| 1. |
- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in fluid proteomics
- 2009
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 47:6, s. 724-744
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Forskningsöversikt (refereegranskat)abstract
- The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
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| 2. |
- Ben, Rayana M.C., et al.
(författare)
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Guidelines for sampling, measuring and reporting ionized magnesium in undiluted serum, plasma or blood : International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
- 2005
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 43:5, s. 564-569
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Tidskriftsartikel (refereegranskat)abstract
- All analyzers with ion-selective electrodes for ionized magnesium (iMg) should yield comparable and unbiased results. The prerequisite to achieve this goal is to reach consensus on sampling, measurement and reporting. The recommended guidelines for sampling, measurement and reporting iMg in plasma ("plasma" refers to circulating plasma and the forms in which it is sampled: the plasma phase of anticoagulated whole blood, plasma separated from blood cells, or serum) or blood, referring to the substance concentration of iMg in the calibrants, will provide results for iMg that are approximately 3% greater than its true concentration, and 4% less than its true molality. Binding of magnesium to proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be simultaneously measured to allow adjustment of iMg concentration to pH 7.4. The substance concentration of iMg may be physiologically and consequently clinically more relevant than the substance concentration of total magnesium. © 2005 by Walter de Gruyter.
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| 3. |
- Ben Rayana, Mohammed C., et al.
(författare)
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IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma
- 2008
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 46:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should yield comparable and unbiased results for iMg. This IFCC guideline on sampling, measuring and reporting iMg in plasma provides a prerequisite to achieve this goal [in this document, "plasma" refers to circulating plasma and the forms in which it is sampled, namely the plasma phase of anticoagulated whole blood (or "blood"), plasma separated from blood cells, or serum]. The guideline recommends measuring and reporting ionized magnesium as a substance concentration relative to the substance concentration of magnesium in primary aqueous calibrants with magnesium, sodium, and calcium chloride of physiological ionic strength. The recommended name is "the concentration of ionized magnesium in plasma". Based on this guideline, results will be approximately 3% higher than the true substance concentration and 4% lower than the true molality in plasma. Calcium ions interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus it is necessary to determine both ions simultaneously in each sample and correct the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent. Therefore, pH should be measured simultaneously with iMg to allow adjustment of the result to pH 7.4. The concentration of iMg in plasma may be physiologically and clinically more relevant than the concentration of total magnesium. Furthermore, blood-gas analyzers or instruments for point-of-care testing are able to measure plasma iMg using whole blood (with intact blood cells) as the sample, minimizing turnaround time compared to serum and plasma, which require removal of blood cells.
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| 4. |
- Ben Rayana, Mohammed C, et al.
(författare)
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Recommendation for measuring and reporting chloride by ISEs in undiluted serum, plasma or blood
- 2006
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 44:3, s. 346-352
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Tidskriftsartikel (refereegranskat)abstract
- The proposed recommendation for measuring and reporting chloride in undiluted plasma† or blood by ion-selective electrodes (ISEs) will provide results that are identical to chloride concentrations measured by coulometry for standardized normal plasma or blood samples. It is applicable to all current ISEs dedicated to chloride measurement in undiluted samples that meet the requirements. However, in samples with reduced water concentration, results by coulometry are lower than by ion-selective electrode due to volume displacement. The quantity measured by this standardized ISE procedure is called the ionized chloride concentration. It may be clinically more relevant than the chloride concentration as determined by coulometry, photometry or by ISE after dilution of the sample. © 2006 by Walter de Gruyter.
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| 5. |
- Börjel, Anna K., et al.
(författare)
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Novel mutations in the 5'-UTR of the FOLR1 gene
- 2006
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 44:2, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported two novel mutations in the 5'-untranslated region (UTR) of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations, 92 patient samples with elevated levels of homocysteine were screened by single-strand conformation polymorphism (SSCP) between nt -425 and -782, and -712 and -1110. Between nt -425 and -782 we did not find any mutations. Between nt -712 and -1110 there were three novel mutations. One subject had two mutations very close to each other, c.-856C>T and c.-921T>C. Two subjects had a c.-1043G>A mutation. To get an idea of the prevalence of FOLR1 mutations in an unselected population, we also screened 692 healthy school children for mutations. In this cohort, between nt -188 and +272 we discovered one novel mutation, a single nucleotide substitution, c.-18C>T, in addition to five children with the 25-bp deletion mutation previously described by us. Thus, so far we have discovered six novel mutations in the 5'-UTR region of the gene for folate receptor-alpha. We genotyped all 17 subjects with a FOLR1 mutation for the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism, and developed new single-nucleotide polymorphism (SNP) genotyping protocols for MTHFR 1298A>C and 1793G>A utilising Pyrosequencing technology. None of the 17 subjects had the 677TT genotype, which ruled out this as a cause of elevated homocysteine levels, which was observed in some of the subjects. Further studies of mutations in the 5'-UTR of FOLR1, and in particular of their interplay with folate intake status, are warranted.
