Altered functional connectivity and network excitability in a model of cortical dysplasia.

Focal cortical dysplasias (FCDs) are malformations of cortical development that often result in medically refractory epilepsy, with a greater incidence in the pediatric population. The relationship between the disturbed cortical morphology and epileptogenic activity of FCDs remains unclear. We used the BCNU (carmustine 1-3-bis-chloroethyl-nitrosourea) animal model of cortical dysplasia to evaluate neuronal and laminar alterations and how these result in altered activity of intracortical networks in early life. We corroborated the previously reported morphological anomalies characteristic of the BCNU model, comprising slightly larger and rounder neurons and abnormal cortical lamination. Next, the neuronal activity of live cortical slices was evaluated through large field-of-view calcium imaging as well as the neuronal response to a stimulus that leads to cortical hyperexcitability (pilocarpine). Examination of the joint activity of neuronal calcium time series allowed us to identify intracortical communication patterns and their response to pilocarpine. The baseline power density distribution of neurons in the cortex of BCNU-treated animals was different from that of control animals, with the former showing no modulation after stimulus. Moreover, the intracortical communication pattern differed between the two groups, with cortexes from BCNU-treated animals displaying decreased inter-layer connectivity as compared to control animals. Our results indicate that the altered anatomical organization of the cortex of BCNU-treated rats translates into altered functional networks that respond abnormally to a hyperexcitable stimulus and highlight the role of network dysfunction in the pathophysiology of cortical dysplasia.

Diabetes relacionada con la fibrosis quística / Cystic fibrosis-related diabetes

Los avances en el campo de la fibrosis quística han aumentado la esperanza de vida de estos pacientes, por lo que cada vez es más prevalente la Diabetes Relacionada con la Fibrosis Quística (DRFQ) y sus complicaciones. La DRFQ se asocia a mayor morbimortalidad, deterioro de la función pulmonar y del estado nutricional. Por lo mismo, el manejo óptimo de esta patología depende de un diagnóstico precoz, tratamiento individualizado y vigilancia de las complicaciones diabéticas. El screening de DRFQ debe realizarse anualmente a partir de los 10 años, mediante una Prueba de Tolerancia a la Glucosa Oral (PTGO), lo cual permite el diagnóstico. El manejo de esta patología tiene por objetivo estabilizar y mejorar la función pulmonar y el estado nutricional y metabólico de los pacientes. Actualmente, la insulina es el tratamiento farmacológico de elección para controlar la hiperglicemia y el esquema de uso debe ser individualizado para cada persona. En caso de enfermedades agudas pueden existir mayores requerimientos de insulina. Además, se deben tener consideraciones especiales en cuanto a la dieta y la insuficiencia pancreática exocrina que presentan estos pacientes. Para la vigilancia de complicaciones microvasculares se debe realizar una monitorización anual a partir de los 5 años desde el diagnóstico de DRFQ. Debido a la complejidad de estos pacientes, para alcanzar el mejor cuidado posible se necesita un enfoque multidisciplinario con distintos profesionales de la salud coordinados, incluyendo en la toma de decisiones al paciente y su familia.

Advances made in the field of cystic fibrosis have increased the life expectancy of these patients, which is why Cystic Fibrosis-Related Diabetes (CFRD) and its complications are becoming more and more prevalent. CFRD is associated with increased morbidity and mortality, lower lung function and inadequate weight maintenance. Therefore, the optimal management of this pathology depends on an early diagnosis, individualized treatment and monitoring of diabetic complications. For CFRD, routine screening with an Oral Glucose Tolerance Test (OGTT) should be carried out yearly from the age of 10, which allows to diagnose it. The treatment goals in CFRD are to stabilize and improve lung function and obtain adequate weight gain. Currently, insulin is the pharmacological treatment of choice to control hyperglycemia and the insulin regimen must be personalized for each person. In acute illnesses, there may be higher insulin requirements. In addition, special considerations must be taken regarding diet and exocrine pancreatic insufficiency that these patients present. For the surveillance of microvascular complications, annual monitoring should be carried out 5 years after the diagnosis of CFRD. Due to the complexity of these patients, in order to achieve the best possible care, a multidisciplinary approach is needed with different coordinated health professionals, including the patients and their family in the decision-making process.

