29 results on '"Duffner LA"'
Search Results
2. Estrogen mediates the sex difference in post-burn immunosuppression
- Author
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Gregory, MS, primary, Duffner, LA, additional, Faunce, DE, additional, and Kovacs, EJ, additional
- Published
- 2000
- Full Text
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Catalog
3. Social relationship factors, depressive symptoms, and incident dementia: a prospective cohort study into their interrelatedness.
- Author
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Duffner LA, Deckers K, Cadar D, de Vugt ME, and Köhler S
- Abstract
Background: Different aspects of social relationships (e.g., social network size or loneliness) have been associated with dementia risk, while their overlap and potentially underlying pathways remain largely unexplored. This study therefore aimed to (1) discriminate between different facets of social relationships by means of factor analysis, (2) examine their associations with dementia risk, and (3) assess mediation by depressive symptoms., Methods: Thirty-six items from questionnaires on social relationships administered in Wave 2 (2004/2005) of the English Longitudinal Study of Ageing ( n = 7536) were used for exploratory and confirmatory factor analysis. Factors were then used as predictors in Cox proportional hazard models with dementia until Wave 9 as outcome, adjusted for demographics and cardiovascular risk factors. Structural equation modeling tested mediation by depressive symptoms through effect decomposition., Results: Factor analyses identified six social factors. Across a median follow-up time of 11.8 years (IQR = 5.9-13.9 years), 501 people developed dementia. Higher factor scores for frequency and quality of contact with children (HR = 0.88; p = 0.021) and more frequent social activity engagement (HR = 0.84; p < 0.001) were associated with lower dementia risk. Likewise, higher factor scores for loneliness (HR = 1.13; p = 0.011) and negative experiences of social support (HR = 1.10; p = 0.047) were associated with higher dementia risk. Mediation analyses showed a significant partial effect mediation by depressive symptoms for all four factors. Additional analyses provided little evidence for reverse causation., Conclusions: Frequency and quality of social contacts, social activity engagement, and feelings of loneliness are associated with dementia risk and might be suitable targets for dementia prevention programs, partly by lowering depressive symptoms. more...
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- 2024
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4. Facing the Next "Geriatric Giant"-A Systematic Literature Review and Meta-Analysis of Interventions Tackling Loneliness and Social Isolation Among Older Adults.
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Duffner LA, Janssen N, Deckers K, Schroyen S, de Vugt ME, Köhler S, Adam S, Verhey FRJ, and Veenstra MY
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- Humans, Aged, Male, Female, Aged, 80 and over, Loneliness psychology, Social Isolation psychology
- Abstract
Objectives: Loneliness and social isolation are associated with adverse health outcomes, especially within the older adult population, underlining the need for effective interventions. This systematic review and meta-analysis aims to summarize all available evidence regarding the effectiveness of interventions for loneliness and social isolation, to map out their working mechanisms, and to give implications for policy and practice., Design: Systematic literature review and meta-analysis., Setting and Participants: Older adults (≥65 years)., Methods: A systematic search was conducted in MEDLINE, PsycINFO, and CINAHL for studies quantitively or qualitatively assessing effects of interventions for loneliness and social isolation in older adults, following predefined selection criteria. Risk of bias as well as small study effects were assessed and, wherever appropriate, information about effect sizes of individual studies pooled using random-effects meta-analyses. Sources for between-study heterogeneity were explored using meta-regression., Results: Of n = 2223 identified articles, n = 67 were eventually included for narrative synthesis. Significant intervention effects were reported for a proportion of studies (55.9% and 50.0% for loneliness and social isolation, respectively) and 57.6% of studies including a follow-up measure (n = 29) reported sustained intervention effects. Meta-analysis of n = 27 studies, representing n = 1756 participants, suggested a medium overall effect of loneliness interventions (d = -0.47; 95% CI, -0.62 to -0.32). Between-study heterogeneity was substantial and could not be explained by differences in study design, year of publication, outcome measures, intervention length, participant demographics, setting, baseline level of loneliness, or geographic location. However, non-technology-based interventions reported larger effect sizes on average (Δd = -0.35; 95% CI, -0.66 to -0.04; P = .029) and were more often significant. Qualitative assessment of potential intervention mechanisms resulted in 3 clusters of effective components: "promoting social contact," "transferring knowledge and skills," and "addressing social cognition"., Conclusions and Implications: Interventions for loneliness and social isolation can generally be effective, although some unexplained between-study heterogeneity remains. Further research is needed regarding the applicability of interventions across different settings and countries, also considering their cost-effectiveness., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) more...
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- 2024
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5. Dysphagia outcomes in COVID-19 patients: experiences in long-term acute care hospital (LTACH).
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Rajski B, Furey V, Nguyen A, Duffner LA, Young B, and Husain IA
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- Humans, Retrospective Studies, Hospitalization, Hospitals, Deglutition Disorders etiology, Deglutition Disorders therapy, COVID-19 complications
- Abstract
Purpose: Long term acute care hospitals (LTACHs) saw a significant increase in COVID-19 patients with prolonged acute illness recovery. Speech language pathologists (SLP) in LTACHs were integral in assessing swallowing and providing rehabilitation for dysphagia, however, there is limited research on LTACHs and dysphagia. Our aim was to describe this unique dysphagia management experience to improve future patient care., Methods: Retrospective chart reviews were conducted for patients admitted to RML Specialty Hospital for respiratory failure secondary to COVID-19 from April 1, 2020 to October 31, 2021. Demographic information, videofluoroscopic swallow study (VFSS) reports with Penetration and Aspiration Scale (PAS) scores and SLP notes were reviewed. Descriptive statistics and chi-square analysis were performed., Results: A total of 213 patients met inclusion criteria. Most patients presented with tracheostomy (93.9%) and were NPO (92.5%) on admission. A strong correlation (p = 0.029) was noted between dependence on mechanical ventilation and significant airway invasion, as indicated by PAS score of 7 or 8 on VFSS. There was a strong association (p = 0.001) between patients who had tracheostomy placed within 33 days of VFSS and recommendation for thin liquids. Upon discharge, the majority of patients (83.57%) transitioned successfully to oral diets, however, a strong association (p = 0.009) between higher age (≥ 62) and NPO at discharge was demonstrated., Conclusion: Patients admitted post COVID-19 to LTACH, especially those requiring tracheostomy, demonstrated various degrees of dysphagia and benefited from SLP intervention and instrumental swallow assessments. Most patients admitted to LTACH for COVID-19 were successfully rehabilitated for dysphagia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...
