Epigenetic regulation of ID4 in the determination of the BRCAness phenotype in breast cancer.

BRCAness breast tumors represent a group of sporadic tumors characterized by a reduction in BRCA1 gene expression. As BRCA1 is involved in double-strand breaks (DSBs) repair, dysfunctional BRCA pathway could make a tumor sensitive to DNA damaging drugs (e.g., platinum agents). Thus, accurately identifying BRCAness could contribute to therapeutic decision making in patients harboring these tumors. The purpose of this study was to identify if BRCAness tumors present a characteristic methylation profile and/or were related to specific clinico-pathological features. BRCAness was measured by MLPA in 63 breast tumors; methylation status of 98 CpG sites within 84 cancer-related genes was analyzed by MS-MLPA. Protein and mRNA expressions of the selected genes were measured by quantitative real-time PCR and Western Blot. BRCAness was associated with younger age, higher nuclear pleomorphism, and triple-negative (TN) status. Epigenetically, we found that the strongest predictors for BRCAness tumors were the methylations of MLH1 and PAX5 plus the unmethylations of CCND2 and ID4. We determined that ID4 unmethylation correlated with the expression levels of both its mRNA and protein. We observed an inverse relation between the expressions of ID4 and BRCA1. To the best of our knowledge, this is the first report suggesting an epigenetic regulation of ID4 in BRCAness tumors. Our findings give new information of BRCAness etiology and encourage future studies on potential drug targets for BRCAness breast tumors.

[Gender differences in the use of tumour markers]. / Diferencias de género en el uso de marcadores tumorales.

INTRODUCTION AND OBJECTIVE: Gender is one of the factors that can influence the use of health resources. The use of tumour markers is widespread, due to the importance of these in monitoring cancer development. The aim of this study is to analyse the influence of gender on the use of tumour markers, and to investigate whether there are differences in their use. MATERIAL AND METHODS: A longitudinal, retrospective and descriptive study, with a 2-year follow-up, was conducted in the catchment area of the University Hospital of Padua. An analysis was performed on 23,059 analytical requests for tumour markers. A descriptive and frequency analysis was performed on all variables. The statistical analysis was performed using Chi squared, Student t and Mann-Whitney U to test for significance. RESULTS: The number of requests for women (1.5) was lower than men (1.6). In patients with tumour pathology, the number of requests was higher than in patients without tumour disease. In the analysis by disease and gender, the difference remained significant. As regards the number of tumour markers per request, the difference between genders was also significant: 2.13 in males versus 2.85 in women. Similar results were obtained when requests for tumour markers linked to gender-related diseases were eliminated. CONCLUSIONS: There are differences in the use of tumour markers by gender with the number of requests for male patients being higher than for females. However, the number of tumour markers per request is greater in women than in men.

Epigenetic alterations in a gastric leiomyoma.

Leiomyomas constitute 2.5% of all resected neoplasms of the stomach. They are usually asymptomatic, but may present mucosal ulceration. Aberrant DNA methylation is a well-defined epigenetic change in human neoplasms; however, gene-acquired methylation may not necessarily be related with a malignant phenotype. In this report we analyzed in a gastric leiomyoma, the methylation status of 84 CpGI in tumor suppressor and DNA repair genes. We analyzed the tumor center (TC) and tumor periphery (TP) separately. We found aberrant methylation in 2/84 CpGI in the TC portion, that is, MLH1 and MSH3, and 5/84 CpGI in the TP, that is, MLH1, MSH3, APC, MSH6, and MGMT. The gene with the highest methylation percentage in the TC and TP was MLH1. Given that MLH1 methylation has been associated with microsatellite instability, we analyzed the status of the microsatellite Bat-26. We found that neither the TC nor the TP presented instability. The methylation of MLH1, MGMT, and APC has been described in GISTs, but to the best of our knowledge this is the first time that the methylation of these genes has been associated with gastric leiomyoma. Further research should be conducted to identify reliable molecular markers that could differentiate between GISTs and gastric leiomyomas.

Cuestionario ISMP-España y estrategia de mejora en el uso seguro del medicamento dentro del Servicio Andaluz de Salud / ISMP-Spain questionnaire and strategy for improving good medication practices in the andalusian health system

