[Diagnostic accuracy of blood pressure determination in clinics in control of hypertension: Proposal of new cut-off values]. / Precisión diagnóstica de la determinación de la presión arterial en consulta en el control del hipertenso: Propuesta de nuevos valores de corte.

AIM: This study seeks to determine the optimal cut-off values for the determination of the blood pressure in the clinic as a follow-up test in Primary Care practice. DESIGN: A total of 153 hypertensive patients under 80years of age who met inclusion and exclusion criteria for the study, were subjected to ambulatory monitoring of their blood pressure for 24hours (ABPM). After which two clinic-based measurements were obtained. With the results obtained from the clinic, and taking the ABMP as a reference, the ROC curve was calculated choose the optimal cut-off point. The agreement between both measurements was determined by the intraclass correlation coefficient and the Bland-Altman equation. A validation study was then carried out with the objective of diagnosing whether or not the hypertensive patient was in control. RESULTS: The optimal cut-off values were 137mmHg for systolic BP (sensitivity: 89.3%; specificity: 72.2%) and 84mmHg for diastolic blood pressure (sensitivity: 79.4%; specificity: 72.3%). The agreement in the diagnosis of control between clinic-based measurement and ABPM was 58.9% (Kappa: 0.418). CONCLUSION: The optimal cut-off value of the diastolic BP for follow-up is lower than the values currently established.

An easy-to-perform, culture-free Campylobacter point-of-management assay for processing plant applications.

AIMS: Current culture-based methods for detection and determination of Campylobacter levels on processed chickens takes at least 2 days. Here we sought to develop a new complete, low-cost and rapid (approximately 2·5 h) detection system requiring minimal operator input. METHODS AND RESULTS: We observed a strong correlation between culture-based cell counts and our ability to detect either Campylobacter jejuni or Campylobacter coli by loop-mediated isothermal amplification from the same samples. This knowledge was used to develop a rapid and simple five-step assay to quantify Campylobacter, which was subsequently assessed for its specificity, reproducibility and accuracy in quantifying Campylobacter levels from processed chickens. The assay was found to be highly specific for C. jejuni and C. coli and was capable of distinguishing between samples that are either within or exceeding the industry set target of 6000 Campylobacter colony forming units (CFU) per carcass (equivalent to 12 CFU per ml of chicken rinse) with >90% accuracy relative to culture-based methods. CONCLUSIONS: Our method can reliably quantify Campylobacter counts of processed chickens with an accuracy comparable to culture-based assays but provides results within hours as opposed to days. SIGNIFICANCE AND IMPACT OF THE STUDY: The research presented here will help improve food safety by providing fast Campylobacter detection that will enable the implementation of real-time risk management strategies in poultry processing plants to rapidly test processed chickens and identify effective intervention strategies. This technology is a powerful tool that can be easily adapted for other organisms and thus could be highly beneficial for a broad range of industries.

¿Por qué los pacientes no retiran todos los medicamentos y productos sanitarios que les son prescritos por el médico? / Why do patients not withdraw all the medicines and health products prescribed to them by the doctor?

Introducción: la e-receta finalizó su implantación en la Comunidad Valenciana (CV) en septiembre de 2013, observándose que el paciente no retiraba parte de los medicamentos que tenía prescritos, por lo que se diseña un estudio para estudiar las diversas incidencias que pudieran ser la causa. Objetivos: analizar y cuantificar las incidencias detectadas en la dispensación de las e-receta prescritas a los pacientes en farmacia comunitaria de la CV. Métodos: estudio observacional, transversal, prospectivo multicéntrico de base poblacional de las incidencias detectadas en las dispensaciones de las e-receta. Población diana: pacientes mayores de 18 años o cuidadores. Resultados: se registraron 22.983 solicitudes de medicamentos o productos sanitarios (MPS) correspondientes a 6.621 pacientes. De los MPS disponibles para ser dispensados se rechazaron un 12,0 %. Las discrepancias entre lo que el médico prescribió y el paciente entendió supusieron el 19,0 % de los rechazos. Las distintas razones relacionadas con el inccumplimiento fueron el 32,3 % de los medicamentos rechazados (MR). En aquellos medicamentos en los que el paciente debía pagar una aportación el rechazo fue ligeramente mayor (12,2 %) que en el caso de los que no. Conclusiones: La dispensación de MPS prescritos a través de la e-receta permite identificar problemas relacionados con medicamentos (PRM) que inciden sobre la falta de adherencia y las discrepancias con lo prescrito en la receta electrónica

