Comparative study between 1.5 and 3 Tesla multiparametric MRI systems using the PIRADS version 2 classification in the diagnosis of prostate cancer

Introduction: The 3-Tesla multiparametric MRI (mpMRI) system represents a diagnostic advance for prostate cancer. Our aim is to demonstrate that the results in 1.5-Tesla mpMRI are not inferior compared to the 3-Tesla for the correct diagnosis of prostate cancer. Material and methods: Non-inferiority comparative cross-sectional study between fusion-guided prostate biopsy results. 344 patients with clinical suspicion of prostate cancer (elevated PSA and/or suspicious DRE) and mpMRI interpreted and verified by the same radiologists in all cases, 270 in 1.5-Tesla and 74 in 3-Tesla, with at least one lesion PIRADSv2≥ 3. Exclusion criteria were positive biopsy or previous prostate treatment. We consider malignancy as ISUP≥ 1 and significant tumor as ISUP≥ 2. We used Wilcoxon and t-student test (central tendency measures), diagnostic test (gold standard: ISUP of targeted biopsy), Chi2 test and Z-test (comparison of prevalences and 95%CI malignancy and significant tumor according to mpMRI). Results: Median prostate volume 50cc(IQR:33.5) and PSA 6.11ng/ml(IQR:3.39). Mean age 67.4±8.1years. Number of suspi-cious lesions/patient: mpMRI 1.3 (1.5-Tesla) and 1.5 (3-Tesla). No differences were found between mpMRI (homogeneous and comparable samples). 57% (1.5-Tesla) vs 66% (3-Tesla) of targeted biopsies were malignant, and 34%vs38% were significant tumor, with no significant differences. Se, Sp, PPV and NPV for malignancy (1.5-Tesla vs 3-Tesla) were 96%vs90%, 38%vs44%, 67%vs76%, and 86%vs69%, with no significant differences. Conclusions: There are no significant differences between 1.5-Tesla vs 3-Tesla mpMRI regarding targeted biopsy results. Not to have 3-Tesla mpMRI may not be a limitation to use 1.5-Tesla as a diagnostic test for the better diagnosis of prostate cancer (AU)

Introducción: Los equipos de RM multiparamétrica(RMmp) 3-Tesla suponen un avance diagnóstico en cáncerde próstata. El objetivo es demostrar que los resultados enequipos de 1,5-Tesla no son inferiores a los equipos de 3-Tesla para el correcto diagnóstico de cáncer de próstata.Material y métodos: Estudio transversal comparativo de no inferioridad entre resultados de biopsia fusión.344 pacientes con sospecha de cáncer de próstata (PSA elevado y/o tacto rectal sospechoso) y RMmp interpretada ycomprobada por los mismos radiólogos en todos los casos,270 con 1,5-Tesla y 74 con 3-Tesla, con al menos una imagen PIRADSv2≥ 3. Criterios de exclusión: biopsia positiva o tratamiento prostático previo. Consideramos malignidad como ISUP≥ 1 y tumor significativo como ISUP≥ 2.Comparamos medidas de tendencia central (test Wilcoxony t-student), prevalencias e IC95% (Chi2 y prueba-Z) y testde prueba diagnóstica (gold estándar: ISUP de biopsia dirigida) según RMmp empleado.Resultados: Medianas de volumen prostático50cc(IQR:33,5) y PSA 6,11ng/ml(IQR:3,39). La mediade edad fue 67,4±8,1años. El número de lesiones sospechosas/paciente fue 1,3 (1,5-Tesla) y 1,5 (3-Tesla). No encontramos diferencias entre RMmp (muestras homogéneasy comparables). 57%(1,5-Tesla) vs 66%(3-Tesla) biopsiasdirigidas presentaron malignidad, y 34%vs38% tumorsignificativo, sin diferencias significativas. Se, Sp, VPP yVPN para malignidad (1,5-Tesla vs 3-Tesla) de 96%vs90%,38%vs44%, 67%vs76%, y 86%vs69%, sin diferenciassignificativas.Conclusiones: No encontramos diferencias significativas entre RMmp de 1,5-Tesla y 3-Tesla respecto a los resultados de biopsia. No disponer de RMmp de 3-Tesla...(AU)

Renal cell carcinoma with vascular invasion: Mortality and prognostic factors. / Carcinoma de células renales con invasión vascular: mortalidad y factores pronósticos.

