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1.
Br J Surg ; 105(5): 535-543, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29465744

RESUMO

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Ductal de Mama/tratamento farmacológico , Tratamento Conservador/métodos , Estadiamento de Neoplasias , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia
2.
Leukemia ; 31(11): 2347-2354, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28322237

RESUMO

Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.


Assuntos
Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Óxidos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio , Feminino , Humanos , Leucemia Promielocítica Aguda/etiologia , Leucemia Promielocítica Aguda/genética , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/genética , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
3.
Prostate Cancer Prostatic Dis ; 20(3): 300-304, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28349981

RESUMO

BACKGROUND: Physician practices that offer ancillary medical services may refer their patients for such services, a process known as self-referral. We wanted to evaluate how utilization and cost of care differ for men diagnosed with prostate cancer in a self-referral practice (SRP) compared to a traditional urologic practice. METHODS: A total of 17 982 men aged 66 years and older diagnosed with localized prostate cancer from 2006 to 2009 were identified from the Texas Cancer Registry. A total of 13 SRPs in the state of Texas were evaluated. We used multilevel logistic regression models that evaluated the odds of receiving a specific type of treatment. RESULTS: Men diagnosed in SRPs were more likely to receive upfront treatment (vs watchful waiting/active surveillance) than men diagnosed by traditional practices (92.7% vs 89%; adjusted odds ratio (AOR) 1.61, 95% confidence interval (CI) 1.30-2.00; P<0.001) and were more likely to be treated with external beam radiation (47.4% vs 34.1%; AOR 1.59, 95% CI 1.37-1.84; P<0.001). This persisted for both favorable and unfavorable risk cancer. Median annual prostate cancer care cost was $2460 (95% CI $1663-$3368) higher for men diagnosed by SRPs. Limitations include data limited to men aged 65 years or older and geographic concentration of SRPs in Texas may not depict nationwide patterns. CONCLUSIONS: Older men diagnosed with prostate cancer in SRPs are more likely to undergo upfront treatment and to receive radiation treatment. This may increase appropriate treatment of unfavorable disease but contribute to overtreatment of favorable disease.


Assuntos
Neoplasias da Próstata/radioterapia , Radioterapia/instrumentação , Idoso , Idoso de 80 Anos ou mais , Custos de Cuidados de Saúde , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Radioterapia/economia , Resultado do Tratamento , Urologistas
5.
Cell Death Differ ; 22(12): 2133-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26045051

RESUMO

MLN4924 (pevonedistat), an inhibitor of the Nedd8 activating enzyme (NAE), has exhibited promising clinical activity in acute myelogenous leukemia (AML). Here we demonstrate that MLN4924 induces apoptosis in AML cell lines and clinical samples via a mechanism distinct from those observed in other malignancies. Inactivation of E3 cullin ring ligases (CRLs) through NAE inhibition causes accumulation of the CRL substrate c-Myc, which transactivates the PMAIP1 gene encoding Noxa, leading to increased Noxa protein, Bax and Bak activation, and subsequent apoptotic changes. Importantly, c-Myc knockdown diminishes Noxa induction; and Noxa siRNA diminishes MLN4924-induced killing. Because Noxa also neutralizes Mcl-1, an anti-apoptotic Bcl-2 paralog often upregulated in resistant AML, further experiments have examined the effect of combining MLN4924 with BH3 mimetics that target other anti-apoptotic proteins. In combination with ABT-199 or ABT-263 (navitoclax), MLN4924 exerts a synergistic cytotoxic effect. Collectively, these results provide new insight into MLN4924-induced engagement of the apoptotic machinery that could help guide further exploration of MLN4924 for AML.


Assuntos
Apoptose/efeitos dos fármacos , Ciclopentanos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Pirimidinas/farmacologia , Regulação para Cima/efeitos dos fármacos , Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Sulfonamidas/farmacologia
6.
Oncogene ; 34(2): 144-53, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-24362531

