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1.
Nucl Med Biol ; 122-123: 108368, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37490805

RESUMO

Advanced ovarian cancer currently has few therapeutic options. Poly(ADP-ribose) polymerase (PARP) inhibitors bind to nuclear PARP and trap the protein-inhibitor complex to DNA. This work investigates a theranostic PARP inhibitor for targeted radiopharmaceutical therapy of ovarian cancer in vitro and PET imaging of healthy mice in vivo. METHODS: [77Br]RD1 was synthesized and assessed for pharmacokinetics and cytotoxicity in human and murine ovarian cancer cell lines. [76Br]RD1 biodistribution and organ uptake in healthy mice were quantified through longitudinal PET/CT imaging and ex vivo radioactivity measurements. Organ-level dosimetry following [76/77Br]RD1 administration was calculated using RAPID, an in-house platform for absorbed dose in mice, and OLINDA for equivalent and effective dose in human. RESULTS: The maximum specific binding (Bmax), equilibrium dissociation constant (Kd), and nonspecific binding slope (NS) were calculated for each cell line. These values were used to calculate the cell specific activity uptake for cell viability studies. The half maximal effective concentration (EC50) was measured as 0.17 (95 % CI: 0.13-0.24) nM and 0.46 (0.13-0.24) nM for PARP(+) and PARP(-) expressing cell lines, respectively. The EC50 was 0.27 (0.21-0.36) nM and 0.30 (0.22-0.41) nM for BRCA1(-) and BRCA1(+) expressing cell lines, respectively. When measuring the EC50 as a function of cellular activity uptake and nuclear dose, the EC50 ranges from 0.020 to 0.039 Bq/cell and 3.3-9.2 Gy, respectively. Excretion through the hepatobiliary and renal pathways were observed in mice, with liver uptake of 2.3 ± 0.4 %ID/g after 48 h, contributing to estimated absorbed dose values in mice of 19.3 ± 0.3 mGy/MBq and 290 ± 10 mGy/MBq for [77Br]RD1 and [76Br]RD1, respectively. CONCLUSION: [77Br]RD1 cytotoxicity was dependent on PARP expression and independent of BRCA1 status. The in vitro results suggest that [77Br]RD1 cytotoxicity is driven by the targeted Meitner-Auger electron (MAe) radiotherapeutic effect of the agent. Further studies investigating the theranostic potential, organ dose, and tumor uptake of [76/77Br]RD1 are warranted.


Assuntos
Neoplasias Ovarianas , Compostos Radiofarmacêuticos , Feminino , Humanos , Animais , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Medicina de Precisão , Linhagem Celular Tumoral , Distribuição Tecidual , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/radioterapia
2.
Br J Dermatol ; 178(3): 749-760, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28815554

RESUMO

BACKGROUND: Striae gravidarum (SG), or stretch marks of pregnancy, begin as erythematous streaks and mature into hypopigmented atrophic bands. OBJECTIVES: In order to investigate molecular alterations that may promote atrophy of SG, we investigated dermal type I collagen fibrils, which provide human skin with support. METHODS: We obtained skin samples of recently developed, erythematous abdominal SG from pregnant women. To examine the organization of collagen fibrils, second-harmonic generation imaging was performed using multiphoton microscopy. Immunostaining was used to determine protein expression and localization of type I procollagen, the precursor of type I collagen fibrils. Real-time polymerase chain reaction was used to determine gene expression levels. RESULTS: In control (hip) and stretched normal-appearing perilesional abdominal skin, dermal collagen fibrils were organized as tightly packed, interwoven bundles. In SG, collagen bundles appeared markedly separated, especially in the mid-to-deep dermis. In the spaces separating these bundles, loosely packed wavy collagen fibrils lacking organization as bundles were present. These disorganized fibrils persisted into the postpartum period and failed to form densely packed bundles. Numerous large fibroblasts displaying type I procollagen expression were in close proximity to the disorganized fibrils, suggesting that the fibrils are newly synthesized. Supporting this possibility, immunostaining and gene expression of type I procollagen were increased throughout the dermis of SG. CONCLUSIONS: Early SG display marked separation of collagen bundles and emergence of disorganized collagen fibrils that fail to form bundles. These alterations may reflect ineffective repair of collagen bundles disrupted by intense skin stretching. Persistent disruption of the collagenous extracellular matrix likely promotes formation and atrophy of SG.


