Aryl hydrocarbon receptor interacting protein (AIP) significantly influences prognosis of pancreatic carcinoma.

INTRODUCTION: Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. Aryl hydrocarbon receptor interacting protein (AIP) in one of AHR ligands. The aim of this study is to analyze the prognostic influence of AIP in pancreatic carcinoma. MATERIAL AND METHODS: Retrospective case series with immunohistochemical analysis of AIP. We have estimated a multivariate Cox's model for the outcome (progression free and overall survival). RESULTS: 204 patients were included in the study. As expected prognosis was poor and 67.8% died of disease. As for AIP 9.8% of the cases showed nuclear staining of the epithelial tumor cells and 59.4% a cytoplasmic one. Stroma was stained in 53.1% of the cases. Univariate survival analysis revealed a significantly worse prognosis of patients with cytoplasmic AIP expression (stroma and epithelium), but nuclear expression was associated to a better prognosis. In the multivariate analysis stromal AIP expression was an independent prognosticator of progression free survival, together with pT stage, histological grade and history of diabetes. DISCUSSION: AIP Is a conserved cochaperone protein binding to many proteins. AIP has been proposed as a potential tumor suppressor gene. To date, no study has analyzed the immunohistochemical expression of AIP in pancreatic carcinoma. Our results indicate that both epithelial and stromal cytoplasmic expression of AIP is associated to bad prognosis, while nuclear translocation seems to improve prognosis. CONCLUSION: Although we must deepen into the complex signaling pathways underlying this potential association, our results open a way to inhibiting AHR as a potential target against pancreatic carcinoma.

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

Background Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. Methods Observational retrospective multicenter study. Inclusion criteria: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. Results Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. Conclusion It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here (AU)

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

CD133 + cell infusion in patients with colorectal liver metastases going to be submitted to a major liver resection (CELLCOL): A randomized open label clinical trial.

BACKGROUND: Treatment of liver metastases of colorectal carcinoma is surgical resection. However, only 10-15% of the patients in this context will be candidate for curative resection arising other 10-13% after response to neoadyuvant chemotherapy. In order to perform the liver metastases surgery, it is necessary to have a sufficient remnant liver volume (RLV) which allows maintaining an optimal liver function after resection. Studies on liver regeneration have determined that CD133 + stem cells are involved in liver hypertrophy developed after an hepatectomy with encouraging results. As presented in previous studies, CD133 + stem cells can be selected from peripheral blood after stimulation with G-CSF, being able to obtain a large number of them. We propose to treat patients who do not meet criteria for liver metastases surgery because of insufficient RLV (<40%) with CD133 + cells together with portal embolization, in order to achieve enough liver volume which avoids liver failure. METHODS: /Design: The aim of this study is to evaluate the effectiveness of preoperative PVE plus the administration of CD133 + mobilized from peripheral blood with G-CSF compared to PVE only. SECONDARY AIMS ARE: to compare the grade of hypertrophy, speed and changes in liver function, anatomopathological study of hypertrophied liver, to determine the safety of the treatment and analysis of postoperative morbidity and surveillance. STUDY DESIGN: Prospective randomized longitudinal phase IIb clinical trial, open, to evaluate the efficacy of portal embolization (PVE) together with the administration of CD133 + cells obtained from peripheral blood versus PVE alone, in patients with hepatic metastasis of colorectal carcinoma (CCRHM). DISCUSSION: The number of CD133 + obtained from peripheral blood after G -CSF stimulation will be far greater than the number obtained with direct puncture of bone marrow. This will allow a greater intrahepatic infusion, which could have a direct impact on achieving a larger and quicker hypertrophy. Consequently, it will permit the treatment of a larger number of patients with an increase on their survival. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03803241.

Splenic volume as a biomarker of hepatic damage after chemotherapy in patients with resected colorectal liver metastases (CRLM).

