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Biomedical subjects

J S McConnell

Publications and source records attributed to J S McConnell.

9 recordsLinked to original sources
PubMed1990

Dissociation between Limulus neutralisation and in vivo protection in monoclonal antibodies directed against endotoxin core structures.

Studies with rough mutants of certain Gram-negative bacteria have indicated that monoclonal antibodies (mAbs) to endotoxin core can protect animals and man from endotoxic shock. We assessed the ability of such antibodies to neutralise endotoxin in the Limulus amoebocyte lysate (LAL) assay, and compared this to their protective effect in a murine model of endotoxic shock. We evaluated 11 mAbs raised against Salmonella minnesota R595. Endotoxin neutralisation in the LAL assay, expressed as 50% inhibition titres, ranged between 1/32 and 1/414. However, there was no apparent relationship between the titre required to produce 50% inhibition of LAL and its ability to protect mice from endotoxic shock. We conclude that LAL neutralisation appears unrelated to biological activity; in this system, LAL inhibition by mAb ascites cannot be used to predict protection in vivo.

Animals↗
PubMed1988

Endotoxemia in obstructive jaundice. Observations on cause and clinical significance.

Perioperative endotoxemia was detected in 24 of 40 patients who underwent operation for obstructive jaundice (bilirubin level greater than 5.8 mg/dl). Endotoxemia was associated with an increased admission serum bilirubin level (p less than 0.05) and white blood cell count (p less than 0.05) and a decreased hematocrit value (p less than 0.05), but there was no significant association with other established preoperative risk factors. Patients with preoperative endotoxemia had a decreased immunoglobulin M anti-J5 endotoxin titer (p less than 0.05) and a decreased serum bile acid concentration (p less than 0.05). Preoperative endotoxemia was associated with reduced creatinine clearance before and after operation (p less than 0.05). There was no association between endotoxemia and clinical sepsis, gram-negative infection, or small-bowel colonization. Patients who died had increased preoperative serum fibrin degradation products (p less than 0.05).

Cholestasis↗
PubMed1986

A randomized clinical trial of oral ursodeoxycholic acid in obstructive jaundice.

Forty patients with obstructive jaundice (bilirubin greater than 100 mumol/l) were entered into a randomized trial of oral ursodeoxycholic acid for 48 h before surgery versus no additional therapy. Pre-operative venous and operative portal total bile salt concentrations were higher in the bile salt treated patients (P less than 0.001). Portal endotoxaemia during operation was reduced in ursodeoxycholic acid treated patients (P less than 0.05). There was no significant difference in systemic venous endotoxaemia, renal function or postoperative morbidity or mortality. This study suggests pre-operative oral bile salt therapy may be of no clinical benefit in patients with obstructive jaundice.

Administration, Oral↗
PubMed1986

Release of endotoxin from bacteria exposed to ciprofloxacin and its prevention with polymyxin B.

An in vitro system for studying the phenomenon of antibiotic-induced release of endotoxin from gram-negative bacteria is described. Endotoxin was measured by a quantitative limulus lysate microassay. Using a strain of Escherichia coli, ciprofloxacin was shown to cause an immediate and sustained increase in endotoxin release compared to control cultures whereas gentamicin did not, despite an equally rapid bactericidal effect. The potential value of the anti-endotoxin effect of polymyxin B was examined using a polymyxin B resistant strain of Klebsiella aerogenes. Ciprofloxacin alone caused endotoxin release, but when given with polymyxin B significantly less endotoxin was detected. These results indicate that in antibiotic-induced endotoxin release, the rate of cell death is less important than the site of antibiotic effect, and suggest that ciprofloxacin may act directly on the cell wall as well as on DNA gyrase. It is possible that polymyxin B could be used to reduce the extent of endotoxin release, and that this would be of clinical benefit.

Cell Wall↗
PubMed1985

Effect of anticoagulants on the chromogenic Limulus lysate assay for endotoxin.

We have examined the effects of anticoagulants on the chromogenic Limulus lysate assay for endotoxin. The results indicate that both heparin and CPD Adenine 1 have a striking dose related inhibitory effect on the assay. At concentrations of heparin as low as about 30 U/ml there was a 90% reduction in detectable endotoxin. The inhibitory effect of up to 100 U/ml of heparin could be neutralised by the addition of protamine sulphate. Anticoagulants appear to be an additional factor which can adversely affect the Limulus chromogenic assay for endotoxin. This further emphasises the need for alternative approaches to the measurement of endotoxin.

Adenine↗
PubMed1984

Observations on the measurement and evaluation of endotoxemia by a quantitative limulus lysate microassay.

A quantitative microassay for bacterial endotoxin in whole blood, based on Limulus amebocyte lysate gelation and involving the use of a chromogenic substrate, was studied. The lower limit of detection was 10 pg/ml, and the mean level of recovery from plasma spiked with 1 ng of endotoxin/ml was 0.93 ng/ml. At clinically significant levels endotoxin was more easily recovered from plasma than from serum. Platelet binding had no adverse effect on the assay. Despite the use of conventional methods for the removal of nonspecific activators and inhibitors, simultaneous assay of six specimens spiked with the same amount of endotoxin resulted in variation in recovery by greater than 100%. These experiments may explain in part the conflicting results of studies of endotoxemia in humans.

Endotoxins↗