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Biomedical subjects

Richard L Gamelli

Publications and source records attributed to Richard L Gamelli.

At least 37 records · Page 2Linked to original sources
PubMed2005

Old fashion clinical judgment in the era of protocols: is mandatory chest X-ray necessary in injured patients?

BACKGROUND: The ATLS Course advocates that injured patients have a chest x-ray (CXR) to identify potential injuries. The purpose of this study was to correlate clinical indications and clinician judgment with CXR results to ascertain if a selective policy would be beneficial. METHODS: Patients treated at a Level I trauma center over 12 months were prospectively evaluated. Before obtaining a CXR, signs, symptoms, and history suggestive of thoracic injury were identified. Additionally, a trauma surgeon (TS) recorded whether in their judgment a CXR was clinically indicated. These findings were compared with final CXR diagnoses. The sensitivity of individual clinical indicators, combinations of clinical indicators, and TS judgment for CXR abnormalities were calculated with a 95% confidence interval. RESULTS: During the twelve-month study period, data were acquired on 772 patients (age 0-102 years). Seventy percent were male and 86.0% were injured by blunt force. Only 29% (N = 222) of the patients manifested one or more of the clinical indicators (signs and symptoms). The negative predictive value for the TS judgment was 98.2% which was superior to the clinical indicators. Reliance on the opinion of the TS to determine the need for a CXR would have eliminated 49.9% of CXRs and avoided hospital and radiologist reading charges totaling $100,078.22. CONCLUSION: Mandatory CXR for all trauma patients has a low yield for abnormal findings. A selective policy relying on surgical judgment guided by clinical indicators is safe and efficacious while reducing cost and conserving resources.

Accidental Falls↗
PubMed2005

Reasons to omit digital rectal exam in trauma patients: no fingers, no rectum, no useful additional information.

BACKGROUND: Performance of digital rectal examination (DRE) on all trauma patients during the secondary survey has been advocated by the Advanced Trauma Life Support course. However, there is no clear evidence of its efficacy as a diagnostic test for traumatic injury. The purpose of this study is to analyze the value of a policy mandating DRE on all trauma patients as part of the initial evaluation process and to discern whether it can routinely be omitted. METHODS: Prospective study of patients treated at a Level I trauma center. Clinical indicators other than DRE (OCI) denoting gastrointestinal bleeding (GIB), urethral disruption (UD), or spinal cord injury (SCI) were sought and correlated with DRE findings suggesting the same. Impression of the examining physician as to the need and value of DRE was also studied. Patients with a Glasgow Coma Scale Score (GCS) of 3 and pharmacologically paralyzed were excluded from the SCI analyses. UD analysis included only males. RESULTS: In all, 512 cases were studied (72% male, 28% female) ranging in age from 2 months to 102 years. Thirty index injuries were identified in 29 patients (6%), 17 SCI (3%), 11 GIB (2%), and 2 UD (0.4%). DRE findings agreed positively or negatively with one or more OCI of index injuries in 93% of all cases (92% seeking SCI, 90% seeking GIB, 96% seeking UD). Overall, negative predictive value of DRE was the same as that of OCI, 99% (SCI 98% versus 99%, GIB, 97% versus 99%, UD both 100%). Positive predictive value for DRE was 27% and for OCI 24% (SCI 47% versus 44%, GIB 15% versus 18%, UD 33% versus 6%). Efficiency of DRE was 94% and OCI was 93%. For confirmed index injuries, indicative DRE findings were associated with 41% and OCI 73% (SCI 36% versus 79%, GIB 36% versus 73%, UD 50% versus 100%). OCIs were present in 81% of index injury cases. In all index injury cases where OCIs were absent, positive DRE findings were also absent. DRE was felt to give additional information in 5% of all cases and change management in 4%. In cases where the clinician felt DRE was definitely indicated (29%) it reportedly gave no additional information in 85% and changed management in 11%. CONCLUSION: DRE is equivalent to OCI for confirming or excluding the presence of index injuries. When index injuries are demonstrated, OCI is more likely to be associated with their presence. DRE rarely provides additional accurate or useful information that changes management. Omission of DRE in virtually all trauma patients appears permissible, safe, and advantageous. Elimination of routine DRE from the secondary survey will presumably conserve time and resources, minimize unpleasant encounters, and protect patients and staff from the potential for further harm without any significant negative impact on care and outcome.