RESUMO

The signaling mediated by c-MET and its ligand, hepatocyte growth factor (HGF), has been implicated in malignant progression of cancer involving stimulation of proliferation, invasion and metastasis. We studied the c-MET/HGF axis as a mediator of tumor-stromal interaction in ovarian cancer and the value of targeting c-MET for the treatment of ovarian cancer. To assess c-MET signaling, we established in vitro models of the microenvironment using primary and immortalized human fibroblasts from normal ovary and tumor samples and epithelial ovarian cancer cell lines. We found that fibroblast from normal ovaries secreted high levels of HGF (1500-3800 pg/ml) as compared with tumor-derived fibroblasts (undetectable level) and could elicit cellular biological responses on c-MET-expressing ovarian cancer cells including increase of cell proliferation and migration (2- to 140-fold increase). HGF secreted by fibroblasts was also found sequestered within extracellular matrices (ECMs) and when degraded this ECM-derived HGF stimulated cancer cell migration (1.5- to 24-fold). In cells containing constitutive c-MET phosphorylation, recombinant HGF and fibroblast-derived HGF negligibly affect c-MET phosphorylation on Tyr(1234) and Tyr(1003). However, both sources of HGF increased the phosphorylation of c-MET on Tyr(1349), the multi-substrate docking site, by more than sixfold and led to activation of downstream signaling transducers. DCC-2701 (Deciphera Pharmaceuticals, LLC), a novel c-MET/TIE-2/VEGFR inhibitor was able to effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with a HGF antagonist in vitro. Importantly, DCC-2701's anti-proliferative activity was dependent on c-MET activation induced by stromal human fibroblasts and to a lesser extent exogenous HGF. Our data suggest for the first time that DCC-2701 may be superior to HGF antagonists that are in clinical trials and that pTyr(1349) levels might be a good indicator of c-MET activation and likely response to targeted therapy as a result of signals from the microenvironment.


Assuntos
Aminopiridinas/farmacologia , Anilidas/farmacologia , Fator de Crescimento de Hepatócito/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Animais , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Progressão da Doença , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Sci Total Environ ; 506-507: 109-17, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25460945

RESUMO

The relationship between the subcellular distribution of accumulated toxic metals into five operational fractions (subsequently combined into presumed detoxified and non-detoxified components) and toxicity in the clam Scrobicularia plana was investigated under different laboratory exposures. Clams were exposed to metal contaminated media (water and diet) and analysed for the partitioning of accumulated As, Cu and Zn into subcellular fractions. In general, metallothionein-like proteins, metal-rich granules and cellular debris in different proportions acted as main storage sites of accumulated metals in the clam soft tissues for these three metals. No significant differences were noted in the accumulation rates of As, Cu and Zn of groups of individuals with or without apparent signs of toxicity after up to 30 days of exposure to naturally contaminated sediment mixtures. There was, however, an increased proportional accumulation of Cu in the non-detoxified fraction with increased Cu accumulation rate in the clams, suggesting that the Cu uptake rate from contaminated sediments exceeded the combined rates of elimination and detoxification of Cu, with the subsequent likelihood for toxic effects in the clams.


Assuntos
Bivalves/metabolismo , Sedimentos Geológicos/química , Metais/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Monitoramento Ambiental , Metalotioneína/metabolismo , Metais/análise , Metais/toxicidade , Distribuição Tecidual , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
8.
Am J Transplant ; 15(1): 234-41, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25534448

RESUMO

The clonal expansion of effector T cells and subsequent generation of memory T cells are critical in determining the outcome of transplantation. While cytotoxic T lymphocytes induce direct cytolysis of target cells through secretion of Granzyme-B (GrB), they also express cytoplasmic serine protease inhibitor-6 (Spi6) to protect themselves from GrB that has leaked from granules. Here, we studied the role of GrB/Spi6 axis in determining clonal expansion of alloreactive CD8-T cells and subsequent generation of memory CD8-T cells in transplantation. CD8-T cells from Spi6(-/-) mice underwent more GrB mediated apoptosis upon alloantigen stimulation in vitro and in vivo following adoptive transfer into an allogeneic host. Interestingly, while OT1.Spi6(-/-) CD8 T cells showed significantly lower clonal expansion following skin transplants from OVA mice, there was no difference in the size of the effector memory CD8-T cells long after transplantation. Furthermore, lack of Spi6 resulted in a decrease of short-lived-effector-CD8-cells but did not impact the pool of memory-precursor-effector-CD8-cells. Similar results were found in heart transplant models. Our findings suggest that the final alloreactive CD8-memory-pool-size is independent from the initial clonal-proliferation as memory precursors express low levels of GrB and therefore are independent of Spi6 for survival. These data advance our understanding of memory T cells generation in transplantation and provide basis for Spi6 based strategies to target effector T cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Doença Enxerto-Hospedeiro/imunologia , Transplante de Coração , Memória Imunológica/imunologia , Proteínas de Membrana/fisiologia , Serpinas/fisiologia , Transplante de Pele , Linfócitos T Citotóxicos/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , Sobrevivência Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Doença Enxerto-Hospedeiro/patologia , Granzimas/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Linfócitos T Citotóxicos/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
9.
Mar Environ Res ; 101: 215-224, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25088525

