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Biomedical subjects

Manu Jain

Publications and source records attributed to Manu Jain.

9 recordsLinked to original sources
PubMed2006

Bosentan for the treatment of systemic sclerosis-associated pulmonary arterial hypertension, pulmonary fibrosis and digital ulcers.

Systemic sclerosis (SSc) is a devastating multisytemic autoimmune disease associated with widespread vascular damage. Pulmonary arterial hypertension (PAH) occurs in a significant proportion of patients and contributes to the morbidity and mortality that occurs in this disease. The recent development of specific therapies for the treatment of PAH mandates the early recognition, appropriate evaluation and judicious management of PAH in patients with SSc. Because endothelin (ET)-1 plays an important role in the development of PAH in SSc, and may also contribute to the vascular damage and fibrosis that occur in multiple organs in patients with the disease, inhibiting the production and activity of ET-1 is an appealing strategy for the treatment of SSc. This article reviews the pathophysiology of SSc and its vascular complications, and critically evaluates the current knowledge regarding the potential role of the ET-1 receptor blocker bosentan in the management of patients with SSc.

Animals↗
PubMed2005

Cystic fibrosis patients have poor sleep quality despite normal sleep latency and efficiency.

STUDY OBJECTIVES: Cystic fibrosis (CF) patients may be predisposed to poor sleep quality due to upper and lower airway abnormalities and impaired gas exchange. Previous sleep investigations of CF patients using single-night polysomnography have reported conflicting results. We hypothesized that sampling sleep for a prolonged period in a patient's normal environment may give a more representative assessment of sleep quality than a single-night polysomnogram, and that impaired sleep quality would correlate with pulmonary disease severity and self-assessed sleep quality. DESIGN: Using wrist actigraphy, we measured sleep quality in clinically stable CF patients and age-matched control subjects. In addition, each CF patient and control subject completed the following three questionnaires: the Epworth sleepiness scale; the Pittsburgh sleep quality index (PSQI); and the Medical Outcomes Study 36-item short form. RESULTS: Twenty CF patients and control subjects were enrolled in the study, and were well-matched for age, sex, and body mass index. The mean (+/- SD) FEV(1) for CF patients was 61.0 +/- 20.1% predicted. CF patients and control subjects had similar sleep duration, sleep latency, and sleep efficiency. However, CF patients had higher PSQI scores (6.45 vs 4.55, respectively; p = .04), a higher fragmentation index (FI) [31.72 vs 18.02, respectively; p < 0.001], and less immobile time (88.87 vs 91.89, respectively; p = 0.02). There was a significant correlation of FI with FEV(1) and PSQI scores. CONCLUSIONS: Stable CF patients have disrupted sleep, and sleep disruption may in part be related to the severity of pulmonary disease. In addition, the PSQI may be useful in detecting CF patients with poor sleep quality.

Adult↗
PubMed2005

Effects of hypoxia on the alveolar epithelium.

An important role of the alveolar epithelium is to contribute to the alveolocapillary barrier, secrete surfactant to lower the surface tension, and clear edema. These are energy-requiring processes for which normal oxygenation is required. There are many clinical conditions in which alveolar epithelial cells are exposed to low oxygen concentrations and although they can adapt to hypoxia, there are alterations in cellular function that can impact clinical outcomes. Hypoxic alveolar cells maintain cellular ATP content by increasing glycolytic capacity and via the hypoxia inducible factor-1 activation of a myriad of genes including the vascular endothelial growth factor. In addition, they decrease ATP utilization by down regulating the high energy consuming Na,K-ATPase activity and protein synthesis. The alveolar epithelium is in close apposition to vascular endothelium, which facilitates efficient gas exchange and provides a physical barrier between luminal and interstitial/vascular spaces. Alveolar edema clearance is an active process requiring activity of many proteins of which the amiloride-sensitive sodium channel (ENaC) and Na,K-ATPase are important contributors. Exposure to hypoxia impairs alveolar edema clearance by mechanisms that down regulate both ENaC and the Na,K-ATPase function. Other effects of hypoxia on alveolar cell function include surfactant production, disruption of cytoskeleton integrity, and the triggering of apoptosis. In summary, hypoxia has deleterious effects on the alveolar epithelium. More research needs to be done to better understand the effects of hypoxia on alveolar epithelia cell and lung function.

Animals↗
PubMed2004

Active transforming growth factor-beta1 activates the procollagen I promoter in patients with acute lung injury.

OBJECTIVE: Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes. DESIGN: Prospective controlled study of ALI/ARDS. SETTING: Intensive care units and laboratory of a university hospital. PATIENTS AND PARTICIPANTS: Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients. INTERVENTIONS: Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-beta1 levels were measured by ELISA. RESULTS: Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-beta1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-beta1 levels in the ARDS group compared to negative controls (-1.056 log(10)+/-0.1415 vs -1.505 log(10)+/-0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-beta1 levels were associated with more ventilator-free and ICU-free days. CONCLUSIONS: Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-beta1. Activated TGF-beta1 may impact ARDS outcome independent of its effect on procollagen I activation.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Type III secretion phenotypes of Pseudomonas aeruginosa strains change during infection of individuals with cystic fibrosis.

