HA-1A in septic patients with ARDS: Results from the pivotal trial

Objective To evaluate the effects of HA-1A, a human monoclonal antiendotoxin antibody, in septic patients with ARDS.Design Substudy of a multicenter, double-blinded, placebo-controlled trial of HA-1A in septic patients.Patients 63 septic patients with ARDS at the time of study entry.Intervention A single intravenous injection of HA-1A (100 mg) or placebo.Results A quantitative radiographic score, the PaO₂/FIO₂ ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3, 5 and 7 days after treatment. The duration of endotracheal intubation did not differ between the two groups. 15 of 30 HA-1A treated patients (50%) and 23 of 33 placebo-treated patients (69.7%) died within 28 days. The daily mortality was always lower in the HA-1A group, but this difference was not statistically significant at 28 days. The 28-day survival curves for the two treatment groups adjusted by covariate analysis were not significantly different (p=0.07). Using logistic regression, a significant independent effect of HA-1A treatment was detected upon the early survival rate at 7 days (p=0.03) but not at 14 and 28 days.Conclusion A single injection of HA-1A in septic patients with ARDS did not reverse acute respiratory failure or improve long-term survival.This study was supported by a grant from Centocor Inc., Malvern, PA, USA     

Detection of gram-negative bacteraemia in early sepsis by a quantitative chromogenic and kinetic endotoxin assay

A kinetic chromogenic limulus test was carried out in order to investigate the possibility of a sensitive and specific detection of circulating endotoxin during the first 24 h of septic shock or severe sepsis in 76 patients. Two commercial kits, Whittaeker (W) and Chromogenix (C), were used. Blood culture was taken as a reference. At 1 : 10 plasma dilution (a currently used dilution in the end point limulus test) abnormal reaction kinetics were found in 13% and 41% of tests, for C and W respectively ( P  = 0.0008), resulting in unreliable results. Retesting plasma at a greater dilution, until the reaction kinetic was identical to calibration curve control values, gave similar results between the two kits and a better accuracy. Beyond a 0.5 EU mL⁻¹ endotoxin level, the probability of Gram-negative bacteraemia was high (sensitivity = 0.53 and 0.47; specificity = 0.95 and 0.93 for C and W respectively). This kinetic limulus amoebocyte lysate (LAL) test may be useful in therapeutic decisions for treatment of endotoxaemia.     

IgA型内毒素抗体与肝病患者的关系

为研究IgA型内毒素抗体与各型肝炎的关系,我们采用EIA法对慢性重型肝炎、肝硬变、慢性肝炎和急性肝炎患者各10例血清进行了IgA型内毒素抗体浓度的检测(均呈HBV-M阳性)。结果如下:慢性重型肝炎组、肝硬变组和慢性肝炎组阳性率分别为70％、60％和30％,急性肝炎组和正常人组一样均为0％。慢性重型肝炎组与急性肝炎组和正常     

Fever in rats after intravenousE. coli endotoxin administration

Summary In conscious unrestrained rats, at an ambient temperature of 22°C, oesophageal temperature was measured and temperature effect of single and repeated intravenous injection ofE. coli endotoxin was examined. The first injection of endotoxin in a dose of 10.0 g/rat did not change the rat body temperature. The second injection of this dose in the same animals repeated after 48 h produced fever. With following injections the fevers observed were less pronounced. The absence of fever after a single injection of endotoxin was accompanied by the rapid loss of pyretic activity of the rat plasma samples (bioassayed in rabbits). When fever was observed (48 h interval between endotoxin injections) the pyretic activity of the rat plasma remained unchanged for 90 min following endotoxin injection. It was concluded that after a single injection endotoxin is rapidly detoxified in the rat circulation while this process does not take place after the second endotoxin injection (48 h interval). The process of endotoxin detoxification can be depressed by the pretreatment with nitrogen mustard. Analysis of changes of skin temperature following endotoxin injections and the influence of aspirin on endotoxin-induced fever suggest that the fever observed was of central origin.     

抗菌药物诱导内毒素的产生及抗内毒素药物的研究进展

内毒素是革兰阴性菌的主要致病成分,抗菌药物在杀/抑菌的同时会诱导内毒素的产生,增加了疾病的治疗难度。体外实验、动物实验证实,抗菌药物诱导内毒素的产生与多种因素有关,提示在临床选用抗菌药物时应对药敏实验结果及其诱导内毒素释放的特性进行综合考虑。抗内毒素药物的研究近年取得了一些成效,其中中药制剂也显示了很好的抗内毒素作用,相信这类药物会有广阔的发展前景。     

梗阻性黄疸治疗前后内毒素、IL-6和IL-8水平的比较

目的观察梗阻性黄疸患者术前抗内毒素治疗对内毒素（endotoxin）、白细胞介素6（IL-6）、白细胞介素8（IL-8）的影响.方法50例梗阻性黄疸患者分三组,在术前分别给予一般手术治疗（OJ组）,口服胆盐（OJT1组）和静脉注射抗内毒素抗体（OJT2组）观察血浆内毒素（ET）、IL-6及IL-8含量变化.结果三组术前ET、IL-6和IL-8水平差异不显著;OJT1组和OJT2组用药后血浆ET水平均显著下降,明显低于OJ组（P＜0.01）,术后进一步降低;IL-6在术后14d显著降低（P＜0.01）,IL-8在术后7 d降低（P＜0.05）.结论术前应用胆盐和抗内毒素抗体可有效降低梗阻性黄疸患者围手术期血浆ET、IL-6及IL-8水平.     

中药抗内毒素活性初步筛选

目的：筛选抗大肠杆菌Ｏ１１１Ｂ４内毒素中药。方法：分别对１３４种清热中药的７０％醇提取物用细菌内毒素检查法作体外抗内毒素活性检测、对有抗内毒素作用的提取液分别作倍比稀释后重复实验,找出抗内毒素最低有效浓度。结果：１３４种中药中７５种不同程度的体外抗内毒素活性。结论：清热中药中有相当多数有不同程度的体外拮抗大肠杆菌Ｏ１１１Ｂ４内毒素作用。     

四季青水煎液体外抗内毒素、抗菌和体内抗炎作用

目的 研究四季青水煎液的抗内毒素、抗菌和抗炎作用,揭示四季青清热解毒作用的药效学特点。方法 采用体外鲎试剂凝集实验方法检测其抗内毒素作用;采用琼脂二倍稀释法测定四季青水煎液以及与头孢噻肟、左氧氟沙星和庆大霉素联合使用时对25株甲氧西林敏感金黄色葡萄球菌(MSSA)、耐甲氧西林金黄色葡萄球菌(MRSA)、产超广谱β-内酰胺酶(extended-spectrum β-lactamase, ESBLs)大肠埃希菌、非产ESBLs大肠埃希菌和铜绿假单胞菌的最低抑菌浓度(minimum inhibitory concentration, MIC);采用二甲苯致小鼠耳廓炎症肿胀法观察其抗炎作用。结果 四季青水煎液在生药浓度6.25~100mg/mL时具有抗内毒素作用;对受试菌株MSSA、MRSA的MIC范围均为8~33mg/mL,对产ESBLs大肠埃希菌及非产ESBLs大肠埃希菌的MIC范围均为33~>133mg/mL,对铜绿假单胞菌的MIC为33~133mg/mL;与头孢噻肟、左氧氟沙星和庆大霉素联合使用时抗菌活性有相加作用,分级抑菌浓度(fractional inhibitory concentration, FIC)指数范围为0.5相似文献