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Biomedical subjects

S C Kazmierczak

Publications and source records attributed to S C Kazmierczak.

At least 19 recordsLinked to original sources

Transient nature of interference effects from heterophile antibodies: examples of interference with cardiac marker measurements.

Two-site immunoassay methods have become the standard technique for measurement of a wide variety of drugs, hormones, and cell proteins. One limitation of these methods is their susceptibility to interference from heterophilic antibodies present in the sera of some patients. Human anti-murine antibodies represent a common heterophile antibody that can bind to mouse immunoglobulin and as well as to immunoglobulin from other species. While the mechanism of human anti-murine antibody interference has been well characterized, the time course over which this interference occurs and the susceptibility of different immunoassay procedures to human anti-murine antibody interference from patients with human anti-murine antibody have not been as well described. We report on the time course of interference in assays for cardiac markers for two patients with human anti-murine antibodies. We measured creatine kinase MB isoenzyme (CKMB) and troponins I and T using three different vendors' immunoassay procedures. Our results demonstrate that assay interference due to human anti-murine antibody interference is a transient phenomenon. In one of our patients, human anti-murine antibody interference appeared suddenly, peaked approximately 9 days following its appearance, and gradually resolved over the next 3 weeks. In addition, we found that immunoassay methods from different vendors can show highly variable interference effects when human anti-murine antibody-containing specimens are analyzed.

Aged↗

Multiple regression analysis of interference effects from a hemoglobin-based oxygen carrier solution.

The use of hemoglobin-based oxygen carrier solutions in patients requiring blood transfusion will necessitate that clinical laboratories have mechanisms in place to evaluate the potential interference effect of these substances on testing methods. Because these oxygen carrier solutions contain acellular hemoglobin, but do not contain many of the intracellular enzymes and ions present in erythrocytes, interference effects from blood substitutes may be quite different when compared to in vivo or in vitro lysis of erythrocytes. We evaluated the potential interference effect of Diaspirin Cross-linked Hemoglobin on 29 different clinical laboratory analytes. Various combinations of these analytes were tested using the Hitachi 747 and 911 systems, a Beckman CX3, an Abbott AxSym, a Bayer Immuno I, and a Dade ACA IV; a total of 60 analyte/instrument combinations. We used the method of multiple regression analysis to classify interferences as analyte-dependent, analyte-independent, or a combination of the first two types. The presence of clinically significant test interference was derived by using the criteria for maximum allowable error specified in the Clinical Laboratory Improvement Amendments of 1988. Using these criteria, we found significant interference from Diaspirin Cross-linked Hemoglobin with 13 of 29 analytes tested. Interference was noted with the Hitachi 747 and 911 methods for albumin, alkaline phosphatase, total and conjugated bilirubin, cholesterol, total carbon dioxide, iron, lactate dehydrogenase, magnesium, total protein, and triglyceride. In addition, Diaspirin Cross-linked Hemoglobin interfered with measurement of L-lactate using the ACA IV and minor interference was noted with glucose measured using the Beckman CX3. Data from the interference studies was graphically displayed in the form of interference plots. These plots show the maximum allowable test error, due to Diaspirin Cross-linked Hemoglobin, as a function of analyte and interferent concentrations. Evaluation of the potential interference effect of hemoglobin-based oxygen carrier solutions with use of multiple regression analysis and graphical display of the resultant data in the form of interference plots allows for more reliable reporting of test results from specimens containing these products.

Aspirin↗

Topical morphine in a canine model: a pilot study.

OBJECTIVE: To determine if topical morphine can enter the synovial cavity and the effect of ultrasound on this process. DESIGN: A randomized control trial to investigate which body fluids morphine enters after topical application. SETTING: A university animal laboratory. SUBJECTS: Ten mongrel dogs raised by the Comparative Medicine Department. All animals were certified to be free of disease, all had received standard scheduled immunizations, and none had been used for any other research. INTERVENTION: Topical morphine and ultrasound or topical morphine and sham ultrasound was applied to the knees of the dogs. Samples were obtained afterward from synovial fluid, serum, and urine, and were analyzed for the presence of morphine. MAIN OUTCOME MEASURES: Blood samples were collected every 60 minutes for 240 minutes, urine samples were collected at 120 minutes and 240 minutes, and synovial joint fluid was collected at 120 minutes and 240 minutes. The process of collection and analysis was the same for dogs treated with topical morphine and ultrasound and those treated with topical morphine and sham ultrasound. Fisher's exact test was used to test for an association between the use of ultrasound and the presence of morphine in the synovial fluid, serum, or urine. Two-sample t tests were used to test for group differences in mean body weight. RESULTS: All samples (synovial fluid, serum, and urine) were negative at time zero. All of the subsequent serum samples were negative for morphine. Two or three of the dogs in each group of five (ultrasound or sham ultrasound) had positive urine and synovial fluid samples at 120 and 240 minutes. Ultrasound did not affect the results. Body weight of the dogs influenced the results, with lighter animals having a significantly larger percentage (p=.03) of synovial fluid samples positive for morphine. CONCLUSION: Ultrasound did not affect the absorption of topical morphine in this canine model. Body weight may have influenced the results. Dogs that tested positive for morphine in synovial fluid had a lower mean body weight than dogs that did not test positive (p=.03).

