Transición desde la asistencia pediátrica a la adulta en pacientes con mucopolisacaridosis / Transition from paediatric care to adult care for patients with mucopolysaccharidosis

Las mucopolisacaridosis son enfermedades multisistémicas que requieren para su atención equipos multidisciplinares amplios. Por ello se hacen necesarias recomendaciones específicas para la transición de la edad pediátrica a la adulta en este grupo de pacientes. Para la superación de las barreras que pudieran surgir durante la transición, los autores consideran esencial realizar un plan flexible con un coordinador de todo el proceso, sistematizar la información a través de un informe de alta pediátrico estandarizado, formar al paciente y su familia sobre la enfermedad y mostrar las características del sistema sanitario en esta nueva etapa. El objetivo final es que al concluir la transición a la edad adulta se haya maximizado la autonomía y el potencial de desarrollo del paciente y este reciba una atención sanitaria adecuada durante dicho periodo de transición (AU)

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition (AU)

Transition from paediatric care to adult care for patients with mucopolysaccharidosis. / Transición desde la asistencia pediátrica a la adulta en pacientes con mucopolisacaridosis.

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition.

Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals.

Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. The most prevalent group of IEMs was amino acid disorders, with 108 (21.6%) patients diagnosed with phenylketonuria. Lysosomal storage disorders were the second group, in which 32 (6.4%) and 25 (5%) patients had Fabry disease and Gaucher disease respectively. The great clinical heterogeneity, the significant delay in diagnosis after symptom onset, the existence of some degree of physical dependence in a great number of patients, the need for a multidisciplinary and coordinated approach, and the lack of specific drug treatment are common features in this group of conditions.

Lupus eritematoso cutáneo subagudo secundario a tratamiento con diuréticos tiazídicos / Thiazide diuretics induce subacute cutaneous lupus erythematosus

No disponible

Distribución del grosor íntima-media carotídeo en función de la estratificación del riesgo cardiovascular según las funciones de Framingham-REGICOR y SCORE / Carotid intima-media thickness distribution according to the stratification of cardiovascular risk by means of Framingham-REGICOR and score function charts

Objetivos: El grosor íntima-media carotídeo (GIMc) ha sido propuesto como complemento a las escalas de cálculo del riesgo cardiovascular (RCV). El objetivo del presente estudio es describir la asociación entre el GIMc y el grado de RCV estimado según las funciones SCORE y Framingham-REGICOR. Método: Estudio observacional, transversal de una cohorte de 362 pacientes hipertensos. Se les realizó de forma sistemática una evaluación clínico-epidemiológica, analítica, ultrasonográfica y una estimación del RCV según las tablas SCORE y Framingham-REGICOR. Mediante el software SPSS (versión 20,0), se llevó a cabo el análisis de datos utilizando los análisis estadísticos t de Student, chi-cuadrado, coeficiente de Pearson y el análisis de la varianza (ANOVA). Resultados: Se demuestran diferencias significativas en la media de GIMc entre los pacientes con RCV estimado bajo (GIMc: 0,73 mm en ambas funciones) y los de riesgo moderado (GIMc: 0,89 y 0,85 mm según SCORE y Framingham-REGICOR) o elevado (0,88 y 0,87 mm respectivamente). No existen diferencias entre los de riesgo moderado y elevado. El GIMc se correlaciona positivamente con el valor de RCV estimado mediante las tablas SCORE (r = 0,421; p < 0,01), así como con la función Framingham-REGICOR (r = 0,363; p < 0,01). Conclusiones: El GIMc se correlaciona positivamente con el grado de RCV estimado mediante las funciones SCORE y Framingham-REGICOR. Aquellos pacientes con riesgo moderado presentan un GIMc similar al de aquellos con riesgo elevado. Se destaca la utilidad del estudio ultrasonográfico carotídeo para la detección precoz de lesión silente en pacientes con RCV moderado

