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Biomedical subjects

E E Moore

Publications and source records attributed to E E Moore.

At least 145 records · Page 8Linked to original sources
PubMed1996

Early risk factors for postinjury multiple organ failure.

Epidemiologic studies, based on retrospective data from heterogeneous populations with poor control of confounders, led early investigators to conclude that infection was the overriding risk factor for multiple organ failure (MOF). More recent studies have convincingly shown that MOF frequently occurs in the absence of infection. Consequently, we have shifted our research focus away from the traditional infectious models of MOF to the newer "one-hit" and "two-hit" inflammatory models. Clinically, we have chosen to study trauma patients because they are a relatively homogeneous group with a low incidence of common confounders. Trauma also permits a clear distinction between the first insult and the outcome, both temporally and with respect to the definition criteria. In this review we discuss the background, rationale, and our initial attempts to use indicators of the first insult (i.e., tissue injury quantification and clinical signs of shock) and indicators of the host response (i.e., systemic inflammatory response syndrome) to predict MOF early after injury.

Critical Care↗
PubMed1996

Involvement of bradykinin B1 and B2 receptors in human PMN elastase release and increase in endothelial cell monolayer permeability.

Bradykinin (BK) is a potent inflammatory mediator, which can release other inflammatory mediators by interacting with bradykinin B1 and B2 receptors. The role of kinins in regulating human PMN elastase release was studied. BK induced elastase release 5-fold over basal levels. Elastase release was inhibited by both B1 and B2 receptor antagonists. A specific B1 agonist des-Arg10-KD increased elastase release 4-fold. Since elastase has been implicated in vascular leak, the effect of BK on endothelial cell monolayer (EM) permeability was assessed. BK increased EM leak (I125 flux) across the EM, whereas des-Arg10-KD was inactive. When co-cultured with human umbilical vein endothelial cells, des-Arg10-KD-treated PMNs increased EM leak by 35%. The elastase inhibitor AAVPK blocked des-Arg10-KD-induced leak by 80% suggesting that elastase is responsible for the increase in permeability. It is concluded that BK causes increased leak by inducing PMN elastase release via activation of both B1 and B2 receptors. BK blockade and elastase inhibition may be beneficial in inflammatory diseases such as ARDS which is characterized by increased lung permeability and both kinin and PMN activation are thought to participate.

Amino Acid Chloromethyl Ketones↗
PubMed1996

Traumatic rupture of the descending thoracic aorta.

Traumatic rupture of the descending thoracic aorta is a highly lethal injury caused by sudden, rapid deceleration in high-speed motor vehicular collisions and falls from heights. Deceleration causes the mobile ascending aorta and aortic arch to move forward while the descending thoracic aorta remains fixed by the mediastinal pleura. This opposing movement creates a tear at the aortic isthmus just distal to the origin of the left subclavian artery. Patients with traumatic ruptured descending thoracic aortas often have serious multisystem injuries, and approximately 85% of these patients die at accident scenes or during emergency department resuscitation. The most frequent cause of death is free rupture of periaortic tissues that temporarily have provided tamponade to the sites of aortic ruptures. Surgical mortality rates for patients who survive initial resuscitation are between 10% and 25%. Advances in field triage and emergency medical transportation systems and new preoperative evaluation modalities have improved the survival of patients with traumatic descending thoracic aorta ruptures.

Adult↗
PubMed1996

Thomas G. Orr Memorial Lecture. Staged laparotomy for the hypothermia, acidosis, and coagulopathy syndrome.

The recent history, indications, physiologic objectives, and technical aspects of staged laparotomy are discussed in this overview. While postinjury refractory coagulopathy is the most common scenario for this life-saving concept, there are many other potential applications during both emergency and elective procedures in the neck, chest, pelvis, and extremities as well as the abdomen.

Abdominal Muscles↗
PubMed1996

Tracheal gas insufflation is a useful adjunct in permissive hypercapnic management of acute respiratory distress syndrome.

