Simultaneous determination of aortic valve area by the Gorlin formula and by transesophageal echocardiography under different transvalvular flow conditions. Evidence that anatomic aortic valve area does not change with variations in flow in aortic stenosis

OBJECTIVES: The purpose of this study was to determine the impact of changes in flow on aortic valve area (AVA) as measured by the Gorlin formula and transesophageal echocardiographic (TEE) planimetry. BACKGROUND: The meaning of flow-related changes in AVA calculations using the Gorlin formula in patients with aortic stenosis remains controversial. It has been suggested that flow dependence of the calculated area could be due to a true widening of the orifice as flow increases or to a disproportionate flow dependence of the formula itself. Alternatively, anatomic AVA can be measured by direct planimetry of the valve orifice with TEE. METHODS: Simultaneous measurement of the planimetered and Gorlin valve area was performed intraoperatively under different hemodynamic conditions in 11 patients. Left ventricular and ascending aortic pressures were measured simultaneously after transventricular and aortic punctures. Changes in flow were induced by dobutamine infusion. Using multiplane TEE, AVA was planimetered at the level of the leaflet tips in the short-axis view. RESULTS: Overall, cardiac output, stroke volume and transvalvular volume flow rate ranged from 2.5 to 7.3 liters/min, from 43 to 86 ml and from 102 to 306 ml/min, respectively. During dobutamine infusion, cardiac-output increased by 42% and mean aortic valve gradient by 54%. When minimal flow was compared with maximal flow, the Gorlin area varied from (mean +/- SD) 0.44 +/- 0.12 to 0.60 +/- 0.14 cm2 (p < 0.005). The mean change in Gorlin area under different flow rates was 36 +/- 32%. Despite these changes, there was no significant change in the planimetered area when minimal flow was compared with maximal flow. The mean difference in planimetered area under different flow rates was 0.002 +/- 0.01 cm2 (p = 0.86). CONCLUSIONS: By simultaneous determination of Gorlin formula and TEE planimetry valve areas, we showed that acute changes in transvalvular volume flow substantially altered valve area calculated by the Gorlin formula but did not result in significant alterations of the anatomic valve area in aortic stenosis. These results suggest that the flow-related variation in the Gorlin AVA is due to a disproportionate flow dependence of the formula itself and not a true change in valve area.     

Application of proximal isovelocity surface area method to determine prosthetic mitral valve area

BACKGROUND: In this study, we investigated the accuracy of orifice area determination of the prosthetic valve (Biocor) by using proximal isovelocity surface area method (PISA). Thirty-two patients (26 women, 6 men; mean age 44 +/- 8.1 years) were studied. Eleven patients were in normal sinus rhythm and the rest were in atrial fibrillation. Associated valvular lesions were mild aortic regurgitation in 12 patients and moderate tricuspid regurgitation in 19 patients. Sizes of prosthetic valves were 27 to 31, and implantation duration was 4 to 8 years. METHODS AND RESULTS: We analyzed the flow convergence zone proximal to the valve orifice with the concept of a hemispheric model. Mitral valve area (MVA) calculation was formulated by MVA = 2pi r2 x Va/Vm x (Vm/Vm-Va), where Vm is the maximal mitral velocity and Vm/Vm - Va is a correction factor to account for flattening of isotachs near the prosthetic orifice. MVA calculations by PISA were compared with pressure half-time (PHT), continuity equation (CONT), and color flow area (CFA) methods. Mitral valve areas were 2.17 +/- 0.17 cm2, 2.22 +/- 0.21 cm2, 2.19 +/- 0.22 cm2, and 2.16 +/- 0.17 cm2 in PISA, CFA, PHT, and CONT methods, respectively. Values in the comparison of MVA measurements by different methods were PISA vs PHT, r =.86; PISA vs CFA, r =.77; and PISA vs CONT, r =.89. CONCLUSIONS: The PISA method gives reliable estimates of large orifices such as prosthetic valves. Although the best correlation was seen with the CONT method, results of this study also confirmed that the PISA method can be applied with reasonable accuracy.     

