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ABSTRACT: Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.
European Respiratory Journal 06/2011; 39(3):677-84. · 5.89 Impact Factor
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ABSTRACT: To investigate whether adding moxifloxacin (MXF) to the standard anti-tuberculosis regimen can shorten the time to sputum culture conversion in pulmonary tuberculosis (PTB).
Adults with culture-positive PTB were divided into two treatment groups by their choice: standard regimen alone (HERZ group) and standard regimen plus daily 400 mg MXF in the first 2 months (MXF group). Sputum samples were collected thrice weekly in the first 8 weeks. The propensity score was calculated to estimate the conditional probability of entering the MXF group. Factors influencing time to culture conversion were investigated using Cox proportional hazards regression analysis stratified by propensity score.
Sixty-two patients were enrolled in the MXF group and 88 in the HERZ group; respectively 51 and 72 completed the study. The regimen was modified before culture conversion in respectively 6 (12%) and 12 (16%; P = 0.47) patients, due to adverse effects. The time to culture conversion was shorter in the MXF group (HR 2.1, 95%CI 1.4-3.2). The culture conversion rate after 6 weeks of treatment was respectively 82% and 61% (P = 0.011, <0.05/4, calculated using the modified Bonferroni method).
Adding MXF to the standard anti-tuberculosis regimen in the first 2 months was associated with a shorter time to culture conversion, a higher 6-week culture conversion rate and reduced transmission of tuberculosis.
The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 01/2010; 14(1):65-71. · 2.73 Impact Factor
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ABSTRACT: Patients presenting with pleural effusion of undetermined aetiology were prospectively enrolled, and an enzyme-linked immunospot (ELISPOT) assay on pleural fluid and peripheral blood was performed. Forty patients were studied, including 19 with culture- or biopsy-confirmed (n = 15) or clinically compatible (n = 4) tuberculous pleurisy, and 21 with pleural effusions due to non-tuberculous causes. The sensitivity, specificity and positive and negative predictive values of the assay were 94.7%, 85.7%, 85.7% and 94.7%, respectively, on pleural fluid, and 77.8%, 90.5%, 87.5% and 82.6%, respectively, on blood. Antigen-specific, interferon-gamma-secreting T-cells were concentrated eight to ten times in pleural fluid as compared with blood. Among the seven patients not suitable for pleural biopsy and three patients whose biopsy results were non-diagnostic, nine had positive ELISPOT result with pleural fluid. The ELISPOT assay for interferon-gamma can accurately diagnose tuberculous pleurisy and is helpful for patients not suitable for pleural biopsy and those whose biopsy results are non-diagnostic.
Clinical Microbiology and Infection 02/2009; 15(2):173-9. · 4.54 Impact Factor
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M.F. Guill,
R.H. Buckley,
W. Rocha,
J.P. Kemp,
A.T. Sega,
L.R. Shirley,
D.G. Tinkelman,
Z. Shaath-Schwen,
K.K. Dietrich,
L.J. Wille, T.H. Tsai
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ABSTRACT: Children, aged 6 to 12 years, with fall-pollenosis symptoms, were evaluated for their response to a new antihistamine, terfenadine, in a multicenter (six centers) I-week, double-blind, placebo controlled trial. All had positive skin tests to grass/weed pollens and/or mold spores prevalent in the fall at each center. Patients were administered placebo or terfenadine as suspension on a randomized basis, with children weighing <30 kg receiving terfenadine suspension, 30 mg twice daily, and those weighing >30 kg receiving 60 mg, twice daily. Of the 119 children enrolled. 79 received terfenadine and 40 received placebo. All but two (lost to follow-up) were included for the evaluation of drug safety, whereas 16 were excluded from the efficacy evaluation (11 receiving terfenadine and five receiving placebo) because of protocol noncompliance. Overall, varying degrees of control of symptoms were observed in 85% of the patients in the group taking terfenadine as compared to 60% in the group taking placebo. The symptoms of rhinorrhea, nasal congestion, and sneezing demonstrated the best response. There was no difference between the two groups in adverse events or side effects. Before and after treatment complete blood count, biochemical profile, and urinalysis revealed that there was no change from beginning to end and no difference between the groups. We conclude that terfenadine suspension is a safe, nonsedating antihistamine with an incidence of side effects no different from that of placebo. It is more effective than placebo in controlling symptoms of fall pollenosis in children.
Journal of Allergy and Clinical Immunology.
