Relationship between arterial, mixed venous, and internal jugular carboxyhemoglobin concentrations at low, medium, and high concentrations in a piglet model of carbon monoxide toxicity

OBJECTIVE: This study tested the hypothesis that mixed venous carboxyhemoglobin concentrations (V-COHb) and internal jugular carboxyhemoglobin concentrations (I-COHb) accurately predict arterial carboxyhemoglobin concentrations (A-COHb). In addition, this study tested the hypothesis that there is a high correlation at low (COHb, 0% to 10%), moderate (COHb, >10% to 40%), and high (COHb, >40%) concentrations between V-COHb, I-COHb, and A-COHb. DESIGN: The study was a prospective comparison of A-COHb, V-COHb, and I-COHb concentrations in piglets exposed to increasing concentrations of carbon monoxide over 6 hrs to achieve a concentration of > or =60% COHb. Carboxyhemoglobin measurements were evaluated by analysis of variance and correlation analysis. Agreement between V-COHb and A-COHb concentrations was examined by using a plot of arteriovenous differences against the mean of the two measurements. INTERVENTION: We simultaneously sampled arterial, mixed venous, and internal jugular blood every 30 mins over the 6-hr study period. RESULTS: Two hundred fifty arterial and mixed venous COHb concentrations were obtained, and 214 internal jugular COHb concentrations were obtained. One hundred additional arterial, mixed venous, internal jugular, and peripheral COHb concentrations were obtained. Correlation between samples at each concentration revealed r2 > = .94. CONCLUSION: Venous COHb concentrations predict arterial COHb concentrations with a high degree of accuracy and are correlated at low, moderate, and high concentrations of carbon monoxide exposure. Arterial or venous samples can be used to accurately measure COHb concentrations.     

Intrinsic function of S100A8/A9 complex as an anti-inflammatory protein in liver injury induced by lipopolysaccharide in rats

BACKGROUND: We hypothesized that the S100A8/A9 complex is effective in the suppression of acute inflammatory changes. METHODS: To clarify such a functional role of the S100A8/A9 complex in acute inflammatory disorder, the complex purified from human leukocytes (approx. 1 mg) was intraperitoneally injected into rats 1.0 or 3.5 h after an injection of lipopolysaccharide (LPS). RESULTS: The serum concentrations of interleukin-6 (IL-6) and nitric oxide (NOx) were significantly decreased in the treated rats. Conversely, when anti-S100A8/A9 complex IgG was injected into the tail blood vessel of a rat 1.0 h after the injection of LPS, the serum concentration of IL-6 increased slightly, indicating that the antibody immunoregulatorily blocked the activity of the complex as an anti-inflammatory protein in vivo. In addition, the S100A8/A9 complex bound non-specifically with interleukin-1beta (IL-1beta), IL-6 and TNF-alpha in vitro, suggesting that the complex could bind with these cytokines in vivo. A large number of endogenous S100A8/A9 complex-positive cells that accumulated in the inflamed region in the liver 6 h after the injection of LPS were microscopically observed, while apparent inflammatory changes were not found microscopically in other organs, such as the kidney, lung and spleen. In rats treated with the S100A8/A9 complex, neither acute inflammatory changes nor S100A8/A9 complex-positive cells were also observed microscopically in the liver tissue. CONCLUSIONS: These findings suggest that the S100A8/A9 complex indirectly suppresses the overproduction of NOx from activated neutrophils and/or macrophages by neutralizing the activity of pro-inflammatory cytokines. Thus, the S100A8/A9 complex may play an important role in the suppression of acute inflammation by modulating the vital activity of pro-inflammatory cytokines in vivo.     

Activation of innate immunity in patients with venous thrombosis: the Leiden Thrombophilia Study.

