Epidural analgesia in laparoscopic radical prostatectomy / Analgesia epidural en la prostatectomía radical laparoscópica

Introduction: Epidural analgesia is an effective technique for postoperative pain relief. Our aim in this retrospective study was to assess the postoperative pain control and complications relating to epidural technique in laparoscopic radical prostatectomy (LRP). Material and methods: A retrospective analysis of 193 patients who underwent LRP, in which epidural analgesia was the postoperative pain approach, was performed. The procedure is generally performed under combined anesthesia. Data collected was postoperative pain data; appearance of neurological disorders (Bromage scale was used for motor weakness assessment); data related to the epidural technique and possible difficulties when performing it; data on epidural infusion; catheter-related complications; hospital stay, postoperative complications, and outcome. Results: Firstly, average VAS at rest was 1.2 ± 1.6; and upon movement, average VAS was 1.9 ± 1.8 during the hospital stay. Secondly, complications related to epidural technique appeared in 37 % of patients. There were 3 cases of hematic puncture; 3 accidental catheter disconnections; 1 dural puncture, and 1 subdural block. As for neurological secondary effects of local anesthetics in the epidural technique, 56 patients (30.1 %) presented with motor block of one or both lower extremities after surgery, and 5 (2.7 %) with paresthesia. Statistical analysis showed that motor weakness was not related to age, weight, type of local anesthetic used, infusion rate, level of epidural puncture nor length of catheter within the epidural space (p > 0.05). Conclusion: Postoperative epidural analgesia offers excellent analgesic quality but it can be associated with several complications secondary to the use of local anesthetics, which could disagree with the terms of Fast-track surgery. New techniques like the TAP block could offer the same analgesic quality, without the epidural's technique potential complications (AU)

Objetivos: La analgesia epidural es una técnica eficaz para el control del dolor postoperatorio. Nuestro objetivo en este estudio retrospectivo fue evaluar el control del dolor postoperatorio mediante la escala visual analógica del dolor (EVA) y las complicaciones relacionadas con la técnica epidural, en la prostatectomía radical laparoscópica (PRL). Material y métodos: Llevamos a cabo un análisis retrospectivo de 193 pacientes sometidos a PRL, en los que se realizó la técnica epidural analgésica para el control del dolor postoperatorio. El procedimiento se hizo bajo una anestesia combinada. Registramos los datos relacionados con el dolor postoperatorio; la aparición de sintomatología neurológica (la escala de Bromage se utilizó para evaluar la debilidad motora); datos relacionados con la técnica epidural y posibles dificultades al realizarla; datos sobre la infusión epidural, como tipo de anestésico local utilizado; complicaciones relacionadas con el catéter y complicaciones postoperatorias asociadas al mismo, estancia hospitalaria y resultado. Resultados: En primer lugar, durante la estancia hospitalaria de los pacientes, el EVA promedio en reposo fue 1,2 ± 1,6; y durante el movimiento, el EVA promedio fue de 1,9 ± 1,8. En segundo lugar, las complicaciones relacionadas con la técnica epidural aparecieron en el 37 % de los pacientes. Hubo 3 casos de punción hemática; 3 desconexiones accidentales del catéter, 1 punción dural y 1 bloqueo subdural. En cuanto a las complicaciones neurológicas debidas a los efectos secundarios de los anestésicos locales en la técnica epidural, 56 (30,1 %) pacientes presentaron bloqueo motor de una o ambas extremidades inferiores después de la cirugía y 5 (2,7 %) refirieron parestesias. No hubo ninguna complicación neurológica que persistiese tras el alta hospitalaria. El análisis estadístico mostró que la debilidad motora no estaba relacionada con la edad, el peso, el tipo de anestésico local utilizado, la velocidad de infusión, el nivel de punción epidural ni la longitud del catéter en el espacio epidural (p > 0,05). Conclusión: La analgesia epidural postoperatoria ofrece una excelente calidad analgésica, pero puede estar asociada a varias complicaciones secundarias al uso de anestésicos locales, lo que podría estar en contraposición con las tendencias actuales de cirugía fastrack. Las nuevas técnicas emergentes podrían ofrecer la misma calidad analgésica evitando las potenciales complicaciones de la técnica epidural (AU)

An activating mutation of GNB1 is associated with resistance to tyrosine kinase inhibitors in ETV6-ABL1-positive leukemia.

