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Biomedical subjects

J Scott Ferguson

Publications and source records attributed to J Scott Ferguson.

8 recordsLinked to original sources

Closure of a bronchopleural fistula using bronchoscopic placement of an endobronchial valve designed for the treatment of emphysema.

Pneumothoraces are sometimes complicated by a persistent air leak or bronchopleural fistula requiring prolonged chest tube drainage. Non-surgical treatment of persistent bronchopleural fistulas is often performed in patients who are poor surgical candidates, but the ideal method of closure is not known. Here we report closure of a persistent distal bronchopleural fistula using a one-way endobronchial valve designed for the treatment of emphysema.

Bronchial Fistula↗

Management of obstructing pulmonary broncholithiasis with three-dimensional imaging and holmium laser lithotripsy.

Major airway obstruction due to broncholithiasis produces significant morbidity, and management is difficult. Many of the patients are elderly and are not good candidates for surgical removal. Bronchoscopic removal may be limited due to anatomic considerations, skill of the bronchoscopist, and exposure of the patient to additional procedural risks. Preprocedural planning with three-dimensional (3D) multidetector CT (MDCT) imaging enhances the bronchoscopist's knowledge of the relationships of the target lesions with critical structures, and improves the efficiency of the application of specific endobronchial therapies. Here we report our experience treating obstructing broncholithiasis in two patients utilizing pretreatment planning with 3D MDCT imaging, followed by bronchoscopically delivered holmium laser fragmentation of the stones.

Aged↗

Use of 3-dimensional computed tomography reconstruction studies in the preoperative assessment of patients undergoing balloon dilatation for tracheobronchial stenosis.

BACKGROUND: Balloon dilatation (BD) is a useful method of treating tracheobronchial stenosis (TBS); however, accurate preoperative identification of the lesion is difficult. Three-dimensional computed tomography (3D-CT) is an imaging method that may allow more accurate definition of the lesion(s) preoperatively. STUDY OBJECTIVE: It is the aim of this study to present our finding using 3D-CT as a part of the preoperative evaluation of patients with TBS undergoing BD. METHODS: We studied a prospective case series of 17 consecutive patients who underwent 29 BDs for TBS from a variety of benign and malignant causes at a tertiary care hospital. All patients had a preoperative spiral CT; these data were processed by a software program, VIDA, which was developed at this institution, and 3D-CT reconstruction images of the TBS were created. This enabled accurate preoperative anatomic definition of the lesion. The patients subsequently underwent BD. RESULTS: All 17 patients had lesions identified with 3D-CT. Six patients had tracheal lesions and 12 patients had main stem lesions. One patient had combined tracheal and main stem lesions and 2 other patients had bilateral main stem lesions. Nine out of 17 patients required only one BD. One patient had a failed BD. The remaining 6 patients required more than one BD for optimal results (up to a maximum of 4). The follow-up period ranged from 1 to 34 months. CONCLUSIONS: 3D-CT offers accurate definition of TBS, including anatomic location, number of lesions present and status of airway distal to lesion. In this study, all preoperative lesions were correctly identified prior to BD.

Adult↗

Virtual bronchoscopy.

Virtual bronchoscopy is rapidly providing a software solution for visualization and measurement of the human airway tree with data derived from multirow detector X-ray CT scans as the most common data source. Increasingly, other imaging data sources to create three-dimensional image renderings of the bronchial tree are being used including magnetic resonance imaging, ultrasound, and the digital color image taken by the bronchoscope itself. Software solutions now exist for providing simple renderings of the bronchial tree through which a fly-through of the airway lumen by the center line of the airway can be added (the fly-through mimics the view that a real flexible bronchoscope affords the operator). The images so produced are visually accurate (i.e., they appear very realistic) and with good software now available are also analytically correct (i.e., measurements taken from these images are accurate). More advanced virtual bronchoscopic applications, including image-based pathfinding to mediastinal and peripheral lung structures, are also in development. Synergistic datasets composed of image data from multiple image sources are also being developed.

Bronchial Diseases↗

Pulmonary surfactant protein a inhibits macrophage reactive oxygen intermediate production in response to stimuli by reducing NADPH oxidase activity.

Alveolar macrophages are important host defense cells in the human lung that continuously phagocytose environmental and infectious particles that invade the alveolar space. Alveolar macrophages are prototypical alternatively activated macrophages, with up-regulated innate immune receptor expression, down-regulated costimulatory molecule expression, and limited production of reactive oxygen intermediates (ROI) in response to stimuli. Surfactant protein A (SP-A) is an abundant protein in pulmonary surfactant that has been shown to alter several macrophage (Mphi) immune functions. Data regarding SP-A effects on ROI production are contradictory, and lacking with regard to human Mphi. In this study, we examined the effects of SP-A on the oxidative response of human Mphi to particulate and soluble stimuli using fluorescent and biochemical assays, as well as electron paramagnetic resonance spectroscopy. SP-A significantly reduced Mphi superoxide production in response to the phorbol ester PMA and to serum-opsonized zymosan (OpZy), independent of any effect by SP-A on zymosan phagocytosis. SP-A was not found to scavenge superoxide. We measured Mphi oxygen consumption in response to stimuli using a new oxygen-sensitive electron paramagnetic resonance probe to determine the effects of SP-A on NADPH oxidase activity. SP-A significantly decreased Mphi oxygen consumption in response to PMA and OpZy. Additionally, SP-A reduced the association of NADPH oxidase component p47(phox) with OpZy phagosomes as determined by confocal microscopy, suggesting that SP-A inhibits NADPH oxidase activity by altering oxidase assembly on phagosomal membranes. These data support an anti-inflammatory role for SP-A in pulmonary homeostasis by inhibiting Mphi production of ROI through a reduction in NADPH oxidase activity.

