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1.
Proc Biol Sci ; 287(1919): 20192478, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31964300

RESUMO

Evolutionary demography predicts that variation in reproductive timing stems from socio-ecologically contingent trade-offs between current and future reproduction. In contemporary high-income societies, the costs and benefits of current reproduction are likely to vary by socioeconomic status (SES). Two influential hypotheses, focusing on the parenthood 'wage penalty', and responses to local mortality have separately been proposed to influence the timing of parenthood. Economic costs of reproduction (i.e. income loss) are hypothesized to delay fertility, especially among high childhood SES individuals who experience greater opportunities to build capital through advantageous education and career opportunities. On the other hand, relatively low childhood SES individuals experience higher mortality risk, which may favour earlier reproduction. Here, we examine both hypotheses with a representative register-based, multigenerational dataset from contemporary Finland (N = 47 678). Consistent with each hypothesis, the predicted financial cost of early parenthood was smaller, and mortality among close kin was higher for individuals with lower childhood SES. Within the same dataset, lower predicted adulthood income and more kin deaths were also independently associated with earlier parenthood. Our results provide a robust demonstration of how economic costs and mortality relate to reproductive timing. We discuss the implications of our findings for demographic theory and public policy.


Assuntos
Morte , Reprodução , Classe Social , Adulto , Fatores Etários , Criança , Demografia , Finlândia , Humanos , Renda , Salários e Benefícios , Fatores Socioeconômicos
2.
Perfusion ; 32(2): 97-109, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27708000

RESUMO

Modified ultrafiltration (MUF) is a technique which is commonly used immediately post-cardiopulmonary bypass (CPB) for open heart surgery in children. There are many advantages of MUF, but there are also a number of less reported disadvantages. At our institution, after considering all of the available data, a decision was made to no longer perform MUF. The primary motivation being the simplified and miniaturized CPB circuit would reduce hemodilution, decrease our likelihood of reaching our transfusion trigger during CPB and, potentially, improve safety. This study reports the before and after data from this practice change. A total of 160 patients less than 8kg were studied over 38 months and divided into neonatal and pediatric cohorts. Parameters reported in this study include: demographics, hematocrit, blood product transfusion, hemostasis, hemodynamics and outcomes. Although retrospective, our analysis supports an advantage of preventing hemodilution (via circuit miniaturization) versus reversing hemodilution (via MUF) at our institution with the patient population we examined.


Assuntos
Ponte Cardiopulmonar/métodos , Parada Cardíaca Induzida/métodos , Ultrafiltração/métodos , Transfusão de Sangue , Ponte Cardiopulmonar/instrumentação , Desenho de Equipamento , Parada Cardíaca Induzida/instrumentação , Hematócrito , Hemodinâmica , Hemostasia , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos , Ultrafiltração/instrumentação
3.
Perfusion ; 32(4): 264-268, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27856841

RESUMO

BACKGROUND: Current blood pumps used for cardiopulmonary bypass generally fall into two different pump design categories; non-occlusive centrifugal pumps and occlusive, positive-displacement roller pumps. The amount of foreign surface area of extracorporeal circuits correlates with post-operative morbidity due to systemic inflammation, leading to a push for technology that reduces the amount of foreign surfaces. Current roller pumps are bulky and the tubing forms an arc in the pumping chamber (raceway), positioning the inlet 360 degrees from the outlet, making it very difficult to place the pump closer to the patient and to efficiently reduce tubing length. These challenges put existing roller pumps at a disadvantage for use in a compact cardiopulmonary bypass circuit. Centrifugal blood pumps are easier to incorporate into miniature circuit designs. However, the prime volumes of current centrifugal pump designs are large, especially for pediatric extracorporeal circuits where the prime volumes are too great to be of clinical value. METHOD: We describe a preliminary report on a novel, occlusive, linear, single-helix, positive-displacement blood pump which allows for decreased prime volume and surface area of the extracorporeal circuit. This new experimental pump design was used to perfuse a 6 kilogram piglet with a pediatric cardiopulmonary bypass circuit for two hours of continuous use. Blood samples were obtained every thirty minutes and assayed for plasma free hemolysis generation. CONCLUSIONS: The results from this initial experiment showed low plasma free hemoglobin generation and encourages the authors to further develop this concept.