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- 2023
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6. Associations between social health factors, cognitive activity and neurostructural markers for brain health - A systematic literature review and meta-analysis.
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Duffner LA, DeJong NR, Jansen JFA, Backes WH, de Vugt M, Deckers K, and Köhler S
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- Humans, Prospective Studies, Cognition, Brain, Hippocampus
- Abstract
Social health factors (e.g., social activities or social support) and cognitive activity engagement have been associated with dementia risk, but their neural substrates have not been well established. This systematic review and meta-analysis summarizes the available evidence regarding the association between these factors and cerebral macro- and micro-structure. A comprehensive literature search was conducted in various databases, following predefined criteria. Heterogeneity, risk of publication bias and overall certainty of evidence were assessed using standardized scales and, whenever appropriate, random effects meta-analysis was conducted. Of 6715 identified articles, 43 were included. Overall, consistency of findings was low and methodological heterogeneity high for all outcomes. However, in some studies cognitive and social activities were positively associated with total brain, global and cortical grey matter and hippocampal volume as well as white matter microstructural integrity. Furthermore, structural social network characteristics (e.g., social network size) were associated with regional grey matter volumes, while functional social network characteristics (e.g., social support) were additionally associated with total brain volume. Meta-analyses revealed small but significant partial correlations between cognitive and social activities and hippocampal (three studies; n = 892; r
z =0.07) and white matter hyperintensity volume (three studies; n = 2934; rz =-0.04). More prospective studies are needed to assess temporal associations., Competing Interests: Declaration of Competing Interest The authors declare to not have any conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) more...- Published
- 2023
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7. The role of cognitive and social leisure activities in dementia risk: assessing longitudinal associations of modifiable and non-modifiable risk factors.
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Duffner LA, Deckers K, Cadar D, Steptoe A, de Vugt M, and Köhler S
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- Cognition, Humans, Longitudinal Studies, Risk Factors, Dementia epidemiology, Leisure Activities
- Abstract
Aims: With the projected surge in global dementia cases and no curative treatment available, research is increasingly focusing on lifestyle factors as preventive measures. Social and cognitive leisure activities are promising targets, but it is unclear which types of activities are more beneficial. This study investigated the individual and joint contribution of cognitive and social leisure activities to dementia risk and whether they modify the risks associated with other potentially modifiable and non-modifiable risk factors., Methods: We used data from the English Longitudinal Study of Ageing (ELSA) from 7917 participants, followed up from 2008/2009 (Wave 4) until 2018/2019 (Wave 9) for incident dementia. Self-reported baseline cognitive activities (e.g. 'reading the newspaper'), the number of social memberships (e.g. being a member of a social club) and social participation (e.g. 'going to the cinema') were clustered into high and low based on a median split. Subsequently, their individual and joint contribution to dementia risk, as well as their interaction with other dementia risk factors, were assessed with Cox regression models, adjusting for age, sex, level of education, wealth and a composite score of 11 lifestyle-related dementia risk factors., Results: After a median follow-up period of 9.8 years, the dementia incidence rate was 54.5 cases per 10.000 person-years (95% CI 49.0-60.8). Adjusting for demographic and other lifestyle-related risk factors, higher engagement in cognitive activities (HR = 0.58; 95% CI 0.40-0.84), a greater number of social memberships (HR = 0.65; 95% CI 0.51-0.84) and more social participation (HR = 0.71; 95% CI 0.54-0.95) were associated with lower dementia risk. In a joint model, only engagement in cognitive activities (HR = 0.60; 95% CI 0.40-0.91) and social memberships (HR = 0.75; 95% CI 0.56-0.99) independently explained dementia risk. We did not find any interaction with other modifiable and non-modifiable risk factors., Conclusions: Engagement in cognitive and social leisure activities may be beneficial for overall dementia risk, independent of each other and other risk factors. Both types of activities may be potential targets for dementia prevention measures and health advice initiatives. more...
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- 2022
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8. Long-Term Outcome after Prolonged Mechanical Ventilation. A Long-Term Acute-Care Hospital Study.
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Jubran A, Grant BJB, Duffner LA, Collins EG, Lanuza DM, Hoffman LA, and Tobin MJ
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- Aged, Female, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Time Factors, Critical Care Nursing methods, Critical Care Nursing statistics & numerical data, Respiration, Artificial nursing, Respiration, Artificial statistics & numerical data, Ventilator Weaning statistics & numerical data
- Abstract
Rationale: Patients managed at a long-term acute-care hospital (LTACH) for weaning from prolonged mechanical ventilation are at risk for profound muscle weakness and disability. Objectives: To investigate effects of prolonged ventilation on survival, muscle function, and its impact on quality of life at 6 and 12 months after LTACH discharge. Methods: This was a prospective, longitudinal study conducted in 315 patients being weaned from prolonged ventilation at an LTACH. Measurements and Main Results: At discharge, 53.7% of patients were detached from the ventilator and 1-year survival was 66.9%. On enrollment, maximum inspiratory pressure (Pi
max ) was 41.3 (95% confidence interval, 39.4-43.2) cm H2 O (53.1% predicted), whereas handgrip strength was 16.4 (95% confidence interval, 14.4-18.7) kPa (21.5% predicted). At discharge, Pimax did not change, whereas handgrip strength increased by 34.8% ( P < 0.001). Between discharge and 6 months, handgrip strength increased 6.2 times more than did Pimax . Between discharge and 6 months, Katz activities-of-daily-living summary score improved by 64.4%; improvement in Katz summary score was related to improvement in handgrip strength ( r = -0.51; P < 0.001). By 12 months, physical summary score and mental summary score of 36-item Short-Form Survey returned to preillness values. When asked, 84.7% of survivors indicated willingness to undergo mechanical ventilation again. Conclusions: Among patients receiving prolonged mechanical ventilation at an LTACH, 53.7% were detached from the ventilator at discharge and 1-year survival was 66.9%. Respiratory strength was well maintained, whereas peripheral strength was severely impaired throughout hospitalization. Six months after discharge, improvement in muscle function enabled patients to perform daily activities, and 84.7% indicated willingness to undergo mechanical ventilation again. more...- Published
- 2019
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9. Effect of pressure support vs unassisted breathing through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical ventilation: a randomized trial.
