Molecular-Based Immunohistochemical Algorithm for Uterine Leiomyosarcoma Diagnosis.

The morphologic assessment of uterine leiomyosarcoma (LMS) may be challenging, and diagnostic immunohistochemical (IHC) analysis is currently lacking. We evaluated the genomic landscape of 167 uterine LMS by targeted next-generation sequencing (NGS) to identify common genomic alterations. IHC analyses corresponding to these genomic landmarks were applied to a test cohort of 16 uterine LMS, 6 smooth muscle tumors of uncertain malignant potential (STUMP), and 6 leiomyomas with NGS data and a validation cohort of 8 uterine LMS, 12 STUMP, 21 leiomyomas and leiomyoma variants, 7 low-grade endometrial stromal sarcomas, and 2 diagnostically challenging uterine smooth muscle tumors. IHC results were individually interpreted by 3 pathologists blinded to NGS data. Overall, 94% of LMS showed ≥1 genomic alteration involving TP53, RB1, ATRX, PTEN, CDKN2A, or MDM2, with 80% showing alterations in ≥2 of these genes. In the test cohort, an initial panel of p53, Rb, PTEN, and ATRX was applied, followed by a panel of DAXX, MTAP, and MDM2 in cases without abnormalities. Abnormal p53, Rb, PTEN, and ATRX IHC expression was seen in 75%, 88%, 44%, and 38% of LMS, respectively, in the test cohort. Two or more abnormal IHC results among these markers were seen in 81% of LMS. STUMPs demonstrated only 1 IHC abnormality involving these markers. No IHC abnormalities were seen in leiomyomas. In the validation cohort, abnormal p53, Rb, and PTEN IHC results were seen in LMS, whereas rare STUMP or leiomyomas with bizarre nuclei showed IHC abnormalities involving only 1 of the markers. Abnormalities in ≥2 markers were present in both diagnostically challenging smooth muscle tumors, confirming LMS. Concordance was excellent among pathologists in the interpretation of IHC (κ = 0.97) and between IHC and NGS results (κ = 0.941). Uterine LMS exhibit genomic landmark alterations for which IHC surrogates exist, and a diagnostic algorithm involving molecular-based IHC may aid in the evaluation of unusual uterine smooth muscle tumors.

Interventions to increase the reporting of occupational diseases by physicians.

