Entry of gut lymph into the circulation primes rat neutrophil respiratory burst in hemorrhagic shock.

OBJECTIVE: Endothelial cell injury by polymorphonuclear neutrophil (neutrophil [PMN]) respiratory burst after trauma and hemorrhagic shock (T/HS) predisposes subjects to acute respiratory distress syndrome and multiple organ failure. T/HS mesenteric lymph injures endothelial cell and lymph duct ligation (LDL) before T/HS prevents pulmonary injury. We investigated the role of mesenteric lymph in PMN priming by T/HS. DESIGN: Prospective experiment in rats. SETTING: University hospital laboratory. SUBJECTS: Adult male rats. INTERVENTIONS: Mesenteric lymph was obtained from rats undergoing T/HS (30 mm Hg, 90 mins) or sham shock (T/SS). Plasma was harvested from uninstrumented control (UC), T/HS, T/SS, and T/HS+LDL rats. PMNs were isolated from UC, T/HS, and T/HS+LDL rats. MEASUREMENTS AND MAIN RESULTS: PMNs from UC rats were incubated in buffer, 1% T/HS lymph, and 1% T/SS lymph. PMNs from UC rats were incubated in UC, T/HS, T/SS, and T/HS+LDL plasma. PMN respiratory burst was initiated by using macrophage inflammatory protein (MIP)-2/platelet-aggregating factor (PAF) or phorbol myristate acetate. Cytosolic calcium ([Ca2+]i) responses to MIP-2/PAF were assayed in PMN from UC, T/HS, and T/HS+LDL rats. PMN preincubated in T/HS lymph showed significant elevations in MIP/PAF-elicited respiratory burst compared with T/HS lymph or buffer only (p <.05; analysis of variance/Tukey's test). T/HS lymph incubation also increased (p <.05) phorbol myristate acetate elicited respiratory burst compared with buffer or T/SS. Preincubation in T/HS plasma increased MIP-2/PAF-elicited respiratory burst (p <.05) compared with UC or T/SS plasma. LDL blocked T/HS priming of respiratory burst. Control PMN [Ca2+]i responses to MIP-2 and PAF were low. T/SS PMN were significantly more responsive, but the T/HS PMN showed still higher responses (p <.01). LDL reversed the priming of [Ca2+]i responses by T/HS (p <.01). CONCLUSIONS: PMNs are primed by T/HS lymph but not T/SS lymph and by T/HS plasma but not T/SS plasma. LDL before shock prevents T/HS plasma from priming PMN. The magnitude of respiratory burst found here paralleled the [Ca2+]i responses seen to receptor dependent initiating agonists. Mesenteric lymph is both necessary and sufficient to prime PMN after T/HS in the rat, and it primes PMN in part by enhancing [Ca2+]i responses to G-protein coupled chemoattractants. Mesenteric lymph mediates postshock PMN dysfunction.

Induction of hypoxia-inducible factor-1alpha and activation of caspase-3 in hypoxia-reoxygenated bone marrow stroma is negatively regulated by the delayed production of substance P.

The bone marrow (BM), which is the major site of immune cell development in the adult, responds to different stimuli such as inflammation and hemorrhagic shock. Substance P (SP) is the major peptide encoded by the immune/hemopoietic modulator gene, preprotachykinin-1 (PPT-I). Differential gene expression using a microarray showed that SP reduced hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA levels in BM stroma. Because long-term hypoxia induced the expression of PPT-I in BM mononuclear cells, we used timeline studies to determine whether PPT-I is central to the biologic responses of BM stroma subjected to 30-min hypoxia (pO(2) = 35 mm Hg) followed by reoxygenation. HIF-1alpha mRNA and protein levels were increased up to 12 h. At this time, beta-PPT-I mRNA was detected with the release of SP at 16 h. SP release correlated with down-regulation of HIF-1alpha to baseline. A direct role for SP in HIF-1alpha expression was demonstrated as follows: 1) transient knockout of beta-PPT-I showed an increase in HIF-1alpha expression up to 48 h of reoxygenation; and 2) HIF-1alpha expression remained baseline during reoxygenation when stroma was subjected to hypoxia in the presence of SP. Reoxygenation activated the PPT-I promoter with concomitant nuclear translocation of HIF-1alpha that can bind to the respective consensus sequences within the PPT-I promoter. SP reversed active caspase-3, an indicator of apoptosis and erythropoiesis, to homeostasis level after reoxygenation of hypoxic stroma. The results show that during reoxgenation the PPT-I gene acts as a negative regulator on the expression of HIF-1alpha and active caspase-3 in BM stroma subjected to reoxygenation.

