[Opicapone for the treatment of Parkinson's disease: real-life data in Spain]. / Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.

Opicapone is a catechol-O-methyl-transferase (iCOMT) inhibitor authorized in Europe in 2016 and indicated as adjunctive therapy to preparations of levodopa/ DOPA decarboxylase inhibitors in adult patients with Parkinson's disease and end-of-dose motor fluctuations who cannot be stabilised on those combinations. The efficacy of opicapone in these patients has been demonstrated in two pivotal randomized clinical trials, BIPARK I and BIPARK II, in which it has demonstrated its superiority versus placebo and non-inferiority versus entacapone. Although they constitute the gold standard for the evaluation of interventions, randomized clinical trials present limitations of external validity due to the use of strict eligibility criteria. Therefore, it is considered necessary to have a more comprehensive evaluation of the efficacy of the drug, complementing the information obtained from randomized clinical trials with that of "real world or real clinical practice" studies. The objective of this review has been to collect and put into perspective the information available on opicapone coming from real clinical practice studies in Spain. The data from Spain with opicapone in 18 series with more than 1,000 patients in total, confirm the safety and efficacy previously reported with this iCOMT. Furthermore, they show that opicapone is especially useful in patients with a less advanced stage of the disease and mild motor fluctuations, which would suggest that the earlier its introduction in the therapeutic scheme for the management of motor fluctuations, the better is the benefit-risk ratio for the drug.

TITLE: Opicapona para el tratamiento de la enfermedad de Parkinson: datos de vida real en España.Resumen. La opicapona es un inhibidor de la catecol-O-metiltransferasa (iCOMT) autorizado en Europa en 2016 como terapia adyuvante a las preparaciones de levodopa/inhibidores de la dopa descarboxilasa en pacientes adultos con enfermedad de Parkinson y fluctuaciones motoras de final de dosis que no puedan ser estabilizados con esas combinaciones. La eficacia de la opicapona en estos pacientes ha sido demostrada en dos ensayos clínicos pivotales, BIPARK I y BIPARK II, en los que se ha demostrado la superioridad frente al placebo y la no inferioridad frente a la entacapona. A pesar de que constituyen el estándar para la evaluación de intervenciones, los ensayos clínicos aleatorizados presentan limitaciones de validez externa debidas a la utilización de criterios estrictos de elegibilidad. Por tanto, se considera necesario disponer de una evaluación más amplia de la eficacia general del fármaco, complementando la información de los ensayos clínicos aleatorizados con estudios de 'vida real o práctica clínica real'. El objetivo de esta revisión ha sido recopilar y poner en perspectiva la información disponible sobre los resultados de la opicapona en estudios de práctica clínica real en España. Los datos acumulados en España con opicapona en 18 series con más de 1.000 pacientes confirman la seguridad y la eficacia de este iCOMT comunicadas previamente. Además, muestran que la opicapona es especialmente útil en pacientes en un estadio de la enfermedad menos avanzado y fluctuaciones motores leves, lo que sugeriría una mejor relación beneficio-riesgo cuanto más temprana sea su introducción en el esquema terapéutico para el tratamiento de las fluctuaciones motoras.

LAM study: Effects of lacosamide on behaviour and quality of life in patients with epilepsy. / Estudio LAM: conducta y calidad de vida en pacientes diagnosticados de epilepsia tratados con lacosamida.

INTRODUCTION: Psychiatric comorbidities are common in epileptic patients, and evaluating the impact of antiepileptic drugs on patients' moods is therefore essential. The aim of this study is to assess the effects of lacosamide on behaviour and quality of life in people with epilepsy. METHODS: We conducted a multicentre prospective observational study of poorly-controlled epileptic patients who received lacosamide as an adjuvant treatment. Patients were evaluated on 4 occasions during a 12-month period. The impact of lacosamide on patients' mood and quality of life was assessed with the Quality of Life in Epilepsy Inventory-10 (QOLIE-10), the Hospital Anxiety and Depression Scale (HADS), and the Barratt Impulsiveness Scale (BIS-11). As a secondary objective, we evaluated the effectiveness and safety of lacosamide. RESULTS: We included 55 patients with a mean age of 47.1±18.4 years. At baseline, 34.5% of the patients had psychiatric comorbidities; the mean number of crises in the previous month was 3.6±4.3. The QOLIE-10 and HADS scales revealed statistically significant improvements in patients with a poor baseline condition (anxiety, depression, and/or poor quality of life). The BIS-11 scale detected no impulsive behaviour during follow-up. After 12 months of treatment, 51.9% of the patients were seizure-free and 77.8% experienced a reduction of at least 50% in seizure frequency. Adverse effects were mild in most cases; lacosamide was discontinued in 10 patients (18.2%). CONCLUSIONS: Lacosamide is a safe and effective treatment option for patients with epilepsy and psychiatric comorbidities.

