Quality of lipid and lipoprotein measurements in community laboratories.

OBJECTIVE: To determine the reliability of cholesterol and lipoprotein measurements conducted in local community laboratories. METHODS: Standardized duplicate serum aliquots at three concentrations (low, intermediate, and high) of total cholesterol, triglycerides, and high-density lipoprotein cholesterol were sent to 21 laboratories used by the physicians participating in the Cholesterol-Lowering Intervention Program. Results obtained from the laboratories were compared with values obtained from the Centers for Disease Control and Prevention-standardized Heinz Lipid Laboratory and with the means of the entire sample. RESULTS: The mean coefficient of variation (CV) was 1.3% or less for all three levels of total cholesterol, which demonstrates a high degree of precision. Accuracy was also high; over 80% of all laboratories were within 5% of the Heinz Laboratory low reference value, and all were within the 5% range for the medium and high samples. The CVs for triglycerides (< 2.3%) and high-density lipoprotein cholesterol (< 2.2%) were similar to that for total cholesterol, but up to 56% and 61% of the values fell outside the Heinz reference range for high-density lipoprotein cholesterol (intermediate concentration) and triglycerides (low concentration), respectively. As the Heinz Laboratory has a negative 2.7% bias versus the Centers for Disease Control and Prevention for total cholesterol and high-density lipoprotein cholesterol measurements, a higher percentage of laboratories fell outside the Centers for Disease Control and Prevention range. For medium and high total cholesterol samples, 16% of the laboratories were outside the 5% Centers for Disease Control and Prevention range, and the value was 58% for the low total cholesterol sample. For high-density lipoprotein cholesterol the percentages were 61%, 56%, and 39% for the low, medium, and high samples, respectively. CONCLUSIONS: These data suggest that according to the standards set by the National Cholesterol Education Program Laboratory Standardization Panel, reliability of total cholesterol measurements in local laboratories is high. Lower levels of accuracy were noted for triglycerides and high-density lipoprotein cholesterol measurements.

Effect of sample storage on quantitation of lipoprotein(a) by an enzyme-linked immunosorbent assay.

This study evaluated the effect of storage on the quantitation of lipoprotein (Lp)(a) in 25 serum samples. Aliquots of serum were stored for up to three years at either -20 degrees C or -70 degrees C and Lp(a) subsequently analyzed using an enzyme-linked immunosorbent assay kit. Concentrations of Lp(a) declined during storage, and the temperatures employed elicited significantly different (P < 0.05) values within 12 mon which further diverged during three years of storage. Compared to baseline values, significant decreases (P < 0.05) in Lp(a) levels were evident after six months of storage at -20 degrees C with apparent losses (geometric mean) reaching 36.9% (95% confidence interval: 30.9%, 42.9%) after three years. Similarly, significantly lower (P < 0.05) Lp(a) values were recorded after six months of storage at -70 degrees C and at three years the decrease (geometric mean) was 19.1% (95% confidence interval: 14.3%, 24.0%). The losses, after three years, in terms of the arithmetic mean were 53.5 and 26.2% at -20 and -70 degrees C, respectively. Phenotype analysis suggested that large isoforms are more susceptible to degradation than smaller moieties. This may be related to the observation that apparent losses are reduced in samples containing over 8 mg/dL Lp(a). Nevertheless, Lp(a) levels in stored samples retained a strong correlation with the baseline values. These results must be considered specific for the storage conditions and analytical procedures employed.

Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum.

OBJECTIVE: We tested the hypothesis that serum free (nonesterified) fatty acid and triglyceride concentrations are increased in nulliparous women with preeclampsia relative to women with uncomplicated pregnancies and that these lipids decrease post partum, consistent with the known resolution of clinical symptoms. The relationships between serum concentrations of these lipids and the lipid peroxidation metabolite malondialdehyde were also examined. STUDY DESIGN: Predelivery and 24 to 48 hour postpartum venous blood samples were collected from eight women with preeclampsia and nine women with uncomplicated pregnancies after an 8- to 10-hour fast. Sera were analyzed for concentrations of triglycerides, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and malondialdehyde. RESULTS: Antepartum serum triglyceride and free fatty acid concentrations were increased approximately twofold in women with preeclampsia relative to uncomplicated pregnancies (p <0.02 and 0.004, respectively). Total, high-density lipoprotein, and low-density lipoprotein cholesterol concentrations did not differ between groups. Concentrations of all lipids decreased significantly in both groups within 48 hours post partum. However, triglyceride and free fatty acid concentrations remained higher in women with preeclampsia (p<0.006, both variables). Triglyceride and free fatty acid concentrations correlated positively, both ante partum (R2 0.42, p<0.01) and post partum (R2 0.39, p<0.02). Antepartum concentrations of malondialdehyde were 50% higher in women with preeclampsia (p<0.01) and decreased post partum (p <0.02) but did not decrease in controls (p = 0.07). Antepartum serum triglycerides and free fatty acids correlated positively with malondialdehyde concentrations (R2 0.38, p <0.02, both cases). CONCLUSION: Triglycerides and free fatty acids, but not cholesterol, are increased in preeclampsia and correlate with the lipid peroxidation metabolite malondialdehyde. We speculate that these interactions may contribute to endothelial cell dysfunction in preeclampsia.

Use of hexyl isocyanate antigen to detect antibodies to hexamethylene diisocyanate (HDI) in sensitized guinea pigs and in a sensitized worker.

Hypersensitivity to hexamethylene diisocyanate (HDI) has been reported following occupational exposure. Diagnosis of sensitivity is usually made from clinical evaluation of symptomatology. An in vitro serologic assay for HDI sensitivity was developed by immunizing guinea pigs with HDI and with hexyl isocyanate (HMI). Animals injected intradermally with HMI produced hapten-specific antibodies whereas guinea pigs injected with HDI produced antibodies specific for larger determinants which included the HDI hapten. The larger determinants were assumed to be composed of portions of "self" molecules which reacted in vivo with HDI. Serum albumin appeared to be one such molecule. No cross reactions were noted between antibodies to HDI and another widely used industrial isocyanate, toluene diisocyanate (TDI). Antigens effective in detecting antibodies to HDI or HMI were tested for ability to detect reaginic antibodies in a worker with clinical "HDI" asthma. Using a radioimmunoassay (RAST), antibodies reacted with conjugates containing either HDI or HMI as haptens. In addition, the prevalance of HDI polyisocyanates (Desmodur N) in spray paints prompted its use as a hapten. Antibodies reacted with Desmodur N antigen conjugates in RAST. RAST inhibition further indicated that Desmodur N antigen reacted more readily with the patient's antibodies than did HDI or HMI antigens. These results suggest that the patient may have been exposed to HDI polyisocyanates in spray paint application. Use of Rast inhibition for diagnosis of sensitivity may indicate the precise sensitizing agent within a mixture.