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Jubran A, Grant BJ, Duffner LA, Collins EG, Lanuza DM, Hoffman LA, and Tobin MJ
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- Aged, Female, Humans, Long-Term Care, Male, Middle Aged, Respiration, Survival Analysis, Time Factors, Treatment Outcome, Positive-Pressure Respiration methods, Tracheostomy instrumentation, Ventilator Weaning methods
- Abstract
Importance: Patients requiring prolonged mechanical ventilation (>21 days) are commonly weaned at long-term acute care hospitals (LTACHs). The most effective method of weaning such patients has not been investigated., Objective: To compare weaning duration with pressure support vs unassisted breathing through a tracheostomy collar in patients transferred to an LTACH for weaning from prolonged ventilation., Design, Setting, and Participants: Between 2000 and 2010, a randomized study was conducted in tracheotomized patients transferred to a single LTACH for weaning from prolonged ventilation. Of 500 patients who underwent a 5-day screening procedure, 316 did not tolerate the procedure and were randomly assigned to receive weaning with pressure support (n = 155) or a tracheostomy collar (n = 161). Survival at 6- and 12-month time points was also determined., Main Outcome Measure: Primary outcome was weaning duration. Secondary outcome was survival at 6 and 12 months after enrollment., Results: Of 316 patients, 4 were withdrawn and not included in analysis. Of 152 patients in the pressure-support group, 68 (44.7%) were weaned; 22 (14.5%) died. Of 160 patients in the tracheostomy collar group, 85 (53.1%) were weaned; 16 (10.0%) died. Median weaning time was shorter with tracheostomy collar use (15 days; interquartile range [IQR], 8-25) than with pressure support (19 days; IQR, 12-31), P = .004. The hazard ratio (HR) for successful weaning rate was higher with tracheostomy collar use than with pressure support (HR, 1.43; 95% CI, 1.03-1.98; P = .033) after adjusting for baseline clinical covariates. Use of the tracheostomy collar achieved faster weaning than did pressure support among patients who did not tolerate the screening procedure between 12 and 120 hours (HR, 3.33; 95% CI, 1.44-7.70; P = .005), whereas weaning time was equivalent with the 2 methods in patients who did not tolerate the screening procedure within 0 to 12 hours. Mortality was equivalent in the pressure-support and tracheostomy collar groups at 6 months (55.92% vs 51.25%; 4.67% difference, 95% CI, -6.4% to 15.7%) and at 12 months (66.45% vs 60.00%; 6.45% difference, 95% CI, -4.2% to 17.1%)., Conclusion and Relevance: Among patients requiring prolonged mechanical ventilation and treated at a single long-term care facility, unassisted breathing through a tracheostomy, compared with pressure support, resulted in shorter median weaning time, although weaning mode had no effect on survival at 6 and 12 months., Trial Registration: clinicaltrials.gov Identifier: NCT01541462. more...
- Published
- 2013
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10. Post-traumatic stress disorder after weaning from prolonged mechanical ventilation.
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Jubran A, Lawm G, Duffner LA, Collins EG, Lanuza DM, Hoffman LA, and Tobin MJ
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- Aged, Female, Humans, Male, Middle Aged, Prospective Studies, Time Factors, Respiration, Artificial adverse effects, Stress Disorders, Post-Traumatic etiology, Ventilator Weaning
- Abstract
Purpose: Weaning from prolonged mechanical ventilation may be associated with mental discomfort. It is not known whether such discomfort is linked with the development of post-traumatic stress disorder (PTSD). Accordingly, we investigated whether PTSD occurs in patients after weaning from prolonged ventilation. We also determined whether administering a questionnaire would identify patients at risk for developing PTSD., Methods: A prospective longitudinal study of patients transferred to a long-term acute-care hospital for weaning from prolonged ventilation was undertaken: 72 patients were studied 1 week after weaning, and 41 patients were studied again 3 months later. An experienced psychologist conducted a structured clinical interview 3 months after weaning to establish a diagnosis of PTSD. To assess for the presence of PTSD-related symptoms, the post-traumatic stress syndrome (PTSS-10) questionnaire was administered 1 week after weaning and 3 months later., Results: The psychologist diagnosed PTSD in 12% of patients 3 months after ventilator weaning. Patients who developed PTSD were more likely to have a previous history of psychiatric disorders (P < 0.02). A PTSS-10 score >20 one week after weaning reliably identified patients who were diagnosed with PTSD 3 months later: sensitivity 1.0; specificity 0.76; area under the receiver-operating characteristic curve 0.91., Conclusion: PTSD was diagnosed in 12% of patients who were weaned from prolonged ventilation. A PTSS-10 score >20 one week after weaning identified patients diagnosed with PTSD 3 months later. This finding suggests that a simple questionnaire administered before hospital discharge can identify patients at risk for developing PTSD. more...
- Published
- 2010
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11. Depressive disorders during weaning from prolonged mechanical ventilation.
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Jubran A, Lawm G, Kelly J, Duffner LA, Gungor G, Collins EG, Lanuza DM, Hoffman LA, and Tobin MJ
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- Aged, Aged, 80 and over, Comorbidity, Depressive Disorder diagnosis, Female, Humans, Length of Stay, Male, Mental Status Schedule, Middle Aged, Multivariate Analysis, Prevalence, Prospective Studies, Respiration, Artificial methods, Severity of Illness Index, Survival Analysis, Treatment Failure, Ventilator Weaning methods, Depressive Disorder etiology, Respiration, Artificial psychology, Ventilator Weaning psychology
- Abstract
Purpose: Patients who require mechanical ventilation are at risk of emotional stress because of total dependence on a machine for breathing. The stress may negatively impact ventilator weaning and survival. The purpose of this study was to determine whether depressive disorders in patients being weaned from prolonged mechanical ventilation are linked to weaning failure and decreased survival., Methods: A prospective study of 478 consecutive patients transferred to a long-term acute care hospital for weaning from prolonged ventilation was undertaken. A clinical psychologist conducted a psychiatric interview to assess for the presence of depressive disorders., Results: Of the 478 patients, 142 had persistent coma or delirium and were unable to be evaluated for depressive disorders. Of the remaining 336 patients, 142 (42%) were diagnosed with depressive disorders. In multivariate analysis, co-morbidity score [odds ratio (OR), 1.23; P = 0.007], functional dependence before the acute illness (OR, 1.70, P = 0.03) and history of psychiatric disorders (OR, 3.04, P = 0.0001) were independent predictors of depressive disorders. The rate of weaning failure was higher in patients with depressive disorders than in those without such disorders (61 vs. 33%, P = 0.0001), as was mortality (24 vs. 10%, P = 0.0008). The presence of depressive disorders was independently associated with mortality (OR, 4.3; P = 0.0002); age (OR, 1.06; P = 0.001) and co-morbidity score (OR, 1.24; P = 0.02) also predicted mortality., Conclusion: Depressive disorders were diagnosed in 42% of patients who were being weaned from prolonged ventilation. Patients with depressive disorders were more likely to experience weaning failure and death. more...
