Life-threatening dog attacks: a devastating combination of penetrating and blunt injuries.

BACKGROUND/PURPOSE: Children often are the victims of dog attacks. Although bite injuries sustained in an attack characteristically are attributed to the penetrating component of the bite, the blunt nature of a bite may represent the most serious and devastating component of injury. The purpose of this study was to characterize a group of children suffering life-threatening dog bites and examine the predominant aspect of injury. METHODS: Thirty-nine children were admitted to the trauma service at a regional pediatric trauma center with the diagnosis of dog bite injury over a 6-year period (1994 through 1999). Patient demographics, site and description of injury, and surgical procedures performed were recorded from a chart review. RESULTS: Mean age of the 35 children included for analysis was 5.4 years (range, 0.8 to 17 years). Twenty-five (71%) injuries occurred in the head and neck region. Eight (23%) children sustained life-threatening injuries. Of these, blunt force was the predominant injury in 6. This resulted in 1 (20%) arterial occlusion requiring vascular reconstruction, 2 (40%) permanent neurologic injuries (stroke, spinal cord transection), and 1 (20%) death (exsanguination). CONCLUSIONS: On evaluation of a dog attack, the focus generally is on the obvious penetrating aspect of the bite. Yet, we found the blunt component of injury can have devastating consequences reflected in acute arterial, brain, and spinal cord injury. Even in the absence of significant penetrating trauma, further evaluation should be considered to exclude occult blunt arterial or neurologic injury.

Thoracoscopic resection of mediastinal masses in infants and children: an evaluation of technique and results.

BACKGROUND: Thoracoscopy has been accepted as a technique in pediatric surgery for diagnosis of thoracic pathology, but there has been little experience using it as a therapeutic modality as well. The purpose of this report is to describe and critically evaluate a 7-year experience with thoracoscopic diagnosis and resection of mediastinal masses in infants and children. METHODS: From February 1993 to June 2000, 39 patients presented with mediastinal masses and no tissue diagnosis. Age ranged from 5 months to 18 years old and weight from 3.6 to 110 kg. Twelve children had anterior mediastinal masses, 27 posterior. The patients were positioned in a modified prone or supine position, and single lung ventilation was performed on the contralateral side. Three or 4 valved trocars were utilized with 3 and 5 mm instrumentation. RESULTS: A total of 38 of 39 procedures were completed successfully endoscopically. The procedure in 1 patient with a sarcoma was converted to thoracotomy because of extensive disease. Operating times ranged from 20 to 185 minutes. Diagnosis was obtained in all cases, and complete excision was performed in 33. All children were extubated in the operating room; 8 chest tubes were placed but removed within 24 hours. Hospital stay ranged from 12 hours to 4 days. Pathology included 12 foregut duplications, 7 ganglioneuromas, 6 neuroblastomas, 6 lymphomas, 3 teratomas, 2 sarcomas, and 3 other lesions. CONCLUSION: Thoracoscopy is a safe and effective method to evaluate, biopsy, and in most cases resect lesions of the anterior and posterior mediastinum in infants and children.

Cytosolic phospholipase A(2)-mediated ICAM-1 expression is calcium dependent.

BACKGROUND: Some human malignancies such as virus-related hepatocellular cancer arise in a setting of chronic inflammation. Upregulation of ICAM-1 is a seminal late event in malignant transformation following chronic inflammation. Cytosolic phospholipase A(2) (cPLA(2)) is a lipid-mediator activated by inflammatory stimuli, which has been shown to mediate ICAM-1 upregulation. As lipid mediators are known to work via calcium-dependent mechanisms in nearly all mammalian cells, we hypothesize that inflammatory-mediated ICAM-1 upregulation is dependent on both cPLA(2) and intracellular calcium. MATERIALS AND METHODS: HUVEC were chosen as a representative cell line as they emulate hepatic sinusoids and are a well-established cell model. These were grown to confluence in T-25 flasks and stimulated with TNF-alpha or LPS for 6 h. Additional groups were preincubated with AACOCF3 (a specific cPLA(2) inhibitor) or BAPTA A.M. (a specific inhibitor of intracellular Ca(2+)) prior to being exposed to inflammatory stimuli. ICAM-1 expression was determined by mean fluorescent intensity (MFI) as measured by FITC-labeled moAb to ICAM-1 via FACS. The role of intracellular Ca(2+) on cPLA(2) activity was determined by thin-layer chromatography. Groups were compared using ANOVA with Scheffe's post hoc analysis; *P < 0.05 vs control, daggerP < 0.05 vs LPS and TNF-alpha was considered significant; N > or = 4 all experimental groups. RESULTS: Both cPLA(2) and Ca(2+) inhibition significantly inhibited inflammatory upregulation of ICAM-1. Pretreatment with BAPTA A.M. attenuated HUVEC cPLA(2) activity in response to LPS. These findings suggest that appropriate molecular target suppression may prevent malignant degeneration in the presence of chronic inflammation.

