RESUMEN
A significant proportion of transplant patients undergoing immunosuppressant therapy experience gastrointestinal (GI) symptoms. The SIGIT-QoL is a brief instrument developed to measure adverse gastrointestinal effects on patients' health-related quality of life (HRQoL). The goal of this study was to analyze the psychometric properties of the SIGIT-QoL that are required for its use in clinical research and practice, especially its value for detecting changes in the impact of gastrointestinal symptoms on HRQoL of solid organ transplant (SOT) recipients. To this end, an observational, multicenter, prospective study was conducted. SOT patients aged ≥18 years who had received the graft 3 to 24 months before and were experiencing gastrointestinal symptoms were evaluated at baseline, 1 to 2 weeks later, and 3 months after baseline. Sociodemographic and clinical data recorded included: age, sex, SOT type (lung, kidney, liver, or heart), acute allograft rejection, gastrointestinal etiology, Clinical Global Impressions (CGI) and Patient Global Impression (PGI) Severity of Illness (SI) and Global Improvement (GI) scores, and the SIGIT-QoL (scores range from 0 [maximum impact] to 68 [minimum disruption]). Intraclass correlation coefficients, differences between baseline and last visit (Wilcoxon test), effect size (Cohen's d), the minimal important differences (using CGI and PGI scores as anchors in General Linear Models), and the cutoff score (receiver-operating characteristic analysis) were calculated. In total, 277 SOT patients (61.4% male) were included. Mean ± SD age was 52.69 ± 11.65 years, time since transplantation was 12.31 ± 6.74 months, and 22.4% experienced an acute allograft rejection. At baseline, total SIGIT-QoL mean scores (51.21 ± 11.25) showed an impact on patients' HRQoL that was diminished 3 months later (57.40 ± 8.38; P < .001). SIGIT-QoL test-retest reliability was adequate (intraclass correlation coefficient, 0.740-0.895). A moderate effect size (d = -0.550) was found. Moreover, a minimal important difference of 4.2 points in total scores was found (F4,223 = 16.917 [P < .001] and F4,224 = 25.138 [P < .001]). Finally, a cutoff point (55.00 points) was estimated (area under the concentration-time curve, 0.846 [95% confidence interval, 0.798-0.894], P < .001; sensitivity, 0.793; specificity, 0.713; negative likelihood ratio, 0.290; positive likelihood ratio, 2.762). We concluded that the SIGIT-QoL is a feasible (average completion time, <6.5 minutes), reliable, and valid instrument for assessing the impact of gastrointestinal symptoms on the HRQoL of SOT patients.
Asunto(s)
Enfermedades Gastrointestinales/psicología , Trasplante de Órganos/efectos adversos , Calidad de Vida , Receptores de Trasplantes , Anciano , Femenino , Enfermedades Gastrointestinales/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Advagraf is a new modified-release once-daily formulation of tacrolimus with a similar efficacy and safety profile to twice-daily tacrolimus (Prograf) according to clinical trials. Few data are published about its use in clinical practice, outside of sponsored clinical trials. We compared efficacy and basic pharmacokinetics of once-daily and twice-daily tacrolimus in de novo renal transplantation. METHODS: The Advagraf group included 26 de novo renal cases who had received initial immunosuppression with once-daily tacrolimus (0.2 mg/kg from day 1 posttransplantation) combined with mycophenolic acid, steroids, and anti-CD25 monoclonal antibodies (2 doses). We compared them with a Prograf group of 26 transplants performed immediately before, who received equivalent immunosuppression with twice-daily tacrolimus (0.2 mg/kg from day 1). RESULTS: We did not observe significant differences between groups in demographics, efficacy, and basic pharmacokinetics, namely, tacrolimus trough levels at 7, 15, 30, 60, or 90 days. We found that recipients on Advagraf needed significantly higher tacrolimus doses per kg up to 6 months post-transplantation than those on Prograf: 0.16 vs 0.11; 0.14 vs 0.08; and 0.12 vs 0.08 mg/kg at 1, 3, and 6 months. No patient suffered severe liver dysfunction. There were no differences between groups in the administration of drugs interacting with CYP3A4 or prokinetics, which could alter tacrolimus pharmacokinetics. CONCLUSIONS: Among de novo renal cases, the new once-daily formulation of tacrolimus offered a similar short-term efficacy profile as the twice-daily tacrolimus. But it was necessary to use up to a 50% higher dose of Advagraf than Prograf to achieve similar trough levels during the first 6 months.
Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Sirolimus/análogos & derivados , Tacrolimus/uso terapéutico , Anciano , Anticuerpos Monoclonales/sangre , Relación Dosis-Respuesta a Droga , Everolimus , Femenino , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/farmacocinética , Subunidad alfa del Receptor de Interleucina-2/inmunología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Sirolimus/farmacocinética , Sirolimus/uso terapéutico , Tacrolimus/farmacocinéticaAsunto(s)
Antivirales/uso terapéutico , Virus BK , Citosina/análogos & derivados , Trasplante de Riñón/efectos adversos , Nefritis Intersticial/tratamiento farmacológico , Nefritis Intersticial/virología , Organofosfonatos/uso terapéutico , Infecciones por Polyomavirus/etiología , Probenecid/uso terapéutico , Infecciones Tumorales por Virus/etiología , Adulto , Cidofovir , Citosina/uso terapéutico , Quimioterapia Combinada , Humanos , MasculinoRESUMEN
BACKGROUND: IgA nephropathy (IgA) is one of the most common glomerulonephritis. Renal transplantation is the treatment of choice for patients with ESRD due to any kind of glomerulopathy, including IgA and Henoch-Schönlein purpura nephritis (H-SP), but original disease recurrence is now the third most frequent cause of allograft loss. METHODS: Eighty-seven cases of glomerulonephritis as the original disease were divided in two groups: group A--37 affected with 31 IgA and 6 H-SP; and group B--50 with other glomerulopathies. We compared patient and graft survivals at 5 years. To assess the presence of IgA or H-SP recurrence in group A patients, we performed an allograft biopsy in the presence of microhematuria, proteinuria, or an increased plasma creatinine. Known risk factors influencing recurrence rate were also analyzed. RESULTS: Five-year patient (97% vs 95%) and graft survivals (81% vs 78%) were not significantly different between groups A and B. Patients with crescentic glomerulonephritis (CGN) at the moment of diagnosis of IgA or H-SP showed a 5-year graft survival of 71% in contrast with 100% graft survival among those with mesangial or focal and segmental glomerulosclerosis pattern (P = .03). Histological recurrence was diagnosed in eight patients: six IgA and two H-SP. Women (P = .013) and a good HLA match (P = .029) were significantly associated with the risk of recurrence. CONCLUSIONS: When compared with other glomerulonephritis patients, with IgA or S-HP showed similar 5-year graft and patient survivals. Nevertheless, graft survival was shorter among patients with crescentic glomerulonephritis at the moment of diagnosis. Thus, the disease prognosis after grafting may be linked to the initial histological aggressiveness. Women and those patients transplanted with a good HLA match were prone to develop disease recurrence with a tendency toward a lower 5-year graft survival.
Asunto(s)
Glomerulonefritis por IGA/diagnóstico , Vasculitis por IgA/diagnóstico , Trasplante de Riñón/efectos adversos , Adulto , Cadáver , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Trasplante de Riñón/mortalidad , Trasplante de Riñón/fisiología , Donadores Vivos , Masculino , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Donantes de TejidosRESUMEN
BACKGROUND: Hypertension (HT) accounts for nearly 60% to 80% of renal transplant patients (RT). It is one of the most important risk factors for cardiovascular diseases and may cause chronic graft dysfunction. Therefore, it is important to accurately detect and treat HT. We aimed to evaluate the changes in ambulatory blood pressure monitoring (ABPM) parameters among hypertensive RT after active treatment compared with baseline values. METHODS: Thirty seven RT (25 men, 12 women, aged 49.4 +/- 11.2 year) diagnosed with mild to moderate HT underwent 24-hour ABPM after a 4-week washout period (W0). For the 23 RT with confirmed HT of a second 24-hour ABPM was recorded after 4 weeks of treatment with doxazosin GITS (-4 mg once daily in the morning), a new formulation of an alpha1-receptor inhibitor (W4). Nondippers were considered when mean blood pressure (BP) showed a < or = 10% reduction during sleep. Statistical analyses included Saphiro-Wilks test, Student t test, and ANOVA. RESULTS: After active treatment systolic, diastolic, and mean BP (SBP, DBP, MBP) significantly decreased during diurnal and 24 hours but not the nocturnal period. No significant change was observed for heart rate nor for pulse pressure during any period. The prevalence dippers increased from 0% to 17% after treatment. After placebo administration 8 among 37 RT with HT diagnosed according to casual BP remained hypertensive at nighttime (but not at daytime) according to 24-hour ABPM. CONCLUSIONS: Diurnal and 24-hour periods of ABPM showed significant changes in SBP, DBP, and MBP after active treatment with doxazosin GITS. No significant BP changes were observed in the nocturnal period or in dipper status. Further studies using ABPM must be undertaken to determine the optimal dosage and time of administration of antihypertensive drugs in RT.
