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Biomedical subjects

George S Cembrowski

Publications and source records attributed to George S Cembrowski.

9 recordsLinked to original sources

Effect of waist circumference on reference intervals of liver-related enzyme tests in apparently healthy adult Mexican Americans, black and white Americans.

BACKGROUND: We used a more comprehensible and more physiologically valid indicator of obesity-related liver disease, waist circumference (WC), rather than BMI to study the effect of obesity on liver enzymes, easily measurable surrogates of liver disease. METHODS: WC, liver enzymes and pertinent demographic data were abstracted from NHANES III. After exclusion criteria were applied, we stratified the populations by sex and ethnicity and graphed the percentage of elevated enzymes per WC interval. RESULTS: There was a significant relationship between enzyme activity and WC (p<0.001 for ALT, p<0.01 for ALP, p<0.01 for AST, p=0.02 for GGT and p<0.05 for LD), and the relationship was stronger in females (p<0.002) and Mexican Americans (p<0.001). The enzyme-WC relationship is much weaker in non-Hispanic black females and males. CONCLUSION: As increases in liver enzyme activity can indicate potentially reversible liver disease, our graphs should be used by physicians to motivate obese, apparently healthy Mexican American and non-Hispanic white patients with elevated liver enzymes to reduce their WC.

Adult↗

Performance characteristics of several rules for self-interpretation of proficiency testing data.

CONTEXT: Proficiency testing (PT) participants can interpret their results to detect errors even when their performance is acceptable according to the limits set by the PT provider. OBJECTIVE: To determine which rules for interpreting PT data provide optimal performance for PT with 5 samples per event. DESIGN: We used Monte Carlo computer simulation techniques to study the performance of several rules, relating their error detection capabilities to (1) the analytic quality of the method, (2) the probability of failing PT, and (3) the ratio of the peer group SD to the mean intralaboratory SD. Analytic quality is indicated by the ratio of the PT allowable error to the intralaboratory SD. Failure of PT was defined (Clinical Laboratory Improvement Amendments of 1988) as an event when 2 or more results out of 5 exceeded acceptable limits. We investigated rules with limits based on the SD index, the mean SD index, and percentages of allowable error. RESULTS: No single rule performs optimally across the range of method quality. CONCLUSIONS: We recommend further investigation when PT data cause rejection by any of the following 3 rules: any result exceeds 75% of allowable error, the difference between any 2 results exceeds 4 times the peer group SD, or the mean SD index of all 5 results exceeds 1.5. As method quality increases from marginal to high, false rejections range from 16% to nearly zero, and the probability of detecting a shift equal to 2 times the intralaboratory SD ranges from 94% to 69%.

Chemistry, Clinical↗

Between-method variation in human chorionic gonadotropin test results.

BACKGROUND: Results on sera and calibrators vary 1.4- to 2.3-fold among commercial human chorionic gonadotropin (hCG) assays. The relative contributions of calibrators, standards, hCG charge isoforms, and major structural variants to this variation have not been quantified. METHODS: Purified hCG was separated by isoelectric focusing into four fractions with pI ranges of 3-4, 4-5, 5-6, and 6-7. These four fractions together with pure hCG, hyperglycosylated hCG, hCG beta-subunit (hCGb), nicked hCG, and hCGb core fragment (hCGbcf) were tested in nine commonly used commercial serum assays for hCG. The compositions of pure hCG preparations, standards, and commercial hCG preparations were determined by immunoassay. RESULTS: The three pure hCG preparations and the four hCG charge isoforms each showed parallel responses in the nine commercial hCG assays. Although wide variations were found in the detection of hCG structural variants by the nine assays (range for hyperglycosylated hCG, 468-1544 IU/L; for hCGb, 3187-5535 IU/L; for nicked hCG, 2736-4240 IU/L; and for hCGbcf, <2-130 IU/L), this did not correlate with the between-method variation observed in results for the three pure hCG preparations. Commercial preparations of hCG and calibrators showed great variation in their content of hCG structural variants (from 34% to 100% intact hCG). CONCLUSIONS: Intermethod differences in hCG results were not explained by changes in responses attributable to hCG charge isoforms or to hCG structural variants, but wide variation was observed in concentrations of hCG structural variants in calibrators and in detection of these structural variants. Differences in assay specificity and in composition of the calibrators are the most likely sources of between-method variation.

