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Marmara Medical Journal 

Marmara Üniversitesi Tıp Fakültesi Dergisi 

Editör 

Prof. Dr. Mithat Erenus 

Koordinatörler 

Seza Arbay, MA 

Dr. Vera Bulgurlu 

Editörler Kurulu 

Prof. Dr. Mehmet Ağırbaşlı 

Prof. Dr. Serpil Bilsel 

Prof. Dr. Safiye Çavdar 

Prof. Dr. Tolga Dağlı 

Prof. Dr. Haner Direskeneli 

Prof. Dr. Kaya Emerk 

Prof. Dr. Mithat Erenus 

Prof. Dr. Zeynep Eti 

Prof. Dr. RainerVV. Guillery 

Prof. Dr. Oya Gürbüz 

Prof. Dr. Hande Harmancı 

Prof. Dr. Hızır Kurtel 

Prof. Dr. Ayşe Özer 

Prof. Dr. Tülin Tanrıdağ 

Prof. Dr. Tufan Tarcan 

Prof. Dr. Cihangir Tetik 

Prof. Dr. Ferruh Şimşek 

Prof. Dr. Dr. Ayşegül Yağcı 

Prof. Dr. Berrak Yeğen 

Doç. Dr. İpek Akman 

Doç. Dr. Gül Başaran 

Doç. Dr. Hasan Batırel 

Doç. Dr. Nural Bekiroğlu 

Doç. Dr. Şule Çetinel 

Doç. Dr. Mustafa Çetiner 

Doç. Dr. Arzu Denizbaşı 

Doç. Dr. Gazanfer Ekinci 

Doç. Dr. Dilek Gogas 

Doç. Dr. Sibel Kalaça 

Doç. Dr. Atila Karaalp 

Doç. Dr. Bülent Karadağ 

Doç. Dr. Handan Kaya 

Doç. Dr. Gürsu Kıyan 

Doç. Dr. Şule Yavuz 

Asist. Dr. Asım Cingi 

Asist. Dr. Arzu Uzuner


Marmara Üniversitesi T p Fakültesi Dergisi 

DERGİ HAKKINDA 

Marmara Medical Journal, Marmara Üniversitesi Tıp Fakültesi tarafından 

yayımlanan multidisipliner ulusal ve uluslararası tüm tıbbi kurum ve personele 

ulaşmayı hedefleyen bilimsel bir dergidir. Marmara Üniversitesi Tıp Fakültesi 

Dergisi, tıbbın her alanını içeren özgün klinik ve deneysel çalışmaları, ilginç olgu 

bildirimlerini, derlemeleri, davet edilmiş derlemeleri, Editöre mektupları, 

toplantı, haber ve duyuruları, klinik haberleri ve ilginç araştırmaların özetlerini , 

ayırıcı tanı, tanınız nedir başlıklı olgu sunumlarını, , ilginç, fotoğraflı soru-cevap 

yazıları (photo-quiz) ,toplantı, haber ve duyuruları, klinik haberleri ve tıp 

gündemini belirleyen güncel konuları yayınlar. 

Periyodu: Marmara Medical Journal -Marmara Üniversitesi Tıp Fakültesi Dergisi 

yılda 3 sayı olarak OCAK,MAYIS VE EKİM AYLARINDA yayınlanmaktadır. 

Yayına başlama tarihi:1988 

2004 Yılından itibaren yanlızca elektronik olarak 

yayınlanmaktadır 

Yayın Dili: Türkçe, İngilizce 

eISSN: 1309-9469 

Temel Hedef Kitlesi: Tıp alanında tüm branşlardaki hekimler, uzman ve öğretim 

üyeleri, tıp öğrencileri 

İndekslendiği dizinler: EMBASE - Excerpta Medica ,TUBITAK - Türkiye Bilimsel 

ve Teknik Araştırma Kurumu , Türk Sağlık Bilimleri İndeksi, Turk Medline,Türkiye 

Makaleler Bibliyografyası ,DOAJ (Directory of Open Access Journals) 

Makalelerin ortalama değerlendirme süresi: 8 haftadır 

Makale takibi -iletişim 

Seza Arbay 

Marmara Medical Journal (Marmara Üniversitesi Tıp Fakültesi Dergisi) 

Marmara Üniversitesi Tıp Fakültesi Dekanlığı, 

Tıbbiye cad No:.49 Haydarpaşa 34668, İSTANBUL 

Tel: +90 0 216 4144734 

Faks: +90 O 216 4144731 

e-posta: mmj@marmara.edu.tr 

Yayıncı 

Plexus BilişimTeknolojileri A.Ş. 

Tahran Caddesi. No:6/8, Kavaklıdere, Ankara 

Tel: +90 0 312 4272608 

Faks: +90 0312 4272602 

Yayın Hakları: Marmara Medical Journal ‘in basılı ve web ortamında yayınlanan yazı, resim, 

şekil, tablo ve uygulamalar yazılı izin alınmadan kısmen veya tamamen herhangi bir vasıtayla 

basılamaz. Bilimsel amaçlarla kaynak göstermek kaydıyla özetleme ve alıntı yapılabilir. 

www.marmaramedicaljournal.org


Marmara Üniversitesi Tıp Fakültesi Dergisi 

YAZARLARA BİLGİ 

Marmara Medical Journal – Marmara 

Üniversitesi Tıp Fakültesi Dergisine ilginize 

teşekkür ederiz. 

Derginin elektronik ortamdaki yayınına 

erişim www.marmaramedicaljournal.org 

adresinden serbesttir. 

Marmara Medical Journal tıbbın 

klinik ve deneysel alanlarında özgün 

araştırmalar, olgu sunumları, derlemeler, 

davet edilmiş derlemeler, mektuplar, ilginç, 

fotoğraflı soru-cevap yazıları (photo-quiz), 

editöre mektup , toplantı, haber ve 

duyuruları, klinik haberleri ve ilginç 

araştırmaların özetlerini yayınlamaktadır. 

Yılda 3 sayı olarak Ocak, Mayıs ve Ekim 

aylarında yayınlanan Marmara Medical 

Journal hakemli ve multidisipliner bir 

dergidir.Gönderilen yazılar Türkçe veya 

İngilizce olabilir. 

Değerlendirme süreci 

Dergiye gönderilen yazılar, ilk olarak 

dergi standartları açısından incelenir. Derginin 

istediği forma uymayan yazılar, daha ileri bir 

incelemeye gerek görülmeksizin yazarlarına 

iade edilir. Zaman ve emek kaybına yol 

açılmaması için, yazarlar dergi kurallarını 

dikkatli incelemeleri önerilir. 

Dergi kurallarına uygunluğuna karar 

verilen yazılar Editörler Kurulu tarafından 

incelenir ve en az biri başka kurumdan olmak 

üzere iki ya da daha fazla hakeme gönderilir. 

Editör, Kurulu yazıyı reddetme ya da 

yazara(lara) ek değişiklikler için gönderme 

veya yazarları bilgilendirerek kısaltma 

yapmak hakkına sahiptir. Yazarlardan 

istenen değişiklik ve düzeltmeler yapılana 

kadar, yazılar yayın programına 

alınmamaktadır. 

Marmara Medical Journal gönderilen 

yazıları sadece online olarak 

http://marmaramedicaljournal.org/submit. 

adresinden kabul etmektedir. 

Yazıların bilimsel sorumluluğu yazarlara 

aittir. Marmara Medical Journal yazıların 

bilimsel sorumluluğunu kabul etmez. Makale 

yayına kabul edildiği takdirde Yayın Hakkı 

Devir Formu imzalanıp dergiye iletilmelidir. 

Gönderilen yazıların dergide yayınlanabilmesi 

için daha önce başka bir bilimsel yayın 

organında yayınlanmamış olması gerekir. 

Daha önce sözlü ya da poster olarak 

sunulmuş çalışmalar, yazının başlık 

sayfasında tarihi ve yeri ile birlikte 

belirtilmelidir. Yayınlanması için başvuruda 

bulunulan makalelerin, adı geçen tüm 

yazarlar tarafından onaylanmış olması ve 

çalışmanın başka bir yerde yayınlanmamış 

olması ya da yayınlanmak üzere 

değerlendirmede olmaması gerekmektedir. 

Yazının son halinin bütün yazarlar tarafından 

onaylandığı ve çalışmanın yürtüldüğü kurum 

sorumluları tarafından onaylandığı 

belirtilmelidir.Yazarlar tarafından imzalanarak 

onaylanan üst yazıda ayrıca tüm yazarların 

makale ile ilgili bilimsel katkı ve 

sorumlulukları yer almalı, çalışma ile ilgili 

herhangi bir mali ya da diğer çıkar çatışması 

var ise bildirilmelidir.( * ) 

( * ) Orijinal araştırma makalesi veya vaka 

sunumu ile başvuran yazarlar için üst yazı 

örneği: 

"Marmara Medical Journal'de yayımlanmak 

üzere sunduğum (sunduğumuz) "…-" başlıklı 

makale, çalışmanın yapıldığı 

laboratuvar/kurum yetkilileri tarafından 

onaylanmıştır. Bu çalışma daha önce başka 

bir dergide yayımlanmamıştır (400 sözcük – 

ya da daha az – özet şekli hariç) veya 

yayınlanmak üzere başka bir dergide 

değerlendirmede bulunmamaktadır. 

Yazıların hazırlanması 

Derginin yayın dili İngilizce veya 

Türkçe’dir. Türkçe yazılarda Türk Dil Kurumu 

Türkçe Sözlüğü (http://tdk.org.tr) esas 

alınmalıdır. Anatomik terimlerin ve diğer tıp 

terimlerinin adları Latince olmalıdır. 

Gönderilen yazılar, yazım kuralları açısından 

Uluslararası Tıp Editörleri Komitesi tarafından 

hazırlanan “Biomedikal Dergilere Gönderilen 

Makalelerde Bulunması Gereken Standartlar “ 

a ( Uniform Requirements For Manuscripts 

Submittted to Biomedical Journals ) uygun 

olarak hazırlanmalıdır. 

(http://www. ulakbim.gov.tr /cabim/vt) 

Makale içinde kullanılan kısaltmalar 

Uluslararası kabul edilen şeklide olmalıdır 

(http..//www.journals.tubitak.gov.tr/kitap/ma 


knasyaz/) kaynağına başvurulabilir. 

Birimler, Ağırlıklar ve Ölçüler 11. Genel 

Konferansı'nda kabul edildiği şekilde 

Uluslararası Sistem (SI) ile uyumlu olmalıdır. 

Makaleler Word, WordPerfect, EPS, 

LaTeX, text, Postscript veya RTF formatında 

hazırlanmalı, şekil ve fotoğraflar ayrı dosyalar 

halinde TIFF, GIF, JPG, BMP, Postscript, veya 

EPS formatında kabul edilmektedir. 

Yazı kategorileri 

Yazının gönderildiği metin dosyasının 

içinde sırasıyla, Türkçe başlık, özet, anahtar 

sözcükler, İngilizce başlık, özet, İngilizce 

anahtar sözcükler, makalenin metini, 

kaynaklar, her sayfaya bir tablo olmak üzere 

tablolar ve son sayfada şekillerin (varsa) alt 

yazıları şeklinde olmalıdır. Metin dosyanızın 

içinde, yazar isimleri ve kurumlara ait bilgi, 

makalede kullanılan şekil ve resimler 

olmamalıdır. 

Özgün Araştırma Makaleleri 

Türkçe ve İngilizce özetler yazı başlığı 

ile birlikte verilmelidir. 

(i)özetler: Amaç (Objectives), Gereç ve 

Yöntem (Materials and Methods) ya da 

Hastalar ve Yöntemler (Patients and 

Methods), Bulgular (Results) ve Sonuç 

(Conclusion) bölümlerine ayrılmalı ve 200 

sözcüğü geçmemelidir. 

(ii) Anahtar Sözcükler Index Medicus 

Medical Subject Headings (MeSH) ‘e uygun 

seçilmelidir. 

Yazının diğer bölümleri, (iii) Giriş, (iv) 

Gereç ve Yöntem / Hastalar ve 

Yöntemler, (v) Bulgular, (vi) Tartışma ve 

(vii) Kaynaklar'dır. Başlık sayfası dışında 

yazının hiçbir bölümünün ayrı sayfalarda 

başlatılması zorunluluğu yoktur. 

Maddi kaynak , çalışmayı destekleyen 

burslar, kuruluşlar, fonlar, metnin sonunda 

teşekkürler kısmında belirtilmelidir. 

Olgu sunumları 

İngilizce ve Türkçe özetleri kısa ve tek 

paragraflık olmalıdır. Olgu sunumu özetleri 

ağırlıklı olarak mutlaka olgu hakkında bilgileri 

içermektedir. Anahtar sözcüklerinden sonra 

giriş, olgu(lar) tartışma ve kaynaklar şeklinde 

düzenlenmelidir. 

Derleme yazıları 

İngilizce ve Türkçe başlık, İngilizce ve 

Türkçe özet ve İngilizce ve Türkçe anahtar 

kelimeler yer almalıdır. Kaynak sayısı 50 ile 

sınırlanması önerilmektedir. 

Kaynaklar 

Kaynaklar yazıda kullanılış sırasına göre 

numaralanmalıdır. Kaynaklarda verilen 

makale yazarlarının sayısı 6 dan fazla ise ilk 

3 yazar belirtilmeli ve İngilizce kaynaklarda 

ilk 3 yazar isminden sonra “ et al.”, Türkçe 

kaynaklarda ise ilk 3 yazar isminden sonra “ 

ve ark. “ ibaresi kullanılmalıdır. 

Noktalamalara birden çok yazarlı bir 

çalışmayı tek yazar adıyla kısaltmamaya ve 

kaynak sayfalarının başlangıç ve bitimlerinin 

belirtilmesine dikkat edilmelidir. Kaynaklarda 

verilen dergi isimleri Index Medicus'a 

(http://www.ncbi.nim.nih.gov/sites/entrez/qu 

ery.fcgi?db=nlmcatalog) veya Ulakbim/Türk 

Tıp Dizini’ne uygun olarak kısaltılmalıdır. 

Makale: Tuna H, Avcı Ş, Tükenmez Ö, 

Kokino S. İnmeli olguların sublukse 

omuzlarında kas-sinir elektrik uyarımının 

etkinliği. Trakya Univ Tıp Fak Derg 

2005;22:70-5. 

Kitap: Norman IJ, Redfern SJ, (editors). 

Mental health care for elderly people. New 

York: Churchill Livingstone, 1996. 

Kitaptan Bölüm: Phillips SJ, Whisnant JP 

Hypertension and stroke. In: Laragh JH, 

Brenner BM, editors. Hypertension: 

Pathophysiology, Diagnosis, and 

Management. 2nd ed. New York: Raven Pres, 

1995:465-78. 

Kaynak web sitesi ise: Kaynak 

makalerdeki gibi istenilen bilgiler verildikten 

sonra erişim olarak web sitesi adresi ve 

erişim tarihi bildirilmelidir. 

Kaynak internet ortamında basılan 

bir dergi ise: Kaynak makaledeki gibi 

istenilen bilgiler verildikten sonra erişim 

olarak URL adresi ve erişim tarihi verilmelidir. 

Kongre Bildirileri: Bengtsson S, 

Solheim BG. Enforcement of data protection, 

privacy and security in medical informatics. 

In: Lun KC, Degoulet P, Piemme TE, Rienhoff 

O, editors. MEDINFO 92. Proceedings of the 

7th World Congress on Medical Informatics; 

1992 Sep 6-10; Geneva, Switzerland. 

Amsterdam: North-Holland; 1992:1561-5. 

Tablo, şekil, grafik ve fotoğraf 

Tablo, şekil grafik ve fotoğraflar yazının 

içine yerleştirilmiş halde gönderilmemeli. 

Tablolar, her sayfaya bir tablo olmak üzere 

yazının gönderildiği dosya içinde olmalı ancak 

yazıya ait şekil, grafik ve fotografların her biri 

ayrı bir imaj dosyası (jpeg yada gif) olarak 

gönderilmelidir. 


Tablo başlıkları ve şekil altyazıları eksik 

bırakılmamalıdır. Şekillere ait açıklamalar 

yazının gönderildiği dosyanın en sonuna 

yazılmalıdır. Tablo, şekil ve grafiklerin 

numaralanarak yazı içinde yerleri 

belirtilmelidir. Tablolar yazı içindeki bilginin 

tekrarı olmamalıdır. 

Makale yazarlarının, makalede eğer daha 

önce yayınlanmış alıntı yazı, tablo, şekil, 

grafik, resim vb var ise yayın hakkı sahibi ve 

yazarlardan yazılı izin almaları ve makale üst 

yazısına ekleyerek dergiye ulaştırmaları 

gerekmektedir. 

Tablolar Metin içinde atıfta bulunulan 

sıraya göre romen rakkamı ile 

numaralanmalıdır. Her tablo ayrı bir sayfaya 

ve tablonun üst kısmına kısa ancak anlaşılır 

bir başlık verilerek hazırlanmalıdır. Başlık ve 

dipnot açıklayıcı olmalıdır. 

Sütun başlıkları kısa ve ölçüm değerleri 

parantez içinde verilmelidir. Bütün 

kısaltmalar ve semboller dipnotta 

açıklanmalıdır. Dipnotlarda şu semboller: 

(†‡§) ve P değerleri için ise *, **, *** 

kullanılmalıdır. 

SD veya SEM gibi istatistiksel değerler 

tablo veya şekildin altında not olarak 

belirtilmelidir. 

Grafik, fotoğraf ve çizimler ŞEKİL olarak 

adlandırılmalı, makalede geçtiği sıraya gore 

numaralanmalı ve açıklamaları şekil altına 

yazılmalıdır Şekil alt yazıları, ayrıca metinin 

son sayfasına da eklenmelidir. Büyütmeler, 

şekilde uzunluk birimi (bar çubuğu içinde) ile 

belirtilmelidir. Mikroskopik resimlerde 

büyütme oranı ve boyama tekniği 

açıklanmalıdır. 

Etik 

Marmara Medical Journal’a yayınlanması 

amacı ile gönderilen yazılar Helsinki 

Bildirgesi, İyi Klinik Uygulamalar Kılavuzu,İyi 

Laboratuar Uygulamaları Kılavuzu esaslarına 

uymalıdır. Gerek insanlar gerekse hayvanlar 

açısından etik koşullara uygun olmayan 

yazılar yayınlanmak üzere kabul edilemez. 

Marmara Medical Journal, insanlar üzerinde 

yapılan araştırmaların önceden Araştırma Etik 

Kurulu tarafından onayının alınması şartını 

arar. Yazarlardan, yazının detaylarını ve 

tarihini bildirecek şekilde imzalı bir beyan ile 

başvurmaları istenir. 

Çalışmalar deney hayvanı kullanımını 

içeriyorsa, hayvan bakımı ve kullanımında 

yapılan işlemler yazı içinde kısaca 

tanımlanmalıdır. Deney hayvanlarında özel 

derişimlerde ilaç kullanıldıysa, yazar bu 

derişimin kullanılma mantığını belirtmelidir. 

İnsanlar üzerinde yapılan deneysel 

çalışmaların sonuçlarını bildiren yazılarda, 

Kurumsal Etik Kurul onayı alındığını ve bu 

çalışmanın yapıldığı gönüllü ya da hastalara 

uygulanacak prosedürlerin özelliği tümüyle 

kendilerine anlatıldıktan sonra, onaylarının 

alındığını gösterir cümleler yer almalıdır. 

Yazarlar, bu tür bir çalışma söz konusu 

olduğunda, uluslararası alanda kabul edilen 

kılavuzlara ve TC. Sağlık Bakanlığı tarafından 

getirilen ve 28 Aralık 2008 tarih ve 27089 

sayılı Resmi Gazete'de yayınlanan "Klinik 

araştırmaları Hakkında Yönetmelik" ve daha 

sonra yayınlanan 11 Mart 2010 tarihli resmi 

gazete ve 25518 sayılı “Klinik Araştırmalar 

Hakkında Yönetmelikte Değişiklik Yapıldığına 

Dair Yönetmelik” hükümlerine uyulduğunu 

belirtmeli ve kurumdan aldıkları Etik Komitesi 

onayını göndermelidir. Hayvanlar üzerinde 

yapılan çalışmalar için de gereken izin 

alınmalı; yazıda deneklere ağrı, acı ve 

rahatsızlık verilmemesi için neler yapıldığı 

açık bir şekilde belirtilmelidir. 

Hasta kimliğini tanıtacak fotoğraf 

kullanıldığında, hastanın yazılı onayı 

gönderilmelidir. 

Yazı takip ve sorularınız için iletişim: 

Seza Arbay 

Marmara Universitesi Tıp Fakültesi 

Dekanlığı, 

Tıbbiye Caddesi, No: 49, Haydarpaşa 

34668, İstanbul 

Tel:+90 0 216 4144734 

Faks:+90 0 216 4144731 

e-posta: mmj@marmara.edu.tr 


İÇİNDEKİLER 

Orjinal Araştırma 

THE INCIDENCE OF LOW BIRTH WEIGHT IN 5000 LIVEBORN INFANTS AND THE 

ETIOLOGY OF FETAL RISK FACTORS 

Emel Altuncu, Sultan Kavuncuoğlu, Pınar Özdemir Gökmirza, Zeynel Albayrak, Ayfer Arduç…….…46 

THE ROLE OF VAGINAL MATURATION VALUE ASSESSMENT IN PREDICTION OF 

VAGINAL PH, SERUM FSH AND E 2 LEVELS 

Pınar Yörük, Meltem Uygur, Mithat Erenus, Funda Eren……………………………………..…………...52 

RELATIONSHIP BETWEEN ELEVATED SERUM CRP LEVEL AND DIABETES 

MELLITUS IN ACUTE MYOCARDIAL INFARCTION 

Kenan Topal, Sunay Sandıkçı, Hakan Demirhindi, Ersin Akpınar, Esra Saatçı………………………....58 

SOCIAL ISOLATION STRESS IN THE EARLY LIFE REDUCES THE SEVERITY OF 

COLONIC INFLAMMATION 

Sevgin Özlem İşeri, Fatma Tavsu, Beyhan Sağlam, Feriha Ercan, Nursal Gedik, Berrak C. Yeğen.....65 

Olgu Sunumu 

LAPAROSCOPIC APPROACH FOR EPIPHRENIC ESOPHAGEAL DIVERTICULA 

Osman Kurukahvecioğlu, Ekmel Tezel, Bahadır Ege, Hande Köksal, Emin Ersoy……………..….……73 

NEONATAL MIXED SEX-CORD STROMAL TUMOR OF THE TESTIS: A CASE REPORT 

Asıf Yıldırım, Erem Başok, Adnan Başaran, Ebru Zemheri, Reşit Tokuç…….…………………………...77 

SECONDARY MALIGNANCIES AFTER LYMPHOMA TREATED BY RADIOTHERAPY- 

CASE REPORT 

Alper Çelik, Suat Kutun, Turgay Fen, Gülay Bilir, Akın Önder, Abdullah Çetin…………....…………..80 

TWO NEW KABUKI CASES OF KABUKI MAKE-UP SYNDROME 

Ahmet Sert, Mehmet Emre Atabek, Özgür Pirgon……………………………………………………...........86 

Derleme 

IS THERE A “HIDDEN HIV/AIDS EPIDEMIC” IN TURKEY?: THE GAP BETWEEN THE 

NUMBERS AND THE FACTS 

Pınar Ay, Selma Karabey………………………………………………………………………...……………...90 

MAGNETIC RESONANCE IMAGING AND ANESTHESIA 

Berrin Işık……………………………………………………………………………………………………….…98

ORIGINAL RESEARCH 

THE INCIDENCE OF LOW BIRTH WEIGHT IN 5000 LIVEBORN INFANTS AND THE 

ETIOLOGY OF FETAL RISK FACTORS 

Emel Altuncu, Sultan Kavuncuoğlu, Pınar Özdemir Gökmirza, Zeynel Albayrak, Ayfer Arduç 

Ministry of Health,Istanbul Bakırköy Maternity and Children Teaching Hospital, Department of Pediatrics, 

Istanbul, Türkiye. 

ABSTRACT 

Objective: To identify the low birth weight (LBW) incidence in 5000 live born babies in the Bakirkoy 

Maternity and Children Teaching Hospital. 

Material and Methods: LBW was defined as infant weight below 2500g and these infants constituted the 

study group. Babies with normal birth weight (NBW) chosen randomly in equal numbers from 5000 live 

born babies formed the control group. Presentation, route of delivery, congenital anomaly, multiple births 

and the sex of the infants were also recorded. 

Results: In the 5000 live born babies, incidence of LBW was 9.14%. The incidence of preterm and full term 

was 5.7% and 3.4%, respectively. Of the LBW infants, 62.8% were preterm, 37.2% were full term. The rate 

of multiple gestations was found to be 13.9% in LBW infants and 0.8% in NBW infants. Excluding multiple 

gestations, 46.4% of the babies in the LBW group were female, and 53.6% were male. In the NBW group, 

the rates were 46.3% and 53.7% respectively. Abdominal delivery was seen in 32.3% of the LBW infants 

and 21.6% in the NBW infants. The rate of breech presentation was higher in the LBW (5.1%) than in the 

NBW infants (1.3%). The incidence of congenital anomaly was 6.2% in the LBW group and 3.3% in the 

NBW group. 

