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Biomedical subjects

F S Apple

Publications and source records attributed to F S Apple.

At least 19 recordsLinked to original sources
PubMed2001

Cardiac troponin assays: analytical issues and clinical reference range cutpoints.

A recently published consensus document from the European Society of Cardiology and American College of Cardiology emphasized the unique role cardiac troponin monitoring plays in redefining acute myocardial infarction. The cardiology community has now established criteria to define both the reference cutpoints and acceptable imprecision for troponin assays, which complement previous recommendations by the laboratory community. This article will review the analytical issues confronting laboratories, clinicians, and industry regarding troponin assay standardization, assay imprecision, and how clinical decision cutpoints should be established and implemented for clinical practice.

Biomarkers↗
PubMed2001

Analysis of the Albumin Cobalt Binding (ACB) test as an adjunct to cardiac troponin I for the early detection of acute myocardial infarction.

Human albumin has the ability to bind cobalt at the N-terminus. The exposure of circulating albumin to ischemic tissue alters the ability of albumin to bind cobalt, probably through a mechanism involving free-radical production. The Albumin Cobalt Binding (ACB) test measures the alteration in albumin metal binding, and elevation of the ACB test is thought to be an early indicator of myocardial ischemia. In a previous multicenter study of chest pain patients presenting to the emergency department (ED), this test demonstrated high negative predictive value and sensitivity in the sample collected at presentation for predicting cardiac troponin I (cTnI)-negative or cTnI-positive results 6-24 h later. Since the completion of that report, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) have redefined the criteria for the diagnosis of acute myocardial infarction (AMI). The data from the multicenter ACB study were re-examined using the new diagnostic criteria for AMI to determine if combining the ACB test with troponin improved the sensitivity of either assay used alone for early diagnosis of AMI. Assay values were compared to either the final discharge diagnosis made at each site or to a diagnosis of AMI using the strict application of the ESC/ACC guidelines. Using the criterion of physician's discharge diagnosis and using blood collected at ED presentation, the cTnI test alone had a sensitivity of 23.9%, and the ACB test alone had a sensitivity of 39.1%, but the sensitivity significantly increased to 55.9% (p < 0.001 over cTnI alone) when both tests were used in combination. The sensitivity of the combination of ACB and cTnI tests at the 1- to 6-h time-point was 86.7% and at the >6- to 12-h time-point was 93.5%, but they were not significantly improved over the cTnI test alone. In conclusion, using the new ESC/ACC criteria, the combination also resulted in a statistically significant higher diagnostic sensitivity on blood collected at presentation. These data indicate a possible role of the ACB test in the early triage of patients with chest pain.

Albumins↗
PubMed2001

Standardization of cardiac troponin I assays: round Robin of ten candidate reference materials.

BACKGROUND: Cardiac troponin I (cTnI) results vary 100-fold among assays. As a step toward standardization, we examined the performance of 10 candidate reference materials (cRMs) in dilution studies with 13 cTnI measurement systems. METHODS: Solutions of 10 cTnI cRMs, each characterized by NIST, were shipped to the manufacturers of 13 cTnI measurement systems. Manufacturers used their respective diluents to prepare each cRM in cTnI concentrations of 1, 10, 25, and 50 microg/L. For the purpose of ranking the cRMs, the deviation of each cTnI measurement from the expected response was assessed after normalization with the 10 microg/L cTnI solution. Normalized deviations were examined in five formats. Parameters from linear regression analysis of the measured cTnI vs expected values were also used to rank performance of the cRMs. RESULTS: The three cRMs demonstrating the best overall rankings were complexes of troponins C, I, and T. The matrices for these three cRMs values differed; one was reconstituted directly from the lyophilized form submitted by the supplier; one was submitted in liquid form, lyophilized at NIST, and subsequently reconstituted; and the third was evaluated in the liquid form received from the supplier. The cRM demonstrating the fourth best performance was a binary complex of troponins C and I supplied in lyophilized form and reconstituted before distribution. CONCLUSIONS: The cRMs demonstrating the best performance characteristics in 13 cTnI analytical systems will be included in subsequent activities of the cTnI Standardization Committee of the AACC.

Algorithms↗
PubMed2001

Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study.

