RESUMEN
Economic evaluations of clinical treatments most commonly take the form of cost effectiveness or cost utility analyses. This is appropriate since the main-sometimes the only-benefit of such interventions is increased health. The majority of economic evaluations in public health, however, have also been assessed using these techniques when arguably cost benefit analyses would in many cases have been more appropriate, given its ability to take account of nonhealth benefits as well. An examination of the nonhealth benefits from a sample of studies featured in a recent review of economic evaluations in public health illustrates how overfocusing on cost effectiveness/cost utility analyses may lead to forgoing potential social welfare gains from programmes in public health. Prior to evaluation, programmes should be considered in terms of the potential importance of nonhealth benefits and where these are considerable would be better evaluated by more inclusive economic evaluation techniques.
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Medicina Basada en la Evidencia/economía , Investigación sobre Servicios de Salud/métodos , Salud Pública/economía , Bienestar Social/economía , Análisis Costo-Beneficio , Costos y Análisis de Costo , Humanos , Años de Vida Ajustados por Calidad de Vida , Reino UnidoAsunto(s)
Atención a la Salud/organización & administración , Enfermedades Gastrointestinales/terapia , Hepatopatías/terapia , Enfermedad Aguda , Adolescente , Adulto , Anciano , Atención Ambulatoria/estadística & datos numéricos , Enfermedad Crónica , Consultores , Costo de Enfermedad , Atención a la Salud/normas , Medicina Familiar y Comunitaria/estadística & datos numéricos , Femenino , Gastroenterología , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/mortalidad , Política de Salud , Fuerza Laboral en Salud , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Hepatopatías/etiología , Hepatopatías/mortalidad , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Enfermeras y Enfermeros/provisión & distribución , Aceptación de la Atención de Salud/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Medicina Estatal/organización & administración , Reino Unido/epidemiología , Listas de EsperaRESUMEN
OBJECTIVES: To estimate the feasibility, utility and resource implications of electronically captured routine data for health technology assessment by randomised controlled trials (RCTs), and to recommend how routinely collected data could be made more effective for this purpose. DATA SOURCES: Four health technology assessments that involved patients under care at five district general hospitals in the UK using four conditions from distinct classical specialties: inflammatory bowel disease, obstructive sleep apnoea, female urinary incontinence, and total knee replacement. Patient-identifiable, electronically stored routine data were sought from the administration and clinical database to provide the routine data. REVIEW METHODS: Four RCTs were replicated using routine data in place of the data already collected for the specific purpose of the assessments. This was done by modelling the research process from conception to final writing up and substituting routine for designed data activities at appropriate points. This allowed a direct comparison to be made of the costs and outcomes of the two approaches to health technology assessment. The trial designs were a two-centre randomised trial of outpatient follow-up; a single-centre randomised trial of two investigation techniques; a three-centre randomised trial of two surgical operations; and a single-centre randomised trial of perioperative anaesthetic intervention. RESULTS: Generally two-thirds of the research questions posed by health technology assessment through RCTs could be answered using routinely collected data. Where these questions required analysis of NHS resource use, data could usually be identified. Clinical effectiveness could also be judged, using proxy measures for quality of life, provided clinical symptoms and signs were collected in sufficient detail. Patient and professional preferences could not be identified from routine data but could be collected routinely by adapting existing instruments. Routine data were found potentially to be cheaper to extract and analyse than designed data, and they also facilitate recruitment as well as have the potential to identify patient outcomes captured in remote systems that may be missed in designed data collection. The study confirmed previous evidence that the validity of routinely collected data is suspect, particularly in systems that are not under clinical and professional control. Potential difficulties were also found in identifying, accessing and extracting data, as well as in the lack of uniformity in data structures, coding systems and definitions. CONCLUSIONS: Routine data have the potential to support health technology assessment by RCTs. The cost of data collection and analysis is likely to fall, although further work is required to improve the validity of routine data, particularly in central returns. Better knowledge of the capability of local systems and access to the data held on them is also essential. Routinely captured clinical data have real potential to measure patient outcomes, particularly if the detail and precision of the data could be improved.
