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J F Lewis

Publications and source records attributed to J F Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1996

Alveolar surfactant aggregate conversion in ventilated normal and injured rabbits.

Alveolar surfactant can be separated into two subtypes; large aggregates and small aggregates. Large aggregates represent the surface active form of surfactant and are the metabolic precursors of small aggregates. Previous studies examined the mechanism by which large aggregates are converted into small aggregates in vitro. We used intratracheal injection of radiolabeled large aggregates in rabbits to probe the aggregate conversion in vivo. After this injection, animals were mechanically ventilated for 60 min. After the animals were killed, the lungs were lavaged, and the percentage of radiolabel present in the small aggregate fraction was determined. Our results showed that ventilation resulted in aggregate conversion and that increases in tidal volume, but not in respiratory rate, correlated with increased conversion. Aggregate conversion in rabbits with acute lung injury correlated significantly with severity of injury. We conclude that a change in surface area (i.e., respiration) is necessary for aggregate conversion in vivo and that the ventilation strategy can affect this conversion. Furthermore, increased aggregate conversion in injured lungs might contribute to increased small-to-large aggregate ratios in these lungs compared with normal lungs.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury.

Two exogenous surfactant preparations [Survanta and bovine lipid extract surfactant (BLES)] were evaluated in saline lavage-injured adult sheep with two different delivery methods (instillation vs. aerosolization). Instilled BLES resulted in the greatest improvement in lung function, followed by aerosolized Survanta and then instilled Survanta. Aerosolized BLES was ineffective. Total surfactant recovery and distribution patterns were similar for Survanta and BLES for each delivery method tested. There were significant differences, however, in the proportion of surfactant recovered in the alveolar wash relative to the lung tissue between the groups at killing. Moreover, the ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates isolated from alveolar wash samples correlated with the physiological responses. The calculated contribution of secreted endogenous surfactant to the total alveolar phospholipid pool at killing was significantly greater for the aerosolized Survanta group compared with the aerosolized BLES group. This finding suggested that there were differences in the interaction of the exogenous surfactants and their alveolar environments. We conclude that the response to exogenous surfactant in acute lung injury depends not only on the preparation used but also on how the surfactants are delivered to the injured lung.

Animals↗
PubMed1996

Evaluation of surfactant treatment strategies after prolonged graft storage in lung transplantation.

We have previously documented alterations in endogenous surfactant after lung transplantation and improved graft function in some dogs after instillation of bovine lipid extract surfactant (bLES) into the recipient. To determine the effect of bLES delivery method and timing of treatment on physiologic response and surfactant recovery, 21 canine left lung grafts were divided into four groups: (1) Treatment of the donor for 3 h with aerosolized bLES prior to graft storage (Donor Aerosol); (2) Treatment of the recipient with instilled bLES immediately after transplantation (Recipient Instilled); (3) No bLES treatment (Control); and (4) Aerosolized bLES in donors and instilled bLES in recipients (Combined Therapy). Aerosolized bLES was labeled with [3H]-dipalmitoylphosphatidylcholine (DPPC) and instilled bLES with [14C]-DPPC. Grafts were stored for 36 h, transplanted and reperfused for 6 h. The native right and transplanted left lungs were then lavaged and protein yield, surfactant aggregates, and bLES recovery were measured. After 6 h of reperfusion, PO2/FlO2 ratio was significantly better after Combined Therapy (372 +/- 52 mm Hg) than in the Recipient Instilled (117 +/- 47 mm Hg) and Control groups (87 +/- 26 mm Hg), with intermediate values in Donor Aerosol dogs (232 +/- 64 mm Hg). The recovery of donor aerosolized bLES from transplanted lungs was increased in dogs given Combined Therapy versus Donor Aerosol treatment alone (p = 0.03). Furthermore, with Combined Therapy there was an increased percentage of instilled bLES recovered from transplanted lungs compared with the Recipient Instilled group. We conclude that surfactant treatment strategies influence physiologic response and bLES recovery after prolonged lung preservation. Treatment of lung donors with exogenous surfactant prior to graft storage was associated with less severe lung injury. Combined donor and recipient bLES therapy resulted in a superior physiologic response during reperfusion in this model.

