Biomedical subjects

Matthew R Rosengart

Publications and source records attributed to Matthew R Rosengart.

7 recordsLinked to original sources

PubMed2006

The Duffy antigen modifies systemic and local tissue chemokine responses following lipopolysaccharide stimulation.

The Duffy blood group Ag (dfy) binds selective CXC and CC chemokines at high affinity and is expressed on erythrocytes and endothelial cells. However, it does not transmit a signal via G proteins, as occurs with other seven-transmembrane receptors. We hypothesized that dfy functions as a chemokine reservoir and regulates inflammation by altering soluble chemokine concentrations in the blood and tissue compartments. We determined whether Duffy Ag "loss-of-function" phenotypes (human and murine) are associated with alterations in plasma chemokine concentrations during the innate inflammatory response to LPS. Plasma CXCL8 and CCL2 concentrations from humans homozygous for the GATA-1 box polymorphism, a dfy polymorphism that abrogates erythrocyte chemokine binding, were higher than in heterozygotes following LPS stimulation of their whole blood in vitro. Similarly, dfy(-/-) mice showed higher plasma MIP-2 concentrations than dfy(+/+) mice following LPS stimulation of whole blood in vitro. We then determined the relative contributions of erythrocyte and endothelial Duffy Ag in modifying chemokine concentrations and neutrophil recruitment in the lungs following intratracheal LPS administration in dfy(-/-) and dfy(+/+) mice reconstituted with dfy(-/-) or dfy(+/+) marrow. Mice lacking endothelial dfy expression had higher MIP-2 and keratinocyte chemoattractant concentrations in the airspaces. Mice lacking erythrocyte dfy had higher MIP-2 and keratinocyte chemoattractant concentrations in the lung tissue vascular space, but lower plasma chemokine concentrations associated with attenuated neutrophil recruitment into the airspaces. These data indicate that dfy alters soluble chemokine concentrations in blood and local tissue compartments and enhances systemic bioavailability of chemokines produced during local tissue inflammation.

Adolescent↗

PubMed2006

Critical care medicine: landmarks and legends.

Critical care medicine was born from the selective pressures of human disease, and with the perseverance and foresight of a select few pioneers, has become an independent field of medicine. This introduction travels back in time to evaluate those visionaries and their landmark contributions. Advancements in caring for the critically ill and organ failure occurred during the wars of the twentieth century. Landmark advances in the management of respiratory paralysis occurred in the polio epidemic of the 1940s. It was during this era that the world's first ICU was developed. Contemporary critical care differs considerably from that which marked its birth. Much of the technology we currently employ is assumed: invasive hemodynamic monitoring, mechanical ventilation, antisepsis, and antibiotics.

Antisepsis↗

PubMed2006

Prospective payments in a regional trauma center: the case for recognition of the transfer patient in diagnostic related groups.

BACKGROUND: Transfer patients (TP) differ from patients transported directly from the field (DP) by virtue of their complexity and delays to definitive care, factors that might impact on costs and resource utilization and aggravate the adverse selection that already threatens TC reimbursement. METHODS: This is a retrospective cohort study where patients admitted to a Level I trauma center were classified as a TP or DP. Crude and adjusted total costs, complications, length of stay, and proportion of DRG outliers were compared across the two cohorts. RESULTS: Among 8,665 patients, 40% were transferred. TP were more likely to be DRG outliers (15% versus 10%, p < 0.001). Costs in 65% of the DRGs were higher in the TP. Rates of complications and length of stay were significantly greater in the TP. CONCLUSION: There are systematic differences in resource consumption between transferred patients and patients transported directly from the field. These differences render conventional DRG-based mechanisms of reimbursement inadequate, suggesting a need for recognition of the transfer patient as a distinct entity by payers.

Adult↗

PubMed2006

Nonoperative management of severe blunt splenic injury: are we getting better?

