Evolución de las características del paciente candidato a prostatectomía radical y de los resultados obtenidos con la técnica / Evolution of the patient characteristics of candidates for radical prostatectomy and the results obtained with the technique

Objetivos: Evaluar el perfil oncológico y el riesgo de recidiva bioquímica de pacientes con cáncer de próstata sometidos a prostatectomía radical en función del periodo en el que fueron intervenidos. Evaluar las diferencias en el PSA al diagnóstico de los pacientes con o sin recidiva bioquímica en función de dichos periodos. Material y métodos: Diseño observacional hacia delante de una cohorte de 972 prostatectomías radicales realizadas en 3 periodos (1994-2000, 2001-2006, 2007-2011). La importancia del PSA al diagnóstico en los periodos y en la recidiva bioquímica se evaluó mediante modelo lineal generalizado. El comportamiento predictivo independiente de recidiva bioquímica se analizó mediante regresión de Cox. Resultados: La mediana de seguimiento fue de 38 (16-76) meses. El PSA diagnóstico fue más alto en el periodo 1994-2000 (12,97 ng/ml, p < 0,001). Un 72% de los pacientes del periodo 2007-2011 frente al 55% de los del periodo 1994-2000 se diagnosticaron con estadio clínico T1c (p < 0,001). El porcentaje de extensión extracapsular en la pieza disminuyó del 27 al 18% del periodo 1994-2000 al periodo 2007-2011 (p < 0,001). El porcentaje de pacientes con recidiva bioquímica pasó del 38 al 14% del primer al tercer periodo (p > 0,001). La diferencia entre el PSA al diagnóstico de los pacientes con o sin recidiva bioquímica fue independiente del periodo (p = 0,84). El periodo en que se realiza la cirugía no es un factor predictivo independiente de recidiva bioquímica (p = 0,09). Conclusiones: Los pacientes del periodo 2007-2011 presentan menos enfermedad extracapsular en la prostatectomía radical. El periodo no es un factor predictivo independiente de recidiva bioquímica

Objectives: To evaluate the oncological profile and risk of biochemical recurrence of patients with prostate cancer who underwent radical prostatectomy based on the time period in which the patients were operated. To evaluate the differences in prostate-specific antigen (PSA) at diagnosis of patients with or without biochemical recurrence based on these time periods. Material and methods: Observation carried forward study of a cohort of 972 radical prostatectomies performed during 3 time periods (1994-2000, 2001-2006, 2007-2011). The importance of PSA at diagnosis on the time periods and on biochemical recurrence was assessed using a generalized linear model. The independent predictive behavior of biochemical recurrence was analyzed using Cox regression. Results: The median follow-up was 38 (16-76) months. PSA levels at diagnosis were higher in the period 1994-2000 (12.97 ng/mL, P < .001). Seventy-two percent of the patients from the period 2007-2011 were diagnosed as clinical stage T1c (P < .001), compared with 55% from the period 1994-2000. The percentage of extracapsular extension in the specimen decreased from 27% to 18% from the period 1994-2000 to the period 2007-2011 (p<.001). The percentage of patients with biochemical recurrence went from 38% to 14% from the first to the third period (P > .001). The difference between PSA levels at diagnosis for the patients with or without biochemical recurrence was independent of the period (P = .84). The period during which surgery was performed was not an independent predictive factor for biochemical recurrence (P = .09). Conclusions: Patients from the 2007-2011 period had less extracapsular disease in the radical prostatectomy. The period was not an independent predictive factor for biochemical recurrence

Evolution of the patient characteristics of candidates for radical prostatectomy and the results obtained with the technique.

OBJECTIVES: To evaluate the oncological profile and risk of biochemical recurrence of patients with prostate cancer who underwent radical prostatectomy based on the time period in which the patients were operated. To evaluate the differences in prostate-specific antigen (PSA) at diagnosis of patients with or without biochemical recurrence based on these time periods. MATERIAL AND METHODS: Observation carried forward study of a cohort of 972 radical prostatectomies performed during 3 time periods (1994-2000, 2001-2006, 2007-2011). The importance of PSA at diagnosis on the time periods and on biochemical recurrence was assessed using a generalized linear model. The independent predictive behavior of biochemical recurrence was analyzed using Cox regression. RESULTS: The median follow-up was 38 (16-76) months. PSA levels at diagnosis were higher in the period 1994-2000 (12.97ng/mL, P<.001). Seventy-two percent of the patients from the period 2007-2011 were diagnosed as clinical stage T1c (P<.001), compared with 55% from the period 1994-2000. The percentage of extracapsular extension in the specimen decreased from 27% to 18% from the period 1994-2000 to the period 2007-2011 (p<.001). The percentage of patients with biochemical recurrence went from 38% to 14% from the first to the third period (P>.001). The difference between PSA levels at diagnosis for the patients with or without biochemical recurrence was independent of the period (P=.84). The period during which surgery was performed was not an independent predictive factor for biochemical recurrence (P=.09). CONCLUSIONS: Patients from the 2007-2011 period had less extracapsular disease in the radical prostatectomy. The period was not an independent predictive factor for biochemical recurrence.

