Elizabeth A. Perkett

AVISA

Rationale: In cystic fibrosis (CF), pulmonary exacerbations present an opportunity to define the effect of antibiotic therapy on systemic measures of inflammation. Objectives: Investigate whether plasma inflammatory proteins demonstrate and predict a clinical response to antibiotic therapy and determine which proteins are associated with measure...

Background and methods: Non-physician providers (NPPs) including nurse practitioners (NPs) and physician assistants (PAs) are important members of CF care teams, but limited data exist about the extent NPPs are involved in CF care. A subcommittee was established by the CF Foundation to gather information about current involvement of NPPs. Surveys...

Progressive pulmonary disease and infections with Pseudomonas aeruginosa remain an intractable problem in cystic fibrosis (CF). At the cellular level, CF is characterized by organellar hyperacidification, which results in altered protein and lipid glycosylation. Altered pH of the trans-Golgi network (TGN) may further disrupt the protein processing...

The CFTR gene encodes a chloride channel with pleiotropic effects on cell physiology and metabolism. Here, we show that increasing cGMP levels to inhibit epithelial Na(+) channel in cystic fibrosis (CF) respiratory epithelial cells corrects several aspects of the downstream pathology in CF. Cell culture models, using a range of CF cell lines and pr...

Cystic fibrosis (CF) remains a fatal progressive disease in spite of the discovery and characterization of the CFTR gene. Transforming growth factor beta (TGF-beta) has been implicated in pathophysiology of CF. Previous reports have shown the trans-Golgi network (TGN) is hyperacdified in CF epithelial cells in culture and that this hyperacidificati...

Endosomal hyperacidification in cystic fibrosis (CF) respiratory epithelial cells is secondary to a loss of sodium transport control owing to a defective form of the CF transmembrane conductance regulator CFTR. Here, we show that endosomal hyperacidification can be corrected by activating the signalling cascade controlling sodium channels through c...

Little empirical data exist about how adolescents with asthma, their parents, and pediatricians view the risks and benefits associated with asthma clinical research. Two studies examined similarities and differences in the perception of risks and benefits associated with asthma research. In study I questionnaires were completed by adolescents with...

A new link between the genetic defect and lung pathology in cystic fibrosis (CF) has been established by the recent discovery of an abnormally acidic pH in the organelles of CF respiratory epithelial cells, along with an increased acidity of the CF airway surface liquid. The defect in cystic fibrosis transmembrane resistance regulator (CFTR) result...

Anatomic remodeling and permanent closure of the newborn ductus arteriosus appears to require the development of intense hypoxia within the constricted vessel wall. Hypoxic ductus smooth muscle cells express vascular endothelial cell growth factor (VEGF). We studied premature baboons and sheep to determine the effects of VEGF inhibition (in baboons...

Recent studies have demonstrated high levels of vascular endothelial growth factor (VEGF) in exudative pleural effusions and a possible etiologic role. The factors regulating VEGF accumulation in the pleural space are unknown. Transforming growth factor (TGF)-beta is a potent stimulator of VEGF expression in vitro. We hypothesized that TGF-beta ind...

The purpose of this study was to analyze the relationship of the pleural fluid vascular endothelial growth factor (VEGF) level with the diagnostic category and with the pleural fluid characteristics in a group of 70 patients. The VEGF levels of consecutive patients undergoing therapeutic thoracentesis were determined with an enzyme-linked immunosor...

Exposure to high levels of inspired oxygen leads to respiratory failure and death in many animal models. Endothelial cell death is an early finding, before the onset of respiratory failure. Vascular endothelial growth factor (VEGF) is highly expressed in the lungs of adult animals. In the present study, adult Sprague-Dawley rats were exposed to >95...

Purpose: The purpose of this study was to analyze the levels of TGFβ1 and TGFβ2 in the pleural effusions of different etiologies and to determine if the levels were related to the diagnosis or the constituents of the pleural fluid. TGFβ is a fibrogenic cytokine. Methods: The pleural fluid levels of TGFβ1 and TGFβ2 levels in 33 patients (malignancy...

Chronic lung disease in neonates results from both lung injury and inadequate repair processes. Little is known about the growth factors involved in lung injury and repair, but vascular endothelial growth factor (VEGF) has recently been reported in several animal models of lung injury. VEGF is an endothelial cell-specific mitogen, which is also kno...

While it is well known that chronic pulmonary hypertension is accompanied by characteristic structural changes in the pulmonary arteries, it is becoming increasingly apparent that the remodeling process also involves the venous side of the circulation. The present paper utilizes a sheep model of sustained pulmonary hypertension induced by continuou...

In full-term newborns, permanent closure of the ductus arteriosus is associated with the formation of a neointima that is characterized by extracellular matrix deposition and smooth muscle cell migration. Transforming growth factor-beta (TGF-beta), a potent modulator of extracellular matrix deposition and smooth muscle cell migration, has been foun...

Continuous air embolization (CAE) into the pulmonary arterial circulation of sheep results in functional and structural changes of chronic pulmonary hypertension. Release of elastin peptides into lung lymph during CAE and attenuation of CAE-induced pulmonary hypertension by neutrophil depletion suggest that neutrophil elastase may contribute to the...

A number of growth factors have been identified that participate in lung growth and repair. The early stages of the repair cascade are important in preventing the later development of fibrosis. Both transforming growth factor-beta and basic fibroblast growth factor can have beneficial effects when given early in some injury models. Keratinocyte gro...

