Endotoxemia in human septic shock.

It is generally agreed that there is an increased incidence of postoperative renal failure in patients with obstructive jaundice. The proposition that this may be due to endotoxin, and that the endotoxin may be absorbed from the patient's own bowel flora, has been investigated. The study was conducted in patients and in animals. Twenty-four patients with obstructive jaundice were studied. Sixteen had endotoxin in the portal blood at operation and 13 of these had peripheral endotoxaemia at the time of operation or developed it during the 72 hours following operation. Only 3 of the patients had a proved possible site of infective origin for the endotoxaemia, the remainder absorbing the endotoxin from their own gastro-intestinal organisms. Portal endotoxaemia occurred when the serum bilirubin was 8-5 mg/100 ml or greater. There was a highly significant decrease in mean endogenous creatinine clearance postoperatively in patients with endotoxaemia, and expression of this as a percentage postoperative fall compared with preoperative levels enhanced the significance. Jaundiced patients without endotoxaemia had no significant fall in endogenous creatinine clearance. Matched non-jaundiced control patients did not develop portal or peripheral endotoxaemia, and there was no significant fall in postoperative creatinine clearance. Experiments using animals showed that the absence of bile salts in the intestinal tract in obstructive jaundice allows endotoxin to be absorbed, and that this absorption can be prevented by the oral administration of bile salts. The therapeutic implications in patients are discussed.

Endotoxin, bile salts and renal function in obstructive jaundice

Endotoxins are potent pro-inflammatory substances present in several natural environments and in commercial house dust extracts. To investigate the possible effect of chronic endotoxin exposure on asthma, 28 patients with perennial chronic asthma (20 allergic to house dust mite and eight intrinsic asthmatics) were evaluated during a 4-month period (lung function, clinical and immunological criteria). At the same time, two house dust samples were collected from each patient's home to determine total house dust weight (mg/m2), endotoxin concentration and house dust mite antigen content (evaluated indirectly by guanine content with HPLC method). The mean (+/- s.d.) endotoxin concentration, as measured by quantitative Limulus assay was 2.59 (+/- 3.41) ng/mg house dust, ranging from 0.12 to 20 ng/mg. The mean guanine content was 0.13 (+/- 0.16) mg/100 mg house dust. There was no correlation between endotoxin and house dust mite concentrations. Patients were compared according to the low or high grade exposure to dust, endotoxins and guanine. Compared with patients with low grade (less than or equal to 5.6 ng/ml) exposure, subjects exposed to high endotoxin concentrations (greater than 5.6 ng/ml) showed a significant increase in dyspnea (median 2.6 vs 3.3; P less than 0.05) and treatment (median 14 vs 44.3; P less than 0.01) scores, oral corticosteroid (median 0.0 vs 13.5 mg/24 hr; P less than 0.01) and beta 2-mimetics (median four vs eight puffs/day; P less than 0.01) intake, and a significant decrease in FEV1/FVC (median 84.5 vs 67% of predicted value; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Domestic endotoxin exposure and clinical severity of asthma

The incidence of and mortality from gram-negative bacterial sepsis is increasing (I). The morbidity and mortality associated with infections caused by gram-negative . bacteria are considered to be related to the endotoxins present in the cell walls of these bacteria. Endotoxin-like materials have been isolated from other organisms; however, this review is concerned only with endotoxins from gram-negative bac­ teria. The chemical and biological properties of bacterial endotoxins have been under investigation for more than a century. During the past two decades more refined chemical methods for the extraction and purification of bacterial endotoxins have been developed. With the production of relatively pure materials, the biological properties have been defined in animal and human experiments. Although endotox­ ins have a myriad of biological activities that affect all systems of the body, no clear-cut molecular-biological basis for these activities is known. This review focuses on the chemical composition, methods of detection, and some of the biological properties of bacterial endotoxins, with 'particular emphasis on the effects of these agents in human beings.

Biology of endotoxin

Intestinal endotoxemia: Clinical significance

Lysates obtained from amoebocytes of Limulus polyphemus, the horseshoe crab, showed gel formation after the addition of bacterial endotoxin. In contrast to living gram-negative bacteria, viable gram-positive microorganisms did not cause gelation of lysate. Nevertheless, peptidoglycan isolated from the cell walls of various gram-positive organisms did induce the reaction. However, the activity of peptidoglycan was 1,000 to 400,000 times less than that of Escherichia coli lipopolysaccharide. After exposure to lysozyme, peptidoglycan no longer gelled amoebocyte lysate, therefore apparently excluding endotoxin contamination. Gelation of amoebocyte lysate by endotoxin or peptidoglycan was inhibited by different concentrations of sodium polystyrolsulfonate. Whereas these studies confirm the specificity of the Limulus test for bacterial endotoxins, they also indicate that other substances of bacterial origin should be investigated for their ability to gel amoebocyte lysate.

Berno Heymer

Papers

Investigations on the specificity of the Limulus test for the detection of endotoxin.