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- 2010
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12. Immunosuppression after injury in aged mice is associated with a TH1-TH2 shift, which can be restored by estrogen treatment.
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Kovacs EJ, Duffner LA, and Plackett TP
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- Animals, Female, Immune Tolerance drug effects, Interferon-gamma metabolism, Interleukin-4 metabolism, Mice, Mice, Inbred BALB C, Th1 Cells drug effects, Th1 Cells metabolism, Th2 Cells drug effects, Th2 Cells metabolism, Aging immunology, Burns immunology, Estrogens pharmacology, Immune Tolerance immunology, Th1 Cells immunology, Th2 Cells immunology
- Abstract
Aged mice are less likely to survive following traumatic injury and are more immunosuppressed than young mice who sustain comparable injuries. Immunosuppression in severely injured patients is associated with a TH1-TH2 shift. Young mice had robust delayed-type hypersensitivity (DTH) responses after receiving scald or sham injury, whereas the response was diminished in aged sham-injured mice (P < 0.05), and completely absent in aged burn-injured mice (P < 0.01). Production of interferon-gamma (IFN-gamma) did not differ between splenocytes from sham-injured young and aged mice. Splenocytes from burn-injured young and aged mice yielded similar (63-68%) decreases in IFN-gamma, relative to sham-injured mice (P < 0.05). In the absence of injury, cells from aged mice produced 2-fold more interleukin-4 (IL-4) than cells from young (P < 0.01). Interestingly, after burn, less IL-4 was produced by cell from young and aged mice, when compared to age-matched sham-injured animals (P < 0.05). Further studies revealed that estrogen replacement in aged mice restored the post-injury DTH responses (P < 0.05). Interestingly, this restoration paralleled a recovery in IFN-gamma production by splenocytes, but not IL-4 production. Additional studies will be required to determine if age-specific therapies are needed for the treatment of all trauma patients. more...
- Published
- 2004
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13. Effect of acute ethanol exposure on the dermal inflammatory response after burn injury.
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Faunce DE, Garner JL, Llanas JN, Patel PJ, Gregory MS, Duffner LA, Gamelli RL, and Kovacs EJ
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- Animals, Burns immunology, Burns microbiology, Burns mortality, Inflammation etiology, Inflammation immunology, Inflammation microbiology, Inflammation pathology, Male, Mice, Neutrophil Infiltration drug effects, Pseudomonas Infections mortality, Pseudomonas Infections pathology, Skin immunology, Skin metabolism, Skin microbiology, Tumor Necrosis Factor-alpha biosynthesis, Tumor Necrosis Factor-alpha physiology, Burns pathology, Ethanol administration & dosage, Skin pathology
- Abstract
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. more...
- Published
- 2003
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14. Survival and cell mediated immunity after burn injury in aged mice.
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Kovacs EJ, Grabowski KA, Duffner LA, Plackett TP, and Gregory MS
- Abstract
The elderly are less able to survive burn injury than young healthy individuals. Regardless of age, burn victims often succumb to secondary infections rather than the primary injury. Since immune responses diminish with age, it is likely that aged individuals are predisposed to a poor outcome by virtue of their weak immune system. Elevated production of macrophage-derived mediators, including interleukin-6 (IL-6), may lead to post-injury immunosuppression in young adults. Healthy aged individuals produce high circulating levels of these mediators; therefore, the combination of the age and burn trauma could further suppress immune responses and contribute to the rapid demise of aged burn patients. Herein, the effects of age and burn trauma using a murine scald injury model were examined. After injury, aged mice are less likely to survive, are unable to mount immune responses, and produce more IL-6 when compared to young adult mice given the same size injuries. Enhancing our understanding of the mechanisms responsible for regulating cell-mediated immune responses after injury could lead to the development of therapies designed to treat aged burn patients. more...
- Published
- 2002
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15. Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice.
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Low QE, Drugea IA, Duffner LA, Quinn DG, Cook DN, Rollins BJ, Kovacs EJ, and DiPietro LA
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- Animals, Chemokine CCL2 deficiency, Chemokine CCL2 genetics, Chemokine CCL3, Chemokine CCL4, Collagen biosynthesis, Epithelial Cells pathology, Epithelial Cells physiology, Macrophage Inflammatory Proteins deficiency, Macrophage Inflammatory Proteins genetics, Macrophages pathology, Macrophages physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Physiologic, Skin pathology, Time Factors, Wound Healing genetics, Wounds and Injuries pathology, Chemokine CCL2 physiology, Macrophage Inflammatory Proteins physiology, Wound Healing physiology
- Abstract
A salient feature of normal wound healing is the development and resolution of an acute inflammatory response. Although much is known about the function of inflammatory cells within wounds, little is known about the chemotactic and activation signals that influence this response. As the CC chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemotactic protein-1 (MCP-1) are abundant in acute wounds, wound repair was examined in MIP-1alpha(-/-) and MCP-1(-/-) mice. Surprisingly, wound re-epithelialization, angiogenesis, and collagen synthesis in MIP-1alpha(-/-) mice was nearly identical to wild-type controls. In contrast, MCP-1(-/-) mice displayed significantly delayed wound re-epithelialization, with the greatest delay at day 3 after injury (28 +/- 5% versus 79 +/- 14% re-epithelialization, P < 0.005). Wound angiogenesis was also delayed in MCP-1(-/-) mice, with a 48% reduction in capillary density at day 5 after injury. Collagen synthesis was impeded as well, with the wounds of MCP-1(-/-) mice containing significantly less hydroxyproline than those of control mice (25 +/- 3 versus 50 +/- 8 microg/wound at day 5, P < 0.0001). No change in the number of wound macrophages was observed in MCP-1(-/-) mice, suggesting that monocyte recruitment into wounds is independent of this chemokine. The data suggest that MCP-1 plays a critical role in healing wounds, most likely by influencing the effector state of macrophages and other cell types. more...
