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3. Synthesis of superficially modified Ce1−x(Zr + Y)xO2−δ solid solutions and thermogravimetric analysis of their performance in the catalytic soot combustion

Author

W N Téllez-Salazar, J A Fabián-Anguiano, O Ovalle-Encinia, B H Zeifert, A Ezeta-Mejía, I C Romero-Ibarra, and J Ortiz-Landeros

Subjects
CeO2, citrate-EDTA complexing method, co-doping, catalytic soot combustion, Fe2O3, Materials of engineering and construction. Mechanics of materials, TA401-492, Chemical technology, TP1-1185
Abstract

In this work, solid solutions of general formula Ce _1−x (Zr + Y)xO _2− _δ were chemically synthesized through the so-called citrate-EDTA complexing method, wherein the doping cations Zr and Y were substituted in the ceria lattice with an equimolar amount of 0.05 ≤ x ≤ = 0.25. The ternary oxides were heat-treated, and those that showed the best textural properties were superficially impregnated with Fe _2 O _3 particles by the thermal decomposition method using a metalorganic precursor. The X-ray diffraction results suggest that co-doping with Zr ^4+ and Y ^3+ promotes a slight distortion of the CeO _2 cubic cell. Nevertheless, the fluorite cubic structure of the oxides remains stable after being exposed to heat treatments. Furthermore, using scanning electron microscopy and Raman techniques, the presence of deposited Fe _2 O _3 and the formation of extrinsic vacancies in the materials could be corroborated. Finally, the oxides’ catalytic evaluation in the soot oxidation reaction was carried out using the thermogravimetry technique. The ternary oxide with cerium molar content equal to 0.9 and impregnated with Fe _2 O _3 presented excellent catalytic behavior for soot oxidation. T _10 , T _50 , and T _90 temperatures were 310, 383, and 416 °C, respectively.

Published
2021
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5. OCT Variability Prevents Their Use as Robust Biomarkers in Multiple Sclerosis

Author

Marta Para-Prieto, Juan F. Arenillas, Lisandro Cordero, Gloria Gonzalez Fernandez, Sara Crespo, Raul Martin, Laura Mena-Garcia, Andres Valisena, Jose-Carlos Pastor, and N. Téllez

Subjects
medicine.medical_specialty, genetic structures, Eye disease, Nerve fiber layer, Foveal thickness, Patient assessment, 03 medical and health sciences, 0302 clinical medicine, Ophthalmology, Medicine, Optic neuritis, Original Research, retinal nerve fiber layer, RNFL, variability, business.industry, Multiple sclerosis, Healthy subjects, Clinical Ophthalmology, medicine.disease, eye diseases, medicine.anatomical_structure, foveal thickness, FT, Clinical diagnosis, multiple sclerosis, MS, 030221 ophthalmology & optometry, spectral-domain optical coherence tomography, SD-OCT, sense organs, business, 030217 neurology & neurosurgery
Abstract

Marta Para-Prieto,1,2 Raul Martin,1,3,4 Sara Crespo,2 Laura Mena-Garcia,1 Andres Valisena,2 Lisandro Cordero,1 Gloria Gonzalez Fernandez,2 Juan F Arenillas,5 Nieves Tellez,5 Jose Carlos Pastor1,2 1Universidad de Valladolid, Instituto Universitario de Oftalmobiología Aplicada (IOBA Eye Institute), Valladolid, 47011, Spain; 2Hospital Clínico Universitario, Department of Ophthalmology, Valladolid, 47005, Spain; 3Universidad de Valladolid, Departamento de Física Teórica, Atómica y Óptica, Valladolid, 47011, Spain; 4Plymouth University, Faculty of Health and Human Sciences, Plymouth, UK; 5Hospital Clínico Universitario, Department of Neurology, Valladolid, 47005, SpainCorrespondence: Raul MartinIOBA Eye Institute, University of Valladolid, Paseo de Belen, 17, Valladolid, 47011, SpainTel +34 983 184 848Fax +34 983 184 762Email raul@ioba.med.uva.esObjective: To evaluate the agreement between the peripapillary retinal nerve fiber layer (pRNFL) and foveal thickness (FT) measurements among three different spectral domain-optical coherence tomography (SD-OCT) instruments in a sample of multiple sclerosis (MS) patients and a healthy age-matched control group.Methods: An observational cross-sectional study with three groups: healthy subjects and MS patients w/w a previous clinical diagnosis of optic neuritis (ON) was conducted. The pRNFL and FT were measured using three different SD-OCT instruments (OCT PRIMUS 200 and OCT CIRRUS 500 SD-OCT [Carl Zeiss Meditec] and OCT 3D 2000 [Topcon]).Results: Twenty eyes from 10 healthy subjects matched in age with MS patients without a previous history of eye disease and 62 MS eyes from 31 MS patients (29 eyes without history of ON and 33 eyes with history of ON) were enrolled. Healthy subjects and MS patients without ON did not show differences between the pRNFL and FT thickness (P> 0.99) with any of the instruments. However, MS eyes with a previous episode of ON showed thinner pRNFL and FT (P< 0.01). PRIMUS and CIRRUS OCT showed better agreement of the pRNLF and FT in both healthy and MS eyes. However, 3D OCT showed less agreement in the pRNFL measurement with CIRRUS in both healthy and MS eyes.Interpretation: Although OCT is a valuable technology to improve MS patient assessment, differences between devices must be taken into account. It is necessary to create an international group that standardizes the measurement conditions and above all that provides reference bases for normal subjects.Keywords: spectral-domain optical coherence tomography; SD-OCT, multiple sclerosis; MS, retinal nerve fiber layer; RNFL, foveal thickness; FT, variability

Published
2021
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6. Frequency and Characterization of Movement Disorders in Anti-IgLON5 Disease

Author

Evelyn Berger-Sieczkowski, Gian Maria Asioli, Javier Villacieros-Álvarez, Katya Kotschet, Marcus Erdler, Joan Santamaria Cano, Carles Gaig, Teresa Montojo, Alejandro Herrero San Martin, Koldo Berganzo, Morten Blaabjerg, Günter U. Höglinger, Lydia Lopez Manzanares, Giuseppe Plazzi, Josep Dalmau, Thomas Seifert-Held, Maja Patalong-Ogiewa, Barbara Willekens, Federica Provini, Nicola Tambasco, Herburg Liendl, Yaroslau Compta, Jan Lewerenz, Ángela Milán-Tomás, Christian Geis, Alex Iranzo, Inmaculada Puertas, Caroline Giordana, Birgit Högl, Lidia Sabater, Antonio Martin-Bastida, Nora Möhn, Lucio Huebra, Sonia Quintas, Francesc Graus, Pasquale Nigro, Norbert Brüggemann, Markus Hutterer, Maarten J. Titulaer, Maria Elena Erro, Stefan Macher, Florian Schoeberl, N. Téllez, Mateus Mistieri Simabukuro, Franziska S. Thaler, Juan Carlos Garcia-Monco, Jesus Perez Perez, Romana Höftberger, Caspar B Seitz, Anna Heidbreder, Carlos Morata, Yvette S Crijnen, Chen Fei Ng, Tarsis Farias, María José Martí, Gaig, Carle, Compta, Yaroslau, Heidbreder, Anna, Marti, Maria J, Titulaer, Maarten J, Crijnen, Yvette, Högl, Birgit, Lewerenz, Jan, Erro, María Elena, Garcia-Monco, Juan Carlo, Nigro, Pasquale, Tambasco, Nicola, Patalong-Ogiewa, Maja, Erdler, Marcu, Macher, Stefan, Berger-Sieczkowski, Evelyn, Höftberger, Romana, Geis, Christian, Hutterer, Marku, Milán-Tomás, Angela, Martin-Bastida, Antonio, Manzanares, Lydia Lopez, Quintas, Sonia, Höglinger, Günter U, Möhn, Nora, Schoeberl, Florian, Thaler, Franziska S, Asioli, Gian Maria, Provini, Federica, Plazzi, Giuseppe, Berganzo, Koldo, Blaabjerg, Morten, Brüggemann, Norbert, Farias, Tarsi, Ng, Chen Fei, Giordana, Caroline, Herrero-San Martín, Alejandro, Huebra, Lucio, Kotschet, Katya, Liendl, Herburg, Montojo, Teresa, Morata, Carlo, Perez, Jesus Perez, Puertas, Inmaculada, Seifert-Held, Thoma, Seitz, Caspar, Simabukuro, Mateus Mistieri, Tellez, Nieve, Villacieros-Álvarez, Javier, Willekens, Barbara, Sabater, Lidia, Iranzo, Alex, Cano, Joan Santamaria, Dalmau, Josep, and Graus, Francesc

Subjects
Dystonia, Pediatrics, medicine.medical_specialty, Ataxia, Movement disorders, business.industry, autoimmunity, Anti-IgLON5, neurodegeneration, Chorea, medicine.disease, Akathisia, nervous system diseases, medicine, Body region, Human medicine, Neurology (clinical), Myokymia, medicine.symptom, business, Myoclonus, Research Article
Abstract

Background and ObjectivesAnti-IgLON5 disease is a recently described neurologic disease that shares features of autoimmunity and neurodegeneration. Abnormal movements appear to be frequent and important but have not been characterized and are underreported. We describe the frequency and types of movement disorders in a series of consecutive patients with this disease.MethodsIn this retrospective, observational study, the presence and phenomenology of movement disorders were assessed with a standardized clinical questionnaire. Available videos were centrally reviewed by 3 experts in movement disorders.ResultsSeventy-two patients were included. In 41 (57%), the main reason for initial consultation was difficulty walking along with one or several concurrent movement disorders. At the time of anti-IgLON5 diagnosis, 63 (87%) patients had at least 1 movement disorder with a median of 3 per patient. The most frequent abnormal movements were gait and balance disturbances (52 patients [72%]), chorea (24 [33%]), bradykinesia (20 [28%]), dystonia (19 [26%]), abnormal body postures or rigidity (18 [25%]), and tremor (15 [21%]). Other hyperkinetic movements (myoclonus, akathisia, myorhythmia, myokymia, or abdominal dyskinesias) occurred in 26 (36%) patients. The craniofacial region was one of the most frequently affected by multiple concurrent movement disorders (23 patients [32%]) including dystonia (13), myorhythmia (6), chorea (4), or myokymia (4). Considering any body region, the most frequent combination of multiple movement disorders consisted of gait instability or ataxia associated with craniofacial dyskinesias or generalized chorea observed in 31 (43%) patients. In addition to abnormal movements, 87% of patients had sleep alterations, 74% bulbar dysfunction, and 53% cognitive impairment. Fifty-five (76%) patients were treated with immunotherapy, resulting in important and sustained improvement of the movement disorders in only 7 (13%) cases.DiscussionMovement disorders are a frequent and leading cause of initial neurologic consultation in patients with anti-IgLON5 disease. Although multiple types of abnormal movements can occur, the most prevalent are disorders of gait, generalized chorea, and dystonia and other dyskinesias that frequently affect craniofacial muscles. Overall, anti-IgLON5 disease should be considered in patients with multiple movement disorders, particularly if they occur in association with sleep alterations, bulbar dysfunction, or cognitive impairment.