Evaluation of minimally invasive approaches to achalasia in children.

BACKGROUND: Achalasia is an uncommon disease in children, but when present can result in severe disabling symptoms often requiring surgical intervention. This report describes the authors' experience with thoracoscopic (TH) and later laparoscopic Heller (LH) myotomy for definitive treatment of this disease. METHODS: Nine patients with achalasia were referred for surgical therapy. Ages ranged from 5 to 17 years and weight from 23 to 78 kg. All had undergone at least one dilatation with recurrence of symptoms. The first 4 were treated by TH and the last five by LH. The 5 LH procedures also included a partial fundoplication. RESULTS: All procedures were completed successfully using minimally invasive techniques. Operating times averaged 95 minutes for TH and 62 minutes for LH. One patient undergoing TH had a small esophageal perforation repaired primarily. The other 3 TH patients were started on clear liquids within 1 day and discharged on day 2. One patient had recurrent symptoms at 6 months and underwent a LH for an incomplete TH. All 5 LH patients were discharged on postoperative day 1. One had an esophageal perforation 4 days after operation requiring laparoscopic repair. Seven of 9 patients are asymptomatic. Studies of pH levels in 2 asymptomatic TH patients show mild gastroesophageal reflux (GER). CONCLUSIONS: Minimally invasive Heller myotomy is a safe and effective procedure in children. TH results in a slightly longer operating time and hospital stay and, without a partial fundoplication, also may be associated with a higher incidence of silent GER. From these results, we prefer LH with a Dor fundoplication for treatment of achalasia in children.

Secretory phospholipase A2 activity correlates with postinjury multiple organ failure.

UNLABELLED: Postinjury multiple organ failure (MOF) may result from overwhelming systemic hyperinflammation. Secretory phospholipase A2 (sPLA2) produces many inflammatory lipid mediators, and levels have been correlated with both the severity of patient injury and postinjury mortality. The objective of this study was to characterize the plasma activity of sPLA2 type IIa in severely injured patients and to determine whether the activity of this enzyme correlates with the subsequent development of MOF. PATIENTS: Seventeen severely injured patients at known risk for MOF had blood sampled on postinjury days 0, 1, 2, 3, and 5. DESIGN: sPLA2 activity was sequentially measured and correlated with MOF scores. RESULTS: Six patients (35%) developed MOF. In comparison with non-MOF patients, MOF patients had elevated sPLA2 activity beginning 36 hrs postinjury (MOF sPLA2, 2.4 +/- 0.97, vs. non-MOF sPLA2, 0.86 +/- 0.16 active units (AU); p < .05) and continuing over the ensuing 5 days. To rule out the possibility that stored blood components required for patient resuscitation was the source of sPLA2, the sPLA2 was measured in packed red blood cells, platelet concentrates, and fresh frozen plasma over the routine storage time. None of the products tested had elevated levels of sPLA2 compared with fresh plasma from healthy adult volunteers. CONCLUSIONS: We conclude that increased sPLA2 activity is associated with the development of postinjury MOF.

Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function.

BACKGROUND: Resuscitation with oxygen-carrying fluids is critically important in the patient with hemorrhagic shock caused by trauma. However, it is clear that a number of biologic mediators present in stored blood (packed red blood cells [PRBCs]) have the potential to exacerbate early postinjury hyperinflammation and multiple organ failure through priming of circulating neutrophils (PMNs). PolyHeme (Northfield Laboratories, Evanston, IL), a hemoglobin-based substitute that is free of priming agents, provides an alternative. We hypothesized that PMN priming would be attenuated in patients resuscitated with PolyHeme in lieu of stored blood. METHODS: Injured patients requiring urgent transfusion were given either PolyHeme (up to 20 units) or PRBCs. Early postinjury PMN priming was measured via beta-2 integrin expression, superoxide production, and elastase release. RESULTS: Treatment groups were comparable with respect to extent of injury and early physiologic compromise. PMNs from patients resuscitated with PRBCs showed priming in the early postinjury period by all three measures. No such priming was evident in patients resuscitated with PolyHeme. CONCLUSION: The use of a blood substitute in the early postinjury period avoids PMN priming and may thereby provide an avenue to decrease the incidence or severity of postinjury multiple organ failure.

