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2.
Clin Radiol ; 77(6): e401-e416, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35393101

RESUMO

Institutional variations in parathyroid adenoma localisation are largely dictated by local experience and availability of imaging investigations, with no consensus on the optimal approach. This review evaluates the role of multiple imaging techniques in primary hyperparathyroidism and highlights their advantages and limitations in different clinical contexts. A clinico-radiological review of parathyroid imaging techniques is illustrated with example cases and data from the literature. These include high-resolution ultrasound, 99mTc-sestamibi planar scintigraphy with and without thyroid subtraction techniques, integrated 99mTc-sestamibi single-photon-emission computed tomography (SPECT)/computed tomography (CT), four-dimensional (4D) CT, and other techniques, such as magnetic resonance imaging, integrated 18F-choline/11C-methionine positron-emission tomography (PET)/CT and angiographic selective venous sampling. The crucial role of parathyroid embryological and gross anatomy in informing the surgical approach to parathyroidectomy is discussed. Finally, a systematic approach to imaging is proposed to maximise the accuracy of imaging localisation of parathyroid lesions, which is crucial for optimal patient management.


Assuntos
Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Imagem Multimodal , Glândulas Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton Único
3.
Clin Radiol ; 76(1): 78.e9-78.e17, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33036778

RESUMO

AIM: To determine whether machine learning-based radiomic feature analysis of baseline integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) computed tomography (CT) predicts disease progression in patients with locally advanced larynx and hypopharynx squamous cell carcinoma (SCC) receiving (chemo)radiotherapy. MATERIALS AND METHODS: Patients with larynx and hypopharynx SCC treated with definitive (chemo)radiotherapy at a specialist cancer centre undergoing pre-treatment PET-CT between 2008 and 2017 were included. Tumour segmentation and radiomic analysis was performed using LIFEx software (University of Paris-Saclay, France). Data were assigned into training (80%) and validation (20%) cohorts adhering to TRIPOD guidelines. A random forest classifier was created for four predictive models using features determined by recursive feature elimination: (A) PET, (B) CT, (C) clinical, and (D) combined PET-CT parameters. Model performance was assessed using area under the curve (AUC) receiver operating characteristic (ROC) analysis. RESULTS: Seventy-two patients (40 hypopharynx 32 larynx tumours) were included, mean age 61 (range 41-77) years, 50 (69%) were men. Forty-five (62.5%) had chemoradiotherapy, 27 (37.5%) had radiotherapy alone. Median follow-up 26 months (range 12-105 months). Twenty-seven (37.5%) patients progressed within 12 months. ROC AUC for models A, B, C, and D were 0.91, 0.94, 0.88, and 0.93 in training and 0.82, 0.72, 0.70, and 0.94 in validation cohorts. Parameters in model D were metabolic tumour volume (MTV), maximum CT value, minimum standardized uptake value (SUVmin), grey-level zone length matrix (GLZLM) small-zone low grey-level emphasis (SZLGE) and histogram kurtosis. CONCLUSION: FDG PET-CT derived radiomic features are potential predictors of early disease progression in patients with locally advanced larynx and hypopharynx SCC.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neoplasias Laríngeas/diagnóstico por imagem , Neoplasias Laríngeas/patologia , Aprendizado de Máquina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Feminino , Fluordesoxiglucose F18 , Humanos , Hipofaringe/diagnóstico por imagem , Hipofaringe/patologia , Neoplasias Laríngeas/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos
4.
Clin Radiol ; 75(1): 79.e1-79.e7, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31601386

RESUMO

AIM: To analyse the additional clinical value of protocol-driven and selective use of multidetector single-photon-emission tomography/computed tomography (SPECT/CT) in oncology patients undergoing whole-body bone scintigraphy (BS) and to analyse reporter confidence in diagnosis with and without SPECT/CT. MATERIALS AND METHODS: During a 2-year period, 2,954 whole-body BS examinations were performed in oncology patients, with 444 (15%) undergoing additional protocol-driven SPECT/CT. Retrospective evaluation of planar BS and SPECT/CT images was performed by two experienced dual-trained nuclear medicine radiologists. The BS and SPECT/CT images were graded blindly using a five-point scale designed to evaluate the likelihood of a lesion being benign or malignant. Interpretation was applied on a per-patient basis. RESULTS: There was a 74.5% increase in definitive diagnostic classification and a 26.6% reduction in equivocal findings with SPECT/CT when compared to BS alone (p<0001). Of cases initially classified as "probably benign" on BS, 5.1% (10/193) were reclassified to "probably malignant" (1%) or "malignant" (4.1%) using the SPECT/CT data. The highest impact in reporter confidence was seen with SPECT/CT in the interpretation of lesions within the pelvis (34%), ribs (23%), lumbar spine (22%), and thoracic spine (21%). CONCLUSION: Protocol-driven, selective use of SPECT/CT imaging to augment planar BS reduces equivocal findings and improves reporter confidence whilst minimising the impact on patient and reporting workflows.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Algoritmos , Protocolos Clínicos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99m , Imagem Corporal Total , Fluxo de Trabalho
5.
Clin Radiol ; 74(9): 702-711, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31272599