Published
2021
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7. 13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (II)

Author

O, Fernández, X, Montalban, Y, Aladro, A, Alonso, R, Arroyo, C, Calles, T, Castillo-Triviño, M, Comabella, L, Costa-Frossard, L, Forero, R, Ginestal, L, Landete, M, Llaneza, S, Llufriu, M L, Martínez-Ginés, J, Meca-Lallana, M, Mendibe, C, Oreja-Guevara, A, Oterino, J M, Prieto, Ll, Ramió-Torrentà, L, Romero-Pinel, N, Téllez, and A, Rodríguez-Antigüedad

Subjects
Multiple Sclerosis, Humans, Congresses as Topic, Child
Abstract

For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS.This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020.This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed.Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS.XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II).Introducción. Desde hace más de una década, tras el Congreso ECTRIMS, se celebra en España la reunión post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) se reúnen para revisar las novedades presentadas en el ECTRIMS. Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias de la reunión post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 virtualmente. Desarrollo. En esta segunda parte se destaca la importancia del género y la edad en la compresión de la patología de la enfermedad y la optimización de su manejo. Se exponen los avances realizados en la EM pediátrica desde un punto de vista neuropsicológico y de neuroimagen. Por su parte, cobran especial protagonismo los hallazgos que contribuyen a realizar un enfoque del tratamiento más personalizado y a elegir la mejor estrategia de tratamiento (farmacológica y no farmacológica) para cada paciente. De igual forma, se abordan los resultados relacionados con las estrategias posibles que promuevan la remielinización. Aunque no hay grandes avances en el tratamiento de formas progresivas, se destacan algunos métodos cuantitativos para la clasificación de estos pacientes. Además, se incluyen los resultados sobre herramientas potenciales de evaluación y tratamiento de los déficits cognitivos, y algunos aspectos relevantes observados en el espectro de los trastornos de la neuromielitis óptica. Por último, se detallan los resultados de las ponencias consideradas como noticias de última hora en el ECTRIMS-ACTRIMS. Conclusiones. Se presentaron avances principalmente sobre el conocimiento de la EM pediátrica, las estrategias de remielinización y la evaluación cognitiva en la EM.

Published
2021

8. 12th Post-ECTRIMS Meeting: review of the novelties from the 2019 ECTRIMS Congress (II)

Author

O, Fernández, Y, Aladro, R, Arroyo, Ll, Brieva, M C, Calles-Hernández, P, Carrascal, M, Comabella, L, Costa-Frossard, S, Eichau, J A, García-Merino, R, Ginestal, I, González, G, Izquierdo, M L, Martínez-Ginés, J E, Meca-Lallana, M M, Mendibe-Bilbao, A, Oterino, J M, Prieto, J, Río, Ll, Ramió-Torrentà, L, Romero-Pinel, N, Téllez, and A, Rodríguez-Antigüedad

Subjects
Pregnancy Complications, Biomedical Research, Multiple Sclerosis, Pregnancy, Humans, Female, Congresses as Topic
Abstract

Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting.To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts.In this second part, the most recent evidence on the use of disease-modifying treatments during pregnancy is presented. Details are provided concerning the results of phase 3 clinical trials conducted to evaluate the efficacy and safety of two potential disease-modifying treatments for relapsing-remitting multiple sclerosis: ponesimod and ofatumumab. For the progressive forms, both available disease modifying treatments and others still in the research phase are reviewed. In the field of stem cell therapies, the article includes the results of the only clinical trial carried out to date comparing patients with relapsing-remitting multiple sclerosis treated with autologous haematopoietic stem cell transplantation and those treated with disease-modifying therapies. There are no important developments as regards symptomatic treatments, although the European Academy of Neurology has published a guide on palliative care. The various sources of information that collect pharmacovigilance data in the post-marketing setting are reviewed.Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available.XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (II).Introducción. Como cada año, tras la celebración del Congreso del ECTRIMS, reconocidos neurólogos españoles expertos en esclerosis múltiple expusieron en la Reunión Post-ECTRIMS las principales novedades en investigación en este ámbito. Objetivo. Sintetizar el contenido presentado en la XII edición de la Reunión Post-ECTRIMS, que tuvo lugar en septiembre de 2019 en Sevilla y que se presenta en dos partes. Desarrollo. En esta segunda parte, se exponen las evidencias más recientes sobre el uso de tratamientos modificadores de la enfermedad durante el embarazo. Se detallan los resultados de ensayos clínicos en fase 3 en los que se ha evaluado la eficacia y la seguridad de dos potenciales tratamientos modificadores de la enfermedad para la esclerosis múltiple remitente recurrente: ponesimod y ofatumumab. Para las formas progresivas, se revisan los tratamientos modificadores de la enfermedad disponibles y en investigación. En el ámbito de las terapias con células madre, se incluyen los resultados del único ensayo clínico hasta la fecha que compara a pacientes con esclerosis múltiple remitente recurrente tratados con trasplante autólogo de células madre hematopoyéticas y a los tratados con tratamientos modificadores de la enfermedad. No hay grandes novedades sobre tratamientos sintomáticos, aunque la Academia Europea de Neurología ha publicado una guía sobre cuidados paliativos. Se revisan las distintas fuentes de información que recogen datos de farmacovigilancia en el entorno poscomercialización. Conclusiones. Los pacientes diagnosticados en los últimos años tienden a tener una menor gravedad de la esclerosis múltiple, probablemente debido al diagnóstico desde sus estadios más leves y al continuo aumento de tratamientos disponibles.

Published
2020

9. Citotoxicidad de metabolitos secundarios de algunas plantas colombianas

Author

Alba N. Téllez, Clemencia De Castro, Tulia Riveros de Murcia, Andrea Alvarado, Luz Mary Mendoza, Julio Pedrozo, and Rubén Torrenegra

Subjects
General Earth and Planetary Sciences, General Environmental Science
Abstract

En un estudio preliminar para evaluar el potencial citotóxico de los metabolitos de doce plantas colombianas, se analizaro los metabolitos de los géneros Ageratina, Pentacalia, Curatela, Espeletia, Ageratina y Stemmadenia. Los resultados obtenidos muestran que los compuestos jacaranona y acetato de longipilina presentaron el mayor potencial citotóxico a bajas concentraciones, 4 μg/mL.

Published
2017
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10. Clinical manifestations of the anti-IgLON5 disease

Author

Josep Dalmau, Caroline Giordana, Maria J. Martí, Lidia Sabater, Mateus Mistieri Simabukuro, Joan Santamaria, Luis Bataller, N. Téllez, Katya Kotschet, Norbert Brüggemann, Inmaculada Puertas, Jan Lewerenz, Klaus-Peter Wandinger, Carles Gaig, Birgit Högl, Teresa Montojo, Francesc Graus, Jesus Pérez-Pérez, Stefan Macher, Guadalupe Ercilla, A. Iranzo, Yarko Compta, Anna Heidbreder, and Caspar Seitz

Subjects
Sleep Wake Disorders, 0301 basic medicine, medicine.medical_specialty, Cell Adhesion Molecules, Neuronal, Population, Excessive daytime sleepiness, Autoimmune Diseases, Progressive supranuclear palsy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Cognitive decline, education, Aged, Autoantibodies, Retrospective Studies, Aged, 80 and over, education.field_of_study, Sleep disorder, business.industry, Brain, Sleep apnea, Chorea, Parasomnia, Middle Aged, medicine.disease, 030104 developmental biology, Immunoglobulin G, Immunotherapy, Neurology (clinical), medicine.symptom, Carrier Proteins, business, Biomarkers, 030217 neurology & neurosurgery, HLA-DRB1 Chains
Abstract

Objective:To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies.Methods:This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques.Results:Patients' median age was 64 years (range 46–83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16.Conclusions:Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.

Published
2017
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11. Immune Tolerance in Multiple Sclerosis and Neuromyelitis Optica with Peptide-Loaded Tolerogenic Dendritic Cells in a Phase 1b Trial

Author

Sara Llufriu, Bonaventura Casanova, Pablo Villoslada, Gemma Vila, N. Téllez, Daniel Benitez-Ribas, Miquel Lozano, Raquel Cabezón, Nuria Sola-Valls, Marisa Martinez Gines, Yolanda Blanco, Irene Pulido-Valdeolivas, Lawrence Steinman, Magi Andorra, Joan Cid, Carolina España, Marta Español, Albert Saiz, Maria Sepúlveda, Elena H. Martinez-Lapiscina, Irati Zubizarreta, Georgina Flórez-Grau, Manel Juan, Celia Oreja-Guevara, and Esteve Trias

Subjects
Adult, Male, immune tolerance, Multiple Sclerosis, Medical Sciences, Regulatory T cell, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Cell- and Tissue-Based Therapy, T cells, neuromyelitis optica, Antígens, multiple sclerosis, T-Lymphocytes, Regulatory, Dendritic cells, Immune tolerance, Antigen, Clinical endpoint, Humans, Medicine, Antigens, Cells, Cultured, Aquaporin 4, Multidisciplinary, Neuromyelitis optica, biology, business.industry, Multiple sclerosis, Neuromyelitis Optica, Tr1 cells, Dendritic Cells, Middle Aged, Biological Sciences, medicine.disease, Recombinant Proteins, Interleukin-10, medicine.anatomical_structure, PNAS Plus, Tolerability, Cèl·lules T, Cèl·lules dendrítiques, Immunology, biology.protein, Female, Immunotherapy, Antibody, business, Myelin Proteins
Abstract

Significance Application of antigen-specific immune tolerance in autoimmune disease is a long-sought goal. We studied diseases with abundant information on the autoimmune target: in multiple sclerosis (MS), various myelin antigens are known targets of T cells and antibodies, whereas in neuromyelitis optica (NMO), the aquaporin-4 channel is attacked by T cells and antibodies. We tested whether engineered dendritic cells might induce a tolerogenic immune response in these two conditions. In this in-human clinical study, individual regulatory T cells, secreting IL-10, a key tolerogenic cytokine, were detected after treatment. These results might lead to more extensive trials with this approach in autoimmune conditions where the antigenic target has been identified, including MS, NMO, myasthenia gravis, and Graves disease., There are adaptive T-cell and antibody autoimmune responses to myelin-derived peptides in multiple sclerosis (MS) and to aquaporin-4 (AQP4) in neuromyelitis optica spectrum disorders (NMOSDs). Strategies aimed at antigen-specific tolerance to these autoantigens are thus indicated for these diseases. One approach involves induction of tolerance with engineered dendritic cells (tolDCs) loaded with specific antigens. We conducted an in-human phase 1b clinical trial testing increasing concentrations of autologous tolDCs loaded with peptides from various myelin proteins and from AQP4. We tested this approach in 12 patients, 8 with MS and 4 with NMOSD. The primary end point was the safety and tolerability, while secondary end points were clinical outcomes (relapses and disability), imaging (MRI and optical coherence tomography), and immunological responses. Therapy with tolDCs was well tolerated, without serious adverse events and with no therapy-related reactions. Patients remained stable clinically in terms of relapse, disability, and in various measurements using imaging. We observed a significant increase in the production of IL-10 levels in PBMCs stimulated with the peptides as well as an increase in the frequency of a regulatory T cell, known as Tr1, by week 12 of follow-up. In this phase 1b trial, we concluded that the i.v. administration of peptide-loaded dendritic cells is safe and feasible. Elicitation of specific IL-10 production by peptide-specific T cells in MS and NMOSD patients indicates that a key element in antigen specific tolerance is activated with this approach. The results warrant further clinical testing in larger trials.

Published
2019

12. XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I)

Author

L Forero, M Mendibe, L. Landete, Manuel Comabella, Ll. Ramió-Torrentà, A Oterino, Celia Oreja-Guevara, R. Arroyo, Oscar Fernandez, N. Téllez, Alfredo Rodríguez-Antigüedad, Yolanda Aladro, M L Martínez-Ginés, J.M. Prieto, Xavier Montalban, M. Llaneza, A. Alonso, Tamara Castillo-Triviño, Sara Llufriu, Lucienne Costa-Frossard, R Ginestal, Carmen Calles, L Romero-Pinel, and José Meca-Lallana

Subjects
Age and gender, Medical education, 2019-20 coronavirus outbreak, Neuropsychology, MEDLINE, Treatment strategy, Cognition, Neurology (clinical), General Medicine, Cognitive Assessment System, Environmental exposure, Psychology
Abstract

Introduction For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. Aim This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020. Development This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed. Conclusions Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS.