BACKGROUND: Despite numerous advances in critical care, the mortality of postinjury acute respiratory distress syndrome (ARDS) remains high. Recently, permissive hypercapnia (PHC) has been shown to be a viable alternative to traditional ventilator management in patients with ARDS. However, lowering tidal volume, as employed in PHC, below 5 cc/kg impinges upon anatomic dead space and precipitates a significant rise in PaCO2 The purpose of this study was to determine if continuous tracheal gas insufflation (cTGI) is a useful adjunct to PHC by lowering PaCO2, thus allowing adequate reduction in minute ventilation to achieve alveolar protection. METHODS: Over a 5-year period, 68 trauma patients with ARDS were placed on permissive hypercapnia. Nine of these patients additionally received cTGI at 7 L/min. Arterial blood gas determinations and ventilatory parameters were examined immediately prior to the implementation of cTGI and after 6h. RESULTS: The cTGI produced significant improvement in pH (7.25 +/- 0.03 to 7.33 +/- 0.03), PaCO2 (72 +/- 5 to 59 +/- 5 torr), tidal volume (7.9 +/- 0.6 to 7.2 +/- 0.6 cc/kg), and minute ventilation (13 +/- 1 to 11 +/- 1 L/min; P < 0.05). CONCLUSIONS: Continuous TGI is a useful adjunct to permissive hypercapnia, allowing maintenance of an acceptable pH and PaCO2 while allowing further reduction in tidal volume and minute ventilation.

Adolescent↗
PubMed1996

Jack A. Barney Resident Research Award winner. The inflammatory profile of interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 in postinjury multiple organ failure.

BACKGROUND: Interleukin-6 (IL-6), interleukin-8 (IL-8), and adhesion molecules have been implicated as mediators in neutrophil (PMN) and endothelial cell (EC) interactions leading to postinjury multiple organ failure (MOF). Our hypothesis was that circulating levels of IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) would discriminate patients at risk for postinjury MOF. METHODS: Serial plasma levels of IL-6, IL-8, and sICAM-1 were measured in 27 high-risk trauma patients. RESULTS: The IL-6 and IL-8 levels were significantly elevated in MOF patients compared with non-MOF patients at 12 and 36 hours postinjury. The IL-6 level was also elevated at 84 and 132 hours, and IL-8 at 84 hours. The sICAM-1 level did not become elevated in MOF patients until 132 hours postinjury. CONCLUSION: Interleukin-6 and IL-8 are elevated early after trauma and discriminate patients who will develop MOF. Late elevation of sICAM-1 likely results from PMN cytotoxicity leading to EC injury or inflammation.

Adult↗
PubMed1996

Soluble intercellular adhesion molecule-1 provokes polymorphonuclear leukocyte elastase release by CD18.

BACKGROUND: Elevated levels of soluble intercellular adhesion molecule-1 (sICAM-1) correlate with the development of postinjury multiple organ failure. Soluble ICAM-1 secretion is known to be induced in endothelial cells and monocytes by diverse inflammatory stimuli. We have found that incubation of quiescent polymorphonuclear leukocytes (PMNs) with sICAM-1 elicits elastase release and, more recently, that cross-linking CD18 receptors on PMNs also produces elastase release. Consequently, our study hypothesis was that sICAM-1 provokes PMN elastase release through its interaction with CD18. METHODS: To obtain sICAM-1, Chinese hamster ovarian cells transfected with human ICAM-1 were lysed and centrifuged at 150,000 g for 1 hour; the supernatant was passed over an ICAM-1 affinity column, eluted with 0.1 mmol/L glycine HCl, and concentrated with dialysis filter. Human PMNs (2.5 x 10(5)) were saturated with specific monoclonal antibodies for the beta 2 subunits (CD11a, CD11b, CD18) or nonspecific monoclonal antibodies for 30 minutes on ice before a 1-hour incubation with sICAM-1 (75 ng/ml) at 37 degrees C. Elastase activity was measured by the cleavage of n-methoxysuccinyl-A-A-P-V-p-nitroanilide. RESULTS: Neutrophil incubation with sICAM-1 resulted in 19.2% +/- 2.8% of total PMN elastase, compared with 2.4% +/- 0.5% in the controls. Blockade of CD18 abrogated sICAM-1 provoked elastase release with monoclonal antibodies to CD18 (TS1/18, 31H8) resulting in 4.3% +/- 1.0% and 5.5% +/- 1.4% elastase release, respectively. Blockade of CD11a, CD11b, and nonspecific antibody controls had no effect on sICAM-1 induced elastase release. CONCLUSIONS: In vitro, sICAM-1 provokes PMN elastase release through CD18. This may represent a mechanism by which elevated levels of circulating sICAM-1, released from local injury sites, provoke distal organ dysfunction.

Animals↗
PubMed1996

The abdominal compartment syndrome.

