Overestimation of carboplatin doses is avoided by radionuclide GFR measurement.
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ABSTRACT:
SUBMITTER: Craig AJ
PROVIDER: S-EPMC3494427 | biostudies-other | 2012 Oct
REPOSITORIES: biostudies-other
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Project description:Background Direct quantitative measurement of GFR (mGFR) remains a specialized task primarily performed in research settings. Multiple formulas for estimating GFR have been developed that use the readily available endogenous biomarkers creatinine and/or cystatin C. However, eGFR formulas have limitations, and an accurate mGFR is necessary in some clinical situations and for certain patient populations. We conducted a prospective, open-label study to evaluate a novel rapid technique for determining plasma volume and mGFR.Methods We developed a new exogenous biomarker, visible fluorescent injectate (VFI), consisting of a large 150-kD rhodamine derivative and small 5-kD fluorescein carboxymethylated dextrans. After a single intravenous injection of VFI, plasma volume and mGFR can be determined on the basis of the plasma pharmacokinetics of the rhodamine derivative and fluorescein carboxymethylated dextrans, respectively. In this study involving 32 adults with normal kidney function (n=16), CKD stage 3 (n=8), or CKD stage 4 (n=8), we compared VFI-based mGFR values with values obtained by measuring iohexol plasma disappearance. VFI-based mGFR required three 0.5-ml blood draws over 3 hours; iohexol-based mGFR required five samples taken over 6 hours. Eight healthy participants received repeat VFI injections at 24 hours.Results VFI-based mGFR values showed close linear correlation with the iohexol-based mGFR values in all participants. Injections were well tolerated, including when given on consecutive days. No serious adverse events were reported. VFI-based mGFR was highly reproducible.Conclusions The VFI-based approach allows for the rapid determination of mGFR at the bedside while maintaining patient safety and measurement accuracy and reproducibility.
| S-EPMC6054356 | biostudies-literature
Project description:Background and objectivesOverestimation of GFR by urinary creatinine clearance (CrCl) at lower levels of GFR has long been attributed to enhanced creatinine secretion. However, this does not take into consideration the contribution of errors in measured GFR (and CrCl) due to short-term biologic variability or test imprecision.Design, setting, participants, & measurementsWe analyzed cross-sectional data among 1342 participants from the Chronic Renal Insufficiency Cohort study with baseline measurement of GFR by iothalamate clearance (iGFR) and CrCl by 24-hour urine collection. We examined the CrCl/iGFR ratio classified by categories of iGFR and also by categories of CrCl.ResultsOverall, mean CrCl/iGFR ratio was 1.13. CrCl/iGFR ratio was higher at lower iGFR categories. In contrast, this ratio was lower at lower CrCl levels. We hypothesize these relationships could be due to measurement error, which is bolstered by replicating these trends in a simulation and modeling exercise in which there was no variation in the ratio of CrCl/iGFR with true kidney function but taking into account the effect of measurement error in both CrCl and iGFR (of magnitudes previously described in the literature). In our simulated data, the observed CrCl/iGFR ratio was higher at lower observed iGFR levels when patients were classified by categories of observed iGFR. When the same patients were classified by categories of observed CrCl, the observed CrCl/iGFR ratio was lower at lower observed CrCl levels.ConclusionsThe combined empirical and modeling results suggest that measurement errors (in both CrCl and iGFR) should be considered as an alternative explanation for the longstanding observation that the ratio of CrCl to iGFR gets larger as iGFR decreases.
| S-EPMC5012489 | biostudies-literature
Project description:ContextVitamin D (VD) deficiency in pregnancy and the neonatal period has impacts on childhood outcomes. Maternal VD sufficiency is crucial for sufficiency in the neonate, though the effect of early versus late pregnancy 25-hydroxy-vitamin D (25(OH)D) levels on neonatal levels is unknown. Furthermore, chemiluminescence immunoassays (CLIAs) are widely used, though their validity in measuring 25(OH)D specifically in cord blood specimens has not been established.ObjectiveTo assess the validity of a CLIA in the measurement of cord blood 25(OH)D and to evaluate maternal determinants of neonatal 25(OH)D, including early versus late pregnancy 25(OH)D levels.DesignThis is an ancillary analysis from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized, double-blinded, placebo-controlled study.Participants and interventionA total of 881 pregnant women at high risk of having offspring asthma were randomized to receive VD supplementation or placebo. Serum samples were collected from mothers in early and late pregnancy and from offspring cord blood at birth. 25(OH)D levels were assayed by CLIA in all maternal and offspring samples and by LC-MS/MS in all offspring samples and a subset of 200 maternal third trimester samples.ResultsCord blood 25(OH)D levels were higher as measured by CLIA (mean 37.13 ng/mL [SD 18.30]) than by LC-MS/MS (mean 23.54 ng/mL [SD 11.99]), with a mean positive bias of 13.54 ng/mL (SD 12.92) by Bland-Altman analysis. This positive bias in measurement by CLIA was not observed in maternal samples. Third trimester 25(OH)D was a positive determinant of neonatal 25(OH)D levels.ConclusionChemiluminescence immunoassays overestimate 25(OH)D levels in human cord blood samples, an effect not observed in maternal blood samples. The quantification of 25(OH)D by CLIA should therefore not be considered valid when assayed in cord blood samples. Third trimester, but not first trimester, maternal 25(OH)D is one of several determinants of neonatal 25(OH)D status.
