Biomedical subjects

J E Marsh

Publications and source records attributed to J E Marsh.

4 recordsLinked to original sources

PubMed2001

Intrarenal synthesis of complement.

During the past decade, research has shown that the kidney has the capacity to synthesize most of the activation pathway components of the complement cascade. As well as implying physiological roles in local clearance of immune complexes and defense against invasive organisms, an increasing amount of evidence indicates that the intrarenal synthesis of complement makes an important contribution in the pathogenesis of renal injury. Here we review this evidence and present a case for more definitive investigation of these functions.

Animals↗

PubMed2000

Predominant role for C5b-9 in renal ischemia/reperfusion injury.

Previous work has indicated that complement is a mediator of ischemia/reperfusion (I/R) injury. To investigate the components of complement responsible for this effect, we examined a model of renal I/R injury in C3-, C4-, C5-, and C6-deficient mice. We occluded the renal arteries and veins (40-58 minutes) and, after reperfusion (0-72 hours), assessed renal structural and functional injury. C3-, C5-, and C6-deficient mice were protected from renal I/R injury, whereas C4-deficient mice were not protected. C6-deficient mice treated with antibody to block C5a generation showed no additional protection from I/R injury. Reconstitution with C6 alone restored the I/R injury in C6-deficient mice. Tubular epithelial cells were the main structures damaged by complement-mediated attack, and, in contrast, the renal vessels were spared. Neutrophil infiltration and myeloperoxidase activity were reduced in C-deficient mouse kidney, but by a similar extent in C3-deficient and C6-deficient mice. We conclude that the membrane attack complex of complement (in which C5 and C6 participate) may account for the effect of complement on mouse renal I/R injury. Neither C5a-mediated neutrophil infiltration nor the classic pathway, in which C4 participates, appears to contribute to I/R injury in this model. By contrast with other organs, such as the heart, the primary effect of complement in the ischemic area is on the parenchymal cell rather than the vascular endothelial cell. The membrane attack complex of complement is a potential target for prevention of I/R injury in this model.

Animals↗

PubMed1999

Targeting the complement system.

Interest has blossomed in the development of complement inhibitors, in parallel with a growth in our understanding of the biology of the complement cascade. The first generation of designed inhibitors was based on naturally occurring complement receptors and regulatory molecules. These agents provided useful tools for exploring the role of complement in experimental models of disease, but may have limited therapeutic application in humans because of their short half-lives, limited bioavailability and possible antigenicity. More recently, humanized antibodies and synthetic molecules that block the activation of complement have been developed, which look as though they may overcome some of these difficulties. The possibility for precision inhibition of a limited part of the complement cascade, or for inhibition confined to a single organ, may offer effective therapeutic results, while avoiding the disadvantages of nonselective complement blockade. This review examines the recent evidence that complement inhibition will reduce tissue damage resulting from organ transplantation, ischaemia-reperfusion injury, cancer, glomerulonephritis and the use of extracorporeal circuits.

Animals↗

PubMed1992

Early tracheal intubation with thiopentone in elective surgery.

We have studied tracheal intubating conditions within 30 s of administration of thiopentone in 24 patients and compared this with our usual method of tracheal intubation, which involves 3 min of manual ventilation in 29 patients. All patients received papaveretum 10 mg 3 min before induction and alcuronium at induction of anaesthesia. Satisfactory intubating conditions were observed in 83% of patients in both groups. There were no difficult or failed intubations and no patient had laryngospasm. The duration of laryngoscopy in the control group was 14.1 (SD 8.6) s (range 7-50 s), compared with 12.4 (3.1) s (range 6-20 s), in the early intubation group (ns). In the control group there was a significant decrease in systolic pressure before tracheal intubation and a significant increase in heart rate after intubation, compared with baseline values. The average systolic pressure in the early intubation group increased only minimally: from a pre-intubation value of 143.3 (21.2) mm Hg to 145.5 (25.1) mm Hg after intubation. Our results demonstrate that early tracheal intubation under thiopentone supplemented with an opioid and a non-depolarizing neuromuscular block is feasible, associated with minimal changes in arterial pressure and not accompanied by an increased incidence of side effects.

Adult↗