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K O Ash

Publications and source records attributed to K O Ash.

At least 19 recordsLinked to original sources

Comparison of representative ranges based on U.S. patient population and literature reference intervals for urinary trace elements.

Reference intervals for trace elements are very hard to obtain because of the difficulty of defining a nonexposed reference population. However, representative ranges for trace elements obtained from a general patient population can provide useful information in interpreting laboratory results. We have used urine specimens submitted for trace metal analysis from patients residing in the United States to calculate representative ranges for 25 urinary trace elements, and to compare them to reference values taken from the literature. All urine analytes were measured by inductively-coupled plasma-mass spectrometry except chromium, which was measured by graphite furnace atomic absorption spectroscopy. For representative range calculation two approaches were used. In the non-parametric calculation first, the top 10% of results were discarded assuming that those specimens came from individuals with unusually high trace element exposures. Next the central 95% of the remaining data was taken as the reference interval. In the parametric calculation the specimens from exposed or not healthy individuals were assumed to appear as outliers and were discarded. The mean and S.D. were calculated, and used to determine representative ranges. The two approaches yielded very similar results, and worked remarkably well for 14 analytes. There were minor discrepancies for 7 analytes, and major for 4 analytes. All analyses of urinary trace elements included a urine creatinine value, which was used to express urinary trace element concentrations in terms of creatinine ratio. This corrects for differences in urine concentration that affects the results for random specimens.

Aging↗

Minimizing interferences in the quantitative multielement analysis of trace elements in biological fluids by inductively coupled plasma mass spectrometry.

The determination of trace and ultratrace elements in biological fluids, including urine and serum, by inductively coupled plasma mass spectrometry (ICP-MS) is discussed. Nonspectral interferences and their corrections by external calibration and calibrator addition are discussed in detail. External calibration with internal calibration and dilution is mostly sufficient to correct for encountered biological matrix effects. For some elements, such as Cs and Zn, the use of calibrator addition provides more accurate results. The importance of spectral interferences and their elimination by isotope selection was also studied. Two examples, Cu and Zn, demonstrate the prime importance of selecting an isotope with minimal polyatomic interferences for analysis. By using 65Cu and 68Zn, accurate results for urine and serum can be obtained without excessive pretreatment of samples. Two reference materials, Bio-Rad Lyphochek urine and Kaulson Contox sera, were analyzed. Accuracy was evaluated by comparison with target values, and precision was estimated by the CV within 95% confidence.

Calibration↗

Impact of cost cutting on laboratories: new business strategies for laboratories.

Cost reduction is the primary force driving healthcare reform. To survive and thrive in these tumultuous times, laboratories must adapt and implement new business strategies. Business paradigm shifts create opportunities for organizations with a plan; a wait-and-see attitude forecasts failure. Drawing upon an 11-year experience with the "ARUP business model," this work will highlight business strategies that have contributed to the success of this university-based reference laboratory. In the future, successful laboratories will implement new business strategies to become more effective members of the emerging integrated healthcare delivery teams. Within the laboratory, traditional organizational disciplinary boundaries, i.e., chemistry, microbiology, and hematology, are melding together to increase efficiency. Laboratorians must become influential members of institutional healthcare delivery teams formed to control utilization. Laboratory services are being adjusted to optimize patient care. Incremental pricing is only one of the strategies to be implemented to expand outpatient business to those in the region. Expanded computer capabilities, client services, specimen handling, marketing, and sales are also required. On a regional basis, service laboratories are increasingly joining forces to increase efficiency while at the same time improving the quality of patient care.

Chemistry, Clinical↗

Pharmacokinetics and results of dose escalation in cis-platin hyperthermic isolation limb perfusion.

