫ÏÈÓÈ΋ “ÕÁÈÔ˜ ∂Ï¢ı¤ÚÈÔ˜”), °. §È¿ÏÈÔ˜ (¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô §¿ÚÈÛ·˜), ™. ™ËÊ¿Î˘ (¶∂¶∞°¡∏ ∫Ú‹Ù˘), £. ™Ù¤ÊÔ˜ (¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô πˆ·ÓÓ›ÓˆÓ), π. ∆ÚÈ·ÓÙ·Ê˘ÏÏ›‰Ë˜ (¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∞ÏÂÍ·Ó‰ÚÔ‡ÔÏ˘), π. ÷Ù˙‹˜ (ª·ÈÂ˘Ù‹ÚÈÔ “ª·Ú›Î· ∏ÏÈ¿‰Ë”).

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Cartigny-Maciejewski M, Guilley N, Vanderbecken S, Gonde S, Stuckens C, Ponte C et al. Neonatal screening of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Lille experience 19801996. Arch Pediatr 1999;6:151-158.

Van der Kamp HJ, Wit JM. Neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol 2004;151 (Suppl 3):U71-U75.

Allen DB, Hoffman GL, Fitzpatrick P, Laessig R, Maby S, Slyper A. Improved precision of newborn screening for congenital adrenal hyperplasia using weight-adjusted criteria for 17-hydroxyprogesterone levels. J Pediatr 1997;130:128-133.

Steigert M, Schoenle EJ, Biason-Lauber A, Torresani T. High reliability of neonatal screening for congenital adrenal hyperplasia in Switzerland. J Clin Endocrinol Metab 2002;87:4106-4110.

Van der Kamp HJ, Noordam K, Elvers B, Van Baarle M, Otten BJ, Verkerk PH. Newborn screening for congenital adrenal hyperplasia in the Netherlands.

Pediatrics 2001;108:1320-1324.

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ORIGINAL ARTICLE

ÀÂÚ¿ÚÈıÌ· ¯ÚˆÌÔÛˆÌÈο ıÚ·‡ÛÌ·Ù· ÚÔÂÚ¯fiÌÂÓ· ·fi ÙÔ ¯ÚˆÌfiۈ̷ 15: Û˘Û¯¤ÙÈÛË Ê·ÈÓÔÙ‡Ô˘ - ÁÔÓÔÙ‡Ô˘ ∂ÚÁ·ÛÙ‹ÚÈÔ π·ÙÚÈ΋˜ °ÂÓÂÙÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: AÁÁÂÏÈ΋ ∫ÔÏȷϤÍË ∂ÚÁ·ÛÙ‹ÚÈÔ π·ÙÚÈ΋˜ °ÂÓÂÙÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·” ∆.∫. 115 27, °Ô˘‰›, ∞ı‹Ó· E-mail: akolial@cc.uoa.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 18-01-2006 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 17-04-2006

∞. ∫ÔÏȷϤÍË, ™. ∫›ÙÛÈÔ˘, Œ. ºÚ˘Û›Ú·, Ã. ™ÔÊÔÎÏ¤Ô˘˜, ∂. ∫Ô˘‚›‰Ë, ∫. ™·Ï·‚Ô‡Ú·, ∞. ª·‡ÚÔ˘

¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: ∆· ˘ÂÚ¿ÚÈıÌ· ¯ÚˆÌÔÛˆÌÈο ıÚ·‡ÛÌ·Ù· (SMCs) ·ÔÙÂÏÔ‡Ó Û¿ÓȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Î·È ÚÔηÏÔ‡Ó ÌÂÚÈ΋ ÙÚÈۈ̛· ÂÚÈÔ¯ÒÓ ÙÔ˘ ÁÔÓȉÈÒÌ·ÙÔ˜ Ì ¯·Ú·ÎÙËÚÈÛÙÈΤ˜ Ê·ÈÓÔÙ˘ÈΤ˜ ÂÈÙÒÛÂȘ. ŸÛ· ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙÔ ¯ÚˆÌfiۈ̷ 15 ·ÔÙÂÏÔ‡Ó ÙÔ 50% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Î·È ¤¯Ô˘Ó Èı·ÓÒ˜ ÙË ÌÂÁ·Ï‡ÙÂÚË ÛËÌ·Û›·, ‰ÈfiÙÈ ÛÙÔ ¯ÚˆÌfiۈ̷ ·˘Ùfi ÂÓÙÔ›˙ÂÙ·È Ë ÎÚ›ÛÈÌË ÂÚÈÔ¯‹ ÙˆÓ Û˘Ó‰ÚfiÌˆÓ Prader-Willi/Angelman (PWS/AS), ÛÙËÓ ÔÔ›· ·Ú·ÙËÚÂ›Ù·È ÁÔÓȉȷ΋ ·ÔÙ‡ˆÛË. ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ¶·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· Â˘Ú‹Ì·Ù· ·fi ÙË ‰ÈÂÚ‡ÓËÛË 16 ÂÚÈÙÒÛÂˆÓ Ì SMC(15)s. ∏ ·Ú¯È΋ ÂÓÙfiÈÛË ¤ÁÈÓ Ì ÎÏ·ÛÈ΋ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË Û 14 ·È‰È¿ Î·È Û 2 ‰Â›ÁÌ·Ù· ·ÌÓÈ·ÎÔ‡ ˘ÁÚÔ‡ Î·È Ë ¯ÚˆÌÔÛˆÌÈ΋ ÙÔ˘˜ ÚԤϢÛË Ù·˘ÙÔÔÈ‹ıËΠ̠ÊıÔÚ›˙ÔÓÙ· in situ ˘‚ÚȉÈÛÌfi. ™Â fiϘ ÙȘ ÂÚÈÙÒÛÂȘ ÌÂÏÂÙ‹ıËÎÂ Ô Î·Ú˘fiÙ˘Ô˜ ÙˆÓ ÁÔÓ¤ˆÓ. ∞ÔÙÂϤÛÌ·Ù·: ™Â 15/16 ÂÚÈÙÒÛÂȘ (93,75%) ÙÔ SMC(15) ‚Ú¤ıËΠ۠ÔÛÔÛÙfi 100% ÙˆÓ ÌÂÙ·Ê¿ÛÂˆÓ Î·È ÌfiÓÔ Û ̛· (6,25%) ‹Ù·Ó ̈۷˚Îfi. ™Â 14 ÂÚÈÙÒÛÂȘ (87,5%) ÙÔ SMC(15) ‹Ù·Ó de novo Î·È Û 2 (12,5%) ÎÏËÚÔÓÔÌÈÎfi. ªÈÎÚ¿ SMC(15)s ·ÓȯÓ‡ÙËÎ·Ó Û 9/16 ÂÚÈÙÒÛÂȘ. ∂Ù¿ ÂÚÈÛÙ·ÙÈο Ì ÌÂÁ¿ÏÔ˘ ÌÂÁ¤ıÔ˘˜ SMC(15) ÌÂÏÂÙ‹ıËÎ·Ó Ì ÙÔÓ ·ÓȯÓÂ˘Ù‹ SNRPN/15qtel ÁÈ· ÙËÓ ÎÚ›ÛÈÌË ÂÚÈÔ¯‹ ÙˆÓ Û˘Ó‰ÚfiÌˆÓ PWS/AS. ™Â ‰‡Ô ·fi ·˘Ù¿ Ô˘ ÂÚÈ›¯·Ó ÙËÓ ÎÚ›ÛÈÌË ÂÚÈÔ¯‹, ·ÎÔÏÔ‡ıËÛ ÌÔÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜, Ô ÔÔ›Ô˜ ÂȂ‚·›ˆÛ ÙËÓ ·ÚÔ˘Û›· 3 ·ÏÏËÏfiÌÔÚÊˆÓ Ù˘ ÎÚ›ÛÈÌ˘ ÂÚÈÔ¯‹˜ PWS/AS Î·È ¤‰ÂÈÍ fiÙÈ ÙÔ SMC(15) ‹Ù·Ó ÌËÙÚÈ΋˜ ÚÔ¤Ï¢Û˘. ªÂϤÙË, fï˜, ÙÔ˘ ÚÔÙ‡Ô˘ ÌÂı˘Ï›ˆÛ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ ·¤ÎÏÂÈÛ ÙË ‰È¿ÁÓˆÛË Û˘Ó‰ÚfiÌˆÓ PWS/AS. ™˘ÌÂÚ¿ÛÌ·Ù·: ∆· Â˘Ú‹Ì·Ù· Ù˘ ÌÂϤÙ˘ ÂÈÛËÌ·›ÓÔ˘Ó ÙË ÛËÌ·Û›· ÙÔ˘ ÔÏÔÎÏËڈ̤ÓÔ˘ ÁÂÓÂÙÈÎÔ‡ ÂϤÁ¯Ô˘ ÙˆÓ SMC(15)s ÁÈ· ÙË Û˘Û¯¤ÙÈÛË ÁÔÓÔÙ‡Ô˘ - Ê·ÈÓÔÙ‡Ô˘ Î·È ÙË ÁÂÓÂÙÈ΋ ηıÔ‰‹ÁËÛË ÙˆÓ ÔÈÎÔÁÂÓÂÈÒÓ.

§¤ÍÂȘ ÎÏÂȉȿ: ÀÂÚ¿ÚÈıÌÔ ¯ÚˆÌÔÛˆÌÈÎfi ıÚ·‡ÛÌ·, ¯ÚˆÌfiۈ̷ 15.

Supernumerary marker chromosomes derived from chromosome 15: phenotype - genotype correlation Laboratory of Medical Genetics, University of Athens, “Aghia Sofia” Children’s Hospital Correspondence: Aggeliki Kolialexi Laboratory of Medical Genetics, University of Athens “Aghia Sofia” Children’s Hospital 115 27, Goudi, Athens E-mail: akolial@cc.uoa.gr Date of submission: 18-01-2006 Date of approval: 17-04-2006

¶·È‰È·ÙÚÈ΋ 2006;69:294-300

A. Kolialexi, S. Kitsiou, H. Fryssira, C. Sofocleous, E. Kouvidi, K. Salavoura, A. Mavrou

Abstract Background: Supernumerary marker chromosomes (SMCs) are rare chromosomal abnormalities

which cause partial trisomy of genomic regions with characteristic phenotypic effects. Those derived from chromosome 15 account for 50% of cases and are of great importance because this chromosome includes the critical region for the Prader-Willi/Angelman syndromes (PWS/AS).

Methods: The results of investigation of 16 cases of SMC(15) are presented. The initial identification was made by conventional cytogenetics analysis in 14 children and 2 amniotic fluid samples, and their chromosomal origin was determined by fluorescence in situ hybridisation (FISH). Parental karyotypes were studied in all cases.

Results: In 15/16 (93.75%) cases the SMC(15) was found in 100% of metaphases and in one (6.25%) it was mosaic. In 14/16 (87.5%) cases the SMC(15) was de novo while in the remaining two (12.5%) it was familial. Small SMC(15)s were found in 9/16 cases. Seven of 16 cases with large SMC(15)s were studied for the PWS/AS critical region with the SNRPN/15qtel probe. In two which contained the critical region,

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ªÂÚÈ΋ ÙÚÈۈ̛· 15: Ê·ÈÓfiÙ˘Ô˜-ÁÔÓfiÙ˘Ô˜

subsequent molecular study confirmed the presence of 3 alleles of the PWS/AS critical region and showed that SMC(15) was maternally-derived. The study of the methylation pattern in these patients, however, excluded the diagnosis of PWS/AS. Conclusions: This study illustrates the significance of genetic investigation of SMC(15)s for genotype phenotype correlation and genetic counseling.

Key words: Supernumerary marker chromosome, chromosome 15.

™˘ÓÙÔÌÔÁڷʛ˜ SMCs FISH PWS/AS UPD WCP

ÀÂÚ¿ÚÈıÌ· ¯ÚˆÌÔÛˆÌÈο ıÚ·‡ÛÌ·Ù· ºıÔÚ›˙ˆÓ in situ ˘‚ÚȉÈÛÌfi˜ ™‡Ó‰ÚÔÌ· Prader-Willi/Angelman MÔÓÔÁÔÓÂ˚΋ ‰Èۈ̛· AÓȯÓÂ˘Ù‹˜ ÁÈ· ÔÏfiÎÏËÚÔ ÙÔ ¯ÚˆÌfiۈ̷ Ì ÙË Ì¤ıÔ‰Ô ‚·Ê‹˜ D¡RP ¶ÔÏ˘ÌÔÚÊÈÎo› ‰ÈÓÔ˘ÎÏÂÔÙȉÈÎÔ› ‰Â›ÎÙ˜ MSPCR T¯ÓÈ΋ ·Ï˘ÛȉˆÙ‹˜ ·ÓÙ›‰Ú·Û˘ ÔÏ˘ÌÂÚ¿Û˘ ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ÙÔ˘ ÚÔÙ‡Ô˘ ÌÂı˘Ï›ˆÛ˘

EÈÛ·ÁˆÁ‹ ∆· ˘ÂÚ¿ÚÈıÌ· ¯ÚˆÌÔÛˆÌÈο ıÚ·‡ÛÌ·Ù· (supernumerary marker chromosomes - SMCs) ·ÔÙÂÏÔ‡Ó ÂÙÂÚÔÁÂÓ‹ ÔÌ¿‰· ·ÚÈıÌËÙÈÎÒÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ Ô˘ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi ÌÂÚÈ΋ ÙÚÈۈ̛· ÔÚÈÛÌ¤ÓˆÓ ÂÚÈÔ¯ÒÓ ÙÔ˘ ÁÔÓȉÈÒÌ·ÙÔ˜ (1). ∏ Û˘¯ÓfiÙËÙ¿ ÙÔ˘˜ Î˘Ì·›ÓÂÙ·È ·fi 0,14 ¤ˆ˜ 0,72 ·Ó¿ 1000 ÁÂÓÓ‹ÛÂȘ, ÂÓÒ ÛÙÔÓ ÚÔÁÂÓÓËÙÈÎfi ¤ÏÂÁ¯Ô Â›Ó·È 0,06-0,1%, ÔÛÔÛÙfi Ô˘ ·ÓÙÈÛÙÔȯ› ÛÙÔ 5% ÙˆÓ ÂÌ‚Ú‡ˆÓ Ô˘ ÂϤÁ¯ÔÓÙ·È (1,2). ∏ ÎÏ·ÛÈ΋ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋ Ô˘ ÛÙËÚ›˙ÂÙ·È ÛÙËÓ ·Ó¿Ï˘ÛË Ù·ÈÓÈÒÓ ÛÙ· ¯ÚˆÌÔÛÒÌ·Ù· ‰ÂÓ Â·ÚΛ ÁÈ· ÙËÓ Ù·˘ÙÔÔ›ËÛË Ù‹˜ ¯ÚˆÌÔÛˆÌÈ΋˜ ÚÔ¤Ï¢Û˘ ÙˆÓ SMCs, ÂÂȉ‹ Û˘Ó‹ıˆ˜ Â›Ó·È Ôχ ÌÈÎÚÔ‡ ÌÂÁ¤ıÔ˘˜ Î·È ‰ÂÓ ¤¯Ô˘Ó ‰È·ÁÓˆÛÙÈΤ˜ Ù·Èӛ˜. ∏ ·Ó¿Ù˘ÍË Ù˘ Ù¯ÓÈ΋˜ ÙÔ˘ ÊıÔÚ›˙ÔÓÙÔ˜ in situ ˘‚ÚȉÈÛÌÔ‡ (FISH) ¤‰ˆÛ Ӥ˜ ‰˘Ó·ÙfiÙËÙ˜ ÛÙËÓ ÂÚÁ·ÛÙËÚȷ΋ ‰ÈÂÚ‡ÓËÛË ÙˆÓ SMCs Î·È ÛÙË Û˘Û¯¤ÙÈÛ‹ ÙÔ˘˜ Ì ¤Ó·Ó Û˘ÁÎÂÎÚÈ̤ÓÔ ÎÏÈÓÈÎfi Ê·ÈÓfiÙ˘Ô (2,3). √È Ê·ÈÓÔÙ˘ÈΤ˜ ÂÈÙÒÛÂȘ ·fi ÙËÓ ·ÚÔ˘Û›· ÙˆÓ SMCs Â›Ó·È ÔÈΛϘ Î·È ÂÍ·ÚÙÒÓÙ·È Î˘Ú›ˆ˜ ·fi ÙË ¯ÚˆÌÔÛˆÌÈ΋ ÙÔ˘˜ ÚԤϢÛË, ÙÔ Ì¤ÁÂıfi˜ ÙÔ˘˜ Î·È ÙËÓ ·ÚÔ˘Û›· ÙÔ˘˜ ÛÙÔÓ Î·Ú˘fiÙ˘Ô ÂÓfi˜ ·fi ÙÔ˘˜ ‰‡Ô ÁÔÓ›˜ (4). ∂¿Ó Ù· SMCs Â›Ó·È ÌÈÎÚ¿ Î·È ·ÔÙÂÏÔ‡ÓÙ·È ·fi ‰ÔÚ˘ÊÔÚÈÎfi ˘ÏÈÎfi ·ÎÚÔÎÂÓÙÚÈÎÒÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Â›Ó·È ·Û˘Ìو̷ÙÈο. ∆Ô ›‰ÈÔ ÈÛ¯‡ÂÈ Î·È

ÁÈ· ÙÔ ÙÔ 70% ÙˆÓ ÌÈÎÚÒÓ SMCs Ô˘ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÌË ·ÎÚÔÎÂÓÙÚÈο ¯ÚˆÌÔÛÒÌ·Ù·. ªÂÁ·Ï‡ÙÂÚ· SMCs, fï˜, ·Ó¿ÏÔÁ· Ì ÙË ¯ÚˆÌÔÛˆÌÈ΋ ÙÔ˘˜ ÚԤϢÛË, ÌÔÚ› Ó· ÚÔηϤÛÔ˘Ó ÛÔ‚·ÚÔ‡ ‚·ıÌÔ‡ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË Î·È Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ (5,6). ™Â ÂÚÈÙÒÛÂȘ Ô˘ ÙÔ SMC ·ÓȯÓ‡ÂÙ·È ÛÙÔÓ ÚÔÁÂÓÓËÙÈÎfi ¤ÏÂÁ¯Ô Î·È ˘¿Ú¯ÂÈ Î·È Û ¤Ó·Ó ·fi ÙÔ˘˜ ÁÔÓ›˜, Ô Î›Ó‰˘ÓÔ˜ ·ıÔÏÔÁÈÎÔ‡ Ê·ÈÓÔÙ‡Ô˘ Â›Ó·È ÌÈÎÚfi˜ Î·È Î·Ù¿ ¿Û· Èı·ÓfiÙËÙ· ı· ¤¯ÂÈ ÙÔÓ ›‰ÈÔ Ê·ÈÓfiÙ˘Ô Ì ÙÔÓ ÁÔÓ¤·. ∂¿Ó, fï˜, ÙÔ ¯ÚˆÌÔÛˆÌÈÎfi ıÚ·‡ÛÌ· Â›Ó·È de novo, ÙfiÙÂ Ô Î›Ó‰˘ÓÔ˜ Ó· Û˘Óԉ‡ÂÙ·È ·fi ·ıÔÏÔÁÈÎfi Ê·ÈÓfiÙ˘Ô ˘ÔÏÔÁ›˙ÂÙ·È Û 13%, fiˆ˜ ÚÔ·ÙÂÈ ·fi ÌÂϤÙË 377.000 ·ÌÓÈÔ·Ú·ÎÂÓÙ‹ÛÂˆÓ (7). ¶ÔÛÔÛÙfi 50% ÙˆÓ ˘ÂÚ¿ÚÈıÌˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ıÚ·˘ÛÌ¿ÙˆÓ ·ÔÙÂÏÔ‡Ó ÙÌ‹Ì·Ù· ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15 Î·È ÔÈ Ê·ÈÓÔÙ˘ÈΤ˜ ÙÔ˘˜ ÂÈÙÒÛÂȘ ÂÍ·ÚÙÒÓÙ·È Î˘Ú›ˆ˜ ·fi ÙËÓ ‡·ÚÍË ‹ fi¯È Ù˘ ÎÚ›ÛÈÌ˘ ÂÚÈÔ¯‹˜ ÙˆÓ Û˘Ó‰ÚfiÌˆÓ Prader-Willi/Angelman (PWS/AS) (2). ªÈÎÚ¿ SMC(15), de novo ‹ ÔÈÎÔÁÂÓ‹, Ù· ÔÔ›· ‰ÂÓ ÂÚȤ¯Ô˘Ó ¢¯ÚˆÌ·Ù›ÓË Ô‡Ù ÙËÓ ÎÚ›ÛÈÌË ÂÚÈÔ¯‹ PWS/AS, ‰ÂÓ Û¯ÂÙ›˙ÔÓÙ·È ¿ÌÂÛ· Ì ·ıÔÏÔÁÈÎfi Ê·ÈÓfiÙ˘Ô (6). ªÂÁ·Ï‡ÙÂÚ· SMC(15) Ô˘ ÂÚȤ¯Ô˘Ó ÙËÓ ÎÚ›ÛÈÌË ÂÚÈÔ¯‹ PWS/AS, Â›Ó·È Û¯Â‰fiÓ ¿ÓÙ· de novo, ÌËÙÚÈ΋˜ ÚÔ¤Ï¢Û˘ Î·È Û˘Óԉ‡ÔÓÙ·È ·fi ÛÔ‚·ÚÔ‡ ‚·ıÌÔ‡ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË Î·È Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ (6). ¶·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÂÏÏ›ÌÌ·Ù· ÛÙËÓ ÂÚÈÔ¯‹ q11-q13 ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15 ·ÔÙÂÏÔ‡Ó ÙËÓ ÈÔ Û˘¯Ó‹ ·ÈÙ›· ÂΉ‹ÏˆÛ˘ Û˘Ó‰ÚfiÌˆÓ PWS (70%) Î·È AS (60%), ÔÛÔÛÙfi 2530% ÙˆÓ ·ÛıÂÓÒÓ Ì PWS Î·È 3-5% Ì AS ÂÌÊ·Ó›˙Ô˘Ó ÌËÙÚÈ΋ ‹ ·ÙÚÈ΋, ·ÓÙ›ÛÙÔȯ·, ÌÔÓÔÁÔÓÂ˚΋ ‰Èۈ̛· (UPD) Î·È Ôχ ÌÈÎÚfiÙÂÚ· ÔÛÔÛÙ¿ ÙˆÓ Û˘Ó‰ÚfiÌˆÓ PWS/AS (1-5%) ÔÊ›ÏÔÓÙ·È Û ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ Î¤ÓÙÚÔ ÁÔÓȉȷ΋˜ ·ÔÙ‡ˆÛ˘. ™Â fiϘ ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ, Ë Ù¯ÓÈ΋ MSPCR Ô˘ ÌÂÏÂÙ¿ ÙÔ ÚfiÙ˘Ô ÌÂı˘Ï›ˆÛ˘ ÙÔ˘ ÂÍˆÓ›Ô˘ 1 ÙÔ˘ ÁÔÓȉ›Ô˘ SNRPN ÛÙËÓ ÎÚ›ÛÈÌË ÁÈ· ÙÔ PW/AS ÂÚÈÔ¯‹, ¶·È‰È·ÙÚÈ΋ 2006;69:294-300

296

∞. ∫ÔÏȷϤÍË Î·È Û˘Ó.

ÂÍ·ÛÊ·Ï›˙ÂÈ ÙË ‰È¿ÁÓˆÛË Ì ÙËÓ ·ÔÎ¿Ï˘„Ë ÌË Ê˘ÛÈÔÏÔÁÈÎÔ‡ ÚÔÙ‡Ô˘. ∆o ÂÍÒÓÈÔ 1 Î·È Ô ˘ÔÎÈÓËÙ‹˜ ÙÔ˘ ÁÔÓȉ›Ô˘ SNRPN ‚Ú›ÛÎÔÓÙ·È Ì¤Û· Û ̛· ÓËÛ›‰· CpG, Ë ÔÔ›· - ˆ˜ ·ÔÙ¤ÏÂÛÌ· ·ÏÏËÏÂȉڿÛÂˆÓ ÌÂٷ͇ ÙˆÓ Î¤ÓÙÚˆÓ ÁÔÓȉȷ΋˜ ·ÔÙ‡ˆÛ˘ ÙÔ˘ ÌËÙÚÈÎÔ‡ Î·È ·ÙÚÈÎÔ‡ ·ÏÏËÏÔÌfiÚÊÔ˘ - Ê·›ÓÂÙ·È Ó· Â›Ó·È ÌÂı˘ÏȈ̤ÓË ÛÙÔ ÌËÙÚÈÎfi Î·È ÌË ÌÂı˘ÏȈ̤ÓË ÛÙÔ ·ÙÚÈÎfi. ø˜ ÌË ÌÂı˘ÏȈ̤ÓË Ë ÂÚÈÔ¯‹ ·˘Ù‹ ÛÙÔ ·ÙÚÈÎfi ·ÏÏËÏfiÌÔÚÊÔ ‰È·ÙËÚÂ›Ù·È ÂÓÂÚÁ‹ Î·È ÈÛÙ‡ÂÙ·È fiÙÈ Ú˘ıÌ›˙ÂÈ ÙËÓ ¤ÎÊÚ·ÛË fiÏˆÓ Û¯Â‰fiÓ ÙˆÓ ÁÔÓȉ›ˆÓ Ù˘ ÎÚ›ÛÈÌ˘ ÂÚÈÔ¯‹˜. ™Â ÂÚ›ÙˆÛË ·ÚÔ˘Û›·˜ ¯ÚˆÌÔÛˆÌÈÎÔ‡ ıÚ·‡ÛÌ·ÙÔ˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ ÂÚÈÔ¯‹ 15q11-q13, ˘¿Ú¯ÂÈ Èı·ÓfiÙËÙ· ‰È·ÊÔÚÔÔ›ËÛ˘ ÙÔ˘ Ê˘ÛÈÔÏÔÁÈÎÔ‡ ÚÔÙ‡Ô˘ ÌÂı˘Ï›ˆÛ˘, ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÚÔÛÔÌÔ›ˆÛ˘ ÙÔ˘ ·ıÔÁÂÓÂÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ Ô˘ ÂÈÎÚ·Ù› Î·È ÛÙË ÌÔÓÔÁÔÓÂ˚΋ ‰Èۈ̛·. ™ÙË ‚È‚ÏÈÔÁÚ·Ê›· ·Ó·Ê¤ÚÔÓÙ·È ÂÚ›Ô˘ 30 ·ÛıÂÓ›˜ Ì SMC(15) Î·È Ê·ÈÓfiÙ˘Ô PWS, fiÔ˘ Û fiϘ ÙȘ ÂÚÈÙÒÛÂȘ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ÌÔÓÔÁÔÓÂ˚΋˜ ‰Èۈ̛·˜ (6-11). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· Â˘Ú‹Ì·Ù· Ù˘ ÁÂÓÂÙÈ΋˜ ·Ó¿Ï˘Û˘ 16 ÂÚÈÙÒÛÂˆÓ SMCs Ô˘ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙÔ ¯ÚˆÌfiۈ̷ 15 Î·È Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· Û‡Ó‰ÂÛ˘ ÙÔ˘ ÁÔÓÔÙ‡Ô˘ Ì ÙÔÓ Ê·ÈÓfiÙ˘Ô.

ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È 14 ·È‰È¿ ËÏÈΛ·˜ 4 ÌËÓÒÓ ¤ˆ˜ 10 ÂÙÒÓ Î·È 2 ‰Â›ÁÌ·Ù· ·ÌÓÈ·ÎÔ‡ ˘ÁÚÔ‡ ·fi ÙÔ ‰Â‡ÙÂÚÔ ÙÚ›ÌËÓÔ Ù˘ ·ËÛ˘, ÛÙÔÓ Î·Ú˘fiÙ˘Ô ÙˆÓ ÔÔ›ˆÓ ‰È·ÈÛÙÒıËΠ˘ÂÚ¿ÚÈıÌÔ ¯ÚˆÌÔÛˆÌÈÎfi ıÚ·‡ÛÌ·. √È Ì¤ıÔ‰ÔÈ Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÁÈ· ÙË ÌÂϤÙË ÂÚÈÂÏ¿Ì‚·Ó·Ó: ·) ∫˘ÙÙ·ÚÔÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË: ∏ ÌÂϤÙË ÙÔ˘ ηڢÔÙ‡Ô˘ ¤ÁÈÓ Û ÌÂÙ·Ê·ÛÈο ¯ÚˆÌÔÛÒÌ·Ù· ÌÂÙ¿ ·fi ηÏÏȤÚÁÂÈ· ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ‹ ΢ÙÙ¿ÚˆÓ ·ÌÓÈ·ÎÔ‡ ˘ÁÚÔ‡ Î·È Û‹Ì·ÓÛË Ì ٷÈӛ˜ G (12). ™Â fiϘ ÙȘ ÂÚÈÙÒÛÂȘ ÌÂÏÂÙ‹ıËÎÂ Ô Î·Ú˘fiÙ˘Ô˜ ÙˆÓ ÁÔÓ¤ˆÓ. ‚) ºıÔÚ›˙ˆÓ in situ ˘‚ÚȉÈÛÌfi˜ (FISH): ∏ Ù·˘ÙÔÔ›ËÛË Ù˘ ¯ÚˆÌÔÛˆÌÈ΋˜ ÚÔ¤Ï¢Û˘ ÙÔ˘ ˘ÂÚ¿ÚÈıÌÔ˘ ¯ÚˆÌÔÛˆÌÈÎÔ‡ ıÚ·‡ÛÌ·ÙÔ˜ ¤ÁÈÓ Ì ÙËÓ Ù¯ÓÈ΋ FISH Û ÌÂÙ·Ê·ÛÈο ¯ÚˆÌÔÛÒÌ·Ù·. ™ÙË ÌÂϤÙË ¯ÚËÛÈÌÔÔÈ‹ıËηÓ: i) Ô ·ÓȯÓÂ˘Ù‹˜ ÁÈ· ÔÏfiÎÏËÚÔ ÙÔ ¯ÚˆÌfiۈ̷ 15 Ì ÙË Ì¤ıÔ‰Ô ‚·Ê‹˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ (whole chromosome paints - WCP) (Cambio) Î·È ii) Ô ·ÓȯÓÂ˘Ù‹˜ SNRPN/15qtel, Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ ÁÔÓ›‰ÈÔ SNRPN ÛÙËÓ Ù·ÈÓ›· 15q11-q13 Î·È ÙÔÓ ÙÂÏÔÌÂÚȉȷÎfi ‰Â›ÎÙË ÙˆÓ Ì·ÎÚÒÓ ÛÎÂÏÒÓ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15 (15qtel). Á) ªÔÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜: ∏ ·ÔÌfiÓˆÛË ÁÂÓˆÌÈÎÔ‡ ¶·È‰È·ÙÚÈ΋ 2006;69:294-300

DNA ·fi Ù· ·È‰È¿ Î·È ÙÔ˘˜ ÁÔÓ›˜ ÙÔ˘˜ ¤ÁÈÓ Ì ÙÔ ÂÌÔÚÈο ‰È·ı¤ÛÈÌÔ Qiamp Blood Mini Kit (Qiagen). ∏ Ù·˘ÙÔÔ›ËÛË Ù˘ ÁÔÓÂ˚΋˜ ÚÔ¤Ï¢Û˘ ÙÔ˘ SMC Î·È Ë ‰ÈÂÚ‡ÓËÛË Èı·Ó‹˜ UPD ¤ÁÈÓ Ì ·Ó¿Ï˘ÛË 8 D¡RPs, ¤ÍÈ (D15S543, D15S11, D15S10, D15S113, GABRB3, D15S97) ·fi ÙËÓ ÎÚ›ÛÈÌË ÂÚÈÔ¯‹ PWS/AS Î·È ‰‡Ô (CYP19, D15S87) ·fi ÙËÓ ÙÂÏÔÌÂÚȉȷ΋ ÂÚÈÔ¯‹ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15 Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ·Ó·Ï‡ıËÎ·Ó ÛÙÔÓ ·˘ÙfiÌ·ÙÔ ·Ó·Ï˘Ù‹ Open GeneTM System Ù˘Visible Genetics. √ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ÚÔÙ‡Ô˘ ÌÂı˘Ï›ˆÛ˘ Ù˘ ÎÚ›ÛÈÌ˘ ÂÚÈÔ¯‹˜ ÙÔ˘ PWS/AS ¤ÁÈÓ Ì ÌÂϤÙË ÙÔ˘ ÂÍˆÓ›Ô˘ 1 ÛÙÔ ÁÔÓ›‰ÈÔ SNRPN Ì ÙËÓ ÂȉÈ΋ Ù¯ÓÈ΋ ·Ï˘ÛȉˆÙ‹˜ ·ÓÙ›‰Ú·Û˘ ÔÏ˘ÌÂÚ¿Û˘ (MSPCR) ÌÂÙ¿ ·fi ¯ËÌÈ΋ ÙÚÔÔÔ›ËÛË ÙÔ˘ DNA Ì ÙÔ ÂÌÔÚÈο ‰È·ı¤ÛÈÌÔ CpG GenomeTM Modification Kit (Q-BIOgene).

∞ÔÙÂϤÛÌ·Ù· ™Â fiϘ ÙȘ ÂÚÈÙÒÛÂȘ, ÙÔ SMC ÂÓÙÔ›ÛÙËΠ·Ú¯Èο Ì ÎÏ·ÛÈ΋ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË (¶›Ó·Î·˜ 1, ∂ÈÎfiÓ· 1). ™Â 15 ·fi ÙȘ 16 ÂÚÈÙÒÛÂȘ (93,75%) ÙÔ SMC ˘‹Ú¯Â ÛÙÔ 100% ÙˆÓ ÌÂÙ·Ê¿ÛÂˆÓ Ô˘ ÌÂÏÂÙ‹ıËÎ·Ó Î·È ÌfiÓÔ ÛÙÔÓ ·ÛıÂÓ‹ ¡Ô 1 ‹Ù·Ó Û ̈۷˚Îfi, Û ÔÛÔÛÙfi 45%. √ ηڢfiÙ˘Ô˜ ÙˆÓ ÁÔÓ¤ˆÓ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi˜ Û 14/16 ÂÚÈÙÒÛÂȘ (87,5%). ™ÙÔÓ ·Ù¤Ú· ÙÔ˘ ·ÛıÂÓ‹ ¡Ô 1 ·ÓȯÓ‡ÙËΠ۠ÔÛÔÛÙfi 6% ÙÔ ›‰ÈÔ SMC Ô˘ ‚Ú¤ıËΠÛÙÔ ·È‰› Û 45% ÙˆÓ ÌÂÙ·Ê¿ÛÂˆÓ (ηڢfiÙ˘Ô˜ ·Ù¤Ú· ·ÛıÂÓ‹ ¡Ô 1: 46,XY[94]/47,XY+marker[6]). ∂›Û˘, ÛÙË ÌËÙ¤Ú· ÙÔ˘ ÂÌ‚Ú‡Ô˘ ¡Ô 16 ÙÔ SMC ˘‹Ú¯Â Û fiϘ ÙȘ ÌÂÙ·Ê¿ÛÂȘ Ô˘ ·Ó·Ï‡ıËÎ·Ó (47,ÃÃ+marker[100]). ªÂÙ¿ ÙË ÌÂϤÙË Ì ÙË Ì¤ıÔ‰Ô ‚·Ê‹˜ ÔÏfiÎÏËÚˆÓ ÙˆÓ ¯ÚˆÌÔۈ̿وÓ, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ DNA ·ÓȯÓÂ˘Ù‹ ÁÈ· ÙÔ ¯ÚˆÌfiۈ̷ 15, ‰È·ÈÛÙÒıËΠfiÙÈ ÙÔ SMC Û fiϘ ÙȘ ÂÚÈÙÒÛÂȘ ‹Ù·Ó ÙÌ‹Ì· ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15 (∂ÈÎfiÓ· 2).

∂ÈÎfiÓ· 1. ªÂÙ·Ê¿ÛÂȘ ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ ¡Ô 1 (·ÚÈÛÙÂÚ¿) Ì ÌÈÎÚÔ‡ ÌÂÁ¤ıÔ˘˜ SMC(15) Î·È ¡Ô 14 (‰ÂÍÈ¿) Ì ÌÂÁ¿ÏÔ˘ ÌÂÁ¤ıÔ˘˜ SMC(15) (Ù·Èӛ˜ G).

297

ªÂÚÈ΋ ÙÚÈۈ̛· 15: Ê·ÈÓfiÙ˘Ô˜-ÁÔÓfiÙ˘Ô˜

¶›Ó·Î·˜ 1. ∞ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ ÙˆÓ ·ÛıÂÓÒÓ Ì ÎÏ·ÛÈ΋ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË Î·È ÊıÔÚ›˙ÔÓÙ· in situ ˘‚ÚȉÈÛÌfi (FISH) ¡Ô

∫˘ÙÙ·ÚÔÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË

FISH

1 2 3 4 5 6 7 8 9 10

46,XX[55]/47,XX+mar[45] ÔÈÎÔÁÂÓ¤˜* 47,XX+mar[100] de novo 47,XY+mar[100] de novo 47,XÀ+mar[100] de novo 47,XÀ+mar[100] de novo 47,XX+mar[100] de novo 47,XX+mar[100] de novo 47,XY+mar[100] de novo 47,XX+mar[100] de novo 47,XX+mar[100] de novo

11

47,XX+mar[100] de novo

12

47,XX+mar[100] de novo

13

47,XX+mar[100] de novo

14

47,XX+mar[100] de novo

15

47,XY+mar[100] de novo

16

47,XX+mar[100] ÔÈÎÔÁÂÓ¤˜**

ish der (15)(wcp15+) ish der (15)(wcp15+) ish der (15)(wcp15+) ish der (15)(wcp15+) ish der (15)(wcp15+) ish der (15)(wcp15+) ish der (15)(wcp15+) ish der (15)(wcp15+) ish der (15)(wcp15+) ish der(15)(wcp15+),ish(15q11.2q13) (SNRPNx3,15qtelx2) ish der(15)(wcp15+),ish(15q11.2q13) (SNRPNx2,15qtelx2) ish der(15)(wcp15+),ish(15q11.2q13) (SNRPNx2,15qtelx2) ish der(15)(wcp15+),ish(15q11.2q13) (SNRPNx2,15qtelx2) ish der(15)(wcp15+),ish(15q11.2q13) (SNRPNx3,15qtelx2) ish der(15)(wcp15+),ish(15q11.2q13) (SNRPNx2,15qtelx2) ish der(15)(wcp15+),ish(15q11.2q13) (SNRPNx2,15qtelx2)

* ∫·Ú˘fiÙ˘Ô˜ ·Ù¤Ú·: 46,XY[94]/47,XY+marker[6] ** K·Ú˘fiÙ˘Ô˜ ÌËÙ¤Ú·˜: 47,XX+marker[100]

™ÙȘ ÂÚÈÙÒÛÂȘ ¡Ô 10 ¤ˆ˜ ¡Ô 16 Ì ÌÂÁ¿ÏÔ˘ ÌÂÁ¤ıÔ˘˜ SMC(15), ÌÂϤÙË Ì ÙÔÓ ·ÓȯÓÂ˘Ù‹ SNRPN/15qtel ÁÈ· ¤ÏÂÁ¯Ô ‡·Ú͢ Ù˘ ÎÚ›ÛÈÌ˘ ÂÚÈÔ¯‹˜ PWS/AS, ·ÔÎ¿Ï˘„ 3 Û‹Ì·Ù· ˘‚ÚȉÈÛÌÔ‡ ÁÈ· ÙÔ ÁÔÓ›‰ÈÔ SNRPN ÛÙÔ˘˜ ·ÛıÂÓ›˜ ¡Ô 10 Î·È ¡Ô 14. ™Â η̛· ·fi ÙȘ ÂÚÈÙÒÛÂȘ Ô˘ ÌÂÏÂÙ‹ıËηÓ, ‰ÂÓ ·ÓȯÓ‡ÙËÎ·Ó ÛÙÔ SMC(15) Û‹Ì·Ù· ˘‚ÚȉÈÛÌÔ‡ ÁÈ· ÙÔ ÙÂÏÔÌÂÚ›‰ÈÔ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15 (15qtel)

(EÈÎfiÓ· 3). ™ÙÔ˘˜ ·ÛıÂÓ›˜ ¡Ô 10 Î·È ¡Ô 14, Ë ·Ó¿Ï˘ÛË DNRPs ÂȂ‚·›ˆÛ ÙËÓ ·ÚÔ˘Û›· ÙÚÈÒÓ ·ÏÏËÏfiÌÔÚÊˆÓ Î·È ¤‰ÂÈÍ fiÙÈ ÙÔ SMC ‹Ù·Ó ÌËÙÚÈ΋˜ ÚÔ¤Ï¢Û˘ (∂ÈÎfiÓ· 4). ŒÏÂÁ¯Ô˜ ÙÔ˘ ÚÔÙ‡Ô˘ ÌÂı˘Ï›ˆÛ˘ ÛÙÔ˘˜ ‰‡Ô ·˘ÙÔ‡˜ ·ÛıÂÓ›˜ Ì ªSPCR ¤‰ÂÈÍÂ Ê˘ÛÈÔÏÔÁÈÎfi ÚfiÙ˘Ô ÌÂı˘Ï›ˆÛ˘, ·ÔÎÏ›ÔÓÙ·˜ ÙËÓ Èı·ÓfiÙËÙ· Û˘Ó‰ÚfiÌÔ˘ PWS Î·È ÛÙ· ‰‡Ô ·È‰È¿ (∂ÈÎfiÓ· 5).