BACKGROUND: Under-reporting of occupational diseases is an important issue worldwide. The collection of reliable data is essential for public health officials to plan intervention programmes to prevent occupational diseases. Little is known about the effects of interventions for increasing the reporting of occupational diseases. OBJECTIVES: To evaluate the effects of interventions aimed at increasing the reporting of occupational diseases by physicians. SEARCH METHODS: We searched the Cochrane Occupational Safety and Health Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, OSH UPDATE, Database of Abstracts of Reviews of Effects (DARE), OpenSIGLE, and Health Evidence until January 2015.We also checked reference lists of relevant articles and contacted study authors to identify additional published, unpublished, and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs (cRCTs), controlled before-after (CBA) studies, and interrupted time series (ITS) of the effects of increasing the reporting of occupational diseases by physicians. The primary outcome was the reporting of occupational diseases measured as the number of physicians reporting or as the rate of reporting occupational diseases. DATA COLLECTION AND ANALYSIS: Pairs of authors independently assessed study eligibility and risk of bias and extracted data. We expressed intervention effects as risk ratios or rate ratios. We combined the results of similar studies in a meta-analysis. We assessed the overall quality of evidence for each combination of intervention and outcome using the GRADE approach. MAIN RESULTS: We included seven RCTs and five CBA studies. Six studies evaluated the effectiveness of educational materials alone, one study evaluated educational meetings, four studies evaluated a combination of the two, and one study evaluated a multifaceted educational campaign for increasing the reporting of occupational diseases by physicians. We judged all the included studies to have a high risk of bias.We did not find any studies evaluating the effectiveness of Internet-based interventions or interventions on procedures or techniques of reporting, or the use of financial incentives. Moreover, we did not find any studies evaluating large-scale interventions like the introduction of new laws, existing or new specific disease registries, newly established occupational health services, or surveillance systems. Educational materialsWe found moderate-quality evidence that the use of educational materials did not considerably increase the number of physicians reporting occupational diseases compared to no intervention (risk ratio of 1.11, 95% confidence interval (CI) 0.74 to 1.67). We also found moderate-quality evidence showing that sending a reminder message of a legal obligation to report increased the number of physicians reporting occupational diseases (risk ratio of 1.32, 95% CI 1.05 to 1.66) when compared to a reminder message about the benefits of reporting.We found low-quality evidence that the use of educational materials did not considerably increase the rate of reporting when compared to no intervention. Educational materials plus meetingsWe found moderate-quality evidence that the use of educational materials combined with meetings did not considerably increase the number of physicians reporting when compared to no intervention (risk ratio of 1.22, 95% CI 0.83 to 1.81).We found low-quality evidence that educational materials plus meetings did not considerably increase the rate of reporting when compared to no intervention (rate ratio of 0.77, 95% CI 0.42 to 1.41). Educational meetingsWe found very low-quality evidence showing that educational meetings increased the number of physicians reporting occupational diseases (risk ratio at baseline: 0.82, 95% CI 0.47 to 1.41 and at follow-up: 1.74, 95% CI 1.11 to 2.74) when compared to no intervention.We found very low-quality evidence that educational meetings did not considerably increase the rate of reporting occupational diseases when compared to no intervention (rate ratio at baseline: 1.57, 95% CI 1.22 to 2.02 and at follow-up: 1.92, 95% CI 1.48 to 2.47). Educational campaignWe found very low-quality evidence showing that the use of an educational campaign increased the number of physicians reporting occupational diseases when compared to no intervention (risk ratio at baseline: 0.53, 95% CI 0.19 to 1.50 and at follow-up: 11.59, 95% CI 5.97 to 22.49). AUTHORS' CONCLUSIONS: We found 12 studies to include in this review. They provide evidence ranging from very low to moderate quality showing that educational materials, educational meetings, or a combination of the two do not considerably increase the reporting of occupational diseases. The use of a reminder message on the legal obligation to report might provide some positive results. We need high-quality RCTs to corroborate these findings.Future studies should investigate the effects of large-scale interventions like legislation, existing or new disease-specific registries, newly established occupational health services, or surveillance systems. When randomisation or the identification of a control group is impractical, these large-scale interventions should be evaluated using an interrupted time-series design.We also need studies assessing online reporting and interventions aimed at simplifying procedures or techniques of reporting and the use of financial incentives.

The impact of allergic rhinitis on the management of asthma in a working population.

BACKGROUND: Currently, little data is available about the management of asthma in the working population. The aim of this study was to describe asthma control and severity among workers according to current or previous allergic rhinitis comorbidity. METHODS: A network of occupational physicians participated in this pilot study on a voluntary basis. They included a random sample of salaried workers during their systematic occupational medical check-up. All subjects completed a self-administered questionnaire based on the European Community Respiratory Health Survey screening questionnaire, and if they reported any respiratory symptoms including allergic rhinitis, the physician filled in a medical questionnaire. Current asthma control and severity were evaluated according to 2006 Global Initiative for Asthma guidelines. RESULTS: A total of 110 occupational physicians from two French regions participated. Out of the 6906 employees screened, 3102 identified respiratory symptoms and completed the medical questionnaire and performed spirometry. Overall, 374 were identified as current asthmatics, including 271 (72.5%) with allergic rhinitis. Among current asthmatics with current allergic rhinitis (n = 95), 68.8% had partially controlled asthma or uncontrolled asthma, including 51.6% who received insufficient anti-asthmatic treatment. Partly or no control asthma was not associated with current rhinitis (OR = 1.4; 95% CI: 0.8-2.7). Current asthmatics with current or previous allergic rhinitis had a significantly lower risk of emergency department visits than current asthmatics without allergic rhinitis (respectively 11.6, 17.1 and 29.1%; P = 0.002). CONCLUSIONS: Most current asthmatics both with and without allergic rhinitis had uncontrolled asthma, with inappropriate treatment. Future intervention strategies need to be developed for effective control and prevention of asthma in the workplace.

Underreporting of musculoskeletal disorders in 10 regions in France in 2009.

