Childhood obesity: Pharmacokinetics considerations for drugs used in the Intensive Care Unit. / Obesidad pediátrica: consideraciones farmacocinéticas de los medicamentos utilizados en Terapia Intensiva.

An adequate drug dosage at treatment initiation is particularly relevant for critically ill patients. An inadequate dosage may result in therapeutic failure, potentially severe adverse events, and unnecessary health expenditures. At present, due to the higher incidence of childhood obesity, primary care physicians are more commonly faced with this population, so they need to make appropriate therapeutic decisions. Knowledge of the resulting pharmacokinetic alterations caused by increased body fat is critical. The optimal drug dosage is not completely defined and the correct body descriptor should be used, although there is no consensus on which is the most adequate one. The objective of this update is to gain insight on pharmacokinetic alterations that affect dosage in the critically ill obese pediatric patient and, specifically, those related to the drugs most commonly used in this population during their stay in the pediatric intensive care unit.

La correcta dosificación de un medicamento al inicio de la terapia es de particular relevancia para el paciente críticamente enfermo. Una dosis inadecuada puede ocasionar falla terapéutica, eventos adversos potencialmente graves y gastos innecesarios en salud. Hoy, debido al incremento en la incidencia de obesidad infantil, el médico clínico, cada vez más, se enfrentará a esta población, por lo que es necesaria la adecuada toma de decisiones terapéuticas. El conocimiento de las alteraciones farmacocinéticas resultantes del incremento de grasa corporal es trascendental. La dosis óptima de fármacos no está totalmente definida y debe utilizarse un adecuado descriptor corporal (no existe consenso sobre cuál es el más apropiado). El objetivo de esta actualización es conocer las alteraciones farmacocinéticas que influyen en la dosificación en el paciente pediátrico obeso críticamente enfermo y, en forma particular, las referidas a los fármacos más empleados en esta población durante su estadía en Terapia Intensiva Pediátrica.

An ecotoxicological view on neurotoxicity assessment.

The numbers of potential neurotoxicants in the environment are raising and pose a great risk for humans and the environment. Currently neurotoxicity assessment is mostly performed to predict and prevent harm to human populations. Despite all the efforts invested in the last years in developing novel in vitro or in silico test systems, in vivo tests with rodents are still the only accepted test for neurotoxicity risk assessment in Europe. Despite an increasing number of reports of species showing altered behaviour, neurotoxicity assessment for species in the environment is not required and therefore mostly not performed. Considering the increasing numbers of environmental contaminants with potential neurotoxic potential, eco-neurotoxicity should be also considered in risk assessment. In order to do so novel test systems are needed that can cope with species differences within ecosystems. In the field, online-biomonitoring systems using behavioural information could be used to detect neurotoxic effects and effect-directed analyses could be applied to identify the neurotoxicants causing the effect. Additionally, toxic pressure calculations in combination with mixture modelling could use environmental chemical monitoring data to predict adverse effects and prioritize pollutants for laboratory testing. Cheminformatics based on computational toxicological data from in vitro and in vivo studies could help to identify potential neurotoxicants. An array of in vitro assays covering different modes of action could be applied to screen compounds for neurotoxicity. The selection of in vitro assays could be guided by AOPs relevant for eco-neurotoxicity. In order to be able to perform risk assessment for eco-neurotoxicity, methods need to focus on the most sensitive species in an ecosystem. A test battery using species from different trophic levels might be the best approach. To implement eco-neurotoxicity assessment into European risk assessment, cheminformatics and in vitro screening tests could be used as first approach to identify eco-neurotoxic pollutants. In a second step, a small species test battery could be applied to assess the risks of ecosystems.

[Down Syndrome child in the Intensive care unit]. / El niño con Síndrome de Down en la Unidad de Cuidados Intensivos.