Asunto(s)
Antihipertensivos/uso terapéutico , Monitoreo Ambulatorio de la Presión Arterial/métodos , Hipertensión/fisiopatología , Trasplante de Riñón/fisiología , Presión Sanguínea , Estudios de Cohortes , Diástole , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Reproducibilidad de los Resultados , SístoleRESUMEN
OBJECTIVE: The objective of this study is to assess a Simulect (basiliximab) regimen in routine clinical practice in the Spanish kidney transplantation units to evaluate efficacy and safety. METHODS: In this prospective, observational study, data on demographics, parameters of efficacy, and safety in patients who under with kidney transplantation treated with Simulect (basiliximab) were collected through an on-line collection system. RESULTS: One hundred sixty three patients at 18 kidney transplant units included 12 months follow-up. The patient mean age was 52 years (DS 13,67) including 96 (58.90%) men and 67 (41.10%) women. Cold ischemia time was 19 hours (DS 6,79). Only 2 patients presented with PRA >50%. For prophylactic immunosuppression, 67.13% of patients received triple therapy with CNI (cyclosporine 49.65% or tacrolimus 17.48%), MMF (66.43%) or AZA (10.49%), and steroids. Incidence of acute rejection (AR) at 12 months was 12.27% (1.84% steroid-resistant). In subgroup analysis, AR was 13.5% in nondiabetics and 4.5% in diabetics, including 3 steroid-resistant episodes (1.84%) in nondiabetics and none in diabetics. In relation to donor age, AR was incidence 10.3% in patients with kidneys from donors aged 50 years or younger and 10.6% when donors were older than 50 years, including 1 (1.73%) and 2 (1.93%) steroid-resistant episodes, respectively. The graft and patient survival rates at 12 months were 90% and 98%, respectively. CONCLUSIONS: Simulect (basiliximab) used in routine clinical practice provided good prophylaxis against acute rejection in several kidney transplant patient populations, similar to that observed in randomized clinical studies with excellent tolerability and safety.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Trasplante de Riñón/inmunología , Proteínas Recombinantes de Fusión , Corticoesteroides/uso terapéutico , Factores de Edad , Basiliximab , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España , Análisis de Supervivencia , Factores de TiempoRESUMEN
UNLABELLED: Posttransplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoid diseases that occur after solid organ and bone marrow transplantation. We performed a retrospective study to assess the incidence, response to treatment, and patient and graft survival after PTLD. PATIENTS: Between January 1980 and December 2002, 1.96% (n=10) of 509 renal transplant recipients developed PTLD. Seventy percent were men. Mean age was 40 years (range 21-65). They were classified into four groups based upon the type of PTLD: group I, early lesion (n=1); group II, polymorphic PTLD (n=1); group III, monomorphic PTLD (n=7) including five non-Hodgkin lymphoma [NHL] and two Burkitt (BL); and group IV, Hodgkin lymphoma (HL) (n=1). The mean time from transplantation to diagnosis was 77 months (range 4-138). Although only 20% of cases were early presentation, Epstein-Barr virus (EBV) was found in the tumor cells of seven cases. Treatment was individualized according to PTLD type: for group I, immunosuppression reduction (IR); group II, IR plus acyclovir; group III, withdrawal or IR plus chemotherapy and/or surgery in all but one patient who was also treated with anti-CD20 monoclonal antibody and radiotherapy. Interferon was also used in one patient. For group IV, treatment was IR plus radiotherapy. RESULTS: A complete response was achieved in nine cases (90%) with one recurrence. Three patients returned to dialysis. One patient with BL died. CONCLUSIONS: The incidence of PTLD in our center was 1.96%. Patient survival after PTLD was 90%, with 60% maintaining allograft function. Individualized treatment according to extension, histology, and location is mandatory to obtain a high survival rate.