BACKGROUND: Previous studies have suggested that levels of inflammatory mediators are risk indicators for venous thrombotic disease. We have sought to confirm and extend these findings by measuring plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12p70 levels in a case-control study for venous thrombotic disease. METHODS: The plasma levels of these inflammatory mediators were measured by flow cytometric analysis using a multiplexed bead assay. Patient and control samples came from the Leiden Thrombophilia Study (474 controls and 474 patients). RESULTS: In a subset of patients and controls inflammatory mediators are detectable in plasma. The crude odds ratios (ORs) associated with the presence of detectable markers were 2.1 [TNF-alpha, 95% confidence interval (CI) 1.1, 3.9], 1.7 (IL-1beta, 95% CI 1.1, 2.9), 2.4 (IL-6, 95% CI 1.9, 5.3), 2.8 (IL-8, 95% CI 1.8, 4.4), 0.8 (IL-10, 95% CI 0.3, 1.8), and 1.3 (IL-12p70, 95% CI 0.9, 2.0). Adjustment for putative confounders did not influence the risk estimates. CONCLUSION: TNF-alpha, IL-6, and IL-8 levels are risk determinants for venous thrombosis. Individuals with detectable levels of either of these mediators in plasma have an OR of about 2. In line with these findings, the odds for the anti-inflammatory cytokine Il-10 tend to be < 1. These results add further evidence for the contention that there is an inflammatory component to venous thrombotic disease and may explain why anti-inflammatory agents such as aspirin may be effective for prevention.     

内毒素致伤大鼠肺组织促炎与抗炎细胞因子mRNA表达的时相性研究

目的 研究不同剂量内毒素致伤大鼠肺组织促炎和抗炎细胞因子mRNA表达的时相性,并探讨这些细胞因子在全身炎症反应失控和急性肺损伤中的可能作用。方法 采用逆转录-聚合酶链反应(RT-PCR)检测不同剂量脂多糖(LPS)致伤大鼠肺组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、IL-4、IL-10和IL-13的mRNA表达。结果 随着LPS剂量增加,TNF-α、IL-1β、IL-6、IL-4、IL-10和IL-13的mRNA表达均增强(与生理盐水对照组比较,P均<0.01);LPS≥6 mg/kg组上述细胞因子表达显著高于此剂量以下组(P均<0.01)。表达峰值时间:TNF-α为1 h,IL-6为4 h,其他均在2 h。结论 内毒素致急性肺损伤中,TNF-α是早期表达的促炎细胞因子,而IL-6在炎症进一步发展中发挥作用;抗炎细胞因子IL-4、IL-10、IL-13高表达亦可能促进炎症的放大而不是起保护作用。     

重组白细胞介素-10/Fc融合蛋白对内毒素诱导急性肺损伤小鼠的实验干预作用

目的 探讨重组白细胞介素-10(rIL-10)/Fc融合蛋白对内毒素诱导的急性肺损伤(ALl)小鼠炎症调控作用及其机制.方法 向气管内注射脂多糖(LPS)制成ALl动物模型;rIL-10/Fc融合蛋白采用腹腔内给药方式.132只小鼠被随机均分为正常对照组、rIL-10/Fc对照组、ALl模型组、rIL-10/Fc治疗组.每组选择25只小鼠观察24 h存活率;其余用于检测支气管肺泡灌洗液(BALF)中自细胞数量,肿瘤坏死因子-a(TNF-a)和IL-1β水平,以及肺组织髓过氧化物酶(MPO)活性、肺组织湿/干重(W/D)比值;光镜下观察肺组织病理学改变.结果 注射LPS后4 h可引起BALF中TNF-a和IL-1β显著升高(P均＜0.01),rIL-10/Fc治疗组较ALI模型组有所降低,但差异无统计学意义;但在8 h和12 h,rIL-10/Fc融合蛋白能显著抑制BALF中TNF-a产生,在12 h抑制IL-1β产生;并明显改善LPS注射24 h后实验动物的存活率(P＜0.01).rIL-10/Fc对LPS诱导的ALI小鼠BALF中白细胞数量、肺组织MPO活性、肺组织W/D比值无显著改变.注射LPS 24 h后,肺组织出现了明显的炎性改变,但在rlL-10/Fc融合蛋白干预后没有出现显著的差异.结论 rIL-10/Fc融合蛋白能显著抑制LPS诱导的ALI小鼠肺促炎细胞因子产生,改善预后.     

