| 1. |
- Quétel, C. R., et al.
(författare)
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Methylmercury in tuna: demonstrating measurement capabilities and evaluating comparability of results worldwide from the CCQM P-39 comparison
- 2005
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Ingår i: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 20, s. 1058-66
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Tidskriftsartikel (refereegranskat)abstract
- Six metrology institutes (NMIs) representing at the Comité International des Poids et Mesures (CIPM) 4 Member States of the Metre Convention and 2 international organisations, and 8 expert laboratories selected outside CIPM have compared their capabilities to quantitatively measure methylmercury (MeHg) in a prepared tuna material containing approximately 4.3 mg kg–1 Hg. This comparison was the object of the CIPM–Comité Consultatif pour la Quantité de Matière (CCQM) Pilot Study 39, organised by the Institute for Reference Materials and Measurements (IRMM), from the European Commission—Joint Research Centre. Beside the test material itself, a bottle of the BCR-464 tuna Certified Reference Material (CRM) and an ampoule of IRMM-670, a 202Hg isotope enriched MeHg candidate isotopic CRM, were distributed to all participants, who were free to apply the measurement strategy of their choice. Four, including 1 NMI, relied on external calibration or the method of standard additions, whereas the other 10 implemented an isotope dilution mass spectrometry (IDMS) approach and chose to use the IRMM-670 for their measurements. Alkaline digestion at room temperature (with manual shaking) or high temperature (under sonication, oven or hot plate conditions) was employed by most participants, with hydrochloric acid leaching the second most popular choice. Alkylation (4 phenylations, 4 ethylations and 3 propylations) in the aqueous phase was preferred by a large majority over butylation by the Grignard reaction. All participants were requested to estimate the uncertainty associated with their results and 9 out of 14 stated relative combined uncertainties below 6%(k= 2). Despite this apparent consensus, the perception of which factor caused the largest contribution to this estimation differed among participants because of the differences in the analytical methodologies deployed but also because of wide differences of the concepts of uncertainty estimation. The mixture mode(MM) median, calculated also from the measurement uncertainties stated by the participants, was 1.967 ± 0.204 × 10–5 mol kg–1(95% confidence). Twelve of the results were re-grouped within a range of less than 0.3 × 10–5 mol kg–1(MM median = 1.967 ± 0.162 × 10–5 mol kg–1, 95% confidence): they nearly all (1 exception) overlapped with each other within k= 2 stated uncertainties. For the other 2 results the uncertainty seemed to have been particularly underestimated as they lay, respectively, at more than 20% above and less than –40% below the overall average. The relative standard deviation of the results of 9 laboratories out of the 10 that applied IDMS was about 2.6%. It can be assumed from the degree of equivalence shown by 12 out of 14 study participants that, at present, laboratories worldwide are potentially able to supply accurate results for MeHg in fish-type matrices (containing about 2 × 10–5 mol kg–1) within ±10% uncertainty. This encouraging outcome permitted scheduling of a follow-up CCQM-K43 key comparison for a lower MeHg content level in salmon tissues.
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| 2. |
- Kuypers, Dirk R., et al.
(författare)
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Mycophenolic Acid Exposure after Administration of Mycophenolate Mofetil in the Presence and Absence of Ciclosporin in Renal Transplant Recipients
- 2009
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Ingår i: Clinical Pharmacokinetics. - 0312-5963. ; 48:5, s. 329-341
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: The pharmacokinetics of mycophenolic acid (MPA) are complex, with large interindividual variability over time. There are also well documented interactions with ciclosporin, and assessment of MPA exposure is therefore necessary when reducing or stopping ciclosporin therapy. Here we report on the pharmacokinetic and pharmacodynamic behaviour of MPA in renal transplant patients on standard dose, reduced dose and no ciclosporin. Study design: The CAESAR study, a prospective 12-month study in primary renal allograft recipients, was designed to determine whether mycophenolate mofetil-based regimens containing either low-dose ciclosporin or low-dose ciclosporin withdrawn by 6 months could minimize nephrotoxicity and improve renal function without an increase in acute rejection compared with a mycophenolate mofetil-based regimen containing standard-dose ciclosporin. Patients and methods: A subset of patients from the CAESAR study contributed to this pharmacokinetic analysis of MPA exposure. Blood samples were taken over one dosing interval on day 7 and at months 3, 7 and 12 post-transplantation. The sampling timepoints were predose, 20, 40 and 75 minutes and 2, 3, 4, 6, 9 and 12 hours after mycophenolate mofetil dosing. Assessments included plasma concentrations of MPA and mycophenolic acid glucuronide (MPAG) and ciclosporin trough concentrations. The area under the plasma concentration-time curve (AUC) from 0 to 12 hours (AUC(12)) for MPA was the primary pharmacokinetic parameter, and the AUC12 for MPAG was the secondary parameter. Results: In total, 536 de novo renal allograft recipients were randomized in the CAESAR study. Of these, 114 patients were entered into the pharmacokinetic substudy and 110 patients contributed to the pharmacokinetic analysis. There was a rapid rise in MPA concentrations (median time to peak concentration 0.72-1.25 hours). At day 7 and month 3, the MPA AUC12 values were similar in the ciclosporin withdrawal and low-dose ciclosporin groups (patients with the same ciclosporin target concentrations to month 6), while at 7 and 12 months, the values in the ciclosporin withdrawal group were higher than in the low-dose group (19.9% and 30.2% higher, respectively). MPA AUC12 values in the standard-dose ciclosporin group were lower than in the other groups at all timepoints and increased over time. At all timepoints, the MPA peak plasma concentration was similar in all groups, and the MPAG concentrations rose more slowly than MPA concentrations. The ratio of the AUC from 6 to 12 hours/AUC(12) suggests that an increasing AUC in the ciclosporin withdrawal group is due to an increase in the enterohepatic recirculation. Conclusion: These findings are consistent with the hypothesis that ciclosporin inhibits the biliary secretion and/or hepatic extraction of MPAG, leading to a reduced rate of enterohepatic recirculation of MPA. Several concurrent mechanisms, such as ciclosporin-induced changes in renal tubular MPAG excretion and enhanced elimination of free MPA through competitive albumin binding with MPAG, can also contribute to the altered MPAG pharmacokinetics observed in the presence and absence of ciclosporin.
