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1. Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET

Author

Kaiser, Lena, Quach, S., Zounek, A. J., Wiestler, B., Zatcepin, A., Holzgreve, A., Bollenbacher, A., Bartos, L. M., Ruf, V. C., Böning, G., Thon, N., Herms, J., Riemenschneider, M. J., Stöcklein, S., Brendel, M., Rupprecht, R., Tonn, J. C., Bartenstein, P., von Baumgarten, L., Ziegler, S., and Albert, N. L.

Published
2024
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4. Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET.

Author

Kaiser, Lena, Quach, S., Zounek, A. J., Wiestler, B., Zatcepin, A., Holzgreve, A., Bollenbacher, A., Bartos, L. M., Ruf, V. C., Böning, G., Thon, N., Herms, J., Riemenschneider, M. J., Stöcklein, S., Brendel, M., Rupprecht, R., Tonn, J. C., Bartenstein, P., von Baumgarten, L., and Ziegler, S.

Subjects
POSITRON emission tomography, RADIOMICS, CENTRAL nervous system tumors, RECEIVER operating characteristic curves, MAGNETIC resonance imaging, FEATURE extraction
Abstract

Purpose: According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively. Methods: Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied. Results: TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97). Conclusion: The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Multimodale Radiomicsanalysen zur Prädiktion des IDH-Mutationsstatus bei erstdiagnostizierten Gliomen

Author

Kaiser, L., additional, Quach, S., additional, Zounek, A. J., additional, Zatcepin, A., additional, Holzgreve, A., additional, Bollenbacher, A., additional, Bartos, L., additional, Ruf, V., additional, Böning, G., additional, von Baumgarten, L., additional, Thon, N., additional, Herms, J., additional, Riemenschneider, M. J., additional, Stöcklein, S., additional, Brendel, M., additional, Rupprecht, R., additional, Tonn, J. C., additional, Bartenstein, P., additional, Ziegler, S., additional, and Albert, N. L., additional

Published
2023
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7. Tumoral translocator protein expression is associated with microglia-related whole brain inflammation in glioblastoma

Author

Bartos, L., additional, Quach, S., additional, Kirchleitner, S. V., additional, Blobner, J., additional, Kunte, S. T., additional, Beumers, P., additional, Hörmann, L., additional, Wind-Mark, K., additional, Holzgreve, A., additional, Bartenstein, P., additional, Tonn, J. C., additional, von Baumgarten, L., additional, Brendel, M., additional, and Albert, N. L., additional

Published
2023
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8. Specificity of 18_kDa translocator protein tracer retention in single cells and non-cellular compartments of experimental glioblastoma

Author

Hörmann, L., additional, Kirchleitner, S. V., additional, Blobner, J., additional, Wind-Mark, K., additional, Holzgreve, A., additional, Quach, S., additional, Englert, A., additional, Hummel, S., additional, Lindner, S., additional, Joseph, E., additional, Bartenstein, P., additional, Tonn, J. C., additional, von Baumgarten, L., additional, Albert, N. L., additional, Brendel, M., additional, and Bartos, L. M., additional

Published
2023
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9. Specific NPC1 loss in microglia of the mouse brain leads to neuroinflammation and results in synaptic loss

Author

Hummel, S., additional, Dinkel, L., additional, Bartos, L. M., additional, Wind-Mark, K., additional, Slemann, L., additional, Kunze, L., additional, Englert, A., additional, Hörmann, L., additional, Gnörich, J., additional, Lindner, S., additional, Bartenstein, P., additional, Albert, N. L., additional, Brendel, M., additional, and Tahirovic, S., additional

Published
2023
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10. Depletion and activation of microglia alter metabolic connectivity of the mouse brain

Author

Gnörich, J., additional, Reifschneider, A., additional, Wind, K., additional, Zatcepin, A., additional, Kunte, S., additional, Beumers, P., additional, Bartos, L., additional, Wiedemann, T., additional, Grosch, M., additional, Xiang, X., additional, Khojasteh-Fard, M., additional, Ruch, F., additional, Werner, G., additional, Koehler, M., additional, Slemann, L., additional, Hummel, S., additional, Haass, C., additional, Capell, A., additional, Ziegler, S., additional, and Brendel, M., additional

Published
2023
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11. Microglia drive TSPO PET signal increases in a tauopathy mouse model

Author

Englert, A. L., additional, Bartos, L. M., additional, Palleis, C., additional, Hummel, S., additional, Hörmann, L., additional, Schlaphoff, L., additional, Kunze, L. H., additional, Gnörich, J., additional, Wind-Mark, K., additional, Lindner, S., additional, Bartenstein, P., additional, Simons, M., additional, Ziegler, S., additional, Albert, N. L., additional, Levin, J., additional, and Brendel, M., additional

Published
2023
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13. Perceived Benefits of a Remote Yoga and Mindfulness Program for Student Musicians During COVID-19.

Author

Bartos, L. Javier, Posadas, M. Pilar, and Krägeloh, Chris

Subjects
*COVID-19 pandemic, *PERCEIVED benefit, *POSITIVE psychology, *MINDFULNESS, *EMOTION regulation, *EMOTIONAL intelligence, *YOGA
Abstract

This qualitative study was conducted with participants from a previous investigation that explored the applicability and perceived impact of a program based on yoga, mindfulness, emotional intelligence, and positive psychology, to enhance student musicians' health and well-being during the lockdown. This program is named CRAFT, the acronym of which stands for the following Spanish terms that constitute its 5 elements: Consciencia, Relajación, Atención, Felicidad, and Transcendencia. The current study aimed to gain a greater understanding of participants' CRAFT-based practice implementation experience and their perceived benefits derived from it during the lockdown. Participants were higher education student musicians (n = 26) attending CRAFT-based elective subjects of Mindfulness and Emotional Intelligence, once a week for 1 hr throughout the academic year 2019/2020; at a Royal Conservatory of Music in Spain. Participants' responses to an open-ended question were content analyzed following a deductive approach guided by the framework of the 5 CRAFT elements. The content analysis revealed 6 overarching themes, 1 for each CRAFT element and an additional 1 labeled "other." Participants' perceived benefits aligned with the 5 CRAFT elements and included developments such as enhanced conscious awareness, emotional self-regulation, psychological distress, mind clearance, relaxation, concentration, wellness, vitality, hope, transforming attitudes, equanimity, positivity, and resilience. These findings suggest that curricular exposure with the CRAFT program was beneficial among higher education student musicians to cope with their health and well-being lockdown demands, having thus relevant implications in both higher education and clinical settings for health and well-being promotion, support, and prevention during stressful pandemic times. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Suckling behavior in captive plains zebra (Equus burchellii): sex differences in foal behavior

Author

Pluhacek, J., Bartosova, J., and Bartos, L.

