Clinical laboratory quality control: a costly process now out of control.

We studied laboratory internal quality control (QC) processes using the College of American Pathologists Q-Probes program. Over 500 institutions participated, providing practices based on approximately 710,000 cholesterol, 880,000 calcium, 400,000 digoxin, and 1,180,000 hemoglobin QC results. The costs of QC included participant median control samples rates comprising 9.1, 9.4, 37.0, and 6.8% for the four analytes respectively, repeat patient test rates of 0.36% for hemoglobin to 0.65% for digoxin, and median delays in reporting results when QC exceptions occurred of 15.8 min for calcium to 24.7 min for hemoglobin. Quality control practices were complex and highly variable among participants and frequently differed from internal laboratory protocols and from long-established quality guidelines. We conclude that QC is costly, and laboratorians frequently do not follow established QC practices, in part because they are complex. To improve compliance, we believe QC practices must be simplified.

Clinical chemistry education in the United States.

Entrance into a clinical chemistry career in the US can be obtained through a variety of avenues, ranging from very formal to no formal training requirements. A frequent starting point is through a formal medical technology program at the baccalaureate level. Nonphysicians, interested in an advanced career, have also the option to choose their point of entrance through a formal graduate or postdoctoral program. The main source for obtaining a Master of Science or Doctoral degree with a major in the clinical laboratory sciences, is through Departments of Pathology. Physicians desiring to subspecialize in clinical chemistry can obtain some of the training through a residency program in Pathology. Clinical chemistry is an essential component of both the clinical pathology (CP) residency and the combined residencies in anatomic and clinical pathology (AP/CP). In addition, fellowships in clinical chemistry are available for graduates with doctorate degrees in the chemical and biological sciences as well as for physicians with laboratory experience.

Lipase activity in serum measured with Ektachem is often increased in nonpancreatic disorders.

For patients with symptoms of pancreatitis, measurement of amylase in serum reportedly is more sensitive than that of lipase in acute pancreatitis, whereas lipase reportedly is more specific. However, serum lipase activities exceeding the upper reference limit (URL) have been reported for many patients who did not have pancreatitis. I reviewed the serum lipase and amylase concentrations of 493 consecutive inpatients and emergency department patients for whom both tests were ordered. Serum lipase and amylase activities, determined with an Ektachem 700 analyzer, were less than or equal to URL for 390 patients (83%) and greater than URL for 103. Medical records of 101 of these 103 were reviewed; 18 had acute or chronic relapsing pancreatitis. In this latter group, serum lipase values greater than URL had 100% sensitivity and 84% specificity; those of serum amylase greater than URL had 72% sensitivity and 88% specificity. However, the test combination of serum lipase greater than URL and serum amylase less than or equal to URL also occurred in 84% of the patients in which review of the medical records revealed nonpancreatic gastrointestinal or hepatobiliary disorders as the primary problem (n = 55). Therefore, serum lipase activity measured with the Ektachem assay is also often increased in patients with intra-abdominal disorders that appear to be nonpancreatic.

Increased transcapillary escape rate of albumin in nondiabetic men in response to hyperinsulinemia.

Diabetic patients manifest increased vascular permeability. To determine whether insulin per se might increase vascular permeability, five nondiabetic men were studied by the hyperinsulinemic-euglycemic clamp technique. Each subject received a 0.72-nmol/kg body wt i.v. insulin bolus, followed by a 72-pmol.kg-1.min-1 insulin infusion for 4 h. Euglycemia was maintained by the Biostator glucose controller. At 7 h of study, 10 microCi i.v. 125I-labeled albumin was injected as bolus dose. Frequent blood samples were drawn during the next 70 min for determination of the transcapillary escape rate (TER) of albumin. Subjects returned 1-2 wk later for a control study, during which 0.45% saline was infused at a rate identical to the dextrose and insulin infusion rates during the hyperinsulinemic clamp. The mean +/- SE serum insulin levels during the hyperinsulinemic clamp and saline infusion were 9786 +/- 126 and 46 +/- 4 pM, respectively, whereas serum glucose during the two sessions was similar (5.0 +/- 0.2 vs. 4.8 +/- 0.1 mM, NS). Identical fluid volumes were infused during the two sessions (1767 +/- 197 ml/7 h), and urine outputs did not differ significantly (1615 +/- 309 vs. 1035 +/- 248 ml/7 h). The TER of albumin was greater in all five men after hyperinsulinemia than after saline infusion (18.3 +/- 2.7 vs. -2.8 +/- 2.3%/h, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional interlaboratory standardization of determinations of cholesterol, high-density lipoprotein cholesterol, and triglycerides.

The Clinical Chemistry Forum of Central Virginia initiated a lipid standardization program to help ensure that its members meet the current National Cholesterol Education Program guidelines for cholesterol testing, and to standardize assays of high-density lipoprotein (HDL) cholesterol and triglycerides so as to provide accurate lipid profiles. We found that freshly collected, never-frozen human sera must be used to assess interlaboratory accuracy for cholesterol, HDL cholesterol, and triglycerides assays, and that at least 23 samples are required to detect a 3% bias with 90% power when the between-laboratory imprecision (CV) is 3%. After recalibration, all 12 laboratories had a mean HDL cholesterol bias less than or equal to 5%, nine of 10 laboratories had a mean HDL cholesterol bias less than or equal to 40 mg/L for samples with values less than or equal to 570 mg/L, and 10 of 12 laboratories had a mean triglycerides bias less than or equal to 10% for fresh human sera split between participants and the Centers for Disease Control. Pools of frozen human sera were shown to have matrix biases greater than 3% for cholesterol in seven of 11 laboratories, and greater than 40 mg/L for HDL cholesterol in six of nine laboratories.

Clinical utility of Ektachem-determined bilirubin fractions for classifying adult inpatients.

We determined total bilirubin, "direct" and "indirect" bilirubin fractions, and, in parallel, using Ektachem slides, the total, conjugated, unconjugated, and delta bilirubin contents for specimens from 88 adult inpatients at various times during hospitalization in a tertiary-care facility. We wanted to see if the results correlated with the patients' diagnoses, based on a review of medical records and other laboratory data. The patients (including some with mixed disease types) were assigned to one of three predominant disease-process groups: obstructive liver disease, parenchymal liver disease, or hemolytic disease. Ektachem bilirubin fractions and the comparable total, "direct," and "indirect" bilirubin fractions showed equal sensitivity in screening and monitoring disease in all three groups. Measurements of conjugated bilirubin, unconjugated bilirubin, and their sum were sufficient for evaluating bilirubin abnormalities in this complex patient population. Determining delta bilirubin with the total bilirubin slide was rarely useful clinically. Thus, laboratories using Ektachem instrumentation for bilirubin testing can routinely eliminate the extra costs and occasional problems associated with running both bilirubin slides, reserving delta bilirubin determinations for unusual cases.