Determination of cyclosporine concentrations with monoclonal antibodies.

We measured cyclosporine in whole blood from normal volunteers administered single oral doses of the drug and from two renal-transplant patients on immunosuppressive maintenance therapy, by liquid chromatography (I) and by radioimmunoassay with use of nonspecific polyclonal (II), specific monoclonal (III), and nonspecific monoclonal (IV) antibodies. Concentrations determined by III were equivalent to I, irrespective of cyclosporine dose, concentration, time after dose, or time after transplant. Concentrations determined by II and IV were consistently higher than those by I, owing to cross reactivity with metabolites. Ratios of values by II and IV to those by I increased from less than 1.5 to about 3-4 between 0.5 and 12 h after a single cyclosporine dose, owing to differences in rates of appearance and disappearance of cyclosporine and cross-reacting metabolites, though for the constant 12-h dose intervals in the two renal-transplant patients at steady state these ratios (most within the range 3-4) were relatively stable. Ratios of concentrations measured by IV to those by II (mean of 1.2 for single-dose data, most within the range of 1.2 to 1.5 at steady state) were unaffected by time after dose or time after transplant, suggesting that, despite certain cross-reactivity differences between the two nonspecific antibodies, results are proportional throughout therapy. We therefore propose that III and IV offer alternatives, respectively, to the currently used I and II for cyclosporine monitoring.

Leucocyte ascorbate levels and postoperative deep venous thrombosis.

Forty-four general surgical patients were included in a prospective, randomized double-blind controlled trial of ascorbic acid (500 mg b.d.) or placebo for 7 days before operation. This was to test the hypothesis that vitamin C may reduce the instance of deep venous thrombosis postoperatively. Venous blood samples were taken before entering the trial, just immediately before surgery, on the day of operation and on three further occasions at 3-day intervals postoperatively for leucocyte ascorbic acid concentration (LAC). Venous thrombosis was diagnosed using the 125I-fibrinogen test and the leg scans interpreted by Roberts' criteria. There was no significant difference in the incidence of DVT between the treatment and placebo groups. In those with DVT (n = 23) the mean LAC on the day of operation was not significantly different from that in those without DVT. However, on the sixth and ninth postoperative days LAC levels were significantly lower in the DVT group. These results suggest that the administration of ascorbic acid preoperatively does not reduce the incidence of DVT, but a striking decrease in the LAC levels in the DVT patients is in keeping with the hypothesis that the initial event in the pathogenesis of DVT is adherence of leucocytes to the venous endothelium.