Cervical spine trauma in the injured child: a tragic injury with potential for salvageable functional outcome,.

BACKGROUND/PURPOSE: Cervical spine injuries are uncommon in children, and, therefore, presumptive immobilization and diagnosis remain controversial. The purpose of this study was to review the author's experience with cervical spine injuries in children to determine the incidence, injury mechanism, pattern of injury, and subsequent functional outcome. METHODS: Fifty-two children over a 6-year period (1994 to 1999) with a cervical spine injury secondary to blunt trauma were identified (1.3% incidence). The functional independent measure (FIM) was assessed at the time of discharge in each of 3 categories: communication, feeding, and locomotion. RESULTS: Mean age of the study children was 10.7 +/- 0.7 years. Eight children (15%) were less than 5 years old, and 4 (8%) were less than 2 years old. The mechanism of injury included motor vehicle crash (52%), falls (15%), bicycle accidents (11%), sports-related injuries (10%), pedestrian accidents (8%), and motorcycle crashes (4%). Seven patients died yielding an overall mortality rate of 13%. Injuries were distributed along the cervical spinal cord as follows: 5 atlanto-occipital dislocations, 28 C1 to C3 injuries, 17 C4 to C7 injuries, and 2 ligamentous injuries. FIM scores were recorded for 18 patients. Seventeen communicated independently, 14 fed themselves independently, and 12 had independent locomotive function. CONCLUSIONS: Cervical spine injuries occur in children across a spectrum of ages. Although atlanto-occipital dislocation is a highly lethal event, children with C1 to C7 injuries have a high likelihood of reasonable independent functioning.

Operative management of injured children at an adult level I trauma center.

BACKGROUND: The geographic distribution of trauma centers results in a significant number of children being treated in adult centers. The emphasis on nonoperative management of pediatric blunt trauma has heightened concern that in adult trauma centers, an aggressive operative approach will continue to be used. We hypothesized that pediatric commitment at a Level I trauma center results in appropriate nonoperative care of injured children as established by regional pediatric trauma centers. METHODS: The records of 1,792 consecutively treated children admitted to the trauma service during a 6-year period (January of 1990 to December of 1995) were reviewed. Patients were stratified into one of three age groups: 0 to 5, 6 to 11, and 12 to 17 years of age. RESULTS: Mean age of the study patients was 10.0 +/- 0.1 years, 1,147 were boys (64%), and their mean Injury Severity Score was 7.3 +/- 0.3. The injury mechanism was blunt in 1,550 (87%) and 132 (7%) required laparotomy. In the 0- to 5-year-old blunt mechanism group, 6% underwent laparotomy or thoracotomy from 1990 to 1992. In comparison, only 1% of this age group had a laparotomy from 1993 to 1995 (p < 0.05, Fisher's exact test). A similar trend was found in the 6- to 11-year-old children after blunt injury (4% laparotomy rate from 1990 to 1992; 2% from 1993-1995). CONCLUSION: There has been a declining trend in the operative management of blunt pediatric trauma, especially in children less than 6 years old, whereas the operative management of penetrating injuries has remained stable. These data confirm that pediatric commitment in a Level I trauma center results in nonoperative treatment of injured children commensurate with that established in regional pediatric trauma centers.

Maximal human neutrophil priming for superoxide production and elastase release requires p38 mitogen-activated protein kinase activation.

