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Biomedical subjects

P A Kearney

Publications and source records attributed to P A Kearney.

At least 19 recordsLinked to original sources

A multicenter evaluation of whether gender dimorphism affects survival after trauma.

BACKGROUND: The frequency of women who have sustained severe injuries has increased over the past 30 years. The purpose of this study was to evaluate whether severely injured women have a survival advantage over men. To address this issue, we undertook a multicenter evaluation of the effects of gender dimorphism on survival in trauma patients. METHODS: Patient information was collected from the databases of three level I trauma centers. We included all consecutive patients who were admitted to these centers over a 4-year period. We evaluated the effects of age, gender, mechanism of injury, pattern of injury, Abbreviated Injury Score (AIS), and Injury Severity Score (ISS) on survival. RESULTS: A total of 20,261 patients were admitted to the three trauma centers. Women who were younger than 50 years of age (mortality rate 5%) experienced a survival advantage over men (mortality rate 7%) of equal age (odds ratio 1.27, P <0.002). This advantage was most notably found in the more severely injured (ISS >25) group (mortality rate 28% in women versus 33% in men). This difference was not attributable to mechanism of injury, severity of injury, or pattern of injury. CONCLUSIONS: Severely injured women younger than 50 years of age have a survival advantage when compared with men of equal age and injury severity. Young men have a 27% greater chance of dying than women after trauma. We conclude that gender dimorphism affects the survival of patients after trauma.

Female↗

Enoxaparin treatment in high-risk trauma patients limits the utility of surveillance venous duplex scanning.

OBJECTIVE: The value of surveillance venous duplex scanning for detecting unsuspected deep venous thrombosis (DVT) in trauma patients who are receiving enoxaparin prophylaxis is open to question. This study was undertaken to determine whether enoxaparin reduced the clinical utility of surveillance scanning and whether management of these patients was altered by findings of the scans. METHODS: The medical records of trauma patients who met defined criteria for high DVT risk, admitted during 30 consecutive months, were reviewed. These patients received enoxaparin 30 mg every 12 hours for the duration of their admissions. Per protocol, surveillance lower extremity venous duplex scans were performed within 72 hours of enoxaparin administration and then weekly until patients were discharged from the hospital. The records were reviewed for thromboembolic events (DVT or pulmonary embolism [PE]), patient location and ambulatory status, therapeutic interventions (systemic anticoagulation, vena cava filter), and complications of enoxaparin therapy. RESULTS: A total 241 patients underwent 513 venous duplex examinations (1-13 per patient). Eight patients had DVT on the initial scan; seven of these patients were asymptomatic. Five were treated with anticoagulation and/or vena cava filter placement. Of the 233 patients with initially negative duplex scan results, five patients (2%) developed clinically unsuspected lower extremity DVT while hospitalized. All of these five patients were in an intensive care unit. Three of the five patients had no change in treatment. Two of the five underwent anticoagulation, and one vena cava filter was placed. PE occurred in two hospitalized patients, one of whom was ambulatory, with negative duplex scan results. After hospital discharge, six other patients had symptomatic DVT or PE despite in-hospital scans with negative results. Complications associated with enoxaparin included hemorrhage (2) and thrombocytopenia (8). CONCLUSIONS: After initial negative scan results, repeat surveillance duplex scanning during hospitalization detected a low incidence (2%) of DVT in high-risk patients. Furthermore, the detection of unsuspected DVT altered the clinical management of less than 1% of the patients tested. Thus, after a venous duplex scan with negative results and initiation of enoxaparin prophylaxis, subsequent surveillance duplex examinations are not warranted in asymptomatic trauma patients.

Adolescent↗

Arginase I expression and activity in human mononuclear cells after injury.

