Browsing by Author "Yilmaz, C"
Now showing 1 - 13 of 13
Results Per Page
Sort Options
Item AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cellsYurekli, BS; Karaca, B; Kisim, A; Bozkurt, E; Atmaca, H; Cetinkalp, S; Ozgen, G; Yilmaz, C; Uzunoglu, S; Uslu, R; Saygili, FPurpose Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.Item Two siblings with horizontal gaze palsy and ROBO3 gene mutation: A double case studyOrak, SA; Erdogan, M; Yilmaz, C; Atasever, AK; Kubur, CC; Polat, MHorizontal gaze palsy along with progressive scoliosis (HGPPS) is rare and autosomal recessive disease related to the mutations in the ROBO3 gene located on chromosome 11q23-25. We present here two siblings from parents of consanguineous marriage, who were diagnosed with bilateral horizontal gaze restriction and scoliosis associated with homozygous mutation within ROBO3 gene and at the same time having neuroimaging findings. With HGPSS's typical findings, we detected a homozygous c.1366G> T (p.Gly456Ter) variant in the ROBO3 gene in our patients. HGPPS should be confirmed by ROBO3 gene analysis, and the brain MRI may be the first diagnostic technique.Item Epileptic Encephalopathy of Unknown Cause in Turkey Indicates a New Homozygous NAPB Gene VariantOrak, SA; Bilgiç, DG; Kubur,ÇÇ; Atasever, AK; Yilmaz, C; Polat, MIntroduction: As with many genetic diseases, the diagnostic role of next-generation sequencing is invaluable for early-onset epileptic encephalopathies. SNARE proteins in synaptic vesicles (synaptobrevin-2) and synaptic plasma membrane (syntaxin-1, SNAP-25) are involved in synaptic exocytosis and recycling. Patient Presentation: Here, we report a patient that started in early childhood with seizures resistant to antiepileptic drugs, then developed epileptic encephalopathy. Discussion/Conclusion: The NAPB gene encodes proteins in the SNARE complex. A previously unidentified homozygous missense variant in the NAPB gene may have contributed significantly to the etiology of our patient with epileptic encephalopathy. We also summarize the clinical, radiological, laboratory, and genetic findings of previously published patients with NAPB variants.Item A Neuroblastoma Case Presenting with Seizures Resistant to Anti-Epileptic TreatmentsKubur, ÇÇ; Orak, SA; Atasever, AK; Yilmaz, C; Polat, MSeizure is a rare symptom of paraneoplastic syndrome seen in neuroblastoma without a previous history. A 4-month-old male patient who was followed up with a preliminary diagnosis of an adrenal mass in pediatric oncology was admitted to hospital with a seizure. A diagnosis of undifferentiated neuroblastoma was made with a biopsy from an adrenal mass. Seizures were resistant to anti-epileptic therapy and they were completely under control with steroids on the 4th day of treatment. Electroencephalography (EEG) disturbances disappeared and no neurologic deficit was detected. This case, which presented with isolated seizure symptoms of neuroblastoma and was treated with steroids, was a very rare presentation in which symptoms and EEG disturbances disappeared. In neuroblastoma, autoimmunity may be involved in the pathogenesis of seizures, which is a rare finding of paraneoplastic syndrome and the option of immunotherapy should be considered.Item Evaluation of GFAP, S100B, and UCHL-1 Levels in Children With Refractory EpilepsyAksoy, HU; Yilmaz, C; Orak, SA; Ayça, S; Polat, MIntroduction A number of biomarkers are used to evaluate the duration of the epileptic seizure and the interictal period following neuronal injury. Invasive diagnostic methods are increasingly being replaced by peripheral or minimally invasive biomarkers that give results faster and are more secure.Purpose We aimed to evaluate serum glial fibrillary acidic protein (GFAP), S100B, and ubiquitin C-terminal hydrolase (UCHL-1) levels in children with epilepsy.Methods Our study included 3 groups: a nonrefractory epilepsy group, a refractory epilepsy group, and a control group. The GFAP, S100B, and UCHL-1 levels in serum samples collected 2-24 hours after the last seizure were analyzed using enzyme-linked immunosorbent assays.Results A total of 69 children participated in the study, with 35 participants in the refractory epilepsy group, 18 in the nonrefractory epilepsy group, and 16 in the control group. The GFAP values in the refractory (25.4 ng/mL) and nonrefractory (26.1 ng/mL) epilepsy groups were found to be statistically significantly higher than those in the control group (17.9 ng/mL; P = .001). The S100B values were found to be significantly higher in the refractory epilepsy group (34.13 pg/mL) than in both the control group and the nonrefractory epilepsy group (28.05 pg/mL; P = .028). No significant differences were observed in the UCHL-1 levels between the 