Search

La enfermedad periodontal y la enfermedad cerebrovascular son procesos muy prevalentes en personas de avanzada edad. Diversos estudios han demostrado una asociacion entre ambos, aunque existen diferencias metodologicas que dificultan la interpretacion de los resultados. El objetivo de este articulo es realizar una revision critica de los estudios publicados sobre esta asociacion. Se incluyen 11 estudios prospectivos y 11 estudios retrospectivos, y se analizan las distintas variables metodologicas (poblacion de estudio, diagnostico de enfermedad periodontal, definicion de enfermedad cerebrovascular, variables ajustadas, seguimiento y odds ratio/riesgo relativo). Ademas, se analizan diferentes mecanismos patogenicos que pueden influir en la progresion e interrelacion entre ambos procesos.

To study the association of previously unknown high blood pressure (HBP) during the acute phase of stroke (new-onset hypertension) with the inflammatory response and clinical outcome.We classified 844 patients with hemispheric ischemic stroke into three groups according to history of hypertension and presence of HBP within the first 24 hours after symptom onset: Group I (n = 412), normotensive patients; Group II (n = 265), chronic hypertensive patients; and Group III (n = 167), new-onset hypertensive patients. Interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and metalloproteinase 9 (MMP-9) were measured in blood samples obtained on admission. The influence of new-onset HBP and markers of inflammation on poor neurologic outcome at 3 months was evaluated by logistic regression analysis.New-onset HBP was found in 19.9% of patients. Patients in this group had higher plasma concentrations of IL-6, TNF-alpha, ICAM-1, VCAM-1, and MMP-9 than the other two groups. New-onset HBP was associated with poor outcome at 3 months (odds ratio [OR] 2.10; 95% CI 1.54 to 3.52; p0.0001) after adjustment for other prognostic factors. However, when markers of inflammation were included in the model, IL-6 (OR 1.01; 95% CI 1.00 to 1.03; p = 0.020) and MMP-9 (OR 1.01; 95% CI 1.00 to 1.01; p0.0001), but not new-onset HBP, were independently associated with poor neurologic outcome.New-onset high blood pressure in acute ischemic stroke, but not chronic hypertension, is associated with an inflammatory response and poor neurologic outcome.

Background and Purpose— Iron overload has been associated with greater oxidative stress and brain injury in experimental cerebral ischemia and reperfusion. This study investigates whether high serum ferritin levels, as an index of increased cellular iron stores, are associated with poor outcome, hemorrhagic transformation, and brain edema after treatment with tissue plasminogen activator in patients with acute ischemic stroke. Methods— A total of 134 consecutive patients treated with intravenous tissue plasminogen activator were prospectively studied in four centers. Serum ferritin levels were determined at baseline, 24 and 72 hours after treatment. Cranial computed tomography was performed on admission and at 24 to 36 hours after tissue plasminogen activator infusion. Stroke severity and outcome were evaluated by using the National Institute of Health Stroke Scale and the modified Rankin Scale. Results— Computed tomography showed hemorrhagic transformation in 27 patients (hemorrhagic infarction in 15 and parenchymal hematoma in 12; symptomatic in four) and brain swelling with midline shift in 15. Poor outcome (modified Rankin Scale >2) at 90 days was observed in 54.5% of patients. Ferritin levels at baseline were higher in patients with poor outcome at 90 days (median [quartiles], 165 [98,307] versus 17 [12,37] ng/mL; P P =0.006), symptomatic hemorrhagic transformation ( P =0.008), and severe brain edema ( P Conclusions— Increased body iron stores are associated with poor outcome, symptomatic hemorrhagic transformation, and severe edema in patients treated with tissue plasminogen activator after ischemic stroke. These findings suggest that iron overload may offset the beneficial effect of thrombolytic therapies.

Chronic impairment of forelimb and digit movement is a common problem after stroke that is resistant to therapy. Although in the last years some studies have been performed to increase the efficacy of rehabilitative experience and training, the pharmacological approaches in this context remain poorly developed. We decided to study the effect of a chronic treatment with CDP-choline, a safe and well-tolerated drug that is known to stabilize membranes, on functional outcome and neuromorphological changes after stroke. To assess the functional recovery we have performed the staircase reaching test and the elevated body swing test (EBST), for studying sensorimotor integration and asymmetrical motor function respectively. The treatment with CDP-choline, initiated 24 h after the middle cerebral artery occlusion (MCAO) and maintained during 28 days, improved the functional outcome in both the staircase test (MCAO+CDP=87.0+/-6.6% pellets eaten vs. MCAO+SAL=40.0+/-4.5%; p

Although the management of stroke has improved remarkably over the last decade due mainly to the advent of thrombolysis, most neuroprotective agents, although successful in animal studies, have failed in humans. Our increasing knowledge concerning the ischemic cascade is leading to a considerable development of pharmacological tools suggesting that each step of this cascade might be a target for cytoprotection. Glutamate has long been recognized to play key roles in the pathophysiology of ischemia. However, although some trials are still ongoing, the results from several completed trials with drugs interfering with the glutamatergic pathway have been disappointing. Regarding the inhibition of glutamate release as a possible target for cytoprotection, it might be afforded either by decreasing glutamate efflux or by increasing glutamate uptake. In this context, it has been shown that glutamate transport is the primary and only mechanism for maintaining extracellular glutamate concentrations below excitotoxic levels. This transport is executed by the five high-affinity, sodium-dependent plasma membrane glutamate transporters. Among them, the transporter EAAT2 is responsible for up to 90% of all glutamate transport. We will discuss the effect of different neuroprotective tools (membrane stabilizers or endogenous neuroprotection) affecting glutamate efflux and/or expression of EAAT2. We will also describe the finding of a novel polymorphism in the EAAT2 promoter region which could be responsible for differences in both gene function and regulation under pathological conditions such as cerebral ischemia, and which might well account for the failure of glutamate antagonists in the clinical practice. These results may possess important therapeutic implications in the management of patients at risk of ischemic events, since it has been demonstrated that those patients with progressing stroke have higher plasma concentrations of glutamate which remain elevated up to 24 h when compared to the levels in patients without neurological deterioration.

