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Biomedical subjects

R H Christenson

Publications and source records attributed to R H Christenson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Proposals from IFCC Committee on Standardization of Markers of Cardiac Damage (C-SMCD): recommendations on use of biochemical markers of cardiac damage in acute coronary syndromes.

This paper presents evidence and suggestions from the IFCC C-SMCD on the use of biochemical markers for the triage diagnosis of acute coronary syndromes. There is general agreement that both 'early' and 'definitive' biochemical markers are necessary and that these assays must be available with a turnaround time of 1 h or less. Currently, myoglobin is the marker that most effectively fits the role as an 'early' marker, whereas 'definitive' markers are cardiac troponins. Since the sensitivity of the initial electrocardiogram is only 50% for detecting myocardial infarction, the use of biochemical markers may significantly contribute to the early diagnosis. New sensitive biochemical markers, particularly the cardiac troponins, are presently the best criterion to detect the presence of small myocardial cell damage. Two decision limits are probably needed for the optimum use of troponins: a low abnormal value suggesting the presence of myocardial damage and a higher value suggesting the diagnosis of myocardial infarction. Additional studies should be performed to establish limits for each commercially available assay. Finally, it is recognized that there is no need for the use of any biochemical marker when the clinical diagnosis is unequivocal, other than for diagnosing reinfarction, estimating the infarct size, and monitoring thrombolytic therapy.

Acute Disease↗
PubMed1999

Proposals from the IFCC Committee on Standardization of Markers of Cardiac Damage (C-SMCD): strategies and concepts on standardization of cardiac marker assays.

The search for sensitive and specific biochemical markers of cardiac damage has resulted in development of methods for the measurement of cardiac markers such as myoglobin, CK-MB mass and the cardiac troponins (cardiac troponin I and cardiac troponin T). There have been new clinical applications of already known markers based on improved, reformulated methods which often depend on advanced technologies. These developments are connected with analytical and interpretative challenges for the laboratory manager and for the clinician. In this situation, it is essential that international professional societies develop comprehensive and carefully elaborated guidelines for the quality management and use of these measurements and their results. Several professional associations have formed committees working on different issues regarding the measurement of biochemical markers of cardiac damage. Recognizing the huge interest in this field and substantial diagnostic relevance of these markers, the IFCC has established the Committee on "Standardization of Markers of Cardiac Damage" (C-SMCD) in 1997 inviting the already operating American and European groups to designate some of their members into the new committee. The task of the IFCC C-SMCD is to coordinate the different activities of the national groups, with preparation of international documents and recommendations under the auspices of IFCC and to initiate various standardization activities. The establishment of consensus/reference methods as well as development of primary and secondary matrix reference materials for markers of cardiac damage are extremely important in order to achieve comparability of test results, thus leading to an effective patient care.

Biomarkers↗
PubMed1999

Standardization of creatine kinase-MB (CK-MB) mass assays: the use of recombinant CK-MB as a reference material.

BACKGROUND: The AACC assembled a committee to identify and validate a standard creatine kinase MB isoenzyme (CK-MB) material to improve the comparability of CK-MB mass assays. METHODS: Three protocols were used. In protocol I, various CK-MB materials prepared in different matrices were screened as candidate standards. In protocol II, participating manufacturers calibrated their systems with concentrates of human heart CK-MB and then tested 20 patient samples to evaluate calibration bias. In protocol III, participating manufacturers calibrated their immunoassay systems using recombinant CK-MB2 (rCK-MB2) diluted into their respective sample diluents and measured 50 samples. RESULTS: Candidate materials showed high recovery in stripped human serum, but bias improved only from 59% to 38%. These data led to the use of human heart CK-MB diluted in each manufacturer's sample diluent. This strategy reduced bias from 31% to 15%. Because human heart CK-MB is difficult to provide, a lyophilized source of CK-MB2 was identified. rCK-MB2 was shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, reversed-phase HPLC, intrinsic protein fluorescence, circular dichroism, agarose gel electrophoresis, immunoreactivity studies, high and low temperature stability, and reconstituted stability to be equivalent to human heart CK-MB. Calibration of immunoassay systems with rCK-MB2 added into each respective manufacturer's sample diluent showed a 13% between-manufacturer bias. CONCLUSION: Lyophilized rCK-MB2 was determined suitable for use as a reference material for CK-MB mass assays.

