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Biomedical subjects

E Morris

Publications and source records attributed to E Morris.

At least 19 recordsLinked to original sources

Insights from three-dimensional echocardiographic laser stereolithography. Effect of leaflet funnel geometry on the coefficient of orifice contraction, pressure loss, and the Gorlin formula in mitral stenosis.

BACKGROUND: Three-dimensional echocardiography can allow us to address uniquely three-dimensional scientific questions, for example, the hypothesis that the impact of a stenotic valve depends not only on its limiting orifice area but also on its three-dimensional geometry proximal to the orifice. This can affect the coefficient of orifice contraction (Cc = effective/anatomic area), which is important because for a given flow rate and anatomic area, a lower Cc gives a higher velocity and pressure gradient, and Cc, routinely assumed constant in the Gorlin equation, may vary with valve shape (60% for a flat plate, 100% for a tube). To date, it has not been possible to study this with actual valve shapes in patients. METHODS AND RESULTS: Three-dimensional echocardiography reconstructed valve geometries typical of the spectrum in patients with mitral stenosis: mobile doming, intermediate conical, and relatively flat immobile valves. Each geometry was constructed with orifice areas of 0.5, 1.0 and 1.5 cm2 by stereolithography (computerized laser polymerization) (total, nine valves) and studied at physiological flow rates. Cc varied prominently with shape and was larger for the longer, tapered dome (more gradual flow convergence proximal and distal to the limiting orifice): for an anatomic orifice of 1.5 cm2, Cc increased from 0.73 (flat) to 0.87 (dome), and for an area of 0.5 cm2, from 0.62 to 0.75. For each shape, Cc increased with increasing orifice size relative to the proximal funnel (more tubelike). These variations translated into important differences of up to 40% in pressure gradient for the same anatomic area and flow rate (greatest for the flattest valves), with a corresponding variation in calculated Gorlin area (an effective area) relative to anatomic values. CONCLUSIONS: The coefficient of contraction and the related net pressure loss are importantly affected by the variations in leaflet geometry seen in patients with mitral stenosis. Three-dimensional echocardiography and stereolithography, with the use of actual information from patients, can address such uniquely three-dimensional questions to provide insight into the relations between cardiac structure, pressure, and flows.

Blood Pressure

Transdifferentiation of chicken embryonic cells into muscle cells by the 3' untranslated region of muscle tropomyosin.

Transfection with a plasmid encoding the 3' untranslated region (3' UTR) of skeletal muscle tropomyosin induces chicken embryonic fibroblasts to express skeletal tropomyosin. Such cells become spindle shaped, fuse, and express titin, a marker of striated muscle differentiation. Skeletal muscle tropomyosin and titin organize in sarcomeric arrays. When the tropomyosin 3' UTR is expressed in osteoblasts, less skeletal muscle tropomyosin is expressed, and titin expression is delayed. Some transfected osteoblasts become spindle shaped but do not fuse nor organize these proteins into sarcomeres. Transfected cells expressing muscle tropomyosin organize muscle and nonmuscle isoforms into the same structures. Thus, the skeletal muscle tropomyosin 3' UTR induces transdifferentiation into a striated muscle phenotype in a cell-type-specific context.

Animals

Demonstration of popliteal artery entrapment on leg muscle scintigraphy with 99mTc MIBI and single photon emission tomography.

Popliteal artery entrapment is difficult to diagnose even at surgery. Early diagnosis is important as the prognosis is better if detected before the onset of complications. There is no sensitive method for the evaluation of this condition. We describe three cases detected by a new technique using 99mTc methoxy isobutyl isonitrile (MIBI) with single photon emission tomography. The scintigraphic features of entrapment and the advantage of MIBI leg scintigraphy over other methods are discussed.

Adult

The structure of F-actin. Results of global searches using data from electron microscopy and X-ray crystallography.

