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Biomedical subjects

Raul Coimbra

Publications and source records attributed to Raul Coimbra.

At least 19 recordsLinked to original sources
PubMed2007

Trauma systems.

The major goal of a trauma system is to enhance the community health. This occurs through a process of assessment, policy development, and ongoing assurance. This can be achieved by (1) identifying risk factors in the community and creating solutions to decrease the incidence of injury, (2) providing optimal care during the acute and the late phase of injury, including rehabilitation, and (3) maintaining the objective to decrease overall injury-related morbidity and mortality and years of life lost. Disaster preparedness also is an important function of trauma systems, and using an established trauma system network facilitates the care of victims of natural disasters or terrorist attacks.

Emergency Medical Services↗
PubMed2007

Hypertonic saline and pentoxifylline reduces hemorrhagic shock resuscitation-induced pulmonary inflammation through attenuation of neutrophil degranulation and proinflammatory mediator synthesis.

BACKGROUND: Ringer's lactate (RL), the current standard resuscitation fluid, potentiates neutrophil activation and is associated with pulmonary inflammation. Resuscitation with hypertonic saline and pentoxifylline (HSPTX) has been shown to attenuate hemorrhagic shock-induced injury when compared with RL. Because the neutrophil plays a major role in postshock inflammation, we hypothesized that HSPTX reduces pulmonary inflammation after resuscitation in comparison to RL. METHODS: Sprague-Dawley rats underwent controlled shock and were resuscitated with RL (32 mL/kg) or HSPTX (4 mL/kg 7.5% NaCl + pentoxifylline 25 mg/kg). Animals who did not undergo shock or resuscitation served as controls. After 24 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Cytokine induced neutrophil chemoattractant (CINC) was measured in BALF by enzyme-linked immunosorbent assay. Matrix metalloproteinases (MMP)-2 and -9 were measured by zymography. Hemeoxygenase-1 (HO-1) was assessed by Western blot and immunohistochemistry. RESULTS: HSPTX resuscitation led to a 62% decrease in CINC levels compared with RL (p < 0.01). BALF MMP-2 expression was attenuated by 11% with HSPTX (p = 0.09). Lung MMP-2 and MMP-9 expression was reduced by 89% (p < 0.01) and 76%, respectively (p < 0.05). Lung HO-1 expression declined by 34% with HSPTX in comparison to RL (p < 0.01), indicating less oxidative injury. Lung immunohistochemistry localized HO-1 to neutrophils, macrophages, and airway epithelial cells. CONCLUSION: Collectively, the attenuation of pulmonary inflammation with HSPTX after shock when compared with RL is associated with downregulation of neutrophil activation, oxidative stress, and proinflammatory mediator production.

Animals↗
PubMed2007

Practice patterns and outcomes of retrievable vena cava filters in trauma patients: an AAST multicenter study.

BACKGROUND: The purpose of this study is to describe practice patterns and outcomes of posttraumatic retrievable inferior vena caval filters (R-IVCF). METHODS: A retrospective review of R-IVCFs placed during 2004 at 21 participating centers with follow up to July 1, 2005 was performed. Primary outcomes included major complications (migration, pulmonary embolism [PE], and symptomatic caval occlusion) and reasons for failure to retrieve. RESULTS: Of 446 patients (69% male, 92% blunt trauma) receiving R-IVCFs, 76% for prophylactic indications and 79% were placed by interventional radiology. Excluding 33 deaths, 152 were Gunter-Tulip (G-T), 224 Recovery (R), and 37 Optease (Opt). Placement occurred 6 +/- 8 days after admission and retrieval at 50 +/- 61 days. Follow up after discharge (5.7 +/- 4.3 months) was reported in 51%. Only 22% of R-IVCFs were retrieved. Of 115 patients in whom retrieval was attempted, retrieval failed as a result of technical issues in 15 patients (10% of G-T, 14% of R, 27% of Opt) and because of significant residual thrombus within the filter in 10 patients (6% of G-T, 4% of R, 46% Opt). The primary reason R-IVCFs were not removed was because of loss to follow up (31%), which was sixfold higher (6% to 44%, p = 0.001) when the service placing the R-IVCF was not directly responsible for follow up. Complications did not correlate with mechanism, injury severity, service placing the R-IVCF, trauma volume, use of anticoagulation, age, or sex. Three cases of migration were recorded (all among R, 1.3%), two breakthrough PE (G-T 0.6% and R 0.4%) and six symptomatic caval occlusions (G-T 0, R 1%, Opt 11%) (p < 0.05 Opt versus both G-T and R). CONCLUSION: Most R-IVCFs are not retrieved. The service placing the R-IVCF should be responsible for follow up. The Optease was associated with the greatest incidence of residual thrombus and symptomatic caval occlusion. The practice patterns of R-IVCF placement and retrieval should be re-examined.