BACKGROUND: Underreporting of occupational diseases (OD) has been quantified, in particular in the United States, but little information is available in other countries. The aim of this study was to evaluate underreporting of musculoskeletal disorders (MSD) in France in 2009. METHODS: We calculated an indicator that approximated the underreporting rate of MSD in 10 regions of France. Two databases were used: data on OD compensated by insurance funding and data from the surveillance program for uncompensated work-related diseases. Analyses were performed for carpal tunnel syndrome (CTS) and elbow, shoulder, and lumbar spine MSD. RESULTS: The underreporting rate was estimated at 59% (range 52-64%) for CTS, 73% (range 67-79%) for elbow MSD, 69% (range 63-74%) for shoulder MSD, and 63% (range 50-76%) for lumbar spine MSD. CONCLUSIONS: This study revealed that MSD are substantially underreported in France, as in the United States, despite the differences in workers' compensation systems.

Psychosocial risk factors for depressive symptoms after the AZF chemical factory explosion in Toulouse, France.

BACKGROUND: On 21 September 2001, a huge explosion occurred in a chemical plant in Toulouse. The hypothesis of the study was that the level of depressive symptoms after an industrial disaster would be related to the intensity of exposure and the characteristics of the exposed population, as well as to the consequences of the disaster during the following months. METHODS: A random sample of the population living close to the plant at the time of the explosion was included in a cross-sectional study, and 811 persons aged > 18 years were interviewed at home. The depressive symptoms score was analysed by gender in relation to characteristics of the population before the explosion, immediate exposure to the explosion and post-trauma factors. RESULTS: The mean depressive symptoms scores (± SD) 18 months after the explosion were 17.8 (± 1) in women and 13.5 (± 1) in men. Age > 45 years and psychiatric treatment in the previous year; high immediate exposure (proximity to the site at the time of the explosion < 2500 m); and post-trauma factors such as financial difficulties or physical sequelae during the months after the disaster were related to a higher depressive symptoms score in both men and women. CONCLUSION: In the population living near the site of an industrial explosion, individual vulnerability, exposure and post-trauma factors were associated with depressive symptoms. All three sets of factors need to be taken into account when planning a response to a disaster and reducing the psychological aftermath.

Environmental pollutant hexachlorobenzene induces hypertension in a rat model.

Hexachlorobenzene (HCB) is a dioxin-like environmental pollutant, widely distributed in the environment. New research links exposure to high levels of persistent organic environmental toxicants to cardiovascular disease, however little is known about the effect of HCB on vascular function and on blood pressure. The purpose of the present study was to evaluate biochemical and cardiovascular changes resulting from subchronic HCB exposure. Adult female Sprague-Dawley rats were treated with vehicle or HCB (5 or 500 mg/kg b.w) for 45 days. Systolic blood pressure (BP), recorded by tail cuff plethysmography, was significantly increased at 35, 40 and 45 days of 500 mg/kg HCB-treatment. HCB (500 mg/kg) increased arterial thickness, while both 5 and 500 mg/kg HCB decreased proliferating cell nuclear antigen (PCNA) protein levels and cellular nuclei in abdominal aortas indicating a hypertrophic process. Also, aortas from both groups of HCB-treated rats presented higher sensitivity to noradrenalin (NA) and a significant decrease in maximum contractile response. Arteries from 500 mg/kg HCB-treated rats showed a significant increase in the levels of transforming growth factor-ß1 (TGF-ß1) mRNA and angiotensin II type1 receptor (AT1), and a significant decrease in estrogen receptor alpha (ERα), endothelial nitric oxidide synthase (eNOS) protein expression and deiodinase II (DII) mRNA levels. In conclusion, we have demonstrated for the first time that subchronic HCB administration significantly increases BP and alters associated cardiovascular parameters in rats. In addition, HCB alters the expression of key vascular tissue molecules involved in BP regulation, such as TGF-ß1, AT1, ERα, eNOS and DII.

Short term effects of air pollution on hospitalizations for cardiovascular diseases in eight French cities: the PSAS program.