[Alterations in nocturnal melatonin secretion in patients with optic neuropathies]. / Alteraciones de la secreción nocturna de melatonina y neuropatías ópticas.

OBJECTIVE: To study nocturnal melatonin suppression induced by exposure to light in patients with bilateral optic neuropathies. METHODS: Observational, prospective case control study. Twenty patients were included in this study and distributed in 3 groups: Group A (n=5, Healthy Control Subjects), Group B (n=10, Experimental Patients) and Group C (n=5, Blind Control Subjects). LogMAR best-corrected visual acuity, standard automated perimetry mean deviation, retinal nerve fiber layer thickness by Optical Coherence Tomography and multifocal electroretinograpy (mfERG) were used to evaluate the changes. Melatonin was analysed in the saliva by radioimmunoassay after exposure to light (600 lux for 1 hour) (nocturnal melatonin suppression test). RESULTS: Statistically significant differences between the groups were found. No changes in the mfERG results were detected. The nocturnal melatonin suppression test was positive in all cases in Group A, 50% in Group B and none in Group C. CONCLUSIONS: Half of the patients with optic neuropathies and severe visual loss were shown to suffer significant melatonin regulation anomalies, probably due to the dysfunction of the intrinsically photosensitive retinal ganglion cells (ipRGC).

Alteraciones de la secreción nocturna de melatonina y neuropatías ópticas / Alterations in nocturnal melatonin levels in patiens wiht optic neuropathies

Objetivo: Evaluar la supresión de la secreción nocturnade melatonina inducida por exposición a laluz en pacientes con neuropatías ópticas bilaterales.Métodos: Estudio clínico de casos controles, observacionaly prospectivo. Tamaño muestral de 20pacientes distribuidos en 3 grupos: Grupo A (n=5,Sujetos Sanos Controles), Grupo B (n=10, PacientesExperimentales) y Grupo C (n=5, Sujetos ControlesCiegos). Se analiza la mejor agudeza visualcorregida LogMAR, la desviación media en perimetríaestática automatizada, el espesor medio de lacapa de fibras nerviosas retinianas mediante Tomografíade Coherencia Óptica y los registros de electrorretinografíamultifocal (mfERG). Se realizandeterminaciones de melatonina en saliva porradioinmunoensayo tras exposición a una luz de600 lux durante 1 hora (Test de supresión nocturnade melatonina).Resultados: Se encontraron diferencias estadísticamentesignificativas entre los grupos. No se observaroncambios en los registros de mfERG. El test de supresión nocturna de melatonina fue positivo entodos los casos del Grupo A, en el 50% de los casosdel Grupo B y en todos los casos del Grupo C fuenegativo.Conclusiones: El 50% de los pacientes con neuropatíasópticas y pérdida visual severa exhiben alteracionessignificativas en la secreción nocturna demelatonina, probablemente debido a una disfunciónde las células ganglionares de la retina intrínsecamentefotosensibles (ipCGR) (AU)

Objective: To study nocturnal melatonin suppressioninduced by exposure to light in patients withbilateral optic neuropathies.Methods: Observational, prospective case controlstudy. Twenty patients were included in this studyand distributed in 3 groups: Group A (n=5, HealthyControl Subjects), Group B (n=10, ExperimentalPatients) and Group C (n=5, Blind Control Subjects).LogMAR best-corrected visual acuity, standardautomated perimetry mean deviation, retinalnerve fiber layer thickness by Optical CoherenceTomography and multifocal electroretinograpy(mfERG) were used to evaluate the changes. Melatoninwas analysed in the saliva by radioimmunoassayafter exposure to light (600 lux for 1 hour) (nocturnalmelatonin suppression test).Results: Statistically significant differences betweenthe groups were found. No changes in themfERG results were detected. The nocturnal melatoninsuppression test was positive in all cases inGroup A, 50 % in Group B and none in Group C. Conclusions: Half of the patients with optic neuropathiesand severe visual loss were shown to suffersignificant melatonin regulation anomalies, probablydue to the dysfunction of the intrinsicallyphotosensitive retinal ganglion cells(A)

Cribado neonatal selectivo de anemia de células falciformes / Selective neonatal screening for sickle cell disease

No disponible

The peptidase inhibitor CGS-26303 increases endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1.

