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1.
Chest ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32184111

RESUMO

BACKGROUND: and Research Question: Chitinase activity is an important innate immune defence mechanism against infection including fungi. The two human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are associated to allergy, asthma and chronic obstructive pulmonary disease (COPD), however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown STUDY DESIGN AND METHODS: A prospective cohort of n=463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia and Scotland) including non-diseased (n=35), severe asthma (n=54), COPD (n=90), bronchiectasis (n=241) and BCO (n=43). Systemic Chitinase levels were assessed, and, for bronchiectasis and BCO related to clinical outcomes, airway Aspergillus status and underlying pulmonary mycobiome profiles RESULTS: Systemic chitinase activity is significantly elevated in bronchiectasis and BCO exceeding that in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (>3 exacerbations/year). Subgroup analysis reveals an association between CHIT1 activity and the 'frequent exacerbator' phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa including Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asians with high CHIT1 may have potential roles in bronchiectasis exacerbations INTERPRETATION: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven 'frequent exacerbators' with bronchiectasis in South-East Asian populations.

2.
Ir J Med Sci ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31721041

RESUMO

BACKGROUND: Subjects with severe obesity (BMI > 40 kg/m2) have worse physical function and sleep less than lean people (BMI 18.5-25 kg/m2). METHODS: In 554 subjects with severe obesity, we compared physical function in those with normal sleep duration (NSD, 6-9 h/night), short sleep duration (SSD, ≤ 6 h/night) and long sleep duration (LSD, ≥ 9 h/night). RESULTS: The mean (±SD) age and BMI were 43.1 (± 11.1) years and 50.9 ± 8.6 kg/m2 respectively. One hundred ninety-six (35.4%) were male. More subjects in the NSD group (n = 256) were able to ascend and descend a step 50 times than in the SSD group (n = 247) or the LSD group (n = 51, 75.5% vs 62.8% vs 56.9%, p = 0.002). A similar observation was made for step speed (0.45 ± 0.11 vs 0.43 ± 0.10 vs 0.40 ± 0.11 steps/s respectively, p = 0.001). NSD participants were less likely to have fallen in the preceding year compared to LSD participants (21.1% vs 39.2%, p = 0.007) and also reported less low back pain compared to SSD participants (60.8% vs 75.9%, p = 0.004). CONCLUSIONS: In conclusion, abnormal sleep duration is associated with reduced physical function in non-elderly severely obese subjects. The effects of sleep hygiene interventions in this cohort warrant further assessment and may be beneficial to their physical function.

3.
Asian Pac J Cancer Prev ; 20(7): 1959-1965, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350951

RESUMO

Objective: Epidemiological studies have reported the close relationship between risk for lung cancers and air pollution in particular, for non-smoking related lung cancers. However, most studies used residential address as proxies which may not estimate accurately an individual's air pollution exposure. Therefore, the aim of this study was to identify risk factors such as occupation and mode of transportation associated with lung cancer diagnosis and death. Methods: Subjects with lung cancer (n=514) were evaluated both by chart reviews for clinical data and interviews to determine residential address for ten years, main occupation and main mode of transportation. Annual particulate matter with diameter size less than 2.5 micrometre (PM2.5) concentration were calculated based on particulate matter with diameter size less than 10 micrometre (PM10) data recorded by Malaysian Department of Environment. Logistic regression analysis, cluster analysis and the Cox regression analysis were performed to the studied variables. Results: This study concurred with previous studies that lung adenocarcinoma were diagnosed in predominantly younger, female non-smokers compared to the other types of lung cancers. Lung adenocarcinoma subjects had annual PM2.5 that was almost twice higher than squamous cell carcinoma, small cell carcinoma and other histological subtypes (p=0.024). Independent of smoking, the κ -means cluster analysis revealed two clusters in which the high risk cluster involves occupation risk with air pollution of more than four hours per day, main transportation involving motorcycle and trucks and mean annual PM2.5 concentration of more than 30 based on residential address for more than ten years. The increased risk for the high-risk cluster was more than five times for the diagnosis of lung adenocarcinoma (OR=5.69, 95% CI=3.14-7.21, p<0.001). The hazard ratio for the high-risk cluster was 3.89 (95% CI=2.12-4.56, p=0.02) for lung adenocarcinoma mortality at 1 year. Conclusion: High-risk cluster including PM2.5, occupation risk and mode of transportation as surrogates for air-pollution exposure was identified and highly associated with lung adenocarcinoma diagnosis and 1-year mortality.