BACKGROUND: We analyzed prospectively collected data on 145 cis-platin hyperthermic isolation limb perfusion (HILPs) for melanoma and soft-tissue sarcoma to determine the pharmacokinetics and maximum tolerable dose of cis-platin. There were 70 melanoma and 75 sarcoma patients. Dosages ranged from 26 to 265 mg/m2. Perfusate and systemic cis-platin levels were measured in patients perfused at doses of 190-200 mg/m2. Tissue levels were measured in patients perfused at 123-209 mg/m2. METHODS: Cis-platin HILP was well tolerated up to doses of 250 mg/m2 for lower extremities. Higher doses produced toxicities of rhabdomyolysis, myoglobinuria, hyponatremia, and neuropathy. Systemic levels of cis-platin were equivalent to those of routine intravenous administration, while perfusate levels were 33 times higher. Tissue levels of cis-platin were five to six times higher than effective intravenous levels. RESULTS: Six melanoma patients have developed local recurrences. All were perfused at doses < 120 mg/m2. However, regional nodal recurrences have occurred in six other patients perfused at doses < or = 200 mg/m2. Four sarcomas have recurred locally, but three of them were present at the time of perfusion. CONCLUSIONS: We conclude that 250 mg/m2 is the maximum tolerable dose of cis-platin for lower-extremity HILPs. Neoadjuvant cis-platin HILP may improve local control rates for sarcomas. However, no tolerable dose of cis-platin provides control of nodal metastases from melanoma.

Adult↗

A simple ICP-MS procedure for the determination of total mercury in whole blood and urine.

A simple and sensitive procedure for total mercury in whole blood and urine using inductively coupled plasma-mass spectrometry (ICP-MS) is described. Specimens are prepared by precipitation-extraction with 50% v/v hydrochloric acid containing EDTA and cysteine, centrifuged, and filtered through fritended screening column; the filtrates are directly analyzed by ICP-MS. The method is linear between 2 and 200 micrograms/L in the specimen with an absolute sensitivity of 0.2 microgram/L in the final supernatant. The assay variability at various concentrations (microgram/L) of mercury are as follows: intra-assay whole blood (n = 20)-4.6 +/- 0.6 (c.v. 12.3%), 18.3 +/- 1.1 (c.v. 6.1%), 56.4 +/- 2.8 (c.v. 5.0%); inter-assay whole blood (n = 15)-5.7 +/- 1.0 (c.v. 16.8%), 19.7 +/- 2.7 (c.v. 13.5%), and 50.1 +/- 6.9 (c.v. 13.7%); urine (n = 20)-9.3 +/- 1.2 (c.v. 12.9%), 29.6 +/- 2.2 (c.v. 7.4%). Recovery of organic and inorganic mercury from blood samples ranges from 91.6% to 110.2%. The method is suitable for analysis of total mercury, both organic and inorganic, in whole blood and urine.

Argon↗

Using 16O35Cl to correct for chloride interference improves accuracy of urine arsenic determinations by inductively coupled plasma mass spectrometry.

We have observed inaccurate urine arsenic values with the method of isobaric fractionation, which was designed to correct for the 40Ar35Cl interference with 75As quantitation by inductively coupled plasma mass spectrometry. Isobaric fractionation, which is based on ion intensities at m/z 77 and 82, consistently underestimates the 40Ar35Cl interference and overestimates urine arsenic. We present an improved method for identifying the argon-chloride interference. We observed that signal intensities for the species 16O35Cl and 40Ar35Cl are proportional (I75 = 0.0295 x I51 - 14.7, r2 = 0.998; where Ix is the normalized ion intensity at m/z X) in water and urine, over a broad range of chloride concentrations (0-800 mmol/L). The proportionality constant is remarkably stable within a run (mean and SD, 0.0295 +/- 0.0023, based on 10 replicates of five chloride calibrators, 0, 100, 200, 400, and 800 mmol/L). Increased sensitivity (50-fold) for detecting the 40Ar35Cl interference provides improved accuracy for urine arsenic quantitation as demonstrated by a split-sample comparison with graphite-furnace atomic absorption spectrophotometry.

Arsenic↗

Changes in sodium-lithium countertransport correlate with changes in triglyceride levels and body mass index over 2 1/2 years of follow-up in Utah.

