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1.
Clin Chim Acta ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001233

RESUMO

BACKGROUND: Determining diagnostic thresholds for cardiac troponin assays is key to interpreting their clinical performance. We describe the calculation of 99th percentile upper reference limits (URLs) for the Elecsys® Troponin T Gen 5 (TnT Gen 5) assay. METHODS: Plasma and serum samples from healthy US participants were prospectively evaluated using TnT Gen 5 Short Turn Around Time and 18-min assays on cobas e 411 and cobas e 601 analyzers (Roche Diagnostics); thus, up to 8 TnT Gen 5 results per participant. RESULTS: A total of 10,402 TnT Gen 5 results from 1,301 participants were included (50.4% female). Across 9 calculation methods, overall 99th percentile URL was 19.2 ng/l (females, 13.5-13.6 ng/l; males, 21.4-22.2 ng/l). Across different sample/assay/analyzer combinations, overall 99th percentile URLs ranged 18.4-20.2 ng/l. Median TnT Gen 5 results increased with age, were higher in males, and ranged 3.0-3.7 ng/l across races/ethnicities and 3.0-3.6 ng/l across body mass index (BMI) classes. Applying additional exclusion criteria (N-terminal pro-brain natriuretic peptide, BMI and estimated glomerular filtration rate) resulted in lower 99th percentile URLs (overall, 16.9 ng/l; females, 11.8 ng/l; males, 18.5 ng/l). CONCLUSION: Our findings facilitate the interpretation of TnT Gen 5 results in US clinical practice.

2.
J Anal Toxicol ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696920

RESUMO

Vitreous humor is a potential alternative matrix for postmortem toxicology drug screens when peripheral blood is unavailable. It is easily and reliably collected and may not suffer from the same postmortem redistribution as seen in blood. Here, we compared the concentrations of 7 acidic drugs (acetaminophen, ibuprofen, naproxen, salicylic acid, carbamazepine, phenobarbital and phenytoin) in peripheral blood and vitreous fluid collected in 89 autopsy cases. Analysis was done by high-performance liquid chromatography with diode-array detection. Overall, we found that vitreous drug concentrations were significantly lower than peripheral blood with median vitreous to peripheral blood (V/PB) ratios ranging from 0.0 to 0.6 (mean, 0.1-0.6). The correlations between the concentrations of over-the-counter analgesics in peripheral blood versus vitreous fluid were poor, with acetaminophen exhibiting the best linearity (R2 = 0.72). The antiepileptic drugs (carbamazepine, phenytoin and phenobarbital) exhibited good correlations between peripheral blood and vitreous humor, with all exhibiting an R2 ≥ 0.95. Overall, we have demonstrated the potential of vitreous fluid as an alternative matrix for the detection of select acidic drugs.

3.
J Appl Lab Med ; 4(3): 415-421, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31659079

RESUMO

BACKGROUND: Oral biotin supplementation is known to interfere with biotin-streptavidin-based immunoassays, including Roche's fifth-generation cardiac troponin T (cTnT) assay, which plays a critical role in the diagnosis of myocardial infarction (MI). The utility of dilution, a quick and easy method to detect and remove interferences, has not been published for biotin interference. METHODS: Concentrations of cTnT were measured in pooled serum from clinical samples. Serum samples were supplemented with biotin to known concentrations, then cTnT concentrations were remeasured to assess for biotin interference. Samples were then diluted to assess for effective removal of biotin interference. RESULTS: At cTnT values near the critical reporting range for our institution (100 ng/L) we observed significant interference in measured values with added biotin concentrations above 50 ng/mL. In specimens without added biotin, autodilution at a 1:10 ratio yielded a mean 157% capture of measured cTnT, precluding the use of autodilution for detecting and mitigating biotin interference. A 1:10 dilution with serum containing 20-30 ng/L cTnT yielded a mean capture of 107%, which was suitable for detecting underlying biotin interference in supplemented samples. CONCLUSIONS: Biotin interference, at supraphysiologic concentrations, may create an artifactual reduction in measured cTnT to levels that could lead to delayed detection of an MI. Dilution with serum of known cTnT concentration of 20-30 ng/L is a fast and effective method to mitigate the analytical consequences of biotin interference.

