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C J Hauser

Publications and source records attributed to C J Hauser.

At least 19 recordsLinked to original sources
PubMed2000

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.

Adult↗
PubMed1999

Role of granulocyte-macrophage colony-stimulating factor and its receptor in the genesis of acute respiratory distress syndrome through an effect on neutrophil apoptosis.

HYPOTHESIS: That granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor modulate the suppression of apoptosis (Ao) of normal neutrophils incubated in the plasma of patients with postraumatic acute respiratory distress syndrome (ARDS). DESIGN: Experimental study using cultured human neutrophils. SETTING: University hospital, level I trauma center. PARTICIPANTS: Plasma was obtained from 14 patients with early, fulminant posttraumatic ARDS (mean Injury Severity Score, 22). All samples were drawn within 24 hours after injury. Plasma was also taken from up to 21 healthy control subjects. These volunteers were also used as sources of polymorphonuclear leukocytes (PMNs). MAIN OUTCOME MEASURES: (1) Effect of early, fulminant ARDS and normal plasma on spontaneous Ao and GM-CSF receptor expression in PMNs in vitro. (2) Effect of ligation of either GM-CSF or its receptor with a neutralizing monoclonal antibody (mAb) on PMN Ao in ARDS and normal plasma. (3) Correlation of extracellular GM-CSF concentration with rate of PMN Ao. (4) Levels of GM-CSF in ARDS and normal plasma and in culture supernatant of normal PMNs incubated in early, fulminant ARDS and normal plasma. RESULTS: Plasma from patients with ARDS enhanced PMN viability at 24 hours (data are given as mean +/- SEM) 52% +/- 3% control vs 60% +/- 3% ARDS, P<.05). Binding of the GM-CSF receptor with a neutralizing mAb significantly reduced PMN viability in ARDS plasma, but not in normal plasma (60% +/- 3% ARDS vs 53% +/- 3% ARDS + mAb, P<.05). Ligation of GM-CSF with mAb had no significant effect on PMN viability in either plasma. Only 1% of PMNs expressed detectable levels of the GM-CSF receptor when incubated for 24 hours in either ARDS or normal plasma. The GM-CSF levels were undetectable (>7 pg/mL) in both ARDS and normal plasma and in culture supernatants taken after 24 hours of incubation in both plasma types. Levels of GM-CSF ranging from 0 to 50000 pg/mL had no effect on PMN Ao in plasma-free medium. CONCLUSIONS: The antiapoptotic effect of ARDS plasma appears to be mediated by the GM-CSF receptor. This effect occurs at both low levels of plasma GM-CSF and surface expression of its PMN receptor. Ligation of GM-CSF had no effect of PMN Ao, suggesting that Ao is triggered by Fc portion-mediated receptor cross-linking. These results provide the theoretical basis for alphaGM-CSF receptor mAb therapy as a novel modality of treatment for ARDS.

Acute Disease↗
PubMed1999

Prospective randomized trial of thoracostomy removal algorithms.

INTRODUCTION: The preferred chest tube (CT) removal algorithm has not yet been established. The purpose of this study was to determine which technique, water seal or suction, allowed for shorter CT duration. In addition, the recurrent pneumothorax (PTX) rate, the need for CT reinsertion, and the total number of chest x-ray films (CXR) were determined. METHODS: Prospective randomized trial of 205 trauma patients, older than 15 years of age, requiring tube thoracostomy for blunt and penetrating trauma. Patients requiring mechanical ventilation more than 24 hours were excluded from the study. Informed consent was obtained from all patients. Chest tubes were randomized for removal when output was less than 150 mL/24 hours, CXR revealed no significant PTX, and no air leak was present. Patients in the water seal group were disconnected from low wall suction and a CXR was obtained 6 to 8 hours later. Chest tubes in the no water seal group were disconnected from wall suction and pulled immediately. All tubes were removed by using standard protocol with patients at maximal inspiratory effort. A follow-up CXR was obtained after removal. RESULTS: Of the 205 patients, 93 patients (45 %) were randomized to the water seal group and 112 patients (54%) to the no water seal group. Four patients in the water seal group developed a PTX before CT removal and were considered treatment failures. After CT removal, repeat PTX was seen in 13 patients in the water seal group and in 9 patients in the no water seal group. However, seven patients in the no water seal group required CT reinsertion compared with one in the water seal group (p<0.05). Average number of CXR in the water seal group was 6.5 compared with 5.5 radiographs in the no water seal group. There was no difference in chest tube duration or hospital length of stay between groups for either all patients or only those patients with isolated chest injuries. Patients who required another CT had a hospital length of stay twice that of patients who did not. CONCLUSIONS: It is possible that patients in the no water seal group did not have sufficient time for a possible PTX to evolve, which resulted in a larger and more significant PTX requiring another CT. Although there was no difference in chest tube duration between the no water seal and water seal groups, a short trial of water seal appears to allow occult air leaks to become clinically apparent and reduces the need for another CT.