3 groups.Conclusions We conclude that the observed differences may be due to the increased expression of S100B and GFAP caused by increased and repetitive neuronal damage in refractory epilepsies compared with nonrefractory epilepsies.Item Managing Strategic Logistics Partnerships With Total Relationship Management (TRM)Yilmaz, C; Sati, ZE; Altiparmakogullari, IStrategic partnerships between organizations aimed to be more efficient and effective in logistics function increase in numbers day by day. Partnerships based on integration of capabilities, resources and competencies, share of risks and costs to adopt conditions in a dynamic environment. Total Relationship Management (TRM) is accepted as best method to prevent failure and to overcome difficulties in a partnership. Total Relationship Management philosophy examines relationship between all elements in a business environment with a quality focus. The main purpose of this study focus on determining how to use Total Relationship Management approach in strategic logistics partnership managementItem Efficacy of Lacosamide Therapy in Focal Onset Refractory Epilepsy of Childhood: A Single Center ExperienceAksoy, HU; Yilmaz, C; Ayça, S; Atasever, AK; Polat, M; Öztürk, SObjective: Treatment of childhood refractory epilepsy is a challenge for clinicians. Lacosamide is a new generation antiepileptic drug which is being used for focal onset seizures of adults and children. Efficacy and safety of the drug for adults have been demonstrated in various studies. The aim of this retrospective cross-sectional study is to evaluate the efficacy and safety of lacosamide in childhood refractory focal seizures in our clinic. Methods: We examined the medical records of 14 patients treated with lacosamide in our clinic between January 2016 and January 2020 in terms of demographic, etiological, neuroimaging findings, responses to treatment, adverse effects and drug-drug interactions. We evaluated the patients as responders to treatment whose seizure frequency decreased >=%50 after 6 months of lacosamide treatment. Results: in 12 patiens (%85.7) seizure frequency decreased >=%50 (rho<0.001) while 5 of them (%35.7) was seizure free. Despite to the long term treatment one patient did not response to lacosamide treatment, and 1 patient's treatment stopped due to aggravation of seizure after initiation of lacosamide treatment. Clinical adverse effects were observed in 3 (%21.4) patients. Cardiac adverse effects or drug-drug interactions were not observed in any patient. Conclusion: As a result of our study, we think that lacosamide is an effective and reliable treatment option for refractory focal seizures of childhood similar to the results of the studies cited in the literature. We also think that further investigations are needed to evaluate its efficacy in focal and different type of seizures of childhood.Item Neurocognitive effects and electrophysiological findings in ADHD and self-limiting centrotemporal spike wave epilepsy (SeLECTS) - A prospective tertiary care studyOrak, SA; Bilaç,ö; Polat, M; Sobay, NS; Yalçin, AH; Korkmaz, R; Kubur,ÇÇ; Atasever, AK; Yilmaz, C; Özyurt, BCObjective: The study aimed to determine the prevalence of attention deficit hyperactivity disorder (ADHD) in patients with self-limiting epilepsy with centrotemporal spike wave (SeLECTS), as well as the electroclinical features associated with this comorbid condition and the neurocognitive effects using psychometric tests. Additionally, we analysed the electrophysiological findings and neurocognitive status of patients with ADHD to estimate the prevalence of epilepsy and neurocognitive effects in the ADHD population and evaluate their clinical features. Method: The study included patients diagnosed with SeLECT and ADHD who were matched for age and gender. Electrophysiological tests, psychometric tests, demographic and clinical characteristics of SeLECTS patients aged 7-13 years and ADHD patients of similar age were analysed. The study examined electrophysiological and psychometric tests, as well as demographic and clinical characteristics. Both groups underwent testing using the Wechsler Intelligence Scale for Children (WISC-R), Stroop Colour and Word Test (SCWT), and EEG (Electroencephalogram). The SeLECT group also underwent the Bender Visual-Motor Gestalt Test. Rsults: No significant relationship was found between the SeLECT and ADHD groups in terms of age and gender. The rate of epileptiform discharge in EEG findings without a diagnosis of epilepsy was 5.6 % (n = 2) in the ADHD group. The rate of ADHD in the SeLECTS group was 28 % (n = 11). Although all subsections of the WISCR test were higher in the ADHD patient group than in the SeLECTS patient group, only verbal IQ and total IQ showed a significant difference. No significant differences were found between the completion times, error rates, and correction averages of the SCWT sections in both groups. There was no significant correlation found between the performance IQ, verbal IQ, and total intelligence scores in either the isolated SeLECTS patient group or the SeLECTS + ADHD patient group (p > 0.05). However, it is worth noting that verbal IQ was below normal in both groups and slightly lower in the SeLECT + ADHD group. Additionally, the mean SeWT completion time was significantly longer in the SeLECT + ADHD group than in the isolated SeLECT group. However, no significant difference was found in the Bender Gestalt Visual Motor Perception Test. In the psychometric analyses comparing the isolated SeLECTS, SeLECT + ADHD, and ADHD patient groups, the SCWT completion times were significantly longer in the SeLECT + ADHD group than in the other two groups. The verbal IQ score was significantly higher in the ADHD group than in the other two groups. Conclusion: In conclusion, although SeLECTS is commonly considered a benign form of epilepsy, our study found a high rate of comorbidity with ADHD. This condition has a negative impact on verbal intelligence and sustained attention, highlighting the importance of a complete neuropsychological evaluation at the stage of epilepsy diagnosis. It is crucial not to overlook the possibility of an ADHD diagnosis.Item Inflammatory Prognostic Index in Metastatic Renal Carcinoma Treated with NivolumabEkinci, F; Erdogan, AP; Yildirim, S; Bulut, G; Yilmaz, C; Barutca, SObjective: To evaluate the utility of inflammatory prognostic index (IPI), albumin, c-reactive protein (CRP), and lactate dehydrogenase (LDH) as predictive biomarkers of oncologic outcome in metastatic renal cell cancer (mRCC) patients treated with nivolumab. Methodology: Seventy-five mRCC patients treated with nivolumab between January 2017 and June 2020 were enrolled. Several factors were retrospectively investigated, including IPI, CRP, LDH, and albumin level, for their association with progression-free survival (PFS) and overall survival (OS). The IPI was calculated as CRP x NLR/albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors.Results: When analysed according to the calculated IPI score, it is seen that the group with <2.153 has an OS duration of 96.3 months, while the group with >= 2.153 has a shorter time of 42.9 months (p=0.02). In the analysis performed according to albumin level, it was reported that those with low levels (22.8 months) had worse median OS than those with high levels (92.8 months) (p=0.004). According to the cox regression analysis results, it was determined that those with a high IPI score significantly increased the risk of death compared to those with a low score (HR:2.4, p=0.023). However, this significance could not be confirmed in the multivariate analysis. It was analysed that those with low albumin levels significantly increased the risk of death compared to both Conclusion: Those with high IPI scores and low albumin levels were associated with worse median OS. However, only the multivariate analysis analysed albumin level as an independent prognostic variable. Prospective and more extensive research is needed to consolidate the potential prognostic power of these markers.Item Metastatic Pancreatic Cancer Second-Line Treatment Options: Is the Difference Only in Cost?Yildirim, S; Erdogan, AP; Karateke, M; Yilmaz, C; Özveren, A; Bulut, G; Ekinci, F; Almuradova, EIntroduction Although pancreatic cancer ranks seventh in cancer-related deaths, it is an extremely fatal disease, and more than 330,000 people die from this disease worldwide. Although there are many first-line treatment studies in the literature, there are almost no prospective studies regarding second-line therapy. Therefore, there is no standard approach in the second-line treatment of pancreatic cancer. We decided to conduct this study to investigate second-line treatments with problems such as cost, treatment efficacy, and toxicity. Methods Patients older than 18 years old who applied to Ege University Hospital medical oncology department with a diagnosis of metastatic pancreatic cancer, who received first-line chemotherapy due to their illness, and who had progressed afterwards were included in the study. The files of the patients who applied between 2013 and 2017 were examined. Results Our study's primary endpoint was progression-free survival, and it was found that the median progression-free survival was 3.2 months in the Xelox patients, 3.7 months in the gemcitabine-nab paclitaxel patients, and 3.5 months in the other regimens. When the secondary endpoint was evaluated, overall survival, the median overall survival