Evaluación del perfil de seguridad del medicamento tocilizumab en pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug tocilizumab in patients suspected or confirmed by COVID-19

Introducción: La enfermedad de COVID-19, es una enfermedad emergente cuya patogénesis se relaciona con la tormenta de citocina, la interleucina 6 juega un papel importante en la tormenta de citocinas. El medicamento tocilizumab, es un anticuerpo monoclonal humanizado, el cual se une al receptor soluble IL-6. En pacientes con COVID-19 se ha observado que el uso de tocilizumab disminuye la inflamación exacerbada. Ante este nuevo uso del medicamento es relevante establecer el balance beneficio-riesgo en estos pacientes con COVID-19, identificando con ello las reacciones adversas a medicamentos que pueden estar relacionadas al uso de tocilizumab. Materiales y métodos: Estudio de farmacovigilancia descriptivo y transversal en una cohorte retrospectiva en pacientes sospechosos o confirmados por COVID-19 en el Instituto Nacional de Cardiología Ignacio Chávez de la Ciudad de México, México en el periodo 05 de mayo del 2020 al 20 de enero del 2021. Resultados: De los 36 pacientes participantes en este estudio, la edad promedio fue 53 años, de los cuales 30 fueron hombres y 6 fueron mujeres. Las comorbilidades identificadas en este estudio fue la hipertensión arterial sistémica, seguida de la diabetes mellitus tipo II. En la evaluación de los estudios de laboratorio se observó que 2 pacientes desarollaron neutropenia moderada, mientras que en 5 pacientes se identificó trombocitopenia leve y 2 pacientes desarrollaron trombocitopenia moderada. Las infecciones bacterianas identificadas en el estudio con el uso del medicamento fueron: 5 aislamientos de Klebsiella oxytoca, 4 a Escherichia coli y 4 a Pseudomonas aeruginosa... (AU)

Introduction: COVID-19 is a new emerging disease which pathogenesis is mediated by a cytokines storm, interleukin 6 plays an important part of this storm. Tocilizumab is a humanized monoclonal antibody that binds to the IL-6 receptor. In patient with COVID-19, exacerbated inflammation has been observed to decrease when given tocilizumab. Due to the new use of this drug is relevant to stablish the risk-benefit ratio in COVID-19 patients, by identifying the drug adverse reactions that may be related to the use of tocilizumab. Material and methods: Descriptive and cross-sectional pharmacovigilance study in a retrospective cohort in patients suspected or confirmed by COVID-19 in the National Institute of Cardiology in Mexico City, Mexico from May 5, 2020 to January 20, 2021. Outcomes: From 36 patients in this study, the average age was 53 years of which 30 were men and 6 were women. The comorbidities identified in this study were systemic arterial hypertension followed by type II diabetes mellitus. Evaluating the laboratory results we observed 2 patients developed moderate neutropenia, 5 patients presented mild thrombocytopenia and 2 patients moderate thrombocytopenia. The bacterial infections identified in the study with the use of the tocilizumab were: 5 isolates Klebsiella oxytoca, 4 isolates Escherichia coli and 4 Pseudomonas aeruginosa. Conclusion: Knowing the possible drug adverse reactions that occurred in patients with COVID-19 who were administered tocilizumab, allow us to the identify the risks associated with the drug, determining the safety profile and be alert of bacterial infections, neutropenia, and thrombocytopenia, throughout a pharmacotherapeutical follow up, thereby identifying possible associated alterations possibly restated with the use of tocilizumab. (AU)

Corticosteroid safety in COVID-19 patients: a pharmacovigilance study / Seguridad de corticoesteroides en pacientes con COVID-19: un estudio de farmacovigilancia

The use of oral and intravenous corticosteroids as a treatment for SARS-CoV-2 infection has been shown to inhibit the exaggerated inflammatory response, reducing symptoms and days of hospitalization of patients. However, its use is controversial because not enough clinical studies have been made to verify the safety of the drugs. Objective: To assess the safety profile of corticosteroids treatment, at high and low doses, in suspected or confirmed patients with COVID-19, determining the most frequent side effects in patients, and assessing whether the administration of the drugs represents a greater benefit than the risk of presenting these effects. Methods: Ambispective study of active pharmacovigilance at a cohort of confirmed or suspected COVID-19 patients, treated with intravenous and oral corticosteroids. 366 patients were evaluated and divided into 3 groups: use of methylprednisolone (155 mg average) every 24 hours for 3 days, dexamethasone (6 mg) every 24 hours for 10 days, and a control group. Results: The distribution of the cases with hyperglycemia was 33 in high doses and 82 with low doses of corticosteroids and both high and low doses have a similar distribution in cases of infections. When evaluating the harshness and severity of hyperglycemia in the two groups with corticosteroids, it is observed that patients with high doses present more harsh (48%). In case of harshness and severity of infections it is observed that patients with high doses present more harsh (62%) and more severe (79%) cases than those who were administered low doses. (AU)

