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Biomedical subjects

J F Lewis

Publications and source records attributed to J F Lewis.

At least 19 recordsLinked to original sources
PubMed1992

Platelet-activating factor antagonists decrease lung protein leak in preterm ventilated rabbits.

OBJECTIVE: The preterm ventilated lung is characterized by an increased protein leak from the pulmonary vascular spaces into the air spaces, which interferes with lung function and plays a role in neonatal respiratory distress syndrome. To investigate the role of platelet-activating factor in this process, platelet-activating factor antagonists were given to preterm ventilated rabbits. STUDY DESIGN: New Zealand White rabbits were delivered on day 28 of 31 days' gestation. Each rabbit pup received saline solution or one of two platelet-activating factor antagonists and were ventilated for 30 minutes with measurement of compliance, surfactant pool size, and protein leak into and out of the lung. Statistical analysis was performed with analysis of variance followed by Student-Newman-Keuls correction for multiple comparisons. RESULTS: There were no differences in lung compliance, surfactant pool size, or protein leak out of the air spaces among any of the groups. Treatment with the platelet-activating factor antagonists decreased the protein leak into the air spaces by greater than 50% and into the lung as a whole by 40% (p less than 0.01). CONCLUSION: Platelet-activating factor plays a role in the protein leak seen in the preterm lung, which contributes to neonatal respiratory distress syndrome.

Animals↗
PubMed1992

Usefulness of Doppler echocardiographic assessment of diastolic filling in distinguishing "athlete's heart" from hypertrophic cardiomyopathy.

OBJECTIVE: In some athletes with a substantial increase in left ventricular wall thickness, it may be difficult to distinguish with certainty physiological hypertrophy due to athletic training from hypertrophic cardiomyopathy. The purpose of the present investigation was to determine whether assessment of left ventricular filling could differentiate between these two conditions. DESIGN: Doppler echocardiography was used to obtain transmitral flow velocity waveforms from which indices of left ventricular diastolic filling were measured. Normal values were from 35 previously studied control subjects. SETTING: Athletes were selected mostly from the Institute of Sports Science (Rome, Italy), and patients with hypertrophic cardiomyopathy were studied at the National Institutes of Health (Bethesda, Maryland). PARTICIPANTS: The athlete group comprised 16 young competitive athletes with an increase in left ventricular wall thickness (range 13-16 mm; mean 14). For comparison, 12 symptom free patients with non-obstructive hypertrophic cardiomyopathy were selected because their ages and degree of hypertrophy were similar to those of the athletes. RESULTS: In the athlete group, values for deceleration of flow velocity in early diastole, peak early and late diastolic flow velocities, and their ratio were not significantly different from those obtained in untrained normal subjects; furthermore, Doppler diastolic indices were normal in each of the 16 athletes. Conversely, in patients with hypertrophic cardiomyopathy, mean values for Doppler diastolic indices were significantly different from both normal subjects and athletics (p = 0.01 to 0.003), and one or more indices were abnormal in 10 (83%) of the 12 patients. CONCLUSIONS: Doppler echocardiographic indices of left ventricular filling may aid in distinguishing between pronounced physiological hypertrophy due to athletic training and pathological hypertrophy associated with hypertrophic cardiomyopathy.

Adaptation, Physiological↗
PubMed1992

Surfactant protein A metabolism in preterm ventilated lambs.

Surfactant protein A (SP-A) metabolism was studied in vivo in 33 preterm ventilated lambs at 138 +/- 1 days gestational age by measuring recoveries of exogenously administered surfactant containing both radiolabeled SP-A and labeled saturated phosphatidylcholine (Sat PC) given via the trachea at birth. Endogenously secreted SP-A was also labeled with [35S]methionine and followed over 24 h. The exogenously labeled SP-A left the alveolar pool more rapidly than did Sat PC over the first 5 h of life (P less than 0.05), and both exogenously labeled SP-A and Sat PC were detected within lamellar bodies by 2 h, indicating uptake from the airspaces. The quantity of SP-A in alveolar washes increased about twofold from birth to 5 h of age, whereas alveolar Sat PC pools were constant over 24 h. The SP-A endogenously labeled with [35S]methionine was recovered at highest specific activities in the alveolar washes at 10 and 45 min after birth with no labeled SP-A detectable in lamellar body fractions until 2 h. The curve for endogenous SP-A labeling of lamellar bodies was similar to that for exogenous labeling, indicating that SP-A was initially secreted by a pathway independent of lamellar bodies with subsequent SP-A labeling of lamellar bodies. The kinetics of SP-A metabolism were very different than for Sat PC in preterm lambs.