Vascular damage occurring after cerebral ischemia may lead to a worse outcome in patients with ischemic stroke, as it facilitates edema formation and hemorrhagic transformation. There are several phases in the development of vascular injury (acute, subacute and chronic) and different mediators act in each one. Therapeutic options to avoid vascular injury must be focused on acting in each phase. However, even though experimental studies have demonstrated the benefit of therapeutic interventions both in the acute and chronic phases of cerebral ischemia, only the chronic phase offers a therapeutic window sufficiently wide enough to provide vascular protection in clinical practice. Several drugs including erythropoietin and HMG-CoA reductase inhibitors (statins), antihypertensive (angiotensin modulators), antibiotics (minocycline) and antihyperglycemic drugs (thiazolidinediones) have been proved to provide vascular protection in patients with ischemic stroke. Anti-inflammatory, antioxidant, and antiapoptotic actions are responsible for the vascular protective effect related to these drugs.

Stroke is the second to third leading cause of death and the main cause of severe, long-term disability in adults. However, treatment is almost reduced to fibrinolysis, a therapy useful in a low percentage of patients. Given that the immediate treatment for stroke is often unfeasible in the clinical setting, the need for new therapy strategies is imperative. After stroke, the remaining impairment in functions essential for routine activities, such as movement programming and execution, sensorimotor integration, language and other cognitive functions have a deep and life-long impact on the quality of life. An interesting point is that a slow but consistent recovery can be observed in the clinical practice over a period of weeks and months. Whereas the recovery in the first few days likely results from edema resolution and/or from reperfusion of the ischemic penumbra, a large part of the recovery afterwards is due mainly to brain plasticity, by which some regions of the brain assume the functions previously performed by the damaged areas. Neurogenesis and angiogenesis are other possible mechanisms of recovery after stroke. An understanding of the mechanisms underlying functional recovery may shed light on strategies for neurorepair, an alternative with a wide therapeutic window when compared with neuroprotective strategies.

Ischemic penumbra defines the existence of tissue at risk of infarction and which is, hence, potentially salvageable and the target for current stroke reperfusion and neuroprotective therapies. Penumbral tissue evolves toward irreversibly damaged tissue at different rates in individual stroke patients yielding different therapeutic windows depending on the individual duration of risk of infarction of this tissue. An accurate identification of the penumbra is then necessary in order to individualize the window of opportunity for therapeutic interventions. Imaging techniques, although helpful, may not give the most accurate information as to the existence of penumbra given that the threshold for identification of penumbra varies depending on the technique used. A better identification of the true penumbral tissue might be based on the cascade of molecular events that are responsible for the evolution of the penumbra toward infarcted tissue. Multiple penumbras can be defined in molecular terms taking into account which vessel is occluded, the time of evolution of the ischemia, the degree of the ischemia, and the sensitivity to ischemia of the different cells. Future studies are necessary to clarify whether the enhancement of cytoprotective mechanisms, and/or the block of cytotoxic mechanisms confirming the existence of penumbra at different times of ischemic evolution, are effective neuroprotective strategies.

Ischemic preconditioning involves a brief exposure to ischemia in order to develop a tolerance to injurious effects of prolonged ischemia. The molecular mechanisms of neuroprotection that lead to ischemic tolerance are not yet completely understood. However, it seems that two distinct phases are involved. Firstly, a cellular defense function against ischemia may be developed by the mechanisms inherent to neurons such as posttranslational modification of proteins or expression of new proteins via a signal transduction system to the nucleus. Secondly, a stress response and synthesis of stress proteins (heat shock proteins) may be activated. These mechanisms are mediated by chaperones. The objective of ischemic preconditioning research is to identify the underlying endogenous protective cellular receptors and signaling cascades, with the long-term goal of allowing therapeutic augmentation of the endogenous protective mechanisms in cerebral ischemia and possibly development of new neuroprotective strategies for ischemic stroke treatment.

It remains unclear why some individuals are susceptible to excitotoxicity after stroke. A possible explanation is impaired glutamate uptake. We have found a highly prevalent polymorphism in the promoter of the glutamate transporter EAAT2 gene that abolishes a putative regulatory site for activator protein–2 (AP-2) and creates a new consensus binding site for the repressor transcription factor GC-binding factor 2 (GCF2). The mutant genotype is associated with increased plasma glutamate concentrations and with a higher frequency of early neurological worsening in human stroke. After transfection into astrocytes, the mutant promoter was not activated by AP-2 and was effectively repressed by GCF2, and its activity in the presence of GCF2 was reduced when compared with the AP-2–cotransfected wild-type promoter. We also show that GCF2 is expressed in ischemic rat brain, suggesting that decreased glutamate uptake occurs in individuals carrying the mutation after stroke. These findings may explain individual susceptibility to excitotoxic damage after stroke as well as the failure of glutamate antagonists in those patients without this polymorphism.

Depression is associated with poor functional recovery inacute ischemic stroke. Though some factors associated todepression at few months are known, little is knownabout depression in acute phase of stroke and its relatedfactors. The objective of this research is to study the fre-quency of depression in acute phase of stroke, as well aswhat clinical and psychological variables are related withits development and evolution.

Se registra y discute la distribución ecológica de 130 especies de macromicetos (9 Ascomycotina, 4 Tremellales 30 Aphyllophorales, 5 Boletales, 70 Agaricales y 12 Gasteromycetes) del cerro El Zamorano, situado entre Querétaro y Guanajuato. Solamente se conocían 16 especies de hongos de dicho cerro. La vegetación del cerro la constituyen bosques de Quercus, de Abies religiosa y de Abies religiosa con Quercus. Se identificaron 55 especies de hongos comestibles, pero solamente Clavulina amethystina y Lycoperdon perlatum se usan como tales en la región. Interesante fue encontrar especies neotropicales en esta región, como Daldinia concentrica, Hexagonia hydnoides, Hydnopolyporus fimbriatus, Hypoxylon thoursianum, Pycnoporus sanguineus y Schizophyllum commune lo que indica cierta influencia tropical en el cerro.