Assuntos
Adenocarcinoma de Pulmão/mortalidade , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/mortalidade , Exposição Ocupacional/efeitos adversos , Material Particulado/efeitos adversos , Transportes/estatística & dados numéricos , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/etiologia , Idoso , Análise por Conglomerados , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Fatores de Tempo
4.
Am J Respir Crit Care Med ; 199(7): 842-853, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30265843

RESUMO

RATIONALE: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non-cystic fibrosis bronchiectasis remain unclear. OBJECTIVES: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. METHODS: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined. MEASUREMENTS AND MAIN RESULTS: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. CONCLUSIONS: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.


Assuntos
Alérgenos/efeitos adversos , Alérgenos/imunologia , Aspergillus , Asma/etiologia , Asma/imunologia , Bronquiectasia/complicações , Bronquiectasia/imunologia , Pyroglyphidae , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Coortes , Feminino , Humanos , Hipersensibilidade/imunologia , Imunização , Masculino , Pessoa de Meia-Idade
5.
Eurasian J Med ; 50(2): 122-124, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30002580

RESUMO

Suture granuloma rarely occurs after thyroid surgery using non-absorbable sutures. We report the case of a 63-year-old female with a chronic discharging sinus in the anterior neck region. She had a history of subtotal thyroidectomy at the age of 45. The sinus had been excised and was reported as granulomatous lesions suggestive of tuberculosis. She was treated with anti-tuberculous medications, but unfortunately, she developed side effects. Histopathological slides were re-evaluated, which showed evidence of foreign material under polarized light; hence, the diagnosis was revised to suture granuloma. In conclusion, although sinus tract discharges are commonly attributed to tuberculosis, physicians should consider suture granuloma if they encounter a patient who has undergone a surgical procedure in the past.

6.
Respirology ; 23(10): 914-920, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29923364

RESUMO

BACKGROUND AND OBJECTIVE: The Southeast Asia (SEA) haze is an annual problem and at its worst could produce respirable particles of concentrations up to 500 µg/m3 which is five times the level considered as 'unhealthy'. However, there are limited reports examining the direct clinical impact of the annual haze. This study examines the effects of the SEA haze on respiratory admissions. METHODS: Data from all respiratory admissions in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from 1st January 2014 to 31st December 2015 were collected retrospectively from chart and electronic database. A total of 16 weeks of haze period had been formally dated by the Department of Environment using the definition of weather phenomenon leading to atmospheric visibility of less than 10 km. Multivariable regression analyses were performed to estimate rate ratios and 95% CI. RESULTS: There were 1968 subjects admitted for respiratory admissions in UKMMC during the study period. Incidence rates per week were significantly different between the two groups with 27.6 ± 9.2 cases per week during the haze versus 15.7 ± 6.7 cases per week during the non-haze period (P < 0.01). A total of 4% versus 2% was admitted to the intensive care unit in the haze and the non-haze groups, respectively (P = 0.02). The mean ± SD lengths of stay was 12.1 ± 5.2 days; the haze group had a longer stay (18.2 ± 9.7 days) compared to the non-haze groups (9.7 ± 3.9) (P < 0.001). CONCLUSION: The annual SEA haze is associated with increased respiratory admissions.


Assuntos
Poluição do Ar , Material Particulado , Admissão do Paciente/estatística & dados numéricos , Doenças Respiratórias/epidemiologia , Centros Médicos Acadêmicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Tempo de Internação , Malásia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano
7.
Eur Respir J ; 52(1)2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29880655

RESUMO

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a "research priorities" consensus statement for bronchiectasis.Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S-28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes.The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and ClavisporaAspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations.The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.


Assuntos
Bronquiectasia/complicações , Fungos/classificação , Micobioma , Aspergilose Pulmonar/complicações , Adulto , Idoso , Anticorpos Antifúngicos/sangue , Aspergillus , Bronquiectasia/imunologia , Bronquiectasia/microbiologia , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , Malásia , Masculino , Pessoa de Meia-Idade , Aspergilose Pulmonar/imunologia , Singapura , Escarro/microbiologia , Reino Unido
8.
Respirology ; 23(12): 1173-1179, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29790229

