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1.
Cancer Epidemiol Biomarkers Prev ; 29(3): 643-649, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32102909

RESUMO

BACKGROUND: A mandated reduction in the nicotine content of cigarettes could reduce smoking rate and prevalence. However, one concern is that smokers may compensate by increasing the intensity with which they smoke each cigarette to obtain more nicotine. This study assessed whether smokers engage in compensatory smoking by estimating the mouth-level nicotine intake of low nicotine cigarettes smoked during a clinical trial. METHODS: Smokers were randomly assigned to receive cigarettes with one of five nicotine contents for 6 weeks. An additional group received a cigarette with the lowest nicotine content, but an increased tar yield. The obtained mouth-level nicotine intake from discarded cigarette butts for a subset of participants (51-70/group) was estimated using solanesol as described previously. A compensation index was calculated for each group to estimate the proportion of nicotine per cigarette recovered through changes in smoking intensity. RESULTS: There was no significant increase in smoking intensity for any of the reduced nicotine cigarettes as measured by the compensation index (an estimated 0.4% of the nicotine lost was recovered in the lowest nicotine group; 95% confidence interval, -0.1 to 1.2). There was a significant decrease in smoking intensity for very low nicotine content cigarettes with increased tar yield. CONCLUSIONS: Reductions in nicotine content did not result in compensatory changes in how intensively participants smoked research cigarettes. IMPACT: Combined with data from clinical trials showing a reduction in cigarettes smoked per day, these data suggest that a reduction in nicotine content is unlikely to result in increased smoke exposure.

2.
Perit Dial Int ; 40(2): 185-192, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063191

RESUMO

BACKGROUND: Peritoneal dialysis (PD) is a more cost-effective therapy to treat kidney failure than in-center hemodialysis, but successful therapy requires a functioning PD catheter that causes minimal complications. In 2015, the North American Chapter of the International Society for Peritoneal Dialysis established the North American PD Catheter Registry to improve practices and patient outcomes following PD catheter insertion. AIMS: The objective of this study is to propose a methodology for defining insertion-related complications that lead to significant adverse events and report the risk of these complications among patients undergoing laparoscopic PD catheter insertion. METHODS: Patients undergoing laparoscopic PD catheter insertion were enrolled at 14 participating centers in Canada and the United States and followed using a Web-based registry. Insertion-related complications were defined as flow restriction, exit-site leak, or abdominal pain at any point during follow-up. We also included infections or bleeding within 30 days of insertion, and any immediate postoperative complications. Adverse events were categorized as PD never starting or termination of PD therapy, delay in the start of PD therapy or interruption of PD therapy, an emergency department visit or hospitalization, or need for invasive procedures. Cause-specific cumulative incidence functions were used to estimate risk. RESULTS: Five hundred patients underwent laparoscopic PD catheter insertion between 10 November 2015 and 24 July 2018. The cumulative risk of insertion-related complications 6 months from the date of insertion that led to an adverse event was 24%. The risk of flow restriction, exit-site leak, and pain at 6 months was 10.2%, 5.7%, and 5.3%, respectively. PD was never started or terminated in 6.4% of patients due to an insertion-related complication. Leaks and flow restrictions were most likely to delay or interrupt PD therapy. Flow restrictions were the primary cause of invasive procedures. Fifty percent of the complications occurred before the start of PD therapy. CONCLUSIONS: Insertion-related complications leading to significant adverse events following laparoscopic placement of PD catheters are common. Many complications occur before the start of PD. Insertion-related complications are an important area of focus for future research and quality improvement efforts.

4.
N Engl J Med ; 382(8): 697-705, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31860793

RESUMO

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).


