Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adult respiratory distress syndrome (ARDS) is a complex syndrome in which pathogenesis is multifactorial. TNF-alpha, known to be pivotal in tissue damage, has been shown to have high levels in blood and alveolar fluid in ARDS. The identification of the cells responsible for this production in the alveolar milieu has not yet been reported. In order to evaluate the TNF-alpha gene expression in ARDS we have analyzed by in situ hybridization, using RNA probes, alveolar macrophages (AM) obtained by BAL from seven patients with ARDS, eight patients with miscellaneous respiratory diseases, and three control patients. In freshly collected AM from patients with ARDS, 66 +/- 14.5% cells expressed the TNF-alpha gene without in vitro stimulation. This TNF-alpha expression does not result from the BAL procedure itself since only a few unstimulated control AM contained TNF-alpha mRNA transcripts. TNF-alpha expression in AM is not restricted to patients with ARDS since it has also been observed in miscellaneous respiratory diseases; however, this expression is a constant feature in ARDS. These results demonstrated the major role of AM in the intra-alveolar production of TNF-alpha, and they point out the necessity in ARDS for a specific intra-alveolar therapy.
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PMID:Expression of tumor necrosis factor-alpha gene in alveolar macrophages from patients with the adult respiratory distress syndrome. 850 72

The aim of the study was to extend existing evidence that intratracheal aerosolization of LPS may serve as a very relevant model to study ARDS. The authors investigated the sequence of pathogenic events reflected by changes in levels of tumor necrosis factor alpha (TNF alpha), surfactant-associated protein A (SP-A) in BAL fluid, in addition to cell count, edema formation, and respiratory function. Within 24 h following intratracheal aerosolization of LPS in the rat, ARDS could be diagnosed according to the lung injury score for patients. This score includes the extent of the inflammatory density on chest X-rays, the severity of hypoxemia, the decline in lung compliance, and the level of PEEP (positive end expiratory pressure). In addition, other typical features of human ARDS appeared to be present in this model: (1) increased microvascular permeability reflected by edema, elevated levels of protein and of LDH, and increased numbers of PMNs in BAL fluid; (2) high levels of TNF alpha in BAL fluid preceding the appearance of PMNs; (3) changes in breathing pattern and a gradual development of respiratory failure with decreased compliance. SP-A levels in BAL fluid doubled within one hour after LPS administration, suggesting that this collectin may play a role in the immediate inflammatory response. Taken together, the findings presented here suggest that intratracheal LPS administration mimics the clinical development of ARDS very closely.
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PMID:Intratracheal aerosolization of endotoxin (LPS) in the rat: a comprehensive animal model to study adult (acute) respiratory distress syndrome. 920 56

The diagnosis of pulmonary candidiasis is still controversial. We undertook a prospective study on 25 non-neutropenic, mechanically ventilated (> 72 h) patients who died in our ICU with the aim of assessing the incidence and significance of the isolation of Candida species from quantitative cultures of immediate postmortem lung biopsies and different respiratory sampling techniques. Immediate postmortem respiratory samples (endotracheal aspirate, protected specimen brush [PSB], bronchoalveolar lavage [BAL], blind biopsies [average 14/patient], and bilateral bronchoscopically guided biopsies [two per patient]) were taken from all patients. Lung tissue specimens were histologically examined. Respiratory samples were classified as having Candida or otherwise. Ten (40%) patients had at least one pulmonary biopsy yielding Candida spp. Among these 10 patients with Candida isolates, only two had definite pulmonary candidiasis. A total of 470 microorganisms were isolated from 280 of 375 (77%) lung biopsy samples in all 25 patients. Candida species represented 9% (n = 40) of the isolates, corresponding to 10 patients (40%). In the 10 patients in whom Candida species was isolated from pulmonary biopsies, this was always associated with the isolation of the same microorganism from one of the sampling methods. Quantitative cultures of Candida species from different sampling methods correlated well among each other but could not discriminate the presence from absence of Candida pneumonia. A logistic regression model adjusted for the presence of antibiotics, days of antibiotic treatment, mechanical ventilation period, age, ARDS, parenteral nutrition, and gender did not show any independent risk factor for developing positive pulmonary samples for Candida species. The incidence of Candida isolation from pulmonary biopsies in critically ill mechanically ventilated, non-neutropenic patients who die is high (40%). However, the incidence of definite Candida pneumonia was 8%. We also found that Candida colonization is uniform throughout the different lung regions, and that the presence of Candida in respiratory samples, independently of quantitative cultures, is not a good marker of Candida pneumonia in critically ill, non-neutropenic, non-AIDS patients.
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PMID:Significance of the isolation of Candida species from respiratory samples in critically ill, non-neutropenic patients. An immediate postmortem histologic study. 927 44

