RESUMEN
Resumen Los tumores cerebrales se caracterizan por su gran morbilidad y mortalidad. La gran mayoría corresponde a tumores secundarios (metástasis). Dentro de los tumores primarios del sistema nervioso central, los gliomas corresponden al 30% de éstos. En EEUU, entre el 2007-2011, se estima una incidencia aproximada de 21,4 casos por 100.000 habitantes. Los recientes avances en la comprensión molecular de la biología de estos tumores han permitido mejorar sustancialmente su clasificación, posibilitando realizar un mejor correlato con los desenlaces clínicos y el pronóstico. En esta línea, hoy en día es posible estratificar a los pacientes por riesgo y entregar tratamientos capaces de prolongar la sobrevida global entre 5-7 años, para los gliomas grado II y III. El presente consenso, elaborado por un panel multidisciplinario de expertos de diversas sociedades científicas chilenas y, por tanto, de todas las especialidades involucradas en el manejo médico-quirúrgico de las personas portadoras de gliomas cerebrales. A la luz de este nuevo conocimiento desarrollado al alero de la oncología molecular, esta propuesta ofrece un insumo de utilidad clínica real, que, articulado a una revisión actualizada en relación con el tratamiento y seguimiento de estos pacientes, permite entender la relevancia de estos biomarcadores en el manejo de precisión de la enfermedad. Cabe señalar que, este manuscrito emerge de la misma fuerza de trabajo, que elaboró el Protocolo Clínico de Gliomas del Adulto 2019, publicado por el Ministerio de Salud, y que ha diferencia de esta, que ofrece los detalles clínicos-operativos, como flujogramas y dosis, nuestra revisión intenta relevar los avances imagenológicos y moleculares y como estos impactan en el manejo actual de la enfermedad.
Brain tumors are characterized by high morbidity and mortality. The vast majority correspond to secondary tumors (metastasis). On the other hand, within the primary tumors of the central nervous system, gliomas correspond to 30% of these. In the US, between 2007-2011, an approximate incidence of 21.4 cases per 100,000 inhabitants was estimated. Recent advances in the molecular understanding of the biology of these tumors have made it possible to substantially improve their classification, allowing a better correlation with clinical outcomes and prognosis. Along these lines, today, it is possible to stratify patients by risk and deliver treatments capable of prolonging global survival between 5-7 years, for grade II and III gliomas. The present consensus, prepared by a multidisciplinary panel of experts from various Chilean scientific societies and, therefore, from all the specialties involved in the medical and surgical therapy. Enlightened from the molecular oncology, this proposal offers an input of clinical utility, which, together with an updated review in relation to the treatment and follow-up of these patients, allows us to understand the relevance of these biomarkers in precision disease management. It should be noted that this manuscript emerges from the same work force, which prepared the Clinical Protocol for Adult Gliomas 2019, published by the Ministry of Health, and that differs from it, which offers clinical-operative details, such as flowcharts and dose, our review attempts to reveal imaging and molecular advances and how they impact the current management of the disease.
Asunto(s)
Humanos , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Glioma/diagnóstico , Glioma/terapia , Chile , ConsensoRESUMEN
The African most prevalent tropical disease after malaria is schistosomiasis and this disease in the developing countries is a massive socio-economic and public health burden. The disease also caused over 200,000 deaths. The development and design of new and novel antischistosomal drugs is now very important, as there are no vaccines currently and there is only one drug at the moment for the treatment of schistosomiasis. In this article, 6-gingerol was docked against the Schistosoma mansoni phosphofructokinase and the docking result was compared to those obtained from the docking of its modified analogues against the same enzyme. The chemical structure of 6-gingerol was obtained from the PubChem database while the modified analogues were designed using the ChemAxon software. The molecular docking procedure was carried out with the aid of the AutoDock Vina software while polar interactions which were eventually used in predicting the amino acid residues at the Schistosoma mansoni phosphofructokinase active site were visualized using the Pymol software. The Schistosoma mansoni phosphofructokinase 3D crystallized structure was modeled using the Swiss Model server. The molecular docking result showed that the modifications made on 6-gingerol had a positive effect on the binding energy of the compound to the enzyme active site as an appreciable increase was observed. 6-Gingerol and its modified analogues also violated none of the Lipinski's rule with suggests that the experimental compounds are drug-like. The C2H5 analogue of 6 gingerol was selected as the ideal therapeutic agent based on the pharmacokinetics study and the exhibited binding energy(AU)