RESUMO

AIM: To evaluate the real-world performance of the British Thyroid Association (BTA) U classification, specifically focusing on radiology-pathology correlation and to glean learning points. METHODS AND MATERIALS: Adults undergoing a neck ultrasound for thyroid nodules were reviewed over a period of 1-year. Data including demographics, nodule characteristics, BTA grading, and cytology/histopathology were retrieved with a minimum 24-month follow-up. RESULTS: Of 1,225 graded nodules in 964 patients, cytology and/or histology were available for 300 (24%). 57 cancers were detected. Of 24 (2%) U5 nodules, 14 were malignant, of 51 (4%) U4, 22 were malignant, of 256 (21%) U3, 20 were malignant, and from 894 (73%) U2 nodules, one cancer was discovered. BTA U grading with fine-needle aspiration (FNA)/core biopsy achieved 96.5% sensitivity, 93.7% specificity, and 93.9% accuracy compared to excision. There was no association between nodule size and rate of malignancy. CONCLUSION: This is the first study to validate the use of the BTA U-grading system in UK clinical practice. The BTA U-grading system is a robust and reliable method of evaluating the risk of malignancy in thyroid nodules with a high negative predictive value. Key learning points gleaned from the study were accurate assessment of nodule echogenicity, careful evaluation of solid-cystic nodules, optimising ultrasound technique, and the low-risk nature of U3 nodules.


Assuntos
Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia/métodos , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina , Diagnóstico Diferencial , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Sensibilidade e Especificidade
6.
Clin Oncol (R Coll Radiol) ; 31(4): 212-218, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30553580

RESUMO

AIM: There are few data to inform on the use of response assessment 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography-computed tomography (PET-CT) following radical radiotherapy without chemotherapy for head and neck squamous cell carcinoma (HNSCC). This retrospective study evaluated the accuracy of PET-CT in HNSCC following radical radiotherapy. MATERIALS AND METHODS: In total, 138 patients with HNSCC treated with radical radiotherapy without chemotherapy who underwent a baseline and response assessment FDG PET-CT were identified. FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes. RESULTS: The median follow-up was 26 months. FDG-avid disease at baseline was present for the primary site and lymph nodes in 118 and 86 patients, respectively. With regard to the primary tumour, the negative predictive value (NPV) of a complete metabolic response (CMR) was 95%; the positive predictive value (PPV) of equivocal uptake and a positive scan were 6% and 82%, respectively. The likelihood ratios for a CMR, equivocal and positive scans of the primary site were 0.19, 0.22, 14.8, respectively. With regard to lymph node disease, the NPV of a CMR was 91%, the PPV of equivocal uptake and a positive scan were 33% and 88%, respectively. Likelihood ratios for lymph node disease for CMR, equivocal and positive scans were 0.19, 0.97 and 15.1, respectively. CONCLUSION: Compared with the accuracy reported in the literature following chemoradiotherapy, response assessment FDG PET-CT following radical radiotherapy without chemotherapy had a similarly high NPV, whereas the PPV following a positive scan was higher.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Oncogene ; 35(41): 5446-5455, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27065322

