Sandercock P.,The 3 Co ordinating Center |
Lindley R.,University of Sydney |
Wardlaw J.,The 3 Co ordinating Center |
Dennis M.,The 3 Co ordinating Center |
And 25 more authors.
Trials | Year: 2011
Background: Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.Design: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.Results: The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.Conclusion: The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials.Trial registration: ISRCTN25765518. © 2011 Sandercock et al; licensee BioMed Central Ltd.
The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): A randomised controlled trial
Sandercock P.,University of Edinburgh |
Wardlaw J.M.,University of Edinburgh |
Lindley R.I.,University of Sydney |
Dennis M.,University of Edinburgh |
And 55 more authors.
The Lancet | Year: 2012
Background Thrombolysis is of net benefi t in patients with acute ischaemic stroke, who are younger than 80 years of age and are treated within 4.5 h of onset. The third International Stroke Trial (IST-3) sought to determine whether a wider range of patients might benefi t up to 6 h from stroke onset. Methods In this international, multicentre, randomised, open-treatment trial, patients were allocated to 0.9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) or to control. The primary analysis was of the proportion of patients alive and independent, as defi ned by an Oxford Handicap Score (OHS) of 0-2 at 6 months. The study is registered, ISRCTN25765518. Findings 3035 patients were enrolled by 156 hospitals in 12 countries. All of these patients were included in the analyses (1515 in the rt-PA group vs 1520 in the control group), of whom 1617 (53%) were older than 80 years of age. At 6 months, 554 (37%) patients in the rt-PA group versus 534 (35%) in the control group were alive and independent (OHS 0-2; adjusted odds ratio [OR] 1.13, 95% CI 0.95-1.35, p=0.181; a non-signifi cant absolute increase of 14/1000, 95% CI-20 to 48). An ordinal analysis showed a signifi cant shift in OHS scores; common OR 1.27 (95% CI 1.10-1.47, p=0.001). Fatal or non-fatal symptomatic intracranial haemorrhage within 7 days occurred in 104 (7%) patients in the rt-PA group versus 16 (1%) in the control group (adjusted OR 6.94, 95% CI 4.07-11.8; absolute excess 58/1000, 95% CI 44-72). More deaths occurred within 7 days in the rt-PA group (163 [11%]) than in the control group (107 [7%], adjusted OR 1.60, 95% CI 1.22-2.08, p=0.001; absolute increase 37/1000, 95% CI 17-57), but between 7 days and 6 months there were fewer deaths in the rt-PA group than in the control group, so that by 6 months, similar numbers, in total, had died (408 [27%] in the rt-PA group vs 407 [27%] in the control group). Interpretation For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefi t did not seem to be diminished in elderly patients. Funding UK Medical Research Council, Health Foundation UK, Stroke Association UK, Research Council of Norway, Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden, Swedish Heart Lung Fund, The Foundation of Marianne and Marcus Wallenberg, Polish Ministry of Science and Education, the Australian Heart Foundation, Australian National Health and Medical Research Council (NHMRC), Swiss National Research Foundation, Swiss Heart Foundation, Assessorato alla Sanita, Regione dell'Umbria, Italy, and Danube University.
Irlanda P.-B.,Instituto Nacional Of Cancerologia |
Silvia H.-T.,Hospital Infantil Of Mexico |
Silvia H.-T.,Metropolitan Autonomous University |
Kena Z.,Instituto Nacional Of Neurologia |
And 2 more authors.
AIP Conference Proceedings | Year: 2014
According to the World Cancer Report, by 2020, global incidence of cancer may increase by 50%, which means 15 million new cases. In 2000, malignant tumors were the cause of 12% of the almost 56 million deaths worldwide due to all causes[1-4]. 18 men and 19 women, with an average age of 53 ± 14 years with diagnosis of head and neck cancer were scanned using a 1.5-T MR imaging unit (Signa HDxt; GE Medical Systems). Echo-planar DW imaging was performed in the transverse plane before the contrast material injection. Three b values were applied: 40, 100, and 800 sec/mm2. Primary tumors and nodes were evaluated, with diameters greater than 43 ± 15mm. In our study, ADC data for b-values of 40 showed correlation for identification of malignancy in primary tumors, and in the case of nodes there is a tendency toward malignancy in sequences in which a b-value of 800 is used. © 2014 AIP Publishing LLC.
