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Bruce A Cairns

Publications and source records attributed to Bruce A Cairns.

At least 19 recordsLinked to original sources
PubMed2006

Lymphopenia-induced homeostatic proliferation of CD8+ T cells is a mechanism for effective allogeneic skin graft rejection following burn injury.

Burn patients are immunocompromised yet paradoxically are able to effectively reject allogeneic skin grafts. Failure to close a massive burn wound leads to sepsis and multiple system organ failure. Immune suppression early (3 days) after burn injury is associated with glucocorticoid-mediated T cell apoptosis and anti-inflammatory cytokine responses. Using a mouse model of burn injury, we show CD8+ T cell hyperresponsiveness late (14 days) after burn injury. This is associated with a CD8+ T cell pro- and anti-inflammatory cytokine secretion profile, peripheral lymphopenia, and accumulation of a rapidly cycling, hyperresponsive memory-like CD8+CD44+ IL-7R- T cells which do not require costimulation for effective Ag response. Adoptive transfer of allospecific CD8+ T cells purified 14 days postburn results in enhanced allogeneic skin graft rejection in unburned recipient mice. Chemical blockade of glucocorticoid-induced lymphocyte apoptosis early after burn injury abolishes both the late homeostatic accumulation of CD8+ memory-like T cells and the associated enhanced proinflammatory CD8+ T cell response, but not the late enhanced CD8+ anti-inflammatory response. These data suggest a mechanism for the dynamic CD8+ T cell response following injury involving an interaction between activation, apoptosis, and cellular regeneration with broad clinical implications for allogeneic skin grafting and sepsis.

Adoptive Transfer↗
PubMed2006

Low-avidity CD8lo T cells induced by incomplete antigen stimulation in vivo regulate naive higher avidity CD8hi T cell responses to the same antigen.

We have previously reported that multiple injections of soluble MHC class I tetramers assembled with wild-type HY peptide induces unresponsiveness to male skin grafts in naive female C57BL/6 (B6) mice. Induction of unresponsiveness is dependent on a population of unresponsive allospecific CD8(lo )T cells. Reduced expression of CD8 acts to limit a T cell response to HY peptide by limiting the avidity window of effective signal transduction. We and others have demonstrated that CD8(lo) T cells are an alternative stable phenotype of CD8alphabeta(+) T cells in vitro and in vivo after antigen stimulation. We show here that CD8(lo) T cells can suppress naive CD8(+) T cell responses to HY antigen in vitro and male skin graft rejection in vivo after adoptive transfer into female recipients. These novel regulatory T cells express surface TGF-beta1 and secrete T cytotoxic 2 cytokines after antigen-specific stimulation. Anti-TGF-beta antibody and latency-associated peptide inhibit the suppressive effects in vitro. We also show that HY-specific memory CD8(+) T cells overcome regulation by CD8(lo) T cells. These data define a novel peripheral regulatory CD8(+ )T cell population that arises after repeated antigen encounter in vivo. These cells have implications in the maintenance of tolerance and memory.

Adoptive Transfer↗
PubMed2006

Effect of blood transfusion on outcome after major burn injury: a multicenter study.

OBJECTIVE: To delineate blood transfusion practices and outcomes in patients with major burn injury. CONTEXT: Patients with major burn injury frequently require multiple blood transfusions; however, the effect of blood transfusion after major burn injury has had limited study. DESIGN: Multicenter retrospective cohort analysis. SETTING: Regional burn centers throughout the United States and Canada. PATIENT POPULATION: Patients admitted to a participating burn center from January 1 through December 31, 2002, with acute burn injuries of >or=20% total body surface area. OUTCOMES MEASURED: Outcome measurements included mortality, number of infections, length of stay, units of blood transfused in and out of the operating room, number of operations, and anticoagulant use. RESULTS: A total of 21 burn centers contributed data on 666 patients; 79% of patients survived and received a mean of 14 units of packed red blood cells during their hospitalization. Mortality was related to patient age, total body surface area burn, inhalation injury, number of units of blood transfused outside the operating room, and total number of transfusions. The number of infections per patient increased with each unit of blood transfused (odds ratio, 1.13; p<.001). Patients on anticoagulation during hospitalization received more blood than patients not on anticoagulation (16.3+/-1.5 vs. 12.3+/-1.5, p<.001). CONCLUSIONS: The number of transfusions received was associated with mortality and infectious episodes in patients with major burns even after factoring for indices of burn severity. The utilization of blood products in the treatment of major burn injury should be reserved for patients with a demonstrated physiologic need.