Aerosols↗
PubMed1996

Surfactant associated protein-A inhibits human lymphocyte proliferation and IL-2 production.

The hyporesponsive state of lung-derived mononuclear leukocytes has been, in part, attributed to the effects of the lipid rather than the protein components of pulmonary surfactant. In the present study, however, the results suggest that purified preparations of pulmonary surfactant-associated protein A (SP-A) suppress both phytohemagglutinin (PHA, 1 microgram/ml)- and anti-CD-3 (1 to 10 ng/ml) activated proliferation of human peripheral blood and tonsillar mononuclear cells in a dose-dependent manner at concentrations as low as 50 pM (6.25 micrograms/ml) when added at the initiation of cultures. Addition of SP-A to PHA-stimulated peripheral blood mononuclear cells (PBMC) as late as 24 to 36 h after PHA was also capable of suppressing [3H]thymidine incorporation measured at 72 h. In contrast, concanavalin A (Con A; 2 micrograms/ml)-stimulated PBMC proliferation was slightly augmented by the addition of SP-A. Analysis of the supernatants of PHA-stimulated cultures treated with SP-A revealed that accompanying the inhibition of proliferation was a corresponding decline in measurable interleukin-2 (IL-2) concentrations, from 154 pg/ml for the PHA-treated cells to 57.8, 28.4, 5.2, and less than 2 pg/ml of IL-2 when SP-A was added at 6.25, 12.5, 25, and 50 micrograms/ml, respectively. We suggest that the action of SP-A on PHA-stimulated human PBMC may involve the blocking of a costimulatory signal crucial for in vitro T-cell activation.

Animals↗
PubMed1995

Transesophageal echocardiography in the evaluation of cardiac myxoma: a case of familial myxoma.

The vast majority of atrial myxomas are readily apparent on standard transthoracic echocardiography. We present the case of a young woman with known history of familial myxoma, in whom a large left atrial mass was identified on transthoracic echocardiography. Transesophageal study more clearly delineated the extent and origin of the tumor. In addition, an unsuspected tumor in the right ventricle was also identified. These findings were confirmed at surgery, and both masses were excised. The advantages of transesophageal echocardiography in evaluation and management of this unusual subset of patients with cardiac tumor are discussed.

Adult↗
PubMed1995

Factors influencing efficacy of exogenous surfactant in acute lung injury.

Exogenous surfactant is currently being tested as a therapeutic modality for patients with acute respiratory distress syndrome (ARDS). Animal studies have shown that several factors may influence the efficacy of this treatment modality. These factors include the surfactant delivery method used (instillation vs. aerosolization), the timing of surfactant treatment over the course of injury, the specific surfactant preparation used, and the dose of surfactant administered. Each of these factors alone and together may influence the interaction of the exogenous surfactant with the host's alveolar environment. This, in turn, may dictate how a specific patient responds to a particular surfactant treatment strategy. It is suggested that patients at an early stage of lung injury will benefit from aerosolized exogenous surfactant whereas large quantities of an instilled exogenous surfactant may be necessary at later stages of injury. Future studies will clarify how a specific surfactant treatment strategy should be chosen for an individual patient with ARDS.

Administration, Inhalation↗
PubMed1995

Pulmonary surfactant subfractions in patients with the acute respiratory distress syndrome.

