Improved Outcomes With Integrated Intensivist Consultation for Cardiac Surgery Patients.

This study examined the impact of integrated intensivist consultation in the immediate postoperative period on outcomes for cardiac surgery patients. A retrospective cohort study was conducted in 1711 adult cardiac surgery patients from a single quaternary care center in Minnesota. Outcomes were compared across 2 consecutive 2-year time periods reflecting an elective intensivist model (n = 801) and an integrated intensivist model (n = 910).

Percutaneous Venoarterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock Is Associated with Improved Short- and Long-Term Survival.

Mortality due to refractory cardiogenic shock (RCS) exceeds 50%. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become an accepted therapy for RCS. The aim of our study was to evaluate outcomes of patients with RCS treated with percutaneous VA-ECMO (pVA-ECMO).

Development and pilot testing of an OSCE for difficult conversations in surgical intensive care.

Objectives: To describe the development and results of an Objective Structured Clinical Exam (OSCE) for leading family conferences in the surgical intensive care unit (SICU).

Design: Pilot demonstration and reliability assessment.

Setting: General surgery residency program at a major academic teaching hospital.

A novel MyD-1 (SIRP-1alpha) signaling pathway that inhibits LPS-induced TNFalpha production by monocytes.

MyD-1 (CD172) is a member of the family of signal regulatory phosphatase (SIRP) binding proteins, which is expressed on human CD14+ monocytes and dendritic cells. We now show a novel role for MyD-1 in the regulation of the innate immune system by pathogen products such as lipopolysaccharide (LPS), purified protein derivative (PPD), and Zymosan. Specifically, we demonstrate that ligation of MyD-1 on peripheral blood mononuclear cells (PBMCs) inhibits tumor necrosis factor alpha (TNFalpha) secretion but has no effect on other cytokines induced in response to each of these products.

B cell receptor-stimulated mitochondrial phospholipase A2 activation and resultant disruption of mitochondrial membrane potential correlate with the induction of apoptosis in WEHI-231 B cells.

Cross-linking of the Ag receptors on the immature B cell lymphoma, WEHI-231, leads to growth arrest and apoptosis. We now show that although commitment to such B cell receptor (BCR)-mediated apoptosis correlates with mitochondrial phospholipase A(2) activation, disruption of mitochondrial function, and ATP depletion, it is executed independently of caspase activation. First, we demonstrate a pivotal role for mitochondrial function in determining B cell fate by showing up-regulation of cytosolic phospholipase A(2) expression, induction of mitochondrial phospholipase A(2) activity, arachidonic acid-mediated collapse of mitochondrial transmembrane inner potential (Delta psi(m)), and depletion of cellular ATP under conditions of apoptotic, but not proliferative, signaling via the BCR.

Risk factors and patterns of injury in snowmobile crashes.

Objective: To evaluate risk factors for snowmobile injury and patterns of injury.

Methods: We performed a retrospective analysis of patients with snowmobile injury at three trauma centers. Data were collected from trauma databases and patients charts from January 1988 through April 1996; we obtained statistics from the Minnesota Department of Natural Resources for comparison purposes.

Antagonistic roles for phospholipase D activities in B cell signaling: while the antigen receptors transduce mitogenic signals via a novel phospholipase D activity, phosphatidylcholine-phospholipase D mediates antiproliferative signals.

Cross-linking of the Ag receptors on B cells induces DNA synthesis and proliferation. Butanol trap experiments suggest that one or more phospholipase D activities play a key role in this process. Although phosphatidylcholine-phospholipase D has been shown to play a central role in the transduction of proliferative responses for a wide variety of calcium-mobilizing receptors, we show that the Ag receptors are not coupled to this phospholipase.

A phosphorylcholine-containing filarial nematode-secreted product disrupts B lymphocyte activation by targeting key proliferative signaling pathways.

Filarial nematodes infect more than 100 million people in the tropics, causing elephantiasis, chronic skin lesions, and blindness. The parasites are long-lived as a consequence of being able to evade the host immune system, but an understanding of the molecular mechanisms underlying this evasion remains elusive. In this study, we demonstrate that ES-62 (2 microg/ml), a phosphorylcholine (PC)-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, is able to polyclonally activate certain protein tyrosine kinase and mitogen-activating protein kinase signal-transduction elements in B lymphocytes.

