Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva / Pathogenic variant in the PCDH19 gene in a patient with epilepsy and cognitive disability

INTRODUCCIÓN: La asociación de casos familiares de epilepsia y discapacidad intelectual (DI) en mujeres fue reportada en 1971. El año 2008, se identificó el rol de variantes patogénicas del gen PCDH19 en algunas familias. La enfermedad se presenta con crisis febriles en cluster, DI y rasgos autistas. La mayoría se debe a variantes de novo, pero hay algunos casos heredados por un modo peculiar de transmisión ligada X. OBJETIVO: Comunicar el caso de una paciente con epilepsia portadora de una variante patogénica en el gen PCDH1 9, revisando la historia natural de la enfermedad y la evidencia disponible para su manejo. CASO CLÍNICO: Paciente femenina, con antecedentes de embarazo y período perinatal normal. A los 6 meses, estando febril, presentó crisis focales motoras en cluster que repitieron a los 14, 18, 21 meses y 3 años siempre asociadas a fiebre, presentando incluso estatus epiléptico. Mantiene biterapia con topiramato y ácido valproico, completando 13 años sin crisis. El estudio del gen SCN1A no mostró anomalías y el estudio del gen PCDH19 reveló una variante patogénica en heterocigosis, "de novo". La paciente ha evolucionado con DI y alteraciones conductuales severas que requieren aten ción de salud mental. CONCLUSIONES: Las variantes patogénicas PCDH19 tienen expresión fenotípica variada. El diagnóstico genético debe sospecharse con la clínica. La morbilidad psiquiátrica a largo plazo puede ser incapacitante.

INTRODUCTION: The association of family cases of epilepsy and intellectual disability in women was reported in 1971. In 2008, the role of pathogenic variants of the PCDH19 gene in some families were identified. The disease presents with febrile seizure clusters, intellectual disability, and autistic features. Most cases are due to de novo variants, however, there are some inherited cases, with an atypical way of X-linked transmission. OBJECTIVE: To report the case of a patient with epilepsy carrier of a pathogenic variant of the PCDH19 gene, reviewing the natural history of this condition and the available evidence for its management. CLINICAL CASE: Female patient, with normal history of pregnancy and perinatal period. At 6 months, while febrile, she presented focal motor seizure clusters that repeated at 14, 18, 21 months and 3 years old, always associated with fever, even presenting status epilepticus. She is on therapy with topiramate and valproic acid, achieving 13 seizure-free years. The analysis of the SCN1A gene showed no abnormalities and the study of the PCDH19 gene revealed a de novo heterozygous pathogenic variant. The patient evolved with intellectual disability and severe behavioral disorders that require mental health team support. CONCLUSIONS: PCDH19 pathogenic variants have varied phenotypic expression. The genetic diagnosis should be guided with the clinical features. Long-term psychiatric morbidity can be disabling.

Prevalencia y perfil de susceptibilidad antimicrobiana en bacterias aisladas de úlceras crónicas infectadas en adultos / Prevalence and susceptibility pattern of bacteria isolated from infected chronic wounds in adult patients