Calibration↗

Measurement of inaccuracy and imprecision of HCG methods using dilutions of the WHO 4th IS-HCG standard and a pregnant patient's serum.

INTRODUCTION: Differences in human chorionic gonadotropin (hCG) results obtained by seven different methods were documented by analyzing dilutions of the WHO 4th International Standard (IS) and a pregnant patient's serum. MATERIALS AND METHODS: Biases of +30.9 to -37.5% and +36.8 to -36.1% from the target concentration were found for the WHO 4th IS and patient sample dilutions, respectively. RESULTS: Imprecision was calculated from replicate measurements of hCG on the different sample dilutions. Imprecision ranged from 1.0% to 18.9% and 1.1% to 5.3% for the WHO 4th IS and patient sample dilutions, respectively. Using a maximum allowable error of 12.5% for hCG measurements, we found that two instruments were so biased that their hCG measurements could not be interchanged with hCG values produced by any of the other systems. DISCUSSION: It is ideal to use only one hCG methodology for the serial monitoring of hCG; otherwise, hCG methods should be carefully chosen to minimize inter-method bias.

Bias↗

Complete blood count reference interval diagrams derived from NHANES III: stratification by age, sex, and race.

BACKGROUND: Comprehensive, up-to-date "health-associated" reference interval studies of North American populations are uncommon. The third US National Health and Nutrition Examination Survey (NHANES III) was concluded in 1994 and yielded important reference interval data. OBJECTIVE: To obtain health-associated Coulter counter reference interval data from NHANES III according to age, sex, and race. METHODS: Of the 29,314 civilian noninstitutionalized US citizens who participated in NHANES III, approximately 25,000 had a complete blood count, red cell distribution width (RDW), platelet count, and automated white blood cell (WBC) differential determined on a Coulter S-Plus Jr. To determine health-associated reference intervals, we used the following exclusion criteria: pregnancy, breast feeding, obesity (body mass index [BMI] >40 and >35 for females and males, respectively), diastolic blood pressure >100 mm Hg, any smoking, any drinking of alcohol, recent treatment for anemia, creatinine level >2.5 mg/dL, glucose level >126 mg/dL, excessive thinness (BMI <8), recent surgery or hospitalization, or having antibodies to hepatitis viruses A, B, or C. The Coulter counter data (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume (MCV), mean cell hemoglobin concentration (MCHC), MCH, WBC count, platelet count, granulocyte count, monocyte count, lymphocyte count, RDW, platelet distribution width, and mean platelet volume) were separated into 6 sex/racial categories (female non-Hispanic white, female non-Hispanic black, female Mexican American, male non-Hispanic white, male non-Hispanic black, and male Mexican American) and 9 age groupings (10-14, 14-18, 18-25, 25-35, 35-45, 45-55, 55-65, 65-75, and >75 years). RESULTS: There was a high exclusion rate; for example, of the 20,685 individuals with measured hemoglobin levels, 12,688 (61.3%) were excluded. Percentile estimates could be derived accurately for almost all of the female age/sex categories. A few of the male Mexican American and non-Hispanic black categories contained observations for ages 45 to 75 years. CONCLUSIONS: There are age-dependent trends for many of the tests, notably in RDW, MCMV, platelet count, and granulocyte and lymphocyte percentages. Sex-dependent changes involved hemoglobin values, and race-related trends centered around mononuclear and lymphocyte percentages, hematocrit, MCHC, MCH, and hemoglobin. This study reveals the potential for using data mining of large samples to yield potentially useful reference ranges.

Adolescent↗

Unique approach to derivation of random error in laboratory assays: application to glycohemoglobin testing demonstrates poor clinical performance for immunochemistry assay.

