The use of autologous platelet-rich plasma (PRP) versus no intervention in women with low ovarian reserve undergoing fertility treatment: a non-randomized interventional study.

PURPOSE: To investigate the impact of a 3-month course of intracortical injections of autologous platelet-rich plasma (PRP) upon ovarian reserve markers versus no intervention in women with low ovarian reserve prior to undergoing assisted reproductive technology (ART). METHODS: Prospective controlled, non-randomized comparative study conducted in a private fertility clinic, in Venezuela. Women with abnormal ovarian reserve markers (FSH, AMH and AFC) who declined oocyte donation were allocated to one of the following groups according to patient choice: monthly intracortical ovarian PRP injections for three cycles, or no intervention. Primary outcomes were the change in FSH, AMH and AFC pre- and post-treatment. Secondary outcomes included the number of oocytes collected and fertilized, biochemical/clinical pregnancy rates and miscarriage and live birth rates. RESULTS: Eighty-three women were included, of which 46 received PRP treatment and 37 underwent no intervention. Overall median age was 41 years (IQR 39-44). There were no demographic differences between the study groups. At the 3-month follow-up, women treated with PRP experienced a significant improvement in FSH, AMH and AFC, whereas there was no change in the control group. Furthermore, overall rates of biochemical (26.1% versus 5.4%, P = 0.02) and clinical pregnancy (23.9% versus 5.4%, P = 0.03) were higher in the PRP group, while there was no difference in the rates of first trimester miscarriage and live birth between groups. CONCLUSION: PRP injections are effective and safe to improve markers of low ovarian reserve prior to ART, although further evidence is required to evaluate the impact of PRP on pregnancy outcomes.

Intake of total omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study.

BACKGROUND AND AIMS: The evidence about the benefits of omega-3 fatty acid intake on coronary heart disease (CHD) is not consistent. We thus aimed to assess the relation between dietary intake of total omega-3 fatty acids (from plant and marine foods) and marine polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS AND RESULTS: The analysis included 41,091 men and women aged 20-69 years, recruited from 1992 to 1996 and followed-up until December 2004. Omega-3 fatty acid intake was estimated from a validated dietary questionnaire. Only participants with definite incident CHD event were considered as cases. Cox regression models were used to assess the association between the intake of total omega-3 fatty acids, EPA or DHA and CHD. A total of 609 participants (79% men) had a definite CHD event. Mean intakes of total omega-3 fatty acids, EPA and DHA were very similar in the cases and in the cohort, both in men and women. In the multivariate adjusted model, omega-3 fatty acids, EPA and DHA were not related to incident CHD in either men or women. The hazard ratios (HR) for omega-3 were 1.23 in men (95% CI 0.94-15.9, p = 0.20); and 0.77 in women (95% CI 0.46-1.30, p = 0.76). CONCLUSION: In the Spanish EPIC cohort, with a relatively high intake of fish, no association was found between EPA, DHA and total omega-3 fatty acid intake and risk of CHD.

Daily effects of air pollutants and pollen types on asthma and COPD hospital emergency visits in the industrial and Mediterranean Spanish city of Cartagena

Background: Associations found in time-series studies on hospital emergency room (ER) visits due to asthma and chronic obstructive pulmonary disease (COPD) with single air pollutants show some lack of consistency. The respiratory effects of aeroallergens in the air pollution mix are not well established. Non-linear relationships of different airborne pollen types with certain respiratory diseases have also been described. We aim to study the short-term effects of major air pollutants and aeroallergen pollen on asthma and COPD hospital ER visits in the industrial and Mediterranean Spanish city of Cartagena during1995-1998. Methods: The association of asthma and COPD to ER visits with mean levels of sulphur and nitrogen dioxides (SO2 and NO2), total suspended particles (TSP), ozone (O3), and the main allergenic airborne pollen types were analysed using Poisson regression with Generalised Additive Models, taking into account delayed effects and adjusting for long-term trends, seasonality, weather conditions, holidays and flu notifications. Results: Multipollutant models showed a similar relative risk (RR) increase (in %), of around 5% in asthma and COPD ER visits per 10 microg/m3 SO2 increments. The risk of an ER visit for the sameNO2 increment was 2.6% for asthma and 3.3% for COPD. Visits to the ER due to asthma showed a positive increase with both Urticaceae and Poaceae levels, but did not substantially modify the previous percentages(AU)

Daily effects of air pollutants and pollen types on asthma and COPD hospital emergency visits in the industrial and Mediterranean Spanish city of Cartagena.