El uso de corticoides orales e intravenosos como tratamiento para la infección por SARS-CoV-2 ha demostrado inhibir la respuesta inflamatoria exagerada, reduciendo los síntomas y los días de hospitalización de los pacientes. Sin embargo, su uso es controvertido porque no se han realizado suficientes estudios clínicos para verificar la seguridad de los medicamentos. Objetivo: Evaluar el perfil de seguridad del tratamiento con corticoides, a dosis altas y bajas, en pacientes con sospecha o confirmación de COVID-19, determinando los efectos secundarios más frecuentes en los pacientes, y valorando si la administración de los fármacos representa un mayor beneficio que el riesgo de presentar estos efectos. Métodos: Estudio ambispectivo de farmacovigilancia activa en una cohorte de pacientes confirmados o sospechosos de COVID-19, tratados con corticoides intravenosos y orales. Se evaluaron 366 pacientes y se dividieron en 3 grupos: uso de metilprednisolona (155 mg promedio) cada 24 horas por 3 días, dexametasona (6 mg) cada 24 horas por 10 días y un grupo control. Resultados: La distribución de los casos con hiperglucemia fue de 33 casos usando dosis altas y 82 con dosis bajas de corticoides, tanto las dosis altas como las bajas tienen la misma distribución en los casos de infecciones. Al evaluar la severidad y gravedad de la hiperglucemia en los dos grupos con corticoides, se observa que los pacientes con dosis altas presentan mayor gravedad (48%). En caso de severidad y gravedad de las infecciones se observa que los pacientes con dosis altas presentan casos más graves (62%) y más severos (79%) que los que recibieron dosis bajas. (AU)

Características clínicas de la coriorretinopatía exudativa hemorrágica periférica en un centro de referencia en España / Clinical characteristics of peripheral exudative hemorrhagic chorioretinopathy in a referral center in Spain

Objetivo: Publicar las características clínicas de la coriorretinopatía exudativa hemorrágica periférica (CEHP) en la población española. Métodos: Estudio retrospectivo y análisis de los resultados en pacientes con diagnóstico de CEHP. Fueron recogidas las características clínicas, por OCT, el tratamiento utilizado y la evolución posterior al tratamiento. Resultados: Se evaluaron 39 ojos de 23 pacientes con CEHP. La edad promedio al diagnóstico fue de 79 años (66-94 años). El síntoma ocular principal fue la disminución de visión en 26 ojos (66,6%), siendo 11 ojos (28,2%) asintomáticos. El diagnóstico de referencia más frecuente fue sangrado/exudación en 24 ojos (61,5%), le siguió melanoma coroideo con 9 (23,1%). Las hemorragias intra o subretinianas fueron el tipo de lesión periférica más frecuentemente encontrado, en 24 ojos (61,5%). Veinticinco ojos (58,9%) recibieron algún tipo de tratamiento: A 15 ojos (60%) se les realizó inyección intravítrea (IIV) de antioangiogénicos (anti-VEGF); se realizó fotocoagulación con láser en 2 casos (8%), terapia fotodinámica en 2 casos (8%) y 6 casos (18,2%) precisaron vitrectomía vía pars plana (VPP) por hemorragia vítrea. No hubo cambios en la agudeza visual (AV) en los pacientes seguidos con observación entre el inicio 0,66±0,80 (0,04-2,82) y el fin de seguimiento 0,75±0,96 (0,00-2,82) (p=0,352), ni para los que recibieron algún tipo de tratamiento entre inicio 0,78±0,79 (0,04-2,30) y fin 1,22±1,01 (0,04-2,82) (p=0,157), posiblemente debido al gran componente de degeneración macular asociada con la edad (DMAE) atrófica o exudativa presente en ambos grupos (29 ojos presentaron DMAE atrófica o exudativa). Conclusiones: La CEHP es una enfermedad poco frecuente, asociada frecuentemente con DMAE, que se presenta típicamente como una masa periférica que se confunde frecuentemente con melanoma...(AU)