Adolescent↗
PubMed2004

Impaired intestinal immunity and barrier function: a cause for enhanced bacterial translocation in alcohol intoxication and burn injury.

Alcohol intoxication is being recognized increasingly as the major factor in pathogenesis after burn injury. Findings from multiple studies support the suggestion that, in comparison with burn-injured patients who sustained injury in the absence of alcohol intoxication, burn-injured patients who sustained injury under the influence of alcohol exhibit higher rates of infection and are more likely to die. Thus, infection becomes the primary cause of death in burn-injured patients. Because the intestine is considered to be a major source of bacteria, studies in experimental animals have been designed to examine whether alcohol intoxication before burn injury enhances bacterial translocation from the intestine. Results of these studies have shown a several-fold increase in bacterial translocation from the intestine in the group of animals receiving combined insult of alcohol intoxication and burn injury compared with findings for the groups receiving either insult alone. Alcohol intoxication and burn injury independent of each other have also been shown to cause an increase in bacterial translocation. The gastrointestinal tract normally maintains a physical mucosal and immunologic barrier that provides an effective defense in keeping bacteria within the intestinal lumen. However, in injury conditions these defense mechanisms are impaired. Intestinal bacteria consequently gain access to extraintestinal sites. Intestine-derived bacteria are implicated in causing systemic infection and in subsequent multiple organ dysfunction in both immunocompromised patients and patients with injury, such as burn and trauma. In this article, we discuss three potential mechanisms that are likely to contribute to the increase in bacterial translocation in alcohol intoxication and burn injury: (1) increase in bacterial growth in the intestine, (2) physical disruption of mucosal barrier of the intestine, and (3) suppression of the immune defense in the intestine.

Alcoholic Intoxication↗
PubMed2004

Medical student electives in general surgical subspecialties.

BACKGROUND: The purpose of the study was to evaluate how well the burn, trauma, and peripheral vascular third-year medical school electives meet the objectives of the six ACGME core competencies. METHODS: Medical school graduates from 1999 to 2002 completed a survey that consisted of 13 demographic/miscellaneous questions, and 28 core competency questions. RESULTS: In all, 168 of 500 students responded for a 34% response rate. All three general surgical electives ranked above average in meeting objectives in the areas of: basic science, performing complete histories and physicals, writing logical and legible notes, creating complete assessments and plan, making decisions with evidence based medicine, performing basic procedures, interpreting test results, and maintaining professional attitudes. The burn elective ranked significantly higher in 16 of 28 objectives (P < 0.05) and the trauma elective ranked significantly higher in two of 28 objectives (P < 0.05). CONCLUSIONS: Despite a narrower professional focus, three general surgical subspecialty electives meet objectives in five of the six competencies set forth by the ACGME (and adopted by our medical school as objectives for the ideal graduate). The highly organized and structured burn elective can be used as a template for improving all surgical rotations to meet the six core competencies for third-year students.

Adult↗
PubMed2004

Protection against concanavalin A-induced hepatocyte apoptosis by molsidomine is time-dependent.