Pseudomonas aeruginosa is a frequent cause of respiratory exacerbations in individuals with cystic fibrosis. An important virulence determinant of this pathogen is its type III protein secretion system. In this study, the type III secretion properties of 435 P. aeruginosa respiratory isolates from 56 chronically infected individuals with cystic fibrosis were investigated. Although it had been previously reported that 75 to 90% of P. aeruginosa isolates from patients with hospital-acquired pneumonia secreted type III proteins, only 12% of isolates from cystic fibrosis patients did so, with nearly all of these isolates secreting ExoS and ExoT but not ExoU. Despite the low overall prevalence of type III protein-secreting isolates, at least one secreting isolate was cultured from one-third of cystic fibrosis patients. Interestingly, the fraction of cystic fibrosis patient isolates capable of secreting type III proteins decreased with duration of infection. Although 90% of isolates from the environment, the presumed reservoir for the majority of P. aeruginosa strains that infect patients with cystic fibrosis, secreted type III proteins, only 49% of isolates from newly infected children, 18% of isolates from chronically infected children, and 4% of isolates from chronically infected adults with cystic fibrosis secreted these proteins. Within individual patients, isolates of clonal origin differed in their secretion phenotypes, indicating that as strains persisted in cystic fibrosis patient airways, their type III protein secretion properties changed. Together, these findings indicate that following infection of cystic fibrosis patient airways, P. aeruginosa strains gradually change from a type III protein secretion-positive phenotype to a secretion-negative phenotype.

Adolescent↗
PubMed2003

Variability in interventions with pulmonary artery catheter data.

OBJECTIVES: To determine if intensivists given PAC data from critically ill patients make uniform management choices. DESIGN: Cross-sectional survey of board-certified intensivists. SETTING: Medical intensive care unit. PARTICIPANTS: Board-certified intensivists who are members of the American College of Chest Physicians and Society of Critical Care Medicine. INTERVENTIONS: A survey questionnaire containing three medical intensive care clinical vignettes was mailed to critical care physicians. Each vignette contained PAC data and one-half of the surveys contained echocardiographic (Echo) information. Every respondent was asked to select one of six interventions for each vignette. MEASUREMENTS: There were 126 evaluable surveys returned. In vignette 1 an intervention (none of the above) was selected by more than 50% of respondents. In vignettes 2 and 3, the most frequent selection was chosen only 44 and 37% of the times, respectively. There was a significant difference in the distribution of management choices between te Echo and the non-Echo subgroups. CONCLUSIONS: There is a significant heterogeneity in selecting an intervention based on PAC data among intensivists. The presence of Echo information may change the intervention selected but does not reduce heterogeneity. Any randomized trial evaluating efficacy of PAC's will have to have strict treatment protocols.

Attitude of Health Personnel↗
PubMed2001

Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa.

The type III secretion system of Pseudomonas aeruginosa transports four known effector proteins: ExoS, ExoT, ExoU and ExoY. However, the prevalence of the type III secretion system genes or the effector-encoding genes in clinical and environmental isolates of P. aeruginosa has not been well studied. Southern hybridization analyses and PCR were performed on over 100 P. aeruginosa isolates to determine the distribution of these genes. Clinical isolates were obtained from urine, endotracheal, blood and wound specimens, from the sputum of cystic fibrosis (CF) patients, and from non-hospital environmental sites. The popB gene was used as a marker for the presence of the large chromosomal locus encoding the type III secretion machinery proteins. Each isolate contained the popB gene, indicating that at least a portion of this large chromosomal locus was present in all isolates. Likewise, each isolate contained exoT-like sequences. In contrast, the exoS, exoU and exoY genes were variable traits. Overall, 72% of examined isolates contained the exoS gene, 28% contained the exoU gene, and 89% contained the exoY gene. Interestingly, an inverse correlation was noted between the presence of the exoS and exoU genes in that all isolates except two contained either exoS or exoU but not both. No significant difference in exoS, exoU or exoY prevalence was observed between clinical and environmental isolates or between isolates cultured from different disease sites except for CF respiratory isolates. CF isolates harboured the exoU gene less frequently and the exoS gene more frequently than did isolates from some of the other sites of infection, including the respiratory tract of patients without CF. These results suggest that the P. aeruginosa type III secretion system is present in nearly all clinical and environmental isolates but that individual isolates and populations of isolates from distinct disease sites differ in their effector genotypes. The ubiquity of type III secretion genes in clinical isolates is consistent with an important role for this system in human disease.

Bacterial Proteins↗