Background: Carotid intima-media thickness (cIMT) has been suggested as a further tool for risk function charts. The aim of this study was to describethe relationship between cIMT and cardiovascular risk (CVR) estimation according to Framingham-REGICOR and SCORE equations. Methods: Observational, cross-sectional cohort study from 362 hypertensive subjects. Demographic and clinical information were collected as well as laboratory, ultrasonographic and CVR estimation by the Framingham-REGICOR and SCORE functions. Statistical analysis was performed using SPSS software (version 20,0). To analyze the data, statistical tests such as Chi-square, T-test, ANOVA, and Pearson correlation coefficient were used. Results:According to both functions, differences on mean cIMT were found between low CVR group and intermediate to high groups. No differences were found between intermediate and high risk groups (cIMT: 0,73 mm low risk patients vs. 0,89 or 0,88 mm respectively according to SCORE function and cIMT: 0,73 vs. 0,85 or 0,87 mm respectively according to Framingham-REGICOR function). cIMT correlated positively with CVR estimation according to both SCORE (r = 0,421; P<.01), and Framingham-REGICOR functions (r = 0,363; P<.01). Conclusions: cIMT correlates positively with CVR estimated by SCORE and Framingham-REGICOR functions. cIMT in those subjects at intermediate risk is similar to those at high risk. Our findings highlight the importance of carotid ultrasound in identifying silent target-organ damage in those patients at intermediate CVR

Comparación del valor predictivo cardiovascular de MDRD y CKD-EPI en la estimación de la enfermedad renal crónica / Comparison of the cardiovascular predictive value of MDRD and CKD-EPI in estimating chronic kidney disease

Objetivo. Comparar el valor predictivo, en el pronóstico cardiovascular, de las fórmulas más empleadas para la estimación del filtrado glomerular en pacientes hipertensos. Material y métodos. Se diseñó un estudio de cohortes retrospectivo, que incluyó los 405 pacientes diagnosticados de HTA esencial que fueron remitidos a la Unidad de Hipertensión y Riesgo Vascular, desde atención primaria, entre el 1 de enero de 1998 y el 31 de agosto de 1999 y a los que se les realizó simultáneamente un estudio de MAPA, análisis de sangre y orina y ecocardiográfico. Se realizó el seguimiento a lo largo de 12,5 años (mediana [± RiQ]: 10,61 [± 3,11] años) y se registraron 174 eventos. Resultados. Se incluyeron 405 pacientes (53,8% mujeres), con una edad media de 55,5 años. El filtrado glomerular estimado según las fórmulas MDRD y CKD-EPI fue de 73,9 ± 2,6 ml/min/1,73 m2 y 76,9 ± 2,2 ml/min/1,73 m2, respectivamente. La prevalencia de enfermedad renal crónica fue del 31,6 y del 23,9%, respectivamente. El uso de la ecuación CKD-EPI obligó a reclasificar al 22,9% de los pacientes. La RTI [IC 95%] para la enfermedad renal crónica identificada por la ecuación MDRD fue de 2,4 [1,8-3,3], y para el cálculo con CKD-EPI fue de 2,5 [1,8-3,3]). Conclusiones. Ambas fórmulas estiman magnitudes semejantes de función renal, aunque la ecuación CKD-EPI evita algunos falsos positivos, y ambas tienen similar valor pronóstico en pacientes tanto de alto como bajo riesgo cardiovascular (AU)

Objective. To assess predictive value of the cardiovascular prognosis by comparing the two most used formulas for the estimation of glomerular filtration rate in hypertensive patients. Material and methods. A retrospective cohort study was designed that included 405 patients diagnosed with essential hypertension. The patients were referred from Primary Care to the Hypertension and Vascular Risk Unit between January 1, 1998 and August 31, 1999. Blood pressure measurements, blood and urine analysis, and echocardiography were simultaneously performed. They were followed up for 12.5 years (mean [± IQR]: 10.61 [± 3.11] years) and 174 events were recorded. Results. The study included 405 patients (53.8% women), with a mean age of 55.5 years. The estimated glomerular filtration rate according to the MDRD and CKD-EPI equations was 73.9 ± 2.6 mL/min/1.73 m2 and 76.9 ± 2.2 mL/min/1.73 m2, respectively. The prevalence of chronic kidney disease was 31.6% and 23.9%, respectively. Using the CKD-EPI equation led to the re-classification of 22.9% of patients. The incidence rate ratio (IRR [95% CI] for chronic kidney disease identified by the MDRD equation was 2.4 [1.8-3.3], and for the CKD-EPI calculation it was 2.5 [1.8 to 3.3]). Conclusions. Both equations estimate similar magnitudes of renal function, although the CKD-EPI equation has less false positives, and both have similar prognostic values in patients at high cardiovascular risk as well those at low risk (AU)