BACKGROUND: Associations found in time-series studies on hospital emergency room (ER) visits due to asthma and chronic obstructive pulmonary disease (COPD) with single air pollutants show some lack of consistency. The respiratory effects of aeroallergens in the air pollution mix are not well established. Non-linear relationships of different airborne pollen types with certain respiratory diseases have also been described. We aim to study the short-term effects of major air pollutants and aeroallergen pollen on asthma and COPD hospital ER visits in the industrial and Mediterranean Spanish city of Cartagena during 1995-1998. METHODS: The association of asthma and COPD to ER visits with mean levels of sulphur and nitrogen dioxides (SO(2) and NO(2)), total suspended particles (TSP), ozone (O(3)), and the main allergenic airborne pollen types were analysed using Poisson regression with Generalised Additive Models, taking into account delayed effects and adjusting for long-term trends, seasonality, weather conditions, holidays and flu notifications. RESULTS: Multipollutant models showed a similar relative risk (RR) increase (in %), of around 5% in asthma and COPD ER visits per 10 µg/m(3) SO(2) increments. The risk of an ER visit for the same NO(2) increment was 2.6% for asthma and 3.3% for COPD. Visits to the ER due to asthma showed a positive increase with both Urticaceae and Poaceae levels, but did not substantially modify the previous percentages. CONCLUSIONS: Air levels of SO(2) and NO(2) were associated with a substantial increased risk in ER visits due to asthma and COPD. The inclusion of Poaceae and Urticaceae pollen did not alter that association.

Dialysis after kidney transplant failure: do patients start in a worse condition than the general population with chronic kidney disease?

BACKGROUND: Patients with renal graft dysfunction constitute an increasingly prevalent group of end-stage kidney disease (ESKD) patients that require dialysis therapy. These patients have special characteristics that set them apart from the ESKD general population. The aim of this study was to analyse the clinical condition and evolution of patients entering dialysis with a failed kidney graft at the time of restarting dialysis and over a year of therapy according to the K/DOQI guidelines, and to compare them with incidental patients with end-stage kidney disease. We also investigated whether the modality of kidney replacement therapy may determine the clinical improvement of transplant patients. MATERIAL AND METHOD: This is a retrospective observational study of 106 patients with ESKD followed up in the Ramon y Cajal Hospital. They were classified in two groups. Group one was made up of 50 failed native kidney patients who started dialysis between 2000 and 2009. Group two was comprised of 56 transplant patients with graft dysfunction who returned to dialysis between 1997 and 2009. We studied parameters of kidney function, anaemia, calcium-phosphorus metabolism, cardiovascular risk factors and nutritional status at the time both groups started on dialysis and one year later. RESULTS: Both groups had a similar clinical status at the time they started on dialysis in most of the parameters analysed with the exception of anaemia. This was more severe in transplant patients, despite the fact that transplant patients received a higher dose of erythropoietin than non-transplant patients. One year later the main difference between both groups was the residual kidney function rate, higher in non-transplant patients. There were no significant differences in the parameters analysed in patients with a failed graft according to the modality of kidney replacement therapy. CONCLUSION: Failed transplant patients start dialysis with more severe anaemia than patients entering dialysis for the first time. Twelve months later both groups present a similar clinical condition with the exception of residual kidney function, higher in failed native kidney patients. The method of dialysis treatment after kidney transplant failure did not have a bearing on the clinical improvement of our patients.

Population-based cancer registries in Spain and their role in cancer control.

