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    Manganese(III) Acetate-Based Radical Cyclization Reactions for Pyranocoumarin and Pyranoquinoline Compounds: Synthesis, DFT and Molecular Docking Studies
    (Wiley-V C H Verlag Gmbh, 2022) Yakut, Mehtap; Yilmaz, Mehmet; Pekel, Tarik; Erkan, Sultan; Katirci, Ramazan; Bicer, Emre
    Pyranofuroquinoline and pyranofurocoumarin derivatives are significant class of compounds due to being useful in many diverse applications. The synthesis of the compounds are succeeded in one step by radical cyclization reaction in the presence of manganese(III) acetate. Furoquinoline and furocoumarin reactants were used together with 1,1-disubstituted-, 1,2-disubstituted and cyclic alkenes giving pyranofuroquinoline and pyranofurocoumarin compounds in moderate to high yields. Also, we were able to isolate alkenyl and acetoxy- side-products in minor low yields. The electronic and optical features of furoquinoline and furocoumarin reactants and pyranofuroquinoline products were inquired using theoretical approaches (DFT and TD-DFT). Their excitation and emission spectrums were computed. The results revealed that the pyranofuroquinoline molecules did not show the energy transfer feature. It was observed that the behavior of nonlinear optic of furoquinoline is higher than the pyranofuroquinoline and furocoumarin molecules. But the average polarization and the anisotropy of the polarizability of pyranofuroquinoline increased and was found to be 262.7 and 141.9 respectively. Also, according to the calculated docking parameters, the investigated pyranofuroquinoline and pyranofurocoumarin compounds were found to have higher activity than the substances with anticancer and antibacterial standards.
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    Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy
    (WILEY, 2015) Hacioglu, Sibel; Bilen, Yusuf; Eser, Ali; Sivgin, Serdar; Gurkan, Emel; Yildirim, Rahsan; Aydogdu, Ismet; Dogu, Mehmet Hilmi; Yilmaz, Mehmet; Kayikci, Omur; Tombak, Anil; Kuku, Irfan; Celebi, Harika; Akay, Meltem Olga; Esen, Ramazan; Korkmaz, Serdal; Keskin, Ali
    In this multicenter retrospective analysis, we aimed to present clinical, laboratory and treatment results of 94 patients with Hairy cell leukemia diagnosed in 13 centers between 1990 and 2014. Sixty-six of the patients were males and 28 were females, with a median age of 55. Splenomegaly was present in 93.5% of cases at diagnosis. The laboratory findings that came into prominence were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an indication for treatment were treated with cladribine as first-line treatment. Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate after cladribine was 16.6%, and treatment related mortality was 2.5%. Most preferred therapy ( 95%) was again cladribine at second-line, and third line with CR rate of 68.4% and 66.6%, respectively. The 28-month median OS was 91.7% in all patients and 25-month median OS 96% for patients who were given cladribine as first-line therapy. In conclusion, the first multicenter retrospective Turkish study where patients with HCL were followed up for a long period has revealed demographic characteristics of patients with HCL, and confirmed that cladribine treatment might be safe and effective in a relatively large series of the Turkish study population. Copyright (C) 2014 John Wiley & Sons, Ltd.
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    Nodular lymphocyte predominant Hodgkin's lymphoma in daily practice: A multicenter experience
    (WILEY, 2018) Gemici, Aliihsan; Aydogdu, Ismet; Terzi, Hatice; Sencan, Mehmet; Aslan, Alma; Kaya, Ali Hakan; Dal, Mehmet Sinan; Akay, Meltem Olga; Dogu, Mehmet Hilmi; Ayyildiz, Orhan; Sahin, Fahri; Cagliyan, Gulsum Akgun; Yilmaz, Mehmet; Gokgoz, Zafer; Bilen, Yusuf; Demir, Cengiz; Sevindik, Omur Gokmen; Korkmaz, Serdal; Eser, Bulent; Altuntas, Fevzi
    Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin's lymphoma. In this study, we aimed to investigate the clinical features and therapeutic outcomes of patients with NLPHL who were diagnosed at different institutes in Turkey. We retrospectively reviewed the records of the patients diagnosed with NLPHL. Adult patients who were diagnosed after 2005 with histological confirmation were selected for the study. Forty-three patients were included in the study. Median age of patients was 37.5years (18-70) at the time of diagnosis. About 60.5% patients were diagnosed as stage I and II NLPHL, and remaining 39.5% had stage III and IV disease. Median follow-up was 46months. During follow-up, none of the patients died. Seven patients relapsed or progressed after initial therapy at a median of 12months. Five of 7 relapsed/refractory patients (71.4%) were salvaged with chemotherapy only (DHAP, ICE), and the remaining 2 (28.6%) were salvaged with chemoimmunotherapy. All of relapsed/refractory patients were able to achieve complete remission after salvage therapy. Lactate dehydrogenase levels were significantly higher in patients with progressive disease compared with nonprogressive disease. Our study showed an excellent outcome with all patients alive at last contact with a median follow up of 46months despite a wide range of different therapeutic approaches. All relapsed and refractory patients were successfully salvaged despite a low frequency of patients received immunotherapy in conjunction with chemotherapy. Our results suggest that immunotherapy may be reserved for further relapses.
