Dameshek’e göre gerçek polistemi (polistemia vera: PV) eþ zamanlý eritrositoz, lökositoz ve trombositozun olduðu, yayýlma özelliði göstermeyen, tüm kemik iliðini ilgilendiren miyeloproliferatif bir hastalýktýr. Olasý kalýtsal veya iletilebilme eðilimi olabilir, ancak gerçek ailevi polistemi nadirdir. Etyolojiye yönelik olarak Dameshek 1950’de iki çok tartýþmalý olasýlýk ileri sürmüþtür: bilinmeyen faktör veya faktörlerce kemik iliðinin aþýrý uyarýlmasý ve normal baskýlayýcý faktör veya faktörlerin eksikliði veya olmamasý. Dameshek’in hipotezi 2005 yýlýnda Fransa’da Vainchecker tarafýndan 3 klasik miyeloproliferatif neoplazinin fenotipinin nedeni olarak edinsel JAK2V617F mutasyonunun keþfi ile ispatlandý: esansiyel trombositemi, PV ve miyelofibroz. JAK2V617F mutasyonu Janus kinaz 2 (JAK2)’nin parçasý JH1 kinaz üzerinde yer alan JH2 yalancý kinazýn baskýlayýcý aktivitesinin kaybýna neden olmaktadýr. Bu durum JAK2’nin normal JH1 kinaz aktivitesinin artýþýna neden olarak mutasyona uðramýþ hematopoetik kök hücrelerini trombopoetin, eritropoetin, insulin-benzeri büyüme faktörü-1, kök hücre faktörü ve granülosit koloni uyarýcý faktor gibi hematopoetik büyüme faktörlerine karþý ileri derecede hassaslaþtýrmak suretiyle her üç seride miyeloproliferasyona neden olmaktadýr. Sonuç olarak, Dameshek tarafýndan gözlemlenen durum PV’da kemik iliðinde kan üretiminini sýnýrlayan tüm kontrol basamaklarýnýn JAK2V617F mutasyonu ile ortadan kaldýrýldýðýdýr.
Dameshek PV hastalarýný özünde normal olarak deðerlendirdiðinden tedavinin mümkün olduðunca fizyolojik olmasý gerekmekteydi. Bu nedenle, sistematik flebotomi/demir eksikliði tedavi metodu önerildi; radyoaktif fosfor kullanýmý dirençli ve major trombozu olan hastalara saklandý. Hasta yeterince uzun yaþar ve tromboz etkisi ya da diðer komplikasyonlara baðlý kaybedilmezse, ilik giderek azalan aktivite belirtileri gösterecektir. Kan yaymasýnda çekirdekli eritrositler, artmýþ polikromatofili, deðiþik tiplerde olgunlaþmamýþ granülositler izlenir. Eritropoetik dokunun gittikçe azalmasýyla, miyelofibroz daha çok organize bir fibröz doku kitlesine dönüþür. Aþýrý büyüyen ve bazý olgularda tüm karýn boþluðunu dolduran dalakta belirgin ekstramedüller hematopoez vardýr. Büyümüþ dalak, büyük ölçüde dalaðýn primer miyeloid metaplazisi alanýnda yerleþen metastatik kemik iliðinden meydana gelir.

According to Dameshek, true polycythemia (polycythemia vera: PV) is a chronic myeloproliferative disorder of the total bone marrow without any evidence of invasiveness, in which erythrocytosis, leukocytosis, and thrombocytosis are all simultaneously present. A possible hereditary or transmitted tendency may be present, but actual familial polycythemia is rare. As to the etiology, Dameshek proposed 2 highly speculative possibilities in 1950: the presence of excessive bone marrow stimulation by an unknown factor or factors, and a lack or a diminution in the normal inhibitory factor or factors. Dameshek’s hypothesis was confirmed in 2005 by Vainchenker in France by the discovery of the acquired JAK2V617F mutation as the cause of 3 phenotypes of classical myeloproliferative neoplasms: essential thrombocythemia, PV, and myelofibrosis. The JAK2V617F mutation induces a loss of inhibitory activity of the JH2 pseudokinase part on the JH1 kinase part of Janus kinase 2 (JAK2). This leads to enhanced activity of the normal JH1 kinase activity of JAK2, which makes the mutated hematopoietic stem cells hypersensitive to the hematopoietic growth factors thrombopoietin, erythropoietin, insulin-like growth factor-1, stem cell factor, and granulocyte colony-stimulating factor, resulting in trilinear myeloproliferation. In retrospect, the situation observed by Dameshek where all “stops” to blood production in the bone marrow are pulled in PV is caused by the JAK2V617F mutation.
Dameshek considered PV patients as fundamentally normal and therefore the treatment should be as physiologic as possible. For this reason, a systematic phlebotomy/iron deficiency method of treatment was recommended; the use of radioactive phosphorus is reserved for refractory cases and cases of major thrombosis. If the patient lives long enough and does not succumb to the effects of thrombosis or other complications, the marrow will gradually show signs of diminished activity. The blood smear shows nucleated red cells, increased polychromatophilia, and immature granulocytes of various types. With increasing reduction of erythropoietic tissue, myelofibrosis becomes more of an organized mass of fibrous tissue. There is prominent extramedullary hematopoiesis in the spleen, which becomes extraordinarily large and in some cases occupies almost the entire abdominal cavity. The enlarged spleen is made up largely of metaplastic marrow tissue in primary myeloid metaplasia of the spleen.