Assuntos
Ponte Cardiopulmonar/instrumentação , Ponte Cardiopulmonar/métodos , Coração Auxiliar , Animais , Feminino , Hemólise , Suínos
4.
Semin Cardiothorac Vasc Anesth ; 18(2): 153-60, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24876230

RESUMO

There have been numerous recent advances geared specifically toward the practice of pediatric cardiopulmonary bypass (CPB). These advances include the development of the first oxygenator intended solely for the neonatal CPB patient; pediatric oxygenators with low prime volumes and surface areas, which allow flows up to 2 L/min; pediatric oxygenators with integrated arterial filters; and miniature ultrafiltration (UF) devices, which allow for high rates of ultrafiltrate removal. When used in combination with heart lung machines with mast-mounted pumps, these advances can result in significant decreases in CPB circuit surface areas and prime volumes. This may attenuate CPB-associated hemodilution and decrease or eliminate the need for homologous red blood cells during or after CPB. In addition to these equipment-related advances, changes in myocardial protection strategies and the technique of modified UF as it relates to these advances are discussed.


Assuntos
Ponte Cardiopulmonar/métodos , Criança , Parada Cardíaca Induzida , Humanos , Oxigenadores , Ultrafiltração
5.
J Extra Corpor Technol ; 45(2): 107-11, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23930379

RESUMO

UNLABELLED: The timing of blood product administration after cardiopulmonary bypass (CPB) may influence the amount of postoperative transfusion and chest tube output. We performed a retrospective study of a novel technique of administering blood products during modified ultrafiltration (MUF) in congenital cardiac surgery. A Control Group (CG; n = 55) received cryoprecipitate and platelets after modified ultrafiltration. The Treatment Group (TG; n = 59) received cryoprecipitate and platelets during MUF. Volumes of blood products transfused in the operating room, initial coagulation parameters in the cardiac intensive care unit, and first 24-hour chest tube output were recorded. Age (116 +/- 198 versus 84 +/- 91 days), weight (4.6 +/- 1.8 versus 4.5 +/- 1.4 kg), duration of bypass (121 +/- 50 versus 139 +/- 57 minutes), and Aristotle scoring (9.3 +/- 2.7 versus 9.1 +/- 3.1) were not significantly different when comparing the control and treatment groups, respectively. Intraoperative packed red blood cells (74.4 +/- 34.8 versus 79.3 +/- 58.0 mL/kg, p = .710), fresh-frozen plasma (58.3 +/- 27.1 versus 59.1 +/- 27.2 mL/kg, p = .849), cryoprecipitate (7.3 +/- 5.1 versus 8.6 +/- 5.9 mL/kg, p = .109), and platelet (19.0 +/- 14.6 versus 23.7 +/- 20.8 mL/kg, p = .176) administration were the same in the control and treatment groups, respectively. However, fibrinogen levels on arrival in the coronary intensive care unit were significantly higher (305 +/- 80 versus 255 +/- 40 mg/dL, p < .001) in the CG compared with the TG. Twenty-four-hour chest tube output was not significantly different but the CG (17.76 +/- 9.34 mL/kg/24 hours) was trending lower than the TG (19.52 +/- 10.94 mL/kg/24 hours, p = .357). In an attempt to minimize CPB-associated bleeding and transfusions, we changed our practice by adjusting the timing of blood product administration after patient separation from CPB. The goals of the change in practice were not measurably different in terms of shorter intraoperative times, fewer blood transfusions, or less chest tube output at our institution. KEYWORDS: congenital heart disease, modified ultrafiltration, cryoprecipitate, platelets, cardiopulmonary bypass.