Introduction: The e-receipt finished its implantation in the Valencian Community (CV) in September 2013, observing that the patient did not withdraw part of the medicines prescribed, so a study is designed to find out the various incidents that could be the cause. Objectives: To analyze and quantify the incidences detected in the dispensation of the e-recipes prescribed to patients in community pharmacy (FC) de la CV. Methods: Observational, cross-sectional, prospective multicenter population-based study of the incidences detected in the dispensations of the e-recipes. The target population: patients over 18 years of age, or caregivers. Results: 22,983 requests for medicines or health products (HP) were recorded for 6,621 patients. Of the medicines or HP available for dispensing, 12.0% were rejected. • Discrepancies between what the doctor prescribed and what the patient understood accounted for 19.0% of refusals. • The different reasons related to non-compliance were 32.3% of medicines or health products (HP). In those medicines where the patient had to pay a contribution, the rejection was slightly higher (12.2%) than in the case of those who did not. Conclusions: The dispensing of prescribed medicines/HP through the e-prescription makes it possible to identify drug related problem DRPs that affect the lack of adherence and discrepancies with what is prescribed in the electronic prescription

Re-purposing bridging flocculation for on-site, rapid, qualitative DNA detection in resource-poor settings.

Developing molecular diagnostics in resource-poor settings is challenging. As such, we purpose-built a novel bridging flocculation assay for qualitative evaluation of isothermally amplified DNA by naked eye. The flocculation assay was dependent on pH, DNA polymer amounts and lengths. The method was first applied to the rapid and sensitive detection of important plant pathogens and subsequently extended to other pathogens across the animal kingdom to demonstrate the wide applications of our approach.

[Percutaneous gastrostomy complicated with abdominal wall hematoma; severe anemia secondary to percutaneous endoscopic gastrostomy]. / Gastrostomía percutánea complicada con hematoma de pared abdominal; anemización severa secundaria a gastrostomía endoscópica percutánea.

Endoscopic percutaneous gastrostomy (PEG) is a safe and effective procedure that offers clear advantages over nasogastric tube feeding to ensure adequate nutrition in patients with swallowing problems who have an intact digestive tract. With proper placement and monitoring methodology there are few complications in both the peritrack procedure as in the long run. However, despite being considered a safe technique it is not devoided of serious complications. We report a patient with dysphagia, requiring percutaneous endoscopic gastrostomy placement developing a severe anemia with severe subcutaneous hematoma, given the exceptional case and literature review.

Manejo de la hipotermia accidental severa / Management of severe accidental hypothermia

La hipotermia accidental es una patología ambiental con unos principios básicos de clasificación y reanimación que sirven tanto para el medio montañoso, marítimo o urbano. Esta patología ha formado parte, junto a la acidosis y la coagulopatía, de la famosa «tríada letal» de las víctimas traumáticas en situación crítica. En su manejo y asistencia está implicada toda una cadena asistencial que se extiende desde la medicina de urgencia prehospitalaria hasta la medicina intensiva, llegando incluso hasta la cirugía cardiaca y/o a los programas de circulación extracorpórea. Una buena clasificación prehospitalaria del grado de hipotermia facilitará su manejo inicial y evitará traslados interhospitalarios o secundarios innecesarios. Lo fundamental es trasladar, con la mayor urgencia posible, a las víctimas hipotérmicas en asistolia o fibrilación ventricular hasta aquellos hospitales que tengan la capacidad tecnológica adecuada para el tratamiento de estas especiales situaciones clínicas. Este artículo, trata de sentar las bases que faciliten un manejo adecuado de la hipotermia accidental desde la primera asistencia prehospitalaria hasta tratamiento final hospitalario, incluyendo la reanimación y el recalentamiento con circulación extracorpórea (AU)

