Gerard T. B. Sanders

Value of Myoglobin, Troponin T, and CK-MBmass in Ruling Out an Acute Myocardial Infarction in the Emergency Room

BACKGROUND Ruling out acute myocardial infarction (AMI) on the basis of rapid assays for cardiac markers will allow early triage of patients and cost-effective use of available coronary care facilities. METHODS AND RESULTS We studied the value of myoglobin, creatine kinase (CK)-MBmass, and troponin T in ruling out an AMI in the emergency room in 309 consecutive patients presenting with chest pain. The gold standard for AMI was the combination of history, ECG, and a typical curve of the CK-MB activity (CK-MBact). Myoglobin was the earliest marker, and its negative predictive value (NPV) was significantly higher than for CK-MBmass and troponin T from 3 to 6 hours after the onset of symptoms (myoglobin versus CK-MBmass, P < .03; myoglobin versus troponin T, P < .01). The NPV of myoglobin reached 89% 4 hours after the onset of symptoms. The NPV of CK-MBmass reached 95% 7 hours after the onset of symptoms. Troponin T was not an early marker for ruling out AMI, and NPV changed over time, together with CK-MBact. The early NPV was higher in a subgroup of patients with a low probability of the presence of AMI for the three markers. Cardiac markers rise earlier in patients with large infarcts than in patients with small infarcts as indicated by the cumulative proportion of the marker above the upper reference limit at each time point (myoglobin, P = .04; CK-MBmass, P = .013; troponin T, P = .016). CONCLUSIONS For ruling out AMI in the emergency room, myoglobin is a better marker than CK-MBmass or troponin T from 3 until 6 hours after the onset of symptoms, but the maximal NPV reaches only 89%. At 7 hours, the NPV of CK-MBmass is 95%. The test characteristics are influenced by the probability of the presence of AMI in the patients studied and by the size of their AMI. Infarct size of AMI patients should be reported in studies evaluating cardiac markers.

Bone-alkaline phosphatase as indicator of bone formation

Bone-alkaline phosphatase was determined in patients at risk of osteoporosis due to treatment with oral corticosteroids, and in patients at risk of increased bone synthesis because of treatment with cyclosporin. Both a significant decrease of bone-alkaline phosphatase during corticosteroid treatment, and a significant increase of bone-alkaline phosphatase during cyclosporin treatment could be demonstrated. It is concluded that bone-alkaline phosphatase is a useful parameter for monitoring changes in bone formation.

Demonstration of the prostatic origin of metastases. An immunohistochemical method for formalin‐fixed embedded tissue

An indirect immunohistochemical technique is described for identification of the prostatic origin of metastases in formalin fixed, paraffin or paraplast embedded material. A rabbit antiserum against the prostate specific acid phosphatase isoenzyme was developed. The method is applicable with or without previous decalcification. In 30 cases of prostatic carcinoma there was only one negative result, and in 20 cases of metastases from prostatic carcinoma positive results were obtained in every instance. All carcinomas (primary focus or metastasis) of non prostatic origin (55) stained negatively with the developed antiserum. The application and possible limitations of the method are discussed.

Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponin T

OBJECTIVES We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (DSE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T. BACKGROUND Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain. The prognostic value of immediate DSE has not been studied in a blinded, prospective fashion. METHODS Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible. Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a standard rule-out protocol and a negative serial troponin T; the occurrence of any new wall motion abnormality was considered positive. Results were kept blinded. End points were cardiac death, myocardial infarction, rehospitalization for unstable angina or revascularization. RESULTS In total, 377 patients were included. There were 2 deaths, 2 myocardial infarctions, 8 rehospitalization for unstable angina, and 10 revascularizations at six-month follow-up. The end points occurred in 8/26 (30.8%) patients with a positive versus 14/351 (4.0%) patients with a negative DSE (odds ratio, 10.7; 95% confidence interval, 4.0 to 28.8; p < 0.0001). By multivariate analysis, DSE remained a predictor of end points (p < 0.0001). CONCLUSIONS A predischarge DSE had important, independent prognostic value in low-risk, troponin negative, chest pain patients.

Magnesium in disease : a review with special emphasis on the serum ionized magnesium

Abstract This review deals with the six main clinical situations related to magnesium or one of its fractions, including ionized magnesium: renal disease, hypertension, preeclampsia, diabetes mellitus, cardiac disease, and the administration of therapeutic drugs. Issues addressed are the physiological role of magnesium, eventual changes in its levels, and how these best can be monitored. In renal disease mostly moderate hypermagnesemia is seen; measuring ionized magnesium offers minimal advantage. In hypertension magnesium might be lowered but its measurement does not seem relevant. In the prediction of severe pre-eclampsia, elevated ionized magnesium concentration may play a role, but no unequivocal picture emerges. Low magnesium in blood may be cause for, or consequence of, diabetes mellitus. No special fraction clearly indicates magnesium deficiency leading to insulin resistance. Cardiac diseases are related to diminished magnesium levels. During myocardial infarction, serum magnesium drops. Total magnesium concentration in cardiac cells can be predicted from levels in sublingual or skeletal muscle cells. Most therapeutic drugs (diuretics, chemotherapeutics, immunosuppressive agents, antibiotics) cause hypomagnesemia due to increased urinary loss. It is concluded that most of the clinical situations studied show hypomagnesemia due to renal loss, with exception of renal disease. Keeping in mind that only 1% of the total body magnesium pool is extracellular, no simple measurement of the real intracellular situation has emerged; measuring ionized magnesium in serum has little added value at present.

