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Biomedical subjects

E E Moore

Publications and source records attributed to E E Moore.

At least 37 records · Page 2Linked to original sources
PubMed2001

Plasma from aged stored red blood cells delays neutrophil apoptosis and primes for cytotoxicity: abrogation by poststorage washing but not prestorage leukoreduction.

BACKGROUND: Blood transfusion-particularly that of older stored red blood cells (RBCs)--is an independent risk factor for postinjury multiple organ failure. Immunomodulatory effects of RBC transfusion include neutrophil (PMN) priming for cytotoxicity, an effect exacerbated by longer RBC storage times. We have found that delayed PMN apoptosis in trauma patients is provoked by transfusion, independent of injury severity. We hypothesized that aged stored RBCs delay PMN apoptosis, but that prestorage leukodepletion or poststorage washing could abrogate the effect. METHODS: Healthy volunteers each donated 1 unit of blood. One half was leukodepleted, and RBC units were processed in the usual fashion and stored at 4 degrees C. Aliquots were removed on days 1, 14, 21, and 42 and the plasma fraction isolated. Selected aliquots were washed with normal saline before plasma isolation. PMNs harvested from healthy controls were incubated (5% CO2, 37 degrees C) with unmodified, leukoreduced, or washed RBC plasma (20% plasma/80% RPMI 1640), and apoptosis assessed by morphology after 24 hours. Apoptotic index (apoptotic PMNs/total PMNs) was compared. PMN priming for superoxide release was also assessed after plasma exposure. RESULTS: PMN apoptosis was delayed by RBCs stored for 21 or 42 days. Prestorage leukodepletion did not alter the effect. However, washing 42-day-old RBCs abrogated the effect. PMN priming for superoxide was provoked by stored packed RBCs in an identical pattern to delayed apoptosis. CONCLUSION: Plasma from stored RBCs-even if leukoreduced-delays apoptosis and primes PMNs. The effect becomes evident at 21 days and worsens through product outdate (42 days), but may be prevented by poststorage washing. Inflammatory agents contaminating stored blood likely mediate the effect. Modification of transfusion practices (e.g., giving fresher or washed RBCs or blood substitutes) may attenuate adverse immunomodulatory effects of transfusion in trauma patients.

Analysis of Variance↗
PubMed2001

Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function.

BACKGROUND: Resuscitation with oxygen-carrying fluids is critically important in the patient with hemorrhagic shock caused by trauma. However, it is clear that a number of biologic mediators present in stored blood (packed red blood cells [PRBCs]) have the potential to exacerbate early postinjury hyperinflammation and multiple organ failure through priming of circulating neutrophils (PMNs). PolyHeme (Northfield Laboratories, Evanston, IL), a hemoglobin-based substitute that is free of priming agents, provides an alternative. We hypothesized that PMN priming would be attenuated in patients resuscitated with PolyHeme in lieu of stored blood. METHODS: Injured patients requiring urgent transfusion were given either PolyHeme (up to 20 units) or PRBCs. Early postinjury PMN priming was measured via beta-2 integrin expression, superoxide production, and elastase release. RESULTS: Treatment groups were comparable with respect to extent of injury and early physiologic compromise. PMNs from patients resuscitated with PRBCs showed priming in the early postinjury period by all three measures. No such priming was evident in patients resuscitated with PolyHeme. CONCLUSION: The use of a blood substitute in the early postinjury period avoids PMN priming and may thereby provide an avenue to decrease the incidence or severity of postinjury multiple organ failure.

Blood Pressure↗
PubMed2001

Penetrating colon injuries requiring resection: diversion or primary anastomosis? An AAST prospective multicenter study.