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AMAÇ: 5-Azasitidin miyelodisplastik sendrom tedavisinde kullanýlan hipometile edici bir ajandýr. Bu histon deðiþtiricisi, kök hücrelerin diferansiyasyon yeteneði üzerinde yaygýn olarak etkilidir ve bu konuda seçici olmayan bir rol oynamaktadýr. Üç farklý dozda 5-azasitidine maruz kaldýktan sonra, kemik iliði mezenkimal kök hücrelerinin kardiyomiyosit ve miyosit benzeri hücrelere diferansiyasyon yeteneði irdelendi ve karþýlaþtýrýldý. Bu çalýþmanýn amacý, 5-azasitidinin insan mezenkimal kök hücrelerinin (MKH) kardiyomiyosit ve miyosite diferansiyasyonunu saðlamak için gerekli olan etkin dozunun tespit edilmesidir.
YÖNTEMLER: Ýnsan kemik iliði aspirasyonlarý saðlýklý donörlerden yapýldý. MSCler osteoblast ve adipozit farklýlaþmasý için kültüre edildi. Osteojenik veya adipojenik özellikler immunositokimyasal boyama ile incelendi. BMMSCler tripsinize edilerek tek hücre süspansiyonu elde edildi ve akým sitometri için hazýrlandý. MSClere 5, 10 veya 15 μM 5-azacytidine 24 saat uygulandý, daha sonra 3 hafta kültüre edildi. Total RNA 5-azacytidine uygulanan ve uygulanmayan hücrelerden elde edildi. Troponin T ve GATA4 antikorlarý kardiyojenik belirteçler, myojenin ve MyoD antikorlarý myosit belirteçleri olarak kullanýldý.
BULGULAR: 5-Azasitidinin her 3 dozuna da maruz kalmýþ MKH’lerin morfoloji ve büyüme hýzlarý, kontrol MKH’lerin morfoloji ve büyüme hýzlarý ile benzerdi. Ýmmünfloresans yöntemi ile kalbe özgül belirteçler olan GATA4 ve troponin T ile çizgili kasa özgül belirteçler olan MyoD ve miyojenin sunumlarýnýn incelenmesi sonucunda, 15 μM 5-azasitidine maruz kalan hücrelerde bu belirteçlerin kuvvetli pozitif olduðu görüldü. Gerçek zamanlý polimeraz zincir reaksiyonu sonuçlarý incelendi; 15 μM 5-azasitidine maruz kalan MKH’lerde, daha düþük doz 5-azasitidin alan veya 5-azasitidin uygulanmayan MKH’lere göre kalp ve çizgili kasa özgül mRNA’larýn daha yüksek oranda sunum düzeyleri olduðu tespit edildi.
SONUÇ: 5-Azasitidine maruz býrakýlan MKH’lerin kardiyomiyosit ve miyositlere diferansiye olma yeteneði olduðu ve en uygun dozun 15 μM 5-azasitidin olabileceði gösterildi. MKH’lerin özgül hücre tiplerine diferansiyasyonunu incelemek için bunu etkileyebilecek diðer faktörlerin de irdelenmesi gerekmektedir.

OBJECTIVE: 5-Azacytidine is a hypomethylating agent that is used for the treatment of myelodysplastic syndrome. This histone modifier is widely employed and plays a nonspecific role in influencing the differentiation capability of stem cells. The ability of bone marrow mesenchymal stem cells to differentiate into cardiomyocyte- and myocyte-like cells after exposure to 3 different doses of 5-azacytidine has been evaluated and compared. The aim of the study was to optimize the effective dose of 5-azacytidine for promoting the cardiomyocyte and myocyte differentiation capabilities of human mesenchymal stem cells (MSCs).
METHODS: Human bone marrow aspirations were collected from healthy donors. MSCs were used for the study of mesodermal differentiation. MSCs were cultured to promote osteoblast differentiation and adipocyte differentiation. The evaluation of osteogenic or adipogenic properties was then performed through immunocytochemical staining. BMMSCs were trypsinized into single-cell suspensions and then prepared for flow cytometric analysis. The MSCs were treated with 5, 10, or 15 μM 5-azacytidine for 24 h and then cultured for 3 weeks. Total RNA was extracted from untreated and 5-azacytidine–treated cells. Troponin T and GATA4 antibodies were used as cardiogenic markers, whereas myogenin and MyoD antibodies were used as myocyte markers.
RESULTS: The morphology and growth rate of MSCs that were treated with any of the 3 doses of 5-azacytidine were similar to the morphology and growth rate of control MSCs. An immunofl uorescence analysis examining the expression of the cardiac-specifi c markers GATA4 and troponin T and the skeletal muscle-specifi c markers MyoD and myogenin revealed that cells treated with 15 μM 5-azacytidine were strongly positive for these markers. Real-time RT-PCR results were examined; these amplifi cations indicated that there were higher expression levels of cardiac- and skeletal muscle-specifi c mRNAs in MSCs treated with 15 μm 5-azacytidine than in MSCs that had either been treated with lower doses of 5-azacytidine or left untreated.
CONCLUSION: MSCs treated with 5-azacytidine demonstrated the capacity to differentiate into both cardiomyocytes and skeletal myocytes, and 15 μM 5-azacytidine could be the optimal dose of this drug. Other promoting factors should be examined to investigate the possibility of promoting the differentiation of MSCs into specific cell types.

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AMAÇ: Çalýþmamýzýn amacý, hematolojik malignitelerde gözlenen genetik deðiþimlerin tespitinde, yeni bir BAC tabanlý array yaklaþýmý olan HTFA metodunun etkinliðini gözlemlemektir.
YÖNTEMLER: Taný, tedavi ve /veya takip sürecinde olan toplam 77 (n=19 MDS, n=17 ALL, n=9 KML, n=32 AML) hematolojik maligniteli olgudan alýnan kemik iliði aspirasyon ve periferik kan materyallerine HTFA metodu uygulandý.
BULGULAR: Olgularýmýzda hem sayýsal hem de yapýsal kromozomal anomaliler tespit edildi. Anomali görülme oraný tanýya göre farklýlýk göstermektedir. ALL olgularýnýn %88’inde, AML olgularýnýn %25’inde ve MDS olgularýnýn ise %31’inde aberasyon gözlenmiþ olup, KML olgularýnda ise aberasyon saptanmamýþtýr.
SONUÇ: HTFA yönteminin, diðer yöntemlerle birlikte kullanýldýðýnda, hematolojik malignitelerin rutin taný þemalarýnda yer alabileceðini göstermektedir.