Prognostic value of troponin T, myoglobin, and CK-MB mass in patients presenting with chest pain without acute myocardial infarction.

OBJECTIVE: To assess the prognostic value of minor myocardial damage in patients presenting with chest pain without myocardial infarction. DESIGN: The relative risk of suffering a cardiac event in the next six months was assessed in patients with minor myocardial damage assessed by the cardiac markers CK-MB, myoglobin, and troponin T. SETTING: Emergency department of a large university hospital. PATIENTS: In 128 consecutive patients with chest pain, acute myocardial infarction (by WHO criteria) was ruled out; of these, 39 had a rise and fall of one or more markers, indicating minor myocardial damage. The presence of a documented history of coronary artery disease was assessed on admission. RESULTS: 24 patients had a subsequent event (cardiac death, acute myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting) in the next six months. An abnormal troponin T predicted a subsequent event while abnormal CK-MB or myoglobin did not. The relative risk for troponin T was 2.8 (95% confidence interval: 1.0 to 7.9), for myoglobin 1.0 (0.3 to 3.2), and for CK-MB 0.9 (0.2 to 3.4). A documented history of coronary artery disease predicted subsequent events with a relative risk of 3.9 (1.3 to 11.3). CONCLUSIONS: Troponin T was the only marker that predicted future events, but a documented history of coronary artery disease was the best predictor in patients in whom an acute myocardial infarction had been ruled out.

Magnesium levels in critically ill patients. What should we measure

We studied the relation between ionized magnesium, total magnesium, and albumin levels in serum of 115 critically ill patients and the role of extracellular and intracellular magnesium in outcome prediction. Levels of serum total and ionized magnesium, serum albumin, and magnesium in mononuclear blood cells and erythrocytes were measured and the APACHE II score and 1-month mortality recorded. Of all patients, 51.3% had a serum total magnesium concentration below the reference range. In 71% of these hypomagnesemic patients, a normal serum ionized magnesium concentration was measured. None of the patients had an intracellular magnesium concentration below the reference limit. Except for serum total and ionized magnesium, none of the magnesium parameters correlated significantly with each other. A significantly negative correlation was found between serum albumin and the fraction ionized magnesium. There was no association between low extracellular or intracellular magnesium and clinical outcome. The observation of hypomagnesemia in critically ill patients depends on which magnesium fraction is measured. The lack of correlation with clinical outcome suggests hypomagnesemia to be merely an epiphenomenon. Reliable concentrations of serum ionized magnesium can be obtained only by direct measurement and not by calculation from serum total magnesium and albumin.

C-reactive protein and coronary events following percutaneous coronary angioplasty

Abstract Purpose We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. Methods In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. Results The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P P = 0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (± SD) C-reactive protein level (5.8 ± 9.7 mg/L vs. 7.2 ± 12.1 mg/L, P = 0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. Conclusion An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.

Diagnostic accuracy of myoglobin concentration for the early diagnosis of acute myocardial infarction

STUDY OBJECTIVE We evaluated the diagnostic accuracy of myoglobin determination for the early diagnosis of acute myocardial infarction (AMI). METHODS Consecutive patients with chest pain were included in the study. Receiver operating characteristic (ROC) analysis was used to assess optimal timing of blood sampling and cutoff values. RESULTS A total of 309 patients were included, of whom 162 patients had a diagnosis of AMI. ROC analysis revealed that the diagnostic accuracy of myoglobin concentration as indicated by the area under the ROC curve (AUC) increased significantly from 3 (0.89+/-0.026) and 4 hours (0.93+/-0.019) to 5 hours after onset of symptoms (0. 96+/-0.014; P=.0040 and.035, respectively). At 5 hours (the earliest time point with maximal AUC), sensitivity was 87% and specificity was 97% using a myoglobin cutoff value of 90 microg/L. With a myoglobin cutoff value of 50 microg/L, sensitivity was 95% (95% confidence interval 90% to 98%), but specificity was 86% (95% confidence interval 80% to 93%). CONCLUSION Myoglobin has maximal diagnostic accuracy for the diagnosis of AMI at 5 hours after the onset of symptoms, using a cutoff value of 50 microg/L. In combination with the measurement of other biochemical markers, myoglobin determination could be particularly useful for triage of patients with AMI at an early stage.

Determination of uric acid with uricase and peroxidase

A reliable method for the determination of uric acid in plasma or serum is described. The hydrogen peroxidase developed in the uricase reaction is used, together with peroxidase, for the coupling of sulphonated dichlorophenol and 4-aminoantipyine to a red dye. The difference in absorbance at 515 nm before and after addition of uricase is measured. Of the components tested for interference some gave rise to falsely lowered values. Reagents are cheap and the high molecular absorption coefficient of the red dye permits the use of small sample volumes.