BACKGROUND: Viral hepatitis and autoimmune liver diseases cause hepatocyte apoptosis. Concanavalin A (Con A)-induced hepatitis resembles human viral hepatitis and autoimmune hepatitis. The role of nitric oxide (NO) in liver injury was controversial in different liver injury models. We hypothesize both endogenous and exogenous NO protect liver against Con A-induced liver injury. Molsidomine is metabolized into SIN-1 by the liver, and SIN-1 subsequently generates NO. So, molsidomine was used as a NO donor in this study. STUDY DESIGN: To study a protective role of endogenous NO in Con A-induced liver injury, mice were pretreated with a specific inducible nitric oxide synthase (iNOS) inhibitor, L-N(6)-(1-iminoethyl)-lysine (L-NIL), before Con A challenge. To study a time-dependent protection against Con A-induced liver injury, animals were either given molsidomine, a NO donor, before or after Con A administration. Serum alanine aminotranferase (ALT) was analyzed. Liver samples were subjected to DNA fragmentation assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling stain, Western blot analysis, and caspase activity assays. RESULTS: Animals pretreated with L-NIL had significantly increased serum ALT levels compared with those challenged with Con A alone; but pretreatment with molsidomine dramatically decreased ALT levels in L-NIL-pretreated animals or in animals that received Con A alone. Administration of molsidomine 30 minutes before or 1, 2, and 3 hours after Con A injection significantly reduced serum ALT levels and attenuated hepatocyte apoptosis from caspase inactivation. The ALT reduction was associated with inhibition of both caspase-3 and caspase-8 activation and reduction of hepatocyte apoptosis. CONCLUSIONS: Endogenous NO plays an important protective role against Con A-induced liver injury by reducing hepatocyte apoptosis. Administration of a NO donor early after Con A injection protects the liver from injury. This is the first study demonstrating a time-dependent inhibition of liver injury induced by Con A administration.

Alanine Transaminase↗
PubMed2004

Combined alcohol and burn injury differentially regulate P-38 and ERK activation in mesenteric lymph node T cell.

Recent studies from our laboratory have suggested that acute alcohol ingestion prior to burn injury enhances gut bacterial translocation by suppressing T cell-mediated intestinal immune defense. To determine the mechanism responsible for suppressed T cell function, we examined the activation of mitogen-activated protein kinases (MAPK) members p-38 and ERK-1/2. Both p-38 and ERK-1/2 are known to play a significant role in the T cell proliferation and their cytokine production. Rats were gavaged with ethanol to achieve a blood alcohol level of approximately 100 mg/dl, before they were subjected to a 25% total body surface area burn injury. Two days after injury, rats were sacrificed and mesenteric lymph node (MLN) T cells were isolated and their ability to proliferate in response to anti-CD3 was determined. For p-38 and ERK-1/2 determination, T cells were divided into two groups. Cells in one group were stimulated with anti-CD3 for 3 min and lysed. The cells in the second group were cultured for approximately 18 h in the presence of anti-CD3 and lysed. MAPK status in 18-h cultured cells allowed us to determine whether or not the changes in p-38 and ERK-1/2 are transient or persist in the proliferating cells. Two days after injury, anti-CD3-mediated MLN T cell proliferation was more suppressed in rats gavaged with alcohol prior to burn injury compared to rats receiving either burn injury alone or sham-injured rats regardless of their exposure. Western blot analyses showed significant inhibition of ERK-1/2 phosphorylation in both freshly isolated and 18-h cultured T cells from alcohol and burn-injured rats compared to the sham rat T cells. The inhibition of p-38 phosphorylation in T cells derived from alcohol and burn-injured rats was found to be transient as no significant difference in p-38 phosphorylation was noted between the 18 h incubated MLN T cells of sham and alcohol and burn-injured rats. Taken together, our findings suggest that low levels of ERK-1/2 activation is likely to play a significant role in MLN T cell proliferative suppression in alcohol and burn-injured rats.

Animals↗
PubMed2004

Exacerbation of intestinal permeability in rats after a two-hit injury: burn and Enterococcus faecalis infection.

