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Biomedical subjects

J F Lewis

Publications and source records attributed to J F Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical relevance of chest pain during dobutamine stress echocardiography in women.

BACKGROUND: Dobutamine stress echocardiography (DSE) is commonly used for diagnosis and management of patients with known or suspected coronary artery disease. Chest pain occurring during DSE potentially provides additional diagnostic accuracy. Our experience suggests that chest pain occurs frequently in women undergoing DSE. HYPOTHESIS: It was the purpose of this study to determine the frequency with which chest pain occurs in women undergoing DSE and the relation to inducible ischemia or coronary artery stenosis. METHODS: To determine the prevalence and clinical significance or chest pain during DSE, we reviewed the records of 154 consecutive women undergoing DSE in our laboratory. Of these, 59 patients (37.5%) also underwent coronary angiography. The presence or absence of chest pain was correlated with ECG changes, left ventricular wall motion abnormalities during DSE, and coronary stenosis by angiography. RESULTS: Forty-one women (26%) developed chest pain during DSE. Patients experiencing chest pain were older (58.5 +/- 9.3 vs. 54.9 +/- 12.6; p = 0.05), and had lower resting heart rates (71 +/- 12.2 vs. 77.9 +/- 14.9; p = 0.008), but received similar maximum doses of dobutamine and reached comparable peak heart rates (131.1 +/- 17.4 vs. 133.5 +/- 21.7; p = NS). Patients with chest pain more commonly exhibited ST-segment depression > or = 1 mm during dobutamine infusion (13/41, 32%, vs. 17/113, 15%; p = 0.02), but chest pain showed no statistically significant correlation with abnormal DSE or with coronary stenosis. CONCLUSIONS: In women undergoing DSE, chest pain occurs in 26% and does not appear to be related to inducible myocardial ischemia. Electrocardiographic changes occur more frequently in patients who experience chest pain, but are also often unrelated to inducible myocardial ischemia.

Adolescent↗
PubMed1999

Dobutamine stress echocardiography in women with chest pain. Pilot phase data from the National Heart, Lung and Blood Institute Women's Ischemia Syndrome Evaluation (WISE).

OBJECTIVES: The aim of this project was to assess the utility of dobutamine stress echocardiography (DSE) for evaluation of women with suspected ischemic heart disease. BACKGROUND: Most investigations addressing efficacy of diagnosis and treatment of coronary artery disease (CAD) have been performed in predominantly male populations. As part of the Women's Ischemia Syndrome Evaluation (WISE) study, DSE was assessed in women participating at the University of Florida clinical site. METHODS: Women with chest pain or other symptoms suggestive of myocardial ischemia and clinically indicated coronary angiography were eligible for the WISE study. Enrolled subjects underwent DSE using a modified protocol. Coronary stenosis was assessed by core laboratory quantitative coronary angiography (QCA). RESULTS: The 92 women studied ranged in age from 34 to 82 years (mean 57.5). All women had > or = 1 major risk for CAD, and most (89, 97%) had > or = 2 risk factors. In 78 women (85%), left ventricular wall motion was normal at baseline and during peak infusion. The remaining 14 women had wall motion abnormalities during DSE. By QCA, 25 women (27%) had > or = 50% coronary stenosis, including 10 with single-vessel obstruction. Dobutamine stress echocardiography was abnormal in 10 of these 25 women, yielding overall sensitivity of 40%, and 60% for multivessel stenosis. Exclusion of women with inadequate heart rate response yielded overall sensitivity of 50%, and 81.8% for multivessel stenosis. Dobutamine stress echocardiography was normal in 54 of the 67 women with < 50% coronary narrowing, specificity 80.6%. CONCLUSIONS: Dobutamine stress echocardiography reliably detects multivessel stenosis in women with suspected CAD. However, DSE is usually negative in women with single-vessel stenosis, and in the larger subset without coronary stenosis. Ongoing protocols of the WISE study are expected to improve diagnostic accuracy in women with single-vessel disease, as well as provide important data in the substantial number of women with chest pain but without epicardial coronary artery stenosis.

Adult↗
PubMed1999

An examination of the different variables affecting surfactant aggregate conversion in vitro.

