Eicosapentaenoic acid and gamma-linolenic acid induce apoptosis in HL-60 cells.

Enteral nutrition with eicosapentaenoic acid (EPA; 20:5 n-3) and gamma-linolenic acid (GLA; 18:3 n-6) decreased pulmonary inflammation by reducing neutrophil counts and chemotactic factors in bronchoalveolar lavage fluid during acute respiratory distress syndrome (ARDS). We hypothesize that the anti-inflammatory effects of EPA and GLA may be due, in part, to induction of neutrophil apoptosis. The purpose of this study was to determine whether EPA and GLA, alone or in combination, trigger apoptotic cell death in the human promyelocytic leukemia HL-60 cell line. HL-60 cells were incubated with 10, 20, 50, and 100 micromol/L EPA, GLA, or various combinations of EPA and GLA for 2, 4, 8, 12, and 24 hs. Oleic acid (18:1 n-9) was used as a fatty acid control. Flow cytometry using dual staining with propidium iodide and annexin V-FITC assessed apoptosis, necrosis, and viability. Apoptosis was verified by DNA fragmentation as assessed by agarose gel electrophoresis. EPA, GLA, and various combinations of EPA and GLA significantly induced apoptosis and reduced cell viability in HL-60 cells. Viability was significantly reduced to the same extent with the combination of 50 micromol/L EPA\20 micromol/L GLA compared with 100 micromol/L EPA. These data indicate that EPA and GLA, alone or in combination, reduce cell survival by induction of apoptosis. Thus, induction of apoptosis by select dietary n-3 (EPA) and n-6 (GLA) polyunsaturated fatty acids may be the mechanism of the resolution of pulmonary inflammation in ARDS.

Contribution of age and gender to outcome of blunt splenic injury in adults: multicenter study of the eastern association for the surgery of trauma.

BACKGROUND: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. METHODS: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. RESULTS: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients > or = 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients > or = 55 was significantly greater than patients < 55 (43% vs. 23%). Patients > or = 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women > or = 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). CONCLUSION: Patients > or = 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women > or = 55 had significantly greater mortality and failure of NOM than women < 55.

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Blunt splenic injury in adults: Multi-institutional Study of the Eastern Association for the Surgery of Trauma.

BACKGROUND: Nonoperative management of blunt injury to the spleen in adults has been applied with increasing frequency. However, the criteria for nonoperative management are controversial. The purpose of this multi-institutional study was to determine which factors predict successful observation of blunt splenic injury in adults. METHODS: A total of 1,488 adults (>15 years of age) with blunt splenic injury from 27 trauma centers in 1997 were studied through the Multi-institutional Trials Committee of the Eastern Association for the Surgery of Trauma. Statistical analysis was performed with analysis of variance and extended chi2 test. Data are expressed as mean +/- SD; a value of p < 0.05 was considered significant. RESULTS: A total of 38.5 % of patients went directly to the operating room (group I); 61.5% of patients were admitted with planned nonoperative management. Of the patients admitted with planned observation, 10.8% failed and required laparotomy; 82.1% of patients with an Injury Severity Score (ISS) < 15 and 46.6% of patients with ISS > 15 were successfully observed. Frequency of immediate operation correlated with American Association for the Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III (38.1%), IV (73.7%), and V (94.9%) (p < 0.05). Of patients initially managed nonoperatively, the failure rate increased significantly by AAST grade of splenic injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p < 0.05). A total of 60.9% of the patients failed nonoperative management within 24 hours of admission; 8% failed 9 days or later after injury. Laparotomy was ultimately performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum. CONCLUSION: In this multicenter study, 38.5% of adults with blunt splenic injury went directly to laparotomy. Ultimately, 54.8% of patients were successfully managed nonoperatively; the failure rate of planned observation was 10.8%, with 60.9% of failures occurring in the first 24 hours. Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum.

Acute injuries of the trachea and major bronchi: importance of early diagnosis.

