Marmara Medical Journal Marmara Üniversitesi Tıp Fakültesi Dergisi

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 Medical Journal 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 Medical Journal 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 www.marmaramedicaljournal.org

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. www.marmaramedicaljournal.org

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 www.marmaramedicaljournal.org

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ORIGINAL RESEARCH ATTITUDES AND PRIORITIES OF TRAINING CLINICIANS IN DIAGNOSING DELIRIUM IN AN ACADEMIC HOSPITAL M.Kemal Kuşcu, Volkan Topçuoğlu, Aylan Gımzal Gönentür, Yasin Bez, Çağrı Yazgan, Nurhan Fıstıkçı, Duygu Şahin Biçer, Ali Keyvan Department of Psychiatry, School of Medicine, Marmara University, Istanbul, Turkey ABSTRACT Objective: The aim of our study is to explore the attitudes and practices of residents on establishing a diagnosis of delirium and their clinical intervention in different clinical settings in Marmara University Hospital. Methods: Seventy-five residents in different clinical settings in Marmara University Hospital completed a 14-item questionnaire which focused on their priorities and attitudes concerning diagnosis and treatment of delirium. Results: Orientation difficulties, clouding of consciousness and hallucinations were chosen as the most frequently encountered symptoms of delirium. For the purpose of establishing the etiology of delirium the most frequently preferred method was biochemical screening. Metabolic imbalances were most frequently found while only less than 50% of participants could establish the etiology. Most of the participants indicated treatment of the specific etiology as the preferred treatment method of delirium. Haloperidol was the most frequently selected medication for symptom control. Discussion: Delirium still remains an important clinical emergency in clinical practice. We hope this study will promote further insight for daily clinical routines in Marmara University Hospital. We believe this effort will provide ground for developing new consensus guidelines for the management of delirium, which will improve the outcome and treatment process of this clinical condition. Keywords: Delirium, Clinical practice BİR EĞİTİM HASTANESİNDE ASİSTAN HEKİMLERİN DELİRYUM TANISINA YÖNELİK TUTUM VE ÖNCELİKLERİ ÖZET Amaç: Çalışmanın amacı klinik eğitimleri sırasında hekimlerin delirium tanısını oluştururken tutumlarının ve buna eşlik eden müdahalelerdeki önceliklerinin saptanmasıdır. Yöntem: Marmara Üniversitesi Tıp Fakültesi Hastanesi nin farklı kliniklerinde eğitimlerine devam eden yetmişbeş asistan hekim delirium tanısına yönelik tutum ve tedavi önceliklerini sorgulayan 14 sorudan oluşan bir değerlendirmeyi tamamladılar. Sonuçlar: Yönelim güçlükleri, bilinç bulanıklığı ve halüsinasyonlar en sık gözlenen delirium semptomları olarak saptandı. Deliryum tanısına yönelik en sık başvurulan metodun biyokimyasal değerlendirme olduğu belirlendi. Genelde % 50 oranında etiyolojik faktörlerin saptanabildiği gözlemlenirken, en sık etiyolojik faktor olarak metabolik nedenler bildirildi. Katılımcıların çoğunluğu etiyolojiye yönelik tedaviyi tercih ederken (% 94.7), en sık kullanılan medikasyonun haloperidol olduğu saptandı. Tartışma: Deliryum gündelik klinik pratiğin içerisinde önemli bir acil durumdur. Çalışmamızın Marmara Üniversitesi Tıp Fakültesi Hastanesi genelinde delirium takip ve tanısında uygun klinik yaklaşım rehberlerinin oluşturulmasına ve sık gözlenen bu klinik durumun tedavi ve prognozuna katkıda bulunacağını umuyoruz. Anahtar Kelimeler: Deliryum, Klinik pratik INTRODUCTION Delirium is an important clinical condition where disturbance in consciousness and cognition represent the common symptomatology based on different etiologies. The essential feature of delirium is a disturbance of consciousness, ranging from attention disturbances to total Corresponding author: M.kemal Kuşcu, MD, Marmara University School of Medicine Department of Psychiatry Tophanelioglu Cad. No: 13-15 34034 Uskudar-Istanbul E-mail: mkkuscu@marmara.edu.tr inability to respond to environmental stimuli accompanied by a change in basic cognitive skills such as memory and language that cannot be better accounted for by a preexisting or evolving dementia. This clinical condition develops over a short period of time, usually from hours to days, and tends to fluctuate during the course of the day 1. The fluctuating course causes an important Marmara Medical Journal 2004;17(3);99-104 99

Marmara Medical Journal 2004;17(3);99-104 M.Kemal Kuşcu, et al. Attitudes and Priorities of Training Clinicians in Diagnosing Delirium in An Academic Hospital burden in making a concrete diagnosis on daily basis. If the underlying etiological factors are found and corrected, recovery is more likely to be accomplished. Delirium occurs in 15-18% of patients on surgical and medical wards, based mostly on referral numbers 2. Its prevalence is higher in specific conditions: 30% in post-coronary artery by-pass graft (CABG) surgery 3 and 50% in post-hip surgery patients 4. A wide variety of physiological and central nervous system (CNS) insults produce delirium, which need extensive differential diagnose. During the last years, systematic research into the prevalence, incidence, and risk factors for delirium has provided valuable insight into this disorder 5. The incidence of delirium depends on the different individual factors and specific etiologies involved. Patients who are at increased risk for developing delirium include the elderly, patients with CNS disorders, postsurgical patients, burn-patients, drug dependent patients, and cancer patients 2. Delirium is one of the leading clinical conditions which can cause an important burden in daily clinical routine 6. Delirium, a medical disorder that results in the morbidity and mortality of patients, is often misdiagnosed and inappropriately treated. Besides being a clinical emergency, delirium has a high mortality rate 7. Delirium remains a poorly managed clinical condition and specific guidelines fail to improve the process and outcome of care 8. Early recognition of delirium might improve the quality of life and general outcome of the medical condition 9. One way of creating these guidelines is to understand the nature of daily routines/ practices in clinical settings. These routines / practices depend heavily on the priorities and attitudes of the medical staff. Clinical decisions are the cornerstones of daily clinical routines in inpatient units. Despite the available clinical algorithms, most of the daily clinical decisions depend on the attitudes and priorities of the clinical staff 10. Despite the importance of the issue, the information on how clinicians assess a delirious patient is still limited. Also, the medical staff dominating the daily clinical routines have an important impact on clinical decisions. Furthermore, there is little information on how the medical staff construct these daily priorities and translate their medical knowledge to practice. How they organize their clinical decisions in daily routine still remains a research area 11. The aim of our study is to explore the attitudes and practices of residents on establishing a diagnosis of delirium and their clinical intervention in different clinical settings in Marmara University Hospital. Sequences of clinical decision and priorities in examining and treating delirium are analyzed in order to understand the clinical and personal needs in managing such a clinical condition in an inpatient setting. METHODS Participants and procedure Seventy-five residents from the internal and surgical wards in Marmara University Hospital participated in the study. Each clinician in surgical and internal medicine wards was visited in and a questionnaire about their daily practices concerning delirium was applied. The respondents participated in the study on voluntary basis. The questionnaire was administered in an interview format. The semi-structured interview consisted of 14 questions focusing on 4 main areas in delirium diagnosis and treatment: (a) Priorities in diagnosing delirium: The participants gave a detailed account of their chosen prognostic symptoms and the course of the delirium, (b) pathway to establish clinical decision: Steps, paths for informations are shared and laboratory procedures are assessed, (c) possible clinical etiologies in delirium, (d) treatment priorities and clinical interventions. RESULTS All the participants were residents working in the Marmara University Hospital. Twenty two (29.3%) of them were male, and 53 (70.6%) of them were female. Fifty-one participants (68%) had been practicing as clinicians for 1-5 years, 21 participants (28%) had been practicing for 6-10 years, and 3 participants (4%) had been practicing for 11-15 years. Forty participants (53.3%) had been in residency for 1-2 years, 20 participants (26.7%) had been in residency for 3-4 years and 15 participants (20%) had been in residency for 5 years and longer. 100