Objective: To publish the clinical characteristics of peripheral exudative hemorrhagic chorioretinopathy (PHEC) in the Spanish population. Methods: Retrospective study and analysis of results in patients diagnosed with PHEC. The clinical characteristics, by OCT, the treatment used and the evolution after treatment were collected. Results: 39 eyes of 23 patients with PHEC were evaluated. The average age at diagnosis was 79 years (66-94 years). The main ocular symptom was low vision in 26 eyes (66.6%); only 11 eyes (28.2%) were asymptomatic. The most frequent referred diagnosis was bleeding/exudation in 24 eyes (61.5%), followed by choroidal melanoma in 9 (23.1%). Intra or subretinal hemorrhages were the type of peripheral lesion most frequently found, in 24 eyes (61.5%). Twenty-five eyes (58.9%) received some type of treatment: 15 eyes (60%) underwent intravitreal injection (IIV) of antiangiogenic agents (anti-VEGF); Laser photocoagulation was performed in 2 cases (8%), Photodynamic therapy in 2 cases (8%) and 6 cases (18.2%) required pars plana vitrectomy (PPV) due to vitreous hemorrhage. There were no changes in visual acuity (VA) in patients followed with observation between baseline 0.66±0.80 (0.04-2.82) and end of follow-up 0.75±0.96 (0.00-2.82) (P=.352), nor for those who received some type of treatment between the beginning 0.78±0.79 (0.04-2.30) and the end 1.22±1.01 (0.04-2.82) (P=.157), possibly due to the large component of atrophic or exudative age-related macular degeneration (AMD) presented in both groups. (29 eyes presented atrophic or exudative AMD). Conclusions: PHEC is a rare pathology, frequently associated with AMD, which typically presents as a peripheral mass that is frequently confused with choroidal melanoma and other intraocular tumors and hence the importance of learning to identify it, making the correct differential diagnosis and avoid unnecessary treatments. Antiangiogenic therapy is effective in most patients with...(AU)

Clinical characteristics of peripheral exudative hemorrhagic chorioretinopathy in a referral center in Spain.

OBJECTIVE: To publish the clinical characteristics of peripheral exudative hemorrhagic chorioretinopathy (PHEC) in the Spanish population. METHODS: Retrospective study and analysis of results in patients diagnosed with PHEC. The clinical characteristics, by OCT, the treatment used and the evolution after treatment were collected. RESULTS: 39 eyes of 23 patients with PHEC were evaluated. The average age at diagnosis was 79 years (66-94 years). The main ocular symptom was low vision in 26 eyes (66.6%); only 11 eyes (28.2%) were asymptomatic. The most frequent referred diagnosis was bleeding/exudation in 24 eyes (61.5%), followed by choroidal melanoma in 9 (23.1%). Intra or subretinal hemorrhages were the type of peripheral lesion most frequently found, in 24 eyes (61.5%). Twenty-five eyes (58.9%) received some type of treatment: 15 eyes (60%) underwent intravitreal injection (IIV) of antiangiogenic agents (anti-VEGF); Laser photocoagulation was performed in 2 cases (8%), Photodynamic therapy in 2 cases (8%) and 6 cases (18.2%) required pars plana vitrectomy (PPV) due to vitreous hemorrhage. There were no changes in visual acuity (VA) in patients followed with observation between baseline 0.66±0.80 (0.04-2.82) and end of follow-up 0.75±0.96 (0.00-2.82) (P=.352), nor for those who received some type of treatment between the beginning 0.78±0.79 (0.04-2.30) and the end 1.22±1.01 (0.04-2.82) (P=.157), possibly due to the large component of atrophic or exudative age-related macular degeneration (AMD) presented in both groups. (29 eyes presented atrophic or exudative AMD) CONCLUSIONS: PHEC is a rare pathology, frequently associated with AMD, which typically presents as a peripheral mass that is frequently confused with choroidal melanoma and other intraocular tumors and hence the importance of learning to identify it, making the correct differential diagnosis and avoid unnecessary treatments. Antiangiogenic therapy is effective in most patients with an active phase (exudative/hemorrhagic) into leading to fibrosis of peripheral hemorrhagic areas.