Assuntos
Doenças do Colágeno/patologia , Complicações na Gravidez/patologia , Estrias de Distensão/patologia , Estudos de Casos e Controles , Doenças do Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Feminino , Colágenos Fibrilares/fisiologia , Fibroblastos/metabolismo , Humanos , Gravidez , Complicações na Gravidez/metabolismo , Pró-Colágeno/biossíntese , Pele/irrigação sanguínea , Estrias de Distensão/metabolismo , Adulto Jovem
3.
Oecologia ; 185(4): 537-549, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28963624

RESUMO

Animals face multiple risks while foraging such as the risk of acquiring inadequate energy from food and the risk of predation. We evaluated how two sympatric rabbits (pygmy rabbits, Brachylagus idahoensis, and mountain cottontail rabbits, Sylvilagus nuttallii) that differ in size, use of burrows, and habitat specialization in the sagebrush-steppe of western North America respond to different types and levels of perceived risks (i.e., fitness cost × probability of occurrence), including fiber and toxins in food, exposure to predation, and distance from a refuge. We measured food intake by the rabbits at paired food patches that varied in these risks and used the method of paired comparisons to create a relative ranking of habitat cues, which revealed an animal's perceived risk on a single scale representing an integrated response to a variety of risks. Pygmy rabbits perceived exposure to predation risk and distance from a burrow as riskier than did cottontails, whereas cottontails perceived dietary toxin as riskier. Pygmy rabbits consumed lower quality food, containing higher fiber or toxins, thereby avoided feeding in exposed patches or traveling far from their burrow to forage. In contrast, cottontails fed in exposed patches and traveled farther from the burrow to obtain higher quality food. We have shown how risks can be integrated into a single model that allows animals to reveal their perceptions of risks on a single scale that can be used to create a spatially explicit landscape of risk.


Assuntos
Ingestão de Alimentos , Preferências Alimentares , Herbivoria , Comportamento Predatório , Coelhos/fisiologia , Animais , Artemisia , Tamanho Corporal , Ecossistema , Análise de Alimentos , América do Norte , Fatores de Risco , Toxinas Biológicas/química
5.
Br J Dermatol ; 173(6): 1420-30, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26179468

RESUMO

BACKGROUND: Striae gravidarum (SG), or 'stretch marks' of pregnancy, begin as erythematous streaks, and mature over months to years to become permanent scar-like bands that may be hypopigmented, atrophic and lax. OBJECTIVES: To investigate early molecular alterations that may promote laxity of mature SG, we investigated the dermal elastic fibre network, which provides human skin with elastic properties. METHODS: We obtained skin samples of newly developed, erythematous abdominal SG in healthy pregnant women. The elastic fibre network was examined by Verhoeff elastic staining and immunofluorescence staining of skin sections. Gene expression was measured by real-time polymerase chain reaction. RESULTS: The normal elastic fibre network appeared markedly disrupted in SG, compared with perilesional abdominal skin or control (normal-appearing hip skin). This disruption was accompanied by the emergence of short, disorganized, thin, thread-like 'fibrils', which were observed prominently in the mid-to-deep dermis. These fibrils were rich in tropoelastin (the main component of normal elastic fibres), and persisted into the postpartum period without forming normal-appearing elastic fibres. The emergence of these fibrils was accompanied by increased gene expression of tropoelastin and fibrillin-1, but not other elastic fibre components, including fibrillin-2 and fibulin-1, -2 or -5. CONCLUSIONS: In early SG, the elastic fibre network appears markedly disrupted, and newly synthesized tropoelastin-rich fibrils emerge, likely as a result of uncoordinated synthesis of elastic fibre components. Because they are thin and disorganized, tropoelastin-rich fibrils likely do not function as normal elastic fibres do. These observations provide the foundations for elucidating pathogenic mechanisms by which laxity may develop in SG.


