Sampling from a skewed population distribution as exemplified by estimation of the creatine kinase upper reference limit.

1984 ◽  
Vol 30 (1) ◽  
pp. 18-23 ◽  
Author(s):  
W G Miller ◽  
V M Chinchilli ◽  
H D Gruemer ◽  
W E Nance
Keyword(s):  
Mathematical Model ◽  
Creatine Kinase ◽  
Adult Female ◽  
Parametric Analysis ◽  
Population Distribution ◽  
Male And Female ◽  
Reference Limit ◽  
Mathematical Formulas ◽  
Upper Reference Limit ◽  
Larger Sample

Abstract Creatine kinase (EC 2.7.3.2) was measured in sera from 580 females, ages 1-77 years, and 550 males, ages 1-63 years. The distribution of results for male and female groups shows pronounced skewing toward higher values. The observed distribution of results could not be described by any of six mathematical formulas for skewed distributions, an indication of the unsuitability of such formulas to transform these data for parametric analysis. The range of 97.5 percentile estimates produced by six independent samples of 100, 200, and 400 observations randomly selected from a mathematical model defined by the adult female distribution showed progressive narrowing from the 150-380 U/L interval for the samples of 100 observations to 200-265 U/L for the samples of 400 observations; no further improvement was seen when 800 observations were used. The samples of 100 and 200 observations contained extreme value points that might appear as "outliers" but were shown to be valid members of the population distribution when larger sample sizes were collected.

Clinical and analytical evaluation of kits for measurement of creatine kinase isoenzyme MB.

1986 ◽  
Vol 32 (1) ◽  
pp. 186-191 ◽  
Author(s):  
T R Koch ◽  
U J Mehta ◽  
H C Nipper
Keyword(s):  
Creatine Kinase ◽  
Clinical Performance ◽  
Reference Population ◽  
Reference Ranges ◽  
Diagnostic Specificity ◽  
Electrophoretic Method ◽  
Reference Limit ◽  
Coronary Care ◽  
Upper Reference Limit ◽  
Creatine Kinase Isoenzyme Mb

Abstract We studied the analytical and clinical performance of six methods for creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB): three immunoassays (Behring, Hybritech, and International Immunoassay Labs); one immunoinhibition assay (Roche); one immunoinhibition/column method (Du Pont); and one electrophoretic method (Beckman). Between-day precision for all kits was poor at the upper reference limit. All methods gave results linearly related to CK-MB concentration and all were free from CK-MM, CK-BB, and adenylate kinase interference. Only the Du Pont method was adversely affected by atypical isoenzymes. For diagnosis of acute myocardial infarction in a coronary care population (n = 40; prevalence = 45%), all methods were approximately 95% efficient, when appropriate reference criteria were used. Some manufacturers fail to provide data for an appropriate (acutely ill, non-infarct) reference population; decreased diagnostic specificity may result from use of reference ranges based on results for healthy subjects. Expression of CK-MB as a percent of total CK degrades efficiency unless total CK is markedly increased.

A sensitive bioluminescent immunoinhibition test for CK-B subunit activity and a CK-MB specific ELISA compared: correlation with agarose electrophoresis and influence of CK-isoenzyme profile on results.

1988 ◽  
Vol 34 (7) ◽  
pp. 1474-1478 ◽  
Author(s):  
F Gorus ◽  
V Claessens ◽  
P Goubert ◽  
M Laureys
Keyword(s):  
Creatine Kinase ◽  
Regression Analysis ◽  
Linear Regression Analysis ◽  
Test Results ◽  
Electrophoretic Method ◽  
Reference Limit ◽  
B Subunit ◽  
Highly Sensitive ◽  
Agarose Electrophoresis ◽  
Upper Reference Limit

