Biomedical subjects

V M Peterson

Publications and source records attributed to V M Peterson.

At least 19 recordsLinked to original sources

PubMed1997

Base deficit after major trauma directly relates to neutrophil CD11b expression: a proposed mechanism of shock-induced organ injury.

OBJECTIVE: To determine whether expression of neutrophil integrin receptors is related to the degree of post-traumatic shock. DESIGN: Data were collected prospectively on patients with major trauma admitted to the surgical intensive care unit. SETTING: Denver General Hospital, Colorado. PATIENTS AND PARTICIPANTS: 17 severely injured adults. MEASUREMENTS AND RESULTS: The mean fluorescence intensity and per cent positive of neutrophil integrin receptors CD11 b, CD18 and CD11 a, and systolic blood pressure, blood transfusion, lactate and base deficit as indices of shock. CD11 b expression on circulating neutrophils was increased 6 and 12 h after trauma. After correcting for the other shock indices, base deficit predicted CD11 b expression at 12 h. CD11 b expression was negatively correlated with the circulating neutrophil count. CONCLUSIONS: The degree of metabolic acidosis after trauma correlates directly with CD11 b receptor expression on circulating neutrophils. This relation may be the mechanism whereby post-traumatic shock results in neutrophil sequestration and neutrophil-mediated organ injury and failure.

Acidosis↗

PubMed1996

Neutrophils from patients after burn injury express a deficiency of the oxidase components p47-phox and p67-phox.

Infection is a major cause of morbidity and mortality in patients after thermal injury. This predisposition to infections is related, in part, to abnormal polymorphonuclear leukocyte (PMN) function and a diminished respiratory burst. To evaluate the biochemical basis for the defective respiratory burst after major burns, the status of the oxidase enzyme system and its components was investigated. PMNs were isolated from 24 patients with 12% to 62% burns. Oxidase activity of intact PMNs, measured as superoxide anion (O2-) generation or oxygen consumption, was decreased in burn compared with healthy controls. Subcellular fractions from patient PMNs generated less O2- in the sodium dodecyl sulfate cell-free system, and this was related to a diminished contribution by cytosol but not by plasma membrane. Subsequently, cytosol was separated with CM-Sepharose, yielding two fractions; one contained the p47-phox and p67-phox (47/67 mix) and the other contained the remaining cytosolic components (run through [RT]). Although the contribution to oxidase activity made by RT from patient cytosol was similar to that of control, the activity of p47/67 mix from PMNs of burn patients was deficient. Quantitative assays using an immunoautoradiographic technique showed a consistent, but significant decrease in both p47-phox and p67-phox. The addition of purified or human recombinant p47-phox but not p67-phox corrected the diminished oxidase activity of cytosol from burn patients. Thus, decreased respiratory burst activity found in PMNs from individuals with thermal injury was associated with a specific, quantitative deficiency of p47-phox.

Adult↗

PubMed1996

Sequential systemic platelet-activating factor and interleukin 8 primes neutrophils in patients with trauma at risk of multiple organ failure.

Plasma from 33 patients at risk of multiple organ failure (MOF) after major trauma was tested for a priming effect on neutrophils, and for the presence of platelet-activating factor (PAF) activity and interleukin (IL) 8. Plasma sampled at 3, 6, 12 and 24 h after injury significantly primed normal neutrophils to release mean(s.e.m.) 1.26(0.19), 1.33(0.26), 1.04(0.14) and 0.86(0.13) nmol superoxide per min per 1.3 x 10(6) neutrophils respectively (P < 0.05). Priming at 3 h after injury was inhibited by mean(s.e.m.) 63.8(7.0) per cent by the PAF antagonist, WEB 2170 (P < 0.01). Mean(s.e.m.) plasma IL-8 was raised at 6 and 12 h after injury to 785(183) and 836(175) pg/ml (P < 0.01). At 12 h after injury the plasma IL-8 level correlated directly with the number of units of red blood cells transfused (r = 0.64, P < 0.01), and was significantly higher in the group of six patients who developed MOF (P < 0.05). These data suggest that after trauma the mediators PAF and IL-8 appear sequentially in the circulation, are potential mechanisms of circulating neutrophil priming, and that IL-8 may also be an early biochemical marker predicting the onset of MOF.

Adolescent↗

PubMed1996

Interleukin-6 stimulates neutrophil production of platelet-activating factor.

