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Biomedical subjects

E E Moore

Publications and source records attributed to E E Moore.

At least 217 records · Page 12Linked to original sources
PubMed1994

Trauma primes cells.

Trauma induces many dramatic and complex changes in host cellular response. This complexity arises from the constellation of signals induced by stress, infection, and injury. Cellular priming, defined as altered response to an agonist induced by an antecedent stimulus, appears to be operative after trauma. If the interaction between two signalling pathways is such that one augments (or depresses) the other, subsequent stimulation of the second "primed" pathway can result in an exaggerated (or attenuated) response. Thus, trauma can prime cells in either a constructive or destructive fashion. Receptor stimulation by priming agents results in the activation of receptor-specific cell signalling pathways. These intracellular signalling pathways can "crosstalk" modifying each other in either a positive of negative fashion. The positive or negative character of interpathway crosstalk eventually manifests itself physiologically as constructive or destructive priming. Could the characteristics of the initial priming predict the sense of the final cellular message? Although the magnitude of both the priming stimulus and subsequent stimuli are important, the temporal relationship between the two stimuli as well as the positive or negative character of their interacting signal pathways need to be considered. It is unclear whether any one characteristic alone determines the sense of the priming effect. In general, it is the interaction of two stimuli with a cell at all three levels (magnitude, character, and temporal relationship) that dictates the final cellular response.

Animals↗
PubMed1994

Disparate signal transduction in neutrophil CD18 adhesion receptor expression versus superoxide generation.

BACKGROUND: We have previously shown that platelet-activating factor (PAF) primes polymorphonuclear neutrophils (PMNs) for superoxide generation and, concurrently, increases CD11/CD18 receptor expression; both events appear central to the pathogenesis of postinjury multiple organ failure. Recently, the counterinflammatory role of the neuroendocrine response to trauma has been emphasized, and, specifically, beta-adrenergic stimulation has been found to inhibit PMN activation. METHODS: Normal human PMNs were primed with PAF (10(-9) mol/L for 5 minutes) or pretreated with beta-receptor stimulation (isoproterenol, 10(-7) mol/L) or adenylate cyclase (AC) activation (forskoklin, 10(-7) mol/L) for 5 minutes and then primed with PAF. Superoxide generation in response to N-formyl-methionyl-leucyl-phenylalanine (10(-6) mol/L) was measured by superoxide dismutase inhibitable reduction of cytochrome C and CD18 expression determined by flow cytometry. RESULTS: PAF primed PMNs for superoxide generation (229.5 +/- 42.3 nmol/10(6) cells/min versus 18.7 +/- 6.5), whereas pretreatment with beta-adrenoreceptor stimulation (112.9 +/- 20.6) or AC activation (115.3 +/- 12.6) dramatically attenuated this process (p < 0.0001). PAF also enhanced CD18 expression (6.1 +/- 1.1 mean fluorescence intensity versus 10.3 +/- 2.3), but beta-adrenoreceptor stimulation (10.1 +/- 2.1) and AC activation (9.7 +/- 1.9) had no discernible effect. CONCLUSIONS: PAF priming of PMNs for superoxide generation was inhibited by the beta-adrenergic signal transduction pathway, but CD18 expression was not regulated via this pathway.

Adult↗
PubMed1994

Mandatory seatbelts: epidemiologic, financial, and medical rationale from the Colorado matched pairs study.

In what approximated a controlled clinical trial for efficacy of seatbelts, the Colorado matched pairs study examined 256 crashes meeting the following criteria: driver plus front-seat passenger, one belted (SB) and one nonbelted (NSB) occupant, and at least one occupant injured. Nearly half (119 of 256) of the SB partners escaped injury, while only 16% (41 of 256) of the NSB group were as fortunate. To ascertain a differential effect the 160 pairs discordant for injury were analyzed. The relative odds for injury in the SB group was 0.34 (95% Cl: 0.24, 0.49) of that in the NSB group. Likewise, relative odds for any medical costs in the SB group was reduced to 0.24 (95% Cl: 0.14, 0.43) and for hospitalization to 0.29 (95% Cl: 0.10, 0.80). Sixty-five percent of the SB group had no medical costs in contrast to only 29% of the NSB group. Altogether the NSB group accounted for 76% of the medical costs and 72% of the hospitalizations. This study establishes the effectiveness of seatbelts in reducing nonfatal injuries using epidemiologic, financial, and medical data.

Accidents, Traffic↗
PubMed1993

A recombinant human calcitonin receptor functions as an extracellular calcium sensor.