Assuntos
Tecido Elástico/patologia , Estrias de Distensão/patologia , Doenças do Colágeno/patologia , Tecido Elástico/metabolismo , Feminino , Humanos , Gravidez , Transtornos Puerperais/metabolismo , Transtornos Puerperais/patologia , Estrias de Distensão/metabolismo , Tropoelastina/metabolismo , Adulto Jovem
7.
Mol Ecol Resour ; 15(4): 843-54, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25522240

RESUMO

Knowledge of population demographics is important for species management but can be challenging in low-density, wide-ranging species. Population monitoring of the endangered Sonoran pronghorn (Antilocapra americana sonoriensis) is critical for assessing the success of recovery efforts, and noninvasive DNA sampling (NDS) could be more cost-effective and less intrusive than traditional methods. We evaluated faecal pellet deposition rates and faecal DNA degradation rates to maximize sampling efficiency for DNA-based mark-recapture analyses. Deposition data were collected at five watering holes using sampling intervals of 1-7 days and averaged one pellet pile per pronghorn per day. To evaluate nuclear DNA (nDNA) degradation, 20 faecal samples were exposed to local environmental conditions and sampled at eight time points from one to 124 days. Average amplification success rates for six nDNA microsatellite loci were 81% for samples on day one, 63% by day seven, 2% by day 14 and 0% by day 60. We evaluated the efficiency of different sampling intervals (1-10 days) by estimating the number of successful samples, success rate of individual identification and laboratory costs per successful sample. Cost per successful sample increased and success and efficiency declined as the sampling interval increased. Results indicate NDS of faecal pellets is a feasible method for individual identification, population estimation and demographic monitoring of Sonoran pronghorn. We recommend collecting samples <7 days old and estimate that a sampling interval of four to seven days in summer conditions (i.e., extreme heat and exposure to UV light) will achieve desired sample sizes for mark-recapture analysis while also maximizing efficiency [Corrected].


Assuntos
DNA/isolamento & purificação , Fezes/química , Ruminantes/classificação , Ruminantes/genética , Manejo de Espécimes/métodos , Animais , DNA/genética , Manejo de Espécimes/economia
8.
BJOG ; 121(13): 1685-93, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24888772

RESUMO

OBJECTIVE: To assess the frequency of obstructive sleep apnoea among women with and without hypertensive disorders of pregnancy. DESIGN: Cohort study. SETTING: Obstetric clinics at an academic medical centre. POPULATION: Pregnant women with hypertensive disorders (chronic hypertension, gestational hypertension, or pre-eclampsia) and women who were normotensive. METHODS: Women completed a questionnaire about habitual snoring and underwent overnight ambulatory polysomnography. MAIN OUTCOME MEASURES: The presence and severity of obstructive sleep apnoea. RESULTS: Obstructive sleep apnoea was found among 21 of 51 women with hypertensive disorders (41%), but in only three of 16 women who were normotensive (19%, chi-square test, P=0.005). [Author correction added on 16 June 2014, after first online publication: Results mentioned in the abstract were amended.] Non-snoring women with hypertensive disorders typically had mild obstructive sleep apnoea, but >25% of snoring women with hypertensive disorders had moderate to severe obstructive sleep apnoea. Among women with hypertensive disorders, the mean apnoea/hypopnoea index was substantially higher in snorers than in non-snorers (19.9±34.1 versus 3.4±3.1, P=0.013), and the oxyhaemoglobin saturation nadir was significantly lower (86.4±6.6 versus 90.2±3.5, P=0.021). Among women with hypertensive disorders, after stratification by obesity, the pooled relative risk for obstructive sleep apnoea in snoring women with hypertension compared with non-snoring women with hypertension was 2.0 (95% CI 1.4-2.8). CONCLUSIONS: Pregnant women with hypertension are at high risk for unrecognised obstructive sleep apnoea. Although longitudinal and intervention studies are urgently needed, given the known relationship between obstructive sleep apnoea and hypertension in the general population, it would seem pertinent that hypertensive pregnant women who snore should be tested for obstructive sleep apnoea, a condition believed to cause or promote hypertension.