We have previously reported from a cross-sectional study that plasma total cholesterol, triglycerides, and HDL-C were significantly and independently correlated with Na(+)-Li+ countertransport. These original participants were rescreened 2 1/2 years later (range of 20-58 months), with lipid, blood pressure, and Na(+)-Li+ countertransport measurements from both visits on 906 normotensive adults. The correlation found between age- and sex-adjusted triglyceride levels and Na(+)-Li+ countertransport at visit 1 (r = 0.34, p less than 0.0001) was reconfirmed at visit 2 (r = 0.32, p less than 0.0001). The Na(+)-Li+ countertransport correlations with HDL-C (r = -0.11, p less than 0.01) and body mass index (r = 0.24, p less than 0.0001) also remained at visit 2. After 30 months, there were significant increases of triglyceride, body mass index, blood pressure, and Na(+)-Li+ countertransport levels, and significant decreases of HDL-C and total cholesterol levels, after adjusting the changes in these variables between visit 2 and visit 1 for age, sex, time between the two visits, and the visit 1 level of the variable. Increases in triglycerides, cholesterol, and body mass index were significantly correlated with increases in Na(+)-Li+ countertransport (r = 0.23, r = 0.19, and r = 0.21, respectively). The correlations of the lipid and lipoprotein changes with Na(+)-Li+ countertransport changes were independent of body mass index and blood pressure changes. We conclude that increasing plasma triglyceride levels and body mass index are associated with increasing Na(+)-Li+ countertransport levels in both cross-sectional and longitudinal data.

Adolescent↗

Population-based frequency of dyslipidemia syndromes in coronary-prone families in Utah.

The frequency of familial dyslipidemia syndromes was determined from blood tests in 33 objectively ascertained families with early coronary heart disease (CHD) (two or more siblings with CHD by the age of 55 years). Three fourths of persons with early CHD in these families had 90th percentile lipid abnormalities (cholesterol level at or above the 90th percentile, triglyceride level at or above the 90th percentile, and/or high-density lipoprotein cholesterol (HDL-C) level at or less than the 10th percentile). The HDL-C and triglyceride abnormalities were twice as common as low-density lipoprotein-cholesterol abnormalities. The most common syndromes found were familial combined hyperlipidemia (36% to 48% of families with CHD), familial dyslipidemic hypertension (21% to 54% of families with CHD), and isolated low levels of HDL-C (15%), with overlapping familial dyslipidemic hypertension with familial combined hyperlipidemia and low-level HDL-C. Well-defined monogenic syndromes were uncommon: familial hypercholesterolemia being 3% and familial type III hyperlipidemia, 3%. Another 15% of families with CHD had no lipid abnormalities at the 90th percentile. Physicians should learn to recognize and treat these common familial syndromes before the onset of CHD by evaluating family history and all three standard blood lipid determinations. Failure to recognize and treat them leaves affected family members at high risk of premature CHD.

Cholesterol, HDL↗

Predictive value of a short dietary questionnaire for changes in serum lipids in high-risk Utah families.

Dietary questionnaires and serum cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol determinations were completed for 1239 subjects aged greater than or equal to 20 at each of two separate screenings. The mean time between screenings was 2.5 y. After correcting for potential confounding variables, reduction of a measure of dietary cholesterol and saturated fatty acids assessed by two simple questions was a significant independent predictor of reduction in total cholesterol in serum (p less than 0.005). Initial body mass index (BMI) and change in BMI were highly significant predictors of initial values and changes in total cholesterol, triglycerides, and HDL cholesterol in serum. Reduction of dietary saturated fatty acid and cholesterol was significantly correlated with initial serum cholesterol levels, which suggest that serum cholesterol screening may be an important motivating factor for dietary change. Important public health and research implications of these findings are discussed.

Adult↗

A gene for high urinary kallikrein may protect against hypertension in Utah kindreds.

The inheritance of 12-hour overnight total urinary kallikrein excretion and its association with family history of essential hypertension were studied in 405 normotensive adults and 391 youths in 57 Utah pedigrees. Total urinary kallikrein excretion was highly familial with 51% of the total variance attributable to a dominant allele for high total urinary kallikrein excretion and 27% attributable to the combined effects of polygenes and shared family environment. An estimated 28% of the population has one or two copies of the dominant allele for high total urinary kallikrein excretion (2.3 SD units higher than the low homozygotes). About 83% of the population could be assigned to one of the two genotypic populations. Individuals with the high total urinary kallikrein excretion genotype were significantly less likely to have one or two hypertensive parents (relative odds = 0.56, p = 0.042). We conclude that a dominant allele expressed as high total urinary kallikrein excretion may be associated with decreased risk of essential hypertension. Further studies should be performed to confirm this finding and to test for interactions between this apparently protective gene and other genetic and environmental determinants of essential hypertension.

