Stacey A.A. Honda

Evaluation of Human Serum Albumin Cobalt Binding Assay for the Assessment of Myocardial Ischemia and Myocardial Infarction

BACKGROUND Clinical diagnoses were correlated with results of a Co(II)-albumin binding assay in 167 patients treated at an emergency department of a health maintenance organization. METHODS Patients were evaluated as being nonischemic or potentially ischemic through standard coronary disease indicators [creatine kinase (CK), CK-MB, cardiac troponin I, and electrocardiographic findings] and were tested by a Co(II)-albumin binding assay. Samples were tested anonymously, and the study was double-blinded. The sensitivity and specificity of this assay for the detection of ischemia were evaluated by ROC curve analysis. Known Co(II) binding sites on albumin were analyzed by N-terminal amino acid sequencing. RESULTS The mean absorbance units (ABSU) +/- 2 SD for non-myocardial ischemic and myocardial ischemic individuals measured at 470 nm were 0.43 +/- 0.10 and 0.63 +/- 0.25, respectively (P <0.0001). The area under the ROC curve was 0.95 [95% confidence interval (CI), 0.92-0.99], and at a cutoff value of 0.50 ABSU, sensitivity and specificity were 88% (78-94%) and 94% (86-98%), respectively, suggesting a high distinction between the two groups. When we compared non-acute myocardial infarction (AMI) and AMI ischemic individuals, the area under the ROC curve was 0.66 (95% CI, 0.53-0.79) and was considered a poor discriminator between these two groups. N-Terminal amino acid sequencing data for purified albumin showed normal amino acid residues for six of seven high-ABSU (> or =0.70) individuals and one nonischemic individual tested. However, only one individual with a high ABSU (0.80) had two missing amino acid residues (DA) from the N-terminal region. Clinical diagnosis for this patient did not reveal an ischemic event. CONCLUSIONS The Co(II)-albumin binding test may serve as a useful diagnostic tool in emergency facilities for the assessment of myocardial ischemia. High and low ABSU were associated with myocardial ischemic individuals and non-myocardial ischemic individuals, respectively. However, the Co(II)-albumin binding was a poor discriminator between ischemic individuals with and without MI.

Utility of Serum Fatty Acid Concentrations as a Marker for Acute Myocardial Infarction and Their Potential Role in the Formation of Ischemia-Modified Albumin: A Pilot Study

Myocardial ischemia, which precedes acute myocardial infarction (AMI)1 is associated with changes in human serum albumin (HSA) that result in decreased divalent cobalt ion (Co2+) binding. This reaction the basis of the serum colorimetric Co2+-HSA binding assay, which is an indirect measure of ischemia-modified albumin (IMA). Previously we showed that IMA was a useful diagnostic test for the diagnosis of myocardial ischemia in suspected acute coronary syndromes (ACS) patients (area under the ROC curve 0.95) (1). The IMA values are reversible between ischemic and nonischemic conditions (2). Furthermore, it is known that HSA is the primary binder of fatty acids, commonly known as free fatty acids (FFA), and that plasma concentrations of FFAs are increased during myocardial ischemia owing to a compensatory hyperadrenergic state. Considering these findings, we explored the hypothesis that FFA-induced conformational perturbations of HSA are the basis of the IMA test, and FFAs may themselves serve as a potential marker(s) of myocardial injury. Using pooled serum specimens, we performed an in vitro study to test the effect of physiologically relevant fatty acids on the IMA test. We obtained sera from patients brought to the emergency department at Kaiser Foundation Hospital who initially underwent a diagnostic work-up for ACS. …

Role of cardiac troponin I in the evaluation of myocardial injury

Cardiac troponin I (cTnI) is highly specific for cardiac muscle. In this study, we compared the utility of CK and CK‐MB index versus cTnI in the assessment of myocardial infarction in 155 patients being evaluated for myocardial damage. As a cardiac marker for MI, Troponin I seems to be superior to CK‐MB. In the subset of patients with renal disease, cTnI has definite advantages over CK‐MB. In addition, the use of cTnI has the potential to replace the measurement of lactate dehydrogenase isoenzymes. J. Clin. Lab. Anal. 12:276–279, 1998.

A Healthy Young Man Presenting with Multiple Rib Fractures

A 32-year-old, otherwise healthy man presented initially with right rib and sternal pain after lifting a heavy object. The patient also reported several rib fractures 1 year previously associated with coughing. On examination, the patient had bilateral rib tenderness. Chest x-ray revealed multiple healing fractures of the sixth, seventh, and eighth ribs. A bone scan demonstrated increased uptake in the sternum and bilaterally in the ribs. A complete blood count was normal with the exception of a platelet count of 61 000/uL (reference interval, 130 000–440 000/uL). Alkaline phosphatase, creatinine, and calcium were within reference intervals. Total protein and albumin were 67 g/L (reference interval, 61–79 g/L) and 44 g/L (reference interval, 35–48 g/L), respectively. Ig concentrations were decreased: IgG 6.07 g/L (reference interval, 7.51–15.60 g/L), IgA 0.31 g/L (reference interval, 0.69–2.09 g/L), and IgM 0.10 g/L (reference interval, 0.48–2.74 g/L). We performed serum protein electrophoresis (SPEP)5 and immunofixation using the Sebia Hydrasys®. SPEP showed no monoclonal band in the γ region but an unexplained band in the β region with a reduced γ-globulin concentration of 3.9 g/L (reference interval, 6–14 g/L). Serum immunofixation electrophoresis showed a prominent λ monoclonal band in the β region and hypogammaglobulinemia. Immunofixation studies for IgG, IgA, and IgM were negative for the presence of monoclonal bands. β2-Microglobulin was increased at 3.51 mg/L (reference interval, <1.85 mg/L). Twenty-four-hour urine collection was significant for a total protein of 0.54 g/24 h (reference interval, <0.15 g/24 h); urine protein electrophoresis (UPEP) and immunofixation revealed 2 monoclonal λ light chain bands. ### QUESTIONS TO CONSIDER 1. List the significant and atypical findings in this case. 2. Given the patients SPEP and immunofixation results, what …