Publications (30)53.54 Total impact
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Article: Assessment of atherosclerosis risk due to the homocysteine-asymmetric dimethylarginine-nitric oxide cascade in children taking antiepileptic drugs.
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ABSTRACT: PURPOSE: The aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, "hyperhomocysteinemia (HHcy)→asymmetric dimethylarginine (ADMA) increase→nitric oxide (NO) decrease", which is thought to contribute to the developmental process of atherosclerosis. METHODS: The participants included 53 epilepsy patients who received either valproic acid (VPA, n=26) or oxcarbazepine (OXC, n=27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured. RESULTS: The differences in Hcy, ADMA, NO, vitamin B(12) and folate levels between VPA, OXC and control groups were all insignificant (p>0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p<0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p>0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r=+0.276, p<0.05). CONCLUSION: HHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.Seizure 12/2012; · 1.80 Impact Factor -
Article: Retinal thickness in pediatric multiple sclerosis.
Journal of child neurology 12/2012; 27(12):1621-2. · 1.59 Impact Factor -
Article: Reduced Retinal Nerve Fiber Layer Thickness and Macular Volume in Pediatric Multiple Sclerosis.
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ABSTRACT: Retinal atrophy is well known in adult-onset multiple sclerosis but remains unexplored in children. We aimed to determine retinal nerve fiber layer thickness and macular volume in pediatric patients, with and without optic neuritis and their relations with visual evoked potentials. We also examined macular volume changes at month 12. Retinal nerve fiber layer thickness of all quadrants and macular volume were measured in 28 relapsing remitting multiple sclerosis eyes and 30 control eyes using optical coherence tomography and were found reduced in patients compared with controls. This reduction was more prominent in eyes with longer time interval from optic neuritis. Retinal nerve fiber thickness was lower in eyes with delayed visual evoked potentials. Visual evoked potential amplitudes were reduced in affected eyes compared to patients without optic neuritis. Macular volume reduced nonsignificantly in patients at month 12. Retinal atrophy occurs in pediatric multiple sclerosis, and previous optic neuritis accelerates this atrophy.Journal of child neurology 06/2012; · 1.59 Impact Factor -
Article: The effects of oxcarbazepine and valproate therapies on growth in children with epilepsy.
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ABSTRACT: Aim. This study aimed to evaluate the effects of monotherapy with valproate or oxcarbazepine on the linear growth of children with idiopathic epilepsy. Methods. Antiepileptic treatment with valproate or oxcarbazepine was initiated in 76 patients. These were evaluated at baseline and at 6 and 18 months after commencement of therapy to determine height standard deviations (height z-scores). Serum ghrelin, insulin-like growth factor-1, and insulin-like growth factor-binding protein-3 levels were measured. Results. In prepubertal patients receiving oxcarbazepine, height z-scores were elevated after 6 and 18 months of therapy (p = 0.008 and p = 0.001, respectively); in pubertal patients, a significant increase was noted at the 18th month of therapy (p = 0.004). In prepubertal patients receiving oxcarbazepine, serum standardized insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels were significantly higher at the 18th month of therapy compared with baseline (p = 0.005 and p = 0.004, respectively). In puber-tal patients receiving valproate, serum ghrelin levels were significantly decreased at the 18th month of therapy compared with baseline (p = 0.006). Conclusion. Exposure to oxcarbazepine stimulated linear growth in epileptic patients through mechanisms involving the release of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. In contrast, expo-sure to valproate did not affect linear growth, but did lead to a decrease in serum ghrelin levels.Endocrine Research 05/2012; 37(4):163-74. · 0.97 Impact Factor -
Article: Serum insulin, cortisol, leptin, neuropeptide Y, galanin and ghrelin levels in epileptic children receiving oxcarbazepine.
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ABSTRACT: The aim of this study was to investigate whether oxcarbazepine (OXC) monotherapy causes weight gain in epileptic children. A total of 22 children with epilepsy (age 3.0-16.4 years) were assigned to OXC therapy. Serum levels of glucose, insulin, cortisol, leptin, neuropeptide Y (NPY), galanin and ghrelin were assessed before OXC therapy (month 0) and after the 6th and 18th months. There was no statistically significant difference in weight-standard deviation score (SDS), Height-SDS, BMI-SDS, serum glucose, insulin, cortisol, leptin, NPY, galanin and ghrelin levels between initial values (month 0) and those in the 6th and 18th months after OXC therapy (p > 0.05). Our results indicate that OXC therapy causes neither weight change nor alterations in serum glucose, insulin, cortisol, leptin, NPY, galanin and ghrelin levels in children with epilepsy.European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 06/2011; 15(6):527-31. · 2.01 Impact Factor -
Article: Serum insulin, cortisol, leptin, neuropeptide Y, galanin and ghrelin levels in epileptic children receiving valproate.