Resumen Introducción: Las úlceras crónicas son un problema de salud pública, agravándose por infecciones bacterianas causadas principalmente por agentes resistentes. Objetivo: Estudiar prevalencia y perfil de susceptibilidad en bacterias aisladas de úlceras crónicas en pacientes adultos. Pacientes y Métodos: Pacientes atendidos en la Fundación Instituto Nacional de Heridas entre mayo y julio de 2014, con úlceras crónicas en extremidades inferiores con signos inflamatorios clínicos. Las muestras fueron cultivadas en aerobiosis y anaerobiosis y para la identificación bacteriana se empleó el sistema de galerías API (Biomerieux). La susceptibilidad in vitro se evaluó según el método de Kirby Bauer. Resultados: Se reclutaron 73 pacientes, entre quienes 46 presentaron úlceras infectadas, diagnosticándose 33 úlceras venosas con predominio de infección polimicrobiana y 10 úlceras de pie diabético con predominio de infección monomicrobiana (p ≤ 0,05). Se aislaron 68 cepas de los 46 pacientes con úlcera infectada. Las enterobacterias predominaron en infección monomicrobiana (p ≤ 0,05) y los demás grupos bacterianos fueron levemente más frecuentes en infección polimicrobiana. La especie prevalente fue Staphylococcus aureus (24%) seguida de Pseudomonas aeruginosa (18%). Cincuenta cepas (77%) presentaron resistencia a uno o más antibacterianos. Destacamos resistencia de S. aureus a ciprofloxacina (50%) y cefoxitina (37,5%) identificándose así resistencia a meticilina en la comunidad (SARM-AC), siendo todas sensibles a cotrimoxazol. Las enterobacterias presentaron resistencia a sensibilidad a amikacina (95,5%), P. aeruginosa evidenció resistencia a ciprofloxacina (33,3%) con alta sensibilidad a gentamicina (91,7%) y amikacina (83,3%), mientras Acinetobacter spp presentó resistencia a ciprofloxacina y ceftazidima en 60%, con 100% de sensibilidad a imipenem. Streptococcus β hemolítico presentó 50% de resistencia a clindamicina y penicilina. Conclusión: Estos datos entregan información epidemiológica de infecciones de úlceras crónicas, representando un apoyo al diagnóstico, tratamiento y manejo de esta patología.

Background: Chronic wounds are considered a public health problem that may be complicated by bacterial infections, mainly caused by resistant strains. Aim: To study the bacteria prevalence and antimicrobial susceptibility in samples from adult patients with chronic wounds. Methods: Patients treated at National Institute of Wounds Foundation between May and July 2014, with chronic ulcers in lower extremities with clinical inflammatory signs were recluted. Samples were cultured in aerobic and anaerobic atmosphere and species identification was performed by API (Biomerieux) galleries. The in vitro susceptibility was evaluated according to the Kirby Bauer method. Results: From 73 patients, 46 had infected wounds most of them were venous ulcers (33) with prevalence in polymicrobial infections and 10 with foot-diabetes ulcers with prevalence in monomicrobial infections (p ≤ 0.05). Sixty-eight strains were isolated and Enterobacteriaceae were predominant in monomicrobial infection (p ≤ 0.05) and the other groups were slightly higher in polymicrobial infection. The main species were Staphylococcus aureus (24%) followed by P. aeruginosa (18%). Fifty strains (77%) were resistant or multi-resistance. We emphasize resistance of S. aureus to ciprofloxacin (50%) and cefoxitin (37.5%), thus identifying resistance to methicillin in the community (CA-SAMR), all of which are sensitive to cotrimoxazole. Enterobacteria showed sensitivity to amikacin (95.5%), P. aeruginosa showed resistance to ciprofloxacin (33.3%) with high sensitivity to gentamicin (91.7%) and amikacin (83.3%), while Acinetobacter spp showed resistance to ciprofloxacin and ceftazidime in 60%, with 100% sensitivity to imipenem. 50% Streptococcus β hemolytic showed resistance to clindamycin and penicillin. Conclusion: These data provide epidemiological information on chronic wound infections, representing support for diagnosis, treatment and management of this pathology.

Comportamiento antibacteriano de partículas de cobre frente a microorganismos obtenidos de úlceras crónicas infectadas y su relación con la resistencia a antimicrobianos de uso común / Antibacterial activity of copper salts against microorganisms isolated from chronic infected wounds

Background: The antimicrobial activity of copper (Cu+2) is recognized and used as an antimicrobial agent. Aim: To evaluate the antimicrobial activity of copper against microorganisms obtained from chronic cutaneous wound infections. Material and Methods: Five chemical products that contained copper particles in their composition were tested (zeolite, silica, acetate, nitrate and nanoparticle of copper). The antimicrobial activity against antibiotic resistant strains usually isolated from chronic cutaneous wound infections was determined for two of the products with better performance in copper release. Results: The minimal inhibitory and minimal bactericidal concentrations of copper acetate and nitrate were similar, fluctuating between 400-2,000 µg/ml. Conclusions: The studied copper salts show great potential to be used to control both gram positive and gram negative, antibiotic resistant bacteria isolated from wound infections.

