RESUMEN
INTRODUCTION: Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. MATERIALS AND METHODS: Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. RESULTS: Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p < 0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p < 0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). CONCLUSIONS: Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.
Asunto(s)
Infecciones por Virus ADN , Trasplante de Riñón , Torque teno virus , Adulto , Humanos , Trasplante de Riñón/efectos adversos , Torque teno virus/genética , Rechazo de Injerto , Cinética , Carga Viral , Estudios Prospectivos , ADN Viral/genéticaRESUMEN
Since January 2015 we have carried out a multiple-intervention strategic plan to reduce hospital stay in renal transplant recipients. The main objective of this study is to compare results of renal transplantation before and after putting into effect this plan in terms of graft and patient survival, readmissions and incidence of acute rejection during the first year post transplantation. In this retrospective analysis we included all patients 18 years of age or older who were transplanted at our institution. The strategic plan resulted in a significant reduction of hospital stay of renal recipients from 13.5 days in the pre-plan group (n=97) to 4.6 days in the post-plan group (n=62; p≤0.0001). The incidence of acute rejection during the first year was similar (pre-plan group=14.4% vs. post-plan group=16% [p=0.77]) as it was graft survival (88% vs. 90% [p=0.71]) and patient survival (95% vs. 98% [p=0.37]), respectively. The multiple-intervention strategic plan has significantly reduced the hospital stay of patients after renal transplantation without affecting graft or patient survival, which are comparable to those internationally published, and without jeopardizing patient's safety.
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Rechazo de Injerto/epidemiología , Implementación de Plan de Salud , Trasplante de Riñón/mortalidad , Trasplante de Riñón/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Factores de Edad , Análisis de Varianza , Femenino , Supervivencia de Injerto , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Introducción: En la fase aguda del ictus el 30% de los pacientes presentan disfagia, y de ellos, el 50% experimentarán broncoaspiración. Nuestro objetivo fue evaluar los resultados de mortalidad y broncoaspiración del test del agua comparado con el test 2 volúmenes/3 texturas controlado con pulsioximetría (2v/3t-P) en una unidad de ictus. Pacientes y métodos: Durante 5 años se analizaron de forma prospectiva y consecutiva todos los pacientes con infarto cerebral en la Unidad de Ictus. Del año 2008 al 2010 se utilizó el test del agua (grupo 0 o G0), y del 2011 al 2012, el test 2v/3t-P (grupo 1 o G1). Se recogieron las siguientes variables: demográficas, factores de riesgo vascular, gravedad neurológica con la escala NIHSS, subtipo etiológico según criterios TOAST, subtipo clínico según la clasificación Oxfordshire, prevalencia de disfagia, broncoaspiración y exitus. Resultados: Se analizaron 418 pacientes con infarto cerebral agudo (G0 = 275, G1 = 143). Se detectaron diferencias significativas entre ambos grupos en el porcentaje de pacientes con TACI (17% en G0 vs. 29% en G1, p = 0,005) y en la mediana de NIHSS (4 puntos en G0 vs. 7 puntos en G1, p = 0,003). Con el test 2v/3t-P se detectó un aumento no significativo en el porcentaje de disfagia (22% en G0 vs. 25% en G1, p = 0,4), una menor tasa de mortalidad (1,7% en G0 vs. 0,7% en G1, p = 0,3) y una reducción significativa de broncoaspiración (6,2% en G0 vs. 2,1% en G1, p = 0,05). Conclusiones: El nuevo test 2v/3t-P, comparado con el test del agua, mejoró significativamente los resultados de broncoaspiración en los pacientes con infarto cerebral agudo
Introduction: During acute stroke, 30% of all patients present dysphagia and 50% of that subgroup will experience bronchoaspiration. Our aim was to compare mortality and bronchoaspiration rates associated with the water test compared to those associated with a 2 volume/3 texture test controlled with pulse oximetry (2v/3t-P test) in our stroke unit. Patients and methods. Over a 5-year period, we performed a prospective analysis of all consecutive acute ischaemic stroke patients hospitalised in the Stroke Unit. Dysphagia was evaluated using the water test between 2008 and 2010 (group 0 or G0), and the 2v/3t-P test (group 1 or G1) between 2011 and 2012. We analysed demographic data, vascular risk factors, neurological deficit on the NIHSS, aetiological subtype according to TOAST criteria, clinical subtype according to the Oxfordshire classification, prevalence of dysphagia, percentage of patients with bronchoaspiration, and mortality. Results: We examined 418 patients with acute stroke (G0 = 275, G1 = 143). There were significant differences between the 2 groups regarding the percentage of patients with TACI (17% in G0 vs. 29% in G1, P = .005) and median NIHSS score (4 points in G0 vs. 7 points in G1, P = .003). Since adopting the new swallowing test, we detected a non-significant increase in the percentage of dysphagia (22% in G0 vs. 25% in G1, P = .4), lower mortality (1.7% in G0 vs. 0.7% in G1, P = .3) and a significant decrease in the bronchoaspiration rate (6.2% in G0 vs. 2.1% in G1, P = .05). Conclusions: Compared to the water test used for dysphagia screening, the new 2v/3t-P test lowered bronchoaspiration rates in acute stroke patients
