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Anthony A Meyer

Publications and source records attributed to Anthony A Meyer.

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

Axillary lymph node count is lower after neoadjuvant chemotherapy.

BACKGROUND: Retrieval of fewer than 10 lymph nodes at axillary dissection (ALND) for breast cancer can represent anatomic variation or inadequate dissection. We postulated that despite aggressive ALND, a lower lymph node count is more frequent after neoadjuvant chemotherapy. METHODS: Patients who received neoadjuvant chemotherapy followed by ALND were compared with patients who received surgery first. All patients received a level I and II ALND at a single institution by one of the breast surgeons. The number of nodes retrieved at ALND was dichotomized into categories (< 10 and > or = 10), and compared using Fisher exact test. RESULTS: A total of 143 neoadjuvant and 170 surgery-first patients were studied. Patients treated with neoadjuvant chemotherapy were significantly more likely to have fewer than 10 lymph nodes retrieved at ALND than were the surgery-first patients (19/143 or 13% vs. 6/170 or 4%, P = .003). CONCLUSIONS: A low lymph node count is more common in patients after treatment with neoadjuvant chemotherapy and should not be assumed to represent an incomplete ALND.

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↗
PubMed2006

Increased Toll-like receptor 4 expression on T cells may be a mechanism for enhanced T cell response late after burn injury.

BACKGROUND: Burn injury is associated with a dynamic T cell response. We have previously reported an enhanced functional T cell response 14 days after burn injury. Toll-like receptors (TLR), primarily expressed on innate immune cells, have recently been identified on certain T cell subsets, including activated and memory T cells. Our hypothesis is that increased TLR4 expression on memory T cells may be a mechanism for enhanced T cell response 14 days after burn injury. METHODS: Splenocytes from wild-type C57Bl/6 mice were harvested 14 days after a 20% total body surface area (TBSA) scald burn or sham injury. Splenocytes ex vivo were surface stained either with monoclonal anti-CD3, anti-CD4, anti-CD8, or anti-CD44 antibodies or a two-step biotin-TLR4 monoclonal antibody-streptavidin-FITC surface stain and results analyzed by flow cytometry. RESULTS: TLR4 expression is successfully detected on CD4 and CD8 T cells. TLR4 expression is significantly (p < 0.05) increased on CD4 T cells and CD8 T cells 14 days after burn injury. There is a significant (p < 0.05) increase in CD44 (memory) CD4 and CD44 (memory) CD8 T cells 14 days after burn injury and this is associated with a significant (p < 0.05) increase of TLR4 expression in both T cell populations. CONCLUSIONS: This study demonstrates for the first time the potential role of TLR4 expression on memory T cells generated late after burn injury. Although further analysis is required, these data reiterate the importance of adaptive immunity and the complexity of the immune response to burn injury.

Animals↗
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

Psychologic well-being of surgery residents after inception of the 80-hour workweek: a multi-institutional study.

BACKGROUND: The 80-hour workweek was adopted by US residency programs on July 1, 2003. Our published data from the preceding year indicated significant impairment in psychologic well-being among surgery residents. The purpose of this study was to determine whether psychologic well-being and academic performance of surgery residents improved after inception of the 80-hour workweek. METHODS: A single-blinded survey of general surgery residents (n=130) across 4 US training programs was conducted after July 1, 2003, with the use of validated psychometric surveys (Symptom Checklist-90-R and Perceived Stress Scale) and the American Board of Surgery In-Training Examination; comparison was done with preceding year and societal data. Primary outcomes were "psychologic distress" and "perceived stress." Secondary outcomes were "somatization," "depression," "anxiety," "interpersonal sensitivity," "hostility," "obsessive-compulsive behavior," "phobic anxiety," "paranoid ideation," "psychoticism." and "academic performance." The impact of demographic variables was assessed. RESULTS: Mean psychologic distress improved from the preceding year (P < .01) but remained elevated, compared with societal norms (P < .001). The proportion of residents meeting the criteria for clinical psychologic distress (>or=90th percentile) decreased from 38% before, to 24% after, July 2003. Mean perceived stress remained elevated, compared with norms (P < .0001) without improvement from the preceding year. Overall academic performance was unchanged. Previously elevated secondary psychologic outcomes improved after July 2003 (P < .05), although obsessive-compulsive behavior, depression, interpersonal sensitivity, hostility, and anxiety failed to normalize. Male gender and single status were independent risk factors for psychologic distress. CONCLUSIONS: Inception of the 80-hour workweek is associated with reduced psychologic distress among surgery residents. The perception of stress and academic performance remains unchanged.

