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Biomedical subjects

M J Garcia

Publications and source records attributed to M J Garcia.

At least 19 recordsLinked to original sources

Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers.

We analysed 148 primary breast cancers using BAC-arrays containing 287 clones representing cancer-related gene/loci to obtain genomic molecular portraits. Gains were detected in 136 tumors (91.9%) and losses in 123 tumors (83.1%). Eight tumors (5.4%) did not have any genomic aberrations in the 281 clones analysed. Common (more than 15% of the samples) gains were observed at 8q11-qtel, 1q21-qtel, 17q11-q12 and 11q13, whereas common losses were observed at 16q12-qtel, 11ptel-p15.5, 1p36-ptel, 17p11.2-p12 and 8ptel-p22. Patients with tumors registering either less than 5% (median value) or less than 11% (third quartile) total copy number changes had a better overall survival (log-rank test: P=0.0417 and P=0.0375, respectively). Unsupervised hierarchical clustering based on copy number changes identified four clusters. Women with tumors from the cluster with amplification of three regions containing known breast oncogenes (11q13, 17q12 and 20q13) had a worse prognosis. The good prognosis group (Nottingham Prognostic Index (NPI) <or=3.4) tumors had frequent loss of 16q24-qtel. Genes significantly associated with estrogen receptor (ER), Grade and NPI were used to build k-nearest neighbor (KNN) classifiers that predicted ER, Grade and NPI status in the test set with an average misclassification rate of 24.7, 25.7 and 35.7%, respectively. These data raise the prospect of generating a molecular taxonomy of breast cancer based on copy number profiling using tumor DNA, which may be more generally applicable than expression microarray analysis.

Breast Neoplasms↗

Ultrasonic characterisation of flour-water systems: a new approach to investigate dough properties.

The viscoelastic properties of dough are of great interest in the baking industry as they affect the quality of the final product. In this work, the viscoelastic properties of dough were investigated using ultrasonic techniques and then compared with traditional methods. It has been shown that ultrasonics provides a non-destructive, rapid and low cost technique for the measurement of physical food characteristics. A common protocol for dough preparation was used for each type of measurement. Experimental results on more than 30 different flour quality and dough processing were presented. The measurements were correlated and compared with traditional dough quality tests. In addition, the capability of ultrasound measurements for discriminating flours for different purposes was also studied, showing the potential of ultrasound as an alternative measurement method to discriminate types of flours for different purposes.

Algorithms↗

Noise level analysis in buffer rod geometries for ultrasonic sensors.

This work presents an ultrasonic sensor for on-line batter monitoring with low-noise design considerations. The density and the compressibility of the batter vary as a function of mixing time and are strongly related to the quality of the final product. Traditionally, a batter sample of a fixed volume is removed and weighted in order to determine its density. This is a time consuming process. Benefits to the industry of on-line measuring techniques include better control of product quality, improving processing efficiencies and reduction in wastage. In this paper low-noise design considerations are accounted for an ultrasonic sensor based on a piezoceramic disk mounted between two reference buffer rods of acrylic resin to measure the acoustic impedance of the batter. Measuring the acoustic impedance changes of the batter its compressibility and density can be monitored. Spurious echoes generated at different parts of the buffer rods boundary strongly affect accuracy and reliability of the measurements, and are considered as noise. The influence of buffer rods geometry on noise level is studied using simulations and afterwards justified experimentally. Design aspects such as buffer rods length and radius, piezoceramic disk frequency and radius are discussed and their influence on noise level is shown. Finally, strategies for optimum geometry design of the ultrasonic sensor are given.

Computer Simulation↗

High-resolution analysis of chromosome rearrangements on 8p in breast, colon and pancreatic cancer reveals a complex pattern of loss, gain and translocation.

The short arm of chromosome 8, 8p, is often rearranged in carcinomas, typically showing distal loss by unbalanced translocation. We analysed 8p rearrangements in 48 breast, pancreatic and colon cancer cell lines by fluorescence in situ hybridization (FISH) and array comparative genomic hybridization, with a tiling path of 0.2 Mb resolution over 8p12 and 1 Mb resolution over chromosome 8. Selected breast lines (MDA-MB-134, MDA-MB-175, MDA-MB-361, T-47D and ZR-75-1) were analysed further. Most cell lines showed loss of 8p distal to a break that was between 31 Mb (5' to NRG1) and the centromere, but the translocations were accompanied by variable amplifications, deletions and inversions proximal to this break. The 8p12 translocation in T-47D was flanked by an inversion of 4 Mb, with a 100 kb deletion at the proximal end. The dicentric t(8;11) in ZR-75-1 carries multiple rearrangements including interstitial deletions, a triplicated translocation junction between NRG1 and a fragment of 11q (unconnected to CCND1), and two separate amplifications, of FGFR1 and CCND1 . We conclude that if there is a tumour suppressor gene on 8p it may be near 31 Mb, for example WRN; but the complexity of 8p rearrangements suggests that they target various genes proximal to 31 Mb including NRG1 and the amplicon centred around ZNF703/FLJ14299.

