Prevalence of Abdominal Aortic Aneurysm in Men Aged 65-74 Years in a Metropolitan Area in North-East Spain.

BACKGROUND: A declining prevalence of AAA and a shift in the distribution towards the older population have been observed during the last decade in Europe. The aim was to estimate the current screening prevalence of AAA in men aged 65-74 years in a metropolitan area in north-east Spain and to identify associated risk factors. METHODS: A cross sectional prevalence study in men registered in L'Hospitalet Primary Healthcare Services (Barcelona, Spain) was performed. There were 619 randomly selected subjects (expected prevalence of aneurysm, 5%; accuracy of estimation, ±2%; loss to follow up, 30%). Exclusion criteria were life expectancy <1 year, limited quality of life, previous diagnosis of AAA, prior aorto-femoral surgery, and non-Caucasian. The following were measured: internal diameter of the infrarenal abdominal aorta using ultrasound, cardiovascular risk factors, personal (heart disease, stroke, peripheral vascular disease) and family history (AAA), physical examination, and blood tests. We estimated the prevalence and 95% confidence interval of AAA, and used logistic regression analysis to identify risk factors for AAA. RESULTS: Among the 651 individuals included in the analysis the prevalence of aneurysm was 2.30% (95% CI, 1.30-3.77%). In the regression analysis, AAA was associated with smoking (0-10, 11-20, or >20 cigarettes/day), diagnosis of myocardial infarction, and being taller than the median (165 cm). CONCLUSIONS: The current screening prevalence of AAA among men aged 65-74 years in a metropolitan area in north-east Spain is similar to that in northern Europe. Smoking, myocardial infarction, and height were associated with the presence of AAA.

DNA copy number profiling reveals extensive genomic loss in hereditary BRCA1 and BRCA2 ovarian carcinomas.

BACKGROUND: Few studies have attempted to characterise genomic changes occurring in hereditary epithelial ovarian carcinomas (EOCs) and inconsistent results have been obtained. Given the relevance of DNA copy number alterations in ovarian oncogenesis and growing clinical implications of the BRCA-gene status, we aimed to characterise the genomic profiles of hereditary and sporadic ovarian tumours. METHODS: High-resolution array Comparative Genomic Hybridisation profiling of 53 familial (21 BRCA1, 6 BRCA2 and 26 non-BRCA1/2) and 15 sporadic tumours in combination with supervised and unsupervised analysis was used to define common and/or specific copy number features. RESULTS: Unsupervised hierarchical clustering did not stratify tumours according to their familial or sporadic condition or to their BRCA1/2 mutation status. Common recurrent changes, spanning genes potentially fundamental for ovarian carcinogenesis, regardless of BRCA mutations, and several candidate subtype-specific events were defined. Despite similarities, greater contribution of losses was revealed to be a hallmark of BRCA1 and BRCA2 tumours. CONCLUSION: Somatic alterations occurring in the development of familial EOCs do not differ substantially from the ones occurring in sporadic carcinomas. However, some specific features like extensive genomic loss observed in BRCA1/2 tumours may be of clinical relevance helping to identify BRCA-related patients likely to respond to PARP inhibitors.

Phenotypic characterization of hereditary epithelial ovarian cancer based on a tissue microarray study.

The pathologic and immunohistochemical features of familial epithelial ovarian cancers are not well understood. We have carried out a comprehensive immunohistochemical study of familial ovarian carcinomas from women with and without BRCA1 or BRCA2 mutations, in order to identify specific and/or common features among these different familial case groups (BRCA1, BRCA2 and non-BRCA1/2) and to identify markers of diagnostic value that might help to select more specific treatments. 73 familial primary ovarian carcinomas were analyzed for the expression of 40 antibodies involved in different genetic pathways using a tissue microarray. Serous carcinomas comprised the majority of all three familial case groups. On the other hand, BRCA1 and BRCA2 carcinomas have similar histopathologic features; i.e. they are often high-grade and are usually diagnosed at a more advanced FIGO stage than non-BRCA1/2 carcinomas. In our series, BRCA1 carcinomas had better clinical evolution and they also more frequently over-expressed PR and P53 than BRCA2 and non-BRCA1/2 carcinomas. Unsupervised cluster analysis and survival analysis identified ERCC1 as a potential marker of better clinical outcome for hereditary epithelial ovarian cancer.