Conclusion: The sex of the infant did not have any influence on the birth weight; however, multiple 

gestation and congenital anomaly were important factors. Additionally, abdominal delivery and non-vertex 

presentations were observed more frequently in the LBW infants. 

Keywords: Low birth weight, Incidence, Aetiology 

5000 CANLI DOĞUMDA DÜŞÜK DOĞUM AĞIRLIKLI BEBEK ORANI VE 

ETYOLOJİDEKİ FETAL RİSK FAKTÖRLERİ 

ÖZET 

Amaç: Hastanemizde gerçekleşen 5000 canlı doğumdaki düşük doğum ağırlıklı (DDA) bebek oranını 

belirlemek amaçlandı. 

Gereç ve Yöntem: Doğum ağırlığı 2500g altında olan bebekler düşük doğum ağırlıklı olarak tanımlandı ve 

çalışma grubunu oluşturdu. 5000 canlı doğum içinden basit rastgele yöntemle seçilen, DDA bebeklerle aynı 

sayıda normal doğum ağırlıklı (NDA) bebek alınarak kontrol grubu oluşturuldu. Tüm bebekler için cinsiyet, 

doğum şekli, çoğul gebelikler ve konjenital anomali varlığı öğrenildi. 

Bulgular: Beşbin canlı doğumda DDA sıklığı %9.14, term ve preterm DDA bebeklerin sıklığı ise sırasıyla 

%5.7 ve %3.4 idi. DDA bebeklerin %62.8'i preterm, %37.2'si term bulundu. Çoğul gebelik sıklığının DDA 

bebeklerde %13.9 ve NDA bebeklerde %0.8 olduğu görüldü. Çoğul gebelikler dışlandıktan sonra iki grup 

karşılaştırıldı. DDA bebeklerin %46.4'i kız, %53.6'si erkek, NDA bebeklerin %46.3'ü kız ve %53.7'sı 

erkekti. Sezeryanla doğum DDA bebeklerde (%32.3), NDA bebeklerden (%21.6) daha fazlaydı. Benzer 

şekilde, makat doğum DDA bebeklerde daha sık görüldü (sırasıyla %5.1 ve %1.3). Konjenital anomali 

sıklığı DDA bebeklerde %6.2 iken, bu oran NDA bebeklere %3.3 olarak bulundu. 

Sonuç: Bebeğin cinsiyetinin doğum ağırlığına etkisi görülmezken, çoğul gebelik ve konjenital anomali 

varlığı doğum ağırlığını etkilemekteydi. Ayrıca, DDA bebeklerde sezeryanla doğum ve baş geliş dışındaki 

prezentasyonlar daha sık görülmekteydi. 

Anahtar Kelimeler: Düşük doğum ağırlığı, Sıklık, Etyoloji 

İletişim Bilgileri: 

Emel Altuncu 

e-mail: emelkayrak@yahoo.com 

SB. Istanbul Bakırköy Maternity and Children Teaching 

Hospital,Department of Pediatrics, Istanbul, Turkey 

Marmara Medical Journal 2006;19(2);46-51 

46


Emel Altuncu, et al. 

The incidence of low birth weight in 5000 liveborn infants and the etiology of fetal risk factors 

INTRODUCTION 

Low birth weight (LBW) is responsible for 60% 

of the infant mortality in the first year of life and 

it carries a 40-fold increase in the risk of neonatal 

mortality during the first month 1-4 . Since birth 

weight has a strong correlation with infant 

survival, attentions have been given to strategies 

that will reduce the proportion of infants with 

LBW. With recent advances in modern obstetric 

and neonatal care and technological development, 

high risk neonates have a greater chance of 

survival in the newly formed intensive care units. 

This also causes an increase in the rate of LBW 

infants, and subsequently an increased rate of 

long-term neurological sequelae. 

The World Health Organization has estimated that 

annually 24 million LBW infants are born in 

developing countries. As the prevalence of LBW 

infants is around 5% in many industrialized 

countries, it changes between 5-30% in 

underdeveloped or developing countries 3,5-12 . If 

we take into account that, millions of LBW 

infants are born annually in the World, we need 

to begin researching the health of neonates 

starting with birth weight. In this prospective 

study, we aimed to identify the LBW incidence in 

5000 live born babies in our hospital and the 

associated risk factors of LBW related to the 

infant. We also aimed to evaluate the rate of 

infants who were small for gestational age 

(SGA), rate of preterm delivery, their sex 

distribution, route of delivery, presentation, 

incidence of multiple gestations and congenital 

anomalies. 

METHODS 

In this prospective cross-sectional study, 5000 live 

born babies were evaluated randomly between 

October 2000-May 2001 in the Bakirköy 

Maternity and Children’s Hospital in Istanbul. 

Aborted babies and stillbirths were excluded 

because of difficulties in accurately defining 

gestational age. The infants were weighed on an 

electronic metric scale in the delivery room 

immediately after birth. 

LBW was defined as infant weight below 

2500g and these infants constituted the study 

group. Since the accurate date of the last 

menstrual period was not known in about one 

third of the mother and due to failing routines 

in the maternity ward, the gestational age was 

estimated by Ballard scoring performed in the 

first 24 hours after delivery. Babies born 

before 37 completed gestational weeks were 

defined as preterm. The neonates were 

examined and all anthropometric 

measurements were obtained at the same 

time. A baby was classified as SGA if the 

birth weight fell below the 10th percentile for 

gestational age, based on Lubchencho curves. 

The sex of the infants, presentation, route of 

delivery, congenital anomaly and multiple 

births were recorded on prepared forms. A 

history of congenital anomaly in the family 

was also obtained. Babies with normal birth 

weight (NBW) (≥2500g) chosen randomly in 

equal numbers from 5000 live born babies 

formed the control group and the same 

parameters were evaluated for this group. 

We used Chi Square and Mantel-Haenszel 

tests for statistical analysis. Statistical 

significance in this study was defined as 

p




statistically significant difference was found when 

comparing the sex of the babies in the two groups 

(x 2 =0.01, p=0.97). 

Mode of delivery was compared between the two 

groups. Delivery by way of caesarean section was 

seen in 32.3% of the LBW group and this rate was 

21.6% in the NBW group (Table I). The 

difference was statistically significant (x 2 =11.63, 

p=0.001). The indications for abdominal delivery 

are in Table II. Elective abdominal deliveries were 

more frequent in the NBW infants but the 

preference for caeserean section was based more 

commonly on perinatal problems among the LBW 

births. 

Table I: Characteristics of LBW and NBW infants 

LBW 

NBW 

The mean gestational age (w) 35.8 ±2.5 38.1 ± 0.6 

The mean birth weight (g) 2037.7 ± 430.6 3352.1 ± 401.8 

Multiple gestation (%) 13.9 0.8 

Female (%) 46.4 46.3 

Male (%) 53.6 53.7 

Caesarean section (%) 32.3 21.6 

Non-vertex presentation (%) 6.5 1.3 

Congenital anomalies (%) 6.2 3.3 

Table II: The indications for abdominal delivery in LBW and NBW infants 

Indications 

LBW 

NBW 

n:353 % n:453 % 

Fetal distress 31 8 31 7 

Elective C/S 28 8 47 10 

IUGR/LGA 12 3 4 1 

Preeclampsia 11 3 2 0.4 

Abruptio placenta 7 2 4 1 

Oligohydroamniosis 9 2 - - 

Non-vertex presentation 6 2 2 2 

Placenta previa 2 1 4 1 

Premature rupture of membranes 5 1 1 0.2 

Cord presentation 1 0.3 2 0.4 

Fetal anomaly 2 0.5 1 0.2 

Maternal hyperthyroidism - - 1 0.2 

48




The rate of breech presentation was higher in the 

LBW (5.1%) than in the NBW infants (1.3%). 

1.4% of the LBW infants were born by 

incomplete breech presentation, but there were no 

babies born by incomplete breech presentation 

among the NBW infants (Table I). LBW was 

associated with increased rate of non-vertex 

presentations (x 2 =16.46, p=0.000). 

In this study, congenital anomalies of the study 

and the control groups were evaluated (Table III). 

The incidence was 6.2% in the LBW group and 

3.3% in the NBW group (Table I). The difference 

between the two groups was important (x 2 =3.86, 

p=0.04). Among the LBW newborns having 

isolated or multiple congenital malformations, 

2.5% were SGA and 3.7% were premature. The 

incidence of congenital malformations in all SGA 

babies was 5.8%. In our preterm population, the 

malformation incidence was 6.5%, but 54% of the 

preterm infants with congenital anomalies were 

preterm SGA babies. 72% of the LBW infants 

with congenital anomalies were full term or 

preterm SGA. A family history of congenital 

anomalies was seen in 2.8% of the LBW infants 

and in 2.4% of the NBW babies. There was no 

important difference statistically (x 2 =0.12, 

p=0.72). Also, the effect of consanguinity 

between parents on birth weight was evaluated. 

7.5% of the cases had first-degree consanguinity 

between the mother and father in the LBW group 

and this rate was 7.8% in the NBW group. Second 

or higher degrees of consanguinity rates were 7% 

and 5%, respectively in both groups. This result 

did not create a statistically significant importance 

(x 2 =0.05, p=0.81). and consanguinity between 

parents was not found to be a risk factor in the 

aetiology of LBW. 

Table III: Congenital anomalies of LBW and NBW infants 

LBW 

NBW 

Isolated defects 

Congenital hip dislocation 6 2 

(+ Pes equinovarus) 3 - 

Sacral sinus 2 4 

Myeloschisis 1 - 

Hypospadias 3 1 

Cryptorchidism 1 1 

Inguinal hernia - 1 

Ambiguous genitale 2 - 

Anal atresia/small intestine stenosis 1 1 

Cleft lip and palate 2 - 

Extremity anomalies 3 - 

Others (diastasis recti, hypotelorism, 1 4 

cleft uvula, penile mass) 

Multiple anomalies 

Down’s Syndrome - 1 

Ambiguous genitalia, hydrocephaly, vaginal 

atresia, anal atresia 1 - 

Myelomeningocele, hydrocephaly, extremity 

anomaly 1 - 

Atypical face, cyanotic congenital heart 

disease, limb anomaly 1 - 

Cleft lip and palate, microcephaly, atypical face, 

syndactylism 1 - 

49




DISCUSSION 

In this study, incidence of LBW infants was 

9.14% and this was similar to the literature 13 . 

Previous studies have reported similar results, for 

example, the LBW rates in two different studies in 

Turkey were 8.7% and 10%, respectively 14,15 . In 

many developed countries, LBW rates are around 

5% 12 . The rate of LBW in our study was similar 

to rates reported in developed countries. The 

similarity to developed countries can be based 

upon the contribution of only live born neonates. 

The perinatal mortality (34.9‰) is very high in 

our country and a great number of LBW and very 

LBW infants are lost during parturition 4 . So this 

leads to misinterpretation of the outcome. 

Although multiple gestations represented only 

2.09% of the live births, they account for a 

disproportionately large share of adverse 

pregnancy outcomes. With the development of 

obstetrical approaches, the incidence of multiple 

gestations began to increase. The risk of giving 

birth to a LBW infant increased significantly in 

multiple gestations in our study and 80% of 

multiple gestations resulted in preterm birth. 

Studies dealing with the aetiology of LBW have 

shown us that, female sex is an important risk 

factor and this is attributed to the predisposition of 

the female sex to the other risk factors 6,16,17 . In 

our study, the rate of male and female sex among 

LBW infants was similar and this led us to 

conclude that the sex of the infant did not affect 

the weight of the baby. 

Other important results were the significant 

differences in the method of delivery and the 

presentations of neonates between the LBW and 

NBW groups. The rate of caesarean section was 

much higher in the LBW births (32.3%) than in 

the NBW births (21.6%). Delivery by way of 

caesarean section was seen more frequently in 

LBW infants and this indicated once more that 

LBW infants were more prone to morbidity and 

mortality. 

The rate of cephalic presentation was 93.5% in the 

LBW group, but 98.7% in the NBW group. When 

compared with cephalic presentation, breech 

births were associated with an increased rate of 

LBW. Whereas, the overall incidence of breech 

presentation in deliveries is only 3% to 4%, for 

infants weighing less than 2500g at birth, the 

incidence may be 30% or greater. As compared 

with the NBW infants, birth trauma and umbilical 

cord prolapsus are seen more commonly in LBW 

and/or breech births. During labour, the umbilical 

cord passes the cervix before the head, so the 

umbilical cord is entrapped in between the cervix 

and head. After the beginning of compression, 

delay in labour increases hypoxia. With a LBW 

infant, the size of the head is even greater in 

relation to that of the buttocks and the chance of 

entrapment is markedly increased. This condition 

results in increased hypoxia and because it needs 

traction, it can cause trauma to the spinal cord and 

skeletal system. Goldenberg and Nelson found 

that, during labour, the premature fetus in breech 

presentation was 16 times more likely to die than 

the premature fetus in vertex presentation 18 . For 

these reasons, in LBW neonatesthe most rational 

method of delivery is caesarean section 19 . In view 

of this information it may be said that, 

identification of high-risk pregnancies and choice 

of appropriate method of delivery have been 

successfully achieved in our hospital parallel to 

the literature. 

Intrauterine growth retardation (IUGR) is a 

frequently reported outcome among infants with 

congenital malformations. The presence of IUGR 

may indicate an underlying structural abnormality 

or aetiologically it may predispose to defects 

rather than vice versa 20 . The rate of congenital 

malformations was 6.2% in the LBW group, 3.3% 

in the NBW group indicating a strong association 

between LBW and malformations. Among the 

LBW neonates with isolated or multiple 

congenital malformations, 2.5% were SGA and 

3.7% were premature. However, the incidence of 

congenital malformations in all SGA babies, was 

5.8%. In our preterm population, malformation 

incidence was 6.5%, but 54% of the preterm 

infants with congenital anomalies were preterm 

SGA babies. If we take full term and preterm 

SGA infants into consideration together, 72% of 

LBW infants with congenital anomalies were 

SGA. In a study reported in our hospital in 1999, 

congenital malformations was the fourth leading 

cause of death (11.4%) in perinatal mortality 

cases 4 . The significant role of congenital 

malformation in the aetiology of the LBW, 

especially for IUGR, causing an increase from 

3.3% to 8% in the risk of LBW indicates a need to 

check for malformations by performing antenatal 

ultrasonography more strictly in IUGR 

fetuses.Furthermore, it emphasızes the need for a 

higher number of more developed genetic 

laboratories. 

There was a limitation in this study. Because our 

study was performed in a maternity ward, if there 

were no symptoms or sings reflecting congenital 

infections, we did not check for congenital 

50




infections because of high cost. So we did not 

include the incidence of congenital infections in 

the aetiology of LBW. 

In summary, improving the community health 

should start with improving baby health, and 

developing new strategies to decrease the 

incidence of LBW infants should be the one of 

our first goals. A history of a LBW infant should 

be an indication to seek recurrent cases of low 

birth weight and to ensure that close monitoring of 

fetal growth is implemented in subsequent 

pregnancies. 

REFERENCES 

1. Papageorgion A, Bardin CL The extremely-lowbirth-weight 

infant. In:Avery GB,Fletcher MA, 

MacDonald MG, eds. Pathophysiology and 

Management of the Newborn. 

Philadelphia:Lippincott Williams&Wilkins, 

1999:445-472. 

2. Klaus MH, Fanaroff AA. Care of the high risk 

infant. Philadelphia:WB Saunders Company, 

1993:86-113. 

3. Wessel H, Cnattingius S, Bergstrom S, Dupret A, 

Reitmaier P. Maternal risk factors for preterm birth 

and low birth weight in Cape Verde. Acta Obstet 

Gynecol Scand 1996; 75: 36-46. 

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Çocuk Hastalıkları Egitim Hastanesi, Uzmanlık 

Tezi. Modifiye Wigglesworth sınıflaması ile 

perinatal mortalitenin 21659 dogumda 

degerlendirilmesi. 2000. 

5. Geary M, Rafferty G, Murphy JF. Comparison of 

live born and stillborn low birth weight and 

analysis of aetiological factors. Ir Med J 1997; 90: 

269-271. 

6. Wu S, Goldenberg RL. Intrauterine growth 

retardation and preterm delivery: Prenatal risk 

factors in an indigent population. Am J Obstet 

Gynecol 1990;162:213-218. 

7. Basso O, Olsen J, Christensen K. Low birth weight 

and prematurity in relation to paternal factors: a 

study of recurrence. Int J Epidemiology. 

1999;28:695-700. 

8. Raine T.The risk of repeating low birth weight and 

the role of prenatal care. Obstet and Gynecol 

1994;8:485-489. 

9. Mc Cormick MC. The contribution of low birth 

weight to infant mortality and childhood morbidity. 

N Engl J Med 1985; 312:82-90. 

10. Leung TN, Roach VJ, Lau TK. Incidence of 

preterm delivery in Hong Kong Chinese. Aust N Z 

J Obstet Gynaecol 1998;38: 138-141. 

11. Najmi RS. Distribution of birth weights of hospital 

born Pakistani infant. JPMA J Pak Med Assoc 

2000;50: 121-124. 

12. Low Birth weight. A tabulation of available 

information. Maternal Health and Safe Motherhood 

Programme. World Health Organization and 

UNICEF, Genova 1992. WTO/MCH/92.2. 

13. Can G, Çoban A,Oneş U,Özmen M, İnce Z. 

Yenidoğan ve hastalıkları. In: Neyzi O, Ertuğrul T, 

eds. Pediatri, 2nd ed. İstanbul: Nobel Tıp 

Yayınevleri, 1993;208-225. 

14. Arısoy AE, Sarman G. Chest and mid-arm 

circumferences in the identification of low birth 

weight infants. J Trop Pediatr 1995 ; 41: 34-47. 

15. Kayhan M, Argon S, Kırcalıoglu N. Anneye baglı 

düşük dogum agırlıgı nedenlerine ilişkin bir 

çalışma. Jinekoloji ve Obstetride Yeni Görüş ve 

Gelişmeler Dergisi 1991: 2: 21-25. 

16. Herceg A, Simpson JM, Thompson JF. Risk factors 

and outcomes associated with low birth weight 

delivery in the Australian Capital Territory 1989- 

90. J Paediatr Child Health. 1994; 30: 331-335. 

17. Steketee RW, Wirima JJ, Hightower AW, Slutsker 

L, Heymann DL, Breman JG. The effect of malaria 

and malaria prevention in pregnancy on offspring 

birth weight, prematurity and intrauterine growth 

retardation in rural Malawi. Am J Trop Med Hyg 

1996;55(1 Suppl):33-41. 

18. Goldenberg R, Nelson K. The premature breech. 

Am J Obstet Gynecol 1997;127.40. 

19. Salmancı N. Düşük Doğum tartılı bebekler. 

In:Dağoğlu T, ed. Neonatoloji, 1st ed. 

Istanbul:Nobel Tıp Kitapevleri, 2000;22:181-187. 

20. Khoury MJ, Erickson JD, Cordero JF, Mc Carthy 

BJ. Congenital malformations and intrauterine 

growth retardation: a population study. J Pediatr 

1988;82:83-90. 

51


THE ROLE OF VAGINAL MATURATION VALUE ASSESSMENT IN PREDICTION OF 

VAGINAL PH, SERUM FSH AND E 2 LEVELS 

Pınar Yörük 1 , Meltem Uygur 1 , Mithat Erenus 1 , Funda Eren 2 

1 Marmara University, Obstetrics and Gynecology, İstanbul, Türkiye 2 Marmara University, Pathology, 

İstanbul, Türkiye 

ABSTRACT 

Introduction: The objective of this study is to detect the correlation between vaginal maturation value (MV) 

and vaginal pH measurement, serum FSH and E 2 levels in women without vaginal infection. 

Materials And Methods: Fifty women with vasomotor symptoms were enrolled at the present study. All 

women underwent vaginal pH assessment, measurement of serum FSH and E 2 levels and vaginal MV 

measurement in addition to routine follow-up. For determination of vaginal MV, pap smear from lateral 

vaginal wall was obtained and evaluated. 

Results: In women with atrophic symptoms, the age and vaginal pH levels were significantly higher than 

women without these symptoms. Highly significant correlation between vaginal pH, vaginal MV and serum 

FSH was detected. Similarly highly significant inverse correlation was present between vaginal pH levels 

and vaginal MV. 

Discussion: In summary, this study confirms that vaginal pH and MV are similar to FSH in the identification 

of patients who have low estrogen levels or who are menopausal. Methods of deriving vaginal pH and MV 

are simple, practical, quick and economic. As a conclusion, the present study demonstrated that vaginal pH 

measurement and vaginal MV assessment is similar in diagnosis and monitoring of estrogen deficiency in 

women with urogenital atrophic symptoms. 

Keywords: vaginal maturation value, pH, menopause 

VAJİNAL PH, SERUM FSH VE E2 SEVİYELERİNİ ÖN GÖRMEDE VAJİNAL 

MATURASYON İNDEKSİNİN DEĞERİ 

ÖZET 

Giriş: Bu çalışmanın amacı vajinal enfeksiyonu olmayan kadınlarda vajinal maturasyon değeri (MV) ile 

vajinal pH, serum FSH ve E2 değerleri arasındaki korelasyonu saptamaktır. 

Materyal ve Metotlar: Vasomotor semptomları olan 50 kadın çalışmaya dahil edildi. Kadınlara rutin takibe 

ek olarak vajinal pH, vajinal MV, serum FSH ve E2 ölçümleri uygulandı. 

Sonuçlar: Atrofik semptomları olan kadınlarda yaş ve vajinal pH değerleri semptomu olmayan kadınlara 

oranla anlamlı olarak daha yüksek bulundu. Vajinal pH, vajinal MV ve serum FSH arasında kuvvetli bir 

korelasyon tespit edildi. Benzer şekilde, vajinal pH değerleriyle vajinal MV arasında da kuvvetli ters 

korelasyon gözlendi. 

Tartışma: Bu çalışmanın sonuçları menopozda olan veya düşük serum östrojeni olan kadınların ayırımında 

vajinal pH ve vajinal MV değerlerinin serum FSH ile benzer olduğunu doğrulamaktadır. Vajinal pH ve MV 

ölçümü basit, pratik,hızlı ve ekonomiktir. Vajinal pH ve vajinal MV ölçümünün ürogenital atrofik şikayetleri 

olan kadınlarda östrogen eksikliğinin tanısında ve takibinde benzer olduğu gösterilmiştir. 

Anahtar Kelimeler: vajinal maturasyon değeri, pH, menopoz 


Pınar Yörük 

e-mail: pinyoruk@yahoo.com 

Marmara University, Obstetrics and Gynecology, İstanbul, Türkiye 


52


Pınar Yörük, et al. 

The role of vaginal maturatıon value assessment in prediction of vaginal ph, serum fsh and E2 levels 

INTRODUCTION 

Menopause has great impacts on life-quality of all 

women and is defined as cessation of menstrual 

bleeding for at least 12 months, serum FSH value 

≥ 40 mIU/ml, and serum E 2 level < 20 pg/ml. It 

has been known for decades that without vaginal 

infections, vaginal pH is ≤ 4.5 during the 

reproductive years and > 4.5 before menarche and 

after menopause 1 . Only methods of deriving 

vaginal pH were not practical, and had low 

sensitivity and specificity due to contamination 

with cervical mucus, blood, or semen 2 . Vaginal 

maturation value (MV) of Meisels 3 calculated 

from the ratios of superficial, intermediate and 

parabasal cells in vaginal smears has been used to 

detect vaginal atrophy and estrogen deficiency in 

postmenopausal symptomatic women. MV is a 

useful marker to examine vaginal maturation and 

reveal vaginal estrogen deficiency regardless of 

the presence of inflammation 4 . After the 

introduction of vaginal pH device, it has been 

proposed that determination of vaginal pH in the 

absence of vaginitis in an outpatient setting might 

be a diagnostic feature of menopause. In this 

study we aimed to detect the correlation of vaginal 

MV with vaginal pH measurement, serum FSH 

and E 2 levels in women with climacteric 

symptoms. 

METHODS 

Study population: Fifty peri-postmenopausal 

otherwise healthy women attending to our 

menopause outpatient clinic with climacteric 

symptoms for the first time were enrolled at the 

present study. Demograpic characteristics 

including age, gravidy, parity and body mass 

index (BMI) and urogenital atrophic symptoms 

were questioned by the presence of vaginal 

dryness, dyspareunia, pruritus and dysuri. All 

women underwent vaginal pH assessment, 

measurement of serum FSH and E 2 levels and 

vaginal MV measurement in addition to routine 

follow-up. Amine test was carried out 

simultaneously with vaginal pH assessment in 

order to rule out vaginal infections and exclude 

false positive pH values. Women who have 

surgical menopause, systemic diseases, positive 

amine test, previous vaginal surgery involving 

more than 1/3 of the vagina, and women with 

history of current or past therapy of estrogenprogesteron 

replacement are excluded. 

Vaginal pH measurement: Vaginal pH levels are 

measured by Quickvue ® Advance pH and Amines 

Test, developed by Quidel ® Corporation (San 

Diego, USA). This device is composed of a foil 

wrapped test (contains nitrazine yellow for pH test 

and bromocresol green for amines test), and sterile 

amine controlled cotton swabs. Cotton swabs are 

applied to the lateral vaginal wall, then rubbed 

over the entire surface of the tests. Results are 

interpreted by formation of blue “plus” or 

“minus” sign on each test. Afterwards, nitrazine 

paper is contacted to the vagina for 5 seconds, and 

the color of the paper is compared with a 

colorimetric scale on an enclosed card, and the pH 

value is determined. 