Effect of bcr-abl oligodeoxynucleotides on the clonogenic growth of chronic myelogenous leukaemia cells

Two-dimensional echocardiographic (2-D) planimetry and the Doppler pressure half-time (PHT) method have been used to estimate mitral valve area (MVA) in patients with mitral stenosis (MS). Recently, the proximal isovelocity surface area (PISA) method has been shown to be accurate for calculating MVA. The purpose of this study was to compare the PISA method with previous methods. Thirty patients with MS were studied; 17 had pure MS, 4 combined mild MR, 6 combined mild AR, and 3 combined MR and AR. Color Doppler flow mapping was performed at an aliasing (blue-red interface) velocity of 14 cm/sec using the zero-baseline shift. MVA was calculated as 2 x 3.14 x R2 x 14 x (theta/180) / PFV, where R is the distance from aliasing to orifice, 14 is the aliasing velocity, theta is the internal angle of the mitral valve, and PFV is the peak flow velocity at the mitral orifice. MVA was also calculated using the 2-D and PHT methods, and compared with the PISA method. MVA calculated using the PISA method correlated well with the 2-D (r=0.90, p < 0.01, SEE = 0.18 cm2) and PHT methods (r=0.82, p < 0.01, SEE = 0.24 cm2). Compared with the 2-D method, the standard error of the estimate of the PISA method was - 0.14+/-0.18 cm2 and the percent error was -10.4+/-18.9%. Compared with the PHT method, the standard error of the estimate of the PISA method was + 0.01+/-0.24 cm2 and the percent error was +3.4+/-34.6%. MVA calculated using the PISA method correlated well with the 2-D and PHT methods in patients with pure MS or with MS combined mild regurgitation. The PISA method may be useful for calculating MVA as an alternative method.     

Acoustic startle, prepulse inhibition, locomotion, and latent inhibition in the neuroleptic-responsive (NR) and neuroleptic-nonresponsive (NNR) lines of mice

To date, studies on the mitral flow convergence method have used rigid, circular, or slit orifices to represent the regurgitant orifice. In this study, explanted porcine mitral valves, with the entire mitral apparatus preserved, were mounted in an in vitro model to reproduce the three-dimensional regurgitant orifice geometry while permitting close control and measurement of the experimental conditions. This experimental setup permitted the evaluation of the hemispheric and hemielliptic formulas under realistic physiologic conditions. In this study, a heart rate of 70 beats/min was used with cardiac outputs between 1.5 and 6 L/min. Peak regurgitant flow rates ranged from 7 to 16 L/min (regurgitant jet velocities ranged from 2 to 5.5 m/sec); peak aortic flow rates ranged from 9 to 30 L/min. Four native mitral valves were used for these studies for a total of 28 stages. Although the hemielliptic modification has previously shown success in vitro and computationally, it has not been used clinically because of difficulty imaging the flow convergence region in three orthogonal planes. A curve-fitting algorithm was developed to extract the hemielliptic dimensions from two standard ultrasound views by rotating the transducer 90 degrees. Improved agreement was obtained between true and calculated flow rates by the hemielliptic formula (y = 1.02 x + 0.29; r = 0.91) compared with the hemispheric formula (y = 1.18 x - 2.2; r = 0.66). This method provides accurate results with a realistic three-dimensional regurgitant orifice geometry and has the capability of being incorporated as a function key on an ultrasound machine for clinical application.     

Doppler haemodynamic assessment of clinically and echocardiographically normal mitral and aortic Allcarbon valve prostheses. Valve Prostheses Ligurian Cooperative Doppler Study

Doppler echocardiographic characteristics of normally functioning Allcarbon prostheses were studied in 149 consecutive patients with 157 valves in the mitral (n = 73) and aortic (n = 84) positions whose function was considered normal by clinical and echocardiographic evaluation. In the mitral position, the mean gradient and the effective mitral orifice area were not significantly different in either the 25-mm or the 31-mm size valves (from 5 +/- 1 to 4 +/- 1 mmHg and from 2.2 +/- 0.6 to 2.8 +/- 0.9 cm2, respectively; P = ns for both). Conversely, peak gradient was significantly and inversely correlated to actual orifice area (r = -0.70; P < 0.0006), decreasing from 15 +/- 3 mmHg in the 25-mm size valve to 9 +/- 1 mmHg in the 31-mm size. In the aortic position, the mean gradient was 29 +/- 8 mmHg in the 19-mm size valve; it decreased to 8 +/- 2 mmHg in the 29-mm size. Effective prosthetic aortic valve area, calculated using the continuity equation, ranged between 0.9 +/- 0.1 cm2 for the 19-mm size valve to 4.1 +/- 0.7 cm2 for the 29-mm size. By analysis of variance, effective prosthetic aortic valve area differentiated various valve sizes (F = 25.3; P < 0.0001) better than peak (F = 5.34; P = 0.012) or mean (F = 4.34; P = 0.0052) gradients alone, and it correlated better with actual orifice area (r = 0.89, r = -0.70 and r = -0.65, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Application of color Doppler flow mapping to calculate orifice area of St Jude mitral valve