BACKGROUND: The management of colon injuries that require resection is an unresolved issue because the existing practices are derived mainly from class III evidence. Because of the inability of any single trauma center to accumulate enough cases for meaningful statistical analysis, a multicenter prospective study was performed to compare primary anastomosis with diversion and identify the risk factors for colon-related abdominal complications. METHODS: This was a prospective study from 19 trauma centers and included patients with colon resection because of penetrating trauma, who survived at least 72 hours. Multivariate logistic regression analysis was used to compare outcomes in patients with primary anastomosis or diversion and identify independent risk factors for the development of abdominal complications. RESULTS: Two hundred ninety-seven patients fulfilled the criteria for inclusion and analysis. Overall, 197 patients (66.3%) were managed by primary anastomosis and 100 (33.7%) by diversion. The overall colon-related mortality was 1.3% (four deaths in the diversion group, no deaths in the primary anastomosis group, p = 0.012). Colon-related abdominal complications occurred in 24% of all patients (primary repair, 22%; diversion, 27%; p = 0.373). Multivariate analysis including all potential risk factors with p values < 0.2 identified three independent risk factors for abdominal complications: severe fecal contamination, transfusion of > or = 4 units of blood within the first 24 hours, and single-agent antibiotic prophylaxis. The type of colon management was not found to be a risk factor. Comparison of primary anastomosis with diversion using multivariate analysis adjusting for the above three identified risk factors or the risk factors previously described in the literature (shock at admission, delay > 6 hours to operating room, penetrating abdominal trauma index > 25, severe fecal contamination, and transfusion of > 6 units blood) showed no statistically significant difference in outcome. Similarly, multivariate analysis and comparison of the two methods of colon management in high-risk patients showed no difference in outcome. CONCLUSION: The surgical method of colon management after resection for penetrating trauma does not affect the incidence of abdominal complications, irrespective of associated risk factors. Severe fecal contamination, transfusion of > or = 4 units of blood within the first 24 hours, and single-agent antibiotic prophylaxis are independent risk factors for abdominal complications. In view of these findings, the reduced quality of life, and the need for a subsequent operation in colostomy patients, primary anastomosis should be considered in all such patients.

Adult↗
PubMed2001

Mesenteric lymph is responsible for post-hemorrhagic shock systemic neutrophil priming.

BACKGROUND: Hemorrhagic shock-induced splanchnic hypoperfusion has been implicated as a priming event in the two event model of multiple organ failure (MOF). We have previously shown that early postinjury neutrophil (PMN) priming identifies the injured patient at risk for MOF. Recent in vitro studies have demonstrated that postshock mesenteric lymph primes isolated human neutrophils. We hypothesize that lymphatic diversion before hemorrhagic shock abrogates systemic PMN priming and subsequent lung injury. METHODS: Sprague-Dawley rats (n >or= 5 per group) underwent hemorrhagic shock (MAP 40 mm Hg x 30 min) and resuscitation (shed blood + 2x crystalloid) with and without mesenteric lymphatic duct diversion. Sham animals underwent anesthesia and laparotomy. Whole blood was taken 2 hours after resuscitation, heparinized, and incubated for 5 min at 37 degrees C. Surface expression of CD11b (a marker for PMN priming) was determined by flow-cytometry compared with isotype controls. In addition, lung myeloperoxidase (MPO) was measured for PMN sequestration, and Evans blue lung leak was assessed in the bronchoalveolar lavage fluid in sham, and shock +/- lymph diversion animals. RESULTS: Hemorrhagic shock resulted in increased surface expression of PMN CD11b relative to sham (23.8 +/- 6.7 vs. 9.9 +/- 0.6). Mesenteric lymphatic diversion before hemorrhagic shock abrogated this effect (8.0 +/- 2.6). Lung PMN accumulation, as assessed by MPO, was greater in the lungs of nondiverted (113 +/- 14 MPO/mg lung) versus sham (55 +/- 4 MPO/mg lung, p < 0.05); lymph diversion reduced lung PMNs to control levels (71 +/- 6.5 MPO/mg lung, p < 0.05). Evans blue lung leak was 1.6 times sham in the hemorrhagic shock group; this was returned to sham levels after lymph diversion (p < 0.05). CONCLUSION: Post-hemorrhagic shock mesenteric lymph primes circulating PMNs, promotes lung PMN accumulation, and provokes acute lung injury. Lymphatic diversion abrogates these pathologic events. These observations further implicate the central role of mesenteric lymph in hemorrhagic shock-induced lung injury. Characterizing the PMN priming agents could provide insight into the pathogenesis of postinjury MOF and ultimately new therapeutic strategies.

Animals↗
PubMed2001

Blood transfusion and the two-insult model of post-injury multiple organ failure.

