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A R Henderson

Publications and source records attributed to A R Henderson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Is determination of creatine kinase-2 after electrophoretic separation accurate?

Since 1991, the Ontario Laboratory Proficiency Testing Program has assessed the analytical performance of creatine kinase (CK; EC 2.7.3.2) isoenzyme-2, using fresh human serum supplemented with purified human CK isoenzymes. In Ontario, the 142 laboratories licensed to analyze CK-2 use a variety of methods: electrophoresis-based, immunoinhibition, and mass assays. During a 1992 survey, duplicate CK-2 samples with different total CK activities showed poorer precision when analyzed after electrophoretic separation than by any other method. A 1993 survey designed to validate these observations conclusively showed that electrophoresis-based assays are subject to a bias proportional to the total CK activity. These survey results were confirmed by studies with selected patients' specimens. We therefore conclude that electrophoresis-based assays may not warrant their reputation as the gold standard for CK isoenzyme measurement.

Creatine Kinase↗
PubMed1993

In vitro effect of elastase and cathepsin G from human neutrophils on creatine kinase and lactate dehydrogenase isoenzymes.

The polymorphonuclear granulocyte, or neutrophil, has been implicated as a mediator of tissue-destructive events because it releases the preformed proteolytic enzymes elastase and cathepsin G, and, as a result of myeloperoxidase action, hypochlorous acid. We show that elastase inactivates and fragments creatine kinase isoenzymes CK-2 and CK-3, and, to a lesser extent, lactate dehydrogenase (LD) isoenzyme LD-1, whereas cathepsin G acts only on CK-2. Both neutrophil enzymes act on LD-3. The course of inactivation was followed by measuring the loss of catalytic activity at 37 degrees C. The evidence for fragmentation was obtained by gel filtration; electrophoresis after sample treatment with sodium dodecyl sulfate and 2-mercaptoethanol was less satisfactory for this purpose. Hypochlorous acid inactivates CK activity by about 75% at concentrations as low as 8 mumol/L and totally at concentrations > 140 mumol/L, whereas LD activity is not affected until concentrations exceed 200 mumol/L. After a myocardial infarction, the number of neutrophils increases; they are triggered and concentrate around damaged myocardial tissue. Our data suggest that neutrophils may inactivate and fragment "cardiac" enzymes released from such damaged tissue.

Cathepsin G↗
PubMed1993

Diagnostic evaluation of creatine kinase-2 mass and creatine kinase-3 and -2 isoform ratios in early diagnosis of acute myocardial infarction.

The diagnostic efficacy of creatine kinase (CK) isoforms (CK-3 and CK-2) was compared with measurement of CK-2 mass concentrations for the early diagnosis of myocardial infarction (MI). Serial serum samples drawn from 76 patients with confirmed MI and 55 non-MI patients were used for determining CK-2 mass concentrations and the MM3/MM1 (CK-3 isoforms) and MB2/MB1 (CK-2 isoforms) ratios. We compared the diagnostic utility of each by receiver-operating-characteristic (ROC) curve and likelihood ratio analyses. Our results indicate that all three tests were ineffective within the first 4 h after the onset of chest pain. All three were most effective at 4-18 h after onset, but both CK-3 and CK-2 isoform ratios were less effective than CK-2 mass concentrations in the next 6-h period (18-24 h). In the critical time between 3 and 6 h, the diagnostic performance of all three was comparable.

Adult↗
PubMed1993

The freckle plot (daily turnaround time chart): a technique for timely and effective quality improvement of test turnaround times.

Test turnaround times are often monitored on a monthly basis. However, such an interval usually means that not all causes for delay in test reporting can be unequivocally identified for institution of remedial action. We have devised a daily chart--the freckle plot--that graphically displays the test turnaround times by laboratory receipt time. Different symbols are used to designate specimens reported within the test's turnaround time limit, those within 10 min beyond that limit, and those well outside the limit. These categories are adjustable to suit different limits of stringency. Freckle plots are produced on a daily basis and can be used to track down causes for test delays. Using the 1-h turnaround time "stat" potassium test as a model, we found 16 causes for test delay, of which 9 were potentially remediable. By applying these remedies, we were able to increase test compliance, in the day shift, from 91.5% (95% confidence interval 88.8%-93.7%) to 97.6% (95% confidence interval 96.4-98.55%), which is significant at P < 10(-7). This daily plot is a useful quality assurance tool, supplementing the more conventional tests used to ensure laboratory quality improvement.

