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Biomedical subjects

R A Levine

Publications and source records attributed to R A Levine.

At least 19 recordsLinked to original sources

Three-dimensional echocardiography: techniques and applications.

Current echocardiographic devices provide only 2-dimensional views of the heart. To appreciate 3-dimensional structural relations, therefore, requires mental reconstruction of 2-dimensional views by an experienced observer. Our ability to answer new questions about the heart could be increased if 2-dimensional images could be combined to display 3-dimensional relations. Such 3-dimensional reconstruction would permit analysis of structures of unknown or complex shape and the noninvasive quantification of cardiac chamber size and function without making geometric assumptions. To overcome previous limitations, mechanisms have been developed for automated integration of images and positional data during routine echocardiographic scanning, thereby greatly enhancing the efficiency and application of image reconstruction. Refining the diagnosis of mitral valve prolapse has presented a uniquely 3-dimensional problem requiring information previously unavailable from the 2-dimensional technique. To date, 3-dimensional studies have demonstrated that the mitral valve is saddle-shaped in systole, so that apparent superior leaflet displacement in the mediolateral 4-chamber view, often seen in otherwise normal individuals, lies entirely within the bounds defined by the mitral annulus and occurs without leaflet distortion or actual displacement above the entire mitral valve. Other applications of 3-dimensional image reconstruction include calculation of ventricular volume and ejection fraction by transthoracic or transesophageal scanning without geometric assumptions; improving the standardization and accuracy of 2-dimensional measurements by improving spatial appreciation; and 3-dimensional reconstruction of vascular walls to guide interventions. In the future, systems for acquiring multiple views more rapidly by parallel processing and improving endocardial border extraction should allow more routine application of 3-dimensional methods as the next stage in the evolution of cardiac ultrasound, thereby expanding the range of questions that can be answered. Achieving these goals will depend, in large measure, on persistence in developing the necessary technology.

Echocardiography

Papillary muscle traction in mitral valve prolapse: quantitation by two-dimensional echocardiography.

Previous angiographic observations in patients with mitral valve prolapse have suggested that superior leaflet displacement results in abnormal superior tension on the papillary muscle tips that causes their superior traction or displacement. It has further been postulated that such tension can potentially affect the mechanical and electrophysiologic function of the left ventricle. The purpose of this study was to confirm and quantitate this phenomenon noninvasively by using two-dimensional echocardiography to determine whether superior displacement of the papillary muscle tips occurs and its relation to the degree of mitral leaflet displacement. Directed echocardiographic examination of the papillary muscles and mitral anulus was carried out in a series of patients with classic mitral valve prolapse and results were compared with those in a group of normal control subjects. Distance from the anulus to the papillary muscle tip was measured both in early and at peak ventricular systole. In normal subjects, this distance did not change significantly through systole, whereas in the patient group it decreased, corresponding to a superior displacement of the papillary muscle tips toward the anulus in systole (8.5 +/- 2.6 vs. 0.8 +/- 0.7 mm; p less than 0.0001). This superior papillary muscle motion paralleled the superior displacement of the leaflets in individual patients (y = 1.0x + 0.8; r = 0.93) and followed a similar time course.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Quantification of mitral regurgitation with the proximal flow convergence method: a clinical study.

Accurate quantitation of valvular incompetence remains an important goal in clinical cardiology. It has been shown previously that when color flow Doppler mapping is used, simple measurements of apparent jet size do not correlate closely with regurgitant flow rate and regurgitant fraction. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Flow rate Q can be calculated as Q = 2 pi r2v(a), where v(a) is the aliasing velocity at a distance r from the orifice. In 54 patients (43 with sinus rhythm and 11 with atrial fibrillation) who had at least mild mitral regurgitation according to semiquantitative assessment, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated with the proximal flow convergence method and compared with values that were obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (Vr) as calculated by the proximal flow convergence method correlated very closely with values that were obtained by the Doppler two-dimensional method, with r = 0.93 (y = 0.95x + 0.55) and delta Vr = -0.3 +/- 4.0 cm3. Regurgitant flow rates (Q) as calculated by both methods showed a similar correlation: r = 0.93 (y = 0.95x + 54) and delta Q = -34 +/- 284 cm3/min. The correlation for regurgitant fraction (RF) as calculated by both techniques showed r = 0.89 (y = 0.98x + 0.006) and delta RF = -0.005 +/- 0.06. All correlations were slightly better for the group of patients with sinus rhythm than for the study group of patients with atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation.