Objetivo: Describir la estrategia seguida en los hospitales del Servicio Andaluz de Salud para potenciar el uso seguro del medicamento utilizando como herramienta base el cuestionario de autoevaluación de la seguridad del sistema de utilización de los medicamentos en los hospitales, adaptado por el Instituto para el Uso Seguro de los Medicamentos en España. Material y métodos La estrategia se desarrolló en varias fases. Un análisis del informe de evaluación de la seguridad del sistema de utilización de los medicamentos en los hospitales públicos de Andalucía publicado por el ministerio de Sanidad y Consumo en 2008 seguido del establecimiento de un diagnóstico de partida del grado de seguridad en el uso de los medicamentos en los hospitales andaluces y priorización de las áreas de mejora. El desarrollo de un catálogo de buenas prácticas disponibles en el entorno web del observatorio para la seguridad del paciente de la agencia de calidad sanitaria andaluza, difusión de la estrategia a través de talleres formativos y la puesta en marcha de un sistema de evaluación del grado de cumplimiento de cada una de las buenas prácticas dirigido a hospitales a partir del cual componer un mapa de centros de referencia, completan las actuaciones realizadas. Resultados Se detectaron áreas de mejora en varios de los criterios esenciales del cuestionario. Estas áreas de mejora se relacionaron con procesos habituales que sigue el medicamento en la práctica clínica habitual. Así, se elaboraron 7 guías de buena práctica que recogen de forma transversal todos los elementos de evaluación del cuestionario relacionados con el proceso clínico a mejorar. Conclusiones El cuestionario de autoevaluación adaptado por ISMP-España constituye una buena herramienta para diseñar una intervención sistemática y racional en el uso seguro del medicamento dirigida a un grupo de hospitales que comparten los mismos valores (AU)

Objective: To describe the strategy employed by Andalusian public health service hospitals to foster safe medication use. The self-evaluation questionnaire on drug system safety in hospitals, adapted by the Spanish Institute for Safe Medication Practices was used as a fundamental tool to that end. Material and method: The strategy is developed in several phases. We analyse the report evaluating drug system safety in Andalusian public hospitals published by the Spanish Ministry of Health and Consumption in 2008 and establish a grading system to assess safe medication practices in Andalusian hospitals and prioritise areas needing improvement. We developed a catalogue of best practices available in the web environment belonging to the Andalusian health care quality agency’s patient safety observatory. We publicised the strategy through training seminars and implemented a system allowing hospitals to evaluate the degree of compliance for each of the best practices, and based on that system, we were able to draw up a map of centres of reference. Results: We found areas for improvement among several of the questionnaire’s fundamental criteria. These areas for improvement were related to normal medication procedures in daily clinical practice. We therefore wrote 7 best practice guides that provide a cross-section of the assessment components of the questionnaire related to the clinical process needing improvement. Conclusions: The self-evaluation questionnaire adapted by ISMP-Spain is a good tool for designing a systematic, rational intervention to promote safe medication practices and intended for a group of hospitals that share the same values (AU)

[ISMP-Spain questionnaire and strategy for improving good medication practices in the Andalusian health system]. / Cuestionario ISMP-España y estrategia de mejora en el uso seguro del medicamento dentro del Servicio Andaluz de Salud.

OBJECTIVE: To describe the strategy employed by Andalusian public health service hospitals to foster safe medication use. The self-evaluation questionnaire on drug system safety in hospitals, adapted by the Spanish Institute for Safe Medication Practices was used as a fundamental tool to that end. MATERIAL AND METHOD: The strategy is developed in several phases. We analyse the report evaluating drug system safety in Andalusian public hospitals published by the Spanish Ministry of Health and Consumption in 2008 and establish a grading system to assess safe medication practices in Andalusian hospitals and prioritise areas needing improvement. We developed a catalogue of best practices available in the web environment belonging to the Andalusian health care quality agency's patient safety observatory. We publicised the strategy through training seminars and implemented a system allowing hospitals to evaluate the degree of compliance for each of the best practices, and based on that system, we were able to draw up a map of centres of reference. RESULTS: We found areas for improvement among several of the questionnaire's fundamental criteria. These areas for improvement were related to normal medication procedures in daily clinical practice. We therefore wrote 7 best practice guides that provide a cross-section of the assessment components of the questionnaire related to the clinical process needing improvement. CONCLUSIONS: The self-evaluation questionnaire adapted by ISMP-Spain is a good tool for designing a systematic, rational intervention to promote safe medication practices and intended for a group of hospitals that share the same values.

Utilidad de los sistemas analíticos a la cabecera del enfermo en condiciones emergentes y con accesibilidad limitada / Utility of the Point-of-Care-Testing devices in emergent conditions and with limited accessibility

Introducción: La seguridad del paciente es uno de los objetivos principales de todo sistema sanitario. El Hospital de Ronda atiende a más de 120.000 habitantes. Da cobertura a seis áreas básicas de salud, en total treinta y un puntos de atención médica. La Comarca de la Serranía de Ronda es un entorno rural montañoso. Presenta una amplia dispersión geográfica y comunicaciones difíciles por carretera. El tiempo medio de acceso al hospital de Ronda es de 60 minutos. El perfil poblacional de la comarca es característico de una zona rural. Metodología: El análisis sobre seguridad del paciente constató que la dispersión geográfica y la dificultad de acceder al hospital eran problemas prioritarios. Se proporcionó a los equipos móviles urgentes de sistemas analíticos portátiles (i-STAT, Abbott) capaces de realizar analíticas rápidas y fiables a la cabecera del enfermo. Resultados y conclusiones: Los profesionales han valorado muy positivamente esta medida al poder resolver mayor número de asistencias sin tener que trasladar al paciente (AU)

