Diabetes mellitus por mutación en el gen de glucokinasa: caso clínico / Diabetes mellitus caused by a mutation of glucokinase gene: report of an affected family

Maturity-Onset Diabetes of the Young (MODY) refers to a heterogeneous group of monogenic diabetes. Unlike other types of MODY characterized by genetic defects in transcription factors, MODY 2 is triggered by metabolic alterations caused by mutations of glucokinase (GCK), the first enzyme of the glycolytic pathway. We report a three-generation Chilean family with multiple cases affected with this disease. The index case is a patient who presented severe neonatal hyperglycemia (831 mg/dl, without ketosis) requiring continuous infusion of insulin, which was suspended after 48 hours with normalization of blood glucose. Subsequently, continuous glucose monitoring at 4 months of age revealed 47% of tissue glucose levels above 140 mg/dl, with fasting glucose levels between 120 and 166 mg/dl. The genetic analysis revealed a previously reported mutation in heterozygous state of the GCK gene (c.148C>T; p.His50Tyr). This mutation was also identified in more than one affected relative in the last two generations, with a transmission pattern suggestive of dominant inheritance. GCK gene sequencing led to a correct molecular diagnosis of MODY 2 while bioinformatic analysis indicated the possible molecular causes of the enzyme dysfunction. The knowledge of the molecular diagnosis allowed an adequate medical treatment for this disease.

[Diabetes mellitus caused by a mutation of glucokinase gene. Report of an affected family]. / Diabetes mellitus por mutación en el gen de glucokinasa. Caso clínico.

Maturity-Onset Diabetes of the Young (MODY) refers to a heterogeneous group of monogenic diabetes. Unlike other types of MODY characterized by genetic defects in transcription factors, MODY 2 is triggered by metabolic alterations caused by mutations of glucokinase (GCK), the first enzyme of the glycolytic pathway. We report a three-generation Chilean family with multiple cases affected with this disease. The index case is a patient who presented severe neonatal hyperglycemia (831 mg/dl, without ketosis) requiring continuous infusion of insulin, which was suspended after 48 hours with normalization of blood glucose. Subsequently, continuous glucose monitoring at 4 months of age revealed 47% of tissue glucose levels above 140 mg/dl, with fasting glucose levels between 120 and 166 mg/dl. The genetic analysis revealed a previously reported mutation in heterozygous state of the GCK gene (c.148C>T; p.His50Tyr). This mutation was also identified in more than one affected relative in the last two generations, with a transmission pattern suggestive of dominant inheritance. GCK gene sequencing led to a correct molecular diagnosis of MODY 2 while bioinformatic analysis indicated the possible molecular causes of the enzyme dysfunction. The knowledge of the molecular diagnosis allowed an adequate medical treatment for this disease.

Factores predictivos de éxito tras una sesión única de litotricia extracorpórea de cálculos urinarios a las tres semanas de seguimiento / Single-Session Extracorporeal Shock Wave Lithotripsy for Urinary Calculi: Factors Predicting Success after Three Weeks of Follow-Up

Objetivo: Identificar factores predictivos de éxito después de una sesión única de litotricia extracorpórea por ondas de choque (LEOC) a las tres semanas de seguimiento. Material y métodos: Se revisaron los registros clínicos de 116 pacientes con cálculos urinarios únicos sometidos a LEOC entre octubre 2007 y agosto 2009. Las tomografías axiales computarizadas preoperatorias de todos los pacientes fueron revisadas por dos radiólogos en desconocimiento del desenlace clínico. El éxito fue definido como la desaparición completa del cálculo o la persistencia de fragmentos ≤ 2mm en la radiografía simple realizada durante las tres primeras semanas de seguimiento. El impacto de factores clínicos y radiológicos fue evaluado utilizando regresión logística. Resultados: La tasa de éxito de LEOC a las tres semanas de seguimiento fue del 49,1%. Tamaño < 8mm, área del cálculo < 30mm2, localización en el uréter distal, densidad < 1.000 UH y fragmentación intraoperatoria demostraron una significativa asociación con éxito en el análisis univariado (p<0,05). Área del cálculo<30mm2 (OR: 2,9), localización en uréter distal (OR: 3,4) y fragmentación intraoperatoria (OR: 4,2) fueron factores predictivos de éxito en el análisis multivariado (p<0,05). Conclusiones: El área del cálculo y la localización en el uréter distal son útiles en el momento de decidir acerca de la realización de una LEOC. Sin embargo, la resolución exitosa de solamente la mitad de los casos bajo los criterios evaluados recalca la relevancia de informar al paciente de la eventual necesidad de tratamientos adicionales después de una sesión única de LEOC (AU)