∂ÈÎfiÓ· 2. ªÂÙ¿Ê·ÛË ·fi ÙËÓ ·ÛıÂÓ‹ ¡Ô 10 ÌÂÙ¿ ·fi ÌÂϤÙË Ì FISH (̤ıÔ‰Ô˜ ‚·Ê‹˜ ÔÏfiÎÏËÚÔ˘ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 15). ∆Ô SMC(15) Î·È Ù· ‰‡Ô Ê˘ÛÈÔÏÔÁÈο ¯ÚˆÌÔÛÒÌ·Ù· 15 ¤¯Ô˘Ó ‚·Ê› Ì ÙÔÓ ·ÓȯÓÂ˘Ù‹ (Ú¿ÛÈÓÔ ¯ÚÒÌ·).

∂ÈÎfiÓ· 3. ªÂÙ¿Ê·ÛË ·fi ÙËÓ ·ÛıÂÓ‹ ¡Ô 14 ÌÂÙ¿ ·fi ÌÂϤÙË Ì FISH Ì ÙÔ˘˜ ·ÓȯÓÂ˘Ù¤˜ SNRPN (ÎfiÎÎÈÓÔ Û‹Ì· ) Î·È 15qtel (Ú¿ÛÈÓÔ Û‹Ì·). ¶·È‰È·ÙÚÈ΋ 2006;69:294-300

298

∞. ∫ÔÏȷϤÍË Î·È Û˘Ó.

∂ÈÎfiÓ· 4. ∞ÔÙÂϤÛÌ·Ù· ·Ó¿Ï˘Û˘ DNRP Ù˘ ÔÏ˘ÌÔÚÊÈ΋˜ ı¤Û˘ D15S97 ÛÙËÓ ·ÛıÂÓ‹ ¡Ô 10. ¶·Ú·ÙËÚÂ›Ù·È Ë ·ÚÔ˘Û›· ÙÚÈÒÓ ·ÏÏËÏfiÌÔÚÊˆÓ (‰‡Ô ÌËÙÚÈ΋˜ Î·È ¤Ó· ·ÙÚÈ΋˜ ÚÔ¤Ï¢Û˘) ÛÙÔ ·È‰› (F: ·Ù¤Ú·˜, C: ·È‰›, M: ÌËÙ¤Ú·).

™˘˙‹ÙËÛË ¶·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ù· Â˘Ú‹Ì·Ù· ·fi ÙË ÁÂÓÂÙÈ΋ ÌÂϤÙË 16 ÂÚÈÙÒÛÂˆÓ SMCs Ô˘ ‰È·ÁÓÒÛÙËÎ·Ó Ì ÎÏ·ÛÈ΋ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÛÙÔ ∂ÚÁ·ÛÙ‹ÚÈÔ π·ÙÚÈ΋˜ °ÂÓÂÙÈ΋˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ Î·Ù¿ ÙËÓ ÂÓÙ·ÂÙ›· 20002005. ™Â fiϘ ÙȘ ÂÚÈÙÒÛÂȘ, Ë Ù·˘ÙÔÔ›ËÛË Ù˘ ¯ÚˆÌÔÛˆÌÈ΋˜ ÙÔ˘˜ ÚÔ¤Ï¢Û˘ ¤ÁÈÓ Ì ÙËÓ Ù¯ÓÈ΋ FISH. ∂›Ó·È ÂӉȷʤÚÔÓ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Û 10 ·fi ÙȘ 16 ÂÚÈÙÒÛÂȘ Ù˘ ÌÂϤÙ˘, Ë ËÏÈΛ· Ù˘ ÌËÙ¤Ú·˜ ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 35 ÂÙÒÓ, ÂÔ̤ӈ˜ Â›Ó·È Èı·Ófi fiÙÈ Ë ÂÌÊ¿ÓÈÛË ÙˆÓ SMC(15)s ÔÊ›ÏÂÙ·È Û ·ÙÂÏ‹ ‰È·¯ˆÚÈÛÌfi ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÛÙË Ì›ˆÛË π, Ô˘ ¤¯ÂÈ Û˘Ó‰Âı› Ì ·˘ÍË̤ÓË ËÏÈΛ· Ù˘ ÌËÙ¤Ú·˜ (3,13). ¢Âη٤ÛÛÂÚ· SMC(15)s (¡Ô 2 ¤ˆ˜ ¡Ô 15) ‹Ù·Ó de novo, ÂÓÒ Û ‰‡Ô ÂÚÈÙÒÛÂȘ ‹Ù·Ó ÔÈÎÔÁÂÓ‹. ™˘ÁÎÂÎÚÈ̤ӷ, fiÛÔÓ ·ÊÔÚ¿ ÛÙËÓ ·ÛıÂÓ‹ ¡Ô 1, Ë ÔÔ›· ·Ú·¤ÌÊıËΠÏfiÁˆ ÌÈÎÚÔ‡ ‚·ıÌÔ‡ ÓÔËÙÈ΋˜ ˘ÛÙ¤ÚËÛ˘ Î·È ‰È·Ù·Ú·¯ÒÓ ÙÔ˘ ÏfiÁÔ˘, ÙÔ SMC(15) ‰È·ÈÛÙÒıËΠ۠ÌÈÎÚfi ÔÛÔÛÙfi (6%) Î·È ÛÙÔÓ Ê·ÈÓÔÙ˘Èο Ê˘ÛÈÔÏÔÁÈÎfi ·Ù¤Ú· Ù˘. ∂Ô̤ӈ˜, Ô ‹ÈÔ˜ ·ıÔÏÔÁÈÎfi˜ Ê·ÈÓfiÙ˘Ô˜ Ù˘ ·ÛıÂÓÔ‡˜ Èı·ÓÒ˜ Ó· ÔÊ›ÏÂÙ·È ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ÙÔ˘ SMC(15) (45%) Û ۯ¤ÛË Ì ÙÔÓ Ê˘ÛÈÔÏÔÁÈο Ê·ÈÓÔÙ˘ÈÎfi ·Ù¤Ú· Ù˘. ™ÙÔ ¤Ì‚Ú˘Ô ¡Ô 16 Ì SMC(15) ÛÙÔ 100% ÙˆÓ ÌÂÙ·Ê¿ÛÂˆÓ Ô˘ ÌÂÏÂÙ‹ıËηÓ, ·fi ÙËÓ ·Ó¿Ï˘ÛË ÙÔ˘ ηڢÔÙ‡Ô˘ ÙˆÓ ÁÔÓ¤ˆÓ ‰È·ÈÛÙÒıËΠfiÙÈ Ë ÌËÙ¤Ú· ¤ÊÂÚ ÙÔ ›‰ÈÔ SMC(15) Û fiϘ ÙȘ ÌÂÙ·Ê¿ÛÂȘ Ô˘ ÌÂÏÂÙ‹ıËηÓ. √È ÁÔÓ›˜ ·ÔÊ¿ÛÈÛ·Ó Ó· Û˘Ó¯ÈÛÙ› Ë Î‡ËÛË Î·È ÁÂÓÓ‹ıËΠʷÈÓÔÙ˘Èο Ê˘ÛÈÔÏÔÁÈÎfi ÓÂÔÁÓfi. ¶·È‰È·ÙÚÈ΋ 2006;69:294-300

∂ÈÎfiÓ· 5. ∞ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘ Ì MSPCR. C3: º˘ÛÈÔÏÔÁÈÎfi˜ Ì¿ÚÙ˘Ú·˜: ·ÚÔ˘Û›· ‰‡Ô ÚÔ˚fiÓÙˆÓ, ÂÓfi˜ ·fi ÙÔ ÌËÙÚÈ΋˜ ÚÔ¤Ï¢Û˘ ·ÏÏËÏfiÌÔÚÊÔ (ÌÂÁ¤ıÔ˘˜ 174bp) Î·È ÂÓfi˜ ·fi ÙÔ ·ÙÚÈ΋˜ ÚÔ¤Ï¢Û˘ ·ÏÏËÏfiÌÔÚÊÔ (ÌÂÁ¤ıÔ˘˜ 100bp) (Ê˘ÛÈÔÏÔÁÈÎfi ÚfiÙ˘Ô ÌÂı˘Ï›ˆÛ˘), C1: M¿ÚÙ˘Ú·˜ Ì PWS: ·ÚÔ˘Û›· ÌfiÓÔ ÚÔ˚fiÓÙÔ˜ ·fi ÙÔ ÌËÙÚÈÎfi ·ÏÏËÏfiÌÔÚÊÔ (ÌÂÁ¤ıÔ˘˜ 174bp), C2: M¿ÚÙ˘Ú·˜ Ì AS: ·ÚÔ˘Û›· ÌfiÓÔ ÚÔ˚fiÓÙÔ˜ ·fi ÙÔ ·ÙÚÈÎfi ·ÏÏËÏfiÌÔÚÊÔ (ÌÂÁ¤ıÔ˘˜ 100bp), 5 Î·È 6: ∞ÛıÂÓ‹˜ ¡Ô 10 (Ê˘ÛÈÔÏÔÁÈÎfi ÚfiÙ˘Ô ÌÂı˘Ï›ˆÛ˘), 7 Î·È 8: ∞ÛıÂÓ‹˜ ¡Ô 14 (Ê˘ÛÈÔÏÔÁÈÎfi ÚfiÙ˘Ô ÌÂı˘Ï›ˆÛ˘).

™ÙÔ˘˜ ·ÛıÂÓ›˜ No 2 ¤ˆ˜ ¡Ô 9 ·ÓȯÓ‡ÙËΠÌÈÎÚÔ‡ ÌÂÁ¤ıÔ˘˜ SMC(15). ∆· ·È‰È¿ ·˘Ù¿, fiˆ˜ Î·È ÔÈ ÂÚÈÙÒÛÂȘ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·, ·ÚÔ˘Û›·˙·Ó ‹ÈÔ ÎÏÈÓÈÎfi Ê·ÈÓfiÙ˘Ô ¯ˆÚ›˜ ‰˘ÛÌÔÚÊÈο ¯·Ú·ÎÙËÚÈÛÙÈο, Ì ÌÂÙÚ›Ô˘ ‚·ıÌÔ‡ ÓÔËÙÈ΋ ˘ÛÙ¤ÚËÛË Î·È Ì·ıËÛȷο ÚÔ‚Ï‹Ì·Ù·. ∞˘Ùfi Èı·ÓÒ˜ ÔÊ›ÏÂÙ·È ÛÙËÓ ‡·ÚÍË ÛÙÔ SMC ›Ù ÌË ÏÂÈÙÔ˘ÚÁÈÎÒÓ ÁÔÓȉ›ˆÓ, ›Ù ÁÔÓȉ›ˆÓ Ô˘ ‰ÂÓ ÌÂÙ·ÁÚ¿ÊÔÓÙ·È (6). ™‡Ìʈӷ Ì ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ, ÌÂÁ¿ÏÔ˘ ÌÂÁ¤ıÔ˘˜ SMC(15)s Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙÔ ÁÔÓ›‰ÈÔ SNRPN, ·Ú·ÙËÚÔ‡ÓÙ·È Û ÔÛÔÛÙfi 35% ÙˆÓ ·ÛıÂÓÒÓ Ì PWS, ÂÓÒ Ë ‰È·›ÛÙˆÛ‹ ÙÔ˘˜ ÛÙÔÓ ÚÔÁÂÓÓËÙÈÎfi ¤ÏÂÁ¯Ô ¤¯ÂÈ Î›Ó‰˘ÓÔ 12% ÂÌÊ¿ÓÈÛ˘ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÏfiÁˆ UPD Ô˘ ÚÔ·ÙÂÈ ·fi ÙËÓ Ù˘¯·›· ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ·ÙÚÈÎÔ‡ ·ÏÏËÏfiÌÔÚÊÔ˘ (6-11). °È· ÙÔÓ ÏfiÁÔ ·˘Ùfi, Ù· ÌÂÁ¿ÏÔ˘ ÌÂÁ¤ıÔ˘˜ SMC(15)s ÛÙ· ÂÚÈÛÙ·ÙÈο ¡Ô 10 ¤ˆ˜ ¡Ô 16 Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ ‰ÈÂÚ¢ӋıËÎ·Ó ÂÚ·ÈÙ¤Úˆ Ì FISH, Ì ÙÔÓ ·ÓȯÓÂ˘Ù‹ SNRPN/15qtel, ÛÙËÓ ÎÚ›ÛÈÌË ÂÚÈÔ¯‹ ÙˆÓ Û˘Ó‰ÚfiÌˆÓ PWS/AS. ∞fi ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜, ÔÈ ¡Ô 10 Î·È ¡Ô 14 ›¯·Ó ·ÚfiÌÔÈ· ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›·, ˘ÔÙÔÓ›· Î·È Û·ÛÌÔ‡˜ Î·È ·Ú·¤ÌÊıËÎ·Ó ÁÈ· ΢ÙÙ·ÚÔÁÂÓÂÙÈÎfi ¤ÏÂÁ¯Ô Û ËÏÈΛ· 8 Î·È 8ó ÌËÓÒÓ, ·ÓÙ›ÛÙÔȯ·. ∏ ·ÚÔ˘Û›· ÙÚÈÒÓ ·ÓÙÈÁÚ¿ÊˆÓ Ù˘ ÎÚ›ÛÈÌ˘ ÂÚÈÔ¯‹˜ PWS/AS ÛÙ· ‰‡Ô ·˘Ù¿ ·È‰È¿ ÂȂ‚·ÈÒıËÎÂ Î·È Ì ·Ó¿Ï˘ÛË DNRPs. ∂ÈϤÔÓ, Ë ÌÂϤÙË ¤‰ÂÈÍ fiÙÈ ÙÔ SMC(15) ‹Ù·Ó Î·È ÛÙȘ ‰‡Ô ÂÚÈÙÒÛÂȘ ÌËÙÚÈ΋˜ ÚÔ¤Ï¢Û˘,

299

ªÂÚÈ΋ ÙÚÈۈ̛· 15: Ê·ÈÓfiÙ˘Ô˜-ÁÔÓfiÙ˘Ô˜

·ÏÏ¿ ÌÂϤÙË ÙÔ˘ ÚÔÙ‡Ô˘ ÌÂı˘Ï›ˆÛ˘ ·¤ÎÏÂÈÛ ÙËÓ Èı·ÓfiÙËÙ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ PWS. ™ÙËÓ ÂÚ›ÙˆÛË ¡Ô 15 ÙÔ ÌÂÁ¿ÏÔ SMC(15) ‹Ù·Ó de novo, ·ÓȯÓ‡ÙËΠÛÙÔÓ ÚÔÁÂÓÓËÙÈÎfi ¤ÏÂÁ¯Ô Î·È ‰ÂÓ ÂÚÈ›¯Â ÙËÓ ÎÚ›ÛÈÌË ÂÚÈÔ¯‹ ÙˆÓ Û˘Ó‰ÚfiÌˆÓ PW/AS. ∂Âȉ‹, fï˜, ‰ÂÓ ‹Ù·Ó ‰˘Ó·Ùfi Ó· ·ÔÎÏÂÈÛÙ› οÔÈÔ˜ ·ıÔÏÔÁÈÎfi˜ Ê·ÈÓfiÙ˘Ô˜ Î·È Ó· ÚÔÛ‰ÈÔÚÈÛÙ› Ë ‚·Ú‡ÙËÙ¿ ÙÔ˘, ÔÈ ÁÔÓ›˜ ·ÔÊ¿ÛÈÛ·Ó ÙË ‰È·ÎÔ‹ Ù˘ ·ËÛ˘. π‰È·›ÙÂÚÔ ÂӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙ÂÈ Ë ·ÛıÂÓ‹˜ ¡Ô 11, Ë ÔÔ›· ·Ú·¤ÌÊıËΠÁÈ· ΢ÙÙ·ÚÔÁÂÓÂÙÈÎfi ¤ÏÂÁ¯Ô Û ËÏÈΛ· 2 ÂÙÒÓ ÏfiÁˆ ‹ÈˆÓ ‰˘ÛÌÔÚÊÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ, fiˆ˜ ÌÈÎÚ‹ ̇ÙË, ‚ÏÂÊ·ÚfiÙˆÛË, Ì·ÎÚ‡ Ê›ÏÙÚÔ Î·È Û˘ÌÙÒÌ·Ù· ȉÈÔ·ıÔ‡˜ ·ÚıÚ›Ùȉ·˜ Ì ÂȉÂÈÓÔ‡ÌÂÓË ÎÏÈÓÈ΋ ÂÈÎfiÓ·. ¶·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë ·ÈÙÈÔÏÔÁ›· Ù˘ ȉÈÔ·ıÔ‡˜ ·ÚıÚ›Ùȉ·˜ ·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙË, Û Û¿ÓȘ ÂÚÈÙÒÛÂȘ Ë ÓfiÛÔ˜ ¤¯ÂÈ Û˘Ó‰Âı› Ì ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜, fiˆ˜ ÂÏÏ›ÌÌ·Ù· ÙÔ˘ Ì·ÎÚÔ‡ ÛΤÏÔ˘˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 22 (22q-). øÛÙfiÛÔ, fiÛÔ Â›Ì·ÛÙ Û ı¤ÛË Ó· ÁÓˆÚ›˙Ô˘ÌÂ, Â›Ó·È Ë ÚÒÙË ÊÔÚ¿ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·ÚÔ˘Û›· SMC(15) (14-19). ™˘ÌÂÚ·ÛÌ·ÙÈο, Ë ·Ó›¯Ó¢ÛË de novo ‹ oÈÎÔÁÂÓÔ‡˜ SMC(15) ··ÈÙ› ÂÚ·ÈÙ¤Úˆ ‰ÈÂÚ‡ÓËÛË Ì ÌÔÚÈ·Îfi ΢ÙÙ·ÚÔÁÂÓÂÙÈÎfi Î·È ÌÔÚÈ·Îfi ¤ÏÂÁ¯Ô, Ì ÛÎÔfi Ó· ÚÔÛ‰ÈÔÚÈÛÙ› Ë ÁÔÓȉȷ΋ Û‡ÛÙ·ÛË ÙÔ˘ ˘ÂÚ¿ÚÈıÌÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜, Ó· Ù·˘ÙÔÔÈËı› Ë ÁÔÓÂ˚΋ ÚԤϢÛË Î·È Ó· ·ÔÎÏÂÈÛÙ› Ë ÌÔÓÔÁÔÓÂ˚΋ ‰Èۈ̛· (UPD). √ ÔÏÔÎÏËڈ̤ÓÔ˜ ·˘Ùfi˜ ÁÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ Â›Ó·È ··Ú·›ÙËÙÔ˜ ÁÈ· ÙÔÓ Û˘Û¯ÂÙÈÛÌfi ÁÔÓÔÙ‡Ô˘ Ê·ÈÓÔÙ‡Ô˘, ·ÏÏ¿ Î·È ÁÈ· ÙË ÁÂÓÂÙÈ΋ ηıÔ‰‹ÁËÛË ÙˆÓ ÔÈÎÔÁÂÓÂÈÒÓ.

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¶∂ƒπ§∏æ∏ ∞¶√ ∆∏ µπµ§π√°ƒ∞ºπ∞

ABSTRACT

Child abuse registration, fetal growth, and preterm birth: a population based study N. Spencer, A. Wallace, R. Sundrum, C. Bacchus, S. Logan Objectives: To study the relation of intra-uterine growth and gestational age with child protection

registration in a 20 year whole population birth cohort.

Setting: West Sussex area of England.

Study design: Retrospective whole population birth cohort. Outcomes: Child protection registration; individual categories of registration-sexual abuse, physical abuse, emotional abuse, and neglect.

Population and participants: 119,771 infants born in West Sussex between January 1983 and December 2001 with complete data including birth weight, gestational age, maternal age, and postcode.

Results: In all categories of registration a linear trend was noted such that the lower the birth weight z score the higher the likelihood of child protection registration. Similar trends were noted for gestational age. All these trends were robust to adjustment for maternal age and socioeconomic status.

Conclusions: The results of this study suggest that lower levels of fetal growth and shorter gestational duration are associated with increased likelihood of child protection registration in all categories including sexual abuse independent of maternal age or socioeconomic status. This study does not permit comment on whether poor fetal growth or preterm birth predispose to child abuse and neglect or the association arises because they share a common pathway.

J Epidemiol Community Health, 2006;60(4):337-340.

™¯ÔÏÈ·ÛÌfi˜ ÙÔ˘ ¿ÚıÚÔ˘ ·ÎÔÏÔ˘ı› ÛÙËÓ ÂfiÌÂÓË ÛÂÏ›‰· Editorial commentary on next page

¶·È‰È·ÙÚÈ΋ 2006;69:294-300

™Ã√§π√ ∞¶√ ∆∏ ™À¡∆∞•∏

EDITORIAL COMMENTARY

N. Spencer The opportunity to study the association of child abuse with fetal growth and preterm birth arose out of our work with this unique population-based child health data set that combines high quality information on all children born with addresses in the West Sussex region of England and child protection registration data for the same region (1). Our review of the published literature suggested that the association was disputed and a previous review of casecontrol studies had concluded that the association was spurious (2). However, two population-based studies (3,4) reported an association with low birth weight after adjustment for confounding variables.

Previously reported studies had a number of limitations. They studied all forms of abuse combined, which precluded any analysis of how different forms of abuse might differ in their association with pregnancy outcomes. In addition, the studies that analysed the association of abuse with low birth weight (<2500 g) failed to distinguish between low birth weight resulting from impaired fetal growth or short gestation.

The West Sussex data set, collected over 19 years, was large enough to allow us to overcome some of these limitations. The paper reports on the association of fetal growth, expressed as birth weight z scores categorised into five groups, and gestational age, categorised into three groups, with registration for child abuse and neglect in four categories, physical, emotional, sexual, and neglect. The data set also enabled us to adjust for maternal age and an areabased measure of socioeconomic status, both of which are known to be associated with pregnancy outcomes and risk of abuse.

The results showed that, for all categories of abuse, there was a linear trend such that the lower the category of fetal growth and gestation the higher the risk of abuse. Neglect showed the strongest linear trend by both fetal growth and gestation and sexual abuse the weakest (1).

What can we conclude from these results?

There can be little doubt that impaired fetal growth and short gestation are associated with subsequent risk of child protection registration independent of maternal age or socioeconomic status. It also seems that the risk of registration increases with increasing impairment of fetal growth and decreasing gestational age - in other words, they demonstrate a “dose-response” relationship.

In common with all studies of child abuse and neglect, we relied on child protection registration to identify children who had been abused. Misclassification bias is likely to arise because some children who have been abused may not come to the atten-

tion of the services and may not be registered. It is important to be aware of this limitation when interpreting the study findings.

In practical terms, these results might help to alert practitioners to higher levels of risk among infants born small and/or early but there remain questions that our findings do not answer. Do impaired fetal growth and short gestation predispose to abuse and neglect? Is the association causal? Although the data are effectively longitudinal with birth weight, gestational age, maternal age and socioeconomic status data collected before the outcome of interest, we cannot say from the findings whether the relationship is causal or the result of a shared pathway related to an unmeasured maternal or paternal characteristic. Growth impaired and preterm infants are known to have developmental problems (5) that might make them more difficult to manage.

They are also more likely to be separated from their mothers in the neonatal period and suffer illness and hospital admission in early infancy. These factors may increase the vulnerability of these infants to abuse and neglect. Alternatively, the association may not be causal but may result from other family characteristics that predispose to both poor pregnancy outcomes and abuse and neglect.

In summary, we think that, despite unanswered questions about the association, our study provides the most comprehensive data so far on the links between pregnancy outcome and child abuse. Future research should focus on eliminating other family characteristics as the underlying cause of this association and understanding the mechanisms by which the pathways from pregnancy outcome to abuse operate.

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School of Health and Social Studies and Warwick Medical School, University of Warwick, Coventry, UK Correspondence: E-mail: n.j.spencer@warwick.ac.uk

References 1. N. Spencer, A. Wallace, R. Sundrum, C. Bacchus, S. Logan. Child abuse registration, fetal growth, and preterm birth: a population based study. J Epidemiol Community Health 2006;60:337-340.

2. Leventhal JM. Risk factors for child abuse: methodologic standards in case-control studies.

Pediatrics 1981;68:684-690.

3. Needell B, Barth RP. Infants entering foster care compared with other infants using birth status indicators. Child Abuse Negl 1998;22:1179-1187.

4. Sidebotham P, Heron J; ALSPAC Study Team. Child maltreatment in the “children of the nineties”: the role of the child. Child Abuse Negl 2003;27:337-352.

5. Pharoah PO, Stephenson CJ, Cooke RW, Stephenson RC. Clinical and sub-clinical deficits at 8 years in a geographically defined cohort of low birthweight infants. Arch Dis Child 1994;70:264-270. ¶·È‰È·ÙÚÈ΋ 2006;69:301

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∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏

CASE REPORT

∞ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ Û¯ÂÙÈ˙fiÌÂÓÔ Ì ÙÔÓ Èfi Epstein-Barr. ¶ÂÚÈÁÚ·Ê‹ ‰‡Ô ÂÚÈÙÒÛÂˆÓ Ì ‰È·ÊÔÚÂÙÈ΋ ÎÏÈÓÈ΋ ¤Î‚·ÛË ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ∞ÈÌ·ÙÔÏÔÁ›·˜/√ÁÎÔÏÔÁ›·˜, ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ ∫Ú‹Ù˘ AÏÏËÏÔÁÚ·Ê›·: ª·Ú›· ∫·ÏÌ·ÓÙ‹ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ∞ÈÌ·ÙÔÏÔÁ›·˜/√ÁÎÔÏÔÁ›·˜ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ ∫Ú‹Ù˘ ∆.£. 2208, ∆.∫. 710 03, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ E-mail: pedhem@med.uoc.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 28-01-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 28-03-2006

∂. ¢ËÏ·Ó¿˜, µ. ¢·ÓËÏ¿ÙÔ˘, ∞. ∫·ÌÔ˘Ú¿Î˘, ∂.-∞. ª·ÚοÎË, ∂. ™ÙÂȷοÎË, ª. ∫·ÏÌ·ÓÙ‹

¶ÂÚ›ÏË„Ë: ∆Ô ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ Â›Ó·È Û¿ÓÈ· ÔÈÎÔÁÂÓ‹˜ ‹ ‰Â˘ÙÂÚÔ·ı‹˜ Û˘ÛÙËÌ·ÙÈ΋ ‰È·Ù·Ú·¯‹ Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ˘ÂÚ‰Ú·ÛÙËÚÈfiÙËÙ· ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ, ∆- Î·È ¡∫-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. √ Èfi˜ Epstein-Barr (EBV) ıˆÚÂ›Ù·È Ô Î‡ÚÈÔ˜ ÂÎÏ˘ÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜. ¶ÂÚÈÁÚ¿ÊÔÓÙ·È ‰‡Ô ¿ÚÚÂÓ˜ ·ÛıÂÓ›˜, ËÏÈΛ·˜ 10 Î·È 3,5 ÂÙÒÓ, Ì ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ Û¯ÂÙÈ˙fiÌÂÓÔ Ì EBV Î·È ‰È·ÊÔÚÂÙÈ΋ ÎÏÈÓÈ΋ ÔÚ›· Î·È ¤Î‚·ÛË. √ ÚÒÙÔ˜ ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·Û ·Ó΢ÙÙ·ÚÔÂÓ›·, Ë·ÙÔÛÏËÓÔÌÂÁ·Ï›·, ÏÂÌÊ·‰ÂÓÔ¿ıÂÈ· Î·È ÛÙËÓ ÔÚ›· ÚÔÛ‚ÔÏ‹ ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ‰È¿¯˘ÙË ÂÓ‰·ÁÁÂȷ΋ ‹ÍË, ˘ÂÚÊÂÚÚÈÙÈÓ·ÈÌ›·, ˘Ô˚Óˆ‰ÔÁÔÓ·ÈÌ›· Î·È ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·. ∏ ‰È¿ÁÓˆÛË Ù¤ıËΠ̠ÛÏËÓÂÎÙÔÌ‹ Î·È ÈÛÙÔ·ıÔÏÔÁÈ΋ ÂͤٷÛË ÙÔ˘ ÛÏËÓfi˜, ÂÓÒ Â·ÓÂÈÏËÌ̤Ó˜ ÔÛÙÂÔÌ˘ÂÏÈΤ˜ ‚ÈÔ„›Â˜ ‹Ù·Ó ·ÚÓËÙÈΤ˜ ÁÈ· ·ÈÌÔÊ·ÁÔ΢ÙÙ¿ÚˆÛË. ŒÏ·‚ ıÂÚ·›· Û‡Ìʈӷ Ì ÙÔ ¯ËÌÂÈÔıÂÚ·¢ÙÈÎfi ÚˆÙfiÎÔÏÏÔ HLH-94. §fiÁˆ ÔÏÏ·ÏÒÓ ˘ÔÙÚÔÒÓ, ¤ÁÈÓ ·ÏÏÔÁÂÓ‹˜ ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ Ì ÌÔÈÚ·›· ηٿÏËÍË. √ ‰Â‡ÙÂÚÔ˜ ·ÛıÂÓ‹˜ ÂÌÊ·Ó›ÛÙËΠ̠ÂÈÎfiÓ· Û˘Ó‰ÚfiÌÔ˘ ÏÔÈÌÒ‰Ô˘˜ ÌÔÓÔ˘Ú‹ÓˆÛ˘, ·Ó·ÈÌ›·, Ô˘‰ÂÙÂÚÔÂÓ›·, ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Î·È ˘ÂÚÊÂÚÚÈÙÈÓ·ÈÌ›·. ∏ ‰È¿ÁÓˆÛË Ù¤ıËΠ¤ÁηÈÚ· Ì ÔÛÙÂÔÌ˘ÂÏÈ΋ ‚ÈÔ„›·. ŒÏ·‚ ıÂÚ·›· Û‡Ìʈӷ Ì ÙÔ ¯ËÌÂÈÔıÂÚ·¢ÙÈÎfi ÚˆÙfiÎÔÏÏÔ HLH-94 Î·È Â›Ó·È ÂχıÂÚÔ˜ ÓfiÛÔ˘ 12 Ì‹Ó˜ ÌÂÙ¿ ÙÔ Ù¤ÏÔ˜ Ù˘ ıÂÚ·›·˜. ∆Ô ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ Â›Ó·È ÎÏÈÓÈο ÂÙÂÚÔÁÂÓ‹˜ ÓfiÛÔ˜ Ì ˘„ËÏ‹ ıÓËÙfiÙËÙ·. ∏ ‰È¿ÁÓˆÛË Î·È Ë ‰È¿ÎÚÈÛË ·Ó¿ÌÂÛ· ÛÙËÓ ÔÈÎÔÁÂÓ‹ Î·È ÙË ‰Â˘ÙÂÚÔ·ı‹ ÌÔÚÊ‹ Â›Ó·È ‰‡ÛÎÔϘ. √È ·ÛıÂÓ›˜ ÌÔÚ› Ó· ÏËÚÔ‡Ó ¤Ó· ‹ ÂÚÈÛÛfiÙÂÚ· ÎÚÈÙ‹ÚÈ· fi„ÈÌ· ηٿ ÙËÓ ÔÚ›· Ù˘ ÓfiÛÔ˘. ∆ÔÓ›˙ÂÙ·È fiÙÈ ·ÎfiÌË Î·È Â› ·Ô˘Û›·˜ ÙˆÓ ‰È·ÁÓˆÛÙÈÎÒÓ ÎÚÈÙËÚ›ˆÓ, Ú¤ÂÈ Ó· ·Ú¯›˙ÂÈ ÂÁη›Úˆ˜ Ë ıÂÚ·›· Ì ‚¿ÛË ‰ÈÂıÓ‹ ÚˆÙfiÎÔÏÏ· Ô˘ ÂÚȤ¯Ô˘Ó ÂÙÔÔÛ›‰Ë, ÂÊfiÛÔÓ ˘¿Ú¯ÂÈ ÈÛ¯˘Ú‹ ÎÏÈÓÈ΋ ˘Ô„›·. ∆¤ÏÔ˜, Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ ÂӉ›ÎÓ˘Ù·È Û ÂÚÈÙÒÛÂȘ ÔÈÎÔÁÂÓÔ‡˜ ‹ ·ÓıÂÎÙÈÎÔ‡ ‰Â˘ÙÂÚÔ·ıÔ‡˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘. §¤ÍÂȘ ÎÏÂȉȿ: ∞ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ, Èfi˜ Epstein-Barr, ·È‰È¿, ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ.

Haemophagocytic syndrome related to Epstein-Barr virus.

Report of two cases with different clinical outcome Paediatric Clinic of Haematology/Oncology, University Hospital of Heraklion, Crete Correspondence: Maria Kalmanti Paediatric Clinic of Haematology/Oncology University Hospital of Heraklion, Crete PO Box 2208, 710 03, Heraklion, Crete E-mail: pedhem@med.uoc.gr Date of submission: 28-01-2005 Date of approval: 28-03-2006

¶·È‰È·ÙÚÈ΋ 2006;69:302-309

E. Dilanas, V. Danilatou, A. Kambourakis, E.-A. Markaki, E. Stiakaki, M. Kalmanti

Abstract: Haemophagocytic syndrome is a rare familial or secondary systemic disorder, which is characterized by excessive function of macrophages and T- and NK-lymphocytes. The major triggering factor is the Epstein-Barr virus (EBV). The described cases are of two male patients, aged 10 and 3.5 years respectively with EBV-associated haemophagocytic syndrome, with different course and outcome. The first patient presented with cytopenia, hepatospenomegaly and lymphadenopathy, and later developed CNS involvement, disseminated intravascular coagulopathy, hyperferritinaemia, hypofibrinogenaemia, and hypertriglyceridaemia. Diagnosis was documented by splenectomy and splenic histopathological examination, while serial bone marrow biopsies were negative for haemophagocytosis. He was treated in accordance with the HLH-94 protocol. Allogeneic bone marrow transplantation was performed four years after diagnosis, because of recurrent relapses, but the outcome was fatal. The second patient presented with infectious mononucleosis syndrome, anaemia, neutropenia, hypertriglyceridaemia and hyperferritinaemia. Diagnosis was established early by bone marrow biopsy. He was treated according to the HLH-94 protocol and is free of disease 12 months after completion of therapy. Haemophagocytic syndrome is a clinically heterogenous disease with high mortality. Diagnosis and distinction between familial and secondary disease can be difficult.

One or more criteria may be met late in the course of the disease, but it is stressed that when that there

303

πÔÁÂÓ¤˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ ÛÙ· ·È‰È¿

is strong clinical suspicion therapy should be initiated despite absence of diagnostic criteria. Bone marrow transplantation is indicated in cases of familial or refractory secondary haemophagocytic syndrome.

Key words: Haemophagocytic syndrome, Epstein-Barr virus, children, bone marrow transplantation.

™˘ÓÙÔÌÔÁڷʛ˜ ∞º™ ¢∂¶ π∞™ ∫¡™ §ª ªª√ √¡¶ √∞™ º§À¡ EBV PCR CT MRI

∞ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ ¢È¿¯˘ÙË ÂÓ‰·ÁÁÂȷ΋ ‹ÍË πÔÁÂÓ¤˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ ∫ÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ· §ÔÈÌ҉˘ ÌÔÓÔ˘Ú‹ÓˆÛË ªÂÙ·ÌfiÛ¯Â˘ÛË Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ √ÛÊ˘ÔÓˆÙÈ·›· ·Ú·Î¤ÓÙËÛË √ÈÎÔÁÂÓ¤˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ º˘ÏÔÛ‡Ó‰ÂÙË ÏÂÌÊÔ¸ÂÚÏ·ÛÙÈ΋ ÓfiÛÔ˜ πfi˜ Epstein-Barr Polymerase chain reaction Computerized tomography Magnetic resonance imaging

∂ÈÛ·ÁˆÁ‹ To ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ (∞º™), ÁÓˆÛÙfi Î·È ˆ˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈ΋ ÏÂÌÊÔ˚ÛÙÈÔ΢ÙÙ¿ÚˆÛË, ÂÚÈÏ·Ì‚¿ÓÂÈ ¤Ó· ¢ڇ Ê¿ÛÌ· ÎÏËÚÔÓÔÌÈÎÒÓ Î·È Â›ÎÙËÙˆÓ ÓÔÛËÌ¿ÙˆÓ, Ô˘ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi ‰È·Ù·Ú·¯‹ Ù˘ ·ÓÔÛÔÏÔÁÈ΋˜ Ú‡ıÌÈÛ˘. ÷ڷÎÙËÚ›˙ÂÙ·È ·fi ˘ÚÂÙfi, Ë·ÙÔÛÏËÓÔÌÂÁ·Ï›·, ÏÂÌÊ·‰ÂÓÔ¿ıÂÈ·, ÂÍ¿ÓıËÌ·, ÚÔÛ‚ÔÏ‹ ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (∫¡™), ΢ÙÙ·ÚÔÂӛ˜ Û ≥2 ·ÈÌÔÔÈËÙÈΤ˜ ÛÂÈÚ¤˜, ‰˘ÛÏÈȉ·ÈÌ›· Î·È ‰È·Ù·Ú·¯¤˜ ‹Í˘. ∏ ÓfiÛÔ˜ Û·ÓÈfiÙÂÚ· Â›Ó·È ÎÏËÚÔÓÔÌÈ΋ (ÔÈÎÔÁÂÓ¤˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ √∞™), ÂÌÊ·Ó›˙ÂÙ·È Û˘Ó‹ıˆ˜ Û ¿ÙÔÌ· ËÏÈΛ·˜ <2 ÂÙÒÓ, Ì ıÂÙÈÎfi ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi, ÁÔÓÂ˚΋ Û˘ÁÁ¤ÓÂÈ· ÂÍ ·›Ì·ÙÔ˜ Î·È ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ˘„ËÏ‹ ıÓËÙfiÙËÙ·. ∏ Û˘ÓËı¤ÛÙÂÚË ÌÔÚÊ‹ Â›Ó·È Ë ‰Â˘ÙÂÚÔ·ı‹˜ ÌÂÙ·ÏÔÈÌ҉˘ ‹ Û¯ÂÙÈ˙fiÌÂÓË Ì ηÎÔ‹ıÂȘ (΢ڛˆ˜ ÏÂÌÊÒÌ·Ù·) Î·È ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù· (1). √ Èfi˜ Epstein-Barr (EBV) ıˆÚÂ›Ù·È Ô Î‡ÚÈÔ˜ ÂÎÏ˘ÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÙÔ˘ ‰Â˘ÙÂÚÔ·ıÔ‡˜ ∞º™. ¶ÚÔÛ‚¿ÏÏÂÈ Ù· ∆- Î·È NK-ÏÂÌÊÔ·ÙÙ·Ú·, ÚÔηÏÒÓÙ·˜ ÙÔÓ ·ÓÂͤÏÂÁÎÙÔ ÌÔÓÔ‹ ÔÏÈÁÔÎψÓÈÎfi ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙÔ˘˜ Î·È Û˘ÓÔ‰fi ˘ÂÚ·Ú·ÁˆÁ‹ ΢ÙÙ·ÚÔÎÈÓÒÓ (2). ∏ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÂÌÊ·Ó›˙ÂÙ·È Û ·È‰È¿ Î·È ÂÊ‹‚Ô˘˜ ÌÂ Ê˘ÛÈÔÏÔÁÈ΋ ·ÓÔÛÔÏÔÁÈ΋ ·ÓÙ·fiÎÚÈÛË (2). ¶ÂÚÈÁÚ¿ÊÔÓÙ·È ‰‡Ô ÂÚÈÙÒÛÂȘ ·È‰ÈÒÓ

ËÏÈΛ·˜ 10 Î·È 3,5 ÂÙÒÓ Ì ∞º™ Û¯ÂÙÈ˙fiÌÂÓÔ Ì ÙÔÓ Èfi EBV (EBV-∞º™) Ì ‰È·ÊÔÚÂÙÈ΋ ÎÏÈÓÈ΋ ÔÚ›· Î·È ¤Î‚·ÛË.