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ABSTRACT: The objective of this study was to investigate the cause of valproate (VPA)-associated weight gain in children. Eighteen children (10.94 ± 3.78 years) with epilepsy were assigned to VPA therapy. Serum levels of glucose, insulin, cortisol, leptin, neuropeptide Y (NPY), galanin and ghrelin were assessed before (month 0) and after 18 months of therapy. Eighteen age- and gender-matched patients (10.78 ± 3.95 years) were enrolled as the control group. Excess per capita weight of 2.3 kg was determined in the children receiving VPA over 18 months compared to the control group. In these patients, a statistically significant increase in standardized weight score, Homeostasis Model Assessment index, serum leptin, NPY and galanin values was determined at the 18th month compared to those before VPA treatment and in the control group, and there was also a significant decrease in ghrelin values. Increased serum levels of leptin, NPY and galanin play an important role in VPA-associated weight gain in children. While ghrelin is not directly associated with weight gain, its serum levels decline as a response to weight gain.Hormone Research in Paediatrics 06/2011; 76(1):65-71. -
Article: Effects of epilepsy and antiepileptic drugs on nitric oxide, lipid peroxidation and xanthine oxidase system in children with idiopathic epilepsy.
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ABSTRACT: The aim of this study is to investigate the effects of epilepsy, valproic acid and oxcarbazepine on nitric oxide levels, lipid peroxidation and xanthine oxidase levels in newly diagnosed epileptic children and healthy controls. A total of 49 patients with newly diagnosed idiopathic epilepsy and 15 healthy children were enrolled in this study. Of these 49 patients, 16 children were treated with valproate and 16 treated with oxcarbazepine. Nitric oxide, malondialdehyde and xanthine oxidase levels prior to antiepileptic drug therapy were measured in the serum. Blood samples were drawn before antiepileptic drug therapy and after 3 and 6 months of the antiepileptic drug treatment. Nitric oxide levels were statistically higher in the newly diagnosed epileptic patients. In oxcarbazepine group, the nitric oxide and malondialdehyde levels were found to be decreased. No statistically significant differences were noted in nitric oxide, malondialdehyde and xanthine oxidase levels in valproic acid treated group. Oxcarbazepine which is a frequently used new antiepileptic drug in childhood epilepsy may modify nitric oxide levels and lipid peroxidation. These results suggest that decreased lipid peroxidation would play a role in the mechanism of antiepileptic effects by oxcarbazepine treatment.Seizure 03/2011; 20(2):138-42. · 1.80 Impact Factor -
Article: Relapsing acute disseminated encephalomyelitis in children: further evaluation of the diagnosis.
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ABSTRACT: We examined our cases of relapsing acute disseminated encephalomyelitis (n = 13) in which diagnosis was made before the publication of the International Pediatric Multiple Sclerosis Study Group criteria in 2007, with the aim of reevaluating the primary diagnosis, examining any features indicative of other disorders, and determining the final diagnosis. Mean duration of follow-up was 9.4 (range, 2-20) years. Most (n = 11) were multiphasic, and 2 were recurrent cases. The final diagnosis changed in only 2 patients, both in the multiphasic group: one multiple sclerosis, and one other possible central nervous system vasculitis. All others are still being followed up as relapsing acute disseminated encephalomyelitis and had no further attacks. Six patients in this category did not have encephalopathy at first episode, which suggested the requirement for encephalopathy might be restrictive for certain cases. These results suggest the diagnosis of relapsing acute disseminated encephalomyelitis can be made correctly in most cases by clinical and imaging features.Journal of child neurology 12/2010; 25(12):1491-7. · 1.59 Impact Factor -
Article: Methylphenidate has dose-dependent negative effects on rat spermatogenesis: decreased round spermatids and testicular weight and increased p53 expression and apoptosis.