Neutrophils (PMNs) have been implicated in the pathogenesis of multiple organ failure (MOF). The two-insult model of MOF is based on the fundamental concept that two sequential and independent insults that are individually innocuous against the host can cause overwhelming inflammation. The in vitro PMN priming/activation sequence simulates the two-insult model. Our work has demonstrated that transfusion is an early consistent risk factor for post-injury MOF and lysophosphatidylcholines (lyso-PCs) are generated in stored blood components. Additionally, platelet-activating factor (PAF) is a key inflammatory agent produced in severely injured patients. We therefore hypothesize that two events, trauma and transfusion, enhance PMN cytotoxicity irrespective of the sequence. Superoxide (O2-) production was measured by reduction of cytochrome c, adherence to fibrinogen was assessed by the radioactivity of adherent Na2(51)CrO4 (51Cr)-labeled PMNs, and endothelial cell (EC) damage by measuring the radioactivity released from 51Cr-labeled human umbilical vein endothelial cells monolayers. Isolated PMNs were primed with buffer, PAF (2 microM), or lyso-PCs (4.5, 15, and 30 microM) followed by activation with buffer, N-formyl-methionyl-leucyl-phenylalanine (fMLP) (1 microM), PAF (2 microM), or lyso-PCs (4.5, 15, and 30 microM). Neither PAF nor lyso-PCs alone stimulated O2- production. While PAF alone caused PMN adherence, lyso-PCs alone did not allowed PMNs to adhere to fibrinogen. However, both combinations of PAF/lyso-PCs and lyso-PCs/PAF significantly augmented O2- production and PMN adherence. Furthermore, these enhanced PMN cytotoxic responses significantly caused EC damage. These findings suggest that in the scenario of the two-insult model, early or late transfusion administered following trauma can provoke PMN cytotoxicity via priming or activation, thereby increasing the risk of post-injury MOF.

Blood Preservation↗
PubMed2001

Post-hemorrhagic shock mesenteric lymph lipids prime neutrophils for enhanced cytotoxicity via phospholipase A2.

Hemorrhagic shock induced mesenteric hypoperfusion has long been implicated as a key event in the pathogenesis of the adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Previous work links post-hemorrhagic shock mesenteric lymph (PHSML) lipids and neutrophil (PMN) priming in the pathogenesis of ARDS. We hypothesize that gut phospholipase A2 (PLA2) liberates proinflammatory lipids following hemorrhagic shock, which are responsible for enhanced PMN cytotoxicity. Mesenteric lymph was collected from rats (n > or = 5) before hemorrhagic shock, during hemorrhagic shock (MAP 40 mm Hg x 30 min), and after resuscitation (shed blood + 2x lactated Ringers). PMNs were incubated with physiologic concentrations (1-5%, v:v) of (a) buffer control, (b) sham (c) pre-shock lymph, (c) PHSML, (d) PHSML lipid extracts, (e) heat-denatured PSHML, and (f) PHSML harvested after i.v. pretreatment with a known PLA2 inhibitor (quinacrine, 10 mg/kg). PMNs were activated with fMLP (1 micromol), and the maximal rate of superoxide production measured by reduction of cytochrome c. Gut morphology was assessed histologically using hematoxalin and eosin (HE) staining. PHSML and PHSML lipid extracts (5%, v:v) primed for enhanced superoxide production compared to buffer controls (2.5-fold and 3.6-fold), sham (2.5-fold) and pre-shock lymph (2.0-fold). Lymph collected after systemic PLA2 inhibition, in contrast, abrogated the PMN priming response. Gut mucosal morphology, at end-resuscitation, was intact on HE staining both with and without PLA2 inhibition. Heat denaturing the PHSML (eliminating cytokines and complement), on the other hand, did not reduce PMN priming. Physiologic concentrations of PHSML lipids prime the PMN respiratory burst. Lymph priming is diminished with systemic PLA2 inhibition, implicating gut PLA2 as a source of proinflammatory lipids that may be central in the pathogenesis of hemorrhagic shock induced ARDS/MOF.

Animals↗
PubMed2001

Hypertonic saline activation of p38 MAPK primes the PMN respiratory burst.