The isovolumic relaxation time (IVRT) is an important noninvasive index of left ventricular diastolic function. Despite its widespread use, however, the IVRT has not been related analytically to invasive parameters of ventricular function. Establishing such a relationship would make the IVRT more useful by itself and perhaps allow it to be combined more precisely with other noninvasive parameters of ventricular filling. The purpose of this study was to validate such a quantitative relationship. Assuming isovolumic relaxation to be a monoexponential decay of ventricular pressure (pv) to a zero-pressure asymptote, it was postulated that the time interval from aortic valve closure (when pv = p(o)) until mitral valve opening (when pv = left atrial pressure, pA) would be given analytically by IVRT = tau[log(p(o))-log(pA)], where tau is the time constant of isovolumic relaxation and log is to the base e. To test this hypothesis we analyzed data from six canine experiments in which ventricular preload and afterload were controlled nonpharmacologically. In addition, tau was adjusted with the use of beta-adrenergic blockade and calcium infusion, as well as with hypothermia. In each experiment data were collected before and after the surgical formation of mitral stenosis, performed to permit the study of a wide range of left atrial pressures. High-fidelity left atrial, left ventricular, and aortic root pressures were digitized, the IVRT was measured from the aortic dicrotic notch until the left atrioventricular pressure crossover point, and tau was calculated by nonlinear least-squares regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of repair surface design, repair material, and processing method on the transverse strength of repaired acrylic denture resin.

The transverse strengths of blocks of denture base acrylic resin repaired with autopolymerizing monomer and polymer and autopolymerizing monomer and heat-cured polymer were measured with a three-point bending test. Three repair joints were studied: butt, round, and 45-degree bevel. Three processing methods were used: bench cure, hydroflask with hot water for 10 minutes, and hydroflask with hot water for 30 minutes. The strengths of repairs made with round and 45-degree bevel joint designs were similar and significantly greater than those with a butt joint design. The strengths of repairs processed in a hydroflask for 10 minutes and 30 minutes were similar and significantly greater than those cured on the bench top. There was no difference in the strength of repairs made with autopolymerizing monomer and polymer and autopolymerizing monomer and heat-cured polymer.

Acrylic Resins

Insights from in-vitro flow visualization into the mechanism of systolic anterior motion of the mitral valve in hypertrophic cardiomyopathy under steady flow conditions.

Hypertrophic obstructive cardiomyopathy is a heart disease characterized by a thickened interventricular septum which narrows the left ventricular outflow tract, and by systolic anterior motion (SAM) of the mitral valve which can contact the septum and create dynamic subaortic obstruction. The most common explanation for SAM has been the Venturi mechanism which postulates that septal hypertrophy, by narrowing the outflow tract, produces high velocities and thus low pressure between the mitral valve and the septum, causing the valve leaflets to move anteriorly. This hypothesis, however, fails to explain why SAM often begins early in systole, when outflow tract velocities are low or negligible or why it may occur in the absence of septal hypertrophy. The goal of this study was therefore to investigate an alternative hypothesis in which structural abnormalities of the papillary muscles act as a primary cause of SAM by altering valve restraint and thereby changing the geometry of the closed mitral apparatus and its relationship to the surrounding flow field. In order to test this hypothesis, an in vitro model of the left ventricle which included an explanted human mitral valve with intact chords and papillary muscle apparatus was constructed. Flow visualization was used to observe the ventricular flow field and the mitral valve geometry. Displacing the papillary muscles anteriorly and closer to each other, as observed clinically in patients with cardiomyopathy and obstruction produced SAM in the absence of septal hypertrophy. Flow could be seen impacting on the upstream (posterior) surface of the leaflets; such flow is capable of producing form drag forces which can initiate and maintain SAM.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Hypertrophic

Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation.