急性滑膜炎患者血清CRP、PCT和IL-6表达及临床特点

目的探讨急性滑膜炎患者血清C反应蛋白(CRP)、降钙素原(PCT)和白细胞介素-6(IL-6)水平变化情况,同时观察急性滑膜炎的临床特点。方法选取2015年10月至2018年6月在该院住院治疗的滑膜炎患者120例作为研究对象,依据关节腔有无积液形成分为积液组(60例)和非积液组(60例),另选取60例健康志愿者作为对照组。采用免疫比浊法检测CRP水平,酶联免疫吸附试验检测IL-6水平,荧光免疫定量分析法检测PCT水平;同时分析其病因和病变部位等特征。结果病因分析发现,滑膜炎以创伤性(35.83%)为主要病因,其次为退行性增生病变(19.17%)。积液组和非积液组患者CRP、IL-6、PCT水平均明显高于对照组,差异均有统计学意义(P<0.01);积液组患者CRP、IL-6、PCT水平均高于非积液组,差异均有统计学意义(P<0.05)。CRP、PCT、IL-6水平诊断滑膜炎的受试者工作特征曲线下面积(AUC)分别为0.719、0.785、0.726,三者AUC差异均有统计学意义(P<0.01)。膝关节是发病最频繁的部位,其次是髋关节。结论急性滑膜炎以创伤性为主,主要累及部位为膝关节,血清CRP、IL-6及PCT水平与滑膜急性炎性反应存在一定关系,可作为评估炎性反应程度的初筛指标,对于观察病情变化和疗效有一定临床价值。     

Hemoglobin stimulates the release of proinflammatory cytokines from leukocytes in whole blood

Isolated mononuclear leukocytes, when incubated with purified hemoglobin Ao (HbAo), release the proinflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha). In this study we examined whether leukocytes in whole blood, when incubated with HbAo, release IL-8, TNF-alpha, and IL-6. Leukocytes in whole blood incubated with HbAo for 4 hours at 37 degrees C, 5% CO2, and 95% humidity released 187, 1313, and 50 pg/mL of IL-6, IL-8, and TNF-alpha, respectively, as compared with 6, 192, and 2 pg/mL released by leukocytes in blood incubated with human serum albumin (HSA). Furthermore, plasma from blood incubated with HbAo exhibited chemotactic activity and stimulated human umbilical vein endothelial cells to become adherent to neutrophils. These activities were 3.3 and 2.6 times those measured in plasma from blood incubated with HSA. Hydrocortisone (0.05 micromol/L to 50 micromol/L) inhibited cytokine release in a dose-dependent manner with ED50 values of 0.23 micromol/L, 0.19 micromol/L, and 0.10 micromol/L for IL-6, IL-8, and TNF-alpha, respectively. The release of proinflammatory cytokines in whole blood after exposure to hemoglobin solutions is consistent with the possibility that an inflammatory reaction could develop on infusion of hemoglobin, whereas inhibition of cytokine release by hydrocortisone suggests that the inclusion of anti-inflammatory compounds in hemoglobin solutions may prevent undesirable effects caused by inflammation after infusion.     

Effects of polyenylphosphatidylcholine on cytokines,nitrite/nitrate levels,antioxidant activity and lipid peroxidation in rats with sepsis

OBJECTIVES: To determine the effect of pretreatment with polyenylphosphatidylcholine (lecithin, PPC) on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, total nitrite/nitrate (NOx), and tissue levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in septic rats. DESIGN: Prospective, randomized, controlled animal study. SETTING: University laboratory. SUBJECTS: Forty-five Spraque-Dawley rats were divided into three groups: group C, sham-operated; group S, sepsis; and group P, sepsis pretreated with PPC. INTERVENTIONS: Rats were made septic by cecal ligation and puncture (CLP). Group P rats were treated with PPC (100 mg/day orally) for 10 days before sepsis. Twenty-four hours later CLP, plasma concentrations of TNF-alpha, IL-6 and IL-10 and plasma levels of NOx were measured. SOD and MDA were determined in liver, lung and heart homogenates. MEASUREMENTS AND MAIN RESULTS: All rats in group P survived during the 24-h observation time after CLP, whereas survival rate in group S was 66.7% (10/15; P<0.05). PPC significantly reduced plasma levels of TNF-alpha (P=0.006), IL-6 (P=0.007), IL-10 (P=0.016), NOx (P<0.001), and tissue levels of MDA (P<0.001) in group P with respect to in group S. Tissue levels of SOD significantly increased in group P when compared with group S (P<0.001). CONCLUSIONS: These results show that PPC pretreatment exerts cumulative effects in decreasing the levels of cytokines, NOx, and tissue MDA concentrations, with a concomitant increase in survival in septic rats. Lecithin therapy may be a useful adjuvant therapy in controlling of the excessive production of the inflammatory cytokines in patients with severe sepsis. DESCRIPTOR: SIRS/sepsis, experimental studies.     

