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1.
Basic Res Cardiol ; 117(1): 25, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488105

RESUMO

Cardiac action potential (AP) shape and propagation are regulated by several key dynamic factors such as ion channel recovery and intracellular Ca2+ cycling. Experimental methods for manipulating AP electrical dynamics commonly use ion channel inhibitors that lack spatial and temporal specificity. In this work, we propose an approach based on optogenetics to manipulate cardiac electrical activity employing a light-modulated depolarizing current with intensities that are too low to elicit APs (sub-threshold illumination), but are sufficient to fine-tune AP electrical dynamics. We investigated the effects of sub-threshold illumination in isolated cardiomyocytes and whole hearts by using transgenic mice constitutively expressing a light-gated ion channel (channelrhodopsin-2, ChR2). We find that ChR2-mediated depolarizing current prolongs APs and reduces conduction velocity (CV) in a space-selective and reversible manner. Sub-threshold manipulation also affects the dynamics of cardiac electrical activity, increasing the magnitude of cardiac alternans. We used an optical system that uses real-time feedback control to generate re-entrant circuits with user-defined cycle lengths to explore the role of cardiac alternans in spontaneous termination of ventricular tachycardias (VTs). We demonstrate that VT stability significantly decreases during sub-threshold illumination primarily due to an increase in the amplitude of electrical oscillations, which implies that cardiac alternans may be beneficial in the context of self-termination of VT.


Assuntos
Optogenética , Taquicardia Ventricular , Potenciais de Ação/fisiologia , Animais , Iluminação , Camundongos , Miócitos Cardíacos/fisiologia , Optogenética/métodos
2.
Allergy ; 70(3): 275-84, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25477068

RESUMO

BACKGROUND: We have shown that mycobacterial antigens and CpG oligodeoxynucleotides downmodulate airway allergic inflammation by mechanisms dependent on T-cell activation. Here, we investigated the participation of the innate response, particularly the role of MyD88 adaptor, and Fas molecules in the effectiveness of DNA-HSP65 or CpG/culture filtrated proteins (CFP) immunotherapy. METHODS: Mice sensitized and challenged with Der p 1 allergen were treated with DNA-HSP65, CpG/CFP, or with adoptively transferred cells from immunized mice. The treatment efficacy was assessed by evaluating eosinophil recruitment, antibody, and cytokine production. RESULTS: In addition to downregulating the Th2 response, DNA-HSP65 and CpG/CFP promoted IL-10 and IFN-γ production. Adoptive transfer of cells from mice immunized with DNA-HSP65 or CpG/CFP to allergic recipients downmodulated the allergic response. Notably, transfer of cells from DNA-HSP65- or CpG/CFP-immunized MyD88(-/-) mice failed to reduce allergy. Additionally, for effective reduction of allergy by cells from CpG/CFP-immunized mice, Fas molecules were required. Although DNA-HSP65 or CpG/CFP immunization stimulated antigen-specific production of IFN-γ and IL-10, the effect of DNA-HSP65 was associated with IL-10 while CpG/CFP was associated with IFN-γ. Moreover, after stimulation with mycobacterial antigens plus Der p 1 allergen, cells from mite-allergic patients with asthma exhibited similar patterns of cytokine production as those found in the lung of treated mice. CONCLUSIONS: This study provides new insights on the mechanisms of allergen-free immunotherapy by showing that both DNA-HSP65 and CpG/CFP downregulated house dust mite-induced allergic airway inflammation via distinct pathways that involve not only induction of mycobacterial-specific adaptive responses but also signaling via MyD88 and Fas molecules.


Assuntos
Hipersensibilidade/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais , Receptor fas/metabolismo , Alérgenos/imunologia , Animais , Antígenos de Bactérias/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/genética , Asma/imunologia , Asma/metabolismo , Asma/terapia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Cisteína Endopeptidases/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/imunologia , Feminino , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Hipersensibilidade/terapia , Imunoterapia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Knockout , Mycobacterium/imunologia , Fator 88 de Diferenciação Mieloide/genética , Oligodesoxirribonucleotídeos/administração & dosagem , Pyroglyphidae/imunologia , Baço/citologia , Baço/imunologia , Baço/metabolismo , Receptor fas/genética
3.
J Intern Med ; 275(1): 49-58, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23962000

