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1.
Clin Exp Immunol ; 191(2): 180-188, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28960271

RESUMO

Innate lymphocyte populations, such as innate lymphoid cells (ILCs), γδ T cells, invariant natural killer T (iNK T) cells and mucosal-associated invariant T (MAIT) cells are emerging as important effectors of innate immunity and are involved in various inflammatory and autoimmune diseases. The aim of this study was to assess the frequencies and absolute numbers of innate lymphocytes as well as conventional lymphocytes and monocytes in peripheral blood from a cohort of anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV) patients. Thirty-eight AAV patients and 24 healthy and disease controls were included in the study. Patients with AAV were sampled both with and without immunosuppressive treatment, and in the setting of both active disease and remission. The frequencies of MAIT and ILC2 cells were significantly lower in patients with AAV and in the disease control group compared to healthy controls. These reductions in the AAV patients remained during remission. B cell count and frequencies were significantly lower in AAV in remission compared to patients with active disease and disease controls. Despite the strong T helper type 2 (Th) preponderance of eosinophilic granulomatosis with polyangiitis, we did not observe increased ILC2 frequency in this cohort of patients. The frequencies of other cell types were similar in all groups studied. Reductions in circulating ILC2 and MAIT cells reported previously in patients with AAV are not specific for AAV, but are more likely to be due to non-specific manifestations of renal impairment and chronic illness. Reduction in B cell numbers in AAV patients experiencing remission is probably therapy-related.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Linfócitos B/imunologia , Rim/patologia , Subpopulações de Linfócitos/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Células T Matadoras Naturais/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Imunidade Inata , Terapia de Imunossupressão , Contagem de Linfócitos , Masculino , Microcirculação , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo
2.
Sci Total Environ ; 573: 799-809, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27592467

RESUMO

Chronic oil pollution poses substantial risks to marine birds and other marine wildlife worldwide. On Canada's Pacific coast, the negative ecological consequences to marine birds and marine ecosystems in general remain poorly understood. Using information relating to oil spill probability of occurrence, areas of overall importance to marine birds, and the at-sea distribution and density of 12 marine bird species and seven bird groups, including multiple Species at Risk, we undertook a spatial assessment of risk. Our results identify two main areas important to marine birds potentially at higher risk of exposure to oil. For individual bird species or species groups, those predicted to have elevated bird densities near the mainland and the northeast coast of Vancouver Island were identified as being at higher potential risk of exposure. Our results, however, should be considered preliminary. As with other anthropogenic stressors, in order to better understand and subsequently mitigate the consequences of chronic oil pollution on marine birds, improved information relating to marine birds and the occurrence of oil spills on Canada's Pacific coast is needed.


Assuntos
Aves/metabolismo , Exposição Ambiental/análise , Poluição por Petróleo/análise , Medição de Risco/métodos , Poluentes Químicos da Água/análise , Animais , Organismos Aquáticos , Colúmbia Britânica , Monitoramento Ambiental
3.
Mar Pollut Bull ; 69(1-2): 157-64, 2013 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-23453813

RESUMO

Illegal discharge of waste oil from ships is a major source of mortality for seabirds globally. Using linear and log-linear regression, we explored the relationship between detection rates of marine oily discharges and surveillance effort at different time scales, based on data collected in the Canadian Pacific Ocean by the National Aerial Surveillance Program (NASP) from 1997 to 2006. We introduce an approach for quantifying reductions in discharge rates with increased surveillance while controlling appropriately for surveillance effort, as standard linear correction for effort can introduce considerable bias. Despite low probabilities of detection (0.088-1.1%), we found evidence for reduced discharge rates with increasing surveillance effort for data summarized monthly and bimonthly in region A, which is closest to the NASP base airport. Using residuals derived from the best-fit log-linear models, we found detected discharge rates declined annually (-[0.070 spills/month]×year).