Assuntos
Lesão Pulmonar Aguda/patologia , Líquido da Lavagem Broncoalveolar/química , Sistemas Eletrônicos de Liberação de Nicotina , Vaping/efeitos adversos , Vitamina E/análise , Lesão Pulmonar Aguda/etiologia , Adolescente , Adulto , Idoso , Fumar Cigarros , Óleo de Coco/análise , Feminino , Humanos , Limoneno/análise , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
5.
MMWR Morb Mortal Wkly Rep ; 68(45): 1040-1041, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31725707

RESUMO

CDC, the Food and Drug Administration (FDA), state and local health departments, and multiple public health and clinical partners are investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). Based on data collected as of October 15, 2019, 86% of 867 EVALI patients reported using tetrahydrocannabinol (THC)-containing products in the 3 months preceding symptom onset (1). Analyses of THC-containing product samples by FDA and state public health laboratories have identified potentially harmful constituents in these products, such as vitamin E acetate, medium chain triglyceride oil (MCT oil), and other lipids (2,3) (personal communication, D.T. Heitkemper, FDA Forensic Chemistry Center, November 2019). Vitamin E acetate, in particular, might be used as an additive in the production of e-cigarette, or vaping, products; it also can be used as a thickening agent in THC products (4). Inhalation of vitamin E acetate might impair lung function (5-7).


Assuntos
Líquido da Lavagem Broncoalveolar/química , Surtos de Doenças , Lesão Pulmonar/epidemiologia , Vaping/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
6.
Toxicol Lett ; 317: 53-58, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31560942

RESUMO

In 2017, the U.S. Department of Health and Human Services and the White House declared a public health emergency to address the opioid crisis (Hargan, 2017). On average, 192 Americans died from drug overdoses each day in 2017; 130 (67%) of those died specifically because of opioids (Scholl et al., 2019). Since 2013, there have been significant increases in overdose deaths involving synthetic opioids - particularly those involving illicitly-manufactured fentanyl. The U.S. Drug Enforcement Administration (DEA) estimates that 75% of all opioid identifications are illicit fentanyls (DEA, 2018b). Laboratories are routinely asked to confirm which fentanyl or other opioids are involved in an overdose or encountered by first responders. It is critical to identify and classify the types of drugs involved in an overdose, how often they are involved, and how that involvement may change over time. Health care providers, public health professionals, and law enforcement officers need to know which opioids are in use to treat, monitor, and investigate fatal and non-fatal overdoses. By knowing which drugs are present, appropriate prevention and response activities can be implemented. Laboratory testing is available for clinically used and widely recognized opioids. However, there has been a rapid expansion in new illicit opioids, particularly fentanyl analogs that may not be addressed by current laboratory capabilities. In order to test for these new opioids, laboratories require reference standards for the large number of possible fentanyls. To address this need, the Centers for Disease Control and Prevention (CDC) developed the Traceable Opioid Material§ Kits product line, which provides over 150 opioid reference standards, including over 100 fentanyl analogs. These kits were designed to dramatically increase laboratory capability to confirm which opioids are on the streets and causing deaths. The kits are free to U.S based laboratories in the public, private, clinical, law enforcement, research, and public health domains.


Assuntos
Analgésicos Opioides/análise , Overdose de Drogas/diagnóstico , Fentanila/análise , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Kit de Reagentes para Diagnóstico/normas , Detecção do Abuso de Substâncias/normas , Analgésicos Opioides/classificação , Calibragem , Overdose de Drogas/mortalidade , Fentanila/análogos & derivados , Fentanila/classificação , Humanos , Transtornos Relacionados ao Uso de Opioides/mortalidade , Valor Preditivo dos Testes , Padrões de Referência , Reprodutibilidade dos Testes , Estados Unidos/epidemiologia
7.
J Intensive Care Med ; : 885066619865469, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31342846

RESUMO

OBJECTIVE: Hyperchloremia is associated with worsened outcomes in various clinical situations; however, data are limited in patients with diabetic ketoacidosis (DKA). The purpose of this study was to determine the effect of hyperchloremia on time to DKA resolution. METHODS: We conducted a retrospective cohort study of adult patients admitted with incident DKA from January 2013 through October 2017 and stratified by the development of hyperchloremia versus maintaining normochloremia. The primary outcome was time to final DKA resolution. Secondary outcomes included time to initial DKA resolution, incidence of acute kidney injury (AKI) on admission, in-hospital development of AKI, and hospital length of stay (LOS). RESULTS: Of the 102 patients included, 52 developed hyperchloremia. Patients with hyperchloremia had longer times to final DKA resolution compared to those with normochloremia (median 22.3 [interquartile range, IQR, 15.2-36.9] vs 14.2 [IQR 8.8-21.1] hours; P = .001). Time to initial DKA resolution was also longer in patients who developed hyperchloremia compared to those who did not (median 16.3 vs 10.9 hours; P = .024). More patients with hyperchloremia developed in-hospital AKI (26.9% vs 8.0%; P = .01). Median hospital LOS was significantly longer in the hyperchloremia cohort (P < .001). On Cox regression analysis, time to DKA resolution was significantly longer with each 1 mmol/L increase in serum chloride (HR 0.951; P < .001). CONCLUSION: The presence of hyperchloremia in patients with DKA was associated with increased time to DKA resolution, risk of in-hospital AKI, and hospital LOS. Further evaluation of the avoidance or treatment of hyperchloremia in DKA is needed.

8.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1118-1119: 137-147, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31035135

RESUMO

Progress toward better diagnosis and treatment of lipid metabolism-related diseases requires high throughput approaches for multiplexed quantitative analysis of structurally diverse lipids, including phospholipids (PLs). This work demonstrates a simplified "one-pot" phospholipid extraction protocol, as an alternative to conventional liquid-liquid extraction. Performed in a 96-well format, the extraction was coupled with high throughput UPLC and multiplexed tandem mass spectrometry (MS/MS) detection, allowing non-targeted quantification of phosphatidylcholines (PC), sphingomyelins (SM), lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE), and phosphatidylinositols (PI). Using 50 µL aliquots of serum samples from 110 individuals, lipoproteins were fractionated by size, and analyzed for phospholipids and non-polar lipids including free cholesterol (FC), cholesteryl esters (CEs) and triglycerides (TGs). Analysis of serum samples with wide range of Total-TG levels showed significant differences in PL composition. The correlations of molar ratios in lipoprotein size fractions, SM/PL with FC/PL, PE/PL with TG/CE, and PE/PL with PI/PL, demonstrate the applicability of the method for quantitative composition analysis of high, low and very-low density lipoproteins (HDL, LDL and VLDL), and characterization of lipid metabolism related disease states.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Fosfolipídeos/sangue , Espectrometria de Massas em Tandem/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Fosfolipídeos/isolamento & purificação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-30056267

RESUMO

Hypoglycin A (HGA) and methylenecyclopropylglycine (MCPG) are naturally-occurring amino acids known to cause hypoglycemia and encephalopathy. Exposure to one or both toxins through the ingestion of common soapberry (Sapindaceae) fruits are documented in illness outbreaks throughout the world. Jamaican Vomiting Sickness (JVS) and seasonal pasture myopathy (SPM, horses) are linked to HGA exposure from unripe ackee fruit and box elder seeds, respectively. Acute toxic encephalopathy is linked to HGA and MCPG exposures from litchi fruit. HGA and MCPG are found in several fruits within the soapberry family and are known to cause severe hypoglycemia, seizures, and death. HGA has been directly quantified in horse blood in SPM cases and in human gastric juice in JVS cases. This work presents a new diagnostic assay capable of simultaneous quantification of HGA and MCPG in human plasma, and it can be used to detect patients with toxicity from soapberry fruits. The assay presented herein is the first quantitative method for MCPG in blood matrices.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ciclopropanos/sangue , Glicina/análogos & derivados , Hipoglicinas/sangue , Espectrometria de Massas em Tandem/métodos , Glicina/sangue , Humanos , Limite de Detecção , Modelos Lineares , Intoxicação por Plantas , Reprodutibilidade dos Testes , Sapindaceae
10.
Food Chem ; 264: 449-454, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29853400