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ABSTRACT: In the present study, we aimed to evaluate the possible effects of methylphenidate on rat testes. Forty-two Wistar rats were randomly distributed into three experimental groups of 14 rats each. For 90 days, each group via gavage received the following: group 1 = tap water (control group), group 2 = 5 mg/kg/day of ritalin (methylphenidate, MPH), and group 3 = 10 mg/kg/day of ritalin. After sacrificing the animals, the body weights as well as the absolute and relative testicular weights were measured. Testes were sampled, fixed, and processed and, by histopathological examination, quantitative morphometric analysis of Sertoli cells, spermatocytes, and spermatids was performed in stages II, V, and XII. Immunohistochemistry was performed for transforming growth factor (TGF)-β1 and p53, and the apoptotic index was assessed through the TUNEL method. Group 2 had a reduction of round spermatids in stage II. Group 3 had reduction in both stage II and stage V spermatids, as well as lower testicular weight. The p53 expression was increased in group 3. In groups 2 and 3, the TGF-β1 expression was reduced and the apoptotic index by TUNEL was increased. Body weights remained stable on either group. Our results showed that methylphenidate might negatively affect spermatogenesis not only by reducing testicular weight and amount of round spermatids but also by increasing apoptotic death and p53 activation. The findings of the study, however, must be cautiously interpreted.Human & Experimental Toxicology 12/2010; 30(10):1592-600. · 1.31 Impact Factor -
Article: Effects of chronic treatment with valproate and oxcarbazepine on testicular development in rats.
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ABSTRACT: The aim of this study was to examine the potential effects of valproate (VPA) and oxcarbazepine (OXC) on testicular development in rats. Forty-two Wistar rats were randomly divided into three groups of 14 rats each. Each group received the following via gavage over 90 days: group 1, tap water (control group); group 2, VPA (300mg/kg/day); group 3, OXC (100mg/kg/day). After sacrifice, body, testicular and epididymidis weights were measured. Testes were sampled, fixed and processed, and quantitative morphometric analysis of Sertoli cells, spermatocytes and spermatids was performed in stages II, V and XII by histopathological examination. Immunohistochemical staining was performed to transform growth factor beta 1 (TGF-β1) and p53, and the apoptotic index was assessed using the TUNEL method. Testis and relative testis weights were significantly lower in the VPA group compared to the control group (p<0.05). Spermatogonia, pachytene spermatocyte and round spermatocyte numbers decreased in all stages in both the VPA and OXC groups compared to the control group, though this was not statistically significant (p>0.05). Apoptotic cell counts and p53 immunoreaction were significantly high and TGF-β1 expression was significantly lower in the VPA group compared to that of the control group (p<0.05). In the OXC group, p53 immunoreaction and TGF-β1 expression decreased compared to the control group, but this difference did not attain statistical significance (p>0.05). Our results show that VPA treatment from prepuberty to adulthood significantly negatively affects spermatogenesis, not only by reducing testicular weight, but also by increasing apoptotic death and p53 and decreasing TGF-β1 activation. OXC has a minimal side effect on testicular development.Seizure 12/2010; 20(3):203-7. · 1.80 Impact Factor -
Article: Drug treatment failures and effectivity in children with newly diagnosed epilepsy.
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ABSTRACT: To determine the percentage of children whom first-line antiepileptic drug treatment failed and the specific reasons for the treatment failure in newly diagnosed epilepsy. Hospital records were reviewed for 225 children who were newly diagnosed with epilepsy, started on the first antiepileptic drug, and then monitored for approximately 4.2 years. Of the 225 patients analyzed, the mean age was 7.9 ± 0.6 years at diagnosis. Most of the patients suffered from primarily generalized tonic-clonic seizures (in 84 patients, 37.3%). 114 patients (50.6%) were classified as having idiopathic epilepsy, 64 (28.4%) had symptomatic epilepsy and 47 (20.8%) has cryptogenic epilepsy. Valproic acid (n: 120, 53.3%), carbamazepine (n: 45, 20%) and oxcarbazepine (n: 31, 13.7%) were the most frequently prescribed antiepileptic drugs. Overall, 67.5% (n: 152) patients were treated successfully with the first antiepileptic drug. Seventy-three patients failed with the first-line antiepileptic drug. Of these patients, 28 discontinued medication because of adverse effects (38.3%), 26 because of lack of efficacy (35.6%) and 19 (26.02%)because of a combination of inefficacy and adverse effects. Age at diagnosis, seizure, etiology and antiepileptic drug selection are considered to be associated with drug treatment failure in childhood epilepsy. There was no statistically significant effect of any of these variables on first-line treatment outcome. Approximately one-third of the children with newly diagnosed epilepsy fail the first prescribed antiepileptic drug. Adverse effects and lack of efficacy contributed equally to the treatment failures.Seizure 11/2010; 19(9):553-7. · 1.80 Impact Factor -
Article: Knowledge of, perception of, and attitudes toward epilepsy of schoolchildren in Ankara and the effect of an educational program.