Down syndrome is the most common chromosomal abnormality in newborns, with a high incidence in Chile. This condition presents unique physiological aspects that should be known, which can affect the child during their stay in an Intensive Care Unit, beyond the neonatal period This review is focused on the respiratory, cardiovascular, infectious and neurological disorders. Anesthetic management and postoperative analgesia considerations, weaning from mechanical ventilation, cervical spine instability and prognosis of the critically ill child with Down syndrome are also analyzed. The evaluation of these conditions should be performed when the patient is admitted to the intensive care unit. The purpose of this update is to update the knowledge of the diagnosis and treatment of potential complications of children with Down syndrome during their stay in the unit of critical patient.

El niño con Síndrome de Down en la Unidad de Cuidados Intensivos / Down Syndrome child in the Intensive care unit

El síndrome de Down es la alteración cromosómica más frecuente en los recién nacidos, con una alta incidencia en Chile. Esta condición presenta aspectos fisiológicos únicos, los cuales pueden afectar al niño durante su estadía en una Unidad de Cuidados Intensivos, posterior al período neonatal. En esta revisión abordamos aspectos actuales de la patología respiratoria, cardiovascular, infecciosa y neurológica, así como también consideraciones anestésicas y de analgesia postoperatoria, destete de la ventilación mecánica, inestabilidad columna cervical y pronóstico del niño críticamente enfermo portador de síndrome de Down. La evaluación de todas estas condiciones debe ser realizada cuando el paciente es ingresado a la Unidad de Cuidados Intensivos. El objetivo de la presente actualización es profundizar el conocimiento del diagnóstico y tratamiento de las potenciales complicaciones del niño con síndrome de Down durante su estadía en la unidad de paciente crítico.

Down syndrome is the most common chromosomal abnormality in newborns, with a high incidence in Chile. This condition presents unique physiological aspects that should be known, which can affect the child during their stay in an Intensive Care Unit, beyond the neonatal period This review is focused on the respiratory, cardiovascular, infectious and neurological disorders. Anesthetic management and postoperative analgesia considerations, weaning from mechanical ventilation, cervical spine instability and prognosis of the critically ill child with Down syndrome are also analyzed. The evaluation of these conditions should be performed when the patient is admitted to the intensive care unit. The purpose of this update is to update the knowledge of the diagnosis and treatment of potential complications of children with Down syndrome during their stay in the unit of critical patient.

In vitro modulation of Drimys winteri bark extract and the active compound polygodial on Salmo salar immune genes after exposure to Saprolegnia parasitica.

The rapid development of the aquaculture industry has global concerns with health management and control strategies to prevent and/or treat diseases and increase sustainability standards. Saprolegniosis is a disease caused by Saprolegnia parasitica, and is characterized by promoting an immunosuppression in the host. This study evaluated in vitro the extract and one active compound (polygodial) of Drimys winteri, a Chilean medicinal tree as a potential early immunostimulatory aid in Saprolegniosis control. Atlantic salmon (Salmo salar) head kidney cells (ASK-1) were incubated with both extract and pure polygodial before exposure to S. parasitica mycelium, and the expression of the immune-related genes interleukin 1ß (IL-1ß), interferon α (IFNα), and major histocompatibility complex II (MHCII) was evaluated. Both evidenced immunomodulatory capacities by increasing gene expressions. This immunomodulation related to a mitigatory action counteracting the immunosuppressing effects of S. parasitica. Despite that most immune-related genes were up-regulated, the down-regulation of MHCII, characteristic of S. parasitica infection, was lessened by pre-incubation with the compounds. This study provides the first insight on the potential of D. winteri bark extract as a possible immunomodulatory and defensive strategy against this oomycete infection in fish.

Citotoxicidad de ciclozonarona sobre líneas celulares de fibroblastos y de cáncer de próstata / Cytotoxicity of Cyclozonarone on fibroblasts and prostate cancer cellular lines

INTRODUCCIÓN: El cáncer es una importante causa de mortalidad a nivel mundial, lo que ha motivado la búsqueda de compuestos que ayuden a su remisión, incluyendo compuestos naturales. En este contexto, las sesquiterpén quinonas son evaluadas como posibles sustancias antitumorales por sus propiedades citotóxicas. Una de ellas es Ciclozonarona...