RESUMO

The fouling barnacle Amphibalanus amphitrite is a cosmopolitan biomonitor of trace metal bioavailabilities, with an international comparative data set of body metal concentrations. Bioavailabilities of As, Cd, Cr, Cu, Fe, Mn, Pb, V and Zn to A. amphitrite were investigated at 19 sites along the Iranian coast of the understudied Persian Gulf. Commercial and fishing ports showed extremely high Cu bioavailabilities, associated with high Zn bioavailabilities, possibly from antifouling paints and procedures. V availability was raised at one port, perhaps associated with fuel leakage. Cd bioavailabilities were raised at sites near the Strait of Hormuz, perhaps affected by adjacent upwelling off Oman. The As data allow a reinterpretation of the typical range of accumulated As concentrations in A. amphitrite. The Persian Gulf data add a new region to the A. amphitrite database, confirming its importance in assessing the ecotoxicologically significant trace metal contamination of coastal waters across the world.


Assuntos
Monitoramento Ambiental , Metais/metabolismo , Thoracica/metabolismo , Animais , Disponibilidade Biológica , Irã (Geográfico) , Análise de Componente Principal
11.
Aquat Toxicol ; 154: 121-30, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24880784

RESUMO

Biodynamic modelling was used to investigate the uptake and accumulation of three trace metals (Ag, As, Zn) by the deposit feeding estuarine bivalve mollusc Scrobicularia plana. Radioactive labelling techniques were used to quantify the rates of trace metal uptake (and subsequent elimination) from water and sediment diet. The uptake rate constant from solution (±SE) was greatest for Ag (3.954±0.375 l g(-1) d(-1)) followed by As (0.807±0.129 l g(-1) d(-1)) and Zn (0.103±0.016 l g(-1) d(-1)). Assimilation efficiencies from ingested sediment were 40.2±1.3% (Ag), 31.7±1.0% (Zn) and 25.3±0.9% (As). Efflux rate constants after exposure to metals in the solution or sediment fell in the range of 0.014-0.060 d(-1). By incorporating these physiological parameters into biodynamic models, our results showed that dissolved metal is the predominant source of accumulated Ag, As and Zn in S. plana, accounting for 66-99%, 50-97% and 52-98% of total accumulation of Ag, As and Zn, respectively, under different field exposure conditions. In general, model-predicted steady state concentrations of Ag, As and Zn matched well with those observed in clams collected in SW England estuaries. Our findings highlight the potential of biodynamic modelling to predict Ag, As and Zn accumulation in S. plana, taking into account specific dissolved and sediment concentrations of the metals at a particular field site, together with local water and sediment geochemistries.


Assuntos
Bivalves/metabolismo , Metais/metabolismo , Modelos Biológicos , Poluentes Químicos da Água/metabolismo , Animais , Inglaterra , Sedimentos Geológicos/química , Metais/análise , Oligoelementos/análise , Oligoelementos/metabolismo , Poluentes Químicos da Água/análise
12.
Leukemia ; 28(9): 1774-83, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24699305

RESUMO

The development of effective treatment strategies for most forms of acute myeloid leukemia (AML) has languished for the past several decades. There are a number of reasons for this, but key among them is the considerable heterogeneity of this disease and the paucity of molecular markers that can be used to predict clinical outcomes and responsiveness to different therapies. The recent large-scale sequencing of AML genomes is now providing opportunities for patient stratification and personalized approaches to treatment that are based on individual mutational profiles. It is particularly notable that studies by The Cancer Genome Atlas and others have determined that 44% of patients with AML exhibit mutations in genes that regulate methylation of genomic DNA. In particular, frequent mutation has been observed in the genes encoding DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2), as well as Tet oncogene family member 2. This review will summarize the incidence of these mutations, their impact on biochemical functions including epigenetic modification of genomic DNA and their potential usefulness as prognostic indicators. Importantly, the presence of DNMT3A, IDH1 or IDH2 mutations may confer sensitivity to novel therapeutic approaches, including the use of demethylating agents. Therefore, the clinical experience with decitabine and azacitidine in the treatment of patients harboring these mutations will be reviewed. Overall, we propose that understanding the role of these mutations in AML biology will lead to more rational therapeutic approaches targeting molecularly defined subtypes of the disease.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/genética , Mutação , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Transtornos Mieloproliferativos/genética , Proteínas Nucleares/genética , Prognóstico , Tirosina Quinase 3 Semelhante a fms/genética
14.
Blood Cancer J ; 3: e145, 2013 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-24013666

