Análisis de flujos de substancias: una herramienta aplicada a la evaluación de riesgos por dioxinas en la provincia de Tarragona.

Las dibenzo-p-dioxinas policloradas (PCDD) y dibenzofuranos (PCDF) son compuestos organoclorados tóxicos formados como productos secundarios de diversos procesos de la industria química y de combustión. La posición y el número de átomos de cloro en los anillos de benceno de las moléculas de PCDD/Fs conduce a 75 compuestos individuales o congéneres de PCDDs y 135 de PCDFs. Su elevado carácter lipofílico favorece que se acumulen en los suelos, sedimentos, plantas, tejido adiposo humano y animal. A partir de estudios de diversos episodios de contaminación, El Instituto de Medicina Norteamericano ha tenido especial evidencia de que la exposición a PCDD/Fs a través de la cadena alimenticia e inhalación provoca en el hombre diversos síntomas de toxicidad: cutáneos, sistémicos y neuro-psíquicos. En cuanto a los efectos carcinogénicos de la exposición al congénere TCCC, la Agencia Internacional para la Investigación del Cáncer (IARC) reclasificó esta substancia en 1997 desde el grupo II de su clasificación: "probable agente cancerígeno en humanos" al grupo I: "conocido agente cancerígeno en humanos". Se ha acordado expresar la concentración de una mezcla de congéneres en unidades equivalentes tóxicas internacionales de la 2,3,7,8-TCC, lo cual da una medidad de su potencial tóxico. Esta se calcula como resultado de sumar las concentraciones de cada congénere, que se obtienen a partir de los factores de equivalencia tóxica (TEFs).En los últimos años ha habido un desarrollo notable de métodos que han buscado ser una herramienta eficaz en la toma de decisiones en la gestión medioambiental. Los métodos Funciones de Daño son los más generalizados. Estos utilizan la variable concentración como cauce para determinar el impacto ocasionado por la contaminación. Sin embargo, el presente trabajo ha buscado ser una alternativa respecto a los métodos anteriores al incorporar la variable flujo de contaminantes como instrumento de sus cálculos. Se ha desarrollado y aplicado a la provincia de Tarragona una metodología de gestión medioambiental basada en las siguientes cuatro etapas: a) Realizar un inventario de fuentes de PCDD/Fs al aire, suelo y agua en la provincia de Tarragona: para determinar las cantidades de PCDD/Fs emitidas por las fuentes identificadas no ha sido posible en bastantes casos disponer de datos procedentes del propio foco emisor. En ese caso se ha recurrido a una extrapolación: el uso de factores de emisión y concentraciones procedentes de la bibliografía, y que son representativas de la clase industrial en estudio. Las emisiones totales de estimadas durante 1999 han sido una media de 175,7 g I-TEQ/año. b) La utilización del Análisis de Flujos de Substancias (AFS) ha llevado a compartimentalizar el sistema provincia de Tarragona en 30 subsistemas, con 88 flujos de entrada, salida e internos entre ellos. Se ha estimado el valor de todos los flujos de PCDD/Fs no medidos y se ha reconciliado -esto es: optimizado la incertidumbre- el valor de 32 flujos medidos. Una reducción completa de las emisiones industriales de PCDD/Fs conlleva una reducción del 1,7% en el flujo de acumulación en humanos.c) La evaluación de riesgos permite conocer los impactos debidos a cambios en la calidad medioambiental. El presente trabajo se ha centrado en impactos sobre la salud de la población, y dentro de ellos en los riesgos cancerígenos. La evaluación de riesgos ha concluido que la reducción del índice de riesgo cancerígeno anual en la población de la provincia de Tarragona, debida a una reducción total de las emisiones de dioxinas al aire en una específica planta industrial tiene una media de 0,30 casos/año. d) El Análisis Coste-Beneficio (ACB) ha concluido que en el caso americano, el proyecto de reducción de contaminación en la planta industrial es viable con una probabilidad del 15%, y en un contexto europeo no es en ningún caso viable.Polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) are ubitiquous organic pollutants. They are generated in small quantities as by-products of several chemical and combustion processes. The number and position of chlorine atoms at the benzene rings of PCDD/Fs molecules lead to 75 PCDDs individual compounds or congeners and 135 PCDFs congeners. Their high lypophilic character is the cause of their tedency to accumulate in soils, sediments, plants, animal and human adipose tissue. From several studies about impacts on humans to the congener 2,3,7,8-TCDD, the American Insitute of Medicine has described that there is evidence that exposure to this compound through the feeding chain and inhalation induces in humans several symptoms of toxicity: cloracne, systemic and neropsyquic. Respect to carcinogenic effects, the International Agency of Research on Cancer (IARC) reclassified in 1997 this congener from the group II of its classification: "a probable carcinogenic agent in humans" to the group I: "known carcinogenic agent in humans". Concentration of a mixture of congeners is the result of adding up concentrations of each congener, and it is expressed in international toxic equivalents of the 2,3,7,8-TCDD (I-TEQ), which gives a toxic potential of the mixture. It is obtained from the toxic equivalent factors (TEF).During the last decade there has been an important development of methodologies which have searched to be an efficient tool within environmental management. Damage Function methods are the most usual. These use the variable concentration as the way to fix the impact by pollution. Nevertheless, the present study has looked to be an alternative, by adding the variable flow of pollutants as a tool for its calculations. Then, it has been developed and applied to the area Tarragona province an environmental management methodolgy based on the following four steps:a) Drawing up an inventory of PCDD/Fs sources to air, soil and water in Tarragona province. In order to know amounts of PCDD/Fs released to the environment by the identified sources, it has not been possible in many cases to have data coming from the own focus. In these cases, it has been resorted to an extrapolation: the use of emission factors and concentrations, which come from the literature and are representative of the industrial class in study. Global estimated emissions to air, land and water in 1999 were a mean of 175,7 g I-TEQ/year.b) The use of Substance Flow Analysis (SFA) has led to compartimentalize Tarragona province system into 30 environmental subsystems, with 88 input, ouptut and internal flows among them. It has been estimated the value of all non-measured flows, and reconciliated -i.e.: opitmization of uncertainty- of 32 measured flows. A complete reduction of industrial PCDD/Fs emissions implies a 1,7% reduction of the flow "accumulation in human adipose tissue".c) A risk assessment allows to estimate the impacts on population due to changes in environmental quality. The present study has focused on human health impacts, and inside them on carcinogenic risk, as a result of a reduction of PCDD/Fs emissions to air. The risk assessment has concluded that the reduction of the annual cancer risk rate for all the population, as a result of a total reduction of dioxin emissions to air in a specific industrial plant, has a meanvalue of 0,30 cases/year.d) As a final step, a Cost-Benefit Analysis (ACB) has concluded that in an american environment, the project of PCDD/Fs reduction in the plant is feasible only with a 15% probability, while in a european environment the project is in any way viable