Chemistry, Clinical↗
PubMed1993

Chemistry with confidence: should Clinical Chemistry require confidence intervals for analytical and other data?

Confidence intervals are not commonly provided with analytical or other data reported in Clinical Chemistry although P values are. However, confidence intervals provide an explicit demonstration of the direction and magnitude of uncertainty and are intuitively easy to grasp, unlike P values. It is therefore argued that the Journal should adopt a policy requiring the provision of confidence intervals. Such a policy would improve the statistical rigor of Journal reports.

Chemistry, Clinical↗
PubMed1992

Testing for creatine kinase and creatine kinase-2 in Ontario: reference ranges and assay types.

In 1991, 246 and 136 Ontario laboratories performed total creatine kinase (CK; EC 2.7.3.2) and creatine kinase-2 (CK-2) assays, respectively. A questionnaire mailed to these laboratories requested information about the types of assay used, the origin of their reference ranges, and the source of their instruments and reagents. All laboratories used current test formulations for CK, although seven laboratories did not assay at 37 degrees C. For CK, 69% of all laboratories reported different upper reference limits for men and women (5th-95th percentiles: 160-250 and 115-215 U/L, respectively); 31% reported similar ranges for both sexes. Fifty-six percent derived their own ranges; the remainder used either kit inserts or literature references, and nearly 60% of this latter group claimed to have validated these suggested ranges before use. For 6% of all laboratories, their pediatric ranges were similar to their adult ranges. For CK-2, only 32% used their own reference range; the remainder used kit inserts or literature references, but only 49% of this group validated these ranges before use. Reference limits (5th-95th percentiles) for CK-2 were as follows: activity 6-24 U/L; fraction of CK, 0.022-0.06; and, for mass assays, 5-10 micrograms/L and relative index 0.015-0.04.

Creatine Kinase↗
PubMed1991

Comparison of the diagnostic utility of timed serial (slope) creatine kinase measurements with conventional serum tests in the early diagnosis of myocardial infarction.

We compared the diagnostic utility of recently proposed slope assays for serum creatine kinase and creatine kinase-2 with the optimized decision threshold assays. The former approach has been claimed to be superior to any other single diagnostic technique. We show, by ROC curve and likelihood ratio analyses, that the total creatine kinase slope assay possesses the same diagnostic power, when confidence intervals are used, as the optimized decision threshold assay. Moreover, slope assays of creatine kinase-2 were diagnostically inferior to the optimized decision threshold assays. Indeed, these latter, optimized, assays have the highest likelihood ratios for a positive test result of the available assays, and they should always be used in situations of diagnostic doubt.

Adult↗
PubMed1991

Results of a province-wide quality assurance program assessing the accuracy of cholesterol, triglycerides, and high-density lipoprotein cholesterol measurements and calculated low-density lipoprotein cholesterol in Ontario, using fresh human serum.

To evaluate laboratory performance, eight to 13 samples of fresh human serum from volunteers were sent to 250 laboratories in the Canadian province of Ontario licensed to perform lipid analysis. Fresh human specimens were used because of potential matrix effects with processed materials. We show that on all survey samples, 71% (range, 63% to 82%) of participating laboratories are within +/- 5% of the target cholesterol value and that 93% are within +/- 10%. The goal of the National Cholesterol Education Program for 1992 is total error of no more than +/- 9% for 95% of results. The unblanked triglycerides results show that on all samples 40% (14% to 59%) of participants are within +/- 5% and 68% (range, 31% to 86%) are within +/- 10% of the target value. For triglycerides results from 0.9 to 2.0 mmol/L, 80% or more are within +/- 0.2 mmol/L. Between 2.0 and 3.0 mmol/L, 90% are within +/- 0.3 mmol/L of the target values. For high-density lipoprotein cholesterol, for all samples 35% (range, 24% to 50%) of laboratories are within +/- 5% and 68% (range, 55% to 88%) are within +/- 10%. A range of 80% to 95% of participants are within +/- 0.2 mmol/L of the target values. For calculated low-density lipoprotein cholesterol, 51% and 62% of the laboratories surveyed are within +/- 5%, with 83% and 89% within +/- 10% of the target values. We conclude that the laboratory measurement of lipids is approaching the degree of accuracy and precision required for clinical purposes, and that the use of fresh human serum samples is a viable approach to their proficiency testing.

