[Reevaluation of the time course of the effect of propofol described with the Schnider pharmacokinetic model]. / Reevaluación del comportamiento del curso temporal del efecto de propofol descrito por el modelo farmacocinético de Schnider.

BACKGROUND: The first order plasma-effect-site equilibration rate constant (k(e0)) links the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. This constant, calculated for each specific PK drug model, allowed us to predict the course of the effect in a target controlled infusion (TCI). The PK-PD model of propofol, published by Schnider et al., calculated a k(e0) value of 0.456min(-1) and a corresponding time to peak effect (t peak) of 1.6min. The aim of this study was to reevaluate the k(e0) value for the predicted Schnider model of propofol, with data from a complete effect curve obtained by monitoring the bispectral index (BIS). METHODS: The study included 35 healthy adult patients (18-90 years) scheduled for elective surgery with standard monitoring and using the BIS XP(®) (Aspect), and who received a propofol infusion to reach a plasma target of 12 µg/ml in 4min. The infusion was then stopped, obtaining a complete effect curve when the patient woke up. The Anestfusor™ (University of Chile) software was used to control the infusion pumps, calculate the plasma concentration plotted by Schnider PK model, and to store the BIS data every second. Loss (LOC) and recovery (ROC) of consciousness was assessed and recorded. Using a traditional parametric method using the "k(e0) Objective function" of the PK-PD tools for Excel, the individual and population k(e0) was calculated. Predictive Smith tests (Pk) and Student t test were used for statistical analysis. A P<.05 indicated significance. RESULTS: The evaluation included 21 male and 14 female patients (18 to 90 years). We obtained 1,001 (±182) EEG data and the corresponding calculated plasma concentration for each case. The population k(e0) obtained was 0.144min(-1) (SD±0.048), very different from the original model (P<.001). This value corresponds with a t peak of 2.45min. The predictive performance (Pk) for the new model was 0.9 (SD±0.03), but only 0.78 (SD±0.06) for the original (P<.001). With a baseline BIS of 95.8 (SD±2.34), the BIS at LOC was 77.48 (SD±9.6) and 74.65(SD±6.3) at ROC (P=.027). The calculated Ce in the original model at LOC and ROC were 5.9 (SD±1.35)/1.08 µg/ml (SD±0.32) (P<.001), respectively, and 2.3 (SD±0.63)/2.0 µg/ml (SD±0.65) (NS) for the new model. The values between LOC/ROC were significantly different between the 2 models (P<.001). No differences in k(e0) value were found between males and females, but in the new model the k(e0) was affected by age as a covariable (0.26-[age×0.0022]) (P<.05). CONCLUSIONS: The dynamic relationship between propofol plasma concentrations predicted by Schnider's pharmacokinetic model and its hypnotic effect measured with BIS was better characterized with a smaller k(e0) value (slower t½k(e0)) than that present in the original model, with an age effect also not described before.

The effect of urban landfill leachate characteristics on the coexistence of anammox bacteria and heterotrophic denitrifiers.

Heterotrophic denitrification coexists with the anammox process contributing to N removal owing to the biodegradable organic matter supply from urban landfill leachate and the decay of microorganisms. Both biomasses consumed nitrite increasing the nitrite requirements of the system. The aim of this paper is the study of the causes which induce the system to decrease nitrogen removal efficiency. In this study, urban landfill leachate has been treated in an anammox Sequencing Batch Reactor (SBR) for 360 days. The anammox reactor treated on average 0.24 kgN m(-3) d(-1) obtaining nitrogen removal efficiencies up to 89%. The results demonstrated that i) a suitable influent nitrite to ammonium molar ratio is a crucial factor to avoid troubles in the anammox reactor performance; ii) an excess of nitrite implied nitrite accumulation in the reactor; iii) a lower nitrite supply than the necessary for the system could force a loss of specific anammox activity due to nitrite competition with denitrifiers. These results pointed out the importance of the previous partial-nitritation process control in order to obtain a correct influent nitrite to ammonium molar ratio for the anammox reactor. In addition, sudden variation of the leachate characteristics must be avoided.

