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1.
Kidney Int ; 97(3): 477-486, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32001066

RESUMO

With the increasing availability of linked electronic health records, long-running cohorts, and high-throughput technologies, the potential for epidemiology research to improve the care of patients with kidney disease is greater than ever before. In this review, we highlight the application of epidemiology techniques to identify, evaluate, and address chronic kidney disease. We discuss studies that inform guidelines, identify health disparities, evaluate the genetic basis of disease, and relate data on omics, such as proteomics, metabolomics, and genetics, to outcomes. We describe how observational data have been used to facilitate the conduct of randomized controlled trials through enhanced identification of high-risk individuals and the evaluation of surrogate kidney disease outcomes as well as to address clinical questions where randomized controlled trials are impractical or infeasible. Finally, we discuss consumer engagement in research, including that of patients, policymakers, payers, and health care system, and the role of kidney disease epidemiology research in implementation science and as a key source of data and methodology for precision medicine.

2.
Mayo Clin Proc ; 94(11): 2220-2229, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31619367

RESUMO

OBJECTIVE: To assess the patterns of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARB) discontinuation in the setting of chronic kidney disease (CKD) progression in real-world clinical practice. PATIENTS AND METHODS: We identified incident ACE-I/ARB users with a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and without end-stage renal disease in the Geisinger Health System between January 1, 2004, and December 31, 2015. We investigated the associations of CKD stage, hospitalizations with and without acute kidney injury (AKI), serum potassium, bicarbonate level, thiazide, and loop diuretic use with ACE-I/ARB discontinuation. RESULTS: Among the 53,912 ACE-I/ARB users, the mean age was 59.9 years, and 50.6% were female. More than half of users discontinued ACE-I/ARB within 5 years of therapy initiation. The risk of ACE-I/ARB discontinuation increased with more advanced CKD stage. For example, patients who initiated ACE-I/ARB with CKD stage G4 (eGFR: 15-29 mL/min/1.73 m2) were 2.09-fold (95% CI, 1.87-2.34) more likely to discontinue therapy than those with eGFR ≥ 90 mL/min/1.73 m2. Potassium level greater than 5.3 mEq/L, systolic blood pressure ≤ 90 mm Hg, bicarbonate level < 22 mmol/L, and intervening hospitalization-particularly AKI-related-were also strong risk factors for ACE-I/ARB discontinuation. Thiazide diuretic use was associated with lower risk, whereas loop diuretic use was associated with higher risk of discontinuation. CONCLUSION: In a real-world cohort, discontinuation of ACE-I/ARB was common, particularly in patients with lower eGFR. Hyperkalemia, hypotension, low bicarbonate level, and hospitalization (AKI-related, in particular) were associated with a higher risk of ACE-I/ARB discontinuation. Additional studies are needed to evaluate the risk-benefit balance of discontinuing ACE-I/ARB in the setting of CKD progression.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Adesão à Medicação , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
4.
Clin J Am Soc Nephrol ; 14(3): 342-353, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30733224

RESUMO

BACKGROUND AND OBJECTIVES: Data are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria with serum metabolites identified using untargeted profiling in populations with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using stored serum samples from the African American Study of Kidney Disease and Hypertension (AASK; n=962) and the Modification of Diet in Renal Disease (MDRD) study (n=620), two rigorously conducted clinical trials with per-protocol measures of 24-hour proteinuria and GFR, we evaluated cross-sectional associations between urine protein-to-creatinine ratio and 637 known, nondrug metabolites, adjusting for key clinical covariables. Metabolites significantly associated with proteinuria were tested for associations with CKD progression. RESULTS: In the AASK and the MDRD study, respectively, the median urine protein-to-creatinine ratio was 80 (interquartile range [IQR], 28-359) and 188 (IQR, 54-894) mg/g, mean age was 56 and 52 years, 39% and 38% were women, 100% and 7% were black, and median measured GFR was 48 (IQR, 35-57) and 28 (IQR, 18-39) ml/min per 1.73 m2. Linear regression identified 66 serum metabolites associated with proteinuria in one or both studies after Bonferroni correction (P<7.8×10-5), 58 of which were statistically significant in a meta-analysis (P<7.8×10-4). The metabolites with the lowest P values (P<10-27) were 4-hydroxychlorthalonil and 1,5-anhydroglucitol; all six quantified metabolites in the phosphatidylethanolamine pathway were also significant. Of the 58 metabolites associated with proteinuria, four were associated with ESKD in both the AASK and the MDRD study. CONCLUSIONS: We identified 58 serum metabolites with cross-sectional associations with proteinuria, some of which were also associated with CKD progression. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_02_07_CJASNPodcast_19_03_.mp3.