Assuntos
Ponte Cardiopulmonar/instrumentação , Fator VIII/administração & dosagem , Fibrinogênio/administração & dosagem , Cardiopatias Congênitas/enfermagem , Cardiopatias Congênitas/cirurgia , Hemofiltração/instrumentação , Transfusão de Plaquetas/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Lactente , Masculino
6.
Pediatr Res ; 74(4): 413-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23863853

RESUMO

BACKGROUND: The utility of procalcitonin (PCT) and C-reactive protein (CRP) as infectious biomarkers following infant cardiothoracic surgery is not well defined. METHODS: We designed a prospective cohort study to evaluate PCT and CRP after infant cardiothoracic surgery. PCT and CRP were drawn preoperatively and 24/72 h postoperation or daily in delayed sternal closure patients. Presence of infection within 10 d of surgery, vasoactive-inotropic scores at 24 and 72 h, and length of intubation, intensive care unit stay, and hospital stay were documented. RESULTS: PCT and CRP were elevated at 24 h. PCT then decreased while CRP increased in patients undergoing delayed sternal closure or cardiopulmonary bypass. In the delayed sternal closure group, PCT was significantly higher on postoperative days 2-5 in patients who ultimately developed infection. Higher PCT was independently associated with increased vasoactive-inotropic score at 72 h. CRP did not correlate with infection or postoperative support. CONCLUSION: PCT rises after cardiothoracic surgery in infants but decreases by 72 h while CRP remains elevated. Sternal closure may affect CRP but not PCT. PCT is independently associated with circulatory support requirements at 72 h postoperation and with development of infection. PCT may have greater utility as a biomarker in this population.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Complicações Pós-Operatórias/sangue , Precursores de Proteínas/sangue , Sepse/sangue , Análise de Variância , Peptídeo Relacionado com Gene de Calcitonina , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Cinética , Modelos Lineares , Testes de Função Hepática , Estudos Prospectivos , Estatísticas não Paramétricas , Fatores de Tempo
7.
J Hosp Infect ; 84(3): 215-21, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23706671

RESUMO

BACKGROUND: External cerebrospinal fluid (CSF) diversion via a drain is associated with a variable risk of associated infections which cause significant morbidity. AIM: To establish whether simple interventions can reduce the incidence of such infections at a single centre. METHODS: A retrospective review of all patients undergoing an external CSF diversion procedure was carried out to determine the historical rate of infection. Following an institutional protocol which included standards on drain insertion, care, sampling and antibiotic prescribing a prospective study was carried out to observe whether infection rates had changed and which factors continued to predict drain-related infections. FINDINGS: Retrospective analysis identified 234 procedures in 159 patients over a two-year period. There were 54 drain-related infections, a rate of 21.5 per 1000 drainage days. Duration of CSF drainage [odds ratio (OR) = 1.15, P < 0.05] and the number of CSF samples taken per drain (OR = 5.98, P < 0.05) were independently associated with infection. In the prospectively gathered phase, 132 procedures were recorded in 107 patients over a one-year period. There were 18 infections, a rate of 13.7 per 1000 drainage days. The only independent prognostic factor was duration of CSF drainage (OR = 1.20, P < 0.05). Coagulase-negative staphylococci were the most commonly isolated type of organism in both series. CONCLUSION: Ensuring drains are removed promptly as soon as CSF diversion is no longer required may reduce the rate of nosocomial infections in this population despite multiple confounding factors. Institutional guidelines may promote best practice in this regard.


Assuntos
Infecções do Sistema Nervoso Central/prevenção & controle , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Líquido Cefalorraquidiano/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Ann Thorac Surg ; 95(6): 2140-6; discussion 2146-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23506632

RESUMO

BACKGROUND: Rapid-response extracorporeal membrane oxygenation (RR-ECMO) has been implemented at select centers to expedite cannulation for patients placed on ECMO during extracorporeal cardiopulmonary resuscitation (ECPR). In 2008, we established such a program and used it for all pediatric venoarterial ECMO initiations. This study was designed to compare outcomes before and after program implementation. METHODS: Between 2003 and 2011, 144 pediatric patients were placed on venoarterial ECMO. Records of patients placed on ECMO before (17 ECPR and 62 non-ECPR) or after (14 ECPR and 51 non-ECPR) RR-ECMO program implementation were retrospectively compared. RESULTS: The peak performance of the ECMO team was assessed by measuring ECMO initiation times for the ECPR patient subgroup (n = 31). There was a shift toward more ECPR initiations achieved in less than 40 minutes (24% pre-RR-ECMO versus 43% RR-ECMO; p = 0.25) and fewer requiring more than 60 minutes (47% pre-RR-ECMO versus 21% RR-ECMO; p = 0.14) after program implementation, although these changes did not reach statistical significance. After multivariable risk adjustment, RR-ECMO was associated with a 52% reduction in neurologic complications for all patients (adjusted odds ratio, 0.48; 95% confidence interval, 0.23 to 0.98; p = 0.04), but the risk of in-hospital death remained unchanged (adjusted odds ratio, 0.99; 95% confidence interval, 0.50 to 1.99; p = 0.99). CONCLUSIONS: Implementation of a pediatric RR-ECMO program for venoarterial ECMO initiation was associated with reduced neurologic complications but not improved survival during the first 3 years of program implementation. These data suggest that development of a coordinated system for rapid ECMO deployment may benefit both ECPR and non-ECPR patients, but further efforts are required to improve survival.