Vaginal MV assessment: Cytological evaluation 

was performed by vaginal smears collected from 

the mid-third of the vaginal lateral wall and 

evaluated in our Pathology Department . In a total 

of 100 exfoliation cells, parabasal cells (P), 

intermediary cells (I), and superficial cells (S) 

were counted and results were expressed as the 

maturation value (MV) of Meisels 3 . Superficial 

cells were assigned a point value of 1.0, 

intermediate cells were assigned a point value of 

0.5, and parabasal cells were assigned a point 

value of 0. The number of cells in each category 

was multiplied by the point value, and the 3 

results were added to arrive at a maturation value. 

A value of 0 to 49 indicated low estrogen effect, a 

value of 50 to 64 indicated moderate estrogen 

effect, and a value of 65 to 100 indicated high 

estrogen effect. All examinations were interpreted 

by the same cytopathologist without prior 

knowledge of the subjects’ data. 

Statistical analysis: In women with negative 

amine test, chi-square test, Pearson correlation test 

and logistic regression test were used where 

appropiate to assess vaginal pH levels and vaginal 

MV with menopausal status and urogenital 

atrophic symptoms. For statistical analysis SPSS 

11.5 (SPSS, Inc, Chicago, IL, U.S.A.) was used. 

RESULTS 

Out of 50 women enrolled, 2 had positive amine 

test and remaining 48 women were included into 

the statistical analysis. The mean age was 54,7 

years (range 47-70 years), mean body mass index 

was 25,5. Of the 48 women 18 (37,5%) had serum 

FSH levels < 40mIU/ml. The mean FSH value, E 2 

value, and MV were 53,3 mIu/ml; 17,4 pg/ml and 

49,1 respectively. The percentage of women with 

pruritus was 18,7% (n=9); dysuri was 27% 

(n=13), vaginal dryness was 64,6% (n=31) and 

dyspareunia was 70,8% (n=34). All of the women 

with urogenital atrophic symptoms had vaginal 

pH values >5.2 (mean value 6,5±0,48), MV< 65 

(mean value 34,7±16,2), serum FSH levels > 40 

mIU/ml and E2 levels < 20 pg/ml. The 

53




demographic and hormonal characteristics of the 

women according to the presence of any of the 

questioned urogenital atrophic symptoms are 

listed in Table 1. 

In women with atrophic symptoms, the age and 

vaginal pH levels were significantly higher than 

women without these symptoms (p




Figure 2: The inverse correlation between serum FSH 

levels and vaginal MV. (r=-0,868; p




use of vaginal pH values, it is possible to monitor 

the introduction dose, change the continuation 

dose and route of therapy in women receiving 

estrogen replacement therapy (ET). In women 

with urogenital atrophic symptoms, who receive 

ERT, elevated vaginal pH decrease to lower levels 

resulting in partially or completely relief of the 

symptoms 9 . In a postmenopausal woman who is 

on ET, vaginal pH value of > 4,5 indicates low 

circulating estradiol levels, which suggests the 

need for an adjustment of dose or route of 

hormone therapy 10 . However in the present study 

decreasing serum E 2 levels were only moderately 

correlated with increasing vaginal pH values and 

decreasing MV. It has been demonstrated 

previously that in some women although serum E 2 

levels are sufficient, vaginal atrophy may persist 

11 . For them, augmenting oral therapy with topical 

vaginal estrogen may be necessary 12 . In the 

present study the demonstrated inverse correlation 

between vaginal pH and MV point out that MV < 

65, similarly, suggests vaginal estrogen deficiency 

although sufficient circulating E 2 levels might be 

detected, and administration of ET or adjustments 

in dose or route of ET would be necessary. 

In women with vaginitis, vaginal pH measurement 

has increased false positive results due to 

overgrowth of facultatively and obligately 

anaerobic bacteria 13, and is useful only for 

monitoring antimicrobial therapy. Therefore, 

amine test is preferably performed simultaneously 

with the vaginal pH measurement to rule out 

vaginal inflammation even in asymptomatic 

women. Conversely, MV is not adversely affected 

and can be safely used to document estrogen 

deficiency in women with vaginal inflammation. 

From previous studies it is known that body mass 

index can influence serum E 2 values and 

consecutively vaginal pH 9 . In the present study 

body mass index of women without vaginal 

atrophic symptoms was similar to women with 

vaginal atrophy. Therefore body mass index was 

not a confounding factor in the present study. 

The positive and negative predictive values should 

be calculated by epidemiologic population-based 

studies. The power of this study is not obviously 

enough to calculate a solid predictive value of 

vaginal pH or MV for menopausal status. On the 

other hand, percentages mentioned reflect the 

population referring to our clinic and might aid 

the clinicians in diagnosis and follow-up. It should 

also be noted that the population included into the 

present study was perimenopausal and early 

postmenopausal women; therefore results 

classified according to urogenital atrophic 

symptoms might not be generalized for older 

women who regard these symptoms as age 

specific. 

In the present study we concluded that vaginal 

MV is similar to vaginal pH in the identification 

of patients who have low estrogen levels or who 

are menopausal. In postmenopausal women 

receiving ET, vaginal MV calculation would aid 

the clinicians, in the same manner as vaginal pH, 

to monitor the therapy, change the dose or route of 

administration, or augment the therapy with a 

topical vaginal estrogen. Methods of deriving 

vaginal MV and pH are simple, practical, quick 

and economic. Moreover, MV can be obtained 

simultaneously with Pap smear test, which is a 

part of routine follow-up, does not require 

additional intervention, and easily interpreted at 

office setting. As a conclusion the present study 

demonstrated that vaginal maturation value 

assessment, unlike serum E 2 levels, is similar to 

vaginal pH values in diagnosis and management 

of estrogen deficiency in perimenopausal and 

early postmenopausal women with urogenital 

atrophic symptoms regardless of receiving past or 

current estrogen replacement therapy. 

REFERENCES 

1. Cruickshank, R., Sharman A. The biology of the 

vagina in human subjects: I, glycogen in the 

vaginal epithelium and its relation to ovarian 

activity; II, the bacterial flora and secretion of the 

vagina at various age-periods and their relation to 

glycogen in the vaginal epithelium; III, vaginal 

discharge of non-infective origin. J Obstet 

Gynaecol Br Empire, 1934(41): 190-207, 208-26, 

369-84. 

2. Rein, M.F., Muller, M. Trichomonas vaginalis and 

trichomonias, in Sexually transmitted diseases, 

K.K. Holmes, et al., Editors. 1990, McGraw-Hill: 

New York. 481-92. 

3. Meisels, A. The maturation value. Acta Cytol, 

1967. 11(4): 249. 

4. Chiechi, L.M., Putignano, G., Guerra, V., 

Schiavelli, M.P., Cisternino, A.M., Carriero, C. The 

effect of a soy rich diet on the vaginal epithelium in 

postmenopause: a randomized double blind trial. 

Maturitas, 2003. 45(4): 241-6. 

5. Zapantis, G., Santoro, N. The menopausal 

transition: characteristics and management. Best 

Pract Res Clin Endocrinol Metab, 2003. 17(1): 33- 

52. 

6. Bachmann, G.A., Nevadunsky N.S. Diagnosis and 

treatment of atrophic vaginitis. Am Fam Physician, 

2000. 61(10): 3090-6. 

7. Capewell, A.E., McIntyre M.A, Elton R.A. Postmenopausal 

atrophy in elderly women: is a vaginal 

smear necessary for diagnosis? Age Ageing, 1992. 

21(2): 117-20. 

8. Davila, G.W., Singh, A., Karapanagiotou, I., 

Woodhouse, S., Huber, K., Zimberg, S., et al. Are 

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women with urogenital atrophy symptomatic? Am 

J Obstet Gynecol, 2003. 188(2): 382-8. 

9. Roy, S., Caillouette, J.C., Roy, T., Faden, J.S. 

Vaginal pH is similar to follicle-stimulating 

hormone for menopause diagnosis. Am J Obstet 

Gynecol, 2004. 190(5): 1272-7. 

10. Caillouette, J.C., Sharp, C.F. Jr., Zimmerman, G.J., 

Roy, S. Vaginal pH as a marker for bacterial 

pathogens and menopausal status. Am J Obstet 

Gynecol, 1997. 176(6): 1270-5; discussion 1275-7. 

11. Benjamin, F., Deutsch, S. Immunoreactive plasma 

estrogens and vaginal hormone cytology in 

postmenopausal women. Int J Gynaecol Obstet, 

1980. 17(6): 546-50. 

12. Notelovitz, M. Estrogen therapy in the management 

of problems associated with urogenital ageing: a 

simple diagnostic test and the effect of the route of 

hormone administration. Maturitas, 1995. 22 Suppl: 

S31-3. 

13. Cauci, S., Driussi, S., De Santo, D., Penacchioni, 

P., Iannicelli, T., Lanzafarne, P. et al. Prevalence of 

bacterial vaginosis and vaginal flora changes in 

peri- and postmenopausal women. J Clin 

Microbiol, 2002. 40(6): 2147-52. 

57


AKUT MYOKARD ENFARKTÜSÜNDE YÜKSELMİŞ SERUM CRP DÜZEYİ VE 

DİABETES MELLİTUS İLE İLİŞKİSİ 

Kenan Topal 1 , Sunay Sandıkçı 1 , Hakan Demirhindi 2 , Ersin Akpınar 3 , Esra Saatçı 3 

1 Adana Numune Eğitim ve Araştırma Hastanesi , Aile Hekimliği, Adana, Türkiye 2 Çukurova Üniversitesi Tıp 

Fakültesi , Halk Sağlığı Anabilim Dalı, Adana, Türkiye 3 Çukurova Üniversitesi Tıp Fakültesi, Aile Hekimliği 

Anabilim Dalı, Adana, Türkiye 

ÖZET 

Amaç: Günümüzde aterosklerozun enflamatuar bir hastalık olduğu ve serum CRP düzeyinin, aterosklerozun 

şiddeti ve genişliği ile korele şekilde yükseldiği kabul edilmektedir. Bu çalışmada, Ocak 2000 ile Temmuz 

2000 tarihleri arasında, Adana Numune Eğitim ve Araştırma Hastanesi Koroner Yoğun Bakım Ünitesi’ne 

(KYBÜ) AMİ tanısıyla yatırılıp trombolitik tedavi uygulanan 55 hastada infarkt tipi ve genişliği ile serum 

CRP düzeyleri arasındaki ilişki incelendi. 

Gereç ve Yöntem: Göğüs ağrısının başlangıcından itibaren 12. saatte serum CRP, kardiak troponin İ, CK- 

MB, LDH, AST, beyaz küre, sedimantasyon düzeyleri incelendi. 

Bulgular: Serum CRP düzeyi ortalama 24.5 mg/L, beyaz küre sayısı ortalama 14.2 X10 3 /ml olup belirgin 

olarak yüksekti. Serum CRP düzeyi ile infarkt tipi ve genişliği arasında ilişki yoktu. Ayrıca CRP yüksekliği 

ile diabetes mellitus varlığı arasında pozitif yönde bir ilişki olduğu görüldü (r: 0.479, p


Kenan Topal ve ark. 

Akut myokard enfarktüsünde yükselmiş serum CRP düzeyi ve diabetes mellitus ile ilişkisi 

GİRİŞ 

Son yıllarda aterosklerozun etiyopatogenezine 

yönelik çalışmalar aterosklerozun enflamatuar bir 

hastalık olduğunu, her evresinde enflamasyonun 

rol aldığını, enflamasyonun aterom plağı 

gelişimini hızlandırdığını ve akut olayların 

oluşumunu çabuklaştırdığını göstermektedir 1-5 . 

Koroner arter hastalıklarında ‘akut faz reaktanları’ 

olan C-reaktif protein (CRP), serum amiloid-A 

(SAA) ve fibrinojen düzeylerinin yükseldiği 

gösterilmiştir. Miyokard nekrozunun olmadığı 

kardiyovasküler hastalıklarda, serum CRP düzeyi 

aterosklerozun şiddeti ve genişliğiyle korelasyon 

göstermektedir 6-9 .Diğer yandan akut myokard 

infarktüsünde (AMİ), dolaşımdaki CRP 

düzeylerinin infarktın genişliği ile korele olduğu 

saptanmıştır 10,11 . Tamamen sağlıklı görünen 

bireylerde ise hs-CRP yüksekliğinin 

kardiyovasküler olaylar açısından, gelecekteki 

artmış riski belirleyen ölçütlerden biri olduğu 

gösterilmiştir 12-14 . Hatta CRP’nin LDL 

kolesterolden daha kuvvetli bir kardiyovasküler 

risk faktörü olduğu ileri sürülmektedir 15 . 

Daha önce yapılan çalışmalarda, AMİ’nde beyaz 

küre sayısının yüksekliğinin epikardiyal kan 

akımında azalma, myokardial perfüzyon 

bozukluğu, dirençli trombüsler ve kötü klinik 

sonuçlarla birlikte olduğu gösterilmiştir 16 . 

Bu çalışmada, AMİ’lü hastalarda infarkt tipi ile 

serum CRP düzeyi ve beyaz küre sayısı arasındaki 

ilişkiyi araştırdık. Koroner Yoğun Bakım 

Ünitesi’ne (KYBÜ), AMİ tanısıyla yatırılıp 

trombolitik tedavi uygulanan hastalarda göğüs 

ağrısının başlangıcından 12 saat sonra serum CRP 

ve CK-MB, kardiak troponin İ düzeyleri ile beyaz 

küre sayısını tayin ettik 17,18 . 

MATERYAL VE METOT 

Bu çalışma, Adana Numune Eğitim ve Araştırma 

Hastanesi KYBÜ’ne 01.01.2000-01.07.2000 

tarihleri arasında AMİ tanısıyla yatırılan 55 hasta 

ile yürütüldü. Hastaların hepsi şiddetli göğüs 

ağrısı ile Acil Servis’e başvurmuşlardı. Yapılan 

muayene ve tetkikler sonucunda AMİ tanısı 

kesinleşen ve ağrı başladıktan sonraki ilk 6 saat 

içinde hastaneye başvuran hastalar çalışma 

kapsamına alındı. Hastaların başvuru sırasındaki 

EKG bulgularına göre AMİ tiplendirilmesi 

aşağıdaki şekilde yapıldı: 

- Akut Anterior Duvar Mİ: D I -AV L , V 3 -V 4 ’de ST 

yükselmesi varsa 

- Akut Anteroseptal Mİ: D I -AV L , V 1 -V 3 ’de ST 


- Akut Yaygın Anterior Mİ: D I -AV L , V 1 -V 6 ’da ST 


- Akut İnferior Mİ: D II -D III -AV F ’de ST 

yükselmesi, V 5 -V 6 ’da ise ST çökmesi varsa 

Tüm hastalara trombolitik tedavi (Streptokinaz 1.5 

MÜ, 45 dakikada intravenöz infüzyon şeklinde) 

uygulandı. Göğüs ağrısının başlangıcından 12 saat 

sonra, alınan kan örneğinde CK-MB, kardiak 

troponin İ, AST, ALT, LDH, beyaz küre, 

sedimentasyon ve CRP düzeylerine bakıldı. 

Kardiyak troponin İ için alınan kan 3000 rpm’de 3 

dakika döndürülerek plazması ayrıldı ve 

Çukurova Üniversitesi Tıp Fakültesi Balcalı 

Hastanesi Merkez Laboratuarı’na gönderildi. 

Ölçümler Microparticle Enzyme Immun Assay 

yöntemiyle (MEIA), Abbott (Troponin I List no. 

3C29) kiti kullanılarak yapıldı ve AMİ için 

diagnostik kesme değeri >2.0 ng/mL idi. 

Diğer tüm hematolojik ve biyokimyasal 

parametreler Adana Numune Eğitim ve Araştırma 

Hastanesi Laboratuarı’nda yapıldı. Serum CRP 

düzeyi, immunotürbidimetrik yöntemle tayin 

edildi ve ölçüm için Cobas Integra otoanalizörü 

kullanıldı. 

Hastaların hepsi sigara içimi, hipertansiyon, 

diabetes mellitus, hiperlipidemi, koroner kalp 

hastalığı yönünden aile öyküsü gibi kardiyak risk 

faktörleri ve kullandığı ilaçlar yönünden 

sorgulandı. 

İstatistik analizler 

Başlangıçta tüm değişkenlere normal dağılıma 

uygunluk testi yapılarak parametrik test 

kriterlerine uyum değerlendirildi. Buna göre 

verilerimiz iki gruba ayrıldı: Birinci grupta, 

hastaların yaşı, beyaz küre sayısı ve alanin 

aminotransferaz (ALT) değerleri yer alıyordu ve 

parametrik yöntemlerle analizleri yapıldı. Diğer 

grup ise sedimentasyon, aspartat amino transferaz 

(AST), laktik dehidrogenaz (LDH), CK-MB, CRP 

ve kardiyak troponin İ’den oluşuyordu ve nonparametrik 

yöntemler uygulanarak analizleri 

yapıldı. Non-parametrik yöntem olarak K- 

independent samples = Kruskal Wallis varyans 

analizi ve parametrik yöntem olarak tek yönlü 

varyans analizi = One way ANOVA (Bonferrari 

karşılaştırmalı) kullanıldı. Yine veriler arasındaki 

korelasyonlar için non-parametrik verilerde 

Spearman sıra korelasyon ve parametrik verilerde 

Pearson korelasyon yöntemleri kullanıldı. 

Ortalama karşılaştırmalarında non-parametrik 

veriler için Mann-Whitney testi, parametrik 

veriler için Student’s t testi kullanıldı. 

59




BULGULAR 

Demografik veriler 

Çalışmaya alınan olgu sayısı toplam 55 olup 

bunların 44’ü erkek (%80) ve 11’i kadın (%20) 

idi. Olguların yaş ortalaması 55.5±13.3 olup, en 

küçük yaş 29, en büyük yaş ise 80 idi. Kadınların 

yaş ortalaması 64±13.2 iken erkeklerde yaş 

ortalaması 53.3±13.2 idi. 

Hastaların %34.5’i (19 kişi) hiç sigara içmemiş, 

%16.4’ü (9 kişi) geçmişte sigara içmiş ve %49.1’i 

ise halen sigara içiyordu. Hastaların %29.1’inde 

hipertansiyon, %16.4’ünde diabetes mellitus ve 

%14.5’inde dislipidemi öyküsü vardı. Yine 

hastaların %25.5’i kardiyovasküler hastalık 

açısından pozitif aile öyküsüne sahipti (Tablo 1). 

Hematolojik ve Biyokimyasal Analizler 

Ortalama serum AST, LDH, CK-MB ve troponin 

İ, beyaz küre sayıları ve enflamatuar yanıtı 

gösteren CRP düzeyleri normalin üzerinde 

bulundu. Ortalama serum CRP değeri 24.5mg/L, 

ortalama beyaz küre sayısı 14.2 X10 9 /L ve 

ortalama serum kardiak troponin İ düzeyi 

859.8ng/ml idi. Bu verilerin normal dağılıma uyup 

uymadıklarını anlamak için Kolmogorov-Smirnov 

normalite testleri uygulandı. Normal dağılıma 

uyan veriler yaş, beyaz küre iken; uymayan veriler 

sedimentasyon, AST, LDH, CKMB, CRP ve 

troponin İ idi. Normal dağılıma uyan verilerin 

analizleri parametrik yöntemlerle yapılırken, 

uymayan verilerin analizleri non-parametrik 

yöntemlerle yapıldı. Hastaların CRP ve troponin İ 

normal dağılım grafikleri Şekil 1’de verilmiştir. 

Tablo 1: Çalışmaya alınan hastaların koroner risk faktörleri açısından durumları 

Cinsiyet Sigara içme durumu HT DM Dislipidemi Aile Öyküsü 

Erkek Kadın Hiç içmemiş Bırakmış İçiyor yok var yok var yok var yok var 

n 44 11 19 9 27 39 16 46 9 47 8 41 14 

% 80.0 20.0 34.5 16.4 49.1 70.9 29.1 83.6 16.4 85.5 14.5 74.5 25.5 

HT: Hipertansiyon, DM: Diabetes Mellitus. 

Sekil 1: 

60




Hematolojik ve Biyokimyasal Verilerin Diğer 

Faktörlere Göre Dağılımı 

Hastaların hematolojik ve biyokimyasal 

değerlerinin sigara içme durumuna göre dağılımı 

Tablo 2, ve diabetes mellitus olup olmadığına 

göre dağılımı Tablo 3’de verilmiştir. 

Serum CRP düzeyi ortalama 24.5mg/L olup akut 

myokard enfarktüsü için CRP’nin kesme değeri 

olan 20mg/L’nin altında kalan olguların sayısı 34 

(%61.8) ve 20mg/L üstünde olan olguların sayısı 

21 (%38.2) idi. CRP yüksekliği ile miyokard 

enfarktüsü tipi arasında anlamlı bir ilişki 

bulunamadı (p>0.05). Halen sigara içen hastalarla 

CRP yüksekliği arasında ters yönde, orta düzeyde 

güçlü bir korelasyon vardı. Diabetes mellitus 

varlığı ile CRP yüksekliği arasında anlamlı, orta 

düzeyde güçlü, pozitif bir ilişki olduğu görüldü 

(p0.05). Halen sigara içen hastalarda 

CRP yüksekliği ile ters yönde bir ilişki bulundu 

(r:-0.710, p




Tablo 3: Hastaların hematolojik ve biyokimyasal değerlerinin diabetes mellitus olup olmadığına göre dağılımı 

Diabetes 

Beyaz 

ESH 

AST 

LDH 

CKMB 

CRP 

Troponin 

Mellitus 

Küre 

1 

U/L 

U/L 

U/L 

mg/L 

İ 

X10 9 /L 

saat 

ng/mL 

yok Ort. 14.7 7.3 257.6 1440.3 254.2 19.4* 870.3 

SD 4.4 7.1 175.7 841.6 207.6 20.0 719.8 

n 46 46 46 46 46 37 46 

var Ort. 11.5 29.3 145.2 1246.6 111.0 55.9* 805.8 

SD 3.2 18.3 138.5 721.7 79.9 29.9 661.6 

N 9 9 9 9 9 6 9 

Tablo 4: CRP değerleri ile diğer risk faktörleri arasındaki ilişki 

CRP Sigara Hipertansiyon Diabet Dislipidemi Aile öykü AMİ tipi 

1.000 -0.710* -0.117 0.479 ** 0.099 0.099 0.105 

*Bir yönlü ve iki yönlü Spearman korelasyon analizine göre p




yüksekliğinin, kalp yetmezliği ile korelasyon 

gösterdiği fakat infarkt alanı ile korelasyon 

göstermediğini bulmuştur 22 . Pietila 1996 yılında 

ise AMİ geçiren 188 hastada yaptığı araştırmada 

AMİ sonrasında ilk 6 ayda ölen hastaların 

enfarktüs sonrası CRP düzeylerinin yüksek 

olduğunu, CRP düzeyleri ile infarkt alanı arasında 

korelasyon olmadığını göstermiştir 11 . 

Çalışmamızda, ortalama serum CRP düzeyi 

24.5mg/L olup normal değerlerin ve kesme değeri 

olan 20mg/L’nin üzerindeydi. Ancak CRP 

yüksekliği ile miyokard enfarktüsü tipi arasında 

anlamlı bir ilişki yoktu. Bu sonuçlar, Pietila’nın 

çalışmalarındaki sonuçlar ile uyumludur. Serum 

CRP düzeyleri olguların 34’ünde (%61.8) 

20mg/L’nin altında, 21’inde (%38.2) ise 

20mg/L’nin üstündeydi. Pietella’nın da bulduğu 

gibi trombolitik tedavi ile sağlanan başarılı 

reperfüzyon sonucu CRP değerlerinin çok fazla 

yükselmediğini düşünüyoruz. 

Diğer yandan çalışmamızdaki CRP değerleri, 

diabeti olanlarda anlamlı olarak (p




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64


SOCIAL ISOLATION STRESS IN THE EARLY LIFE REDUCES THE SEVERITY OF 

COLONIC INFLAMMATION 

Sevgin Özlem İşeri 1 , Fatma Tavsu 1 , Beyhan Sağlam 2 , Feriha Ercan 2 , Nursal Gedik 3 , Berrak C.Yeğen 1 

1 Marmara University, School of Medicine, Physiology, Istanbul, Türkiye 2 Marmara University, School of 

Medicine, Histology and Embryology, Istanbul, Türkiye 3 Kasımpaşa Military Hospital , Biochemistry , 

Istanbul, Türkiye 

ABSTRACT 

Objective: To investigate whether the early-life stress interact with a brief stress exposure and acute colonic 

inflammation in adulthood. 

Methods: Female Sprague–Dawley rats on the postnatal 21st day were exposed to isolation stress until they 

reach 250 g. On the last 3 days with or without isolation, water-avoidance-stress (WAS) for 30 min/day or 

acetic acid(5 %) colitis were performed. After the last WAS or on the 4th day of colitis, rats were decapitated 

to collect serum for TNF-alpha levels, colonic tissues for histological analysis, myeloperoxidase activity 

(MPO), evidence of neutrophil infiltration, and glutathione (GSH) levels, a key antioxidant. 