Calibration↗
PubMed1999

Simultaneous rapid measurement of whole blood myoglobin, creatine kinase MB, and cardiac troponin I by the triage cardiac panel for detection of myocardial infarction.

This multicenter study evaluated the Biosite Triage(R) Cardiac Panel as a quantitative, multimarker, whole blood system for the detection of acute myocardial infarction (MI). Optimum cutoffs for the discrimination of acute MI (n = 192 patients, 59 with MI) as determined by ROC curve analyses were as follows: 0.4 microgram/L for cardiac troponin I (cTnI); 4.3 microgram/L for the creatine kinase MB isoenzyme (CK-MB); and 107 microgram/L for myoglobin. The Triage Panel showed the following concordances for detection or rule-out of MI compared with established devices: cTnI >89%; CK-MB >81%; myoglobin >69%. No significant differences were present between methods for the same marker. Diagnostic efficiencies demonstrated comparable sensitivities and specificities for the diagnosis of MI in patients presenting with symptoms compared with the Dade, Beckman, and Behring CK-MB, cTnI, and myoglobin assays; the ratio of sensitivity to specificity for each marker was as follows: cTnI, 98%:100%; CK-MB, 95%:91%; myoglobin, 81%:92%. The areas under the ROC curves for the Biosite myoglobin, CK-MB, and cTnI were 0.818, 0.905, and 0.970, respectively; the areas were significantly different, P <0.05. In patients with skeletal muscle injury and renal disease, the Triage cTnI showed 94% and 100% specificity, respectively. The Triage panel offers clinicians a whole blood, point-of-care analysis of multiple cardiac markers that provides excellent clinical sensitivity and specificity for the detection of acute MI.

Creatine Kinase↗
PubMed1999

Multicenter clinical and analytical evaluation of the AxSYM troponin-I immunoassay to assist in the diagnosis of myocardial infarction.

We evaluated the AxSYM troponin I (cTnI) immunoassay for assisting in the detection of acute myocardial infarction (AMI). At four sites, the total imprecision (CV) over 20 days was 6.3-10.2%. The minimum detectable concentration was 0.14 +/- 0.05 microgram/L. Comparison of cTnI measurements between the AxSYM and Stratus (n = 406) over the dynamic range of the AxSYM assay demonstrated good correlation, r = 0.881, with a proportional bias: AxSYM cTnI = 3.50(Stratus cTnI) - 1. 10. The confidence intervals (95%) for the slope and intercept were 3.39-3.64 and -1.32 to -0.95, respectively. The expected cTnI concentration in healthy individuals was </=0.5 microgram/L, whereas the ROC curve-determined cutoff for AMI was 2.0 microgram/L. This gave a diagnostic sensitivity of 91.8% and specificity of 92.4% when tested in serial samples collected within 24 h of admission in 633 patients presenting with chest pain, of which 122 had an AMI. The concordances of the AxSYM cTnI with the Stratus cTnI, OPUS cTnI, and Access cTnI were 95.3%, 95.1%, and 94.3%, respectively, from patients with suspected AMI. The AxSYM cTnI demonstrated excellent clinical specificity, >/=96%, in skeletal muscle injury, chronic renal disease, and same-day noncardiac surgery patients.

Evaluation Studies as Topic↗
PubMed1998

Value of serial troponin T measures for early and late risk stratification in patients with acute coronary syndromes. The GUSTO-IIa Investigators.

