Variantes del gen ABCB1 como factores de riesgo y factores moduladores de la edad de inicio en pacientes mexicanos con enfermedad desmielinizante / ABCB1 gene variants as risk factors and modulators of age of onset of demyelinating disease in Mexican patients

Introducción: Las variantes C1236T, G2677T/A y C3435T del gen ABCB1 alteran la función de la glicoproteína P y el transporte de sustancias endógenas y exógenas en la barrera hematoencefálica; además, actúan como factores de susceptibilidad para algunas enfermedades neurodegenerativas.El objetivo del estudio fue determinar la asociación de polimorfismos ABCB1 (C1236T, G2677T/A y C3435T), sus haplotipos y sus combinaciones de genotipos con la enfermedad desmielinizante.MétodoSe genotipificó a 199 pacientes con enfermedad desmielinizante y a 200 controles mestizos mexicanos mediante PCR-RFLP y secuenciación Sanger para comparar las frecuencias de alelos, genotipos, haplotipos y combinaciones de genotipos entre pacientes y controles. El análisis estadístico se realizó con regresión logística y χ2 de Pearson al 95% de confianza; se calculó la OR y se evaluó la asociación con enfermedad desmielinizante.ResultadosLos haplotipos TTT y CGC fueron los más frecuentes en pacientes y controles. El alelo G2677 (OR = 1,79; IC 95%: 1,12-2,86; p = 0,015) muestra asociación con enfermedad desmielinizante, así como los genotipos GG2677 (OR = 2,72; IC 95% = 1,11-6,68; p = 0,025) y CC3435 (OR = 1,82; IC 95%: 1,15-2,90; p = 0,010) y su combinación GG2677/CC3435 (OR = 2,02; IC 95%: 1,17-3,48; p = 0,010) y el haplotipo CAT (OR = 0,21; IC 95%: 0,05-0,66; p = 0,001).Los portadores TTTTTT presentaron la edad de inicio más temprana (23,0 ± 7,7 vs. 31,6 ± 10,7; p = 0,0001).ConclusionesLa combinación de genotipos GG2677/CC3435 está asociada al desarrollo de enfermedad desmielinizante en esta muestra, principalmente en el sexo masculino, en el cual puede darse acumulación tóxica de sustratos de glicoproteína P.En este estudio, la edad de inicio de la enfermedad desmielinizante podría ser modulada diferencialmente entre sexos por el alelo G2677 del gen ABCB1. (AU)

Introduction: The C1236T, G2677T/A, and C3435T variants of the ABCB1 gene alter the functioning of P-glycoprotein and the transport of endogenous and exogenous substances across the blood-brain barrier, and act as risk factors for some neurodegenerative diseases.This study aimed to determine the association between demyelinating disease and the C1236T, G2677T/A, and C3435T variants of ABCB1 and its haplotypes and combinations of genotypes.MethodsPolymerase chain reaction with restriction fragment length polymorphism analysis (PCR-RFLP) and Sanger sequencing were used to genotype 199 patients with demyelinating disease and 200 controls, all Mexicans of mixed race; frequencies of alleles, genotypes, haplotypes, and genotype combinations were compared between patients and controls. We conducted a logistic regression analysis and calculated chi-square values and 95% confidence intervals (CI); odds ratios (OR) were calculated to evaluate the association with demyelinating disease.ResultsThe TTT and CGC haplotypes were most frequent in both patients and controls. The G2677 allele was associated with demyelinating disease (OR: 1.79; 95% CI: 1.12-2.86; P = .015), as were the genotypes GG2677 (OR: 2.72; 95% CI: 1.11-6.68; P = .025) and CC3435 (OR: 1.82; 95% CI: 1.15-2.90; P = .010), the combination GG2677/CC3435 (OR: 2.02; 95% CI, 1.17-3.48; P = .010), and the CAT haplotype (OR: 0.21; 95% CI: 0.05-0.66; P = .001).TTTTTT carriers presented the earliest age of onset (23.0 ± 7.7 years, vs. 31.6 ± 10.7; P = .0001).ConclusionsThe GG2677/CC3435 genotype combination is associated with demyelinating disease in this sample, particularly among men, who may present toxic accumulation of P-glycoprotein substrates.In our study, the G2677 allele of ABCB1 may differentially modulate age of onset of demyelinating disease in men and women. (AU)

ABCB1 gene variants as risk factors and modulators of age of onset of demyelinating disease in Mexican patients.