INTRODUCTION: Cancer is a major cause of death in the world, which has motivated the search of compounds that could help to its remission, including natural compound. In this context sesquiterpene quinones are evaluated as possible antitumor substances for its cytotoxic properties, one of them is Ciclozonarone...

Impacto de la violencia doméstica sobre la salud reproductiva y neonatal / Impact of domestic violence on reproductive and neonatal health

Background: Domestic violence can have an important influence on mother and child health. Aim: To assess the consequences of remote and actual, emotional or physical, domestic violence on the reproductive and newborn health in pregnant women. Material and methods: A longitudinal epidemiological observation from an Urban Primary Health Care Center from Valdivia, Chile, in 1998. Two cohorts were studied: Pregnant women that experienced domestic violence (index group) and pregnant women not exposed to domestic violence (control group). Women were followed during pregnancy and at labor. The newborn was also assessed. Results: The index group had a higher relative risk (RR) for impending abortion (RR 1.44, 95 per cent confidence interval (CI): 1.07-1.93), hypertensive syndrome of pregnancy (RR 1.5, 95 per cent CI: 1.18-1.96), intrahepatic cholestasis (RR 1.5, 95 per cent CI: 1.1-1.94). Women that experienced violence during pregnancy had a higher risk of urinary tract infection (RR 2.88, 95 per cent CI: 1.28-6.43), intrauterine growth retardation (RR 3.7, 95 per cent CI: 1.77-7.93) and intrahepatic cholestasis. Newborns from the index group had lower weight, size and gestational age. Conclusions: Domestic violence is associated with hypertension during pregnancy and intrauterine growth retardation. The incorporation of bio-psychological evaluation and monitoring systems could attenuate the consequences of domestic violence

Estudio de toxicidad subcrónica de la DL-4-hidroxi, 4-etil, 4-fenil butiramida (HEPB) en el ratón / Study of the subcronic toxicity of DL-4-hydroxy, 4-ethyl, 4-phenyl butyramide in the mouse

Se administró la HEPB por vía oral a ratones (15 machos y 15 hembras) a dosis de 0, 100, 150, 230 y 350 mg/kg peso durante 13 semanas. Cincuenta por ciento de los animales tratados con la dosis más alta (350 mg/kg) murieron. Sin embargo, a las dosis inferiores no se observaron efectos sobre el peso corporal, valores hematológicos, química sanguínea, composición de la orina y peso de los órganos. Se concluye que la administración subcrónica de la HEPB hasta dosis de 230 mg/kg, no produce efectos tóxicos en esta especie. Esta dosis representa una cantidad considerable en relación a la probable dosis a utilizarse en humanos

Anemia megalobástica Asociada a Diarrea crónica.Estudio prospectivo y multicéntrico en Lima / Megaloblástic anemia associated to chronic diarrhea. Prospective and multicentric study in Lima

A partir de 1986 hemos observado un incremento de Anemia Megaloblástica (AM) asociada a diarrea crónica, en 60 por ciento no se encontró ninguna relación causal. En los últimos 3 años hemos utilizado un protocolo multicéntrico prospectivo en Lima (Perú), se incluyeron adultos con AM confirmada por aspirado de médula ósea, excluyendo: ancianos, gestantes, alcohólicos, portadores de neoplasias, etc. Los pacientes fueron 45 con promedio de edad de 37.5 años. Se encontraron dosajes disminuídos de B12 + ácido fólico: 64 por ciento, B12: 20 por ciento, y ácido fólico:16 por ciento. Las biopsias gástricas demostraron atrofia: 33 por ciento (fondo), 7,6 por ciento (cuerpo) y 12 por ciento(antro). El pH gástrico menor o igual a 4.5 en 50 por ciento. El cultivo microbiológico del jugo duodenal fué positivo en 35.2 por ciento 96/17), la mayoría coliformes gram negativos. Presentaron diversas alteraciones estructurales 5/8 (62.5 por ciento) biopsias duodenales, 5/6 (83 por ciento) biopsias yeyunales y 4/4 (100 por ciento) biopsias ileales. Los estudios parasitológicos excluyeron diphillobothrium pacificum. Estos hallazgos nos llevan a sugerir que un significativo número de pacientes con AM y diarrea crónica (con o sin síndrome espruiforme) en Lima, son consecuencia del sobrecrecimiento bacteriano intestinal, lo que los configuraría como casos de Esprue Tropical