RESUMO

The ability to target myeloid leukemia with immunotherapy would represent a significant therapeutic advance. We report here immunological analysis of clinical trials of primary and secondary vaccination with K562/GM-CSF immunotherapy in adult chronic phase chronic myeloid leukemia patients (CML-CP) with suboptimal responses to imatinib mesylate. Using serological analysis of recombinant cDNA expression libraries of K562 with autologous vaccinated patient serum, we have identified 12 novel chronic myeloid leukemia-associated antigens (LAAs). We show that clinical responses following K562/GM-CSF vaccination are associated with induction of high-titer antibody responses to multiple LAAs. We observe markedly discordant patterns of baseline and induced antibody responses in these identically vaccinated patients. No single antigen was recognized in all responses to vaccination. We demonstrate that an additional 'booster' vaccination series can be given safely to those with inadequate responses to initial vaccination, and is associated with more frequent induction of IgG responses to antigens overexpressed in K562 vaccine compared with primary CML-CP. Finally, those with induced immune responses to the same LAAs often shared HLA subtypes and patients with clinical responses following vaccination recognized a partially shared but non-identical spectrum of antigens; both findings have potentially significant implications for cancer vaccine immunotherapy.

15.
AIDS Res Treat ; 2013: 528904, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24455220

RESUMO

Background. The Centers for Disease Control and Prevention (CDC) recommends testing and linkage to care for persons most likely infected with hepatitis C virus (HCV), including persons with human immunodeficiency virus. We explored facilitators and barriers to integrating HCV point-of-care (POC) testing into standard operations at an urban STD clinic. Methods. The OraQuick HCV rapid antibody test was integrated at the Denver Metro Health Clinic (DMHC). All clients with at least one risk factor were offered the POC test. Research staff conducted interviews with clients (three HCV positive and nine HCV negative). Focus groups were conducted with triage staff, providers, and linkage-to-care counselors. Results. Clients were pleased with the ease of use and rapid return of results from the HCV POC test. Integrating the test into this setting required more time but was not overly burdensome. While counseling messages were clear to staff, clients retained little knowledge of hepatitis C infection or factors related to risk. Barriers to integrating the HCV POC test into clinic operations were loss to follow-up and access to care. Conclusion. DMHC successfully integrated HCV POC testing and piloted a HCV linkage-to-care program. Providing testing opportunities at STD clinics could increase identification of persons with HCV infection.

16.
J Clin Virol ; 54(3): 213-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22560051

RESUMO

BACKGROUND: Approximately 4.1 million Americans are estimated to have been infected with hepatitis C virus (HCV), 45-85% of whom are unaware of their infection. Persons who inject drugs (PWID) account for 55.8% of all persons with HCV antibody (anti-HCV) in the U.S. PWID have limited access to healthcare and are infrequently tested for anti-HCV using conventional laboratory assays. OBJECTIVE: To evaluate performance characteristics (sensitivity and specificity) of three, pre-market rapid point-of-care tests (one oral fluid and two finger-stick assays) from two manufacturers (Chembio and MedMira) in settings providing services to young adult PWID in San Diego, CA. STUDY DESIGN: Behavioral risk assessment surveys and testing for HCV were conducted among persons who reported injection drug use (IDU) within the past 6 months as part of the Study to Assess Hepatitis C Risk (STAHR) among PWID aged 18-40 years in 2009-2010. Sensitivity and specificity of the rapid anti-HCV assays were evaluated among STAHR participants, using two commonly used testing algorithms. RESULTS: Variability in sensitivity (76.6-97.1%) and specificity (99.0-100.0%) was found across assays. The highest sensitivity achieved for the Chembio finger-stick blood, Chembio oral fluid and MedMira finger-stick blood tests was 97.1%, 85.4% and 80.0% respectively; the highest specificity was 99.0%, 100.0% and 100.0%, respectively. In multivariate analysis false negative anti-HCV results were associated with female sex for the MedMira blood assay. CONCLUSIONS: Sensitive anti-HCV rapid assays are appropriate and feasible for high-prevalence, high-risk populations such as young PWID.