Results: In the non-isolated and isolated groups, WAS and colitis both elevated the TNF-alpha, MDA levels 

and MPO activity compared to control (p


Sevgin Özlem İşeri, et al. 

Social isolation stress in the early lifee reduces the severity of colonic inflammation 

INTRODUCTION 

Stress of various types during daily life, and 

adequate responses to these stressors are 

necessary for survival. If the severity or the 

chronicity of the stressful experience exceeds the 

adaptive capacity, the individual will be 

predisposed to illness and disease in multiple 

organ systems 1 . Stress can induce inflammatory 

responses in various organs and when stress is 

chronic it may induce or aggravate chronic 

inflammatory diseases. Although the influence of 

psychological stress on the symptoms and clinical 

course of intestinal inflammatory processes has 

long been recognized, it has recently received the 

attention of the researchers 2 . Recent data suggest 

that stress induced alterations in gastrointestinal 

inflammation may be mediated through changes 

in hypothalamic-pituitary-adrenal (HPA) axis 

function and alterations in bacterial-mucosal 

interactions, and via mucosal mast cells and 

mediators such as corticotrophin releasing factor 

(CRF) 3 . 

Psychological stress in adulthood has long been 

reported to increase disease activity in 

inflammatory bowel disease (IBD), and recent 

well-designed studies have confirmed that chronic 

stress and depression increase the likelihood of 

relapse in patients with quiescent IBD 3 . Although 

long-term perceived stress in patients with 

ulcerative colitis increases the risk of exacerbation 

over a period of months to years, it was shown 

that short-term stress does not trigger exacerbation 

4 . Similarly, it has been shown that different stress 

models in animals may have varying effects on 

colonic inflammation induced by different 

methods. Partial restraint stress applied during 4 

consecutive days causes exacerbation of 2,4,6- 

trinitrobenzenesulfonic acid (TNB)-induced 

colitis in adult rats 5 . In contrary, we have 

previously shown that acute stress exposure 

applied as water avoidance stress (WAS) 6 or 

electric shock 7 reduces the severity of colitis 

induced by acetic acid or TNBS, respectively. 

A large number of studies have also shown that 

early-life trauma can affect the development and 

clinical course of intestinal disorders and 

reactivate inflammation in experimental colitis 2,5 . 

The neonatal period, roughly extending in rats 

from birth to day 14, is often referred to as a stress 

hyporesponsive period characterized by a 

diminished adrenocorticotropin and corticosterone 

response to most stressors 8 . 

Repeated maternal deprivation during this 

neonatal period yields to a more tentative 

behavior and decreased gain of body weight 9, 

exacerbates the severity of trinitrobenzene 

10 

sulfonic acid (TNBS)-induced colitis and 

increases gastric ulcer susceptibility in the adult 

11 . On the other hand, brief maternal separation 

has a protective effect on adult stress exposure, 

protecting the animals from dextran sodium 

sulphate (DSS)- induced colitis, while the nonhandling 

condition sensitizes mucosa to DSS 

exposure 12 . Social isolation stress during the postweaning 

period also leads to behavioural and 

neurochemical sequelae in rats 13 . However, the 

effect of post-weaning social isolation stress on 

secondary stress exposures during the later phases 

of life, whether it will alleviate or exacerbate the 

inflammatory responses, is not clarified yet. 

Based on the current knowledge about the impact 

of stress on the course of inflammatory bowel 

diseases, the present study was designed to 

investigate whether the early-life stress at the 

post-weaning period might interact with a brief 

stress exposure and acute colonic inflammation in 

adulthood. 

METHODS 

Animals 

Adult female Sprague–Dawley rats (250–300 g) 

were kept in a light- and temperature-controlled 

room with 12:12 h- light-dark cycle, where the 

temperature (22 ± 0.5 ºC) and relative humidity 

(65–70 %) were kept constant. The animals were 

fed a standard pellet and food was withdrawn 

overnight before colitis induction. Access to water 

was allowed ad libitum. Experiments were 

approved by the Marmara University School of 

Medicine Animal Care and Use Committee. 

Social isolation stress 

Dams and their litters were assigned to the nonisolation 

(n=18) protocol or to social isolation 

stress (n=18) protocol. To induce post-weaning 

social isolation stress, rats were removed from 

their cages and dams on the postnatal 21 st day and 

were placed in individual plastic cages to be kept 

in another room. Before the experiments, pups 

were allowed to reach at least to 250 g body 

weight for 60 days. The growth of the animals 

was followed only by inspection and the rats were 

not handled following the separation. The animals 

were transferred to clean cages with new chip 

bedding at weekly intervals without handling. 

66




Water avoidance stress (WAS) 

At the end of the 60-days protocol with or without 

isolation, when the required weight was reached, 

water avoidance stress (WAS) was performed as 

previously described 14 . Rats were individually 

placed onto a plastic platform (6 cm × 6 cm × 8 

cm) located in the middle of a plastic cylinder 

container (50 cm × 56 cm) filled with warm water 

(25 ºC) up to 1 cm below the height of the 

platform. Stress sessions, which lasted for 30 min, 

were performed for 3 consecutive days between 

16:00 and 16:30 p.m. to minimize any diurnal 

variation in the responses. Rats were then put 

back to their home cages with free access to water 

and food. 

Induction of colitis 

Ath end of 60–days follow-up period, another 

group of rats (n=12; isolated and non-isolated) 

were fasted for 18 h before the induction of 

colitis. Colitis was induced by a modification of 

the method introduced by MacPherson and 

Pfeiffer 

15 . Under light ether anesthesia, a 

polyethylene catheter (PE-60) was inserted into 

the colon with its tip positioned 8 cm from the 

anus. To induce colitis, a single solution of 1 ml 

of 5 % (v/v) acetic acid diluted in saline (pH 2.3) 

was instilled. 

Experimental protocol 

On the 4th day, immediately after the last WAS 

exposure or on the 4th day of colitis induction, 

rats were decapitated. The rats in the control 

group (n=12) were handled at the same time 

points as in the WAS-applied group, but were not 

placed on the platform and isotonic saline was 

instilled intracolonically instead of acetic acid. 

Control rats were decapitated on the 4 th day of 

intracolonic saline application. Trunk blood was 

collected for the assessment of TNF-α levels. The 

distal 8 cm of the colon were opened down their 

mesenteric borders and cleansed of luminal 

contents. Colonic tissue was obtained from each 

animal and stored at −80 ºC until the 

determination of tissue myeloperoxidase activity 

(MPO), as an indirect evidence of neutrophil 

infiltration, and the level of glutathione (GSH), a 

key antioxidant. For the histological analysis, a 1 

square cm sample at 8 cm from anus was obtained 

from each animal to be fixed in formaldehyde. 

Measurement of serum TNF-α level 

Serum TNF-α level was evaluated by a RIA– 

IRMA (radioimmunoassay–immunoradiometric 

assay) method. All samples were assayed in 

duplicates using the commercial kit (Biosource 

Europe S.A., Nivelles, Belgium). The activity of 

radioactive assays was measured by a gamma 

counter (LKB WALLAC 1270 RACK, Canada) 

and the values were expressed as ng/ml. 

Myeloperoxidase (MPO) activity 

Tissue-associated myeloperoxidase (MPO) 

activity was determined in the colonic samples as 

an indication of accumulation of neutrophils. All 

reagents for MPO assay were obtained from 

Sigma. The tissue samples (0.2–0.3 g) were 

homogenized in 10 volumes of ice-cold potassium 

phosphate buffer (50 mM K 2 HPO 4 , pH 6.0) 

containing hexadecyltrimethylammonium 

bromide (HETAB; 0.5%, w/v). The homogenate 

was centrifuged at 12,000 rpm for 10 min at 4 ºC, 

and the supernatant was discarded. The pellet was 

then rehomogenized with an equivalent volume of 

50 mM K 2 HPO 4 containing 0.5% (w/v) 

hexadecyltrimethylammonium bromide and 10 

mM ethylenediaminetetraacetic acid (EDTA, 

Sigma). MPO activity was assessed by measuring 

the H 2 O 2 -dependent oxidation of o- 

dianizidine·2HCl. One unit (U) of enzyme activity 

was defined as the amount of the MPO present per 

gram of tissue weight that caused a change in 

absorbance of 1.0 min −1 at 460 nm and 37 ºC 16 . 

Determination of glutathione level 

Tissue samples were homogenized in 10 ml vol. 

of ice-cold 10% trichloroacetic acid, in an Ultra 

Turrax tissue homogenizer. Homogenized tissue 

samples were centrifuged at 3000 rpm for 15 min 

at 4 ºC. The supernatant was removed and 

recentrifuged at 15,000 rpm for 8 min. 

Glutathione measurements were performed using 

a modification of the Ellman procedure 17 . 

Histological assessment of colonic injury 

For light microscopic investigations samples from 

the colon were fixed with 10% formaldehyde, 

dehydrated in graded alcohol series, cleared with 

toluen and embeded in paraffin. Tissue sections (5 

µm) were stained with hematoxylin and eosin 

(H&E) for general morphology and examined 

under a Olympus BX51 photomicroscope (Tokyo, 

Japan). All tissue sections were examined 

microscopically for characterization of 

histopathological changes by an experienced 

histologist (F.E.) who was unaware of the 

treatment conditions. Assessment of the colonic 

injury was performed using the previously 

described criteria: Damage/necrosis (0: None, 1: 

Localised, 2: Moderate, 3: Severe); Submucosal 

edema (0:None, 1: Mild, 2: Moderate, 3: Severe); 

67




Inflammatory cell infiltration (0: None, 1: Mild, 2: 

Moderate, 3: Severe); Vasculitis (0: None, 1: 

Mild, 2: Moderate, 3: Severe); Perforation (0: 

Absent, 1: Present); with a maximum score of 13 39 

Statistics 

The results are expressed as means ± SEM. 

Following the assurance of normal distribution of 

data, one-way analysis of variance (ANOVA) was 

used for multiple comparisons and Student's t-test 

was used to evaluate the level of statistical 

significance between pairs (GraphPad Software, 

San Diego, CA, USA). Differences were 

considered statistically significant if P




Figure 3: Micrographs illustrating the histological 

appearances of colonic tissues in different experimental 

groups. Non-isolated control group (A), regular colon 

morphology; non-isolated WAS group (B), mild 

inflammatory cell infiltration; non-isolated colitis group (C), 

severe damage of mucosa with epithelial degeneration, 

severe submucosal edema, vasculitis and inflammatory cell 

infiltration; isolated control group (D), mild inflammatory 

cell infiltration; isolated WAS group (E) mild inflammatory 

cell infiltration; isolated colitis group (F) mild damage of 

mucosa with localized epithelial degeneration, moderate 

submucosal edema, vasculitis and inflammatory cell 

infiltration. H&E staining, original magnifications, ×100. 

Epithelial degeneration (→), submucosal edema (s) and 

inflammatory cell infiltration (*). 

On the other hand, colonic GSH in the rats with 

colitis that were previously isolated was found to 

be similar to that of the control levels, showing 

that the depletion of colonic GSH by colitis does 

not occur in chronically stressed animals. In 

contrary, the pre-existing isolation stress did not 

alter the reduction in the colonic GSH induced by 

the acute WAS. 

MPO activity, indicating tissue neutrophil 

infiltration, was elevated in the colonic tissues of 

both the isolated and non-isolated rats that were 

exposed to acute WAS (p




early life, but clearly beyond the vulnerable 

period, yields to a reduction in the inflammatory 

response to colitis induction, which may suggest a 

decrease in the HPA activation. As the other mild 

stressors, post-weaning isolation may induce an 

adaptive response to protect the individual to 

subsequent pathological conditions. Thus, adult 

rats exposed to isolation stress during their postweaning 

period are protected from chemically 

induced colitis. 

Experimental and clinical studies have shown that 

any harmful tissue event is perceived by 

macrophages and monocytes, which in turn 

secrete cytokines. Cytokines then activate 

inflammatory cells (neutrophils, 

macrophages/monocytes, platelets, mastocytes) 

releasing large amounts of toxic oxygen and 

nitrogen species, which cause cellular injury via 

several mechanisms. Glutathione is an important 

constituent of intracellular protective mechanisms 

against various noxious stimuli including 

oxidative stress. However, reduced glutathione as 

the main component of endogenous non-protein 

sulfhydryl pool, is known to be a major low 

molecular weight scavenger of free radicals in the 

cytoplasm 31,32 . In accordance with the previous 

reports, our results support the notion that 

depletion of tissue GSH, as observed in the acetic 

acid- and WAS-induced colonic injury, is one of 

the major factors that permit tissue damage. Since 

exposure to isolation stress previously has reduced 

the colonic GSH depletion, it appears that the 

protective effect of the early life stressor may 

involve the maintenance of antioxidant capacity in 

protecting the colonic tissue against oxidative 

stress. However, the presence of isolation stress in 

the early life period has not altered the WASinduced 

GSH depletion. Interestingly, the 

previous stress has not exacerbated the destruction 

of antioxidant capacity induced by an acute 

stressor. 

The tissue-associated MPO, which is known as 

the index of neutrophil infiltration, plays a 

fundamental role in oxidant production by 

neutrophils 33 . In our observation, elevated MPO 

levels in the colonic tissues indicate that 

neutrophil accumulation contributes to the colitisand 

WAS-induced oxidative injury. As shared by 

other inflammatory disorders in the gut, active 

lesions in the ulcerative colitis involve the 

migration of activated neutrophils and 

macrophages 34 . A growing body of evidence 

suggests that neutrophils release chemotactic 

substances, which further promote neutrophil 

migration to the tissue, activate neutrophils, and 

increase the damage 35 . In the present study, 

colitis-induced increase in MPO activity was 

relatively less when the rats were exposed to 

isolation stress previously, suggesting that the 

protective effect of the early stressor on colonic 

inflammation may involve the inhibition of 

neutrophil recruitment, which then inhibits the 

adhesion and aggrevation of neutrophil 

leukocytes 36 . On the other hand, it seems that 

isolation stress during post-weaning period 

protected the colonic tissue against WAS 

exposure by a mechanism independent of 

neutrophil accumulation. However, the TNF-α 

level was already increased in the rats that were 

exposed to isolation stress, suggesting that the 

cytokine response was enhanced by the early life 

stressor. Nevertheless, the important function of 

antibodies in recognizing and neutralizing some of 

the damaging cytokines like TNF-a may be 

changed by alterations in the HPA axis 12 . The 

present data demonstrates that hypersensitivity to 

inflammation, via increased synthesis or release of 

proinflammatory mediators, is not further 

enhanced by new stressors of chemical or 

psychological origin. 

The newborn is totally dependent on maternal 

care. Feeding and maintaining optimal body 

temperature depend on parental sensitivity to the 

offspring's signals, and tactile stimulation appears 

to be crucial for the infant's biological and 

behavioral responses 37 . Therefore, repeated 

maternal separation delays the gain in body 

weight 28 . Since neonatal stress consisted of early 

weaning, milk deprivation has been proposed as a 

major factor involved in numerous long-term 

disorders, such as increased ulcer 

susceptibility 11,38 . However, in our study, the rats 

were isolated after the weaning period and the 

weight gain was found to be similar in both the 

isolated and non-isolated rats. Since the separated 

animals were capable of self-care, isolation did 

not directly affect the feeding behavior. Along 

with the behavioral symptoms, the current data 

show that post-weaning isolation has a protective 

effect on chemically induced colonic 

inflammation. Furthermore, isolation following 

weaning does not exacerbate colonic response to 

subsequent acute stressors. In conclusion, our 

results show that stress exposure does not always 

contribute to the exacerbation of the inflammatory 

bowel disease. Stress, depending on intensity, 

duration and the time of exposure, may elicit 

adaptive or maladaptive physiological changes, 

providing advantageous or deleterious effects on 

psychosomatic vulnerability. 

70




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72

CASE REPORTS 

LAPAROSCOPIC APPROACH FOR EPIPHRENIC ESOPHAGEAL DIVERTICULA 

Osman Kurukahvecioğlu, Ekmel Tezel, Bahadır Ege, Hande Köksal, Emin Ersoy 

Gazi Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ankara, Türkiye 

ABSTRACT 

Epiphrenic diverticula of the esophagus are rare disorders frequently associated with esophageal dismotility 

that is thought to be the cause of the diverticulum and some of the symptoms. Treatment is surgery and only 

indicated to the symptomatic patients. The operation can be performed successfully by laparoscopy, which 

offers good access to the distal esophagus and the inferior mediastinum. A 68 year-old woman presented 

with symptoms of heartburn, regurgitation and vomiting. Two diverticula located in distal esophagus were 

detected with barium esophagography and endoscopy. The biggest diverticulum was resected by the 

endoscopy assisted laparoscopic approach. 

Laparoscopic approach to epiphrenic diverticula seems to be feasible and safe provided when surgeons 

trained in minimally invasive procedures of the gastroesophageal junction perform it. 

Keywords: Esophageal diverticula, minimal invasive surgery, laparoscopy 

ÖZET 

EPİFRENİK ÖZAFAGUS DİVERTİKÜLLERİNE LAPAROSKOPİK YAKLAŞIM 

Epifrenik özafagus divertikülleri nadir rastlanan bir hastalık olup sıklıkla divertiküllerin ve semptomların 

nedeni olduğu düşünülen özafagus motor bozukluklarıyla birliktelik gösterir. Tedavisi cerrahi olup sadece 

semptomatik hastalara uygulanmaktadır. Ameliyat alt özafagus ve mediastende iyi görüş sağlayan 

laparoskopik yöntemle başarılı bir şekilde yapılabilir. Yazımızda göğüste yanma ve kusma şikayeti ile 

başvuran 68 yaşındaki bir kadın hasta sunulmaktadır. Baryumlu özafagografi ve endoskopisinde alt 

özafagusta yerleşmiş iki adet divertikül saptanan hasta intraoperatif endoskopi yardımıyla laparoskopik 

olarak ameliyat edildi. Epifrenik divertiküllere laparoskopik yaklaşım,gastroözafageal bölge konusunda 

deneyimli cerrahlar tarafından güvenle uygulanabilmektedir. 

Anahtar Kelimeler: Özafagus divertikülleri, minimal invaziv cerrahi, laparoskopi 

INTRODUCTION 

Esophageal diverticula are rare diseases mostly 

classified by location and etiology. The exact 

prevalence of this condition is not known because 

asymptomatic cases are usually not discovered. 

Symptoms are variable. Some patients have only 

mild dysphagia however other patients have 

worsening and incapacitating symptoms like 

severe dysphagia, regurgitation with recurrent 

episodes of pneumonia due to aspiration, 

heartburn, cardiac arrhythmias, obstruction, 

weight loss, chronic cough and halitosis 1 . 

Diagnosis is radiological. All patients with 

suspicion of having epiphrenic diverticulum 

should undergo barium study in order to 

document the location of the diverticulum, 

maximal diameter of the pouch, diameter of the 

diverticular neck, the appearance of the 

gastroesophageal junction and the presence of 

tertiary contractions. By the help of the endoscopy 

findings of esophagitis or those suggestive of a 

motility disorder can be recorded also 1 . 

The treatment of these diverticula is surgical. The 

decision must be made with regarding the 

patient’s symptoms, operative risk and 

complication and the surgical expertise locally 

available, considering the rarity of the disease. 

With the introduction of minimally invasive 

surgical techniques esophageal diseases have been 

successfully treated by laparoscopic approach. 

Laparoscopy offers good access to the distal 

esophagus and the inferior mediastinum therefore 

it should be considered as an alternative to the 


Hande Köksal 

e-mail: drhandeniz@yahoo.com 

Gazi Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ankara, Türkiye 

73 

Marmara Medical Journal 2006;19(2);73-76


Osman Kurukahvecioğlu, et al 

Laparoscopic approach for epiphrenic esophageal diverticula 

traditional transthoracic approach and may 

eventually become the standard technique 1,2 . 

Here we report a case of lower esophageal 

diverticulum treated successfully with 

laparoscopic approach. 

CASE PRESENTATION 

A 68 year-old woman presented at our clinic with 

symptoms of heartburn, regurgitation and 

vomiting. The duration of symptoms was six 

months. The diagnostic work-up consisted of 

barium esophagography and endoscopy. She did 

not have any signs during the endoscopy 

suspecting a gastro-esophageal reflux so we did 

not perform pH monitoring. Barium study showed 

two diverticula located in the distal third of the 

esophagus. The average sizes of the pouches were 

4 cm and 2 cm (figure 1). The diverticula were 

located 6-7 cm above the cardia measured by 

endoscopy and a hiatal hernia was also diagnosed. 

No findings suggestive of primary esophageal 

motility disorder like dilatation of the esophagus, 

retained food, and resistance at the level of 

gastroesophageal junction or tertiary contractions 

were recorded during endoscopy so the symptoms 

of the patient were thought to be related with the 

compression of the larger diverticulum to the 

distal esophagus. Following a complete 

preoperative evaluation, the patient was scheduled 

for laparoscopic operation. The position of the 

patient, surgeon and the trocar sites were the same 

as for the laparoscopic treatment of functional 

diseases of the esophagogastric junction. 

The patient was placed on the operating table in 

the lithotomy position with a 30º reverse 

Trendelenburg. The surgeon was standing 

between the legs. Pneumoperitoneum was 

established and five operating ports were placed 

as usual from the abdomen. A 30º-angled scope 

was used. After dividing phreno-esophageal 

membrane, the diaphragmatic crura were exposed. 

The esophagus was isolated and completely 

encircled with a rubber tape for traction. Blunt 

dissection was carried out in the mediastinum 

until 8-10 cm above the diaphragmatic crura 

staying close to the esophageal surface. At the 

same time the larger diverticular pouch was 

identified by endoscopy and isolated up to the 

superior margin of its neck and then resected with 

a linear endoscopic stapler with the nasogastric 

tube inside the esophageal lumen. Intraoperative 

endoscopy was used in order to avoid the 

narrowing of the lumen by the stapler and to 

detect an incomplete resection, also to check the 

stapled suture line for any leak. Endoscopically 

there was no evidence of leak at the suture line 

therefore suture of the esophageal musculature 

was not performed (figure 2). The smaller 

diverticulum was not resected because of being 

asymptomatic. A Toupet fundoplication was 

chosen for the repair of the hiatal hernia. The 

procedure was finished after 95 minutes. The 

postoperative course was uneventful. She had 

check-up swallow radiography with water-soluble 

contrast medium on the 6th postoperative day and 

no leakage was shown. She resumed oral intake 

on the same day and discharged on day 8. She has 

been totally asymptomatic during a 10 months 

follow-up period. 

Figure 1: Barium study images showed the diverticula 

located in the distal third of the esophagus. 

Figure 2: Endoscopically there was no evidence of leak at 

the suture line 

74


Osman Kurukahvecioğlu, et al. 

Laparoscopıc approach for epiphrenic esophageal diverticula 

DISCUSSION 

Esophageal diverticula are rare. The true 

incidence is unknown. The etiology, symptoms 

and therapeutic requirements suggest a 

categorization in three forms: pharyngoesophageal 

(Zenker diverticula), parabronchial 

and epiphrenic diverticula. 

Epiphrenic diverticula arise within the distal 10 

cm of the thoracic esophagus. The exact 

prevalence of this condition is not known because 

asymptomatic cases are usually not discovered. It 

seems to occur less frequently than Zenker’s 

diverticula with a ratio of 1:5 2 . Most of these are 

found in middle aged- elderly patients and male 

gender has a slight predominance. 

Pathophysiology of the epiphrenic diverticulum is 

still unclear. The herniation of the mucosa and 

submucosa through a defect in the muscular layer 

is probably caused by a longstanding impairment 

of the esophageal motor activity. However the 

associated motor disorder is not always 

recognized and diagnosed. 

Symptoms are variable. Many patients do not 

have any symptoms and some have only mild 

dysphagia. In these patients diverticulum is an 

incidental finding on barium swallow done for 

unrelated reasons. However other patients have 

worsening and incapacitating symptoms like 

severe dysphagia, regurgitation with recurrent 

aspiration and pneumonia, heartburn, cardiac 

arrhythmias, obstruction, weight loss, chronic 

cough and halitosis 1 . Bleeding, spontaneous 

perforation and also carcinoma have been noted 3 . 

Diagnosis is radiological. All patients with 

suspected epiphrenic diverticulum should undergo 

barium study. Exact identification of the 

diverticulum is of crucial importance for a 

successful procedure. Therefore endoscopysupported 

visualization of the diverticulum has 

been recommended 4 . Manometry is mandatory to 

define associated motility disorders. If gastroesophageal 

reflux is suspected, a 24-hour pH 

study can also be performed. 

The treatment of these diverticula is surgical. 