Accidental hypothermia is an environmental condition with basic principles of classification and resuscitation that apply to mountain, sea or urban scenarios. Along with coagulopathy and acidosis, hypothermia belongs to the lethal triad of trauma victims requiring critical care. A customized healthcare chain is involved in its management, extending from on site assistance to intensive care, cardiac surgery and/or the extracorporeal circulation protocols. A good classification of the degree of hypothermia preceding admission contributes to improve management and avoids inappropriate referrals between hospitals. The most important issue is to admit hypothermia victims in asystolia or ventricular fibrillation to those hospitals equipped with the medical technology which these special clinical scenarios require. This study attempts to establish the foundations for optimum management of accidental hypothermia from first emergency care on site to treatment in hospital including, resuscitation and rewarming with extracorporeal circulation (AU)

[Management of severe accidental hypothermia]. / Manejo de la hipotermia accidental severa.

Accidental hypothermia is an environmental condition with basic principles of classification and resuscitation that apply to mountain, sea or urban scenarios. Along with coagulopathy and acidosis, hypothermia belongs to the lethal triad of trauma victims requiring critical care. A customized healthcare chain is involved in its management, extending from on site assistance to intensive care, cardiac surgery and/or the extracorporeal circulation protocols. A good classification of the degree of hypothermia preceding admission contributes to improve management and avoids inappropriate referrals between hospitals. The most important issue is to admit hypothermia victims in asystolia or ventricular fibrillation to those hospitals equipped with the medical technology which these special clinical scenarios require. This study attempts to establish the foundations for optimum management of accidental hypothermia from first emergency care on site to treatment in hospital including, resuscitation and rewarming with extracorporeal circulation.

Parada cardíaca por hipotermia accidental y resucitación cardiopulmonar prolongada / Cardiac arrest due to accidental hypothermia and prolonged cardiopulmonary resuscitation

En la parada cardíaca por hipotermia la reanimación cardiopulmonar debe prolongarse hasta que se recupere una temperatura corporal normal. Existen diversos métodos de recalentamiento. En teoría, los métodos más cruentos son los de elección en los casos de parada cardíaca porque con ellos se consigue un recalentamiento más veloz, pero su supuesta superioridad sobre otros métodos menos cruentos no está demostrada. Presentamos un caso de hipotermia accidental con parada cardíaca que se trató con masaje cardíaco ininterrumpidamente durante 3h, lo que constituye la reanimación cardiopulmonar con éxito más larga notificada hasta ahora en España. Para recalentar el cuerpo se utilizó una combinación de métodos poco cruentos: recalentamiento activo externo con una tobera de aire caliente, lavado gástrico y vesical con suero caliente e infusión de suero fisiológico caliente. Este caso demuestra que es posible tratar satisfactoriamente la parada cardíaca por hipotermia mediante estos métodos de recalentamiento, rápidos de instaurar y accesibles en cualquier hospital (AU)

In cardiac arrest produced by accidental hypothermia, cardiopulmonary resuscitation must be prolonged until normal body temperature is achieved. There are different rewarming methods. In theory, the more invasive ones are elective in patients with cardiac arrest because of their higher rewarming speed. However, it has not been proven that these methods are better than the non-invasive ones. We present a case report of a patient with cardiac arrest due to accidental hypothermia who was treated without interruption for three hours with heart massage. This is the longest successful cardiopulmonary resuscitation known up-to-date in Spain. In order to rewarm the body, a combination of non-invasive methods was used: active external rewarming with convective warm air, gastric and bladder lavage with warm saline solution and intravenous warm saline infusion. This case shows that it is possible to treat hypothermic cardiac arrest successfully through these rewarming methods, which are both easy to apply and feasible in any hospital (AU)

[Cardiac arrest due to accidental hypothermia and prolonged cardiopulmonary resuscitation]. / Parada cardíaca por hipotermia accidental y resucitación cardiopulmonar prolongada.