Animals↗
PubMed1992

Metabolism of exogenously administered surfactant in the acutely injured lungs of adult rabbits.

Acute lung injury was induced in adult rabbits with a subcutaneous injection of N-nitro-so-N-methylurethane (NNNMU). Clearance of saturated phosphatidylcholine (Sat.PC) from a treatment dose of exogenous surfactant (100 mg/kg) in the injured lungs of these rabbits was similar to normal, control rabbits when measured 24 h after treatment. However, total Sat.PC pool sizes in both the alveolar wash and total lung at this time point were significantly lower for the injured lungs than for the control lungs (p less than 0.05), implying altered endogenous surfactant metabolism in response to surfactant treatment in the injured animals. Although both injured and control animals had comparable ratios of small to large surfactant aggregates, as measured by differential centrifugation of alveolar wash 5 min after treatment, by 24 h this ratio had increased 5-fold in the control animals and remained unchanged in the injured animals. This indicated diminished conversion of large surfactant aggregates to the smaller forms in lung injury. In vivo functional studies of these aggregates were performed by intratracheal injection into surfactant-deficient preterm rabbits. Large aggregates from normal adult rabbits given surfactant had superior functional properties than did the surfactant used for treatment alone, which in turn was better than large aggregates isolated from NNNMU-injured rabbits treated with surfactant. This indicates that the alveolar environment influenced the function of the exogenously administered surfactant differently in normal and injured rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Lung albumin recovery in surfactant-treated preterm ventilated lambs.

Preterm ventilated animals and infants with respiratory distress syndrome (RDS) develop proteinaceous alveolar edema. To study the effect of postnatal age on intravascular radiolabeled albumin accumulation into lungs, preterm lambs at 132 days gestational age were ventilated after treatment with sheep surfactant or cow surfactant extract for periods as long as 24 h. Lambs not treated with surfactant were studied for only 5 h because of severe respiratory failure. All lambs were given radiolabeled albumin by intravascular injection 1 h before they were killed, and the net recovery of the labeled albumin was measured in the lung tissue and air space as quantified by alveolar lavage. Net 1-h radiolabeled albumin recoveries in the lungs decreased from 5 to 6% soon after birth to 0.9% at 24 h in the surfactant-treated groups (p less than 0.01). At 3 h there was less labeled albumin recovery by alveolar lavages in lambs treated with sheep surfactant than in control lambs and lambs treated with cow surfactant extract (p less than 0.05). Protein in alveolar washes from lambs treated with cow surfactant extract exceeded that in lambs treated with sheep surfactant at 3 h (p less than 0.05), but protein recoveries had decreased to similar values by 24 h, indicating a net clearance of air-space protein. These studies demonstrate a sixfold decrease in net albumin accumulation from birth to 24 h of age despite continued ventilation and oxygen exposure of the premature lamb lungs.

Animals↗
PubMed1992

Considerations for racial differences in the athlete's heart.

Exercise training is associated with changes in left ventricular morphology commonly referred to as the athlete's heart. The magnitude of these changes appears to be due in part to the type, intensity, and duration of training. Certain athletes develop more marked alterations in left ventricular morphology, however. This raises the consideration of whether the cardiac response to athletic training may also be influenced by genetic or racial factors.

Adaptation, Physiological↗
PubMed1992

Cardiovascular consequences of the aging process.

The normal aging process is associated with a variety of cardiovascular changes. Recognition of these alterations in cardiovascular structure and function that occur in the aging population is essential for assessment of cardiac disease in older patients. For example, a number of studies show that aging is associated with increasing left ventricular wall thickness and mass. However, these changes are gradual and relatively mild, and absolute wall thickness measurements in individual elderly subjects rarely exceed generally accepted normal values. Parameters of left ventricular systolic function (either under basal conditions or with exercise) change little with aging. In contrast, apparent alterations in left ventricular diastolic filling patterns often accompany advancing age. Investigations in normal elderly subjects have shown that the early filling phase is prolonged, and the rate and volume (as well as flow-velocity) of rapid filling are decreased. These alterations are associated with a compensatory increase in late diastolic filling with atrial systole. The aging changes in left ventricular filling identified by noninvasive tests (such as Doppler echocardiography or radionuclide angiography) may mimic in appearance those observed in a number of cardiovascular diseases, making interpretation of their clinical significance difficult in an elderly population.

Aging↗
PubMed1991

Hypertrophic cardiomyopathy characterized by marked hypertrophy of the posterior left ventricular free wall: significance and clinical implications.

