The History of Clinical Drug Trials in Turkey The history of clinical trials in Turkey dates back to the beginning of the 20th century, but many years had passed with studies done with no compliance to the Good Clinical Practice (GCP) guidelines. This was not due to the lack of legal documents. On the contrary, the first mention of clinical trials in a legal document occurred in 1926; “The Code of Pharmaceutical Products and Preparations No. 1262” law carried the statement: “Experimental drugs can be used in a patient only by his/her permission.”

Abstract | Full Text PDF

Ýnsan baðýþýkyetmezlik virusu (HIV), Hepatit B ve Hepatit C virüslerinin neden oduðu infeksiyonlar halen önde gelen en önemli saðlýk problemi olmaya devam etmektedir. HBsAg, anti-HCV, anti-HIV ve VDRL gibi tarama testleri kan ürünleri veya kan transfüzyonlarýndan önce bakýlmasý zorunlu testlerdir. Bu çalýþmada, kan merkezimize 9 yýl içinde baþvuran dönorler HBsAg, anti-HCV, anti-HIV ve sifiliz seroprevalansý açýsýndan retrospektif olarak deðerlendirildi. HBsAg, anti-HCV, anti-HIV ELÝSA mikropartikül sistemi ile incelenirken sifiliz antikorlarý ise sifiliz test cihazý ile tarandý. Toplam 39.002 kiþiden 16.602 (%42)’si kadýn ve 22.401 (%58)’i de erkekti. HBsAg, tüm donörlerin %2.55’inde pozitif olarak bulunurken, anti-HCV, anti-HIV ve VDRL pozitifliði sýra ile tüm dönorlerin %0.17, %0.036, %0.057’sinde pozitifti. Sonuç olarak bölgemizde yaþayan donörlerdeki HBsAg, anti-HCV, anti-HIV ve VDRL seropozitifliði Türkiye’de bulunan çoðu bölgelerdekinden daha düþük bulundu. Yine de transfüzyondan kaynaklanan riskleri azaltýp sýfýra indirecek her hangi bir tarama metodu bulunmamasý nedeni ile, gereksiz transfüzyonlardan kaçýnýlmasýna ve donör seçiminde daha dikkatli davranýlmasýna ihtiyaç vardýr.

Infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency viruses (HIV) remain the leading most important health problems worldwide. Screening tests such as HBsAg, anti-HCV, anti-HIV and VDRL are mandatory tests to look at before transfusion of blood or blood components. In this study, donors who applied to our Blood Center in a nine-year period were retrospectively evaluated with respect to HBsAg, anti-HCV, anti-HIV and syphilis seroprevalence. HBsAg, anti-HCV and anti-HIV were examined by microparticle ELISA system, and syphilis antibodies were screened by a syphilis test device. Of the total 39,002 individuals, 16,601 (42%) were females and 22,401 (58%) were males. HBsAg positivity was found in 2.55%, anti-HCV in 0.17%, anti-HIV in 0.036%, and VDRL in 0.057% of overall donors. As a result, HBsAg, anti-HCV, anti-HIV and VDRL seropositivity rates in donors living in our region were found lower than those in many regions of Turkey. Nevertheless, because there is no screening method to reduce the risk resulting from transfusion to zero, it appears that it is essential to adopt strict criteria in the selection of donors and to avoid unnecessary transfusion.

Abstract | Full Text PDF

Bu çalýþmaya akut lösemi tanýsý almýþ ve en az 5 yýldýr remisyonda olan 28 hasta (10 kýz, 18 erkek) dahil edildi ve bu olgularda endokrin yan etkiler araþtýrýldý. Yirmibeþ hasta akut lenfoblastik lösemi, 3 hasta akut non-lenfositik lösemi tanýsý almýþtý. Onaltý çocuðun tedavisinde BFM-90 tadavi protokolü kullanýlýrken diðerleri farklý tedavi rejimleri aldýlar. Ýki hastaya 12-13 Gy total vücut ýþýnlamasý sonrasý kemik iliði transplantasyonu uygulandý. Yirmisekiz hastadan birinde (%3) boy kýsalýðý, dördünde (%14) obezite mevcuttu. Hastalarýn ikisinde (%7) gecikmiþ puberte, ikisinde glukoz intoleransý, birinde sekonder hipotroidizm ve ikisinde de hipergonadotropik hipogonadizm saptandý. Bir olguda TRH testine abartýlý TSH yanýtý, 3 olguda baskýlanmýþ yanýt gözlendi.

This study was carried out in 28 patients (10 female, 18 male) diagnosed with acute leukemia, and aimed to investigate the abnormalities of endocrine system. Twenty-five of 28 patients were acute lymphoblastic leukemia and 3 were acute non-lymphocytic leukemia. Sixteen children were treated using BFM-90 chemotherapy protocol, and the rest with various regimens. Two patients were exposed to 12-13 Gy of total body irradiation followed by bone marrow transplantation. All patients were in remission at least five years. One (3%) of 28 patients had short stature and 4 (14%) had obesity. Pubertal status was retarded in 2 (7%) patients. Glucose intolerance, secondary hypothyroidism and hypergonadotropic hypogonadism were detected in 2, 1 and 2 patients, respectively. TSH response to TRH test was exaggerated in 1 and blunted in 3 patients.

