Showing papers by "Robert A. Levine published in 1997"
TL;DR: LV dysfunction without dilatation fails to produce important MR, and functional MR relates strongly to changes in the 3D geometry of the mitral valve attachments at the PM and annular levels, with practical implications for approaches that would restore a more favorable configuration.
Abstract: Background Recent advances in three-dimensional (3D) echocardiography allow us to address uniquely 3D scientific questions, such as the mechanism of functional mitral regurgitation (MR) in patients with left ventricular (LV) dysfunction and its relation to the 3D geometry of mitral leaflet attachments. Competing hypotheses include global LV dysfunction with inadequate leaflet closing force versus geometric distortion of the mitral apparatus by LV dilatation, which increases leaflet tethering and restricts closure. Because geometric changes generally accompany dysfunction, these possibilities have been difficult to separate. Methods and Results We created a model of global LV dysfunction by esmolol and phenylephrine infusion in six dogs, initially with LV expansion limited by increasing pericardial restraint and then with the pericardium opened. The mid-systolic 3D relations of the papillary muscle (PM) tips and mitral valve were reconstructed. Despite severe LV dysfunction (ejection fraction, 18±6%), only...
596 citations
Patent•
24 Nov 1997
TL;DR: In this paper, a method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of target cancer cells and/or hematologic progenitor cells which are known to circulate in blood.
Abstract: A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of target cancer cells and/or hematologic progenitor cells which are known to circulate in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis involves both morphometric and epitopic examination of the blood sample while the blood sample is disposed in a centrifuged blood sampling tube. The epitopic analysis of the presence or absence of cancer cells relies on the detection of epitopes which are known to present only on cancer cells; and the epitopic analysis of the presence or absence of hematologic progenitor cells relies on the detection of epitopes which are known to present only on hematologic progenitor cells. The targeted epitopes on the target cell types are epitopes which are also known to be absent on normal circulating blood cells; and the target cancer cell epitopes are epitopes which are known to be absent on target hematologic progenitor cells. Fluorophors with distinct emissions are coupled with antibodies which are directed against the targeted epitopes. The morphometric analysis is performed by staining the cells in the blood sample with an intracellular stain such as acridine orange which highlights the intracellular cell structure. Both the morphometric and epitopic analyses are preferably performed at or near the platelet layer of the expanded buffy coat in the centrifuged blood sample. The morphometric analysis and/or the epitopic analysis may be performed under magnification both visually and/or photometrically.
96 citations
Journal Article•
TL;DR: Mitral leaflet elongation, by increasing the residual Leaflet length and leaflet mobility, can play an important role in promoting SAM in response to outflow forces, as demonstrated by prospectively altering leaflet length.
Abstract: Background and aims of the study There is growing evidence for mitral leaflet elongation in patients with hypertrophic cardiomyopathy. Such elongation could predispose to systolic anterior motion (SAM) of the mitral valve by increasing leaflet mobility and providing a geometry that promotes this condition. Methods To test this postulate, five porcine mitral valves were studied in a physiologic left heart pulsatile flow duplicator. They were elongated with patches sutured to the basal posterior leaflet (three sizes per valve) or anterior leaflet (basal, middle, or distal). Each geometry was studied with normal papillary muscle position and with anterior and inward displacement, as seen in hypertrophic cardiomyopathy, to shift the leaflets into the outflow stream. Results Four points became clear. 1) Leaflet elongation promoted the development of SAM in response to papillary muscle displacement by creating long overlapping residual leaflets capable of moving anteriorly. 2) Posterior leaflet elongation also promoted SAM by shifting leaflet coaptation anteriorly, with progressive increases in SAM. 3) Basal and mid-anterior leaflet elongation caused SAM with prolapse; distal anterior leaflet elongation created SAM with a mobile flap (leaflet elongation without papillary muscle displacement created prolapse). 4) Residual leaflet length correlated well with total leaflet length (r = 0.87-0.98 for each valve), and the degree of SAM in turn correlated well with residual leaflet length (r = 0.62-0.98 for individual valves). Conclusions Mitral leaflet elongation, by increasing the residual leaflet length and leaflet mobility, can play an important role in promoting SAM in response to outflow forces, as demonstrated by prospectively altering leaflet length. These findings are consistent with recent observations that reducing leaflet redundancy and posterior leaflet height can reduce obstructive SAM following mitral valve repair in patients with mitral valve prolapse and help relieve obstruction in patients with hypertrophic cardiomyopathy and enlarged leaflets.