Assuntos
Oxigenação por Membrana Extracorpórea/mortalidade , Oxigenação por Membrana Extracorpórea/métodos , Parada Cardíaca/terapia , Mortalidade Hospitalar/tendências , Equipe de Respostas Rápidas de Hospitais/organização & administração , Reanimação Cardiopulmonar/métodos , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Implementação de Plano de Saúde/organização & administração , Parada Cardíaca/mortalidade , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Masculino , Pediatria/organização & administração , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
9.
Crit Care ; 16(4): R160, 2012 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-22906145

RESUMO

INTRODUCTION: Limited evidence suggests that serum alkaline phosphatase activity may decrease after cardiac surgery in adults and children. The importance of this finding is not known. Recent studies, however, have identified a potential role for alkaline phosphatase as modulator of inflammation in multiple settings, including during adult cardiopulmonary bypass. We sought to describe the change in alkaline phosphatase activity after cardiothoracic surgery in infants and to assess for a correlation with intensity and duration of post-operative support, markers of inflammation, and short-term clinical outcomes. METHODS: Sub-analysis of a prospective observational study on the kinetics of procalcitonin in 70 infants (≤ 90 days old) undergoing cardiothoracic surgery. Subjects were grouped based on the use of cardiopulmonary bypass and delayed sternal closure. Alkaline phosphatase, procalcitonin, and C-reactive protein (CRP) levels were obtained pre-operation and on post-operative day 1. Mean change in alkaline phosphatase activity was determined in each surgical group. Generalized linear modeling and logistic regression were employed to assess for associations between post-operative alkaline phosphatase activity and post-operative support, inflammation, and short term outcomes. Primary endpoints were vasoactive-inotropic score at 24 hours and length of intubation. Secondary endpoints included procalcitonin/CRP levels on post-operative day 1, length of hospital stay, and cardiac arrest or death. RESULTS: Mean decrease in alkaline phosphatase was 30 U/L (p = 0.01) in the non-bypass group, 114 U/L (p < 0.0001) in the bypass group, and 94 U/L (p < 0.0001) in the delayed sternal closure group. On multivariate analysis, each 10 U/L decrease in alkaline phosphatase activity on post-operative day 1 was independently associated with an increase in vasoactive-inotropic score by 0.7 (p < 0.0001), intubation time by 6% (p < 0.05), hospital stay by 5% (p < 0.05), and procalcitonin by 14% (P < 0.01), with a trend towards increased odds of cardiac arrest or death (OR 1.3; p = 0.06). Post-operative alkaline phosphatase activity was not associated with CRP (p = 0.7). CONCLUSIONS: Alkaline phosphatase activity decreases after cardiothoracic surgery in infants. Low post-operative alkaline phosphatase activity is independently associated with increased procalcitonin, increased vasoactive/inotropic support, prolonged intubation time, and prolonged hospital stay. Alkaline phosphatase may serve as a biomarker and potential modulator of post-operative support and inflammation following cardiothoracic surgery in infants.