The clinical profile of hepatotoxicity induced by tuberculosis drugs varies and the re-introduction of therapy for patients who developed this condition is controversial.5 pediatric cases treated throughout a period of 10 years in the Pediatric Department of Hipolito Unanue National Hospital are presented.2 individuals showed an asymptomatic increase of transaminases, 2 individuals had hepatitis, and 1 individual had acute liver failure. Most patients were female school students. Malnutrition and therapy continuation once the hepatic damage was started were found to be the risk factors.A staged reintroduction scheme for these agents after recovery from hepatitis is proposed.

The fear of incompatibility issues between legacy IPv4 systems and new IPv6 implementations can delay the migration towards a full IPv6 native Internet. Network engineers need to ensure that heterogeneous IPv6 devices behaves consistently to the IPv6 specifications and correctly enterprise in a multi-vendor environment. This paper analyzes IPv6 conformance testing, a set of rigorous test methodologies that allows to throughout verify the quality of IPv6 devices during their entire life cycle, and can give confidence to the customers. We analyze the TAHI IPv6 conformance and interoperability test suite and present our conformance test results for the latest versions of IPv6 host implementations.

Background and Purpose— Space-occupying brain edema is a life-threatening complication in patients with large hemispheric stroke. The aim of the study was to determine whether molecular markers of endothelial damage may help to predict secondary brain edema and, secondly, to identify patients who could benefit from aggressive therapies such as decompressive hemicraniectomy or hypothermia. Methods— We studied 40 consecutive patients with malignant middle cerebral artery (MCA) infarction and 35 controls with massive MCA infarctions Results— Mean time from stroke onset to blood sampling was 6.3±4.8 in m-MCA and 7.7±6.0 hours in the control group ( P =0.63). Baseline characteristics were comparable in both groups. c-Fn and MMP-9 levels were significantly higher in patients with m-MCA than in controls (all P 16.6 μg/mL had the highest sensitivity (90%), specificity (100%), and negative and positive predictive values (89% and 100%, respectively) for the prediction of m-MCA infarction. Conclusions— A plasma c-Fn concentration >16.6 μg/mL at admission is associated with the development of m-MCA infarction with high sensitivity and specificity, suggesting that c-Fn might be useful in therapeutic decision making.

Stroke triggers an inflammatory cascade which contributes to a delayed cerebral damage, thus implying that antiinflammmatory strategies might be useful in the treatment of acute ischaemic stroke. Since two unrelated peroxisome proliferator-activated receptor-γ (PPARγ) agonists, the thiazolidinedione rosiglitazone (RSG) and the cyclopentenone prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), have been shown to possess antiinflammatory properties, we have tested their neuroprotective effects in experimental stroke. Rosiglitazone or 15d-PGJ2 were administered to rats 10 mins or 2 h after permanent middle cerebral artery occlusion (MCAO). Stroke outcome was evaluated by determination of infarct volume and assesment of neurological scores. Brains were collected for protein expression, gene array analyses and gene shift assays. Our results show that both compounds decrease MCAO-induced infarct size and improve neurological scores. At late times, the two compounds converge in the inhibition of MCAO-induced brain expression of inducible NO synthase and the matrix metalloproteinase 9. Interestingly, at early times, complementary DNA microarrays and gene shift assays show that different mechanisms are recruited. Analysis of early nuclear p65 and late cytosolic IκBα protein levels shows that both compounds inhibit nuclear factor-κB signalling, although at different levels. All these results suggest both PPARγ-dependent and independent pathways, and might be useful to design both therapeutic strategies and prognostic markers for stroke.

Lacunar infarction has long been considered to be associated with good prognosis, however a significant percentage of these patients remain functionally dependent. In this study we sought to investigate the factors associated with poor outcome in patients with lacunar infarction. Subjects and Methods: We have performed a secondary study in 113 patients with lacunar infarctions admitted within the first 24 h of symptom onset (mean age 70 years, 57.5% men). Blood pressure, body temperature, serum glucose levels, neurotransmitters and pro-inflammatory markers were measured at admission and during the first 72 h. Stroke severity was assessed by the Canadian Stroke Scale (CSS). Neuroimaging evaluation was performed at admission and between days 4 and 7. Poor functional outcome was considered as a Barthel index Results: 36 patients (31.9%) had poor outcome. Older age (p = 0.009), history of hypertension (p = 0.005), higher body temperature (p < 0.0001), systolic blood pressure (SBP) (p = 0.010), serum glucose (p = 0.002) and interleukin-6 (IL-6) (p < 0.0001) levels, as well as lower CSS score at admission (p < 0.0001) were all predictive factors of poor outcome in bivariate analyses. SBP at admission (OR 2.07, CI 95% 1.04–3.28, p = 0.015) was the only clinical predictor on multivariate analysis. When the logistic model was further adjusted for biomarkers of inflammation and excitotoxicity, IL-6 levels (OR 1.09, CI 95% 1.01–1.26, p = 0.003), but not SBP, was independently associated with poor outcome. This association persisted even after adjusting for potential predictors recorded during the first 72 h of hospitalization. Conclusion: High SBP and IL-6 levels on admission may predict poor outcome in patients with lacunar infarction.