However, the presence of a diverticulum is not an 

indication for surgery. There is almost a 

consensus that surgery should be preserved for 

symptomatic patients 5 . The desicion must be 

balanced between the patient’s symptoms, the 

complication and operative risk. Patients with 

minimal symptoms should be managed 

conservatively 5,6 . If symptoms are incapacitating 

an operation should be advised. Neither size nor 

location of the diverticulum is correlated with 

symptoms 2 . The traditional surgical treatment for 

an epiphrenic diverticulum consists of an 

esophageal myotomy, diverticulectomy or 

diverticulopexy and an anti-reflux procedure 

usually through a thoracotomy. Using 

conventional techniques diverticula in the lower 

portion of the esophagus can be operated with 

morbidity and mortality rates of 33% and 9% 

respectively 2 . With the introduction of minimally 

invasive surgical techniques, esophageal diseases 

have been successfully treated by laparoscopic 

approach. Because thoracoscopic surgery can 

have some troubles especially in dissection and 

placing the stapler, laparoscopic route is chosen to 

minimize the risk of incomplete resection and 

narrowing of the passage by the stapled suture 

line. Simultaneous endoluminal visualization can 

be used in order to accelerate the procedure, to 

allow proper placement of the stapler and finally 

giving opportunity to check the suture line for any 

leak. All pathophysiologic problems of this 

disorder can be solved by laparoscopy: the 

removal of the diverticulum, the treatment of the 

motor disorder and the reflux. But the procedure 

is still a matter of discussion while it has been 

stated that diverticulectomy alone is enough if no 

motor abnormality is detected 7,8 . If there is motor 

disturbance in esophagus then myotomy should be 

added 9 . Also the relationship between the motility 

abnormality and the development of the 

diverticulum is described to be more likely around 

60% by Streitz et all 7 . In our patient no motor 

abnormality was recognized so myotomy was not 

performed. We do recommend the use of a partial 

wrap of fundus if the patient has reflux on 

preoperative workup, because total fundoplication 

can create an obstacle for the esophageal flow and 

this may result in leakage from the suture line or 

recurrence of a diverticulum. 

In conclusion, laparoscopic approach to 

epiphrenic diverticula seems to be feasible and 

safe provided when surgeons trained in minimally 

invasive procedures of the gastroesophageal 

junction perform it. 

REFERENCES 

1. Costantini M, Zaninotto G, Rizzetto C, Narne S, 

Ancona E. Oesophageal diverticula. Best Pract Res 

Clin gastroenterol 2004; 18: 3-17. 

2. Benacci JC, Deschamps C, Trastek VF, Allen MS, 

Daly RC, Pairolero PC. Epiphrenic diverticulum: 

Results of surgical treatment. Ann Thorac Surg 

1993; 55: 1109-1113. 

75


Osman Kurukahvecioğlu, et al. 

Laparoscopıc approach for epiphrenic esophageal diverticula 

3. Schultz SC, Byrne DM, De Cunzo P, Byrne WB. 

Carcinoma arising within epiphrenic diverticula. A 

report of two cases and review of the literature. J 

Cardiovasc Surg 1996; 37: 649-651. 

4. Rosati R, Fumagalli U, Bona S, Bonavina L, 

Peracchia A. Diverticulectomy, myotomy and 

fundoplication through a laparoscopy: A new 

option to treat epiphrenic esophageal diverticula? 

Ann Surg 1998; 227: 174-178. 

5. Evander A, Little AG, Ferguson MK, Skinner DB. 

Diverticula of the mid and lower esophagus: 

Pathogenesis and surgical management. World J 

Surg 1986; 10: 820-828. 

6. Fernando HC, Luketich JD, Samphire J, et al. 

Minimally invasive operation for esophageal 

diverticula. Ann Thorac Surg. 2005; 80: 2076- 

2080. 

7. Streitz JM, Glick ME, Ellis H. Selective use of 

myotomy for treatment of epiphrenic diverticula: 

Manometric and clinical analysis. Arch Surg 1992; 

127: 585-588. 

8. Gockel I, Eckardt VF, Junginger T. Epiphrenic 

diverticulum: Possible causes and surgical therapy. 

Chirurg 2005; 76: 777-782. 

9. Abe T, Tangoku A, Oka M. Esophageal diverticula. 

Nippon Geka Gakkai Zasshi. 2003; 104: 601-605. 

76

CASE REPORTS 

NEONATAL MIXED SEX-CORD STROMAL TUMOR OF THE TESTIS: A CASE 

REPORT 

Asıf Yıldırım 1 , Erem Başok 1 , Adnan Başaran 1 , Ebru Zemheri 2 , Reşit Tokuç 1 

1 SB İstanbul Göztepe Eğitim ve Araştırma Hastanesi, Üroloji, İstanbul, Türkiye 2 SB İstanbul Göztepe Eğitim 

ve Araştırma Hastanesi, Patoloji, İstanbul, Türkiye 

ABSTRACT 

Sex cord-stromal tumors of the testis are rare. We report a mixed type sex-cord stromal tumor in neonate. 

According to published reports, sex-cord stromal testis tumors exhibit benign behavior in prepubertal 

patients. However, undifferentiated stromal tumor with a large number of mitotic figures may exhibit 

metastatic behavior. 

Keywords: testis, sex cord-stromal tumor, neonate 

NEONATAL TESTİS MİKST SEKS-KORD STROMAL TÜMÖR: OLGU SUNUMU 

ÖZET 

Testisin seks-kord stromal tümörü nadir olarak görülmektedir. Bu yazıda, neonatal testisin mikst tipte sekskord 

stromal tümör olgusu sunuldu. Literatüre bakıldığında, prepübertal dönemde testisin seks-kord stromal 

tümörleri benign seyir göstermektedir. Buna karşın, çok sayıda mitotik aktivite ile diferansiye-olmayan 

stromal tümör malign davranış gösterebilir. 

Anahtar Kelimeler: testis, seks kord-stromal tümör, neonatal 

INTRODUCTION 

Testis tumors in the neonate are extremely rare 

and with the exception of the previous reports of 

the Tumor Registry data, few cases have been 

documented in the literature. 1 Sex-cord stromal 

testis tumors represent only 5% of all testicular 

neoplasms, and include Leydig cell, Sertoli cell, 

juvenile granulosa cell, thecal cell tumors, mixed 

cell types and undifferentiated tumors. 2 We report 

a case of neonatal mixed sex-cord stromal tumor 

and discuss its diagnosis and treatment. To our 

knowledge no such cases have been reported in 

the literature. 


An otherwise healthy full-term male infant was 

referred for a markedly enlarged and firm right 

testis. On physical examination both testes were 

descended, and the right testis was enlarged and 

non-tender (Figure 1). Color Doppler ultrasound 

showed a solid cystic mass with 

microcalcification, which had entirely replaced 

the normal testicular parenchyma (Figure 2). 

Serum AFP was 13.927 ng/ml (normal range 0.6- 

16.387). Inguinal exploration and right radical 

orchiectomy were performed. The gross 

appearance was primarily of tan-yellow nodular 

lesions containing multiple thin-walled cysts with 

hemorrhagic fluid (Figure 3). Pathological 

examination revealed small nests, narrow cords 

and thick trabeculae, tubular structure enveloped 

by fine connective tissue and a mixed sex-cord 

stromal (sertoli cell and juvenile granulosa cell) 

tumor that had completely replaced the testis. 

(Figure 4). Immunohistochemical study of the 

tumor showed a strong positivity for vimentin, 

inhibin-alfa and a negative staining for alphafetoprotein 

(AFP), Carcinoembryogenic antigen 

(CEA), placental-like alkaline phosphatase 

(PLAP), cytokeratin, epithelial membrane antigen 

(EMA) and desmin (Figure 5). The patient did 

well postoperatively and at 16 months follow-up 

AFP was normal. 


Asıf Yıldırım 

e-mail: asifkad@superonline.com 

SB İstanbul Göztepe Eğitim ve Araştırma Hastanesi, Üroloji, İstanbul, Türkiye 

77 



Asıf Yıldırım, et al 

Neonatal mixed sex-cord stromal tumor of the testis: a case report 

Figure 1: Enlarged right testis 

Figure 3: Gross appearance of testis 

Figure 2: Color Doppler Ultrasonography of the right testis 

Figure 4: Small nests (arrow) enveloped by fine connective 

tissue (H&E, reduced from X 20) 

Figure 5: A. Strong positive staining for inhibin alfa. B. Positive staining for vimentin in stroma and negative staining 

for vimentin in tubular structure. (H&E, reduced from X40) 

78


Asıf Yıldırım, et al 

Neonatal mixed sex-cord stromal tumor of the testis: a case report 

DISCUSSION 

On microscopic examination granulosa cell 

tumors contain granulose-like cells that line a 

cystic space, which is intermixed with solid 

nodular areas. These tumors can be reliably 

differentiated from yolk sac tumors because they 

demonstrate positive immunostaining with inhibin 

and negative immunostaining with AFP. 1,3,4 

Microscopically, sertoli cell tumors consist of an 

interlacing network of loose fibrous stroma with a 

cellular parenchyma composed of moderately 

small cells with irregular hyperchromatic nuclei. 2,3 

According to a recent report from the Prepubertal 

Testis Tumor Registry (1980-2001), of the 43 

registered cases of stromal tumors, 8 were mixed 

or undifferentiated stromal tumor. 3 Interpretation 

of tumor markers in neonates and infants is 

difficult. In a recent report average AFP for a fullterm 

newborn was 48.406 ng/ml. This value 

decreases to less than 8.5 ng/ml by age 8 months 4 . 

The data in the registry confirm that the vast 

majority of stromal tumors are benign. No patient 

with leydig cell, juvenile granulosa cell or sertoli 

cell tumor had metastatic disease during an 

average 24.6 months of followup. 3 However, in 

the literature at least 4 malignant sertoli cell 

tumors have been reported in prepubertal 

patients. 3 Juvenile granulosa cell tumor (JGCT) is 

a distinct variety of gonadal sex-cord stromal 

tumor that has most often reported in the ovaries 

of premenarchal girls, rarely in adults, and only 

recently in the infantile testis. 5 The first case of 

JGCT of the infantile testis was reported by 

Crump in 1983.6 Subsequently, Lawrence et al 

described 14 cases and established this tumor as a 

distinct clinicopathologic entity. 4 The 

immunohistochemical profile of ovarian sex cordstromal 

tumors has been well characterized, but 

few studies have detailed the immunophenotype 

of the corresponding testicular neoplasms. 7 

Inhibin is a peptide hormone that is produced by 

ovarian granulosa cells and testicular sertoli cells 8 . 

McCluggage et al found inhibin to be a good 

marker of testicular sex cord-stromal tumors. 7 

Similar to previous studies, the tumor exhibited 

strong positive staining for inhibin and vimentin 

in the present case. 8 

Management of sex cord-stromal testis tumors is 

still debated, since the rarity of such tumors 

makes it difficult to develop a consensus on a 

standardized approach. 

CONCLUSION 

Stromal testis tumors are rare. Data from the 

Prepubertal Testis Tumor Registry confirm the 

benign behavior of most of these tumors. Periodic 

follow-up of the remaining testicle through 

puberty and self-examination thereafter seem 

reasonable. 

REFERENCES 

1. Uehling DT, Smith JE, Logan R and Hafez GR. 

Newborn granulosa cell tumor of the testis. J Urol. 

1987; 138: 385-386. 

2. Emanuele C, Sara SM, Nicola F, Cristian F, Paola 

B, Dario F. Undifferentiated sex cord-stromal testis 

tumor. J Urol. 2004; 171 (6): 2375. 

3. Thomas JC, Ross JH and Kay R. Stromal testis 

tumors in children: e report from the Prepubertal 

Testis Tumor Registry. J Urol. 2001; 166: 2338- 

2340. 

4. Lawrence WD, Young RH and Scully RE. Juvenile 

granulosa cell tumor of the infant testis. A report of 

14 cases. Am J Surg Pathol. 1985; 9: 87-94. 

5. Antonio PA, Nancy J, Howard M. Juvenile 

Granulosa Cell Tumor of the Infantile Testis: 

Evidence of a dual epithelial-smooth muscle 

differentiation. Am J Surg Pathol. 1996; 20 (1): 72- 

79. 

6. Crump WD. Juvenile granulosa cell (sex cordstromal) 

tumor of fetal testis. J Urol. 1983; 129: 

1057-1058. 

7. McCluggage WG, Shanks J, Whiteside C, Maxwell 

P, Benerjee S, Biggart JD. Immunohistochemical 

study of testicular sex cord-stromal tumors, 

including staining with anti-inhibin antibody. Am J 

of Surg Pathol. 1998; 22 (5): 615-619. 

8. Merchenthaler I, Culler MD, Petrusz P, Negro- 

Viler A. Immunohistochemical localization of 

inhibin in rat and human reproductive tissues. Mol 

Cell Endocrinol. 1988; 54: 239-243. 

79

CASE REPORTS 

LENFOMA NEDENİYLE UYGULANAN RADYOTERAPİ SONRASI SEKONDER 

MALİGNİTELER-OLGU SUNUMU 

Alper Çelik 1 , Suat Kutun 2 , Turgay Fen 3 , Gülay Bilir 4 , Akın Önder 5 , Abdullah Çetin 6 

1 Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tokat, Türkiye 2 Ankara Onkoloji 

Hastanesi, 1. Genel Cerrahi Kliniği , Ankara, Türkiye 3 Ankara Onkoloji Hastanesi, Hematoloji Kliniği, 

Ankara, Türkiye 4 Ankara Onkoloji Hastanesi, Patoloji Kliniği, Ankara , Türkiye 5 Ankara Onkoloji Hastanesi 

, 1. Genel Cerrahi Kliniği , Ankara, Türkiye 6 Ankara Onkoloji Hastanesi , 1. Genel Cerrahi Kliniği , Ankara, 

Türkiye 

ÖZET 

Bu olgu sunumunda Hodgkin lenfoma tanısıyla baş-boyun bölgesine radyoterapi uygulanmasını takiben 

ortaya çıkan akciğer ve çoklu cilt kanserleri tespit edilen bir olgu sunulmuştur. Elli yaşında, Evre IA 

Hodgkin lenfoma nedeniyle mantle alanına radyoterapi verilen erkek hastada, 6 yıl sonra burun üzerinde 

bazal hücreli karsinom, sağ kulak üzerinde invaziv epidermoid karsinom ve sol infraorbital bölgede in-situ 

epidermoid karsinom tespit edildi. Cerrahi tedavi sonrası sağ aurikuler alana ve sol infraorbital sahaya lateral 

cerrahi sınırın yakın olması ve hastanın re-eksizyonu kabul etmemesi nedeniyle radyoterapi verilen olgu bir 

yıl sonra nefes darlığı şikayeti ile başvurdu. Sağ akciğer üst ve orta zonları tutan kitle tespit edilen olgunun 

bronkoskobik biyopsi sonucu Epidermoid karsinom olarak rapor edildi. Vena cava superior sendromu tespit 

edilen hastaya tekrar radyoterapi ve medikal tedavi uygulandı. Genel durumu giderek bozulan hasta 15 gün 

sonra öldü. 

Anahtar Kelimeler: Hodgkin lenfoma, radyoterapi, ikincil kanser 

SECONDARY MALIGNANCIES AFTER LYMPHOMA TREATED BY 

RADIOTHERAPY-CASE REPORT 

ABSTRACT 

We hereby describe a case of Hodgkin lymphoma treated with radiotherapy to head and neck region, who 

further developed lung and multiple skin cancers. A 50-year-old male patient with stage IA Hodgkin 

lymphoma was treated with radiotherapy to mantle zone. Six years later we detected basal cell carcinoma on 

his nose, invasive epidermoid carcinoma on his right ear, and in-situ epidermoid carcinoma on left 

infraorbital area. After surgical removal, radiotherapy was applied to right auricular area and left infraorbital 

area due to close lateral margin and the patient’s refusal for re-excision. One year later he admitted with 

dyspnea. We detected a mass involving the upper and middle zones of his right lung, and bronchoscopic 

biopsy revealed epidermoid carcinoma. Vena cava superior syndrome was established, and he was re-treated 

with radiotherapy and medical treatment. His medical condition deteriorated, and 15 days later he died. 

Keywords: Hodgkin lymphoma, radiotherapy, secondary cancer 

GİRİŞ 

İkinci primer maligniteler indeks karsinomla aynı 

anda tanı alırlarsa simültane, indeks tümör 

tanısından sonraki 6 aylık dönemde ortaya 

çıkarlarsa senkron ve 6 aydan sonra da metakron 

karsinom olarak isimlendirilirler 1 . Bir malignite 

olgusunun ikinci primer tanısı alabilmesi için 

Warren ve Gates kriterleri 2 geliştirilmiştir: 

1) Her iki tümörün de histolojik olarak malign 

olduğu ispat edilmelidir. 

2) İki tümör arasında minimum 2 cm sağlıklı doku 

olmalıdır. Aynı lokalizasyonda olan tümörlerde 

birbirlerinden 5 yıl süre farkı olmalıdır. 

3) Metastatik hastalık ekarte edilmelidir. 


Alper Çelik 

e-mail: doktoralper@hotmail.com 

Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tokat 

80 



Alper Çelik ve ark. 

Lenfoma nedeniyle uygulanan radyoterapi sonrası sekonder maligniteler-olgu sunumu 

Bu olgu sunumu ile primer radyoterapi sonrası 

multipl kanserler nedeniyle takip ve tedavisi 

yapılan bir olguya ait tecrübemizi sizlerle 

paylaşmayı amaçladık. Olgu sunumu için 

hastadan sözel ve yazılı olarak izin alınmıştır. 

OLGU SUNUSU 

Boyun sol tarafında şişlik nedeniyle hastanemize 

başvuran 50 yaşında erkek hastanın yapılan fizik 

muayenesinde sol servikal zincirde lenfadenopati 

tespit edildi. Çiftçilik yapan hastanın diğer sistem 

muayeneleri normal idi. Tanısal amaçlı sol 

servikal lenf nodu eksizyonu uygulanan hastanın 

patoloji raporu miks selüler tip Hodgkin lenfoma 

olarak rapor edildi. Hastanemizde yapılan 

laboratuar incelemelerinde; hemogram, 

biyokimya, akciğer ve batın tomografileri normal 

idi. Özgeçmişinde sigara bağımlılığı (30 yıl süre 

ile günde yaklaşık 40 sigara) dışında önemli 

özellik yoktu. Sistemik semptomları olmayan 

hastanın kemik iliği aspirasyon ve biyopsisi 

normal olarak değerlendirildi. Evre IA kabul 

edilerek kemoterapi endikasyonu konmayan 

hastanın baş-boyun ve supradiyafragmatik 

bölgelere Mantle tekniği ile 6 MV foton ile 200 

cGy/ gün mediasten, supraklaviküler, aksilla ve 

boyun ışınlaması (boyun 4200 cGy, mediasten 

3800 cGy) ve bir ay sonra paraaortik ve splenik 

sahalara 15 MV foton ile 3600 cGy proflaktik 

radyoterapi uygulandı. Ondört ay boyunca 

takipleri sorunsuz seyreden hastanın bu 

dönemdeki kontrolünde yaklaşık 6 ay önce 

başlayan sağ kulak üzerinde, sol infraorbital 

bölgede ve burun sırtında üzeri skuamlı, 

hiperpigmente, makülopapüler lezyonlar tespit 

edildi. Burun üzerindeki ve sol infraorbital 

sahadaki lezyonlarına eksizyonel, sağ kulak 

üzerindeki lezyonlarına insizyonel biyopsi 

uygulanan hastanın burun üzerindeki lezyon Bazal 

Hücreli Karsinom, sağ aurikula üzerindeki lezyon 

invaziv Epidermoid Karsinom ve sol infraorbital 

bölgedeki lezyon ise in-situ Epidermoid Karsinom 

olarak rapor edildi (Resim 1-2-3). Burun 

üzerindeki ve sol infraorbital sahadaki 

lezyonlarının cerrahi sınırları negatif olarak 

bildirilen hastaya sağ aurikula üzerindeki lezyon 

nedeniyle, hastanın da onayı alınarak sağ 

auriküler parsiyel eksizyon uygulandı (Resim 4). 

Adjuvan kemoterapi endikasyonu konmayan 

hastanın sol infraorbital sahadaki lezyonuna 

yönelik lateral cerrahi sınıra yakın (1 mm) olması 

ve hastanın re-eksizyonu kabul etmemesi 

sebepleriyle 6 MeV elektronla 300 cGy/gün x 17 

fraksiyonda toplam 5100 cGy radyoterapi 

uygulandı. Akciğer tomografisi radyoterapiye 

bağlı değişiklikler dışında normal olan ve 

poliklinik takibine alınan hasta 1 yıl sonra nefes 

darlığı nedeniyle başvurdu. Fizik muayenesinde 

ortopne saptanan hastanın sağ akciğer üst ve orta 

zonlarda solunum sesleri alınamadı. Göğüs 

bölgesinde Vena cava superior sendromu ile 

uyumlu kollateraller ve pletorik görünüm 

saptandı. Akciğer grafisinde sağ akciğer üst ve 

orta zonlarda konsolidasyon alanları ve bilateral 

plevral efüzyon saptanan hastanın akciğer 

tomografisinde sağ hilusta ana bronşu ve segment 

bronşlarını çevreleyerek daraltan düzensiz sınırlı 

kraniokaudal boyutu yaklaşık 6 cm, vena kava 

superior ve pulmoner arterden sınırları net ayırt 

edilemeyen kitle saptandı (Resim 5). Fiberoptik 

bronkoskopi’de sağ ana bronş girişinden itibaren 

başlayıp üst lob girişini tama yakın kapatan, üst 

lob-orta lob ayrım karinasını obstrükte eden 

infiltratif lezyon saptandı. Bronkoskopik biyopsi 

sonucu epidermoid karsinom olarak rapor edilen 

hastanın, bronkoskopik biyopsi materyalinin 

yüzey epitel ile ilişkisi olmaması nedeniyle primer 

veya metastatik tümör ayrımı yapılamadı. Acil 

radyoterapi endikasyonu konulan hastanın daha 

önce mediasten ışınlaması ve medulla spinalis 

dozları da dikkate alınarak 15 MV foton ile, ilk 

gün şiddetli dispnesi olması sebebiyle 400 

cGy’den kitle ve mediastene yönelik olarak, daha 

sonraki tedavisi oblik alanlardan planlanan 

hastaya iki gün daha 300 cGy/gün olmak üzere 

toplam 1000 cGy (Biyolojik eşdeğer doz = 1200 

cGy) palyatif radyoterapi verildi. Sonraki 

takiplerinde plevral efüzyonu artan hastaya 

torasentez, diüretik ve kortikosteroid tedavisi de 

uygulandı. Ancak, hasta 15 gün sonra respiratuvar 

arrest nedeniyle vefat etti. 

Resim 1: Bazal hücreli karsinom. Periferal palizatlanmanın 

eşlik ettiği tipik nodüler görünüm 

81




Resim 2: Belirgin nükleollü, geniş yuvarlak nükleuslu atipik 

epitelyal hücrelerin oluşturduğu iyi diferansiye epidermoid 

karsinom. 

Resim 4: Parsiyel aurikuler eksizyon sonrası görünüm. 

Resim 3: Tüm epitel katlarını tutan atipi, parakeratozis, 

anormal mitotik aktivite ve bozulmuş maturasyon paterni 

gösteren in-situ epidermoid karsinom. 

TARTIŞMA 

Malignite hastalarında uygulanan multimodaliter 

tedavilerin sağkalımı artırmasına paralel olarak 

hastaların küçümsenmeyecek bir bölümünde 

ikincil kanserler ortaya çıkmaktadır. Radyoterapi 

ve kemoterapinin mutajen ve karsinojenleri 

tetikleyerek ikincil karsinomların patogenezinde 

rol oynayabildikleri gösterilmiştir 3 . 

Özellikle çocukluk çağı maligniteleri, serviks 

kanseri, Hodgkin lenfoma ve meme kanseri 

nedeniyle radyoterapi uygulaması, ayrıca kemik 

Resim 5: Sağ akciğerdeki kitlenin tomografik görünümü. 

iliği transplantı sonrası tüm vücut ışınlaması 

sonrası sekonder kanserlerin gelişebildiği ifade 

edilmiştir. Radyoterapi sonrası ortaya çıkan 

sekonder tümörler iki ayrı grupta 

incelenmelidirler. Birinci grup özellikle yüksek 

doz radyoterapiye maruz kalan sahalarda ortaya 

çıkan sarkomlar veya sarkomatoid tümörlerdir. 

İkinci grubu ise primer radyoterapi alanından uzak 

organ veya dokularda ortaya çıkan tümörler 

oluştururlar. Radyoterapi sonrası ikincil kanser 

gelişimi ilgili en geniş iki araştırma serviks ve 

prostat kanserli hastalar üzerinde yapılmıştır. 

82




Serviks kanserli hastalarda radyoterapi 

uygulanmayan hastalarla karşılaştırıldığında 

özellikle lösemi riskinde küçük bir artış olduğu 

ifade edilmiş, bunun yanı sıra rektum, mesane, 

vajen ve kemik tümörlerinin sıklığında artış 

olduğu, daha da önemlisi radyoterapi alanından 

uzak olan mide malignitelerinin de özellikle 1 Gy 

ve üzerinde dozlarda sıklığının arttığı 

belirtilmiştir 4 . Diğer çalışmada prostat kanseri 

nedeniyle radyoterapi alan hastalar sadece cerrahi 

tedavi uygulanan hastalarla karşılaştırılmış ve 

mesane, rektum tümörlerinin yanı sıra özellikle 

sarkom sıklığında artış olduğu bildirilmiştir 5 . 