RESUMO

BACKGROUND AND OBJECTIVE: Although the multi-ethnic European Respiratory Society/Global Lung Initiative (ERS/GLI) 2012 reference values have been developed, the Taskforce has called for further validation specifically on subpopulations that were under represented such as the Malays, Chinese and Indians, in which the two latter ethnic groups represent about one-third of the world population. Thus, the aims of this study were to evaluate the appropriateness of the ERS/GLI 2012 reference values in a healthy adult Malaysian population and to construct a local lung function reference for the Malaysia population specific to the three major ethnic groups. METHODS: Acceptable spirometry data were obtained from 30 281 healthy subjects aged 35-70 years comprising Malays, Chinese and Indians from the Malaysian Cohort. Local reference values were calculated using regression analysis and evaluated using ERS/GLI reference values to obtain GLI Z-scores. RESULTS: The mean (SD) of the forced expiratory volume in 1 s (FEV1 ) for males were 2.67 (0.46), 2.89 (0.48) and 2.60 (0.46) and females were 1.91 (0.36), 2.13 (0.37) and 1.86 (0.35) for Malays, Chinese and Indians, respectively. For forced vital capacity (FVC), the mean (SD) for males were 3.03 (0.53), 3.28 (0.58) and 2.92 (0.53) and females were 2.15 (0.40), 2.38 (0.43) and 2.07 (0.41) for Malays, Chinese and Indians, respectively. The mean GLI Z-scores were less than -0.5 for FEV1 and FVC and more than 0.5 for FEV1 /FVC. A large percentage of subjects in all the three ethnic groups were defined lower than the lower limit of normal. CONCLUSION: This present and large multi-ethnic Asian-based study demonstrates clinically significant deviation from ERS/GLI 2012 equations for spirometry. It highlights the importance of validating predicted equations for spirometry in local populations.


Assuntos
Pulmão/fisiologia , Espirometria , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Coortes , Grupos Étnicos , Feminino , Voluntários Saudáveis , Humanos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Espirometria/métodos , Espirometria/normas
9.
Lung Cancer ; 118: 69-75, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29572006

RESUMO

Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Sistema Respiratório/patologia , Poluição do Ar , Carcinogênese , Dano ao DNA , Exposição Ambiental/efeitos adversos , Epigenômica , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Óxidos de Nitrogênio , Material Particulado , Fatores de Risco , Safrol/análogos & derivados
10.
Respirol Case Rep ; 6(2): e00293, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29321937

RESUMO

The use of Cannabis sativa, also known as marijuana, is believed to have dated back to thousands of years B.C. More than 200 decades later, it remains a popular recreational psychoactive substance that can be smoked through a water pipe. We report a case of marijuana smoking via a "bong" device, which has resulted in severe Pseudomonas aeruginosa necrotizing pneumonia treated with conservative medical therapy. This case highlights the importance of recognizing that life-threatening pneumonia can potentially be linked to marijuana and "bong" usage. Complicated cases should be considered for early surgical intervention.

11.
Tob Induc Dis ; 16: 57, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31516454

RESUMO

INTRODUCTION: E-cigarette use is an emerging phenomenon with increasing recognition and acceptance globally. This study aims to create a profile of e-cigarette users among university students in Malaysia. METHODS: The study was conducted using a cross-sectional research involving six universities in Malaysia. A semi-structured questionnaire was distributed to 1302 randomly selected students, who either smoked cigarettes and/or e-cigarettes. The 2011 version of Global Adult Tobacco Surveys (GATS) tool was used to record the respondents' sociodemographic data. RESULTS: The study revealed that 74.9% of the respondents smoked e-cigarettes; 40.3% used both cigarettes and e-cigarettes (dual users), and 34.5% were exclusive e-cigarette users. The exclusive use of e-cigarettes was related to gender (OR=0.18, 95% CI: 0.09-0.39). Also, male respondents were the majority users (95%). Of the respondents, 75.2 % were Malays, 98.0% single and most believed they have no health problems (92.1%). Further findings revealed the occurrence of adverse effects, dizziness 14.4%, cough 14.1%, and headaches 12.4%. Overall, 57.8% of the respondents used e-cigarettes as a smoking cessation tool, while others consider e-cigarettes a self-image enhancing tool or as part of social activities. CONCLUSIONS: Further research on the use of e-cigarettes should be conducted on a large number of respondents in other settings to augment the findings of this study, and also guide policy making on and prevention practice of e-cigarette use, among the general student population in Malaysia.