¶ÂÚÈÁÚ·Ê‹ ÂÚÈÙÒÛÂˆÓ ¶ÂÚ›ÙˆÛË ÚÒÙË ∞ÁfiÚÈ ËÏÈΛ·˜ 10 ÂÙÒÓ ÚÔÛ‹Ïı ÛÙËÓ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ∞ÈÌ·ÙÔÏÔÁ›·˜/√ÁÎÔÏÔÁ›·˜ Ì ˘„ËÏfi ˘ÚÂÙfi Î·È Ú›ÁÔ˜ (̤¯ÚÈ 40ÔC), ‰È¿ÚÎÂÈ·˜ 5 ËÌÂÚÒÓ. ∂›¯Â ÓÔÛËÏ¢Ù› ÁÈ· ¿ÁÓˆÛÙ˘ ·ÈÙÈÔÏÔÁ›·˜ ˘ÔÙÚÔÈ¿˙ÔÓÙ· ÂÌ‡ÚÂÙ· Î·È ‰ÈfiÁΈÛË ‹·ÙÔ˜ Î·È ÛÏËÓfi˜, ÙÔ˘˜ ÚÔËÁÔ‡ÌÂÓÔ˘˜ 10 Ì‹Ó˜. ∞fi ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠ‰ÈfiÁΈÛË ‹·ÙÔ˜ Î·È ÛÏËÓfi˜ (2 cm Î·È 10 cm οو ·fi ÙÔ Ï¢ÚÈÎfi ÙfiÍÔ, ·ÓÙ›ÛÙÔȯ·) Î·È ·fi ÙÔÓ ·Ú¯ÈÎfi ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô Ï¢ÎÔÂÓ›·, Ô˘‰ÂÙÂÚÔÂÓ›·, ·Ó·ÈÌ›·, ‹È· ıÚÔÌ‚ÔÂÓ›·, ·˘ÍË̤ӷ Ë·ÙÈο ¤Ó˙˘Ì· Î·È LDH (¶›Ó·Î·˜ 1). √ ÏÂÙÔÌÂÚ‹˜ ¤ÏÂÁ¯Ô˜ ÁÈ· ÏÔÈÌÒ‰ÂȘ ·Ú¿ÁÔÓÙ˜, ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù· Î·È Î·ÎÔ‹ıÂȘ, Ô˘ ÂÚÈÂÏ¿Ì‚·Ó ηÏÏȤÚÁÂȘ ‚ÈÔÏÔÁÈÎÒÓ ˘ÁÚÒÓ, ·ÓÔÛÔÛÊ·ÈÚ›Ó˜ ÔÚÔ‡, ÔÛÊ˘ÔÓˆÙÈ·›· ·Ú·Î¤ÓÙËÛË (√¡¶), Ì˘ÂÏfiÁÚ·ÌÌ·, ÔÛÙÂÔÌ˘ÂÏÈ΋ ‚ÈÔ„›· Î·È ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô, ‹Ù·Ó ·ÚÓËÙÈÎfi˜, ÏËÓ ÙÔ˘ ÔÚÔÏÔÁÈÎÔ‡ ÂϤÁ¯Ô˘ Ô˘ ¤‰ÂÈÍ ÔÍ›· Ïԛ̈ÍË ·fi Èfi EBV. ∏ PCR ÁÈ· ÙÔÓ EBV ÛÙ· ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ‹Ù·Ó ıÂÙÈ΋. √ ¤ÏÂÁ¯Ô˜ ÙˆÓ ÏÂÌÊÔ΢ÙÙ·ÚÈÎÒÓ ÏËı˘ÛÌÒÓ ¤‰ÂÈÍ ·Ó·ÛÙÚÔÊ‹ Ù˘ ·Ó·ÏÔÁ›·˜ CD4+/CD8+ (0,76). ∞Ú¯Èο ¯ÔÚËÁ‹ıËΠÂÌÂÈÚÈ΋ ‰ÈÏ‹ ·ÓÙÈ‚ÈÔÙÈ΋ ·ÁˆÁ‹. ∆Ë 15Ë Ë̤ڷ Ù˘ ÓfiÛÔ˘ ÂÌÊ¿ÓÈÛ ÁÂÓÈÎÂ˘Ì¤ÓÔ ÎËÏȉԂϷÙȉ҉˜, ÂÙ¯ÂÈ҉˜ ÂÍ¿ÓıËÌ·, ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ· Î·È Âȉ›ӈÛË Ù˘ ·Ó΢ÙÙ·ÚÔÂÓ›·˜ Ì ‰È·Ù·Ú·¯¤˜ ‹Í˘ (¶›Ó·Î·˜ 1). ∆Ô 18Ô 24ˆÚÔ Ù˘ ÓfiÛÔ˘ ÂȉÂÈÓÒıËÎÂ Ë ÁÂÓÈ΋ ÙÔ˘ ηٿÛÙ·ÛË, Ì ¤ÓÙÔÓË ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·, ÂÒ‰˘ÓË Ë·ÙÔÌÂÁ·Ï›·, ÂÈÎfiÓ· ηٷÏËÍ›·˜, ‰È¿¯˘ÙË ÂÓ‰·ÁÁÂȷ΋ ‹ÍË (¢∂¶) (¶›Ó·Î·˜ 1) Î·È ÎÏÈÓÈÎÔ-·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù· Ó¢ÌÔÓ›·˜ Ì ·ÌÊÔÙÂÚfiÏ¢ÚË Ï¢ÚÈÙÈ΋ Î·È ·ÛÎÈÙÈ΋ ¶·È‰È·ÙÚÈ΋ 2006;69:302-309

304

∂. ¢ËÏ·Ó¿˜ Î·È Û˘Ó.

¶›Ó·Î·˜ 1. ∂ÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ù˘ ÚÒÙ˘ ÂÚ›ÙˆÛ˘ ∏̤ڷ ÓfiÛÔ˘ Ht (%) Hb (g/dl) §Â˘Î¿/Ìl ∞∞¶/Ìl ∞ª¶ x103/Ìl ¢∂∫ (%) SGOT (U/L) SGPT (U/L) LDH (U/L) ÁGT (U/L) ∆°∫ (mg/dl) ºÂÚÚÈÙ›ÓË (ng/ml) PT (sec) aPTT (sec) πÓˆ‰ÔÁfiÓÔ (mg/dl) D-dimers (Ìg/ml) ATIII (%)

5Ë

15Ë

18Ë

23Ë

30‹

37Ë

57Ë

87Ë

32,2 10,5 1400 750 143

28,7 9,5 1500 500 165 0,76 101 49 768 47

25,5 8,8 1700 500 52

29,7 9,9 1600 480 54 0,55 99 89 1187

25,5 8,7 1200 500 73

34,4 11,3 21700 15400 93,2

33,6 11,5 13600 4000 367

18815 13,2 44,3 238 9,79

464 458 2598 206 396 12813 12,4 30 233 1,71

228 62 1165 241 289

6403 14,3 37,9 96 3,91

23,2 7,7 1600 490 7 0,53 17 25 1976 315 781 33354 13 48,4 155 2,46

181 55 546 87

17699 15,2 44,9 181 5,27

552 100 1243 52 115 19,1 58,6 109 8,87 58,2

133 73 1876 262

22,1 76,5 152 32,8 71

∞∞¶: ∞fiÏ˘ÙÔ˜ ·ÚÈıÌfi˜ ÔÏ˘ÌÔÚÊÔ‡ÚËÓˆÓ ∞ª¶: ∞ÈÌÔÂÙ¿ÏÈ· ∆°∫: ∆ÚÈÁÏ˘ÎÂÚ›‰È·

Û˘ÏÏÔÁ‹. ÃÔÚËÁ‹ıËÎ·Ó ÎÔÚÙÈÎÔÂȉ‹ ÁÈ· ÙËÓ ·Ó·ÎÔ‡ÊÈÛË ÙˆÓ ·Ó·Ó¢ÛÙÈÎÒÓ Û˘Ìو̿وÓ, ηıÒ˜ Î·È Û˘Ì˘Îӈ̤ӷ ÂÚ˘ıÚ¿, ÊÚ¤ÛÎÔ Î·Ù„˘Á̤ÓÔ Ï¿ÛÌ· Î·È ·ÓÙÈıÚÔÌ‚›ÓË πππ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·Ó·ÈÌ›·˜ Î·È Ù˘ ¢∂¶. √ ΢ÙÙ·ÚÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ˘ÏÈÎÔ‡ ·fi ÙËÓ ·Ú·Î¤ÓÙËÛË Ù˘ Ï¢ÚÈÙÈ΋˜ Î·È ·ÛÎÈÙÈ΋˜ Û˘ÏÏÔÁ‹˜ ‹Ù·Ó ·ÚÓËÙÈÎfi˜ ÁÈ· ηÎÔ‹ıÂÈ·. ∆ËÓ 23Ë Ë̤ڷ Ù˘ ÓfiÛÔ˘, ÂÓÒ Ô ·ÛıÂÓ‹˜ Û˘Ó¤¯È˙ ӷ ˘Ú¤ÛÛÂÈ Ì ÂÈÎfiÓ· ·Ó΢ÙÙ·ÚÔÂÓ›·˜, ¢∂¶ Î·È ·‡ÍËÛ˘ ÙˆÓ ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ (¶›Ó·Î·˜ 1), ·ÚÔ˘Û›·Û ÂÂÈÛfi‰ÈÔ ÁÂÓÈÎÂ˘Ì¤ÓˆÓ ÙÔÓÈÎÔÎÏÔÓÈÎÒÓ Û·ÛÌÒÓ. ∆Ô Ì˘ÂÏfiÁÚ·ÌÌ· Î·È Ë ÔÛÙÂÔÌ˘ÂÏÈ΋ ‚ÈÔ„›· Â·Ó·Ï‹ÊıËηÓ, ·ÏÏ¿ ‰ÂÓ ‹Ù·Ó ‰È·ÁÓˆÛÙÈο. ¢ÈÂÓÂÚÁ‹ıËΠ‚˘ıÔÛÎfiËÛË, √¡¶ Î·È CT ÂÁÎÂÊ¿ÏÔ˘ ‰›¯ˆ˜ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ÃÔÚËÁ‹ıËΠ·Î˘ÎÏÔ‚›ÚË Ì ÙËÓ ˘fiÓÔÈ· ÂÁÎÂÊ·Ï›Ùȉ·˜ Î·È Ê·ÈÓ˘ÙÔ˝ÓË ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ Û·ÛÌÒÓ. ∆ËÓ 30‹ Ë̤ڷ Ù˘ ÓfiÛÔ˘ ¤ÁÈÓ ÂÚ¢ÓËÙÈ΋ Ï··ÚÔÙÔÌ›·, ÛΈÏËÎÔÂȉÂÎÙÔÌ‹ Î·È ‚ÈÔ„›· ÏÂÌÊ·‰¤ÓˆÓ, ¯ˆÚ›˜ Â˘Ú‹Ì·Ù· ηÎÔ‹ıÂÈ·˜. ∆Ô Ì˘ÂÏfiÁÚ·ÌÌ· Î·È Ë ÔÛÙÂÔÌ˘ÂÏÈ΋ ‚ÈÔ„›· ÙËÓ 37Ë Ë̤ڷ Ù˘ ÓfiÛÔ˘ ¤‰ÂÈÍ·Ó ˘ÔÏ·ÛÙÈÎfi Ì˘ÂÏfi Î·È Ô ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ˘ÂÚÊÂÚÚÈÙÈÓ·ÈÌ›· Î·È ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·. ∆ËÓ 57Ë Ë̤ڷ (¶›Ó·Î·˜ 1) ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ÓfiÛÔ˘, Ì ÙËÓ ˘fiÓÔÈ· ÙÔ˘ ∞º™, ¤ÁÈÓ ÛÏËÓÂÎÙÔÌ‹ Î·È ‚ÈÔ„›· ‹·ÙÔ˜. ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· ‹Ù·Ó ÔÌ·Ï‹ Î·È Ô ·ÛıÂÓ‹˜ ·Ú¤ÌÂÈÓ Âχı¶·È‰È·ÙÚÈ΋ 2006;69:302-309

ÚÔ˜ Û˘Ìو̿وÓ. ∏ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË ÙÔ˘ ÛÏËÓfi˜ ‹Ù·Ó Û˘Ì‚·Ù‹ Ì ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ.

O ·ÛıÂÓ‹˜ Â·ÓÂÌÊ¿ÓÈÛ ˘ÚÂÙfi, Ï‹ı·ÚÁÔ, ‰È¿¯˘ÙÔ ÎËÏȉԂϷÙȉ҉˜ ÂÍ¿ÓıËÌ·, ÙÚ·¯ËÏÈ΋ ÏÂÌÊ·‰ÂÓÔ¿ıÂÈ·, ˘ÔÓ·ÙÚÈ·ÈÌ›·, ¢∂¶ Î·È ·˘ÍË̤ӷ Ë·ÙÈο ¤Ó˙˘Ì·, LDH Î·È ÙÚÈÁÏ˘ÎÂÚ›‰È· ÙËÓ 87Ë Ë̤ڷ Ù˘ ÓfiÛÔ˘ (¶›Ó·Î·˜ 1). ™ÙË Ê¿ÛË ·˘Ù‹ ¤Ï·‚ ıÂÚ·¢ÙÈο Á-ÛÊ·ÈÚ›ÓË. §fiÁˆ Âȉ›ӈÛ˘ Ù˘ ·Ó·Ó¢ÛÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ‰È·ÛˆÏËÓÒıËÎÂ Î·È ÌÂٷʤÚıËΠÛÙË ÌÔÓ¿‰· ÂÓÙ·ÙÈ΋˜ ıÂÚ·›·˜. ∏ Â·Ó¿ÏË„Ë Ù˘ ÔÛÙÂÔÌ˘ÂÏÈ΋˜ ‚ÈÔ„›·˜ ‹Ù·Ó Û˘Ì‚·Ù‹ Ì ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ Î·È Ë ÂͤٷÛË ÙÔ˘ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô˘ ˘ÁÚÔ‡ (∂¡À) ¯ˆÚ›˜ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ÕÌÂÛ· ÍÂΛÓËÛ ¯ËÌÂÈÔıÂÚ·›· Û‡Ìʈӷ Ì ÙÔ ÚˆÙfiÎÔÏÏÔ HLH94 (∂ÈÎfiÓ· 1), ÙÔ ÔÔ›Ô ÂÚÈÏ·Ì‚¿ÓÂÈ ÂÓ‰ÔÊϤ‚È· ÂÙÔÔÛ›‰Ë Î·È ‰ÂÍ·ÌÂı·˙fiÓË. ∏ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂÚ·›· ‹Ù·Ó ¿ÌÂÛË Î·È ı·̷ÙÈ΋. ™ÙË Û˘Ó¤¯ÂÈ·, fï˜, ·ÚÔ˘Û›·Û ÔÏÏ·Ϥ˜ ˘ÔÙÚÔ¤˜ Ì ˘ÚÂÙfi, ·Ó·Ó¢ÛÙÈ΋ ‰˘Û¯¤ÚÂÈ·, Ó¢ÌÔÓ›·, ÂÍ¿ÓıËÌ· Î·È ·‡ÍËÛË ÙˆÓ ‚ÈÔ¯ËÌÈÎÒÓ ‰ÂÈÎÙÒÓ Ù˘ ÓfiÛÔ˘ (ÊÂÚÚÈÙ›Ó˘, ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ, ÙÚÈÁÏ˘ÎÂÚȉ›ˆÓ). √ ¤ÏÂÁ¯Ô˜ ÁÈ· HLA Û˘Ì‚·ÙfiÙËÙ· ÙÔ˘ ·‰ÂÏÊÔ‡ ÙÔ˘ ·¤‚Ë ·ÚÓËÙÈÎfi˜ Î·È Ë ·Ó·˙‹ÙËÛË ÌË Û˘ÁÁÂÓÔ‡˜ Û˘Ì‚·ÙÔ‡ ‰fiÙË ‰ÂÓ ·Ó¤‰ÂÈÍ ·fiÏ˘Ù· Û˘Ì‚·Ùfi ‰fiÙË. ∏ ¡∫ ‰Ú·ÛÙËÚÈfiÙËÙ· ‹Ù·Ó ÂÏ·Ùو̤ÓË. ∆· Â›‰· ÙÔ˘ ‰È·Ï˘ÙÔ‡ ˘Ô‰Ô¯¤· Ù˘ IL-2 (sCD25) ÛÙÔÓ ÔÚfi ÚÈÓ ÙËÓ ¤Ó·ÚÍË ıÂÚ·›·˜

305

πÔÁÂÓ¤˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ ÛÙ· ·È‰È¿

£∂ƒ∞¶∂π∞ ∂º√¢√À

£∂ƒ∞¶∂π∞ ™À¡∆∏ƒ∏™∏™/µª∆

ËÌÂÚ‹ÛÈ· ¯ÔÚ‹ÁËÛË ‰ÂÍ·ÌÂı·˙fiÓ˘

ÒÛÂȘ ‰ÂÍ·ÌÂı·˙fiÓ˘

10 mg

DEXA mg/m2

5 mg 2,5 mg 1,25 mg

VP-16 CSA IT MTX 1

2

3

4

5

6

7

8

9

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

‚‰ÔÌ¿‰Â˜

39 40 41 42 43 44 45 46 47 48 49 50 51 52

∂ÈÎfiÓ· 1. ÃËÌÂÈÔıÂÚ·¢ÙÈÎfi ÚˆÙfiÎÔÏÏÔ HLH-94 (4).

DEXA: ¢ÂÍ·ÌÂı·˙fiÓË. ∫·Ù¿ ÙË ıÂÚ·›· ÂÊfi‰Ô˘ ¯ÔÚËÁÂ›Ù·È ‰ÂÍ·ÌÂı·˙fiÓË Ì ·Ú¯È΋ ‰fiÛË 10 mg/m2 Î·È ˘Ô‰ÈÏ·ÛÈ·ÛÌfi Ù˘ ‰fiÛ˘ ·Ó¿ ‰‡Ô ‚‰ÔÌ¿‰Â˜. ™ÙË ıÂÚ·›· Û˘ÓÙ‹ÚËÛ˘ ¯ÔÚËÁÔ‡ÓÙ·È ÒÛÂȘ ‰ÂÍ·ÌÂı·˙fiÓ˘ ÙˆÓ 10 mg/m2 ÙÚÈ‹ÌÂÚ˘ ‰È¿ÚÎÂÈ·˜ οı ‰Â‡ÙÂÚË Â‚‰ÔÌ¿‰·.

VP-16: ∂ÙÔÔÛ›‰Ë 150 mg/m2 ÂÓ‰ÔÊÏ‚›ˆ˜. ∫·Ù¿ ÙËÓ ÂÊfi‰Ô ¯ÔÚËÁÔ‡ÓÙ·È ÙȘ ‰‡Ô ÚÒÙ˜ ‚‰ÔÌ¿‰Â˜ ‰‡Ô ‰fiÛÂȘ Î·È ÙȘ ÂfiÌÂÓ˜ Ì›· ‰fiÛË ·Ó¿ ‚‰ÔÌ¿‰·. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Û˘ÓÙ‹ÚËÛ˘ ¯ÔÚËÁÂ›Ù·È Ì›· ‰fiÛË Î¿ı ‰‡Ô ‚‰ÔÌ¿‰Â˜.

CSA: ∫˘ÎÏÔÛÔÚ›ÓË. ∫·ıËÌÂÚÈÓ‹ ¯ÔÚ‹ÁËÛË ÛÙË Ê¿ÛË Û˘ÓÙ‹ÚËÛ˘. π∆ ª∆Ã: ∂Ó‰ÔÚ·¯È·›· ÌÂıÔÙÚÂÍ¿ÙË Î·Ù¿ ÙËÓ ·Ú¯‹ Ù˘ 3˘, 4˘, 5˘ Î·È 6˘ ‚‰ÔÌ¿‰·˜ Ù˘ ıÂÚ·›·˜ ÂÊfi‰Ô˘, Â¿Ó ˘¿Ú¯Ô˘Ó ÂÍÂÏÈÛÛfiÌÂÓ· Ó¢ÚÔÏÔÁÈο Û˘ÌÙÒÌ·Ù· ‹ ÛÙ·ıÂÚ¿ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù· ÛÙÔ ∂¡À. ∞ÛıÂÓ›˜ ¯ˆÚ›˜ √∞™ ‹ ÂÓÂÚÁ‹ ÓfiÛÔ, ÚÔÙ›ÓÂÙ·È Ó· ‰È·ÎfiÙÔ˘Ó ÙË ıÂÚ·›· ÌÂÙ¿ ÙËÓ ÔÏÔÎÏ‹ÚˆÛË Ù˘ ‰fiÛ˘ ÂÊfi‰Ô˘ Î·È Ó· ÙËÓ ÍÂÎÈÓÔ‡Ó ÂÎ Ó¤Ô˘ Û ÂÚ›ÙˆÛË ·Ó·˙ˆ‡ÚˆÛ˘.

BMT: ªÂÙ·ÌfiÛ¯Â˘ÛË Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ê¿Û˘ Û˘ÓÙ‹ÚËÛ˘.

‹Ù·Ó 2460 U/ml, ÂÓÒ ÙËÓ 57Ë Â‚‰ÔÌ¿‰· ıÂÚ·›·˜ ÂÏ·ÙÙÒıËÎ·Ó Û 1348 IU/ml (º∆ <1000 IU/ml). ¢ÂÓ ‚Ú¤ıËΠÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ ÂÚÊÔÚ›Ó˘, ÂÓÒ Ô ÁÔÓȉȷÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· Ê˘ÏÔÛ‡Ó‰ÂÙË ÏÂÌÊÔ¸ÂÚÏ·ÛÙÈ΋ ÓfiÛÔ (º§À¡) ¤‰ÂÈÍÂ Ê˘ÛÈÔÏÔÁÈÎfi ÔÏ˘ÌÔÚÊÈÛÌfi. ªÂ ÙË Û˘ÌÏ‹ÚˆÛË 62 ‚‰ÔÌ¿‰ˆÓ ıÂÚ·›·˜, Ô˘ ÂÚÈÂÏ¿Ì‚·Ó ÒÛÂȘ ÂÙÔÔÛ›‰Ë˜, ‰ÂÍ·ÌÂı·˙fiÓ˘ Î·È Î˘ÎÏÔÛÔÚ›ÓË (∂ÈÎfiÓ· 1), ·ÔÊ·Û›ÛÙËÎÂ Ë ‰È·ÎÔ‹ ÙÔ˘ ÚˆÙÔÎfiÏÏÔ˘ ÁÈ·Ù› ‰ÂÓ ·ÓÙ·ÔÎÚÈÓfiÙ·Ó ÛÙË ıÂÚ·›· Î·È Â›¯Â ·Ó·Ù‡ÍÂÈ ˘ÂÚ‚ÔÏÈ΋ Ê·Ú̷΢ÙÈ΋ ÙÔÍÈÎfiÙËÙ· (ÈÓÛÔ˘ÏÈÓÔÂÍ·ÚÙÒÌÂÓÔ˜ ۷ί·Ú҉˘ ‰È·‚‹Ù˘, ηٷÚÚ¿ÎÙ˘, ·¯˘Û·ÚΛ·, ÂÚÈÔÚÈÛÙÈ΋ Ó¢ÌÔÓÔ¿ıÂÈ·, ˘¤ÚÙ·ÛË, ÔÛÙÂÔÂÓ›·, ¤ÎÙˆÛË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜, ÏÈˆÌ¿ÙˆÛË ÌÂÛÔıˆÚ·Î›Ô˘), ÂÈϤÔÓ ‰Â, Ô Î›Ó‰˘ÓÔ˜ ·Ó¿Ù˘Í˘ ‰Â˘ÙÂÚÔ·ıÔ‡˜ ηÎÔ‹ıÂÈ·˜ ‹Ù·Ó ·˘ÍË̤ÓÔ˜ Î·È Ë ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂÚ·›· ‰ÂÓ ‹Ù·Ó ÈηÓÔÔÈËÙÈ΋. ∂Ó·ÏÏ·ÎÙÈο ¯ÔÚËÁ‹ıËΠÚ‰ÓÈ˙fiÓË, ‚ÈÓÎÚÈÛÙ›ÓË, ‰ÔÍÔÚÔ˘-

ÌÈΛÓË Î·È Î˘ÎÏÔʈÛÊ·Ì›‰Ë, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ‰ÂÓ ˘‹Ú¯Â ‰È·ı¤ÛÈÌÔ˜ Û˘Ì‚·Ùfi˜ ‰fiÙ˘ ÁÈ· ·ÏÏÔÁÂÓ‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ (ªª√). ¢¤Î· ̤Ú˜ ·ÚÁfiÙÂÚ· ˘ÔÙÚÔ›·ÛÂ Î·È ·fi ÙfiÙ ¯ÔÚËÁ‹ıËÎ·Ó ÌÔÓÔ‹ÌÂÚ˜ ÒÛÂȘ ‰ÂÍ·ÌÂı·˙fiÓ˘ ‚‰ÔÌ·‰È·›·, Ì ÛÙ·‰È·Î‹ Ì›ˆÛË Ù˘ ‰fiÛ˘ Î·È ‰È·ÎÔ‹ ÌÂÙ¿ ¤Ó· ¯ÚfiÓÔ. ∆ÚÂȘ Ì‹Ó˜ ÌÂÙ¿ ÙË ‰È·ÎÔ‹ Ù˘ ıÂÚ·›·˜ Ô ·ÛıÂÓ‹˜ ˘ÔÙÚÔ›·ÛÂ Î·È Â·Ó·¯ÔÚËÁ‹ıËΠÂÙÔÔÛ›‰Ë Î·È ‰ÂÍ·ÌÂı·˙fiÓË. ∏ ÓfiÛÔ˜ ·ÚÔ˘Û›·Û ‡ÊÂÛË ÁÈ· ‰È¿ÛÙËÌ· 40 ËÌÂÚÒÓ ¯ˆÚ›˜ ¿ÏÏË ıÂÚ·›·, ÔfiÙ ·ÚÔ˘Û›·Û Ӥ· ˘ÔÙÚÔ‹ Ô˘ ·ÓÙ·ÔÎÚ›ıËΠ۠ÌÔÓÔ‹ÌÂÚË ¯ÔÚ‹ÁËÛË ‰ÂÍ·ÌÂı·˙fiÓ˘ (10 mg/m2). §fiÁˆ Ù˘ ÂÎÛÂÛËÌ·Ṳ̂Ó˘ ÙÔÍÈÎfiÙËÙ·˜ ·fi ÙËÓ ·Ú·ÙÂٷ̤ÓË ¯Ú‹ÛË ÙˆÓ ÎÔÚÙÈÎÔÂȉÒÓ Î·Ù¿ ÙËÓ ·Ó·ÌÔÓ‹ ·Ó‡ÚÂÛ˘ ‰fiÙË ÁÈ· ·ÏÏÔÁÂÓ‹ ªª√, ¯ÔÚËÁ‹ıËΠÌÂÚηÙÔÔ˘Ú›ÓË. ∆¤ÛÛÂÚ· ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂÚ·›·˜ ‚Ú¤ıËΠÛÙË ‰ÈÂıÓ‹ ÙÚ¿Â˙· ‰ÔÙÒÓ ÌÂÚÈο Û˘Ì‚·Ùfi˜ ‰fiÙ˘ Î·È ÏfiÁˆ ˘ÔÙÚÔÈ¿˙Ô˘Û·˜ ¶·È‰È·ÙÚÈ΋ 2006;69:302-309

306

∂. ¢ËÏ·Ó¿˜ Î·È Û˘Ó.

¶›Ó·Î·˜ 2. ∂ÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ù˘ ‰Â‡ÙÂÚ˘ ÂÚ›ÙˆÛ˘ ∏̤ڷ ÓfiÛÔ˘ Hb (g/dl) Ht (%) §Â˘Î¿/Ìl ∞∞¶/Ìl ∞ª¶ x103/Ìl SGOT (U/L) SGPT (U/L) ÁGT (U/L) LDH (mg/dl) ∆°∫ (mg/dl) ºÂÚÚÈÙ›ÓË (ng/ml) PT (sec) aPTT (sec) πÓˆ‰ÔÁfiÓÔ (mg/dl) D-dimers (Ìg/ml) ATIII (%)

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8,5 24,2 11200 2700 197000 163 126 210 879

7,8 23 11000 1900 231000 153 102 167 1055 719 2341 12,7 35,5 341

7 21,1 7100 400 162000 123 62 92 1109 308

8,9 27,7 13200 1800 287000 108 105 44 611 448 1282 13 99,6 307 3,4 134

11,7 35,1 7700 1500 423000 38 43 11 250 65 266 14,6 41 272

12,6 34,2 246 3,1 124

∞∞¶: ∞fiÏ˘ÙÔ˜ ·ÚÈıÌfi˜ ÔÏ˘ÌÔÚÊÔ‡ÚËÓˆÓ ∞ª¶: ∞ÈÌÔÂÙ¿ÏÈ· ∆°∫: ∆ÚÈÁÏ˘ÎÂÚ›‰È·

Î·È ·ÓıÂÎÙÈ΋˜ ÓfiÛÔ˘ ·Ú·¤ÌÊıËΠÁÈ· ·ÏÏÔÁÂÓ‹ ªª√. √ ·ÛıÂÓ‹˜ η٤ÏËÍ ÛÙË ÌÔÓ¿‰· ÌÂÙ·ÌfiÛ¯Â˘Û˘ ·fi Û‡Ó‰ÚÔÌÔ ÙÚȯÔÂȉÈ΋˜ ‰È·Ê˘Á‹˜ Û ¤‰·ÊÔ˜ ÛËÙÈ΋˜ ηٷÏËÍ›·˜ ·fi ·Û¤ÚÁÈÏÏÔ Î·È ÔÍ›· ÓfiÛÔ ÌÔۯ‡̷ÙÔ˜ ηٿ ÍÂÓÈÛÙ‹. ¶ÂÚ›ÙˆÛË ‰Â‡ÙÂÚË ÀÁȤ˜, ηٿ ÙÔ ·ÚÂÏıfiÓ, ¿ÚÚÂÓ Ó‹ÈÔ ËÏÈΛ·˜ 3,5 ÂÙÒÓ ·Ú·¤ÌÊıËΠ·fi ‰Â˘ÙÂÚÔ‚¿ıÌÈÔ ÓÔÛÔÎÔÌÂ›Ô ÁÈ· ˘ÚÂÙfi ‰È¿ÚÎÂÈ·˜ 20 ËÌÂÚÒÓ. ∞fi ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠÂËÚ·Ṳ̂ÓË ÁÂÓÈ΋ ηٿÛÙ·ÛË, ˆ¯ÚfiÙËÙ·, ‰ÈfiÁΈÛË ÔÌ¿‰·˜ ÙÚ·¯ËÏÈÎÒÓ ÏÂÌÊ·‰¤ÓˆÓ (‰È·Ì¤ÙÚÔ˘ 4 cm), ˘Ò‰Ë˜ ·Ì˘Á‰·Ï›Ùȉ· Î·È ‰ÈfiÁΈÛË ‹·ÙÔ˜ Î·È ÛÏËÓfi˜ (5 cm Î·È 9 cm οو ·fi ÙÔ Ï¢ÚÈÎfi ÙfiÍÔ, ·ÓÙ›ÛÙÔȯ·). ∞fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ‰È·ÈÛÙÒıËΠ·Ó·ÈÌ›·, ·ÓÔÛÔÏÔÁÈο ‰ÈÂÁÂṲ́ӷ ÏÂÌÊÔ·ÙÙ·Ú· Ù‡Ô˘ ÏÔÈÌÒ‰Ô˘˜ ÌÔÓÔ˘Ú‹ÓˆÛ˘ ÛÙÔ Â›¯ÚÈÛÌ· ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ Î·È ·‡ÍËÛË ÙˆÓ ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ (¶›Ó·Î·˜ 2), ÂÓÒ Ô ÈÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍ ÔÍ›· Ïԛ̈ÍË ·fi EBV. √ ¤ÏÂÁ¯Ô˜ Ì PCR ÂȂ‚·›ˆÛ ÙËÓ ‡·ÚÍË ÁÔÓȉÈÒÌ·ÙÔ˜ ÙÔ˘ ÈÔ‡ ÛÙ· ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜. ∏ ÎÏÈÓÈÎÔÂÚÁ·ÛÙËÚȷ΋ ÂÈÎfiÓ· ‹Ù·Ó Ù˘È΋ ÏÔÈÌÒ‰Ô˘˜ ÌÔÓÔ˘Ú‹ÓˆÛ˘. ∆ËÓ 22Ë Ë̤ڷ ·fi ÙËÓ ¤Ó·ÚÍË ÙˆÓ Û˘Ìو̿وÓ, Ô ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·Û ÎËÏȉԂϷÙȉ҉˜ ÂÍ¿ÓıËÌ· Ì ÎÓËÛÌfi οو ¿ÎÚˆÓ, ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· Î·È ˘ÂÚÊÂÚÚÈÙÈÓ·ÈÌ›· (¶›Ó·Î·˜ 2). ∆ËÓ 26Ë Ë̤ڷ ·ÚÔ˘Û›·Û ·Ó·Ó¢ÛÙÈ΋ ‰˘¶·È‰È·ÙÚÈ΋ 2006;69:302-309

Û¯¤ÚÂÈ· ¯ˆÚ›˜ ÎÏÈÓÈÎÔ-·ÎÙÈÓÔÏÔÁÈο ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·, ÂÓÒ ÛÙËÓ ·Ó·ÈÌ›· ÚÔÛÙ¤ıËΠԢ‰ÂÙÂÚÔÂÓ›· (∞∞¶: 400/mm3). §fiÁˆ Ù˘ ÂÈÌÔÓ‹˜ ÙÔ˘ ˘ÚÂÙÔ‡, ¤ÁÈÓ·Ó √¡¶ Î·È MRI ÂÁÎÂÊ¿ÏÔ˘ Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈΤ˜. ∆Ô Ì˘ÂÏfiÁÚ·ÌÌ· Î·È Ë ÔÛÙÂÔÌ˘ÂÏÈ΋ ‚ÈÔ„›· ¤‰ÂÈÍ·Ó ÂÚ˘ıÚÔÊ·ÁÔ΢ÙÙ¿ÚˆÛË. ªÂ ÙË ‰È¿ÁÓˆÛË ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì EBV Ïԛ̈ÍË ÍÂΛÓËÛ ·ÁˆÁ‹ Ì ·Î˘ÎÏÔ‚›ÚË Î·È ÂÓ‰ÔÊϤ‚È· Á-ÛÊ·ÈÚ›ÓË, ÛÙËÓ ÔÔ›· Ô ·ÛıÂÓ‹˜ ‰ÂÓ ·ÓÙ·ÔÎÚ›ıËÎÂ. ∆ËÓ 41Ë Ì¤Ú· Ù˘ ÓfiÛÔ˘ ·ÚÔ˘Û›·Û ‰È·Ù·Ú·¯¤˜ ËÎÙÈÎfiÙËÙ·˜ (·Ú¿Ù·ÛË ÙÔ˘ aPTT), ÔfiÙ ·ÔÊ·Û›ÛÙËÎÂ Ë ¤Ó·ÚÍË ıÂÚ·›·˜ Û‡Ìʈӷ Ì ÙÔ ÚˆÙÔÎfiÏÏÔ HLH 94. √ ·ÛıÂÓ‹˜ ·ÚÔ˘Û›·Û ÛÙ·‰È·Î‹ ˘Ô¯ÒÚËÛË Ù˘ Ë·ÙÔÛÏËÓÔÌÂÁ·Ï›·˜ Î·È ‚ÂÏÙ›ˆÛË ÙˆÓ ·ÈÌ·ÙÔÏÔÁÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ, ηıÒ˜ Î·È ÙÔ˘ ‚ÈÔ¯ËÌÈÎÔ‡ ÚÔÊ›Ï (¶›Ó·Î·˜ 2). √È ·ÓÔÛÔÛÊ·ÈÚ›Ó˜ ÔÚÔ‡ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈΤ˜, ÂÓÒ Ô ¤ÏÂÁ¯Ô˜ ÙˆÓ ÏÂÌÊÔ΢ÙÙ·ÚÈÎÒÓ ÏËı˘ÛÌÒÓ ¤‰ÂÈÍ ·Ó·ÛÙÚÔÊ‹ ÙÔ˘ ÏfiÁÔ˘ CD4+/CD8+ (0,15 ¤ˆ˜ 0,4) ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂÚ·›·˜. √ ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô˜ ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ¤‰ÂÈÍ ÈÛ¯˘Ú‹ ¤ÎÊÚ·ÛË ÙˆÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Î·È ˘„ËÏfi ÔÛÔÛÙfi ·ÓÙÈÁÔÓÔ·ÚÔ˘ÛÈ·ÛÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (CD8+ 78,4%, CD2+/CD86+ 30%, CD1a+ 56,2%, CD40+ 60%). √ ÏËı˘ÛÌfi˜ ÙˆÓ ¡∫-΢ÙÙ¿ÚˆÓ ‹Ù·Ó ÂÏ·Ùو̤ÓÔ˜ (1,8%). ∆· Â›‰· ÙÔ˘ sCD25 Î·È ÙÔ˘ TNFa ÛÙÔÓ ÔÚfi ‹Ù·Ó ·˘ÍË̤ӷ (2190 U/ml Î·È 915 pg/ml, ·ÓÙ›ÛÙÔȯ·), ÂÓÒ ÌÂÙ¿ ÙË ıÂÚ·›· ÂÏ·ÙÙÒıËÎ·Ó (588 U/ml Î·È 37,8 pg/ml, ·ÓÙ›ÛÙÔȯ·).