Abstract | Full Text PDF

5-HT2A reseptör genindeki T102C polimorfizmi muhtemelen bu reseptörün fonksiyonlarýný etkilemektedir. Pediatrik inmede 5-HT2A reseptör genindeki T102C varyantý ile ilgili mevcut bilgi olmadýðý için çalýþmamýzda; bu polimorfizm ile pediatrik inme arasýnda iliþki olup olmadýðýný araþtýrmayý amaçladýk. Serebral inme öyküsü olan 111 çocuk (10 ay-18 yaþ) ve 79 saðlýklý kontrol çalýþmaya dâhil edildi. 5-HT2A reseptör genindeki T102C deðiþimi PCR tekniði ile çalýþýldý. Sonuç olarak; bu polimorfizm ne tek baþýna ne de diðer altta yatan protrombotik faktörlerle birlikte deðerlendirildiðinde pediatrik inme ile iliþkili bulunmadý, ne var ki bu bilgi daha sonraki çalýþmalarla da aydýnlatýlmalýdýr.

Platelet-dependent thromboembolism is an underlying mechanism in the pathogenesis of stroke. 5-HT2A receptor gene is expressed in human platelet, coronary artery (blood vessels) and brain. A polymorphism T102C at the 5-HT2A receptor gene was found that may possibly affect the 5-HT2A receptor function. As there is no existing data on T102C variant of 5-HT2A receptor gene in pediatric stroke, we aimed to study in this case-control study whether there is a association between this polymorphism and pediatric stroke. 111 patients (10 months-18 years old) with cerebral infarct and 79 healthy control was included to our study. Polymerase chain reaction (PCR) of the T102C alteration at the 5-HT 2A receptor gene was performed. Our data revealed that, 5-HT (2A) receptor T102C polymo phism was not associated with pediatric stroke in our population either alone or in combination with underlying pro thrombotic factors. However, this needs to be clarified with further studies.

Abstract | Full Text PDF

Fibrinogen, one of the most hemorheologically active plasma proteins, is associated with several cardiovascular risk factors, and the plasma concentration can alter dramatically during acute phase response and in a wide variety of clinical conditions. We have assessed fibrinogen levels in some known cardiovascular disorders, during usage of contraceptive pills, acute phase conditions and pregnancy. Our results from patients with various disease conditions indicate that fibrinogen levels are in the pathological range and are significantly higher than in healthy controls (p<0.001). It is concluded that although Africans have low predisposition to thrombosis, they may well be pre-disposed to abnormal fibrin formation which could lead to various thromboembolic complications.

Abstract | Full Text PDF

In vitro koþullarda fludarabin içeren kombinasyonlarýn lösemik blastlar üzerinde ve fludarabin ya da kladribinin imatinib mesilat ile kombinasyonlarýnýn KML CFU-GM hücrelerine karþý aditif etkinliðe sahip olduklarý gösterilmiþtir. Bu gözlemlere dayanarak biz de fludarabin ve imatinib mesilat kombinasyonunun KML blastik faz hücre serileri K562 ve Meg-01 üzerine olan etkinliðini araþtýrmayý planladýk. Proliferasyon ve inhibisyon göstergesi olarak XTT testini kullandýk. Elde edilen verilere göre, her ilacýn beþ farklý etkin konsantrasyonu 25 farklý kombinasyon halinde test edildi. Kombinasyon çalýþmalarýnýn sonuçlarý izobologram ile analiz edildi. Ýmatinib mesilat ve fludarabinin kombinasyonunun K562 ve Meg-01 hücre serileri için IC20 kombinasyon indeksi deðerleri sýrasý ile sinerjistik ve güçlü sinerjistik, IC50 ve IC75 deðerlerinde de güçlü sinerjistik ve sinerjistik etkinliði göstermekte idi. Bu sonuçlar KML blastik fazdaki hastalar için imatinib mesilat ile kombine edilen fludarabin bazlý rejimlerin kullanýlabileceðini göstermektedir.

Fludarabine-containing combinations have additive cell killing against leukemic blasts in vitro. It has also been shown that imatinib mesylate combined with fludarabine or cladribine had an additive effect on CML CFU-GM cells. In this regard, we aimed to investigate the effect of fludarabine-imatinib mesylate combination against CML blastic phase cell lines K562 and Meg-01. XTT test was performed for proliferation and inhibition assay. According to obtained data, five different effective concentrations of each drug in 25 different combinations were tested. Results of the combination studies were analyzed with isobologram. At IC20, imatinib mesylate and fludarabine combination showed synergism and strong synergism in K562 and Meg-01 cells, respectively. At IC50 and IC75, combination indexes (CI) indicated strong synergism and synergism. Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate.