Interleukin-6 (IL-6) is an integral mediator of the acute phase response to injury and infection; an exaggerated IL-6 response has been associated with adverse clinical events. The precise role of IL-6 is unclear, but it appears capable of modulating the functional repertoire of mature neutrophils (PMNs). Our previous work demonstrated that IL-6 -stimulated PMNs are primed by lower concentrations of platelet-activating factor (PAF) than nonstimulated PMNs. Recently, we have found that IL-6 suppresses PMN apoptosis via a PAF-like mechanism. We hypothesized that IL-6 stimulates PMNs to produce PAF. PMNs isolated from healthy human donors were incubated with IL-6 (0.1-100 ng/ml) at 37 degrees C. Lipid production was measured by use of thin-layer chromatography, and PAF quantitated with a scintillation proximity assay. IL-6 (1 and 10 ng/ml) stimulated PMNs to produce increase quantities of PAF. PAF production was associated with an increase in PMN cytosolic calcium. These data may provide mechanistic insight into IL-6 regulation of PMN-mediated cytotoxicity and the role of PAF in mediating IL-6 effects on PMNs.

Amino Acid Sequence↗

PubMed1996

Interleukin-6 in the injured patient. Marker of injury or mediator of inflammation?

OBJECTIVE: The effects of interleukin (IL)-6 in the injured patient are examined in an attempt to clarify the potential pathophysiologic role of IL-6 in the response to injury. SUMMARY BACKGROUND DATA: Interleukin-6 is an integral cytokine mediator of the acute phase response to injury and infection. However, prolonged and excessive elevations of circulating IL-6 levels in patients after trauma, burns, and elective surgery have been associated with complications and mortality. The mechanistic role of IL-6 in mediating these effects is unclear. METHODS: A review of current literature is performed to summarize the origins, mechanisms of action, and biologic effects of IL-6 and to characterize the IL-6 response to injury. RESULTS: Interleukin-6 is a multifunctional cytokine expressed by a variety of cells after a multitude of stimuli, under complex regulatory control mechanisms. The IL-6 response to injury is uniquely consistent and related to the magnitude of the insult. Moreover, the early postinjury IL-6 response correlates with complications as well as mortality. CONCLUSIONS: Interleukin-6 appears to play an active role in the postinjury immune response, making it an attractive therapeutic target in attempts to control hyperinflammatory provoked organ injury.

Antigens, CD↗

PubMed1995

Recombinant human interleukin-1 receptor antagonist protects early myeloid progenitors in a murine model of cyclophosphamide-induced myelotoxicity.

Expression of hematoregulatory cytokines such as interleukin-1 (IL-1) in response to cytotoxic chemotherapy hastens hematopoietic recovery, but may also potentiate myelotoxicity if myeloid progenitors enter cell cycle before drug clearance. In the present study, the ability of recombinant human IL-1 receptor antagonist (IL-1ra) to protect hematopoietic progenitors was studied in a murine model of cyclophosphamide (CPA)-induced myelotoxicity. CF-1 female mice received 200 mg/kg CPA and either 10 mg/kg IL-1ra or an equal volume of 0.05% human serum albumin (HSA) intraperitoneally (i.p.), followed 12 hours later by IL-1ra or HSA. CPA and IL-1ra increased absolute neutrophil counts (ANCs) at days 2 (P = .001) and 14 (P = .0025) after CPA. In IL-1ra-treated mice, colony-forming units granulocyte-macrophage (CFU-GM)/tibia were increased twofold and threefold at days 2 (P = .0047) and 7 (P = .023), respectively, whereas high proliferative potential colony-forming cells (HPP-CFC)/tibia were decreased twofold to threefold at 8 hours (P = .039) and 24 hours (P = .0033), but were approximately threefold higher than HSA-treated mice at day 7 after CPA. Coadministration of CPA and IL-1 enhanced myelotoxicity compared with mice injected with CPA and IL-1ra or HSA. In vivo, IL-1ra protected HPP-CFC, but not CFU-GM, from hydroxyurea suicide after a single dose of CPA, suggesting that IL-1ra inhibited cycling of HPP-CFC. In vitro, IL-1ra did not alter proliferation of CFU-GM, but inhibited IL-1-enhanced proliferation of HPP-CFC. These data suggest that IL-1ra acts as an indirect negative regulator of hematopoiesis and protects HPP-CFC from CPA, possibly by inhibiting IL-1-enhanced proliferation of early myeloid progenitors.

Animals↗

PubMed1995

Postinjury neutrophil priming and activation: an early vulnerable window.