Assuntos
Aeronaves , Monitoramento Ambiental/métodos , Poluição por Petróleo/análise , Navios , Poluentes Químicos da Água/análise , Poluição Química da Água/estatística & dados numéricos , Canadá , Oceano Pacífico , Poluição por Petróleo/legislação & jurisprudência , Poluição por Petróleo/estatística & dados numéricos , Poluição Química da Água/legislação & jurisprudência
4.
Epidemiol Infect ; 141(10): 2140-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23217979

RESUMO

There are limited data examining whether outcomes of methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) are worse when caused by community-associated (CA) strains compared to HA strains. We reviewed all patients' charts at our institution from 1999 to 2009 that had MRSA first isolated only after 72 h of hospitalization (n=724). Of these, 384 patients had a MRSA-HAI according to CDC criteria. Treatment failure was similar in those infected with a phenotypically CA-MRSA strain compared to a phenotypically HA-MRSA strain (23% vs. 15%, P=0.10) as was 30-day mortality (16% vs. 19%, P=0.57). Independent risk factors associated with (P<0.05) treatment failure were higher Charlson Comorbidity Index, higher APACHE II score, and no anti-MRSA treatment. These factors were also associated with 30-day mortality, as were female gender, older age, MRSA bloodstream infection, MRSA pneumonia, and HIV. Our findings suggest that clinical and host factors, not MRSA strain type, predict treatment failure and death in hospitalized patients with MRSA-HAIs.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Feminino , Genótipo , Indicadores Básicos de Saúde , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento
5.
Rev Sci Tech ; 25(1): 119-23, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16796041

RESUMO

In 1997, a group of pastoral farmers, frustrated by governmental and official responses to their problems of rabbit control, introduced and spread the rabbit haemorrhagic disease virus in a clandestine operation that succeeded in distributing infection over a large area of the South Island before the disease was detected by government officials. The government concluded that eradication was not technically or economically feasible and the disease was accepted as being endemic. The episode highlighted the inadequate decision-making environment that existed at the time, now improved by the passage of the Hazardous Substances and New Organisms Act. It also highlights the importance of having a comprehensive biosecurity detection and response capability, including the ability to conduct prompt risk assessments, since preventing entry of biological agents may be difficult to achieve in the face of a determined adversary.


Assuntos
Infecções por Caliciviridae/veterinária , Contenção de Riscos Biológicos , Surtos de Doenças/veterinária , Vírus da Doença Hemorrágica de Coelhos , Coelhos/virologia , Animais , Animais Selvagens/virologia , Infecções por Caliciviridae/epidemiologia , Nova Zelândia/epidemiologia , Controle da População , Densidade Demográfica , Medição de Risco
6.
Biochem Soc Trans ; 30(Pt 6): 1056-9, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12440971

RESUMO

We have generated antisense plants of Brassica napus, targeting either the cytoplasmic Type I acetyl-CoA carboxylase or the beta-ketoacyl-acyl carrier protein reductase of the Type II dissociable fatty acid synthase, in order to investigate the importance of these components in regulating lipid metabolism in plants. Using a range of down-regulated plants, it has become clear that down-regulation of these genes also causes down-regulation of other components of lipid metabolism, at the activity, translational and transcriptional levels. These plants exhibit effects, not immediately predicted, on oil yield and carbon resource allocation in seeds.


Assuntos
Brassica napus/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica de Plantas , Oligonucleotídeos Antissenso/farmacologia , Ácidos Graxos/metabolismo , Homozigoto , Metabolismo dos Lipídeos , Modelos Biológicos , Modelos Químicos , Fenótipo
7.
J Vasc Surg ; 34(6): 1041-9, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11743558