RESUMO

OBJECTIVES: Atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. Regulatory T cells (Tregs) and IL-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. We have previously shown that Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) decreases lung and colon inflammation by recruiting IL-10-producing Tregs. Therefore, the aim of this study was to investigate the effect of EFD BCG on the development of atherosclerosis. DESIGN: We used two strains of atherosclerosis-prone mice: Ldlr(-/-) (four or six EFD BCG injections) and Apoe(-/-) (six injections). RESULTS: In both models, EFD BCG significantly reduced the size of atherosclerotic lesions, increased IL-10 production and reduced the serum levels of pro-inflammatory cytokines (IL-6, IL-13, KC and tumour necrosis factor-α). Shortly after treatment with EFD BCG, the number of plasmacytoid dendritic cells (pDCs) and Foxp3(+) Tregs in the draining lymph nodes increased. EFD BCG also led to accumulation of Tregs, but not of pDCs in the spleen, and reduced activity of NF-κB and increased activity of PPAR-γ in both the spleen and vascular tissue of treated mice. CONCLUSION: EFD BCG has atheroprotective effects through IL-10 production and Treg expansion. These findings support a novel approach to the prevention and treatment of atherosclerosis.


Assuntos
Aterosclerose , Vacina BCG/farmacologia , Interleucina-10/metabolismo , Mycobacterium bovis/imunologia , Linfócitos T Reguladores , Animais , Aterosclerose/imunologia , Aterosclerose/prevenção & controle , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Liofilização/métodos , Fenômenos do Sistema Imunitário/efeitos dos fármacos , Camundongos , PPAR gama/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
4.
Ann Nutr Metab ; 59(2-4): 107-16, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22142767

RESUMO

BACKGROUND: trans unsaturated fatty acids are thought to interfere with essential fatty acid metabolism. To extend our knowledge of this phenomenon, we investigated the relationship between trans isomeric and long-chain polyunsaturated fatty acids (LCPUFA) in mothers during pregnancy and in their infants at birth. METHODS: Fatty acid composition of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined in Spanish (n = 120), German (n = 78) and Hungarian (n = 43) women at the 20th and 30th week of gestation, at delivery and in their newborns. RESULTS: At the 20th week of gestation, the sum of trans fatty acids in PE was significantly (p < 0.01) lower in Hungarian [0.73 (0.51), % wt/wt, median (IQR)] than in Spanish [1.42 (1.36)] and German [1.30 (1.21)] women. Docosahexaenoic acid (DHA) values in PE were significantly (p < 0.01) higher in Hungarian [5.65 (2.09)] than in Spanish [4.37 (2.60)] or German [4.39 (3.3.2)] women. The sum of trans fatty acids significantly inversely correlated to DHA in PCs in Spanish (r = -0.37, p < 0.001), German (n = -0.77, p < 0.001) and Hungarian (r = -0.35, p < 0.05) women, and in PEs in Spanish (r = -0.67, p < 0.001) and German (r = -0.71, p < 0.001), but not in Hungarian (r = -0.02) women. Significant inverse correlations were seen between trans fatty acids and DHA in PEs at the 30th week of gestation (n = 241, r = -0.52, p < 0.001), at delivery (n = 241, r = -0.40, p < 0.001) and in cord lipids (n = 218, r = -0.28, p < 0.001). CONCLUSION: Because humans cannot synthesize trans isomeric fatty acids, the data obtained in the present study support the concept that high maternal trans isomeric fatty acid intake may interfere with the availability of LCPUFA both for the mother and the fetus.


Assuntos
Ácido Araquidônico/sangue , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos Essenciais/sangue , Ácidos Graxos trans/sangue , Ácido Araquidônico/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Método Duplo-Cego , Eritrócitos/química , Ácidos Graxos Essenciais/administração & dosagem , Feminino , Alemanha , Idade Gestacional , Humanos , Hungria , Recém-Nascido , Isomerismo , Fenômenos Fisiológicos da Nutrição Materna , Fosfatidilcolinas/análise , Fosfatidiletanolaminas/análise , Gravidez , Espanha , Ácidos Graxos trans/administração & dosagem
5.
Commun Agric Appl Biol Sci ; 76(4): 667-70, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22702186