Breast Neoplasms↗

Hygrothermal degradation of (3-glycidoxypropyl)trimethoxysilane films studied by neutron and X-ray reflectivity and attenuated total reflection infrared spectroscopy.

Thin films of organosilanes have great technological importance in the areas of adhesion promotion, durability, and corrosion resistance. However, it is well-known that water can degrade organosilane films, particularly at elevated temperatures. In this work, X-ray and neutron reflectivity (XR and NR) were combined with attenuated total reflection infrared (ATR-IR) spectroscopy to study the chemical and structural changes within thin films of (3-glycidoxypropyl)trimethoxysilane (GPS) after exposure for various periods of time to air saturated with either D2O or H2O at 80 degrees C. For NR and XR, ultrathin (approximately 100 A) films were prepared by spin-coating. Both D2O and H2O provide neutron scattering contrast with GPS. Variations in the neutron scattering length density (SLD) profiles (a function of mass density and atomic composition) with conditioning time were measured after drying the samples out and also swelled with H2O or D2O vapor at room temperature. For samples that were dried out prior to measurement, little or no change was observed for H2O conditioning up to 3.5 days, but large changes were observed after 30 days of conditioning. The range of conditioning time for this structural change was narrowed to between 4 and 10 days with XR. The SLD profiles indicated that the top portion of the GPS film was transformed into a thick low-density layer after conditioning, but the bottom portion showed little structural change. A previous NR study of as-prepared GPS films involving swelling with deuterated nitrobenzene showed that the central portion of the film has much lower cross-link density than the region nearest the substrate. The present data show that the central portion also swells to a much greater extent with water and hydrolyzes more rapidly. The chemical degradation mechanism was identified by IR as hydrolysis of siloxane bonds. For ATR-IR, GPS films were prepared by dip-coating, which resulted in a greater and more variable thickness than for the spin-coated samples. The IR spectra revealed an increase in vicinal silanol generation over the first 3 days of conditioning followed by geminal silanol generation. Thus, the structural change detected by NR and XR roughly coincided with the onset of geminal silanol generation. Finally, little change in the reflectivity data was observed for films conditioned with D2O at 80 degrees C for 1 month. This indicates that hydrolysis of Si-O-Si is much slower with D2O than with H2O.

Journal Article↗

A dynamic approach to identifying desired physiological phases for cardiac imaging using multislice spiral CT.

In this investigation, we describe a quantitative technique to measure coronary motion, which can be correlated with cardiac image quality using multislice computed tomography (MSCT) scanners. MSCT scanners, with subsecond scanning, thin-slice imaging (sub-millimeter) and volume scanning capabilities have paved the way for new clinical applications like noninvasive cardiac imaging. ECG-gated spiral CT using MSCT scanners has made it possible to scan the entire heart in a single breath-hold. The continuous data acquisition makes it possible for multiple phases to be reconstructed from a cardiac cycle. We measure the position and three-dimensional velocities of well-known landmarks along the proximal, mid, and distal regions of the major coronary arteries [left main (LM), left anterior descending (LAD), right coronary artery (RCA), and left circumflex (LCX)] during the cardiac cycle. A dynamic model (called the "delay algorithm") is described which enables us to capture the same physiological phase or "state" of the anatomy during the cardiac cycle as the instantaneous heart rate varies during the spiral scan. The coronary arteries are reconstructed from data obtained during different physiological cardiac phases and we correlate image quality of different parts of the coronary anatomy with phases at which minimum velocities occur. The motion characteristics varied depending on the artery, with the highest motion being observed for RCA. The phases with the lowest mean velocities provided the best visualization. Though more than one phase of relative minimum velocity was observed for each artery, the most consistent image quality was observed during mid-diastole ("diastasis") of the cardiac cycle and was judged to be superior to other reconstructed phases in 92% of the cases. In the process, we also investigated correlation between cardiac arterial states and other measures of motion, such as the left ventricular volume during a cardiac cycle, which earlier has been demonstrated as an example of how anatomic-specific information can be used in a knowledge-based cardiac CT algorithm. Using these estimates in characterizing cardiac motion also provides realistic simulation models for higher heart rates and also in optimizing volume reconstructions for individual segments of the cardiac anatomy.

Aged↗

Characterization of an rRNA operon (rrnB) of Mycobacterium fortuitum and other mycobacterial species: implications for the classification of mycobacteria.

Mycobacteria are thought to have either one or two rRNA operons per genome. All mycobacteria investigated to date have an operon, designated rrnA, located downstream from the murA gene. We report that Mycobacteriun fortuitum has a second rrn operon, designated rrnB, which is located downstream from the tyrS gene; tyrS is very close to the 3' end of a gene (3-mag) coding for 3-methylpurine-DNA-glycosylase. The second rrn operon of Mycobacterium smegmatis was shown to have a similar organization, namely, 5' 3-mag-tyrS-rrnB 3'. The rrnB operon of M. fortuitum was found to have a single dedicated promoter. During exponential growth in a rich medium, the rrnB and rrnA operons were the major and minor contributors, respectively, to pre-rRNA synthesis. Genomic DNA was isolated from eight other fast-growing mycobacterial species. Samples were investigated by Southern blot analysis using probes for murA, tyrS, and 16S rRNA sequences. The results revealed that both rrnA and rrnB operons were present in each species. The results form the basis for a proposed new scheme for the classification of mycobacteria. The approach, which is phylogenetic in concept, is based on particular properties of the rrn operons of a cell, namely, the number per genome and a feature of 16S rRNA gene sequences.