Assuntos
Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão/epidemiologia , Complicações na Gravidez/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Ronco/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Polissonografia , Gravidez , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e Questionários , Adulto Jovem
9.
Br J Radiol ; 87(1039): 20140079, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24827378

RESUMO

OBJECTIVE: To evaluate if vascular and pulmonary parenchymal enhancement values in dual-energy (DE) CT pulmonary angiography (CTPA) can suggest the diagnosis of pulmonary congestion. METHODS: DE-CTPA images of 90 out of 1321 patients negative for pulmonary embolism showed signs of congestive heart failure. We measured DE-derived pulmonary parenchymal [perfused blood volume (PBV)], pulmonary artery (PA) and left atrium (LA) enhancement values in these patients and in 142 control patients. Enhancement values were compared between the populations and correlated with serum values of B-type natriuretic peptide (BNP) and proBNP, where available. RESULTS: No significant difference of PBV but significant differences of mean PA and LA enhancement and individual enhancement differences (PA - LA) were found between the populations. PA - LA was higher in patients with elevated BNP and proBNP and was positively correlated with these values. Receiver operating characteristic analysis revealed a moderate discriminatory power of the PA - LA difference for the presence of cardiac biomarker elevations. CONCLUSION: PBV in DE-CTPA is not altered in patients with signs of congestive heart failure. However, differences in enhancement values in the pre- and post-pulmonary vessels were found in comparison with the control population. ADVANCES IN KNOWLEDGE: Altered pulmonary vascular haemodynamics in pulmonary venous congestion are not reflected in dual-energy-derived PBV maps. In the diagnosis of left heart failure in patients with chest pain and dyspnoea, density measurements in the pulmonary artery and in the left atrium in CTPA images may be a helpful diagnostic tool.


Assuntos
Angiografia/métodos , Insuficiência Cardíaca/diagnóstico , Hiperemia/diagnóstico por imagem , Circulação Pulmonar , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/fisiopatologia , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
10.
Rofo ; 186(2): 151-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23975878

RESUMO

OBJECTIVES: The aim of the study was to determine whether automated quantification of pulmonary perfused blood volume (PBV) in dual-energy computed tomography pulmonary angiography (DE-CTPA) can be used to assess the severity of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Automated quantification of PBV was performed in 25 consecutive CTEPH patients undergoing DE-CTPA. PBV values were correlated with cardiac index and pulmonary vascular resistance quantified by right heart catheterization and walking distance in the 6-minute walk test using Pearson's correlation coefficient and multivariate linear regression analysis to control for age and gender. RESULTS: DE-CTPA derived PBV values inversely correlated with systolic (r = -0.64, p = 0.001) and mean (r = -0.57, p = 0.004) pulmonary arterial pressure. There was a trend for PBV values to inversely correlate with pulmonary vascular resistance (r = -0.20, p = 0.35). No significant correlation was found between PBV values and cardiac index or 6-minute walking distance. These correlations were confirmed to be independent of age and gender on multivariate linear regression analysis. CONCLUSION: DE-CTPA can be used for an automated quantification of pulmonary PBV in chronic thromboembolic pulmonary hypertension. PBV values correlate inversely with systolic and mean pulmonary arterial pressure and can thus be used to estimate the severity of pulmonary hypertension in these patients. Citation Format: • Meinel FG, Graef A, Thierfelder KM et al. Automated Quantification of Pulmonary Perfused Blood Volume by Dual-Energy CTPA in Chronic Thromboembolic Pulmonary Hypertension. Fortschr Röntgenstr 2014; 186: 151 - 156.


