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Biomedical subjects

M J Garcia

Publications and source records attributed to M J Garcia.

At least 37 records · Page 2Linked to original sources

Mycobacterium immunogenum sp. nov., a novel species related to Mycobacterium abscessus and associated with clinical disease, pseudo-outbreaks and contaminated metalworking fluids: an international cooperative study on mycobacterial taxonomy.

PCR-restriction enzyme pattern analysis of a 439 bp hsp65 gene segment identified 113 unique isolates among non-pigmented rapidly growing mycobacteria (RGM) from clinical and environmental sources that failed to match currently recognized species patterns. This group represented 40% of isolates recovered from bronchoscope contamination pseudo-outbreaks, 0% of disease-associated nosocomial outbreaks and 4% of routine clinical isolates of the Mycobacterium abscessus/Mycobacterium chelonae group submitted to the Mycobacteria/Nocardia laboratory for identification. It is grouped within the Mycobacterium fortuitum complex, with growth in less than 7 d, absence of pigmentation, positive 3-d arylsulfatase reaction and growth on MacConkey agar without crystal violet. It exhibited overlapping biochemical, antimicrobial susceptibility and HPLC characteristics of M. abscessus and M. chelonae. By 16S rRNA gene sequencing, these isolates comprised a homogeneous group with a unique hypervariable region A sequence and differed by 8 and 10 bp, respectively, from M. abscessus and M. chelonae. Surprisingly, this taxon contained two copies of the ribosomal operon, compared with single copies in the two related species. By DNA-DNA hybridization, this new group exhibited <30% homology with recognized RGM species. The name Mycobacterium immunogenum sp. nov. is proposed for this new taxon.

Bacterial Proteins↗

Characterization of a Mycobacterium intracellulare variant strain by molecular techniques.

This paper describes a Mycobacterium intracellulare variant strain causing an unusual infection. Several isolates obtained from an immunocompromised patient were identified as members of the Mycobacterium avium complex (MAC) by the commercial AccuProbe system and biochemical standard identification. Further molecular approaches were undertaken for a more accurate characterization of the bacteria. Up to seven different genomic sequences were analyzed, ranging from conserved mycobacterial genes such as 16S ribosomal DNA to MAC-specific genes such as mig (macrophage-induced gene). The results obtained identify the isolates as a variant of M. intracellulare, an example of the internal variability described for members of the MAC, particularly within that species. The application of other molecular approaches is recommended for more accurate identification of bacteria described as MAC members.

Amino Acid Sequence↗

Estimation of left ventricular operating stiffness from Doppler early filling deceleration time in humans.

Shortened early transmitral deceleration times (E(DT)) have been qualitatively associated with increased filling pressure and reduced survival in patients with cardiac disease and increased left ventricular operating stiffness (K(LV)). An equation relating K(LV) quantitatively to E(DT) has previously been described in a canine model but not in humans. During several varying hemodynamic conditions, we studied 18 patients undergoing open-heart surgery. Transesophageal echocardiographic two-dimensional volumes and Doppler flows were combined with high-fidelity left atrial (LA) and left ventricular (LV) pressures to determine K(LV). From digitized Doppler recordings, E(DT) was measured and compared against changes in LV and LA diastolic volumes and pressures. E(DT) (180 +/- 39 ms) was inversely associated with LV end-diastolic pressures (r = -0.56, P = 0.004) and net atrioventricular stiffness (r = -0.55, P = 0.006) but had its strongest association with K(LV) (r = -0.81, P < 0.001). K(LV) was predicted assuming a nonrestrictive orifice (K(nonrest)) from E(DT) as K(nonrest) = (0.07/E(DT))(2) with K(LV) = 1.01 K(nonrest) - 0.02; r = 0.86, P < 0.001, DeltaK (K(nonrest) - K(LV)) = 0.02 +/- 0.06 mm Hg/ml. In adults with cardiac disease, E(DT) provides an accurate estimate of LV operating stiffness and supports its application as a practical noninvasive index in the evaluation of diastolic function.