307

πÔÁÂÓ¤˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ ÛÙ· ·È‰È¿

¶›Ó·Î·˜ 3. ∞Ó·ıˆÚË̤ӷ ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· (3) ∏̤ڷ ÓfiÛÔ˘ ● ●

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√ÈÎÔÁÂÓ‹˜ ÓfiÛÔ˜ / ÁÓˆÛÙ‹ ÁÂÓÂÙÈ΋ ‰È·Ù·Ú·¯‹ ∫ÏÈÓÈο Î·È ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· (¤ÓÙ ·fi Ù· ÔÎÙÒ) ñ ¶˘ÚÂÙfi˜ ñ ™ÏËÓÔÌÂÁ·Ï›· ñ ∫˘ÙÙ·ÚÔÂÓ›· (Â›‰Ú·ÛË Û ≥2 ÛÂÈÚ¤˜ ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜) - ·ÈÌÔÛÊ·ÈÚ›ÓË <9 g/dl (ÚÈÓ ÙȘ 4 ‚‰ÔÌ¿‰Â˜ <10 g/dl) - ·ÈÌÔÂÙ¿ÏÈ· (<100x103/ÌL) - Ô˘‰ÂÙÂÚfiÊÈÏ· (<1,0x103/ÌL) ñ ÀÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›· ηÈ/‹ ˘Ô˚Óˆ‰ÔÁÔÓ·ÈÌ›· (ÙÚÈÁÏ˘ÎÂÚ›‰È· ÓËÛÙ›·˜ ≥264 mg/dL, ÈÓˆ‰ÔÁfiÓÔ <150 mg/dL) ñ ºÂÚÚÈÙ›ÓË ≥500 Ìg/L ñ sCD25 ≥2400 U/ml ñ ªÂȈ̤ÓË ‹ ·Ô‡Û· ¡∫ ‰Ú·ÛÙËÚÈfiÙËÙ· ñ ∞ÈÌÔÊ·ÁÔ΢ÙÙ¿ÚˆÛË ÛÙÔÓ Ì˘ÂÏfi, ÙÔ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô ˘ÁÚfi ‹ ÛÙÔ˘˜ ÏÂÌÊ·‰¤Ó˜

™ËÌ›ˆÛË: ∂ÈϤÔÓ ÛÙÔȯ›· ·ÔÙÂÏÔ‡Ó Û˘ÌÙÒÌ·Ù· ·fi ÙÔ ∫¡™ Ì ̤ÙÚÈ· ÏÂÈÔ΢ÙÙ¿ÚˆÛË Î·È/‹ ·˘ÍË̤ÓÔ Ï‡Έ̷, ·˘ÍË̤Ó˜ ÙÚ·ÓÛ·ÌÈÓ¿Û˜, ¯ÔÏÂÚ˘ıÚ›ÓË Î·È LDH >1000 U/L. ∂›ÁÔ˘Û· ıÂÚ·›· Û ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ ‰È·Ù·Ú·¯‹ ‹Í˘ ÌÔÚ› Ó· ÍÂÎÈÓ‹ÛÂÈ Ì ¤Ó· ÎÚÈÙ‹ÚÈÔ ÏÈÁfiÙÂÚÔ. ¶ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂÚ·›·˜, ‰Â›ÁÌ·Ù· ·›Ì·ÙÔ˜ Ú¤ÂÈ Ó· ÏËÊıÔ‡Ó Î·È Ó· ‰È·ÙËÚËıÔ‡Ó ÁÈ· Ó· ÂȂ‚·Èˆı› ·Ó·‰ÚÔÌÈο Ë ‰È¿ÁÓˆÛË, Ì ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi sCD25 ‹ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ ¡∫.

¢ÂÓ ‰È·ÈÛÙÒıËΠÌÂÙ¿ÏÏ·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ Ù˘ ÂÚÊÔÚ›Ó˘. √ ¤ÏÂÁ¯Ô˜ ÁÈ· ∏LA Û˘Ì‚·ÙfiÙËÙ· ¤‰ÂÈÍ fiÙÈ Â›Ó·È Ù·˘ÙfiÛËÌÔ˜ Ì ÙÔÓ ·‰ÂÏÊfi ÙÔ˘. ∏ ¯ÔÚ‹ÁËÛË ‰ÂÍ·ÌÂı·˙fiÓ˘ Î·È ÂÙÔÔÛ›‰Ë˜ ‰È·ÎfiËΠÙËÓ 39Ë Â‚‰ÔÌ¿‰· ıÂÚ·›·˜, ÂÓÒ Û˘Ó¯›ÛÙËÎÂ Ë Î·ıËÌÂÚÈÓ‹ ¯ÔÚ‹ÁËÛË Î˘ÎÏÔÛÔÚ›Ó˘. ªÂ ÙËÓ ÔÏÔÎÏ‹ÚˆÛË 52 ‚‰ÔÌ¿‰ˆÓ ıÂÚ·›·˜ Î·È ÂÓÒ Ô ·ÛıÂÓ‹˜ ‹Ù·Ó Û Ï‹ÚË ÎÏÈÓÈÎÔÂÚÁ·ÛÙËÚȷ΋ ‡ÊÂÛË Ù˘ ÓfiÛÔ˘, ‰È·ÎfiËΠÙÔ ıÂÚ·¢ÙÈÎfi ÚˆÙfiÎÔÏÏÔ. ∆Ô ·È‰› ·Ú·Ì¤ÓÂÈ ÂχıÂÚÔ ÓfiÛÔ˘ 12 Ì‹Ó˜ ÌÂÙ¿ ÙÔ Ù¤ÏÔ˜ Ù˘ ıÂÚ·›·˜.

™˘˙‹ÙËÛË ∆Ô Û¯ÂÙÈ˙fiÌÂÓÔ Ì EBV ∞º™ Â›Ó·È Ì›· Û¿ÓÈ· Î·È ÂÙÂÚÔÁÂÓ‹˜ ÓfiÛÔ˜ Ô˘ ·ÔÙÂÏ› ÚfiÎÏËÛË ÁÈ· ÙÔÓ ·È‰›·ÙÚÔ-·ÈÌ·ÙÔÏfiÁÔ. ∏ ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ·fi ¿ÏÏ· ÓÔÛ‹Ì·Ù·, fiˆ˜ ÏÔÈÌ҉˘ ÌÔÓÔ˘Ú‹ÓˆÛË (§ª), Û˘ÛÙËÌ·ÙÈΤ˜ ·˘ÙÔ¿ÓÔÛ˜ ‰È·Ù·Ú·¯¤˜ Î·È ·Ï·ÛÙÈ΋ ·Ó·ÈÌ›·, Û˘¯Ó¿ Â›Ó·È ‰‡ÛÎÔÏË Î·È ¯ÚÂÈ¿˙ÂÙ·È ¿ÓÙ· Ó· ·ÔÎÏÂÈÛÙÔ‡Ó Î·ÎÔ‹ıÂȘ ‹ ˘ÔΛÌÂÓ· ÓÔÛ‹Ì·Ù·, fiˆ˜ ¯ÚfiÓÈ· ÂÓÂÚÁfi˜ Ïԛ̈ÍË ·fi EBV, √∞™ Î·È º§À¡ (1). ∏ ‰È¿ÁÓˆÛË ÛÙËÚ›˙ÂÙ·È ÛÙËÓ ‡·ÚÍË ÙˆÓ ‰È·ÁÓˆÛÙÈÎÒÓ ÎÚÈÙËÚ›ˆÓ Ô˘ ¤¯Ô˘Ó ÚfiÛÊ·Ù· ·Ó·ıˆÚËı› (¶›Ó·Î·˜ 3) (3). ™Ùo √∞™ ÌÔÚ› Ó· Û˘ÌÌÂÙ¤¯ÂÈ Î·È ÏÔÈÌ҉˘ ·Ú¿ÁÔÓÙ·˜ (2,4). ∆Ô ·ÚÓËÙÈÎfi ÔÈÎÔÁÂÓÂÈ·Îfi ÈÛÙÔÚÈÎfi, Ë ËÏÈΛ· ÛÙË ‰È¿ÁÓˆÛË Î·È Ë ·Ô˘Û›· Û˘ÁÁ¤ÓÂÈ·˜ ÂÍ ·›Ì·ÙÔ˜ ÌÂٷ͇ ÙˆÓ ÁÔ-

Ó¤ˆÓ ÙˆÓ ·ÛıÂÓÒÓ ·ÔÌ·ÎÚ‡ÓÔ˘Ó - ·ÏÏ¿ ‰ÂÓ ·ÔÎÏÂ›Ô˘Ó - ÙÔ ÂӉ¯fiÌÂÓÔ ‰È¿ÁÓˆÛ˘ √∞™ (1). ™Â ÔÏϤ˜ ÂÚÈÙÒÛÂȘ √∞™ Û˘ÌÌÂÙ¤¯Ô˘Ó ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ÁÔÓȉ›Ô˘ Ù˘ ÂÚÊÔÚ›Ó˘ (3). ∏ ÂÚÊÔÚ›ÓË ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÂÏÂÁ¯fiÌÂÓË ÂÓÂÚÁÔÔ›ËÛË Ù˘ ΢ÙÙ·ÚÈ΋˜ ·ÓÔÛ›·˜ Î·È ÛÙËÓ ÂÈÙ‹ÚËÛË ÙˆÓ ÌÔÏ˘ÛÌ¤ÓˆÓ ·fi ÈÔ‡˜ ΢ÙÙ¿ÚˆÓ ÛÙËÓ ·È‰È΋ ËÏÈΛ· (3). ∏ º§À¡ Â›Ó·È Ì›· ·ÓÔÛÔÏÔÁÈ΋ ‰È·Ù·Ú·¯‹ Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·˘ÍË̤ÓË Â˘·ÈÛıËÛ›· ÛÙÔÓ Èfi EBV, ÎÂÚ·˘ÓÔ‚fiÏÔ §ª, ηÎÔ‹ıË ÏÂÌÊÒÌ·Ù· Î·È ˘ÔÁ·ÌÌ·ÛÊ·ÈÚÈÓ·ÈÌ›· (5). ∏ ÁÂÓÂÙÈ΋ ‚Ï¿‚Ë ÂÓÙÔ›˙ÂÙ·È ÛÙÔ ÁÔÓ›‰ÈÔ SH2D1A Î·È ÌÂÙ·‚È‚¿˙ÂÙ·È ÌÂ Ê˘ÏÔÛ‡Ó‰ÂÙÔ ˘ÔÏÂÈfiÌÂÓÔ ¯·Ú·ÎÙ‹Ú· (5). ∞ÚÎÂÙ¿ Û˘¯Ó¿ ÂÌÊ·Ó›˙ÂÙ·È Ì ÚÒÙË ÂΉ‹ÏˆÛË ÙÔ ∞º™. ∂Âȉ‹ ·Ó·Ê¤ÚÔÓÙ·È Î·È ÛÔÚ·‰ÈΤ˜ ÌÔÚʤ˜ Ù˘ ÓfiÛÔ˘, fiÏ· Ù· ¿ÚÚÂÓ· ·È‰È¿ Ì ∞º™ ı· Ú¤ÂÈ Ó· ÂϤÁ¯ÔÓÙ·È ÁÂÓÂÙÈο ÁÈ· º§À¡, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ ‡·ÚÍË ‹ fi¯È ıÂÙÈÎÔ‡ ÔÈÎÔÁÂÓÂÈ·ÎÔ‡ ÈÛÙÔÚÈÎÔ‡ (5). ∏ ·Ô˘Û›· ˘ÔÁ·ÌÌ·ÛÊ·ÈÚÈÓ·ÈÌ›·˜ Î·È ÛÙÔ˘˜ ‰‡Ô ·ÛıÂÓ›˜ Â›Ó·È ÈÛ¯˘Ú‹ ¤Ó‰ÂÈÍË ·ÔÎÏÂÈÛÌÔ‡ Ù˘ ‰È¿ÁÓˆÛ˘ Ù˘ º§À¡ (2). ∂ÓÙÔ‡ÙÔȘ, Ë ÌÂÚÈ΋ ·ÓÙ·fiÎÚÈÛË ÛÙË ıÂÚ·›· Î·È ÔÈ Â·ÓÂÈÏËÌ̤Ó˜ ˘ÔÙÚÔ¤˜ Ù˘ ÓfiÛÔ˘ ÛÙÔÓ ÚÒÙÔ ·ÛıÂÓ‹ Â›Ó·È Â˘Ú‹Ì·Ù· Ô˘ ÌÔÚ› Ó· ˘ÔÎÚ‡ÙÔ˘Ó ÁÂÓÂÙÈ΋ ·ÓÔÛÔÏÔÁÈ΋ ÚԉȿıÂÛË. ∫·È ÔÈ ‰‡Ô ·ÛıÂÓ›˜ ‰ÂÓ ÏËÚÔ‡Û·Ó ÙÔ Û‡ÓÔÏÔ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ÈÔÁÂÓÔ‡˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ (π∞™) ÛÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÓfiÛÔ˘. √È Î˘ÙÙ·ÚÔÂӛ˜ ÌÔÚ› Ó· ¶·È‰È·ÙÚÈ΋ 2006;69:302-309

308

∂. ¢ËÏ·Ó¿˜ Î·È Û˘Ó.

ÂΉËÏÒÓÔÓÙ·È ÓˆÚ›˜ ηٿ ÙËÓ ÂͤÏÈÍË Ù˘ ÓfiÛÔ˘, ÂÂȉ‹ fï˜ ÌÔÚ› Ó· ÌËÓ Â›Ó·È ÛÔ‚·Ú¤˜, ıˆÚÂ›Ù·È ÂÚÈÛÛfiÙÂÚÔ ‰È·ÁÓˆÛÙÈ΋ Ë ÚÔԉ¢ÙÈ΋ ÂÁηٿÛÙ·Û‹ ÙÔ˘˜, ·Ú¿ Ô ·fiÏ˘ÙÔ˜ ·ÚÈıÌfi˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ·›Ì·ÙÔ˜ (6). ™ÙÔÓ ÚÒÙÔ ·ÛıÂÓ‹, ÔÈ Â·ÓÂÈÏËÌ̤Ó˜ ÔÛÙÂÔÌ˘ÂÏÈΤ˜ ‚ÈÔ„›Â˜ ‰ÂÓ ‹Ù·Ó ‰È·ÁÓˆÛÙÈΤ˜ Î·È Ë ‰È¿ÁÓˆÛË Ù¤ıËΠ̠ÛÏËÓÂÎÙÔÌ‹ Î·È ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË ÙÔ˘ ÛÏ‹Ó·. ™ÙË ‚È‚ÏÈÔÁÚ·Ê›· ·Ó·Ê¤ÚÂÙ·È fiÙÈ ÌfiÓÔ ÛÙÔ 1/3 ÙˆÓ ÂÚÈÙÒÛÂˆÓ ·ÓȯÓ‡ÂÙ·È ·ÈÌÔÊ·ÁÔ΢ÙÙ¿ÚˆÛË ÛÙÔ ·Ú¯ÈÎfi ‰Â›ÁÌ· Ì˘ÂÏÔ‡ (3). ™ÙÔÓ ÚÒÙÔ ·ÛıÂÓ‹, Ë ˘Ô˚Óˆ‰ÔÁÔÓ·ÈÌ›· Î·È Ë ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·, Ô˘ ·ÔÙÂÏÔ‡Ó Ù· Û˘ÓËı¤ÛÙÂÚ· ·fiÓÙ· ÎÚÈÙ‹ÚÈ· (1), ÙÂÎÌËÚÈÒıËÎ·Ó ·ÚÎÂÙ¤˜ Ë̤Ú˜ ÌÂÙ¿ ÙËÓ ÂÌÊ¿ÓÈÛË ÙˆÓ ÚÒÙˆÓ Û˘Ìو̿وÓ. ∂Í¿ÏÏÔ˘, ÛÙÔÓ ‰Â‡ÙÂÚÔ ·ÛıÂÓ‹ ·ÚÔ˘ÛÈ¿ÛÙËΠÌfiÓÔ ˘ÂÚÙÚÈÁÏ˘ÎÂÚȉ·ÈÌ›·. ∏ ÊÂÚÚÈÙ›ÓË Î·È Ë LDH, Ô˘ ·ÔÙÂÏÔ‡Ó ‰Â›ÎÙ˜ Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘ Î·È ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ˘ÔÙÚÔ‹˜, ‹Ù·Ó ÛÙ·ıÂÚ¿ ·˘ÍË̤Ó˜ ηٿ ÙȘ ˘ÔÙÚÔ¤˜ Ù˘ ÓfiÛÔ˘ ÙÔ˘ ÚÒÙÔ˘ ·ÛıÂÓÔ‡˜ (1,2). ™ÙÔ˘˜ ‰‡Ô ·ÛıÂÓ›˜, Ë ÔÍ›· Ïԛ̈ÍË ·fi EBV ÙÂÎÌËÚÈÒıËΠÌÂ Û˘Ó‰˘·ÛÌfi ÔÚÔÏÔÁÈÎÔ‡ ¤ÏÂÁ¯Ô˘ Î·È PCR ÛÙ· ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜. ∏ ÔÚÔÏÔÁÈ΋ ·Ó›¯Ó¢ÛË ÙÔ˘ ÈÔ‡ ‰ÂÓ Â›Ó·È ¿ÓÙ· Â·Ú΋˜ Î·È Ë ÌÔÚȷ΋ ·Ó¿Ï˘ÛË Ì PCR ıˆÚÂ›Ù·È ·Ó·Áη›· (2). ∆Ô ÂÂÈÛfi‰ÈÔ Û·ÛÌÒÓ Î·È Ô Ï‹ı·ÚÁÔ˜ Ô˘ ·ÚÔ˘Û›·ÛÂ Ô ÚÒÙÔ˜ ·ÛıÂÓ‹˜, ·ÔÙÂÏÔ‡Ó ÂӉ›ÍÂȘ ÚÔÛ‚ÔÏ‹˜ ÙÔ˘ ∫¡™, ·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ù· Â˘Ú‹Ì·Ù· ·fi ÙËÓ √¡¶ Î·È ÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. ∏ ÓfiÛÔ˜ ÙÔ˘ ∫¡™ Â›Ó·È Û˘¯Ó‹ (7) Î·È ÌÔÚ› Ó· ÂΉËψı› Ì ‰È¤ÁÂÚÛË, ·˘¯ÂÓÈ΋ ‰˘Ûη̄›·, ·Ù·Í›·, ·Ú¿Ï˘ÛË ÂÁÎÂÊ·ÏÈÎÒÓ Û˘˙˘ÁÈÒÓ, ÂÓ‰ÔÎÚ¿ÓÈ· ˘¤ÚÙ·ÛË Î·È ÎÒÌ·. ¢ÂÓ ·ÔÙÂÏ› ‰˘ÛÌÂÓ‹ ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ· Û ÌÂÁ¿Ï˜ ÛÂÈÚ¤˜ ·ÛıÂÓÒÓ (8), ÂÊfiÛÔÓ ÂÈÙ¢¯ı› ‡ÊÂÛË Î·È Á›ÓÂÈ ·ÏÏÔÁÂÓ‹˜ ªª√. µ·ÛÈÎfi ÚfiÏÔ ÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙÔ˘ ∞º™ ·›˙Ô˘Ó Ù· ΢ÙÙ·ÚÔÙÔÍÈο ∆- Î·È ¡∫-ÏÂÌÊÔ·ÙÙ·Ú·. º˘ÛÈÔÏÔÁÈο, Ù· ·ÙÙ·Ú· ·˘Ù¿ ÚÔηÏÔ‡Ó ÙËÓ ·fiÙˆÛË ¿ÏÏˆÓ ‰˘ÓËÙÈο ÂÈΛӉ˘ÓˆÓ ·ÓÔÛÔÏÔÁÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (9). ∏ ¡∫ ‰Ú·ÛÙËÚÈfiÙËÙ·, Ë ÔÔ›· ıˆÚÂ›Ù·È ‰Â›ÎÙ˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘, Â›Ó·È ÛÙ·ıÂÚ¿ ·Ô‡Û· ‹ ‰Ú·Ì·ÙÈο ÂÏ·Ùو̤ÓË ÛÙÔ √∞™. ∞ÓÙ›ıÂÙ·, ÛÙÔ π∞™ ÌÔÚ› Ó· Â›Ó·È ÌÂȈ̤ÓË Î·Ù¿ ÙËÓ ÔÍ›· Ê¿ÛË Ù˘ ÓfiÛÔ˘ ÌÂ Û˘ÓÔ‰fi ·Ô˘Û›· ÙˆÓ Î˘ÎÏÔÊÔÚÔ‡ÓÙˆÓ ¡∫-΢ÙÙ¿ÚˆÓ Î·È Û˘Ó‹ıˆ˜ Â·Ó¤Ú¯ÂÙ·È ÛÙ· Ê˘ÛÈÔÏÔÁÈο Â›‰· ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË ıÂÚ·›·˜ (3,9). ™ÙÔÓ ÚÒÙÔ ·Ûı¶·È‰È·ÙÚÈ΋ 2006;69:302-309

Ó‹, Ë ¡∫ ‰Ú·ÛÙËÚÈfiÙËÙ· ·Ú¤ÌÂÈÓ ÂÏ·Ùو̤ÓË, fï˜ ÙÔ Â‡ÚËÌ· ·˘Ùfi ‰ÂÓ ÙÂÎÌËÚÈÒÓÂÈ √∞™. ∏ ·Ó·ÛÙÚÔÊ‹ ÙÔ˘ ÏfiÁÔ˘ CD4+/CD8+ ÛÙÔ˘˜ ‰‡Ô ·ÛıÂÓ›˜ ·ÓÙ·Ó·ÎÏ¿ ÙËÓ ·‡ÍËÛË ÙˆÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ CD8+ ¤Ó·ÓÙÈ ÙˆÓ ‚ÔËıËÙÈÎÒÓ CD4+ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ∏ ÌË ÂÏÂÁ¯fiÌÂÓË ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ∆-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Î·È Ë Â·ÎfiÏÔ˘ıË ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ Ô‰ËÁ› Û ˘ÂÚ·Ú·ÁˆÁ‹ ΢ÙÙ·ÚÔÎÈÓÒÓ (2). ∆· Â›‰· ÙˆÓ πL-8, TNF-· Î·È sCD-25 ÛÙÔÓ ÔÚfi, Ô˘ ·ÓÙ·Ó·ÎÏÔ‡Ó ÙË ‰Ú·ÛÙËÚÈfiÙËÙ· ÙˆÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ Î˘ÙÙ¿ÚˆÓ, ¤¯Ô˘Ó ‰È·ÁÓˆÛÙÈ΋ Î·È ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›· (2,3). ∆· Â›‰· ÙÔ˘ sCD25 ÛÙÔÓ ÔÚfi ÙˆÓ ‰‡Ô ·ÛıÂÓÒÓ ‹Ù·Ó ·˘ÍË̤ӷ, ·ÏÏ¿ Ôχ ¯·ÌËÏfiÙÂÚ· ·fi 10.000 U/ml, ÙÈÌ‹ Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÈ ÙÔ EBV-∞º™ (10). ªÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ¯ËÌÂÈÔıÂÚ·›·˜ ÛÙÔÓ ÚÒÙÔ ·ÛıÂÓ‹, Ù· Â›‰· ÙÔ˘ sCD25 ·ÚÔ˘Û›·Û·Ó Ì›ˆÛË, ·ÏÏ¿ ·Ú¤ÌÂÈÓ·Ó ·ıÔÏÔÁÈο. ∂›Û˘, ·˘ÍË̤ӷ ‹Ù·Ó Ù· Â›‰· ÙˆÓ IL-8 Î·È TNF-a ÛÙÔÓ ÚÒÙÔ ·ÛıÂÓ‹ Î·È TNF-a ÛÙÔÓ ‰Â‡ÙÂÚÔ, Â˘Ú‹Ì·Ù· Û˘Ì‚·Ù¿ Ì π∞™ (2). ¶·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ù· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ‰ÂÓ Â›Ó·È ¿ÌÂÛ· ‰È·ı¤ÛÈÌ·, ¤¯Ô˘Ó ·Ó·‰ÚÔÌÈ΋ ·Í›· ÛÙËÓ ·Ó·ÁÓÒÚÈÛË Ù˘ ˘ÔΛÌÂÓ˘ ÓfiÛÔ˘ Î·È ÌÔÚ› Ó· Û˘Ì‚¿ÏÏÔ˘Ó ÌÂÏÏÔÓÙÈο ÛÙÔÓ Î·ıÔÚÈÛÌfi ıÂÚ·¢ÙÈÎÒÓ ÛÙÚ·ÙËÁÈÎÒÓ. ¶·Ú¿ ÙËÓ ‡·ÚÍË ·˘ÛÙËÚÒÓ ‰È·ÁÓˆÛÙÈÎÒÓ ÎÚÈÙËÚ›ˆÓ, Ë ÓfiÛÔ˜ ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÂÁ¿ÏË ÎÏÈÓÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ·, ·fi ‹Ș ·˘ÙÔÂÚÈÔÚÈ˙fiÌÂÓ˜ ÌÔÚʤ˜ ̤¯ÚÈ ·ÓıÂÎÙÈΤ˜ ı·Ó·ÙËÊfiÚ˜ ÂÚÈÙÒÛÂȘ. ∏ ıÓËÙfiÙËÙ· ·fi EBV-∞º™ Â›Ó·È ÛËÌ·ÓÙÈ΋ (ÔÛÔÛÙfi 20-40%) Î·È Â›Ó·È Â›Ù ÚÒÈÌË ÏfiÁˆ ¢ηÈÚÈ·ÎÒÓ ÏÔÈÌÒÍÂˆÓ Î·È ¢∂¶, ›Ù fi„ÈÌË Î˘Ú›ˆ˜ ÏfiÁˆ ·ÓıÂÎÙÈ΋˜ ÓfiÛÔ˘ Î·È ÙÔÍÈÎfiÙËÙ·˜ Ù˘ ıÂÚ·›·˜ (11). ∏ ıÂÚ·›· ÙÔ˘ EBV-∞º™ ·Ú¯Èο ÂÚÈÏ·Ì‚¿ÓÂÈ ˘ÔÛÙËÚÈÎÙÈ΋ ·ÁˆÁ‹ Î·È Û ‹Ș ÂÚÈÙÒÛÂȘ ¯ÔÚ‹ÁËÛË ÂÓ‰ÔÊϤ‚È·˜ Á-ÛÊ·ÈÚ›Ó˘ Î·È ·Î˘ÎÏÔ‚›Ú˘, Ì ·ÌÊ›‚ÔÏË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· (2,6). ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ˘ÔÛÙËÚ›˙ÂÙ·È Ë ¤ÁηÈÚË ¯ÔÚ‹ÁËÛË ıÂÚ·›·˜ Ì ‚¿ÛË ÙÔ ÚˆÙfiÎÔÏÏÔ HLH-94 (3). ∆Ô ÚˆÙfiÎÔÏÏÔ ÂÚÈÏ·Ì‚¿ÓÂÈ Û˘Ó‰˘·Ṳ̂ÓË ¯ÔÚ‹ÁËÛË ÂÙÔÔÛ›‰Ë˜, ‰ÂÍ·ÌÂı·˙fiÓ˘ Î·È ÚÔÛı‹ÎË Î˘ÎÏÔÛÔÚ›Ó˘ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ê¿Û˘ ‰È·Ù‹ÚËÛ˘ Ù˘ ‡ÊÂÛ˘ (∂ÈÎfiÓ· 1). ªÂÙ¿ ÙËÓ ÂÓÙ·ÙÈ΋ ¯ËÌÂÈÔıÂÚ·›· ÂÊfi‰Ô˘, ‰È¿ÚÎÂÈ·˜ 8 ‚‰ÔÌ¿‰ˆÓ, ·ÔÊ·Û›˙ÂÙ·È Ë ÂÚ·ÈÙ¤Úˆ Û˘Ó¤¯ÈÛË ‹ ‰È·ÎÔ‹ Ù˘ ıÂÚ·›·˜ ·Ó¿ÏÔÁ· Ì ÙËÓ ·ÓÙ·fiÎÚÈÛË (4). ∂ÓÙÔ‡ÙÔȘ, ·Ó·Ê¤ÚÂÙ·È ¤ˆ˜ Î·È 30% ˘ÔÙÚÔ‹ Ù˘ ÓfiÛÔ˘ Û ·ÛıÂÓ›˜ Ì Ï‹ÚË

309

πÔÁÂÓ¤˜ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ ÛÙ· ·È‰È¿

·ÓÙ·fiÎÚÈÛË Ô˘ ‰È¤ÎÔ„·Ó ÙÔ HLH-94 ÛÙȘ 8 ‚‰ÔÌ¿‰Â˜ ıÂÚ·›·˜ (12). ™Â ÂÚÈÙÒÛÂȘ ·ÓıÂÎÙÈΤ˜ ÛÙÔ ÚˆÙfiÎÔÏÏÔ HLH-94 ÂÊ·ÚÌfi˙ÔÓÙ·È ‰È¿ÊÔÚ· ¯ËÌÂÈÔıÂÚ·¢ÙÈο Û¯‹Ì·Ù· ÏÂÌʈ̿وÓ, ˆ˜ ıÂÚ·›· ‰È¿ÛˆÛ˘ ̤¯ÚÈ Ó· ÔÏÔÎÏËÚˆı› Ë ·Ó·˙‹ÙËÛË Û˘Ì‚·ÙÔ‡ ‰fiÙË ÁÈ· ·ÏÏÔÁÂÓ‹ ªª√, Ô˘ ·ÔÙÂÏ› Î·È ÙË ÚÈ˙È΋ ıÂÚ·›· (2). ∞fiÏ˘Ù˜ ÂӉ›ÍÂȘ ÁÈ· ·ÏÏÔÁÂÓ‹ ªª√ ıˆÚÔ‡ÓÙ·È Ë º§À¡, ÙÔ √∞™, ÔÈ ·ÓıÂÎÙÈΤ˜ ÌÔÚʤ˜ EBV-∞º™ Ì ˘„ËÏÔ‡˜ Ù›ÙÏÔ˘˜ ·ÓÙÈۈ̿وÓ, ˘„ËÏfi ·ÚÈıÌfi ΢ÎÏÔÊÔÚÔ‡ÓÙˆÓ ¡∫ (>40% ÛÙÔ ÂÚÈÊÂÚÈÎfi ·›Ì·), Ë ·Ú·ÌÔÓ‹ ˘„ËÏÔ‡ ÈÈÎÔ‡ ÊÔÚÙ›Ô˘ Î·È Ë ÊÙˆ¯‹ ·ÓÙ·fiÎÚÈÛË ÛÙË ¯ËÌÂÈÔıÂÚ·›· Ì ÂÙÔÔÛ›‰Ë (2). ™Â Ì›· ÚfiÛÊ·ÙË ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË 40 ·ÛıÂÓÒÓ, Ë ÙÚÈÂÙ‹˜ ÂÈ‚›ˆÛË ÌÂÙ¿ ·ÏÏÔÁÂÓ‹ ªª√ ‹Ù·Ó 62% (4). ™ÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ ÚÒÙÔ˘ ·ÛıÂÓÔ‡˜ ÌÂÛÔÏ¿‚ËÛ ÌÂÁ¿ÏÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ̤¯ÚÈ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ‰ÂÓ ˘‹Ú¯Â ‰È·ı¤ÛÈÌÔ˜ Û˘Ì‚·Ùfi˜ ‰fiÙ˘. ∏ ÌÂÁ¿ÏË Î·ı˘ÛÙ¤ÚËÛË Î·È Ë ·ıÚÔÈÛÙÈ΋ ÙÔÍÈÎfiÙËÙ· ·fi ÙË ¯ÔÚËÁÔ‡ÌÂÓË ¯ËÌÂÈÔıÂÚ·›·, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ÌÂÚÈ΋ Û˘Ì‚·ÙfiÙËÙ· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Û˘ÓÂÙ¤ÏÂÛ·Ó ÛÙÔ ÌÔÈÚ·›Ô ·ÔÙ¤ÏÂÛÌ·. ∞ÓÙ›ıÂÙ·, Ë ¤ÁηÈÚË ¤Ó·ÚÍË ıÂÚ·›·˜ ÛÙÔÓ ‰Â‡ÙÂÚÔ ·ÛıÂÓ‹, ηıÒ˜ ˘‹Ú¯Â Î·È ÌÂÁ·Ï‡ÙÂÚÔ˜ ‚·ıÌfi˜ ÎÏÈÓÈ΋˜ ˘Ô„›·˜, Û˘ÓÂÙ¤ÏÂÛ ÛÙËÓ ÂÈÙ˘¯‹ ¤Î‚·ÛË. ™˘ÌÂÚ·ÛÌ·ÙÈο, ÙÔ ·ÈÌÔÊ·ÁÔ΢ÙÙ·ÚÈÎfi Û‡Ó‰ÚÔÌÔ Â›Ó·È ÎÏÈÓÈο Î·È ÁÂÓÂÙÈο ÂÙÂÚÔÁÂÓ‹˜ ÓfiÛÔ˜, ‰˘ÓËÙÈο ı·Ó·ÙËÊfiÚ·, Ô˘ Û˘¯Ó¿ Û˘Ó‰¤ÂÙ·È Ì Ïԛ̈ÍË ·fi ÙÔÓ EBV ηٿ ÙËÓ ·È‰È΋ ËÏÈΛ·. √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ΢ÙÙ·ÚÔÎÈÓÒÓ, ·ÓÔÛÔÊ·ÈÓÔÙ‡Ô˘, ‚ÈÔ¯ËÌÈÎÒÓ ‰ÂÈÎÙÒÓ, ¡∫ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Î·È ÁÔÓȉȷ΋˜ ·Ó¿Ï˘Û˘ ¤¯ÂÈ ÚÔÁÓˆÛÙÈ΋ ·Í›· Î·È ÌÔÚ› Ó· ηıÔÚ›ÛÂÈ ÙË ıÂÚ·›·. ∏ ¤ÁηÈÚË ¤Ó·ÚÍË ıÂÚ·›·˜ ‚ÂÏÙÈÒÓÂÈ ÛËÌ·ÓÙÈο ÙËÓ ÚfiÁÓˆÛË, ÂÓÒ Û ÛÔ‚·Ú¤˜ Î·È ·ÓıÂÎÙÈΤ˜ ÂÚÈÙÒÛÂȘ ‰ÈÂÓÂÚÁÂ›Ù·È ·ÏÏÔÁÂÓ‹˜ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·Ú¯¤ÁÔÓˆÓ ·ÈÌÔÔÈËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ.

∂˘¯·ÚÈÛٛ˜ ∂˘¯·ÚÈÛÙԇ̠ıÂÚÌ¿ ÙËÓ Î·ıËÁ‹ÙÚÈ· G. JankaSchaub ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ÙÔ˘ ∞Ì‚Ô‡ÚÁÔ˘ Ù˘ °ÂÚÌ·Ó›·˜, Ô˘ ·Ó¤Ï·‚ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË

Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ ÙÔ˘ ÚÒÙÔ˘ ·ÛıÂÓÔ‡˜, ηıÒ˜ Î·È ÙË Dr. E. Marion Schneider ÛÙÔ ∆Ì‹Ì· Ù˘ ¶ÂÈÚ·Ì·ÙÈ΋˜ ∞Ó·ÈÛıËÛÈÔÏÔÁ›·˜ ÛÙÔ ¶·ÓÂÈÛÙ‹ÌÈÔ Ù˘ Ulm ÛÙË °ÂÚÌ·Ó›·, Ô˘ Ú·ÁÌ·ÙÔÔ›ËÛ ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·È ÙÔÓ ÁÔÓȉȷÎfi ¤ÏÂÁ¯Ô.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Imashuku S. Differential diagnosis of hemophagocytic syndrome: underlying disorders and selection of the most effective treatment. Int J Hematol 1997; 66:135-151.

2. Imashuku S. Clinical features and treatment strategies of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Crit Rev Oncol Hematol 2002;44:259-272.

3. Janka GE, Schneider EM. Modern management of children with haemophagocytic lymphohistiocytosis. Br J Haematol 2004;124:4-14.

4. Henter JI, Samuelsson-Horne A, Arico M, Egeler RM, Elinder G, Filipovich A∏ et al. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002;100:2367-2373.

5. Arico M, Imashuku S, Clementi R, Hibi S, Teramura T, Danesino C et al. Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the Xlinked lymphoproliferative disease gene. Blood 2001;97:1131-1133.

6. Tsuda H. Hemophagocytic syndrome (HPS) in children and adults. Int J Hematol 1997;65:215-226.

7. Haddad E, Sulis ML, Jabado N, Blanche S, Fischer A, Tardieu M. Frequency and severity of central nervous system lesions in hemophagocytic lymphohistiocytosis. Blood 1997;89:794-800.

8. Baker KS, DeLaat CA, Steinbuch M, Gross TG, Shapiro RS, Loechelt B et al. Successful correction of hemophagocytic lymphohistiocytosis with related or unrelated bone marrow transplantation. Blood 1997;89:3857-3863.

9. Filipovich AH. Hemophagocytic lymphohistiocytosis.

Immunol Allergy Clin North Am 2002;22:281-300.

10. Imashuku S, Hibi S, Sako M, Ishida Y, Mugishima H, Chen J et al. Soluble interleukin-2 receptor: a useful prognostic factor for patients with hemophagocytic lymphohistiocytosis. Blood 1995;86:4706-4707.

11. Imashuku S, Teramura T, Tauchi H, Ishida Y, Otoh Y, Sawada M et al. Longitudinal follow-up of patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Haematologica 2004;89:183-188.