Subjects
Zebras -- Behavior, Parental behavior in animals -- Comparative analysis, Sucking behavior -- Comparative analysis, Thumb sucking -- Comparative analysis, Zoology and wildlife conservation
Abstract

We predicted that the proportion of suckling attempts rejected and terminated by the mother would be greater for female foals than male foals, based on parent offspring conflict theory and on the assumption that throughout the study, all zebra mothers were in good condition because of captivity. We presumed that an increasing rate of suckling terminated or rejected by a mother would indicate a decreasing effort by the mother to invest in her offspring. We observed foals of captive plains zebras at the Dvur Kralove Zoo, Czech Republic. We found that the probability of successful suckling tended (slope = 0.0016; Z = 1.78; P = 0.074) to increase with increasing age of the female foals, but decreased (slope = -0.0018; Z = -2.51; P = 0.012) with increasing age of the male foals. The proportion of suckling bouts terminated by the mother decreased (slope = -0.0077; Z = -4.27; P < 0.0001) with increasing age of the female foals, but not the male foals (slope = -0.0005; Z = -0.34; P = 0.732). Our results indicate that conflict between mothers and female foals was less than that between mothers and male foals. The observed sex differences in termination and rejection of suckling bouts could be explained by the different behavior of the male and female foals, or by the selective maternal investment. Finally, we revealed no significant effect of herdmates on suckling behavior. Key words: mother-offspring interaction, parental investment theory, plains zebra, sex difference, zoo doi: 10.2527/jas.2009-1982

Published
2010
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16. Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage

Author

Filippi, Massimo, Rocca, Maria A, Pagani, Elisabetta, De Stefano, Nicola, Jeffery, Douglas, Kappos, Ludwig, Montalban, Xavier, Boyko, Alexei N, Comi, Giancarlo, Filippi, M, Rocca, MA, Absinta, M, Longoni, G, Galantucci, S., Pagani, E, DallʼOcchio, L., Misci, P., Petrolini, M., Sala, S., Vuotto, R., Comi, G, Boyko, A, Filippi, M, Jeffery, D, Kappos, L, Montalban, x, McFarland, H, Bauer, K, Galay, N, Weber, J, Franta, C, Lampi, C, Shotekov, P, Bozhinov, S, Deleva, N, Haralanov, L, Ivanova Hristova, S, Petrov, I, Milanov, I, Kremenchutzky, M, Rabinovitch, H, Ayotte, C, GrandMaison, F, Lamontagne, A, Leckey, R, Lee, L, Hradilek, P, Kanovsky, P, Gross-Paju, K, Taba, P, Vermersch, P, Rumbach, L, Clavelou, P, Confavreux, C, Pelletier, J, Edan, G, Shakarishvili, R, Tsiskaridze, A, Becker, E, Chan, A, Eggers, J, Haas, J, Heesen, C, Heidenreich, F, Koehler, J., Koelmel, H W, Linker, R, Oschmann, P, Rauer, S, Maschke, M, Mueller, M, Reifschneider, G, Wildemann, B, Steinbrecher, A, Tumani, H, Ziebold, U, Ziemssen, T, Kanya, J, Jakab, G, Valikovics, A, Bartos, L, Karussis, D, Rawashdeh, H, Karni, A, Chapman, J, Comi, G, Caputo, D, Centonze, D, Cottone, S, Ghezzi, A, Maimone, D, Montanari, E, Plewnia, K, Scarpini, E, Metra, M, Rastenyte, D, Sceponaviciute, S, De Jong, B, Frequin, S, Visser, L, Zwanikken, C., Selmaj, K, Blaszczyk, B., Wajgt, A, Nowak, R, Jasinska, E, Brola, W, Sobkowiak-Osinska, M, Kapustecki, J, Zaborski, J, Panea, CA, Simu, M, Bulboaca, AC, Balasa, RI, Carciumaru, N, Boyko, A, Skoromets, A, Stolyarov, I, Perfilyev, S, Odinak, M, Amelina, O, Malkova, N, Gustov, A, Volkova, L, Shutov, A, Drulovic, J, Vojinovic, S, Montalban, Arroyo, R, Saiz Hinarejos, A, Brieva, L, Ramio, L, Meca Lallana, J, Amigo Jorrin, MdC, Prieto, JM, Munoz Gracia, D, Aladro, Y, Coret, F, Escartin, A, Diez Tejedor, E, Hillert, J, Olddon, T, Martin, C, Idiman, E, Sharrack, B, Giovannoni, G, Young, C, Nehrych, T, Moskovko, S, Kobys, T, AIpatov, Loganovskyi, K, AbouZeid, N, Jeffery, D, Dihenia, B, Carpenter, A, Flitman, S, Gazda, S, Goodman, A, Green, B, Gupta, A, Herbert, J, Hughes, B, Jacobs, A, Khatri, B, Lynch, S, Miller, T, Markowitz, C, Murray, R, Pardo, G, Parry, G, Gottschalk, G, Rossman, H, Scaberry, S, Thomas, F, Turel, A, Anderson, G, CTwyman, and Wyn, D

Published
2014
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18. Preorbital gland opening in red deer (Cervus elaphus) calves: signal of hunger?

Author

Bartos, L., Vichova, J., and Lancingerova, J.

Subjects
Red deer -- Research, Zoology and wildlife conservation
Abstract

The opening of the preorbital gland in red deer (Cervus elaphus) calves has been hypothesized to be a signal to the mother that her calf is hungry. Closing of the gland should indicate that the calf has received a sufficient amount of milk, and thus the mother should stop the suckling. We tested the hypothesis that the calf signals hunger when its preorbital gland is open and signals satiation when the gland is closed. To test this, the behavior of eight bottle-reared calves was monitored for 6 mo. For each meal during this time period, opening of the preorbital gland was recorded before calves were offered the meal and after they ate. Satiation of the calf was estimated (not begging for more food after the meal = satiated; begging = not satiated). The data set contained 3,116 records of paired measurements of preorbital gland opening (before and after the meal). Calves were satiated after feeding for 90.15% of the meals. The opening of the preorbital gland was associated with feeding and achieving satiety. In most cases (77%), calves opened their preorbital glands before their meal. Eighty-five percent of hungry calves still had preorbital glands open after the meal, whereas preorbital gland opening was decreased (P < 0.03) up to 46.6% in satiated calves. Despite this, we found a large range in individual responses in preorbital gland opening before and after the meal, and also according to whether the calf reached satiety. The heavier calves in this study tended to have their preorbital glands open more frequently than the lighter ones, which may indicate the need for an increased amount of milk intake. There was no clear trend in the frequency of preorbital gland opening with age. In conclusion, preorbital opening is likely to be a signal of calf satiety, as suggested earlier. Nevertheless, preorbital glands were not always open when the calves were hungry and did not vanish during the feeding in all cases. Key Words: Cervus elaphus, Hunger, Preorbital Gland Opening, Red Deer Calves, Satiety, Signal

Published
2005

21. Technical note: Preorbital gland opening in red deer (Cervus elaphus) calves as an indicator of stress

Author

Bartosova-Vichova, J., Bartos, L., and Svecova, L.

Subjects
Red deer -- Research, Red deer -- Physiological aspects, Alarm reaction -- Research, Zoology and wildlife conservation
Abstract

The opening of the preorbital gland of red deer (Cervus elaphus) calves has been previously associated with feeding and satiety. However, it has been suggested to be most likely affected by some other factor or factors, possibly by excitement of the calf. If so, a calf should open its preorbital gland while being exposed to any stressful procedure. The hypothesis was tested that the preorbital gland is closed in a relaxed calf, whereas it is opened in a stressed calf. Preorbital opening was observed in 41 newborn red deer farm calves during a regular daily routine consisting of a search for newborn calves, their inspection, weighing, and painful marking with an ear tag. The openness of the preorbital gland (preorbital gland closed or opened) was recorded just before manipulation of a lying calf (i.e., in a calm calf) and then during the manipulation (i.e., in a distressed calf). Before manipulation, in all but 3 calves (7.3%, all of which were males), the preorbital gland was closed. All calves observed (100%) opened their preorbital gland during their manipulation, at least by the time the ear was punctured by the ear tag. The proportion of individuals with an open gland was lower (P [less than or equal to] 0.001) before than during manipulation (7.3 vs. 100%, respectively). Hence, openness of the preorbital gland in newborn red deer calves was associated with a stressful manipulation by the humans, which suggests that it may be a simple and easily recognized indicator of calf stress. Key words: Cervus elaphus, excitement, preorbital gland opening, red deer calf, stress