Assuntos
Fosfatase Alcalina/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Inflamação/enzimologia , Cuidados Pós-Operatórios , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina , Cardiotônicos/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/etiologia , Intubação Intratraqueal , Tempo de Internação , Masculino , Estudos Prospectivos , Precursores de Proteínas/sangue
10.
Sci Total Environ ; 424: 337-43, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22449416

RESUMO

Many tonnes of compost are generated per year due to door step composting of both garden and kitchen waste. Whilst there are commercial outlets for the finer grade of compost (<10mm) in plant nurseries, there is little demand for the coarser material (>25 mm). This paper reports part of a WRAP-sponsored (Waste Resources Action Programme) study which investigated the potential for green (GC) and mixed green and food (MC) composts to be incorporated into Sustainable Drainage (SUDS) devices such as swales, and replace the topsoil (TS) onto which turf is laid or grass seed distributed. However, it is not known whether compost can replace TS in terms of pollutant remediation, both the trapping of polluted particulates and in dealing with hydrocarbons such as oil, but also from a biofilm development and activity perspective. Using laboratory based experiments utilising leaching columns and an investigation of microbiological development in the composts studied, it was found that many of the differences in performance between MC and GC were insignificant, whilst both composts performed better in terms of pollutant retention than TS. Mixed compost in particular could be used in devices where there may be oil spillages, such as the lorry park of a Motorway Service Area due to its efficiency in degrading oil. Samples of GC and MC were found to contain many of the bacteria and fungi necessary for an active and efficient biofilm which would be an argument in their favour for replacement of TS and incorporation in swales.


Assuntos
Biofilmes/crescimento & desenvolvimento , Recuperação e Remediação Ambiental/métodos , Microbiologia do Solo , Solo/análise , Poluentes Químicos da Água/metabolismo , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Conservação dos Recursos Naturais , Fungos/classificação , Fungos/crescimento & desenvolvimento , Fungos/isolamento & purificação , Reino Unido , Qualidade da Água , Áreas Alagadas
11.
J Extra Corpor Technol ; 43(3): 157-61, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22164455

RESUMO

The use of smaller cannulae for minimally invasive surgery techniques and/or aggressive miniaturization of the cardiopulmonary bypass (CPB) circuitry has necessitated the need to augment venous drainage to achieve adequate flow rates. Vacuum assisted venous drainage (VAVD) has become the dominant method to augment venous drainage. VAVD, however, has been associated with a number of known side effects including increased transmission of gaseous microemboli to the patient, venous line chatter, and increased arterial to venous shunts in the circuit. Historically, our practice has been to monitor the arterial output flow rate and to monitor VAVD by observing venous line chatter and changes in the venous reservoir level. In 2008 our pediatric cardiothoracic service began monitoring venous line flow rates by using a second ultrasonic flow probe placed on the venous line. After 12 months, our staff perfusionists reviewed the impact of monitoring venous line flow rates on VAVD and its known side effects on daily clinical practice. When monitoring venous line flow rates, empiric observation revealed that less overall vacuum pressure was needed for our CPB cases. This novel approach to monitoring venous drainage has aided us in providing optimal vacuum levels and therefore, may reduce some of the known side effects experienced with excessive VAVD.


Assuntos
Ponte Cardiopulmonar/métodos , Ultrassom/instrumentação , Veias/fisiologia , Velocidade do Fluxo Sanguíneo , Ponte Cardiopulmonar/instrumentação , Humanos , Sucção
12.
J Vasc Surg ; 54(3 Suppl): 50S-4S, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21872117

RESUMO

Conflicts of interest exist when an arrangement potentially exerts inappropriate influence on decision making or professional judgment, or is perceived to do so, and can thus damage the public trust and undermine the integrity of those decisions. Concerns regarding financial conflicts of interest in the medical arena have reached their height as of late, given that physicians now function in a milieu of complex and delicate relationships with pharmaceutical, biotechnology, and medical device industries. Even when such relationships do not correlate with actual compromise of judgment or patient care, it threatens the credibility of both the health care professional and the institution because of the social perception of the effect of these relationships. Although most institutions in the Western world set forth a code of ethics and conflict-of-interest policies to be followed under threat of termination, the Veterans Health Administration (VHA) presents itself as a unique environment in which conflicts of interest are subject to governmental laws, violation of which may not only result in employment-related discipline, but may be sanctioned by civil and criminal penalties. Moreover, these provisions are developed by a national authoritative organization rather than being institution-specific guidelines. Given that many academic physicians working within the VHA may also have a component of their practice in a University setting, it becomes important to understand the differences in policy between these contexts so as not to threaten the public trust in the veracity of decisions made and, therefore, maintain the integrity of the relationship between physician and patient. This article will review aspects of conflict-of-interest policies in the realm of research, financial relationships, foreign travel, and vendor contracting that are particular to the VHA and make it a unique environment to function in as a physician and scientist.