Published
2021
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13. XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (I)

Author

R. Arroyo, Oscar Fernandez, Yolanda Aladro, A. Alonso, Lucienne Costa-Frossard, M Mendibe, L. Landete, L Forero, José Meca-Lallana, Agustín Oterino, Lluís Ramió-Torrentà, Celia Oreja-Guevara, L Romero-Pinel, J.M. Prieto, N. Téllez, Xavier Montalban, M. Llaneza, M L Martínez-Ginés, Sara Llufriu, C. Calles, Alfredo Rodríguez-Antigüedad, R Ginestal, Tamara Castillo-Triviño, and Manuel Comabella

Subjects
medicine.medical_specialty, High prevalence, Rehabilitation, business.industry, medicine.medical_treatment, Multiple sclerosis, General Medicine, Disease, medicine.disease, Cortical pathology, Clinical Practice, medicine, Neurology (clinical), business, Psychiatry, Cognitive impairment, Health needs
Abstract

INTRODUCTION: Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM: To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT: This first part addresses the latest studies on vitamin D deficiency and the discrepancies that currently exist regarding its treatment. The advances made in epigenetics allow us to present this approach as a possible biomarker of multiple sclerosis. An account is provided to explain the growing importance of imaging techniques to detect atrophy and other phenomena that occur during the disease, such as changes in iron concentration or remyelination processes, which allow us to further our understanding of the mechanisms of cortical pathology, and the dimensionality of neurodegeneration during its course. Findings related to immunological mechanisms and advances in potential antigen-specific therapies are discussed. The contribution presents the latest studies on the assessment of cognitive impairment and its rehabilitation, which are becoming increasingly important due to the high prevalence of these disorders and the absence of their systematic assessment in clinical practice. Finally, the unmet social and health needs of multiple sclerosis patients in our country are presented, with emphasis on the current deficits in the system of social protection.

Published
2020
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14. XII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2019 (II)

Author

N. Téllez, Alfredo Rodríguez-Antigüedad, Guillermo Izquierdo, M M Mendibe-Bilbao, M L Martínez-Ginés, L Romero-Pinel, R Ginestal, Ll Brieva, Yolanda Aladro, Lucienne Costa-Frossard, José Meca-Lallana, I González, J.M. Prieto, M C Calles-Hernandez, Oscar Fernandez, José Antonio del Río, J.A. García-Merino, P Carrascal, S. Eichau, A Oterino, R. Arroyo, Ll. Ramió-Torrentà, and Manuel Comabella

Subjects
medicine.medical_specialty, Palliative care, business.industry, Multiple sclerosis, MEDLINE, General Medicine, medicine.disease, Ofatumumab, Transplantation, Clinical trial, chemistry.chemical_compound, chemistry, Ponesimod, Pharmacovigilance, medicine, Neurology (clinical), Intensive care medicine, business, medicine.drug
Abstract

INTRODUCTION Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting. AIM To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts. DEVELOPMENT In this second part, the most recent evidence on the use of disease-modifying treatments during pregnancy is presented. Details are provided concerning the results of phase 3 clinical trials conducted to evaluate the efficacy and safety of two potential disease-modifying treatments for relapsing-remitting multiple sclerosis: ponesimod and ofatumumab. For the progressive forms, both available disease modifying treatments and others still in the research phase are reviewed. In the field of stem cell therapies, the article includes the results of the only clinical trial carried out to date comparing patients with relapsing-remitting multiple sclerosis treated with autologous haematopoietic stem cell transplantation and those treated with disease-modifying therapies. There are no important developments as regards symptomatic treatments, although the European Academy of Neurology has published a guide on palliative care. The various sources of information that collect pharmacovigilance data in the post-marketing setting are reviewed. CONCLUSIONS Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available.

Published
2020
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15. Netrin‐1 and multiple sclerosis: a new biomarker for neuroinflammation?

Author

Isabel Gallardo, Beatriz Gutiérrez, María Luisa Nieto, Patricia Mulero, N. Téllez, Rubén Martín, Claudia Cordova, Juan Carlos Muñoz, N. Redondo, Marita Hernández, Instituto de Salud Carlos III, Junta de Castilla y León, European Commission, Ministerio de Ciencia e Innovación (España), Mulero, Patricia [0000-0001-8716-8997], Nieto, María Luisa [0000-0001-6842-799X], Mulero, Patricia, and Nieto, María Luisa

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, animal structures, medicine.medical_treatment, Central nervous system, Enzyme-Linked Immunosorbent Assay, Mice, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Immune system, Recurrence, Cerebellum, Internal medicine, medicine, Animals, Humans, Neuroinflammation, Aged, Inflammation, Tumor Necrosis Factor-alpha, business.industry, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Middle Aged, Netrin-1, medicine.disease, Mice, Inbred C57BL, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Endocrinology, Spinal Cord, nervous system, Neurology, embryonic structures, Immunology, Biomarker (medicine), Female, Tumor necrosis factor alpha, Neurology (clinical), business, Biomarkers, 030217 neurology & neurosurgery
Abstract

[Background and purpose] Netrin‐1, an axon guidance protein, reduces serum levels of pro‐inflammatory mediators and stabilizes the blood−brain barrier limiting the entrance of immune cells into the central nervous system. The aim was to investigate its presence in the experimental autoimmune encephalomyelitis (EAE) model and in multiple sclerosis (MS) patients with and without clinical activity., [Methods] Netrin‐1 levels were evaluated in EAE mouse tissues. Afterwards, serum netrin‐1 was cross‐sectionally quantified in 90 patients with different MS phenotypes and 30 control subjects. An additional group of 10 relapsing−remitting MS (RRMS) patients was longitudinally evaluated throughout a relapse (RRMSr) with an interval of 60 days. Tumour necrosis factor α (TNFα), a reference inflammatory cytokine, and netrin‐1 were quantified by enzyme‐linked immunosorbent assay., [Results] Experimental autoimmune encephalomyelitis mice showed significantly lower netrin‐1 levels and higher TNFα amounts in sera, spinal cord and cerebella than healthy control mice. MS patients showed significantly lower serum netrin‐1 levels than controls (511.62 ± 209.30 and 748.32 ± 103.24 pg/ml, respectively; P ≤ 0.005). The lowest protein levels were found in RRMSr, remaining significantly lower throughout the relapse. TNFα serum concentrations were higher in MS patients compared to controls, and negatively correlated with netrin‐1 levels (r = −0.3734, P ≤ 0.0001)., [Conclusions] Netrin‐1 decreased in EAE and in MS patients, mainly during relapse, suggesting an anti‐inflammatory role of netrin‐1. Further research should be performed in a larger cohort of patients to validate netrin‐1 as a biomarker of MS inflammatory activity., This study was supported by MINECO (grants SAF2012‐34460 and ISCIII‐PI080441). CC, BG and IG were supported by the FPI‐Junta de Castilla y León Program, Spain (FSE co‐funded).

Published
2017

16. Revisión de las novedades presentadas en el congreso ECTRIMS 2018: XI Reunión Post-ECTRIMS (I)

Author

M. Tintoré, M C Calles-Hernandez, P Carrascal, Ll. Ramió-Torrentà, Oscar Fernandez, Celia Oreja-Guevara, J.A. García-Merino, Ll Brieva, L Romero-Pinel, R. Arroyo, Guillermo Izquierdo, Agustín Oterino, M M Mendibe-Bilbao, N. Téllez, José Meca-Lallana, Alfredo Rodríguez-Antigüedad, M L Martínez-Ginés, Manuel Comabella, C Arnal-Garcia, Yolanda Aladro, Lucienne Costa-Frossard, and Ana Saiz

Subjects
Neurology (clinical), General Medicine
Abstract

La reunion Post-ECTRIMS se celebro por undecimo ano consecutivo el pasado octubre de 2018 en Madrid, con el objetivo de analizar los avances en esclerosis multiple destacados en el ultimo congreso anual ECTRIMS. Fruto de esta reunion, formada por los lideres de opinion en esclerosis multiple de ambito nacional, se presentan dos articulos de revision. En esta segunda parte, se incluye el creciente numero de evidencias que confirman la seguridad de la exposicion a los tratamientos modificadores de la enfermedad en mujeres que planifican un embarazo, y el efecto beneficioso de la lactancia, siempre y cuando la enfermedad no este muy activa. Se abordan los datos que muestran como la aplicacion de los criterios de McDonald de 2017 en poblacion pediatrica ha mejorado considerablemente el diagnostico en comparacion con los criterios anteriores. En cuanto a la esclerosis multiple progresiva, los resultados de los farmacos neuroprotectores son poco concluyentes, pero se proponen biomarcadores para mejorar la evaluacion de la respuesta terapeutica. Los estudios sobre tratamientos de reparacion de la mielina sugieren que la remielinizacion en la esclerosis multiple es posible. De igual manera, se exponen indicios favorables sobre el trasplante de celulas madre hematopoyeticas, siempre que se seleccione adecuadamente a los pacientes. Por otro lado, se revisan las similitudes y diferencias de las recomendaciones de las nuevas guias de practica clinica publicadas. Por ultimo, los resultados positivos de la rehabilitacion cognitiva y motora con el uso de las nuevas tecnologias vaticinan la incorporacion sistematica de estas herramientas en el tratamiento de la enfermedad en un futuro proximo.

Published
2019
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19. Primary progressive multiple sclerosis diagnostic criteria: a reappraisal

Author

Carmen Tur, Alan J. Thompson, Bruno Brochet, Frederik Barkhof, Xavier Montalban, David Miller, Ana Rovira, Chris H. Polman, M.M. Vellinga, Massimo Filippi, Jaume Sastre-Garriga, Z Khaleeli, Marco Rovaris, N. Téllez, Neurology, Radiology and nuclear medicine, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, Montalban, X, Sastre Garriga, J, Filippi, Massimo, Khaleeli, Z, Tellez, N, Vellinga, Mm, Tur, C, Brochet, B, Barkhof, F, Rovaris, M, Miller, Dh, Polman, Ch, Rovira, A, and Thompson, Aj

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Time Factors, Primary Progressive Multiple Sclerosis, Severity of Illness Index, Primary progressive, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Predictive Value of Tests, Severity of illness, medicine, Humans, Visual Pathways, Aged, Retrospective Studies, business.industry, Multiple sclerosis, Oligoclonal Bands, Brain, Retrospective cohort study, McDonald criteria, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Magnetic Resonance Imaging, Surgery, Europe, Cross-Sectional Studies, Spinal Cord, Neurology, Predictive value of tests, Cohort, Evoked Potentials, Visual, Female, Neurology (clinical), business, Algorithms
Abstract

The diagnostic criteria used in primary progressive (PP) and relapsing—remitting (RR) multiple sclerosis (MS) show substantial differences. This introduces complexity in the diagnosis of MS which could be resolved if these criteria could be unified in terms of the requirements for dissemination in space (DIS). The aim of this study was to assess whether a single algorithm may be used to demonstrate DIS in all forms of MS. Five sets of RRMS criteria for DIS were applied to a cohort of 145 patients with established PPMS (mean disease duration: 11 years — PPMS-1): C1: Barkhof—Tintoré (as in 2005 McDonald’s criteria); C2: Swanton et al. (as in JNNP 2006); C3: presence of oligoclonal bands plus two lesions (as in McDonald’s criteria); C4 and C5: a two-step approach was also followed (patients not fulfilling C1 or C2 were then assessed for C3). Two sets of PPMS criteria for DIS were applied: C6: Thompson et al. (as in 2001 McDonald’s criteria); C7: 2005 McDonald criteria. A second sample of 55 patients with less than 5 years of disease duration (PPMS-2) was also analysed using an identical approach. For PPMS-1/PPMS-2, fulfilment was: C1:73.8%/66.7%; C2:72.1%/59.3%; C3:89%/79.2%; C4:96%/92.3%; C5:96%/85.7%; C6:85.8%/78.7%; C7:91%/80.4%. Levels of fulfilment suggest that the use of a single set of criteria for DIS in RRMS and PPMS might be feasible, and reinforce the added value of cerebrospinal fluid (CSF) findings to increase fulfilment in PPMS. Unification of the DIS criteria for both RRMS and PPMS could be considered in further revisions of the MS diagnostic criteria.