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Humanos , Masculino , Femenino , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiología , Trastornos de Deglución/complicaciones , Trastornos de Deglución/diagnóstico , Biopsia con Aguja/estadística & datos numéricos , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Estudios Prospectivos , Deglución , Indicadores de Morbimortalidad , Análisis MultivarianteRESUMEN
INTRODUCTION: During acute stroke, 30% of all patients present dysphagia and 50% of that subgroup will experience bronchoaspiration. Our aim was to compare mortality and bronchoaspiration rates associated with the water test compared to those associated with a 2 volume/3 texture test controlled with pulse oximetry (2v/3t-P test) in our stroke unit. PATIENTS AND METHODS: Over a 5-year period, we performed a prospective analysis of all consecutive acute ischaemic stroke patients hospitalised in the Stroke Unit. Dysphagia was evaluated using the water test between 2008 and 2010 (group 0 or G0), and the 2v/3t-P test (group 1 or G1) between 2011 and 2012. We analysed demographic data, vascular risk factors, neurological deficit on the NIHSS, aetiological subtype according to TOAST criteria, clinical subtype according to the Oxfordshire classification, prevalence of dysphagia, percentage of patients with bronchoaspiration, and mortality. RESULTS: We examined 418 patients with acute stroke (G0=275, G1=143). There were significant differences between the 2 groups regarding the percentage of patients with TACI (17% in G0 vs. 29% in G1, P=.005) and median NIHSS score (4 points in G0 vs. 7 points in G1, P=.003). Since adopting the new swallowing test, we detected a non-significant increase in the percentage of dysphagia (22% in G0 vs. 25% in G1, P=.4), lower mortality (1.7% in G0 vs. 0.7% in G1, P=.3) and a significant decrease in the bronchoaspiration rate (6.2% in G0 vs. 2.1% in G1, P=.05). CONCLUSIONS: Compared to the water test used for dysphagia screening, the new 2v/3t-P test lowered bronchoaspiration rates in acute stroke patients.
Asunto(s)
Trastornos de Deglución/diagnóstico , Tamizaje Masivo , Accidente Cerebrovascular/complicaciones , Anciano , Trastornos de Deglución/etiología , Femenino , Hospitalización , Humanos , Masculino , Prevalencia , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: The use of expanded criteria donor (ECD) kidneys has increased the overall availability of renal transplants. This study assessed the use of sirolimus in patients receiving Argentina-ECD kidneys. METHODS: This observational, open-label, 1-arm, prospective, longitudinal pilot study was conducted at 8 transplant centers in Argentina. Adults receiving kidney transplants (without pancreas) from ECDs were eligible if they were converted to sirolimus 1 to 36 months' posttransplantation, with sirolimus becoming base therapy within 1 month after conversion. Patients were followed up for 1 year. Outcomes included reasons for conversion, acute rejection, patient and graft survival, graft status, and safety. RESULTS: The intention-to-treat population included 52 patients (mean age, 48.7 years). Calcineurin inhibitor nephropathy (40%) and chronic allograft nephropathy (25%) were the most frequent reasons for conversion. Two acute rejections occurred during follow-up, but no patients experienced graft loss. One patient died during follow-up, and 3 patients died within 1 month of the last sirolimus dose. Levels of serum creatinine and creatinine clearance remained stable from baseline to week 52/53. Mean proteinuria measured in a subset of patients was 0.2 ± 0.2 g/24 hours before conversion and increased to 0.6 ± 1.2 g/24 hours at week 24/25 and 0.5 ± 0.6 g/24 hours at week 52/53. Adverse events were consistent with those in previous conversion trials; the most common were infections and infestations (54%). CONCLUSIONS: This pilot study illustrates the potential benefits of sirolimus in recipients of ECD kidneys in Argentina. Larger, randomized controlled trials are needed to confirm these findings and to clarify the long-term benefits of sirolimus in this patient population.
Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Sirolimus/uso terapéutico , Donantes de Tejidos/provisión & distribución , Adulto , Anciano , Aloinjertos , Argentina , Femenino , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/mortalidad , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Sistema de RegistrosRESUMEN
En Argentina no se han realizado estudios destinados a establecer la prevalencia de disglucemias (glucemia alterada en ayunas [GAA], tolerancia alterada a la glucosa [TAG] y diabetes mellitus [DM]) en pacientes con enfermedad renal. Se decidió realizar un estudio observacional, evaluando la frecuencia con prueba de tolerancia oral a glucosa (PTOG) en pacientes con enfermedad renal crónica (ERC), sin registro de disglucemia en sus historias clínicas. Se realizó PTOG a 254 pacientes (60,62% masculinos), con ERC estadios 3, 4 y 5, en tratamiento conservador, hemodiálisis o trasplante. Los resultados mostraron pacientes con valores de DM: 10 pacientes según ayunas exclusivamente (3,94%; IC 95%: 1,35-6,53%); exclusivamente segunda hora, 11 pacientes (4,33%; IC 95%: 1,63-7,03%); por ambos criterios, 15 pacientes (5,91%; IC 95%: 2,81-9,00%); por al menos un criterio, 36 pacientes (14,17%; IC 95%: 9,69-18,66%). En análisis multivariado, la DM se asoció con valor de cintura (OR=1,033 por cm; IC 95%: 1,005-1,062; p=0,019) y con tratamiento sustitutivo vs. conservador (OR=0,41; IC 95%: 0,19-0,92; p=0,028). La GAA (criterio ADA) fue del 19,75% en tratamiento conservador vs. 9,24% en tratamiento sustitutivo, con diferencia estadísticamente significativa. No fue significativa la diferencia de TAG que evidenció 24,6 y 20,3% en tratamiento conservador y sustitutivo, respectivamente. Se propone la realización de PTOG en todo paciente con ERC, ya que permite la detección de todo el rango de disglucemias desconocidas, evitando el subdiagnóstico y favoreciendo la realización de tratamientos para evitar su progresión, en caso de estar ante la presencia de un grupo de riesgo para DM (GAA o TAG), así como la elección de la medicación más adecuada para el trasplante o el inicio del tratamiento de nuevos casos de DM no diagnosticada, para disminuir la morbimortalidad (AU)
In Argentina, there have been no studies aimed at establishing the prevalence of dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] and diabetes mellitus [DM]) in patients with chronic kidney disease (CKD). Our group decided to conduct an observational study to evaluate the frequency with oral glucose tolerance test (OGTT) in CKD patients with no previous data for dysglycaemia in their medical records. OGTT was performed in 254 patients (60.62% male) with stage 3, 4 and 5 CKD under conservative treatment, haemodialysis or transplantation. Results for DM were found in 10 patients according to fasting glucose alone (3.94%; 95% CI: 1.35-6.53%), 11 patients with exclusively the second hour criterion (4.33%; 95% CI: 1.63-7.03%), 15 with both criteria (5.91%; 95% CI: 2.81-9.00%) and 36 patients with at least one criteria (14.17%; 95% CI: 9.69-18.66%). In a multivariate analysis, DM was associated with waist circumference (OR=1.033 per cm; 95% CI, 1.005 to 1.062; P=.019) and with conservative treatment vs. replacement therapy (OR=0.41; 95% CI: 0.19-0.92;P=.028). IGT was evident in 24.6% and 20.3 on conservative vs. replacement therapy, with no statistically significant difference. IFG (ADA criteria) was 19.75 vs. 9.24% in conservative vs. replacement therapy, with a statistically significant difference. OGTT is suggested for all CKD patients since it is able to detect the full range of unknown dysglycaemias, which avoids underdiagnoses and favours performing treatments to prevent progression in DM risk groups (IFG and/or IGT). It also aids in the selection of the most appropriate medication for transplantation or treatment initiation in new cases of undiagnosed DM to decrease morbidity and mortality (AU)
Asunto(s)