Adult↗
PubMed1999

Priming of neutrophil [Ca2+]i signaling and oxidative burst by human fracture fluids.

BACKGROUND: Patients with major fracture/soft-tissue injuries are at risk for adult respiratory distress syndrome after secondary infection. Fracture fluids (FF) are rich in neutrophil (PMN) -specific chemokines such as interleukin-8. PMN respond to both interleukin-8 and bacterial stimuli with calcium ([Ca2+]i) fluxes, which can initiate respiratory burst (RB). We hypothesize that small amounts of FF entering the circulation could exaggerate PMN [Ca2+]i and RB responses, potentially increasing the risk of adult respiratory distress syndrome. METHODS: FF were obtained from 10 patients at open fixation of the femur 2 to 5 days postinjury. Volunteer PMN were isolated and loaded with fura dye. PMN were preincubated either in 30% autologous plasma (AP)/70% buffer, or in 5% FF/25% AP/70% buffer. Cells were resuspended in buffer with 1,2,3-dihydrorhodamine and stimulated with low-dose n-formyl-methionyl-leucyl-phenylalanine (fMLP). [Ca2+]i was assayed by fura fluorescence at 505 nm after excitation at 340/380 nm. RB was assessed by 1,2,3-dihydrorhodamine fluorescence at 530 nm after 488 nm excitation. RESULTS: PMN basal [Ca2+]i was higher after FF incubation than AP incubation (94+/-12 vs. 61+/-9 nmol/L, p = 0.0002). Peak [Ca2+]i response to fMLP was 475+/-47 nmol/L after FF but only 356+/-22 nmol/L after AP (p = 0.01). Two hundred seconds after fMLP, [Ca2+]i remained higher after FF (172+/-17 vs. 145+/-9 nmol/L, p = 0.04). Basal RB was slightly higher after FF than AP (13.4+/-0.3 vs. 11.3+/-0.3 units, p = 0.051) as was the maximal rate of extracellular oxidant release (1.10+/-0.17 vs. 0.76+/-0.16 units/s, p = 0.004) and total oxidant production (42.5+/-0.8 vs. 31.7+/-0.8 units, p = 0.006). CONCLUSION: Small amounts of FF in plasma can exaggerate PMN [Ca2+]i flux and RB responses to subsequent bacterial stimuli. These findings are consistent with the hypothesis that release of FF into the circulation primes PMN and, thus, may predispose to adult respiratory distress syndrome. Such PMN priming events might have important implications for both the operative and medical management of patients with major fractures.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

Integrated stimulation by CXC chemokines enhances PMN [Ca2+]i signaling in trauma and adult respiratory distress syndrome.

BACKGROUND: Trauma and adult respiratory distress syndrome (ARDS) are associated with increased CXC chemokine (CXC) activity. CXCs such as interleukin (IL)-8 activate polymorphonuclear neutrophils (PMNs) in the lung by means of calcium signals ([Ca2+]i). We studied CXC effects on PMN [Ca2+]i in ARDS and trauma. METHODS: Isolated PMNs were loaded with Fura-2 dye. Normal PMNs were incubated in ARDS plasma or volunteer plasma, with or without blocking antibodies to IL-8, growth-related oncogene alpha (GRO-alpha), or both (n = 6 pairs), and then stimulated with 1 to 10 nmol/L IL-8. PMNs from trauma patients or volunteers (n = 10 pairs) were stimulated with GRO-alpha, or with sequential GRO-alpha/IL-8. [Ca2+]i was measured with spectrofluorometry. RESULTS: [Ca2+]i responses to IL-8 were higher after being incubated in ARDS plasma than in volunteer plasma (251 +/- 33 vs 218 +/- 33 nmol/L, P = .03). Blockade of GRO-alpha or IL-8 reversed ARDS plasma effects. After GRO-alpha/IL-8, PMNs from trauma patients demonstrated more Ca2+ store release than did PMNs from volunteers (235 +/- 13 vs 170 +/- 10 nmol/L, P < .01). Conversely, PMNs from trauma patients lost receptor-operated Ca2+ influex to GRO-alpha. CONCLUSIONS: In traumatic ARDS, plasma CXCs prime PMNs for higher [Ca2+]i flux, making PMN activation more likely. IL-8 and GRO-alpha interact to modulate these PMN [Ca2+]i responses.

