RESUMEN
BACKGROUND: The beneficial effect of biofeedback therapy (BFT) over a period of more than 2 years has not been studied in a large group of patients. The aim of this study was to evaluate the long-term efficacy of BFT for dyssynergic defecation (DD). METHODS: We evaluated the results for 347 consecutive constipated patients with DD who underwent BFT for a median of five sessions between 2004 and 2009. Initial responses were assessed immediately after the completion of BFT. A responder was defined as a subject with at least a three-point improvement from before to after BFT on an 11-point global bowel satisfaction (GBS) scale, or a two-point improvement if the baseline GBS was more than six points. The probability of remaining a responder was estimated by non-parametric maximum likelihood estimation. KEY RESULTS: The initial response rate to BFT was 72.3% (n = 251), Parkinson's disease and higher baseline GBS scores were associated with initial non-response. The long-term efficacy of BFT was analyzed in 103 patients who were followed up for more than 6 months; the initial effects of BFT were maintained in 85 of the patients (82.5%) during a median of 44 months of follow-up (IQR = 12-68). The probability of remaining a responder was 60% at 2 years, and 58% at 5 years. CONCLUSIONS & INFERENCES: The efficacy of BFT is maintained for more than 2 years after BFT in a considerable proportion of constipated patients with DD. BFT is effective and durable treatment for managing DD.
Asunto(s)
Ataxia/terapia , Biorretroalimentación Psicológica/métodos , Estreñimiento/terapia , Anciano , Canal Anal , Estudios de Cohortes , Defecación , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Manometría , Persona de Mediana Edad , Recto , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Puntos de Acupuntura , Acupuntura/métodos , Electrofisiología , Respuesta Galvánica de la Piel/fisiología , Modelos Biológicos , Fenómenos Fisiológicos de la Piel , Adulto , Simulación por Computador , Capacidad Eléctrica , Impedancia Eléctrica , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The human DNA topoisomerase III (hTOP3) gene encodes a topoisomerase homologous to the Escherichia coli DNA topoisomerase I subfamily. To understand the mechanisms responsible for regulating hTOP3 expression, we have cloned the 5'-flanking region of the gene coding for the hTOP3 and analyzed its promoter activity. The presence of a single transcription initiation site was suggested by primer extension analysis. The hTOP3 gene promoter is moderately high in GC content and lacks a canonical TATA box, suggesting that hTOP3 promoter has overall similarity to promoters of a number of housekeeping genes. Examination of the promoter sequence indicated the presence of four Sp-1 consensus binding sequences and a putative initiator element surrounding the transcription initiation site. Transient expression of a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the 52-base pair region from -326 to -275 upstream of the transcription initiation site includes a positive cis-acting element(s) for the efficient expression of hTOP3 gene. On the basis of gel mobility shift and supershift assays, we demonstrated that both YY1 and USF1 transcription factors can bind to the 52-base pair region. When HeLa cells were transiently transfected with a mutant construct which had disabled both YY1- and USF1-binding sites, the luciferase activity was greatly reduced, suggesting that these binding elements play a functional role in the basal activation of the hTOP3 promoter. Transfection studies with mutations that selectively impaired YY1 or USF1 binding suggested that both YY1 and USF1 function as activators in the hTOP3 promoter.