Assuntos
Conflito de Interesses , Setor de Assistência à Saúde , Relações Interinstitucionais , Relações Interprofissionais , Qualidade da Assistência à Saúde , United States Department of Veterans Affairs , Códigos de Ética , Conflito de Interesses/economia , Conflito de Interesses/legislação & jurisprudência , Comportamento Cooperativo , Difusão de Inovações , Honorários e Preços , Doações , Regulamentação Governamental , Guias como Assunto , Setor de Assistência à Saúde/economia , Setor de Assistência à Saúde/ética , Setor de Assistência à Saúde/legislação & jurisprudência , Setor de Assistência à Saúde/normas , Política de Saúde , Humanos , Relações Interprofissionais/ética , Padrões de Prática Médica , Qualidade da Assistência à Saúde/economia , Qualidade da Assistência à Saúde/ética , Qualidade da Assistência à Saúde/legislação & jurisprudência , Qualidade da Assistência à Saúde/normas , Má Conduta Científica , Estados Unidos , United States Department of Veterans Affairs/economia , United States Department of Veterans Affairs/ética , United States Department of Veterans Affairs/legislação & jurisprudência , United States Department of Veterans Affairs/normas
13.
Br J Cancer ; 105(3): 346-52, 2011 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-21750555

RESUMO

BACKGROUND: α(v) integrins are involved in angiogenesis and melanoma tumourigenesis. Intetumumab (CNTO 95) is a fully human anti-α(v)-integrin monoclonal antibody. METHODS: In a multicentre, randomised, phase II study, stage IV melanoma patients were randomised 1:1:1:1 to 1000 mg m(-2) dacarbazine+placebo (n=32), 1000 mg m(-2) dacarbazine+10 mg kg(-1) intetumumab (n=32), 10 mg kg(-1) intetumumab (n=33), or 5 mg kg(-1) intetumumab (n=32) q3w. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), adverse events, and pharmacokinetics. RESULTS: No statistically significant differences in efficacy were observed between groups. In the dacarbazine+placebo, dacarbazine+intetumumab, 10 mg kg(-1) intetumumab, and 5 mg kg(-1) intetumumab groups, median PFS was 1.8, 2.5, 1.4, and 1.4 months; median OS was 8, 11, 15, and 9.8 months; and ORR of complete+partial response was 10, 3, 6, and 0%. Nonlinear intetumumab pharmacokinetics and potential intetumumab-dacarbazine interactions were observed. Transient, asymptomatic, nonrecurring, grade 1-2, uveitic reactions that resolved spontaneously or with topical steroids were seen in 22-30% of intetumumab-treated patients. Low-grade infusion-reaction symptoms (headache, fatigue, nausea, vomiting, fever, chills) were observed, as expected, in 16-73% of dacarbazine-treated patients. No intetumumab-related myelosuppression, laboratory/electrocardiogram abnormalities, or deaths occurred. CONCLUSION: With its favourable safety profile and a nonsignificant trend towards improved OS, intetumumab merits further investigation in advanced melanoma.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/administração & dosagem , Integrina alfaV/imunologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Uveíte/induzido quimicamente
14.
Science ; 330(6003): 512-4, 2010 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-20966253

RESUMO

The Afrotropical mosquito Anopheles gambiae sensu stricto, a major vector of malaria, is currently undergoing speciation into the M and S molecular forms. These forms have diverged in larval ecology and reproductive behavior through unknown genetic mechanisms, despite considerable levels of hybridization. Previous genome-wide scans using gene-based microarrays uncovered divergence between M and S that was largely confined to gene-poor pericentromeric regions, prompting a speciation-with-ongoing-gene-flow model that implicated only about 3% of the genome near centromeres in the speciation process. Here, based on the complete M and S genome sequences, we report widespread and heterogeneous genomic divergence inconsistent with appreciable levels of interform gene flow, suggesting a more advanced speciation process and greater challenges to identify genes critical to initiating that process.


