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2.
AJNR Am J Neuroradiol ; 41(12): 2235-2242, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33214184

RESUMO

BACKGROUND AND PURPOSE: Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast. MATERIALS AND METHODS: We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study. RESULTS: The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12-0.96; P = .04). CONCLUSIONS: Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.


Assuntos
Infarto Encefálico/diagnóstico por imagem , Meios de Contraste , Interpretação de Imagem Assistida por Computador , Compostos de Iodo , Neuroimagem/métodos , Software , Idoso , Idoso de 80 Anos ou mais , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Estudos Retrospectivos
3.
Rev Geophys ; 58(1): e2019RG000660, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32734279

RESUMO

Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6 W m-2, or -2.0 to -0.4 W m-2 with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds.

4.
AJNR Am J Neuroradiol ; 41(2): 268-273, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32001445

RESUMO

BACKGROUND AND PURPOSE: Arterial access is a technical consideration of mechanical thrombectomy that may affect procedural time, but few studies exist detailing the relationship of anatomy to procedural times and patient outcomes. We sought to investigate the respective impact of aortic arch and carotid artery anatomy on endovascular procedural times in patients with large-vessel occlusion. MATERIALS AND METHODS: We retrospectively reviewed imaging and medical records of 207 patients from 2 academic institutions who underwent mechanical thrombectomy for anterior circulation large-vessel occlusion from January 2015 to July 2018. Preintervention CTAs were assessed to measure features of the aortic arch and ipsilateral great vessel anatomy. These included the cranial-to-caudal distance from the origin of the innominate artery to the top of the aortic arch and the takeoff angle of the respective great vessel from the arch. mRS scores were calculated from rehabilitation and other outpatient documentation. We performed bootstrap, stepwise regressions to model groin puncture to reperfusion time and binary mRS outcomes (good outcome, mRS ≤ 2). RESULTS: From our linear regression for groin puncture to reperfusion time, we found a significant association of the great vessel takeoff angle (P = .002) and caudal distance from the origin of the innominate artery to the top of the aortic arch (P = .05). Regression analysis for the binary mRS revealed a significant association with groin puncture to reperfusion time (P < .001). CONCLUSIONS: These results demonstrate that patients with larger takeoff angles and extreme aortic arches have an association with longer procedural times as approached from transfemoral access routes.


Assuntos
Aorta Torácica/anatomia & histologia , Artéria Carótida Primitiva/anatomia & histologia , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/cirurgia , Isquemia Encefálica/cirurgia , Artéria Carótida Primitiva/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombectomia/métodos , Resultado do Tratamento
5.
AJNR Am J Neuroradiol ; 40(4): 737-744, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30923086

RESUMO

BACKGROUND AND PURPOSE: Our aim was to use 2D convolutional neural networks for automatic segmentation of the spinal cord and traumatic contusion injury from axial T2-weighted MR imaging in a cohort of patients with acute spinal cord injury. MATERIALS AND METHODS: Forty-seven patients who underwent 3T MR imaging within 24 hours of spinal cord injury were included. We developed an image-analysis pipeline integrating 2D convolutional neural networks for whole spinal cord and intramedullary spinal cord lesion segmentation. Linear mixed modeling was used to compare test segmentation results between our spinal cord injury convolutional neural network (Brain and Spinal Cord Injury Center segmentation) and current state-of-the-art methods. Volumes of segmented lesions were then used in a linear regression analysis to determine associations with motor scores. RESULTS: Compared with manual labeling, the average test set Dice coefficient for the Brain and Spinal Cord Injury Center segmentation model was 0.93 for spinal cord segmentation versus 0.80 for PropSeg and 0.90 for DeepSeg (both components of the Spinal Cord Toolbox). Linear mixed modeling showed a significant difference between Brain and Spinal Cord Injury Center segmentation compared with PropSeg (P < .001) and DeepSeg (P < .05). Brain and Spinal Cord Injury Center segmentation showed significantly better adaptability to damaged areas compared with PropSeg (P < .001) and DeepSeg (P < .02). The contusion injury volumes based on automated segmentation were significantly associated with motor scores at admission (P = .002) and discharge (P = .009). CONCLUSIONS: Brain and Spinal Cord Injury Center segmentation of the spinal cord compares favorably with available segmentation tools in a population with acute spinal cord injury. Volumes of injury derived from automated lesion segmentation with Brain and Spinal Cord Injury Center segmentation correlate with measures of motor impairment in the acute phase. Targeted convolutional neural network training in acute spinal cord injury enhances algorithm performance for this patient population and provides clinically relevant metrics of cord injury.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Transtornos Motores/etiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Contusões/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino
6.
AJNR Am J Neuroradiol ; 39(12): 2211-2217, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30467218

