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1.
J Radiol Prot ; 44(1)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38295404

RESUMEN

Radioactive seed localization (RSL) provides a precise and efficient method for removing non-palpable breast lesions. It has proven to be a valuable addition to breast surgery, improving perioperative logistics and patient satisfaction. This retrospective review examines the lessons learned from a high-volume cancer center's RSL program after 10 years of practice and over 25 000 cases. We provide an updated model for assessing the patient's radiation dose from RSL seed implantation and demonstrate the safety of RSL to staff members. Additionally, we emphasize the importance of various aspects of presurgical evaluation, surgical techniques, post-surgical management, and regulatory compliance for a successful RSL program. Notably, the program has reduced radiation exposure for patients and medical staff.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/métodos , Radioisótopos de Yodo , Mama , Estudios Retrospectivos
2.
Toxicol Appl Pharmacol ; 469: 116545, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37146889

RESUMEN

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is implicated in many developmental and behavioral adverse outcomes in offspring of exposed parents. The objective of this study was to investigate sex-dependent multigenerational effects of preconceptional effects of BaP exposure. Adult wild-type (5D) zebrafish were fed 708 µg BaP/g diet (measured) at a rate of 1% body weight twice/day (14 µg BaP/g fish/day) for 21 days. Fish were spawned using a crossover design, and parental (F0) behavior and reproductive indexes were measured. In offspring, behavioral effects were measured at 96 h post fertilization (hpf) in F1 & F2 larvae, and again when F1s were adults. Compared to controls, there was no significant effect on F0 adult behavior immediately following exposure, but locomotor activity was significantly increased in F1 adults of both sexes. Larval behavior (96 hpf, photomotor response assay) was significantly altered in both the F1 and F2 generations. To assess molecular changes associated with BaP exposure, we conducted transcriptome and DNA methylation profiling in F0 gametes (sperm and eggs) and F1 embryos (10 hpf) from all four crosses. Embryos resulting from the BaP male and control female cross had the most differentially expressed genes (DEGs) and differentially methylated regions (DMRs). Some DMRs were associated with genes encoding chromatin modifying enzymes suggesting regulation of chromatin conformation by DNA methylation. Overall, these results suggest that parental dietary BaP exposure significantly contributes to the multigenerational adverse outcomes.


Asunto(s)
Metilación de ADN , Exposición Paterna , Animales , Femenino , Masculino , Benzo(a)pireno/toxicidad , Benzo(a)pireno/metabolismo , Estudios Cruzados , Expresión Génica , Exposición Paterna/efectos adversos , Semen , Pez Cebra/metabolismo
3.
Clin Exp Immunol ; 189(1): 36-46, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28295207

RESUMEN

The role of viral infections in adverse pregnancy outcomes has gained interest in recent years. Innate immune pattern recognition receptors (PRRs) and their signalling pathways, that yield a cytokine output in response to pathogenic stimuli, have been postulated to link infection at the maternal-fetal interface and adverse pregnancy outcomes. The objective of this study was to investigate the expression and functional response of nucleic acid ligand responsive Toll-like receptors (TLR-3, -7, -8 and -9), and retinoic acid-inducible gene 1 (RIG-I)-like receptors [RIG-I, melanoma differentiation-associated protein 5 (MDA5) and Laboratory of Genetics and Physiology 2(LGP2)] in human term gestation-associated tissues (placenta, choriodecidua and amnion) using an explant model. Immunohistochemistry revealed that these PRRs were expressed by the term placenta, choriodecidua and amnion. A statistically significant increase in interleukin (IL)-6 and/or IL-8 production in response to specific agonists for TLR-3 (Poly(I:C); low and high molecular weight), TLR-7 (imiquimod), TLR-8 (ssRNA40) and RIG-I/MDA5 (Poly(I:C)LyoVec) was observed; there was no response to a TLR-9 (ODN21798) agonist. A hierarchical clustering approach was used to compare the response of each tissue type to the ligands studied and revealed that the placenta and choriodecidua generate a more similar IL-8 response, while the choriodecidua and amnion generate a more similar IL-6 response to nucleic acid ligands. These findings demonstrate that responsiveness via TLR-3, TLR-7, TLR-8 and RIG-1/MDA5 is a broad feature of human term gestation-associated tissues with differential responses by tissue that might underpin adverse obstetric outcomes.