Administration, Topical↗

Simplified interpretative format for assessing test interference: studies with hemoglobin-based oxygen carrier solutions.

Substances such as hemoglobin that interfere with analytical processes are recognized as a frequent source of error in laboratory medicine. Standard guidelines for assessment of test interferences assume that interference effects are not related to the concentration of the analyte being measured. However, previous investigations have demonstrated that interference effects can be markedly different, depending on the concentrations of interferent and analyte within the specimen. An experimental protocol for investigating these different types of interference effects has been developed. This protocol utilizes an orthogonally arranged matrix with progressively increasing concentrations of analyte and interferent. Evaluation of the measured analyte concentrations in specimens within the matrix using multiple regression analysis allows the magnitude, direction, and significance of each type of interference to be determined. Unfortunately, implementation of the interference data derived from the multiple regression analysis for judging the clinical acceptability of test results when an interferent is present is difficult. We describe a two-dimensional graphical format for evaluating the clinical acceptability of test results, based on criteria established under the Clinical Laboratory Improvement Amendments of 1988, in specimens containing hemoglobin-based oxygen carrier solutions.

Aspirin↗

Enzymatic markers of gallstone-induced pancreatitis identified by ROC curve analysis, discriminant analysis, logistic regression, likelihood ratios, and information theory.

We investigated the diagnostic utility of frequent serial determinations of aspartate aminotransferase, alanine aminotransferase (ALT), lipase, amylase, and the lipase/amylase (L/A) ratio for distinguishing patients with acute pancreatitis due to biliary obstruction from those with acute pancreatitis due to other pathogenesis. Analyzed were enzyme activities obtained at admission and peak enzyme activities identified retrospectively from serial measurements in 53 patients with acute pancreatitis due to various causes. We evaluated the data with multiple statistical tools. Discriminant analysis and logistic regression revealed the diagnostic significance of ALT at initial and peak values, and the maximum information provided by peak ALT was confirmed by both logistic regression and stratum-specific likelihood ratios. Stratum-specific likelihood ratios showed peak ALT > 150 U/L was highly diagnostic of biliary pancreatitis. The L/A ratio, either at admission or at peak, was the only other significant variable for identifying patients with acute pancreatitis due to biliary obstruction. A multivariate logistic discriminant function including ALT and the L/A ratio significantly discriminated biliary acute pancreatitis from pancreatitis due to other causes. Evaluation of initial and peak enzyme data by information theory revealed that the optimal test depended on disease prevalence. Initial ALT activities were the test of choice for identifying biliary pancreatitis, up to a disease prevalence of approximately 0.75. At disease prevalence > 0.75, the initial L/A ratio provided the greatest amount of diagnostic information.

Acute Disease↗

Diagnostic accuracy of pancreatic enzymes evaluated by use of multivariate data analysis.

We analyzed pancreatic enzyme data from 508 patients with suspected pancreatitis by neural network analysis, by an Expert multirule generation protocol, and by receiver-operator characteristic (ROC) curve analysis of a single test result. Neural network analysis showed that use of lipase provided the best means for diagnosing pancreatitis. Diagnostic accuracies achieved by using amylase only, lipase only, and amylase and lipase in combination were 76%, 82%, and 84%, respectively. Use of the Expert rule generation protocol provided a diagnostic accuracy of 92% when rules for single and multiple samplings were combined. ROC curve analysis for initial enzyme activities showed the maximal diagnostic accuracy to be 82% and 85% for amylase and lipase, respectively; use of peak enzyme activities yielded accuracies of 81% and 88%, respectively. The evaluation of laboratory test data should include analysis of the diagnostic accuracy of laboratory tests by multivariate techniques such as neural network analysis or an Expert systems approach. Multivariate analysis should allow for a more realistic assessment of the diagnosis accuracy of laboratory tests because all the available data are included in the evaluation.

Amylases↗

Laboratory error undetectable by customary quality control/quality assurance monitors.