Utilidad de los nuevos esquemas de agrupación de los grados de Fuhrman en la práctica clínica para el tumor renal de células claras / Usefulness of New Schemes to Group Fuhrman Grades in Clinical Practice for Clear Cell Renal Tumour

Objetivo: Evaluar si la re-clasificación de los carcinomas renales de células claras (CRCC) en dos o tres grados de Fuhrman (GF) frente a la clasificación clásica mantiene su valor pronóstico. Material y métodos: Estudio sobre una cohorte de 383 CRCC tratados con nefrectomía radical/parcial (1990-2009). Se analizaron datos demográficos, evolución y supervivencia de los pacientes. Un uropatólogo reasignó los grados de Fuhrman de forma ciega al informe original. Para estudiar si se mantenía el valor pronóstico con las distintas clasificaciones se realizaron tres análisis de regresión múltiple de Cox, categorizando la variable grado en 4 categorías (I-II-III-IV), en tres (I+II-III-IV) y en dos (I+II-III+IV). Las variables explicativas fueron: edad, sexo, tamaño tumoral, estadio y grado. Las variables respuesta fueron: tiempo de supervivencia libre de progresión (recidiva locorregional /metástasis) y de supervivencia cáncer-específica. Resultados: La mediana de supervivencia global fue de 125 meses (IC 95%: 92-159). En los tres análisis multivariantes el grado de Fuhrman demostró valor predictivo independiente (p=0,0001) frente al estadio para la supervivencia libre de progresión y supervivencia cáncer-específica. El valor pronóstico se mantuvo en las nuevas clasificaciones. En la de tres categorías el paso del grado I+II al III presentó un RR: 2,31(p=0,0001) y del grado III al IV un RR: 2,47(p=0,0001) y en la de dos categorías se observó un RR: 2,8 (p=0,001) al pasar del grado I+II al III+IV. Conclusiones: La categorización en dos o tres grupos del grado de Fuhrman mantiene la capacidad predictiva sobre la supervivencia libre de progresión y cáncer-específica. Los grados III y IV presentan evoluciones distintas, por lo que la clasificación en tres categorías parece más adecuada para describir la evolución de estos pacientes (AU)

Objective: To evaluate if re-grading renal cell carcinoma (CRCC) in two or three-tiered grading schemes versus the traditional Fuhrman classification maintains the same prognostic value. Material and methods: A study of a cohort of 383 treated CRCC with radical or partial nephrectomy between 1990-2009 was made. We analyzed the demographic data, evolution and survival of these patients. An uropathologist reassigned the Fuhrman grades blindly to the first classification. In order to study if the prognostic value was maintained with the different classification, three Cox multivariate regression analysis were performed, classifying the variable of grade into four categories: (I-II-III-IV), into three (I+II-III-IV) and into two (I+II-III+IV). The explanatory variables were: age, gender, tumor size, study stage and grade. The response variables were progression-free survival (local-regional recurrence/metastasis) and cancer specific survival time. Results: The median overall survival was 125 months (95% CI: 92-159). In the three multivariate analyses carried out, the Fuhrman classification showed independent predictive value (p=:0.0001) compared to progression-free survival and cancer specific survival. The predictive power was maintained in the new classifications. In the three categories, the changing from grade I+II to III meant RR: 2.31 (p=0.0001) and from grade III to IV RR: 2.47 (p=0.0001) and in two-tiered classification an RR: 2.8 (p=0.001) was found when changing from I+II to III+IV. Conclusions: Our results show that categorizing the Fuhrman grade into three or two-tiered grading schemes provide the same predictive accuracy on progressive free survival and cancer specific survival. Grades III and IV have different outcomes so that the three-tiered classification seems to be more appropriate to described the course of these patients (AU)

Daidzein has neuroprotective effects through ligand-binding-independent PPARγ activation.

Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidzein. Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action have not been fully elucidated. In this context, it has been postulated that phytoestrogens might activate the peroxisome proliferator-activated receptor-γ (PPARγ), which exerts neuroprotective effects in several settings. The aim of this study was to determine whether the phytoestrogen daidzein elicits beneficial actions in neuronal cells by mechanisms involving activation of PPARγ. Our results show that daidzein (0.05-5 µM) decreases cell death induced by exposure to oxygen-glucose deprivation (OGD) from rat cortical neurons and that improves synaptic function, in terms of increased synaptic vesicle recycling at nerve terminals, being both effects inhibited by the PPARγ antagonist T0070907 (1 µM). In addition, this phytoestrogen activated PPARγ in neuronal cultures, as shown by an increase in PPARγ transcriptional activity. Interestingly, these effects were not due to binding to the receptor ligand site, as shown by a TR-FRET PPARγ competitive binding assay. Conversely, daidzein increased PPARγ nuclear protein levels and decreased cytosolic ones, suggesting nuclear translocation. We have used the receptor antagonist (RE) fulvestrant to study the neuroprotective participation of daidzein via estrogen receptor and at least in our model, we have discarded this pathway. These results demonstrate that the phytoestrogen daidzein has cytoprotective properties in neurons, which are due to an increase in PPARγ activity not mediated by direct binding to the receptor ligand-binding domain but likely due to post-translational modifications affecting its subcellular location and not depending to the RE and it is not additive with the agonist rosiglitazone.

[Usefulness of new schemes to group Fuhrman grades in clinical practice for clear cell renal tumour]. / Utilidad de los nuevos esquemas de agrupación de los grados de Fuhrman en la práctica clínica para el tumor renal de células claras.

OBJECTIVE: To evaluate if re-grading renal cell carcinoma (CRCC) in two or three-tiered grading schemes versus the traditional Fuhrman classification maintains the same prognostic value. MATERIAL AND METHODS: A study of a cohort of 383 treated CRCC with radical or partial nephrectomy between 1990-2009 was made. We analyzed the demographic data, evolution and survival of these patients. An uropathologist reassigned the Fuhrman grades blindly to the first classification. In order to study if the prognostic value was maintained with the different classification, three Cox multivariate regression analysis were performed, classifying the variable of grade into four categories: (I-II-III-IV), into three (I+II-III-IV) and into two (I+II-III+IV). The explanatory variables were: age, gender, tumor size, study stage and grade. The response variables were progression-free survival (local-regional recurrence/metastasis) and cancer specific survival time. RESULTS: The median overall survival was 125 months (95% CI: 92-159). In the three multivariate analyses carried out, the Fuhrman classification showed independent predictive value (p=:0.0001) compared to progression-free survival and cancer specific survival. The predictive power was maintained in the new classifications. In the three categories, the changing from grade I+II to III meant RR: 2.31 (p=0.0001) and from grade III to IV RR: 2.47 (p=0.0001) and in two-tiered classification an RR: 2.8 (p=0.001) was found when changing from I+II to III+IV. CONCLUSIONS: Our results show that categorizing the Fuhrman grade into three or two-tiered grading schemes provide the same predictive accuracy on progressive free survival and cancer specific survival. Grades III and IV have different outcomes so that the three-tiered classification seems to be more appropriate to described the course of these patients.

Soy-derived phytoestrogens as preventive and acute neuroprotectors in experimental ischemic stroke: influence of rat strain.

The ability of a soy-based high-phytoestrogen diet (nutritional intervention) or genistein (pharmacological intervention), to limit ischemic brain damage in Wistar, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, has been assessed. As to the nutritional intervention, two groups from each strain received either a phytoestrogen-free (PE-0) or a high-phytoestrogen (PE-600) diet from weaning to adulthood. As to the pharmacological intervention, all animals were fed the standard soy-free AIN-93G diet and subsequently separated into two groups from each strain to receive either pure genistein (aglycone form, 1mg/kg/day intraperitoneal) or vehicle at 30 min reperfusion. After an episode of 90 min ischemia (intraluminal thread procedure) followed by 3 days reperfusion, cerebral infarct volume was measured. Arterial blood pressure (ABP) was significantly higher at the basal stage (just before ischemia) in SHR (140 ± 7 mmHg, n=17, p<0.05) than in Wistar (113 ± 4mmHg, n=23) and WKY (111 ± 6mmHg, n=14) rats. No significant differences were shown among the three stages (basal, ischemia, reperfusion) within each rat strain for both PE-0 and PE-600 diets. Wistar, but not WKY or SHR, rats fed the PE-600 diet showed significantly lower infarct volumes than their counterparts fed the PE-0 diet (30 ± 3% vs. 17 ± 3%, p<0.01). Genistein-treated Wistar, but not WKY or SHR, rats showed significantly lower infarct volumes than their vehicle-treated controls (27 ± 2% vs. 15 ± 2%, p<0.01). Our results demonstrate that: (1) the neuroprotective action of either chronic or acute exposure to soy isoflavones is strain-dependent, since it was shown in Wistar but not WKY or SHR rats; and (2) the soy-based diet does not prevent development of hypertension in SHR rats.