5.
Clin J Am Soc Nephrol ; 13(7): 1013-1021, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29903900

RESUMO

BACKGROUND AND OBJECTIVES: Black Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death. RESULTS: At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02). CONCLUSIONS: Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.


Assuntos
Afro-Americanos , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Insuficiência Renal Crônica/sangue , Apolipoproteína L1/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Resuscitation ; 121: 1-8, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28943123

RESUMO

BACKGROUND: There remains controversy over the prognostic significance of spontaneous shockable rhythm conversion in out-of-hospital cardiac arrest (OHCA) patients with initial non-shockable heart rhythms (pulseless electrical activity [PEA] or asystole). The aim of this study was to examine the association of shockable rhythm conversion with multiple OHCA outcomes, and to explore effect modifiers. METHODS: A dual-reviewer search was conducted in PubMed and EMBASE databases in March 2017. Data on study design, patient characteristics, outcomes, adjusting and stratifying variables were extracted. Estimates were combined using random-effects models. RESULTS: Twelve studies involving 1,108,281 OHCA patients with initial non-shockable heart rhythms were identified using pre-specified eligibility criteria. Combined adjusted estimates showed that shockable rhythm conversion was associated with higher odds of pre-hospital return of spontaneous circulation (ROSC) (odds ratio [OR]=1.47, 95% confidence interval [CI] 1.40-1.55). Although shockable rhythm conversion was not associated with survival to hospital discharge (OR=1.36, 95% CI 0.77-2.38), it was associated with higher odds of one-month survival (OR=1.96, 95% CI 1.66-2.31), and one-month favourable neurological outcome (OR=2.69, 95% CI 2.00-3.62). Subgroup analyses found that shockable rhythm conversion from asystole, but not PEA, was associated with pre-hospital ROSC and survival to hospital discharge, and that earlier shockable rhythm conversions, compared to those occurring later during cardiopulmonary resuscitation, were associated with higher odds of one-month favourable neurological outcome. CONCLUSION: Shockable rhythm conversion from initial non-shockable heart rhythms was associated with better OHCA outcomes, depending on the type of initial heart rhythm, and time of rhythm conversion.


Assuntos
Reanimação Cardiopulmonar/mortalidade , Cardioversão Elétrica/mortalidade , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/métodos , Serviços Médicos de Emergência , Feminino , Frequência Cardíaca , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Estudos Prospectivos , Fatores de Tempo
8.
Clin Sci (Lond) ; 130(22): 2029-2042, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27729472

RESUMO

The discovery of endothelial progenitor cells (EPCs), a group of cells that play important roles in angiogenesis and the maintenance of vascular endothelial integrity, has led to considerable improvements in our understanding of the circulatory system and the regulatory mechanisms of vascular homoeostasis. Despite lingering disputes over where EPCs actually originate and how they facilitate angiogenesis, extensive research in the past decade has brought about significant advancements in this field of research, establishing EPCs as an essential element in the pathogenesis of various diseases. EPC and hypertensive disorders, especially essential hypertension (EH, also known as primary hypertension), represent one of the most appealing branches in this area of research. Chronic hypertension remains a major threat to public health, and the exact pathologic mechanisms of EH have never been fully elucidated. Is there a relationship between EPC and hypertension? If so, what is the nature of such relationship-is it mediated by blood pressure alterations, or other factors that lie in between? How can our current knowledge about EPCs be utilized to advance the prevention and clinical management of hypertension? In this review, we set out to answer these questions by summarizing the current concepts about EPC pathophysiology in the context of hypertension, while attempting to point out directions for future research on this subject.


