RESUMEN
Abatacept is the first in a new class of agents that selectively modulates T-cell activation by attenuating CD28-mediated co-stimulation. This study examined the effects of abatacept on disease development in a rat model of collagen-induced arthritis (CIA). The rats were treated with either abatacept (1mg/kg) or control IgG beginning at the time of induction of CIA. By day 16, significant paw swelling was observed in IgG-treated control animals that continued to increase, reaching a plateau on day 21. Prophylactic treatment with abatacept completely abrogated paw swelling throughout the study. Histopathology demonstrated a significant reduction in inflammation, cartilage destruction, bone resorption and pannus formation. Abatacept treatment resulted in 90% inhibition of circulating collagen-specific antibodies and decreased the serum expression of many cytokines and chemokines that were upregulated in diseased animals. Immunohistochemical analysis of the ankle joints demonstrated that interleukin-6 production was reduced in the tissues and the numbers of osteoclasts present in the joints were also decreased. Ankle microcomputer tomography (micro-CT) analyses dramatically demonstrated the protective effects of abatacept on bone destruction in these animals. Data presented here demonstrate that prophylactic administration of abatacept significantly inhibits the onset and progression of disease in a rat CIA model, with reductions in inflammation, inflammatory mediators, and bone and joint destruction.
Asunto(s)
Artritis Experimental/prevención & control , Resorción Ósea/prevención & control , Colágeno/inmunología , Inmunoconjugados/farmacología , Abatacept , Fosfatasa Ácida/metabolismo , Animales , Artritis Experimental/inmunología , Autoanticuerpos/biosíntesis , Resorción Ósea/inmunología , Huesos/efectos de los fármacos , Huesos/inmunología , Huesos/patología , Modelos Animales de Enfermedad , Femenino , Inflamación/inducido químicamente , Inflamación/prevención & control , Isoenzimas/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/enzimología , Ratas , Articulaciones Tarsianas/efectos de los fármacos , Articulaciones Tarsianas/inmunología , Fosfatasa Ácida TartratorresistenteRESUMEN
A retrospective survey of mothers' attitudes toward and experiences of chorionic villus sampling, amniocentesis and dexamethasone (DEX) treatment was conducted in 38 women who underwent a prenatal diagnostic procedure for congenital adrenal hyperplasia because of a previously affected child (n = 37) or because the mother herself was affected (n = 1). Both diagnostic procedures were well tolerated and almost every woman said that the anxiety or discomfort associated with the procedure was far outweighed by the value of knowing whether or not her fetus was affected. The earlier diagnostic information provided by chorionic villus sampling was highly valued. Maternal side-effects of DEX were common (75%) and more than one-third of the women rated one or more side-effects as "severe' (weight gain, fatigue, stomach pain, irritability, facial hair growth). Many women expressed anxiety about possible short- and long-term side-effects of DEX on their unborn children and themselves but all said they would undergo DEX treatment again to prevent virilization.
Asunto(s)
Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Actitud Frente a la Salud , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Madres/psicología , Diagnóstico Prenatal/psicología , Adulto , Amniocentesis/psicología , Ansiedad/psicología , Muestra de la Vellosidad Coriónica/psicología , Femenino , Humanos , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
The effect of early prenatal dexamethasone (DEX) exposure on cognitive and behavioral development, behavior problems, and temperament were examined in 26 consecutively identified children aged 6 mo to 5 1/2 years, whose mothers had been DEX-treated during pregnancy because their offspring was at risk for congenital adrenal hyperplasia (CAH), and compared with 14 children from untreated CAH-risk pregnancies. Three children in each group were CAH-affected. Assessments were performed by way of mother-completed standard questionnaires. No significant differences in cognitive abilities or behavior problems were identified. On temperament questionnaires, DEX-exposed children showed more Shyness (p < .004), greater Emotionality (p < .03), less Sociability (p < .04), and a trend for greater Avoiddance (p < .07) than unexposed children. DEX-exposed children also had significantly higher Internalizing (p < .002) and Total Problem scores (p < .05) on the behavior problem measure for 2-3 year olds. The results should be considered preliminary until they have been replicated by the study of a larger sample and direct examination of the children.
Asunto(s)
Conducta Infantil/efectos de los fármacos , Desarrollo Infantil/efectos de los fármacos , Cognición/efectos de los fármacos , Dexametasona/farmacología , Efectos Tardíos de la Exposición Prenatal , Hiperplasia Suprarrenal Congénita/epidemiología , Hiperplasia Suprarrenal Congénita/fisiopatología , Niño , Conducta Infantil/fisiología , Desarrollo Infantil/fisiología , Preescolar , Cognición/fisiología , Dexametasona/efectos adversos , Femenino , Humanos , Lactante , Intercambio Materno-Fetal , Proyectos Piloto , Embarazo , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Administration of the Revised Diagnostic Interview for Borderlines to 14 adolescent girls showed that the 10 who had chart diagnoses of Borderline Personality Disorder or such features earned significantly higher scores than the 4 nonborderline adolescents. The small sample warrants replication but results suggest the interview seems appropriate in research with adolescent girls.
Asunto(s)
Trastorno de Personalidad Limítrofe/diagnóstico , Hospitalización , Determinación de la Personalidad/estadística & datos numéricos , Adolescente , Trastorno de Personalidad Limítrofe/clasificación , Trastorno de Personalidad Limítrofe/psicología , Femenino , Humanos , Entrevista Psicológica , Psicometría , Reproducibilidad de los ResultadosRESUMEN
The case of an adolescent hospitalized on an Acute Inpatient Unit following a suicide attempt is presented. Aspects of the patient's clinical presentation, specifically highly variable behaviors that eventuated in three recurring personality constellations, are linked to the youth's history of physical abuse. Interpretations of the boy's behaviors and treatment strategies are illustrated for consideration in work with other youth suffering histories of abuse.