Nuevos fármacos antiepilépticos en epilepsias de la infancia / New antiepileptic drugs for childhood epilepsies

La epilepsia es una enfermedad neurológica muy frecuente que afecta al 0,5 a 1% de todos los niños. La era moderna de los fármacos antiepilépticos (FAEs), que abarca los últimos 150 años, desde el uso del bromuro hasta el presente, ha visto la introducción de diversos fármacos eficaces y seguros que han proporcionado grandes beneficios a pacientes que sufren epilepsia. En Europa y Estados Unidos están aprobados aproximadamente 31 FAEs, 11 de los cuales han sido aprobados por la FDA en los últimos 20 años. El objetivo general que guía el uso de FAEs es alcanzar la libertad de crisis con mínimos efectos adversos. A pesar de la disponibilidad de nuevas opciones, la tasa de fracaso con el primer FAE usado en epilepsia recién diagnosticada mantiene cifras entre 20 a 40%, tanto por falta de eficacia o por efectos adversos intolerables. En esta revisión de nuevos FAEs, veremos que muchos se encuentran disponibles en el mercado hace más de 10 años, sin embargo aún no han sido registrados ni están disponibles para su uso en Chile. Para cada fármaco se presenta su historia y datos relevantes en relación a farmacocinética, dosificación, evidencias de su utilidad así como los principales efectos adversos reconocidos. La facilidad para acceder a nuevos FAEs, requiere que los clínicos consideren cuidadosamente las opciones evaluando todos estos aspectos. Aunque en pacientes pediátricos puede ser particularmente desafiante, hay una mayor urgencia en el control de crisis, dada la evidencia desde los estudios en animales que indican que el control precoz de las crisis mejora el pronóstico futuro. Palabras clave: fármacos antiepilépticos, anticonvulsivantes, epilepsia, tratamiento de la epilepsia, epilepsia en niños y adolescentes

Epilepsy is a common neurological disease that affects 0.5 to 1% of all children. The modern era of antiepileptic drugs (AED), that covers the last 150 years, from the use of the bromide until the present, has seen the introduction of various effective and safe drugs that have provided large benefits to patients that suffer epilepsy. In Europe and the United States there are approximately 31 approved AED, 11 of which have been approved by the FDA in the past 20 years. The general objective that guides the use of AED is to achieve freedom of crisis with minimal adverse effects. Despite the availability of new options, the failure rate with the first AED used in newly diagnosed epilepsy is still between 20 to 40%, either for lack of efficacy or intolerable adverse effects. In this review of new AED, we will see that there are many drugs that have been available for over 10 years, however they are still not registered or available in Chile. We present the history and relevant information for each drug, in regard to pharmacokinetics, dosage, evidence of its usefulness as well as the main recognized adverse effects. The ease of access to new AED, requires that the physician evaluates these aspects carefully. Although pediatric patients can

Biopsychosocial characteristics of patients with neuropathic pain following spinal cord trauma injury. Case reports / Características biopsicossociais associadas a pacientes com dor neuropática por lesão medular traumática. Relato de casos

