Enfermedad neurológica asociada al gen KIF1A: correlación genotipo/fenotipo / KIF1A gene-associated neurological disease: the correlation between genotype and phenotype

Introducción: La encefalopatía KIF1A-associated-neurological-disorder (KAND) es un grupo de patologías neurodegenerativas progresivas de diversa gravedad ocasionadas por mutaciones en el gen KIF1A (kinesin family member 1A) situado en el cromosoma 2q37.3. Dicho gen codifica una proteína de la familia de las cinesinas 3 que participa en el transporte anterógrado de las vesículas presinápticas dependientes del trifosfato de adenosina a través de microtúbulos neuronales. Casos clínicos: Se describen cuatro pacientes, con edades entre 1 y 13 años, con mediana de inicio de los síntomas de cinco meses (rango intercuartílico: 0-11 meses), lo que supone una prevalencia aproximada de 1 de cada 64.000 menores de 14 años para nuestra población pediátrica. Clínicamente, destacaron discapacidad intelectual, hipotonía axial y paraparesia espástica en 4/4, y síntomas cerebelosos en 2/4. Otras manifestaciones fueron incontinencia urinaria, polineuropatía sensitivomotora y alteración conductual. Destaca, en el caso 2, la alteración en el videoelectroencefalograma, que mostraba epilepsia focal con generalización secundaria y focalidad paroxística occipitoparietal posterior derecha con transmisión contralateral. También mostraba crisis oculógiras en supraversión instantáneas pluricotidianas sin correlato electroencefalográfico. Conclusiones: En nuestra serie, la encefalopatía KAND, fenotipo trastorno neurodegenerativo con retraso global del desarrollo, de la marcha y espasticidad progresiva de los miembros inferiores, atrofia cerebelosa y/o afectación de la corteza visual, fue predominante, y en uno de los casos asoció polineuropatía sensitivomotora. La mutación de novo missense fue más frecuente y en tres casos es la primera descripción conocida. Un caso mostraba epilepsia focal y crisis oculógiras no epilépticas.(AU)

Introduction: KIF1A-associated-neurological-disorder (KAND) encephalopathy is a group of progressive neurodegenerative pathologies of varying severity caused by mutations in the KIF1A gene (Kinesin family member 1A) located on chromosome 2q37.3. This gene encodes a protein of the kinesin-3 family that participates in the ATP-dependent anterograde transport of presynaptic vesicles through neuronal microtubules. Case report: Four patients are described, aged 1-13 years, with a median onset of symptoms of 5 months (IQR 0-11 months), which represents an approximate prevalence of 1 per 64,000 children under 14 years of age for our pediatric population. Clinically, intellectual disability (ID), axial hypotonia and spastic paraparesis stood out in 4/4 and cerebellar symptoms in 2/4. Other manifestations were urinary incontinence, sensory-motor polyneuropathy, and behavioral alteration. In case 2, the alteration in the video-EEG stands out, which showed focal epilepsy with secondary generalization and right posterior occipito-parietal paroxysmal focality with contralateral transmission. She also showed instantaneous pluricotidian supraversion oculogyric seizures without EEG correlates. Conclusions: In our series, KAND encephalopathy had a predominant neurodegenerative disorder phenotype with global developmental delay, gait delay, and progressive spasticity of the lower limbs, cerebellar atrophy, and/or involvement of the visual cortex, which in one case was associated with sensory-motor polyneuropathy. The de novo missense mutation was more frequent and in three cases it is the first known description. One case showed focal epilepsy and nonepileptic oculogyric seizures.(AU)

[KIF1A gene-associated neurological disease: the correlation between genotype and phenotype]. / Enfermedad neurológica asociada al gen KIF1A: correlación genotipo/fenotipo.