57 citations
TL;DR: The frequency of true MVP associated with chronic MS is much lower than reported previously and may provide insight into the underlying pathophysiologic process, tending to shorten the chordae tendineae and leaflets to produce stenosis rather than elongate them to produce prolapse.
Abstract: To date, the relation between mitral stenosis (MS) and other associated cardiac valvular lesions has been reported by angiography and surgical pathologic study in patients with more advanced disease but has not been studied systematically by two-dimensional echocardiography and Doppler color flow mapping in a large referral population with a broader spectrum of severity. In addition, prior reports have suggested that up to 40% of patients with MS have mitral valve prolapse (MVP); however, because of recent developments in two-dimensional echocardiographic imaging and the definition of MVP, this association must now be reconsidered. The purpose of this study was to explore the association of other valvular lesions with MS and their relation to its severity and in particular to test whether MS is in fact associated with MVP with the frequency reported previously. We reviewed the studies of 205 consecutive patients (aged 61 +/- 14 years; range 26 to 87 years) with MS who were studied from 1992 to 1994 by two-dimensional echocardiography and Doppler color flow mapping to assess valvular stenosis, regurgitation, and MVP in patients with a range of severity of MS (28% mild, 34% moderate, and 38% severe MS based on mitral valve area). MS was associated with at least mild mitral regurgitation in 78% of patients (160/205), and pure MS was correspondingly uncommon (22%). There was an inverse relationship between the severity of MS and the degree of mitral regurgitation (p < 0.001). MS was frequently associated (54% of patients) with significant lesions of other valves, including aortic stenosis (17%), at least moderate aortic regurgitation (8%) and tricuspid regurgitation (38%), and tricuspid stenosis (4%). Tricuspid stenosis was associated with more severe MS (p < 0.01), and tricuspid regurgitation was more common in patients with mixed MS and regurgitation than in those with pure stenosis (60% versus 26% for at least moderate tricuspid regurgitation; p < 0.001). Mitral valve prolapse was present in only one patient (0.5%). Superior systolic bulging of the midportion of the anterior mitral leaflet toward the left atrium (but not superior to the annular hinge points) was seen in 22 patients (11%). Patients with such superior bulging had significantly lower mitral valve scores but a similar degree of mitral regurgitation compared with those without bulging. The majority of patients with MS (78%) have associated mitral regurgitation and significant lesions of the other cardiac valves (54%). The frequency of true MVP associated with chronic MS is much lower than reported previously. This may provide insight into the underlying pathophysiologic process, tending to shorten the chordae tendineae and leaflets to produce stenosis rather than elongate them to produce prolapse.
52 citations
TL;DR: It is concluded that the yeast RNA, arginine, and yeast RNA +Arginine diets accelerated ulcer healing, as indicated by decreased ulcer number and length.
Abstract: We previously showed that intravenous totalparenteral nutrition supplemented with nucleosides andnucleotides (NS/NT) promoted ulcer healing in rats withindomethacin-induced ileitis. The present study evaluated whether dietary NT supplementationwould similarly affect ulcer healing in this model.Female Lewis rats were randomized into either control orexperimental groups receiving yeast RNA containing NT or arginine, glutamine, fish oil, guar gum,or a combination of yeast RNA + arginine diets. Ileitiswas induced by two doses of indomethacin (7.5 mg/kg)administered subcutaneously 24 hr apart. Ulcer number and length were determined at 4, 8, and 14 daysafter induction of ileitis. Ileal villous and cryptlength, crypt-villous ratio, and bromodeoxyuridine(BrdU) labeling were studied in the control and yeast RNA-supplemented diet groups. Ileal ulcerationwas present in all groups at 4 and 8 days and was almosthealed by 14 days. Rats receiving yeast RNA, arginine,and yeast RNA + arginine diets showed a significant decrease in ulcer number (56%, 28%, and 34%,respectively) and length (67%, 41%, and 48%,respectively) compared to controls at 8 but not at 4days. Glutamine, fish oil, and guar gum had no effect onulcer healing at 4, 8, or 14 days. Among thehistological parameters, a significant decrease in cryptlength in the yeast RNA-supplemented group at 8 dayssuggested an acceleration of the healing process and restoration to a near-normal crypt-villousarchitecture. We conclude that the yeast RNA, arginine,and yeast RNA + arginine diets accelerated ulcerhealing, as indicated by decreased ulcer number andlength. We postulate that the underlying mechanism(s)contributing to ulcer healing may be related, in part,to increased cell proliferation.
