Albumin-induced apoptosis of tubular cells is modulated by BASP1.

Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6-48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.

Increasing serum calcium levels and recent return from transplantation as clues to the tuberculous nature of refractory peritoneal dialysis peritonitis.

Peritoneal tuberculosis is an uncommon complication of peritoneal dialysis in Europe. It is more common in Asian immigrants. A delayed diagnosis is frequent and impairs patient outcomes. We present two cases of peritoneal tuberculosis with common features that may help suspect the disease early countries with a low incidence. Both patients were females (of Spanish origin) who had recently restarted peritoneal dialysis following kidney transplantation. Both developed bacterial peritonitis clinically that was refractory to conventional antibiotics, despite clearance of bacteria. Both stopped calcium-containing phosphate binders because of increasing serum calcium that in one case led to frank hypercalcemia that persisted despite low calcium dialysate. Peritoneal biopsy was the first positive test in both cases. This report emphasizes the recent return from transplantation and rising serum calcium levels as features that should alert the physician of a potential underlying tuberculous peritonitis.

Severe acute kidney injury in a patient with paroxysmal nocturnal haemoglobinuria.

A 32-year-old man previously diagnosed with paroxysmal nocturnal haemoglobinuria presented with a haemolytic episode and severe acute kidney injury that failed to respond to medical intensive therapies and needed renal replacement therapy.This is an exceptional complication of this disease.

2012 update on diabetic kidney disease: the expanding spectrum, novel pathogenic insights and recent clinical trials.

Diabetic kidney disease (DKD) is the most frequent cause of end-stage renal disease in western countries. This implies that current methods based of renin angiotensin aldosterone system (RAAS) targeting for preventing, slowing or promoting regression of DKD are insufficient. Podocyte injury and albuminuria are thought to be key events in DKD. Indeed several DKD stages are recognized based on the magnitude of albuminuria. However, the spectrum of DKD has recently expanded, as lack of significant albuminuria is present in 30% of diabetics with kidney function impairment. This may result from the widespread use of drugs targeting the RAAS. However, it may also indicate that additional pathogenic factors contribute to renal function deterioration despite control of albuminuria. In this regard, double blockade of the RAAS is more effective in reducing albuminuria that blockade of a single component. However, clinical trials assessing double blockade for renal function preservation have been disappointing and raised safety issues. Non-biased -omics approaches have uncovered alternative therapeutic targets, including the cytokine TRAIL, the MIF receptor CD74 and the proapoptotic intracellular protein BASP1. In addition, urinary proteomics has uncovered a peptidomic fingerprint for DKD progression that precedes the onset of microalbuminuria. Studies are underway to validate this fingerprint for early treatment of high risk patients. Recent clinical trials suggest a potential role of bardoxolone methyl to improve renal function in advanced DKD, while trials of avosentan, pirfenidone, sulodexide and pyridoxamine have been disappointing and further data are needed for paricalcitol and vitamin D, newer generation endothelin receptor antagonists and pentoxifylline.

Calidad asistencial y satisfacción del usuario. Análisis de la satisfacción e insatisfacción de los usuarios del Hospital Universitario Central de Asturias a través de las reclamaciones / Healthcare quality and user satisfaction: analysis of the users ´satisfaction and dissatisfaction of the Hospital Universitario Central de Asturias though an analysis of complaints

Las reclamaciones recogen aspectos que determinan la satisfacción e insatisfacción de los usuarios y aportan información muy valiosa para la mejora de los procesos de atención. El objetivo de este estudio es el de analizar los elementos que generan insatisfacción en los usuarios de un Centro Hospitalario a través de las reclamaciones presentadas. Se realizó un estudio descriptivo de las reclamaciones presentadas en el Hospital Universitario Central de Asturias durante el periodo 2002-2006. Efectuando un análisis del contenido de las quejas del año 2006 se constata que los Problemas de Relación y Comunicación son el principal motivo de reclamación de los usuarios con un porcentaje del 39% sobre el total. Se concluye que la relación y la comunicación profesional-usuario son aspectos que los usuarios valoran enormemente y determina en gran medida el grado de satisfacción e insatisfacción con los Servicios Sanitarios. Además influyen sobre otras variables como son la confianza en el profesional y la percepción de eficacia y calidad del Servicio. Por tanto, la Relación y la Comunicación son elementos fundamentales en el proceso de mejora de la calidad asistencial y deberían de tenerse en cuenta en la planificación (AU)

