Autophagy and mitochondrial alterations in human retinal pigment epithelial cells induced by ethanol: implications of 4-hydroxy-nonenal.

Retinal pigment epithelium has a crucial role in the physiology and pathophysiology of the retina due to its location and metabolism. Oxidative damage has been demonstrated as a pathogenic mechanism in several retinal diseases, and reactive oxygen species are certainly important by-products of ethanol (EtOH) metabolism. Autophagy has been shown to exert a protective effect in different cellular and animal models. Thus, in our model, EtOH treatment increases autophagy flux, in a concentration-dependent manner. Mitochondrial morphology seems to be clearly altered under EtOH exposure, leading to an apparent increase in mitochondrial fission. An increase in 2',7'-dichlorofluorescein fluorescence and accumulation of lipid peroxidation products, such as 4-hydroxy-nonenal (4-HNE), among others were confirmed. The characterization of these structures confirmed their nature as aggresomes. Hence, autophagy seems to have a cytoprotective role in ARPE-19 cells under EtOH damage, by degrading fragmented mitochondria and 4-HNE aggresomes. Herein, we describe the central implication of autophagy in human retinal pigment epithelial cells upon oxidative stress induced by EtOH, with possible implications for other conditions and diseases.

Is the cleft lift procedure for non-acute sacrococcygeal pilonidal disease a definitive treatment? Long-term outcomes in 74 patients.

PURPOSE: No definitive surgical treatment for non-acute pilonidal disease has been established thus far. We herein report the short-term and long-term outcomes of 74 consecutive patients who underwent the cleft lift procedure for non-acute pilonidal disease. METHODS: A total of 74 consecutive patients who underwent the cleft lift procedure for the treatment of non-acute pilonidal disease were evaluated. RESULTS: Complete healing was achieved in 54 patients (73%). Wound seroma was observed in 12 patients (15%) in the first week, and this persisted until the second week in 10 patients (13%). Partial dehiscence was found in eight patients (11%). One patient presented with complete wound dehiscence (1%), and another experienced early postoperative bleeding (1%). Wound infection was observed in one patient (1%). The median follow-up period was 51.5 months (range 15-88 months). Three cases of recurrences were observed, which occurred after 51, 42 and 12 months of follow-up. CONCLUSIONS: If longer-term follow-up is achieved, definitive conclusions may be obtained. However, the present results suggest that the cleft lift procedure may become the gold standard technique for the surgical management of non-acute pilonidal disease.

Efficacy of laparoscopic approach in the management of early liver transplant complications.

The use of the laparoscopic approach in managing early liver transplant complications has been shown to be safe and feasible in various settings with the advantages of shorter recovery period, decreased postoperative pain, and rapid functional recovery. The laparoscopic approach has been used to resolve postoperative complications in kidney and pancreas recipients and less often in orthotopic liver transplantation (OLT) recipients, most of them in the late period (> 1 month posttransplantation). We herein describe our experience with the laparoscopic management of early complications after liver transplantation. From May 2009 to May 2011, we successfully treated three patients with early abdominal complications after OLT using a laparoscopic approach. Three patients-two with intraabdominal bleedings and one with a small bowel obstruction were treated successfully, thereby avoiding risks of a relaparotomy. In addition to these benefits, the laparoscopic approach causes less tissue injury and consequently evokes a minor innate immune response.

Transthoracic oesophagectomy with lymphadenectomy in 100 oesophageal cancer patients: multidisciplinary approach.