Evaluación del perfil de seguridad del medicamento lopinavir/ritonavir (Lpv/r) en los pacientes sospechosos o confirmados por COVID-19 / Evaluation of the safety profile of the drug lopinavir/ritonavir (Lpv/r) in suspected or confirmed COVID-19 patients

Introducción: El nuevo SARS-CoV-2, es el agente causal de la enfermedad COVID-19. La Organización Mundial de la Salud (OMS) ha referenciado el uso del lopinavir/ritonavir (Lpv/r), es un inhibidor de la proteasa del virus de inmunodeficiencia humana adquirida (VIH-1). El estudio clínico de Cao et al., identificó que el uso de Lpv/r no se asociaron con un mayor número de eventos adversos en comparación con el tratamiento estándar.Materiales y métodos: Estudio retrospectivo de farmacovigilancia en una cohorte en pacientes sospechosos o confirmados de COVID-19 en un hospital de tercer Nivel de la Ciudad de México en el periodo 01 abril 2020 al 30 julio 2020. Resultados: El tratamiento de Lpv/r incluyó 140 pacientes, de los cuales 91 pacientes completaron el tratamiento, mientras que 50 pacientes no terminaron el esquema. Los principales motivos de la suspensión del esquema del medicamento fueron: alta por mejoría (11 casos), defunciones (10 casos) y por inicio de ruxolitinib (9 casos). Además, se identificaron 8 reacciones adversas al medicamento, de las cuales 5 son reacciones asociadas a los trastornos gastrointestinales (diarreas) y las otras 3 reacciones asociadas a trastornos hepatobiliares (hipertransaminasemia).Conclusión: El perfil de seguridad del medicamento Lpv/r demostró una coherencia con las observaciones de estudios previos en relación en los eventos adversos presentados de tipo gastrointestinales y hepáticos, estos últimos se encuentran relacionados a interacción fármaco-fármaco, por lo que sugerimos un seguimiento farmacoterapéutico para identificar las interacciones y las reacciones adversas durante el uso Lpv/r. (AU)

Abstract: The new SARS-CoV-2 is the causal agent for COVID-19. The World Health Organization (WHO) referenced the use of lopinavir/ritonavir (Lpv/r), which is a protease inhibitor of human inmunodeficiency virus (HIV-1). The Clinical trial by Cao et al. identified that the use of Lpv/r has not been associated with any increase of adverse drug reactions within compared to the standard of care.Materials and methods: Pharmacovigilance retrospective study of patients suspected or confirmed with COVID-19 in a 3rd level hospital in Mexico City from April, 01 2020 to July, 30 2020.Results: Lopinavir/ritonavir treatment was prescribed 140 patients from which 91 patients completed the treatment, while 50 patients did not completed the treatment. The cause suspensions were: patient discharge for improvement (11 cases), deaths (10 cases) and start of ruxolitinib (9 cases). In addition, were identify 8 adverse drug reaction from which 5 were associated to gastrointestinal disorders (diarrhea) and 3 hepatobiliary disorders (hypertransaminasemia).Conclusion: The safety profile of the Lpv/r demonstrated consistency with the observations of previous studies in relation to gastrointestinal and hepatic adverse events, which were related to drug-drug interaction, so we suggest a pharmacotherapeutic monitoring to identify them as well as adverse drug reactions due to Lpv/r. (AU)

Agreement and differences between macular values in children using two types of spectral optical coherence tomography.

OBJECTIVES: To determine the degree of agreement and differences between macular parameters according to sex, age, laterality, ethnicity and type of optical coherence tomography (OCT) in paediatric patients. MATERIALS AND METHODS: Prospective, transversal, and comparative study. OCT Spectralis and OCT Cirrus were used to obtain the macular values of both eyes in 100 patients between 5 and 15 years without ocular pathology. Due to the similarity between the values of both eyes, in the final sample we only considered the right eyes (OD) (n = 100). RESULTS: The average central macular thickness (CMT) was 244.2 µm with Cirrus and 261.7 µm with Spectralis. The degree of agreement for the GMC was moderate (Intraclass Correlation Coefficient: 0.66) and from low to very low in the other quadrants. The GMC values of both systems were significantly higher in men than in women (P < .05). The macular retinal nerve fibre layer (mRNC), ganglion cell layer (GCC), the inner plexiform layer (IPLC), and the inner nuclear layer (INFL) had significantly higher values in men than in women (P < .01). There were no statistically significant differences in the GMC by age and laterality, however it was significantly higher in ethnic European children than in ethnic Latin American children; Cirrus (P = .042) and Spectralis (P = .033). CONCLUSIONS: Macular parameters obtained by OCT Spectralis and OCT Cirrus should not be interchangeable in pediatric patients.