La enfermedad tropical con más prevalencia en África después de la malaria es la esquistosomiasis; en los países en vías de desarrollo constituye una carga socio-económica y de salud pública enorme. La enfermedad ha ocasionado más de 200.000 muertes anuales. El desarrollo y diseño de nuevas y novedosas drogas antiesquistosomales es muy importante, ya que actualmente no existe vacuna disponible y solo hay una sola droga licenciada para su tratamiento. En esta investigación, el compuesto 6-gingerol se acopló a la enzima fosfofructoquinasa de Schistosoma mansoni y se comparó con los resultados obtenidos a partir de las interacciones de sus análogos modificados a la misma enzima. La estructura química del 6-gingerol se obtuvo de la base de datos PubChem, mientras que los análogos modificados se diseñaron utilizando el software ChemAxon. El procedimiento de acoplamiento molecular se llevó a cabo con la ayuda del software AutoDockVina, mientras las interacciones polares eventualmente utilizadas para predecir los residuos de aminoácidos en el sitio activo de la enzima fosfofructoquinasa de Schistosoma mansoni se visualizaron empleando el software Pymol. La estructura cristalizada tridimensional de la enzima fosfofructoquinasa de Schistosoma mansoni se modeló utilizando el programa Swiss Model. Se demostró que las modificaciones realizadas en el 6-gingerol tuvieron un efecto positivo en la energía de unión del compuesto al sitio activo de la enzima, tras observarse un aumento apreciable de dicha energía. El compuesto 6-Gingerol y sus análogos modificados tampoco violaron ninguna de las reglas de Lipinski, lo que sugiere que estos compuestos experimentales tienen propiedades similares a los medicamentos. El análogo C2H5 de 6-gingerol se seleccionó como el agente terapéutico ideal, basados en el estudio de farmacocinética y la energía de enlace demostrada(AU)
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Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/epidemiología , Farmacocinética , Fosfofructoquinasas/uso terapéutico , ÁfricaRESUMEN
Introduction: Cerebellar mutism syndrome refers to the muteness (lack of speech) that follows lesions of the cerebellum. Its characterized by a late onset, limited duration, and in some cases long-term language sequelae. Its pathogenesis it s not clear yet, but it has been attributed a role to a damage of the dentate nucleus and of the dento-rubro-thalamic tract. Objectives: Identify potential risk factors (clinical or anatomical) to predict the onset of cerebellar mutism after posterior fossa surgery Compare, using MRI analysis and DTI tractography, the integrity of the dento-rubro-thalamic tract in patients with and without cerebellar mutism. Methods: Prospective follow up study of patients operated of posterior fossa tumors between November 2012 and 2013. We performed a study with DTI of the dento rubro thalamic tract in pacients with and without postoperative mutism. Results: 53 patients under the diagnosis of posterior fossa tumor underwent surgical resection. 5 pacients presented postoperative mutism (9,4 percent). There was a significant association between postoperative medulloblastoma diagnosis and postoperative mutism. Tumor volume was not significant. The volume of left and right dento rubro thalamic tract were significantly lower in patients with cerebellar mutism. The fractional anisotropy of the right superior cerebellar peduncle was also lower in patients with postoperative mutism. Conclusions: The postoperative cerebellar mutism is a relevant complication after a posterior fossa surgery. Our study supports the role of dento rubro thalamic tract damage in the pathogenesis of this syndrome. Special care must be taken during surgery to prevent damage to this tract.
Introducción: El síndrome mutismo cerebeloso consiste en falta del habla posterior a lesiones del cerebelo. Se caracteriza por inicio tardío, duración limitada, y ocasionalmente secuelas lingüísticas. Su patogenia no está clara, pero se ha atribuido un rol a daños en el núcleo dentado y en la vía dento-rubro-talámica. Objetivos: Identificar posibles factores de riesgo (clínicos o anatómicos) asociados a la aparición de mutismo cerebeloso después de una cirugía de fosa posterior. Comparar, mediante un análisis de resonancia magnética (IRM) y tractografía por tensor de difusión (DTI), la integridad de la vía dento-rubro-talámica en pacientes con y sin mutismo cerebeloso. Métodos: Estudio prospectivo de pacientes operados por tumores de fosa posterior entre noviembre de 2012 y 2013. Se analizó con DTI la vía dento-rubro-talámica en pacientes con y sin mutismo postoperatorio. Se comparó la volumetría del tracto en ambas cohortes. Resultados: Cincuenta y tres pacientes con diagnóstico de tumor de fosa posterior fueron sometidos a cirugía de exéresis. Cinco pacientes presentaron mutismo postoperatorio (9,4 por ciento). Hubo una asociación significativa entre el diagnóstico de meduloblastoma y mutismo postoperatorio. El volumen tumoral no fue significativo. El volumen de la vía dento-rubro-talámica fue significativamente menor en pacientes con mutismo, en forma bilateral, así como la anisotropía fraccional del pedúnculo cerebeloso derecho. Conclusiones: El mutismo cerebeloso es una complicación relevante después de una cirugía de fosa posterior. Nuestro estudio apoya el papel del daño de la vía dento-rubro-talámica en la patogénesis de este síndrome. Se debe tener especial cuidado durante la cirugía para prevenir daños al núcleo dentado.