Humanos , Insuficiencia Renal Crónica/complicaciones , Diabetes Mellitus/epidemiología , Glucemia/análisis , Prueba de Tolerancia a la Glucosa/estadística & datos numéricos , Ayuno/fisiología , Índice Glucémico , Diálisis Renal , Trasplante de RiñónRESUMEN
BACKGROUND: The worldwide seroprevalence of human BK polyomavirus (BKV) in adults is 80%. About 10%-60% of renal transplant recipients experience BKV infection, nephropathy of the graft may occur in 5% of the cases, and up to 45% lose the graft. The aim of this work was to describe the prevalence of BK viruria during the 1st year after transplantation. METHODS: An epidemiologic multicenter cross-sectional study was carried out in consecutive patients at each site with kidney transplantation from August 2011 to July 2012. Clinically significant viruria was defined as >10(7) copies/mL. Viral DNA was extracted with the use of silica columns. Quantification was performed with the use of real-time polymerase chain reaction with primers that amplify a fragment of the large T-antigen gene and with a specific Taqman-MGB probe for BKV. For each assay, a standard curve with a quantified plasmid was included. RESULTS: Of 402 renal transplant recipients at 18 renal transplant sites, we analyzed 382; median age was 46.33 years, and 46.40% were female. The median of the temporal distribution for urine samples was 153 days. BK virus was detected in 50/382 samples (13%), 18 with values >10(7) copies/mL (4.7%). The median of the distribution of positive values was 123 days and the highest frequency of positive values was in months 3-7. The conditions of recipient older than 34 years and donor older than 41 years were the only ones that showed statistically significant association with BK viruria. No association with any specific immunosuppressive drug was observed. CONCLUSIONS: This is the first multicenter study conducted in Argentina to determine the prevalence of BK viruria in renal transplant recipients. Because of the growing number of the population susceptible to this infection, it is important to register and describe data about its epidemiology and associated risk factors.
Asunto(s)
Virus BK/aislamiento & purificación , Trasplante de Riñón , Infecciones Oportunistas/epidemiología , Infecciones por Polyomavirus/epidemiología , Complicaciones Posoperatorias/epidemiología , Infecciones Tumorales por Virus/epidemiología , Adulto , Argentina , Virus BK/genética , Estudios Transversales , ADN Viral/análisis , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/etiología , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/etiología , Complicaciones Posoperatorias/diagnóstico , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/etiologíaRESUMEN
The Minimally Invasive Procedures (MIP) in orthopedics have grown rapidly worldwide, as clinical results indicate that patients who undergo MIP typically experience minimized blood loss, smaller incision and shorter hospital stays. For most MIP, a preoperative 3D model of the patient anatomy is usually generated in order to plan the surgery. The challenge in MIP consists in finding the correspondence between the preoperative model and the actual position of the patient in the operating room, also known as image-to-patient registration. This paper proposes a real-time solution based on ultrasound (US) images: the patient anatomy is scanned by an US probe. Then, the segmentation and the extraction of bone contours from US images result in a 3D point cloud. The Poisson surface reconstruction method provides a 3D surface from 2D US data which will be registered with the preoperative model (CT volume) using the principal axes of inertia and the Iterative Closest Point robust (ICPr) algorithm. We present quantitative and qualitative results on both phantom and clinical data and show a mean registration accuracy of 0.66 mm for clinical radius scan. The promising registration results show the possible use of the proposed registration algorithm in clinical procedures.