Published
2007

24. Phase III Dose-Comparison Study of Glatiramer Acetate for Multiple Sclerosis

Author

Comi, G, Cohen, Ja, Arnold, Dl, Wynn, D, Filippi, M, FORTE Study Group, Rocc, Ma, Perego, E, Absinta, M, Mesaros, S, Vuotto, R, Misci, P, Petrolini, M, Coyle, P, Wolinsky, J, Antel, J, Zamvil, S, Feigin, P, Carra, Aj, Bettinelli, Rj, Luetic, Gg, Vrech, Ca, Dubois, Bd, Metz, L, Bar Or, A, Bhan, V, Myles, M, Havrdova, E, Ehler, E, Kanovsky, P, Talab, R, Zapletalova, O, Gross Paju, K, Taba, P, Elovaara, I, Erälinna, Jp, Kinnunen, E, Koivisto, K, Reunanen, M, Brochet, B, Camu, W, Damier, P, Defer, G, Tumani, H, Becker, E, Buettner, T, Diener, Hc, Franz, P, Haas, J, Heesen, C, Heidenreich, F, Koelmel, Hw, Reifschneider, G, Retzlaff, K, Thoemke, F, Ziemssen, T, Rozsa, C, Bartos, L, Csanyi, A, Deme, I, Komoly, S, Panczel, G, Simo, M, Achiron, A, Milo, R, Bergamaschi, R, Bertolotto, A, Capra, R, Caputo, D, Cavalla, P, Centonze, D, Cottone, S, DE STEFANO, Nicola, Gasperini, C, Mancardi, G, Provinciali, L, Ruggieri, S, Scarpini, E, Zaffaroni, M, Metra, M, Kizlaitiene, R, Vaitkus, A, Zwanikken, Cp, Hupperts, Rm, Jongen, Pj, Szczudlik, A, Fryze, W, Kazibutowska, Z, Pierzchaa, K, Pniewski, J, Podemski, R, Stepień, A, Bajenaru, O, Campeanu, A, Marginean, I, Popescu, Cd, Toldisan, I, Boiko, A, Gustov, A, Malkova, N, Perfilyev, S, Poverennova, I, Saykhunov, M, Shutov, A, Skoromets, A, Spirin, N, Stolyarov, I, Volkova, L, Rodriguez Antigüedad, A, Arbizu, T, Arroyo, R, Barcena, J, Casanova, B, Fernández, O, Montalban, X, Ramió, L, Saiz Hinarejos, A, Sharrack, B, Silber, E, Young, C, Agius, M, Birnbaum, G, Campagnolo, D, Chaudhary, K, Cohen, J, Ford, C, Fox, E, Goodman, A, Green, B, Gupta, A, Hughes, B, Javed, A, Jeffery, D, Kasper, L, Kaufman, M, Khan, O, Kresa Reahl, K, Leist, T, Lynch, S, Markowitz, C, Mattson, D, Moses, H, Parks, B, Parry, G, Phillips, T, Picone, M, Rammohan, K, Rizvi, S, Royal, W, Scarberry, S, Sheppard, C, Simnad, V, Thrower, B, Whitham, R, Wynn, D., Comi, G, Cohen, Ja, Arnold, Dl, Wynn, D, Filippi, M, FORTE Study, Group, Diener, Hans Christoph (Beitragende*r), Klinische Neurowetenschappen, and RS: MHeNs School for Mental Health and Neuroscience

Subjects
Male, Medizin, MULTICENTER, Relapsing-Remitting, Gastroenterology, law.invention, DOUBLE-BLIND, Randomized controlled trial, law, Recurrence, Drug Toxicity, Clinical endpoint, Secondary Prevention, administration /&/ dosage/adverse effects/therapeutic use, Middle Aged, drug therapy, Intention to Treat Analysis, Treatment Outcome, Neurology, Tolerability, Disease Progression, RELAPSE RATE, TRIAL, Female, Settore MED/26 - Neurologia, Drug, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Multiple Sclerosis, Drug-Related Side Effects and Adverse Reactions, Adolescent, Endpoint Determination, DOUBLE-BLIND, RELAPSE RATE, FOLLOW-UP, DISABILITY, TRIAL, MULTICENTER, MS, Dose-Response Relationship, Multiple Sclerosis, Relapsing-Remitting, Adolescent, Adult, Disease Progression, Dose-Response Relationship, Drug, Drug Toxicity, Endpoint Determination, Female, Humans, Immunosuppressive Agents, administration /&/ dosage/adverse effects/therapeutic use, Intention to Treat Analysis, Male, Middle Aged, Multiple Sclerosis, drug therapy, Multiple Sclerosis, drug therapy, Peptides, administration /&/ dosage/adverse effects/therapeutic use, Recurrence, prevention /&/ control, Treatment Outcome, Internal medicine, medicine, Humans, Glatiramer acetate, Expanded Disability Status Scale, Intention-to-treat analysis, Peptides, Dose-Response Relationship, Drug, business.industry, DISABILITY, MS, Glatiramer Acetate, Confidence interval, Surgery, Relative risk, prevention /&/ control, Neurology (clinical), FOLLOW-UP, business
Abstract

Objective: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40mg compared to a 20mg dose. Methods: Patients with multiple sclerosis (MS) with ≥1 documented relapse in 12 months prior to screening, or ≥2 documented relapses in 24 months prior to screening, and Expanded Disability Status Scale (EDSS) score 0 to 5.5 were enrolled. Patients were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. Primary endpoint was rate of confirmed relapses observed during 12-month study. Analysis was by intent-to-treat. Results: A total of 1,155 patients randomized to GA 20mg (n = 586) or 40mg (n = 569). The groups were well-matched at baseline on demographic, clinical, and magnetic resonance imaging (MRI) characteristics. The primary endpoint was similar in both groups (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.88–1.31; p = 0.486) with mean annualized relapse rates (ARRs) of 0.33 for the 20mg group, 0.35 for the 40mg group, and 0.27 for patients from both groups who completed the entire 1-year treatment. A total of 77% of patients remained relapse-free in both groups. Both groups showed a reduction in mean number of gadolinium-enhancing and new T2 lesions over time with trend for faster reduction in the first trimester with the 40mg dose compared with 20mg dose. Both doses were well-tolerated with a safety profile similar to that observed in previous studies of 20mg GA. Interpretation: In relapsing-remitting MS patients, both the currently-approved GA 20mg and 40mg doses were safe and well-tolerated, with no gain in efficacy for the higher dose. Ann Neurol 2011;69:75–82.

Published
2011
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29. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study