Population-based cancer registries (PBCRs) are a key element for cancer control. They measure cancer incidence and trends, provide indicators for planning and evaluating cancer control activities, and undertake research. The first two PBCRs in Spain were established in Zaragoza in 1960 and Navarre in 1970, but it was from 1980 to 1995 when most of the existing registries went into operation. Today, 26.5% of the Spanish population is served by a cancer registry. All registries' quality-control indicators meet the inclusion criteria for comparability and quality of data required by the International Agency for Research on Cancer, and indeed some fulfil most of the excellence criteria for gold standard certification. After their initiation into recording accurate and complete information targeted at ascertaining cancer incidence in their catchment areas, PBCRs are progressively broadening their scope and becoming increasingly involved in collecting and analysing additional data on patient care, diagnosis, disease stage, treatment and follow-up. Spanish registries have become actively engaged in research projects, domestic and international, at a rate that has risen remarkably in the past decade. The creation of a network of Spanish cancer registries is being considered, with the aim of its becoming a key player in developing standards for cancer registration, providing training and technical assistance, undertaking quality audits and promoting the use of cancer surveillance data to reduce the burden of cancer in Spain.

Estudio del tiempo de procesamiento de un sistema preanalítico en un laboratorio de atención primaria / Study of the processing time of a preanalytical system in a primary care laboratory

Objetivo: adaptación del sistema preanalítico modular (MPA) conectado a un sistema modular analítico SWA (Roche Diagnostics) y estudio de la optimización del tiempo de procesamiento preanalítico basándose en cambios en el proceso de alicuotación. Material y métodos: descripción de la arquitectura y de la configuración funcional del sistema preanalítico. Estudio observacional basado en la carga de trabajo diaria, comparando los tiempos y las velocidades de procesamiento de las muestras tal y como está definido el sistema en la actualidad, con los que se obtendrían de 2 modelos teóricos basados en la agrupación de destinos correspondientes a los analizadores de inmunoquímica. Resultados: se comentan los cambios en el diseño inicial del sistema. El tiempo de procesamiento para una media de 1.364 especímenes/día es de 255,9 min. La velocidad de procesamiento resultante es de 319 especímenes/h para una media de 0,95 alícuotas/espécimen. El tiempo de procesamiento se reduce un 18,3% con la combinación más favorable de los modelos teóricos. Conclusiones: el diseño actual del sistema preanalítico se adecua a las características del laboratorio (volumen de muestras elevado y horario laboral limitado), aunque deben realizarse mejoras. Con el modelo teórico más favorable, no se disminuye suficientemente el tiempo de procesamiento como para permitir hacer una alícuota destinada al archivo de muestras. Se necesitan estudios suplementarios que incluyan el tiempo total de procesamiento de las muestras en los analizadores, para comprobar si una futura agrupación de analizadores de inmunoquímica y, en concreto, cuál de ellas aumentaría la eficiencia del proceso total(AU)

Objective: Adjustment of a Modular Preanalytics (MPA) and Modular Analytics System SWA (Roche Diagnostics) to our laboratory. A study was carried out in order to optimize the turnaround times of the process, changing the system configuration to reduce the number of aliquots. Material and methods: Description of the preanalytical system and its operational configuration. The study of turnaround times of the preanalytical process on the daily workload was compared with 2 theoretical models in which the serum destined for the immunoassay analyzers were grouped in 2 different ways. Results: There are comments about the changes in the initial design of the system. For an average workload of 1364 serum samples/day, the turnaround time of the current configuration was 255.9 min. The resulting rate was 319 samples/h with an average of 0.95 aliquots/sample. In the theoretical models, with the most favorable combination of aliquots, the reduction in turnaround time was 18.3%. Conclusions: The present design of the preanalytical system was adapted to the characteristics of our laboratory, with a large number of samples and with limited working hours, however, improvements should be made. Even the more favorable theoretical model does not allow us to make an aliquot for storage of serum in our work time. Additional studies are needed, including the total turnaround time of process in the immunoassay analyzers, to verify if a possible grouping of immunoassay analyzers and, in particular. which of them, will increase the efficiency of the overall analytical process(AU)

Fibrosis pulmonar idiopática: en busca de un tratamiento eficaz / No disponible

No disponible

[Sociodemographic differences in adherence to the Mediterranean dietary pattern in Spanish populations]. / Diferencias sociodemográficas en la adhesión al patrón de dieta mediterránea en poblaciones de España.