BACKGROUND: The effective orifice area (EOA) of a prosthetic valve is superior to transvalvular gradients as a measure of valve function, but measurement of mitral prosthesis EOA has not been reliable. METHODS AND RESULTS: In vitro flow across St Jude valves was calculated by hemispheric proximal isovelocity surface area (PISA) and segment-of-spheroid (SOS) methods. For steady and pulsatile conditions, PISA and SOS flows correlated with true flow, but SOS and not PISA underestimated flow. These principles were then used intraoperatively to calculate cardiac output and EOA of newly implanted St Jude mitral valves in 36 patients. Cardiac output by PISA agreed closely with thermodilution (r=0.91, Delta=-0.05+/-0.55 L/min), but SOS underestimated it (r=0.82, Delta=-1.33+/-0.73 L/min). Doppler EOAs correlated with Gorlin equation estimates (r=0.75 for PISA and r=0.68 for SOS, P<0.001) but were smaller than corresponding in vitro EOA estimates. CONCLUSIONS: Proximal flow convergence methods can calculate forward flow and estimate EOA of St Jude mitral valves, which may improve noninvasive assessment of prosthetic mitral valve obstruction.     

Assessment of mitral regurgitation severity by Doppler color flow mapping of the vena contracta

BACKGROUND: Although Doppler color flow mapping is widely used to assess the severity of mitral regurgitation (MR), a simple, accurate, and quantitative marker of MR by color flow mapping remains elusive. We hypothesized that vena contracta width by color flow mapping would accurately predict the severity of MR. METHODS AND RESULTS: We studied 80 patients with MR. Vena contracta width was measured in multiple views with zoom mode and nonstandard angulation to optimize its visualization. Flow volumes across the left ventricular outflow tract and mitral annulus were calculated by pulsed-Doppler technique to determine regurgitant volume. Effective regurgitant orifice area was calculated by dividing the regurgitant volume by the continuous-wave Doppler velocity-time integral of the MR jet. The cause of MR was ischemia in 24, dilated cardiomyopathy in 34 mitral valve prolapse in 12, endocarditis in 2, rheumatic disease in 2, mitral annular calcification in 1, and uncertain in 5. Regurgitant volumes ranged from 2 to 191 mL. Regurgitant orifice area ranged from 0.01 to 1.47 cm2. Single-plane vena contracta width from the parasternal long-axis view correlated well with regurgitant volume (r = .85, SEE = 20 mL) and regurgitant orifice area (r = .86, SEE = 0.15 cm2). Biplane vena contracta width from apical views correlated well with regurgitant volume (r = .85, SEE = 19 mL) and regurgitant orifice area (r = .88, SEE = 0.14 cm2). A biplane vena contracta width > or = 0.5 cm was always associated with a regurgitant volume > 60 mL and a regurgitant orifice area > 0.4 cm2. A biplane vena contracta width < or = 0.3 cm predicted a regurgitant volume < 60 mL and a regurgitant orifice area < 0.4 cm2 in 24 of 29 patients. No other parameter, including jet area, left atrial size, pulmonary flow reversal, or semiquantitative MR grade, correlated significantly with regurgitant volume or regurgitant orifice area in a multivariate analysis. CONCLUSIONS: Our results demonstrate that careful color flow mapping of the vena contracta of the MR jet provides a simple quantitative assessment of MR that correlates well with quantitative Doppler techniques.     