BACKGROUND: Generation of extracellular, cytotoxic superoxide anion (O2-) by polymorphonuclear neutrophils (PMNs) contributes to an unbridled inflammatory response that can precipitate multiple organ failure (MOF). Release of O2- is markedly enhanced when activated PMNs have been previously "primed" by inflammatory mediators, such as those expressed after trauma. We therefore hypothesized that PMN priming occurs as an integral part of the early inflammatory response to trauma. METHODS: PMNs were obtained from 17 high-risk patients with torso trauma at 3, 6, 12, 24, 48, and 72 hours after injury, as well as from 10 healthy donors, and the in vitro release of O2- was quantitated with a kinetic, superoxide dismutase (SOD)-inhibitable cytochrome c reduction assay. PMN O2- release was measured in the presence and absence of 1 mumol/L N-formyl-methionyl-leucyl-phenylalanine (fMLP) and after priming and activation with 20 nmol/L platelet-activating factor (PAF) and 1 mumol/L fMLP, respectively. RESULTS: In vitro PMN O2- release was used to determine whether postinjury PMNs were (1) activated in vivo, (2) primed in vivo, or (3) primable in vitro. Unstimulated PMNs from trauma patients spontaneously expressed modest amounts of O2- in vitro from 6 to 48 hours after injury, suggesting endogenous activation. Also, fMLP-activated PMNs collected between 3 and 24 hours after injury expressed more O2- than controls (p < or = 0.02), indicating in vivo, trauma-related priming. Furthermore, postinjury PMNs were maximally primed in vivo (i.e., in vitro exposure to PAF before fMLP activation failed to significantly enhance O2- release) as compared to PMNs treated with fMLP. CONCLUSIONS: These data indicate that major torso trauma (first hit) primes and activates PMNs within 3 to 6 hours after injury. Consequently, we postulate that postinjury priming of PMNs may create an early vulnerable window during which a second hit (e.g., a secondary operation or delayed hemorrhage) activates exuberant PMN O2- release, rendering the injured patient at high risk for MOF.

Adolescent↗

PubMed1995

Early neutrophil sequestration after injury: a pathogenic mechanism for multiple organ failure.

Polymorphonuclear neutrophils (PMNs) play a pivotal role in the inflammation that precedes multiple organ failure (MOF). In a rat model of MOF, PMNs become primed for enhanced superoxide anion (O2-) release and CD11b expression, sequester in end organs, and produce organ failure. Therefore, we hypothesized that circulating PMNs harvested in the first 24 hours after injury from trauma patients at risk for MOF would (1) exhibit a primed O2- release, (2) upregulate CD11b expression, and (3) show evidence of sequestration in tissues. Extracellular PMN O2- release and CD11b receptor expression were measured at 3, 6, 12, and 24 hours after injury in 33 torso trauma patients with Injury Severity Scores > 15; eight patients (24%) developed MOF. Healthy adults served as controls. PMNs after injury were primed for enhanced in vitro O2- release at 3, 6, 12, and 24 hours after injury, indicating prior in vivo priming. CD11b expression was also increased at 6, 12, and 24 hours after injury. Circulating PMN numbers increased sharply at 3 hours after injury, before decreasing dramatically at 6 and 12 hours, suggesting end organ sequestration. At 12 hours after injury, declines in circulating PMNs were significantly greater in MOF than in non-MOF patients (p < 0.05). These data indicate that PMNs are quickly mobilized into the circulation after injury and then primed for enhanced O2- release and CD11b expression. PMN priming appears to be a necessary preamble to PMN sequestration in patients with major torso trauma. Upregulation of PMN function, accompanied by subsequent end organ sequestration, may represent an important early event in the pathogenesis of MOF after injury.

Adult↗

PubMed1995

Postinjury neutrophil priming and activation states: therapeutic challenges.

Both hyperactivity and hypoactivity of neutrophils (PMNs) have been implicated in the pathogenesis of postinjury multiple organ failure. In this paper, the cellular and molecular mechanisms involved in the regulation of PMN O2- production are reviewed. In addition, relevant research laboratory techniques for measuring both intracellular and extracellular O2- release are outlined. In a pilot study PMN O2- release in response to a battery of PMN agonists was determined, and four functional states of the NADPH were defined: resting, primed, activated, and unresponsive. PMNs from normal adult volunteers are in the resting state. In contrast, PMNs from patients with severe torso trauma are primed and activated in the first 24 h postinjury, but, after 48 h, become unresponsive to both receptor-dependent (platelet activating factor and N-formyl-methyl-leucyl-phenylalanine) and receptor-independent (phorbol 12-myristate 13-acetate) activation. The ability to identify at-risk patients and provide a rationale for ameliorating PMN-mediated tissue injury in patients with hyperinflammation syndromes are discussed. In addition, the importance of identifying patients with PMNs that are unresponsive, and the necessity for increasing PMN function in these patients in order to reduce the risk of sepsis, are also discussed.