Asunto(s)
Proteína 58 DEAD Box/metabolismo , Helicasa Inducida por Interferón IFIH1/metabolismo , Placenta/inmunología , ARN Helicasas/metabolismo , Receptores de Reconocimiento de Patrones/inmunología , Receptores Toll-Like/metabolismo , Femenino , Humanos , Inmunidad Innata , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Ácidos Nucleicos/inmunología , Poli I-C/inmunología , Embarazo , Receptores Inmunológicos , Transducción de Señal , Técnicas de Cultivo de Tejidos , Receptores Toll-Like/agonistas
4.
Phys Rev Lett ; 119(4): 044802, 2017 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-29341755

RESUMEN

We demonstrate experimentally the resonant excitation of plasma waves by trains of laser pulses. We also take an important first step to achieving an energy recovery plasma accelerator by showing that a plasma wave can be damped by an out-of-resonance trailing laser pulse. The measured laser wakefields are found to be in excellent agreement with analytical and numerical models of wakefield excitation in the linear regime. Our results indicate a promising direction for achieving highly controlled, GeV-scale laser-plasma accelerators operating at multikilohertz repetition rates.

5.
Ann Rheum Dis ; 75(2): 439-48, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25575725

RESUMEN

AIMS: Premature cardiovascular events complicate chronic inflammatory conditions. Low-dose weekly methotrexate (MTX), the most widely used disease-modifying drug for rheumatoid arthritis (RA), reduces disease-associated cardiovascular mortality. MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK). We hypothesised that MTX specifically protects the vascular endothelium against inflammatory injury via induction of AMPK-regulated protective genes. METHODS/RESULTS: In the (NZW×BXSB)F1 murine model of inflammatory vasculopathy, MTX 1 mg/kg/week significantly reduced intramyocardial vasculopathy and attenuated end-organ damage. Studies of human umbilical vein endothelial cells (HUVEC) and arterial endothelial cells (HAEC) showed that therapeutically relevant concentrations of MTX phosphorylate AMPKα(Thr172), and induce cytoprotective genes including manganese superoxide dismutase (MnSOD) and haem oxygenase-1 (HO-1). These responses were preserved when HUVECs were pretreated with tumour necrosis factor-α to mimic dysfunctional endothelium. Furthermore, MTX protected against glucose deprivation-induced endothelial apoptosis. Mechanistically, MTX treatment led to cyclic AMP response element-binding protein (CREB)(Ser133) phosphorylation, while AMPK depletion attenuated this response and the induction of MnSOD and HO-1. CREB siRNA inhibited upregulation of both cytoprotective genes by MTX, while chromatin immunoprecipitation demonstrated CREB binding to the MnSOD promoter in MTX-treated EC. Likewise, treatment of (NZW×BXSB)F1 mice with MTX enhanced AMPKα(Thr172) phosphorylation and MnSOD, and reduced aortic intercellular adhesion molecule-1 expression. CONCLUSIONS: These data suggest that MTX therapeutically conditions vascular endothelium via activation of AMPK-CREB. We propose that this mechanism contributes to the protection against cardiovascular events seen in patients with RA treated with MTX.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Antirreumáticos/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Metotrexato/farmacología , Vasculitis Reumatoide/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Hemo-Oxigenasa 1/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Transferasas de Hidroximetilo y Formilo/metabolismo , Inflamación , Ratones , Complejos Multienzimáticos/metabolismo , Nucleótido Desaminasas/metabolismo , Fosforilación , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa
6.
Clin Exp Immunol ; 182(1): 69-80, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26032049