OBJECTIVES Analysis of the results on the treatment of esophageal cancer by transthoracic esophagectomy by a multidisciplinary team of surgeons and oncologists. METHODS Between January 1990 and December 2009, 100 consecutive patients underwent transthoracic esophagectomy. Data were collected prospectively and clinical, pathological and histological features of the tumors were analyzed as well as the results of postoperative morbidity and mortality. RESULTS The average patient age was 55 years (range 31- 83 years). In 59 cases the tumor was located in the lower third and in 41 cases in the middle third. Forty-six patients had adenocarcinoma and 54 squamous cell carcinoma. In 54 cases radio-chemotherapy was planned preoperatively. Classifi cation according to pathological tumor stage was: stage 0 in 21 patients, stage I in 10 patients, stage IIa in 28, stage IIb in 9, stage III in 21 and stage IV in 11. The mean number of lymph nodes examined was 14 (range 0-28). Hospital mortality occurred in 4 cases and postoperative complications in 29 patients (33%). The most frequent postoperative complication was pulmonary complications in 17 cases. The average hospital stay was 15.2 days (range 10-40 days) CONCLUSIONS The results of esophageal cancer have been improved in recent years due to the formation of multidisciplinary teams in this pathology. In our study we have shown that the results obtained with the transthoracic technique for cancer of the esophagus are within the ranges reported in the literature for teams with high prevalence of the disease.

Transthoracic oesophagectomy with lymphadenectomy in 100 oesophageal cancer patients: multidisciplinary approach

OBJECTIVES Analysis of the results on the treatment of esophageal cancer by transthoracic esophagectomy by a multidisciplinary team of surgeons and oncologists. METHODS Between January 1990 and December 2009, 100 consecutive patients underwent transthoracic esophagectomy. Data were collected prospectively and clinical, pathological and histological features of the tumors were analyzed as well as the results of postoperative morbidity and mortality. RESULTS The average patient age was 55 years (range 31- 83 years). In 59 cases the tumor was located in the lower third and in 41 cases in the middle third. Forty-six patients had adenocarcinoma and 54 squamous cell carcinoma. In 54 cases radio-chemotherapy was planned preoperatively. Classifi cation according to pathological tumor stage was: stage 0 in 21 patients, stage I in 10 patients, stage IIa in 28, stage IIb in 9, stage III in 21 and stage IV in 11. The mean number of lymph nodes examined was 14 (range 0-28). Hospital mortality occurred in 4 cases and postoperative complications in 29 patients (33%). The most frequent postoperative complication was pulmonary complications in 17 cases. The average hospital stay was 15.2 days (range 10-40 days) CONCLUSIONS The results of esophageal cancer have been improved in recent years due to the formation of multidisciplinary teams in this pathology. In our study we have shown that the results obtained with the transthoracic technique for cancer of the esophagus are within the ranges reported in the literature for teams with high prevalence of the disease (AU)

Efectos de la aplicación del Kinesio taping(TM) en el diafragma en el resultado la cicloergoespirometría y la prueba marcha de 6 minutos / Effects of the application of kinesio taping on the diaphragm on the

El objetivo de este estudio es comprobar si la aplicación de técnica diafragmática anterior de Kinesio™ taping (KT) mejora el rendimiento deportivo de sujetos sanos.DiseñoPruebas repetidas, aleatorización en el orden de realización de las pruebas con o sin vendaje.Material y métodosLa muestra del estudio incluyó a 17 sujetos, con edades comprendidas entre los 21 y los 38 años, 10 varones y 7 mujeres. Se realizaron pruebas de cicloerogespirometría y de marcha de 6 minutos. Los sujetos fueron citados en dos días distintos, con una semana de diferencia, de forma que un día se realizaban las pruebas con KT y otro día sin el vendaje diafragmático. En primer lugar se calculó el peso muscular del sujeto por cineantropometría y bioimpedancia. En la cicloerogespirometría, se registraron valores de consumo máximo de oxígeno relativo al peso muscular. Los resultados de la prueba de marcha de 6 minutos marcha se expresaron como metros recorridos y trabajo realizado (metros por kg de masa muscular).ResultadosNo se observaron efectos significativos de la aplicación del KT. Se encontraron diferencias significativas en la prueba de marcha de 6 minutos marcha entre la primera y la segunda prueba, tanto en los metros recorridos (distancia 1.ª prueba=834,69±107,03 m; 2.ª prueba=891,12±93,91 m; p=0,007), como en el trabajo realizado considerando la masa magra medida mediante bioimpedancia eléctrica (p=0,008) o la masa muscular medida mediante cineantropometría (p=0,009).ConclusionesLa aplicación anterior de KT no tiene efecto en el resultado de la cicloergometría y prueba de marcha de 6 minutos. Se confirma el efecto de aprendizaje en la prueba de marcha de 6 minutos (AU)