Humans↗

Development and stability of insecticide resistance in the leafminer Liriomyza trifolii (Diptera: Agromyzidae) to cyromazine, abamectin, and spinosad.

Three populations of the leafminer, Liriomyza trifolii (Burgess), were collected from commercial ornamental production greenhouses in the United States and tested for susceptibility to three commercial insecticides. A leaf dip bioassay of leaves containing young (1-2-d-old) larvae was used. Based on larval mortality and compared with a susceptible laboratory reference colony, the three strains varied in spectrum and level of resistance to the insecticides. CA-1, collected from Gerbera daisy, was moderately resistant to cyromazine (18.1-fold) and abamectin (22.0-fold), but highly resistant to spinosad (> 188-fold). CA-2, collected from chrysanthemums, was not resistant to abamectin, had a low level of resistance to cyromazine (8.2-fold), but was extremely resistant to spinosad (1,192-fold). GA-1, collected from chrysanthemums, had very low levels of resistance to cyromazine (5.4-fold) and spinosad (1.9-fold) but was moderately resistant to abamectin (30.6-fold). When reared in the absence of insecticide selection pressure, all three strains reverted to approximately the level of the reference strain. The CA-1 strain reverted in nine generations to cyromazine; however, the lowest levels of abamectin and spinosad resistance reverted to was 3.1-fold at F8 and 3.2 at the F10, respectively. The CA-2 strain reverted in five generations to both cyromazine and spinosad. GA-1 reverted in five generations to abamectin. Based on the results, resistance to these three insecticides was unstable. Additionally, there was no cross-resistance among these three insecticides.

Animals↗

Complement protein C3 binding to Mycobacterium tuberculosis is initiated by the classical pathway in human bronchoalveolar lavage fluid.

In high concentrations of fresh nonimmune human serum, Mycobacterium tuberculosis activates the alternative pathway of complement and binds C3 protein, resulting in enhanced phagocytosis by complement receptors on human alveolar macrophages. Yet in the lung, the alternative pathway of complement is relatively inactive compared to the classical pathway. To begin to determine whether C3 opsonophagocytosis of M. tuberculosis by alveolar macrophages can occur in the lung of the immunologically naive host, we characterized the binding of C3 to M. tuberculosis in different concentrations of fresh nonimmune human serum and concentrated human bronchoalveolar lavage fluid. Here we show that in human serum, C3 binding to M. tuberculosis is rapid, initiated by either the alternative pathway or the classical pathway, depending on the concentration of serum, and occurs by covalent linkages between the bacterial surface and the C3 cleavage products, C3b or C3bi. Human bronchoalveolar lavage fluid contains C3 protein and functional classical pathway activity that mediates the binding of C3 to the surface of M. tuberculosis. These studies provide evidence that when M. tuberculosis is first inhaled into the lungs of the human host, the bacterium is opsonized by C3 cleavage via classical pathway activation within the alveolus, providing a C3-dependent entry pathway into resident alveolar macrophages.

Bronchoalveolar Lavage Fluid↗

Surfactant protein D inhibition of human macrophage uptake of Mycobacterium tuberculosis is independent of bacterial agglutination.

The innate immune system in the lung is essential for controlling infections due to inhaled pathogens. Mycobacterium tuberculosis (M.tb) encounters components of the innate immune system when inhaled into the lung, but the consequences of these interactions are poorly understood. Surfactant protein D (SP-D) binds to and agglutinates M.tb bacilli, and reduces the uptake of the bacteria by human macrophages. In the current studies, we utilized a recombinant SP-D variant (CDM) that lacks the collagen domain to further characterize the interaction of SP-D with M.tb, and determine the effects of agglutination on bacterial uptake by human monocyte-derived macrophages. These studies demonstrate that the binding of SP-D and CDM to M.tb is saturable and inhibited by carbohydrate competition and Ca(2+) chelation, implicating the carbohydrate recognition domain in the interaction. Fluorescence microscopy reveals that dodecameric SP-D leads to agglutination of the bacilli, whereas the trimeric CDM does not, demonstrating that the multivalent nature of SP-D is essential for agglutination of M.tb. However, preincubation of M.tb with increasing concentrations of SP-D or CDM leads to a concentration-dependent reduction in the uptake of the bacteria by macrophages, indicating that agglutination does not play a direct role in this observation. Finally, the reduced uptake of M.tb by SP-D is associated with reduced growth of M.tb in monocyte-derived macrophages. These studies provide direct evidence that the inhibition of phagocytosis of M.tb effected by SP-D occurs independently of the aggregation process.

Agglutination Tests↗