RESUMEN

Leucocytes respond rapidly to pathogenic and other insults, with responses ranging from cytokine production to migration and phagocytosis. These are bioenergetically expensive, and increased glycolytic flux provides adenosine triphosphate (ATP) rapidly to support these essential functions. However, much of this work is from animal studies. To understand more clearly the relative role of glycolysis and oxidative phosphorylation in human leucocytes, especially their utility in a translational research setting, we undertook a study of human peripheral blood mononuclear cells (MNCs) bioenergetics. Glycolysis was essential during lipopolysaccharide (LPS)-mediated interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α production, as 2-deoxy-D-glucose decreased significantly the output of all three cytokines. After optimizing cell numbers and the concentrations of all activators and inhibitors, oxidative phosphorylation and glycolysis profiles of fresh and cryopreserved/resuscitated MNCs were determined to explore the utility of MNCs for determining the bioenergetics health profile in multiple clinical settings. While the LPS-induced cytokine response did not differ significantly between fresh and resuscitated cells from the same donors, cryopreservation/resuscitation significantly affected mainly some measures of oxidative phosphorylation, but also glycolysis. Bioenergetics analysis of human MNCs provides a quick, effective means to measure the bioenergetics health index of many individuals, but cryopreserved cells are not suitable for such an analysis. The translational utility of this approach was tested by comparing MNCs of pregnant and non-pregnant women to reveal increased bioenergetics health index with pregnancy but significantly reduced basal glycolysis and glycolytic capacity. More detailed analysis of discrete leucocyte populations would be required to understand the relative roles of glycolysis and oxidative phosphorylation during inflammation and other immune responses.


Asunto(s)
Adenosina Trifosfato/metabolismo , Glucólisis/fisiología , Leucocitos Mononucleares/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Adulto , Antimetabolitos/farmacología , Células Cultivadas , Criopreservación , Desoxiglucosa/farmacología , Femenino , Glucólisis/efectos de los fármacos , Humanos , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , L-Lactato Deshidrogenasa/metabolismo , Lipopolisacáridos/inmunología , Embarazo , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto Joven
7.
Clin Exp Allergy ; 45(10): 1566-78, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25845975

RESUMEN

BACKGROUND: Exposure to damp indoor environments is associated with increased risk of eczema, allergy and asthma. The role of dampness-related exposures and risk of allergic diseases are yet to be fully explored in the US population. OBJECTIVE: We assess whether exposure to fungi, house dust mites and endotoxin increases the risk of eczema, allergy and asthma in children and adults participating in NHANES 2005-2006. METHODS: A total of 8412 participants (2849 were children aged between 6 and 17 years) were recruited in the 2005-2006 survey. We used multiple logistic regression to investigate whether mildew/musty odour and increased concentrations of Alternaria alternata allergen, Aspergillus fumigatus antigens, house dust mite and endotoxin antigens increase the risk of eczema, allergy and asthma. We stratified models by total IgE < 170 and ≥ 170 KU/L to assess allergic and non-allergic asthma outcomes. Exposure to multiple biological agents and risk of reporting eczema, allergy and asthma were also investigated. RESULTS: Reporting of a mildew/musty odour was associated with increased risk of childhood asthma (OR 1.60; 95% CI 1.17-2.19), and adult eczema, allergy and asthma (OR 1.92; 95% CI 1.39-2.63, OR 1.59 95% CI 1.26-2.02 and OR 1.61 95% CI 1.00-2.57, respectively). Risk of asthma was associated with total IgE ≥ 170 KU/L in children (OR 1.81; 95% CI 1.01-3.25) and total IgE < 170 KU/L in adults (OR 1.91; 95% CI 1.07-3.42). Children and adults exposed to more than eight biological agents present in the home were at reduced risk of eczema (OR 0.17; 95% CI 0.04-0.77) and asthma (OR 0.49; 95% CI 0.25-0.97), respectively. CONCLUSION: Exposure to a mildew/musty odour, as a proxy for exposure to fungus, was implicated in an increased risk of atopic diseases. Sensitisation may play a different role in children and adults, and exposure to multiple allergens may reduce the risk of atopic disease.


