EARLY-ESLI study: Long-term experience with eslicarbazepine acetate after first monotherapy failure.

PURPOSE: Evaluate real-life experience with eslicarbazepine acetate (ESL) after first monotherapy failure in a large series of patients with focal epilepsy. METHOD: Multicentre, retrospective, 1-year, observational study in patients older than 18 years, with focal epilepsy, who had failed first antiepileptic drug monotherapy and who received ESL. Data from clinical records were analysed at baseline, 3, 6 and 12 months to assess effectiveness and tolerability. RESULTS: Eslicarbazepine acetate was initiated in 253 patients. The 1-year retention rate was 92.9%, and the final median dose of ESL was 800 mg. At 12 months, 62.3% of patients had been seizure free for 6 months; 37.3% had been seizure free for 1 year. During follow-up, 31.6% of the patients reported ESL-related adverse events (AEs), most commonly somnolence (8.7%) and dizziness (5.1%), and 3.6% discontinued due to AEs. Hyponatraemia was observed in seven patients (2.8%). After starting ESL, 137 patients (54.2%) withdrew the prior monotherapy and converted to ESL monotherapy; 75.9% were seizure free, 87.6% were responders, 4.4% worsened, and 23.4% reported ESL-related AEs. CONCLUSION: Use of ESL after first monotherapy failure was associated with an optimal seizure control and tolerability profile. Over half of patients were converted to ESL monotherapy during follow-up.

A randomized clinical trial of oral versus intravenous methylprednisolone for relapse of MS.

BACKGROUND: Steroids improve multiple sclerosis (MS) relapses but therapeutic window and dose, frequency and administration route remain uncertain. OBJECTIVE: The objective of this paper is to compare the clinical and radiologic efficacy, tolerability and safety of intravenous methylprednisolone (ivMP) vs oral methylprednisolone (oMP), at equivalent high doses, for MS relapse. METHODS: Forty-nine patients with moderate or severe relapse within the previous 15 days were randomized in a double-blind, noninferiority, multicenter trial to receive ivMP or oMP and their matching placebos. Expanded Disability Status Scale (EDSS) scores were determined at baseline and weeks 1, 4 and 12. Brain MRI were assessed at baseline and at weeks 1 and 4. Primary endpoint was a noninferiority assessment of EDSS improvement at four weeks (noninferiority margin of one point), with further key efficacy assessments of number and volume of T1 gadolinium-enhancing (Gd+), and new or enlarged T2 lesions at four weeks' post-treatment initiation. Secondary outcomes were safety and tolerability. RESULTS: The study achieved the main outcome of noninferiority at four weeks for improved EDSS score. No differences were found between ivMP and oMP in the number of Gd+ lesions (0 (0-1) vs 0 (0-0.5), p = 0.630), volume of Gd+ lesions (0 (0-88.0) vs 0 (0-32.9) mm(3), p = 0.735), or new or enlarged T2 lesions (0 (0-194) vs 0 (0-123), p = 0.769). MP was well tolerated, and no serious adverse events were reported. CONCLUSIONS: This study provides confirmatory evidence that oMP is not inferior to ivMP in reducing EDSS, similar in MRI lesions at four weeks for MS relapses and is equally well tolerated and safe. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00753792.

Efficacy and safety of eslicarbazepine-acetate in elderly patients with focal epilepsy: Case series.

PURPOSE: Eslicarbazepine-acetate (ESL) is a third generation antiepileptic drug licensed as adjunctive therapy in adults with focal seizures. Efficacy and safety of ESL have been established in real-life setting. However, data about outcomes in elderly patients are scarce. Primary endpoint was to evaluate outcomes of ESL in elderly patients. METHOD: This was a retrospective survey that included patients >65years with focal seizures who started ESL between January 2010 and July 2012 at 12 Spanish Hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1year. These patients were included within the bigger study ESLIBASE. RESULTS: We included 29 patients, most of them males (18). Mean age was 71.2 year-old and epilepsy evolution was 20 years. Eighteen were pharmacorresistant at baseline. At 12 months, the mean dose was 850mg/day, the retention rate 69%, the responder rate 62% and 24.1% were seizure-free. At 12 months, 16 patients (55.2%) had ≥1 adverse effect (AE), that led to discontinuation in 7 patients. Dizziness, nausea and ataxia were the most common AEs. The tolerability profile improved in 4/5 patients who switched from carbamazepine (CBZ) or oxcarbazepine (OXC) to ESL due to AEs. CONCLUSIONS: ESL was well-tolerated and effective in elderly patients in a real-life setting over 1year, with a dose around 800mg/day. AE effects improved in most of who switched from CBZ or OXC to ESL.

Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: The FYDATA study.

BACKGROUND: Real-world data of current antiepileptic drugs (AEDs) used to treat focal seizures is of importance to understand the efficacy and safety outside of the clinical trial setting. Here we report real-world data from a large series of patients treated with perampanel for 1year. METHODS: FYDATA was a multicentre, retrospective, 1-year observational study assessing the efficacy and safety of adjuvant perampanel in patients ≥12 years of age with focal epilepsy in a real-world setting. At 12 months, the proportion of patients who were seizure free, median percentage seizure reduction, proportion of responders, retention rate and proportion of patients with adverse events (AEs) were assessed. Analyses were also performed to identify any patient-, medication- and disease-related factors associated with a large clinical response or carry a risk for AEs. RESULTS: A total of 464 patients were included in the study with a retention rate of 60.6% at 1year. The mean number of prior AEDs was 7.8. The median percentage reduction in overall seizures was 33.3% (75% for secondary generalised seizures) after 1year, with 7.2% of patients achieving seizure freedom. Furthermore, patients on non-enzyme-inducing AEDs were more likely to achieve seizure freedom, and logistic regression revealed that patients aged ≥65 years, those with epilepsy due to a vascular aetiology and those who had received fewer prior AEDs showed a better clinical response to perampanel. A total of 62.9% of the patients experienced AEs at 12 months; dizziness, somnolence and irritability were the most frequent AEs. Patients with prior psychiatric comorbidities (hyperactivity and personality disorder) were more likely to experience psychiatric AEs with perampanel, and slower titration schedules were associated with less AEs overall. CONCLUSION: Perampanel, for the treatment of focal epilepsy in a real-world setting in a refractory population, over 1year, demonstrates a similar efficacy and safety profile to that observed in clinical trials. Our results have implications for the optimisation of perampanel use in a clinical setting.

Gene structure of the human mitochondrial outer membrane receptor Tom20 and evolutionary study of its family of processed pseudogenes.

The structure of the human gene encoding the mitochondrial outer membrane receptor Tom20 has been determined from overlapping clones obtained using PCR-based techniques. The 20kb human Tom20 gene (hTom20) consists of five exons separated by four introns. The 5' flanking region presents features common with other nuclear genes encoding mitochondrial proteins. Comparison with its homologs and putative homologs in other species has revealed common features in their TPR motifs and other relevant protein domains. Aspects concerning evolutionary origins of the family of processed pseudogenes of hTom20 are also discussed.

[Gm1 gangliosidosis types 1 and 2 (author's transl)]. / Gangliosidosis Gm1 tipo 1 y tipo 2.

Two cases of gangliosidosis due to aggregates of Gm1 are described. The first patient was a female infant with noticeable retardation in psychomotor development, coarse facies, hepatomegaly, and X-rays showing skeletal anomalies in the large bones, vertebral column, cranium and ribs. She died at the age of 10 months of a septic condition. The second patient was a male infant; deterioration in psychomotor development was first noticed 8 months after birth and this progressed slowly to arrive at a vegetative state with convulsions and myoclonus. The child died at the age of 4 years. There were no signs of enlargement of visceral organs but a cherry red stain was observed in the ophthalmologic examination. In the first case, necropsy revealed the presence of a deposit substance in the histiocytes of the hepatic sinusoids, spleen, pancreas, thymus, septi and pulmonary alveoli, intestinal lamina propria, epithelial cells of the renal glomeruli, and in the neurons and glial cells of the brain. The same deposits were observed only in the neurons and glial cells in the second case. Ultrastructural examination showed the presence of typical cytoplasmic membranous bodies in the central nervous system of both patients. The beta-galactosidase activity in the urine of both patients during life was zero. There was a higher than normal total amount of gangliosides in brain tissue samples from both (1906.7 and 2459.9 NANA/g respectively) as compared with normal values (724.0). This increase was proportional to the rise in Gm1 ganglioside (76.8 and 89.6 percent molar respectively) as compared to control (27.0). These clinical, morphologic, and biochemical data characterize both types 1 and 2 of gangliosidosis due to Gm1 aggregates.