INTRODUCTION: KIF1A-associated-neurological-disorder (KAND) encephalopathy is a group of progressive neurodegenerative pathologies of varying severity caused by mutations in the KIF1A gene (Kinesin family member 1A) located on chromosome 2q37.3. This gene encodes a protein of the kinesin-3 family that participates in the ATP-dependent anterograde transport of presynaptic vesicles through neuronal microtubules. CASE REPORT: Four patients are described, aged 1-13 years, with a median onset of symptoms of 5 months (IQR 0-11 months), which represents an approximate prevalence of 1 per 64,000 children under 14 years of age for our pediatric population. Clinically, intellectual disability (ID), axial hypotonia and spastic paraparesis stood out in 4/4 and cerebellar symptoms in 2/4. Other manifestations were urinary incontinence, sensory-motor polyneuropathy, and behavioral alteration. In case 2, the alteration in the video-EEG stands out, which showed focal epilepsy with secondary generalization and right posterior occipito-parietal paroxysmal focality with contralateral transmission. She also showed instantaneous pluricotidian supraversion oculogyric seizures without EEG correlates. CONCLUSIONS: In our series, KAND encephalopathy had a predominant neurodegenerative disorder phenotype with global developmental delay, gait delay, and progressive spasticity of the lower limbs, cerebellar atrophy, and/or involvement of the visual cortex, which in one case was associated with sensory-motor polyneuropathy. The de novo missense mutation was more frequent and in three cases it is the first known description. One case showed focal epilepsy and nonepileptic oculogyric seizures.

TITLE: Enfermedad neurológica asociada al gen KIF1A: correlación genotipo/fenotipo.Introducción. La encefalopatía KIF1A-associated-neurological-disorder (KAND) es un grupo de patologías neurodegenerativas progresivas de diversa gravedad ocasionadas por mutaciones en el gen KIF1A (kinesin family member 1A) situado en el cromosoma 2q37.3. Dicho gen codifica una proteína de la familia de las cinesinas 3 que participa en el transporte anterógrado de las vesículas presinápticas dependientes del trifosfato de adenosina a través de microtúbulos neuronales. Casos clínicos. Se describen cuatro pacientes, con edades entre 1 y 13 años, con mediana de inicio de los síntomas de cinco meses (rango intercuartílico: 0-11 meses), lo que supone una prevalencia aproximada de 1 de cada 64.000 menores de 14 años para nuestra población pediátrica. Clínicamente, destacaron discapacidad intelectual, hipotonía axial y paraparesia espástica en 4/4, y síntomas cerebelosos en 2/4. Otras manifestaciones fueron incontinencia urinaria, polineuropatía sensitivomotora y alteración conductual. Destaca, en el caso 2, la alteración en el videoelectroencefalograma, que mostraba epilepsia focal con generalización secundaria y focalidad paroxística occipitoparietal posterior derecha con transmisión contralateral. También mostraba crisis oculógiras en supraversión instantáneas pluricotidianas sin correlato electroencefalográfico. Conclusiones. En nuestra serie, la encefalopatía KAND, fenotipo trastorno neurodegenerativo con retraso global del desarrollo, de la marcha y espasticidad progresiva de los miembros inferiores, atrofia cerebelosa y/o afectación de la corteza visual, fue predominante, y en uno de los casos asoció polineuropatía sensitivomotora. La mutación de novo missense fue más frecuente y en tres casos es la primera descripción conocida. Un caso mostraba epilepsia focal y crisis oculógiras no epilépticas.

Cinacalcet en pacientes en diálisis peritoneal con hiperparatiroidismo moderado-severoresistentes a tratamiento convencional. Estudio prospectivo a un año / No disponible

Objetivos: Estudiar la eficacia de Cinacalcet(R) en el cumplimiento de las recomendaciones K/DOQI en pacientes en diálisis peritoneal (DP) y estimar el tiempo necesario para alcanzarlos. Métodos: Estudio observacional prospectivo de cohorte, con pacientes con hiperparatiroidismo-HPTH moderado severo(PTH > 500 pg/ml) con más de 4 meses en DP resistentes a tratamiento convencional con dieta, quelantes y vitamina D. Los objetivos óptimos son los recomendados por las Guías NKF-K/DOQI para ERC-5D y para el análisis de objetivos subóptimos se utilizan las referencias de PTH< 350 pg/ml.; fósforo < 6 mg/dl o calcio < 10,4 mg/dl (siempre ue simultáneamente CaxP < 55 mg2/dl2).Resultados: Al inicio del tratamiento con Cinacalcet(R) los 18 pacientes llevaban 15,56 meses (DE 0,78) en DP, todos tenían una PTH > 500 pg/ml, y ninguno cumplía los objetivos K/DOQI ni los subóptimos propuestos. El seguimiento medio en tratamiento con Cinacalcet(R) fue de 12 meses. El porcentaje de pacientes con PTH < 350 pg/ml fue de 66,7%a los 3 meses 60% a los 6 y 100% al año. A los tres meses el 33,3% cumplen todos los objetivos subóptimos, a los 6 meses el 33,3% y al año el 66,7%. El tiempo medio necesario para alcanzar un valor de PTH en rango fue de 2,33meses IC al 95% [1,35-3,32] y para alcanzar todos los objetivos óptimos de 16,94 meses [11,38-22,5]. La tolerancia a la medicación ha sido buena, no se suspendió Cinacalcet(R) en ningún caso y sólo en uno se redujo la dosis por efectos secundarios. Conclusión: La utilización de Cinacalcet® en pacientes en DP con HPTH resistente a tratamiento convencional ha resultado eficaz y segura y ha permitido mejorar el cumplimiento de objetivos de las guías (AU)