- Published
- 2001
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16. Evidence of oxidative injury during aging of the liver in a mouse model.
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Colantoni A, Idilman R, de Maria N, Duffner LA, Van Thiel DH, Witte PL, and Kovacs EJ
- Abstract
The aim of the present study was to determine whether oxidative stress contributes to aging of the liver in a mouse model. Liver was obtained from young (3-5 months old) and aged (18-24 months old) mice. No age-induced gross changes in liver morphology were detected by light microscopy. Apoptosis was measured using the fragment end labeling of DNA for the immunohistochemical identification of the apoptotic nuclei. The total apoptotic cells represented 1% of the total cells in livers of young mice and 8% in those of aged mice. Among the total apoptotic cells in livers of aged animals, 15% were hepatocytes, 40% sinusoidal endothelial cells, and 45% bile duct cells. Hepatic lipid peroxidation, expressed as malonaldehyde levels, protein oxidation, measured by protein carbonyl content, and DNA oxidation, measured as 8-hydroxy-2'-deoxyguanosine (oxo(8)dG), were significantly increased in the livers of aged animals as compared to younger mice. The apoptotic cells presented elevated levels of oxidized DNA, detected by immunohistochemistry using an antibody directed against oxo(8)dG in serial sections. These results suggest that livers of aged animals presents evidence of increased oxidative injury and apoptosis. Because the apoptotic cells in the aged livers are mostly bile duct cells and sinusoidal endothelial cells, the cells most sensitive to oxidative stress injury, it can be hypothesized that reactive oxygen species-induced apoptosis in these cells contributes to the aging of the liver. more...
- Published
- 2001
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17. Differential production of prostaglandin E(2) in male and female mice subjected to thermal injury contributes to the gender difference in immune function: possible role for 15-hydroxyprostaglandin dehydrogenase.
- Author
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Gregory MS, Duffner LA, Hahn EL, Tai HH, Faunce DE, and Kovacs EJ
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- Animals, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Burns metabolism, Cell Division drug effects, Cells, Cultured, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors pharmacology, Dinitrofluorobenzene administration & dosage, Dinitrofluorobenzene immunology, Dinoprostone biosynthesis, Dinoprostone pharmacology, Female, Hypersensitivity, Delayed immunology, Indomethacin pharmacology, Irritants administration & dosage, Irritants immunology, Isoenzymes metabolism, Lung metabolism, Macrophages drug effects, Macrophages metabolism, Male, Mice, Mice, Inbred BALB C, Prostaglandin-Endoperoxide Synthases metabolism, Sex Characteristics, Spleen cytology, Burns immunology, Dinoprostone immunology, Hydroxyprostaglandin Dehydrogenases biosynthesis
- Abstract
We have previously reported a macrophage-mediated gender difference in postburn immunosuppression, which was dependent upon elevated levels of circulating 17beta-estradiol (E(2)) and, in part, interleukin-6. Herein we examined the role of prostaglandin E(2) (PGE(2)), a potent suppressor of cell-mediated immunity. Circulating levels of PGE(2) were significantly elevated in females but not males at 10 days postburn (P < 0.01), and indomethacin treatment fully restored the delayed-type hypersensitivity and splenocyte proliferative responses of thermally injured females. While there was no difference in cyclooxygenase-2 protein expression in the lungs and liver of thermally injured male and female mice, there was a marked decrease in the protein expression of 15-hydroxyprostaglandin dehydrogenase in females. These data demonstrate that PGE(2) is a critical mediator of immunosuppression in thermally injured female mice and that the increase in circulating PGE(2) is derived, in part, from decreased degradation and clearance of PGE(2)., (Copyright 2000 Academic Press.) more...
- Published
- 2000
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18. The role of interleukin 6 in interferon-gamma production in thermally injured mice.
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Durbin EA, Gregory MS, Messingham KA, Fontanilla CV, Duffner LA, and Kovacs EJ
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- Animals, Cells, Cultured, Concanavalin A pharmacology, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Interleukin-4 biosynthesis, Interleukin-6 metabolism, Leukocytes metabolism, Lipopolysaccharides pharmacology, Macrophages metabolism, Mice, Mice, Inbred BALB C, Microscopy, Fluorescence, Spleen cytology, Temperature, Interferon-gamma biosynthesis, Interleukin-6 physiology
- Abstract
Following traumatic injury, patients suffer from compromised immunity increasing their susceptibility to infection. Previous studies from this laboratory demonstrated that female BALB/c mice subjected to a 15% total body surface area (TBSA) scald injury exhibit a decrease in cell-mediated immunity 10 days post-burn. Studies described herein revealed that concanavalin A (Con A; 2 microg/ml)-stimulated splenocytes from sham treated animals produced 3557+/-853 pg/ml of IFN-gamma while splenocytes from burn injured animals released two-fold more cytokine (P<0.05). To determine whether leukocyte production of IFN-gamma was under the influence of macrophages, splenic macrophage supernatants generated from burned animals were incubated with splenic lymphocytes from sham and burn animals. The amount of IFN-gamma released by lymphocytes from sham animals increased when cultured with macrophages from burned mice (P<0.05). This suggests that the increase in IFN-gamma production by unfractionated splenocytes in burned mice relative to sham treated animals is macrophage-dependent. Macrophage supernatants from burned mice released twice as much IL-6 as supernatants from sham animals (P<0.05), and when IL-6 was blocked in vivo, the amount of IFN-gamma production in burned mice decreased to sham levels (P<0.05). Thus, IL-6 mediates IFN-gamma production following burn., (Copyright 2000 Academic Press.) more...
- Published
- 2000
- Full Text
- View/download PDF
19. Dose-dependent effect of ethanol on hepatic oxidative stress and interleukin-6 production after burn injury in the mouse.