RESUMO

BACKGROUND AND PURPOSE: The aging HIV-infected (HIV+) population has increased vascular comorbidities, including stroke, and increased cognitive deficits compared with the general population. Arterial spin-labeling is a technique to measure cerebral blood flow and is more sensitive than regional volume loss in assessing neurodegenerative diseases and cognitive aging. Previous studies have found global cerebral perfusion abnormalities in the HIV+ participants. In this study, we evaluated the specific regional pattern of CBF abnormalities in older HIV+ participants using quantitative whole-brain arterial spin-labeling. MATERIALS AND METHODS: CBF data from the UCSF HIV Over 60 Cohort and the Alzheimer Disease Neuroimaging Initiative were retrospectively evaluated to identify 19 HIV+ older adults, all with plasma viral suppression (including 5 with HIV-associated neurocognitive disorder); 13 healthy, age-matched controls; and 19 participants with early mild cognitive impairment. CBF values were averaged by ROI and compared among the 3 groups using generalized linear models. RESULTS: When we accounted for age, education, sex, and vascular risk factors, the HIV+ participants demonstrated alterations in regional cerebral perfusion, including hypoperfusion of bilateral temporal, parietal, and occipital brain regions compared with both clinically healthy participants and those with mild cognitive impairment. Arterial spin-labeling showed reasonable test characteristics in distinguishing those with HIV-associated neurocognitive disorder from healthy controls and participants with mild cognitive impairment. CONCLUSIONS: This study found specific CBF patterns associated with HIV status despite viral suppression-data that should animate further investigations into the pathobiologic basis of vascular and cognitive abnormalities in HIV-associated neurocognitive disorders.


Assuntos
Complexo AIDS Demência/diagnóstico por imagem , Complexo AIDS Demência/fisiopatologia , Circulação Cerebrovascular/fisiologia , Neuroimagem/métodos , Idoso , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Marcadores de Spin
7.
J Clin Pharm Ther ; 43(6): 910-913, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29956355

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Candida catenulata is a fungus commonly found in Australian cheeses. C. catenulata has been identified as the causative pathogen for one report of onychomycosis and one report of candidaemia. CASE DESCRIPTION: A 37-year-old male underwent surgery for an incarcerated umbilical hernia repair and bowel obstruction and presented with severe abdominal pain and ascitic fluid draining from the surgical site. C. catenulata was isolated in blood cultures. The patient was treated with antifungal therapy for approximately 6 weeks. WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case describing successful treatment of possible fungal endocarditis caused by C. catenulata.


Assuntos
Antifúngicos/administração & dosagem , Candidemia/tratamento farmacológico , Endocardite/tratamento farmacológico , Fluconazol/administração & dosagem , Dor Abdominal/etiologia , Administração Oral , Adulto , Candida/isolamento & purificação , Candidemia/diagnóstico , Candidemia/microbiologia , Endocardite/diagnóstico , Endocardite/microbiologia , Fluconazol/uso terapêutico , Hérnia Umbilical/cirurgia , Humanos , Obstrução Intestinal/cirurgia , Cirrose Hepática/patologia , Masculino , Resultado do Tratamento
8.
Environ Geochem Health ; 40(1): 1-57, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27921191