Marmara Medical Journal 2004;17(3);99-104 M.Kemal Kuşcu, et al. Attitudes and Priorities of Training Clinicians in Diagnosing Delirium in An Academic Hospital When the participants were asked about the main symptoms of delirium, they responded as follows: orientation difficulties (74 %), clouding of consciousness (57.3 %), hallucinations (57.3 %), anxiety (45.3 %), psychomotor activation (37.3 %), insomnia (30.7 %), memory deficit (28 %), attention deficit (21.3 %), somnolence (18.7 %), ideas of persecution (16 %), speech problems (12 %), psychomotor retardation (8 %) and depression (2.7 %) consequently. According to the responses of the participants the most prominent symptoms of delirium were anxiety, orientation difficulties and clouding of consciousness, and these were stated significantly higher than the other symptoms of delirium [χ 2 (8, N=72)=60.75, p=0.000]. The follow-up analysis revealed that frequency of the statement of these symptoms by the participants did not differ from each other [χ 2 (2,N=52)=4.3, p=0.13]. Participants were asked to rate the number of delirium cases they had encountered in one year in a multiple choice format (a-0-10,b-11-20,c-21-30,d-31-40,e-41 and more). Most of the participants (N=61) indicated encountering less than 10 delirium cases. Seven participants encountered 11-20, 2 participants encountered 21-30, 3 participants encountered 41 and more cases and there were no participants who encountered 31-40 cases. The analysis revealed that there were significant differences between the groups [χ 2 (3,N=73)=134.28, p=0.000]. In order to carry out follow-up analysis these categories were regrouped as a = 0-10, and b = 11 and more. According to this regrouping, there were 61 participants indicating that they had encountered 0-10 cases, 12 participants indicating 11 and more cases. The results revealed that the number of clinicians who had encountered 0-10 delirium cases (N=61) was significantly greater than the number of clinicians who had encountered 11 and more cases (N=12) [χ 2 (1, N=73) = 32.89, p=0.000]. When the participants were asked about the person who recognized delirium in clinical settings, 76.3% stated residents, 68 % family members, 57.3% nurses, 16% interns and 16% specialists. The result of the McNemar test revealed that a significantly greater number of participants stated nurses as the person who recognized delirium without stating specialists (N=38) than the participants who stated specialists without stating the nurses (N=7) (p=0.000). Similarly, the difference between the number of participants who stated residents as the person who recognized delirium without stating the specialists (N=45) and the number of residents who stated specialists without stating the residents (N=0) was statistically significant (p=0.000). Participants were asked to select one or more of the laboratory methods and clinical interventions which they used to diagnose delirium. Results are shown in table I. The participants were also asked to indicate their preferred method in an open ended format. There was a significant difference between the frequency of application of these methods as their preferred diagnostic method [χ 2 (8,N=70)=273.8, p=0.000]. While 51 clinicians indicated biochemical screening, chest X ray, urinalysis, electroencephalogram, ultrasonography of the abdomen were not indicated by any of the participants. Because these numbers were too small with which to carry out a meaningful analysis, the number of clinicians indicating methods other than biochemical screening were summed up (N=19). The difference between indicating biochemical screening (N=51) and indicating all other methods (N=19) were found to be significant, showing that biochemical screening was the most frequently preferred diagnostic method [χ 2 (1,N=70)=14.62, p=0.000]. Table I: Laboratory methods and clinical interventions used by the residents to diagnose delirium Biochemical screening 90.7% Psychiatric consultation 69.3% Arterial blood gases screening 54.7% Neurological consultation 41.3% CT scan 14.7% Urinalysis 13.3% Chest X ray 12% 101