Adult↗
PubMed2006

The effect of burn injury on CD8+ and CD4+ T cells in an irradiation model of homeostatic proliferation.

BACKGROUND: Homeostatic proliferation of T cells has recently been shown to be an important mechanism in the host response to infection. However, its role in the T cell response to burn injury is unknown. In this study, we examine the effect of burn injury on CD4+ and CD8+ T cell homeostatic proliferation after irradiation. METHODS: Wild-type C57BL/6 female mice were irradiated with six grays ionizing radiation and 48 hours later, syngeneic whole splenocytes or purified CD4+ or CD8+ T cells labeled with carboxy-fluorescein diacetate, succinimidyl ester were adoptively transferred. Two days later, mice underwent a 20% burn injury, followed by splenocyte harvest 3 and 10 days after injury. RESULTS: Burn mice demonstrate increased splenic cellularity and CD8+ T cell proliferation after adoptive transfer of either purified CD8+ cells or whole spleen populations compared with unburned (sham) mice. In contrast, CD4+ T cell proliferation after burn injury is unchanged after adoptive transfer of whole spleen cells and drastically decreased after adoptive transfer of a purified CD4+ population compared with sham mice. Ten days after burn injury CD8+ T cells continue to demonstrate greater proliferation than CD4+ T cells. CONCLUSIONS: CD8+ T cells are more robust than CD4+ T cells in their proliferative response after burn injury. In addition, CD8+ T cell proliferation appears less reliant on other immune cells than purified CD4+ T cell proliferation. These data reiterate the importance of CD8+ T cells in the initial immune response to burn injury.

Adoptive Transfer↗
PubMed2005

Correction of factor IX deficiency in mice by embryonic stem cells differentiated in vitro.

Murine embryonic stem (ES) cells are pluripotent, but significant functional engraftment does not occur when they are introduced into the liver. However, here we demonstrate that functional liver engraftment does occur if the ES cells (from strain 129 mice) are first differentiated in vitro for 7 days in the presence of FGF. Strikingly, when these differentiated cells, termed putative endodermal precursors (PEPs), were injected into their livers, two of six C57BL/6 and four of eight BALB/c factor IX (F-IX)-deficient mice survived for >7 days, even though the recipients were of a different strain and, in the case of the BALB/c recipients, had a complete MHC mismatch. F-IX was detected in all six of the PEP-injected survivors. Two mice subsequently died of causes unrelated to F-IX; the others survived until death at 38 or 115 days after the transplantation. No uninjected control F-IX-deficient mice survived for >7 days. Large confluent regions of sinusoidal PEP engraftment were demonstrated by immunofluorescence in the long-term BALB/c survivors. The PEP engraftment was not associated with detectable cell fusion, and the transplantation was accompanied with only a low incidence of teratoma formation.

Animals↗
PubMed2005

Valdecoxib-associated acute generalized exanthematous pustulosis.

AGEP (acute generalized exanthematous pustulosis) is a relatively rare exfoliative skin syndrome consisting of generalized eruption of pustules in response to medication or infection. Because AGEP may have other systemic manifestations, such as renal failure, hyperthermia, lab abnormalities, and/or hemodynamic instability, it is important to make the distinction between AGEP and other life-threatening generalized skin diseases, such as toxic epidermal necrolysis (TEN). Here we present a case of AGEP in response to valdecoxib, which has not previously been described in the literature. The patient presented with profound hypotension requiring fluid and vasopressor support and was referred to the burn service for treatment of TEN, but her skin lesions were inconsistent with this diagnosis. A dermatology consult was obtained and suggested a diagnosis of AGEP, which a biopsy confirmed. TEN and AGEP present with similar history, types of associated drugs, and immunology. Both can be associated with antibiotics, non-steroidals, and anticonvulsants, but AGEP is more frequent with aminopenicillins, while TEN is associated more often with sulfonamide antibiotics. Both disorders have a proposed T cell-mediated immune response, but they differ in the mechanism. A description of valdecoxib and its role as a sulfonamide in producing cutaneous reactions is also provided.

Carpal Tunnel Syndrome↗
PubMed2005

Chest wall necrosis and death secondary to hydrochloric acid infusion for metabolic alkalosis.