INTRODUCTION: Short term associations between air pollution indicators and hospitalizations for cardiovascular diseases have been suggested by epidemiological and clinical studies. The present study aims at estimating the association between particles with diameter <10 microm (PM(10)), nitrogen dioxide (NO(2)) and ozone and hospitalizations for cardiovascular diseases in eight French cities during the 1998-2003 period. METHODS: The daily number of hospitalizations in each city was extracted from the French hospital information system (PMSI) for cardiovascular diseases, cardiac diseases, ischemic heart diseases and stroke. Excess relative risks (ERRs) of hospitalization associated with a 10 microg/m(3) increase in pollutant levels were estimated in each city by fitting a Poisson regression model, controlling for well-known confounding factors and temporal trends. City-specific results were then combined by inverse variance weighting. RESULTS: Daily number of hospitalizations for cardiovascular diseases was associated with PM(10) levels (for a 10 microg/m(3) increase, ERR=0.8%, 95% CI: [0.2, 1.5]), with NO(2) (1.1%, [0.6, 1.6]) but not with ozone (0.1% [-0.2%, 0.5%]). Associations were stronger in people aged 65 years and over, and when only hospitalizations for ischemic heart diseases were considered. No association was found between strokes and air pollution levels. DISCUSSION: Our study suggests that the ambient levels of air pollutants currently experienced in the eight French cities, which are close to European air quality guidelines, are yet linked to a short term increase of hospitalizations for cardiovascular diseases. These results are consistent with epidemiological and toxicological data on the cardiovascular effects of air pollution.

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration.

The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.

Paraoxonase 1 gene polymorphisms and enzyme activities in coronary artery disease and its relationship to serum lipids and glycemia.

OBJECTIVES: Oxidative stress and inflammation are important processes in development of atherosclerosis. Paraoxonase 1 (PON1) is a bioscavenger enzyme associated with inflammation and oxidative stress. We evaluate the association of two single nucleotide polymorphisms in PON1 gene, and enzyme activities with lipid profile and glycemia. METHODS: This case-control study consisted of 126 patients with coronary artery disease (CAD) and 203 healthy controls. PON Q192R and L55M polymorphisms were detected by real-time PCR. Paraoxonase and arylesterase activities were determined spectrophotometrically. Blood glucose, cholesterol, triglycerides, HDL, and LDL were measured. RESULTS: PON1 QR192 polymorphism had a major effect on paraoxonase but no effect on arylesterase serum activities. Paraoxonase activity was higher in RR genotype and lowest in QQ genotype. Paraoxonase and arylesterase activities were higher in LL and lower in MM genotypes of PON1 LM55 polymorphism. RQ and LM variants showed intermediate activities between respective homozygous. Elevated concentrations of triglycerides in cases correlate with QQ variant or the presence of M allele. Glucose levels were elevated in cases with QQ variant or with the presence of M allele. Cholesterol and LDL did not show variations in control and cases with any variant of both polymorphisms. HDL is lower in cases with respect to controls independently of genotypes. All differences were significant with p<0.05. CONCLUSIONS: Our results confirm the relationship between variations in PON1 activities and lipid metabolism, and showed that genetically programmed low PON1 activities would have certain responsibility in the increase in glycemia and concomitantly the aggravation of atherosclerotic disease.

Metabolic Changes Following Perinatal Asphyxia: Role of Astrocytes and Their Interaction with Neurons.

Perinatal Asphyxia (PA) represents an important cause of severe neurological deficits including delayed mental and motor development, epilepsy, major cognitive deficits and blindness. The interaction between neurons, astrocytes and endothelial cells plays a central role coupling energy supply with changes in neuronal activity. Traditionally, experimental research focused on neurons, whereas astrocytes have been more related to the damage mechanisms of PA. Astrocytes carry out a number of functions that are critical to normal nervous system function, including uptake of neurotransmitters, regulation of pH and ion concentrations, and metabolic support for neurons. In this work, we aim to review metabolic neuron-astrocyte interactions with the purpose of encourage further research in this area in the context of PA, which is highly complex and its mechanisms and pathways have not been fully elucidated to this day.

Long lasting cerebellar alterations after perinatal asphyxia in rats.

The developing brain may be particularly vulnerable to injury before, at and after birth. Among possible insults, hypoxia suffered as a consequence of perinatal asphyxia (PA) exhibits the highest incidence levels and the cerebellar circuitry appears to be particularly susceptible, as the cellular makeup and the quantity of inputs change quickly during days and weeks following birth. In this work, we have used a murine model to induce severe global PA in rats at the time of birth. Short-term cerebellar alterations within this PA model have been previously reported but whether such alterations remain in adulthood has not been conclusively determined yet. For this reason, and given the crucial cerebellar role in determining connectivity patterns in the brain, the aim of our work is to unveil long-term cerebellum histomorphology following a PA insult. Morphological and cytological neuronal changes and glial reaction in the cerebellar cortex were analyzed at postnatal 120 (P120) following injury performed at birth. As compared to control, PA animals exhibited: (1) an increase in molecular and granular thickness, both presenting lower cellular density; (2) a disarrayed Purkinje cell layer presenting a higher number of anomalous calbindin-stained cells. (3) focal swelling and marked fragmentation of microtubule-associated protein 2 (MAP-2) in Purkinje cell dendrites and, (4) an increase in glial fibrillary acidic protein (GFAP) expression in Bergmann cells and the granular layer. In conclusion, we demonstrate that PA produces long-term damage in cellular histomorphology in rat cerebellar cortex which could be involved in the pathogenesis of cognitive deficits observed in both animals and humans.