RESUMO

The public health impact of hydraulic fracturing remains a high profile and controversial issue. While there has been a recent surge of published papers, it remains an under-researched area despite being possibly the most substantive change in energy production since the advent of the fossil fuel economy. We review the evidence of effects in five public health domains with a particular focus on the UK: exposure, health, socio-economic, climate change and seismicity. While the latter would seem not to be of significance for the UK, we conclude that serious gaps in our understanding of the other potential impacts persist together with some concerning signals in the literature and legitimate uncertainties derived from first principles. There is a fundamental requirement for high-quality epidemiological research incorporating real exposure measures, improved understanding of methane leakage throughout the process, and a rigorous analysis of the UK social and economic impacts. In the absence of such intelligence, we consider it prudent to incentivise further research and delay any proposed developments in the UK. Recognising the political realities of the planning and permitting process, we make a series of recommendations to protect public health in the event of hydraulic fracturing being approved in the UK.


Assuntos
Fraturamento Hidráulico , Gás Natural , Saúde Pública , Animais , Mudança Climática , Terremotos , Exposição Ambiental , Humanos , Fatores Socioeconômicos , Reino Unido
9.
AJNR Am J Neuroradiol ; 38(2): 410-417, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27979798

RESUMO

BACKGROUND AND PURPOSE: Recent advances in spinal cord imaging analysis have led to the development of a robust anatomic template and atlas incorporated into an open-source platform referred to as the Spinal Cord Toolbox. Using the Spinal Cord Toolbox, we sought to correlate measures of GM, WM, and cross-sectional area pathology on T2 MR imaging with motor disability in patients with acute flaccid myelitis. MATERIALS AND METHODS: Spinal cord imaging for 9 patients with acute flaccid myelitis was analyzed by using the Spinal Cord Toolbox. A semiautomated pipeline using the Spinal Cord Toolbox measured lesion involvement in GM, WM, and total spinal cord cross-sectional area. Proportions of GM, WM, and cross-sectional area affected by T2 hyperintensity were calculated across 3 ROIs: 1) center axial section of lesion; 2) full lesion segment; and 3) full cord atlas volume. Spearman rank order correlation was calculated to compare MR metrics with clinical measures of disability. RESULTS: Proportion of GM metrics at the center axial section significantly correlated with measures of motor impairment upon admission (r [9] = -0.78; P = .014) and at 3-month follow-up (r [9] = -0.66; P = .05). Further, proportion of GM extracted across the full lesion segment significantly correlated with initial motor impairment (r [9] = -0.74, P = .024). No significant correlation was found for proportion of WM or proportion of cross-sectional area with clinical disability. CONCLUSIONS: Atlas-based measures of proportion of GM T2 signal abnormality measured on a single axial MR imaging section and across the full lesion segment correlate with motor impairment and outcome in patients with acute flaccid myelitis. This is the first atlas-based study to correlate clinical outcomes with segmented measures of T2 signal abnormality in the spinal cord.


Assuntos
Mielite/diagnóstico por imagem , Mielite/terapia , Traumatismos da Medula Espinal/diagnóstico por imagem , Adulto , Anatomia Transversal , Atlas como Assunto , Criança , Pré-Escolar , Avaliação da Deficiência , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Mielite/etiologia , Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/complicações , Resultado do Tratamento , Adulto Jovem
10.
Psychol Med ; 47(4): 680-689, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27834159