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    Primary central nervous system lymphoma in daily practice and the role of autologous stem cell transplantation in relapsed disease: A retrospective multicenter study
    (PERGAMON-ELSEVIER SCIENCE LTD, 2016) Erkurt, Mehmet Ali; Berber, Ilhami; Tekgunduz, Emre; Dogu, Mehmet Hilmi; Korkmaz, Serdal; Demir, Cengiz; Yilmaz, Mehmet; Akay, Olga Meltem; Pala, Cigdem; Bilen, Yusuf; Kaya, Emin; Sari, Ismail; Sencan, Mehmet; Kuku, Irfan; Altuntas, Fevzi; Dal, Mehmet Sinan; Aydogdu, Ismet
    We investigated the course of 54 patients presenting with primary central nervous system lymphoma, who were treated in daily practice. The patients were treated with chemotherapy and/or radiotherapy and/or intrathecal chemotherapy. At a median follow-up period of 23 months (range 1-71), median relapse-free survival (RFS) and overall survival (OS) were not reached. Estimated 2-year RFS and OS rates were 42% and 48%, respectively. Ten relapsed PCNSL patients underwent ASCT. Complete remission rate of these patients was 40%, with 20% treatment-related mortality. Estimated 2-year RFS and OS rates were 37% and 40%, respectively. The prognosis of patients with PCNSL, who received off-study treatment, is still dismal. (c) 2016 Elsevier Ltd. All rights reserved.
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    The Observation on Bohemian Lifes of Poets
    (Selcuk Univ, Inst Turkish Studies, 2014) Yilmaz, Mehmet
    The Opinion about the fact that an artist has got a different creation and mental structure has made think that his life is different from ordinary individuals too. The artist who got far from common rules and mediocrity in social structure was seen as inconsistent, that he got far from ethics of community has caused he is rejected time after time. Especially the term Bohemian which is used relating to life style in artist world of french community has been a symbol which is difference from a determined group in terms of social structure. In this study a bohemian focussing on poet has been analyzed. In addition to some works in turkish literature searching this subject, the souvenirs reflecting private life of authors in the frame of Bohemian have been searched.
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    Therapeutic plasma exchange in patients with neurological diseases: Multicenter retrospective analysis
    (Pergamon-Elsevier Science Ltd, 2013) Kaya, Emin; Keklik, Muzaffer; Sencan, Mehmet; Yilmaz, Mehmet; Keskin, Ali; Kiki, Ilhami; Erkurt, Mehmet Ali
    Therapeutic plasma exchange (TPE), is a procedure, changing pathologic substances in the plasma of patients with replacement fluid. TPE has an increasing list of indications in recent years such as neurological, connective tissue, hematological, nephrological, endocrinological and metabolic disorders. We report our multicenter data about therapeutic plasma exchange in patients with neurological diseases. Six University Hospitals' aphaeresis units medical records about neurologic diseases were reviewed retrospectively. Hundred and fifteen patients and 771 TPE sessions from six aphaeresis units' were included to this study. Of the 115 patients, 53 (46%) were men and 62 (54%) were women. The median age was 50 (range: 5-85) years. Of these patients 58.3% were Guillain-Barre syndrome (GBS), 17.4% were acute disseminated encephalomyelitis (ADEM), 10.4% were chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 7% were multiple sclerosis, 6.1% were myasthenia gravis (MG) and 0.9% were Wilson disease (WD). The median number of TPE sessions per patient was 5 (range 1-72). Human albumin was used as a replacement fluid in 66% and fresh frozen plasma was used in 34% of cases. TPE was done through central venous catheters in 66%, and peripheral venous access in 34% of patients. Some complications were seen in patients (18.3%) during TPE sessions. These complications were, complications related to catheter placement procedure (8.7%), hypotension (3.5%), hypocalcaemia (3.5%) and allergic reactions (1.7%). The complication ratios were 2.7% in total 771 TPE procedures. TPE procedure was terminated in 6% of sessions depending on these complications. Overall responses to TPE were noted in 89.5% of patients. In conclusion: Therapeutic plasma exchange is an effective treatment option in several neurologic diseases. (C) 2013 Elsevier Ltd. All rights reserved.