INTRODUCTION: The C1236T, G2677T/A, and C3435T variants of the ABCB1 gene alter the functioning of P-glycoprotein and the transport of endogenous and exogenous substances across the blood-brain barrier, and act as risk factors for some neurodegenerative diseases. This study aimed to determine the association between demyelinating disease and the C1236T, G2677T/A, and C3435T variants of ABCB1 and its haplotypes and combinations of genotypes. METHODS: Polymerase chain reaction with restriction fragment length polymorphism analysis (PCR-RFLP) and Sanger sequencing were used to genotype 199 patients with demyelinating disease and 200 controls, all Mexicans of mixed race; frequencies of alleles, genotypes, haplotypes, and genotype combinations were compared between patients and controls. We conducted a logistic regression analysis and calculated chi-square values and 95% confidence intervals (CI); odds ratios (OR) were calculated to evaluate the association with demyelinating disease. RESULTS: The TTT and CGC haplotypes were most frequent in both patients and controls. The G2677 allele was associated with demyelinating disease (OR: 1.79; 95% CI, 1.12-2.86; P =  .015), as were the genotypes GG2677 (OR: 2.72; 95% CI, 1.11-6.68; P =  .025) and CC3435 (OR: 1.82; 95% CI, 1.15-2.90; P =  .010), the combination GG2677/CC3435 (OR: 2.02; 95% CI, 1.17-3.48; P =  .010), and the CAT haplotype (OR: 0.21; 95% CI, 0.05-0.66; P =  .001). TTTTTT carriers presented the earliest age of onset (23.0 ±â€¯7.7 years, vs 31.6 ±â€¯10.7; P =  .0001). CONCLUSIONS: The GG2677/CC3435 genotype combination is associated with demyelinating disease in this sample, particularly among men, who may present toxic accumulation of P-glycoprotein substrates. In our study, the G2677 allele of ABCB1 may differentially modulate age of onset of demyelinating disease in men and women.

Establishing the tolerability to broiler chickens and laying hens of nonanoic acid at practical levels of use as a feed flavouring.

1. The following experiments were conducted to evaluate the effects of nonanoic acid (NA) in broilers and laying hens, at practical levels as a flavouring in complete feed.2. In the first experiment, 1100, one-day-old Ross 308 chicks, half male and female, were randomly assigned to 50 floor pens containing 22 chicks each. Chicks were fed one of five treatment diets containing either 0 (control), 100, 300, 500 or 1,000 mg NA/kg complete feed for 42 days.3. The NA treatment had no effect on ADFI, but there was a linear relationship with ADG and FCR. No differences were observed in blood parameters or tissue pathology among treatment groups.4. In a second study, 150 Hyline hens aged 24 weeks old were randomly assigned to 50 pens containing three birds each. Laying hens were fed one of five treatment diets containing 0 (control), 100, 300, 500 or 1,000 mg NA/kg complete feed for 56 days.5. Treatment with NA has no effect on live weight, ADFI or egg production in laying hens, and there were no observed changes in tissue pathology.6. The results supported the toleration of NA in broilers or layers at dietary levels of up to 1,000 mg/kg.

ABCB1 gene variants as risk factors and modulators of age of onset of demyelinating disease in Mexican patients. / Variantes del gen ABCB1 como factores de riesgo y factores moduladores de la edad de inicio en pacientes mexicanos con enfermedad desmielinizante.

INTRODUCTION: The C1236T, G2677T/A, and C3435T variants of the ABCB1 gene alter the functioning of P-glycoprotein and the transport of endogenous and exogenous substances across the blood-brain barrier, and act as risk factors for some neurodegenerative diseases. This study aimed to determine the association between demyelinating disease and the C1236T, G2677T/A, and C3435T variants of ABCB1 and its haplotypes and combinations of genotypes. METHODS: Polymerase chain reaction with restriction fragment length polymorphism analysis (PCR-RFLP) and Sanger sequencing were used to genotype 199 patients with demyelinating disease and 200 controls, all Mexicans of mixed race; frequencies of alleles, genotypes, haplotypes, and genotype combinations were compared between patients and controls. We conducted a logistic regression analysis and calculated chi-square values and 95% confidence intervals (CI); odds ratios (OR) were calculated to evaluate the association with demyelinating disease. RESULTS: The TTT and CGC haplotypes were most frequent in both patients and controls. The G2677 allele was associated with demyelinating disease (OR: 1.79; 95% CI: 1.12-2.86; P=.015), as were the genotypes GG2677 (OR: 2.72; 95% CI: 1.11-6.68; P=.025) and CC3435 (OR: 1.82; 95% CI: 1.15-2.90; P=.010), the combination GG2677/CC3435 (OR: 2.02; 95% CI, 1.17-3.48; P=.010), and the CAT haplotype (OR: 0.21; 95% CI: 0.05-0.66; P=.001). TTTTTT carriers presented the earliest age of onset (23.0±7.7 years, vs. 31.6±10.7; P=.0001). CONCLUSIONS: The GG2677/CC3435 genotype combination is associated with demyelinating disease in this sample, particularly among men, who may present toxic accumulation of P-glycoprotein substrates. In our study, the G2677 allele of ABCB1 may differentially modulate age of onset of demyelinating disease in men and women.