OBJECTIVE: To determine the effect of trauma on arginase, an arginine-metabolizing enzyme, in cells of the immune system in humans. SUMMARY BACKGROUND DATA: Arginase, classically considered an enzyme exclusive to the liver, is now known to exist in cells of the immune system. Arginase expression is induced in these cells by cytokines interleukin (IL) 4, IL-10, and transforming growth factor beta, corresponding to a T-helper 2 cytokine profile. In contrast, nitric oxide synthase expression is induced by IL-1, tumor necrosis factor, and gamma interferon, a T-helper 1 cytokine profile. Trauma is associated with a decrease in the production of nitric oxide metabolites and a state of immunosuppression characterized by an increase in the production of IL-4, IL-10, and transforming growth factor beta. This study tests the hypothesis that trauma increases arginase activity and expression in cells of the immune system. METHODS: Seventeen severely traumatized patients were prospectively followed up in the intensive care unit for 7 days. Twenty volunteers served as controls. Peripheral mononuclear cells were isolated and assayed for arginase activity and expression, and plasma was collected for evaluation of levels of arginine, citrulline, ornithine, nitrogen oxides, and IL-10. RESULTS: Markedly increased mononuclear cell arginase activity was observed early after trauma and persisted throughout the intensive care unit stay. Increased arginase activity corresponded with increased arginase I expression. Increased arginase activity coincided with decreased plasma arginine concentration. Plasma arginine and citrulline levels were decreased throughout the study period. Ornithine levels decreased early after injury but recovered by postinjury day 3. Increased arginase activity correlated with the severity of trauma, early alterations in lactate level, and increased levels of circulating IL-10. Increased arginase activity was associated with an increase in length of stay. Plasma nitric oxide metabolites were decreased during this same period. CONCLUSIONS: Markedly altered arginase expression and activity in cells of the human immune system after trauma have not been reported previously. Increased mononuclear cell arginase may partially explain the benefit of arginine supplementation for trauma patients. Arginase, rather than nitric oxide synthase, appears to be the dominant route for arginine metabolism in immune cells after trauma.

Adult↗

The routine use of sonography in penetrating torso injury is beneficial.

BACKGROUND: Torso sonography (focused assessment with sonography for trauma [FAST]) has been added to our protocols for the evaluation of penetrating torso injury. The purpose of this study was to evaluate our recent experience and determine whether the use of FAST is beneficial. METHODS: From January 1999 to January 2000, patients with penetrating torso injury and no clinical indication for surgery were evaluated by sonography with a selective use of other investigations. FAST consisted of sonographic views of the peritoneum and/or pericardium to determine the presence or absence of fluid. RESULTS: During the study period, there were 238 victims of penetrating injury assessed by our trauma service, and sonography was performed in 72 (30%) patients as per our protocols. There were 31 stab, 37 gunshot/shotgun and, and 4 puncture wounds. Thirty-eight patients had peritoneal views, 6 patients had pericardial views, and 28 patients had both pericardial and peritoneal views obtained. Thirteen of 66 patients had free fluid in the peritoneal cavity and 12 of the 13 patients had a therapeutic laparotomy. No peritoneal fluid was seen in 53 of 66 patients, of whom 6 had abdominal injuries, 5 requiring surgery for diaphragm or bowel injuries. The sensitivity of FAST alone for abdominal injury was 67%, specificity was 98%, positive predictive value was 92%, and negative predictive value was 89%. Pericardial fluid was seen in 3 of 34 patients; one had a heart wound and two had negative pericardial windows. All 31 patients without pericardial fluid recovered without surgery. CONCLUSION: The routine use of sonography in penetrating torso injury is beneficial. The detection of pericardial or peritoneal fluid is clinically useful. However, a negative FAST examination does not exclude abdominal injury, such as a diaphragm or hollow viscus wound, and further investigation or close follow-up is required.

Abdominal Injuries↗

Surgery induces human mononuclear cell arginase I expression.

BACKGROUND: Arginase is a metabolic enzyme for the amino acid arginine that participates in the immune response to trauma. We hypothesize that surgical trauma induces arginase expression and activity in the human immune system. METHODS: Peripheral mononuclear cell (MNC) arginase activity and expression and plasma nitric oxide metabolites and interleukin (IL)-10 were measured in patients undergoing elective general surgery. Twenty-two healthy volunteers served as a comparison population. RESULTS: MNC arginase activity increased within 6 hours of surgery (p < 0.05) and coincided with increased arginase I protein expression. Plasma nitric oxide metabolites decreased significantly postoperatively (p < 0.05). Patients lacking an elevation in IL-10 failed to demonstrate increased MNC arginase activity. CONCLUSION: Increased MNC arginase expression may contribute to postsurgical immune dysfunction by affecting arginine use and availability and nitric oxide metabolism in the immune system. Plasma IL-10 may play a role in regulating MNC arginase activity.

Adult↗

Alterations in arginine metabolic enzymes in trauma.