BACKGROUND: Chemotherapy-associated liver injury (CALI) is a matter of concern for hepatobiliary surgeons as it can entail postoperative liver failure after an extensive hepatectomy. Recent studies have taken special interest in liver function parameters which can correlate with CALI to decrease this adverse event. Therefore, the current study investigates the usefulness of splenic volume as a biomarker of CALI through a portal hypertension mechanism, in patients with colorectal liver metastases (CRLM). STUDY DESIGN: We carried out a study in patients with CRLM operated on between 2009 and 2014 in our center. All samples of healthy liver were graded for non-alcoholic fatty liver disease (NAFLD) and sinusoidal obstructive syndrome. Computarized tomography scans for spleen volumetry were analyzed for each patient at CRLM diagnosis, after neoadjuvant chemotherapy, 1 and 6 months after resection. RESULTS: A group of 65 consecutive patients with CRLM of large bowel adenocarcinoma submitted to liver resection were included. Patients receiving neoadjuvant chemotherapy had a greater spleen volume increase than those who did not receive treatment (p = 0.053), finding a statistically significant spleen growth in patients with NAFLD (p = 0.036). There was no correlation between spleen enlargement and postoperative complications or average stay. However, survival was decreased in patients with spleen growth and CALI. CONCLUSIONS: Patients who receive neoadjuvant chemotherapy for liver metastasis surgery have a greater splenic volume increase, which correlates with NAFLD and a lower survival.

Still a place for conventional histopathological analysis in the era of molecular medicine: predicting prognosis of resectable ductal pancreatic adenocarcinoma.

INTRODUCTION: Our aim is to find features that define prognosis in surgically resected ductal pancreatic adenocarcinoma readily accessible in everyday practice. MATERIALS AND METHODS: Longitudinal retrospective case series of pancreatic adenocarcinoma operated with a curative intent in a large tertiary hospital in Madrid between 2009 and 2015. RESULTS: 162 were enrolled. 40.8% survived less than 1 year. Multivariate Cox's regression model revealed that gender, presence of symptoms, T and N stage independently influenced progression-free survival, while overall survival was determined by gender, smoking, presence of symptoms and N stage. Logistic regression analysis revealed that only symptoms at diagnosis could predict death, while gender, symptoms, histopathological type, vessel invasion, T stage and necrosis could independently predict recurrence. DISCUSSION: Our series show that patients with symptomatic disease at the time of diagnosis and females showed a shorter progression-free and overall survival. We herein propose a regression model to predict outcome.

Structural and magnetic properties of core-shell Au/Fe3O4 nanoparticles.

We present a systematic study of core-shell Au/Fe3O4 nanoparticles produced by thermal decomposition under mild conditions. The morphology and crystal structure of the nanoparticles revealed the presence of Au core of d = (6.9 ± 1.0) nm surrounded by Fe3O4 shell with a thickness of ~3.5 nm, epitaxially grown onto the Au core surface. The Au/Fe3O4 core-shell structure was demonstrated by high angle annular dark field scanning transmission electron microscopy analysis. The magnetite shell grown on top of the Au nanoparticle displayed a thermal blocking state at temperatures below TB = 59 K and a relaxed state well above TB. Remarkably, an exchange bias effect was observed when cooling down the samples below room temperature under an external magnetic field. Moreover, the exchange bias field (HEX) started to appear at T~40 K and its value increased by decreasing the temperature. This effect has been assigned to the interaction of spins located in the magnetically disordered regions (in the inner and outer surface of the Fe3O4 shell) and spins located in the ordered region of the Fe3O4 shell.

Alteraciones de la alineación vertebral / Changes in spinal alignment

Las desalineaciones de la columna vertebral constituyen un motivo de consulta muy frecuente en atención primaria y servicios especializados. Las etiologías son diversas e influyen múltiples factores: en la adolescencia, la desalineación más frecuente es la escoliosis, de causa idiopática (80%) y normalmente asintomática. En la edad adulta, la causa más frecuente es la degenerativa. Es importante conocer la historia natural y detectar posibles factores predictivos de progresión. El correcto diagnóstico de las deformidades vertebrales requiere de estudios radiológicos concretos. El grado de deformidad determina el tipo de tratamiento. El objetivo es prevenir la progresión de la deformidad, recuperar la flexibilidad y el balance del cuerpo (AU)

Spinal misalignments are a common reason for consultation at primary care centers and specialized departments. Misalignment has diverse causes and is influenced by multiple factors: in adolescence, the most frequent misalignment is scoliosis, which is idiopathic in 80% of cases and normally asymptomatic. In adults, the most common cause is degenerative. It is important to know the natural history and to detect factors that might predict progression. The correct diagnosis of spinal deformities requires specific imaging studies. The degree of deformity determines the type of treatment. The aim is to prevent progression of the deformity and to recover the flexibility and balance of the body (AU)

Changes in spinal alignment. / Alteraciones de la alineación vertebral.