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ABSTRACT: Epilepsy is one of the most common serious chronic brain disorders of childhood and carries a strong social stigma. It has been generally accepted that educational programs can be beneficial in reducing the stigma of a number of chronic diseases such as epilepsy. In this article, we describe the first Turkish survey of primary school students' knowledge of and attitudes toward epilepsy and the effect of an epilepsy education program on the understanding of epilepsy in schoolchildren attending three different upper-middle schools in the city of Ankara. The epilepsy education program was found to be associated with a significant increase in knowledge of and positive attitudes toward epilepsy. In addition, students at higher socioeconomic levels performed better on both pre- and posttests. This emphasizes the importance of an educational program and the need for continued information and support for education about epilepsy.Epilepsy & Behavior 11/2009; 17(1):56-63. · 2.34 Impact Factor -
Article: Prophylactic drugs and cytokine and leptin levels in children with migraine.
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ABSTRACT: The study objective was to evaluate levels of the cytokines tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 and of leptin, and then to determine the relationship between these levels and clinical responses in children with migraine after prophylactic therapy with one of four drugs. In all, 77 children who needed prophylactic drugs were treated with cyproheptadine, amitriptyline, propranolol, or flunarizine. Serum levels of the cytokines and leptin were measured before and 4 months after the treatment. Results were compared by drug for headache frequency, severity, and duration, the PedMIDAS score, and levels of each cytokine and of leptin. Each of the four drugs not only decreased the frequency and duration but also the severity of headache, and the PedMIDAS score. None of the drugs was found to be superior to others in terms of reduction in cytokine levels (P > 0.05). Both cyproheptadine and flunarizine (but not amitriptyline and propranolol) caused an increase in leptin levels (P < 0.05). These data suggest that cytokine levels are related to clinical responses, and might help in objective evaluation of clinical response in migraine. To our knowledge, the present study is the first trial to compare the effects of prophylactic drugs, cytokine levels, and leptin levels in children with migraine.Pediatric Neurology 10/2009; 41(4):281-7. · 1.52 Impact Factor -
Article: The efficacy of vagal nerve stimulation in children with pharmacoresistant epilepsy: practical experience at a Turkish tertiary referral center.
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ABSTRACT: Vagus nerve stimulation (VNS) is an effective therapy for pharmacoresistant epilepsy. Nevertheless, information regarding the long-term outcome of VNS in children is limited. To describe the long-term outcome of VNS in patients with pharmacoresistant epilepsy treated at the Gazi University Medical Faculty Epilepsy Center, Turkey. The study included 24 patients - all younger than 18 years of age (mean age: 14.31 years). Median age at the time of VNS device implantation was 11 years. Median age at onset of epilepsy was 21 months and median duration of epilepsy was 126 months. All the patients' seizures were intractable with antiepileptic drug treatment and all had been treated with an average of 6+/-2 antiepileptic medications. In all, 12 patients had secondary generalized seizures and 12 had partial seizures. Because this was a retrospective open study, the number of seizures could not be enumerated in most of these cases. The only factor that was associated with seizure reduction was duration of follow-up. Age at seizure onset and age at VNS device implantation were not associated with seizure reduction. The difference in seizure reduction between patients >12 years of age and patients <12 years of age was not significant. Mean percentage of seizure reduction after 6 months-7 years of treatment was, respectively, 22.5% (n=24) (6th month), 32% (n=20) (1st year), 42% (n=16) (2nd year), 50.45% (n=11) (3rd year), 52% (n=10) (4th year), 60% (n=8) (5th year), 61.25% (n=8) (6th year), and 61.6% (n=6) (7th year). The positive effect of VNS persisted throughout the follow-up period. Although it is an expensive method, VNS is an effective treatment method. This series shows the necessity of long-term follow-up series for understanding the efficacy and advantages of VNS. Prospective, long-term double-blind studies with large samples are needed to confirm the present study's findings.European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 10/2009; 14(4):334-9. · 2.01 Impact Factor -
Article: Assessment of mothers' knowledge and perceptions of electroencephalography and determination of the short-term effect of an informational leaflet.
