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Rotterdam, Netherlands

Zuiverloon T.C.M.,Erasmus Medical Center | Tjin S.S.,Erasmus Medical Center | Boeve E.R.,Sint Franciscus Gasthuis Rotterdam | Zwarthoff E.C.,Erasmus Medical Center
Journal of Urology | Year: 2011

Purpose: FGFR3 mutations occur in 70% of nonmuscle invasive bladder tumors. Although urine based FGFR3 mutation analysis can detect recurrence, its sensitivity may be limited if samples have few or no tumor cells. We determined whether test sensitivity depends on tumor size and the time point of urine collection, and how to increase sensitivity. Materials and Methods: A total of 440 urine samples from 18 patients with a suspicious bladder lesion at cystoscopy were collected during 6 days before surgery. Eight patients (300 samples) had an FGFR3 mutant tumor, including 4 each with a tumor greater than 3 and less than 1.5 cm. Polymerase chain reaction based FGFR3 analysis was done on all tumors and urine samples. Results: FGFR3 mutations were detected in 257 of the 300 urine samples (86%) from patients with an FGFR3 mutant tumor. Assay sensitivity was 100% for tumors greater than 3 cm and 75% for tumors less than 1.5 cm. It increased to 100% in patients with a less than 1.5 cm tumor when samples were pooled during 24 hours. Sensitivity was not influenced by the time of urine collection. All urine samples from patients with an FGFR3 wild-type tumor were negative for FGFR3 mutation. Conclusions: The sensitivity of tumor detection increased with tumor size. FGFR3 assay sensitivity depends on the number of shed tumor cells and improves by increasing urine volume. These findings suggest that there is an upper limit to the sensitivity of the FGFR3 assay when 1 urine sample is analyzed. This may also apply to other DNA or RNA based assays. © 2011 American Urological Association Education and Research, Inc.

Bovenberg S.A.,Sint Franciscus Gasthuis Rotterdam | Klop B.,Sint Franciscus Gasthuis Rotterdam | Alipour A.,Sint Franciscus Gasthuis Rotterdam | Martinez-Hervas S.,Hospital Clinico Universitario | And 9 more authors.
European Journal of Clinical Investigation | Year: 2012

Background Apolipoprotein (apo) B-containing lipoproteins are closely linked to atherogenesis. These lipoproteins are transported in plasma and are also associated with blood leucocytes. Our aim was to investigate whether apoB-containing lipoproteins are also present on the surface of erythrocytes and investigate the relationship with the presence of atherosclerosis in a cross-sectional study. Materials and methods Erythrocyte-bound apoB (ery-apoB) was measured by flowcytometry in subjects with (CAD+) and without coronary artery disease (CAD-), based on coronary angiography or on a history of cardiovascular disease. Intima media thickness (IMT) measurements were carried out using B-mode ultrasound. The relationship between ery-apoB and clinical and subclinical atherosclerosis was evaluated with binary logistic regression. Results A total of 166 subjects were included (40 CAD+ and 126 CAD-). ApoB was detected on freshly isolated erythrocytes (range: 0·1-5·5 au; mean±SEM 0·86±0·09 au) in all but nine subjects (four CAD+ and five CAD-). Ery-apoB was lower in CAD+ (0·62±0·09 au) compared to CAD- (1·18±0·10 au; P<0·001). Higher ery-apoB was associated with a lower risk of CAD (adjusted OR: 0·003 (95% CI: 0·001-0·08; P<0·001), but the protective effect was diminished with increasing age (adjusted OR: 1·10 (95% CI: 1·04-1·16; P<0·001). IMT was increased in CAD+ subjects (0·77±0·13mm) compared to CAD- (0·57±0·14mm; P<0·001). A significant negative association was found between ery-apoB and IMT (β=-0·214: 95% CI -0·284 to -0·145; P<0·001). There was no association between ery-apoB and plasma apoB (Pearson's r=-0·45; P=0·57). Conclusions Human erythrocytes carry apoB-containing lipoproteins. Subjects with atherosclerosis have lower ery-apoB. High ery-apoB may be protective against atherosclerosis and may reflect an alternative blood cell-mediated lipoprotein transport system in the circulation, in which these lipoproteins less likely interact with the endothelium. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

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