HYPOTHESIS: Neutrophil priming has been implicated in the development of multiple organ failure, although the precise intracellular mechanisms that regulate neutrophil priming remain unclear. Our previous work characterized platelet-activating factor (PAF) priming of human neutrophils for concordant superoxide anion (O2-) generation and elastase degranulation. The p38 mitogen-activated protein kinase (MAPK) is activated by PAF stimulation. We hypothesized that PAF-induced human neutrophil priming for O2- and elastase release is mediated via the p38 MAPK pathway. DESIGN: Isolated neutrophils from 6 human donors were preincubated with the specific p38 MAPK inhibitor SB 203580 (1 micromol/L) or buffer (control) for 30 minutes. Cells were then primed with PAF (200 nmol/L), followed by receptor-dependent (N-formyl-methionyl-leucyl-phenylalanine, 1 micromol/L) or receptor-independent phorbol myristate acetate (PMA, 100 ng/mL) activation. SETTING: Urban trauma research laboratory. PATIENTS: Healthy volunteer donors of neutrophils. MAIN OUTCOME MEASURES: Maximal rate of O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by the cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide. RESULTS: SB 203580 significantly attenuated the generation of O2- and release of elastase from neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine but not with PMA. Independent of the activator receptor status, SB 203580 almost completely blocked the exaggerated neutrophil cytotoxic response due to PAF priming. CONCLUSIONS: The p38 MAPK pathway is required for maximal PAF-induced neutrophil priming for O2- production and elastase degranulation. Therefore, the MAPK signaling cascade may offer a potential therapeutic strategy to preempt global neutrophil hyperactivity rather than attempt to nullify the end products independently.

Nonoperative management of solid organ injuries in children results in decreased blood utilization.

BACKGROUND: The administration of blood products to injured children has been recognized as a potential risk of nonoperative management. The purpose of this study was to evaluate blood utilization in the management of solid organ injuries in pediatric blunt abdominal trauma victims. METHODS: One hundred sixty-one children (< or =16 years old) with solid organ injuries over an 8-year study period (1990 through 1997) were identified from the trauma registries at 2 urban regional trauma centers. RESULTS: Mean age of the study patients was 7.9+/-0.4 years, 95 (59%) were boys, and their mean injury severity score (ISS) was 17.8+/-1.2. Patients were divided into 4-year study cohorts (1990 through 1993 and 1994 through 1997) to examine changes in operative management and blood utilization. For each time period examined, those treated nonoperatively received fewer blood transfusions (46% v 9% and 44% v 13%, P<.05 by Fisher's Exact test), and the hospital length of stay was shorter (12.3+/-2.1 v 5.0+/-0.7 and 7.8+/-1.9 v 4.2+/-0.4 days, P<.0001 by analysis of variance/Scheffe's) compared with the laparotomy cohort. CONCLUSIONS: The appropriate nonoperative management of injured children actually reduces the risks of receiving blood transfusion and decreases the length of hospital stay compared with aggressive operative intervention. Blood transfusion should be reserved only for those injured children with solid organ injuries who are hemodynamically unstable.

Extracellular signal-related kinase 1/2 and p38 mitogen-activated protein kinase pathways serve opposite roles in neutrophil cytotoxicity.

BACKGROUND: Inflammatory stimuli rapidly activate mitogen-activated protein kinases (MAPKs) in neutrophils (PMNs). However, their role in cytotoxic function remains unknown. Elucidating the signals involved in release of cytotoxic agents from PMNs may provide new avenues for therapy in diseases of diminished or excessive PMN function. HYPOTHESIS: The p38 MAPK and extracellular signal-related kinase 1/2 (ERK1/2) modulate superoxide generation and elastase release in activated human PMNs. STUDY DESIGN: Isolated human PMNs were incubated with specific inhibitors of MAPK pathways, or vehicle control solution, before activation with the bacterial peptide f-Met-Leu-Phe. MAIN OUTCOME MEASURES: The rate of superoxide release from activated PMNs was measured by the superoxide dismutase-inhibitable reduction of cytochrome-c. Elastase release from PMNs was determined by cleavage of the substrate Ala-Ala-Pro-Val-pNA. RESULTS: Superoxide release from activated PMNs was inhibited by blockade of p38 MAPK activation but unaffected by blockade of ERK1/2. Conversely, elastase release was unaffected by p38 MAPK inhibition and increased by ERK1/2 inhibition. CONCLUSIONS: Activation of p38 MAPK promotes superoxide release from PMNs activated by f-Met-Leu-Phe. The ERK1/2 pathway may serve as a negative feedback mechanism for granule exocytosis.

