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2. 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial

Author

Halliday, A, Harrison, M, Hayter, E, Kong, X, Mansfield, A, Marro, J, Pan, H, Peto, R, Potter, J, Rahimi, K, Rau, A, Robertson, S, Streifler, J, Thomas, D, Fraedrich G, Asymptomatic Carotid Surgery Trial Collaborative G. r. o. u. p., Schmidauer, C, Hölzenbein, Th, Huk, I, Haumer, M, Kretschmer, G, Metz, V, Polterauer, P, Teufelsbauer, H, Cras, P, Hendriks, J, Lauwers, P, Van Schil, P, de Souza EB, Dourado, Me, Gurgel, G, Rocha, Gm, Petrov, V, Slabakov, G, Cooper, Me, Gubitz, G, Holness, R, Howes, W, Langille, R, Legg, K, Nearing, S, Mackean, G, Mackay, M, Phillips, Sj, Sullivan, J, Wood, J, Erdelez, L, Sosa, T, Angelides, Ns, Christopoulos, G, Malikidou, A, Pesta, A, Ambler, Z, Mracek, J, Polivka, J, Rohan, V, Sevcik, P, Simaná, J, Benes, V, Kramár, F, Kaste, M, Lepäntalo, M, Soinne, L, Cardon, Jm, Legalou, A, Gengenbach, B, Pfadenhauer, K, Wölfl, Kd, Flessenkämper, I, Klumpp, Bf, Marsch, J, Kolvenbach, R, Pfeiff, T, Sandmann, W, Beyersdorf, F, Hetzel, A, Sarai, K, Schöllhorn, J, Spillner, G, Lutz, Hj, Böckler, D, Maeder, N, Busse, O, Grönniger, J, Haukamp, F, Balzer, K, Knoob, Hg, Roedig, G, Virreira, L, Franke, S, Moll, R, Schneider, J, Dayantas, J, Sechas, Mn, Tsiaza, S, Kiskinis, D, Apor, A, Dzinich, C, Entz, L, Hüttl, K, Jàrànyi, Z, Mogan, I, Nagy, Z, Szabo, A, Varga, D, Juhász, G, Mátyás, L, Hutchinson, M, Mehigan, D, Aladjem, Z, Harah, E, Elmakias, S, Gurvich, D, Yoffe, B, Ben Meir, H, Dagan, L, Karmeli, R, Keren, G, Shimony, A, Weller, B, Avrahami, R, Koren, R, Streifler, Jy, Tabachnik, S, Zelikovski, A, Angiletta, D, Federico, F, Impedovo, G, Marotta, V, Pascazio, L, Regina, G, Andreoli, A, Pozzati, E, Bonardelli, S, Giulini, Sm, Guarneri, B, Caiazzo, P, Mascoli, F, Becchi, G, Masini, R, Santoro, E, Simoni, G, Ventura, M, Scarpelli, P, Spartera, C, Arena, O, Collice, M, Puttini, M, Romani, F, Santilli, I, Segramora, V, Sterzi, R, Deriu, G, Verlato, F, Cao, Pg, Cieri, Enrico, De Rango, P, Moggi, L, Ricci, S, Antico, A, Spigonardo, F, Malferrari, G, Tusini, N, Vecchiati, E, Cavallaro, A, Kasemi, H, Marino, M, Sbarigia, E, Speziale, F, Zinicola, N, Alò, Fp, Bartolini, M, Carbonari, L, Caporelli, S, Grili Cicilioni, C, Lagalla, G, Ioannidis, G, Pagliariccio, G, Silvestrini, M, Palombo, D, Peinetti, F, Adovasio, R, Chiodo Grandi, F, Mase, G, Zamolo, F, Fregonese, V, Gonano, N, Mozzon, L, Blair, R, Chuen, J, Ferrar, D, Garbowski, M, Hamilton, Mj, Holdaway, C, Muthu, S, Shakibaie, F, Vasudevan, Tm, Kroese, A, Slagsvold, Ce, Dahl, T, Johnsen, Hj, Lange, C, Myhre, Ho, Gniadek, J, Andziak, P, Elwertowski, M, Leszczynski, J, Malek, Ak, Mieszkowski, J, Noszczyk, W, Szostek, M, Toutounchi, S, Correia, C, Pereira, Mc, Akchurin, Rs, Flis, V, Miksic, K, Stirn, B, Tetickovic, E, Cairols, M, Capdevila, Jm, Iborra Ortega, E, Obach, V, Riambau, V, Vidal Barraquer, F, Vila Coll, R, Diaz Vidal, E, Iglesias Negreia JI, Tovar Pardo, A, Iglesias, Rj, Alfageme, Af, Barba Velez, A, Estallo Laliena, L, Garcia Monco