BACKGROUND AND PURPOSE: CGS-26303 inhibits endothelin converting enzyme (ECE)-1 more specifically than phosphoramidon. We have studied the effect of CGS-26303 on ECE-1 expression in bovine aortic endothelial cells. METHODS: ECE-1 activity and big endothelin (ET)-1 levels were measured by ELISA, ECE-1 expression using western and northern blot and promoter activity using transfection assays. KEY RESULTS: ECE-1 activity was completely inhibited by CGS-26303 25 microM and phosphoramidon 100 microM. CGS-26303 and phosphoramidon, though not thiorphan, a neutral endopeptidase (NEP) inhibitor, stimulated ECE-1 expression in cells (maximal effect at 16 h, 25 microM). Cycloheximide abolished that effect. CGS-26303 induced ECE-1 mRNA expression and ECE-1 promoter activity. CGS-35066, a selective ECE-1 inhibitor, mimicked the effects of CGS-26303, suggesting that the effect was specific to ECE-1 inhibition. Big ET-1 accumulated in the cells and in the supernatants after CGS-26303 treatment. Neither exogenously added ET-1 nor the blockade of their receptors with bosentan modified ECE-1 protein. When big ET-1 was added to cells, significant increases in ECE-1 protein content and ECE-1 promoter activity were found. Bosentan did not block those effects. CGS-26303 did not modify prepro-ET-1 expression. CGS-26303 and big ET-1 induced the same effects in human endothelial cells, at lower doses. CONCLUSIONS: These results suggest that the accumulation of big ET-1 is responsible for the effects of CGS-26303 on ECE-1 and they did not depend on NEP blockade. Changes in ECE-1 protein after the administration of CGS-26303 could lead to a decreased response in long-term treatments.

Troponina I y su valor pronóstico en las complicaciones posinfarto / Troponin I and prognostic value in post-acute myocardial infarction complications

ObjetivoDemostrar que los pacientes con dolor torácico que tienen elevada la troponina I en las primeras 12 horas se mueren más o sufren más complicaciones al cabo de nueve meses. Secundario: valorar la eficacia diagnóstica de la cTnI en el infarto de miocardio. Diseño Entre junio y agosto del 2003 se determinó cTnI, CK, CKMB, ECG a pacientes que acudieron al servicio de urgencias del hospital con sospecha de infarto (diseño transversal). También se observó la aparición de complicaciones (muerte por causa cardiovascular; angina, insuficiencia cardiaca y la aparición de reinfarto) durante los nueve meses siguientes (diseño observacional hacia delante). Participantes 167 pacientes que acudieron de forma consecutiva al servicio de urgencias del hospital con dolor torácico sospechoso de infarto. Resultados Se ha encontrado asociación entre los marcadores y las complicaciones con un riesgo relativo de 1,9(1,02-3,56) para un punto de corte de Troponina I =0,6 ng/ml, no encontrándose para los respectivos puntos de corte de la CK y CKMB. La Troponina I presentó una sensibilidad = 0,95 (0,55-0,99), siendo superior a la encontrada con los otros marcadores, con un valor predictivo negativo de 0,96 (0,83-0,98) y un cociente de probabilidad negativo de 0,08 (0,06-0,30). En cambio, la especificidad de la Troponina fuede 0,72 (0,48-0,72), menor que para la CK y CKMB. Conclusiones La troponina I es un buen predictor de las complicaciones (y no la CK y CKMB) y posee elevada eficacia para descartar un infarto, destacando una elevada sensibilidad, valor predictivo y cociente de probabilidad negativos

Objective Our main objective was to know if high Troponin I concentration during the first 12 hours in patients with chest pain has an increased risk over the 9 months post-acute myocardial infarction complications and, additionally to show the diagnostic efficacy of serum Troponin I measurement on chest pain patients. Design The diagnostic efficacy was evaluated by a cross sectional design and the incidence of complications (cardiovascular death, angina pectoris, cadiac insufficiency and re-infarct)over the next 9 months by a forward observational design. Serum Troponin, CKand CKMB were measured in a Dimension RXL(Dade). Participants 167 consecutive patients with chest pain attending to the Emergency Room of our Hospital over June, July and August in 2003. Results It was found assotiation between serum Troponin I and complications. The Troponin (cut off: 0.6ng/ml) relative risk was 1.9 (1.02-3.56) but it was found no association for the usual CK and CKMB cut-offs. The sensitivity of Troponin I was 0.95(0.55-0.99), higher than the sensitivity of the other markers. The Troponin negative predictive value was 0.96 (0.83-0.98) and the negative likelihood ratio was 0.08 (0.06-0.30). By contrast, the Troponin specificity was 0.72 (0.48-0.72), less than that of CK and CKMB. Conclusions Troponin I results show that this marker is a good predictor of complications, as a statistically significant association with the 9 months post infarct outcomes was found, and not CK and CKMB. Additionally, serum Troponin measurement shows a high efficacy to rule out a myocardial infarct, emphasizing a high sensitivity and negative predictive value