Background: Cinacalcet(R) has improved the management of hyperparathiroidism(HPTH) in hemodialysis. To our knowledge there are no specific studies on peritoneal dialysis (PD).Aim: The aim of the present study was to evaluate the efficacy of Cinacalcet(R) on the achievement of optimal and suboptimal targets on treatment of hyperparathiroidism (HPTH) in PD patients. As secondary objectives we have studied the safety of treatment and estimate the mean time to reach these targets, and evaluate economic cost. Methods: Eighteen patients undergoing more than 4 months on PD with a severe HPTH (PTH > 500 pg/ml) resistant to conventional treatment with diet, chelants and vitamin D were included in this prospective open-label study. We have used the targets of K/DOQITM-clinical guidelines as optimal target. We have selected as suboptimal targets: PTH < 350 pg/ml, phosphorus< 6 mg/dl and calcium < 10.4 mg/dl (only when simultaneous CaxP was under 55 mg2/dl2). Oral Cinacalcet(R) was given with main meal in a single daily start dose of 30 mg and titrated thereafter monthly. We considered the first value on target as an event and used a Kaplan-Meyer survival analysis to estimate mean time to reach target. Results: On inclusion all patients have at least two previous PTH values over 500 pg/ml, PTH mean 695.3 (SD 96) and they were on PD with an appropriate efficacy during a mean of15.56 months (SD 0.78). Mean follow-up time under Cinacalcet(R) treatment was 12 months. The percentage of patients with a PTH under 350 pg/ml was 66.7% on month 3, 60% on month 6 and 100% after 1 year. The percentage of patients that reach an aggregate of all suboptimal targets (PTH < 350 pg/ml, phosphorus < 6 mg/dl and calcium < 10.4 mg/dl (only when simultaneous CaxP was under 55 mg2/dl2). Oral Cinacalcet(R) was given with main meal in a single daily start dose of 30 mg and titrated thereafter monthly. We considered the first value on target as an event and used a Kaplan-Meyer survival analysis to estimate mean time to reach target. Results: On inclusion all patients have at least two previous PTH values over 500 pg/ml, PTH mean 695.3 (SD 96) and they were on PD with an appropriate efficacy during a mean of 15.56 months (SD 0.78). Mean follow-up time under Cinacalcet(R) treatment was 12 months. The percentage of patients with a PTH under 350 pg/ml was 66.7% on month 3, 60% on month 6 and 100% after 1 year. The percentage of patients that reach an aggregate of all suboptimal targets (PTH < 350 pg/ml and calcium < 10.4 mg/dl and phosphorus < 6 mg/dl and CaxP < 55 mg2/dl2) was 33.3% on month 6 and 66.7% after 1 year. The mean time to reach PTH target was 2.33 months with a 95% confident interval [1,35-3,32] and to reach the aggregate of all target was 16.94 months [11,38-22,5]. Cinacalcet ® has been well tolerated, we reduced the dose in a single patient due to secondary effects, but treatment was not discontinued in any case. Conclussion: In summary the addition of Cinacalcet(R) to conventional treatment in PD patients with resistant HPTH has improved the achievement of targets, and has been reasonably safe in our patients (AU)

[Cinacalcet in patients on peritoneal dialysis with moderate to severe hyperparathyroidism resistant to conventional treatment, a one-year, prospective study]. / Cinacalcet en pacientes en diálisis peritoneal con hiperparatiroidismo moderado-severo resistentes a tratamiento convencional. Estudio prospectivo a un año.