Background and Purpose— The 15-deoxy Δ prostaglandin J 2 (15-dPGJ 2 ) is an anti-inflammatory prostaglandin that has been proposed to be the endogenous ligand of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor that can exert potent anti-inflammatory actions by repressing inflammatory genes when activated. It has been suggested that 15-dPGJ 2 could be beneficial in neurological disorders in which inflammation contributes to cell death such as stroke. Methods— We investigated the relationship between plasma levels of 15-dPGJ 2 and early neurological deterioration (END), infarct volume, and neurologic outcome in 552 patients with an acute stroke admitted within 24 hours after symptoms onset. Results— Median [quartiles] plasma 15-dPGJ 2 levels on admission were significantly higher in patients than in controls (60.5 [11.2 to 109.4] versus 5.0 [3.8 to 7.2] pg/mL; P P 2 were 0.95 (95% CI, 0.94 to 0.97) and 0.97 (95% CI, 0.96 to 0.98), respectively. In a generalized linear model, by 1 U increase in 15-dPGJ 2 , there was a reduction of 0.47 mL (95% CI, 0.32 to 0.63) in the mean estimated infarct volume. Conclusions— Increased plasma 15-dPGJ 2 concentration is associated with good early and late neurological outcome and smaller infarct volume. These findings suggest a neuroprotective effect of 15-dPGJ 2 in atherothrombotic ischemic stroke.

A short ischemic event (ischemic preconditioning (IPC)) can result in subsequent resistance to severe ischemic injury (ischemic tolerance (IT)). The expression and neuroprotective role of tumor necrosis factor (TNF- α) have been described in models of IPC and we have showed the participation of its processing enzyme, the TNF- α convertase enzyme (TACE) in this process. We have now decided to explore the expression and localization of TNF receptors (TNFR) as well as other signalling mechanisms involved in IT. A period of 10 mins of temporary middle cerebral artery occlusion (tMCAO) was used for focal IPC. To evaluate the ability of IPC to produce IT, permanent MCAO was performed 48 hours after IPC. Ischemic preconditioning produced a reduction in infarct volume, as we showed previously. Ischemic preconditioning caused upregulation of neuronal TNFR1 that was reduced by the selective TACE inhibitor BB1101. Intracerebral administration of TNFR1 antisense oligodeoxynucleotide, which caused a reduction in TNFR1 expression, inhibited the IPC-induced protective effect, showing that TNFR1 upregulation is implicated in IT. Moreover, treatment with BB1101, TNFR1 antisense and lactacystin—a specific proteasome inhibitor—blocked IPC-induced NF- κB. Immunohistochemical studies showed the expression of TACE and TNFR1 in neurons. In summary, these data show that IPC produces neuronal upregulation of TACE and TNFR1, and that the pathway TACE/TNF- α/TNFR1/NF- κB is involved in IT.

Background and Purpose— To investigate whether molecular markers of inflammation and endothelial injury are associated with early growth of intracerebral hemorrhage (ICH). Methods— In a multicenter prospective study, we determined concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and cellular fibronectin (c-Fn) in blood samples obtained on admission from 183 patients with primary hemispheric ICH of 33% between the 2 CT examinations for ICH with a baseline volume 10% for ICH ≥20 mL. Clinical, radiological, and biochemical predictive factors of ICH enlargement were analyzed by logistic regression analysis. Results— Fifty-four (29.5%) patients showed a relevant early growth of ICH. High leukocyte count and fibrinogen levels, low platelet count, and intraventricular bleeding were associated with early ICH growth in bivariate analyses. Plasma concentrations of IL-6 (median [quartiles]: 19.6 [13.6; 29.9] versus 15.9 [11.5; 19.8] pg/mL), TNF-α (13.5 [8.4; 30.5] versus 8.7 [4.7; 13.5] pg/mL), MMP-9 (153.3 [117.7; 204.7] versus 70.6 [47.8; 103.8] ng/mL), and c-Fn (8.8 [6.2; 12.5] versus 2.8 [1.6; 4.2] μg/mL) were significantly higher in patients with early growth of ICH (all P 6 μg/mL (OR, 92; 95%CI, 22 to 381; P 24 pg/mL (OR, 16; 95%CI, 2.3 to 119; P =0.005) were independently associated with ICH enlargement in the logistic regression analysis. Conclusions— Molecular signatures of vascular injury and inflammatory markers in the early acute phase of ICH are associated with subsequent enlargement of the hematoma.

Chile has implemented a stable funding policy to access lowincomehousing for more than two decades. Thus, due to itsachievements reducing the housing deficit the country isconsidered to be a reference. But, which is the cost? Houseshave been built but the city has not. Design and constructionstandards are quite poor and low-income housing is placed inghettos located in the outskirts of the city.Considering these and other deficiencies, the Government hasrestructured the country’s low-income housing policy to driveinnovating projects of renewal and densification of urbanneighborhoods. Responding to this initiative the School ofArchitecture of the Universidad Católica de Chile, hasdeveloped projects that intend to answer the followingqueries: Which is the city we want? What kind of housing isneeded? How does the beneficiary get involved in theproduction process?The pilot project «Renovación de las Poblaciones mediante laRadicación de Allegados» (Urban Renewal through Settlementof Guest Families) is the implementation of a several yearsacademic experience in the subject. The strategy consists inthe construction of a new housing unit for the guest familywithin the lot where they already live in poor conditions,without the need for a new lot they would have to buysomewhere else. Therefore, they can invest the total amount ofthe housing subsidy using the exiting infrastructure, and makeit possible for the residents to stay in their neighborhoods andreinforce the social network.In addition, this project caused a significant change in thebuilding codes and regulations that allow more flexible designrequirements for the second housing unit built in an existinglot. This change is a breakthrough that will benefit all thefuture projects aiming to increase the neighborhood’s density. Chile, después de 20 años de implementación de una políticafinanciera estable de acceso a la vivienda, es considerado unreferente por los logros alcanzados en la disminución deldéficit habitacional. Pero, ¿a qué costo? Se ha hechovivienda pero no se ha hecho ciudad, la calidad del diseño yde la construcción es deficiente, y la localización esperiférica y segregada.Considerando estos y otros defectos, el Gobierno hareestructurado la política habitacional para impulsarproyectos innovadores de renovación y densificación enáreas urbanas. Haciéndose eco de estos nuevos aires, laFacultad de Arquitectura de la Universidad Católica hadesarrollado proyectos que intentan dar respuesta a lassiguientes interrogantes: ¿Qué ciudad queremos? ¿Quévivienda necesitamos? ¿Cómo se incorpora al beneficiario enel proceso?El proyecto piloto “Renovación de las Poblaciones mediantela Radicación de Allegados” es la validación práctica deaños de experiencia académica en el tema. La estrategiaconsiste en la construcción de una nueva vivienda para losallegados en los lotes donde habitan precariamente, sinnecesidad de adquirir terreno nuevo. Esto permite destinar elmonto total del subsidio a la vivienda aprovechando lasinfraestructuras existentes, y mantener a la población en suscomunas de origen fortaleciendo las redes sociales.Este proyecto generó además un cambio importante en lanormativa que flexibiliza las exigencias de diseño parasegundas viviendas en lotes existentes, lo que supone un granavance del que se podrán beneficiar todos los proyectos dedensificación en poblaciones en el futuro.