[Carotid intima-media thickness distribution according to the stratification of cardiovascular risk by means of Framingham-REGICOR and score function charts]. / Distribución del grosor íntima-media carotídeo en función de la estratificación del riesgo cardiovascular según las funciones de Framingham-REGICOR y SCORE.

BACKGROUND: Carotid intima-media thickness (cIMT) has been suggested as a further tool for risk function charts. The aim of this study was to describethe relationship between cIMT and cardiovascular risk (CVR) estimation according to Framingham-REGICOR and SCORE equations. METHODS: Observational, cross-sectional cohort study from 362 hypertensive subjects. Demographic and clinical information were collected as well as laboratory, ultrasonographic and CVR estimation by the Framingham-REGICOR and SCORE functions. Statistical analysis was performed using SPSS software (version 20,0). To analyze the data, statistical tests such as Chi-square, T-test, ANOVA, and Pearson correlation coefficient were used. RESULTS: According to both functions, differences on mean cIMT were found between low CVR group and intermediate to high groups. No differences were found between intermediate and high risk groups (cIMT: 0,73mm low risk patients vs. 0,89 or 0,88mm respectively according to SCORE function and cIMT: 0,73 vs. 0,85 or 0,87mm respectively according to Framingham-REGICOR function). cIMT correlated positively with CVR estimation according to both SCORE (r=0,421; P<.01), and Framingham-REGICOR functions (r=0,363; P<.01). CONCLUSIONS: cIMT correlates positively with CVR estimated by SCORE and Framingham-REGICOR functions. cIMT in those subjects at intermediate risk is similar to those at high risk. Our findings highlight the importance of carotid ultrasound in identifying silent target-organ damage in those patients at intermediate CVR.

[Comparison of the cardiovascular predictive value of MDRD and CKD-EPI in estimating chronic kidney disease]. / Comparación del valor predictivo cardiovascular de MDRD y CKD-EPI en la estimación de la enfermedad renal crónica.

OBJECTIVE: To assess predictive value of the cardiovascular prognosis by comparing the two most used formulas for the estimation of glomerular filtration rate in hypertensive patients. MATERIAL AND METHODS: A retrospective cohort study was designed that included 405 patients diagnosed with essential hypertension. The patients were referred from Primary Care to the Hypertension and Vascular Risk Unit between January 1, 1998 and August 31, 1999. Blood pressure measurements, blood and urine analysis, and echocardiography were simultaneously performed. They were followed up for 12.5 years (mean [± IQR]: 10.61 [± 3.11] years) and 174 events were recorded. RESULTS: The study included 405 patients (53.8% women), with a mean age of 55.5 years. The estimated glomerular filtration rate according to the MDRD and CKD-EPI equations was 73.9±2.6 mL/min/1.73m(2) and 76.9±2.2 mL/min/1.73m(2), respectively. The prevalence of chronic kidney disease was 31.6% and 23.9%, respectively. Using the CKD-EPI equation led to the re-classification of 22.9% of patients. The incidence rate ratio (IRR [95%CI] for chronic kidney disease identified by the MDRD equation was 2.4 [1.8-3.3], and for the CKD-EPI calculation it was 2.5 [1.8 to 3.3]). CONCLUSIONS: Both equations estimate similar magnitudes of renal function, although the CKD-EPI equation has less false positives, and both have similar prognostic values in patients at high cardiovascular risk as well those at low risk.