Author

Khatri, B, Barkhof, F, Comi, G, Hartung, Hp, Kappos, L, Montalban, X, Pelletier, J, Stites, T, Wu, S, Holdbrook, F, Zhang auberson, L, Francis, G, Cohen, Ja, Cohen, J, Easton, Jd, Calandra, T, Dimarco, J, Hudson, L, Kesselring, J, Laupacis, A, Temkin, N, Weinshenker, B, Zarbin, M, Poppe, P, Luetic, G, Cristiano, E, Caceres, F, Garcea, O, Correale, J, Ballario, C, Piedrabuena, R, Pollard, J, Beran, R, Hodgkinson, S, Schwartz, R, Heard, R, King, J, Butzkueven, H, Maida, Em, Vass, K, Franta elmer, C, Berger, T, Aichner, F, Ladurner, G, Bissay, V, Sindic, C, D'Hooghe, M, Mulleners, E, Damasceno, B, Barreira, A, Naylor, R, Alvarenga, R, Bacellar, A, Haussen, S, Duquette, P, Antel, J, Lamontagne, A, Grand'Maison, F, Freedman, M, Christie, S, O'Connor, P, Vorobeychik, G, Devonshire, V, Ramadan, M, Hamdy, S, Reda, E, Hashem, S, Fouad, M, Lebrun frenay, C, Clanet, M, Brochet, B, Debouverie, M, Heinzlef, O, Ziemssen, T, Koehler, W, Tiel wilck, K, Bachus, R, Altmann, N, Faiss, J, Baum, K, Dressel, A, Luckner, K, Ebke, M, Stangel, M, Diener, Hc, Bethke, F, Limmroth, V, Maschke, M, Thoemke, F, Reifschneider, G, Diehm, R, Wildemann, B, Melms, A, Rauer, S, Karlbauer, G, Berthele, A, Lang, M, Tumani, H, Krauseneck, P, Klein, M, Papadimitriou, A, Karageorgiou, K, Liakopoulos, D, Tascos, N, Plaitakis, A, Papathanasopoulos, P, Panczel, G, Jakab, G, Csiba, L, Komoly, S, Csanyi, A, Bartos, L, Centonze, D, Pozzilli, C, Marrosu, Mg, Bertolotto, A, Mancardi, GIOVANNI LUIGI, Scarpini, E, Protti, A, Ghezzi, A, Capra, R, Bergamaschi, R, Gallo, P, Stecchi, S, Montanari, E, Tola, Mr, Amato, Mp, Silvestrini, M, Lugaresi, A, Trojano, M, Morra, Vb, Ruggieri, S, Patti, F, Kim, Sm, Lee, Kh, Kim, Hj, Park, Sp, Ginestal, R, Salgado, Av, Fontoura, P, Cunha, L, Sousa, L, Mj, Sá, Pedrosa, R, Arbizu, T, Arroyo, R, Merino, Ja, Fernandez, O, Izquierdo, G, Casanova, B, Antigüedad, A, Goebels, N, Young, C, Lee, M, Chaudhuri, A, Nicholas, R, Martinez, Ac, Preiningerova, J, Greco, D, Gross, J, Newman, S, Mitchell, G, Pawar, G, Freedman, Sm, Kaufman, M, Absher, J, Kantor, D, Ayala, R, Honeycutt, W, Shafer, S, Steingo, B, Delgado, S, Cascione, M, Brock, C, Keegan, A, Laganke, C, Hunter, S, Wilson, E, Mazhari, A, Bauer, W, Singer, B, Lynch, S, Rowe, V, Hutton, G, Gazda, S, Dihenia, B, Campagnolo, D, Chippendale, T, Ash, P, Jung, L, Olek, M., Radiology and nuclear medicine, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, Khatri B, Barkhof F, Comi G, Hartung HP, Kappos L, Montalban X, Pelletier J, Stites T, Wu S, Holdbrook F, Zhang-Auberson L, Francis G, Cohen JA, TRANSFORMS Study Group, Lugaresi A, Diener, Hans Christoph (Beitragende*r), Khatri, B, Barkhof, F, Comi, G, Hartung, Hp, Kappos, L, Montalban, X, Pelletier, J, Stites, T, Wu, S, Holdbrook, F, Zhang Auberson, L, Francis, G, Cohen, Ja, BRESCIA MORRA, Vincenzo, Comi, Giancarlo, TRANSFORMS Study, Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie

Subjects
Adult, Male, medicine.medical_specialty, multiple sclerosis, interferon beta, fingolimod, treatment, Multiple Sclerosis, Adolescent, Medizin, Phases of clinical research, Relapsing-Remitting, Injections, Intramuscular, Young Adult, Humans, Adjuvants, Immunologic, Interferon-beta, Immunosuppressive Agents, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, Middle Aged, Propylene Glycols, Sphingosine, Female, law.invention, Injections, Randomized controlled trial, law, Immunologic, analogs /&/ derivatives/therapeutic use, Internal medicine, Fingolimod Hydrochloride, Medicine, Adjuvants, Young adult, Intramuscular, business.industry, Multiple sclerosis, Interferon beta-1a, medicine.disease, Fingolimod, Surgery, drug therapy/pathology/physiopathology, Clinical research, therapeutic use, Adolescent, Adult, Female, Humans, Immunosuppressive Agents, therapeutic use, Injections, Intramuscular, Interferon-beta, therapeutic use, Male, Middle Aged, Multiple Sclerosis, drug therapy/pathology/physiopathology, Propylene Glycols, therapeutic use, Sphingosine, analogs /&/ derivatives/therapeutic use, Treatment Outcome, Young Adult, therapeutic use, Settore MED/26 - Neurologia, Neurology (clinical), business, medicine.drug
Abstract

In a 12-month phase 3 study in patients with relapsing-remitting multiple sclerosis (RRMS), TRANSFORMS, fingolimod showed greater efficacy on relapse rates and MRI outcomes compared with interferon beta-1a. We had two aims in our extension: to compare year 2 with year 1 in the switched patients to assess the effect of a change from interferon beta-1a to fingolimod, and to compare over 24 months the treatment groups as originally randomised to assess the effect of delaying the start of treatment with fingolimod. METHODS: Patients randomly assigned to receive 0.5 mg or 1.25 mg daily oral fingolimod in the core study continued with the same treatment in our extension; patients who originally received 30 μg weekly intramuscular interferon beta-1a were randomly reassigned (1:1) to receive either 0.5 mg or 1.25 mg fingolimod. The initial randomisation and dose of fingolimod assigned for the extension remained masked to the patients and investigators. As in the core study, re-randomisation was done centrally in blocks of six and stratified according to site. Our efficacy endpoints were annualised relapse rate (ARR), disability progression, and MRI outcomes. Our within-group analyses were based on the intention-to-treat and safety populations that entered our extension study. Our between-group analyses were based on the intention-to-treat and safety populations from the core study. This study is registered with ClinicalTrials.gov, number NCT00340834. FINDINGS: 1027 patients entered our extension and received the study drug, and 882 completed 24 months of treatment. Patients receiving continuous fingolimod showed persistent benefits in ARR (0.5 mg fingolimod [n=356], 0.12 [95% CI 0.08-0.17] in months 0-12 vs 0.11 [0.08-0.16] in months 13-24; 1.25 mg fingolimod [n=330], 0.15 [0.10-0.21] vs 0.11 [0.08-0.16]; however, in patients who initially received interferon beta-1a, ARR was lower after switching to fingolimod compared with the previous 12 months (interferon beta-1a to 0.5 mg fingolimod [n=167], 0.31 [95% CI 0.22-0.43] in months 0-12 vs 0.22 [0.15-0.31], in months 13-24 p=0.049; interferon beta-1a to 1.25 mg fingolimod [n=174], 0.29 [0.20-0.40] vs 0.18 [0.12-0.27], p=0.024). After switching to fingolimod, numbers of new or newly enlarging T2 and gadolinium (Gd)-enhancing T1 lesions were significantly reduced compared with the previous 12 months of interferon beta-1a therapy (p

Published
2011
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30. Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study