RESUMO

PURPOSE: We documented the postoperative complication rate and the late results of simultaneous infrarenal aortic replacement and renal artery (RA) revascularization at the Cleveland Clinic and correlated these findings with the preoperative serum creatinine level (S(Cr)) and other baseline risk factors. METHODS: A retrospective review of hospital charts and outpatient records was supplemented with a telephone canvass and the invitation to return for a complimentary RA duplex scan, when a scan had not been done within the previous year. Data were collected for 73 consecutive patients (mean age, 69 years) who underwent aortic procedures that were combined with the repair of RA stenosis from 1989 to 1997 (mean follow-up, 44 months). The preoperative S(Cr) was 2 mg/dL or lower in 45 patients (group R1; median, 1.5 mg/dL) and was higher than 2 mg/dL in the remaining 28 patients (group R2; median, 2.6 mg/dL). RESULTS: Forty-seven of the patients in this series had aortic aneurysms, 15 patients had aortoiliac occlusive disease, and 11 patients had both types of lesions. Bilateral RA revascularization was necessary for seven patients in group R1 (15%) and for eight patients in group R2 (29%). Group R2 contained more patients with medically resistant hypertension (57%) than group R1 (29%, P = .019). Although there was no statistically significant difference between the 30-day mortality rates (group R1, 2.2%; group R2, 11%), the related in-hospital mortality rate for 15 bilateral RA revascularizations (13%) was nearly twice that of 58 unilateral revascularizations (6.9%). Patients in group R2 were at a higher risk for postoperative dialysis than those in group R1 (36% vs 6.7%, P = .008), and patients in group R2 had longer lengths of stay in the hospital (median, 14 days vs 9 days; P = .004). By means of Kaplan-Meier analysis, the 5-year survival rate was lower for patients in group R2 (53%; 95% CI, 33%-73%) than for patients in group R1 (85%; 95% CI, 74%-96%; log rank P = .005). Despite all other liabilities in group R2 patients, however, their resistant hypertension was cured or improved in 88% of cases and their S(Cr) appeared to decline with time. CONCLUSION: The early postoperative risk of simultaneous aortic/RA procedures appears to be highest in patients who have an elevated S(Cr), bilateral RA stenosis or occlusion, and a comparatively low long-term survival rate. In this particular group, the adjunctive use of endovascular techniques might conceivably reduce the magnitude of the planned surgical procedure and thus enhance the overall outcome.


Assuntos
Aneurisma Aórtico/complicações , Aneurisma Aórtico/cirurgia , Doenças da Aorta/complicações , Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular/métodos , Creatinina/sangue , Taxa de Filtração Glomerular , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/cirurgia , Idoso , Angiografia , Aneurisma Aórtico/mortalidade , Arteriopatias Oclusivas/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/mortalidade , Endarterectomia/efeitos adversos , Endarterectomia/instrumentação , Endarterectomia/métodos , Endarterectomia/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Modelos de Riscos Proporcionais , Obstrução da Artéria Renal/sangue , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Grau de Desobstrução Vascular
8.
Pharm Res ; 18(9): 1315-9, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11683246

RESUMO

PURPOSE: Targeted delivery of rifampicin loaded microspheres to the alveolar macrophage, the host cell for Mycobacterium tuberculosis (MTB), may be an effective targeted approach to pulmonary tuberculosis therapy. A guinea pig infection model has been adopted as a post-treatment screening method for antimicrobial effect. Insufflation and nebulization methods of drug delivery were evaluated. METHODS: Rifampicin alone (RIF, 1.03-1.72 mg/kg), within poly(lactide-co-glycolide) microspheres (R-PLGA, equivalent to 1.03-1.72 mg/kg) or polymer microparticles alone (PLGA) were administered by insufflation or nebulization, 24 h before bacterial aerosol exposure. Animals were infected with an aerosol containing a small number (2 x 10(5) cfu/mL) of virulent H37Rv strain of MTB. Lung and spleen tissue samples were collected 28 days after infection for quantitative bacteriology and histopathological analysis. RESULTS: There was a dose-effect relationship between insufflated R-PLGA and burden of bacteria in the lungs. In addition, guinea pigs treated with R-PLGA had a significantly smaller number of viable bacteria (P < 0.05), reduced inflammation and lung damage than lactose or saline control, PLGA or RIF treated animals. CONCLUSIONS: These studies indicate the potential of R-PLGA, delivered by insufflation or nebulization directly to the lungs, to affect the early development of pulmonary TB.


Assuntos
Antibióticos Antituberculose/administração & dosagem , Antibióticos Antituberculose/uso terapêutico , Sistemas de Liberação de Medicamentos , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Administração por Inalação , Aerossóis , Animais , Contagem de Colônia Microbiana , Relação Dose-Resposta a Droga , Portadores de Fármacos , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Cobaias , Indicadores e Reagentes , Ácido Láctico , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Microesferas , Mycobacterium tuberculosis , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros , Tuberculose/microbiologia , Tuberculose/patologia
9.
J Antimicrob Chemother ; 48(3): 431-4, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11533012