Calcitonin, a peptide hormone active in calcium homeostasis, is used in the treatment of bone loss disorders because it inhibits osteoclast function. A human calcitonin receptor was cloned and expressed in baby hamster kidney cells. Three independent stable transfectants respond to calcitonin via increased intracellular calcium ([Ca2+]i) and cyclic adenosine 3',5'-monophosphate (cAMP). We made the interesting observation that these cells also respond to millimolar increases in extracellular calcium via a rapid and sustained elevation in [Ca2+]i, whereas three calcitonin receptor-negative baby hamster kidney cell lines, two of which express recombinant receptors related to the calcitonin receptor, show no sensitivity to changes in extracellular calcium. The increase of [Ca2+]i in response to both calcitonin and extracellular calcium is a function of the average number of calcitonin receptors per cell. These studies suggest a dual role for the calcitonin receptor as a hormone receptor and an extracellular calcium sensor.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

Serum antioxidants as predictors of adult respiratory distress syndrome in patients with sepsis.

Adult respiratory distress syndrome (ARDS) can develop as a complication of various disorders, including sepsis, but it has not been possible to identify which of the patients at risk will develop this serious disorder. We have investigated the ability of six markers, measured sequentially in blood, to predict development of ARDS in 26 patients with sepsis. At the initial diagnosis of sepsis (6-24 h before the development of ARDS), serum manganese superoxide dismutase concentration and catalase activity were higher in the 6 patients who subsequently developed ARDS than in 20 patients who did not develop ARDS. These changes in antioxidant enzymes predicted the development of ARDS in septic patients with the same sensitivity, specificity, and efficiency as simultaneous assessments of serum lactate dehydrogenase activity and factor VIII concentration. By contrast, serum glutathione peroxidase activity and alpha 1Pi-elastase complex concentration did not differ at the initial diagnosis of sepsis between patients who did and did not subsequently develop ARDS, and were not as effective in predicting the development of ARDS. Measurement of manganese superoxide dismutase and catalase, in addition to the other markers, should facilitate identification of patients at highest risk of ARDS and allow prospective treatment.

Antioxidants↗
PubMed1993

Partial left heart bypass for thoracic aorta repair. Survival without paraplegia.

OBJECTIVE: Emergency repair of the torn descending thoracic aorta has been associated with an almost 15% incidence of paraplegia. The literature to date suggests that the incidence of paraplegia is not influenced by mechanical adjuncts to enhance distal aortic perfusion during cross-clamping and therefore, "clamp and sew" has been considered an acceptable technique. The purpose of the present study was to review our experience with repair of descending thoracic aortas using partial left heart bypass and to compare this favorable initial experience with the available data on the use of the heparinless centrifugal pump. DESIGN: A retrospective review of the routine use of partial left heart bypass in 16 consecutive patients with descending thoracic aorta disruptions. Results were compared with similar reports in the recent literature on trauma. SETTING: A level 1 trauma facility in the Denver, Colo, metropolitan area. PATIENTS: All patients with multisystem blunt trauma with a mean injury severity score of 36. INTERVENTION: Repair of the descending thoracic aorta disruption using partial left heart bypass with a heparinless centrifugal pump. MAIN OUTCOME MEASURES: Primary outcome measures were survival and paraplegia; other monitored variables included proximal and distal aortic pressure, flow rates, and oxygen transport. RESULTS: Among the 14 survivors (88%) there were no cases of paraplegia, and intraoperative hemodynamics and oxygen transport were well maintained with partial left heart bypass. This experience is added to the available reported data on the use of the centrifugal pump. In these additional 42 patients, the mortality rate was 7%, with no incidence of paraplegia. CONCLUSIONS: This collective experience failed to disclose a single case of paraplegia when partial left heart bypass was employed for repair of descending thoracic aorta. Moreover, the use of partial left heart bypass in this cohort of critically injured patients is associated with survival and perioperative morbidity rates comparable with the best recent reports of emergency thoracic aortic repair.

Abdominal Injuries↗
PubMed1993

Evidence for a central cholinergic effect of high-dose thiamine.

In vitro animal studies have suggested that thiamine is involved in the presynaptic release of acetylcholine. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetylcholine. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double-blind, placebo-controlled, double-crossover design. Drug effects were assessed by P3 event-related potential, quantitated electroencephalography, and free recall memory. Conditions included (1) baseline, (2) thiamine 5 gm p.o. and scopolamine 0.007 mg/kg IM, and (3) lactose PO and scopolamine 0.007 mg/kg IM. Thiamine significantly reduced adverse effects of scopolamine on P3 latency, spectral components of electroencephalography, and memory recall. The results are consistent with a cholinomimetic effect of thiamine in the central nervous system. Additional studies are needed to delineate the basic mechanisms and possible therapeutic efficacy of thiamine at pharmacological dosages.

Adult↗
PubMed1993

Gut ischemia mediates lung injury by a xanthine oxidase-dependent neutrophil mechanism.