Association between angiogenesis soluble factors and disease progression markers in chronic hepatitis C patients.

OBJECTIVES: Our objectives were to compare angiogenesis soluble factor (ASF) levels in chronic hepatitis C (CHC) patients and healthy individuals, and to investigate potential associations between ASF levels and both histological and biochemical markers of disease progression. METHOD: Thirty-six patients (69% males) positive for HCV-RNA by PCR analysis were included in the study. All patients underwent liver biopsy before treatment. Serum levels of vascular endothelial growth factor (VEGF), soluble Flt-1 and Flk-1 receptors, placental growth factor (PlGF), angiopoietin-2 (Ang-2) and soluble Tie-2 receptor were determined by ELISA. Fifteen healthy subjects were used as controls. RESULTS: In comparison to healthy individuals, CHC patients showed significantly increased serum levels of proangiogenic factors PlGF (22 +/- 5 vs. 18 +/- 8 pg/ml; p < 0.05), Ang-2 (1265 +/- 385 vs. 833 +/- 346 pg/ml; p < 0.005) and sFlt-1 (95 +/- 22 vs. 72 +/- 14 pg/ml; p < 0.0001). Interestingly, in CHC patients serum levels of VEGF and Tie-2 correlated with grade of inflammation, PlGF correlated with stage of fibrosis, and Flt-1 and Flk-1 correlated with serum transaminase levels (p < 0.05 in all cases). CONCLUSIONS: CHC patients showed increased serum levels of ASF, and a significant correlation was shown between serum levels of selected ASFs and grade of inflammation, stage of fibrosis, and transaminase levels.

[Hemangiopericytoma: report of 4 cases]. / Hemangiopericitoma: comunicación de 4 casos.

Hemangiopericytoma is an infrequent tumor of vascular origin derived from Zimmermann's pericyte cells. It is generally seen in adults of both sexes and its major risk is late recurrence, that occurs in up to 50% of cases. Its spread pattern is principally hematogenous. The management of the disease is similar to that of other sarcomas. Surgical treatment alone controls the disease in less than 30% of cases and the association of surgery and radiation therapy decrease the risk of local and distant recurrence. We report four cases of hemangiopericytomas, located in the prostate, retroperitoneum, supraclavicular space and lung. The four patients were treated with surgery and radiation therapy, three of them have had no evidence of recurrence after 1.5 to 6 years of follow up and the patient with the tumor located in the lung died one year after the operation.

Reevaluación del comportamiento del curso temporal del efecto de propofol descrito por el modelo farmacocinético de Schnider / Reevaluation of the time course of the effect of propofol described with the Schnider pharmacokinetic model