Background and Purpose— Elevated plasma levels of cellular fibronectin (c-Fn) reflect vascular damage, so c-Fn might be a marker of secondary bleeding risk in cerebral ischemia. We investigated whether high plasma levels of c-Fn were associated with hemorrhagic transformation (HT) after treatment with tissue plasminogen activator (tPA) in patients with acute stroke. Methods— Eighty-seven patients (mean age: 67±12) received tPA after the ECASS II criteria (mean time to infusion: 160±46 minutes; median NIHSS: 12). HT and hypodensity volume were studied on computed tomography (CT) performed 24 to 36 hours after treatment. HT was classified according to the ECASS II definitions. c-Fn and matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA in blood samples obtained before treatment and in 30 healthy subjects. Results— HT was found in 26 patients (30%); 15 patients had hemorrhagic infarction type 1 (HI-1), 7 had HI-2, and 4 had parenchymal hemorrhage (PH). Median c-Fn concentrations were 1.3, 1.7, 4.2, 5.4, and 7.3 μg/mL in controls, non-HT, HI-1, HI-2, and PH groups, respectively ( P P P =0.002). Similar results were obtained in the 71 patients treated within 3 hours. Conclusions— High plasma c-Fn levels are significantly associated with subsequent HT in stroke patients treated with tPA, so plasma c-Fn determinations might be useful in clinical practice to improve the risk/benefit ratio of thrombolytic treatment.

Chile has implemented a stable funding policy to access lowincomehousing for more than two decades. Thus, due to itsachievements reducing the housing deficit the country isconsidered to be a reference. But, which is the cost? Houseshave been built but the city has not. Design and constructionstandards are quite poor and low-income housing is placed inghettos located in the outskirts of the city.Considering these and other deficiencies, the Government hasrestructured the country’s low-income housing policy to driveinnovating projects of renewal and densification of urbanneighborhoods. Responding to this initiative the School ofArchitecture of the Universidad Católica de Chile, hasdeveloped projects that intend to answer the followingqueries: Which is the city we want? What kind of housing isneeded? How does the beneficiary get involved in theproduction process?The pilot project «Renovación de las Poblaciones mediante laRadicación de Allegados» (Urban Renewal through Settlementof Guest Families) is the implementation of a several yearsacademic experience in the subject. The strategy consists inthe construction of a new housing unit for the guest familywithin the lot where they already live in poor conditions,without the need for a new lot they would have to buysomewhere else. Therefore, they can invest the total amount ofthe housing subsidy using the exiting infrastructure, and makeit possible for the residents to stay in their neighborhoods andreinforce the social network.In addition, this project caused a significant change in thebuilding codes and regulations that allow more flexible designrequirements for the second housing unit built in an existinglot. This change is a breakthrough that will benefit all thefuture projects aiming to increase the neighborhood’s density., Chile, después de 20 años de implementación de una políticafinanciera estable de acceso a la vivienda, es considerado unreferente por los logros alcanzados en la disminución deldéficit habitacional. Pero, ¿a qué costo? Se ha hechovivienda pero no se ha hecho ciudad, la calidad del diseño yde la construcción es deficiente, y la localización esperiférica y segregada.Considerando estos y otros defectos, el Gobierno hareestructurado la política habitacional para impulsarproyectos innovadores de renovación y densificación enáreas urbanas. Haciéndose eco de estos nuevos aires, laFacultad de Arquitectura de la Universidad Católica hadesarrollado proyectos que intentan dar respuesta a lassiguientes interrogantes: ¿Qué ciudad queremos? ¿Quévivienda necesitamos? ¿Cómo se incorpora al beneficiario enel proceso?El proyecto piloto “Renovación de las Poblaciones mediantela Radicación de Allegados” es la validación práctica deaños de experiencia académica en el tema. La estrategiaconsiste en la construcción de una nueva vivienda para losallegados en los lotes donde habitan precariamente, sinnecesidad de adquirir terreno nuevo. Esto permite destinar elmonto total del subsidio a la vivienda aprovechando lasinfraestructuras existentes, y mantener a la población en suscomunas de origen fortaleciendo las redes sociales.Este proyecto generó además un cambio importante en lanormativa que flexibiliza las exigencias de diseño parasegundas viviendas en lotes existentes, lo que supone un granavance del que se podrán beneficiar todos los proyectos dedensificación en poblaciones en el futuro.

The study of molecular markers associated with stroke has proved to be of considerable utility. We review the main biochemical changes of neurotoxicity and of inflammation and their usefulness as markers associated with early signs of ischaemia in the neuroimage, with early neurological deterioration, with the volume of the infarct, with haemorrhagic transformation, with the efficacy of thrombolytic treatment and with malignant ischaemic syndrome. Raised plasma concentrations of interleukin-6 (IL-6) are a powerful predictor of early neurological deterioration and the more important molecular marker associated with final volume of infarct. Levels of matrix metalloproteinases-9 (MMP-9) have a significant relationship with the efficacy of thrombolytic treatment and with the incidence and seriousness of haemorrhagic complications.

Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF-alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p0.0001) and IL-6 levels were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p0.0001) in patients with prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF-alpha in the presence of reduced concentrations of IL-6.

In patients with acute exacerbations of chronic obstructive pulmonary disease (COPD), noninvasive ventilatory support (NPPV) with bilevel positive airway pressure (BiPAP) may improve clinical and physiological parameters. The present study used a randomized, prospective design to evaluate the possible benefits of NPPV plus standard therapy versus standard therapy alone in patients admitted with acute hypercapnic respiratory failure in a respiratory unit of a tertiary hospital.Forty-one patients were included in the study. Of them, 20 were randomly allocated to receive NPPV with a standard mask connected to a BiPAP ventilatory assist device (Respironics Inc, Murrysville, PA) and 21 to standard therapy. Both groups had similar characteristics upon their admission in the hospital.The use of noninvasive ventilation significantly reduced the respiratory rates and improved the conscious level within the first 2 h (p0.001). There were significant differences in PaCO2 and pH (p0.05) at 6 h of treatment. The need for intubation was 5% in the NPPV group vs 14% in the control group. The length of hospital stay was significantly shorter in the NPPV group (7 vs 10 days; p0.01). Nasal NPPV was well tolerated and complications were uncommon and mild.Early use of noninvasive ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease leads to a more rapid improvement of physiological variables. Moreover, it is possible to apply this treatment in a general respiratory ward.

Aspirin may reduce ischemic brain injury. The aim of this study was to explore the effect of aspirin on glutamate release after acute stroke. We studied 238 patients with a first episode of hemispheric ischemic stroke of less than 24 h duration. Early neurological deterioration was diagnosed when the Canadian Stroke Scale dropped 1 or more points between admission and 48 h. Glutamate was determined on cerebrospinal fluid (CSF) samples obtained at admission. Sixty-three patients were undergoing treatment with 75-500 mg/day of aspirin at the time of stroke onset. CSF glutamate concentrations were higher in the group of patients not taking aspirin (8.9+/-5.2 vs. 4.9+/-3.1 microM/l, P< 0.0001). Aspirin treatment at stroke onset had a 97% risk reduction of early neurological deterioration, and this effect remained unchanged after a further adjustment for glutamate concentrations. These findings suggest that low doses of aspirin may be useful in the management of patients with cerebral ischemia, not only for its antithrombotic properties, but also by direct neuroprotective effects.

Background - Mechanisms involved in stroke progression are incompletely understood. Ischemic brain injury is characterized by acute local inflammatory response mediated by cytokines. Anti-inflammatory cytokines act in a feedback loop to inhibit continued proinflammatory cytokine production. We assessed the implication of interleukin (IL)-10 and IL-4 in deteriorating ischemic stroke. Methods - Two hundred thirty-one patients with ischemic stroke within the first 24 hours from onset were included. Neurological worsening was defined when the Canadian Stroke Scale score fell at least 1 point during the first 48 hours after admission. Anti-inflammatory cytokines were determined in plasma obtained on admission. Results - Eighty-three patients (35.9%) worsened within the first 48 hours after stroke onset. Significantly lower concentrations of IL-10 were found in patients with neurological worsening (P

Whether the risk of symptomatic hemorrhagic transformation (SHT) of cerebral infarction associated with the use of tissue plasminogen activator (t-PA) is higher in clinical practice than in clinical trials is unknown. The aim of this study was to analyze the safety profile and clinical outcome of patients with acute cerebral ischemia who received open treatment with t-PA in Spanish hospitals.This prospective and observational study included 155 consecutive patients with an ischemic stroke treated within 3 hours from the onset of symptoms, or within 6 hours in the absence of early signs of large cerebral infarction on CT. Intravenous t-PA was administered at 0.9 mg/kg (10% as bolus) during a 60 minutes infusion. Neurological worsening within 24-36 hours was evaluated by the NIH stroke scale (NIHSS). Primary safety and outcome variables were SHT on CT performed at 24-36 hours, mortality and independence at 90 days. Patients were treated by neurologists with expertise in acute stroke, and stroke monitoring was performed in acute stroke units.Baseline median NIHSS was 16, and mean time from stroke onset to treatment was 163 minutes. SHT was found in 12 patients (7.7%; 95% CI, 4.0-13.1), and it was fatal in 7 (4.5%, 95% CI, 1.8-9.1). Overall mortality at 90 days was 16.8% (95% CI, 11.2-23.6). At 24 hours, 48% (95% CI, 39.7-55.9) of patients had improved= 4 points in the NIHSS, and 29% (95 % CI, 22.0-36.8) showed a= 10 points improvement or total recovery. At 3 months, 56% (95% CI, 47.9-64.1) of patients were independent.In Spanish hospitals with stroke units or stroke teams, the use in the clinical practice of intravenous t-PA by experienced neurologists is safe, and it is associated with a favourable outcome similar to that observed in clinical trials.

Background and Purpose— Matrix metalloproteinase-9 (MMP-9) activity has been associated with hemorrhagic transformation (HT) in experimental models of cerebral ischemia. Our aim was to investigate the relationship between MMP-9 concentrations in blood within 24 hours of stroke onset and subsequent HT of cerebral infarction. Methods— We studied 250 patients with a hemispheric ischemic stroke of 7.8±4.5 hours’ duration. Early CT signs of cerebral infarction were evaluated on admission. The HT and infarct volume were analyzed from the CT performed on days 4 through 7. MMP-9 levels were determined by enzyme-linked immunosorbent assay in blood samples obtained on admission. Results— HT was observed in 38 patients (15.2%): 24 (63.2%) had a hemorrhagic infarction, and 14 (36.8%) had a parenchymal hematoma. A total of 108 patients (43%) received anticoagulants before the second CT scan. Systolic and diastolic blood pressures, body temperature, frequency of early CT signs of ischemia (92% versus 22%), and treatment with anticoagulants (79% versus 37%) were significantly higher in the group with HT ( P 3 in the HT group and 90±68 cm 3 in the group without HT ( P =0.003). Median (quartiles) plasma MMP-9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93] ng/mL, P P =0.014). MMP-9 levels ≥140 ng/mL had a positive and negative predictive value of HT of 61% and 97%, respectively. MMP-9 ≥140 ng/mL was associated with HT (odds ratio, 12; 95% confidence interval, 3 to 51; P Conclusions— High plasma MMP-9 concentration in the acute phase of a cerebral infarct is an independent biochemical predictor of HT in all stroke subtypes.

