Search PubMed⌕ Search

Biomedical subjects

F A Moore

Publications and source records attributed to F A Moore.

At least 91 records · Page 5Linked to original sources
PubMed1995

Epidemiology of trauma deaths: a reassessment.

OBJECTIVE: Recognizing the impact of the 1977 San Francisco study of trauma deaths in trauma care, our purpose was to reassess those findings in a contemporary trauma system. DESIGN: Cross-sectional. MATERIAL AND METHODS: All trauma deaths occurring in Denver City and County during 1992 were reviewed; data were obtained by cross-referencing four databases: paramedic trip reports, trauma registries, coroner autopsy reports and police reports. MEASUREMENTS AND MAIN RESULTS: There were 289 postinjury fatalities; mean age was 36.8 +/- 1.2 years and mean Injury Severity Score (ISS) was 35.7 +/- 1.2. Predominant injury mechanisms were gunshot wounds in 121 (42%), motorvehicle accidents in 75 (38%) and falls in 23 (8%) cases. Seven (2%) individuals sustained lethal burns. Ninety eight (34%) deaths occurred in the pre-hospital setting. The remaining 191 (66%) patients were transported to the hospital. Of these, 154 (81%) died in the first 48 hours (acute), 11 (6%) within three to seven days (early) and 26 (14%) after seven days (late). Central nervous system injuries were the most frequent cause of death (42%), followed by exsanguination (39%) and organ failure (7%). While acute and early deaths were mostly due to the first two causes, organ failure was the most common cause of late death (61%). CONCLUSIONS: In comparison with the previous report, we observed similar injury mechanisms, demographics and causes of death. However, in our experience, there was an improved access to the medical system, greater proportion of late deaths due to brain injury and lack of the classic trimodal distribution.

Accidents, Traffic↗
PubMed1995

CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion.

Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB2) is the integrin receptor on PMNs critical for adhesion-dependent oxidative burst. The purpose of this study was to investigate the mechanistic role of CD11b in the process of gut I/R-induced lung injury. Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery (SMA) occlusion with and without CD11b monoclonal antibody treatment (IB6) (1 mg/kg, i.v.), before SMA clamping. At 2-hour reperfusion, PMN presence in tissue was quantitated by myeloperoxidase activity and circulating PMN priming determined by the difference in superoxide production with and without N-formyl-methionyl-leucyl-phenylalanine, whereas lung leak was assessed by 125I-albumin lung/blood ratio. In sum, CD11b blockade prevented gut I/R-induced lung leak, but did not attenuate gut I/R-induced PMN priming or tissue PMN accumulation. In conclusion, gut I/R promotes PMN priming and PMN adhesion in both local and distant beds via receptors other than CD11b, but this B2 integrin receptor is critical for PMN-mediated endothelial injury.

Animals↗
PubMed1995

Interleukin-8 increases endothelial permeability independent of neutrophils.

Interleukin-8 (IL-8) has been associated with a variety of hyperinflammatory states and adverse clinical events. Circulating IL-8 levels correlate with the severity of tissue trauma, and excessive elevations of IL-8 are associated with postinjury adult respiratory distress syndrome and multiple organ failure. While IL-8 is a potent neutrophil (PMN) chemoattractant and activator and enhances PMN transendothelial migration, it also acts to inhibit PMN adhesion to stimulated endothelial cells (ECs). We hypothesized that IL-8 could interact directly with ECs to increase permeability independent of PMNs. Human umbilical vein ECs (HUVECs) were cultured on collagen-coated micropore filters, and integrity of the EC monolayer measured by albumin flux across the filter. Cytochalasin D was used as a positive control. IL-8 induced increased permeability at a concentration of 1000 ng/mL. This effect was abrogated by preincubation of HUVECs with a protein synthesis inhibitor (cycloheximide). These data suggest a role for IL-8 in promoting endothelial leak independent of PMNs, via a mechanism involving protein synthesis.

Cell Membrane Permeability↗
PubMed1995

Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure.