Spinal misalignments are a common reason for consultation at primary care centers and specialized departments. Misalignment has diverse causes and is influenced by multiple factors: in adolescence, the most frequent misalignment is scoliosis, which is idiopathic in 80% of cases and normally asymptomatic. In adults, the most common cause is degenerative. It is important to know the natural history and to detect factors that might predict progression. The correct diagnosis of spinal deformities requires specific imaging studies. The degree of deformity determines the type of treatment. The aim is to prevent progression of the deformity and to recover the flexibility and balance of the body.

Spanish-Portuguese consensus statement on use of daylight-mediated photodynamic therapy with methyl aminolevulinate in the treatment of actinic keratosis.

INTRODUCTION: Daylight-mediated photodynamic therapy (PDT) is a new type of PDT that is as effective as conventional PDT in grade 1 and 2 actinic keratosis but with fewer adverse effects, resulting in greater efficiency. The climatic conditions in the Iberian Peninsula require an appropriately adapted consensus protocol. OBJECTIVE: We describe a protocol for the treatment of grade 1 and 2 actinic keratosis with daylight-mediated PDT and methyl aminolevulinate (MAL) adapted to the epidemiological and clinical characteristics of Spanish and Portuguese patients and the climatic conditions of both countries. METHODS: Twelve dermatologists from different parts of Spain and Portugal with experience in the treatment of actinic keratosis with PDT convened to draft a consensus statement for daylight-mediated PDT with MAL in these countries. Based on a literature review and their own clinical experience, the group developed a recommended protocol. RESULTS: According to the recommendations adopted, patients with multiple grade 1 and 2 lesions, particularly those at risk of developing cancer, are candidates for this type of therapy. Daylight-mediated PDT can be administered throughout the year, although it is not indicated at temperatures below 10°C or at excessively high temperatures. Likewise, therapy should not be administered when it is raining, snowing, or foggy. The procedure is simple, requiring application of a sunscreen with a protection factor of at least 30 based exclusively on organic filters, appropriate preparation of the lesions, application of MAL without occlusion, and activation in daylight for 2hours. CONCLUSION: This consensus statement represents a practical and detailed guideline to achieve maximum effectiveness of daylight-mediated PDT with MAL in Spain and Portugal with minimal adverse effects.

Variaciones anatómicas del proceso uncinado en tomografía computada multidetector en pacientes con rinosinusitis crónica

Objetivo: Describir la anatomía del proceso uncinado y sus variaciones observadas a través de cortes coronales por tomografía computada multidetector (TCMD) en una población con rinosinusitis crónica. Introducción: Según la literatura científica revisada, no se encontraron estudios sobre las variaciones anatómicas del complejo osteomeatal (COM) en la población adulta colombiana. Los reportes coinciden en que las variaciones anatómicas de este complejo son parte de las causas de la sinusitis crónica refractaria a tratamiento médico, por lo que el presente trabajo se propone estudiar la anatomía de este complejo e identificar sus posibles variaciones anatómicas en pacientes adultos colombianos diagnosticados con sinusitis crónica. Materiales y métodos: Se realizó un estudio descriptivo de corte transversal, observacional y retrospectivo. Para las variables continuas se estimaron medidas de tendencia central y de dispersión, con un intervalo de confianza del 95%, mientras que para las variables categóricas se determinaron las frecuencias y los porcentajes con que se presentaron en la muestra. Resultados: Se contó con 143 casos. De este total, el 53,8% fueron hombres y el 46,2% mujeres. Tanto en el lado derecho como en el izquierdo, el proceso uncinado del hueso etmoides se insertó en la lámina papirácea (el 49,7% y el 53,1% de los hombres y mujeres, respectivamente). La inserción del proceso uncinado en la lámina cribosa del hueso etmoides en el lado derecho fue el segundo en frecuencia (25,2%) y en el lado izquierdo este lugar lo ocupó la inserción en la concha nasal media (23,8%). También se encontró que, en la mayoría de los casos, el proceso uncinado tuvo una orientación lateral (el 51% en el lado derecho y el 56,6% en el lado izquierdo). Conclusión: El proceso uncinado es una estructura anatómica muy variable que se encuentra a cada lado de la cavidad nasal. Presenta diferentes puntos de inserción y tiene cambios en su angulación y distintas longitudes. Es importante tener en cuenta estas variaciones para el manejo quirúrgico de la rinosinusitis crónica.(AU)