[Nutritional support response in critically ill patients; differences between medical and surgical patients]. / Respuesta al soporte nutricional de una población de pacientes críticos; diferencias entre pacientes médicos y quirúrgicos.

OBJECTIVE: To assess the nutritional response of a group of critically ill patients, as well as the differences in the response to nutritional support between medical and surgical patients. METHODS: One-year long retrospective study including critically ill patients on artificial nutrition for 7 days. Throughout the first week, three nutritional biochemical controls were done that included albumin, prealbumin, transferrin, cholesterol, and electrolytes. Other data gathered were: nutritional risk index, age, gender, weight, height, APACHE, delay of onset of nutritional support, access route, predicted and real caloric intake, medical or surgical patient, hospital stay, duration of the central venous catheter, urinary tube, and/or mechanical ventilation, incidence and density of incidence of nosocomial infections. RESULTS: Sixty-three patients were studied, 30 (47%) medical and 33 (53%) surgical/trauma patients, with a usage of EN higher among medical patients (16/30, 53% vs. 5/33, 15%), PN higher among surgical patients (25/33, 76%), and mixed nutrition similar in both groups (5 medical and 3 surgical patients) (p = 0.001). There were no differences between medical and surgical patients regarding: both predicted and real caloric and nitrogenous intake, APACHE, delay of onset of nutrition, phosphorus, magnesium or glucose levels, mortality and incidence of nosocomial infections. There were no differences either in hospital stay or use of mechanical ventilation, although these tended to be lower in surgical patients. The baseline biochemical parameters did not show differences between both groups, although they were worse among surgical patients. These patients presented during the study period steady albumin levels with improvement in the remaining parameters, whereas medical patients showed a decrease in albumin and transferrin levels, steady prealbumin levels, and slightly improvement in cholesterol levels. CONCLUSIONS: We have observed higher usage of PN among surgical patients, which showed worse baseline nutritional biochemical parameters and responded better to nutritional support and having a trend towards shorter hospital stay and lower mechanical ventilation use than medical patients. We have not observed differences regarding the mortality or nosocomial infection.

Respuesta al soporte nutricional de una población de pacientes críticos; diferencias entre pacientes médicos y quirúrgicos / Nutritional support response in critically ill patients; differences between medical and surgical patients

Objetivo: Evaluación de la respuesta nutricional de un grupo de pacientes críticos, así como el análisis de las diferencias en la respuesta al soporte nutricional, entre pacientes médicos y quirúrgicos. Métodos: Estudio retrospectivo durante un año, incluyendo los pacientes críticos con nutrición artificial durante 7 días. Se realizaron tres controles bioquímicos nutricionales a lo largo de la primera semana, que incluían albúmina, prealbúmina, transferrina, colesterol y electrolitos. Se recogieron, además: índice de riesgo nutricional, edad, sexo, peso, talla, APACHE, retraso del inicio del soporte nutricional, vía de acceso, aporte calórico teórico y real, enfermo médico o quirúrgico, estancia, duración de catéter venoso central, sonda urinaria y/o ventilación mecánica, incidencia y densidad de incidencia de infecciones nosocomiales. Resultados: 63 pacientes estudiados, 30 médicos (47%) y 33 quirúrgicos/traumáticos (53%) siendo la utilización de NE superior en médicos (16/30, 53% vs 5/33, 15%), la de NP en quirúrgicos (25/33, 76%) y la mixta similar en ambos (5 médicos y 3 quirúrgicos) (p = 0,001). No hubo diferencias entre pacientes médicos y quirúrgicos en: aporte calórico y nitrogenado teóricos ni reales, APACHE, retraso en inicio de nutrición, valores de fósforo, magnesio y glucosa, mortalidad e incidencia de infecciones nosocomiales. Tampoco en días de estancia y ventilación mecánica, aunque tendieron a ser menores en pacientes quirúrgicos. Los parámetros bioquímicos iniciales de ambos grupos mostraron diferencias, siendo peores en los enfermos quirúrgicos. Estos presentaron, en el periodo de estudio, un mantenimiento de la albúmina y mejoras del resto de los parámetros, mientras que los médicos mostraron una caída de la albúmina y transferrina, un mantenimiento de la prealbúmina y discreta mejoría del colesterol. Conclusiones: Hemos observado un mayor uso de la NP en pacientes quirúrgicos, que presentan peores valores bioquímicos nutricionales iniciales, que responden mejor al soporte nutricional y que presentan una tendencia a una menor estancia y una menor duración de ventilación mecánica frente a los pacientes médicos. No hemos observado diferencias en mortalidad ni en infección nosocomial (AU)

