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Biomedical subjects

H K Naito

Publications and source records attributed to H K Naito.

At least 19 recordsLinked to original sources

Accurate measurement of serum total cholesterol: the need for standardization.

Heightened awareness of the importance of cholesterol and heart disease has increased cholesterol testing in the United States. The demand for reliable cholesterol measurements has become a focal concern of the patient as well as the clinician. This paper covers the major analytical and preanalytical issues and factors that can affect the reliability of cholesterol results. We discuss factors that lead to impression and inaccuracy; solutions for some of the major problems; resources and techniques to help standardize cholesterol measurement; and preanalytical issues that can affect cholesterol results--i.e., patient preparation; collection, processing, storage and proper analysis of the specimen; biological and seasonal variations; age and gender; diet; alcohol consumption; weight changes; exercise; primary diseases; and infections and trauma. Many of these can be controlled by the physician, resulting in more reliable cholesterol readings under stable metabolic conditions. Accurate values will help to classify the patient's coronary heart disease risk, define appropriate treatment strategies, and simplify monitoring of dietary and/or drug intervention.

Blood Chemical Analysis

Interlaboratory comparison of glycohemoglobin results: College of American Pathologists Survey data.

We describe recent changes in the College of American Pathologists Glycohemoglobin (gHb) Survey, made to improve the assessment of interlaboratory variability and the accuracy of results reported. The questionnaire portion of the survey was revised to include an updated list of current methods, and results for survey specimens were grouped according to the component measured (Hb A1, Hb A1c, or total gHb). The survey specimen material was changed to a material thought to give more reliable results with all available methods. After these changes, instituted in 1989, between-laboratory CVs decreased for some methods. Furthermore, gHb values between method types were more consistent with results obtained from fresh blood samples under very controlled laboratory conditions. However, these recent data also show that the interlaboratory variability is still quite high for some methods and that the variability within and between method types is still very great. We describe a pilot standardization program for gHb measurement.

Chromatography, Affinity

Progress in lipid reporting practices and reliability of blood cholesterol measurement in clinical laboratories in Nebraska. Efforts to align results with the Centers for Disease Control, and feasibility of meeting National Cholesterol Education Program Guidelines.

The National Cholesterol Education Program has recommended that all laboratories be consistent, precise, and accurate in the reporting and measurement of blood cholesterol levels. In a follow-up to a 1984 survey study, we assessed the changes in reporting procedures for measurements of blood lipid levels in 16 clinical laboratories in Nebraska. Using human serum reference materials of known cholesterol concentrations provided by the Centers for Disease Control, we also assessed the precision and accuracy of measurement of blood cholesterol levels in clinical laboratories in Nebraska. Fourteen of the 16 laboratories restudied in 1987 had altered the reference range for total serum cholesterol since 1984, 86% of whom lowered the upper limit of the reference range. Eleven of 16 laboratories expressed reference ranges for total serum cholesterol in terms of patient age in 1987, while only 7 of 20 did in 1984. Gender-based reference ranges increased from 0 to 5 from 1984 to 1987. Similar trends were seen in the reporting of high-density lipoprotein cholesterol and triglyceride concentrations. Reporting procedures varied greatly; only 1 laboratory used National Cholesterol Education Program risk levels for measuring total serum cholesterol levels. Fifteen laboratories met the National Cholesterol Education Program recommendation for precision (coefficient of variation, less than or equal to 5%) and 78% of laboratories obtained results that satisfied the current recommendation for accuracy (within 5% of "true value," as determined by the Centers for Disease Control).

Adult

Dietary influences on cardiovascular disease risk in anabolic steroid-using and nonusing bodybuilders.