Adult↗
PubMed2006

Neutrophil degranulation and the effects of phosphodiesterase inhibition.

BACKGROUND: Neutrophils play a major role as the first line in host defense after exposure to bacterial products. However, an exaggerated inflammatory response characterized by overwhelming neutrophil activation can be injurious to the host. Pentoxifylline (PTX), a nonspecific phosphodiesterase inhibitor, has been shown to attenuate neutrophil oxidative burst and decrease proinflammatory mediator synthesis. We hypothesized that PTX down-regulates neutrophil activation by decreasing the surface expression of both CD35 and CD66b, two markers of neutrophil degranulation. MATERIALS AND METHODS: Venous blood was obtained from three healthy volunteers. Whole blood was incubated with HBSS (control), f-methionyl-leucyl-phenylalanine (fMLP, 1 microM/L), PTX (2 mM/L), or fMLP + PTX. CD35 and CD66b expression were measured by flow cytometry. RESULTS: fMLP treatment caused a significant increase in CD35 and CD66b expression of when compared to controls (P < 0.01). PTX treatment revealed expression of both markers comparable to the control group. A 38% decrease in CD35 (64 +/- 12 versus 100; P < 0.01) and a 52% decrease in CD66b (48 +/- 7 versus 100; P < 0.01) expression were demonstrated in the fMLP + PTX group when compared to fMLP alone. CONCLUSION: In addition to the known effects of PTX on neutrophil oxidative burst, PTX also affects neutrophil degranulation, an essential step in enzyme release and subsequent tissue injury. These findings may have clinical relevance in the treatment of disease processes due to inflammation in which primed neutrophils play a role.

Adult↗
PubMed2006

Pentoxifylline attenuates stored blood-induced inflammation: A new perspective on an old problem.

BACKGROUND: Blood transfusion is a risk factor for many inflammatory processes. Its supernatant fraction has been proven to activate neutrophils. We hypothesized that pentoxifylline (PTX) would attenuate stored blood-induced neutrophil activation and pro-inflammatory mediator production. METHODS: Whole blood was incubated with HBSS, LPS (100 microg/mL), leukoreduced PRBC supernatant + LPS, or supernatant + LPS + PTX (2 mmol/L). TNF-alpha levels were measured by ELISA. MMP-9 was evaluated with zymography. Neutrophil CD66b expression was determined by flow cytometry in blood treated with HBSS, fMLP (1 micromol/L), supernatant + fMLP, or supernatant + fMLP + PTX. RESULTS: TNF-alpha levels were elevated in both the LPS and supernatant + LPS groups (100%; P < 0.01 and 120%; P < 0.01, respectively). PTX administration resulted in a 106% decrease in TNF-alpha (P < 0.0001). MMP-9 levels were increased in all groups. Administration of PTX to the supernatant + LPS group generated a 33% decrease in MMP-9 levels, which was not statistically significant (P < 0.4). Upregulation of CD66b expression was seen in LPS and supernatant + LPS groups. Significant attenuation was seen with PTX (47%; P < 0.01). CONCLUSIONS: PTX downregulates CD66b and TNF-alpha expression in supernatant-induced whole blood. Because blood transfusion can contribute to inflammatory injury, the adjunctive use of PTX may have therapeutic potential.

Antigens, CD↗
PubMed2006

Modulation of lipopolysaccharide-induced acute lung inflammation: Role of insulin.

