Background: Traumatic coagulopathy contributes to early death by exsanguination and late in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding improve trauma outcomes. Methods: We performed phase 3 randomized clinical trial evaluating efficacy safety of rFVIIa as an adjunct direct hemostasis major trauma. studied 573 patients (481 blunt 92 penetrating) who bled 4 8 red blood cell (RBC) units within 12 hours injury were still...

Bacterial DNA (bDNA) can activate an innate-immune stimulatory "danger" response via toll-like receptor 9 (TLR9). Mitochondrial (mtDNA) is unique among endogenous molecules in that mitochondria evolved from prokaryotic ancestors. Thus, mtDNA retains molecular motifs similar to bDNA. It unknown, however, whether released by shock or capable of eliciting immune responses like We hypothesized shock-injured tissues might release and act as a danger-associated pattern (or "alarmin") neutrophils...

We examined the role of cytokines in cutaneous response to application trinitrochlorobenzene (TNCB) both nonsensitized and sensitized mice, i.e., irritant reaction (IR) contact hypersensitivity reactions (CH). When administered immediately before challenge, anti-tumor necrosis factor (TNF) antibody abrogated ear swelling CH; directed against interferon gamma or antibodies granulocyte/macrophage colony-stimulating interleukin 3 (IL-3) had a partial inhibitory effect; anti-IL-2 receptor no...

The cutaneous lymphocyte-associated antigen (CLA) is the major T cell ligand for vascular adhesion molecule E-selectin, and it has been proposed to be involved in selective targeting of memory cells reactive with skin-associated Ag inflammatory sites. To further investigate relation CLA responses, we analyzed phenotype circulating patients allergic contact dermatitis atopic (AD) alone vs manifesting bronchopulmonary atopy (asthma or without AD) nonallergic individuals. Significant...

We investigated the presence of interleukin 1 (IL 1)-like molecules in normal unstimulated human epidermal tissue. Epidermis from 21 healthy individuals that was prepared by two different methods showed prostaglandin E2 (PGE2) and collagenase stimulating activity for dermal fibroblasts. All extracts tested were positive thymocyte comitogenic (lymphocyte activating factor; LAF). Removal horny layer decreased IL 1-like activity. In contrast to tissue, freshly isolated peripheral blood...

Trauma and sepsis can cause acute lung injury (ALI) Acute Respiratory Distress Syndrome (ARDS) in part by triggering neutrophil (PMN)-mediated increases endothelial cell (EC) permeability. We had shown that mitochondrial (mt) damage-associated molecular patterns (DAMPs) appear the blood after or shock activate human PMN. So we now hypothesized DAMPs (MTD) like DNA (mtDNA) peptides might play a role increased EC permeability during systemic inflammation proceeded to evaluate underlying...

Objective Concern for thoracolumbar spine (TLS) injuries after major trauma mandates immobilization pending radiographic evaluation. Current protocols use standard posteroanterior and lateral radiographs of the (XR/TLS), but many patients also undergo abdominal or thoracic computed tomographic (CT) scanning. We sought to evaluate whether helical truncal CT scanning performed visceral images as well dedicated XR/TLS. Methods prospectively studied 222 consecutive sustaining high-risk requiring...

Neutrophil activation by infectious and inflammatory signals requires ATP release its feedback through purinergic receptors.

Neutrophil extracellular traps (NETs) are critical for anti-bacterial activity of the innate immune system. We have previously shown that mitochondrial damage-associated molecular patterns (mtDAMPs), including DNA (mtDNA), released into circulation after injury. therefore questioned whether mtDNA is involved in trauma-induced NET formation. Treatment human polymorphoneutrophils (PMN) with induced robust formation, though contrast to phorbol myristate acetate (PMA) stimulation, no...

A study was conducted to compare the Staphylococcus aureus skin colonization of 21 patients with atopic dermatitis (AD) and 22 healthy controls. It found that total aerobe count (total CFU/cm2), S. fraction thereof carrier frequency were significantly higher in apparently normal AD than individuals. In addition, compared density 100 1,000 times 3 different kinds lesional (dermatitic, lichenified impetiginized sites). 190 strains isolated from tested for sensitivity 5 topically used...

In order to develop transcutaneous oxygen tension (PtcO2) measurements into a practical method for assessing peripheral vascular disease, the relationships between extremity and chest wall PtcO2 were examined in subjects with without systemic atherosclerotic disease. The ratio of PtcO2, or regional perfusion index (RPI) assessed limb oxygenation more reliably than did direct measurement by obviating effects changes delivery upon local PtcO2. authors find that oximetry can be used during...

Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% trauma are due to bleeding and occur in the first few hours after injury. Of remaining severely injured patients up 25% develop dysregulated immune response multiple organ dysfunction syndrome (MODS). Despite improvements care, morbidity mortality this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even prompt treatment. The underlying...

To investigate whether CD4+ T cells are predetermined to produce a given pattern of lymphokines, we have used culture system that allows the controlled induction either IL-2- or IL-4-producing cells. Single, freshly isolated murine were activated with Con A, rIL-2, and APC; developing clones split then cultured for an additional 14 days rIL-2 alone anti-CD3 stimulation. Subclones expanded in presence produced predominantly IL-2, although subclones derived from same precursor mitogenic...

Hematopoietic failure has been observed in experimental animals following shock and injury. In humans, bone marrow dysfunction the red cell component characterized by a persistent anemia, low reticulocyte counts, need for repeated transfusions despite adequate iron stores. While quantitative defect white blood count not noted, an alteration function manifesting as increased susceptibility to infection is well established. Since etiology of this anemia remains unknown rarely studied injury,...

The cutaneous lymphocyte-associated Ag (CLA) is expressed by a subset of circulating memory/effector T cells and the vast majority skin-infiltrating cells. CLA thought to target skin-associated inflammatory skin sites interacting with endothelial cell ligand E-selectin (CD62E). We have examined adhesion molecules involved in migration human CLA+ CLA- lymphocytes through IL-1- TNF-alpha-activated nonactivated HUVEC layers under static (nonflow) conditions. CLA-enriched migrated more actively...

We investigated whether polyclonal murine Th1 and Th2 cells obtained after short term culture in vitro were capable of mediating tissue inflammation vivo. Th pulsed with mAb to the TCR/CD3 complex injected into footpads or ears naive syngeneic recipient mice. induced delayed swelling that peaked at 24 48 h lasted > = 5 days. Th2-induced 6 < h. Similar responses also observed athymic nude Lesions both contained a predominant neutrophilic infiltrate h, mainly mononuclear The inflammatory...

The immune environment of human soft-tissue injury is unstudied. We studied fracture hematomas (FxSTH) in 56 patients with high-energy bony fractures. FxSTH serum and mononuclear cells (MNC) as well patient plasma blood MNC were studied. Twenty healthy controls donated MNC. Soluble tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, 6, 8, 10, 12, interferon-gamma by enzyme linked immunosorbent assay. Cells flow cytometry after cell-membrane stains for CD-14, TNF-alpha (mTNF),...

Background: Bleeding is one of the leading causes preventable death after traumatic injury. Trauma-associated coagulopathy complicates control bleeding. The published approaches on management this differ significantly. Methods: A qualitative international survey clinical practice among senior physicians responsible for treatment patients with multiple injuries (Injury Severity Score ≥16) was conducted to document common practices, highlight variabilities, and profile rationale behind...