OBJECTIVE: To determine alterations in intestinal epithelial permeability to solutes in burn injured rats with and without Enterococcus faecalis infection and the role of neutrophils in the intestinal permeability changes. DESIGN: Prospective sham-controlled animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats were subjected to 30% total body surface burn (B group), E. faecalis infection (EF group) induced via intra-abdominal implantation of bacterial pellet, or combination of burn injury and E. faecalis infection (B+EF group). MEASUREMENTS AND MAIN RESULTS: In vivo measurements of intestinal permeability were carried out after intraluminal injection of H lactulose and C mannitol in the ileum of sham, B, EF, and B+EF groups of rats, 1 and 2 days after injury. Lactulose permeability was increased in the injured rat groups (B, EF, B+EF) on day 1 postinjury compared with sham. The combined injury group (B+EF) had the highest level of lactulose permeability. Although a significant change in lactulose permeability from day 1 to day 2 postinjury could not be demonstrated in the B and EF groups, lactulose permeability in the B+EF group on day 2 postinjury markedly decreased from day 1 but was still significantly higher than that in the sham group. Mannitol permeability was increased in all injured rat groups on day 1 postinjury; on day 2 it remained elevated post-B, decreased post-EF, and further increased after B+EF. Ex vivo measurements of lactulose movements across intestinal epithelial monolayers (IEC-18) were carried out in the presence of blood neutrophils from sham, B, EF, or B+EF rats. We also measured ex vivo transepithelial migration of neutrophils from sham, B, EF, or B+EF rat groups. Neither the transepithelial lactulose movement in the presence of neutrophils from, nor neutrophil migration in, the B or EF rats was significantly different from sham. However, a significant increase in transepithelial lactulose movement and neutrophil migration occurred in the B+EF group. Immunoblot analyses and in situ histochemical localizations of intestinal tight junction proteins, occludin and claudin-3, showed decreases in the distribution of occludin but not claudin-3 in the B, EF, and B+EF groups. CONCLUSIONS: Alterations in intestinal solute permeability and disruption of tight junction integrity after a two-hit injury with burn and E. faecalis infection, but not after individual injuries of burn or E. faecalis infection, are likely associated with heightened neutrophil flux across the intestinal epithelium.

Animals↗
PubMed2004

Bone marrow norepinephrine mediates development of functionally different macrophages after thermal injury and sepsis.

OBJECTIVE: We sought to determine the influence of thermal (burn) injury with sepsis and norepinephrine on the clonogenic potential and functional cytokine response to lipopolysaccharide (LPS) stimulation in nonmyeloid committed (CD117) and myeloid committed (ER-MP12) bone marrow progenitor cells. SUMMARY AND BACKGROUND DATA: We have previously demonstrated that norepinephrine stimulated myelopoiesis after burn injury and sepsis, but the site of this stimulation in monocyte development is unknown. In the present study the influence of norepinephrine on the developmental hierarchy of bone marrow cells after thermal injury and sepsis was determined by assessing the clonogenic potential and LPS-stimulated cytokine responses of mature macrophages derived from CD117 and ER-MP12 bone marrow progenitor cells. METHODS: Tissue and bone marrow norepinephrine content was ablated by chemical sympathectomy with 6-hydroxydopamine treatment. CD117 and ER-MP12 bone marrow cells were isolated using antibody-linked magnetic microbeads. Clonogenic potential in response to colony-stimulating factors was determined. Both progenitor cell types were differentiated to mature macrophages in vitro and tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 cytokine responses to LPS provocation were determined. RESULTS: The macrophage- and granulocyte-macrophage colony-stimulating factor responsive clonogenic potential was increased with burn sepsis, suggesting an expansion of both progenitor populations. Such increases were greatly reduced with prior depletion of norepinephrine. TNF-alpha and IL-6 cytokine responses to LPS were markedly influenced by the specific progenitor cells involved as well as the injury conditions and the status of norepinephrine prior to injury. In burn sepsis the depletion of norepinephrine resulted in a dramatic decrease in both IL-6 and TNF-alpha production by both progenitor-derived macrophages. CONCLUSIONS: Depletion of norepinephrine attenuated burn and burn sepsis-induced bone marrow progenitor clonal growth in response to macrophage- and granulocyte-macrophage colony-stimulating factor. Functional phenotypes of bone marrow progenitor-derived macrophages are greatly influenced by norepinephrine and the milieu created by thermal injury and sepsis.

Animals↗
PubMed2004

Burn injury and pulmonary sepsis: development of a clinically relevant model.