Objective: The aim of the study was to verify whether the application of the anterior diaphragmatictechnique of KinesioTM taping (KT) improves the performance in sports in healthysubjects.Design: Repeated measures with randomization in order of tests, with or without KT.Material and methods: The study sample included 17 subjects, 10 men and 7 women, 21 to38 years old. A cycloergospirometric or graded exercise test (bike test with spirometry) and6 minute walk test were performed. The subjects came on two separate days, 7 days apart,performing the KT tests on one of the days and the tests without the KT on the other. In thefirst place, muscle weight was calculated through anthropometry and bioimpedance. Duringthe cycloergospirometric test, variables that included the maximal oxygen consumption per kgof muscle achieved on the graded exercise test were measured. The results analyzed from the6 minute walk test included distance covered and work performed (distance per kg of musclemass).Results: The KT did not produce any significant changes in the variables measured duringthe graded exercise test or the 6 minute walk test. A significant learning effect was observedonly for the 6 minute walking test results, both for the distance covered (Distance 1sttest = 834.69±107.03 m; 2nd test = 891.12±93.91 m; p = .007) and for the work achieved(P = .008).Conclusions: There was no significant effect of diaphragmatic KT on results of the gradedexercise test and 6 minute walk test. There is a learning effect for the 6 minute walk test (AU)

Solid pseudopapillary tumor of the pancreas (SPPT). Still an unsolved enigma.

Solid pseudo-papillary tumor (SPPT) is a rare cystic tumor of the pancreas (1-3% of exocrine tumors of the pancreas) which shows an "enigmatic" behavior on the clinical and molecular pattern. A retrospective analysis of the cytological studies and resected specimens of pancreatic cystic tumors from May 1996 to February 2010 was carried out. Three cases of SPPT were found, which are the objective of this study. The diagnosis was established upon occasional finding in the abdominal CT, in spite of sizing between 3 and 6 cm of diameter. In the three cases the preoperative diagnosis was confirmed by cytology and specific immunohistochemical staining. Cases 2 and 3 showed strong immunoreactivity for Beta-Catenin and E-Cadherin staining. Radical resection (R0) was carried out in the three cases. A young male -21 years of age (case 1)- who had duodenal infiltration and two lymph nodes metastases died of hepatic and peritoneal recurrence 20 months following surgery. The other two cases are free of disease. The current review of the literature reports roughly 800 cases since the first report in 1959, and shows the enigmatic character of this tumor regarding the cellular origin, molecular pathways, prognostic factors and clinical behavior.

Effect of physical fitness and endurance exercise on indirect biomarkers of recombinant erythropoietin misuse.