Assuntos
Técnicas de Laboratório Clínico/métodos , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , Virologia/métodos , Adolescente , Adulto , Feminino , Humanos , Imunoensaio/métodos , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Abuso de Substâncias por Via Intravenosa/complicações , Fatores de Tempo , Estados Unidos , Adulto Jovem
17.
Ecotoxicology ; 21(2): 576-90, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22083342

RESUMO

The accumulation, subcellular distribution and speciation of arsenic in the polychaete Arenicola marina were investigated under different laboratory exposure conditions representing a range of metal bioavailabilities, to gain an insight into the physiological mechanisms of how A. marina handles bioaccumulated arsenic and to improve our understanding of the potential ecotoxicological significance of bioaccumulated arsenic in this deposit-feeder. The exposure conditions included exposure to sublethal concentrations of dissolved arsenate, exposure to sublethal concentrations of sediment-bound metal mining mixtures, and exposure to lethal concentrations of sediment-bound metal mining mixtures and arsenic- and multiple metal-spiked sediments. The sub-lethal exposures indicate that arsenic bioaccumulated by the deposit-feeding polychaete A. marina is stored in the cytosol as heat stable proteins (~50%) including metallothioneins, possibly as As (III)-thiol complexes. The remaining arsenic is mainly accumulated in the fraction containing cellular debris (~20%), with decreasing proportions accumulated in the metal-rich granules, organelles and heat-sensitive proteins fractions. A biological detoxified metal compartment including heat stable proteins and the fraction containing metal-rich granules is capable of binding arsenic coming into the cells at a constant rate under sublethal arsenic bioavailabilities. The remaining arsenic entering the cell is bound loosely into the cellular debris fraction, which can be subsequently released and diverted to an expanding detoxified pool. Our results suggest that a metal sensitive compartment comprising the cellular debris, enzymes and organelles fractions may be more representative of the toxic effects observed.


Assuntos
Arsenicais/efeitos adversos , Arsenicais/farmacocinética , Inativação Metabólica/fisiologia , Poliquetos/efeitos dos fármacos , Poluentes Químicos da Água/farmacocinética , Poluentes Químicos da Água/toxicidade , Animais , Arsenicais/análise , Disponibilidade Biológica , Fracionamento Celular , Citosol/efeitos dos fármacos , Citosol/metabolismo , Sedimentos Geológicos/química , Poliquetos/fisiologia , Poluentes Químicos da Água/análise
18.
AIDS Care ; 23 Suppl 1: 45-53, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21660750

RESUMO

As the HIV/AIDS epidemic and the spread of sexually transmitted infections (STIs) in China has come to the forefront of public health attention, female sex workers (FSWs) and their clients (CFSWs) are becoming increasingly important to HIV/STI prevention efforts. This secondary analysis uses data abstracted from the Chinese Health and Family Life Survey 1999-2000 to report prevalence rates of two STIs as well as sexual risk behaviors for CFSWs - men who paid for sex with FSWs in the past 12 months - in comparison with men who had not patronized FSWs. Among 1879 Chinese CFSWs who completed anonymous interviews and urine testing, 152 (6.3%, weighted) said they had paid for sex in the past 12 months and 18.8% of CFSWs (weighted) tested positive for gonorrhea. CFSWs were 10 times more likely to have an STI (either self-reported or tested) than non-client Chinese men, and they were equally likely to use condoms inconsistently with their spouses. This study highlights the importance of studying CFSWs who use condoms inconsistently and do not practice safe sex with their spouse as a potential bridge population. Prevention and intervention efforts should target this bridge population and include education on HIV/AIDS and STI transmission, condom promotion, marriage counseling, destigmatization of HIV and STIs, and promotion of STI diagnosis and treatment.


