Gülhan Orekici Temel

Intravitreal bevacizumab effects on VEGF levels in distant organs: an experimental study

Abstract Purpose: The aim of this study was to determine the effects of single-dose intravitreal bevacizumab on the levels of vascular endothelial growth factor (VEGF) in serum and distant organs. Methods: Adult New Zealand albino rabbits (n = 40) were divided into experimental and control groups. Experimental rabbits received a single 0.05 ml intravitreal injection of 1.25 mg bevacizumab (Avastin) into the right eye, and control rabbits (n = 8) received no injection. Following injection, group 1 rabbits (n = 8) were sacrificed on day 1, group 2 rabbits (n = 8) on day 7, group 3 rabbits (n = 8) on day 14, and group 4 rabbits (n = 8) on day 28; control rabbits were sacrificed on day 28. After sacrifice, samples of brain, heart, liver, kidney and blood were collected. Levels of VEGF in serum and tissue were measured using enzyme-linked immunosorbent assay. The presence of bevacizumab was evaluated by immunofluorescence staining in tissues. Results: Positive bevacizumab immunoreactivity was observed in brain, heart and kidney. Serum VEGF levels significantly decreased in groups 3 and 4 compared with controls (p < 0.05). Liver VEGF levels significantly decreased in group 3 compared with controls (p < 0.05). Conclusions: Intravitreal bevacizumab not only may escape from the blood-retinal barrier and enter the general circulation, but also may be disseminated to distant organs. Our study demonstrates that a single dose of intravitreally injected bevacizumab decreases VEGF levels in serum and liver.

Gender differences in older adults with chronic migraine in Turkey

Chronic migraine is a growing and disabling subtype of migraine with different risk factors and clinical features, even in older adults. We sought to define and differentiate clinical features of chronic migraine in older adults. We also aimed to compare major clinical features of chronic migraine in older adults with those in younger people of both sexes.

Primary headaches in pediatric patients with chronic rheumatic disease

OBJECTIVES To assess the presence, prevalence and clinical characteristics of primary headaches in pediatric patients with chronic rheumatic diseases such as juvenile idiopathic arthritis (JIA) and familial Mediterranean fever (FMF), and to analyze the common pathophysiological mechanisms. STUDY DESIGN In this noncontrolled, cross-sectional study, a semi-structured 53 item headache questionnaire was administered to subjects with FMF and JIA, and interviewed a total sample size of 601 patients younger than16years of age. The questionnaires were then analyzed according to the International Headache Societys diagnostic criteria. RESULTS Children with FMF (n=378) and JIA (n=223) were studied. Each group was then divided into two subgroups according to whether the subjects reported headache or not. 29.5% of subjects with FMF reported having migraine, 37.6% probable migraine and 32.9% tension type headache (TTH). In JIA group 28.2% were diagnosed with migraine; 41.2% with probable migraine and 30.6% with TTH. No significant difference was found between all subjects with (n=258) and without (n=343) headache for variables such as living in a crowded family (p=0.95), being the first child in the family (p=0.63), academic achievement of the child (p=0.63), high education level (higher than high school) of the mother (p=0.52) and father (p=0.46). The presence of systemic disease was reported not to be effecting the daily life at the time of evaluation by 90.2% of the children with headache and 91.0% of the children without headache (p=0.94). 81.4% of the children reported their headaches were not aggravating with the exacerbation periods of their systemic disease. Family history of hypertension was reported higher by the subjects with headache (13.5% with headache and 4.0% without headache p=0.001). Diabetes mellitus was also reported higher (5.8% with headache; 0.5% without headache; p=0.006). Family history of headache was reported in 28.2% of the patients with headache whereas it was 17.4% of the patients without headache (p<0.001). Family history of headache was reported in 28.2% of the FMF subjects with headache whereas it was 17.4% of the patients without headache (p<0.001). For JIA patients a positive family history for headache was obtained in 25.9% of children with headache notably in migraineurs (81.8%). CONCLUSION Patients with JIA and FMF should be asked specifically about accompanying primary headaches particularly migraine headaches as they may be additional disabilities for these patients.