İkincil karsinom sıklığı baş ve boyunda lokalize 

yassı epitel hücreli kanserlerde % 5-36 arasında 

değişmektedir 6 . Farklı nedenlerle radyoterapi 

uygulanan saha ve çevresinde osteosarkom 7, 

anjiosarkom 8 ve bazal hücreli karsinomların 9 

gelişebildiği bildirilmiştir. 

Hodgkin lenfoma nedeniyle alkilleyici ajan 

kullanımı lösemi riskini artırmaktadır. Alkilleyici 

ajanların yanı sıra radyoterapi uygulanması lösemi 

riskinde ilave bir artışa neden olmamakla birlikte 

meme, akciğer, kemik, tiroid, mide ve cilt 

tümörlerinin görülme riskini artırmaktadır. Meme 

ve tiroid kanserleri için genellikle 15 yıllık bir 

latent period gerekli olmakla beraber akciğer 

kanserlerinin tedaviden sonraki 5 yıllık dönemde 

dahi ortaya çıkabileceği iddia edilmiştir 3,10,11 . 

Lorigan ve ark. çalışmasında Hodgkin lenfoma 

tedavisi almış hastalarda akciğer kanseri gelişme 

için 2.6-7 kat artmış relatif risk olduğu, bu riskin 

tedaviden sonra geçen süre ile anlamlı artış 

gösterdiği ve 45 yaşın üzerinde tedavi gören hasta 

grubunda anlamlı artış olduğu belirtilmiştir. Bir 

diğer önemli nokta ise kemoterapi ile 

radyoterapinin additif etki gösterdiği ve sigara 

kullanımının bu riski daha da artırdığı gerçeğidir 

12 . İonizan radyasyon-akciğer kanseri ilişkisi pek 

çok çalışmada vurgulanmıştır. Hatta ionizan 

radyasyon dozuna göre sekonder akciğer kanseri 

gelişme riskinin belirlenebileceği dahi iddia 

edilmiştir 

13 . Bir diğer araştırmada ionizan 

radyasyon tedavisi alan hastalarda 40 Gy ve 

üzerinde radyoterapi dozlarında sekonder akciğer 

kanseri riskinde anlamlı artış olduğu, daha düşük 

dozlarda da artış olmakla beraber istatistiki 

anlamlılık olmadığı ve sekonder akciğer kanseri 

gelişme riskinde her Gy başına %0.15 artış olduğu 

bildirilmiştir 14 . Gilbert ve ark. çalışmasında da 

ikincil akciğer kanserlerinin %79.5’inin 

radyoterapi tedavi alanı içinde olduğu, 

%19.2’sinin daha düşük dozlarda radyoterapi alan 

sahalarda ve hatta %17.3’ünün tedavi sahası 

dışında geliştiğini bildirmişlerdir 15 . Sachs ve 

Brenner’in çalışmasında 3 Gy ve daha düşük 

dozlarda radyoterapiye bağlı ortaya çıkan ikincil 

kanserlerin özellikle atom bombası sonrası 

Japonya kaynaklı araştırmalar sebebiyle iyi 

bilindiği, ancak yüksek doz radyoterapiye bağlı 

ikincil kanserlerin daha yeni bir konu olduğu 

vurgulanmıştır. Önceden yüksek doz RT alan 

hastalarda bu bölgede ciddi bir hücre ölümü 

meydana geldiği ve bu sahalardan kanser 

gelişemeyeceği düşüncesi hâkim idi. Ancak adı 

geçen çalışmayla gösterilmiştir ki, hücre ölümü 

gerçekleşen sahalara radyasyondan etkilenen 

organdaki kök hücreler migrate olmaktadırlar. 

Kök hücrelere ait bu migrasyon ve proliferasyona 

repopülasyon adı verilmiştir. Nekrotik saha ve 

periferindeki hücre repopülasyonu bu sahalarda 

gelişen ikincil malignitelerden sorumlu 

tutulmuştur. Re-popülasyon adı verilen hücre 

kinetiği yüksek doz RT uygulanan sahalardaki 

ikincil kanser olasılığını matematiksel olarak 

belirleyebilme olanağını da sağlar 16 . 

Melanom Dışı Cilt Kanserleri (MDCK) için hem 

UV hem de ionizan radyasyon risk faktörüdür 17 . 

Radyasyonun en önemli özelliği lokal olarak 

biyolojik önemi olan kimyasal bağları 

parçalayabilecek güçte büyük miktarlarda enerji 

açığa çıkarmasıdır. Karsinogenezde önemli olan 

iyonize radyasyon, başlıca elektromanyetik x- 

ışınları, gama ışınları ve elektron, proton, alfa 

partiküller ve ağır iyonlar gibi yüklü olanlar ve 

nötronlar gibi yüksüz olan partiküllü ışınlardır. 

Pek çok merkez tarafından MDCK hem sık 

görüldüklerinden hem de sağkalım özellikle erken 

evrelerde iyi olduğundan veritabanı kaydı 

tutulmamaktadır. Bu yaklaşım konu hakkındaki 

edinimlerimizin genellikle kişisel veya kurumsal 

tecrübe ve bilgi birikimi ile sınırlı kalmasına yol 

açmaktadır. Perkins’in çalışması çok merkezli bir 

çalışma olması sebebiyle bu konuda üzerinde 

durulması gereken bir çalışmadır. Çocukluk 

çağında malignite nedeniyle %90’ı RT almış 

13132 hasta üzerinde yapılan çalışmada 213 

olguda MDCK tespit edilmiş olup, bu olguların 

yaklaşık %10’luk bölümünde ortaya çıkan cilt 

kanserlerinin RT alanının dışında olduğu ve 

radyasyon tedavisi almış olmanın MDCK riskini 

normal popülasyona göre 6.3 kat arttırdığı 

bildirilmiştir 17 . Bir diğer araştırmada daha önce 

MDCK dışı hastalıklar nedeniyle RT almış 

hastalarda Bazal Hücreli Karsinom (BHK) 

sıklığında anlamlı artış saptanmış, Yassı Hücreli 

Karsinom (YHK) sıklığında da artış saptanmış 

ancak bu artış istatistiksel anlamlılığa 

ulaşmamıştır 18 . 

83




Ultraviole radyasyon tipinin cilt kanseri sıklığı 

üzerine olan etkisinin araştırıldığı bir çalışmada 

psöriazis nedeniyle Psöralen + Ultraviole A (UV- 

A) tedavisi gören hastalarda özellikle YHK 

sıklığında anlamlı artış saptanmıştır. Ancak, bu 

hastalarda zaten cilt duyarlılığı ve cilt yapısı 

nedeniyle YHK’a yatkınlık olduğu göz önünde 

bulundurulmalıdır 19 . Bizim hastamızda da benzer 

bir cilt duyarlılığı söz konusu olmasına rağmen 

sol infraorbital sahadaki lezyona lateral cerrahi 

sınırın yakın olması ve hastanın re-eksizyonu 

kabul etmemesi sebebiyle adjuvan radyoterapi 

uygulandı. 

Sunduğumuz olguda ikincil akciğer kanseri 

Hodgkin lenfoma tanısından 7 yıl sonra ortaya 

çıktı. Ancak hastamızın kemoterapi almamış 

olması ve sigara bağımlısı olması akciğer 

kanserinin radyoterapiye sekonder olmaması 

ihtimalini kuvvetlendirmektedir. Hastamızın çiftçi 

olması ve uzun süre güneşe maruz kalmış olması 

da tek başına önemli bir risk faktörüdür. Ayrıca, 

cilt kanseri ile akciğer kanserinin aynı histolojik 

tipte olması ve bronkoskobik materyalde yüzey 

epitel ile ilişkinin gösterilememiş olması da 

akciğer kanserinin orijininin belirlenmesini 

güçleştirmektedir. Eğer, akciğer kanseri ile cilt 

kanserinin farklı Grade’e sahip oldukları veya 

akciğer kanserinde in-situ komponent varlığı 

gösterilebilmiş olsaydı primer akciğer kanseri 

tanısı konulabilirdi 

20 . Hastamızda genetik 

predispozisyon varlığı araştırılmadı. Ancak 

akciğerde lokalize malignitelerde, primer veya 

metastatik tümör ayrımında immünhistokimyasal 

yöntemlerden, özellikle sitokeratin boyalarından 

yararlanılarak, hastamızın tedavisinde farklı yollar 

izlenilebilirdi. Bu bağlamda ikincil tümör şüphesi 

olan olgularda İnce İğne Aspirasyon Biyopsisi 

(İİAB) gibi tanısal yöntemlerden ziyade dokunun 

yüzey epitel veya sağlam doku ile ilişkisi 

gösterilerek, indeks tümörle ikincil tümör arasında 

Grade farklılığı veya ikincil tümörde in-situ 

komponent varlığının ortaya konmasının 

metastazın ekarte edilerek, ikincil tümör tanısının 

konmasında en önemli yaklaşım olduğunu 

düşünmekteyiz. 

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85

CASE REPORTS 

TWO NEW KABUKI CASES OF KABUKI MAKE-UP SYNDROME 

ABSTRACT 

Ahmet Sert, Mehmet Emre Atabek, Özgür Pirgon 

Selçuk Üniversitesi Meram Tıp Fakültesi, Pediatrik Endokrinoloji, Konya, Türkiye 

Kabuki syndrome (Kabuki make-up syndrome, Niikawa–Kuroki syndrome) is a multiple congenital 

anomaly/mental retardation syndrome. We report on an 11-month-old girl with Kabuki make-up syndrome 

who has premature telarche, premature pubarche and epilepsy, and a 4-month-old boy with Kabuki make-up 

syndrome who had been operated due to diaphragmatic hernia and had mesocardia confirmed by 

echocardiography. In the study, we emphasize that careful phenotypic examination of children should be 

performed in every patient presenting with mental retardation and epilepsy to diagnose Kabuki syndrome 

and the patients diagnosed as Kabuki syndrome should be followed for precocius puberty. We suggest that 

mesocardia, which has not been reported in the literature yet, may be considered as one of the cardiological 

findings of Kabuki syndrome and all Kabuki patients should be evaluated for life-threatening complications 

of congenital diaphragmatic hernia. 

Keywords: Diaphragmatic hernia, epilepsy, Kabuki syndrome, premature telarche 

ÖZET 

KABUKİ MAKE-UP SENDROMUNUN İKİ YENİ VAKASI 

Kabuki sendromu (Kabuki make-up sendromu, Niikawa-Kuroki sendromu) çoklu doğumsal anomali/mental 

gerilik sendromudur. Epilepsi, prematür telarş ve prematür pubarşı olan Kabuki make-up sendromlu 11 aylık 

kız ve ekokardiyografi ile mezokardisi doğrulanan ve diyafragma hernisi nedeniyle opere edilen Kabuki 

make-up sendromlu 4 aylık erkek çocuğu sunuyoruz. Mental gerilik ve epilepsi ile prezente olan her hastada 

dikkatli fenotipik inceleme yapılması gerektiğini ve Kabuki sendromu teşhisi konulan hastaların erken 

puberte için takip edilmesi gerektiğini vurguluyoruz. Bunun yanında, henüz literatürde bildirilmeyen 

mezokardinin Kabuki sendromunun kardiyolojik bulgularından birisi olarak dikkate alınabileceğini ve 

Kabuki sendromlu bütün hastaların doğumsal diyafragma hernisinin yaşamı tehdit eden komplikasyonları 

için değerlendirilmesi gerektiğini öneriyoruz. 

Anahtar Kelimeler: Diafragma hernisi, epilepsi, Kabuki sendromu, prematür telarş 

INTRODUCTION 

Kabuki syndrome (Kabuki make-up syndrome, 

Niikawa–Kuroki syndrome) is a multiple 

congenital anomaly/mental retardation syndrome 

that was first described simultaneously by two 

groups in Japan, Niikawa et al. 1 and Kuroki et al. 2 . 

The prevalence of Kabuki syndrome in the 

Japanese population has been estimated to be 

1/32,000 3 . The designation Kabuki make-up refers 

to the resemblance of the facial features with the 

characteristic make-up used by actors of Kabuki, a 

traditional Japanese theatrical form 1 . Premature 

telarche, premature pubarche and epilepsy 

association with Kabuki make up syndrome have 

been rarely reported in the literature 4 . 

Diaphragmatic defect is an uncommon finding in 

Kabuki syndrome, reported in only two female 

patients with a diaphragmatic eventration 5 and in 

an aborted fetus with a diaphragmatic hernia 6 . 

Mesocardia accompanied by Kabuki syndrome in 

the literature has not been reported yet. We report 

on an 11-month-old girl with Kabuki make up 

syndrome who has premature telarche, premature 

pubarche and epilepsy, and a 4-month-old boy 

with Kabuki make up syndrome who has 

mesocardia and diaphragmatic hernia. 


Ahmet Sert 

e-mail: ahmetsert2@hotmail.com 

Selçuk Üniversitesi Meram Tıp Fakültesi, Pediatrik Endokrinoloji, Konya, Türkiye 

86 



Ahmet Sert, et al 

Two new kabuki cases of kabuki make-up syndrome 


Case 1 

An 11-month-old girl was referred to emergency 

clinics for diarrhea and vomiting. She was born by 

cesarean section due to breech presentation after a 

term gestation to a primigravida mother. The 

parents were healthy first-degree cousins. She had 

psychomotor developmental delay and seizures at 

ten months of age. However, the breast 

development was tanner stage 2 at 4 months of 

age. The pubic hair was tanner stage 2 at 9 months 

of age. Her height was 69 cm (50-75 p), weight 

7.3 kg (3-10 p) and head circumference 40 cm (< 

3 percentile). She had facial dysmorphism with 

high arched eyebrows sparse laterally, long 

palpebral fissures with everted lower eyelids, long 

eyelashes accompanying microcephaly. Her nose 

was broad with depressed tip, and ears were 

prominent and protruding (Fig. 1). On oral 

examination she had high arched palate. She had a 

generalized hypotonia. She had both premature 

telarche and premature pubarche. The other 

system findings were normal. During one hour 

follow up, generalized afebrile tonic-clonic 

seizures, lasting longer than 30 min were 

observed. The status epilepticus was well 

controlled by an appropriate treatment. On 

admission biochemical investigations, including 

serum electrolytes, liver function tests, lipid 

profiles, and coagulation tests were all within 

normal limits except for presence of leukocytosis 

(28.1X10 9 /L) in the complete blood count. The 

electroencephalography and magnetic resonance 

imaging of the brain and pituitary region were 

normal as well as abdomen and pelvic 

ultrasonography, and echocardiographic 

examination. Ophthalmologic examination 

revealed normal findings. Bone age was at six 

months girl. Gonadotrophin releasing hormone 

test was performed to rule out the presence of 

precocious puberty revealed an exaggerated 

follicle stimulating hormone response and 

prepubertal level of luteinizing hormone response. 

She was diagnosed as Kabuki syndrome due to 

her clinical findings. Testing of three consecutive 

stool specimens showed Entamoeba histolytica as 

the causative agent for the diarrhea and vomiting. 

Stool cultures were negative for other 

enteropathogens. The patient was treated 

successfully by metronidazole. She improved 

clinically during her stay at the hospital, and was 

discharged in 10 days. 

Figure 1: An 11 months old girl showing facial dysmorphism 

typical for Kabuki syndrome with long palpebral fissures, 

arched eyebrows sparse laterally, epicanthic folds, and 

premature telarche. 

Case 2 

A 4-month-old boy was referred to pediatric 

endocrinology division to be evaluated for facial 

dysmorphism. He was born to a normal pregnancy 

by vaginal delivery. His birth weight was 2700 g. 

His parents were healthy and nonconsanguineous. 

There was no family history for 

mentally retarded persons nor individuals with 

congenital anomalies. Immediately after birth, he 

had been diagnosed as having diaphragmatic 

hernia and was intubated by endotracheal tube. At 

3 days of age, a surgical operation for an anterior 

diaphragmatic hernia through the foramen of 

Morgagni was performed. He had been followed 

by mechanic ventilation for 25 days in the 

newborn intensive care unite, and antibiotic 

therapy was administered for sepsis during 

follow-up. At 4 months of age, physical 

examination revealed his height as 64.5 cm (50 p), 

weight 4500 g (3 p) and head circumference 37.6 

cm (< 3 p). He was noted to have facial 

dysmorphic features—long palpebral fissures with 

eversion of the lower lateral eyelids, arched 

eyebrows with lateral sparseness, depressed nasal 

tip, large, prominent and cupped ears (Fig. 2). 

87




In addition to the distinct facial features, he also 

had high arched palate, persistent fetal finger 

pads, arachnodactyly, bilateral simian line and 

umblical hernia. Cardiac examination revealed no 

significant murmurs. The other system findings 

were normal. Laboratory examinations were 

within normal limits. Chest radiography showed 

no cardiac enlargement. Echocardiography 

demonstrated mesocardia with no other associated 

cardiac anomalies. He was diagnosed as Kabuki 

make up syndrome due to clinical findings. 

Figure 2: Male patient showing facial dysmorphic features 

suggestive for Kabuki make-up syndrome. 

DISCUSSION 

Kabuki make-up syndrome was established with 

clinical findings in both patients. Currently, there 

is no consensus on the diagnostic criteria for 

Kabuki syndrome and there is no clinically 

available genetic test to confirm the diagnosis. In 

1988, Niikawa et al. reported on the clinical 

findings in 62 patients diagnosed with Kabuki 

syndrome. Based on the findings in these patients, 

five cardinal manifestations were defined. These 

included a ‘peculiar face’ (eversion of the lower 

lateral eyelid, arched eyebrows with the lateral 

one-third dispersed or sparse, depressed nasal tip, 

and prominent ears) in 100% of their patients, 

skeletal anomalies (deformed spinal column with 

or without sagittal cleft vertebrae, and 

brachydactyly V) in 92% of their patients, 

dermatoglyphic abnormalities (fingertip pads, 

absence of digital triradius c and/or d, and 

increased digital ulnar loop and hypothenar loop 

patterns) in 93% of their patients, mild to 

moderate mental retardation in 92% of their 

patients, and postnatal growth deficiency in 83% 

of their patients. There have also been a number 

of less frequent findings reported in Kabuki 

syndrome, including visceral abnormalities, 

premature breast development in females, and 

susceptibility to frequent infections 3,7 . Tutar et al. 

reported the first non-Japanese Asian case with 

Kabuki make up syndrome who had premature 

thelarche from Turkey 8 . In our study, the female 

patient had premature telarche and serious 

infection was established in the boy. The 

dysmorphic features of our patients are in 

accordance with detailed clinical findings 

observed in Kabuki patients. 

Although diagnosis relies on dysmorphic features, 

neurological symptoms are the most invalidating 

manifestations in the Kabuki syndrome clinical 

spectrum, often presenting as the first complaint; 

nevertheless, Kabuki syndrome is still a rare 

diagnoses at neurology clinics 4 . Neurological and 

endocrinological anomalies that are reported to 

include neonatal hypotonia, feeding problems, 

seizures, West syndrome, microcephaly, brain 

atrophy, growth hormone deficiency, precocious 

puberty, hypoglycemia, delayed sexual 

development, and diabetes insipidus. Other 

neurological abnormalities observed are 

subatrophy of the optic nerves, subarachnoid cyst, 

cerebellar and brainstem atrophy, and epilepsy 

2,9,10 . In accordance with the literature, the female 

patient presented with developmental delay and 

seizures. On the other hand she also had 

microcephaly. Schrander-Stumpel et al. reported 

29 Caucasian patients and reviewed 60 Japanese 

and 29 non-Japanese patients, noting that non- 

Japanese patients with this syndrome had more 

marked neurological symptoms. In over 80% of 

non-Japanese patients, neurological symptoms 

were a major clinical problem 11 . Precocious 

puberty is an occasional finding in the syndrome. 

Early breast development was noted in 7 of 31 

female Japanese patients. Endocrine studies in 5 

cases demonstrated markedly elevated plasma 

follicle-stimulating hormone and moderately high 

prolactin levels 3 . Bereket et al. reported that the 

diagnosis of Kabuki syndrome should be 

considered in patients with hypoglycemia or 

premature thelarche when associated with 

developmental delay and a peculiar facies 10 . The 

girl patient did not have precocious puberty but 

had markedly elevated plasma follicle-stimulating 

hormone levels which is consistent with literature 

data. 

88




Diaphragmatic defects have been reported 

previously in only five patients with Kabuki 

syndrome. Bilateral eventration of the diaphragm 

was reported in two Kabuki syndrome patients 5 . 

Diaphragmatic defects were prenatally diagnosed 

in a fetus of a mother with minor facial anomalies 

of Kabuki syndrome and a previous child with 

Kabuki syndrome 6 . A partial defect of the right 

diaphragm with herniation of the liver into the 

thorax was present in a fourth patient 12 . Recently, 

a fifth patient with diaphragmatic hernia was 

reported 13 . The male patient supports the previous 

suggestion that Kabuki syndrome should be added 

to the list of syndromes rarely associated with 

diaphragm defects. 

In recent studies, it has been reported that 

congenital heart defect is present in 58% of 

patients with Kabuki syndrome 14 . The most 

common finding appears to be juxtaductal 

coarctation of the aorta, a relatively rare heart 

defect, followed by VSD and ASD 15 . To the best 

of our knowledge, a patient with mesocardia in 

Kabuki make up syndrome hasn’t been reported 

yet and our patient will be the first ever reported. 

In conclusion, careful dysmorphological 

examination should be performed in all patients 

presenting with mental retardation and epilepsy to 

diagnose Kabuki syndrome. The patients 

diagnosed as Kabuki syndrome should be 

followed for premature telarche and precocious 

puberty. Furthermore, we suggest that mesocardia 

should be kept in mind as a cardiological finding 

of Kabuki syndrome, and all cases should be 

evaluated for life-threatening anomalies such as 

congenital diaphragmatic hernia and its 

complications. 

REFERENCES 

1. Niikawa N, Matsuura N. Kabuki make-up 

syndrome: a syndrome of mental retardation, 

unusual facies, large and protruding ears, and 

postnatal growth deficiency. J Pediatr 1981; 

99:565–569. 

2. Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I. A 

new malformation syndrome of long palpebral 

fissures, large ears, depressed nasal tip, and skeletal 

anomalies associated with postnatal dwarfism and 

mental retardation. J Pediatr 1981; 99:570–573. 

3. Niikawa N, Kuroki Y, Kajii T, et al. Kabuki makeup 

(Niikawa–Kuroki) syndrome: a study of 62 

patients. Am J Med Genet 1988; 31:565–589. 

4. Di Gennaro G, Condoluci C, Casali C, Ciccarelli O, 

Albertini G. Epilepsy and polymicrogyria in 

Kabuki make-up (Niikawa-Kuroki) syndrome. 

Pediatr Neurol 1999; 21:566-568. 

5. Silengo M, Lerone M, Seri M, Romeo G. 

Inheritance of Niikawa- Kuroki (Kabuki make-up) 

syndrome. Am J Med Genet 1996; 66:368. 

6. Philip N, Meinecke P, David A, et al. Kabuki 

make-up (Niikawa- Kuroki) syndrome: a study of 

16 non-Japanese cases. Clin Dysmorph 1992; 1:63– 

77. 

7. Kawame H, Hannibal C, Hudgins L, Pagon RA. 

Phenotypic spectrum and management issues in 

Kabuki syndrome. J Pediatr 1999; 134: 480–485. 

8. Tutar HE, Ocal G, Ince E, Cin S. Premature 

thelarche in Kabuki make-up syndrome. Acta 

Paediatr Jpn 1994; 36(1):104-106. 

9. Kasuya H, Shimizu T, Nakamura S, Takakura K. 

Kabuki make-up syndrome and report of a case 

with hydrocephalus. Child’s Nerv Syst 1998; 

14:230–235. 

10. Bereket A, Turan S, Alper G, Comu S, Alpay H, 

Akalin F. Two patients with Kabuki syndrome 

presenting with endocrine problems. J Pediatr 

Endocrinol Metab 2001; 14(2):215-20. 

11. Schrander-Stumpel C, Meinecke P, Wilson G, et al. 

The Kabuki (Niikawa-Kuroki) syndrome: further 

delineation of the phenotype in 29 non-Japanese 

patients. Eur J Pediatr 1994; 153:438–445. 

12. Tsukahara M, Kuroki Y, Imaizumi K, Miyazawa Y, 

Matsuo K. Dominant inheritance of Kabuki makeup 

syndrome. Am J Med Genet 1997; 73:19–23. 

13. Donadio A, Garavelli L, Banchini G, Neri G. 

Kabuki syndrome and diaphragmatic defects: a 

frequent association in non-Asian patients? Am J 

Med Genet 2000; 91:164-165. 

14. Digilio MC, Marino B, Toscano A, Giannotti A, 

Dallapiccola B. Congenital heart defects in Kabuki 

syndrome. Am J Med Genet 2001; 100:269-274. 

15. Hughes HE, Davies SJ. Coarctation of the aorta in 

Kabuki syndrome. Arch Dis Child 1994; 70:512– 

514. 