The present study was undertaken to investigate the influence of insulin on lipopolysaccharide (LPS)-induced acute lung injury. Diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 30 days) and controls were instilled with saline containing LPS (750 microg/0.4 mL) or saline alone. The following analyses were performed 6 h there after: (a) total and differential cell counts in bronchoalveolar lavage (BAL) fluid, (b) quantification of tumor necrosis factor alpha, interleukin (IL) 1beta, IL-10, and cytokine-induced neutrophil chemoattractant 1 in the BAL (enzyme-linked immunosorbent assay), (c)immunohistochemistry for intercellular adhesion molecule 1 and E-selectin on lung vessels, and (d) quantification of metalloproteinases (MMP) 2 and 9 in the BAL (zymography). Relative to controls, diabetic rats exhibited a reduction in the number of neutrophils (80%) and reduced concentrations of tumor necrosis factor alpha (56%), IL-1beta (66%), and IL-10 (35%) after LPS instillation. Cytokine-induced neutrophil chemoattractant 1 levels did not differ between groups. Increased levels of MMP-2 (90%) and MMP-9 (500%) were observed in diabetic rats compared with controls. Treatment of diabetic rats with neutral protamine Hagedorn insulin (4 IU, s.c.), 2 h before LPS instillation, completely restored the number of neutrophils and concentrations of cytokines in the BAL fluid. Despite no significant differences between diabetic and control groups, there was a remarkable increase in intercellular adhesion molecule 1 and E-selectin expression on lung vessels after insulin treatment. Levels of MMP-2 and MMP-9 did not change after treatment with insulin. Levels of corticosterone were equivalent among groups. Data presented suggest that insulin modulates the production/release of cytokines and the expression of adhesion molecules controlling, therefore, neutrophil migration during the course of LPS-induced acute lung inflammation.

Animals↗
PubMed2006

Intraluminal pancreatic serine protease activity, mucosal permeability, and shock: a review.

Shock states are characterized by a pronounced activation of numerous cell types that lead to an acute inflammatory reaction. The exact mechanism by which these inflammatory cells are activated is not known. Numerous studies have implicated the gastrointestinal tract as one of the main sites for the generation of inflammatory mediators and initiation of an acute systemic response. The pancreas is known to secrete powerful digestive enzymes, and we hypothesize that they may play a leading role in the pathogenesis of multiorgan failure after the onset of shock. We carried out a search in PubMed for all relevant studies related to the role of the pancreas in shock. Studies that included information concerning the role of pancreatic enzymes in shock were then summarized. Our article serves to review the current hypotheses on how digestive enzymes produced by the pancreas may play a pivotal role in initiating the systemic inflammatory response. We further hypothesize how these enzymes and/or their products may ultimately contribute to multiorgan failure and death.

Animals↗
PubMed2006

HSPTX protects against hemorrhagic shock resuscitation-induced tissue injury: an attractive alternative to Ringer's lactate.

BACKGROUND: Conventional fluid resuscitation with Ringer's lactated (RL) activates neutrophils and causes end-organ damage. We have previously shown that HSPTX, a combination of small volume hypertonic saline (HS) and pentoxifylline (PTX), a phosphodiesterase-inhibitor, downregulates in vitro neutrophil activation and proinflammatory mediator synthesis. Herein, we hypothesized that HSPTX decreases end-organ injury when compared with RL in an animal model of hemorrhagic shock. METHODS: Sprague-Dawley rats were bled to a mean arterial pressure of 35 mm Hg for 1 hour. Animals were divided into 3 groups: sham (no shock, no resuscitation, n = 7), RL (32 mL/kg, n = 7), and HSPTX (7.5% NaCl 4 mL/kg + PTX 25 mg/kg; n = 7). Shed blood was infused after fluid resuscitation. Blood pressure was monitored until the end of resuscitation. Animals were sacrificed at 24 hour after resuscitation. Bronchoalveolar lavage fluid (BALF) was obtained for white cell count (total and differential) and TNF-alpha and IL-1beta levels were measured by ELISA. Lung and intestinal injury at 24 hour were evaluated by histopathology. Organ damage was graded by a pathologist and a score was created (0 = no injury; 3 = severe). Lung neutrophil infiltration was evaluated by MPO immune staining. RESULTS: There were no differences in mean arterial pressure between groups. At 24 hours, BALF leukocyte count was decreased by 30% in HSPTX animals (p < 0.01). TNF-alpha and IL-1beta levels were markedly decreased in HSPTX-resuscitated animals compared with their RL counterparts (p < 0.01). HSPTX-resuscitated animals (lung injury score = 1.0 +/- 0.4) had markedly decreased acute lung injury compared with RL-treated animals (2.5 +/- 0.3) (p < 0.01). RL resuscitation led to a two-fold increase in lung neutrophil infiltration whereas in HSPTX-treated animals, the number of MPO + cells was similar to sham animals (p < 0.001). Intestinal injury was markedly attenuated by HSPTX (1.1 +/- 0.3) compared with RL animals (2.6 +/- 0.4) (p < 0.001). CONCLUSIONS: HSPTX, a small volume resuscitation strategy with marked immunomodulatory potential led to a marked decrease in end-organ damage. HSPTX is an attractive alternative to RL in hemorrhagic shock resuscitation.