OBJECTIVE: The aim of this study was to determine the efficiency of the high throughput FISH analysis (HTFA) method for detecting genetic alterations in hematological malignancies, which is a new bacterial artificial chromosome array-based approach.
METHODS: We performed a HTFA study of bone marrow aspiration and peripheral blood samples of 77 cases (n=19 myelodysplastic syndrome, n=17 acute lymphoblastic leukemia, n=9 chronic myeloid leukemia, n=32 acute myeloid leukemia) with hematological malignancies during the periods of initial diagnosis, treatment, and/or follow-up.
RESULTS: Both numerical and structural abnormalities were detected by HTFA. We observed aberrations in 88% of our acute lymphoblastic leukemia patients, 25% of acute myeloid leukemia patients, and 31% of myelodysplastic syndrome patients. In chronic myeloid leukemia cases, aberration was not detected by HTFA.
CONCLUSION: Our results showed that HTFA, combined with other methods, will gradually take a place in the routine diagnosis of hematologic malignancies.

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AMAÇ: Nükleofosmin 1 (NPM1) genine ait olan ve ürünü hücrealtý düzeyde deðiþtiren somatik mutasyonlar, akut miyeloid lösemi (AML) hastalarýnda en sýk tespit edilen mutasyonlardýr. Bu çalýþmada AML hastalarýnda NPM1 gen mutasyonlarýnýn prevalansýnýn ve prognostik öneminin deðerlendirilmesi amaçlanmýþtýr.
YÖNTEMLER: Elli beþ AML hastasýnda NPM1 gen taramasý için polimeraz zincir reaksiyonu ve tek-iplik konformasyon polimorfizmi kullanýldý.
BULGULAR: Elli beþ hastanýn 12’sinde (%21,8) NPM1 mutasyonlarý bulundu ve mutasyon varlýðýnýn yüksek lökosit sayýsý, kemik iliði blast oraný (sýrasýyla, p=0,03; p=0,02) ve M5 alt tipi (p<0,001) ile anlamlý iliþkisi olduðu tespit edildi. NPM1 mutasyonu olan hastalar, daha yüksek oranda tam remisyon (p=0,003), daha düþük mortalite eðilimi, nüks ve dirençli hastalýk riski (sýrasýyla, p=0,28, p=0,45, p=0,08) taþýmaktaydý. Saðkalým analizinde, hastalýksýz saðkalým (18,635±1,229 vs. 11,041±1,250 ay, p=0,044) ve genel saðkalým (ortalama 19,810±1,624 vs. 12,063±1,244 ay, p=0,041), NPM1 mutasyonu taþýyanlarda taþýmayanlara göre anlamlý olarak daha uzun bulundu. Çok-deðiþkenli analizde, NPM1 mutasyonunun hastalýksýz saðkalým (HR=0,066, p=0,001) ve genel saðkalým (HR=0,125, p=0,002) için anlamlý baðýmsýz öngörücü olduðu görüldü.
SONUÇ: NPM1 mutasyonu, Mýsýrlý hastalarda iyi gidiþ ile iliþkili olan bir prognostik faktördür. NPM1 mutasyonu kullanýlarak heterojen bir hastalýk olan AML’nin prognoz açýsýndan farklý alt gruplara ayrýlmasý mümkün olabileceðinden bu sonuç önemli bulunmuþtur.

OBJECTIVE: Somatic mutations of the nucleophosmin gene (NPM1), which alter the subcellular localization of the product, are the most frequent mutations in patients with acute myeloid leukemia. The aim of the study was to assess the prevalence and prognostic impact of NPM1 gene mutations in adult AML patients.
METHODS: Polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) were used to screen 55 AML patients for mutations of NPM1 gene.
RESULTS: NPM1 mutations were found in 12 (21.8%) of 55 patients, significantly associated with higher total leukocytie count, marrow blast percentage (p=0.03 and p=0.02, respectively), and M5 subtype (p<0.001). Patients with NPM1 mutations had significantly higher complete remission rates (p=0.003) and a trend to lower rates of mortality, relapse and refractory disease (p=0.28, p=0.45 and p=0.08, respectively). Survival analysis showed significantly longer disease-free survival (mean 18.635±1.229 versus 11.041±1.250 months, p=0.044) and overall survival (mean 19.810±1.624 versus 12.063±1.244 months, p=0.041) in patients with NPM1 mutations compared with those without. Multivariate analyses confirmed NPM1 mutation as a significant independent predictor for disease-free survival (HR=0.066, p=0.001) and overall survival (HR=0.125, p=0.002).
CONCLUSION: NPM1 mutation is a prognostic factor for a favorable outcome in Egyptian population. This finding is of major clinical importance since it strongly suggests that NPM1 mutations may allow one to divide the heterogeneous patient group of AML into prognostically different subgroups.