In cardiac arrest produced by accidental hypothermia, cardiopulmonary resuscitation must be prolonged until normal body temperature is achieved. There are different rewarming methods. In theory, the more invasive ones are elective in patients with cardiac arrest because of their higher rewarming speed. However, it has not been proven that these methods are better than the non-invasive ones. We present a case report of a patient with cardiac arrest due to accidental hypothermia who was treated without interruption for three hours with heart massage. This is the longest successful cardiopulmonary resuscitation known up-to-date in Spain. In order to rewarm the body, a combination of non-invasive methods was used: active external rewarming with convective warm air, gastric and bladder lavage with warm saline solution and intravenous warm saline infusion. This case shows that it is possible to treat hypothermic cardiac arrest successfully through these rewarming methods, which are both easy to apply and feasible in any hospital.

Bactericidal activity of copper and niobium-alloyed austenitic stainless steel.

Biofouling and microbiologically influenced corrosion are processes of material deterioration that originate from the attachment of microorganisms as quickly as the material is immersed in a nonsterile environment. Stainless steels, despite their wide use in different industries and as appliances and implant materials, do not possess inherent antimicrobial properties. Changes in hygiene legislation and increased public awareness of product quality makes it necessary to devise control methods that inhibit biofilm formation or to act at an early stage of the biofouling process and provide the release of antimicrobial compounds on a sustainable basis and at effective level. These antibacterial stainless steels may find a wide range of applications in fields, such as kitchen appliances, medical equipment, home electronics, and tools and hardware. The purpose of this study was to obtain antibacterial stainless steel and thus mitigate the microbial colonization and bacterial infection. Copper is known as an antibacterial agent; in contrast, niobium has been demonstrated to improve the antimicrobial effect of copper by stimulating the formation of precipitated copper particles and its distribution in the matrix of the stainless steel. Thus, we obtained slides of 3.8% copper and 0.1% niobium alloyed stainless steel; subjected them to three different heat treatment protocols (550 degrees C, 700 degrees C, and 800 degrees C for 100, 200, 300, and 400 hours); and determined their antimicrobial activities by using different initial bacterial cell densities and suspending solutions to apply the bacteria to the stainless steels. The bacterial strain used in these experiments was Escherichia coli CCM 4517. The best antimicrobial effects were observed in the slides of stainless steel treated at 700 degrees C and 800 degrees C using an initial cell density of approximately 10(5) cells ml(-1) and phosphate-buffered saline as the solution in which the bacteria came into contact with copper and niobium-containing steel.

Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells.

Although ovaries serve as the primary source of estrogen for pre-menopausal women, after menopause estrogen biosynthesis from circulating precursors occurs in peripheral tissues by the action of several enzymes, 17beta-hydroxysteroid dehydrogenase 1 (17beta-HSD1), aromatase and estrogen sulfatase. In the breast, both normal and tumoral tissues have been shown to be capable of synthesizing estrogens, and this local estrogen production can be implicated in the development of breast tumors. In these tissues, estradiol (E(2)) can be synthesized by three pathways: (1) estrone sulfatase transforms estrogen sulfates into bioactive estrogens, (2) 17beta-HSD1 converts estrone (E(1)) into E(2), (3) aromatase which converts androgens into estrogens is also present and contributes to the in situ synthesis of active estrogens but to a far lesser extent than estrone sulfatase. Quantitative assessment of E(2) formation in human breast tumors indicates that metabolism of estrone sulfate (E(1)S) via the sulfatase pathway produces 100-500 times more E(2) than androgen aromatization. Breast tissue also possesses the estrogen sulfotransferase involved in the conversion of estrogens into their sulfates that are biologically inactive. In the present review, we summarized the action of the 19-nor-progestin nomegestrol acetate (NOMAC) on the sulfatase, 17beta-HSD1 and sulfotransferase activities in the hormone-dependent MCF-7 and T47-D human breast cancer cell lines. Using physiological doses of substrates NOMAC blocks very significantly the conversion of E(1)S to E(2). It inhibits the transformation of E(1) to E(2). NOMAC has a stimulatory effect on sulfotransferase activity in both cell lines, with a strong stimulating effect at low doses but only a weak effect at high concentrations. The effects on the three enzymes are always stronger in the progesterone-receptor rich T47-D cell line as compared with the MCF-7 cell line. Besides, no effect is found for NOMAC on the transformation of androstenedione to E(1) in the aromatase-rich choriocarcinoma cell line JEG-3. In conclusion, the inhibitory effect provoked by NOMAC on the enzymes involved in the biosynthesis of E(2) (sulfatase and 17HSD pathways) in estrogen-dependent breast cancer, as well as the stimulatory effect on the formation of the inactive E(1)S, can open attractive perspectives for future clinical trials.