Recent studies have described an association between high-risk lipoprotein profiles and anabolic steroid abuse by athletes. However, none have included a comprehensive evaluation of diet as a confounding variable. The risk of cardiovascular disease (CVD) and its associations with drug abuse, dietary patterns, and training regimens were evaluated in 18 steroid-using (SU) and 17 non-steroid-using (NSU; no history of drug use or greater than or equal to 1 year drug-free) male bodybuilders. CVD risk was also evaluated in 10 control males. Fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and HDL subfractions 2 and 3, low-density (LDL) and very-low-density (VLDL) lipoprotein cholesterol, apoproteins (APO) A-1 and B, and triglycerides (TG) were analyzed at baseline (greater than or equal to 6 months drug-free) and the peak of steroid self-administration in SU. NSU were tested at similar times. Baseline CVD risk factor ratios (TC/HDL) were elevated (greater than 4.97) in 44% of SU and 24% of NSU. When baseline LDL and HDL values were compared to National Cholesterol Education Program CVD risk guidelines, these percentages stayed the same. At the peak of steroid administration significant changes were observed in LDL (22% increase), HDL (63% decrease), HDL-2 (86% decrease), HDL-3 (54% decrease), and TC/HDL (85% increase). No similar measures were observed among NSU or controls. Diets of all bodybuilders were similar, and included a daily intake of 5739 (+/- 2500) kcal, 324 (+/- 163) g protein, 637 (+/- 259) g carbohydrate, 214 (+/- 109) g fat, 5 (+/- 8) g alcohol, 1413 (+/- 1151) mg cholesterol, and a P/S ratio of 0.6 (+/- 0.3). Significant relationships between dietary fats and serum lipids were observed in the NSU. Polyunsaturated fatty acids were correlated with TG and VLDL (r = 0.69; p = 0.01), and TC/HDL (r = 0.06; p = 0.04). Total fats were correlated with TG (r = 0.57; p = 0.05), HDL-3 (r = -0.62; p = 0.04), and VLDL (r = 0.57; p = 0.05), and saturated fats with HDL-3 (r = -0.59; p = 0.055). Diet was moderately associated with lipoproteins in SU, but steroids had a much greater influence on CVD risk. Despite disease promoting diets NSU had relatively average CVD risk that may be attributed to protective effects of rigorous training.

Adolescent

The need for accurate total cholesterol measurement. Recommended analytical goals, current state of reliability, and guidelines for better determinations.

We have approached a dawn of a new era in detection, evaluation, treatment, and monitoring of individuals with elevated blood cholesterol levels who are at increased risk for CHD. The NHLBI's National Cholesterol Education Program will be the major force underlying this national awareness program, which is dependent on the clinical laboratories providing reliable data. Precision or reproducibility of results is not a problem for most of the laboratories, but accuracy is a major concern. Both the manufacturers and laboratorians need to standardize the measurement for cholesterol so that the accuracy base is traceable to the NCCLS NRS/CHOL. The manufacturers need to adopt a uniform policy that will ensure that the values assigned to calibration, quality control, and quality assurance or survey materials are accurate and traceable to the NCCLS/CHOL. Since, at present, there are some limitations of these materials caused by matrix effects, laboratories are encouraged to use the CDC-NHLBI National Reference Laboratory Network to evaluate and monitor their ability to measure patient blood cholesterol levels accurately. Major areas of analytical problems are identified and general, as well as specific, recommendations are provided to help ensure reliable measurement of cholesterol in patient specimens.

Cholesterol

Secondary hypertriglyceridemia and hyperlipoproteinemia in patients with primary asymptomatic gout.

We carefully selected 30 men with primary gout, rendered asymptomatic by therapy, to examine the frequency and type of hyperlipidemia and hyperlipoproteinemia, with the objective of determining whether serum uric acid, alcohol intake, liver function, kidney function, and (or) drugs were participating in the secondary lipid disorder. Sixty-one age- and sex-matched men were used as controls. About 73% of the gout patients had hypertriglyceridemia, 1.6-fold the frequency found in the control group. Types IV and IIb lipoprotein electrophoretic patterns were most prevalent in the gout group. Neither alcohol intake nor hyperuricemia, per se, seems to be the cause of the lipid and lipoprotein disorder and cannot be related to liver or kidney dysfunctions. Obesity was the major underlying factor associated with the lipidemia. The study suggests that diet and, possibly, defective clearance of triglycerides may be etiologic factors associated with the abnormal serum triacylglycerol (triglyceride) and lipoprotein concentrations in these individuals.

Blood Chemical Analysis

Dietary induced atherogenesis in swine. Morphology of the intima in prelesion stages.

Hypercholesterolemia was induced in pigs by feeding a chow diet supplemented with 1.5% cholesterol and 19.5% lard for periods up to 12 weeks. The aortic intima from areas of spontaneously differing permeability to proteins, as demarcated by their uptake of Evans blue dye, was examined using light microscopy and both scanning and transmission electron microscopy to describe the earliest detectable changes in intimal morphology induced by the diet. After 2, 4, and 6 weeks of feeding, cholesterol/lardfed pigs demonstrated monocyte adherence to the endothelium in areas of enhanced permeability (blue areas) in 86% of samples examined, as compared to 52% in areas of lesser permeability (white areas) and 17% in control animals. Similarly, the number of monocytes in the intima was higher in blue areas than in adjacent white areas or blue areas from control animals. After 12 weeks of feeding, all blue areas showed intimal monocytes, with fewer seen in white areas. Aortic endothelial cells in hypercholesterolemic pigs were normal in ultrastructural appearance, except they contained more lysosomes and cytoplasmic filaments than those from control animals. No lesions were observed at 2, 4, and 6 weeks, although plasma cholesterol levels were substantially elevated (200-400 mg/dl) at these times. A marked hyper-beta-lipoproteinemia was evident from 4 weeks onward, but no elevation of serum triglycerides was evident at any stage. Plasma phospholipid concentrations increased but not in direct proportion to cholesterol levels. At 12 weeks, foam cell lesions were observed in areas of enhanced permeability but not in adjacent areas of normal permeability. Lesion foam cells appeared to be derived from the monocytes which adhered to and penetrated the endothelium at earlier stages, since no intimal involvement, or lipid engorgement, by medial smooth muscle cells was observed.

