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1. Expert opinion on the diagnostic odyssey and management of late-onset Pompe disease: a neurologist's perspective

Author

Sevim Erdem Ozdamar, Ayse Filiz Koc, Hacer Durmus Tekce, Dilcan Kotan, Ahmet Hakan Ekmekci, Ihsan Sukru Sengun, Ayse Nur Yuceyar, and Kayihan Uluc

Subjects
late-onset Pompe disease, diagnostic delay, diagnostic algorithm, index of suspicion, treatment, outcome, Neurology. Diseases of the nervous system, RC346-429
Abstract

This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the differential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns.

Published
2023
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2. Identifying a Cut-off Point for Timed Up and Go Test in Neuromuscular Diseases

Author

Cevher Savcun Demirci, Gülşah Sütçü, Fatma Ayvat, Özge Onursal Kılınç, Mert Doğan, Ender Ayvat, Can Ebru Bekircan-Kurt, Sevim Erdem-Özdamar, Sibel Aksu Yıldırım, Muhammed Kılınç, and Ersin Tan

Subjects
neuromuscular diseases, tug, cut-off value, falling, Medicine, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: Balance problems and falls due to a progressive loss of muscle strength in neuromuscular diseases (NMD) negatively affect the activities of daily living and functional independence of patients. The timed up and go (TUG) test is an easy-to-apply and objective measure of balance. This study aimed to determine the cut-off value of the TUG test in adult individuals with NMD. Materials and Methods: This retrospective study included 102 patients. The receiver operating characteristic analysis was performed and cut-off, sensitivity, and specificity values were calculated in NMD to determine the diagnostic validity of the TUG test. Results: The mean ages of 55 patients with a fall history and 47 patients without a fall history were 34.40+-10.41 and 31.87+-10.11 years, respectively. The mean values of the TUG scores of these individuals were calculated as 11.79+-4.30 and 7.33+-1.51 s, respectively. The cut-off value of the TUG test in adult individuals with the NMD was determined as 8.9 s. Conclusion: The present study revealed that individuals with NMD who complete the TUG test over 8.9 s have a high risk of falling. Determining the risk of falling in NMD, which is one of the neurological patient groups where falling complaints are most common, is extremely important for patient safety and the effectiveness of rehabilitation.

Published
2022
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3. Trigeminal sensory-motor neuropathy in a patient with mixed connective tissue disease and review of the literature

Author

Can Ebru Bekircan-Kurt, Çağrı Temuçin, Şule Apraş Bilgen, and Sevim Erdem-Ozdamar

Subjects
blink reflex, mixed connective tissue disease, trigeminal sensory–motor neuropathy, Neurology. Diseases of the nervous system, RC346-429
Abstract

Trigeminal neuropathy is an infrequent condition, usually limited to the sensorial component of the nerve, and it is one of the most common neurologic manifestations of mixed connective tissue disease (MCTD). However, to the best of our knowledge, no cases have been reported with MCTD presenting as trigeminal sensory and motor neuropathy. Herein, we report a 28-year-old female with unilateral trigeminal sensory–motor neuropathy who presented with numbness over the distribution of the right trigeminal region and right masseter atrophy. We also reviewed the literature for trigeminal neuropathy associated with MCTD.

Published
2020
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4. Comprehensive clinical, biochemical, radiological and genetic analysis of 28 Turkish cases with suspected metachromatic leukodystrophy and their relatives

Author

Faruk Pekgül, Nesibe Gevher Eroğlu-Ertuğrul, Can Ebru Bekircan-Kurt, Sevim Erdem-Ozdamar, Arda Çetinkaya, Ersin Tan, Bahadır Konuşkan, Ergun Karaağaoğlu, Meral Topçu, Nurten Ayşe Akarsu, Kader K. Oguz, Banu Anlar, and Hatice Asuman Özkara

Subjects
Metachromatic leukodystrophy, Multiple sulfatase deficiency, Arylsulfatase A, Urinary sulfatide, Antibody, MRI, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Metachromatic leukodystrophy (MLD) is a glycosphingolipid storage disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ASA) or its activator protein saposin B. MLD can affect all age groups in severity varying from a severe fatal form to milder adult onset forms. Diagnosis is usually made by measuring leukocyte ASA activity. However, this test can give false negative or false positive laboratory results due to pseudodeficiency of ASA and saposin B deficiency, respectively. Therefore, we aimed to evaluate patients with suspected MLD in a Turkish population by comprehensive clinical, biochemical, radiological, and genetic analyses for molecular and phenotypic characterization. We analyzed 28 suspected MLD patients and 41 relatives from 24 families. ASA activity was found to be decreased in 21 of 28 patients. Sixteen patients were diagnosed as MLD (11 late infantile, 2 juvenile and 3 adult types), 2 MSD, 2 pseudodeficiency (PD) and the remaining 8 patients were diagnosed as having other leukodystrophies. Enzyme analysis showed that the age of onset of MLD did not correlate with residual ASA activity. Sequence analysis showed 11 mutations in ARSA, of which 4 were novel (p.Trp195GlyfsTer5, p.Gly298Asp, p.Arg301Leu, and p.Gly311Asp), and 2 mutations in SUMF1 causing multiple sulfatase deficiency, and confirmed the diagnosis of MLD in 2 presymptomatic relatives. All individuals with confirmed mutations had low ASA activity and urinary sulfatide excretion. Intra- and inter-familial variability was high for the same ARSA missense genotypes, indicating the contribution of other factors to disease expression. Imaging findings were evaluated through a modified brain MRI scoring system which indicated patients with protein-truncating mutations had more severe MRI findings and late-infantile disease onset. MRI findings were not specific for the diagnosis. Anti-sulfatide IgM was similar to control subjects, and IgG, elevated in multiple sulfatase deficiency. In conclusion, the knowledge on the biochemical, clinical and genetic basis of MLD was expanded, a modified diagnostic laboratory algorithm for MLD based on integrated evaluation of ASA activity, urinary sulfatide excretion and genetic tests was devised.

Published
2020
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5. DİCLE NEHRİ VADİSİNDE AT VE BEYGİR CİNSİNİN ISLAHINA YÖNELİK KURULAN BİR ÇİFTLİK: HARNİNİ/KHARNİNİ ÇİFTLİĞİNİN İŞLEYİŞİ

Author

Sevim Erdem

Subjects
sultan ii. abdülhamid, harnini hayvan çiftliği, vi.ordu, remont bölüğü, History of the arts, NX440-632
Abstract

Sultan II. Abdülhamid kendi döneminde, ülke genelinde at ve beygir cinsinin ıslahı ve sayılarını artırmak, ordunun çeşitli sınıflarının ihtiyacını karşılamak, çiftlik sahiplerinin ve ziraat ile meşgul olanların kullanacağı hayvanları temin etmek ve bu konuda yabancı ülkelerden hayvan teminine ihtiyaç duymamak için “Hayvan Çiftlikleri” kurdurmuştur. Bu çiftliklerden bazıları özel olarak askeriyenin ihtiyacını karşılamaya yönelik olmuştur. Sultansuyu, Botan, Hamra, Veziriye, Harnini çiftlikleri örnek olarak verilebilir. Bu çiftlikler IV. V. ve VI. Ordunun Remont bölüklerinin at ve beygir ihtiyacını karşılamak amacıyla kurulmuştur.Bununla birlikte bu çiftliklerin bir özelliği de Dicle ve Fırat Nehri vadisinde yer almalarıdır. Sultan II. Abdülhamid Irak coğrafyasında devletin hâkimiyetini tesis etmek amacıyla buradaki arazileri bir yandan Hazine-i Hassa Nezareti çatısı altında toplarken diğer yanda da Dicle ve Fırat Nehri üzerindeki askeri kontrolü artırmaya çalışmıştır.Bu çalışmada Dicle Nehri vadisinde kurulan, Tikrit-Musul karayolu güzergahında ve aynı zamanda Şammar Aşiretinin temel yerleşim alanı içerisinde bulunan ve VI.Ordu Müşirliğine tahsis edilmiş olan Harnini/Kharnini çiftliği ele alınacaktır. Çalışma harita ve çizimlerle desteklenecektir.

Published
2018
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6. The altered expression of perineuronal net elements during neural differentiation

Author

Nazli F. Eskici, Sevim Erdem-Ozdamar, and Didem Dayangac-Erden

Subjects
Perineuronal nets, HAPLN1, Tenascin-R, Aggrecan, PC12 differentiation, Cytology, QH573-671
Abstract

Abstract Background Perineuronal nets (PNNs), which are localized around neurons during development, are specialized forms of neural extracellular matrix with neuroprotective and plasticity-regulating roles. Hyaluronan and proteoglycan link protein 1 (HAPLN1), tenascin-R (TNR) and aggrecan (ACAN) are key elements of PNNs. In diseases characterized by neuritogenesis defects, the expression of these proteins is known to be downregulated, suggesting that PNNs may have a role in neural differentiation. Methods In this study, the mRNA and protein levels of HAPLN1, TNR and ACAN were determined and compared at specific time points of neural differentiation. We used PC12 cells as the in vitro model because they reflect this developmental process. Results On day 7, the HAPLN1 mRNA level showed a 2.9-fold increase compared to the non-differentiated state. However, the cellular HAPLN1 protein level showed a decrease, indicating that the protein may have roles in neural differentiation, and may be secreted during the early period of differentiation. By contrast, TNR mRNA and protein levels remained unchanged, and the amount of cellular ACAN protein showed a 3.7-fold increase at day 7. These results suggest that ACAN may be secreted after day 7, possibly due to its large amount of post-translational modifications. Conclusions Our results provide preliminary data on the expression of PNN elements during neural differentiation. Further investigations will be performed on the role of these elements in neurological disease models.

Published
2018
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7. Dysferlinopathy: A Case Report and Literature Update

Author

Orkide Kutlu, Can Ebru Bekircan Kurt, İbrahim Ünsal, Zeynep Arıbaş, Bilge Renkliyıldız, Hasan Eruzun, Ayşe Duran Karagülmez, and Sevim Erdem Özdamar

Subjects
Dysferlinopathy, CK, polymyositis, Medicine
Abstract

Dysferlinopathy is a rare autosomal recessive myopathy, resulting in the lack or absence of dysferlin production caused by mutations in the encoding gene. Dysferlin is a sarcolemmal membrane protein involved in the repair of membrane damage caused by calcium. There are four identified phenotypic dysferlinopathies, two of which are relatively frequently observed. Miyoshi myopathy and limb-girdle muscular dystrophy type 2B are frequently observed; the two very rare dysferlinopathies are distal anterior compartment myopathy and scapuloperoneal muscular dystrophy (observed in only one case). Serum CK levels are quite high, even in the pre-clinical period. A muscle biopsy typically shows dystrophic patterns, often accompanied with T-lymphocyte-based inflammatory changes. The clinical course of dysferlinopathy is usually much better than that of other recessive trait muscular dystrophies. Dysferlinopathies should be considered in the differential diagnosis of polymyositis to avoid unnecessary and potentially dangerous medications such as oral steroids or immunosuppressive therapies. Here we report the case a 21-year-old Syrian patient diagnosed with dysferlinopathy who has had serious CK elevations from the age of 1 and who had been diagnosed with polymyositis by a muscle biopsy 7 years ago and who therefore used steroids/azathioprine for the following 3 years.

Published
2016
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8. The Neurophysiologic Frequency of Hereditary Neuropathy with Liability to Pressure Palsy in Entrapment Neuropathies

Author

F Gökçem Yıldız, Gülay Nurlu, Sevim Erdem Özdamar, and Çağrı Mesut Temuçin

Subjects
Hereditary neuropathy with liability to pressure palsy, entrapment neuropathy, peripheral myelin protein 22, Medicine, Neurology. Diseases of the nervous system, RC346-429
Abstract

Objective: Hereditary neuropathy with liability to pressure palsy (HNPP) needs to be differentiated from entrapment neuropathies due to differences in the treatment management. Materials and Methods: Among 5075 patients with entrapment neuropathy, we retrospectively evaluated the neurophysiologic results of 20 patients with three or more entrapments. Results: Ten patients were diagnosed as having HNPP according to their genetic or nerve biopsy results; eight (80%) had bilateral Carpal tunnel syndrome, nine (90%) had bilateral ulnar entrapment neuropathy, eight (80%) had bilateral median and ulnar entrapment together; and three (30%) had one-sided peroneal neuropathy. Conclusion: Our data suggest that analyzing the neurophysiologic studies and keeping HNPP in mind are essential to characterize underdiagnosed patients with HNPP referred for entrapment neuropathy.