Neutrophils (PMNs) are believed to play a key role in the pathogenesis of postinjury adult respiratory distress syndrome. We have previously shown that gut ischemia/reperfusion (I/R) produces lung injury by a process that requires PMNs. More recently, we have shown that xanthine oxidase (XO) plays a role. The purpose of this study was to characterize the mechanistic sequencing of XO activity versus the PMN in this model of gut I/R-induced lung injury. Normal and XO-inactivated (tungsten enriched, molybdenum depleted diet) rats underwent 45 min of superior mesenteric artery occlusion. After 6 hr reperfusion, blood was sampled and gut and lungs harvested. Myeloperoxidase (MPO) was used to quantitate PMN presence in the gut and lungs, while circulating PMN priming was measured as the difference in superoxide production with and without the activating stimulus, fMLP. 125I-labeled albumin leak was used as a marker for lung endothelial permeability. We observed that the gut I/R increased gut MPO levels, primed circulating PMNs, increased lung MPO levels, and provoked distant lung leak. XO inactivation abolished gut MPO activity, attenuated circulating PMN priming, and blocked lung leak. In conclusion, XO plays a proximal role in the pathogenesis of remote organ injury following splanchnic hypoperfusion.

Animals↗
PubMed1993

Pneumonia: cause or symptom of postinjury multiple organ failure?

Recent studies have shown that selective gut decontamination can reduce the incidence of pneumonia, but this does not decrease multiple organ failure (MOF) or mortality. These findings have prompted the hypothesis that pneumonia is an inconsequential symptom of MOF. To test this, we prospectively evaluated 123 high-risk trauma patients (mean Injury Severity Score = 36.2 +/- 1.5). Organ dysfunction, scored daily according to a 12-point scale, ultimately developed in 28 (23%) patients. Major infections were diagnosed, based on strict criteria, in 59 patients (48%), and pneumonia developed in 52 patients (43%). Pneumonia was significantly associated with MOF (82% of patients with MOF versus 30% of patients without MOF, p < 0.0001). In 14 (50%) of the patients with MOF, pneumonia preceded a significant rise (greater than or equal to 3) in serial MOF scoring. Of note, 10 (71%) of these patients died. Among the remaining 14 patients with MOF, 10 developed pneumonia, but this was associated with a minimal increase (less than or equal to 2) in MOF scoring (3 patients died). These data, by temporal association with MOF scoring, implicate pneumonia in precipitating or significantly worsening organ failure in 50% of the patients who developed MOF.

Adolescent↗
PubMed1993

The role of cholinergic systems in visuospatial processing and memory.

Few studies have specifically addressed the cholinergic role in visuospatial memory. In the present study, we employed a randomized double-blind repeated measures design to investigate the effects of scopolamine on Judgement of Line Orientation (JLO) and two distinct visuospatial memory tasks. Complex Figures (CF) is a test of drawn reproduction similar to the Rey complex figure. The Spatial Array Memory Test (SAMT) is a two-dimensional free-recall visuospatial test which minimizes constructive skills and allows sensitive measurement of placement errors. Scopolamine impaired performance on JLO and CF. However, no effects of scopolamine on SAMT were apparent even though the SAMT is sensitive to aging and right temporal-lobe lesions. Selective effects of scopolamine on focused versus distributed attention may account for these differential results.

Adult↗
PubMed1993

Comparison of intraosseous, central, and peripheral routes of crystalloid infusion for resuscitation of hemorrhagic shock in a swine model.

Venous access is often a clinical dilemma in severely hypovolemic children. This study compares fluid resuscitation by central vein, peripheral vein, and the intraosseous route in a hemorrhagic shock model. Hampshire piglets were bled to a mean arterial pressure of 30 mm Hg. This level of shock was sustained for 30 minutes. Resuscitation was carried out with normal saline delivered at 50 mL/min by a manual pressure of 450-475 mm Hg over the ensuing 20 minutes. Bone marrow from two intraosseous-infused animals was harvested immediately after the study for histologic examination. The hemodynamic response to crystalloid resuscitation was comparable among the three groups. There was no significant difference in mean arterial pressure, central venous pressure, cardiac output, pulmonary capillary wedge pressure, mixed venous oxygen saturation, or arterial oxygen saturation. Histologically, cellular washout and necrosis were found in bone marrow immediately adjacent to the intraosseous needle infusion site. For fixed-rate infusion, intraosseous crystalloid resuscitation is as efficacious as that delivered by peripheral or central venous routes in reversing hemorrhagic shock.

Animals↗
PubMed1993

Acute ethanol intoxication increases the risk of infection following penetrating abdominal trauma.

