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Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an... more
Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype–related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis betwe...
Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute... more
Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute myocardial infarction (n = 28, AMI), valve surgery (n = 35, VALVE), coronary bypass surgery (n = 35, CABG), and peripheral vascular surgery (n = 14, VASC). Anti-actin and anti-myosin antibodies were determined on admission and serially during a period of 90 days. Anti-actin and anti-myosin immune response (IgG, IgM) was expressed comparing absorbance of the patients' serum with a reference serum. In the different patient groups significantly (P less than 0.01) higher anti-actin and anti-myosin antibody concentrations were found on admission compared with age-matched control groups. During follow-up, all patient groups except the vascular surgery group showed a significant immune response against actin and myosin, with an immune response ratio (peak/admission) for AMA IgG and IgM respectively of 2.12 and 2.40 in the VALVE group, 1.30 and 1.99 in the CABG group, 1.42 and 1.48 in the AMI group and 1.66 and 1.25 in the MYO group; and for AAA IgG and IgM respectively of 1.57 and 3.00 in the VALVE group, 1.54 and 1.64 in the CABG group, 1.25 and 1.07 in the AMI group, and 1.42 and 1.42 in the MYO group. A significant correlation between pre-cardiac injury and peak post-cardiac injury anti-myosin and anti-actin autoantibody levels could be demonstrated suggesting that pre-injury sensitization to these antigens plays an important role in evoking post-cardiac injury immune response.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) in multiple myeloma (MM) patients after treatment compared to the international myeloma working group... more
To evaluate the value of the combined evaluation of SE MRI, dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI) in multiple myeloma (MM) patients after treatment compared to the international myeloma working group (IMWG) response criteria. The retrospective study includes 27 newly diagnosed patients, providing 99 MRI-investigations. Patients were categorized according to the IMWG response criteria. Quantitative assessment was based on signal intensities (SI) of T1-weighted, fat-saturated T2-weighted and b1000 images, apparent diffusion coefficients (ADC) and parameters from time-intensity-curves (TIC) derived from L3. Qualitative visual analysis of conventional MRI-images, b1000-images and TICs, providing a "combined skeletal score", was used to create MRI response criteria. The combined skeletal score could significantly differentiate between subgroups based on IMWG response criteria (p=0.016). The gold standard plasmacytosis could significantly differentiate between subgroups based on MRI response criteria (p<0.001), as well as slope (p<0.001) and ADC (p=0.006). There is a good agreement between IMWG and MRI response criteria (Kendall's coefficient=0.761). Response evaluation of MM-patients based on the combination of anatomical information from conventional MRI with functional information from DCE-MRI and DWI, is useful for monitoring therapy.
Objectives Alpha-1 antitrypsin (A1AT) deficiency was first identified in patients with emphysema by the absence of the α1 band on serum protein electrophoresis (SPE). Today, capillary zone electrophoresis is widely performed in... more
Objectives Alpha-1 antitrypsin (A1AT) deficiency was first identified in patients with emphysema by the absence of the α1 band on serum protein electrophoresis (SPE). Today, capillary zone electrophoresis is widely performed in laboratories. Here, we compared two SPE systems to detect decreased A1AT concentrations to optimize their use as a screening tool for A1AT deficiency. Methods Serum protein electrophoresis was performed on 200 samples on the Capillarys 2 and the V8 Nexus. The latter presents two α1 bands (α1 band 1 and 2) while the Capillarys 2 has only one (Capillarys 2 total α1). The measures of A1AT and α1 acid glycoprotein (AAG) were performed as well as the phenotyping of M, S and Z alleles. Results At a A1AT cutoff of 0.80 g/L, a cutoff of 1.21 g/L using the V8 Nexus α1 band 2 corresponded to a 100% sensitivity and a 92.4% specificity while a 1.69% cutoff corresponded to a 100% sensitivity and a 92.4% specificity. The performance of the α1 band 1 was suboptimal and rather corresponded to AAG. On the Capillarys 2, a cutoff of 2.0 g/L corresponded to a 75.0% sensitivity and a 86.6% specificity, while a 3.2% cutoff showed a 96.4% sensitivity and a 67.4% specificity. The V8 Nexus α1 band 2 was the method the most correlated with A1AT (r=0.90–0.94). Conclusions The V8 Nexus α1 band 2 was the best predictor of A1AT deficiency, probably owing to a better resolution. The use of SPE was however unable to predict each phenotype. Phenotype or genotype studies are therefore still advisable in case of A1AT deficiency.