Marmara Medical Journal 2004;17(3);99-104 M.Kemal Kuşcu, et al. Attitudes and Priorities of Training Clinicians in Diagnosing Delirium in An Academic Hospital Biochemical screening 90.7% Medication 12% Cranial MRI 9.3% Electrocardiogram 8% Electroencephalogram 6.7% Participants were asked to indicate the percentage of cases in which they were able to find an etiology in a multiple choice format (a. 0-25%, b. 26-50%, c. 51-75%, d. 76-100%). A one-sample chi-square test was conducted to assess the differences between these choices. The result was significant [χ 2 (3, N=70)=14.34, p=0.002]. Follow up analyses were conducted. The proportion of participants who found etiology in 0-25% of cases (N=23) was not significantly different than the proportion of participants who found etiology in 26-50% of the cases (N = 27), and the proportion of participants who found etiology in 51-75% of the cases (N = 13) [in order χ 2 (1, N=50) =.32, p =.572; χ 2 (1, N=36) = 2,78, p =.096]. However, the proportion of participants who found etiology in 26-50% of cases (N=27) was significantly greater than both the proportion of participants who found etiology in 51-75% of cases (N=13), and the proportion of participants who found etiology in 76-100% of cases (N=7) [in order χ 2 (1, N=40) = 4,9, p =.027; χ 2 (1, N=34) = 11,77, p =.001}. Finally, the proportion of participants who found etiology in 0-25% of cases (N=23) was significantly greater than the proportion of participants who found etiology in 76-100% of cases (N=7) [χ 2 (1, N=30) = 8,53, p =.003]. Overall, the analysis revealed that most of the participants found etiology in less than 50% of the cases. Etiologies of delirium as indicated by the participants are shown in table II. The participants were also asked to indicate the etiology which they most frequently found, in an open-ended format. There was a significant difference between the frequency of indicating these methods [χ 2 (10, N=73) = 229.73, p=0.000]. While 43 clinicians indicated metabolic imbalances, 10 participants indicated long-term stay in intensive care unit as the most frequently found etiology. All other etiologies were indicated by 5 or less participants each. A one-sample chi square analysis was conducted to compare the proportion of participants who indicated metabolic imbalances with those who indicated long-term stay in an intensive care unit. The result was significant, showing that the most frequently found etiology by the participants was metabolic imbalance [χ 2 (1,N=53)=20.55 p=0.000]. Table II: Etiologies of delirium as indicated by the residents Metabolic imbalances 86.7% Delirium tremens 40% Long period of hospitalization 32% Long-term stay in an intensive care unit 30.7% Respiratory pathologies 26.7% Infections 24% Intracranial pathologies 24% The participants were also asked to indicate the treatment which they most frequently preferred in an open ended format. Treatment of the specific etiology (94.7%), pharmacotherapy (90.7%), observation of the patients (54.7%) and psychotherapy/psychosocial interventions (20%) were stated as options for treatment in delirium patients. There was a significant difference between the frequency of indicating these methods [χ 2 (3,N=71)=108.1, p=0.000]. Fifty-five of the clinicians indicated treatment of the specific etiology as the most frequently preferred treatment option. Because the numbers were too small to carry out a meaningful analysis the number of clinicians indicating treatment options other than treatment of the etiology were summed up (N=16). The difference between indicating treatment of the etiology (N=55) and indicating all 102

Marmara Medical Journal 2004;17(3);99-104 M.Kemal Kuşcu, et al. Attitudes and Priorities of Training Clinicians in Diagnosing Delirium in An Academic Hospital the other treatment options (N=16) were found significant [χ 2 (1,N=71)=21.42, p=0.000]. Medication alternatives used by the participants for the control of delirium symptoms are shown in table III. When they were asked to indicate their first medication choice in an open ended format, alprazolam, haloperidol, risperidone, quetiapine and diazepam were indicated. Forty-two participants indicated haloperidol as their first choice. Alprazolam, diazepam risperidone and quetiapine were chosen by 15, 9, 1 and 1 of the participants, respectively. These numbers were summed up (N=26). The results revealed that, even though all other medications were considered together, the choice of haloperidol (N=42) was greater than the choice of all the other medications (N=26); and this effect was marginally significant [χ 2 (1,N=68)=3.77, p=.052]. Table III: Medications used by the the residents for the control of delirium symptoms Haloperidol 85.3% Lorazepam, olanzapine, diazepam 41.3% Alprazolam 38.7% Risperidone 16% Quetiapine 6.7% Midazolam 6.7% DISCUSSION In our study, we observed that most of the diagnose of delirium and decision-making processes were limited to the hyperactive form of the delirium. Often, the silent or hypoactive forms of delirious states where lethargy and psychomotor retardation are the main symptoms, were not properly recognized in hospital settings. In an earlier study conducted in a sample of 38 inpatients, the hyperactive delirium rate was 80.45% and hypoactive delirium rate was 16.12% 12. This figure seems to represent a far lower delirium rate than expected and should therefore be revised. These result represented a retrospective analysis of the delirium patients and only covered the hyperactive forms. One of the leading causes might be the underdiagnosis of delirium or the lack of interdisciplinary collaboration during its management. In an earlier case study, two major problems associated with the lack of recognition of delirium were underlined as lack of knowledge on the part of the nurses about the criteria and methods for detecting delirium and the ineffective communication between staff members in relaying symptoms of the onset of the clinical condition 6. Our results confirm both findings. We believe that nurses and residents in daily care needed to be more careful about the correct diagnosis. Delirium or an acute confusional state, which, most of the time, is a result of hospitalrelated complications or hospital care, can be seen as a marker of the quality of hospital care. Failure to recognize delirium in its early stages is one of the leading pathways leading to an increase in the incidence of delirium 9. Examining delirium can also provide an opportunity to improve the quality of hospital care and associated services. Nursing staff play an important role in supporting the clinical decision process in this sense. Unlike other studies, family members seem to participate in the daily clinical routine as one of the main sources of clinical information in Turkey. Despite their impact on daily routine, they are often neglected in terms of sharing clinical information. Short training sessions or information cards might improve their participation and better recognition and follow-up of delirium. Situated clinical reasoning, incorporating decision support research might support best practice clinical pathways and clinical reasoning in the treatment of delirium. Studies on teaching critical clinical decision skills showed that undergraduate interventions were more effective than resident interventions 13. These results also show that delirium should be an important curriculum item in internship training in medical schools. Delirium has only a limited coverage in the medical curriculum and most of the clinical priorities develop in medical practice. This result is also reflected in our findings: most of the priorities of clinical decisions and treatment focused mainly on clinical experience. Overall, the clinicians responded parallel to delirium guidelines concerning the clinical diagnosis and treatment. Current information on delirium has limited space in clinical practice. For example, the effect of medication was little covered in our study. In our earlier study in Marmara University Hospital, we demonstrated that the mean drug number per case of delirium patients was as high as 6.69 12. We believe that a more focused curriculum on 103