Objective: To describe the uncinate process anatomy and its variations observed through coronal, multislice computed tomography (MSCT) in patients with chronic rhinosinusitis. Introduction: As reviewed in the literature, no studies of anatomical variations ostiomeatal complex in Colombian adults were found. The reports agree that the anatomical variations of this complex are part of the causes of chronic sinusitis refractory to medical treatment, which motivated the present work to study the anatomy of this complex and identify possible anatomic variations in adult patients from Colombia, diagnosed with chronic sinusitis. Materials and methods: A descriptive, cross-sectional, observational and retrospective study. Continuous variables were estimated with measures of central tendency and dispersion, with a confidence interval of 95%. Categorical variables were determined with frequencies and percentages. Results: The total sample was 143 cases. In the sample, 53.8% were men and 46.2% were women. Both of the right and left, the uncinate process of the ethmoid was inserted into the lamina papyracea in 49.7% and 53.1% of cases, respectively. The insertion of the uncinate process in the cribriform plate of the ethmoid (T6) had a frequency to the right side of 25.2%, but for the left side was the insertion into the middle nasal concha (T1) (23.8%). In most cases, the uncinate process had a lateral orientation and 51% on the right side and 56.6% on the left side. Conclusion: The uncinate process is a highly variable anatomical structure at each side of the nasal cavity, arranged indifferent insertion sites, changes in angle and different lengths which is important from the point of view of surgical management of chronic rinosinusitis.(AU)

Variaciones anatómicas del proceso uncinado en tomografía computada multidetector en pacientes con rinosinusitis crónica

Objetivo: Describir la anatomía del proceso uncinado y sus variaciones observadas a través de cortes coronales por tomografía computada multidetector (TCMD) en una población con rinosinusitis crónica. Introducción: Según la literatura científica revisada, no se encontraron estudios sobre las variaciones anatómicas del complejo osteomeatal (COM) en la población adulta colombiana. Los reportes coinciden en que las variaciones anatómicas de este complejo son parte de las causas de la sinusitis crónica refractaria a tratamiento médico, por lo que el presente trabajo se propone estudiar la anatomía de este complejo e identificar sus posibles variaciones anatómicas en pacientes adultos colombianos diagnosticados con sinusitis crónica. Materiales y métodos: Se realizó un estudio descriptivo de corte transversal, observacional y retrospectivo. Para las variables continuas se estimaron medidas de tendencia central y de dispersión, con un intervalo de confianza del 95%, mientras que para las variables categóricas se determinaron las frecuencias y los porcentajes con que se presentaron en la muestra. Resultados: Se contó con 143 casos. De este total, el 53,8% fueron hombres y el 46,2% mujeres. Tanto en el lado derecho como en el izquierdo, el proceso uncinado del hueso etmoides se insertó en la lámina papirácea (el 49,7% y el 53,1% de los hombres y mujeres, respectivamente). La inserción del proceso uncinado en la lámina cribosa del hueso etmoides en el lado derecho fue el segundo en frecuencia (25,2%) y en el lado izquierdo este lugar lo ocupó la inserción en la concha nasal media (23,8%). También se encontró que, en la mayoría de los casos, el proceso uncinado tuvo una orientación lateral (el 51% en el lado derecho y el 56,6% en el lado izquierdo). Conclusión: El proceso uncinado es una estructura anatómica muy variable que se encuentra a cada lado de la cavidad nasal. Presenta diferentes puntos de inserción y tiene cambios en su angulación y distintas longitudes. Es importante tener en cuenta estas variaciones para el manejo quirúrgico de la rinosinusitis crónica.

Objective: To describe the uncinate process anatomy and its variations observed through coronal, multislice computed tomography (MSCT) in patients with chronic rhinosinusitis. Introduction: As reviewed in the literature, no studies of anatomical variations ostiomeatal complex in Colombian adults were found. The reports agree that the anatomical variations of this complex are part of the causes of chronic sinusitis refractory to medical treatment, which motivated the present work to study the anatomy of this complex and identify possible anatomic variations in adult patients from Colombia, diagnosed with chronic sinusitis. Materials and methods: A descriptive, cross-sectional, observational and retrospective study. Continuous variables were estimated with measures of central tendency and dispersion, with a confidence interval of 95%. Categorical variables were determined with frequencies and percentages. Results: The total sample was 143 cases. In the sample, 53.8% were men and 46.2% were women. Both of the right and left, the uncinate process of the ethmoid was inserted into the lamina papyracea in 49.7% and 53.1% of cases, respectively. The insertion of the uncinate process in the cribriform plate of the ethmoid (T6) had a frequency to the right side of 25.2%, but for the left side was the insertion into the middle nasal concha (T1) (23.8%). In most cases, the uncinate process had a lateral orientation and 51% on the right side and 56.6% on the left side. Conclusion: The uncinate process is a highly variable anatomical structure at each side of the nasal cavity, arranged indifferent insertion sites, changes in angle and different lengths which is important from the point of view of surgical management of chronic rinosinusitis.

