RESUMEN
This paper presents a short review of data supporting a dexamethasone sparing regimen, SEC, to reduce glioblastoma related brain edema. The conclusion of the reviewed data is that the rationale and risk/benefit ratio favors a pilot study to determine if the three drug regimen of SEC can reduce need for corticosteroid use during the course of glioblastoma. Details of how selected pathophysiological aspects of brain edema occurring during the course of glioblastoma and its treatment intersect with the established action of the three old drugs of SEC indicate that they can be repurposed to reduce that edema. Current first-line treatment of this edema is dexamethasone or related corticosteroids. There are multiple negative prognostic implications of both the edema itself and of dexamethasone, prime among them shortened survival, making a dexamethasone sparing regimen highly desirable. SEC uses spironolactone, an antihypertensive potassium-sparing diuretic acting by mineralocorticoid receptor inhibition, ecallantide acting to inhibit kallikrein activation marketed to treat hereditary angioedema, and clotrimazole, an old antifungal drug that inhibits intermediate conductance Ca++ activated K+ channel (KCa3.1). These three old drugs are well known to most clinicians, have a well-tolerated safety history, and have a robust preclinical database showing their potential to reduce the specific edema of glioblastoma. Additionally, these three drugs were chosen by virtue of each having preclinical evidence of glioblastoma growth and/or migration inhibition independent of their edema reduction action. A clinical study of SEC is being planned.
Asunto(s)
Clotrimazol , Glioblastoma , Clotrimazol/uso terapéutico , Dexametasona , Glioblastoma/tratamiento farmacológico , Humanos , Péptidos , Proyectos Piloto , Espironolactona/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: Since the introduction of recombinant tissue plasminogen activator (rtPA) into clinical practice in the mid 1990s, no adjunctive treatment has further improved clinical outcomes in patients with ischemic stroke. The safety, feasibility, and efficacy of combining intravenous (IV) rtPA with endovascular interventions has been described; however, no direct comparative study has yet established whether endovascular interventions after IV rtPA are superior to IV rtPA alone. A retrospective case-control study was designed to address this issue. MATERIALS AND METHODS: Between 2003 and 2006, 33 consecutive patients with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) scores >/=10 were treated with IV rtPA in combination with endovascular interventions (IV plus intervention) at a tertiary care facility. Outcomes were compared with a control cohort of 30 consecutive patients treated with IV rtPA (IV only) at a comparable facility where endovascular interventions were not available. RESULTS: Baseline parameters were similar between the 2 groups. We found that the IV-plus-intervention group experienced significantly lower mortality at 90 days (12.1% versus 40.0%, P = .019) with a significantly greater improvement in NIHSS scores by the time of discharge or follow-up (P = .025). In the IV-plus-intervention group, patients with admission NIHSS scores between 10 and 15 and patients /=10, there was a suggestion of incremental clinical benefit among patients receiving endovascular interventions following standard administration of IV rtPA.
Asunto(s)
Isquemia Encefálica/mortalidad , Isquemia Encefálica/terapia , Embolización Terapéutica/estadística & datos numéricos , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapia , Terapia Trombolítica/estadística & datos numéricos , Activador de Tejido Plasminógeno/administración & dosificación , Enfermedad Aguda , Anciano , Estudios de Casos y Controles , Terapia Combinada/mortalidad , Terapia Combinada/estadística & datos numéricos , Embolización Terapéutica/mortalidad , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Minnesota/epidemiología , Proteínas Recombinantes/administración & dosificación , Recuperación de la Función , Análisis de Supervivencia , Tasa de Supervivencia , Terapia Trombolítica/mortalidad , Activador de Tejido Plasminógeno/genética , Resultado del TratamientoRESUMEN
The p53 gene family, comprising p53, p63, and p73, has overlapping and distinctive functional roles. These members share structural similarities allowing for dynamic interplay in the activation of genes that are important in development and key cellular functions, such as the induction of apoptosis. Whereas p53 is a classical tumor suppressor gene, p63 and p73 do not share this feature in cancer formation and progression. The compensation in the expression level of these members in a background that is deficient for one of them has not been examined previously. Given the importance of p63 in the development and differentiation of oral-esophageal stratified squamous epithelia and the absence of oral-esophageal tumors in p53-null mice, we postulated and describe herein that p63 expression is associated with the loss of p53 in a p53-deficient background. Both full-length and amino-truncated forms of p63 are expressed and increased in oral-esophageal epithelia of p53-null mice when compared with wild-type mice, and the induction of p21 may potentially be preserved through the increase of p63.