[Effect of lipoprotein (a) on the risk of coronary heart disease in adults aged less than 65 years in function of gender differences]. / Efecto de la lipoproteína (a) en el riesgo de enfermedad coronaria en adultos menores de 65 años en función del sexo.

BACKGROUND: Lipoprotein (a) is an independent risk factor for coronary heart disease, particularly the premature form. However, differences in its effect have been observed between men and women and in different populations. SUBJECTS AND METHODS: Lipid and non-lipid risk factors were compared (univariate and multivariate analyses) between a group of patients with myocardial infarction aged less than 65 years (n = 33) and those in their siblings (n = 32) and an unrelated healthy control group (n = 45) of the same gender. RESULTS: No differences were observed between male patients and their siblings. Differences were indeed observed when patients when compared with controls regarding HDL cholesterol (p = 0.001) and lipoprotein(a) (p = 0.002) serum concentrations. Female patients also had lower serum concentrations of HDL cholesterol than their siblings and controls, but non significant differences were observed for lipoprotein (a). The analysis of lipoprotein (a), categorized with respect to the 90th percentile of controls for each gender, showed a significant association with coronary heart disease only for males: crude odds ratio (OR) compared with controls 10.7 (95% CI: 2.1-54.9) and adjusted of 9.9 (95% CI: 1.6-60.7). The strength of this association was smaller and non-significant in women: crude OR 6,4 (95% CI: 0.8-51.8) and adjusted of 3.09 (95% CI: 0.3-47.2). CONCLUSIONS: Lipoprotein (a) concentrations are similar in siblings and increased concentrations in our population are more strongly and clearly association with coronary heart disease in men.

Efecto de la lipoproteína (a) en el riesgo de enfermedad coronaria en adultos menores de 65 años en función del sexo / Effect of lipoprotein (a) on the risk of coronary heart disease in adults aged less than 65 years. Gender differences

Fundamento. La lipoproteína (a) es un factor de riesgo independiente de enfermedad coronaria, sobre todo prematura; sin embargo, se han encontrado diferencias en su efecto entre varones y mujeres y en distintas poblaciones. Sujetos y métodos. Se comparan (análisis univariante y multivariante) los factores de riesgo lipídicos y no lipídicos de un grupo de pacientes con infarto de miocardio menores de 65 años (n = 33) con los de sus hermanos (n = 32) y un grupo de controles sanos no relacionados (n = 45) del mismo sexo. Resultados. No se han encontrado diferencias entre los pacientes varones y sus hermanos, pero sí al compararlos con los controles en cuanto a las concentraciones de colesterol HDL (p = 0,001) y las de lipoproteína (a) (p = 0,002). Las mujeres enfermas tuvieron también el colesterol HDL más bajo que sus hermanas y las controles, pero no mostraron diferencias significativas en la lipoproteína (a). El análisis de esta última, categorizada respecto al percentil 90 de los controles de su sexo, mostró una asociación significativa de su elevación con la enfermedad coronaria sólo en los varones: odds ratio (OR) crudo frente a los controles de 10,7 (IC 95 por ciento: 2,1-54,9) y ajustado de 9,9 (IC 95 por ciento: 1,6-60,7). En las mujeres la magnitud de esta asociación fue menor y no significativa: OR crudo de 6,4 (IC 95 por ciento: 0,8-51,8) y ajustado de 3,09 (IC 95 por ciento: 0,3-47,2). Conclusiones. Los valores de lipoproteína (a) son similares entre hermanos y en nuestra población su elevación se asocia con la enfermedad coronaria de una forma más clara e intensa en los varones (AU)

Prevention by tretinoin (all-trans-retinoic acid) of age-related renal changes.