RESUMO

A Mycobacterium tuberculosis (H37Rv)-infected guinea pig model was used to screen for targeted delivery to the lungs by insufflation (with lactose excipient) or nebulization, of either rifampicin alone, rifampicin within poly(lactide-co-glycolide) microspheres (R-PLGA) or polymer microparticles alone (PLGA). Animals treated with single and double doses of R-PLGA microspheres exhibited significantly reduced numbers of viable bacteria, inflammation and lung damage compared with lactose-, PLGA- or rifampicin-treated animals 28 days post-infection (P < 0.05). Two doses of R-PLGA resulted in reduced splenic enlargement. These studies support the potential of R-PLGA delivered to the lung to treat pulmonary tuberculosis.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Animais , Antibióticos Antituberculose/administração & dosagem , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Cobaias , Insuflação , Masculino , Nebulizadores e Vaporizadores , Tamanho da Partícula , Rifampina/administração & dosagem , Tuberculose/patologia
10.
J Vasc Surg ; 34(1): 5-12, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11436067

RESUMO

PURPOSE: This study was undertaken to determine the safety and efficacy of reoperations for recurrent carotid stenosis (REDOCEA) at the Cleveland Clinic. MATERIALS AND METHODS: From 1989 to 1999, 206 consecutive REDOCEAs were performed in 199 patients (131 men, 68 women) with a mean age of 68 years (median, 69 years; range, 47-86 years). A total of 119 procedures (57%) were performed for severe asymptomatic stenosis, 55 (27%) for hemispheric transient ischemic attacks or amaurosis fugax, 26 (13%) for prior stroke, and 6 (3%) for vertebrobasilar symptoms. Eleven REDOCEAs (5%) were combined with myocardial revascularization, and another 19 (9%) represented multiple carotid reoperations (17 second reoperations and 2 third reoperations). Three REDOCEAs (1%) were closed primarily, and nine (4%) required interposition grafts, whereas the remaining 194 (95%) were repaired with either vein patch angioplasty (139 [68%]) or synthetic patches (55 [27%]). Three patients (2%) were lost to follow-up, but late information was available for 196 patients (203 operations) at a mean interval of 4.3 years (median, 3.9 years; maximum, 10.2 years). RESULTS: Considering all 206 procedures, there were 7 early (< 30 days) postoperative neurologic events (3.4%), including 6 perioperative strokes (2.9%) and 1 occipital hemorrhage (0.5%) on the 12th postoperative day. Seventeen additional neurologic events occurred during the late follow-up period, consisting of eight strokes (3.9%) and nine transient ischemic attacks (4.4 %). With the Kaplan-Meier method, the estimated 5-year freedom from stroke was 92% (95% CI, 88%-96%). There were two early postoperative deaths (1%), both from cardiac complications after REDOCEAs combined with myocardial revascularization procedures. With the Kaplan-Meier method, the estimated 5-year survival was 81% (range, 75%-88%). A univariate Cox regression model yielded the presence of coronary artery disease as the only variable that was significantly associated with survival (P =.024). The presence of pulmonary disease (P =.036), diabetes (P =.01), and advancing age (P =.006) was found to be significantly associated with stroke after REDOCEA. Causes of 53 late deaths were cardiovascular problems in 25 patients (47%), unknown in 14 (26%), renal failure in 4 (8%), stroke in 3 (6%), and miscellaneous in 7 (13%). CONCLUSIONS: We conclude that REDOCEA may be safely performed in selected patients with recurrent carotid stenosis and that most of these patients enjoy long-term freedom from stroke.


Assuntos
Estenose das Carótidas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Amaurose Fugaz/cirurgia , Feminino , Humanos , Ataque Isquêmico Transitório/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Reoperação , Estudos Retrospectivos , Resultado do Tratamento
12.
J Vasc Surg ; 33(4): 728-32, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11296324