BACKGROUND: The baseline cardiac troponin T (cTnT) level strongly predicts short-term mortality in acute coronary syndromes, but the added value of later measures to predict short- and long-term outcome and in the context of baseline clinical characteristics is unclear. METHODS AND RESULTS: Relations between baseline, peak, and 8- and 16-hour (late) cTnT results and outcomes were assessed in 734 patients in a GUSTO-IIa substudy. Proportional-hazards models assessed the prognostic information gained from late cTnT when added to a mortality model containing the baseline cTnT result and clinical factors. At baseline, 260 patients were cTnT-positive (>0.1 ng/mL), 323 became positive later, and 151 remained negative (</=0.1 ng/mL). Mortality at 30 days was 10% in the baseline-positive group, 5% in late-positive patients, and 0% in negative patients. After adjustment for baseline characteristics, any positive cTnT result predicted 30-day mortality (baseline, chi2=8.96, P=0.0113; 8-hour, chi2=6.51, P=0.0107; 16-hour, chi2=8.40, P=0.0038). Both the 8- and the 16-hour results added to the strength of the baseline result (baseline+8-hour, chi2=12.04, P=0.0072; baseline+16-hour, chi2=13.52, P=0.0036). Only age and ST-segment elevation were stronger predictors of 30-day mortality than baseline cTnT; results were similar for prediction of 1-year mortality. Most of the mortality difference between cTnT-positive and -negative patients occurred within the first 30 days. CONCLUSIONS: The cTnT level is a strong, independent predictor of short-term outcome in acute coronary syndromes. The addition of later samples to a baseline level is useful to evaluate the risk of serious cardiac events.

Acute Disease↗
PubMed1998

Production and characterization of monoclonal antibodies to human carbonic anhydrase III.

Carbonic anhydrase III (CAIII) is a cytosolic protein found almost exclusively in slow-oxidative skeletal muscle fibers. Upon excessive skeletal muscle activity or damage, CAIII is rapidly released into serum. CAIII is not found in cardiac muscle, whereas the muscle protein myoglobin (Myo) is found in skeletal and cardiac muscle. Because CAIII and Myo are released from injured muscle in a constant ratio, an increase in the Myo/CAIII ratio may be useful as an early diagnostic indicator of acute myocardial damage. Although several reliable Myo immunoassays have been established, no similar CAIII immunoassay is commercially available. We produced murine monoclonal antibodies (MAbs) to human CAIII using standard immunization and cell fusion procedures. Using an enzyme-linked immunoadsorbent assay (ELISA), three MAbs showed strong immunoreactivity with CAIII, but low to moderate levels of cross-reactivity with closely related isoenzymes CAI and CAII. The three MAbs demonstrated unique patterns of reactivity toward CAI, CAII, and CAIII, suggesting that different CAIII epitopes are recognized by the three MAbs. Specificity was further examined by Western blot analysis. These MAbs demonstrated potential for use in the development of an immunoassay for CAIII, and for investigating the biology of skeletal muscle injury in vivo.

Animals↗
PubMed1998

Abbott AxSYM Vancomycin II assay: multicenter evaluation and interference studies.

The authors evaluated the performance characteristics of the Abbott AxSYM Vancomycin II immunoassay in sera of patients with (n = 93 samples) and without (n = 327 patients) renal dysfunction. Correlation of vancomycin measurements with the Abbott AxSYM Vancomycin, Abbott TDx/TDxFLx, Syva enzyme-multiplied immunoassay technique (EMIT), DuPont automated chemistry analyzer (ACA), and high-performance liquid chromatography methods showed acceptable correlation as indicated by: slope values >0.95, r-values >0.97, y-intercepts <1.7 microg/ml, and S(y/x) ranging from 9% to 15% of the average vancomycin value. The AxSYM Vancomycin II assay showed acceptable correlation with AxSYM vancomycin, TDx/TDxFLx, and high-performance liquid chromatography methods in 93 samples from patients with renal dysfunction. This monoclonal antibody-based assay showed no apparent interference from the presence of human antimouse antibody (HAMA) or the microbiologically inactive vancomycin crystalline degradation product (CDP). The authors conclude that the AxSYM Vancomycin II assay showed satisfactory agreement with other methods tested in this study.

Anti-Bacterial Agents↗
PubMed1998

Cardiac troponin T and cardiac troponin I: relative values in short-term risk stratification of patients with acute coronary syndromes. GUSTO-IIa Investigators.

