Early abnormal fibrinolysis and mortality in patients with thermal injury: a prospective cohort study.

INTRODUCTION: Abnormal fibrinolysis early after injury has been associated with increased mortality in trauma patients, but no studies have addressed patients with burn injury. This prospective cohort study aimed to characterize fibrinolytic phenotypes in burn patients and to see if they were associated with mortality. METHODS: Patients presenting to a regional burn centre within 4 h of thermal injury were included. Blood was collected for sequential viscoelastic measurements using thromboelastography (RapidTEG™) over 12 h. The percentage decrease in clot strength 30 min after the time of maximal clot strength (LY30) was used to categorize patients into hypofibrinolytic/fibrinolytic shutdown (SD), physiological (PHYS) and hyperfibrinolytic (HF) phenotypes. Injury characteristics, demographics and outcomes were compared. RESULTS: Of 115 included patients, just over two thirds were male. Overall median age was 40 (i.q.r. 28-57) years and median total body surface area (TBSA) burn was 13 (i.q.r. 6-30) per cent. Some 42 (36.5 per cent) patients had severe burns affecting over 20 per cent TBSA. Overall mortality was 18.3 per cent. At admission 60.0 per cent were PHYS, 30.4 per cent were SD and 9.6 per cent HF. HF was associated with increased risk of mortality on admission (odds ratio 12.61 (95 per cent c.i. 1.12 to 142.57); P = 0.041) but not later during the admission when its incidence also decreased. Admission SD was not associated with mortality, but incidence increased and by 4 h and beyond, SD was associated with increased mortality, compared with PHYS (odds ratio 8.27 (95 per cent c.i. 1.16 to 58.95); P = 0.034). DISCUSSION: Early abnormal fibrinolytic function is associated with mortality in burn patients.

Shedding of the endothelial glycocalyx is quantitatively proportional to burn injury severity.

Limited information exists regarding endothelial dysfunction following burn injury. This project aims to evaluate whether thermal injury results in shedding of the endothelial glycocalyx in a manner quantitatively proportional to injury severity, and whether theloss of intact glycocalyx is measurable in end organs. C57BL/6 mice were grouped as uninjured controls, 10% or 25% Total Body Surface Area (TBSA) scald burns. Blood and tissue sampling was performed over a specific time course. Plasma levels of shed syndecan-1, a marker of glycocalyx damage, were quantified by ELISA. Lung and spleen sections were stained with immunofluorescent anti-syndecan-1 antibodies to evaluate intact glycocalyx. Plasma syndecan-1 levels were higher in injured versus uninjured animals. Normalized levels of syndecan-1 in burned mice were significantly increased compared to hour 0 (p<0.05) at hours 4 and 8 post-injury in the 10% TBSA, and at hour 4 in the 25% TBSA group. Levels in the 10% and 25% TBSA groups peaked at hour 4 with fold change of 2.3 and 2.4 respectively. There was less pulmonary syndecan-1 immunostaining in burned animals compared to controls, and the levels inversely correlated with systemic shed syndecan- 1, beginning at hour 4 in the 10% TBSA injury group and at all time points in the 25% TBSA injury group, (0.27±0.06 and 0.14±0.04 respectively for hour 4). Similarly, there was less spleen syndecan-1 immunostaining in burned animals compared to controls at all time points. Burn injury causes shedding of syndecan-1 in a murine model, with levels correlated to injury severity and loss of the glycocalyx in lung and spleen. This work provides further insight into quantification and temporality of glycocalyx damage and systemic response to burn.