Animals↗
PubMed2006

LPS-induced acute lung injury is attenuated by phosphodiesterase inhibition: effects on proinflammatory mediators, metalloproteinases, NF-kappaB, and ICAM-1 expression.

BACKGROUND: Acute endotoxemia is characterized by an enhanced inflammatory response. Pentoxifylline (PTX), a phosphodiesterase inhibitor, has been shown to decrease TNF-alpha levels and to down-regulate neutrophil activation, likely because of increases in intracellular cyclic AMP. Its effects on lipopolysaccharide (LPS) induced lung injury, more specifically on tissue neutrophil infiltration and degranulation, adhesion molecule expression, and transcriptional factor activation, have not been fully investigated. We postulated that PTX treatment in acute endotoxemia downregulates the inflammatory response and may decrease lung injury. METHODS: Male Sprague-Dawley rats were randomized into three groups: Sham (saline i.v.), LPS (5 mg/kg i.v.), and PTX + LPS (25 mg/kg and 5 mg/kg i.v., respectively; concomitant injection). After 4 hours, bronchoalveolar lavage fluid (BAL), plasma, and lungs were sampled. BAL IL-8 (ELISA), BAL MMP-2, plasma MMP-9, and BAL MMP-9 (Zymography) were measured. Lung histology (H&E), in addition to lung MPO, ICAM-1, and NF-kappaB expression evaluated by immunohistochemistry were analyzed. Lung NF-kappaB DNA binding was evaluated by electrophoretic mobility shift assay. RESULTS: PTX treatment decreased BAL IL-8 levels, BAL MMP-2, and plasma MMP-9 activity. Lung neutrophil infiltration (MPO), ICAM-1 expression and NF-kappaB activation were decreased by PTX. In addition, PTX treatment caused a marked attenuation of LPS-induced lung injury. CONCLUSIONS: Phosphodiesterase inhibition by PTX attenuates LPS-induced end-organ injury. In addition, proinflammatory cytokine production is also downregulated, likely because of the marked attenuation of NF-kappaB DNA binding and activation.

Animals↗
PubMed2005

Phosphodiesterase inhibition attenuates stored blood-induced neutrophil activation: a novel adjunct to blood transfusion.

BACKGROUND: Activated neutrophils play a central role in the pathogenesis of ARDS and multiple organ failure (MOF). Transfusion of packed red blood cells (PRBCs) is an independent risk factor in the development of ARDS and MOF. It has been postulated that factors present in the supernatant of PRBCs activate neutrophils. The magnitude of neutrophil activation is dependent on the age of the stored blood. Our laboratory and others have reported that pentoxifylline (PTX), a nonspecific phosphodiesterase inhibitor, decreases neutrophil activation. We hypothesized that adding PTX to PRBCs would attenuate blood transfusion-induced neutrophil activation. STUDY DESIGN: Peripheral blood was obtained from healthy human volunteers. Oxidative burst, CD11b, and CD35 expression were measured by flow cytometry using a whole blood preparation. Whole blood was incubated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) (1 microM) alone and 42-day-old PRBC supernatant + fMLP with or without PTX (2 mmol/L). RESULTS: N-formyl-methionyl-leucyl-phenylalanine alone caused a significant increase in neutrophil oxidative burst (100%). The exposure of whole blood to PRBC supernatants + fMLP led to a 1.3-fold increase in neutrophil oxidative burst as compared with fMLP alone, indicating that PRBC supernatants prime neutrophils for oxidative burst by 75%. More importantly, PTX decreased neutrophil oxidative burst by 114% in supernatant + fMLP-stimulated whole blood (p < 0.001). PTX decreased CD11b expression in both fMLP (p < 0.01) and fMLP+supernatant-stimulated whole blood (p < 0.05). Supernatant from PRBCs did not have an additive effect to fMLP alone on CD11b expression. N-formyl-methionyl-leucyl-phenylalanine-induced CD35 expression was downregulated by PTX. The addition of PRBC supernatant did not increase the already upregulated fMLP-induced CD35 expression. CONCLUSIONS: Our results suggest that adding PTX to PRBC supernatant markedly decreases neutrophil activation. The lack of successful treatment strategies to effectively modulate the inflammatory response after blood transfusion indicates the need for novel therapies. Because the deleterious effects of blood transfusion on end-organ injury and MOF are associated with neutrophil activation, the adjunct use of PTX to blood transfusion may have therapeutic potential.