Grado de concordancia y diferencias entre valores maculares en niños mediante dos tipos de tomografía de coherencia óptica espectral / Agreement and differences between macular values in children using two types of spectral optical coherence tomography

Objetivo Determinar el grado de concordancia y las diferencias entre los parámetros maculares en función de sexo, edad, lateralidad, etnia y tipo de tomografía de coherencia óptica (OCT) en pacientes pediátricos. Materiales y métodos Estudio prospectivo, transversal y comparativo. Se hizo uso de la OCT Spectralis y la OCT Cirrus para obtener los valores maculares de ambos ojos en 100 pacientes entre 5 y 15años sin patología ocular. Debido a la semejanza entre los valores de ambos ojos, en la muestra final solo consideramos los ojos derechos (OD) (n=100). Resultados La media del grosor macular central (GMC) fue de 244,2μm con Cirrus y 261,7μm con Spectralis. El grado de concordancia para el GMC fue moderado (coeficiente de correlación intraclase: 0,66) y de bajo a muy bajo en el resto de cuadrantes. Los valores de GMC de ambos sistemas fueron significativamente mayores en varones que en mujeres (p<0,05). La capa de fibras nerviosas de la retina macular (CFNRm), la capa de células ganglionares (CCG), la capa plexiforme interna (CPI) y la capa nuclear interna (CNI) tuvieron valores significativamente mayores en varones que en mujeres (p<0,01). No hubo diferencias estadísticamente significativas en el GMC según edad y lateralidad; sin embargo, fue significativamente mayor en niños de etnia europea que en niños de etnia latinoamericana; Cirrus (p=0,042) y Spectralis (p=0,033). Conclusiones Los parámetros maculares obtenidos mediante OCT Spectralis y OCT Cirrus no deberían ser intercambiables en pacientes pediátricos (AU)

Objective To determine the degree of agreement and differences between macular parameters according to sex, age, laterality, ethnicity and type of optical coherence tomography (OCT) in paediatric patients. Materials and methods Prospective, transversal, and comparative study. OCT Spectralis and OCT Cirrus were used to obtain the macular values of both eyes in 100 patients between 5 and 15years without ocular pathology. Due to the similarity between the values of both eyes, in the final sample we only considered the right eyes (OD) (n=100). Results The average central macular thickness (CMT) was 244.2μm with Cirrus and 261.7μm with Spectralis. The degree of agreement for the GMC was moderate (intraclass correlation coefficient: 0.66) and from low to very low in the other quadrants. The GMC values of both systems were significantly higher in men than in women (P<.05). The macular retinal nerve fibre layer (mRNC), ganglion cell layer (GCC), the inner plexiform layer (IPLC), and the inner nuclear layer (INFL) had significantly higher values in men than in women (P<.01). There were no statistically significant differences in the GMC by age and laterality, however it was significantly higher in ethnic European children than in ethnic Latin American children; Cirrus (P=.042) and Spectralis (P=.033). Conclusions Macular parameters obtained by OCT Spectralis and OCT Cirrus should not be interchangeable in pediatric patients (AU)

[Progressive Brown-Sequard syndrome secondary to idiopathic spinal cord herniation: clinico-radiological and surgical correlations]. / Síndrome de Brown-Séquard progresivo secundario a hernia medular idiopática: correlación clinicorradiológica y quirúrgica.

INTRODUCTION: Idiopathic medullary herniation is an infrequent disease, which shows up in clinical form as a progressive mielopathy, most commonly known as the Brown-Sequard syndrome. Its anatomical base is a dural defect where a portion of anterior spinal cord gets progressively incarcerated. The MRI and myelo-CT scan show a bending of the spinal cord in the form of a «bell tent¼ towards the anterior dural sheath at the mid-dorsal portion mainly. CASE REPORT: A 37 year old male, who was diagnosed of idiopathic medullary herniation and surgically treated by our own developed technique, reporting its neuroradiological, anatomo-surgical and clinical correlation. CONCLUSION: Treatment should be individualized, as no standard surgical technique has been established up to the present.

TITLE: Síndrome de Brown-Séquard progresivo secundario a hernia medular idiopática: correlación clinicorradiológica y quirúrgica.Introducción. La hernia medular idiopática es una patología infrecuente que cursa clínicamente con una mielopatía progresiva, la mayoría de las ocasiones en forma de síndrome de Brown-Séquard. Su base anatómica es un defecto dural por el que se incarcera progresivamente una porción del cordón medular anterior. La resonancia magnética y la mielotomografía demuestran un acodamiento medular en «tienda de campaña¼ hacia la cara anterior del estuche dural, a nivel dorsal medio fundamentalmente. Caso clínico. Varón de 37 años, diagnosticado de hernia medular idiopática e intervenido quirúrgicamente mediante una técnica propia; se demuestra su correlación neurorradiológica, anatomoquirúrgica y evolutiva. Conclusión. El tratamiento debe ser individualizado, pues no existe una técnica quirúrgica universalmente establecida.

