RESUMEN
Spinal anesthesia is widely regarded as a reasonable anesthetic option for cesarean delivery in severe preeclampsia, provided there is no indwelling epidural catheter or contraindication to neuraxial anesthesia. Compared with healthy parturients, those with severe preeclampsia experience less frequent, less severe spinal-induced hypotension. In severe preeclampsia, spinal anesthesia may cause a higher incidence of hypotension than epidural anesthesia; however, this hypotension is typically easily treated and short lived and has not been linked to clinically significant differences in outcomes. In this review, we describe the advantages and limitations of spinal anesthesia in the setting of severe preeclampsia and the evidence guiding intraoperative hemodynamic management.
Asunto(s)
Anestesia Obstétrica , Anestesia Raquidea , Cesárea/métodos , Preeclampsia/terapia , Adulto , Anestesia Epidural , Anestesia General , Trastornos de la Coagulación Sanguínea/complicaciones , Femenino , Hemodinámica/fisiología , Humanos , Hipotensión/inducido químicamente , Hipotensión/etiología , Monitoreo Intraoperatorio , EmbarazoRESUMEN
The disease state of cancer appears late in tumor development. Before being diagnosed, a tumor can remain for prolonged periods of time in a dormant state. Dormant human cancer is commonly defined as a microscopic tumor that does not expand in size and remains asymptomatic. Dormant tumors represent an early stage in tumor development and may therefore be a potential target for nontoxic, antiangiogenic therapy that could prevent tumor recurrence. Here, we characterize an experimental model that recapitulates the clinical dormancy of human tumors in mice. We demonstrate that these microscopic dormant cancers switch to the angiogenic phenotype at a predictable time. We further show that while angiogenic liposarcomas expand rapidly after inoculation of tumor cells in mice, nonangiogenic dormant liposarcomas remain microscopic up to one-third of the normal severe combined immune deficiency (SCID) mouse life span, although they contain proliferating tumor cells. Nonangiogenic dormant tumors follow a similar growth pattern in subcutaneous (s.c.) and orthotopic environments. Throughout the dormancy period, development of intratumoral vessels is impaired. In nonangogenic dormant tumors, small clusters of endothelial cells without lumens are observed early after tumor cell inoculation, but the nonangiogenic tumor cannot sustain these vessels, and they disappear within weeks. There is a concomitant decrease in microvessel density, and the nonangiogenic dormant tumor remains harmless to the host. In contrast, microvessel density in tumors increases rapidly after the angiogenic switch and correlates with rapid expansion of tumor mass. Both tumor types cultured in vitro contain fully transformed cells, but only cells from the nonangiogenic human liposarcoma secrete relatively high levels of the angiogenesis inhibitors thrombospondin-1 and TIMP-1. This model suggests that as improved blood or urine molecular biomarkers are developed, the microscopic, nonangiogenic, dormant phase of human cancer may be vulnerable to antiangiogenic therapy years before symptoms, or before anatomical location of a tumor can be detected, by conventional methods.
Asunto(s)
Liposarcoma/irrigación sanguínea , Liposarcoma/patología , Neovascularización Patológica/fisiopatología , Animales , Línea Celular Tumoral , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Liposarcoma/metabolismo , Masculino , Ratones , Ratones SCID , Neovascularización Patológica/patología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The NPC is the portal for the exchange of proteins, mRNA, and ions between nucleus and cytoplasm. Many small molecules (<10 kDa) permeate the nucleus by simple diffusion through the pore, but molecules larger than 70 kDa require ATP and a nuclear localization sequence for their transport. In isolated Xenopus oocyte nuclei, diffusion of intermediate-sized molecules appears to be regulated by the NPC, dependent upon [Ca(2+)] in the nuclear envelope. We have applied real-time imaging and fluorescence recovery after photobleaching to examine the nuclear pore permeability of 27-kDa EGFP in single intact cells. We found that EGFP diffused bidirectionally via the NPC across the nuclear envelope. Although diffusion is slowed approximately 100-fold at the nuclear envelope boundary compared to diffusion within the nucleus or cytoplasm, this delay is expected for the reduced cross-sectional area of the NPCs. We found no evidence for significant nuclear pore gating or block of EGFP diffusion by depletion of perinuclear Ca(2+) stores, as assayed by a nuclear cisterna-targeted Ca(2+) indicator. We also found that EGFP exchange was not altered significantly during the cell cycle.