Leukemias harboring the ETV6-ABL1 fusion represent a rare subset of hematological malignancies with unfavorable outcomes. The constitutively active chimeric Etv6-Abl1 tyrosine kinase can be specifically inhibited by tyrosine kinase inhibitors (TKIs). Although TKIs represent an important therapeutic tool, so far, the mechanism underlying the potential TKI resistance in ETV6-ABL1-positive malignancies has not been studied in detail. To address this issue, we established a TKI-resistant ETV6-ABL1-positive leukemic cell line through long-term exposure to imatinib. ETV6-ABL1-dependent mechanisms (including fusion gene/protein mutation, amplification, enhanced expression or phosphorylation) and increased TKI efflux were excluded as potential causes of resistance. We showed that TKI effectively inhibited the Etv6-Abl1 kinase activity in resistant cells, and using short hairpin RNA (shRNA)-mediated silencing, we confirmed that the resistant cells became independent from the ETV6-ABL1 oncogene. Through analysis of the genomic and proteomic profiles of resistant cells, we identified an acquired mutation in the GNB1 gene, K89M, as the most likely cause of the resistance. We showed that cells harboring mutated GNB1 were capable of restoring signaling through the phosphoinositide-3-kinase (PI3K)/Akt/mTOR and mitogen-activated protein kinase (MAPK) pathways, whose activation is inhibited by TKI. This alternative GNB1K89M-mediated pro-survival signaling rendered ETV6-ABL1-positive leukemic cells resistant to TKI therapy. The mechanism of TKI resistance is independent of the targeted chimeric kinase and thus is potentially relevant not only to ETV6-ABL1-positive leukemias but also to a wider spectrum of malignancies treated by kinase inhibitors.

Pharmacological inhibition of fatty-acid oxidation synergistically enhances the effect of l-asparaginase in childhood ALL cells.

l-asparaginase (ASNase), a key component in the treatment of childhood acute lymphoblastic leukemia (ALL), hydrolyzes plasma asparagine and glutamine and thereby disturbs metabolic homeostasis of leukemic cells. The efficacy of such therapeutic strategy will depend on the capacity of cancer cells to adapt to the metabolic challenge, which could relate to the activation of compensatory metabolic routes. Therefore, we studied the impact of ASNase on the main metabolic pathways in leukemic cells. Treating leukemic cells with ASNase increased fatty-acid oxidation (FAO) and cell respiration and inhibited glycolysis. FAO, together with the decrease in protein translation and pyrimidine synthesis, was positively regulated through inhibition of the RagB-mTORC1 pathway, whereas the effect on glycolysis was RagB-mTORC1 independent. As FAO has been suggested to have a pro-survival function in leukemic cells, we tested its contribution to cell survival following ASNase treatment. Pharmacological inhibition of FAO significantly increased the sensitivity of ALL cells to ASNase. Moreover, constitutive activation of the mammalian target of rapamycin pathway increased apoptosis in leukemic cells treated with ASNase, but did not increase FAO. Our study uncovers a novel therapeutic option based on the combination of ASNase and FAO inhibitors.

Population declines of tuna and relatives depend on their speed of life.