Affected States Soft Independent Modeling by Class Analogy from the Relation Between Independent Variables, Number of Independent Variables and Sample Size

OBJECTIVE The aim of study is to introduce method of Soft Independent Modeling of Class Analogy (SIMCA), and to express whether the method is affected from the number of independent variables, the relationship between variables and sample size. STUDY DESIGN Simulation study. MATERIAL AND METHODS SIMCA model is performed in two stages. In order to determine whether the method is influenced by the number of independent variables, the relationship between variables and sample size, simulations were done. Conditions in which sample sizes in both groups are equal, and where there are 30, 100 and 1000 samples; where the number of variables is 2, 3, 5, 10, 50 and 100; moreover where the relationship between variables are quite high, in medium level and quite low were mentioned. RESULTS Average classification accuracy of simulation results which were carried out 1000 times for each possible condition of trial plan were given as tables. CONCLUSION It is seen that diagnostic accuracy results increase as the number of independent variables increase. SIMCA method is a method in which the relationship between variables are quite high, the number of independent variables are many in number and where there are outlier values in the data that can be used in conditions having outlier values.

Determination of NF-κB and RANKL levels in peripheral blood osteoclast precursor cells in chronic kidney disease patients

PurposeChronic kidney disease (CKD) is a progressive condition characterized by irreversible loss of functional nephron mass due to variety of causes; an inevitable complication of CKD is metabolic bone disease, and this pathology is called as renal osteodystrophy (ROD). In this study, we aimed to determine the levels of serum sRANKL and intracellular NF-κB levels in peripheral blood osteoclast precursor cells in patients with stage 3 CKD.Materials and methodsForty-one male patients aged 35–60 with CKD identified as stage 3 according to GFR calculated on the basis of creatinine values and 27 healthy male subjects with age ranging from 40 to 60 as control group were included in this study. Levels of biochemical parameters, vitamin D3, parathyroid hormone, bone mineral density, sRANKL and NF-κB were determined by using photometric, electrochemiluminescence, HPLC, ELISA and flow cytometric methods in control and patient groups, respectively.ResultsWhen stage 3 CKD patients were compared with controls, patients with stage 3 CKD had statistically significantly higher iPTH levels, but they had statistically significantly lower vitamin D3 levels. However, the other biochemical parameters, bone mineral density, sRANKL and NF-κB levels did not reveal any significance.ConclusionIn conclusion, vitamin D3 and iPTH levels seem to be important parameters for evaluating the early stages of ROD. The lack of statistically significant differences in the levels of sRANKL and NF-κB suggests that these parameters are not sufficient in the evaluation of bone metabolism in the early stages of renal failure.

Awareness of Pleiotropic and Cardioprotective Effect of Statins in Patients with Coronary Artery Disease

Background Statins are commonly used in the secondary prevention of coronary artery disease. Studies have shown that the rate of statin use is low among patients with coronary artery disease. In this study, we aimed to investigate the reasons for poor patient compliance with statin treatment. Methods A total of 504 patients diagnosed with coronary heart disease were included in the study. Patients were asked 5 questions to assess their level of knowledge about statin therapy. Results Among the patients not using statins, 42% stated they did not take the medication because their cholesterol was not high or they did not know they should renew their prescription when they ran out and 35% because they were influenced by news reports in the media suggesting that cholesterol-lowering drugs were harmful. When patients who were aware of the pleiotropic/cardioprotective effects of statins were compared with patients who were not, the more knowledgeable patients had lower noncompliance rate and mean LDL-C level and a higher rate of LDL-C level optimization. Conclusion We found that patients who are aware of the pleiotropic effects of statins were more compliant with treatment. We believe that spending more time explaining and emphasizing the mechanisms of action, reason for prescribing, and necessary treatment duration of drugs that patients must use will result in greater compliance and improve patient care. In this way, patients may be less influenced by misinformation presented by the media.

GDF9 and BMP15 Expressions and Fine Structure Changes during Folliculogenesis in Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome is the most frequently seen endocrine disorder in women of reproductive age with a prevalence of about 10%. Aims: To investigate the efficiency of growth differentiation factor 9 and bone morphogenetic protein 15 during folliculogenesis in a dehydroepiandrosterone-induced mouse Polycystic ovary syndrome model. Study Design: Animal experimentation. Methods: Mice were divided into 3 groups: control, vehicle and Polycystic ovary syndrome. Polycystic ovary syndrome model mice were developed by the injection of dehydroepiandrosterone dissolved in 0.1 mL of sesame oil. Ovarian tissues were examined for growth differentiation factor 9 and bone morphogenetic protein 15 using immunofluorescent labelling and electron microscopic examinations. Results: The immunoreactivity of growth differentiation factor 9 and bone morphogenetic protein 15 proteins decreased (p<0.05) in the Polycystic ovary syndrome group (27.73±8.43 and 24.85±7.03, respectively) compared with the control group (33.72±11.22 and 31.12±11.05, respectively) and vehicle group (33.95±10.75 and 29.99±10.72, respectively). Apoptotic changes were observed in granulosa cells, lipid vacuoles increased in Theca cells and thickening and irregularities were noted in the basal lamina of granulosa cells. An increased electron density in the zona pellucida in some of the multilaminar primary and secondary follicles in the Polycystic ovary syndrome model was also observed at the ultrastructural level. Conclusion: These results suggest that the decrease in the growth differentiation factor 9 and bone morphogenetic protein 15 expression initiated at the primary follicle stage effect the follicle development and zona pellucida structure and may cause subfertility or infertility in Polycystic ovary syndrome.