Introduction: The aim of this study was to identify predictive factors of success following a single-session of shock wave lithotripsy (SWL) at 3 weeks of follow-up in our center. Material and methods: The medical records of 116 patients with solitary urinary calculi who underwent single-session SWL in our department between October 2007 and August 2009 were reviewed. All preoperative unenhanced computed axial tomographies were reviewed by two radiologists blinded to clinical outcome. Success was defined as complete clearance or the persistence of fragments ≤ 2mm on a plain film at 3 weeks of follow-up. The impact of clinical and radiological factors on success was assessed by univariate and multivariate analyses. Results: The single-session SWL success rate at 3 weeks was 49.1%. Stone size <8mm, stone area < 30mm2, stone location (mid- and distal ureter), stone density <1000 HU and intraoperative fragmentation showed a significant association with SWL success in the univariate analysis (p<0.05). Stone area (OR 2.9), ureteral stone location (OR 3.4) and intraoperative fragmentation (OR 4.2) were the only predictors of success in the multivariate analysis. Conclusions: Stone area and ureteral stone location provide important information when deciding about the indication of a SWL in a patient with stone disease. However, successful resolution of only half of the cases after a single session at 3 weeks in our series undermines the relevance of informing patients about the potential need for additional treatment (AU)

[Single-session extracorporeal shock wave lithotripsy for urinary calculi: factors predicting success after three weeks of follow-up]. / Factores predictivos de éxito tras una sesión única de litotricia extracorpórea de cálculos urinarios a las tres semanas de seguimiento.

INTRODUCTION: The aim of this study was to identify predictive factors of success following a single-session of shock wave lithotripsy (SWL) at 3 weeks of follow-up in our center. MATERIAL AND METHODS: The medical records of 116 patients with solitary urinary calculi who underwent single-session SWL in our department between October 2007 and August 2009 were reviewed. All preoperative unenhanced computed axial tomographies were reviewed by two radiologists blinded to clinical outcome. Success was defined as complete clearance or the persistence of fragments ≤ 2 mm on a plain film at 3 weeks of follow-up. The impact of clinical and radiological factors on success was assessed by univariate and multivariate analyses. RESULTS: The single-session SWL success rate at 3 weeks was 49.1%. Stone size <8 mm, stone area < 30 mm(2), stone location (mid- and distal ureter), stone density <1000 HU and intraoperative fragmentation showed a significant association with SWL success in the univariate analysis (p<0.05). Stone area (OR 2.9), ureteral stone location (OR 3.4) and intraoperative fragmentation (OR 4.2) were the only predictors of success in the multivariate analysis. CONCLUSIONS: Stone area and ureteral stone location provide important information when deciding about the indication of a SWL in a patient with stone disease. However, successful resolution of only half of the cases after a single session at 3 weeks in our series undermines the relevance of informing patients about the potential need for additional treatment.

Electrochemical behavior of atomoxetine and its voltammetric determination in capsules.

In this work, the electrochemical behavior and the analytical application of atomoxetine, a selective noradrenaline reuptake inhibitor, are studied. Atomoxetine, studied by differential pulse voltammetry and cyclic voltammetry on a glassy carbon electrode, exhibited an anodic response in aqueous media with pH between 1.5 and 7. In non-aqueous medium (acetonitrile), the drug exhibited two irreversible oxidation peaks that are diffusion controlled. From chronocoulometric studies in acetonitrile, it was determined that each oxidation signal involves two and four electrons, respectively. For analytical purposes, a differential pulse voltammetry technique in 0.1 mol L(-1) perchloric acid was selected, which exhibited adequate figures of merit. The percent recovery was 96.6+/-1.2 and the detection and quantitation limits were 6.9 x 10(-5) and 1.0 x 10(-4) mol L(-1), respectively. Also, results indicate that excipients do not interfere with the oxidation signal of atomoxetine, which leads to the conclusion that the developed method is satisfactorily selective for atomoxetine quantification in pharmaceuticals with no prior separation or extraction necessary. Finally, the proposed voltammetric method was successfully applied to both the assay and the uniformity content of atomoxetine in capsules. For comparison, high-performance liquid chromatography analysis was also performed.