4.
Clin Chem Lab Med ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31527291

RESUMO

Background The widespread availability of cannabis raises concerns regarding its effect on driving performance and operation of complex equipment. Currently, there are no established safe driving limits regarding ∆9-tetrahydrocannabinol (THC) concentrations in blood or breath. Daily cannabis users build up a large body burden of THC with residual excretion for days or weeks after the start of abstinence. Therefore, it is critical to have a sensitive and specific analytical assay that quantifies THC, the main psychoactive component of cannabis, and multiple metabolites to improve interpretation of cannabinoids in blood; some analytes may indicate recent use. Methods A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to quantify THC, cannabinol (CBN), cannabidiol (CBD), 11-hydroxy-THC (11-OH-THC), (±)-11-nor-9-carboxy-Δ9-THC (THCCOOH), (+)-11-nor-Δ9-THC-9-carboxylic acid glucuronide (THCCOOH-gluc), cannabigerol (CBG), and tetrahydrocannabivarin (THCV) in whole blood (WB). WB samples were prepared by solid-phase extraction (SPE) and quantified by LC-MS/MS. A rapid and simple method involving methanol elution of THC in breath collected in SensAbues® devices was optimized. Results Lower limits of quantification ranged from 0.5 to 2 µg/L in WB. An LLOQ of 80 pg/pad was achieved for THC concentrations in breath. Calibration curves were linear (R2>0.995) with calibrator concentrations within ±15% of their target and quality control (QC) bias and imprecision ≤15%. No major matrix effects or drug interferences were observed. Conclusions The methods were robust and adequately quantified cannabinoids in biological blood and breath samples. These methods will be used to identify cannabinoid concentrations in an upcoming study of the effects of cannabis on driving.

5.
Clin Chim Acta ; 495: 522-528, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152695

RESUMO

BACKGROUND: We report the analytical performance of the Elecsys® Troponin T Gen 5 STAT (TnT Gen 5 STAT; Roche Diagnostics) assay. METHODS: Measuring limits/ranges were determined in lithium-heparin plasma samples per Clinical and Laboratory Standards Institute (CLSI) EP17-A2. Precision was evaluated per CLSI EP05-A2 using lithium-heparin plasma/quality control samples on cobas e 411/cobas e 601 analyzers; two duplicated runs per day for 21 days (n = 84). Cross-reactivity with other troponin forms and interference from endogenous substances/drugs was tested; recovery criterion for no cross-reactivity was within ±10%. RESULTS: Coefficients of variation (CV) for repeatability/intermediate precision were 0.7-5.6%/1.4-10.3% (cobas e 411; mean cardiac troponin T [cTnT]: 7.3-9341 ng/L) and 0.7-3.0%/1.5-6.4% (cobas e 601; mean cTnT: 7.4-9455 ng/L). There was no cross-reactivity with skeletal muscle troponin T (≤ 10,000 ng/L), skeletal muscle troponin I (≤ 100,000 ng/L), cardiac troponin I (≤ 10,000 ng/L), or human troponin C (≤ 80,000 ng/L). No interference was observed with biotin (≤ 20 ng/mL) or 34 drugs. CONCLUSION: The TnT Gen 5 STAT assay demonstrated a CV of <10% at the 99th percentile upper reference limit, meeting precision requirements (Fourth Universal Definition of Myocardial Infarction) for high-sensitivity troponin assays.


Assuntos
Análise Química do Sangue/métodos , Imunoensaio/métodos , Troponina T/sangue , Humanos , Limite de Detecção , Medições Luminescentes , Reprodutibilidade dos Testes
6.
Clin Chim Acta ; 491: 30-38, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30615854

RESUMO

A liquid chromatography tandem mass spectrometry method was developed for quantifying ten cannabinoids in oral fluid (OF). This method utilizes OF collected by the Quantisal™ device and concurrently quantifies cannabinol (CBN), cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-THC (11-OH-THC), 11-nor-9-carboxy-Δ9-THC (THC-COOH), 11-nor-9-carboxy-Δ9-THC glucuronide (THC-COOH-gluc), Δ9-THC glucuronide (THC-gluc), cannabigerol (CBG), tetrahydrocannabiverin (THCV), and Δ9-tetrahydrocannabinolic acid A (THCA-A). Solid phase extraction was optimized using Oasis Prime HLB 30 mg 96-well plates. Cannabinoids were separated by liquid chromatography over a BEH C18 column and detected by a Waters TQ-S micro tandem mass spectrometer. The lower limits of quantification (LLOQ) were 0.4 ng/mL for CBN, CBD, THC, 11-OH-THC, THC-gluc, and THCV; and 1.0 ng/mL for THC-COOH, THC-COOH-gluc, CBG and THCA-A. Linear ranges extended to 2000 ng/mL for THC and 200 ng/mL for all other analytes. Inter-day analytical bias and imprecision at three levels of quality control (QC) was within ±15%. Mean extraction efficiencies ranged from 26.0-98.8%. Applicability of this method was tested using samples collected from individuals randomly assigned to smoke either a joint containing <0.1%, 5.9%, or 13.4% THC content. This method was able to identify and calculate the concentration of 6 of 10 cannabinoids validated in this method.