Marmara Medical Journal 2004;17(3);99-104 M.Kemal Kuşcu, et al. Attitudes and Priorities of Training Clinicians in Diagnosing Delirium in An Academic Hospital delirium in medical school and further training during residency and in-house service could support good clinical practice in delirium. The study was conducted in adult inpatient wards. Yet, delirium in specific need groups is one of the main focuses of recent delirium research due to the high prevalence and mortality rates. For that reason, delirium in chemotherapy, elderly and critical care patients remains an important issue and should be addressed in future research 14-16. Similarly, delirium in other specific need groups such as children has not been researched in detail and remains an important clinical agenda 17. One of the important aspects of the current study is to promote application of the study findings to clinical settings. Delirium still remains an important clinical emergency in clinical practice. We hope this study will promote further insight for daily clinical routines in Marmara University Hospital. We believe such effort will provide ground to develop new consensus guidelines for management of delirium, which will improve the outcome and treatment process of this clinical condition. REFERENCES 1. Diagnostic and Statistical Manual of Mental Disorders- Fourth edition. Washington, DC: American Psychiatric Association,1994:123-133. 2. Wise MG, Trzepacz P. Delirium (Confusional States). In: Rundel RJ, Wise MG, eds. Textbook of Consultation Liaison Psychiatry. Washington, DC: The American Psychiatric Publishing,1996:259-274. 3. Smith L, Dimsdale J. Postcardiotomy delirium: conclusion after 25 years. Am J Psychiatry 1989;146: 452-458. 4. Gustafson Y, Berggren D, Brannstrom B. Acute confusional states in elderly patients treated for femoral neck fracture. J Am Geriatr Soc 1988;36:525-530. 5. Johnson J. Identifying and recognizing delirium. Demen Geriatr Cogn Disord 1999;10: 353-358. 6. Eden BM, Foreman MD. Problems associated with underrecognition of delirium in critical care: A case study. Heart & Lung 1996;25:388-400. 7. Weddington WW. The mortality of delirium: an underappreciated problem. Psychosomatics 1982;23:1232-235. 8. Young LJ, George J. Do guidelines improve the process and outcomes of care in delirium? Age Ageing. 2003;32:525-528. 9. Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med 1999;106:565-573. 10. Bornsteşin BH, Emler AC, Chapman GB. Rationality in medical treatment decisions: is there sunk-costeffect? Soc Sci Med 1999;49: 215-222. 11. Lacko L, Bryan Y, Dellasega C, Salerno F. Changing clinical practice through research: the case of delirium. Clin Nurs Res 1999;8:235-250. 12. Kuşcu MK, Topçuoğlu V, Altunel Ö, Bez Y. Deliryum tanısıyla takip edilen hastaların izlem sonuçları. Anadolu Psikiyatri Dergisi 2004;5:16-21. 13. Norman GR, Shannon SI. Effectiveness of instruction in critical appraisal (evidence-based medicine) skills: a critical appraisal. CMAJ 1998;158:177-181. 14. Ljubisavljevic V, Kelly B. Risk factors for development of delirium among oncology patients. Gen Hosp Psychiatry. 2003;25:345-352. 15. McCarthy MC. Detecting acute confusion in older adults: Comparing clinical reasoning of nurses working in acute, long-term, and community health care environments. Res Nurs Health 2003;26:203-212. 16. Litton KA. Delirium in the critical care patients: what the professional staff needs to know. Crit Care Nurse 2003;26:208-213. 17. Manworren RC, Paulos CL, Pop R. Treating children for acute agitation in the PACU: differentiating pain and emergence delirium. J Perianesth Nurs 2004; 19:183-193. 104

ORIGINAL RESEARCH RELATION OF SERUM S-100 PROTEIN TO INFARCT SIZE AND CLINICAL PROGNOSIS Gülay Kenangil 1, A.Destina Yalçın 1, Gonca Haklar 2, Hasan Cacina 2, Hulki Forta 1 1 Neurology Clinic,Şişli Etfal Education and Research Hospital, Istanbul, Turkey 2 Department of Biochemistry, School of Medicine, Marmara University, Istanbul, Turkey ABSTRACT Objectives: To analyze serum concentrations of S-100 protein in acute ischemic stroke and to determine its correlation to infarct size and clinical prognosis. Methods: Serum samples were collected from 26 acute ischemic stroke patients on admission and on the third and seventh days. Serum S-100 protein levels were measured using Smart S-100 protein detection reagent. The lesions were classified as supratentorial middle cerebral artery infarctions and infratentorial brainstem infarctions. All patients had cranial computerized tomography (CT) scan in the first 24 hours and magnetic resonance imaging (MRI) or CT scan in the first week. Neurological evaluation was made with the National Institute of Health Stroke Scale (NIHSS) in the acute stage and with Modified Barthel Index (MBI) in the 1st and 6th months. ANOVA was used for statistical analysis. Results: MCA infarctions greater than 2/3 of MCA territory had highest S100 protein levels on day 3, greater scores on NIHSS and smaller scores on MBI. Serum S-100 was undetectable in the infratentorial infarction group. Conclusion: S-100 protein is correlated with the infarct size and prognosis in MCA lesions and its rise on the 3rd day may reflect edema. Keywords: S-100 protein, Ischemic stroke, Prognosis,Iinfarct size SERUM S-100 PROTEİNİNİN ENFARKT BOYUTU VE KLİNİK PROGNOZ İLE İLİŞKİSİ ÖZET Amaç: Akut iskemik inmelerde serum S-100 protein konsantrasyonlarının ölçülmesi ile enfarkt boyutu ve klinik prognoz ile olan korelasyonlarının belirlenmesi Yöntemler: Serum örnekleri 26 akut iskemik inmeli olgudan başvuru sırasında, 3. ve 7. günlerde toplandı. Serum S-100 protein düzeyleri Smart S-100 protein saptama reaktifi ile ölçüldü. Lezyonlar supratentoryal orta serebral arter (middle cerebral artery, MCA) enfarktları ve infratentoryal beyin sapı enfarktları olarak sınıflandırıldı. Tüm hastaların ilk 24 saat içinde çekilmiş kraniyal kompüterize tomografileri (computerized tomography, CT) ve ilk hafta içinde çekilmiş manyetik rezonans görüntülemeleri veya CT leri mevcuttu. Nörolojik incelemeleri akut evrede National Institute of Health Stroke Scale (NIHSS) ile, 1. ve 6. aylarda Modified Barthel Index (MBI) ile yapıldı. İstatistiksel analizlerde ANOVA kullanıldı. Bulgular: MCA bölgesinin 2/3 ünden fazlasını tutan MCA enfarktları 3. günde en yüksek S-100 protein değerlerine, en yüksek NIHSS ve en düşük MBI skorlarına sahipti. İnfratentoryal enfarkt grubunda serum S-100 proteini ölçülemez düzeydeydi. Sonuç: MCA lezyonlarında S-100 proteini enfarkt boyu ve klinik prognoz ile ilişkilidir ve 3. gündeki artış ödem göstergesi olabilir. Anahtar Kelimeler: S-100 proteini, İskemik inme, Prognoz, Enfarkt boyutu INTRODUCTION Neurobiochemical markers of brain damage gained particular attention in the identification of stroke in recent years. S-100 protein is a dimeric, acidic calcium binding protein (MW: 21,000 daltons) which is a major component of the cytosol particularly in astroglial cells. The protein is metabolized and eliminated by the kidney, its biological half-life is approximately 2 hours 1-2. S- 100 protein has two subunits, S-100 B and S-100 A 3. S-100 protein B fraction has been shown to Corresponding author: Gülay Kenangil Yeni Çamlıca Mah. Duman Sok. No: 50.7000 A Konutları 3/20 Umraniye, Istanbul, Turkey. E-mail: kenangil@superonline.com exhibit regulatory effects on cell growth and differentiation as well as on cell shape and energy metabolism 4. In previous studies, the elevation of S-100 B protein in cerebrospinal fluid (CSF) was reported in various conditions, including acute cerebral damage such as head trauma, cerebral hypoxia, cerebral bleeding and ischemic stroke 5-7. The difficulty of collecting CSF samples by lumbar puncture urged investigators to study such biochemical markers in blood. In this study we have aimed to evaluate whether serial Marmara Medical Journal 2004;17(3);105-108 105