Investigation of hypertonic saline (HTS) modulation of neutrophils (PMN) cytotoxic responses has generated seemingly contradictory results. Clinically relevant levels of HTS attenuate receptor-mediated p38 MAPK signaling, whereas higher levels activate p38 MAPK. Concurrently, HTS exerts a dose-dependent attenuation of the PMN respiratory burst, most notably at concentrations where p38 MAPK is activated. We hypothesized that HTS-mediated p38 MAPK activation augments the PMN respiratory burst on return to normotonicity. We found that although clinically relevant levels of HTS (Na+ > or = 200 mM) did not activate p38 MAPK, higher concentrations (Na+ > or = 300 mM) resulted in activation comparable with that after PAF stimulation. Transient stimulation with high levels of HTS primed the PMN respiratory burst in response to fMLP and PMA. This effect was attenuated by pretreatment with SB 203580, a p38 MAPK specific inhibitor. We conclude that severe osmotic shock primes the respiratory burst via p38 MAPK signaling, further supporting the role of this signaling cascade in PMN priming.

Cells, Cultured↗
PubMed2000

Feasibility of damage control surgery in the management of military combat casualties.

Unique and expanded applications of staged operative management are undergoing careful evaluation in many civilian level I trauma centers under the rubric of damage control surgery. Recently there have been advocates for its broad application to the early management of critically injured combat casualties. However, the enormous logistic requirements for such strategies are contrary to the demands of the usual wartime scenario. On the basis of experience in civilian trauma centers and combat casualty management, we question the suggested extensive role of damage control surgery during wartime. Each decision point in damage control surgery should be analyzed as it is altered (sensitivity analysis) by conditions of war. It is unwise to adopt such indications unchanged from current civilian trauma policy.

Abdominal Injuries↗
PubMed2000

Maximal human neutrophil priming for superoxide production and elastase release requires p38 mitogen-activated protein kinase activation.

HYPOTHESIS: Neutrophil priming has been implicated in the development of multiple organ failure, although the precise intracellular mechanisms that regulate neutrophil priming remain unclear. Our previous work characterized platelet-activating factor (PAF) priming of human neutrophils for concordant superoxide anion (O2-) generation and elastase degranulation. The p38 mitogen-activated protein kinase (MAPK) is activated by PAF stimulation. We hypothesized that PAF-induced human neutrophil priming for O2- and elastase release is mediated via the p38 MAPK pathway. DESIGN: Isolated neutrophils from 6 human donors were preincubated with the specific p38 MAPK inhibitor SB 203580 (1 micromol/L) or buffer (control) for 30 minutes. Cells were then primed with PAF (200 nmol/L), followed by receptor-dependent (N-formyl-methionyl-leucyl-phenylalanine, 1 micromol/L) or receptor-independent phorbol myristate acetate (PMA, 100 ng/mL) activation. SETTING: Urban trauma research laboratory. PATIENTS: Healthy volunteer donors of neutrophils. MAIN OUTCOME MEASURES: Maximal rate of O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by the cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide. RESULTS: SB 203580 significantly attenuated the generation of O2- and release of elastase from neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine but not with PMA. Independent of the activator receptor status, SB 203580 almost completely blocked the exaggerated neutrophil cytotoxic response due to PAF priming. CONCLUSIONS: The p38 MAPK pathway is required for maximal PAF-induced neutrophil priming for O2- production and elastase degranulation. Therefore, the MAPK signaling cascade may offer a potential therapeutic strategy to preempt global neutrophil hyperactivity rather than attempt to nullify the end products independently.

Enzyme Activation↗
PubMed2000

Optimal management of complicated empyema.