The use of capnography in the air medical environment.

We can count on two things when we receive a call as part of an air medical transport team--the patient is in critical condition, and time is of the essence. Whether the patient has experienced trauma from a motor vehicle crash, has fallen, or has suffered an insult as a consequence of poor health, our technique, skill, and judgment are tested constantly. Fortunately, we have equipment at our disposal to make our job easier. One of the more difficult aspects and responsibilities of air medical transport teams is placement of an endotracheal tube (ET). Along with the techniques used for successful endotracheal intubation (ETI), available technology can maximize patients' ventilatory status using an instrument that detects expired carbon dioxide (CO(2)) levels.

Hematopoietic failure after hemorrhagic shock is mediated partially through mesenteric lymph.

OBJECTIVE: To determine whether hemorrhagic shock-induced bone marrow failure is mediated by the gut through the production of toxic mesenteric lymph and whether shock-induced bone marrow failure could be prevented by division of the mesenteric lymphatics. DESIGN: Prospective, controlled study. SETTING: University surgical research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats were divided into five groups: unmanipulated controls (n = 12), hemorrhagic shock with laparotomy (n = 8), hemorrhagic shock with mesenteric lymph duct ligation (n = 10), sham shock with laparotomy (n = 6), and sham shock with mesenteric lymph duct ligation (n = 7). At either 3 or 6 hrs after resuscitation, bone marrow was obtained for determination of early (cobblestone forming cells) and late (granulocyte-macrophage colony forming unit and erythroid burst forming unit) hematopoietic progenitor cell growth. Parallel cultures were plated with plasma (1% and 2% v/v) from all groups to determine the effect of lymphatic ligation on hematopoiesis. MEASUREMENTS AND MAIN RESULTS: Bone marrow cellularity, cobblestone forming cells, granulocyte-macrophage colony forming unit, and erythroid burst forming unit growth in rats subjected to hemorrhagic with lymph duct ligation were similar to those observed in sham-treated animals and significantly greater than in rats subjected to shock and laparotomy without lymphatic duct ligation. Plasma from rats subjected to shock without lymph ligation was inhibitory to hematopoietic progenitor cell growth. In contrast, this shock-induced inhibition was not observed with plasma obtained from shocked rats that underwent mesenteric lymph ligation. CONCLUSIONS: Hemorrhagic shock suppresses bone marrow hematopoiesis as measured by a decrease in early and late progenitor cell growth. This suppression appears mediated through mesenteric lymph as the effect is abrogated by mesenteric lymph duct ligation. These data clearly demonstrate a link between the gut and bone marrow failure after hemorrhagic shock

Free fluid on abdominal computed tomography without solid organ injury after blunt abdominal injury does not mandate celiotomy.

BACKGROUND: Mandatory celiotomy has been proposed for all patients with unexplained free fluid on abdominal computed tomography (CT) scanning after blunt abdominal injury. This recommendation has been based upon retrospective data and concerns over the potential morbidity from the late diagnosis of blunt intestinal injury. This study examined the rate of intestinal injury in patients with free fluid on abdominal CT after blunt abdominal trauma. METHODS: This study was a multicenter prospective series of all patients with blunt abdominal trauma admitted to four level I trauma centers over 22 months. Data were collected concurrently at the time of patient enrollment and included demographics, injury severity score, findings on CT scan, and presence or absence of blunt intestinal injury. This database was specifically queried for those patients who had free fluid without solid organ injury. RESULTS: In all, 2,299 patients were evaluated. Free fluid was present in 265. Of these, 90 patients had isolated free fluid with only 7 having a blunt intestinal injury. Conversely, 91% of patients with free fluid did not. All patients with free fluid were observed for a mean of 8 days (95% confidence interval 6.1 to 10.4, range 1 to 131). There were no missed injuries. CONCLUSIONS: Free fluid on abdominal CT scan does not mandate celiotomy. Serial observation with the possible use of other adjunctive tests is recommended.