Guía de recomendaciones en la aplicación de modelos animales para el estudio del ictus / Recommendations guide for experimental animal models in stroke research

Introducción: La búsqueda de una terapia neuroprotectora efectiva para el ictus sigue siendo un reto para investigadores y clínicos. Una de las causas principales por la que a nivel clínico han fracasado terapias eficaces en ensayos experimentales reside probablemente en el desarrollo y modo de evaluación en estudios preclínicos de los agentes neuroprotectores en los modelos animales de isquemia cerebral. Métodos: Para unificar la metodología en la aplicación de los modelos experimentales a nivel nacional y mejorar la investigación en este campo, se ha elaborado un documento entre varios grupos españoles expertos en investigación neurovascular que constituye una guía de recomendaciones para el uso de los mismos. Resultados: Sus aspectos fundamentales se basan en la selección del modelo más adecuado en función del objetivo del estudio, teniendo en cuenta el tipo de especie y la cepa animal, la edad, el sexo y los factores de riesgo. La realización del diseño experimental incluye un grupo sham control y el cálculo previo del tamaño muestral. Otros aspectos muy importantes a seguir son la aleatorización en la asignación de los animales en cada grupo, el análisis ciego de los parámetros estudiados, el registro de la temperatura y flujo sanguíneo cerebral, así como la notificación y causas de animales excluidos en el estudio y la tasa de mortalidad. Conclusiones: Es esencial adquirir compromisos metodológicos para la optimización del empleo de los modelos animales de isquemia cerebral que incremente el rendimiento de hallazgos positivos en la fase preclínica y puedan trasladarse a la práctica clínica (AU)

Introduction: The progress of effective therapies for stroke has become a challenging task for both researchers and clinicians. Some pitfalls in clinical trials might have their origins in the pre-clinical experimental ischaemic models for the evaluation of potential neuro-protective agents. Methods: We aim to standardise the methods for the development of stroke animal models throughout Spain, to produce document with appropriate recommendations and best practice in order to improve experimental methods in the field of stroke research. Results: Members of several experienced stroke research groups prepared a guide with recommendations in the application of focal cerebral ischaemic models. The main features of this guide are based on the selection of the most appropriate animal model, taking in account the objective of the study, the species, strain, age, sex of animals, as well as risk factors. The experimental design must include a sham control group and the sample size calculation. Animal randomisation and blind analysis, masked assessment of outcomes, monitoring of body temperature and cerebral blood flow, and the reporting of reasons for excluding animals from the study, as well as the mortality rate, are other main points to fulfil in the application of stroke models.Conclusions: Standardised methods are essential to increase the success of the pre-clinical findings in the stroke neuroprotection field to be able to translate to the clinical practice (AU)

Recommendations guide for experimental animal models in stroke research.

INTRODUCTION: The progress of effective therapies for stroke has become a challenging task for both researchers and clinicians. Some pitfalls in clinical trials might have their origins in the pre-clinical experimental ischaemic models for the evaluation of potential neuro-protective agents. METHODS: We aim to standardise the methods for the development of stroke animal models throughout Spain, to produce document with appropriate recommendations and best practice in order to improve experimental methods in the field of stroke research. RESULTS: Members of several experienced stroke research groups prepared a guide with recommendations in the application of focal cerebral ischaemic models. The main features of this guide are based on the selection of the most appropriate animal model, taking in account the objective of the study, the species, strain, age, sex of animals, as well as risk factors. The experimental design must include a sham control group and the sample size calculation. Animal randomisation and blind analysis, masked assessment of outcomes, monitoring of body temperature and cerebral blood flow, and the reporting of reasons for excluding animals from the study, as well as the mortality rate, are other main points to fulfil in the application of stroke models. CONCLUSIONS: Standardised methods are essential to increase the success of the pre-clinical findings in the stroke neuroprotection field to be able to translate to the clinical practice.