BACKGROUND: Despite continued improvement in medical therapy, empyema remains a challenging problem for the surgeon. Multiple treatment options are available; however, the optimal therapeutic management has not been elucidated. METHODS: A retrospective review was performed of all adult patients admitted to Denver Health Medical Center between January 1, 1993, and December 31, 1998, with the diagnosis of empyema. Data tabulated included patient demographics, presentation, chest computed tomography (CT) findings, treatment, and outcome. RESULTS: Empyema was diagnosed in 58 patients, 45 cases of which were multiloculated at the time of presentation. Empyema was secondary to pneumonia is 41 patients and posttraumatic in 15. In addition to antibiotic therapy, initial treatment included chest tube drainage alone (n = 6), chest tube drainage with primary operation (n = 19), and chest tube drainage with intrapleural fibrinolytic therapy (n = 33). In 15 patients (45%), fibrinolytic therapy failed. Initial chest CT revealed a pleural peel in 5 patients treated with fibrinolytics and all failed. Multiloculation, however, was not a factor in failure of fibrinolysis. Moreover, chest CT missed the presence of a pleural peel in 17 of 31 patients documented to have a significant peel at the time of thoracotomy. CONCLUSION: Multiple therapeutic options are available for the management of empyema. Multiloculation is not a contraindication to an initial trial of chest tube drainage or fibrinolytic therapy. In contrast, CT evidence of a pleural peel uniformly predicted failure of nonoperative treatment.

Adult↗
PubMed2000

Limb and hemispatial hypometria.

In a previous study, we demonstrated that unilateral cerebral lesions produce hypometric limb movements of the contralateral arm and hemispatial (i.e., directional) hypometria for movements towards contralateral hemispace. In the present study, we investigated 10 patients with right cerebral lesions and 25 healthy controls using a task to uncouple deficits in sensory perceptual systems and motor-action output systems on directional hypometria. This task required participants, with their eyes closed, to reproduce lateral and medial horizontal displacements (15-27 cm) with each arm. Each participant was seated at a waist high table and had their hand placed at an origin point aligned with the axillary fold on the same side. Their hand was moved by the investigator from the origin point to a target point and brought back to the point of origin (input displacement). The participant was then asked to return their hand to either the same target point or to an equidistant target point in the opposite direction. Healthy dextral participants were significantly more hypometric with their right arm, but patients with right cerebral lesions exhibited an opposite pattern with overall left arm hypometria. In addition, patients were significantly more hypometric for movements when output displacements were toward left hemispace. No effect was found for direction of sensory input. The results suggest that the directional hypometria is predominantly produced by hemispatial output deficits.

Adolescent↗
PubMed2000

Isolated rupture of the cisterna chyli after blunt trauma.

An 8-year-old boy was evaluated for blunt abdominal trauma after a motor vehicle crash. In the course of his workup, a computed tomography (CT) scan of the abdomen was suspicious for a duodenal injury. At surgery, the duodenum was found to be normal; however, a rupture of the cisterna chyli was identified. This injury was repaired, and the boy made an uneventful recovery. This report is one of few in the literature describing isolated injury to the cisterna chyli after blunt abdominal trauma.

Abdominal Injuries↗
PubMed2000

Cervical spine trauma in the injured child: a tragic injury with potential for salvageable functional outcome,.

BACKGROUND/PURPOSE: Cervical spine injuries are uncommon in children, and, therefore, presumptive immobilization and diagnosis remain controversial. The purpose of this study was to review the author's experience with cervical spine injuries in children to determine the incidence, injury mechanism, pattern of injury, and subsequent functional outcome. METHODS: Fifty-two children over a 6-year period (1994 to 1999) with a cervical spine injury secondary to blunt trauma were identified (1.3% incidence). The functional independent measure (FIM) was assessed at the time of discharge in each of 3 categories: communication, feeding, and locomotion. RESULTS: Mean age of the study children was 10.7 +/- 0.7 years. Eight children (15%) were less than 5 years old, and 4 (8%) were less than 2 years old. The mechanism of injury included motor vehicle crash (52%), falls (15%), bicycle accidents (11%), sports-related injuries (10%), pedestrian accidents (8%), and motorcycle crashes (4%). Seven patients died yielding an overall mortality rate of 13%. Injuries were distributed along the cervical spinal cord as follows: 5 atlanto-occipital dislocations, 28 C1 to C3 injuries, 17 C4 to C7 injuries, and 2 ligamentous injuries. FIM scores were recorded for 18 patients. Seventeen communicated independently, 14 fed themselves independently, and 12 had independent locomotive function. CONCLUSIONS: Cervical spine injuries occur in children across a spectrum of ages. Although atlanto-occipital dislocation is a highly lethal event, children with C1 to C7 injuries have a high likelihood of reasonable independent functioning.

Adolescent↗