Cranial Autonomic Features in Migraine and Migrainous Features in Cluster Headache

Introduction Limited data about the importance of cranial autonomic features of migraines and migrainous features of cluster headaches are available. Methods We enrolled 2955 patients with migraine and 93 patients with cluster headache. We explored the autonomic features, including ptosis, lacrimation, rhinorrhea, facial swelling, conjunctival injection, and pupil changes. The presence of migrainous features, such as nausea, vomiting, photophobia, and phonophobia, in cluster headache patients were noted. Results Migraine patients with underlying autonomic symptoms (MwuAS) and those without differed significantly. Unilaterality, periocular localization of headaches provoked by starvation, and history of abdominal pain significantly increased the risk of MwuAS. The parameters with the highest sensitivity (94.38%) and specificity (99.89%) for the diagnosis of MwuAS were lacrimation, facial swelling, and conjunctival injection. Conclusion Migraine and cluster headache are considered two different entities with different pathophysiologies. The assessment of autonomic symptoms is essential, and specialists must consider such an overlap in clinical practice in order to obtain accurate prevalence rates. In particular, lacrimation, conjunctival injection, and facial swelling are widely experienced by migraineurs.

An Alternative Method Used in Evaluating Agreement among Repeat Measurements by Two Raters in Education

Criteria regarding whether a concept, theory, design, or even a whole discipline is actually scientific vary from one field to another. However, there are invariant criteria for all fields such as the abilities to observe, measure, transmit, repeat, reproduce, verify, and falsify. These criteria allow different scientists to monitor or determine whether theories or designs related to a specific case or concept are valid and reliable. These criteria even prepare the conditions for measurability and reproducibility, which allow the opportunity for further research, as well as protect scientists from being trapped in prejudices. One of the essential criteria for science is measurability. Hence, advances in science can be claimed to develop in parallel with advances in measurement science (Erdogan, 2011; Karakac, 1988).In this respect, one can argue that compared to other science disciplines, advances in scientific fields where the investigated qualities can be directly measured are quicker, and therefore, quality measurements are comparatively easier to undertake.The situation is completely different in science disciplines such as education and psychology where the investigated qualities cannot be directly measured. In these disciplines, one attempts to predict the conditions of the related quality based on responses provided to specific stimuli; in other words, measurement is indirect (Gulliksen, 1950). However, although indirect measurement makes it possible to measure qualities that cannot be directly measured, it may also radically increase the potential error sources involved in the process. While the direction and amount of these error sources are sometimes apparent and can be identified (i.e., fixed, systematic change), sometimes they cannot (random error). This fact makes it rather hard and complex to undertake quality measurement in sciences where indirect measurement is a necessity because error sources with unidentified directions and amounts damage data reliability and impair the accuracy of the procedural comparisons that use these measurements.Scientists have developed various methods and techniques for examining reliability related to different error sources. Although these methods and techniques can be found under different classifications in different resources, they are simply classified by Crocker and Algina (1986) as methods based on multiple applications (such as equivalent forms and test-retest methods) or single application (split-half method or item-covariance-based methods). As the classification shows, some methods and techniques calculate error sources by using a single application to examine data reliability, whereas others rely on repeated measures, or scoring by multiple raters.In scientific disciplines such as education and psychology, where the investigated qualities cannot be directly measured, written, oral, and kinetic exams that require scoring by more than one rater; procedural comparisons that compare new methods and techniques developed according to scientific and technological advances; longitudinal studies; scale adaptation-development studies; and so on, are common. Reliability is the weakest link in studies where it is necessary to collect data from the same variable using different measurement tools, or to collect data from the same variable by using the same tool at different intervals (Guler & Gelbal, 2010). As a matter of fact, taking more than one measurement from the same variable also hosts the possibility of contamination from error sources as a result of interaction, both singly and in combination. Therefore, although the internal consistency of scores received from measurement tools is examined in itself, it is necessary to ensure interrater and intra-rater agreement in order to provide reliability (Guler & Gelbal, 2010; Lin, Hedayet, & Wu, 2012). In this context, agreement means similarities among measurements obtained by different inter-raters/methods. …

