Abstract:
RATIONALE:High-dose isoniazid is recommended in short-course regimens for multidrug-resistant TB (MDR-TB). The optimal dose of isoniazid and its individual contribution to efficacy against TB strains with inhA or katG mutations are unknown. OBJECTIVE:Define the optimal dose of isoniazid for patients with isoniazid-resistant TB mediated by inhA mutations. METHODS:AIDS Clinical Trials Group A5312 is a Phase 2A, open-label trial in which individuals with smear-positive pulmonary TB with isoniazid resistance mediated by an inhA mutation were randomized to receive isoniazid 5, 10 or 15 mg/kg daily for 7 days (inhA group), and controls with drug-sensitive TB received standard dose (5 mg/kg/day). Overnight sputum cultures were collected daily. The 7-day early bactericidal activity of isoniazid was estimated as the average daily change in log10 colony forming units on solid media (EBACFU0-7) or as time to positivity in liquid media in hours (EBATTP0-7) using nonlinear mixed effects models. MEASUREMENTS AND MAIN RESULTS:Fifty-nine participants, 88% with cavitary disease, 20% HIV-positive, 16 with isoniazid-sensitive and 41 with isoniazid mono-resistant or MDR TB, were enrolled at one site in South Africa. Mean EBACFU0-7 at doses of 5, 10 and 15 mg/kg in the inhA group was 0.07, 0.17 and 0.22 log10CFU/mL/day, respectively, and 0.16 log10CFU/mL/day in controls. EBATTP0-7 patterns were similar. There were no drug-related Grade >3 adverse events. CONCLUSIONS:Isoniazid 10-15 mg/kg daily had similar activity against TB strains with inhA mutations as 5 mg/kg against drug-sensitive strains. The activity of high-dose isoniazid against strains with katG mutations will be explored next. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT01936831.
journal_name
Am J Respir Crit Care Medauthors
Dooley KE,Miyahara S,von Groote-Bidlingmaier F,Sun X,Hafner R,Rosenkranz SL,Ignatius EH,Nuermberger EL,Moran L,Donahue K,Swindells S,Vanker N,Diacon AH,A5312 Study Team.doi
10.1164/rccm.201910-1960OCsubject
Has Abstractpub_date
2020-01-16 00:00:00eissn
1073-449Xissn
1535-4970pub_type
杂志文章abstract::Monocyte deactivation has been identified as a major factor of immunosuppression in sepsis and is associated with a loss of surface human leukocyte antigen-DR (HLA-DR) expression on circulating monocytes. Using flow cytometry, quantitative reverse transcription-polymerase chain reaction, we investigated this phenomeno...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200309-1329OC
更新日期:2004-05-15 00:00:00
abstract:RATIONALE:Poor adherence is common in difficult-to-control asthma. Distinguishing patients with difficult-to-control asthma who respond to inhaled corticosteroids (ICS) from refractory asthma is an important clinical challenge. OBJECTIVES:Suppression of fractional exhaled nitric oxide (FeNO) with directly observed ICS...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201806-1182OC
更新日期:2019-02-15 00:00:00
abstract:RATIONALE:Lung cancer screening using computed tomography (CT) is effective in detecting lung cancer in early stages. Concerns regarding false-positive rates and unnecessary invasive procedures have been raised. OBJECTIVE:To study the efficiency of a lung cancer protocol using spiral CT and F-18-fluorodeoxyglucose pos...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200411-1479OC
更新日期:2005-06-15 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholiner...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1164/ajrccm.163.5.9903053
更新日期:2001-04-01 00:00:00
abstract:RATIONALE:Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions for respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment. OBJECTIVES:To characterize the blood genomic response in pat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201502-0355OC
更新日期:2015-10-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) is hypothesized to be influenced by genes within pathways involved with obesity, craniofacial development, inflammation, and ventilatory control. OBJECTIVES:We conducted the first candidate gene study of OSA using family data from European Americans and African Americans, select...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201002-0192OC
更新日期:2010-10-01 00:00:00
abstract:RATIONALE:Despite increasing recognition of bone morphogenetic protein (BMP) signaling in tissue remodeling, the expression pattern of ligands and signaling pathways remain undefined in the asthmatic airway. OBJECTIVES:To determine expression of BMP ligands (BMP-2, BMP-4, and BMP-7) and type I and type II receptors (A...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.200709-1376OC
更新日期:2008-05-15 00:00:00
abstract::The reaction of nitric oxide (NO) and superoxide anions (O(2)(-)) in the airway results in the formation of peroxynitrite, a highly reactive oxidant species. Peroxynitrite reacts with tyrosine residues in proteins to form the stable product nitrotyrosine. We investigated whether nitrotyrosine in exhaled breath condens...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.9912064
更新日期:2000-10-01 00:00:00
abstract:RATIONALE:Characteristics of and survival estimates for recipients of lung retransplantation in the modern era are unknown. OBJECTIVES:To compare lung retransplant patients in the modern era with historical retransplant patients, to compare retransplant patients with initial transplant patients in the modern era, and ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200707-1132OC
更新日期:2008-01-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) is associated with several pathophysiological deficits found in diabetic retinopathy (DR). Hence, it's plausible that OSA could play a role in the pathogenesis of sight-threatening DR (STDR). OBJECTIVES:To assess the relationship between OSA and DR in patients with type 2 diabet...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201701-0175OC
更新日期:2017-10-01 00:00:00
abstract::The relationship between the severity of obstructive sleep apnea (OSA) (measured by sleep study) and daytime sleepiness is poor. Variation in the degree of arousal accompanying obstructive respiratory events might help explain this poor correlation. Polysomnographic records from patients with OSA were reviewed in orde...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.1.9805074
更新日期:1999-01-01 00:00:00
abstract::Interpretation of incremental cardiopulmonary exercise tests (CPET) might be enhanced by considering the simultaneous rates of change of certain key variables, e.g., Delta oxygen uptake/Delta work rate (Delta VO(2)/Delta WR), Delta heart rate/Delta VO(2) (Delta HR/Delta VO(2)), Delta ventilation/Delta carbon dioxide p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.8.2103007