Arginine is the sole substrate for nitric oxide (NO) synthesis by NO synthases (NOS) and promotes the proliferation and maturation of human T-cells. Arginine is also metabolized by the enzyme arginase, producing urea and ornithine, the precursor for polyamine production. We sought to determine the molecular mechanisms regulating arginase and NOS in splenic immune cells after trauma. C3H/HeN mice underwent laparotomy as simulated moderate trauma or anesthesia alone (n = 24 per group). Six, 12, 24, or 48 h later, 6 animals from each group were sacrificed, and splenectomy was performed and plasma collected. Six separate animals had neither surgery nor anesthesia and were sacrificed to provide resting values (t = 0 h). Spleen arginase I and II and iNOS mRNA abundance, arginase I protein expression, and arginase activity were determined. Plasma NO metabolites (nitrite + nitrate) were also measured. Trauma increased spleen arginase I protein expression and activity (P = 0.01) within 12 and for at least 48 h after injury and coincided with up-regulated arginase I mRNA abundance at 24 h. Neither arginase II nor iNOS mRNA abundance in the spleen was significantly increased by trauma at 24 h. Plasma nitrite + nitrate was decreased in animals 48 h post-injury compared to anesthesia controls (P < 0.05). Trauma induces up-regulation of arginase I gene expression in splenic immune cells within 24 h of injury. Arginase II is not significantly up-regulated at that time point. Arginase I, rather than iNOS appears to be the dominant route for arginine metabolism in splenic immune cells 24 h after trauma.

Animals↗

Beta adrenoceptor regulation of macrophage arginase activity.

BACKGROUND: Arginase, which metabolizes L-arginine within the urea cycle, is essential for production of polyamines and affects production of nitric oxide by depletion of L-arginine, the common substrate for both arginase and nitric oxide synthase. Having shown that trauma increases splenic macrophage arginase activity, we seek to define the mechanisms for this. RAW macrophage arginase activity and expression are increased by 8-bromo-cAMP in vitro. We hypothesize that since catecholamines increase cAMP, trauma-induced splenic arginase activity may be mediated by post-injury catecholamine release. METHODS: RAW 264.7 macrophage arginase activity was measured in vitro in response to 4 catecholamines with or without propranolol or lipopolysaccharide (LPS). C57BL/6 mice underwent laparotomy as a model of moderate trauma after propranolol treatment, with and without intraperitoneal Escherichia coli LPS administration as a simulated pro-inflammatory stimulus. RESULTS: Macrophage arginase activity increased in vitro in response to catecholamines or LPS (P < .05). Propranolol pretreatment blocked macrophage arginase activity induced by epinephrine (10 mumol/L) in vitro (P < .05). Trauma or LPS alone increased splenic arginase activity in vivo (P < .05). Propranolol did not alter LPS-induced splenic arginase activity but did significantly reduce trauma-induced splenic arginase activity (P < .05). CONCLUSIONS: Catecholamines alone increase macrophage arginase activity through beta-adrenoceptor activation. Increased splenic arginase activity induced by moderate trauma is decreased by beta-adrenoceptor blockade, suggesting that trauma-induced arginase activity is partly mediated by endogenous catecholamines.

8-Bromo Cyclic Adenosine Monophosphate↗

Trauma increases extrahepatic arginase activity.

BACKGROUND: Although expressed primarily in the liver, arginase activity also is present in extrahepatic tissues and specifically in macrophages, where it may play diverse physiologic roles in wound healing, cellular proliferation, and the regulation of nitric oxide production. Arginase activity in immune cells is upregulated by certain cytokines such as IL-4, IL-10, and TGF-beta and by catecholamines. Since the release of these substances is increased after trauma, we hypothesized that arginase activity would also be increased in immune cells after trauma. The current work tests this hypothesis. METHODS: A model of surgical trauma was created in C3H/HeN mice by performing an exploratory laparotomy. Tissue arginase activity and arginase I protein expression were determined. As a control, arginase activity and expression were also stimulated with the use of endotoxin. In addition, we evaluated the expression of inducible nitric oxide synthase and the accumulation of nitric oxide metabolites in plasma. RESULTS: Surgical trauma was associated with a significant increase in arginase activity in splenic and renal tissues (P < .05). Splenic macrophages from trauma animals exhibited arginase activity levels approximately 10 times those of controls (P < .05). Endotoxin alone increased arginase activity in the spleen, but this increase was less than that of trauma alone (P < .05). Arginase activity remained elevated after trauma for up to 4 days and normalized by day 7. Arginase I expression was upregulated by trauma in both splenic and renal tissue and by endotoxin in the spleen only. Despite upregulation of inducible nitric oxide synthase in trauma animals, circulating nitric oxide metabolites were decreased 2 days after trauma compared with controls (P < .05). Endotoxin-induced nitric oxide metabolites were also reduced in trauma animals compared with endotoxin treatment alone (P < .05), but this normalized by day 4. CONCLUSIONS: Extrahepatic arginase expression and activity is increased after trauma and may provide the necessary precursors for cellular proliferation and repair or may play a regulatory role in the production of nitric oxide.