Assuntos
Células Progenitoras Endoteliais/patologia , Hipertensão/patologia , Animais , Pressão Sanguínea , Células Progenitoras Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia
9.
Resuscitation ; 107: 88-93, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27554946

RESUMO

BACKGROUND: The prognostic implication of conversion from initially non-shockable to shockable rhythms in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. Our objective is to determine whether the conversion to shockable rhythms is a reliable predictor of short- and long-term outcomes both in patients who initially presented with pulseless electrical activity (PEA) and in those with asystole. METHODS: A secondary analysis was performed on non-traumatic OHCA cases ≥18 years old with PEA or asystole as initial rhythms, who were treated in the field and enrolled in the Resuscitation Outcomes Consortium (ROC) PRIMED study (clinicaltrials.gov/ct2/show/NCT00394706). We reported the characteristics and outcomes for those patients with or without shocks delivered in the field. Logistic regression analysis assessed the association of shock delivery with pre-hospital return of spontaneous circulation (ROSC), survival to hospital discharge and favorable neurological outcome as well. RESULTS: Of the 9902 included cases, 3415 (34.5%) were initially in PEA and 6487 (65.5%) were in asystole. 744 (21.8%) PEA and 1134 (17.5%) asystolic patients underwent rhythm conversions and received subsequent shocks. For asystolic patients, the adjusted odds ratios (ORs) of shock delivery for pre-hospital ROSC, survival to discharge and favorable neurological outcome were 1.862 (95%CI 1.590-2.180), 3.778 (95%CI 2.374-6.014) and 4.154 (95%CI 2.192-7.871) respectively, while for PEA patients they were 0.951 (95%CI 0.796-1.137), 1.115 (95%CI 0.720-1.726) and 1.373 (95%CI 0.790-2.385) respectively. CONCLUSIONS: Conversion to shockable rhythms was associated with better outcomes in initially asystolic OHCA patients, whereas such associations were not observed in patients initially in PEA.


Assuntos
Reanimação Cardiopulmonar , Cardioversão Elétrica , Parada Cardíaca/fisiopatologia , Frequência Cardíaca/fisiologia , Parada Cardíaca Extra-Hospitalar/terapia , Adulto , Idoso , Reanimação Cardiopulmonar/efeitos adversos , Reanimação Cardiopulmonar/instrumentação , Reanimação Cardiopulmonar/métodos , China , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/métodos , Cardioversão Elétrica/estatística & dados numéricos , Fenômenos Eletrofisiológicos , Serviços Médicos de Emergência/métodos , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologia , Parada Cardíaca Extra-Hospitalar/mortalidade , Análise de Sobrevida
10.
J Am Heart Assoc ; 5(5)2016 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-27207999