RESUMO

Cell cycle genes are often aberrantly expressed in cancer, but how their misexpression drives tumorigenesis mostly remains unclear. From S phase to early mitosis, EMI1 (also known as FBXO5) inhibits the anaphase-promoting complex/cyclosome, which controls cell cycle progression through the sequential degradation of various substrates. By analyzing 7403 human tumor samples, we find that EMI1 overexpression is widespread in solid tumors but not in blood cancers. In solid cancers, EMI1 overexpression is a strong prognostic marker for poor patient outcome. To investigate causality, we generated a transgenic mouse model in which we overexpressed Emi1. Emi1-overexpressing animals develop a wide variety of solid tumors, in particular adenomas and carcinomas with inflammation and lymphocyte infiltration, but not blood cancers. These tumors are significantly larger and more penetrant, abundant, proliferative and metastatic than control tumors. In addition, they are highly aneuploid with tumor cells frequently being in early mitosis and showing mitotic abnormalities, including lagging and incorrectly segregating chromosomes. We further demonstrate in vitro that even though EMI1 overexpression may cause mitotic arrest and cell death, it also promotes chromosome instability (CIN) following delayed chromosome alignment and anaphase onset. In human solid tumors, EMI1 is co-expressed with many markers for CIN and EMI1 overexpression is a stronger marker for CIN than most well-established ones. The fact that Emi1 overexpression promotes CIN and the formation of solid cancers in vivo indicates that Emi1 overexpression actively drives solid tumorigenesis. These novel mechanistic insights have important clinical implications.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinogênese/genética , Proteínas de Ciclo Celular/biossíntese , Instabilidade Cromossômica/genética , Proteínas F-Box/biossíntese , Neoplasias/genética , Ciclossomo-Complexo Promotor de Anáfase/genética , Animais , Biomarcadores Tumorais/genética , Proteínas de Ciclo Celular/genética , Proteínas F-Box/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Transgênicos , Mitose/genética , Neoplasias/patologia , Fosforilação
9.
Clin Radiol ; 71(6): 501-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27005017

RESUMO

AIM: To analyse the positive rate for cancer on additional abdominopelvic computed tomography (CT) in patients with unprovoked venous thromboembolism (VTE), evaluate the subsequent emergence of a cancer diagnosis in the clinical follow-up period, and identify any possible predictive factors of cancer in this cohort, which may allow better selection of patients for additional imaging. MATERIALS AND METHODS: Consecutive adult patients with VTE were retrospectively identified in two large teaching hospitals between January 2013 and June 2014, including a subset of those with unprovoked VTE. Relevant demographic data were extracted and analysed. All patients had a minimum of 12 months clinicoradiological follow-up. RESULTS: One thousand four hundred and forty-six patients with VTE were deemed eligible, of which 699 (48%) were male; the median age (range) was 66 (16-102) years. The prevalence of pre-existing cancer in these patients was 343/1446 (24%), and 388/1446 (27%) were classified as unprovoked VTE. In 12/1446 (0.8%), cancer was diagnosed synchronously with VTE on the initial imaging investigation. Additional screening imaging was performed in 232/388 (60%) including abdominopelvic CT in 205 (53%) patients with unprovoked VTE. Only five additional cancers were identified, all of these occurring in patients with clinical symptoms suspicious for cancer. None of the additional CT examinations identified any clinically occult cancer in asymptomatic patients, and subsequent mean follow-up of 22 (SD=6) months also failed to reveal any further cancer diagnosis. CONCLUSION: Contrary to the National Institute of Health and Care Excellence (NICE) guidance, the yield of performing additional abdominopelvic CT as a screening tool for occult cancer in asymptomatic patients with unprovoked VTE is negligible. A more selective and clinically-driven assessment of these patients is recommended.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Tromboembolia Venosa/diagnóstico por imagem , Tromboembolia Venosa/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pelve/diagnóstico por imagem , Prognóstico , Radiografia Abdominal/métodos , Radiografia Abdominal/estatística & dados numéricos , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Reino Unido/epidemiologia , Adulto Jovem
10.
Clin Oncol (R Coll Radiol) ; 27(10): 588-600, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26133461

RESUMO

The identification of robust prognostic and predictive biomarkers would transform the ability to implement an individualised approach to radiotherapy. In this regard, there has been a surge of interest in the use of functional imaging to assess key underlying biological processes within tumours and their response to therapy. Importantly, functional imaging biomarkers hold the potential to evaluate tumour heterogeneity/biology both spatially and temporally. An ever-increasing range of functional imaging techniques is now available primarily involving positron emission tomography and magnetic resonance imaging. Small-scale studies across multiple tumour types have consistently been able to correlate changes in functional imaging parameters during radiotherapy with disease outcomes. Considerable challenges remain before the implementation of functional imaging biomarkers into routine clinical practice, including the inherent temporal variability of biological processes within tumours, reproducibility of imaging, determination of optimal imaging technique/combinations, timing during treatment and design of appropriate validation studies.