BACKGROUND: Tracheobronchial injuries are encountered with increasing frequency because of improvements in prehospital care and early initiation of the Advanced Trauma Life Support protocol. We review our experience with these injuries with the hypothesis that the leading determinant of patient outcome is the time interval to diagnosis. METHODS: Patients with tracheobronchial injury were identified from the registry of our level 1 trauma center during a 10-year period ending December 1997. Clinical presentation, diagnostic evaluation, surgical management, and outcome were reviewed. RESULTS: Twenty patients with ten cervical tracheal injuries and ten intrathoracic tracheobronchial injuries were treated. The mechanism of injury involved blunt trauma in 11 and penetrating trauma in 9. All patients underwent surgical debridement and primary repair. Patients with isolated airway injuries were discharged home after a mean hospital stay of 6 days and had no early complications. Three patients had delayed diagnosis (> 24 hours), and all sustained complications including death (1 patient) and multiorgan system failure (2 patients). The overall mortality rate was 15%. CONCLUSIONS: Operative management of tracheobronchial injuries can be achieved with acceptable mortality. Independent of mechanism or anatomic location of injury, delay in diagnosis is the single most important factor influencing outcome. Early recognition of tracheobronchial injury and expedient institution of appropriate surgical intervention are essential in these potentially lethal injuries.

Contrasting post-traumatic serial changes for D-dimer and PAI-1 in critically injured patients.

We measured D-dimer and plasminogen activator inhibitor-1 (PAI-1) activity in 45 trauma patients to assess their efficacy in predicting the post-traumatic hemostatic perturbations. We found the correlation between D-dimer measured by Simpli Red test and ELISA to be highly significant (p=0.0001). The D-dimer ELISA indicated that the serial changes of D-dimer after trauma were variable. However, the increases of D-dimer were associated with clinical conditions of the patient, such as trauma surgery, infections, or thrombotic complications. A significant correlation was found for D-dimer levels measured by ELISA versus the injury severity score (ISS) in all the trauma patients on day 1 (p=0.0153) and on day 2 (p=0.0495). The PAI-1 activity was increased at admission and showed a progessive decline from day 2 onward, and the correlation for the daily decline of PAI-1 was highly significant (p=0.0001). The PAI-1 activity and plasminogen activator activity showed a significant negative correlation on days 1, 2, and 3. PAI-1 activity correlated moderately with D-dimer level only on day 1 (p=0.0569). Three out of forty-five patients developed thrombotic complications: one patient who died from pulmonary embolism and two patients who developed adult respiratory distress syndrome (ARDS). In summary: 1) PAI-1 activity and D-dimer exhibited contrasting serial changes after trauma. 2) There was also a negative correlation between PAI-1 activity and PA activity. 3) A significant correlation of D-dimer with ISS confirms, as might be anticipated, that there is increased activation of the coagulation mechanism in severe injury, and suggests that D-dimer levels may prove useful to screen for patients at strong risks of thrombotic complications.

Prospective study of blunt aortic injury: Multicenter Trial of the American Association for the Surgery of Trauma.

BACKGROUND: Blunt aortic injury is a major cause of death from blunt trauma. Evolution of diagnostic techniques and methods of operative repair have altered the management and posed new questions in recent years. METHODS: This study was a prospectively conducted multi-center trial involving 50 trauma centers in North America under the direction of the Multi-institutional Trial Committee of the American Association for the Surgery of Trauma. RESULTS: There were 274 blunt aortic injury cases studied over 2.5 years, of which 81% were caused by automobile crashes. Chest computed tomography and transesophageal echocardiography were applied in 88 and 30 cases, respectively, and were 75 and 80% diagnostic, respectively. Two hundred seven stable patients underwent planned thoracotomy and repair. Clamp and sew technique was used in 73 (35%) and bypass techniques in 134 (65%). Overall mortality was 31%, with 63% of deaths being attributable to aortic rupture; mortality was not affected by method of repair. Paraplegia occurred postoperatively in 8.7%. Logistic regression analysis demonstrated clamp and sew (p = 0.002) and aortic cross clamp time of > or = 30 minutes (p = 0.01) to be associated with development of postoperative paraplegia. CONCLUSIONS: Rupture after hospital admission remains a major problem. Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard. Aortic cross clamp time beyond 30 minutes was associated with paraplegia; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach.

The effect of LPS on cytokine synthesis and lung neutrophil influx after hepatic ischemia/reperfusion injury in the rat.