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| 6. |
- D'Orazio, P., et al.
(författare)
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Approved IFCC recommendation on reporting results for blood glucose
- 2006
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 44:12, s. 1486-1490
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Tidskriftsartikel (refereegranskat)abstract
- In current clinical practice, plasma and blood glucose are used interchangeably with a consequent risk of clinical misinterpretation. In human blood, glucose is distributed, like water, between erythrocytes and plasma. The molality of glucose (amount of glucose per unit water mass) is the same throughout the sample, but the concentration is higher in plasma, because the concentration of water and therefore glucose is higher in plasma than in erythrocytes. Different devices for the measurement of glucose may detect and report fundamentally different quantities. Different water concentrations in the calibrator, plasma, and erythrocyte fluid can explain some of the differences. Results for glucose measurements depend on the sample type and on whether the method requires sample dilution or uses biosensors in undiluted samples. If the results are mixed up or used indiscriminately, the differences may exceed the maximum allowable error for glucose determinations for diagnosing and monitoring diabetes mellitus, thus complicating patient treatment. The goal of the International Federation of Clinical Chemistry and Laboratory Medicine, Scientific Division, Working Group on Selective Electrodes and Point of Care Testing (IFCC-SD-WG-SEPOCT) is to reach a global consensus on reporting results. The document recommends reporting the concentration of glucose in plasma (in the unit mmol/L), irrespective of sample type or measurement technique. A constant factor of 1.11 is used to convert concentration in whole blood to the equivalent concentration in plasma. The conversion will provide harmonized results, facilitating the classification and care of patients and leading to fewer therapeutic misjudgments. © 2006 by Walter de Gruyter.
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| 7. |
- Flodin, Mats, et al.
(författare)
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Variations in assay protocol for the Dako cystatin C method may change patient results by 50% without changing the results for controls
- 2006
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 44:12, s. 1481-1485
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cystatin C is increasingly used as a glomerular filtration marker, but so far only a few companies produce most of the cystatin C reagents suited for turbidimetry or nephelometry use in clinical laboratories. Methods: We studied different protocols for measuring cystatin C on an Architect ci8200 system using cystatin C reagents from Dako (Glostrup, Denmark). The results were compared with those obtained with Dade Behring reagents (Deerfield, IL, USA) on a BN ProSpec system. Results: Differences in assay protocol on the same instrument with the Dako reagent yielded an up to 50% difference in glomerular filtration rate calculated from the cystatin C results when analyzing patient samples, but had no effect on the results for controls. There were also significant differences regarding linearity and kinetics between samples and controls/calibrators. Conclusions: The results indicate different reactivity of the Dako antibodies against calibrators and controls in comparison with patient samples, highlighting the importance of using controls and calibrators that do not differ from patient samples.
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| 8. |
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| 9. |
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| 10. |
- Gellerstedt, Martin, 1966-, et al.
(författare)
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Partitioning reference values for several subpopulations using cluster analysis
- 2007
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Ingår i: Clinical chemistry and laboratory medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 45:8, s. 1026-1032
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A crucial question when developing reference intervals is whether different subpopulations need their own reference interval or if a single joint reference interval can be used. It is reasonable to use partitioned reference intervals in situations where a single interval results in considerable variation in sensitivity between subpopulations. The aim of partitioning is to harmonize the sensitivity of the reference intervals, i.e., to make the sensitivity similar for all patients, regardless of patient characteristics. Statistical criteria to identify when partitioning is adequate have been developed over the last two decades. These criteria are applicable when considering two subpopulations, but recently a procedure for considering several subpopulations has been developed. When several subpopulations are considered, there is a possibility that some subpopulations could form a group or cluster that could share a common reference interval. However, there is no formal systematic approach to indicate how to divide these subpopulations into clusters. The aim of this study was to suggest such a systematic approach for clustering. METHODS: A clustering technique was applied to data including several subpopulations. The technique is based on measuring the distance between separated reference limits and successively pooling subpopulations divided by short distances. A cluster is defined by a group of subpopulations that are close to each other and that differ from subpopulations in another cluster. A cluster recruits new subpopulations as long as the subpopulations can be pooled without violating a partitioning criterion. CONCLUSIONS: We have suggested a procedure for partitioning a number of Gaussian (or Gaussian-transformable) subpopulations into clusters. This is the only formalized procedure indicating how to analyze several subpopulations and identify a suitable number of groups and reference intervals. Using a computer program developed for partitioning issues, the approach was easy to adopt.
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