Larger-bodied species in a wide range of taxonomic groups including mammals, fishes and birds tend to decline more steeply and are at greater risk of extinction. Yet, the diversity in life histories is governed not only by body size, but also by time-related traits. A key question is whether this size-dependency of vulnerability also holds, not just locally, but globally across a wider range of environments. We test the relative importance of size- and time-related life-history traits and fishing mortality in determining population declines and current exploitation status in tunas and their relatives. We use high-quality datasets of half a century of population trajectories combined with population-level fishing mortalities and life-history traits. Time-related traits (e.g. growth rate), rather than size-related traits (e.g. maximum size), better explain the extent and rate of declines and current exploitation status across tuna assemblages, after controlling for fishing mortality. Consequently, there is strong geographical patterning in population declines, such that populations with slower life histories (found at higher cooler latitudes) have declined most and more steeply and have a higher probability of being overfished than populations with faster life histories (found at tropical latitudes). Hence, the strong, temperature-driven, latitudinal gradients in life-history traits may underlie the global patterning of population declines, fisheries collapses and local extinctions.

Evaluación de la seguridad de una arcilla modificada y su extracto de migración en bazo de ratas Wistar expuestas de forma subcrónica / Influence of a subchronical exposure to a modified clay and its migration extract in the spleen of Wistar rats

Las ventajas tecnológicas de la incorporación de arcillas modificadas en polímeros para el envasado de alimentos son bien conocidas, pero aún quedan muchas incertidumbres sobre la seguridad de estos materiales. El Instituto Tecnológico del Embalaje, Transporte y Logística ha desarrollado una arcilla, Clay1, modificando una montmorillonita con una sal de amonio cuaternario. Esta organoarcilla, incorporada al polímero (ácido poliláctico), da lugar a un material nanocompuesto, reforzándose así el material de partida. El principal objetivo de este estudio es evaluar la actividad de biomarcadores de estrés oxidativo en bazo de ratas expuestas durante 90 días a Clay1 (40 mg/kg/día) y al extracto de migración obtenido a partir del material nanocompuesto resultante. Los parámetros evaluados fueron la peroxidación lipídica y las actividades enzimáticas superóxido dismutasa y catalasa. Además, se realizó un análisis del contenido en bazo de los metales más característicos que componen la organoarcilla (Al, Ca, Fe, Mg, Si) para comprobar su posible acumulación. En dicho estudio se trabajó con tres grupos de ratas Wistar (n=10): control (comida estándar + agua como bebida), Clay1 (comida estándar mezclada con 40mg/kg/día de arcilla + agua) y extracto de Clay1 (comida estándar + extracto como bebida). Tras el tiempo de exposición los animales se sacrificaron y se extrajo el bazo. De forma general, no se observaron diferencias significativas en ninguno de los parámetros evaluados con respecto al grupo control, por lo que Clay1 muestra un buen perfil toxicológico respecto a los biomarcadores ensayados con vistas a su uso en la industria alimentaria (AU)

The technological advantages of the incorporation of modified clays into polymers for food packaging are well known. However, there are still many uncertainties about the safety of these materials. The Technological Institute of Packaging, Transport and Logistic has developed Clay1, a modified clay with a quaternary ammonium salt. This organoclay is incorporated into the polymer (polylactic acid), giving a nanocomposite material and reinforcing the bulk material. The aim of this study is to evaluate the activity of several oxidative stress biomarkers in the spleen of rats exposed for 90 days to Clay1 (40 mg/kg/day) and its migration extract obtained from the resultant nanocomposite material. The parameters evaluated were lipid peroxidation and superoxide dismutase and catalase activities. Moreover, the characteristic metallic components of the organoclay (Al, Ca, Fe, Mg, Si) were also analyzed to test the possible accumulation. In this study, three groups of Wistar rats (n=10) were used: control (standard food + water), Clay1 (food with Clay1+water) and Clay1 extract (standard food+ Clay1 extract as water). After the exposure the spleen was removed. In general, no significant differences were observed in any of the parameters evaluated compared to the control group, therefore Clay1 showed a good toxicologic profile regarding the biomarkers assayed for its use in the food industry (AU)

Desarrollo de casos clínicos transversales: experiencia dinamizadora de la Unidad Docente de Toxicología de la Universidad de Barcelona / Development of transversal clinical cases: creating a dynamic experience for the Toxicology Teaching Unit of the Barcelona University

