A correlation between the genotype and clinical course in hemophilia B patients

Çolakoğlu, S. (Arel Author), Berber, Ergül (Arel Author)

Sex-change surgery in a type 3 VWD patient

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A cost evaluation of treatment alternatives in mild-to-moderate bleeding episodes in haemophilia patients with inhibitors in Turkey

A decision-analysis model was constructed to assess total direct health care costs of four current first-line treatment options for mild-to-moderate bleeding episodes in haemophilia patients with inhibitors in Turkey: recombinant activated Factor VII (rFVIIa); high-dose Factor VIII; prothrombin complex concentrate (PCC); and activated PCC (aPCC). Resource utilisation was based on a retrospective analysis of 105 bleeding episodes treated during the period January 1996 to December 2002. Clinical outcomes were derived from a combination of the retrospective patient data and literature review, both validated by an expert panel of Turkish haematologists. rFVIIa was more effective and resolved bleeds more quickly than any of the alternatives. rFVIIa and PCC were associated with similar direct treatment costs that were relatively lower than those compared with the other options. Given the better efficacy, rFVIIa should be considered the preferred treatment option in the management of haemophilia patients with inhibitors in Turkey. © 2005 T&F Informa UK Ltd

A polymorphism in the IL-5 gene is associated with inhibitor development in severe hemophilia a patients [Agi{dotless}r hemofili a hastalari{dotless}nda i·nhibitör gelişimi ile IL-5 genindeki bir polimorfizmin i·lişkilendirilmesi]

Objective: A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-ß1), and interferon gamma (IFN-?) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene. Materials and Methods: A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-ß1, and IFN-? in 103 patients and 100 healthy individuals was carried out. Results: An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele. Conclusion: The lack of other variants in the IL-5 gene of patients and controls suggests that rs2069812 may be a regulatory SNP and may have a role in B-lymphocyte development, constituting a genetic risk factor in antibody development

A probabilistic seismic hazard assessment for the Turkish territory—part I: the area source model

The seismic zoning map of Turkey that is used in connection with the national seismic design code (versions issued both in 1997 and 2007) is based on a probabilistic seismic hazard assessment study conducted more than 20 years ago (Gülkan et al. in En son verilere göre hazırlanan Türkiye deprem bölgeleri haritası, Report No: METU/EERC 93-1, 1993). In line with the efforts for the update of the seismic design code, the need aroused for an updated seismic hazard map, incorporating recent data and state-of-the-art methodologies and providing ground motion parameters required for the construction of the design spectra stipulated by the new Turkish Earthquake Design Code. Supported by AFAD (Disaster and Emergency Management Authority of Turkey), a project has been conducted for the country scale assessment of the seismic hazard by probabilistic methods. The present paper describes the probabilistic seismic hazard assessment study conducted in connection with this project, incorporating in an area source model, all recently compiled data on seismicity and active faulting, and using a set of recently developed ground motion prediction equations, for both active shallow crustal and subduction regimes, evaluated as adequately representing the ground motion characteristics in the region. The area sources delineated in the model are fully parameterized in terms of maximum magnitude, depth distribution, predominant strike and dip angles and mechanism of possible ruptures. Resulting ground motion distributions are quantified and presented for PGA and 5 % damped spectral accelerations at T = 0.2 and 1.0 s, associated with return periods of 475 and 2475 years. The full set of seismic hazard curves was also made available for the hazard computation sites. The second part of the study, which is based on a fault source and smoothed seismicity model is covered in Demircioglu et al. in Bull Earthq Eng, (2016).AFA