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AMAÇ: Akut miyeloid lösemi (AML) patofizyolojisinde anjiyogenezinönemli rol oynadýðý ileri sürülmektedir. Anjiyogenezdeki anahtar düzenleyicilerden biri damar endotel büyüme faktörü- vascular endothelial growth factor (VEGF)- dür. VEGF ailesi içinde, VEGF-A ve VEGF-C’nin AML hücreleri tarafýndan eksprese edildiði ve lösemik hücrenin proliferasyonu, yaþamý ve kemoterapiye direncine aracý olduðu gözlenmiþtir. Buna raðmen mevcut bilgiler, artmýþ VEGF düzeylerinin veya proanjiyogenik bir fenotipin erken tümör geliþimi ve progresyonunu tetiklemekten ziyade engelleyebildiðini göstermiþtir. VEGF-A ve VEGF-C düzeylerinin AML patogenezindeki yeri tam olarak açýklanamadýðýndan, bu çalýþmanýn amacý Ýranlý AML hastalarýnýn periferik kan mononükleer hücrelerinde sözügeçen anjiyogenez düzenleyicilerinin gen ekspresyonlarýný ve prognostik deðerini incelemektir.
YÖNTEMLER: Yirmi yedi yeni taný AML hastasý ile 28 saðlýklý köntrolün periferik kan mononükleer hücrelerinde kantitatif real-time PCR ile VEGF-A ve VEGF-C’nin mRNA ekspresyonu araþtýrdýk.
BULGULAR: AML hastalarýndaki VEGF-C mRNA ekspresyonu saðlýklý kontrollere göre belirgin olarak düþüktü (p<0.001). Buna karþýlýk VEGF-A mRNA ekspresyonunda kontrol grubuna göre anlamlý bir azalma yoktu (p=0.861). VEGF-A ve VEGF-C ekspresyonunun klinik sonucu ön görme kapasitesi yoktur.
SONUÇ: Bulgularýmýz AML’nin azalmýþ VEGF-C mRNA ekspresyonu ile iliþkili olduðunu gösterdi. Buna raðmen ekspresyon düzeyleri bizim çalýþmamýzda klinik sonucu etkilemedi. Hem VEGF baþka sitokinlerden hem de anjiyogenez VEGF-C veya VEGF-A’dan baþka sitokinlerden etkileniyor gibi görünmektedir. Sonuç olarak, bulgularýmýz AML patogenezinde rolü olabilecek diðer anjiyojenik faktör ve sitokinlerin araþtýrýlmasýna yeni bir bakýþ açýsý saðlayarak yardýmcý olacaktýr.

OBJECTIVE: The crucial role of angiogenesis in the pathophysiology of acute myeloid leukemia (AML) has been proposed. One of the key regulators of angiogenesis is the vascular endothelial growth factor (VEGF). Among the VEGF family, it has been observed that VEGF-A and VEGF-C are expressed by AML cells and mediate leukemic cell proliferation, survival, and resistance to chemotherapy. Emerging evidence, however, suggests that elevated levels of VEGF or a proangiogenic phenotype may impede, rather than promote, early tumor development and progression. As the significance of VEGF-A and VEGF-C levels in the pathogenesis of AML has not been clarified well, the aim of this study is to evaluate gene expression of these angiogenesis promoters and its possible prognostic value in peripheral blood mononuclear cells of Iranian patients with AML.
METHODS: We investigated the mRNA expression of VEGF-A and VEGF-C in peripheral blood mononuclear cells of 27 patients with newly diagnosed AML and 28 healthy controls by quantitative real-time PCR.
RESULTS: Expression of VEGF-C mRNA was significantly lower in AML patients than in healthy controls (p<0.001). However, there was no significant decrement in expression of VEGF-A mRNA of AML patients compared to the control group (p=0.861). VEGF-A and VEGF-C expression were not able to predict clinical outcome.
CONCLUSION: Our data showed that AML is associated with a decreased expression of VEGF-C mRNA. However, expression levels did not influence the clinical outcome in our study. It seems that angiogenesis is affected by different cytokines other than VEGF-C or VEGF-A, and VEGF is also affected by different cytokines. Taken together, these findings help to provide new insights into the investigation of other angiogenic factors and cytokines that may play roles in the pathogenesis of AML.

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AMAÇ: Bu çalýþmada, demir eksikliði anemisi tedavisinde ferröz sulfat verildiðinde çinko sülfatýn büyüme ve serum demir deðiþkenleri üzerine etkinliðini karþýlaþtýrmayý amaçladýk.
YÖNTEMLER: Hastalar (n=79) rastgele iki gruba ayrýldý. Bir gruba (n=40) 4 mg/kg/gün’den oral yolla ferröz sülfat verildi. Diðer gruba ise (n=39) ferröz sülfata ek olarak 5 mg/gün’den çinko sülfat verildi.
BULGULAR: Baþlangýç deðerleri ile karþýlaþtýrýldýðýnda tedavinin 3. ayýnda her iki grupta ortalama boy, vücut aðýrlýðý ve baþ çevresi açýsýndan istatistiksel olarak anlamlý bir artýþ tespit edildi. Ancak, iki grup arasýnda ortalama boy, vücut aðýrlýðý ve baþ çevresinde tedavinin baþlangýç (sýrasýyla 83,43±11,3 cm ve 84,62±12,77 cm; 12,36±3,08 kg ve 12,72±3,87 kg; 47,33±2,15 cm ve 47,26±2,73 cm), 1. ay (sýrasýyla 84.82±10,97 ve 85,97±12,28; 12,78±3,09 ve 13,09±3,87; 47,76±2,10 ve 47,61±2,67) ve 3. aylarý (sýrasýyla 86,4±11,12 ve 87,69±12,13; 12,9±3,06 ve 13,35±3,81; 48,22±1,89 ve 48,07±2,45) karþýlaþtýrýldýðýnda istatistiksel bir farklýlýk yoktu. Ortalama hematolojik parametrelerde de iki grup arasýnda baþlangýç, 1. ay ve 3. ay deðerleri karþýlaþtýrýldýðýnda istatistiksel fark görülmedi (sýrasýyla grup 1 ortalama Hb: 8,78±1,12 g/dL; 11,27±1,09 g/dL; 12,05±1,0 g/dL, grup 2 ortalama Hb: 9,10±1,07 g/dL; 11,12±0,85 g/dL; 11,80±0,79 g/dL). Baþlangýç ortalama ferritin ve çinko deðerleri gruplar arasýnda istatistiksel olarak farklý deðildi (ortalama ferritin: 4.96±4.03 μg/dL ve 4,52±2,94 μg/dL, ortalama çinko: 88,64±15,35 ng/mL ve 86,84±17,34 ng/mL). Ortalama ferritin ve çinko düzeyleri 3. ayda istatistiksel olarak anlamlý þekilde yükseldi (ortalama ferritin: 15,91±9,57 μg/dL ve 15,25±10,47 μg/dL; ortalama çinko: 88,02±15,10 ng/mL ve 95,25±16,55 ng/mL).
SONUÇ: Çalýþmamýzda DEA tedavisinde çinko verilmesinin pozitif veya negatif bir etkisi gösterilemedi. Bu yüzden, DEA tedavisinde demire ek olarak çinko farklý zamanlarda, eþlik eden çinko eksikliði varsa verilmelidir.