Se ha puesto en marcha un proyecto de innovación docente basado en el desarrollo de casos clínicos transversales a lo largo de las diferentes asignaturas del Grado de Farmacia. El objetivo es favorecer un aprendizaje integrador entre materias del grado, durante la carrera universitaria de los alumnos, mediante la elaboración de material docente adecuado para un uso transversal. También se propone desarrollar un "estilo" de comunicación entre profesores y un nuevo modelo de enseñanza en la universidad, que permita generar estrategias de coordinación del profesorado y de elaboración de materiales de uso común. La Unidad de Toxicología del Departamento de Salud Pública ha sido uno de los dinamizadores de este proyecto. Se ha escogido el alcohol como primer caso, introduciendo un personaje, Sam, un paciente de 20 años, que se inicia muy joven y del que veremos su evolución clínica. Sobre el guion básico del caso clínico, se han propuesto una serie de contenidosymaterialesespecíficosencadaunadelas asignaturas.El proyecto se inició en febrero de 2012, mediante una presentación a los alumnos de la asignatura de Bioquímica de primer curso, de los objetivos, la proyección de un documental, así como la distribución de un díptico informativo, y un posterior seminario. Los profesores consideramos muy satisfactoria y productiva esta experiencia. Creemos, que esta forma de trabajo en grupo colaborativo es una excelente herramienta para el aprendizaje de los alumnos y la formación del profesorado (AU)

A teaching innovation project based on the development of clinical cases across different subjects of Pharmacy Degree has been launched. The aim of this project is to promote integrative learning between the subjects, along the academic career, bydevelopingteachingmaterialssuitablefortransversaluse. Italso aims to develop a "style" of communication among teachers and a new model of teaching at the University by generating strategies for teachers' coordination and development of common teaching materials. The Toxicology Unit of the Department of Public Health has been one of the promoters of this project. Alcohol was chosen as first case by introducing a character, Sam, a patient of 20 years, who started very young in alcohol consumption and his clinical course will be seen along the different years. On the basic script of the case, a number of specific contents have been proposed to be covered in each subject. The project started in February 2012 with a presentation to the students of the first year degree, in the subject of Biochemistry, the objectives, a documentary film, the distribution of an informative leaflet and subsequent seminar. Teachers considered the experience as very satisfying and productive and trusted that the way of working in a collaborative group is an excellent tool for student's learning and teacher's training (AU)

Effect of the addition of industrial by-products on Cu, Zn, Pb and As leachability in a mine sediment.

A series of incubation and leaching experiments were performed to assess the feasibility of three industrial by-products (red gypsum (RG), sugar foam (SF) and ashes from the combustion of biomass (ACB)) to reduce the leachability of Cu, Pb, Zn and As in a sediment of São Domingos mine (Portugal). The changes in the element solid phase speciation were also evaluated by applying a sequential extraction procedure. All amendments significantly reduced the leachability of Zn and Cu, whereas the treatment with RG+SF+ACB also decreased the mobility of As. The reduction in Cu leachability was especially remarkable. This could be due to the great affinity of carbonates (included in SF and SF+ACB amendments) to precipitate with Cu, and maghemite and rutile (RG amendment) for acting as relevant sorbents for Cu. Pb was the least mobile element in the sediment and none of the treatments reduced its mobility. The sequential extraction reveals that the amendments induced a significant decrease in the concentration of elements associated with the residual fraction. Cu, Pb and As are redistributed from the residual fraction to the Al, Fe, and Mn hydr(oxides) fraction and Zn from the residual fraction to the water/acid soluble, exchangeable and bound to carbonates pool.

Racial disparity in estrogen receptor positive breast cancer patients receiving trimodality therapy.