Introducción. La constante de primer orden que representa el equilibrio entre el plasma y el sitio efector (ke0) unifica la farmacocinética y la farmacodinamia de un fármaco. Esta constante se extrae para cada modelo farmacocinético específico y nos permite predecir el curso temporal del efecto en las perfusiones que usan TCI. El modelo PKPD de propofol publicado por Schnider et al. calcula un ke0 de 0,456min−1 con un correspondiente tiempo de efecto máximo (t peak) de 1,6min. El objetivo de este estudio fue reevaluar el valor del ke0 predicho por Schnider, con datos de una curva de efecto completa obtenida con control del BIS. Métodos. Pacientes programados para cirugía electiva, con monitorización estándar y BIS XP, recibieron una perfusión de propofol en modo TCI para alcanzar una diana plasmática de 12 μg/ml en 4min. Alcanzada esta, se detenía la perfusión y se obtenía una curva completa de efecto (pérdida y recuperación de la conciencia). El programa Anestfusor (Universidad de Chile) fue usado para controlar los infusores y calcular las concentraciones según el modelo farmacocinético de Schnider, y además guardar los datos de BIS cada segundo. La pérdida (LOC) y la recuperación de la conciencia (ROC) fue evaluada y registrada. Usando un método paramétrico tradicional con el programa ke0 objectfix de PKPD tools, se extrajo el ke0 de cada individuo y de la población. Resultados. Treinta y cinco pacientes adultos sanos (entre 18 y 90 años) fueron evaluados (21 varones y 14 mujeres) se obtuvo 1.001±182 datos EEG y sus correspondientes concentraciones plasmáticas calculadas. El ke0 poblacional obtenido fue de 0,144min−1±0,048, muy diferente del original (p<0,001). Este valor corresponde a un t peak de 2,45min. El rendimiento predictivo (Pk) para el nuevo modelo fue 0,9±0,03 pero solo 0,78±0,06 para el original (p<0,001). Partiendo de un BIS basal de 95,8±2,34, el BIS a LOC fue 77,48±9,6 y al ROC de 74,65±6,3 (p=0,027). La Ce calculada en el modelo original para LOC y ROC fue de 5,9±1,35 y 1,08±0,32 μg/ml respectivamente (p<0,001) y 2,3±0,63 y 2,0±0,65 μg/ml (p=ns) para el nuevo modelo. Los valores entre LOC/ROC fueron significativamente diferentes entre los 2 modelos (p<0,001). No se encontraron diferencias de sexo en el valor del ke0, pero sí se observó un impacto de la edad en el valor de ke0=0,26-(edad×0,0022) (p<0,05). Conclusiones. Las relaciones entre las concentraciones plasmáticas predichas por el modelo farmacocinético de Schnider y el efecto observado en el BIS fueron mejor caracterizadas con un valor de ke0 más pequeño (t1/2 ke0 más lento) que el del modelo original y con un impacto de la edad antes no descrito(AU)

Background. The first order plasma-effect-site equilibration rate constant (ke0) links the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. This constant, calculated for each specific PK drug model, allowed us to predict the course of the effect in a target controlled infusion (TCI). The PK-PD model of propofol, published by Schnider et al., calculated a ke0 value of 0.456min−1 and a corresponding time to peak effect (t peak) of 1.6min. The aim of this study was to reevaluate the ke0 value for the predicted Schnider model of propofol, with data from a complete effect curve obtained by monitoring the bispectral index (BIS). Methods. The study included 35 healthy adult patients (18-90 years) scheduled for elective surgery with standard monitoring and using the BIS XP® (Aspect), and who received a propofol infusion to reach a plasma target of 12 μg/ml in 4min. The infusion was then stopped, obtaining a complete effect curve when the patient woke up. The Anestfusor™ (University of Chile) software was used to control the infusion pumps, calculate the plasma concentration plotted by Schnider PK model, and to store the BIS data every second. Loss (LOC) and recovery (ROC) of consciousness was assessed and recorded. Using a traditional parametric method using the "ke0 Objective function" of the PK-PD tools for Excel, the individual and population ke0 was calculated. Predictive Smith tests (Pk) and Student t test were used for statistical analysis. A P<.05 indicated significance. Results. The evaluation included 21 male and 14 female patients (18 to 90 years). We obtained 1,001 (±182) EEG data and the corresponding calculated plasma concentration for each case. The population ke0 obtained was 0.144min−1 (SD±0.048), very different from the original model (P<.001). This value corresponds with a t peak of 2.45min. The predictive performance (Pk) for the new model was 0.9 (SD±0.03), but only 0.78 (SD±0.06) for the original (P<.001). With a baseline BIS of 95.8 (SD±2.34), the BIS at LOC was 77.48 (SD±9.6) and 74.65(SD±6.3) at ROC (P=.027). The calculated Ce in the original model at LOC and ROC were 5.9 (SD±1.35)/1.08 μg/ml (SD±0.32) (P<.001), respectively, and 2.3 (SD±0.63)/2.0 μg/ml (SD±0.65) (NS) for the new model. The values between LOC/ROC were significantly different between the 2 models (P<.001). No differences in ke0 value were found between males and females, but in the new model the ke0 was affected by age as a covariable (0.26-[age×0.0022]) (P<.05). Conclusions. The dynamic relationship between propofol plasma concentrations predicted by Schnider's pharmacokinetic model and its hypnotic effect measured with BIS was better characterized with a smaller ke0 value (slower t½ ke0) than that present in the original model, with an age effect also not described before(AU)