Early trauma polymorphonuclear neutrophil responses to chemokines are associated with development of sepsis, pneumonia, and organ failure.

OBJECTIVES: The modulation of polymorphonuclear neutrophil (PMN) function by injury is unpredictable, and can predispose either to hyperimmune states (adult respiratory distress syndrome [ARDS], multiple organ failure) or to immune dysfunction, infection, and sepsis. Such outcomes have been related to excess production of the CXC chemokine interleukin (IL)-8, but PMN responses to IL-8 are mediated by both the relatively stable and IL-8 specific CXC receptor 1 (CXCR1) and the labile, promiscuous CXCR2. We hypothesized that progression to septic and multiple organ failure outcomes could be related to early differences in PMN CXC receptor status. METHODS: PMNs were isolated 12 +/- 3 hours after injury from 15 major trauma patients (Injury Severity Score of 34 +/- 2, 11 men and 4 women, age 36 +/- 4 years) who survived at least 7 days. Volunteer normal PMNs (n = 6 donors) were studied for comparison. Cells were stimulated either with the CXCR2 specific agent growth-related oncogene-alpha, or with IL-8, which stimulates CXCR1 and CXRR2. Receptor response was assessed as the mobilization of cell calcium. The development of ARDS, sepsis, and pneumonia was assessed according to standardized criteria. Day 1 receptor activity in the clinical groups was then compared by analysis of variance with Tukey's or t tests as appropriate. RESULTS: In patients that were otherwise comparable, CXCR2 responses were markedly diminished in the PMNs of patients who went on to sepsis and pneumonia, but were elevated in PMNs from the patients who went on to ARDS. CXCR1 responses were modestly lower in trauma patients than volunteers, but showed no significant variations among the various clinical outcome groups. CONCLUSION: The activity of PMN CXCR2 receptors soon after injury may be reflected in the later clinical sequelae of PMN activity. High CXCR2 activity may correlate with PMN hyperfunction and outcomes such as ARDS, whereas the loss of CXCR2 function in inflammatory environments may impair PMN functions in a manner that predisposes to pneumonia or sepsis. Early responses of PMN CXC receptors to injury may influence the clinical course of trauma patients.

Trauma inhibits erythroid burst-forming unit and granulocyte-monocyte colony-forming unit growth through the production of TGF-beta1 by bone marrow stroma.

OBJECTIVE: To examine the effect of trauma plasma on clonogenic progenitor cultures. SUMMARY BACKGROUND DATA: Severely injured trauma patients often experience altered hematopoietic functions, manifested by an increased susceptibility to infection and the development of a persistent anemia. Experimental and clinical data suggest that trauma results in the release of cytokines into the plasma that have hematopoietic regulatory function, but few studies have examined human bone marrow. METHODS: Plasma was obtained from 42 severely injured patients admitted to the surgical intensive care unit from days 1 to 15 after injury. Bone marrow and normal plasma were obtained from volunteers. Bone marrow mononuclear cells were isolated and plated for granulocyte-monocyte colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth. Parallel cultures were incubated with 2% (v/v) trauma or normal plasma. Additional cultures were plated with neutralizing concentrations of antibodies to transforming growth factor (TGF)-beta1 and MIP-1alpha. Circulating plasma TGF-beta1 was determined by bioassay. mRNA from bone marrow stromal cultures was extracted and probed for TGF-beta1 and macrophage inflammatory protein (MIP)-1alpha. RESULTS: Trauma plasma suppressed CFU-GM and BFU-E colony growth by 40% to 60% at all time periods after injury compared with cultures incubated with normal plasma. Using a noncontact culture system, the authors showed that this inhibition of BFU-E and CFU-GM colony growth was mediated by bone marrow stroma. The inhibition appeared to be due to soluble plasma-induced bone marrow stromal products that did not require direct cell-cell contact. The addition of anti-TGF-beta1 antibodies reversed the suppressive effect of trauma plasma on CFU-GM and BFU-E colony growth during the early but not late time points after injury. Trauma but not normal plasma induced TGF-beta1 mRNA in bone marrow stroma. CONCLUSIONS: Trauma plasma inhibits bone marrow BFU-E and CFU-GM colony growth for up to 2 weeks after injury. This inhibition is mediated through the interaction of trauma plasma with bone marrow stroma. TGF-beta1 production by bone marrow stroma appears to plays an important role in the early but not late bone marrow suppression after injury.