Normal echocardiographic characteristics of the Sorin Bicarbon bileaflet prosthetic heart valve in the mitral and aortic positions

Doppler echocardiographic characteristics of normally functioning Sorin Bicarbon prostheses were prospectively assessed in 226 consecutive patients (135 male and 91 female patients, mean age 61 +/- 10 years) with 233 valves in the mitral (n = 67) and aortic (n = 166) positions whose function was considered normal by clinical and echocardiographic evaluation. Patterns of "normal" transprosthetic leakage were assessed with transthoracic echocardiography in all valves and with transesophageal echocardiography in six selected mitral valve prostheses. For the mitral valve prostheses, we found that peak and mean gradient, as well as pressure half-time, were not significantly different in either the 25 or the 31 mm valves (median values from 15 to 10 mm Hg, from 4 to 4 mm Hg, and from 70 to 83 ms; p = Not significant for all). On transthoracic study, 12 patients (17%) with a Sorin Bicarbon valve in the mitral position showed minimal transprosthetic leakage. On transesophageal study, all patients showed a transprosthetic leakage whose spatial distribution had a complex pattern: in planes orthogonal to the leaflet axis, two to four jets arising from the hinge points and converging toward the center of the valve plane could be visualized; in planes parallel to the leaflet axis, there were three jets, the two lateral ones diverging and the central one perpendicular to the valve plane. For the aortic valve prostheses, there was a significant decrease in transprosthetic gradients and an increase in effective orifice areas as prosthesis size increased. Peak and mean gradients decreased from a median value of 25 and 13 mm Hg in the 19 mm valves to 9 and 5 mm Hg in the 29 mm valves, respectively. Effective prosthetic valve area calculated with the continuity equation increased from a median value of 0.97 cm2 for the 19 mm size valves to 3.45 cm2 for the 29 mm size. With analysis of variance, effective prosthetic aortic valve area differentiated various valve sizes (F = 40.9, p < 0.0001) better than peak (F = 10.3, p < 0.0001) or mean (F = 8.04, p < 0.0001) gradients alone did. Furthermore, effective prosthetic aortic valve area correlated better than peak and mean gradients with prosthetic size (r = 0.76, r = -0.45, and r = -0.39, respectively). On transthoracic study, 109 patients (66%) showed minimal transprosthetic leakage. These normal values, obtained in a large number of patients with normofunctioning mitral and aortic Sorin Bicarbon valves, may help to identify Sorin Bicarbon prosthesis dysfunction.     

Color Doppler regurgitant jet area for evaluating eccentric mitral regurgitation: an animal study with quantified mitral regurgitation

OBJECTIVES: The purpose of the present study was to rigorously evaluate the accuracy of the color Doppler jet area planimetry method for quantifying chronic mitral regurgitation. BACKGROUND: Although the color Doppler jet area has been widely used clinically for evaluating the severity of mitral regurgitation, there have been no studies comparing the color jet area with a strictly quantifiable reference standard for determining regurgitant volume. METHODS: In six sheep with surgically produced chronic mitral regurgitation, 24 hemodynamically different states were obtained. Maximal color Doppler jet area for each state was obtained with a Vingmed 750. Image data were directly transferred in digital format to a microcomputer. Mitral regurgitation was quantified by the peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions determined using mitral and aortic electromagnetic flow probes. RESULTS: Mean regurgitant volumes varied from 0.19 to 2.4 liters/min (mean [+/- SD] 1.2 +/- 0.59), regurgitant stroke volumes from 1.8 to 29 ml/beat (mean 11 +/- 6.2), peak regurgitant volumes from 1.0 to 8.1 liters/min (mean 3.5 +/- 2.1) and regurgitant fractions from 8.0% to 54% (mean 29 +/- 12%). Twenty-two of 24 jets were eccentric. Simple linear regression analysis between maximal color jet areas and peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions showed correlation, with r = 0.68 (SEE 0.64 cm2), r = 0.63 (SEE 0.67 cm2), r = 0.63 (SEE 0.67 cm2) and r = 0.58 (SEE 0.71 cm2), respectively. Univariate regression comparing regurgitant jet area with cardiac output, stroke volume, systolic left ventricular pressure, pressure gradient, left ventricular/left atrial pressure gradient, left atrial mean pressure, left atrial v wave pressure, systemic vascular resistance and maximal jet velocity showed poor correlation (0.08 < r < 0.53, SEE > 0.76 cm2). CONCLUSIONS: This study demonstrates that color Doppler jet area has limited use for evaluating the severity of mitral regurgitation with eccentric jets.     