Inflammatory cytokines and their receptors in arterial and mixed venous blood before, during and after infusion of drained untreated blood

Wound blood for postoperative autologous transfusion is drained through an area of damaged tissue, the surgical wound, and contains inflammatory mediators. The inflammatory cytokines interleukin-1-beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) and their modulators interleukin-1-receptor antagonist (IL-1Ra), interleukin 6 soluble receptor (IL-6sR), soluble tumour necrosis factor receptor 1 (sTNF-R1) and interleukin 10 (IL-10), together with white cell count (WCC) and white cell differential count were measured in arterial and mixed venous blood before, during and after infusion of postoperatively drained untreated blood in nine patients operated for thoracic scoliosis. We found a transient increase in IL-6, an increase in TNF-RI, an increase in IL-8 with granulocytosis and a decrease in IL-10 in the systemic circulation. The increase in IL-6 was higher in mixed venous than in arterial blood.     

Plasma interleukin-1beta, -6, -8 and tumor necrosis factor-alpha as highly informative markers of pelvic inflammatory disease

BACKGROUND: The role of proinflammatory cytokines in pelvic inflammatory disease (PID) is unclear. We therefore determined whether plasma proinflammatory cytokines, interleukin-1beta (IL-1beta), IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were useful plasma markers in PID patients. METHODS: Multiplex bead array analysis was used to measure the plasma levels of proinflammatory cytokines in 50 healthy controls as well as in 41 PID patients before and after routine protocol treatments. RESULTS: IL-1beta, IL-6, IL-8 and TNF-alpha were significantly elevated in PID patients before antibiotic treatment than after treatment. However, IL-8 was not significantly different between healthy controls and PID patients. The relative increase in ratio of IL-6 was significantly correlated with white blood cell count (r=0.448, p=0.003), neutrophil count (r=0.472, p=0.002) and C-reactive protein level (r=0.412, p=0.008). CONCLUSIONS: IL-1beta, IL-6, IL-8 and TNF-alpha may play an important role in the pathogenesis of PID. These biomarkers, particularly IL-6, could be useful adjuncts for the clinical diagnosis of PID.     

Induction of systemic serum procalcitonin and cardiocirculatory reactions after isolated limb perfusion with recombinant human tumor necrosis factor-alpha and melphalan

OBJECTIVES: Isolated, hyperthermic limb perfusion (ILP) with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) and melphalan is a highly effective treatment for locoregional metastases of malignant melanoma and for advanced soft tissue sarcoma of the limb. The major systemic side effects are characterized by the induction of a systemic inflammatory response syndrome (SIRS). Procalcitonin (PCT), a serum marker of bacterial sepsis, was investigated with respect to its role in SIRS after ILP. SETTING: University surgical oncology division with an integrated eight-bed intensive care unit. PATIENTS: Thirty-seven patients were treated by ILP with rhTNF-alpha and melphalan (n = 26) or with cytostatics alone (n = 11) for soft tissue sarcoma or malignant melanoma. INTERVENTIONS: The course of serum PCT, interleukin (IL)-6, and IL-8 was analyzed intra- and postoperatively. Hemodynamic variables including heart rate, mean arterial pressure, cardiac index, pulmonary arterial pressure, pulmonary capillary occlusion pressure, and pulmonary and systemic vascular resistance were recorded in parallel. MEASUREMENTS AND MAIN RESULTS: PCT was significantly elevated over baseline after ILP with a maximum between 8 hrs (peak level 16.0+/-18.8 (SD) ng/mL) and 36 hrs (13.8+/-15.7 ng/mL) (p < .001). The increase in serum PCT was significantly more pronounced after ILP with rhTNF-alpha/melphalan than after ILP with cytostatics alone (p < .001). IL-6 and IL-8 were also significantly increased after ILP (p = .001), reaching peak concentrations at 1 hr and 4 hrs postoperatively. Significant changes in heart rate, mean arterial pressure, cardiac index, and systemic vascular resistance were observed during and after ILP; however, PCT levels could not be correlated to these variables. Pulmonary arterial pressure, pulmonary capillary occlusion pressure, and pulmonary vascular resistance showed no significant changes. CONCLUSIONS: Serum procalcitonin is induced as part of the SIRS after ILP with rhTNF-alpha/melphalan. It may be induced directly by rhTNF-alpha or other cytokines, because serum peaks of IL-6 and IL-8 precede the peak of PCT. Because there is no correlation between serum levels of PCT and hemodynamic variables, this marker cannot be applied to assess the severity of SIRS reaction after ILP.     