Injury-enhanced calcium mobilization in circulating rat neutrophils models human PMN responses.

G-protein coupled (GPC) chemoattractants are important neutrophil (PMN) activators in human shock and sepsis, acting in part by increasing cytosolic calcium ([Ca2+]i). Rats are widely used as laboratory models of shock and sepsis, but reports of [Ca2+]i flux in circulating rat PMN are rare. Moreover, the [Ca2+]i values reported often differ markedly from human systems. We developed study methods where basal [Ca2+]i values in circulating rat PMN were comparable to human PMN, but rat PMN still mobilized calcium poorly after stimulation. Trauma (laparotomy) did not change rat PMN basal [Ca2+]i, but induced brisk [Ca2+]i responses to chemokine and lipid mediators that approximated human PMN responses. This was associated with marked loading of microsomal calcium stores. Formyl peptides still mobilized calcium less well in rat than human PMN. Normal rat PMN appear to circulate in a less mature or primed form than human PMN. A very limited injury rapidly converts rat PMN to a more activated phenotype. PMN thus activated act quite similar to human PMN in terms of GPC receptor-mediated calcium mobilization. Trauma enhances rat PMN responses to GPC agonists at least in part by loading cell calcium stores.

The immunomodulatory effects of damage control abdominal packing on local and systemic neutrophil activity.

BACKGROUND: Damage control laparotomy (DCL) with abdominal packing has become commonplace after major trauma, but the immune consequences of DCL are unknown. METHODS: We collected 37 fluid samples from laparotomy pads (LPF) removed from 28 patients 1 hour to 7 days after DCL. Samples from eight patients who underwent serial packing were assayed for their mediator content and effects on neutrophil (PMN) function. Respiratory burst (RB) to N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate (PMA), as well as PMN calcium ([Ca2+]i) mobilization by GRO-alpha and platelet-activating factor were studied using dihydrorhodamine and fura-2-acetoxymethyl ester fluorescence. Brief exposure to 20% LPF (LPF20) modeled LPF acting on peritoneal PMNs and 2% LPF (LPF2) modeled the systemic effects on PMNs. Endotoxin (ETX), GRO-alpha, and leukotriene B4 were assayed by enzyme-linked immunosorbent assay. Data analysis was by analysis of variance with Dunn's comparisons or the Mann-Whitney test when indicated. RESULTS: LPF increased N-formyl- methionyl-leucyl-phenylalanine-induced RB from 0.4 +/- 0.1 x 103 counts per second (control) to 0.7 +/- 0.1 (LPF2) to 1.3 +/- 0.3 (LPF20) (p < 0.05), with LPF2 increasingly active at later times after injury. PMA-elicited RB was primed only by LPF2 from < 24 hours. Both LPF2 and LPF20 markedly suppressed GRO-alpha [Ca2+]i flux. Suppression by LPF2 was maximal at < 24 hours, abating after 48 hours. Suppression of GRO-alpha response was dose dependent: 150 +/- 8 nmol/L in control PMNs, 97 +/- 19 after LPF2, and 59 +/- 4 after LPF20 (all p < 0.05). [Ca2+]i flux after 1 nmol/L platelet-activating factor was only suppressed (from 181 +/- 14 nmol/L to 149 +/- 15 nmol/L, p < 0.05) by LPF20. LPF contained ETX, GRO-alpha, and leukotriene B4 at 10- to 20-fold plasma concentration in trauma patients. CONCLUSION: DCL results in peritoneal ETX and mediator accumulation even when cultures are sterile. LPF exposure primes PMN RB elicited by nonreceptor- (PMA) or receptor-coupled agonists that resist receptor desensitization. Conversely, LPF suppresses PMN responses to agonists that undergo receptor desensitization at high mediator concentrations. PMN dysfunction in such circumstances probably reflects a concomitant priming of some cell functions (e.g., RB) and desensitization of other (receptor-dependent) functions after an exposure to concentrated mediators. Peritoneal mediator production after DCL may be ETX driven, and may contribute to systemic inflammatory response syndrome. DCL trades early hemostasis for later inflammation. This should be considered in planning management strategies.