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| 3. |
- Snell, GI, et al.
(författare)
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Evaluation of techniques for lung transplantation following donation after cardiac death
- 2006
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 81:6, s. 2014-2019
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Tidskriftsartikel (refereegranskat)abstract
- Background. Lung transplantation using "donation after cardiac death" donors is a potential means to alleviate the shortage of suitable donor lungs for transplantation, but the practicality and utility of the various possible techniques need to be clarified. Methods. Using a dog model, we explored seven variations of standoff (ischemic) time (50 to 240 minutes), topical cooling (60 to 120 minutes), and flush cooling and cold storage (30 to 140 minutes) to mimic different human donor lung retrieval scenarios that can follow donation after cardiac death. The functional status of donation after cardiac death donor lungs was assessed initially with a 250 mL pulmonary arterial blood flush while ventilating with 100% oxygen and then on an ex-vivo perfusion rig for 120 minutes after retrieval. Results. All lungs achieved an excellent pO(2)/FiO(2) ratio ranging from 472 to 586 with stable pulmonary artery pressures and pulmonary vascular resistance and no net weight gain (952 +/- 221 g versus 1,006 +/- 235 g) during the 120-minute evaluation period. Initial blood flush correlated well with measured perfusion rig pO(2) at 30 minutes (R-2 = 0.63). Conclusions. This canine study suggests that lungs donated after cardiac death are reproducibly useable for transplantation with ischemic times of as long as 60 minutes. Although more study is needed, a blood flush evaluation is simple and may have a role as a secondary allograft assessment tool. The existing techniques of donor lung evaluation and preservation after donation following cardiac death thus appear both feasible and practical.
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| 4. |
- Szefer, P, et al.
(författare)
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Heavy-metal pollution of sediments from the Polish exclusive economic zone, southern Baltic Sea
- 2009
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Ingår i: Environmental Geology. - Berlin / Heidelberg : Springer. - 0943-0105 .- 1432-0495. ; 57:4, s. 847-862
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of 59 surface sediment samples from the Polish exclusive economic zone (EEZ) shows that Szczecin Lagoon sediments are the most polluted by heavy metals and that the degree of heavy-metal pollution decreases substantially on passing from the Szczecin Lagoon to the Pomeranian Bay and the inner shelf area and then on passing to the Bornholm Deep and Słupsk Furrow. Heavy-metal pollution in the sediments of the western part of the Polish EEZ therefore appears to follow the dispersion of the Oder River. Fluffy material from the Oder estuary appears to be the main source of heavy metals in the muddy sediments of the Bornholm Deep. The formation of sulphides is therefore not the principal factor controlling the enrichment of heavy metals in the sediments of this anoxic basin, although it may be responsible for the uptake of Mo, Sb and As. Two main factors control the distribution of the rare earth elements (REE) in sediments of the Polish EEZ: the input of Fe-organic colloids from rivers and the presence of detrital material in the sediments.
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| 5. |
- Wester, Elisabet Sjöberg, et al.
(författare)
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A simple screening assay for the most common JK*0 alleles revealed compound heterozygosity in Jk(a-b-) probands from Guam
- 2009
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Ingår i: Immunohematology. - 0894-203X. ; 25:4, s. 165-169
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Tidskriftsartikel (refereegranskat)abstract
- The Jk(a-b-) phenotype results from alterations in the JK gene and is characterized by absence of the RBC urea transporter in the cell membrane. The frequency of Jk(a-b-) varies among populations, but this phenotype is most commonly found in people of Polynesian and Finnish descent. Although rare, Jk(a-b-) individuals present a clinical challenge because anti-Jk3 is produced readily in response to transfusion and pregnancy, and Jk(a-b-) blood is not routinely available. Identification of Jk(a-b-) patients and donors is most often performed serologically. However, ten JK*o alleles have been identified, and this information can be used in DNA-based typing. We selected five JK*o alleles that had been encountered by our reference laboratory in two or more samples from unrelated individuals and designed an allele-specific primer PCR assay for use as an initial screening tool. After in-house validation, we tested genomic DNA from a family: a mother and her two sons referred to us for genetic investigation of their Jk(a-b-) phenotypes. Two different nucleotide substitutions, -1g>a in intron 5 (IVS5) and 956C>T in exon 10, originally associated with Polynesian and Indian/African populations respectively, were identified in the family. The mother and one son were compound heterozygotes, and the second son was homozygous for IVS5-1g>a. We conclude that the effort to design and validate such a screening assay was cost-efficient when compared with DNA sequencing costs. Furthermore, selection of the more common JK*o mutations was a practical approach that resulted in rapid identification of the genetic bases behind the Jk(a-b-) phenotypes in this unusual family. Although an obvious target for eventual inclusion into high-throughput genotyping platforms for clinical diagnostic services, current systems are very limited. Our approach provides a simple and inexpensive method for the identification of these rare alleles.
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