OBJECTIVE: Analysis of the results of patients who had been operated of renal cell carcinoma with vascular invasion in our institution, evaluation of prognostic factors and complications. METHODS: Retrospective observational study of 37 patients diagnosed of renal cell carcinoma with vascular invasion operated between May 1999 and July 2013. We used the method of Kaplan-Meier survival analysis and the Mantel-Haenszel's test (log rank) and the Cox's proportional hazards analysis test to analyse the risk factors of mortality. RESULTS: The median age was 60 years. Mean follow-up period was 42.1 months. The median overall survival and disease-free survival were 53.8and 36.3 months, respectively. There was statistical association between overall survival and ASA (p=0.047), tumor stage (p=0.003), lymph node involvement (p=0.024), presence of metastases (p=0.013), level of tumor thrombus (p=0, 05) and histological type (p=0.001). 14 patients had grade IIIb complications or higher according to the Clavien Dindo classification, the most frequent was bleeding. CONCLUSIONS: Renal cell carcinoma with vascular invasion is a disease with high rate of mortality. Surgery is a therapeutic option that can be curative. The number of complications is important. Survival is conditioned by the ASA, tumor stage, the level of tumor thrombus, lymph node involvement, metastasis and histological type.

Dengue y leptospirosis compartiendo el mismo nicho ecológico en la localidad ribereña de Carmen del Paraná (Itapúa) / Dengue and leptospirosis share the same ecological niche in Carmen del Paraná (Itapua), a riverside locality

Para conocer la prevalencia de dengue y leptospirosis en pobladores de Carmen del Paraná (Itapúa) realizamos un estudio transversal descriptivo. Aplicamos un cuestionario y toma de muestras sanguíneas, mediante un muestreo por hogares. Los jefes de familia fueron informados sobre la metodología, beneficios, posibles riesgos a fin de decidir su participación o de sus familiares en el estudio. Por el método de ELISA determinamos la presencia de anticuerpos IgG anti-leptospira en 211 mujeres y 107 varones, contra el virus del dengue en 255 mujeres y 142 varones. Hallamos una seroprevalencia de dengue de 25% (IC 95%:20,7-29,4), no habiendo diferencia entre varones y mujeres. La prevalencia de leptospirosis fue de 24,1% (IC95%:19,6-29,2), siendo mayor en mujeres que en varones (28,4% vs 15,9%; p <0,05). La seroprevalencia de dengue fue más alta en los mayores de 35 años (36% vs 17%, p<0,001), mientras que la leptospirosis lo fue en menores de 15 años (48% vs 21,6%, p<0,001). El 8% de los individuos tenía serología positiva tanto para leptospira como para dengue. En esta comunidad, un importante número de individuos tiene riesgo de desarrollar dengue hemorrágico. La coexistencia de dengue y leptospirosis en el mismo nicho ecológico es importante porqueal presentar características clínicas semejantes, implican un problema para el médico al momento de establecer el diagnóstico oportuno y el tratamiento apropiado, entonces sería importante el desarrollo de estrategias integrales de vigilancia epidemiológica, prevención y control de estas enfermedades que se basen en la participación conjunta del personal de salud, autoridades y comunidad.

This cross-sectional descriptive study was carried out to know the prevalence of dengue and leptospirosis in the inhabitants of Carmen del Paraná (Itapúa). Through a house hold sampling, we applied a questionnaire and collected blood samples. The heads of the families were informed about the methodology, benefits and possible risks so that they could decide about the participation of their families in the study. The presence of anti-leptospira IgG antibodies was determined by ELISA method in 320 individuals (211women and 107 men) and anti-dengue virus antibodies in 399 individuals (255 women and 142 men). We found a dengue virus seroprevalence 25% (IC 95 %:20.7-29.4) without any differences between men and women. The prevalence of leptospirosis was24.1% (IC95 %:19.6-29.2), higher in women than in men (28.4 % vs. 15.9 %; p value <0.05). Dengue seroprevalence was higher in the age group older than 35 years old(36% vs. 17%, value of p <0.001), where as leptospirosis was more prevalent in those younger than 15 years old (48% vs 21.6%, p value <0.001). Eight percent of the individuals who were leptospira positive were also dengue positive. In this community, there is an important number of individuals who has a risk of developing hemorrhagicdengue. The coexistence of dengue and leptospirosis in the same ecological niche is important because both diseases presented similar clinical characteristics, implying a problem for the physician at the time of determining the appropriate diagnosis andtreatment. Therefore, it would be important to develop integral strategies of epidemiological surveillance, prevention and control of these diseases, based on the jointparticipation of healthcare personnel, authorities and community.