[Comments with respect to 2 patients with anti-Jo 1 antibodies]. / Comentarios a dos enfermos con anticuerpos anti-Jo 1.

Anti-Jo 1 antibodies define a subgroup of patients with polymyositis, which are characterized by the presence of extra-muscular involvement as pulmonary fibrosis, although Raynaud's phenomena, arthritis, tenosynovitis, pleuritis and pericarditis may also be present. Given the fact that extra-muscular signs may precede the clinical diagnosis of polymyositis, as in the two cases that we present here, these antibodies may help us to diagnose the disease before the onset of myositis.

Long-term safety and efficacy of eslicarbazepine acetate in patients with focal seizures: results of the 1-year ESLIBASE retrospective study.

BACKGROUND: Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED) licensed as adjunctive therapy in adults with partial-onset or focal seizures. OBJECTIVE: To evaluate in a clinical practice setting the long-term efficacy and safety of ESL in patients with focal seizures. METHODS: ESLIBASE was a retrospective study that included all patients with focal seizures who started ESL between January 2010 and July 2012 at 12 hospitals. ESL was prescribed individually according to real-life practice. Efficacy and safety were evaluated over 1 year. Switching from carbamazepine (CBZ) and oxcarbazepine (OXC) was assessed. RESULTS: Three hundred and twenty-seven patients were included; 78% of patients were taking ≥2 other AEDs at baseline. Most (87%) began ESL because of poor seizure control and 13% because of adverse events (AEs) with CBZ or OXC. After 1 year, 237 patients (72.4%) remained on ESL. At 3, 6 and 12 months, the responder rate was 46.3%, 57.9%, and 52.5%, and 21.0%, 28.0%, and 25.3% of patients were seizure free. The responder rate significantly increased when ESL was combined with a non-sodium channel-targeting drug (non-SC drug) (66.7%) versus an SC drug (47.7%; p<0.001). At 12 months, 40.7% of patients had ≥1 AE; AEs led to treatment discontinuation in 16.2%. Dizziness, nausea, and somnolence were the most common AEs. The tolerability profile improved in >50% of the patients who switched from CBZ or OXC to ESL because of AEs. CONCLUSIONS: ESL was well tolerated and effective in a real-world setting over 1 year. Side-effect profile improved when OXC and CBZ recipients were switched to ESL.

Aneurisma de tronco arterial braquiocefálico asociado a erosión esternal. Reporte de un caso / Aneurisma de tronco arterial braquiocefálico associado a erosåo esternal. relato de um caso / Brachiocephalic arterial trunk aneurysm associated with sternal erosion. Report of a case

La aortitis sifilítica es frecuentemente asociada a aneurismas y/o enfermedad coronaria estenótica ostial, sin embargo este tipo de lesiones son raramente reportadas. Se reporta un caso deaneurisma de tronco arterial braquiocefálico con compresión y desplazamiento de estructuras vecinas,erosión esternal y su tratamiento...

A aortitis sifilítica é frequentemente associada a aneurisma e/ou enfermedade estenotica ostial, sem no entanto este tipo de lesão são raramente reportadas. Apresentamos um caso de aneurisma do tronco arterial braquiocefálico com compressão e deslocamento de estrcturas vizinhas, erosão esternal e seu tratamento...

Syphilitic aortitis is often associated with aneurysms and ostial stenotic coronary however such injuries are rarely reported. We report a case of brachiocephalic arterial trunk aneurysm with compression and displacement of neighboring structures, sternal erosion and its treatment...

The cerebral cortex of the new-born guinea pig. A quantitative Golgi study of the layer V pyramidal cell.

Quantitative studies have been performed in pyramidal cells (layer V) of the guinea pig's cerebral cortex when the animal were still-born and then not influenced by external sensorial stimuli nor by environment experience. Results related to basal ramifications of the pyramidal cells are similar to those reported in other species. Dendritic spines showed an increased in density along the length of the apical dendrites in a logarithmic regression. A similar pattern of distribution of dendritic spines along the apical dendrite was observed in a given animal, but interindividual variability was demonstrated.