Asunto(s)
Contaminación del Aire Interior/efectos adversos , Alérgenos/toxicidad , Alternaria , Aspergillus fumigatus , Asma/epidemiología , Eccema/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/etiología , Niño , Eccema/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos
8.
Clin Exp Allergy ; 45(5): 844-858, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25772780

RESUMEN

Allergic disease can be viewed as an early manifestation of immune dysregulation. Environmental exposures including maternal inflammation, diet, nutrient balance, microbial colonization and toxin exposures can directly and indirectly influence immune programming in both pregnancy and the postnatal period. The intrauterine microclimate is critical for maternal and fetal immunological tolerance to sustain viable pregnancy, but appears susceptible to environmental conditions. Targeting aspects of the modern environment that promote aberrant patterns of immune response is logical for interventions aimed at primary prevention of allergic disease. Defining the mechanisms that underpin both natural and therapeutic acquisition of immunological tolerance in childhood will provide insights into the drivers of persistent immune dysregulation. In this review, we summarize evidence that allergy is a consequence of intrauterine and early life immune dysregulation, with specific focus on contributing environmental risk factors occurring preconception, in utero and in the early postnatal period. We explore the immunological mechanisms which underpin tolerance and persistence of allergic disease during childhood. It is likely that future investigations within these two domains will ultimately provide a road map for the primary prevention of allergic disease.


Asunto(s)
Hipersensibilidad/etiología , Factores de Edad , Alérgenos/inmunología , Animales , Ambiente , Exposición a Riesgos Ambientales , Epigénesis Genética , Femenino , Alimentos , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Hipersensibilidad/metabolismo , Tolerancia Inmunológica/genética , Tolerancia Inmunológica/inmunología , Inmunidad , Exposición Materna , Metabolómica , Microbiota , Embarazo , Efectos Tardíos de la Exposición Prenatal
9.
Anaesthesia ; 70(9): 1066-72, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25920728

RESUMEN

It has been suggested that giving cell-salvaged blood through a leucocyte depletion filter can cause hypotension due to bradykinin released when factor XII and platelets are activated by the negatively charged surface of the filter. We measured the concentration of bradykinin and cysteinyl leukotrienes in cell-salvaged blood sampled before and after passage through a negatively charged leucodepletion filter in 24 consecutive patients with gynaecological or bowel cancer undergoing elective surgery with cell salvage. In no case was an increase in bradykinin concentration observed after passage through the filter; in 23 patients the post-filtration bradykinin concentration was zero (p = 0.007). The change in the concentration of cysteinyl leukotrienes detected during passage across the filter was not statistically significant (p = 0.1). Our findings do not support the suggestion that either bradykinin or cysteinyl leukotrienes are generated in cell-salvaged blood during passage through leucodepletion filters.


Asunto(s)
Bradiquinina/análisis , Cisteína/análisis , Filtración/métodos , Leucaféresis/métodos , Leucotrienos/análisis , Neoplasias/sangre , Transfusión de Sangre Autóloga , Femenino , Humanos , Masculino , Proyectos Piloto
10.
J Clin Microbiol ; 52(6): 2039-45, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24671798