Polymorphonuclear neutrophils (PMNs) play a pivotal role in the inflammation that precedes multiple organ failure (MOF). In a rat model of MOF, PMNs become primed for enhanced superoxide anion (O2-) release and CD11b expression, sequester in end organs, and produce organ failure. Therefore, we hypothesized that circulating PMNs harvested in the first 24 hours after injury from trauma patients at risk for MOF would (1) exhibit a primed O2- release, (2) upregulate CD11b expression, and (3) show evidence of sequestration in tissues. Extracellular PMN O2- release and CD11b receptor expression were measured at 3, 6, 12, and 24 hours after injury in 33 torso trauma patients with Injury Severity Scores > 15; eight patients (24%) developed MOF. Healthy adults served as controls. PMNs after injury were primed for enhanced in vitro O2- release at 3, 6, 12, and 24 hours after injury, indicating prior in vivo priming. CD11b expression was also increased at 6, 12, and 24 hours after injury. Circulating PMN numbers increased sharply at 3 hours after injury, before decreasing dramatically at 6 and 12 hours, suggesting end organ sequestration. At 12 hours after injury, declines in circulating PMNs were significantly greater in MOF than in non-MOF patients (p < 0.05). These data indicate that PMNs are quickly mobilized into the circulation after injury and then primed for enhanced O2- release and CD11b expression. PMN priming appears to be a necessary preamble to PMN sequestration in patients with major torso trauma. Upregulation of PMN function, accompanied by subsequent end organ sequestration, may represent an important early event in the pathogenesis of MOF after injury.

Adult↗
PubMed1995

Inhaled nitric oxide variably improves oxygenation and pulmonary hypertension in patients with acute respiratory distress syndrome.

OBJECTIVE: The purpose of this study was to determine the effect of inhaled nitric oxide (NO) on oxygenation, hemodynamics, and ventilation in patients with adult respiratory distress syndrome (ARDS). METHODS: Sixteen trials of inhaled NO were performed in 14 ARDS patients (age 42.9 +/- 6) who had significant pulmonary hypertension (mean pulmonary artery pressure > 30 mm Hg). Patients were monitored with arterial and pulmonary artery catheters. Volume ventilation was performed by a strict protocol. Data were collected at baseline and 30 minutes after 20 and 40 ppm NO. RESULTS: Overall, the Pao2/FIO2 ratio increased from 69.5 +/- 3.9 to 100.8 +/- 9.5 at 20 ppm, a 42.9 +/- 8.7% increase, and to 97.7 +/- 13.1 at 40 ppm, a 44.1 +/- 14.2% increase over baseline (p = 0.001). However, 5/16 trials demonstrated minimal improvement (Pao2/FIO2 ratio increase < 20%), 5 moderate improvement (20-50%), and 6 marked improvement (> 50%). Overall the mean pulmonary artery pressure (MPAP) decreased from 41.1 +/- 1.8 mm Hg to 34.3 +/- 1.3 at 20 ppm and 33.5 +/- 1.8 mm Hg at 40 ppm, a 15.0 +/- 3.7% decrease, p = 0.002. However, 5/16 trials demonstrated minimal improvement (MPAP decrease < 10%), 7 moderate improvement (10-20%), and 4 marked improvement (> 20%). At 40 ppm NO, 4 patients with moderate improvement in MPAP at 20 ppm NO had marked improvement. There were no changes in systemic oxygen delivery and consumption, intrapulmonary shunt, or lung compliance at 20 or 40 ppm (p > 0.05). Following collection of these data, prolonged NO inhalation (2-20 ppm) was done in 10 of 14 patients for 4.5 +/- 0.7 days (range 1-10 days). Overall, there were 7 deaths (mortality 50%). In patients receiving prolonged NO, there were 3 deaths (mortality 30%). All 4 patients who failed to respond to inhaled NO subsequently died (mortality 100%). CONCLUSIONS: Inhaled NO improves oxygenation and pulmonary hemodynamics in patients with ARDS. However, the improvement to NO is variable.

Adolescent↗
PubMed1995

Portal triad injuries.