Discrimination of sepsis and systemic inflammatory response syndrome by determination of circulating plasma concentrations of procalcitonin, protein complement 3a, and interleukin-6

OBJECTIVE: To evaluate whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte elastase (elastase), and the C-reactive protein (CRP) determined directly after the clinical onset of sepsis or systemic inflammatory response syndrome (SIRS) discriminate between patients suffering from sepsis or SIRS and predict the outcome of these patients. DESIGN: Prospective study. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Twenty-two patients with sepsis and 11 patients with SIRS. MEASUREMENTS AND MAIN RESULTS: The plasma concentrations of PCT, C3a, and IL-6 obtained < or =8 hrs after clinical onset of sepsis or SIRS but not those of elastase or CRP were significantly higher in septic patients (PCT: median, 16.8 ng/mL, range, 0.9-351.2 ng/mL, p = .003; C3a: median, 807 ng/mL, range, 422-4788 ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5-1004 pg/mL, p = .009, all Mann-Whitney rank sum test) compared with patients suffering from SIRS (PCT: median, 3.0 ng/mL, range, 0.7-29.5 ng/mL; C3a: median, 409 ng/mL, range, 279566 ng/mL; IL-6: median, 98 pg/mL, range, 23-586 pg/mL). The power of PCT, C3a, and IL-6 to discriminate between septic and SIRS patients was determined in a receiver operating characteristic analysis. C3a was the best variable to differentiate between both populations with a maximal sensitivity of 86% and a specificity of 80%. An even better discrimination (i.e., a maximal sensitivity of 91% and a specificity of 80%) was achieved when PCT and C3a were combined in a "sepsis score." C3a concentrations also helped to predict the outcome of patients. Based on the sepsis score, a logistic regression model was developed that allows a convenient and reliable determination of the probability of an individual patient to suffer from sepsis or SIRS. CONCLUSIONS: Our data show that the determination of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients than the variables CRP and elastase, routinely used at the intensive care unit. The determination of PCT and C3a plasma concentrations appears to be helpful for an early assessment of septic and SIRS patients in intensive care.     

Sensitivity and specificity of various markers of inflammation for the prediction of tumor necrosis factor-alpha and interleukin-6 in patients with sepsis.

OBJECTIVES: To determine correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein [CRP], and procalcitonin [PCT]) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients. DESIGN: Prospective consecutive case series. SETTING: Surgical intensive care unit (ICU) of a university hospital. PATIENTS: A total of 175 patients experiencing intensive care unit stays >48 hrs categorized for sepsis according to ACCP/ SCCM Consensus Conference criteria. MEASUREMENTS AND MAIN RESULTS: CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area-under-the-curve of the receiver operating characteristics curves, predicting capability was highest for PCT (0.814 for TNF-alpha >40 pg/mL and 0.794 for IL-6 >500 pg/mL), moderate with CRP (0.732 and 0.716, respectively), and lowest for leukocyte count (0.493 and 0.483, respectively) and body temperature (0.587 and 0.589, respectively). Sensitivity, specificity, positive, and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest. CONCLUSION: PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.     

