Analytical evaluation and reference values of serum amyloid-A on the BN ProSpec.
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Biomedical subjects
Publications and source records attributed to Snjezana Rothkrantz-Kos.
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BACKGROUND AND AIM OF THE WORK: Studies on the relationship between fatigue and clinical parameters are sparse. In the present study this relationship was examined in a systematic way. METHODS: Patients with time since diagnosis < or = 2 years, visiting the outpatient clinic of the University Hospital Maastricht (n = 60; 34 untreated, 26 treated) were clinically evaluated and completed the Fatigue Assessment Scale (FAS). A representative sample of the Dutch population (n = 1893) also completed the FAS. Pulmonary disease severity was estimated from lung function test results and measures of metabolic derangement. Acute phase response markers high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and sarcoidosis activity parameters, soluble interleukin-2-receptor (sIL2R), and angiotensin-converting enzyme (ACE) were also measured. RESULTS: Only 27% of the sarcoidosis patients were diagnosed as non-fatigued (FAS score < 22), compared to 80% in the control population (n = 1893). In the sarcoidosis patients no sex differences and no differences in fatigue scores between the treated and the untreated groups were found. Patients with fatigue (FAS-score > or = 22) had lower DLCO values (p < 0.05). However, none of the tested clinical or serological parameters appeared to be a significant predictor of fatigue. CONCLUSIONS: In the present study, it was confirmed that fatigue is a major problem in sarcoidosis. The extent of fatigue could not be explained by clinical parameters. Thus, up to now, no clinical or physiological variable seems useful in predicting which patients are fatigued. In this light, the Fatigue Assessment Scale might be considered as a supplementary tool in sarcoidosis.
BACKGROUND: Previously, we demonstrated that the number of polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid (BALF) is useful in distinguishing sarcoidosis patients with a favorable outcome from those having a more severe course of disease. Neutrophils contain the oxidant-generating enzyme myeloperoxidase (MPO). Cellular levels of MPO can be influenced by functional promotor polymorphisms, ?463G/A and ?129G/A, which may modify disease severity. METHODS: In the present study, we investigated two MPO promotor polymorphisms in 110 sarcoidosis patients and in 191 ethnically matched controls. Pulmonary disease severity was evaluated by means of radiographic staging, HRCT scoring, lung function, and exercise capacity testing. RESULTS: No significant differences were found between sarcoidosis patients and healthy controls with regard to either polymorphism. Nor was any association observed between ?463 G/A and ?129 G/A polymorphism and the severity of sarcoidosis. CONCLUSIONS: The functional MPO promotor polymorphisms ?463G/A and ?129G/A did not explain disease severity in the sarcoidosis population studied. Future studies are needed to identify predictive features useful in guiding therapeutic strategies and to determine difficult-to-treat cases.
BACKGROUND: The implementation of a high-sensitivity C-reactive protein (hs-CRP) assay as a routine laboratory parameter may be necessary. It would be most practical to use one CRP method giving reliable results for the whole concentration range. We report here the evaluation of two new hs-CRP methods, which cover both the low and the high concentration ranges. METHODS: The BN ProSpec hs-CRP (Dade Behring) and Synchron LX 20 PRO hs-CRP methods were compared with the existing hs-CRP IMMAGE method (taken as a reference) and, for the high concentration range, also with the routine Synchron LX 20 CRP method (all from Beckman). Agreement among methods was examined for 521 samples. Reference values were estimated in 291 blood donors. Additionally, the influence of sample turbidity, a major problem of the present Synchron LX20 CRP method, was evaluated. RESULTS: Measurement of CPR by the BN ProSpec was linear down to 0.2 mg/L, whereas the linearity of Synchron LX20 PRO showed some systematic discrepancies. Over the whole measured range (0.2-250 mg/L), precision (coefficient of variation, CV) was < or =3.7% for the BN ProSpec and < or =6.1% for the LX20 PRO. The Synchron LX20 PRO hs-CRP method was found to be superior to the current routine Synchron LX20 CRP method with regard to precision in the low concentration range and the influence of sample turbidity. Both in the low concentration range and especially in the high concentration range, large discrepancies between methods were observed. CONCLUSION: Although acceptable performance was found for the Synchron LX20 PRO hs-CRP method, overall the performance of the BN ProSpec hs-CRP method was superior. However, standardization among assays needs further improvement in both the low and the high concentration ranges.
BACKGROUND: Sarcoidosis is a multiorgan inflammatory granulomatous disorder of unknown origin for which adequate markers to monitor disease severity are lacking. The aim of this study was to evaluate the potential clinical usefulness of serologic markers of inflammation [high-sensitivity C-reactive protein (hs-CRP) and serum amyloid A (SAA)], T-cell activation [soluble interleukin-2 receptor (sIL2R)], and granuloma formation [angiotensin-converting enzyme (ACE)] for monitoring of sarcoidosis. METHODS: Of the 185 sarcoidosis patients who visited the Sarcoidosis Management Center between 1999 and 2002, we selected 144 nonsmoking patients: 73 untreated (group I) and 71 treated (group II). Subgroups of the untreated patients [group Ia (nonchronic group with time since diagnosis < or = 2 years) and group Ib (chronic group with time since diagnosis >2 years)] were evaluated separately. ROC curves and logistic regression analyses were used to compare the diagnostic accuracy of different markers to assess disease severity. Pulmonary disease severity was defined by lung function test results. RESULTS: In untreated subgroup Ia and the total untreated group (group I), sIL2R had the largest areas under the curves (AUCs; 0.891 and 0.799, respectively) and the highest sensitivity (82% and 64%), specificity (94% and 88%), and positive (82% and 70%) and negative (94% and 88%) predictive values among the evaluated markers in both untreated groups. Nevertheless, the confidence intervals for sIL2R AUC, sensitivity, and specificity were broad and partly overlapped those of ACE, hs-CRP, and SAA. In the treated group (group II), all four markers appeared to have comparable AUCs, ranging from 0.645 for SAA to 0.711 for sIL2R. CONCLUSION: sIL2R appears to be useful for monitoring respiratory disease severity in sarcoidosis. We recommend sIL2R measurement in the follow-up of patients with sarcoidosis.
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BACKGROUND AND AIM OF THE WORK: The glutathione system has a key role in the defence against oxidative stress. To function properly, this system needs NADPH to maintain glutathione (GSH) in its reduced form. We hypothesized that the clinical problems associated with sarcoidosis might be related to a decreased anti-oxidant defence and we therefore measured the activity of the NADPH-generating enzyme glucose-6-phosphate dehydrogenase (G6PD), the GSH-regenerating enzyme glutathione reductase (GR) and indirectly the level of NADPH in red blood cells from patients with sarcoidosis. METHODS: In a population of sarcoidosis (n = 88) patients, G6PD, GR and GR activity after incubation with chromate (GR-Cr) were measured in erythrocytes. A decreased concentration of NADPH was revealed by an increased GR-Cr (> 0.6 IU/g Hb). To exclude a mutation in the G6PD gene, sequencing was performed in cases with an abnormal GR-Cr. Sarcoidosis pulmonary disease severity was evaluated by means of laboratory data, radiographic staging, HRCT scoring, pulmonary function and exercise capacity testing. RESULTS: Fourteen (29.2%) females and one (2.5%) male demonstrated an increased GR-Cr test, indicative of a decreased NADPH level. Patients with an abnormal test result demonstrated also significantly increased ACE and GR values (p < 0.05). Only one female case (of 6 tested) appeared to have a mutation in the G6PD gene. CONCLUSION: In a considerable percentage of female patients with sarcoidosis, a decreased level of NADPH in the erythrocytes was found.