This report describes a subgroup of 17 patients with hypertrophic cardiomyopathy and an unusual and distinctive pattern of left ventricular hypertrophy characterized on echocardiography by marked thickening of the posterior left ventricular free wall and virtually normal or only modestly increased ventricular septal thickness. This distribution of hypertrophy often created a distinctive pattern of "inverted" asymmetry of the posterior wall relative to the septum. The thickness of the posterior wall was 20 to 42 mm (mean 25), while that of the basal ventricular septum was only 12 to 24 mm (mean 17). The left ventricular outflow tract was narrowed because of anterior displacement of the mitral valve within the small left ventricular cavity. Systolic anterior motion of the mitral valve was present in 16 of the 17 patients. The patients ranged in age from 13 to 54 years (mean 31) at most recent evaluation; most (11 of 17, 65%) were severely symptomatic and had experienced important symptoms early in life (before age 40). The condition of only 4 of these 11 patients improved with medical therapy over an average follow-up period of 9 years; however, 6 of the 7 patients who had unsuccessful medical treatment and underwent operation with mitral valve replacement (5 patients) or ventricular septal myotomy-myectomy (1 patient) experienced symptomatic benefit from surgery. The subgroup of patients described in this report underscores the morphologic and clinical diversity that exists within the overall disease spectrum of hypertrophic cardiomyopathy. Characteristically, the patients were young, severely symptomatic and demonstrated evidence of outflow obstruction and an "inverted" asymmetric pattern of posterior free wall left ventricular hypertrophy. (ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Left ventricular diastolic filling abnormalities identified by Doppler echocardiography in asymptomatic patients with sickle cell anemia.

To determine whether left ventricular diastolic abnormalities are an early feature of sickle cell anemia, indexes of diastolic filling were obtained with pulsed Doppler echocardiography in 30 consecutive patients with this disease (mean age 29 years; range 19 to 39) who had not experienced symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those in 30 normal control subjects of similar ages. Seventeen (57%) of the 30 patients with sickle cell anemia had evidence of abnormal left ventricular diastolic filling. Six of these 17 patients had a Doppler pattern consistent with "restrictive" filling, characterized by reduced early diastolic deceleration time (less than 110 ms) or an increased rate of decline of early flow velocity (EF slope greater than 7.4 m/s2), or both, as well as decreased late diastolic velocity-time integral (2.6 +/- 0.7 vs. 3.4 +/- 0.8 cm in normal subjects; p less than 0.05). Another 11 patients showed a Doppler waveform consistent with impaired relaxation, characterized by prolonged deceleration time (greater than 166 ms) or reduced EF slope (less than 3.8 m/s2), as well as increased late diastolic velocity-time integral (4.0 +/- 0.5 vs. 3.4 +/- 0.8 cm in normal subjects; p = 0.03). This Doppler echocardiographic analysis demonstrates that left ventricular diastolic filling patterns are altered in patients with sickle cell anemia and that these diastolic abnormalities may be present in the absence of symptoms of heart failure. These abnormal patterns suggest an intrinsic myocardial abnormality in patients with sickle anemia and may prove to be early markers of cardiac disease.

Adult↗
PubMed1991

Dose effects of antenatal corticosteroids for induction of lung maturation in preterm rabbits.

Dose-response effects of corticosteroids were investigated in the preterm rabbit. Pregnant rabbits were given two doses of 0.01, 0.03, or 0.1 mg of betamethasone per kilogram every 24 hours, beginning on day 25 of gestation. Saline solution was used in a comparison treatment group. Half of the newborn rabbits received supplemental surfactant therapy after delivery via cesarean section on day 27, and all were ventilated on a ventilator-plethysmograph system for 30 minutes. The 0.01 and 0.03 mg/kg regimens had no effect on birth weight or lung function. The 0.1 mg/kg regimen resulted in fetal growth retardation and improved ventilatory measurements, gas exchange, and decreased protein accumulation in the lung, without increasing surfactant pool size. The induction of lung maturation by corticosteroids has multiple targets in the developing lung and does not exhibit a linear dose response.

Animals↗
PubMed1991

Aerosolized surfactant treatment of preterm lambs.