12.
PLoS One ; 12(12): e0189846, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29267317

RESUMO

BACKGROUND: Malignant solitary pulmonary nodules (SPN) have become more prevalent, with upper lobes predilection. Probe-based confocal laser endomicroscopy (pCLE) provides in-vivo imaging of SPN. However, the stiffness of the 1mm confocal probe (AlveoFlex) causes difficult accessibility to the upper lobes. A thinner 600µm probe designed for bile duct exploration (CholangioFlex) has the potential to reach the upper lobes. OBJECTIVES: To examine the accessibility of malignant SPNs in all segments of the lungs using either the 0.6mm or 1.4 mm probe and to assess the quality and inter observer interpretation of SPN confocal imaging obtained from either miniprobes. METHODS: Radial(r)-EBUS was used to locate and sample the SPN. In-vivo pCLE analysis of the SPN was performed using either CholangioFlex (apical and posterior segments of the upper lobes) or AlveoFlex (other segments) introduced into the guide sheath before sampling. pCLE features were compared between the two probes. RESULTS: Fourty-eight patients with malignant SPN were included (NCT01931579). The diagnostic accuracy for lung cancer using r-EBUS coupled with pCLE imaging was 79.2%. All the SPNs were successfully explored with either one of the probes (19 and 29 subjects for CholangioFlex and AlveoFlex, respectively). A specific solid pattern in the SPN was found in 30 pCLE explorations. Comparison between the two probes found no differences in the axial fibers thickness, cell size and specific solid pattern in the nodules. Extra-alveolar microvessel size appeared larger using CholangioFlex suggesting less compression effect. The kappa test for interobserver agreement for the identification of solid pattern was 0.74 (p = 0.001). CONCLUSION: This study demonstrates that pCLE imaging of SPNs is achievable in all segments of both lungs using either the 0.6mm or 1.4mm miniprobe.


Assuntos
Microscopia Confocal/métodos , Nódulo Pulmonar Solitário/patologia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Microscopia Confocal/instrumentação , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Alvéolos Pulmonares/patologia
13.
BMJ Case Rep ; 20172017 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-29103009

RESUMO

A middle-aged woman with recurrent malignant melanoma presented initially with massive left pleural effusion. There was a complete obliteration of the left main bronchus on flexible bronchoscopy caused by a mass. Serial cryo-debulking of the tumour was done under rigid bronchoscopy; however, the outcome was not favourable due to the aggressive tumour growth. Vemurafenib was planned after thoracic radiation. She was not keen for the biologics treatment due to financial constraints. We report a case of central airway obstruction due to recurrent aggressive melanoma. More evaluations are needed on the role of interventional pulmonologist for bronchoscopic debulking of this rapidly growing tumour as well as the role of biological agents in treating such cases.


Assuntos
Neoplasias Brônquicas/diagnóstico , Melanoma/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Cutâneas/diagnóstico , Obstrução das Vias Respiratórias/etiologia , Neoplasias Brônquicas/complicações , Neoplasias Brônquicas/secundário , Neoplasias Brônquicas/cirurgia , Broncoscopia , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Perna (Membro) , Melanoma/complicações , Melanoma/secundário , Melanoma/cirurgia , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Derrame Pleural/etiologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Tomografia Computadorizada por Raios X
14.
Sci Rep ; 7(1): 13803, 2017 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-29062067

RESUMO

Alpha-1 antitrypsin (AAT) augmentation therapy involves infusion of plasma-purified AAT to AAT deficient individuals. Whether treatment affects microRNA expression has not been investigated. This study's objectives were to evaluate the effect of AAT augmentation therapy on altered miRNA expression in monocytes and investigate the mechanism. Monocytes were isolated from non-AAT deficient (MM) and AAT deficient (ZZ) individuals, and ZZs receiving AAT. mRNA (qRT-PCR, microarray), miRNA (miRNA profiling, qRT-PCR), and protein (western blotting) analyses were performed. Twenty one miRNAs were differentially expressed 3-fold between ZZs and MMs. miRNA validation studies demonstrated that in ZZ monocytes receiving AAT levels of miR-199a-5p, miR-598 and miR-320a, which are predicted to be regulated by NFκB, were restored to levels similar to MMs. Validated targets co-regulated by these miRNAs were reciprocally increased in ZZs receiving AAT in vivo and in vitro. Expression of these miRNAs could be increased in ZZ monocytes treated ex vivo with an NFκB agonist and decreased by NFκB inhibition. p50 and p65 mRNA and protein were significantly lower in ZZs receiving AAT than untreated ZZs. AAT augmentation therapy inhibits NFκB and decreases miR-199a-5p, miR-598 and miR-320a in ZZ monocytes. These NFκB-inhibitory properties may contribute to the anti-inflammatory effects of AAT augmentation therapy.