Blood Chemical Analysis↗
PubMed1991

Potent inhibition of oesophageal metabolism of N-nitrosomethylbenzylamine, an oesophageal carcinogen, by higher alcohols present in alcoholic beverages.

The main cause of oesophageal cancer in western countries is consumption of alcoholic beverages, the degree of risk being much greater for certain spirits than for wine or beer. Risk shows a striking correlation with the content of higher alcohols in the drinks, although the alcohols per se have not been shown to be carcinogenic in experimental animals. To test the concept that higher alcohols modulate the oesophageal carcinogenicity of nitrosamines by altering their metabolism, we studied the effect of certain higher alcohols on the metabolism of N-nitrosomethylbenzylamine by rat oesophageal mucosal and liver microsomes. In oesophagus, the alcohols were 1000 times more inhibitory than ethanol, and in liver 100 times. This suggests that enhancement of carcinogenesis may not result from an effect on nitrosamine metabolism. Higher alcohols could act by increasing the rate of replication of cells already initiated for malignancy by previous exposure to nitrosamines. Intubation of 2-methylbutanol produces a very much greater increase in oesophageal basal-cell proliferation than does ethanol.

Alcoholic Beverages↗
PubMed1990

Proficiency testing for creatine kinase isoenzyme CK-2 (CK-MB) in Ontario.

Three surveys of the measurement and interpretation of creatine kinase (CK; EC 2.7.3.2) isoenzyme 2 (CK-MB) were conducted in Ontario, Canada, in 1989. Of the clinical laboratories participating, 66% used immunological methods and 24% used electrophoretic methods. Although reference ranges and interpretative routines varied widely, 95% of the laboratories reported correct interpretations for 10 of the 15 vials tested. The only major problems occurred with samples with very low total CK activity. Within-survey duplicate results compared well, and 89% of the laboratories had consistent between-survey results, even for specimens with low total CK activity. Errors were proportional to the frequency of use of the different analytical methods. The lyophilized testing material gave higher results with methods for measuring the mass of CK-2, suggesting that the material contained inactive but immunologically intact CK-2. The surveys indicate that laboratories should review their protocols for measuring CK-2 when only a single sample from the patient is available.

Creatine Kinase↗
PubMed1990

Time-related changes in the diagnostic utility of total lactate dehydrogenase, lactate dehydrogenase isoenzyme-1, and two lactate dehydrogenase isoenzyme-1 ratios in serum after myocardial infarction.

Using receiver-operating characteristic (ROC) curve and likelihood ratio analysis, we examined the diagnostic utility of total lactate dehydrogenase (LD; EC 1.1.1.27) activity (I). LD isoenzyme-1 activity (II), and the LD-1 percentage of total LD activity (III), LD-1 LD-2 (IV), and LD-1/LD-4 (V) in 347 persons admitted to the Cardiac Care Unit (of whom 173 were subsequently proven to have had myocardial infarction). Blood was sampled from these subjects at about 6-h intervals for up to 96 h from the onset of chest pain. Defining an "effective" test as one having an area under the ROC curve of greater than or equal to 0.9, we determined the ranked utility (greatest to least) of these tests as V = IV greater than III greater than II greater than I. Tests III, IV, and V had by this criterion, diagnostic effectiveness equivalent to measurements of creatine kinase-2 in serum but in samples obtained at later time intervals. The decision thresholds for both high (constant) test sensitivity and specificity varied with time, to differing extents, over the entire 96-h period, a finding with important diagnostic implications. We document positive and negative likelihood ratio values for each of these tests throughout the entire period of study.