RESUMO

A network of Burkard 7-day spore-recording traps was set up in the Walloon Region in Belgium to monitor the airborne inoculum of wheat pathogens. The relationship between the airborne inoculum of Puccinia striiformis f.sp. tritici, the causal agent of stripe rust, and the disease incidence on plants in untreated plots located near each spore traps was studied during the 2008-2009 season. The presence of airborne inoculum was tested in four locations on tapes collected from the Burkard spore traps from 1 April to 14 June 2009. Total DNA from each fragment of spore trap tape corresponding to 1 day sampling was extracted. P. striiformis f.sp. tritici was quantified by real-time polymerase chain reaction (PCR) assay using specific primers and SYBRGreen. The airborne inoculum of P. striiformis was first detected between 7 and 13 April 2009, depending on the location in the Walloon Region. The first symptoms of stripe rust were observed in the fields between 15 May and 2 June 2009. The onset of the disease symptoms was always preceded by a higher peak of airborne inoculum about 15 days earlier. When P. striiformis f.sp. tritici was detected, the daily quantities of spores, collected from a volume of air of 14.4 m3, fluctuated between 0.23 and 154.66. This study shows that spore traps coupled with real-time PCR could be used to assess the airborne inoculum of P. striiformis in order to understand and predict stripe rust outbreaks.


Assuntos
Basidiomycota/fisiologia , Doenças das Plantas/prevenção & controle , Esporos Fúngicos/fisiologia , Triticum/microbiologia , Microbiologia do Ar , DNA Fúngico/genética , Monitoramento Ambiental , Doenças das Plantas/microbiologia
6.
Commun Agric Appl Biol Sci ; 75(4): 635-9, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21534470

RESUMO

A network of 10 Burkard 7-day spore-recording traps was set up in the Walloon region in Belgium to monitor the airborne inoculum of wheat pathogens. Three spore traps were used to analyse the distribution of Mycosphaerella graminicola inoculum at the field scale, at 1 m above ground level. Two traps were set up in a wheat field 100 m apart. The third trap was placed 70 m away in a sugar beet field adjacent to the wheat field. Total DNA from each fragment of spore trap tape corresponding to 1 day sampling was extracted and the quantity of M. graminicola was assessed using real-time polymerase chain reaction (PCR) assay. The experiment was conducted from July to October 2009. Positive detections were obtained for between 33 and 36 days, depending on the spore traps. When detected, the daily quantities of cDNA, collected from a volume of 14.4 m3, fluctuated between 4.84E+00 and 6.10E+03. Correlation coefficients higher than 0,82 and no significant differences were observed between the quantities of M. graminicola collected by the three spore traps, indicating that, at 1 m above ground level, the distribution of inoculum can be considered as homogenous at the tested field scale. This study confirms that spore traps coupled with real-time PCR could be used to assess the airborne inoculum of M. graminicola and to understand the development of the disease at this scale.


Assuntos
Microbiologia do Ar , Ascomicetos/isolamento & purificação , Triticum/microbiologia , Ascomicetos/genética
7.
Science ; 282(5389): 759-62, 1998 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-9784137

RESUMO

The virulence of the mycobacteria that cause tuberculosis depends on their ability to multiply in mammalian hosts. Disruption of the bacterial erp gene, which encodes the exported repetitive protein, impaired multiplication of M. tuberculosis and M. bovis Bacille Calmette-Guérin in cultured macrophages and mice. Reintroduction of erp into the mutants restored their ability to multiply. These results indicate that erp contributes to the virulence of M. tuberculosis.


Assuntos
Proteínas de Bactérias/fisiologia , Proteínas de Membrana/fisiologia , Mycobacterium tuberculosis/patogenicidade , Animais , Vacina BCG , Proteínas de Bactérias/análise , Proteínas de Bactérias/genética , Linhagem Celular , Genes Bacterianos , Teste de Complementação Genética , Imuno-Histoquímica , Pulmão/microbiologia , Macrófagos/microbiologia , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Mycobacterium bovis/genética , Mycobacterium bovis/crescimento & desenvolvimento , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/metabolismo , Fagossomos/microbiologia , Proteínas Recombinantes de Fusão , Tuberculose/microbiologia , Vacinas Atenuadas , Virulência/genética
8.
Eur Radiol ; 19(11): 2663-71, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19504109

RESUMO

We aimed to examine different intratumoral changes after single-dose and fractionated radiotherapy, using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in a rat rhabdomyosarcoma model. Four WAG/Rij rats with rhabdomyosarcomas in the flanks received single-dose radiotherapy of 8 Gy, and four others underwent fractionated radiotherapy (five times 3 Gy). In rats receiving single-dose radiotherapy, a significant perfusion decrease was found in the first 2 days post-treatment, with slow recuperation afterwards. No substantial diffusion changes could be seen; tumor growth delay was 12 days. The rats undergoing fractionated radiotherapy showed a similar perfusion decrease early after the treatment. However, a very strong increase in apparent diffusion coefficient occurred in the first 10 days; growth delay was 18 days. DW-MRI and DCE-MRI can be used to show early tumoral changes induced by radiotherapy. Single-dose and fractionated radiotherapy induce an immediate perfusion effect, while the latter induces more intratumoral necrosis.