Agreement in retinal nerve fiber layer values and comparison in children using two optical coherence tomography devices. / Grado de concordancia y diferencias entre los valores de capa de fibras nerviosas de la retina peripapilar en niños mediante dos tipos de tomografía de coherencia óptica espectral.

OBJECTIVE: To assess absolute agreement and differences in peripapillary retinal nerve fiber layer (pRNFL) values according to sex, age, laterality, origin and optical coherence tomography (OCT) type in normal pediatric patients undergoing OCT scans using both Cirrus and Spectralis. MATERIAL AND METHODS: Prospective, cross-sectional, and comparative study. We used Spectralis OCT and Cirrus OCT to measure optic disc values of both eyes in one hundred pediatric patients (age 5 to 15years), with no previous ocular pathology or systemic disease that could affect the eye. Due to the similarity between eyes, only right eyes were considered (n=100). RESULTS: The average peripapillary retinal nerve fiber layer (pRNFL) values were 99.6µm with Cirrus and 106.7µm with the Spectralis system. The four quadrants followed the ISNT rule (inferior-superior-nasal-temporal). The average pRNFL measures correlated negatively with the AL (P<.01) in both OCTs, and the degree of agreement between OCTs for pRNFL and inferior RNFL was moderate (CCI: 0.67 and 0.61, respectively), and low in the rest of the sectors. The average pRNFL values of both OCTs were higher in women than in men (P>.05) and there were also no statistical differences in the pRNFL according to age or laterality (P>.05). All RNFL values were significantly different between both types of OCTs (P<.05) and average pRNFL values were significantly thicker (P<.05) in Latin American than in European children in both eyes. CONCLUSIONS: We suggest that the respective peripapillary RNFL values obtained using these two OCTs should not be considered interchangeable in pediatric patients.

Presurgical Identification of the Central Sulcus Using GE EPI Sequences in Combination with 3D Reconstruction is a Useful and Easy Technique for Functional Identification of the Sensorimotor Cortex.

Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging technique that enables the visualization of vascular changes originating in the cortex on the execution of a simple motor task. We aimed to assess the usefulness of sensorimotor fMRI using echo-planar imaging (EPI) techniques and assess its clinical usefulness in the identification of the central sulcus. We studied 32 candidates for neurosurgery who had centrally located space-occupying lesions with fMRI using EPI images with blood oxygen level-dependent (BOLD) gradient-echo (GE) sequences acquired on a 1.5T scanner while patients repeatedly opened and closed their hands. Statistical activation images (t images) corresponding to the movements of the right and left hands were compared using cancellation analysis. Three-dimensional reconstruction of the cranium and brain of each patient showed the relative position of the expansive lesion and of non-damaged cortical tissue. Reproducible and selective functional sensorimotor activation was observed in 32 patients. Validation was carried out by intraoperative mapping in 19 patients. Based on intraoperative confirmation data we assumed that functional MR imaging (fMRI) is a valid method for identifying the motor cortex. Nevertheless, a limitation to our study is that not all the patients received invasive cortical stimulation. It is also relevant to indicate that fMRI and intraoperative procedures coincide in the sulcus identified as the sensorimotor cortex. Neurological examination did not reveal postoperative motor/sensitive deterioration in the remaining patients. fMRI using GE EPI sequences in combination with three-dimensional reconstruction is a useful and easy technique for functional identification of the sensorimotor cortex.

Procyanidin dimer B1 and trimer C1 impair inflammatory response signalling in human monocytes.

The way specific procyanidins exert their anti-inflammatory effects is not fully understood. This study has investigated the capacity of different procyanidins to modulate lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) production in THP1 human monocytes and their effects on the redox regulated protein kinases activity: IkB kinase beta (IKKb) and the extracellular signal-regulated kinase (ERK). LPS-triggered increase of ROS was prevented by cell pre-incubation with procyanidins. LPS induced ERK1/2 activation through phosphorylation, which was inhibited by all the compounds tested, the most active being epigallocatechin (EG), followed by epigallocatechin gallate (EGCG) and C1. Procyanidins inhibited IKKb activity in vitro. C1 and procyanidin extract (PE) exerted the maximal IKKb inhibition, followed by EGCG and dimer B1. Catechin exerted a slight but significant IKKb inhibition, in contrast to epicatechin, which was ineffective. In conclusion, procyanidins reduce the LPS-induced production of ROS and they exert their anti-inflammatory effects by inhibiting ERK1/2 and IKKb activity.