The complaints record collects aspects which determine the users’ satisfaction and dissatisfaction and provides very valuable information for improving healthcare procedures. The relationship and communication between professionals and users are aspects which the users value highly and they determine to a large extent the degree of satisfaction and dissatisfaction with the Health Services. These also have an influence on other variables such as the users´ confidence in the professionals and their perception of the efficiency and quality of the Service. Relationships and communication are therefore key elements in the process of improving healthcare and should be taken into account in planning (AU)

Contribución de la detección radioguiada y biopsia selectiva del Ganglio centinela al estadiaje de 100 pacientes con melanoma cutáneo / Contribution of the radioguided detection and selective biopsy of the sentinel lymph node with staging in 100 patients with cutaneous melanoma

Objetivo: La biopsia selectiva del Ganglio Centinela (GC) se ofrece como una alternativa a la linfadenectomía regional convencional en el estadiaje de pacientes con melanoma cutáneo maligno. El objetivo de este trabajo es analizar nuestra experiencia en la localización del GC mediante linfogammagrafía y sonda detectora y su utilidad en el estadiaje del melanoma cutáneo maligno (MCM).Material y Métodos: Se estudiaron 100 pacientes, 56 mujeres y 44 hombres, con edad media de 51,5 ñ 31,5 años, diagnosticados de MCM. En todos los casos se realizó linfografía radioisotópica pre-operatoria para detectar el área ganglionar de drenaje tras administración intradérmica peritumoral de 600 microCi de 99mTc- sulfuro coloidal, adquiriendose imágenes planares cada 10 minutos hasta la localización de actividad en áreas ganglionares de drenaje. Posteriormente se efectuó localización intraoperatoria mediante sonda detectora y biopsia selectiva del GC, enviándose al Servicio de Anatomía Patológica para evaluar infiltración metastásica. Resultados: El estudio linfogammagráfico resultó positivo en 99 de los 100 casos, siendo identificados intraoperatoriamente 98 casos. El análisis anatomopatológico fue negativo en el 78,9 por ciento y positivo en el 21,1 por ciento de los ganglios extraídos. Conclusiones: La linfografía radioisotópica y la detección intraoperatoria son dos técnicas extraordinariamente útiles en la localización del GC y estadiaje del MCM. Son muchos los pacientes que se benefician de la biopsia selectiva radioguiada del GC en ésta patología tumoral, tanto en disminución de la morbilidad de la intervención como en un mejor estadiaje de la enfermedad. (AU)

[Contribution of radioguided detection and selective biopsy of the sentinel lymph node to staging in 100 patients with cutaneous melanoma]. / Contribución de la detección radioguiada y biopsia selectiva del Ganglio centinela al estadiaje de 100 pacientes con melanoma cutáneo.

OBJECTIVE: A selective sentinel node (SN) biopsy appears to be an alternative to conventional lymph node dissection for staging patients with cutaneous melanoma. This study has aimed to analyze our experience in the localization of the sentinel node with a probe detector and lymphoscintigraphy and its utility in the staging of this disease. MATERIAL AND METHODS: 100 patients, 56 female and 44 male, 51.5 31.5 mean age, diagnosed of cutaneous melanoma were studied. The lymphoscintigraphy was performed in all cases to detect the area of lymphatic drainage after peritumoral intradermal administration of 600 uCi of 99mTc-colloidal sulfur, and planar images were acquired every 10 minutes until activity was detected in these areas. Afterwards, the intraoperative localization of the sentinel node with a probe detector was performed and the selective biopsy of the node was sent to the Pathology Department for its histologic study. RESULTS: The lymphoscintigraphy study was positive in 99 of the 100 cases and it was identified intraoperatively in 98 cases. The histologic analysis was negative in 78.9% and positive in 21.1% of the nodes. CONCLUSIONS: Radioisotopic lymphography and intraoperative probe detection are two very useful techniques for locating the sentinel node and staging patients with cutaneous melanoma. Many patients are benefiting from the selective biopsy of the sentinel node because of the decreased post-surgical morbidity and better staging of the cutaneous melanoma.