Changes in the surfactant system have been observed in patients with acute respiratory distress syndrome (ARDS). These alterations in surfactant are thought to contribute to lung dysfunction in this disease. In this report we describe the changes in surfactant subfractions in bronchoalveolar wash obtained from five patients with established ARDS compared with five non-ARDS patients. Our results show that, in addition to the changes in surfactant composition and yield reported previously, the ratio of small to large surfactant aggregates is significantly increased in patients with ARDS compared with non-ARDS patients (0.48 +/- 0.09 versus 0.20 +/- 0.05 respectively [p < 0.05]). This increased ratio was associated with a decreased level of SP-A in the large aggregate fraction. We suggest that this increased ratio represents a marker for surfactant alterations in ARDS that is independent of lavage technique and can be measured in a very small surfactant sample.

Adult↗
PubMed1994

Clinical and morphologic expression of hypertrophic cardiomyopathy in patients > or = 65 years of age.

Hypertrophic cardiomyopathy (HC) is most often identified in patients in the second through fifth decades of life, but has been increasingly recognized in older patients. The present report characterizes morphologic and clinical features of HC in 134 consecutively studied patients aged > or = 65 years referred to a tertiary center. Echocardiographic or clinical evaluation, or both, was performed in 134 patients aged 65 to 85 years (mean 72) at most recent evaluation. Selected findings were compared with those in 64 youthful patients with HC aged 15 to 35 years (mean 25). Most elderly patients (120 of 134, 90%) developed marked symptoms that usually became evident after age 55 years; 94 of 120 experienced sustained improvement with medical treatment or operation. Elderly patients had relatively mild left ventricular (LV) wall thickening (20 +/- 3 mm), generally confined to the septum. In most (i.e., 68%), septal hypertrophy was uniformly distributed with parallel right and left borders and associated with elliptical LV cavity shape; however, in 32%, an inhomogeneously hypertrophied septum bulged into the left ventricle, disrupting normal cavity shape. Dynamic subaortic obstruction was present under basal or provocable conditions in a particularly small LV outflow tract in 103 of 134 patients (77%), and was usually produced by relatively restricted excursion of the anteriorly displaced mitral leaflets and posterior septal motion. HC is characterized by age-related differences in both clinical and morphologic expression. Elderly patients with HC characteristically demonstrate onset of cardiac symptoms late in life, as well as distinctive LV morphology and dynamics of outflow obstruction.

Adolescent↗
PubMed1994

Surface-area cycling of different surfactant preparations: SP-A and SP-B are essential for large-aggregate integrity.

Surface-area cycling is an in vitro procedure for the conversion of large into small surfactant aggregates. In this procedure a tube containing a surfactant suspension is rotated end-over-end at 37 degrees C so that the surface area of the suspension changes twice each cycle. We have utilized this method to study the mechanisms involved in aggregate conversion. Several different surfactant preparations were analysed: (1) bovine natural surfactant, a sucrose-gradient-purified material containing surfactant phospholipid and surfactant-associated proteins (SP-) SP-A, SP-B and SP-C; (2) bovine lipid-extract surfactant, which contains the surfactant phospholipids and SP-B and SP-C; (3) mixtures of dipalmitoyl phosphatidylcholine and phosphatidylglycerol (7:3, w/w) reconstituted with one or more surfactant proteins. Aggregate conversion was measured by phosphorus analysis of a 40,000 g supernatant (small aggregate) and pellet (large aggregates) before and after surface-area cycling. Surface-area cycling of lipid extract surfactant or lipids plus SP-B or SP-C resulted in rapid aggregate conversion. Lipids alone were not converted. Only a small percentage of purified natural surfactant was converted into small aggregates. Addition of SP-A to lipid extract surfactant could inhibit aggregate conversion of this material, but this was only observed when an additional 1% (w/w) of SP-B was added to the lipid extract. It is concluded that SP-A is important for large-aggregate integrity. It appears that SP-A acts in conjunction with SP-B. The presence of SP-B and/or SP-C is required for aggregate conversion; it is proposed that this reflects the necessity for lipid adsorption in aggregate conversion.

Animals↗
PubMed1994

Lung parenchyma and type II cell morphometrics: effect of surfactant treatment on preterm ventilated lamb lungs.