Objective: To assess the nutritional response of a group of critically ill patients, as well as the differences in the response to nutritional support between medical and surgical patients. Methods: One-year long retrospective study including critically ill patients on artificial nutrition for 7 days. Throughout the first week, three nutritional biochemical controls were done that included albumin, prealbumin, transferrin, cholesterol, and electrolytes. Other data gathered were: nutritional risk index, age, gender, weight, height, APACHE, delay of onset of nutritional support, access route, predicted and real caloric intake, medical or surgical patient, hospital stay, duration of the central venous catheter, urinary tube, and/or mechanical ventilation, incidence and density of incidence of nosocomial infections. Results: Sixty-three patients were studied, 30 (47%) medical and 33 (53%) surgical/trauma patients, with a usage of EN higher among medical patients (16/30, 53% vs. 5/33, 15%), PN higher among surgical patients (25/33, 76%), and mixed nutrition similar in both groups (5 medical and 3 surgical patients) (p = 0.001). There were no differences between medical and surgical patients regarding: both predicted and real caloric and nitrogenous intake, APACHE, delay of onset of nutrition, phosphorus, magnesium or glucose levels, mortality and incidence of nosocomial infections. There were no differences either in hospital stay or use of mechanical ventilation, although these tended to be lower in surgical patients. The baseline biochemical parameters did not show differences between both groups, although they were worse among surgical patients. These patients presented during the study period steady albumin levels with improvement in the remaining parameters, whereas medical patients showed a decrease in albumin and transferrin levels, steady prealbumin levels, and slightly improvement in cholesterol levels. Conclusions: We have observed higher usage of PN among surgical patients, which showed worse baseline nutritional biochemical parameters and responded better to nutritional support and having a trend towards shorter hospital stay and lower mechanical ventilation use than medical patients. We have not observed differences regarding the mortality or nosocomial infection (AU)

Resultados del soporte nutricional en una UCI polivalente / Nutritional support outcomes in critical care

Objetivos: Revisar el efecto de nuestras practicas habituales de soporte nutricional en pacientes críticos y establecer nuevas hipótesis de trabajo. Métodos: Estudio retrospectivo observacional sobre pacientes críticos sometidos a nutrición artificial en el período de un año. Se describe el protocolo de soporte nutricional y se estudian las siguientes variables: APACHE II, retraso en el inicio del soporte nutricional, la vía de administración, el aporte calórico durante la primera semana de soporte nutricional, tipo de paciente, estancia en la unidad, incidencia de infección nosocomial, presencia de complicaciones gastrointestinales y mortalidad. Se estudian los resultados obtenidos y las posibles relaciones entre el tiempo de inicio, la vía de administración y el aporte calórico con los resultados: mortalidad, infección nosocomial, duración de la ventilación mecánica y estancia en la Unidad. Resultados: 102 pacientes que recibieron soporte nutricional fueron seleccionados para el estudio. Estos pacientes mostraron una mayor gravedad, mortalidad y complicaciones infecciosas que los pacientes críticos no sometidos a soporte nutricional. La nutrición enteral fue utilizada en el 41% de los casos, la parenteral en el 40% y la nutrición combinada en el 19%. El soporte nutricional se inició a los 3,1 ± 1,9 días de media, existiendo diferencias entre los pacientes que sobrevivieron y los que no (2,82 ± 1.65 vs 3,74 ± 2,33 días). Los pacientes recibieron el 58 ± 28% de sus requerimientos durante la primera semana de soporte nutricional y no se encontró relación del aporte calórico con la mortalidad, aunque sí con la incidencia de infección nosocomial. Hubo diferencias entre la vía de administración y los siguientes datos: tipo de paciente, aporte calórico, la estancia en UCI y la duración de la ventilación mecánica. Conclusiones: El conjunto de pacientes sometido a soporte nutricional, son pacientes más graves y con peores resultados que los pacientes sin indicación de soporte nutricional. En nuestro estudio el inicio precoz del soporte nutricional, se asoció con una menor mortalidad, aunque no con una menor incidencia de complicaciones infecciosas. El aporte calórico fue bajo, especialmente en pacientes con nutrición enteral, aunque no se relacionó con la mortalidad. Obtuvimos unos mejores resultados clínicos con nutrición parenteral que con la enteral o la parenteral suplementaria. La nueva hipótesis que planteamos es si un aporte calórico moderado y precoz podría asociarse a mejores resultados clínicos, independientemente de la ruta de administración del soporte nutricional (AU)