Les données concernant la dysfonction endothéliale après brûlure sont parcellaires. Les buts de cette étude étaient d'établir une corrélation entre la perte de glycocalyx et la gravité de la brûlure et si cette perte était mesurable au niveau des organes. Des souris C57BL/6 ont été réparties en groupes contrôle, brûlure 10% et brûlure 25% de SCT. Des prélèvements de sang et de tissus ont été réalisés à intervalles prédéterminés. Les taux plasmatiques de syndecan 1 (S1), marqueur de lésion du glycocalyx, ont été mesuré par méthode ELISA. Des échantillons de poumon et de rate ont été mis en présence d'anticorps anti S1, afin d'évaluer le glycocalyx intact. Les taux plasmatiques de S1 étaient plus élevés que ceux du groupe contrôle. Chez les souris brûlées sur 10% de SCT, les taux de S1 à 4h et 8 h étaient supérieurs au taux avant brûlure, ceci n'étant observé qu'à h4 chez les souris brûlées sur 25% de SCT. Le pic de S1 se produisait à h4, avec un rapport de x2,3 (10%) et x2,4 (25%) par rapport à la valeur de base. A partir de h4, on observait une baisse de complexes S1-antiS1 dans les poumons des souris brûlées sur 10% (0,27 +/- 0,06), inversement corrélée aux taux plasmatiques de S1. Cette observation se répétait lors de tous les dosages chez les 25% (0,14 +/- 0,04 à h4). Les mêmes constatations étaient faites sur les échantillons de rate. La brûlure cause des lésions du glycocalyx, parallèles à sa gravité. Ces travaux ouvrent le champ à des recherches futures sur les lésions du glycocalyx et la réponse inflammatoire aux brûlures.

Hydroconductive and silver-impregnated foam dressings: a comparison.

OBJECTIVE: As the number of commercially available wound dressings is increasing rapidly, it is important for clinicians to understand the strengths and limitations of each and to recognise relationships between wound type and dressing properties to obtain optimal healing results. Our aim is to test the antimicrobial activity of two dressings. METHOD: A hydroconductive (HC) dressing and a silver-impregnated foam (SIF) dressing were compared for their potential to reduce the levels meticillin-resistant Staphylococcus aureus (MRSA). We also assessed MRSA-derived biologically active components in liquid or agar matrices, simplified models for heavily exuding or dry wounds respectively, and in an in vivo animal model with MRSA infected wounds. RESULTS: In the agar model (dry wounds) both dressings showed a strong reduction in MRSA activities within 24 hours post-application. The antibacterial effects of the SIF dressing were more pronounced in the liquid model, however, at an increasing cytotoxic cost. In agreement with these in vitro results, assessment of dressings using an MRSA-infected wound in an rat model showed a decrease in MRSA which was significant 7 days post-burn and inoculation, with more compromised viability of MRSA. Dressings showed a similar capability to reduced and eliminate toxic shock syndrome toxin (TSST-1) at day 7 post-burn in the animal model but not at day 4, where the SIF dressing was more potent Conclusion: These results confirm the advantages of using silver in reducing bacterial load in wound treatment, except for conditions of highly exuding wounds where the cytotoxic properties of silver may offset these advantages and HC dressing use is more suitable.

A Translational Animal Model for Scar Compression Therapy Using an Automated Pressure Delivery System.

BACKGROUND: Pressure therapy has been used to prevent and treat hypertrophic scars following cutaneous injury despite the limited understanding of its mechanism of action and lack of established animal model to optimize its usage. OBJECTIVES: The aim of this work was to test and characterize a novel automated pressure delivery system designed to deliver steady and controllable pressure in a red Duroc swine hypertrophic scar model. METHODS: Excisional wounds were created by dermatome on 6 red Duroc pigs and allowed to scar while assessed weekly via gross visual inspection, laser Doppler imaging, and biopsy. A portable novel automated pressure delivery system was mounted on developing scars (n = 6) for 2 weeks. RESULTS: The device maintained a pressure range of 30 ± 4 mm Hg for more than 90% of the 2-week treatment period. Pressure readings outside this designated range were attributed to normal animal behavior and responses to healing progression. Gross scar examination by the Vancouver Scar Scale showed significant and sustained (>4 weeks) improvement in pressure-treated scars (P < .05). Histological examination of pressure-treated scars showed a significant decrease in dermal thickness compared with other groups (P < .05). Pressure-treated scars also showed increased perfusion by laser Doppler imaging during the treatment period compared with sham-treated and untreated scars (P < .05). Cellular quantification showed differential changes among treatment groups. CONCLUSION: These results illustrate the applications of this technology in hypertrophic scar Duroc swine model and the evaluation and optimization of pressure therapy in wound-healing and hypertrophic scar management.