Riesgo de adquirir ITS/SIDA en niños de barrios marginales de Asunción, Paraguay / Risk of acquiring STD/AIDS in children of slums of Asunción, Paraguay

La diseminación de las infecciones de transmisión sexual/síndrome de inmunodeficiencia adquirida(ITS/SIDA) se presenta principalmente en jóvenes, con una tendencia creciente a la asociación conpobreza y falta de acceso a educación y salud pública. El objetivo del estudio fue explorar lasituación de riesgo y el conocimiento sobre el VIH/SIDA en niños de 9-15 años que asistían a loscolegios del Barrio Santa Ana y Ricardo Brugada. El consentimiento para el estudio fue solicitado alas autoridades del colegio y a los padres. Se les aplicó un cuestionario administrado por unaencuestadora, que incluía el nivel de conocimientos sobre los factores de riesgo, sobre las formasde prevención para la infección por VIH. Un total de 297 niños participaron en el estudio, 173(58%) de sexo femenino, la mayoría (86%) vivían en condiciones de hacinamiento. Del 28 % quetrabajaban, 66% de los varones eran vendedores ambulantes y el 49 % de las niñas eranempleadas domésticas. El 80 % no conocía las formas de transmisión del ITS/SIDA, ni que elpreservativo puede prevenir la transmisión. El 9% (11/24) de los varones y el 2% (3/173) de lasniñas tuvieron relaciones sexuales. El 10% refieren abusos sexuales. El 25% ingieren bebidasalcohólicas, el 2% consume drogas inhalantes. En conclusión, este estudio muestra un importantedesconocimiento sobre las ITS/SIDA, formas de prevenirlas, la falta de percepción de riesgo concondiciones ambientales y socioeconómicas que la favorecen. Estos resultados plantean la urgentenecesidad de iniciar campañas de prevención en este grupo

Hernia de Richter como causa de obstrucción del intestino delgado / Richter's hernia presenting as small bowel obstruction

El objetivo del trabajo es presentar 4 casos de hernia de Richter que ocasionan problemas mecánicos intestinales, concretamente oclusión del intestino delgado. En todos los casos hubo un grave deterioro del estado general y una deshidratación importante, siendo el cuadro clínico lentamente progresivo con una sintomatología en varios casos de distensión abdominal y en otro caso de diarrea persistente. La demora en su diagnóstico ocasiona una cirugía tardía, con un aumento de la morbimortalidad, por lo que creemos que el adecuado conocimiento de esta rara enfermedad quirúrgica es importante (AU)

Arundifungin, a novel antifungal compound produced by fungi: biological activity and taxonomy of the producing organisms.

Echinocandins, the lipopeptide class of glucan synthase inhibitors, are an alternative to ergosterol-synthesis inhibitors to treat candidiasis and aspergillosis. Their oral absorption, however, is low and they can only be used parenterally. During a natural product screening program for novel types of glucan synthesis inhibitors with improved bioavailability, a fungal extract was found that inhibited the growth of both a wild-type Saccharomyces cerevisiae strain and the null mutant of the FKS1 gene (fks1::HIS). The mutant strain was more sensitive to growth inhibition, suggesting that the fungal extract could contain an inhibitor of glucan synthesis. A novel acidic steroid, named arundifungin, was purified from a fungal extract obtained from a liquid culture of Arthrinium arundinis collected in Costa Rica. Arundifungin caused the same pattern of hallmark morphological alterations in Aspergillus fumigatus hyphae as echinocandins, further supporting the idea that arundifungin belongs to a new class of glucan synthesis inhibitors. Moreover, its antifungal spectrum was comparable to those of echinocandins and papulacandins, preferentially inhibiting the growth of Candida and Aspergillus strains, with very poor activity against Cryptococcus. Arundifungin was also detected in nine other fungal isolates which were ecologically and taxonomically unrelated, as assessed by sequencing of the ITS1 region. Further, it was also found in two more Arthrinium spp from tropical and temperate regions, in five psychrotolerant conspecific isolates collected on Macquarie Island (South Pacific) and belonging to the Leotiales, and in two endophytes collected in central Spain (a sterile fungus belonging to the Leotiales and an undetermined coelomycete).

Screening of basidiomycetes for antimicrobial activities.

