Mast cells and resistance to peritoneal sepsis after burn injury

A mouse model of burn injury demonstrates increasing mortality to an infectious challenge in the form of cecal ligation and puncture (CLP) reaching a peak at 10 days after injury. Because it is widely believed that peritoneal mast cells play an important role in the defense against peritoneal sepsis, we wished to explore the possibility that peritoneal mast cell dysfunction contributed to increased CLP mortality after burn injury. Kit(W-v) C57BL/6 mice, which were shown to lack peritoneal mast cells by cytospin and flow cytometry, and normal littermate control animals were subjected to 25% burn or sham burn injury and 10 days later underwent CLP. Burn injured Kit(W-v) and normal littermates had a high CLP mortality when compared with sham-injured Kit(W-v) and normal littermates (P < 0.003), but the sham- and burn-injured Kit(W-v) and normal littermate animals did not differ from one another with respect to CLP mortality. This result prompted a comparison of CLP mortality in untreated WBB6F1 Kit(W/W-v) mice, known to be mast cell deficient, and normal littermate controls, as well as untreated C57BL/6 Kit(W-v) and normal littermates. The WBB6F1 Kit(W/W-v) mice showed significantly increased mortality after CLP as compared with the littermate controls (P = 0.03), whereas both C57BL/6 Kit(W-v) and littermate controls had very low mortality after CLP. A study of peritoneal cell populations 24 h after CLP failed to reveal an obvious cause for the difference in CLP survival between the two mast cell-deficient strains. Tumor necrosis factor-alpha (TNF-alpha) measurements in peritoneal fluid showed appreciable amounts of TNF-alpha in the littermate controls of both strains and little in the fluid obtained from the mast cell-deficient animals of both strains. We conclude that peritoneal mast cell dysfunction is unlikely to be a major cause of decreased resistance to peritoneal sepsis in burn-injured animals and that the importance of peritoneal mast cells in combating peritoneal sepsis in the mouse appears to be strain dependent.     

Early coagulation disorders after severe burn injury: impact on mortality

Objective To evaluate the time course of coagulation markers in the early postburn period and clarify the role of coagulation alterations in organ failure and in mortality prognosis. Design and setting This prospective study was conducted in the burn ICU of a tertiary hospital. Patients 45 patients with severe thermal burn injury. Measurements and results Clinical data and coagulation and fibrinolysis parameters were measured during the first postburn week. The ICU 28-day mortality rate was 33%. Significant differences in the time course of coagulation markers were observed between survivors and nonsurvivors. SOFA score distinguished between patients with overt and nonovert disseminated intravascular coagulation (DIC) during the overall investigation period. Presence of overt DIC was related to mortality (OR = 0.1). Antithrombin, protein S, plasminogen activator inhibitor 1, and SOFA score on day 3, protein C on day 5, and thrombin/antithrombin complexes on day 7 revealed a good prognostic value for ICU mortality, according to the area under ROC curves. Conclusions Severe thermal injury is associated with the early activation of coagulation cascade, presence of DIC, organ failure, and increased mortality.     

Impact of oxandrolone treatment on acute outcomes after severe burn injury

Pharmacologic modulation of hypermetabolism clearly benefits children with major burns, however, its role in adult burns remains to be defined. Oxandrolone appears to be a promising anabolic agent although few outcome data are as yet available. We examined whether early oxandrolone treatment in severely burned adults was associated with improved outcomes during acute hospitalization. We evaluated for potential associations between oxandrolone treatment and outcomes in a large cohort of severely burned adults in the context of a multicenter observational study. Patients were dichotomized with respect to oxandrolone treatment, defined as administration within 7 days after admission, with duration of at least 7 days. Acute hospitalization outcomes were compared with univariate and multivariate analyses. One hundred seventeen patients were included in this analysis. Mean patient age was 42.6 years (range, 18-86); 77% were male, with an average TBSA of 44.1%. Baseline and injury characteristics were similar among treatment and nontreatment cohorts. Oxandrolone treatment (N = 59) did not impact length of stay but was associated with a lower mortality rate (P = .01) by univariate analysis. Oxandrolone treatment was independently associated with higher survival by adjusted analyses (P = .02). Examination of early oxandrolone treatment in this cohort of severely burned adults suggests that this therapy is safe and may be associated with improved survival. Further studies are necessary to define the exact mechanisms by which oxandrolone is beneficial during inpatient treatment.     