Heterotopic neuroglial tissue as a congenital laterocervical mass: a case report.

Heterotopic neuroglial tissue in the head and neck area is a rare clinical entity which can cause airway obstruction and feeding problems during the neonatal period. The case is presented of heterotopic neuroglial tissue as a congenital laterocervical and intraoral mass in a neonate.

Application of pressurized fluid extraction to determine cadmium and zinc in plants.

A procedure for the determination of Cd and Zn in plants is proposed. The metals are extracted by pressurized fluid extraction (PFE). Operational conditions are: pressure 1500 psi, temperature 75 degrees C, static time 5 min, flush volume 35%, purge time 60s, cycles 1 and 1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (CDTA) 0.01M at pH 4.5 as extracting solution. Determination of Zn is carried out by flame atomic absorption spectroscopy and depending on the concentration level, Cd content is determined by flame or electrothermal atomic absorption spectroscopy. Certified samples of Virginia tobacco leaves, tea leaves, spinach leaves, poplar leaves, a commercial spinach sample (Spinacea oleracea) and genetically modified Arabidopsis thaliana were analysed by the proposed procedure and also by microwave acid digestion and extraction with HCl-Triton X-100. Confidence intervals for Cd and Zn content obtained by the proposed procedure overlap with the certified values. The other procedures, however, provide inaccurate results for Cd. Recoveries obtained for a confidence level of 95% are 96+/-6% and 95+/-5% for Zn and Cd, respectively. Reproducibility of Zn by the proposed procedure is 7% (n=8), similar to the other tests and the detection limit is 2.6 microg. For Cd reproducibility is 8.5% (n=8), better than with HCl-Triton X-100 and similar to acid digestion, the detection limit is 3.5 ng of Cd.

[Infected cholangiocarcinoma]. / Colangiocarcinoma infectado.

Cholangiocarcinomas are malignancies of the biliary duct system. They are encountered in 3 geographic regions: intrahepatic, proximal extrahepatic, and distal extrahepatic. The etiology of most bile duct cancers remains undetermined but some risk factors, like gallstone, have been suggested to play a role by inducing malignant transformation. The prognosis and clinical manifestations depend on the anatomical location and clinical presentation may be confuses or by means of complications like sepsis. We present a case of cholangiocarcinoma which made debut with cholestasis and sepsis in a cholecystectomiced patient, who had a long standing lithiasic cholecystitis.

Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database.

Over the last decade, hematopoietic stem cells transplantation (HSCT) has been increasingly used in the treatment of severe progressive autoimmune diseases. We report a retrospective survey of 183 multiple sclerosis (MS) patients, recorded in the database of the European Blood and Marrow Transplantation Group (EBMT). Transplant data were available from 178 patients who received an autologous graft. Overall, transplant related mortality (TRM) was 5.3% and was restricted to the period 1995-2000, with no further TRM reported since then. Busulphan-based regimens were significantly associated with TRM. Clinical status at the time of transplant and transplant techniques showed some correlations with toxicity. No toxic deaths were reported among the 53 patients treated with the BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan)/antithymocyte globulin (ATG) regimen without graft manipulation, irrespective of their clinical condition at the time of the transplant. Improvement or stabilization of neurological conditions occurred in 63% of patients at a median follow-up of 41.7 months, and was not associated with the intensity of the conditioning regimen. In this large series, HSCT was shown as a promising procedure to slow down progression in a subset of patients affected by severe, progressive MS; the safety and feasibility of the procedure can be significantly improved by appropriate patient selection and choice of transplant regimen.

