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  • Author: Michel R. Langlois x
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Abstract

Lipoprotein-related risk of cardiovascular disease (CVD) can be adequately predicted in subjects with elevated total cholesterol and low-density lipoprotein (LDL-)cholesterol using the available guidelines. However, individuals with dyslipidemia can have normal total- and LDL-cholesterol concentrations. Many statin-treated patients remain at high residual risk of CVD despite achieving LDL goals. The small dense LDL phenotype, frequently presenting with hypertriglyceridemia and low high-density lipoprotein (HDL-)cholesterol (lipid triad), may contribute to failure to identify and treat high-risk individuals. Therefore, calculated non-HDL-cholesterol is recommended as secondary therapeutic target to LDL-cholesterol in patients with hypertriglyceridemia and mixed dyslipidemia. On-treatment apolipoprotein B adds prognostic information to LDL- and non-HDL-cholesterol by indicating the total number of atherogenic lipoproteins, regardless of their cholesterol content. Risk may be higher than indicated in the risk estimation systems in additional subjects with elevated lipoprotein(a) and homocysteine concentrations. To improve the (post-)post-analytical phase of lipid tests, aiming for maximal health outcome effectiveness of test interpretation and utilization, laboratory professionals should deliver clinical added value services by providing readily interpreted and guideline-adjusted test reports, interpretative commenting, proactive reflex testing or recommending additional tests, and joining multidisciplinary cooperations in guideline development and cost/benefit studies.

Abstract

To face the economic pressures arising from the current socio-economic conjuncture, hospital laboratories are endangered by an increasing trend towards the outsourcing of clinical laboratory tests to external (mega-) laboratories. This should allow hospitals to meet their economic requirements, but with an increased risk of loss of medical quality and, mid- to long-term, loss of cost effectiveness of healthcare at the national level. To anticipate current developments (economical and technological) that inevitably will affect the future of laboratory medicine, hospital laboratories should be proactive and enhance efficiency, reduce costs by consolidation, integrate into regional networks, and form alliances or partnerships. To create additional value, the core competency of laboratory professionals must be refocused to provide medical knowledge services (consultative support to clinicians) related to in vitro diagnostic testing. To integrate cost-efficiency with medical quality, implementation of a matricial organization – operational vs. biomedical level – could be an interesting approach. This integrated structure should create total quality of laboratory testing, managing the entire medical diagnostic cycle from the pre-preanalytical to post-postanalytical phase.

Clin Chem Lab Med 2009;47:1195–201.

Abstract

In humans the iron status is influenced by environmental and genetic factors. Among them, the genetic polymorphism of the hemoglobin (Hb)-binding plasma protein haptoglobin (Hp) has been shown to affect iron turnover. The best known biological function of Hp is capture of free Hb in plasma to allow hepatic recycling of heme iron and to prevent kidney damage during hemolysis. In healthy males, but not in females, the Hp 2-2 phenotype is associated with higher serum iron, higher transferrin saturation, and higher ferritin than Hp 1-1 and 2-1. Moreover, serum ferritin correlates with monocyte L-ferritin content, which is also highest in Hp 2-2 subjects due to endocytosis of multimeric Hb-Hp 2-2 complexes by the recently identified Hb scavenger receptor CD163 in macrophages. This iron delocalization pathway, occurring selectively in Hp 2-2 subjects, has important biological and clinical consequences. The Hp polymorphism is related to the prevalence and the outcome of various pathological conditions with altered iron metabolism such as hemochromatosis, infections, and atherosclerotic vascular disease.

Abstract

Background: Haptoglobin (Hp) polymorphism has been associated with blood pressure regulation and essential hypertension. We investigated Hp polymorphism in patients with preeclampsia.

Methods: A total of 60 Caucasian women with preeclampsia were prospectively followed from hospital admission until delivery. Serum Hp phenotypes 1-1, 2-1, and 2-2 were determined by starch gel electrophoresis and compared with those in 200 normotensive controls of the same geographic and ethnic origin. Blood pressure and laboratory markers (serum uric acid, alanine aminotransferase, aspartate aminotransferase, platelet count, and 24-h proteinuria) were compared according to Hp phenotypes of preeclamptic women.

Results: We found a higher Hp1 allele frequency in the preeclamptic group than in normotensive controls (0.517 vs. 0.400, p<0.05). The Hp 1-1 phenotype was present in 28% of preeclamptic patients vs. 16% of the controls, with an odds ratio (95% CI) of 2.08 (1.05–4.08) for Hp 1-1 vs. the other Hp phenotypes. Diastolic (p<0.005) and systolic (p<0.05) blood pressure and proteinuria (p<0.05) were highest in Hp 1-1 patients. Other laboratory markers were not significantly different between Hp phenotype subgroups.