Neuropathy after burn injury

The purpose of this study was to evaluate the incidence of neuropathy in a consecutive cohort of patients with major burn injuries and investigate the clinical correlates for both mononeuropathy and generalized peripheral polyneuropathy. Of 572 patients examined, 64 (11%) patients had clinical evidence of mononeuropathy or peripheral neuropathy or both. Associations of mononeuropathy and peripheral neuropathy with potential risk factors were identified using logistic regression analyses. Electrical cause (odds ratio [OR] = 4.1022, P < .01), history of alcohol abuse (OR = 2.2893, P <.05), and number of days in intensive care (OR = 1.0457, P < .001) were significantly associated with mononeuropathy. The number of days in intensive care (OR = 1.0740, P < .001) and patient age (OR = 1.0543, P < .01) were significantly associated with peripheral neuropathy. This study demonstrates that neuropathy is a common complication of severe burn injury in patients who are older, critically ill, have an electrical cause, or history of alcohol abuse.     

Sensibility after burn injury

Summary. Thresholds for touch, temperature, pain and two-point discrimination were examined in 27 healthy subjects and in 36 burn patients. Three groups of injuries were examined; superficial dermal burns, which were allowed to heal spontaneously, deep dermal and subdermal burns treated by either early or late excision and skin grafting. Uninjured areas on the contralateral side served as control. In spontaneously healed superficial burns, the sensibility recovered to normal, except for touch. In deep dermal or subdermal burns all thresholds were significantly higher than in the corresponding control areas. There was no recovery beyond one month after the injury. The sensibility was better on the upper than on the lower extremities and also in deep dermal than in subdermal burns. There was no significant difference in sensibility between burns excised and grafted early or late, respectively. The results indicate that current treatment of deep dermal and subdermal burns is not followed by complete recovery of cutaneous sensation. Furthermore, even superficial burns results in incomplete recovery of touch sensibility.     

Characterization of the inflammatory response during acute and post-acute phases after severe burn

Severe burn causes a pronounced hypermetabolic response characterized by catabolism and extensive protein wasting. We recently found that this hypermetabolic state is driven by a severe inflammatory response. We characterized in detail the kinetics of serum levels of a panel of cytokines in a rat model, which may serve as reference for the development of therapeutic interventions applicable to humans. Male Sprague-Dawley rats (n = 8) received a full-thickness burn of 60% total body surface area. Serum was harvested 1, 3, 6, 12, 24, 48, 96, and 168 h after burn. Eight serum cytokines commonly used to assess the inflammatory response in humans, such as IL-1beta, IL-6, IL-10, TNF, vascular endothelial growth factor, and monocyte chemotactic protein 1, and the rat-specific cytokines cytokine-induced neutrophil chemoattractant (CINC) 1, CINC-2, and CINC-3 were measured by enzyme-linked immunosorbent assay technique and were compared with controls (n = 4). Statistical analysis was conducted using the t test, with P < 0.05 considered as significantly different. Thermal injury resulted in significantly increased serum levels of IL-1beta, IL-6, IL-10, monocyte chemotactic protein 1, CINC-1, CINC-2, and CINC-3 when compared with the concentrations detected in nonburned rats (P < 0.05). Serum levels of TNF-alpha and vascular endothelial growth factor in burned rats were not found to be significantly different to controls. Burn causes a profound inflammatory response in rats. Specific cytokines known to increase in humans postburn such as IL-1 beta, IL-6, IL-10, MCP-1, and IL-8 (CINC-1, CINC-2, and CINC-3 in the rat) were also observed in our rat burn model, which now allows us to study new anti-inflammatory treatment options.     