Marmara Medical Journal 2004;17(3);105-108 Gülay Kenangil, et al. Relation Of Serum S-100 Protein To Infarct Size and Clinical Prognosis measurements of blood S-100 B protein level correlate with the infarct size and the clinical prognosis in acute ischemic stroke. METHODS The study was approved by the Ethical Committee of Marmara University Medical Faculty. S-100 B serum levels were determined in 26 patients with acute ischemic stroke (15 men, 11 women; mean age 65.1 ± 13.35) admitted to our hospital within the first 24 hours of stroke onset. Patients were classified according to the size and localization of the infarcts as, supratentorial large middle cerebral artery (MCA) infarctions greater than 2/3 of MCA territory (n=6), medium MCA infarctions between 1/3 to 2/3 of MCA territory (n=7), small MCA infarctions smaller than 1/3 of MCA territory (n=6), and infratentorial brainstem infarctions (n=7). The localization of infarcts was made by vascular mapping of Tatu and his friends 8. All patients had neurological examination and cranial CT scan in the first 24 hours and cranial CT or MRI in the first week. Blood samples were collected on admission and on the third and seventh days. S-100 B protein levels were measured by an ELISA method (Smart S-100 protein, Skye Pharma Tech. Inc, Canada). Neurological evaluation was made by National Institute of Health Stroke Scale (NIHSS) in the acute stage and by Modified Barthel Index (MBI) on the first and sixth months. NIHSS scores were as follows: 1-7 mild neurological deficit, 8-14 moderate neurological deficit, 15 severe neurological deficit. In MBI the maximum score was 20, meaningfull independency. Score 0 was the worst, meaning full dependency. Statistical analyses were made using the Instat 2.0 programme. Data were given as mean ± SEM. Repeated measures of ANOVA with Tukey- Kramer Multiple comparison test was used for the statistical analysis and the differences were considered significant when probability was p < 0.05. One of our patients with large MCA infarction died on the 10 th day of admission because of heart failure. (We were able to take his blood samples.) His NIH score was 19 and his MBI score was accepted as zero for both the first and the 6 th month. RESULTS Patients were divided into 4 groups according to localization and size of the lesion seen on the CT or MRI. Groups were as follows: Large MCA infarctions (greater than 2/3 of MCA territory, Table I), medium MCA infarctions (1/3-2/3 of MCA territory), small MCA infarctions (smaller than 1/3 of MCA territory), and infratentorial brainstem infarctions (Table II). Five of the brainstem lesions were in pons, located in paramedian region and greater than 1.5 cm. The other two lesions were very large and one of them was located along both lateral medulla and cerebellum. The other had scattered lesions in pons, midbrain and thalamus. Serum S-100 protein levels are given in Table III. Serum S-100 B protein was undetectable in the brainstem infarctions. In large MCA infarctions serum S-100 B protein concentration was significantly higher in 3 rd day samples when compared to samples taken on admission (p<0.05). However, there was no difference between levels on admission and at 7 th day or 3 rd and 7 th day samples. There was no statistical significance between S-100 B levels on admission, at 3 rd day and/or 7 th day for patients with medium and small MCA infarctions. There were significant correlations between S-100 protein concentrations and MBI scores in large MCA infarctions (p<0.05 for both first and sixth month evaluations) but the correlation between S- 100 protein concentrations and NIHSS was not significant. Table I: Data on large MCA infarctions Patients Age Gender National Institute of Health Stroke Scale Modified Barthel Index (First month) 1 58 M 19 0 0 2 68 M 19 0 0 3 81 W 14 0 0 4 98 M 16 0 0 5 62 M 18 8 12 6 63 W 17 9 12 Modified Barthel Index (Sixth month) 106