An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells.

The specific pharmacological profile of the 19-norprogestin nomegestrol acetate (NOMAC) is, at least in part, defined by its pattern of binding affinities to the different steroid hormone receptors. In the present study, its affinity to the progesterone receptor (PgR), the androgen receptor (AR) and the estrogen receptor (ER) was re-evaluated and compared to those obtained for progesterone (P) and several progestins. The characteristics of binding to the PgR in rat uterus were determined and Ki were found to be roughly similar with 22.8 and 34.3 nM for NOMAC and P, respectively. The binding characteristics of 3H-NOMAC were also determined and compared to that of 3H-ORG2058 with Kd of 5 and 0.6 nM, respectively for rat uterus and 4 and 3 nM, respectively for human T47-D cells. Structure-affinity and -activity relationships were studied on a variety of compounds related to NOMAC in order to assess its specificity as a progestin. The effects of NOMAC on the binding of androgen to the AR were investigated, using rat ventral prostate as target model. Contrary to what was observed for MPA, the RBA of NOMAC was found to decline with time, showing anti-androgenic rather than androgenic potential, a result that was confirmed in vivo. Regarding the ER, since none of the progestins were able to compete with estrogen for binding in rat uterus as well as in Ishikawa cells, the induction of alkaline phosphatase activity (APase) was used as an estrogen-specific response. It confirmed the intrinsic estrogenicity of progestins derived from 19-nor-testosterone (19NT), norethisterone acetate (NETA), levonorgestrel (LNG) or norgestimate (NGM) and others. In contrast, all P and 19-norP derivatives remained inactive. Finally, to complete this overview of NOMAC at the sex steroid receptor levels, the lack of estrogenic or estrogenic-like activity was checked out in different in vitro models. Data from this study have demonstrated that NOMAC is a progestin that has greater steroid receptor selectivity compared to MPA or some other synthetic progestins. It may provide a better pharmacological profile than those progestins currently in use in HRT and OC.

In vitro and in vivo models for the evaluation of potent inhibitors of male rat 17alpha-hydroxylase/C17,20-lyase.

The C(17,20)-lyase is a key enzyme in the biosynthesis of androgens by both the testes and adrenals. A complete inhibition of this enzyme would provide an alternative means of androgen suppression for the treatment of prostatic cancers. In the present study, the inhibitory effects of new non-steroidal compounds were tested in vitro on rat C(17,20)-lyase versus abiraterone, a reference steroidal inhibitor. Their activities were also evaluated in vivo on plasma testosterone (T) and luteinizing hormone (LH) levels and on testes, adrenals, seminal vesicles (SV) and ventral prostate (VP) weights after 3 days of oral treatment to adult male rats (50mg/kg per day p.o.). Inhibition in the nanomolar range was obtained with TX 977, the lead racemate product in this series, and optimization is ongoing based on a slight dissociation observed between its two diastereoisomers, TX 1196-11 (S) and TX 1197-11 (R). These non-steroidal compounds (including YM 55208, a reference competitor) proved to be more active in vivo than abiraterone acetate in this model, but the observed impact on adrenal weight suggests that the specificity of lyase inhibition versus corticosteroid biosynthesis deserves further investigations with this new class of potentially useful agents for the treatment of androgen-dependent prostate cancer.