Published
2016
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10. Early Diagnosis of Distal Peripheral Polyneuropathy Due to Glucose Metabolism Disorders via Intraepidermal Nerve Fiber Analysis

Author

Oğuzhan Kurşun, Hülya Karataş, Kayıhan Uluç, Sevim Erdem Özdamar, Tomris Erbaş, and Ersin Tan

Subjects
Diabetes mellitus, glucose intolerance, polyneuropathies, nerve fibers, skin, biopsy, Medicine, Neurology. Diseases of the nervous system, RC346-429
Abstract

OBJECTIVE: Polyneuropathy is the most frequent complication of diabetes mellitus (DM), which is a common disorder worldwide. Early diagnosis of this complication is critical for treatment planning. Recently, intra-epidermal nerve fiber (IENF) analysis has been used for the early diagnosis of diabetic neuropathy and was reported to be superior to both conventional fascicular nerve biopsy and other diagnostic tests. The present study aimed to determine the effect of early glucose metabolism disorders on the peripheral nerves using IENF analysis. METHODS: : This prospective study compared IENF nerve fiber density in 10 patients with early-stage DM and 12 patients with impaired glucose tolerance (IGT) to that of healthy controls in order to investigate fiber loss in the asymptomatic stage. RESULTS: Mean age of the DM and IGT groups was 53.4 ± 10.9 years and 50.8 ± 10.6 years, respectively. Neither the IGT nor DM patients had paresthesia. Neurological examination results of the patients were all in the normal range. Mean fiber density was 6.4 ± 2.7 mm-1 in the DM group, 7.5 ± 3.2 mm-1 in the IGT group, and 13.7 ± 2.7 mm-1 in the control group (p< 0.0001). Paired analysis of the groups showed a significant difference between the 2 patient groups and the control group. There was a statistically significant difference in mean nerve fiber density between the DM and control groups (p< 0.0001, Mann-Whitney U test), and between the IGT and control groups (p< 0.0001, Mann-Whitney U test); however, there wasn’t a significant difference between the DM and IGT groups (p= 0.5, Mann-Whitney U test). CONCLUSION: The results show that IENF density in the IGT and DM groups decreased in the asymptomatic stage of DM. This means that polyneuropathy can begin in the prediabetic period in patients with glucose metabolism disorders. This critical information highlighs the importance of the early diagnosis and treatment of glucose metabolism disorders in preventing neurological complications

Published
2009

12. A database for screening and registering late onset Pompe disease in Turkey

Author

Deymeer, Feza, Parman, Yesim, Kendirci, Murat, Sayan, Saadet, Celebi, Lale Gundogdu, Uluç, Kayıhan, Tanrıdağ, Tülin, Yuceyar, Nur, Ekmekci, Ozgul, Colakoglu, Beril Dönmez, Ozturk, Serefnur, Tireli, Hulya, Selcuki, Deniz, Neyal, Ayse Munife, Kayran, Yusuf, Aluclu, Mehmet Ufuk, Koyuncuoglu, Hasan Rifat, Tokucoglu, Figen, Secil, Yaprak, Guney, Figen, Gozke, Eren, Balaban, Hatice, Akalın, Mehmet Ali, Koc, Ayse Filiz, Mulayim, Serap, Turgut, Nilda, Gokyigit, Munevver Celik, Ekmekci, Hakan, Durmus, Hacer, Karlı, Necdet, Koseoglu, Emel, Aysal, Fikret, Kotan, Dilcan, Ali, Asuman, Koytak, Pınar Kahraman, Karasoy, Hatice, Yaman, Aylin, Sengun, İhsan Sukru, Sayin, Refah, Tiftikcioglu, Bedile Irem, Soysal, Aysun, Tutkavul, Kemal, Bayrak, Ayse Oytun, Kısabay, Aysin, Elci, Mehmet Ali, Yayla, Vildan, Yılmaz, İbrahim Arda, Ozdamar, Sevim Erdem, Erdogan, Cagdas, Tasdemir, Nebahat, and Serdaroglu Oflazer, Piraye

Published
2018
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13. Multimodal assessment of intensive care unit-acquired weakness in severe stroke patients

Author

Berin Inan, Can Ebru Bekircan-Kurt, Zeynep Ergul-Ulger, Merve Yilmaz, Zeliha Gunnur Dikmen, Ethem Murat Arsava, Mehmet Akif Topcuoglu, Omur Caglar, Merve Basol, Ergun Karaagaoglu, Sevim Erdem-Ozdamar, Ersin Tan, and Cagri Mesut Temucin

Subjects
Stroke, Intensive Care Units, Muscle Weakness, Humans, Neurology (clinical), General Medicine, Muscle, Skeletal
Abstract

Intensive care unit-acquired weakness (ICUAW) defines generalized muscle weakness seen in critically ill patients in the absence of other causative factors. Herein, we aimed to evaluate ICUAW in stroke patients by electrodiagnostic testing, histopathology, and assessment of respiratory complex activities (RCA), to define the frequency of ICUAW in this patient group, and to reach new parameters for early prediction and diagnosis.We prospectively recruited twenty-four severe acute stroke patients during a sixteen-month period. In addition to serial nerve conduction studies (NCS), we performed muscle biopsy and RCA analysis on the non-paretic side when ICUAW developed. Patients undergoing orthopedic surgery without metabolic and neuromuscular diseases constituted the control group for RCA. Survival and longitudinal data were analyzed by joint modeling to determine the relationship between electrophysiological parameters and ICUAW diagnosis.Eight patients (33%) developed ICUAW, and six of them within the first two weeks. Extensor digitorum brevis, abductor digiti minimi (ADM), rectus femoris and vastus medialis (VM) compound muscle action potential (CMAP) amplitudes showed a significant decrease in the ICUAW group. VM CMAP amplitude (BIC = 358.1574) and ADM CMAP duration (BIC = 361.1028) were the best-correlated parameters with ICUAW diagnosis. The most informative electrophysiological findings during the entire study were obtained within the first 11 days. Muscle biopsies revealed varying degrees of type 2 fiber atrophy. Complex I (p = 0.003) and IV (p = 0.018) activities decreased in patients with ICUAW compared to controls.VM CMAP amplitude and ADM CMAP duration correlate well with ICUAW diagnosis, and may aid in the early diagnosis.

Published
2022
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17. The functional and structural evaluation of small fibers in asymptomatic carriers of TTR p.Val50Met (Val30Met) mutation

Author

Can Ebru Bekircan-Kurt, Ezgi Yilmaz, Doruk Arslan, Fatma Gokcem Yildiz, Özlem Dikmetas, Zeynep Ergul-Ulger, Sibel Kocabeyoglu, Murat Irkec, Vedat Hekimsoy, Lale Tokgozoglu, Ersin Tan, and Sevim Erdem-Ozdamar

Subjects
Adult, Male, Neurologic Examination, Amyloid, Amyloid Neuropathies, Familial, Heterozygote, Adolescent, Biopsy, Neural Conduction, Middle Aged, Neurology, Mutation, Pediatrics, Perinatology and Child Health, Humans, Prealbumin, Female, Prospective Studies, Neurology (clinical), Genetics (clinical), Skin
Abstract

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients' family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

Published
2022
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18. Two distinct skeletal muscle microRNA signatures revealing the complex mechanism of sporadic ALS

Author

Ersin Tan, Can Ebru Bekircan-Kurt, Ayse Tulay Aydinoglu, Sevim Erdem-Ozdamar, Evrim Aksu-Menges, and Burcu Balci-Hayta

Subjects
Mechanism (biology), business.industry, Gene Expression Profiling, Amyotrophic Lateral Sclerosis, Skeletal muscle, Differentially expressed mirnas, General Medicine, Computational biology, medicine.disease, Fold change, MicroRNAs, Gene Ontology, medicine.anatomical_structure, Downregulation and upregulation, microRNA, Humans, Medicine, Neurology (clinical), Amyotrophic lateral sclerosis, Muscle, Skeletal, business, Gene
Abstract

Skeletal muscle pathology is thought to have an important role in the onset and/or progression of amyotrophic lateral sclerosis (ALS), which is a neurodegenerative disorder characterized by progressive muscle weakness. Since miRNAs are recognized as important regulatory factors of essential biological processes, we aimed to identify differentially expressed miRNAs in the skeletal muscle of sporadic ALS patients through the combination of molecular-omic technologies and bioinformatic tools. We analyzed the miRnome profiles of skeletal muscle biopsies acquired from ten sALS patients and five controls with Affymetrix GeneChip miRNA 4.0 Array. To find out differentially expressed miRNAs in patients, data were analyzed by The Institute for Genomic Research-Multi Experiment Viewer (MeV) and miRNAs whose expression difference were statistically significant were identified as candidates. The potential target genes of these miRNAs were predicted by miRWalk 2.0 and were functionally enriched by gene ontology (GO) analysis. The expression level of priority candidates was validated by quantitative real-time PCR (qRT-PCR) analysis. We identified ten differentially expressed miRNAs in patients with a fold change threshold ≥ 2.0, FDR = 0. We identified ten differentially expressed miRNAs in patients with a fold change threshold ≥ 2.0, FDR = 0. Nine out of the ten miRNAs were found to be related to top three enriched ALS-related terms. Based on the qRT-PCR validation of candidate miRNAs, patients were separated into two groups: those with upregulated miR-4429 and miR-1825 expression and those with downregulated miR-638 expression. The different muscle-specific miRNA profiles in sALS patients may indicate the involvement of etiologic heterogeneity, which may allow the development of novel therapeutic strategies.

Published
2021
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20. Expert opinion on the diagnostic odyssey and management of late-onset Pompe disease: a neurologist's perspective.

Author

Ozdamar, Sevim Erdem, Koc, Ayse Filiz, Tekce, Hacer Durmus, Kotan, Dilcan, Ekmekci, Ahmet Hakan, Sengun, Ihsan Sukru, Yuceyar, Ayse Nur, and Uluc, Kayihan

Subjects
DELAYED diagnosis, TISSUE analysis, RESPIRATORY insufficiency, GLYCOGEN storage disease type II, GENETIC mutation, ADRENAL insufficiency, PHYSICIANS
Abstract

This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the di erential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