ABSTRACTBACKGROUND AND OBJECTIVES:Spinal cord injury is a change in spinal canal structures and may induce motor, sensory, autonomic and psychoaffective changes. Trauma injury is the most prevalent. Neuropathic pain is more frequent in people with spinal cord injury and may be disabling. Pain development mechanism is poorly known being its management difficult for both patients and health professionals. This study aimed at identifying biopsychosocial characteristics associated to neuropathic pain in spinal cord trauma injury patients.CASE REPORTS:Sample was made up of 13 patients with spinal cord trauma injury and neuropathic pain, hospitalized for rehabilitation in a health institution. The following data collection tools were used: Douleur Neuropathique em 4 Questions Questionnaire and Brief Pain Inventory, in addition to demographic data. Most patients were male, mean age of 40 years, retired or unemployed. Most frequent cause of spinal cord injury was car accident, followed by firearm and falls. The thoracic segment was more commonly affected, with prevalence of incomplete injuries. Neuropathic pain onset was predominantly within six months after spinal cord injury. Pharmacological treatment was the most cited and considered very effective by 70% of those who use it. Cold and immobility were the most common factors worsening pain; physical activity and leisure were factors improving pain. Mood and general activities were those influenced the most by neuropathic pain.CONCLUSION:Spinal cord trauma injury dramatically changes patients’ lives, generating disastrous consequences for those suffering the injury, their families and for society. In this series, most patients were young males, victims of car accidents and with neuropathic pain negatively impacting mood and general activities.

RESUMOJUSTIFICATIVA E OBJETIVOS:A lesão medular é uma alteração nas estruturas do canal medular, podendo ocasionar dificuldades motoras, sensitivas, autonômicas e psicoafetivas. A lesão traumática possui maior prevalência. A dor neuropática é a mais frequente em pessoas com lesão medular, podendo assumir aspecto incapacitante na vida dessas pessoas. É pouco compreendido o mecanismo de desenvolvimento dessa dor sendo seu tratamento de difícil manuseio para o indivíduo e para os profissionais de saúde. O objetivo deste estudo foi identificar as características biopsicossociais associadas à dor neuropática em pessoas com lesão medular traumática.RELATO DOS CASOS:A amostra foi composta por 13 pacientes com lesão medular traumática e dor neuropática, internados para reabilitação em uma instituição de saúde. Foram utilizados os instrumentos de coleta de dados: Questionário Douleur Neuropathique em 4 Questions, Inventário Breve da Dor, acrescentando os dados demográficos. A maioria dos pacientes era do gênero masculino, idade média de 40 anos, aposentados ou desempregados. A causa predominante da lesão medular foi acidente de trânsito, seguido de arma de fogo e queda. O segmento torácico foi o mais acometido, com prevalência de lesões incompletas. Predominou o início da dor neuropática em até seis meses após a lesão medular. O tratamento farmacológico foi o mais citado e considerado muito efetivo por 70% dos que o utilizam. O frio e a imobilidade prevaleceram como fatores de piora da dor; a atividade física e o lazer como fatores que melhoraram a dor. O humor e a atividade geral foram os mais influenciados pela presença da dor neuropática.CONCLUSÃO:A lesão medular traumática altera drasticamente a vida do paciente acometido, gerando consequências desastrosas para quem sofreu a lesão, para seus familiares e para a sociedade. Nesta série, a maioria foram homens jovens, vítimas de acidentes de trânsito e com dor neuropática que impactava negativamente o humor e as suas atividades gerais.

Efeito do treinamento físico na qualidade de vida, capacidade funcional e fatores de risco cardiovascular nos portadores de doença renal crônica em tratamento conservador / Effect of exercise training n quality of life, functional capacity and cardiovascular risk factors in patients with chronic kidney disease on conservative treatment

A Doença Renal Crônica (DRC) é um importante problema mundial de saúde pública. A DRC apresenta, dentre os principais sintomas, a fadiga, a fraqueza muscular e a baixa tolerância ao exercício, sintomas que contribuem diretamente para o sedentarismo e a baixa mobilidade, com consequente aumento da morbidade e mortalidade. Pacientes com DRC apresentam pobre qualidade de vida, incidência elevada de doenças cardiovasculares, alta prevalência de inflamação crônica e disfunção endotelial com aumento de rigidez arterial, da massa ventricular esquerda e da concentração sérica de dimetilarginina assimétrica (ADMA). Acredita-se que o condicionamento físico desses pacientes possa atenuar fatores de risco cardiovascular e implicar na melhora da qualidade de vida e da capacidade funcional. Vários trabalhos têm avaliado essa premissa em pacientes em diálise, porém poucos estudos a avaliaram em portadores de DRC em tratamento conservador. Avaliar o impacto do treinamento físico em relação à capacidade funcional, qualidade de vida e fatores de risco cardiovascular não tradicionais em portadores de DRC em tratamento conservador. Ensaio clínico, prospectivo e controlado, não randomizado, composto por 16 portadores de DRC, estágios de II a IV, em tratamento conservador, divididos, de acordo com sua disponibilidade e vontade, em grupo controle (GC) e grupo treinamento (GT). Todos os pacientes foram avaliados inicialmente com a realização de teste ergométrico (protocolo de Bruce) em esteira ergométrica para estratificar a capacidade aeróbica por meio do VO2max estimado. Foi realizado Teste de caminhada de 6 minutos para avaliar aptidão física. Foi avaliada pressão arterial central e parâmetros de rigidez arterial com o aparelho Sphygmocor e realizado Ultrassonografia para a mensuração de diâmetros arteriais e de massa cardíaca...