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Recolección de Datos/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Proyectos de Investigación/estadística & datos numéricos , Evaluación de la Tecnología Biomédica/métodos , Artroplastia de Reemplazo de Rodilla , Sesgo , Transfusión de Sangre Autóloga , Estudios de Factibilidad , Humanos , Enfermedades Inflamatorias del Intestino/terapia , Reproducibilidad de los Resultados , Apnea Obstructiva del Sueño/terapia , Evaluación de la Tecnología Biomédica/estadística & datos numéricos , Incontinencia Urinaria/terapiaRESUMEN
An economic sub-study was run alongside a large multi-centre randomised trial (MRC-CR06) comparing three chemotherapy regimens; de Gramont, Lokich and raltitrexed in patients with metastatic colorectal cancer. Patients in six of 45 centres in the main trial were approached to take part in the sub-study. Chemotherapy delivery costs were assessed in each sub-study centre with external validity verified by questionnaire to all other centres. Patient representativeness was assessed. Stochastic resource use data, including patient borne costs and non-hospital health service resource use were monitored prospectively. Mean total societal costs were de Gramont= 5051 pounds sterling (s.d. 1910 pounds sterling ), raltitrexed= 2616 pounds sterling (s.d. 991 pounds sterling ) and Lokich= 2576 pounds sterling (s.d. 1711 pounds sterling ). In pairwise comparisons, statistically significant mean total cost differences were shown for de Gramont vs Lokich (mean difference= 2475 pounds sterling , 95%CI 914 pounds sterling - 4037 pounds sterling , P<0.01) and for de Gramont vs raltitrexed (mean difference= 2435 pounds sterling, 95%CI 922 pounds sterling - 2948 pounds sterling , P<0.01). Sensitivity analyses showed little effect on overall costs. The main trial showed de Gramont and Lokich to be equally effective in terms of survival, quality of life and response rates but Lokich had higher toxicity and hand-foot syndrome. Raltitrexed showed similar response rates and overall survival but increased toxicity and inferior quality of life making it a clinically inferior regimen despite its ease of administration and costs. For a comparable clinical outcome, Lokich can be administered for approximately half the cost of de Gramont.
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Antineoplásicos/economía , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/economía , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/patología , Costos y Análisis de Costo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Sensibilidad y Especificidad , Resultado del Tratamiento , Reino UnidoRESUMEN
OBJECTIVE: To evaluate the use of a multidisciplinary record held by patients with cancer in the community. DESIGN: Pragmatic randomised controlled trial. SETTING: The environs of Swansea in south west Wales. PARTICIPANTS: 501 patients under the care of the Department of Oncology, Singleton Hospital, Swansea. INTERVENTION: A patient held record used by the patient and healthcare professionals. Main outcome measures-Health related quality of life (EORTC QLQ-C30) measured at entry into the study and at 6 months; patients' views at 6 months; healthcare professionals' views collected after the completion of patient follow up; NHS resource and booklet use. RESULTS: 1148 patients were eligible for the study; 501 were recruited (44%) and 344 completed the study (172 in each group). There was no significant difference between the two groups in change in quality of life or NHS resource use. The patient held record did not have an impact on communication but was significantly helpful to patients in preparing for appointments, reducing difficulties in monitoring their own progress, and helping them to feel more in control (p<0.05). Fifty three percent of patients would have preferred not to have a patient held record. There was a low level of use of the record by healthcare professionals but most of those who remembered using it indicated that they would prefer patients to have it. CONCLUSIONS: The patient held record is valued by some patients and professionals but has no significant impact on the quality of life of patients or NHS resource use. It has a positive impact on quality by helping patients feel more in control and prepare for meetings with healthcare staff. Patients who find it useful tend to be younger and have more professionals involved in their care. It is recommended that it should be made available to patients on request and used by them according to need.