Transforming growth factor-beta (TGF-beta) has been suggested as one of the mediators of vascular remodeling in chronic pulmonary hypertension. We have previously shown a transient early increase in TGF-beta levels in lung lymph during the development of sustained pulmonary hypertension in a sheep model (12 days of air embolization). The present st...

The adult respiratory distress syndrome (ARDS) is sometimes associated with the onset of sustained pulmonary hypertension (Zapol and Snider 1977) and accompanying structural remodelling of the pulmonary arterial circulation — increased medial thickness of preacinar arteries, reduction in peripheral arterial bed and appearance of muscle in walls of...

Chronic pulmonary hypertension is associated with arterial structural remodeling. Insulin-like growth factor I (IGF-I) has been proposed as one of the mediators of vascular change because of its ability to stimulate proliferation in, and elastin production by, cultured vascular smooth muscle cells. We have shown previously that 12 days of continuou...

Evidence has accumulated suggesting that the various isoforms of beta-type transforming growth factors (TGF-beta s) regulate important functions in the lung; however, the cellular source of these proteins is not well defined. Northern blot analysis of murine lung tissue demonstrates that mRNA transcripts for all three TGF-beta isoforms are found fr...

The progression of structural changes in the pulmonary arterial bed were followed in a model of chronic pulmonary hypertension. Chronically instrumented awake sheep received continuous air embolization for 0 (controls), 1, 4, 8, or 12 days (n = 5-6/group). After the period of embolization, the lungs were removed, the pulmonary arteries were distend...

Evidence has accumulated suggesting that the various isoforms of β-type transforming growth factors (TGF-βs) regulate important functions in the lung; however, the cellular source of these proteins is not well defined. Northern blot analysis of murine lung tissue demonstrates that mRNA transcripts for all three TGF-β isoforms are found from birth t...

A serotonin-secreting human pancreatic carcinoid cell line (BON) is demonstrated to express transcripts for all three mammalian types of transforming growth factor beta (TGF beta 1, 2, and 3). Similarly, freshly excised carcinoid tumors from six patients were also found to express mRNA for all three of the type-beta TGFs. Medium conditioned by BON...

Chronic pulmonary hypertension is associated with extensive structural remodeling of the pulmonary arterial bed. The structural changes in the arterial walls include increased production of extracellular matrix components and smooth muscle cell hypertrophy, changes that have been similarly induced by transforming growth factor-beta (TGF-beta) in cu...

Chronic pulmonary hypertension can develop in diseases associated with acute or repeated inflammation in the lungs, e.g., adult respiratory distress syndrome, chronic bronchitis. Inflammation has also been associated with some animal models of chronic pulmonary hypertension. We have previously shown that 12 days of continuous air embolization into...

It has been suggested that the lung has only a narrow range of structural responses to injury. For example, long-term injury results in emphysema, fibrosis, and pulmonary hypertension. Clinical and experimental models of chronic pulmonary hypertension suggest that this disease can be triggered by a number of interventions and that the structural ch...

Baseline pulmonary arterial, left atrial and systemic artery pressures, cardiac output, and lung lymph flow were measured in seven chronically catheterized sheep before continuous air embolization into the pulmonary artery, which caused a two-to-threefold increase in pulmonary vascular resistance (PVR) for 12 days. Air embolization was discontinued...

Using a large animal model of radiation lung injury--the sheep exposed to bilateral thoracic irradiation--we have recently shown the development of sustained pulmonary hypertension during the first 4 weeks following radiation. This is the period prior to the onset of pneumonitis and pulmonary fibrosis. In the present study, we have examined biopsy...

Changes in vascular permeability are associated with structural damage to endothelial cells. These functional and structural changes can be produced experimentally and examined by using intimal explants from bovine pulmonary artery. Correlation of functional with structural changes allows us to dissect the mechanisms responsible for endothelial dam...

Six chronically catheterized sheep were exposed to 1,500-rad whole-lung irradiation and followed for a four-week period. Pulmonary arterial, left atrial and systemic arterial pressures, cardiac output, arterial blood gases, and pH were measured at base line and biweekly following radiation. Pulmonary vasoreactivity to 12% O2, 100% O2, and an analog...

An intravenous infusion of endotoxin into sheep results in accumulation of equal numbers of lymphocytes and granulocytes in the pulmonary microcirculation. The role of the sequestered lymphocytes in acute lung injury is not known. The present study examines whether lymphocyte migration through pulmonary endothelium contributes to endothelial damage...

Over a four-year period (1974-1978), twenty-two infants treated in the Vanderbilt Neonatal Intensive Care Unit developed bronchopulmonary dysplasia (BPD). These infants represented 2.5% of those requiring mechanical ventilation during this time (920). Thirteen of the twenty-two had the diagnosis of clinical hyaline membrane disease (HMD). All requi...

. Studies in animals have documented the presence of a laryngeal chemoreflex. This reflex reflex in apnea when water is placed in the laryngeal area. This study of ten premature infants presents data that would support the existence of a similar reflex response in some premature infants. All ten infants studied had apnea of unknown etiology.

A regionalization program, initiated in 1973 at Vanderbilt University Medical Center, has included community hospital site visits, formal nursing courses, and neonatal transport. The neonatal transport program was designed not only to give initial medical care to the sick newborn, but also to develop the educational aspects of the regionalization p...

Initial care of the sick neonate is crucial to his outcome. To improve this care, a full-time transport team of nurses, fellows, and faculty was established in 1974 that provided nurse-physician education, consultation, and neonatal transport. An 80 hour didactic course on the recognition and stabilization of the high risk neonate was attended by 2...