Chronic Kidney Disease (CKD) is a worldwide major public health problem. The CKD has among the main symptoms, fatigue, muscle weakness and poor exercise tolerance, symptoms that directly contribute to physical inactivity and low mobility, with consequent increased morbidity and mortality. CKD patients have poor quality of life, increased incidence of cardiovascular diseases, high prevalence of chronic inflammation and endothelial dysfunction with increased arterial stiffness, left ventricular mass and serum concentration of asymmetric dimethylarginine (ADMA). It is believed that the improvement at physical fitness of these patients may attenuate cardiovascular risk factors and result in improved quality of life and functional capacity. Several studies have evaluated this premise in dialysis patients, but few studies have evaluated in CKD patients on conservative treatment. Evaluate the impact of exercise training at functional capacity, quality of life and non-traditional cardiovascular risk factors in CKD patients on conservative treatment. Clinical trial, prospective, controlled and non-randomized study, comprising 16 patients with CKD stages II to IV, undergoing conservative treatment, divided according to their availability and desire in control group (CG) and training group (GT). All patients were evaluated with the Exercise Test (Bruce protocol) at treadmill to stratify aerobic capacity through VO2max. 6-minute walk test was performed to assess physical fitness. We evaluated central blood pressure and arterial stiffness parameters with the device Sphygmocor and used ultrasound for the measurement of arterial diameters and cardiac mass. Laboratory tests were also collected to establish the full extent of renal inflammation and serum concentration of ADMA...

Maior nível de atividade física associa-se a melhor função cognitiva em renais crônicos em hemodiálise / Greater level of physical activity associated with better cognitive function in hemodialysis in end stage renal disease

INTRODUÇÃO: Pacientes com doença renal crônica (DRC) apresentam menor tolerância ao exercício e baixa capacidade funcional, o que os torna, via de regra, sedentários. Outra alteração importante encontrada na DRC é a disfunção cognitiva. O sedentarismo tem sido associado à disfunção cognitiva na população geral, porém, poucos estudos avaliaram essa associação na DRC. OBJETIVOS: Verificar associação entre o nível de atividade física e a função cognitiva de pacientes com DRC que realizam hemodiálise (HD). MÉTODOS: Foram avaliados 102 pacientes que realizam HD. Os participantes responderam o Questionário Internacional de Atividade Física, que avalia o nível de atividade física e o Mini Exame do Estado Mental, utilizado para o rastreamento cognitivo. Os pacientes foram divididos em três grupos conforme a classificação do nível de atividade física (GI: ativos/GII: irregularmente ativos/GIII: sedentários). Foi aplicada análise de regressão logística adotando-se como variável desfecho a presença de disfunção cognitiva e preservando como variáveis independentes aquelas com probabilidade estatística de diferença entre os grupos inferior a 0,1. Foi considerado estatisticamente significante o valor de p inferior a 0,05. RESULTADOS: Os grupos foram semelhantes quanto à idade, tempo de HD, escolaridade e tabagismo. Apresentaram diferença estatisticamente significante quanto à raça, índice de massa corporal, presença de diabetes mellitus, doença de base e grau de déficit cognitivo. Quanto aos dados laboratoriais, os grupos diferiram quanto à creatinina, glicemia, hemoglobina e hematócrito. Houve associação entre o nível de atividade física e função cognitiva, mesmo ajustando-se para as variáveis de confusão. CONCLUSÃO: O maior nível de atividade física associou-se a melhor função cognitiva em renais crônicos em HD, independentemente das variáveis de confusão avaliadas.