Hipertrofia ventricular izquierda y variación circadiana de la presión arterial / Left ventricular hypertrophy and circadian variation in blood pressure

Antecedentes y objetivos: Son múltiples los estudios que avalan el papel pronóstico que han mostrado tanto la presión arterial (PA) ambulatoria como la hipertrofia ventricular izquierda (HVI) en el paciente hipertenso. Por ello, nos planteamos evaluar la correlación existente entre determinados parámetros de la PA ambulatoria y la masa ventricular izquierda (MVI) medida por ecocardiografía, en una muestra de pacientes hipertensos. Material y métodos Se diseñó un estudio transversal retrospectivo, que incluyó a 405 pacientes (53,8% mujeres), con una edad media de 55,5 años, diagnosticados de HTA esencial, remitidos a la Unidad de HTA y Riesgo Vascular, desde atención primaria, entre el 1 de enero de 1998 y el 31 de agosto de 1999. En todos los casos se realizó una evaluación clínica y biológica (según protocolo estandarizado), estudio ecocardiográfico y MAPA de 24 h (monitor Space Labs 90207).Resultados La MAPA demostró un mal control de la HTA en 320 pacientes (79%); la profundidad de la PA sistólica fue del 10,6 ± 0,9%. La prevalencia de perfil dipper fue del 43,8%, del dipper-extremo 13,4%, del no dipper 30,2% y del riser 12,6%. Se identificó a 248 pacientes (61,23%) con HVI. El aumento de la PA ambulatoria nocturna se asoció con un incremento de la MVI (p < 0,0001) y se objetivó una correlación estadísticamente significativa y negativa entre la disminución de la profundidad de la PA y el incremento del índice de MVI (p < 0,0001).Conclusión El incremento de la MVI se asocia con HTA nocturna y disminución de la profundidad nocturna de la PA (AU)

Background and objectives: Multiple studies support the prognostic role of both ambulatory blood pressure (BP) monitoring and left ventricular hypertrophy (LVH) in patients with hypertension. Consequently, we evaluated the correlation between certain ambulatory BP monitoring parameters and left ventricular mass (LVM) measured by echocardiography in a sample of hypertensive patients. Material and methods: A cross sectional, retrospective study was performed in 405 patients(53.8% women; mean age, 55.5 years), diagnosed with essential hypertension and referred to the Hypertension and Vascular Risk Unit by their primary care centers between 1 January,1998 and 31 August, 1999. All patients underwent clinical and biological evaluation (using a standardized protocol), echocardiography, and 24-hour ambulatory BP monitoring (SaceLabs90207).Results: Ambulatory BP monitoring revealed poor BP control in 320 patients (79%); the meandip in systolic BP was 10.6 ± 0.9%. The dipper pattern was observed in 43.8%, the extreme dipper pattern in 13.4%, the non-dipper pattern in 30.2%, and the riser pattern in 12.6%. Left ventricular hypertrophy was identified in 248 patients (61.23%). An increase in ambulatory nocturnal BP was associated with an increase in LVM (p < 0.0001) and a statistically significant negative correlation was observed between the drop in BP and the increase in LVM (P<.0001).Conclusion: An increase in LVM was associated with nocturnal hypertension and a decrease in the nocturnal drop in BP (AU)

[Epidemiological events related to decompensated heart failure]. / Factores epidemiológicos asociados a la hospitalización por descompensación de la insuficiencia cardiaca.

OBJECTIVE: The present study aimed to evaluate the profile of patients with decompensated heart failure hospitalized in a tertiary hospital. METHODS: It was designed an observational and retrospective study where data from clinical records of patients suffering from heart failure along 2005 were registered randomly. RESULTS: 209 patients were collected (average age: 78.6 +/- 9.1; male: 52.4%) with a comorbidity rate of 87.55%. Almost one third of them have not stimation of systolic function and among the others 72.4% have it preserved. Most of decompensated were due to respiratory infections. Ischemic-hipertensive cardiopathy was the most frequent aetiology of systolic disfunction. Average stay was 12.9 days with a mortality rate of 9.56%. Its main risk factors were advanced stages in NYHA od Red Cross scales, as so as dementia or ictus. CONCLUSIONS: The present study shows a patient hospitalized for decompensated heart failure roughly different from that one reported at clinical trials. It makes difficult to apply therapeutical interventions, previously well documented to be useful.