Assuntos
Meios de Contraste/farmacologia , Imagem de Difusão por Ressonância Magnética/métodos , Fracionamento da Dose de Radiação , Radioterapia/métodos , Rabdomiossarcoma/radioterapia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Necrose , Transplante de Neoplasias , Perfusão , Ratos , Rabdomiossarcoma/patologia
9.
Acta Radiol ; 50(3): 276-87, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19160078

RESUMO

BACKGROUND: Rat model of reperfused partial liver infarction (RPLI) has been increasingly used in studying new diagnostics and therapeutics. PURPOSE: To characterize the RPLI model using magnetic resonance imaging (MRI), microangiography, and histopathology. MATERIAL AND METHODS: RPLI was induced in eight rats by occluding hepatic inflow to the right liver lobe for 3 hours. MRI was performed at a 1.5 T clinical scanner 6 hours after reperfusion to obtain T2-weighted (T2WI), T1-weighted (T1WI), contrast-enhanced (CE) T1WI, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps, T1-weighted dynamic contrast-enhanced (T1-DC) perfusion-weighted imaging (PWI), and T2*-weighted dynamic susceptibility contrast-enhanced (T2*-DSC) PWI images. Rats were sacrificed for microangiography and histomorphology. In vivo morphological and functional MRI parameters, including maximum initial slope (MIS), K value, relative blood flow (rBF), relative blood volume (rBV), time to peak (TTP), and mean transit time (MTT), were matched with postmortem findings. RESULTS: The infarcted lobe was conspicuous from normal liver with lower and higher signal intensity on T1WI (P=0.018) and T2WI (P=0.001), respectively. Contrast between infarcted and normal liver reversed on CE-T1WI after gadolinium injection. The infarction averaged 37.5% of total liver volume. DWI and ADC maps were able to detect subtle perfusion-related differences (P<0.05). With T1-DC-PWI, increased extravasation and vascular permeability were reflected by significantly greater MIS (P=0.034) and K value (P=0.014) in infarction. T2*-DSC-PWI showed lower rBF and rBV with shorter TTP and MTT in infarcted liver (P<0.05). In vivo MRI findings corresponded well with postmortem outcomes. CONCLUSION: RPLI in rats could be characterized by multiparametric MRI and postmortem assessments, with insight into the no-reflow phenomenon, which implies its further application for preclinical assessments of new pharmaceutics.


Assuntos
Angiografia Digital/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Modelos Animais de Doenças , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Infarto/diagnóstico , Fígado/irrigação sanguínea , Imageamento por Ressonância Magnética/métodos , Traumatismo por Reperfusão/diagnóstico , Animais , Meios de Contraste/administração & dosagem , Gadolínio DTPA , Infarto/patologia , Fenômeno de não Refluxo/diagnóstico , Fenômeno de não Refluxo/patologia , Curva ROC , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Sensibilidade e Especificidade
10.
Neuron ; 24(4): 929-40, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10624956

RESUMO

We used functional magnetic resonance imaging (fMRI) to investigate brain regions involved in extracting three-dimensional structure from motion. A factorial design included two-dimensional and three-dimensional structures undergoing rigid and nonrigid motions. As predicted from monkey data, the human homolog of MT/V5 was significantly more active when subjects viewed three-dimensional (as opposed to two-dimensional) displays, irrespective of their rigidity. Human MT/V5+ (hMT/V5+) is part of a network with right hemisphere dominance involved in extracting depth from motion, including a lateral occipital region, five sites along the intraparietal sulcus (IPS), and two ventral occipital regions. Control experiments confirmed that this pattern of activation is most strongly correlated with perceived three-dimensional structure, in as much as it arises from motion and cannot be attributed to numerous two-dimensional image properties or to saliency.