The effect of exogenous surfactant treatment on lung and type II cell structure of ventilated lambs of 137-138 days gestational age was studied. Thirty-four lambs were delivered and randomized to control or 100 mg/kg of natural sheep surfactant treatment groups. Lungs from one group of lambs not treated with surfactant were fixed before ventilation, and the other animals were ventilated to maintain normal blood gas values for 3, 24, or 48 h. Morphometric assessment of the inflation-fixed lung parenchyma of ventilated lungs was compared with the architectural appearance of alveoli and alveolar ducts in the unventilated lungs. Mechanical ventilation resulted in distension of alveolar ducts accompanied by the shallowing and loss of well-defined alveoli and areas of atelectasis at 3 h. These abnormalities increased in severity after 24 and 48 h of ventilation. Surfactant treatment before ventilation significantly reduced the extent and degree of dilatation and concomitant atelectasis. The fraction of normal parenchyma was 38 +/- 7% in untreated lambs vs. 64 +/- 6% in treated lambs after 24 h of ventilation. After 48 h of ventilation, significant differences between control (39 +/- 6%) and surfactant-treated (55 +/- 6%) lambs were still evident. Alveolar type II cells contained approximately 15% lamellar bodies by volume. Neither surfactant treatment nor time of ventilation altered the volume density of lamellar bodies or other organelles, except for a decrease in glycogen from 8% in nonventilated lungs to 2.5% in lungs ventilated for 24 h. These findings indicate that a surfactant treatment at birth results in the maintenance of more normal parenchyma with less atelectasis during prolonged ventilation of the immature lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Altered alveolar surfactant is an early marker of acute lung injury in septic adult sheep.

The purpose of this study was to characterize changes in the endogenous surfactant system in adult sheep rendered septic via cecal ligation and perforation (CLP). Forty-eight hours after CLP, septic animals had significant increases in mean pulmonary artery pressure (PAP) (p < 0.01), cardiac index (CI) (p < 0.01), and arterial lactate (p < 0.05) values compared with their respective baseline values, while the same measurements in a sham-operated control group did not change significantly. The changes in the septic group were associated with significantly lower PaO2 (p < 0.05) and alveolar to arterial (A-a) oxygen gradient values (p < 0.01) at 48 h compared with baseline measurements. No changes in oxygenation occurred within the sham-operated group. Surfactant phospholipid (PL) composition and surface activity measurements of isolated alveolar surfactant aggregate forms were similar for the two groups at 48 h. However, the ratio of poorly functioning small aggregate forms (SA) to superior functioning large aggregates (LA) was significantly increased in the septic versus the sham-operated animals (p < 0.01). This was associated with significantly decreased surfactant protein A (SP-A), B (SP-B), and C (SP-C) levels in septic versus sham-operated animals (p < 0.05). We conclude that sepsis-associated lung injury resulted in altered alveolar surfactant aggregate forms. These changes, together with altered surfactant protein levels, may represent a very sensitive marker of acute lung injury in high-risk patients. Furthermore, these findings suggest that exogenous surfactant given at an early stage of lung injury may mitigate progressive lung dysfunction.

Acute Disease↗
PubMed1994

Exogenous surfactant therapy in thirty-eight hour lung graft preservation for transplantation.