Blood Preservation↗
PubMed2005

Nonspecific phosphodiesterase inhibition attenuates liver injury in acute endotoxemia.

BACKGROUND: Endotoxemia is accompanied by pro-inflammatory cytokine production, generation of reactive oxygen species, and end-organ injury. Pentoxifylline (PTX), a methylxanthine derivative and phosphodiesterase inhibitor, is known for its anti-inflammatory properties, including down-regulation of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha synthesis. Its effects on liver function and hepatic histology following acute endotoxemia have not been investigated fully. We hypothesized that PTX would preserve liver architecture and function after intravenous lipopolysaccharide (LPS) injection. METHODS: Anesthetized Sprague-Dawley rats received an i.v. bolus injection of LPS (5 mg/kg), LPS + PTX (25 mg/kg), or saline (sham). Plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), TNF-alpha, IL-6, and nitrite were measured at different time points after LPS injection. Liver injury was graded according to a scoring system in a blinded fashion from 0 (normal) to 4 (severe) for hepatocellular necrosis, hemorrhage, and parenchymal and sinusoidal inflammatory infiltrates. Neutrophil infiltration was measured by counting myeloperoxidase (MPO)-positive stained cells. Nuclear factor (NF)-kappaB p-65 was measured by counting positive stained nuclei of hepatocytes and Kupffer cells (KC). Inducible nitric oxide synthase (iNOS) was evaluated by positively stained KC. Data are presented as mean +/- SEM. Analysis of variance with p < 0.05 was considered statistically significant. RESULTS: Animals treated with PTX showed a significant reduction in liver injury score and neutrophil infiltration. Treatment with PTX significantly decreased TNF-alpha, IL-6, and the concentrations of AST and ALT when compared to LPS alone. In addition, a significant decrease in NF-kappaB-positive staining in hepatocytes and KC, as well as in KC iNOS immunostaining was observed in PTX-treated animals compared to the LPS group. CONCLUSIONS: Pentoxifylline downregulates the inflammatory response significantly and decreases liver injury in acute endotoxemia.

Alanine Transaminase↗
PubMed2005

Long-term posttraumatic stress disorder persists after major trauma in adolescents: new data on risk factors and functional outcome.

BACKGROUND: Little is known about long-term psychological outcomes after major trauma in adolescents, a leading cause of death and preventable morbidity in this age group. A prospective epidemiologic study was conducted to examine quality of life (QoL) and posttraumatic stress disorder (PTSD) outcomes in injured adolescents. The specific objectives of the present report are to describe long-term PTSD and to identify risk factors for long-term PTSD and the impact of PTSD on QoL. METHODS: Between April 26, 1999, and November 13, 2002, 401 eligible trauma patients aged 12 to 19 years triaged to five participating trauma center hospitals in a regionalized trauma system were enrolled in the study. The admission criteria for patients were as follows: age 12 to 19 years and injury diagnoses excluding severe traumatic brain injury or spinal cord injury. PTSD was diagnosed with the Impact of Events Scale-Revised; scores of 24+ were used to diagnose PTSD. QoL after trauma was measured using the Quality of Well-Being scale, a sensitive and well-validated functional index (range: 0 = death to 1.000 = optimum functioning). Patient outcomes were assessed at discharge and at 3, 6, 12, 18, and 24 months after discharge. RESULTS: The rate of long-term PTSD was 27%, with high rates over the follow-up period. Risk factors for long-term PTSD were perceived threat to life (odds ratio [OR], 2.2; p < 0.001.); death of a family member at the scene (OR, 4.7; p < 0.001); no control over injury event (OR, 1.7; p < 0.05), and violence-related injury (OR, 2.2; p < 0.05). PTSD in adolescents was significantly and strongly associated with female gender, older age, low socioeconomic status, drug and alcohol abuse, and other adolescent behavioral problems. Long-term PTSD was also associated with marked and significant QoL deficits throughout the 24-month follow-up interval. CONCLUSION: High rates of long-term PTSD persist after major trauma in adolescents. Injury events such as perceived threat to life and control over the event are strongly associated with PTSD risk. Prolonged PTSD severely impacts QoL outcomes. Early identification and treatment of risk factors for long-term PTSD will be important to improve outcomes in injured adolescents.