JC, Gonzalez, Lr, Corominas, C, Julia, J, Lozano, P, Marti Masso JF, Porta, Rm, Carrera, Ar, Gomez, J, Blomstrand, C, Gelin, J, Holm, J, Karlström, L, Mattsson, E, Bornhov, S, Dahlstrom, J, De Pedis, G, Jensen, Sm, Pärsson, H, Plate, G, Qvarfordt, P, Arvidsson, B, Brattström, L, Forssell, C, Potemkowski, A, Skiöldebrand, C, Stoor, P, Blomqvist, M, Calander, M, Lundgren, F, Almqvist, H, Norgren, L, Norrving, B, Ribbe, E, Thörne, J, Gottsäter, A, Mätzsch, T, Nilsson, Me, Lonsson, M, Stahre, B, Stenberg, B, Konrad, P, Jarl, L, Lundqvist, L, Olofsson, P, Rosfors, S, Swedenborg, J, Takolander, R, Bergqvist, D, Ljungman, C, Kniemeyer, Hw, Widmer, Mk, Kuster, R, Kaiser, R, Nagel, W, Sege, D, Weder, B, De Nie, J, Doelman, J, Yilmaz, N, Buth, J, Stultiens, G, Boiten, J, Boon, A, van der Linden, F, Busman, Dc, Sinnige, Ha, Yo, Ti, de Borst GJ, Eikelboom, Bc, Kappelle, Lj, Moll, F, Dortland, Rw, Westra, Te, Jaber, H, Manaa, J, Meftah, Rb, Nabil, Br, Sraieb, T, Bateman, D, Budd, J, Horrocks, M, Kivela, M, Shaw, L, Walker, R, D'Sa, Aa, Fullerton, K, Hannon, R, Hood, Jm, Lee, B, Mcguigan, K, Morrow, J, Reid, J, Soong, Cv, Simms, M, Baird, R, Campbell, M, Cole, S, Ferguson, It, Lamont, P, Mitchell, D, Sassano, A, Smith, Fc, Blake, K, Kirkpatrick, Pj, Martin, P, Turner, C, Clegg, Jf, Crosley, M, Hall, J, De Cossart, L, Edwards, P, Fletcher, D, Rosser, S, Mccollum, Pt, Davidson, D, Levison, R, Bradbury, Aw, Chalmers, Rt, Dennis, M, Murie, J, Ruckley, Cv, Sandercock, P, Campbell, Wb, Frankel, T, Gardner Thorpe, C, Gutowski, N, Hardie, R, Honan, W, Niblett, P, Peters, A, Ridler, B, Thompson, Jf, Bone, I, Welch, G, Grocott, Ec, Overstall, P, Aldoori, Mi, Dafalla, Be, Bryce, J, Clarke, C, Ming, A, Wilkinson, Ar, Bamford, J, Berridge, D, Scott, J, Abbott, Rj, Naylor, R, Harris, P, Humphrey, P, Adiseshiah, M, Aukett, M, Baker, D, Bishop, Cc, Boutin, A, Brown, M, Burke, P, Burnand, Kg, Colchester, A, Coward, L, Davies, Ah, Espasandin, M, Giddings, Ae, Hamilton, G, Judge, C, Kakkos, S, Mcguiness, C, Morris Vincent, P, Nicolaides, A, Padayachee, Ts, Riordan, H, Sullivan, E, Taylor, P, Thompson, M, Wolfe, Jh, Mccollum, Cn, O'Neill, Pa, Welsh, S, Barnes, J, Cleland, P, Davis, M, Gholkar, A, Jones, R, Jaykishnam, V, Mendelow, Ad, O'Connell, Je, Siddique, Ms, Stansby, G, Vivar, R, Ashley, S, Cosgrove, C, Gibson, J, Wilkins, Dc, Chant, Ad, Frankel, J, Shearman, Cp, Williams, J, Hall, G, Holdsworth, R, Davies, Jn, Mclean, B, Woodburn, Kr, Brown, G, Curley, P, Loizou, L, Chaturvedi, S, Diaz, F, Radak, D, Todorovic, Pr, Kamugasha, D, Baxter, A, Berry, C, Burrett, J, Collins, R, Crowther, J, Davies, C, Farrell, B, Godwin, J, Gray, R, Harwood, C, Hirt, L, Hope, C, Knight, S, Lay, M, Munday, A, Murawska, A, Peto, Cg, Radley, A, Richards, S., Cras, Patrick, van Schil, Paul, et al., Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group, Halliday, A, Harrison, M, Hayter, E, Kong, X, Mansfield, A, Marro, J, Pan, H, Peto, R, Potter, J, Rahimi, K, Rau, A, Robertson, S, Streifler, J, Thomas, D, Adovasio, Roberto, and Asymptomatic Carotid Surgery Trial Collaborative, Group