Author

Mantegazza, R., Wolfe, G. I., Muppidi, S., Wiendl, H., Fujita, K. P., O'Brien, F. L., Booth, H. D. E., Howard, J. F., Claudio Gabriel Mazia, Miguel, Wilken, Fabio, Barroso, Juliet, Saba, Marcelo, Rugiero, Mariela, Bettini, Marcelo, Chaves, Gonzalo, Vidal, Alejandra Dalila Garcia, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Rudy, Mercelis, Délphine, Mahieu, Linda, Wagemaekers, Philip Van Damme, Annelies, Depreitere, Caroline, Schotte, Charlotte, Smetcoren, Olivier, Stevens, Sien Van Daele, Nicolas, Vandenbussche, Annelies, Vanhee, Sarah, Verjans, Jan, Vynckier, Ann, D'Hont, Petra, Tilkin, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David, Feder, Daniel, Ambrosio, Gabor Lovasamela César, Ana Paula Melo, Renata Martins Ribeiro, Rosana, Rocha, Bruno Bezerra Rosa, Thabata, Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Maria da Penha Ananias Morita, Erica Nogueira Coelho, Gabriel, Paiva, Marina, Pozo, Natalia, Prando, Debora Dada Martineli Torres, Cristiani Fernanda Butinhao, Gustavo, Duran, Tomás Augusto Suriane Fialho, Tamires Cristina Gomes da Silva, Luiz Otavio Maia Gonçalves, Lucas Eduardo Pazetto, Luciana Renata Cubas Volpe, Luciana Souza Duca, Maurício AndréGheller Friedrich, Alexandre, Guerreiro, Henrique, Mohr, Maurer Pereira Martins, Daiane da Cruz Pacheco, Luciana, Ferreira, Ana Paula Macagnan, Graziela, Pinto, Aline de Cassia Santos, Acary Souza Bulle Oliveira, Ana Carolina Amaral de Andrade, Marcelo, Annes, Liene Duarte Silva, Valeria Cavalcante Lino, Wladimir, Pinto, Natália, Assis, Fernanda, Carrara, Carolina, Miranda, Iandra, Souza, Patrícia, Fernandes, Zaeem, Siddiqi, Cecile, Phan, Jeffrey, Narayan, Derrick, Blackmore, Ashley, Mallon, Rikki, Roderus, Elizabeth, Watt, Stanislav, Vohanka, Josef, Bednarik, Magda, Chmelikova, Marek, Cierny, Stanislava, Toncrova, Jana, Junkerova, Barbora, Kurkova, Katarina, Reguliova, Olga, Zapletalova, Jiri, Pitha, Iveta, Novakova, Michaela, Tyblova, Ivana, Jurajdova, Marcela, Wolfova, Henning, Andersen, Thomas, Harbo, Lotte, Vinge, Susanne, Krogh, Anita, Mogensen, John, Vissing, Joan, Højgaard, Nanna, Witting, Anne Mette Ostergaard Autzen, Jane, Pedersen, Juha-Pekka, Erälinna, Mikko, Laaksonen, Olli, Oksaranta, Tuula, Harrison, Jaana, Eriksson, Csilla, Rozsa, Melinda, Horvath, Gabor, Lovas, Judit, Matolcsi, Gedeonne, Jakab, Gyorgyi, Szabo, Brigitta, Szabadosne, Laszlo, Vecsei, Livia, Dezsi, Edina, Varga, Monika, Konyane, Antonini, Giovanni, Antonella Di Pasquale, Garibaldi, Matteo, Morino, Stefania, Troili, Fernanda, Fionda, Laura, Amelia, Evoli, Paolo Emilio Alboini, Valentina, D'Amato, Raffaele, Iorio, Inghilleri, Maurizio, Frasca, Vittorio, Elena, Giacomelli, Gori, MARIA CRISTINA, Diego, Lopergolo, Onesti, Emanuela, Maria, Gabriele, Francesco, Saccà, Alessandro, Filla, Teresa, Costabile, Enrico, Marano, Angiola, Fasanaro, Angela, Marsili, Giorgia, Puorro, Carlo, Antozzi, Silvia, Bonanno, Giorgia, Camera, Alberta, Locatelli, Lorenzo, Maggi, Maria, Pasanisi, Angela, Campanella, Akiyuki, Uzawa, Tetsuya, Kanai, Naoki, Kawaguchi, Masahiro, Mori, Yoko, Kaneko, Akiko, Kanzaki, Eri, Kobayashi, Hiroyuki, Murai, Katsuhisa, Masaki, Dai, Matsuse, Takuya, Matsushita, Taira, Uehara, Misa, Shimpo, Maki, Jingu, Keiko, Kikutake, Yumiko, Nakamura, Yoshiko, Sano, Kimiaki, Utsugisawa, Yuriko, Nagane, Ikuko, Kamegamori, Tomoko, Tsuda, Yuko, Fujii, Kazumi, Futono, Yukiko, Ozawa, Aya, Mizugami, Yuka, Saito, Makoto, Samukawa, Hidekazu, Suzuki, Miyuki, Morikawa, Sachiko, Kamakura, Eriko, Miyawaki, Meinoshin, Okumura, Soichiro, Funaka, Tomohiro, Kawamura, Masayuki, Nakamori, Masanori, Takahashi, Namie, Taichi, Tomoya, Hasuike, Eriko, Higuchi, Hisako, Kobayashi, Kaori, Osakada, Hirokazu, Shiraishi, Teiichiro, Miyazaki, Masakatsu, Motomura, Akihiro, Mukaino, Shunsuke, Yoshimura, Shizuka, Asada, Seiko, Yoshida, Shoko, Amamoto, Tomomi, Kobashikawa, Megumi, Koga, Maeda, Yasuko, Kazumi, Takada, Mihoko, Takada, Masako, Tsurumaru, Yumi, Yamashita, Yasushi, Suzuki, Tetsuya, Akiyama, Koichi, Narikawa, Ohito, Tano, Kenichi, Tsukita, Rikako, Kurihara, Fumie, Meguro, Yusuke, Fukuda, Miwako, Sato, Tomihiro, Imai, Emiko, Tsuda, Shun, Shimohama, Takashi, Hayashi, Shin, Hisahara, Jun, Kawamata, Takashi, Murahara, Masaki, Saitoh, Shuichiro, Suzuki, Daisuke, Yamamoto, Yoko, Ishiyama, Naoko, Ishiyama, Mayuko, Noshiro, Rumi, Takeyama, Kaori, Uwasa, Ikuko, Yasuda, Anneke van der Kooi, Marianne de Visser, Tamar, Gibson, Byung-Jo, Kim, Chang Nyoung Lee, Yong Seo Koo, Hung Youl Seok, Hoo Nam Kang, Hyejin, Ra, Byoung Joon Kim, Eun Bin Cho, Misong, Choi, Hyelim, Lee, Ju-Hong, Min, Jinmyoung, Seok, Jieun, Lee, Da Yoon Koh, Juyoung, Kwon, Sangae, Park, Eun Haw Choi, Yoon-Ho, Hong, So-Hyun, Ahn, Dae Lim Koo, Jae-Sung, Lim, Chae Won Shin, Ji Ye Hwang, Miri, Kim, Seung Min Kim, Ha-Neul, Jeong, Jinwoo, Jung, Yool-Hee, Kim, Hyung Seok Lee, Ha Young Shin, Eun Bi Hwang, Miju, Shin, Carlos, Casasnovas, Maria Antonia Alberti Aguilo, Christian, Homedes-Pedret, Natalia Julia Palacios, Laura Diez Porras, Valentina Velez Santamaria, Ana, Lazaro, Josep Gamez Carbonell, Pilar, Sune, Maria Salvado Figueras, Gisela, Gili, Gonzalo, Mazuela, Isabel, Illa, Elena Cortes Vicente, Jordi, Diaz-Manera, Luis Antonio Querol Gutiérrez, Ricardo Rojas Garcia, Nuria, Vidal, Elisabet, Arribas-Ibar, Exuperio Diez Tejedor, Pilar Gomez Salcedo, Mireya, Fernandez-Fournier, Pedro Lopez Ruiz, Francisco Javier Rodriguez de Rivera, Maria, Sastre, Fredrik, Piehl, Albert, Hietala, Lena, Bjarbo, Ihsan, Sengun, Arzu, Meherremova, Pinar, Ozcelik, Bengu, Balkan, Celal, Tuga, Muzeyyen, Ugur, Sevim, Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Nazire Pinar Acar, Ezgi, Yilmaz, Yagmur, Caliskan, Gulsah, Orsel, Husnu, Efendi, Seda, Aydinlik, Hakan, Cavus, Ayse, Kutlu, Gulsah, Becerikli, Cansu, Semiz, Ozlem, Tun, Murat, Terzi, Baki, Dogan, Musa Kazim Onar, Sedat, Sen, Tugce Kirbas Cavdar, Adife, Veske, Fiona, Norwood, Aikaterini, Dimitriou, Jakit, Gollogly, Mohamed, Mahdi-Rogers, Arshira, Seddigh, Giannis, Sokratous, Gal, Maier, Faisal, Sohail, Saiju, Jacob, Girija, Sadalage, Pravin, Torane, Claire, Brown, Amna, Shah, Sivakumar, Sathasivam, Heike, Arndt, Debbie, Davies, Dave, Watling, Anthony, Amato, Thomas, Cochrane, Mohammed, Salajegheh, Kristen, Roe, Katherine, Amato, Shirli, Toska, Nicholas, Silvestri, Kara, Patrick, Karen, Zakalik, Jonathan, Katz, Robert, Miller, Marguerite, Engel, Dallas, Forshew, Elena, Bravver, Benjamin, Brooks, Mohammed, Sanjak, Sarah, Plevka, Maryanne, Burdette, Scott, Cunningham, Megan, Kramer, Joanne, Nemeth, Clara, Schommer, Tierney, Scott, Vern, Juel, Jeffrey, Guptill, Lisa, Hobson-Webb, Janice, Massey, Kate, Beck, Donna, Carnes, John, Loor, Amanda, Anderson, Robert, Pascuzzi, Cynthia, Bodkin, John, Kincaid, Riley, Snook, Sandra, Guingrich, Angela, Micheels, Vinay, Chaudhry, Andrea, Corse, Betsy, Mosmiller, Andrea, Kelley, Doreen, Ho, Jayashri, Srinivasan, Michal, Vytopil, Jordan, Jara, Nicholas, Ventura, Cynthia, Carter, Craig, Donahue, Carol, Herbert, Stephanie, Scala, Elaine, Weiner, Sharmeen, Alam, Jonathan, Mckinnon, Laura, Haar, Naya, Mckinnon, Karan, Alcon, Kaitlyn, Mckenna, Nadia, Sattar, Kevin, Daniels, Dennis, Jeffery, Miriam, Freimer, Joseph Chad Hoyle, John, Kissel, Julie, Agriesti, Sharon, Chelnick, Louisa, Mezache, Colleen, Pineda, Filiz, Muharrem, Chafic, Karam, Julie, Khoury, Tessa, Marburger, Harpreet, Kaur, Diana, Dimitrova, James, Gilchrist, Brajesh, Agrawal, Mona, Elsayed, Stephanie, Kohlrus, Angela, Ardoin, Taylor, Darnell, Laura, Golden, Barbara, Lokaitis, Jenna, Seelbach, Neelam, Goyal, Sarada, Sakamuri, Yuen, T So, Shirley, Paulose, Sabrina, Pol, Lesly, Welsh, Ratna, Bhavaraju-Sanka, Alejandro Tobon Gonzalez, Lorraine, Dishman, Floyd, Jones, Anna, Gonzalez, Patricia, Padilla, Amy, Saklad, Marcela, Silva, Sharon, Nations, Jaya, Trivedi, Steve, Hopkins, Mohamed, Kazamel, Mohammad, Alsharabati, Liang, Lu, Kenkichi, Nozaki, Sandi, Mumfrey-Thomas, Amy, Woodall, Tahseen, Mozaffar, Tiyonnoh, Cash, Namita, Goyal, Gulmohor, Roy, Veena, Mathew, Fatima, Maqsood, Brian, Minton, H James Jones, Jeffrey, Rosenfeld, Rebekah, Garcia, Laura, Echevarria, Sonia, Garcia, Michael, Pulley, Shachie, Aranke, Alan Ross Berger, Jaimin, Shah, Yasmeen, Shabbir, Lisa, Smith, Mary, Varghese, Laurie, Gutmann, Ludwig, Gutmann, Nivedita, Jerath, Christopher, Nance, Andrea, Swenson, Heena, Olalde, Nicole, Kressin, Jeri, Sieren, Richard, Barohn, Mazen, Dimachkie, Melanie, Glenn, April, Mcvey, Mamatha, Pasnoor, Jeffery, Statland, Yunxia, Wang, Tina, Liu, Kelley, Emmons, Nicole, Jenci, Jerry, Locheke, Alex, Fondaw, Kathryn, Johns, Gabrielle, Rico, Maureen, Walsh, Laura, Herbelin, Charlene, Hafer-Macko, Justin, Kwan, Lindsay, Zilliox, Karen, Callison, Valerie, Young, Beth, Disanzo, Kerry, Naunton, Michael, Benatar, Martin, Bilsker, Khema, Sharma, Anne, Cooley, Eliana, Reyes, Sara-Claude, Michon, Danielle, Sheldon, Julie, Steele, Rebecca, Traub, Manisha, Chopra, Tuan, Vu, Lara, Katzin, Terry, Mcclain, Brittany, Harvey, Adam, Hart, Kristin, Huynh, Said, Beydoun, Amaiak, Chilingaryan, Victor, Doan, Brian, Droker, Hui, Gong, Sanaz, Karimi, Frank, Lin, Krishna, Polaka, Akshay, Shah, Anh, Tran, Salma, Akhter, Ali, Malekniazi, Rup, Tandan, Michael, Hehir, Waqar, Waheed, Shannon, Lucy, Michael, Weiss, Jane, Distad, Susan, Strom, Sharon, Downing, Bryan, Kim, Tulio, Bertorini, Thomas, Arnold, Kendrick, Henderson, Rekha, Pillai, Liu, Ye, Lauren, Wheeler, Jasmine, Hewlett, Mollie, Vanderhook, Richard, Nowak, Daniel, Dicapua, Benison, Keung, Aditya, Kumar, Huned, Patwa, Kimberly, Robeson, Irene, Yang, Joan, Nye, and Hong, Vu

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Clinical Neurology, Antibodies, Monoclonal, Humanized, Placebo, Article, Antibodies, Post-intervention, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Refractory, law, Internal medicine, Monoclonal, Myasthenia Gravis, Medicine and Health Sciences, Humans, Medicine, Humanized, Science & Technology, business.industry, Middle Aged, Eculizumab, Complement Inactivating Agents, Female, Treatment Outcome, EFFICACY, medicine.disease, Myasthenia gravis, Clinical trial, 030104 developmental biology, SAFETY, Neurosciences & Neurology, Neurology (clinical), business, Life Sciences & Biomedicine, COMPLEMENT INHIBITOR ECULIZUMAB, 030217 neurology & neurosurgery, medicine.drug
Abstract

ObjectiveTo evaluate whether eculizumab helps patients with anti–acetylcholine receptor–positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension.MethodsPatients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.ResultsA total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1–4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.ConclusionEculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.ClinicalTrials.gov IdentifierREGAIN, NCT01997229; REGAIN open-label extension, NCT02301624.Classification of EvidenceThis study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.

Published
2020
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22. Reliability and Validity of Turkish Myasthenia Gravis-Activities of Daily Living Scale

Author

Can Ebru Bekircan-Kurt, Sevim Erdem Özdamar, Yeliz Salci, Ayla Fil-Balkan, Ecem Karanfil, and Kadriye Armutlu

Subjects
Activities of daily living, Turkish, Outcome measures, Reproducibility of Results, Construct validity, Clinical settings, medicine.disease, humanities, language.human_language, Myasthenia gravis, Occupational Therapy, Surveys and Questionnaires, Scale (social sciences), Activities of Daily Living, Myasthenia Gravis, Quality of Life, language, medicine, Humans, Psychology, Reliability (statistics), Clinical psychology
Abstract

Linguistic, reliable, and valid secondary efficacy measures are important in clinical settings and studies. The aim of the study is to report test–retest reliability and construct validity of Turkish version of Myasthenia Gravis-Activities of Daily Living Scale (MG-ADL-T) in Myasthenia Gravis (MG) patients. Fifty-two ocular and generalized individuals with MG, applying to rehabilitation center, were included in the study. MG-ADL-T, MG quality-of-life questionnaire (MG-QoL), MG composite (MGC), quantitative MG score (QMGS), and pulmonary function test were administered. Reliability was assessed with intraclass correlation coefficient (ICC) and Cronbach’s alpha. Spearman correlation test and receiver operating characteristic (ROC) analysis were performed for construct validity. MG-ADL-T had fair internal consistency (Cronbach’s α = .67), excellent test–retest reliability (ICC = 0.96) and moderate construct validity (MG-QoL, r = 0.59; QMGS, r = .58; MGC, r = .68). MG-ADL, a unique scale that evaluates activities of daily living (ADL), has good test–retest reliability and construct validity in Turkish MG patients.

Published
2020
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23. A Novel Amplification-Refractory Mutation System-PCR Strategy to Screen MT-TL1 Pathogenic Variants in Patient Repositories

Author

Goknur Haliloglu, Can Ebru Bekircan-Kurt, Y. Çetin Kocaefe, Haluk Topaloglu, Hasan Basri Kiliç, Sevim Erdem Özdamar, and Bengisu Kevser Bulduk

Subjects
Genetics, Sanger sequencing, Mitochondrial DNA, Mutation, General Medicine, Ribosomal RNA, Biology, medicine.disease_cause, Heteroplasmy, High Resolution Melt, MT-TL1, symbols.namesake, symbols, medicine, Gene, Genetics (clinical)
Abstract

Aim: Pathogenic variants within mitochondrial tRNA and rRNA genes negatively affect protein synthesis function and cause oxidative phosphorylation defects. The majority of mitochondrial cytopathies are caused by pathogenic point variants within the mitochondrial tRNA gene for leucine (MT-TL1). This study was designed to evaluate a novel amplification-refractory mutation system (ARMS)-PCR based assay to screen patient samples with a clinical diagnosis of mitochondrial cytopathies. Methods: Tissue DNA samples from 219 affected individuals were screened for the pathogenic variants m.3271T>C, m.3291Ty >C, m.3303C>T, m.3256C>T, and m.3260A>G along with the most frequent m.3243A>G mutation in the MT-TL1 gene. The assay included a "High Resolution Melt curve analysis" to enhance detection limits. The precision of the assay was verified using synthetic controls with variant heteroplasmy ratios. Results: The screening identified the second reported m.3303C>T case as well as two patients with m.3243A>G variants and a rare variant exhibiting m.3290T>C. Conclusion: ARMS-PCR is superior to Sanger sequencing for the detection of variations exhibiting low heteroplasmy. These results provide "proof of concepts" for the implementation of this application for future screening of rare mtDNA variations in sample repositories.

Published
2020
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24. Comprehensive evaluation of velopharyngeal function in myasthenia gravis patients

Author

Aydan Baştuğ Dumbak, Maviş Emel Kulak Kayıkcı, Mehmet İlhan Şahin, Oğuz Kuşçu, Can Ebru Bekircan-Kurt, and Sevim Erdem Özdamar

Subjects
Adult, Velopharyngeal Insufficiency, stomatognathic system, Myasthenia Gravis, Humans, Neurology (clinical), General Medicine, nervous system diseases
Abstract

© 2022, The Author(s) under exclusive licence to Belgian Neurological Society.Purpose: Hypernasality, which is a symptom of dysarthria, may be seen in patients with Myasthenia Gravis with bulbar symptoms. However, there is not enough evidence to show that these patients may have velopharyngeal dysfunction. This study investigates the features of velopharyngeal function in myasthenia gravis patients using objective and subjective measurement tools. Methods: Ten adult myasthenia gravis patients with bulbar symptoms and ten adult myasthenia gravis patients without bulbar symptoms were recruited for this study. Ten healthy subjects were also included as the control group. The nasalance scores of the participants were determined using a nasometer. The degree and pattern of velopharyngeal closure were scored using flexible nasoendoscopy during speech, blowing, dry swallowing, and food swallowing. Perceptual hypernasality was assessed. Results: Velopharyngeal dysfunction was detected in 50% of the myasthenia gravis patients with bulbar symptoms. Velopharyngeal dysfunction was not seen in myasthenia gravis patients without bulbar symptoms. The degree of velopharyngeal closure in patients with bulbar symptoms differed depending on the tasks being performed. No significant difference in velopharyngeal closure patterns was observed between the groups (p < 0.05). Conclusion: Myasthenia gravis patients with bulbar involvement may have velopharyngeal dysfunction. It is important to conduct a comprehensive evaluation to assess all aspects of the velopharyngeal function.

