Within- and between-subject variation in commonly measured anthropometric and biochemical variables.
BACKGROUND: The biological variation of some commonly assessed metabolic variables in healthy subjects has not been studied extensively. The aim of the study was to assess, in 12 healthy subjects (6 male and 6 female; mean (SD) age; 22.7 (1.5) years) following an overnight fast, the day-to-day variation of body fat (impedance method), triglycerides, nonesterified fatty acid (NEFAs), glycerol, 3-hydroxybutyrate (3-OHB), lactate, glucose, insulin (RIA), C-peptide, and glucagon on 12 consecutive days. METHODS: Between- and within-subject coefficients of variation (CVG and CVW) were estimated using a random effects analysis of variance, and assay variation was subtracted to give the coefficient of within-subject biological variation (CVI). Individuality indices were calculated as CVW/CVG. RESULTS: The overall means, CVI, and individuality indices were as follows: for body fat, 24.2%, 10%, and 0.3; for triglycerides, 0.61 mmol/L, 21%, and 1.1; for NEFAs, 376 micromol/L, 45%, and 1.4; for glycerol, 48 micromol/L, 36%, and 0.8; for 3-OHB, 43 micromol/L, 61%, and 1.5; for lactate, 0.88 mmol/L, 31%, and 1.1; for glucose, 4.9 mmol/L, 4.8%, and 0.7; for insulin, 52 pmol/L, 26%, and 1.0; for C-peptide, 0.39 nmol/L, 24%, and 0.9; and for glucagon, 53 ng/L, 19%, and 0.8. CONCLUSIONS: The data presented here are necessary for the evaluation of several important metabolic variables in individual and group studies. The biological variation of some metabolites makes it difficult to characterize the status of healthy subjects with a single measurement. (+info)
Affinity chromatography: a review of clinical applications.
Affinity chromatography is a type of liquid chromatography that makes use of biological-like interactions for the separation and specific analysis of sample components. This review describes the basic principles of affinity chromatography and examines its use in the testing of clinical samples, with an emphasis on HPLC-based methods. Some traditional applications of this approach include the use of boronate, lectin, protein A or protein G, and immunoaffinity supports for the direct quantification of solutes. Newer techniques that use antibody-based columns for on- or off-line sample extraction are examined in detail, as are methods that use affinity chromatography in combination with other analytical methods, such as reversed-phase liquid chromatography, gas chromatography, and capillary electrophoresis. Indirect analyte detection methods are also described in which immunoaffinity chromatography is used to perform flow-based immunoassays. Other applications that are reviewed include affinity-based chiral separations and the use of affinity chromatography for the study of drug or hormone interactions with binding proteins. Some areas of possible future developments are then considered, such as tandem affinity methods and the use of synthetic dyes, immobilized metal ions, molecular imprints, or aptamers as affinity ligands for clinical analytes. (+info)
History of clinical chemistry in a children's hospital (1914-1964).
The historical development of a charitable children's hospital and the evolution of its clinical laboratory are presented. With the appearance of practical quantitative blood chemistry tests in the period between the two World Wars, applications to pediatrics were hampered by the need for ultramicro procedures then unavailable and for improved skin-puncture blood sampling. World War II brought economic demands that forced the hospital to privatize its beds and to charge fee-for-services. In turn, this brought added income, allowing the hiring or subsidizing of a professional staff, including the clinical chemist. The development of ultramicro blood chemistry followed, along with improved skin-puncture technology. (+info)
A golden age of clinical chemistry: 1948-1960.
This segment of history aims to inform the new, and remind the not-so-new, members of the profession about the relatively recent period that initiated the dominant role played by technological innovation in the modern investigation of disease. The 12 years from 1948 to 1960 were notable for introduction of the Vacutainer tube, electrophoresis, radioimmunoassay, and the AutoAnalyzer. Also appearing during this interval were new organizations, publications, programs, and services that established a firm foundation for the professional status of clinical chemists. It was a golden age. (+info)
A reference method laboratory network for cholesterol: a model for standardization and improvement of clinical laboratory measurements.
BACKGROUND: Accurate and precise measurement of blood cholesterol plays a central role in the National Cholesterol Education Program's strategy to reduce the morbidity and mortality attributable to coronary heart disease. Matrix effects hamper the ability of manufacturers to adequately calibrate and validate traceability to the National Reference System for Cholesterol (NRS/CHOL). CDC created the Cholesterol Reference Method Laboratory Network (CRMLN) to improve cholesterol measurement by assisting manufacturers of in vitro diagnostic products with validation of the traceability of their assays to the NRS/CHOL. METHODS: CRMLN laboratories established the CDC cholesterol reference method (modification of the Abell-Levy-Brodie-Kendall chemical method) and are standardized using CDC frozen serum reference materials. CRMLN laboratories use common quality-control materials and participate in monthly external performance evaluations conducted by CDC. The CRMLN performance criteria require member laboratories to agree with CDC within +/-1.0% and maintain a CV < or =2.0%. RESULTS: From 1995 to 200 the CRMLN laboratories met the accuracy criterion 97% of the time and the precision criterion 99% of the time. During this time period, the CRMLN maintained an average bias to CDC of 0.01% and an average collective CV of 0.33%. CONCLUSIONS: CDC established the CRMLN as the first international reference method laboratory network. The CRMLN assists manufacturers in the validation of the calibration of their diagnostic products so that clinical laboratories can measure blood cholesterol more reliably. The CRMLN can serve as a model for other clinical analytes where traceability to a hierarchy of methods is needed and matrix effects of the field methods with processed calibrators or reference materials are present. (+info)
Establishment and characteristics of four sub-strains of F344 rats reared on various low protein and low energy diets.