Asunto(s)
Automatización , Huesos/cirugía , Procesamiento de Imagen Asistido por Computador/métodos , Cuidados Intraoperatorios , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Cuidados Preoperatorios , Algoritmos , Huesos/diagnóstico por imagen , Humanos , Fantasmas de Imagen , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/cirugía , Reproducibilidad de los Resultados , UltrasonografíaRESUMEN
Introducción: Desde hace varios años, se ha producido un aumento en las visitas por patología psiquiátrica en los servicios de urgencias pediátricas. Por ello, es importante la coordinación entre los equipos de urgencias pediátricas y los de salud mental para mejorar la atención de los pacientes pediátricos con una enfermedad mental. Objetivos: Analizar las características de los pacientes pediátricos del servicio de urgencias psiquiátricas de nuestro hospital. Metodología: Estudio transversal descriptivo de las urgencias psiquiátricas atendidas en el Servicio de Urgencias de Pediatría que precisaron atención en el Servicio de Psiquiatría de la Corporació Sanitària «Parc Taulí» de Sabadell (periodo 2006-2007). Analizamos las variables sociodemográficas y los diagnósticos psiquiátricos, así como la necesidad de tratamiento y el destino final del paciente. Resultados: Se realizaron 104 visitas psiquiátricas de un total de 93.908 urgencias (0,1%), con una media de edad de los pacientes de 12,37 años (rango: 6-15). Los motivos de consulta principales fueron: empeoramiento de la enfermedad de base (51%), alteración de la conducta de diversos tipos (31,7%) e intento de suicidio (17,3%). Muchos de los casos presentaban factores asociados o distocia social: un 68,2% presentaba antecedentes de enfermedad familiar psiquiátrica, un 39,4% abuso de alcohol y/o drogas, y un 25,9% una separación traumática de los padres. Sólo un 26% de los casos precisaron una intervención farmacológica fuera de su tratamiento habitual. Los diagnósticos principales al alta fueron, en el 50% de los casos, trastornos de conducta no especificados y conversivos. Se dio de alta a su domicilio al 64% de los pacientes, y un 36% precisó ingreso hospitalario. Conclusiones: Las urgencias psiquiátricas pediátricas son complejas y graves. Últimamente se ha producido un aumento de ellas, lo que puede obedecer a múltiples causas, algunas de las cuales representan tendencias epidemiológicas que pueden estudiarse y preverse (AU)
Introduction: For several years, there is an increase in visits due to psychiatric disorders in the pediatric emergency departments. Therefore the coordination between pediatric emergency department and mental health department is important to improve the care of pediatric patients with mental illness. Objectives: To analyze the characteristics of pediatric patients in the Pediatric Emergency Department in our hospital. Methodology: Transversal and descriptive study of the psychiatric emergencies treated in the Pediatric Emergency Department which required attention by psychiatry of the Corporació Sanitària Parc Taulí (Sabadell) (period 2006-2007). We analyzed social demographic variables, psychiatric diagnoses, as well as the need of treatment and final destination of the patient. Results: There were 104 psychiatric visits of 93,908 emergencies (0.1%), with a mean age of 12.37 years (range: 6-15).The main reasons for consultation were: worsening of their underlying disease (51%), different kinds of conduct alteration(31.7%) and suicide attempt (17.3%). Many of the cases showed associated factors or social dystocia: 68.2% had family history of psychiatric illness, a 39.4% alcohol or drugs abuse and 25.9% had a traumatic parent divorce. Only 26% of the cases needed drug treatment other than their usual treatment. The main diagnosis at discharge was, in 50% of the cases, unspecified conduct disorder or conversion disorders. A 64% of the patients were discharged, and 36% required admission. Conclusions: The pediatric psychiatric emergencies are complex and serious. There is an increase of these, which may be due to multiple causes. Some of the causes represent epidemiological trends and can be studied and foreseen (AU)
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Trastornos del Neurodesarrollo/epidemiología , Intento de Suicidio/estadística & datos numéricos , Trastornos Mentales/epidemiología , Servicios Médicos de Urgencia/estadística & datos numéricos , Servicios de Salud del Niño/estadística & datos numéricosRESUMEN