[Pericardiocentesis in a critical care unit]. / Pericardiocentesis en una Unidad de Cuidados Intensivos.

OBJECTIVE: Study patients diagnosed of pericardial effusion and pericardiocentesis was made. We search the etiology, complications and the cnic's mortality. METHOD: 69 patients of Clinic Hospital of Zaragoza admitted in the critical care unit. RESULTS: We present 69 patients with 20-87 years old, 21 women and 48 men. The most frequent ethiology was neoplasic, 19 patients(27.5%), in most cases lung and breast cancer; 17 (24.6%) yatrogenic and 14 (20.3%) idiopathic. Diagnosis was made previously at ICU in 63.8% (44 patients). Pericardiocentesis was made in the 12 hours after admission in 40 cases (58%), and was superior than 500 cc in 37(53.6%). We registered pericardiocentesis complications in 7 (10.3%).16 patients dead (23%) most of them with pericardial effusion by mechanic cause. CONCLUSION: Was the pericardial effusion etiology has changed last years, the diagnosis is simply and minimum complications in evacuation, because the means and actual monitorization allow to make pericardiocentesis in optimum conditions.

Uniones en hendidura y su papel funcional en el tracto reproductor femenino

En el aparato reproductor femenino se expresan diferentes conexinas (Cxs), proteínas que forman canales de uniones en hendidura (CUH) entre células en contacto, permitiendo la coordinación de respuestas metabólicas y/o eléctricas de grupos celulares. Los CUH jugarían un papel relevante en el desarrollo de las células de la granulosa, ya que permiten la comunicación heteróloga entre el ovocito y las células del cúmulo manteniendo la detención meiótica. En la trompa de Falopio, los CUH coordinarían el batido ciliar del epitelio y la contracción muscular, facilitando el desplazamiento de los gametos y del embrión. En el útero, los CUH conectan a las células miometriales y también a las endometriales. El aumento de CUH durante el preparto permitiría la contracción uterina coordinada facilitando el trabajo de parto al término del embarazo. La expresión de las Cxs es regulada por hormonas, lo que explicaría el perfil de CUH presentes en los diversos tipos celulares del tracto genital en diferentes estadios fisiológicos del sistema reproductor.

Atosiban: perspectivas sobre el manejo etiológico del parto prematuro / Atosiban: perspectives on the etiology management of the premature labor

Analizamos la información disponible respecto del fármaco tocolítico atosiban para evaluar las ventajas y desventajas de esta droga en comparación con las drogas de primera línea, en cuanto a su acción inhibitoria rápida de las contracciones uterinas, su capacidad de prolongar el embarazo y sus efectos adversos sobre la madre, el feto y el recién nacido. Se revisaron 11 artículos de temas preclínicos y 8 estudios, de los cuales 4 corresponden a estudios clínicos controlados aleatorizados. Concluimos que atosiban es comparable a los fármacos ß-agonistas en retrasar el parto hasta en 7 días, sin lograr en forma significativa prolongar el embarazo ni reducir la morbimortalidad neonatal e infantil. Atosiban es mejor tolerado que los ß-agonista, sin embargo dado el aun limitado número de pacientes evaluados, su seguridad para la madre y el feto no han sido completamente establecidas, sugerimos que su uso sea reservado para aquellos pacientes que representen falla o contraindicación del tratamiento habitual

Smoking-related attitudes, characteristics, and opinions in a group of young men with asthma.