Cardiopulmonary bypass renders patients at risk for multiple organ failure via early neutrophil priming and late neutrophil disability.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response syndrome (SIRS) and these patients are recognized to be at increased risk for delayed infectious complications. We have documented that circulating neutrophils (PMNs) from patients manifesting SIRS have evidence of early postinjury priming for cytotoxicity. Consequently, we hypothesized that CPB would result in early postoperative PMN hyperresponsiveness (priming). MATERIALS AND METHODS: Six patients (mean age 50 +/- 2.9 years) who underwent CPB for CABG had sequential blood samples obtained perioperatively. PMNs were isolated and superoxide anion (O(-)(2)) generation (nmol O(-)(2)/3.75 x 10(5) PMNs/min) was measured by reduction of cytochrome c after exposure to fMLP, C5a, or PMA; elastase release (% total PMN elastase content) was measured by cleavage of AAPV-pNA after exposure to fMLP or C5a. RESULTS: PMNs were activated for increased elastase release 6 h after initiation of CPB. Significant PMN priming for O(-)(2) production was discovered at 3, 6, and 12 h following CPB and for elastase release at 3 and 6 h after CPB. At 2 to 3 days after CPB, O(-)(2) generation was significantly less than that of the preoperative control. Neutrophil primability with PAF was detected at 6 h after CPB. A similar defect in PAF-primable O(-)(2) production was seen 2 and 3 days post-CPB. Direct PMN interrogation with the receptor-independent activator PMA revealed loss of integrity of the NADPH oxidase at 2 and 3 days following CPB. CONCLUSIONS: A vulnerable window exists between 3 and 12 h after CPB when PMNs are primed for enhanced cytotoxicity via O(-)(2) production and elastase release. Paradoxically, PMN oxidase integrity becomes deficient 48 h post-CPB, while protease degranulation remains intact. These events render the bypass patient at risk for multiple organ failure via both early PMN-mediated tissue injury and delayed infectious complications.

Release of anti-inflammatory mediators after major torso trauma correlates with the development of postinjury multiple organ failure.

BACKGROUND: Soluble tumor necrosis factor receptor (sTNFr) and interleukin-1 receptor antagonist (IL-1ra) have been identified as endogenous inhibitors of TNF-alpha and IL-1beta. While TNF-alpha and IL-1beta levels are not systematically elevated in postinjury patients who developed multiorgan failure (MOF), their involvement at the tissue level has been suggested. Our study hypothesis was that levels of sTNFr-I and IL-1ra would discriminate patients at risk for postinjury MOF. METHODS: Serial plasma levels of sTNFr and IL-1ra were measured in 29 trauma patients at high risk for postinjury MOF. RESULTS: sTNFr-I levels were higher in MOF compared with non-MOF patients at 12, 84, and 132 hours postinjury. MOF patients also had higher IL-1ra values 36, 60, 84, and 132 hours postinjury. CONCLUSIONS: Anti-inflammatory mechanisms are activated after trauma. Since increased levels of sTNFr and IL-1ra correlate with postinjury MOF, they may contribute to our understanding of the pathogenesis as well as prediction of outcome. High levels of antagonists to TNF-alpha and IL-1beta suggest tissue level involvement of these cytokines in postinjury hyperinflammation.

Driveway crush injuries in young children: a highly lethal, devastating, and potentially preventable event.

BACKGROUND/PURPOSE: The aim of this study was to investigate driveway-related injuries in children, identify associated risk factors, and evaluate outcome compared with other mechanisms of blunt trauma. METHODS: A 6-year review (1991 to 1996) of pediatric (age less than 18 years) pedestrian injuries treated at two urban trauma centers was conducted: one regional pediatric trauma center and one level I trauma center with pediatric commitment. Five hundred twenty-seven children injured in pedestrian accidents were identified from the trauma registry; 51 children (10%) sustained traumatic injuries as a result of being struck in their driveway. Data are reported as mean +/- SEM. RESULTS: Children less than 5 years of age (n = 41) had an injury severity score (ISS) of 12.3+/-2.3, 15 (37%) sustained closed head injury, 13 (37%) had torso trauma, 19 (46%) skeletal trauma, and eight (20%) died. Children > or = 5 years old (n = 10) had an ISS of 10.7+/-2.4, three (30%) sustained closed head injury, four (40%) torso trauma, six (60%) skeletal trauma, and none died. In contrast, all other pediatric pedestrian accidents analyzed over the same time period had a mortality rate of only 2% (11 of 476). CONCLUSIONS: Pediatric driveway trauma carries a significant risk of head injury and a 10-fold increase in mortality in children under 5 years of age when compared with all other pediatric pedestrian accidents. More emphasis must be placed on injury prevention and public education to prevent this devastating mechanism of injury in these young, vulnerable children.