Subjects
Male, Time Factors, medicine.medical_treatment, Kaplan-Meier Estimate, Carotid endarterectomy, Aged, 80 and over, Carotid Stenosis, Endarterectomy, Carotid, Female, Humans, Incidence, Middle Aged, Primary Prevention, Stroke, Treatment Outcome, Stroke/epidemiology, law.invention, Randomized controlled trial, law, Aged, 80 and over, Endarterectomy, Carotid, endarterectomy, Carotid Stenosis/mortality, Incidence (epidemiology), Carotid*/mortality, General Medicine, Carotid Stenosis | Internal Carotid Artery | Endarterectomy, medicine.symptom, medicine.medical_specialty, Asymptomatic, Internal medicine, asymptomatic carotid artery stenosi, medicine, asymptomatic carotid artery stenosis, business.industry, Carotid Stenosis/complications, Stroke/prevention & control, Perioperative, medicine.disease, Surgery, Stenosis, Human medicine, business
Abstract

SummaryBackgroundIf carotid artery narrowing remains asymptomatic (ie, has caused no recent stroke or other neurological symptoms), successful carotid endarterectomy (CEA) reduces stroke incidence for some years. We assessed the long-term effects of successful CEA.MethodsBetween 1993 and 2003, 3120 asymptomatic patients from 126 centres in 30 countries were allocated equally, by blinded minimised randomisation, to immediate CEA (median delay 1 month, IQR 0·3–2·5) or to indefinite deferral of any carotid procedure, and were followed up until death or for a median among survivors of 9 years (IQR 6–11). The primary outcomes were perioperative mortality and morbidity (death or stroke within 30 days) and non-perioperative stroke. Kaplan-Meier percentages and logrank p values are from intention-to-treat analyses. This study is registered, number ISRCTN26156392.Findings1560 patients were allocated immediate CEA versus 1560 allocated deferral of any carotid procedure. The proportions operated on while still asymptomatic were 89·7% versus 4·8% at 1 year (and 92·1% vs 16·5% at 5 years). Perioperative risk of stroke or death within 30 days was 3·0% (95% CI 2·4–3·9; 26 non-disabling strokes plus 34 disabling or fatal perioperative events in 1979 CEAs). Excluding perioperative events and non-stroke mortality, stroke risks (immediate vs deferred CEA) were 4·1% versus 10·0% at 5 years (gain 5·9%, 95% CI 4·0–7·8) and 10·8% versus 16·9% at 10 years (gain 6·1%, 2·7–9·4); ratio of stroke incidence rates 0·54, 95% CI 0·43–0·68, p

Published
2010
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3. Wasseranalyse

Author

Hehner, O., Warington, R., Sutton, Smetham, Alfred, Hirt, L., Cohn, Certes, A., and Zerener, H.