Published
2009
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20. Induction of serum soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin-1 receptor antagonist (IL-1ra) by interferon beta-1b in patients with progressive multiple sclerosis

Author

Ana Rovira, Luis Brieva, Cristina López, Xavier Montalban, N. Téllez, Eva Julià, Manuel Comabella, José Antonio del Río, and Mar Tintoré

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Statistics as Topic, Enzyme-Linked Immunosorbent Assay, Interleukin-1 receptor, Receptors, Tumor Necrosis Factor, Etanercept, Proinflammatory cytokine, Adjuvants, Immunologic, Double-Blind Method, Internal medicine, medicine, Humans, Analysis of Variance, business.industry, Multiple sclerosis, Interferon beta-1b, Interferon-beta, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Interleukin 1 Receptor Antagonist Protein, Interleukin 1 receptor antagonist, Endocrinology, Cytokine, Neurology, Immunoglobulin G, Interleukin-21 receptor, Female, Neurology (clinical), business, Blood sampling
Abstract

Cytokine inhibitors, such as soluble tumor necrosis factor receptor II (sTNFRII) and interleukin-1 receptor antagonist (IL-1ra) are possible regulators of proinflammatory cytokine activity. Although previous studies have shown induction of sTNF-RII and IL-1ra by interferon-beta (IFNbeta) in patients with relapse-onset forms of multiple sclerosis (MS), to date no studies of these cytokine inhibitors have been performed in patients with essentially progressive forms of MS.To address the effects of IFNbeta on serum levels of sTNF-RII and IL-1ra in a cohort of progressive MS patients and to assess the relationship between levels and changes of sTNF-RII and IL-1ra and clinical and radiological variables. Methods Serial blood samples were obtained from a cohort of 73 patients with progressive MS who participated in a placebo-controlled clinical trial with IFNbeta-1b. Serum levels of sTNF-RII and IL-1ra were measured by multiplex enzyme-linked immunosorbent assay at baseline and after 3, 6, 12, and 24 months. EDSS and MSFC scores were recorded at the time of blood sampling, and MR scans were obtained at baseline and after 12 and 24 months.Treatment with IFNbeta was associated with significant increases of sTNF-RII and IL-1ra serum levels during the followup period. A strong correlation at 24 months was observed between levels of sTNF-RII and EDSS scores in the placebo group. Finally, a trend for negative association was found between changes in sTNFRII and percentage change in T2-weighted lesion load at 24 months in the IFNbeta treated group.sTNF-RII and IL-1ra levels are increased in the serum of progressive MS patients during IFNbeta therapy and may be one mechanism by which IFNbeta mediates its effects in the treatment of MS.

Published
2008
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21. Relationship between MRI lesion activity and response to IFN-β in relapsing–remitting multiple sclerosis patients

Author

N. Téllez, Carlos Nos, Jordi Río, Manuel Comabella, Mar Tintoré, Ana Rovira, Carmen Tur, E. Huerga, and Xavier Montalban

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Sensitivity and Specificity, Central nervous system disease, Lesion, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Degenerative disease, Predictive Value of Tests, medicine, Humans, Immunologic Factors, Longitudinal Studies, Prospective Studies, Prospective cohort study, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, Interferon-beta, Middle Aged, Prognosis, medicine.disease, Magnetic Resonance Imaging, Surgery, Treatment Outcome, Neurology, Predictive value of tests, Regression Analysis, Female, Neurology (clinical), Radiology, medicine.symptom, business, Follow-Up Studies
Abstract

Objective Our objective in this study is to evaluate whether brain magnetic resonance imaging (MRI) performed at interferon-beta (IFN-β) onset and after 12 months allow us to identify relapsing–remitting multiple sclerosis (RRMS) patients with a disability increase in the first 2 years of therapy. Methods This is a prospective and longitudinal study of patients with RRMS treated with IFN-β. All patients included underwent brain MRI before the onset of therapy with IFN-β and 12 months after. MRI measures (T2, unenhanced T1-weighted and gadolinium-enhancing T1-weighted brain lesion load, brain parenchymal fraction) were undertaken at baseline and after 12 months. The number of active lesions (new or enlarging T2 plus gadolinium-enhancing brain lesions) was also assessed on the 12 months MRI scan. Expanded Disability Status Scale (EDSS) was scored every 3 months. We defined an increase in disability as an increase of at least 1 EDSS point confirmed and sustained during the first 2 years of therapy with IFN-β. Regression analysis was performed in order to identify MRI variables of response. Results We included 152 patients who were followed-up for at least 2 years. After 2 years of therapy, 24 patients (16%) had an increase in disability. The logistic regression model showed that active lesions in the scan performed at 12 months were the most important factor related with the increase of disability after 2 years of therapy (odds ratio 8.3, 95% confidence interval 3.1–21.9; p < 0.0001). Conclusions In RRMS patients treated with IFN-β the MRI changes occurring during the first year may have a prognostic value for identifying patients with a confirmed increase of disability after 2 years of therapy.

Published
2008
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22. The basal ganglia: a substrate for fatigue in multiple sclerosis

Author

N. Téllez, Carlos Nos, Xavier Montalban, Mar Tintoré, Alex Rovira, Juli Alonso, and José Antonio del Río

Subjects
Adult, Male, medicine.medical_specialty, Magnetic Resonance Spectroscopy, Neurology, Adolescent, Lentiform nucleus, Central nervous system, Gastroenterology, Choline, Central nervous system disease, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Reference Values, Risk Factors, Internal medicine, Basal ganglia, Image Processing, Computer-Assisted, medicine, Humans, Radiology, Nuclear Medicine and imaging, Fatigue, Neuroradiology, Aspartic Acid, Fourier Analysis, medicine.diagnostic_test, business.industry, Multiple sclerosis, Magnetic resonance imaging, Middle Aged, Creatine, medicine.disease, Magnetic Resonance Imaging, Corpus Striatum, Frontal Lobe, medicine.anatomical_structure, Endocrinology, Female, Neurology (clinical), Energy Metabolism, Cardiology and Cardiovascular Medicine, business
Abstract

The origin of fatigue in multiple sclerosis (MS) remains uncertain. However, the use of nonconventional magnetic resonance techniques has increased our understanding of this problem. We aimed to study the relationship between fatigue in MS and the presence of focal dysfunction in the basal ganglia and frontal white matter. Included in the study were 41 patients with relapsing–remitting MS with mild disability and 20 healthy controls. Fatigue was assessed by the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Patients were classified as “fatigued” when they expressed a subjective feeling of fatigue, and the FSS score was ≥5.0 and/or the MFIS score was >38. Patients with no subjective fatigue were classified as “nonfatigued” when the FSS score was

Published
2007
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23. Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis?

Author

Jaume Sastre-Garriga, N. Téllez, Carmen Tur, Alex Rovira, Manuel Comabella, Carlos Nos, Xavier Montalban, H Perkal, Mar Tintoré, Jordi Río, and Raul Pelayo

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Oligoclonal band, Severity of Illness Index, Gastroenterology, Cohort Studies, Central nervous system disease, Disability Evaluation, Predictive Value of Tests, Recurrence, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, Oligoclonal Bands, Hazard ratio, Brain, Magnetic resonance imaging, Prognosis, medicine.disease, Magnetic Resonance Imaging, Surgery, Predictive value of tests, Disease Progression, Female, Neurology (clinical), business, Biomarkers, Follow-Up Studies
Abstract

Background: To evaluate whether oligoclonal bands (OB) add information to MRI in predicting both a second attack and development of disability in patients with clinically isolated syndromes (CIS). Methods: From 1995 to 2006, 572 patients with CIS were included in a prospective study. Patients underwent brain MRI and determination of OB within 3 months of first attack. The number and location of lesions and presence of OB were studied. We analyzed time to second attack and to Expanded Disability Status Scale 3.0 according to number of Barkhof criteria (BC) and the presence or absence of OB. Results: We studied 415 (73%) patients with CIS with both baseline MRI and determination of OB. Patients were followed for a mean of 50 months (SD 31). Compared to the reference group with 0 BC at baseline MRI, patients with one to two BC showed a hazard ratio (HR) for conversion to CDMS of 3.8 (2.0 to 7.2) and patients with three to four BC of 8.9 (4.8 to 16.4). Of the total cohort, OB were positive in 61% of the patients. However, broken down by MRI group, OB were positive in 31% of those with no BC; 69% of those with one to two BC; and 85% of those with three or four BC. The presence of OB increased the risk of a second relapse (HR 1.7; 1.1 to −2.7) independently of baseline MRI but did not modify the development of disability. Conclusions: Presence of oligoclonal bands doubles the risk for having a second attack, independently of MRI, but does not seem to influence the development of disability. GLOSSARY: BC = Barkhof criteria; CDMS = clinically definite multiple sclerosis; CIS = clinically isolated syndromes; EDSS = Expanded Disability Status Scale; HR = hazard ratio; MS = multiple sclerosis; OB = oligoclonal bands.

Published
2007
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24. Nueva fuente de quinoles, la superficie foliar de Pentacalia ledifolia y Pentacalia corymbosa y sus propiedades antifúngicas

Author

Alvaro Granados, Julio A. Pedrozo, Alba N. Téllez, and Rubén Torrenegra

Subjects
Antifungal, biology, medicine.drug_class, Chemistry, Pentacalia corymbosa, lcsh:RS1-441, Senecioneae, Asteraceae, quinóides, biology.organism_classification, Pentacalia, antifungical activity, lcsh:Pharmacy and materia medica, quinols, Pentacalia ledifolia, Botany, medicine, atividade antifúngica, General Pharmacology, Toxicology and Pharmaceutics
Abstract

Foi demonstrada a ação antifúngica do extrato clorofórmico e de duas substâncias isoladas da superfície foliar de Pentacalia ledifolia (H.B.K.) Cuatr. e P. corymbosa (Benth) Cuatr. frente aos fungos fitopatógenos Fusarium oxysporum e Botrytis cinerea, cultivados em BDA (batata-dextrose-ágar). Destes extratos foram isolados, além de cumarinas já identificadas em estudos anteriores, dois derivados quinóides: (1-hidroxi-4-oxo-2,5-ciclohexadienil) acetato de metila ou jacaranona e (1-hidroxi-4-oxo-2,5-ciclohexadienil) acetato de etila ou metiljacaranona. Para o (1-hidroxi-4-oxo-2,5-ciclohexadienil) acetato de etila foi calculado CI50 de 650 μg/mL para os dois tipos de fungos e o (1-hidroxi-4-oxo-2,5-ciclohexadienil) acetato de metila teve um CI50 de 660 μg/mL. Quinols identified in the surface waxes of Pentacalia ledifolia (H.B.K.) Cuatr and P. corymbosa (Benth) Cuatr. leaves, possess antifungal activity against Fusarium oxysporum and Botrytis cinerea, cultured on PDA (potato-dextrose-agar) medium. These extracts were prepared by dipping fresh leaves in chloroform for 5 min, and afforded ethyl-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl) acetate and methyl-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl) acetate, the major surface compounds.