Adult↗
PubMed2005

Blood transfusion is an independent predictor of increased mortality in nonoperatively managed blunt hepatic and splenic injuries.

BACKGROUND: Management strategies for blunt solid viscus injuries often include blood transfusion. However, transfusion has previously been identified as an independent predictor of mortality in unselected trauma admissions. We hypothesized that transfusion would adversely affect mortality and outcome in patients presenting with blunt hepatic and splenic injuries after controlling for injury severity and degree of shock. METHODS: We retrospectively reviewed records from all adults with blunt hepatic and/or splenic injuries admitted to a Level I trauma center over a 4-year period. Demographics, physiologic variables, injury severity, and amount of blood transfused were analyzed. Univariate and multivariate analysis with logistic and linear regression were used to identify predictors of mortality and outcome. RESULTS: One hundred forty-three (45%) of 316 patients presenting with blunt hepatic and/or splenic injuries received blood transfusion within the first 24 hours. Two hundred thirty patients (72.8%) were selected for nonoperative management, of whom 75 (33%) required transfusion in the first 24 hours. Transfusion was an independent predictor of mortality in all patients (odds ratio [OR], 4.75; 95% confidence interval [CI], 1.37-16.4; p = 0.014) and in those managed nonoperatively (OR, 8.45; 95% CI, 1.95-36.53; p = 0.0043) after controlling for indices of shock and injury severity. The risk of death increased with each unit of packed red blood cells transfused (OR per unit, 1.16; 95% CI, 1.10-1.24; p < 0.0001). Blood transfusion was also an independent predictor of increased hospital length of stay (coefficient, 5.45; 95% CI, 1.64-9.25; p = 0.005). CONCLUSION: Blood transfusion is a strong independent predictor of mortality and hospital length of stay in patients with blunt liver and spleen injuries after controlling for indices of shock and injury severity. Transfusion-associated mortality risk was highest in the subset of patients managed nonoperatively. Prospective examination of transfusion practices in treatment algorithms of blunt hepatic and splenic injuries is warranted.

Adolescent↗
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

What do surgery residents do on their call nights?

BACKGROUND: Surgical resident education is entering a critical era of achieving core competencies despite work hour restrictions. An assessment of on-call activity is needed to maximize educational merit. METHODS: A time-motion study of resident on-call activity was performed at a university medical center and an urban affiliate hospital. Residents were followed by "shadow" residents who concurrently recorded resident activity. RESULTS: Activities of daily living and patient evaluation comprised the majority of on-call activity. Residents slept a median of 200 minutes per night. Cross-coverage activities accounted for 41% of pages and 19% of patient evaluation. Direct patient contact comprised only 7% of call night duties. Communication activity occupied 15% of total minutes, and a mean of 16 pages were received nightly. Significant differences in activities existed between resident levels and hospitals. CONCLUSIONS: Call activity consists primarily of activities of daily living, patient evaluation, and communication. Sleep accounts for nearly one third of all on-call activity. These data may be useful in improving both patient care and resident call experience.

After-Hours Care↗
PubMed2004

Psychological well-being of surgery residents before the 80-hour work week: a multiinstitutional study.

BACKGROUND: Accreditation Council on Graduate Medical Education work-hour restrictions are aimed at improving patient safety and resident well-being. Although surgical trainees will be dramatically affected by these changes, no comprehensive assessment of their well-being has been recently attempted. STUDY DESIGN: A multicenter study of psychological well-being of surgical residents (n = 108) across four US training programs before implementation of the 80-hour work week was performed using two validated surveys (Symptom Checklist-90-R [SCL-90-R] and Perceived Stress Scale [PSS]) during academic year 2002-03. Societal normative populations served as controls. Primary outcomes measures were psychologic distress (SCL-90-R) and perceived stress (PSS). Secondary outcomes measures (SCL-90-R) were somatization, depression, anxiety, interpersonal sensitivity, hostility, obsessive-compulsive behavior, phobic anxiety, paranoid ideation, and psychoticism. The impact of personal variables (age, gender, marital status) and programmatic variables (level of training, laboratory experience, institution) was assessed. RESULTS: Mean psychologic distress was significantly higher in general surgery residents than in the normative population (p < 0.0001), with 38% scoring above the 90th percentile and 72% above the 50th percentile. Mean perceived stress among surgery residents was higher than historic controls (p < 0.0001), with 21% scoring above the 90th percentile and 68% above the 50th percentile. Among secondary outcomes, eight of nine symptom dimensions were significantly higher in surgical residents than in societal controls. In subgroup analyses, male gender was associated with phobic anxiety (p < 0.001) and anxiety (p < 0.05), and junior level of training (PGY 1 to 3) with anxiety (p < 0.05), obsessive-compulsive behavior (p < 0.05), and interpersonal sensitivity (p < 0.05). CONCLUSIONS: More than one-third of general surgery residents meet criteria for clinical psychologic distress. Surgery residents perceive significantly more stress than societal controls. Both personal and programmatic variables likely affect resident well-being and should be considered in assessing the full impact of Accreditation Council on Graduate Medical Education directives and in guiding future restructuring efforts.