Erythropoietin (EPO) and soluble transferrin receptor (sTfR) in serum have been proposed as indirect biomarkers for the detection of recombinant human EPO (rhEPO) misuse in sport. The purpose of the present study was to investigate the influence of different levels of physical fitness, sport, different training workload during the sport season, and endurance exercise in the concentrations of these serum biomarkers for their application into mathematical models to indirectly detect rhEPO misuse. Serum EPO and sTfR concentrations were measured in 96 elite athletes of various sports along the sport season, in 21 recreational athletes at baseline (non exercising) conditions and in 129 other recreational athletes before and after long-distance races (10 and 21 km). In elite athletes, hemoglobin concentrations and percentage of reticulocytes were also measured, and indirect detection models applied. In recreational athletes, for EPO and sTfR, significant differences were only observed after the 21-km race. In baseline conditions, no differences were observed between recreational and elite athletes for EPO and sTfR. In elite athletes, individual EPO and sTfR concentrations slightly changed over the sport season, with coefficients of variation (CV) of 26.1 % and 9.0 %, respectively. Hemoglobin and reticulocytes were influenced by sport, but their individual variation over the sport season was not physiologically relevant (CV of 3.7 % and 21.3 %, respectively). When applying mathematical models for detection of rhEPO administration, only one elite athlete obtained an individual model score above the established thresholds. Physical fitness, sport and different training workload during the sport season had no substantial effect on serum EPO and sTfR concentrations, except in recreational athletes after a 21-km race. Variations observed in mathematical models to detect EPO administration were mainly due to fluctuation in hemoglobin concentrations, commonly observed in elite athletes.

Dependencia funcional y deterioro cognitivo de pacientes con cáncer avanzado atendidos en domicilio / No disponible

Objetivo: evaluar la dependencia funcional y deterioro cognitivo de los pacientes con cáncer avanzado atendidos en sus domicilios dentro de un programa de cuidados paliativos desarrollado por una Unidad de Hospitalización a Domicilio perteneciente a un hospital de tercer nivel («agudos»). Material y método: se analizan 1.423 pacientes que corresponden a la totalidad de enfermos de cáncer avanzado atendidos por la unidad entre enero de 2000 y diciembre de 2005. Resultados: destaca la fuerte dependencia física y marcado deterioro cognitivo de los pacientes al ingreso en programa con media de índice de Barthel de 34 y test de Pfeiffer mayor de 4 en el 50% de los casos. La estancia media fue de 12,5 días (DS 18). El 56% (797) de los pacientes falleció en su propio domicilio, el 10,8 (153) reingresó en nuestro hospital y el 6,8 (97) se derivó a una Unidad de Cuidados Paliativos de hospital sociosanitario. Los pacientes que fallecieron en el domicilio eran mayores (71 años) que los que reingresaron en el hospital (66) (p < 0,01) y presentaron al ser incluidos en programa mayor nivel de dependencia funcional (Barthel medio: 22,3 y 49,5 respectivamente, p < 0,001) y deterioro cognitivo (Pfeiffer medio 5,8 vs. 2,5, p < 0,001). Conclusiones: la complejidad relacionada con la dependencia funcional y el deterioro cognitivo de los pacientes y, como consecuencia, con la carga de cuidados que necesitan, no determina el lugar de la muerte. La edad de los enfermos es un factor modulador de la ubicación del paciente a lo largo de la evolución de su enfermedad (AU)

Objective: To assess functional dependence and cognitive deterioration in patients with advanced cancer cared for at home as part of a palliative care programme developed by a Hospitalisation at Home Unit at a level-three (acute) hospital. Material and method: 1,423 patients were analyzed, representing all patients with advanced cancer cared for at the Unit between January 2000 and December 2005. Results: It was noted that patients had major physical dependence and marked cognitive deterioration when they entered the program, since 50% of cases presented a mean of 34 on the Barthel index and over 4 in Pfeiffer's test. Mean stay was 12.5 days (SD 18). 56% of patients (797) died at home, 10.8% (153) were readmitted to our hospital, and 6.8% (97) were referred to a palliative care unit of a socio-sanitary hospital. Patients who died at home were older (71 years) than those who were readmitted to hospital (66) (p < 0.01), and on entry to the program they displayed a higher level of functional dependence (Barthel mean: 22.3 and 49.5 respectively, p < 0.001) and cognitive deterioration (Pfeiffer mean 5.8 vs.2.5, p < 0.001). Conclusions: The complexity of patients' functional dependence and cognitive deterioration, and the resulting care burden, does not determine the place of death. Patient age is a regulatory factor with regard to where patients are cared for as their disease progresses (AU)

Effect of physical fitness and endurance exercise on indirect biomarkers of recombinant growth hormone misuse: insulin-like growth factor I and procollagen type III peptide.

