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Biomedical subjects

M J McQueen

Publications and source records attributed to M J McQueen.

At least 19 recordsLinked to original sources

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

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

Abnormal enzyme phenotype (E1a E1f): normal response to succinylcholine.

The enzyme serum cholinesterase responsible for the hydrolysis of the muscle relaxant succinylcholine exists in the form of several variants. These may be identified in serum by using substances which inhibit their activity to different degrees. The heterozygote for the atypical and fluoride resistant enzymes (E1a E1f) is one of the phenotypes which has been reported to be sinsitive to succinylcholine. A case is described where succinylcholine given on two separate occasions did not induce apnoea in an individual phenotyped as E1a E1f by at least five methods of inhibition. This is the first reported example of such insensitivity to the drug in this phenotype. Temperature activities for the patient's serum over the range of 20 degrees C to 45 degrees C differed from that of an established E1a E1f phenotype used as a control. There was a progressive inactivation of the control serum at temperatures higher than 35 degrees C, as previously reported for this phenotype. Activity in the serum of the subject of this study did not exhibit the peak activity at 35 degrees C but continued to rise and probably reached a peak between 40 degrees C and 45 degrees C. The significance of these results in the context of current methods of phenotyping is discussed.

Adolescent

Lipoidal bladder concretion: an unusual autopsy finding in acute lymphoblastic leukemia.

The occurrence of a large (2.3 gm.), wax-like, creamy white concretion in the bladder of a 7-year-old girl who died of acute lymphoblastic leukemia is reported. Lipids constituted 40% of the total weight and triglycerides accounted for 95% of the total lipids. The fatty acid composition of the individual lipid classes showed a predominance of saturated fatty acids (75 to 80%). Factors influencing the pathogenesis of the material are discussed. A review of the literature on childhood leukemia showed no reference to such lipid abnormalities and the occurrence of this type of concretion has not been reported previously.

Child, Preschool

Evaluation of an automated immunoassay procedure for apo-LDL for phenotyping type II hyperlipoproteinemia.

Apo-low density lipoproteins were determined by an automated immunoassay procedure on serum samples from 88 normolipidemic individuals and 84 hyperlipoproteinemic subjects, to establish whether this method was useful in the routine detection of type II hyperlipoproteinemia. The results obtained were compared with the cholesterol levels of the same specimens. In subjects with type II hyperlipoproteinemia, the apo low density lipoprotein levels, as well as the ratio of low density lipoprotein cholesterol/apo-low density lipoprotein were higher, as expected, than in normals or in subjects with other types of hyperlipoproteinemia. However, there was considerable overlap in individual values of both these parameters, between patients with type II hyperlipoproteinemia and normals or subjects with other types of hyperlipoproteinemia, suggesting that apo low density lipoprotein levels alone were not sufficiently discriminatory for the laboratory determination of type II hyperlipoproteinemia.

Adult

Succinylcholine sensitivity in a Nova Scotia family.

Succinylcholine apnoea is usually the result of a delay in hydrolysis of the injected muscle relaxant due to the presence of an inherited defect in the enzyme cholinesterase. This report presents a Nova Scotia family in whom several members had "difficulty in breathing" following anaesthesia. Subsequent investigations revealed the presence of several phenotypes of the enzyme cholinesterase including individuals who were homozygous for the atypical cholinesterase genes. The frequency of occurrence and significance of the various phenotypes are discussed, together with their management and recommendations for family screening.

Adolescent

Use of a programmable calculator in processing and interpreting serum cholinesterase phenotypes.

Cholinesterase phenotyping is done at 25 degrees C with use of benzoylcholine as substrate and dibucaine, fluoride, chloride, and succinyldicholine as inhibitors. We wrote a diagnostic program in modified BASIC language for the processing and interpretation of these cholinesterase phenotypes. We used the HP 9830A calculator. The diagnostic aspect of the program uses 646 words, a further 86 words being used to run this program. The traditional and the programmed reporting procedures were duplicated for 296 consecutive patients, with no case of disagreement between the two reporting methods as to the appropriate phenotype. The programmed system requested nine repeat analyses more than did the traditional method. Seven of these were due to the tight limits set in the program for the fluoride inhibitor numbers. These tight limits were set to ensure that there was as limited an overlap as possible between the phenotypes E1uE1u and E1uE1f. The remaining two repeats were due to the restrictions placed on the succinyldicholine inhibitor numbers that would be acceptable before a patient was designated as having the relatively rare phenotype, E1aE1f.

Cholinesterases

True Arrhenius relationships of human lactate dehydrogenase.

The pyruvate and NADH concentrations and the buffer pH which gave maximal activity with LDH isoenzymes derived from human heart and liver tissue were established for the temperatures 25 degrees C, 30 degrees C, 35 degrees C, 37 degrees C,, 40 degrees C, 45 degrees C, and 50 degrees C. The velocities of the LDH isoenzymes using these maximal assay conditions were used to obtain Arrhenius plots, i.e. log initial velocity against inverse absolute temperature. The Arrhenius plots were linear with both isoenzyme preparations up to 45 degrees C. Between 45 degrees C and 50 degrees C it appeared that this linear relationship no longer held, particularly with the liver tissue. When the activation energies were calculated both isoenzyme preparations exhibited several points of inflexion, in each case occuring at the same temperatures. These inflexions represent a change in the reaction kinetics, possibly a conformational change in the enzyme. The results also indicate that the LDH 1 and 2 isoenzymes are more efficient than LDH 4 and 5.

Humans