Assuntos
Líquidos Corporais/química , Canabinoides/análise , Cromatografia Líquida/métodos , Testes de Química Clínica/métodos , Espectrometria de Massas em Tandem/métodos , Calibragem , Canabinoides/isolamento & purificação , Humanos , Modelos Lineares
7.
Clin Biochem ; 61: 18-22, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30236830

RESUMO

OBJECTIVE: A multisite investigation compared the analytical performance of a point-of-care (POC) HbA1c device with multiple commonly used HbA1c laboratory methods and an NGSP (National Glycohemoglobin Standardization Program) reference method. RESEARCH DESIGN AND METHODS: The Afinion AS100 POC device analyzed HbA1c using 618 EDTA whole blood excess patient specimens with clinically indicated HbA1c testing. Results were compared to measurements across five clinical laboratories and the NGSP reference method. Precision was evaluated over 8-10 consecutive days for low-, mid-, and high-range HbA1c specimens at all five sites. RESULTS: Over a wide range of HbA1c values (4.0%-15% HbA1c), 97.1% of the POC results and 94.5% of routine laboratory results fell within the target value of ±6% of the NGSP reference method results. The POC HbA1c results at 6.5% exhibited a total relative bias of -0.6% (-0.04% HbA1c) compared to the reference method while the aggregate of laboratory methods displayed a relative bias of -0.9% (-0.06% HbA1c). The total imprecision of the POC results ranged from 0.74-2.13% CV across the analytic measurement range compared to 0.81-3.23% CV for the routine laboratory methods. CONCLUSIONS: The accuracy and precision of the Afinion POC HbA1c method was comparable to the laboratory HbA1c methods supporting the FDA's recent approval of the Afinion HbA1c Dx device for use in the diagnosis of diabetes.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/análise , Testes Imediatos , Aprovação de Equipamentos , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Teste de Materiais , Reprodutibilidade dos Testes , Estados Unidos , United States Food and Drug Administration
8.
Clin Lab Med ; 38(3): 527-537, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30115396

RESUMO

This article describes the need for, stratifies the complexity of, and proposes detailed lists of training competencies for diagnostic laboratory personnel using quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) for patient care. Although quantitative LC-MS/MS is evolving toward greater automation with less need for technical expertise, gaps remain in resources for training and assessment.


Assuntos
Cromatografia Líquida , Pessoal de Laboratório Médico/educação , Ciência de Laboratório Médico/educação , Ciência de Laboratório Médico/organização & administração , Espectrometria de Massas em Tandem , Competência Clínica , Humanos , Pessoal de Laboratório Médico/normas
9.
Clin Chim Acta ; 473: 35-38, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28801091

RESUMO

BACKGROUND: In this report, we describe 2 contrasting cases of hypervitaminosis D. CASE PRESENTATION: Patient 1 was a 75-y old man who developed symptomatic hypercalcemia (peak serum calcium concentration of 15.3mg/dl; reference range: 8.5-10.6mg/dl), cardiac injury, and a high total serum vitamin D concentration of 243ng/ml (30-80ng/ml) as a result of daily consumption of prescribed 50,000IU ergocalciferol (vitamin D2) and 500mg calcium-citrate for 1y. Patient 2 was a 60-y old woman who consumed 40,000IU of cholecalciferol (vitamin D3) daily for >10months with a peak total serum vitamin D concentration of 479ng/ml (30-80ng/ml), but did not present with symptoms related to vitamin D toxicity. CONCLUSION: These cases demonstrate that individual responses to supraphysiologic concentrations of vitamin D for extended periods of time vary widely, and that defining a toxic concentration of this vitamin is difficult. The different outcomes in these two patients, despite months of high-dose vitamin D therapy, demonstrates that individual patient pharmacodynamics determine clinical sequelae.


Assuntos
Suplementos Nutricionais/efeitos adversos , Vitamina D/efeitos adversos , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Vitamina D/sangue
10.
Circ Cardiovasc Genet ; 10(2)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28360086

RESUMO

Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine-N-oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine.