Assuntos
Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/fisiopatologia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Angiografia , Volume Sanguíneo , Determinação do Volume Sanguíneo/métodos , Doença Crônica , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Urologe A ; 52(4): 541-5, 2013 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-23483271

RESUMO

Patients with stone disease usually present to the urologist with acute colic pain. For the right choice of therapy the diagnosis needs to be confirmed using one of many imaging methods, including ultrasonography, abdominal radiography, intravenous urography, non-contrast-enhanced computed tomography (CT), CT and magnetic resonance imaging (MRI) urography and dual-energy CT. The techniques differ in the availability, diagnostic sensitivity and specificity and level of radiation exposure. Compared to the others dual-energy CT allows distinction between different stone compositions with high accuracy and can affect the choice of therapy. This article on imaging and diagnosis of urolithiasis discusses the different imaging methods and highlights dual-energy CT and its distinctive features.


Assuntos
Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/tendências , Tomografia Computadorizada por Raios X/tendências , Urografia/métodos , Urolitíase/diagnóstico , Feminino , Humanos , Masculino
12.
Radiologe ; 52(2): 163-6, 2012 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-22271325

RESUMO

This article reports the case of a patient who developed a sudden impairment of gas exchange, renal function and a distended abdomen 13 days after admission to the intensive care unit. The combination of a sudden platelet drop, the timing of heparin administration and evidence of thromboembolic events by computed tomography (CT) led to the suspected diagnosis of heparin-induced thrombocytopenia (HIT) type II which was confirmed by laboratory testing. HIT is a life-threatening complication of heparin anticoagulation and CT is an important diagnostic instrument for detecting the location and extent of thromboembolic manifestations, thereby enabling the initiation of therapy to prevent further complications.


Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/terapia , Heparina/efeitos adversos , Heparina/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Abdominal/métodos , Trombocitopenia/prevenção & controle
13.
Eur J Radiol ; 81(2): 360-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21185141

RESUMO

OBJECTIVE: Aims were (1) to determine the diagnostic accuracy of Dual Energy CT (DECT) in the detection of perfusion defects and (2) to evaluate the potential of DECT to improve the sensitivity for PE. METHODS: 15 patients underwent Dual Energy pulmonary CT angiography (DE CTPA) and a combination of lung perfusion SPECT/CT and ventilation scintigraphy. CTPA and DE iodine distribution maps as well as perfusion SPECT/CT and inhalation scintigrams were reviewed for pulmonary embolism (PE) diagnosis. DECT and SPECT perfusion images were assessed regarding localization and extent of perfusion defects. Diagnostic accuracy of DE iodine (perfusion) maps was determined with reference to SPECT/CT. Diagnostic accuracies for PE detection of DECT and of SPECT/CT with ventilation scintigraphy were calculated with reference to the consensus reading of all modalities. RESULTS: DE CTPA had a sensitivity/specificity of 100%/100% for acute PE, while the combination of SPECT/CT and ventilation scintigraphy had a sensitivity/specificity of 85.7%/87.5%. For perfusion defects, DECT iodine maps had a sensitivity/specificity of 76.7% and 98.2%. CONCLUSION: DECT is able to identify pulmonary perfusion defects with good accuracy. This technique may potentially enhance the diagnostic accuracy in the assessment of PE.