The indications and outcome of paediatric corneal transplantation in New Zealand: 1991-2003.

AIM: To evaluate patient characteristics, indications, surgical details, and outcome of paediatric keratoplasty in New Zealand. METHODS: As part of a prospective longitudinal study, paediatric keratoplasty data collected by the New Zealand National Eye Bank (NZNEB) was analysed for the 13 year period 1991-2003. RESULTS: During the study period the NZNEB supplied 2547 corneas for keratoplasty, of which 65 (3%) were used for paediatric patients (14 years or younger). The 65 keratoplasties were performed in 58 eyes of 52 patients (66% male, 34% female, mean age 10.6 years, SD 4.3 years). Indications were classified into three groups: congenital (16%, n = 9), acquired non-traumatic (74%, n = 43), and acquired traumatic (10%, n = 6). Peters' anomaly (7% of total), keratoconus (67%), and penetrating trauma (8%) were the most common indications in each group, respectively. 82% of keratoplasties with known outcome survived (clear graft) 1 year postoperatively, 16% failed, and one patient died. Keratoplasty for congenital indications had a lower 1 year survival rate (78%) compared to acquired non-traumatic (85%) and traumatic (100%) indications, although the difference was not statistically significant (p = 0.65). 38% of patients with known outcome had a 1 year postoperative best corrected Snellen visual acuity (BCSVA) of 6/9 or better, and 60% had a BCSVA of 6/18 or better. Visual outcome was significantly better for acquired compared to congenital indications (p = 0.03). CONCLUSION: Analysis of the NZNEB database provided valuable information in relation to paediatric keratoplasty in New Zealand. In particular, this study highlighted an unusually high prevalence of keratoconus as an indication for keratoplasty. In addition, a high 1 year survival rate and good visual outcome were identified, especially in cases of keratoplasty for acquired conditions.

Metabolic rate and thermal stability during honeybee foraging at different reward rates.

During honeybee foraging, the stabilization of thoracic temperature (Tth) at elevated values is necessary to meet the power requirements of flight at different air temperatures (T(a)). To understand how the bee achieves thermal stability at different reward rates, the metabolic rates of undisturbed foraging bees were measured at different T(a) values and different sucrose solution flow rates. Metabolic heat production, calculated from the rate of carbon dioxide production, decreased linearly from 49.7 to 23.4 mW as T(a) increased from 19 to 29 degrees C (sucrose flow rate 1.75 microl x min(-1), 50 % w/w). In contrast, crop load and inspection rate remained constant. Metabolic rate displayed a linear relationship with both T(a) and the logarithm of the flow rate of sucrose solution (range analyzed 0.44-13.1 microl x min(-1), 50 % w/w). Metabolic rate decreased by 3.13+/-0.52 mW (mean +/- s.e.m., N=37) for every 1 degrees C increase in T(a) and increased by 4.36+/-1.13 mW for a doubling in flow rate. These changes in metabolic power output might be used to achieve thermal stability during foraging. It is suggested that the foraging bee might increase its Tth in accordance with the reward rate.

Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers.

BACKGROUND: Immune function declines with age, increasing risk for infection and delaying wound healing. Arginine enhances immune function and healing of standardized wounds in healthy elderly persons. The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers. METHODS: Residents with one or more pressure ulcers were recruited from two local nursing homes. Subjects were randomized to receive 0 g (n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11; 87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance, ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes. Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function. RESULTS: Supplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinically relevant changes in electrolyte levels among groups. Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes. When data from nursing homes were considered individually, arginine supplementation did not enhance the proliferative response. In subjects from nursing home 2 only, there was a 38% and 75% decrease (p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine, respectively. Interleukin 2 production was no different among supplementation groups. CONCLUSIONS: Pharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons. This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged. Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use.