Systolic blood pressure and functional outcome in patients with acute stroke: A Mexican registry of acute cerebrovascular disease (RENAMEVASC) [Presión arterial sistólica y pronóstico funcional en pacientes con enfermedad vascular cerebral aguda: Registro Mexicano de enfermedad vascular cerebral]
Banos-Gonzalez M.,Hospital General Ticoman |
Cantu-Brito C.,Instituto Nacional Of Ciencias Medicas |
Chiquete E.,Instituto Nacional Of Ciencias Medicas |
Arauz A.,Instituto Nacional Of Neurologia |
And 4 more authors.
Archivos de Cardiologia de Mexico | Year: 2011
Objective: To analyze the association between the admission systolic blood pressure (SBP) and 30-day outcome in patients with acute cerebrovascular disease. Methods: The REgistro NAcional Mexicano de Enfermedad VAScular Cerebral (RENAMEVASC) is a hospital-based multicenter registry performed between November 2002 and October 2004. A total of 2000 patients with clinical syndromes of acute cerebrovascular disease confirmed by neuroimaging were registered. The modified Rankin scale was used for outcome stratification. Results: We analyzed 1721 patients who had registered their SBP: 78 (4.5%) had transient ischemic attack, 894 (51.9%) brain infarction, 534 (30.9%) intracerebral hemorrhage, 165 (9.6%) subarachnoid hemorrhage and 50 (2.9%) cerebral venous thrombosis. Among 1036 (60.2%) patients with the antecedent of hypertension, only 32.4% had regular treatment. The 30-day case fatality rate presented a J pattern with respect to SBP, so that the risk of death was highest in <100 mmHg (37.5%), decreased between 100 and 139, and reached gradually a new zenith in >220 mmHg (35.3%). The best functional outcome corresponded to patients who had SBP between 100 mmHg and 159 mmHg. In a Cox proportional hazards model, SBP <100 mmHg or >220 mmHg was an independent risk factor for 30-day mortality (RR: 1.52, IC 95%: 1.07 - 2.15), as well as the antecedent of hypertension (RR: 1.33, IC 95%: 1.06 - 1.65) and age >65 years (RR: 2.16, IC 95%: 1.74 - 2.67). Conclusion: Both hypotension and significant arterial hypertension at hospital admission are associated with an adverse outcome after acute cerebrovascular disease. Nevertheless, a good functional outcome can be attained in a wide range of SBP. © 2011 Instituto Nacional de Cardiología Ignacio Chávez.
Feria-Romero I.A.,Centro Medico Nacional Siglo XXI |
Alonso-Vanegas M.,Instituto Nacional Of Neurologia |
Rocha-Arrieta L.,Research Center Estudios Avanzados Sur |
Villeda-Hernandez J.,Instituto Nacional Of Neurologia |
And 5 more authors.
Revista Chilena de Neuro-Psiquiatria | Year: 2013
Epilepsy affects 1 and 2% of the worldwide population, while temporal lobe epilepsy (TLE) covers 40% of all epilepsy cases. Controversy in defining epilepsy as a neurodegenerative disease exists because, no there is enough evidence to show seizures and status epilepticus (SE) as cause for irreversible neuronal damage. Epileptogenic insult at the beginning of the disease produces an acute and delayed neuronal death, resulting in gliosis, but also triggers compensatory processes such as angiogenesis, cell proliferation and reorganization of extracellular matrix as receptors, channels and drug transporter proteins. In neurogenesis and axonal regrowth, the age of onset is crucial for the formation of abnormal neurons and aberrant circuits as a result of seizures; approximately 30% begin in the temporal lobe.These disturbances continue in parallel or sequentially during the course of epilepsy, which implies a great challenge in the search of new treatments.
Ochoa-Ruiz E.,National Autonomous University of Mexico |
Diaz-Ruiz R.,National Autonomous University of Mexico |
Hernandez-Vazquez A.D.J.,National Autonomous University of Mexico |
Ibarra-Gonzalez I.,National Autonomous University of Mexico |
And 9 more authors.
Molecular Genetics and Metabolism | Year: 2015
Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being amajor effect,whose responsiblemechanisms have not been thoroughly studied. Herewe show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases. Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders. © 2015 Elsevier Inc.
Gomez-Diaz B.,Instituto Nacional Of Rehabilitacion |
Rosas-Vargas H.,Hospital Of Pediatria |
Roque-Ramirez B.,Centro Medico Nacional |
Meza-Espinoza P.,Hospital Of Pediatria |
And 12 more authors.