Adolescent↗

Mechanism of false-negative urine cannabinoid immunoassay screens by Visine eyedrops.

To drug-free urine specimens, we added the following drugs of abuse to give concentrations twice the cutoff value for positive test results: 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (9-carboxy-THC), oxazepam, secobarbital, morphine, benzoylecgonine, amphetamine, or phencyclidine (PCP). Visine was then added. Although measured concentrations of several drugs were decreased in the presence of Visine, false-negative results were obtained only for 9-carboxy-THC for the EMIT-d.a.u. and TDx urine cannabinoid assays. Visine also decreased 9-carboxy-THC as measured by the Abuscreen assay. At low concentrations of Visine, false-negative cannabinoid results were attributable to the benzalkonium chloride ingredient of Visine. The added Visine was not detectable by routine urine analysis and had no effect on the activity of the glucose-6-phosphate dehydrogenase-drug conjugate used in the EMIT-d.a.u. assays. Moreover, analysis by gas chromatography/mass spectrometry showed no chemical modification or loss of 9-carboxy-THC in the Visine-adulterated urine specimens. However, Visine did increase the adhesion of 9-carboxy-THC to the borosilicate glass specimen containers. Results of ultrafiltration studies with Visine suggest that 9-carboxy-THC partitions between the aqueous solvent and the hydrophobic interior of benzalkonium chloride micelles, thereby reducing the availability of 9-carboxy-THC in antibody-based assays.

Amphetamine↗

Family history as an independent risk factor for incident coronary artery disease in a high-risk cohort in Utah.

To test independence of family history of coronary artery disease (CAD) as a risk factor for the development of new clinical CAD, data collected at 2 clinic visits on 1,196 men and women, ages greater than 20 years, were analyzed using Cox proportional hazard method. During a mean follow-up of 2.5 years, 16 new CAD cases were observed. After adjustment for age, sex, total cholesterol, high density lipoprotein cholesterol, hypertension, diabetes, cigarette smoking and body mass index, family history remained a highly significant predictor of future CAD (p = 0.0017). Only age was a more significant covariate (p = 0.0001) than family history. Sex (p = 0.00074) and serum total cholesterol (p = 0.015) also contributed significantly to CAD incidence while high density lipoprotein cholesterol, hypertension, diabetes, body mass index and several interaction terms did not improve the prediction in this population. These results provide evidence for the existence of other heritable risk factors which appear to contribute strongly to the occurrence of early CAD in many high-risk families.

Adult↗

Adulterants causing false negatives in illicit drug testing.

Illicit-drug users may attempt to falsify results by in vitro adulteration of specimens. We investigated eight additives (NaCl, Visine, handsoap, Drano, bleach, vinegar, golden-seal tea, and lemon juice) claimed by drug users to invalidate enzyme immunoassay (EIA) drug assays. We also analyzed adulterated urine specimens to determine if they could be identified, adding adulterants at several concentrations to 222 EIA-positive specimens confirmed by gas chromatography and mass spectrometry (GC/MS) to contain illicit drugs. To identify adulterated urines, we monitored pH, relative density, and urine color and turbidity at adulterant concentrations that falsified EIA results. Specimens contaminated with NaCl had relative densities greater than 1.035. Liquid Drano, bleach, and vinegar shifted urine pH outside the physiological range. Golden-seal tea caused a dark appearance, and specimens containing liquid soap were unusually cloudy. Lemon juice had no effect on the assays. Visine was the only adulterant not detected. The adulterants interfered somewhat differently with each of the drug assays. EIA assays for illicit drugs can be invalidated by specimen adulteration producing false-negative results. Therefore, if urine drug testing is to be conducted, pH, relative density, and appearance should be assessed and suspect specimens should be rejected. Not all adulterants can be detected, so observed collection is strongly recommended.

Acetates↗