RESUMO

BACKGROUND: Previous findings have been mixed regarding the relationship between maternal depressive symptoms and child cognitive development. The objective of this study was to systematically review relevant literature and to perform a meta-analysis. METHOD: Three electronic databases (PubMed, EMBASE, PsycINFO) were searched. Initial screening was conducted independently by two reviewers. Studies selected for detailed review were read in full and included based on a set of criteria. Data from selected studies were abstracted onto a standardized form. Meta-analysis using the inverse variance approach and random-effects models was conducted. RESULTS: The univariate analysis of 14 studies revealed that maternal depressive symptoms are related to lower cognitive scores among children aged ⩽56 months (Cohen's d = -0.25, 95% CI -0.39 to -0.12). The synthesis of studies controlling for confounding variables showed that the mean cognitive score for children 6-8 weeks post-partum whose mothers had high depressive symptoms during the first few weeks postpartum was approximately 4.2 units lower on the Mental Developmental Index (MDI) of the Bayley Scales of Infant and Toddler Development (BSID) compared with children with non-symptomatic mothers (B̂ = -4.17, 95% CI -8.01 to -0.32). CONCLUSIONS: The results indicated that maternal depressive symptoms are related to lower cognitive scores in early infancy, after adjusting for confounding factors. An integrated approach for supporting child cognitive development may include program efforts that promote maternal mental health in addition to family economic wellbeing, responsive caregiving, and child nutrition.


Assuntos
Desenvolvimento Infantil/fisiologia , Filho de Pais com Deficiência , Cognição/fisiologia , Depressão Pós-Parto , Transtorno Depressivo Maior , Pré-Escolar , Feminino , Humanos , Lactente
11.
J Dairy Sci ; 94(3): 1605-15, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21338828

RESUMO

Reducing the sodium content in cheese is expected to contribute to reducing the overall intake of sodium by US consumers. The purpose of this study was to measure the sodium levels in cheeses that are most commonly purchased by US consumers in the retail market, including brand and private label. A secondary purpose of the study was to generate data that can enable the dairy industry to adopt best practices regarding sodium levels in cheeses. The sodium content of a total of 1,665 samples of Cheddar (650 samples), low moisture part skim (LMPS) Mozzarella (746 samples), and process cheese singles (269 samples) from 4 geographical regions were collected over a period of 3 wk, and were analyzed over a 1-mo period. Process cheese contained the highest mean level of sodium (1,242 mg/100g), followed by string cheese (724 mg/100g). Across Cheddar cheese forms and brands, the mean analytical sodium was 615 mg/100g, with 95% between 474 and 731 mg/100g; label sodium ranged from 600 to 800 mg/100g (mean 648 mg). Across all LMPS Mozzarella forms and brands, the mean analytical sodium was 666 mg/100g, with 95% between 452 and 876 mg/100g; label sodium ranged from 526 to 89 3mg/100g (mean 685 mg). Across all process cheese forms and brands, the mean analytical sodium was 1,242 mg/100g, with 95% between 936 and 1,590 mg/100g; label sodium ranged from 1,185 to 1,740 mg/100g (mean 1,313 mg/100g). These findings demonstrate that manufacturers tended to be conservative with their reporting of sodium on labels. Manufacturers need to reduce variability to better target desired sodium levels, which is an opportunity for better process control, and will enable them to label sodium more accurately.


Assuntos
Queijo/análise , Sódio na Dieta/análise , Animais , Rotulagem de Alimentos , Estados Unidos
12.
Transpl Infect Dis ; 13(2): 117-21, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20804534

RESUMO

A total of 26 adults with hematologic malignancies and/or hematopoietic stem cell transplant were treated for respiratory syncytial virus (RSV) infection based on an institutional guideline. Thirteen patients received aerosolized ribavirin, and 13 received aerosolized ribavirin and intravenous palivizumab. Two deaths, not attributed to RSV infection, occurred within 90 days of diagnosis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/etiologia , Ribavirina/uso terapêutico , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Palivizumab , Ribavirina/administração & dosagem
14.
Int Health ; 2(3): 228, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24037704

RESUMO

The Publisher regrets that an error occurred in the name of the 6th listed co-author for this paper. B. Matthias was listed in the original paper instead of M. Borchert; the correct listing can be seen above.