INTRODUCTION: We assessed racial differences in progression-free survival (PFS) and overall survival (OS) in relation to subtype in uniformly treated stage II-III breast cancer patients. METHODS: We reviewed records of 582 patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 and evaluated the effect of demographic, tumor, and treatment characteristics on PFS and OS. RESULTS: Median follow up was 44.7 months. 24% of patients were black and 76% white. All had mastectomy and PMRT; 98% had chemotherapy; Estrogen receptor (ER)+ patients received endocrine therapy. Black patients were more likely to have ER- (56% vs. 38%, p=0.0001), progesterone receptor (PR)- (69% vs. 54%, p = 0.002), and triple negative (TN) (46% vs. 24%, p < 0.0001) tumors. Overall, black patients had worse PFS (60.6% vs. 78.3%, p = 0.001) and OS (72.8% vs. 87.7%, p < 0.0001). There was no racial difference in PFS (p = 0.229 and 0.273 respectively) or OS (p = 0.113 and 0.097 respectively) among ER- or TN. Among ER+, black patients had worse PFS (55% vs. 81%, p < 0.001) and OS (73% vs. 91%, p < 0.0001). The difference in PFS was seen in the ER+/PR+/HER2- subgroup (p = 0.002) but not ER+/PR-/HER2- (p = 0.129), and in the post-menopausal ER+/HER2- subgroup (p = 0.004) but not pre/peri-menopausal ER+/HER2- (p = 0.150). CONCLUSIONS: Black women had worse survival outcomes in this cohort. This disparity was driven by (1) a higher proportion of ER- and TN tumors in black women and (2) worse outcome of similarly treated black women with ER+ breast cancer. The underlying causes of racial disparity within hormone receptor categories must be further examined.

Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer.

NOV-002 (a formulation of disodium glutathione disulfide) modulates signaling pathways involved in tumor cell proliferation and metastasis and enhances anti-tumor immune responsiveness in tumor models. The addition of NOV-002 to chemotherapy has been shown to increase anti-tumor efficacy in animal models and some early phase oncology trials. We evaluated the clinical effects of NOV-002 in primary breast cancer, whether adding NOV-002 to standard preoperative chemotherapy increased pathologic complete response rates (pCR) at surgery, and determined whether NOV-002 mitigated hematologic toxicities of chemotherapy and whether levels of myeloid derived suppressor cells (MDSC) were predictive of response. Forty-one women with newly diagnosed stages II-IIIc HER-2 negative breast cancer received doxorubicin-cyclophosphamide followed by docetaxel (AC â†’ T) every 3 weeks and concurrent daily NOV-002 injections. The trial was powered to detect a doubling of pCR rate from 16 to 32% with NOV-002 plus AC â†’ T (α = 0.05, ß = 80%). Weekly complete blood counts were obtained as well as circulating MDSC levels on day 1 of each cycle were quantified. Of 39 patients with 40 evaluable tumors, 15 achieved a pCR (38%), meeting the primary endpoint of the trial. Concurrent NOV-002 resulted in pCR rates for AC â†’ T chemotherapy higher than previously reported. Patients with lower levels of circulating MDSCs at baseline and on the last cycle of chemotherapy had significantly higher probability of a pCR (P = 0.02). Further evaluation of NOV-002 in a randomized study is warranted.

Risk of locoregional recurrence by receptor status in breast cancer patients receiving modern systemic therapy and post-mastectomy radiation.

We assessed differences in locoregional outcome based on receptor status combinations in a cohort of stage II-III breast cancer patients treated with modern trimodality therapy. Medical records of 582 consecutively treated patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 were reviewed. Rate of local regional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Gray's test and by Fine and Gray's modeling approach. Median follow-up was 44.7 months. Five-year progression-free survival (PFS) was 73.9% and overall survival (OS) was 84%. The cumulative 5-year incidence of LRR as first site of failure was 6.2% (95% CI 4.2-8.7). Five-year cumulative incidence of LRR was 8.6 versus 4.4% for estrogen receptor (ER) negative versus ER positive (P = 0.017), 8.5 versus 3.4% for progesterone receptor (PR) negative versus PR positive (P = 0.011), and 1.7 versus 7.5% for HER2 positive (86% received trastuzamab) versus HER2 negative (P = 0.032). Five-year cumulative incidence of LRR was 11.8% for the triple negative subtype and 3.9% for other receptor combinations (P < 0.001). Among patients whose disease is ER positive, 5-year LRR rate was 7.8 versus 3.4% for PR negative versus PR positive (P = 0.130). The prognostic value of the triple negative and HER2 negative subtypes was maintained on multivariate analysis. In the era of HER-2 targeted therapy, tumors that are HER-2 over expressing and are treated with trastuzumab have a very low rate of LRR. ER negative, PR negative, and triple negative status are associated with increased risk of LRR.