Asunto(s)
Humanos , Masculino , Adolescente , Femenino , Lactante , Preescolar , Niño , Cerebelo/patología , Complicaciones Posoperatorias/diagnóstico , Mutismo/diagnóstico , Mutismo/etiología , Neoplasias Infratentoriales/cirugía , Imagen de Difusión Tensora , Imagen por Resonancia Magnética , Estudios Prospectivos , Factores de RiesgoRESUMEN
El objetivo de este trabajo es dar a conocer los resultados, a mediano plazo, de una cohorte de mujeres con Síndrome de Vejiga Hiperactiva (SVH) tratadas mediante un protocolo de rehabilitación de piso pélvico en una consulta kinésica particular. Se intervino una cohorte de 20 mujeres derivadas a la Unidad de Piso Pélvico del Centro Médico IDG por diagnóstico de SVH entre marzo de 2010 y marzo de 2012. La evaluaciones se realizaron al momento del enrolamiento, al finalizar la intervención y luego de 5 a 12 meses de concluida la intervención. Las variables evaluadas fueron: frecuencia miccional diurna y nocturna, urgencia miccional, fuerza muscular de piso pélvico y calidad de vida. La intervención consistió en 10 sesiones de 45 minutos, 2 veces por semana. Se aplicó un protocolo que comprende: entrena- miento muscular de piso pélvico y biofeedback, neuromodulación tibial posterior y reeducación vesical mediante calendario miccional y láminas educativas. La mediana de edad de las pacientes fue 54.5 años y la media de seguimiento fue 11.77 meses. Completaron las 10 sesiones programadas el 80 por ciento de las pacientes. Existió una mejoría significativa entre el basal y el control inmediato a la intervención en las siguientes variables: incontinencia de esfuerzo, score de urgencia, frecuencia miccional diurna y nocturna, fuerza muscular y calidad de vida. Esta tendencia se mantiene al final del seguimiento para las variables frecuencia miccional diurna, frecuencia miccional nocturna y la calidad de vida. El único parámetro que mantuvo su significancia estadística en el seguimiento a mediano plazo fue la frecuencia miccional diurna. Esto no ocurrió con los parámetros frecuencia miccional nocturna y calidad de vida. La rehabilitación integral del piso pélvico es una herramienta eficiente en el tratamiento del SVH, mejorando significativamente parámetros como urgencia, frecuencia miccional diurna y nocturna, fuerza de los músculos elevadores del ano.
The aim of this paper is to present medium term results of a cohort of women with overactive bladder syndrome (SVH) treated with a protocol of pelvic floor rehabilitation in a private Kinesiology office. A cohort of 20 women referred to the Pelvic Floor unit of IDG Medical Center due to diagnosis of SVH between March 2010 and March 2012 was evaluated. The evaluations were performed at enrollment, at the end of intervention and 5-12 months after having completed the intervention. Evaluated variables were: daytime and nighttime urinary frequency, urinary urgency, pelvic floor muscle strength and quality of life. The intervention consisted of 10 sessions of 45 minutes, 2 times a week. Using muscular workout, pelvic floor biofeedback, posterior tibial neuromodulation and bladder voiding re-education through educational micturition calendar. The median age of patients was 54.5 years and the mean follow-up was 11.77 months. 80 percent of patients completed the 10 sessions as scheduled. There was a significant improvement between baseline and immediate intervention in the following control variables: stress incontinence, urgency score, daytime and nighttime urinary frequency, muscle strength and quality of life. This trend is maintained at follow-up variables for daytime frequency, nighttime frequency and quality of life. The only parameter that maintained its statistical significance in the midterm follow-up was daytime voiding frequency. This did not happen with the parameters nocturnal voiding frequency and quality of life. The comprehensive rehabilitation of the pelvic floor is an efficient tool in the treatment of SVH, significantly improving parameters such as urgency, daytime and nighttime urinary frequency, strength of the levator any muscles and quality of life.
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Humanos , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Diafragma Pélvico/fisiología , Vejiga Urinaria Hiperactiva/rehabilitación , Calidad de Vida , Terapia por EjercicioRESUMEN
Según la ICS, la primera línea de tratamiento para Incontinencia de Orina debería ser la rehabilitación kinésica de piso pélvico ya que se produce una mejoría de los síntomas hasta en un 85 por ciento de los casos. El objetivo de este trabajo fue describir los resultados de una cohorte de mujeres incontinentes tratadas con un protocolo de rehabilitación, comparando la técnica biofeedback manual versus biofeedback electromiográfico. Se analizó un total de 68 mujeres de 30 a 80 años de edad con diagnóstico médico de IU, derivadas a Rehabilitación kinésica de piso pélvico entre marzo de 2011 y marzo de 2012. Se generaron 2 grupos de intervención mediante muestreo dirigido. En el grupo 1 (G1) constó de 48 mujeres que recibieron el siguiente protocolo: biofeedback manual (BM), pauta de ejercicios en domicilio y neuro modulación de tibial posterior. El grupo 2 (G2) constó de 20 mujeres que fueron tratadas con biofeedback electromiográfico (BEM) y la misma pauta de ejercicios en domicilio y protocolo de neuro modulación de tibial posterior. Al evaluar los datos obtenidos no se objetivaron diferencias signi-ficativas entre ambos grupos previo a la intervención. En todos los casos y con ambas técnicas se objetivan mejorías significativas en cuanto a frecuencia miccional diurna / nocturna, numero de apósitos diurno / nocturno, cuantía de la fuga, fuerza muscular y calidad de vida. Sin embargo, se objetivo menor frecuencia de micción diurna al final del seguimiento con técnica BEM (mediana de 5, IC 95 por ciento 1.12 7) respecto al BM (mediana de 7, IC 95 por ciento 6-7) p= 0.0208. Conclusión: Ambas protocolos de rehabilitación kinésica del piso pélvico mostraron mejoría significativa en la calidad de vida y fuerza perineal, evidenciando una disminución en los episodios de incontinencia, urgencia y uso de apósitos. Por otra parte, la única diferencia significativa entre el protocolo de biofeedback electromiográfico y manual, fue que el primero mostró menor...