Aged↗

Estimation of diastolic intraventricular pressure gradients by Doppler M-mode echocardiography.

Previous studies have shown that small intraventricular pressure gradients (IVPG) are important for efficient filling of the left ventricle (LV) and as a sensitive marker for ischemia. Unfortunately, there has previously been no way of measuring these noninvasively, severely limiting their research and clinical utility. Color Doppler M-mode (CMM) echocardiography provides a spatiotemporal velocity distribution along the inflow tract throughout diastole, which we hypothesized would allow direct estimation of IVPG by using the Euler equation. Digital CMM images, obtained simultaneously with intracardiac pressure waveforms in six dogs, were processed by numerical differentiation for the Euler equation, then integrated to estimate IVPG and the total (left atrial to left ventricular apex) pressure drop. CMM-derived estimates agreed well with invasive measurements (IVPG: y = 0.87x + 0.22, r = 0.96, P < 0.001, standard error of the estimate = 0.35 mmHg). Quantitative processing of CMM data allows accurate estimation of IVPG and tracking of changes induced by beta-adrenergic stimulation. This novel approach provides unique information on LV filling dynamics in an entirely noninvasive way that has previously not been available for assessment of diastolic filling and function.

Animals↗

Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload.

Myocardial tissue Doppler echocardiography (TDE) has been proposed as a tool for the assessment of diastolic function. Controversy exists regarding whether TDE measurements are influenced by preload. In this study, left ventricular volume and high-fidelity pressures were obtained in eight closed-chest dogs during intermittent caval occlusion. The time constant of isovolumic ventricular relaxation (tau) was altered with varying doses of dobutamine and esmolol. Peak early diastolic myocardial (E(m)) and transmitral (E) velocities were measured before and after preload reduction. The relative effects of changes in preload and relaxation were determined for E(m) and compared with their effects on E. The following results were observed: caval occlusion significantly decreased E (DeltaE = 16.4 +/- 3.3 cm/s, 36.6 +/- 13.7%, P < 0.01) and E(m) (DeltaE(m) = 1. 3 +/- 0.4 cm/s, 32.5 +/- 26.1%, P < 0.01) under baseline conditions. However, preload reduction was similar for E under all lusitropic conditions (P = not significant), but these effects on E(m) decreased with worsening relaxation. At tau < 50 ms, changes in E(m) with preload reduction were significantly greater (DeltaE(m) = 2.8 +/- 0.6 cm/s) than at tau = 50-65 ms (DeltaE(m) = 1.2 +/- 0.2 cm/s) and at tau >65 ms (DeltaE(m) = 0.5 +/- 0.1 cm/s, P < 0.05). We concluded that TDE E(m) is preload dependent. However, this effect decreases with worsening relaxation.

Animals↗

Effect of cardiac output on mitral valve area in patients with mitral stenosis: validation and pitfalls of the pressure half-time method.

BACKGROUND AND AIM OF THE STUDY: The non-invasive evaluation of mitral valve area is often used in the assessment of patients with mitral stenosis. The pressure half-time method is commonly used to calculate valve area, but is inaccurate in many clinical scenarios. We sought to quantify the effects of changing cardiac output on the accuracy of mitral valve area determination. METHODS: Thirteen patients with mitral stenosis underwent routine stress echocardiography with resting and peak exercise results compared. A previously described and clinically validated mathematical model of the cardiovascular system was used to validate the clinical results. Seven different loading conditions for each of four different stenotic valve areas were modeled. RESULTS: In patients, with increasing cardiac output, pressure half-time decreased (-30.6+/-35.3 ms/l/min) and calculated valve area increased by 0.25+/-0.30 cm2/l/min. By continuity, it appeared that approximately half of this increase was due to actual valve orifice stretching, the remainder reflecting fundamental changes in the relationship between half-time and valve area. Mathematical modeling resulted in similar changes in pressure half-time and calculated valve area (0.06 to 0.12 cm2/l/min, p = 0.20 versus clinical results). CONCLUSION: Changes in cardiac output result in predictable changes in pressure half-time, and should be considered when performing serial examinations in patients with mitral stenosis.