Adolescent↗
PubMed2005

Role of hypertonic saline and pentoxifylline on neutrophil activation and tumor necrosis factor-alpha synthesis: a novel resuscitation strategy.

BACKGROUND: Hypertonic saline (HS) and pentoxifylline (PTX) have been shown to modulate polymorphonuclear neutrophil (PMN) functions after shock and sepsis. We hypothesized that a combination of HS and PTX (HSPTX) would down-regulate PMN functions and inflammatory mediator synthesis more effectively than each alone, possibly by acting at different steps of the signaling pathways, ultimately leading to an enhanced effect. METHODS: Whole blood from healthy volunteers was stimulated with lipopolysaccharide (LPS) (100 microg/mL), f-methionyl-leucyl-phenylalanine (1 micromol/L), and phorbol 12-myristate 13-acetate (1 microg/mL). Baseline oxidative burst was measured by flow cytometry. Two different concentrations of NaCl to achieve increases of 10 mmol/L (HS10) and 40 mmol/L (HS40) above isotonicity, simulating increases in sodium levels seen after infusion of 3% HS and 7.5% HS, were used. PTX (2 mmol/L), HS10, HS40, HSPTX10, and HSPTX40 were added to whole blood concomitantly to the activators. PMN CD14 and CD11b expression were measured by flow cytometry and tumor necrosis factor-alpha levels by enzyme-linked immunosorbent assay in LPS-stimulated whole blood. RESULTS: The combination of PTX with HS10 and with HS40 markedly decreased LPS- (27 +/- 7 and 23 +/- 6 vs. 100; p < 0.01), f-methionyl-leucyl-phenylalanine- (54 +/- 11 and 55 +/- 8 vs. 100; p < 0.05), and phorbol 12-myristate 13-acetate- (30 +/- 4 and 54 +/- 9 vs. 100; p < 0.01 and p < 0.05, respectively) induced PMN oxidative burst. Furthermore, a significant decrease in LPS-induced neutrophil CD11b expression after PTX treatment (79 +/- 5 vs. 100; p < 0.05) and HSPTX40 (68 +/- 7 vs. 100; p < 0.05) was observed. HSPTX10 (7 +/- 0.6; p < 0.001) or HSPTX40 (6 +/- 1.4; p < 0.001) markedly decreased tumor necrosis factor-alpha production to levels similar to those observed with PTX alone (6.5 +/- 0.5; p < 0.001) and significantly lower than HS10 (110 +/- 4.9; p < 0.001) and HS40 alone (83 +/- 1.5; p < 0.001) CONCLUSION: HSPTX down-regulates neutrophil activation and proinflammatory mediator synthesis more effectively that HS alone. HSPTX may have significant applications as a novel fluid resuscitation strategy in hemorrhagic shock.

CD11b Antigen↗
PubMed2005

Reversal of anticoagulation in trauma: a North-American survey on clinical practices among trauma surgeons.