Marmara Medical Journal 2004;17(3);105-108 Gülay Kenangil, et al. Relation Of Serum S-100 Protein To Infarct Size and Clinical Prognosis Table II: Data on Brainstem infarctions Patient No. Age Gender National Modified Barthel Modified Barthel Institute of Index (First Index (Sixth Health Stroke month) month ) Scale 20 78 M 8 15 20 21 51 W 5 20 20 22 63 M 13 16 20 23 57 M 0 20 20 24 47 M 3 20 20 25 61 W 6 20 20 26 35 W 3 20 20 Table III: Serum S-100 levels (ng/l) in MCA infarctions Day 0 Day 3 Day 7 Large MCA infarctions (n=6) 18 ± 7 114 ± 29 *,** 40 ± 19 Medium MCA infarctions (n=7) 12 ± 5 13 ± 7 5 ± 2 Small MCA infarctions (n=6) 1 ± 0.4 1.5 ± 0.8 3.3 ± 2.4 DISCUSSION Many markers of ischemic brain damage such as S-100 B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) have been investigated after acute ischemic stroke 9-10. Persson et al. 11 were the first to study S-100 protein in blood and found elevations in two patients. Elevation of serum S- 100 protein B levels in acute stroke observed in our study were in accordance with a number of reports in the literature 12-14. Kim et al. 13 found S- 100 protein B in 11 patients who had either large ischemic or hemorrhagic stroke. They found S- 100 peak on the third day in patients with large ischemic stroke and on the first day in patients with hemorrhagic stroke. Herrmann et al. 14 compared S-100 B and GFAP serum concentrations after stroke and found that release of both markers was associated with the volume of brain lesions and the neurological status at discharge from the hospital. Missler et al. 15 studied 44 patients and found good correlation between peak S-100 protein level in plasma and clinical outcome after 6 months. This was the first study to report an association between a single biochemical marker from blood in the acute phase of stroke and functional outcome of infarction. They concluded that the concentration of S-100 protein in blood during acute stroke was a useful marker of infarct size and of long-term clinical outcome 15. Büttner et al. 12 studied serum S-100 protein levels after MCA infarctions in relation to clinical data and prognosis. Patients with extensive ischemic edema (rather than patients with small lesions) were characterized by high S- 100 levels in serum. In our study we evaluated the infarctions in MCA territory and divided them into 3 groups according to their size. Patients with large MCA infarctions had the highest serum S- 100 levels on day 3 and their short and long-term prognosis were the worst of all. According to our knowledge large MCA infarctions had maximum edema on day 2 and 3, therefore we agree with Büttner that S-100 levels can reflect cerebral edema. Smaller artery groups had no significant rise in serum S-100 on day 0, 3 or 7. In large MCA infarctions there was no significant correlation between third day S-100 values and NIHSS but there was a statistically significant correlation between third day S-100 values and the first and sixth month MBI. The prognosis was the worst in large MCA infarctions and they had the smallest scores in MBI. Therefore, we conclude that in large ischemic infarctions MBI is a good index for showing the clinical prognosis. In more recent reports Wunderlich et al. 16 reported that patients with cerebellar or brainstem lesions showed better functional outcome at discharge from the hospital. In our infratentorial infarction group, lesions with different size were located in different infratentorial areas. 107

Marmara Medical Journal 2004;17(3);105-108 Gülay Kenangil, et al. Relation Of Serum S-100 Protein To Infarct Size and Clinical Prognosis Interestingly no elevation of serum S-100 protein was found in any of them. They all had good short and long term prognosis. We believe that this observation requires further investigation. The small sample size of this study may be the shortcoming of it.. Recent reports about S-100 B measurements in malignant MCA infarctions also supported that S-100 B values elevations in acute stroke reach maximum levels in 2 to 4 days after stroke 17,18. Foerch et al reported that a single S- 100 B measurement performed 12 to 24 hours after symptom onset could predict the development of the malignant MCA infarctions and it could be used as a valuable marker in guiding clinical and therapeutic desicions for this life- threatening stroke 17. Finally we conclude that serum S-100 B measurement can be used as an early marker of brain damage. It is correlated with the size of the lesion in MCA infarctions and may reflect cerebral edema. Serum S-100 protein B levels may also be used as a prognostic marker. Large sample sized studies are needed. REFERENCES 1. Martens P, Raabe A, Johnsson P. Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia. Stroke 1982; 9: 2363-2366. 2. Heizmann WC. Ca-binding S-100 proteins in the central nervous system. Neurochem Res 1999; 24: 1097-1100. 3. Heizmann WC, Cox JA. New perspectives on S-100 proteins: a multifunctional Ca +2 -Zn +2 and Cu +2 binding protein family. Biometals 1998; 11: 383-397. 4. Schmidt S. S-100 B: pathogenetic and pathophysiologic significance in neurology. Nervenarzt 1998; 69: 639-646. 5. Hardemark HG, Erricson N, Kotwica Z, et al. S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage. J Neurosurg 1989; 71: 727-731. 6. Makuno K, Kato K, Kawai K, Matsuoka Y, Yanagi T, Sobue I. Neuron-specific enolase and S-100 protein levels in cerebrospinal fluid of patients with various neurological diseases. J. Neurol Sci 1983; 60: 443-451. 7. Lamers KJ, van Engelen BG, Gabreels FJ, Hommes OR, Borm GF, Wevers RA. Cerebrospinal neuron-spesific enolase, S-100 and myelin basic protein in neurological disorders. Acta Neurol Scand 1995; 92: 247-251. 8. Tatu L, Moulin T, Bogousslavsky J, Duvernoy H. Arterial territories of the human brain, cerebral hemispheres. Neurology 1998; 50: 1699-1708. 9. Butterworth RJ, Wassif WS, Sherwood RA,Gerges A. Serum NSE, carnosinase, and their ratio in acute stroke: an enzimatic test for predicting outcome? Stroke 1996; 27: 2064-2068. 10. Engelen BG, Lamers KJ, Gabreels FJ, Wever RA, van Geel WJ, Borm GF. Age-related changes of neuron specific enolase, S-100 protein and myelin basic protein concentration in cerebrospinal fluid. Clin Chem, 1992; 38: 813-816. 11. Persson L, Hardemark HG, Gustafsson J et al. S-100 protein and neuron specific enolase in cerebrospinal fluıd and serum: markers of cell damage in human central nervous system. Stroke 1987; 18: 911-918. 12. Büttner T, Weyers S, Postert T. S-100 Protein: serum marker of focal brain damage after ischemic territorial MCA infarction. Stroke 1997; 28: 1961-1965. 13. Kim JS, Yoon SS, Kim YH,Ryu JS. Serial measurement of interleukin-6, transforming growth factor-b and S- 100 protein in patients with acute stroke. Stroke 1996: 27; 1553-1557. 14. Herrmann M, Vos P, Wunderlich MT, Bruijn CHMM, Lamers KJB. Release of glial tissue-specific proteins after acute stroke. A comparative analysis of serum concentrations of protein S-100 B and glial fibrillary acidic protein. Stroke 2000; 31: 2670-2677. 15. Missler U, Wiesmann M, Friedrich C, Kaps M. S-100 Protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. Stroke 1997; 28: 1956-1960. 16. Wunderlich MT, Ebert AD, Kratz T, Goertler M, Jost S, Hermann M. Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage. Stroke 1999; 30: 1190-1195. 17. Foerch C, Otto B, Singer O C, Haefelin T N, Yan B, Berkefeld J, Steinmetz H et al. Serum S-100 B predicts a malignant course of infarction in patients with acute middle cerebral artery occlusion. Stroke 2004; 35: 2160-2164. 18. Foerch C, Singer O C, Haefilin TN, Rochemont M, Steinmetz H. Evaluation of Serum S-100 B as a surragate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction. Arch Neurol 2005 ;62: 1130-1134. 108