Background & aims: To revise the effect of our nutritional support practices on outcomes from critical care patients and propose new study hypothesis. Methods: Retrospective observational study was conducted in all critically ill patients who had been prescribed nutritional support, through a year time, in an Intensive Care Unit. The nutritional support practices are described. Severity of illness (Simplified Acute Physiology Score II), timing and route of nutritional support, prescribed and delivered daily caloric intake for a maximum of 7 days, medical or surgical patient, length of stay in ICU, incidence rate and incidence density of nosocomial infections, and presence of gastrointestinal complications were recorded. Relationships between timing and route of nutritional support and percentage of received/ prescribed calories with mortality, nosocomial infections, days of mechanical ventilation and length of stay in the Intensive Care Unit were studied. Results: 102 patients of our intensive care patients received nutritional support and were selected for the study. EN was used in 42 patients (41%), 41 (40%) received TPN and 19 patients (19%) received mixed nutrition. Timing of nutritional support showed a mean of 3.1 ± 1.9 days and was statistically different between patients who survived or died (2.82 ± 1.65 vs. 3.74 ± 2.33 days). Patients received 58 ± 28% of their requirements but this data did not show any difference with mortality and morbidity. There was a statistical difference between the route of nutrition and the following data: type of patient, caloric intake in the study period, length of stay in ICU and days of mechanical ventilation. Conclusions: Our study demonstrates that nutritional support patients are more severely ill than nonnutritional support patients. Timing of nutritional support was shorter in survivors. Our study confirms a low caloric input in the critically ill patient during the first week of illness, especially in the enteral nutrition group. However this finding was not associated with mortality or morbidity. Parenteral route did show better clinical outcomes than enteral or mixed nutrition. Our findings suggest that a moderate and early caloric intake could obtain better outcomes, independently of the route of nutritional support (AU)

[Nutritional support outcomes in critical care]. / Resultados del soporte nutricional en una UCI polivalente.

BACKGROUND & AIMS: To revise the effect of our nutritional support practices on outcomes from critical care patients and propose new study hypothesis. METHODS: Retrospective observational study was conducted in all critically ill patients who had been prescribed nutritional support, through a year time, in an Intensive Care Unit. The nutritional support practices are described. Severity of illness (Simplified Acute Physiology Score II), timing and route of nutritional support, prescribed and delivered daily caloric intake for a maximum of 7 days, medical or surgical patient, length of stay in ICU, incidence rate and incidence density of nosocomial infections, and presence of gastrointestinal complications were recorded. Relationships between timing and route of nutritional support and percentage of received/ prescribed calories with mortality, nosocomial infections, days of mechanical ventilation and length of stay in the Intensive Care Unit were studied. RESULTS: 102 patients of our intensive care patients received nutritional support and were selected for the study. EN was used in 42 patients (41%), 41 (40%) received TPN and 19 patients (19%) received mixed nutrition. Timing of nutritional support showed a mean of 3.1 ± 1.9 days and was statistically different between patients who survived or died (2.82 ± 1.65 vs. 3.74 ± 2.33 days). Patients received 58 ± 28% of their requirements but this data did not show any difference with mortality and morbidity. There was a statistical difference between the route of nutrition and the following data: type of patient, caloric intake in the study period, length of stay in ICU and days of mechanical ventilation. CONCLUSIONS: Our study demonstrates that nutritional support patients are more severely ill than nonnutritional support patients. Timing of nutritional support was shorter in survivors. Our study confirms a low caloric input in the critically ill patient during the first week of illness, especially in the enteral nutrition group. However this finding was not associated with mortality or morbidity. Parenteral route did show better clinical outcomes than enteral or mixed nutrition. Our findings suggest that a moderate and early caloric intake could obtain better outcomes, independently of the route of nutritional support.

Experiences in setting up the first centralized radiopharmacy in Spain.

The centralized radiopharmacy set up in Spain by the Cetir Medical Group allows optimal use of radiopharmaceuticals and complies with laws (Directive 89/343/EEC and Royal Decree 479/1993/Spain) governing their use. More than 220,000 individual patient doses have been supplied since the unit was established in November 1995. In this paper, we describe the infrastructure of the centralized radiopharmacy, including the operations and procedures involved, and how we believe we have achieved our original objectives.