BACKGROUND: The time constant of isovolumic relaxation (tau) is an important parameter of ventricular diastolic function, but the need for invasive measurement with high-fidelity catheters has limited its use in general clinical cardiology. The Doppler mitral regurgitant velocity spectrum can be used to estimate left ventricular (LV) pressure throughout systole and may provide a new noninvasive method for estimating tau. METHODS AND RESULTS: Mitral regurgitation was produced in nine dogs, and ventricular relaxation was adjusted pharmacologically and with hypothermia. High-fidelity ventricular pressures were recorded, and tau was calculated from these hemodynamic data (tau H) assuming a zero-pressure asymptote. Continuous-wave mitral regurgitant velocity profiles were obtained, and the ventriculo-atrial (VA) pressure gradient was calculated by the simplified Bernoulli equation; tau was calculated from the Doppler data from the time of maximal negative dP/dt until LV-LA pressure crossover. Three methods were used to correct the Doppler VA gradient to better approximate the LV pressure before calculating tau: 1) adding actual LA V wave pressure (to yield tau LA); 2) adding 10 mm Hg (tau 10); and 3) no adjustment at all (actual VA gradient used to calculate tau 0). The agreement between tau H and the three Doppler estimates of tau was assessed by linear regression and by the mean and standard deviation of the error between the measurements (delta tau). the measurements (delta tau). tau H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of tau seriously underestimated tau H: tau 0 = 0.30 tau H + 9.4, r = 0.79, delta tau = -35 +/- 18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: tau LA = 0.92 tau H + 7.6, r = 0.95, delta tau = 2 +/- 7 msec. Addition of a fixed LA pressure estimate of 10 mm Hg to the VA gradient yielded an estimate that was almost as good: tau 10 = 0.89 tau H + 4.9, r = 0.88, delta tau = -2 +/- 12 msec. In general, tau was overestimated when actual LA pressure was below this assumed value, and vice versa. Numerical analysis demonstrated that assuming LA pressure to be 10 mm Hg should yield estimates of tau accurate to +/- 15% between true LA pressures of 5 and 20 mm Hg. CONCLUSIONS: This study demonstrates that the Doppler mitral regurgitant velocity profile can be used to provide a direct and noninvasive measurement of tau. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of tau in clinical and research settings, leading to a better understanding of the role of impaired ventricular relaxation in diastolic dysfunction and the effect of therapeutic interventions.

Animals

Impact of finite orifice size on proximal flow convergence. Implications for Doppler quantification of valvular regurgitation.

Analysis of velocity acceleration proximal to a regurgitant valve has been proposed as a method to quantify the regurgitant flow rate (Qo). Previous work has assumed inviscid flow through an infinitesimal orifice, predicting hemispheric isovelocity shells, with calculated flow rate given by Qc = 2 pi rN2vN, where vN is user-selected velocity of interest and rN is the distance from that velocity to the orifice. To validate this approach more rigorously and investigate the impact of finite orifice size on the assumption of hemispheric symmetry, numerical and in vitro modeling was used. Finite-difference modeling demonstrated hemispheric shape for contours more than two orifice diameters from the orifice. More proximal than this (where the measured velocity vN exceeded 3% of the orifice velocity vo), flow was progressively underestimated, with a proportional error delta Q/Qo nearly identical to the ratio of contour velocity to orifice velocity, vN/vo. For the in vitro investigations, flow rates from 4.3 to 150 cm3/sec through 0.3 and 1.0 cm2 circular orifices were imaged with color Doppler with aliasing velocities from 19 to 36 cm/sec. Overall, the calculated flow (assuming hemispheric symmetry) correlated well with the true flow, Qc = 0.88Qo-7.82 (r = 0.945, SD = 12.2 cm3/sec, p less than 0.0001, n = 48), but progressively underestimated flow when the vN approached the orifice velocity vo. Applying a correction factor predicted by the numerical modeling, delta Q was improved from -13.81 +/- 13.01 cm3/sec (mean +/- SD) to +1.54 +/- 5.67 cm3/sec.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Circulation

A rat alveolar type II cell line developed by adenovirus 12SE1A gene transfer.