Published
2022

26. Efficacy and safety of avalglucosidase alfa in participants with late-onset Pompe disease after 145 weeks of treatment during the COMET trial

Author

Priya S. Kishnani, Jordi Díaz-Manera, Hani Kushlaf, Shafeeq Ladha, Tahseen Mozaffar, Volker Straub, Antonio Toscano, Ans T. van der Ploeg, Paula R. Clemens, John W. Day, Sergey Illarioshkin, Mark E. Roberts, Shahram Attarian, Gerson Carvalho, Sevim Erdem-Özdamar, Ozlem Goker-Alpan, Anna Kostera-Pruszczyk, Kristina An Haack, Olivier Huynh-Ba, Swathi Tammireddy, Nathan Thibault, Tianyue Zhou, Mazen M. Dimachkie, and Benedikt Schoser

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Genetics, Molecular Biology, Biochemistry
Published
2023
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27. The effects of spinal stabilization exercises in patients with myasthenia gravis: a randomized crossover study

Author

Ali Naim Ceren, Yeliz Salcı, Ayla Fil Balkan, Ebru Çalık Kütükçü, Kadriye Armutlu, and Sevim Erdem Özdamar

Subjects
Adult, Young Adult, Cross-Over Studies, Adolescent, Rehabilitation, Myasthenia Gravis, Quality of Life, Humans, Middle Aged, Fatigue, Aged, Exercise Therapy
Abstract

The effects of spinal stabilization exercises (SSE) on fatigue, muscle strength, respiratory functions, functional capacity, and quality of life (QoL) in myasthenia gravis (MG) patients were investigated.This study which was designed a single-blinded, randomized crossover trial were included mild to moderate 10 MG patients, aged between 18 and 65. SSE and home program were applied to the patients for six weeks, four weeks between each exercise program. Fatigue assessed with Fatigue Severity Scale (FSS) and Visual Analog Fatigue Scale (VAFS). Muscle strengths were assessed with dynamometric measures. Respiratory Function Test, 6 Minute Walk Test (6MWT), Quantitative Myasthenia Gravis Score (QMGS), Myasthenia Gravis Quality of Life Scale-15 (MGQOL-15) were used.All parameters were improved in SSE group, but not neck muscles strength, QMGS, and respiratory functions in home program group. FSS, VAFS, muscle strength, 6MWT, MGQOL-15 values were found significantly different in SSE group (SSE are safe and effective on fatigue, muscle strength, respiratory functions, functional capacity, and QoL for MG patients, so it may be suggested to include SSE in rehabilitation programs of MG patients.Implications For RehabilitationSpinal stabilization exercises are safe and effective for Myasthenia Gravis patients.Home exercise program which included breathing exercises and callisthenic exercises tailored to the patients' needs is safe and effective for Myasthenia Gravis patients.Rehabilitation programs of Myasthenia Gravis patients should include spinal stabilization exercises.

Published
2022

28. Toscana virus associated with Guillain–Barré syndrome: a case–control study

Author

Koray Ergünay, Can Ebru Bekircan-Kurt, Sevim Erdem-Ozdamar, Serhat Okar, Aykut Ozkul, and Sabri Hacıoğlu

Subjects
biology, Guillain-Barre syndrome, Toscana virus, business.industry, viruses, Polyradiculoneuropathy, General Medicine, biology.organism_classification, medicine.disease, medicine.disease_cause, Virology, Virus, Dengue fever, Serology, 03 medical and health sciences, 0302 clinical medicine, medicine, biology.protein, 030212 general & internal medicine, Neurology (clinical), Chikungunya, Antibody, business, 030217 neurology & neurosurgery
Abstract

Guillain–Barre syndrome (GBS) is an acute-onset, immune-mediated polyradiculoneuropathy, often precipitated by an antecedent infection. An association of GBS with vector-borne viral infections has been suggested, with evidence for the involvement of Zika, Dengue, Chikungunya and West Nile virus (WNV). This prospective case–control study was conducted to identify vector-borne viral infections in GBS. Thirteen individuals newly diagnosed as GBS were enrolled. Disease severity, prognostic factors and nerve conduction patterns were assessed. Eleven individuals with non-infectious conditions requiring cerebrospinal fluid (CSF) analysis were included as controls. Plasma, CSF and urine specimens were evaluated via nucleic acid amplification assays aimed to detect a broad spectrum of viruses. WNV and Toscana virus (TOSV) IgM/IgG antibodies were screened using commercial immunofluorescence assays and confirmed via virus neutralization tests (VNT). Partial TOSV nucleocapsid and genotype 1 polymerase sequences were detected in CSF of a patient with normal pressure hydrocephalus. Two control subjects had VNT-confirmed TOSV IgM in plasma. VNT-confirmed WNV and TOSV IgG were detected in 15.4% and 61.5% of GBS patients, respectively. Variations in WNV IgG and TOSV IgM detection rates were not statistically significant among study cohorts. However, TOSV IgG was significantly more frequent in GBS patients. No difference was observed for disease form or prognostic scores for virus markers. Follow-up serological profiles were identical to the initial findings. We have identified TOSV as a potential precipitating agent in GBS, with some rare clinical presentations of symptomatic TOSV infections.

Published
2020
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29. The avalglucosidase alfa phase 3 COMET trial in late-onset Pompe disease patients: Efficacy and safety results after 97 weeks

Author

Priya Kishnani, Jordi Díaz-Manera, Hani Kushlaf, Shafeeq Ladha, Tahseen Mozaffar, Volker Straub, Antonio Toscano, Ans T. van der Ploeg, Kenneth I. Berger, Paula R. Clemens, Yin-Hsiu Chien, John W. Day, Sergey Illarioshkin, Mark Roberts, Shahram Attarian, Gerson Carvalho, Young-Chul Choi, Sevim Erdem-Özdamar, Ozlem Goker-Alpan, Anna Kostera-Pruszczyk, Kristina An Haack, Nathan Thibault, Tianyue Zhou, Mazen M. Dimachkie, and Benedikt Schoser

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Genetics, Molecular Biology, Biochemistry
Published
2022
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30. FORESTS OTTOMAN EMPİRE - USE OF FOREST AND LEGAL REGULATIONS

Author

Sevim ERDEM and Ahmet BAŞKAN

Subjects
Social sciences (General), H1-99, Social Sciences, ottoman empire, forest law and regulations
Abstract

The Ottoman Empire, the organization during the fall period up has not much importance to the production or the forest products forestry activities in the period and the production area only in rural areas of taxation means is seen as war and the palace meeting the needs of the vehicle. Reforms Dönemi'yl with natural forests and property values begin to understand the self-regulation by the Ottoman Empire for the forest, it has issued codes of law. Forestry General Directorate of Forestry and Forest School Provincial Organization of rich forests for timber sales through auctions on the other hand have started to show sensitivity to the protection of the established forest were carried out. The first efforts to protect forests and to regulate forestry activities in the Ottoman Empire has been Abdulmecit period. Forestry Directorate was established in 1839 Abdulmecit period. A forest protection staff in 1851 was prepared. Launched westernization attempts at each site with a wriggling mAlArA Tanzimat led teams in forestry. In the Ottoman Empire, the largest arrangements related to forestry activities during the period of Sultan Abdulaziz Forest Regulations 1870 has been removed. This regulation remained in practice until 1937. Especially the structure of the Constitutional period of Forestry Directorates after the Tanzimat period, the introduction of foreign forestry experts, their exploration and mapping work, the forest and the establishment of the Agricultural School of the administrative and legal arrangements for the Ottoman Forestry was given in the form of implementation in the Ottoman geography of these regulations. Organization of forest remaining in the background, our goal is to do research in this particularly Ottoman Economic History and bureaucratic structure, will reveal forestry activities.

Published
2019

32. Cane sign: sciatic neuropathy appearance in magnetic resonance imaging

Author

Sevim Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Ersin Tan, Berin Inan, and Onur Akca

Subjects
Sciatic Neuropathy, Nuclear magnetic resonance, nervous system, medicine.diagnostic_test, business.industry, IDIOPATHIC SCIATIC NEUROPATHY, Medicine, Magnetic resonance imaging, General Medicine, equipment and supplies, business, human activities, Sign (mathematics)
Abstract

We present a patient with idiopathic sciatic neuropathy with demonstrative magnetic resonance imaging findings.

Published
2021
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33. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial

Author

Stella Mazurová, John W. Day, Mazen M. Dimachkie, Sónia Tizon, Anna Kostera-Pruszczyk, Tahseen Mozaffar, Joel Charrow, Chafic Karam, Ricardo Maré, Jean-Baptiste Noury, Dewi Guellec, Jorge Alonso-Pérez, Acary Souza Bulle Oliveira, Loren D M Pena, Tianyue Zhou, Sergey Illarioshkin, Nathan Thibault, Marcelo Rugiero, Can Ebru Bekircan-Kurt, Lauren Chase, Monica Sciacco, Mamatha Pasnoor, Jenny Billy, Mark Tarnopolsky, Fabien Zagnoli, Marie Wencel, Sevim Erdem-Ozdamar, Erin Hatcher, Madoka Mori, Céline Tard, Nicolas Mavroudakis, Emmanuelle Salort-Campana, Antonio Toscano, Shafeeq Ladha, Angela Genge, Ans T. van der Ploeg, Michela Guglieri, Judith Johnson, Fanny Duval, Loïc Danjoux, Christopher Hug, Robert D. Henderson, Robert Neel, Luca Solera, Aleksandra Nadaj-Pakleza, Silvia Boschi, Nizar Chahin, Maurizio Gualtiero Moggio, Peter Young, Priya S. Kishnani, Yin-Hsiu Chien, Alexandra Kautzky-Willer, Claire Questienne, Francoise Bouhour, Gabriela A Niizawa, Ekaterina Fedotova, Tiziana Enrica Mongini, Harmke A. van Kooten, Vera Malinova, Sina Helms, Shahram Attarian, Patrick Deegan, Guilhem Sole, Hamilton Cirne, Ludwig Gutmann, Kenneth I. Berger, Laura Carrera Garcia, N A M E van der Beek, Stephanie Dearmey, Suzara Souto Lopes, Anna Potulska-Chromik, Joao Lindolfo Borges, Yesim Parman, Michaela Riedl, Sergey A. Klyushnikov, Olivier Huynh-Ba, Gauthier Remiche, Paula R. Clemens, Andrea Swenson, Stephan Wenninger, Miriam Hufgard-Leitner, Eugen Mengel, Kristina An Haack, Eve Gandolfo, David Reyes-Leiva, Jean-Baptiste Davion, Chester Whitley, Young Chul Choi, Patricia Altemus, Maria Judit Molnar, Perry B. Shieh, Matthias Vorgerd, Julia B Hennermann, Cheryl Smith, Volker Straub, Lauren Noll, Pascal Laforet, Andres Nascimento Osorio, Clarisa Maxit, Anne-Catherine Aubé-Nathier, Ozlem Goker-Alpan, Olimpia Musumeci, Louisa Müller-Miny, Tarekegn Hiwot, Jacqui Langton, Christopher Nance, Daniel Natera-de Benito, Jeffrey Statland, Nicola Longo, Vivien Pautot, Zoltan Grosz, Thomas Stulnig, Matthias Boentert, Anne-Katrin Guettsches, Chong Yew Tan, Erik Ortega, Derralynn Hughes, Hacer Durmus Tekce, Mark Roberts, Lenka Linková, Amel Karaa, Hani Kushlaf, Anthony Behin, Margarida Ramos Lopes, Jordi Diaz-Manera, Alessia Pugliese, Paulo Victor Sgobbi Souza, Carrie Bailey, Jennifer B Avelar, Hirofumi Komaki, Frederic Taithe, Benedikt Schoser, Sabine Specht, Kathryn E Brown, Gerson Carvalho, and Pediatrics

Subjects
medicine.medical_specialty, Population, Walking, FEV1/FVC ratio, stomatognathic system, SDG 3 - Good Health and Well-being, Double-Blind Method, Internal medicine, Statistical significance, Child, Preschool, Enzyme Replacement Therapy, Humans, Treatment Outcome, Glycogen Storage Disease Type II, alpha-Glucosidases, medicine, Respiratory function, Adverse effect, education, Child, Preschool, Alglucosidase alfa, education.field_of_study, business.industry, Standard treatment, virus diseases, Enzyme replacement therapy, Neurology (clinical), business, medicine.drug
Abstract

Summary Background Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. Methods We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov , NCT02782741 . We report results of the 49-week primary analysis period. Findings Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI −0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). Interpretation We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease. Funding Sanofi Genzyme.