Urine proteins after burn injury

Two-dimensional immunoelectrophoresis was used to examine the proteins present in urine during the first week following burn injury. Of the "serum" proteins present in the urine some glycoproteins were found to be in different relative proportions from those observed in serum. In patients sustaining severe burns the amount of protein excreted was increased compared to patients with mild burns and to controls. alpha 1-Antichymotrypsin detected in the urine of patients with severe burns was at times seen as a twin peak. This altered peak was of slower electrophoretic mobility and may represent a polymer of the protein or a complex of the protein with some other, possibly tissue-derived, protein.     

Innate immunity SNPs are associated with risk for severe sepsis after burn injury

OBJECTIVE: To analyze allelic association with clinical outcome in a cohort of burn patients. PATIENTS: Two hundred twenty-eight individuals with burns > or =15% total body surface area without significant non-burn related trauma who survived >48 hours post-admission were enrolled. One hundred fifty-nine of these patients were analyzed previously. METHODS: Candidate polymorphisms within interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), cellular differentiation marker 14 (CD14) and toll-like receptor 4 (TLR4) were evaluated by logistic regression analysis for association with increased risk for severe sepsis (sepsis plus organ dysfunction or shock). RESULTS: After adjustment for age, burn size, ethnicity, gender and inhalation injury, alleles at TNF-alpha (308G, p=0.013), TLR4 (+896G, p=0.027), IL-6 (174C, p=0.040) and CD14 (159C, p=0.047) were significantly associated with an increased risk for severe sepsis. CONCLUSIONS: Carriage of variant alleles at immune response genes were associated with increased risk for severe sepsis after burn injury.     

烧伤早期心肌组织几种炎症相关基因表达变化的实验研究

目的 :观察烧伤后心肌组织几种炎症相关基因表达变化 ,探讨其与心肌损害的关系。方法 :采用大鼠4 0 %体表面积 度烫伤模型 ,于伤后 0 h(正常组 )、1h、3h、6 h、12 h、2 4 h用逆转录聚合酶链反应 (RT PCR)方法检测心肌组织肿瘤坏死因子 α(TNFα)、白介素 1β(IL 1β)、诱导型一氧化氮合酶 (i NOS)及胞浆型磷脂酶 A2 (c PL A2 ) m RNA水平 ,四道生理记录仪监测左室收缩压 (L VSP)、左室舒张末压 (L VEDP)和左室压力最大上升 /下降速率 (± dp/dtmax)变化。结果 :烫伤后 1h TNFα和 c PL A2 m RNA表达显著上调 (P均 <0 .0 1) ,此后一直维持高表达状态 ;IL 1β m RNA于伤后 3h表达明显升高 (P<0 .0 1) ,伤后 12 h降至正常水平 ;i NOS m RNA水平除伤后 1h稍上调外 ,其余时间点反而下降。左室收缩功能 (L VSP、+dp/dtmax)和舒张功能 (L VEDP、 dp/dtmax)于伤后 3h显著下降 (P均 <0 .0 1) ,12 h达谷底。左心功能变化与 TNFα、c PL A2表达呈负相关 (P均 <0 .0 5 )。结论 :炎症相关基因 TNFα、c PL A2 及 IL 1β参与了烧伤后心肌局部失控性炎症反应 ,其上调表达可能是烧伤后心肌损害的重要原因之一。     

