116 research outputs found
Laboratoriumgeneeskunde: van evolutie naar revolutie
Oratie uitgesproken door Prof.dr. C.M. Cobbaert bij de aanvaarding van het ambt van hoogleraar in de Klinische Chemie en Laboratoriumgeneeskunde aan de Universiteit Leiden op vrijdag 19 februari 2016Oratie uitgesproken door Prof.dr. C.M. Cobbaert bij de aanvaarding van het ambt van hoogleraar in de Klinische Chemie en Laboratoriumgeneeskunde aan de Universiteit Leiden op vrijdag 19 februari 2016
Regional serum cholesterol differences in Belgium: do genetically determined cardiovascular risk factors contribute?
BACKGROUND: Differences in serum lipid distribution and mortality from
ischaemic heart disease have repeatedly been reported between Belgian
northerners and southerners. We investigated whether serum lipoprotein(a)
(Lp(a)) and apolipoprotein (apo) E polymorphism were involved. METHODS:
Fasting serum lipids, apo A-I and B, and Lp(a) levels were examined in
randomly selected, 20-39 year old Belgian males and females from the north
(Flanders) and the south (Wallonia) of Belgium (N = 900). Apo E phenotype
distribution was investigated in random subsamples from either region (N =
249). RESULTS: Mean serum cholesterol, low density lipoprotein cholesterol
(LDL-c), apo B and triglyceride levels were higher in Walloons compared to
Flemings within each gender, the difference being significant in 30-39
year old males. Average high density lipoprotein cholesterol and apo A-I
levels were significantly lower in 30-39 year old male southerners,
compared to their northern counterparts. Median Lp(a) was 67 mg/l in
northerners and 75 mg/l in southerners (NS). The apo E phenotype
distribution was similar in both regions (chi2 = 7.213; d.f. = 5; P =
0.2053), whereas the average effects of the apo E alleles differed between
the regions. In southerners the epsilon4 effect upon adjusted apo B and
LDL-c levels was approximately+12% and the epsilon2 effect was
approximately-15%; in northerners the epsilon4 and epsilon2 effects were
approximately+5% and approximately-25%, respectively. The apo E
polymorphism did not affect serum Lp(a) levels. CONCLUSIONS: Regional
cholesterol differences between Flemings and Walloons cannot be explained
by differences in serum Lp(a) or apo E phenotype distribution. The less
favourable epsilon2 and epsilon4 effects in southerners compared to
northerners reflect modulation of the apo E gene by particular
environments
Quantifying apolipoprotein(a) in the era of proteoforms and precision medicine
Lipoprotein(a) (Lp(a)) is an independent risk factor in the development of atherosclerotic cardiovascular diseases (ASCVD) and calcific aortic valve disease (CAVD). Lp(a) is an LDL-like particle to which apolipoprotein (a) (apo(a)) is covalently bound. Apo(a) contains a variable number of kringle IV repeats, a kringle V and a protease domain. Serum/plasma Lp(a) concentrations are traditionally expressed as total particle mass in mg/L. Concern has arisen lately as flawed Lp(a) mass tests have masked its clinical utility.The determinants of variability in Lp(a) composition were investigated, including the apo(a) size polymorphism, post-translational modifications -N- and O-glycosylation- and the lipid:protein ratio. Depending on the number of kringle IV-2 repeats, the theoretical protein content of the Lp(a) particle varies between 30 and 46 (w/w) %, which inescapably confounds Lp(a) mass measurements.The authors advocate that reporting of Lp(a) particle concentrations in mass units is metrologically inappropriate and should be abandoned, as it results in systematically biased Lp(a) results. Enabling technology, such as mass spectrometry, allows unequivocal molecular characterization of the apo(a) measurand(s) and accurate quantitation of apo(a) in molar units, unaffected by apo(a) size polymorphism. To guarantee that Lp(a)/apo(a) tests are fit-for-clinical-purpose, basic metrology principles should be implemented upfront during test development.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL
Significance of various parameters derived from biological variability of lipoprotein(a), homocysteine, cysteine, and total antioxidant status
Analytical and biological components of variability and various derived
indices have been determined for lipoprotein(a) [Lp(a)], homocysteine
(Hcy), cysteine (Cys), and total antioxidant status (TAOS) in ostensibly
healthy adult Caucasians and in stable outpatients with an increased serum
Lp(a). In healthy Caucasians, average intraindividual biological CVs (CVb)
were 20.0% for Lp(a), 9.4% for Hcy, 5.9% for Cys, and 2.8% for TAOS, CVbs
being similar in men and women. In the outpatient group, CVbs were
comparable for Hcy, Cys, and TAOS, but significantly lower for Lp(a) (7.5%
vs 20.0%; P <0.0001). Moreover, a significant inverse relation between
both biological and analytical CVs (CVa) and serum Lp(a) concentrations
was demonstrated. We conclude that average CVa and CVb values, and hence
average derived indices, are adequate for Hcy, Cys, and TAOS, whereas
individual values should be used for Lp(a)
The quest for equivalence of test results: the pilgrimage of the Dutch Calibration 2.000 program for metrological traceability
Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL
Should LC-MS/MS be the reference measurement procedure to determine protein concentrations in human samples?
Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL
Survey of total error of precipitation and homogeneous HDL-cholesterol methods and simultaneous evaluation of lyophilized saccharose-containing candidate reference materials for HDL-cholesterol
BACKGROUND: Standardization of HDL-cholesterol is needed for risk
assessment. We assessed for the first time the accuracy of HDL-cholesterol
testing in The Netherlands and evaluated 11 candidate reference materials
(CRMs). METHODS: The total error (TE) of HDL-cholesterol measurements was
assessed in native human sera by 25 Dutch clinical chemistry laboratories.
Concomitantly, the suitability of lyophilized, saccharose-containing CRMs
(n = 11) for HDL-cholesterol was evaluated. RESULTS: In the precipitation
method group, which included 25 laboratories and four methods, the mean
(minimum-maximum) TE was 11.5% (2.7-25.2%), signifying that 18 of 25
laboratories satisfied the TE goal of </=13% issued by the National
Cholesterol Education Program (NCEP). In the homogeneous HDL-cholesterol
method group, which included five laboratories, each performing two
different methods, the mean (minimum-maximum) TE was 9.5% (6.0-17.3%) for
the Boehringer assay and 15.7% (3.3-30.7%) for the Genzyme assay. For the
Boehringer homogeneous assay, one of five laboratories did not meet the TE
criterion, whereas for the Genzyme homogeneous assay, three of five
laboratories exceeded the 13% criterion. The biases on the HDL-cholesterol
values found by various precipitation methods were highly variable in all
CRMs, irrespective of the quality, whereas the biases found by the
homogeneous method from Boehringer were far less than +/-5% for the
highest-quality CRMs (CRMs 4-6). CONCLUSIONS: The NCEP goal was met by 24
of 35 laboratories assessed by use of native human sera. Selectively
pooled, lyophilized CRMs that are cryoprotected with 200 g/L saccharose
have ample potential for use in the standardization of homogeneous
HDL-cholesterol methods
Noninvasive assessment of reperfusion and reocclusion after thrombolysis in acute myocardial infarction.
The clinical significance of ST-segment changes and of the time course of appearance in serum of different cardiac proteins has been reviewed for the diagnosis of coronary reperfusion and reocclusion after thrombolysis. In particular, the value of serial 12-lead electrocardiographic (ECG) studies, of Holter monitoring, and of continuous multilead computer-assisted ECG monitoring is compared. Regarding the serum proteins, the clinical significance of reperfusion indices described so far for serum creatine kinase (CK), its isoenzyme serum creatinine kinase MB, the CK isoforms, and myoglobin is reviewed. Emphasis is placed on (1) the calculation method used for deriving the reperfusion indices; (2) the sensitivity and the specificity of the reperfusion indices; (3) the minimum turn-around time needed to produce the reperfusion indices (depending on the practicability of the analytical and calculation methods and their applicability in an em
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