Pulmonary surfactant exists in 2 major subtypes, the freshly secreted, surface-active large surfactant aggregates (LA) and their metabolic product, the less surface active, small aggregates (SA). Conversion of LA into SA can be studied using an in vitro technique, surface area cycling, which involves the rotation of a suspension of LA end-over-end so that the surface area of the liquid changes twice each cycle. In order to further elucidate the mechanisms involved in aggregate conversion, we have examined the effects of time, temperature, change in surface area, cycling speed, surfactant concentration, and albumin on aggregate conversion in vitro. Three different surfactant preparations were used; rabbit LA, sheep LA, and an exogenous surfactant preparation, bovine lipid extract surfactant (BLES). Based on our results that showed that these variables affected aggregate conversion, we concluded that the adsorption of surfactant at the changing air-liquid interface was an important step in aggregate conversion. However, the results also indicated that aggregate conversion was not solely due to the adsorption characteristics of the surfactant. Other surfactant properties, such as the activity of serine protease or film stability at the air-liquid interface, may also be important in aggregate conversion.

Animals↗
PubMed1998

Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production.

Components of the airspace-lining material may contribute to the local regulation of immune function within the lung. We report here that recombinant rat pulmonary surfactant-associated protein D (SP-D) inhibits the lectin- and anti-CD3-stimulated proliferation of human PBMCs. Inhibition was associated with a decreased production of IL-2, and the addition of human rIL-2 blocked the inhibitory action of SP-D. These effects were not inhibited by maltose, indicating that the inhibitory activity was not dependent upon the lectin activity of SP-D. Studies employing mutant SP-D lacking N-linked sugars or defective in multimerization further indicated that inhibition was not dependent upon cellular interactions with the N-linked oligosaccharide on SP-D or the oligomerization of trimeric SP-D subunits. Although a peptide containing an inverted DGR showed similar IL-2-dependent effects on anti-CD3-stimulated proliferation, deletion of the conserved DGRDGR sequence near the amino-terminal end of the collagen domain did not decrease the suppressive activity of SP-D. We hypothesize that SP-D can dampen lymphocyte responses to exogenous stimuli and protect the lung against collateral immune-mediated damage.

Amino Acid Sequence↗
PubMed1998

Effects of dichloroacetate in patients with congestive heart failure.

BACKGROUND: Conventional approaches to management of congestive heart failure (CHF) rely on drugs that increase myocardial contractility or reduce ventricular afterload. These approaches often improve cardiac symptoms and survival, but may be associated with significant deleterious effects. An alternative approach is to enhance myocardial energy production. Dichloroacetate (DCA) stimulates pyruvate dehydrogenase activity and accelerates aerobic glucose, pyruvate, and lactate metabolism in myocardial cells. These alterations would be expected to improve myocardial function. HYPOTHESIS: The purpose of the investigation was to assess the efficacy of DCA in patients with left ventricular systolic dysfunction and to examine the mechanism by which improvement occurs. METHODS: A total of 25 patients (16 men, 9 women; age range 31-72 years, mean 59) with CHF and ejection fraction < or = 40% received an intravenous infusion of 50 mg/kg DCA over 15 min. Indices of systolic and diastolic function were obtained by two-dimensional and Doppler echocardiography performed at baseline, 30 min, and 60 min following completion of DCA infusion. RESULTS: Baseline ventricular ejection fraction was 27.3 +/- 9.1%; 17 patients (68%) had nonischemic cardiomyopathy. Heart rate increased after DCA infusion from 73.9 +/- 14.5 to 79.2 +/- 14.9 beats/min at 60 min; p = 0.02. Left ventricular diastolic and systolic volumes increased at 30 min compared with baseline (248.7 +/- 98.1 vs. 259.6 +/- 99.6; p = 0.04, and 180.1 +/- 80.4 vs. 192.2 +/- 84.9; p = 0.002, respectively), but stroke volume (49.2 +/- 19.1 vs. 48.9 +/- 18.1; p = 0.9) and ejection fraction (27.3 +/- 9.1 vs. 25.7 +/- 9.8; p = 0.2) were unchanged. Indices of diastolic function were also unchanged. CONCLUSION: Dichloroacetate infusion in patients with CHF is not associated with improvement in noninvasively assessed left ventricular function.

Adult↗
PubMed1998

Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor.