Dissemination of hepatocellular carcinoma in subcutaeous tissue after fine needle aspiration cytology (FNAC).

The hepatocellular carcinoma (HCC) is the fifth most frequent tumor in the world, and the third cause of death related to cancer. Histological samples obtained from diseased liver likely to have HCC are currently prescribed in selected patients in whose imaging studies and tumor markers are not sufficient for the diagnosis. In recent years, a risk of tumoral seeding along needle tract of FNAC to obtain histological samples has been reported. We present a case of tumor implantation of HCC cells in the needle tract, a year and four months after a percutaneous fine needle aspiration cytology (FNAC).

Metabolism of dehydroepiandrosterone sulfate and estrone-sulfate by human platelets.

The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.

Dehydroepiandrosterone prevents the aggregation of platelets obtained from postmenopausal women with type 2 diabetes mellitus through the activation of the PKC/eNOS/NO pathway.

The steroid hormone dehydroepiandrosterone (DHEA), suggested to be a cardioprotector, prevents platelet aggregation in healthy humans. This hormone is reduced in postmenopausal women by 60% of its normal value. Platelets in patients with type 2 diabetes (T2D) are more sensitive to aggregation, which has been attributed to a reduced ability to produce nitric oxide (NO). In light of these precedents and considering that DHEA is able to increase the production of NO in cultured endothelial cells, we suggest that DHEA prevents the aggregation of platelet from postmenopausal women with T2D through the activation of PKC/eNOS/NO/cGMP pathway. To determine the effect of DHEA in platelet aggregation, platelet-rich plasma (PRP) obtained from postmenopausal women with T2D was preincubated with DHEA, and aggregation induced by ADP was determined in the presence or absence of L-NNA (LNG-nitroarginine), Rottlerin, NOS, or PKC delta inhibitors, respectively. Platelet NO production was measured with the fluorescent probe DAF2DA and eNOS activation was determined by Western blot, using an anti-p-eNOS (ser 1177) antibody. DHEA 1) prevented platelet aggregation by 40% compared to control, 2) increased NO production by 63%, 3) increased p-eNOS (phosphorylated endothelial nitric oxide synthase) levels, and 4) increased cGMP production. These effects were reduced in the presence of L-NNA or Rottlerin. DHEA prevents platelet aggregation induced by ADP. This effect is mediated by the activation of the PKCδ/eNOS/NO/cGMP pathway. Our results suggest that DHEA could be considered to be a potential therapeutic tool in the prevention of atherothrombotic processes in postmenopausal women with T2D.

The conversion of dehydroepiandrosterone into androst-5-ene-3beta,17beta-diol (androstenediol) is increased in endometria from untreated women with polycystic ovarian syndrome.

The changes in endometrial homeostasis found in women with polycystic ovarian syndrome (PCOS) could be associated with alterations in the intracrine metabolism of steroid hormones. The uptake of dehydroepiandrosterone-sulphate (DHEA-S), precursor of the intracrine pathway, is achieved by transporters, such as organic anion transporter polypeptides (OATPs), and molecules with oestrogenic activity, such as androst-5-ene-3beta,17beta-diol (androstenediol), can be generated. We aimed to determine androstenediol generation and the expression of OATPs in human endometria throughout the menstrual cycle and in endometria from PCOS women. Endometrial samples were obtained from control women in the proliferative phase (control endometria (CEp), n=7), secretory phase (CEs, n=7), and from PCOS patients (PCOSEp, n=7). The mRNA levels of OATP-B, OATP-D and OATP-E were measured by reverse transcriptase polymerase chain reaction (RT-PCR) and protein levels of OATP-E by immunofluorescence; 3beta-hydroxysteroid dehydrogenase (HSD) by immunohistochemistry/Western blot; the metabolism of DHEA to androstenediol was evaluated by thin layer chromatography-high-performance liquid chromatography (TLC-HPLC). Lower levels of OATP-E transcript were obtained in PCOSEp (p<0.05) compared with CEp, while OATP-E protein levels (p<0.05) and DHEA conversion to androstenediol (p<0.01) were higher in PCOSEp. Lower 3beta-(hydroxysteroid dehydrogenase) HSD protein levels were found in PCOSEp (p<0.05) (Western blot, immunohistochemistry). These results reveal a higher capacity of the endometria from PCOS women to metabolise DHEA to androstenediol, which, coupled with the high oestrogen sensitivity previously found in these endometria, may account for the increase in cell proliferation in PCOSEp already reported.