OBJECTIVE: Injuries to the portal triad are a rare and complex challenge in trauma surgery. The purpose of this review is to better characterize the incidence, lethality, and successful management schemes used to treat these injuries. DESIGN: A retrospective review of the experience of eight academic level I trauma centers over a combined 62 years. RESULTS: A retrospective review of the experience of eight anatomical structures of the portal hepatis: 118 injuries to the anatomical structures of the portal hepatis: 55 extrahepatic portal vein injuries, 28 extrahepatic arterial injuries, and 35 injuries to the extrahepatic biliary tree. Sixty-nine percent of the injuries were by penetrating mechanism and 31% were by blunt mechanism. All patients had associated injuries with a mean Injury Severity Score of 34 in blunt trauma patients. Overall mortality was 51%, rising to 80% in patients with combination injuries. Sixty-six percent of deaths occurred in the operating room, primarily from exsanguination; 18% of deaths occurred within 48 hours of injury from refractory shock, coagulopathy, or cardiac arrest; 16% occurred late. Ten percent of patients undergoing portal vein ligation survived, compared to 58% managed by primary repair. Survival after hepatic artery ligation was 42%, compared to 14% after primary repair. Survival after biliary-enteric anastomosis as treatment of extrahepatic bile duct injury was 89%, compared to 50% after primary repair and 100% after ligation of lobar bile duct injuries. Missed bile duct injuries had a high (75%) severe complication rate. CONCLUSIONS: Injuries to the anatomical structures of the portal triad are rare and often lethal. Intraoperative exsanguination is the primary cause of death, and hemorrhage control should be the first priority. Bile duct injuries should be identified by intraoperative cholangiography and repaired primarily or by enteric anastomosis; lobar bile ducts can be managed by ligation.

Adolescent↗
PubMed1995

Postinjury neutrophil priming and activation states: therapeutic challenges.

Both hyperactivity and hypoactivity of neutrophils (PMNs) have been implicated in the pathogenesis of postinjury multiple organ failure. In this paper, the cellular and molecular mechanisms involved in the regulation of PMN O2- production are reviewed. In addition, relevant research laboratory techniques for measuring both intracellular and extracellular O2- release are outlined. In a pilot study PMN O2- release in response to a battery of PMN agonists was determined, and four functional states of the NADPH were defined: resting, primed, activated, and unresponsive. PMNs from normal adult volunteers are in the resting state. In contrast, PMNs from patients with severe torso trauma are primed and activated in the first 24 h postinjury, but, after 48 h, become unresponsive to both receptor-dependent (platelet activating factor and N-formyl-methyl-leucyl-phenylalanine) and receptor-independent (phorbol 12-myristate 13-acetate) activation. The ability to identify at-risk patients and provide a rationale for ameliorating PMN-mediated tissue injury in patients with hyperinflammation syndromes are discussed. In addition, the importance of identifying patients with PMNs that are unresponsive, and the necessity for increasing PMN function in these patients in order to reduce the risk of sepsis, are also discussed.

Humans↗
PubMed1995

Gut phospholipase A2 mediates neutrophil priming and lung injury after mesenteric ischemia-reperfusion.

Intestinal ischemia-reperfusion (I/R) provokes polymorphonuclear neutrophil (PMN)-mediated lung injury via a process characterized by circulating PMN priming, pulmonary PMN sequestration, and increased microvascular leak in the lung. We found in rats subjected to intestinal I/R (ischemia 45 min and reperfusion 6 h) that 1) intestinal phospholipase A2 (PLA2) was activated during ischemia, 2) circulating PMN priming (assessed by superoxide production with N-formyl-Met-Leu-Phe) occurred after 1 h reperfusion, and 3) exaggerated 125I-labeled albumin lung leak occurred after 2 h reperfusion, compared with sham-treated animals (P < 0.05). Treatment with a PLA2 inhibitor, quinacrine, within 15 min of reperfusion reversed the exaggerated gut PLA2 activity and abrogated subsequent PMN priming and lung leak (P < 0.05). However, when quinacrine was administered after 2 h of reperfusion, circulating PMN priming and lung leak continued to evolve despite suppression of intestinal PLA2 activity. We conclude that intestinal PLA2 activation may be a prerequisite for the sequelae of circulating PMN priming and pulmonary microvascular leak observed after intestinal I/R.

Animals↗
PubMed1995

Quantifying oxidative injury in the liver.