Changes in the metabolic rate of the foraging honeybee: effect of the carried weight or of the reward rate?

The metabolic rate of free flying honeybees (Apis mellifera ligustica) foraging on a multiple automatic feeder was measured in complete absence of perturbation. Each time the sucrose flow rate was doubled, the metabolic rate increased by 18.2 +/- 2.0% (14.7 microl CO2 min(-1) and final crop load by 25.1 +/- 2.4% (7.04 microl). The possibility that the heavier load carried by the bees caused the increase in the metabolic rate was analyzed in detail. It was found that, for the same weight in the crop, the metabolic rate increased with the increasing reward rate. Therefore, a factor other than the carried weight might account for this increase: a motivational drive, whose intensity may depend on the reward rate at the food source. Although at higher reward rates metabolic rate increased during the visit, at lower reward rates it remained constant, suggesting that the effect of the carried weight on the metabolic rate might be controlled by this motivational drive. The hypothesis that honeybees maximize individual efficiency by reducing their crop load loses support, as foraging costs are not determined by the carried weight. The functional meaning of the reduction in crop load would be to increase the informational exchange at the hive.

Oxygen consumption in the foraging honeybee depends on the reward rate at the food source.

Oxygen consumption of the honeybee Apis mellifera ligustica was measured as a function of the flow rate supply of sucrose solution at an automatic feeder located inside a respirometric chamber. Trained bees freely entered the respirometric chamber and collected the sucrose solution supplied. The mean value of the O2 consumption rate per visit increased with the sucrose flow rate, and for a given flow rate, with increasing locomotor activity. However, when no locomotor activity was displayed, O2 consumption also increased with increasing nectar flow rate. Crop load attained at the end of the visit showed a positive relationship with the nectar flow rate; however, for a given flow rate, O2 consumption showed either no correlation or a negative one with the final crop load attained. It is concluded that the energy expenditure of the foraging bee is controlled by a motivational drive whose intensity depends on the reward rate at the food source.

Development of fetal thymocytes in organ culture: effect of corticosteroids.

Corticosteroids affect the development of fetal foregut-derived organs in which epithelial-mesenchymal interactions are associated with the developmental process. The thymus is one such organ and is profoundly sensitive to corticosteroids when mature. In this study corticosterone (CS) effects on fetal thymocyte development were investigated using a fetal thymus organ culture system which allows the growth, differentiation, and function of developing thymocytes to be monitored in vitro. CS inhibited, but did not block growth of fetal thymocytes, although the appearance of mature thymocytes was inhibited, similar to previously reported effects of interleukin 2 (IL2). CS enhanced the proportion of Mac1+, Ia+ and FcR+ cells and maintained high levels of IL2 receptor (IL2R) positive immature cells. Functional cytotoxic cells were detected in CS-treated organ cultures which expressed a Thy 1-, CD8- phenotype, atypical for thymus derived killer cells. While this cytotoxicity may be stimulated by CS, it could simply be due to a relative depletion of the main pool of thymocytes. These cytotoxic cells may have a role in directing apoptotic mechanisms occurring during thymocyte development.

Development of thymocytes in organ culture: migrant cells with natural killer cell characteristics.

During organ culture of foetal thymic lobes, up to 5% of the thymic cells migrate out of the lobes and a majority of these have phenotypic characteristics of thymocytes or macrophages. Interleukin-2 (IL-2) increases the number of these migrant cells, and cytotoxic cells can be detected which display natural killer cell surface markers. In contrast, although cytotoxic activity can be detected in cells from adult thymic fragments cultured with IL-2, the cytotoxic activity is not detected with natural killer sensitive target cells. The appearance of natural killer-like cells during the culture of foetal thymic lobes suggests that they are involved in differentiation events which occur at this time in the thymus.