BACKGROUND: Cinacalcet has improved the management of hyperparathiroidism (HPTH) in hemodialysis. To our knowledge there are no specific studies on peritoneal dialysis (PD). AIM: The aim of the present study was to evaluate the efficacy of Cinacalcet on the achievement of optimal and suboptimal targets on treatment of hyperparathiroidism (HPTH) in PD patients. As secondary objectives we have studied the safety of treatment and estimate the mean time to reach these targets, and evaluate economic cost. METHODS: Eighteen patients undergoing more than 4 months on PD with a severe HPTH (PTH > 500 pg/ml) resistant to conventional treatment with diet, chelants and vitamin D were included in this prospective open-label study. We have used the targets of K/DOQITM-clinical guidelines as optimal target. We have selected as suboptimal targets: PTH < 350 pg/ml, phosphorus < 6 mg/dl and calcium < 10.4 mg/dl (only when simultaneous CaxP was under 55 mg2/dl2). Oral Cinacalcet was given with main meal in a single daily start dose of 30 mg and titrated thereafter monthly. We considered the first value on target as an event and used a Kaplan-Meyer survival analysis to estimate mean time to reach target. RESULTS: On inclusion all patients have at least two previous PTH values over 500 pg/ml, PTH mean 695,3 (SD 96) and they were on PD with an appropriate efficacy during a mean of 15.56 months (SD 0.78). Mean follow-up time under Cinacalcet treatment was 12 months. The percentage of patients with a PTH under 350 pg/ml was 66,7% on month 3, 60% on month 6 and 100% after 1 year. The percentage of patients that reach an aggregate of all suboptimal targets (PTH< 350 pg/ml and calcium < 10.4 mg/dl and phosphorus< 6 mg/dl and CaxP < 55 mg2/dl2) was 33.3% on month 6 and 66.7% after 1 year. The mean time to reach PTH target was 2.33 months with a 95% confident interval [1.35-3.32] and to reach the aggregate of all target was 16.94 months [11.38-22.5]. Cinacalcet has been well tolerated, we reduced the dose in a single patient due to secondary effects, but treatment was not discontinued in any case. CONCLUSION: In summary the addition of Cinacalcet to conventional treatment in PD patients with resistant HPTH has improved the achievement of targets, and has been reasonably safe in our patients.

Streptococo agalactiae y taponamiento pericárdico / Streptococcus agalactiae and pericardial tamponade

No disponible

[Theophylline semi-solid matrices containing polyethyleneglycols. 3--Mechanism of release]. / Matrices semi-solides de théophylline à base de polyéthyleneglycols. 3--Mécanisme de libération.

Some rheologic mesures made on a PEG range ranking from PEG 300 to PEG 6000 and containing, as a theophylline plot indicate an expected result: the viscosity increases with the molecular mass of the polymer. These same measures made on a binary mixture of PEG composed of 95% PEG 300, liquid, and 5% of solid, thickening, make appear the peculiarity of the binary mixtures of PEG: the viscosity of the binary mixture of PEG is higher than the one of the solid PEG. This "paradoxical" viscosity results, apparently, on one side from the concomitant translation and opposed of the respective points of vitrous transition of the vehicle (liquid PEG) and of the thickening (solid PEG); and on the other side, of the different solidifications of the chains of different polymers forming the binary mixture.

Coma e insuficiencia respiratoria tras fractura de fémur y tibia / Coma and respiratory insufficiency after fracture of femur and tibia

No disponible

Infarto de miocardio por anfetamina / Myocardial infarction by amphetamine abuse

No disponible

[Efficacy of an intervention in smoking cessation in patients with myocardial infarction]. / Eficacia de una intervención para dejar de fumar en pacientes con infarto de miocardio.

BACKGROUND: The aim of this study was to evaluate the efficacy of an structured intervention based on a medical advice versus to the ordinary anti-tobacco advice in patients with miocardial infarction who are attended in an Intensive Care Unit (ICU). PATIENTS AND METHODS: 90 patients were randomly selected to receive either the specific intervention (intervention group) or the ordinary advice (control group). The medical advice was given during the ICU hospitalization and during the second, the third and the fourth week. One year later the smoking habit was evaluated. RESULTS: After one year 26 patients of the intervention group and 31 patients of the control group had stopped smoking (RR = 0.88 [CI 95% RR] 0.57 to 1.37). CONCLUSIONS: The percentage of patients who stop smoking after a miocardial infarction is high. The structured medical counselling was not effective to reduce the number of smokers at one year.