Published
2021

34. Beliren yetişkinlik döneminde kimlik biçimlenme süreçlerinin iyi oluşa etkisinin öyküsel kimlik yaklaşımı ile incelenmesi : karma bir araştırma = Examination of the effects of identity formation processes on well-being in emerging adulthood using the narr

Author

Sevim, Erdem, Otrar, Mustafa, and Eğitim Bilimleri Anabilim Dalı Rehberlik ve Psikolojik Danışmanlık Bilim Dalı

Subjects
Eğitim, Psychological counseling and guidance, Education, Psikolojik danışmanlık ve rehberlik
Abstract

Bu çalışmada, kimlik biçimlenme süreçlerinin psikolojik iyi oluşa olan etkisi öyküsel kimlik modeli yaklaşımı çerçevesinde ele alınmıştır. Araştırma problemin daha bütüncül ve detaylı bir şekilde incelemek için açımlayıcı sıralı desene göre yapılandırılan

Published
2021

36. Comprehensive clinical, biochemical, radiological and genetic analysis of 28 Turkish cases with suspected metachromatic leukodystrophy and their relatives

Author

Can Ebru Bekircan-Kurt, Faruk Pekgül, Sevim Erdem-Ozdamar, Nurten A. Akarsu, Ersin Tan, Hatice Asuman Özkara, Bahadır Konuşkan, Meral Topçu, Arda Cetinkaya, Nesibe Gevher Eroglu‐Ertugrul, Banu Anlar, Kader Karli Oguz, and Ergun Karaagaoglu

Subjects
medicine.medical_specialty, Arylsulfatase A, Turkish population, SUMF1, Gastroenterology, complex mixtures, Metachromatic leukodystrophy, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Multiple sulfatase deficiency, Internal medicine, Genotype, Genetics, Medicine, Missense mutation, lcsh:QH301-705.5, Molecular Biology, Antibody, lcsh:R5-920, 0303 health sciences, business.industry, 030305 genetics & heredity, medicine.disease, lcsh:Biology (General), Pseudodeficiency alleles, ARSA, Urinary sulfatide, Age of onset, lcsh:Medicine (General), business, 030217 neurology & neurosurgery, Research Paper, MRI
Abstract

Metachromatic leukodystrophy (MLD) is a glycosphingolipid storage disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ASA) or its activator protein saposin B. MLD can affect all age groups in severity varying from a severe fatal form to milder adult onset forms. Diagnosis is usually made by measuring leukocyte ASA activity. However, this test can give false negative or false positive laboratory results due to pseudodeficiency of ASA and saposin B deficiency, respectively. Therefore, we aimed to evaluate patients with suspected MLD in a Turkish population by comprehensive clinical, biochemical, radiological, and genetic analyses for molecular and phenotypic characterization. We analyzed 28 suspected MLD patients and 41 relatives from 24 families. ASA activity was found to be decreased in 21 of 28 patients. Sixteen patients were diagnosed as MLD (11 late infantile, 2 juvenile and 3 adult types), 2 MSD, 2 pseudodeficiency (PD) and the remaining 8 patients were diagnosed as having other leukodystrophies. Enzyme analysis showed that the age of onset of MLD did not correlate with residual ASA activity. Sequence analysis showed 11 mutations in ARSA, of which 4 were novel (p.Trp195GlyfsTer5, p.Gly298Asp, p.Arg301Leu, and p.Gly311Asp), and 2 mutations in SUMF1 causing multiple sulfatase deficiency, and confirmed the diagnosis of MLD in 2 presymptomatic relatives. All individuals with confirmed mutations had low ASA activity and urinary sulfatide excretion. Intra- and inter-familial variability was high for the same ARSA missense genotypes, indicating the contribution of other factors to disease expression. Imaging findings were evaluated through a modified brain MRI scoring system which indicated patients with protein-truncating mutations had more severe MRI findings and late-infantile disease onset. MRI findings were not specific for the diagnosis. Anti-sulfatide IgM was similar to control subjects, and IgG, elevated in multiple sulfatase deficiency. In conclusion, the knowledge on the biochemical, clinical and genetic basis of MLD was expanded, a modified diagnostic laboratory algorithm for MLD based on integrated evaluation of ASA activity, urinary sulfatide excretion and genetic tests was devised.

Published
2020

37. Response to eculizumab in patients with myasthenia gravis recently treated with chronic IVIg: a subgroup analysis of REGAIN and its open-label extension study

Author

Saiju Jacob, Hiroyuki Murai, Kimiaki Utsugisawa, Richard J. Nowak, Heinz Wiendl, Kenji P. Fujita, Fanny O’Brien, James F. Howard, Claudio Gabriel Mazia, Miguel Wilken, Fabio Barroso, Juliet Saba, Jan De Bleecker, Guy Van den Abeele, Kathy de Koning, Katrien De Mey, Alzira Alves de Siqueira Carvalho, Igor Dias Brockhausen, David Feder, Daniel Ambrosio, Pamela César, Ana Paula Melo, Renata Martins Ribeiro, Rosana Rocha, Bruno Bezerra Rosa, Thabata Veiga, Luiz Augusto da Silva, Murilo Santos Engel, Jordana Gonçalves Geraldo, Yuriko Nagane, Ikuko Kamegamori, Tomoko Tsuda, Yuko Fujii, Kazumi Futono, Yukiko Ozawa, Aya Mizugami, Yuka Saito, Anneke van der Kooi, Marianne de Visser, Tamar Gibson, Seung Min Kim, JinWoo Jeong, Ha-Neul Jung, Yool-hee Kim, Hyung Seok Lee, Ha Young Shin, Eun Bi Hwang, Miju Shin, Josep Gamez Carbonell, Pilar Sune, Maria Salvado Figueras, Gisela Gili, Gonzalo Mazuela, Fredrik Piehl, Albert Hietala, Lena Bjarbo, Sevim Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Nazire Pinar Acar, Ezgi Yilmaz, Yagmur Caliskan, Gulsah Orsel, Anthony Amato, Thomas Cochrane, Mohammed Salajegheh, Kristen Roe, Katherine Amato, Shirli Toska, Jonathan McKinnon, Laura Haar, Naya McKinnon, Karan Alcon, Kaitlyn McKenna, Nadia Sattar, Kevin Daniels, Dennis Jeffery, Tahseen Mozaffar, Tiyonnoh Cash, Namita Goyal, Gulmohor Roy, Veena Mathew, Fatima Maqsood, Brian Minton, Charlene Hafer-Macko, Justin Kwan, Lindsay Zilliox, Karen Callison, Valerie Young, Beth DiSanzo, Kerry Naunton, Tuan Vu, Lara Katzin, Terry McClain, Brittany Harvey, Adam Hart, Kristin Huynh, Said Beydoun, Amaiak Chilingaryan, Victor Doan, Brian Droker, Hui Gong, Sanaz Karimi, Frank Lin, Krishna Polaka, Akshay Shah, Anh Tran, Salma Akhter, Ali Malekniazi, Rup Tandan, Michael Hehir, Waqar Waheed, Shannon Lucy, Tulio Bertorini, Thomas Arnold, Kendrick Hendersen, Rekha Pillai, Ye Liu, Lauren Wheeler, Jasmine Hewlett, and Mollie Vanderhook

Subjects
IVIg, 0301 basic medicine, medicine.medical_specialty, REGAIN, Subgroup analysis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Refractory, intravenous immunoglobulin, Internal medicine, medicine, In patient, Generalized myasthenia, RC346-429, Original Research, Pharmacology, myasthenia gravis, business.industry, Extension study, Eculizumab, medicine.disease, Myasthenia gravis, 030104 developmental biology, Neurology, eculizumab, Neurology (clinical), Neurology. Diseases of the nervous system, Open label, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: In the phase III eculizumab for refractory generalized myasthenia gravis REGAIN study [ClinicalTrials.gov identifier: NCT01997229] and its open-label extension (OLE) [ClinicalTrials.gov identifier: NCT02301624], patients with treatment-refractory antiacetylcholine receptor antibody-positive generalized myasthenia gravis had clinically meaningful improvements with eculizumab versus placebo. This subgroup analysis evaluated data from patients with a recent history of chronic intravenous immunoglobulin (IVIg) use before study entry. Methods: The subgroup comprised patients who had received IVIg at least four times in 1 year, with at least one IVIg treatment cycle during the 6 months before the first REGAIN study dose. Data from REGAIN and the OLE were analyzed. Response to eculizumab versus placebo was assessed using four validated, disease-specific measures. Incidences of exacerbations and safety endpoints were recorded. Results: The subgroup had similar patient and disease characteristics as the overall REGAIN population. Clinical assessments showed sustained eculizumab efficacy during REGAIN and the OLE over 18 months. Patients receiving placebo in REGAIN experienced rapid improvements in assessment scores when treated with eculizumab in the OLE. There was a lower rate of disease exacerbations with eculizumab than with placebo during REGAIN, and eculizumab was well tolerated. Conclusion: Eculizumab treatment, compared with placebo, results in meaningful clinical improvements and fewer disease exacerbations for patients who previously received chronic IVIg. Trial registration: REGAIN [ClinicalTrials.gov identifier: NCT01997229]; REGAIN open-label extension [ClinicalTrials.gov identifier: NCT02301624].

Published
2020

38. A Novel Amplification-Refractory Mutation System-PCR Strategy to Screen

Author

Bengisu Kevser, Bulduk, Hasan Basri, Kiliç, Can Ebru, Bekircan-Kurt, Göknur, Haliloğlu, Sevim, Erdem Özdamar, Haluk, Topaloğlu, and Y Çetin, Kocaefe

Subjects
Male, RNA, Transfer, Leu, Mutation, Humans, Mitochondrial Myopathies, Female, Kearns-Sayre Syndrome, DNA, Mitochondrial, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Proof of Concept Study, Sensitivity and Specificity, Mitochondria
Published
2020

39. Home-infusion experience in patients with Pompe disease receiving avalglucosidase alfa during three clinical trials (COMET, NEO-EXT, and Mini-COMET)

Author

Jordi Díaz-Manera, Derralynn Hughes, Anthony Béhin, Françoise Bouhour, James Davison, Sevim Erdem-Özdamar, Si Houn Hahn, Kristina An Haack, Olivier Huynh-Ba, Magali Periquet, Swathi Tammireddy, Nathan Thibault, Tianyue Zhou, Céline Tard, and Ans T. van der Ploeg

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Genetics, Molecular Biology, Biochemistry
Published
2022
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40. Establishment of primary myoblast cell cultures from cryopreserved skeletal muscle biopsies to serve as a tool in related research & development studies

Author

Burcu Balci-Hayta, Can Ebru Bekircan-Kurt, Didem Dayangac-Erden, Ersin Tan, Sevim Erdem-Ozdamar, and Evrim Aksu

Subjects
Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Time Factors, Cell Survival, Biopsy, Primary Cell Culture, Biology, Muscular Dystrophies, Cryopreservation, Myoblasts, Young Adult, 03 medical and health sciences, medicine, Humans, Myocyte, Muscle, Skeletal, Cell Proliferation, Muscle biopsy, medicine.diagnostic_test, MEF2 Transcription Factors, Myogenesis, Skeletal muscle, Middle Aged, 030104 developmental biology, medicine.anatomical_structure, Neurology, Karyotyping, Cryopreserved Tissue, Female, Desmin, Neurology (clinical)
Abstract

Background Primary myoblast cell cultures display the phenotypic characteristics and genetic defects of the donor tissue and represent an in vitro model system reflecting the disease pathology. They have been generated only from freshly harvested tissue biopsies. Here, we describe a novel technique to establish myoblast cell cultures from cryopreserved skeletal muscle biopsy tissues that are useful for diagnostic and research purposes. Methods and results This protocol was performed on seven gradually frozen muscle biopsy specimens from various neuromuscular disorders that were stored in dimethylsulfoxide (DMSO)-supplemented freezing media at −80 °C for up to one year. After storage for varying periods of time, primary myoblast cultures were successfully established from all cryopreserved biopsy tissues without any chromosomal abnormality. Desmin immunoreactivity confirmed that the cell cultures contained >90% pure myoblasts. The myoblasts differentiated into multinucleated myotubes successfully. Furthermore, there were no statistically significant differences in cell viability, metabolic activity, population doubling time, and myocyte enhancer factor 2 (MEF2C) expression between cell cultures established from freshly harvested and one year-stored frozen tissue specimens. Conclusions This protocol opens up new horizons for basic research and the pre-clinical studies of novel therapies by using cryopreserved skeletal muscle biopsies stored under suitable conditions in tissue banks.

Published
2018
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41. Ocular surface alterations and in vivo confocal microscopic characteristics of corneas in patients with myasthenia gravis

Author

Figen Bezci, Sevim Erdem-Ozdamar, Can Ebru Bekircan-Kurt, Kadriye Erkan Turan, Murat Irkec, and Sibel Kocabeyoglu

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Confocal, Cell Count, Ophthalmic Nerve, Corneal Diseases, Cornea, Young Adult, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, In vivo, Ophthalmology, Myasthenia Gravis, Humans, Medicine, Ocular Surface Disease Index, In patient, Aged, Microscopy, Confocal, business.industry, Epithelium, Corneal, General Medicine, Middle Aged, medicine.disease, Myasthenia gravis, Epithelium, Staining, 030104 developmental biology, medicine.anatomical_structure, 030221 ophthalmology & optometry, Female, business
Abstract

Purpose: To evaluate ocular surface alterations and characteristics of corneal basal epithelium and subbasal nerves in patients with myasthenia gravis. Materials and methods: Myasthenia gravis patients (n = 21) and healthy controls (n = 20) were enrolled. All participants underwent ocular surface testing in the following order: tear break-up time, lissamine green staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index questionnaire. The Cochet-Bonnet esthesiometer was used to measure corneal sensitivity. Basal epithelial cells and subbasal nerves were evaluated using in vivo confocal microscopy. Results: Myasthenia gravis patients had higher Ocular Surface Disease Index score (13.9 ± 15.0 vs 1.4 ± 2.2, p < 0.001) and lissamine green staining score (0.6 ± 0.4 vs 0.2 ± 0.4, p = 0.007). Break-up time score (9.3 ± 3.0 vs 9.9 ± 1.9, p = 0.481) and Schirmer I test score (16.5 ± 9.2 vs 19.3 ± 8.4, p = 0.323) did not differ significantly. Corneal sensation was 0.4 g/mm2 in all eyes. Patients with myasthenia gravis had lower basal epithelial cell density (3775.7 ± 938.1 vs 4983.1 ± 608.5, p < 0.001) and total nerve density (1956.1 ± 373.3 vs 2277.9 ± 405.0, p = 0.012) and higher subbasal nerve tortuosity (1.9 ± 0.8 vs 1.6 ± 0.7, p = 0.007) than controls. A significant increase in Ocular Surface Disease Index scores was found with decreasing basal epithelial cell density (rho = −0.518, p = 0.001). There was a significantly moderate negative correlation between the duration of myasthenia gravis and the number of corneal nerves (rho = −0.497, p = 0.022). Conclusion: Significant alterations of basal epithelial cells and subbasal nerves were demonstrated in myasthenia gravis patients although there was no difference of corneal sensitivity between myasthenia gravis patients and healthy controls. Thus, it should be borne in mind that myasthenia gravis patients deserve further evaluation with regard to ocular surface disease.

Published
2018
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42. STIGMA AND DISCRIMINATION TOWARDS PEOPLE LIVING WITH HIV/AIDS: A QUALITATIVE STUDY, ISTANBUL/TURKEY.