1. ACS is caused by an acute increase in intra-abdominal pressure, usually as a result of intra-abdominal hemorrhage. 2. The most common and significant complications are respiratory and renal failure. 3. Abdominal decompression promptly reverses the complications of ACS. 4. Failure to recognize and treat ACS is inevitably fatal.

Abdomen↗
PubMed1996

Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation?

OBJECTIVE: The effects of interleukin (IL)-6 in the injured patient are examined in an attempt to clarify the potential pathophysiologic role of IL-6 in the response to injury. SUMMARY BACKGROUND DATA: Interleukin-6 is an integral cytokine mediator of the acute phase response to injury and infection. However, prolonged and excessive elevations of circulating IL-6 levels in patients after trauma, burns, and elective surgery have been associated with complications and mortality. The mechanistic role of IL-6 in mediating these effects is unclear. METHODS: A review of current literature is performed to summarize the origins, mechanisms of action, and biologic effects of IL-6 and to characterize the IL-6 response to injury. RESULTS: Interleukin-6 is a multifunctional cytokine expressed by a variety of cells after a multitude of stimuli, under complex regulatory control mechanisms. The IL-6 response to injury is uniquely consistent and related to the magnitude of the insult. Moreover, the early postinjury IL-6 response correlates with complications as well as mortality. CONCLUSIONS: Interleukin-6 appears to play an active role in the postinjury immune response, making it an attractive therapeutic target in attempts to control hyperinflammatory provoked organ injury.

Antigens, CD↗
PubMed1996

An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome.

OBJECTIVE: No means exist for predicting the acute respiratory distress syndrome (ARDS), which complicates sepsis, trauma, and a variety of clinical disorders. Because activation of phospholipid-signaling pathways involving the acyl chains oleate and linoleate may initiate and amplify the inflammatory response, and thereby lead to the development of ARDS, we examined whether serum concentrations of these bioactive lipids increase and are predictive of ARDS in at-risk patients. DESIGN: Part I: A prospective, single-blind trial. Part II: A prospective, randomized, double-blind trial. SETTING: General intensive therapy units in five university teaching hospitals. SUBJECTS: Part I: Thirty-nine healthy control patients were studied to determine normal distribution of serum acyl values, followed by 30 patients admitted with onset of sepsis, trauma, or development of ARDS (within 24 hrs of admission) over a 1-yr period. Part II: Eight patients admitted with sepsis syndrome over a 2-month period. INTERVENTIONS: Part II: Patients were randomized to receive the substituted methylxanthine, lisofylline (CT1501R), or an identically presented placebo. MEASUREMENTS AND MAIN RESULTS: We measured the serum free fatty acid concentrations in the 39 healthy control subjects, and then we prospectively examined the serum free fatty acid concentrations in 30 age-matched patients in samples obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS. We then prospectively studied eight septic, at-risk patients who were matched for age, Acute Physiology and Chronic Health Evaluation II scores, Multiple Organ Failure index, and Glasgow Coma Score, in a double-blind, placebo-controlled, pilot study. These patients included four patients who received no treatment and four patients who received lisofylline, a compound that decreases serum unsaturated free fatty acids and diminishes acute lung injury in animals caused by sepsis and/or trauma. The calculated ratios of serum free fatty acids (Le., the ratio of C18 unsaturated fatty acids linoleate and oleate to fully saturated palmitate, C16:0) increased and predicted the development of ARDS in at-risk patients. Serum samples from the 30 patients, obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS, had significantly increased mean acyl chain ratios (1.42 +/- 0.35 [SD]) compared with healthy control subjects (0.86 +/- 0.25; p < .01). Sera from 13 patients with sepsis or trauma who did not develop ARDS (group A [at-risk, non-pre-ARDS]) also had increased acyl ratios (1.23 +/- 0.27) compared with sera from healthy control subjects (0.86 +/- 0.25; p < .01). Sera from seven patients who subsequently developed ARDS (group B [at-risk, pre-ARDS]) had higher acyl ratios (1.70 +/- 0.21) than group A at-risk patients who did not develop ARDS (1.23 +/- 0.27; p < .01) or healthy control subjects (0.86 +/- 0.25; p < .001). Sera from ten group C patients with ARDS at the time of admission to the study had the highest acyl ratios (1.80 +/- 0.75), which exceeded values for healthy control subjects (p < .001) and group A at-risk patients without ARDS (p = .01), but were not significantly different then group B at-risk, pre-ARDS patients (p = .17). Prospective study of eight septic, at-risk patients demonstrated significantly (p < .05) increased serum acyl ratios in the four untreated patients (findings consistent with the first study) but a significantly (p = .02) reduced ratio in the four at-risk patients treated with lisofyline. CONCLUSIONS: Increases in unsaturated serum acyl chain ratios differentiate between healthy and seriously iII patients, and identify those patients likely to develop ARDS. Thus, the serum acyl ratio may not only prospectively identify and facilitate the assessment of new treatments in patients at highest risk for developing ARDS, but may also lead to new insights about the pathogenesis of ARDS.

