The content and distribution of troponin I, troponin T, myoglobin, and alpha-hydroxybutyric acid dehydrogenase in the human heart.

We studied the content and distribution of heart-specific markers troponin I and troponin T in relation to conventional non-heart specific myoglobin and alpha-hydroxybutyric acid dehydrogenase (HBD) in the hearts of 34 patients who died of various causes. Tissue was obtained from the right and left ventricles, the interventricular septum, and the right and left atria. We found significant differences in the contents expressed per gram wet weight tissue in the right and left ventricles for troponin I (by 1 of the 2 methods used), troponin T, myoglobin, and HBD and no differences per gram of protein. The biochemical contents per gram wet weight tissue and per gram protein were significantly lower in the right and left atria for all studied markers compared with the right and left ventricles. No significant differences were found in biochemical contents between the right and left atria. These findings imply that estimation of myocardial damage through cardiac markers levels in serum depends on the site of injury (atrium or ventricle). Comparison of myocardial injury among individuals using marker levels in serum is not reliable because of the varied ranges of markers in tissue contents.

Monitoring of impending myocardial damage after pleuropneumonectomy and intraoperative photodynamic therapy for malignant pleural mesothelioma using biochemical markers.

In five patients who were treated for malignant pleural mesothelioma (MPM) with pleuropneumonectomy and intraoperative photodynamic therapy (IPDT), impending myocardial damage was monitored using ECG, the classical biochemical markers (creatine kinase [CK], total activity; CKMB, mass; and myoglobin), and the new cardiac markers troponin I (cTnI) and troponin T (cTnT). In the peroperative and postoperative period all classical markers were elevated, in contrast to cTnI and cTnT, because of the concomitant skeletal muscle damage. Sequential electrocardiogram monitoring showed no signs of myocardial damage. From this study in patients with MPM treated with pleuropneumonectomy and IPDT it can be concluded that measurement of cTnI and cTnT for the detection of myocardial damage is more suitable than measurement of the classical markers.

Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia.

The standard therapy for patients with fever and chemotherapy-related neutropenia is hospitalization and infusion of broad-spectrum antibiotics. Early discharge of a defined group of patients at low risk for septicaemia would be of great advantage for these patients. In this study plasma interleukin-8 (IL-8) and interleukin-6 (IL-6) levels measured at start of fever (n = 72) could define a low-risk group of febrile patients with neutropenia due to chemotherapy. For this purpose we collected and analysed data on 72 fever episodes from 53 patients with chemotherapy-related neutropenia, aged between 1 and 66 years. Of the 72 episodes, 18 were classified as bacteraemia and/or clinical sepsis (sepsis group). The IL-6 and IL-8 plasma concentration were significantly increased in patients with chemotherapy-related neutropenia and fever due to bacteraemia versus fever of non-bacterial origin (P = 0.043 and P = 0.022 respectively). Logistic regression analysis, with sepsis as the outcome variable, revealed significant effects of age combined with either IL-6 or IL-8. Sepsis occurrence was lowest for patients <16 years and highest in patients between 16 and 50 years, and was higher in patients with increased IL-6 (P = 0.032) or IL-8 (P = 0.049). No significant effect of leucocyte count, C-reactive protein, sex or underlying malignancy at presentation was detected. The plasma IL-6 and IL-8 levels were fairly strongly correlated (Pearson r = 0.62). Using a cut-off value with 100% sensitivity, both IL-8 and IL-6 could define a low-risk group of neutropenic patients of 28% (CI 15-40%) at the start of the febrile period. Intervention studies are warranted to confirm this result and to investigate whether an early discharge based on IL-8 or IL-6 measurement is safe, increases the quality of life, and results in cost savings.

Troponin I, troponin T, CKMB-activity and CKMB-mass as markers for the detection of myocardial contusion in patients who experienced blunt trauma.

Myocardial contusion is an infrequent, but sometimes serious complication in patients who experienced deceleration (blunt) trauma. We investigated the assessment of the new cardiac markers troponin I (cTnI) and troponin T (cTnT) in relation to the conventional CKMB-activity, the CKMB-activity/CK-total ratio, CKMB-mass and the CKMB-mass/CK-total ratio for the detection of myocardial contusion in 89 patients with blunt trauma (38 patients with thoracic injuries and 51 patients without thoracic injuries). All parameters were analysed at admission (t1) and 24 h after admission (t2). For the patients with thoracic injuries, at t1 cTnI was elevated in three, and cTnT in four patients; at t2 both cTnI and cTnT were elevated in nine patients. At t1, eighteen to thirty patients had increased levels of the conventional parameters; at t2 this was true for six to thirty-five patients. For the patients without thoracic injuries all cTnI and cTnT levels were within the reference ranges at t1. At t2 one patient, who experienced an acute myocardial infarction, had elevated cTnI and cTnT levels. At t1, five to thirty-five patients had increased levels of the conventional parameters; at t2 this was true for four to forty-two patients. From this study we conclude that the conventional parameters are not useful for the detection of myocardial contusion in patients experiencing blunt trauma. The parameters cTnI and cTnT are equally accurate and more reliable for the selection of patients who require intensive cardiac monitoring. If at admission the cTnI or the cTnT levels are within the reference ranges, a second analysis after admission is necessary to reach a reliable conclusion concerning myocardial contusion as a result of trauma on basis of the troponin levels.

[The elevation of serum creatine kinase-MB level in trauma patients: misleading impression of myocardial damage]. / Verhoging van de creatinekinase-MB-waarde in serum van traumapatiënten: ten onrechte vermoeden van hartspiercelschade.