To evaluate the potential for aerosolized surfactant treatments of surfactant deficiency, twin lamb fetuses were delivered at 130-132 days gestational age and received nebulized natural surfactant (Neb NS), nebulized Survanta (Neb Surv), tracheally instilled natural surfactant (Inst NS), or nebulized saline (Neb Saline). Neb NS and Neb Surv groups had significant increases in ventilatory efficiency index and dynamic compliance values (P less than 0.05). Both groups also had pressure-volume curves that were comparable to the Inst NS group. The Neb Saline control group had deterioration of the ventilation efficiency index and dynamic compliance values over time as well as pressure-volume curves that demonstrated smaller lung volumes compared with all three surfactant-treated groups (P less than 0.01). Delivery of aerosolized surfactant to the lung was only approximately 2 mg lipid/kg for the nebulized groups, a dose one-twentieth of that previously noted to be effective in instillation protocols. Distribution histograms of the aerosolized surfactant-treated groups differed from the instilled animals as there was more deposition in the right upper lobes and tracheae in the nebulized groups compared with the instilled group (P less than 0.05). Pulmonary blood flow was not altered by aerosolized surfactant treatment. Administration of aerosolized surfactant to preterm lambs improved lung function at a very low surfactant dose.

Aerosols↗
PubMed1990

Diversity of patterns of hypertrophy in patients with systemic hypertension and marked left ventricular wall thickening.

In selected patients with systemic hypertension it may be difficult to ascertain whether left ventricular (LV) hypertrophy is a secondary end-organ consequence of long-term elevations in blood pressure or, alternatively, a manifestation of a coexistent primary hypertrophic cardiomyopathy. To address this issue and better characterize LV hypertrophy in systemic hypertension, 2-dimensional echocardiography was used to define the patterns of LV hypertrophy in 102 patients with sustained systemic hypertension and marked degrees of wall thickening. Patients ranged in age from 31 to 88 years (mean 61) and were predominantly female (58%); all were black. By selection, each patient had a maximal LV wall thickness of greater than 15 mm (range 16 to 29). Distribution of hypertrophy was judged to be symmetric (i.e., concentric) in most patients (67 of 102, 66%). However, a substantial proportion (35 patients, 34%) demonstrated nonuniform, asymmetric patterns of hypertrophy in which at least 1 segment of the LV wall was at least 1.5 times the thickness of any other. In these 35 patients, the distribution of hypertrophy was similar to that characteristic of the morphologic spectrum of hypertrophic cardiomyopathy, with thickening of portions of both the ventricular septum and free wall in 16 patients, anterior and posterior ventricular septum alone in 11 patients and segmental involvement of only the anterior ventricular septum in 8. Patients with asymmetric patterns of wall thickening did not differ from the patients with symmetric hypertrophy with regard to age, sex or clinical findings. Asymmetric LV hypertrophy appears to represent an important feature of the morphologic spectrum of severe hypertensive heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Altered surfactant function and metabolism in rabbits with acute lung injury.

Lung injury was induced in rabbits with N-nitroso-N-methylurethane (NNNMU), and saturated phosphatidylcholine (Sat PC) pool sizes and phospholipid compositions were measured in alveolar wash subfractions isolated by differential centrifugation (large and small surfactant aggregates). Surfactant metabolism also was studied using intravascular and intratracheal radiolabels. Protein permeability, gas exchange, and compliance were significantly abnormal as lung injury progressed. At peak injury, there was a decrease in the large aggregate Sat PC pool size in alveolar wash accompanied by increased uptake of Sat PC from the air space and increased specific activity of both intravascular and intratracheal radiolabels in lamellar bodies. This was followed by a marked rise in the small aggregate pool size in the alveolar wash and increased secretion of Sat PC into the air spaces. Phospholipid compositions, total phospholipid-to-protein ratios, and in vivo functional studies using a preterm ventilated rabbit model were abnormal for both large and small aggregate surfactant fractions from the lung-injured rabbits. These studies characterize quantitative, qualitative, and functional changes of alveolar wash surfactant subfractions in NNNMU-injured lungs.

Animals↗
PubMed1989

Preparticipation echocardiographic screening for cardiovascular disease in a large, predominantly black population of collegiate athletes.

Sudden death in young competitive athletes is most commonly due to underlying cardiovascular disease. Echocardiography has the potential to identify structural cardiovascular abnormalities, such as hypertrophic cardiomyopathy (HC), that have been incriminated in such events. In this study, echocardiography (2-dimensional and M-mode) was used as a primary screening test to assess 265 Howard University collegiate athletes for cardiovascular disease; 262 (99%) were black. Most athletes (234, 88%) had no definitive echocardiographic evidence of HC or other major cardiovascular diseases, but 30 (11%) had mitral valve prolapse, and 1 other athlete had a small atrial septal defect. In addition, 4 athletes were identified as having mild systemic hypertension. Most athletes (236 of 265) showed normal left ventricular wall thickness of less than or equal to 12 mm, but an important minority (29, 11%) had maximal ventricular septal thicknesses of greater than or equal to 13 mm that could not always be distinguished (by morphology alone) from mild anatomic expressions of nonobstructive HC. Based on this experience, preparticipation athletic screening using echocardiography as the primary test does not appear to be justified on a cost-effective basis. In addition, the substantial minority of subjects with increased wall thickness made clinical interpretation of the echocardiographic findings difficult in individual athletes.