Increased incidence of sepsis and altered monocyte functions in severely injured type A- glucose-6-phosphate dehydrogenase-deficient African American trauma patients.

OBJECTIVE: To determine whether trauma patients with the common, type A- glucose-6-phosphate dehydrogenase (G6PD) deficiency have an aggravated inflammatory response, increased incidence of septic complications, and/or more profound alterations in leukocyte functions compared with nondeficient trauma patients. SETTINGS: Intensive and surgical care units of a trauma center and flow cytometry and experimental laboratories at a teaching university hospital. DESIGN: Prospective cohort clinical study with measurements on days 2 and 5 postinjury. Monocyte and neutrophil oxidant content, apoptosis, and CD11b expression and plasma cytokine levels were compared between G6PD-deficient and nondeficient patients. PATIENTS: A total of 467 male African American trauma patients were screened for the deficiency. Forty-four type A-202/376 G6PD-deficient patients were identified and enrolled in the study; 43 nondeficient patients were also enrolled and were matched by age, clinical criteria of injury severity, and type of trauma. MAIN RESULTS: After severe injury (Injury Severity Score, > or =16), 50% of the deficient and 6.2% of nondeficient patients developed sepsis with positive bacterial blood cultures. In deficient patients, the frequency of bronchial (75%) and wound infections (25%) was also increased compared with nondeficient patients (32% and 0%). The durations of systemic inflammatory response syndrome, Sepsis Syndrome, and days on antibiotics were three times longer in deficient than in nondeficient individuals. However, adult respiratory distress syndrome occurred in 37% of both groups. Anemia was more severe in the deficient than nondeficient patients from day 10 posttrauma. On day 5, the peroxide content was doubled, apoptosis was decreased, and CD11b expression was increased in monocytes from deficient patients compared with cells from nondeficient patients. On day 5, the plasma interleukin (IL)-10 concentration was significantly lower in deficient than nondeficient patients, whereas tumor necrosis factor-alpha, IL-6, and IL-8 levels were similar. After moderate injuries (Injury Severity Score, 9-16), the deficiency was not associated with adverse clinical effects, and the trauma-induced changes in leukocyte function were similar in deficient and nondeficient patients. CONCLUSIONS: The common type A- G6PD deficiency predisposes septic complications and anemia in trauma patients after severe injuries as defined by an Injury Severity Score of > or =16. This adverse clinical course is accompanied by altered monocyte functions manifested as augmented oxidative stress, a decreased apoptotic response, increased cell adhesion properties, and a diminished IL-10 response.

PAF-mediated Ca2+ influx in human neutrophils occurs via store-operated mechanisms.

Many inflammatory mediators activate neutrophils (PMN) partly by increasing cytosolic calcium concentration ([Ca2+]i). Modulation of PMN [Ca2+]i might therefore be useful in regulating inflammation after shock or sepsis. The hemodynamic effects of traditional Ca2+ channel blockade, however, could endanger unstable patients. Store-operated calcium influx (SOCI) is known now to contribute to Ca2+ flux in "nonexcitable" cells. Therefore, we studied the role of SOCI in human PMN responses to the proinflammatory ligand PAF. PMN [Ca2+]i was studied by spectrofluorometry with and without external calcium. We studied the effects o

G-protein receptor responses in trauma neutrophils.