Author

Bousser, M, Amarenco, P, Chamorro, A, Fisher, M, Ford, I, Fox, K, Hennerici, M, Mattle, H, Rothwell, P, Julian, D, Fieschi, G, Fieschi, C, Boysen, G, Pocock, S, Conard, J, Orgogozo, J, Inzitari, D, Erkinjuntti, T, Pasquier, F, O'Brien, J, Mas, J, Gueret, P, Lenzi, G, Leys, D, Lopez Sendon, J, Norrving, B, Ferro, J, Thygesen, K, Cowpply, B, P, Ameriso, S, Donnan, D, Lang, W, Thijs, V, Fernandes, J, Stamenova, P, Teal, P, Lavados, P, Lu, C, Poljakovic, Z, Kalita, Z, Kaste, M, Moulin, T, Vemmos, K, Diener, H, Wong, L, Nagy, Z, Chopra, J, Mccormack, P, Gensini, G, Budrys, V, Droste, D, Tan, K, Benomar, A, Cantu Brito, C, Barber, A, Koudstaal, P, Thomassen, L, Czlonkowska, A, Cunha, L, Bajenaru, O, Yakhno, N, Chen, C, Lisy, L, Zvan, B, Bryer, A, Kim, J, Vivancos, J, Wahlgren, N, Liu, S, Poungvarin, N, Hentati, F, Bahar, S, Mischenko, T, Lees, K, Abdel Masih, M, Barboza, A, Cirio, J, Crespo, E, Escaray, G, Esnaola, M, Rojas Estol, C, Ferrari, J, Fraiman, H, Garrote, M, Gatto, E, Giannaula, R, Gori, H, Herrera, G, Ioli, P, Losano, J, Povedano Reich, E, Rey, R, Rotta Escalante, R, Saredo, G, Zurru, M, Anderson, C, Bladin, C, Crimmins, D, Davis, S, Donnan, G, Dunbabin, D, Frayne, J, Gates, P, Hankey, G, Helme, R, Herkes, G, Karrasch, J, Kimber, T, Jannes, J, Landau, P, Levi, C, Lueck, C, Markus, R, Phan, T, Schwartz, R, Schultz, D, Blacker, D, Read, S, Williams, M, Aichner, F, Auff, E, Bancher, C, Binder, H, Brainin, M, Brucke, T, Eggers, C, Fertl, E, Ladurner, G, Lalouschek, W, Mamoli, B, Mitrovic, N, Noisternig, G, Schmidt, R, Vosko, M, Willeit, J, Zaruba, E, Boon, P, Bourgeois, P, Caekebeke, J, Cals, N, Cras, P, Desfontaines, P, De Deyn, P, Dieudonne, L, De Klippel, N, Laloux, P, Maertens de Noordhout, A, Merlevede, K, Michotte, A, Pandolfo, M, Peeters, A, Peeters, D, Tack, P, Van Buggenhout, E, Van Landegem, W, Vanhooren, G, Vermylen, P, Annes, M, Brondani, R, De Carvalho, J, Cendes, F, Fabio, S, Ferraz, A, De Freitas, G, Gagliardi, R, Gomes Neto, A, Haussen, S, Kowacs, P, Martins, S, Minelli, C, Moro, C, Noujaim, J, Rocha, M, Da Silva, M, Silveira, J, Yamamoto, F, Zetola, V, Baldaranov, D, Deleva, N, Haralanov, L, Milanov, I, Mintchev, D, Petrova, N, Shotekov, P, Stamenov, B, Zahariev, Z, Arts, R, Bayer, N, Beaudry, M, Berger, L, Bozek, C, Collier, T, Cote, R, Desai, H, Durocher, A, Hachinski, V, Hill, M, Hoppe, B, Howse, D, Mackey, A, Maharaj, M, Minuk, J, Moddel, G, Novak, D, Penn, A, Rabinovitch, H, Selchen, D, Shuaib, A, Silva, J, Silver, F, Spence, D, Stotts, G, Tamayo, A, Teitelbaum, J, Veloso, F, Voll, C, Winder, T, Barrientos Uribe, N, Galdames Poblete, D, Garcia Figueroa, P, Gasic Yaconi, K, Jaramillo Munoz, A, Lavados Germain, P, Lavados Montes, M, Nancupil Bello, C, Prina Pacheco, L, Vargas Canas, A, Venegas, F, Chen, P, H, Cheng, Y, Cui, L, Di, Q, Dong, Q, Fan, D, Feng, H, Huang, Y, Li, J, Li, W, Li, Z, Lin, H, Liu, M, Miao, L, Ren, H, Wang, Y, Wu, J, Zhang, W, Zhao, G, Zhao, H, Zhou, H, Antoncic, I, Demarin, V, Lusic, I, Pavlicek, I, Soldo Butkovic, S, Bar, M, Bauer, J, Kalina, M, Kanovsky, P, Jura, R, Neumann, J, Rektor, I, Skoda, O, Vaclavik, D, Eerola, A, Hillbom, M, Kinnunen, E, Koivisto, K, Numminen, H, Rissanen, A, Roine, R, Sivenius, J, Alamowitch, S, Autret, A, Avendano, S, Bataillard, M, Berthier, E, Besson, G, Bille Turc, F, Boulliat, J, Boulesteix, J, Brosset, C, Cesaro, P, Albucher, J, Clavelou, P, Colamarino, R, Crassard, I, de Broucker, T, de Bray, J, Desbordes, P, Diot, E, Ducrocq, X, Ellie, E, Faucheux, J, Giroud, M, Godefroy, O, Guillon, B, Huttin, H, Just, A, Lamy, C, Lejeune, P, Lucas, C, Macian Montoro, F, Mackowiak, A, Maillet Vioud, M, Pico, F, Milandre, L, Milhaud, D, Malbec, M, Neau, J, Pinel, J, Robin, C, Rodier, G, Rosolacci, T, Rouanet, F, Rouhart, F, Sablot, D, Servan, J, Smadja, D, Trouillas, P, Valance, J, Viader, F, Viallet, F, Wolff, V, Zagnoli, F, Zuber, M, Angerer, M, Becker, U, Berlit, P, Berrouschot, J, Biniek, R, Bitsch, A, Brodhun, R, Dichgans, M, Druschky, K, Dux, R, Faiss, J, Ferbert, A, Gahn, G, Grotemeyer, K, Goertler, M, Grau, A, Griewing, B, Grond, M, Haan, J, Haberl, R, Hamann, G, Hamer, H, Harms, L, Heide, W, Henningsen, H, Hetzel, A, Hoffmann, F, Huber, R, Isenmann, S, Jander, S, Joerg, J, Kaps, M, Kastrup, A, Kessler, C, Koehler, W, Koelmel, H, Lichy, C, Luckner, K, Malessa, R, Mallmann, A, Meyding Lamade, U, Molitor, H, Mueller Jensen, A, Muellges, W, Noth, J, Nueckel, M, Ochs, G, Poppert, H, Roether, J, Rosenkranz, M, Sander, D, Schaebitz, W, Schlachetzki, F, Schlegel, U, Schmid, E, Schneider, D, Schwarz, M, Seidel, G, Sieble, M, Sliwka, U, Stingele, R, Stoegbauer, F, Szabo, K, Topper, R, Treib, J, Weissenborn, K, Widder, B, Witte, O, Karageorgiou, K, Mitsikostas, D, Papadimitriou, A, Papathanasopoulos, P, Chan, H, Ng, P, Tsoi, T, Bartos, L, Csanyi, A, Csiba, L, Csornai, M, Dioszeghy, P, Fazekas, A, Harcos, P, Horvath, S, Kaposzta, Z, Kerenyi, L, Kincses, J, Koves, A, Nikl, J, Panczel, G, Pongracz, E, Sebestyen, K, Semjen, J, Szabo, M, Szegedi, N, Valikovics, A, Varszegi, R, Vecsei, L, Borah, N, Ichaporia, N, Kaul, S, Meenakshi Sundaram, S, Mehndiratta, M, Misra, U, Murthy, J, Nayak, D, Poncha, F, Shah, A, Singh, G, Srinivasa, R, Venkateswarlu, K, Wadia, R, Collins, R, Harbison, J, Hickey, P, Kelly, P, Murphy, S, Adami, A, Agnelli, G, Agostoni, E, Anzola, G, Arnaboldi, M, Bassi, P, Billo, G, Bottacchi, E, Bovi, P, Cappa, S, Cappelletti, C, Carolei, A, Cavallini, A, Chiodo