Classic and Atypical Late Infantile Neuronal Ceroid Lipofuscinosis in Latin America: Clinical and Genetic Aspects, and Treatment Outcome with Cerliponase Alfa.

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants, with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa. Materials and methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed. Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype (n = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype (n = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values. Discussion and conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes.

3-D Ultrasonographic Quantification of Hand and Calf Muscle Volume: Statistical Shape Modeling Approach.

Accurate acquisition and segmentation of muscles are essential in 3-D freehand ultrasonography (US) to estimate in vivo muscle volume, but the source of segmentation inaccuracy in shape variation has never been the focus. This study was aimed at investigating reliability of 3-D US in the acquisition and segmentation for muscle volume of two muscles of different sizes and in identifying a primary source of measurement difference. The lateral gastrocnemius and flexor pollicis brevis of 12 healthy adults were assessed using freehand 3-D US scans. The motion-tracking data of the probe were synchronized with the B-mode ultrasound scan to reconstruct 3-D muscle volume. Statistical shape modeling was used to provide a spatial segmentation volume difference that further explains the variation around segmentation repeatability. The absolute difference of the flexor pollicis brevis was 3.5 percentage points greater than that for the lateral gastrocnemius. The highest measurement differences were observed when for inter-acquirer analysis. Statistical shape modeling revealed that the primary segmentation volume differences were at the muscle ends and edges, where the muscle interfaces with the surrounding muscles. Three-dimensional US is a reliable tool in the clinical setting, but care must be taken to ensure that acquisition and segmentation are consistent, particularly in a small muscle that interfaces with tendons and other soft tissues.

Transport and release of colloidal 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots in human umbilical vein endothelial cells.

Colloidal semiconductor quantum dots (QDs) have been extensively researched and developed for biomedical applications, including drug delivery and biosensing assays. Hence, it is pivotal to understand their behavior in terms of intracellular transport and toxicological effects. In this study, we focused on 3-mercaptopropionic acid-coated CdSe-CdS/ZnS core-multishell quantum dots (3MPA-QDs) converted from the as-grown octadecylamine-coated quantum dots (ODA-QDs) and their direct and dynamic interactions with human umbilical vein endothelial cells (HUVECs). Live cell imaging using confocal fluorescence microscopy showed that 3MPA-QDs first attached to and subsequently aggregated on HUVEC plasma membrane ~25 min after QD deposition. The aggregated QDs started being internalized at ~2 h and reached their highest internalization degree at ~24 h. They were released from HUVECs after ~48 h. During the 48 h period, the HUVECs responded normally to external stimulations, grew, proliferated and wound healed without any perceptible apoptosis. Furthermore, 1) 3MPA-QDs were internalized in newly formed LysoTracker-stained early endosomes; 2) adenosine 5'-triphosphate-induced [Ca2+]i modulation caused a transient decrease in the fluorescence of 3MPA-QDs that were attached to the plasma membrane but a transient increase in the internalized 3MPA-QDs; and 3) fluorescence signal modulations of co-stained LysoTracker and QDs induced by the lysosomotropic agent Gly-Phe-ß-naphthylamide were spatially co-localized and temporally synchronized. Our findings suggest that 3MPA-QDs converted from ODA-QDs are a potential nontoxic fluorescent probe for future use in clinical applications. Moreover, the photophysical strategy and techniques reported in this work are easily applicable to study of direct interactions between other nanoparticles and live cells; contributing to awareness and implementation of the safe applications of nanoparticles.

Caracterización clínica y estado actual de los pacientes con Síndrome de Asperger de 0 a 16 años, atendidos en la Fundación Liga Central Contra la Epilepsia y el Hospital de la Misericordia de Bogotá, Colombia / Clinical characterization and current status of the patients with Asperger's Syndrome from 0 to 16 years, served by the Foundation Central League Against Hospital of Mercy, Bogotá, Colombia

El objetivo del presente estudio fue determinar los hallazgos clínicos, paraclínicos, epidemiológicos, y de pruebas de tamizaje y de diagnóstico en el síndrome de Asperger, en los casos que se detectaron en la Fundación Liga Central Contra La Epilepsia y la Fundación Hospital de la Misericordia entre los años 2004 y 2007. Hasta la fecha existen pocos artículos de series clínicas sobre este síndrome en la literatura médica, se ha informado que es un trastorno sub-diagnosticado en Colombia. Este estudio describe el síndrome con detalle, mostrando sus características en nuestra población, con el fin de ofrecer una mejor información para diagnóstico, tratamiento, seguimiento y prevención.

The objective of this study was to determine the clinical, paraclinical, epidemiological, and screening tests and diagnostic findings in Asperger syndrome, in the cases that were detected in the Central Foundation League Against Epilepsy and the Foundation of the Hospital of Misericordi between the years 2004 and 2007. To date, there are few articles of clinical series on this syndrome in the medical literature, it has been reported that it is a sub -diagnosed disorder in Colombia. This study describes the syndrome with detail, showing all their characteristics in our population, in order to provide better information for diagnosis, treatment, follow-up and prevention.

Avances y perspectivas en Síndrome de Asperger / Progress and prospects in Asperger Syndrome

El síndrome de Asperger es un trastorno generalizado del desarrollo, fue descrito por Hans Asperger en 1944. Se caracteriza por una marcada alteración social, dificultades en la comunicación, déficit en la capacidad de juego y un rango de comportamiento e intereses repetitivos, sin un retardo significativo en el lenguaje, ni cognitivo. Considerando la importancia del tema actualmente, en este se hace una revisión amplia sobre el tema que abraca aspectos como: características clínicas, alteraciones al examen físico, posibles alteraciones estructurales y funcionales. También se especifican los criterios del DSM-IV, del diagnóstico diferencial y del diagnóstico diferencial. Finalmente, se puntualizan algunos aspectos relacionados con la genética y el tratamiento.