| S-EPMC7065842 | biostudies-literature
Project description:Intercellular CO2 concentration of leaves (Ci) is a critical parameter in photosynthesis. Nevertheless, uncertainties in calculating Ci arise as stomata close. Here, by modifying the assimilation chamber of a commercial gas-exchange equipment to directly measure Ci, we demonstrate overestimation of calculated Ci (i.e. Ci(c)) without stimulating stomatal closure. Gas exchange was measured on one side of the leaf while measured Ci (Ci(m)) was acquired simultaneously on the other side of the leaf in hypostomatous passion fruit (Passiflora edulis Sims) and amphistomatous sunflower (Helianthus annuus L.) and common bean (Phaseolus vulgaris L.). The adaxial surface showed comparable Ci(c) and Ci(m) in sunflower, whereas in common bean, where the adaxial surface has a low stomatal density, Ci(c) markedly differed from Ci(m) when the stomata remained open. However, the latter discrepancy disappeared when measuring the leaf flipped upside down so that the gas exchange was measured (i.e. Ci was calculated) on the abaxial side, which has a much higher stomatal density. The passion fruit showed the largest discrepancy on the astomatous side, indicating that the cuticle has a large impact on the calculation. Direct measurement of Ci is recommended as a more accurate estimate than the calculation when stomatal gas transport is restricted. Occurrence of overestimation and prospects for direct measurement are discussed.
| S-EPMC6018834 | biostudies-other
Project description:The d and f electrons in correlated metals are often neither fully localized around their host nuclei nor fully itinerant. This localized/itinerant duality underlies the correlated electronic states of the high-Tc cuprate superconductors and the heavy-fermion intermetallics and is nowhere more apparent than in the 5f valence electrons of plutonium. Here, we report the full set of symmetry-resolved elastic moduli of PuCoGa5--the highest Tc superconductor of the heavy fermions (Tc = 18.5 K)--and find that the bulk modulus softens anomalously over a wide range in temperature above Tc. The elastic symmetry channel in which this softening occurs is characteristic of a valence instability--therefore, we identify the elastic softening with fluctuations of the plutonium 5f mixed-valence state. These valence fluctuations disappear when the superconducting gap opens at Tc, suggesting that electrons near the Fermi surface play an essential role in the mixed-valence physics of this system and that PuCoGa5 avoids a valence transition by entering the superconducting state. The lack of magnetism in PuCoGa5 has made it difficult to reconcile with most other heavy-fermion superconductors, where superconductivity is generally believed to be mediated by magnetic fluctuations. Our observations suggest that valence fluctuations play a critical role in the unusually high Tc of PuCoGa5.
| S-EPMC4371925 | biostudies-literature
Project description:Prompt and repeated assessments of tumor sensitivity to available therapeutics could reduce patient morbidity and mortality by quickly identifying therapeutic resistance and optimizing treatment regimens. Analysis of changes in cancer cell biomass has shown promise in assessing drug sensitivity and fulfilling these requirements. However, a major limitation of previous studies in solid tumors, which comprise 90% of cancers, is the use of cancer cell lines rather than freshly isolated tumor material. As a result, existing biomass protocols are not obviously extensible to real patient tumors owing to potential artifacts that would be generated by the removal of cells from their microenvironment and the deleterious effects of excision and purification. In this present work, we show that simple excision of human triple-negative breast cancer (TNBC) tumors growing in immunodeficient mouse, patient-derived xenograft (PDX) models, followed by enzymatic disaggregation into single cell suspension, is enabling for rapid and accurate biomass accumulation-based predictions of in vivo sensitivity to the chemotherapeutic drug carboplatin. We successfully correlate in vitro biomass results with in vivo treatment results in three TNBC PDX models that have differential sensitivity to this drug. With a maximum turnaround time of 40 h from tumor excision to useable results and a fully-automated analysis pipeline, the assay described here has significant potential for translation to clinical practice.