UNLABELLED: The objective of this study was to examine the attitudes, characteristics, and opinions about smoking of a group of young asthmatic men. POPULATION AND METHODS: An anonymous, personal questionnaire was administered to 611 young male volunteers who had been diagnosed with asthma (according to the National Heart, Lung, and Blood Institute/World Health Organization Global Initiative for Asthma, 1995) in the respiratory disease and allergy clinics of the Burgos Military Hospital (Spain). This questionnaire contained items related to personal information, asthma characteristics, opinions about smoking, and information related to smoking habits. RESULTS: Six hundred patients with asthma completed the questionnaire. All were men, mean age 20.16 +/- 3.03 years; 189 (31.5%) were smokers and 16 (2.5%) were ex-smokers. Mean age at onset of regular smoking was 16.46 +/- 2 years. Sixty-five percent (65.07%) smoked fewer than 10 cigarettes per day. Most of the smoking asthmatics had mild asthma (58.9%). Eighty-eight percent (88.3%) had moderate dependence. Many of the smoking asthmatics were contemplating stopping smoking (54%), and 59% had tried before to stop. Concern about health was the main reason given for stopping smoking. Asthmatics who smoked had a higher percentage of smokers among family members, friends, and colleagues than nonsmoking asthmatics. Attitudes toward smoking were more permissive among smoking asthmatics. Only 36.64% of the total had received information about tobacco previously. In the sample group, 7% claimed that they did not smoke but their carbon monoxide concentration in exhaled air was 10 ppm or higher. CONCLUSIONS: There were no differences in the onset of the smoking habit between asthmatic and nonasthmatic young people. A large percentage of the smoking asthmatics were considering smoking cessation, motivated mainly by their asthma condition. The group as a whole had little previous information about tobacco.

Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission.

Allogeneic bone marrow transplantation is an effective postremission strategy for patients with acute myelogenous leukemia (AML) in first complete remission (CR). The value of administering consolidation chemotherapy before human leukocyte antigen (HLA)-identical sibling transplantation is not established. Outcomes of patients with AML in first CR receiving no consolidation therapy, standard-dose cytarabine consolidation therapy, and high-dose cytarabine consolidation therapy before HLA-identical sibling transplantation were compared. Five-year treatment-related mortality rates were 30% (95% confidence interval [CI], 18% to 42%) in patients receiving no consolidation chemotherapy, 22% (95% CI, 17% to 28%) in those receiving standard-dose cytarabine consolidation, and 24% (95% CI, 17% to 31%) in those receiving high-dose cytarabine (P = NS). Five-year cumulative incidences of relapse were 19% (10% to 30%), 21% (16% to 27%), and 17% (11% to 24%), respectively (P = NS). Five-year probabilities of leukemia-free survival were 50% (36% to 63%), 56% (49% to 63%), and 59% (50% to 66%), respectively (P = NS). Five-year probabilities of overall survival were 60% (46% to 71%), 56% (49% to 63%), and 60% (51% to 67%), respectively (P = NS). The data indicate that postremission consolidation with cytarabine before allogeneic transplantation for AML in first CR is not associated with improved outcome compared to proceeding directly to transplantation after successful induction. (Blood. 2000;96:1254-1258)

Diagnóstico prenatal de hipoplasis pulmonar mediante el uso de velocimetria Doppler de la circulación arterial pulmonar / Prenatal diagnosis of lung hypoplasia by the use of Doppler velocimeter of lung arterial circulation

Objetivos: Correlacionar la velocimetría doppler de la arteria pulmonar distal con el desarrollo de hipoplasia pulmonar letal. Método: Se utilizó velocimetría doppler de una rama distal de la arteria pulmonar derecha con el objeto de evaluar 11 fetos que fallecieron por hipoplasia pulmonar en el período de recién nacido inmediato, comparando los índices de pulsatilidad y la velocidad máxima con una población constituida por 185 fetos sanos cuyas madres cursaron embarazos sin complicaciones. Resultados: El análisis en el grupo control permitió establecer curvas normales en nuestro medio para el índice de pulsatilidad y la velocidad máxima en arteria pulmonar derecha distal. Se observó una correlación lineal negativa entre el índice de pulsatilidad y la edad gestional, mientras que la velocidad máxima no se modificó con la edad gestional. Los fetos que desarrollaron hipoplasia pulmonar presentaron valores de índice de pulsatilidad por sobre los rangos normales para la edad destional (p< 0,01). La velocidad máxima de los casos afectados por hipoplasia pulmonar no mostró diferencias con el grupo control. Conclusión: Los fetos que desarrollan hipoplasia pulmonar muestran evidencia de aumento de los índices de resistencia de la arteria pulmonar distal. La posible utilidad práctica de este hallazgo requiere de estudios prospectivo que establezcan en forma más precisa la capacidad predictiva de este examen en pacientes con alto riesgo de hipoplasia pulmonar