In situ estrogen metabolism in proliferative endometria from untreated women with polycystic ovarian syndrome with and without endometrial hyperplasia.

The aim of the present investigation was to study whether the endocrinological status of women bearing polycystic ovarian syndrome (PCOS) affects the endometrial in situ steroid metabolism. For this purpose, we evaluated the mRNA levels (RT-PCR), and the activity of steroid metabolic enzymes: P450 aromatase, steroid sulfatase (STS), estrogen sulfotransferase (EST) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in 23 samples of normal endometria (CE), 18 PCOS endometria without treatment (PCOSE), 10 specimens from PCOS women with endometrial hyperplasia (HPCOSE), and 7 endometria from patients with endometrial hyperplasia not associated to PCOS (EH). The data showed lower levels of STS mRNA for PCOSE and HPCOSE (p<0.05, p<0.01, respectively) and of EST for HPCOSE and EH compared to control (p<0.05). However, higher levels for EST mRNA were obtained in PCOSE (p<0.05) versus CE. The mRNA and protein levels for P450 aromatase were undetectable in all analyzed endometria. The relationship between the activities of STS and EST was lower in PCOSE and HPCOSE (p<0.05) versus CE. The ratio between the mRNA from 17beta-HSD type 1/type 2 was higher in PCOSE (p<0.05), whereas, a diminution in the 17beta-HSD type 2 activity was observed in PCOSE (p<0.05). These results indicate that the activity of enzymes related to the steroid metabolism in analyzed PCOSE differ from those found in the CE. Consequently, PCOSE may present an in situ deregulation of the steroid metabolism.

Injury patterns from major urban terrorist bombings in trains: the Madrid experience.

BACKGROUND: Terrorist urban mass casualty incidents (MCI) in the last 3 years have targeted commuter trains at rush hour, producing large numbers of casualties. Civilian care providers are usually not familiar with the types of blast injuries sustained by victims of these MCI. METHODS: We focus on the injury patterns sustained by casualties of the Madrid, 11 March 2004, terrorist bombings, at the seven hospitals that received most victims. Data were gathered of casualties who had injuries other than superficial bruises, transient hearing loss from barotrauma without eardrum perforation, and/or emotional shock. The degree of severity in critical patients was assessed with the ISS. RESULTS: The bombings resulted in 177 immediate fatalities, 9 early deaths, and 5 late deaths. Most survivors had noncritical injuries, but 72 (14%) of 512 casualties assessed had an Injury Severity Score (ISS) >15. The critical mortality rate was of 19.5%. The most frequently injured body regions were the head-neck and face. Almost 50% of casualties had ear-drum perforation, and 60% of them were bilateral. There were 43 documented cases of blast lung injury, with a survival rate of 88.3%. Maxillofacial and open long-bone fractures were most prevalent. Gustillo's grade III of severity predominated in tibia-fibular and humeral fractures. Upper thoracic fractures (D1-6 segment) represented 65% of all vertebral fractures and were associated with severe blast to the torso. Severe burns were uncommon. Eye injuries were frequent, although most were of a mild-to-moderate severity. Abdominal visceral lesions were present in 25 (5%) patients. A multidisciplinary approach was necessary in most operated patients, and orthopedic trauma procedures accounted for 50% of the caseload in the first 24 h. CONCLUSIONS: Ninety-three percent of the fatalities of the Madrid trains terrorist bombings were immediate, and most survivors had noncritical injuries. Closed doors increased the immediate fatality rate in the trains. Severely wounded casualties presented specific patterns of injuries, some of them life-threatening and unusual in other types of trauma mechanisms. Ear-lobe amputations and upper thoracic spine fractures were markers of critical injuries.