Akut koroner sendrom hastalarında serum gama glutamil transferaz değerinin prognostik önemi

Kardiyovasküler mortalite ve morbiditenin en önemli sebeplerinden biri olan akut koroner sendrom (AKS)’ların patofizyolojisindeki temel olay, aterom plağının kararsız hale gelmesi, sonra da yırtılmasıdır. Bu asamalarda oksidasyon ve inflamasyonun çok önemli yeri vardır. Yapılan çalısmalarda gama glutamil transferaz (GGT)’nin aterom plağı içindeki oksidatif ve inflamatuar reaksiyonlara katıldığı gösterilmistir. Bu çalısmanın amacı, AKS tanısı alan hastalarda bakılan bazal serum GGT değerinin koroner yoğun bakım (KYB) takibinde (MĐKO-YB) ve bir aylık izlemde (MĐKO-AY) istenmeyen olay gelisimine etkisini değerlendirmektir. Çalısmamıza AKS tanısı ile KYB’a yatırılan 117 hastayı aldık. Karaciğer fonksiyon testlerinde bozukluk, aktif hepatobilier ya da ciddi sistemik hastalığı olan bireyleri çalısmadan dısladık. Hastaların yas ortalaması 57 ± 8 yıl olup, 93’ü erkekti (%79.5). MĐKO-AY gelisen hastalarda diabetes mellitus, dökümante koroner arter hastalığı ve koroner bypass öyküsü anlamlı olarak daha fazlayken (p değerleri sırasıyla 0.045, 0.034 ve 0.049), laboratuvar değerlerinden bazal GGT, total kolesterol ve düsük dansiteli lipoprotein (LDL) anlamlı olarak daha yüksek (p değerleri sırasıyla 0.022, 0.013 ve 0.028), ejeksiyon fraksiyonu (EF) ise anlamlı olarak daha düsüktü (p=0.018). Ayrıca yası 70’in üzerinde olanlarda MĐKOAY gelisimi, 70’in altında olanlara göre anlamlı olarak daha fazlaydı (p=0.015). ‘‘Receiver operator characteristic curve’’ analizi ile sınır değerleri bazal GGT için 25 u/l, LDL için 100 mg/dl, EF için %40 olarak hesaplandı. Çoklu Cox regresyon analizinde MĐKO-AY gelisiminin bağımsız belirleyicileri; yasın 70’in üstünde olması, EF’nin %40’ın altında olması ve LDL’nin 100 mg/dl’nin üzerinde olmasıydı (p değerleri sırasıyla 0.041, 0.005 ve 0.007). MĐKO-YB gelisen hastalarda ise miyokard infarktüsü öyküsü ve bazal GGT anlamlı derecede daha fazla iken (p değerleri sırasıyla 0.050 ve 0.002), EF daha düsüktü (p=0.023). Çoklu Cox regresyon analizinde MĐKO-YB gelisiminin bağımsız belirleyicisi olarak sadece bazal GGT’nin 25 u/l’nin üzerinde olması bulundu (p=0.004). Sonuç olarak, bazal GGT, MĐKO-YB gelisimi için bağımsız belirleyici iken, MĐKO-AY gelisimi için bağımsız belirleyici değildi

Hand-held echocardiography during complex electrophysiologic procedures

Introduction: Complex electrophysiologic (EP) procedures are time consuming and open to complications. Accurate and rapid recognition of cardiac pathologies is essential before, during, and immediately after such procedures. In this study, we aimed to compare hand-held echocardiography (HHE) with standard echocardiography (SE) to determine whether HHE can be used as a practical and reliable diagnostic tool during such procedures. Methods: One hundred consecutive patients undergoing complex EP procedures and catheter ablation were included in the study. All patients were evaluated with SE or HHE in terms of main cardiac pathologies at the beginning and immediately after the procedure. The diagnostic accuracy and evaluation time of both methods were compared at the beginning and after the procedure. The agreement between both methods was calculated. Results: At the beginning and after the procedure, opening and evaluation times with HHE were significantly shorter than with SE (P<0.001 for all). There was significant agreement between the two methods in the diagnosis of cardiac pathologies (Agreement was 95% for minimal mild aortic regurgitation (AR), 99% for moderate/ severe AR, 93% for minimal/ mild mitral regurgitation (MR), 95% for moderate/ severe MR, 100% for pericardial effusion, and 100% for left ventricular thrombus at the beginning of the procedure). Conclusion: With the use of HHE during complex EP procedures, cardiac pathologies can be diagnosed with similar accuracy as SE. In addition, HHE has a significant advantage over SE in terms of time to diagnosis

Association and Haplotype Analysis of the PON1, ITGB3 and CYP3A4 Genes, Strong Candidates for Familial Coronary Artery Disease Susceptibility