Tumoración craneal y paraparesia de extremidades inferiores / No disponible

Introducción: Habitualmente el carcinomamicrocítico de pulmón (oat-cell) debuta con sintomatologíarespiratoria y/o hallazgos radiológicospulmonares.Caso clínico: El caso clínico presentado muestraun paciente con una masa craneal metastásica ysíndrome de compresión medular como debut de unoat-cell pulmonar.Conclusiones: Es necesario un alto índice desospecha clínica para detectar precozmente los carcinomasmicrocíticos de pulmón en estadío limitado.Sin embargo, casos como el aportado reflejan elcomportamiento agresivo del mismo con un elevadoporcentaje de estadíos diseminados al diagnóstico yelevada morbimortalidad

Introduction: Small cell lung cancer (oat.cellcarcinoma) comes up usually with respiratorysymptoms and/or radiological findings.Clinical case: This clinical case correspondsto a patient with a metastatic skull mass and medullarycompression syndrome as a debut of an oatcell lung cancer.Conclusions: A very marked suspicion is necessaryfor the clinical early diagnosis of small celllung cancer with limited disease. Nevertheless, casesas the one reported here manifest its aggressiveness,with a high rate of dissemination at diagnosisand a high morbimortality (AU)

[Epidemiology of heart failure. Ratio of epidemic]. / Epidemiología de la insuficiencia cardiaca. Proporciones de epidemia.

The Heart Failure is a complex sindrom with a high prevalence in the population, being about 10% in older than 70 years and it is continuosly increasing . Its incidence in persons older than 65 years is about 1% per year. In developed countries it is the first cause of hospitalitation in older than 65 years, supposing the 5% of total admissions and it is increasing every year. The most of authors recognise that the numbers reach values of epidemic, although it is true that it is difficult to determine and cuantify due to its complexity. Although the supervivence has improved in last years, it continues being in a bad pronostic with a mortality about 50% after 5 years approximately of the diagnostic . In order to its high prevalence and its high rate of admissions-readmissions it supposes a problem of public health due to high assistance work. Globally it is estimated that the direct costs of heart failure suppose 1-2 % of healthy cost of developed countries.

[Pacemaker endocarditis]. / Endocarditis del marcapasos.

Pacemaker endocarditis is a rare but serious complication of permanent transvenous pacing. The most common presentation is fever syndrome or gram positive bacteremia. For the diagnostic it is important to performed blood cultures and an echocardiography. A retrospective study included the cases of pacemaker endocarditis diagnosed in the Internal Medicine Department of our Hospital between 1989-2003. Six patients were included. Repeated manipulation of the system and diabetes were the most frequent risk factors. The most frequently detected causative microorganisms were Staphylococci. In spite of the low sensitivity of the transthoracic echocardiography in expert hands it can improve, in this series it places in 66 %. Surgical treatment with cardiopulmonary bypass and implantation of a new system was performed in the same intervention in all patients. None relapsed and the overall mortality was 17%.

Endocarditis del marcapasos / Pacemaker endocarditis

La endocarditis del marcapasos es una complicación poco frecuente pero grave. La forma más frecuente de presentación es como síndrome febril y/o bacteriemia por gérmenes gram positivos. Dos elementos claves para el diagnóstico son los hemocultivos y el ecocardiograma. Se realiza un análisis retrospectivo de los pacientes con endocarditis del marcapasos ingresados en el Servicio de Medicina Interna de nuestro hospital entre 1989-2003. Se incluyeron 6 pacientes. En este estudio la manipulación repetida del sistema y la diabetes mellitus fueron los factores de riesgo más frecuentes. Los microorganismos más frecuentemente implicados fueron los Staphylococcus spp. A pesar de la menor sensibilidad del ecocardiograma transtorácico, en manos expertas puede mejorar su rendimiento, en esta serie se sitúa en el 66%. Se realizó extracción mediante cirugía extracorpórea e implantación de un nuevo sistema en la misma intervención en todos, sin ningún caso de recidiva y con una mortalidad del 17%