was 5.9 months in the Xelox patients, 5.3 months in the gemcitabine-nab paclitaxel patients, and 4.8 months in the other regimens. Conclusion As a result, second-line treatments were compared, and no statistically significant difference was found between them. For this reason, the side effects of previously used drugs and the side effects of new drugs to be used, as well as their costs, should be evaluated when choosing a treatment.Item Coinheritance of novel mutations in NAGLU causing mucopolysaccharidosis type IIIB and in DDHD2 causing spastic paraplegia54 in a Turkish familyBilgic, DG; Celebi, HBG; Gumus, AA; Bilgic, A; Yazici, H; Ceylaner, S; Yilmaz, C; Polat, M; Sahin, MA; Dereli, F; Cam, FSMucopolysaccharidosis type IIIB (MPSIIIB) is one of the lysosomal storage diseases, clinically related to developmental delay in the early phase and loss of skills in the late phases of the disease. The disease is caused by homozygous mutations in the NAGLU gene. Spastic paraplegia54 (SPG54) is a neurodegenerative disorder caused by homozygous mutations in the DDHD2 gene. Clinical features are progressive spasticity and weakness in the lower limbs and corpus callosum agenesis. We report on two siblings in a consanguineous family, presenting both the clinical and molecular diagnoses of MPSIIIB and SPG54 with novel mutations by using whole exome sequencing (WES). This interesting finding shows that we should be aware of the importance of using WES for diagnosing rare diseases in consanguineous families. (C) 2020 Elsevier Ltd. All rights reserved.Item An important source of preanalytical error in medical laboratories: centrifugationSonmez, C; Gümüs, A; Senes, M; Aykal, G; Taneli, F; Aksungar, F; Avci, E; Coskun, C; Cinaroglu, I; Colak, A; Eker, P; Güçel, F; Hakligor, A; Inal, BB; Orhan, B; Yilmaz, CCentrifugation separates particles within the specimen according to their shape, dimensions, and density and basically can be defined as a separation method. The centrifuge is an essential device in medical laboratories to prepare the serum, plasma, and urine samples for analysis. It is basically an electric device composed of the stationary (motor) and the motile (rotor) part. The centrifugation depends on two main variables: relative centrifugal force (RCF) and centrifugation time. The physical impact separating the specimen into its components in the centrifuge known as RCF is expressed as the multiples of gravitational acceleration (xg). RPM, defined as the number of rotations of the centrifuge perminute, shows the speed of the centrifuge. RCF value can be calculated by using RPM, and the centrifuge radius. Because models and sizes of centrifuges vary considerably, the use of gravity (g) forces instead of RPM is suggested. The centrifuges can be classified according to their usage, speed, technical specifications, and rotor type. An accurate and precise centrifugation process is essential to prevent errors in the preanalytical phase. The purpose of this document is to ensure the standardization of a good, precise protocol for the centrifugation process among the medical laboratories.Item Effect of Nicotine on RANKL and OPG and Bone Mineral DensityMizrak, S; Turan, V; Inan, S; Uysal, A; Yilmaz, C; Ercan, GAim: The signaling pathway OPG/RANK/RANKL is a key in maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss. In this study, our aim was to assess the effects of long-term nicotine exposure on plasma RANKL and OPG levels, tissue RANKL and OPG immunoreactivities, and bone mineral density (BMD) scores in rats. Materials and Methods: Thirty-six Swiss Albino rats weighing 70 +/- 10 g were divided into three groups. While the controls (n = 12) were only given normal drinking water, for low-dose nicotine (LDN) group (n = 12) 0.4 mg/kg/day; for high-dose nicotine (HDN) group (n = 12), 6.0 mg/kg/day nicotine was added to drinkingwater for a year. At the end of 12th month, BMD scores were measured using an Xray absorptiometry and bone turnover was assessed by measuring plasma RANKL and OPG levels and RANKL and OPG immunoreactivities in tail vertebrae of the rats. Results: There was no statistically significant difference in BMD scores of lumbar spine and femoral regions of the nicotine groups in comparison to controls. Plasma OPG levels were found to be significantly higher in HDN group, in comparison to the controls and LDN groups (p = .001) unlike plasma RANKL levels. Tissue RANKL and OPG immunoreactivities decreased significantly in the LDN and HDN groups (p < .001, p < .01, respectively). Conclusions: The results of this study show that nicotine is not primarily responsible for the decrease in BMD frequently seen in smokers. Measuring plasma RANKL and OPG levels did not reflect tissue immunoreactivities.