Daño neurológico de orígen intrauterino: tan lejos, tan cerca / Neurological damage of intrauterine origin: so far, so near

Se examina la relación entre infección intrauterina, parto prematuro, morbilidad neonatal y alteraciones neurológicas a distancia. La evidencia indica la asociación entre la exposición antenal a infecciones y las complicaciones a corto y largo plazo

Differential roles of Akt, Rac, and Ral in R-Ras-mediated cellular transformation, adhesion, and survival.

Multiple biological functions have been ascribed to the Ras-related G protein R-Ras. These include the ability to transform NIH 3T3 fibroblasts, the promotion of cell adhesion, and the regulation of apoptotic responses in hematopoietic cells. To investigate the signaling mechanisms responsible for these biological phenotypes, we compared three R-Ras effector loop mutants (S61, G63, and C66) for their relative biological and biochemical properties. While the S61 mutant retained the ability to cause transformation, both the G63 and the C66 mutants were defective in this biological activity. On the other hand, while both the S61 and the C66 mutants failed to promote cell adhesion and survival in 32D cells, the G63 mutant retained the ability to induce these biological activities. Thus, the ability of R-Ras to transform cells could be dissociated from its propensity to promote cell adhesion and survival. Although the transformation-competent S61 mutant bound preferentially to c-Raf, it only weakly stimulated the mitogen-activated protein kinase (MAPK) activity, and a dominant negative mutant of MEK did not significantly perturb R-Ras oncogenicity. Instead, a dominant negative mutant of phosphatidylinositol 3-kinase (PI3-K) drastically inhibited the oncogenic potential of R-Ras. Interestingly, the ability of the G63 mutant to induce cell adhesion and survival was closely associated with the PI3-K-dependent signaling cascades. To further delineate R-Ras downstream signaling events, we observed that while a dominant negative mutant of Akt/protein kinase inhibited the ability of R-Ras to promote cell survival, both dominant negative mutants of Rac and Ral suppressed cell adhesion stimulated by R-Ras. Thus, the biological actions of R-Ras are mediated by multiple effectors, with PI3-K-dependent signaling cascades being critical to its functions.

Prevention of glutamate neurotoxicity in cultured neurons by 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6), a scavenger of nitric oxide.

Glutamate neurotoxicity in cerebellar neurons in culture is mediated by excessive production of nitric oxide (NO). We anticipated that 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6) could act as a scavenger of NO since it contains a position (C-5) highly activated towards nitration reaction. The aim of this work was to assess whether CR-6 acts as an NO scavenger and prevents glutamate neurotoxicity in cultures of cerebellar neurons. It was shown that CR-6 reduced, in a dose-dependent manner, glutamate-induced formation of cGMP (EC50 approximately 15 microM) and prevented glutamate neurotoxicity. The protection was approximately 50% at 3-10 microM and nearly complete at 100 microM. CR-6 did not prevent glutamate-induced activation of NO synthase, but interfered with the glutamate-NO-cGMP pathway at a later step. CR-6 reduced the formation of cGMP induced by S-nitroso-N-acetylpenicillamine (SNAP), an NO-generating agent, indicating that CR-6 acts as a scavenger of NO in cultured neurons. This was further supported by experiments showing that in neurons treated with CR-6 and glutamate, the 5-nitro derivative of CR-6 was formed, as determined by GC-MS analyses. Moreover, in vitro incubation of CR-6 with SNAP also produced the 5-nitroderivative, thus confirming that CR-6 directly reacts with NO. The results reported indicate that CR-6 acts as an NO scavenger in neurons and prevents glutamate neurotoxicity.

