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Biomedical subjects

A R Henderson

Publications and source records attributed to A R Henderson.

At least 19 recordsLinked to original sources
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↗
PubMed1979

Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine and methyl methanesulphonate on liver regenerating after partial hepatectomy. IV. Effect on methylase-mediated methylation of DNA.

The possibility that carcinogens may affect methylase-mediated methylation of replicating DNA was investigated. A system eminently suitable for this purpose is liver regenerating after partial hepatectomy, as one injection of dimethylnitrosamine (DMN) given during the ensuing period of increased DNA synthesis induces hepatocellular carcinoma. Methylation of DNA by DNA methylase normally occurs only in proportion to DNA synthesis. Therefore simultaneous measurements were made of synthesis (incorporation of [14C]adenine into DNA adenine, or of d[5-3H]cytidine into DNA cytosine), and of methylation (incorporation of [methyl-3H]methionine into 5-methylcytosine of DNA) in liver regenerating after partial hepatectomy. After treatment with DMN, the ratio of methylation: synthesis remained within the normal range. Methyl methanesulphonate (MMS), a compound which damages DNA in regenerating liver in a similar but not identical way to DMN and which does not induce tumors in liver even when given after partial hepatectomy, caused an increase in methylation in relation to synthesis. These experiments therefore do not support the view that altered DNA methylase activity is involved in carcinogenesis.

Animals↗
PubMed1979

The priority test request form: a method for improving communication between the physician and the Emergency Clinical Biochemistry Laboratory.

Two forms--a priority test request form and a telephone results form--provide improved communication between the physician and the emergency laboratory of the Clinical Biochemistry Department. The priority test request form contains a list of available tests and it allows the physician to tell the laboratory exactly when emergency test results are required. The telephone results form ensures that the physician will receive a report, by telephone, of a test result although it may not be an urgent test. This allows a greater control of work flow, both routine and emergency, through the laboratory.

Biochemical Phenomena↗
PubMed1979

Thin-layer agarose electrophoresis of lactate dehydrogenase isoenzymes in serum: a note on the method of reporting and on the lactate dehydrogenase isoenzyme-1/isoenzyme-2 ratio in acute myocardial infarction.

We assessed the clinical efficacy of a thin-layer agarose electrophoresis assay for lactate dehydrogenase isoenzyme estimation in the diagnosis of acute myocardial infarction. From a population of 228 patients admitted to the Coronary Care Unit with suspected acute myocardial infarction, all 101 positive cases (confirmed by clinical presentation and electrocardiographic changes) were correctly identified with lactate dehydrogenase isoenzyme-1 percentage of total activity above the reference range and with a lactate dehydrogenase isoenzyme-1/isoenzyme-2 ratio of 0.76 or above. This ratio was between 0.45 and 0.74 for 250 healthy subjects. No falsely negative, but 12 falsely positive results were obtained from this Coronary Care Unit population, to give a sensitivity of 100% and a specificity of 90.5% for the ratio test.

Clinical Enzyme Tests↗
PubMed1979

Interaction between human IgG and human creatine kinase isoenzyme-1 in serum: a route for the intravascular catabolism of creatine kinase-1?

In vitro incubation, at 37 degrees C, of human creatine kinase isoenzyme-1 (isoenzyme BB) and human immunoglobulin G in a buffer results in the formation of a complex of high relative molecular mass (Mr approximately 825,000), which contains both proteins. This complex also forms in vitro if creatine kinase isoenzyme-1 is incubated with fresh human serum. The creatine kinase activity of the complex obtained from either incubation is extremely labile, even in the presence of a chelating agent and a thioglycerol. We present evidence for the existence of this complex in the sera of patients who have detectable serum creatine kinase isoenzyme-1 activity. Sera with high activities of creatine kinase isoenzyme-2 do not appear to have this complex. We therefore speculate that complexing of creatine kinase isoenzyme-1 with serum immunoglobulin G may be a pathway of enzyme degradation.

Creatine Kinase↗