RESUMO

Methylenecyclcopropylglycine (MCPG) and hypoglycin A (HGA) are naturally occurring amino acids found in various soapberry (Sapindaceae) fruits. These toxins have been linked to illnesses worldwide and were recently implicated in Asian outbreaks of acute hypoglycemic encephalopathy. In a previous joint agricultural and public health investigation, we developed an analytical method capable of evaluating MCPG and HGA concentrations in soapberry fruit arils as well as a clinical method for the urinary metabolites of the toxins. Since the initial soapberry method only analyzed the aril portion of the fruit, we present here the extension of the method to include the fruit seed matrix. This work is the first method to quantitate both MCPG and HGA concentrations in the seeds of soapberry fruit, including those collected during a public health investigation. Further, this is the first quantitation of HGA in litchi seeds as well as both toxins in mamoncillo and longan seeds.


Assuntos
Cromatografia Líquida de Alta Pressão , Ciclopropanos/análise , Glicina/análogos & derivados , Hipoglicinas/análise , Sapindus/metabolismo , Espectrometria de Massas em Tandem , Frutas/química , Frutas/metabolismo , Glicina/análise , Sementes/metabolismo
11.
Cancer Epidemiol Biomarkers Prev ; 27(9): 1083-1090, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29853481

RESUMO

Background: Biomarkers of tobacco exposure have a central role in studies of tobacco use and nicotine intake. The most significant exposure markers are nicotine itself and its metabolites in urine. Therefore, it is important to evaluate the performance of laboratories conducting these biomarker measurements.Methods: This report presents the results from a method performance study involving 11 laboratories from 6 countries that are currently active in this area. Each laboratory assayed blind replicates of seven human urine pools at various concentrations on three separate days. The samples included five pools blended from smoker and nonsmoker urine sources, and two additional blank urine samples fortified with pure nicotine, cotinine, and hydroxycotinine standards. All laboratories used their own methods, and all were based on some form of liquid chromatography/tandem mass spectrometry.Results: Overall, good agreement was found among the laboratories in this study. Intralaboratory precision was good, and in the fortified pools, the mean bias observed was < + 3.5% for nicotine, approximately 1.2% for hydroxycotinine, and less than 1% for cotinine (1 outlier excluded in each case). Both indirect and direct methods for analyzing the glucuronides gave comparable results.Conclusions: This evaluation indicates that the experienced laboratories participating in this study can produce reliable and comparable human urinary nicotine metabolic profiles in samples from people with significant recent exposure to nicotine.Impact: This work supports the reliability and agreement of an international group of established laboratories measuring nicotine and its metabolites in urine in support of nicotine exposure studies. Cancer Epidemiol Biomarkers Prev; 27(9); 1083-90. ©2018 AACR.


Assuntos
Biomarcadores/urina , Cotinina/análogos & derivados , Glucuronídeos/urina , Nicotina/urina , Fumar/epidemiologia , Fumar/urina , Cotinina/urina , Humanos , Valor Preditivo dos Testes , Prevalência , Reprodutibilidade dos Testes , Estados Unidos/epidemiologia
12.
PLoS One ; 13(4): e0194797, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29634782

RESUMO

Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples.


Assuntos
Apolipoproteínas/sangue , Cromatografia Líquida/métodos , Fracionamento por Campo e Fluxo/métodos , Lipídeos/sangue , Lipoproteínas/sangue , Espectrometria de Massas em Tandem/métodos , Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Análise Química do Sangue/métodos , Calibragem , Colesterol/química , Humanos , Luz , Modelos Estatísticos , Tamanho da Partícula , Controle de Qualidade , Espalhamento de Radiação , Fluxo de Trabalho
13.
Hemodial Int ; 22(2): 270-278, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28643378