OBJECTIVE: To determine if cytokine responses and lung injury induced by intravenous (i.v.) lipopolysaccharide (LPS) at 4 hr were enhanced in rats that had been previously subjected to 30 min of total liver ischemia (Pringle's maneuver) followed by 24 hr or 3 days of reperfusion. BACKGROUND: Many patients with liver trauma require occlusion of hepatic blood flow to control hemorrhage and facilitate repair. A significant number of these patients subsequently develop the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MOD) characterized by the release of cytokines and tissue neutrophil influx. Macrophages, including Kupffer cells, may be activated by ischemic injury and dysregulation of their response to LPS may contribute to the development of SIRS and acute respiratory distress syndrome. METHODS: Adult male Sprague-Dawley rats were randomly divided into six groups: three groups received total hepatic ischemia for 30 min and three groups had a sham procedure. Twenty-four hours or 3 days after hepatic ischemia/reperfusion injury, rats were treated with LPS (5 mg/kg) or saline and monitored for 4 hr. We collected serum, bronchoalveolar lavage (BAL) fluid, and lung tissue. RESULTS: Serum and BAL cytokine concentrations were significantly increased by i.v. LPS; however, hepatic ischemia/reperfusion injury 24 hr or 3 days before iv LPS ameliorated this cytokine response. The LPS-induced pulmonary neutrophil influx and histopathological changes were similar in sham and hepatic ischemia/reperfusion-injured groups. CONCLUSIONS: Hepatic ischemia/reperfusion injury significantly attenuated the serum and BAL cytokine concentrations, but did not change pulmonary neutrophil influx or histopathological alterations in response to i.v. LPS.

Intrahepatic absorbable fine mesh packing of hepatic injuries: preliminary clinical report.

A previous report from the authors' institution reported the effectiveness of hepatic packing with absorbable fine mesh (AFMP) for the control of hemorrhage in an animal model with an otherwise lethal hepatic injury. The technique has subsequently been applied to 12 abdominal trauma patients with hemodynamic instability and actively hemorrhaging hepatic injuries. Two patients expired in the operating room owing to uncontrolled hemorrhage from hepatic and associated injuries for a mortality of 16.7%. AFMP was successful in controlling hemorrhage in the remaining 10 patients. Hepatic injuries ranged from grade II to grade V, and all were actively hemorrhaging at the time of exploration. None of the surviving 10 patients experienced early or late recurrent bleeding attributable to the hepatic injuries, and there were no intraabdominal abscesses or late deaths. Liver function studies returned to normal prior to discharge in all surviving patients. Follow-up included serial computed tomographic scans, which demonstrated fibrosis incorporating the mesh packing. Complete resolution of injury and mesh appears to proceed over approximately a 6-month period. AFMP is a safe, effective method for controlling hepatic hemorrhage. It is easy to perform in the operating room, offers an excellent matrix for hemostasis, provides tamponade of bleeding sites, and does not require reoperation for removal of packing material, as is necessary with conventional, nonabsorbable packing techniques.

A prospective evaluation of thoracoscopy for the diagnosis of penetrating thoracoabdominal trauma.

Penetrating thoracoabdominal trauma presents a difficult diagnostic dilemma. Violation of the diaphragm may be very difficult to establish. Conventional diagnostic procedures such as chest radiography, computed tomography, and diagnostic peritoneal lavage have been shown to be unreliable. Mandatory exploratory celiotomy carries a 20%-30% negative rate. Twenty-eight patients with penetrating thoracoabdominal trauma over a 6-month period were prospectively evaluated by thoracoscopy at a major urban trauma center. All patients were hemodynamically stable, had no indications for immediate celiotomy, and demonstrated thoracic injury on chest radiography or physical examination. All thoracoscopy was performed in the operating room under general anesthesia. Patients consisted of 25 males and 3 females with an age range of 15-48 years. Mechanism of injury consisted of 24 stab wounds and 4 gunshot wounds. Twelve of the procedures were for right chest wounds and 16 involved the left hemithorax. Diaphragmatic injury was identified at thoracoscopy in 9 patients (32%), with all confirmed and repaired at celiotomy. Eight of 9 patients (89%) undergoing celiotomy were found to have significant intra-abdominal injuries requiring surgical repair. Thoracoscopy was also useful for evacuation of blood from the pleural space. There were no procedure-related complications. Thoracoscopy is a safe, accurate, reliable diagnostic technique for evaluating thoracoabdominal penetrating trauma. It is less invasive than celiotomy and has the added benefit of diagnosis and therapy of the intrathoracic injuries.

Total hepatic mesh wrap for hemostasis.

To improve hemostasis and avoid the complications of perihepatic packing, a technique of hepatic tamponade using total mesh wrap is reported. The method is geometrically, technically and mechanically feasible and appears to be effective in controlling severe parenchymatous bleeding.