OBJECTIVE: To determine the frequency of increase of serum values, not of cardiac origin, of creatine kinase-MB (CK-MB) in trauma patients. DESIGN: Prospective. SETTING: University Hospital, Groningen, the Netherlands. METHODS: 51 trauma patients without chest injury (without myocardial contusion) but with (among others) soft tissue injuries, were included. At admission (time point t1) an ECG and chest X-ray were made and blood was collected for measurement of CK total, CK-MB activity and CK-MB mass. If the CK-MB activity/CK total fraction exceeded 3%, CK electrophoresis was performed. Blood analysis was repeated after 24 hours (t2). RESULTS: CK-MB activity was elevated in 27 patients (53%) at t1 and in 3 (6%) at t2. The fraction CK-MB activity/CK total exceeded 3% in 96% and 33% of these patients at t1 and t2, respectively. In all these cases a CK-BB band was detected by electrophoresis (CK-BB interferes with the CK-MB activity measurement). CK-MB mass was elevated in 11 patients (22%) at t1 and in 19 (37%) at t2. CONCLUSION: CK-MB was frequently elevated in trauma patients owing to skeletal muscle damage and to interference with CK-MB activity measurements. For the detection of myocardial damage in trauma patients, CK-MB measurements are of little use.

Analytical aspects of the automated CKMB1,2 and CKMM1,2,3 isoform determination and its relation to other biochemical markers.

The automated (CK)MB1,2/MM1,2,3 isoform measurement, based on electrophoresis, has been simplified to the point that it has become possible to perform this analysis on a 24-h routine basis. We studied analytical aspects of this analysis and its clinical relevance in relation to other biochemical markers (CK total, CKMB activity, CKMB mass, myoglobin, Troponin I and Troponin T) in patients with acute myocardial infarction (AMI), patients with unstable angina pectoris (UAP), and healthy donors. Furthermore, the additional significance of the analysis was evaluated in patients with clinically unexpected, raised CKMB/CK total activities. The storage of serum at 4 degrees C does not influence the MB2/MB1 ratios, whereas storage at 20 degrees C changes them significantly. MM3/MM1 and normal MB2/MB1 ratios show lower coefficients of variation than increased MB2/MB1 ratios. Between 2 and 30 h after myocardial tissue damage, AMI patients showed a characteristic change in CK isoform patterns. At a mean time of 3.6 h after the onset of symptoms we found raised MB2/MB1 ratios in 94% of these patients. With the information of the CK isoform analysis unexpected abnormal CK activities could explained by CK macro enzymes (Ig-bound and mitochondrial), insufficient CK clearance capacity, enzyme activities 4 h after (re-)infarction and raised CK activity 15 h after skeletal muscle damage. We conclude that the CK isoforms are relatively simply to assess; they are adequate tools with which to indicate the CK kinetics over a period lasting between 2 and 30 h after tissue damage with a single blood sample and a single analysis; the CK isoform analysis has additional value in explaining inappropriate CKMB/CK total activities, and the MB2/MB1 ratios show to be one of the best early parameters for discriminating patients with AMI on admission to hospital.

Implications of automated creatine kinase (CK)-MM1,2,3/CK-MB1,2 isoform analysis as an early marker for the detection of myocardial tissue damage.

Measurement of creatine kinase (CK) isoforms enables the clinician to detect myocardial tissue damage at an early stage after myocardial infarction. According to the manufacturer's specifications, it should be possible to perform CK isoform analysis automatically using the new Cardio Rep analyser. In order to investigate the suitability of this new analyser we measured the CK MM1-3, and CK MB1 and 2 isoform patterns, firstly in 30 patients with acute myocardial infarction (AMI), for whom total CK and CK-MB levels were ordered, and secondly in 23 patients with chest pain suspected as having AMI (n = 11) or with unstable angina pectoris (UAP) (n = 12). The total time for analysis, including 5 min pre- and 10 min post-analyser run time, was found to be 40 min. For elevated MB2/MB1 ratios there is a discrepancy between the MB2/MB1 ratios determined from the densitometric scans concerning the surface and the peak height ratios. The MB2/MB1 ratios of the studied AMI patients exceeded the upper reference limits approximately 2 h after the onset of symptoms, whereas the CK-MB and total CK levels increased after about 6 h. The MB2/MB1 ratios from the patients with UAP were either below the detection limit or these patients could be discriminated from patients with AMI when low CK-MB and total CK levels were considered in conjunction. From our results we conclude that assessment of CK isoforms can be performed relatively simply with the new analyser within 40 min. However, for reliable calculation of the MB2/MB1 ratios, the curve monitoring of the MB2-MB1 densitometric scans should be improved. The CK isoforms are useful as an early marker for AMI as their reference interval is already exceeded approximately 2 h after an AMI. Moreover, CK isoform analysis might prove to be useful in discriminating at an early stage between AMI and other causes of chest pain. This could decrease the number of patients with a false-positive diagnosis admitted to coronary care units, resulting in a reduction of costs.

The determination of reference values for hematologic parameters using results obtained from patient populations.

Reference values for hematologic parameters are determined using data from patient populations of a whole year. As a consequence, the authors are not dependent on a limited selected population and can determine reference values for all age and sex groups. It turns out that from the possible compilation technics the gamma distribution gives the best fit. If the results are compared with values stated in the literature, it is remarkable that the total number of leukocytes for men older than 50 years is higher than for women; both the absolute and relative amount of monocytes and eosinophilic granulocytes are higher for men than for women. The platelets are lower for men than for women from the age of 15 years on.