- Author
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Colantoni A, Duffner LA, De Maria N, Fontanilla CV, Messingham KA, Van Thiel DH, and Kovacs EJ
- Subjects
- Animals, Burns immunology, Central Nervous System Depressants blood, Dose-Response Relationship, Drug, Ethanol blood, Interleukin-6 immunology, Liver immunology, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Oxidative Stress physiology, Reactive Oxygen Species immunology, Reactive Oxygen Species metabolism, Burns metabolism, Central Nervous System Depressants administration & dosage, Ethanol administration & dosage, Interleukin-6 metabolism, Liver drug effects, Oxidative Stress drug effects
- Abstract
Background: Burned patients with detectable blood alcohol levels (BAL) show an elevated mortality rate. Interleukin (IL)-6 and reactive oxygen species (ROS) production is stimulated independently by alcohol and burn injury. The aim of the study was to determine whether increasing levels of alcohol differentially enhance the hepatic production of IL-6 and ROS after burn in a murine model of dorsal scald injury. Groups of mice received either saline or alcohol intraperitoneally to reach a BAL of 100 mg/dl or 300 mg/dl at the time of burn (15% total body surface scald) or sham injury., Results: Burn injury alone resulted in a low mortality rate at 24 hr after injury as did the burn group with a BAL of 100 mg/dl (15%), whereas 57% of the mice burned with a BAL of 300 mg/dl did not survive (p = 0.02). Twenty-four hours after burn or sham injury, IL-6 levels were measured by enzyme-linked immunosorbent assay in serum and liver. In the saline-treated group, IL-6 circulating and hepatic levels rose after burn injury (p < 0.03). Circulating IL-6 levels in sham mice increased 1.5-fold in the group with a BAL of 100 mg/dl and 3-fold in those with a BAL of 300 mg/ml (p = 0.005 versus burn-injured, saline-treated). IL-6 hepatic production after burn injury was higher in the mice with a BAL of 300 mg/dl than in those with a BAL of 100 mg/dl and the saline-treated group (p = 0.001). Among the burned mice, alcohol exposure increased hepatic ROS production, measured by lipid peroxidation and protein oxidation, in a dose-dependent manner., Conclusions: Alcohol enhances in a dose-dependent manner the hepatic production of IL-6 induced by burn injury through the modulation of oxidative stress. The increased mortality rate of mice exposed to alcohol and burn injury may be due to the adverse effect on immune function induced by IL-6 elevation. more...
- Published
- 2000
20. Anti-interleukin-6 antibody treatment restores cell-mediated immune function in mice with acute ethanol exposure before burn trauma.
- Author
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Fontanilla CV, Faunce DE, Gregory MS, Messingham KA, Durbin EA, Duffner LA, and Kovacs EJ
- Subjects
- Animals, Antibodies therapeutic use, Burns drug therapy, Hypersensitivity, Delayed drug therapy, Immune Tolerance, Interleukin-6 immunology, Male, Mice, Mice, Inbred C57BL, Spleen cytology, Spleen drug effects, Antibodies pharmacology, Burns immunology, Central Nervous System Depressants pharmacology, Ethanol pharmacology, Hypersensitivity, Delayed immunology, Immunity, Cellular immunology, Interleukin-6 antagonists & inhibitors
- Abstract
Background: Previous studies from this laboratory reported that suppression of cell-mediated immune function was coincident with elevated interleukin (IL)-6 production after acute ethanol exposure before burn trauma, compared with either insult alone. The goal of this study was to investigate whether treatment with an anti-IL-6 antibody could restore immunocompetence in mice subjected to burn trauma with previous exposure to alcohol, as assessed by delayed-type hypersensitivity (DTH) and mitogen-induced splenocyte proliferative responses., Methods: Mice given an ethanol treatment designed to reach a blood alcohol level of 100 mg/dl before a 15% total body surface area burn injury were treated with an anti-IL-6 antibody at 30 min and 24 hr postinjury., Results: Burn/ethanol mice exhibited a 91% suppression of the DTH response ( < 0.01) and a 76% suppression of mitogen-induced splenocyte proliferation (p < 0.01) at 48 hr postinjury, along with increased levels of circulating and splenic macrophage-derived IL-6, compared with all other treatment groups. After anti-IL-6 antibody administration to burn/ethanol mice, there was a 25% (p < 0.05) and 63% (p < 0.01) recovery of the DTH and splenocyte proliferative responses, respectively. Addition of exogenous IL-6 to splenocyte cultures isolated from anti-IL-6 antibody-treated burn/ethanol mice resulted in a 70% inhibition of mitogen-induced proliferative responses (p < 0.03)., Conclusions: These data confirm previous findings that burn in combination with acute ethanol exposure suppresses cell-mediated immune function compared with either insult alone. Furthermore, the ability of the anti-IL-6 antibody treatment to improve cellular immune responses in the burn/ethanol group suggests that blocking this cytokine may be beneficial for the ethanol-exposed, thermally injured individual. more...
- Published
- 2000
21. Cellular immunity after ethanol exposure and burn injury: dose and time dependence.
- Author
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Messingham KA, Fontanilla CV, Colantoni A, Duffner LA, and Kovacs EJ
- Subjects
- Animals, Apoptosis, Cell Division, Ethanol blood, Hypersensitivity, Delayed, Interleukin-6 biosynthesis, Interleukin-6 blood, Macrophages metabolism, Male, Mice, Mice, Inbred C57BL, Spleen cytology, Burns immunology, Ethanol administration & dosage, Immunity, Cellular
- Abstract
Acute ethanol exposure prior to burn injury increases the immune dysfunction seen with burn alone, which has been partially attributed to increased circulating and splenic macrophage production of interleukin-6 (IL-6). The current studies examined the effect dose and timing of ethanol exposure prior to burn on cellular immunity. Mice with high (300 mg/dl) circulating levels of ethanol at the time of burn demonstrated further suppression of the delayed type hypersensitivity (DTH) and splenocyte proliferative responses in comparison to mice with moderate (100 mg/dl) ethanol levels. Interestingly, the increase in macrophage IL-6 secretion seen at the moderate dose was not augmented at the high dose; however, the circulating IL-6 levels did reveal a further increase at the high ethanol dose. There were no alterations in splenocyte subset populations and/or apoptosis at the moderate vs. the high ethanol dose. Moderate ethanol exposure 24 h, in comparison to 30 min, before injury resulted in similar decreases in the DTH. These results suggest that the dose-dependent effects of ethanol on immunity following burn injury are not the result of splenic macrophage IL-6 production as shown at the moderate dose and that the immune suppressive effects of ethanol in this model persist after it is cleared from the circulation. more...