Comparison of homocysteinemia and MTHFR 677CT polymorphism with Framingham Coronary Heart Risk Score.

OBJECTIVE: The Framingham Coronary Heart Disease Risk Score is an important clinical tool. The aim of this cross-sectional study was to compare plasma homocysteine levels and polymorphism 677CT MTHFR with this score to determine the utility of these new biomarkers in clinical practice. METHODS: Plasma homocysteine levels determined by chemiluminescence and polymorphism 677CT MTHFR, detected by PCR-RFLP, were compared with Framingham coronary risk score in a cross-sectional survey on 68 men and 165 women. RESULTS: Coronary heart disease risk augmented with an increase in the quartile of plasma homocysteine. In the 2nd, 3rd and 4th quartile of plasma homocysteine, men showed significantly (P<0.001) higher risk than women. For the highest quartile of plasma homocysteine, OR of high-risk (10-year risk≥20%) compared with the lowest quartile was 17.45 (95% CI: 5.79-52.01). Frequencies of CT and TT genotype and T allele were not over-represented in the individuals with score≥10%. The higher plasma homocysteine concentrations in individuals with score≥10% with respect to those with low risk (P<0.005 and P<0.001) were not due to the presence of T allele. The T allele (CT+TT genotypes) of the MTHFR C677T polymorphism was not significantly associated with an increased risk of coronary disease (OR=1.09, 95% CI=0.50-2.39, P=0.844). CONCLUSIONS: The present study demonstrated an association between plasma homocysteine levels and the severity of coronary heart disease estimated with the Framingham coronary risk score, and this association appeared to be independent on the genotype of MTHFR. We postulate that plasma homocysteine is effective enough, considered even in isolation.

Paraoxonase 1 gene polymorphisms and enzyme activities in coronary artery disease and its relationship to serum lipids and glycemia / Polimorfismos en el gen de la paraoxonasa 1 y sus actividades enzimáticas en la enfermedad coronaria. Su relación con el perfil lipídico y la glucemia

Abstract Objectives Oxidative stress and inflammation are important processes in development of atherosclerosis. Paraoxonase 1 (PON1) is a bioscavenger enzyme associated with inflammation and oxidative stress. We evaluate the association of two single nucleotide polymorphisms in PON1 gene, and enzyme activities with lipid profile and glycemia. Methods This case-control study consisted of 126 patients with coronary artery disease (CAD) and 203 healthy controls. PON Q192R and L55M polymorphisms were detected by real-time PCR. Paraoxonase and arylesterase activities were determined spectrophotometrically. Blood glucose, cholesterol, triglycerides, HDL, and LDL were measured. Results PON1 QR192 polymorphism had a major effect on paraoxonase but no effect on arylesterase serum activities. Paraoxonase activity was higher in RR genotype and lowest in QQ genotype. Paraoxonase and arylesterase activities were higher in LL and lower in MM genotypes of PON1 LM55 polymorphism. RQ and LM variants showed intermediate activities between respective homozygous. Elevated concentrations of triglycerides in cases correlate with QQ variant or the presence of M allele. Glucose levels were elevated in cases with QQ variant or with the presence of M allele. Cholesterol and LDL did not show variations in control and cases with any variant of both polymorphisms. HDL is lower in cases with respect to controls independently of genotypes. All differences were significant with p < 0.05. Conclusions Our results confirm the relationship between variations in PON1 activities and lipid metabolism, and showed that genetically programmed low PON1 activities would have certain responsibility in the increase in glycemia and concomitantly the aggravation of atherosclerotic disease.