更新日期:2001-10-15 00:00:00
abstract::Rationale: Recent studies have demonstrated that extracellular vesicles (EVs) released during acute lung injury (ALI) were inflammatory.Objectives: The current study was undertaken to test the role of EVs induced and released from severe Escherichia coli pneumonia (E. coli EVs) in the pathogenesis of ALI and to determ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201812-2296OC
更新日期:2019-11-15 00:00:00
abstract::Controversy exists regarding the clinical utility of pleural fluid pH, lactate dehydrogenase (LDH), and glucose for identifying complicated parapneumonic effusions that require drainage. In this report, we performed a meta-analysis of pertinent studies, using receiver operating characteristic (ROC) techniques, to asse...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,meta分析
doi:10.1164/ajrccm.151.6.7767510
更新日期:1995-06-01 00:00:00
abstract:RATIONALE:Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high rates of HIV. OBJECTIVES:To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) and the fraction attributable to HIV, and to evaluate case detection. MET...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201008-1269OC
更新日期:2011-05-01 00:00:00
abstract::Relaxation was examined in diaphragm muscle strips of cardiomyopathic Syrian hamsters and control hamsters. Isotonic lengthening velocity and isometric tension decay were analyzed over the load continuum in response to twitch. For each load level (P), we measured the maximum extent of shortening (deltaL), the peak len...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.5.9154860
更新日期:1997-05-01 00:00:00
abstract:RATIONALE:Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. OBJECTIVES:We sought to identify donor, recipient, and perioperative risk factors for PGD. METHODS:We performed a 10-center p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201210-1865OC
更新日期:2013-03-01 00:00:00
abstract::Although skeletal muscle abnormalities have been described in association with human immunodeficiency virus (HIV), the effects of HIV infection on respiratory muscle function have not been well characterized. We hypothesized that HIV+ individuals may develop respiratory muscle weakness and that respiratory muscle dysf...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.3.9116990
更新日期:1997-03-01 00:00:00
abstract:RATIONALE:The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201503-0558OC
更新日期:2015-12-15 00:00:00
abstract::To compare the effectiveness of information delivered to family members of critically ill patients by junior and senior physicians, we performed a prospective randomized multicenter trial in 11 French intensive care units. Patients (n = 220) were allocated at random to having their family members receive information b...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.200305-645OC
更新日期:2004-02-15 00:00:00
abstract::Several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation, but their respective effects on the outcome of weaning from mechanical ventilation are not known. We conducted a randomized trial in three intensive care units in mechanically ventilated patients wh...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.150.4.7921460
更新日期:1994-10-01 00:00:00
abstract::Tracheal and lung parenchymal SP-LI (substance P-like immunoreactivity) and VIP-LI (vasoactive intestinal peptide-like immunoreactivity) content was measured in HPLC-purified tissue extracts from patients with and without asthma. We detected significantly less SP-LI in tracheal tissue from asthmatic than from nonasthm...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.2.7531100
更新日期:1995-02-01 00:00:00
abstract:RATIONALE:Breathing supplemental oxygen reduces breathlessness during exercise in patients with chronic obstructive pulmonary disease (COPD). Replacing nitrogen with helium reduces expiratory flow resistance and may improve lung emptying. Combining these treatments should be independently effective. OBJECTIVES:Study t...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.200506-925OC
更新日期:2006-04-15 00:00:00
abstract::Many patients who develop incapacitating illness have not expressed clear treatment preferences. Therefore, surrogate decision makers are asked to make judgments about what treatment pathway is most consistent with the patient's values. Surrogates often struggle with such decisions. The difficulty arises because answe...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201204-0710CP
更新日期:2012-09-15 00:00:00
abstract::Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries wit...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201907-1447OC
更新日期:2020-06-01 00:00:00
abstract::Protein tyrosine kinase signaling cascade plays a pivotal role in the activation of inflammatory cells. The purpose of this study was to investigate the effects of genistein, a broad-spectrum protein tyrosine kinase inhibitor, on airway inflammation in an in vivo guinea pig model of asthma. Guinea pigs were actively s...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200205-420OC
更新日期:2003-01-15 00:00:00
abstract::The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury that shares morphologic similarities to human bronchopulmonary dysplasia (BPD). Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of BPD. A neutrophil chemokine, cytokine-induced...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200402-215OC
更新日期:2004-12-01 00:00:00
abstract::Clinically, the spread of infectious agents between subjects undergoing spirometry is quite uncommon. There is almost no documentation in the medical literature on this subject. We studied the retrieval of nonpathogenic Escherichia coli after aerosolizing organisms into standard pulmonary function tubing of a type tha...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.2.9803116
更新日期:1999-02-01 00:00:00
abstract::This prospective and controlled pilot study evaluates the long-term effects of nocturnal oxygen therapy (NOT) on exercise endurance, hematology variables, quality of life, and survival of 23 adult patients (mean age, 32 +/- 6 yr) with post-tricuspid congenital heart defects (ventricular septal defect = 10; patent duct...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.164.9.2106076
更新日期:2001-11-01 00:00:00
abstract:RATIONALE:Data regarding the influence of ambient air pollution on infant bronchiolitis are few. OBJECTIVES:We evaluated the impact of several air pollutants and their sources on infant bronchiolitis. METHODS:Infants in the Georgia Air Basin of British Columbia with an inpatient or outpatient clinical encounter for b...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200901-0117OC
更新日期:2009-11-15 00:00:00