Objective: Genetic predisposition is very common among the patients with coronary artery disease (CAD), a complex and multifactorial disease. Our objective was to determine the possible association between the most remarkable functional variants in the paraoxonase 1(PON1), cytochrome P450 3A4 (CYP3A4), integrin subunit beta 3 (ITGB3) genes and familial CAD. Materials and Methods: We included 117 patients diagnosed with familial CAD and 99 healthy subjects with no family history of CAD. PON1 Q192R, PON1 L55M, CYP3A4*1G and ITGB3 L33P single nucleotide polymorphisms were genotyped using the Sequenom MassARRAY system. Results: Comparison of genotype and allele frequencies in inheritance models of polymorphisms between the patient and control groups did not reveal any significant findings related to CAD. Stratified analysis by gender did also not display any association both in females and males. There was no significant difference in the frequencies of the haplotypes of the PON1 Q192R and L55M polymorphisms between the groups. Conclusions: Our findings confirmed previous studies that did not consider PON1, CYP3A4 and ITGB3 genes as risk loci. The fact that our study was conducted only in patients with familial CAD shows the originality and importance of our results

Osteosarkomun Neo-adjuvan tedavisindeki deneyimimiz

Aim: Effective adjuvant or neo-adjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. In this study, the efficacy and tolerability of cisplatin and doxorubicin combination regimen as a neoadjuvant therapy of osteogenic sarcoma were investigated. Methods: From Jan 1999 to Jan 2003, 15 patients with osteosarcoma of the extremity and non-metastatic at presentation, were treated according to the following scheme: primary chemotherapy with cisplatinum 100 mg/m2 day 1 at 3-week intervals and doxorubicin 25mg/m2 day 1,2,3 at 3-week intervals, resection of primary tumor and adjuvant chemotherapy. . Results: Five (33%) patients achieved good response as a tumor necrosis ratio. Five-year event-free survival (EFS) and overall survival (OS) were 66% and 80%, respectively. 11 (73%) patients were performed limb salvage surgery. Neo-adjuvant chemotherapy regimen was well tolerated.Conculusion: dsplatin and doxorubicin combination regimen is considered as a reasonable option for neo-adjuvant treatment of patients with osteogenic sarcoma.Amaç: Adjuvan veya neo-adjuvan kemoterapi rejimleri, tanı anında ekstremiteye sınırlı yüksek gradeli osteosarkom hastalarının prognozunu dramatik şekilde iyileştirmiştir. Çalışmamızda osteosarkomda neo-adjuvan olarak uygulanan sisplatin ve doksorubisin kombinasyonunun etkinliğini ve tolerabilitesini incelemek amaçlanmıştır. Yöntem: Ocak 1999 ve Ocak 2003 arasında, ekstremite yerleşimli osteosarkom tanılı 15 hasta, neo-adjuvan sisplatin 100 mg/m2 1. gün, 3 haftada bir ve doksorubisin 25 mg/mz 1., 2. ve 3. günler 3 haftada bir uygulanan kombine kemoterapi rejimi sonrası primer tümörü rezeke edilerek ve adjuvan kemoterapi uygulanarak tedavi edildi. Bulgular: 5 (%33) hastada, tümör nekroz oranlarına göre iyi cevap elde edildi. 5 yıllık hastalıksız sağ kalım %66, genel sağ kalım %80 olarak hesaptandı. 11 (%73) hastaya ekstremite koruyucu cerrahi uygulandı. Neo-adjuvan kemoterapi rejimi hastalar tarafından iyi tolere edildi. Sonuç: Sisplatin ve doksorubisin kombinasyon r;jimi, osteosarkomun neo-adjuvan tedavisinde uygun tedavi seçeneği olarak düşünülebilir

The CYP2C19*2 and CYP2C19*17 Polymorphisms play a Vital Role in Clopidogrel Responsiveness after Percutaneous Coronary Intervention: A Pharmacogenomics Study

Clopidogrel inhibits platelet activation and aggregation by blocking the P2Y12 receptor. Dual antiplatelet therapy with clopidogrel and aspirin is recommended treatment by current guidelines for patients undergoing percutaneous interventions. Recurrent ischaemic cardiac events after this treatment showed lack of clopidogrel responsiveness. We aimed to investigate the most noticeable variants in the genes involved in clopidogrel pharmacokinetics and pharmacodynamics. A total of 347 Turkish patients who underwent percutaneous coronary interventions with stent implantation were included in our study. Platelet reactivity (PRU) and % inhibition were measured with VerifyNow P2Y12 assay in blood samples collected from patients who took a standard dose of clopidogrel (75 mg/day) for at least 7 days. The variants in the CYP2C19, CYP3A4, CYP2B6, ABCB1, ITGB3 and PON1 genes were genotyped using the Sequenom MassARRAY system. When grouped, the patients with PRU values >208 as non-responsiveness to clopidogrel therapy; 104 (30%) patients were non-responders and 243 (70%) patients were responders. A significant association was found between the CYP2C19*2 (G636A) polymorphism and non-responsiveness to clopidogrel therapy (p < 0.001). An allele frequency of this single nucleotide polymorphism was high in non-responders; its odds ratio was 2.92 compared with G allele (p < 0.001). PRU values of CT genotypes were lower (p = 0.029) and % inhibition values of CT genotypes were higher (p = 0.008) compared with CC genotypes for the CYP2C19*17 (C806T) polymorphism. None of the other genetic variants were found to be statistically associated with non-responsiveness to clopidogrel and antiplatelet activity. Our findings suggest that the CYP2C19*2 polymorphism is associated with non-responsiveness to clopidogrel therapy and the CYP2C19*17 polymorphism enhances antiplatelet activity of clopidogrel. Depending on haplotypes of these two polymorphisms, clopidogrel-treated patients can be protected or not from stent thrombosis and ischaemic events