谷氨酰胺在体内/外对巨噬细胞炎症因子分泌的影响

目的 观察谷氨酰胺(Gln)在体内/外条件下对巨噬细胞炎症反应及热休克蛋白(HSP)表达的影响,探讨Gin在脓毒症时抑制体内炎症反应的机制.方法 实验 1:将培养的腹腔巨噬细胞株RAW264.7分为Gln 0、0.5和8 mmol/L 3组,分别于内毒素脂多糖(LPS)刺激后0、1、4、12和24 h收集细胞及上清液.实验2:45只昆明小鼠被随机均分为假手术(Sham)组、模型组、Gin组;采用盲肠结扎穿孔术(CLP)制备小鼠脓毒症模型,术后即刻从尾静脉注射Gin 0.75 g/kg(Gln组)或等量生理盐水(Sham组和模型组).6 h后采血,腹腔灌洗分离巨噬细胞.用酶联免疫吸附法(ELISA)检测细胞上清液、血清、巨噬细胞裂解液中肿瘤坏死因子-a(TNF-a)、白细胞介素-6(IL-6)、IL-10浓度;用蛋白质免疫印迹法检测巨噬细胞HSP72蛋白表达.结果 体外条件下Gin可显著促进RAW264.7细胞释放TNF-a,IL-6和IL-10,呈剂量和时间依赖性(P＜0.05或P＜0.01),LPS刺激4 h后,Gln 8 mmol/L组RAW264.7细胞HSP72表达显著增加(P均＜0.01).体内条件下,Gin组腹腔巨噬细胞TNF-a、IL-6含量均明显低于模型组(P＜0.01和P＜0.05),3组间IL-10含量比较差异无统计学意义;Gln组血清TNF-a浓度明显低于模型组(P＜0.05),两组血清IL-6、IL-10浓度差异无统计学意义;Gin组巨噬细胞HSP72表达较模型组和Sham组均显著升高(P均＜0.01).结论 Gin体外作用时可显著促进巨噬细胞释放TNF-a和IL-6,且该作用不能被HSP72表达所抑制.体内作用条件下Gln抑制腹腔巨噬细胞合成TNF-a和IL-6.体外和体内条件下Gln都可诱导巨噬细胞表达HSP72,提示HSP72表达可能不是Gln在脓毒症时抑制机体炎症反应的主要机制.     

Tobramycin Nebulizer Solution in severe COPD patients colonized with <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>: effects on bronchial Inflammation

INTRODUCTION: Airway colonization with Pseudomonas aeruginosa is frequent in severe chronic obstructive pulmonary disease (COPD) and may lead to progressive inflammatory damage. Inhaled Tobramycin Nebulizer Solution (TNS; a preservative-free formulation) is an effective therapy in chronic P aeruginosa infection in cystic fibrosis and bronchiectasis. In this study we aimed to investigate the effects of a TNS short course on inflammatory markers in bronchial secretions from multiresistant P aeruginosa-colonized patients with severe COPD. To the authors' knowledge, this is the first study to examine this in cases of severe COPD. METHODS: Thirteen COPD patients (GOLD criteria 3-4; mean age 72.7+/- 8 years; mean basal forced expiratory volume in 1 second (FEV(1)) 34.8%+/-8.1%; mean FEV(1)/forced vital capacity 0.6+/-0.1) were enrolled. All patients were colonized with P aeruginosa and resistant to oral/intravenous specific antibiotics. Eosinophilic cationic protein (ECP), interleukin-1 beta (IL-1beta), interleukin-8 (IL-8), tumor necrosis factor alfa (TNF-alpha), and cell counts were measured in spontaneous secretions before and after a 2-week TNS course (300 mg twice daily). RESULTS: The TNS course induced a significant reduction in IL-1beta (P<0.03), IL-8 (P<0.02), ECP (P<0.01) concentrations, and in eosinophil count (P<0.01). TNF-alpha levels, and neutrophil and lymphocyte counts were not significantly affected. The second week of treatment proved crucial in terms of efficacy. P aeruginosa density was lowered after 6 months; severe acute exacerbations were reduced by 42%. CONCLUSION: TNS reduced the inflammatory impact of P aeruginosa in multiresistant, P aeruginosa-colonized patients with severe COPD. A therapeutic role for TNS can be strongly suggested in these particular conditions.     