OBJECTIVE: In this study, we aimed to compare the effect(s) of zinc sulphate on growth and serum iron variables when it is given with ferrous sulphate in iron deficiency anemia (IDA).
METHODS: Patients (n=79) were randomly divided into two groups. In one group (n=40) 4 mg/kg/d ferrous sulfate was given orally. In the other group (n=39), in addition to ferrous sulfate, 5 mg/d oral zinc sulfate was given.
RESULTS: Compared to the initial values statistically significant increase in mean height, weight, and head circumference has been observed in both groups after 3 months. However, there was no statistical difference between two groups concerning mean height, weight, and head circumference at the beginning (83.43±11.3 cm vs 84.62±12.77 cm; 12.36±3.08 kg vs 12.72±3.87 kg; 47.33±2.15 cm vs 47.26±2.73 cm, respectively), at the first month, (84.82±10.97 vs 85.97±12.28; 12.78±3.09 vs 13.09±3.87; 47.76±2.10 vs 47.61±2.67, respectively), and at the third month, (86.4±11.12 vs 87.69±12.13; 12.9±3.06 vs 13.35±3.81; 48.22±1.89 vs 48.07±2.45, respectively). There were no statistical differences between mean hematological parameters of the groups at the beginning, at the first month, and at the third month, either (mean hb of Group 1: 8.78±1.12 g/dL; 11.27±1.09 g/ dL; 12.05±1.00 g/dL respectively and of Group 2: 9.10±1.07 g/dL; 11.12±0.85 g/dL; 11.80±0.79 g/dL, respectively). Mean ferritin and zinc values of the groups were statistically insignificant at the beginning (Mean ferritin: 4.96±4.03 μg/dL vs 4.52±2.94 μg/dL, zinc: 88.64±15.35 ng/mL vs 86.84±17.34 ng/mL). Their increase was statistically significant at the third month (mean ferritin: 15.91±9.57 μg/dL vs 15.25±10.47 μg/dL; zinc: 88.02±15.10 ng/mL vs 95.25±16.55 ng/mL).
CONCLUSION: In our study neither positive nor negative effect of zinc administration on IDA treatment was demonstrated. Therefore, in the treatment of IDA zinc together with iron should be used at different times if there is coexistent zinc deficiency.

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AMAÇ: Bu çalýþmanýn amacý, DEA tanýsýnda retikülosit hemoglobin içeriðinin (CHr) klinik önemini belirlemek ve diðer konvansiyonel demir parametreleri ile karþýlaþtýrmaktýr.
YÖNTEMLER: Çalýþmaya demir eksikliði (serum hemoglobin >120 g/L ve serum ferritin <20 ng/mL) olan 18 kadýn hasta ve demir eksikliði anemisi (serum hemoglobin <120 g/L ve serum ferritin <20 ng/mL) olan 32 kadýn hasta dahil edildi.
BULGULAR: Demir eksikliði anemisi olan hastalarda retikülosit hemoglobin içeriði 24,95±3,92 pg, demir eksikliði olan hastalarda ise 29,93±2,96 pg idi. CHr; hemoglobin, MCV, MCH, MCHC, serum demiri ve transferrin saturasyonu ile anlamlý pozitif korelasyon; transferrin ve total demir baðlama kapasitesi ile anlamlý negatif korelasyon gösterdi. DEA tanýsý için CHr cut-off deðeri 29 pg olarak saptandý.
SONUÇ: Bizim verilerimiz, CHr’nin DEA tanýsýnda güvenle kullanýlabilecek faydalý bir parametre olduðunu ve 29 pg olan CHr cut-off deðerinin demir eksikliði anemisini öngördüðünü göstermektedir.

OBJECTIVE: The aim of this study was to evaluate the clinical significance of reticulocyte hemoglobin content (CHr) in the diagnosis of iron deficiency anemia (IDA) and to compare it with other conventional iron parameters.
METHODS: A total of 32 female patients with IDA (serum hemoglobin <120 g/L and serum ferritin <20 ng/mL) and 18 female patients with iron deficiency (serum hemoglobin > 120 g/L and serum ferritin <20 ng/mL) were enrolled.
RESULTS: CHr was 24.95±3.92 pg in female patients with IDA and 29.93±2.96 pg in female patients with iron deficiency. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, and transferrin saturation and a significant negative correlation with transferrin and total iron-binding capacity. The cut-off value of CHr for detecting IDA was 29 pg.
CONCLUSION: Our data demonstrate that CHr is a useful parameter that can be confidently used in the diagnosis of IDA, and a CHr cut-off value of 29 pg predicts IDA.

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Amaç: This article has been withdrawn due to the fact that it is published in three different journals.
Gereç ve Yöntem:
Bulgular:
Sonuç:

Objective: This article has been withdrawn due to the fact that it is published in three different journals.
Materials and Methods:
Results:
Conclusion:

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AMAÇ: Kan baðýþçýlarýnda, Hepatit-B, Hepatit-C ve Human Immunodeficiency enfeksiyonlarýnýn prevelansýný belirlemek.
YÖNTEMLER: Ocak 2004’den aralýk 2011’e kadar, 108598 saðlýklý verici, kan bankamýza baðýþta bulunmuþtur. Taramalar, Axsym System (Abbott Diagnostic, USA) için Microparticle Enzyme Immuno Assay (MEIA) methodu ve 2011 yýlýnda da Architect i2000 (Abbott Diagnostic, USA) için Chemiluminescent Immunoassay (CIA) yöntemi ile yapýlmýþtýr. 2010 yýlýndan itibaren, HIV reaktif vericilerin sonuçlarýna doðrulama testleri uygulanmýþ ve kiþilere geri bildirimde bulunulmuþtur.
BULGULAR: Toplam 108598 baðýþçýnýn 108393’ü (%99,8) replasman baðýþçýsý olup, yaþ ortalamasý 28,92 (17-55) idi. Bunlarýn sadece 164’ü (%0,15) kadýndý. Kan baðýþçýlarý arasýnda 4906 (%4,5) olgu Hepatit-B, C ve Human Immunodeficiency Virus yönünden pozitif bulundu. Bunlarýn biri hariç hepsi erkekti. Baðýþçýlarýn 2068’inde (%1,90) Hbs Ag ve 2832’sinde (%2,61) ise anti-HCV pozitif bulundu. 111 (%0,10) kiþi Human Immunodeficiency Virus yönünden pozitifdi. Birden fazla enfeksiyon varlýðý 103 (%0,09) olguda saptandý. Prevelans, görece genç yaþtakilerde (17-30 yaþ) daha yüksek bulundu. Sadece %16,6 olgu HIV doðrulama testi ile pozitif saptanarak reddedildi.
SONUÇ: Çalýþmamýzda kan baðýþçýlarýndaki Hepatit-B ve C seroprevelansý, komþu ülkelerin çalýþmalarýyla kýyaslandýðýnda yüksek bulunmakla birlikte, Pakistan’dan daha evvel yapýlan çalýþmalardaki sonuçlarla karþýlaþtýrýldýðýnda ise görece düþük saptanmýþtýr. Buna karþýn, HIV prevelansý ve doðrulama testine tabi tutulan HIV pozitif olgu sayýsý ise düþük görünmektedir.

OBJECTIVE: To determine the prevalence of Hepatitis-B, Hepatitis-C and Human Immunodeficiency infections in replacement blood donors.
METHODS: From January 2004 to December 2011, 108,598 apparently healthy donors donated blood at our Blood Bank. Screening was done by Microparticle Enzyme Immuno Assay (MEIA) method on Axsym System (Abbott Diagnostic, USA) and in year 2011 by Chemiluminescent Immunoassay (CIA) method on Architect i2000 (Abbott Diagnostic, USA). From 2010 onward, HIV reactive donors were advised for confirmatory tests and reported back with the results.
RESULTS: Of the 108,598 total donors, 108,393 (99.8%) were replacement donors with a mean age of 28.92 (17-55) years. Of this, only 164 (0.15%) were females. Among the replacement donors, 4,906 (4.5%) were found to be reactive for Hepatitis-B, C and Human Immunodeficiency Virus. All the reactive patients, except one, were males. HbsAg was positive in 2,068 (1.90%) and anti-HCV in 2832 (2.61%) donors, while 111 (0.10%) were positive for Human Immunodeficiency Virus. Co-infectivity was observed in 103 (0.09%) cases. The prevalence appeared to be higher in younger age group (17-30 yrs). Only 16.6% cases should be patients returned with results of the confirmatory tests for HIV and were found positive.
CONCLUSION: Hepatitis-B and C sero-prevalence in our series of replacement donors appears high compared to most studies from neighboring countries and relatively low in comparison to earlier studies from Pakistan. Prevalence of HIV, however, appears low and turn out of HIV positive cases for confirmatory tests is low.

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AMAÇ: Kronik menoraji anemiye ve yaþam kalitesinde bozulmaya neden olur. Bu çalýþmanýn amacý adolesan ve genç kadýnlarda pýhtýlaþma bozukluklarýnýn taranmasýdýr.
YÖNTEMLER: Bu çalýþma çocuk hematoloji hekimleri tarafýndan prospektif olarak yapýldý. Araþtýcý tarafýndan hastayla karþýlýklý yapýlan görüþmede hastalarýn demografik özelliklerini, menoraji dýþýndaki diðer kanama öyküsünü, aile öyküsünü, yoðun menstruasyon kanamasýnýn özelliklerini ve bu durumun yaþam kalitesini etkileme derecesini içeren bir form dolduruldu. Menstruasyondaki kan kaybýnýn yoðunluðunu deðerlendirmek için resimli kanama deðerlendirme çizelgesi kullanýldý. Tüm hastalara jinekologlar tarafýndan pelvik muayene ve ultrasonografi yapýldý. Tam kan sayýmý, periferik yayma, kan grubu, serum transaminazlarý, üre, kreatinin, ferritin, PFA-100, PZ, aPTZ, INR, TT, fibrinojen, VWF: Ag, VWF: RCo, FVIII, trombosit agregasyon testleri yapýldý. Trombosit agregasyon testleri lumiagregometri yöntemiyle çalýþýldý.
BULGULAR: Çalýþmaya 75 hasta ile baþlandý 60 hasta çalýþmayý tamamladý. Ortalama yaþ 20,68±10,34 (10-48) olan hastalarýn %65’i (n=39) 18 yaþýn altýndaydý. Adolesanlarýn %46’sýnda (n=18) menoraji kendiliðinden düzeldi. Hastalarýn %20’sinde (n=12) pýhtýlaþma bozukluðu saptandý. (1 hasta Tip III Von Willebrand hastalýðý, 2 hasta düþük VWF: Ag, 1 hasta olasý Von Willebrand hastalýðý, 3 hasta Bernard-Soulier sendromu, 2 hasta Glanzmann trombastenisi, 2 hasta immun trombositopenik purpura, 1 hasta doðumsal FVII eksikliði).
SONUÇ: Menorajili hastalarda baþlangýçta tam kan sayýmý, periferik yayma, aPTZ, PZ, VWF: Ag, VWF: RCo, FVIII ve fibrinojen düzeyleri bakýlmalýdýr. Burun ve diþeti kanamasý hikayesi varlýðýnda, trombosit fonksiyonlarý lumiagregometrik yöntemle deðerlendirilmelidir. Adolesanlarýn yaklaþýk %50’sinde menoraji hormonal fonksiyon bozukluðuna baðlý ve geçicidir. Detaylý pýhtýlaþma testlerinin yapýlmasý menoraji dýþýnda kanama hikayesi olanlar ve/veya ailevi kanama hikayesi olanlar ve/veya akraba evliliði olan hastalar dýþýnda ertelenmelidir. Tüm menorajili hastalar jinekoloji ve hematoloji hekimleri tarafýndan deðerlendirilmelidir.