Assuntos
Biomarcadores Tumorais , Diagnóstico por Imagem/métodos , Neoplasias/radioterapia , Humanos , Neoplasias/metabolismo , Medicina de Precisão , Prognóstico
11.
Clin Radiol ; 70(7): 787-800, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25917543

RESUMO

Integrated positron emission tomography/computed tomography (PET/CT) with the glucose analogue, 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG), is an evolving hybrid imaging technique in the evaluation of an important and diverse group of pathological conditions, which are characterised by infection and aseptic inflammation. With a rapidly expanding body of evidence, it is being increasingly recognised that, in addition to its established role in oncological imaging, FDG PET/CT also has clinical utility in suspected infection and inflammation. The technique can identify the source of infection or inflammation in a timely fashion ahead of morphological changes on conventional anatomical imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), map the extent and severity of disease, identify sites for tissue sampling, and assess therapy response. FDG PET/CT exhibits distinct advantages over traditional radionuclide imaging techniques in terms of shorter duration of examination, higher spatial resolution, non-invasive nature of acquisition, ability to perform quantitative analyses, and the provision of a synergistic combination of functional and anatomical imaging. With the use of illustrative clinico-radiological cases, this article discusses the current and emerging evidence for the use of FDG PET/CT in a broad spectrum of disorders, such as fever of unknown origin, sarcoidosis, large vessel vasculitis, musculoskeletal infections, joint prosthesis or implant-related complications, human immunodeficiency virus (HIV)-related infections, and miscellaneous indications, such as IgG4-related systemic disease. It will also briefly summarise the role of more novel tracers such as FDG-labelled leukocytes and gallium-68 PET tracers in this arena.


Assuntos
Infecções/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Medicina Baseada em Evidências , Fluordesoxiglucose F18 , Humanos , Infecções/metabolismo , Inflamação/metabolismo , Guias de Prática Clínica como Assunto , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
12.
Eur Heart J Cardiovasc Imaging ; 15(3): 275-83, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23975570

RESUMO

AIMS: To study the prognostic value of rapid-acquisition adenosine stress-rest myocardial perfusion scintigraphy (MPS) on a gamma camera using multipinhole collimation and cadmium-zinc-telluride (CZT) detectors. The secondary aim was to assess the diagnostic accuracy of the technique compared with invasive coronary angiography. METHODS AND RESULTS: Retrospective analysis of 1109 consecutive patients undergoing MPS in a routine clinical setting on a high-efficiency multipinhole gamma camera. MPS acquisition, performed with a standard injection of 550 MBq of (99m)Tc-tetrofosmin, required a mean (±SD) scanning time of 322 ± 51 s. The hard cardiac event rate at a median (inter-quartile range) follow-up of 624 (552-699) days was 0.4% (95% CI 0.1-1.1) in patients with no significant perfusion abnormality versus 6.8% (95% CI 4.3-10.7%, P < 0.001) in those with an abnormal scan. In a sub-group of 165 patients, comparison with obstructive coronary artery disease on X-ray angiography gave a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for rapid-acquisition MPS of 84% (95% CI 74-91), 79% (95% CI 68-87), 82% (95% CI 72-89), 81% (95% CI 70-89), and 82% (95% CI 73-89), respectively. CONCLUSIONS: MPS performed on a CZT solid-state detector camera with multipinhole collimation is an evolutionary development that provides reliable prognostic and diagnostic information, while significantly reducing image acquisition time.


Assuntos
Cádmio , Tomografia Computadorizada por Emissão de Fóton Único de Sincronização Cardíaca/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Câmaras gama , Imagem de Perfusão do Miocárdio/instrumentação , Telúrio , Zinco , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomografia Computadorizada por Emissão de Fóton Único de Sincronização Cardíaca/instrumentação , Cardiologia/métodos , Estudos de Coortes , Angiografia Coronária/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
13.
Soft Matter ; 9(47)2013 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-24319491