Assuntos
MicroRNAs/genética , Monócitos/metabolismo , NF-kappa B/antagonistas & inibidores , Inibidores da Tripsina/uso terapêutico , Deficiência de alfa 1-Antitripsina/genética , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Inibidores de Serino Proteinase , Deficiência de alfa 1-Antitripsina/tratamento farmacológico , Deficiência de alfa 1-Antitripsina/metabolismo
15.
BMJ Case Rep ; 20172017 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-28893806

RESUMO

This case series reviews two cases of elderly patients who presented with fever, cough and shortness of breath. Clinical examinations and initial chest radiographs confirmed unilateral pleural effusion. Thoracenteses were consistent with exudative pleural effusion. We commenced intravenous antibiotics treating for parapneumonic effusions. The first case showed persistent effusion despite drainage, and the second case had a little aspirate from pleural tapping. Subsequent ultrasound of the thorax showed multiloculated effusions. We made the decisions for intrapleural fibrinolytic therapy using low-dose alteplase 2.5 mg each time, in view of the elderly patient as sacrosanct for risk of bleeding. Furthermore, DNase was not used, as it is not yet available in our setting. Both of our patients had good clinical and radiological outcomes, without the need for surgical interventions.


Assuntos
Derrame Pleural/diagnóstico por imagem , Derrame Pleural/tratamento farmacológico , Toracentese/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Desoxirribonucleases , Diagnóstico Diferencial , Drenagem/métodos , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Derrame Pleural/microbiologia , Derrame Pleural/patologia , Radiografia/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Ultrassonografia/métodos
16.
BMC Pulm Med ; 16(1): 131, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27604085

RESUMO

BACKGROUND: Dental laboratory technicians are at risk of developing occupational respiratory diseases due to exposure to various potentially toxic substances in their working environment. Since 1939, few cases of silicosis among dental technician have been reported. CASE PRESENTATION: We illustrate a 38 year-old female, who worked in a dental laboratory for 20 years, initially treated as pulmonary tuberculosis and chronic necrotising aspergillosis without much improvement. Computed tomography guided lung biopsy and bronchoscopic transbronchial lung biopsy were performed. Lung tissue biopsies showed presence of refractile dental materials within the areas of histiocyte proliferation. The diagnosis of dental technician pneumoconiosis was obtained and our patient underwent pulmonary rehabilitation. CONCLUSIONS: This case highlights the importance of obtaining a detailed occupational history in tuberculosis endemic area, as pulmonary tuberculosis is a great mimicker of other respiratory diseases.


Assuntos
Técnicos em Prótese Dentária , Doenças Profissionais/diagnóstico por imagem , Pneumoconiose/diagnóstico por imagem , Adulto , Broncoscopia , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Radiografia Torácica , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico
17.
BMC Pulm Med ; 16(1): 53, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27080697

RESUMO

BACKGROUND: Tracheobronchial stenosis is a known complication of endobronchial tuberculosis. Despite antituberculous and steroid therapy, the development of bronchial stenosis is usually irreversible and requires airway patency to be restored by either bronchoscopic or surgical interventions. We report the use of balloon dilatation and topical mitomycin-C to successful restore airway patency. CASE PRESENTATION: We present a 24-year old lady with previous pulmonary tuberculosis and laryngeal tuberculosis in 2007 and 2013 respectively who presented with worsening dyspnoea and stridor. She had total left lung collapse with stenosis of both the upper trachea and left main bronchus. She underwent successful bronchoscopic balloon and manual rigid tube dilatation with topical mitomycin-C application over the stenotic tracheal segment. A second bronchoscopic intervention was performed after 20 weeks for the left main bronchus stenosis with serial balloon dilatation and topical mitomycin-C application. These interventions led to significant clinical and radiographic improvements. CONCLUSION: This case highlights that balloon dilatation and topical mitomycin-C application should be considered in selected patients with tracheobronchial stenosis following endobronchial tuberculosis, avoiding airway stenting and invasive surgical intervention.