Validation of a Spanish version of the Leicester Cough Questionnaire in cystic fibrosis

Bronchiectasis; Quality of life; Respiratory diseaseBronquiectasia; Calidad de vida; Enfermedad respiratoriaBronquiectàsia; Qualitat de vida; Malaltia respiratòriaCough is a main symptom in cystic fibrosis (CF). We aim to validate a Spanish version of the Leicester Cough Questionnaire (LCQ-Sp) to measure the impact of cough in CF bronchiectasis. A prospective longitudinal multicentre study was performed. Internal consistency and score changes over a 15-day period in stable state were assessed to analyse reliability. Concurrent validity was analysed by correlation with Saint George’s Respiratory Questionnaire (SGRQ) and convergent validity by assessing the association with clinical variables. Changes in scores between stable state and the first exacerbation were assessed to analyse responsiveness. 132 patients (29.73 ± 10.52 years) were enrolled in four hospitals. Internal consistency was high for the total score and good for the three domains (Cronbach’s α 0.81–0.93). The test–retest reliability showed an intraclass correlation coefficient of 0.86 for the total score. The correlation between LCQ-Sp and SGRQ scores was −0.74. The LCQ-Sp score negatively correlated with sputum volume, and the mean score decreased at the beginning of exacerbations (16.04±3.81 vs 13.91±4.29) with a large effect size. The LCQ-Sp is a reliable, repeatable and responsive instrument to assess the impact of cough in CF bronchiectasis and is responsive to change in the event of exacerbations.The author(s) received no financial support for the research, authorship, and/or publication of this article

Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation

BACKGROUND: Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of (18)F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model. METHODS: Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta. RESULTS: Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity. CONCLUSION: PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion

MRI Discriminates Thrombus Composition and ST Resolution after Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

Histological composition of material obtained by thrombus aspiration during percutaneous coronary intervention (PCI) in patients with ST-segment elevation acute myocardial infarction (STEMI) is highly variable. We aimed to characterize this material using magnetic resonance imaging (MRI) and to correlate MRI findings with the success of PCI in terms of ST-segment resolution. Thrombus aspiration during primary or rescue PCI was attempted in 100 consecutive STEMI patients, of whom enough material for MRI was obtained in 59. MR images were obtained at 9.4T and T1 and T2 values were measured. Patients with (n = 31) and without (n = 28) adequate ST resolution 120 min after PCI (≥70% of pre-PCI value) had similar baseline characteristics except for a higher prevalence of diabetes mellitus in the latter (10 vs. 43%, p = 0.003). T1 values were similar in both groups (1248±112 vs. 1307±85 ms, respectively, p = 0.7). T2 values averaged 31.2±10.3 and 36.6±12.2 ms; in thrombus from patients with and without adequate ST resolution (p = 0.09). After adjusting for diabetes and other baseline characteristics, lower T2 values were significantly associated with inadequate ST resolution (odds ratio for 1 ms increase 1.08, CI 95% 1.01–1.16, p = 0.027). Histology classified thrombus in 3 groups: coagulated blood (n = 38), fibrin rich (n = 9) and lipid-rich (n = 3). Thrombi composed mostly of coagulated blood were characterized as being of short (n = 10), intermediate (n = 15) or long evolution (n = 13), T2 values being 34.0±13.2, 31.9±8.3 and 31.5±7.9 ms respectively (p = NS). In this subgroup, T2 was significantly higher in specimens from patients with inadequate perfusion (35.9±10.3 versus 28.6±6.7 ms, p = 0.02). This can be of clinical interest as it provides information on the probability of adequate ST resolution, a surrogate for effective myocardial reperfusion