BACKGROUND: Recent studies addressing reversal of anticoagulation in trauma have reported conflicting results. We hypothesized that current clinical practice is variable throughout North America. METHODS: We surveyed 100 trauma surgeons to obtain information regarding variability in current clinical practice. RESULTS: Seventy-five of 100 trauma surgeons surveyed responded, and the majority (98.7%) agreed that preinjury anticoagulation poses problems in trauma management that include bleeding, increased complications, and mortality. Nine participants (12.2%) had a protocol addressing reversal of anticoagulation in their institution. Most use fresh frozen plasma based on the type and location of injury, initial international normalized ratio (INR), and targeted INR value. Fresh frozen plasma was consistently used in patients with positive head computed tomographic scans, hemothorax, nonoperative solid organ injury management, pelvic and long bone fractures, and any operative intervention. Practice inconsistencies were found in patients with loss of consciousness and normal head computed tomographic scan, facial and rib fractures, and pulmonary contusion. Significant variability was found in the reversal INR target. One third of participants agreed that anticoagulation could be restarted 5 to 7 days after craniotomy; one sixth would do so within 72 hours and one third would wait 10 or more days. Most agreed that anticoagulation could be restarted 3 days after chest, abdominal, and orthopedic operations. Significant inconsistencies were also observed regarding when to restart anticoagulation in closed head injury patients treated nonoperatively. CONCLUSION: On the basis of the discrepancies observed in this survey, a clinical trial addressing specific injury location and patterns, INR thresholds, and type of strategy to achieve reversal is warranted, and most would agree to participate.

Abdominal Injuries↗
PubMed2005

Recovery at one year following isolated traumatic brain injury: a Western Trauma Association prospective multicenter trial.

BACKGROUND: Age has been shown to be a primary determinant of survival following isolated traumatic brain injury (TBI). We have previously reported that patients > or =65 years who survived mild TBI have decreased functional outcome at 6 months compared with younger patients. The purpose of this study was to further investigate the effect of age on outcome at 1 year in all patients surviving isolated TBI. METHODS: The Western Trauma Association multicenter prospective study included all patients sustaining isolated TBI defined as Abbreviated Injury Scale score for Head > or = 3 with an Abbreviated Injury Scale score in any other body area < or = 1. Outcome data included discharge disposition, Glasgow Outcome Scale score (1 = dead to 5= full recovery) and modified Functional Independence Measure (FIM) score measuring feeding, expression, and locomotion (1 = total dependence to 4 = total independence) for each component at discharge and 1 year. RESULTS: In all, 295 patients were enrolled with a follow-up of 82%, resulting in 241 study patients. An additional five patients died from non-TBI causes and were excluded. The mean and median times for the last follow-up in the 236 remaining patients were 307 and 357 days, respectively. Patients were divided into four age ranges: 18 to 29 years (n = 66), 30 to 44 years (n = 54), 45 to 59 years (n = 50), and > or =60 years (n = 65). More severe TBIs, as measured by admitting Glasgow Coma Scale (GCS), were observed in the youngest group compared with all others but there were no differences in mean GCS between the remaining three groups. There were no differences in neurosurgical intervention between the groups. Age was a major determinant in the outcome at discharge and last follow-up. Patients over 60 years discharged with a GOS < or =4 were less likely to improve at 1 year than all other groups (37% versus 63 to 85%; p < or = 0.05). Patients between 18 and 29 years of age had the lowest mean Glasgow Outcome Scale and discharge FIM scores, which correlated with the low admission GCS. Despite the increased severity of TBI, this group had the best FIM score at 1 year. In contrast, patients older than 60 years had the least improvement and had a significantly lower final FIM score at 1 year compared with all other groups. CONCLUSION: Older patients following isolated TBI have poorer functional status at discharge and make less improvement at 1 year compared with all other patients. These worse outcomes occur despite what appears to be less severe TBI as measured by a higher GCS upon admission. Differences in outcome begin to appear even in patients between 45 and 59 years. Further investigations with more detailed outcome instruments are required to better understand the qualitative limitations of a patient's recovery and to devise strategies to maximize functional improvement following TBI. Age is an exceedingly important parameter affecting recovery from isolated TBI.

Adolescent↗
PubMed2005

High rates of acute stress disorder impact quality-of-life outcomes in injured adolescents: mechanism and gender predict acute stress disorder risk.