Prenatal exposure to aluminum reduces expression of neuronal nitric oxide synthase and of soluble guanylate cyclase and impairs glutamatergic neurotransmission in rat cerebellum.

Exposure to aluminum (Al) produces neurotoxic effects in humans. However, the molecular mechanism of Al neurotoxicity remains unknown. Al interferes with glutamatergic neurotransmission and impairs the neuronal glutamate-nitric oxide-cyclic GMP (cGMP) pathway, especially in rats prenatally exposed to Al. The aim of this work was to assess whether Al interferes with processes associated with activation of NMDA receptors and to study the molecular basis for the Al-induced impairment of the glutamate-nitric oxide-cGMP pathway. We used primary cultures of cerebellar neurons prepared from control rats or from rats prenatally exposed to Al. Prenatal exposure to Al prevented glutamate-induced proteolysis of the microtubule-associated protein-2, disaggregation of microtubules, and neuronal death, indicating an impairment of NMDA receptor-associated signal transduction pathways. Prenatal exposure to Al reduced significantly the content of nitric oxide synthase and guanylate cyclase and increased the content of calmodulin both in cultured neurons and in the whole cerebellum. This effect was selective for proteins of the glutamate-nitric oxide-cGMP pathway as the content of mitogen-activated protein kinase and the synthesis of most proteins were not affected by prenatal exposure to Al. The alterations in the expression of proteins of the glutamate-nitric oxide-cGMP pathway could be responsible for some of the neurotoxic effects of Al.

Local and systemic liberation of proinflammatory cytokines in ulcerative colitis.

Determination of plasma and tissue cytokine levels in inflammatory bowel disease have frequently resulted in conflicting data. In the present study we determined in patients with ulcerative colitis (UC), the levels of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, interferon (IFN)-gamma, and tumor-necrosis factor (TNF)-alpha liberated by peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) after 48-hr culture with pokeweed mitogen (PWM). IL-1beta, IL-6, IFN-gamma and TNF-alpha in the supernatant were detected by ELISA. Results show low basal levels of IL-1beta secretion by PBMC and LPMC, and a considerable increase after mitogen stimulation. Basal IL-6 production by PBMC was higher in UC patients than in controls [2029 pg/ml, CI95(-165 to 4223) vs 572 pg/ml (-383 to 1527) respectively, P = 0.05] and also after PWM activation [14,995 pg/ml (7759-22,230) vs 6598 pg/ml (3240-9956), respectively, P = 0.05]. In LPMC, no differences in IL-6 secretion were observed. TNF-alpha in activated PBMC of patients with UC was not significantly increased in relation to control (P = 0.09). No constitutive secretion of IFN-gamma was observed in mononuclear cells. IFN-gamma levels secreted by activated LPMC were lower in patients with UC than in controls [1571 pg/ml (-108 to 3251) vs 7953 pg/ml (3851-12,055), respectively, P = 0.03]. These results suggest that IL-6, IL-1beta, and TNF-alpha participate as mediators in the inflammatory phenomena observed in UC. Further studies are necessary to evaluate the role of IFN-gamma in this condition.

Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1.

Two human hSos1 isoforms (Isf I and Isf II; Rojas et al., Oncogene 12, 2291-2300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf II is significantly more effective than hSos1-Isf I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12). The hSos1-Isf II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf I- and Isf II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation. Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf II transfectants consistently exhibited about threefold higher activity than Isf I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf II peptide, but not its corresponding Isf I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion located in proximity to its Grb2 binding region.