血清炎性标志物在慢性阻塞性肺疾病急性加重期诊断中的价值

目的探讨联合检测血清炎性标志物降钙素原、白细胞介素-6、白细胞介素-8对慢性阻塞性肺疾病急性加重期细菌感染的诊断价值.方法将102例慢性阻塞性肺疾病急性加重期患者依据痰液中潜在病原菌浓度分为感染组52例和非感染组50例,选取同期20名健康志愿者设为对照组.检测比较3组治疗前后血清降钙素原、白细胞介素-6、白细胞介素-8水平.结果治疗前3组血清降钙素原、白细胞介素-6、白细胞介素-8水平比较差异有统计学意义(P<0.01),其中感染组血清降钙素原、白细胞介素-6、白细胞介素-8水平均显著高于非感染组和对照组(P<0.05或0.01),非感染组血清降钙素原、白细胞介素-6、白细胞介素-8水平与对照组比较差异无统计学意义(P>0.05);治疗后感染组血清降钙素原、白细胞介素-6、白细胞介素-8水平较治疗前显著下降(P<0.05),与对照组比较差异均无统计学意义(P>0.05).非感染组入组时血清降钙素原阳性检出10例(20.0%),白细胞介素-6、白细胞介素-8任意一项阳性检出17例(34.0%);感染组治疗前血清降钙素原阳性检出36例(69.2%),白细胞介素-6、白细胞介素-8任意一项阳性检出46例(88.5%).血清降钙素原阳性检出灵敏度为45.1%(46/102),白细胞介素-6、白细胞介素-8任意一项阳性检出灵敏度为61.8%(53/102).结论联合检测血清炎性标志物降钙素原、白细胞介素-6与白细胞介素-8水平有助于临床准确判断慢性阻塞性肺疾病急性加重期患者细菌感染状况,为合理应用抗生素提供科学依据.     

高容量血液滤过对脓毒症合并急性呼吸窘迫综合征血流动力学和氧代谢的影响

目的探讨连续性高容量血液滤过(HVHF)对严重脓毒症合并急性呼吸窘迫综合征(ARDS)的呼吸、血流动力学和氧代谢的影响。方法选择由各种病因导致的12例脓毒症并发ARDS患者,全部病例均在呼吸机支持下每日连续给予床边HVHF(置换液流量80ml·kg-1·h-1)治疗12~18h,观察治疗前后患者炎性介质〔肿瘤坏死因子α(TNFα)、白细胞介素6(IL6)、IL8、IL10〕、氧合指数(PaO2/FiO2)、急性生理学与慢性健康状况评分系统(APACHE)评分、多器官功能障碍综合征(MODS)评分和胸腔液体容量(TFC)的变化。通过Swan Ganz导管获得心排血量(CO)、外周循环阻力(SVR)、肺循环阻力(PVR)、平均肺动脉压(MPAP)、肺动脉楔压(PAWP)、动脉血氧含量(CaO2)、混合静脉血氧含量(CvO2)、氧消耗(VO2)、氧输送(DO2)和氧摄取率(O2ER)。结果HVHF48h后的MPAP、PVR和TFC均明显下降(P均<0.05)。HVHF72h后,TNFα、IL6和IL8含量较HVHF前均明显下降(P均<0.05),DO2、O2ER和VO2逐渐稳定,并伴随动脉氧分压(PaO2)、PaO2/FiO2和气道峰压(Ppeak)的改善(P<0.05或P<0.01)。结论连续性HVHF可通过清除部分细胞因子,减少TFC,改善严重脓毒症合并ARDS患者的呼吸、血流动力学和氧代谢。     

Possible prognostic value of leukotriene B(4) in acute respiratory distress syndrome

OBJECTIVE: To study the major eicosanoids implicated in the pathophysiology of acute respiratory distress syndrome (ARDS) in order to estimate their relative prognostic values. METHODS: We conducted a prospective study in a consecutive series of patients with ARDS admitted to a university hospital intensive care unit. We measured the plasma concentrations of 3 inflammatory mediators (thromboxane B(2), 6-keto prostaglandin F(1alpha), and leukotriene B(4)) in peripheral arterial and mixed venous plasma samples. RESULTS: We studied 16 patients with ARDS, who had a mean alpha SD baseline ratio of P(aO(2)) to fraction of inspired oxygen (P(aO(2))/F(IO(2))) of 147 +/- 37 mm Hg and a mean +/- SD baseline lung injury score of 2.9 +/- 0.37. The plasma concentrations of thromboxane B(2), 6-keto prostaglandin F(1alpha), and leukotriene B(4) were greater than the general-population reference levels in both arterial and mixed venous plasma, but only leukotriene B(4) was higher in arterial plasma than in mixed venous plasma (401 +/- 297 pg/mL vs 316 +/- 206 pg/mL, p = 0.04). When we correlated the eicosanoid concentrations with specific indicators of clinical severity, we found correlations only between the baseline P((aO2))/F(IO(2)) and the arterial thromboxane B(2) level (r = -0.57, p = 0.02), the arterial leukotriene B(4) level (r = -0.59, p = 0.01), and the transpulmonary gradient of leukotriene B(4) level (r = -0.59, p = 0.01). We also found a correlation between the transpulmonary gradient of leukotriene B(4) and the lung injury score (r = 0.51, p = 0.04). The thromboxane B(2) concentration in arterial plasma and the leukotriene B(4) concentration in both arterial and mixed venous plasma were the only baseline plasma eicosanoid concentrations that predicted significant differences in outcome. When looking at the transpulmonary gradient of the eicosanoids studied, we found that only the gradient of leukotriene B(4) showed significant differences of clinical interest. Among survivors we observed practically no gradient (-4.9%), whereas among nonsurvivors we found a substantial positive gradient of 41.6% for the elevated arterial (post-pulmonary) values, compared with the pulmonary-artery (pre-pulmonary) values, and this difference was statistically significant (p = 0.02). CONCLUSIONS: The pro-inflammatory eicosanoid leukotriene B(4) showed the best correlation with lung-injury severity and outcome in patients with ARDS.     