RESUMO

PURPOSE: Given the uncertainties associated with carotid angioplasty and stenting, the initial assessment of the procedure may be best undertaken in a subgroup of patients at increased risk for complications with standard carotid surgery. In an effort to characterize such a subgroup, we reviewed the results of carotid endarterectomy in patients with and without significant medical comorbidity. METHODS: During a 10-year period 3061 carotid endarterectomies were performed at a single institution and entered prospectively into a registry. A high-risk patient subgroup was identified, defined by the presence of severe coronary artery disease, chronic obstructive lung disease, or renal insufficiency. The outcome of carotid endarterectomy was assessed with respect to perioperative stroke, myocardial infarction, or death, as well as the combined end point of one or more of the end points. RESULTS: The rate of the composite end point stroke/myocardial infarction/death was 3.8% in the total group of 3061 patients who underwent endarterectomy. As individual end points, the rate of stroke was 2.1%, myocardial infarction 1.2%, and death 1.1%. Among the high-risk subset, the composite end point stroke/myocardial infarction/death occurred in 7.4%. This rate was significantly greater than the corresponding rate of 2.9% in the low-risk subset (P <.0005). Similarly, the rate of stroke (3.5% vs 1.7%, P =.008) or death (4.4% vs 0.3%, P <.001) as solitary events was significantly greater in high-risk patients. CONCLUSIONS: Although carotid endarterectomy is an extremely safe procedure in most patients, results are not as favorable in a high-risk subset with severe coronary, pulmonary, or renal disease. The initial clinical evaluation of carotid stenting might best be undertaken in such a high-risk population, one that comprises patients for whom standard therapy is associated with a high rate of complications.


Assuntos
Endarterectomia das Carótidas/efeitos adversos , Angioplastia com Balão , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Estenose das Carótidas/complicações , Estenose das Carótidas/cirurgia , Estenose das Carótidas/terapia , Comorbidade , Endarterectomia das Carótidas/mortalidade , Humanos , Ataque Isquêmico Transitório/cirurgia , Infarto do Miocárdio/etiologia , Estudos Prospectivos , Fatores de Risco , Stents , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia
13.
Biochim Biophys Acta ; 1518(3): 237-48, 2001 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-11311935

RESUMO

Recently three orphan G-protein coupled receptors, RAIG1, GPRC5B and GPRC5C, with homology to members of family C (metabotropic glutamate receptor-like) have been identified. Using the protein sequences of these receptors as queries we identified overlapping expressed sequence tags which were predicted to encode an additional subtype. The full length coding regions of mouse mGprc5d and human GPRC5D were cloned and shown to contain predicted open reading frames of 300 and 345 amino acids, respectively. GPRC5D has seven putative transmembrane segments and is expressed in the cell membrane. The four human receptor subtypes, which we assign to group 5 of family C GPCRs, show 31-42% amino acid sequence identity to each other and 20-25% sequence identity to the transmembrane domains of metabotropic glutamate receptor subtypes 2 and 3 and other family C members. In contrast to the remaining family C members, the group 5 receptors have short amino terminal domains of some 30-50 amino acids. GPRC5D was shown to be clustered with RAIG1 on chromosome 12p13.3 and like RAIG1 and GPRC5B to consist of three exons, the first exon being the largest containing all seven transmembrane segments. GPRC5D mRNA is widely expressed in the peripheral system but all four receptors show distinct expression patterns. Interestingly, mRNA levels of all four group 5 receptors were found in medium to high levels in the kidney, pancreas and prostate and in low to medium levels in the colon and the small intestine, whereas other organs only express a subset of the genes. In an attempt to delineate the signal transduction pathway(s) of the orphan receptors, a series of chimeric receptors containing the amino terminal domain of the calcium sensing receptor or metabotropic glutamate receptor subtype 1, and the seven transmembrane domain of the orphan receptors were constructed and tested in binding and functional assays.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Receptores de Superfície Celular/genética , Receptores Acoplados a Proteínas G , Receptores de Glutamato Metabotrópico/genética , Proteínas Recombinantes de Fusão/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Membrana Celular/metabolismo , Clonagem Molecular , Biblioteca Gênica , Proteínas de Fluorescência Verde , Humanos , Rim/metabolismo , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Masculino , Camundongos , Dados de Sequência Molecular , Pâncreas/metabolismo , Próstata/metabolismo , Ácido Quisquálico , Receptores de Superfície Celular/química , Receptores de Glutamato Metabotrópico/química , Proteínas Recombinantes de Fusão/química , Alinhamento de Sequência , Homologia de Sequência , Transdução de Sinais , Transfecção , Tretinoína , Células Tumorais Cultivadas
14.
AIDS Educ Prev ; 13(1): 42-54, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11252453