Acute alcohol (ETOH) intoxication as a risk factor for infection in trauma victims to our knowledge has not been previously reported. To determine if ETOH intoxication increases infection risk we examined data from 365 patients with penetrating abdominal trauma who were enrolled in a multi-center antibiotic study. Ninety-four patients sustained an injury to a hollow viscus. To separate acute from chronic ETOH effects, infections were divided into two categories: (1) trauma related; infections caused by bacterial contamination at the time of injury, while blood alcohol level (BAL) was elevated. (2) nosocomial; infections caused by bacteria acquired during hospital stay, after BAL had normalized. A BAL > or = 200 mg/dL was associated with a 2.6-fold increase in trauma-related infections. There was no association between BAL and subsequent nosocomial infection. Since infection rates for intoxicated patients were not higher after BAL had normalized, acute rather than chronic effects of ETOH appear to be responsible.

Abdominal Injuries↗
PubMed1993

Medicare's resource-based relative value scale fee schedule portends a gloomy future for trauma surgery.

Medicare's resource-based relative value scale (RBRVS) fee schedule dramatically restructures physician reimbursement; providers of cognitive-based services are projected to gain at the expense of those with procedure-based services. In this study, we computed the impact of the new payment system for Medicare comparing trauma surgery to four other surgical specialties. Plastic surgery will see a 4% increase in revenue, but the other specialties will experience a cut (trauma, minus 14%; general, minus 4%; vascular, minus 5%; cardiothoracic, minus 10%). As expected, with the exception of plastic surgery, there was a decrease in procedure reimbursement (trauma, minus 13%; general, minus 12%; vascular, minus 8%; cardiothoracic, minus 10%). However, when analyzing cognitive services, trauma is the only group that will sustain a reduction. This is largely explained by the fact that trauma cognitive services are inpatient based, whereas the RBRVS fee schedule is biased toward outpatient cognitive services. In conclusion, the RBRVS fee schedule will challenge the economic stability of trauma surgeons. Because Medicare reform will set future standards for other forms of physician reimbursement, trauma system planners need to take a proactive role in this evolving process.

Cardiac Surgical Procedures↗
PubMed1993

Pelvic fracture geometry predicts risk of life-threatening hemorrhage in children.

Recent studies have concluded that pelvic fractures in children, unlike those in adults, are not a source of life-threatening hemorrhage. Our study hypothesis was that major bleeding occurs in children with pelvic fractures, and fracture geometry allows early identification of patients at risk for severe hemorrhage. Fifty-seven (5.5%) of 1044 pediatric trauma patients sustained pelvic fractures. The majority of injuries were from motor vehicle crashes (n = 21, 36.8%) and auto-pedestrian collisions (n = 18, 31.6%). Twenty-three children (40.4%) had unilateral anterior fractures (type I), seven (12.2%) had unilateral posterior fractures (type II), 23 (40.4%) had unilateral anterior and posterior fractures (type III), and four (7%) had bilateral anterior and posterior (type IV) fractures. Eighteen children (32.6%) required blood transfusions during the initial 48 hours (mean, 59 mL/kg). Skeletal fixation was applied in ten patients (17.5%), and it controlled bleeding in six (60%). Pelvic angiography identified arterial hemorrhage in three of four patients, and embolization controlled bleeding in all cases. The only death in the series (mortality, 1.7%) was from multisystem trauma. Age, sex, Injury Severity Score, Revised Trauma Score, mechanism of injury, and pelvic fracture geometry were evaluated as risk factors predictive of hemorrhage employing multiple logistic regression. Only pelvic fracture geometry independently identified patients at increased risk of major bleeding. We conclude that pelvic fracture geometry identifies a subset of pediatric trauma patients at high risk for life-threatening hemorrhage and urge a prompt multispecialty approach to these patients.

Accidents, Traffic↗
PubMed1993

Diagnosing pneumonia in mechanically ventilated trauma patients: endotracheal aspirate versus bronchoalveolar lavage.

We prospectively investigated the diagnostic value of semiquantitative (semiQC) and quantitative (QC) cultures of endotracheal aspirate (ETA) compared with QC of bronchoalveolar lavage (BAL) fluids in 18 mechanically ventilated trauma patients with clinical signs of pneumonia. The general agreement between QC of ETA and BAL was 89% when conventional cutoffs for the QC were used and 94% if the cutoffs were adjusted for previous antibiotic therapy. In all six patients whose clinical diagnoses of pneumonia were considered definite, both QC of ETA and QC of BAL were positive; however, standard semiQC of ETA showed comparable results in this group. On the contrary, in the 12 patients whose clinical diagnoses were uncertain, QC of BAL and ETA were negative in ten patients and in five (50%) of these, pneumonia was eventually excluded. Semiquantitative cultures of ETA were positive in all these patients. Five (28%) patients experienced a decrease in PaO2/FiO2 (> 15% of previous value) 2 hours after BAL, and in three (17%) this derangement persisted for 24 hours. These data suggest that BAL may be hazardous in mechanically ventilated trauma patients and that its use should be restricted to patients in whom the diagnosis is in doubt.

Adult↗