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ABSTRACT: The goal of the study described here was to determine mothers' knowledge and perceptions of electroencephalogram (EEG), to assess mothers' understanding of the main aspects of electroencephalography (EEG), and to determine the effect of an informational leaflet on increasing knowledge and perception. A 20-item questionnaire was developed to assess mothers' knowledge and perceptions of EEG. The questionnaire comprised 20 simple statements on aspects of the procedure, to which the mothers answered "yes" or "no." Mothers were interviewed in person by an EEG technician at the beginning of the study. On completion of the questionnaire, the same technician provided the mothers with an informational leaflet. One month later, the mothers were telephoned and administered the same questionnaire over the phone. The response rate was 86%. Before reading the informational leaflet, 89.5% of the mothers stated that they knew why their child was undergoing electroencephalography, and 67.6% knew what electroencephalography was. Furthermore, 78.1% of them believed that their child's brain was mapped by electroencephalography. In addition, nearly 1 in 10 believed that EEG is a hazardous procedure and 6% believed it was addictive. Knowledge and perceptions changed after distribution of the informational leaflet. Comparison of mothers with different income levels, educational status, and numbers of electroencephalograms their child underwent revealed statistically significant differences with respect to knowledge and perceptions of electroencephalography. Written information is a simple, inexpensive, easy-to-implement, yet effective method of improving parental understanding of EEG. The present study has significant implications for informing individuals regarding medical procedures.Epilepsy & Behavior 09/2009; 15(4):491-5. · 2.34 Impact Factor -
Article: Histologic and morphologic effects of valproic acid and oxcarbazepine on rat uterine and ovarian cells.
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ABSTRACT: To determine the histologic and morphologic effects of valproic acid (VPA) and oxcarbazepine (OXC) on rat uterine and ovarian cells. Fifty-six female prepubertal Wistar rats (21-24 days old and weighing between 47.5 and 58.1 g) were divided equally into four groups, which were given drinking water (controls), 300 mg/kg/day of VPA, 100 mg/kg/day of OXC or VPA + OXC via gavage, for 90 days. Ovaries and uteri of rats on proestrous and diestrous phases of estrous cycle were extirpated and placed in a fixation solution. The tissue specimens were assessed with apoptosis (TUNEL) staining protocols, eosinophil counting, and electron microscopic techniques. In uteri, apoptosis in stroma, mitochondrial swelling, and cristolysis were observed in the VPA group, and OXC led to negative effects on epithelial cell and intracellular edema. In ovaries, both drugs increased apoptosis and intracytoplasmic edema. Organelle structure disruption was also observed in the OXC group. More conspicuous degenerative modifications were determined in the VPA + OXC group. In uteri, the number of TUNEL-positive luminal epithelial cells was 7.20 +/- 1.32 in controls, and significantly increased to 29.60 +/- 1.58, 34.20 +/- 2.53, and 54.80 +/- 2.04 in VPA, OXC, and VPA + OXC groups, respectively (p < 0.001). The highest number of TUNEL-positive glandular epithelium cells was observed in the VPA + OXC group; however, the number of TUNEL-positive stroma cells was highest in the VPA group. The highest number of eosinophils in stroma was in the VPA group. VPA and OXC trigger apoptotic and degenerative effects on rat uterine and ovarian cells. VPA also prevents implantation of embryo to the uterus and causes abortion via endometrial eosinophil infiltration.Epilepsia 09/2009; 51(1):98-107. · 3.96 Impact Factor -
Article: Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat.
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ABSTRACT: To evaluate and to compare the possible toxic effects of oxcarbazepine (OXC) and valproic acid (VPA) on retinal ganglion cells (RGCs) in rat. Forty female Wistar rats (21-24 days old and weighted between 44.6 and 57.3g) were divided equally into 4 experimental groups which were applied tap water (group 1), 300mg/(kgday) VPA (group 2), 100mg/(kgday) OXC (group 3), and both VPA and OXC (group 4) via gavage for 90 days. Enucleation was performed for histopathologic analysis. RGCs were counted under the light microscopic examination. RGC numbers in OXC and combined OXC-VPA groups were found to be lower than those of control group. On the other hand RGC number was comparable with those of control group in VPA group. OXC seems to be toxic to RGCs at 100mg/kg dose when it is been given as a monotherapy or combined with VPA. Single VPA treatment has no effect on RGC number.Seizure 04/2009; 18(6):396-9. · 1.80 Impact Factor -
Article: Tau and S100B proteins as biochemical markers of bilirubin-induced neurotoxicity in term neonates.