Adult↗
PubMed1996

Nuclear factor-kappa B is activated in alveolar macrophages from patients with acute respiratory distress syndrome.

OBJECTIVE: The expression of proinflammatory cytokines is rapidly increased in experimental models of the acute respiratory distress syndrome (ARDS), in patients at risk for ARDS, and in patients with established ARDS. Because multiple cytokines are present in bronchoalveolar lavage fluid, a common, proximal activation mechanism may operate in these settings. The proinflammatory cytokines whose expression is increased in the lungs of patients with ARDS have binding sequences in their enhancer/promoter regions for transcriptional regulatory proteins, such as nuclear factor-kappa B (NF-kappa B), nuclear factor-IL6 (NF-IL6), cyclic adenosine monophosphate responsive element binding protein, serum protein-1, and activating protein-1. To test the hypothesis that activation of one or more of these nuclear transcriptional regulatory factors might provide a common mechanism for the simultaneous expression of multiple cytokine genes in the setting of ARDS, we measured activation of these factors in alveolar macrophages from patients with ARDS and from controls. DESIGN: Prospective, clinical study. SETTING: Medical and surgical intensive care units at a university hospital and a county hospital. PATIENTS: Twelve patients, six with established ARDS and six control patients without lung injury. INTERVENTIONS: Patients with ARDS and controls underwent fiberoptic bronchoscopy and bronchoalveolar lavage. Alveolar macrophages were isolated from lavage fluid and the nuclear proteins were extracted. Activation of transcriptional factors NF-kappa B, NF-IL6, cyclic adenosine monophosphate responsive element binding protein, activating protein-1, and serum protein-1 was determined using an electrophoretic mobility shift assay, followed by densitometry of the autoradiographed gels. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in gender, age, tobacco smoking, Acute Physiology and Chronic Health Evaluation II score, quantity of lavage fluid, or number of alveolar macrophages in lavage specimens in the patient groups. Acute Lung Injury score and the Pao2/Fio2 ratio differed significantly between controls and ARDS patients: 0.46 +/- 0.17 vs. 2.74 +/- 0.14 (p < .0001) and 310 +/- 45 torr (41.3 +/- 6.0 kPa) vs. 150 +/- 11 torr (21.3 +/- 1.5 kPa) (p < .006), respectively. The mean Fio2 of the control patients was not significantly different from the mean Fio2 of ARDS patients: 0.47 +/- 0.11 vs. 0.55 +/- 0.6 (p = .53). Patients with ARDS had significantly (p < .02) increased activation of NF-kappa B in alveolar macrophages compared with patients without the syndrome. There was no evidence of increased activation of the transcriptional factors activating protein-1, serum protein-1, NF-IL6, or cyclic adenosine monophosphate responsive element binding protein in alveolar macrophages from ARDS vs. control patients. CONCLUSIONS: These experiments demonstrated increased in vivo activation of the nuclear transcriptional regulatory factor NF-kappa B (but not NF-IL6, cyclic adenosine monophosphate responsive element binding protein, activating protein-1, or serum protein-1) in alveolar macrophages from patients with ARDS. Because binding sequences for NF-kappa B are present in the enhancer/promoter sequences of multiple proinflammatory cytokines, activation of NF-kappa B may contribute to the increased expression of multiple cytokines in the lung in the setting of established ARDS.

Adult↗
PubMed1996

Endothelial cell activity varies in patients at risk for the adult respiratory distress syndrome.