RESUMEN

Galactomannan detection in bronchoalveolar lavage (BAL) fluid samples (GM test) is currently considered the gold standard test for diagnosing invasive pulmonary aspergillosis (IPA). The limitations, however, are the various turnaround times and availability of testing. We compared the performance of GM testing with that of conventional culture, an Aspergillus lateral-flow-device (LFD) test, a beta-d-glucan (BDG) test, and an Aspergillus PCR assay by using BAL fluid samples from immunocompromised patients. A total of 78 BAL fluid samples from 78 patients at risk for IPA (74 samples from Graz and 4 from Mannheim) collected between December 2012 and May 2013 at two university hospitals in Austria and Germany were included. Three patients had proven IPA, 14 probable IPA, and 17 possible IPA, and 44 patients had no IPA. The diagnostic accuracies of the different methods for probable/proven IPA were evaluated. The diagnostic odds ratios were the highest for the GM, PCR, and LFD tests. The sensitivities for the four methods (except culture) were between 70 and 88%. The combination of the GM (cutoff optical density index [ODI], >1.0) and LFD tests increased the sensitivity to 94%, while the combination of the GM test (>1.0) and PCR resulted in 100% sensitivity (specificity for probable/proven IPA, 95 to 98%). The performance of conventional culture was limited by low sensitivity, while that of the BDG test was limited by low specificity. We evaluated established and novel diagnostic methods for IPA and found that the Aspergillus PCR, LFD, and GM tests were the most useful methods for diagnosing the disease by using BAL fluid samples. In particular, the combination of the GM test and PCR or, if PCR is not available, the LFD test, allows for sensitive and specific diagnosis of IPA.


Asunto(s)
Antígenos Fúngicos/análisis , Aspergillus/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/microbiología , ADN de Hongos/análisis , Aspergilosis Pulmonar Invasiva/diagnóstico , Técnicas Microbiológicas/métodos , Adulto , Anciano , Aspergillus/química , Aspergillus/crecimiento & desarrollo , Austria , Líquido del Lavado Bronquioalveolar/química , Cromatografía de Afinidad/métodos , Femenino , Galactosa/análogos & derivados , Alemania , Glucanos/análisis , Hospitales Universitarios , Humanos , Huésped Inmunocomprometido , Masculino , Mananos/análisis , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Estudios Prospectivos , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
11.
Clin Exp Allergy ; 44(5): 631-41, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24471926

RESUMEN

Exposure to dampness and fungi in the home is a known risk factor for individuals with allergic asthma. Inadequate heating and ventilation may lead to dampness and concomitant increased exposure to spores of allergenic fungi such as Aspergillus and Penicillium. These fungi have been cultured from sputum of asthmatic and non-asthmatic individuals, and implicated in the initiation or exacerbation of asthma. Indoor environmental factors influence the presence and concentrations of fungal propagules and, in turn, risk of asthma outcomes. This review aims to identify modifiable risk factors in the built environment that have been shown to influence fungal composition indoors, and to examine this association with the risk of asthma development and/or exacerbation. A complex interaction between residential characteristics, the built environment and the behaviour of people regulate the diversity and concentrations of indoor fungi. Modifiable factors include build age, architectural design, level of maintenance, variations in construction materials, presence of pets, heating and ventilation patterns. Risk of fungal contamination and asthma outcomes are also influenced by low occupant awareness concerning potential health effects and socio-economic factors. Addressing these factors provides an opportunity to improve future housing interventions, though it is not clear how the built environment and occupant behaviours interact to modify the diversity of indoor fungi and resultant risk of asthma. A combination of housing improvements combined with awareness programmes and the alleviation of fuel poverty can be used to lower the allergen burden associated with damp homes. Further research is needed to identify factors that regulate the concentration and diversity of indoor fungi and how this may act as a modifier for asthma outcomes.


Asunto(s)
Contaminación del Aire Interior/efectos adversos , Alérgenos/inmunología , Asma/etiología , Hongos/inmunología , Animales , Asma/epidemiología , Biodiversidad , Humanos , Riesgo
12.
Dev Neurosci ; 35(2-3): 130-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23548575