Published
2006
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25. Baseline MRI predicts future attacks and disability in clinically isolated syndromes

Author

N. Téllez, Mar Tintoré, Carlos Nos, E. Grivé, Raul Pelayo, Manuel Comabella, Jordi Río, Xavier Montalban, Alex Rovira, and Jaume Sastre-Garriga

Subjects
Adult, Male, Risk, medicine.medical_specialty, Multiple Sclerosis, Time Factors, Sensitivity and Specificity, Severity of Illness Index, Disability Evaluation, Predictive Value of Tests, Recurrence, Internal medicine, Severity of illness, medicine, Humans, Retrospective Studies, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, Hazard ratio, Brain, Magnetic resonance imaging, Retrospective cohort study, Syndrome, medicine.disease, Magnetic Resonance Imaging, Surgery, Predictive value of tests, Multivariate Analysis, Cohort, Female, Neurology (clinical), business
Abstract

To determine the relation between baseline MRI and both conversion to multiple sclerosis (MS) and development of disability in a cohort of patients with clinically isolated syndromes (CIS).From 1995 to 1998, 175 consecutive patients with CIS underwent brain MRI within 3 months of their first attack and again 12 months and 5 years later. We studied the number and location of lesions at baseline and development of new T2 lesions. We also analyzed conversion to MS and development of disability (Expanded Disability Status Scale [EDSS]or = 3.0).We included 156 patients with CIS followed for a median of 7 years. Compared to the reference group with 0 Barkhof criteria at baseline MRI, patients with one or two Barkhof criteria showed an adjusted hazard ratio (HR) of 6.1 (2.2 to 16.6) and patients with three to four Barkhof criteria of 17.0 (6.7 to 43) for conversion to MS and differentiated patients with low, medium, and high conversion risk. EDSS at year 5 correlated with baseline number of Barkhof criteria (r = 0.46, p0.0001). When categorizing by number of baseline lesions, similar results were seen. Patients with a baseline MRI with three to four Barkhof criteria had an adjusted HR of 3.9 (1.1 to 13.6) for reaching EDSSor = 3.0. Only 10% of the latter had disability at year 5, but 40% reached this at 8 years.Baseline MRI determines the risk for converting to clinically definite multiple sclerosis and correlates with disability at 5 years. The proportion of patients developing disability is low during the first 5 years but rapidly increases shortly after.

Published
2006
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26. Defining the response to interferon‐β in relapsing‐remitting multiple sclerosis patients

Author

Xavier Montalban, Jordi Río, Manuel Comabella, Ingrid Galán, Carlos Nos, N. Téllez, Mar Tintoré, and Raul Pelayo

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Sensitivity and Specificity, Central nervous system disease, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Interferon β, Internal medicine, medicine, Humans, Demography, Retrospective Studies, business.industry, Multiple sclerosis, Hazard ratio, Retrospective cohort study, Interferon-beta, medicine.disease, Confidence interval, Surgery, Clinical trial, Treatment Outcome, Neurology, Relapsing remitting, Disease Progression, Female, Neurology (clinical), business, Follow-Up Studies
Abstract

Objective Many patients with multiple sclerosis (MS) are currently receiving treatment with interferon (IFN)–β. Early identification of nonresponder patients is crucial to try different therapeutic approaches. We investigated various criteria of treatment response to assess which criterion better identifies patients with a poor response. Methods We studied relapsing-remitting MS (RRMS) patients treated with IFN-β and followed them up for at least 2 years. Expanded Disability Status Score was scored every 3 months and relapses were recorded. We analyzed various criteria based on relapses, disability progression, or both. Results Three hundred ninety-three patients were included. After 2 years of treatment, we observed a proportion of nonresponders, ranging from 7 to 49% depending on the stringency of the criteria used. Criteria based in disability progression had higher sensitivity, specificity, and accuracy. The hazard ratio for the development of marked disability after 6 years of treatment was 39.6 (95% confidence interval, 16.6–94.4) among the patients who fulfilled the criterion based only in disability progression. Interpretation Criteria of response to IFN-β therapy in RRMS using disability progression are more clinically relevant than those based only in relapse rate. This finding may be important for the counseling and care of RRMS patients treated with IFN-β. Ann Neurol 2006;59:344–352

Published
2006
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27. Interferon beta in relapsing–remitting multiple sclerosis

Author

N. Téllez, Mar Tintoré, Jordi Río, Carlos Nos, Xavier Montalban, and Ingrid Galán

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Internal medicine, Secondary Prevention, medicine, Humans, Adverse effect, Survival analysis, Demography, Retrospective Studies, business.industry, Drug Administration Routes, Multiple sclerosis, Interferon beta-1b, Interferon beta-1a, Retrospective cohort study, Interferon-beta, medicine.disease, Survival Analysis, Surgery, Clinical trial, Neurology, Cohort, Female, Neurology (clinical), business, Follow-Up Studies, medicine.drug
Abstract

Long-term observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data of our cohort of relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta (IFNbeta).We analysed RRMS patients followed for at least 2 years. From 1995, we initiated therapy with IFNbeta. As they became available, patients were allocated to one of the IFNs at standard doses (IFNbeta-1b, IFNbeta-1a i.m. or IFNbeta-1a s.c.). Each patient was included in a follow-up protocol containing demographic and baseline clinical data.Between 1995 and 2004, 382 patients have completed at least 2 years of follow-up. Significant differences at entry were observed. Patients on IFNbeta-1b had a higher disease activity and disability at baseline than those on IFNbeta-1a i.m. or IFNbeta-1a s.c. A significant reduction in the relapse rate was observed for the three drugs (70% for IFNbeta-1b, 64% for IFNbeta-1a i.m. and 74% for IFNbeta-1a s.c.). We observed a sustained progression of disability in 11% of patients on IFNbeta-1b, 17% on IFNbeta-1a i.m. and 19% on IFNbeta-1a s.c.; and at four years of follow-up in 24% of patients on IFNbeta-1b, 23% on IFNbeta-1a i.m. and 35% on IFNbeta-1a s.c. No unexpected major adverse events were observed with any of the drugs.Interferon beta is safe and well tolerated. The various registered interferon beta drugs provide a comparable efficacy in a large non-selected cohort of RRMS patients.

Published
2005
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28. Differential expression of AP-1 transcription factor genes c-fos and c-jun in the helminth parasites Taenia crassiceps and Taenia solium

Author

Carlos Larralde, Mauricio Rodríguez-Dorantes, G. Escobedo, Marco Cerbón, N. Téllez-Ascencio, and Jorge Morales-Montor

Subjects
Molecular Sequence Data, Homology (biology), Genes, jun, Transcription (biology), Taenia solium, parasitic diseases, Gene expression, medicine, Animals, Amino Acid Sequence, Gene, Taeniasis, Southern blot, Taenia crassiceps, Base Sequence, Estradiol, biology, Reverse Transcriptase Polymerase Chain Reaction, Genes, fos, Sequence Analysis, DNA, biology.organism_classification, Molecular biology, Transcription Factor AP-1, Blotting, Southern, medicine.drug_formulation_ingredient, Infectious Diseases, Gene Expression Regulation, Animal Science and Zoology, Parasitology, RNA, Helminth, Transcription Factor Gene, Sequence Alignment
Abstract

Homologues of c-fos and c-jun from total DNA of Taenia crassiceps and Taenia solium were cloned and sequenced. The amino acid alignment analysis revealed that c-fos DNAs from T. crassiceps and T. solium were highly homologous (96%), and both have high homology compared to several mammalian c-fos proteins (93% to mouse, 96% to rat and 86% to human). The c-jun protein alignment showed higher homology (T. crassiceps and T. solium have 98%), when compared with mouse, rat and human, being 92%, 98% and 93% respectively. RT-PCR amplification of the parasite's total RNA, showed that T. crassiceps expressed both AP-1 complex genes, while T. solium only expressed c-fos. Southern blot hybridization analysis confirmed the true origin of each amplified gene. AP-1 transcription gene expression is regulated by oestradiol in the same fashion as their mammalian counterparts only in T. crassiceps. To study if AP-1 genes are involved in a physiological function of the cyst, reproduction was studied in vitro. Oestradiol treatment stimulated reproduction in T. crassiceps but not in T. solium cysticerci. This is the first report of the detection and functionality of AP-1 transcription factor genes in any species of helminth parasite.

Published
2004
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29. Improvement of fatigue in multiple sclerosis by physical exercise is associated to modulation of systemic interferon response

Author

N. Téllez, Juan F. Arenillas, María José Neri, Raquel Almansa, Jesus F. Bermejo-Martin, Miguel Archanco, and Patricia Mulero

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Health Status, Immunology, Physical activity, Physical exercise, Exercise program, Interferon, Internal medicine, Gene expression, medicine, Immunology and Allergy, Humans, Exercise, Fatigue, Whole blood, Oligonucleotide Array Sequence Analysis, Principal Component Analysis, business.industry, Multiple sclerosis, Gene Expression Profiling, Middle Aged, medicine.disease, Treatment Outcome, Neurology, Female, Neurology (clinical), Interferons, business, medicine.drug
Abstract

Mechanisms underlying multiple sclerosis (MS) fatigue and the causes of the beneficial effect of exercise on this symptom are not clarified. Our aim was to evaluate gene expression profiles in MS patients who improved their fatigue status after an exercise program and to compare them with healthy controls (HC). Gene expression in whole blood was profiled at baseline in 7 HC and also in 7 fatigued-MS patients. Patients underwent an exercise program for 6 months, and their fatigue status and gene expression profiles were again analyzed. MS patients showed a significant activation of genes participating in the systemic interferon response in comparison with HC that disappeared at the end of the program. Our results provide a biological basis for the observed benefit of exercise in MS.

Published
2014

30. Neuromyelitis optica diagnosis in clinically isolated syndromes suggestive of multiple sclerosis

Author

José Antonio del Río, Marta Rubiera, Carlos Nos, N. Téllez, Xavier Montalban, Ana Rovira, and Mar Tintoré

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Multiple Sclerosis, Optic Neuritis, Eye disease, Cohort Studies, Diagnosis, Differential, Central nervous system disease, Recurrence, medicine, Humans, Cranial nerve disease, Single-Blind Method, In patient, Neuromielitis optica, Neuromyelitis optica, business.industry, Multiple sclerosis, Neuromyelitis Optica, Brain, Optic Nerve, Myelitis, medicine.disease, Magnetic Resonance Imaging, Dermatology, Large cohort, Spinal Cord, Female, Neurology (clinical), medicine.symptom, business, Algorithms
Abstract

The authors assessed the extent of overlap between current diagnostic criteria of neuromyelitis optica (NMO) and multiple sclerosis (MS) by applying NMO criteria to a large cohort of 320 patients with clinically isolated syndromes (CIS). Twenty-three (7.2%) patients fulfilled NMO absolute criteria at some time and 1 (0.3%) also fulfilled one major supportive criterion. Therefore, even by systematically applying NMO criteria in patients with CIS, NMO diagnosis is reached infrequently.

Published
2006
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31. Efeitos citotóxicos in vitro de extratos e frações de Bursera tomentosa (Jacq.) Triana & Planch., Burseraceae, frente a linhagens celulares tumorais humanos

Author

Camargo, Jorge E. Robles, Alfonso, Alba N. Téllez, Rojas-Rozo, Ronald A., Castro, Clemencia de, and Murcia, Tulia Riveros de

Subjects
Actividad citotóxica, Bursera tomentosa, Cytotoxic activity, Tumoral cellular lines, líneas celulares tumorales, linhagens celulares tumorais, Actividads citotóxica
Abstract

A los extractos, fracciones y subfracciones obtenidos de hojas, flores y corteza de Bursera tomentosa (Jacq.) Triana & Planch., Burseraceae, se les evalúo su actividad citotóxica preliminar frente a las líneas celulares CSC-1595 y Colo 205, siguiendo el método de fraccionamiento guiado por bioensayo de citotoxicidad MTT. Los resultados obtenidos de esta prueba muestran a la subfracción en diclorometano-metanol (9.5:0.5) obtenida de la fracción acetato de etilo del extracto en éter de petróleo de hojas, como la que presentó las sustancias bioactivas con una marcada actividad citotóxica, con porcentajes de viabilidad del 3% y 15.3% a la concentración 30 µg/mL en las líneas tumorales humanas Colo 205 y CSC-1595 respectivamente. To the extracts, fractions and subfractions obtained from leaves, flowers and bark of Bursera tomentosa (Jacq.) Triana & Planch., Burseraceae, its preliminary cytotoxic activity against to the cellular lines CSC-1595 and Colo 205 were evaluated, following the MTT method. The results showed that dichloromethane-methanol (9.5:0.5) subfraction obtained of ethyl acetate part from petroleum extract of leaves, like to display the bioactives substances with a strong cytotoxic activity, showing viability percentage of 3% and 15,3% to the concentration 30 µg/mL in human tumor cellular lines Colo 205 and CSC-1595 respectively. A atividade citotóxica de extratos frações e subfrações obtidas das folhas e cascas de Bursera tomentosa (Jacq.) Triana & Planch., Burseraceae, foram preliminarmente avaliados pelo método MTT frente a linhagens celulares tumorais CSC-1595 e Colo 205. Os resultados mostraram que a subfração diclorometano-metanol (9.5:0.5), obtidos a partir da fração acetato de etila do extrato em éter de petróleo das folhas, como sendo a que apresenta substâncias bioativas com forte atividade citotóxica, taxa de viabilidade de 3% e de 15,3% na concentração de 30 µg/mL em linhagens de células tumorais humanas Colo 205 e CSC-1595, respectivamente.