Management of posttransplantation malignancies should include control of the neoplasia and preservation of renal function. Conversion to everolimus (EVL) would potentially have both effects. Twenty-one patients were converted to EVL due to posttransplantation neoplasms. We have presented herein descriptive data and postconversion (PC) outcomes among subjects of mean age 53.6 +/- 10.1 years (range, 36-69), 57.1% were males, undergoing conversion at 108.2 +/- 74.7 (range, 5-316) months after transplantation. All patients received standard immunosuppressive therapy and 9.5% had been induced with thymoglobulin. Malignant neoplasms were as follows: skin (n = 7), gynecological (n = 3), gastrointestinal (n = 3), PTLD (n = 2), renal (n = 2), CNS (n = 1), seminoma (n = 1), Kaposi's sarcoma (n = 1), and prostate cancer (n = 1). PC to EVL, calcineurin inhibitors (CNIs) were discontinued in 18 of 19 patients, mycophenolate in 9/12, and azathioprine in 5/7; all patients continued to receive steroids. In 16 patients (79%) tumors were removed. Chemotherapy was performed in 2 patients with PTLD and radiotherapy was performed in 1 patient with prostate cancer. Mean follow-up was 505 days (range, 59-1151); baseline glomerular filtration rate (GFR) was 53.5 +/- 21.6 mL/min versus 48.5 +/- 25.7 mL/min (P = not significant [NS]) at the last control. One patient experienced graft loss at day 744 after conversion due to chronic rejection. Adverse events were observed in 57% of patients and 28% displayed infections; no patient discontinued EVL. There were 2 deaths: 1 due to an infection and the other due to postsurgical complication. No deaths due to cancer progression were observed. The results observed in this series suggested that conversion to EVL for a posttransplantation neoplasm is a valid therapeutic alternative to preserve graft function and control disease progression.
Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Neoplasias/inmunología , Complicaciones Posoperatorias/inmunología , Sirolimus/análogos & derivados , Adulto , Anciano , Suero Antilinfocítico/uso terapéutico , Colesterol/sangre , Everolimus , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Neoplasias/cirugía , Recuento de Plaquetas , Neoplasias de la Próstata/radioterapia , Proteinuria , Sirolimus/uso terapéutico , Factores de Tiempo , Triglicéridos/sangreRESUMEN
The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney-pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr(baseline) 51.4 vs CCr(6m) 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0-453) versus 0 mg/24 hours (range, 0-309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 +/- 37 vs. 186.6 +/- 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.
Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Preservación de Órganos/métodos , Trasplante de Páncreas/inmunología , Sirolimus/uso terapéutico , Adulto , Biopsia , Creatinina/sangre , Creatinina/orina , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Trasplante de Riñón/patología , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/patología , Proteinuria , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Chronic hepatitis B and C viruses (HBV and HCV) are common problems in renal transplant patients. There is no uniform agreement regarding their influence on graft outcomes and patient survival. We evaluated the influence of anti-HCV and hepatitis B surface antigen-positive status; gender; age>49 years at the time of transplantation; alanine aminotransferase elevation; acute rejection; type of graft; number of transplants; and maintenance/induction immunosuppressive treatment on both graft and patient survivals among a population transplanted in our center between 1991 and 2004. Univariate analysis showed that anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. Over the age of 49 years at the time of transplantation, anti-HCV-positive status, cadaveric donor, kidney-pancreas transplantation, and three-drug immunosuppressive therapy were associated with diminished patient survival. Upon multivariate analysis, reduced patient survival was associated with the same variables as in the univariate analysis: anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. In our experience, anti-HCV-positive compared with anti-HCV-negative status was associated with a reduced graft (56% vs. 75%; P=.0002) and patient survival (68% vs. 83%; P=.0028).