Assuntos
Brônquios/diagnóstico por imagem , Broncopatias/complicações , Broncoscopia/métodos , Dilatação/métodos , Mitomicina/administração & dosagem , Estenose Traqueal/etiologia , Tuberculose/complicações , Administração Tópica , Brônquios/microbiologia , Broncopatias/diagnóstico , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Constrição Patológica/terapia , Feminino , Humanos , Inibidores da Síntese de Ácido Nucleico/administração & dosagem , Tomografia Computadorizada por Raios X , Estenose Traqueal/diagnóstico , Estenose Traqueal/terapia , Tuberculose/diagnóstico , Adulto Jovem
18.
Methods Mol Biol ; 1218: 365-73, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25319664

RESUMO

Several experimental methods exist to explore the microRNA (miRNA) regulome. These methods almost exclusively focus on multiple targets bound to a single, or perhaps a few miRNAs of interest. Here, we describe a microRNA capture affinity technology (miR-CATCH) which uses an affinity capture oligonucleotide to co-purify a single target messenger RNA (mRNA) together with all its endogenously bound miRNAs. This bench-top method is similar to RNA immunoprecipitation (RIP) and provides an experimental alternative to computational miRNA target prediction.


Assuntos
MicroRNAs/isolamento & purificação , Hibridização de Ácido Nucleico/métodos , RNA Mensageiro/isolamento & purificação , Pareamento de Bases , Sequência de Bases , Linhagem Celular , Humanos , MicroRNAs/química , MicroRNAs/genética , Dados de Sequência Molecular , Oligonucleotídeos Antissenso/síntese química , Oligonucleotídeos Antissenso/genética , RNA Mensageiro/química , RNA Mensageiro/genética
19.
Respir Med ; 108(10): 1409-23, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25240764

RESUMO

Asthma is a chronic inflammatory airway disease involving complex interplay between resident and infiltrative cells, which in turn are regulated by a wide range of host mediators. Identifying useful biomarkers correlating with clinical symptoms and degree of airway obstruction remain important to effective future asthma treatments. Transforming growth factor ß (TGF-ß) is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodeling within the asthmatic lung. Its role however, as a therapeutic target remains controversial. The aim of this review is to highlight its role in severe asthma including interactions with adaptive T-helper cells, cytokines and differentiation through regulatory T-cells. Associations between TGF-ß and eosinophils will be addressed and the effects of genetic polymorphisms of the TGF-ß1 gene explored in the context of asthma. We highlight TGF-ß1 as a potential future therapeutic target in severe asthma including its importance in identifying emerging clinical phenotypes in asthmatic subjects who may be suitable for individualized therapy through TGF-ß modulation.


Assuntos
Asma/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Asma/genética , Citocinas/metabolismo , Eosinófilos/metabolismo , Humanos , Polimorfismo Genético , Linfócitos T Reguladores/metabolismo , Células Th2/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
20.
BMC Immunol ; 15: 20, 2014 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-24884372

RESUMO

BACKGROUND: Antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may present with pulmonary involvement ranging from mild to life-threatening disease such as diffuse alveolar hemorrhage. There is a paucity of information regarding morbidity outcomes for AAV subjects presenting with lung involvement. This study determines the relationship between disease activity and damage in these subjects using the Birmingham Vasculitis Activity Score v 3 (BVAS 3) and Vasculitis Damage Index (VDI) respectively. RESULTS: 151 patients with AAV were included with 59 presenting initially with pulmonary involvement. The initial BVAS scores recorded at time of diagnosis were positively correlated with the final VDI scores at 24 months (p < 0.0001, rs = 0.5871). No differences between BVAS and VDI scores were seen for both groups, however in the lung-involvement group only, BVAS scores were significantly higher at 6, 12 and 24 months whilst the VDI scores were significantly higher at 12 and 24 months. Subjects presenting with pulmonary involvement had an increased likelihood for cardiovascular (OR 1.31, 95% CI 0.89, 1.54; p = 0.032) and renal (OR 1.32, 95% CI 1.22, 1.39; p = 0.005) involvement. Subjects presenting with lung involvement with granulomatosis with polyangiitis and microscopic polyangiitis had 24-month VDI scores that were significantly higher (p = 0.027, p = 0.045), and more likely to develop pulmonary fibrosis (OR 1.79, 95% CI 1.48, 2.12; p < 0.001). CONCLUSION: AAV subjects with lung involvement at presentation had a higher disease activity and damage scores at 6, 12 and 24 months follow-up representing a considerable burden of disease despite improvement in overall survival due to the introduction of immunosuppressive therapy.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Pulmão/imunologia , Pulmão/patologia , Vasculite/imunologia , Vasculite/patologia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Índice de Gravidade de Doença , Fatores de Tempo , Vasculite/diagnóstico
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