Published
2010

32. Clinical features of CIS of the brainstem/cerebellum of the kind seen in MS

Author

Joaquín Castilló, Manuel Comabella, Xavier Montalban, Mar Tintoré, Ana Rovira, Carmen Tur, Jaume Sastre-Garriga, N. Téllez, Carlos Nos, José Antonio del Río, Alejandro Horga, and H Perkal

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Neurology, Multiple Sclerosis, Risk Factors, Cerebellum, medicine, Diplopia, Humans, Prospective Studies, Neuroradiology, Retrospective Studies, Dyskinesias, Gait Disturbance, Multiple sclerosis, Retrospective cohort study, McDonald criteria, Odds ratio, medicine.disease, Prognosis, Surgery, Disease Progression, Female, Neurology (clinical), medicine.symptom, Psychology, Brain Stem, Demyelinating Diseases, Follow-Up Studies
Abstract

Recognition of multiple sclerosis (MS) attacks relies mostly on clinical assessment. However, their definition based on McDonald criteria refers mostly to timing and when dealing with clinical features is rather ambiguous: "...of the kind seen in multiple sclerosis." This is heightened in clinically isolated syndromes of the brainstem/cerebellum (CISB), where clinical manifestations can be manifold. This study aimed to describe the clinical features of patients with CISB to improve clinical recognition of patients with brainstem manifestations at the onset of their MS. To this end, we conducted a retrospective analysis of case notes of consecutively recruited patients with CISB assessed within 3 months of symptoms onset. Seventy-five patients were included. Most common brainstem-specific symptoms were: diplopia (68%), facial sensory symptoms (32%) and gait disturbance (31%). Adjusting for follow-up times, total number of symptoms and presence of other brainstem-specific symptoms, only the presence of facial sensory symptoms was predictive of (a lower risk of) conversion to clinically definite (CD) MS (Odds ratio: 0.086; p = 0.007). Neither the total number of brainstem-specific, non brainstem-specific nor the sum of both predicted conversion to CDMS. Results indicate that diplopia, facial sensory symptoms and gait disturbance occur in more than 30% of patients with CISB. Facial sensory symptoms are less associated with conversion to CDMS.

Published
2009

33. Very early scans for demonstrating dissemination in time in multiple sclerosis

Author

Alex Rovira, H Perkal, Carlos Nos, Xavier Montalban, Ingrid Galán, Mar Tintoré, N Téllez, Jordi Río, Carmen Tur, Jaume Sastre-Garriga, and Manuel Comabella

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Lesion, Central nervous system disease, Multiple Sclerosis, Relapsing-Remitting, Risk Factors, medicine, Humans, Clinical significance, Child, Clinically isolated syndrome, medicine.diagnostic_test, business.industry, Multiple sclerosis, Hazard ratio, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Confidence interval, Early Diagnosis, Neurology, Disease Progression, Female, Neurology (clinical), Radiology, medicine.symptom, business, Nuclear medicine, Demyelinating Diseases, Follow-Up Studies
Abstract

Objective To evaluate the clinical significance of the 2005 modified imaging criteria for dissemination in time in multiple sclerosis stating that detection of a new T2 lesion appearing at any time compared with a reference scan done at least 30 days after the onset of a clinically isolated syndrome implies dissemination in time. Methods We included consecutive patients younger than 50 years examined at our center within 3 months of a clinical syndrome suggestive of central nervous system demyelination of the type seen in multiple sclerosis and followed for at least 3 years. We classified patients into one of two groups, according to the timing when reference scan was performed: less than 30 days and at least 30 days after symptom onset. We analyzed the interaction in time to relapse between timing of reference scan and new T2 lesion effect. Results A total of 218 patients were included. The hazard ratio (95% confidence interval) of this interaction was 0.90 (0.31–2.62) (or 1.02 (0.27–3.91) in patients with dissemination in space). Conclusions We conclude that new T2 lesions increased relapse risk regardless of timing of the reference scan, supporting the use of scans performed at any time within 30 days of symptom onset for dissemination in time demonstration.

Published
2008

34. Pregnancy in multiple sclerosis patients treated with immunomodulators prior to or during part of the pregnancy: a descriptive study in the Spanish population

Author

V. De Las Heras, C de Andrés, Mar Tintoré, and N. Téllez

Subjects
medicine.medical_specialty, Multiple Sclerosis, Abortion, Drug Administration Schedule, Medical Records, Pregnancy, medicine, Humans, Risk factor, Retrospective Studies, Obstetrics, business.industry, Medical record, Pregnancy Outcome, Retrospective cohort study, Abortion, Induced, medicine.disease, Surgery, Discontinuation, Abortion, Spontaneous, Pregnancy Complications, Parity, Breast Feeding, Neurology, Spain, Gestation, Female, Neurology (clinical), business, Breast feeding, Immunosuppressive Agents
Abstract

Objectives To study the management of pregnancy in multiple sclerosis (MS) patients on immunomodulatory therapy (IMT) in routine clinical practice and to analyze pregnancy outcomes and the clinical course of MS around pregnancy. Methods Retrospective, multicentric study in Spain in MS patients receiving IMT before conception and followed for at least three months post-partum. Results A total of 1286 medical records were reviewed. Eighty-eight pregnancies were identified in 74 (6%) women, 66% of which were unexposed and 34% exposed pregnancies. In most cases, IMT was discontinued before conception and resumed shortly after delivery. Accidental exposure to IMT did not lead to higher rates of abortions ( P = 0.76) or malformations. The relapse rate was decreased during pregnancy (0.31 versus 0.61 in the pre-pregnancy year) and increased after delivery (0.87 on month 3), returning to pre-conception values on month 12. The median EDSS score was not increased during the study. Conclusions Discontinuation of IMT before conception, and resumption shortly after delivery was the most frequent clinical practice procedure. Accidental exposure to IMT did not affect pregnancy outcomes or increased malformation rates. Pregnancy was associated with a reduced relapse rate. No factor was found to predict the risk of relapses during or after pregnancy. Multiple Sclerosis 2007; 13: 981—984. http://msj.sagepub.com

Published
2007

35. Polyregional and hemispheric syndromes: a study of these uncommon first attacks in a CIS cohort

Author

Manuel Comabella, Mar Tintoré, Xavier Montalban, Ana Rovira, N. Téllez, José Antonio del Río, Carlos Nos, Raul Pelayo, and E. Grivé

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Central nervous system, Functional Laterality, Central nervous system disease, Cohort Studies, Multiple Sclerosis, Relapsing-Remitting, medicine, Cranial nerve disease, Humans, Optic neuritis, Longitudinal Studies, Age of Onset, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, Syndrome, medicine.disease, Spinal cord, medicine.anatomical_structure, Neurology, Optic nerve, Female, Neurology (clinical), medicine.symptom, business
Abstract

Clinically isolated syndromes (CIS) classically refer to optic neuritis (ON), brainstem or spinal cord syndromes. Less common first episodes suggestive of central nervous system (CNS) demyelination, such as hemispheric or clinically polyregional syndromes, have been only slightly studied. The aim of this study was to describe these CIS topographies in our cohort of patient with a CIS. We evaluated 320 patients with a CIS, and classified the topographies of the attacks according to clinical symptoms only into CIS of the optic nerve (123), brainstem (78), spinal cord (89), hemispheric (6), polyregional (12) or undetermined (12) topographies. Patients underwent brain MRI within three months of their first attack, and again 12 months later. Conversion to multiple sclerosis (MS), determined either clinically or by magnetic resonance imaging (MRI), was evaluated according to topography. Hemispheric and polyregional syndromes were closer to brainstem or spinal cord syndromes than ON in clinical and MRI conversion terms, although a statistical analysis was not performed because of the small number of patients. There are differences between several studies in the definition, and, therefore, the prevalence of these so-called atypical CIS. Consensus on the denomination and definition of these syndromes must be reached. Multiple Sclerosis 2007; 13: 731-736. http://msj.sagepub.com

Published
2007

36. Long-term emotional state of multiple sclerosis patients treated with interferon beta

Author

José Antonio del Río, Xavier Montalban, N. Téllez, A Sánchez-Betancourt, Mar Tintoré, C. Borràs, María Jesús Arévalo, Carlos Nos, and J. Porcel

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Emotions, Logistic regression, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Adjuvants, Immunologic, Rating scale, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Humans, Psychological testing, 030212 general & internal medicine, Psychiatry, Depression (differential diagnoses), Psychiatric Status Rating Scales, Depressive Disorder, Multiple sclerosis, Beck Depression Inventory, Interferon-beta, Middle Aged, medicine.disease, Neurology, Predictive value of tests, Anxiety, Female, Neurology (clinical), medicine.symptom, Psychology, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Objective: To assess the long-term emotional state of multiple sclerosis (MS) patients treated with interferon beta (IFNβ) for at least four years. Methods: Patients who had started IFNβ therapy prior to 2000 with a baseline psychological assessment were identified and scheduled for long-term emotional assessment with the following questionnaires-the Hamilton Depression Rating Scale, the Beck Depression Inventory and the State-Trait Anxiety Inventory. Results: A total of 262 patients started IFNβ therapy in our MS clinic within the period 1995-1999. Baseline emotional assessment was available from 246 MS patients. Long-term assessment was conducted on 234 patients. After a mean follow-up of 65 months (43-98), 52 patients (22.3%) had withdrawn from IFNβ therapy. The comparisons, obtained from baseline and follow-up scores, showed an improvement in the depressive and anxiety symptoms of patients who adhered to IFNβ treatment. Logistic regression analysis indicated that an increase in physical disability and the presence of depressive symptoms at baseline were best predictors for long-term depressive symptoms. Conclusions: The present results support the absence of emotional worsening in MS patients treated with IFNβ for a long period of time. Increased disability and the presence of baseline depressive symptoms predicted the presence of depressive symptoms at follow-up.

Published
2007

37. Princípio ativo citotóxico de Espeletia killipii Cuatr. sobre células tumorais e sua toxicidade frente a células normais humanas

Author

Fabio Ancizar Aristizaba, Rubén Torrenegra, Alba N. Téllez Alfonso, Clemencia de Castro, Gustavo Jaimes, and Tulia Riveros de Murcia

Subjects
atividade citotóxica, biology, Chemistry, Myeloid leukemia, lcsh:RS1-441, biology.organism_classification, medicine.disease, Molecular biology, Epithelium, Lymphoma, lcsh:Pharmacy and materia medica, Espeletia, sesquiterpenolactona, medicine.anatomical_structure, Cell culture, Espeletia killipii, medicine, sesquiterpenelactone, Bone marrow, Viability assay, General Pharmacology, Toxicology and Pharmaceutics, K562 cells, cytotoxic activity
Abstract

De Espeletia killipi Cuart. foi isolado uma sesquiterpenlactona identificada como acetato de longipilina que mostrou atividade citotóxica. A citotoxidade foi avaliada em células normais obtidas de sangue periférico, tiróide, testículo e epitélio da boca. Células da medula óssea de pacientes com leucemia crônica mielóide, linfoma de Hodking (do Instituto Nacional de Câncer de Bogotá, Colômbia) e células K562 também foram avaliadas. A citotoxidade foi determinada através do teste MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl Tetrazolium Bromid). Os ensaios mostraram que a substância não é tóxica para células normais mas a 3 mg/mL apresentou significante atividade em células tumorais e linhagem K562. Conseqüentemente, lavando-se em conta essa significante ação, novas investigações podem ser consideradas plausíveis. The compound responsible for the citotoxic effect was identified as longipilin acetate, a sesquiterpenelactone isolated from Espeletia killipi Cuatr. Citotoxicity was assessed by using normal cells obtained from peripheral blood, thyroid, testicle and mouth epithelium. Bone marrow cells from patients with chronic myeloid leukemia, Hodking lymphoma (from Cancer National Institute, Bogotá Colombia) and the cell line K562 were also assayed. Citotoxicity was determined by the MTT cell viability test (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl Tetrazolium Bromid]. The assays revealed that the substance is risk-free on normal cells but at 3 mg/mL has significant activity on tumor cells and K562 cell line. Consequently, taken into account this significant action, new research approaches can be foreseen.