BACKGROUND: The ability of the N-terminal region of human albumin to bind cobalt is diminished by myocardial ischemia. The characteristics of an assay based on albumin cobalt binding were assessed in suspected acute coronary syndrome patients and in a control reference population. The ability of the Albumin Cobalt Binding (ACB) Test measurement at presentation to predict troponin-positive or -negative results 6-24 h later was also examined. METHODS: We enrolled 256 acute coronary syndrome patients at four medical centers. Blood specimens were collected at presentation and then 6-24 h later. The dichotomous decision limit and performance characteristics of the ACB Test for predicting troponin-positive or -negative status 6 h-24 h later were determined using ROC curve analysis. Results for 32 patients could not be used because the time of onset of ischemia appeared to have been >3 h before presentation or was uncertain. The reference interval was determined by parametric analysis to estimate the upper 95th percentile of a reference population (n = 109) of ostensibly healthy individuals. RESULTS: Increased cTnI was found in 35 of 224 patients. The ROC curve area for the ACB Test was 0.78 [95% confidence interval (CI), 0.70-0.86]. At the optimum decision point of 75 units/mL, the sensitivity and specificity of the ACB Test were 83% (95% CI, 66-93%) and 69% (95% CI, 62-76%). The negative predictive value was 96% (95% CI, 91-98%), and the positive predictive value was 33% (95% CI, 24-44%). The within-run CV of the ACB Test was 7.3%. Results for the reference population were normally distributed; the one-sided parametric 95th percentile was 80.2 units/mL. CONCLUSIONS: This exploratory study suggests that the ACB Test has high negative predictive value and sensitivity in the presentation sample for predicting troponin-negative or -positive results 6-24 h later.

Acute Disease↗
PubMed2001

Postmortem blood free and total morphine concentrations in medical examiner cases.

This purpose of this study was to determine the relationships between postmortem free morphine and total morphine levels in a large series of medical examiner morphine and heroin related deaths. Free morphine, total morphine, and 6-monoacetylmorphine (6-MAM) concentrations were measured by gas chromatography-mass spectrometry (GC-MS) in 87 medical examiner cases over 20 months. The mean total morphine concentration, mean free morphine concentration, and mean percent free morphine for all cases were: 2.3 mg/L (SD 5.2 mg/L), 0.5 mg/L (SD 1.6 mg/L), and 19.4% (SD 22.8%); respectively. Regression analyses showed weak correlations between total and free morphine concentrations over the entire concentration range (0 to 36.6 m/L, r = 0.603, n = 91) and over a subset concentration range of 0 to 1.0 mg/L (r = 0.369, n = 54). Twenty-three out of 56 (41%) tested positive for 6-MAM, indicative heroin abuse cases. Lower total and free morphine concentrations and a higher percent free morphine were found in individuals with detectable 6-MAM. Comparing blood concentrations for cases with and without detectable 6-MAM demonstrated mean total morphine concentrations of 0.9 mg/L versus 2.1 mg/L (p = 0.05), mean free morphine concentrations of 0.3 mg/L versus 0.4 mg/L (p = 0.21), and mean percent free morphine of 34.7% versus 13.7% (p < 0.003), respectively. Our findings demonstrate higher free to total morphine ratios in individuals with detectable 6-MAM than in individuals without 6-MAM. The database established in this study may assist medical examiners in the evaluation of postmortem blood opiates regarding the cause of death in opiate related ingestion cases.

Autopsy↗
PubMed2000

Alterations in the expression and activity of creatine kinase-M and mitochondrial creatine kinase subunits in skeletal muscle following prolonged intense exercise in rats.

Creatine kinase (CK) isoenzymes are important structural and energy metabolism components in skeletal muscle. In this study, CK isoenzyme alterations were examined in male rats, with an 8% body mass weight attached to their tail. The rats were either forced to swim for 5 h (5S, n = 51), or were pre-trained for 8 days and then forced to swim for 5 h (T5S, n = 48). Rats were sacrificed either immediately (0 h PS), 3 h (3 h PS), or 48 h post-swimming (48 h PS). Serum CK was increased significantly (P < 0.01) 6.2- and 2.0-fold at 0 h PS following the 5S and T5S protocols, respectively. However, training (T5S protocol) significantly (P < 0.01) decreased CK release. Soleus and white gastrocnemius (WG) CK activity was significantly decreased following the 5S protocol (P < 0.05), but not following the T5S protocol. The CK-M activity of the soleus muscle was significantly (P < 0.05) decreased at 0 h PS following both the 5S and T5S protocols, and returned to control values at 3 h PS. The CK-M activity of the WG was significantly (P < 0.05) decreased at 0 h PS following the 5S protocol. Sarcomeric mitochondrial CK (sCK-Mit) was decreased significantly (P < 0.01) at 0 h PS (20%), 3 h PS (14%), 24 h PS (22%), and 48 h PS (15%) following the 5S protocol. However, sCK-Mit was decreased significantly (P < 0.01) only at 0 h PS (7%) following the T5S. The results of this study demonstrate that prolonged intense exercise causes a loss of skeletal muscle CK-M and sCK-Mit activity and that training prior to the prolonged intense exercise attenuates the exercise-induced CK-M and sCK-Mit loss in both red and white skeletal muscles.