Humans↗

PubMed1994

Gene expression of hematoregulatory cytokines is elevated endogenously after sublethal gamma irradiation and is differentially enhanced by therapeutic administration of biologic response modifiers.

Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicorynomycolate (S-TDCM) presumably accelerates hematopoietic recovery after irradiation by enhancing expression of cytokines. However, the kinetics of the cytokine gene response to BRMs and/or irradiation are poorly defined. One hour after sublethal (7.0 Gy) 60Cobalt gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrated marked splenic gene expression for IL-1 beta, IL-3, IL-6, and granulocyte-CSF (G-CSF). Enhanced gene expression for TNF-alpha, macrophage-CSF (M-CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater gene expression for IL-1 beta, IL-3, TNF-alpha, and G-CSF at day 1 than any other BRM. When challenged with 2 LD50/30 of Klebsiella pneumoniae 4 days after irradiation, 100% of Sm-BRM-treated mice and 70% of S-TDCM-treated mice survived, whereas < or = 30% of mice treated with LPS, MPL, or TS survived. Thus, sublethal irradiation induces transient, splenic cytokine gene expression that can be differentially amplified and prolonged by BRMs. BRMs that sustained and/or enhanced irradiation-induced expression of specific cytokine genes improved survival after experimental infection.

Animals↗

PubMed1994

Endotoxin pretreatment inhibits neutrophil proliferation and function.

Gut ischemia/reperfusion (I/R) induces lung injury by a mechanism that involves neutrophils (PMNs). We have previously shown that endotoxin (LPS), when administered after gut I/R, amplifies this lung injury, while treatment with LPS prior to gut I/R prevents lung injury. The purpose of this study was to determine whether LPS pretreatment (Pre Rx) alters the PMN inflammatory component of the gut I/R injury. Specifically, we focused on whether LPS Pre Rx effected (i) PMN stem cell proliferation, (ii) gut I/R-induced PMN priming, and (iii) gut I/R-induced PMN lung sequestration. Bone marrow was harvested from normal and LPS-pretreated (0.5 mg/kg, ip, 3 days prior) rats, and colony forming units--granulocyte/macrophage (CFU-GM) were quantitated using a soft agar culture technique. In another experiment, normal and LPS-pretreated rats were subjected to gut I/R (45 min superior mesenteric artery occlusion/6 hr reperfusion), and blood and lungs were then harvested. The in vivo priming of PMN was assessed by measuring the difference in superoxide production (O2-) with and without the activating stimulus, N-formylmethionyl-leveyl-phenylalanine (fMLP). The quantity of myeloperoxidase (MPO) was used as an index of the number of PMN sequestered in lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Gut ischemia induces bone marrow failure and increases risk of infection.

Hemorrhagic shock leads to bone marrow (BM) failure and renders the host susceptible to infection. We hypothesized that splanchnic hypoperfusion may play a mechanistic role in this process. BM was harvested from normal rats and, on Postprocedure Days 1 and 3, from rats that had undergone laparotomy (LAP) or gut ischemia/reperfusion (I/R; 45 min superior mesentery artery occlusion). Granulocyte-macrophage colony-forming unit (CFU-GM) proliferation, a measure of BM myeloid progenitors, was quantitated using a standard soft agar culture technique. On Postprocedure Days 1 and 3, BM proliferation of CFU-GM was depressed in gut I/R rats, compared to control and LAP animals (P < 0.05). Next, six rats were subjected to I/R, LAP, ANEST (anesthesia control), or no treatment (NL, normal control); 1 day later, 3.5 x 10(7) Staphylococcus aureus, suspended in 0.25 ml of saline, were injected subcutaneously in four sites on the back of each animal. Five days later, the NL rats had developed 23 abscesses, ANEST 23, and LAP 22, while the gut I/R rats had 24. The abscesses were excised, weighed, and measured. The weight and size of abscesses were greater in the gut I/R animals (P < 0.05). In summary, gut I/R depressed BM proliferation and rendered animals susceptible to infection in a manner similar to that observed following hemorrhagic shock. These data suggest that splanchnic hypoperfusion, a common sequela of hemorrhagic shock, may play a mechanistic role in BM failure and infection after hemorrhage.