Investigation of possible mechanisms to describe the hyporesponsiveness of pulmonary leukocytes has led to the study of pulmonary surfactant and its constituents as immune suppressive agents. Pulmonary surfactant is a phospholipid-protein mixture that reduces surface tension in the lung and prevents collapse of the alveoli. The most abundant protein in this mixture is a hydrophilic molecule termed surfactant-associated protein A (SP-A). Previously, we showed that bovine (b) SP-A can inhibit human T lymphocyte proliferation and interleukin-2 production in vitro. Results presented in this investigation showed that different sources of human SP-A and bSP-A as well as recombinant rat SP-A inhibited human T lymphocyte proliferation in a dose-dependent manner. A structurally similar collagenous protein, C1q, did not block the in vitro inhibitory action of SP-A. The addition of large concentrations of mannan to SP-A-treated cultures also did not disrupt inhibition, suggesting that the effect is not mediated by the carbohydrate recognition domain of SP-A. Use of recombinant mutant SP-As revealed that a 36-amino acid Arg-Gly-Asp (RGD) motif-containing span of the collagen-like domain was responsible for the inhibition of T cell proliferation. A polyclonal antiserum directed against an SP-A receptor (SP-R210) completely blocked the inhibition of T cell proliferation by SP-A. These results emphasize a potential role for SP-A in dampening lymphocyte responses to exogenous stimuli. The data also provide further support for the concept that SP-A maintains a balance between the clearance of inhaled pathogens and protection against collateral immune-mediated damage.

Animals↗
PubMed1998

Effects of surfactant distribution and ventilation strategies on efficacy of exogenous surfactant.

The effects of both surfactant distribution patterns and ventilation strategies utilized after surfactant administration were assessed in lung-injured adult rabbits. Animals received 50 mg/kg surfactant via intratracheal instillation in volumes of either 4 or 2 ml/kg. A subset of animals from each treatment group was euthanized for evaluation of the exogenous surfactant distribution. The remaining animals were randomized into one of three ventilatory groups: group 1 [tidal volume (VT) of 10 ml/kg with 5 cmH2O positive end-expiratory pressure (PEEP)]; group 2 (VT of 5 ml/kg with 5 cmH2O PEEP); or group 3 (VT of 5 ml/kg with 9 cmH2O PEEP). Animals were ventilated and monitored for 3 h. Distribution of the surfactant was more uniform when it was delivered in the 4 ml/kg volume. When the distribution of surfactant was less uniform, arterial PO2 values were greater in groups 2 and 3 compared with group 1. Oxygenation differences among the different ventilation strategies were less marked in animals with the more uniform distribution pattern of surfactant (4 ml/kg). In both surfactant treatment groups, a high mortality was observed with the ventilation strategy used for group 3. We conclude that the distribution of exogenous surfactant affects the response to different ventilatory strategies in this model of acute lung injury.

Animals↗
PubMed1998

Effects of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury.

We evaluated the effects of various ventilation strategies on the efficacy of exogenous surfactant therapy in lung-injured adult rabbits. Lung injury was induced by repetitive whole-lung saline lavage followed by mechanical ventilation. Three hours after the final lavage, 100 mg lipid/kg bovine lipid extract surfactant was instilled. After confirmation of similar responses to exogenous surfactant, animals were then randomized to one of four ventilation groups; (1) Normal tidal volume (VT) (5 cm H2O): VT = 10 ml/kg, respiratory rate (RR) = 30/min, positive end-expiratory pressure (PEEP) = 5 cm H2O; (2) Normal VT (9 cm H2O): VT = 10 ml/kg, RR = 30/min, PEEP = 9 cm H2O; (3) Low VT (5 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 5 cm H2O; (4) Low VT (9 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 9 cm H2O. Animals were ventilated for an additional 3 h and then killed, and lung lavage fluid was analyzed. Animals ventilated with the low-VT modes (Low VT [5 cm H2O] and Low VT [9 cm H2O]) had higher PaO2 values (430 +/- 7 mm Hg and 425 +/- 18 mm Hg versus 328 +/- 13 mm Hg) and higher percentages of surfactant in large aggregate forms (83 +/- 2% and 82 +/- 2% versus 67 +/- 4%) at 3 h after treatment than did the Normal VT (5 cm H2O) group (p < 0.05). Increasing the PEEP level was beneficial for a short period after surfactant administration to maintain oxygenation, but did not affect exogenous surfactant aggregate conversion. We speculate that ventilation strategies resulting in low exogenous surfactant aggregate conversion will result in superior physiologic responses to exogenous surfactant.

Animals↗
PubMed1998

Characterizing alterations in the pulmonary surfactant system in a rat model of Pseudomonas aeruginosa pneumonia.