As a part of a screening programme developed to evaluate the antimicrobial activity of basidiomycetes, 317 isolates representing 204 species collected in Spain were screened against a range of human clinical pathogens and laboratory controls. Extracts from 45% of the isolates, representing 109 species, showed antimicrobial activity. Antibacterial activity was more pronounced than antifungal activity. The proportion of extracts from basidiomycetes showing antimicrobial activity was similar to or above that obtained for representative orders of Ascomycetes, such as Pezizales and Xylariales, but lower than that produced by members of the orders Diaporthales, Eurotiales, Hypocreales, Leotiales and Sordariales. Suprageneric taxa (orders and families) did not show pronounced differences in their antimicrobial activities though such differences were observed at the genus level, suggesting that the ability to produce these bioactive compounds is not homogenously distributed amongst the basidiomycetes. Isolates from some species showed large differences in their ability to produce metabolites with antimicrobial activity, possibly reflecting genetic differences at the infraspecific level.

Inhibition of fungal sphingolipid biosynthesis by rustmicin, galbonolide B and their new 21-hydroxy analogs.

The mode of action of the known antifungal macrolides rustmicin (1) and galbonolide B (2) has been determined to be the inhibition of sphingolipid biosynthesis. A large scale fermentation and isolation process was developed for production of large quantities of rustmicin. New 21-hydroxy derivatives of both compounds were isolated from pilot scale fermentations and were also produced by biotransformation of rustmicin and galbonolide B.

The discovery of australifungin, a novel inhibitor of sphinganine N-acyltransferase from Sporormiella australis. Producing organism, fermentation, isolation, and biological activity.

Potent antifungal activity was detected in fermentation extracts of Sporormiella australis and two related components were isolated from solid fermentations using silica gel and high speed countercurrent chromatography. The most active antifungal component, australifungin, contained a unique combination of alpha-diketone and beta-ketoaldehyde functional groups. Australifungin exhibited broad spectrum antifungal activity against human pathogenic fungi with MICs against Candida spp., Cryptococcus neoformans, and Aspergillus spp. between 0.015 and 1.0 microgram/ml. Mode of action studies revealed that australifungin interfered with fungal lipid metabolism by specifically inhibiting sphingolipid synthesis at the step converting sphinganine to ceramide.

Inhibition of gluconeogenesis by tolbutamide in isolated rat hepatocytes: modulation of glucose-6-phosphate substrate cycle.

In hepatocytes isolated from 24-hour fasted rats, the oral hypoglycemic agent tolbutamide (1 mmol/L) inhibited glucose formation from different concentrations (1 to 20 mmol/L) of galactose, dihydroxyacetone, glycerol, and a mixture of L-lactate:pyruvate (molar ratio, 10:1). Parallel to the reduction of gluconeogenesis, tolbutamide stimulated L-lactate formation when cells were incubated with either galactose, dihydroxyacetone, or glycerol. All these tolbutamide effects occurred without significant modification of hepatocyte fructose-2,6-bisphosphate (F-2,6-P2) levels. Only when glucose was included in the incubation medium was the inhibition of gluconeogenesis caused by the sulfonylurea accompanied by a significant increment of the cellular F-2,6-P2 concentration. Under these conditions, tolbutamide potentiated the effect of glucose in promoting the increase of this regulatory metabolite, as well as the stimulation of glycolysis; in addition, tolbutamide increased the cellular pool of hexose-6-phosphates and the rate of tritium release from (2-3H)glucose. These results support the hypothesis that tolbutamide regulates hepatic glucose metabolism, at least, by modulating the glucose-6-phosphate substrate cycle.

Effect of adrenalectomy and glucocorticoid treatment on the levels of an insulin-sensitive glycosyl-phosphatidylinositol in isolated rat hepatocytes.

Insulin resistance caused by dexamethasone administration to rats was accompanied by a marked decrease in the hepatocyte content of an insulin-sensitive glycosyl-phosphatidylinositol, as well as by a blockade of its hydrolysis in response to this hormone. In contrast, bilateral adrenalectomy provoked a significant increase of the cellular glycosyl-phosphatidylinositol levels. Under all the assayed metabolic conditions, a close direct correlation was established between the basal content of this compound and the number of insulin receptors present in the isolated hepatocytes.

Tolbutamide enhances insulin action on gluconeogenesis and on fructose 2,6-bisphosphate levels in isolated rat hepatocytes.

