RESUMO
BACKGROUND: Patients with cancer develop endothelial dysfunction and subsequently display a higher risk of cardiovascular events. The aim of the present work was to examine changes in nitric oxide (NO)- and prostacyclin (PGI2)-dependent endothelial function in the systemic conduit artery (aorta), in relation to the formation of lung metastases and to local and systemic inflammation in a murine orthotopic model of metastatic breast cancer. METHODS: BALB/c female mice were orthotopically inoculated with 4T1 breast cancer cells. Development of lung metastases, lung inflammation, changes in blood count, systemic inflammatory response (e.g. SAA, SAP and IL-6), as well as changes in NO- and PGI2-dependent endothelial function in the aorta, were examined 2, 4, 5 and 6 weeks following cancer cell transplantation. RESULTS: As early as 2 weeks following transplantation of breast cancer cells, in the early metastatic stage, lungs displayed histopathological signs of inflammation, NO production was impaired and nitrosylhemoglobin concentration in plasma was decreased. After 4 to 6 weeks, along with metastatic development, progressive leukocytosis and systemic inflammation (as seen through increased SAA, SAP, haptoglobin and IL-6 plasma concentrations) were observed. Six weeks following cancer cell inoculation, but not earlier, endothelial dysfunction in aorta was detected; this involved a decrease in basal NO production and a decrease in NO-dependent vasodilatation, that was associated with a compensatory increase in cyclooxygenase-2 (COX-2)- derived PGI2 production. CONCLUSIONS: In 4 T1 metastatic breast cancer in mice early pulmonary metastasis was correlated with lung inflammation, with an early decrease in pulmonary as well as systemic NO availability. Late metastasis was associated with robust, cancer-related, systemic inflammation and impairment of NO-dependent endothelial function in the aorta that was associated with compensatory upregulation of the COX-2-derived PGI2 pathway.
Assuntos
Aorta/patologia , Neoplasias da Mama/patologia , Epoprostenol/metabolismo , Neoplasias Pulmonares/patologia , Óxido Nítrico/metabolismo , Animais , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Endotélio Vascular/patologia , Feminino , Inflamação , Pulmão/irrigação sanguínea , Pulmão/patologia , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A 17 year old female guitar player with congenital shortening of the fourth metacarpal in the right hand was successfully treated by distraction lengthening. The fourth metacarpal was lengthened by 22 mm (36%) without complications. The lengthening improved the function and cosmesis of the hand.
Assuntos
Metacarpo/anormalidades , Metacarpo/cirurgia , Osteogênese por Distração/métodos , Adolescente , Feminino , HumanosRESUMO
Experiences are presented with the surgical treatment of 33 patients with traumatic radial nerve injuries after humerus fracture. Diagnostic and surgical difficulties of primary orthopaedic humerus fragment union by osteosynthesis with simultaneous evaluation of the damaged nerve. In the group of patients who had been given primary orthopaedic treatment the causes were analysed of reinnervation failure. In another group of patients undergoing metal plate removal after full bone union had been achieved the own experiences are presented related to an improved method of operative approach and delayed reconstruction of the damaged nerve. The authors suggest reconstruction of radial nerve injury after humerus fracture by specialized teams of orthopaedic surgeons and neurosurgeons.