Oxidative injury is a mechanism common to both ischemia-reperfusion (IR) and leukocyte-mediated injury. Reperfused tissue beds and elaborated mediators can activate a cascade of intercellular and interorgan injuries that often precipitates multiple organ failure. Initiation of lung injury by gut IR is a case in point, but concomitant liver injury may have been overlooked because of the absence of comparably sensitive physiological markers. In this study, we explore the hypothesis that occurrence of portally derived oxidant-induced liver dysfunction may be detected with both sensitivity and specificity. We simulated pure oxidative injury to the liver and separated the contributions from secondary systemic oxidation. Both tissue and plasma indicators were evaluated, each reflecting aspects of oxidation, membrane integrity, and metabolic function. Tissue markers readily detect oxidative liver injury, but systemic 3-hydroxybutyrate (3-OHB) concentration and ketone body ratio (KBR) are the most sensitive. Comparison of 3-OHB concentrations against the corresponding KBR can be used to distinguish adjustments within a physiological range from the transition into injury.

3-Hydroxybutyric Acid↗
PubMed1995

von Willebrand factor antigen levels are not predictive for the adult respiratory distress syndrome.

In patients with nonpulmonary sepsis, von Willebrand factor antigen (vWF:Ag or Factor VIIR:Ag) levels have been reported to be predictive for the development of the adult respiratory distress syndrome (ARDS). We addressed the ability to generalize these results by measuring serial Factor vWF:Ag levels in 96 patients at risk for the development of ARDS. Patients with sepsis, pancreatitis, hypertransfusion, witnessed aspiration of gastric contents, abdominal trauma, chest trauma, and multiple fractures were studied. Sequential measurements were obtained at enrollment into the study (T = 0), and T = 6, 12, 24, and 48 h. Subjects were grouped into sepsis and nonsepsis categories and analyzed according to the following outcome definitions: ARDS and non-ARDS. The mean values for the sepsis and nonsepsis groups were elevated above normal at all time points. A statistically significant difference occurred in the mean vWF:Ag level for the ARDS and non-ARDS patients in the nonsepsis group at T = 0 (p = 0.05). To assess the clinical utility of these results, ROC (receiver operating characteristics) curves were plotted at T = 0, and optimal cutoff values of vWF:Ag were determined. In the sepsis group, the best value for vWF:Ag above which patients would actually develop ARDS was 399%, resulting in a 70% sensitivity and a 47% specificity. For the non-sepsis patients, the optimal value was 273%, yielding a sensitivity of 64% and a specificity of 52%. We conclude that measuring vWF:Ag levels are not helpful in predicting the progression to ARDS in multiple at-risk patients.

Adult↗
PubMed1995

Neutrophil response to endotoxin in the adult respiratory distress syndrome: role of CD14.

The role of both endotoxin and neutrophils in the development of acute lung injury continues to be debated. We hypothesized that early in the course of the development of the adult respiratory distress syndrome (ARDS) circulating neutrophils could be primed by endotoxin and that subsequent stimulated responses could be enhanced. Accordingly, neutrophils were isolated from patients at risk for and with ARDS. Unstimulated neutrophils from these patients neither produced nor were primed for superoxide production. Whereas phorbol myristate acetate-stimulated superoxide production was preserved, indicating that the cells were capable of a response, patient neutrophils produced less superoxide than did cells from normal subjects when primed with endotoxin (lipopolysaccharide [LPS]) and stimulated with formyl-methionyl-leucine-phenylalanine (FMLP), suggesting that there was a defect in the signal transduction mechanism for LPS. This was confirmed by the finding that patient neutrophils also had both decreased baseline CD14 expression and less CD14 upregulation after LPS stimulation compared with neutrophils from normal subjects. The mechanisms that could account for the decreased CD14 expression were studied in vitro. Neutrophils from normal subjects both upregulate CD14 in response to LPS and shed CD14 over time, suggesting that in patients CD14 receptors could have been previously upregulated and shed. In addition, there is an association between CD14 expression and retention such that normal LPS-stimulated neutrophils which are not retained in a filtration system have decreased CD14 expression. Thus, in patients, those PMN most responsive to LPS could be preferentially sequestered and not available in the circulation for study.

Adult↗
PubMed1995

Clinical benefits of early post-injury enteral feeding.