RESUMO

BACKGROUND: The safety and long-term outcome of systemic thrombolysis in patients receiving antiplatelet medications remain subjects of great clinical significance. The objective of this meta-analysis was to determine how prestroke antiplatelet therapy affects the risks and benefits of intravenous thrombolysis in patients with acute ischemic stroke. METHODS AND RESULTS: A dual-reviewer search was conducted in PubMed and EMBASE databases through November 2015, from which 19 studies involving a total of 108 588 patients with acute ischemic stroke were identified based on preset inclusion criteria. Information on study designs, patient characteristics, exposures, outcomes, and adjusting confounders was extracted, and estimates were combined by using random-effects models. The pooled crude estimates suggested that taking long-term antiplatelet medications was associated with higher odds of symptomatic intracranial hemorrhage (odds ratio [OR] 1.70, 95% CI 1.47-1.97) and death (OR 1.46, 95% CI 1.22-1.75) and lower odds of favorable functional outcomes (OR 0.86, 95% CI 0.80-0.93). However, the combined confounder-adjusted results only confirmed a relatively weak positive association between prior antiplatelet therapy and symptomatic intracranial hemorrhage (OR 1.21, 95% CI 1.02-1.44) and demonstrated no significant relationship between antiplatelet therapy and the other 2 outcomes (favorable outcome OR 1.09, 95% CI 0.96-1.24; death OR 1.02, 95% CI 0.98-1.07). Subgroup analyses revealed that the associations between prestroke antiplatelet therapy and outcomes were dependent on time and antiplatelet agents. CONCLUSIONS: Patients with acute ischemic stroke receiving long-term antiplatelet medications were associated with greater risks of developing symptomatic intracranial hemorrhage after systemic thrombolysis. However, the overall independent association between prestroke antiplatelet therapy and unfavorable outcomes or mortality was insignificant.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/epidemiologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Isquemia Encefálica/complicações , Humanos , Hemorragias Intracranianas/induzido quimicamente , Razão de Chances , Fatores de Risco , Acidente Vascular Cerebral/etiologia
11.
Chem Commun (Camb) ; 51(7): 1297-300, 2015 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-25478680

RESUMO

Selective meta-arylation of O-ß-naphthyl carbamate has been accomplished using Pd(OAc)2 as a catalyst precursor and K2S2O8 with AgOAc as the oxidant. A range of aryl boronic acids could be introduced in moderate to good yields. Mechanistic investigation shows that the carbamate substituent has a unique effect and the reaction undergoes an ortho-carbometallation/meta-direct arylation process.

12.
J Cancer Res Clin Oncol ; 141(5): 909-21, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25373315

RESUMO

PURPOSE: Vascular endothelial growth factor signaling pathway plays a crucial role in angiogenesis and has become a promising target for cancer drug development. We aimed to quantify the overall efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer (NSCLC). METHODS: Electronic databases were searched for randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for NSCLC patients. The extracted data on objective response rates (ORRs), disease control rates (DCRs), progression-free survival (PFS) and overall survival (OS) were pooled. Common adverse events (AEs) were also studied. RESULTS: A total of 33 RCTs involving 17,396 patients were included. Compared with non-angiogenesis inhibitors, angiogenesis inhibitors resulted in significant improvement in PFS (HR, 0.81; 95 % CI 0.76-0.85; p < 0.001), OS (HR, 0.95; 95 % CI 0.92-0.98; p = 0.004), ORR (RR, 1.54; 95 % CI 1.37-1.73; p < 0.001) and DCR (RR, 1.18; 95 % CI 1.10-1.27; p < 0.001). The AEs associated with angiogenesis inhibitors were generally predictable and manageable. CONCLUSION: Angiogenesis inhibitors were superior to non-angiogenesis inhibitors in terms of ORR, DCR, PFS and OS in advanced NSCLC patients. Further studies are warranted to explore the predictive biomarkers to pick up those who may gain utmost benefit from anti-angiogenic therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Hemorragia/induzido quimicamente , Humanos , Indóis/uso terapêutico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Razão de Chances , Compostos de Fenilureia/uso terapêutico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Quinazolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sorafenibe , Sulfonamidas/uso terapêutico , Sunitinibe , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
13.
Vaccine ; 24(11): 1941-8, 2006 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-16307833