Published
2006

38. Efectos citotoxicos in vitro de extractos y fracciones de Espeletia killipii Cuatr. frente a lineas celulares tumorales humanos

Author

Alba N. Téllez Alfonso, Clemencia de Castro, Tulia Riveros de Murcia, and Rubén Torrenegra

Subjects
Espeletia killipii, atividade citotóxica, Chemistry, Active principle, lcsh:RS1-441, Asteraceae, Molecular biology, lcsh:Pharmacy and materia medica, Human tumor, Ethanol extracts, Cell culture, Immunology, Cytotoxic T cell, General Pharmacology, Toxicology and Pharmaceutics, cytotoxic activity
Abstract

O extrato etanólico e as frações de Espeletia killipii (espécie endêmica da vegetação dos páramos do altiplano Cundiboyacense); mostraram atividade citotóxica significativa in vitro nas linhagens celulares tumorais humanas de câncer de mama MCF-7, CSC-1170, CSC-1595, CSC-3322, CSC-3325 e na linhagem Hep-2 de laringe. A fração CH2Cl2 e suas sub-frações foram ativas contra as linhagens celulares cancerígenas de mama na concentração de 50 µg/mL, obtendo-se percentagens de viabilidade entre 13 e 20%. O principio ativo ainda não identificado foi obtido por ensaios bioguiados sucessivos e apresentou valores de Concentração Citotóxica media (CC50) menores que 1 µg/mL para as linhagens celulares colombianas CSC-1170, CSC-1595, CSC-3322 e CSC-3325; CC50 = 1 µg/mL contra MDA MB 435 e NCl-H23; contra MCF-7 uma CC50 = 2 µg/mL e uma CC50 superior a 16 µg/mL contra PC-3 e U-251. It was found that the ethanol extracts and fractions of Espeletia killipii (an endemic species of the páramo vegetation of the Cundiboyacense plateau) exhibited cytotoxic activity against several human tumor cell lines. Thus, the extracts and fractions exhibited significant cytotoxic activity against both the human tumor cell lines of breast cancer MCF-7, CSC-1170, CSC-1595, CSC-3322, CSC-3325 and the Hep-2 cell lines of laryns. The CH2Cl2 fraction and its sub-fractions were active against the breast lines at concentration of 50 µg/mL, with a viability percentage between 13 and 20%. The active principle, not identified yet, was obtained by successive bio-directed assays. It showed activity against the Colombian cell lines CSC-1170, CSC-1595, CSC-3322 and CSC-3325 at a half Cytotoxic Concentration (CC50) less than 1 µg/mL, against MDA MB-435 and NCI-H23 at CC50= 1 µg/mL against MCF-7 at CC50= 2 µg/mL, and against PC-3 and U-251 at CC50 greater than 16 µg/mL.

Published
2006

39. Fatigue in multiple sclerosis persists over time: a longitudinal study

Author

Ingrid Galán, Mar Tintoré, N. Téllez, Xavier Montalban, José Antonio del Río, and Carlos Nos

Subjects
Adult, Male, medicine.medical_specialty, Longitudinal study, Neurology, Multiple Sclerosis, Time Factors, Central nervous system disease, Disability Evaluation, medicine, Humans, Longitudinal Studies, Depression (differential diagnoses), Fatigue, Psychiatric Status Rating Scales, Expanded Disability Status Scale, Depression, Multiple sclerosis, Beck Depression Inventory, medicine.disease, Mood, Physical therapy, Female, Neurology (clinical), Psychology
Abstract

Fatigue is one of the most frequent symptoms in multiple sclerosis (MS) but there is a lack of knowledge about its behaviour over time. The aim of our study was to investigate changes in fatigue in a large cohort of MS patients and to determine the relationship between changes in disability and depression with changes in fatigue severity. We studied fatigue in 227 MS consecutive patients and again after one year. During the clinical interview, we recorded the patient’s degree of disability using the Expanded Disability Status Scale and relapses; fatigue was measured by means of the Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) and depression was measured by the Beck Depression Inventory (BDI). After a mean follow-up of 18 months, 86.8% of patients who were fatigued at study onset remained in a fatigued status, whereas 25% of those without fatigue at onset had become fatigued at the end of follow-up. We observed that only variations on BDI scores positively correlate with variations on fatigue scales, mainly with MFIS (r = 0.49, p

Published
2005

40. Long-term clinical outcome of primary progressive MS:Predictive value of clinical and MRI data

Author

Ana Rovira, Jaume Sastre-Garriga, Frederik Barkhof, Alan J. Thompson, Massimo Filippi, Bas Jasperse, Xavier Montalban, N. F. Kalkers, Bruno Brochet, GT Ingle, S M Leary, Valerie L. Stevenson, N. Téllez, DH Miller, Daniel R. Altmann, Vincent Dousset, Marco Rovaris, Mara Cercignani, Chris H. Polman, B. Benedetti, Radiology and nuclear medicine, Neurology, VU University medical center, Sastre Garriga, J, Ingle, Gt, Rovaris, M, Tellez, N, Jasperse, B, Altmann, Dr, Benedetti, B, Stevenson, Vl, Cercignani, M, Leary, Sm, Barkhof, F, Brochet, B, Dousset, V, Filippi, Massimo, Montalban, X, Kalkers, Nf, Polman, Ch, Rovira, A, Miller, Dh, and Thompson, Aj

Subjects
Central Nervous System, medicine.medical_specialty, Cord, Time Factors, Outcome (game theory), Nerve Fibers, Myelinated, Primary progressive, Lesion load, Cohort Studies, Disability Evaluation, Predictive Value of Tests, medicine, Humans, Longitudinal Studies, Prospective Studies, Neurologic Examination, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Data Collection, Brain, Multiple Sclerosis, Chronic Progressive, medicine.disease, Prognosis, Predictive value, Magnetic Resonance Imaging, Diffusion Magnetic Resonance Imaging, Spinal Cord, Brain size, Physical therapy, Disease Progression, Neurology (clinical), Radiology, Atrophy, business
Abstract

The authors sought to identify clinical and MRI predictors of outcome in primary progressive multiple sclerosis (PPMS). Clinical and MRI assessments were performed at baseline and 2 and 5 years (clinical only). At baseline, disease duration, expanded disability status scale (EDSS) and brain volume predicted outcome. Adding short-term change variables, baseline EDSS, changes in T2* lesion load and cord area, and number of new lesions were predictive. Clinical and MRI variables predict long-term outcome in PPMS. Copyright © 2005 by AAN Enterprises, Inc.

Published
2005
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41. Factors related with treatment adherence to interferon beta and glatiramer acetate therapy in multiple sclerosis

Author

Carlos Nos, N. Téllez, M ar Tintoré, Joana Porcel, Angela Sánchez-Betancourt, Jordi Río, Xavier Montalban, and M Jesús Arévalo

Subjects
medicine.medical_specialty, Treatment adherence, Central nervous system disease, Cohort Studies, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Internal medicine, medicine, Humans, 030212 general & internal medicine, Glatiramer acetate, business.industry, Multiple sclerosis, Glatiramer Acetate, Interferon-beta, Multiple Sclerosis, Chronic Progressive, medicine.disease, Discontinuation, Patient management, Clinical trial, Interferon-B, Neurology, Physical therapy, Patient Compliance, Drug Therapy, Combination, Neurology (clinical), business, Peptides, 030217 neurology & neurosurgery, medicine.drug, Follow-Up Studies
Abstract

Background: Awareness of the factors influencing discontinuation of immunomodulatory drugs (IMD) treatment in multiple sclerosis (MS) can help to find approaches to patient management with the aim of establishing more specific indications and also attaining more optimal patient selection in future clinical trials. Objective: To identify the causes that influence adhesion to IMD therapy within the clinical practice in a large cohort of patients with MS. Patients and methods: We have studied all MS patients who have initiated IMD in our hospital. All patients took part in training sessions where treatment expectations and side effects were explained and they received training in the administration technique. Reasons for stopping therapy were recorded during follow-up. Results: We studied 632 MS patients (mean follow-up was 47.1 (28.7) months). At the time of analysis, 107/632 patients (17%) were no longer receiving IMD. Almost half of the patients who stopped IMD (52/107) did so within the first two years on therapy. Fifty-six patients stopped IMD because of lack of efficacy. Only 27 patients (4.3%) discontinued treatment for reasons other than inefficacy or side effects. The proportion of patients with secondary progressive MS that stopped IMD therapy was 30%, while only 13.5% of the patients with relapsing—remitting MS stopped therapy (P= 0.0001). Expanded Disability Status Scale (EDSS) score at entry was the main factor that predicted interruption of therapy. Conclusions: The proportion of patients interrupting IMD in our centre is low, possibly due to individualized care. Higher EDSS, mainly in the first two years of treatment, is the main factor related with interruption. Close follow-up of these patients would be useful in avoiding early discontinuation of therapy.

Published
2005

42. Multiple sclerosis severity score: Using disability and disease duration to rate disease severity

Author

Maria José Sá, Justin P. Rubio, Bianca Miterski, S. R. Seaman, Jörg T. Epplen, Iuliana Achiti, Monica Marta, M. Coustans, Sandra Vukusic, G V McDonnell, Annette Bang Oturai, Richard Roxburgh, Maria Edite Rio, Pablo Villoslada, Bénédicte Dubois, Fabiana Tesser, Maurizio Leone, Christian Confavreux, T Masterman, Marcin P. Mycko, Gilles Edan, N. Téllez Lara, Ana Martins da Silva, Alexandra Weber, Stephen Sawcer, E. Le Page, Giuseppe Salemi, Giovanni Savettieri, P. Soelberg Sørensen, Anke Hensiek, Xavier Montalban, D. A. S. Compston, Maria Giovanna Marrosu, Helmut Butzkueven, Krzysztof Selmaj, Frauke Zipp, Maria Liguori, Isabel Leite, Stanley Hawkins, Elisabeth Gulowsen Celius, Jan Hillert, Maria Trojano, Trevor J. Kilpatrick, Eleonora Cocco, Chemical Biology 2, ROXBURGH RHSR, SEAMAN SR, MASTERMAN T, HENSIEK AE, SAWCER SJ, VUKUSIC S, ACHITI I, CONFAVREUX C, COUSTANS M, LE PAGE E, EDAN G, MCDONNELL GV, HAWKINS S, TROJANO M, LIGUORI M, COCCO E, MARROSU MG, TESSERE F, LEONE MA, WEBER A, ZIPP F, MITERSKI B, EPPLEN JT, OTURAI A, SOELBERG-SORENSEN P, CELIUS EG, TELLEZ LARA N, MONTALBAN X, VILLOSLADA P, SILVA AM, MARTA M, LEITE I, DUBOIS B, RUBIO J, BUTZKUEVEN H, KILPATRICK T, MYCKO MP, SELMAJ KW, RIO ME, SA M, SALEMI G, SAVETTIERI G, HILLERT J, and COMPSTON DAS