Adult↗

Automated quantification of mitral valve regurgitation based on normalized centerline velocity distribution.

Previous echocardiographic techniques for quantifying valvular regurgitation are limited by factors including uncertainties for orifice location and a hemispheric convergence assumption that often results in over- and underestimation of flow rate and regurgitant orifice area. Using computational fluid dynamics simulations, these factors were eliminated, allowing a more accurate assessment of regurgitation. A model was developed to allow automated quantification of regurgitant orifice diameter based on the centerline velocity data available from color M-mode echocardiography. The model, validated using in vitro unsteady flow data, demonstrated improved accuracy for orifice diameter (y=0.95x + 0.38, r=0.96) and volume (y=1.18x - 4.72, r=0.93).

Blood Flow Velocity↗

Automated assessment of noninvasive filling pressure using color Doppler M-mode echocardiography.

Assessment of left ventricular filling pressure usually requires invasive hemodynamic monitoring to follow the progression of disease or the response to therapy. Previous investigations have shown accurate estimation of wedge pressure using noninvasive Doppler information obtained from the ratio of the wave propagation slope from color M-mode (CMM) images and the peak early diastolic filling velocity from transmitral Doppler images. This study reports an automated algorithm that derives an estimate of wedge pressure based on the spatiotemporal velocity distribution available from digital CMM Doppler images of LV filling.

Adult↗

Noninvasive assessment of mitral inertness [correction of inertance]: clinical results with numerical model validation.

Inertial forces (Mdv/dt) are a significant component of transmitral flow, but cannot be measured with Doppler echo. We validated a method of estimating Mdv/dt. Ten patients had a dual sensor transmitral (TM) catheter placed during cardiac surgery. Doppler and 2D echo was performed while acquiring LA and LV pressures. Mdv/dt was determined from the Bernoulli equation using Doppler velocities and TM gradients. Results were compared with numerical modeling. TM gradients (range: 1.04-14.24 mmHg) consisted of 74.0 +/- 11.0% inertial forcers (range: 0.6-12.9 mmHg). Multivariate analysis predicted Mdv/dt = -4.171(S/D (RATIO)) + 0.063(LAvolume-max) + 5. Using this equation, a strong relationship was obtained for the clinical dataset (y=0.98x - 0.045, r=0.90) and the results of numerical modeling (y=0.96x - 0.16, r=0.84). TM gradients are mainly inertial and, as validated by modeling, can be estimated with echocardiography.

Aged↗

Relationship between systolic and diastolic function with improvements in forward stroke volume following reduction in mitral regurgitation.

Efforts to improve mitral regurgitation (MR) are often performed in conjunction with coronary revascularization. However, the independent effects of a reduced MR area (MRa) are difficult to quantify. Using a previously developed cardiovascular model, ventricular contractility (elastance 1-8 mmHg/ml) and relaxation (tau: 40-150 msec) were independently adjusted for four grades of MR orifice areas (0.0 to 0.8 cm2). Improvements in forward stroke volume (fSV) were determined for the permutations of reduced MRa. For all conditions, LV end-diastolic pressure and volumes ranged from 7.3-24.2 mmHg and 64.8-174.3 ml, respectively. Overall, fSV ranged from 36.0-89.4 (mean: 64.2 +/- 12.8) ml, improved between 6.4 and 35.3% (mean: 15.6 +/- 8.1%), and was best predicted by (r=0.97, p<0.01) %delta(fSV)[correction of fVS]=34[MRa initial] - 46[MRa final] -0.5[elastance]. Reduced MRa, independent of relaxation and minimally influence by contractility, yield improved fSVs.

Blood Pressure↗

Echocardiographic assessment of the mechanisms of correction of bileaflet prolapse causing mitral regurgitation with only posterior leaflet repair surgery.