12. Imashuku S. Advances in the management of hemophagocytic lymphohistiocytosis. Int J Hematol 2000; 72:1-11.

¶·È‰È·ÙÚÈ΋ 2006;69:302-309

310

∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏

CASE REPORT

√Í›· ·ÁÎÚ·ٛÙȉ· Û ·È‰› Ì Ïԛ̈ÍË ·fi Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ B’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, µÂÓÈ˙¤ÏÂÈÔ °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ AÏÏËÏÔÁÚ·Ê›·: ∞. ∆ÛÈÏÈÌÈÁοÎË ∏ÚÔ‰fiÙÔ˘ 214, T.K. 716 01 ¡¤· ∞ÏÈηÚÓ·ÛÛfi˜, ∏Ú¿ÎÏÂÈÔ, ∫Ú‹Ù˘ E-mail: tsilimig@in.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 15-02-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 14-12-2005

¶. ¡ÂÔÓ¿ÎË, ™. ª¿Ú·Î·, ™. ™ÙÂÊ·Ó¿ÎË, ∞. ∆ÛÈÏÈÌÈÁοÎË

¶ÂÚ›ÏË„Ë: ¶ÂÚÈÁÚ¿ÊÂÙ·È ÂÚ›ÙˆÛË ·ÁÔÚÈÔ‡ ËÏÈΛ·˜ 14 ÂÙÒÓ Ô˘ ÓÔÛËχÙËΠÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÁÈ· ¿Ù˘Ë Ó¢ÌÔÓ›·. √ ·ÛıÂÓ‹˜, ÙËÓ ¤ÌÙË Ë̤ڷ Ù˘ ÓÔÛËÏ›·˜ ÙÔ˘, ÂÌÊ¿ÓÈÛ ÎÏÈÓÈο Î·È ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜. ∞fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô, ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ ·ԉ›¯ÙËΠˆ˜ o ·ÈÙÈÔÏÔÁÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Ù˘ Ïԛ̈͢. ∏ ÔÍ›· ·ÁÎÚ·ٛÙȉ· ·ÔÙÂÏ› Û¿ÓÈ· Â͈Ó¢ÌÔÓÈ΋ ÂΉ‹ÏˆÛË Ù˘ Ïԛ̈͢ ·fi Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜. ªfiÓÔ Ï›Á˜ ÙÂÎÌËÚȈ̤Ó˜ ÂÚÈÙÒÛÂȘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ηÈ, ·’ fiÛÔ ÁÓˆÚ›˙Ô˘ÌÂ, Ë ·ÚÔ‡Û· Â›Ó·È Ë ÚÒÙË ÛÙËÓ ÂÏÏËÓÈ΋ ‚È‚ÏÈÔÁÚ·Ê›·. §¤ÍÂȘ ÎÏÂȉȿ: ÕÙ˘Ë Ó¢ÌÔÓ›·, ÔÍ›· ·ÁÎÚ·ٛÙȉ·, Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜.

Acute pancreatitis in a child with pneumonia due to Mycoplasma pneumoniae 2nd Paediatric Clinic, Venizeleio General Hospital, Herakleion, Crete Correspondence: A. Tsilimigaki 214, Herodotou Str. 716 01, Herakleion, Crete, Greece E-mail: tsilimig@in.gr Date of submission: 15-02-2005 Date of approval: 14-12-2005

P. Neonaki, S. Maraka, S. Stefanaki, ∞. Tsilimigaki

Abstract: The case is reported of a 14 year-old boy who was admitted with atypical pneumonia. He developed the symptoms, signs and laboratory findings of acute pancreatitis on the fifth day of his hospitalization. Laboratory examination demonstrated positive Mycoplasma pneumoniae serology.

Acute pancreatitis is a very unusual non-respiratory manifestation of Mycoplasma pneumoniae. Only a few cases of acute pancreatitis associated with Mycoplasma pneumoniae have been reported in the international literature and this is the first to be described in the Greek literature.

Key words: Atypical pneumonia, acute pancreatitis, Mycoplasma pneumoniae.

∂ÈÛ·ÁˆÁ‹ ∏ Ïԛ̈ÍË ·fi ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ ·ÊÔÚ¿ Û˘Ó‹ıˆ˜ ·È‰È¿ Û¯ÔÏÈ΋˜ ËÏÈΛ·˜ Î·È Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ. ∏ Ó¢ÌÔÓ›· ·ÔÙÂÏ› ÙËÓ ÈÔ Û˘¯Ó‹ ÂΉ‹ÏˆÛË Ù˘ Ïԛ̈͢ Î·È Î·Ï‡ÙÂÈ Ì¤¯ÚÈ Î·È ÙÔ 20% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ó¢ÌÔÓ›·˜ Ù˘ ÎÔÈÓfiÙËÙ·˜ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi (1,2). ∏ ÎÏÈÓÈ΋ ÔÚ›· Ù˘ Ó¢ÌÔÓ›·˜ Â›Ó·È Û˘Ó‹ıˆ˜ ‹È·, ·ÏÏ¿ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÛÔ‚·Ú¤˜ ÂÈÏÔΤ˜ Ô˘ ·˘Í¿ÓÔ˘Ó ÙË ÓÔÛËÚfiÙËÙ· Î·È ÙË ıÓËÙfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ (1). √È Â͈Ó¢ÌÔÓÈΤ˜ ÂΉËÏÒÛÂȘ ·ÊÔÚÔ‡Ó fiÏ· Ù· Û˘ÛÙ‹Ì·Ù· Î·È ÂÌÊ·Ó›˙ÔÓÙ·È 1-21 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ ·Ó·Ó¢ÛÙÈ΋ ÓfiÛÔ, ·Ó Â›Ó·È ‰˘Ó·ÙfiÓ Ë ÚˆÙÔ·ı‹˜ Ïԛ̈ÍË ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ Ó· ÌËÓ Â›Ó·È ÎÏÈÓÈο ÂÌÊ·Ó‹˜. ™Â ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË, Ë ¤ÁηÈÚË ·ÈÙÈÔÏÔÁÈ΋ ‰È¿ÁÓˆÛË ÙˆÓ Â͈Ó¢ÌÔÓÈÎÒÓ ÂΉËÏÒÛÂˆÓ Â›Ó·È È‰È·›ÙÂÚ· ¶·È‰È·ÙÚÈ΋ 2006;69:310-312

‰‡ÛÎÔÏË Î·È ÂÈÙ˘Á¯¿ÓÂÙ·È ÌfiÓÔ Ì ÔÚÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô. ™ÙȘ ÂΉËÏÒÛÂȘ ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi Û‡ÛÙËÌ· ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ¤ÌÂÙÔÈ, ‰È¿ÚÚÔȘ, ÎÔÈÏȷο ¿ÏÁË, ÂÓÒ Û¿ÓÈ· ÌÔÚ› Ó· ÂÌÊ·ÓÈÛÙ› Ë·ÙÈ΋ ‹ ·ÁÎÚ·ÙÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ‹ ·ÈÌÔÚÚ·Á›· ·fi ÙÔ ÂÙÈÎfi (3,4). ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÂÚ›ÙˆÛË ·ÁÔÚÈÔ‡ 14 ÂÙÒÓ Ì ÂÈÎfiÓ· ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ ÛÙË ‰È·‰ÚÔÌ‹ Ïԛ̈͢ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡, Ô˘ ·ԉ›¯ÙËΠÔÚÔÏÔÁÈο, fiÙÈ ÔÊÂÈÏfiÙ·Ó ÛÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌoÓ›·˜.

¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ∞ÁfiÚÈ ËÏÈΛ·˜ 14 ÂÙÒÓ ÂÈÛ‹¯ıË ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ Ì ˘ÚÂÙfi ¤ˆ˜ 39ÔC ·fi ÂÓıË̤ÚÔ˘, ‚‹¯· Î·È ÎÔÈÏÈ·Îfi ¿ÏÁÔ˜ ·fi ‰ÈË̤ÚÔ˘. ∆Ô ·ÙÔÌÈÎfi Î·È ÙÔ ÔÈÎÔÁÂÓÂÈ·Îfi ·Ó·ÌÓËÛÙÈÎfi ·Ó·Ê¤ÚÔÓÙ·È

311

√Í›· ·ÁÎÚ·ٛÙȉ· Û Ïԛ̈ÍË ·fi Ì˘ÎfiÏ·ÛÌ·

ÂχıÂÚ·. √ ·ÛıÂÓ‹˜ ‹Ù·Ó Û ηϋ ÁÂÓÈ΋ ηٿÛÙ·ÛË Î·È ·fi ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË ÙÔ˘ ıÒڷη ‰È·ÈÛÙÒıËÎ·Ó ˘ÁÚÔ› ÚfiÁ¯ÔÈ ÂÓÙÔÈṲ̂ÓÔÈ ÛÙË ‚¿ÛË ·ÚÈÛÙÂÚ¿ Î·È ‹È·, ‰È¿¯˘ÙË Â˘·ÈÛıËÛ›· ÛÙËÓ „ËÏ¿ÊËÛË Ù˘ ÎÔÈÏÈ¿˜. ∞fi Ù· ˘fiÏÔÈ· Û˘ÛÙ‹Ì·Ù· ‰ÂÓ ÚԤ΢„·Ó ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍÂ: WBC: 9580/mmÑ (¶ 59%, § 31%, ª 10%), Hb 13,0 gr/dl, Hct 38,5%, PLT 456.000/mmÑ, ∆∫∂ 73 mm/1Ë ÒÚ· Î·È CRP 4,96 mg/dl, ÁÏ˘Îfi˙Ë ÔÚÔ‡ 108 mg/dl. ∏ Ë·ÙÈ΋ Î·È Ë ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈΤ˜, Ë ¿ÌÂÛË Coombs ıÂÙÈ΋ (+++) Î·È ÔÈ „˘¯ÚÔÛ˘ÁÎÔÏÏËÙ›Ó˜ 1/250 (ıÂÙÈΤ˜). ∏ ·ÎÙÈÓÔÁÚ·Ê›· ıÒÚ·ÎÔ˜ ·ÔÎ¿Ï˘„ ‡ÎÓˆÛË ÛÙË ‚¿ÛË ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ Ó‡ÌÔÓ·. √ ·ÛıÂÓ‹˜ ÂÙ¤ıË Û ·ÁˆÁ‹ Ì ÎÏ·Ú˘ıÚÔÌ˘Î›ÓË ·fi ÙÔ ÛÙfiÌ·. ∆Ô Ù¤Ù·ÚÙÔ 24ˆÚÔ Ù˘ ÓÔÛËÏ›·˜ ÙÔ˘, ÙÔ ·È‰› ÂÌÊ¿ÓÈÛ ¤ÓÙÔÓË ÂÈÁ·ÛÙÚ·ÏÁ›·, Â̤ÙÔ˘˜ Î·È ·ÓÔÚÂÍ›·, Ì ¢·ÈÛıËÛ›· ÛÙËÓ „ËÏ¿ÊËÛË ÛÙÔ ÂÈÁ¿ÛÙÚÈÔ Î·È ÂÚÈÔÌÊ·ÏÈο. √ Ó¤Ô˜ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ¤‰ÂÈÍÂ: WBC 5.160/mmÑ (¶ 58%, § 32%, ª 10%), Hb 12,8 gr/dl, Hct 38,2%, PLT 393.000/mmÑ, TKE 55mm/1Ë ÒÚ· Î·È CRP 2,46 mg/dl, ÁÏ˘Îfi˙Ë ÔÚÔ‡ 97 mg/dl. ∏ Ë·ÙÈ΋ Î·È Ë ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈΤ˜, ·Ì˘Ï¿ÛË ÔÚÔ‡ 1287 U/L (º.∆.<180 U/L). √ ·ÈÌÔÚÚ·ÁÈÎfi˜ Î·È o ÏÈȉ·ÈÌÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎÔ›. ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÎÔÈÏ›·˜ ¤‰ÂÈÍ ÌÈÎÚ‹ Û˘ÏÏÔÁ‹ ˘ÊË·ÙÈο, ÂÚÈÛÏËÓÈο Î·È ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ˘ÔÁ·ÛÙÚ›Ô˘. ∆· ·ÓÙÈÛÒÌ·Ù· ÁÈ· ¯Ï·Ì‡‰È·, ÚÈΤÙÛȘ, ·‰ÂÓÔ˚Ô‡˜, EµV, CMV, ÈÔ‡˜ Echo Î·È Coxsackie, ‹Ù·Ó ·ÚÓËÙÈο, ÂÓÒ ÁÈ· ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ ‹Ù·Ó ıÂÙÈο: Igª 22 Î·È IgG 9,4. ªÂÙ¿ ·fi ‰‡Ô ‚‰ÔÌ¿‰Â˜ ‹Ù·Ó: IgM 23 Î·È IgG 38. °È· ÙËÓ ·Ó›¯Ó¢ÛË Î·È ÙÔÓ ÔÛÔÙÈÎfi ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙÔ˘ Ì˘ÎÔÏ¿ÛÌ·ÙÔ˜ Ù˘ Ó¢ÌÔÓ›·˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ÂÓ˙˘ÌÔ-·ÓÔÛÔ-ÚÔÛÚÔÊËÙÈ΋ ̤ıÔ‰Ô˜, fiÔ˘ Ù›ÙÏÔ˜ ÙˆÓ IgM ·ÓÙÈÛˆÌ¿ÙˆÓ ÌÂÁ·Ï‡ÙÂÚÔ˜ ÙÔ˘ 10 ıˆÚÂ›Ù·È ıÂÙÈÎfi˜. ªÂ ÙË ‰È¿ÁÓˆÛË Ù˘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜, ¤ÁÈÓ ‰È·ÎÔ‹ Ù˘ Û›ÙÈÛ˘, ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ Î·È Á·ÛÙÚÔÚÔÛÙ·Û›· Ì ÔÌÂÚ·˙fiÏË. ∂›Û˘ ÔÏÔÎÏËÚÒıËÎÂ Ë ·ÁˆÁ‹ Ì ÎÏ·Ú˘ıÚÔÌ˘Î›ÓË ÁÈ· 10 Ë̤Ú˜. ∏ ·Ì˘Ï¿ÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ ‚ÂÏÙÈÒıËÎÂ Î·È ·ÔηٷÛÙ¿ıËΠÛÙ· Ê˘ÛÈÔÏÔÁÈο fiÚÈ· ¤ÓÙ Ë̤Ú˜ ·ÚÁfiÙÂÚ·. ŒÁÈÓ ÛÙ·‰È·Î‹ Â·Ó·Û›ÙÈÛË Î·È Ô ·ÛıÂÓ‹˜ ÂÍ‹Ïı Û ηϋ ÁÂÓÈ΋ ηٿÛÙ·ÛË, ¯ˆÚ›˜ Û˘ÌÙÒÌ·Ù·.

™˘˙‹ÙËÛË ∏ ÔÍ›· ·ÁÎÚ·ٛÙȉ· ·ÔÙÂÏ› ¤Ó· Û¯ÂÙÈο Û¿ÓÈÔ ÓfiÛËÌ· ÛÙ· ·È‰È¿. ™ÙÔ˘˜ ·ÈÙÈÔÏÔÁÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ù˘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ ÛÙËÓ ·È‰È΋ ËÏÈΛ· ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È: ȉÈÔ·ı‹ ·›ÙÈ· (22%), ÙÚ·‡Ì· (20%), Ïԛ̈ÍË (15%), ÓfiÛÔ˜ ÙˆÓ ¯ÔÏËÊfiÚˆÓ (14%), Ê¿Ú̷η (13%), Û˘ÁÁÂÓ›˜ ·ÓˆÌ·Ï›Â˜ (5%), ‰È¿ÊÔÚ· ¿ÏÏ· ·›ÙÈ· (11%) (1,5). ∆Ô 1973, ÔÈ Leinikki et al ÂÚȤÁÚ·„·Ó ÚÒÙÔÈ ÂÚÈÙÒÛÂȘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ Ô˘ Û¯ÂÙÈ˙fiÙ·Ó Ì ·‡ÍËÛË ÙÔ˘ Ù›ÙÏÔ˘ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙÔ˘ Ì˘ÎÔÏ¿ÛÌ·ÙÔ˜ Ù˘ Ó¢ÌÔÓ›·˜ (6). ¶·ÚfiÌÔÈ· ·ÔÙÂϤÛÌ·Ù· ÂÍ¿ÁÔÓÙ·È Î·È ·fi ¿ÏϘ ÌÂϤÙ˜, fiÔ˘ ‚Ú¤ıËΠfiÙÈ ÙÔ 1/3 ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÍ›· ·ÁÎÚ·ٛÙȉ· ÂÌÊ¿ÓÈÛ·Ó ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙÔ˘ Ì˘ÎÔÏ¿ÛÌ·ÙÔ˜ Ù˘ Ó¢ÌÔÓ›·˜ (7,8). ŒÎÙÔÙÂ, Î·È ¿ÏÏÔÈ Û˘ÁÁÚ·Ê›˜ ¤¯Ô˘Ó ÂÚÈÁÚ¿„ÂÈ ÂÚÈÙÒÛÂȘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ ÛÙË ‰È·‰ÚÔÌ‹ Ïԛ̈͢ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡ ·fi Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ (1,4), ηıÒ˜ Î·È ÂÚÈÙÒÛÂȘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ Ì ·‡ÍËÛË ÙˆÓ ÂȉÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¯ˆÚ›˜ Û˘ÌÙÒÌ·Ù· ·fi ÙÔ ·Ó·Ó¢ÛÙÈÎfi (3). ™Â ‰È¿ÊÔÚ˜ ÌÂϤÙ˜ (4,7,8) ¤¯ÂÈ ÙÂı› ÙÔ ÂÚÒÙËÌ· Â¿Ó ·˘Ù‹ Ë ·‡ÍËÛË ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Û ·ÚÎÂÙ¤˜ ÂÚÈÙÒÛÂȘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜, ·Ô‰ÂÈÎÓ‡ÂÈ ÙËÓ ·ÈÙÈÔÏÔÁÈ΋ Û˘Û¯¤ÙÈÛË Ù˘ ÓfiÛÔ˘ Ì ÙË Ïԛ̈ÍË ·fi ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜ ‹ Â¿Ó Ù· ·ÓÙÈÛÒÌ·Ù· ·˘Ù¿ Â›Ó·È ÌË ÂȉÈο Î·È ÂÌÊ·Ó›˙ÔÓÙ·È ˆ˜ ·¿ÓÙËÛË Û ¿ÏÏ· ·ÓÙÈÁfiÓ·, fiˆ˜ Û˘ÛÙ·ÙÈο ·ÁÎÚ·ÙÈÎÒÓ ÈÛÙÒÓ ‹ ˆ˜ ‰È·ÛÙ·˘ÚÔ‡ÌÂÓË ·ÓÙ›‰Ú·ÛË Û ¿ÏÏÔ Ì˘ÎfiÏ·ÛÌ· Ô˘ ÚÔηÏ› ÙË ÓfiÛÔ. øÛÙfiÛÔ, Ë ÂΉ‹ÏˆÛË ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ ÛÙË ‰È·‰ÚÔÌ‹ Ó¢ÌÔÓ›·˜, fiˆ˜ ÛÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ Ì·˜, ηıÈÛÙ¿ ·›ı·ÓË ÙËÓ ˘fiıÂÛË fiÙÈ Ë ·‡ÍËÛË ÙˆÓ ÂȉÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÁÈ· ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜, Â›Ó·È ÌË ÂȉÈ΋. √ ÌÈÎÚÔÔÚÁ·ÓÈÛÌfi˜ ‰ÂÓ ¤¯ÂÈ ·ÔÌÔÓˆı› ·fi ·ÁÎÚ·ÙÈÎfi ÈÛÙfi Î·È Ë ·ÈÙÈÔÏÔÁÈ΋ ÙÔ˘ Û˘Û¯¤ÙÈÛË Ì ÙËÓ ÔÍ›· ·ÁÎÚ·ٛÙȉ· ‚·Û›˙ÂÙ·È Û ÌÂÌÔӈ̤Ó˜ ·Ó·ÊÔÚ¤˜ ÂÚÈÙÒÛÂˆÓ Î·È ÛÙÔÓ ÔÚÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô ÙˆÓ ·ÛıÂÓÒÓ (1). ∞˘Ùfi ÔÊ›ÏÂÙ·È ÂÓ Ì¤ÚÂÈ ÛÙÔ Ôχ ÌÈÎÚfi ̤ÁÂıÔ˜ ÙÔ˘ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡ (<350 Ìm Ì‹ÎÔ˜) Ô˘ ÙÔÓ Î·ıÈÛÙ¿ ÌË ÔÚ·Ùfi ÛÙÔ ÊˆÙÂÈÓfi ÌÈÎÚÔÛÎfiÈÔ. ∂ÈϤÔÓ, ·ÓÙ›ıÂÙ· Ì ٷ ¿ÏÏ· ›‰Ë Ì˘ÎÔÏ¿ÛÌ·ÙÔ˜, ·Ó·Ù‡ÛÛÂÙ·È Ôχ ·ÚÁ¿ Î·È ··ÈÙÔ‡ÓÙ·È 1-3 ‚‰ÔÌ¿‰Â˜ ÁÈ· ÙË ‰ËÌÈÔ˘ÚÁ›· ·ÔÈÎÈÒÓ (1). ∏ ̤ıÔ‰Ô˜ PCR, Ô˘ ¤¯ÂÈ ¶·È‰È·ÙÚÈ΋ 2006;69:310-312

312

¶. ¡ÂÔÓ¿ÎË Î·È Û˘Ó.

ÂÊ·ÚÌÔÛÙ› ÚfiÛÊ·Ù· Û ‰Â›ÁÌ·Ù· Ê·Ú˘ÁÁÈÎÔ‡ ÂȯڛÛÌ·ÙÔ˜, ı· ‹Ù·Ó ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚË ÁÈ· ¿ÌÂÛË Ù·˘ÙÔÔ›ËÛË ÙÔ˘ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡. ¶·Ú¤¯ÂÈ ÁÚ‹ÁÔÚ· ·ÔÙÂϤÛÌ·Ù·, Û 2-5 Ë̤Ú˜, ÂÓÒ ·ÓȯÓ‡ÂÈ Î·È ÓÂÎÚÔ‡˜ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜, Û ÂÚ›ÙˆÛË Ô˘ Ô ·ÛıÂÓ‹˜ ¤¯ÂÈ ·Ú¯›ÛÂÈ ıÂÚ·›· (2). ∏ ‰È¿ÁÓˆÛË Ù˘ ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜ ‚·Û›˙ÂÙ·È ÛÙÔÓ Û˘Ó‰˘·ÛÌfi Ù˘ ÎÏÈÓÈ΋˜ ÂÈÎfiÓ·˜, ÙˆÓ ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ÂÍÂÙ¿ÛÂˆÓ Î·È ÙÔ˘ ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂϤÁ¯Ô˘. ™ÙËÓ ÂÚ›ÙˆÛ‹ Ì·˜ Ë ‰È¿ÁÓˆÛË ‚·Û›ÛÙËΠÛÙ· Û˘ÌÙÒÌ·Ù· ÙÔ˘ ·ÛıÂÓÔ‡˜ ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi, ÛÙËÓ ·‡ÍËÛË Ù˘ ·Ì˘Ï¿Û˘ ¿Óˆ ·fi ÙÔ ÙÚÈÏ¿ÛÈÔ (Ë ·‡ÍËÛË Ù˘ ·Ì˘Ï¿Û˘ ÔÚÔ‡ >3-6 ÊÔÚ¤˜ ¿Óˆ ·fi ÙË Ê˘ÛÈÔÏÔÁÈ΋ ÙÈÌ‹ ıˆÚÂ›Ù·È fiÙÈ ·˘Í¿ÓÂÈ ÙËÓ ÂȉÈÎfiÙËÙ· ‰È¿ÁÓˆÛ˘ >92%) Î·È ÛÙ· ¤ÌÌÂÛ· ·ÂÈÎÔÓÈÛÙÈο Â˘Ú‹Ì·Ù·. ∏ ·ÈÙÈÔÏÔÁÈ΋ ‰È¿ÁÓˆÛË ‚·Û›ÛÙËΠÛÙËÓ ·‡ÍËÛË ÙˆÓ IgM Î·È ÛÙÔÓ ÙÂÙÚ·Ï·ÛÈ·ÛÌfi ÙˆÓ IgG ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙÔ˘ Ì˘ÎÔÏ¿ÛÌ·ÙÔ˜ Ù˘ Ó¢ÌÔÓ›·˜, ÂÓÒ ·ÔÎÏ›ÛÙËÎ·Ó ¿ÏÏ· Èı·Ó¿ ·›ÙÈ· ÔÍ›·˜ ·ÁÎÚ·ٛÙȉ·˜. ªÂÚÈÎÔ› Û˘ÁÁÚ·Ê›˜ ÚÔÙ›ÓÔ˘Ó ˆ˜ Èı·Ófi ·ıÔÁÂÓÂÙÈÎfi Ì˯·ÓÈÛÌfi ÙÔ Ô›‰ËÌ· ÙÔ˘ ʇ̷ÙÔ˜ ÙÔ˘ Vater, ÏfiÁˆ Ù˘ Ïԛ̈͢ ·fi ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜, Î·È ÙËÓ ·‡ÍËÛË Ù˘ Û˘ÁΤÓÙÚˆÛ˘ Ù˘ ·ÁÎÚ·ÙÈ΋˜ Ï˘ÛÔÏÂÎÈı›Ó˘ ÛÙÔ˘˜ ·ÁÎÚ·ÙÈÎÔ‡˜ fiÚÔ˘˜, Ë ÔÔ›· ¤¯ÂÈ ÁÓˆÛÙ‹ ΢ÙÙ·ÚÔÙÔÍÈ΋ ‰Ú¿ÛË. ÕÏÏÔÈ ıˆÚÔ‡Ó Èı·Ó‹ ÙËÓ ·Ú·ÁˆÁ‹ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Ô˘ ·ÓÙȉÚÔ‡Ó Ì ¤Ó· ·ÁÎÚ·ÙÈÎfi ·ÓÙÈÁfiÓÔ, fiˆ˜ ¤¯ÂÈ ÚÔÙ·ı› Î·È ÁÈ· ÂΉËÏÒÛÂȘ ·fi ¿ÏÏ· Û˘ÛÙ‹Ì·Ù· (1,2,4). √ ¿ÌÂÛÔ˜ ÂÓÔÊı·ÏÌÈÛÌfi˜ ÙˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ ÛÙÔ ÚÔۂ‚ÏË̤ÓÔ fiÚÁ·ÓÔ ıˆÚÂ›Ù·È Â›Û˘ Èı·Ófi˜ ·ıÔÁÂÓÂÙÈÎfi˜ Ì˯·ÓÈÛÌfi˜ (1,2).

¶·È‰È·ÙÚÈ΋ 2006;69:310-312

™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ, ÔÈ Â͈Ó¢ÌÔÓÈΤ˜ ÂΉËÏÒÛÂȘ ·ÎÔÏÔ˘ıÔ‡Ó Ù· Û˘ÌÙÒÌ·Ù· ·fi ÙÔ ·Ó·Ó¢ÛÙÈÎfi Î·È Ë ıÂÚ·›· Ì ̷ÎÚÔÏ›‰Â˜ ‹ ÙÂÙڷ΢ÎÏ›ÓË ÂÏ¿¯ÈÛÙ· ÌÔÚ› Ó· ÂËÚ¿ÛÂÈ ÙËÓ ÔÚ›· Ù˘ Â͈Ó¢ÌoÓÈ΋˜ ÓfiÛÔ˘ (1). ™˘ÌÂÚ·ÛÌ·ÙÈο, fiÙ·Ó ÛÙË ‰È·‰ÚÔÌ‹ ¿Ù˘˘ Ó¢ÌÔÓ›·˜ ÂÌÊ·ÓÈÛÙÔ‡Ó Û˘ÌÙÒÌ·Ù· ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi, ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÙ·È Ë ÔÍ›· ·ÁÎÚ·ٛÙȉ· ˆ˜ Â͈Ó¢ÌÔÓÈ΋ ÂΉ‹ÏˆÛË ·fi ÙÔ Ì˘ÎfiÏ·ÛÌ· Ù˘ Ó¢ÌÔÓ›·˜.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Al-Abasi ∞. Acute pancreatitis associated with Mycoplasma pneumoniae: a case report of missed diagnosis. Med Princ Pract 2002;11:112-115.

2. Berger RP, Wadowksy RM. Rhabdomyolysis associated with infection by Mycoplasma pneumoniae: a case report. Pediatrics 2000;105:433-436.

3. Handrick W, Braun W, Hofmann V, Senger H, Spencker FB. Mycoplasma etiology of acute pancreatitis. Z Gesamte Inn Med 1986;41:611-612.

4. Herbaut C, Tielemans C, Burette A, Dratwa M. Mycoplasma pneumoniae infection and acute pancreatitis. Acta Clin Belg 1983;38:186-188.

5. Pietzak MM, Thomas DW. Pancreatitis in childhood. Pediatr Rev 2000;21:406-441.

6. Leinikki PO, Panzar P, Tykka H. Antibody response in patients with acute pancreatitis to Mycoplasma pneumoniae. Scand J Gastroenterol 1973;8:631-635.

7. Leinikki OP, Panzar P, Tykka H. Immunoglobulin M antibody response against Mycoplasma pneumoniae lipid antigen in patients with acute pancreatitis.

J Clin Microbiol 1978;8:113-118.

8. Freeman R, McMahon MJ. Acute pancreatitis and serological evidence of infection with Mycoplasma pneumoniae. Gut 1978;19:367-370.

∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏

CASE REPORT

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∞˘¯ÂÓÈÎfi ÏÈÔ‚Ï¿Ûو̷ Û ‚Ú¤ÊÔ˜: Ì›· Û¿ÓÈ· ÎÏÈÓÈ΋ ÔÓÙfiÙËÙ· Õ. ∆Û·ÏΛ‰Ë˜1, ™. °·Ú‰›Î˘2, ∏. ∫·Ú·¿ÓÙ˙Ô˜3, ∫. ∫·ÌÔ‡ÚË2, ™. ¢Â˘ÙÂÚ·›Ô˜4, ∞. °È·ÙÚÔ̷ӈϿÎË5, ∂. ™È‚Ú›‰Ë˜5, ∞. ÷Ù˙ËÌȯ·‹Ï1

¶ÂÚ›ÏË„Ë: ∆Ô ÏÈÔ‚Ï¿Ûو̷ Â›Ó·È ¤Ó·˜ Û¿ÓÈÔ˜ ηÏÔ‹ı˘ fiÁÎÔ˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜, Ô ÔÔ›Ô˜ ÚÔ¤Ú¯ÂÙ·È ·fi ÂÌ‚Ú˘˚Îfi Ï›Ô˜. ™ÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· ¤¯Ô˘Ó ηٷÁÚ·Ê› ÌfiÓÔ 14 ÂÚÈÙÒÛÂȘ ÙÚ·¯ËÏÈÎÔ‡ ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜. ™ÙËÓ ·ÚÔ‡Û· ÂÚÁ·Û›· ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ë ÂÚ›ÙˆÛË ‚Ú¤ÊÔ˘˜ Ì ÏÈÔ‚Ï¿Ûو̷ ÛÙËÓ ·˘¯ÂÓÈ΋ ¯ÒÚ·. ∫ÔÚ›ÙÛÈ ËÏÈΛ·˜ 9 ÌËÓÒÓ ·ÚÔ˘Û›·Û ̷Ïı·Î‹, ·ÓÒ‰˘ÓË Ì¿˙·, ηٿ ÙËÓ Ô›ÛıÈ· ÙÚ·¯ËÏÈ΋ ¯ÒÚ·. ∆Ô ‚Ú¤ÊÔ˜ ÚÔ¤‚Ë Û ¤ÏÂÁ¯Ô Ì US, CT Î·È MRI. ∏ ·ÛıÂÓ‹˜ ˘Ô‚Ï‹ıËΠ۠Ï‹ÚË ÂÎÙÔÌ‹ Ù˘ Ì¿˙·˜. ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· Ù˘ ·ÛıÂÓÔ‡˜ ˘‹ÚÍ ÔÌ·Ï‹ Î·È ·Ú·Ì¤ÓÂÈ Û ‡ÊÂÛË ÌÂÙ¿ ·fi 22 Ì‹Ó˜. ∏ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË ÙÔ˘ fiÁÎÔ˘ ¤‰ÂÈÍ ÙËÓ Ù˘È΋ ÂÈÎfiÓ· ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜. ∆Ô ÏÈÔ‚Ï¿Ûو̷ ·ÔÙÂÏ› ¤Ó· Û¿ÓÈÔ ·›ÙÈÔ ‰ÈfiÁΈÛ˘ ÛÙËÓ ÙÚ·¯ËÏÈ΋ ¯ÒÚ·, Ô˘ Ú¤ÂÈ fï˜ Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË. £ÂÚ·›· ÂÎÏÔÁ‹˜ ·ÔÙÂÏ› Ë Ï‹Ú˘ ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÎÙÔÌ‹ Ù˘ Ì¿˙·˜, ÒÛÙ ӷ ÌËÓ ˘¿Ú¯ÂÈ ÂӉ¯fiÌÂÓÔ ˘ÔÙÚÔ‹˜. §¤ÍÂȘ ÎÏÂȉȿ: §ÈÔ‚Ï¿Ûو̷, ·È‰È¿, ÙÚ·¯ËÏÈ΋ ¯ÒÚ·.

¶ÂÚÈÊÂÚÂÈ·Îfi °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∞ÏÂÍ·Ó‰ÚÔ‡ÔÏ˘ 1 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¢ËÌÔÎÚ›ÙÂÈÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ £Ú¿Î˘ 2 ¶·È‰Ô¯ÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ¢ËÌÔÎÚ›ÙÂÈÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ £Ú¿Î˘ 3 øÙÔÚÈÓÔÏ·Ú˘ÁÁÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ¢ËÌÔÎÚ›ÙÂÈÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ £Ú¿Î˘ 4 ∞ÎÙÈÓÔÏÔÁÈÎfi ∆Ì‹Ì· 5 ¶·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎfi ∆Ì‹Ì· ¢ËÌÔÎÚ›ÙÂÈÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ £Ú¿Î˘ AÏÏËÏÔÁÚ·Ê›·: ÕÁÁÂÏÔ˜ ∆Û·ÏΛ‰Ë˜ ∫. ¶·Ï·ÈÔÏfiÁÔ˘ 59 ∆.∫. 681 00, ∞ÏÂÍ·Ó‰ÚÔ‡ÔÏË E-mail: atsalkid@med.duth.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 17-05-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 19-05-2006

Posterior cervical lipoblastoma: a rare neck mass in childhood A. Tsalkidis1, S. Gardikis2, E. Karapantzos3, K. Kabouri2, S. Deftereos4, A. Giatromanolaki5, E. Sibridis5, A. Chatzimichael1

Abstract: Lipoblastoma is a rare benign childhood tumour derived from embryonic fat, and only 14 cases of cervical lipoblastoma have been documented. The case is reported of a healthy 9 month-old girl with a posterior cervical lipoblastoma, who presented with a firm, posterior cervical mass. After evaluation by US, CT and MRI the tumour was completely resected. Histological examination of the resected tissue showed the typical pattern of lipoblastoma. The child’s postoperative progress was uneventful and she remained in remission 22 months after surgery. Lipoblastoma must be included in the differential diagnosis of cervical masses in childhood. The treatment of choice is complete surgical resection, in order to prevent local recurrence.

Correspondence: Aggelos Tsalkidis 59, C. Paleologou Str. 681 00, Alexandroupolis E-mail: atsalkid@med.duth.gr

Key words: Lipoblastoma, childhood, neck.

™˘ÓÙÔÌÔÁڷʛ˜ US ÀÂÚ˯ÔÁÚ¿ÊËÌ· CT ÀÔÏÔÁÈÛÙÈ΋ ÙÔÌÔÁÚ·Ê›· MRI ª·ÁÓËÙÈÎfi˜ Û˘ÓÙÔÓÈÛÌfi˜

∂ÈÛ·ÁˆÁ‹ ∆Ô ÏÈÔ‚Ï¿Ûو̷ Â›Ó·È ¤Ó·˜ ηÏÔ‹ı˘ ÌÂÛÂÁ¯˘Ì·ÙÈÎfi˜ fiÁÎÔ˜ ÙˆÓ ÂÌ‚Ú˘˚ÎÒÓ ÏÈÔÂȉÒÓ Î˘ÙÙ¿ÚˆÓ (1-3). ∆· ·ÁfiÚÈ· ÚÔÛ‚¿ÏÏÔÓÙ·È ÂÚÈÛÛfiÙÂÚÔ Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ· Û ·Ó·ÏÔÁ›· 3:1 (1,3,4). ∏ Û˘¯ÓfiÙÂÚË ÂÓÙfiÈÛ‹ ÙÔ˘ Â›Ó·È ÛÙ· ¿ÎÚ· Î·È ÛÙÔÓ ÎÔÚÌfi ÙÔ˘ ÛÒÌ·ÙÔ˜ (1,2). ™¿ÓÈ· ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ÎÂÊ·-

Peripheral General Hospital of Alexandroupolis 1 Paediatric Clinic of Democritus University of Thrace 2 Department of Paediatric Surgery of Democritus University of Thrace 3 Otorhinolaryngology Clinic of Democritus University of Thrace 4 Department of Radiology 5 Department of Pathology of Democritus University of Thrace

Ï‹˜ Î·È ÙÔ˘ ÙÚ·¯‹ÏÔ˘ (2). ªfiÓÔ 14 ÂÚÈÙÒÛÂȘ ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜ ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÙÚ·¯‹ÏÔ˘ ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· (4). ∏ Ï‹Ú˘ ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ù˘ Ì¿˙·˜ ·ÔÙÂÏ› ÙË ıÂÚ·›· ÂÎÏÔÁ‹˜ (1). ™ÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙˆÓ ‰ÈÔÁÎÒÛÂˆÓ ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÙÚ·¯‹ÏÔ˘ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ‰È¿ÊÔÚÔÈ Î·ÎÔ‹ıÂȘ fiÁÎÔÈ fiˆ˜ ÏÈÔÛ¿ÚΈ̷, Ó¢ÚÔ‚Ï¿Ûو̷, Ú·‚‰ÔÌ˘ÔÛ¿ÚΈ̷, ÈÛÙÈÔ·ÙÙˆÛË Ã Î·È non-Hodgkin ϤÌʈ̷, ·ÏÏ¿ Î·È Î·ÏÔ‹ıÂȘ fiÁÎÔÈ fiˆ˜ ÙÂڿو̷, ÏÂÌÊ·ÁÁ›ˆÌ· Î·È ·ÈÌ·ÁÁ›ˆÌ·. ¶ÂÚÈÁÚ¿ÊÂÙ·È Ë ÂÚ›ÙˆÛË ‚Ú¤ÊÔ˘˜ Ô˘

Date of submission: 17-05-2005 Date of approval: 19-05-2006

¶·È‰È·ÙÚÈ΋ 2006;69:313-316

314

Õ. ∆Û·ÏΛ‰Ë˜ Î·È Û˘Ó.

·ÚÔ˘Û›·˙ ÏÈÔ‚Ï¿Ûو̷ ÛÙËÓ Ô›ÛıÈ· ÙÚ·¯ËÏÈ΋ ¯ÒÚ·, ·ÊÂÓfi˜ ÏfiÁˆ Ù˘ ÂÍ·ÈÚÂÙÈ΋˜ Û·ÓÈfiÙËÙ·˜ Ù˘ ÂÓÙfiÈÛ‹˜ ÙÔ˘ Î·È ·ÊÂÙ¤ÚÔ˘ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂÈÛËÌ·Óı› fiÙÈ Ú¤ÂÈ Ó· ηıÔÚ›˙ÂÙ·È Ë ·ÎÚÈ‚‹˜ ʇÛË Ù˘ ‰ÈfiÁΈÛ˘ ·Ó·ÙÔÌÈο Î·È ÈÛÙÔ·ıÔÏÔÁÈο, ÒÛÙ ӷ ÂÈϤÁÂÙ·È Ë Î·Ù¿ÏÏËÏË ıÂÚ·›·.

¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ¶ÚfiÎÂÈÙ·È ÁÈ· ÎÔÚ›ÙÛÈ, ÙÔ ÌÔÓ·‰ÈÎfi Ù˘ ÔÈÎÔÁ¤ÓÂÈ·˜, ÙÔ ÔÔ›Ô ÁÂÓÓ‹ıËΠÌÂÙ¿ ·fi Ê˘ÛÈÔÏÔÁÈ΋ ·ËÛË Î·È ÙÔÎÂÙfi, Ì ‚¿ÚÔ˜ Á¤ÓÓËÛ˘ 3260 g. ™Â ËÏÈΛ· 8 ÌËÓÒÓ ÔÈ ÁÔÓ›˜ ·ÓÙÈÏ‹ÊıËÎ·Ó ÙËÓ ‡·ÚÍË ‰ÈfiÁΈÛ˘ ηٿ ÙËÓ Ô›ÛıÈ· ÙÚ·¯ËÏÈ΋ ¯ÒÚ·, ¯ˆÚ›˜ ¿ÏÏË Û˘ÓÔ‰fi Û˘Ìو̷ÙÔÏÔÁ›·. ∫·Ù¿ ÙËÓ ÎÏÈÓÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËÎÂ Ë ‡·ÚÍË Ì›·˜ Ì·Ïı·Î‹˜, ·ÓÒ‰˘Ó˘ Ì¿˙·˜ Ì ÂÏ·ÛÙÈÎfiÙËÙ· ÛÙËÓ ›ÂÛË, ηٿ ÙËÓ Ô›ÛıÈ· ÙÚ·¯ËÏÈ΋ ¯ÒÚ·, ‰È·ÛÙ¿ÛÂˆÓ 4x3 cm. ∆Ô ˘ÂÚΛÌÂÓÔ ‰¤ÚÌ· ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈÎfi, ¯ˆÚ›˜ ÛÙÔȯ›· ÊÏÂÁÌÔÓ‹˜. ∏ ·Ú¯È΋ ÂͤٷÛË Ì ˘¤ÚË¯Ô˘˜ (US) ·Ó¤‰ÂÈÍ ÙËÓ ·ÚÔ˘Û›· ÔÌÔÈÔÁÂÓÔ‡˜ Ì¿˙·˜ Ì ˯ÔÁ¤ÓÂÈ· ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡, ‰È·ÛÙ¿ÛÂˆÓ 4,4x3,8x2,1 cm. ªÂ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ ÏÈÒÌ·ÙÔ˜ ÙÔ ·È‰› Â¤ÛÙÚ„ ÛÙÔ Û›ÙÈ ÙÔ˘ Î·È Û˘ÓÂÛÙ‹ıË Â·ÓÂͤٷÛË ÌÂÙ¿ 2 ‚‰ÔÌ¿‰Â˜. ∫·Ù¿ ÙËÓ Â·ÓÂͤٷÛË ‰È·ÈÛÙÒıËΠ¿ÏÈ Ë Ì¿˙· Ì ÙÔ˘˜ ›‰ÈÔ˘˜ ¯·Ú·ÎÙ‹Ú˜, ÏËÓ fï˜ ˘‹ÚÍ ·‡ÍËÛË ÙˆÓ ‰È·ÛÙ¿ÛÂÒÓ Ù˘ (6x4 cm) (∂ÈÎfiÓ· 1). √ Â·Ó¤ÏÂÁ¯Ô˜ Ì US ÂȂ‚·›ˆÛ ÙËÓ ÎÏÈÓÈ΋ ÂÎÙ›ÌËÛË, Û‡Ìʈӷ Ì ÙÔÓ ÔÔ›Ô Ë Ì¿˙· ›¯Â ‰È·ÛÙ¿ÛÂȘ 6,7x4,6x3,3 cm. ∆o ÎÔÚ›ÙÛÈ ÂÈÛ‹¯ıË ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô Î·È ˘Ô‚Ï‹ıËΠ۠ÂͤٷÛË Ì ˘ÔÏÔÁÈÛÙÈ΋ ÙÔÌÔÁÚ·Ê›· (CT) ·˘¯¤ÓÔ˜. ∞˘Ù‹ ·Ó¤‰ÂÈÍ ̿˙· ˘fi ÙÔ˘ ÙÚ·Â˙ÔÂȉԇ˜ Ì˘fi˜, ·ÚÈÛÙÂÚ¿ Î·È ‰ÂÍÈ¿ Ù˘ ̤Û˘ ÁÚ·ÌÌ‹˜ Û Â·Ê‹

∂ÈÎfiÓ· 1. ∂ÈÛÎÔÈ΋ ÂÈÎfiÓ· Ù˘ Ì¿˙·˜. ¶·È‰È·ÙÚÈ΋ 2006;69:313-316

Ì ٷ ÙfiÍ· ÙˆÓ ·˘¯ÂÓÈÎÒÓ ÛÔÓ‰‡ÏˆÓ, Ì ˘ÎÓfiÙËÙ˜ Ï›Ô˘˜ Î·È ÔÏÏ·Ï¿ ‰È·ÊÚ·ÁÌ¿ÙÈ·. §fiÁˆ ÙÔ˘ ÌË Ù˘ÈÎÔ‡ ÙˆÓ ·ÂÈÎÔÓÈÛÙÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ Î·È ÁÈ· ÙÔÓ ·ÎÚÈ‚‹ ηıÔÚÈÛÌfi Ù˘ Û˘Û¯¤ÙÈÛ˘ Ù˘ Ì¿˙·˜ Ì ÙÔÓ ÛÔÓ‰˘ÏÈÎfi ۈϋӷ, ˘Ô‚Ï‹ıËΠ۠ÂÚ·ÈÙ¤Úˆ ¤ÏÂÁ¯Ô Ì ̷ÁÓËÙÈÎfi Û˘ÓÙÔÓÈÛÌfi (MRI). ¢È·ÈÛÙÒıËÎÂ Ë Û˘ÁÎÂÎÚÈ̤ÓË Ì¿˙·, ÂÂÎÙÂÈÓfiÌÂÓË ·fi ÙÔ ‡„Ô˜ ÙÔ˘ £1 ÛÔÓ‰‡ÏÔ˘ ̤¯ÚÈ ÙÔ ÈÓÈ·Îfi fiÁΈ̷ ‰È·ÛÙ¿ÛÂˆÓ 7 cm (ÂÁοÚÛÈ·) x 5 cm (ÎÂÊ·ÏÔ˘Ú·›·) x 3,5 cm (ÚÔÛıÈÔ›ÛıÈ·), ÌË Û¯ÂÙÈ˙fiÌÂÓË Ì ÙÔÓ ÛÔÓ‰˘ÏÈÎfi ۈϋӷ Î·È ÂÚÈ‚·ÏÏfiÌÂÓË ·fi ÈÓÒ‰Ë Î¿„· (∂ÈÎfiÓ· 2). ªÂ ÙÔÌ‹ ÂÁοÚÛÈ· Ô›ÛıÈ· ÙÚ·¯ËÏÈ΋, Ë Ì¿˙· ÂÍ·ÈÚ¤ıËΠÔÏÔÎÏËÚˆÙÈο (∂ÈÎfiÓ· 3). √È Ú·ÁÌ·ÙÈΤ˜ ‰È·ÛÙ¿ÛÂȘ ÌÂÙ¿ ÙËÓ ÂÍ·›ÚÂÛ‹ Ù˘ ‹Ù·Ó 7x5x4 cm. ∏ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË ÙÔ˘ ·Ú·Û΢¿ÛÌ·ÙÔ˜ ¤‰ÂÈÍ ηÏfiËı˜ ÏÈÔ‚Ï¿Ûو̷ (∂ÈÎfiÓ· 4). ∏ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÔÚ›· Ù˘ ·ÛıÂÓÔ‡˜ ˘‹ÚÍ ÔÌ·Ï‹ Î·È ÙÔ ·È‰› ÂÍ‹Ïı ·fi ÙÔ ÓÔÛÔÎÔÌÂ›Ô ÙËÓ 4Ë ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ë̤ڷ. ∆Ô ÎÔÚ›ÙÛÈ ·Ú·ÎÔÏÔ˘ıÂ›Ù·È 22 Ì‹Ó˜ ÌÂÙÂÁ¯ÂÈÚËÙÈο Î·È ‰ÂÓ ¤¯ÂÈ ‰È·ÈÛÙˆı› ˘ÔÙÚÔ‹ Ù˘ ‚Ï¿‚˘.

∂ÈÎfiÓ· 2. (MRI ÙÚ·¯ËÏÈ΋˜ ¯ÒÚ·˜). ∏ Ì¿˙· ÂÎÙ›ÓÂÙ·È ·fi ÙÔÓ ÛfiÓ‰˘ÏÔ £1 ¤ˆ˜ ÙÔ ÈÓÈ·Îfi fiÁΈ̷, ÌË Û¯ÂÙÈ˙fiÌÂÓË Ì ÙÔÓ ÛÔÓ‰˘ÏÈÎfi ۈϋӷ.

315

∞˘¯ÂÓÈÎfi ÏÈÔ‚Ï¿Ûو̷

∂ÈÎfiÓ· 3. ∏ Ì¿˙· ÌÂÙ¿ ÙËÓ ÂÎÙÔÌ‹ Ù˘.

∂ÈÎfiÓ· 4. πÛÙÔÏÔÁÈÎfi ·Ú·Û··ÛÌ· ÙÔ˘ ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜.

™˘˙‹ÙËÛË √ fiÚÔ˜ ÏÈÔ‚Ï¿Ûو̷ ¯ÚËÛÈÌÔÔÈ‹ıËΠ·Ú¯Èο ÙÔ 1926 ·fi ÙÔÓ Jaffe RH (5), ÁÈ· Ó· ÂÚÈÁÚ¿„ÂÈ ¤Ó·Ó fiÁÎÔ ·fi ·ÓÒÚÈÌ· ÏÈÒ‰Ë Î‡ÙÙ·Ú· Ù˘ ‚Ô˘‚ˆÓÈ΋˜ ¯ÒÚ·˜ Î·È ÛÙË Û˘Ó¤¯ÂÈ·, ÙÔ 1958, Ô fiÚÔ˜ ÏÈÔ‚Ï·Ûو̿وÛË ·fi ÙÔ˘˜ Vellios Î·È Û˘Ó (6). √È fiÁÎÔÈ ÙÔ˘ ÂÌ‚Ú˘˚ÎÔ‡ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ Â›Ó·È Ôχ Û¿ÓÈÔÈ. ∂ÌÊ·Ó›˙ÔÓÙ·È Û˘Ó‹ıˆ˜ ÛÙ· ‚Ú¤ÊË Î·È ÛÙ· ·È‰È¿, ÚÔÂÚ¯fiÌÂÓÔÈ ·fi ÙÔÓ Û˘Ó¯‹ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ ÏÈÔ‚Ï·ÛÙÒÓ Î·Ù¿ ÙËÓ ÂÚ›Ô‰Ô ÌÂÙ¿ ÙË Á¤ÓÓËÛË. À¿Ú¯Ô˘Ó ΢ڛˆ˜ ‰‡Ô ÎÏÈÓÈÎÔ·ıÔÏÔÁÈÎÔ› Ù‡ÔÈ: ·) ÙÔ ÏÈÔ‚Ï¿Ûو̷, Ô˘ Â›Ó·È Ô Û˘ÓËı¤ÛÙÂÚÔ˜ Ù‡Ô˜, ÂÓÙÔÈṲ̂ÓÔ˜ Î·È Î·Ï¿ ÂÚÈÁÂÁÚ·Ì̤ÓÔ˜, ‚) Ë ÏÈÔ‚Ï·Ûو̿وÛË, Ô˘ Â›Ó·È Ô ‰È¿¯˘ÙÔ˜ Ù‡Ô˜, ·Û·ÊÒ˜ ηıÔÚÈṲ̂ÓÔ˜, Ì ٿÛË Ó· ·˘Í¿ÓÂÈ ÙË Ì¿˙· ÙÔ˘ ÂÓÙfi˜ ÙˆÓ ·Ú·Î›ÌÂÓˆÓ ÈÛÙÒÓ Î·È ÙˆÓ Ì˘ÒÓ (1-3). √È ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ·ÊÔÚÔ‡Ó Û ·È‰È¿ ËÏÈΛ·˜ ÌÈÎÚfiÙÂÚ˘ ÙˆÓ 3 ÂÙÒÓ (1,2). ™Ù· 2/3 ÙˆÓ ÂÚÈÙÒÛˆÓ, ÙÔ Ù˘ÈÎfi ÏÈÔ‚Ï¿Ûو̷ ÂÓÙÔ›˙ÂÙ·È ÛÙ· ¿ÎÚ· (1,2) Î·È ÛÙÔÓ ÎÔÚÌfi, ÂÓÒ Ë ÂÓÙfiÈÛË ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÙÚ·¯‹ÏÔ˘ Â›Ó·È ÂÍ·ÈÚÂÙÈο Û¿ÓÈ· (2) Î·È Ì¤¯ÚÈ

Û‹ÌÂÚ· ÌfiÓÔ 14 ÂÚÈÙÒÛÂȘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· (7). ∏ ·ÚÔ‡Û· ÂÚ›ÙˆÛË ·ÔÙÂÏ› ÙËÓ ÚÒÙË ·Ó·ÊÔÚ¿ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· fiÔ˘ Ë ‚Ï¿‚Ë ÂÓÙÔ›˙ÂÙ·È ÛÙËÓ Ô›ÛıÈ· ÙÚ·¯ËÏÈ΋ ¯ÒÚ·. ∏ ·ÎÚÈ‚‹˜ ÎÏÈÓÈ΋ ÂÓÙfiÈÛË (·ÔÙ‡ˆÛË) Â›Ó·È ‰‡ÛÎÔÏË Î·È ÔÈ ·ÂÈÎÔÓÈÛÙÈΤ˜ ̤ıÔ‰ÔÈ Â›Ó·È ·ÓÂ·ÚΛ˜ ÁÈ· ÙËÓ ·ÎÚÈ‚‹ ‰È¿ÁÓˆÛË. ∞ÎÙÈÓÔÏÔÁÈο, ÙÔ ÏÈÔ‚Ï¿Ûو̷ ÂÌÊ·Ó›˙ÂÙ·È Û·Ó ÌË Û˘ÁÎÂÎÚÈ̤ÓË Ì¿˙· ‹È·˜ ÈÛÙÈ΋˜ ˘ÎÓfiÙËÙ·˜ (1,2). ™ÙÔ US ÙÔ ÏÈÔ‚Ï¿Ûو̷ ·ÚÔ˘ÛÈ¿˙ÂÙ·È Û·Ó Ì¿˙· ÌÂÈÎÙ‹˜ ˯ÔÁ¤ÓÂÈ·˜ (1). ∏ ÂͤٷÛË Ì CT Û˘¯Ó¿ ÂȂ‚·ÈÒÓÂÈ ÙËÓ ˘ÎÓfiÙËÙ· Ï›Ô˘˜ ÙÔ˘ fiÁÎÔ˘, Ô ÔÔ›Ô˜ ‰È·¯ˆÚ›˙ÂÙ·È ·fi Â·¯˘Ṳ̂ӷ ‰È·ÊÚ·ÁÌ¿ÙÈ·. √È ·ÂÈÎÔÓ›ÛÂȘ Ù˘ CT Î·È MRI ÂÈÙÚ¤Ô˘Ó ÙËÓ ·ÎÚÈ‚‹ ·ÍÈÔÏfiÁËÛË Ù˘ ı¤Û˘ Î·È ÙÔ˘ ÌÂÁ¤ıÔ˘˜ ÙÔ˘ fiÁÎÔ˘ Î·È ÌÔÚÔ‡Ó Ó· ·Ôηχ„Ô˘Ó ÙÔÓ ÏÔ‚Ò‰Ë Î·È ÏÈÒ‰Ë ¯·Ú·ÎÙ‹Ú· ÙÔ˘ (1,2). ™ÙËÓ ÂÚ›ÙˆÛË Ù˘ ÏÈÔ‚Ï·Ûو̿وÛ˘, Ë Ì¿˙· ‰ÂÓ Â›Ó·È Û·ÊÒ˜ ηıÔÚÈṲ̂ÓË ·fi ÙÔ˘˜ ·Ú·Î›ÌÂÓÔ˘˜ ÈÛÙÔ‡˜ ηٿ ÙËÓ ·ÂÈÎfiÓÈÛË Ù˘ MRI (2). ∏ ÙÂÏÈ΋ ‰È¿ÁÓˆÛË ÂÈÛÊÚ·Á›˙ÂÙ·È ·fi ÙËÓ ÈÛÙÔ·ıÔÏÔÁÈ΋ ÌÂϤÙË. ∂ÓÙÔ‡ÙÔȘ, Ë ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÌÔÚ› Ó· ηı›ÛÙ·Ù·È ‰‡ÛÎÔÏË, ÏfiÁˆ Ù˘ ÛÙÂÓ‹˜ ÔÌÔÈfiÙËÙ·˜ Û ÂÚÈÙÒÛÂȘ ÏÈÔÛ·ÚÎÒÌ·ÙÔ˜. ∆· ÏÈÔÛ·ÚÎÒÌ·Ù· ÌÔÚ› Ó· ÂÚȤ¯Ô˘Ó ¿Ù˘Ô˘˜ ÌÈÙˆÙÈÎÔ‡˜ Û¯ËÌ·ÙÈÛÌÔ‡˜ Î·È ¿Ù˘Ô˘˜ ‹ ˘Âگڈ̷ÙÈÎÔ‡˜ ˘Ú‹Ó˜, ÔÈ ÔÔ›ÔÈ ‰ÂÓ ·Ó¢ڛÛÎÔÓÙ·È ÛÙ· ÏÈÔ‚Ï·ÛÙÒÌ·Ù· (1). øÛÙfiÛÔ, Ë ÈÛÙÔÏÔÁÈ΋ ÂÈÎfiÓ· ÂÓfi˜ ηϿ ‰È·ÊÔÚÔÔÈË̤ÓÔ˘ ‚ÏÂÓÓÒ‰Ô˘˜ ÏÈÔÛ·ÚÎÒÌ·ÙÔ˜ ·ÚÔ˘ÛÈ¿˙ÂÈ Ì›· ÂÓÙ˘ˆÛȷ΋ ÔÌÔÈfiÙËÙ· Ì ÙÔ ÏÈÔ‚Ï¿Ûو̷ Î·È ÌÔÚ› Ó· Â›Ó·È ‰˘Û‰È¿ÎÚÈÙË ·fi ·˘Ùfi (1). ∏ ÂͤٷÛË ÙÔ˘ ηڢÔÙ‡Ô˘ ÌÔÚ› Ó· ·Ԃ› ¯Ú‹ÛÈÌË ÛÙË ‰È·ÊÔÚԉȿÁÓˆÛË ·˘ÙÒÓ ÙˆÓ ÏÈˆ‰ÒÓ fiÁÎˆÓ (8). ™Â ÔÏϤ˜ ÂÚÈÙÒÛÂȘ, Ë ËÏÈΛ· ÙÔ˘ ·ÛıÂÓ‹ ηı›ÛÙ·Ù·È ÛËÌ·ÓÙÈ΋ ‚Ô‹ıÂÈ· ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ fiÁÎÔ˘ (8). ∆Ô ÏÈÔ‚Ï¿Ûو̷ ÂÌÊ·Ó›˙ÂÙ·È Û¯Â‰fiÓ ·ÔÎÏÂÈÛÙÈο ÛÙ· Ó‹È· Î·È Ù· ÌÈÎÚ¿ ·È‰È¿ (Û·Ó›ˆ˜ ÌÂÙ¿ ÙËÓ ËÏÈΛ· ÙˆÓ 10 ÂÙÒÓ), ÂÓÒ ÙÔ ÏÈÔÛ¿ÚΈ̷ Â›Ó·È ÂÍ·ÈÚÂÙÈο Û¿ÓÈÔ Û ·ÛıÂÓ›˜ ËÏÈΛ·˜ ÌÈÎÚfiÙÂÚ˘ ÙˆÓ 10 ÂÙÒÓ. √È Mentzel Î·È Û˘Ó ÂÚÈÁÚ¿ÊÔ˘Ó ÌfiÓÔ 4 ÂÚÈÙÒÛÂȘ ηϿ ÂÚÈÁÂÁÚ·ÌÌ¤ÓˆÓ ÏÈÔÛ·ÚÎˆÌ¿ÙˆÓ Û ·È‰È¿ ËÏÈΛ·˜ ÌÈÎÚfiÙÂÚ˘ ÙˆÓ 10 ÂÙÒÓ (9). ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ÂÚÈÁÚ¿„ÂÈ Û˘ÁÎÂÎÚÈ̤Ó˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜, ÔÈ Ôԛ˜ ¯·Ú·ÎÙËÚ›˙Ô˘Ó ÙÔ˘˜ ηÏÔ‹ıÂȘ Î·È Î·ÎÔ‹ıÂȘ fiÁÎÔ˘˜ ÙÔ˘ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ Î·È Â›Ó·È ÌÂÁ¿Ï˘ ‰È·ÁÓˆÛÙÈ΋˜ Î·È ÎÏÈÓÈ΋˜ ÛËÌ·Û›·˜. ¶·È‰È·ÙÚÈ΋ 2006;69:313-316

316

Õ. ∆Û·ÏΛ‰Ë˜ Î·È Û˘Ó.

∆Ô 1986, ÔÈ Sandberg Î·È Û˘Ó ÂÚȤÁÚ·„·Ó ÏÈÔ‚Ï¿Ûو̷ Û ·ÁfiÚÈ ËÏÈΛ·˜ 2 ÂÙÒÓ, Ô˘ ÂÌÊ¿ÓÈ˙ ÌÂÙ¿ıÂÛË ÌÂٷ͇ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ 7 Î·È 8 (10). ŒÎÙÔÙÂ, ¤¯Ô˘Ó ·Ó·ÊÂÚı› ·ÚÎÂÙ¤˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Ì ÎÔÈÓfi ¯·Ú·ÎÙËÚÈÛÙÈÎfi ÙË Û˘ÌÌÂÙÔ¯‹ ÛÙȘ ·ÓˆÌ·Ï›Â˜ ·˘Ù¤˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 8 (ÂÚÈÔ¯‹ 8q11-q13) ÛÙÔ ÏÈÔ‚Ï¿Ûو̷ Î·È ÛÙË ÏÈÔ‚Ï·Ûو̿وÛË (11) Î·È ÙË ÌÂÙ¿ıÂÛË t(2;16)(q13;p11) ÛÙÔ ‚ÏÂÓÓ҉˜ ÏÈÔÛ¿ÚΈ̷ (1). ∏ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋ ÂͤٷÛË ÙˆÓ fiÁÎˆÓ ·Ú¤¯ÂÈ ÚfiÛıÂÙ˜ ¯Ú‹ÛÈ̘ ÏËÚÔÊÔڛ˜, Û˘Ì‚¿ÏÏÔÓÙ·˜ ÛÙËÓ Î·ÙËÁÔÚÈÔÔ›ËÛË ÙˆÓ ÏÈˆ‰ÒÓ fiÁÎˆÓ Î·È ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜ ·fi ÙÔ ÏÈÔÛ¿ÚΈ̷. ™‡Ìʈӷ Ì ÙÔ˘˜ Miller Î·È Û˘Ó Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÙ·È ˘ÏÈÎfi ·fi fiÏÔ˘˜ ÙÔ˘˜ ·Û˘Ó‹ıÂȘ ·È‰È·ÙÚÈÎÔ‡˜ fiÁÎÔ˘˜ ÙÔ˘ ÏÈÒ‰Ô˘˜ ÈÛÙÔ‡ (ÌË ÂÚÈÁÂÁÚ·Ì̤ÓÔÈ Û·ÊÒ˜) Î·È Ó· ÂÍÂÙ¿˙ÂÙ·È ÈÛÙÔÏÔÁÈο Î·È ÌÔÚȷο (8). ∏ ·ÎÚÈ‚‹˜ ‰È¿ÁÓˆÛË Â›Ó·È Ô˘ÛÈ·ÛÙÈ΋˜ ÛËÌ·Û›·˜ ÁÈ· ÙËÓ ÂÚ·ÈÙ¤Úˆ ıÂÚ·¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË (1). ∆Ô ÏÈÔ‚Ï¿Ûو̷ ÙÔ˘ ÙÚ·¯‹ÏÔ˘ Â›Ó·È fiÁÎÔ˜ Ô˘ ·˘Í¿ÓÂÙ·È ÁÚ‹ÁÔÚ· (2), ·ÏÏ¿ ÛÙËÓ ÂͤÏÈÍ‹ ÙÔ˘ - Û˘Ó‹ıˆ˜ - ‰ÂÓ ‰ËÌÈÔ˘ÚÁ› Û˘ÌÙÒÌ·Ù· ·fi ÙȘ ·Ú·Î›ÌÂÓ˜ ·Ó·ÙÔÌÈΤ˜ ÂÚÈÔ¯¤˜, fiˆ˜ Û˘Ó¤‚Ë Î·È ÛÙËÓ ·ÚÔ‡Û· ÂÚ›ÙˆÛË. ¶·Ú’ fiÏ· ·˘Ù¿, ÂÚÈÁÚ¿ÊÔÓÙ·È ‰‡Ô ÂÚÈÙÒÛÂȘ ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜ ÙÚ·¯‹ÏÔ˘, fiÔ˘ ·Ó·Ê¤ÚÂÙ·È ‰È·Ï›Ô˘Û· ·ÓÂ¿ÚÎÂÈ· ·Ó·Ó¢ÛÙÈÎÒÓ Ô‰ÒÓ (2,12) Î·È Ì›· ÂÚ›ÙˆÛË ËÌÈ¿ÚÂÛ˘, ÔÊÂÈÏfiÌÂÓË Û ÏÈÔ‚Ï·Ûو̿وÛË (12). ¢ÂÓ ·Ó·Ê¤ÚÔÓÙ·È ÂÚÈÙÒÛÂȘ Ì ÂͤÏÈÍË Û ηÎfiËı˜ ÓÂfiÏ·ÛÌ· (13). ™Â ·ÚÎÂÙ¤˜ ÂÚÈÙÒÛÂȘ, Ë ·Ó¿Ù˘ÍË ÙÔ˘ ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜ Â›Ó·È ‰˘Ó·Ùfi Ó· Ï¿‚ÂÈ ÙÂÚ¿ÛÙȘ ‰È·ÛÙ¿ÛÂȘ Î·È ÁÈ· ÙÔÓ ÏfiÁÔ ·˘Ùfi Ë ÔÏÈ΋ ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË ÙÔ˘ fiÁÎÔ˘ Â›Ó·È Ë Ì¤ıÔ‰Ô˜ ÂÎÏÔÁ‹˜ (13). øÛÙfiÛÔ, ˘¿Ú¯ÂÈ ·Ó·ÊÔÚ¿ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· fiÔ˘ ÂÚÈÁÚ¿ÊÂÙ·È ·˘ÙfiÌ·ÙË ˘Ô¯ÒÚËÛË Ù˘ ‚Ï¿‚˘ (13). ∏ Â·ÓÂÌÊ¿ÓÈÛË ÙÔ˘ fiÁÎÔ˘ ÌÂÙ¿ ÙËÓ ÂÍ·›ÚÂÛ‹ ÙÔ˘ Â›Ó·È Û¿ÓÈ· ÛÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ ÏÈÔ‚Ï·ÛÙÒÌ·ÙÔ˜ Î·È ÂÍ·ÚÙ¿Ù·È ·fi ÙÔÓ ÂÓÙÔÈÛÌfi Î·È ÙÔÓ ‚·ıÌfi ‰È‹ıËÛ˘ ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙ· ÈÛÙÔ‡, ÂÓÒ ÛÙË ÏÈÔ‚Ï·Ûو̿وÛË ÌÔÚ› Ó· Û˘Ì‚Â› Û ÔÛÔÛÙfi 10-25% Î·È Ó· ··ÈÙËıÔ‡Ó ÂÚÈÛÛfiÙÂÚ˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ (1-4). ¶ÚÔ‚Ï‹Ì·Ù· Â›Ó·È ‰˘Ó·Ùfi Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó Û ÏÈÔ‚Ï¿Ûو̷ ÂÓ Ùˆ ‚¿ıÂÈ ÂÓÙfiÈÛ˘ Î·È Û ‰È¿¯˘ÙË ÏÈÔ‚Ï·Ûو̿وÛË, fiÙ·Ó Ô fiÁÎÔ˜ ‰ÂÓ ÌÔÚ› Ó· ·Ê·ÈÚÂı› Ï‹Úˆ˜ ¯ˆÚ›˜ ηٷÛÙÚÔÊ‹ ÙˆÓ ÛËÌ·ÓÙÈÎÒÓ ·Ú·Î›ÌÂÓˆÓ ÈÛÙÒÓ, fiˆ˜ fiÙ·Ó ·Ó·Ù‡ÛÛÂÙ·È ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÓˆÙÈ·›Ô˘ ۈϋӷ ‹ ÂÚÈÔÚıÈο. ¶·È‰È·ÙÚÈ΋ 2006;69:313-316

™˘ÌÂÚ·ÛÌ·ÙÈο, ÙÔ ÏÈÔ‚Ï¿Ûو̷ ·ÔÙÂÏ› ¤Ó· Û¿ÓÈÔ ·›ÙÈÔ ‰ÈfiÁΈÛ˘ ÛÙËÓ ÙÚ·¯ËÏÈ΋ ¯ÒÚ·, Ô˘ Ú¤ÂÈ fï˜ Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË. √ ˘„ËÏfi˜ ‚·ıÌfi˜ ˘Ô„›·˜ ÂÈÙÚ¤ÂÈ ÙÔÓ ¿ÌÂÛÔ Î·ıÔÚÈÛÌfi Ù˘ ʇÛ˘ Ù˘ ‰ÈfiÁΈÛ˘, ¤ÙÛÈ ÒÛÙÂ Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË Ó· Ú·ÁÌ·ÙÔÔÈËı› Û ÚÒÈÌÔ ÛÙ¿‰ÈÔ, ‰ËÏ·‰‹ ÚÈÓ ÙÔ ÏÈÔ‚¿Ûو̷ ·˘ÍËı› Û ‰È·ÛÙ¿ÛÂȘ, ÁÂÁÔÓfi˜ Ô˘ Â›Ó·È Èı·Ófi Ó· ηٷÛÙ‹ÛÂÈ ÙËÓ ÂÍ·›ÚÂÛ‹ ÙÔ˘ ‰˘Û¯ÂÚ‹, ·˘Í¿ÓÔÓÙ·˜ ÙȘ Èı·ÓfiÙËÙ˜ ˘ÔÙÚÔ‹˜.

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9. Mentzel T, Calonje E, Fletcher CD. Lipoblastoma and lipoblastomatosis: a clinicopathological study of 14 cases. Histopathology 1993;23:527-533.

10. Sandberg AA, Gibas Z, Saren E, Li FP, Limon J, Tebbi CK. Chromosome abnormalities in two benign adipose tumors. Cancer Genet Cytogenet 1986;22:55-61.

11. Fletcher CD, Akerman M, Dal Cin P, de Wever I, Mandahl N, Mertens F et al Correlation between clinicopathological features and karyotype in lipomatous tumors. A report of 178 cases from the Chromosomes and Morphology (CHAMP) Collaborative Study Group. Am J Pathol 1996;148:623-630.

12. Sun JJ, Rasgon BM, Hilsinger RL Jr. Lipoblastomatosis of the neck causing hemiparesis: a case report and review of the literature. Head Neck 2003;25:337-340.

13. Mognato G, Cecchetto G, Carli M, Talenti E, d’Amore ES, Pederzini F et al. Is surgical treatment of lipoblastoma always necessary? J Pediatr Surg 2000; 35:1511-1513.

¶ƒ∞∫∆π∫√ £∂ª∞

PRACTICAL ISSUE

317

¡ÙfiÈÓÁÎ Û ·È‰È¿, ÂÊ‹‚Ô˘˜ Î·È Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ ™. ∞ÓÙˆÓÈ¿‰Ë˜

¶ÂÚ›ÏË„Ë: ∆Ô ÓÙfiÈÓÁÎ ·ÔÙÂÏ› ¤Ó· ·fi Ù· ÚÔ‚Ï‹Ì·Ù· ‰ËÌfiÛÈ·˜ ˘Á›·˜, ÙÔ ÔÔ›Ô - Û ·ÓÙ›ıÂÛË Ì ¿ÏÏ·, fiˆ˜ .¯. ÙÔ Î¿ÓÈÛÌ·, Ù· Ó·ÚΈÙÈο Î.¿. - ¿ÚÁËÛ ӷ Á›ÓÂÈ ·ÓÙÈÏËÙfi. ∏ ¯Ú‹ÛË ‰È·ÊfiÚˆÓ Ô˘ÛÈÒÓ ÁÈ· ÙËÓ ·‡ÍËÛË Ù˘ ‰‡Ó·Ì˘, ÙËÓ ÂÓ›Û¯˘ÛË Ù˘ ·ÓÙÔ¯‹˜, ÙË ÌÂÁ·Ï‡ÙÂÚË ·ÓÔ¯‹ ÛÙÔÓ fiÓÔ Î.Ï. Â›Ó·È ÁÓˆÛÙ‹ ·fi ÙËÓ ·Ú¯·ÈfiÙËÙ·. ™ÙȘ ̤Ú˜ Ì·˜, fiˆ˜ Ê·›ÓÂÙ·È, ÙÔ ÓÙfiÈÓÁÎ ·ÔÙÂÏ› Û˘Ó‹ıË Ú·ÎÙÈ΋ ÛÙÔÓ “Âϛٔ ÚˆÙ·ıÏËÙÈÛÌfi, ÛÙÔÓ ¤ÓÙÔÓÔ ·ıÏËÙÈÛÌfi Î·È Û ·˘ÙÔ‡˜ Ô˘ ·Û¯ÔÏÔ‡ÓÙ·È Ì ÙË ÛˆÌ·ÙÔ‰fiÌËÛË (body-building). ™ÙȘ ÎÔÈӈӛ˜ ÙˆÓ ÓÈÎËÙÒÓ Î·È ËÙÙË̤ӈÓ, fiÔ˘ Ë ‰È¿ÎÚÈÛË Û ¤Ó· ¿ıÏËÌ· ÛËÌ·›ÓÂÈ ¯Ú‹Ì·, ‰fiÍ·, ·ÏÏ¿ Î·È ÔÈΛϷ ¿ÏÏ· ÔʤÏË (.¯. ÂÈÛ·ÁˆÁ‹ ÛÙËÓ ÙÚÈÙÔ‚¿ıÌÈ· ÂÎ·›‰Â˘ÛË), Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ·ÓÙÈÛÙ·ıÔ‡Ó ÔÈ Ó¤ÔÈ Î·È Ó· ·ÚÎÂÛÙÔ‡Ó ÌfiÓÔ ÛÙȘ ‰˘Ó¿ÌÂȘ Ô˘ ÙÔ˘˜ ·Ú¤¯ÂÈ ÙÔ ÛÒÌ· ÙÔ˘˜. √È Ô˘Û›Â˜ Î·È ÔÈ Ì¤ıÔ‰ÔÈ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Â›Ó·È ÔÏϤ˜ Î·È ÔÈΛϘ, ¿ÏϘ ÁÓˆÛÙ¤˜ ·fi ÙÔ ·ÚÂÏıfiÓ Î·È ¿ÏϘ ·ÔÙÂÏÔ‡Ó ÚfiÛÊ·Ù· ÂÈÙ‡ÁÌ·Ù· Ù˘ ÂÈÛÙ‹Ì˘. √È ÂÈÙÒÛÂȘ ÂÍ·ÚÙÒÓÙ·È ·fi ÙË Û˘ÁÎÂÎÚÈ̤ÓË Ô˘Û›·, ÙË ‰fiÛË, ·ÏÏ¿ Î·È ÙÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÁÈ· ÙÔ ÔÔ›Ô ¯ÚËÛÈÌÔÔÈ›ٷÈ. ªÂٷ͇ ÙˆÓ ‰È·ÊfiÚˆÓ ÚÔ‚ÏËÌ¿ÙˆÓ ˘Á›·˜ Ô˘ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È, ΢ڛ·Ú¯Ô ÚfiÏÔ ¤¯Ô˘Ó Ù· ηډÈÔÏÔÁÈο, ·fi Ù· ÔÔ›· Î·È ÚÔηÏÂ›Ù·È Ô ÌÂÁ·Ï‡ÙÂÚÔ˜ ·ÚÈıÌfi˜ ÙˆÓ ı·Ó¿ÙˆÓ. øÛÙfiÛÔ, ˘¿Ú¯ÂÈ ¤ÏÂÁ¯Ô˜ ·ÓÙÈ-ÓÙfiÈÓÁÎ, ηıÒ˜ ‰È¿ÊÔÚ˜ ÂıÓÈΤ˜ Î·È ‰ÈÂıÓ›˜ ÂÈÙÚÔ¤˜ Ï·Ì‚¿ÓÔ˘Ó Ì¤ÙÚ· ÁÈ· ÙËÓ Î·Ù·ÔϤÌËÛË Ù˘ ¯Ú‹Û˘ ··ÁÔÚÂ˘Ì¤ÓˆÓ Ô˘ÛÈÒÓ ÛÙÔÓ ·ıÏËÙÈÛÌfi. ™Â fi,ÙÈ ·ÊÔÚ¿ Ù· ·È‰È¿, ÙÔ Úfi‚ÏËÌ· ‰ÂÓ Ê·›ÓÂÙ·È Ó· ·ÁÁ›˙ÂÈ ÙȘ Ôχ ÌÈÎÚ¤˜ ËÏÈ˘. ∞ÓÙ›ıÂÙ·, ÛÙÔ˘˜ ÂÊ‹‚Ô˘˜ Î·È ÛÙÔ˘˜ Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ ı· Ú¤ÂÈ Ó· ‰›ÓÂÙ·È È‰È·›ÙÂÚË ÚÔÛÔ¯‹. ∏ Â¤Ì‚·ÛË ÙˆÓ ·È‰È¿ÙÚˆÓ Û›ÁÔ˘Ú· ı· Û˘Ì‚¿ÏÂÈ ıÂÙÈο ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ÓÙfiÈÓÁÎ, ÂÍ Ô˘ Î·È Ë ÛËÌ·Û›· ÙÔ˘ ·ÚfiÓÙÔ˜ ¿ÚıÚÔ˘.

¶·È‰ÔηډÈÔÏfiÁÔ˜, ∫·ıËÁËÙ‹˜ ∞ÓÒÙ·ÙÔ˘ ∆¯ÓÔÏÔÁÈÎÔ‡ ∂Î·È‰Â˘ÙÈÎÔ‡ π‰Ú‡Ì·ÙÔ˜ ∞ıËÓÒÓ AÏÏËÏÔÁÚ·Ê›·: ™Ù˘ÏÈ·Ófi˜ ∞ÓÙˆÓÈ¿‰Ë˜ ∏Ú·ÎÏ›ÙÔ˘ 4 ∆.∫. 106 73, ∫ÔψӿÎÈ E-mail: prdrsant@otenet.gr ∏ÌÂÚÔÌËÓ›· ˘Ô‚ÔÏ‹˜: 24-11-2005 ∏ÌÂÚÔÌËÓ›· ¤ÁÎÚÈÛ˘: 28-03-2006

§¤ÍÂȘ ÎÏÂȉȿ: ¡ÙfiÈÓÁÎ, ·ÓÙÈ-ÓÙfiÈÓÁÎ, ·È‰È¿, ¤ÊË‚ÔÈ, Ó·ÚÔ› ÂÓ‹ÏÈΘ.