Four sub-strains, reared by sib-mating and having for their origin the F344/DuCrj strain of rats, were established by feeding with different levels of low protein and low energy diets, and their characteristics investigated. The amounts of crude protein (CP) and digestible energy (DE) in the four diets were 17.6%-3.0 kcal, 10.5%-2.5 kcal, 8.4%-2.0 kcal, and 10.5%-2.5 kcal, respectively, and the four sub-strains established here were provisionally designated as F344/Tig1, F344/Tig2, F344/Tig3 and F344/Tig4, respectively. Intakes of nitrogen-corrected metabolizable energy (MEn) did not differ, and a large intake of digestible crude protein (DCP) was observed in F344/Tig1 rats. The body weight of rats provided with lower-nutrient diets showed a tendency to decrease until the F2 generation, but no change among the generations was seen subsequently, and the same compiled differences in protein content were maintained. Similar transitions were observed in the lifetime rearing test. Though F344/Tig3 rats, which were reared on minimum nutrients, showed a tendency to delayed puberty, we were easily able to breed four pairs in every generation using procedures similar to those used for other strains of rats. There were no differences among the F344/Tig1 to -3 strains of rats in body length, digestive tract length, or organ weight per body weight, and all the rats had a normal range of biochemical values. But the F344/Tig4 showed a high glutamic-oxaloacetic transaminase (GOT), and a tendency to decreased liver function and a shorter lifespan. These sub-strains of F344 rats clarified differences in fatty acid compositions, such as docosahexaenoic acid (DHA) in serum, liver and the brain. The rats were intended to be useful animal models for the study of nutritional environments and their influence on the memory and learning. (+info)
Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting.
To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P < 0.001), and the levels of counterregulatory factors increased during the fast [P < 0.05; glucagon and free fatty acids (FFA) with a linear increase and epinephrine, norepinephrine, and cortisol with a clear underlying circadian rhythm]. Growth hormone secretion increased from the first to third day of fasting (P < 0.05) but actually decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P < 0.05), whereas no effect of gender on beta-cell polypeptides was observed. A high body mass index resulted in higher insulin and C-peptide levels during the fast (P < 0.05). In conclusion, we have provided reference intervals for glucoregulatory factors during a 72-h fast. We observed a diminished beta-cell response concomitant with an increased secretion of counterregulatory hormones. These results should be of clinical and scientific value in the investigation of hypoglycemic disorders. (+info)
Toxicology and carcinogenesis studies of p,p'-dichlorodiphenyl sulfone in rats and mice.
p,p'-Dichlorodiphenyl sulfone (DDS) is used as a starting material in the production of polysulfones and polyethersufones, a family of thermoplastics. DDS was studied because of its high production volume and use. In toxicology studies, 10 Fischer 344 rats and 10 B6C3F1 mice/sex/group were fed diets containing 0, 30, 100, 300, 1,000 or 3,000 ppm DDS for 14 weeks. All animals survived until the end of the studies. Mean body weights of groups exposed to 300 ppm or greater were significantly decreased. Liver and kidney in rats and liver in mice were the major target organs of DDS toxicity. Dose-related increases in liver weights and incidences of centrilobular hepatocyte hypertrophy were observed in DDS-exposed groups. Nephropathy was seen in male and female rats only at and above 300 ppm. Neurotoxicity evaluations were negative in DDS-treated animals. Clinical chemistry and hematology parameters were minimally affected. In the 2-year toxicity and carcinogenicity studies, 50 rats and 50 mice/sex/group were fed diets containing 0, 10 (male rats), 30, 100, or 300 ppm DDS for 104 to 105 weeks. Survival of exposed groups was not affected. There were no clinical signs of toxicity related to DDS exposure. Final mean body weights were 2-17% lower in DDS-treated groups. Liver was the only target organ of DDS-induced toxicity. The incidence of centrilobular hepatocyte hypertrophy in mice and rats, and the incidence of bile duct hyperplasia and centrilobular degeneration in female rats was significantly greater than in controls. A no-observed-adverse-effect level (NOAEL) of 30 ppm DDS in the diet (1.5 mg/kg body weight) was established for rats. DDS was not carcinogenic in these studies. (+info)