In hepatocytes isolated from fed rats and incubated either under basal conditions or in the presence of glucagon, tolbutamide reduced gluconeogenesis from (U-14C) pyruvate by increasing the cellular concentration of fructose 2,6-bisphosphate. Furthermore, this sulfonylurea enhanced the inhibitory action of insulin on glucagon-stimulated gluconeogenesis; this effect was accompanied by a more marked increase of the cellular concentration of fructose 2,6-bisphosphate than that elicited by either insulin or the sulfonylurea alone. In connection with this, tolbutamide--without significant modification of cellular cyclic AMP levels--raised the proportion of 6-phosphofructo 2-kinase in active form in hepatocytes incubated either under basal conditions or in the presence of glucagon, and reinforced the action of insulin in antagonizing the glucagon-mediated inactivation of this enzyme.

A phospho-oligosaccharide mimics insulin action on glycogen phosphorylase and pyruvate kinase activities in isolated rat hepatocytes.

A phospho-oligosaccharide which is the polar head group of a novel insulin-sensitive glycophospholipid has recently been involved in insulin action. We have investigated the insulin-like effects of this phospho-oligosaccharide on both glycogen phosphorylase a and pyruvate kinase activities of hepatocytes incubated in the presence of glucagon (0.1 nM). Similarly to insulin, the phospho-oligosaccharide antagonized glucagon-dependent activation of glycogen phosphorylase, as well as the inactivation of pyruvate kinase caused by this hormone. The antagonistic action of the phospho-oligosaccharide on glucagon effects was dose-dependent. Furthermore, it partially antagonized glucagon-stimulated cyclic AMP levels. These results support the hypothesis that this phospho-oligosaccharide mediates at least some insulin actions in hepatocytes.

Effect of glipizide on hepatic fructose 2,6-bisphosphate concentration and glucose metabolism.

Glipizide raised, in a dose-dependent manner, the concentration of fructose 2,6-bisphosphate in hepatocytes isolated from 24-hour fasted rats and incubated in the presence of 10 mmol/L glucose. Simultaneously, the rate of L-lactate production, as well as the rate of 3H2O formation from (3-3H)glucose, increased markedly. The concentration of glipizide calculated as corresponding to the half-maximal effect in these metabolic parameters was 12 to 15 mumol/L. In hepatocytes isolated from fed rats, either normal or made diabetic by treatment with alloxan, glipizide inhibited the conversion of both (U-14C)pyruvate and (U-14C)lactate to (14C)glucose; an inverse correlation was established between hepatocyte fructose 2,6-bisphosphate levels and the rate of gluconeogenesis. The increase of fructose 2,6-bisphosphate concentration elicited by glipizide, which occurs without a significant modification of either 6-phospho-fructo 2-kinase activity or hepatocyte cyclic AMP levels, seems to be related to a significant accumulation of hexose 6-phosphates (glucose 6-phosphate and fructose 6-phosphate) in the hepatic cells.

Chlorpropamide raises fructose-2,6-bisphosphate concentration and inhibits gluconeogenesis in isolated rat hepatocytes.

The addition of chlorpropamide to hepatocytes isolated from fed rats raised the cellular concentration of fructose-2,6-bisphosphate (F-2,6-P2), a regulatory metabolite that plays a relevant role in the control of hepatic glucose metabolism. The effect of chlorpropamide was dose dependent; a statistically significant increase was already seen at 0.2 mM of the sulfonylurea. The accumulation of F-2,6-P2 caused by chlorpropamide (1 mM) was parallel to the stimulation of L-lactate production (36.6 +/- 4.8 versus 26.1 +/- 2.6 mumol of lactate/g of cells X 20 min; N = 5, P less than 0.05) and to the inhibition of gluconeogenesis (0.57 +/- 0.1 versus 0.94 +/- 0.09 mumol of [U-14C]pyruvate converted to glucose/g of cells X 20 min; N = 5, P less than 0.05). In addition, chlorpropamide enhanced the inhibitory action evoked by insulin on glucagon-stimulated gluconeogenesis. This combined effect of chlorpropamide and insulin seems to be correlated with the synergistic accumulation of F-2,6-P2 provoked by the simultaneous action of these two agents on glucagon-treated hepatocytes. Finally, neither 6-phosphofructo-2-kinase activity nor hepatocyte cyclic AMP levels were significantly changed by the presence of the sulfonylurea in the incubation medium. Our results support the concept that chlorpropamide, by a cyclic AMP-independent mechanism, increases the hepatic content of F-2,6-P2 and, in this way, enhances the glycolytic flux and inhibits glucose output by the liver.