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Continuidad de la Atención al Paciente/organización & administración , Registros Médicos , Neoplasias/terapia , Servicio de Oncología en Hospital/organización & administración , Participación del Paciente , Satisfacción del Paciente/estadística & datos numéricos , Adolescente , Adulto , Anciano , Actitud del Personal de Salud , Humanos , Persona de Mediana Edad , Evaluación de Procesos, Atención de Salud , Calidad de Vida , Autoeficacia , Medicina Estatal/estadística & datos numéricos , GalesRESUMEN
Market disciplines and incentives were expected to improve efficiency in the UK National Health Service following the introduction of an 'internal market' in 1991. An exploratory survey of all Health Authorities and Trusts in the UK was undertaken to investigate whether players in the NHS managed market are behaving as economic theory predicts they should. The focus was on how and to what extent marginal costing has been used in the contracting process and on whether in some instances an inappropriate use of marginal costing may be resulting in inappropriate investment decisions. Twenty of 29 responding Health Authorities (69%) and 16 of 39 Trusts (41%) stated that they had considered purchasing/providing services on a marginal-cost basis and all of these led to contracts. Marginal-cost contracting appears to be fairly commonplace and the process does not appear to be causing insurmountable conflicts between players. Most marginal-cost contracts were specifically to meet waiting-list initiative targets. Overall results suggest that economic principles are not being particularly adhered to, with expansion in output rarely being related to available capacity. As increased responsibility for commissioning passes to primary care teams and local health groups, there are lessons for those involved in this more disaggregated approach to service shaping and service delivery.
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Servicios Contratados/economía , Asignación de Costos/métodos , Sector de Atención de Salud , Privatización/economía , Medicina Estatal/organización & administración , Ambulancias/economía , Servicios de Salud Comunitaria/economía , Toma de Decisiones en la Organización , Competencia Económica , Eficiencia Organizacional , Investigación sobre Servicios de Salud , Hospitales Públicos/economía , Competencia Dirigida , Medicina Estatal/economía , Encuestas y Cuestionarios , Reino UnidoRESUMEN
Retinitis pigmentosa (RP), an inherited retinal degenerative disease causing blindness, is characterized by progressive apoptotic death of photoreceptors. Therapeutic modification of photoreceptor apoptosis may provide an effective therapy for this disorder. Ciliary neurotrophic factor (CNTF) has been shown to promote survival of a number of different neuronal cell types, including photoreceptors. The present study aimed to test whether adeno-associated virus (AAV)-mediated delivery of the gene encoding CNTF delays photoreceptor death in the rhodopsin knockout (opsin(-/-)) mouse, an animal model of RP. The vector was made to express a secretable form of CNTF in tandem with a marker GFP. Cultured 293 cells transduced with this virus expressed both CNTF and GFP. The conditioned media from such cells supported the survival of chick dorsal root ganglion neurons in the same manner as recombinant CNTF. Subretinal administration of this virus led to efficient transduction of photoreceptors as indicated by GFP fluorescence and CNTF immunostaining. Histologic examination showed significant photoreceptor preservation in the injected quadrant of the retina. This protection lasted through termination of the experiment (3 months). AAV-mediated delivery of CNTF may have implications for the treatment of human retinal degeneration.
Asunto(s)
Factor Neurotrófico Ciliar/genética , Dependovirus/genética , Técnicas de Transferencia de Gen , Células Fotorreceptoras de Vertebrados/fisiología , Rodopsina/genética , Animales , Animales Recién Nacidos , Bioensayo , Western Blotting , Línea Celular , Supervivencia Celular , Células Cultivadas , Embrión de Pollo , Ensayo de Inmunoadsorción Enzimática , Genes Reporteros , Vectores Genéticos , Proteínas Fluorescentes Verdes , Humanos , Inmunohistoquímica , Proteínas Luminiscentes/metabolismo , Ratones , Ratones Noqueados , Microscopía Fluorescente , Mutagénesis Insercional , Neuronas/metabolismo , Sistemas de Lectura Abierta , Retina/metabolismo , Retinitis Pigmentosa/terapia , Factores de Tiempo , Transducción GenéticaRESUMEN
OBJECTIVE: To evaluate the association between specific histologic features and cytogenetic abnormalities in ectopic pregnancies. DESIGN: Blinded histologic analysis. SETTING: University hospital. PATIENT(S): Fifty-four patients with ectopic pregnancy for whom successful karyotypes and sufficient histologic material were available. INTERVENTION(S): Histologic evaluation of chorionic villi from ectopic pregnancies was done by two pathologists who were unaware of the cytogenetic outcome. Seventeen histologic features were evaluated: villus size, villus contour, ghost villi, hydropic villi, trophoblastic hyperplasia, trophoblastic hypoplasia, syncytial knots, Hofbauer cells, blood vessels, trophoblastic lacunae, trophoblastic inclusions or cisterns, degeneration, fibrohyalinization, microcalcifications, and perivillous and intervillous fibrin deposits. MAIN OUTCOME MEASURE(S): The association between histopathologic features and cytogenetic outcome. RESULT(S): The presence of ghost villi and intervillous or perivillous fibrin was found to be associated with cytogenetic abnormalities. These features are associated with previous fetal cell death. CONCLUSION(S): This study does not support an association between specific histologic features of chorionic villi and cytogenetic abnormalities in ectopic pregnancies. The only histologic features that were associated with cytogenetic abnormalities (i.e., ghost villi and intervillous and perivillous fibrin) are merely a result of previous fetal cell death.