Assuntos
Doenças Cardiovasculares , Metaboloma , Metabolômica/métodos , Microbiota , American Heart Association , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Humanos , Estados Unidos
11.
Nat Rev Nephrol ; 13(4): 241-257, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28239173

RESUMO

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/terapia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Humanos , Indução de Remissão
12.
Clin Toxicol (Phila) ; 55(1): 51-54, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27448790

RESUMO

BACKGROUND: In the last decade there has been a worldwide surge in the recreational abuse of novel psychoactive substances, particularly amphetamine derivatives and synthetic cannabinoids. Synthetic opioids such as AH-7921, MT-45, and U-47700, with structures distinct from those ever used therapeutically or described recreationally, have also recently emerged. CASE DETAILS: We report a patient who suffered respiratory failure and depressed level of consciousness after recreationally using a novel synthetic opioid labeled U-47700. A single dose of naloxone administered by paramedics completely reversed his opioid poisoning. Comprehensive laboratory analysis confirmed the presence of a novel synthetic opioid and excluded other drugs. The drug used appeared to have caused a false positive benzodiazepine result on the initial urine drugs of abuse panel. CONCLUSION: The case we describe of toxicity from the synthetic opioid labeled U-47700 highlights the emerging trend of novel synthetic opioid abuse.


Assuntos
Analgésicos Opioides/envenenamento , Benzamidas/envenenamento , Drogas Desenhadas/envenenamento , Insuficiência Respiratória/induzido quimicamente , Analgésicos Opioides/urina , Benzamidas/urina , Humanos , Masculino , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Detecção do Abuso de Substâncias/métodos , Adulto Jovem
13.
Clin Toxicol (Phila) ; 55(1): 73, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27744720
14.
J Bone Miner Res ; 31(10): 1841-1844, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27105398

RESUMO

The CYP24A1 gene encodes a mitochondrial 24-hydroxylase that inactivates 1,25(OH)2 D. Loss-of-function mutations in CYP24A1 cause hypercalcemia, nephrolithiasis and nephrocalcinosis. We describe a woman with CYP24A1 deficiency and recurrent gestational hypercalcemia. Her first pregnancy, at age 20, resulted with the intrauterine demise of twin fetuses. Postpartum, she developed severe hypercalcemia (14 mg/dL), altered mental status, and acute pancreatitis. Her PTH was suppressed (6 pg/mL) and her 1,25(OH)2 D was elevated (165 and 195 pg/mL on postpartum day 1 and 5, respectively). Between one and three months postpartum, her serum calcium decreased from 11.4 to 10.2 mg/dL while her 1,25(OH)2 D level decreased from 83 to 24 pg/mL. Her 24-hour urine calcium was 277 mg. Six months postpartum, she became pregnant again. At 14 weeks, her albumin-corrected calcium level was 10.4 mg/dL and her 1,25(OH)2 D level exceeded 200 pg/mL. To establish the diagnosis of CYP24A1 deficiency, we showed her 24,25(OH)2 D level to be undetectable (<2 ng/mL). Exon sequencing of the CYP24A1 gene revealed a homozygous, 8-nucleotide deletion in exon 8, causing an S334V substitution and premature termination due to a frame shift (c.999_1006del, p.Ser334Valfs*9). To prevent hypercalcemia, she was advised to discontinue prenatal vitamins, avoid sun exposure and calcium-rich foods, and start omeprazole and a calcium binder (250 mg K-Phos-neutral with meals). Despite these measures, both hypercalcemia (11.5 mg/dL) and acute pancreatitis recurred. Labor was induced and a healthy, normocalcemic boy was delivered. In the absence of lactation, maternal hypercalcemia resolved within 2 months. This report shows that CYP24A1-deficient subjects may be normocalcemic at baseline. Hypercalcemia may be unmasked by pregnancy through the routine use of calciferol-containing prenatal vitamins, increased 1-alpha hydroxylation of VitD by the placenta and maternal kidney, and production of PTHrP by the uteroplacental unit. CYP24A1 deficiency should be considered in patients with unexplained vitamin D-mediated hypercalcemia. © 2016 American Society for Bone and Mineral Research.