The structure of F-actin was investigated by fitting the crystallographically determined actin monomer structure to F-actin electron microscopy data sets obtained by a variety of methods. A reciprocal-space global search procedure was applied to non-equatorial reciprocal-space amplitudes and phases of the microscopy data to locate minima. Fits were performed over a range of cross-sectional radii-of-gyration encompassing values obtained from X-ray solution scattering measurements. Five data sets from four laboratories were investigated: one from frozen-hydrated single filaments, three from negatively stained single filaments, and one from negatively stained single-layer paracrystals. In this last case the paracrystal data were straightened to improve resolution. The best fits nearly unanimously favored a monomer orientation having long-pitch connectivity that was close to that obtained by fitting X-ray fiber diffraction patterns. In certain cases where the resolving power was low, competitive fits were obtained with a quite different orientation, one having only protomer connectivity along the genetic helix. Using a running 10-residue deletion from the monomer in the Holmes-type orientation, subtle differences between the monomer structure and the protomer structure in F-actin could be detected. In particular, differences in the "DNase loop" (residues 41 to 50) and the "hydrophobic loop" (residues 264 to 273) were seen in single-filament data. In addition, a perturbation of the structure was seen in a region near residues 81 to 90. A rearrangement within the protomer structure reported in the literature did not produce fits as good as those obtained when using the undistorted monomer crystallographic structure without 10-residue deletions. These results, taken as a whole, provide strong support for a structure of Mg(2+)-ADP F-actin similar to that originally suggested by Holmes et al. but with alterations of the hydrophobic loop, the DNase loop and in the region near residues 81 to 90. These latter two regions have been proposed as secondary binding sites for myosin heads. The available evidence from electron microscopy and from other sources suggests that residues 40 to 49 are disordered in Mg(2+)-ADP F-actin.

Actins

Combining electron microscopy and X-ray crystallography data to study the structure of F-actin and its implications for thin-filament regulation in muscle.

The convergence of structures, all determined by independent global searches and subsequent refinement on different electron microscopy data sets, with the X-ray fiber diffraction results strongly suggests that we now have the approximately correct structure for F-actin. This consensus structure will now provide a reliable, well-defined platform upon which to study the structure and function of proteins bound to actin. Among these are capping proteins, such as severin and gelsolin, contractile proteins, such as myosin and its subfragments, and proteins involved in regulation, such as troponin and tropomyosin.

Actins

Quantification of tricuspid regurgitation by means of the proximal flow convergence method: a clinical study.

Quantitation of valvular regurgitation remains an important goal in clinical cardiology. It has been described previously that with the use of color Doppler flow mapping, simple measurements of apparent jet size do not correlate closely with quantitative regurgitant indices. 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. Assuming hemispherical convergence, flow rate Q can be calculated as Q = 2 pi r2va, where va is the aliasing velocity at a distance r from the orifice. For maximal accuracy, previously validated correction factors must be used to account for the flattening effect of the isovelocity contours close to the orifice and for the actual sector angle subtended by the valve leaflets (alpha), to yield a flow rate formula Q = 2 pi r2va.(vp/vp - va).(alpha/180), where vp is the orifice velocity obtained by continuous wave Doppler. In 45 patients (35 in sinus rhythm, 10 with atrial fibrillation) with tricuspid regurgitation, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated using the proximal flow convergence method and were compared with values obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (SV) calculated by the proximal flow convergence method correlated very closely with values obtained by the Doppler two-dimensional method with r = 0.95 (y = 0.94x + 0.99) and delta SV = -0.3 +/- 5.2 cm3. Regurgitant flow rates (Q) calculated by both methods showed a similar correlation: r = 0.96 (y = 0.97x + 45) and delta Q = 1.6 +/- 429 cm3/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effective regurgitant orifice area in tricuspid regurgitation: clinical implementation and follow-up study.