Simultaneous voltammetric determination of levodopa, carbidopa and benserazide in pharmaceuticals using multivariate calibration.

An analytical methodology based on differential pulse voltammetry (DPV) on a glassy carbon electrode and the partial least-squares (PLS-1) algorithm for the simultaneous determination of levodopa, carbidopa and benserazide in pharmaceutical formulations was developed and validated. Some sources of bi-linearity deviation for electrochemical data are discussed and analyzed. The multivariate model was developed as a ternary calibration model and it was built and validated with an independent set of drug mixtures in presence of excipients, according with manufacturer specifications. The proposed method was applied to both the assay and the uniformity content of two commercial formulations containing mixtures of levodopa-carbidopa (10:1) and levodopa-benserazide (4:1). The results were satisfactory and statistically comparable to those obtained by applying the reference Pharmacopoeia method based on high performance liquid chromatography. In conclusion, the methodology proposed based on DPV data processed with the PLS-1 algorithm was able to quantify simultaneously levodopa, carbidopa and benserazide in its pharmaceuticals formulations using a ternary calibration model for these drugs in presence of excipients. Furthermore, the model appears to be successful even in the presence of slight potential shifts in the processed data, which have been taken into account by the flexible chemometric PLS-1 approach.

Electrochemical study and analytical applications for new biologically active 2-nitrophenylbenzimidazole derivatives.

The present study addresses the electrochemical behavior and the analytical applications of six 2-nitrophenylbenzimidazole derivatives with activity against Trypanosoma cruzi. When studied in a wide range of pH, by differential pulse polarography, tast polarography and cyclic voltammetry, these compounds exhibited two irreversible cathodic responses. With analytical purposes, the differential pulse polarography mode was selected, which exhibited adequate analytical parameters of repeatability, reproducibility and selectivity. The percentage of recovery was in all cases over 99%, and the detection and quantitation limits were at the level of 1 x 10(-7)mol L(-1) and 1 x 10(-6)mol L(-1), respectively. In addition, the differential pulse polarography method was successfully applied to study the hydrolytic degradation kinetic of one of the tested compounds. Activation energy, kinetic rate constants at different temperatures and half-life values of such application are reported.

Prostatectomía radical en pacientes sometidos a cirugía prostática previa / Radical prostactectomy in patients with previous prostatic surgery

El objetivo del presente trabajo fue evaluar si existen diferencias significativas entre los pacientes sometidos a PR teniendo un procedimiento quirúrgico previo sobre esta glándula. Pacientes y métodos: Se realizó un estudio retrospectivo de los pacientes sometidos a PR en quienes existió una cirugía prostática previa por patología benigna. Los datos fueron obtenidos de la revisión de la base de datos de nuestro departamento, considerando el período de mayo de 1999 hasta mayo de 2004. Resultados: En el período analizado se realizaron 54 PR, en pacientes con cirugía prostática previa (7,4 por ciento del total de pacientes sometidos a PR), con un promedio de edad de 68 años. Ocho pacientes fueron sometidos a cirugía abierta (3 operación de Millin, 5 transvesicales), el resto de los pacientes se realizó resección transuretral. El tiempo promedio entre la cirugía previa y la PR fue de 5,3 años. El 18,8 por ciento tuvo score de Gleason >=8, el 77 por ciento score de 7 y el 4,1 por ciento score <=6. El APE promedio fue de 13,2 ng/dl. El volumen tumoral alcanzó los 6,48 cc en la pieza patológica. La subetapificación clínico patológica llegó al 73,9 por ciento. Las lesiones órgano confinadas fueron 69,96 por ciento de la muestra. No hubo mortalidad operatoria. El 26,6 por ciento de los pacientes requirió transfusión de glóbulos rojos. En 73,4 por ciento de nuestra serie la cirugía no superó las tres horas. De la morbilidad derivada del procedimiento destacan 3 filtraciones de la anastomosis y 3 pacientes que presentaron estenosis de la anastomosis. La continencia alcanza al 90,3 por ciento. Discusión: En comparación con resultados publicados previamente por nuestro servicio y por otros centros en relación a PR, esta serie se diferencia en cuanto a, una cifra menor de APE promedio, mayor porcentaje de casos con score de Gleason 7 y de pacientes con lesiones órgano confinadas. El tiempo operatorio promedio es similar a otros reportes. No existen diferencias en cuanto a transfusión ni complicaciones.