严重烧伤后小鼠腹腔巨噬细胞肿瘤坏死因子的变化及免疫功能机制

背景严重烫伤导致机体免疫系统各方面的功能紊乱,活化的巨噬细胞可分泌许多生物活性递质.烧伤后巨噬细胞功能紊乱与信号转导的关系目前尚不清楚.目的观察严重烫伤后不同时相点及运用特异性NF-κB抑制剂吡咯啉烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)后小鼠腹腔巨噬细胞内NF-κB活性、IκB-α的表达及肿瘤坏死因子(TNF-α)的变化,从信号转导的角度探讨巨噬细胞功能紊乱的机制.设计随机对照的实验研究.单位创伤、烧伤与复合伤国家重点实验室.材料实验于1999-01/06在第三军医大学烧伤研究所实验室(国家级)完成.实验动物为健康清洁级近交系昆明小白鼠30只.干预以小鼠常规烫伤模型造成体表面积15%Ⅲ度烫伤.实验按烫伤前及伤后不同时相随机分为6组,即0(正常对照组),2,6,12,24,48 h组.收集腹腔巨噬细胞.采用放射免疫法检测TNF-α的含量,电泳迁移率改变分析法测NF-κB的活性,免疫印迹法测IκB-α的表达,反转录-PCR测TNF-α mRNA的表达.主要观察指标①检测TNF-α的含量.②测定NF-κB的活性.③检测IκB-α的表达.④测TNF-α mRNA的表达.结果烫伤后巨噬细胞分泌TNF-α亢进,于伤后12 h达到高峰,为(1 085.65±122.99)ng/L,较正常对照组明显增高(t=14.92,P＜0.01).NF-κB活性于伤后明显活化,于2 h达到了高峰(t=13.31,P＜0.01),为(56.8±7.3)RDU,早于TNF-α的增多.与正常对照组相比,IκB-α的表达于烫伤后2 h显著下降(t=4.23,P＜0.01),达到0.632±0.086,以后上升,至24 h达到高峰(t=7.06,P＜0.01),为1.161±0.097,48 h稍降(t=4.82,P＜0.01),为1.149±0.167.以伤后12 h为调控点,予PDTC后NF-κB活性及TNF-α mRNA表达量均显著下降(P＜0.01).结论烫伤后NF-κB活性及TNF-α表达明显增强,IκB-α对NF-κB在高水平上维持着一种制约关系.烫伤后小鼠腹腔巨噬细胞内NF-κB信号途径参与TNF-α表达的调控.     

Hypoxia-hypotension decreases pressor responsiveness to exogenous catecholamines after severe traumatic brain injury in rats

OBJECTIVE: To quantify the phenylephrine pressor responsiveness after severe brain injury combined with hypoxia-hypotension, and to study the respective roles of brain injury and hypoxia-hypotension in the observed alteration. DESIGN: Randomized study. SETTING: Accredited animal laboratory. SUBJECTS: Adult Sprague Dawley rats. INTERVENTIONS: Anesthetized animals were assigned to control, brain injury, hypoxia-hypotension, and brain injury combined with hypoxia-hypotension groups. Brain injury was induced with an impact-acceleration device. During the 15-min hypoxia-hypotension, arterial oxygen pressure was decreased to 40 torr (5.3 kPa) and mean arterial pressure to 30 mm Hg. Thirty-six of the 53 included rats were alive at the end of hypoxia-hypotension (nine animals per group). In an additional group (Hypo, n = 8), mean arterial pressure was lowered to the level observed in brain injury combined with hypoxia-hypotension with pentobarbital infusion. Sixty minutes after injuries (T60), animals received 0.1, 1, and 10 microg/kg phenylephrine in a random order. Pressor responsiveness to phenylephrine was defined as maximal postinjection minus preinjection mean arterial pressure. MEASUREMENTS AND MAIN RESULTS: During hypoxia-hypotension, mortality was higher and residual restored blood volume was lower (p <.01) in the animals with brain injury and hypoxia-hypotension compared with hypoxia-hypotension alone. At T60, mean arterial pressure (mm Hg) was lower (p <.01) in the brain injury group (83 +/- 22) compared with controls (110 +/- 10) and in brain injury combined with hypoxia-hypotension (76 +/- 18) compared with controls and hypoxia-hypotension (107 +/- 14). Pressor responsiveness (mm Hg) to 1 and 10 microg/kg phenylephrine was less (p <.05) in brain injury combined with hypoxia-hypotension (15 +/- 6 and 44 +/- 8) and hypoxia-hypotension (15 +/- 3 and 44 +/- 8) compared with controls (26 +/- 2 and 57 +/- 11). No significant difference was observed for phenylephrine pressor responsiveness between controls and the Hypo group (25 +/- 5 and 66 +/- 7). CONCLUSIONS: Combination of brain injury and hypoxia-hypotension induces a severe hemodynamic alteration associated with a decreased pressor responsiveness to phenylephrine. Transient hypoxia-hypotension is responsible for the depressed alpha-1 adrenergic reactivity.     