Adult↗
PubMed1989

Elderly patients with hypertrophic cardiomyopathy: a subset with distinctive left ventricular morphology and progressive clinical course late in life.

This report describes a subgroup of 52 elderly patients with obstructive hypertrophic cardiomyopathy in whom certain clinical and morphologic features differed importantly from those of many other patients with this disease. Ages ranged from 60 to 84 years (mean 69) and 45 [87%] were women. Echocardiographic examination showed a relatively small heart, having only modest ventricular septal hypertrophy associated with marked distortion of left ventricular outflow tract morphology. By virtue of selection, left ventricular outflow tract size at end-diastole was substantially reduced, and anterior displacement of the mitral valve within the left ventricular cavity was particularly marked. Sizable deposits of calcium in the region of the mitral anulus, posterior to the mitral valve, appeared to contribute to the outflow tract narrowing. Systolic anterior motion of the mitral valve was severe (with apposition of the mitral valve and ventricular septum) in 32 patients and more moderate in 20. The mechanism by which systolic contact between the mitral valve and septum occurred in most patients appeared to differ from that observed more typically in many other patients with hypertrophic cardiomyopathy; in most elderly study patients, anterior excursion of the mitral valve leaflets was relatively restricted, and systolic apposition between the mitral valve and septum resulted from a combination of anterior motion of the mitral valve and posterior excursion of the septum. The vast majority (50 of 52) of the patients remained asymptomatic (or only mildly symptomatic) for most of their lives and often did not develop severe and intractable symptoms until the 6th or 7th decade (ages 56 to 81 years; mean 66). Of the 49 patients with at least 1 year follow-up study, only 12 had improvement with pharmacologic therapy; however, 14 of the 18 patients who underwent ventricular septal myotomy-myectomy or mitral valve replacement obtained symptomatic benefit from operation. In conclusion, obstructive hypertrophic cardiomyopathy in many elderly (and predominantly female) patients may assume a distinctive morphologic appearance and a progressive clinical course. This subgroup of patients appears to constitute an important segment of the disease spectrum of hypertrophic cardiomyopathy of cardiac disease in the elderly that previously has not been precisely defined nor fully appreciated.

Biomechanical Phenomena↗
PubMed1987

Hypophosphatemia and respiratory failure: prolonged abnormal energy metabolism demonstrated by nuclear magnetic resonance spectroscopy.

Hypophosphatemia has been shown to cause acute respiratory failure. The mechanism is believed to be due to decreased high-energy substrate availability at the cellular level leading to respiratory muscle dysfunction. However, direct measurement of these substrates has not been previously studied. A patient with hypophosphatemic respiratory failure is described in whom phosphocreatine and pH were continuously monitored using nuclear magnetic resonance spectroscopy. This revealed a defect in muscle metabolism that required several weeks to recover despite prompt correction of the serum phosphate level.

Acute Disease↗
PubMed1985

Effects of transluminal coronary angioplasty on left ventricular systolic and diastolic function at rest and during exercise.

The left ventricular global and regional systolic function, ventricular volumes, and peak diastolic filling rate (PDFR) were studied in 30 patients with coronary artery disease, before and 2 to 5 days after transluminal coronary angioplasty (PTCA), utilizing equilibrium radionuclide angiography at rest and during exercise. At rest, the global ejection fraction (EF) was unchanged before (60 +/- 9%) and after PTCA (62 +/- 10%). During exercise, global EF increased from 59 +/- 11% pre PTCA to 67 +/- 10 post PTCA (p less than 0.001). Twenty-two patients had abnormal EF response to exercise pre PTCA, versus seven post PTCA (p less than 0.001). Improvements in exercise regional EF paralleled the changes in global EF. End-systolic volume was unchanged at rest but decreased significantly with exercise post PTCA (60 +/- 36 ml pre vs 49 +/- 32 ml post PTCA, p less than 0.01). At rest, the PDFR was unchanged post PTCA (2.4 +/- 0.9 end-diastolic volume (EDV)/sec pre vs 2.5 +/- 0.8 EDV/sec post). During exercise, PDFR increased from 2.1 +/- 0.7 EDV/sec pre PTCA to 2.5 +/- 0.7 EDV/sec post PTCA (p less than 0.02). In conclusion, in patients with coronary artery disease, successful PTCA improves global and regional systolic function during exercise. Diastolic function is improved during exercise, a fact not previously demonstrated.

Adult↗