Methods for determining "reference changes" from serial measurements: plasma lipid-bound sialic acid.

Lipid-bound sialic (neuraminic) acid (LSA) was measured in EDTA-treated plasma of 26 healthy subjects at three-month intervals for up to one year. The change in LSA concentration for consecutive measurements ranged from -54 to 42 mg/L (mean, -2.1 mg/L; SD, 19.6 mg/L; n = 56). The "reference change" for plasma LSA (+/- 2 SD), calculated from distribution of the differences, was +/- 39 mg/L. The 88th percentile of the intra-individual variance was 338 mg2/L2 and the mean variance was 159 mg2/L2. Using the homeostatic, autoregressive time-series model, a reference change of +/- 51 mg/L between two consecutive measurements was determined to be statistically significant (i.e., expected by chance no more than 5% of the time) in 88% of the healthy subjects. Only 73% of the healthy subjects would have had intra-individual variances corresponding to the reference change of +/- 39 mg/L according to the autoregressive model. The concentration of LSA in plasma was significantly decreased upon surgery in five of 10 patients with colorectal adenocarcinomas of Dukes stages A-C when we used +/- 39 mg/L as the reference change, but in only two of the 10 when we used +/- 51 mg/L as the reference change.