RESUMO

Lifetime and current health practices and risk behaviors were examined among 350 youth living with HIV (YLH) aged 14-23 years from four AIDS epicenters (72.6% male; 26.2% African American, 36.9% Latino). YLH were relatively healthy (M CD4 cells = 499), had used substantial health care and were satisfied with the care. YLH's sexual and substance-use histories indicated substantial HIV related risk acts: the median number of lifetime partners was 25 with only 8% using condoms consistently; 14.9% had injected drugs, and 61.2% had used hard drugs. Compared with females, males had more lifetime and recent sexual partners and had used more drugs. Youth who were recently sexually active (81.3%) had multiple partners. Most of the sexually active YLH used condoms consistently (81.6%). YLH who were symptomatic or had an AIDS diagnosis were likely to have recently had more seropositive sexual partners than the asymptomatic youth. Youth disclosed their serostatus to about half of their sexual partners (53.9%). YLH with AIDS used fewer hard drugs than those without an AIDS diagnosis. Health and risk behaviors of the YLH varied significantly based on their disease stage, gender, and ethnicity, suggesting the need for tailoring interventions for subgroups of YLH.


Assuntos
Comportamento do Adolescente , Infecções por HIV/psicologia , Assunção de Riscos , Adolescente , Adulto , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Psicologia do Adolescente , Fatores de Risco , Sexo Seguro/etnologia , Sexo Seguro/psicologia , Comportamento Sexual/etnologia , Comportamento Sexual/psicologia , Abuso de Substâncias por Via Intravenosa/complicações , Estados Unidos/epidemiologia , Estados Unidos/etnologia
15.
FEBS Lett ; 488(1-2): 18-22, 2001 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-11163788

RESUMO

In young expanding leaves of Brassica napus, the demand for fatty acids is met by de novo biosynthesis of fatty acid synthase components, as demonstrated by 3-oxoacyl-ACP reductase. Using a novel radio-chemical assay for 3-oxoacyl-ACP reductase and specific antibodies, we have demonstrated a direct relationship between the increase in activity and synthesis of polypeptide. The maximum rate of fatty acid synthesis was between 4 and 7 days post-emergence, but slowed after this point even though 3-oxoacyl-ACP reductase activity was high. Leaf area continued to expand in a linear fashion after reductions in both enzyme activity and the rate of fatty acid synthesis.


Assuntos
Oxirredutases do Álcool/metabolismo , Brassica/crescimento & desenvolvimento , Brassica/metabolismo , Ácidos Graxos/biossíntese , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , 3-Oxoacil-(Proteína Carreadora de Acil) Redutase , Brassica/citologia , Brassica/enzimologia , Extratos Celulares , Ácidos Graxos/análise , Cinética , Folhas de Planta/citologia , Folhas de Planta/enzimologia , Espectrofotometria , Trítio
16.
J Vasc Surg ; 33(1): 63-71, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11137925

RESUMO

OBJECTIVE: The aim of the study was to evaluate the safety and efficacy of percutaneous angioplasty and stenting (PAS) in comparison with traditional open surgical (OS) revascularization for the treatment of chronic mesenteric ischemia. METHODS: Over a 3.5-year period, 28 patients (32 vessels) underwent PAS (balloon angioplasty alone, 5 [18%] of 28; angioplasty and stenting, 23 [82%] of 28) for symptoms of chronic mesenteric ischemia. These patients were compared with a previously published series of 85 patients (130 vessels) treated with OS (bypass grafting, 60 [71%] of 85; transaortic endarterectomy, 19 [22%] of 85; or patch angioplasty, 6 [7%] of 85). RESULTS: The PAS and OS groups were similar with respect to baseline comorbidities, duration of symptoms (median: 6.7 vs 10.5 months, P =.52), and the number of vessels involved, but the patients differed in their age at presentation (median: 72 vs 65 years, P =.005). Fewer vessels were revascularized per patient in the PAS group (1.1 +/- 0.4) compared with the OS group (1.5 +/- 0.6, P =.001). Overall, 85.7% (24/28) had one vessel and 14.3% (4/28) had two vessels revascularized in the PAS group versus 48.2% (41/85) with one-vessel and 47.1% (40/85) with two-vessel revascularization in the OS group. No difference was noted in the early in-hospital complications (median: 17.9% [PAS] vs 32.9% [OS], P =.12) or mortality rate (10.7% [PAS] vs 8.2% [OS], P =.71). A reduced length of hospital stay in the PAS patients did not attain statistical significance (median: 5 days [PAS] vs 13 days [OS], P =.08). Although the 3-year cumulative recurrent stenosis (P =.62) and mortality rate (P =.99) did not differ, the PAS treatment group had a higher incidence of recurrent symptoms (P =.001). CONCLUSION: Although the results of PAS and OS were similar with respect to morbidity, death, and recurrent stenosis, PAS was associated with a significantly higher incidence of recurrent symptoms. These findings suggest that OS should be preferentially offered to patients deemed fit for open revascularization.