Grape seed proanthocyanidins correct dyslipidemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver.

OBJECTIVE: To determine whether proanthocyanidins can protect against dyslipidemia induced by a high-fat diet (HFD) and to address the mechanisms that underlie this hypolipidemic effect. DESIGN AND MEASUREMENTS: Female Wistar rats were fed on a HFD for 13 weeks. They were divided into two groups, one of which was treated with a grape seed proanthocyanidin extract (25 mg kg(-1) of body weight) for 10 days. Plasma and liver lipids were measured by colorimetric and gravimetric analysis. Liver, muscle and adipose tissue were used to study the expression of genes involved in the synthesis and oxidation of fatty acids and lipoprotein homeostasis by real-time RT-PCR. RESULTS: The administration of proanthocyanidins normalized plasma triglyceride and LDL-cholesterol (both parameters significantly increased with the HFD) but tended to decrease hypercholesterolemia and fatty liver. Gene expression analyses revealed that proanthocyanidins repressed both the expression of hepatic key regulators of lipogenesis and very low density lipoprotein (VLDL) assembling such as SREBP1, MTP and DGAT2, all of which were overexpressed by the HFD. CONCLUSION: These findings indicate that natural proanthocyanidins improve dyslipidemia associated with HFDs, mainly by repressing lipogenesis and VLDL assembly in the liver, and support the idea that they are powerful agents for preventing and treating lipid altered metabolic states.

Comparison of culture-based methods to enumerate Escherichia coli in tropical and temperate freshwaters.

AIMS: The specificity of a method for the enumeration of Escherichia coli (chromocult agar, CC) was tested using freshwater samples from a tropical area (Cuba Island) by isolating colonies and identifying them with API (Appareillage et procédé d'identification) strips. Enumerations of E. coli by the most probable number (MPN) microplate method were compared with counts on chromogenic and fluorogenic agar media [CC, rapid E. coli (REC), fluorocult] in tropical and temperate freshwater samples. METHODS AND RESULTS: A high percentage of specificity (95.7%) for the CC agar enumeration of E. coli was observed. High regression coefficients (log-log linear regressions) were found between E. coli counts on agar media and by the MPN method. In the tropical environment, counts with REC medium were significantly different from those obtained with the other methods. MPN counts were found to be significantly higher than those obtained using the plate counts methods in the temperate environment. CONCLUSIONS: Escherichia coli enumeration methods based on glucuronidase activity appear to be suitable for the evaluation of microbiological quality in the tropical environment featured in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: The methods for the enumeration of E. coli tested in this study should help improve the evaluation of microbiological contamination of Cuban freshwaters.

Late outcome of Senning and Mustard procedures for correction of transposition of the great arteries.

OBJECTIVES: To evaluate late mortality and morbidity after an atrial switch procedure for correction of transposition of the great arteries (TGA) and to assess predictive factors for adverse outcome. SETTING: Tertiary referral centre. DESIGN AND PATIENTS: Retrospective follow up study of 137 patients surviving hospitalisation for TGA atrial switch procedure (Mustard or Senning) in a single institution and divided into two groups (simple and complex) depending on presurgical anatomy. Several surgical and follow up factors were evaluated during 16.7 (5.6) years' follow up. RESULTS: Late mortality was 5.1% (95% confidence interval 1.37% to 8.84%) with sudden death as the most common cause. No significant difference was found between Mustard and Senning procedures and between the complex and simple groups in terms of mortality. Independent predictive factors for late mortality were a history of supraventricular tachyarrhythmias and advanced New York Heart Association (NYHA) functional class during follow up. A very common finding was development of sinus node dysfunction (47.6%), which had no influence on mortality. There was little need for reintervention (5.1%) and relatively few cases of right ventricular systolic dysfunction (14.6%). During follow up, most patients (96.2%) were in NYHA functional class I-II. CONCLUSIONS: Overall long term outcomes of patients with atrial repair of TGA in the present era are encouraging in terms of late mortality and quality of life. Nevertheless, better outcomes may be offered through improved diagnostic methods for right ventricular function and better management of supraventricular tachyarrhythmias.

[Implementation of habituation theory to pulsatile somato-sounds (tinnitus): the heart valve prosthesis sound model]. / Aplicación de la teoría de la habituación a los somatosonidos (acúfenos) pulsátiles: el sonido protésico valvular como modelo.