Grandi, F, Comi, G, Consoli, D, Corsi, F, Costanzo, E, De Falco, F, Devetag, F, Di Lazzaro, V, Di Piero, V, Diomedi, M, Fattorello Salimbeni, C, Federico, F, Feleppa, M, Ferrarese, C, Gandolfo, C, Giaccaglini, E, Giaquinto, S, Giobbe, D, Giometto, B, Greco, G, Guidetti, D, Guidotti, M, Iudice, A, Lembo, G, Marengo, C, Marini, P, Melis, M, Micieli, G, Musolino, R, Mutani, R, Neri, G, Parati, E, Pastore, L, Porazzi, D, Prati, P, Procaccianti, G, Rasura, M, Rossini, P, Santilli, I, Semplicini, A, Silvestrini, M, Tanganelli, P, Tedeschi, G, Tezzon, F, Tola, M, Villani, A, Zanferrari, C, Zarcone, D, Bickuviene, I, Gumbrevicius, G, Obelieniene, D, Skaringa, A, Virketiene, I, Tharakan, J, Aleman Pedroza, J, Escamilla Garza, J, Fernandez Vera, J, Leal Cantu, R, Leon Flores, L, Lopez Ruiz, M, Reyes Gutierrez, G, Reyes Morales, S, Rivera Castano, L, Rodrigues Leyva, I, Ruiz Sandoval, J, Vega Boada, F, Belahsen, F, Kissani, N, Mosseddaq, R, Slassi, I, Yahyaoui, M, Boiten, J, Bornebroek, M, De Kort, P, De Leeuw, H, Donders, R, Franke, C, Hertzberger, L, Jansen, B, Kappelle, L, Keizer, K, Kuster, J, Limburg, M, Mulleners, W, Pop, P, Van Den Berg, J, Van Gemert, H, Verbiest, H, Weinstein, H, Clark, M, Fink, J, Gommans, J, Jayathissa, S, Kilfoyle, D, Kumar, A, Hurtig, U, Indredavik, B, Kloster, R, Salvesen, R, Drozdowski, W, Fryze, W, Klimek, A, Kochanowski, J, Kozubski, W, Ksiazkiewicz, B, Kwiecinski, H, Kuczynska Zardzewialy, A, Motta, E, Nowacki, P, Nyka, W, Opala, G, Pierzchala, K, Pniewski, J, Podemski, R, Selmaj, K, Stelmasiak, Z, Stepien, A, Strzelecka Gorzynska, M, Szczudlik, A, Wajgt, A, Wiszniewska, M, Wlodek, A, Canhao, P, Correia, C, Grilo Goncalves, J, Machado Candido, J, Salgado, A, Bulboaca, A, Campeanu, A, Lazar, T, Marginean, I, Minea, D, Pascu, I, Pereanu, M, Perju Dumbrava, L, Popescu, C, Simu, M, Stefanache, F, Toldisan, I, Tuta, S, Zaharia, C, Alifirova, V, Arkhipov, S, Balunov, O, Balyazin, V, Belkin, A, Belova, A, Boiko, A, Bogdanov, E, Butko, D, Chukhlovina, M, Doronin, B, Ermilova, E, Evzelman, M, Fedin, A, Fedorova, N, Golikov, K, Golovkin, V, Gusev, E, Gustov, A, Jakupov, E, Kamchatnov, P, Khabirov, F, Kirienko, A, Klimov, I, Klocheva, E, Kotov, S, Kuznetsov, A, Laskov, V, Levin, Y, Mashkova, N, Nazarov, A, Novikova, L, Odinak, M, Parfenov, V, Pilipenko, P, Pokrovsky, A, Poverennova, I, Rodoman, G, Roshkovskaya, L, Shirokov, E, Shmyriov, V, Sholomov, I, Skoromets, A, Skvortsova, V, Spirin, N, Stakhovskaya, L, Sharov, M, Sherman, M, Shutov, A, Strachunskaya, E, Stulin, I, Suslina, Z, Volosevitch, A, Vorobiev, P, Vorobyeva, O, Voronkova, L, Voskresenskaya, O, Zhuliov, N, Chan, B, Chang, H, Ramani, N, Brozman, M, Dvorak, M, Dzugan, J, Garay, R, Gdovinova, Z, Gurcik, L, Krastev, G, Kukumberg, P, Kurca, E, Meluch, S, Nyeky, M, Turcani, P, Vyletelka, J, Klanjscek, G, Zujovic, E, Zupan, M, Bester, F, Carr, J, Coetzee, C, Frost, A, Gardiner, J, Giampaolo, D, Kesler, S, Lurie, D, Retief, C, Roos, J, Bae, H, Cha, J, Cho, K, Heo, J, Kim, E, Lee, B, Lee, K, Lee, J, Rha, J, Yoon, B, Alvarez Sabin, J, Arboix Damunt, A, De Arce Borda, A, Asensi Alvarez JM, Bermejo Pareja, F, Botia Paniagua, E, Casado, I, Naranjo, I, Castillo Sanchez, J, Chamorro Sanchez, A, Davalos Errando, A, Diaz Marin, C, Diez Tejedor, E, Egido Herrero JA, Fernandez Bolanos, R, Fernandez Fernandez, O, Figuerola Roig, A, Geffner Sclarsky, D, Gil Nunez, A, Gomez Sanchez JC, Gomez Escalonilla Escobar CI, Gonzalez Masegosa, A, Gonzalez Menacho, J, Gracia Fleta, F, Izquierdo Ayuso, G, Jimenez Hernandez, D, Jimenez Martinez, C, Lago Martin, A, Lainez Andres JM, Larracoechea Jausoro, J, Lopez Fernandez JC, Maestre Moreno, J, Marti Vilalta JL, Martin Gonzalez, R, Masjuan Vallejo, J, Medina Rodriguez, A, Molto Jorda JM, Moreno Carre tero MJ, Moris de le Tassa, G, Morlan Gracia, L, Mostacero Miguez, E, Osuna Pulido, T, Pareja Martinez, A, Pinedo Brochado, A, Pons Amate JM, Rodriguez Alvarez JR, Roquer Gonzalez, J, Sanahuja Montesinos, J, Sanchez Sanchez MC, Segura Martin, T, Serena Leal, J, Tejada Garcia, J, Trejo Gabriel JM, Vivancos Mora, J, Andersson, B, Bysell, S, Cederin, B, Laska, A, Lindgren, A, Petersson, T, Wallen, T, Baumgartner, R, Beer, H, Hirt, L, Hungerbuehler, H, Lyrer, P, Michel, P, Mueller, F, Tettenborn, B, Chang, K, Jeng, J, Lien, L, Lin, R, Liu, C, Po, H, Wu, S, Chankrachang, S, Laptikultham, S, Nidhinandana, S, Pongpakdee, S, Benammou, S, Frih Ayed, M, Gouider, R, Mhiri, C, M'Rabet, A, Mrissa, R, Balkan, S, Can, U, Dalkara, T, Kirbas, D, Kumral, E, Ozdemir, G, Ozeren, A, Ozmenoglu, M, Ozturk, S, Lebedynets, V, Maly, V, Moskovko, S, Orzheshkovskyy, V, Smolanka, V, Yavors'Ka, V, Zozulya, I, Bamford, J, Barber, M, Barer, D, Baron, J, Bath, P, Broughton, D, Brown, M, Chataway, J, Curless, R, Darawil, K, Datta, P, Dennis, M, Durairaj, R, Egbuji, J, Ellis, S, Ford, G, Freeman, A, Fulcher, R, Gray, C, Harrington, F, Hudson, C, Iveson, E, James, M, Jenkinson, D, Kalra, L, Kelly, D, Krishnamoorthy, S, Langhorne, P, Magorrian, M, Macleod, M, Macwalter, R, Markus, H, Muhiddin, K, Muir, K, Murphy, P, Power, M, Price, C, Rashed, K, Robinson, T, Rudd, A, Sanmuganathan, P, Sharma, J, Shaw, L, Shetty, H, Smithard, D, Tyrrell, P, Vahidassr, M, Venables, G, Watt, M, White, R, Bousser, M, Amarenco, P, Chamorro, A, Fisher, M, Ford, I, Fox, K, Hennerici, M, Mattle, H, Rothwell, P, Ferrarese, C, PERFORM study, I, PERFORM STUDY, Investigator, Tedeschi, Gioacchino, Cras, Patrick, De Deyn, Peter Paul, and et al.