Aplicación de niveles asistenciales de rehabilitación psicofuncional en un centro de día para personas dependientes / Application of health care levels of psychofunctional rehabilitation in a day center for dependent persons

El objetivo de este estudio es un ensayo para la aplicación de actividades integradoras mediante un programa psicofuncional en el que están integradas las actividades propias de la rehabilitación física y de la estimulación cognitiva. De esta manera los diferentes profesionales del centro de día se coordinan entre sí mediante un programa de atención personalizado, asumiendo las cargas asistenciales y facilitando a las familias el apoyo y el asesoramiento adecuados.En Geriser Centros de Día se aplica al ingreso de los pacientes un protocolo de valoración psicofuncional que nos definirá los cinco niveles asistenciales en función del deterioro físico y/o cognitivo que presenten.Es importante destacar la puesta en marcha de estos programas que ayudan a mantener la calidad de vida de los pacientes y sus cuidadores y nos invite a profundizar en el diseño de nuestros centros, basados en una orientación terapéutica para nuestros clientes y protésica para sus familiares (AU)

Administration of transforming growth factor-alpha reduces infarct volume after transient focal cerebral ischemia in the rat.

Growth factors promote cell growth and survival and protect the brain from developing injury after ischemia. In this article, the authors examined whether transforming growth factor-alpha (TGF-alpha) was protective in transient focal ischemia and whether alteration of cerebral circulation was involved. Rats received intraventricular TGF-alpha (50 ng, either split into 2 doses given 30 minutes before and 30 minutes after middle cerebral artery occlusion (MCAO), or 1 dose given 30 minutes after MCAO) or vehicle. Rats were subjected to 1-hour intraluminal MCAO and cerebral blood flow was recorded continuously by laser-Doppler flowmetry. Infarct volume was measured 1 and 4 days later. The effects of TGF-alpha on arterial tone were assessed in isolated rabbit basilar and common carotid arteries. Transforming growth factor-alpha before and after ischemia reduced infarct volume by 70% at 1 day and 50% at 4 days. Transforming growth factor-alpha given only after ischemia also did reduce infarct volume by 70% at 1 day and 80% at 4 days. The protective effect was more marked in cortex than in striatum. Transforming growth factor-alpha did not change cortical microvascular perfusion and did not modify arterial passive tone nor agonist-induced active tone. It can be concluded that TGF-alpha reduces infarct volume, even when the factor is exclusively administered at reperfusion, and that this effect is not mediated by changes in microvascular perfusion or cerebral arteries. It is therefore suggested that TGF-alpha has a protective effect against neuronal cell death after transient focal ischemia.

Temporospatial expression of HSP72 and c-JUN, and DNA fragmentation in goat hippocampus after global cerebral ischemia.

The role of gene induction (expression of HSP72 and c-JUN proteins) and delayed ischemic cell death (in situ labeling of DNA fragmentation) have been investigated in the goat hippocampus after transient global cerebral ischemia. The animals were subjected to 20-min ischemia (bilateral occlusion of the external carotid arteries plus bilateral jugular vein compression) and allowed to reperfuse for 2 h, and then 1, 3, and 7 days. Histological signs of cell loss were not found in the hippocampus at 2 h, 1 day, or 3 days of reperfusion. However, such an ischemic insult produced extensive, selective, and delayed degeneration in the hippocampus, as 68% of the neurons in CA1 had died at 7 days, but cell loss was not detected in CA3 and dentate gyrus fields. Concomitantly, a high percentage of TUNEL-positive CA1 neurons (60+/-9%, mean +/- SEM) was seen at 7 days, but not at the earlier time points. Mild induction of HSP72 was detected in the goat hippocampus after ischemia. The maximum percentage of HSP72-positive neurons (10-15%) was shown at 3 days of reperfusion and was concentrated mainly in the CA3 field, subiculum, and hilus, rather than in the CA1 field, whereas HSP72 expression was hardly detected at 7 days. At this later time point, scattered induction of nuclear c-JUN was found in a few neurons. The results show that: 1) postischemic delayed neuronal death selectively affects the CA1 field in the goat hippocampus, a phenomenon which seems to take longer to develop than in previously reported rodent models; and 2) postischemic expression of c-JUN does not appear to be related to cell death or survival, while the inability of most CA1 neurons to express HSP72 could contribute to neuronal death.

Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry inhibition.

Estrogens account for gender differences in the incidence and outcome of stroke, but it remains unclear to what extent neuroprotective effects of estrogens are because of parenchymal or vascular actions. Because reproductive steroids have vasoactive properties, the authors assessed the effects and mechanisms of action of 17-beta-estradiol in rabbit isolated basilar artery. Cumulative doses of 17-beta-estradiol (0.3 micromol/L to 0.1 mmol/L) induced concentration-dependent relaxation that was larger in basilar than carotid artery, in male than female basilar artery, and in KCl-precontracted than UTP-precontracted male basilar artery. Endothelium removal did not modify relaxation induced by 17-beta-estradiol in basilar artery, whereas relaxation induced by acetylcholine (1 nmol/L to 0.1 mmol/L) was almost abolished. Neither the estrogen receptor antagonist ICI 182,780 (1 micromol/L), nor the protein synthesis inhibitor cycloheximide (1 micromol/L) affected 17-beta-estradiol-induced relaxations. Relaxations induced by the K(+) channel openers NS1619 and pinacidil in the same concentration range were greater and lower, respectively, when compared with relaxation to 17-beta-estradiol, which was not significantly modified by incubation with the K(+) channel blockers charybdotoxin (1 nmol/L and 0.1 micromol/L) or glibenclamide (10 nmol/L and 1 micromol/L). Preincubation with 17-beta-estradiol (3 to 100 micromol/L) produced concentration-dependent inhibition of CaCl(2)-induced contraction, with less potency than the Ca(2+) entry blocker nicardipine (0.01 to 10 nmol/L). The authors conclude that 17-beta-estradiol induces endothelium-independent relaxation of cerebral arteries with tissue and gender selectivity. The relaxant effect is because of inhibition of extracellular Ca(2+) influx to vascular smooth muscle, but activation of estrogen receptors, protein synthesis, or K(+) efflux are not involved. Relatively high pharmacologic concentrations of 17-beta-estradiol causing relaxation preclude acute vascular effects of physiologic circulating levels on the cerebral circulation.

La estimulación continua en la enfermedad de Alzheimer y otras demencias, en un Centro de Día y Rehabilitación / Continuos stimulation in Alzheimer´s disease and other dementias accomplished in a dalily care center and rehabilitation

En la enfermedad de Alzheimer y en las demencias, la relación entre incapacidad funcional y los síntomas comportamentales y cognitivos no es siempre lineal. Podemos encontrarnos con pacientes muy incapacitados funcionalmente que muestran poco afectación cognitiva. Basaremos nuestra terapia en la estimulación continua mediante técnicas de orientación a la realidad, realizadas en un Centro Día por un equipo asistencial integrado. Junto a estas técnicas integraremos la rehabilitación física y la estimulación cognitiva sin establecer diferencias entre unas y otras ya que la rehabilitación en el Alzheimer es un conjunto de técnicas físicas de estimulación psicológica y de hábitos. Se estudia una población de 298 pacientes atendidos entre enero de 1998 y enero del 2000, que cumplieron más de 6 meses de tratamiento. Reagrupados según su nivel de deterioro físico y psíquico en 5 niveles asistenciales. Se analizaron como variables: tipo de demencia, niivel asistencial, sexo, patologías asociadas, causa de baja y satisfacción de la familia y terapeutas. Tras el análisis de los resultados y la discusión llegamos entre otras a conclusiones como: 1. El grado de satisfacción de los familiares y terapeutas es elevado; 2. Durante los 6 meses de tratamiento no se produjeron cambios de nivel asistencial; 3. Una correcta evaluación y clasificación por niveles permiten un mejor manejo socio-sanitario (AU)

Reduction of infarct size by the NO donors sodium nitroprusside and spermine/NO after transient focal cerebral ischemia in rats.