89

REVIEW 

IS THERE A “HIDDEN HIV/AIDS EPIDEMIC” IN TURKEY?: THE GAP BETWEEN 

THE NUMBERS AND THE FACTS 

Pınar Ay 1 , Selma Karabey 2 

1 Marmara Üniversitesi Tıp Fakültesi, Halk Sağlığı Anabilim Dalı, İstanbul, Türkiye 2 İstanbul Üniversitesi 

İstanbul Tıp Fakültesi, Halk Sağlığı Anabilim Dalı, İstanbul, Türkiye 

ABSTRACT 

Since the number of persons living with HIV/AIDS was relatively low compared to the hard-hit countries, 

HIV/AIDS was not considered as an emerging health problem in Turkey. However Turkey carries a number 

of factors which enable the spread of HIV/AIDS and the reported rates are accepted to be an underestimation 

due to the drawbacks of the present surveillance system. This paper discusses the epidemiology of 

HIV/AIDS in Turkey, factors influencing risk and prevention and the need concerning prevention and 

control activities in order to address future challenges to combat the epidemic. 

Keywords: HIV/AIDS, Turkey, epidemiology, prevention, control 

TÜRKİYE’DE GİZLİ SEYREDEN BİR HIV/AIDS SALGINI MI VAR?: SAYILAR VE 

GERÇEKLER ARASINDAKİ FARKLILIKLAR 

ÖZET 

Türkiye’de HIV/AIDS’in öncelikli sağlık sorunları arasında sayılmaması, olgu sayılarının bu hastalık 

tarafından vurulan diğer pek çok ülkeye kıyasla göreceli olarak düşük olmasından kaynaklanmaktadır. Ancak 

Türkiye’nin HIV/AIDS’in yayılımını kolaylaştıran pek çok risk faktörünü barındırdığı ve bildirilen olgu 

sayılarındaki düşüklüğün sürveyans sistemindeki yetersizliklere bağlı olduğu kabul edilmektedir. Bu 

makalede, HIV/AIDS epidemisi ile mücadele ederken yapılması gerekenleri ortaya koymak amacıyla 

Türkiye’deki hastalık epidemiyolojisi, riski etkileyen faktörler, önleme ve kontrol etkinlikleriyle ilgili 

gereksinimler tartışılmaktadır. 

Anahtar Kelimeler: HIV/AIDS, Türkiye, epidemiyoloji, önleme, kontrol 

INTRODUCTION 

HIV/AIDS is considered as one of the most 

devastating disease of the recent decade due to its 

high morbidity, mortality and economic impact. 

As for December 2004, it is estimated that a total 

of 39.4 million people worldwide carry the HIV 

virus 1 . The epidemic has been growing and there 

is no region unaffected. 

Today, HIV/AIDS should be considered as an 

emerging disease for Turkey, too. According to 

the statistics of the Turkish Ministry of Health, a 

total of 1922 persons living with HIV/AIDS 

(PLHA) were notified from 1985 to December 

2004 in a population of more than 70 million. In 

the year 2004, 163 HIV and 47 AIDS cases were 

newly identified 2 . Figure 1 shows the reported 

number of PLHA in Turkey from 1985 through 

the end of 2004. 

Since the reported prevalence was relatively low 

compared to the hard-hit countries, policy- makers 

as well as the community did not consider 

HIV/AIDS as an emerging health problem in 

Turkey. However, the figures mentioned above 

are accepted to be an underestimation due to the 

drawbacks of the present surveillance system. 

Moreover, Turkey has a number of risk factors 

that enable the spread of HIV/AIDS 3 . So the aim 

of this paper is to discuss the epidemiology of 

HIV/AIDS in Turkey, factors influencing risk and 

prevention and the need concerning prevention 

and control activities in order to address future 

challenges to combat the epidemic. 


Pınar Ay 

e-mail: aypinar@hotmail.com 

Marmara Üniversitesi Tıp Fakültesi, Halk Sağlığı Anabilim Dalı, İstanbul, Türkiye 

90 



Pınar Ay, Selma Karabey 

Is there a “Hidden HIV/AIDS epidemic” in Turkey?: the gap between the numbers and the facts 

In this paper, initially the present surveillance 

system for HIV/AIDS and its limitations will be 

discussed. Subsequently, the authors will present 

the epidemiological pattern of HIV/AIDS, the 

factors which influence the risk of the country and 

the prevention-control activities which are carried 

by both the governmental and the non 

governmental organizations. Lastly, taking into 

consideration the epidemiological pattern and the 

limitations of the present prevention- control 

programs, the authors will communicate the 

strategies to tackle the problem. 

In this paper, primarily the statistics obtained from 

the Turkish Ministry of Health as well as the 

reports of UNAIDS are utilized. The authors 

retrieved all the articles cited in Pubmed through 

using the key words of “HIV/AIDS” and 

“Turkey”. The authors also made an effort to 

cover the nationally published articles relevant to 

HIV/AIDS. 

The present surveillance system and the 

drawbacks of the morbidity data 

Since 1987, serologic tests had been compulsory 

for blood and organ donors, registered sex 

workers and Turkish men who reside in foreign 

countries, but come to Turkey for their military 

services. From the year 2002 onwards, HIV 

testing was also required for couples before 

getting married. Public as well as the private 

sector, both of which are within the HIV 

surveillance system, perform HIV tests and report 

to the Ministry of Health. However sentinel sites 

do not exist within the present system. 

The major problem concerning the morbidity data 

is that testing is limited and is not systematic 

among the persons under high-risk 4 . There is no 

surveillance system targeting unregistered sex 

workers, men who have sex with men (MSM) or 

intravenous drug users (IUD). Although tests are 

performed in the public hospitals during antenatal 

examinations, this practice is also not 

implemented systematically. 

Also the number of reported cases can not be 

accepted as a sufficient indicator by itself. 

Particularly in regions with low prevalence, 

surveillance programs that evaluate behavioral 

change among vulnerable groups are needed 5 . The 

rate of condom use in commercial or casual sex or 

needle exchange should be evaluated. Yet in 

Turkey, this information is currently lacking. 

Turkish Ministry of Health reported that in the 

year 2003 nearly 2.5 million HIV tests were 

performed. Interestingly, only %0.5 of the tests 

was performed on sex workers. Commercial sex 

work is considered as the major driver of the 

epidemic in Turkey 6 . But sex workers who were 

tested for HIV are the registered ones and do not 

represent the parent population. In Turkey, there 

are approximately 2000 registered sex workers, 

but the estimated number for unregistered sex 

workers is 15 000 only for Istanbul 7 . Moreover 

after the fall of the Eastern Block, some women 

from the former Soviet Union and the East 

Europe, who come by tourist visas, work as 

commercial sex workers in Turkey. Yet the data 

about the unregistered sex workers, who might be 

at an increased risk and have decreased access to 

health services, is limited to those arrested by the 

police and to some small-scaled studies. 

Figure 1: Reported HIV Positive and AIDS Cases in Turkey (1985-2004) 2 

91




Private sector, which has been flourishing for the 

last two decades, is becoming an important health 

service provider in Turkey. Persons suffering 

from sexually transmitted infections (STIs) prefer 

the private sector since they do not want to 

disclose their diseases in a conservative 

community 8 . Another important problem with the 

morbidity data is that notification from the private 

sector is under the actual figures. 

Although a systematic and a comprehensive 

surveillance system for HIV/AIDS is not present 

in Turkey yet, there are constructive efforts in this 

direction. Recently, a project was started within 

the context of the Reproductive Health Program 

of the European Union, which aims to implement 

a sentinel surveillance system designed for STIs 

and HIV/AIDS 9 . Also in 2005, the Turkish 

Ministry of Health received a grant from the 

“Global Fund to Fight HIV/AIDS, Tuberculosis 

and Malaria” for the HIV/AIDS Prevention and 

Support Project. Within this project, a behavioral 

study targeting the vulnerable groups will be 

carried out which consequently will provide an 

important database for planning the prevention 

activities. 

The epidemiological pattern of HIV/AIDS in 

Turkey 

The epidemiological pattern of HIV/AIDS in 

Turkey is similar to the African pattern, where 

heterosexual transmission is the main route of 

spread 8 . Homo-bisexual route is the second most 

common route among male. But since 

homosexuality is still a taboo in Turkey, MSM are 

probably underreported. Although Turkey’s 

geographic location is close to the countries of 

Eastern Europe, it still shows a different pattern 

from them 8 because IDU is not as prevalent as the 

Eastern European countries. The dominant 

heterosexual route and the increasing prevalence 

among women can be expected to increase the 

vertical transmission throughout the years in 

Turkey, where antenatal HIV testing is limited 

and not systematic. 

Figure 3: Reported modes of transmission among men 10 

The factors influencing risk and prevention 

Turkey deserves special attention since it carries 

several risk factors for the spread of HIV/AIDS. 

Geographic location of the country and high 

mobility, low social and economic status as well 

as the wide gaps, gender inequalities and 

demographic structure are evaluated as important 

risk factors for HIV/AIDS 3,4,7 . Moreover, there are 

other risk factors which are mentioned by 

UNAIDS, that are important in countries of low 

prevalence 5 . Both the public and the governments 

Figure 2: Reported modes of transmission among women 10 

In Turkey, HIV positive cases show male 

dominance. Among all reported cases, the malefemale 

ratio is approximately 2.2 10 

This ratio showed a decreasing trend and women 

showed an increasing proportion throughout the 

years. Nearly 70% of the reported HIV/AIDS 

cases belong to the 15-39 year age group. The 

major mode of transmission is the heterosexual 

relationship for both sexes 10 

Figure 2 and 3 summarizes the possible routes of 

transmission for both genders. 

do not view HIV/AIDS as a priority due to the 

underreporting which leads to low number of 

cases. Therefore insufficient funds are allocated to 

this issue among the limited public health 

resources. Opinions such as “HIV can not infect 

me” or “HIV is others’ disease” are very common. 

These attitudes prevent the discussion on risky 

behavior and thus preclude the prevention 

measures building an environment enabling the 

spread of HIV. 

• Geographic location and mobility: 

Turkey is closely located to the countries that 

have an increased prevalence of HIV/AIDS. The 

92




high prevalence and the accelerated epidemic in 

Eastern Europe will have a significant impact on 

Turkey, too. The movement of commercial sex 

workers from these countries to Turkey is an 

important mode in transmission. From 1996 to 

2002, 23 500 foreigners were deported from being 

involved in illegal sex work 6 . Also trading 

activities with the neighboring countries, the 

travel of businessmen and tourism increases the 

risk 3 . 

From 1985 to 2003, 22.6% of the HIV positive 

cases that were reported had a foreign nationality. 

When we look at the countries of the origin, 

nearly 30% of the cases were from the former 

Soviet Union, about 20% are from the East 

European, 20% percent are from the African and 

more than 10% percent are from the West 

European countries 10 . Sometimes this fact is 

falsely interpreted by the community and HIV is 

perceived as if it is a disease of foreigners. 

• Social and economic inequalities: 

Socio-economic deprivation and wide inequalities 

also increase the risk of HIV/AIDS in Turkey. 

Turkey has a GNP per capita of approximately 

3300 US Dollars. But more importantly, there are 

deep inequalities within the country. Almost all 

health and educational indices vary highly from 

west to east. The knowledge and attitudes towards 

HIV/AIDS is consistent with this fact. Turkish 

Demographic and Health Survey (TDHS) which 

was conducted in 2003, determined that the 

percentage of married women who had heard of 

AIDS in the west and east region of the country 

was 92.3% and 69.1%, respectively. In the west 

region 71.2% of the women believed that 

HIV/AIDS was preventable. However in the east 

only 43.3% considered this disease as preventable. 

When education status was taken into account, the 

married women who were illiterate was the most 

susceptible group 11 . Again according to TDHS 

2003, overall 21.9% of the married women stated 

condom as one of the preventive measures. 

However among illiterate women only 5.5% 

pronounced condom as a measure 11 . 

•Gender power inequalities: 

Research has shown that gender power 

inequalities and violence against women is 

associated with inconsistent condom use and 

unplanned pregnancies 12,13 . Domestic violence is 

not rare in Turkey. In a survey, which is carried 

out among pregnant women in a province in the 

east of Turkey, the prevalence of physical or 

psychological abuse during pregnancy was 

determined as 33.3%. More than half of the 

women who were exposed to abuse had physical 

violence. Abused women had a lower level of 

education and were more likely to have unplanned 

pregnancies 14 . Also nearly 40% of women 

considered the violence used by their husband as a 

legitimatized act 11 . This finding is important in 

showing the internalization of the socially 

subordinate role of women. 

•Cultural context - beliefs and attitudes: 

Turkey was considered a traditional and mostly a 

patriarchal society. But within the recent decades, 

industrialization, urbanization, advances in 

education have caused variations within the social 

and the cultural context. Social norms started to 

change, thus the number of sex partners are 

expected to increase 3 . This change was quite rapid 

and yet uneven through the society. Although still 

mostly traditional, now Turkey represents a 

complex cultural structure with diverse social 

norms. In some parts of the community discussing 

sexuality is a taboo while in others it is discussed 

indirectly or sometimes openly. The approach to 

sexuality influences the knowledge concerning 

HIV/AIDS. In a study conducted among high 

school students in Turkey, one of the most 

important factors influencing the level of 

knowledge was the attitude of the family about 

sexuality. The students who discussed sexuality 

comfortably within the family had the highest 

knowledge scores. The scores were less among 

the ones who discussed sexuality indirectly and 

the least who among the ones whose families 

considered sexuality as a taboo 15 . 

A qualitative study, which was published in 1995, 

evaluated the beliefs and attitudes of Turkish 

women and men 4 . This study points out that 

women consider “cleanness” as the important 

factor in HIV prevention. The main belief is that 

by keeping clean i.e. vaginal douche women can 

prevent HIV infections. This belief is not 

unexpected since the association of personal 

hygiene was promoted for the prevention of many 

infectious diseases during the previous years. 

Differently from women, men considered 

themselves as “strong” and thus having a 

“biological resistance” for the disease. These two 

important concepts and the belief models should 

be further evaluated in order to plan effective 

intervention strategies, which aim behavior 

change. 

Although it is the second most common route of 

transmission, the presence of MSM has been 

denied. The stigmatization and discrimination 

prevent these men to accept their behavior leading 

93




to the internalization of homophobia. These 

people show high-risk behavior and can not 

access the already limited preventive services. 

Due to social pressure most MSM also have 

heterosexual relations and so do not consider 

themselves as homosexual 16 . 

• Attitudes of health care workers 

Since HIV/AIDS is integrated into the medical 

curriculum recently and the prevalence is 

relatively low, many health practitioners lack 

experience on diagnosis, treatment and 

counselling skills 8 . So among the health care 

workers, the bulk of the knowledge about 

HIV/AIDS is gained from the media just like the 

other members of the society, which resulted in 

the formation of stigmatization and discrimination 

towards PLHA. A research carried out among 

surgeons in one of the leading teaching hospitals 

in the capital of Turkey revealed that doctors 

overestimated the risk for acquiring the HIV. 

Moreover they had negative attitudes as anger and 

worry towards PLHA. Doctors were less willing 

to interact with AIDS patients and they did not 

want to work with professionals who had AIDS in 

the same environment 17 . 

• Demographic structure 

15-24 year old persons account for nearly the half 

of all new HIV cases worldwide 18 . Turkey has a 

young population and nearly 27% of the 

population is between the ages of 15-29 11 . In a 

study carried out in a university in Turkey, it was 

determined that more than one third of the 

students had had sexual experience, most of them 

at the ages of 15-19 19 . Research evaluating the 

knowledge of young people about HIV/AIDS 

indicated that their knowledge concerning STIs 

was inadequate 15,19,20 . The study carried out by 

Ungan determined that there was also relatively 

low level of condom use among both genders 20 . 

•Male circumcision: 

Today the role of male circumcision, which is a 

very frequent practice among the Turkish 

population, is being discussed for the prevention 

of HIV/AIDS in the medical literature. Although 

male circumcision does not prevent HIV 

transmission entirely, some studies indicate that it 

reduces the risk. Yet these observational studies 

are criticized since their results could be 

confounded by behavioral practices 21 . However, 

recently an observational study took into account 

ethnic, religious differences and controlled for the 

sexual behavior of men. This study determined 

that uncircumcised men had more than a two fold 

increased risk per sex act compared to 

circumcised men 22 . In Turkey, the risk of 

transmission could be less than the expected since 

the main mode of transmission is the heterosexual 

relationship and most men are circumcised before 

they become sexually active in Turkey. 

Traditional family life, the migration of workers 

together with their families and the prohibition of 

sexual relationships before marriage in the rural 

areas might also serve as preventive factors. 

Current prevention and control activities 

In Turkey, although there were important steps 

taken in the first years of the epidemic by the 

Ministry of Health, national policy was not in 

action as recommended by the UN’s Declaration 

of Commitment. In 1985, when the first case was 

notified HIV/AIDS was included in the list of 

infectious diseases that should be notified. In 

1987, compulsory serologic test was applied for 

some of the vulnerable groups. But since the 

reported number of cases was relatively small, 

HIV/AIDS was not considered as one of the 

priorities of the country. On the other hand, 

despite the efforts of NGOs, the business 

community was not involved and did not provide 

the support, which it did for other health projects, 

due to the stigma attached to HIV/AIDS. 

In 1996 National AIDS Commission was 

established which was the principal decision 

authority at the national level. National AIDS 

Commission consists of representatives from 

different ministries, NGOs and occupational 

organizations, which work related to HIV/AIDS. 

The main aim of the Commission was to develop 

and recommend strategies for the prevention of 

HIV/AIDS by intersectoral collaboration. But the 

Commission was not able to function as required 

due to the rapid turnover of the ministers 23 . In 

2002 national objectives and strategies were 

formulated and an Action Plan was developed. 

But since it lacked the leadership and the financial 

support, the plan was not implemented 24 . 

In Turkey, the funds released from the 

international NGOs, particularly from the United 

Nations System, was inadequate to carry out the 

required activities. Recently, United Nations 

Global Fund provided funds in order to support 

the National Action Plan 25 . Lately 55 million 

EURO was donated by the European Union for 

the Reproductive Health Program to Turkey. 

Hence with this fund, the aim of improving the 

sexual and reproductive health status of the 

Turkish population especially women and youth 

94




will be achievable through the projects 

implemented by NGOs in collaboration with the 

Ministry of Health 9 

Also, the Ministry of Health adopts a strategy, 

which aims to combine the reproductive health 

services to the routine services in order to 

encompass the persons who do not have 

accessibility to the services and who do not get 

comprehensive care. Until 2015 this strategy will 

be implemented in all health care institutions and 

predominantly in primary health care centers. One 

of the main subjects of this program is to increase 

the demand and supply of services 26 . 

NGOs 

After attending the International Population and 

Development Conference in 1994 in Cairo, both 

the Ministry of Health and the NGOs changed 

their services taking into consideration a 

comprehensive reproductive health approach. 

New NGOs focusing on STIs and HIV/AIDS 

were founded. Through the last 20-30 years, 

NGOs implemented programs and adopted 

strategies focusing on new service models, 

training and communication, needs assessment, 

services to disadvantaged groups, which increased 

the demand and the accessibility for the services 27 . 

There are various NGOs which function in the 

field of HIV/AIDS in Turkey. Differently from 

the official organizations, the decision making 

process is faster and not as bureaucratic. Since 

NGOs function more flexible and rapid, and are 

aware of the needs of the community they operate 

as an efficient resources 27 NGOs both participate 

in the prevention-control activities and also 

together with the international organizations in 

motivating the government to take action 8 . Their 

activities mostly focus on training, 

communication, advocacy, some of which target 

groups under high risk as sex workers, IDUs, 

MSM and the street children 8 . 

Care and treatment of the people living with 

HIV/AIDS 

WHO estimates the percentage of adults covered 

among those in need of antiretroviral treatment as 

60% for Turkey 28 . In Turkey nearly 65% of the 

population is covered with health insurance 29 . 

Although there are some problems in the 

implementation, HIV/AIDS treatment expenses 

are covered by these insurance systems. In 1994 a 

new procedure was utilized for persons most 

deprived and not covered by the insurance. 

Persons who do not have any insurance and are 

below a certain economic level could get “green 

card” which enables them to get the services and 

treatment free of charge. 

Recently, it was demonstrated that treatment 

programs that are not combined with effective 

prevention activities will have only a small impact 

on the incidence of HIV over the next 15 years. 

The research underlines that only if effective 

prevention is practices treatment will be 

affordable in the long run. This result focuses on 

the need of an integrated approach consisting of 

prevention and tratment as the most cost effective 

way 30 . 

Future challenges 

•Economic development, larger investment in 

health and education sectors, maintaining equity is 

important not just for the prevention and control 

of HIV/AIDS, but for the well being of our 

society. 

•Political commitment by the Turkish 

Government is a prerequisite for developing and 

maintaining effective prevention-control activities 

as well as raising and allocating funds to this 

issue. Political determination will improve the 

decision making process, the implementation, 

monitoring and evaluation of activities carried out 

by the National AIDS Commission. Also political 

support will accelerate the activities of various 

NGOs that have been working in this area with 

limited resources. 

•A comprehensive and a reliable surveillance 

system which also includes the indicators 

concerning high-risk behavior should be adopted 

for STIs and HIV/AIDS 3 . 

•Adopting and evaluating programs that target 

behavior change are necessary for young people 

and the vulnerable populations. The believes, 

values, attitudes ,behaviors and risk perceptions of 

the Turkish society regarding STIs and HIV/AIDS 

should be studied and better understood in order 

to develop effective prevention programs. Gender 

power inequalities, the low rate of condom use 

should be dealt with. 

•Sexual health education including STIs and 

HIV/AIDS should be covered within the 

curriculum and awareness should be raised during 

the early school years. The trainers providing 

sexual health education should be trained and 

empowered 31 . 

•Counseling and voluntary testing (VCT) services 

for STI and HIV/AIDS should be provided 

widely, particularly to the vulnerable groups. Each 

health care organization should by law encompass 

95




a trained health care worker for the counseling 

services. 

•In order to maintain prevention, early diagnosis 

and treatment of STI, the services should be 

integrated to the primary care level. The personnel 

working in the primary care should be adequate 

and qualified to provide these services effectively. 

•NGOs can strengthen their capacity by providing 

technical assistance and financial support from 

United Nations, European Union or other 

international organizations. It is important to use 

the scarce sources in a most effective way without 

duplicating the activities. The National AIDS 

commission should provide the synergistic 

function of NGOs and maintain intersectoral 

cooperation. 

CONCLUSION 

The present studies, although small-scaled, 

indicate that high risk behavior particularly not 

using condoms in commercial sex is prevalent 32-34 . 

The low number of cases can be explained by the 

inadequacy of VCT services and so the low 

number of cases getting HIV tests. Yet, the highly 

accelerating epidemic in the former Eastern Block 

countries and the high mobility in the region 

suggest a potential HIV/AIDS epidemic. Although 

there are important deficiencies in the prevention 

program, important steps are taken in order to put 

into action some of the above-mentioned 

recommendations. Hopefuly, the Turkish 

Reproductive Health Program and the HIV/AIDS 

Prevention and Support Project will be important 

in achieving the goals by both the Ministry of 

Health and the NGOs working in this field. 

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REVIEW 

MANYETİK REZONANS GÖRÜNTÜLEME VE ANESTEZİ 

Berrin Işık 

Gazi Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Ankara, Türkiye 

ÖZET 

Manyetik rezonans görüntüleme (MRG) ünitesi anestezist için ortamdan, hastadan, işlemden kaynaklanan 

farklı özellikleri taşıyan ve giderek daha fazla talebin olduğu bir uygulama sahasıdır. Manyetik rezonans 

görüntüleme ünitesinin ve burada anestezi uygulanan hasta grubunun özelliklerinin bilinmesi hasta ve 

çalışanların güvenliği yanında verimliliği de artıracaktır. Bu yazıda MRG ünitesinde sürdürülen anestezi 

uygulamalarının derlenerek bildirilmesi hedeflenmiştir. 

Anahtar Kelimeler: Manyetik Rezonans, Görüntüleme, Anestezi 

MAGNETIC RESONANCE IMAGING AND ANESTHESIA 

ABSTRACT 

The magnetic resonance imaging (MRI) unit is a challenging environment for the anesthesiologist, and 

carries inherent risks. Several factors account for this, including the remote location, the unique features of 

the magnetic resonance imaging scanner, and patient-related factors. Understanding the implications of the 

magnetic resonance imaging environment will facilitate ensuring the safety of the patient and personnel. In 

this rewiev we aim to give information about anesthetic applications in the MRI unit as compiled. 

Keywords: Magnetic Resonance, Imaging, Anesthesia 

GİRİŞ 

Yüksek görüntü kalitesi ve bilinen bir zararının 

olmaması nedeniyle günümüzde manyetik 

rezonans görüntüleme (MRG)'ye olan talep 

giderek artmaktadır. Ancak şiddetli gürültü 

varlığı, görüntü sağlanabilmesi için bu işlem 

sırasında tam hareketsizliğin gerekmesi ve dar 

tubuler bir alana girme zorunluluğu özellikle 8 yaş 

altı çocuklarda ve hareketsiz kalamayan, zihinsel 

özürlü ya da kapalı alan korkusu olan erişkinlerde 

sedasyon veya genel anestezi uygulamasını 

gerekli kılmaktadır 1-6 . Takip ve tedavisi gereken 

kritik hastalarda ise monitorize hasta bakımı için 

anestezistin bulunması zorunlu olmaktadır. 

Görüntülemenin kuvvetli manyetik alanda 

yapılması özel donanımı ve yine hasta grubunun 

özellikleri dikkatli bir değerlendirme, hazırlık ve 

deneyimi gerektirmektedir 5,6 . 