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, Cross-sectional study, Models, Neurological, Disease, SUSCEPTIBILITY, Severity of Illness Index, Cohort Studies, Disability Evaluation, Predictive Value of Tests, Recurrence, Severity of illness, medicine, Humans, Longitudinal Studies, Age of Onset, Models, Statistical, Expanded Disability Status Scale, business.industry, Multiple sclerosis, OUTCOME MEASURE, Reproducibility of Results, NATURAL-HISTORY, Middle Aged, Prognosis, medicine.disease, Cross-Sectional Studies, Predictive value of tests, Disease Progression, Physical therapy, Female, France, Neurology (clinical), Age of onset, business, Cohort study
Abstract

Background: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. Methods: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. Results: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. Conclusion: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Published
2005

43. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author

S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. 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Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, L, Villela, N, Laflor, C, Conde, C, Bottino, D, Dorigo, D, Bouskela, E, Pu, S, Luo, Z, Lam, K, Dan, Q, Xu, A, Shen, J, Cheng, K, Xu, J, Thamer, C, Stefan, N, Haap, M, Heller, E, Tschritter, O, De Prado, A, Ortiz, A, Ybarra, J, Gich, I, Pou, J, Ehren, M, Roggenland, D, Reinsen, B, Klein, H, Rittig, K, Stock, J, Kocher, B, Balletshofer, B, Shon, H, Chung, D, Nakatani, Y, Matsuhisa, M, Kaneto, H, Hatazaki, M, Yoshiuchi, K, Katakami, N, Kawamori, D, Ohtoshi, K, Sakamoto, K, Matsuoka, T, Ozawa, K, Ogawa, S, Hori, M, Yamasaki, Y, Zitouni, K, Harry, D, Nourooz zadeh, J, Earle, K, Olesen, P, Franco, L, Corvaja, C, Semplicini, A, Ceylan işık, A, Arı, N, Rösen, P, Lee, I, Park, K, Jung, E, Shin, D, Jo, S, Obuobie, K, Prakash, P, Hanna, F, Lazarus, J, Varadhan, L, Gurushankar, J, James, D, Sheikh, S, Gaede, P, Zou, D, Vilarrasa, N, Perez maraver, M, Mena, E, Perez, D, Setti, G, Buckingham, R, Urbančič, V, Stefanovska, A, Bernjak, A, Ažman juvan, K, Kocijančič, A, Glowania, A, Filters, T, Fosmark, D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H

Subjects
0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published
2004

44. Evidence that steroid 5alpha-reductase isozyme genes are differentially methylated in human lymphocytes

Author

M. Lizano-Soberón, Ignacio Camacho-Arroyo, Mauricio Rodríguez-Dorantes, Sumiko Morimoto, R. Calzada-León, N. Téllez-Ascencio, and Marco Cerbón

Subjects
Male, HpaII, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Biology, Biochemistry, Isozyme, Polymerase Chain Reaction, Exon, Endocrinology, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Humans, Lymphocytes, Molecular Biology, Gene, DNA Primers, Genetics, Base Sequence, Point mutation, Cell Biology, Methylation, DNA Methylation, Molecular biology, Isoenzymes, Differentially methylated regions, Case-Control Studies, DNA methylation, Molecular Medicine
Abstract

The synthesis of dihydrotestosterone (DHT) is catalyzed by steroid 5alpha-reductase isozymes 1 and 2, and this function determines the development of the male phenotype during embriogenesis and the growth of androgen sensitive tissues during puberty. The aim of this study was to determine the cytosine methylation status of 5alpha-reductase isozymes types 1 and 2 genes in normal and in 5alpha-reductase deficient men. Genomic DNA was obtained from lymphocytes of both normal subjects and patients with primary 5alpha-reductase deficiency due to point mutations in 5alpha-reductase 2 gene. Southern blot analysis of 5alpha-reductase types 1 and 2 genes from DNA samples digested with HpaII presented a different cytosine methylation pattern compared to that observed with its isoschizomer MspI, indicating that both genes are methylated in CCGG sequences. The analysis of 5alpha-reductase 1 gene from DNA samples digested with Sau3AI and its isoschizomer MboI which recognize methylation in GATC sequences showed an identical methylation pattern. In contrast, 5alpha-reductase 2 gene digested with Sau3AI presented a different methylation pattern to that of the samples digested with MboI, indicating that steroid 5alpha-reductase 2 gene possess methylated cytosines in GATC sequences. Analysis of exon 4 of 5alpha-reductase 2 gene after metabisulfite PCR showed that normal and deficient subjects present a different methylation pattern, being more methylated in patients with 5alpha-reductase 2 mutated gene. The overall results suggest that 5alpha-reductase genes 1 and 2 are differentially methylated in lymphocytes from normal and 5alpha-reductase deficient patients. Moreover, the extensive cytosine methylation pattern observed in exon 4 of 5alpha-reductase 2 gene in deficient patients, points out to an increased rate of mutations in this gene.

Published
2002

45. [Posterior spinal artery infarction and nonbacterial thrombotic endocarditis]

Author

N, Téllez Lara, J, Montaner, J, Río, J, Alvarez Sabin, A, Ortega, and A, Codina

Abstract

Nonbacterial thrombotic endocarditis (NBTE) has been described as an important complication in patients affected by different kind of illnesses, above all underlying malignancies. Fifty % of the patients affected by NBTE will have embolic events in different organs. The poverty of specific symptomatology appears to difficult seriously its diagnosis. In fact, systemic embolic infarctions are usually asymptomatic, except when central nervous system is involved. We present a patient affected by NBTE with an asymptomatic cervical spinal cord infarction, which diagnosis was made by pathologic study. The difficulty to explore typical sings of spinal lesion and the absence of previous reported cases of NBTE with posterior spinal artery infarction, make this one fairly interesting. We think that fibrinoplatelet embolism from NBTE should be included in the etiology of the posterior spinal artery infarction.

Published
2002

46. Efecto a largo plazo de los anticuerpos neutralizantes de interferón beta-1 b en pacientes con esclerosis múltiple

Author

Ingrid Galán, Mar Tintoré, Xavier Montalban, Jordi Río, N. Téllez, and Carlos Nos

Subjects
business.industry, Medicine, General Medicine, business, Humanities
Abstract

Fundamento y objetivo Evaluar la relacion entre la presencia de anticuerpos neutralizantes (AN) de interferon beta-1 b (IFN-s-1 b) en pacientes con esclerosis multiple (EM) y su evolucion clinica en los anos siguientes. Pacientes y metodo Tal y como se ha descrito previamente, determinamos la presencia de AN en 68 pacientes con EM tratados con IFN-s-1 b a los 2 anos de tratamiento. Prospectivamente, hemos seguido esta cohorte durante un periodo minimo de 6 anos y se han recogido datos sobre los brotes, la discapacidad, los efectos secundarios y los abandonos de la medicacion. Resultados Durante el periodo de observacion de 6 anos, la tasa anual de brotes no fue diferente en los pacientes con y sin AN. Se observo una progresion confirmada de la discapacidad en el 38% de los pacientes con AN y en el 33% de los que no tenian AN. Tampoco se hallaron diferencias en la proporcion de pacientes que alcanzaron una puntuacion en la escala de discapacidad de Kurtzke (EDSS) de 6. Los efectos secundarios fueron similares en ambos grupos. Conclusiones Nuestros resultados no apoyan el efecto negativo de la presencia de AN en la evolucion clinica de los pacientes con EM tratados con IFN-s-1 b.

Published
2005
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49. Interferon Beta-1b for the Treatment of Primary Progressive Multiple Sclerosis

Author

N. Téllez, Mar Tintoré, Ingrid Galán, Xavier Montalban, F. X. Aymerich, Alex Rovira, Luis Brieva, Carmen Tur, H Perkal, Carlos Nos, Jordi Río, David Calle, Jaume Sastre-Garriga, and Manuel Comabella

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Neuropsychological Tests, Placebo, Atrophy, Double-Blind Method, Arts and Humanities (miscellaneous), Internal medicine, medicine, Humans, Aged, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, Interferon beta-1b, Magnetic resonance imaging, Interferon-beta, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Clinical trial, Treatment Outcome, Multiple sclerosis functional composite, Physical therapy, Female, Neurology (clinical), business, Follow-Up Studies
Abstract

To investigate, during the 5-year period without treatment after termination of a 2-year clinical trial of interferon beta-1b for the treatment of primary progressive multiple sclerosis, differences in the evolution of clinical variables and magnetic resonance imaging results between trial arms and to investigate correlations between in-trial changes in Multiple Sclerosis Functional Composite (MSFC) score and magnetic resonance imaging variables and Expanded Disability Status Scale (EDSS) score evolution.Five-year clinical trial follow-up.Clinical Neuroimmunology Unit, Multiple Sclerosis Centre of Catalonia, Autonomous University of Barcelona, Spain. Patients Seventy-three patients received interferon beta-1b or placebo during the trial.After 5 years without treatment, the EDSS and MSFC measures were scored for 63 and 59 patients, respectively. Neuropsychological and magnetic resonance imaging assessments were performed for 59 and 50 patients, respectively.After 5 years without treatment, the interferon beta-1b group had better 9-Hole Peg Test (P = .02) and Word List Generation Test (P .001) scores, and their magnetization transfer ratio measures in the normal-appearing white matter were significantly higher (P = .02, P = .009, and P = .03 for the mean, peak location, and peak height magnetic transfer ratios, respectively). During the entire study period (from trial baseline to assessment at 5 years without treatment), the placebo group showed a greater decrease in brain parenchymal fraction (P = .004). The in-trial increase of lesions correlated with the worsening of the EDSS score during the 5-year period without treatment (P = .004).Modest but beneficial effects of interferon beta-1b on clinical variables and brain atrophy development were observed 5 years after trial termination. Moreover, in-trial lesion activity correlated with EDSS progression after trial termination. Therefore, we provide evidence to consider immunomodulation as a sensible approach to treat primary progressive multiple sclerosis.

Published
2011
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50. Revisión de las novedades presentadas en el XXVI Congreso del Comité Europeo para el Tratamiento e Investigación en Esclerosis Múltiple (ECTRIMS) (I)

Author

E. Matas, Manuel Comabella, M C Calles-Hernandez, Lluís Ramió-Torrentà, Celia Oreja-Guevara, Luis Brieva, L M Villar, Alfredo Rodríguez-Antigüedad, Oscar Fernandez, J.A. García-Merino, Guillermo Izquierdo, M M Mendibe-Bilbao, Ana Saiz, J.M. Prieto, B Casanova-Estruch, Munoz-Garcia D, V.L. de las Heras, Rafael Arroyo-Gonzalez, Javier Olascoaga, C Arnal-Garcia, M. Tintoré, Hernández-Pérez, N. Téllez, and José Meca-Lallana

Subjects
Oncology, medicine.medical_specialty, business.industry, General Medicine, Clinical trial, chemistry.chemical_compound, Natalizumab, Daclizumab, chemistry, Ponesimod, Internal medicine, Teriflunomide, medicine, Secukinumab, Neurology (clinical), Glatiramer acetate, business, Laquinimod, medicine.drug
Abstract

The most significant data presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in France in October 2012, have been summarised in the fifth edition of the Post-ECTRIMS Experts Meeting, held in Madrid in October 2012. This led to the drafting of this review, which has been published in three parts. This third part of the Post-ECTRIMS review presents the findings from the latest studies conducted with disease-modifying treatments, more specifically with glatiramer acetate, laquinimod, ponesimod, BG-12, teriflunomide, daclizumab, natalizumab and secukinumab (AIN457). Likewise, we also address the reasons that justify the search for innovative treatments for multiple sclerosis, with antigen-specific therapy, cell therapy and therapy aimed at promoting remyelination being highlighted among other future therapeutic strategies. Access to new pharmacological agents and the complexity of the therapy of multiple sclerosis in the future will require new design strategies and directions in clinical trials, including the use of surrogate markers, new statistical applications, superiority, inferiority or equivalence clinical trials and adaptable designs. © 2013 Revista de Neurologia.

Published
2011
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