Subjects
perform study, Male, Thromboxane, International Cooperation, Receptors, Thromboxane, antiplatelet therapy, terutroban, Cardiovascular Disease, Receptors, 80 and over, Stroke, Aged, 80 and over, Aspirin, Ischemic Attack, Transient, Ischemic Attack, Transient, Double-Blind Method, Endpoint Determination, Dose-Response Relationship, Drug, Humans, Aged, Propionates, Naphthalenes, Treatment Outcome, Platelet Aggregation Inhibitors, Cardiovascular Diseases, Middle Aged, Female, Propionic Acids, Neurology, Terutroban, Anesthesia, tp receptor antagonist, stroke, secondary prevention, aspirin, Cardiology, Platelet aggregation inhibitor, Settore MED/26 - Neurologia, stroke prevention, Drug, Cardiology and Cardiovascular Medicine, medicine.drug, Human, medicine.medical_specialty, Dose-Response Relationship, Internal medicine, medicine, Dementia, In patient, business.industry, Platelet Aggregation Inhibitor, schemic, medicine.disease, DementiaI, transient ischemic attack, Ischemic stroke, Human medicine, Neurology (clinical), business, Propionic Acid, Naphthalene
Abstract

Background: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. Methods and Results: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged ≥55 years, having suffered an ischemic stroke (≤3 months) or a transient ischemic attack (≤8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2–4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. Conclusions: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Published
2009
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31. Short-term combination of glatiramer acetate with i.v. steroid treatment preceding treatment with GA alone assessed by MRI-disease activity in patients with relapsing-remitting multiple sclerosis

Author

De Stefano, N, Filippi, M, Hawkins, C, Rózsa, C, Kanta, E, Lehel, G, Zsigmond, I, Kocher, I, Gedeonné, J, Pozsar, K, Fornádi, L, Barsi, P, Szirmai, I, Gyorgyne, K, Simo, M, Dobos, E, Katona Kollerne, I, Harcos, P, Bajzik, G, Deme, I, Kopa, J, Gyozone, K, Bogner, P, Tokai, R, Gyorbiro, Z, Toth, E, Szatmari, F, Kiraly, H, Fejes, K, Bartos, L, Imre, P, Kovacs, Z, Guseo, A, Jofeju, E, Fritz, M, Persico, A, Romani, A, Pichiecchio, A, Uggetti, C, DagradiLaura Greppi, D, Tosetti, L, D'Amario, M, Bergamaschi, R, Bastianello, S, Cosi, V, Cordioli, C, Mardighian, D, Colleoni, Ml, Niccolai, M, Frigerio, M, Gasparotti, R, Capra, R, Pardatscher, S, Cipolletta, A, Gasperini, C, Casavecchia, E, Cantillo, E, Luccichenti, G, Fele, Mr, Galgani, S, Cartechini, E, Pucci, E, Conti, G, Giuliani, G, Pompili, Gs, Provinciali, L, Regnicolo, L, Imperiale, L, Cola, M, Danni, M, Herber, N, Arabi, S, Tarabelli, T, Salvolini, U, Andreotti, A, Guidi, L, Stromillo, Ml, Bartolozzi, Ml, Mortilla, M, Brogi, S, Murariu, A, Gogu, A, Bejenaru, D, Onet, D, Birsasteanu, F, Stoita, F, Dragota, I, Simu, M, Pavel, A, Dumitru, C, Tiu, C, Repede, F, Iana, G, Ionescu, H, Ungureanu, M, Bajenaru, O, Petrescu, S, Treaba, A, Iakob, C, Pascu, I, Szasz, J, Buruian, M, Petruta Oroian, M, Balasa, R, Constantin, V, Balint, C, Popescu, C, Pop, C, Popescu, D, Preda, D, Stanca, D, Marginean, I, Perju Dumbrava, L, Rusu, M, Rus, M, Sfringeu, S, Fischer, T, Vacaras, V, Lockett Jones, D, Mamutse, G, Stone, M, Morris, R, Williams, R, Hurlstone, S, Mihalova, T, Kidd, D, Hobro, D, Gavan, D, Moody, H, Tidswell, P, Townson, R, Sharrack, B, Taylor, C, Bowen, J, Craven, P, Malcolm, P, Gaughan, S, Houston, G, O'Riordan, J, Shah, Ps, Wilson, S, Carson, S, Brunton, T, Milne, W, Marino, Silvia, Giorgio, A, Balistreri, A, Battaglini, M, and Filippi, M.

Published
2008

40. Preorbital gland opening in red deer (Cervus elaphus) calves: 0 1 Signal of hunger?1 .

Author

Bartos, L., Vichova, J., and Lancingerova, J.

Subjects
*RED deer, *CALVES, *ANIMAL nutrition, *MILKING, *HUNGER, *MILK
Abstract

The opening of the preorbital gland in red deer (Cervus elaphus) calves has been hypothesized to be a signal to the mother that her calf is hungry. Closing of the gland should indicate that the calf has received a sufficient amount of milk, and thus the mother should stop the suckling. We tested the hypothesis that the calf signals hunger when its preorbital gland is open and signals satiation when the gland is closed. To test this, the behavior of eight bottle-reared calves was monitored for 6 mo. For each meal during this time period, opening of the preorbital gland was recorded before calves were offered the meal and after they ate. Satiation of the calf was estimated (not begging for more food after the meal = satiated; begging = not satiated). The data set contained 3,116 records of paired measurements of preorbital gland opening (before and after the meal). Calves were satiated after feeding for 90.15% of the meals. The opening of the preorbital gland was associated with feeding and achieving satiety. In most cases (77%), calves opened their preorbital glands before their meal. Eighty-five percent of hungry calves still had preorbital glands open after the meal, whereas preorbital gland opening was decreased (P < 0.03) up to 46.6% in satiated calves. Despite this, we found a large range in individual responses in preorbital gland opening before and after the meal, and also according to whether the calf reached satiety. The heavier calves in this study tended to have their preorbital glands open more frequently than the lighter ones, which may indicate the need for an increased amount of milk intake. There was no clear trend in the frequency of preorbital gland opening with age. In conclusion, preorbital opening is likely to be a signal of calf satiety, as suggested earlier. Nevertheless, preorbital glands were not always open when the calves were hungry and did not vanish during the feeding in all cases. [ABSTRACT FROM AUTHOR]

Published
2005

41. Preorbital gland opening in red deer (Cervus elaphus) calves: 0 1 Signal of hunger?1 .

Author

Bartos, L., Vichova, J., and Lancingerova, J.