Previous work in our laboratory has documented alterations in surfactant composition and function after prolonged lung graft storage and transplantation in dogs (Am Rev Respir Dis 1993;148:208-15). To determine whether exogenous surfactant therapy was beneficial, we pretreated 13 canine double lung blocks with prostacyclin, flushed them with 4 degrees C modified Euro-Collins solution, and stored them at 4 degrees C for 37 to 38 hours. After left lung transplantation and immediately before reperfusion, eight dogs were administered 50 mg of bovine lung lipid extract surfactant per kilogram (50 mg/ml) directly into the left main bronchus and five served as nontreated control animals. Blood gases, peak inspired pressures, and individual pulmonary artery blood flows were measured every 30 minutes during 6 hours of reperfusion. The native right and transplanted left lungs were then lavaged and surfactant large and small aggregates and protein yields were analyzed. All nontreated animals had physiologic evidence of severe ischemia-reperfusion lung injury during reperfusion. Three of eight dogs treated with bovine lung lipid extract surfactant had near normal lung function at 6 hours of reperfusion, as reflected by maintenance of an oxygen tension/inspired oxygen fraction ratio of more than 400 mm Hg and a normal carbon dioxide tension. Five of eight dogs did not respond to surfactant therapy and had decreases in gas exchange identical to those of the control animals. Blood flow through the left pulmonary artery was maintained in the three animals that responded to exogenous surfactant, whereas flow significantly decreased to the left lung in all other animals, reflecting the patterns of gas exchange. In addition, the ratio of poorly functioning small surfactant aggregates to the well-functioning large aggregates isolated from lung lavage after 6 hours of reperfusion was decreased in surfactant-treated animals, especially in those exhibiting a beneficial physiologic response to surfactant therapy. We conclude that therapy with bovine lung lipid extract surfactant can result in excellent preservation of lung grafts after prolonged storage and transplantation, but that the results are not consistent. Further investigations are required to determine the factors responsible for the differential response to surfactant therapy.

Animals↗
PubMed1994

Corticosteroids and fetal intervention interact to alter lung maturation in preterm lambs.

The relationship between cortisol infusion and time of fetal catheterization on postnatal lung function of prematurely delivered lambs was investigated with the hypothesis that the intervention of catheterization would alter fetal responsiveness to the maturational effects of corticosteroids. Fetal catheterization was performed on d 117 or on d 122 of gestation. Cortisol or saline control infusions were begun on d 126, with delivery 60 h later on d 128. The animals were ventilated for 1.25 h after delivery, and compliance, the ventilation efficiency index, labeled albumin leak into and out of the lungs, alveolar and lung saturated phosphatidylcholine and surfactant protein A were measured to evaluate lung performance and biochemical indicators of maturation. Cortisol improved compliance and ventilation efficiency and decreased labeled albumin recovery without changing alveolar saturated phosphatidylcholine or surfactant protein A in the animals catheterized at 122 d relative to 122-d saline-infused animals. However, the animals catheterized at 117 d and infused with saline were as mature as assessed by compliance and ventilation efficiency as the 122-d cortisol-treated animals. The 117-d cortisol-infused animals had significantly augmented lung function relative to either 117-d saline-infused or 122-d cortisol-treated lambs and were the only group that had increased alveolar surfactant protein A and lung saturated phosphatidylcholine pool sizes. This study demonstrates that the response of the fetal lung to a maturational agent such as cortisol is dependent on the history of previous fetal interventions.

Albumins↗
PubMed1993

Degradation of surfactant-associated protein B (SP-B) during in vitro conversion of large to small surfactant aggregates.

Pulmonary surfactant obtained from lung lavages can be separated by differential centrifugation into two distinct subfractions known as large surfactant aggregates and small surfactant aggregates. The large-aggregate fraction is the precursor of the small-aggregate fraction. The ratio of the small non-surface-active to large surface-active surfactant aggregates increases after birth and in several types of lung injury. We have utilized an in vitro system, surface area cycling, to study the conversion of large into small aggregates. Small aggregates generated by surface area cycling were separated from large aggregates by centrifugation at 40,000 g for 15 min rather than by the normal sucrose gradient centrifugation. This new separation method was validated by morphological studies. Surface-tension-reducing activity of total surfactant extracts, as measured with a pulsating-bubble surfactometer, was impaired after surface area cycling. This impairment was related to the generation of small aggregates. Immunoblot analysis of large and small aggregates separated by sucrose gradient centrifugation revealed the presence of detectable amounts of surfactant-associated protein B (SP-B) in large aggregates but not in small aggregates. SP-A was detectable in both large and small aggregates. PAGE of cycled and non-cycled surfactant showed a reduction in SP-B after surface area cycling. We conclude that SP-B is degraded during the formation of small aggregates in vitro and that a change in surface area appears to be necessary for exposing SP-B to protease activity.