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ABSTRACT: We investigated the relationship between total serum bilirubin and serum Tau and S100B protein levels, and predicted a cutoff level of bilirubin-induced neurotoxicity in term newborns. Total serum bilirubin, serum Tau, and S100B levels were measured in 92 jaundiced term newborns. A neurologic examination, electroencephalogram, brainstem auditory-evoked response, and otoacoustic emission were performed in the infants on admission and at age 3 months. Serum Tau (r = 0.921, P < 0.001) and S100B (r = 0.927, P < 0.001) levels were correlated with total serum bilirubin levels in all infants. Serum Tau and S100B protein levels remained at a steady level up to a total serum bilirubin level of 19.1 mg/dL, and then demonstrated a significant increase. Mean total serum bilirubin, serum Tau, and S100B levels of infants who manifested auditory neuropathy, neurologic abnormalities, or electroencephalogram abnormalities were significantly higher than in infants without these abnormalities (P < 0.05). Clinical and laboratory findings of bilirubin-induced neurotoxicity developed after a total serum bilirubin level of 22 mg/dL was reached. Serum levels of Tau and S100B proteins in jaundiced term newborns were strongly correlated with early-phase bilirubin encephalopathy.Pediatric Neurology 10/2008; 39(4):245-52. · 1.52 Impact Factor -
Article: Attitudes of parents and physicians toward febrile seizures.
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ABSTRACT: Although febrile seizures are common in children, attitudes may change among parents. The management of a child may differ depending on the specialty of the attending physician. This study was carried out to analyze attitudes of Turkish parents and physicians toward febrile seizures. 308 children with febrile seizure who were admitted to the Department of Pediatric Neurology at Dr Sami Ulus Children's Hospital and Gazi University in Turkey between January 2006 and March 2007 were enrolled. Prior to seizure, approximately half of the parents took appropriate steps in reducing fever. The data also showed that there was a wide variation of treatment practice depending on the specialty of the attending physician. Educational level and economic status are important variables affecting attitudes of parents toward fever and febrile seizure. The management of the child with a febrile seizure differs even within the same specialty in Turkish physicians.Clinical Pediatrics 07/2008; 47(9):856-60. · 1.15 Impact Factor -
Article: Effects of chronic treatment with valproate and oxcarbazepine on ovarian folliculogenesis in rats.
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ABSTRACT: We aimed to define the morphologic effects of valproate (VPA) and oxcarbazepine (OXC) on ovarian folliculogenesis in rats. Forty female wistar rats (21-24 days old and weighted between 46.4 and 55.3 g) were divided equally into 4 experimental groups, which were applied tap water (control group), 300 mg/kg/day VPA, 100 mg/kg/day OXC, and both VPA and OXC via gavage for 90 days. Ovaries of the rats on proestrous and diesterous phase of estrous cycle according to daily vaginal smear were taken out and placed in a fixation solution. Immunohistochemical and apoptosis (TUNEL) staining protocols were applied. The number of follicles decreased and that of corpora lutea increased significantly in OXC, VPA, and OXC+VPA treated groups compared with control group (p < 0.05). The number of TUNEL positive ovarian follicles was 1.40 +/- 0.52 in control group, but it significantly increased to 3.50 +/- 0.53, 3.50 +/- 0.53, and 4.90 +/- 0.88 in VPA, OXC, and VPA+OXC groups (p < 0.0001). The increase in the number of TUNEL positive granulosa cells was also significant for OXC and VPA+OXC groups (p < 0.0001). Immunohistochemical HSCORE decreased for TGF beta 1 and IGF1 staining and increased for P53 staining in all drug groups compared with control group (p < 0.001). Intensity of P53 labeling increased, while intensity of TGF beta 1, IGF-1, and GDF-9 immunoreactivity decreased significantly in all drug groups compared with control group (p < 0.001). Long-term treatment with VPA or OXC from prepuberty to adulthood causes apoptosis and deterioration of folliculogenesis in rat ovarian follicles.Epilepsia 07/2008; 49(7):1192-201. · 3.96 Impact Factor
Top co-authors
Top Journals
Institutions
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2011–2012
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Karadeniz Technical University
- Faculty of Medicine
Trabzon, Trabzon, Turkey
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2002–2009
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Gazi University
- Faculty of Medicine
Ankara, Ankara, Turkey
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2005
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Hacettepe University
- Faculty of Medicine
Ankara, Ankara, Turkey -
Ankara Numune Training and Research Hospital
Ankara, Ankara, Turkey
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