BACKGROUND: Despite improvements in the early resuscitation of the critically injured, mortality from multiple organ failure has remained stable, with the lung often the first organ to fail. Early intubation and mechanical ventilation predispose patients to the development of pneumonia and respiratory failure. Our objective was to establish a murine model of combined injury, consisting of burn/trauma and pulmonary sepsis with reproducible end-organ responses and mortality. METHODS: Male B6D2F1 mice were divided into four groups: burn/infection (BI), burn (B), infection (I), and sham (S). Burned animals had a full-thickness 15% dorsal scald burn. BI and I groups were inoculated intratracheally with Pseudomonas aeruginosa (3-5 x 103 colony-forming units). S and B animals received saline intratracheally. All animals were resuscitated with 2 mL of intraperitoneal saline. Mortality was recorded at 24, 48, and 72 hours. Bacterial sepsis was confirmed by tissue Gram's stain of the lungs and positive organ and blood cultures for Pseudomonas aeruginosa. Femoral bone marrow cells were collected at 72 hours from surviving animals. Clonogenic potential was assessed by response to macrophage (M) colony-stimulating factor (CSF) and granulocyte-macrophage (GM) CSF in a soft agar assay and the data were represented as colonies per femur. Isolated alveolar macrophages and whole lung tissue were assayed for levels of the inflammatory cytokines tumor necrosis factor-alpha and interleukin-6. RESULTS: Mortality at 72 hours was 30% in BI, 12% in I, and <10% in B and S groups. Pneumonia was documented in all infected animals at 24 hours by Gram's stain and positive tissue cultures for Pseudomonas aeruginosa. Systemic sepsis as confirmed by blood, and remote organ cultures was seen in BI animals only. Significantly increased responsiveness to M-CSF stimulations was noted in all groups (BI, 8,291 +/- 1,402 colonies/femur; B, 6,357 +/- 806 colonies/femur; and I, 8,054 +/- 1,112 colonies/femur; p < 0.05) relative to sham (3,369 +/- 883 colonies/femur, p < 0.05). Maximal responsiveness to GM-CSF stimulation was noted in the BI group (11,932 +/- 982 colonies/femur, p < 0.05), and similar GM responsiveness was noted in all other groups (B, 7,135 +/- 548 colonies/femur; I, 7,023 +/- 810 colonies/femur; and S, 6,829 +/- 1,439 colonies/femur). Alveolar macrophage release of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 increased in all animals, but the magnitude of increase was not proportional to the strength of the inciting stimulus. CONCLUSION: Although minimal perturbations were seen after burn or pulmonary infection alone, the combined insult of burn and pulmonary sepsis resulted in statistically significant hematopoietic changes with increased monocytopoiesis. Only the combined injury resulted in systemic sepsis and significantly increased mortality. We have developed a clinically relevant model of trauma and pulmonary sepsis that will allow further clarification of the inflammatory response after injury and infection.

Animals↗
PubMed2004

Ten year experience of burn, trauma, and combined burn/trauma injuries comparing outcomes.

BACKGROUND: Percent total body surface area (TBSA) burn, inhalation injury (INH), and age all have been shown to be independent predictors of mortality in burn victims. Little is known regarding patients sustaining combined thermal and mechanical injuries in relation to either injury sustained in isolation or with regard to these variables. This descriptive study profiles the 10-year experience of a single American Burn Association/American College of Surgeons verified Level I trauma and burn center and the treatment of this patient population. METHODS: A retrospective review of all burn and trauma patients admitted between 1990 and 2000. Patients were divided into three groups; Burn only (B), Trauma only (T), and combined Burn/Trauma (B/T). Groups were compared with respect to age, TBSA burn, length of stay (LOS), Injury Severity Score (ISS), INH and mortality. These groups were then compared with B, T and B/T patients from the National Burn Repository (NBR) and National Trauma Data Bank (NTDB). Student's t test and chi tests were performed, as well as multiple logistic regression to identify independent predictors of mortality. p <0.05 was considered significant. RESULTS: Through our trauma registry, 24,093 patients were identified (T=22,284, B=1717 and B/T=92). When comparing B and T, there was no difference in age, LOS, ISS, or mortality to those patients in the NBR or NTDB. B/T patients showed significantly increased percentage with INH (B/T=44.5% versus 11%), increased LOS (B/T=18 days versus 13.7 B and 5.3 T) and increased mortality (B/T=28.3% versus 9.8% B and 4.3% T). B/T were also significantly older (B/T=40.1 years versus 31.0 B and 35.1 T). When these variables are compared with the NBR and the NTDB benchmarks, mortality (28.3% versus 11.6% NBR and 7.0% NTDB) and ISS (23 versus 11.7 NTDB) were significantly higher with no difference in age (40.1 versus 33.4 NTDB, 35.9 NBR), LOS (18 days versus 23.3 NBR) or TBSA (20.8% versus 19.5% NBR). Multiple logistic regression comparing TBSA, age, ISS and INH of survivors versus non-survivors identified only ISS as an independent predictor of mortality. CONCLUSION: B combined with T presents a rare injury pattern that has a synergistic effect on mortality. Physicians and caregivers should be aware of a 2-3 fold increase in the incidence of INH in this population, and increased mortality despite similar TBSA burned when compared with patients with B as the sole mechanism; ISS appears to be an independent predictor of mortality in this combined injury pattern.