OBJECTIVES: Lower social classes tend to eat a less healthy diet. The aim of this study was to compare adherence to the Mediterranean dietary pattern among different demographic and social groups in the adult population. METHODS: A cross-sectional study was performed in southern and northern regions of Spain in healthy volunteers (15,634 men and 25,812 women), aged 29-69 years, who were members of the European Prospective Investigation on Cancer cohort in Spain. Nine groups of food were included in the definition of the Mediterranean diet: vegetables and garden products, fruits, pulses, cereals, red meat, fish, olive oil, milk and milk products, and wine. Two techniques were used in the analysis: comparison of the mean daily intake of each group and calculation of an overall score for all the foods according to educational level and original social class. RESULTS: Groups with the lowest educational levels consumed more cereals and pulses and lower quantities of vegetables, olive oil (women), milk and milk products (men). Wine consumption was positively associated with education in women and was negatively associated in men. Calculation of a score to measure overall adherence to the Mediterranean dietary pattern eliminated differences according to each food category. No variations were found according to educational level, but small differences were found in original social class. The adherence score was lowest in young adults and women and was slightly higher in the south than in the north of Spain. CONCLUSIONS: The results suggest that the Mediterranean dietary pattern is fairly uniform, at least in the adult population of the regions included in this study.

Diferencias sociodemográficas en la adhesión al patrón de dieta mediterránea en poblaciones de España / Sociodemographic differences in adherence to the Mediterranean dietary pattern in Spanish populations)

Objetivos: Los grupos de nivel social más bajo tienen habitualmente una dieta menos saludable. El objetivo de este estudio es comparar la adhesión al patrón de dieta mediterránea entre diferentes grupos demográficos y sociales de la población adulta. Métodos: Se realizó un estudio transversal en regiones del sur y norte de España, en voluntarios sanos (15.634 varones y 25.812 mujeres) de 29 a 69 años de edad, miembros de la cohorte EPIC en España. Se tuvo en cuenta el consumo de nueve grupos de alimentos para definir el patrón de dieta mediterránea: vegetales, frutas, legumbres, cereales, carne roja, pescado, aceite de oliva, leche y productos lácteos y vino. Se aplicaron dos técnicas de análisis: comparación de la media diaria de consumo de cada grupo, y el cálculo de un escore global para todos los alimentos, por nivel educacional y clase social de origen. Resultados: Los grupos de nivel educacional más bajo consumen más cereales y legumbres, pero menos vegetales, aceite de oliva (las mujeres), leche y productos lácteos (los varones). El consumo de vino está positivamente asociado con la educación en las mujeres y negativamente asociado en los varones. Calculando una puntuación para medir la adhesión global al patrón de dieta mediterránea, las diferencias por cada grupo de alimentos se compensan, y no hay variaciones según el nivel educacional, aunque existen pequeñas diferencias en la clase social de origen (22,52 en la clase más baja y 21,98 en la clase más alta). El índice de adhesión es más bajo en los adultos jóvenes y mujeres, y ligeramente más alto en las poblaciones del sur (23,53 en Murcia) que en las del norte de España (21,64 en Asturias). Conclusiones: Los resultados sugieren que el patrón de dieta mediterránea es bastante uniforme, al menos en las poblaciones adultas de las áreas incluidas en el estudio (AU)