We compared cardiac troponins T (cTnT) and I (cTnI) collected within 3.5 h of ischemic symptoms for predicting clinical outcomes in 770 patients. cTnT (cutoff > 0.1 microgram/L) and cTnI (cutoff > 1.5 micrograms/L) were concordant (both positive or negative) in 90.4% of patients. Among discordant results, 66 were cTnT positive and cTnI negative vs 8 who showed the reverse (P < 0.001). Five cTnT-positive and cTnI-negative patients died within 30 days; none who were cTnT negative and cTnI positive died. cTnT showed a slightly greater association (chi 2 = 18.0, P < 0.001) with 30-day mortality than cTnI (chi 2 = 12.5, P = 0.002). The area of the ROC curve for predicting 30-day mortality was significantly larger (Z = 2.08; P = 0.0375) for cTnT, at 0.68 [95% confidence interval (CI) 0.60-0.75], compared with cTnI, at 0.64 (95% CI 0.56-0.72). When cTnI and the electrocardiogram (ECG) were put in a logistic multiple regression model, cTnT added significant information (chi 2 = 8.03, P = 0.045); however, cTnI did not add to a model containing cTnT and the ECG (chi 2 = 0.84, P = 0.657). cTnT provided more information than cTnI for predicting 30-day mortality early after presentation with acute coronary syndromes.

Aged↗
PubMed1998

Cardiac troponin I measurement with the ACCESS immunoassay system: analytical and clinical performance characteristics.

We evaluated the ACCESS cardiac troponin I (cTnI) immunoassay as a marker for myocardial infarction (MI). Total imprecision was 6.0% to 13.5%, the minimum detectable concentration was 0.007 microg/L, and the limit of quantitation was 0.046 microg/L. Comparison of cTnI measurement between the ACCESS and Stratus systems (n = 114) showed a proportional difference: ACCESS cTnI = 0.0996 Stratus cTnI + 0.049 microg/L (r = 0.811). Fifty-nine of 61 ambulatory patients without cardiac symptoms had no detectable cTnI (95% range, 0.00 to 0.025 microg/L). The optimum cutoff for discriminating MI (n = 289, 45 with MI) was 0.15 microg/L by receiver operator characteristic curve analysis; at this cutoff, the ACCESS cTnI assay showed a sensitivity of 88.9% (95% CI, 79.7-98.1%) and specificity of 91.8% (95% CI, 88.4-95.2%). The ACCESS cTnI assay results showed 89.4% and 93.0% concordance with the MB isoenzyme of creatine kinase (CK-MB) mass and Stratus cTnI results, respectively, for classification of patients with suspected MI. The ACCESS cTnI assay appears to show sensitivity and specificity comparable with those of both CK-MB mass and Stratus cTnI assays for the diagnosis of MI in patients presenting within 12 h of onset of symptoms.

Adult↗
PubMed1998

Biochemical markers of the acute coronary syndromes.

The acute coronary syndromes represent a continuum of myocardial ischemia ranging from angina, reversible tissue injury --> unstable angina, frequently associated with minor myocardial damage --> myocardial infarction and extensive tissue necrosis. Historically, coronary artery disease assessment has been mainly binary, using WHO criteria of symptoms, electrocardiography, and biochemical markers. The creatine kinase-MB isoenzyme (CK-MB) has been a benchmark for markers, but it is not specific for myocardium. Cardiac-specific isoforms of troponin T and I have emerged as sensitive myocardial infarction (MI) indicators and, importantly, for risk stratification of acute coronary syndrome patients. In addition to markers of myocardial cell necrosis, markers of plaque disruption (C-reactive protein and serum amyloid A), "angry" platelets (P-selectin), ischemia (glycogen phosphorylase-BB isoenzyme), and the procoagulant state and thrombosis (soluble fibrin) have potential use. Also, CK-MB and myoglobin have been combined with clinical indicators for monitoring reperfusion after thrombolytic therapy. Biochemical markers will continue to be an important clinical adjunct for MI diagnosis, risk assessment, and reperfusion monitoring in the future.

Acute Disease↗
PubMed1998

Analytical and clinical performance characteristics of Tandem-MP Ostase, a new immunoassay for serum bone alkaline phosphatase.