Bacterial pneumonia remains a significant cause of patient morbidity and mortality worldwide. Pulmonary surfactant serves to maintain homeostasis in the lung through the maintenance of alveolar stability and the regulation of the alveolar immune response. The purpose of this study was to characterize the lung injury and associated surfactant alterations in a rat model of acute Pseudomonas aeruginosa pneumonia. Pneumonia was induced in male Sprague-Dawley rats via intratracheal injection of 0.2 ml, phosphate-buffered saline (PBS) containing P. aeruginosa (6x10(8) colony-forming units x mL(-1)). Control animals received 0.2 mL sterile PBS. Twenty-four hours after inoculation, the pneumonia group (PN) exhibited clinical signs of pneumonia including deficits in gas exchange, leukopenia and elevated arterial lactate levels. Morphological assessment confirmed the presence of pneumonia with airspaces filled with polymorphonuclear cells. Lung homogenate analysis demonstrated evidence of bacterial colonization of pneumonic lung tissue. Lung compliance was also significantly lower in the PN group. Lung lavage analysis of PN rats revealed the pooled surfactant levels to be lower and the surfactant function reduced compared to control rats. Surfactant composition was also found to be altered in PN rats. These results demonstrate that in Pseudomonas aeruginosa pneumonia, the pulmonary surfactant system is both poorly functioning and reduced in quantity. These alterations may contribute to the lung dysfunction characteristic of this disorder.

Acute Disease↗
PubMed1997

Mitigation of injury in canine lung grafts by exogenous surfactant therapy.

BACKGROUND: Exogenous surfactant therapy of lung donors improves the preservation of normal canine grafts. The current study was designed to determine whether exogenous surfactant can mitigate the damage in lung grafts induced by mechanical ventilation before procurement. METHODS AND RESULTS: Five donor dogs were subjected to 8 hours of mechanical ventilation (tidal volume 45 ml/kg). This produced a significant decrease in oxygen tension (p = 0.007) and significant increases in bronchoscopic lavage fluid neutrophil count (p = 0.05), protein concentration (p = 0.002), and the ratio of poorly functioning small surfactant aggregates to superiorly functioning large aggregates (p = 0.02). Five other animals given instilled bovine lipid extract surfactant and undergoing mechanical ventilation in the same manner demonstrated no significant change in oxygen tension values, lavage fluid protein concentration, or the ratio of small to large aggregates. All 10 lung grafts were then stored for 17 hours at 4 degrees C. Left lungs were transplanted and reperfused for 6 hours. After 6 hours of reperfusion the ratio of oxygen tension to inspired oxygen fraction was 307 +/- 63 mm Hg in lung grafts administered surfactant versus 73 +/- 14 mm Hg in untreated grafts (p = 0.007). Furthermore, peak inspired pressure was significantly (p < 0.05) lower in treated animals from 90 to 360 minutes of reperfusion. Analysis of lavage fluid of transplanted grafts after reperfusion revealed small to large aggregate ratios of 0.17 +/- 0.04 and 0.77 +/- 0.17 in treated versus untreated grafts, respectively (p = 0.009). CONCLUSIONS: Instillation of surfactant before mechanical ventilation reduced protein leak, maintained a low surfactant small to large aggregate ratio, and prevented a decrease of oxygen tension in donor animals. After transplantation, surfactant-treated grafts had superior oxygen tension values and a higher proportion of superiorly functioning surfactant aggregate forms in the air space than untreated grafts. Exogenous surfactant therapy can protect lung grafts from ventilation-induced injury and may offer a promising means to expand the donor pool.

Animals↗
PubMed1997

Considerations for racial differences in the athlete's heart and related cardiovascular disease.

Athletic training is often associated with modest increases in left ventricular chamber size, wall thickness, and mass, which appear to be related to the level and intensity of training as well as the type of activity performed. It appears that for given levels and types of training, some individuals show more marked morphologic changes. It has been speculated that the cardiac alterations that occur with athletic conditioning may be due, in part, to genetic factors that exist independent of training. Related to this issue is the possibility that racial (or biologic) differences in cardiac response to exercise may also exist. This article reviews the available data that address racial differences in the cardiac response to exercise and to left ventricular pressure overload and the implications of these findings.

Adaptation, Physiological↗
PubMed1997

Effects of lung injury on pulmonary surfactant aggregate conversion in vivo and in vitro.