Pacemaker endocarditis is a rare but serious complication of permanent transvenous pacing. The most common presentation is fever syndrom or gram positive bacteremia. For the diagnostic it is important to performed blood cultures and an echocardiography. A retrospective study included the cases of pacemaker endocarditis diagnosed in the Internal Medicine Department of our Hospital between 1989-2003. Six patients were included. Repeated manipulation of the system and diabetes were the most frequent risk factors. The most frequently detected causative microorganisms were Staphylococci. In spite of the low sensitivity of the transthoracic echocardiography in expert hands it can improve, in this series it places in 66 %. Surgical treatment with cardiopulmonar bypass and implantation of a new system was performed in the same intervention in all patients. None relapsed and the overall mortality was 17%

[Pacemaker endocarditis]. / Endocarditis del marcapasos.

In the last years an increment has taken place in the pacemaker and implantable cardioverter-defibrillator indications that will have as consequence an increase of the prevalence of endocarditis associated to intravascular devices, for what acquires special relevance for the clinician to know this entity and to include it in his differential diagnoses. The objective of this article is to describe the epidemiology, clinic characteristics, diagnosis, treatment and outcome of the pacemaker endocarditis.

Endocarditis del marcapasos / Pacemaker endocarditis

En los últimos años se ha producido un incremento en las indicaciones de marcapasos y desfibriladores autoimplantables que tendrá como consecuencia un aumento de la prevalencia de la endocarditis asociada a dispositivos intravasculares, por lo que adquiere especial relevancia para el clínico conocer esta entidad e incluirla en sus diagnósticos diferenciales. El objetivo de este articulo es describir la epidemiología, características clínicas, diagnóstico, tratamiento y pronóstico de la endocarditis asociada al marcapasos

In the last years an increment has taken place in the pacemaker and implantable cardioverter-defibrillator indications that will have as consequence an increase of the prevalencia of the endocarditis associated to intravascular devices, for what acquires special relevance for the clinical one to know this entity and to include it in his differential diagnoses. The objetive of this article is to describe the epidemiology, clinic characteristics, diagnosis, treatment and outcome of the pacemaker endocarditis

Effect of iron and manganese on hydroxyl radical production by 6-hydroxydopamine: mediation of antioxidants.

6-Hydroxydopamine (6-OHDA) neurotoxicity has often been related to the generation of free radicals. Here we examined the effect of the presence of iron (Fe(2+) and Fe(3+)) and manganese and the mediation of ascorbate, L-cysteine (CySH), glutathione (GSH), and N-acetyl-CySH on hydroxyl radical (*OH) production during 6-OHDA autoxidation. In vitro, the presence of 800 nM iron increased (> 100%) the production of *OH by 5 microM 6-OHDA while Mn(2+) caused a significant reduction (72%). The presence of ascorbate (100 microM) induced a continuous generation of *OH while the presence of sulfhydryl reductants (100 microM) limited this production to the first minutes of the reaction. In general, the combined action of metal + antioxidant increased the *OH production, this effect being particularly significant (> 400%) with iron + ascorbate. In vivo, tyrosine hydroxylase immunohistochemistry revealed that intrastriatal injections of rats with 6-OHDA (30 nmol) + ascorbate (600 nmol), 6-OHDA + ascorbate + Fe(2+) (5 nmol), and 6-OHDA + ascorbate + Mn(2+) (5 nmol) caused large striatal lesions, which were markedly reduced (60%) by the substitution of ascorbate by CySH. Injections of Fe(2+) or Mn(2+) alone showed no significant difference to those of saline. These results clearly demonstrate the role of ascorbate as an essential element for the neurotoxicity of 6-OHDA, as well as the diminishing action of sulfhydryl reductants, and the negligible effect of iron and manganese on 6-OHDA neurotoxicity.