Continuous administration of PBP-2- and PBP-3-specific beta-lactams causes higher cytokine responses in murine Pseudomonas aeruginosa and Escherichia coli sepsis

OBJECTIVES: Initial antibiotic treatment of severe infections can lead to clinical deterioration due to sudden endotoxin release and concomitant exaggerated inflammatory response. Antibiotic-induced morphological changes may contribute to this phenomenon. High-dose ceftazidime, which inhibits penicillin-binding protein (PBP)-1 in Gram-negative bacteria, causes quick bacteriolysis and low endotoxin release. Low-dose ceftazidime leads to PBP-3 inhibition, which causes bacterial filament formation, associated with high endotoxin releases. PBP-2-specific antibiotics induce spheroplasts, again associated with low endotoxin release. We hypothesized that antibiotic type, concentration and regimen influence bacterial morphology, endotoxin levels and inflammatory response. METHODS: Neutropenic mice with Escherichia coli or Pseudomonas aeruginosa sepsis were treated with ceftazidime or meropenem 10-320 mg/kg as an intravenous bolus or as continuous tail vein infusions of 0.1 mL/h. Four hours later, bacterial counts, morphology, plasma endotoxin, pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)] and antibiotic concentrations were measured. RESULTS: Continuous infusion of 80 mg/kg ceftazidime was the lowest dose preventing filaments in E. coli infections. Bolus treatment resulted in filament formation, irrespective of the dose. During continuous treatment, IL-6 and TNF-alpha concentrations were higher compared with bolus treatment and controls for both antibiotics and both strains. A clear relationship between cfu counts in muscle and circulating IL-6 was shown (r=- 0.579, P=0.007), suggesting that plasma IL-6 is a valuable indicator of bacterial killing at the infection site. CONCLUSIONS: Our findings show that not PBP affinity but the method of antibiotic administration is crucial during initial treatment of severe infections.     

配对血浆分离吸附联合血液滤过治疗多器官功能障碍综合征的实验及临床研究

目的探讨配对血浆分离吸附法（CPFA）联合连续性静-静脉血液滤过（CVVH）治疗多器官功能障碍综合征（MODS）伴急性肝功能衰竭（ALF）患者的临床疗效和安全性。方法应用CPFA＋CVVH技术对重症加强治疗病房（ICU）中11例MODS伴ALF患者进行38例次治疗，比较患者治疗前后的平均动脉压（MAP）、氧合指数（Pa02／FiO2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、IL-6、IL-8、肝功能、肾功能、全身炎症反应综合征（SIRS）评分、急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分及临床症状改善程度，同时观察治疗的不良反应，并进行治疗安全性评价。结果患者治疗后尿量较治疗前增多，黄疽减轻，发热、乏力、腹胀、食欲明显改善，精神好转，意识转清。治疗后MAP较治疗前上升了12mmHg（1mmHg=0．133kPa），PaO2／FiO2上升了40mmHg（P均＜0．05）；TNF-α、IL-1β、IL-6、IL-8均较治疗前明显降低（P均＜0．05），血清总胆红素、直接胆红素、血氨、血尿素氮、肌酐均明显下降（P均＜20．05）；SIRS、APACHEⅡ评分均较治疗前有不同程度的下降（P均＜0．05）。11例患者存活5例，存活率为45．5％；未发生出血、休克、过敏等并发症，患者耐受好。结论CPFA联合CVVH能有效清除炎症介质，改善MODS伴ALF患者的预后，且无明显不良反应。