The preanalytical, analytical, and postanalytical rates of laboratory error have not been studied extensively. We evaluated the preanalytical, analytical, and postanalytical components of laboratory error in 438 consecutive samples submitted to a clinical chemistry laboratory for measurement of creatinine concentrations in plasma. We performed red blood cell antigen determinations to establish patient-sample identity, repeated analysis of creatinine in duplicate to detect analytical error, and tracking of patient specimens from receipt by the laboratory to entry of the laboratory result in the patient's information system record. We found a total error rate of 9.36%. A breakdown of the total error rate into its preanalytical, analytical, and postanalytical components revealed error rates of 0.00%, 8.90%, and 0.46%, respectively. These results suggest that preanalytical and postanalytical error, which are not usually detectable by common quality control strategies, are not major sources of laboratory error. Further work is needed to reduce the unacceptably high rate of analytical errors.

Chemistry, Clinical↗

Clinical chemistry.

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Chemistry, Clinical↗

Diagnostic and prognostic utility of phospholipase A activity in patients with acute pancreatitis: comparison with amylase and lipase.

We compared the diagnostic and prognostic utility of phospholipase A (PLA; EC 3.1.1.4) for acute pancreatitis with that of amylase and lipase by analysis of sera from 151 consecutive patients presenting with abdominal pain in whom assays of serum amylase and (or) lipase had been ordered. We determined the diagnostic accuracy for both the initial and the peak enzyme activities. Maximal diagnostic accuracy obtained for the initial activities of amylase, lipase, and PLA was 0.83, 0.83, and 0.76 at cutoff values of 650, 650, and 41 U/L, respectively. Use of peak enzyme activities showed maximal diagnostic accuracy of 0.85, 0.86, and 0.73 at cutoff values of 650, 1050, and 42 U/L, respectively. Receiver-operator characteristic curve analysis revealed the diagnostic performance of amylase and lipase to be similar, whereas that of PLA was almost random and not incremental. As with amylase and lipase, PLA activities in sera showed no relation to patients' survival; three patients who died after an attack of acute pancreatitis failed to demonstrate the dramatic increases in PLA activity previously described. We conclude that assessing the severity of acute pancreatitis by using enzyme activities still remains problematical. Measurements of amylase or lipase activities provide similar diagnostic discrimination when appropriate cutoff values are used and remain the methods of choice for diagnosis of acute pancreatitis.

Acute Disease↗

Effect of reticulocytosis on lactate dehydrogenase isoenzyme distribution in serum: in vivo and in vitro studies.

We investigated the effect of reticulocytosis on the lactate dehydrogenase (LD; EC 1.1.1.27) isoenzyme LD1/LD2 ratio in patients with and without evidence of hemolytic disease. Analysis of sera from patients with reticulocytosis and in vivo hemolysis showed a mean LD1/LD2 ratio of 0.92 compared with a ratio of 0.69 in patients with in vivo hemolysis and normal reticulocyte counts. Determination of LD isoenzymes in erythrocyte lysate revealed significantly increased LD1/LD2 ratios for patients with marked reticulocytosis compared with those for patients with normal-to-minimal increases in reticulocytes. Finally, separation of mature erythrocytes and reticulocytes by flow cytometry revealed marked differences in the LD1/LD2 isoenzyme distribution between these two cell types. The ability of hemolysis to cause a "flipped" LD1/LD2 ratio is dependent on the proportion of the hemolyzed cells that are reticulocytes.

Cells, Cultured↗

Measuring carboxypeptidase A activity with a centrifugal analyzer: analytical and clinical considerations.

This adaptation of a commercially available kit for automated measurement of carboxypeptidase A (CPA; EC 3.4.17.1) activity in serum with the Cobas Bio centrifugal analyzer extends the linear range to an activity concentration of 82 U/L. Results obtained by the described method correlated closely (r = 0.98) with those by the manual kit method. The reference interval for 150 apparently normal individuals was 0.12-0.91 U/L. Total CVs of the method ranged from 4.0% to 13.1%. Bilirubin and glucose decreased the CPA activity in serum by as much as 98% and 26%, respectively. Substantial CPA activity was found in pancreatic tissue, with little activity in intestinal tissue. CPA activity was not as widely distributed in extra-pancreatic tissues as were amylase and lipase activities. Peak activities of CPA, amylase, and lipase in the sera of patients with acute pancreatitis were significantly correlated (r = 0.45 to 0.78, P less than 0.05-0.01). The optimized diagnostic efficiency of CPA for acute pancreatitis was 0.85 at a cutoff value of 5 U/L. Amylase and lipase exhibited similar optimized efficiencies, and parallel testing did not significantly improve diagnostic accuracy. We conclude that automated analysis for CPA activity, even in the absence of interferences, does not add to the diagnostic information provided by the widely available assays for amylase and lipase activity.

Acute Disease↗