Conclusions: The Hp1 allele frequency was higher among preeclamptic patients and the Hp 1-1 phenotype was associated with more severe hypertension and proteinuria.

Clin Chem Lab Med 2006;44:924–8.

Abstract

A capillary zone electrophoresis method was developed for haptoglobin (Hp) phenotyping in hemoglobin (Hb) supplemented serum. The method allows a complete resolution of the major haptoglobin phenotypes Hp 1-1, Hp 2-1, and Hp 2-2 based on the difference in charge-to-mass ratio of their Hb-Hp complexes. Identification of these phenotypes was achieved by their significant differences in migration times and their marked difference in electrophoretic pattern. Our method showed full agreement with starch gel electrophoresis. Furthermore, following neuraminidase treatment of the serum, the Hp subtypes Hp1-1FF, FS and SS could be resolved, based on the same criteria as the phenotyping. The new electrophoretic method allowed typing of the rare phenotypes Hp 2-1 modified (Hp 2-1M) and Hp Johnson. The calculated hemoglobin binding capacity of serum correlates well with the nephelometrically determined haptoglobin concentration. The new method for typing haptoglobin gives prospectives for fast haptoglobin typing and Hp 1-1 subtyping.

Abstract

Background: Calprotectin is a 36 kDa calcium and zinc binding protein. An increased level of calprotectin points towards inflammatory bowel disease. However, the biomarker calprotectin shows 14 potential cleavages sites for trypsin. Next to trypsin, also the presence of its inhibitor α1-antitrypsin after a gastrointestinal bleeding may affect calprotectin testing. In this study, effects of trypsin and α1-antitrypsin as potential confounders for faecal calprotectin testing are investigated.

Methods: An in vitro model was created. As calprotectin source, leukocytes were isolated and subsequently lysed (1% Triton X-100) and diluted in faecal matrix. Trypsin digestion was carried out by adding trypsin. Incubation occurred for 24 h or 48 h (37 °C). To study the influence of α1-antitrypsin on trypsin, the same experiment was repeated after adding serum containing α1-antitrypsin.

Results: In vitro experiments enabled monitoring of the faecal calprotectin digestion, leading to loss of immunoreactivity. Trypsin activity was a potential confounder in the interpretation of calprotectin, in particular for proximal lesions, where exposure of calprotectin to trypsin is prolonged. Relative calprotectin loss was proportional to the amount of trypsin. Decrease of calprotectin was more pronounced after 48 h of incubation in comparison to 24 h of incubation. Analogue experiments also showed stable calprotectin values after adding α1-antitrypsin.

Conclusions: Transit time, trypsin activity and addition of blood as a source of α1-antitrypsin may be regarded as potential confounders in the interpretation of calprotectin results. Age-related cut-off values depending on the anatomical localisation of the lesions could improve the diagnostic efficiency of calprotectin testing.

Abstract

Background: Three adult patients presented with unexpectedly high thyrotropin (TSH) concentrations that were discordant with clinical and biochemical findings of euthyroid or hyperthyroid status.

Methods: Antibody interference in the TSH immunoassay (Roche) was investigated by polyethylene glycol (PEG)-pretreatment, heterophilic blocking tube (HBT)-pretreatment, rheumatoid factor (RF) testing, immunofixation, protein A adsorption, and gel filtration chromatography (GFC).

Results: PEG-precipitation yielded <20% recovery of serum TSH, whereas HBT-pretreatment did not decrease TSH test results. RF-testing and immunofixation were negative. Protein A adsorption and GFC demonstrated the presence of TSH-immunoglobulin complexes in serum.

Conclusions: Interference by TSH-immunoglobulin complexes should be ruled out in euthyroid and hyperthyroid patients presenting with inappropriately increased or non-suppressed TSH values.

Clin Chem Lab Med 2009;47:604–6.

Abstract

Low-density lipoproteins (LDLs) are susceptible to structural modifications by oxidation, particularly the small dense LDL particles. The formation of lipid peroxidation derivates, such as thiobarbituric reactive substances, conjugated dienes, lipid hydroperoxides, and aldehydes, is associated with changes in apolipoprotein conformation and affects the functional properties of LDLs. Oxidized LDL (oxLDL) formation in the subendothelial space of the arterial wall is a key initiating step in atherosclerosis because it contributes to foam cell generation, endothelial dysfunction, and inflammatory processes. In the last decade, immunoassays were developed using monoclonal antibodies against oxidation-dependent epitopes of LDL which made it possible to directly measure oxLDL in the circulation. Increased circulating oxLDL concentrations have been related to cardiovascular disease in some studies, although not always independently after adjustment of classical lipid markers. The Asklepios Study, investigating 2524 healthy middle-aged subjects, showed that circulating oxLDL is affected by many biological and lifestyle factors, as well as (generalized) subclinical atherosclerosis.

Clin Chem Lab Med 2009;47:128–37.