According to the ICS, the first line of treatment for urinary incontinence should be pelvic floor rehabilitation, as it shows an improvement of symptoms in 85 percent of cases. The aim of this study was to describe the results of a cohort of incontinent women treated with a rehabilitation protocol, comparing the techniques: Manual versus Electromyographic biofeedback. Material and methods: We analyzed a total of 68 women, 30- 80 years of age, with medical diagnosis of urinary incontinente referred to Pelvic Floor Rehabilitation between March 2011 and March 2012. 2 groups were generated by targeted intervention. Group 1 (G1) consisted of 48 women who received the following protocol: Manual biofeedback (BM), exercise regimen at home and posterior tibial neuromodulation. Group 2 (G2) consisted of 20 women who were treated with Electromyographic biofeedback (BEM) and the same pattern of exercise protocol and posterior tibial neuromodulation. The data obtained showed no signi¬ficant differences between the two groups before the intervention. In all cases and with both techniques are we objectified significant improvements in terms of urinary frequency day / night, number of pads day / night, amount of leakage, muscle strength and quality of life. However, we observed less daytime micturition frequency at follow- up with BEM technique (median 5, 95 percent CI 1.12 - 7) compared to BM (median of 7, 95 percent CI 6- 7) p = 0.0208. Both pelvic floor reahabilitation protocols showed significant improvement in quality of life and perineal strength, showing a decrease in incontinence episodes, urgency and use of pads. Moreover, the only signi¬ficant difference between electromyographic biofeedback protocol and manual biofeedback protocol, was that the daytime voiding frequency was lower in the ¬ first Group compared to the second.
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Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Diafragma Pélvico , Enfermedades Urológicas/rehabilitación , Modalidades de Fisioterapia , Incontinencia Urinaria/rehabilitaciónRESUMEN
La hidrocefalia es una complicación frecuente de la hemorragia subaracnoídea (HSA); se ha propuesto la fenestración de la lamina terminalis en el momento del clipaje aneurismático como un medio de facilitar la dinámica del flujo de líquido cefaloraquídeo (LCR) y de reducción de la incidencia de HCF dependiente de shunt. Realizamos un analisis retrospectivo para probar la hipótesis de que la fenestración de la lamina terminalis efectivamente reduce la incidencia de HCF dependiente de shunt y de complicaciones isquémicas en pacientes con hemorragia subaracnoídea aneurismática (grado de Fisher modificado III o IV). Las fichas clínicas de 145 pacientes con hemorragia subaracnoídea aneurismática fueron analizadas; 48 de estos pacientes recibieron tratamiento con coiling endovascular y 97 fueron tratados con clipaje microquirúrgico. De estos últimos, 9 pacientes fueron sometidos a fenestración de la lamina terminalis. En los 9 pacientes con fenestración de la lamina terminalis. No hubo ningún caso de HCF dependiente de shunt. En los 104 pacientes con HSA grado 3 o 4 en los cuales el aneurisma fue tratado pero la lamina terminalis no fue fenestrada, la incidencia de HCF dependiente de shunt fue de 5,3 por ciento; esta diferencia no fue estadísticamene significativa (p=0,378). Pese a que los resultados de este estudio no apoyan la real efectividad de la FLT en la reducción de la incidencia de HCF dependiente de shunt, la tasa de complicaciones isquémicas o la mortalidad a 6 meses en pacientes con HAS aneurismática, observamos una tendencia en el grupo con FLT a mostrar una menor incidencia de HCF post HAS. No hubo en esta casuística complicaciones directamente atribuíbles a la FLT. El bajo riesgo de la FLT la convierte en una opción válida como parte del manejo integral de la HAS aneurismática, a la espera de estudios prospectivos que clarifiquen el rol de esta intervención.