Towards a gold standard for quantitative coronary arteriography

Densitometric quantification of coronary artery stenoses in angiographic images can be problematic for two reasons: (i) the x-rays are inadequately oriented with respect to the vessel segments of interest at image acquisition; (ii) non-linear effects due for instance to beam hardening, scattered radiation and veiling glare may reduce the accuracy. As a consequence, appreciable discrepancies between degrees of stenosis measured in two different projections can occur. To overcome these limitations, we have designed and tested a combined correction that compensates (at subsequent analysis) for the error contributions due to the cited sources. It implies 3D reconstruction of the vessel segments of interest and consequently requires an appropriate biplane coronary angiogram. In experiments performed with a dedicated phantom, application of the correction improved the correlation between measured and true area reduction percentages (without correction: y = 1.04x - 4%, r = 0.97, SEE = 6%, n = 35; with correction: y = 1.02x - 0%, r = 0.99, SEE = 3%, n = 35). Applied to ten area stenoses measured biplane in patients and exhibiting strong interplane discrepancies, the correction had a comparable effect (without correction: y = 0.83x - 11%, r = 0.86, SEE = 9%, n = 10; with correction: y = 0.83x + 2%, r = 0.98, SEE = 4%, n = 10). The new densitometric method could possibly be used as a gold standard in the objective evaluation of geometric methods in patients.     

Automated assessment of mitral regurgitant volume and regurgitant fraction by a newly developed digital color Doppler velocity profile integration method

Recent development of the automated cardiac flow measurement (ACFM) method has provided automated measurement of stroke volume and cardiac output by spatial and temporal integration of digital Doppler velocity profile data. The purpose of this study was to evaluate the clinical usefulness of the ACFM method using digital color Doppler velocity profile integration in the assessment of mitral regurgitant volume and regurgitant fraction from measurements of both aortic outflow and mitral inflow volumes. We calculated both aortic outflow and mitral inflow volumes from the apical approach with the ACFM and pulsed Doppler (PD) methods in 20 patients with isolated mitral regurgitation. Mitral regurgitant volume and regurgitant fraction were calculated by the following equation: mitral regurgitant volume = (mitral inflow volume) - (aortic outflow volume), % regurgitant fraction = (mitral regurgitant volume)/(mitral inflow volume) x 100. Mitral regurgitant volume and regurgitant fraction were compared with that determined by the PD method. Mitral regurgitant volume measurement by the ACFM method showed a good correlation with that measured by the PD method (r = 0.90, y = 0.77x + 11.6, SEE = 9.0 ml); the mean differences between PD and ACFM measurements was -1.7 +/- 12.5 ml. Regurgitant fraction estimated by the ACFM method correlated well with that of the PD method (r = 0.92, y = 0.98x + 2.1, SEE = 8.8%). The mean difference for the measurement of regurgitant fraction between the PD and ACFM methods was 0.8 +/- 6.6%. Total time required for mitral regurgitant volume calculation in 1 cardiac cycle by the ACFM method was significantly shorter than that of the PD method (126 +/- 15 seconds vs 228 +/- 36 seconds, p <0.01). In conclusion, the newly developed ACFM method is simple, quick, and accurate in the automated assessment of mitral regurgitant volume and regurgitant fraction.     

Mitral valve area in combined mitral stenosis and regurgitation

Eight patients with mixed mitral stenosis and regurgitation underwent hemodynamic and angiographic study prior to mitral valve replacement. The stenotic orifice of the mitral valve was calculated employing the total left ventricular stroke volume by cineangiography as the numerator of the Gorlin Formula. Excellent agreement with the measured orifice of the mitral valve was obtained using a value of 37.9 (0.85 X 44.5) for the constant in the Gorlin formula as recommended by Cohen and Gorlin. Recalculation of this constant independently by our data yielded a value that was almost identical. Regurgitant flows and orifice sizes were calculated for each patient using the same constant as for calculation of the stenotic orifices.     

3-Hydroxy-3-methylglutaryl coenzyme A lyase: targeting and processing in peroxisomes and mitochondria