Assuntos
Percepção de Profundidade/fisiologia , Percepção de Movimento/fisiologia , Córtex Visual/fisiologia , Adolescente , Adulto , Mapeamento Encefálico , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Estimulação Luminosa , Rotação , Percepção de Tamanho/fisiologia
11.
Rheumatology (Oxford) ; 47(8): 1179-84, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18515868

RESUMO

OBJECTIVE: GCA carries an increased risk of developing thoracic aortic aneurysms. Previous work with fluorodeoxyglucose (FDG)-PET has shown that the aorta is frequently involved in this type of vasculitis. We wanted to investigate whether there is a correlation between the extent of vascular FDG uptake during the acute phase of GCA and the aortic diameter at late follow-up. METHODS: All patients with biopsy-proven GCA who ever underwent an FDG-PET scan in our centre were asked to undergo a CT scan of the aorta. The diameter of the aorta was measured at six different levels (ascending aorta, aortic arch, descending aorta, abdominal suprarenal, juxtarenal and infrarenal aorta) and the volumes of the thoracic and of the abdominal aorta were calculated. RESULTS: Forty-six patients agreed to participate (32 females, 14 males). A mean of 46.7 +/- 29.9 months elapsed between diagnosis and CT scan. All aortic dimensions were significantly smaller in women than in men, except for the diameter of the ascending aorta. Patients who had an increased FDG uptake in the aorta at diagnosis of GCA, had a significantly larger diameter of the ascending aorta (P = 0.025) and descending aorta (P = 0.044) and a significantly larger volume of the thoracic aorta (P = 0.029). In multivariate analysis, FDG uptake at the thoracic aorta was associated with late volume of the thoracic aorta (P = 0.039). CONCLUSION: GCA-patients with increased FDG uptake in the aorta may be more prone to develop thoracic aortic dilatation than GCA patients without this sign of aortic involvement.


Assuntos
Aorta/patologia , Arterite de Células Gigantes/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Aorta/diagnóstico por imagem , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Aortografia , Dilatação Patológica/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Seguimentos , Arterite de Células Gigantes/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos , Recidiva , Fatores de Risco , Fatores Sexuais , Tomografia Computadorizada por Raios X
12.
Ultrasound Obstet Gynecol ; 32(5): 633-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18792417

RESUMO

OBJECTIVES: To compare the predictive value of the prenatal observed to expected (o/e) lung volume as measured by fetal magnetic resonance imaging (MRI), based on an algorithm using either the gestational age or fetal body volume (FBV), for neonatal survival of fetuses with isolated congenital diaphragmatic hernia (CDH). METHODS: We included 53 fetuses with a prenatal diagnosis of isolated CDH, 26 without and 27 with prenatal tracheal occlusion, who were assessed by fetal MRI, liveborn after 32 weeks, and in whom follow-up until discharge from the neonatal care unit was available. Measurements of lung volumes were expressed as a percentage of the appropriate mean (o/e total fetal lung volume (TFLV) x 100) either for gestational age or for FBV. Measurements of FBV were expressed as a percentage of the appropriate mean (o/e FBV x 100) for gestation. Fetuses with prenatal intervention were all assessed > or = 24 h after balloon removal. Regression analysis was used to examine the effect on postnatal survival of either o/e TFLV based on gestational age or based on FBV, gestation at delivery, side of CDH, intrathoracic position of the liver and prenatal intervention. Receiver-operating characteristics (ROC) curves were constructed for the prediction of survival by o/e TFLV based on gestational age and o/e TFLV based on FBV, for all fetuses, as well as for those with o/e FBV between 90 and 110% and those with values beyond that range. A power calculation for the number of fetuses needed to show a difference between the ROC curves was performed. RESULTS: Regression analysis demonstrated that o/e TFLV based on gestational age and on FBV were the only independent predictors of postnatal survival. The area under the ROC curve for prediction of postnatal survival from the o/e TFLV based on gestational age was 0.811, and for that based on FBV it was 0.868 (P < 0.001 for both). For fetuses with o/e FBV between 90 and 110%, and those with values < 90% and > 110%, the area for measurements based on gestational age was 0.895 and 0.733, respectively; when based on FBV it was 0.906 and 0.833 (P < 0.01 for all). A minimum of 273 patients would be needed to provide a probability of 90% of detecting a difference between the areas under both ROC curves. CONCLUSIONS: In fetuses with isolated CDH, lung volume as measured by fetal MRI was significantly correlated with survival. Prediction tended to be better by o/e TFLV based on FBV rather than gestational age. The difference in the prediction of survival between o/e TFLV based on FBV or gestational age was dependent on fetal biometry.