Diferencias en el efecto de priming negativo en la edad: un metaanálisis / Differences in the negative priming effect in aging: a meta-analysis

El presente trabajo es una actualización del metaanálisis realizado por Verhaeghen y De Meersman 1, dada la inconsistencia encontrada en sus resultados. Se incluyeron en los análisis todos los trabajos sobre diferencias en priming negativo y edad: los trabajos incluidos por Verhaeghen y De Meersman hasta 1997 (21 de identificación y 8 de localización) y los nuevos hasta la actualidad (con un total de 33 de identificación y 8 de localización). Los resultados señalan la inexistencia de diferencias entre los dos grupos de edad (jóvenes y personas mayores) en el efecto de priming negativo (tanto en priming negativo de identificación como en priming negativo de localización), lo que parece resolver la ambigüedad de las conclusiones anteriores. Se discuten las implicaciones teóricas sobre la posible presencia/ausencia de un déficit inhibitorio asociado con la edad, medido a través del efecto de priming negativo (AU)

In vitro and in vivo models for the evaluation of new inhibitors of human steroid sulfatase, devoid of residual estrogenic activity.

The goal of our research project is to develop a new class of orally active drugs, estrone sulfatase inhibitors, for the treatment of estrogen-dependent (receptor positive) breast cancer. Several compounds were synthesized and their pharmacological potencies explored. Based on encouraging preliminary results, three of them, TX 1299, TX 1492 and TX 1506 were further studied in vitro as well as in vivo. They proved to be strong inhibitors of estrone sulfatase when measured on the whole human JEG-3 choriocarcinoma and MCF-7 breast cancer cells and their IC(50)s found to be in the range of known standard inhibitors. Their residual estrogenic activity was checked as negative in the test of induction of alkaline phosphatase (APase) activity in whole human endometrial adenocarcinoma Ishikawa cells. In addition, their effect on aromatase activity in JEG-3 cells was also examined, since the goal of inhibiting both sulfatase and aromatase activities appears very attractive. However, it has been unsuccessful so far. Then, in vivo potencies of TX 1299, the lead compound in our chemical series, were evaluated in comparison with 6,6,7-COUMATE, a non-steroidal standard, in two different rat models and by oral route. First, the absence of any residual estrogenic activity for these compounds was checked in the uterotrophic model in prepubescent female rats. Second, antiuterotrophic activity in adult ovariectomized rat supplemented with estrone sulfate (E(1)S), showed that both compounds were potent inhibitors, the power of TX 1299 relative to 6,6,7-COUMATE being around 80%. This assay was combined with uterine sulfatase level determination and confirmed the complete inhibition of this enzyme within the target organ. Preliminary studies indicated that other non-steroid compounds in the Théramex series were potent in vitro and in vivo inhibitors of estrone sulfatase in rats and further studies are in progress.

Metástasis cutánea de adenocarcinoma de ovario / Cutaneous metastasis from ovarian adenocarcinoma

Mujer de 67 años, sin antecedentes patológicos de interés, que consultó por la aparición en abdomen de placas eritematovioláceas con patrón reticular y aspecto contusiforme. Destacaba la presencia en la superficie de las mismas de lesiones papulovesiculosas aisladas de contenido serosanguinolento. El estudio histopatológico demostró que se trataba de metástasis cutáneas de un adenocarcinoma ovárico (AU)

[Efficacy of quinagolide in the treatment of a patient with hypophyseal resistance to thyroid hormones]. / Eficacia de la quinagolida en el tratamiento de un paciente con resistencia hipofisaria a hormonas tiroideas.

The pituitary resistance to thyroid hormones (PRTH) is not very frequent and well-known entity, their treatment it continues being topic of controversy. In this work we have evaluated the quinagolida effectiveness in the treatment of it unites patient with (PRTH). The relationship among thyroid stimulating hormone (TSH) and free triiodothyronine (FT3) it was used as marker of the thyroid resistance and of the response to the treatment. The concentrations of TSH and FT3 were normalized after adding quinagolida to methimazole. These results suggest that the quinagolida could be an useful drug in the treatment of this pathology, next to the classic treatments.