Correlation of GREB1 mRNA with protein expression in breast cancer: validation of a novel GREB1 monoclonal antibody.

Studies of gene regulated by estrogen in breast cancer 1 (GREB1) have focused on mRNA levels with limited evidence about GREB1 protein expression in normal and breast cancer cells. A monoclonal antibody that recognizes GREB1 protein in breast tissues could be applied to correlate protein expression with established mRNA expression data. A hybridoma expressing a murine monoclonal antibody targeting a 119 amino acid peptide specific to human GREB1 was generated. The novel monoclonal GREB1 antibody (GREB1ab) was validated for use in Western blotting as well as immunohistochemical (IHC) applications. GREB1ab detects a 216 kDa protein corresponding to GREB1 in estrogen receptor alpha (ERalpha+) breast cancer cells as well as ERalpha- breast cancer cells transduced with a GREB1 expression vector. GREB1ab specificity was verified using an ERalpha antagonist to prevent GREB1 induction as well as a silencing siRNA targeting GREB1 mRNA. GREB1ab was further validated for detection of GREB1 by IHC in breast cancer cell lines and breast tissue microarrays (TMA). ERalpha+ cell lines were observed to express GREB1 while ERalpha- cell lines did not express detectable levels of the protein. Using breast cancer tissue whole sections, IHC with the GREB1ab identified protein expression in ERalpha+ breast cancer tissue as well as normal breast tissue, with little GREB1 expression in ERalpha- breast cancer tissue. Furthermore, these data indicate that GREB1 mRNA expression correlates well with protein expression. The novel monoclonal GREB1ab is specific for GREB1 protein. This antibody will serve as a tool for investigations focused on the expression, distribution, and function of GREB1 in normal breast and breast cancer tissues.

Potential use of gypsum and lime rich industrial by-products for induced reduction of Pb, Zn and Ni leachability in an acid soil.

This study evaluates the potential use of four industrial by-products (phosphogypsum (PG), red gypsum (RG), sugar foam (SF), and ashes from biomass combustion (ACB)), applied at two rates in single and combined amendments to reduce the mobility and availability of Pb, Zn and Ni in a metal-spiked acid soil. Leaching experiments were done to estimate leachability indexes and assess their effectiveness. Most of the treatments significantly reduced the metal leachability although only a few were effective for all metals. Based on principal component and cluster analysis, sugar foam (SF) and a mixture of RG and ACB (RG+ACB), both applied at high rate, were selected as first choices to reduce mobility and availability of the three metals. Metal sorption mechanisms involved in the reduction of their leachability were identified using scanning electron microscopy. In the SF-treated samples, the metals were found associated to amorphous Al-hydroxy polymers deposited on phyllosilicates and organic matter particles. In the (RG+ACB)-treated samples, Pb, Zn, and traces of Ni were found associated to Fe/Ti oxide phases with a significant concentration of S, suggesting the formation of metal-sulfate ternary complexes.

Assessment of the use of industrial by-products for induced reduction of As, and Se potential leachability in an acid soil.