All authors contributed equally to this work. Susana Arias-Rivas wrote the main paper. Manuel Rodriguez-Yáñez investigated the supplementary data. Julia Cortés and Pablo Aguiar performed the nuclear image studies and analysed and described the neuroimaging results. María Pardo, Rogelio Leira and Jose Castillo jointly conceived the study, followed the patient and prepared the manuscript. Miguel Blanco discussed the results. All authors discussed the results and implications and commented on the manuscript at all stages.

Background and Purpose— No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale ≤1, modified Rankin Scale score ≤1, and Barthel Index ≥95 at 3 months using the generalized estimating equations analysis. Methods— A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale ≥8, and prior modified Rankin Scale score ≤1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified. Results— Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P =0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P =0.0043). The overall safety of citicoline was similar to placebo. Conclusions— Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.

We determined the effect of different exercise training modalities in patients with chronic obstructive pulmonary disease, including strength training (n = 17), endurance training (n = 16), and combined strength and endurance (n = 14) (half of the endurance and half of the strengthening exercises). Data were compared at baseline, the end of the 12-week exercise-training program, and 12 weeks later. Improvement in the walking distance was only significant in the strength group. Increases in submaximal exercise capacity for the endurance group were significantly higher than those observed in the strength group but were of similar magnitude than those in the combined training modality, which in turn were significantly higher than for the strength group. Increases in the strength of the muscle groups measured in five weight lifting exercises were significantly higher in the strength group than in the endurance group but were of similar magnitude than in the combined training group, which again showed significantly higher increases than subjects in the endurance group. Any training modality showed significant improvements of the breathlessness score and the dyspnea dimension of the chronic respiratory questionnaire. In conclusion, the combination of strength and endurance training seems an adequate training strategy for chronic obstructive pulmonary disease patients.

Background and Purpose: Stroke on awakening (SOA) is denied the benefits of thrombolytic therapy and is typically excluded from acute clinical trials on the grounds that the time of onset is unknown. In this study we compared the clinical characteristics of SOA and of stroke while awake (SWA), particularly in the subgroup of patients seen within a time frame of 6 h after stroke awareness. Material and Methods: Patients were included consecutively in the Stroke Data Bank of the Spanish Neurological Society (BADISEN) that records 365 different items, including vascular risk factors, neurological findings, stroke severity, aetiopathogenic diagnosis and neuroimaging data. Results: A total of 1,248 patients with acute cerebral infarction were included in the study, 301 (24.1%) with SOA and 947 (75.9%) with SWA. The peak time for stroke occurrence was between 6:01 a.m. and 12 noon, both in the whole stroke group and in each aetiopathogenic stroke subtype. Age, sex, stroke risk factors, stroke severity at admission, vital signs and stroke subtypes were not significantly different between SOA and SWA, neither in the group as a whole nor in the group of patients seen within 6 h of stroke recognition. Six hundred and fifty-four patients were seen within the potential 6-hour therapeutic window. In this group, the CT scan on admission was normal in 39.4% of SOA but the ultimate CT/MRI scan showed that 46.2% of these had a territorial infarction (in SWA these same figures were 60.8 and 67.7%, respectively). Conclusion: There are no relevant differences in the clinical, neuroimaging and aetiopathogenic characteristics of SOA and SWA. We should rely on new techniques such as DWI/PWI to indicate the most appropriate treatment in a more rational manner as nearly half of the patients with SOA seen early may benefit from them.

Background and Purpose: Stroke is one of the leading causes of death and disability in western countries. Improving attention to stroke demands better public information about the illness. The aim of the present study was to determine the current knowledge of stroke among the Spanish population. Methods: We conducted a population-based telephone interview in Spain. A total of 3,000 respondents were selected at random following a systematic procedure aimed at filling the sex/age community quotas. Results: A total of 16,016 telephone calls were made. Three thousand respondents were eligible and 2,884 completed the telephone interview. Only 4.5% of respondents knew the term stroke, 1,719 (59.6%) participants were able to mention at least one stroke risk factor, and only 940 (32.6%) could mention at least one stroke sign without prompting. Most respondents considered stroke to be a severe and dangerous illness that can be treated, but less than half of the respondents went immediately to a hospital when faced with a stroke event. Suitable stroke knowledge was only achieved by 302 (10.5%) respondents. Those who had home-based occupations and no previous stroke experience were less likely to have suitable stroke knowledge. Conclusions: This study confirms that our community is still unfamiliar with stroke. Wide population-based educational programs are needed to increase public knowledge of stroke. Our results indicate that people with home-based occupations should be the main target of our education campaigns.