Assuntos
Anopheles/genética , Especiação Genética , Genoma de Inseto , Animais , Anopheles/classificação , Evolução Molecular , Feminino , Fluxo Gênico , Masculino , Modelos Genéticos , Polimorfismo de Nucleotídeo Único
15.
Nucleic Acids Res ; 38(Database issue): D563-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19884133

RESUMO

Ensembl Genomes (http://www.ensemblgenomes.org) is a new portal offering integrated access to genome-scale data from non-vertebrate species of scientific interest, developed using the Ensembl genome annotation and visualisation platform. Ensembl Genomes consists of five sub-portals (for bacteria, protists, fungi, plants and invertebrate metazoa) designed to complement the availability of vertebrate genomes in Ensembl. Many of the databases supporting the portal have been built in close collaboration with the scientific community, which we consider as essential for maintaining the accuracy and usefulness of the resource. A common set of user interfaces (which include a graphical genome browser, FTP, BLAST search, a query optimised data warehouse, programmatic access, and a Perl API) is provided for all domains. Data types incorporated include annotation of (protein and non-protein coding) genes, cross references to external resources, and high throughput experimental data (e.g. data from large scale studies of gene expression and polymorphism visualised in their genomic context). Additionally, extensive comparative analysis has been performed, both within defined clades and across the wider taxonomy, and sequence alignments and gene trees resulting from this can be accessed through the site.


Assuntos
Biologia Computacional/métodos , Bases de Dados Genéticas , Bases de Dados de Ácidos Nucleicos , Animais , Biologia Computacional/tendências , Expressão Gênica , Genoma Bacteriano , Genoma Fúngico , Genoma de Planta , Armazenamento e Recuperação da Informação/métodos , Internet , Invertebrados/genética , Polimorfismo Genético , Estrutura Terciária de Proteína , Software
16.
J Econ Entomol ; 102(3): 1032-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19610416

RESUMO

The psyllid Bactericera cockerelli (Sulc) (Hemiptera: Psyllidae) is the vector of a bacterial pathogen causing zebra chip (ZC) disease in potato, Solanum tuberosum L. (Solanaceae). Recently, ZC has become important to potato growers and the potato chipping industry in the southwestern United States, Mexico, Central America, and New Zealand. In the current study, we evaluated the knockdown effect of 12 insecticides against adult B. cockerelli, and we examined the effects of treating potato leaves: top side only, bottom side only, or both sides. Within 48 h of exposure, abamectin showed the highest and most consistent rate of adult B. cockerelli mortality and a dosage response to three dosages within labeled field rates. Choice tests conducted in petri dishes, involving untreated potato leaves and leaves treated with abamectin, revealed that abamectin did not affect host preference of adult B. cockerelli. A residual test under field conditions revealed that, although highly effective immediately after application, abamectin-effect was nonsignificantly different from control treatments 24 and 48 h after field application. Higher adult B. cockerelli mortality was recorded from potato plants treated with ground application compared with aerial 48 h after application. Our results indicated that abamectin has a high knockdown effect on adult B. cockerelli and that it can be used effectively in insecticide rotation programs against adult B. cockerelli and ZC control in potatoes.


Assuntos
Hemípteros/efeitos dos fármacos , Controle de Insetos/métodos , Insetos Vetores/efeitos dos fármacos , Inseticidas/toxicidade , Solanum tuberosum/microbiologia , Animais , Relação Dose-Resposta a Droga , Hemípteros/microbiologia , Hemípteros/fisiologia , Insetos Vetores/microbiologia , Insetos Vetores/fisiologia , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Mortalidade
17.
Diagn Cytopathol ; 37(4): 251-7, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19217031