BACKGROUND: Trauma modulates polymorphonuclear neutrophil (PMN) function, predisposing to organ failure and infection. Many chemoattractants released by injury activate PMNs via G-protein-coupled (GPC) receptors, which elevate PMN cytosolic calcium ([Ca2+]i). Nonetheless, PMN GPC receptor function after injury is unstudied. METHODS: PMNs from 11 major trauma patients (Injury Severity Score = 31 +/- 3, eight men and three women, age = 38 +/- 3) were obtained on days 1, 3, and 7 after injury. Nine developed organ failure and one died. PMNs were exposed to interleukin-8 (IL-8), growth regulated oncogene-alpha (GRO-alpha), and platelet-activating factor (PAF) to stimulate the CXCR1, CXCR2, and PAF receptors. [Ca2+]i flux measurements were used to quantify receptor responses. Receptor responses to individual as well as serial GPC agonists were studied over the week after injury and compared with the responses of PMNs from healthy volunteers (n = 10-23). Results were evaluated by one-way analysis of variance, and paired and unpaired t tests. RESULTS: Responses to GRO-alpha and PAF were significantly depressed early after injury (p < 0.01). Responses to all agonists tested tended to be lowest on day 1, to peak on day 3, and to decrease again by day 7, but variations in response to GRO-alpha were the most marked (p < 0.03, analysis of variance). Whereas GRO-alpha primed IL-8 and IL-8 primed PAF in normal PMNs, GRO-alpha paradoxically suppressed IL-8 responses and IL-8 suppressed PAF responses in trauma PMNs. PAF priming of IL-8 responses was unaffected by injury. CONCLUSION: Receptor responses to individual GPC agonists are suppressed early after trauma, but increase by day 3. Normal chemokine priming of PMN calcium mobilization is reversed by injury; priming by PAF is intact. PMN GPC responses depend on the sequence in which agonists are encountered. Injury appears to alter these interactions, thus priming some aspects of PMN function while simultaneously suppressing others.

Emergency department discharge of patients with a negative cranial computed tomography scan after minimal head injury.

OBJECTIVE: To determine the negative predictive value of cranial computed tomography (CT) scanning in a prospective series of patients and whether hospital admission for observation is mandatory after a negative diagnostic evaluation after minimal head injury (MHI). SUMMARY BACKGROUND DATA: Hospital admission for observation is a current standard of practice for patients who have sustained MHI, despite having undergone diagnostic studies that exclude the presence of an intracranial injury. The reasons for this practice are multifactorial and include the perceived false-negative rate of all standard diagnostic tests, the belief that admission will allow prompt diagnosis of occult injuries, and medicolegal considerations about the risk of early discharge. METHODS: In a prospective, multiinstitutional study during a 22-month period at four level I trauma centers, all patients with MHI were evaluated using the following protocol: a standardized physical and neurologic examination in the emergency department, cranial CT scanning, and then admission for observation. MHI was defined as either a documented loss of consciousness or evidence of posttraumatic amnesia and an emergency department Glasgow Coma Scale score of 14 or 15. Outcomes were measured at 20 hours and at discharge and included clinical deterioration, need for craniotomy, and death. RESULTS: Two thousand one hundred fifty-two consecutive patients fulfilled the study protocol. The CT was interpreted as negative for intracranial injury in 1,788, positive in 217, and equivocal in 119. Five patients with CT scans initially interpreted as negative required intervention. There was one craniotomy in a patient whose CT scan was initially interpreted as negative. This patient had facial fractures that required surgical intervention and elevation of depressed intracranial fracture fragments. The negative predictive power of a cranial CT scan based on the preliminary reading of the CT scan and defined by the subsequent need for neurosurgical intervention in the population fully satisfying the protocol was 99.70%. CONCLUSIONS: Patients with a cranial CT scan, obtained on a helical CT scanner, that shows no intracerebral injury and who do not have other body system injuries or a persistence of any neurologic finding can be safely discharged from the emergency department without a period of either inpatient or outpatient observation. Implementation of this practice could result in a potential decrease of more than 500,000 hospital admissions annually.

The utility of venous lactate to triage injured patients in the trauma center.