Objectives: Lower social classes tend to eat a less healthy diet. The aim of this study was to compare adherence to the Mediterranean dietary pattern among different demographic and social groups in the adult population. Methods: A cross-sectional study was performed in southern and northern regions of Spain in healthy volunteers (15,634 men and 25,812 women), aged 29-69 years, who were members of the European Prospective Investigation on Cancer cohort in Spain. Nine groups of food were included in the definition of the Mediterranean diet: vegetables and garden products, fruits, pulses, cereals, red meat, fish, olive oil, milk and milk products, and wine. Two techniques were used in the analysis: comparison of the mean daily intake of each group and calculation of an overall score for all the foods according to educational level ang original social class. Results: Groups with the lowest educational levels consumed more cereals and pulses and lower quantities of vegetables, olive oil (women), milk and milk products (men). Wine consumption was positively associated with education in women and was negatively associated in men. Calculation of a score to measure overall adherence to the Mediterranean dietary pattern eliminated differences according to each food category. No variations were found according to educational level, but small differences were found in original social class. The adherence score was lowest in young adults and women and was slightly higher in the south than in the north of Spain. Conclusions: The results suggest that the Mediterranean dietary pattern is fairly uniform, at least in the adult population of the regions included in this study (AU)

Regulation of Ca2+-sensitive adenylyl cyclase in gonadotropin-releasing hormone neurons.

In immortalized GnRH neurons, cAMP production is elevated by increased extracellular Ca2+ and the Ca2+ channel agonist, BK-8644, and is diminished by low extracellular Ca2+ and treatment with nifedipine, consistent with the expression of adenylyl cyclase type I (AC I). Potassium-induced depolarization of GT1-7 neurons causes a dose-dependent monotonic increase in [Ca2+]i and elicits a bell-shaped cAMP response. The inhibitory phase of the cAMP response is prevented by pertussis toxin (PTX), consistent with the activation of G(i)-related proteins during depolarization. Agonist activation of the endogenous GnRH receptor in GT1-7 neurons also elicits a bell-shaped change in cAMP production. The inhibitory action of high GnRH concentrations is prevented by PTX, indicating coupling of the GnRH receptors to G(i)-related proteins. The stimulation of cAMP production by activation of endogenous LH receptors is enhanced by low (nanomolar) concentrations of GnRH but is abolished by micromolar concentrations of GnRH, again in a PTX-sensitive manner. These findings indicate that GnRH neuronal cAMP production is maintained by Ca2+ entry through voltage-sensitive calcium channels, leading to activation of Ca2+-stimulated AC I. Furthermore, the Ca2+ influx-dependent activation of AC I acts in conjunction with AC-regulatory G proteins to determine basal and agonist-stimulated levels of cAMP production.

Autocrine regulation of gonadotropin-releasing hormone secretion in cultured hypothalamic neurons.

Episodic hormone secretion is a characteristic feature of the hypothalamo-pituitary-gonadal system, in which the profile of gonadotropin release from pituitary gonadotrophs reflects the pulsatile secretory activity of GnRH-producing neurons in the hypothalamus. Pulsatile release of GnRH is also evident in vitro during perifusion of immortalized GnRH neurons (GT1-7 cells) and cultured fetal hypothalamic cells, which continue to produce bioactive GnRH for up to 2 months. Such cultures, as well as hypothalamic tissue from adult rats, express GnRH receptors as evidenced by the presence of high-affinity GnRH binding sites and GnRH receptor transcripts. Furthermore, individual GnRH neurons coexpress GnRH and GnRH receptors as revealed by double immunostaining of hypothalamic cultures. In static cultures of hypothalamic neurons and GT1-7 cells, treatment with the GnRH receptor antagonist, [D-pGlu1, D-Phe2, D-Trp(3,6)]GnRH caused a prominent increase in GnRH release. In perifused hypothalamic cells and GT1-7 cells, treatment with the GnRH receptor agonist, des-Gly10-[D-Ala6]GnRH N-ethylamide, reduced the frequency and increased the amplitude of pulsatile GnRH release, as previously observed in GT1-7 cells. In contrast, exposure to the GnRH antagonist analogs abolished pulsatile secretion and caused a sustained and progressive increase in GnRH release. These findings have demonstrated that GnRH receptors are expressed in hypothalamic GnRH neurons, and that receptor activation is required for pulsatile GnRH release in vitro. The effects of GnRH agonist and antagonist analogs on neuropeptide release are consistent with the operation of an ultrashort-loop autocrine feedback mechanism that exerts both positive and negative actions that are necessary for the integrated control of GnRH secretion from the hypothalamus.