Nitric oxide (NO) plays a dual role (neuroprotection and neurotoxicity) in cerebral ischemia. NO promoting strategies may be beneficial shortly after ischemia. Therefore, we have studied the hemodynamic and possible neuroprotective effects of two NO donors, the classical nitrovasodilator sodium nitroprusside (SNP) and the NONOate spermine/NO, after transient focal cerebral ischemia in rats. Parietal cortical perfusion was measured by laser-Doppler flowmetry. The effects of increasing intravenous doses (10-300 microgram) of sodium nitroprusside and spermine/NO on cortical perfusion and arterial blood pressure were assessed. Transient (2 h) focal cerebral ischemia was carried out by the intraluminal thread method. The effects of intraischemic intravenous infusion of SNP (0.11, 1.1 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) on hemodynamic parameters and infarct size developed after 1 week reperfusion were assessed. In control conditions, SNP and, to a lesser extent, spermine/NO induced dose-dependent hypotension and concomitant reduction in cortical perfusion. In focal cerebral ischemia, infusion of SNP (0.11 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) reduced the infarct size. In the case of spermine/NO, cortical perfusion was maintained above the control levels during the ischemic insult. No significant hypotension was elicited by NO donors at the dose-ratios infused. In conclusion, brain damage induced by transient focal ischemia is reduced by intravenous NO donors. Neuroprotective effects of spermine/NO are due at least in part to improvement of brain perfusion, while sodium nitroprusside must provide direct cytoprotection. These results give further support to the protective effect of NO in the early stages of cerebral ischemia and point to the therapeutic potential of NONOates in the management of brain ischemic damage.

Eficacia del tratamiento de pseudoartrosis en angulación anterolateral congénita de tibia y/o peroné: Hospital Ortopédico Infantil, Caracas, mayo 1948 - mayo 1999 / Effectiveness of the pseudoartrosis treatment in congenital anterolateral bowing of tibia and/or fibula: Infantile Orthopedic Hospital, Caracas, may 1948 - may 1999

La pseudoartrosis congénita de tibia y/o peroné (PCT y/o P) es una patología de baja frecuencia. Representa un problema a escala mundial. Debido a sus dificultades terapéuticas y casos limitados, su estudio es un reto para el cirujano ortopédico. Evaluar la eficacia del tratamiento de la PCT y/o P en pacientes que acudieron al Hospital Ortopédico Infantil entre 1948 y 1999. Estudio restrospectivo correlacional de 23 pacientes con pseudoartrosis congénita de tibia y peroné, considerando: incidencia de enfermedad, factores causales, clasificación según Boyd, tratamiento aplicado y evolución de la enfermedad según Morrisst. 24 casos de pseudoartrosis congénita de tibia y/o peroné fueron estudiados. Predominó el sexo masculino 2:2; el 90,9 por ciento pertenecían al tipo II de Boyd; el 54,2 por ciento presentaba neurofibromatosis y el 20,2 por ciento tenía antecedentes familiares de neurofibromatosis. La técnica quirúrgica más utilizada fue Williams modificado (47,5 por ciento) con un 80,0 por ciento de buenos resultados. El seguimiento promedio de nuestra serie fue de 10,11 años, 20,83 por ciento. Fueron injertados con médula ósea percutáneo. El resultado de los diversos tratamientos fue bueno en el 62,5 por ciento de los pacientes. La Técnica Modificada de Williams reforzada con injertos de médula ósea percutáneo es el tratamiento de elección en PCT y/o P

Cerebrovascular effects of dotarizine, a piperazine derivative, in the goat. An in vivo and in vitro complementary study.

The effects of dotarizine (1-(diphenylmethyl)-4-[3-(2-phenyl-1,3- dioxolan-2-yl)propyl]-piperazine, CAS 84625-59-2) on the cerebral circulation of goats were assessed in vivo by recording continuously global cerebral blood flow (gCBF) and cortical perfusion (CP), and in vitro by recording isometric tension in goat isolated middle cerebral artery (MCA). Administration of dotarizine (1 microgram-5 mg) directly into the cerebroarterial supply of goats produced transient increases in gCBF and CP, and decreases in cerebral vascular resistance (CVR) which were significant for the highest doses tested: 1, 3 and 5 mg. On the other hand, cumulative addition of increasing concentrations of dotarizine (10(-8)-3 x 10(-5) mol/l) to MCA segments subjected to the resting tone of 1 g did not induce sizeable changes in vascular tension; by contrast, dotarizine elicited concentration-dependent relaxations of MCA segments subjected to the active tone induced by either 5-hydroxytryptamine (10(-6) mol/l) or high-K+ medium (50 mmol/l). These results show that dotarizine exerts a direct relaxant action on cerebral arteries, which results in an improvement of cerebral perfusion.