Assuntos
Angioplastia com Balão , Intestinos/irrigação sanguínea , Isquemia/terapia , Oclusão Vascular Mesentérica/terapia , Stents , Procedimentos Cirúrgicos Vasculares , Idoso , Implante de Prótese Vascular , Doença Crônica , Endarterectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Recidiva , Resultado do Tratamento
17.
J Biol Chem ; 276(13): 10110-8, 2001 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-11133983

RESUMO

The metabotropic glutamate receptors (mGluRs) belong to family C of the G-protein-coupled receptor (GPCR) superfamily. The receptors are characterized by having unusually long amino-terminal domains (ATDs), to which agonist binding has been shown to take place. Previously, we have constructed a molecular model of the ATD of mGluR1 based on a weak amino acid sequence similarity with a bacterial periplasmic binding protein. The ATD consists of two globular lobes, which are speculated to contract from an "open" to a "closed" conformation following agonist binding. In the present study, we have created a Zn(2+) binding site in mGluR1b by mutating the residue Lys(260) to a histidine. Zinc acts as a noncompetitive antagonist of agonist-induced IP accumulation on the K260H mutant with an IC(50) value of 2 microm. Alanine mutations of three potential "zinc coligands" in proximity to the introduced histidine in K260H knock out the ability of Zn(2+) to antagonize the agonist-induced response. Zn(2+) binding to K260H does not appear to affect the dimerization of the receptor. Instead, we propose that binding of zinc has introduced a structural constraint in the ATD lobe, preventing the formation of a "closed" conformation, and thus stabilizing a more or less inactive "open" form of the ATD. This study presents the first metal ion site constructed in a family C GPCR. Furthermore, it is the first time a metal ion site has been created in a region outside of the seven transmembrane regions of a GPCR and the loops connecting these. The findings offer valuable insight into the mechanism of ATD closure and family C receptor activation. Furthermore, the findings demonstrate that ATD regions other than those participating in agonist binding could be potential targets for new generations of ligands for this family of receptors.


Assuntos
Receptores de Glutamato Metabotrópico/química , Receptores de Glutamato Metabotrópico/metabolismo , Zinco/metabolismo , Alanina/química , Animais , Sítios de Ligação , Western Blotting , Células CHO , Linhagem Celular , Membrana Celular/metabolismo , Cloretos/farmacologia , Cricetinae , Relação Dose-Resposta a Droga , Ácido Glutâmico/metabolismo , Histidina/química , Humanos , Immunoblotting , Concentração Inibidora 50 , Fosfatos de Inositol/metabolismo , Íons , Cinética , Ligantes , Lisina/química , Modelos Moleculares , Mutação , Plasmídeos/metabolismo , Mutação Puntual , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , Transfecção , Zinco/química , Compostos de Zinco/farmacologia
18.
Pharm Res ; 17(8): 955-61, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11028941