Adult↗
PubMed1998

Role of interleukin 8 in the genesis of acute respiratory distress syndrome through an effect on neutrophil apoptosis.

OBJECTIVE: To evaluate the role of interleukin 8 (IL-8) in the regulation of neutrophil (PMN) apoptosis in normal plasma and plasma from patients with early, fulminant acute respiratory distress syndrome (ARDS). DESIGN: Experimental study using cultured human PMNs. SETTING: University hospital, level I trauma center. PARTICIPANTS: Plasma was obtained from 6 patients with early, fulminant posttraumatic ARDS (mean Injury Severity Score, 26). All samples were drawn within 24 hours after injury. Plasma was also taken from 13 healthy control subjects. These controls were also used as sources of PMNs. MAIN OUTCOME MEASURES: Effect of early, fulminant ARDS and normal plasma on spontaneous apoptosis, CD16, and CD11-b expression in PMNs in vitro; levels of IL-8 in plasma; correlation of extracellular IL-8 concentration with rate of PMN apoptosis; and effect of IL-8 blockade on PMN apoptosis, CD16, and CD11-b expression in ARDS and normal plasma. RESULTS: Plasma from patients with early, fulminant ARDS inhibited spontaneous PMN apoptosis at 24 hours (35%+/-5% vs 54%+/-5%; P=.01). Neither CD16 nor CD1l-b differed significantly between the 2 groups. The mean plasma level of IL-8 in patients with early, fulminant ARDS was 359+/-161 pg/mL vs 3.0+/-0.4 pg/mL in healthy controls (P<.05). Interleukin 8 inhibited apoptosis in plasma-free medium at low doses (1-50 pg/mL) but had no significant effect at higher doses (100-5000 pg/mL) (P<.05). Interleukin 8 blockade with monoclonal antibody suppressed apoptosis in normal plasma (28%+/-5% with monoclonal antibody vs 51%+/-5% without monoclonal antibody; P=.008) but not in plasma from patients with early, fulminant ARDS (29%+/-5% with monoclonal antibody vs 34%+/-6% without monoclonal antibody; P=.67). It had no effect on CD16 or CD11-b expression in either plasma. CONCLUSIONS: Plasma from patients with early, fulminant ARDS contains soluble factors that inhibit PMN apoptosis in vitro. Low levels of IL-8 inhibit PMN apoptosis in normal plasma. Although plasma levels of IL-8 are markedly elevated in early, fulminant ARDS, IL-8 is not directly responsible for the antiapoptotic effect of plasma from patients with early, fulminant ARDS.

Apoptosis↗
PubMed1998

Effect of hypoxia on the hematopoietic and immune modulator preprotachykinin-I.