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Humanos , Hemorragia Subaracnoidea/cirugía , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/terapia , Derivación Ventriculoperitoneal , Hidrocefalia/cirugía , Hidrocefalia/etiología , Hidrocefalia/prevención & controlRESUMEN
AIM: To determine efficacy and tolerability of dutogliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in patients with type 2 diabetes mellitus. METHODS: This was a 12-week, multicentre, randomized, double-blind, placebo-controlled trial in 423 patients with type 2 diabetes with suboptimal metabolic control. Following a 2-week single-blind placebo run-in, patients aged 18-75 years with a body mass index of 25-48 kg/m(2) and baseline HbA1c of 7.3-11.0% were randomized 2:2:1 to receive once-daily oral therapy with either dutogliptin (400 or 200 mg) or placebo on a background medication of either metformin alone, a thiazolidinedione (TZD) alone or a combination of metformin plus a TZD. RESULTS: Average HbA1c at baseline was 8.4%. Administration of dutogliptin 400 and 200 mg for 12 weeks decreased HbA1c by -0.52% (p < 0.001) and -0.35% (p = 0.006), respectively (placebo-corrected values), with absolute changes in HbA1c for the 400 mg, 200 mg and placebo groups of -0.82, -0.64 and -0.3%, respectively. The proportion of patients achieving an HbA1c < 7% was 27, 21 and 12% at dutogliptin doses of 400 and 200 mg or placebo, respectively (p = 0.008 for comparison of 400 mg vs. placebo). Fasting plasma glucose (FPG) levels were significantly reduced in both active treatment groups compared to placebo: the placebo-corrected difference was -1.00 mmol/l (p < 0.001) for the 400 mg group and -0.88 mmol/l (p = 0.003) for the 200 mg group. Dutogliptin caused significantly greater reductions in postprandial glucose AUC (0-2h) in both the 400 and 200 mg groups (placebo corrected values -2.58 mmol/l/h, p < 0.001 and -1.63 mmol/l/h, p = 0.032, respectively). In general, patients tolerated the study drug well. There were minor, not clinically meaningful differences in adverse events (AEs) between dutogliptin-treated patients and placebo controls, and 60% of all reported AEs were mild. Vital signs and body weight were stable, and routine safety laboratory parameters did not change compared with placebo. Trough ex vivo DPP4 inhibition at the end of the 12-week treatment period was 80 and 70%, at the 400 and 200 mg doses of dutogliptin, respectively. CONCLUSIONS: Dutogliptin treatment for 12 weeks improved glycaemic control in patients with type 2 diabetes who were on a background medication of metformin, a TZD or metformin plus a TZD. Tolerability was favourable for both doses tested. The 400 mg dose of dutogliptin resulted in larger changes of HbA1c and FPG and more subjects reached an HbA1c target of < 7% than the 200 mg dose.
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Ácidos Borónicos/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/administración & dosificación , Adolescente , Adulto , Anciano , Diabetes Mellitus Tipo 2/metabolismo , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To determine the efficacy and tolerability of PHX1149, a novel dipeptidyl peptidase-4 (DPP4) inhibitor, in patients with type 2 diabetes. METHODS: This is a multicentre, randomized, double-blind, placebo-controlled, 4-week study in patients with type 2 diabetes with suboptimal metabolic control. Patients with a baseline haemoglobin A(1c) (HbA(1c)) of 7.3 to 11.0% were randomized 1 : 1 : 1 : 1 to receive once-daily oral therapy with either PHX1149 (100, 200 or 400 mg) or placebo; patients were on a constant background therapy of either metformin alone or metformin plus a glitazone. RESULTS: Treatment with 100, 200 or 400 mg of PHX1149 significantly decreased postprandial glucose area under the curve AUC(0-2 h) by approximately 20% (+0.11 +/- 0.50, -2.08 +/- 0.51, -1.73 +/- 0.49 and -1.88 +/- 0.48 mmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.002, 0.008 and 0.004 vs. placebo). Postprandial AUC(0-2 h) of intact glucagon-like peptide-1, the principal mediator of the biological effects of DPP4 inhibitors, was increased by 3.90 +/- 2.83, 11.63 +/- 2.86, 16.42 +/- 2.72 and 15.75 +/- 2.71 pmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p = 0.053, 0.001 and 0.002 vs. placebo). Mean HbA(1c) was lower in all dose groups; the placebo-corrected change in the groups receiving 400 mg PHX1149 was -0.28% (p = 0.02). DPP4 inhibition on day 28 was 53, 73 and 78% at 24 h postdose in the groups receiving 100, 200 and 400 mg PHX1149, respectively. There were no differences in adverse events between PHX1149-treated and placebo subjects. CONCLUSIONS: Addition of the DPP4 inhibitor PHX1149 to a stable regimen of metformin or metformin plus a glitazone in patients with type 2 diabetes was well tolerated and improved blood glucose control.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Tiazolidinedionas/uso terapéutico , Administración Oral , Adulto , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Periodo Posprandial , Resultado del TratamientoRESUMEN
Se presenta el caso de una menor, previamente sana, que ingirió accidentalmente una dosis de 800mg. de carbamazepina. La paciente ingresa letárgica, en Glasgow 8, requiriendo intubación y manejo en Unidad de Cuidados Intensivos Pediátricos; se practicó lavado gástrico y se administró carbón activado. Durante su hospitalización presentó 4 episodios convulsivos. Los niveles de carbamazepina medidos cerca de 12 horas luego de la ingesta fueron de 19,3 ugr/ml. La eliminación del fármaco en esta paciente (siguiendo una cinética de orden 0) fue de 0,67 ugr/ml/hora. Convulsiones paradojales (por ser provocadas por un anticonvulsivante) han sido descritas infrecuentemente en la infancia como complicación de la intoxicación por carbamazepina; en esta paciente se observaron con niveles plasmáticos menores a aquellos informados habitualmente en la literatura. La paciente evolucionó favorablemente, con recuperación progresiva de conciencia y ataxia, la cual persistió por algunos días.