Asunto(s)
Esófago/metabolismo , Proteínas de la Membrana , Mucosa Bucal/metabolismo , Fosfoproteínas/biosíntesis , Transactivadores/biosíntesis , Proteína p53 Supresora de Tumor/deficiencia , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Proteínas de Unión al ADN , Epitelio/metabolismo , Epitelio/fisiología , Esófago/citología , Esófago/fisiología , Genes Supresores de Tumor , Genes p53/fisiología , Humanos , Inmunohistoquímica , Ratones , Mucosa Bucal/citología , Mucosa Bucal/fisiología , Fosfoproteínas/genética , Transactivadores/genética , Factores de Transcripción , Transfección , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de TumorRESUMEN
Women's College Hospital (WCH), Toronto, Canada, embarked on a review of 5 years of Web-based e-mail communications to address broad issues of managerial policy and procedure as related to the institution's expanding role in Web-based communication. The hospital looked at who was sending messages, why they were communicating, and how the institution should respond to the new demands placed on them by virtual communicators. The article provides a brief discussion of the results of the review and points out that attention must be given to a broad range of organizational challenges and opportunities posed by such communications. Suggestions related to how health care organizations may respond better to and serve their virtual audiences are offered.
Asunto(s)
Redes de Comunicación de Computadores/estadística & datos numéricos , Sistemas de Información en Hospital/estadística & datos numéricos , Hospitales Generales/organización & administración , Internet/estadística & datos numéricos , Redes de Comunicación de Computadores/organización & administración , Recolección de Datos , Sistemas de Comunicación en Hospital , Departamentos de Hospitales/estadística & datos numéricos , Humanos , Internet/organización & administración , Ontario , Consulta Remota , Telecomunicaciones/tendencias , Revisión de Utilización de RecursosRESUMEN
Spinal cord ischemia with resultant paraplegia or paraparesis remains an important clinical problem after operations on the thoracoabdominal aorta. Because hypothermia has a protective effect on ischemic neural tissue, we developed a baboon model of spinal cord ischemia to simulate the situation encountered clinically for resection of aneurysms of the thoracoabdominal aorta and to determine whether profound hypothermia produced by hypothermic cardiopulmonary bypass has a protective effect on spinal cord function. After cardiopulmonary bypass was established, the aorta was clamped distal to the left subclavian artery and proximal to the renal arteries for 60 minutes. Group I animals (n = 9) underwent aortic clamping at normothermia (37 degrees C), and group II animals (n = 9) were cooled to a rectal temperature of 15 degrees C before aortic clamping and underwent cardiopulmonary bypass at this temperature until the aorta was unclamped. Of the eight operative survivors in group I, six animals were paraplegic and two were paraparetic, whereas all six group II animals that survived the procedure were neurologically intact (p = 0.0002). The protective effect of hypothermia was associated with blunting of the hyperemic response of spinal cord blood flow (determined by the radioactive microsphere technique) in the lower thoracic and the lumbar segments of the spinal cord after unclamping of the aorta. Profound hypothermia produced by hypothermic cardiopulmonary bypass may be an effective method of protection of the spinal cord in patients undergoing repair of aneurysms of the thoracoabdominal aorta and may reduce the prevalence of ischemic injury to the spinal cord.