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Aberraciones Cromosómicas , Trastornos de los Cromosomas , Análisis Citogenético , Embarazo Ectópico/genética , Embarazo Ectópico/patología , Adolescente , Adulto , Vellosidades Coriónicas/metabolismo , Vellosidades Coriónicas/patología , Aberraciones Cromosómicas/metabolismo , Femenino , Fibrina/metabolismo , Humanos , Ploidias , EmbarazoRESUMEN
The feasibility of reliably measuring clitoral blood flow using standard color Doppler ultrasonography was evaluated by two independent assessors in a sample of 40 pre- and post-menopausal women. High positive correlations with no significant mean differences between examiners were found for three major standard blood flow measures including maximum velocity, resistance, and pulsatility indices. With further methodological refinements, ultrasonographic evaluation of clitoral blood flow will be adaptable for clinical and research use and is likely to become the standard physiological measure of female sexual arousal.
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Clítoris/irrigación sanguínea , Clítoris/diagnóstico por imagen , Conducta Sexual/psicología , Ultrasonografía Doppler en Color/métodos , Adulto , Nivel de Alerta/fisiología , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia/fisiologíaRESUMEN
Members of the Drosophila Iroquois homeobox gene family are implicated in the development of peripheral nervous system and the regionalization of wing and eye imaginal discs. Recent studies suggest that Xenopus Iroquois homeobox (Irx) genes are also involved in neurogenesis. Three mouse Irx genes, Irx1, Irx2 and Irx3, have been previously identified and are expressed with distinct spatio-temporal patterns during neurogenesis. We report here the cloning and expression analysis of two novel mouse Irx genes, Irx5 and Irx6. Although Irx5 and Irx6 proteins are structurally more related to one another, we find that Irx5 displays a developmental expression pattern strikingly similar to that of Irx3, whereas Irx6 expression resembles that of Irx1. Consistent with the notion that Mash1 is a putative target gene of the Irx proteins, all four Irx genes display an overlapping expression pattern with Mash1 in the developing CNS. In contrast, the Irx genes and Mash1 are expressed in complementary domains in the developing eye and olfactory epithelium.
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Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Neuronas/fisiología , Factores de Transcripción/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Complementario , Ratones , Datos de Secuencia Molecular , Homología de Secuencia de AminoácidoRESUMEN
OBJECTIVE: To evaluate whether follow up of patients with inflammatory bowel disease is better through open access than by routine booked appointments. DESIGN: Pragmatic randomised controlled trial. SETTING: Two district general hospitals in Swansea and Neath, Wales. PARTICIPANTS: 180 adults (78 with Crohn's disease, 77 ulcerative or indeterminate colitis, 25 ulcerative or idiopathic proctitis) recruited from outpatient clinics during October 1995 to November 1996. INTERVENTION: Open access follow up according to patient need. MAIN OUTCOME MEASURES: Generic (SF-36) and disease specific (UK inflammatory bowel disease questionnaire UKIBDQ) quality of life, number of primary and secondary care contacts, total resource use, and views of patients and general practitioners. RESULTS: There were no differences in generic or disease specific quality of life. Open access patients had fewer day visits (0.21 v 0. 42, P<0.05) and fewer outpatient visits ( 4.12 v 4.64, P<0.01), but some patients had difficulty obtaining an urgent appointment. There were no significant differences in specific investigations undertaken, inpatient days, general practitioner surgery or home visits, drugs prescribed, or total patient borne costs. Mean total cost in secondary care was lower for open access patients (P<0.05), but when primary care and patient borne costs were added there were no significant differences in total costs to the NHS or to society. General practitioners and patients preferred open access. CONCLUSIONS: Open access follow up delivers the same quality of care as routine outpatient care and is preferred by patients and general practitioners. It uses fewer resources in secondary care but total resource use is similar. Better methods of ensuring urgent access to outpatient clinics are needed.