OBJECTIVES: To determine the effect of hypoxia on bone marrow mononuclear cells (BMMCs) and their ability to proliferate into granulocyte-macrophage colony-forming units (CFU-GMs) and erythroid burst-forming units (BFU-Es) and to determine the role of the neuroimmune and hematopoietic mediator, substance P. DESIGN: Controlled in vitro study. SETTING: University research laboratory. MATERIALS: Bone marrow aspirates were obtained from the posterior iliac crests of healthy volunteers after obtaining informed consent. INTERVENTIONS: The BMMCs were divided into the following groups: (1) normoxia, (2) two hours of hypoxia, and (3) six hours of hypoxia. Additional BMMCs were purified before the period of hypoxia, while others were incubated with neurokinin (NK) receptor antagonists. In other experiments, bone marrow stroma was grown to confluence and randomized to the following groups: (1) normoxia, (2) hypoxia, (3) normoxia and interleukin (IL) 1, and (4) hypoxia and IL-1. All groups were cultured for 2, 6, 12, or 24 hours. MAIN OUTCOME MEASURES: The formation of CFU-GMs and BFU-Es was measured after 10 to 14 days of incubation of the BMMCs. The messenger RNA of the preprotachykinin-I (PPT-I) gene and the NK-1 and NK-2 receptors was detected by using semiquantitative reverse transcriptase-polymerase chain reaction or Northern blot analysis on bone marrow stroma. The immunoreactivity of substance P in bone marrow stroma was measured by competitive enzyme-linked immunosorbent assay. RESULTS: Hypoxia resulted in a 110% increase in the number of CFU-GMs and a 78% increase in the number of BFU-E colonies at 6 hours (both P<.05). Elimination of the stromal elements by purification abrogated the increase in colony formation to nonhypoxic levels. Hypoxia induced PPT-I gene expression at 24 hours; however, no PPT-I expression was found in the hypoxic group incubated with IL-1. The receptor, NK-1, was found to be equal in both hypoxic groups; NK-2 was found to have a 4-fold increase in the hypoxia and IL-1 group over the hypoxia alone group and normoxia and IL-1 group. The levels of substance P immunoreactivity were found to be similar in all groups. Incubation of BMMCs with NK receptor antagonists to NK-1 alone or NK-1 and NK-2 decreased the number of CFU-GM and BFU-E colonies similar to the level in controls. CONCLUSIONS: These results indicate that hypoxia has a role in the proliferation and control of CFU-GMs and BFU-Es. This control seems to be mediated through the bone marrow stroma and modulated by NK receptors and induction of PPT-I. The neuropeptide, substance P, probably has a role but is clearly not the only mediator involved.

Cell Hypoxia↗
PubMed1998

Chemokine stimulation of human neutrophil [Ca2+]i signaling in biologic environments.

Clinical neutrophil (PMN) priming is the net result of multiple stimuli, with intracellular calcium ([Ca2+]i) being a key second messenger for PMN agonists such as the chemokines. Thus, [Ca2+]i measurement may be a robust tool for the assessment of global PMN activation. [Ca2+]i is difficult to measure in complex biologic environments, however, so data in this area are limited. We therefore developed an in vitro system to measure the effects of chemokines on PMN [Ca2+]i. PMN were isolated from volunteer blood. PMN [Ca2+]i responses to interleukin (IL)-8 and Growth-Related Oncogene (GRO)-alpha were studied by fura-2-acetoxymethyl ester fluorescence with or without reincubation in autologous plasma just prior to study. The effects of IL-8 and GRO-alpha on PMN [Ca2+]i at ascending doses, with or without plasma reincubation, given sequentially and in the presence or absence of extracellular calcium, were studied. PMN basal [Ca2+]i was increased by plasma, as were low-dose priming and higher-dose spike responses to IL-8. GRO-alpha caused a more pronounced priming of PMN [Ca2+]i than IL-8 at low doses, although significantly lower peak responses were observed with GRO-alpha than IL-8 at higher doses. Plasma suppressed both priming and spike responses to GRO-alpha. When given serially at clinically relevant agonist doses, GRO-alpha was permissive of IL-8 signaling, whereas IL-8 blocked GRO-alpha signaling. IL-8 generates high [Ca2+]i spikes using intracellular calcium stores only. GRO-alpha produces lower [Ca2+]i spikes despite using both intra- and extracellular stores. Plasma preincubation has profound effects on PMN [Ca2+]i responses to chemokines. These can be measured accurately, as described. In clinically relevant environments, IL-8 and GRO-alpha interact in a regulatory fashion. GRO-alpha may act as a priming agent, with IL-8 activating PMN functions requiring high [Ca2+]i. This cross-cooperation is probably terminated by IL-8 regulation of GRO-alpha activity at the C-X-C chemokine receptor 2.

Calcium↗
PubMed1998

Mechanism of suppression of natural killer cell activity in trauma patients.