Abstract

n/a

Published
1881

7. [News in neurology 2014]

Author

Tsetsou S, Ao, Rossetti, Michel P, Hirt L, Wider C, David Benninger, Kuntzer T, Nater B, Jf, Démonet, Schluep M, Ra, Du Pasquier, and Vingerhoets F

8. [Recent Advances in Neurology]

Author

Anichini A, Salvioni Chiabotti P, Bally J, Castro Jimenez M, Jf, Démonet, Di Virgilio G, Hirt L, Hottinger A, Kuntzer T, Michel P, Novy J, and Du Pasquier R

9. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients

Author

Aebischer, P., Schluep, M., Deglon, N., Joseph, J. M., Hirt, L., Heyd, B., Goddard, M., Hammang, J. P., Zurn, A. D., Kato, A. C., Regli, F., and Baetge, E. E.

Subjects
Amyotrophic Lateral Sclerosis/ drug therapy/ genetics/therapy, Cell Transplantation/methods, Spinal, Lumbar Vertebrae/surgery, Kidney/cytology/physiology, fluid/ therapeutic use, Injections, Genetic Vectors/chemistry/genetics, Drug Implants/administration & dosage/ chemistry, Gene Therapy/methods, Recombinant Proteins/administration & dosage/biosynthesis/therapeutic use, Cricetinae, Animals, Humans, Ciliary Neurotrophic Factor, Nerve Tissue Proteins/ administration & dosage/cerebrospinal
Abstract

Neuronal growth factors hold promise for providing therapeutic benefits in various neurological disorders. As a means of ensuring adequate central nervous system delivery of growth factors and minimizing significant adverse side effects associated with systemic delivery methods, we have developed an ex vivo gene therapy approach for protein delivery using encapsulated genetically modified xenogeneic cells. Ciliary neurotrophic factor (CNTF) has been shown in various rodent models to reduce the motor neuron cell death similar to that seen in amyotrophic lateral sclerosis (ALS). The initial trials focusing on the systemic administration of CNTF for ALS have been discontinued as a result of major side effects, thus preventing determination of the potential efficacy of the molecule. In order to deliver CNTF directly to the nervous system, we conducted a phase I study in which six ALS patients were implanted with polymer capsules containing genetically engineered baby hamster kidney cells releasing approximately 0.5 microgram of human CNTF per day in vitro. The CNTF-releasing implants were surgically placed within the lumbar intrathecal space. Nanogram levels of CNTF were measured within the patients' cerebrospinal fluid (CSF) for at least 17 weeks post-transplantation, whereas it was undetectable before implantation. Intrathecal delivery of CNTF was not associated with the limiting side effects observed with systemic delivery. These results demonstrate that neurotrophic factors can be continuously delivered within the CSF of humans by an ex vivo gene therapy approach, opening new avenues for the treatment of neurological diseases.

12. Régénération cellulaire neuronale post-ischémique : potentiel thérapeutique

Author

Badaut, J, Hirt, L, Regli, L, Villemure, J G, Bogousslavsky, J, and Magistretti, P J

Abstract

Différentes études ont mis en évidence une production continue de cellules progénitrices de neurones au cours de la vie adulte. Cette neurogenèse est observée dans certaines régions spécifiques du cerveau. Cette production de nouveaux neurones peut être stimulée soit physiologiquement comme l'apprentissage, soit après une lésion cérébrale. En effet, suite à une ischémie, il a été montré que la neurogenèse était augmentée. De plus, les nouveaux neurones semblent pouvoir remplacer les neurones lésés. Moyennant une meilleure compréhension de ce processus, ces résultats prometteurs permettent d’envisager l’utilisation thérapeutique de ces cellules progénitrices pour contrecarrer la perte neuronale, dans les différentes maladies neurodégénératives ou après une lésion du système nerveux central, d’origine ischémique ou traumatique

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