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Enfermedades Inflamatorias del Intestino/terapia , Adulto , Atención Ambulatoria/economía , Actitud del Personal de Salud , Análisis Costo-Beneficio , Estudios de Seguimiento , Recursos en Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud , Hospitales de Distrito , Humanos , Enfermedades Inflamatorias del Intestino/economía , Satisfacción del Paciente , Guías de Práctica Clínica como Asunto , Calidad de Vida , Reino UnidoRESUMEN
OBJECTIVES: We aimed to show how in multi-disciplinary research data collected to meet the needs of one discipline can provide information of value to another. METHODS: Using the critical incident technique, 25 GPs were interviewed about recent scans requested for patients with knee and lumbar spine complaints. Transcripts of the interviews were scrutinized from both a medical and an economic perspective. RESULTS: Five key economic issues where further research is needed were identified. CONCLUSIONS: The total value of the information provided by multi-disciplinary research may exceed the sum of the information collected to meet the requirements of the individual disciplines.
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Conducta Cooperativa , Medicina Familiar y Comunitaria , Relaciones Interprofesionales , Imagen por Resonancia Magnética/economía , Dolor/patología , Investigación , Inglaterra , Humanos , Entrevistas como AsuntoRESUMEN
The major components of transcription factor AP-1 (Activator Protein 1) are encoded by the two families of genes related to the proto-oncogenes c-fos and c-jun. The fos-related antigen-2 (fra-2) gene is the most recently described member of the Fos family. To determine the oncogenic potential of fra-2, transgenic mice were generated which over-express fra-2 in a number of tissues. No tumours were evident in any transgenic mice up to 18 months of age, although eye development was severely disrupted in these animals. Corneal abnormalities could be observed histologically as early as embryonic day 15.5 and eyelid fusion failed to occur. Adult eyes were characterized by generalized anterior segment dysgenesis similar to that previously reported in transgenic mice over-expressing transforming growth factor alpha (TGF alpha), and occasionally microphthalmia. Expression of fra-2 was shown to increase following TGF alpha treatment of cells in vitro, suggesting that AP-1 complexes containing Fra-2 contribute to TGF alpha signalling events.
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Proteínas de Unión al ADN/genética , Anomalías del Ojo/genética , Ojo/crecimiento & desarrollo , Factores de Transcripción/genética , Transgenes/genética , Células 3T3/citología , Células 3T3/efectos de los fármacos , Células 3T3/metabolismo , Animales , Constitución Corporal/genética , Proteínas de Unión al ADN/efectos de los fármacos , Ojo/metabolismo , Ojo/patología , Anomalías del Ojo/embriología , Anomalías del Ojo/patología , Antígeno 2 Relacionado con Fos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/genética , Histocitoquímica , Ratones , Ratones Transgénicos , Fenotipo , Regiones Promotoras Genéticas/genética , Factores de Transcripción/efectos de los fármacos , Factor de Crecimiento Transformador alfa/farmacología , Transgenes/efectos de los fármacosRESUMEN
The mechanisms regulating the development and function of the immune system are diverse and complicated. The signaling pathways and target genes that become activated upon cell-surface stimulation are currently being defined, and transcription factor activator protein 1 (AP-1) is proving to be an important regulator of nuclear gene expression in leukocytes. In vitro and in vivo studies have demonstrated that AP-1 expression is induced after a diverse range of stimuli and that AP-1 contributes to the regulation of a large number of genes. In this review we will examine the role of AP-1 during leukocyte activation and differentiation in the immune system.