RESUMEN

Toll-like receptors (TLRs) are members of the pattern recognition receptor family that detect components of foreign pathogens or endogenous molecules released in response to injury. Recent studies demonstrate that TLRs also have a functional role in regulating neuronal proliferation in the developing brain. This study investigated cellular expression of TLR3 using immunohistochemistry on human brain tissue. The tissue sections analysed contained anterior and lateral periventricular white matter from the frontal and parietal lobes in post-mortem neonatal cases with a postmenstrual age range of 23.6-31.4 weeks. In addition to preterm brains without overt pathology (control), preterm pathology cases with evidence of white matter injuries (WMI) were also examined. In order to identify TLR-positive cells, we utilized standard double-labelling immunofluorescence co-labelling techniques and confocal microscopy to compare co-expression of TLR3 with a neuronal marker (NeuN) or with glial markers (GFAP for astrocytes, Iba-1 for microglia and Olig2 for oligodendrocytes). We observed an increase in the neuronal (28 vs. 17%) and astroglial (38 vs. 21%) populations in the WMI group compared to controls in the anterior regions of the periventricular white matter in the frontal lobe. The increase in neurons and astrocytes in the WMI cases was associated with an increase in TLR3 immunoreactivity. This expression was significantly increased in the astroglia. The morphology of the TLR3 signal in the control cases was globular and restricted to the perinuclear region of the neurons and astrocytes, whilst in the cases of WMI, both neuronal, axonal and astroglial TLR3 expression was more diffuse (i.e., a different intracellular distribution) and could be detected along the extensions of the processes. This study demonstrates for the first time that neurons and glial cells in human neonatal periventricular white matter express TLR3 during development. The patterns of TLR3 expression were altered in the presence of WMI, which might influence normal developmental processes within the immature brain. Identifying changes in TLR3 expression during fetal development may be key to understanding the reduced volumes of grey matter and impaired cortical development seen in preterm infants.


Asunto(s)
Encéfalo/metabolismo , Recien Nacido Extremadamente Prematuro/metabolismo , Neuroglía/metabolismo , Neuronas/metabolismo , Receptor Toll-Like 3/biosíntesis , Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Lesiones Encefálicas/metabolismo , Humanos , Recien Nacido Extremadamente Prematuro/crecimiento & desarrollo , Recién Nacido , Fibras Nerviosas Mielínicas/metabolismo , Fibras Nerviosas Mielínicas/patología , Receptor Toll-Like 3/análisis
13.
Infection ; 41(6): 1163-9, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23661288

RESUMEN

PURPOSE: The detection of galactomannan in serum is a cornerstone for the diagnosis of invasive fungal disease (IFD). Because a delay in treatment initiation is associated with a poor outcome, the results have to be available promptly. However, due to methodological and economic reasons, the test frequencies of the commonly used galactomannan assays vary between daily to weekly, meaning that results may be available too late to be clinically useful. The novel Aspergillus lateral-flow device (Aspergillus-LFD) is a rapid test that may overcome these limitations. METHODS: We compared the diagnostic performance of the Aspergillus-LFD and the Platelia® Aspergillus EIA (GM-EIA) in serum from 101 patients during and after allogeneic haematopoietic stem cell transplantation (HSCT). Clinical data and sera were collected prospectively and patients classified according to the European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) 2008 guidelines. RESULTS: By the end of hospitalisation, one proven, nine probable and 20 possible cases of IFD were identified. Depending on the number of positive serum samples required for test positivity, the sensitivities, specificities and diagnostic odds ratios in patients with proven and probable IFD were as follows. One positive serum required: Aspergillus-LFD 40.0 %, 86.8 % and 3.03; GM-EIA 40.0 %, 89.0 % and 3.64. Two positive sera required: Aspergillus-LFD 20.0 %, 97.8 % and 11.13; GM-EIA 30.0 %, 98.9 % and 38.57. Although the GM-EIA was positive in a higher percentage of samples, this did not result in an earlier diagnosis. CONCLUSIONS: If used as a screening test (one positive serum required for test positivity) or to rule out IFD, the Aspergillus-LFD has shown a comparable diagnostic performance to the GM-EIA. However, if the results have to be confirmed by a second positive serum, the GM-EIA exhibited superior sensitivity. In terms of practicability, the Aspergillus-LFD has demonstrated to be a quick (15 min) and easy-to-use test for single-patient detection of Aspergillus antigens.