15.
J R Soc Med ; 102(1): 22-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19147853

RESUMO

OBJECTIVES: The Community Care (Delayed Discharges, etc.) Act, 2003 was aimed at reducing the number of patients whose discharge from hospital was delayed, incorporating financial incentives based on a model from Sweden. The Act permitted NHS hospital trusts to charge local authority Social Service Departments for delays they were deemed responsible for and was accompanied by grants aimed at supporting improvements in the transfer of care. This study aims to assess how far the subsequent reduction in delays has been due to the operation of the Act, and to evaluate the extent that the legislation increased efficiency across health and social care. DESIGN: Analysis and interpretation of a range of official routine health statistics plus unpublished performance data. Setting Data on patients delayed in hospital in England from 2001-2002 to 2006-2007 and trends in hospital activity. MAIN OUTCOME MEASURES: Trend analysis of health statistics and performance data relating to delayed discharges and other relevant indicators. Results Although there has been an overall reduction in delayed discharges, this trend predates the implementation of the Act. Overall, bed- days lost to delayed discharges accounted for only a small proportion of all bed-days - 1.6% in 2006-2007, and over the period studied the causes of the majority of delays were attributed to the NHS (68%). CONCLUSIONS: These findings indicate little evidence to support the policy of charging social services to improve public sector efficiency. The focus on reducing delays should be set in the context of the wider health economy. There are a number of pressures to reduce the time patients spend in hospital including fewer beds and increasing numbers of admissions, plus a rise in emergency readmission rates is noted. There are few good data available to monitor the impact of earlier discharge, such as on the quality and availability of post-discharge care.


Assuntos
Política de Saúde/tendências , Alta do Paciente/tendências , Medicina Estatal/tendências , Ocupação de Leitos/tendências , Tempo de Internação/tendências , Alta do Paciente/estatística & dados numéricos , Medicina Estatal/organização & administração , Reino Unido
16.
J Public Health (Oxf) ; 29(3): 281-7, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17650527

RESUMO

BACKGROUND: The belief that many delays in discharge from hospital were caused by social service departments (SSDs) led to the Community Care Act 2003 giving NHS hospitals in England the power to charge SSDs. METHODS: We surveyed 150 SSDs in England about the implementation of the Act and used routine data to analyse trends in the number of delayed discharge patients; the number and cause of delayed discharge bed days by sector; and the proportion of inpatient bed days that consisted of delayed discharges. FINDINGS: Most hospitals opted not to charge SSDs for delays. Almost two thirds of SSDs (62%) made no payment of any kind to an acute hospital in 2004/05 and 2005/06, preferring to work collaboratively. The fall in number of 'delayed discharge patients' is a long term trend which precedes the implementation of the 2003 Act. Delayed discharge bed days accounted for 1.58% of all inpatient bed days in 2004/05. Contrary to popular opinion, the NHS accounted for two thirds (67%) of bed day delays, lack of suitable alternative NHS provision and services is a key factor. Patients are being discharged in greater numbers and earlier in their post-acute recovery phase. There are however questions about the quality and safety of early discharge. For example, emergency hospital readmissions rates have risen from 5.4% in 2002/03 to 6.7% in 2005/06, and patient dissatisfaction is significant. CONCLUSION: Although delays in discharge from acute hospital beds have fallen, the quality of discharge and the capacity of Primary Care Trusts (PCTs) and SSDs to ensure appropriate and adequate post-discharge care is not as it should be. Contrary to popular perception, social services delays are of less significance than delays attributable to the NHS. There is no evidence to support government policy of charging SSDs for delay. Other factors, including NHS provision, are important, and a comprehensive overview of health and social care is vital.


Assuntos
Serviços de Saúde Comunitária/legislação & jurisprudência , Honorários e Preços/legislação & jurisprudência , Administração Financeira de Hospitais , Hospitais Públicos/legislação & jurisprudência , Alta do Paciente/economia , Serviço Social/economia , Assistência ao Convalescente/legislação & jurisprudência , Ocupação de Leitos/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Hospitais Públicos/economia , Humanos , Alta do Paciente/legislação & jurisprudência , Indicadores de Qualidade em Assistência à Saúde , Serviço Social/normas , Medicina Estatal , Inquéritos e Questionários , Fatores de Tempo , Reino Unido
17.
Gene Ther ; 13(12): 974-85, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16511521