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Linfocitos B/fisiología , Receptores de Antígenos de Linfocitos B/fisiología , Receptores de Antígenos de Linfocitos T/fisiología , Linfocitos T/fisiología , Factor de Transcripción AP-1/fisiología , Animales , Formación de Anticuerpos , Apoptosis , Diferenciación Celular , Citocinas/genética , Regulación del Desarrollo de la Expresión Génica , Humanos , Activación de Linfocitos , Unión Proteica , Transducción de Señal , Timo/citología , Transcripción GenéticaRESUMEN
Arrythmogenic right ventricular dysplasia (ARVD) is an autosomal dominant inherited cardiomyopathy with incomplete penetrance and variable expressivity. Recently, the gene was mapped to 14q23-24. It is being increasingly investigated as a major cause of sudden death at a young age. Anterior polar cataract (APC) is a rare hereditary form of lens opacity. The locus for an APC gene was located tentatively on 14q24qter. We describe a patient with a severe form of ARVD in whom asymptomatic APC was detected by an ophthalmologic examination. His sister had ARVD and similar cataracts. Parents were second cousins but were healthy. This is the first report of possible autosomal recessive inheritance of ARVD. This is also the first time that the combination of ARVD and APC is reported. Three possibilities may explain this concurrence: pleiotropy, contiguous gene syndrome, or coincidence. Our findings suggest placement of an APC gene at 14q23-24.
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Displasia Ventricular Derecha Arritmogénica/complicaciones , Catarata/complicaciones , Adulto , Displasia Ventricular Derecha Arritmogénica/genética , Catarata/genética , Cromosomas Humanos Par 14/genética , Consanguinidad , Femenino , Genes Recesivos , Humanos , MasculinoRESUMEN
OBJECTIVE: To compare biopsychologic profiles of women with dyspareunia with a matched no-pain control sample, and to determine whether dyspareunia subtypes based on physical findings have different psychosocial profiles from matched controls. METHODS: One hundred and five women with dyspareunia and 105 matched no-pain control women underwent standard gynecologic examination, endovaginal ultrasound, and colposcopy. They also completed a structured interview inquiring about pain other than dyspareunia, sexual function, and history of abuse, the Brief Symptom Inventory, the Sexual Opinion Survey, and the Locke-Wallace Marital Adjustment Scale. RESULTS: In comparison with women who do not experience pain with intercourse, the dyspareunia sample was found to have more physical pathology on examination, and they reported more psychologic symptomatology, more negative attitudes toward sexuality, higher levels of impairment in sexual function, and lower levels of marital adjustment. They did not report more current or past physical or sexual abuse. However, when the undifferentiated dyspareunia sample was divided into subtypes based on physical findings from the gynecologic examinations, the pattern of significant differences from controls varied according to dyspareunia subtype. Elevated psychologic symptomatology and relationship maladjustment were confined to the subtype with no discernible physical findings who reported levels of sexual function not significantly different from matched controls. The vulvar vestibulitis subtype suffered the highest levels of sexual impairment, although this subtype was not characterized by higher levels of psychologic symptoms than controls. CONCLUSION: As an undifferentiated group, women with dyspareunia have more physical pathology, psychologic distress, sexual dysfunction, and relationship problems. However, this pattern of differences appears to vary depending on the presence and type of physical findings evident on examination. Dyspareunia is a heterogeneous disorder requiring comprehensive gynecologic and psychosocial assessment to determine differentiated treatment strategies.
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Dispareunia/patología , Dispareunia/psicología , Adulto , Anciano , Femenino , Humanos , Libido , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
An important first step in the chromatin remodelling process is the initial binding of a transcriptional activator to a nucleosomal template. We have investigated the ability of Fos/Jun (a transcriptional activator involved in the signal transduction pathway) to interact with its cognate binding site located in the promoter region of the mouse fos-related antigen-2 (fra-2) promoter, when this site was reconstituted into a nucleosome. Two different nucleosome assembly systems were employed to assemble principally non-acetylated or acetylated nucleosomes. The ability of Fos/Jun to interact with an acetylated or an unacetylated nucleosome differed markedly. Fos/Jun bound to an unacetylated nucleosome with only a 4- to 5-fold reduction in DNA binding affinity compared with naked DNA. Strikingly, the binding of Fos/Jun to a single high-affinity site incorporated into an acetylated nucleosome resulted in the complete disruption of nucleosomal structure without histone displacement. Moreover, this disruption was sufficient to facilitate the subsequent binding of a second transcription factor.