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    Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: A retrospective multicenter study
    (PERGAMON-ELSEVIER SCIENCE LTD, 2013) Korkmaz, Serdal; Keklik, Muzaffer; Sivgin, Serdar; Yildirim, Rahsan; Tombak, Anil; Kaya, Mehmet Emin; Acik, Didar Yanardag; Esen, Ramazan; Hacioglu, Sibel Kabukcu; Sencan, Mehmet; Kiki, Ilhami; Tiftik, Eyup Naci; Kuku, Irfan; Okan, Vahap; Yilmaz, Mehmet; Demir, Cengiz; Sari, Ismail; Altuntas, Fevzi; Unal, Ali; Ilhan, Osman
    Thrombotic thrombocytopenic purpura (TIT) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. UP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of UP. Also, UP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in UP patients. Aim: We aimed to present our experience in 163 patients with UP treated with TPE during the past 5 years from 10 centers of Turkey. Patients and methods: One hundered and sixty-three patients with UP treated with TPE during the past 5 years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1-1.5 times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150 x 10(9)/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. Results: Fifty-eight percent (95/163) of the patients were females. The median age of the patients was 42 years (range; 16-82). The median age of male patients was significantly higher than female (53 vs. 34 years; p < 0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary UP comprised of 85.9% (140/163) of the patients and secondary UP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary UP. The median number of TPE was 13 (range; 1-80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p < 0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary UP (85% vs. 87%, respectively; p = 0.806). There was no advantage of TPE + prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p = 0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TIT [15% (21/140) vs. 13% (3/23); p = 0.8061. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE + prednisolone [14% (12/86) vs. 3% (2/67), p < 0.001]. Conclusions: TPE is an effective treatment for UP and is associated with high CR rate in both primary and secondary UP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of UP and if these two criteria met in a patient, TPE should be performed immediately. (C) 2013 Elsevier Ltd. All rights reserved.
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    What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)?
    (ELSEVIER IRELAND LTD, 2018) Kayikcioglu, Meral; Tokgozoglu, Lale; Dogan, Volkan; Ceyhan, Ceyhun; Tuncez, Abdullah; Kutlu, Merih; Onrat, Ersel; Alici, Gokhan; Akbulut, Mehmet; Celik, Ahmet; Yesilbursa, Dilek; Sahin, Tayfun; Sonmez, Alper; Ozdogan, Oner; Temizhan, Ahmet; Kilic, Salih; Bayram, Fahri; Sabuncu, Tevfik; Coskun, Fatma Yilmaz; Ildizli, Muge; Durakoglugil, Emre; Kirilmaz, Bahadir; Yilmaz, Mehmet Birhan; Yigit, Zerrin; Yildirim, Aytul Belgi; Gedikli, Omer; Topcu, Selim; Oguz, Aytekin; Demir, Mesut; Yenercag, Mustafa; Yildirir, Aylin; Demircan, Sabri; Yilmaz, Mehmet; Kaynar, Leyla Gul; Aktan, Melih; Durmus, Rana Berru; Gokce, Cumali; Ozcebe, Osman Ilhami; Akyol, Tulay Karaagac; Okutan, Harika; Sag, Saim; Gul, Ozen Oz; Salcioglu, Zafer; Altunkeser, Bulent Behlul; Kuku, Irfan; Yasar, Hurriyet Yilmaz; Kurtoglu, Erdal; Kose, Melis Demir; Demircioglu, Sinan; Pekkolay, Zafer; Ilhan, Osman; Can, Levent H.
    Background and aims: Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of largescale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2). Methods: A-HIT1 is a survey of homozygous FH patients undergoing low density lipoprotein (LDL) apheresis (LA). A-HIT2 is a registry of adult FH patients (homozygous and heterozygous) admitted to outpatient clinics. Both registries used clinical diagnosis of FH. Results: A-HIT1 evaluated 88 patients (27 +/- 11 years, 41 women) in 19 centers. All patients were receiving regular LA. There was a 7.37 +/- 7.1-year delay between diagnosis and initiation of LA. LDL-cholesterol levels reached the target only in 5 cases. Mean frequency of apheresis sessions was 19 +/- 13 days. None of the centers had a standardized approach for LA. Mean frequency of apheresis sessions was every 19 +/- 13 (7-90) days. Only 2 centers were aware of the target LDL levels. A-HIT2 enrolled 1071 FH patients (53 +/- 8 years, 606 women) from 31 outpatients clinics specialized in cardiology (27), internal medicine (1), and endocrinology (3); 96.4% were heterozygous. 459 patients were on statin treatment. LDL targets were attained in 23 patients (2.1% of the whole population, 5% receiving statin) on treatment. However, 66% of statin-receiving patients were on intense doses of statins. Awareness of FH was 9.5% in the whole patient population. Conclusions: The first nationwide FH registries revealed that FH is still undertreated even in specialized centers in Turkey. Additional effective treatment regiments are urgently needed.