Effects of prenatal exposure to ethanol on the maturation of the pyramidal neurons in the cerebral cortex of the guinea-pig: a quantitative Golgi study.

The effects of chronic ethanol consumption during gestation on the development of layer V pyramidal cells was studied quantitatively in the somatosensory cerebral cortex of the newborn guinea-pig. The spread of the basilar dendritic arborizations and counts of dendritic spines on the apical dendrite of neurons that had been processed with the rapid Golgi method were compared with those found in age-matched controls receiving an isocaloric diet without alcohol. There were significant differences in the number of primary basilar dendrites (P less than 0.05) and dendritic ramifications at a distance of 25 micron from the soma (P less than 0.01) between the alcohol-exposed and control animals. There also were significant differences in the number of dendritic spines on the apical dendrite (P less than 0.001). This experimental model further illustrates developmental anomalies in the cerebral cortex following prenatal ethanol exposure.

[Tick-borne recurrent fever. Description of 5 cases]. / Fiebre recurrente transmitida por garrapatas. Descripción de 5 casos.

BACKGROUND: Tick-borne relapsing fever (FRGT) is a worldwide zoonosis. The disease is caused by spirochetes of the genus Borrelia, and is transmitted to man by ticks of the genus Ornithodoros (O. erraticus in Spain). METHODS: 5 FRTG cases attended in our hospital in a 2 years period are described. Diagnosis was established in all cases by demonstration of borreliae in peripheral blood. Three Borrelia strains were isolated from blood of 3 of our patients and they are maintained by passages through mice. RESULTS: High fever, tachycardia and headache were noted in all cases accompanied in 2 of them by hepatosplenomegaly. Three of the patients complained of arthromyalgias or lumbar myalgia. Treatment with doxycicline was curative in all of them. CONCLUSIONS: FRGT incidence in our country is probably underestimated due to the low suspicion of the disease and the specificity of the clinical symptoms. The isolement of the causative Borrelia strain will allow the development of more specific serological tests necessary to establish the prevalence of this disease as well to assess its implication in chronic diseases, as is observed in other borreliosis (i.e. Lyme disease), that might be missed at this moment.

Cisplatin alone or in combination with adriamycin in the treatment of patients with head and neck cancer relapsed after radiotherapy and/or surgery.

37 evaluable patients with relapsed head and neck cancer received as treatment Cisplatin alone (18 patients) or Cisplatin + Adriamycin (19 patients). Both regimens consisted of three-weeks-interval courses. Cisplatin was administered at a dose of 100 mg/m2 as an i.v. infusion with prehydration, posthydration, mannitol and furosemide. Cisplatin + Adriamycin combination was administered at doses of 50 mg/m2 Cisplatin and 50 mg/m2 Adriamycin, both drugs the same day. Clinical toxicity was mild with both regimens. Overall hematologic toxicity was moderate but it was severe with regard to red cells. Some cases of renal toxicity were observed with Cisplatin regimen while no case was noticed with Cisplatin + Adriamycin combination. An overall response rate of 44% (4 CR + 4 PR) was achieved with Cisplatin protocol. The mean duration of response was 5,5 months. An overall response rate of 53% (3 CR + 7 PR) was achieved with Cisplatin + Adriamycin protocol. The mean duration of response was 2,75 months.