Glucocorticoids, while potent antiinflammatory agents, have not been proven to be efficacious in Acute Respiratory Distress Syndrome, ARDS. Previous studies from this laboratory have reported that dexamethasone pretreatment of rats resulted in a 40-60% reduction in neutrophil influx into the airways following intratracheal administration of lipopolysaccharide, LPS. In the present study, the in vivo effects of dexamethasone on BAL neutrophil effector functions were evaluated by flow cytometry. BAL neutrophils from rats pretreated with dexamethasone (20 mg/kg, i.p. at 2 h before and 8 h after LPS) and harvested 20 h after LPS challenge demonstrated a 35% reduction in their ability to undergo an ex vivo oxidative burst with phorbol myristate acetate. This modest reduction in the oxidative burst was not related to a more general suppression of neutrophil effector functions as neither phagocytosis of opsonized bacteria nor expression of the beta-2 integrins CD11a and CD11b were similarly inhibited. Therefore, the neutrophil population which has migrated into the airways in dexamethasone pretreated rats retains the capacity to mediate host defense but also to exacerbate inflammation associated tissue damage.
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PMID:In vivo dexamethasone effects on neutrophil effector functions in a rat model of acute lung injury. 942 7

Activated neutrophils (PMN) have been implicated in the pathogenesis of adult respiratory distress syndrome (ARDS). Granulocyte colony-stimulating factor (G-CSF) is essential for PMN production and activation of PMN functions. We have recently shown that levels of G-CSF mRNA in a rat model of hemorrhagic shock correlated with severity of shock, PMN infiltration, pulmonary edema, and hypoxia. To determine whether increased tissue levels of G-CSF contribute to PMN recruitment and PMN-mediated injury, we instilled G-CSF into the lungs by intratracheal injection. Animals treated with G-CSF became hypoxic, hypocapnic, and alkalotic and demonstrated increased BAL fluid cellularity compared with control animals. The wet-to-dry ratio increased significantly after G-CSF instillation and peaked at 12 h. Histological examination of the lungs from G-CSF-treated rats revealed marked edema and increased PMN within the interstitium and alveoli. These results indicate that the presence of G-CSF alone in the lung can lead to recruitment of PMN, lung injury, and impaired pulmonary function, suggesting that local production of G-CSF may contribute to the development of lung damage and possibly ARDS in the setting of resuscitated hemorrhagic shock.
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PMID:G-CSF instillation into rat lungs mediates neutrophil recruitment, pulmonary edema, and hypoxia. 946 75

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage (DAD) secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or noninfectious insult. We have previously described a unique animal model in which CBA/J mice infected with reovirus 1/L develop ARDS. This model recapitulates the histopathological changes observed in human ARDS, which consist of the overlapping phases of exudation, including the formation of hyaline membranes, regeneration, and healing via repair with fibrosis. In this report, we show that the development of DAD in the acute phase of the disease and intraalveolar fibrosis in the late phase of the disease was not modulated by treatment with methylprednisolone (MPS). In the presence or absence of MPS, the majority of cells infiltrating the lungs after reovirus 1/L infection were polymorphonuclear leukocytes and macrophages. A number of key proinflammatory and anti-inflammatory cytokines/chemokines that are observed in the BAL fluid of ARDS patients were also found in the lungs of mice after reovirus 1/L infection and were not modulated by MPS. These include interferon-gamma, interleukin-10, and monocyte chemoattractant protein. The histopathology, cytokine/chemokine expression, and response to corticosteroids in reovirus 1/L-induced ARDS are similar to what is observed in human patients, making this a clinically relevant model.
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PMID:Respiratory reovirus 1/L induction of diffuse alveolar damage: pulmonary fibrosis is not modulated by corticosteroids in acute respiratory distress syndrome in mice. 1217 3