Abscess↗

PubMed1993

Iron chelation by deferoxamine in sickle cell patients with severe transfusion-induced hemosiderosis: a randomized, double-blind study of the dose-response relationship.

Transfusion-induced hemosiderosis is a serious and potentially life-threatening complication for some patients with sickle cell anemia. The use of high-dose intravenous deferoxamine (DFO) has become widespread in spite of a paucity of published data on safety and efficacy. We report a randomized double-blind study of the dose-response relationship of intravenous DFO in six subjects with sickle cell anemia and severe transfusion-induced hemosiderosis (serum ferritin 4100 to 14,176 ng/ml). Each subject received three different doses of intravenous DFO for 3 days each while consuming a constant diet. Total iron excretion (urine and fecal) was 91% greater at 180 mg/kg/day DFO than at 60 mg/kg/day DFO, and fecal iron excretion became a relatively larger proportion of total excretion at higher doses. Subsequent treatment for 3 months with 150 mg/kg/day DFO caused a 33% to 60% reduction in serum ferritin and demonstrable improvement in hepatic function in all patients. No toxicity was encountered, but DFO at 180 mg/kg/day was associated with a significant increase in fecal zinc excretion when compared with that observed at lower doses.

Adolescent↗

PubMed1992

Differential myelopoietic responsiveness of BALB/c (Itys) and C.D2 (Ityr) mice to lipopolysaccharide administration and Salmonella typhimurium infection.

Inheritance of the Ityr or the Itys allele of the Ity murine gene confers resistance or increased susceptibility, respectively, to Salmonella typhimurium infection. Recent studies have documented that Ity gene expression may determine net intracellular replication of S. typhimurium by modulating macrophage function. The purpose of this study was to determine if Ity gene expression modulated macrophage stem cell proliferation as well. To detect possible Ity-associated alterations in macrophage stem cell proliferation during endotoxin challenge or S. typhimurium infection, the congenic strain pair BALB/c (Itys) and C.D2-Idh-1, Pep-3 N20F8 (Ityr) were injected intraperitoneally with 25 micrograms of bacterial lipopolysaccharide (LPS) or approximately 10(3) S. typhimurium, and myelopoiesis was evaluated. At 72 h after LPS injection, both BALB/c and C.D2 mice developed comparable degrees of bone marrow hypocellularity and splenomegaly, and cell sizing profiles indicated a normal response to a single injection of LPS in both strains of mice. Although an inhibitor to colony-stimulating factor activity was detected in the sera and plasma of C.D2 mice, the number of myeloid stem cells cultured from the bone marrow and spleen of each mouse strain were comparable. S. typhimurium infection resulted in earlier symptoms, a larger bacterial load, a higher mortality rate, and a greater bone marrow hypocellularity and splenomegaly in BALB/c mice compared with those in C.D2 mice. Despite a dramatic increase in bacterial load, a decrease in both bone marrow and splenic myeloid stem cell numbers was noted in BALB/c mice, while stem cell numbers remained constant in C.D2 mice between days 3 and 5 and increased dramatically at day 7 after infection. These data suggest that BALB/c and C.D2 mice may exhibit a divergent myelopoietic response to S. typhimurium infection. It appears that a paradoxical failure of myelopoiesis in Itys mice during S. typhimurium infection may contribute to the observed increase in mortality.

Animals↗

PubMed1992

The myelopoietic effects of a Serratia marcescens-derived biologic response modifier in a mouse model of thermal injury.

The proliferative defects observed in phagocytic stem cells after major thermal injuries may be caused by an inadequate production of colony-stimulating factors (CSFs), a family of hemopoietic cytokines necessary for the production and function of granulocytes and monocytes. In this study a biologic response modifier (S-BRM) consisting of sized vesicles derived from the cell membrane and ribosomes of Serratia marcescens was investigated in a mouse model of thermal injury to determine its ability to augment postburn myelopoiesis. Treatment of burned mice with S-BRM was well tolerated and was associated with statistically significant increases in absolute numbers of circulating granulocytes and monocytes compared with burned mice receiving saline solution. In addition, the size of the splenic myeloid stem cell compartment, as measured by granulocyte-macrophage stem cell colony formation in soft agar, was markedly expanded. Finally, plasma levels of CSF were increased significantly in burned mice receiving S-BRM but were not elevated in burned littermates treated with saline solution. These data suggest that production of CSF is suboptimal after thermal injury and S-BRM is capable of up-regulating postburn myelopoiesis by causing the release of CSF into the systemic circulation.