RESUMO

INTRODUCTION: High ultrafiltration (UF) rates can result in intradialytic hypotension and are associated with increased mortality. The effects of a weight-based UF rate limit on intradialytic hypotension and the potential for unwanted fluid weight gain and hospitalizations for volume overload are unknown. METHODS: This retrospective cohort study examined 123 in-center hemodialysis patients at one facility who transitioned to 13 mL/kg/h maximum UF rates. Patients were studied for an 8 week UF rate limit exposure period and compared to the 8-week period immediately prior, during which the cohort served as its own historical control. The primary outcomes were frequency of intradialytic hypotension events and percentage of treatments with a hypotension event. FINDINGS: The delivered UF rate was lower during the exposure compared to the baseline period (mean UF rate 7.90 ± 4.45 mL/kg/h vs. 8.92 ± 5.64 mL/kg/h; P = 0.0005). The risk of intradialytic hypotension was decreased during the exposure compared to baseline period (event rate per treatment 0.0569 vs. 0.0719, OR 0.78 [95% CI 0.62-1.00]; P = 0.0474), as was the risk of having a treatment with a hypotension event (percentage of treatments with event 5.2% vs. 6.8%, OR 0.75 [95% CI 0.58-0.96]; P = 0.0217). Subgroup analyses demonstrated that these findings were attributable to patients with high baseline UF rates. Statistically significant differences in all-cause or volume overload-related hospitalization were not observed during the exposure period. DISCUSSION: A weight-based UF rate limit of 13 mL/kg/h was associated with a decrease in the rate of intradialytic hypotension events among in-center hemodialysis patients.


Assuntos
Hipotensão/fisiopatologia , Diálise Renal/métodos , Ultrafiltração/métodos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Am Soc Mass Spectrom ; 28(11): 2319-2329, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801822

RESUMO

We demonstrate the application of in-source nitrogen collision-induced dissociation (CID) that eliminates the need for ester hydrolysis before simultaneous analysis of esterified cholesterol (EC) and triglycerides (TG) along with free cholesterol (FC) from human serum, using normal phase liquid chromatography (LC) coupled to atmospheric pressure chemical ionization (APCI) tandem mass spectrometry (MS/MS). The analysis requires only 50 µL of 1:100 dilute serum with a high-throughput, precipitation/evaporation/extraction protocol in one pot. Known representative mixtures of EC and TG species were used as calibrators with stable isotope labeled analogs as internal standards. The APCI MS source was operated with nitrogen source gas. Reproducible in-source CID was achieved with the use of optimal cone voltage (declustering potential), generating FC, EC, and TG lipid class-specific precursor fragment ions for multiple reaction monitoring (MRM). Using a representative mixture of purified FC, CE, and TG species as calibrators, the method accuracy was assessed with analysis of five inter-laboratory standardization materials, showing -10% bias for Total-C and -3% for Total-TG. Repeated duplicate analysis of a quality control pool showed intra-day and inter-day variation of 5% and 5.8% for FC, 5.2% and 8.5% for Total-C, and 4.1% and 7.7% for Total-TG. The applicability of the method was demonstrated on 32 serum samples and corresponding lipoprotein sub-fractions collected from normolipidemic, hypercholesterolemic, hypertriglyceridemic, and hyperlipidemic donors. The results show that in-source CID coupled with isotope dilution UHPLC-MS/MS is a viable high precision approach for translational research studies where samples are substantially diluted or the amounts of archived samples are limited. Graphical Abstract ᅟ.


Assuntos
Colesterol/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Triglicerídeos/sangue , Ésteres do Colesterol/sangue , Humanos , Hidrólise , Reprodutibilidade dos Testes
15.
Am J Clin Nutr ; 105(5): 1063-1069, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28381474