Adolescent↗
PubMed2003

Advanced age negatively influences mesenteric lymph node T cell responses after burn injury.

While the pathophysiology of burn injury is well established in young adults, the factors that contribute to pathogenesis and increased death in elderly burn patients are not defined. The purpose of this study is to determine the effects of burn injury on mesenteric lymph node (MLN) T cell responses in young and aged mice. MLN is a cluster of lymph nodes that drains various parts of the intestine and is known to play role in clearance bacteria originating from the intestinal lumen. Results presented here suggest a significant suppression in Con A-induced MLN cell proliferation and IL-2 production in uninjured aged mice compared with uninjured young mice. Following 24 h after injury, although, a significant decrease in lymph node cell proliferation and IL-2 production was observed in both young and aged mice compared with their respective sham-injured animals, the suppression was more in aged mice. In addition we found a reduction in IFN-gamma, a Th-1 cytokine by MLN T cells from aged burned mice relative to young burn (P<0.05) or sham-injured mice (P<0.01). The Th-2 cytokine IL-4, on the other hand, was significantly increased in both young and aged burn-injured mice MLN T cells compared with their respective sham-injured mice. These results show that burn injury causes a greater suppression in MLN T cells ability to proliferate and a more pronounced shift to Th-2 phenotype in aged mice as compared with young mice. Such decreases in T cell functions may impair MLN's ability to clear the bacterial pathogens originating from intestine and thereby contribute to increased pathogenesis in injured host.

Age Factors↗
PubMed2003

Prostaglandin E2 mediates growth arrest in NFS-60 cells by down-regulating interleukin-6 receptor expression.

Interleukin-6 (IL-6), a potent myeloid mitogen, and the immunosuppressive prostanoid prostaglandin E2 (PGE2) are elevated following thermal injury and sepsis. We have previously demonstrated that bone marrow myeloid commitment shifts toward monocytopoiesis and away from granulocytopoiesis during thermal injury and sepsis and that PGE2 plays a central role in this alteration. Here we investigated whether PGE2 can modulate IL-6-stimulated growth in the promyelocytic cell line, NFS-60, by down-regulating IL-6 receptor (IL-6r) expression. Exposure of NFS-60 cells to PGE2 suppressed IL-6-stimulated proliferation as well as IL-6r expression. Receptor down-regulation is functionally significant since IL-6-induced signal transduction through activators of transcription (STAT)-3 is also decreased. Down-regulation of IL-6r correlated with the ability of PGE2 to arrest cells in the G0/G1 phase of the cell cycle. PGE2 appears to signal through EP2 receptors. Butaprost (EP2 agonist) but not sulprostone (EP3 agonist) inhibited IL-6-stimulated proliferation. In addition, an EP2 antagonist (AH6809) alleviated the anti-proliferative effects of PGE2. NFS-60 cells express predominantly EP2 and EP4 receptors. While PGE2 down-regulated both the IL-6r protein and mRNA expression, it had no influence on EP2 or EP4 mRNA expression. The present study demonstrates that PGE2 is a potent down-regulator of IL-6r expression and thus may provide a mechanistic explanation for the granulocytopenia seen in thermal injury and sepsis.

Animals↗
PubMed2003

Mechanism of injury does not predict acuity or level of service need: field triage criteria revisited.