Assuntos
Sequência de Bases , Hipercalcemia , Pancreatite , Transtornos Puerperais , Deleção de Sequência , Vitamina D3 24-Hidroxilase/deficiência , Doença Aguda , Adulto , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/tratamento farmacológico , Hipercalcemia/genética , Pancreatite/sangue , Pancreatite/tratamento farmacológico , Pancreatite/genética , Gravidez , Transtornos Puerperais/sangue , Transtornos Puerperais/tratamento farmacológico , Transtornos Puerperais/genética
15.
J Anal Toxicol ; 40(4): 243-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26945835

RESUMO

Alternative specimens have been occasionally considered as substitutes for whole blood for postmortem toxicology testing. We studied the applicability of vitreous humor, and evaluated whether it would be suitable to replace (or augment) whole blood for routine drug screening. Results showed that from 51 autopsy cases, we were able to identify an aggregate of 209 findings in whole blood compared with 169 in vitreous. The total number of compounds identified was 71 for whole blood and 60 for vitreous humor. Quantitative analysis showed that whole-blood concentrations of trazodone were several fold higher than vitreous humor concentrations (1.42 ± 0.57 vs. 0.15 ± 0.05 mg/L, respectively) and similar results were also obtained for diazepam (0.37 ± 0.06 vs. 0.13 ± 0.01, respectively). For other drugs such as oxycodone, hydrocodone and doxylamine, a trend suggesting higher concentrations in vitreous humor vs. whole blood was observed; however, this was not significant. Our results are consistent with the limited work of other investigators, and suggest that vitreous humor could be an appropriate matrix for drug screening in postmortem toxicology.


Assuntos
Toxicologia Forense/métodos , Preparações Farmacêuticas/análise , Corpo Vítreo/química , Antidepressivos de Segunda Geração/análise , Autopsia , Análise Química do Sangue , Diazepam/análise , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias , Trazodona/análise
16.
Clin Chim Acta ; 455: 93-8, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26797672

RESUMO

BACKGROUND: Acute kidney injury (AKI) is associated with increased mortality, morbidity, hospital length of stay, and costs. A quantitative urine test is available to assess the risk of developing AKI by measuring the concentrations of two protein biomarkers, TIMP-2 and IGFBP-7. The NephroCheck Test combines these concentrations into an AKIRisk Score. The purpose of this study is to characterize the analytical performance characteristics of the AKIRisk Score. METHODS: Linearity and analytical sensitivity were evaluated by following Clinical Laboratory Standards Institute (CLSI) EP06-A and EP17-A, respectively. Precision was evaluated by testing clinical samples and examining the repeatability of test results. Potential interference was evaluated for endogenous and exogenous substances. Sample stability was examined at room temperature and at 2-8°C, as well as the effect of sample centrifugation temperature on test results. RESULTS: The AKIRisk Score exhibits approximately 10% coefficient of variation (CV) at the recommended cutoff value of 0.3 and the limit of quantitation (LoQ) was 0.002. Only albumin, bilirubin (conjugated), and methylene blue interfered with test results, at concentrations exceeding 1250 mg/L, 72 mg/L, and 0.49 mg/L, respectively. AKIRisk Score results were stable for 6h at room temperature, 24h refrigerated, and not impacted by sample centrifugation temperature. CONCLUSIONS: Our studies demonstrate that the AKIRisk Score has robust analytical performance, good precision, minimal analytical interference, acceptable sensitivity, and excellent sample stability.


Assuntos
Biomarcadores/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Nefropatias/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Doença Aguda , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Medição de Risco
17.
Clin Chim Acta ; 452: 32-7, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26522657

RESUMO

BACKGROUND: Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) have demonstrated significantly improved diagnostic performance in assessing risk for acute kidney injury (AKI) compared with existing biomarkers. We present the findings of a multi-site trial to determine the reference intervals for these biomarkers in apparently healthy adults and those with stable chronic morbid conditions without AKI. METHODS: A urine specimen was collected from apparently healthy subjects (N=378) and subjects with at least one stable chronic morbidity (N=372). Specimens were kept frozen until analysis with the NephroCheck® Test (Astute Medical). The test is comprised of fluorescence immunoassays for IGFBP7 and TIMP-2 and is used with the Astute140® Meter which quantifies the concentration of each biomarker. The meter multiplies the concentrations of IGFBP7 and TIMP-2 and displays the result as a numerical value ([IGFBP7]∙[TIMP-2]) expressed in (ng/ml)(2)/1000 which is called the AKIRisk™ Score. RESULTS: The reference intervals (inner 95%) for [IGFBP7]∙[TIMP-2] in all subjects (N=750), apparently healthy subjects, and subjects with stable chronic morbidities were 0.04-2.22, 0.04-2.25, and 0.05-2.20 (ng/ml)(2)/1000 respectively. There was no statistical difference between reference intervals for apparently healthy and chronic stable morbid cohorts (p=0.42). CONCLUSIONS: Our investigation showed that urine [IGFBP7]∙[TIMP-2] values were not elevated in patients with stable chronic morbidities who did not have AKI.