BACKGROUND: Injury is the leading cause of death and functional disability in adolescent children. Little is known about quality of life and psychological outcomes after trauma in adolescents. The Trauma Recovery Project in Adolescents is a prospective epidemiologic study designed to examine multiple outcomes after major trauma in adolescents aged 12 to 19 years, including quality of life (QoL) and psychological sequelae such as acute stress disorder (ASD) and posttraumatic stress disorder (PTSD). The specific objectives of the present report are to examine ASD rates and the association of ASD with QoL outcomes in injured adolescents. METHODS: Between April 26, 1999, and November 13, 2002, 401 eligible trauma patients aged 12 to 19 years triaged to five participating trauma center hospitals in a regionalized trauma system were enrolled in the study. The admission criteria for patients were as follows: (1) age 12 to 19 years and (2) injury diagnoses excluding severe traumatic brain injury (TBI) or spinal cord injury. QoL after trauma was measured using the Quality of Well-being (QWB) scale, a sensitive and well-validated functional index (range, 0 = death to 1.000 = optimum functioning). ASD (before discharge) was diagnosed with the Impact of Events Scale-Revised. Scores of 24+ were used to diagnose ASD. Patient outcomes were assessed at discharge and at 3, 6, 12, 18, and 24 months after discharge. RESULTS: ASD before discharge was diagnosed in 40% of adolescent trauma survivors. ASD status was associated with large QoL deficits during follow-up, as follows: 3-month, ASD-positive QWB score = 0.667 vs. ASD-negative QWB score = 0.710, p < 0.01; 6-month, ASD-positive QWB score = 0.704 vs. ASD-negative QWB score = 0.742, p < 0.001; 12-month: ASD-positive QWB score = 0.718 vs. ASD-negative QWB score = 0.757, p < 0.01; 24-month, ASD-positive QWB score = 0.725 vs. ASD-negative QWB score = 0.769, p < 0.01. Female sex and violent mechanism predicted ASD risk (47% female vs. 36% male; odds ratio, 1.6; p < 0.05; violence 54% vs. 38%; odds ratio, 1.9; p < 0.01). CONCLUSIONS: Adolescent trauma survivors have high rates of ASD. ASD severely impacts QoL outcomes and is associated with female sex and mechanism of injury in adolescents. Early recognition and treatment of ASD in seriously injured adolescents will improve QoL outcomes.

Adolescent↗
PubMed2005

Phosphodiesterase inhibition decreases nuclear factor-kappaB activation and shifts the cytokine response toward anti-inflammatory activity in acute endotoxemia.

BACKGROUND: In sepsis, activation of inflammatory cells and excessive production of proinflammatory cytokines leads to tissue injury, multiple organ failure, and death. We postulated that attenuation but not complete abrogation of hyperinflammation is of clinical benefit in sepsis. Because pentoxifylline (PTX) is known to decrease tumor necrosis factor (TNF)-alpha production and to increase anti-inflammatory cytokine synthesis, we tested the hypothesis that PTX treatment would change the pro- and anti-inflammatory balance and decrease mortality in a murine model of acute endotoxemia. In addition, we investigated the effects of PTX on nuclear factor (NK)-kappaB activation using lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) as a model. METHODS: Sprague-Dawley rats were treated with intravenous saline (sham), LPS (lipopolysaccharide, Escherichia coli serotype 0111:B4, 5 mg/kg), and concomitant injection of LPS + PTX (25 mg/kg). Four- and 24-hour plasma TNF-alpha and interleukin (IL)-10 levels, 4-hour white cell count, and 24-hour mortality rates were assessed. The IL-10/TNF-alpha ratio was also calculated. Human PBMCs were stimulated with LPS (10 microg/mL) and exposed to PTX (20 mM) concomitantly or 15 minutes after LPS stimulation. I-kappaB phosphorylation by Western blot and NF-kappaB nuclear translocation by electrophoretic mobility shift assay were assessed. RESULTS: PTX markedly down-regulates TNF-alpha production. IL-10 levels at 4 hours were up-regulated in both LPS and PTX + LPS-treated animals; however, levels were higher in the LPS groups, which paralleled high TNF-alpha levels. In contrast, IL-10 levels at 4 and 24 hours in PTX + LPS-treated animals remained constant, whereas in LPS-treated animals, IL-10 levels at 24 hours were markedly decreased. A shift in the internal milieu balance toward anti-inflammatory activity was confirmed by the calculation of the IL-10/TNF-alpha ratio. These changes were not related to changes in the number of circulating leukocytes. The 24-hour mortality rate was 50% in the LPS group and nil in PTX-treated animals. In LPS-stimulated PBMCs, PTX markedly decreases I-kappaB phosphorylation and NF-kappaB nuclear translocation. CONCLUSION: PTX enhances anti-inflammatory activity and decreases mortality in acute endotoxemia. PTX may be an important adjunct to therapies aiming to modulate the inflammatory response in sepsis.

Analysis of Variance↗