Animals↗

A single-center 8-year experience with percutaneous dilational tracheostomy.

OBJECTIVE: To determine surgical, postoperative, and postdischarge complications associated with percutaneous dilational tracheostomy (PDT) in an 8-year experience at the University of Kentucky. SUMMARY BACKGROUND DATA: There are known risks associated with the transport of critically ill patients to the operating room for elective tracheostomy, and less-than-optimal conditions may interfere with open bedside tracheostomy. PDT has been introduced as an alternative to open tracheostomy. Despite information supporting its safety and utility, the technique has been criticized because advocates had not provided sufficient information regarding complications. METHODS: A prospective database was initiated on all patients who underwent PDT between September 1990 and May 1998. The database provided indication, procedure time, duration of intubation before PDT, and intraoperative and postoperative complications. Retrospective review of medical records and phone interviews provided long-term follow-up information. RESULTS: In the 8-year period, 827 PDTs were performed in 824 patients. Two patients were excluded because PDT could not be completed for technical reasons. There were 519 male and 305 female patients. Mean age was 56 years. Prolonged mechanical ventilatory support was the most common indication. Mean procedure time was 15 minutes, and the average duration of intubation before PDT was 10 days. The intraoperative complication rate was 6%, with premature extubation the most common complication. The procedure-related death rate was 0.6%. Postoperative complications were found in 5%, with bleeding the most common. With a mean follow-up of greater than 1 year, the tracheal stenosis rate was 1.6%. CONCLUSIONS: On the basis of this large, single-center study, the authors conclude that when performed by experienced surgeons, PDT is a safe and effective alternative to open surgical tracheostomy for intubated patients who require elective tracheostomy.

Databases, Factual↗

Utilization of FAST (Focused Assessment with Sonography for Trauma) in 1999: results of a survey of North American trauma centers.

Although much has been written about FAST (Focused Assessment with Sonography for Trauma) in the last decade little is known about its present clinical utilization. The purpose of this study was to evaluate and characterize the contemporary utilization of FAST at trauma centers in the United States and Canada. In 1999 trauma directors or their delegates at Level I regional trauma centers in the United States and Canada were surveyed either by fax or phone regarding the present utilization and the future of FAST at their center. The overall survey response rate was 91 per cent with 96 of 105 centers completing the survey. Of the 96 centers surveyed 78 were in the United States and 18 were in Canada. Of the 78 U.S. centers surveyed 62 (79%) routinely use FAST, and it is done by surgeons in 39 per cent, surgeons and emergency departments in 21 per cent, emergency departments in 5 per cent, and radiologists in 35 per cent. Most centers (79%) thought that it sped up their workups, and 89 per cent said it was an advance in patient care. FAST is used in penetrating injury at 58 per cent of centers, and some centers use FAST to assess organ injury. The utilization of diagnostic peritoneal lavage and CT has markedly decreased at many centers. Almost all respondents thought that FAST should be a component of surgery resident training. The utilization of FAST is significantly less in Canada than in the United States (P < 0.05). Our conclusions are the following. FAST has become routinely used at the majority of the U.S. centers surveyed. FAST is performed by clinicians at 65 per cent of the trauma centers surveyed. The utilization of CT and diagnostic peritoneal lavage has changed. Many centers have broadened the scope of FAST to include the assessment of organ, pediatric, and penetrating injury.

Abdominal Injuries↗

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.

Adolescent↗

Penetrating injuries of the neck: selective management evolving.

Since 1990, a selective management algorithm has been used in our Trauma Center to treat 91 patients with penetrating neck injuries. Group A (n = 37) sustained zone I, zone III, or multiple-zone injuries; Group B (n = 54) sustained zone II injuries [most (55, 66.4%) from gunshot or shotgun wounds]. Nineteen Group A and 21 Group B patients required mandatory neck exploration. Vascular or aerodigestive tract injuries were found and adequately repaired in 15 Group A and 11 Group B patients. The superficial wounds of three Group A and seven Group B patients were closed, and the patients were observed for 24 hours. The remaining 15 Group A and 24 Group B patients underwent routine angiogram, arbitrary barium swallow, and, if necessary, esophagoscopy. Two of these Group B patients required surgery for common carotid artery injuries. One patient died 4 months later because of missed vertebral artery pseudoaneurysm. Overall mortality and complication rates were 6 and 1 per cent. Unnecessary exploration was avoided in 52 per cent of cases regardless of the location of the wound. Mortality and morbidity rates were acceptable. Patients with penetrating neck injuries could be safely managed selectively regardless of the injury zone.