Asperger syndrome is a pervasive developmental disorder; it was described by Hans Asperger in 1944. It is characterized by a marked social disruption, difficulties in communication, deficit in the ability to play and a range of interests and repetitive behavior, without a significant language or cognitive delay. Considering the current importance of the item, this is done in a comprehensive review on the subject that covers aspects such as: clinical features, alterations to the physical examination, and possible structural and functional alterations. Also the DSM-IV criteria and the differential diagnosis are specified. Finally, some of the aspects related to the genetics and treatment are discussed.

Programa de rehabilitación integral en pacientes con dolor cronico de espalda: un estudio de caso / Rehabilitation program in patients with chronic back pain: a case study

La utilización de estrategias combinadas para el manejo de pacientes con dolor crónico, ha demos-trado eficacia en su recuperación. Este trabajo tiene como objetivo mostrar la aplicación de abor-dajes psicológicos y fisioterapéuticos en la rehabilitación de un paciente masculino de 62 años con dolor crónico de espalda. Las estrategias fisioterapéuticas aplicadas se basaron en la aplicación de técnicas Tens, Ultrasonido, ejercicios de balonterapia, ejercicios isométricos e isotónicos, medios físicos, técnica de Mckenzy y ejercicios de cadenas cinética, las cuales se suministraron con una duración de 1 hora por cada sesión diaria, durante un periodo de 15 días y el efecto del tratamien-to aplicado se evaluó mediante la valoración de problemas osteomusculares (OM). El tratamiento psicológico de acompañamiento se basó en un entrenamiento cognitivo conductual (ECC) sumi-nistrado con una periodicidad semanal; el nivel de mejora de vida del paciente fue medido con la escala de ansiedad Hamilton, y el cuestionario de estrategias de afrontamiento (CIQ) y Euro-gol. Las valoraciones fisioterapéuticas se aplicaron antes, durante y después del tratamiento, mientras que las valoraciones psicológicas se aplicaron antes y después, y demostraron una rehabilitación integral eficiente; disminuyendo el dolor crónico de espalda, aumentando la movilidad y mejoran-do la calidad de vida al disminuir los índices de dolor a la palpación y al movimiento, medida en escala numérica de Borg. Igualmente se observó disminución en el índice de discapacidad lumbar de Oswestry, disminución en los niveles de ansiedad y recuperación total del paciente lo que de-muestra que la rehabilitación integral del paciente fue eficaz.

The use of combined strategies for the management of patients with chronic pain has shown effectiveness in recovery, so this work shows the application of psychological approaches and physiotherapy in the rehabilitation of a 62 year old male patient with chronic back pain. The applied physiotherapy strategies were based on the application of techniques such as Tens, Ul-trasound, balloon-therapy exercises, isometric and isotonic exercises, physical mediums, the McKenzy technique and kinetic chain exercises, which were provided as one hour long daily session, for a period of 15 days and the effect of the applied treatment was evaluated by assessing musculoskeletal problems (OM). The accompanying psychological treatment was based on a cognitive behavioral training (ECC) that was performed weekly; the level of life improvement of the patients was measured with the Hamilton anxiety scale, the coping strategies questionnaire (CIQ) and Euro-gol. The physiotherapy assessments were applied before, during and after the treatment, while psychological assessments were applied before and after and showed an efficient complete rehabilitation, reducing chronic back pain, increasing mobility and improving quality of life by reducing the indexes of tenderness to pain and movement, with the Borg numerical scale. Furthermore, it was observed that the lumbar disability index of Oswestry also decreased, as well as the anxiety levels and there was a total patient recovery demonstrating that comprehen-sive patient rehabilitation was effective.

Anestesia endovenosa en curetaje uterino -Comparación etomidato, clonazapan-tiopental-ketamina, tiopental-midazolan, ketamina-fentanyl y tiopental

Se analizan 118 pacientes sometidas a curetaje uterino, sanas por lo demás, en cuento a su comportamiento hemodinámico y de calidad anestésica en 5 técnicas anestésicas endovenosas diferentes, distribuidas en cinco grupos: Clonazepan-fentanyl-etomidato, tiopental, midazolam-ketamina, tiopental-ketamina y fentanyl-tiopental. La asociación fentanyl-tiopental mostró ser la más estable hemodinámicamente y tener la menor cantidad de efectos secundarios; el etomidato es comparativamente tan hemodinámicamente estable como fentanyl-tiopental, pero la presencia de mioclonias y el riesgo de convulsiones son limitantes impòrtantes. La ketamina produce cambios hemodinámicos y efectos psicotomiméticos que no fueron controlados adecuadamente por el fármaco asociado, y son incluso potenciados por el tiopental. El tiopental produce grandes variaciones hemodinámicas como reflejo de su efecto cardiodepresor. Se recomienda hacer un nuevo estudio comparativo con otros fármacos y a mayores dosis de las usadas por nosotros

Evolución del concepto de lepra e instituciones en Colombia / Evolution of the concept of leprae and institutions in Colombia

Este trabajo refleja la evolución del concepto de lepra que dependió de circunstancias históricas determinadas y estrechamente relacionadas con el manejo institucional. Notamos que a pesar de los avances científicos no se ha logrado determinar muchos aspectos de la enfermedad tan importantes como los postulados de Koch. Desde los leprocomios iniciales, con los cuales se intentó solucionar el problema de salud pública que reemplazaba la lepra hasta el manejo individualizado, integral y ambulatorio actúal, se evidencia una inadecuada e irregular enfoque del problema que da como resultado en que su control no haya sido el esperado y que aún en el momento no se cuente con una estadística veráz acerca de la mágnitud del mismo en el País