Serum insulin-like growth factor-I (IGF-I) and procollagen type III peptide (P-III-P) have been proposed as indirect biomarkers of rhGH misuse in sports. The purpose of the present study was to investigate concentrations of these biomarkers in athletes at different levels of physical fitness and endurance exercise. Serum total IGF-I and P-III-P were measured in 96 elite athletes of various sports along the training season; in 21 recreational athletes at baseline non-exercising conditions and in another 129 recreational athletes before and after long-distance races (10 and 21 km). No differences were evidenced for IGF-I concentrations, but statistically higher values of serum P-III-P were found in elite athletes compared to recreational ones. Among elite athletes, the specific sport did not affect serum IGF-I. However, P-III-P was statistically higher in the sport performed by the youngest athletes (rhythmic gymnastics), even after correction of the logarithm of the concentration by the reciprocal of age. Over the training season, the within-athlete variabilities of IGF-I and P-III-P in elite athletes were low (22.8 % and 21.7 %, respectively). Recreational athletes taking part in a 21 km competition race showed a significant increase in serum values of IGF-I and P-III-P immediately after the event. Exercise workload and age had a significant effect on serum concentration of P-III-P, while age alone affected IGF-I serum concentrations. Therefore, athlete's reference concentration ranges for doping detection should include subjects from as many different ages and sports as possible.

Nosocomial enterococcal endocarditis: a serious hazard for hospitalized patients with enterococcal bacteraemia.

OBJECTIVES: Enterococci are a major leading cause of infectious endocarditis and also a common cause of hospital-acquired bacteraemia, which is not believed to represent a serious hazard for the endocarditis. The incidence and risk factors for infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is determined. METHODS: Prospective analysis of 116 patients with enterococcal bacteraemia admitted to medical or surgical wards of a tertiary-care, university affiliated hospital during a period of 5 years. Echocardiography was performed when indicated by clinical criteria. RESULTS: Seventy-five (61.4%) episodes were hospital-acquired and 47 (38.5%) were community-acquired. Most patients had one or more underlying chronic diseases and major abdominal (58.6%) or genitourinary (38.6%) surgery. Seventeen patients (14.6%) developed enterococcal endocarditis. By univariate analysis the risk factors associated with endocarditis were community-acquired infection (P 0.012); monomicrobial bacteraemia (P 0.006); three or more positive blood cultures (P < 0.001); underlying valvulopathy (P < 0.001); presence of a prosthetic valve (P < 0.001) and age (P 0.012). Six patients (8%) developed nosocomial endocarditis. In this group of patients, three or more positive blood cultures (P < 0.01), bacteraemia as a result of Enterococcus faecalis (P 0.007); underlying valvulopathy (P < 0.001) and presence of a prosthetic valve (P < 0.001) were associated with endocarditis. By logistic regression, the presence of underlying valvulopathy and three or more positive blood cultures were associated with endocarditis (OR 21.0; CI 95% 1.65-26.9; P 0.019). CONCLUSIONS: The risk of developing infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is significant. Patients with underlying valvulopathy and three or more positive blood cultures with E. faecalis are prone to nosocomial enterococcal endocarditis.

Caracterización y estudio de solubilidad de mezclas binarias de flunarizina / polietilenglicol 4000 / Characterization and solubility study of binary mixtures of flunarizine/ polyethylene glycol 4000