Muscle and Nerve | Year: 2012
Introduction: The muscular dystrophies (MDs) result from perturbations in the myofibers. These alterations are induced in part by mechanical stress due to membrane cell fragility, disturbances in mechanotransduction pathways, muscle cell physiology, and metabolism. Methods: We analyzed 290 biopsies of patients with a clinical diagnosis of muscular dystrophy. Using immunofluorescence staining, we searched for primary and secondary deficiencies of 12 different proteins, including membrane, costamere, cytoskeletal, and nuclear proteins. In addition, we analyzed calpain-3 by immunoblot. Results: We identified 212 patients with varying degrees of protein deficiencies, including dystrophin, sarcoglycans, dysferlin, caveolin-3, calpain-3, emerin, and merosin. Moreover, 78 biopsies showed normal expression of all investigated muscle proteins. The frequency rates of protein deficiencies were as follows: 52.36% dystrophinopathies; 18.40% dysferlinopathies; 14.15% sarcoglycanopathies; 11.32% calpainopathies; 1.89% merosinopathies; 1.42% caveolinopathies; and 0.47% emerinopathies. Deficiencies in lamin A/C and telethonin were not detected. Conclusion: We have described the frequency of common muscular dystrophies in Mexico. © 2011 Wiley Periodicals, Inc.
Rodriguez-Zepeda J.M.,Centro Medico ABC |
Monzon-Falconi J.F.,Instituto Nacional Of Neurologia |
Ham-Mancilla O.,Centro Medico ABC |
Moreno-Jimenez S.,Centro Medico ABC |
And 2 more authors.
Revista Mexicana de Anestesiologia | Year: 2015
Background: The Arnold-Chiari malformation (ACM) is a group of congenital abnormalities of the hindbrain and the spinal cord and is characterized by herniation of the cerebellum, kinking of the medulla oblongata and hydrocephalus; the anesthetic management is complicated due to the anatomic and physiologic alterations. Case description: A 23 years old woman with Arnold-Chiari type II malformation, and perforated appendicitis. Conclusions: The present case demonstrates that patients with partially corrected ACM type II, restrictive lung disease due to scoliosis and perforated appendicitis delivery require an interdisciplinary team approach, diligent preparation, and skilled physicians. © 2015, Colegio Mexicano de Anestesiologia A.C. All Rights Reserved.
Orta D.S.-J.,Instituto Nacional Of Neurologia |
Del Castillo Calcaneo J.D.D.,Instituto Nacional Of Neurologia
Archivos de Neurociencias | Year: 2010
Since sleep is a vital component that is defined on the basis of individual behavior and electric cerebral activity, a relation between degenerative diseases such as Parkinson's and sleep disorders has been detected. Development. In this review, data concerning various sleep disorders and their relation to Parkinson's disease that have previously been published have been revised in this paper. The disorders that have been studied are insomnia, circadian rhythm alterations, sleep apnea, the restless legs syndrome and the disorder of periodic leg movements, the REM behavior disorder and the effects of anti-Parkinsonian treatment in sleep disorders. Conclusions. Sleep disorders are frequently found to be associated with Parkinson's disease, thus constituting an important comorbidity. They could forecast the short or long term appearance of Parkinson's disease. ©INNN, 2010.