| S-EPMC6312628 | biostudies-literature
Project description:Recent years have played witness to the advent of nuclear theranostics: the synergistic use of "matched pair" radiopharmaceuticals for diagnostic imaging and targeted radiotherapy. In this investigation, we report the extension of this concept to in vivo pretargeting based on the rapid and bioorthogonal inverse electron demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO). We demonstrate that a single injection of a TCO-modified immunoconjugate can be used as a platform for pretargeted PET imaging and radiotherapy via the sequential administration of a pair of Tz-bearing radioligands labeled with the positron-emitting radiometal copper-64 (t1/2 ? 12.7 h) and the beta-emitting radiometal lutetium-177 (t1/2 ? 6.7 days). More specifically, a mouse model of human colorectal carcinoma received a dose of the A33 antigen-targeting immunoconjugate huA33-TCO, followed 24 and 48 h later by injections of [64Cu]Cu-SarAr-Tz and [177Lu]Lu-DOTA-PEG7-Tz, respectively. This approach produces high activity concentrations of both radioligands in tumor tissue (16.4 ± 2.7 %ID/g for [64Cu]Cu-SarAr-Tz at 48 h post-injection and 18.1 ± 2.1 %ID/g for [177Lu]Lu-DOTA-PEG7-Tz at 120 h post-injection) as well as promising tumor-to-healthy organ activity concentration ratios. Ultimately, we believe that this work could not only have important implications in nuclear theranostics-most excitingly with isotopologue-based radioligand pairs such as [64Cu]Cu-SarAr-Tz and [67Cu]Cu-SarAr-Tz-but also in the delivery of fractionated doses during pretargeted radioimmunotherapy.
| S-EPMC7169955 | biostudies-literature
Project description:Estimating the proportion of adaptive substitutions (?) is of primary importance to uncover the determinants of adaptation in comparative genomic studies. Several methods have been proposed to estimate ? from patterns polymorphism and divergence in coding sequences. However, estimators of ? can be biased when the underlying assumptions are not met. Here we focus on a potential source of bias, i.e. variation through time in the long-term population size (N) of the considered species. We show via simulations that ancient demographic fluctuations can generate severe overestimations of ?, and this is irrespective of the recent population history.
| S-EPMC6012701 | biostudies-literature
Project description:Anxiety has been found to lengthen time perception, especially the time perception of negative stimuli. This anxiety-related time overestimation is thought to be mainly associated with massively increased arousal. Suppression, which can be achieved either deliberately or automatically, has been demonstrated to be effective in reducing arousal. Consequently, the present study explored the effectiveness of both deliberate suppression (Experiment 1) and automatic suppression (Experiment 2) in reducing the time distortion in anxiety. A temporal bisection task (TBT), featuring negative and neutral pictures, was used to measure time perception, while the self-reported arousal was used to assess arousal. The deliberate suppression was manipulated by asking participants to suppress their emotional expressions; while automatic suppression was manipulated through a sentence-unscrambling task featuring suppression-related words, which can unconsciously prime suppression. The results of Experiment 1 showed that deliberate suppression did not reduce the anxiety-related time overestimation and arousal. However, Experiment 2 showed that automatic suppression significantly reduced the anxiety-related time overestimation, with significant arousal reduction being observed. In conclusion, automatic suppression, but not deliberate suppression, is effective for reducing the effect of anxiety on time perception.
| S-EPMC7642764 | biostudies-literature
Project description:BackgroundRapid glomerular filtration rate (GFR) decline (>3 mL/min/1.73 m(2)) is an increasingly recognized high-risk diabetic nephropathy (DN) phenotype in Type 1 diabetes. Rapid GFR decline is a recognized predictor of impaired GFR (<60 mL/min/1.73 m(2)). However, the association between rapid GFR decline and renal hyperfiltration is not well described in Type 1 diabetes. We hypothesized that renal hyperfiltration (estimated glomerular filtration rate, eGFR ? 120 mL/min/1.73 m(2)) would predict rapid GFR decline over 6 years and that rapid GFR decline would predict impaired GFR at 6 years in adults with Type 1 diabetes.MethodsGFR was calculated by chronic kidney disease epidemiology (CKD-EPI) creatinine in 646 adults with Type 1 diabetes in the coronary artery calcification in Type 1 diabetes study. Logistic multivariable models were employed to investigate the relationships between renal hyperfiltration and rapid GFR decline, and rapid GFR decline and incident impaired GFR over 6 years.ResultsRenal hyperfiltration predicted greater odds of rapid GFR decline over 6 years [odds ratio (OR): 5.00, 95% confidence interval (CI): 3.03-8.25, P < 0.0001] adjusting for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), sex, duration, log of albumin/creatinine ratio and estimated insulin sensitivity. Furthermore, rapid GFR decline predicted greater odds of incident impaired eGFR (OR: 15.99, 95% CI 2.34-114.37, P = 0.006) in a similarly adjusted model. Sensitivity analyses with GFR calculated by CKD-EPI combined creatinine and cystatin C, and renal hyperfiltration defined as ?135 mL/min/1.73 m(2) yielded similar results.ConclusionsIn adults with Type 1 diabetes, rapid GFR decline over 6 years was associated with baseline renal hyperfiltration and incident GFR impairment. These observations may suggest an intermediate and predictive role of rapid GFR decline in the progression of DN.
| S-EPMC4838003 | biostudies-literature