The regulation of pulmonary alveolar type II cell proliferation and differentiation is poorly understood and has been difficult to study, in part due to lack of proliferation, cellular heterogeneity, and phenotypic instability of type II cells in primary culture. To develop a stable population of homogeneous cells capable of proliferation, we transfected type II cells isolated from the lungs of neonatal rats with an immortalizing oncogene, adenovirus 12SE1A, using a retroviral vector. Individual clones were isolated, screened for cytokeratin expression, and further characterized. One of the 12SE1A expressing clones, E1A-T2, has epithelial features such as cytokeratin expression and tight junctions, and coexpresses vimentin. E1A-T2 rapidly proliferate when grown in 10% fetal bovine serum, and slow their growth at confluence. A labeling index of greater than 90% during a 24-h pulse of [3H]thymidine reflects a uniform population of proliferating cells. E1A-T2 can be grown and passed in 0.4% fetal bovine serum, suggesting the production of an autocrine growth factor(s). The type II cell Maclura pomifera agglutinin (MPA)-binding glycoprotein, MPA-gp200, appears to be expressed in an incompletely glycosylated form, whereas other features of differentiated type II cells, such as lamellar bodies, surfactant protein A, and a high percentage of saturated phosphatidylcholine, are absent. Homogeneous, clonally derived type II cell lines, such as E1A-T2 may retain sufficient type II cell features of interest to test new hypotheses relating to cell proliferation and differentiation otherwise not feasible using primary cultures of type II cells.

Adenoviridae

Preservation of hearing and facial nerve function in resection of acoustic neuroma.

The surgical results in 78 recent cases of total removal of unilateral acoustic neuroma in which an attempt was made to preserve cochlear function have been added to the authors' previous series of 66 cases to evaluate the factors influencing the ability to preserve useful hearing. Useful hearing was defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%. Analysis using a logistic regression model showed that certain preoperative clinical parameters such as tumor size, speech discrimination score, and gender were significantly correlated with hearing outcome. Favorable outcome was significantly correlated with smaller tumor size, higher preoperative speech discrimination score, and male sex. From this data, an explicit formula was devised for predicting hearing outcome for an individual patient. In four cases with useful hearing preserved, there was improvement of greater than 15 percentage points in speech discrimination scores. While preoperative auditory brainstem responses were not predictive of hearing preservation, monitoring of intraoperative auditory evoked potentials was predictive of hearing outcome in selected cases. Specifically, when wave V was unchanged at the end of the operation, even if it may have been transiently lost during surgery, useful hearing was invariably preserved.

Audiometry, Evoked Response

Long-term hearing results in patients after surgical removal of acoustic tumors with hearing preservation.

Long-term hearing results are described in 18 patients after suboccipital removal of unilateral acoustic neurinomas. Follow-up ranged from 3.4 to 10.4 years with a mean of 5.4 years. Fourteen patients (78%) experienced no significant decline in long-term hearing. Four patients (22%) experienced a significant decline in long-term hearing as defined by a drop in pure-tone average (0.5, 1, and 2 kHz), or a significant decline in Speech Discrimination Scores (SDS). Changes in hearing did not correlate with tumor size, preoperative hearing, intraoperative change in hearing, the interval between initial symptoms and surgery, sex, or age.

Audiometry, Evoked Response

Human carbonyl and aldose reductases: new catalytic functions in tetrahydrobiopterin biosynthesis.