RESUMO

The desire to synthesize soft supramolecular structures with size scales similar to biological systems has led to work in assembly of polymeric nanomaterials. Recent advances in the isolation of generationally homogenous poly(amidoamine) (PAMAM) dendrimer enables their use as quantized building blocks. Here, we report their assembly into precise nanoclusters. In this work, click-functional ligands are stochastically conjugated to monomeric generation 5 PAMAM dendrimer and separated via reverse-phase HPLC to isolate dendrimers with precise numbers of click ligands per dendrimer particle. The click-ligand/dendrimer conjugates are then employed as modular building blocks for the synthesis of defined nanostructures. Complimentary click chemistry employing dendrimers with 1, 2, 3, or 4 ring-strained cyclooctyne ligands and dendrimers with 1 azide ligand were utilized to prepare megamer structures containing 2 to 5 ~30,000 kDa monomer units as characterized by mass spectrometry, size exclusion chromatography, and reverse-phase liquid chromatography. The resulting structures are flexible with masses ranging from 60,000 to 150,000 kDa, and are soluble in water, methanol, and dimethylsulfoxide.

14.
Clin Exp Allergy ; 41(10): 1379-85, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21676042

RESUMO

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an interesting model to investigate the existence of a non-allergic unified airway. The factors associated with airway dysfunction in CRSwNP are not fully understood. OBJECTIVE: To assess the impact of nasal disease on lower airway dysfunction in CRSwNP. METHODS: Fifty-seven patients with CRSwNP underwent spirometry, nasal endoscopy, exhaled nitric oxide, methacholine bronchial challenge, blood sampling for total IgE, eosinophil count and radioallergosorbent testing (NCT00788749). Three phenotypic groups were identified: 'asthma group' (asthma diagnosis); 'inflammatory group' [no asthma diagnosis, but elevated fractionated exhaled nitric oxide (FE(NO)) and/or bronchial-hyperreactivity (BHR)]; and 'non-inflammatory group' (no asthma diagnosis, no BHR and normal FE(NO)). Group comparisons, univariate and multivariate analyses were performed to examine associations with airway dysfunction. RESULTS: FEV(1) and FEF(25-75%) were reduced in asthma, but there was no difference between the non-asthmatic groups. Total IgE and eosinophils were elevated in asthma vs. the non-inflammatory group, but there was no difference for asthma vs. inflammatory groups. BHR was the only significant predictor of FEV(1) (P<0.001). For FEF(25-75), BHR and eosinophil count were independent predictors (P<0.001 and P=0.04). Nasal outcomes were not predictors of spirometry. CONCLUSION AND CLINICAL RELEVANCE: In CRSwNP there is asymptomatic airway dysfunction suggestive of an asthmatic phenotype. Impairment of lung function is significantly associated with BHR and eosinophilia but not parameters of nasal disease suggesting that severity of airway dysfunction relates to the spectrum of asthma rather than rhinosinusitis. Lower airway dysfunction is common in CRSwNP but does not correlate to the severity of nasal disease. Signs and symptoms of asthma should be sought and treated in CRSwNP.


Assuntos
Asma/imunologia , Asma/fisiopatologia , Brônquios/fisiopatologia , Pólipos Nasais/fisiopatologia , Rinite/fisiopatologia , Sinusite/fisiopatologia , Adulto , Asma/diagnóstico , Hiper-Reatividade Brônquica/diagnóstico , Hiper-Reatividade Brônquica/patologia , Hiper-Reatividade Brônquica/fisiopatologia , Doença Crônica , Eosinófilos/imunologia , Eosinófilos/patologia , Expiração , Feminino , Humanos , Imunoglobulina E/sangue , Inflamação , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/patologia , Óxido Nítrico/análise , Testes de Função Respiratória , Rinite/complicações , Rinite/patologia , Sinusite/complicações , Sinusite/patologia
16.
Mol Biosyst ; 7(1): 101-15, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20714507

RESUMO

Miniaturisation is revolutionary to high-throughput proteomics. These technologies have gained much interest in the past decade, as they allow for sensitive parallel analysis of small amounts of biological materials. This review describes the state of the art of proteomics-on-chip, with a particular focus on the fundamental proteomics-on-chip challenges. The important role of bio-interfacial interactions and strategies to control them are presented. Various coating methodologies for on-chip protein/peptide separation are reviewed to provide an overview of the principles of protein-resistant and protein immobilisation coatings, and their effectiveness.