Resumen Objetivos La enzima paraoxonasa 1 (PON1), está asociada con el estrés oxidativo y la inflamación, procesos importantes en el desarrollo de la aterosclerosis. Evaluamos la asociación de 2 polimorfismos de un solo nucleótido en el gen PON1 y sus actividades enzimáticas con el perfil lipídico y la glucemia. Métodos Estudio caso-control en 126 pacientes con enfermedad coronaria y 203 controles sanos. Los polimorfismos PON Q192R y L55M fueron detectados por PCR en tiempo real y las actividades de paraoxonasa y arilesterasa por espectrofotometría. Se midieron glucemia, colesterol, triglicéridos, HDL y LDL. Resultados El polimorfismo PON1 QR192 afectó la actividad de paraoxonasa pero no la de arilesterasa. La actividad de paraoxonasa fue mayor en el genotipo RR y menor en QQ. Ambas actividades fueron mayores en el genotipo LL y menores en MM del polimorfismo PON1 LM55. Las variantes RQ y LM mostraron actividades intermedias entre los respectivos homocigotos. Concentraciones elevadas de triglicéridos en los casos correlacionaron con la variante QQ o la presencia del alelo M. Los niveles de glucosa fueron elevados en los casos QQ o con la presencia del alelo M. El colesterol y el LDL no variaron ni en los casos ni en los controles con ambos polimorfismos. El HDL fue menor en los casos respecto de los controles, independientemente del genotipo. Conclusiones Los resultados confirman la relación entre las variaciones en las actividades de PON1 y el metabolismo lipídico y mostraron que las bajas actividades de PON1 genéticamente programadas tendrían cierta responsabilidad en el aumento de la glucemia y, concomitantemente, en la agravación de la enfermedad aterosclerótica.

Comparison of homocysteinemia and MTHFR 677CT polymorphism with Framingham Coronary Heart Risk Score / Comparación de homocisteinemia y polimorfismo 677CT MTHFR con el Escore Framingham de Riesgo Coronario

Objective: The Framingham Coronary Heart Disease Risk Score is an important clinical tool. The aim of this cross-sectional study was to compare plasma homocysteine levels and polymorphism 677CT MTHFR with this score to determine the utility of these new biomarkers in clinical practice. Methods: Plasma homocysteine levels determined by chemiluminescence and polymorphism 677CT MTHFR, detected by PCR-RFLP, were compared with Framingham coronary risk score in a cross-sectional survey on 68 men and 165 women. Results: Coronary heart disease risk augmented with an increase in the quartile of plasma homocysteine. In the 2nd, 3rd and 4th quartile of plasma homocysteine, men showed significantly (P < 0.001) higher risk than women. For the highest quartile of plasma homocysteine, OR of high-risk (10-year risk ≥ 20%) compared with the lowest quartile was 17.45 (95% CI: 5.79-52.01). Frequencies of CT and TT genotype and T allele were not over-represented in the individuals with score ≥ 10%. The higher plasma homocysteine concentrations in individuals with score ≥ 10% with respect to those with low risk (P < 0.005 and P < 0.001) were not due to the presence of T allele. The T allele (CT + TT genotypes) of the MTHFR C677T polymorphism was not significantly associated with an increased risk of coronary disease (OR = 1.09, 95% CI = 0.50-2.39, P = 0.844). Conclusions: The present study demonstrated an association between plasma homocysteine levels and the severity of coronary heart disease estimated with the Framingham coronary risk score, and this association appeared to be independent on the genotype of MTHFR. We postulate that plasma homocysteine is effective enough, considered even in isolation.