Abstract | Full Text PDF

Lösemiler kendileri direk invazyon yoluyla ya da hematolojik parametrelerde oluþturduklarý anomalilerle nörolojik bozukluklara yol açabildikleri gibi, lösemi tedavisinde yer alan santral sinir sistemi (SSS) profilaksi rejimleri de nörotoksisite oluþturabilmektedir. Intratekal kemoterapi, radyoterapi ve yüksek doz Ara-C ya da metotreksat içeren sistemik kemoterapiler SSS tutulumu proflaksisi veya tedavisinde etkindirler. Ýntratekal (IT) metotreksat tedavisi sonrasý menenjial irritasyon bulgularýna sýk rastlanmakla beraber nadir olarak paralizi veya ensefalopati vakalarý da bildirilmiþtir. ALL-L1 tanýsý konan 24 yaþýnda bir bayan hastaya Hyper-CVAD (yüksek doz Ara- C ve yüksek doz metotreksat) kemoterapi rejimi uygulanmaya baþlandý. Hyper- CVAD kemoterapi rejiminin ikinci kürü sýrasýnda, IT metotreksattan iki gün sonra hastamýzda nörojenik mesane ve konstipasyon geliþti. Cauda Equina sendromu tanýsý konan hastanýn lumbo-sakral MRI görüntülemesinde Kauda Equina bölgesinde opaklaþma olduðu görüldü. Bu sýrada yapýlan lomber ponksiyon ve serebrospinal sývý incelemesi ile bu opaklaþmanýn lösemik tutuluma baðlý olmadýðý kanýtlandý. Literatürde spinal anesteziye sekonder geliþen Cauda Equina sendromu bildirilmiþ olsa da, vakamýz intratekal metotreksat sonrasý görülen ilk Cauda Equina sendromu vakasýdýr.

The leukemias may cause neurologic dysfunction through either direct invasion of the nervous system or indirectly through cytopenias, or it may occur as a result of the necessarily vigorous treatment programs for leukemia. We report here a 24-year-old acute lymphoblastic leukemia patient who in her second cycle of hyper-CVAD chem therapy regimen (high-dose Ara-C and high-dose methotrexate) received intrathecal methotrexate and two days afterwards was diagnosed as having Cauda Equina syndrome (CES). A lumbo-sacral MRI imaging with gadolinium was performed and there was a remarkable enhancement in the Cauda Equina region, suggesting either leukemic involvement or a type of neurologic complication associated with intrathecal methotrexate treatment. To rule out leukemic involvement, a lumbar puncture was performed and the CSF was free of leukemic cells. There are cases of CES developing after spinal anesthesia reported in the literature, but this is the first report of CES due to intrathecal methotrexate.

Abstract | Full Text PDF

Daha öncesinde saðlýklý olan 12 yaþýndaki kýz hasta Pediatrik Yoðun Bakým Ünitesine aðýr pulmoner kanama ile yatýrýldý. Öyküsünde 2 haftadýr devam eden yüksek ateþ, halsizlik, boðaz aðrýsý, kas aðrýlarý ve yaygýn döküntüsü olduðu tanýmlanmaktaydý. Fizik bakýda karaciðer ve dalak büyüklüðü izlendi. Laboratuvar tetkiklerinde yüksek ferritin, trigliserid ve LDH deðerleri ile birlikte düþük fibrinojen düzeylerine eþlik eden pansitopeni saptandý. Kemik iliði aspirasyonunda belirrgin hemofagositoz izlendi. Kemik iliði biyopsisi ile hemofagositoz doðrulandý ve yoðun miyelofibrosis saptandý. Serolojik olarak EBV Viral kapsid antijene karþý IgM antikorlarýn pozitifliði gösterildi. Hasta destek tedaviye ve IVIG uygulamalarýna yanýt vermeyince 10 gün süreyle HLH 2004 tedavi protokolüne uygun olarak kemoterapi aldý. Hasta uzun süreli mekanik ventilasyon izlemi sonrasýnda sepsis ve pulmoner kanama tablosunda kaybedildi. Özellikle EBV iliþkili HLH’de nadiren bildirilen ileri derecede kemik iliði myelofibrosisi bu hastadaki ölümcül gidiþe katkýda bulunmuþtur.

A previously healthy 12-year-old girl was admitted to the intensive care unit with severe pulmonary bleeding. Her history revealed that she had suffered from high fever, fatigue, sore throat, myalgia and generalized rash for two weeks. Physical examination revealed hepatosplenomegaly. Laboratory investigation showed pancytopenia associated with unusual high levels of serum ferritin, triglyceride and lactate dehydrogenase (LDH) and low fibrinogen levels. Apparent hemophagocytosis was seen in bone marrow aspiration. Bone marrow biopsy revealed myelofibrosis, and confirmed hemophagocytosis. IgM for Epstein-Barr virus (EBV) viral capsid antigen was found to be positive. She received chemotherapy for 10 days according to hemophagocytic lymphohistiocytosis (HLH)-2004 treatment protocol, since the symptoms persisted despite supportive therapy and intravenous immunoglobulin (IVIG) administration. However, the clinical status and laboratory findings did not respond to treatment and she died from severe pulmonary bleeding associated with prolonged ventilator support and sepsis. Intense myelofibrosis, which is reported rarely, particularly in patients with EBV-related HLH, contributed to this fatal prognosis.

Abstract | Full Text PDF

Abstract | Full Text PDF

Abstract | Full Text PDF