New catalytic functions of human carbonyl- and aldose reductase in tetrahydrobiopterin biosynthesis are proposed. 6-Pyruvoyl tetrahydropterin, an intermediate in the biosynthesis of tetrahydrobiopterin, was converted to 6-lactoyl tetrahydropterin and 1'-hydroxy-2'-oxopropyl tetrahydropterin by carbonyl reductase under anaerobic condition. 1'-Hydroxy-2'-oxopropyl tetrahydropterin was subsequently metabolized to tetrahydrobiopterin by aldose reductase. Based on these results alternative pathways for the synthesis of tetrahydrobiopterin in patients with genetic defects of sepiapterin reductase are suggested.

Alcohol Oxidoreductases

Hearing loss and pneumococcal meningitis: an animal model.

Clinical studies of predisposing factors in the development of hearing loss secondary to bacterial meningitis have produced conflicting results. An animal model of meningogenic labyrinthitis was developed for more precise study of these parameters. Rabbits were inoculated intrathecally with 10(5) pneumococci to induce meningitis. Hearing thresholds were measured using auditory-evoked responses to 1 kHz, 10 kHz, and click stimuli before infection and every 12 hours thereafter. Profound deafness occurred in all subjects at an average of 48 hours following infection. The incidence and severity of hearing loss was strongly correlated with the duration of meningitis. Temporal bone histology revealed acute inflammation of all perilymphatic spaces including the cochlear aqueduct. This model demonstrated that the risk and severity of hearing loss increase with the duration of meningitis and suggested that the cochlear aqueduct is an anatomic pathway for the extension of infection from the cerebrospinal fluid to the cochlea. The implications for therapy in humans is discussed.

Acoustic Stimulation

Aspirin induces morphological transformation to the secretory state in isolated rabbit parietal cells.

The morphological response of rabbit parietal cells to aspirin was evaluated by grading several ultra-structural features including the extent of the tubulovesicular system, intracellular secretory canaliculi, and microvilli. After exposure of isolated parietal cells and gastric glands to aspirin or histamine, there was an approximately twofold increase in the ratio of secretory to nonsecretory parietal cells, and depletion of extracellular Ca2+ abolished the aspirin-induced morphological changes. Morphometry in parietal cells showed that aspirin induced a sixfold increase in secretory canalicular membrane elaboration. Aspirin potentiated histamine-induced parietal cell respiration and aminopyrine uptake ratio but did not increase basal respiration or aminopyrine uptake, suggesting an apparent dissociation from aspirin-induced morphological changes.

Animals

Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells. Investigation of the mechanisms of action.

The effects of nonsalicylate nonsteroidal antiinflammatory drugs on acid secretion were studied in isolated rabbit parietal cells. Indomethacin, naproxen, and carprofen (10(-6)-10(-4) mol/L) potentiated histamine-, forskolin-, 3-isobutyl-1-methylxanthine-, and dibutyryl cyclic adenosine monophosphate-stimulated acid secretion without affecting basal acid secretion. This augmentation of secretagogue-stimulated acid secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium or in the presence of the calcium antagonist lanthanum chloride. Potentiation was independent of the H2 and muscarinic receptors and did not appear to involve guanine nucleotide regulatory proteins. Proton pump activity was unaffected by indomethacin. Furthermore, nonsteroidal antiinflammatory drugs increased calcium efflux through the plasma membrane, as measured by calcium 45, and decreased endogenous prostaglandin E2 content. Exogenous dimethyl prostaglandin E2 inhibited the potentiating effect of these drugs on histamine-stimulated but apparently not on dibutyryl cyclic adenosine monophosphate-stimulated acid secretion. The data indicate that nonsalicylate nonsteroidal antiinflammatory drugs interacted at a postreceptor site between adenylate cyclase and the proton pump. The potentiating effects of these drugs were regulated by calcium and possibly modulated by prostanoids.

Animals