Turkish adaptation of the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) for clinical investigators

Öz Purpose: The primary purpose in this study is to provide to researchers with the Turkish adaptation of GRRAS, which was initially developed for the sake of accurately and completely report reliability and agreement studies. The secondary purpose is to set forth the rate at which GRRAS was utilized in the reliability and agreement related articles published in the scanned journals of the Turkish Medical Index since 2011. Material and Methods: GRRAS was translated into Turkish by two authors. Later on, studies published in the Turkish Medical Index since 2011 were examined in line with the determined criteria. Results: The items included in each section of the Turkish-adapted GRASS were explained. Furthermore, in consequence of the scanning of the Turkish Medical Index, it was determined that of the total 34 studies were published. All these studies were evaluated with the use of the Turkish-adaption of GRRAS and on the basis of every item included in the guide, reporting percentages were determined by years and in total. Discussion and Conclusion: It was so important for reviewers and editors to make reviews in a standardized way and also for researchers to report their studies in a standard format. Amaç: Bu çalışmada birincil amaç, güvenilirlik ve uyum çalışmalarının doğru ve tam olarak raporlanabilmesi için geliştirilmiş olan GRRAS kılavuzunun Türkçeye uyarlanmış halini araştırmacılara sunmaktır. İkincil amaç olarak, 2011 yılından itibaren Türk Tıp Dizininde taranan dergilerde yayınlanan güvenilirlik ve uyum ile ilgili makalelerde GRRAS kılavuzundan ne kadar yararlanıldığını ortaya koymaktır. Gereç ve Yöntem: İki yazar tarafından GRRAS kılavuzu Türkçeye çevrilmiştir. 2011 yılından itibaren Türk Tıp Dizininde yayınlanmış olan çalışmalar belirlenen kriterler doğrultusunda incelenmiştir. Bulgular: Türkçeye uyarlanmış olan GRRAS kılavuzunun her bir bölümünde yer alan maddeler açıklanmıştır. Ayrıca, Türk Tıp Dizininde yapılan tarama sonucunda 34 çalışmanın yayınlanmış olduğu belirlenmiştir. Tüm bu çalışmalar, Türkçe uyarlaması yapılmış GRRAS kılavuzu kullanılarak değerlendirilmiş ve kılavuzda bulunan her bir madde için yıllara ve toplama göre rapor edilme yüzdeleri verilmiştir. Sonuç: Dergi hakem ve editörlerinin makale değerlendirme sürecinde standart bir şekilde değerlendirme yapabilmeleri, ayrıca araştırmacıların da yaptıkları çalışmaları, standart bir formatta raporlayabilmeleri açısından oldukça önemli bir nitelik taşımaktadır.Amac: Bu calismada birincil amac, guvenilirlik ve uyum calismalarinin dogru ve tam olarak raporlanabilmesi icin gelistirilmis olan GRRAS kilavuzunun Turkceye uyarlanmis halini arastirmacilara sunmaktir. Ikincil amac olarak, 2011 yilindan itibaren Turk Tip Dizininde taranan dergilerde yayinlanan guvenilirlik ve uyum ile ilgili makalelerde GRRAS kilavuzundan ne kadar yararlanildigini ortaya koymaktir. Gerec ve Yontem: Iki yazar tarafindan GRRAS kilavuzu Turkceye cevrilmistir. 2011 yilindan itibaren Turk Tip Dizininde yayinlanmis olan calismalar belirlenen kriterler dogrultusunda incelenmistir. Bulgular: Turkceye uyarlanmis olan GRRAS kilavuzunun her bir bolumunde yer alan maddeler aciklanmistir. Ayrica, Turk Tip Dizininde yapilan tarama sonucunda 34 calismanin yayinlanmis oldugu belirlenmistir. Tum bu calismalar, Turkce uyarlamasi yapilmis GRRAS kilavuzu kullanilarak degerlendirilmis ve kilavuzda bulunan her bir madde icin yillara ve toplama gore rapor edilme yuzdeleri verilmistir. Sonuc: Dergi hakem ve editorlerinin makale degerlendirme surecinde standart bir sekilde degerlendirme yapabilmeleri, ayrica arastirmacilarin da yaptiklari calismalari, standart bir formatta raporlayabilmeleri acisindan oldukca onemli bir nitelik tasimaktadir