The performance characteristics of the Tandem-MP Ostase assay, a new microplate immunoassay for bone-specific alkaline phosphatase (bone ALP; EC 3.1.3.1) in human sera, are described. Bone ALP is bound to streptavidin-coated microwells by a single biotinylated anti-bone ALP monoclonal antibody. Antigen is detected by the addition of p-nitrophenyl phosphate. The assay is performed at room temperature in <90 min. Imprecision was 2.3-6.1% with a detection limit of 0.6 microg/L. Method comparison of bone ALP measurements with the Tandem-MP Ostase assay and the mass-based Tandem-R Ostase assay (n = 285) indicated regression statistics of Tandem-MP Ostase = 1.03 Tandem-R Ostase + 0.22 microg/L, S(y/x) = 4.0 microg/L, r = 0.97. Serum bone ALP values in apparently healthy men and in pre- and postmenopausal women were also similar between the two Ostase assay formats. Liver ALP reactivity determined using the slope and heat inactivation methods was similar in both Ostase assays. Liver ALP reactivity ranged from 3 microg/L (heat inactivation) to 6 microg/L (slope method) per 100 U/L of liver ALP activity, whereas bone ALP reactivity was 37 microg/L per 100 U/L of bone ALP activity, indicating a liver ALP relative reactivity of 8.1-16.2%. Similar results were obtained with the Alkphase-B bone ALP immunoassay. The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. In conclusion, the Tandem-MP Ostase assay for serum bone ALP is a rapid, simple, robust nonisotopic alternative to the Tandem-R Ostase immunoradiometric assay that provides an accurate and sensitive assessment of bone turnover.

Adolescent↗
PubMed1997

Assessment of coronary reperfusion after thrombolysis with a model combining myoglobin, creatine kinase-MB, and clinical variables. TAMI-7 Study Group. Thrombolysis and Angioplasty in Myocardial Infarction-7.

BACKGROUND: Several biochemical markers have been investigated for the noninvasive assessment of reperfusion after myocardial infarction. Because myoglobin is released very soon after myocardial injury and clears rapidly after reperfusion, it may prove to be an excellent marker of occlusion and reperfusion. METHODS AND RESULTS: We examined the relation between various myoglobin measures and Thrombolysis In Myocardial Infarction (TIMI) flow grade in 96 patients enrolled in a study of front-loaded thrombolysis who underwent 90-minute angiography. We also combined myoglobin measures with models that include clinical and creatine kinase-MB variables. The myoglobin level measured within 10 minutes of acute angiography showed the best overall performance and was used for later analyses. Of the clinical variables examined, only time from symptom onset to thrombolysis and chest pain grade at angiography discriminated among TIMI flow grades. Combining the 90-minute myoglobin level and these clinical variables showed a significant difference (P<.0001) between both TIMI 3 versus TIMI 0 through 2 and TIMI 2 or 3 versus TIMI 0 or 1 flow. When the 90-minute myoglobin level was added to an established predictive model containing clinical variables and creatine kinase-MB measures, its contribution remained significant (P=.044). The area under the receiver operator characteristic curve for this combined model was .88. CONCLUSIONS: A single myoglobin measurement obtained 90 minutes after the start of thrombolysis, combined with select clinical variables and creatine kinase-MB levels, enhances the noninvasive prediction of reperfusion after myocardial infarction.

Adult↗
PubMed1997

Characteristics of a 20-minute whole blood rapid assay for cardiac troponin T.

OBJECTIVES: A qualitative whole blood rapid assay for cardiac troponin T (cTnT) was examined. The assay uses the same antibodies as for a benchmark ELISA, but the capture and detection roles were switched to enhance specificity. DESIGN AND METHODS: The cTnT Rapid Assay and ELISA were compared in 643 samples from patients having myocardial infarction, coronary artery bypass surgery, ischemic heart disease, musculoskeletal disease, renal failure, or other noncardiac conditions. Concordance between the methods was compared using the McNemar Test and cTnT cutoff of 0.2 micrograms/L. RESULTS: For the "cutoff" of 0.2 micrograms/L, concordance between the cTnT Rapid Assay and ELISA was in the range of 90-95% for each group except the renal failure patients, where concordance was 77.9%. There was no significant difference between the cTnT Rapid Assay and ELISA, except in the renal failure and ischemic heart disease patients, where there was a greater number (p < 0.05) of cTnT Rapid Assay negative results when the ELISA was > 0.2 micrograms/L. Overall concordance between the cTnT Rapid Assay and CK-MBmass was 78%. CONCLUSION: The McNemar test indicated that the cutoff for the cTnT Rapid Assay was 0.2 micrograms/L. Evidently the lower concordance among renal failure and ischemic heart disease patients reflects higher cTnT specificity for the Rapid Assay that was conferred by switching the capture and detection antibodies.

