34 research outputs found
Prevalence of maternally inherited diabetes and deafness in diabetic populations in the Netherlands
Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations
Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-Trøndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n = 626; HUNT2 n = 112; median follow-up = 6.9 years) were matched to 738 controls. Vitamin D [25(OH)D2 and 25(OH)D3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42–1.20); 0.94 (0.72–1.22); 1.12 (0.82–1.53) and 1.26 (0.79–2.01) for clinically pre-defined categories of ≤25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend = 0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend = 0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant
Decreased cerebral blood perfusion in an NIDDM patient with an A-to-G mutation in the mitochondrial gene; a possible contribution to cognition deficits in diabetes mellitus
Clinical utility of an automated immunochemiluminometric thyroglobulin assay in differentiated thyroid carcinoma
Background: Thyroglobulin (Tg) measurements are important in the follow-up of patients with differentiated thyroid carcinoma (DTC). We evaluated the analytical and clinical performance of a new automated immunochemiluminometric assay for Tg (Tg-ICMA; Nichols Advantage Tg; Nichols Institute Diagnostics). Methods: We used the Tg-ICMA to measure Tg concentrations in serum samples from 110 Tg antibody-negative DTC patients undergoing thyroid-hormone suppression therapy. Disease state at the time of measurement was assessed on the basis of routine follow-up data. We compared the clinical performance of this assay with the routinely used IRMA (ELSA-hTG; CIS Bio International). Results: The detection limit and functional sensitivity of the Tg-ICMA, based on direct calibration to CRM457, were 0.05 and 0.6 mu g/L, respectively. No Tg-IRMA-positive cases were missed by the Tg-ICMA. Tg was measurable by Tg-ICMA (0.6-8.6 mu g/L) but undetectable by Tg-IRMA (<1.5 mu g/L) in 12 patients (11%). Clinical data showed evidence of disease in 4 of 12 patients (33%). Conclusions: The Tg-ICMA is a sensitive and reproducible assay for identifying patients in follow-up for DTC with evidence of disease, but uncertainty remains with regard to interpreting findings of measurable serum Tg in patients with no evidence of disease. Follow-up data are required to determine the predictive value of these isolated Tg results. New concepts, i.e., serial Tg measurements and risk stratification of patients, need to be tested to confirm the applicability of this assay for clinical practice. (c) 2006 American Association for Clinical Chemistry
Thyroglobulin (Tg) recovery testing with quantitative Tg antibody measurement for determining interference in serum Tg assays in differentiated thyroid carcinoma
Background: Thyroglobulin (Tg) measurements are complicated by interference from Tg autoantibodies (TgAbs) or heterophilic antibodies (HAMAs). We used a new automated immunochemiluminometric assay (ICMA) with Tg recovery (TgR) on the Nichols Advantage (R) platform to reassess the clinical utility of recovery testing in detecting interference in serum Tg measurement in patients with differentiated thyroid carcinoma. Methods: We used 2 TgAb methods to detect Tg measurement interference with TgR and quantitative TgAb measurement in sera from 127 patients. In a limited number of samples, we used an RIA as comparison method because it appeared to be minimally affected by Tg. Results: Prevalence of TgAbs was 13% (17 of 127) in either 1 or both TgAb assays. A compromised TgR (= 70%) corresponded with TgAb negativity in both assays for 95 of 101 samples (94%). In 6 TgAb-positive sera with TgR within the reference interval, there were no discrepancies between RIA and ICMA results. We obtained discordant, RIA and ICMA results for 6 of 9 TgAb-positive sera with decreased TgR. In 1 TgAb-negative sample, the Tg result was falsely increased because of interference by HAMAs, as shown by an overrecovery of 126%. Conclusions: The Nichols Advantage TgR assay is a valuable complementary method to overcome the technical problem of interference by TgAbs or HAMAs in TgAb assays. Further studies are needed to confirm the potential added value of this TgR assay. (c) 2006 American Association for Clinical Chemistry
Molecular characterization of WFS1 in patients with Wolfram syndrome
Item does not contain fulltextWolfram (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome is a rare autosomal-recessive neurodegenerative disorder that is characterized by juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing impairment. A gene responsible for Wolfram syndrome (WFS1) has been identified on the short arm of chromosome 4 and subsequently mutations in WFS1 have been described. We have screened 12 patients with Wolfram syndrome from nine Dutch families for mutations in the WFS1-coding region by single-strand conformation polymorphism analysis and direct sequencing. Furthermore, we analyzed the mitochondrial genome for gross abnormalities and the A3243G point mutation in the leucyl-tRNA gene, because Wolfram syndrome shows phenotypic similarities with mitochondrial disease. Seven mutations in WFS1 were identified in six of nine families: two missense mutations, one frameshift mutation, one splice donor site mutation, and three deletions. In addition, a splice variant near the 5'UTR of WFS1 was identified, present in patient as well as control RNA samples in various percentages, alternating the translation initiation consensus sequence. Whether this WFS1 splice variant displays impaired translation efficiency remains to be determined. No MtDNA lesions were identified in any of the Wolfram patients. Our results demonstrate the usefulness of molecular analysis of WFS1 in the refinement of clinical diagnostic criteria for Wolfram syndrome that helps to dissect the clinically overlapping syndromes sharing diabetes mellitus and optic atrophy
Molecular characterization of WFS1 in patients with Wolfram syndrome
Wolfram (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome is a rare autosomal-recessive neurodegenerative disorder that is characterized by juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing impairment. A gene responsible for Wolfram syndrome (WTS1) has been identified on the short arm of chromosome 4 and subsequently mutations in WFS1 have been described. We have screened 12 patients with Wolfram syndrome from nine Dutch families for mutations in the WFS1-coding region by single-strand conformation polymorphism analysis and direct sequencing. Furthermore, we analyzed the mitochondrial genome for gross abnormalities and the A3243G point mutation in the leucyl-tRNA gene, because Wolfram syndrome shows phenotypic similarities with mitochondrial disease. Seven mutations in WTS1 were identified in six of nine families: two missense mutations, one frameshift mutation, one splice donor site mutation, and three deletions. in addition, a splice variant near the 5'UTR of WFS1 was identified, present in patient as well as control RNA samples in various percentages, alternating the translation initiation consensus sequence. Whether this WTS1 splice variant displays impaired translation efficiency remains to be deter mined. No MtDNA lesions were identified in any of the Wolfram patients. Our results demonstrate the usefulness of molecular analysis of WFS1 in the refinement of clinical diagnostic criteria for Wolfram syndrome that helps to dissect the clinically overlapping syndromes sharing diabetes mellitus and optic atrophy