Asunto(s)
Supervivencia de Injerto/fisiología , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/epidemiología , Adulto , Anciano , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/mortalidad , Trastornos Linfoproliferativos/clasificación , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Hypertension (HT), a prevalent complication in renal transplant patient (RT), must be accurately treated because cardiovascular disease is the leading cause of death and of chronic graft dysfunction. Sympathetic activity may contribute to HT in RT, yielding the rationale to suspect that doxazosin, an alpha1-adrenergic receptor inhibitor, may lower blood pressure (BP). The aim of this study was to evaluate the efficacy and safety of doxazosin GITS (4 and 8 mg) in RT. METHODS: Twenty-three hypertensive RT received doxazosin 4 mg once daily for 4 weeks (W4) followed by a 4-week washout (W0) and 17/23 treated with doxazosin 8 mg for 4 more weeks (W8) due to persistent HT. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM) after W0, W4, and W8. Laboratory tests were performed, adverse events recorded, and prostatic symptomatology examined. Statistical analysis included Saphiro-Wilks, Student t, ANOVA, Wilcoxon, or Friedman tests. RESULTS: The systolic, diastolic, and mean BP were significantly lowered at W4 in awake (P<.001) and 24 hour period (P<.005) but not sleep recordings. Doxazosin 8 mg had no significant additional effect to lower BP at any period. Normotension was reached in 13% and 21.7% of patients at W4 and W8, respectively. Palpitations were the only reported adverse event after treatment (incidence similar to placebo). There was no significant change in the laboratory values. CONCLUSIONS: Doxazosin (-4 mg) effectively decreased BP in awake and 24-hour periods without a significant improvement during sleep. A double dose of the drug added little benefit. Optimal BP was reached by an insufficient number of patients. Doxazosin proved to have a good tolerance and safe profile. This results suggest that doxazosin should be considered a good add-on treatment to other antihypertensive drugs in RT.
Asunto(s)
Antihipertensivos/uso terapéutico , Doxazosina/uso terapéutico , Hipertensión/tratamiento farmacológico , Trasplante de Riñón/fisiología , Complicaciones Posoperatorias/tratamiento farmacológico , Antagonistas Adrenérgicos alfa/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Doxazosina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , PlacebosRESUMEN
OBJECTIVE: Evaluate the results of Nesbit's technique in patients with Peyronie's disease. METHODS AND MATERIALS: Between 1990 and 2002, 45 patients were treated using the Nesbit's procedure to correct Peyronie's disease curvature. Mean age was 57.6 (range 41-73). Dorso lateral incurvation was the most common. RESULTS: Total correction of the curvature in 40 patients (88%). High grade of satisfaction in 39 patients (86.66%). CONCLUSION: Nesbit's operation is an easy and effective surgical technique in the peyronie's disease for curvature correction.
Asunto(s)
Induración Peniana/cirugía , Adulto , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Urológicos/métodosAsunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Estreptocócicas/administración & dosificación , Vacunación , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Infecciones por VIH/complicaciones , Humanos , Huésped Inmunocomprometido , Lactante , Factores de RiesgoRESUMEN
No disponible
Asunto(s)
Preescolar , Niño , Adolescente , Adulto , Anciano , Lactante , Humanos , Vacunación , Factores de Riesgo , Infecciones por VIH , Huésped Inmunocomprometido , Infecciones Neumocócicas , Vacunas Estreptocócicas , Factores de EdadRESUMEN
INTRODUCTION AND OBJECTIVES: Renal Cell Carcinoma (RCC) represents 3% of all neoplasm. The growing incidental diagnosis of small renal tumor has allowed the application of nephron sparing surgery (NSS), even in those cases with a normal contralateral kidney. We present the results of NSS at our center in the last decade. MATERIAL AND METHODS: A retrospective analysis of all NSS that were made at our center in cases of renal masses. Difference is made between elective surgery (tumors less than 4 cm with a normal contralateral kidney) and obligatory surgery (all other cases). RESULTS: From 1990 since 2000 a total of 65 NSS were made from a total of 436 surgeries for renal tumors (14.9%). In 22 patients NSS was obligatory, while in 43 was elective. Mean (SD) age was 59.1 years (+/- 11.7), mean tumor size 3.4 cm (+/- 1.4), mean hospital staying was 9.2 days (+/- 7). Renal normothermic ischaemia was use during surgery in all cases, with a mean ischaemic time of 25.7 min. Nine tumors (13.8%) were benign. Morbidity: 10.8%. Mortality: 1.5%. The cancer specific survival at 36 months of follow-up (mean 37.4) is 98.4% and global survival is 90.3%. CONCLUSIONS: Nephron Sparing Surgery is a valid alternative in the treatment of RCC, specially for tumors less than 4 cm in diameter and having a normal contralateral kidney; NSS is also an effective technique for patients bearing renal tumors in a solitary kidney.