Analysis of the flow-convergence zone proximal to a regurgitant orifice permits the noninvasive, quantitative measurement of clinically useful parameters of valvular insufficiency. However, many indexes such as flow rate reflect not only the size of the regurgitant lesion but are also highly dependent on the hemodynamic loading conditions. The effective regurgitant orifice area (ROA) in contrast is a more fundamental parameter, less dependent on hemodynamics and more reflective of real changes in the geometry of the valve, making it a promising index for serial assessment of patients. In this study, the measurement of regurgitant orifice area by the flow-convergence method was tested in tricuspid regurgitation and then used to monitor patients noninvasively over time. The effective ROA was calculated in 45 patients with tricuspid regurgitation by means of the flow-convergence method and compared with the ROA obtained with pulsed Doppler echocardiographic methods. An excellent correlation was obtained between the two assessments of ROA (r = 0.96, delta ROA = -0.09 +/- 6.5 mm2). ROA also showed an excellent correlation with other indexes of valvular insufficiency such as regurgitant stroke volume (r = 0.89) and regurgitant fraction (r = 0.88). In a subgroup of 22 patients thought to be clinically stable, ROA was calculated serially over a mean follow-up period of 2 months and its variability compared with that of other flow-based parameters obtainable from proximal acceleration. The variation between the two studies in regurgitant stroke volume and regurgitant flow rate was 5% +/- 20.6% and 5.2% +/- 35.7%, respectively. The effective ROA showed significantly less variability at 1.8% +/- 15%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[The use of the proximal acceleration method in cases of incompetence of the right atrioventricular valve].

BACKGROUND: Quantitation of valvular regurgitation remains an important goal in cardiology. It has been described previously that using color Doppler flow mapping, measurements of apparent jet size do not correlate always closely with quantitative regurgitant indexes. 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. Assuming hemispherical convergence, peak flow rate Qp can be calculated as Qp = 2 pi r2Va, where Va is the aliasing velocity at a distance r from the orifice. For maximal accuracy, previously validated correction factors must be used to account for the flattening effect of the isovelocity contours close to the orifice and for the actual sector angle subtended by the valve leaflets (alpha) to yield a flow rate formula Qp = 2 pi r2Va (Vp/Vp-Va) (alpha/180), where Vp is the orifice velocity obtained by continuous wave Doppler. METHODS: In 45 patients (35 in sinus rhythm, 10 with atrial fibrillation) with tricuspid regurgitation, regurgitant stroke volume, regurgitant flow rate were calculated using the proximal flow convergence method and compared with values obtained by the Doppler two-dimensional echocardiographic method. RESULTS: Regurgitant stroke volumes (SV) calculated by the proximal flow convergence method correlated very closely with values obtained by the Doppler two-dimensional method with r = 0.95 (y = 0.94x + 0.99) and delta SV = -0.3 +/- 5.2 cm3. Regurgitant flow rates (Q) calculated by both methods showed a similar correlation: r = 0.96 (y = 0.97x + 45) and delta Q = 1.6 +/- 4.29 cm3/min. All correlations were slightly better for the group of patients in sinus rhythm. CONCLUSION: This study demonstrates that the proximal flow convergence method is an accurate and reproducible technique for quantifying tricuspid regurgitation. While improvements of this method are to be expected, flow calculations based on the proximal flow field show excellent results and appear appropriate for clinical use.

Adult

[A description of a new method of quantifying the regurgitant flow in patients with an incompetent mitral valve].

BACKGROUND: It has been shown previously that using color Doppler flow mapping, 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 r2va where va is the aliasing velocity at a distance r from the orifice. PATIENTS AND METHODS: In 54 patients (43 in sinus rhythm, 11 with atrial fibrillation) with at least mild mitral regurgitation by semi-quantitative assessment, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated using the proximal flow convergence method and compared with values obtained by the Doppler/two-dimensional echocardiographic method. RESULTS: Regurgitant stroke volumes (VL) calculated by the proximal flow convergence method correlated very closely with values obtained by the Doppler-2D method with r = 0.93 (y = 0.95x + 0.55) and delta VL = -0.3 +/- 4.0 cm3. Regurgitant flow rates (Q) 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) 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 in sinus rhythm compared with the study group in atrial fibrillation. CONCLUSION: This study demonstrates that the proximal flow convergence method is an accurate and reproducible technique to quantify mitral regurgitation. This approach is easy and less time-consuming than the Doppler-echocardiographic method. While future improvements of this method are to be expected, flow calculations based on the assumption of simple hemispheric symmetry of the proximal flow field appear suitable for clinical application at the present time.