Adolescent↗
PubMed1997

Biochemical markers of bone metabolism: an overview.

OBJECTIVES: An overview of biochemical markers of bone metabolism is presented along with indications for their clinical utilization. DESIGN AND METHODS: The structure, cyclical metabolism, and hormone regulation of bone is reflected by markers of resorption, formation and/or turnover. Markers of resorption representing degradation of type 1 collagen, include N-telopeptides, C-telopeptides, hydroxyproline, and the collagen crosslinks pyridinoline and deoxypyridinoline; acid phosphatase, a marker of osteoclast activity, and urinary calcium are also indicators of bone resorption. Bone formation markers indicate osteoblast activity; bone-specific alkaline phosphatase and the N-terminal and C-terminal extension peptides of procollagen reflect formation of organic matrix in bone. Osteocalcin, produced by osteoblasts but also released during osteoclastic degradation, may indicate either formation when resorption and formation are coupled or turnover when they are uncoupled. RESULTS: Bone markers respond to intervention more rapidly than techniques such bone mineral density. Resorption markers respond approximately 1 to 3 months after intervention; markers of formation respond later, after 6 to 9 months. Bone markers may add useful information for assessing fracture risk and for monitoring osteoporosis, Paget's disease of bone, cancer metastasis, and metabolic disease. Various therapeutic interventions may affect release of some bone markers. CONCLUSION: Bone disease has high prevalence in adults so bone markers will become even more important for assessing fracture risk and monitoring therapy as populations age. Characteristics of bone markers are dependent on biology and the assay used. Substantial work remains in characterizing existing assays, identifying better markers and performing the clinical studies to define which bone markers should be measured and when.

Acid Phosphatase↗
PubMed1997

In vitro interference of the red cell substitute pyridoxalated hemoglobin-polyoxyethylene with blood compatibility, coagulation, and clinical chemistry testing.

OBJECTIVES: Pyridoxalated hemoglobin-polyoxyethylene (PHP) is a prototypical red cell substitute approved for phase I studies. Peripheral blood smears of human blood mixed with PHP in 1 to 4 g/dL concentrations showed dose-dependent red cell aggregation and rouleaux. Whether this aggregation limits interpretation of blood compatibility testing and whether the intense coloration of serum or plasma containing PHP affects routine coagulation and clinical chemistry measurements was tested. DESIGN: In vitro studies. SETTING: University hospital laboratory. PARTICIPANTS: Four healthy volunteers, blood types A, B, AB, and O. All were Rh+. MEASUREMENTS AND MAIN RESULTS: ABO typing, Rh typing, and antibody screening and coagulation studies were performed on blood: PHP admixtures having final concentrations of 1, 2, and 4 g/dL. For clinical chemistry interference studies, known concentrations of analytes were added to a serum matrix containing PHP. ABO (forward) and Rh typing showed no interference in the three concentrations tested. Reverse ABO typing and antibody screening showed rouleaux at 4 g/dL, which corrected with routine saline replacement. Partial thromboplastin time (PTT), prothrombin time (PT), and fibrinogen showed no clinically significant differences from the controls. Results for electrolytes, renal function analytes, and markers of cardiac injury were acceptable by standard laboratory methods. However, results of liver function tests were unacceptable in PHP-containing specimens. CONCLUSIONS: PHP-induced aggregation was observed with high PHP concentration; however, compatibility testing was not affected because agglutination was corrected by saline replacement, which is standard practice. Although routine blood banking, coagulation, and most clinical chemistry analytes can be measured reliably, alternative methods and strategies are needed for assessing liver function in the presence of PHP.

Blood Coagulation↗