RESUMO

Surfactant deficiency is an important contributor to the acute respiratory distress syndrome, a disorder that commonly occurs after bacterial sepsis. CTP:phosphocholine cytidylyltransferase (CCTalpha) is the rate-limiting enzyme required for the biosynthesis of dipalmitoylphosphatidylcholine (DPPC), the major phospholipid of surfactant. In this study, a cDNA encoding a novel, calpain-resistant mutant CCTalpha enzyme was delivered intratracheally in mice using a replication-deficient adenovirus 5 CTP:phosphocholine cytidylyltransferase construct (Ad5-CCT(Penta)) in models of bacterial sepsis. Ad5-CCT(Penta) gene transfer produced high-level CCTalpha gene expression, increased alveolar surfactant (DPPC) levels and improved lung surface tension and pressure-volume relationships relative to control mice. Pseudomonas aeruginosa (PA103) decreased DPPC synthesis, in part, via calpain-mediated degradation of CCTalpha. Deleterious effects of Pseudomonas on surfactant were lessened after infection with a mutant strain lacking the type III exotoxin, Exo U. Replication-deficient adenovirus 5 CTP:phosphocholine cytidylyltransferase gene delivery improved lung biophysical properties by optimizing surface activity in this Pseudomonas model of proteinase-mediated lung injury. The studies are the first demonstration of in vivo gene transfer of a lipogenic enzyme resulting in improved lung mechanics. The studies suggest that augmentation of DPPC synthesis via gene delivery of CCTalpha can attenuate impaired lung function in surfactant-deficient states such as bacterial sepsis.


Assuntos
Colina-Fosfato Citidililtransferase/genética , Terapia Genética/métodos , Pneumopatias/terapia , Infecções por Pseudomonas/terapia , Surfactantes Pulmonares/administração & dosagem , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Doença Aguda , Adenoviridae/genética , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Colina-Fosfato Citidililtransferase/administração & dosagem , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Pulmão/enzimologia , Pneumopatias/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infecções por Pseudomonas/enzimologia , Transdução Genética/métodos
18.
Eur J Anaesthesiol ; 22(9): 717-22, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16163920

RESUMO

BACKGROUND AND OBJECTIVE: Hypotension, the commonest side-effect of spinal anaesthesia, results from sympathetic denervation. This study compared patient positioning (supine vs. decubitus) on haemodynamic variables during spinal anaesthesia. METHODS: After intravenous crystalloid preloading with 5 mL kg(-1), hyperbaric bupivacaine 0.5% 2.5 mL was injected intrathecally at the L2-3 or L3-4 interspace. Patients were then randomly assigned to be positioned immediately supine and horizontal for 30 min (Group SUP, n = 12), or remained in the lateral decubitus position (fractured hip dependent) for 30 min (Group LAT, n = 14). Systolic blood pressure, mean arterial pressure, and loss of sensation of pinprick sensation were recorded prior to induction of spinal anaesthesia (baseline) and at 1, 2, 3, 5, 10, 15, 30, 45, 60, 90 and 120 min after intrathecal injection. RESULTS: In Group SUP, the percent maximum systolic blood pressure (36 +/- 13%) and percent maximum mean arterial pressure decreases (27 +/- 13%) were significantly greater (P < 0.05) than in Group LAT (30 +/- 8% and 23 +/- 11%, respectively). Additionally, there was a borderline significant delay in the time to maximum systolic blood pressure decrease in Group LAT (38 +/- 30 min) when compared with Group SUP (20 +/- 17 min, P = 0.06), while the total dose of ephedrine required in the SUP group (30 mg) was greater than that required in the LAT group (15 mg, P = 0.05). In Group LAT patients, the mean level of denervation on the operative side extended 2 dermatomes more cephalad than in Group SUP. CONCLUSIONS: Lateral positioning for spinal anaesthesia delays the onset of hypotension, while requiring smaller total doses of vasoconstrictors for blood pressure maintenance.