ORIGINAL RESEARCH SHOULD CHILDREN WITH ISOLATED PREAURICULAR TAGS BE ROUTINELY EVALUATED FOR ASSOCIATED RENAL AND CARDIAC MALFORMATIONS? Cigdem Ulukaya Durakbasa 1, Murat Mutus 1, Ferhan Meric 2, Elif Sirlioglu 3, Yusuf Ayhan 2, Savas Dedeoglu 2, Varol Sehiralti 1, Nadir Tosyali 1, Nurten Andac 3 1 Pediatric Surgery Clinic, SB İstanbul Göztepe Hospital. Istanbul, Turkey 2 Cardiology Clinic, SB Istanbul Goztepe Hospital, Istanbul, Turkey 3 Radiology Clinic, SB Istanbul Goztepe Hospital,Istanbul, Turkey ABSTRACT Objective: The aim is to assess the rate of coexistence of renal and cardiac anomalies in children with isolated preauricular tags and to determine whether routine evaluation for such associated malformations is warranted. Methods: All children presented to the outpatients clinic with the complaint of isolated preauricular tag were prospectively included in the study between the years 1995-2004. Syndromic children were excluded. Urinary tract ultrasonography (USG) and cardiac evaluation were employed in all. Results: The study included 46 children. The median age was 36 months (range, 2 months to 10 years), excluding four newborn. There were 30 (65%) males and 16 (35%) females. USG examination revealed two (4%) patients with pelvicalyceal dilatation, one of which resolved spontaneously. The other patient proved to have a ureteropelvic junction obstruction and underwent corrective surgery. Cardiac evaluation yielded an atrial septal defect in one (2%) child. Another one had Wolf-Parkinson-White Syndrome which is not a congenital cardiac malformation but rather a pre-excitation syndrome. Conclusion: The present study supports the data favoring routine use of USG to evaluate UT in children with isolated preauricular tags. However, more prospective studies incorporating larger sample sizes are needed before offering routine cardiac evaluation in these children. Keywords: Preauricular, Tag, Trag, Renal, Cardiac, Children İZOLE PREAURİKULAR TRAGUSU OLAN ÇOCUKLARDA EŞLİK EDEN BÖBREK VE KALP MALFORMASYONLARI RUTİN OLARAK ARAŞTIRILMALI MIDIR? ÖZET Amaç: Bu çalışmanın amacı izole preaurikular tragusu olan çocuklarda eşlik eden böbrek ve kalp malformasyonlarının görülme sıklığınının belirlenmesi ve buna yönelik rutin inceleme yapılmasının gerekliliğinin ortaya konmasıdır. Gereç ve Yöntem: 1995-2004 yılları arasında çocuk cerrahisi polikliniğine izole preaurikular tragus yakınması ile başvuran ve sendromik olmayan tüm çocuklar prospektif olarak çalışmaya dahil edilmiştir. Bütün çocuklara üriner sistem ultrasonografisi (USG) uygulanmış; ayrıca kardiak değerlendirme yapılmıştır. Bulgular: Çalışmaya 46 çocuk dahil olmuştur. Bu çocukların 4 ü yenidoğandır. Yenidoğanlar hariç tutulduğunda, ortanca yaş 36 aydır (dağılım, 2 ay ile 10 yıl). Çocukların 36 sı (%65) erkek, 16 sı (%35) kızdı. USG ile pelvikaliseal sistemde genişlemesi olan 2 (%4) hasta tespit edildi. Bunların birinde bulgular kendiliğinden gerilerken diğer hastada üreteropelvik bileşke darlığı tespit edilerek düzeltici ameliyat yapıldı. Kardiak değerlendirme sonucunda 1 (%2) hastada atrial septal defekt tespit edildi. Doğumsal bir kalp malformasyonu olmamakla beraber, bir başka çocukta da Wolf-Parkinson-White sendromu bulundu. Sonuç: Mevcut çalışmada elde edilen sonuçlar izole preaurikular tragusu olan çocuklarda üriner sistemin değerlendirilmesine yönelik olarak rutin USG önerilmesini desteklemektedir. Ancak, bu çocuklarda kardiak değerlendirmenin rutin olarak yapılmasını önermeden önce, yapılacak daha fazla prospektif çalışma ile olgu sayısının artırılması gerekmektedir. Anahtar Kelimeler: Preaurikular, Trag, Tragus, Renal, Kardiak, Çocuklar INTRODUCTION Preauricular tags are accessory tags ( trags ) located in the pretragal region. Such tags may be found anywhere along an imaginary line drawn Corresponding author: Cigdem Ulukaya Durakbasa, M.D., Pediatric Surgery Clinic, SB İstanbul Göztepe Hospital, Göztepe, İstanbul, Turkey. E-mail: cigdemulukaya@yahoo.com from the tragus to the angle of the mouth or along the anterior margin of the sternocleidomastoid muscle 1. They are relatively common congenital anomalies with a prevalence of about 5-10 per 1000 live births and are the most common form of Marmara Medical Journal 2004;17(3);109-112 109