The present work shows that dietary tretinoin (all-trans-retinoic acid) supplementation may be a useful manoeuvre for the prevention of age-related renal changes. 18-month-old male Fischer 344 rats fed during three months with standard chow plus tretinoin (1 mg/kg/day) did not exhibit any adverse effect in terms of bodyweight, urinary volume, renal handling of sodium and both hematological and blood chemistry parameters. Although the diet did not reduce age-related proteinuria nor renal lipid peroxidation, glomerular filtration rate and renal cortex protein content were, respectively, 30% higher and 30% lower than in age-matched control rats. These results suggest that dietary tretinoin supplementation may be a useful manoeuvre to slow the progression of age-related renal changes. Since glomerular H2O2 production increases during renal aging in rats, we studied the effect of tretinoin on the biology of cultured glomerular rat mesangial cells exposed to H2O2. Preincubation with tretinoin abolished cell proliferation or cell death induced, respectively, by low and high concentrations of H2O2. These results suggest that the modulation of the cellular actions of H2O2 may be relevant in the mechanisms through which tretinoin prevents age-related renal changes.

A possible role for platelet-activating factor in the hydrogen peroxide-induced TXB2 and PGE2 glomerular synthesis.

Hydrogen peroxide stimulates both prostanoid and platelet-activating factor (PAF) biosynthesis in cultured rat mesangial cells and isolated rat glomeruli. The present experiments were designed to try to establish some relationship between prostanoid and PAF synthesis in these renal structures, in the presence of hydrogen peroxide. Cells and glomeruli were incubated with hydrogen peroxide under different experimental conditions, and thromboxane B2 (TXB2), the stable metabolite of thromboxane A2 (TXA2), and prostaglandin E2 (PGE2) concentrations were measured in the supernatants of the cells or glomeruli. Moreover, H2O2-dependent PAF synthesis was measured by high performance liquid chromatography (HPLC) ([3H]acetate incorporation) and radioimmunoassay. H2O2 induced increased TXB2 and PGE2 production in cultured rat mesangial cells and isolated rat glomeruli. This effect was blocked by incubation in the presence of a PAF-receptor antagonist, BN-52021. This antagonist has no intrinsic effect either in basal prostanoid synthesis or in arachidonic acid-stimulated glomerular TXB2 synthesis. Alprazolam, another PAF antagonist, nonchemically related to BN-52021, also completely blocked the H2O2-induced production of TXB2 by isolated rat glomeruli. Moreover, H2O2 was also able to induce an increased [3H]acetate incorporation into a fraction comigrating with a PAF standard in HPLC in isolated glomeruli, and this effect was dependent on the H2O2 concentration tested. Moreover, H2O2 was also able to induce an increased [3H]acetate incorporation and increased synthesis of radioimmunoassayable PAF in cultured mesangial cells. These results suggest that the increased synthesis of PGE2 and TXB2 induced by H2O2 could be dependent on platelet-activating factor production.

[Diagnostic value of biliary acid serum levels in Gilbert syndrome]. / Valor de los ácidos biliares séricos en el diagnóstico del síndrome de Gilbert.

OBJECTIVE: The aim of the present work was to study the diagnostic value of the measurement of total serum bile acids in patients with Gilbert's syndrome as compared to the fasting test. PATIENTS AND METHODS: We have studied 17 patients, 12 males and 5 females, between the ages of 7 and 15 years. All patients showed a slight unconjugated hyperbilirubinemia (1.4 +/- 0.5 mg/dl) in the presence of repeated normal liver function test, including the total serum bile acids (7.47 +/- 2.3 mumol/l), and showed no evidence of hemolysis. A modified fasting test was performed in all of the patients. Serum bile acid levels (Merckotest, Merck Labs) and the biochemical parameters of liver function were determined before and after the fasting test. RESULTS: Our results show that to confirm the diagnosis of Gilbert's syndrome, the fasting test could be avoided in patients with increased unconjugated bilirubin levels if the basal levels of total serum bile acids are normal.

[Biological profile and value of determination of tartrate-resistant acid phosphatase in children]. / Perfil biológico y valor de la determinación de la fosfatasa ácida tartrato resistente en niños.

The serum level of tartrate-resistant acid phosphatase (TRAP) was measured in 130 children (61 M: 69 F). TRAP was found to be significantly higher in children under 5 years (n = 20) than in those aged between 5 and 9 years (n = 47) (8.3 + 2.4 vs 6.3 + 1.3 U/L, p less than 0.05). This last group had significantly lower TRAP levels than the one composed by children between 10 to 14 years (n = 60) (6.3 + 1.3 vs 7.5 + 1.2 U/L, p less than 0.02). We observed that a significant correlation existed between TRAP and alkiline phosphatase (r = 0.672, p less than 0.001). There was no correlation between TRAP and age and no difference between sexes. These results suggest that TRAP is useful as a marker of bone remolding in children.