Animals↗
PubMed2000

Monitoring plasma cardiac troponin I for the detection of myocardial injury after percutaneous transluminal coronary angioplasty.

The objective of this study was to detect myocardial injury defined by an increase of plasma cardiac troponin I (cTnI) following percutaneous transluminal coronary angioplasty (PTCA) and compare plasma cTnI with the risk of cardiac complications at 30 days. Plasma cTnI, creatine kinase (CK) MB, and total CK were determined in 83 patients before (baseline) and 6, 12 and 24 h after PTCA. Thirty-eight patients underwent conventional PTCA, 39 PTCA-stent and six rotational atherectomy. Patients with acute myocardial infarction (AMI) and increased pre-procedural cTnI >0.8 microg/l were categorized into group 1 (n=23). The remaining 60 patients (pre-procedural cTnI=0.8 microg/l) were categorized as follows: group 2 (n=15) AMI; group 3 (n=20) unstable angina (UA); group 4 (n=25) coronary artery disease (CAD). Twelve hours post-procedure, all three cardiac markers were more frequently increased over baseline in group 2 patients (40-60%) compared to patients in group 3 (5-29%, P<0.03) or group 4 (0.5-5%, P<0.01). This was also true for patients undergoing PTCA-stent compared to conventional PTCA or rotational atherectomy (27-40 vs. 4-14%, P<0.02). cTnI was more sensitive (60%) to detect release of myocardial protein after PTCA compared to total CK (47%) or CKMB (43%). A moderate increase of cTnI (0.8-1.5 microg/l) in groups 2, 3 and 4 was associated with higher risk of complications 30 days post-procedure.

Aged↗
PubMed2000

Loss of myocardial CK-MB into the circulation following 3.5 hours of swimming in a rat model.

The purpose of this study was to document alterations of creatine kinase-B (CK-B) in the left and right ventricles of rats and CK-MB release into the circulation following a single bout of stressful prolonged intense exercise. Male Sprague-Dawley rats, with 8% bodyweight attached to each tail, were forced to swim 3.5 hours and were then sacrificed immediately (0 h PS), 3 hours (3 h PS), 24 hours (24 h PS), and 48 hours (48 h PS) post swimming, respectively. Sedentary (control) rats were sacrificed at rest. Serum CK-MB mass increased 2.1 times (8.9 microg/L; p < 0.01 vs. controls of 4.3 microg/L) and 1.4 times (6.0 microg/L; P < 0.01 vs. controls) at 0 h PS, and 3 h PS, respectively, and returned to baseline at 24 h PS. Western blot analysis indicated that CK-B of the right ventricle decreased 14% (p < 0.05), 20% (p < 0.01), and 12% (p < 0.05) at 3h PS, 24h PS and 48h PS, respectively. The CK-B of the left ventricles decreased 34% (p < 0.05) at 0 h PS, returned to baseline at 3 h PS, and was increased 39% (P < 0.01) at 48 h PS. Our findings demonstrate that a single bout of stressful, prolonged, intense exercise resulted in CK-B subunit loss from the myocardium, resulting in increased serum CK-MB concentrations, an indication of myocardial injury.

Animals↗
PubMed2000

Cardiac troponin T alterations in myocardium and serum of rats after stressful, prolonged intense exercise.

The goal of this study was to determine whether the stress of forced exercise would result in injury to the myocardium. Male rats with 8% of body weight attached to the tail were forced to swim 3.5 h (3.5S), forced to swim 5 h (5S), or pretrained for 8 days and then forced to swim 5 h (T5S). Rats were killed immediately after they swam (0 h PS) and at 3 h (3 h PS), 24 h (24 h PS), and 48 h after they swam (48 h PS). Tissue homogenates of the left ventricle were analyzed by Western blot analysis for cardiac troponin T (cTnT). Serum cTnT was quantified by immunoassay. Results indicated that, in the 3.5S, 5S, and T5S groups, serum cTnT was significantly (P < 0.01) increased at 0 and 3 h PS. The 5S group demonstrated a greater increase in serum cTnT than the 3.5S group (P < 0.01) and the T5S group (P < 0.01) at 0 h PS. Western blot analysis indicated significant decreases (P < 0. 01) in myocardial cTnT in the 5S group only at 0 h PS (P < 0.01) and 3 h PS (P < 0.05). Histological evidence of localized myocyte damage demonstrated by interstitial inflammatory infiltrates consisting of neutrophils, lymphocytes, and histiocytes, as well as vesicular nuclei-enlarged chromatin patterns, was observed in left ventricle specimens from the 5S group at 24 and 48 h PS. Our findings demonstrate that stressful, forced exercise induces alterations in myocardial cTnT and that training before exercise attenuates the exercise-induced heart damage.

Animals↗