Assuntos
Angiografia/métodos , Imagem de Perfusão/métodos , Embolia Pulmonar/diagnóstico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ventilação Pulmonar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Técnica de Subtração
14.
Mucosal Immunol ; 3(5): 475-86, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20555315

RESUMO

Mucosal immunization may be important for protection against pathogens whose transmission and pathogenesis target the mucosal tissue. The capsid proteins of human papillomavirus (HPV) confer tropism for the basal epithelium and can encapsidate DNA during self-assembly to form pseudovirions (PsVs). Therefore, we produced mucosal vaccine vectors by HPV PsV encapsidation of DNA plasmids expressing an experimental antigen derived from the M and M2 proteins of respiratory syncytial virus (RSV). Intravaginal (IVag) delivery elicited local and systemic M-M2-specific CD8+ T-cell and antibody responses in mice that were comparable to an approximately 10,000-fold higher dose of naked DNA. A single HPV PsV IVag immunization primed for M-M2-specific-IgA in nasal and vaginal secretions. Based on light emission and immunofluorescent microscopy, immunization with HPV PsV-encapsidated luciferase- and red fluorescent protein (RFP)-expressing plasmids resulted in transient antigen expression (<5 days), which was restricted to the vaginal epithelium. HPV PsV encapsidation of plasmid DNA is a novel strategy for mucosal immunization that could provide new vaccine options for selected mucosal pathogens.


Assuntos
Mucosa/metabolismo , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório , Vírus Sinciciais Respiratórios/fisiologia , Vírion/metabolismo , Administração Intravaginal , Administração através da Mucosa , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Células Cultivadas , Epitélio/imunologia , Epitélio/metabolismo , Epitélio/patologia , Epitélio/virologia , Feminino , Imunidade nas Mucosas , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos , Mucosa/imunologia , Mucosa/patologia , Mucosa/virologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/transmissão , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/patogenicidade , Vacinas de DNA , Vagina/patologia , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/metabolismo , Proteínas Virais/genética , Proteínas Virais/imunologia , Proteínas Virais/metabolismo , Vírion/genética , Vírion/patogenicidade
15.
J Anim Sci ; 88(3): 1195-203, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19933428

RESUMO

The objectives were to ascertain whether a yeast cell-wall derivative that was 1.8% beta-glucan in combination with ascorbyl-2-polyphosphate could improve innate immunity and mediate transportation stress in neonatal calves, and to compare the 1.8% beta-glucan yeast cell-wall derivative with a more purified yeast cell-wall derivative (70% beta-glucan). Treatments were 1) an unsupplemented control (CNT); 2) 113 g of a 1.8% (approximately 2%) beta-glucan derivative of yeast cell walls plus 250 mg of l-ascorbic acid phosphate (BG2); or 3) 150 mg of a purified beta-glucan fraction from yeast cell walls (approximately 70% beta-glucan) plus 250 mg/feeding of l-ascorbic acid phosphate (BG70). Calves (n = 39) were transported for 4 h, placed in outdoor hutches, and randomly assigned to treatments. Treatments (mixed with a milk replacer) were individually fed twice daily for 28 d. Calves were offered calf starter, free choice, throughout the study. Weekly starter intake and BW were measured, and fecal samples were collected for Salmonella Typhimurium and Escherichia coli O157:H7 PCR analysis. Blood was collected immediately before transport (d 0) and on d 3, 7, 10, 14, 21, and 28 after transport. Starter intake and DMI were less (P < 0.05) at d 28 for the BG2 and BG70 treatments compared with the CNT treatment. Hematocrit percentages increased (P = 0.002) throughout the experiment. White blood cell counts (treatment x time interaction, P = 0.066) were less for the calves supplemented with BG70 than for those supplemented with BG2 (P = 0.01) or for CNT calves (P = 0.04) on d 28. Granulocyte counts changed (P = 0.04) throughout the experiment. A trend (P = 0.077) for a treatment x time interaction was detected for peripheral blood mononuclear cell counts (PBMC). Counts of PBMC were greater (P = 0.006) for the BG2 treatment compared with the CNT treatment on d 3. Calves given the BG70 supplement had fewer PBMC than those given the BG2 supplement on d 21 (P = 0.03) and 28 (P = 0.05). Fibrinogen concentrations were affected only by time (P = 0.002). Time effects were detected for phagocytosis (P = 0.005), oxidative burst (P < 0.001), expression of cluster of differentiation 18 (P = 0.001), and increased cluster of differentiation 18 (P = 0.006). Phagocytosis was less (P = 0.05) for calves in the BG70 group than for those in the CNT group. Percentage of calves positive for E. coli O157:H7 was greatest (P

Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Ácido Ascórbico/farmacologia , Bovinos/crescimento & desenvolvimento , Leucócitos/efeitos dos fármacos , Fermento Seco/farmacologia , beta-Glucanas/farmacologia , Animais , Animais Recém-Nascidos/imunologia , Animais Recém-Nascidos/psicologia , Peso Corporal/efeitos dos fármacos , Bovinos/imunologia , Bovinos/psicologia , Parede Celular , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Escherichia coli O157/isolamento & purificação , Fezes/microbiologia , Fibrinogênio/análise , Hematócrito/veterinária , Imunidade Inata/efeitos dos fármacos , Contagem de Leucócitos/veterinária , Salmonella typhimurium/isolamento & purificação , Estresse Psicológico/imunologia , Estresse Psicológico/fisiopatologia , Meios de Transporte
16.
Yearb Med Inform ; : 48-58, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19855872

RESUMO

OBJECTIVES: Clinical information system (CIS) developers and implementers have begun to look to other scientific disciplines for new methods, tools, and techniques to help them better understand clinicians and their organizational structures, clinical work environments, capabilities of clinical information and communications technology, and the way these structures and processes interact. The goal of this article is to help CIS researchers, developers, implementers, and evaluators better understand the methods, tools, techniques, and literature of the field of human factors. METHODS: We developed a framework that explains how six key human factors topics relate to the design, implementation, and evaluation of CISs. RESULTS: Using this framework we discuss the following six topics: 1) informatics and patient safety; 2) user interface design and evaluation; 3) workflow and task analysis; 4) clinical decision making and decision support; 5) distributed cognition; and 6) mental workload and situation awareness. CONCLUSIONS: Integrating the methods, tools, and lessons learned from each of these six areas of human factors research early in CIS design and incorporating them iteratively during development can improve user performance, user satisfaction, and integration into clinical workflow. Ultimately, this approach will improve clinical information systems and healthcare delivery.


Assuntos
Ergonomia , Sistemas de Informação , Segurança do Paciente , Interface Usuário-Computador , Tomada de Decisões Assistida por Computador , Humanos , Análise e Desempenho de Tarefas
18.
Radiologe ; 49(10): 942-5, 2009 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-19198792

RESUMO

The presented case shows how difficult it can be to diagnose rare diseases if they present with masses in atypical locations. In an extensive further diagnostic workup other characteristic findings then point to the correct diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Doença de Erdheim-Chester/diagnóstico por imagem , Mamografia , Tomografia Computadorizada por Raios X , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Raras/diagnóstico por imagem
19.
Eur J Obstet Gynecol Reprod Biol ; 140(2): 263-8, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18614272