We report the case of a previously healthy child who accidentally ingested 800 mgs of carbamazepine. On arrival, the patient was lethargic (Glasgow 8), requiring intubation; she was admitted to the ICU and treated with gastric lavage and activated charcoal; during the course of her hospitalization she presented 4 convulsive episodes. The plasma level of carbamazepine, measured approximately 12 hours after ingestion, was 19,3 ugr/ml. The elimination rate (zero-order kinetic) was approximately 0.67 mg/L per hour. Paradoxical seizures have been described infrequently in childhood as a complication of carmazepine overdose; in this patient, they appeared with lower plasma levels than the usually reported in the literature. The patient evolved favorably, with progressive recuperation of conscience and persistent ataxia for a few days.
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Humanos , Femenino , Preescolar , Carbamazepina/envenenamiento , Intoxicación/diagnóstico , Carbón Orgánico/uso terapéutico , Intoxicación/terapia , Lavado GástricoRESUMEN
Este artículo trata las relaciones entre la psiquiatría clínica, corrientes como el psicoanálisis relacional y la literatura postmoderna, en particular las novelas de Paul Auster. Se propone el hallazgo de un cuadro psicopatológico recurrente presente a lo largo de las novelas mayores de Auster, conformado por un trastorno de stress postraumático en que predominan los síntomas disociativos, y se analiza este cuadro como metáfora de una concepción de identidad subyacente, que considera a esta última como un proceso cambiante, dinámico y contingente.
This paper considers the affinities among clinical psychiatry, relational psychoanalysis theories, and post-modern literature, particularly in the work of Paul Auster. A recurrent psychopathological entity is found throughout Paul Auster`s major novels: post traumatic stress disorder in which dissociation symptoms prevail. This is analyzed as a metaphor of an underlying conception of selfhood, which considers the latter as a shifting, dynamic, and contingent process.
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Humanos , Crisis de Identidad , Psicoanálisis , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/etiología , Literatura , PosmodernismoRESUMEN
Se reporta un caso de embarazo ectópico tubario bilateral. Se analiza el cuadro clínico y su dificultad diagnóstica.
Asunto(s)
Adulto , Humanos , Femenino , Embarazo , Embarazo Tubario/cirugía , Embarazo Tubario/diagnóstico , Embarazo Múltiple , Dolor Abdominal/etiología , Trompas UterinasRESUMEN
The University of the West Indies (UWI) comprises three campuses located on three different islands. Two of the Campuses, Mona in Jamaica and St Augustine in Trinidad & Tobago offer full medical programmes, i.e. both basic sciences and clinical training. At Cave Hill, where basic sciences courses are not offered, students are drawn from the traditional school at Mona or the Problem Based Learning (PBL) school at St Augustine to follow a common clinical programme. After 24 months of clinical training consisting of a minimum of 12 clerkships these students take identical examinations in Medicine & Therapeutics, Surgery and Obstetrics & Gynaecology. In this paper the results of the final clinical examinations at Cave Hill for the five-year period 1995-99 have been analysed, comparing the performances of students drawn from Mona with those from St Augustine. We found that, except for a few isolated cases, there were no significant differences in the performance of the two groups of students. These results suggest that the delivery of a significant component of a basic sciences programme by a well-planned PBL system is unlikely to produce substandard students at the end of their clinical training.
Asunto(s)
Educación de Pregrado en Medicina/métodos , Evaluación Educacional , Modelos Educacionales , Aprendizaje Basado en Problemas , Prácticas Clínicas , Medicina Clínica/educación , Curriculum , Educación de Pregrado en Medicina/organización & administración , Evaluación Educacional/normas , Evaluación Educacional/estadística & datos numéricos , Cirugía General/educación , Ginecología/educación , Humanos , Obstetricia/educación , Indias OccidentalesRESUMEN
This work presents data on the relative diversity, abundance, and distribution patterns of primates in a 20 km2 area of the Tapiche River in the Peruvian Amazon. Population data were collected while the study area was both inundated and dry (March to September 1997) using conventional line-transect census techniques. Survey results reflected the presence of 11 primate species, but population parameters on only eight of the species will be presented, including saddleback tamarins (Saguinus fuscicollis), Bolivian squirrel monkeys (Saimiri boliviensis), brown capuchins (Cebus apella), white-fronted capuchins (Cebus albifrons), monk sakis (Pithecia monachus), red titi monkeys (Callicebus cupreus), red uakaris (Cacajao calvus), and red howler monkeys (Alouatta seniculus). Woolly monkeys (Lagothrix lagotricha), night monkeys (Aotus nancymaae), and pygmy marmosets (Callithrix pygmaea) were also seen in the area. The data for the smaller-bodied primates is similar to that reported almost 18 years earlier, but the data for the larger-bodied primates reflect a loss in the number of animals present in the area. Pressure from hunters and the timber industry may account for declining numbers of large-bodied primates, while it appears that natural features peculiar to the conservation area contribute to the patchy pattern of distribution.