42 citations
TL;DR: AR is a progressive disease not only in patients with severe AR but also in those with mild and moderate regurgitation, and patients with more severe AR have larger left ventricles that also dilate more rapidly.
Abstract: The rate of progression of the degree of chronic aortic regurgitation (AR) is unknown. Furthermore, although left ventricular (LV) dilation has been studied in patients with severe AR, its rate and determining factors, and specifically, its relation to the degree of regurgitation remain to be established and have not previously been studied for mild and moderate AR. The purpose of this study was to explore the progression of chronic AR by 2-dimensional and Doppler echocardiography, and the relation of LV dilation to the fundamental regurgitant lesion and its progression in patients with a full spectrum of initial AR severity. We studied 127 patients with AR by 2-dimensional and Doppler echocardiography (69 men; 59 +/- 21 years; 67 with mild, 45 with moderate, 15 with severe AR). AR increased in 38 patients (30%) (25% of mild, 44% of moderate, and 50% of moderate to severe lesions; p <0.006). The ratio of proximal AR jet height to LV outflow tract height also increased (30.3 +/- 17.5% vs 35.2 +/- 19.7%; p <0.0001). Initial LV volumes and mass were larger in patients with more severe AR and increased significantly during follow-up (138 +/- 53 to 164 +/- 70 ml; 59 +/- 32 to 71.7 +/- 42 ml; 203 +/- 89 to 241 +/- 114 g; p <0.0001). LV volumes and mass increased faster in patients with more severe AR, and in those in whom the degree of AR progressed more rapidly. Finally, patients with bicuspid aortic valve (n = 21) had a higher prevalence of severe AR than patients with tricuspid aortic valves (52% vs 4%; p <0.001). In conclusion, AR is a progressive disease not only in patients with severe AR but also in those with mild and moderate regurgitation. Patients with more severe AR have larger left ventricles that also dilate more rapidly.
42 citations
TL;DR: There is progressive dilation of the aortic root at all levels, even in patients with mild AR, and more rapid progression in aorti root size is associated withMore rapid progression of the underlying aorta insufficiency, as well as more rapid increases in LV volume and mass.
35 citations
TL;DR: A unique force vector cell capable of accurately measuring the three-component force vector applied by the papillary muscle on the left-ventricular wall was designed and manufactured to permit quantification of the alteration in the force balance acting on the mitral leaflets.
14 citations
TL;DR: The prevalence of tricuspid regurgitation remains high at late follow‐up after cardiac transplantation and neither pulmonary hypertension nor right ventricular dilatation are prerequisites for tric Suspid Regurgitation, which can persist in their absence.
Abstract: Tricuspid regurgitation is common immediately after cardiac transplantation, but its course over long-term follow-up is not known. This study was performed to determine the prevalence of valvular regurgitation and to evaluate if pulmonary hypertension or right ventricular enlargement were associated with the severity of tricuspid regurgitation at early and late follow-up after cardiac transplantation. Fifty-five patients had hemodynamic and echocardiographic studies performed at 1 week and 2.4 +/- 1.3 years after cardiac transplantation. Right ventricular dimensions were measured and related to the severity of tricuspid regurgitation as assessed by Doppler color flow. There was a fall in right heart filling pressures with decreases in the systolic pulmonary artery pressure (31 mmHg +/- 7 mmHg vs 27 mmHg +/- 7 mmHg, P = 0.0001) and right atrial pressure (8 +/- 5 mmHg vs 6 +/- 4 mmHg, P < 0.01). Sixty-three percent of patients had mild or higher grade tricuspid regurgitation initially and 71% at follow-up (P = NS). The major determinant of tricuspid regurgitation severity at late follow-up was the presence of flail tricuspid leaflets (P < 0.0001). There was an association between the change in grade of tricuspid regurgitation and the change in right ventricular diastolic area (P = 0.002) and the change in tricuspid annulus diameter (P < 0.0001). The prevalence of tricuspid regurgitation remains high at late follow-up after cardiac transplantation and neither pulmonary hypertension nor right ventricular dilatation are prerequisites for tricuspid regurgitation, which can persist in their absence. Flail tricuspid leaflets are the most important predictors of the severity of tricuspid regurgitation following cardiac transplantation.
8 citations