Algorithms↗

Percutaneous dilational tracheostomy: report of 356 cases.

OBJECTIVE: To evaluate the procedure time, complications, and percutaneous dilational tracheostomy (PDT) charges. DESIGN: Operative data were prospectively collected for 356 PDTs including the initial series of 141 PDTs reported in 1994. Short- and long-term complications were retrospectively identified by review of medical records and patient telephone interviews. MATERIALS AND METHODS: PDT was performed using the "Ciaglia" method of serial dilation over a Seldinger guidewire. Discharged patients (n = 258) were followed for a mean (+/-SD) of 10 +/- 7 months. MEASUREMENTS AND MAIN RESULTS: The mean procedure time was 15 +/- 8 minutes; operative mortality rate, 0.3% (1/356); overall complication rate, 19% (69/356); long-term symptomatic tracheal stenosis rate, 3.7% (8/214). The mean total patient charge for bedside PDT was $1,370; for open tracheostomy in the operating room, $2,675. CONCLUSIONS: Surgeons can rapidly perform PDT at the bedside with a lower risk of complications than open tracheostomy and at a significantly reduced patient charge.

Adolescent↗

Transesophageal echocardiography in the diagnosis of traumatic rupture of the aorta.

BACKGROUND: Rupture of the aorta is a major cause of death after motor vehicle accidents. Survival depends on early diagnosis, and emergency aortography is the standard imaging method. Although transesophageal echocardiography is noninvasive and can provide high-resolution images of the aorta, information about its value in patients with trauma is limited. We conducted this study to assess prospectively the value of transesophageal echocardiography in the emergency evaluation of patients at risk for aortic injury. METHODS: Transesophageal echocardiography of the aorta was attempted in 101 patients admitted to the emergency room with a diagnosis of possible traumatic rupture of the aorta. Echocardiography and aortography personnel were notified simultaneously of the arrival of the patient, and the two tests were performed sequentially by operators who were blinded to the results of the other test. The sensitivity and specificity of transesophageal echocardiography were calculated on the basis of the results of aortography of the arch, surgery, or autopsy. RESULTS: Transesophageal echocardiography was attempted in 101 patients. The study was successfully performed in 93 patients but could not be completed in 8 because of lack of cooperation on the part of the patient (7 patients) or maxillofacial trauma (1 patient). Despite a high injury-severity score (mean, 29.6), transesophageal echocardiography was performed without complications, and within a mean (+/- SD) of 29 +/- 12 minutes. Eleven of the 93 studies (12 percent) demonstrated rupture of the aorta near the isthmus. The findings were confirmed in 10 of the 11 patients by aortography (9 patients), surgery (9 patients), or autopsy (1 patient), yielding a sensitivity of 100 percent and specificity of 98 percent for the detection of injury to the aorta. There was one false positive echocardiogram. CONCLUSIONS: Transesophageal echocardiography is a highly sensitive and specific method of detecting injury to the thoracic aorta. This technique can be used safely and quickly in critically injured patients with suspected traumatic rupture of the aorta and compares favorably with arch aortography.

Acute Disease↗

Echocardiography in the evaluation of thoracic trauma.

Echocardiography has become a useful diagnostic modality in the evaluation of cardiovascular injury after thoracic trauma. Valuable information about cardiac wall motion, valvular function, pericardial effusions, and ventricular volume status can be obtained without significant risk. More recent application for the diagnosis of traumatic aortic disruption provides a safer, easier, less expensive, and more accurate method for detecting these injuries. Cardiac evaluation with TTE is unsuccessful in approximately 20% of examinations and is unable to provide the image resolution of the more invasive transesophageal approach.

Aorta, Thoracic↗

Biliary sludging in critically ill trauma patients.

We used serial weekly ultrasonography to prospectively screen 19 critically ill trauma victims for the development of biliary sludge. Fourteen patients had sludge formation during their hospitalization. Sludge development was positively associated with increased transfusion requirements, but not with any other laboratory or clinical findings, including injury severity scores. The enteral feedings administered to most patients did not prevent sludge formation in the majority of cases; all five patients receiving total parenteral nutrition had sludge. Three patients had complications that could possibly be attributed to the sludge (one case of acalculous cholecystitis and two cases of mild pancreatitis). No such problems occurred in the five patients who did not have sludge. No long-term clinical problems related to sludge have occurred. We conclude that gallbladder sludge frequently develops in critically ill trauma patients and that sludge may be associated with pancreatobiliary complications.

Adolescent↗