BACKGROUND: Field triage criteria for trauma patients results in over-triage rates of 30% to 50% to achieve under-triage rates of 10%. This large number of patients may stress trauma center resources. Elevated arterial lactate (ALAC) levels have been shown to be a marker of serious injury but the need for arterial sampling limits the utility of the determination. The goal of this study was: 1) to determine the correlation between venous lactate (VLAC) and ALAC; 2) to determine whether VLAC could identify those patients with serious injuries; and 3) to compare an elevated VLAC level against standard triage criteria (STC) in their ability to identify major injury. STUDY DESIGN: Arterial and venous samples for blood gas and lactate analyses were obtained in 375 patients within 10 minutes of patient arrival to the trauma center. Arterial and venous samples were drawn within 2 minutes of each other, placed on ice, and analyzed within 10 minutes of sampling. The location of sampling was left to physician discretion. Data collected included injury mechanism, demographics, admission vital signs, emergency department disposition, length of stay, and injury severity scores (ISS). Admission to the ICU, need for emergency operation, length of stay, and death were noted. Emergency medical service staff were queried to determine which standard triage criteria (STC) were fulfilled. RESULTS: The mean ALAC was 3.11 mmol/L (SD 3.45, 95% confidence interval [CI] 2.67 to 3.55) and mean VLAC was 3.43 mmol/L (SD 3.41, 95% CI 2.96 to 3.90). There was no significant difference between ALAC and VLAC. The correlation between ALAC and VLAC was 0.94 (95% CI 0.94 to 0.96, p = 0.0001). An elevated VLAC predicted moderate to severe injury and there was a significant association between an increased lactate and maximum Abbreviated Injury Score (AIS) of 4 and 5 (ANOVA, F = 8.26, p < 0.001). Patients with VLAC > or =2 mmol/L had significantly increased relative risks of ISS > or = 13, death, admission to the ICU, and length of stay > 2 days. In comparison with STC, a VLAC > or = 2 mmol/L decreased undertriage in patients with ISS > or = 13 by one half (11% versus 24%) for patients with ISS > or = 13 and decreased over-triage by 28% (46% versus 64%). These data were most pronounced for patients injured in motor vehicle collisions. CONCLUSIONS: VLAC is an excellent approximation for ALAC. A VLAC > or = 2 mmol/L appears to predict an ISS > or = 13, the need for ICU resources, and prolonged hospital stays. VLAC was significantly better than STC in all patients and was most useful in victims of blunt trauma, especially motor vehicle collisions.

Effects of hypoxia on granulocytic-monocytic progenitors in rats. Role of bone marrow stroma.

Hemorrhagic shock leads to hypoxia and is associated with bone marrow (BM) failure. Hemorrhagic shock is also a predisposing factor in immune dysregulation. Since the BM is the major organ of immune cells in the adult, its failure following hemorrhagic shock may explain the increased susceptibility to infection. The in vitro evidence indicates that hypoxia mediates altered functions in BM stroma. Since similar hematopoietic alterations are reported in hypoxia and hemorrhagic shock, hypoxia alone could be a representative model to study BM responses during hemorrhagic shock. In this study, we use an animal model to dissect the hematopoietic effects of hypoxia. We subjected rats to hypoxia, and at days 1 and 5 post-hypoxia we determined the numbers of granulocytic-monocytic progenitors (CFU-GM) in the BM. We found significant increase (P < 0.05) in CFU-GM at day 1 and a downward trend by day 5. Enhanced BM cellularity could not explain the increase in CFU-GM by day 1. BM stromal cells mediated most of the stimulatory effects by hypoxia. CFU-GM was inversely proportional to bioactive TGF-beta and directly proportional to IL-1. Compared to normoxic rats, IL-6 production was suppressed in BM cells from hypoxic rats. The results show that hypoxia alone initiate a stimulatory response in CFU-GM progenitors. These effects are at least partially mediated through the BM stroma. In the absence of a second insult, CFU-GM reverts to baseline. The data also suggest that hypoxia mediates complex responses that include cytokine production. These results add to the current understanding of hematopoietic responses by hypoxia and adds to the mechanisms of immune dysfunctions following hemorrhagic shock.

Acute pancreatitis complicating anterior lumbar interbody fusion.

Postoperative pancreatitis may occur following surgery in regions remote from the pancreas and the biliary tree. Though uncommon, it carries a high mortality rate. Pancreatitis complicating spinal surgery is extremely rare. This report describes a case of acute pancreatitis following an anterior lumbar interbody fusion and discusses the possible mechanisms of pancreatic cellular injury.

Major trauma enhances store-operated calcium influx in human neutrophils.