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/complicaciones , Trasplante de Riñón/fisiología , Alanina Transaminasa/sangre , Femenino , Supervivencia de Injerto , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Sobrevivientes , Resultado del TratamientoAsunto(s)
Suplementos Dietéticos , Infecciones por VIH/complicaciones , Síndrome de Emaciación por VIH/prevención & control , Músculo Esquelético/crecimiento & desarrollo , Arginina/administración & dosificación , Butiratos/administración & dosificación , Dieta , Glutamina/administración & dosificación , Humanos , Estados Unidos , Levantamiento de PesoRESUMEN
The presence of ATP within cells is well established. However, ATP also operates as an intercellular signal via specific purinoceptors. Furthermore, nonsecretory cells can release ATP under certain experimental conditions. To measure ATP release and membrane currents from a single cell simultaneously, we used Xenopus oocytes. We simultaneously recorded membrane currents and luminescence. Here, we show that ATP release can be triggered in Xenopus oocytes by hyperpolarizing pulses. ATP release (3.2 +/- 0.3 pmol/oocyte) generated a slow inward current (2.3 +/- 0.1 microA). During hyperpolarizing pulses, the permeability for ATP(4-) was more than 4000 times higher than that for Cl(-). The sensitivity to GdCl(3) (0. 2 mm) of hyperpolarization-induced ionic current, ATP release and E-ATPase activity suggests their dependence on stretch-activated ion channels. The pharmacological profile of the current inhibition coincides with the inhibition of ecto-ATPase activity. This enzyme is highly conserved among species, and in humans, it has been cloned and characterized as CD39. The translation, in Xenopus oocytes, of human CD39 mRNA encoding enhances the ATP-supported current, indicating that CD39 is directly or indirectly responsible for the electrodiffusion of ATP.
Asunto(s)
Adenosina Trifosfato/metabolismo , Membrana Celular/metabolismo , Canales Iónicos/metabolismo , Oocitos/metabolismo , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/farmacología , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Apirasa , Permeabilidad de la Membrana Celular , Cianuros/farmacología , Humanos , Oocitos/enzimología , Técnicas de Placa-Clamp , Biosíntesis de Proteínas , XenopusRESUMEN
The PPX/PP4 Ser/Thr protein phosphatases belong to the type 2A phosphatase subfamily and are present in most eukaryotic organisms. We have previously isolated two closely related DNAs encoding PPX isoforms (PPX-1 and PPX-2) of Arabidopsis thaliana. Here we report the molecular cloning of the genes encoding these proteins. The genes PPX-1 and PPX-2 are composed of eight exons and seven introns located at equivalent positions related to the coding sequences. Whereas the intron-exon organization of the PPX genes is completely different from that of the PP2A-3/PP2A-4 A. thaliana family, specific intron-exon boundaries are conserved among PPX genes from distantly related organisms. Based on GUS expression, both PPX genes show the same spatial and temporal pattern of expression: they are expressed in all the organs and tissues analyzed, and from the earliest stage of development. When PPX proteins were localized to the root in semi-thin methacrylate sections by immunofluorescence, staining was predominantly confined to small organelles, shown to be plastids by co-localization of PPX and ferredoxin. Interestingly, only some ferredoxin-positive plastids were also PPX-positive, and PPX staining was consistently brighter in the epidermis. The localization was confirmed with immunogold and electron microscopy. Our results suggest that, despite its strong sequence conservation, PPX in plants functions differently than in animals.