Cribaje clínico del adolescente obeso sospechoso de Shas / No disponible

INTRODUCCIÓN. Obesidad y las alteraciones del sueño son situaciones cada vez más frecuentes. Los objetivos de este estudio de casos y controles son comprobar si los niños obesos de nuestro medio tienen un mayor riesgo de presentar trastornos respiratorios durante el sueño, si existe correlación de la sospecha clínica con datos polisomnográficos y encontrar claves clínicas sencillas que permitan realizar un cribado de sospecha de estos problemas en asistencia primaria. MATERIAL Y MÉTODOS. Se estudiaron 51 niños seleccionados de manera consecutiva según orden de asistencia a consulta y que presentaban un índice de masa corporal (IMC) superior al percentil 85 y se compararon con 39 niños no obesos con IMC percentil menor 85 reclutados de manera consecutiva, de semejante edad y distribución por sexos que acudían a controles de salud. Se valoró el tamaño amigdalar e istmo velofaringeo radiológicamente. En los que cumplían los criterios clínicos de alteración respiratoria durante el sueño se realizó polisomnografía ambulatoria. RESULTADOS. Los datos clínicos seleccionados muestran una alta especificidad (85.71;CI 95%: 59.78- 111.64) y un alto valor predictivo positivo (96.30;CI 95%: 89.18-103.42) con la presencia de trastornos respiratorios durante el sueño demostrados en la polisomnografía. La presencia de hipertrofia amigdalar junto con estrechamiento del velo faringeo tienen una alta especificad ante la presencia de trastornos respiratorios durante el sueño. CONCLUSIÓN. El tamaño amigdalar mayor o igual a 3 junto con la obstrucción de la vía aérea superior tiene un alto valor de sospecha clínica de padecer un SDB en preadolescentes obesos y puede ser utilizado como un cribado clínico sencillo y rápido (AU)

INTRODUCTION. Obesity and sleep problems are situations increasingly frequent. The aims are to verify if the children with overweight/obesity have a major risk of presenting sleep respiratory disorders, if there exists correlation of the clinical suspicion with polisomnographic information and to find key simple clinics that allow to fulfill the screening of suspicion of these problems in primary care. MATERIALAND METHODS. There were studied 51 children selected of a consecutive way according to order of assistance to consultation and that had an index of corporal mass bigger that 85 percentile and there compared with 39 children with index of corporal mass minor percentile 85 recruited ones of a consecutive way, of similar age and distribution for sexes that were coming to controls of health. The tonsil size was clinical valued and the pharyngeal isthmus by RX. In those who were fulfilling the clinical criteria of sleep respiratory disorders was realized an ambulatory polysomnography. RESULTS. The clinical selected information shows a high specificity (85.71;CI 95%: 59.78- 111.64) and a positive predictive value of 96.30 (CI 95%: 89.18-103.42) with the presence of sleep respiratory disorders in the polysomnography. The presence of hypertrophic tonsils (>3) together with tightening of the pharyngeal istmus they have a discharge specify (80.00;CI 95%: 44.94-115.06) and a positive predictive value of 95.65 (CI 95%: 87.31-103.99) for the presence of sleep respiratory disorders. CONCLUSIONS. The size tonsils bigger or equal to 3 together with the obstruction of the top airway has a high value of clinical suspicion to endure a sleep disorders breathing in preadolescents with overweight and can be used like sifted clinical simply and rapidly (AU)

Estudos da estabilidade da secreçäo mucóide / Stability studies of mucus secretion

O objetivo do trabalho, é a determinaçäo de parâmetros definitórios do modelo de comportamento reológico da secreçäo mucóide das expectoraçöes, analisando as variaçöes produzidas em doentes tratadas ou näo como fármacos mucolíticos. Finalmente, é estudada a estabilidade da secreçäo mucóide frente a uma açäo de fricçäo repetitiva, definido o parâmetro de caracterizaçäo (coeficiente de perda logarítmica de viscosidade por ciclo), verificando, desta forma, sua estabilidade

Estudos reológicos realizados no líquido pleural com elevada concentraçäo de hémacias / Rheological studies of pleural secretion with high red cell concentration

O líquido pleural procedente de pacientes portadores de determinadas patologias apresenta uma concentraçäo elevada de hemácias, com valortes superiores a 5.000-6.000 hemácias/ml, valores mínimos necessários para obter uma coloraçäo sanguinolenta da soluçäo extraída. Esta causa obrigará posteriores realizaçöes, neste caso de tipo viscosimétrico, sobre amostras adicionadas de anticoagulante. Por causa disto, é necessário a análise cuidadosa das modificaçöes que o anticoagulante (heparina) exerce sobre os valores obtidos dos parâmetros definitórios do modelo de comportamento reológico do líquido pleural. Procedeu-se, pois, a caracterizaçäo reológica das amostras com elevada concentraçäo hemática, passando, a partir dos valores experimentais obtidos, a realizaçäo do teste estimativo de Darmois, comparativo de populaçöes de médias normais conhecidas