Muscarinic regulation of intracellular signaling and neurosecretion in gonadotropin-releasing hormone neurons.

Agonist activation of cholinergic receptors expressed in perifused hypothalamic and immortalized GnRH-producing (GT1-7) cells induced prominent peaks in GnRH release, each followed by a rapid decrease, a transient plateau, and a decline to below basal levels. The complex profile of GnRH release suggested that acetylcholine (ACh) acts through different cholinergic receptor subtypes to exert stimulatory and inhibitory effects on GnRH release. Whereas activation of nicotinic receptors caused a transient increase in GnRH release, activation of muscarinic receptors inhibited basal GnRH release. Nanomolar concentrations of ACh caused dose-dependent inhibition of cAMP production that was prevented by pertussis toxin (PTX), consistent with the activation of a plasma-membrane Gi protein. Micromolar concentrations of ACh also caused an increase in phosphoinositide hydrolysis that was inhibited by the M1 receptor antagonist, pirenzepine. In ACh-treated cells, immunoblot analysis revealed that membrane-associated G(alpha q/11) immunoreactivity was decreased after 5 min but was restored at later times. In contrast, immunoreactive G(alpha i3) was decreased for up to 120 min after ACh treatment. The agonist-induced changes in G protein alpha-subunits liberated during activation of muscarinic receptors were correlated with regulation of their respective transduction pathways. These results indicate that ACh modulates GnRH release from hypothalamic neurons through both M1 and M2 muscarinic receptors. These receptor subtypes are coupled to Gq and Gi proteins that respectively influence the activities of PLC and adenylyl cyclase/ion channels, with consequent effects on neurosecretion.

Aging and venous thromboembolism influence the pharmacodynamics of the anti-factor Xa and anti-thrombin activities of a low molecular weight heparin (nadroparin).

Venous thromboembolism may be efficiently treated by one single daily administration of a high dose of low molecular weight heparin (LMWH). The present study investigates if the physiological deterioration of renal function associated with normal aging or the presence of an acute venous thromboembolism influences the pharmacodynamic pattern of the anti-factor Xa and anti-thrombin activities. Three groups of 12 subjects were investigated. The first 2 groups were composed of healthy volunteers differing by age (25 +/- 4 and 65 +/- 3 yrs) and creatinine clearance (114 +/- 15 and 62 +/- 6 ml x min(-1)). The third group was composed of patients hospitalized for deep vein thrombosis, having a mean age of 65 +/- 11 yrs and creatinine clearance of 76 +/- 8 ml x min(-1). Nadroparin was administered subcutaneously once daily at the dose of 180 anti-factor Xa IU.kg(-1) for 6 to 10 days. Serial sampling on day 1 and on the last day of administration (day n) allowed the pharmacodynamic parameters of the anti-factor Xa and anti-thrombin activities to be compared at the beginning and at the end of the treatment. The main findings were the following: (1) After repeated administration, a significant accumulation of the anti-factor Xa activity was observed in the healthy elderly and in the patients but not in the healthy young subjects (accumulation factor: 1.3). There was no evidence of accumulation of anti-thrombin activity; (2) There were significant correlations between the clearance of creatinine and the clearance of the anti-factor Xa activity but not with that of the anti-thrombin activity; (3) In the patients, the clearance of the anti-factor Xa and of the anti-thrombin activities were 1.4 and 2 times higher respectively than those calculated in the healthy elderly; (4) The mean ratio of the of anti-factor Xa and anti-thrombin clearances was close to 2 in the healthy subjects but equal to 5.4 in the patients. These results suggest that the mechanisms involved in the clearance of polysaccharide chains which support the anti-thrombin activity are different from those of the anti-factor Xa activity and that the enhanced binding properties of plasma proteins to unfractionated heparin reported in patients presenting an acute venous thromboembolism also exists for LMWH, predominantly for the anti-thrombin activity.