PURPOSE: Chemotaxins from inflammatory sites prime or activate neutrophils (PMN) by using cytosolic calcium ([Ca2+]i) fluxes as second messengers. [Ca2+]i can be mobilized rapidly by receptor-mediated entry or store-release, or more slowly by store-operated calcium influx (SOCI). We studied [Ca2+]i mobilization by chemotaxins and how trauma impacts the calcium entry mechanisms used by chemotaxins. METHODS: [Ca2+]i flux was studied by spectrofluorometry. The contributions of early and late [Ca2+]i currents to net calcium flux were compared after stimulation by more potent (fMLP, C5a, PAF) or less potent (IL-8, GRO-alpha, and LTB4) agonists. Store operated [Ca2+]i mobilization was reflected by the ratio of area under the [Ca2+]i efflux curve to peak [Ca2+]i (efflux curve). PMN from trauma patients (ISS > 25) and pair-matched volunteer (n = 7 pairs) were then primed and stimulated with thapsigargin to compare cell calcium stores and SOCI. RESULTS: Late [Ca2+]i mobilization made more important contributions to fMLP, PAF, and C5a signals than to IL-8, GRO-alpha, or LTB4 (p < 0.01 all comparisons). Calcium stores and store release were only marginally lower after injury (p = not significant), but trauma PMN showed far higher [Ca2+]i influx after thapsigargin (p = 0.007), and greater net SOCI (p = 0.034). CONCLUSIONS: SOCI may play an important role in PMN activation, and trauma increases PMN SOCI. Prolonged elevations of [Ca2+]i due to enhanced SOCI may alter stimulus-response coupling to chemotaxins and contribute to PMN dysfunction after injury.

Taking care of the "good guys:" a trauma center-based model of medical support for tactical law enforcement.

The potential need for rapid medical intervention and access to a trauma center after major injury is crucial to the safety and success of SWAT team operations. This manuscript describes the genesis and development of a unique model for which advanced medical care is rendered by trained health care professionals within a regional trauma system in the support of a SWAT team. The model was developed jointly by the Newark, New Jersey, Division of the Federal Bureau of Investigation and The New Jersey Trauma Center-University Hospital, an academic, urban Level I trauma center. After the signing of a Memorandum of Understanding between the two agencies in 1995, the program became operational. The medical team is composed of physicians, nurses, and paramedics. Since inception, the medical team has provided medical support for 33 tactical missions and 99 training days. Ten patients were treated: 7 agents (syncope, fractured foot, blunt head/neck trauma, lacerations), 2 bystanders (chest pain, asthma), and 1 suspect (chest pain). The advantages of the Newark model in contrast to other programs of tactical medical support, are the operational activities of the team and the cost of the program was outlined.

CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils.

Neutrophil (PMN) priming and subsequent responses to the IL-8 presented on pulmonary endothelial surfaces may be crucial determinants of the development of adult respiratory distress syndrome after injury. Elevated plasma ELR+ C-X-C chemokine (CXC) levels might contribute to PMN priming after trauma, but the role of CXCs in priming circulating PMNs is unstudied. We evaluated the interactions of IL-8 and GRO-alpha in priming human PMN calcium fluxes [Ca2+]i within circulatory environments. At physiologic concentrations, GRO-alpha primes PMN for IL-8 mediated [Ca2+]i mobilization, whereas IL-8 abolishes GRO-alpha responses. Repeated GRO-alpha exposures further enhance IL-8 responses. PMN priming for IL-8 responses in normal plasma was CXCR2 dependent. CXCR2 was more responsive than CXCR1 to low levels of IL-8, together suggesting that CXCR2 is the important CXC receptor at circulating (i.e., low) agonist concentrations. CXCR1 stimulation down-regulated CXCR2 surface expression, whereas CXCR2 stimulation upregulated CXCR1 expression. GRO-alpha/ CXCR2 signaling enhanced post-receptor IL-8 initiated PMN [Ca2+]i influx as well as efflux. Sufficient stimulation of the CXCR1 terminated this cooperative relationship by downregulating surface expression of CXCR2. This study is the first to report that at physiologic concentrations, C-X-C chemokines can act on circulating human PMNs as an integrated system where CXCR2 agonists, rather than cross-desensitizing CXCR1, act to enhance signaling of IL-8 at CXCR1 both by receptor and post-receptor mechanisms. Such CXCR2 mediated priming of CXCR1/ IL-8 interaction may enhance PMN attack on the lung after injury.