[Megaloblastic anemia associated with chronic diarrhea. A prospective and multicenter study in Lima]. / Anemia megaloblástica asociada a diarrea crónica. Estudio prospectivo y multicéntrico en Lima.

Since 1986 we have been observing an increased number of patients with megaloblastic anaemia (MA) associated to chronic diarrhea. In 60% of the cases we could not identify any etiologic factor. In the last three years a prospective study in Lima (Peru) has been carried on aimed to investigate this aspect; patients with diseases recognized to be associated to MA were excluded. 45 patients were included age average 37.5 years, all of them have a confirmed diagnosis by bone marrow; 64% with low serum B12 and folic acid, 20% with low serum B12, and 16% with low serum folic acid. Gastric biopsies did not show atrophy in 67%; intragastric pH was lower than 4 in 50% duodenal content culture was positive in 35% (6/17) to aerobic gram negative agents; 62% (5/8) of duodenal biopsies, 83% (5/6) of jejunal biopsies, 4/4 (100%) of ileal biopsies, showed diverse structural changes; 100% did not show Diphyllobothrium pacificum. All these findings make us suggest that a significative number of patients with MA and chronic diarrhea in Lima are related to small bowel bacterial overgrowth. These bacteria can "sequestrate" or consume folates and cobalamines besides the direct damage they can cause to intestinal morphology. Future studies are needed to confirm our proposal and define if these cases belong to a variety of tropical sprue.

Evaluation of the toxic and teratogenic potential of the anticonvulsant drug 4-hydroxy, 4-ethyl, 4-phenylbutyramide in mice.

The toxicity profiles of the phenyl alcohol amides: 4-hydroxy, 4-ethyl, 4-phenylbutyramide (HEPB) and two lower homologous: 3-hydroxy, 3-ethyl, 3-phenylpropionamide (HEPP) and 2-hydroxy, 2-ethyl, 2-phenylacetamide (HEPA) were studied in mice. TD50 value was determined by oral administration and LD50 by oral and intraperitoneal routes. The results indicate that HEPP is less toxic than the others, both of which had very similar toxicity. Furthermore, the teratogenic potential of HEPB was investigated in mice after oral administration. The compound was administered on days 6-15 of gestation at doses of 0, 5, 25, 50 or 100 mg/kg of weight. On day 17 of pregnancy the mice were sacrificed and the pups examined. An increase of body weight in both mothers and fetuses was observed at 25 and 50 mg/kg and a decrease was found in mothers receiving 100 mg/kg, as a sign of maternal toxicity. Considering the litter data, embryotoxicity and fetotoxicity were only shown at the highest dose. However, the HEPB treatment did not result in malformations of live fetuses or resorptions when the implantations were considered as the individual entity.