Four industrial by-products (phosphogypsum, PG; red gypsum, RG; sugar foam, SF and ashes from the combustion of biomass, ACB) were evaluated as possible amendments for reducing the leachability and bioavailability of As and Se in a metalloid-spiked acidic soil. The treatments were applied as single, double and triple amendments and at two different rates. The effectiveness of the treatments was evaluated after a series of leaching experiments using a chelating agent (DTPA solution) or a weak acidification (acetic acid at pH 4.93). The most effective treatments (ACB and RG, both applied at high rate) were identified by means of Cluster Analysis using the leachability indexes. Different sorption mechanisms involved in the overall reduction of metalloid leachability were identified using scanning electron microscopy (SEM-BSE and SEM-EDS). In the ACB-treated samples, Se was found associated to organic matter aggregates and to Fe compounds. In the RG-treated samples, EDS analyses showed that As and Se were associated to Fe/Ti (hydr)oxides phases which are present not only in the by-product as maghemite and rutile, but also in the soil as hematite and goethite. In addition, the application of RG induced the formation of non-crystalline Al-hydroxy polymers with As and Se in their composition.

Breast specimen orientation.

Lumpectomy specimens are commonly divided into six sides: superficial, deep, superior, inferior, medial, and lateral. Orienting stitches are placed on the specimen during surgery to allow reorientation by pathology. Despite those efforts, specimen disorientation may occur. The aim of this study was to assess the correlation in orientation between surgeons and pathologists. Lumpectomy specimens were routinely oriented. An additional Prolene suture was randomly placed by the surgeon on one side to be localized by pathology. The results were recorded and the disorientation rate calculated. Specimen size and presence of skin and/or muscle were also recorded. There were 122 lumpectomy specimens prospectively entered. Average specimen volume was 95.5 cm(3). Twenty-four specimens had segments of skin or muscle. The additional sutures were evenly divided between the six sides. The overall disorientation rate was 31.1% (95% confidence interval, 23.1-40.2).The side-specific disorientation rates were 43%, 40%, 35%, 29%, 28%, and 14% for the deep, superficial, lateral, medial, superior, and inferior surfaces, respectively (no statistical difference). Presence of skin or muscle on the specimen did not contribute to better orientation. Specimen volumes, however, were highly associated with orientation. Specimens of <20 cm(3) had a disorientation rate of 78%, while larger specimen had a disorientation rate of 20% (p < .001). Specimen orientation with stitches placed on two surfaces is associated with a high disorientation rate. Better orientation techniques are necessary to minimize the specimen disorientation.

Tumor de Merkel: estudio clínico, histológico,inmunohistoquímico y submicroscópico / Merkel cell tumour: a clinical, histological, inmunochemical and microscopic study

El carcinoma de Merkel es un tumor cutáneo primario de origen neuroendocrino poco frecuente y altamente agresivo tanto a nivel local como a distancia.Su aparición se ha asociado a múltiples etiologías entre las que destaca la exposición a la radiación ultravioleta. Si bien su diagnóstico se basaen los hallazgos clínicos e histológicos, la inmunohistoquímica resulta útil en la confirmación diagnóstica. Debido a su agresividad y mal pronósticoaún hoy no existe un tratamiento estandarizado. Presentamos el caso de una paciente con carcinoma de Merkel de gran tamaño en extremidad inferiorderecha y positividad en la técnica del ganglio centinela, revisando las técnicas diagnósticas y terapéuticas empleadas actualmente en el manejode este tumor (AU)

Merkel cell carcinoma is an inusual and aggressive primary cutaneous tumor with neuroendocrine features. Several etiological factors have been proposedspecially ultraviolet radiation exposition. Although its clinical presentation and characteristic histology are usually enough, immunochemistryfeatures are very helpful to make an accuracy diagnosis. Because of its agressive behaviour and bad outcome there are not standard therapeutic proceduresestablished nowadays. We present a case of a patient with a Merkel cell carcinoma in right lower limb. Sentinel lymph node procedure waspositive. We make a revision of diagnostic and therapeutic procedures used currently (AU)

First Report of Pea enation mosaic virus Infecting Pea and Broad Bean in Spain.