- Published
- 2000
- Full Text
- View/download PDF
22. Ethanol exacerbates T cell dysfunction after thermal injury.
- Author
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Choudhry MA, Messingham KA, Namak S, Colantoni A, Fontanilla CV, Duffner LA, Sayeed MM, and Kovacs EJ
- Subjects
- Alcohol Drinking immunology, Alcohol Drinking metabolism, Animals, Apoptosis drug effects, Apoptosis physiology, Burns immunology, Immunity, Cellular drug effects, Male, Mice, Mice, Inbred C57BL, Spleen cytology, Spleen metabolism, T-Lymphocytes metabolism, Burns metabolism, Central Nervous System Depressants pharmacology, Ethanol pharmacology, Interleukin-2 metabolism, Spleen drug effects, T-Lymphocytes drug effects
- Abstract
To understand the mechanism of suppressed immunity following alcohol consumption and thermal injury, we analyzed T cell functions in a mouse model of acute alcohol exposure and burn injury. Mice with blood alcohol levels at approximately 100 mg/dl were given a 15% scald or sham injury. Mice were sacrificed 48 h after injury. Our data demonstrated a 20-25% decrease in Con A-mediated splenic T cell proliferation (p<0.01) and 45-50% decrease in interleukin-2 (IL-2) production (p<0.01) following burn injury compared to the T cells from sham animals. A further decrease in the proliferation (25-30%) and IL-2 production (40-45%) was detected in T cells derived from burned animals receiving alcohol as compared to burn alone. No significant change in the proliferation and IL-2 production was observed in splenic T cells derived from sham-injured mice regardless of alcohol exposure. Additionally, there was no demonstrable difference in splenocyte apoptosis in any treatment group. These results suggest that alcohol consumption prior to burn injury causes a greater decrease in T cell proliferation and IL-2 production compared to either burn or alcohol injury alone that may further attenuate the cell-mediated immunity and thus enhance susceptibility to infection. more...
- Published
- 2000
- Full Text
- View/download PDF
23. Gender difference in cell-mediated immunity after thermal injury is mediated, in part, by elevated levels of interleukin-6.
- Author
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Gregory MS, Faunce DE, Duffner LA, and Kovacs EJ
- Subjects
- Animals, Antibodies immunology, Antibodies pharmacology, Cell Division drug effects, Concanavalin A immunology, Female, Hypersensitivity, Delayed immunology, Immunity, Cellular drug effects, Immunity, Cellular immunology, Interleukin-6 biosynthesis, Lymphocyte Activation drug effects, Lymphocyte Activation immunology, Macrophages cytology, Macrophages drug effects, Macrophages immunology, Macrophages metabolism, Male, Mice, Mice, Inbred BALB C, Spleen cytology, Spleen drug effects, Spleen immunology, Temperature, Time Factors, Burns immunology, Interleukin-6 immunology, Sex Characteristics
- Abstract
The gender difference in normal immune function has been well documented, however, there is only limited information regarding whether such a difference occurs after injury. To investigate this, we examined cell-mediated immune responses in male and female mice given a 15% total body surface area dorsal scald or sham injury. Both delayed-type hypersensitivity (DTH) and splenocyte proliferative responses were significantly suppressed in males at 1 day and in females at 7 and 10 days post burn (P < 0.01). The decreased splenocyte proliferation was found to be macrophage-dependent and suppression of both immune parameters corresponded with elevated interleukin-6 (IL-6) levels. Furthermore, post-burn treatment with an anti-IL-6 antibody partially restored the DTH response in males at 1 day and females at 10 days post injury and completely restored splenocyte proliferation. These data demonstrate a possible mechanism for the gender difference in cell-mediated immune responses after thermal injury. more...
- Published
- 2000
24. Neutrophil chemokine production in the skin following scald injury.
- Author
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Faunce DE, Llanas JN, Patel PJ, Gregory MS, Duffner LA, and Kovacs EJ
- Subjects
- Animals, Burns pathology, Chemokine CXCL1, Chemokines, CXC, Cytokines analysis, Inflammation Mediators analysis, Interleukin-8 analysis, Male, Mice, Neutrophils pathology, Peroxidase analysis, Skin pathology, Burns immunology, Chemokines metabolism, Neutrophils metabolism, Skin immunology
- Abstract
The present study was conducted to determine whether local production of neutrophil chemoattractant cytokines preceded the influx of neutrophils following dermal scald injury. To accomplish this, dermal tissue was examined for inflammatory infiltrate and the level of KC, a murine homolog of human interleukin-8, at various time points after scald injury. The studies reveal that there was a largely neutrophilic infiltrate at 1 day post-injury which persisted for 4 days. Dermal KC levels increased significantly at 4 h, returned to baseline at 8 h and were elevated again from 1 to 3 days post-burn (P < 0.01). At 3 days post-burn, KC was elevated 15-fold above the level in sham treated mice (P < 0.01). These observations demonstrate that the influx of neutrophils into the skin follows the expression of KC in the skin. This suggests that it should be possible to alter neutrophil accumulation at the wound site by manipulating the local chemokine signal. more...
- Published
- 1999
- Full Text
- View/download PDF
25. Elevation in pulmonary neutrophils and prolonged production of pulmonary macrophage inflammatory protein-2 after burn injury with prior alcohol exposure.
- Author
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Patel PJ, Faunce DE, Gregory MS, Duffner LA, and Kovacs EJ
- Subjects
- Animals, Chemokine CXCL2, Lung anatomy & histology, Male, Mice, Monokines analysis, Time Factors, Alcohol Drinking adverse effects, Burns metabolism, Lung metabolism, Monokines biosynthesis, Neutrophils metabolism, Shock, Traumatic metabolism
- Abstract
Various studies have shown that alcohol exposure before thermal injury leads to increased morbidity and mortality. Pulmonary failure is a major complication seen in these patients. This study examines the effects of prior alcohol exposure on lung pathology after burn injury. There is a marked increase in neutrophil recruitment in the lung after thermal injury, and herein we show that this appears to be significantly elevated in animals given alcohol before burn injury. Consequently, we chose to determine whether there is a difference in pulmonary production of macrophage inflammatory protein (MIP)-2, a potent neutrophil chemoattractant, in mice subjected to a 15% total body surface area scald (or sham) injury with or without prior ethanol treatment. Lung tissue was obtained at various time points after injury and homogenates were assayed for MIP-2 by enzyme-linked immunosorbent assay. At 2 h after injury, peak levels of the chemokine were produced in both burn and burn + alcohol-treated mice. This represents a 7-fold increase above baseline. In mice exposed to burn injury alone, the level of MIP-2 returned to baseline within 8 h. In contrast, mice given alcohol before burn injury continued to show elevated levels of the chemokine at 8 h, after which MIP-2 decreased. This study may provide a basis for understanding the mechanism responsible for the increased neutrophil presence in the lung after thermal injury in individuals who have consumed alcohol. Subsequently, this may lead to the enhanced neutrophil-mediated pulmonary damage observed in these patients. more...
