Spontaneous cerebral calcific embolus from the aortic arch.

Spontaneous calcific embolism is an uncommon cause of stroke. In most cases calcified cardiac valves are the sources of the emboli although embolization of calcific material from the brachiocephalic trunk has also been described. We report a case of stroke attributable to spontaneous calcific emboli from the aortic arch in which migration of the emboli was observed along the middle cerebral artery following iv tPA.

Selective targeting of death receptor 5 circumvents resistance of MG-63 osteosarcoma cells to TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a tumor necrosis factor superfamily member, targets death receptors and selectively kills malignant cells while leaving normal cells unaffected. However, unlike most cancers, many osteosarcomas are resistant to TRAIL. To investigate this resistance, we characterized the response of MG-63 osteosarcoma cells and hPOB-tert osteoblast-like cells to TRAIL and agonist antibodies to death receptor 4 (DR4) and death receptor 5 (DR5). We found that MG-63 osteosarcoma cells and hPOB-tert osteoblast-like cells show no or very little response to TRAIL or a DR4 agonist, but MG-63 cells undergo apoptosis in response to a DR5 agonist. Analysis of TRAIL receptor expression showed that normal osteoblastic and osteosarcoma cells express a variety of TRAIL receptors but this does not correlate to TRAIL responsiveness. Production of the soluble decoy receptor osteoprotegerin also could not explain TRAIL resistance. We show that TRAIL activates the canonical caspase-dependent pathway, whereas treatment with cycloheximide increases the sensitivity of MG-63 cells to TRAIL and anti-DR5 and can also sensitize hPOB-tert cells to both agents. Proapoptotic and antiapoptotic protein expression does not significantly differ between MG-63 and hPOB-tert cells or change following treatment with TRAIL or anti-DR5. However, sequencing the death domain of DR4 in several osteoblast-like cells showed that MG-63 osteosarcoma cells are heterozygous for a dominant-negative mutation, which can confer TRAIL resistance. These results suggest that although the dominant-negative form of the receptor may block TRAIL-induced death, an agonist antibody to the active death receptor can override cellular defenses and thus provide a tailored approach to treat resistant osteosarcomas.

Bone biology and the pathogenesis of osteoporosis.

Much is now known about skeletal biology and the changes that take place during diseases. Skeletal development is programmed by the sequential activation of specific genetic pathways that culminate in the production of the adult skeleton, which is light but strong. Systemic hormones including parathyroid hormone, vitamin D metabolites, and calcitonin regulate blood calcium levels and contribute to the overall calcium economy of the body. Many other hormones have subtle but important effects on skeletal behaviour and its modelling and remodelling activity. At a local level, the integration of cellular differentiation and function within the microenvironment of bone is under the influence of a large number of cytokines and growth factors. Osteoporosis is a very common disorder and is a result of perturbation in these regulatory mechanisms. Much has been learnt in recent years about the many pathogenic processes that contribute to bone loss and fragility. Several drug treatments are now available to prevent bone loss and reduce the incidence of fractures, and there are prospects for the development of further novel pharmacological interventions that may modify some of the pathogenic processes themselves. Among the newer pathways for pharmacological intervention, the calcium-sensing receptor and the receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin system involved in osteoblast-osteoclast interactions offer exciting opportunities.

Absceso de psoas. Descripción de una serie de 23 casos / Abscess of the psoas muscle. Description of a serie of 23 cases

FUNDAMENTOS. El absceso del músculo psoas (AP) es una entidad clínica infrecuente y de difícil diagnóstico. Durante la última década, el número de casos diagnosticados ha aumentado como consecuencia del uso generalizado de técnicas de imagen: ecografía y tomografía computadorizada. MÉTODOS. Se han estudiado retrospectivamente 23 casos diagnosticados de AP durante el período 1992-2000 en un hospital de tercer nivel. RESULTADOS. Dieciséis de los 23 abscesos fueron clasificados como secundarios: las entidades nosológicas más frecuentes fueron espondilodiscitis y pielonefritis. El dolor abdominal y a la movilización de la cadera homolateral fueron las manifestaciones clínicas más usuales. La duración de los síntomas antes del diagnóstico superó los 7 días. Staphylococcus aureus fue el microorganismo aislado con mayor frecuencia seguido de Eschericia coli y Mycobacterium tuberculosis. Todos los AP fueron diagnosticados mediante tomografía computadorizada. En 7 pacientes se realizó drenaje percutáneo, mientras que en 9 se efectuó drenaje quirúrgico. Cuatro pacientes con AP murieron y en sólo 3 casos hubo recurrencias. CONCLUSIONES. Una clínica inespecífica y una presentación subaguda dificultan el diagnóstico de AP. La antibioterapia de amplio espectro unido al drenaje (percutáneo o quirúrgico) debe considerarse el tratamiento de elección (AU)