Subjects
RED deer, CALVES, ANIMAL nutrition, MILKING, HUNGER, MILK
Abstract

The opening of the preorbital gland in red deer (Cervus elaphus) calves has been hypothesized to be a signal to the mother that her calf is hungry. Closing of the gland should indicate that the calf has received a sufficient amount of milk, and thus the mother should stop the suckling. We tested the hypothesis that the calf signals hunger when its preorbital gland is open and signals satiation when the gland is closed. To test this, the behavior of eight bottle-reared calves was monitored for 6 mo. For each meal during this time period, opening of the preorbital gland was recorded before calves were offered the meal and after they ate. Satiation of the calf was estimated (not begging for more food after the meal = satiated; begging = not satiated). The data set contained 3,116 records of paired measurements of preorbital gland opening (before and after the meal). Calves were satiated after feeding for 90.15% of the meals. The opening of the preorbital gland was associated with feeding and achieving satiety. In most cases (77%), calves opened their preorbital glands before their meal. Eighty-five percent of hungry calves still had preorbital glands open after the meal, whereas preorbital gland opening was decreased (P < 0.03) up to 46.6% in satiated calves. Despite this, we found a large range in individual responses in preorbital gland opening before and after the meal, and also according to whether the calf reached satiety. The heavier calves in this study tended to have their preorbital glands open more frequently than the lighter ones, which may indicate the need for an increased amount of milk intake. There was no clear trend in the frequency of preorbital gland opening with age. In conclusion, preorbital opening is likely to be a signal of calf satiety, as suggested earlier. Nevertheless, preorbital glands were not always open when the calves were hungry and did not vanish during the feeding in all cases. [ABSTRACT FROM AUTHOR]

Published
2005

42. FACTORS AFFECTING SALINITY REDUCTION IN LAKE TARPON, PINELLAS COUNTY, FLORIDA.

Author

Dooris, P. M. and Bartos, L. F.

Abstract

BSTRACT: Following an enclosure of a sink-hole connecting Lake Tarpon to the Gulf of Mexico, the chloride concentration of lake waters decreased. Water and chloride budgets for the lake in 1975 were prepared, and predictions using the model of Lerman and Brunskill (1971) were made as to the time required for the lake to achieve fresh water status. Model verification indicated good agreement with predictions in 1976; however, data on [C1 [ABSTRACT FROM AUTHOR]

Published
1980
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43. Patterns of cyprinid migration through a fishway in relation to light, water temperature and fish circling behaviour

Author

Prchalova, M., Slavik, O., and Bartos, L.

Abstract

Patterns of cyprinid migration were studied in a fishway located at a lock on the Elbe River, Czech Republic, weekly from spring to fall 2003. 24 hrs observations of fish were made with a Riverwatcher Fishcounter manufactured by Vaki (Iceland). The counter records revealed distinct diel patterns of migration. During spring, fish migrated mostly during the light part of a day, in summer and fall this pattern changed. Water temperature and illumination intensity were found as the major driving forces initiating spawning migration and controlling its development and diel pattern. This hypothesis was verified by significant influence of interaction of weather and atmospheric pressure on the number of migrating fish. Because circling of fish within a pool and between adjacent pools of the fishway was a common behavioural pattern, overestimates offish migration acitivity occurred, especially in the downstream direction. These results point out that circling behaviour and the effect of weather condition on fish migration should be taken into account in every fishway monitoring effort.

Published
2006
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44. Human bactericidal antibody response to outer membrane protein P2 of nontypeable Haemophilus influenzae

Author

Murphy, T F and Bartos, L C

Abstract

The human bactericidal antibody response to the major outer membrane protein, P2, of nontypeable Haemophilus influenzae was studied. P2 was isolated from two strains of nontypeable H. influenzae and coupled to affinity columns. Pooled normal human serum was subjected to affinity chromatography with the P2 columns and a control column. Reducing the titer of antibody to P2 resulted in reduced bactericidal activity of that serum for the organism. Immunopurified antibody to P2 from human serum was bactericidal for the homologous strain. The extent to which these bactericidal determinants on P2 are conserved among strains was investigated. Immunopurified antibodies to P2 of two epidemiologically unrelated isolates were bactericidal for four of six strains tested. We conclude that P2 is a target for human bactericidal antibody and that some of these determinants that are recognized by human bactericidal antibody are conserved among strains of nontypeable H. influenzae.

Published
1988
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45. Surface-exposed and antigenically conserved determinants of outer membrane proteins of Branhamella catarrhalis

Author

Murphy, T F and Bartos, L C

Abstract

The outer membrane proteins (OMPs) of Branhamella catarrhalis were studied in an effort to identify surface-exposed determinants that are conserved among strains of the bacterium. Aliquots of polyclonal antiserum were absorbed individually by strains of B. catarrhalis. The absorbed antisera were tested in comparison with unabsorbed antiserum in an immunoblot assay against OMPs of the homologous strain. The absence of a band recognized by antibodies in the absorbed antiserum compared with the unabsorbed antiserum indicated that surface-exposed determinants of the absorbing strain cross-reacted with determinants on the homologous strain. Two antisera were absorbed individually by 20 strains of B. catarrhalis, and the absorbed sera were studied in this way in immunoblot assays. OMP E (molecular weight, ca. 56,000) expresses surface-exposed determinants that are shared among 17 of the 20 strains studied. Antibodies to OMP G (molecular weight, 28,000) were absorbed from both antisera by 14 of the 20 strains. These studies demonstrate that OMP E and OMP G express determinants that are exposed on the surface of the intact bacterium. Furthermore, these determinants are antigenically conserved among a majority of strains of B. catarrhalis. On the basis of these observations, OMPs E and G should be considered when bacterial antigens are evaluated as potential vaccine candidates.

Published
1989
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46. Purification and analysis with monoclonal antibodies of P2, the major outer membrane protein of nontypable Haemophilus influenzae

Author

Murphy, T F and Bartos, L C

Abstract

The protein P2 comprises a large proportion of the outer membrane of nontypable Haemophilus influenzae and functions as a porin. In view of the importance of the protein as a surface antigen, the present study was designed to purify and analyze P2 with particular emphasis on detection of antigenic determinants expressed on the bacterial surface and identification of bactericidal targets on P2. The P2 protein was purified by using detergent solubility, anion-exchange chromatography, and gel-filtration chromatography sequentially. Two monoclonal antibodies to P2 were developed. One antibody (2E6) recognized a determinant expressed on the bacterial surface, whereas the other antibody (3F3) recognized an internal epitope. The surface-exposed 2E6 determinant was present on 12% of strains from a nationwide collection. P2 is a bactericidal target for antibody 2E6. Cyanogen bromide cleavage of P2 resulted in two fragments, as in type b strains. Both monoclonal antibodies recognized epitopes on the larger fragment. These observations have potentially important implications regarding the development of vaccines to prevent H. influenzae infections and the development of a serotyping system for epidemiologic studies.

Published
1988
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47. Antigenic characterization of the P6 protein of nontypable Haemophilus influenzae

Author

Murphy, T F, Bartos, L C, Campagnari, A A, Nelson, M B, and Apicella, M A

Abstract

The purpose of this study was to characterize the degree of antigenic heterogeneity or conservation of a 16,600-dalton outer membrane protein (P6) among strains of nontypable Haemophilus influenzae. Immunization of rabbits with P6 isolated from individual strains resulted in antibody to P6 of all 25 strains tested. The titers of antibody in the sera were similar among the strains. Whole organisms of two strains were used to immunize rabbits, and antibodies were produced to P6 of all strains tested. Monoclonal antibodies developed to P6 from mice immunized with whole cells of three different strains recognized determinants on P6 of all 25 strains tested. Finally, pooled normal human serum contained antibodies to P6 of all 25 strains assayed. These studies indicate that P6 is a highly conserved antigen on the outer membrane of nontypable H. influenzae.

Published
1986
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