- Published
- 1999
- Full Text
- View/download PDF
26. Bilateral fascia lata patch grafts in a patient with progressive scleromalacia perforans.
- Author
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Kachmaryk M, Bouchard CS, and Duffner LA
- Subjects
- Aged, Humans, Immunosuppressive Agents therapeutic use, Male, Necrosis, Postoperative Complications prevention & control, Scleritis pathology, Transplantation, Autologous, Fascia Lata transplantation, Scleritis surgery
- Abstract
This study was performed to evaluate the use of autogenous fascia lata patch grafts with systemic immunosuppression in the treatment of progressive bilateral scleromalacia perforans. Autogenous fascia lata was compared with donor bank sclera and was demonstrated to be more suitable for this condition. more...
- Published
- 1996
27. The effect of postnatal growth retardation on abnormal neovascularization in the oxygen exposed neonatal rat.
- Author
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Holmes JM and Duffner LA
- Subjects
- Animals, Animals, Newborn, Body Weight, Humans, Infant, Newborn, Litter Size, Oxygen administration & dosage, Rats, Rats, Sprague-Dawley, Retinal Neovascularization pathology, Growth Disorders complications, Retinal Neovascularization etiology, Retinopathy of Prematurity etiology
- Abstract
Severe retinopathy of prematurity (ROP) occurs in the smallest and sickest of premature infants. We hypothesized that, in a rat model of oxygen induced retinopathy, abnormal neovascularization would occur more frequently in larger litters where the pups are subject to postnatal growth retardation. Four litters of newborn Sprague-Dawley rats were studied; rats were randomly mixed to form two large litters (n = 25 each) and two small litters (n = 10 each). All litters were exposed to 7 days cyclic hyperoxia and hypoxia followed by 5 days in room air. ADPase stained retinae were evaluated in a masked manner for the presence and severity of abnormal neovascularization. Fluorescein perfused retinae were digitized and the ratios of vascularized:total retinal area were calculated using computer assisted image analysis. As expected, final weight in the large litters was less than in the small litters (15.3 +/- 3.8g vs. 23.4 +/- 2.1g, p < 0.001). Neovascularization occurred in 53% of rats in the large litters vs. 15% in the small litters (p = 0.009). Rats with retinae demonstrating neovascularization were smaller than those without (16.2 +/- 4.7g vs. 19.6 +/- 5.0g, p = 0.016). The severity of neovascularization in clock h was inversely correlated with final weight (rs = -0.35, p = 0.01) and ratio of vascularized:total retina area (rs = -0.46, p < 0.001). Smaller rat pups raised in larger litters, with resultant growth retardation, develop more frequent and more severe abnormal retinal neovascularization. Our results correlate with clinical experience in the premature infant. more...
- Published
- 1996
- Full Text
- View/download PDF
28. The effect of litter size on normal retinal vascular development in the neonatal rat.
- Author
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Holmes JM and Duffner LA
- Subjects
- Animals, Birth Weight physiology, Female, Fluorescein-5-isothiocyanate, Fluorescent Dyes, Perfusion, Pregnancy, Rats, Animals, Newborn growth & development, Litter Size physiology, Rats, Sprague-Dawley growth & development, Retinal Vessels growth & development
- Abstract
Many animal models of retinal disease use the neonatal rat. Raising rat pups in large litters has been shown to result in postnatal growth retardation. We investigated the effect of litter size on the normal postnatal vascularization of the neonatal rat retina. Sixty-six newborn rat pups were divided among 5 nursing mothers into 3 small litters (n = 10) and 2 large litters (n = 18). On day 6 of life the rats were sacrificed and total retinal and vascularized retinal areas analyzed. The total retinal area was reduced in the rats raised in larger litters (28.6 mm2 vs. 25.9 mm2 p < 0.001) but there was a more pronounced reduction in vascularized retinal area (67% vascularized vs. 54% vascularized, p < 0.001). Postnatal vascularization of the normal rat retina may be influenced by litter size. more...
- Published
- 1995
- Full Text
- View/download PDF
29. The effect of raised inspired carbon dioxide on developing rat retinal vasculature exposed to elevated oxygen.
- Author
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Holmes JM, Duffner LA, and Kappil JC
- Subjects
- Animals, Animals, Newborn, Carbon Dioxide administration & dosage, Female, Fluorescein Angiography, Fundus Oculi, Humans, Image Processing, Computer-Assisted, Infant, Newborn, Male, Oxygen administration & dosage, Rats, Rats, Sprague-Dawley, Retinal Vessels physiopathology, Retinopathy of Prematurity pathology, Hypercapnia physiopathology, Hyperoxia physiopathology, Retinal Vessels pathology, Retinopathy of Prematurity physiopathology
- Abstract
Hyperoxia is a risk factor for retinopathy of prematurity (ROP), a blinding disease in infants. However, ROP develops in human infants without raised arterial oxygen levels, such as in cyanotic congenital heart disease. In these infants raised pCO2 may be a risk factor. We investigated the effect of inspired CO2 on oxygen induced retinopathy in the rat. 56 newborn Sprague-Dawley rats were exposed to high cyclical O2 for seven days. In a control group, 27 rats were exposed to negligible CO2 by the use of soda lime. In the high CO2 group, 29 rats were exposed to elevated CO2 by omitting soda lime from their chambers. Rats in both groups had a recovery period of three days in room air following cyclical O2 exposure. On the eleventh day all rats were sacrificed after intracardiac injections of fluorescein under deep anesthesia and the retinae were dissected and flat mounted for fluorescent microscopy. The ratio of vascularized:total retinal area was calculated using computer assisted image analysis. In the high CO2 group 62% +/- 7% SD of the retina was vascularized vs. 81% +/- 7% in low CO2 group (p < 0.001). Elevated inspired CO2 results in pronounced retardation of retinal vascular development in neonatal rats exposed to fluctuating raised oxygen. more...
- Published
- 1994
- Full Text
- View/download PDF
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