Bu yazıda MRG sırasında anestezi 

uygulamalarında dikkat edilmesi gereken konular 


Berrin Işık 

e-mail: berrinisik@gazi.edu.tr 

Gazi Üniversitesi Týp Fakültesi, Anesteziyoloji ve Reanimasyon 

Anabilim Dalý, Ankara, Türkiye 

ile literatür bilgileri ışığında alternatif anestezi 

uygulamalarının bildirilmesi hedeflenmiştir. 

MANYETİK 

GÖRÜNTÜLEME NEDİR? 

REZONANS 

Manyetik rezonans görüntüleme; statik ve 

gradient manyetik sahada dokuya gönderilen 

radyo dalgalarının uyardığı hücrelerdeki hidrojen 

atomlarının ürettiği enerjinin, özel ara birimler 

(koil) sayesinde bilgisayar ortamına aktarılarak 

görüntüye dönüştürüldüğü, noninvaziv bir 

görüntüleme yöntemidir. Alınan sinyallerin 

yoğunluğunun doku tipine göre değişmesi ise 

görüntülemenin esasını oluşturmaktadır. Manyetik 

rezonans görüntüleme sırasında en sık hidrojen 

kullanılmasının nedeni, tek proton içermesi ve 

insan dokularında en fazla bulunan elementlerden 

olmasıdır. Radyo dalgaları varlığında hidrojen 

atomları manyetizmanın etkisiyle düzgün şekilde 

sıralanırlar. Bu dizilim sırasında elde edilen 

yoğunluğa göre bilgisayar ortamında görüntü 


98


Berrin Işık 

Manyetik rezonans görüntüleme ve anestezi 

oluşturulur. Diğer radyolojik görüntüleme 

yöntemleri ile karşılaştırıldığında iyonizan 

radyasyon içermemesi en önemli avantajıdır 6,7 . İki 

- dört Tesla (T) gücündeki manyetik sahanın insan 

hücreleri üzerine zararlı etkisi gözlenmemiş, 

Amerikan Food and Drug Administration (FDA) 

derneği risk açısından MRG cihazlarını sınıf II 

olarak tanımlamıştır 8 . MRG sırasında yaşanan 

komplikasyonlar genellikle ferromanyetik 

objelerle ilgilidir 7-11 . 

MANYETİK 

REZONANS 

GÖRÜNTÜLEME 

VE 

FERROMANYETİK CİSİMLER 

Manyetik sahanın gücü genellikle 0.15 ile 2 T 

arasında (1 T = 10,000 gauss) olup, bu değer yerin 

normal manyetik çekim gücü olan 0.5 gauss ile 

karşılaştırıldığında çok yüksektir. Görüntüleme 

için zorunlu olan bu kuvvetli manyetik alan 

ferromanyetik cisimlerin kuvvetle çekilmesine 

neden olur. Metal oksijen tüpleri, cerrahi 

pansuman aletleri manyetik alanda hızla hareket 

ederek zarar verebilir 9-11 . Klemp, pens, makas, 

steteskop, non-lityum piller, standart medikal gaz 

silindirleri ferromanyetik cisimlerdir. Çelik 

(stainless steel), nikel, titanyum ve plastik ise 

manyetik rezonans (MR) uyumlu materyallerdir. 

Hasta ya da çalışanların vücudunda ferromanyetik 

cisimlerin varlığı dikkat edilmediğinde bir 

faciayla sonuçlanabilir. Bu nedenle pace-maker, 

prostetik kalp kapakçıkları, kemik implantları, 

retina ya da beyin damarlarında bulunan metalik 

klipsler, implante infüzyon pompaları, koklear 

implant, saçma parçacıkları olup olmadığı 

dikkatle sorgulanmalıdır. Manyetik alan pacemaker 

ile ilgili olarak elektromanyetik etkileşim, 

programda bozulma, silinme, asenkron moda 

geçiş, kapanma ve ısınmaya bağlı sorunlara neden 

olarak yaşamı tehdit eder 4,7-11 . 

Son yıllarda kullanılan implante materyallerin 

çoğu MR uyumlu olduğundan özellikle eski tarihli 

implantlarda dikkatli olunmalı, yerleştirilmiş olan 

metalik implantların MR uyumlu olup olmadığı 

değerlendirilmeli, güncellenerek yayınlanan MR 

uyumlu implantların listesi MRG ünitelerinde 

bulundurulmalıdır 7,8 . 

Dövme ve kalıcı makyajda ferromanyetik 

maddeler kullanıldığından MRG sırasında lokal 

cilt hasarı yaratabilmektedir 12 - 14 . 

Floopy disketler, USP, telefon kartları, manyetik 

yaka kartları, bankamatik kartları, saat pilleri de 

kuvvetli manyetik alan etkisi ile bozularak 

işlemez hale geleceğinden ortamda 

bulundurulmamalıdır. 

Manyetik rezonans görüntüleme sırasında hasta 

izleminde ve anestezi uygulamasında kullanılacak 

olan monitör ve cihazlar da ferromanyetik parça 

içermeyen, MR uyumlu cihazlar olmalıdır. 

MONİTÖR VE DİĞER ARAÇ 

GEREÇLER 

Hasta güvenliği için MRG ünitesinde de 

Amerikan Anesteziyologlar Derneği (ASA) 

Operasyon Odası Dışı Anestezi Uygulamaları 

Standardında 15 belirtilen donanım desteği ve 

anestezi uygulaması yapabilmek için gerekli olan 

16,17 

asgari monitorizasyon şartları 

oluşturulmalıdır. Manyetik rezonans uyumlu 

monitörlerde bile görüntüleme sırasında EKG'nin 

sağlıklı değerlendirilemeyebileceği 18 ve iskemik 

kalp hastalığı olan hastalarda takip güçlüğü 

yaşanabileceği bilinmelidir. 

Manyetik alanda standart EKG monitörü 

kullanılması elektrot telleri anten görevi yaparak 

görüntüyü bozacağından ya da teller ısınarak 

hastanın yanmasına neden olabileceğinden uygun 

olmayıp, ısınmayan karbon yapıda elektrod 

kabloları olan MR uyumlu monitörler 

kullanılmalıdır. Periferik oksijen satürasyonunu 

ölçmede ferromanyetik olmayan, fiberoptik 

kablolu sensor tercih edilmelidir. Ancak bu da 

yanıkları önleyemeyebilir. Noninvaziv kan basıncı 

ölçümünde ise en uygunu osilometrik metoddur. 

Solunum fonksiyonunu değerlendirmede periferik 

oksijen satürasyonu yanı sıra, soluk sonu 

karbondioksit basıncı (EtCO 2 ) ölçümünün 

yapılması güvenli olacaktır 4 . Yeni MR uyumlu 

fizyolojik monitorizasyon sistemleri; invaziv kan 

basıncı, santral venöz basınç ölçümleri yanında 

fiberoptik yüzey sensörleri aracılığı ile ısı 

monitorizasyonu da yapabilmektedir. 

Manyetik rezonans görüntüleme ünitesinde 

anestezi cihazı MR uyumlu olmalıdır. Bu amaçla 

üretilmiş MR uyumlu anestezi cihazları oldukça 

pahalı olmakla birlikte medikal marketlerde 

bulunmaktadır. 

Ferromanyetik medikal gaz silindirleri manyetik 

ortamda hızla hareket ederek hasta ve cihazlara 

zarar verebileceğinden gaz silindirleri 

alüminyumdan yapılmış olmalıdır 4,7,9,11 . 

MANYETİK 

REZONANS 

GÖRÜNTÜLEME SIRASINDA HASTA 

BAKIMI VE KONFORU 

Manyetik rezonans görüntüleme sırasında 

anestezistin hastadan uzakta olması ve hastayı 

yakından izleyememesi en önemli sorundur. Bazı 

servislerde kapalı sistem video ile hasta 

99


Berrin Işık 


görüntüleri izlenmekte ise de, sıklıkla 

monitorizasyon ile elde edilen vital parametrelerin 

değerlendirilmesi ile hasta takibi yapılmaktadır. 

Manyetik rezonans uyumlu anestezi cihazının ve 

monitörlerinin olmadığı merkezlerde ise anestezist 

MRG odasında bulunarak hastayı izlemekte, fakat 

şiddetli gürültü nedeni ile özellikle uzun süreli 

işlemlerde çalışanlar açısından sakıncalar 

yaratmakta ve hastanın vital parametreleri de 

sağlıklı olarak takip edilememektedir. 

Kapalı alan fobisi olan erişkinlerde herhangi bir 

sedasyon veya anestezi uygulanmadığında, 

şiddetli kaygı nedeniyle hareketsiz kalamadıkları 

için görüntüleme mümkün olamamaktadır. Murpy 

ve Brunberg 19, üniversite hastanesinde rastgele 

seçilen bir 7 haftalık periyotta MRG yapılan 18 

yaş ve üzeri toplam 939 hastanın 134'ünde 

(%14.3) oral sedasyon, İV sedasyon veya genel 

anestezi gerektiğini, sedasyon uygulananların; 

%64.1'inin kadın, %35.8'inin erkek olduğunu, 

%66.4'ünün beyin görüntülemesinin yapıldığını, 

daha önce MRG deneyimi olması ortalamasının 

ise 1.56 olduğunu bildirmişlerdir. 

Manyetik rezonans görüntüleme sırasında gürültü 

de hasta konforunu ve işitme fonksiyonunu 

etkileyen bir faktördür. Radyofrekans dalgaları 

sırasında tellerin vibrasyonu sonucunda 1.5 T 

gücündeki MR'da şiddeti 95 dB'e varan gürültü 

ortaya çıkar. Kulak tıkaçları kullanılması işitme 

hasarını önlemede ya da azaltmada etkili ve pratik 

bir çözümdür 20 . 

Manyetik rezonans ortamında bir diğer risk ise 

yanık tehlikesidir 

4,14,21,22 . Monitorizasyonda 

kullanılan tellerle olan yanıkların yanı sıra hasta 

vücuduna tedavi amaçlı yapıştırılan yama (patch) 

ile de yanıklar bildirilmiştir 23 . 

Hastada göz makyajı veya dövme varlığında 

görüntüleme sırasında lokal cilt irritasyonu 

gözlenebilir 12-14 . Anestezi altındaki bir hastada 

görüntüleme sırasında herhangi bir yakınma 

olmayacağından anestezistin bu konuda gerekli 

uyarıyı işlem öncesi yapması uygun olacaktır. 

Manyetik rezonans görüntüleme sırasında görüntü 

kalitesini artırmak amacıyla kontrast madde 

seçiminde sıklıkla düşük ozmolar iyonik madde 

olan Gadopentetate dimeglumine (Gadolinium) 

tercih edilmektedir. Bunun eliminasyon yarılanma 

ömrü 1.3-1.6 saat olup asıl atılım yolu 

böbreklerdir. Yenidoğan ve küçük çocuklarda 

klirensi erişkine kıyasla daha düşüktür. Bulantı 

kusma, başağrısı, tromboflebit şeklinde yan 

etkileri bildirilmiştir. Yaşamı tehdit eden alerjik 

reaksiyon sıklığı diğer iyodinize ajanlardan azdır 

24-27 . Murphy ve ark 28, kontrast madde olarak 

gadolinyum verilen toplam 21000 hastanın 

kayıtlarını değerlendirdiklerinde 36 hastada 

(15'inde bulantı kusma, 12'sinde yaygın eritem 

veya cilt irritasyonu, 7'sinde solunum yakınmaları, 

2'sinde solunum sıkıntısı ve periorbital ödem 

şeklinde) alerjik reaksiyon görüldüğünü, yalnızca 

5'inde tedavi gerektiğini bildirmiştir. Yüz beş 

merkeze ait bilgilerin değerlendirildiği bir diğer 

çalışmada ise 687,255 gadopentetate dimeglumine 

uygulaması sonrası 314 (% 0.046) olguda nonalerjik 

reaksiyon, 107 (% 0.016) olguda hafif, 28 

(% 0.004) olguda orta ve 5 (% 0.001) olguda ciddi 

alerjik reaksiyon olduğu bildirilmiştir 29 . Alerjik 

reaksiyonlar seyrek görülmekle birlikte fatal 

reaksiyonlar da gelişebildiğinden gerekli ilaç ve 

malzemeler hazır tutulmalıdır 30 . 

MANYETİK 

REZONANS 

GÖRÜNTÜLEME 

SIRASINDA 

ANESTEZİ UYGULAMALARI 

Manyetik rezonans görüntüleme sırasında anestezi 

uygulaması yakın zamana kadar, yalnızca 

hareketsizliğin sağlanması için gerekmekteyken, 

günümüzde; santral sinir sistemine ait girişimler 

sırasında da MRG yapıldığı bildirilmektedir 31,32 . 

Anestezi tekniği ve ajanlarının seçimi hastanın ve 

işlemin özelliklerine göre yapılmalı, 

görüntülemenin süresi, cerrahi girişim yapılıp 

yapılmayacağı da göz önünde bulundurulmalıdır. 

Santral sinir sistemine ait girişimler sırasında 

yapılan MRG için uygulanacak anestezi 

yönteminde; cerrahi ağrı, kan kaybı ve beyinin 

homeostazisini etkileyen diğer faktörleri de göz 

önünde bulundurmak gerekmektedir. Schmitz ve 

ark. 32, intraoperatif MRG'nin uygulandığı beyin 

ameliyatlarında; propofol, remifentanil ve cisatraküryumun 

sürekli infüzyonunu başarı ile 

kullandıklarını bildirmektedirler. 

Yalnızca görüntüleme amacıyla yapılan anestezi 

uygulamalarında; bilinçli sedasyon, derin 

sedasyon, rejyonal anestezi, total intravenöz 

anestezi (TİVA) veya inhalasyon anestezisi 

uygulanabilir. Cerrahisiz MRG yapılan 

erişkinlerin % 14 ila % 20'sinin aşırı kaygı ya da 

klostrofobi nedeniyle anestezi desteğine ihtiyaç 

duyduğu gösterilmiştir. Hastaların çoğunda oral 

ya da IV yolla verilen benzodiyazepinler yeterli 

olmaktadır. Sedasyonun yeterli olmadığı 

olgularda uygun monitorizasyon şartları varlığında 

başta propofol ile TİVA olmak üzere hemen tüm 

anestezi yöntemleri kullanılabilir 4,19,33-34 . 

Sevofluranın O 2 /N 2 O içinde düşük 

konsantrasyonlarda maske ile uygulanması ile 

100


Berrin Işık 


bilinçli sedasyon yapılan olgular da vardır 35 . 

Obez hastalarda sedasyon yöntemleri kullanılırken 

havayolu problemleri ile daha sık 

karşılaşılabileceği akılda tutulmalıdır. 

Çocuk hasta grubunda ise; oral 75-100 mg.kg -1 

kloral hidrat, rektal 20-30 mg.kg -1 metoheksital, 

IV yol bulunamayan hastalarda IM 5 mg.kg -1 

ketamin, oral rektal veya IV 4-5 mg.kg -1 

pentobarbital, IV 2-3 mg.kg -1 yükleme dozundan 

sonra 100 µg.kg -1 .dk -1 propofol infüzyonu, oral 

0.25-0.75 mg -1 .kg -1 ya da IV 0.05-0.15 mg.kg -1 

midazolam önerilebilir. Kloral hidrat metabolitleri 

de aktif olduğundan çocuklarda özellikle 

yenidoğan döneminde derlenmenin çok 

uzayabileceği bilinmelidir. Ketamin, 

sekresyonlarda artışa yol açacağından, 

antisiyalogog bir ajanla birlikte verilebilir. 

Midazolam ile sedasyon yeterli olmadığında 

istemsiz hareketler daha sık görüldüğünden çok 

seçilen bir alternatif değildir. Sedasyon uygulanan 

çocuklarda; adenotonsiler hipertrofi, obsrüktif 

uyku apnesi, üst solunum yoluna ait patoloji 

varlığında solunumun baskılanarak hipoksemiye 

neden olabileceği bilinmelidir 4,36 . 

37, 

Malviya ve ark. çocuklarda MRG veya 

kompütorize tomografi sırasında sedasyon 

uygulandığında hareket nedeniyle 

görüntüleyememe ve hipoksemi riskinin daha 

yüksek olduğunu, görüntülemenin tekrar edilmesi 

ya da işlemin iptal edilmesinin; zaman, para ve 

emek kaybına yol açarak maliyeti önemli ölçüde 

artırdığını, bu nedenle genel anestezinin daha 

başarılı olduğunu bildirmiştir. Sedasyonda 

başarısızlık merkezlere göre değişmekle birlikte 

%5 ile %16 arasında değişen oranlardadır 2,5 . 

Keengwe ve ark. 38, 90 mg.kg -1 (maksimum 2g) 

kloral hidrat ile sedasyon uygulanan 5 yaş altı 727 

hastanın % 6,9'unda sedasyonun başarısız 

olduğunu bildirmiştir. Çocukların uyumsuz kişilik 

özellikleri de sedasyon yetersizliklerinde etkili bir 

faktördür 2 . 

34, 

Usher ve ark. 100 çocuk olguda MRG 

nedeniyle maskeyle oksijen desteği ile spontan 

solunum korunurken, ortalama 3.9 mg.kg -1 

indüksiyonunun ardından 193 µg.kg -1 .dak -1 

infüzyon şeklinde sürdürdükleri propofol 

anestezisi ile havayolu güvenliğinin ve hızlı 

derlenmenin sağlandığını ve güvenle 

kullanılabileceğini bildirmiştir. Bir diğer anestezi 

yöntemi de rektal midazolam ve S(+) ketamin ile 

endotrakeal entübasyon gerektirmeksizin 

sedasyon/genel anestezi sağlanmasıdır 

5 . De 

Sanctis Briggs 39, yaşları 1 gün-12 ay arası değişen 

640 olguda maske ile sevofluran uygulaması ile % 

97,9 olguda optimal başarıyı sağladıklarını 

bildirmektedir. Genel anestezi ve sedasyon 

uygulamalarına bir alternatif olarak Gozal D ve 

Gozal Y 40, ciddi spastik paraparezisi olan 

hastalarda spinal anesteziyi güvenle 

uyguladıklarını bildirmektedir. 

Klinik uygulamalarımızda özellikle çocuk 

grubunda sıklıkla %50/50 O 2 /N 2 O içinde %7-8 

sevofluran ile inhalasyon indüksiyonunun 

ardından laringeal maske yerleştirerek %50/50 

O 2 /N 2 O içinde % 1-1.5 konsantrasyonda 

sevofluran inhalasyonunu başarılı buluyoruz. 

Aşırı korkan çocuklara 0.5 mg.kg -1 (maksimum 15 

mg) oral midazolam, kaygılı erişkin hastalara 

0.02-0.05 mg.kg -1 tek doz IV midazolam 

premedikasyonu, ağrı nedeniyle duramayan 

hastalara 1-2 µg.kg -1 IV fentanil, kapalı alan fobisi 

nedeniyle uyum gösteremeyen erişkinlere de 100- 

200 µg.kg -1 .dk -1 IV propofol ya da 1µg.kg -1 10 

dakika içinde yükleme dozundan sonra 

0.2/0.7µg.kg -1 .saat -1 deksmedetomidin infüzyonu 

ile sedasyonu, inhalasyon anestezisinin 

kontrendike olmadığı kritik hastalarda ise %100 

O 2 ya da %50/50 O 2 /N 2 O içinde düşük 

konsantrasyonda sevofluran ile inhalasyon 

anestezisini tercih ediyoruz. 

Bazı merkezlerde MRG sırasında sedasyon veya 

anestezi uygulamasını eğitimli hemşireler 

yürütmekteyse de anestezist olmayanların 

uygulamalarının anestezistlerin uygulamaları ile 

karşılaştırıldığında hipoksemi ve başarısız işlem 

oranının daha yüksek olduğu bildirilmiştir. Aynı 

şekilde derlenmede uzama, motor dengesizlik, 

ajitasyon, gastrointestinal yan etkiler ve taburcu 

sonrası huzursuzluk da daha fazla 

bildirilmektedir 41-42 . Hastaların özelliklerine 

uygun net protokoller geliştiren anestezistlerin 

görev aldığı kliniklerde başarı oranı çok 

yükselmektedir. 

MANYETİK 

REZONANS 

GÖRÜNTÜLEMEDE 

HASTA 

GRUBUNUN ÖZELLİKLERİ 

Anestezi uygulanması planlanan tüm hastalarda 

olduğu gibi MRG öncesi de hastalar sistemik 

muayene ve uygun tetkikler yapılarak 

değerlendirilmiş olmalıdır. İntrakranyal kitle ön 

tanısıyla MRG istenilen olgularda, kafaiçi 

basıncını artıracak uygulamalardan kaçınılmalıdır. 

Henüz tanı konulmamış araştırma aşamasındaki 

olgularda, özellikle sendrom düşünülen bebek ve 

çocuklarda muayene ile elde edilen klinik veriler 

dikkatle değerlendirilmeli ve olası 

komplikasyonlar için önlemler alınmış olmalıdır 43 . 

Görüntüleme sırasında EKG ile iskemi takibi 

101


Berrin Işık 


yeterince yapılamayacağından myokardiyal 

iskemi riski olan hastalar, kan basıncı labil olan ya 

da inotrop ajan desteği gereken hastalarda 

hemodinamik stabilizasyonu sürdürmek ve 

izlemek zor olacağından, bu hastalarda MRG 

sırasında doğabilecek sorunlar klinisyenlerle 

açıkça konuşularak risk belirlenmeli ve ortak 

karara varılmalıdır. 

ANESTEZİ SONRASI SORUNLAR 

Manyetik rezonans görüntüleme için uygulanan 

anestezi sonrası yan etkilerin değerlendirildiği 

çalışmalarda en sık bulantı/kusma 

bildirilmektedir. Sandner-Kiesling ve ark. 44, 

kraniyal MRG nedeniyle genel anestezi uygulanan 

168 çocuk olguyu 72 saat izleyerek yan etkileri 

değerlendirdikleri çalışmalarında 14 farklı yan 

etki gözlendiğini, yan etkilerin en çok ilk 1 saatte 

görüldüğünü, nörolojik yan etkilerin 5 yaş 

üzerinde ve intrakranyal lezyonu olanlarda daha 

çok görüldüğünü, en sık görülen yan etkilerin; baş 

ağrısı, ajitasyon, güçsüzlük, baş dönmesi ve 

hıçkırık olduğunu bildirmiştir. Malviya ve ark. 42 

ise nöro-görüntüleme için kloral hidrat kullanılan 

çocukların %5'inden fazlasında 6 saatten uzun 

süre huzursuzluk ve ajitasyon görüldüğünü, 

bunların normal aktivitelerine dönmelerinin 

işlemden sonra 2 günü aldığını bildirmektedir. 

45, 

Cravero ve ark. Görüntüleme nedeniyle 

sevofluran anestezisi verilen 18 ay-10 yaş arası 

çocuklarda kontrol grubunda %56 oranında 

derlenme ajitasyonu gözlenirken, 1 µg.kg -1 

fentanil verilenlerde %12'ye düştüğünü ve küçük 

doz fentanilin cerrahisiz postanestezik derlenme 

ajitasyonunu azaltmada etkili olduğunu 

bildirmiştir. Manyetik rezonans görüntüleme 

sırasında sevofluran anestezisi uygulanan çocuklar 

üzerinde gerçekleştirdiğimiz çalışmalarda anestezi 

indüksiyonu ardından verilen 1 µg.kg -1 

deksmedetomidinin ve anestezi indüksiyonunda 

veya sevofluran sonlandırılmadan önce IV yolla 

verilen 1 µg.kg -1 fentanilin derlenme ajitasyonu 

görülme sıklığını azalttığını saptadık 46,47 . Çocuk 

olgulardaki sedasyon uygulamalarında mortalite 

gibi ciddi komplikasyonların oranını tam olarak 

bilmek elde yeterli veri olmadığından mümkün 

değildir. 

Klinik gözlemlerimize göre derlenme döneminde 

en sık; bronkospazm, hipoksi, bradikardi gibi kısa 

sürede düzelen solunum ve dolaşım sistemine ait 

sorunlar ile derlenme ajitasyonu ve bulantı-kusma, 

karın ağrısı gibi gastrointestinal sisteme ait 

yakınmalar izlenmektedir. 

Hangi yöntem kullanılırsa kullanılsın hedef, 

hastanın stabilitesinin sürdürülmesi ve hızla 

derlenmesinin sağlanmasıdır. Uyanmada sorun 

olabileceği öngörülen olguların derlenme 

dönemini, deneyimli ekip ve donanımın 

bulunduğu ameliyathaneye ait postanestezik 

derlenme ünitesinde geçirmesi uygun olacaktır. 

Bu amaçla monitorizasyon ve oksijen desteğinin 

sürdürülebileceği transport imkânları 

hazırlanmalıdır. Transport sırasında anestezi 

sürdürülebileceği gibi uyandırmayı takiben hızla 

nakil de düşünülebilir. 

Sonuç olarak; MRG nedeniyle anestezi 

uygulamasına giderek daha fazla talep olmaktadır. 

Bu ortamın, donanımın ve anestezi 

uygulamalarının özelliklerinin iyi bilinmesi hasta 

konforunu ve iş başarısını artırırken çalışanın da 

güvenliğini artıracaktır. 

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