Is routine pathological evaluation of pediatric hernia sacs justified?

BACKGROUND/PURPOSE: Herniorrhaphy is the most common general surgical procedure performed on children, and hernia sac material is one of the most common tissue specimens microscopically examined in the authors' surgical pathology laboratory. The risk of accidental vas deferens ligation has prompted the recommendation that all hernia sacs be examined pathologically. The authors hypothesized that the incidence of unrecognized vas deferens or epididymis ligation is actually very low and may not warrant routine pathological examination of all pediatric hernia sacs. METHODS: Over a 3-year period (1994 to 1996), pathology reports from all hernia repairs at the authors' institution were reviewed. A total of 1,494 inguinal hernia sacs were pathologically evaluated from 1,077 pediatric patients (417 were bilateral). Pathological diagnoses not affecting clinical management (ie, chronic inflammation, irritated hernia sacs, embryonal remnants, adrenal cortical rests) were classified as incidental findings. Identification of true vas deferens was classified as a positive finding. RESULTS: The study population had a mean age of 3.9 +/- 0.1 years and 963 (89%) were boys. The incidence of vas deferens injury from herniorrhaphy was found to be 0.13% (2 of 1,494), and these were recognized by the pediatric surgeon in the operating room. CONCLUSIONS: When vas deferens injury is suspected, the sample should always be sent to the pathology department for confirmation. However, no occult carcinoma or other pathology was identified, and the remainder of the histological findings did not change the clinical treatment of any child. Given a fixed cost of pathological analysis, elimination of routine hernia sac examination may result in substantial annual savings. Therefore, in the current era of cost containment, recommendations for routine pathological examination of excised pediatric hernia sacs should be reevaluated.

Primed neutrophils require phosphatidic acid for maximal receptor-activated elastase release.

BACKGROUND: Priming of neutrophils (PMNs) for protease release is believed to be central to the pathogenesis of PMN-mediated tissue injury observed in ARDS/MOF. Defining the intracellular signaling pathways involved with this excessive protease release may aid in establishing future therapies for ARDS. Phospholipase D (PLD) production of phosphatidic acid (PA) is thought to be pivotal in reactive oxygen species generation but its role in degranulation (i. e., protease release) remains unclear. Our hypothesis was that primed neutrophils require PLD production of PA for maximal activated release of elastase. METHODS: Isolated human PMNs were incubated with a well described antagonist of PA production, ethanol (ETOH, 100-1000 mg/dL), and then primed (PAF, 200 nM) followed by activation (fMLP, 1 microM). To mimic fMLP receptor-dependent activation, PMNs were primed and then directly activated with exogenous dioctanoyl l-alpha-phosphatidic acid (PA8, 0.5-200 microM). To confirm the importance of PA in elastase release, PA8 was given to primed-activated PMNs after ethanol pretreatment in an attempt to recover the maximal response. Elastase release was measured by the cleavage of AAPV-pNA. RESULTS: PA blockade with ETOH attenuated PAF-primed/fMLP-activated PMN elastase release in a dose-dependent manner. Exogenous PA8 reproduced maximally primed-activated PMN elastase release, and furthermore, PA8 was able to restore maximal elastase release following ethanol attenuation. CONCLUSIONS: Elastase release from PAF-primed/ fMLP-activated neutrophils is dependent on PA production. Thus, PA production appears to be involved in both oxidant-dependent and independent mechanisms of neutrophil cytotoxicity and may be a potential therapeutic target in the treatment of hyperinflammatory diseases such as ARDS/MOF.

Ultrasound is an effective triage tool to evaluate blunt abdominal trauma in the pediatric population.

BACKGROUND: Although computed tomography has been considered the diagnostic modality of choice for pediatric patients with blunt abdominal trauma (BAT), it is costly, time-consuming, requires sedation, and may be associated with complications in young children. Abdominal ultrasonography (US) is a promising modality in the evaluation of BAT that is quick, noninvasive, repeatable, and cost-effective. We hypothesized that emergency department US, performed by trauma surgeons, is a useful triage tool for pediatric BAT that reduces the need for computed tomography. METHODS: The 230 children (<18 years old) with suspected BAT were initially evaluated with US in the emergency department by surgeons. Subsequent computed tomographic scan or exploratory laparotomy was performed as indicated by the key clinical pathway. RESULTS: Twelve children (5.2%) had documented intra-abdominal injuries. All five injured children with significant intraperitoneal fluid were identified by US. Of the seven patients who had intra-abdominal injury not detected by US, six sustained solid organ injuries that were managed nonoperatively. Extrapolated reductions in hospital charges due to the decreased number of computed tomographic scans total $130,000. CONCLUSIONS: Using US as a triage tool may dramatically reduce the cost of pediatric BAT evaluation while being able to quickly identify significant intraperitoneal fluid that requires further evaluation and possible laparotomy.