Carcinoma epidermoide infiltrante en cara en paciente con antecedente de Leishmaniasis cutánea: Reporte de un caso / Squamous cell carcinoma infiltrated face in patient with history of cutaneous Leishmaniasis: A case report

Las leishmaniasis son enfermedades causadas por parásitos, se clasifican en: cutánea restringido a la piel, forma mucocutánea y visceral. Se ha reportado la asociación de la leishmaniasis con cambios neoplásicos, como el carcinoma epidermoide. El carcinoma epidermoide se caracteriza por una proliferación de queratinocitos atípicos, siendo un factor predisponente las lesiones crónicas. Presentamos el caso de un varón de 48 años, que desarrolló carcinoma epidermoide en la zona de la lesión primaria, de leishmaniasis cutánea.

The leishmaniasis is a disease caused by parasites, is classified as cutaneous, mucocutaneous and visceral. It has been reported leishmaniasis association with neoplastic changes, as squamous cell carcinoma. Squamous cell carcinoma is characterized by a proliferation of atypical keratinocytes, being a predisposing factor chronic lesions. We report a case of a 48 year old male, that squamous cell carcinoma development at the site of primary lesion, of mucocutaneous leishmaniasis.

[Ketosis prone type 2 diabetes (KPD)]. / Diabetes Mellitus tipo 2 con tendencia a la cetosis: Caso clínico.

Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations.

Diabetes Mellitus tipo 2 con tendencia a la cetosis: Caso clínico / Ketosis prone type 2 diabetes (KPD)

Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations.

Child overweight and obesity are associated with reduced executive cognitive performance and brain alterations: a magnetic resonance imaging study in Mexican children.

BACKGROUND: Overweight and obesity in childhood is associated with negative physical and psychological effects. It has been proposed that obesity increase the risk for developing cognitive deficits, dementia and Alzheimer's disease and that it may be associated with marked differences in specific brain structure volumes. OBJECTIVE: The purpose of this study was a neurobiopsychological approach to examine the association between overweight and obesity, brain structure and a paediatric neuropsychological assessment in Mexican children between 6 and 8 years of age. METHODS: We investigated the relation between the body mass index (BMI), brain volumetric segmentation of subcortical gray and white matter regions obtained with magnetic resonance imaging and the Neuropsychological Assessment of Children standardized for Latin America. Thirty-three healthy Mexican children between 6 and 8 years of age, divided into normal weight (18 children) and overweight/obese (15 children) groups. RESULTS: Overweight/obese children showed reduced executive cognitive performance on neuropsychological evaluations (i.e. verbal fluidity, P = 0.03) and presented differences in brain structures related to learning and memory (reduced left hippocampal volumes, P = 0.04) and executive functions (larger white matter volumes in the left cerebellum, P = 0.04 and mid-posterior corpus callosum, P = 0.03). Additionally, we found a positive correlation between BMI and left globulus pallidus (P = 0.012, ρ = 0.43) volume and a negative correlation between BMI and neuropsychological evaluation scores (P = 0.033, ρ = -0.37). CONCLUSIONS: The findings contribute to the idea that there is a relationship between BMI, executive cognitive performance and brain structure that may underlie the causal chain that leads to obesity in adulthood.

Alteraciones hematológicas en la diabetes mellitus / Blood disorders in diabetes mellitus

Although it has been treated in a limited way the relationship between diabetes and hematopoietic system, there is evidence demonstrating thedeleterious effect of hyperglycemia on the three cell lines: red blood cells, white cells and platelets. Different forms of anemia associated with hyperglycemia are analyzed and erythrocyte alterations observed in diabetes. In chronic decompensated patients have been demonstrated alterationsof monocytes, lymphocytes and polymorphonuclear particularly, with decreased chemotaxis, adherence, phagocytosis and opsonization. Hyperglycemia determines a prothrombotic state by platelet hyperreactivity, which is a marker of inflammation...

Diabéticos tipo 1 portadores de síndrome metabólico: cuantificación de la resistencia a la insulina / Type 1 diabetics patients carriers of metabolic syndrome: quantification of insulin resistance

The presence of insulin resistance (IR) has been indirectly assessed in Type 1 Diabetics (T1DM) through the detection of Metabolic Syndrome (MS), by applying criteria for Type 2 Diabetics(T2DM). In the EDC study (the Pittsburg Epidemiology of Diabetes Complications) a formula applicable to T1DM was validated, quantifying IR through the glucose uptake (GU) employing the usual clinical and laboratory parameters, in patients with HbA1c < 11.4 percent. Objectives: To determine in T1DM whether there exists a relationship between the presence of MS according to the Modified NCEP/ATPIII criteria and IR quantification through assessment of the glucose uptake or GU. Patients and Method: The modified NCEP/ATPIII criteria were applied to 150 T1DM patients, and those with more than 3 altered parameters were classified as MS carriers. IR was quantified through the glucose uptake (GU), applying the formula for Estimated Glucose Disposal Rate (GDR-EDC). Results: 26.6 percent of the T1DM (40 patients) complied with the modified NCEP/ATPIII criteria. When the formula for GU was applied (31 patient), 90.3 percent of the T1DM showed insulin resistance (GU value < 8.77). And when applied to 124 patients (T1DM with and without MS and HbA1c < 11,4 percent) 75 percent showed IR...