Recent data suggest that posterior leaflet repair alone corrects mitral regurgitation in patients with bileaflet prolapse and normal anterior chordae. The purpose of this study was to use echocardiography to define the anatomic differences between posterior and bileaflet prolapse and to determine if posterior leaflet repair alone leads to correction of bileaflet prolapse. We studied patients who underwent quadrangular resection of the posterior mitral valve leaflet to treat bileaflet prolapse (group I, n = 20) or isolated posterior leaflet prolapse (group II, n = 20). Echocardiographic characteristics were compared before and after the procedure. There were no differences in the left ventricular end-diastolic or end-systolic dimensions or function between the 2 groups. However, anterior leaflet length was greater in patients with bileaflet prolapse (3.3 +/- 0.6 cm vs 2.6 +/- 0.4 cm, p = 0.003). In group I, posterior leaflet repair changed anterior leaflet displacement from -0.8 +/- 0.2 to 0.5 +/- 0.4 cm (p <0.001) and posterior leaflet displacement from -0.8 +/- 0.3 cm below to 0.5 +/- 0.4 cm (p <0.001) in front of the mitral annular plane. In group II, anterior leaflet displacement was unchanged from 0.2 +/- 0.1 to 0.3 +/- 0.2 cm (p = 0.22), whereas posterior leaflet displacement changed from -0.7 +/- 0.2 to 0.4 +/- 0.2 cm (p <0.001). Thus, patients with bileaflet prolapse and no ruptured chords have excessive anterior leaflet length. In such patients, posterior leaflet repair alone corrects anterior and posterior leaflet prolapse.

Chi-Square Distribution↗

Noninvasive estimation of transmitral pressure drop across the normal mitral valve in humans: importance of convective and inertial forces during left ventricular filling.

OBJECTIVES: We hypothesized that color M-mode (CMM) images could be used to solve the Euler equation, yielding regional pressure gradients along the scanline, which could then be integrated to yield the unsteady Bernoulli equation and estimate noninvasively both the convective and inertial components of the transmitral pressure difference. BACKGROUND: Pulsed and continuous wave Doppler velocity measurements are routinely used clinically to assess severity of stenotic and regurgitant valves. However, only the convective component of the pressure gradient is measured, thereby neglecting the contribution of inertial forces, which may be significant, particularly for nonstenotic valves. Color M-mode provides a spatiotemporal representation of flow across the mitral valve. METHODS: In eight patients undergoing coronary artery bypass grafting, high-fidelity left atrial and ventricular pressure measurements were obtained synchronously with transmitral CMM digital recordings. The instantaneous diastolic transmitral pressure difference was computed from the M-mode spatiotemporal velocity distribution using the unsteady flow form of the Bernoulli equation and was compared to the catheter measurements. RESULTS: From 56 beats in 16 hemodynamic stages, inclusion of the inertial term ([deltapI]max = 1.78+/-1.30 mm Hg) in the noninvasive pressure difference calculation significantly increased the temporal correlation with catheter-based measurement (r = 0.35+/-0.24 vs. 0.81+/-0.15, p< 0.0001). It also allowed an accurate approximation of the peak pressure difference ([deltapc+I]max = 0.95 [delta(p)cathh]max + 0.24, r = 0.96, p<0.001, error = 0.08+/-0.54 mm Hg). CONCLUSIONS: Inertial forces are significant components of the maximal pressure drop across the normal mitral valve. These can be accurately estimated noninvasively using CMM recordings of transmitral flow, which should improve the understanding of diastolic filling and function of the heart.

Aged↗

Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers.