Abstract Searching for alternatives to the imprecise spectrophotometric tests for low-concentration creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB), we investigated the analytical performance of two potentially superior approaches--a bioluminescent immunoinhibition assay (I, LKB-Wallac) and an ELISA (enzyme-labeled immunosorbent assay) technique (II, Hybritech)--in comparison with an electrophoretic method (III, Beckman). Only I showed good between-day precision (CV 8.3%) at the upper reference limit, allowing reproducible assay of CK-B subunit activity down to at least 3 U/L. In conditions where CK isoenzyme assays remained unaffected by CK-MM concentrations, test results were proportional to the amount of CK-MB in the sample up to at least 50 U/L for I, 120 micrograms/L for II, and 100 U/L for III (r greater than 0.998 by linear regression analysis). For CK-MB-positive samples, the data by I correlated more closely with values by III (n = 24; r = 0.994) than did results by II (n = 15; r = 0.909), but both methods were equally effective in discriminating between samples with or without electrophoretically supranormal CK-MB activity (93% sensitivity). II was entirely CK-MB specific, whereas CK-B activity by I was consistently (18/18) increased in CK-MB-negative samples containing CK-BB (n = 6; r = 0.996) or macro CK, types 1 or 2 (n = 12; r = 0.930). I is highly sensitive for screening for increased non-MM CK activity, the nature of which should be subsequently clarified by electrophoresis.

Mass concentration and activity concentration of creatine kinase isoenzyme MB compared in serum after acute myocardial infarction

1990 ◽  
Vol 36 (1) ◽  
pp. 149-153 ◽  
Author(s):  
J R Delanghe ◽  
A M De Mol ◽  
M L De Buyzere ◽  
I K De Scheerder ◽  
R J Wieme
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Creatine Kinase ◽  
Catalytic Activity ◽  
Conformational Changes ◽  
Mass Concentration ◽  
Activity Concentration ◽  
Steady Increase ◽  
Reference Limit ◽  
Upper Reference Limit

Abstract We compared three current methods (immunoinhibition, "Isomune-CK" immunoprecipitation, and the Tandem-E CKMB II immunoenzymometric assay) for determination of creatine kinase (CK; EC 2.7.3.2) isoenzyme MB in serum. Although results inter-correlated well, the immunoinhibition assay gave higher activity values. Atypical CK forms did not interfere with the immunoprecipitation and immunoenzymometric methods. In acute myocardial infarction the catalytic properties of CK decreased with the enzyme's age, as reflected by a steady increase in activation energy of the catalyzed reaction. In septicemia patients with very low CK and CK-MB catalytic activity, mean CK-MB mass concentration exceeded the upper reference limit, suggesting an increased rate of loss of activity concentration in these patients' sera. Because of the assay's lesser susceptibility to conformational changes at the active site of the enzyme, we suggest that measurement of CK-MB mass concentration is better suited for infarct sizing than measurement of catalytic activity.

Measurement of Serum Troponin T, Creatine Kinase MB Isoenzyme, and Total Creatine Kinase following Arduous Physical Training

1995 ◽  
Vol 32 (5) ◽  
pp. 450-453 ◽  
Author(s):  
Paul O Collinson ◽  
Henry A Chandler ◽  
Peter J Stubbs ◽  
David S Moseley ◽  
David Lewis ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Physical Training ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Myocardial Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cardiac Troponin T ◽  
Reference Limit ◽  
Creatine Kinase Mb ◽  
Upper Reference Limit

We have compared measurement of cardiac troponin T by enzyme linked immunosorbent assay with creatine kinase MB isoenzyme (CK-MB) concentration measurement in 219 Royal Marine commandos with no evidence of cardiovascular disease who have elevated creatine kinase (CK) produced by arduous physical training. CK was elevated up to 22.6 times and CK-MB mass up to 6.6 times the upper reference limit. Only two commandos had detectable cardiac troponin T, with neither exceeding the upper reference limit of 0.2 μg/L. At decision thresholds optimized for diagnosis of acute myocardial infarction in previous published work, 58.3% of the total CK activity, 13.8% of the CK-MB concentration/CK activity ratio and 1.6% of CK-MB concentration measurements showed elevated values but no elevations in cardiac troponin T occurred. Cardiac troponin T is currently the investigation of choice for the differential diagnosis of patients with an elevated CK due to skeletal muscle trauma to exclude myocardial damage.