A macroscopic view of microstructure: using diffusion-weighted images to infer damage, repair, and plasticity of white matter.

Since its introduction in the early 1990s, diffusion-weighted magnetic resonance imaging (MRI) has played a crucial role in the non-invasive evaluation of tissue microstructure of brain parenchyma in vivo. Diffusion anisotropy, in particular, has been extensively used to infer histological changes due to brain maturation and pathology, as it shows a clear dependence on tissue architecture. Although the resolution used in most studies lies in the macroscopic range, the information provided originates at the microscopic level and, as such, diffusion MRI serves as a microscope that can reveal profound details of tissue with direct clinical and research applications. The interpretation of diffusion parameters of white matter rests on what is known to drive diffusion anisotropy, namely axonal membranes, density and coherence, as well as myelin sheaths. However, these factors interact to modulate anisotropy, making interpretations potentially difficult. While there are numerous publications that report diffusion changes in response to particular, histologically confirmed tissue abnormalities in animal models of disease, the microscopic correlates of altered diffusion parameters due to neurological disorders in humans have been difficult to characterize. Animal models may provide insight into the mechanisms involved, but do not necessarily provide accurate representations of the human condition, making human diffusion MRI studies with direct histological confirmation crucial for our understanding of tissue changes secondary to neurodevelopment and disease. This work provides a synopsis of tissue characteristics that give rise to highly informative, specific diffusion patterns, and also of how methodological and artifactual aspects can provide erroneous diffusion measurements that do not accurately reflect tissue and may lead to misinterpretation of results. Examples of diffusion changes due to human conditions are provided to illustrate the wealth of applications of diffusion MRI in clinical and research fields.

Intensidad de movimiento de escolares durante clases de educación física de colegios municipales: resultados según el profesional que efectúa las clases / Movement intensity of children during physical education classes in public schools: results according to the type of professional that teaches the class

Las clases de educación física debieran contribuir a aumentar el gasto energético incluyendo actividades de intensidad moderada/vigorosa (AIMI) equivalentes al 50% de la clase. Se determinó el tiempo que destinan escolares a AIMI durante una clase de educación física, identificando si existen diferencias según el tipo de docente que efectúa la clase y el estado nutricional de los ninos. La muestra incluyó 549 ninos de 6-8 anos de 8 escuelas municipales. Se realizaron mediciones antropométricas y tiempo en AIMI durante una clase de educación física utilizando podómetros. La proporción de clase que correspondió a AIMI fue de 15,8% y 12,9 % en varones y ninas respectivamente, sin diferencia por estado nutricional. Si la clase fue efectuada por especialista, ésta fue 16,9% y 14,2% y por el unidocente, 13,7 % y 10,8% en varones y ninas respectivamente. Se observaron diferencias por sexo y según el tipo de profesor, pero no por estado nutricional. La proporción de AIMI en la clase de educación física es sumamente baja, muy lejos de la recomendación de que sea 50% de la clase. El curriculum escolar debiera estar enfocado hacia actividades de mayor gasto energético y en lo posible quienes estén a cargo de la asignatura sean especialistas.

Physical education (PE) classes should contribute to increase daily energy expenditure, including moderate/ vigorous activities (MVA) during 50% ofthe class. We determined the % time in MVA during one PE class, identifying ifthere were differences according to the type of teacher in charge and the nutritional status of the children. The sample included 549 children 6 to 8 years old attending 8 public schools. Anthropometry and time in MVA were determined (usingpedometers). 15.8% and 12.9% of the PE class corresponded to MVA in boys and girls respectively, with no difference by nutritional status. If the class was taught by a PE teacher, 16.9% and 14.2% corresponded to MVA; if it was taught by the classroom teacher, it was 13.7% and 10.8% in boys and girls respectively. There were differences by sex and type of teacher, but not by nutritional status. The proportion of MVA during PE classes is much lower than the recommendation of 50% of the duration of the class. The curriculum should incorporate significantly more moderate/vigorous activities and if possible classes should be taught by PE teachers.