BACKGROUND: Trauma systems use specific criteria based on physiologic, anatomic, and mechanistic factors for field triage. The purpose of this study was to evaluate the emergency department disposition of patients not meeting mandatory criteria (ie, physiologic or anatomic factors) for triage to a trauma center and the potential for over- or undertriage. METHODS: This was a retrospective review of trauma admissions from July 1999 to June 2001, to a level I trauma center. Triage criteria were classified as physiologic factors (n=300), anatomic factors (n=115), or mechanistic factors (n=414), according to the criteria of the American College of Surgeons Committee on Trauma. Physiologic and anatomic factors were combined and compared with mechanistic factors. RESULTS: There were 1253 admissions during the study period. Sixty-six percent (n=830) met study inclusion criteria. Fifty percent (n=413) were admitted to the intensive care unit or operating room. Approximately 50% of each group (physiologic/anatomic, 52%; mechanistic, 47%; P=.08) were admitted directly to the operating room or to the intensive care unit. CONCLUSIONS: Patients not meeting mandatory criteria for transfer to a trauma center often have serious injuries that require a higher level of care. The inclusion of all or select mechanistic criteria for evaluation at a trauma center is appropriate to achieve an acceptable rate of clinical undertriage, as well as resource undertriage and its subsequent complications.

Emergency Service, Hospital↗
PubMed2003

The nitric oxide donor molsidomine improves survival and reduces hepatocyte apoptosis in cholestasis and endotoxemia.

BACKGROUND: Cholestasis and endotoxemia have been demonstrated to cause hepatocyte apoptosis through caspase-mediated pathways. In vitro nitric oxide (NO) donors reduce hepatocyte apoptosis and caspase activation in several models. The nitric oxide donor molsidomine improves survival in an in vivo model of endotoxemia. We tested the effect of molsidomine on survival and hepatocyte apoptosis in a model of obstructive jaundice and endotoxemia. STUDY DESIGN: Sprague-Dawley rats underwent common bile duct ligation on day 1. On day 3, animals were given either 100 mg/kg of molsidomine or an equivalent volume of saline, and 30 minutes later they were given endotoxin 3 mg/kg or 10 mg/kg intravenously. Animals were sacrificed 4 or 16 hours after endotoxin injection. Serum samples were analyzed for alanine aminotransferase and frozen liver samples were analyzed for caspase 3 activity. Paraffin-embedded liver sections were assayed for apoptosis using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Survival was measured in a separate experiment in which animals underwent the same protocol, but were given three different doses of endotoxin and were observed for 72 hours before sacrifice. RESULTS: At endotoxin 3 mg/kg, the 72-hour survival in saline-treated animals was 92%, which decreased to 45% at 10 mg/kg and to 29% at 15 mg/kg. All of the molsidomine-treated animals survived all endotoxin doses. Alanine aminotransferase was reduced in molsidomine-treated animals compared with those treated with saline. Apoptosis was attenuated in molsidomine-treated animals. Caspase 3 activity was decreased in molsidomine-treated animals compared with those given saline. CONCLUSIONS: Molsidomine attenuates caspase activation and hepatocyte apoptosis and improves survival after cholestatic endotoxic injury.

Animals↗
PubMed2003

The effect of thrombocytopenia on dermal wound healing.

The immediate appearance of platelets in wounds and the ability of platelets to release growth factors suggest that platelets are an important trigger of the tissue repair process. To examine the effect of systemic thrombocytopenia on both the inflammatory and proliferative aspects of wound healing, adult mice were rendered thrombocytopenic by intraperitoneal administration of a rabbit antimouse platelet serum. Full-thickness excisional dermal wounds were prepared and analyzed for inflammatory cell content, growth factor production, reepithelialization, collagen synthesis, and angiogenesis at multiple time points after injury. Compared to control mice, thrombocytopenic mice exhibited significantly altered wound inflammation. Wounds of thrombocytopenic mice contained significantly more macrophages and T cells, yet exhibited neutrophil content similar to wounds from control mice. Surprisingly, thrombocytopenic mice exhibited no delay in the reparative aspects of wound healing. The rate of wound reepithelialization, collagen synthesis, and angiogenesis was nearly identical for thrombocytopenic and control mice. Analysis of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor beta1, keratinocyte growth factor, and epidermal growth factor revealed no difference in the levels of these growth factors in the wounds of control and thrombocytopenic mice. Taken together, the results suggest that the presence of platelets may influence wound inflammation, but that platelets do not significantly affect the proliferative aspects of repair, including wound closure, angiogenesis, and collagen synthesis.