RESUMO

Accurate assessment of estrogen receptor (ER), progesterone receptor (PR), and Her2 status of breast carcinomas is critical for predicting response to systemic therapies. Recently, developed rabbit monoclonal antibodies (RMab) are reported to have higher sensitivity than murine monoclonal antibodies (Mab). This study compares RMabs against FDA-approved Mab (FMab) in breast carcinoma cell block sections using visual and image quantification. Cell blocks from 52 breast cancers were studied. Immunohistochemistry using RMab (ER, PR, and Her2) was compared with FMabs (ER, PR, Dako) and HercepTest (HerFDA). Fluorescent in situ hybridization (FISH) was used as a reference standard for Her2. Slides were later scanned and reanalyzed with an automated cellular imaging system (ACIS III, Dako). Frequency of ER (38.5% vs. 36.5% for visual; 55.8% vs. 57.7% for image) and PR (28.8% vs. 36.5% for visual; 50% vs. 51.9% for image), and concordance (overall agreement is 71.2% and 75% for visual and image ER; and 84.6% and 59.6% for visual and image PR) were similar for both FMab and RMab, respectively. Overall agreement (53.8% vs. 77.1% for visual and image detection, respectively, using HerFDA and RMab) is poor to moderate for Her2. Visual Her2 (RMab) has the highest concordance (94.1%), and visual HerFDA has the lowest concordance (35.3%) with FISH. ER and PR analysis (FMab vs. RMab) are almost comparable using both detection methods with good overall agreement. For Her2 overexpression, RMab proved to be superior to HerFDA and showed excellent agreement with FISH results with both quantitative detection methods.


Assuntos
Anticorpos Monoclonais/imunologia , Neoplasias da Mama/metabolismo , Processamento de Imagem Assistida por Computador/métodos , Microscopia/métodos , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Receptor ErbB-2/imunologia , Receptores de Estrogênio/imunologia , Receptores de Progesterona/imunologia
18.
Nucleic Acids Res ; 37(Database issue): D690-7, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19033362

RESUMO

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases, and other information for chordate, selected model organism and disease vector genomes. As of release 51 (November 2008), Ensembl fully supports 45 species, and three additional species have preliminary support. New species in the past year include orangutan and six additional low coverage mammalian genomes. Major additions and improvements to Ensembl since our previous report include a major redesign of our website; generation of multiple genome alignments and ancestral sequences using the new Enredo-Pecan-Ortheus pipeline and development of our software infrastructure, particularly to support the Ensembl Genomes project (http://www.ensemblgenomes.org/).


Assuntos
Bases de Dados Genéticas , Genômica , Animais , Variação Genética , Humanos , Internet , Alinhamento de Sequência
19.
Infect Genet Evol ; 9(3): 308-13, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18262474

RESUMO

High-throughput genome sequencing techniques have now reached vector biology with an emphasis on those species that are vectors of human pathogens. The first mosquito to be sequenced was Anopheles gambiae, the vector for Plasmodium parasites that cause malaria. Further mosquitoes have followed: Aedes aegypti (yellow fever and dengue fever vector) and Culex pipiens (lymphatic filariasis and West Nile fever). Species that are currently in sequencing include the body louse Pediculus humanus (Typhus vector), the triatomine Rhodnius prolixus (Chagas disease vector) and the tick Ixodes scapularis (Lyme disease vector). The motivations for sequencing vector genomes are to further understand vector biology, with an eye on developing new control strategies (for example novel chemical attractants or repellents) or understanding the limitations of current strategies (for example the mechanism of insecticide resistance); to analyse the mechanisms driving their evolution; and to perform an exhaustive analysis of the gene repertory. The proliferation of genomic data creates the need for efficient and accessible storage. We present VectorBase, a genomic resource centre that is both involved in the annotation of vector genomes and act as a portal for access to the genomic information (http://www.vectorbase.org).


Assuntos
Vetores Artrópodes/genética , Patógenos Transmitidos pelo Sangue , Bases de Dados de Ácidos Nucleicos , Genômica , Animais , Evolução Molecular , Etiquetas de Sequências Expressas , Genoma de Inseto , Humanos , Filogenia , Análise de Sequência de DNA
20.
Br J Neurosurg ; 22(6): 793-7, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19085365

RESUMO

We report two patients with spinal epithelioid hemangioendothelioma (EH), an uncommon vascular, potentially malignant tumour. Neurological signs, diagnostic images, surgical techniques and complications, histology and the role of adjuvant therapy are discussed. Primary manifestation of EH of the vertebral column is rare. Thorough preoperative clinical and radiological workup, radical surgical excision, and close postoperative follow-up are recommended.


Assuntos
Vértebras Cervicais , Hemangioendotelioma Epitelioide , Neoplasias da Coluna Vertebral/diagnóstico , Adulto , Vértebras Cervicais/cirurgia , Diagnóstico Diferencial , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/cirurgia , Humanos , Hipestesia/etiologia , Masculino , Pessoa de Meia-Idade , Compressão da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Resultado do Tratamento
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