White-matter diffusion abnormalities in temporal-lobe epilepsy with and without mesial temporal sclerosis.

BACKGROUND: Although epilepsy is considered a grey-matter disorder, changes in the underlying brain connectivity have important implications in seizure generation and propagation. Abnormalities in the temporal and extratemporal white matter of patients with temporal-lobe epilepsy (TLE) and mesial temporal sclerosis (MTS) have previously been identified. Patients with TLE but without MTS often show a different course of the disorder and worse surgical outcome than patients with MTS. The purpose of this study was to determine if said white-matter abnormalities are related to the presence of MTS or if they are also present in non-lesional TLE. METHODS: Seventeen patients with TLE and MTS (TLE+uMTS), 13 patients with non-lesional TLE (nl-TLE) and 25 controls were included in the study. Diffusion tensor imaging (DTI) was used to assess tract integrity of the fornix, cingulum, external capsules and the corpus callosum. RESULTS: The white-matter abnormalities seen in the fornix appear to be exclusive to patients with MTS. Although the cingulum showed an abnormally high overall diffusivity in both TLE groups, its anisotropy was decreased only in the TLE+uMTS group in a pattern similar to the fornix. The frontal and temporal components of the corpus callosum, as well as the external capsules, demonstrated reduced anisotropy in TLE regardless of MTS. CONCLUSIONS: While some white-matter bundles are affected equally in both forms of TLE, abnormalities of the bundles directly related to the mesial temporal structures (ie, the fornix and cingulum) appear to be unique to TLE+uMTS.

[Ventricular tachycardia in a patient with mid-ventricular hypertrophic myocardiopathy and apical aneurysm]. / Taquicardias ventriculares sostenidas en un paciente con miocardiopatía hipertrófica medioventricular y aneurisma apical.

A case is presented of a 77-year-old patient who was admitted with a pattern of sustained ventricular tachycardia and diagnosed with midventricular hypertrophic myocardiopathy with apycal aneurysm. Under treatment with amiodarone at low doses, the patient is asymptomatic with no recurrence of the arrhytmias at one year. The association of midventricular hypertrophic myocardiopathy with apycal aneurysm and of those with sustained ventricular tachycardia are reviewed in conjunction with their treatment.

[The rupture of a cardiac hydatid cyst located in the right ventricle]. / Rotura de un quiste hidatídico cardíaco situado en ventrículo derecho.

Heart involvement in echinococcal disease is rare, but it is more infrequent the location of cysts in the right ventricle. We report a case of a male 35 years old with hydatid cysts located in the right ventricle. The condition was diagnosed by two-dimensional echocardiogram performed after the rupture of the cysts leading to massive pulmonary embolism and subsequently right heart failure. Early diagnosis appears mandatory in an attempt to modify, applying the appropriate therapy, the natural evolution of this potentially lethal condition.

Absorption and disposition kinetics of lithium carbonate following administration of conventional and controlled release formulations.

The absorption and disposition kinetics of lithium carbonate administered to eight healthy volunteers in two dosage forms were studied. A conventional immediate release tablet and a controlled release preparation, developed in our laboratory and containing the drug into a hydrophilic matrix, were employed in the study. Lithium carbonate confers upon the body the distinct characteristics of a two-compartment open model with a mean slow disposition rate constant (beta) of 0.0435 h-1 +/- 0.0086 SD, corresponding to a mean biological half-life of 16.49 h +/- 2.95 SD. The mean half-life of the distributory alpha-phase was 1.40 h +/- 0.27 SD. The apparent volume of distribution (Vdarea) was 0.539 l kg-1 +/- 0.130 SD and the volume of the central compartment (Vl) was 0.224 l/kg-1 +/- 0.066 SD, about one half that of the volume at steady state (Vdss) which was 0.445 l/kg-1 +/- 0.106 SD. Total body clearance (ClB) was 0.0241 l/kg-1 h +/- 0.0102 SD. The administration of the controlled release preparations to the same subjects gave the expected smooth serum lithium concentration curves. Maximum serum concentration (Cmax) was 22% lower and the time at which this concentration was attained (tpeak) was delayed from 1.44 h to 4.25 h when compared with the conventional tablet. Bioavailability, estimated as the total amount of lithium excreted in the urine, was 90.2 for the controlled release preparation and 94.5 for the immediate release tablet.