Author

ORNEK, Ozlem Koseoglu and SEVIM, Erdem

Subjects
HIV infections, ANTIRETROVIRAL agents, DISCRIMINATION (Sociology), SOCIAL stigma
Abstract

Copyright of International Anatolian Journal of Social Sciences / Uluslararasi Anadolu Sosyal Bilimler Dergisi is the property of Uluslararasi Anadolu Sosyal Bilimler Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022
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44. Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP): A Database Analysis (3987)

Author

Erdogan, Cagdas, primary, Bayrak, Ayse Oytun, additional, Uluc, Kayihan, additional, Karli, Necdet, additional, Koc, Filiz, additional, Ozturk, Serefnur, additional, Sengun, Ihsan Sukru, additional, Secil, Yaprak, additional, Tutuncu, Melih, additional, Akalin, Mehmet Ali, additional, Uysal, Hilmi, additional, Ozdamar, Sevim Erdem, additional, and Parman, Yesim, additional

Published
2020
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45. 199 Numaralı (H. 1322-1324 / M.1904-1907) Mahmûd Paşa Mahkemesi Şer´Îyye Sicilin

Author

Sevim Erdem and Hülya Arat

Abstract

Istanbul sehri tarih boyunca cok sayida imparatorluk ve kulture baskentlik yapmistir. Bu vasiflarindan oturu hem konumuyla hem de sahip oldugu tarihi zenginlikleriyle arastirilmaya deger ozelligini daima korumustur. Bu dogrultuda Osmanli tarihiyle ilgili dogru bilgilere ulasilmasini saglayan birinci elden kaynak olan seriyye sicilleri hic suphesiz bu amac ugrunda en kayda deger kayitlardir. 199 Numarali Mahmud Pasa Mahkemesi Ser´iyye Sicili’nin transkripsiyon ve degerlendirilmesi sonucunda cok sayidaki davanin alacak verecek ile alakali oldugu tespit edilmistir. Bunun sebebi ise 17. yuzyillarda bir ikamet alani olan Mahmud Pasa Semti’nin 20. yuzyilda artik tamamen bir ticaret semti olmasidir. Bu calismamiz, H.1322-1324/M.1904-1907 yillari arasini kapsayan 199 Numarali Mahmud Pasa Mahkemesi Ser´iyye Sicili’nin transkripsiyonu ve degerlendirmesini icermekle birlikte ulastigimiz bilgiler isiginda Musluman ve gayrimuslim unsurlar arasinda ve diger azinliklar veya sadece Osmanli vatandaslarinin arasindaki alacak veya benzer davalarin hukuki boyutu uzerinde durulmustur.

Published
2018
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46. One Disease with two Faces: Semidominant Inheritance of a Novel HTRA1 Mutation in a Consanguineous Family

Author

Figen Soylemezoglu, Arda Cetinkaya, Rahsan Gocmen, Mehmet Akif Topcuoglu, Sevim Erdem-Ozdamar, Can Koşukcu, Can Ebru Bekircan-Kurt, Aslı Tuncer, Ethem Murat Arsava, and Nurten A. Akarsu

Subjects
Adult, Male, Heterozygote, Candidate gene, Heredity, DNA Mutational Analysis, CADASIL, medicine.disease_cause, Severity of Illness Index, Consanguinity, symbols.namesake, Leukoencephalopathies, medicine, Humans, Genetic Predisposition to Disease, Age of Onset, Allele, Genetic testing, Sanger sequencing, Genetics, Mutation, medicine.diagnostic_test, business.industry, Homozygote, Rehabilitation, Alopecia, Cerebral Infarction, High-Temperature Requirement A Serine Peptidase 1, Middle Aged, medicine.disease, Disease gene identification, eye diseases, Pedigree, SNP genotyping, Phenotype, symbols, Female, Spinal Diseases, Surgery, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract

Objectives To identify the underlying genetic defect for a consanguineous family with an unusually high number of members affected by cerebral small vessel disease. Materials and methods A total of 6 individuals, of whom 3 are severely affected, from the family were clinically and radiologically evaluated. SNP genotyping was performed in multiple members to demonstrate genome-wide runs-of-homozygosity. Coding variants in the most likely candidate gene, HTRA1 were explored by Sanger sequencing. Published HTRA1-related phenotypes were extensively reviewed to explore the effect of number of affected alleles on phenotypic expression. Results Genome-wide homozygosity mapping identified a 3.2 Mbp stretch on chromosome 10q26.3 where HTRA1 gene is located. HTRA1 sequencing revealed an evolutionarily conserved novel homozygous c.824C>T (p.Pro275Leu) mutation, affecting the serine protease domain of HtrA1. Early-onset of cognitive and motor deterioration in homozygotes are in consensus with CARASIL. However, there was a clear phenotypic variability between homozygotes which includes alopecia, a suggested hallmark of CARASIL. All heterozygotes, presenting as CADASIL type 2, had spinal disk degeneration and several neuroimaging findings, including leukoencephalopathy and microhemorrhage despite a lack of severe clinical presentation. Conclusion Here, we clearly demonstrate that CARASIL and CADASIL type 2 are two clinical consequences of the same disorder with different severities thorough the evaluation of the largest collection of homozygotes and heterozygotes segregating in a family. Considering the semi-dominant inheritance of HTRA1-related phenotypes, genetic testing and clinical follow-up must be offered for all members of a family with HTRA1 mutations regardless of symptoms.

Published
2021
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47. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study