Doping in children, adolescents and young adults S. Antoniadis

Abstract: Doping is a public health problem which in contrast with others, such as smoking and drug abuse, was realized with some delay. The use of various performance enhancing substances to increase strength, endurance and tolerance to pain, has been observed since ancient times. Today doping appears to be a common practice among elite athletes, those playing sports at competition level and bodybuilders. In winner-loser societies, where distinction in sports means money, glory and other benefits such as entrance to higher education, it is very difficult for a young person to be convinced that his/her natural physical strength is enough. There is a long list of performance enhancing substances and methods some of which have been known for many years and others that represent recent scientific advances. The potential harmful effects depend on what is used and on the dosage and the length of the time of use. Among the various health problems that the athletes may develop, those involving the heart are more frequently related to death. For the prevention of doping there are national and international committees for anti-doping and lists of prohibited substances and methods. As far as children are concerned, doping does not appear to be a problem in the very young age group, but care needs to be taken for teenagers and young adults. The role of the paediatrician can obviously play a very significant role in the control of doping, which is the importance of this article.

Paediatric Cardiologist, Professor of the Highest Technological Educational Institution of Athens Correspondence: Stilianos Antoniadis 4, Iraklitou Str. 106 73, Kolonaki Date of submission: 24-11-2005 Date of approval: 28-03-2006

Key words: Doping, anti-doping, children, adolescents, young adults.

¶·È‰È·ÙÚÈ΋ 2006;69:317-322

318

™. ∞ÓÙˆÓÈ¿‰Ë˜

∂ÈÛ·ÁˆÁ‹ ∏ ¯Ú‹ÛË Ê·Ú̷΢ÙÈÎÒÓ ‹ ¿ÏÏˆÓ Ô˘ÛÈÒÓ Ô˘ ‚ÔËıÔ‡Ó ÛÙËÓ ·‡ÍËÛË Ù˘ ·fi‰ÔÛ˘ ηıÒ˜ Î·È ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ Â͈ÙÂÚÈ΋˜ ÂÌÊ¿ÓÈÛ˘ Â›Ó·È ÁÓˆÛÙ‹ Â‰Ò Î·È ÔÏϤ˜ ÂηÙÔÓÙ¿‰Â˜ ¯ÚfiÓÈ· (1-3). ™ÙȘ ̤Ú˜ Ì·˜, Ì ÙËÓ ÂÌÔÚÂ˘Ì·ÙÔÔ›ËÛË ÙÔ˘ ·ıÏËÙÈÛÌÔ‡, fiÔ˘ Ë Ó›ÎË ÛËÌ·›ÓÂÈ ¯Ú‹Ì· Î·È ‰fiÍ·, Ê·›ÓÂÙ·È fiÙÈ Ë ·Ó·˙‹ÙËÛË ıÂÌÈÙÒÓ ‹ ·ı¤ÌÈÙˆÓ ÌÂıfi‰ˆÓ Ô˘ ÌÔÚ› Ó· ʤÚÔ˘Ó ÙË ‰È¿ÎÚÈÛË, ·ÔÙÂÏ› ÚÔÛÊÈÏ‹ Û˘Ó‹ıÂÈ· ÌÂٷ͇ ÙˆÓ ·ıÏËÙÒÓ ‹ ÙˆÓ Â›‰ÔÍˆÓ ÚˆÙ·ıÏËÙÒÓ (4-6). °È· ÙËÓ ÂÈÙ˘¯‹ ·ÓÙÈÌÂÙÒÈÛË ‹ ÙÔÓ ÂÚÈÔÚÈÛÌfi ÙÔ˘ ÓÙfiÈÓÁÎ, ÙÔ ÔÔ›Ô ϤÔÓ ¤¯ÂÈ Ï¿‚ÂÈ ‰È·ÛÙ¿ÛÂȘ ÚÔ‚Ï‹Ì·ÙÔ˜ ‰ËÌfiÛÈ·˜ ˘Á›·˜ (7), Â›Ó·È ··Ú·›ÙËÙË Ë ÂÓË̤ڈÛË Î·È ÁÂÓÈÎfiÙÂÚ· Ë ‰È‡ڢÓÛË ÙˆÓ ÁÓÒÛÂˆÓ Û¯ÂÙÈο Ì ·˘Ùfi ÙÔ ı¤Ì· fiÏˆÓ ÙˆÓ ÊÔÚ¤ˆÓ Ô˘ ·Û¯ÔÏÔ‡ÓÙ·È Ì ÙÔÓ ·ıÏËÙÈÛÌfi (8). π‰È·›ÙÂÚË ÛËÌ·Û›· ¤¯ÂÈ Ë ÂÓË̤ڈÛË ÙˆÓ ÁÈ·ÙÚÒÓ, ‰ÈfiÙÈ ·fi fi,ÙÈ Ê·›ÓÂÙ·È ·fi ÙË ‚È‚ÏÈÔÁÚ·Ê›·, ÙÔ ÓÙfiÈÓÁÎ Á›ÓÂÙ·È ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ Ì ÙË Û˘Ì‚ÔÏ‹ ÙˆÓ ÁÈ·ÙÚÒÓ (Î·È ÙˆÓ Ê·ÚÌ·ÎÔÔÈÒÓ). §·Ì‚¿ÓÔÓÙ·˜, ÏÔÈfiÓ, ˘’ fi„ÈÓ ÙÔ Ì¤ÁÂıÔ˜ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜, ·ÏÏ¿ Î·È ıˆÚÒÓÙ·˜ fiÙÈ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚË ·ÓÙÈÌÂÙÒÈÛË ÂÍ·ÚÙ¿Ù·È ·fi ÙÔÓ ‚·ıÌfi ÂÓË̤ڈÛ˘-ÂÎ·›‰Â˘Û˘, ΢ڛˆ˜ ÙˆÓ ÁÈ·ÙÚÒÓ, Á›ÓÂÙ·È Â‡ÎÔÏ· ·ÓÙÈÏËÙfi fiÛÔ Â›Î·ÈÚË Â›Ó·È ·˘Ù‹ Ë ·Ó·ÛÎfiËÛË (9).

πÛÙÔÚ›· ÙÔ˘ ÓÙfiÈÓÁÎ ∆Ô ÓÙfiÈÓÁÎ Â›Ó·È Û˘Ó‰Â‰Â̤ÓÔ Ì ÙËÓ ÈÛÙÔÚ›· ÙÔ˘ ·ıÏËÙÈÛÌÔ‡. À¿Ú¯Ô˘Ó ΛÌÂÓ· ÙÔ˘ ¶˘ı·ÁfiÚ·, ÙÔ˘ πÔÎÚ¿ÙË Î·È ÙÔ˘ ∞ÚÈÛÙÔÙ¤ÏË Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙË ¯Ú‹ÛË ‰È·ÊfiÚˆÓ Ô˘ÛÈÒÓ/‚ÔËıËÌ¿ÙˆÓ ÁÈ· ÙËÓ ·‡ÍËÛË Ù˘ ·fi‰ÔÛ˘. ™ÙË ÚˆÌ·˚΋ ÂÔ¯‹, Â›Û˘, ˘¿Ú¯Ô˘Ó ÔÏÏ·Ϥ˜ ·Ó·ÊÔÚ¤˜ ·fi ÙÔÓ ºÈÏfiÛÙÚ·ÙÔ, ÙÔÓ æ¢‰ÔÁ·ÏËÓfi, ÙÔÓ √ÚÂÈ‚¿ÛÈÔ Î.Ï. ∂›Ó·È ‰Â, ÁÓˆÛÙ‹ Ë ÂÚ›ÙˆÛË ÓÙfiÈÓÁÎ ÛÙËÓ ÚÒÙË √Ï˘ÌÈ¿‰· (10).

∆Ô ÓÙfiÈÓÁÎ Û‹ÌÂÚ· ™ÙȘ ̤Ú˜ Ì·˜, ÙÔ ÓÙfiÈÓÁÎ ·ÊÔÚ¿ ΢ڛˆ˜ ÛÙÔ˘˜ ÚˆÙ·ıÏËÙ¤˜ Î·È È‰È·›ÙÂÚ· ÛÙËÓ “Âϛٔ ÙˆÓ ÚˆÙ·ıÏËÙÒÓ, ηıÒ˜ Î·È Û fiÛÔ˘˜ ·Û¯ÔÏÔ‡ÓÙ·È Ì ÙË ÛˆÌ·ÙÔ‰fiÌËÛË (body-building). øÛÙfiÛÔ, fiˆ˜ ı· Ê·Ó› ÛÙË Û˘Ó¤¯ÂÈ·, ·ÔÙÂÏ› ¤Ó· ¢ڇÙÂÚÔ ÎÔÈÓˆÓÈÎfi Úfi‚ÏËÌ·. ¶·È‰È·ÙÚÈ΋ 2006;69:317-322

√˘Û›Â˜ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙÔ ÓÙfiÈÓÁÎ °ÂÓÈο, Ù· Ê¿Ú̷η Î·È ÔÈ Ì¤ıÔ‰ÔÈ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û‹ÌÂÚ·, ·ÏÏ¿ Î·È Ù· ¿ÏÏ· ̤۷ Ô˘ Èı·ÓÒ˜ ı· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÛÙÔ Ì¤ÏÏÔÓ (11), ·ÔÙÂÏÔ‡Ó ÚfiÎÏËÛË ÁÈ· ÙÔ˘˜ ÂÈÛÙ‹ÌÔÓ˜. ∞ӷʤÚÔÓÙ·È Û˘ÓÔÙÈο ÛÙË Û˘Ó¤¯ÂÈ· ÔÈ Î˘ÚÈfiÙÂÚ˜ ηÙËÁÔڛ˜: ·) ¢ÈÂÁÂÚÙÈο: ηʽÓË, ÎÔη˝ÓË, ·ÌÊÂٷ̛Ә, ÂʉڛÓË, ÊÂÓÊÏÔ˘Ú·Ì›ÓË Î.Ï. ∞˘Í¿ÓÔ˘Ó ÙËÓ ·ÓÙÔ¯‹, ‰ËÌÈÔ˘ÚÁÔ‡Ó ·›ÛıËÌ· ·˘ÙÔÂÔ›ıËÛ˘ Î·È ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ·˘ÙÔÛ˘ÁΤÓÙÚˆÛË. ™ÙȘ ·ÚÂÓ¤ÚÁÂȘ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È: ‰È¤ÁÂÚÛË, ÙÚfiÌÔ˜, ·ÚÚ˘ı̛˜, ˘¤ÚÙ·ÛË Î.Ï. ™Â ·Ú·ÙÂٷ̤ÓË Î·È ˘ÂÚ‚ÔÏÈ΋ ¯Ú‹ÛË ÌÔÚ› Ó· ·Ú·ÙËÚËı› ·ÎfiÌË Î·È ı¿Ó·ÙÔ˜. ‚) ∞Ó·‚ÔÏÈο ÛÙÂÚÔÂȉ‹: ÙÂÛÙÔÛÙÂÚfiÓË, ‰È¸‰ÚÔÙÂÛÙÔÛÙÂÚfiÓË, ‰È¸‰ÚÔÂÈ·Ó‰ÚÔÛÙÂÚfiÓË, ÎÏÂÓ‚Ô˘ÙÂÚfiÏË Î.Ï. ¶ÚÔηÏÔ‡Ó ·‡ÍËÛË Ù˘ Ì˘˚΋˜ ‰‡Ó·Ì˘ Î·È Ù˘ Ì˘˚΋˜ Ì¿˙·˜. ™ÙȘ ·ÚÂÓ¤ÚÁÂȘ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ·ÏÏ·Á¤˜ ÛÙ· Â͈ÙÂÚÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ʇÏÔ˘. ™ÙȘ Á˘Ó·›Î˜ ÚÔηÏÂ›Ù·È ÌÈÎÚfi ̤ÁÂıÔ˜ Ì·ÛÙÒÓ, ‰È·Ù·Ú·¯¤˜ Ù˘ ÂÌÌËÓÔÚÚ˘Û›·˜ Î·È Ù˘ ʈӋ˜. ™ÙÔ˘˜ ¿ÓÙÚ˜ ·Ú·ÙËÚÂ›Ù·È Á˘Ó·ÈÎÔÌ·ÛÙ›· (12), ·ÙÚÔÊ›· ÙˆÓ fiÚ¯ÂˆÓ Î·È ·ÒÏÂÈ· ÙÚȯÒÓ Ù˘ ÎÂÊ·Ï‹˜ (13-16). ∂›Û˘, ÌÔÚ› Ó· ÚÔÎÏËıÔ‡Ó ˘¤ÚÙ·ÛË, ‰ÂÚÌ·Ù›Ùȉ˜ (17), ÚÔ‚Ï‹Ì·Ù· ‹·ÙÔ˜ (18) Î·È ÓÂÊÚÒÓ, ‰È·Ù·Ú·¯¤˜ ÚÔÛˆÈÎfiÙËÙ·˜, ÂÈıÂÙÈ΋ Û˘ÌÂÚÈÊÔÚ¿ Î.¿. (19-22). ™Ô‚·Úfiٷ٘ ·ÚÂÓ¤ÚÁÂȘ ·ÔÙÂÏÔ‡Ó Ë ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ˜ (23,24) Î·È Ë ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· ·Ó¿Ù˘Í˘ ηÎÔ‹ıˆÓ ÂÍÂÚÁ·ÛÈÒÓ (25,26). Á) ‚-∞Ó·ÛÙÔÏ›˜: ÚÔÚ·ÓÔÏfiÏË, ÛÔÙ·ÏfiÏË, ·ÎÂÙÔ‚Ô˘Ù˘ÏfiÏË Î.¿. ¶ÚÔηÏÔ‡Ó ‚Ú·‰˘Î·Ú‰›·, ÂÏ¿ÙÙˆÛË ÙÔ˘ Ì˘˚ÎÔ‡ ÙÚfiÌÔ˘ Î.Ï. ™Â ÌÈÎÚ¤˜ ‰fiÛÂȘ ‰ÂÓ ÚÔηÏÔ‡Ó È‰È·›ÙÂÚ· ÚÔ‚Ï‹Ì·Ù·. øÛÙfiÛÔ, Û ·Ú·ÙÂٷ̤ÓË ¯Ú‹ÛË Î·È ÌÂÁ¿Ï˜ ‰fiÛÂȘ ˘¿Ú¯ÂÈ Èı·ÓfiÙËÙ· ÂÁÎÂÊ·ÏÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ (27). ‰) ¢ÈÔ˘ÚËÙÈο: ÊÔ˘ÚÔÛÂÌ›‰Ë, ÛÈÚÔÓÔÏ·ÎÙfiÓË, ˘‰ÚԯψÚÔıÂÈ·˙›‰Ë Î.Ï. ÃÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· ·ÒÏÂÈ· ‚¿ÚÔ˘˜ (΢ڛˆ˜ ÛÙËÓ ¿ÚÛË ‚·ÚÒÓ, ÙËÓ ¿ÏË Î.¿.), ·ÏÏ¿ Î·È ÁÈ· ·Ô‚ÔÏ‹ ‹ ·Ú·›ˆÛË ‰È·ÊfiÚˆÓ Ô˘ÛÈÒÓ ÛÙÔ ·›Ì·. ™Â ·ÏfiÁÈÛÙË ¯Ú‹ÛË ÌÔÚ› Ó· ÚÔηϤÛÔ˘Ó ·Ê˘‰¿ÙˆÛË, Ì˘˚Τ˜ ‰È·Ù·Ú·¯¤˜, ηıÒ˜ Î·È ‰È·Ù·Ú·¯¤˜ ·fi ÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ· (27). Â) ¡·ÚΈÙÈο ·Ó·ÏÁËÙÈο: ÌÔÚÊ›ÓË, Âıȉ›ÓË, ÌÂı·‰fiÓË, Έ‰Â˝ÓË, ÔÈÔ‡¯· Î.Ï. ÃÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· ÙË Ì›ˆÛË ÙÔ˘ ¿ÏÁÔ˘˜ (΢ڛˆ˜ ˘ÁÌ·¯›·). ¶ÚÔηÏÔ‡Ó ÂıÈÛÌfi, ·ÏÏ¿ ηÈ

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¡ÙfiÈÓÁÎ Û ·È‰È¿, ÂÊ‹‚Ô˘˜ Î·È Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ

·ÚÚ˘ı̛˜, ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ηډȷÁÁÂÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ÂÁÎÂÊ·ÏÈ΋ ·ÈÌÔÚÚ·Á›· Î.¿. ÛÙ) ¶ÂÙȉÈΤ˜ ÔÚÌfiÓ˜: ACTH, ÂÚ˘ıÚÔÔÈËÙ›ÓË, ·˘ÍËÙÈ΋ ÔÚÌfiÓË Î.Ï. ∏ ∞CTH ·˘Í¿ÓÂÈ ÙË Ì˘˚΋ Ì¿˙· Î·È ÙË Ì˘˚΋ ÈÛ¯‡ Ì ÙËÓ ·‡ÍËÛË ÙˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ÛÙÔ ·›Ì·. ∏ ÂÚ˘ıÚÔÔÈËÙ›ÓË ÂÈÙ˘Á¯¿ÓÂÈ ÙËÓ ·‡ÍËÛË ÙˆÓ ÂÚ˘ıÚÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ ÙÔ˘ ·›Ì·ÙÔ˜ Î·È ÙË ÌÂÙ·ÊÔÚ¿ Ô͢ÁfiÓÔ˘ ÛÙÔ˘˜ ÈÛÙÔ‡˜. §fiÁˆ Ù˘ ·˘ÍË̤Ó˘ ËÎÙÈÎfiÙËÙ·˜ ÙÔ˘ ·›Ì·ÙÔ˜, ÌÔÚ› Ó· ÚÔÎÏËıÔ‡Ó ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘ Î·È ıÚÔÌ‚ÔÂÌ‚ÔÏÈο ÂÂÈÛfi‰È· ÛÙ· ÂÁÎÂÊ·ÏÈο Î·È ¿ÏÏ· ·ÁÁ›· (28,29). ∏ ·˘ÍËÙÈ΋ ÔÚÌfiÓË ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û˘Ó‹ıˆ˜ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·Ó·‚ÔÏÈο ÛÙÂÚÔÂȉ‹ ÁÈ· ÙËÓ ·‡ÍËÛË Ù˘ Ì˘˚΋˜ ‰‡Ó·Ì˘ (30). ¶·Ú¿ ÙËÓ Â˘Ú›· ¯Ú‹ÛË Ù˘ (31,32), ‰ÂÓ ˘¿Ú¯Ô˘Ó ·ԉ›ÍÂȘ ÁÈ· ÙËÓ ·‡ÍËÛË Ù˘ ·fi‰ÔÛ˘ ÛÙ· ‰È¿ÊÔÚ· ·ıÏ‹Ì·Ù· (΢ڛˆ˜ ÛÙËÓ ¿ÚÛË ‚·ÚÒÓ). ˙) ∫Ú·ٛÓË: ∞˘Í¿ÓÂÈ ÙË Ì˘˚΋ Ì¿˙·. ÃÚËÛÈÌÔÔÈÂ›Ù·È Î˘Ú›ˆ˜ ·fi fiÛÔ˘˜ ·Û¯ÔÏÔ‡ÓÙ·È Û˘ÛÙËÌ·ÙÈο Ì ÙË ÛˆÌ·ÙÔ‰fiÌËÛË (body-builders). Ë) °ÔÓȉȷÎfi ÓÙfiÈÓÁÎ: ∂ÂÌ‚·›ÓÔÓÙ·˜ ÁÔÓȉȷο Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÌÂÙ·ÙÚ·› Ë ·Ó·ÏÔÁ›· ÙˆÓ Ì˘˚ÎÒÓ ÈÓÒÓ Ì ·˘ÍË̤ÓË ‹ ÂÏ·Ùو̤ÓË Û˘ÛÙ·ÏÙÈÎfiÙËÙ·, ‚ÔËıÒÓÙ·˜ ¤ÙÛÈ ÙÔ˘˜ ·ıÏËÙ¤˜ ÙˆÓ ‰ÚfiÌˆÓ ÁÈ· ÌÈÎÚ¤˜ (sprinters) ‹ ÁÈ· ÌÂÁ¿Ï˜ (Ì·Ú·ıˆÓÔ‰ÚfiÌÔÈ) ·ÔÛÙ¿ÛÂȘ (33). ı) πÓÛÔ˘Ï›ÓË: ÃÚËÛÈÌÔÔÈÂ›Ù·È ˆ˜ ·Ó·‚ÔÏÈ΋ ÔÚÌfiÓË ÛÙ· ·ıÏ‹Ì·Ù· ‰‡Ó·Ì˘, fiˆ˜ Ë ¿ÚÛË ‚·ÚÒÓ. ¢ÂÓ ˘¿Ú¯ÂÈ ‚È‚ÏÈÔÁÚ·ÊÈ΋ ÙÂÎÌËÚ›ˆÛË ˆ˜ ÚÔ˜ ÙË ıÂÙÈ΋ Ù˘ Â›‰Ú·ÛË, ÙÔ˘Ó·ÓÙ›ÔÓ ˘¿Ú¯Ô˘Ó ·Ó·ÊÔÚ¤˜ ÁÈ· ˘ÔÁÏ˘Î·ÈÌÈο ÂÂÈÛfi‰È· (34,35). È) ™˘ÌÏËÚÒÌ·Ù· ‰È·ÙÚÔÊ‹˜ - ÔÏ˘‚ÈÙ·ÌÈÓÔ‡¯· Û΢¿ÛÌ·Ù·: À¿Ú¯ÂÈ ÌÂÁ¿ÏË ÔÈÎÈÏ›· ÔÏ˘‚ÈÙ·ÌÈÓÔ‡¯ˆÓ Û΢·ÛÌ¿ÙˆÓ, Ì ۯ‰fiÓ fiϘ ÙȘ ˘‰·ÙÔ‰È·Ï˘Ù¤˜ Î·È ÏÈÔ‰È·Ï˘Ù¤˜ ‚Èٷ̛Ә Û ‰È¿ÊÔÚ˜ ÂÚÈÂÎÙÈÎfiÙËÙ˜. ∂›Û˘, ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û·Ó Û˘Ìϋڈ̷ ‰È·ÙÚÔÊ‹˜ Û΢¿ÛÌ·Ù· Ì ̤ٷÏÏ·, ȯÓÔÛÙÔȯ›·, Âί˘Ï›ÛÌ·Ù· ‚ÔÙ¿ÓˆÓ Î.Ï. ™Â ·ÚÎÂÙ¤˜ ÂÚÈÙÒÛÂȘ, Èı·ÓÒ˜ Ù· ÂÚÈÛÛfiÙÂÚ· ·fi ·˘Ù¿ - Î·È È‰È·›ÙÂÚ· ÛÙȘ ÌÂÁ¿Ï˜ ‰fiÛÂȘ Ô˘ Û˘¯Ó¿ Û˘ÓÈÛÙÒÓÙ·È - Â›Ó·È ¿¯ÚËÛÙ· (16). È·) ∞Ó·„˘ÎÙÈο Ù‡Ô˘ sports drinks Î·È energy drinks: ¶·Ú’ fiÏÔ Ô˘ ¤¯ÂÈ Û˘˙ËÙËı› ·ÚÎÂÙ¿, Ù· sports drinks ‰ÂÓ Â›Ó·È ÂÈΛӉ˘Ó·, ·ÊÔ‡ ÛÙËÓ Ú·ÁÌ·ÙÈÎfiÙËÙ· Â›Ó·È ËÏÂÎÙÚÔÏ˘ÙÈο ‰È·Ï‡Ì·Ù·. ∆· energy drinks ÂÚȤ¯Ô˘Ó ΢ڛˆ˜ ηʽÓË, ·ÏÏ¿ Î·È ¿ÏϘ Ô˘Û›Â˜ fiˆ˜ ‚Èٷ̛Ә, Ù·˘Ú›ÓË Î.Ï. ™Â ηÓÔÓÈ΋ ¯Ú‹ÛË ‰ÂÓ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È ÚÔ‚Ï‹Ì·Ù·. ™ÙȘ ÂÚÈÙÒ-

ÛÂȘ, ˆÛÙfiÛÔ, Ô˘ ·Ó·ÌÂÈÁÓ‡ÔÓÙ·È Ì ¿ÏϘ ‡ÔÙ˜ Ô˘Û›Â˜ ‹ ÔÈÓÔÓÂ˘Ì·ÙÒ‰Ë ÔÙ¿, ÌÔÚ› Ó· ‰ËÌÈÔ˘ÚÁËıÔ‡Ó ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ fiˆ˜ ̤ıË Î.Ï. (13). ŸÏ· fiÛ· ·Ó·Ê¤ÚıËÎ·Ó ·ÔÙÂÏÔ‡Ó ¤Ó· ÌÈÎÚfi ̤ÚÔ˜ ÙˆÓ Ì¤ÛˆÓ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· ÓÙfiÈÓÁÎ. ∏ ·Ó·ÊÔÚ¿ Û ÂÚÈÛÛfiÙÂÚ· ı· ÍÂÂÚÓÔ‡Û ٷ fiÚÈ· ·˘ÙÔ‡ ÙÔ˘ ¿ÚıÚÔ˘. ¶Ú¤ÂÈ Ó· ÚÔÛÙÂı› fiÙÈ ÔÏÏ¿ ·fi Ù· Û΢¿ÛÌ·Ù·, ȉȷ›ÙÂÚ· ·˘Ù¿ Ô˘ ‰ÂÓ ·Ó‹ÎÔ˘Ó ÛÙËÓ Î·ÙËÁÔÚ›· ÙˆÓ Ê·Ú̿ΈÓ, ‰È·Ù›ıÂÓÙ·È ÂχıÂÚ· ·fi Ù· ÂȉÈο ηٷÛÙ‹Ì·Ù·, ÙÔ ‰È·‰›ÎÙ˘Ô ‹ Ù· Ê·Ú̷Λ·. ∂›Û˘, ı· Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ ÙÔ ÓÙfiÈÓÁÎ Â›Ó·È È‰È·›ÙÂÚ· ‰È·‰Â‰Ô̤ÓÔ Î·È ÛÙ· ˙Ò·, ΢ڛˆ˜ ÛÙ· ¿ÏÔÁ· ·ÁÒÓˆÓ (36-38).

¡ÙfiÈÓÁÎ Î·È ·È‰È¿ ™ÙȘ ÌÈÎÚ¤˜ ËÏÈ˘, ÛÙ· ·È‰È¿ ÙÔ˘ ‰ËÌÔÙÈÎÔ‡ ‹ ÛÙ· ÌÈÎÚfiÙÂÚ·, Ú·ÎÙÈο ‰ÂÓ ˘¿Ú¯ÂÈ ÓÙfiÈÓÁÎ. ™ÙËÓ ÂÊË‚È΋ ËÏÈΛ·, fiˆ˜ Î·È ÛÙÔ˘˜ Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ, ÔÈ Èı·ÓfiÙËÙ˜ ÙÔ˘ ÓÙfiÈÓÁÎ ·˘Í¿ÓÔÓÙ·È, ΢ڛˆ˜ fiÛÔÓ ·ÊÔÚ¿ ÛÙ· ·È‰È¿ Ô˘ οÓÔ˘Ó ÚˆÙ·ıÏËÙÈÛÌfi ‹ Û ·˘Ù¿ ÙˆÓ ÔÔ›ˆÓ ÔÈ ÂȉfiÛÂȘ ÙÔ˘˜ “˘fiÛ¯ÔÓÙ·È” ÌÂÏÏÔÓÙÈÎÔ‡˜ ÚˆÙ·ıÏËÙ¤˜ (39,40). ™ÙË ‚È‚ÏÈÔÁÚ·Ê›· ˘¿Ú¯Ô˘Ó ÌÂϤÙ˜ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ÔÛÔÛÙ¿ 1-2% ÛÙ· ÎÔÚ›ÙÛÈ· Î·È 3-12% ÛÙ· ·ÁfiÚÈ·. ™Â ¿ÏϘ ÌÂϤÙ˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Î·È Ù· ‰‡Ô ʇϷ, ·Ó·Ê¤ÚÔÓÙ·È ÔÛÔÛÙ¿ 36% (41,42). ∂Âȉ‹, fï˜, ÔÈ ÂÚÁ·Û›Â˜ ·˘Ù¤˜ Û˘Ó‹ıˆ˜ ÛÙËÚ›˙ÔÓÙ·È Û ÂÚˆÙËÌ·ÙÔÏfiÁÈ· Ô˘ Û˘ÌÏËÚÒÓÔÓÙ·È ·fi ÙÔ˘˜ ›‰ÈÔ˘˜ ÙÔ˘˜ ÂÊ‹‚Ô˘˜ ‹ ÙÔ˘˜ Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ, Â›Ó·È Èı·Ófi Ù· ÔÛÔÛÙ¿ ·˘Ù¿ Ó· Â›Ó·È Ôχ ÌÂÁ·Ï‡ÙÂÚ·. À¿Ú¯Ô˘Ó ÌÂϤÙ˜ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ·È‰È¿ ËÏÈΛ·˜ 12-15 ÂÙÒÓ, fiÔ˘ Ù· ÔÛÔÛÙ¿ ·Ó¤Ú¯ÔÓÙ·È Û 35%, ηıÒ˜ Î·È ¿ÏϘ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È Û ËÏÈ˘ ÌÂÁ·Ï‡ÙÂÚ˜ ÙˆÓ 17 ÂÙÒÓ, fiÔ˘ Ù· ÔÛÔÛÙ¿ ÊÙ¿ÓÔ˘Ó ÙÔ 80% (43,45). øÛÙfiÛÔ, fiÔÈ· Î·È ·Ó Â›Ó·È Ë Ú·ÁÌ·ÙÈ΋ Û˘¯ÓfiÙËÙ· ÙÔ˘ ÓÙfiÈÓÁÎ ÛÙËÓ ·È‰È΋ ËÏÈΛ·, Â›Ó·È ¿‰ÈÎÔ Ó· ‰ËÏËÙËÚÈ¿˙ÂÙ·È Ô ÂÓıÔ˘ÛÈ·ÛÌfi˜ ÙˆÓ ·È‰ÈÒÓ ÁÈ· ÙÔÓ ·ıÏËÙÈÛÌfi. ¢ÂÓ Ú¤ÂÈ Ó· ͯӿÌ fiÙÈ ·ıÏËÙÈÛÌfi˜ ÛËÌ·›ÓÂÈ ˘Á›·, ÂÈı·Ú¯›·, ·˘ÙÔÂÈı·Ú¯›·, Û˘ÏÏÔÁÈÎfi Ó‡̷, ¢ÁÂÓ‹˜ ¿ÌÈÏÏ·, ·ÔÊ˘Á‹ ‚Ï·‚ÂÚÒÓ Û˘ÓËıÂÈÒÓ Î·È ¿Óˆ ·’ fiÏ· ‰È·ÛΤ‰·ÛË Î·È ¯·Ú¿ (46). ∏ ¯Ú‹ÛË ··ÁÔÚÂ˘Ì¤ÓˆÓ Ô˘ÛÈÒÓ ÌÔÚ› Ó· ·ÓÙÈÌÂÙˆÈÛÙ› Ì ÂÓË̤ڈÛË, ÂÎ·›‰Â˘ÛË Î·È Ï‹ıÔ˜ ¿ÏÏˆÓ ÙÚfiˆÓ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙË Û˘Ó¤¯ÂÈ· (47). ¶·È‰È·ÙÚÈ΋ 2006;69:317-322

320

™. ∞ÓÙˆÓÈ¿‰Ë˜

™˘Ó¤ÂȘ ÙÔ˘ ÓÙfiÈÓÁÎ ™Â η̛· ÂÚ›ÙˆÛË ‰ÂÓ Ú¤ÂÈ Ó· ˘ÔÛÙËÚ›˙ÂÙ·È ‹ Ó· ÂÓı·ÚÚ‡ÓÂÙ·È ÔÔÈ·‰‹ÔÙ ÌÔÚÊ‹ ÓÙfiÈÓÁÎ. ¶·Ú’ fiÏ· ·˘Ù¿, fiˆ˜ Ê·›ÓÂÙ·È ·fi ÙȘ Ô˘Û›Â˜ Ô˘ ·Ó·Ê¤ÚıËηÓ, ˘¿Ú¯ÂÈ ÌÂÁ¿ÏË ‰È·ÊÔÚ¿ .¯. ÌÂٷ͇ Ù˘ ¯Ú‹Û˘ ηÊ½Ó˘ Î·È ÎÔη˝Ó˘, ‰ÈÔ˘ÚËÙÈÎÒÓ Î·È ÌÔÚÊ›Ó˘ Î.Ï. ∂ÎÙfi˜, fï˜, ·fi ÙÔ Â›‰Ô˜ Ù˘ Ô˘Û›·˜, ·˘Ùfi Ô˘ ηıÔÚ›˙ÂÈ ÙË ÛÔ‚·ÚfiÙËÙ· ÙˆÓ ‚Ï·‚ÒÓ Â›Ó·È Ë ‰fiÛË Î·È Ë ‰È¿ÚÎÂÈ· ¯Ú‹Û˘ Ù˘. √È ÌÈÎÚ¤˜ ‰fiÛÂȘ ‰ÂÓ ÚÔηÏÔ‡Ó È‰È·›ÙÂÚ· ÛÔ‚·Ú¤˜ ÂÈÙÒÛÂȘ, ·ÏÏ¿ Ë ·Ú·ÙÂٷ̤ÓË Î·È ˘ÂÚ‚ÔÏÈ΋ ¯Ú‹ÛË ÔÔÈ·Û‰‹ÔÙÂ Ô˘Û›·˜ - ·ÎfiÌË Î·È fiÙ·Ó ·˘Ù‹ Â›Ó·È Û¯ÂÙÈο ·ıÒ· - ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÛÔ‚·Ú¿ ÚÔ‚Ï‹Ì·Ù· ˘Á›·˜ (6,48,49). ∆· ÈÔ ÂÈΛӉ˘Ó· ÚÔ‚Ï‹Ì·Ù·, Ù· ÔÔ›· ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ÚÔηÏÔ‡Ó ÙÔÓ ı¿Ó·ÙÔ, ·ÊÔÚÔ‡Ó ÛÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ· (50,51). ∞Ó¿ÏÔÁ· Ì ÙÔ ¿ıÏËÌ·, ηٿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÚÔÔÓ‹ÛÂˆÓ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È ·ÏÏ·Á¤˜, ÔÈ Ôԛ˜ Â›Ó·È ··Ú·›ÙËÙ˜ ÁÈ· ÙËÓ ˘ÔÛÙ‹ÚÈÍË Ù˘ ΢ÎÏÔÊÔÚ›·˜ ÛÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ¿ıÏËÌ·. ™ÙÔ˘˜ ·ıÏËÙ¤˜ ‰ÚfïÓ, Ô˘ Â›Ó·È ··Ú·›ÙËÙÔ˜ ÌÂÁ·Ï‡ÙÂÚÔ˜ ηٿ ÏÂÙfi fiÁÎÔ˜ ·›Ì·ÙÔ˜, Ë Î·Ú‰È¿ ÌÂÙ·ÙÚ¤ÂÙ·È Û ÎÔÈÏfiÙËÙ· fiÁÎÔ˘. ∞˘Í¿ÓÔÓÙ·È ÔÈ ‰È·ÛÙ¿ÛÂȘ ÙˆÓ ÎÔÈÏÈÒÓ Î·È ÏÂÙ‡ÓÂÙ·È ÙÔ ÙÔ›¯ˆÌ¿ ÙÔ˘˜. ∏ ¯ˆÚËÙÈÎfiÙËÙ· - ·fi Ù· Ê˘ÛÈÔÏÔÁÈο ÂÚ›Ô˘ 600 ml ÌÔÚ›, .¯. Û ̷ڷıˆÓÔ‰ÚfiÌÔ˘˜, Ó· ÊÙ¿ÛÂÈ ¤ˆ˜ Î·È Ù· 1000 ml. ™ÙȘ ÂÚÈÙÒÛÂȘ ·ıÏËÌ¿ÙˆÓ fiˆ˜ Ë ¿ÚÛË ‚·ÚÒÓ, ·Ú·ÙËÚÂ›Ù·È ¿¯˘ÓÛË ÙÔ˘ Ì˘Ôηډ›Ô˘ ̤¯ÚÈ Î·È 13-15 mm. (Ê.Ù.

7-11 mm) Î·È ÂÏ¿ÙÙˆÛË ÙˆÓ ‰È·ÛÙ¿ÛÂˆÓ ÙˆÓ ÎÔÈÏÈÒÓ, ÂÓÒ Ë Î·Ú‰È¿ ÌÂÙ·ÙÚ¤ÂÙ·È Û ÎÔÈÏfiÙËÙ· ȤÛÂˆÓ (52). ¶·Ú¿ÏÏËÏ·, ·Ú·ÙËÚÔ‡ÓÙ·È ·ÏÏ·Á¤˜ Î·È ÛÙ· ÛÙÂÊ·ÓÈ·›· ·ÁÁ›·, Ë ‰È¿ÌÂÙÚÔ˜ ÙˆÓ ÔÔ›ˆÓ ÌÔÚ› Ó· ÊÙ¿ÓÂÈ Ì¤¯ÚÈ Î·È Ù· 7 ¯ÈÏÈÔÛÙ¿ (fiÙ·Ó Ë Ê˘ÛÈÔÏÔÁÈ΋ Â›Ó·È ÂÚ›Ô˘ 3 ¯ÈÏÈÔÛÙ¿) (53). Ÿˆ˜ Â›Ó·È Â˘ÓfiËÙÔ, ÔÈ Èı·ÓfiÙËÙ˜ ·Ó·ÛÙÚÔÊ‹˜ ÙˆÓ ·ÏÏ·ÁÒÓ ·˘ÙÒÓ Â›Ó·È Â˘ı¤ˆ˜ ·Ó¿ÏÔÁ˜ Ì ÙË ‰È¿ÚÎÂÈ·, ÙËÓ ¤ÓÙ·ÛË, ·ÏÏ¿ Î·È ÙÔ Â›‰Ô˜ ÙÔ˘ ·ıÏ‹Ì·ÙÔ˜. ∂›Û˘, ÌÔÚ› Ó· ÚÔÎÏËıÔ‡Ó ‚Ú·‰˘Î·Ú‰›·, ·ÚÚ˘ı̛˜, ˘¤ÚÙ·ÛË Î.Ï. ∂›Ó·È, ÂÔ̤ӈ˜, Ôχ ÛËÌ·ÓÙÈÎfi οı ·ıÏËÙ‹˜ - Î·È Î˘Ú›ˆ˜ ÚˆÙ·ıÏËÙ‹˜ - Ó· ÂϤÁ¯ÂÙ·È ÚÈÓ ·Ú¯›ÛÂÈ Ó· ·ıÏ›ٷÈ, ·ÏÏ¿ Î·È Û ٷÎÙ¿ ¯ÚÔÓÈο ‰È·ÛÙ‹Ì·Ù· (54,55). ™Ù· ÂÚÈÛÛfiÙÂÚ· ÂÚÈÛÙ·ÙÈο ı·Ó¿ÙˆÓ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›·, Ë ·ÈÙ›· ÂÓÙÔ›˙ÂÙ·È ÛÙÔ Î˘ÎÏÔÊÔÚÈÎfi Û‡ÛÙËÌ·, ÌÂ Û˘¯ÓfiÙÂÚÔ ÙÔ ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘. ø˜ ¿ÏϘ Û˘¯Ó¤˜ ·Èٛ˜ ı·Ó¿ÙˆÓ ·Ó·Ê¤ÚÔÓÙ·È Ù· ·ÁÁÂȷο ÂÁÎÂÊ·ÏÈο ÂÂÈÛfi‰È· ¶·È‰È·ÙÚÈ΋ 2006;69:317-322

(56,57), ηıÒ˜ Î·È ÔÈ ‚Ï¿‚˜ ÛÙÔ ‹·Ú (Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ·) Î·È ÙÔ˘˜ ÓÂÊÚÔ‡˜ (ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ·) Ô˘ ÔÊ›ÏÔÓÙ·È ÛÙËÓ Ë·ÙÔÙÔÍÈÎfiÙËÙ· Î·È ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· ÙˆÓ ‰È·ÊfiÚˆÓ Ô˘ÛÈÒÓ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙÔ ÓÙfiÈÓÁÎ (58). ªÔÏÔÓfiÙÈ Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ·ıÏËÙÒÓ ‰ÂÓ Ê·›ÓÂÙ·È Ó· ·Ó·Ù‡ÛÛÂÈ ÂÍ¿ÚÙËÛË ·fi οÔÈ· Ô˘Û›· Ô˘ ·˘Í¿ÓÂÈ ÙËÓ ·fi‰ÔÛË ‹ Ô˘ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÂıÈÛÌfi, ˆÛÙfiÛÔ Ô Î›Ó‰˘ÓÔ˜ Â›Ó·È ˘·ÚÎÙfi˜ (59).