Nefrectomía laparoscópica mano asistida en donante para trasplante / Hand assisted laparoscopical nephrectomy in donator for transplant

Desde el año 2001 se emplea en nuestro Hospital la nefrectomía laparoscópica mano asistida (NLMA) para donante renal. Nuestro objetivo es revisar los resultados del procedimiento y compararlos con una serie histórica de nefrectomía abierta, evaluando función renal del donante y el receptor. En el período enero 2001 agosto 2004 se realizan 34 NLMA, 24 mujeres y 10 hombres, edad promedio 39,4. Tiempo operatorio promedio 96,8 min. (60-210). Isquemia caliente promedio 5,6 min (3-15). La estadía hospitalaria promedio fue 3,4 días (2-10). La caída del hematocrito fue 5,8 por ciento promedio. Los resultados se comparan con una serie histórica de nefrectomía para donante vía abierta desde 1995 hasta enero de 2001 la cual consta de 30 pacientes. Se evalúa función renal en el receptor de nefrectomía vía abierta y NLMA mediante creatininemia, sin haber diferencias significativas a los 7 días, al mes y a los 6 meses. Es un procedimiento que permite acortar los tiempos operatorios. Por otro lado, no influye en el resultado funcional del injerto, permitiendo una rápida recuperación para el donante.

Sobrevida a largo plazo del cáncer vesical infiltrante tratado con cistectomía radical / Long time survival of advanced bladder cancer treated with radical cistectomy

El cáncer vesical es un tumor frecuente en la patología urológica y que en su forma infiltrante es muy agresivo y de mal pronóstico. La cistectomía radical es aún la principal arma terapéutica para el tratamiento de estos tumores. Este trabajo evalúa los resultados a largo plazo del cáncer invasor tratado con cistectomía radical.

Deficit in the water-maze after lesions in the anteromedial extrastriate cortex in rats.

The Morris water-maze task was used to evaluate the role of the anteromedial extrastriate visual cortex in the processing of visuospatial information in rats. Six gray male rats received bilateral ibotenic acid injections targeted stereotactically to the rostral part of the anteromedial extrastriate visual cortex. These operated subjects and six other unoperated control rats were tested in the maze. Histological analysis confirmed the localization, symmetry, and depth of lesions in the rostral part of anteromedial area (AMa) in the operated subjects. In these animals, a significantly greater latency to reach the submerged platform was found (U = 0, p = 0.004). The Morris water-maze may be considered as a reference memory task. It presents a stronger demand on the use of allocentric spatial visual cues than on the use of egocentric cues for navigation. Therefore, the present data lend support to the participation of area AMa in the integration of allocentric visuospatial cues or as a link in the memory system involved in the acquisition of this task.

Heterogeneity of carrageenans from Chondrus crispus.

Carrageenans extracted from gametophytic and sporophytic Chondrus crispus were analysed by hydrolysis, KCl fractionation and 1H NMR spectroscopy. The carrageenan from gametophytic plants is composed predominantly of two KCl insoluble fractions which contain kappa-carrageenan as the major component with 1-carrageenan and sulphated galactans as minor components. The precursor mu- and v-carrageenans were not found in the soluble fraction. The extract from sporophytic plants is composed mainly of a KCl soluble fraction which could be separated into 10 fractions by ion-exchange chromatography. The major component did not show a lambda-type structure but one of a xi-carrageenan.

Trisomía 22 / Trisomy 22

En los últimos años se han delineado tres entidades que involucran trisomía del cromosoma 22 y que comparten ciertas manifestaciones clínicas: el síndrome de ojo de gato, la trisomía parcial y la trisomía total 22, cuya existencia en recién nacidos aún está en controversia. Se describe un caso de trisomía 22 total, por translocación (15;22) "de novo", que falleció en el período de recién nacido con malformaciones pulmonares no descritas, y dos pacientes con una trisomía 22 parcial, (47, XX y XY, + der(22), t(11;22) (q25;q13) mat) debida a una segregación 3:1 en sus madres, quienes son portadoras de una translocación balanceada (11;22). Se discuten los hallazgos clínicos y citogenéticos de los probandos y sus familiares, así como los riesgos de recurrencia de estas trisomías