Author

Kazumi Takada, Vladislav Abramov, Seiko Yoshida, Pinar Ozcelik, Carolina Miranda, Jennifer Kane, Kaitlyn McKenna, Natasha Campbell, Sharon P. Nations, Shitiz Kumar Sriwastava, Yuko Fujii, Mayumi Murata, Linda Wagemaekers, Angela Andoin, Mollie Vanderhook, Yoshinori Okubo, Martin Bilsker, Taira Uehara, Vera Bril, Julia Wanschitz, Stanislava Toncrova, Mariela Bettini, Kazumi Futono, Shachie Aranke, Yool-hee Kim, Hiroyuki Murai, Anne Nyrhinen, Vinay Chaudhry, Raffaele Iorio, Takashi Kanda, Brittany Harvey, Francisco Javier Rodriguez de Rivera, Henning Andersen, Marianne de Visser, Miwako Sato, Yasuhiro Maeda, Fabienne Deruelle, Marina Pozo, Adam Hart, Masaki Saitoh, Wladimir Bocca Vieira de Rezende Pinto, Said R. Beydoun, Lindsay Zilliox, Akihiro Mukaino, Cinzia Caserta, Mahi Jasinarachchi, Andrea M. Corse, Nikoletta Papadopoulou, JuYoung Kwon, Fernanda Carrara, Juliet Saba, Masayuki Makamori, Vittorio Frasca, Luciana Souza Duca, Hoo Nam Kang, C. Trebst, Celile Phan, Muzeyyen Ugur, Eduardo Ng, Jonathan McKinnon, Hila Bali Kuperman, David Feder, Judit Matolcsi, Jiri Pitha, Martin Stangel, Kate Beck, Gabriel Paiva, Diego Lopergolo, Katrien De Mey, Hidenori Matsuo, Lucas Eduardo Pazetto, Eugene Lai, Amanda Anderson, Ann D'Hondt, Tetsuya Akiyama, Beverly Fyfe, Bella Gross, Elisabet Arribas-Ibar, Kathy de Koning, Gulmohor Roy, Dmitry Pokhabov, Maria Johanna Keijzers, Nicholas Ventura, Tessa Marburger, John Loor, Ji Eun Lee, Alessandro Filla, Celal Tuga, Stephanie Scala, Rudy Mercelis, Marc H. De Baets, Hisako Kobayashi, Stanislav Vohanka, Ana Paula Macagnan, Ana Carolina Amaral de Andrade, Heike Arndt, Giovanni Antonini, Yumi Yamashita, Gwendal Le Masson, Sonia Garcia, Sarah Verjans, James F. Howard, Zaeem A. Siddiqi, Yuen T. So, Megumi Koga, Exuperio Diez Tejedor, Teresa Costabile, Mihoko Takada Takada, Steve Hopkins, Jonathan S. Katz, Charlene Hafer-Macko, Erica Nogueira Coelho, Hung Youl Seok, Carol Herbert, Yuriko Nagane, Didem Altiparmak, Sachiko Kamakura, Mohammad Sanjak, Caroline Moreau, Jordi Díaz-Manera, Sivakumar Sathasivam, Michael Vytopil, Amelia Evoli, Masakatsu Motomura, Ester Reggio, Guy Van den Abeele, Hélène Zéphir, Asya Yarmoschuk, Jasmine Hewlett, Amy Wilson, Sachie Fukui, Cavit Boz, Iandra Souza, Morgane Gaboreau, Ivana Jurajdova, Sonia Decressac, Yong Seo Koo, Valentina Pegoraro, Seung Min Kim, Benison Keung, Rosana Rocha, Nanna Witting, John Vissing, Elaine Weiner, Ali Malekniazi, Larisa Babenko, Amanda C. Guidon, Gal Maier, Charlotte Smetcoren, Robert M. Pascuzzi, Domenico Marco Bonifati, Yumiko Nakamura, Tamires Cristina Gomes da Silva, Takashi Murahara, Sarah Plevka, Tomoko Tsuda, John C. Kincaid, Arnaud Lacour, Ibrez Bandukwala, Alan R. Berger, Chang Nyoung Lee, Jae-Sung Lim, Vern C. Juel, Tulio E. Bertorini, Valeria Cavalcante Lino, Namie Taichi, Ju-Hong Min, Josep Gamez, Nelly Greenbereg, William S. David, Srikanth Muppidi, Husnu Efendi, Pedro Lopez Ruiz, Baki Dogan, Cansu Semiz, Natalia Julia Palacios, Sharon Downing, Paola Cudia, Daniel Jacobs, Can Ebru Bekircan-Kurt, Takayasu Fukudome, Kristen Roe, Lena Bjarbo, Nicole Kassebaum, Makoto Samukawa, Shizuka Asada, Christina Dheel, Fatima Maqsood, Eun Bi Hwang, Kevin Daniels, Sevim Erdem-Ozdamar, Olivier Stevens, Claudio Mazia, Karan Alcon, Sibel Gazioglu, Keiko Kikutake, Luis Lay, Petra Tilkin, Corrado Angelini, Derrick Blackmore, Kimiaki Utsugisawa, Despoina Charalambous, Tuula Harrison, Kristin Huynh, Huned S. Patwa, Laura Echevarria, Henrique Mohr, Christian Homedes-Pedret, Richard J. Barohn, Byung Jo Kim, Daniel DiCapua, Terry McClain, Debora Dada Martineli Torres, Maria Salvado Figueras, Ana Paula Melo, Riley Snook, Miki Ogawa, Marcelo Annes, Yuka Saito, Isabel Illa, Evanthia Bernitsas, Nicole Smalley, Molly Lindsay, Robert G. Miller, Olga Azrilin, Silvia Bonanno, Evgeniya Kosykh, Marcela Wolfova, Olivier Outteryck, Shirli Toska, Anna Kostera-Pruszczyk, HyeJin Ra, Rup Tandan, Sotirios Papagiannopoulos, Natasha Willlems, Anne Mette Ostergaard Autzen, Meinoshin Okumura, Patrick Vermersch, Sarada Sakamuri, Maria Antonia Alberti Aguilo, Shigemi Shimose, Cynthia Carter, Ira Blount, Lisa Thompson, Maurer Pereira Martins, Richard Nowak, Hyung Seok Lee, Anna Kaminska, Joan Bratton, Nazire Pinar Acar, Junichi Ogasawara, Mohamed Mahdi-Rogers, Teiichiro Mitazaki, Marek Čierny, Craig Donahue, Jaya Trivedi, Neelam Goyal, Gonzalo Vidal, Brandy Quarles, Akiko Kanzaki, Yasuko Ikeda, Tomomi Kobashikawa, Morris Brown, Daisuke Yamamoto, Michel Deneve, Denis Korobko, Beth DiSanzo, Benedikt Schoser, Heidi Boterhoven, Eri Kobayashi, Maoko Shirane, Cristiani Fernanda Butinhao, Eriko Higuchi, Takashi Hayashi, Masanori Takahashi, Anne-Cécile Wielanek-Bachelet, Benjamin Rix Brooks, Emanuela Onesti, Tahseen Mozaffar, Liang Lu, Sevasti Bostantzopoulou, Christophe Vial, Shawn J. Bird, Sandi Mumfrey-Thomas, Julie Khoury, Kara Patrick, Kenichi Tsukita, Yoshiko Sano, Hiroshi Nakazora, David P. Richman, Gavin Brown, Yoon-Ho Hong, Tomohiro Kawamura, Igor Dias Brockhausen, Ye Liu, Acary Souza Bulle Oliveira, Soichiro Funaka, Tomoya Hasuike, Frank Lin, Luis Antonio Querol Gutierrez, Namita Goyal, Elena Pinzan, Michelle Mellion, Silvia Messina, Christopher Lindberg, Csilla Rozsa, J. Chad Hoyle, Yoko Kaneko, Gustavo Duran, Francesco Patti, Arshira Seddigh, Ele Kim Perez, Jayashri Srinivasan, Michael Benatar, Philip Van Damme, Salma Akhter, Daniel Ambrosio, Maria Salvado, Floyd Jones, Mark Sivak, Anneke J. van der Kooi, Karen Callison, Catherine Nigro, Rebekah Garcia, Thomas Arnold, Hideki Arima, Brigid Crabtree, Mary Varghese, Aditya Kumar, Miri Kim, Fanny O'Brien, Naya McKinnon, Lauren Wheeler, Hong Vu, Shunsuke Yoshimura, Masatoshi Omoto, Jeffrey T. Guptill, Maria Gabriele, Francoise Bouhour, Veena Mathew, Ritsu Nakayama, Rosa Hasan, Francesco Saccà, Mohammed Salajegheh, Diana Dimitrova, Alzira Alves de Siqueira Carvalho, Maurizio Inghilleri, George Sachs, Rekha Pillai, Enrico Marano, Monika Konyane, Anh Tran, Seda Aydinlik, Kendrick Henderson, Fumie Meguro, Alexandre Guerreiro, Amaiak Chilingaryan, Tiyonnoh Cash, Jun Kawamata, Julie Steele, Helene Gervais-Bernard, Thomas Harbo, Alejandra Dalila Garcia, Musa Kazim Onar, Sabrina Sacconi, Carlos Casasnovas Pons, Nadezhda Malkova, Denis Sazonov, Mireya Fernandez-Fournier, Karin Fricke, Laurie Gutmann, Amy Saklad, Clara Schommer, Sandra Taber, Fiona Norwood, Tugce Kirbas Cavdar, Monique Miesen, Fernanda Troili, Masanori Watanabe, Ratna Bhavaraju-Sanka, Ted M. Burns, Sari Atula, Faisal Sohail, Barbora Kurkova, Brigitta Szabadosne, Luciana Renata Cubas Volpe, Jane Pedersen, Jing Jing Wang, Masashi Inoue, Antonella Di Pasquale, Megan Kramer, Magda Chmelikova, Mehran Soltani, Tuan Vu, Laura Fionda, Eliz Agopian, Susan Shin, Anthony A. Amato, Lotte Vinge, Hakan Cavus, Gil I. Wolfe, Joan Nye, Delphine Mahieu, Miguel Wilken, Markus Färkkilä, Catherine Faber, Erin Manning, Emiko Tsuda, Rami Massie, Paolo Emilio Alboini, Yasmeen Shabbir, Angela Campanella, Aikaterini Dimitriou, Marcelo Rugiero, Cynthia Bodkin, Gyorgyi Szabo, Sharon Halton, Akshay Shah, Yasuko Maeda, Hans D. Katzberg, Yagmur Caliskan, Jaimin Shah, Katsuhisa Masaki, Valentina Damato, Blanka Andersson, Aline de Cassia Santos, Masahiro Mori, Renato Mantegazza, Misa Shimpo, Joanne Nemeth, Livia Dezsi, Anna De Rosa, Doreen Ho, Julie Moutarde, Efstathia Mitropoulou, Amy Woodall, Angela Micheels, László Vécsei, Byoung Joon Kim, Lisa Smith, Tomihiro Imai, Harpreet Kaur, Lorenzo Maggi, Jane Distad, Anita Mogensen, Ericka Simpson, Anne Cooley, Eliana Reyes, Ha Young Shin, Da Yoon Koh, Stefan Gingele, Susan Strom, Ezgi Yilmaz, Manisha Chopra, Anna Melnikova, Edouard Millois, Ludwig Gutmann, Miriam Freimer, Hirokazu Shinozaki, Heena Olalde, Kerry Naunton, Shunya Nakane, Ihsan Sengun, Dimos-Dimitrios Mitsikostas, Edina Varga, Juha-Pekka Erälinna, Wolfgang Löscher, Jan De Bleecker, Elena Bravver, Ana Lazaro, Eun Bin Cho, Thomas Cochrane, Jonathan Goldstein, Lisa D. Hobson-Webb, Michaela Tyblova, Angela Marsil, J. Edward Hartmann, Miyuki Morikawa, Karen Zakalik, Claude Desnuelle, Iveta Novakova, Michiaki Koga, Melinda Horvath, Luiz Otavio Maia Gonçalves, Elena Cortes Vicente, Alejandro Tobon Gonzalez, Stanley H. Appel, Brian Minton, Daniele Orrico, Brian Droker, Jacob Kaufman, Erica Coelho, Chafic Karam, Mikko Laaksonen, Katherine Amato, Jinmyoung Seok, Natalia Prando, Pauline Lahaut, Kaori Osakada, Phillipa Lamont, Alexandros Tselis, Daiane da Cruz Pacheco, Joan Højgaard, Hirokazu Shiraishi, Josef Bednarik, Stefania Morino, Mark Levine-Weinberg, Sara-Claude Michon, Yusuke Fukuda, Michael Pulley, Koichi Narikawa, Ricardo Rojas Garcia, Betsy Mosmiller, James Gilchrist, Maria da Penha Morita Ananias, Maryanne Burdette, Shingo Konno, Janelle Butters, Stephan Wenninger, Debbie Davies, Thomas Skripuletz, Mohammad Alsharabati, Katarina Reguliova, Gabor Lovas, Yuichiro Gondo, Miju Shin, HyeLim Lee, Bruno Bezerra Rosa, Michael D. Weiss, Martha Zampaki, Andrea Caramma, Jeffrey V. Rosenfeld, Cigdem Ozen Aydin, Shara Holzberg, Hélène Merle, Olga Zapletalova, Kurt-Wolfram Suehs, Robert P. Lisak, Dale J. Lange, Albert Hietala, Sedat Sen, Elena Giacomelli, Akiyuki Uzawa, Tomás Augusto Suriane Fialho, Matteo Garibaldi, Nadia Sattar, Wai-Kuen Leong, Lindsay Kaplan, Tetsuya Kanai, Jaana Eriksson, Akiko Nagaishi, Khema Sharma, Tamar Gibson, Mohamed Kazamel, Yulia Nesterova, Sascha Alvermann, Murat Terzi, Taylor Darnell, Donna Carnes, Victor Balyazin, John T. Kissel, Waqar Waheed, Jana Junkerova, Kimberly Robeson, Nicholas Vlaikidis, Nicholas Silvestri, Fredrik Piehl, Maurício André Gheller Friedrich, Shun Shimohama, Nuria Vidal, Eleni Kasioti, H. James Jones, Michael K. Hehir, Luiz Augusto da Silva, Dave Watling, Leslie Roberts, Casey Faigle, Caroline Hourquin, Olli Oksaranta, Tomomi Imamura, Shin Hisahara, Dennis Jeffery, Marie-Hélène Soriani, M. Kawai, Chieko Yoshikawa, Roseann Keo, Angela Genge, Michelangelo Maestri Tassoni, Milvia Pleitez, Michael H. Rivner, Maki Jingu, Giorgia Puorro, Andrea Swenson, Saiju Jacob, Carolina Ortea, Shuichiro Suzuki, Marguerite Engel, Ikuko Kamegamori, SangAe Park, Guilhem Sole, Lesly Welsh, Nichole Gallatti, Jakit Gollogly, Daniel Jons, Yasuteru Sano, Takuya Matsushita, Omar Khan, Maria Cristina Gori, Thabata Veiga, Julie Agriesti, Jos Maessen, Sandra Guinrich, Francesca Bevilacqua, Laura Haar, Jordana Gonçalves Geraldo, Justin Y. Kwan, Hidekazu Suzuki, Dai Matsuse, Kelly Jia, Ozlem Tun, Lara Katzin, Yasushi Suzuki, Shannon Lucy, Carlo Antozzi, ANS - Neuroinfection & -inflammation, Neurology, Howard, James F, Utsugisawa, Kimiaki, Benatar, Michael, Murai, Hiroyuki, Barohn, Richard J, Illa, Isabel, Jacob, Saiju, Vissing, John, Burns, Ted M, Kissel, John T, Muppidi, Srikanth, Nowak, Richard J, O'Brien, Fanny, Wang, Jing-Jing, Mantegazza, Renato, Mazia, Claudio Gabriel, Wilken, Miguel, Ortea, Carolina, Saba, Juliet, Rugiero, Marcelo, Bettini, Mariela, Vidal, Gonzalo, Garcia, Alejandra Dalila, Lamont, Phillipa, Leong, Wai-Kuen, Boterhoven, Heidi, Fyfe, Beverly, Roberts, Leslie, Jasinarachchi, Mahi, Willlems, Natasha, Wanschitz, Julia, Löscher, Wolfgang, De Bleecker, Jan, Van den Abeele, Guy, de Koning, Kathy, De Mey, Katrien, Mercelis, Rudy, Wagemaekers, Linda, Mahieu, Delphine, Van Damme, Philip, Smetcoren, Charlotte, Stevens, Olivier, Verjans, Sarah, D'Hondt, Ann, Tilkin, Petra, Alves de Siqueira Carvalho, Alzira, Hasan, Rosa, Dias Brockhausen, Igor, Feder, David, Ambrosio, Daniel, Melo, Ana Paula, Rocha, Rosana, Rosa, Bruno, Veiga, Thabata, Augusto da Silva, Luiz, Gonçalves Geraldo, Jordana, da Penha Morita Ananias, Maria, Nogueira Coelho, Erica, Paiva, Gabriel, Pozo, Marina, Prando, Natalia, Dada Martineli Torres, Debora, Fernanda Butinhao, Cristiani, Coelho, Erica, Renata Cubas Volpe, Luciana, Duran, Gustavo, Gomes da Silva, Tamires Cristina, Otavio Maia Gonçalves, Luiz, Pazetto, Lucas Eduardo, Souza Duca, Luciana, Suriane Fialho, Tomás Augusto, Gheller Friedrich, Maurício André, Guerreiro, Alexandre, Mohr, Henrique, Pereira Martins, Maurer, da Cruz Pacheco, Daiane, Macagnan, Ana Paula, de Cassia Santos, Aline, Bulle Oliveira, Acary Souza, Amaral de Andrade, Ana Carolina, Annes, Marcelo, Cavalcante Lino, Valeria, Pinto, Wladimir, Miranda, Carolina, Carrara, Fernanda, Souza, Iandra, Genge, Angela, Massie, Rami, Campbell, Natasha, Bril, Vera, Katzberg, Han, Soltani, Mehran, Ng, Eduardo, Siddiqi, Zaeem, Phan, Celile, Blackmore, Derrick, Vohanka, Stanislav, Bednarik, Josef, Chmelikova, Magda, Cierny, Marek, Toncrova, Stanislava, Junkerova, Jana, Kurkova, Barbora, Reguliova, Katarina, Zapletalova, Olga, Pitha, Jiri, Novakova, Iveta, Tyblova, Michaela, Wolfova, Marcela, Jurajdova, Ivana, Andersen, Henning, Harbo, Thoma, Vinge, Lotte, Mogensen, Anita, Højgaard, Joan, Witting, Nanna, Autzen, Anne Mette, Pedersen, Jane, Färkkilä, Marku, Atula, Sari, Nyrhinen, Anne, Erälinna, Juha-Pekka, Laaksonen, Mikko, Oksaranta, Olli, Eriksson, Jaana, Harrison, Tuula, Desnuelle, Claude, Sacconi, Sabrina, Soriani, Marie-Hélène, Decressac, Sonia, Moutarde, Julie, Lahaut, Pauline, Solé, Guilhem, Le Masson, Gwendal, Wielanek-Bachelet, Anne-Cécile, Gaboreau, Morgane, Moreau, Caroline, Wilson, Amy, Vial, Christophe, Bouhour, Françoise, Gervais-Bernard, Helene, Merle, Hélène, Hourquin, Caroline, Lacour, Arnaud, Outteryck, Olivier, Vermersch, Patrick, Zephir, Hélène, Millois, Edouard, Deneve, Michel, Deruelle, Fabienne, Schoser, Benedikt, Wenninger, Stephan, Stangel, Martin, Alvermann, Sascha, Gingele, Stefan, Skripuletz, Thoma, Suehs, Kurt-Wolfram, Trebst, Corinna, Fricke, Karin, Papagiannopoulos, Sotirio, Bostantzopoulou, Sevasti, Vlaikidis, Nichola, Zampaki, Martha, Papadopoulou, Nikoletta, Mitsikostas, Dimos-Dimitrio, Kasioti, Eleni, Mitropoulou, Efstathia, Charalambous, Despoina, Rozsa, Csilla, Horvath, Melinda, Lovas, Gabor, Matolcsi, Judit, Szabo, Gyorgyi, Szabadosne, Brigitta, Vecsei, Laszlo, Dezsi, Livia, Varga, Edina, Konyane, Monika, Gross, Bella, Azrilin, Olga, Greenbereg, Nelly, Bali Kuperman, Hila, Antonini, Giovanni, Garibaldi, Matteo, Morino, Stefania, Troili, Fernanda, Di Pasquale, Antonella, Filla, Alessandro, Costabile, Teresa, Marano, Enrico, Sacca, Francesco, Marsili, Angela, Puorro, Giorgia, Maestri Tassoni, Michelangelo, De Rosa, Anna, Bonanno, Silvia, Antozzi, Carlo, Maggi, Lorenzo, Campanella, Angela, Angelini, Corrado, Cudia, Paola, Pegoraro, Valentina, Pinzan, Elena, Bevilacqua, Francesca, Orrico, Daniele, Bonifati, Domenico Marco, Evoli, Amelia, Alboini, Paolo Emilio, D'Amato, Valentina, Iorio, Raffaele, Inghilleri, Maurizio, Fionda, Laura, Frasca, Vittorio, Giacomelli, Elena, Gori, Maria, Lopergolo, Diego, Onesti, Emanuela, Gabriele, Maria, Patti, Francesco, Salvatore Caramma, Andrea, Messina, Silvia, Reggio, Ester, Caserta, Cinzia, Uzawa, Akiyuki, Kanai, Tetsuya, Mori, Masahiro, Kaneko, Yoko, Kanzaki, Akiko, Kobayashi, Eri, Masaki, Katsuhisa, Matsuse, Dai, Matsushita, Takuya, Uehara, Taira, Shimpo, Misa, Jingu, Maki, Kikutake, Keiko, Nakamura, Yumiko, Sano, Yoshiko, Nagane, Yuriko, Kamegamori, Ikuko, Fujii, Yuko, Futono, Kazumi, Tsuda, Tomoko, Saito, Yuka, Suzuki, Hidekazu, Morikawa, Miyuki, Samukawa, Makoto, Kamakura, Sachiko, Shiraishi, Hirokazu, Mitazaki, Teiichiro, Motomura, Masakatsu, Mukaino, Akihiro, Yoshimura, Shunsuke, Asada, Shizuka, Kobashikawa, Tomomi, Koga, Megumi, Maeda, Yasuko, Takada, Kazumi, Takada, Mihoko Takada, Yamashita, Yumi, Yoshida, Seiko, Suzuki, Yasushi, Akiyama, Tetsuya, Narikawa, Koichi, Tsukita, Kenichi, Meguro, Fumie, Fukuda, Yusuke, Sato, Miwako, Matsuo, Hidenori, Fukudome, Takayasu, Gondo, Yuichiro, Maeda, Yasuhiro, Nagaishi, Akiko, Nakane, Shunya, Okubo, Yoshinori, Okumura, Meinoshin, Funaka, Soichiro, Kawamura, Tomohiro, Makamori, Masayuki, Takahashi, Masanori, Hasuike, Tomoya, Higuchi, Eriko, Kobayashi, Hisako, Osakada, Kaori, Taichi, Namie, Tsuda, Emiko, Hayashi, Takashi, Hisahara, Shin, Imai, Tomihiro, Kawamata, Jun, Murahara, Takashi, Saitoh, Masaki, Shimohama, Shun, Suzuki, Shuichiro, Yamamoto, Daisuke, Konno, Shingo, Imamura, Tomomi, Inoue, Masashi, Murata, Mayumi, Nakazora, Hiroshi, Nakayama, Ritsu, Ikeda, Yasuko, Ogawa, Miki, Shirane, Maoko, Kanda, Takashi, Kawai, Motoharu, Koga, Michiaki, Ogasawara, Junichi, Omoto, Masatoshi, Sano, Yasuteru, Arima, Hideki, Fukui, Sachie, Shimose, Shigemi, Shinozaki, Hirokazu, Watanabe, Masanori, Yoshikawa, Chieko, van der Kooi, Anneke, de Visser, Marianne, Gibson, Tamar, Maessen, Jo, de Baets, Marc, Faber, Catherine, Keijzers, Maria Johanna, Miesen, Monique, Kostera-Pruszczyk, Anna, Kaminska, Anna, Kim, Byung-Jo, Lee, Chang Nyoung, Koo, Yong Seo, Seok, Hung Youl, Kang, Hoo Nam, Ra, Hyejin, Kim, Byoung Joon, Cho, Eun Bin, Lee, Hyelim, Min, Ju-Hong, Seok, Jinmyoung, Koh, Da Yoon, Kwon, Juyoung, Lee, Jieun, Park, Sangae, Hong, Yoon-Ho, Lim, Jae-Sung, Kim, Miri, Kim, Seung Min, Kim, Yool-hee, Lee, Hyung Seok, Shin, Ha Young, Hwang, Eun Bi, Shin, Miju, Sazonov, Deni, Yarmoschuk, Asya, Babenko, Larisa, Malkova, Nadezhda, Melnikova, Anna, Korobko, Deni, Kosykh, Evgeniya, Pokhabov, Dmitry, Nesterova, Yulia, Abramov, Vladislav, Balyazin, Victor, Casasnovas Pons, Carlo, Alberti Aguilo, Maria, Homedes-Pedret, Christian, Palacios, Natalia Julia, Lazaro, Ana, Diez Tejedor, Exuperio, Fernandez-Fournier, Mireya, Lopez Ruiz, Pedro, Rodriguez de Rivera, Francisco Javier, Salvado Figueras, Maria, Gamez, Josep, Salvado, Maria, Cortes Vicente, Elena, Diaz-Manera, Jordi, Querol Gutierrez, Lui, Rojas Garcia, Ricardo, Vidal, Nuria, Arribas-Ibar, Elisabet, Piehl, Fredrik, Hietala, Albert, Bjarbo, Lena, Lindberg, Christopher, Jons, Daniel, Andersson, Blanka, Sengun, Ihsan, Ozcelik, Pinar, Tuga, Celal, Ugur, Muzeyyen, Boz, Cavit, Altiparmak, Didem, Gazioglu, Sibel, Ozen Aydin, Cigdem, Erdem-Ozdamar, Sevim, Bekircan-Kurt, Can Ebru, Yilmaz, Ezgi, Acar, Nazire Pinar, Caliskan, Yagmur, Efendi, Husnu, Aydinlik, Seda, Cavus, Hakan, Semiz, Cansu, Tun, Ozlem, Terzi, Murat, Dogan, Baki, Onar, Musa Kazim, Sen, Sedat, Cavdar, Tugce Kirba, Norwood, Fiona, Dimitriou, Aikaterini, Gollogly, Jakit, Mahdi-Rogers, Mohamed, Seddigh, Arshira, Maier, Gal, Sohail, Faisal, Sathasivam, Sivakumar, Arndt, Heike, Davies, Debbie, Watling, Dave, Rivner, Michael, Hartmann, J. Edward, Quarles, Brandy, Smalley, Nicole, Amato, Anthony, Cochrane, Thoma, Salajegheh, Mohammed, Roe, Kristen, Amato, Katherine, Toska, Shirli, Wolfe, Gil, Silvestri, Nichola, Patrick, Kara, Zakalik, Karen, Katz, Jonathan, Miller, Robert, Engel, Marguerite, Bravver, Elena, Brooks, Benjamin, Plevka, Sarah, Burdette, Maryanne, Sanjak, Mohammad, Kramer, Megan, Nemeth, Joanne, Schommer, Clara, Juel, Vern, Guptill, Jeffrey, Hobson-Webb, Lisa, Beck, Kate, Carnes, Donna, Loor, John, Anderson, Amanda, Lange, Dale, Agopian, Eliz, Goldstein, Jonathan, Manning, Erin, Kaplan, Lindsay, Holzberg, Shara, Kassebaum, Nicole, Pascuzzi, Robert, Bodkin, Cynthia, Kincaid, John, Snook, Riley, Guinrich, Sandra, Micheels, Angela, Chaudhry, Vinay, Corse, Andrea, Mosmiller, Betsy, Ho, Doreen, Srinivasan, Jayashri, Vytopil, Michael, Ventura, Nichola, Scala, Stephanie, Carter, Cynthia, Donahue, Craig, Herbert, Carol, Weiner, Elaine, Mckinnon, Jonathan, Haar, Laura, Mckinnon, Naya, Alcon, Karan, Daniels, Kevin, Sattar, Nadia, Jeffery, Denni, Mckenna, Kaitlyn, Guidon, Amanda, David, William, Dheel, Christina, Levine-Weinberg, Mark, Nigro, Catherine, Simpson, Ericka, Appel, Stanley H, Lai, Eugene, Lay, Lui, Pleitez, Milvia, Halton, Sharon, Faigle, Casey, Thompson, Lisa, Sivak, Mark, Shin, Susan, Bratton, Joan, Jacobs, Daniel, Brown, Gavin, Bandukwala, Ibrez, Brown, Morri, Kane, Jennifer, Blount, Ira, Freimer, Miriam, Hoyle, J. Chad, Agriesti, Julie, Khoury, Julie, Marburger, Tessa, Kaur, Harpreet, Dimitrova, Diana, Mellion, Michelle, Sachs, George, Crabtree, Brigid, Keo, Roseann, Perez, Ele Kim, Taber, Sandra, Gilchrist, Jame, Andoin, Angela, Darnell, Taylor, Goyal, Neelam, Sakamuri, Sarada, So, Yuen T, Welsh, Lesly Welsh, Bhavaraju-Sanka, Ratna, Tobon Gonzalez, Alejandro, Jones, Floyd, Saklad, Amy, Nations, Sharon, Trivedi, Jaya, Hopkins, Steve, Kazamel, Mohamed, Alsharabati, Mohammad, Lu, Liang, Mumfrey-Thomas, Sandi, Woodall, Amy, Richman, David, Butters, Janelle, Lindsay, Molly, Mozaffar, Tahseen, Cash, Tiyonnoh, Goyal, Namita, Roy, Gulmohor, Mathew, Veena, Maqsood, Fatima, Minton, Brian, Jones, H. Jame, Rosenfeld, Jeffrey, Garcia, Rebekah, Garcia, Sonia, Echevarria, Laura, Pulley, Michael, Aranke, Shachie, Berger, Alan Ro, Shah, Jaimin, Shabbir, Yasmeen, Smith, Lisa, Varghese, Mary, Gutmann, Laurie, Gutmann, Ludwig, Swenson, Andrea, Olalde, Heena, Hafer-Macko, Charlene, Kwan, Justin, Zilliox, Lindsay, Callison, Karen, Disanzo, Beth, Naunton, Kerry, Bilsker, Martin, Sharma, Khema, Reyes, Eliana, Cooley, Anne, Michon, Sara-Claude, Steele, Julie, Karam, Chafic Karam, Chopra, Manisha, Bird, Shawn, Kaufman, Jacob, Gallatti, Nichole, Vu, Tuan, Katzin, Lara, Mcclain, Terry, Harvey, Brittany, Hart, Adam, Huynh, Kristin, Beydoun, Said, Chilingaryan, Amaiak, Droker, Brian, Lin, Frank, Shah, Akshay, Tran, Anh, Akhter, Salma, Malekniazi, Ali, Tandan, Rup, Hehir, Michael, Waheed, Waqar, Lucy, Shannon, Weiss, Michael, Distad, Jane, Downing, Sharon, Strom, Susan, Lisak, Robert, Bernitsas, Evanthia, Khan, Omar, Kumar Sriwastava, Shitiz, Tselis, Alexandro, Jia, Kelly, Bertorini, Tulio, Arnold, Thoma, Henderson, Kendrick, Pillai, Rekha, Liu, Ye, Wheeler, Lauren, Hewlett, Jasmine, Vanderhook, Mollie, Dicapua, Daniel, Keung, Benison, Kumar, Aditya, Patwa, Huned, Robeson, Kimberly, Nye, Joan, Vu, Hong, Howard, J, Utsugisawa, K, Benatar, M, Murai, H, Barohn, R, Illa, I, Jacob, S, Vissing, J, Burns, T, Kissel, J, Muppidi, S, Nowak, R, O'Brien, F, Wang, J, Mantegazza, R, and Bonanno, S