Asunto(s)
Arabidopsis/genética , Fosfoproteínas Fosfatasas/genética , Arabidopsis/enzimología , Arabidopsis/ultraestructura , Clonación Molecular , ADN de Plantas/química , ADN de Plantas/genética , Exones , Regulación Enzimológica de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genes de Plantas/genética , Glucuronidasa/genética , Glucuronidasa/metabolismo , Intrones , Isoenzimas/genética , Microscopía Inmunoelectrónica , Datos de Secuencia Molecular , Plantas Modificadas Genéticamente/enzimología , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plastidios/enzimología , Plastidios/ultraestructura , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Análisis de Secuencia de ADN , Distribución TisularRESUMEN
We report a case of anti GBM disease that developed in the renal graft of a patient with Alport syndrome. After reaching abnormal values of creatinine, the patient presented with deteriorating renal function three months after a cadaver transplant and the biopsy showed crescent formation, and linear IF deposits. Circulating antibodies against alpha 5 chain of type IV collagen were found and plasmaphereses stabilized the condition for one year until a lung infection led to withdrawal of the immunosuppressive drugs and the patient returned to dialysis. We discuss the possible mechanisms underlying the specificity of the circulating antibodies in this case, which differs from the target characteristic of the idiopathic form of anti GBM disease, the alpha 3 (IV) chain.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular/etiología , Trasplante de Riñón/efectos adversos , Nefritis Hereditaria/cirugía , Adulto , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Rechazo de Injerto , Humanos , Masculino , PlasmaféresisAsunto(s)
Arabidopsis/enzimología , Fosfoproteínas Fosfatasas/genética , Anticuerpos/inmunología , Arabidopsis/genética , Clonación Molecular , Sondas de ADN , Escherichia coli , Genoma de Planta , Fosfoproteínas Fosfatasas/análisis , Fosfoproteínas Fosfatasas/inmunología , Reacción en Cadena de la Polimerasa/métodos , Proteína Fosfatasa 2 , Proteínas Recombinantes/análisisRESUMEN
The plant Arabidopsis thaliana contains five isoforms of the catalytic subunit of protein phosphatase 2A (PP2A) that can be grouped into two families, one composed by isoforms PP2A-1, -2 and -5 and the other composed by isoforms PP2A-3 and PP2A-4. An Arabidopsis genomic library was screened and several clones corresponding to genes PP2A-3 and PP2A-4 were isolated and analysed. Both genes span over approximately 4.5kbp and are composed of 11 exons and 10 introns that show identical organization. Their untranslated regions are also highly conserved, suggesting that the two genes derive from a common ancestral gene. However, the position of intron/exon junctions completely differs from that of the human PP2A genes. Two transcription start sites have been found in the PP2A-3 gene, the major one mapping at nucleotide position -188 from the translation start codon, whereas only one is observed in PP2A-4 (-145). Functional gene promoter analysis reveals that elements required for transient expression of PP2A-3 and PP2A-4 on a protoplast system are contained within a region of about 600bp upstream from the transcription start sites. This is the first report on the cloning and characterization of genes encoding catalytic subunits of Ser/Thr protein phosphatases 2A in higher plants.
Asunto(s)
Arabidopsis/enzimología , Arabidopsis/genética , Fosfoproteínas Fosfatasas/biosíntesis , Fosfoproteínas Fosfatasas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Clonación Molecular , Cartilla de ADN , Exones , Genes de Plantas , Biblioteca Genómica , Humanos , Intrones , Isoenzimas/biosíntesis , Isoenzimas/química , Isoenzimas/genética , Sustancias Macromoleculares , Datos de Secuencia Molecular , Fosfoproteínas Fosfatasas/química , Reacción en Cadena de la Polimerasa , Proteína Fosfatasa 2 , Protoplastos , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Mapeo Restrictivo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Transcripción GenéticaRESUMEN
We have recently reported the existence of multiple isoforms of the catalytic subunit of protein phosphatase 2A (PP2A) in Arabidopsis thaliana and the molecular cloning of cDNAs encoding three of these proteins (PP2A-1, PP2A-2, PP2A-3). The reported cDNA encoding PP2A-3 was truncated at the 5' terminus, lacking a short fragment of the N-terminal coding sequence. We have now isolated a near full-length cDNA encoding the entire PP2A-3 protein (313 residues). The clone includes 188 nucleotides of 5'-untranslated region, where a 44 bp long poly(GA) track is found. We also describe the cloning of a cDNA encoding a fourth isoform of PP2A (PP2A-4). The polypeptide contains 313 residues being 98% identical to PP2A-3 and only 80% identical to both PP2A-1 and PP2A-2. The mRNA for PP2A-4 is 1.4 kb in length and, although predominantly expressed in roots, it is also found in other organs. It is concluded that in A. thaliana the isoforms of PP2A can be grouped in two extremely conserved subfamilies.