RESUMO

The induction of opsonic antibodies directed against capsular polysaccharides (Ps) is an important mechanism by which immunization protects against the development of invasive pneumococcal (Pn) infection. In preparing Pn vaccines, it is necessary to compare different manufacturing lots of capsular Ps, or to compare oligosaccharides used for conjugate vaccines with native capsular Ps, in order to insure that important epitopes of the Ps are maintained. We have developed an opsonic-antibody inhibition assay (OIA) to compare the functional epitopes of different capsular Ps preparations in vitro. Components of the OIA are primary neutrophils, rabbit complement (C'), and type-specific antibody (Ab). After conditions for optimal opsonic killing were determined for each Pn serotype, anti-Pn Ab was pre-incubated with different dilutions of purified capsular Ps, then added to the OIA mix. Plotting the % bacteria killed versus Ps concentration (log transformed) yielded a linear curve that was used to quantify the concentration of capsular Ps which inhibited the bacteria killing by 50% (IC50). The IC50 was determined for 8 Pn Ps types. These ranged between 6 ng/ml for type 6B and 1268 ng/ml for type 23F. Importantly OIA curves were statistically identical for two different manufacturing lots of capsular Ps for the 8 Pn Ps types. We conclude that differences among capsular Ps used for Pn vaccines could be detected with an OIA assay and these differences may predict the ability of Ps preparations to induce functionally active antibody when formulated into vaccines.


Assuntos
Cápsulas Bacterianas/imunologia , Epitopos/análise , Técnicas Imunológicas , Proteínas Opsonizantes/imunologia , Streptococcus pneumoniae/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/análise , Antígenos de Bactérias/imunologia , Cápsulas Bacterianas/análise , Contagem de Colônia Microbiana , Proteínas do Sistema Complemento , Epitopos/imunologia , Feminino , Humanos , Concentração Inibidora 50 , Macaca mulatta , Masculino , Neutrófilos/imunologia , Fagocitose
14.
Clin Gastroenterol Hepatol ; 3(5): 499-506, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15880320

RESUMO

BACKGROUND & AIMS: Black American patients are less likely to eradicate hepatitis C virus (HCV) infections during treatment with peginterferon (PEG-IFN) and ribavirin. We hypothesized that racial differences in IFN-stimulated antiviral gene induction during treatment might be responsible. METHODS: We examined myxovirus resistance-A (MxA), RNA-dependent protein kinase (PKR), 2'-5' oligoadenylate synthetase (2,5-OAS), and adenosine deaminase-1 (ADAR1) gene expression in the peripheral blood mononuclear cells (PBMCs) of 31 black and 11 white HCV genotype 1 patients at baseline and at weeks 4-12 during PEG-IFN alfa-2a combination treatment. The primary study end point was the early virologic response (EVR)-either an undetectable serum HCV-RNA level or a > or =2-log decrease in serum HCV-RNA level at week 12 compared with week 0. RESULTS: The EVR rate was 67.7% in blacks and 63.6% in whites. Both blacks and whites experienced a significant (200%-500%) increase in 2,5-OAS, MxA, PKR, and ADAR1 expression at treatment weeks 4-12 compared with baseline (P < .01). However, the relationship between IFN-stimulated gene expression and the EVR differed by race. White responders exhibited higher 2,5-OAS and MxA levels at week 4 than white nonresponders (P < .05). IFN-stimulated gene levels did not correlate with EVR in blacks. Black responders had much lower MxA and PKR levels at week 4 than black nonresponders (P < .05). However, black responders maintained increased 2,5-OAS, MxA, and PKR levels from weeks 4-12, whereas the levels decreased to baseline at weeks 8-12 in black nonresponders. CONCLUSIONS: The mechanisms of resistance to PEG-IFN combination therapy may be different in black and white HCV genotype 1 patients.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Antivirais/uso terapêutico , Grupo com Ancestrais do Continente Europeu/genética , Hepatite C Crônica/genética , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , 2',5'-Oligoadenilato Sintetase/sangue , 2',5'-Oligoadenilato Sintetase/genética , Adenosina Desaminase/sangue , Adenosina Desaminase/genética , Adulto , Quimioterapia Combinada , Feminino , Proteínas de Ligação ao GTP/sangue , Proteínas de Ligação ao GTP/genética , Expressão Gênica , Genótipo , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas de Resistência a Myxovirus , Estudos Prospectivos , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/uso terapêutico , eIF-2 Quinase/sangue , eIF-2 Quinase/genética
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