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Öğe Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population(Lippincott Williams & Wilkins, 2017) Kayilioglu, Hulya; Kocak, Ulker; Karaer, Derya Kan; Percin, Emriye F.; Sal, Ertan; Tekkesin, Funda; Gursel, TurkizVincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A5*1/*3 genotype was 17.6%, it was 21.6% in the CYP3A5*3/*3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.Öğe Inherited coagulation disorders in Turkish children: A retrospective, single-center cohort study(PERGAMON-ELSEVIER SCIENCE LTD, 2020) Oner, Nergiz; Gursel, Turkiz; Kaya, Zuhre; Keskin, Ebru Yilmaz; Kocak, Ulker; Albayrak, Meryem; Yenicesu, IdilObjective: This study aims to investigate the distribution, clinical characteristics and outcome of inherited coagulation disorders (ICD) in Turkish children. Subjects and methods: Data from all children (age < 18 years) with ICD examined in our center were retrospectively reviewed. Results: There were 403 children with ICD (233 males and 170 females) with a median age of four years at diagnosis. The percentages of von Willebrand disease (vWd), hemophilia and rare bleeding disorders (RBD) were 40 %, 34 % and 26 %, type-1, type-2 and type-3 vWd were 63 % 17 % and 20 %, hemophilia A and B were 84 % and 16 %, and severe, moderate and mild hemophilia were 48 %, 30 % and 22 %, respectively. Factor VII and FXI deficiencies were the most prevalent, comprising 56 % and 22 % of all children with RBD, respectively. Parental consanguinity rates were 72 % in type-3 vWd and 61 % in severe RBD. The overall prevalence of gastrointestinal bleedings was 4.5 % (18/403), intracranial bleeding (ICB) was 4.96 % (20/403), mortality from ICB was 30 % (6/20) and the overall mortality rate was 1.49 % (6/403). No life-threatening bleeding was seen during regular prophylaxis. Chronic arthropathy prevalence in severe hemophilia was 8 % with primary prophylaxis and 53 % with demand therap. Inhibitor prevalence was 14 % in hemophilia-A and 5 % in hemophiliaB. Conclusions: These data show that vWd is the most common ICD, type-3 vWd and RBD are prevalent due to frequent consanguineous marriages and diagnosis of ICD is substantially delayed in Turkish children. Prophylactic replacement therapy prevents occurrence of life-threatening bleedings and reduces the development of hemophilic arthropathy.Öğe MOTHERS' KNOWLEDGE, ATTITUDES, AND BEHAVIOUR CONCERNING CHILDHOOD CANCER IN A RURAL ANATOLIAN PROVINCE(Gazi Univ, Fac Med, 2009) Hizel, Selda; Toprak, Sule; Albayrak, Meryem; Sanli, Cihat; Kocak, UlkerPurpose: Cancer is a physical disease but it has mental and social components. It is usually perceived as an illness that suggests death involving feelings of guilt, panic, hostility, aggression, anxiety, loneliness, and helplessness. It was reported that 50% of the parents of cancer patients had psychiatric disorders and that 73% of these were depressive disorders. The main reason for the anxiety is the close association of the illness with death and a lack of knowledge about childhood cancers. The aim of this study was to evaluate the knowledge and attitudes and anxiety level of mothers regarding childhood cancers. Materials and Methods: This cross-sectional study examined 300 mothers of children who presented to Kirikkale University, Medical School, Pediatrics Department and two health centers in central Kirikkale. Questionnaires consisting of 38 questions were completed by a research assistant by face-to-face interviews after permission was obtained from the mothers. The mothers' knowledge was regarded as good if 8-10 of the 10 knowledge questions about cancer were answered correctly, while 4-7 indicated moderate knowledge and 0-3 poor knowledge. Results: At least one cancer patient in their close community was known to 40.3% of the mothers. Information on cancer was mostly obtained from healthcare centers (20.7%), the media (35.3%), friends and relatives (10.7%), or both the media and friends and relatives (33.3%). The most widely known childhood cancers were leukemia and lymphoma. The rate of cancer screening among the participants was 7.3% (n=22). There was no significant correlation between having a family member with cancer and undergoing screening for cancer (p>0.05). The three main reasons for cancer were stated as smoking, food, and alcohol. The rate of smoking among the mothers was 57% and smoking was more common among mothers with less knowledge although this difference was not statistically significant. Twenty-three percent of the participants thought that cancer could not be treated. Mostly mothers stated that they would feel great sorrow and would experience great anxiety if they had a child with cancer. Only 22.7% of the mothers had sufficient knowledge about cancer. Anxiety on a subject exists when the level of information is inadequate. However, we found no correlation between the anxiety levels and the level of information about cancer among the mothers. Moreover, 71.7% of the mothers stated that they would not tell their child if he or she were diagnosed with cancer, while 7.7% said that they would not know what to do in that situation. Conclusion: The level of kowledge about cancer among the public is inadequate and thisresults in subjective value judgments, which directly influence anxiety levels. Therefore, parents need to be informed more extensively about the prevention and treatment of cancer to decrease their anxiety.