Murine models of left ventricular (LV) hypertrophy recently have been developed. We tested the accuracy of 2-dimensional (2D) echocardiographic measurement of LV mass with high-frequency imaging in mice. Ten anesthetized mice (weight 20 to 31 g, aged 1 to 5 months) were examined with a 15-MHz transthoracic linear-array transducer. End-diastolic myocardial area (A)(epicardial - endocardial) from the parasternal short-axis view at the midpapillary level and LV length (L) from the parasternal long-axis view were measured to calculate LV mass with the area-length method (1.05 [5/6 x A x L]) and data were compared with LV-mass with the 2D guided M-mode method. Within 3 days of echocardiography, the hearts were removed and weighed after potassium-induced cardiac arrest. Two-dimensional echocardiographic measurement with a 15-MHz transducer was performed in all mice. LV chamber dimensions included end-diastolic septal (0.80 +/- 0.12 mm) and posterior wall thickness (0.76 +/- 0.13 mm), end-diastolic dimension (3.64 +/- 0.28 mm), and end-systolic dimension (2.34 +/- 0.32 mm). Echocardiographic LV mass with the area-length method, 2D guided M-mode method, and autopsy LV weight were 80.8 +/- 16.1 mg, 97.6 +/- 17.8 mg, and 78.8 +/- 13.2 mg, respectively. A strong correlation existed between LV weight (x ) and echocardiographic LV mass (y ) with the area-length method: y = 0.745x + 18.9, r =0.908, standard error of estimate (SEE) = 5.9 mg, P <.0005. This correlation was stronger than that of LV weight (x ) and echocardiographic LV mass (y ) with the 2D guided M-mode method: y = 0.577x + 22.6, r =0.779, SEE = 8.8 mg, P =.008. These data suggest that serial in vivo measurements of LV mass with the 2D area-length method may be more accurate than M-mode methods in experimental murine models of LV pathology.     

A simplified, practical echocardiographic approach for 3-dimensional surfacing and quantitation of the left ventricle: clinical application in patients with abnormally shaped hearts

The goal of this study was to validate the quantitative accuracy of a system for 3-dimensional (3D) echocardiographic reconstruction of the left ventricle to assess its volume and function in human beings by using 3 apical views as a simplified technique to promote practical clinical application. End-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF) were obtained by 3D echocardiography in 50 patients with dilated or geometrically distorted left ventricles and compared with values from magnetic resonance imaging (20 consecutive patients), angiography (22 consecutive patients), and radionuclide imaging (8 consecutive patients). Three-dimensional results were also compared with 2-dimensional (2D) echocardiographic estimates. Three-dimensional left ventricular reconstruction provided values that correlated and agreed well with pooled data from the other techniques for EDV (y = 0.93x + 9.1, r = 0.95, standard error of the estimate [SEE] = 15.2 mL, mean difference = -0.5 +/- 15.4 mL), ESV (y = 0.94x + 4.3, r = 0. 96, SEE = 11.4 mL, mean difference = 0.4 +/- 11.5 mL), and EF (y = 0. 90x + 4.1, r = 0.92, SEE = 6.2%, mean difference = -0.9 +/- 6.4%) (all mean differences not significant versus 0), with greater errors by 2D echocardiography. Intraobserver and interobserver variabilities of 3D echocardiography were less than 6% for EDV, ESV, and EF. The overall time for image acquisition and 3D reconstruction was 5 to 8 minutes. Although this 3D method uses only a small number of apical views, it accurately calculates EDV, ESV, and EF in patients with dilated and asymmetric left ventricles and is more accurate than 2D echocardiography. The flexible surface fit used to combine the 3 views provides a convenient visual output as well as quantitation. This simple and rapid 3D method has the potential to facilitate routine clinical applications that assess left ventricular function and changes that occur with remodeling.     

Raising the level of medical gerontology: evaluation of the European Academy for Medicine of Ageing course. European Professors of Medical Gerontology

The large-scale solid-phase continuous flow synthesis of the bicyclic peptide MEN 10627, a new potent Neurokinin A receptor antagonist, is described using the Fmoc-polyamide method on both macrosorb 125 and Macrosorb 250 resin. A new synthesizer designed in-house was realized by assembling Whitey valves and Waters pump in order to allow small-scale (0.0001 mol; 1 x 10 cm Omnifit columns) synthetic studies which were strongly predictive of the conditions required for large-scale (0.01-0.10 mol; 3.6 or 5.9 x 46 cm Büchi columns) production, performed on the same apparatus.     

Total body studies in normal British women using dual energy X-ray absorptiometry

We report dual energy X-ray absorptiometry (DXA) studies of total body bone mineral and body composition performed in 111 normal caucasian women (aged 42-61). Conventional DXA scans of the lumbar spine and femoral neck were also obtained and each woman completed a detailed questionnaire. Significant correlations were found between total body BMD and BMD in the lumbar spine (r = 0.76) and femoral neck (r = 0.72). We present reference range data for BMD in the total body and in seven subregions of the skeleton. Multiple linear regressions of total body BMD and BMC on weight, height and age showed that the inclusion of height compared with weight and age alone was not statistically significant. The dependence of total body BMD on weight and age was: total body BMD (g cm-2) = 1.043 + 0.0042 x weight (kg) - 0.0039 x age (years) (R = 0.46, SEE = 0.074 g cm2). Body mass derived from DXA scans correlated well with weight measured on scales (r = 0.996, SEE = 0.77 kg). Body composition measurements agreed closely with % body fat estimated from skinfold measurements (r = 0.93), body fat mass estimated from a predictive equation based on weight, height and age (r = 0.91) and % body fat estimated from a predictive equation based on body mass index (r = 0.76). Study precision gave coefficients of variation of 0.6% for total body BMD and 0.7% for % body fat.     