Abstract Recently a number of glucose dehydrogenase-based point of care (POCT) systems for glucose monitoring were successfully introduced on the market. Icodextrin, a glucose polymer is widely used as an osmotic agent in continuous... more
Abstract Recently a number of glucose dehydrogenase-based point of care (POCT) systems for glucose monitoring were successfully introduced on the market. Icodextrin, a glucose polymer is widely used as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD). Its metabolites are substrates for glucose dehydrogenase, inducing an analytical error which is gaining importance in the determination of glucose in a hospital environment. Since icodextrin is hydrolysed by amylase in the extracellular fluids, the analytical error in vivo is aggravated by the presence of the smaller oligosaccharides which originate from amylase activity. Clinicians should be warned about the spurious high glucose results which might occur in icodextrin-treated patients. In particular in conditions associated with increased amylase activities, analytical errors are to be expected in icodextrin-treated patients. Alternative glucose determination methods should be recommended in the latter group of patients.
The selective multi-protein analyser Behring Nephelometer was examined according to the ECCLS guidelines in a multicentre evaluation involving five laboratories. IgG, IgA, IgM, C-reactive protein, C3c, C4, apolipoprotein A-I and B were... more
The selective multi-protein analyser Behring Nephelometer was examined according to the ECCLS guidelines in a multicentre evaluation involving five laboratories. IgG, IgA, IgM, C-reactive protein, C3c, C4, apolipoprotein A-I and B were measured in serum, and albumin and IgG were measured in cerebrospinal fluid. All values obtained were included in the evaluation without correcting for outliers. The trial, which lasted three months and involved over 20,000 analyses, basically yielded the following results: 1. The precision was generally better than that of comparative procedures. For the majority of methods, the between-day coefficients of variation were below 4.5%. The highest coefficient of variation was 7.2% (for C-reactive protein) and the lowest 1.35% (for C3c). 2. The fraction of assigned values of control materials varied between 0.95 and 1.08. 3. Good agreement was found with results from the comparison procedures: Beckman ICS, Behring Laser Nephelometer, Hyland Laser Nephelometer. 4. No carry-over effects were observed. 5. No interferences were observed for IgG, IgA and IgM determinations using hyperbilirubinaemic or haemolytic samples. In contrast lipaemic samples and some with monoclonal immunoglobulin M showed an influence on the immunoephelometric reaction. 6. Because of the large measuring range, it is necessary to repeat analyses only in extremely rare cases. 7. During the entire evaluation period no instrument malfunctions or interruptions occurred. As a result of its reliability, the Behring Nephelometer is well suited for routine operation and emergency analyses in medium and large-sized laboratories.
Objective: Although indirect immunofluorescence (IIF) is the most widely applied screening test for antinuclear antibodies (ANA), it lacks specificity for the identification of specific diseases or antigen reactivities. The aim of the... more
Objective: Although indirect immunofluorescence (IIF) is the most widely applied screening test for antinuclear antibodies (ANA), it lacks specificity for the identification of specific diseases or antigen reactivities. The aim of the present study was to validate an anti-extractable nuclear antigen (ENA) screening strategy encompassing a three-step cascade whereby an ELISA with pooled specific ENA is positioned between the IIF and the final anti-ENA identification. Methods: Sera from 4 populations were tested for anti-ENA using an automated ELISA (EliA Symphony) and a line immunoassay (INNO-LIA ANA update). Results: At the manufacturer's cut-off, a 96% sensitivity (95% CI 94%-98%) and 96% specificity (95% CI 94%-98%) of EliA Symphony for anti-ENA was obtained in a consecutive selection of 328 IIF positive serum samples referred for ANA testing. In addition, a high sensitivity was demonstrated for anti-ENA reactivities in patients with SLE (99%, 95% CI 97%-101%) and SSc (100%), and for anti-ENA monoreactivities. Conclusion: The EliA Symphony test was shown to be a sensitive second-line screening test for anti-ENA antibodies. In the context of a high clinical suspicion of connective tissue disease or autoreactivities not included in the EliA Symphony assay, third-line testing may be useful, even if the anti-ENA screening is negative.
In the critically ill, the pre-analytical aspects of blood gas analysis still require attention from the clinician. Sampling and transport remain critical factors. Use of drugs may create analytical interferences for common analytes like... more
In the critically ill, the pre-analytical aspects of blood gas analysis still require attention from the clinician. Sampling and transport remain critical factors. Use of drugs may create analytical interferences for common analytes like glucose and protein. Icterus may falsely reduce creatinine and albumin values. Changes in the serum or plasma matrix (reduction of protein, increased covolume of solutes, ...) may furthermore cause important effects on the distribution of electrolytes. Enzyme activity measurements may be erroneous due to lack of essential oligoelements or reducing substances. Immunoassays may suffer from interferences caused by auto-antibodies. In case of hemolysis, a careful interpretation of test results is mandatory.

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