OBJECTIVE: The endothelial cell produces many bioactive compounds that are presumed to play important roles in the pathogenesis of the adult respiratory distress syndrome (ARDS). We postulated that individuals with sepsis and trauma-two at-risk diagnoses for the development of ARDS--might demonstrate differences in the degree of endothelial cell activity. DESIGN: Prospective cohort study. SETTING: Intensive care unit patients in a tertiary, university-affiliated, city hospital. PATIENTS: Fifty-five intensive care unit patients (19 with sepsis and 36 trauma patients). INTERVENTIONS: Plasma measurements of three endothelial cell products--von Willebrand factor antigen, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble E-selectin-were performed within 8 hrs of patients meeting our inclusion criteria, and at the clinical onset of ARDS. MEASUREMENTS AND MAIN RESULTS: Twenty-six percent of the septic patients and 25% of the trauma patients developed ARDS. The median (and 25% to 75% quartiles) concentrations of all three mediators measured in the sepsis patients (von Willebrand factor antigen 399% [375% to 452%], ICAM-1 573 ng/mL [470 to 980], and soluble E-selectin 180 ng/mL [81 to 340]) were significantly higher (p < .001 for each individual analysis) than in the trauma patients (von Willebrand factor antigen 256% [217% to 310%], ICAM-1 148 ng/mL [113 to 210], and soluble E-selectin 42 ng/mL [31 to 65 ng/ mL]). In addition, neither the ICAM-1 nor soluble E-selectin concentrations measured in the trauma patients were different (p = .17 and p = .24, respectively) from normal controls. In those patients who developed ARDS, the differences in the concentrations of all three endothelial cell mediators between the sepsis and trauma patients persisted (p = .008 for von Willebrand factor antigen, p = .003 for ICAM-1, and p = .003 for E-selectin). CONCLUSION: These findings suggest that differences in endothelial cell activity exist between sepsis and trauma patients who are at risk for the development of ARDS.

Adult↗
PubMed1996

Postinjury multiple organ failure: a bimodal phenomenon.

To better define the epidemiology of postinjury multiple organ failure (MOF), we prospectively evaluated 457 high-risk trauma patients who survived more than 48 hours. Overall, 70 (15%) developed MOF. In 27 (39%) patients, the occurrence was early, while in 43 (61%) patients the presentation was delayed. At presentation, early MOF had more cardiac dysfunction, while late MOF had greater hepatic failure. Indices of shock were more critical risk factors for early MOF, while advanced age was more important for late MOF. While early and late MOF had a similar high incidence of major infections, these appeared to be more important in precipitating late MOF. Finally, while mortality is similar, early MOF patients appear to succumb faster. In conclusion, postinjury MOF remains a significant challenge and appears to present in at least two patterns (i.e., early versus late). Better understanding of the relative roles of the dysfunctional inflammation and infections in early MOF versus late MOF may facilitate the development of new strategies for the prevention and treatment of morbid syndrome.

Adolescent↗
PubMed1996

Interleukin-6 delays neutrophil apoptosis via a mechanism involving platelet-activating factor.

BACKGROUND: Interleukin (IL)-6, an integral mediator of the physiologic acute phase response to injury, has been associated with adverse postinjury complications when present in excessive concentrations. The precise role of IL-6 is unclear, but may involve exacerbation of polymorphonuclear neutrophil leukocytes (PMN)-mediated hyperinflammation. We have shown that IL-6 delays PMN apoptosis, thereby inhibiting the resolution of inflammation. More recently we have found that IL-6 stimulates PMNs to generate platelet-activating factor (PAF). Given the evidence for PAF involvement in postinjury hyperinflammation, we hypothesized that IL-6 delayed apoptosis via a mechanism involving PAF. METHODS: PMNs were isolated from healthy human donors using plasma-Percoll gradients and were cultured in enriched RPMI 1640 media at 2 x 10(7) PMNs/mL for 24 hours (37 degrees C, 5% CO2). Subgroups were treated with IL-6 (0.1-10 ng/mL) or PAF (0.1-10 ng/mL) or pretreated with the PAF receptor antagonist WEB 2170 (20 microM) before IL-6 or PAF. Morphologic assessment and quantitation of apoptosis was performed with acridine orange/ethidium bromide stain. RESULTS: Both IL-6 and PAF suppressed PMN apoptosis. Pretreating PMNs with WEB 2170 abrogated the effects IL-6 as well as PAF. CONCLUSION: Interleukin-6 delays PMN apoptosis via a mechanism involving PAF. These observations may help elucidate the mechanisms of IL-6 and PAF in mediating postinjury hyperinflammation and secondary organ dysfunction, ultimately leading to effective therapeutic targets in patients at risk for multiple organ failure.

Apoptosis↗