Reductive cleavage of the disulfide bonds of the collagen IV noncollagenous domain in aqueous sodium dodecyl sulfate: absence of intermolecular nondisulfide cross-links

OBJECTIVES: The goal of this study was to develop an accurate, simplified proximal isovelocity surface area (PISA) method for calculating volume flow rate using lower blue-red interface velocity produced by a color Doppler zero baseline shift technique. BACKGROUND: The Doppler color proximal isovelocity surface area method has been shown to be accurate for calculating the volume flow rate (Q) across a narrowed orifice by the formula Q = PISA x Blue-red interface velocity. A hemispheric model is generally used to calculate proximal isovelocity surface area (PISA = 2 pi a2, where a = the radius corresponding to the blue-red interface velocity). Although a hemispheric model is simple, requiring measurement of one radius, it may underestimate the actual volume flow rate because, in the general case, the shape of a proximal isovelocity surface area is hemielliptic. Although a hemielliptic model is generally more accurate for calculating proximal isovelocity surface area, it is more complex, requiring measurement of two orthogonal radii. METHODS: Sixteen in vitro constant flow model studies were performed using planar circular orifices (diameter range 6 to 16 mm). The blue-red interface velocity was changed from 3 to 54 cm/s using color Doppler zero baseline shift. RESULTS: 1) With decreasing blue-red interface velocity, the size of the proximal isovelocity surface area was increased, and its shape changed from hemielliptic to hemispheric. 2) With the blue-red interface velocity in the range 11 to 15 cm/s, the proximal isovelocity surface area became nearly hemispheric; however, it was difficult to determine the blue-red interface radius at a blue-red interface velocity < 10 cm/s because of interface fluctuations. 3) Calculated volume flow rate using the hemispheric proximal isovelocity surface area model with a single radius was relatively accurate at a blue-red interface velocity of 11 to 15 cm/s (mean percent difference from actual volume flow rate was -3.6%). CONCLUSIONS: Because the shape of the proximal isovelocity surface area is nearly hemispheric at a blue-red interface velocity of 11 to 15 cm/s, volume flow rate can be accurately calculated in this proximal isovelocity surface area interface velocity range (produced by zero baseline shift) by measuring a single-interface radius. This approach should be clinically useful for calculating the volume flow rate across stenotic and regurgitant valves and across shunt defects.     

Comparison of proximal isovelocity surface area method with pressure half-time and planimetry in evaluation of mitral stenosis

OBJECTIVES: This study sought to 1) compare the accuracy of the proximal isovelocity surface area (PISA) and Doppler pressure half-time methods and planimetry for echocardiographic estimation of mitral valve area; 2) evaluate the effect of atrial fibrillation on the accuracy of the PISA method; and 3) assess factors used to correct PISA area estimates for leaflet angulation. BACKGROUND: Despite recognized limitations of traditional echocardiographic methods for estimating mitral valve area, there has been no systematic comparison with the PISA method in a single cohort. METHODS: Area estimates were obtained in patients with mitral stenosis by the Gorlin hydraulic formula, PISA and pressure half-time method in 48 patients and by planimetry in 36. Two different factors were used to correct PISA estimates for leaflet angle (theta): 1) plane-angle factor (theta/180 [theta in degrees]); and 2) solid-angle factor [1-cos(theta/2)]. RESULTS: After exclusion of patients with significant mitral regurgitation, the correlation between Gorlin and PISA areas (0.88) was significantly greater (p < 0.04) than that between Gorlin and pressure half-time (0.78) or Gorlin and planimetry (0.72). The correlation between Gorlin and PISA area estimates was lower in atrial fibrillation than sinus rhythm (0.69 vs. 0.93), but the standard error of the estimate was only slightly greater (0.24 vs. 0.19 cm2). The average ratio of the solid- to the plane-angle correction factors was approximately equal to previously reported values of the orifice contraction coefficient for tapering stenosis. CONCLUSIONS: 1) The accuracy of PISA area estimates in mitral stenosis is at least comparable to those of planimetry and pressure half-time. 2) Reasonable accuracy of the PISA method is possible in irregular rhythms. 3) A simple leaflet angle correction factor, theta/180 (theta in degrees), yields the physical orifice area because it overestimates the vena contracta area by a factor approximately equal to the contraction coefficient for a tapering stenosis.     