Assuntos
Lesão Renal Aguda/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Adulto , Idoso , Biomarcadores/urina , Doença Crônica , Feminino , Fluorescência , Voluntários Saudáveis , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Valores de Referência
18.
Clin Chem ; 62(1): 92-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26553795

RESUMO

BACKGROUND: Historically the success of mass spectrometry in the clinical laboratory has focused on drugs of abuse confirmations, newborn screening, and steroid analysis. Clinical applications of mass spectrometry continue to expand, and mass spectrometry is now being used in almost all areas of laboratory medicine. CONTENT: A brief background of the evolution of mass spectrometry in the clinical laboratory is provided with a discussion of future applications. Prominent examples of mass spectrometry are covered to illustrate how it has improved the practice of medicine and enabled physicians to provide better patient care. With increasing economic pressures and decreasing laboratory test reimbursement, mass spectrometry testing has been shown to provide cost-effective solutions. In addition to pointing out the numerous benefits, the challenges of implementing mass spectrometry in the clinical laboratory are also covered. SUMMARY: Mass spectrometry continues to play a prominent role in the field of laboratory medicine. The advancement of this technology along with the development of new applications will only accelerate the incorporation of mass spectrometry into more areas of medicine.


Assuntos
Técnicas de Laboratório Clínico , Espectrometria de Massas , Preparações Farmacêuticas/análise , Medicina Clínica , Humanos , Recém-Nascido , Triagem Neonatal , Esteroides/análise
19.
Ther Drug Monit ; 38(3): 300-4, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26473523

RESUMO

BACKGROUND: Tacrolimus (Prograf, Advagraf, and FK-506) is the most commonly prescribed calcineurin inhibitor after kidney and liver transplantation. The use of tacrolimus (in conjunction with other drugs) has successfully contributed to the maintenance of solid organ allografts; however, it also exhibits toxic side effects. Therapeutic drug monitoring of tacrolimus is used as an aid to achieve drug concentrations within a narrow therapeutic window. METHODS: The Waters MassTrak Immunosuppressants assay (LC-MS/MS) for the quantification of tacrolimus in whole blood was evaluated for precision, linearity, lower limit of quantification, matrix effects, and accuracy. A method comparison with the Abbott Architect Tacrolimus immunoassay was also performed. RESULTS: The mean concentration (nanograms per milliliter) and coefficient of variation for low, mid, and high patient pools were 0.6% ± 19.9%, 16.0% ± 5.4%, and 31.2% ± 5.8%, respectively. The MassTrak assay was linear from 0.5 to 30.0 ng/mL. Although the MassTrak and Architect assays correlated well (R = 0.97) for patient samples, the MassTrak assay displayed an average negative bias of 18.5% versus Architect (range of 0.0%-36.7%). Analysis of a certified tacrolimus reference material in human whole blood [European Reference Materials (ERM)-DA110a, LGC Standards] on both platforms failed to completely explain the observed difference for patient samples. CONCLUSIONS: Two widely used assays for therapeutic drug monitoring of tacrolimus are not in agreement with one another. Care should be exercised when interpreting results generated on these 2 assay platforms.


Assuntos
Cromatografia Líquida/métodos , Imunossupressores/farmacocinética , Tacrolimo/farmacocinética , Espectrometria de Massas em Tandem/métodos , Monitoramento de Medicamentos/métodos , Humanos , Imunoensaio/métodos , Limite de Detecção
20.
Data Brief ; 5: 888-92, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26702417

RESUMO

This data in brief describes characteristics of chronic stable comorbid patients who were included in reference range studies of [IGFBP7]·[TIMP-2] "Reference Intervals of Urinary Acute Kidney Injury (AKI) Markers [IGFBP7]·[TIMP2] in Apparently Healthy Subjects and Chronic Comorbid Subjects without AKI" [1]. In order to determine the specificity of [IGFBP7]·[TIMP-2] for identifying patients at risk of developing AKI we studied a cohort with nine broad classification of disease who did not have AKI. Details regarding the population that was targeted for inclusion in the study are also described. Finally, we present data on the inclusion criteria for the healthy subjects used in this investigation to determine the reference range.

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