In vivo endotoxin tolerance: impaired LPS-stimulated TNF release of monocytes from patients with sepsis, but not SIRS.

In vitro pretreatment of human monocytes (MO) with low-dose lipopolysaccharide (LPSp) inhibits TNF release in response to subsequent LPSa activation. Septic patients are often indistinguishable from patients with systemic inflammatory response syndrome (SIRS). We hypothesized that in vivo exposure to "septic" stimuli impairs subsequent LPSa-stimulated MO TNF production in vitro.

LPS pretreatment reprograms macrophage LPS-stimulated TNF and IL-1 release without protein tyrosine kinase activation.

Pretreatment of macrophages with low-dose endotoxin (LPSp) profoundly alters cytokine release in response to subsequent LPSa activation. These qualitative and quantitative alterations in cytokine release have been termed macrophage reprogramming. Macrophage activation by LPS is thought to occur via a mechanism involving an early protein tyrosine kinase (PTK) phosphorylation step.

Mechanisms of reprogrammed macrophage endotoxin signal transduction after lipopolysaccharide pretreatment.

Background: Dysregulation of macrophage tumor necrosis factor (TNF) and interleukin-(IL-1) release results from repetitive lipopolysacharride (LPS) stimulation. In this study we investigated the mechanisms of LPS pretreatment (LPSp) signal transduction producing altered LPS-activated (LPSa) cytokine release.

Methods: Murine macrophages were treated with medium alone, actinomycin D, cycloheximide, a protein kinase C inhibitor (H7), or the nitric oxide synthase inhibitor L-NMA.

Independent signal transduction pathways for IL-1 and TNF in LPS-tolerant macrophages.

Macrophages rendered "tolerant" by pretreatment with low-dose endotoxin (LPSp) release less TNF and more IL-1 in response to a second activating endotoxin exposure (LPSa). We hypothesized that LPSp pretreatment alters signal transduction pathways for TNF and IL-1 independently. The effect of pretreatment with LPSp alone was compared to pretreatment with LPSp plus defined second-messenger pathway agonists or antagonists.

Endotoxin pretreatment of human monocytes alters subsequent endotoxin-triggered release of inflammatory mediators.

In trauma or sepsis, monocytes and macrophages release mediators such as tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), and prostaglandin E2 (PGE2). Although patients may be exposed to more than one stimulus, the effect of repetitive endotoxin (LPS) stimulation on human monocytes is poorly characterized. Human peripheral blood monocytes obtained from healthy volunteers were pretreated with endotoxin (LPS1) for 24 h.

Macrophage endotoxin tolerance. Tumor necrosis factor and interleukin-1 regulation by lipopolysaccharide pretreatment.

Objective: To correlate cytokine gene expression with the release of protein product by murine peritoneal macrophages rendered tolerant by sequential endotoxin stimulation in vitro.

Design: In vitro investigation of the regulation of endotoxin-stimulated cytokine production following endotoxin pretreatment using cytokine bioassays, polymerase chain reaction, and Northern blot analyses.

Setting: In vitro cell culture model of sequential endotoxin stimulation of murine macrophages.

Macrophage endotoxin tolerance: effect of TNF or endotoxin pretreatment.

Macrophages pretreated with low-dose endotoxin [lipopolysaccharide (LPS1)] have an altered response to subsequent endotoxin (LPS2) stimulation, a process known as endotoxin tolerance. In this study we investigated whether the LPS1 pretreatment effects were mediated primarily via tumor necrosis factor (TNF alpha). Murine peritoneal macrophages were pretreated in vitro with either TNF alpha or LPS1 and the effects on mediator production in response to a second endotoxin exposure, LPS2, were compared.

Pre-exposure to hypoxia or septic stimuli differentially regulates endotoxin release of tumor necrosis factor, interleukin-6, interleukin-1, prostaglandin E2, nitric oxide, and superoxide by macrophages.

Unlabelled: Shock states with resulting inadequate cellular oxygen delivery may contribute to macrophage (M phi) activation or dysregulation. In this study we compared the effects of transient anoxia and endotoxin pretreatment (LPS1) on M phi mediator release with a second endotoxin stimulus (LPS2).

Methods: In vitro cultures of murine peritoneal exudate M phi were exposed to 2 hours of hypoxic or normoxic conditions, then incubated 22 hours under identical normoxic conditions +/- 10 ng/mL of LPS1 pretreatment.