[Extracranial meningioma presenting as a polyp of the outer ear canal]. / Meningioma extracraneal que se manifiesta como pólipo de conducto auditivo externo.

Meningiomas are the most frequent benign intracranial tumor. Up to 20% of these neoplasms may eventually extend beyond the skull, particularly when tumor spread affects the temporal bone. We report a clinicopathological observation of an extracranial meningothelial meningioma that was diagnosed morphologically using immunohistochemical techniques. The tumor presented as polyp in the ear canal of a 70-year-old woman who had a history of ear disease and seizures and was under medical treatment. The growth was associated with a right temporal lobe tumor involving the petrosal bone that had been detected 6 years earlier on computed axial tomography.

Nitric oxide is involved in anoxic preconditioning neuroprotection in rat hippocampal slices.

Sublethal anoxia/ischemia protects against subsequent damaging insults in intact brain or hippocampal slices. To help further understand mechanisms underlying anoxic/ischemic preconditioning, we tested three hypotheses which were that: (a) anoxic preconditioning (APC) improves electrical recovery in rat hippocampal slices; (b) anoxic preconditioning requires nitric oxide (NO); and (c) anoxic preconditioning blocks mitochondrial dysfunction that occurs following re-oxygenation after anoxia. Control hippocampal slices underwent a single 'test' anoxic insult. Experimental slices were preconditioned by 3 short anoxic insults prior to the 'test' insult. Evoked potentials (EPs), and NADH redox status were recorded prior to, during and after preconditioning and/or 'test' anoxic insults. To examine the role of NO, studies sought to determine whether APC could be produced by the NO donor, DEA/NO, and whether APC could be inhibited by NO synthase (NOS) inhibitor (7-nitroindazole). EP amplitudes recovered significantly better after reoxygenation in preconditioned slices and after NO-emulated preconditioning (90.0+/-17.7% and 90.0+/-21.3%, respectively, n=9, ** p<0.01, vs. 17.0+/-7.9%, n=9, in control slices). Inhibition of NOS blocked APC protection (6.8+/-6.8%, n=9). The intensity of NADH hyperoxidation was not significantly different among groups following 'test' anoxia. These data confirm that preconditioning by anoxia improves electrical recovery after anoxia in hippocampal slices. Evidence supports that NO from constitutive hippocampal NOS may be involved in the neuroprotection afforded by preconditioning by a mechanism that does not change the apparent mitochondrial hyperoxidation after anoxia.

Relaxant effects of sodium nitroprusside and NONOates in goat middle cerebral artery: delayed impairment by global ischemia-reperfusion.

Global cerebral ischemia and subsequent reperfusion induce early impairment of the vasodilator responses to hypercapnia and vasoactive substances. Nitric oxide (NO) is involved in the regulation of cerebral blood flow (CBF) in both health and disease. The present study was designed to assess possible changes in the cerebrovascular reactivity to NO donors induced by cerebral ischemia-reperfusion in goats. Female goats (n = 9) were subjected to 20 min global cerebral ischemia under halothane/N2O anesthesia. Sixteen additional goats were sham-operated as a control group. One week later the effects of ischemia-reperfusion on relaxations to NO donors sodium nitroprusside (SNP), diethylamine/NO (DEA/NO), diethylenetriamine/NO (DETA/NO), and spermine/NO (SPER/NO) were studied in rings of middle cerebral artery (MCA) isolated in an organ bath for isometric tension recording. SNP, DEA/NO, DETA/NO, and SPER/NO induced concentration-dependent relaxations of MCA precontracted with KCl (DEA/NO > SPER/NO > SNP > DETA/NO) or with endothelin-1 (DEA/NO > SNP > SPER/NO > DETA/NO). Relaxations were always higher in endothelin-1-precontracted arteries. One week after cerebral ischemia concentration-response curves to SNP and DEA/NO were displaced to the right, indicating a reduction in relaxant potency of NO donors. The classical nitrovasodilator SNP and NONOates induce relaxation of isolated goat MCA which is partially inhibited by arterial depolarization. Global cerebral ischemia followed by reperfusion induces delayed impairment of the relaxant effects of NO on cerebrovascular smooth muscle, which results in reduced vasodilatory potency of NO donors in large cerebral arteries.