Assuntos
Raquianestesia/métodos , Anestésicos Locais/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Bupivacaína/administração & dosagem , Postura/fisiologia , Decúbito Dorsal/fisiologia , Idoso , Idoso de 80 Anos ou mais , Efedrina/administração & dosagem , Feminino , Fraturas do Colo Femoral/cirurgia , Humanos , Hipotensão/prevenção & controle , Injeções Espinhais , Masculino , Bloqueio Nervoso , Sensação/efeitos dos fármacos , Simpatomiméticos/administração & dosagem , Fatores de Tempo , Vasoconstritores/administração & dosagem
19.
Dev Dyn ; 226(3): 439-45, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12619130

RESUMO

Replication-defective retroviral vectors are efficient vehicles for the delivery of exogenous genes, and they may be used in the generation of transgenic animals. The replication-defective retroviral SNTZ vector carrying the lacZ gene with a nuclear localized signal was injected into the subgerminal cavity of freshly laid eggs. Subsequently, the eggs were allowed to hatch, and the chickens were screened for the lacZ gene by using the polymerase chain reaction. Eight of 15 male chickens that survived to sexual maturity contained the lacZ gene in their semen. Subsequently, these males were mated with wild-type female chickens. From one of the eight lacZ-positive G(0) males, two lacZ-positive male chickens were produced from a total of 224 G(1) progeny for a germline transmission rate of 0.89%. Both G(1) male chickens carrying the lacZ gene were mated with wild-type female chickens and 46.5% of the G(2) progeny contained the lacZ gene, which is consistent with the expected Mendelian 50% ratio for a heterozygous dominant allele. The product of the lacZ gene, nuclear localized beta-galactosidase, was expressed in primary myoblast cultures derived from G(2) chickens, and it was also expressed in whole G(2) chicken embryos.


Assuntos
Animais Geneticamente Modificados , Galinhas , Óperon Lac , beta-Galactosidase/genética , Animais , Embrião de Galinha , Feminino , Expressão Gênica , Técnicas de Transferência de Genes , Masculino , Retroviridae/genética
20.
Poult Sci ; 81(11): 1703-8, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12455598

RESUMO

Myofiber growth is dependent upon the contribution of new nuclei from the mitotically active satellite cell population. The objective of this study was to examine satellite cell mitotic activity in conjunction with different nutritional paradigms during the early posthatch period. Turkey poults were provided a standard turkey starter diet; the starter diet top-dressed with a hydrated low-fat, highly digestible protein and carbohydrate nutritional hatchling supplement, Oasis; the starter diet top-dressed with Solka-floc dyed green; or no food for the first 3 d posthatch. All birds were fed a standard starter diet during the experimental period. 5-Bromo-2'-deoxyuridine (BrdU) was continuously infused into all treatments (n = 5 all groups) between hatch and 3 d of age. A second group of identically treated poults housed in separate pens (n = 3 to 5) was continuously infused with BrdU between 2 and 9 d of age. Mitotically active satellite cells were identified in the pectoralis thoracicus and quantitated using BrdU immunohistochemistry in combination with computer-based image analysis. Satellite cell mitotic activity was significantly higher (P < or = 0.05) in the birds fed a standard starter diet compared to all other treatments at 3 d posthatch. However, there were no (P > or = 0.05) differences in satellite cell mitotic activity among treatments at 9 d posthatch. The results of the current study suggest that any improvements in meat yield through early nutritional supplementation do not appear to occur through a satellite cell pathway and that there is no compensatory response in the satellite cell population following refeeding after early posthatch starvation.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Mitose/fisiologia , Músculos Peitorais/citologia , Células Satélites de Músculo Esquelético/citologia , Perus/crescimento & desenvolvimento , Fatores Etários , Animais , Antimetabólitos , Bromodesoxiuridina , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica/veterinária , Músculos Peitorais/crescimento & desenvolvimento , Músculos Peitorais/metabolismo , Distribuição Aleatória
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