RESUMO

OBJECTIVE: To assess the predictive value of positron emission tomography computed tomography (PET-CT) imaging in comparison to AGO-scoring in patients planned for cytoreductive surgery in recurrent ovarian cancer. MATERIALS AND METHODS: 33 patients who had received a PET-CT for suspicion of recurrent ovarian cancer between 12/2003 and 08/2007 were included in the retrospective analysis. Indication for PET-CT was based on blood tumor markers Ca 125 or Ca 72-4 and clinical symptoms. Scanning was performed on a Philips Gemini System covering the body from the neck to the thighs one hour after administration of 200MBq fluorodesoxyglucose. PET-CT, surgery and the patient records were reviewed to analyze the predictive value of PET-CT in comparison to an AGO-scoring system based on clinical parameters with regard to the prediction of full resectability of abdominal tumor spread. RESULTS: The statistical analysis of this data showed a sensitivity of 73% (95% C.I., 39-94%) and specificity of 80% (95% C.I., 29-97%) for AGO-scoring with a positive predictive value of 89% and a negative predictive value of 57%. PET-CT achieved a sensitivity of 100% (95% C.I., 72-100%) and specificity of 60% (95% C.I. 15-94%), with a positive predictive value of 85% and negative predictive value of 100%. Further analysis of the data of operated patients with concordant PET-CT and AGO-score (12/16) showed a very good prediction of full resectability with a sensitivity of 100% (95% C.I., 63-100%), specificity of 75% (95% C.I., 20-96%), positive predictive value of 89% and negative predictive value of 100%. CONCLUSION: PET-CT and the AGO-score offer good tools to determine patients for full resectability in recurrent ovarian cancer. PET-CT has a higher negative and the AGO score a higher positive predictive value, and the combination of both improves the diagnostic accuracy.


Assuntos
Recidiva Local de Neoplasia/diagnóstico , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
20.
Eur Radiol ; 18(3): 570-5, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17909817

RESUMO

Cardiac magnetic resonance imaging and echocardiography are currently regarded as standard modalities for the quantification of left ventricular volumes and ejection fraction. With the recent introduction of dual-source computedtomography (DSCT), the increased temporal resolution of 83 ms should also improve the assessment of cardiac function in CT. The aim of this study was to evaluate the accuracy of DSCT in the assessment of left ventricular functional parameters with cardiac magnetic resonance imaging (MRI) as standard of reference. Fifteen patients (two female, 13 male; mean age 50.8 +/- 19.2 years) underwent CT and MRI examinations on a DSCT (Somatom Definition; Siemens Medical Solutions, Forchheim, Germany) and a 3.0-Tesla MR scanner (Magnetom Trio; Siemens Medical Solutions), respectively. Multiphase axial CT images were analysed with a semiautomatic region growing algorithms (Syngo Circulation; Siemens Medical Solutions) by two independent blinded observers. In MRI, dynamic cine loops of short axis slices were evaluated with semiautomatic contour detection software (ARGUS; Siemens Medical Solutions) independently by two readers. End-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF) and stroke volume (SV) were determined for both modalities, and correlation coefficient, systematic error, limits of agreement and inter-observer variability were assessed. In DSCT, EDV and ESV were 135.8 +/- 41.9 ml and 54.9 +/- 29.6 ml, respectively, compared with 132.1 +/- 40.8 ml EDV and 57.6 +/- 27.3 ml ESV in MRI. Thus, EDV was overestimated by 3.7 ml (limits of agreement -46.1/+53.6), while ESV was underestimated by 2.6 ml (-36.6/+31.4). Mean EF was 61.6 +/- 12.4% in DSCT and 57.9 +/- 9.0% in MRI, resulting in an overestimation of EF by 3.8% with limits of agreement at -14.7 and +22.2%. Rank correlation rho values were 0.81 for EDV (P = 0.0024), 0.79 for ESV (P = 0.0031) and 0.64 for EF (P = 0.0168). The kappa value of inter-observer variability were amounted to 0.85 for EDV, ESV and EF. DSCT offers the possibility to quantify left ventricular function from coronary CT angiography datasets with sufficient diagnostic accuracy, adding to the value of the modality in a comprehensive cardiac assessment. The observed differences in the measured values may be due to different post-processing methods and physiological reactions to contrast material injection without beta-blocker medication.


Assuntos
Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X/métodos , Função Ventricular Esquerda/fisiologia , Feminino , Ventrículos do Coração/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tamanho do Órgão , Estudos Prospectivos , Volume Sistólico/fisiologia
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