Bioelectrical impedance analysis in human immunodeficiency virus-infected patients: comparison of single frequency with multifrequency, spectroscopy, and other novel approaches

Bioelectrical impedance (BIA), a prediction method for estimating body water compartments and body cell mass (BCM), is being increasingly used in studies of human immunodeficiency virus (HIV)-related wasting, but there are few validation studies of the method in this group. The aim of this study is to examine the relationship between impedance measurements and body water compartments in patients with advanced HIV disease, and to investigate whether the newer approaches of multifrequency BIA, BIA spectroscopy, logarithmic transformation using a parallel circuit model, and direct calculation from electrical theory offer any advantage over traditional single-frequency BIA. We measured total body water (TBW) by deuterium dilution and extracellular water by bromide dilution in 33 patients with advanced HIV disease. Intracellular water and BCM were calculated from these results. Impedance was measured over a range of frequencies using a multifrequency analyzer. The relationship between impedance index at various frequencies and body water compartments was assessed by correlation and linear regression. We found that impedance index at higher frequencies had a closer relationship to TBW (r = 0.86, standard error of the estimate [SEE] = 2.96 at 1000 kHz) and at lower frequencies a closer relationship to extracellular water (ECW) (r = 0.47, SEE = 3.13 at 0 kHz) than the traditional 50 kHz measurement (r = 0.84, SE = 3.11 for TBW; r = 0.44 SEE = 3.19 for ECW), but the differences were marginal and not statistically significant. None of the other novel approaches tested were significantly better than traditional single frequency measurement. The 50 kHz equation for BCM developed in this study [BCM (kg) = (0.360331 x Ht2/Z50) + (0.151123 x Wt)-2.95] may be useful to investigators using BIA for hIV-wasting studies.     

Quantification of mitral regurgitation by automated cardiac output measurement: experimental and clinical validation

OBJECTIVES: To develop and validate an automated noninvasive method to quantify mitral regurgitation. BACKGROUND: Automated cardiac output measurement (ACM), which integrates digital color Doppler velocities in space and in time, has been validated for the left ventricular (LV) outflow tract but has not been tested for the LV inflow tract or to assess mitral regurgitation (MR). METHODS: First, to validate ACM against a gold standard (ultrasonic flow meter), 8 dogs were studied at 40 different stages of cardiac output (CO). Second, to compare ACM to the LV outflow (ACMa) and inflow (ACMm) tracts, 50 normal volunteers without MR or aortic regurgitation (44+/-5 years, 31 male) were studied. Third, to compare ACM with the standard pulsed Doppler-two-dimensional echocardiographic (PD-2D) method for quantification of MR, 51 patients (61+/-14 years, 30 male) with MR were studied. RESULTS: In the canine studies, CO by ACM (1.32+/-0.3 liter/min, y) and flow meter (1.35+/-0.3 liter/min, x) showed good correlation (r=0.95, y=0.89x+0.11) and agreement (deltaCO(y-x)=0.03+/-0.08 [mean+/-SD] liter/min). In the normal subjects, CO measured by ACMm agreed with CO by ACMa (r=0.90, p < 0.0001, deltaCO=-0.09+/-0.42 liter/min), PD (r=0.87, p < 0.0001, deltaCO=0.12+/-0.49 liter/min) and 2D (r=0.84, p < 0.0001, deltaCO=-0.16+/-0.48 liter/min). In the patients, mitral regurgitant volume (MRV) by ACMm-ACMa agreed with PD-2D (r= 0.88, y=0.88x+6.6, p < 0.0001, deltaMRV=2.68+/-9.7 ml). CONCLUSIONS: We determined that ACM is a feasible new method for quantifying LV outflow and inflow volume to measure MRV and that ACM automatically performs calculations that are equivalent to more time-consuming Doppler and 2D measurements. Additionally, ACM should improve MR quantification in routine clinical practice.