Animals↗

PubMed1991

Gut bacterial translocation via the portal vein: a clinical perspective with major torso trauma.

Animal studies implicate gut bacterial translocation via the portal vein as a major factor in the pathogenesis of postinjury multiple organ failure (MOF). We therefore inserted portal vein catheters for sequential blood sampling in the operating room, at 6, 12, 24, and 48 hours, and 5 days postoperatively in 20 injured patients (13 blunt, seven penetrating; mean age, 34 years) requiring emergent laparotomy and who were at known risk for MOF. The mean Revised Trauma Score was 6.4 +/- 0.4, and the Injury Severity Score, 29.3 +/- 2.3. Twelve (60%) patients arrived in shock (SBP less than 90 torr). Eight (2%) of 212 portal blood cultures were positive; seven were presumed contaminants. The only positive systemic culture (total, 212) was a Staphylococcus aureus on day 5 in a patient with a concurrent staphyloccal pneumonia. In the first 48 hours, we could not detect endotoxin in portal or systemic blood. Additionally, simultaneous portal and systemic blood levels of complement fragment C3a, tumor necrosis factor, and interleukin-6 were nearly identical and, specifically, were not different in those patients who developed MOF. In summary, this prospective clinical study has not confirmed portal or systemic bacteremia within the first 5 days postinjury, despite an eventual 30% incidence of MOF.

Abdominal Injuries↗

PubMed1990

Inadequate granulopoiesis after major torso trauma: a hematopoietic regulatory paradox.

Late postinjury sepsis is largely the result of defective host defense including failure to maintain an adequate number of functioning phagocytic cells. In this study we used stem cell culture techniques to measure colony-stimulating activity and have quantitated the number of circulating myeloid stem cells to see if defects in granulopoiesis occur after major torso trauma. Forty-two acutely injured patients (13 blunt and 29 penetrating injuries; mean age, 29.7 years) undergoing laparotomy with an abdominal trauma index of 15 to 40 were studied prospectively. Blood samples were obtained on days 1, 5, and 10. Patients were segregated by injury severity: abdominal trauma index less than 25 (n = 25) versus abdominal trauma index greater than or equal to 25 (n = 17). The more severely injured (abdominal trauma index greater than or equal to 25) patients had fewer circulating granulocytes and monocytes. Colony-stimulating activity was below normal control levels in all patients and was decreased further with increased injury severity. The more severely injured patients had a blunted bone marrow response (significantly fewer circulating myeloid stem cells) and suffered more major septic complications (24% vs 8%). In conclusion, major trauma to the torso causes a paradoxic depression in granulopoiesis that worsens with increased injury severity and may contribute to late septic morbidity. This colony-stimulating activity deficiency state is similar to that seen after major burns and may be amenable to future modulation.

Abdominal Injuries↗

PubMed1989

TEN versus TPN following major abdominal trauma--reduced septic morbidity.

Recent animal models suggest that enteral feeding (TEN) compared to parenteral nutrition (TPN) improves resistance to infection. This prospective clinical trial examined the impact of early TEN vs. TPN in the critically injured. Seventy-five patients with an abdominal trauma index (ATI) greater than 15 and less than 40 were randomized at initial laparotomy to receive either TEN (Vivonex TEN) or TPN (Freamine HBC 6.9% and Trophamine 6%); both regimens contained 2.5% fat, 33% branched chain amino acids, and had a calorie to nitrogen ratio of 150:1. TEN was delivered via a needle catheter jejunostomy. Nutritional support was initiated within 12 hours postoperatively in both groups, and infused at a rate sufficient to render the patients in positive nitrogen balance. The study groups (TEN = 29 vs TPN = 30) were comparable in age, injury severity and initial metabolic stress. Jejunal feeding was tolerated unconditionally in 25 (86%) of the TEN group. Nitrogen balance remained equivalent throughout the study period, at day 5 TEN = -0.3 +/- 1.0 vs. TPN 0.1 +/- 0.8 gm/day. Traditional nutritional protein markers (albumin, transferrin, and retinol binding protein) were restored better in the TEN group. Infections developed in 5 (17%) of the TEN patients compared to 11 (37%) of the TPN group. The incidence of major septic morbidity was 3% (1 = abdominal abscess) in the TEN group contrasted to 20% (2 = abdominal abscess, 6 = pneumonia) with TPN. This clinical study demonstrates that TEN is well tolerated in the severely injured, and that early feeding via the gut reduces septic complications in the stressed patient.

Abdominal Injuries↗