Asunto(s)
Aspergilosis/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Mananos/sangre , Adulto , Anciano , Aspergillus/aislamiento & purificación , Biomarcadores/sangre , Cromatografía de Afinidad/instrumentación , Cromatografía de Afinidad/métodos , Reacciones Falso Positivas , Femenino , Galactosa/análogos & derivados , Humanos , Técnicas para Inmunoenzimas/instrumentación , Técnicas para Inmunoenzimas/métodos , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Adulto Joven
14.
Br J Biomed Sci ; 70(2): 67-74, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23888608

RESUMEN

The QBC Star haematology system includes the QBC Star centrifugal analytical analyser and the QBC Star tube system. Together, they are capable of producing a haematology profile on venous or capillary whole blood. The aim of this study is to compare full blood count (FBC) including differential white cell count performance between the QBC Star analyser and a gold standard Sysmex XE-2100 haematology analyser. The FBC performance was evaluated according to the National Committee for Clinical Laboratory Standards (NCCLS) document H20-A. Imprecision, correlation and linearity studies all showed excellent results. Overall, the haemoglobin, haematocrit, white cell count (WCC) and platelet count parameters showed excellent correlation. Mean corpuscular haemoglobin concentration (MCHC) results showed poor comparability. The white cell differential parameters showed good correlation within certain clinically significant limits. Imprecision for haemoglobin, haematocrit, WCC, MCHC and platelet count was considered acceptable. The re-read function was found to be stable over the five-hour testing period under the authors' laboratory environmental conditions. The subjective assessment by biomedical scientist staff demonstrated that the system was user friendly, required little maintenance, and no user calibration was required. Staff considered the user manual to be excellent. Overall, the QBC Star appears to be an excellent point-of-care (POC) dry haematology analyser that delivers clinically significant nine-parameter complete blood count and will make a good POC analyser for use in field hospitals, research, screening programmes, GP surgeries as well as in emergency and intensive care units. It is a health and safety-friendly analyser considering the fact that it uses dry haematology reagents instead of the bulky wet reagents that are often associated with liquid biohazard waste.


Asunto(s)
Recuento de Células Sanguíneas/instrumentación , Hematología/instrumentación , Sistemas de Atención de Punto , Recuento de Células Sanguíneas/normas , Calibración , Diseño de Equipo , Índices de Eritrocitos , Hematócrito/instrumentación , Hematócrito/normas , Hemoglobinas , Humanos , Recuento de Plaquetas/instrumentación , Recuento de Plaquetas/normas , Reproducibilidad de los Resultados
15.
Nat Genet ; 16(4): 407-9, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9241283

RESUMEN

Myotonic dystrophy, or dystrophia myotonica (DM), is a highly variable multisystem disease in which the classic adult-onset form displays progressive muscle wasting, cataracts, heart block, gonadal atrophy, insulin resistance and neuropsychiatric impairment. Its genetic basis is an expansion of CTG trinucleotide repeats in the DMPK protein kinase gene. Among the triplet repeat expansion disorders, DM is distinguished by the extended length of the repeat tract (5-13 kb in postmortem tissue) and its location in the 3' untranslated region of the gene that contains it. The pathophysiological mechanism for multisystem degeneration in DM is not understood. In contrast to the profound muscle wasting that characterizes advanced DM, only minor histopathological abnormalities have occurred in DMPK knockout mice or in mice that overexpress a human DMPK transgene, making it unlikely that changes in DMPK activity provide a unitary explanation for the disease. A DNAse hypersensitive site that maps 0.7 kb downstream (centromeric) from the CTG repeats is eliminated on DM chromosomes. This finding indicates that the repeat expansion may alter the adjacent chromatin structure and raises the possibility that it may also affect the expression of flanking genes. An interesting candidate flanking gene is DMAHP, a recently discovered homeodomain-encoding gene. We show here that DMAHP expression in myoblasts, muscle and myocardium is reduced by the DM mutation is cis, and the magnitude of this effect depends on the extent of CTG repeat expansion. These observations support the hypothesis that DMAHP participates in the pathophysiology of DM.