Asunto(s)
Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Nefrectomía/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The antibiotic puromycin, an inhibitor of protein synthesis, was shown to inhibit vaccinia virus (VV) replication. We evaluated the use of puromycin-resistance (pac) gene as a selectable marker in VV. A recombinant vaccinia virus expressing pac (VV-pac) under the control of a viral early/late promoter was constructed and characterized. VV-pac grew in the presence of puromycin at concentrations that were inhibitory for the parental VV and toxic for the cells. Isolation of recombinant VV usually relies on plaque purification under selective conditions. Because virus plaquing was not feasible under inhibitory puromycin concentration, a protocol based on serial passage of virus was devised. The usefulness of this procedure in selecting pac expressing viruses was tested by isolating a recombinant VV.
Asunto(s)
Farmacorresistencia Microbiana/genética , Puromicina/farmacología , Virus Vaccinia/genética , Animales , Línea Celular , ADN Recombinante , Relación Dosis-Respuesta a Droga , Marcadores Genéticos , Proteínas Fluorescentes Verdes , Proteínas Luminiscentes/genética , Plásmidos/genética , Proteínas Recombinantes de Fusión/genética , Factores de Tiempo , Virus Vaccinia/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
P37 (F13L gene product), the most abundant protein in the envelope of the extracellular virus form of the prototype poxvirus, vaccinia virus (VV), is a crucial player in the process leading to acquisition of the envelope, virus egress and transmission. We have cloned and sequenced a swinepox virus (SPV) gene homologous to VV F13L. The SPV gene product, termed P42, was 54% identical to P37, the VV F13L gene product, and, among the poxviruses, was most similar (73% identity) to the myxoma virus homologue. The SPV P42 gene contained late transcription signals and was expressed only at late times during infection. The protein was palmitylated, and showed an intracellular distribution similar to that of VV P37, both by immunofluorescence and by subcellular fractionation. As with VV P37, SPV P42 was incorporated in extracellular enveloped SPV particles, but was absent from the intracellular mature virus form. To check the ability of SPV P42 to function in the context of VV infection, we inserted the SPV gene into a VV deficient in P37, which is severely blocked in virus envelopment and cell-to-cell transmission. Despite correct expression of SPV P42, the resulting recombinant VV showed no rescue of extracellular virus formation or cell-to-cell virus spread. The lack of function of SPV P42 in the VV genetic background suggests that specific interactions between SPV P42 or VV P37 and other viral proteins is required to drive the envelopment process.
Asunto(s)
Proteínas de la Membrana/genética , Suipoxvirus/genética , Virus Vaccinia/genética , Proteínas del Envoltorio Viral/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia , Homología de Secuencia de AminoácidoAsunto(s)
Suero Antilinfocítico/uso terapéutico , Ciclosporina/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Ácido Micofenólico/análogos & derivados , Enfermedad Aguda , Adulto , Suero Antilinfocítico/efectos adversos , Ciclosporina/efectos adversos , Quimioterapia Combinada , Femenino , Rechazo de Injerto/epidemiología , Humanos , Inmunosupresores/efectos adversos , Incidencia , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéuticoAsunto(s)
Inmunosupresores/efectos adversos , Trasplante de Riñón/fisiología , Ácido Micofenólico/análogos & derivados , Adulto , Creatinina/sangre , Ciclosporina/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Prednisona/uso terapéutico , Proteinuria , Diálisis Renal , Reoperación , Factores de RiesgoRESUMEN
Angiodysplasia (AD) may be the source of bleeding in patients with gastrointestinal hemorrhage, with special occurrence in the elderly population and in patients with chronic renal failure (CRF). Although several techniques have been tested for its diagnosis, the gold standard is not well defined yet. We analyze the usefulness of 99mTc-labelled red blood cell (99mTc RBC) scintigraphy in the localization of bleeding from AD lesions in a cohort of 21 patients. Other investigative methods include fibrocolonoscopy examination, angiography, or diagnostic laparotomy. Group A (AD and CRF): 11 patients. Group B (AD without CRF): 10 patients. 99mTc RBC scintigraphy showed 88.9% sensitivity and specificity in group A, while in group B it had 100% sensitivity and specificity. Arteriography showed 100% sensitivity and specificity. On the contrary, fibrocolonoscopy had a very low sensitivity (30%). Our results suggest that 99mTc RBC scintigraphy may be the preferred diagnostic tool for AD, especially in patients with CRF, in whom arteriography may accelerate the decline of renal function.