Over the past two decades, clinical studies have provided convincing evidence that early nutritional support benefits metabolically stressed surgical patients by preventing acute protein malnutrition. However, the optimal route of substrate delivery (ie, enteral versus parenteral) continues to be debated. Recent basic and clinical investigation offers the exciting possibility that the beneficial effects of traditional nutritional support can be amplified by supplementing specific nutrients that exert pharmacological immune-enhancing effects. Over the past 15 years, the Department of Surgery at the Denver General Hospital has focused clinical research efforts on defining optimal nutrition following major torso trauma. The purpose of this paper is to review our studies as well as other clinical studies in order to answer three questions: 1) Does early post-injury nutritional support improve patient outcome? 2) What is the preferred route of substrate delivery? 3) Do new 'immune-enhancing' diets offer additional clinical benefits?

Enteral Nutrition↗
PubMed1994

Early predictors of postinjury multiple organ failure.

OBJECTIVE: To find a predictive model for postinjury multiple organ failure (MOF). DESIGN: A 3-year cohort study ending December 1992 (first year: retrospective; last 2 years: prospective). SETTING: Denver General Hospital (Colo) is a regional level I trauma center. PATIENTS: Consecutive trauma patients with an Injury Severity Score (ISS) greater than 15, with an age greater than 16 years, and who survived longer than 24 hours. Stepwise logistic regression analysis was performed in all patients (n = 394), in the subgroup of patients with 0 to 12 hours, plus 12 to 24 hours base deficit (BD) results (n = 220), and in a second subgroup of patients with BD plus lactate results at 0 to 12 hours and 12 to 24 hours (n = 106). MAIN OUTCOME: Postinjury MOF. RESULTS: The following variables were identified as independent predictors of MOF in the analysis of all patients: age more than 55 years, ISS greater than or equal to 25, and more than 6 U of red blood cells in the first 12 hours after admission (U RBC/12 hours). In the subgroup with BD results, the same analysis identified age greater than 55 years, greater than 6 U RBC/12 hours, and BD greater than 8 mEq/L (0 to 12 hours), while in the last subgroup analysis including BD and lactate results, greater than 6 U RBC/12 hours, BD greater than 8 mEq/L (0 to 12 hours), and lactate greater than 2.5 mmol/L (12 to 24 hours) were independently associated with MOF. CONCLUSIONS: Age greater than 55 years, ISS greater than or equal to 25, and greater than 6 U RBC/12 hours are early independent predictors of MOF. Subgroup analyses indicate that BD and lactate levels may add substantial predictive value. Moreover, these results emphasize the predominant role of the initial insult in the pathogenesis of postinjury MOF.

Adolescent↗
PubMed1994

Interleukin-6 potentiates neutrophil priming with platelet-activating factor.

BACKGROUND: Polymorphonuclear neutrophil (PMN) priming appears to be an important event in the pathogenesis of hyperinflammatory states, resulting in adult respiratory distress syndrome or multiple organ failure. Interleukin-6 (IL-6) is an integral mediator of the acute stress response to injury and infection, but excessive and prolonged systemic levels have been associated with morbidity and mortality following trauma, burns, and elective surgery. We hypothesized that IL-6 primed PMNs for exaggerated cytotoxicity. However, we have been unable to directly prime PMNs for superoxide release with IL-6. OBJECTIVE: To determine whether IL-6 acted in concert with another inflammatory mediator (platelet-activating factor [PAF]) to prime PMNs. METHODS: Polymorphonuclear neutrophils isolated from healthy human donors were incubated for varying times with IL-6 (0.01 to 100 ng/mL), PAF (0.01 to 100 ng/mL), or a combination of IL-6 and PAF. Superoxide production was then measured with and without the addition of the PMN-activating formylpeptide formyl-methionyleucylphenylalanine. RESULTS: Over the range of times (5 to 90 minutes) and doses tested, IL-6 did not prime PMNs, while PAF primed PMNs in a dose- and time-dependent manner. Interleukin 6 (10 ng/mL) combined with a nonpriming concentration of PAF (0.1 ng/mL) primed PMNs for superoxide production over a range of incubation times. CONCLUSION: The inflammatory mediators IL-6 and PAF act synergistically to prime PMNs in vitro. This observation may begin to elucidate the mechanistic role of IL-6 in pathologic clinical states.