Vagal nerve stimulation in treatment of intractable partial seizures: nursing implications.

Seizures are the result of abnormal synchronization of electrical activity in the brain. Medical therapy is unsuccessful in controlling seizures for many patients with partial seizures and surgery may not be a viable option. An alternate mode of treatment of intractable partial seizures is needed. Vagal nerve stimulation is a treatment modality under investigation. Stimulating the vagus nerve is hypothesized to desynchronize cerebral electrical activity, yielding an antiepileptic effect. A multicenter vagal nerve stimulation study is currently underway.     

Familial values as factors influencing long-term psychological adjustment of children after severe burn injury

This study replicates earlier findings that children who survive severe burn injury do make positive psychological adjustment. Family support and a family value of autonomy were predicted to be critical variables in promotion of psychological adjustment. In addition, the study presents the hypothesis that length of time after burn injury and level of intelligence are contributing factors in psychological adjustment. Forty-four adolescents with a mean of 60% total body surface area (TBSA) full-thickness burns were studied. Half of the subjects scored within the normal range on a measure of psychological adjustment. Familial value patterns were critical in the prediction of psychological adjustment. Positive psychological adjustment was predicted by greater family cohesion, independence, and more open expressiveness within the family. Level of intelligence did not contribute to adjustment. Length of time after injury, if it is important to psychological healing, appears to be a factor only during the initial 2 years after burn injury.     

Community integration outcome after burn injury

It is important to focus on community integration, including return to work and school, early during treatment after burn injuries. A careful analysis of the potential barriers to return to activities can help focus a treatment team and provide appropriate support for a return to work or school plan. Psychological intervention is often an important component of a return to work or school plan. Vocational rehabilitation counselors and school reentry coordinators are valuable assets to coordinating with a treatment team and communicating with a workplace or school. A successful return to work or school is often achieved with a coordinated and supportive approach.     

Respiratory changes after major burn injury

In 32 major burn patients, routine respiratory measurements and blood gases analysis were performed. Striking differences were found between survivors and nonsurvivors in these variables. Marked increased in minute volume and respiratory rate were observed in nonsurvivors starting from the 6th day postburn, while PaCO2 increased with larger tidal and minute volumes. At the same time, PaO2 was lower than in survivors. In survivors, the closing volume, maximum mid-expiratory flow rate, and peak rate were lower than the predicted normal values. This may indicate that after major burn injury, ventilatory power decreased and some pathological changes occurred in small airways and alveoli without apparent pulmonary complications. Marked differences in the changes of respiratory rate and min volume between survivors and nonsurvivors may indicate the value of simple respiratory measurements for prediction of outcome in burn patients.     

Restoring nitrogen balance after burn injury

The metabolic response to burn injury is characterized by weight loss and marked protein wasting. This phenomenon is mediated hormonally, resulting in hypermetabolism. Energy expenditure increases linearly with the extent of burn injury, reaching a plateau of twice resting energy expenditure when 50% of the total body surface area is involved. It is therefore essential to minimize other factors that may further augment postburn catabolism. Occlusive dressings, a warm ambient environment, analgesics, and timely closure of the burn wound are all important therapeutic measures in this regard. Furthermore, it is imperative to institute early nutritional support in order to offset the negative metabolic effects of severe burn injury.     

Sleep disturbance after burn injury.

This study describes sleep disturbance and related factors in a group of 74 patients at 1 week after discharge using a sleep problems questionnaire developed by the authors. Results indicated that a significant proportion of patients reported a problem with their sleep (73%). Several items were identified as highly prevalent, including frequent nighttime awakenings (87%), napping during the daytime (65%), sleeping alone (64%), experiencing pain during the night (62%), and difficulties with sleep onset (62%). Results suggest numerous possible interventions to improve patients' sleep quality. The usefulness of a more extensive questionnaire was also indicated.