Asunto(s)
Regulación de la Expresión Génica , Proteínas de Homeodominio/genética , Distrofia Miotónica/genética , Repeticiones de Trinucleótidos , Animales , Secuencia de Bases , Cartilla de ADN , Exones , Humanos , Ratones , Datos de Secuencia Molecular , Polimorfismo Genético , ARN Mensajero
16.
Nat Genet ; 25(4): 440-3, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10932191

RESUMEN

As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.


Asunto(s)
Genes/fisiología , Genoma , Mutagénesis/genética , Animales , Animales Recién Nacidos , Mapeo Cromosómico , Cruzamientos Genéticos , Criopreservación , Etilnitrosourea/farmacología , Femenino , Fertilización In Vitro , Genes/efectos de los fármacos , Genes/genética , Pruebas Hematológicas , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Actividad Motora/genética , Mutagénesis/efectos de los fármacos , Mutágenos/farmacología , Mutación , Fenotipo , Factores de Tiempo , Destete
17.
Phys Rev E ; 108(5-2): 055211, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38115527

RESUMEN

We present measurements of the temporal decay rate of one-dimensional (1D), linear Langmuir waves excited by an ultrashort laser pulse. Langmuir waves with relative amplitudes of approximately 6% were driven by 1.7J, 50fs laser pulses in hydrogen and deuterium plasmas of density n_{e0}=8.4×10^{17}cm^{-3}. The wakefield lifetimes were measured to be τ_{wf}^{H_{2}}=(9±2) ps and τ_{wf}^{D_{2}}=(16±8) ps, respectively, for hydrogen and deuterium. The experimental results were found to be in good agreement with 2D particle-in-cell simulations. In addition to being of fundamental interest, these results are particularly relevant to the development of laser wakefield accelerators and wakefield acceleration schemes using multiple pulses, such as multipulse laser wakefield accelerators.

18.
Mar Pollut Bull ; 171: 112704, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34298328

RESUMEN

Loss of sediment and particulate nutrients in runoff from the extensive grazing lands of the Fitzroy Basin, central Queensland, continue to contribute to the declining health of the Great Barrier Reef. This study measured differences in hydrology and water quality from conservative and heavy grazing pressures on rundown improved grass pastures in the Fitzroy Basin. Conservative grazing pressure was defined as the safe long-term carrying capacity for rundown buffel grass pasture, whereas heavy grazing pressure was defined as the recommended stocking rate for newly established buffel grass pasture. Heavy grazing of rundown pasture resulted in 2.5 times more bare ground and only 8% of the pasture biomass compared to conservative grazing. Heavy grazing also resulted in 3.6 times more total runoff and 3.3 times the peak runoff rate compared to conservative grazing. Loads of total suspended solids, nitrogen and phosphorus in runoff were also greater from heavy than conservative grazing.


Asunto(s)
Nitrógeno , Fósforo , Australia , Nitrógeno/análisis , Fósforo/análisis , Poaceae , Queensland
20.
Eur Eat Disord Rev ; 18(3): 220-33, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20443205

RESUMEN

There is a dearth of literature evaluating day patient treatment for eating disorders based upon the targeted goals of treatment, to conclude that day patient programmes are effective. This study aimed to explore the effectiveness of an innovative day patient programme by examining whether the seven key treatment goals improved across treatment and were maintained 3 months after discharge. Of the 58 participants who completed measures assessing BMI, eating disorder cognitions, behaviours, core beliefs, readiness to change, quality of life and perpetuating factors at admission, discharge and follow-up, 44 completed the day programme with 14 non-completers. The results demonstrated that all seven treatment goals improved across treatment and the improvements were maintained or further improved at 3 month follow-up. The results are discussed in context of the published day patient programme literature with implications for future research to maximise optimal treatment outcomes from day patient treatment.


Asunto(s)
Terapia Cognitivo-Conductual/métodos , Centros de Día , Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Adulto , Índice de Masa Corporal , Objetivos , Conductas Relacionadas con la Salud , Humanos , Nueva Gales del Sur , Evaluación de Programas y Proyectos de Salud , Calidad de Vida , Resultado del Tratamiento
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