Analysis of Variance↗
PubMed1994

Endotoxin pretreatment inhibits neutrophil proliferation and function.

Gut ischemia/reperfusion (I/R) induces lung injury by a mechanism that involves neutrophils (PMNs). We have previously shown that endotoxin (LPS), when administered after gut I/R, amplifies this lung injury, while treatment with LPS prior to gut I/R prevents lung injury. The purpose of this study was to determine whether LPS pretreatment (Pre Rx) alters the PMN inflammatory component of the gut I/R injury. Specifically, we focused on whether LPS Pre Rx effected (i) PMN stem cell proliferation, (ii) gut I/R-induced PMN priming, and (iii) gut I/R-induced PMN lung sequestration. Bone marrow was harvested from normal and LPS-pretreated (0.5 mg/kg, ip, 3 days prior) rats, and colony forming units--granulocyte/macrophage (CFU-GM) were quantitated using a soft agar culture technique. In another experiment, normal and LPS-pretreated rats were subjected to gut I/R (45 min superior mesenteric artery occlusion/6 hr reperfusion), and blood and lungs were then harvested. The in vivo priming of PMN was assessed by measuring the difference in superoxide production (O2-) with and without the activating stimulus, N-formylmethionyl-leveyl-phenylalanine (fMLP). The quantity of myeloperoxidase (MPO) was used as an index of the number of PMN sequestered in lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Gut ischemia induces bone marrow failure and increases risk of infection.

Hemorrhagic shock leads to bone marrow (BM) failure and renders the host susceptible to infection. We hypothesized that splanchnic hypoperfusion may play a mechanistic role in this process. BM was harvested from normal rats and, on Postprocedure Days 1 and 3, from rats that had undergone laparotomy (LAP) or gut ischemia/reperfusion (I/R; 45 min superior mesentery artery occlusion). Granulocyte-macrophage colony-forming unit (CFU-GM) proliferation, a measure of BM myeloid progenitors, was quantitated using a standard soft agar culture technique. On Postprocedure Days 1 and 3, BM proliferation of CFU-GM was depressed in gut I/R rats, compared to control and LAP animals (P < 0.05). Next, six rats were subjected to I/R, LAP, ANEST (anesthesia control), or no treatment (NL, normal control); 1 day later, 3.5 x 10(7) Staphylococcus aureus, suspended in 0.25 ml of saline, were injected subcutaneously in four sites on the back of each animal. Five days later, the NL rats had developed 23 abscesses, ANEST 23, and LAP 22, while the gut I/R rats had 24. The abscesses were excised, weighed, and measured. The weight and size of abscesses were greater in the gut I/R animals (P < 0.05). In summary, gut I/R depressed BM proliferation and rendered animals susceptible to infection in a manner similar to that observed following hemorrhagic shock. These data suggest that splanchnic hypoperfusion, a common sequela of hemorrhagic shock, may play a mechanistic role in BM failure and infection after hemorrhage.

Abscess↗
PubMed1994

A critical analysis of acutely injured children managed in an adult level I trauma center.

The triage of all injured children to regional pediatric trauma centers may be impractical and unnecessarily exclude adult level I trauma centers from the care of the acutely injured child. The purpose of this study was to critically evaluate the outcome of injured children treated in an adult level I trauma center by adult trauma surgeons. The records of 410 consecutively treated children (age < or = 15 years) and 188 young adults (age 16 to 18 years) admitted to the trauma service during a 2-year period (ending December 1991) were studied. The probability of survival was calculated using TRISS methodology. Results were analyzed using the Z statistic, permitting objective comparison with national norms (Major Trauma Outcome Study). Severity of injury (RTS and ISS) was equivalent (P > .05) in children and young adults. The observed survival (98.0%) in children compared favorably with the predicted survival (TRISS) of 97.7%. Calculation of the Z statistic showed no difference in outcomes of acutely injured children (+0.47) relative to young adults (+0.45) or national norms (MTOS). The triage of injured children to an adult level I trauma center does not adversely affect outcome. Subset analysis of injured children showed no differences in observed outcome relative to predicted outcome (national control) or outcome in young adults (institutional control). These data support the continued triage of acutely injured children to regional trauma centers regardless of pediatric or adult designation.

Acute Disease↗