OBJECTIVE: Chronic menorrhagia causes anemia and impairment of life quality. In this study the aim was the screening of bleeding disorders in adolescents and young women with menorrhagia.
METHODS: The study was performed prospectively by pediatric hematologists. A form including demographic characteristics of the patients, bleedings other than menorrhagia, familial bleeding history, characteristics of the menorrhagia, and impairment of life quality due to menorrhagia was filled out by the researcher during a face-to-face interview with the patient. A pictorial blood assessment chart was also used for evaluation of blood loss. All patients underwent pelvic ultrasound sonography testing and women also received pelvic examination by gynecologists. Whole blood count, peripheral blood smear, blood group, serum transaminases, urea, creatinine, ferritin, PFA-100, PT, aPTT, INR, TT, fibrinogen, VWF: Ag, VWF: RCo, FVIII, and platelet aggregation assays were performed. Platelet aggregations were studied by lumiaggregometer.
RESULTS: Out of 75 patients enrolled, 60 patients completed the study. The mean age was 20.68±10.34 (range: 10-48) years and
65% (n=39) of the patients were younger than 18 years. In 18 (46%) of the adolescents, menorrhagia subsided spontaneously.
In 20% (n=12) of the patients, a bleeding disorder was detected (1 case of type 3 von Willebrand disease, 2 patients with low
VWF: Ag, 1 case of probable von Willebrand disease, 3 cases of Bernard-Soulier syndrome, 2 cases of Glanzmann thrombasthenia, 2 cases of immune thrombocytopenic purpura, 1 case of congenital factor VII deficiency).
CONCLUSION: In patients with menorrhagia, at least complete blood count, peripheral smear, aPTT, PT, VWF: Ag, VWF: RCo, FVIII, and fibrinogen assays must be performed. When there is history of nose and gum bleeding, platelet function assay by lumiaggregometer must also be performed. In nearly 50% of adolescents, menorrhagia is dysfunctional and transient. Detailed coagulation assays can be postponed in adolescents if bleeding history other than menorrhagia and/or family history of bleeding and/or parental consanguinity is absent. All subjects with menorrhagia must consult with gynecologists and hematologists.

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Esansiyel trombositoz, trombohemorajik komplikasyonlarýn sýk görüldüðü miyeloproliferatif hastalýklardan biridir. Hidroksiürenin bu durum için etkili bir tedavi olduðu kanýtlanmýþtýr. Bununla birlikte, yan etkisiz deðildir. Bu makalede refrakter bacak ülserleri geliþen 3 esansiyel trombositoz hastasýnda hidroksiüre ile baþarýlý þekilde gerçekleþtirilen tedavi sürecini bildiriyoruz. Ayný zamanda, bu toksisitenin mekanizmasýna ýþýk tutacak literatür gözden geçirilmiþtir. Bu önemli komplikasyonun farkýnda olmak, gereksiz invaziv giriþimlerden kaçýnmak için önemlidir.

Essential thrombocythemia is one of the myeloproliferative neoplasms with a plethora of thrombohemorrhagic complications. Hydroxyurea has been proven to be an effective treatment for this condition. However, it is not without side effects. We herein report 3 patients with essential thrombocythemia treated with hydroxyurea who developed refractory leg ulcers, and we outline their successful management. We also review the literature to shed light on the mechanism of this toxicity. Awareness of this important treatment complication is important to avoid the pitfall of futile invasive interventions.

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Miyeloablatif olmayan allojeneik kök hücre nakli (NST) sonrasý derin ven trombozu (DVT) sýklýðý bilinmemektedir. Ek olarak, allojeneik nakil sonrasý DVT geliþiminin nedenleri ile ilgili çok az sayýda çalýþma mevcut olup, bu çalýþmalarda izole bazý etiyolojik faktörler tanýmlanmýþtýr. Merkezimizde NST protokolleri ile tedavi edilen hastalarda DVT geliþme sýklýðý son sekiz yýl içinde %4,1 (73 hastada 3 vaka) olarak bulunmuþ olup, bu hasta grubunda bildirilen ilk rapordur. NST sonrasý DVT geliþimi ile ilgili gözlemimiz, bu hastalarda birden çok risk faktörünün bir arada bulunduðudur. Burada, bu hasta grubunda DVT geliþen üç vaka sunulmuþ ve ilgili literatür gözden geçirilmiþtir.

The incidence of deep vein thrombosis (DVT) after non-myeloablative (NMA) allogeneic stem cell transplantation (allo-SCT) is unknown. In addition, very few studies on the predisposing factors for DVT post SCT have been published. The incidence of DVT among patients that underwent NMA allo-SCT at our hospital was 4.1% (3 of 73) over the course of last 8 years, and to the best of our knowledge this is the first study to report the incidence of DVT following NMA allo-SCT. The present findings show that NMA allo-SCT patients may have multiple risk factors for DVT. Herein we present 3 cases of DVT following NMA allo-SCT and a literature review.

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Çocukluk çaðýnda böbrek kökenli lenfoma sýklýkla bilateral kitle lezyonlarý, daha az sýklýkla da tek veya retroperitoneal bir kitle olarak veya difüz infiltratif lezyonlar þeklinde dikkate gelebilir. Tanýnýn gecikmemesi adýna, santral sinir sistemi tutulumu bulgularý olan hastalarda, diðer fizik ve laboratuar bulgularýna da yeterince dikkat edilmesi zorunludur. Bu yazýda, renal lenfomasý olan ancak santral sinir sistemi bulgularý ile prezente olduðundan taný konulmasýnda gecikilen bir çocuk hasta sunulmuþtur.

In pediatric patients renal lymphoma frequently presents in the form of multiple, bilateral mass lesions, infrequently as a single or retroperitoneal mass, and rarely as diffuse infiltrative lesions. In patients with apparent central nervous system involvement close attention to other physical and laboratory findings are essential for preventing a delay in the final diagnosis. Herein we present a pediatric patient with renal lymphoma that presented with central nervous system findings that caused a delay in diagnosis.

