RESUMEN
To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression.
Asunto(s)
Susceptibilidad a Enfermedades/inmunología , Gammopatía Monoclonal de Relevancia Indeterminada/inmunología , Mieloma Múltiple/inmunología , Neutrófilos/inmunología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/inmunología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/tratamiento farmacológico , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/mortalidad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Neutrófilos/metabolismo , Fagocitosis/genética , Fagocitosis/inmunología , Transducción de Señal/genética , Escape del Tumor/genéticaRESUMEN
A patient with Turner's syndrome developed childhood depression at age 11 and exhibited symptoms of anorexia nervosa at age 17. Although this patient's eating habits normalized with treatment, the depressive symptoms persisted at 1-year follow-up. The possibility that anorexia nervosa may be secondary to a mood disorder in patients with Turner's syndrome is discussed.
Asunto(s)
Anorexia Nerviosa/complicaciones , Trastorno Depresivo/complicaciones , Síndrome de Turner/complicaciones , Adolescente , Anorexia Nerviosa/etiología , Niño , Femenino , Estudios de Seguimiento , HumanosRESUMEN
The inpatient aspect of a comprehensive treatment program is detailed, including the daily hospital routine and description of professional staff personnel. The author provides an overview of the educational materials available to patients and their families to promote increased awareness of all facets of eating disorders. Categories of treatment for the care of anorectics and bulimics are detailed, and the importance of support systems in the form of self-help groups for patients and their families is stressed throughout.