Memory systems: Historical research, classification and current concepts. Second part: Long-term memory systems: Episodic memory, non-declarative memory systems and working memory [Sistemas de memoria: Reseña histórica, clasificación y conceptos actuales. Segunda parte: Sistemas de memoria de largo plazo: Memoria episódica, sistemas de memoria no declarativa y memoria de trabajo]
Carrillo-Mora P.,Instituto Nacional Of Neurologia
Salud Mental | Year: 2010
According to recent evidence, memory can be conceptualized as a series of subsystems working together to reach the same final goal. In the present time, most authors coincide in proposing a main division or long-term memory systems in mammals. This division separates memory in two categories: declarative and not declarative, often conceptualized also as explicit and implicit memories, respectively, although the latter terms are more appropriate to describe the role of consciousness during the development of codification and recovery tasks in regard to the information of each system. Declarative memory, as indicated by its name, includes a variety of memories implicating information that can be verbalized and effectively transmitted from person to person. This type of memory is conceptualized as conformed by two distinct memory sub-categories sometimes collaborating and coinciding in the use of memory. The first of these sub-categories is semantic memory, the one including the information about concepts and precise facts, and it is frequently defined as «general knowledge». It also makes reference to conceptual information lacking from the temporal-spatial frame (this issue is detailed in the first part of this paper). The second sub-category is episodic memory, which refers to the memory for personal experienced events, or the memory used for «what?, where?, and when?», in regard to the occurrence of a given personal event. Altogether, autonoesis (the conscious concept of a personally experienced event), subjective temporal consciousness (or subjective temporal frame about when a given event occurred), and self-consciousness are considered indispensable for the definition of episodic memory. In spite of these characteristics, there is yet controversy on whether this type of memory could be observed in animals. In this regard, some researchers have demonstrated that the processes needed to define episodic memory are effectively employed by non-human primates and rodents. In regard to the functional anatomy of episodic memory, an active role of the temporal lobe in the codification of some components of this memory is known from long time ago. Experimental studies employing hippocampal electro-physiological recordings have demonstrated that this region participates in two main components of episodic memory: i) the strong links of the subject with the environment or the spatial context, and ii) the temporal organization of the stored information. Some studies have clearly demonstrated the important participation of specific hippocampal cell areas (CA1 and CA3) for the resolution of behavioral tasks requiring episodic memory. However, clinical studies employing functional imaging have shown a considerable diversity of cortical areas as involved in the several processes of codification or recovery of episodic information, going from prefrontal medial and left ventrolateral regions to medial and lateral temporal regions, retrosplenial cortex, posterior cingulus posterior, and even the cerebellum. Non-declarative memory systems Non-declarative memory contains different categories: procedural memory, priming, associative learning (classic and operant conditioning) and non-associative learning (habituation and sensitization): a) Procedural memory refers to the storage and recovery of information on motor skills, or «know how to do» distinct tasks. Although this type of memory is considered as part of those memory systems often leading to unconscious learning, the relationship between procedural memory and consciousness is more complex. This is due in part to the fact that there is no evidence of a real association between the voluntary (conscious) desire of movement and the activation of motor brain areas. In addition, it has been demonstrated that movements consciously activated to start a given task may difficult the performance of the same task. Moreover, learning of motor skills exhibits a particular characteristic known as consolidation or off-line stabilization. This term refers to those motor skills exhibiting an improvement in performance during the interval of two practice sessions, meaning that the performance is improved if behavior is re-analyzed after an interval of rest typically occurring along the day or during sleep periods. This supports the theory that during sleep periods there is a recapitulation of events taking place during the day, thus favoring the strengthening of neuroplastic mechanisms involved in motor learning. b) Priming is a type of implicit memory not requiring any conscious recollection of previous experiences, and it shares some features with procedural and semantic memories. Similar to procedural memory, priming implies an increase of skills, but in this case, perceptual skills. It is also similar to semantic memory in terms of the involvement of cognitive representations of outdoor environment, and its representation is more cognitive than behavioral. The general characteristics of priming are: i) it is related with the perceptual identification of objects in general terms, including words or concepts; ii) its neuronal substrate is not depending on those brain regions needed for episodic or semantic memories; iii) it is developed early in life and its capacity remains stable all the time; iv) its activity is not related with consciousness and its function is not sufficient to recall a previous experience; v) it is relatively immune to the effects of drugs affecting the other memory systems; vi) its information is distributed in multiple representations of specific words and objects; and vii) the access to this representations is highly specific to each category of objects. Finally, among short-term memory systems, the concept of working memory proposed by Baddeley and Hitch is still accepted in our days, and is characterized by the transitory storage and administration of all kind of information useful for the achievement of a specific task. This system is based on three main components: i) a control system with limited attention capacity, also known as Executive Central Component; ii) the Phonologic Circuit, based on sound and language; and iii) the Visual-Spatial Scheme. The phonologic circuit is responsible for the transitory storage of language information based on sound and it is proponed to play an active role for learning of language. The Visual-Spatial Scheme is important for the visual-spatial representation of objects and their features, which in turn is relevant for the integration of concepts. The Executive Central Component is in charge of controlling the attention and the access to the other two subsidiary components. The knowledge on how the memory systems are functioning is and will remain in constant expansion, given the obvious contribution of recent studies on molecular biology and functional neuroimaging.