Assuntos
Doenças Fetais , Hérnia Diafragmática , Diagnóstico Pré-Natal/métodos , Adulto , Algoritmos , Área Sob a Curva , Estudos Transversais , Reações Falso-Positivas , Doenças Fetais/diagnóstico , Doenças Fetais/mortalidade , Maturidade dos Órgãos Fetais , Idade Gestacional , Hérnia Diafragmática/diagnóstico , Hérnia Diafragmática/mortalidade , Hérnias Diafragmáticas Congênitas , Humanos , Recém-Nascido , Pulmão/embriologia , Medidas de Volume Pulmonar/métodos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Análise de Sobrevida
13.
Radiat Prot Dosimetry ; 129(1-3): 214-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18319282

RESUMO

This study presents a quantitative method for evaluating the detectability of microcalcifications in digital mammography. Four hundred and twenty microcalcifications (with various morphology, size and contrast), simulated with a previously validated method, were used for the creation of image datasets. Lesions were inserted into 163 regions of interests of 59 selected raw digital mammograms with various anatomical backgrounds and acquired with a Siemens Novation DR. After processing, these composite images were scored by experienced radiologists, who located multiple simulated lesions and rated them under conditions of free-search. For statistical analysis, free-response receiver-operating characteristic curves are plotted; the use of jackknife free-response receiver-operating characteristic method has also been investigated. The main advantage of this methodology is that the exact number of inserted microcalcifications is well known and that the lesions are fully characterised in terms of pathology, size, morphology and peak contrast. A first application has been the evaluation of the effect of anatomical background on microcalcifications detection. Preliminary findings in this study indicate that this method may be a promising tool to evaluate factors that have an influence on the detectability of lesions, such as the clinical processing or the viewing conditions.


Assuntos
Doenças Mamárias/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Mamografia/métodos , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Simulação por Computador , Feminino , Humanos , Curva ROC , Intensificação de Imagem Radiográfica/instrumentação , Interpretação de Imagem Radiográfica Assistida por Computador/instrumentação , Tomografia Computadorizada por Raios X
14.
Transplant Proc ; 39(8): 2643-6, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17954198

RESUMO

PURPOSE: Using magnetic resonance imaging, the apparent diffusion coefficient (ADC) is an indicator to assess cerebral ischemia. The aim of this porcine study was to evaluate whether ADC assessed hepatic ischemia during ex vivo hypothermic machine perfusion (HMP) as well as in vivo. METHODS: Ex vivo: ADC of normal versus warm ischemic (WI) livers was assessed during HMP and subsequent rewarming to mimic ischemia-reperfusion injury. As the preservation solution, we used either an acellular solution or diluted blood. WI was induced in the left lobe or in the whole liver and compared 2-hour WI and non-WI. In vivo: One liver was scanned with the left lobe vessels occluded for 2-hour WI and subsequently for 3 hour reperfusion to compare with the right lobe without WI. Aspartate aminotransferase (AST) in the perfusate and morphology were used as surrogates of WI. RESULTS: In all WI livers, AST reached high levels and histology showed severe injury. Ex vivo ADC during acellular perfusion showed negligible differences between the livers with versus without WI, namely, 0.75 x 10(-3) or 0.88 x 10(-3) mm(2)/s during HMP. Ex vivo ADC using sanguineous perfusion showed 1.11 x 10(-3) or 0.83 x 10(-3) mm(2)/s during HMP in regions with versus without WI, respectively, a difference that remained stable during the whole experiment. ADC in vivo decreased from the physiological level of 1.07 x 10(-3) mm(2)/s to 0.75 x 10(-3) mm(2)/s in the first 30 minutes of WI, whereas ADC in the non-WI liver remained constant. CONCLUSION: ADC in vivo decreased during hepatic ischemia, as previously seen in cerebral ischemia. However, the effect of WI on ADC was less clear during ex vivo HMP.


Assuntos
Isquemia Encefálica/patologia , Circulação Hepática , Traumatismo por Reperfusão/patologia , Animais , Imageamento por Ressonância Magnética , Modelos Animais , Suínos
15.
Diabetes ; 30(10): 851-6, 1981 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6115786