Central line complications are common, and extravasation injuries related to infusion of caustic substances have been previously described. Although hydrochloric acid has been used for many years to treat metabolic alkalosis, there have been no reported fatal complications. We report the case of a 53-year-old female who received a fatal chemical burn due to extravasation from a subclavian central venous catheter of hydrochloric acid infused to correct severe metabolic alkalosis. This case illustrates the hazards of the infusion of caustic substances through central lines and underscores the importance of constant vigilance regarding line positioning and changes to the surrounding tissues when infusing these substances.

Alkalosis↗
PubMed2005

Multidisciplinary approach to abdominal wall reconstruction after decompressive laparotomy for abdominal compartment syndrome.

INTRODUCTION: Decompressive laparotomy for abdominal compartment syndrome has been shown to reduce mortality in critically ill patients, but little is known about the outcome of abdominal wall reconstruction. This study investigates the role of plastic surgeons in the management and reconstruction of these abdominal wall defects. METHODS: We performed a retrospective review of 82 consecutive critically ill patients who underwent decompressive laparotomy for abdominal compartment syndrome, at a university level 1 trauma center, from April 2000 to May 2004. Patients reconstructed by trauma surgeons alone (n = 15) were compared with patients reconstructed jointly with plastic surgeons (n = 12), using Student t test and chi analysis. RESULTS: Eighty-two patients underwent decompressive laparotomy for abdominal compartment syndrome, yielding 50 survivors (61%). Of the 27 patients who underwent abdominal wall reconstruction, 6 had early primary fascial repair, and 21 had staged reconstruction with primary fascial closure (n = 4), components separation alone (n = 3), components separation with mesh (n = 10), or permanent mesh only (n = 4). Compared with patients whose reconstruction was performed by trauma surgeons, patients who underwent a combined approach with plastic surgeons were older (50.5 versus 31.7 years, P < 0.05), had more comorbidities (P < 0.001), were less likely to have a traumatic etiology (P < 0.001), had a longer delay to reconstruction (407 versus 119 days, P < 0.05), and were more likely to undergo components separation (P < 0.05). Mean follow-up of 11.5 months revealed 2 recurrent hernias in the combined reconstruction group, both of which were successfully repaired. CONCLUSIONS: A multidisciplinary approach is essential to the successful management of abdominal wall defects after decompressive laparotomy for abdominal compartment syndrome. Although carefully selected patients can undergo early primary fascial repair, most of reconstructed patients had staged closure of the abdominal wall via components separation, with a low rate of recurrent hernia. High-risk patients with large defects and comorbidities appear to benefit from the involvement of a plastic surgeon.

Abdomen↗
PubMed2005

Superselective catheterization and embolization as first-line therapy for lower gastrointestinal bleeding.

Emergent operative intervention for lower gastrointestinal bleeding (LGIB) is associated with significant morbidity and mortality. Advances in endovascular techniques have made superselective catheterization and embolization (SSCE) of small visceral arterial branches possible. We hypothesized that SSCE for LGIB would be an effective first-line therapy and associated with low mortality. We identified all patients that underwent visceral angiography at our institution from 1997 to 2003. Records from all patients with documented LGIB and in whom SSCE was used as first-line therapy were reviewed. Twenty-three patients (69 +/- 11 years) were treated with SSCE as an initial intervention for LGIB. A definitive bleeding site was identified in 95 per cent of cases (22/23). Eleven patients (48%) developed an early complication [recurrent bleeding (n=5; two required surgery), asymptomatic ischemic colonic mucosa (n=3), acute renal insufficiency (n=1; resolved), and femoral pseudo-aneurysm (n=2; one treated operatively)]. Long-term (mean 19 months) follow-up was available for 17 patients. Five patients (22%) experienced recurrent LGIB, and three patients had evidence of colonic ischemic. One patient required endoscopic dilation of a stricture, and three underwent surgical resection. There was no mortality in our series. In this series, SSCE was an effective first-line therapy for LGIB. Rebleeding and ischemia rates were low.

Age Factors↗
PubMed2004

Real-time monitoring of keratin 5 expression during burn re-epithelialization.