ICAM-1-CD18 interaction mediates neutrophil cytotoxicity through protease release.

Interaction of the beta2-integrin complex on the polymorphonuclear neutrophil (PMN) with intercellular adhesion molecule-1 (ICAM-1) has been implicated in PMN-mediated cytotoxicity. This study examined interaction of the CD11a, CD11b, and CD18 subunits of the beta2-integrin with ICAM-1, transfected into Chinese hamster ovarian (CHO) cells to avoid effects of other adhesion molecules. Incubation of quiescent PMNs with wild-type and ICAM-1-transfected CHO cells produced nominal cell lysis. Similarly, when phorbol myristate acetate (PMA)-activated PMNs were incubated with wild-type CHO cells, minimal cytotoxicity was produced. However, when ICAM-1-transfected CHO cells were incubated with PMA-activated PMNs, 40% cell lysis occurred. Blockade with a monoclonal antibody (MAb) to ICAM-1 or MAbs to CD11a, CD11b, or CD18 reduced PMN-mediated cytotoxicity to baseline. To examine the role of adhesion in cytotoxicity, we studied beta2-integrin-mediated PMN adhesion to ICAM-1-transfected CHO cells and found that MAbs for CD11a, CD11b, and CD18 all abrogated PMN cytotoxicity despite disparate effects on adhesion. To assess the role of CD18, beta2-integrin subunits were cross-linked, and CD18 alone mediated protease release. Moreover, ICAM-1 was immunoprecipitated from transfected CHO cells and incubated with PMNs. This soluble ICAM-1 provoked elastase release, similar to PMA, which could be inhibited by MAbs to CD18 but not MAbs to other beta2-integrin subunits. In addition, coincubation with protease inhibitors eglin C and AAPVCK reduced PMN-mediated cytotoxicity to control levels. Finally, ICAM-1-transfected CHO cells were exposed to activated PMNs from a patient with chronic granulomatous disease that caused significant cell lysis, equivalent to that of PMNs from normal donors. Collectively, these data suggest that ICAM-1 provokes PMN-mediated cytotoxicity via CD18-mediated protease release.

Hypertonic saline activates lipid-primed human neutrophils for enhanced elastase release.

BACKGROUND: Ongoing clinical trials have revived interest in hypertonic saline (HTS) for postinjury resuscitation; these studies have documented serum Na+ concentrations > or = 170 mmol/L. Recent animal studies have shown that HTS enhances T-cell and monocyte function, but effects on the polymorphonuclear neutrophil (PMN) remain unclear. The postinjury lipid mediators platelet-activating factor (PAF) and leukotriene B4 (LTB4) have been implicated in PMN priming for cytotoxicity, which is believed to be important in the pathogenesis of multiple organ failure. We hypothesized that HTS would stimulate PMN superoxide (O2-) and elastase release from PAF- and LTB4-primed PMNs. METHODS: Isolated PMNs from five donors were primed for 5 minutes with 200 nmol/L PAF or 1 micromol/L LTB4 in Kreb's-Ringer's phosphate with dextrose at a Na+ concentration of 140 mmol/L (normal serum Na+ concentration), pelleted, and resuspended in Kreb's-Ringer's phosphate with dextrose for 10 minutes at a Na+ concentration of 130 to 170 mmol/L. O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide. RESULTS: HTS with Na+ concentration up to 170 mmol/L had no significant effect on O2- production or elastase release from quiescent cells. Na+ concentration of 160 and 170 mmol/L, however, activated PAF- and LTB4-primed PMNs for enhanced elastase release with no effect on O2- production. CONCLUSION: In clinically relevant concentrations, elevated Na+ activates lipid-primed neutrophils for enhanced elastase degranulation. Consequently, the administration of HTS in the early postinjury resuscitation period, when PMNs are maximally primed, may activate PMN elastase release and thereby promote the development of multiple organ failure.