INTRODUCTION: Patients with chronic kidney disease (CKD) have a lower exercise tolerance and poor functional capacity, carry on a sedentary lifestyle. Another important change found in patients with CKD is cognitive dysfunction. Physical inactivity has been associated with cognitive dysfunction in the general population, but few studies have evaluated this association in CKD. OBJECTIVES: To assess the association between physical activity and cognitive function in patients with CKD on hemodialysis (HD). METHODS: We evaluated 102 patients undergoing HD. The participants completed the International Physical Activity Questionnaire, which assesses the level of physical activity and the Mini Mental State Examination, used for cognitive screening. Patients were divided into three groups according to their level of physical activity (GI: active/GII: irregularly active/GIII: sedentary). It was applied logistic regression analysis and adopted as outcome variable the presence of cognitive impairment and preserving as independent variables those with a probability of statistical difference between groups of less than 0.1. It was considered statistically significant when p less than 0.05. RESULTS: The groups were similar in age, duration of HD, and smoking. Statistically significant difference regarding race, body mass index, diabetes mellitus, underlying disease and degree of cognitive impairment. Regarding laboratory data, the groups differed in terms of creatinine, glucose, hemoglobin and hematocrit. There was significant association with better physical activity and cognitive function, even adjusting for confounding variables. CONCLUSION: the highest level of physical activity was associated with better cognitive function in CKD patients undergoing HD.

Enfermedad, muerte y transformación en la vivencia terapéutica / Disease, death and transformation from the therapeutic experience

Este artículo hace referencia a três procesos terapêuticos íntimamente conectados a través de la transferencia y la contra transferencia. El síntoma, la urgência de la muerte frente al câncer terminal y cómo el abordaje terapéutico va cimentando las bases de la elaboración de un complejo en los dos casos clínicos a que se hace alusión, como asismismo en el processo personal de la terapeuta.

This article refers to three therapeutic processes, which are closely connected through transference and counter-transference. It aims to deal with symptom, imminence of death due to terminal cancer and how therapeutic approach consolidates the bases of the preparation of a compound in mentioned clinical cases, as well as in the therapist’s personal process.

Cuidado en sala cuna: impacto sobre la patología respiratoria aguda baja del menor de 2 años / Day care attendance: impact over acute low respiratory pathology in child under 2 years old

Aim: To measure the impact of day care attendance on lower respiratory tract infections in children under 2 years old in 2 urban settings with different degrees of air pollution. Subjects and Methods: a 26 week follow up, during fall and winter of 1991 and 1992, was performed to 98 children (48 attending day care and 50 controls) comming from Santiago, a city affected by severe air pollution and 95 children (46 Attending day care and 49 controls) coming from San felipe and Los Andes (villages with low air pollution). The incidence of lower respiratory infections was recorded by trained personnel and expressed as rates per 100 weeks of follow up. Day care settings in San Felipe and Los Andes were state funded whereas those from Santiago were private. All premises has wooden or plastic floors and smoking was forbidden. During the follow up years, no respiratory epidemic were recorded. Results: The socioeconomic level of children from San Felipe and Los Angeles was better. Children from Santiago were more exposed to tobacco smoke. The highest incidence of lower respiratory infections was found in children attending day care in San Felipe and Los Andes (31.2 episodes/100 weeks of observation), closely followed by control and day care attending children from Santiago (28.7 respectively) and control children from San felipe and Los Andes (18.2). Conclusions: Day care attendance in areas with low air pollution increases the risk of lower respiratory infections. Instead, in highly polluted areas, the infection rates do not increase