RESUMO

Background: The consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular disease, and reducing their consumption is a major public health objective. Food intake studies have provided estimates for TFA concentrations in the US population; however, there is a need for data on TFA blood concentrations in the population.Objective: The objective of this study was to determine plasma TFA concentrations in a nationally representative group of fasted adults in the US population in NHANES samples from 1999-2000 and 2009-2010.Design: Four major TFAs [palmitelaidic acid (C16:1n-7t), trans vaccenic acid (C18:1n-7t), elaidic acid (C18:1n-9t), and linoelaidic acid (C18:2n-6t,9t)] were measured in plasma in 1613 subjects from NHANES 1999-2000 and 2462 subjects from NHANES 2009-2010 by gas chromatography-mass spectrometry. Geometric means and distribution percentiles were calculated for each TFA and their sum by age, sex, and race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American), and covariate-adjusted geometric means were computed by using a model that included these demographic and other dietary factors, as well as survey year and any significant interaction terms.Results: These nationally representative data for the adult US population show that TFA concentrations were 54% lower in NHANES 2009-2010 than in NHANES 1999-2000. Covariate-adjusted geometric means for the sum of the 4 TFAs were 81.4 µmol/L (95% CI: 77.3, 85.6 µmol/L) and 37.8 µmol/L (95% CI: 36.4, 39.4 µmol/L) in NHANES 1999-2000 and 2009-2010, respectively. Even with the large decline in TFA concentrations, differences between demographic subgroups were comparable in the 2 surveys.Conclusion: The results indicate an overall reduction in TFA concentrations in the US population and provide a valuable baseline to evaluate the impact of the recent regulation categorizing TFAs as food additives.


Assuntos
Gorduras na Dieta/sangue , Jejum , Estado Nutricional , Ácidos Graxos Trans/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Dieta , Comportamento Alimentar , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidrogenação , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de Risco , Estados Unidos , Adulto Jovem
16.
Proteomics Clin Appl ; 11(7-8)2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28296203

RESUMO

PURPOSE: Apolipoprotein A-I (ApoA-I) and apolipoprotein B-100 (ApoB-100) are amphipathic proteins that are strong predictors of cardiovascular disease risk. The traceable calibration of apolipoprotein assays is a persistent challenge, especially for ApoB-100, which cannot be solubilized in purified form. EXPERIMENTAL DESIGN: A simultaneous quantitation method for ApoA-I and ApoB-100 was developed using tryptic digestion without predigestion reduction and alkylation, followed by LC separation coupled with isotope dilution MS analysis. The accuracy of the method was assured by selecting structurally exposed signature peptides, optimal choice of detergent, protein:enzyme ratio, and incubation time. Peptide calibrators were value assigned by isobaric tagging isotope dilution MS amino acid analysis. RESULTS: The method reproducibility was validated in technical repeats of three serum samples, giving 2-3% intraday CVs (N = 5) and <7% interday CVs (N = 21). The repeated analysis of interlaboratory harmonization standards showed -1% difference for ApoA-I and -12% for ApoB-100 relative to the assigned value. The applicability of the method was demonstrated by repeated analysis of 24 patient samples with a wide range of total cholesterol and triglyceride levels. CONCLUSIONS AND CLINICAL RELEVANCE: The method is applicable for simultaneous analysis of ApoA-I and ApoB-100 in patient samples, and for characterization of serum pool calibrators for other analytical platforms.


Assuntos
Apolipoproteína A-I/química , Apolipoproteína B-100/química , Análise Química do Sangue/métodos , Espectrometria de Massas , Fragmentos de Peptídeos/sangue , Proteólise , Tripsina/metabolismo , Sequência de Aminoácidos , Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Calibragem , Cromatografia Líquida , Humanos , Isótopos/química , Modelos Lineares , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Reprodutibilidade dos Testes
17.
Lancet Glob Health ; 5(4): e458-e466, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28153514

RESUMO

BACKGROUND: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 - 24]) and absence of an evening meal (2·2 [1·2-4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3-18·8], without evening meal; OR 3·6 [1·1-11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 µg/g to 152·0 µg/g and MCPG ranged from 44·9 µg/g to 220·0 µg/g. INTERPRETATION: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING: US Centers for Disease Control and Prevention.