Asunto(s)
Ecosistema , Primates/crecimiento & desarrollo , Animales , Conservación de los Recursos Naturales , Perú , Densidad de Población , Estaciones del AñoRESUMEN
Resolution of infection by Leishmania sp. is critically dependent on activation of CD4(+) T helper cells. Naive CD4(+) T helper cells are primed by dendritic cells which have responded to an activation signal in the periphery. However, the role of Leishmania-infected dendritic cells in the activation of an anti-Leishmania immune response has not been comprehensively addressed. Using the highly controlled model system of bone marrow-derived dendritic cell infection by Leishmania mexicana cultured in vitro, we show that uptake of L. mexicana parasites does not result in activation of immature dendritic cells or secretion of IL-12. Incubation with L. mexicana promastigotes results in the activation of a small percentage of dendritic cells which do not appear to contain whole parasites. Activation of dendritic cells is not suppressed by infection, since infected cells can be fully activated on addition of activating stimuli. Therefore, uptake of intact Leishmania mexicana parasites is not sufficient to activate dendritic cells in vitro. We propose that these data provide a basis for interpreting the interactions between dendritic cells and all Leishmania sp.
Asunto(s)
Células Dendríticas/parasitología , Leishmania mexicana/inmunología , Animales , Antígenos CD/análisis , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/parasitología , Células Cultivadas , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Inmunofenotipificación , Interleucina-12/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBARESUMEN
We analysed 67 samples from Brazilian children of diverse ethnic origins with acute lymphoblastic leukaemia (ALL) for the presence of the TEL-AML1 fusion gene transcripts using reverse transcription polymerase chain reaction (RT-PCR). All 12 positive cases (20% of the 60 B-cell precursor ALL) had common (CD10+) ALL with a mean age of 4 years (range 1-10 years). We conclude that the frequency, age, distribution and clinical features of the TEL-AML1 fusion gene-positive ALL is similar in the diverse ethnic backgrounds of the Brazilian children to that in other countries with predominantly white Caucasian or oriental ethnicity. Apparent exceptions to this generality are discussed.
Asunto(s)
Linfoma de Burkitt/genética , Frecuencia de los Genes , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Población Negra , Brasil , Linfoma de Burkitt/etnología , Niño , Preescolar , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Femenino , Humanos , Lactante , Leucemia-Linfoma de Células T del Adulto/etnología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Población BlancaRESUMEN
Habitual xylitol gum-chewing may have a long-term preventive effect by reducing the caries risk for several years after the habitual chewing has ended. The goal of this report was (1) to determine if sorbitol and sorbitol/xylitol mixtures provide a long-term benefit, and (2) to determine which teeth benefit most from two-year habitual gum-chewing - those erupting before, during, or after habitual gum-chewing. Children, on average 6 years old, chewed gums sweetened with xylitol, sorbitol, or xylitol/sorbitol mixtures. There was a "no-gum" control group. Five years after the two-year program of habitual gum-chewing ended, 288 children were re-examined. Compared with the no-gum group, sorbitol gums had no significant long-term effect (relative risk [RR], 0.65; 95% confidence interval [c.i.], 0.39 to 1.07; p < 0.18). Xylitol gum and, to a lesser extent, xylitol/sorbitol gum had a long-term preventive effect. During the 5 years after habitual gum-chewing ended, xylitol gums reduced the caries risk 59% (RR, 0.41; 95% c.i., 0.23 to 0.75; p < 0.0034). Xylitol-sorbitol gums reduced the caries risk 44% (RR, 0.56; 95% c.i., 0.36 to 0.89; p < 0.02). The long-term caries risk reduction associated with xylitol strongly depended on when teeth erupted (p < 0.02). Teeth that erupted after 1 year of gum-chewing or after the two-year habitual gum use ended had long-term caries risk reductions of 93% (p < 0.0054) and 88% (p < 0.0004), respectively. Teeth that erupted before the gum-chewing started had no significant long-term prevention (p < 0.30). We concluded that for long-term caries-preventive effects to be maximized, habitual xylitol gum-chewing should be started at least one year before permanent teeth erupt.