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Aðýr otoimmün hemolitik anemili bir kadýn hasta 18 ay konvansiyonel kortizon (2 mg/kg/gün bölünmüþ dozlarda) uygulamasýna cevap vermeyince splenektomi planlandýðý için bize baþvurdu. Oral megadoz metilprednizolon (MDMP; 30 mg/kg/gün 3 gün, 20 mg/kg/gün 4 gün verildikten sonra haftada 10, 5, 2 ve 1 mg/kg/gün dozlarda) sabah 6’da verilmesi ile kýsa sürede Coombs pozitifliði devam etmesine raðmen hemoliz durdu ve hematolojik bulgular düzeldi. Son 18 aydan beri tedavi almayan hastada Coombs pozitifliði devam etmekte ise de hemoliz olmaksýzýn þikâyetsiz olarak yýlda bir kere kontrole gelmek üzere takip edilmektedir.

A female in the Netherlands with severe autoimmune hemolytic anemia (AIHA) was treated with conventional corticosteroid (2 mg/kg/d in divided doses) and blood transfusions for 18 months without improvement. The presented patient responded to megadose methylprednisolone (MDMP) 30 mg/kg/d for 3 d, followed by 20 mg/kg for 4 d, and subsequently 10, 5, 2, and 1 mg/kg/d each for 1 week.

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Langerhans hücreli sarkom malign sitolojik görünümlü ve Langerhans fenotipine sahip nadir görülen yüksek dereceli neoplazmdýr. Biz, sað aksiller bölgede büyümüþ aðrýsýz kitlesi olan 65 yaþýnda Langerhans hücreli sarkom olgusunu sunduk ve Langerhans hücreli sarkomun tanýsal ve histopatolojik özelliklerini literatür eþliðinde gözden geçirdik.

Langerhans cell sarcoma is a rare, high-grade neoplasm with overtly malignant cytological features and the Langerhans phenotype. Herein, we present a rare case of Langerhans cell sarcoma in a 65-year-old female that presented with a painless enlarging mass in her right axillary region, along with the histopathological features and diagnostic characteristics in the light of literature on Langerhans cell sarcoma.

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Önceden akut myelomonositik lösemi(M4) tanýsý almýþ 50 yaþýndaki erkek hastaya, Temmuz 2009’da allojenik hematopoietik kök hücre nakli yapýldý (AHKHN). Nakil öncesi dönemde, tam kan sayýmý, karaciðer ve böbrek fonksiyon testleri, koagulasyon parametreleri ve diðer ölçümler normal bulundu. Naklin birinci gününde,orofaringeal candidiasisle birlikte aðýz içindeki beyaz plaklar ve ayrýca perianal eritem nedeniyle hastaya intravenöz teikoplanin (ilk 3 gün 400mg/ gün ve sonrasýnda günde 400mg) ve kaspofungin (ilk doz 1x70 mg/gün ve sonrasýnda 1x50 mg/gün) baþlandý. Naklin 14.gününde,karýnda huzursuzluk, bulantý ve yorgunluk gibi þikayetlerle birlikte sulu diare ortaya çýktý. gaita incelemesinde kanama bulgusu yoktu. Tür-özgün IFA metodu ile nadir bir patojen olan Encephalitozoon intestinalis tesbiti doðrulandý ve 2x400 mg/gün albendazol tedavisi hemen baþlandý. Albendazol tedavisinin 5. gününde (naklin 18. günü), hastanýn karaciðer fonksiyon testleri (KCFT) bozulmaya baþladý. KCFT’nin bozulmasý devam ettiðinden, tedavinin 7. gününde albendazol kesildi. Naklin 22. gününde Kc biopsisi yapýlarak, taný patologlar tarafýndan ‘toxik hepatit’ olarak doðrulandý. KCFT albendazol tedavisinin kesilmesinden sonra hýzla düzelmeye baþladý. albendazol tedavi sürecinin 13.gününde tüm KCFT deðerleri normale döndü. Bu vaka; AHKHN yapýlmýþ bir hastada nadir diare etkeni - Encephalitozoon intestinalis- ile albendazol tedavisi sýrasýnda geliþen hepatotoksisiteyi göstermektedir. Ayrýca, IFA metodu ile Türkiye’den bildirilen ilk E. intestinalis vakasýdýr.

A 50-year-old male patient previously diagnosed with acute myelomonocytic (M4) leukemia in July 2009 underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the pre-transplant period complete blood count (CBC), liver and renal function tests, coagulation tests, and other parameters were normal. On the first day of transplantation teicoplanin (400 mg d–1 for the first 3 d, and then 400 mg d-1) and caspofungin (first dose was 1×70 mg d–1, followed by 1×50 mg d–1) were started intravenously due to white plaques and oropharyngeal candidiasis in the patient’s mouth and perianal erythema. On the 14th d of transplantation watery diarrhea occurred, along with abdominal discomfort, nausea, and fatigue. Stool examination was negative for findings of bleeding. Investigation of Microsporidia confirmed a rare pathogen Encephalitozoon intestinalis in the patient’s stool sample via species-specific immunofluorescence antibody (IFA) assay and albendazole treatment was started at a dose of 2×400 mg d–1. On the 5th d of albendazole treatment (d 18 of treatment) liver function test (LFT) results began to deteriorate. As LFT results continued to deteriorate, albendazole was withdrawn on the 7th d of treatment. Biopsy was performed on the 22nd d of transplantation and histopathological analysis confirmed the diagnosis of toxic hepatitis. LFT results began to decrease after withdrawal of albendazole treatment. On the 13th d of albendazole treatment all LFT values returned to normal. The presented allo-HSCT case had a rare pathogenic agent (E. intestinalis) that caused diarrhea, as well as hepatotoxicity due to albendazole treatment. This is the first reported case of E. intestinalis diagnosed via IFA in Turkey.

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