En este trabajo estudiamos las interacciones de la flunarizina con polietilenglicol 4000 en dispersiones sólidas preparadas siguiendo el método de disolución propuesto por Sekiguchi y Obi. Como elementos de comparación se han utilizado mezclas físicas de ambos componentes, preparados en las mismas proporciones de fármaco/polímero: 10/ 90, 20/80, 30/70, 40/60, 50/50,60/40 y 80/20.Las propiedades fisicoquímicas de las dispersiones sólidas y mezclas físicas se investigan mediante espectroscopía infrarroja, difracción de rayos X, calorimetría diferencial de barrido y solubilidad en equilibrio. Los espectros de infrarrojo indican que no ha habido interacción química entre la flunarizina y el PEG. Los difractogramas muestran que a determinadas proporciones, el PEG se introduce en la estructura de la flunarizina y los estudios térmicos parecen indicar la formación de una mezcla eutéctica a la proporción 28,96 por ciento de flunarizina y 71,04 por ciento de PEG 4000. Todas las muestras presentan una solubilidad superior a la del fármaco puro y en ambos tipos de muestras el incremento es mayor al aumentar la proporción de polímero. El análisis de comparación múltiple aplicado independientemente a las dispersiones sólidas y mezclas físicas, indica que no existe diferencia estadísticamente significativa (p<0,05) entre las muestras de proporciones 30/70, 40/60. 50/50 y 60/40, pero sí hay diferencias entre éstas y las de proporciones 10/90, 20/80 y 80/20 (AU)

Síndrome de hipersensibilidad y fármacos antirretrovirales: descripción de dos casos / Drugs surveillance: hypersensitivity syndrome and antiretroviral drugs: report of two cases

No disponible

[Profile of primary care physicians in a health area: a cluster analysis]. / Perfil de los médicos de atención primaria en un área de salud: un análisis de clusters.

OBJECTIVES: To discover characteristics of primary care doctors. To find homogeneous groups of doctors. DESIGN: A basically descriptive crossover observational study. SETTING: Primary care doctors from a health area. PARTICIPANTS: The following variables were recorded on the 99 doctors who worked in Castellon Area 03 during 1992: age, gender, fixed or temporary post, rural or urban area, MIR training, primary care model, patient load, sole employment, drugs expenditure, number of pensioners and total number of patients registered. MEASUREMENTS AND MAIN RESULTS: We found a first group of older doctors, working mainly in the old model, for whom PC was not their sole employment; another younger group without MIR training and with an average patient load; the third group was women in temporary posts with a somewhat higher drugs expenditure; the fourth was doctors working in rural areas with a very low patient load; the fifth, final and youngest group was family doctors, with an average patient load, low expenditure and a high number of patients registered. We observed highly significant differences between groups. CONCLUSIONS: Doctors' age and gender divide them into different groupings; family doctors form one group. Multivariable, descriptive methods proved useful in finding, describing and classifying doctors and centres, etc., and could be of use in resource and action planning.

Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications.

The aim of the study was to characterize, from the relationship between total and free serum levels of valproic acid obtained over a broad dosage range (10-50 mg/kg), the parameters defining the in-vivo kinetic behaviour of the binding of valproic acid to plasma proteins, their pharmacokinetic and clinical repercussions, and their application to therapeutic drug monitoring (TDM). The study was performed in nine healthy adults (20-35 years) who were given doses of 1000 (group A), 2000 (group B) and 3000 mg (group C) of sodium valproate according to a compensated cross-over design, simultaneously determining the total and free serum levels of valproic acid over a 24-h period. The mean free fraction increases with dose, although this increase is only significant (P < 0.05) for the highest dose (3000 mg). The variation in the free fraction of valproic acid begins to become significant (P < 0.05) at a total drug concentration above 100 mg/l. The mean values of the dissociation constant (K) and binding sites (n) were 460 mumol/l and 1.79, respectively, showing a variability of 86.6 and 38.7%, respectively, and a residual variability of 13.0%. Significant differences (P < 0.05) were found for the total plasma clearance (Cl) but not for the intrinsic plasma clearance (Clu) values, despite their tendency to decrease with the dose. If TDM is to be used for valproic acid, it is the free serum levels that should be determined, especially if high doses are administered, because the total serum levels are not a true reflection of the free ones, as is the case of other anti-epileptic drugs.