Adult↗
PubMed1989

A computer program to determine diagnostic decision thresholds and likelihood ratios illustrated with aspartate aminotransferase activities after a myocardial infarction.

We describe an enhancement of our earlier computer program which allows calculation of decision thresholds, sensitivity and specificity, and likelihood ratios of negative and positive test results for any chosen value of sensitivity or specificity. The program will also plot continuous receiver operating characteristic and decision level curves which permit examination of the contours created by using all the available data. We illustrate the value of these routines by showing that the sensitivity and specificity of serum aspartate aminotransferase changes during the course of a myocardial infarction.

Aspartate Aminotransferases↗
PubMed1989

The effect of nonionic radiographic contrast medium on serum electrolytes and proteins during intravenous urography.

A prospective study was done on 20 adult patients to determine changes in the serum electrolytes and proteins produced by bolus administration of 100 ml of the nonionic contrast medium iohexol (Omnipaque 300) for intravenous urography. Blood samples were taken for analysis before injection and at five and 30 minutes after. Statistically significant decreases in serum sodium, potassium, total protein, albumin, calcium, and phosphate were noted at five minutes post-injection (p less than 0.001). The mean percentage decreases were sodium 2.4%, potassium 5.1%, total protein 13.7%, albumin 14.2%, calcium 8.6%, and phosphate 5.3%. These values were significantly decreased after 30 minutes (p less than 0.001) except for the serum potassium concentration which had almost returned to baseline level. The changes in sodium, potassium, and phosphate are small and thought to be secondary to hemodilution due to the osmolality of the contrast. The changes in total protein, albumin, and calcium were much greater and difficult to explain. Although we found significant changes in serum biochemistry and proteins, these did not appear to cause clinical abnormalities in this group of patients.

Adult↗
PubMed1989

Re-evaluation of the diagnostic utility of serum total creatine kinase and creatine kinase-2 in myocardial infarction.

The diagnostic utility of total creatine kinase activity (I), creatine kinase-2 isoenzyme activity (II), and II as a percentage of I, was examined by receiver-operating characteristic curve and likelihood ratio (LR) analyses in 310 persons admitted to the Coronary Care Unit (151 proven cases of myocardial infarction and 159 non-myocardial infarction controls), from whom blood was sampled at 6-h intervals for 48 h after the onset of chest pain. I was ineffective either as a "rule-in" or as a "rule-out" test within the first 6 h of the onset of chest pain; thereafter, it was an effective test. II was the most effective test during the entire 48-h period. III was more effective than I in the first 24-h period, but was less effective than I during the next 24-h period. The decision threshold for high test sensitivities varies with time over the entire 48-h period, but remains constant for high test specificities. It is essential to tabulate the LR(+) and LR(-) values for both test sensitivity and specificity at constant values to determine the utility of each test at each time interval for respectively ruling out or ruling in a diagnosis of myocardial infarction.

Creatine Kinase↗
PubMed1989

Use of purified lyophilized human lactate dehydrogenase isoenzyme 5 in a study of measuring lactate dehydrogenase activity.

We examined the stability of human lactate dehydrogenase (EC 1.1.1.27) isoenzyme 5--purified to a specific activity of about 400 kU/g--when lyophilized in a buffered, stabilized matrix of bovine albumin. This isoenzyme was prepared with a final activity of about 500 U/L and stored at -20, 4, 20, 37, and 56 degrees C for as long as six months. This isoenzyme decayed with approximate first-order kinetics, with an estimated half-life at -20 degrees C of about 475 years. Stability of reconstituted samples stored at 20 or 4 degrees C was poor, suggesting that the reconstituted material should be used without delay; material stored at -20 degrees C showed excellent stability for 15 days. We propose that such preparations might be further investigated as standards for use in electrophoresis of lactate dehydrogenase isoenzymes.

Enzyme Stability↗