Assuntos
Proteômica/métodos
17.
Respir Med ; 105(4): 558-65, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21144723

RESUMO

INTRODUCTION: Current asthma guidelines recommend step-down of inhaled corticosteroids (ICS) to the minimum dose required for control of symptoms. AIM: To determine if supervised step-down of (ICS) in the community has any effect on asthmatic inflammation. METHODS: 119 Community based asthmatics underwent progressive step-down of therapy until they became unstable or reached an (ICS) dose of ≤200 µg beclomethasone dipropionate (BDP) or equivalent. Once unstable, participants stepped back up to the last stable dose of ICS. Exhaled nitric oxide (NO) and mannitol challenge were performed at the start and end of step-down. Asthma Quality of Life Questionnaire (AQLQ) and spirometry were recorded at each step-down visit. RESULTS: The median (interquartile range) BDP equivalent dose was significantly higher pre vs. post step-down: 400 µg (400-800) and 250 µg (200-400) per day respectively (P < 0.05). Examination of change in PD(10) in individual patients revealed that 34% had an improvement (>+1 dd), 47% had no change (±-1 dd), and 19% had a worsening (<-1 dd). The geometric mean fold ratio in NO for pre vs. post was 0.96 (95% CI 0.87 to 1.06, P = 0.43). Mean (SEM) values for FEV(1) were 86.2% (1.51) vs. 84.5% (1.46) (P = 0.04). There was a significant improvement in AQLQ. CONCLUSIONS: We have demonstrated that a significant reduction in ICS dose may be achieved in a community setting without any worsening of airways inflammation or lung function, and with an associated improvement quality of life in the majority of patients. This apparent disconnect may reflect enhanced adherence due to supervision of step-down.


Assuntos
Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Administração por Inalação , Asma/epidemiologia , Esquema de Medicação , Feminino , Humanos , Masculino , Manitol , Pessoa de Meia-Idade , Óxido Nítrico/análise , Guias de Prática Clínica como Assunto , Qualidade de Vida , Espirometria , Inquéritos e Questionários , Reino Unido
18.
Clin Exp Allergy ; 40(5): 731-7, 2010 05.
Artigo em Inglês | MEDLINE | ID: mdl-20214665

RESUMO

BACKGROUND: Elite swimmers have high rates of rhinoconjunctivitis and exercise-induced bronchoconstriction. Moreover, exposure to chlorine and chlorine metabolites is known to induce bronchial hyper-reactivity. OBJECTIVE: To assess the early and late effects of chlorine and exercise on the unified airway of elite swimmers, and to compare the response to mannitol and field-based exercise challenge. METHODS: The Scottish national squad underwent exhaled tidal (FE(NO)) and nasal (N(NO)) nitric oxide measurement, peak nasal inspiratory flow (PNIF), and forced expiratory volume in 1 s before, immediately after, and 4-6 h post-swimming. A sport-specific exercise test was carried out during an intensive lactate set (8 min at >/=80% maximum hear rate). All swimmers underwent mannitol challenge, and completed a health questionnaire. RESULTS: N=61 swimmers were assessed: 8/59 (14%) of swimmers had a positive mannitol challenge. Nine out of 57 (16%) of swimmers had a positive exercise test. Only one swimmer was positive to both. Swimmers with a positive mannitol had a significantly higher baseline FE(NO) (37.3 vs. 18.0 p.p.b., P=0.03) than those with a positive exercise challenge. A significant decrease in FE(NO) was observed pre vs. immediate and delayed post-chlorine exposure: mean (95% CI) 18.7 (15.9-22.0) p.p.b. vs. 15.9 (13.3-19.1) p.p.b. (P<0.01), and 13.9 (11.5-16.7) p.p.b. (P<0.01), respectively. There were no significant differences in N(NO.) Mean PNIF increased from 142.4 L/min (5.8) at baseline to 162.6 L/min (6.3) immediately post-exposure (P<0.01). Delayed post-exposure PNIF was not significantly different from pre-exposure. CONCLUSIONS: No association was found between mannitol and standardized field-based testing in elite swimmers. Mannitol was associated with a high baseline FE(NO); however, exercise/chlorine challenge was not. Thus, mannitol may identify swimmers with a 'traditional' inflammatory asthmatic phenotype, while field-based exercise/chlorine challenge may identify a swimmer-specific bronchoconstrictor response. A sustained fall in FE(NO) following chlorine exposure suggests that a non-cellular, perhaps neurogenic, response may be involved in this group of athletes.