RESUMO

PURPOSE: Particles with aerodynamic diameters of 1-5 microm deposit in the periphery of the lungs and are phagocytized by alveolar macrophages, the primary site of Mycobacterium tuberculosis infection. Aerosols of biodegradable polymeric microspheres containing antitubercular agents may be delivered to the lungs to improve the treatment of tuberculosis. METHODS: Poly(lactide-co-glycolide) (PLGA) microspheres containing rifampicin were prepared using solvent evaporation and spray drying methods. The solvent evaporation process was optimized using factorial experimental design and surface response methodology. The morphology, particle size, drug loading, and dissolution of microspheres was evaluated. RESULTS: The spray dried rifampicin loaded PLGA microparticles were shriveled, unlike the spherical particles produced by solvent evaporation. Drug loadings of 20% and 30% were achieved for solvent evaporation and spray dried products, respectively. The particles prepared by solvent evaporation and spray drying had 3.45 microm and 2.76 microm median diameters by volume, respectively. CONCLUSIONS: Respirable rifampicin loaded PLGA microspheres were produced by both solvent evaporation and spray drying methods. These particles are being evaluated in an animal model of tuberculosis.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Ácido Láctico , Ácido Poliglicólico , Polímeros , Rifampina/uso terapêutico , Antibióticos Antituberculose/administração & dosagem , Soluções Tampão , Dessecação , Portadores de Fármacos , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Rifampina/administração & dosagem , Solventes , Propriedades de Superfície
19.
J Vasc Surg ; 32(4): 770-6, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11013041

RESUMO

BACKGROUND: Endovascular grafting has markedly reduced the invasiveness of the treatment of abdominal aortic aneurysms. By using a modification of technique for available closure devices, we have been able to achieve percutaneous repair of aneurysms. This study reviewed our initial experience with this technique. METHODS: Demographics and background data from patients undergoing endovascular repair of abdominal aortic aneurysms were reviewed from prospectively collected registry data. Operative notes and angiographic and computed tomography scan data were retrospectively reviewed to assess the success of the percutaneous approach. RESULTS: Fourteen patients have undergone percutaneous placement of the AneuRx (Medtronic, Sunnyvale, Calif) endovascular graft, with a modification of the technique for the Prostar (Perclose, Redwood City, Calif) device for access site closure. Main graft body introduction with a 22F sheath proved successful in nine of 12 (75%) deployments. Contralateral limb deployment through a 16F sheath was successful in 10 of 14 deployments (71.4%). Reasons for conversion to open groin incisions include inadequate percutaneous hemostasis (six cases), iliofemoral dissection (four cases), device failure (one case), and compromised distal flow (one case). Percutaneous deployment success appears to be improved with larger iliac artery dimensions, decreased calcification, and limited tortuosity, because of the limitation of complications related to delivering a larger diameter sheath. Of the 13 percutaneous endograft insertions that were attempted, six (46.2%) were completely successful. CONCLUSION: Percutaneous deployment of available devices is technically feasible by using modifications of technique with percutaneous closure devices, despite large introducer sizes. Further experience with this technique offers the potential for identifying patients in whom this will prove successful and for even further reducing hospital stay and recovery times for aneurysm repair.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/métodos , Stents , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Sutura
20.
J Vasc Surg ; 32(3): 602-6, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10957670

RESUMO

From 1995 through 1998, we encountered eight patients with infected Dacron patches after previous carotid endarterectomy. Two of the original operations had been done elsewhere, but the six patients who were collected from our own series represented 0.5% of the 1258 carotid endarterectomies we performed and 1.8% of the 340 synthetic carotid patches we applied without any comparable infections among another 918 patients who received either vein patch angioplasty (n = 843) or primary arteriotomy closure (n = 74) during the same 4-year study period. With a single exception ("no growth"), bacterial cultures that were obtained at the time of the eight reoperations revealed Staphylococcus (n = 4) or Streptococcus (n = 3) species. All of the infected Dacron patches were removed and were replaced with saphenous vein patches (n = 5) or interposition grafts (n = 3), after which appropriate oral (n = 2) or intravenous (n = 6) antibiotics were administered for 2 to 6 weeks. No postoperative deaths occurred, but there were 2 temporary cranial nerve injuries, 1 myocardial infarction, and 1 stroke that was related to preoperative angiography. A recurrent carotid infection has not developed in any of the eight patients during a mean follow-up interval of 16 months (range, 3-36 months).


Assuntos
Prótese Vascular , Endarterectomia das Carótidas , Polietilenotereftalatos , Infecções Relacionadas à Prótese/cirurgia , Infecções Estafilocócicas/cirurgia , Infecções Estreptocócicas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/diagnóstico por imagem , Radiografia , Reoperação , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estreptocócicas/diagnóstico por imagem , Veias/transplante
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