OBJECTIVES: We sought to determine the relationship between different echocardiographic indices and pulmonary capillary wedge pressures (PCWP) in normal volunteers. BACKGROUND: Indices based on tissue Doppler (TDE) and color M-mode (CMM) echocardiography have been proposed to reflect left (LV) ventricular filling pressures. These include the ratio of early diastolic transmitral velocity (E) to early myocardial velocity measured by TDE (E') and the ratio of E to the wave propagation velocity (Vp) measured from CMM images. These indices, however, have not been validated in normal individuals. METHODS: We studied seven volunteers during two phases of preload altering maneuvers, baseline, with two stages of lower body negative pressure, and repeat baseline with two stages of volume loading. The PCWP obtained from right heart catheterization was compared with diastolic indices using pulsed Doppler, TDE and CMM echocardiography. RESULTS: The PCWP ranged from 2.2 to 23.5 mm Hg. During preload alterations, significant changes in E and septal E' (both p < 0.05) but not lateral E' or Vp were observed. Furthermore, E, septal E' and E/Vp correlated with PCWP (all r > 0.80) but not combined E and TDE indices (both r < 0.15). Within individuals, a similar linear relationship was observed among E/Vp, E and septal E' (average r > 0.80). CONCLUSIONS: In subjects without heart disease, E, septal E' and E/Vp correlate with PCWP. Because the influence of ventricular relaxation is minimized, the ratio E/Vp may be the best overall index of LV filling pressures.

Adult↗

National use of the transesophageal echocardiographic-guided approach to cardioversion for patients in atrial fibrillation.

Transesophageal echocardiographic (TEE)-guided cardioversion of patients in atrial fibrillation (AF) of >2 days' duration is used as an alternative to conventional therapy. The purpose of this study was to investigate practice patterns employed for stroke prophylaxis in patients with AF who underwent cardioversion, and to determine the relative use of conventional and TEE-guided management strategies. We forwarded regionally stratified survey questionnaires to 947 clinical practices within the United States. The 10-question questionnaire queried demographic and clinical practice volumes and practices for managing patients with AF who underwent cardioversion. In addition, we used historical data to determine longitudinal use patterns of the TEE-guided approach for a large institution over 7 years. The 197 completed and returned surveys yielded a return rate of 20.8%. The TEE-guided approach was employed in approximately 12% of total cardioversions, but 75% of practices indicated that they employed transesophageal echocardiography only occasionally. The TEE-guided approach was associated with community size (r = 0.19; p<0.008), type of practice (r = 0.26; p = 0.001), total use of transesophageal echocardiography (r = 0.48; p<0.001), and volume of cardioversions (r = 0.28; p<0.001). Importantly, there was little consensus on the most appropriate clinical indications for TEE-guided cardioversions, and the proportions of TEE-guided cardioversion to total number of electrical cardioversions remained stable over 7 years. Practice volume and physician training may be the most important variables in the adoption of the TEE approach.

Ambulatory Care↗

Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function.

BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.

Adult↗

The echo-Doppler evaluation of left ventricular diastolic function. A current perspective.

The role of left ventricular (LV) diastolic function in health and disease is still incompletely understood and under appreciated by most primary care physicians and many cardiologists. Physical examination, electrocardiogram, and chest radiographs are unreliable in making the diagnosis of LV diastolic dysfunction in most individuals, and invasive measurements of cardiac pressures, rates of LV relaxation, and LV compliance are costly, clinically impracticable as they carry increased risk, and require special catheters and software analysis programs. The authors address the definition of LV diastolic dysfunction, history of diastole, LV filling patterns, pulmonary venous flow velocity variables, additional ancillary data, practical echo-Doppler evaluation of LV diastolic function, and limitations.

Diastole↗

Color M-mode Doppler flow propagation velocity is a preload insensitive index of left ventricular relaxation: animal and human validation.

OBJECTIVES: To determine the effect of preload in color M-mode Doppler flow propagation velocity (v(p)). BACKGROUND: The interpretation of Doppler filling patterns is limited by confounding effects of left ventricular (LV) relaxation and preload. Color M-mode v(p) has been proposed as a new index of LV relaxation. METHODS: We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and v(p) were extracted by digital analysis of color M-mode Doppler images. RESULTS: In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 +/- 21 to 42 +/- 17 cm/s (p < 0.001) without change in v(p) (from 35 +/- 15 to 35 +/- 16, p = 0.99). Results were similar in humans (from 69 +/- 15 to 53 +/- 22 cm/s, p < 0.001, and 37 +/- 12 to 34 +/- 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and v(p) (r = 0.78, p < 0.001, r = 0.86, p < 0.001). CONCLUSIONS: Our results indicate that color M-mode Doppler v(p) is not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.

Aged↗