We sought to assess the anti-inflammatory properties of unfractionated heparin (UFH) in patients with ischemic stroke treated within 24 h from the onset of symptoms. We studied prospectively 167 patients that received 1000 IU/h intravenous UFH (n=70) or 300 mg oral aspirin (n=97) at a mean treatment delay of 6.7 h. Repeated plasma levels of interleukin (IL)-6, IL-10, IL-4, tumor necrosis factor (TNF)-α, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared in both groups using multivariate analyses. Whereas TNF-α and sICAM-1 decreased at 48 h, IL-6, IL-4, and sVCAM-1 increased compared with baseline values (P

De autorretrato va mi intervencion. Aunque ni fisico ni intelectual, que el primero sobra y el segundo resultaria pretencioso. Os presento, en cambio, mi autorretrato profesoral. El que he ido dibujando durante el cuarto de siglo cumplido en que he impartido ensenanza en esta Facultad. Largo camino y muchas vicisitudes: asambleas, huelgas, grises por los pasillos, algaradas, pancartas, trajes de pana, melenudos, minifaldas, urnas electorales, pantalones vaqueros, graffiti, cabelleras multicolores, piercings, y, en todo tiempo y por todas partes, estudiantes, multitud de estudiantes, estudiosos, vagos, inteligentes, torpes, religiosos, agnosticos, gazmonos, jaraneros, ruidosos, invariablemente ruidosos, de derechas, de izquierdas, indiferentes, de baja y alta cuna

This concluding chapter has been inspired by the chapters on the “state of the art” of the sociology of work in the countries covered in this volume, as well as a number of other, similar reviews published over the last 5 years in Europe and Latin America. In it, I offer seven observations or reflections on the state of the discipline, its social context, and the prospects for the future. I begin by considering the different rhythms and levels of development of the sociology of work and, closely related to these, the social, cultural, academic, and political contexts that shape research agendas and results. The evident trends toward convergence, often more academic than real, of research topics in the different countries, then lead to a consideration of the continued importance of national and international differences, and points of noncommunication stemming from both disciplinary and linguistic divides. In this respect, I highlight what I see as some of the negative implications of the “Babelesque” character of an academic community that is fragmented by its various languages of reference. The chapter ends with some thoughts on the distinct “national paths” of presentation and argumentation that can be seen in the reports on the different countries and their authors’ discursive strategies. Finally, I conclude by pinpointing the trends identified in the different reports that constitute the surest signs of hope for the consolidation of a global academic community of sociologists of work.

La historia del arte presenta desde la perspectiva profesional una situacion ciertamente muy contradictoria. Si bien existe un indiscutible reconocimiento social e institucional sobre la implicacion de nuestra disciplina en el campo del patrimonio historico, acorde con la trayectoria y preparacion cientifica de la misma, en la practica, esta actividad profesional presenta una situacion muy deficiente, caracterizada por su indefinicion, desconsideracion, desregulacion o, incluso, intrusismo profesional, sobre todo en campos como la restauracion, la difusion o el planeamiento de proteccion. A partir de esta constatacion, el texto aborda la estrategia para proceder a un reconocimiento adecuado de la participacion de nuestra disciplina en el campo patrimonial, el cual pasa necesariamente por una reglamentacion normativa de las competencias y responsabilidades de la misma, que debe basarse en la consideracion del patrimonio historico-artistico como una masa patrimonial singular y en la normalizacion de la actividad profesional de la historia del arte en este campo a traves de la emision de informes historico-artisticos. Normal 0 21 false false false ES X-NONE X-NONE

La historia del arte necesita hacer un ejercicio de autoafirmación científica y disciplinar y volver a reclamar un papel central en la tutela como corresponde al que ocupa el patrimonio histórico-artístico dentro de los bienes culturales. Y para recuperar esta centralidad ya no basta argÜir la honorabilidad y el prestigio de una disciplina de gran trayectoria y significación histórica como la nuestra, sino que exige aportar fundamentos, métodos y herramientas a nuestros historiadores para que puedan abordar con garantías y credibilidad las demandas profesionales de la tutela.

Background and Purpose —The mechanisms involved in the neurological deterioration of acute lacunar strokes are unknown. Although accumulating evidence suggests that glutamate release plays a role in the progression of territorial infarctions, it remains to be established whether excitotoxicity also participates in lacunar stroke progression. We investigated whether excitatory and inhibitory amino acid concentrations in blood predict subsequent progressive motor deficits in lacunar infarctions. Methods —We studied 113 consecutive patients with lacunar infarct, defined by clinical and computed tomography/magnetic resonance imaging criteria, within the first 24 hours after stroke onset. Neurological deterioration was defined as a decrease of ≥1 points in the motor items of the Canadian Stroke Scale in the first 48 hours after admission. Glutamate, glycine, and GABA were determined by high-performance liquid chromatography in plasma samples obtained on admission. Predictive values, sensitivity, specificity, and accuracy of specific glutamate and GABA concentrations and glutamate×glycine/GABA index for progression of lacunar stroke were calculated. Results —Twenty-seven patients (23.9%) had neurological worsening. Plasma concentrations of glutamate (253±70 versus 123±73 μmol/L, mean±SD) were higher and those of GABA (140±63 versus 411±97 nmol/L) were lower in the progressing group than in the nonprogressing group (both P 200 μmol/L and GABA levels 106 had a positive predictive value of 85%. Conclusions —These findings suggest that an imbalance between the glutamate and GABA concentrations may play a role in the pathophysiology of progressing lacunar infarctions.

We recently described the syntheses of 12a-c, 4-amino-7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF), and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), in six steps from commercially available p-substituted methyl benzoates in 20-27% overall yields. Such analogues were tested in vitro against CCRF-CEM leukemia cells and showed that they are completely devoid of any activity, the IC(50) being higher than 20 microg/mL for all cases. To clarify if the presence of the carbonyl group in position C7, the distinctive feature of our synthetic methodology, is the reason for this lack of activity, we have now obtained the 7-oxo substituted analogues of 5-DATHF and DDATHF, 18a-c, in 10-30% overall yield. Testing of 18a-c in vitro against CCRF-CEM leukemia cells revealed that these compounds are totally inactive. A molecular modeling study of 18b inside the active site of the complex E. coliGARTFase-5-DATHF-GAR pointed to an electronic repulsion between the atoms of the 7-oxo group and the carbonyl group of Arg90 as a possible explanation for the inactivity of 18a-c.