Colecistectomía por laparoscopía: experiencia inicial en el Hospital del Cobre / Laparoscopic cholecystectomy: an experience at Hospital del Cobre

Se revisa todas las colecistectomías realizadas en nuestro Servicio, desde el 29 de abril al 29 de mayo de 1991 y que corresponden a 50 pacientes. De éstas 36 fueron realizadas por laparoscopia, lo que representa el 72%. Se analiza la casuística por edad, sexo, duración de la operación, complicaciones, días de hospitalización, días de licencia médica. Se concluye que el método es reproducible por cirujanos generales con experiencia en cirugía biliar, que reciban entrenamiento y que cuenten con el equipamiento adecuado. Que la colecistectomía por laparoscopia ofrece ventajas reales como son la disminución del dolor postoperatorio, disminuye los días de hospitalización y se acortan las licencias postoperatorias. La morbilidad se puede reducir haciendo una adecuada selección inicial de los pacientes

[Teratogenic action of alpha-asarone in the mouse]. / Action tératogène de l'alpha-asarone chez la souris.

The embryotoxicity and teratogenicity of alpha-asarone were investigated in mice. The drug was dissolved in corn oil, and administered daily, by gavage, on days 6 to 15 of gestation, at 0 (controls), 5, 15, 30 and 60 mg/kg. Fetuses were removed on day 18 by caesarean section and examined using routine teratological methods. A significant maternal toxicity was observed in dams given 60 mg/kg, as indicated by a reduced weight gain. An embryolethality was observed in 15, 30 and 60 mg/kg treated groups. In addition, the highest dose induced fetal malformations, mainly represented by hydrocephaly, extra-ribs, clubfeet and cleft lips.

Complicaciones tardías de la fractura de cráneo con lesión meníngea: presentación de tres casos clínicos / Late complications of craneal fracture with meningeal injury: presentation of 3 clinical cases

Se describen tres casos de complicación tardía de una fractura de cráneo con compromiso meníngeo: Un encefalocele orbitario con exoftalmo unilateral intermitente, una fractura crecedora de un adulto y un hundimiento craneano con rotura dural, 39, 29 y 16 años, respectivamente, después de un tratamiento craneoencefálico. Se confrontan estos casos con la literatura. Se describe el tratamiento neuroquirúrgico. Se comenta lo infrecuente de estas complicaciones tardías del traumatismo craneoencefálico

Use of nebulized bronchodilators in infants under 1 year of age: analysis of four forms of therapy.

The main purpose of this study was to evaluate four different forms of treatment in young infants admitted for acute wheezing (AW). Seventy-nine infants less than one year of age were randomly assigned to one of five groups. Group 1 received nebulized fenoterol plus ipratropium bromide, group 2 fenoterol, group 3 fenoterol plus steroids, and group 4 aminophylline, IV, plus steroids and oral fenoterol; the control group, or group 5, received nebulized normal saline solution. Clinical evaluation was done by means of a scoring system. The effectiveness of treatments was estimated by a score decrease in the first 24 hours, by the percentage of patients whose scores did not decrease during the same period, and by the number of days in the hospital. All infants had significantly decreased scores, except those in the control group; the aminophylline group included a greater percentage of patients who did not abate their scores, and they stayed in the hospital for more days than those in the other groups. The fenoterol group had the shortest hospital stay. All four treatments produced objective clinical improvement in bronchial obstruction. However, the nebulized bronchodilator treatments were more effective than aminophylline IV in decreasing scores on the first day, and they resulted in shorter hospitalization.

Effects of nebulized fenoterol, associated with ipratropium or steroids, on the heart rate of infants under one year of age with acute wheezing.

The main objective of this study was to evaluate the effect of fenoterol alone or associated with ipratropium bromide or steroid on the heart rate in young children. Ninety-four infants less than 1 year of age were randomly allocated to receive nebulized fenoterol alone, fenoterol plus ipratropium bromide, fenoterol plus corticosteroids, or normal saline solution. An increase in heart rate was observed in all four groups. The increases were statistically significant (P less than 0.001) in all three treatment groups, and no difference between them was observed (F = 0.65, NS). However, the heart rate remained within clinically acceptance limits. We conclude that nebulized fenoterol alone or combined with ipratropium or steroids can be safely used in the treatment of wheezy infants.