OBJECTIVES: To evaluate the habituation process to mechanical heart valve prosthesis sound as a model to understand the pulsatile tinnitus or somatosound perception changes. STUDY DESIGN: Transversal descriptive. PATIENTS: One hundred and fifty patients referred to a University Hospital for one or two mechanical heart valve implantation. OUTCOME MEASURES: Questionnaire sent by mail for prosthesis sound loudness and interference in quality of life evaluation. Detection of factors related to habituation process development. RESULTS: Eighty three percent of the patients perceived their prosthesis sound continuously, while only a 17% showed high levels of annoyance. No significative differences in prosthesis type and localization were described. Anxiety was the most important factor for loudness increase. The average of visual analogical scales on sound loudness and annoyance showed mild values (3.7 and 1.9 respectively). CONCLUSIONS: Extensive medical counselling or tinnitus retraining therapy (TRT) program for most severe cases, are proposed for pulsatile tinnitus management when etiological treatment cannot be available.

The different (sur)faces of Rap1p.

The DNA-binding protein Rap1p fulfills many different functions in the yeast cell. It targets 5% of the promoters, acting both as a transcriptional activator and as a repressor, depending on the DNA sequence context. In addition, Rap1p is an essential structural component of yeast telomeres, where it contributes to telomeric silencing. Here we review the evidence indicating that Rap1p function is modulated by the precise architecture of the its binding site and its surroundings: long tracts of telomeric repeats for telomeric functions, specific sequences and orientation for maximal transcriptional activation, and specific DNA recognition sequences for complementary factors in other cases. Many of these functions are probably related to chromatin organization around Rap1p DNA binding sites, resulting from the very tight binding of Rap1p to DNA. We propose that Rap1p alters its structure to bind to different versions of its DNA binding sequence. These structural changes may modulate the function of Rap1p domains, providing different interacting surfaces for binding to specific co-operating factors, and thus contributing to the diversity of Rap1p function.

Síndromes depresivos asociados a deterioro cognitivo / Depressive syndromes associated to cognitive deterioration

La presencia de síntomas depresivos y cuadros depresivos clínicamente significativos es frecuente entre los pacientes con deterioro cognitivo. Las muestras clínicas indican que entre el 30-50 por ciento de los pacientes con deterioro cognitivo presentan síntomas depresivos. Los síntomas depresivos son una fuente importante de discapacidad funcional adicional a la causada por el deterioro cognitivo. Por otra parte, los pacientes de edad avanzada con episodios depresivos mayores sin demencia presentan habitualmente déficits cognitivos que también empeoran el funcionamiento general. Aunque los síntomas depresivos y el deterioro cognitivo pueden darse de forma independiente o coexistir sin aparente conexión, cada vez existen más datos que sugieren una correlación que pudiera llegar incluso a ser etiológica. El nihilismo terapéutico ha sido la reacción más frecuente ante estos cuadros. Sin embargo, los tratamientos específicos o sintomáticos han demostrado ser eficaces en el tratamiento de los síntomas depresivos de los pacientes con alteraciones cognitivas, mejorando de forma significativa el funcionamiento general de los mismos. (AU)

Trastornos afectivos: análisis de su comorbilidad en los trastornos psiquiátricos más frecuentes / Affective disorders: analysis of their comorbility in the more frequent psychiatric disorders

La comorbilidad se define por la presencia de dos o más enfermedades independientes en un mismo sujeto. En este trabajo se revisa la comorbilidad de los trastornos afectivos con otros trastornos mentales y se centra en los trastornos de ansiedad, esquizofrenia, dependencia de sustancias psicoactivas, trastornos de alimentación, trastornos de personalidad y trastornos obsesivo-compulsivos. Para ello hemos realizado una extensa revisión teniendo en cuenta numerosos estudios, así como diferentes orientaciones diagnósticas (categorial o dimensional). En general, la presencia de síntomas y/o trastornos afectivos en el contexto de otras patologías mentales es alta. Además la comorbilidad tiene una alta transcendencia en cuanto al pronóstico clínico (peor respuesta a los tratamientos, mayor persistencia sintomática, mayor tendencia a la cronicidad y mayor riesgo de mortalidad) y las consecuencias sociales (disminución del rendimiento laboral y mayor uso de recursos). No obstante, tenemos que tener en cuenta que el análisis de la comorbilidad de los trastornos afectivos en otros trastornos mentales es complejo y controvertido, no sólo por su alta frecuencia sino por la existencia de un solapamiento sintomático, la escasez de signos y síntomas patognomónicos, la variabilidad de los criterios diagnósticos, las diferencias metodológicas aplicadas así como la escasez de estudios longitudinales y prospectivos. (AU)