BACKGROUND: Keratin is a major protein produced during epithelialization following burn injury and is a useful marker for assessing wound healing. Transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the keratin 5 (K5) promoter (K5GFP mice) were used to monitor keratin expression, and thus, re-epithelialization of burn wounds. MATERIALS AND METHODS: K5GFP transgenic mice were created using conventional techniques, with PCR and Southern blot confirmation of transgene incorporation, followed by selection of the line with the most intense and consistent basal epithelial EGFP expression. Epi-fluorescent microscopy of 24 K5GFP mouse flanks and 10 negative littermate controls was used to characterize EGFP intensity, before wounding and serially for 30 days after administration of a standardized burn wound and excision. Biopsy sections of K5GFP and negative control mice were stained with K5 antibody and imaged with confocal microscopy to characterize the distribution of EGFP and K5 at baseline and after injury and to examine the correlation between K5 expression and EGFP expression during healing. RESULTS: Green fluorescence intensity increased at the advancing wound margin of burned K5GFP mice, reaching a maximum between days 12 and 15 post-burn and then decreasing as healing completed. K5 and EGFP expression increased in parallel in burned K5GFP mice as demonstrated by confocal microscopy. CONCLUSION: EGFP expression correlated with K5 expression during wound healing and therefore serves as a good marker of re-epithelialization. This transgenic model allows noninvasive, real-time assessment of in vivo K5 expression and will be useful in the study of wound healing.

Animals↗
PubMed2004

Early enteral nutrition does not decrease hypermetabolism associated with burn injury.

BACKGROUND: A prospective, randomized study was performed to compare the effects of early versus late enteral feeding on postburn metabolism. METHODS: Burn patients were randomized to receive enteral feedings either within 24 hours (early) or 7 days (late) of injury. Basal energy expenditure (BEE) was calculated from Harris-Benedict equations and resting energy expenditure (REE) was obtained from indirect calorimetry. The average daily energy expenditure (DEE) was expressed as REE/BEE. RESULTS: Average age, burn size, infections, and length of stay were similar between groups. Mortality between groups was similar (early, 28%; late, 38%) and not significantly influenced by inhalation injury. When controlled for percentage of total body surface area burn, inhalation injury, and age, the early group had an increased rather than decreased DEE, with a mean DEE calorie 0.17 more than the late group (p = 0.07). CONCLUSION: Early enteral feeding does not decrease the average energy expenditure associated with burn injury.

Adult↗
PubMed2003

Induction of hepatic differentiation in embryonic stem cells by co-culture with embryonic cardiac mesoderm.

BACKGROUND: Modifications in vitro have been used to direct embryonic stem (ES) cells toward endodermal phenotypes including hepatocytes; however, developmental correlates and evidence of biologic activity is lacking, and critical cell-cell interactions have not been investigated. In this study, we hypothesized that cardiac mesoderm (CM) signals ES cells in co-culture to undergo differentiation toward early hepatocyte lineage as determined by morphology and induction of genes essential for endodermal competence and hepatocyte development. METHODS: Green fluorescent protein ES derived from A129 mice were cultured with or without embryonic chick cardiac mesoderm. Cultures from day 1, 2, and 4 were analyzed for colony formation and ES morphology and 10(6) ES-derived cells were isolated for mRNA analysis. RESULTS: ES in co-culture with CM displayed colony formation, polymorphic appearance, and definitive interface with CM. In addition, ES + CM co-culture activated crucial transcription factors (sox 17alpha, HNF3beta, and GATA 4) required for hepatocyte development by day 1. mRNA for albumin and especially a-fetoprotein were also increased by culture days 2 and 4. CONCLUSIONS: ES cells co-cultured with CM display morphology and gene expression pattern required for hepatocyte differentiation and appear to recapitulate the molecular events of hepatogenesis.

Albumins↗
PubMedDate not supplied

Eczema mimicking child abuse: a case of mistaken identity.

Many skin conditions can mimic child abuse by burning. Multidisciplinary evaluation of suspicious burns helps prevent both the underreporting and the misdiagnosis of child abuse by burning. We report a case of pediatric eczema mimicking an abusive burn.

Burns↗
PubMedDate not supplied

Educational opportunities for experienced staff: do they make a difference?

This study evaluates the impact of educational programs, such as Advanced Burn Life Support (ABLS), on the knowledge base of experienced burn nurses. A convenience sample of six clinical experts within a 21-bed southeastern burn center who had never taken ABLS participated. The quantitative findings display a high level of value and an increase in knowledge base. The results of this study suggest that nurses with high levels of experience will have an increase in knowledge and express value in continuing education curricula. Consequently, this study supports the necessity of educational programs for nurses with significant specialized experience.

Burns↗