The measurement of glycohemoglobin is the best measure of mean glucose within a 3-4 month range. As it is used for patient education, counseling, feedback control, and ultimately for patient motivation, its measurement should be optimally accurate and precise. Duplicate hemoglobin A1c readings were used to determine physiological (changes over time between measurements) and analytic variation of two widely used laboratory assays: Bio-Rad Variant II's high-performance liquid chromatography (HPLC) system and Roche's immunoassay. The average variation of grouped duplicates was calculated and graphed against corresponding time intervals. Regression to the y-intercept (0 day separation between readings) was used to determine the analytic variation. Analytic coefficients of variation (CVs) for the HPLC and immunoassay were determined as 2.6% and 5.1%, respectively. The CV of the immunoassay method exceeds physiologically established limits of 2-3% and those of the National Glycohemoglobin Standardization Program (3-4%). The Bio-Rad HPLC system produces a CV within these limits.

Chromatography, High Pressure Liquid↗

Temporal approach to hematological test usage in a major teaching hospital.

In the era of slowly increasing laboratory budgets, identifying usage patterns can be an important first step in decreasing unnecessary laboratory testing. From January 1, 1998, through December 27, 2002, we studied inpatient laboratory utilization at the University of Alberta Hospital, a large Canadian teaching hospital (665 inpatient beds with an almost 100% continuous occupancy rate). The daily numbers of complete blood cell count (CBC), CBC with differential (CBCD), international normalized ratio, activated partial thromboplastin time, vitamin B12, and red cell folate (FOL) tests were correlated with regularly occurring hospital events, such as weekends, statutory holidays, and resident changeover dates. Testing for hematological monitoring (CBC, CBCD) at our institution has been increasing at an average of 2% to 6% per year with a recent (2001 onward) rate of increase in hematological diagnostic testing (vitamin B12 and FOL) of close to 10%. As expected, laboratory usage was statistically significantly higher on weekdays compared with weekends. During the weekdays, ordering frequencies on Monday and Friday were shown to be statistically significantly higher than on the other days. A nadir occurred on Thursday and on the weekend. This finding was postulated to be due to a combination of attending physician unfamiliarity and defensive testing. Resident changeovers did not contribute to an increase in Monday laboratory testing, as was initially thought, nor did holidays. We believe that we can use our findings to decrease laboratory use. First, weekend or midweek use might become the appropriate standard for frequency of testing. Second, we must alert attending physicians (and residents who are soon to be attending physicians) about their subliminal need to increase testing during changeovers.

Hematologic Tests↗

Performance of a revised cardiac troponin method that minimizes interferences from heterophilic antibodies.

BACKGROUND: Recent guidelines for use of cardiac troponin to detect cardiac damage and for cardiovascular risk stratification have made increasingly sensitive troponin assays important. Troponin assays continue to be plagued by interferences caused by heterophilic antibodies (HAs). We evaluated the performance of a revised cardiac troponin I (cTnI) assay designed to have increased analytical sensitivity and to minimize the effect of HAs. METHODS: The revised Dade Behring Dimension cTnI assay was evaluated according to NCCLS EP5-A at five institutions. Plasma samples from 14 309 patients were assayed by the original Dimension cTnI assay. To identify samples that may have interfering HAs, samples with values >1.4 microg/L were reanalyzed on the Dade Behring Stratus CS cTnI assay. Samples with possible interfering antibodies were also analyzed before and after selective absorbance studies on the revised Dade Behring Dimension cTnI assay. RESULTS: The limit of quantification in the revised method was 0.1 microg/L with imprecision (CV) of 11-17% at 0.1 microg/L. Values correlated well with the Stratus CS cTnI method: revised = 1.06(original) + 0.01; r = 0.98, S(y/x) = 0.25 microg/L). Falsely increased results consistent with myocardial infarction by the original Dimension cTnI assay and presumably attributable to HAs were identified in 0.17% of all patients with samples submitted for cTnI analysis. The revised Dimension cTnI assay eliminated the interference in 17 of 25 samples identified and greatly decreased the interference in the other 8. CONCLUSIONS: The revised Dimension cTnI method greatly minimizes the effect of interfering HAs. It also exhibits analytical performance characteristics consistent with recent guidelines for use of this assay to detect cardiac damage.

Adolescent↗