Objetivo: La puntuación del riesgo coronario de Framingham es una importante herramienta clínica. El objetivo del presente estudio transversal fue comparar los niveles plasmáticos de homocisteína plasmática y el polimorfismo 677CT de la MTHFR con esta herramienta para determinar la utilidad de estos nuevos biomarcadores en la práctica clínica. Métodos: Los niveles de homocisteína plasmática determinados por quimioluminiscencia y el polimorfismo 677CT MTHFR por PCR-RFLP fueron comparados con la puntuación del riesgo coronario de Framingham en un estudio transversal sobre 68 hombres y 165 mujeres. Resultados: El riesgo de enfermedad coronaria aumentó con el incremento en los cuartiles de homocisteína plasmática. En el segundo, tercero y cuarto cuartil de homocisteína plasmática los hombres mostraron significativamente (p < 0.001) mayor riesgo que las mujeres. Para el cuartil más alto de homocisteína plasmática, la OR de riesgo alto (riesgo a 10 años ≥ 20%) comparado con el cuartil más bajo fue 17,45 (IC 95%: 5,79-52,01; p < 0.001). Las frecuencias de los genotipos CT y TT y del alelo T no estuvieron aumentados en los individuos con una puntuación ≥ 10%. Las mayores concentraciones de homocisteína plasmática en los individuos con una puntuación ≥ 10% respecto a los de bajo riesgo (p < 0.005 y p < 0.001) no se debieron a la presencia del alelo T. El alelo T (genotipos CT + TT) del polimorfismo MTHFR C677T no estuvo significativamente asociado con mayor riesgo de enfermedad coronaria (OR = 1.09, IC 95% = 0.50-2.39, p = 0.844). Conclusiones: El presente estudio mostró una asociación entre los niveles de homocisteína plasmática y la severidad de la enfermedad coronaria estimada con el algoritmo de puntuación de riesgo coronario de Framingham y esta asociación resultó ser independiente del genotipo de MTHFR. Postulamos que la homocisteína plasmática es lo suficientemente eficaz, estudiada incluso aisladamente.

Hearing status after an industrial explosion: experience of the AZF explosion, 21 September 2001, France.

OBJECTIVES: Following the explosion of a chemical plant in France, a study was conducted to analyse the relationship between hearing thresholds and distance from the explosion based on post- and pre-blast audiometric data, and to describe the functional symptoms and visits for hearing problems. METHODS: Audiometric tests with standard procedure of 511 workers of a company located near the explosion were proposed and conducted by the occupational medicine department after the explosion. Past occupational noise exposure, past medical history of ear problems, distance from the explosion, functional symptoms and visits for hearing problems following explosion and results of past audiometric tests if available were collected. Workers were classified as "exposed" or "less exposed" according to the distance from the explosion. Mean decibel threshold shifts for each ear were analysed by frequency with Student's t test and by multiple linear regression taking into account confounding factors. RESULTS: Of a total of 425 (83%) of the firm's workers who participated in the study, 49% had received an audiometric test before the explosion. Hearing shift between pre- and post-explosion audiograms was significantly greater for the "exposed" group than for the "less exposed" one at 2,000 and 4,000 Hz (P < 0.05, P < 0.001, respectively) and borderline at 6,000 Hz (P = 0.09) for the right ear and at 2,000 (P < 0.01), 6,000 and 8,000 Hz (P < 0.05) for the left ear. Among those of the "exposed" workers who reported any functional symptom following the explosion, 45% did not visit an ENT specialist despite these signs. CONCLUSIONS: The study demonstrated statistically significant hearing shift from 2,000 to 6,000 Hz in relation with distance from the explosion and showed that even when functional symptoms were present, people did not necessarily seek medical advice. Screening for hearing loss should be recommended for people most exposed to excess acoustic pressure, in order to offer them prevention advice.

Cognitive function and caregiver burden: predictive factors for eating behaviour disorders in Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) commonly develop aversive feeding behaviours. These behaviours lead to weight loss and frequently to physicians using tube feeding. Little is known about factors correlated with feeding difficulties during AD. OBJECTIVE: To investigate predictors of aversive feeding behaviours (AFBs) which occurred during a one-year interval among AD patients living at home with a caregiver. METHOD: One-year study initiated in January 1998 with 224 AD patients and their caregivers. MAIN OUTCOME MEASURES: all patients underwent a nutritional, psychologic and functional evaluation at baseline and one year later. Feeding difficulties were assessed using the Feeding Dependency Scale and the Aversive Feeding Behaviour Inventory. The Burden Interview was also done to assess the material and emotional burden. RESULTS: Initial feeding difficulties were significantly associated with the age of the caregiver, the severity of the disease and the initial patient's autonomy and psychological functioning (mood and behaviour disorders). AD patients, who lived with a more affected caregiver at baseline, developed feeding difficulties and AFBs during the follow-up. Logistic regression analysis showed a positive association between AFBs worsening and the initial caregiver's burden after controlling for confounding factors. On the other hand, memory impairment was inversely associated with AFBs. CONCLUSIONS: Both cognitive impairment and family stress can help in predicting which AD patients living at home will develop AFBs. Nutritional information and support to families are probably the best strategies to prevent AFBs during AD and to improve consequently the patient's and caregiver's quality of life.