Adult

Which physical factors determine tricuspid regurgitation jet area in the clinical setting?

The visual assessment of jet area has become the most common method used in daily clinic practice to evaluate valvular regurgitation. Despite the high prevalence of tricuspid regurgitation, however, few studies have systematically compared TR jet areas with a quantitative standard. To evaluate this, 40 patients in sinus rhythm with tricuspid regurgitation were analyzed: 16 with centrally directed free jets and 24 with impinging wall jets. The size of the maximal planimetered color jet area (cm2) was compared with parameters derived using the pulsed Doppler 2-dimensional echocardiographic method: regurgitant fraction and the flow convergence method (peak flow rate, effective regurgitant orifice area and momentum). Mean tricuspid regurgitant fraction averaged 33 +/- 15%, peak flow rate 76 +/- 54 cm3/s, effective regurgitant orifice area 27 +/- 21 mm2 and momentum 21,717 +/- 15,014 cm4/s2. An average of 4-chamber, and long- and short-axis areas in free jets correlated well with regurgitant fraction (r = 0.81, p < 0.001), better with peak flow rate (r = 0.94, p < 0.001), effective regurgitant orifice (r = 0.92, p < 0.001) and momentum (r = 0.94, p < 0.001). The correlation was worse, but still significant, in wall jets. For the same peak flow rate, wall jets were 75% of the size of a corresponding free jet. Jet area measurement is a good semiquantitative tool to measure tricuspid regurgitation in free jets, which correlates well with regurgitant fraction and better with new parameters available from analysis of the proximal acceleration field. In patients with eccentrically directed wall jets the correlation with planimetered jet area was worse, but still significant.

Adult

Vimentin mRNA location changes during muscle development.

The mRNAs for some cytoskeletal proteins are localized, suggesting that mRNA for these proteins may concentrate at sites appropriate for assembly. To test this hypothesis, we observed vimentin mRNA in developing chicken muscle cultures by in situ hybridization with a digoxigenin-labeled DNA probe to vimentin, detected by confocal microscopy using fluorescent anti-digoxigenin antibody. This method has submicrometer resolution. In developing muscle, vimentin mRNA was bipolar in young myoblasts, somewhat perinuclear in elongated myoblasts and spread fibroblasts, and diffuse in young and developing myotubes. In mature myotubes, vimentin mRNA occurred at costameres with vimentin protein. Localization of mRNA may prove important for assembling and maintaining differentiated cytoskeletal structures, as it is for organizing the embryo.

Animals

Risk factors for asthma in inner city children.

Inner city children have the highest prevalence and the highest mortality rates for asthma in the United States. The purpose of this study was to evaluate sensitization and exposure to common indoor allergens among children aged 3 years to 15 years seen for treatment of asthma at Grady Memorial Hospital, Atlanta, Ga. Eighty children in this study were enrolled in the emergency department and 64 in hospital clinics. Dust from 57 homes, assayed for three indoor allergens (dust mite, cat, and cockroach), revealed similar exposure for asthma and control groups. Sixty-nine percent of the children with asthma had IgE antibodies to dust mite, cockroach, or cat; only 27% of the control subjects were similarly sensitized (p < 0.001). Of 35 children with asthma 21 had both sensitization and significant exposure to the relevant allergen; this was true for only 3 of 22 control subjects (odds ratio, 9.5; p < 0.001). Neither sensitization nor exposure to cat allergen was common in this population. The results show that black children in inner city Atlanta are exposed to high levels of mite and cockroach allergens and that a high proportion of the children with asthma are sensitized to these allergens; the combination of sensitization and exposure is a major risk factor for asthma in this population.

Adolescent

Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration.

The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.

Adolescent