RESUMO

Ten patients who had been totally duodeno-pancreatectomized and totally (N = 1) or partially gastrectomized (N = 9) for chronic pancreatitis (N = 9) or pancreatic carcinoma (N = 1) were investigated. None had a measurable basal level of either plasma C-peptide or a C-peptide response to i.v. glucagon. Immunoreactive glucagon (IRG) was present in all patients, and the mean level (69 +/- 8 pg/ml) was not significantly different from the mean observed in normal subjects (81 +/- 16 pg/ml). Plasma IRG was unequivocally stimulated by arginine in 2 of the 10 subjects. The effect of somatostatin on plasma glucose and IRG during an oral glucose tolerance test was studied in 5 of the 10 patients. The effects of somatostatin on spontaneous hyperglycemia, plasma growth hormone, and IRG after withdrawal of insulin treatment was studied in 4 patients. Somatostatin blunted both the hyperglycemic and paradoxical IRG responses to the glucose challenge, and reduced the spontaneous rise of blood glucose that occurred after insulin withdrawal. This latter effect was not related to clear-cut changes in plasma growth hormone or in IRG. These data confirm the existence of circulating IRG in pancreatectomized patients and demonstrate the presence of circulating IRG in a completely gastrectomized and pancreatectomized patient. The somatostatin-induced improvement in glucose tolerance in the oral glucose tolerance test seems to be related to a reduction of the paradoxical IRG response. In contrast, the inhibition by somatostatin of the rise in blood glucose which occurs after insulin withdrawal does not seem to be mediated through IRG or growth hormone.


Assuntos
Duodeno/fisiologia , Gastrectomia , Glucagon/sangue , Hipoglicemiantes , Pancreatectomia , Somatostatina/farmacologia , Adulto , Arginina , Glicemia/metabolismo , Duodeno/cirurgia , Feminino , Glucagon/imunologia , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade
16.
Microbes Infect ; 7(7-8): 969-75, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15994108

RESUMO

Persistence of Mycobacterium tuberculosis is a hypoxia-inducible state in which the bacteria are phenotypically insensitive to currently available antituberculous drugs. In humans, persistent M. tuberculosis is found in granulomatous lesions, either inside macrophages or in necrotic tissue, where the partial oxygen pressure (pO(2)) is very low. Persistent bacteria can remain silent for decades before overt tuberculosis develops. Due to insensitivity to classical drugs, M. tuberculosis persistence prevents rapid and definitive clearance of bacteria. Consequently, therapeutic molecules are required that are both active against persistent bacilli and able to reach their intramacrophagic location. In contrast to its native form, norfloxacin is active in vivo against Mycobacterium bovis BCG present in the lungs when temporarily linked to a macromolecular carrier targeted to macrophages. To study the efficiency of this macromolecular prodrug targeted to persistent mycobacteria confined inside macrophages, we established a short-term in vivo model based on the physiological pO(2) differences between lungs, spleen and liver. Whereas lungs and spleen are well oxygenated, the liver has a low pO(2) due to its portal irrigation. Therefore, studying mycobacteria in the liver yields information about in vivo persistent bacilli exposed to low pO(2). To our knowledge, no similar short-term in vivo model has been published to date. Using this model, we demonstrated the insensitivity to isoniazid of M. bovis BCG present in hypoxic sites, and showed that norfloxacin given as a mannosylated macrophage-targeted prodrug was able to kill these isoniazid-insensitive mycobacteria. This demonstrates that intracellular persistent mycobacteria are amenable to antibiotic treatment.


Assuntos
Antituberculosos/química , Isoniazida/farmacologia , Fígado/microbiologia , Mycobacterium bovis/efeitos dos fármacos , Norfloxacino/química , Animais , Antituberculosos/administração & dosagem , Antituberculosos/farmacologia , Desenho de Fármacos , Farmacorresistência Bacteriana , Feminino , Hipóxia/fisiopatologia , Fígado/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Norfloxacino/administração & dosagem , Norfloxacino/farmacologia , Pró-Fármacos , Baço/microbiologia , Baço/fisiopatologia
17.
J Am Coll Cardiol ; 35(6): 1525-34, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10807456

RESUMO

OBJECTIVES: We sought to evaluate regional morphology and function in patients in their first week after having a reperfused anterior myocardial infarction (MI) using magnetic resonance (MR) myocardial tagging. BACKGROUND: The mechanism of myocardial dysfunction in the remote, noninfarct-related regions is an unresolved issue to date. METHODS: Sixteen patients with a first reperfused transmural anterior MI were studied with MR tagging at 5 +/- 2 days after the event, and the results were compared with those of an age-matched control group regions. The left ventricle (LV) was divided into infarct, adjacent and remote regions. Magnetic resonance tagging provided information on the regional ventricular morphology and function. RESULTS: Morphologically, an increase of the circumferential radius of curvature was found in the remote myocardium, whereas the longitudinal radius of curvature was increased in all regions of the LV. A significant increase in apical sphericity was also found. A significant reduction in strain and function was found not only in the infarct region, but also in the adjacent and remote myocardium. The loss in regional ejection fraction in the remote myocardium (61.4 +/- 11.7% in patients vs. 68.7 +/- 10.0% in control subjects, p < 0.0001) was related to a significant reduction of the longitudinal and circumferential strain, whereas systolic wall thickening was preserved. CONCLUSIONS: Remote myocardial dysfunction contributes significantly to the loss in global ventricular function. This could be secondary to morphologic changes in the infarct region, leading to an increased systolic longitudinal wall stress without loss of intrinsic contractility in the remote regions.