Trauma patients develop a severe immunosuppression that includes suppression of natural killer (NK) cell activity although numbers of NK cells are not reduced. The mechanism of suppression of NK cell activity after major trauma is not known. The aim of the present study was to investigate the in vitro effect of plasma samples from trauma patients (TP) on the cytotoxic activity of normal NK cells. Buffycoat mononuclear cells (5x10(5)/well) were preincubated with either TP or plasma samples from age and sex matched healthy controls (CP) for 0, 16 or 40 h. These effector cells were then cultured with 51Cr labeled K-562 cells (2x10(4)/well) for 4 h at 37 degrees C and % lysis was calculated. No significant differences in % lysis between CP and TP were found with 0 or 16 h preincubation, however 40 h preincubation with TP severely suppressed NK cell function (p=0.003) as compared to preincubation with CP for the same period. Addition of neutralizing anti-IL-4, anti-TGF-beta1, or anti-IL-10 antibodies did not reverse the NK cell suppression. There was a partial reversal of NK cell suppression by catalase but not by SOD or L-NMMA. Removal of monocytes from buffycoat mononuclear cells also significantly reversed the NK cell suppression. These data suggest that suppression of NK cell activity in trauma patients may be an accessory cell dependent phenomenon and may partially depend on production of reactive oxygen metabolites (ROM).

Catalase↗
PubMed1997

Suppression of natural killer cell activity in patients with fracture/soft tissue injury.

BACKGROUND: Natural killer cells (NKCs) participate in "innate" cell-mediated immunity. Fracture/soft tissue injuries are cytokine rich and may influence cell-mediated immunity. OBJECTIVE: To study the effects of fracture cytokines on NKC function. DESIGN: A case-control study. SETTING: A level I trauma center and laboratory in a university medical center. PARTICIPANTS: Patients requiring open fracture fixation and healthy volunteers. INTERVENTIONS: Fracture supernatants and peripheral plasma were collected during open fracture fixation. Volunteer mononuclear cells were used as effector (NKC) sources. Mononuclear cells were preincubated with fracture supernatants, paired peripheral plasma, or normal plasma under various conditions. MAIN OUTCOME MEASURES: Natural killer cell lysis of K562 target cells was assessed by chromium 51 release. RESULTS: Fracture supernatants suppressed NKC function more rapidly than peripheral plasma. Fracture supernatants from 1 to 4 days after injury were most suppressive. Inactivation of complement and reactive oxygen species failed to restore lysis. Neutralizing antibodies to interleukin 4 and interleukin 10 further suppressed lysis. Antibodies to transforming growth factor beta1 failed to restore lysis. The addition of interferon gamma did not restore lysis but the addition of interleukin 12 did. CONCLUSIONS: Fracture supernatants and peripheral plasma from patients with fractures suppress NKCs. The responsible mediators may be concentrated in fracture/soft tissue injuries. Responses to manipulation of the cytokine environment suggest that fracture cytokines may impair cooperation between NKCs and accessory cells.

Adult↗
PubMed1997

Psychopathologic risk factors for intentional and nonintentional injury.

OBJECTIVE: Trauma has a high rate of recurrence, suggesting that some people are more injury-prone than others. This study was performed to evaluate some of the psychological and social factors that might influence the likelihood of traumatic injury. METHODS: A case-control study was conducted to evaluate the relationship between selected psychosocial factors and traumatic injury. At a Level I trauma center, victims of intentional trauma (excluding attempted suicide), victims of nonintentional trauma, and patients undergoing elective surgery were interviewed by a person blinded to the purposes of the study. They were given an intelligence test and underwent a structured interview, yielding psychiatric diagnostic categories established in the third edition of the Diagnostic and Statistical Manual of Mental Disorders, Revised (DSM-III-R). RESULTS: Trauma patients were younger than elective surgery patients (p < 0.01) and were more likely to be men (p < 0.01). Victims of intentional injury had a higher probability of alcohol use (p < 0.01) and admitted illicit drug use (p < 0.001) than either nonintentional injury victims or elective surgery patients. Victims of intentional injury were more likely to be unemployed than those in the other two groups (p < 0.02), whereas elective surgery patients were more likely to be retired (p < 0.05) or to be disabled (p < 0.0001). The average intelligence score was slightly above the median in the nonintentional trauma group and in the control group (55th percentile and 54th percentile, respectively), compared with a mean intelligence score equivalent to the 35th percentile in the victims of intentional trauma (p < 0.001). Thirty percent of elective surgery patients met diagnostic criteria for at least one category of psychopathology, compared with 50% of nonintentional trauma patients, and 63% of intentional trauma patients (p < 0.01, trauma vs. elective surgery). Logistic regression analysis identified six variables that were independently associated with an increased tendency to be a victim of trauma: younger age, lower intelligence, antisocial personality, mental retardation, depression, and low income. CONCLUSIONS: Victims of trauma, both nonintentional, and especially intentional, have a high incidence of psychopathology. Victims of intentional trauma have significantly lower intelligence scores than either nonintentional injury or elective surgery patients. The high incidence of unemployment, alcohol abuse, and illicit drug use in victims of intentional injury might provide several opportunities for trauma prevention programs. Underlying psychological disorders will have to be addressed to reduce the likelihood of becoming a victim of trauma.