Assuntos
Asma Induzida por Exercício/etiologia , Testes de Provocação Brônquica/métodos , Cloro/efeitos adversos , Manitol , Natação , Adolescente , Asma Induzida por Exercício/diagnóstico , Teste de Esforço , Humanos , Óxido Nítrico/análise , Escócia , Sensibilidade e Especificidade , Fatores de Tempo
19.
Allergy ; 65(2): 269-73, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19793061

RESUMO

BACKGROUND: Chlorine metabolites and high training load may produce exercise-induced bronchospasm (EIB) in elite swimmers. The aim of this study was to assess the combined effects of chlorine and exercise on the unified airway of adolescent elite swimmers. METHODS: The Scottish Midlands District squad were assessed during an indoor pool session at the National Swimming Academy. Athletes trained at least 8 h per week. Subjects underwent tidal (T(NO)) and nasal (N(NO)) exhaled NO and peak nasal inspiratory flow (PNIF) pre and post a 2 h session. A physiological exercise challenge assessed EIB in n = 36 swimmers (>10% fall in forced expiratory volume in 1 s (FEV(1))). RESULTS: Combined and free chlorine levels (mg/l) were 1.66 and 0.3 respectively. n = 36 swimmers (mean age 13.3 years) were assessed: n = 8 (22%) had known asthma; n = 13 (36%) had a positive physiological challenge; 18 (50%) complained of symptoms suggestive of EIB. n = 10/28 (36%) who did not have asthma were found to have a positive exercise challenge. There was no significant association between reported exercise symptoms and positive exercise test. There was no significant change in T(NO) or N(NO) for pre vs postexposure, irrespective of asthma diagnosis or AHR. n = 15 (42%) swimmers complained of worsening nasal symptoms postexposure, but only n = 7 (14%) had a demonstrable fall in PNIF (mean 33 l/min). No significant association was found between PNIF and symptoms. CONCLUSIONS: Combined exposure to chlorine and exercise did not affect surrogate markers of inflammation in the unified airway. There was a high prevalence of undiagnosed EIB.


Assuntos
Asma Induzida por Exercício/epidemiologia , Atletas , Cloro/efeitos adversos , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/fisiopatologia , Natação , Adolescente , Asma Induzida por Exercício/etiologia , Criança , Feminino , Humanos , Masculino , Espirometria , Adulto Jovem
20.
Allergy ; 65(3): 359-67, 2010 03.
Artigo em Inglês | MEDLINE | ID: mdl-19804441

RESUMO

BACKGROUND: Treating allergic rhinitis may have a downstream anti-inflammatory effect on the lower airways. We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid. METHODS: Twenty five participants were randomized to receive two weeks of 100 microg/day (Low dose) or 500 microg/day (High dose) of inhaled fluticasone propionate both with intranasal placebo; or inhaled fluticasone 100 microg/day with intranasal fluticasone 200 microg/day (Combined) in a double-blind cross-over fashion. RESULTS: Low dose fluticasone produced a shift of 1.20 doubling-dilutions (95% CI, 0.63, 1.77); Combined fluticasone, 1.79 doubling-dilutions (95% CI, 0.77, 2.80) and high dose fluticasone, 2.01 doubling-dilutions (95% CI, 1.42, 2.61) in methacholine PC(20) from respective baselines. There was a significant difference between high and low doses: 0.82 doubling dilutions (95%CI, 0.12, 1.50) but not between combined and low dose 0.58 doubling dilutions (95% CI, -0.78, 1.95). Combined treatment alone produced improvements in peak nasal inspiratory flow (P < 0.001), rhinitis quality of life (P = 0.004) and nasal NO (P = 0.01); reduced blood eosinophil count (P = 0.03), and serum eosinophil cationic protein (P = 0.02). All treatments significantly improved tidal NO, FEV(1) and asthma quality of life. CONCLUSIONS: High-dose fluticasone was superior to low dose fluticasone for methacholine PC20, demonstrating room for further improvement. Combined treatment was not significantly different from low dose fluticasone and we could not demonstrate a steroid sparing effect on methacholine PC20. Combined treatment alone produced improvements in upper airway outcomes and suppressed systemic inflammation but not adrenal function.


Assuntos
Corticosteroides/administração & dosagem , Androstadienos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Rinite Alérgica Perene/tratamento farmacológico , Administração por Inalação , Administração Intranasal , Adulto , Testes Respiratórios , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Fluticasona , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Função Respiratória , Adulto Jovem
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