Asunto(s)
Goma de Mascar , Caries Dental/prevención & control , Belice/epidemiología , Goma de Mascar/estadística & datos numéricos , Distribución de Chi-Cuadrado , Niño , Estudios de Cohortes , Índice CPO , Caries Dental/epidemiología , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Riesgo , Sorbitol/uso terapéutico , Factores de Tiempo , Erupción Dental , Xilitol/uso terapéuticoRESUMEN
Habitual xylitol gum-chewing may have a long-term preventive effect by reducing the caries risk for several years after the habitual chewing has ended. The goal of this report was (1) to determine if sorbitol and sorbitol/xylitol mixture provide a long-term benefit, and (2) to determine which teeth benefit most from two-year habitual gum-chewing - those erupting before, during, or after habitual gum-chewing. Children, on average 6 years old, chewing gums sweetened with xylitol, sorbitol, or xylitol/sorbitol mixture. There was a "no gum" control group. Five years after the two-year program of habitual gum-chewing ended, 288 children were re-examined. Compared with the no-gum group, sorbitol gums had no significant long-term effect (relative risk (RR), 0.65; 95 percent confidence interval [c.i]. 0.39 to 1.07; p < 0.18). Xylitol gums and, to a lesser extent, xylitol/sorbitol gum had a long-term preventive effect. During the 5 years after habitual gum-chewing ended, xylitol gums reduced the caries risk 59 percent (RR, 0.41; 95 percent c.i., 0.23 to 0.75; p < 0.0034). Xylitol-sorbitol gums reduced the caries risk 44 percent (RR, 0.56; 95 percent c.i., 0.36 to 0.89; p < 0.02). The long-term caries risk reduction associated with xylitol strongly depended on when teeth erupted (p < 0.02). Teeth that erupted after 1 year of gum-chewing or after the two-year habitual gum use ended had long-term caries risk reduction of 93 percent (p < 0.0054) and 88 percent (p < 0.0004), respectively. Teeth that erupted before the gum-chewing started had no significant long-term prevention (p < 0.30). We concluded that for long-term caries-preventive effects to be maximized, habitual xylitol gum-chewing should be started at least one year before permanent teeth erupt.(AU)
Asunto(s)
Niño , Femenino , Humanos , Masculino , Goma de Mascar , Caries Dental/prevención & control , Belice/epidemiología , Goma de Mascar/estadística & datos numéricos , Distribución de Chi-Cuadrado , Estudios de Cohortes , Caries Dental/epidemiología , Índice CPO , Incidencia , Estudios Longitudinales , Riesgo , Sorbitol/uso terapéutico , Factores de Tiempo , Erupción Dental , Xilitol/uso terapéuticoRESUMEN
A previous caries trial (Belize studies) involved the usage of sucrose chewing-gum for a period of 40 months in one group of initially 10-year-old subjects in an environment of high sugar consumption, high caries activity, and limited access to restorative care. After the termination of the 40-month supervised sucrose gum usage, the 109 subjects of the original sucrose group retrieved at the endpoint of the original trial were invited to participate in a xylitol chewing-gum programme (involving the usage of the '100% pellet-shaped formular') for 16 months. The average daily consumption level of xylitol was up to 14 g per subject, normally used in seven daily chewing episodes. Although most subjects used chewing-gum at schools and received their gum portions from a school official, gum chewing during these 16 months was mostly unsupervised. After 16 months, 83 subjects (76%; mean age 14.9 years) were retrieved. The caries status of these subjects was examined by the same calibrated, blinded examiners as in the original trial. To mask the examiners, 141 similar non-participating subjects were recruited from the same school classes and were examined in a random order with the gum-using subjects, according to the same standard routine. The intensified xylitol gum usage for 16 months was associated with a reduction of the mean DMFS score from 10.9 (at 40 months) to 9.3 (at 56 months, p = 0.0013) and a reduction in caries rate from 20.1 caries onsets per 1,000 surface-years (40-month period average rate) to 10.2 caries onsets per 1,000 surface-years. The reduction in DMFS score resulted mostly from the change in the D component of the index and possibly reflected a stabilisation of the caries process and rehardening of some caries lesions to a non-progressive carious state.
Asunto(s)
Goma de Mascar , Caries Dental/terapia , Remineralización Dental/métodos , Xilitol/administración & dosificación , Adolescente , Belice/epidemiología , Índice CPO , Caries Dental/epidemiología , Caries Dental/etiología , Humanos , Incidencia , Método Simple Ciego , Sacarosa/efectos adversosRESUMEN
A hybrid problem based learning (PBL) and traditional medical programme was started at the Trinidad campus of the University of the West Indies in 1989. Analyses were carried out to determine the extent to which the entrance qualifications of the students were related to their performances at the examinations in the Phase I (preclinical and paraclinical) and Phase II (clinical) programmes. Students who were admitted on the basis of their results in the secondary school General Certificate of Examination (GCE), 'A' level scored higher at the Phase I, but not at the Phase II, level than those who already had university education. Among the 'A' level students, there was positive correlation between the total 'A' level scores and the examination marks in the medical programme, particularly at the Phase I level. Furthermore, multiple regression analyses indicated that the grades in 'A' level Chemistry and, to a lesser extent in Biology, had the most influence on performances at the Phase I examinations, with much less influence on performances at the Phase II examinations. These results suggest that good grades at 'A' level examinations are significant factors, but not the only important ones, that favour high achievement in the initial stages of this type of PBL/traditional medical programme.
Asunto(s)
Aprendizaje Basado en Problemas , Evaluación Educacional , Educación de Pregrado en Medicina , Trinidad y TobagoRESUMEN
A hybrid problem based learning (PBL) and traditional medical programme was started at the Trinidad campus of the University of the West Indies in 1989. Analyses were carried out to determine the extent to which the entrance qualifications of the students were related to their performances at the examinations in the Phase I (preclinical and paraclinical) and Phase II (clinical) programmes. Students who were admitted on the basis of their results in the secondary school General Certificate of Examination (GCE), 'A' level scored higher at the Phase I, but not at the Phase II, level than those who already had university education. Among the 'A' level students, there was positive correlation between the total 'A' level scores and the examination marks in the medical programme, particularly at the Phase I level. Furthermore, multiple regression analyses indicated that the grades in 'A' level Chemistry and, to a lesser extent in Biology, had the most influence on performances at the Phase I examinations, with much less influence on performances at the Phase II examinations. These results suggest that good grades at 'A' level examinations are significant factors, but not the only important ones, that favour high achievement in the initial stages of this type of PBL/traditional medical programme.