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, Drug Resistance, Adult, Aged, Antibodies, Monoclonal, Humanized, Autoantibodies, Double-Blind Method, Female, Humans, Middle Aged, Myasthenia Gravis, Receptors, Cholinergic, Outcome Assessment (Health Care), Severity of Illness Index, Neurology (clinical), law.invention, Complement inhibitor, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, Receptors, Clinical endpoint, Humanized, Cholinergic, education.field_of_study, Eculizumab, Autoantibodie, Myasthenia Gravi, Settore MED/26 - NEUROLOGIA, Human, medicine.drug, Meningitides, medicine.medical_specialty, Population, Placebo, Antibodies, 03 medical and health sciences, Internal medicine, medicine, education, business.industry, Surgery, Thymectomy, 030104 developmental biology, business, 030217 neurology & neurosurgery
Abstract

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Published
2017
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48. OSMANLI DEVLETİNİN SON YÜZYILINDA MALATYA-TOKMA (TOHMA/TOKHMA) NEHRİ SUYU’NUN ARAZİ VE İÇME SUYUNDA KULLANIMI

Author

Sevim Erdem

Subjects
Malatya Sancağı,Tohma (Tokhma) Suyu,Meşrutiyet,Osmanlı Devleti, The Sanjak of Malatya,Tohma (Tokhma) water,constitutional monarchy,the Ottoman State, Social, Sosyal
Abstract

BugünküMalatya, tarihi süreç içerisinde birkaç defa yer değiştirmiş ve ilk olarakArslantepe ve çevresi yerleşim yeri olarak alınırken daha sonra Melitene adıverilen yer ikinci merkezi olmuş son değişimini ise Osmanlı Devleti zamanındaHafız Paşa’nın emri ile gerçekleştirmiş ve Aspuzu bağlarına yerleşmişlerdir.Malatyaönemli yolların kesiştiği noktada yer alır. Bilhassa Roma ve Bizansdönemlerinde doğu sınırlarının kontrolünün sağlanması açısından askeri biröneme sahip olmuştur. Şehir Cumhuriyet’in ilk yıllarında il merkezi konumunagelmiş ve bilhassa iki önemli demiryolu hattının şehre ulaşmasıyla hem mekânsalbüyüme hem de nüfus bakımında önemli bir artış sağlamıştır.XIX.Yüzyılda Avrupa başkentleri hızlı bir imar hamlesi yaşarken, bir yandan daşehirsel altyapılarını geliştirmeye çalışmışlardır. Bu değişim, su alanında dakendini göstermeye başlamıştır. Şehirlerde basınçlı su dağıtımının yapılmasınabaşlanmış. Suya olan ihtiyacın gün geçtikçe artması, devletin yeni yerleşimyerlerini açması, fabrikalaşma, sulu tarımın giderek daha yaygın hale gelmesi,suyun daha sistemli kullanımını gerekli kılmıştır. Osmanlı Devleti’nin sonyüzyılında verilen hizmetlerin büyük bir kısmı imtiyaz karşılığında yapılmayabaşlanmış, Tohma Suyunun da Meşrutiyet devrinde devlet ekonomisinekazandırılması için imtiyaza verildiği görülmüştür., The currentlocation of city of Malatya has changed several times throughout the history.The first site was Arslantepe neighbourhood which later changed to a secondsite, called Melinete. And finally, with the command of General Hafız, Asbuzu/Aspuzu vineyards became the last site for settlement.Malatya has alocation where important roads cross. Therefore, it has kept its importance asan important passageway route. Particulary in Byzantium and Roman periods, ithad a military significance in order to control the east border. Malatyaattained a central position in the first years of the Republic. As twoimportant railroads was connected to the city, there was a notable growth inthe city both physically and demographically.In the 19thcentury, there were rapid city development plans in European capitals alongwith the attempts to develop infrastructure of the cities. Such changes hadalso a reflection in the issue about drinking water. The distribution ofpressure water was started in the cities. The period of fountain water wasreplaced by a new period in which water was distributed to houses andworkplaces through taps. As the need for water increased day by day and the newsites, industrialization and irrigated farming became more and more widespread,it became compulsory to use the water systematically. In the last century ofOttoman Empire, most of services were given in exchange for privileges and itwas seen that Tohma water was also given for privilege in order to bring it instate economy in the period of constitutional monarchy.

Published
2017
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49. Identifying a Cut-off Point for Timed Up and Go Test in Neuromuscular Diseases.

Author

Demirci, Cevher Savcun, Sütçü, Gülşah, Ayvat, Fatma, Kılınç, Özge Onursal, Doğan, Mert, Ayvat, Ender, Kurt, Can Ebru Bekircan, Özdamar, Sevim Erdem, Yıldırı, Sibel Aksu, Kılınç, Muhammed, and Tan, Ersin

Subjects
NEUROMUSCULAR disease diagnosis, REFERENCE values, POSTURAL balance, NEUROMUSCULAR diseases, NEUROPSYCHOLOGICAL tests, RISK assessment, ACCIDENTAL falls, SENSITIVITY & specificity (Statistics), NEUROLOGIC examination
Abstract

Copyright of Turkish Journal of Neurology / Turk Noroloji Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2022
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50. Neuropathic pain frequency in neurology outpatients: A multicenter study

Author

Filiz Koç, Burcu Gökçe Çokal, Tahir Kurtuluş Yoldaş, Zeynep Ünlütürk, Melih Tutuncu, Can Ebru Bekircan-Kurt, Ersin Tan, Cavit Boz, Berin Inan, Mehmet Ali Akalin, Sevim Erdem-Ozdamar, Necdet Karli, Abdülcemal Özcan, Kayihan Uluc, Özden Kamışlı, İhsan Şükrü Şengün, Duygu Guner Ozcanyuz, Selda Keskin, Onur Bulut, Hafize Nalan Güneş, Burhanettin Uludag, Çağdaş Erdoğan, Pinar Kahraman-Koytak, and Ege Üniversitesi

Subjects
gabapentinoid, medicine.medical_specialty, Neurology, Turkish Version, business.industry, General Neuroscience, gabapentin, DN4, Reliability, Neuropathic pain, Validity, Psychiatry and Mental health, Impact, Multicenter study, painDETECT, Symptoms, Prevalence, Physical therapy, medicine, neuropathic pain treatment guidelines, pregabalin, business, Research Article
Abstract

[No Abstract Available], Peripheral Nerve Soc, Abdi Ibrahim Pharmaceuticals, This work was funded by Abdi Ibrahim Pharmaceuticals

Published
2020

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