Accident Proneness↗
PubMed1997

The immune microenvironment of human fracture/soft-tissue hematomas and its relationship to systemic immunity.

The immune environment of human soft-tissue injury is unstudied. We studied fracture soft-tissue hematomas (FxSTH) in 56 patients with high-energy bony fractures. FxSTH serum and mononuclear cells (MNC) as well as fracture patient plasma and blood MNC were studied. Twenty healthy controls donated plasma and MNC. Soluble tumor necrosis factor (TNF)-alpha, interleukin (IL-1 beta, IL-2, 6, 8, 10, 12, and interferon-gamma were studied by enzyme linked immunosorbent assay. Cells were studied by flow cytometry after cell-membrane stains for CD-14, TNF-alpha (mTNF), and human leukocyte antigen-DR, or intracellular stains for TNF (icTNF) and IL-10. Thirty-six patients with Injury Severity Score < 15 were analyzed further to evaluate the effects of isolated fracture on systemic immunity. Cytokines were rarely detectable in control plasma. TNF-alpha, IL-1 beta, IL-2, and interferon-gamma were rarely found in FxSTH serum or fracture patient plasma. All FxSTH sera were rich in IL-6, peaking before 48 hours (12,538 +/- 4,153 vs. 3,494 +/- 909 pg/mL, p = 0.02, U test). In Injury Severity Score < 15, IL-6 was not detectable in most early fracture patient plasma, but rose after 48 hours (p = 0.028). FxSTH serum IL-8 peaked after 48 hours (440 +/- 289 vs. 4,542 +/- 1,219 pg/mL, p = 0.006) and circulating IL-8 appeared after 72 hours. IL-6 and IL-8 showed gradients from FxSTH serum to paired PtS (p < 0.05, Wilcoxon). IL-10 was abundant (884 +/- 229 pg/mL) in FxSTH serum < 24 hours old. FxSTH serum IL-12 peaked late (3,323 +/- 799 pg/mL, day 4-7) then fell (p < 0.001, analysis of variance). Only IL-12 was higher in fracture patient plasma (1,279 +/- 602 pg/mL) than FxSTH serum (591 +/- 327 pg/mL) during the first 48 hours (p = 0.032, U test). On flow cytometry, control monocytes expressed 201 +/- 31 mTNF sites/cell, but icTNF was absent. mTNF was up-regulated after injury more in FxSTH monocytes (3,202 +/- 870 sites/cell) than peripheral blood monocytes (584 +/- 186 sites/cell) (p < 0.05 vs. peripheral blood monocytes by Wilcoxon, p < 0.001 vs. control monocytes by U test). Intracellular IL-10 was abundant in all MNC, but varied widely after injury. Fracture and peripheral blood monocytes expressed far less human leukocyte antigen-DR than control monocytes. Fractures create an inflammatory local environment. Proximal mediators are cell-associated and relatively confined to the wound, but soluble IL-6, IL-8, and IL-10 are abundant and probably exported. Systemic MNC have complex responses to local injuries. These may reflect the combined impact of multiple soluble cytokines initially generated within the wound. FxSTH appear to be a potentially important source of immunomodulatory cytokines in trauma.

Adolescent↗
PubMed1996

Laparoscopy in trauma.