BACKGROUND: Most minor splenic injuries are readily treated nonoperatively but controversy exists regarding the role of nonoperative management for higher-grade injuries. The infrequency of these injuries has made evaluation of factors critical to their management difficult. METHODS: Through the National Trauma Data Bank, 3,085 adults sustaining severe (Abbreviated Injury Scale score > or = 4) blunt splenic injury from 1997 to 2003 were retrospectively reviewed. Patient management, demographic information, physiologic data, procedures performed, and outcomes were analyzed. RESULTS: Nonoperative management was attempted in 40.5% of patients but ultimately failed in 54.6% of those. Failure of nonoperative management was associated with increased age, low admission systolic blood pressure, higher injury severity score, and increased hospital and intensive care unit length of stay. Mortality associated with failure of nonoperative management (12.3%) and successful observation (13.8%) was similar. CONCLUSIONS: Nonoperative management of higher-grade splenic injuries is associated with a high rate of failure and prolonged hospital stay. Careful judgment must be exercised in applying nonoperative management to patients with severe splenic injuries.

Adult↗

PubMed2003

Mitogen-activated protein kinases in the intensive care unit: prognostic potential.

OBJECTIVE: To evaluate the prognostic significance of the activational status of p38, specifically progression to multiple organ dysfunction syndrome (MODS), in a group of severely injured trauma patients. SUMMARY BACKGROUND DATA: To date, therapeutic manipulation of the host immunoinflammatory response has not affected the outcome of patients with MODS. A major concern is the inability to identify the patient most at risk so as to enable early intervention. METHODS: Nineteen trauma patients underwent bronchoalveolar lavage (BAL). Cells obtained were plated, stimulated with lipopolysaccharide (LPS), and then harvested at varying time points after stimulation. p38 was evaluated by Western blot. RESULTS: Nineteen patients were categorized into two groups according to baseline and LPS-stimulated p38 activation in cells obtained by BAL. Group 1 demonstrated a 10-fold increase in p38 activation with LPS treatment over unstimulated controls. Group 2 had high baseline levels of p38 that were unresponsive to subsequent LPS stimulation. Both groups were similar with respect to age, gender, shock (systolic blood pressure < 90), Injury Severity Score, APACHE II, lactate levels, base deficit, blood transfusions, and the cell differential of BAL fluid. However, patients in group 2 had a greater incidence of progression to MODS as defined by the Marshall MOD score, a longer duration of mechanical ventilation, a longer stay in the intensive care unit, and a longer overall hospital stay than group 1. CONCLUSIONS: These results demonstrate the prognostic significance of p38 activation in predicting outcome in critically ill trauma patients. Furthermore, these results demonstrate that trauma populations identical by current scoring systems contain a mixture of patients with markedly different outcomes as identified by p38 activation. Measurement of p38 may enable early identification of a subgroup of patients at increased risk for MODS to permit effective therapeutic intervention.

APACHE↗

PubMed2002

The actin cytoskeleton: an essential component for enhanced TNFalpha production by adherent monocytes.

Monocyte adherence induces the formation of focal adhesions, the interaction sites of intracellular signaling molecules and cytoskeletal proteins such as actin. We previously demonstrated that adherence potentiates human monocyte LPS-induced TNFalpha production. Hence, we hypothesized that the actin cytoskeleton is integral to adherence-induced priming for enhanced LPS-induced TNFalpha production. In contrast to nonadherent cells, LPS induced significant transcription of TNFalpha mRNA and production of TNFalpha in adherent monocytes. Disrupting the actin cytoskeleton with cytochalasin D (CD) in adherent monocytes inhibited LPS-induced TNFalpha production by 55%, thereby abrogating adherence-induced priming. Moreover, CD pretreatment abrogated adherence-induced activation of Pyk2, a major focal adhesion kinase, and ERK 1/2, a component of the mitogen-activated protein kinase (MAPK) signaling pathway, and it completely inhibited LPS-induced ERK 1/2 activation. However, CD treatment of nonadherent monocytes failed to inhibit cytokine production. In conclusion, the actin cytoskeleton is integral in the reprogramming of the monocyte for enhanced cytokine production and in maintaining this "primed" state.

Actins↗

PubMedDate not supplied

Fractured aorta--a case report.

A 66-year-old, restrained driver involved in a high-speed motor vehicle crash sustained a transmural infrarenal fracture of a circumferentially calcified aorta. Blunt abdominal aortic injury is exceedingly rare, about twenty times less common than its thoracic counterpart, and the current case report is therefore unusual. A high index of suspicion in combination with a suggestive clinical history or examination should prompt diagnostic intervention, as both morbidity and mortality are high.

Accidents, Traffic↗