Animals↗
PubMed1993

Discordance in degree of right and left ventricular dilation in patients with dilated cardiomyopathy: recognition and clinical implications.

OBJECTIVES: The purpose of the present study was to assess the influence of variations in the relative degree of dilation of left and right ventricular chambers on the clinical outcome of patients with dilated cardiomyopathy. BACKGROUND: Dilated cardiomyopathy, a primary myocardial disease characterized by ventricular dilation and systolic dysfunction, is generally associated with a poor prognosis. However, considerable variability has been observed in the clinical course and the morphologic and hemodynamic features in individual patients. METHODS: We evaluated 67 consecutive patients with dilated cardiomyopathy and without evidence of ischemic or primary valvular heart disease. On the basis of diastolic ventricular chamber area measurements obtained by echocardiography, patients were classified into two groups: 38 patients with a relatively equal degree of left and right ventricular dilation (LV congruent to RV) and 29 patients with predominant and disproportionate dilation of the left ventricle (LV > RV). RESULTS: The 67 patients ranged in age from 19 to 81 years (mean 56); 49 (73%) were male. The two subsets of patients with dilated cardiomyopathy did not differ with regard to age, left ventricular diastolic dimension, wall thickness and mass or ejection fraction. However, patients in the LV congruent to RV group showed more severe mitral and tricuspid regurgitation by Doppler echocardiography than did those in the LV > RV group (p = 0.01 for mitral and 0.004 for tricuspid regurgitation). Over the follow-up period of 2 to 60 months (mean 28), there were 19 deaths. Survival in the LV > RV group was significantly better than in the LV congruent to RV group (p = 0.03). CONCLUSIONS: Patients with dilated cardiomyopathy represent a heterogeneous group with regard to both clinical outcome and the relative degree of left and right ventricular chamber dilation. Patients in the LV > RV subset appear to have better overall survival and less severe mitral and tricuspid regurgitation than do patients in the LV congruent to RV subset. Longitudinal studies are needed to determine whether these morphologic subsets in fact represent a continuum within the disease spectrum of dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1993

Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant.

Adult sheep (35 +/- 3 kg) underwent saline lung lavage and 1.5 h of mechanical ventilation to induce acute lung injury. Animals received 100 mg lipid/kg body wt of tracheally instilled surfactant (Inst Surf) or either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) and were killed 3 h later. Inst Surf and Neb Surf groups had significant improvements in oxygenation (P < 0.01) and peak inspiratory pressures (PIP) (P < 0.05) compared with pretreatment values. Improvements in oxygenation and PIP for Inst Surf animals were significantly greater than for Neb Surf animals (P < 0.05). Volumes of maximal pressure of quasi-static pressure-volume curves measured at the time the animals were killed were significantly greater for Inst Surf and Neb Surf animals than for animals given Neb Saline (P < 0.05). Alveolar recovery of exogenous surfactant was 100 times greater for Inst Surf animals (1,732 +/- 70 mg) than for Neb Surf animals (15.3 +/- 2.9 mg) at the time they were killed. Although there were no differences in exogenous surfactant distribution patterns at the lobar level between the two surfactant-treated groups, distribution histograms calculated for 10-g lung pieces revealed the Neb Surf animals had significantly more pieces within 25% of the mean value of 1.0 (42.7 +/- 6.9%) than did Inst Surf animals (20.8 +/- 5.5%) (P < 0.01). Exogenous surfactant therapy improved lung function with significantly different quantities of surfactant deposited in lung tissue for the two delivery methods evaluated.

Aerosols↗