Asociación entre factores angiogénicos solubles y marcadores de progresión de la enfermedad en pacientes con hepatitis crónica C / Association between angiogenesis soluble factors and disease progression markers in chronic hepatitis C patients

Objetivos: el objetivo fue comparar los niveles de los factoressolubles de angiogenesis (FSA) en pacientes con hepatitis crónicaC (HCC) con individuos sanos, e investigar la asociación entre losniveles de FSA y los marcadores histológicos y bioquímicos de laenfermedad.Método: treinta y seis pacientes (69,4% hombres) positivospara el ARN-VHC fueron incluidos; a todos se les realizó biopsiahepática antes del tratamiento. Los niveles séricos del factor decrecimiento endotelial vascular (VEGF), de la forma soluble de susreceptores Flt-1 y Flk-1, del factor de crecimiento placentario(PlGF), de la angiopoyetina-2 (Ang-2) y de la forma soluble de sureceptor Tie-2 fueron determinados por ELISA. Se analizarontambién 15 controles sanos.Resultados: al comparar los pacientes con HCC y los controlesse observó una elevación significativa en los niveles de PlGF(22 ± 5 vs. 18 ± 8 pg/ml; p < 0,05), Ang-2 (1265 ± 385 vs. 833± 346 pg/ml; p < 0,005) y sFlt-1 (95 ± 22 vs. 72 ± 14 pg/ml; p< 0,0001). Se observó una correlación entre el VEGF y el Tie-2con el grado de inflamación; entre PlGF y el estadio de la fibrosis;y entre Flt-1 y Flk-1 y los niveles de transaminasas (p < 0,05 entodos los casos).Conclusiones: en pacientes con HCC se observó una elevaciónsignificativa de los FSA demostrándose una correlación significativaentre los niveles séricos de ciertos FSA y el grado de inflamación,el estadio de fibrosis y los niveles de transaminasas

Objectives: our objectives were to compare angiogenesis solublefactor (ASF) levels in chronic hepatitis C (CHC) patients andhealthy individuals, and to investigate potential associations betweenASF levels and both histological and biochemical markersof disease progression.Method: thirty-six patients (69% males) positive for HCVRNAby PCR analysis were included in the study. All patients underwentliver biopsy before treatment. Serum levels of vascularendothelial growth factor (VEGF), soluble Flt-1 and Flk-1 receptors,placental growth factor (PlGF), angiopoietin-2 (Ang-2) andsoluble Tie-2 receptor were determined by ELISA. Fifteen healthysubjects were used as controls.Results: in comparison to healthy individuals, CHC patientsshowed significantly increased serum levels of proangiogenic factorsPlGF (22 ± 5 vs. 18 ± 8 pg/ml; p < 0.05), Ang-2 (1265 ±385 vs. 833 ± 346 pg/ml; p < 0.005) and sFlt-1 (95 ± 22 vs. 72± 14 pg/ml; p < 0.0001). Interestingly, in CHC patients serumlevels of VEGF and Tie-2 correlated with grade of inflammation,PlGF correlated with stage of fibrosis, and Flt-1 and Flk-1 correlatedwith serum transaminase levels (p < 0.05 in all cases).Conclusions: CHC patients showed increased serum levels ofASF, and a significant correlation was shown between serum levelsof selected ASFs and grade of inflammation, stage of fibrosis,and transaminase levels