Animals

Determination of urinary thiamine by high-pressure liquid chromatography utilizing the thiochrome fluorscent method.

A sensitive, reproducible, and specific method for the determination of urinary thiamine has been established. Unique to the use of high-pressure liquid chromatography (HPLC) to separate the fluorescent thiamine derivative from interfering fluorescent compounds. Urine samples were passed through a Decalso catoin-exchange column, washed with 0.5 M KCl to remove some interfering compounds, and eluted with 3.4 M KCl. The eluted thiamine was converted to the fluorescent derivative, thiochrome, by reaction with alkaline potassium ferricyanide. The reaction mixture was extracted with isobutanol and subjected to HPLC monitored by a fluorescent detector. Within-day and day-to-day coefficients of variation proved to be 2.5% and 1.2% respectively. Recovery of added thiamine (range 0.04 to 2.0 microgram/ml) averaged 99.9 +/- 5.3%. The sensitivity of this method was 0.03 microgram/ml.

Animals

Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys.

A semipurified diet containing 1.2 mg of cholesterol/Cal was fed to cynomolgus monkeys (Macaca fascicularis). At the end of 6 months, a group of 18 animals was killed for evaluation of atherosclerosis in the aorta and the coronary arteries. The remaining monkeys were assigned to three groups of 18 animals each and fed, during the following 18 months, semipurified diets containing 0.34 mg of cholesterol/Cal with or without alfalfa meal, or a diet consisting entirely of Monkey Chow. a decrease in cholesterolemia and plasma phospholipid levels, normalization in the distribution of plasma lipoproteins, and reduction in the extent of aortic and coronary atherosclerosis were observed in monkeys fed the semipurified diet containing alfalfa, although the intake of cholesterol remained as high as in the usual American diet. These changes, also observed in monkeys fed a chow diet almost devoid of cholesterol, suggest that alfalfa counteracts the atherogenic effect of dietary cholesterol.

Animals

Treatment of established atherosclerosis during cholesterol feeding in monkeys.

A semipurified diet containing 43% of the calories as fat and 1.2 mg of cholesterol/cal was fed to cynomolgus monkeys (Macaca fascicularis) for 6 months; the cholesterol content was reduced to 0.34 mg/cal for the next 18 months. During the latter period, the monkeys were assigned to 4 groups of 18 animals each and received the following dietary additions: A, none (controls); B, cholestyramine (5%, w/w); C, dextrothyroxine (0.003%); and D, Wy-14,643 (0.45%). Cholestyramine normalized plasma lipid levels and reduced the size of aortic and coronary atherosclerotic lesions in spite of the high-fat, high-cholesterol intake. Dextrothyroxine reduced cholesterolemia but did not modify the extent of arterial lesions. Wy-14,643 changed neither plasma cholesterol levels nor the extent of atherosclerosis.

Acetates

Studies on a beta-migrating high density lipoprotein.

An unusual serum lipoprotein (Lp) profile was detected in a Japanese family. A double beta-Lp was observed when serum was subjected to polyacrylamide gel electrophoresis. The slower migrating beta-Lp was identified as a subfraction of high density lipoprotein (HDL). It was present in the d 1.063--1.21 fraction, migrated to the position designated as the midband L.1 (sinking pre-beta-lipoprotein) by Mead, M.G. and Dangerfield, W.G. (1974) (Clin. Chim. Acta 51, 173--182) [1], and reacted against human anti-beta-Lp antiserum. This lipoprotein contained greater amounts of triglyceride than the usual beta-lipoprotein and could not be clearly detected by paper electrophoresis. Individuals exhibiting this high density midband lipoprotein appeared to be heterozygous for an autosomal dominant gene. Although other reports have indicated the possibility of a positive association between the occurrence of serum lipoproteins with unusual eletrophoretic mobility and premature ischemic heart disease, no such correlation was demonstrable in these subjects.

Adolescent