[Clinical and epidemiological spectrum of Mycoplasma pneumoniae infections at a pediatric hospital]. / Espectro clínico-epidemiológico de las infecciones por Mycoplasma pneumoniae en un hospital infantil.

OBJECTIVE: The objective of this study was to determine the epidemiology of Mycoplasma pneumoniae infections at our hospital and to evaluate the prescription of macrolides to empirically treat respiratory infections in children. PATIENTS AND METHODS: A one year prospective study was performed. To find out the prevalence of M. pneumoniae infections, we obtained blood samples of 519 children attending our hospital out-patient department to determine M. pneumoniae IgG levels. In order to establish the incidence, IgM antibodies against M. pneumoniae were measured in 255 children admitted to the hospital showing clinical pictures compatible with this infection. RESULTS: In the first years of life, prevalence of M. pneumoniae infection was low. According to our study, only 3.3% of 1 year-old patients had M. pneumoniae antibodies. Antibody levels increased in children of 5 years or older. The highest rates, between 58.5% and 63.3%, were detected in patients between 8 and 12 years of age. The incidence rate (6.7%) was low among the children admitted. The most frequent clinical entity was pneumonia (82%). The highest rate of infection was found in children of 8 to 10 years. Symtomatology was mainly sub-acute. Crioagglutinins provided the most significant predictive value for etiological diagnosis. CONCLUSIONS: M. pneumoniae infections gain significance in patients over 5 years of age. In our environment, incidence of acute symptomatic infection is low. We consider that both age and presentation of acute respiratory processes should be taken into account when establishing empirical macrolide treatment in children.

[Evaluation of cardiac sympathetic innervation with 123I-metaiodobenzylguanidine in patients with diabetes mellitus]. / Valoración de la inervación simpática cardíaca con 123I-metayodobencilguanidina en pacientes con diabetes mellitus.

OBJECTIVES: To evaluate the usefulness of iodine-123 metaiodobencylguanidine (123I-MIBG) in the study of the cardiac autonomic neuropathy in insulin-dependent diabetic patients, by means of: a) analysis of heart to mediastinic ratio and tomographic images with 123I-MIBG; b) comparison with conventional non-invasive cardiac reflex test, and c) analysis of left ventricle ejection fraction. POPULATION AND METHODS: Ten patients submitted for cardiac evaluation with 123I-MIBG were compared with a control group of 11 patients. In both groups we excluded the presence of coronary pathology by means of an exercise test. We carried out planar and SPECT studies, using 123I-MIBG, and the calculation of the ejection fraction by equilibrium ventriculography. RESULTS: The uptake of 123I-MIBG in diabetic patients was significantly smaller than the control group in the calculated index (heart to mediastinic ratio: 1.64 +/- 0.20 vs 2.00 +/- 0.26; p < 0.001; SPECT index: 44.87 +/- 8.37 vs 55.54 +/- 3.96; p < 0.001). In polar images we noted a more reduced uptake in the diabetic group in the inferior wall (p = 0.020). Patients with cardiac sympa-thetic dysinnervation demonstrated less uptake in both indexes (p < 0.05 and 0.005, respectively), essentially in the inferior wall and in basal and medium territories (p < 0.05). No differences in respect to the ejection fraction parameter were found. CONCLUSIONS: Despite the small sample population, insuli-dependent diabetic patients in show a significant reduction of the uptake of 23I-MIBG, more accentuated in the base. Scintigraphy using 123I-MIBG can be an approach to investigate the pattern and the natural history of the sympathetic innervation in these patients.