During the spring of 2007, pea plants (Pisum sativum L.) (cvs. Utrillo and Floreta) showing virus-like symptoms were observed in several commercial fields in the southern and eastern regions of Catalonia, Spain. Incidence of symptomatic plants ranged from 5 to 15% and was distributed in both small and large patches. Infected plants exhibited yellow mosaic leaf symptoms that later became translucent. Leaves gradually curled and in some cases developed enations near the veins on the abaxial surface. Plants were "bushy" and had shortened internodes. Infection prior to pod formation resulted in pods that were distorted and stunted (1). The infected leaves and pods were tested by indirect-ELISA with a potyvirus-specific antibody (Agdia, Elkhart, IN) and double-antibody sandwich (DAS)-ELISA with antibodies specific to Pea enation mosaic virus (PEMV), Broad bean wilt virus 1 (BBWV-1), Beet western yellow virus (BWYV), Bean yellow mosaic virus (BYMV), Alfalfa mosaic virus (AMV), and Tomato spotted wilt virus (TSWV) (Loewe Biochemica GmbH, Sauerlach, Germany). PEMV was detected in all 24 symptomatic samples that were collected from 10 locations between March 2007 and March 2008. Thirteen of these samples also tested positive for BWYV, but no differences in symptom expression were observed in plants infected with both viruses or PEMV alone. PEMV was also identified in seven broad bean plants (Vicia faba L.) from three additional locations. These plants expressed interveinal yellow mosaic on leaves and deformed pods. The genomic sequence of PEMV-1 (GenBank Accession No. L04573) was used to design primers to amplify a 451-nt segment of the polymerase gene by reverse transcription (RT)-PCR; PEMV-D (5'-TGACCATGAGTCCACTGAGG-3'), PEMV-R (5'-AGTATCTTCCAACAACCACAT-3'). One ELISA-positive sample was analyzed and the expected size amplicon was generated. Direct sequencing (GenBank Accession No. EU652339) revealed that PEMV-1 and our pea isolate have nucleotide sequence identities of 95%. To our knowledge, this is the first report of PEMV in Spain, which might cause important economical losses since PEMV is an important viral disease of pea and other legumes worldwide. Reference: (1) J. S. Skaf and G. A. Zoeten. No. 372 (No. 257 revised) in: Description of Plant Viruses. AAB, Kew, Surrey, England, 2000.

Snail silencing effectively suppresses tumour growth and invasiveness.

The transcription factor Snail has been recently proposed as an important mediator of tumour invasion because of its role in downregulation of E-cadherin and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led to the consideration of Snail as a potential therapeutic target to block tumour progression. In this report, we provide evidence for this hypothesis. We show that silencing of Snail by stable RNA interference in MDCK-Snail cells induces a complete mesenchymal to epithelial transition (MET), associated to the upregulation of E-cadherin, downregulation of mesenchymal markers and inhibition of invasion. More importantly, stable interference of endogenous Snail in two independent carcinoma cell lines leads to a dramatic reduction of in vivo tumour growth, accompanied by increased tumour differentiation and a significant decrease in the expression of MMP-9 and angiogenic markers and invasiveness. These results indicate that use of RNA interference can be an effective tool for blocking Snail function, opening the way for its application in new antiinvasive therapies.

Past and current trends in soy supplementation: a bibliographic study.

The aim was to determine in what areas the therapeutic application of soy predominates in clinical trials and to assess the emerging fields of its use by means of an analysis of bibliographic resources. A search was performed in the MEDLINE database up to 31 december 2004, limited to the Title/Abstract field, and Clinical Trials as the type of publication. The abstracts from the publications selected (n=86) were reviewed and different variables were assessed. A total of 3280 subjects were included: 15% men and 59% women (71% postmenopausal). The studies were performed basically in healthy individuals (71%). Twenty five percent of the studies investigated plasma levels of different metabolites and 21% determined hormone or lipid profiles. After the year 2000 a new population focus was detected, with the publication of two studies in elite gymnasts and judoists, with positive results. The present observations indicate that soy supplementation in the competitive sports elite may be an emerging application.