Assuntos
Imageamento por Ressonância Magnética , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Idoso , Feminino , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Infarto do Miocárdio/diagnóstico , Traumatismo por Reperfusão Miocárdica/diagnóstico , Miocárdio/patologia , Volume Sistólico/fisiologia , Sístole/fisiologia , Tomografia Computadorizada de Emissão , Disfunção Ventricular Esquerda/diagnóstico , Função Ventricular Esquerda/fisiologia
18.
Radiat Prot Dosimetry ; 117(1-3): 185-9, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16464834

RESUMO

A growing number of papers report deterministic effects in the skin of patients who have undergone interventional radiological procedures. Dose measurements, and especially skin dose measurements, are therefore increasingly important. Methods and acceptable dosemeters are, however, not clearly defined. This paper is the result of a literature overview with regard to assessing the entrance skin dose during radiological examinations by putting a dosemeter on the patient's skin. The relevant intrinsic characteristics, as well as some examples of clinical use of the different detector types, are presented. In this respect, thermoluminescence, scintillation, semiconductor and film dosemeters are discussed and compared with respect to their practical use.


Assuntos
Radiologia/instrumentação , Radiometria/métodos , Pele/efeitos da radiação , Dosimetria Fotográfica/instrumentação , Dosimetria Fotográfica/métodos , Fluoroscopia/instrumentação , Fluoroscopia/métodos , Humanos , Doses de Radiação , Radiografia Intervencionista/instrumentação , Radiografia Intervencionista/métodos , Radiologia/métodos , Radiometria/instrumentação , Dosimetria Termoluminescente/instrumentação , Dosimetria Termoluminescente/métodos
19.
Radiat Prot Dosimetry ; 117(1-3): 321-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16464839

RESUMO

A diagnostic reference level (DRL) is a dose level for a typical X-ray examination of a group of patients with standard body sizes and for broadly defined types of equipment. These levels are expected not to be exceeded for standard procedures when good and normal practice regarding diagnostic and technical performance is applied. In this paper, we have calculated DRLs for screening mammography in Belgium. The 95th percentile of the mean average glandular dose is 2.46 mGy. The DRL based on polymethyl methacrylate (PMMA) measurements was 2.08 mGy. Correlation coefficient (R) between doses from patient studies and phantom studies was 0.90, with an average underestimation of the phantom measurements of 15% for systems that use only Mo/Mo anode/filter. For the centres that use other anode/filters, there is not enough scientific evidence that a single phantom measurement of a standard PMMA block is representative for the patient dose.


Assuntos
Neoplasias da Mama/diagnóstico , Mamografia/métodos , Programas de Rastreamento/métodos , Bélgica , Relação Dose-Resposta à Radiação , Feminino , Humanos , Imagens de Fantasmas , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiometria , Padrões de Referência , Projetos de Pesquisa , Raios X
20.
Radiat Prot Dosimetry ; 117(1-3): 211-6, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16461498

RESUMO

The goal of this study was to determine the acquisition parameters for a low-dose multi-slice CT protocol and to compare the effective dose and the image quality of this low-dose protocol with the image quality of a clinical multi-slice CT protocol, routinely used for visualisation of the head. The low-dose protocol was derived from a clinical multi-slice CT protocol by lowering mA s and kV and increasing the pitch. The low-dose protocol yielded a dose reduction from 1.5 to 0.18 mSv for a multi-slice CT scan of the whole head, whereas noise in the low-dose CT images was increased. For bone segmentation, noise could be reduced by use of a non-linear edge preserving smoothing filter. Tests on ESP and skull phantom indicated that the accuracy of the measurements on low-dose CT is acceptable for image-based planning of maxillofacial and oral implant surgery, reducing the dose by a factor of 8.


Assuntos
Intensificação de Imagem Radiográfica/métodos , Radiometria/métodos , Cirurgia Bucal/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Imagens de Fantasmas , Próteses e Implantes , Doses de Radiação , Radiografia Panorâmica , Crânio/diagnóstico por imagem
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