Within the alveolar space pulmonary surfactant is converted from the surface active large aggregates (LA) to the inactive small aggregates (SA). This conversion is affected by a change in surface area, lung injury, breathing pattern, and protease activity. This study examined the effect of N-nitroso-N-methylurethane-induced acute lung injury on aggregate conversion in mechanically ventilated and spontaneously breathing rabbits. Both the in vitro surface area cycling techniques and the in vivo technique of intratracheally injecting radiolabeled LA were used for analyzing aggregate conversion. Mechanical ventilation of injured lungs resulted in increased aggregate conversion and increased surfactant aggregate ratios compared with controls. Spontaneously breathing injured animals had aggregate conversion and aggregate ratios that were not significantly different from controls. In vitro aggregate conversion was slower for LA obtained from injured animals compared with normal animals. We conclude that the mechanical stress of mechanical ventilation results in increased aggregate conversion and aggregate ratios. Furthermore, in vitro conversion of isolated LA does not necessarily reflect the conversion of aggregates within the alveoli.

Animals↗
PubMed1997

Ventilation strategies affect surfactant aggregate conversion in acute lung injury.

This study evaluated the effects of varying tidal volumes (VT) and positive end-expiratory pressure (PEEP) levels on surfactant aggregate conversion and lung function in an animal model of lung injury induced by N-nitroso-N-methylurethane. Lung-injured adult rabbits were initially ventilated using a VT of 10 ml/kg (VT10), a respiratory rate of 30 breaths/min (RR30), and a PEEP of 3.5 cm H2O. A trace dose of radiolabeled rabbit large surfactant aggregates was instilled after the onset of ventilation, and animals were then ventilated at different ventilator settings for 1 h. Ventilation strategies involving a lower VT (VT5, RR60) resulted in significantly superior oxygenation and lower surfactant aggregate conversion rates than strategies involving a higher VT ([VT10, RR30], [VT15, RR20], p < 0.05). Increasing the PEEP level to 8.0 cm H2O improved oxygenation, but it was sustained only with a low VT (VT5, RR60), and deteriorated with a high VT (VT10, RR30). Varying VT but not PEEP levels resulted in significant changes in surfactant aggregate conversion. We conclude that increased surfactant aggregate conversion resulting from suboptimal ventilation of injured lungs may play an important role in the pathophysiology of ventilation-induced lung dysfunction in acute lung injury.

Animals↗
PubMed1997

Dobutamine echocardiography for prediction of ischemic events in heart transplant recipients.

The purpose of this study was to assess the use of dobutamine stress echocardiography in predicting cardiac events in heart transplant recipients. Dobutamine echocardiography was performed in 63 consecutive heart transplant recipients, 52 males and 11 females ranging in age from 12 to 77 years (mean 54), undergoing routine yearly evaluation. Twenty-one patients had abnormal wall motion at baseline or during dobutamine infusion. Over a mean follow-up of 8 months (range 4 to 14), there were six major cardiac events: five occurred among patients with abnormal echocardiography study results; only one event occurred in a patient with a normal echocardiography result. These data suggest that normal wall motion during dobutamine echocardiography identifies a subset of heart transplant recipients at low risk for development of cardiac events, whereas an abnormal study result serves as an important predictor of subsequent cardiac events.

Adolescent↗
PubMed1996

Surfactant-associated protein A is important for maintaining surfactant large-aggregate forms during surface-area cycling.

Alveolar surfactant can be separated into two major subfractions, the large surfactant aggregates (LAs) and the small surfactant aggregates (SAs). The surface-active LAs are the metabolic precursors of the inactive SAs. This conversion of LAs into SAs can be studied in vitro using a technique called surface-area cycling. We have utilized this technique to examine the effect of trypsin on aggregate conversion. Our results show that trypsin increases the conversion of LAs into SAs in a concentration- and time-dependent manner. Immunoblot analysis revealed that surfactant-associated Protein A (SP-A) was the main target of trypsin. To examine further the role of SP-A in aggregate conversion, we tested the effect of Ca2+ and mannan on this process. The absence of Ca2+ (l mM EDTA) and the presence of mannan both increased the formation of SAs. Electron microscopy revealed that highly organized multilamellar and tubular myelin structures were present in samples that converted slowly to SAs. We concluded that SP-A is important for maintaining LA forms during surface-area cycling by stabilizing tubular myelin and multilamellar structures.

Animals↗
PubMed1996

Echocardiographic assessment of wall motion in ST-segment alternans during coronary angioplasty.

ST alternans occurs in the setting of severe and extensive myocardial ischemia. In this particular case, ST alternans occurred well after the onset of ischemia-induced left ventricular dysfunction. There is no echocardiographic evidence of beat-to-beat variation in contractility to correspond to this ST-segment phenomenon. Further studies of left ventricular function during ST alternans in patients are needed to determine whether this finding applies to all patients with ischemic heart disease.

Angioplasty, Balloon, Coronary↗