Analytical evaluation of a sensitive enzyme immunoassay for determinations of creatine kinase isoenzyme MB

1990 ◽  
Vol 36 (8) ◽  
pp. 1502-1505 ◽  
Author(s):  
P J Jørgensen ◽  
M Hørder ◽  
J Selmer ◽  
H E Bøtker
Keyword(s):  
Myocardial Infarction ◽  
Creatine Kinase ◽  
Solid Phase ◽  
Signal To Noise Ratio ◽  
Myocardial Damage ◽  
Reference Interval ◽  
Reference Limit ◽  
B Subunit ◽  
Myocardial Diseases ◽  
Upper Reference Limit

Abstract We have evaluated a new sensitive immunometric assay for the determination of creatine kinase (CK; EC 2.7.3.2) MB isoenzyme (NovoClone CK-MB), involving an enzyme label and two monoclonal antibodies directed against the B subunit and the M subunit, respectively. The anti-CK-B antibodies are bound to the solid phase. The assay was modified to be extremely sensitive and thus to measure the concentration range below and close to the cutoff value used for the diagnosis of myocardial infarction. A reference interval of 0-6 micrograms/L was found for 315 outpatients without myocardial diseases (132 men and 183 women); the overall median of the log-gaussian distribution was 1.91 micrograms/L (2.03 and 1.79 micrograms/L for men and women, respectively). Total and within-assay imprecision (CV) was less than 6% at the upper reference limit. The detection limit was 0.1 microgram/L. The assay provides a favorable signal-to-noise ratio: the calibrators 0.0, 2.0, and 30.0 micrograms/L give absorbances at 492 nm of 0.040, 0.140, and 1.600 A. respectively. We conclude that the assay provides biochemical identification of individuals with myocardial damage but without myocardial infarction.

scholarly journals Increased canine pancreatic lipase immunoreactivity (cPLI) and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) lipase in dogs with evidence of portal hypertension and normal pancreatic histology: a pilot study

2021 ◽  
pp. 104063872110039
Author(s):  
Gonçalo Serrano ◽  
Dominique Paepe ◽  
Tim Williams ◽  
Penny Watson
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Pilot Study ◽  
Pancreatic Lipase ◽  
Glutaric Acid ◽  
Inclusion Criteria ◽  
Reference Limit ◽  
Clinical Presentations ◽  
Upper Reference Limit

The clinical presentations of both liver disease and pancreatitis are nonspecific and overlapping, which may cause difficulty in diagnosis. In our retrospective pilot study, we assessed whether dogs with evidence of portal hypertension and absence of pancreatitis on pancreatic histology have increases in canine pancreatic lipase immunoreactivity (cPLI) and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) lipase. We included dogs that had been presented between 2008 and 2019 if they had normal pancreatic histology, histologically confirmed hepatopathy, and if canine pancreas-specific lipase (Spec cPL; Idexx) or DGGR lipase had been measured. Only dogs with portal hypertension were included. Six dogs fulfilled the inclusion criteria. Four of 6 and 2 of 6 dogs had Spec cPL and DGGR lipase exceeding the upper reference limit, respectively. From the 4 dogs with increased Spec cPL, 2 had concentrations of 200–400 µg/L and 2 had concentrations ≥ 400 µg/L. Our results suggest that canine portal hypertension might lead to increased Spec cPL and DGGR lipase values in the absence of pancreatitis on histology. Until more evidence in a larger number of dogs with portal hypertension is available, both tests should be interpreted cautiously in the presence of portal hypertension.

Neuroblastoma—When are Urinary Catecholamines and Their Metabolites ‘Normal’?

1988 ◽  
Vol 25 (6) ◽  
pp. 620-626 ◽  
Author(s):  
D J Worthington ◽  
E M Hammond ◽  
B B Eldeeb ◽  
A Green ◽  
G M Addison ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
The Other ◽  
Published Data ◽  
Single Test ◽  
Creatinine Concentration ◽  
Urinary Catecholamines ◽  
Clinical Sensitivity ◽  
Reference Limit ◽  
Upper Reference Limit ◽  
The Individual

The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.

scholarly journals Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy

2018 ◽  
Vol 64 (9) ◽  
pp. 1370-1379 ◽  
Author(s):  
Peder L Myhre ◽  
Torbjørn Omland ◽  
Sebastian I Sarvari ◽  
Heikki Ukkonen ◽  
Frank Rademakers ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Wall Motion ◽  
Troponin T ◽  
Left Ventricular ◽  
Reference Limit ◽  
Lv Mass ◽  
Lv Remodeling ◽  
Perfusion Defects ◽  
Stable Cad ◽  
Upper Reference Limit

Abstract BACKGROUND Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8–11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

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