∞ÓÙÈ-ÓÙfiÈÓÁÎ ¶·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÙÔ ÓÙfiÈÓÁÎ ‹Ù·Ó ÁÓˆÛÙfi ·fi ÙËÓ ÚÒÙË √Ï˘ÌÈ¿‰· Î·È ·Ú’ fiÏÔ Ô˘ ÛÙȘ √Ï˘ÌÈ¿‰Â˜ ÙˆÓ ÂÙÒÓ 1920-1930 ›¯Â Ï¿‚ÂÈ ÌÂÁ¿Ï˜ ‰È·ÛÙ¿ÛÂȘ, Ë ·ıÏËÙÈ΋ ÎÔÈÓfiÙËÙ· ÌfiÏȘ ÙÔ 1967 ¤Ï·‚ ٷ ÚÒÙ· ̤ÙÚ· ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛ‹ ÙÔ˘. √È ¤ÏÂÁ¯ÔÈ ·ÓÙÈ-ÓÙfiÈÓÁÎ ÂÊ·ÚÌfiÛÙËÎ·Ó ÁÈ· ÚÒÙË ÊÔÚ¿ ÛÙË ¯ÂÈÌÂÚÈÓ‹ √Ï˘ÌÈ¿‰· Ù˘ Grenoble Î·È ÛÙËÓ Î·ÏÔηÈÚÈÓ‹ ÙÔ˘ Mexico City ÙÔ 1968. ªfiÏȘ ÙÔÓ ¡Ô¤Ì‚ÚÈÔ ÙÔ˘ 1999 ȉڇıËÎÂ Ë ·ÁÎfiÛÌÈ· ÔÚÁ¿ÓˆÛË ·ÓÙÈ-ÓÙfiÈÓÁÎ (WADA), ÂÓÒ Ô ·ÁÎfiÛÌÈÔ˜ ÎÒ‰Èη˜ ·ÓÙÈ-ÓÙfiÈÓÁÎ „ËÊ›ÛÙËΠÙÔÓ π·ÓÔ˘¿ÚÈÔ ÙÔ˘ 2004 ÁÈ· Ó· ÂÊ·ÚÌÔÛÙ› ·fi ÙÔ 2006. π‰Ú‡ıËηÓ, Â›Û˘, ÂıÓÈÎÔ› ÔÚÁ·ÓÈÛÌÔ› ·ÓÙÈ-ÓÙfiÈÓÁÎ, fiˆ˜ Ë USADA, AADA Î.Ï. (60). ™ÙËÓ ∂ÏÏ¿‰· ˘¿Ú¯Ô˘Ó ÔÈ ÓfiÌÔÈ 2725/99 Î·È 3057/2002, ηıÒ˜ Î·È ÙÔ ∂ıÓÈÎfi ™˘Ì‚Ô‡ÏÈÔ ∫·Ù·ÔϤÌËÛ˘ ÙÔ˘ ¡ÙfiÈÓÁÎ (∂™∫∞¡). Ÿˆ˜ Ê·›ÓÂÙ·È ·fi ÙËÓ ·Ú·¿Óˆ Û‡ÓÙÔÌË ¯ÚÔÓÔÏÔÁÈ΋ ·Ú¿ıÂÛË, Ë ÔÚÁ·ÓˆÌ¤ÓË ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ÓÙfiÈÓÁΠηı˘ÛÙ¤ÚËÛ ÁÈ· ÂÚÈÛÛfiÙÂÚ· ·fi ÂηÙfi ¯ÚfiÓÈ·. ∆· ηٷÛÙ·ÏÙÈο ̤ÙÚ·, ÛÙ· ÔÔ›· ÌÔÚ› Ó· ˘¿ÚÍÂÈ Î·È ¤Ó·˜ ‚·ıÌfi˜ ÌÂÚÔÏË„›·˜, ‰ÂÓ Â›Ó·È Â‡ÎÔÏÔ Ó· ¤¯Ô˘Ó ·fiÏ˘Ù· ÈηÓÔÔÈËÙÈ΋ ·fi‰ÔÛË. °È· Ó· ·ÓÙÈÌÂÙˆÈÛÙ› ÙÔ ÓÙfiÈÓÁÎ ·ÔÙÂÏÂÛÌ·ÙÈο, οÙÈ Ô˘ - fiˆ˜ Ê·›ÓÂÙ·È - Â›Ó·È ·ÚÎÂÙ¿ ‰‡ÛÎÔÏÔ, ı· Ú¤ÂÈ Ó· ÏËÊıÔ‡Ó ˘’fi„ÈÓ Ôχ ÚÔÛÂÎÙÈο Ù· ·ÎfiÏÔ˘ı· (61-63): ·) Ÿˆ˜ ‹‰Ë ·Ó·Ê¤ÚıËÎÂ, “ÛÔ‚·Úfi” ÓÙfiÈÓÁÎ ¯ˆÚ›˜ ÙË Û˘ÌÌÂÙÔ¯‹, Û˘ÓÙ·ÁÔÁÚ¿ÊËÛË (64,65) Î·È Î·ıÔ‰‹ÁËÛË ÙˆÓ ÁÈ·ÙÚÒÓ ‰ÂÓ ÌÔÚ› Ó· Á›ÓÂÈ. °È· ÙÔÓ ÏfiÁÔ ·˘Ùfi ı· Ú¤ÂÈ Î·Ù’ ·Ú¯¿˜ Ó· ÂÓËÌÂÚˆıÔ‡Ó fiÏÔÈ ÔÈ ÁÈ·ÙÚÔ› ÁÈ· ÙÔ Ì¤ÁÂıÔ˜ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜, ÙȘ ‰È·ÛÙ¿ÛÂȘ Ô˘ ¤¯ÂÈ Ï¿‚ÂÈ Î·È ÙÔ˘˜ ÎÈÓ‰‡ÓÔ˘˜ ÁÈ· Ù· ·È‰È¿, ÙÔ˘˜ ·ıÏËÙ¤˜ Î·È ÙÔ˘˜ ÚˆÙ·ıÏËÙ¤˜. ∆Ô ÓÙfiÈÓÁÎ ı· Ú¤ÂÈ Ó· ·ÓÙÈÌÂÙˆ›˙ÂÙ·È fiˆ˜ οı ¿ÏÏÔ Úfi‚ÏËÌ· ‰ËÌfiÛÈ·˜ ˘Á›·˜ (οÓÈÛÌ·,

321

¡ÙfiÈÓÁÎ Û ·È‰È¿, ÂÊ‹‚Ô˘˜ Î·È Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ

ÔÈÓÔÓÂ˘Ì·ÙÒ‰Ë, Ó·ÚΈÙÈο Î.Ï.). √ ÁÈ·ÙÚfi˜ Ô˘ ÁÓˆÚ›˙ÂÈ ÙȘ ÂÈÏÔΤ˜ Ù˘ ¯Ú‹Û˘ ÙˆÓ ‰È·ÊfiÚˆÓ ÌÂıfi‰ˆÓ/Ô˘ÛÈÒÓ, ı· Ú¤ÂÈ Ó· Â›Ó·È Î·È Ô ÚÒÙÔ˜ Ô˘ ı· οÓÂÈ ÙË ÛˆÛÙ‹ ÂÓË̤ڈÛË. ¶·Á›‰Â˜ fiˆ˜ ÔÈ ·Ú·ÎÏ‹ÛÂȘ ·fi ÙÔÓ ÚˆÙ·ıÏËÙ‹ ‹ ·ÎfiÌË Î·È ÙÔ ·ÎÚ·›Ô Ê·ÈÓfiÌÂÓÔ Ù˘ ·Ú¿ÎÏËÛ˘ ·fi ÁÔÓ›˜ ÁÈ· ÓÙÔ¿ÚÈÛÌ· ÙÔ˘ ·È‰ÈÔ‡ ÙÔ˘˜ Ì ÛÎÔfi ÙËÓ ÂÈÙ˘¯›·, Û›ÁÔ˘Ú· Â›Ó·È Â‡ÎÔÏÔ Ó· ·ÔÊ¢¯ıÔ‡Ó ·fi ÙÔ˘˜ ÁÈ·ÙÚÔ‡˜. ∏ ‰Â ÛˆÛÙ‹ ÂÓË̤ڈÛË Î·È ÂÎ·›‰Â˘ÛË, ΢ڛˆ˜ ÙˆÓ ÂÊ‹‚ˆÓ Î·È ÙˆÓ Ó·ÚÒÓ ÂÓËϛΈÓ, Ê·›ÓÂÙ·È fiÙÈ Ú¿ÁÌ·ÙÈ ·Ô‰›‰ÂÈ, ·ÊÔ‡ Û ¤Ó· ÛËÌ·ÓÙÈÎfi ÔÛÔÛÙfi Ë ¯Ú‹ÛË Á›ÓÂÙ·È ¯ˆÚ›˜ ÙË ÁÓÒÛË ÙˆÓ Û˘ÓÂÂÈÒÓ (66). ‚) £· Ú¤ÂÈ - ÛÂ Û˘ÓÂÓÓfiËÛË Ì ÙÔ˘˜ ÁÈ·ÙÚÔ‡˜ - Ó· Û˘ÌʈÓËı› ·fi fiÏÔ˘˜ ÙÔ˘˜ ÂÌÏÂÎfiÌÂÓÔ˘˜ (·ıÏËÙ¤˜, ÚÔÔÓËÙ¤˜, Û˘ÏÏfiÁÔ˘˜, ÔÌÔÛÔÓ‰›Â˜ Î.Ï.) Â¿Ó ÂÈı˘ÌÔ‡Ó ÙÔ ÓÙfiÈÓÁÎ ÛÙÔÓ ·ıÏËÙÈÛÌfi ‹ fi¯È. ∂›Ó·È ÛËÌ·ÓÙÈÎfi ·˘Ù‹ Ë Û˘ÓÂÓÓfiËÛË Ó· Â›Ó·È ·fiÏ˘ÙË, ηıÒ˜ Ë ¯Ú‹ÛË ÓÙfiÈÓÁÎ ·fi ÔÚÈṲ̂ÓÔ˘˜ ÌfiÓÔ ·ıÏËÙ¤˜ Ô‰ËÁ› ·˘ÙfiÌ·Ù· Û ·ÔÙ˘¯›· fiÛÔ˘˜ ÙËÓ Î·Ù·‰Èο˙Ô˘Ó. ¢˘ÛÙ˘¯Ò˜, ˘¿Ú¯Ô˘Ó ·ıÏËÙ¤˜, ·Ú¿ÁÔÓÙ˜ ‹ ·ÎfiÌË Î·È ÁÈ·ÙÚÔ› Ô˘ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ¯ÚËÛÈÌÔÔ›ËÛË ‰È·ÊfiÚˆÓ ·ı¤ÌÈÙˆÓ ÌÂıfi‰ˆÓ Î·È Ô˘ÛÈÒÓ ÛÙÔÓ ·ıÏËÙÈÛÌfi, ÛÙÔ Ï·›ÛÈÔ Ù˘ ÂÏ¢ıÂÚ›·˜ ÛÙËÓ ÂÈÏÔÁ‹ Î·È Ù˘ ·ÙÔÌÈ΋˜ ¢ı‡Ó˘ (67). √ “ηı·Úfi˜” ·ıÏËÙÈÛÌfi˜ Â›Ó·È Ë ‚·ÛÈ΋ Âȉ›ˆÍË (68), ·ÏÏ¿ Â›Ó·È È‰È·›ÙÂÚ· ‰‡ÛÎÔÏÔ Ó· ˘¿ÚÍÂÈ Î·ıÒ˜ ÚÔ¸Ôı¤ÙÂÈ ·ÏÏ·Á‹ ÓÔÔÙÚÔ›·˜ ·¤Ó·ÓÙÈ ÛÙË ˙ˆ‹ ·ÏÏ¿ Î·È ÛÙÔÓ ·ıÏËÙÈÛÌfi. √ ·ıÏËÙ‹˜ ı· Ú¤ÂÈ Ó· ÈηÓÔÔÈÂ›Ù·È Ì fi,ÙÈ ÚÔÛʤÚÂÈ ÛÙËÓ ˘Á›· Î·È ÙÔ Ó‡̷ ÙÔ˘ Ë ÛˆÌ·ÙÈ΋ ¿ÛÎËÛË Î·È Ó· ·ÚÎÂ›Ù·È Û ·˘Ù¿ fiÙ·Ó ÙÔ ÛÒÌ· ÙÔ˘ ‰ÂÓ ‰È·ı¤ÙÂÈ ÙȘ ··Ú·›ÙËÙ˜ ‰˘Ó¿ÌÂȘ Î·È ·ÓÙÔ¯¤˜ ÁÈ· ˘„ËϤ˜ ÂȉfiÛÂȘ Î·È ‰È¿ÎÚÈÛË (69).

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AÏÏËÏÔÁÚ·Ê›·: ∫ˆÓÛÙ·ÓÙ›ÓÔ˜ ™ÙÂÊ·Ó›‰Ë˜ stefanid@hol.gr

¶ÔÈ· Â›Ó·È Ë Èı·Ó‹ ‰È¿ÁÓˆÛË;

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

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

¶·È‰È¿ Î·È ∆¤¯ÓË ∏ ¤ÊÂÛË ÁÈ· Ù¤¯ÓË Â›Ó·È, fiˆ˜ ηϿ ÁÓˆÚ›˙Ô˘ÌÂ, ¤ÌÊ˘ÙË ÛÙȘ ÌÈÎÚ¤˜ ËÏÈ˘. °È· Ó· ı·˘Ì¿ÛÔ˘Ì ‰ËÌÈÔ˘ÚÁ›Â˜ ÌÈÎÚÒÓ Î·ÏÏÈÙ¯ÓÒÓ, ·ÏÏ¿ ηÈ, ÁÈ·Ù› fi¯È, Ó· ÚÔÙÚ¤„Ô˘ÌÂ Î·È Ù· ‰Èο Ì·˜ ·È‰È¿ Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó, ·ÚÔ˘ÛÈ¿˙Ô˘Ì ÛÙÔ Ù‡¯Ô˜ ·˘Ùfi ‰È·‰ÈÎÙ˘·ÎÔ‡˜ ÙfiÔ˘˜ Ô˘ ÂÚȤ¯Ô˘Ó ·È‰È΋ ˙ˆÁÚ·ÊÈ΋.

Arts and Kids - http://www.artsandkids.com ∆Ô Arts and Kids ¤¯ÂÈ ˆ˜ ÛÙfi¯Ô ÙËÓ ·ÚÔ˘Û›·ÛË Ó·ÚÒÓ Î·ÏÏÈÙ¯ÓÒÓ ÛÙÔ Â˘Ú‡ ÎÔÈÓfi. √ÚÁ·ÓÒÓÂÈ ‰È·ÁˆÓÈÛÌÔ‡˜ ˙ˆÁÚ·ÊÈ΋˜ ÁÈ· ·È‰È¿, ÙÔ˘˜ ‰›ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ÛÙ›ÏÔ˘Ó Â˘¯ÂÙ‹ÚȘ οÚÙ˜, Ó· χÓÔ˘Ó ·˙Ï ·fi ÂÈÎfiÓ˜ Ô˘ ¤¯Ô˘Ó ˙ˆÁÚ·Ê›ÛÂÈ ·È‰È¿, ÂÓÒ ˘¿Ú¯ÂÈ Î·È Ë ‰˘Ó·ÙfiÙËÙ· ˙ˆÁÚ·ÊÈ΋˜ ¿Óˆ Û ÚfiÙ˘· online. µ¤‚·È·, ‰ÂÓ Ï›ÂÈ Ë ¤ÎıÂÛË (gallery) Ë ÔÔ›· ¤¯ÂÈ ÙË ÌÔÚÊ‹ ‚ÈÓÙÂÔ·ÚÔ˘Û›·Û˘ Ì ¢¯¿ÚÈÛÙË ÌÔ˘ÛÈ΋ ˘fiÎÚÔ˘ÛË.

Natural Child Project - http://www.naturalchild.com/gallery/ ∆Ô Natural Child Project, ÌÈ· ÎÔÈÓˆÊÂÏ‹˜ ÂÙ·ÈÚ›· Ì ÛÙfi¯Ô ÙË Û˘ÓÔÏÈÎfiÙÂÚË ˘ÔÛÙ‹ÚÈÍË ÙˆÓ ·È‰ÈÒÓ, ÂÚÈÏ·Ì‚¿ÓÂÈ ÌÈ· Ôχ ÂӉȷʤÚÔ˘Û· ¤ÎıÂÛË Ì ÂÚÈÛÛfiÙÂÚ˜ ·fi 1.000 ˙ˆÁÚ·ÊȤ˜ ·È‰ÈÒÓ ·’ fiÏÔ ÙÔÓ ÎfiÛÌÔ. ªÔÚ› ηÓ›˜ Ó· ·ÁÔÚ¿ÛÂÈ Î¿ÚÙ˜ ·fi ÙȘ ‰ËÌÈÔ˘ÚÁ›Â˜ ·˘Ù¤˜ Ô˘ Â›Ó·È ÔÌÔÏÔÁÔ˘Ì¤Óˆ˜ ÂÍ·ÈÚÂÙÈΤ˜.

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NEWS FROM THE INTERNET

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Kids’ Space - http://www.kids-space.org/ ŒÓ· ·ÎfiÌË ›‰Ú˘Ì· Ì ÂÎ·È‰Â˘ÙÈÎfi ¯·Ú·ÎÙ‹Ú·, ÙÔ ∫ids’ Space, ¤¯ÂÈ ˆ˜ ÛÙfi¯Ô ÙË ‚ÂÏÙ›ˆÛË Ù˘ ÂÎ·È‰Â˘ÙÈ΋˜ ÂÌÂÈÚ›·˜ ̤ۈ ‰È·‰ÈÎÙ‡Ô˘, ÙËÓ ·ÔÌ˘ıÔÔ›ËÛË ÙÔ˘ Internet Î·È ÙË ¯Ú‹ÛË ÙÔ˘ ˆ˜ ¿ÍÔÓ· ·ÁÎfiÛÌÈ·˜ Î·È ‰È·ÔÏÈÙÈÛÌÈ΋˜ ÂÈÎÔÈÓˆÓ›·˜. ∂‰Ò ÔÈ ˙ˆÁÚ·ÊȤ˜ Ù˘ ¤ÎıÂÛ˘ Û˘Óԉ‡ÔÓÙ·È ·fi ÈÛÙÔڛ˜: Î·È Ì¿ÏÈÛÙ·, ÌÔÚ› ηÓ›˜ Ó· ÁÚ¿„ÂÈ ÌÈ· ÈÛÙÔÚ›· ÁÈ· ÙËÓ ÂÈÎfiÓ· Ô˘ ¤¯ÂÈ ˙ˆÁÚ·Ê›ÛÂÈ Î¿ÔÈÔ˜ ¿ÏÏÔ˜ Î·È ·ÓÙ›ÛÙÚÔÊ·! ªÔÚ› ηÓ›˜ Ó· ÂÚ¿ÛÂÈ ¤ÙÛÈ ·ÚÎÂÙ¤˜ ¢¯¿ÚÈÛÙ˜ ÒÚ˜.

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

¶·È‰È·ÙÚÈ΋ 2006;69:324-325

326

CLINICAL QUIZ ∫ÏÈÓÈÎfi QUIZ ∞¶∞¡∆∏™∏

∏ ‰È¿ÁÓˆÛË Â›Ó·È ÌÂÁ·Î·Ï‡ÎˆÛË ‹ ÓfiÛÔ˜ ÙÔ˘ Puigvert, Ë ÔÔ›· ‚·Û›ÛÙËΠÛÙÔ Ù˘ÈÎfi ‡ÚËÌ· Ù˘ ‰È¿Ù·Û˘ ÙˆÓ Î·Ï‡ÎˆÓ, ¯ˆÚ›˜ Ó· Û˘Ó˘¿Ú¯ÂÈ ‰È¿Ù·ÛË Ù˘ ˘¤ÏÔ˘ (1-3). ™Â ·ÓÙ›ıÂÛË Ì ÙË ÌÂÁ·Î·Ï‡ÎˆÛË, ÛÙË ÛÙ¤ÓˆÛË Ù˘ ˘ÂÏÔÔ˘ÚËÙËÚÈ΋˜ Û˘Ì‚ÔÏ‹˜ ‰È·ÈÛÙÒÓÂÙ·È ÛËÌ·ÓÙÈ΋ ‰È¿Ù·ÛË ÙfiÛÔ Ù˘ ˘¤ÏÔ˘, fiÛÔ Î·È ÙˆÓ Î·Ï‡ÎˆÓ, ηıÒ˜ Î·È ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù· ÛÙÔ ‰˘Ó·ÌÈÎfi ÛÈÓıËÚÔÁÚ¿ÊËÌ· ÓÂÊÚÒÓ Ì 99mTc ÌÂÚηÙÔ-·ÎÂÙ˘ÏÔ-ÙÚÈÁÏ˘Î›ÓË (MAG3). ∂ÈϤÔÓ, Ù· ·È‰È¿ Ì ÌÂÁ·Î·Ï‡ÎˆÛË ‰ÂÓ ¤¯Ô˘Ó Â˘Ú‹Ì·Ù· ·fiÊڷ͢ ÛÙÔ ‰˘Ó·ÌÈÎfi ÛÈÓıËÚÔÁÚ¿ÊËÌ· MAG3. ∏ ‰È¿ÁÓˆÛË Ù˘ ÌÂÁ·Î·Ï‡ÎˆÛ˘ ÂȂ‚·ÈÒÓÂÙ·È Ì ٷ Ù˘Èο Â˘Ú‹Ì·Ù· ÛÙËÓ ÂÓ‰ÔÊϤ‚ÈÔ ˘ÂÏÔÁÚ·Ê›·. ™˘Ó‹ıˆ˜ ˘¿Ú¯ÂÈ Î·ı˘ÛÙ¤ÚËÛË ÛÙËÓ ·ÂÈÎfiÓÈÛË ÙˆÓ Î·Ï‡ÎˆÓ, ÏfiÁˆ ÙÔ˘ ÌÂÁ¿ÏÔ˘ fiÁÎÔ˘ ÙÔ˘˜ (2). ∂›Û˘ Â›Ó·È ‰˘Ó·Ùfi Ó· ‰È·ÈÛÙˆı› ¯·ÌËÏfi ÂȉÈÎfi ‚¿ÚÔ˜ Ô‡ÚˆÓ ·fi ·ÓÂ·Ú΋ ‰˘Ó·ÙfiÙËÙ· Û˘Ì‡ÎÓˆÛ˘, Èı·ÓÒ˜ ÏfiÁˆ ÂÏ¿ÙÙˆÛ˘ ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ·Ú·Ì˘ÂÏÈÎÒÓ ÓÂÊÚÒÓˆÓ (2). ∏ Ì·ÁÓËÙÈ΋ Ô˘ÚÔÁÚ·Ê›· (Magnetic Resonance Urography, MRU), ·Ú¤¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ï‹„˘ ÙfiÛÔ ·Ó·ÙÔÌÈÎÒÓ fiÛÔ Î·È ÏÂÈÙÔ˘ÚÁÈÎÒÓ ÏËÚÔÊÔÚÈÒÓ Î·È ÈÛÙ‡ÂÙ·È fiÙÈ ÛÙÔ Ì¤ÏÏÔÓ ı· Û˘Ì‚¿ÏÂÈ ÛÙË ‰È¿ÁÓˆÛË ·˘Ù‹˜ Ù˘ Û¿ÓÈ·˜ ·ÓˆÌ·Ï›·˜, ηıÒ˜ Î·È ¿ÏÏˆÓ Û‡ÓıÂÙˆÓ Ô˘ÚÔÏÔÁÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ (Riccabona/04). ªÂÙ¿ ·fi ÙËÓ ÚÒÙË ÂÚÈÁÚ·Ê‹ Ù˘ ÌÂÁ·Î·Ï‡ÎˆÛ˘ ·fi ÙÔÓ Puigvert ÙÔ 1964, ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Ï›Á˜ ÂÚÈÙÒÛÂȘ. ∏ ‰È¿ÁÓˆÛË Û˘Ó‹ıˆ˜ Á›ÓÂÙ·È ÛÙ· Ï·›ÛÈ· ·ÂÈÎÔÓÈÛÙÈÎÔ‡ ÂϤÁ¯Ô˘ ·È‰ÈÒÓ Ì ԢÚÔÏԛ̈ÍË ‹ Ì ÚÔÁÂÓ-

ÓËÙÈο ‰È·ÁÓˆṲ̂ÓË ˘‰ÚÔÓ¤ÊÚˆÛË (4,5). ™˘Ó‹ıˆ˜ Â›Ó·È ÂÙÂÚfiÏ¢ÚË (80%) Î·È ‰È·ÈÛÙÒÓÂÙ·È ÈÔ Û˘¯Ó¿ ÛÙ· ·ÁfiÚÈ· (90%) (5). ∏ ·ÈÙÈÔÏÔÁ›· Ù˘ Â›Ó·È ¿ÁÓˆÛÙË, ¤¯ÂÈ fï˜ ·Ô‰Ôı› Û ηı˘ÛÙ¤ÚËÛË Ù˘ Â·Ó·˘ÏÔÔ›ËÛ˘ ÙÔ˘ ¿Óˆ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ÂÌ‚Ú˘˚ÎÔ‡ Ô˘ÚËÙ‹Ú· ÌÂÙ¿ ÙË Û‡Ó‰ÂÛË ÙÔ˘ ÂÌ‚Ú˘˚ÎÔ‡ ÎÔÌ‚›Ô˘ ÛÙÔÓ ÌÂÙ¿ÓÂÊÚÔ (2). ™˘¯Ó¿ ˘¿Ú¯ÂÈ ÔÈÎÔÁÂÓÂȷ΋ ÂÈ‚¿Ú˘ÓÛË Î·È ¤¯ÂÈ ÂÚÈÁÚ·Ê› ÎÏËÚÔÓÔÌÈÎfiÙËÙ· Ì ÙÔÓ ˘ÔÏÂÈfiÌÂÓÔ ÛˆÌ·ÙÈÎfi ¯·Ú·ÎÙ‹Ú· (6). ∏ ÌÂÁ·Î·Ï‡ÎˆÛË Â›Ó·È Û˘Ó‹ıˆ˜ Ì›· ÌÂÌÔӈ̤ÓË ·ÓˆÌ·Ï›·, fï˜, ¤¯ÂÈ ‰È·ÈÛÙˆı› Î·È Û ·È‰È¿ Ì ۇÛÙÔÈ¯Ô ÌÂÁ·Ô˘ÚËÙ‹Ú· (5), ÏÂÈÔ΢ÛÙÈÎfi ‰˘ÛÏ·ÛÙÈÎfi ÓÂÊÚfi (6) ‹ Ì ۇӉÚÔÌÔ Schinzel-Giedion (ÚÔ˚Ô‡Û· Ó¢ÚÔÂÎÊ˘ÏÈÛÙÈ΋ ÓfiÛÔ˜ Ì ÔÙÈΤ˜ Î·È ÔÛÙÈΤ˜ ‚Ï¿‚˜) (7). ∏ ÚfiÁÓˆÛË Â›Ó·È Î·Ï‹. √È ·ÛıÂÓ›˜ ¤¯Ô˘Ó Ê˘ÛÈÔÏÔÁÈ΋ ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, fï˜, Ë ·ÓˆÌ·Ï›· ·˘Ù‹ ıˆÚÂ›Ù·È fiÙÈ Úԉȷı¤ÙÂÈ Û ԢÚÔÏÔÈÌÒÍÂȘ Î·È ÓÂÊÚÔÏÈı›·ÛË. ŒÙÛÈ, ÔÈ ·ÛıÂÓ›˜ Ì ÙÔ Úfi‚ÏËÌ· ·˘Ùfi Ú¤ÂÈ Ó· ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È Û˘ÛÙËÌ·ÙÈο, ÙfiÛÔ ÎÏÈÓÈο, fiÛÔ Î·È ˘ÂÚ˯ÔÁÚ·ÊÈο. ∏ Û¿ÓÈ· ·˘Ù‹ ·ÓˆÌ·Ï›· ÙÔ˘ Ô˘ÚÔÔÈËÙÈÎÔ‡ ÁÈ· ÙÔ˘˜ ÂÚÈÛÛfiÙÂÚÔ˘˜ ·È‰È¿ÙÚÔ˘˜ Â›Ó·È Ì›· “ͯ·Ṳ̂ÓË ‰È¿ÁÓˆÛË” [1]. ∆· ·ÂÈÎÔÓÈÛÙÈο Â˘Ú‹Ì·Ù· Â›Ó·È Ù˘Èο Î·È Ú¤ÂÈ Ë ÌÂÁ·Î·Ï‡ÎˆÛË Ó· Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ ÓÂÔÁÓÔ‡ Ì ÚÔÁÂÓÓËÙÈ΋ ˘‰ÚÔÓ¤ÊÚˆÛË. ¶ÚfiÛÊ·Ù· ¤¯ÂÈ ‰È·ÈÛÙˆı› ·Ó·Óˆ̤ÓÔ ÂӉȷʤÚÔÓ ÁÈ· ÙË ÌÂÁ·Î·Ï‡ÎˆÛË, ÁÈ·Ù› Ì ÙË ÛˆÛÙ‹ ‰È¿ÁÓˆÛË ·ÔʇÁÔÓÙ·È ÔÈ ÂÚÈÙÙ¤˜ ÂÍÂÙ¿ÛÂȘ Î·È ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Redman JF, Neeb AD. Congenital megacalycosis: a forgotten diagnosis? Urology 2005;65:384-385.

2. Kasap B, Kavukcu S, Soylu A, Turkmen M, Secil M. Megacalycosis: report of two cases. Pediatr Nephrol 2005;20:828-830.

3. Alivanis P, Giannikouris I, Arvanitis A, Volanaki M, Zervos A, Paliuras C. Bilateral congenital megacalycosis in a young male patient. Nephrol Dial Transplant 2006;21:1446-1447.

4. Hill LM, Macpherson T, Romano L, Gahagan S. Prenatal sonographic findings of fetal megacalycosis. J Ultrasound Med 2002;21:1179-1181.

5. Vidal Company A, Gonzalvez Pinera J, Ruiz Cano R, Gutierrez Junquera C, Lillo Lillo M. Megacalycosis

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diagnosed during the study of antenatal hydronephrosis. An Esp Pediatr 2001;54:74-77.

Lam AH. Familial megacalyces with autosomal recessive inheritance. Pediatr Radiol 1988;19:28-30.

Mandell GA, Snyder HM 3rd, Heyman S, Keller M, Kaplan JM, Norman ME Association of congenital megacalycosis and ipsilateral segmental megaureter.

Pediatr Radiol 1987;17:28-33.

Perera Soler R, Ruiz Gonzalez AP, Molini Menchon N, Garcia Nieto VM. Unilateral multicystic dysplastic kidney and contralateral megacalycosis. An unusual association. An Pediatr 2004;60:473-476.

Minn D, Christmann D, De Saint-Martin A, Alembik Y, Eliot M, Fischbach M, et al. Further clinical and sensorial delineation of Schinzel-Giedion syndrome: report of two cases. Am J Med Genet. 2002 1;109: 211-217.

¶ƒ√™∂Ã∏ ™À¡∂¢ƒπ∞ 4-7 ™ÂÙÂÌ‚Ú›Ô˘ 2006

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30th UMEMPS Congress Contact: Eng Rasha Hasan Tel.: 00963 9274 5746 Fax: 00963 1123 13326 E-mail: info@umemps30-sy.com Website: www.umemps30-sy.com

Damascus, Syria

14-16 ™ÂÙÂÌ‚Ú›Ô˘ 2006 5th International Neonatal Hematology and Immunology Meeting Contact: Gaetano Chirico Tel.: 39-0-303-995-219 Fax: 39-0-303-700-817 E-mail: gaechir@tin.it

Brescia, Italy

18-21 ™ÂÙÂÌ‚Ú›Ô˘ 2006 38th Congress of the International Society of Paediatric Oncology Contact: Sandrine Haemmerli Tel.: 41 223 399 648 Fax: 41 223 399 601 E-mail: siop2006@mci-group.com

Geneva, Switzerland

21-23 ™ÂÙÂÌ‚Ú›Ô˘ 2006 12o E˘Úˆ·˚Îfi ™˘Ó¤‰ÚÈÔ Ù˘ ¢ÈÂıÓÔ‡˜ √ÚÁ¿ÓˆÛ˘ ÁÈ· ÙËÓ ˘Á›· ÙˆÓ ∂Ê‹‚ˆÓ Hotel Grecotel Athens Imperial ¶ÏËÚÔÊÔڛ˜: ∫·ı. °ÂÒÚÁÈÔ˜ ÃÚÔ‡ÛÔ˜ ∆ËÏ./Fax: 210 7794023 √ÚÁ¿ÓˆÛË: PRC Congress & Travel, ∆ËÏ.: 210 7711673 Fax: 210 7711289 E-mail: secretariat@prctravel.gr

∞ı‹Ó·

22-24 ™ÂÙÂÌ‚Ú›Ô˘ 2006 ∂ÈÛÙËÌÔÓÈ΋ ™˘Ó¿ÓÙËÛË °ÓˆÚÈÌ›·˜ ™Î·Êȉȿ Ù˘ ∂ÏÏËÓÈ΋˜ ∞η‰ËÌ›·˜ ¶·È‰È·ÙÚÈ΋˜ Ì ∏Ï›· ÙÔ˘˜ ŒÏÏËÓ˜ ¶·È‰›·ÙÚÔ˘˜ ªÂ ÙË Û˘ÓÂÚÁ·Û›· Ù˘ ∂ÏÏËÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ ∂Ù·ÈÚ›·˜ •ÂÓÔ‰Ô¯Â›Ô Aldemar Olympian Village ¢ÈÔÚÁ¿ÓˆÛË Û˘Ó‰ڛԢ: Firstevent Prousis 3 st, 10440 Athens, Greece Tel.:+30 2108228950 Fax: +30 2108228901 E-mail: info@firstevent.gr Website: www.firstevent.gr 28 ™ÂÙÂÌ‚Ú›Ô˘ 1 √ÎÙˆ‚Ú›Ô˘ 2006

18Ô ¶·ÓÂÏÏ‹ÓÈÔ ™˘Ó¤‰ÚÈÔ ¶·È‰›, ÀÁ›· Î·È ¶ÔÏÈÙÈÛÌfi˜ ∆Ì‹Ì· π·ÙÚÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∫Ú‹Ù˘ ¢ÈÔÚÁ¿ÓˆÛË: ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ∫ÔÈÓˆÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶ÚÔ·ÁˆÁ‹˜ Ù˘ ÀÁ›·˜ ¶ÏËÚÔÊÔڛ˜: ∂ÚÁ·ÛÙ‹ÚÈÔ ÀÁÈÂÈÓ‹˜ Î·È ∂ȉËÌÈÔÏÔÁ›·˜ π·ÙÚÈ΋ ™¯ÔÏ‹, ¶·ÓÂÈÛÙ‹ÌÈÔ ∞ıËÓÒÓ ª. ∞Û›·˜ 75, 11527 ∞ı‹Ó· ∆ËÏ.: 210-7462201 Fax: 210-7462105

∏Ú¿ÎÏÂÈÔ ∫Ú‹ÙË

xxviii

5-8 √ÎÙˆ‚Ú›Ô˘ 2006

Advances in Paediatric Gastroenterology, Hepatology & Nutrition Turkish - Greek Joint Postgraduate Course endorsed by ESPGHAN ¶ÏËÚÔÊÔڛ˜: ∞ÏÂÍ¿Ó‰Ú· ¶··‰ÔÔ‡ÏÔ˘, ¶Úfi‰ÚÔ˜ ∂∂¶°∏¢ ∆ËÏ.: 210 77 26 355 E-mail: papadop5@otenet.gr ∂ÁÁڷʤ˜: Prof. Ender Pehlivanoglou, Marmara University, Istanbul Fax: 90 212 296 5481 E-mail: e.pehlivanoglu@tnn.net

Cappadocia, Turkey

7-10 √ÎÙˆ‚Ú›Ô˘ 2006

40th Meeting of the European Society of Paediatric Nephrology ¶ÏËÚÔÊÔڛ˜: E.DI.PO. s.r.l.Via della Libertà, 103 - 90143 Palermo ∆ËÏ.: ++39 091 340255 Fax: ++39 091 340440 E-mail: edi.po@tiscali.it Website: www.espn2006.org/

Palermo, Italy

29-31 √ÎÙˆ‚Ú›Ô˘ 2006

International Conference on Childhood Cancer Contact: Dr. Alireza Mosavi-Jarrahi ∆el.: 98 2 122 481 011 Fax: 98 2 122 481 010 E-mail: rmosavi@yahoo.com

Tehran, Iran

8-11 √ÎÙˆ‚Ú›Ô˘ 2006

European Academy of Paediatrics – CESP 2006 Centre Convencions Internacional Barcelona ¶ÏËÚÔÊÔڛ˜: Kenes International / Europaediatrics 2006 17 Rue du Cendrier PO Box 1726, CH-1211 Geneva 1, Switzerland Tel: +41 22 908 0488 Fax: +41 22 732 2850 E-mail: europaediatrics@kenes.com Website: www.kenes.com/europaediatrics

Barcelona, Spain

9-10 √ÎÙˆ‚Ú›Ô˘ 2006

∞ÓÙÈÌÂÙÒÈÛË ·È‰ÈÒÓ Ì ¢È·Ù·Ú·¯‹ ∂ÏÏÂÈÌÌ·ÙÈ΋˜ ∞ı‹Ó· ¶ÚÔÛÔ¯‹˜-ÀÂÚÎÈÓËÙÈÎfiÙËÙ·˜ ·fi ÂÎ·È‰Â˘ÙÈÎÔ‡˜ – ¶ÚfiÁÚ·ÌÌ· ÂÎ·›‰Â˘Û˘ ‰·ÛÎ¿ÏˆÓ Î·È Î·ıËÁËÙÒÓ ¶ÏËÚÔÊÔڛ˜: ∂æÀÀ¶∂ ∆ËÏ.: 210 7211845 º·Í: 210 7215082 E-mail: info@epsyype.gr Website: www.epsyype.gr

28 √ÎÙˆ‚Ú›Ô˘ 2 ¡ÔÂÌ‚Ú›Ô˘ 2006

18th International Congress on Pediatrics Contact: Dr Gh. Valizadeh Tel.: 98 2 166 428 998 Fax: 98 2 166 923 054 E-mail: pedcong@tums.ac.ir

Tehran, Iran