XAF1 as a modifier of p53 function and cancer susceptibility

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers.Fil: Pinto, Emilia M.. St. Jude Children's Research Hospital; Estados UnidosFil: Figueiredo, Bonald C.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Chen, Wenan. St. Jude Children's Research Hospital; Estados UnidosFil: Galvao, Henrique C.R.. Hospital de Câncer de Barretos; BrasilFil: Formiga, Maria Nirvana. A.c.camargo Cancer Center; BrasilFil: Fragoso, Maria Candida B.V.. Universidade de Sao Paulo; BrasilFil: Ashton Prolla, Patricia. Universidade Federal do Rio Grande do Sul; BrasilFil: Ribeiro, Enilze M.S.F.. Universidade Federal do Paraná; BrasilFil: Felix, Gabriela. Universidade Federal da Bahia; BrasilFil: Costa, Tatiana E.B.. Hospital Infantil Joana de Gusmao; BrasilFil: Savage, Sharon A.. National Cancer Institute; Estados UnidosFil: Yeager, Meredith. National Cancer Institute; Estados UnidosFil: Palmero, Edenir I.. Hospital de Câncer de Barretos; BrasilFil: Volc, Sahlua. Hospital de Câncer de Barretos; BrasilFil: Salvador, Hector. Hospital Sant Joan de Deu Barcelona; EspañaFil: Fuster Soler, Jose Luis. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. St. Jude Children's Research Hospital; Estados UnidosFil: Vaur, Dominique. Comprehensive Cancer Center François Baclesse; FranciaFil: Odone Filho, Vicente. Universidade de Sao Paulo; BrasilFil: Brugières, Laurence. Institut de Cancerologie Gustave Roussy; FranciaFil: Else, Tobias. University of Michigan; Estados UnidosFil: Stoffel, Elena M.. University of Michigan; Estados UnidosFil: Maxwell, Kara N.. University of Pennsylvania; Estados UnidosFil: Achatz, Maria Isabel. Hospital Sirio-libanês; BrasilFil: Kowalski, Luis. A.c.camargo Cancer Center; BrasilFil: De Andrade, Kelvin C.. National Cancer Institute; Estados UnidosFil: Pappo, Alberto. St. Jude Children's Research Hospital; Estados UnidosFil: Letouze, Eric. Centre de Recherche Des Cordeliers; FranciaFil: Latronico, Ana Claudia. Universidade de Sao Paulo; BrasilFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Almeida, Madson Q.. Universidade de Sao Paulo; BrasilFil: Brondani, Vania B.. Universidade de Sao Paulo; BrasilFil: Bittar, Camila M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Emerson W.S.. Hospital Do Câncer de Cascavel; BrasilFil: Mathias, Carolina. Universidade Federal do Paraná; BrasilFil: Ramos, Cintia R.N.. Hospital de Câncer de Barretos; BrasilFil: Machado, Moara. National Cancer Institute; Estados UnidosFil: Zhou, Weiyin. National Cancer Institute; Estados UnidosFil: Jones, Kristine. National Cancer Institute; Estados UnidosFil: Vogt, Aurelie. National Cancer Institute; Estados UnidosFil: Klincha, Payal P.. National Cancer Institute; Estados UnidosFil: Santiago, Karina M.. A.c.camargo Cancer Center; BrasilFil: Komechen, Heloisa. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Paraizo, Mariana M.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Parise, Ivy Z.S.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Hamilton, Kayla V.. St. Jude Children's Research Hospital; Estados UnidosFil: Wang, Jinling. St. Jude Children's Research Hospital; Estados UnidosFil: Rampersaud, Evadnie. St. Jude Children's Research Hospital; Estados UnidosFil: Clay, Michael R.. St. Jude Children's Research Hospital; Estados UnidosFil: Murphy, Andrew J.. St. Jude Children's Research Hospital; Estados UnidosFil: Lalli, Enzo. Institut de Pharmacologie Moléculaire et Cellulaire; FranciaFil: Nichols, Kim E.. St. Jude Children's Research Hospital; Estados UnidosFil: Ribeiro, Raul C.. St. Jude Children's Research Hospital; Estados UnidosFil: Rodriguez-Galindo, Carlos. St. Jude Children's Research Hospital; Estados UnidosFil: Korbonits, Marta. Queen Mary University of London; Reino UnidoFil: Zhang, Jinghui. St. Jude Children's Research Hospital; Estados UnidosFil: Thomas, Mark G.. Colegio Universitario de Londres; Reino UnidoFil: Connelly, Jon P.. St. Jude Children's Research Hospital; Estados UnidosFil: Pruett-Miller, Shondra. St. Jude Children's Research Hospital; Estados UnidosFil: Diekmann, Yoan. Colegio Universitario de Londres; Reino UnidoFil: Neale, Geoffrey. St. Jude Children's Research Hospital; Estados UnidosFil: Wu, Gang. St. Jude Children's Research Hospital; Estados UnidosFil: Zambetti, Gerard P.. St. Jude Children's Research Hospital; Estados Unido

ACC/AHA/ASE 2003 Guideline Update for the Clinical Application of Echocardiography: Summary Article: A Report of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography)

"The previous guideline for the use of echocardiography was published in March 1997. Since that time, there have been significant advances in the technology of echocardiography and growth in its clinical use and in the scientific evidence leading to recommendations for its proper use. Each section has been reviewed and updated in evidence tables, and where appropriate, changes have been made in recommendations. A new section on the use of intraoperative transesophageal echocardiography (TEE) is being added to update the guidelines published by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists. There are extensive revisions, especially of the sections on ischemic heart disease; congestive heart failure, cardiomyopathy, and assessment of left ventricular (LV) function; and screening and echocardiography in the critically ill. There are new tables of evidence and extensive revisions in the ischemic heart disease evidence tables. Because of space limitations, only those sections and evidence tables with new recommendations will be printed in this summary article. Where there are minimal changes in a recommendation grouping, such as a change from Class IIa to Class I, only that change will be printed, not the entire set of recommendations. Advances for which the clinical applications are still being investigated, such as the use of myocardial contrast agents and three-dimensional echocardiography, will not be discussed.

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

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