Adult↗
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

The effects of transforming growth factor-beta neutralization on postburn humoral immunity.

BACKGROUND: Burn injury induces immunosuppression, which is associated with an increased susceptibility to infection. Our laboratory has demonstrated that burn injury also impairs humoral immunity. We reported that burn injury enhanced expression of transforming growth factor-beta (TGF-beta) mRNA and that exogenous TGF-beta further impaired humoral immunity. The objective of this study was to clarify the role of TGF-beta on humoral immunity after burn injury with a neutralizing experiment. METHODS: Twelve BALB/c mice were randomly divided into two groups: sham and burn. Anesthetized mice received a 20% full-thickness burn or sham injury. The murine splenocytes containing 1.5 x 10 cells/mL were cultured with 2.5 microg/mL of lipopolysaccharide with or without 0.5 ng/mL of TGF-beta or 1 microg/mL of anti-TGF-beta neutralizing antibody, if necessary. Concentrations of immunoglobulin (Ig) M in the cell culture supernatant were determined by enzyme-linked immunosorbent assay and the number of IgM-secreting cells in the culture was measured by enzyme-linked immunospot assay. RESULTS: After 2-day culture, neutralization of TGF-beta dramatically restored IgM synthesis after burn injury. After 5-day culture, however, it restored IgM concentration but failed to restore a number of IgM-secreting cells. CONCLUSION: This neutralizing experiment demonstrated that TGF-beta is one of the inhibitors of IgM synthesis after burn injury. However, neutralization of TGF-beta was not enough to completely restore humoral immunity after burn injury. Investigation of the mechanism of impaired IgM synthesis after burn injury should be continued.

Animals↗
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↗
PubMed2003

Extracapsular extension of the sentinel lymph node metastasis: a predictor of nonsentinel node tumor burden.

OBJECTIVE: To identify predictors of nonsentinel node (NSN) tumor involvement in patients with a tumor-involved sentinel node (SN). SUMMARY BACKGROUND DATA: For many breast cancer patients who undergo intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL), the SN is the only tumor-involved axillary node. Associations between NSN tumor involvement and several clinical and histopathologic factors have been identified. The authors hypothesize that extracapsular extension (ECE) of the SN metastasis is highly predictive of NSN tumor involvement. METHODS: Between May 1998 and December 2001, 260 patients (263 cases) with clinical T1 or T2 (<5.0 cm) breast cancer underwent LM/SL at the University of North Carolina, using a combined blue dye and technetium sulfur colloid technique. In all cases with a tumor-involved SN, axillary lymph node dissection (ALND) was recommended. Statistical analysis, with Pearson chi-square tests, Fisher exact test, and multiple logistic regression, was performed. RESULTS: The SN contained tumor in 74 (28.1%) cases. ALND was performed in 70 of the 74 cases. ECE of the SN metastasis was present in 18 (25.7%) of the 70 cases. Patients with ECE of the SN metastasis were more likely to have NSN tumor involvement and had a greater total number of tumor-involved nodes than patients without ECE of the SN metastasis. Increasing size of the SN metastasis and increasing size of the primary tumor, examined as continuous variables, were associated with an increased likelihood of NSN tumor involvement on univariate analysis. However, only ECE of the SN metastasis was associated with NSN tumor involvement on multivariate analysis. CONCLUSIONS: ECE of the SN metastasis is a strong predictor of NSN tumor involvement. All patients with ECE of the SN metastasis should undergo mandatory completion ALND.

Adult↗