RESUMO
The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Pretreatment strategies to prevent sepsis have received inadequate consideration, especially in the premature neonate, where outcomes from sepsis are so dismal. Aluminium salts-based adjuvants (alum) are used currently in many paediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pretreatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis. Subcutaneous alum pretreatment improves survival to polymicrobial sepsis in both wild-type and T and B cell-deficient neonatal mice, but not in caspase-1/11 null mice. Moreover, alum increases peritoneal macrophage and neutrophil phagocytosis, and decreases bacterial colonization in the peritoneum. Bone marrow-derived neutrophils from alum-pretreated neonates produce more neutrophil extracellular traps (NETs) and exhibit increased expression of neutrophil elastase (NE) after in-vitro stimulation with phorbol esters. In addition, alum pretreatment increases bone marrow and splenic haematopoietic stem cell expansion following sepsis. Pretreatment of neonatal mice with an alum-based adjuvant can stimulate multiple innate immune cell functions and improve survival. These novel findings suggest a therapeutic pathway for the use of existing alum-based adjuvants for preventing sepsis in premature infants.
Assuntos
Adjuvantes Imunológicos , Compostos de Alúmen/uso terapêutico , Vacinas Bacterianas/imunologia , Macrófagos Peritoneais/imunologia , Células Mieloides/fisiologia , Neutrófilos/imunologia , Sepse/imunologia , Animais , Animais Recém-Nascidos , Linfócitos B/fisiologia , Caspase 1/genética , Caspase 1/metabolismo , Caspases/genética , Caspases/metabolismo , Caspases Iniciadoras , Autorrenovação Celular , Modelos Animais de Doenças , Armadilhas Extracelulares/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fagocitose , Sepse/prevenção & controle , Linfócitos T/fisiologiaRESUMO
Thromboelastography (TEG) is a viscoelastic test that allows rapid evaluation of clot formation and fibrinolysis from a sample of whole blood. TEG is increasingly utilized to guide blood product resuscitation in surgical patients and transfusions for liver transplant patients. Patients with severe liver failure have significant derangement of their clotting function due to impaired production of procoagulant and anticoagulant factors. Traditional coagulation studies are limited by the short time needed for the result and provide little information about the dynamics and strength of clot formation. In addition, traditional coagulation studies do not correlate well with bleeding episodes and may lead to over-transfusion of various blood products. Evidence is less robust regarding the use of TEG for transfusion management decisions in severe liver failure patients awaiting, undergoing, or immediately after liver transplant surgery. However, the available evidence suggests that systematic implementation of TEG rather than traditional coagulation studies results in the administration of fewer blood products without increased mortality or complications. The purpose of this study is to review the literature regarding the use of TEG in liver failure patients prior to liver transplant, intraoperatively, and postoperatively. Additional high-quality randomized controlled studies should be performed to evaluate the use of TEG to guide transfusion decisions, particularly in the postoperative period following liver transplantation.
Assuntos
Transplante de Fígado/métodos , Tromboelastografia/métodos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The effects of patient movement and position on the drip-rate accuracy of several i.v. flow-regulating devices were investigated. Intravenous infusion sites were established in 20 healthy adult volunteers. All the subjects received 5% dextrose injection through the same type of i.v. tubing from 500-mL bags hung from standard i.v. fluid poles. The flow-regulating devices tested were the IVAC 280, which served as the control device; a roller clamp; the Dial-A-Flo; the Exacdrop; and the 3M IV Flow Regulator. Drip rates were present at 40 drops/min and were measured before and after the subjects moved among the supine, sitting, and standing positions and walking. The drip rate was reset to 40 drops/min after each position change. Changing position from supine to sitting did not affect mean drip rates for the IVAC 280 and 3M IV Flow Regulator devices but significantly decreased the rates for the roller clamp, Dial-A-Flo, and Exacdrop. The change from sitting to standing did not affect the IVAC 280 and 3M IV Flow Regulator drip rates but significantly decreased the rates for the other devices. None of the rates was dramatically affected when the subjects went from standing to walking, although the effect achieved significance for the roller clamp and Exacdrop devices. The change from walking to the supine position did not affect the drip rates for the IVAC 280 and 3M IV Flow Regulator but significantly increased the rates for the other devices. The drip-rate accuracy of the roller clamp, Dial-A-Flo, and Exacdrop devices was significantly affected when subjects changed positions.(ABSTRACT TRUNCATED AT 250 WORDS)