Assuntos
Encefalopatia Aguda Febril/diagnóstico , Surtos de Doenças/estatística & dados numéricos , Frutas/toxicidade , Litchi/toxicidade , Síndromes Neurotóxicas/diagnóstico , Encefalopatia Aguda Febril/epidemiologia , Encefalopatia Aguda Febril/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Ciclopropanos/análise , Feminino , Glicina/análogos & derivados , Glicina/análise , Humanos , Hipoglicinas/análise , Índia , Masculino , Síndromes Neurotóxicas/epidemiologia , Síndromes Neurotóxicas/etiologia , Razão de Chances
18.
J Proteomics ; 150: 258-267, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-27667389

RESUMO

Apolipoproteins measured in plasma or serum are potential biomarkers for assessing metabolic irregularities that are associated with the development of cardiovascular disease (CVD). LC-MS/MS allows quantitative measurement of multiple apolipoproteins in the same sample run. However, the accuracy and precision of the LC-MS/MS measurement depends on the reproducibility of the enzymatic protein digestion step. With the application of an immobilized enzyme reactor (IMER), the reproducibility of the trypsin digestion can be controlled with high precision via flow rate, column volume and temperature. In this report, we demonstrate the application of an integrated IMER-LC-MS/MS platform for the simultaneous quantitative analysis of eight apolipoproteins. Using a dilution series of a characterized serum pool as calibrator, the method was validated by repeated analysis of pooled sera and individual serum samples with a wide range of lipid profiles, all showing intra-assay CV<4.4% and inter-assay CV<8%. In addition, the method was compared with traditional homogeneous digestion coupled LC-MS/MS for the quantification of apoA-I and apoB-100. Applied in large scale human population studies, this method can serve the translation of a wider panel of apolipoprotein biomarkers from research to clinical application. SIGNIFICANCE: Currently, the translation of apolipoprotein biomarkers to clinical application is impaired because of the high cost of large cohort studies using traditional single-analyte immunoassays. The application of on-line tryptic digestion coupled with LC-MS/MS analysis is an effective way to address this problem. In this work we demonstrate a high throughput, multiplexed, automated proteomics workflow for the simultaneous analysis of multiple proteins.


Assuntos
Apolipoproteínas/análise , Proteólise , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Tripsina/metabolismo , Apolipoproteínas/metabolismo , Biomarcadores/sangue , Análise Química do Sangue/métodos , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo , Cromatografia Líquida , Estudos de Viabilidade , Humanos , Reprodutibilidade dos Testes
19.
Case Rep Nephrol Dial ; 7(3): 172-177, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29594144

RESUMO

This case describes an obese adult male peritoneal dialysis patient who presented with a pruritic follicular rash. Nutrient deficiency was not suspected initially in this case because there was no history of protein-calorie malnutrition, but the patient reported a diet devoid of fruits and vegetables and had not been taking his dialysis vitamin as prescribed. Skin biopsy showed follicular hyperkeratosis with fragmented hair shafts and corkscrew hairs consistent with scurvy. After supplementation with ascorbic acid 500 mg twice daily for 2 weeks, the rash resolved completely. Dialysis patients are at increased risk for vitamin C deficiency due to indiscriminant clearance of the nutrient with dialysis, but scurvy is rarely seen.

20.
J Agric Food Chem ; 64(27): 5607-13, 2016 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-27367968

RESUMO

Methylenecyclopropylglycine (MCPG) and hypoglycin A (HGA) are naturally occurring amino acids found in some soapberry fruits. Fatalities have been reported worldwide as a result of HGA ingestion, and exposure to MCPG has been implicated recently in the Asian outbreaks of hypoglycemic encephalopathy. In response to an outbreak linked to soapberry ingestion, the authors developed the first method to simultaneously quantify MCPG and HGA in soapberry fruits from 1 to 10 000 ppm of both toxins in dried fruit aril. Further, this is the first report of HGA in litchi, longan, and mamoncillo arils. This method is presented to specifically address the laboratory needs of public-health investigators in the hypoglycemic encephalitis outbreaks linked to soapberry fruit ingestion.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ciclopropanos/análise , Frutas/química , Glicina/análogos & derivados , Hipoglicinas/análise , Sapindaceae/química , Espectrometria de Massas em Tandem/métodos , Ciclopropanos/toxicidade , Frutas/toxicidade , Glicina/análise , Glicina/toxicidade , Hipoglicinas/toxicidade , Sapindaceae/toxicidade
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