Marmara Medical Journal 2004;17(3);109-112 Cigdem Ulukaya Durakbasa, et al. Should Children with Isolated Preauricular Tags be Routinely Evaluated For Associated Renal and Cardiac Malformations? all external ear abnormalities 2. They may be either isolated or found in association with some congenital syndromic anomalies. In general, isolated tags are regarded as cosmetically important. However, there are previous reports that indicate the presence of associated renal anomalies and hearing impairment in these children 3-5. On the other hand, the possible association of cardiac anomalies in nonsyndromic children with isolated tags is not extensively studied. Moreover, such probable associations in cases with isolated tags have not been documented in Turkish population. This prospective study was performed to assess the coexistence of cardiac and renal anomalies and determine whether routine cardiac evaluation together with urinary tract (UT) ultrasonography (USG) is indicated in children with isolated preauricular tags. with bilateral preauricular tags. A positive family history in the first degree relatives was found in 2 (4%) patients. Physical examination revealed a left undescended testis (UDT) in a child with a left-sided tag and a rectal polyp in another one who had history of intermittent rectal bleeding. METHODS The study group included all children presented to the pediatric surgical outpatients clinic with the complaint of preauricular tag that is not associated with a pit or dysplastic ear between the years 1995-2004. A systemic examination was performed in all children. The study included only healthy infants and syndromic children who had preauricular tag as a part of other systemic malformation(s) were excluded. USG (3,5-5 MHz, GE Logiq 5 PRO, GE, Milwaukee) examination was performed by a radiologist in the radiology department. Cardiac evaluation was done by pediatric cardiologists and included a physical examination, telegraphy of chest and electrocardiography. Additionally, a comprehensive echocardiographic examination with pulsed, continuous, color Doppler was performed with a Hewlet-Packard Sonos 1000 Ultrasound System (Hewlet-Packard Co., Palo Alto, California), using a 3.5-5 MHz transducer. RESULTS During the study period, 46 children with isolated preauricular tags presented to the outpatients clinic of our institution. There were four newborns. The median age was 36 months (range, 2 months to 10 years), excluding the newborns. There were 30 (65%) males and 16 (35%) females. Tags were located on the right side in 10 (22%) patients and on the left side in 14 (30%) (Fig. 1). They were bilateral in 22 (48%) patients. There was an additional facial tag in an infant Fig. 1: Isolated left-sided solitary preauricular tag (arrow) An informed consent was obtained for each patient. Renal USG was normal in 44 patients, whereas, it revealed right-sided pelvicalyceal dilatation in two (4%). One of them was the patient who also had left UDT. He was aged 10 days at the time of the initial USG examination and dilatation disappeared spontaneously three months later. However, further diagnostic evaluation in the other, 8-month-old girl with bilateral tags revealed a ureteropelvic junction obstruction (UPJO). She was operated on for relieving the obstruction with a successful surgical outcome. Cardiac evaluation yielded abnormal findings in two other children (4%), isolated secundum type atrial septal defect (ASD) in one and Wolf- Parkinson-White (WPW) syndrome in the other. The boy with ASD was aged 2 months old and had bilateral tags. The other patient was an asymptomatic 5-year-old boy with a solitary leftsided tag. No surgical intervention was necessary and both children are being followed up in the department of pediatric cardiology. DISCUSSION Preauricular tags represent accessory hillock of His, the hillocks that normally develop in the 110

Marmara Medical Journal 2004;17(3);109-112 Cigdem Ulukaya Durakbasa, et al. Should Children with Isolated Preauricular Tags be Routinely Evaluated For Associated Renal and Cardiac Malformations? recess of the mandibular and hyoid arches and coalesce to form the auricle 4. Clinically, they are soft or firm, small, skin-colored nodules, usually containing a cartilage core. Preauricular tags are the most common form of external ear malformations and are usually unilaterally located 1. Contrary to literature data, in almost half of the presented cases the tags were bilateral. However, the reason for this difference is obscure. There was a male predominance in the present report and a positive family history could be obtained in a small percent of cases. Coexistence of renal and auricular malformations can be seen in various congenital syndromes and associations. Therefore, it is agreed that accompanying dysmorphic features in a patient with isolated preauricular tag should alert the clinician for a through systemic investigation 6. However, the present study included only the non-syndromic children who had no dysmorphic features but only isolated tags where a consensus regarding further evaluation has not been reached. It is known that the incidence of UT malformation severe enough to warrant surgery in the normal population is approximately 1% 7. Although the need for UT evaluation in non-syndromic children with major external ear malformations is well accepted, the issue is controversial for children with minor malformations including isolated preauricular tags 2. Kohelet et al examined 70 consecutive infants with isolated preauricular tags and detected UT abnormalities in 6 (9%) of them 5. There was hydronephrosis either due to UPJO or vesico-ureteric reflux in 5 and horseshoe kidney in one. Likewise, Mishra et al found a UT abnormality incidence of 9% out of 34 patients with isolated preauricular tag 4. There were two patients with unilateral hydronephrosis and one with double renal pelvis. Contrary to these reports, in a study performed in 108 infants with isolated preauricular tags or pits the prevalence of UT abnormalities detected on USG was not different from that of control group 6. In a recent study, where 96 consecutive infants with isolated minor malformations of external ear were examined by renal USG, only 1 infant (1%) had transient unilateral pyelectasia 8. The authors, therefore, concluded that routine renal imaging is not warranted in infants with minor external ear malformations unless accompanied by other systemic findings. Congenital cardiac disease occurs in 0.5-0.8% of live births 9. It has long been known that congenital cardiac defects can be associated with anomalies of the renal system and external ear 10. There are several well-known syndromes, like Goldenhar syndrome (oculo-auriculo-vertebral dysplasia), where congenital cardiac disease coexists with external ear malformations. In the etiology, a relatively synchronous embryonic insult might be taking place that affect the simultaneous development of both heart and ear; but the precise mechanism for this association is obscure 10. On the other hand, in a prospective study of 523 non-syndromic infants with external ear anomalies of all types, it was postulated that the prevalence of congenital cardiac disease rate was increased three-fold in children with ear anomalies in comparison with general population 11. Therefore, on clinical grounds, cardiac evaluation can be offered in children with nonsyndromic, isolated preauricular tags. There were two children diagnosed to have cardiac anomaly in the current study, although one of the diagnoses, namely, WPS syndrome is not classified under the heading congenital cardiac diseases 9. Actually, it is the most common form of cardiac pre-excitation syndromes with an estimated overall prevalence of 0.1-0.3% among the general population 12. Although the cause is not known, it may be associated with congenital heart disease, hypertrophic cardiomyopathy or tuberous sclerosis. The presented case had no other association detected and is currently being followed up on medication. Isolated secundum ASDs account for 7% of congenital cardiac defects 9. They are usually asymptomatic throughout childhood and may close spontaneously. In the present study, there is an age disparity among the patients at the time of USG examination or cardiac evaluation. This is a limitation in ascertaining the exact incidence of associated anomalies because USG findings like pelvicalyceal dilatation in early life may resolve as the child gets older. Likewise, some noncyanotic cardiac lesions like ASDs detected in term newborns may close spontaneously. Some form of UT anomaly was detected in 2 (4%) children in the present study but only 1 (2%) needed corrective surgery. The number of patients is limited to make comparisons with the general population s surgical UT anomaly prevalence of 1%. Therefore, a strict conclusion cannot be withdrawn. However routine UT USG as a noninvasive imaging modality can still be offered in children with isolated preauricular tags until controversies in the reported data resolve. Similarly, the sample size of the present study is too small to offer a routine cardiac evaluation in 111