Assuntos
Preservativos/estatística & dados numéricos , Trabalho Sexual/estatística & dados numéricos , Parceiros Sexuais , Doenças Sexualmente Transmissíveis/epidemiologia , China/epidemiologia , Feminino , Gonorreia/epidemiologia , Gonorreia/transmissão , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Prevalência , Fatores de Risco , Assunção de Riscos , Sexo Seguro , Doenças Sexualmente Transmissíveis/prevenção & controle , Doenças Sexualmente Transmissíveis/transmissão , Fatores Socioeconômicos
19.
Sci Total Environ ; 409(8): 1589-602, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21315427

RESUMO

Many estuaries of southwest England were heavily contaminated with toxic metals associated with the mining of copper and other metals, particularly between 1850 and 1900. The question remains whether the passage of time has brought remediation to these estuaries. In 2003 and 2006 we revisited sites in 5 metal-contaminated estuaries sampled in the 1970s and 1980s - Restronguet Creek, Gannel, West Looe, East Looe and Tavy. We evaluate changes in metal contamination in sediments and in metal bioavailabilities in sediments and water to local organisms employed as biomonitors. We find that the decline in contamination in these estuaries is complex. Differences in bioavailable contamination in the water column were detectable, as were significant detectable changes in at least some estuaries in bioavailable metal contamination originating from sediments. However, in the 100 years since mining activities declined, bioavailable contamination has not declined to the regional baseline in any estuary affected by the mine wastes. The greatest decline in contamination occurred in the one instance (East Looe) where a previous industrial source of (Ag) contamination was considered. We used the macroalgae Fucus vesiculosus and Ascophyllum nodosum as biomonitors of dissolved metal bioavailabilities and the deposit feeders Nereis diversicolor and Scrobicularia plana as biomonitors of bioavailable metal in sediments. We found no systematic decrease in the atypically high Ag, Cu, Pb and Zn concentrations in the estuarine sediments over a 26 year period. Accumulated metal (Ag, As, Cu, Pb, and Zn) concentrations in the deposit feeders are similarly still atypically high in at least one estuary for each metal, and there is no consistent evidence for general decreases in sediment metal bioavailabilities over time. We conclude that the legacy of mining in sheltered estuaries of southwest England is the ongoing presence of sediments rich in metals bioavailable to deposit feeders, while dissolved metal bioavailabilities from this historical source alone are no longer atypically high.


Assuntos
Monitoramento Ambiental , Metais/análise , Poluentes Químicos da Água/análise , Animais , Arsênico/química , Bivalves/metabolismo , Inglaterra , Sedimentos Geológicos/química , Metais/metabolismo , Mineração , Poliquetos/metabolismo , Água do Mar/química , Alga Marinha/química , Alga Marinha/metabolismo , Poluentes Químicos da Água/metabolismo
20.
J Viral Hepat ; 18(7): 474-81, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20497311

RESUMO

Approximately 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S.; most are not aware of their infection. Our objectives were to examine HCV testing practices to determine which patient characteristics are associated with HCV testing and positivity, and to estimate the prevalence of HCV infection in a high-risk urban population. The study subjects were all patients included in the baseline phase of the Hepatitis C Assessment and Testing Project (HepCAT), a serial cross-sectional study of HCV screening strategies. We examined all patients with a clinic visit to Montefiore Medical Center from 1/1/08 to 2/29/08. Demographic information, laboratory data and ICD-9 diagnostic codes from 3/1/97-2/29/08 were extracted from the electronic medical record. Risk factors for HCV were defined based on birth date, ICD-9 codes and laboratory data. The prevalence of HCV infection was estimated assuming that untested subjects would test positive at the same rate as tested subjects, based on risk-factors. Of 9579 subjects examined, 3803 (39.7%) had been tested for HCV and 438 (11.5%) were positive. The overall prevalence of HCV infection was estimated to be 7.7%. Risk factors associated with being tested and anti-HCV positivity included: born in the high-prevalence birth-cohort (1945-64), substance abuse, HIV infection, alcohol abuse, diagnosis of cirrhosis, end-stage renal disease, and alanine transaminase elevation. In a high-risk urban population, a significant proportion of patients were tested for HCV and the prevalence of HCV infection was high. Physicians appear to use a risk-based screening strategy to identify HCV infection.


Assuntos
Instituições de Assistência Ambulatorial , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Grupos Étnicos , Feminino , Hepacivirus/imunologia , Humanos , Laboratórios Hospitalares , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Saúde da População Urbana
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