Introduction: Patient safety is one of the main objectives in our health system for the continuous improvement of quality of care and the promotion of clinical excellence. The Ronda Hospital covers a population of more than 120,000 inhabitants in two different provinces, being split into six Basic Health Areas with their corresponding health centres plus three associated Medical Centres, making thirty one points of care that have to be staffed. The rural area of Serranía de Ronda, due to being mountainous, is geographically complicated. It is widely dispersed and communication it has a difficult transportation due to be carried out by secondary roads, which are even worse during winter. The average travelling times to Ronda Hospital, which is the only hospital in the region, is around 60 minutes. The population profile of the Rural Area is characteristic of an ageing population. Methodology: An analysis of Patient Safety showed the geographical dispersion and difficulty to get to hospital was detected as priority problems and those which had most influence on patient safety. Ten dry chemical analysers (i-STAT, Abbott) have been installed in the ambulances which attend the reference population. Results and Conclusions: The professionals positively value the availability of another diagnostic tool, as well as having had a response to their demands to the referred patient safety (AU)

Bone mineral density in women with ankylosing spondylitis.

OBJECTIVE: To determine bone mineral density (BMD) in premenopausal women with early ankylosing spondylitis (AS). METHODS: Eighteen premenopausal women with AS without syndesmophytes, interapophysiary arthritis, and/or coxofemoral joint destruction were studied. BMD was analyzed at lumbar spine and femoral neck by dual energy x-ray absorptiometry (Hologic QDR 1000). Z scores and T scores related to the general Spanish population were recorded. Comparisons were performed using the Student t test. Pearson's correlation coefficients were used to study the correlation between BMD and the variables. Following the WHO classification, osteopenia was diagnosed in patients with T score between -1 and -2.5 and osteoporosis in those with T score < -2.5 at lumbar spine or femoral neck. RESULTS: The mean Z score for spine BMD was -0.19+/-0.7, and -0.03+/-0.85 for femoral neck BMD. There were no significant differences of Z score values compared to the general population. No significant correlation was found between BMD and disease duration, radiology sacroiliac score, and spine mobility. Densitometry showed osteopenia in 2 patients and osteoporosis in none. CONCLUSION: We found a slight reduction in BMD in premenopausal women with early AS, but the difference was not statistically significant. We discuss the factors related to its pathogenesis.

[Water fluoridation in the Region of Murcia]. / La fluoración de aguas en la Región de Murcia.

BACKGROUND: The purpose of this study is that of expounding upon the natural fluoride ion concentrations in the public water supplies of all of the municipalities in the Region of Murcia in 1991, in addition to the trend in said concentrations throughout the 1992-1996 period, this being a time during which fluoride was added to the water supply as a public health measure. METHODS: The methods employed for the findings were those of potentiometer-based gauging by means of standard addition and direct findings using a potentiometer equipped with an ion-selective electrode. RESULTS: The findings indicate that major fluctuations have taken place in the amounts of fluoride in these waters throughout the initial years during which fluoride was added to the water supply, without it being possible to establish broad-scope geographical patterns, to later tend toward stabilization during the final years of the time period in question, in which solely the municipalities supplied by the Letur treatment plant (which supplies the central and northwestern areas of the Region) showed levels nearing 0.8 mg/l, been maintained, which are those stipulated under the regulations resolving in favor of the addition of fluoride. CONCLUSIONS: We can conclude that only a portion of the municipalities of the Murcia Region has reached the optimum value for the concentration of fluoride in drinking water proposed by the Autonomous Community (0.8 mg/liter), or values close to it (0.6-0.7 mg/liter) during the period studied.

Tertiary hyperparathyroidism after long-term phosphate supplementation in adult-onset hypophosphataemic osteomalacia.

We report the development of tertiary hyperparathyrodism in a patient with a sporadic form of adult-onset hypophosphataemic osteomalacia who had been treated with vitamin D or calcitriol and large doses of phosphate. This observation suggests that even with concomitant vitamin D or calcitriol therapy, long-term oral phosphate supplementation may lead to the development of hypercalcaemic hyperparathyrodism. Caution is recommended when relatively large doses of phosphate are used to treat hypophosphataemic osteomalacia of diverse causes.

Hydatid disease. An unusual cause of chronic monarthritis.

We describe a patient with granulomatous synovitis secondary to osseus hydatid disease that manifested with chronic monarthritis, eosinophilia, and urticaria.

Chronic ascites in late onset systemic lupus erythematosus with antiphospholipid antibodies.

Because doctors are reluctant to diagnose systemic lupus erythematosus (SLE) in elderly patients, the initial diagnosis in this age group is usually tardy. Furthermore, the presenting manifestations in these patients are commonly atypical. We describe a 72-year-old woman in whom chronic ascites with antiphospholipid antibodies was the initial predominant manifestation of subsequently fatal SLE. Only 13 cases of chronic lupus ascites have been reported in the English and French literature. Our patient represents the first case reported in an elderly person.