Laparoscopy is a nearly century-old technique that has experienced a resurgence of interest from surgeons since the development of technology that has broadened its applications. Although laparoscopy has been used to evaluate patients with possible abdominal trauma, its use for this purpose is limited by the availability of other diagnostic procedures that may be more suitable for particular circumstances and are more accurate for certain injuries. Laparoscopy is contraindicated in patients who are hypovolemic or hemodynamically unstable and should not be performed in patients with clear indications for celiotomy. It may not be appropriate for patients with cardiac dysfunction, nor for those with significant head injuries who are at risk for intracranial hypertension. Its best applications may be in stable patients with stab wounds or those with tangential gunshot wounds of the abdomen. The likelihood of missing hollow visceral injuries depends upon the indications for conversion to celiotomy. If peritoneal violation or the presence of a small amount of blood in the peritoneal cavity is used as an indication for celiotomy, then the missed injury rate will be low but the unnecessary celiotomy rate will be diminished only slightly compared with a policy of mandatory celiotomy. Excessive enthusiasm for laparoscopy in trauma might result in its use when other diagnostic measures or simple observation are more appropriate. The desire to perform a procedure can be compelling, especially in circumstances in which the general surgeon would not operate upon a patient but simply provide postoperative care after other surgeons have operated. The use of laparoscopy for these purposes can only be condemned, as it increases the costs and risks of care without improving the outcome. The role of laparoscopy in trauma is evolving, and further research into its diagnostic role and therapeutic applications is clearly needed.

Abdomen↗
PubMed1996

Abbreviated Injury Scale does not reflect the added morbidity of multiple lower extremity fractures.

OBJECTIVES: To determine if patients with multiple lower extremity fractures have worse outcomes than do patients with isolated femur fractures, and to determine if the Abbreviated Injury Scale (AIS) should distinguish between single and multiple lower extremity fractures. DESIGN: A retrospective study. MATERIALS AND METHODS: All blunt trauma patients at least 15 years of age treated at a level 1 trauma center from January 1990 through December 1993. Three groups of patients were selected. Group 1 included 50 patients whose only significant injury was a diaphyseal femur fracture. They had no other long bone fractures, minimal injuries to other body areas, and an Injury Severity Score (ISS) < or = 14. Group 2 was consisted of 29 patients with a femur fracture, at least one other diaphyseal lower extremity fracture, and also an ISS < or = 14. Group 3 consisted of 23 patients who had fracture patterns similar to those of group 2, but also had more severe nonextremity injuries (ISS > or = 15). Hospital morbidity and mortality rates were compared with t tests or chi-square analysis. Type 1 error probability was established at p < 0.05. MEASUREMENTS AND MAIN RESULTS: Compared with patients in group 1, patients in group 2 had an identical ISS (10.1 vs. 10.6, respectively), but had higher transfusion requirements (0.3 vs. 3.9 units), more days in the intensive care unit (ICU) (0.02 vs. 1.4), a higher incidence of adult respiratory distress syndrome (ARDS) (0 vs. 14%), longer hospital stays (6.0 vs. 14.8 days), greater disability at discharge (disability score 2.2 vs. 3.2), and a higher mortality rate (0 vs. 3.4%; p < 0.05 all variables). Patients in group 3 had worse outcomes than the other two groups: ISS = 30.1; transfusions = 11.9 units; ICU days = 9.1; ARDS incidence = 26%; hospital days = 29.9; disability score = 3.9; mortality = 26% (p < 0.05). CONCLUSIONS: Although AIS and ISS appropriately reflect the impact of extraskeletal injuries in patients with femur fractures, they do not adequately reflect the increased morbidity associated with multiple lower extremity fractures. The AIS-Extremity Score may need to be upgraded for multiple long bone fractures of the lower extremities.

Abbreviated Injury Scale↗
PubMed1996

Production of interleukin-10 in human fracture soft-tissue hematomas.

Clinical trauma suppresses immunity and experimental wound fluids have been shown to be immunosuppressive. To ascertain whether human wounds contain immunosuppressive cytokines, we assayed serum from fracture/soft-tissue hematomas (FSTH) of 22 patients for interleukin (IL)-10, transforming growth factor (TGF)-beta 1, and IL-4. Results were correlated to concurrent plasma cytokine concentrations in the same patients and in volunteer plasma. IL-10 was present in high concentration (1376 +/- 539 pg/mL) in all (7/7) FSTH < 24 h old. In FSTH > 24 h old, IL-10 was found intermittently and at lower levels (239 +/- 106 pg/mL, p = .011 vs. FSTH < 24 h old). IL-10 was rarely detectable in fracture patient plasma and never detectable (< 20 pg/mL) in normal plasma. No significant variations of IL-4 or total TGF-beta 1 were found in FSTH or plasma. FSTH are significant potential sources of IL-10 activity in trauma patients, which may be overlooked when only plasma is assayed. The potential for a relationship between cytokines found locally at sites of injury and clinical immune modulation in trauma requires further study.

Adult↗