There is strong evidence that alterations in the pulmonary surfactant system play an important role in the pathophysiology of lung disease, including ARDS . Although it is still unclear whether mortality and morbidity of ARDS will be reduced, surfactant replacement therapy has been shown to improve oxygenation, improve lung compliance, and decrease the need for ventilatory support. The critical need for more standardized studies with one type of intratracheal surfactant and uniform measurements of surfactant proteins and phospholipids by BAL is evident. Further studies will also be needed to elucidate the optimal timing and dosage regimen for different disease processes. Some evidence supports the measurements of surfactant protein levels as markers for predicting the onset and outcome of ARDS and perhaps providing a window for early treatment of patients at risk to develop ARDS. Continued investigation into the role of surfactant in the immune regulation of the lung may also provide additional information to support the efficacy of surfactant replacement in lung disease.
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PMID:Surfactant biology and clinical application. 1284 15

The purpose of the present study was to investigate: (1) the acute effects of sulfur mustard on airway, lung, and surface tension of bronchoalveolar lavage fluid (BALfluid) in guinea pigs following intratracheal (i.t.) exposure to 1LD50 of an aerosolized solution of sulfur mustard in saline, and (2) the therapeutic efficacy of i.t. administration of the natural surfactant Curosurf and the broncholytic Salbutamol. Intratracheally aerosolized sulfur mustard solution induced two clinically relevant symptoms, that is, asthmalike symptoms reflected by an early bronchoconstriction and "late asthmatic responses" (LAR), and ARDS-like symptoms, that is, pulmonary edema and damage to the lung surfactant. The respiratory minute volume (RMV) was enhanced. Histologically, inflammation and severe epithelial injury in the upper airways were observed, whereas the lungs were homogeneously affected. The surface tension of BAL fluid derived at 24 h after sulfur mustard exposure was much higher (20 +/- 1 mN/m) than that of unexposed control animals (about 1.0 +/- 0.5 mN/m), indicating that the lung surfactant had been altered, and justifying treatment with exogenous surfactant. Intratracheal nebulization of a Salbutamol solution (10 microg/kg), or i.t. bolus administration of Curosurf (62.5 or 125 mg/kg), tended to reduce mortality, although Salbutamol appeared to be more effective than Curosurf in this respect. Although the present study does not give a definite answer to the question of whether the animal model used would be the most relevant for humans, a number of considerations in favor of i.t. aerosolization of sulfur mustard are discussed. Since it was noticed that sulfur mustard exposure induced damage to the lung surfactant, severe bronchoconstriction, and inflammation of the respiratory tract, the effectiveness of a combined treatment consisting of exogenous surfactant, anti-inflammatory drugs, and broncholytics is recommended to be further investigated.
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PMID:Asthmalike symptoms following intratracheal exposure of Guinea pigs to sulfur mustard aerosol: therapeutic efficacy of exogenous lung surfactant curosurf and salbutamol. 1520 45

Pneumonia is common in those patients placed in intensive care units, especially in mechanically ventilated patients. The high mortality rate of ventilator-associated pneumonia requires a rapid initiation of the appropriate antibiotic treatment. Patients who do not respond to initial antibiotic regimens could have the additional benefit of the use of invasive techniques such as bronchoalveolar lavage. Moreover, BAL is of clinical use to identify several non-infectious pulmonary conditions that may mimic pneumonia in these patients. Such conditions include pulmonary haemorrhages, acute eosinophilic pneumonia, malignancy, drug-induced toxicity, adult respiratory distress syndrome and cardiogenic pulmonary oedema. It is important to distinguish these conditions from pneumonia because the management and prognosis of these entities is quite different.
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PMID:Bronchoalveolar lavage in intensive care units. 1536 35

Polyethylene glycol (PEG)-electrolyte solution (Golytely), is most commonly used for bowel preparation before colonoscopy, as well as for barium enema and colon surgery. In this case, a 70-year-old man developed ARDS following the administration of Golytely by mouth before a scheduled colonoscopy. Aspiration of PEG-electrolyte solution was suspected, and the patient was successfully treated by BAL. Therefore, early bronchoscopy and BAL should be considered as initial treatment for PEG aspiration, because removal of PEG is most important for managing the disease.
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PMID:Aspiration pneumonia due to polyethylene glycol-electrolyte solution (Golytely) treated by bronchoalveolar lavage. 1819 28


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