Animals↗
PubMed2003

Effect of acute ethanol exposure on the dermal inflammatory response after burn injury.

BACKGROUND: More than 100,000 people each year are admitted to U.S. hospitals for severe burn injury. Strikingly, ethanol use prior to injury is apparent in nearly 50% of burn patients, rendering them six times more likely to die from infection than patients not exposed to ethanol. We previously reported that the kinetics and magnitude of neutrophil chemokine production and subsequent accumulation of neutrophils in the lung was dramatically altered when ethanol exposure preceded injury. Here, we tested whether burn injury and ethanol exposure combined, altered susceptibility to infection, neutrophil chemoattractant production, and neutrophil accumulation at the site of the burn wound. METHODS: Male B(6)D(2)F1 mice were administered a dose of ethanol designed to achieve 90-100 mg/dl circulating levels and 30 min later subjected to a 15% total body surface area dorsal scald injury. Susceptibility to topically applied Pseudomonas aeruginosa was examined. At various times after injury, burn wound and normal tissues were collected for assessments of neutrophil counts, myeloperoxidase quantitation, and neutrophil chemoattractant (KC and MIP-2) production. RESULTS: Ethanol exposure prior to burn injury enhanced susceptibility to infection after burn and was associated with significantly elevated production of KC, but not MIP-2, at the wound site. Despite the enhanced elevation of KC, neutrophil accumulation in the wounds of ethanol exposed, burn injured mice did not differ from those that received burn injury alone. TNFalpha (a potent activator of neutrophils), however, was found to be significantly elevated in the wounds of mice that received only burn injury, but not in those that received injury in combination with prior ethanol exposure. CONCLUSION: In the presence of ethanol, neutrophils are adequately recruited to the site of burn injury, but their host defense functions are impaired, perhaps due to the lack of proinflammatory cytokines such as TNFalpha.

Animals↗
PubMed2003

Enteral nutritional supplementation prevents mesenteric lymph node T-cell suppression in burn injury.

OBJECTIVE: To determine the effects of an immune-enhancing diet supplemented with glutamine, arginine, fish oil, and dietary nucleotides on mesenteric lymph node T-cell functional disturbances encountered after burn injury in rats. DESIGN: A prospective animal study. SETTING: University medical center research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats received a 30%, total body surface, full-thickness burn. Burn-injury rats received the IMPACT diet supplemented with glutamine, arginine, fish oil, and nucleotides or arginine, fish oil, and nucleotides, or an isocaloric/isonitrogenous diet without supplementation with glutamine, arginine, fish oil, or nucleotides. MEASUREMENTS AND MAIN RESULTS: Two days after injury, we found a significant decrease in the proliferation and interleukin-2 production by mesenteric lymph node T cells derived from rats fed on conventional chow compared with sham rats. The burn-related suppression of mesenteric lymph node T-cell proliferation and interleukin-2 production was prevented when the rats were fed on a high-protein diet rich in glutamine, arginine, fish oil, and nucleotides. We found that the immunostimulatory effects of the enriched diet are dependent on the presence of glutamine, arginine, fish oil, and nucleotides as feeding of rats on the isocaloric/isonitrogenous diet deficient in glutamine, arginine, fish oil, and nucleotides did not prevent the burn-related suppression of mesenteric lymph node T-cell dysfunction. Finally, our studies suggested that immunostimulatory effects of the diet are mediated by prostaglandin E(2) regulation of T-cell activation signaling molecule P59fyn. CONCLUSION: These results suggest that a diet rich in arginine, fish oil, and nucleotides, with and without glutamine, can effectively prevent T-cell dysfunction encountered after burn injury.

Analysis of Variance↗