Öğe PERTUSSIS; STILL A CLINICAL DIAGNOSIS(Gazi Univ, Fac Med, 2006) Kocak, Ulker; Sanli, Cihat; Albayrak, Meryem; Bulduk, Reyhan Erol; Saygi, SemraPertussis is an acute, contagious respiratory infection characterized by paroxysmal coughing episodes. The most important and severe complication in infants is respiratory failure due to pneumonia. We report the case of a 3-month-old infant without any immunization who presented with cough, whooping and cyanosis, and developed pneumonia on the second day and a leukemoid reaction on the sixth day of admission. The relation between pneumonia and mortality, especially in infants, and the prognostic impact of a leukemoid reaction are emphasized.Öğe Prognostic Factors and Long-Term Outcome in 52 Turkish Children With Hemophagocytic Lymphohistiocytosis(Lippincott Williams & Wilkins, 2015) Kaya, Zuhre; Bay, Ali; Albayrak, Meryem; Kocak, Ulker; Yenicesu, Idil; Gursel, TurkizObjectives: Hemophagocytic lymphohistiocytosis is a syndrome of pathologic immune activation that shares similar clinical and laboratory phenotypes with severe sepsis. Recent studies led to better recognition of hemophagocytic lymphohistiocytosis by clinicians, but no consensus exists on the criteria for high-risk patients. Design: We retrospectively reviewed the medical records of patients diagnosed with hemophagocytic lymphohistiocytosis to analyze the risk factors associated with poor outcome. Setting: Pediatric intensive care and hematology units of three tertiary hospitals in Turkey. Participants: Fifty-two children with hemophagocytic lymphohistiocytosis. Interventions: None. Measurement and Main Results: There were a total of 52 children meeting the diagnostic criteria of Histiocytic Society. Of them, 28 (54%) had a primary hemophagocytic lymphohistiocytosis. Mutation studies were performed in 18 of 28 patients (65%). Fourteen of them had PRF1, STX11, STXBP2, and UNC13D mutations, and four had Rab27a and LYST mutations. The remaining 24 patients (46%) were defined as having secondary hemophagocytic lymphohistiocytosis. Twenty-one of them had infection-associated hemophagocytic lymphohistiocytosis, and three had lysinuric protein intolerance. The mortality rate was significantly higher in primary hemophagocytic lymphohistiocytosis (64%) than in secondary hemophagocytic lymphohistiocytosis (16%) (p < 0.05). There were no significant differences for survival rate between hemophagocytic lymphohistiocytosis 94 (44%) and hemophagocytic lymphohistiocytosis 2004 (64%) protocols (p > 0.05). Age below 2 years, hyperferritinemia, thrombocytopenia, high disseminated intravascular coagulation score at diagnosis, and no clinical response at 2 weeks of treatment were independent prognostic factors for poor prognosis. Conclusions: Our data suggest that disseminated intravascular coagulation score greater than or equal to 5 can be used in the definition of high-risk patients. Early recognition of poor risk factors has important prognostic and therapeutic implications.Öğe Remembering the Importance of an Old Friend: History Taking in Preoperative Evaluation of Healthy Children: A Single Center Experience(Gazi Univ, Fac Med, 2016) Toprak, Sule; Kocak, Ulker; Misirlioglu, Emine Dibek; Sanli, Cihat; Albayrak, Meryem; Basar, HulyaObjective: To investigate the consequences of routine laboratory tests that lead to surgical delay or high cost in patients with a normal medical history and physical examination who undergo minor surgical interventions. Patients and Method: Files of 1,322 patients aged between 0-16 years that had undergone elective surgical intervention within six years were reviewed. Results: Of the 1,322 patients, 1,246 (94.3%) had normal physical examination and laboratory findings. Seventy-six children who had abnormalities in laboratory findings and physical examination were referred to pediatrics. Of the 76 pediatric referees, 42 (55.3%) were reevaluated and were diagnosed with upper respiratory tract infection (n=23; 30.2%), iron deficiency anemia (n=5; 6.5%), innocent murmur (n=4; 5.3%), thalassemia minor (n=2; 2.6%), lower respiratory tract infection (n=2; 2.6%), urinary tract infection (n=1; 1.3%), mumps (n=1; 1.3%), acute gastroenteritis (n=1; 1.3%), minimal aortic and tricuspid valve insufficiency (n=1; 1.3%), minimal aortic stenosis (n=1; 1.3%), atrial septal defect (n=1; 1.3%). Surgical interventions were delayed until the recovery of the infectious diseases. In 25 of the patients, repeated tests showed normal ranges after the second test; however nine (n=9) of the patients showed increased or decreased numbers of white blood cell counts and whose medical history and physical examination revealed signs and symptoms related to infection. Conclusion: Routine laboratory tests contribute little to preoperative evaluation of children with normal history and physical examination undergoing low grade surgery.Öğe Severe Myelotoxicity Associated with Thiopurine S-Methyltransferase*3A/*3C Polymorphisms in a Patient with Pediatric Leukemia and the Effect of Steroid Therapy(Galenos Yayincilik, 2014) Belen, Burcu Fatma; Gursel, Turkiz; Akyurek, Nalan; Albayrak, Meryem; Kaya, Zuhre; Kocak, UlkerMyelosuppression is a serious complication during treatment of acute lymphoblastic leukemia and the duration of myelosuppression is affected by underlying bone marrow failure syndromes and drug pharmacogenetics caused by genetic polymorphisms. Mutations in the thiopurine S-methyltransferase (TPMT) gene causing excessive myelosuppression during 6-mercaptopurine (MP) therapy may cause excessive bone marrow toxicity. We report the case of a 15-year-old girl with T-ALL who developed severe pancytopenia during consolidation and maintenance therapy despite reduction of the dose of MP to 5% of the standard dose. Prednisolone therapy produced a remarkable but transient bone marrow recovery. Analysis of common TPMT polymorphisms revealed TPMT *3A/*3C.