Base Sequence↗

Different estimates of cardiac power: relationship to altered loading conditions.

Peak instantaneous power is a prognostic index of LV function but is difficult to measure. It is relatively load independent when corrected by preload (EDV2). Easier to acquire power estimates have been proposed--including mean and simplified power. These require only echo Doppler flow and cuff pressures, but their relationship to invasively derived results has not been studied. Using a well-validated numerical model of the cardiovascular system, different estimates of power were compared for varying preload, afterload, and contractility. All power results were divided by EDV2. Estimates of power correlate with peak power over a wide range of physiology. Corrected power estimates were independent of preload and afterload, but predictably increased with contractility. Different estimates of preload corrected power can be derived from non-invasively obtained variables and correlate with corrected peak instantaneous power.

Algorithms↗

Relationship between early diastolic intraventricular pressure gradients, an index of elastic recoil, and improvements in systolic and diastolic function.

BACKGROUND: Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking. METHODS AND RESULTS: Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85). CONCLUSIONS: Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.

Blood Pressure↗

Comparison of new Doppler echocardiographic methods to differentiate constrictive pericardial heart disease and restrictive cardiomyopathy.

This study assesses how the newer modalities of tissue Doppler echocardiography and color M-mode flow propagation compare with respiratory variation of Doppler flow in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. We studied 30 patients referred for further evaluation of diastolic function who had a diagnosis of constrictive pericarditis or restrictive cardiomyopathy established by diagnostic tests, including clinical assessment, magnetic resonance imaging, cardiac catheterization, endomyocardial biopsy, and surgical findings. Nineteen patients had constrictive pericarditis and 11 had restrictive cardiomyopathy. We performed 2-dimensional transesophageal echocardiography combined with pulsed-wave Doppler of the pulmonary veins and mitral inflow with respiratory monitoring, tissue Doppler echocardiography of the lateral mitral annulus, and color M-mode flow propagation of left ventricular filling. Respiratory variation of the mitral inflow peak early (peak E) velocity of > or =10% predicted constrictive pericarditis with 84% sensitivity and 91% specificity and variation in the pulmonary venous peak diastolic (peak D) flow velocity of > or =18% distinguished constriction with 79% sensitivity and 91% specificity. Using tissue Doppler echocardiography, a peak early velocity of longitudinal expansion (peak Ea) of > or =8.0 cm/s differentiated patients with constriction from restriction with 89% sensitivity and 100% specificity. A slope of > or =100 cm/s for the first aliasing contour in color M-mode flow propagation predicted patients with constriction with 74% sensitivity and 91% specificity. Thus, the newer methods of tissue Doppler echocardiography and color M-mode flow propagation are equivalent and complimentary with Doppler respiratory variation in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. The additive role of the new methods needs to be established in difficult cases of constrictive pericarditis where respiratory variation may be absent or decreased.

Adult↗

Occurrence of polycyclic aromatic hydrocarbons in sewage sludge and their contribution to its toxicity in the toxalert 100 bioassay.

The contribution of polycyclic aromatic hydrocarbons (PAH) present in sewage sludge samples to toxicity was investigated. Chemical analysis using gas chromatography mass spectrometry (GC-MS) and the ToxAlert 100 bioassay, based on the inhibition to Vibrio fischeri, were applied to sludge extracts after purification by column chromatography. The levels of the 16 US EPA PAH analyzed in the sewage sludge samples varied from 17 to 2,030 microg kg(-1). In all samples examined phenanthrene was the most prominent compound. The toxicity data obtained by ToxAlert 100 can be explained by the levels and composition of the different PAH in sewage sludge samples. The present approach can contribute to evaluate the toxicity of sewage sludge.

Environmental Monitoring↗

Interaliasing distance of the flow convergence surface for determining mitral regurgitant volume: a validation study in a chronic animal model.

OBJECTIVES: We aimed to validate a new flow convergence (FC) method that eliminated the need to locate the regurgitant orifice and that could be performed semiautomatedly. BACKGROUND: Complex and time-consuming features of previously validated color Doppler methods for determining mitral regurgitant volume (MRV) have prevented their widespread clinical use. METHODS: Thirty-nine different hemodynamic conditions in 12 sheep with surgically created flail leaflets inducing chronic mitral regurgitation were studied with two-dimensional (2D) echocardiography. Color Doppler M-mode images along the centerline of the accelerating flow towards the mitral regurgitation orifice were obtained. The distance between the two first aliasing boundaries (interaliasing distance [IAD]) was measured and the FC radius was mathematically derived according to the continuity equation (R(calc) = IAD/(1 - radicalv(1)/v(2)), v(1) and v(2) being the aliasing velocities). The conventional 2D FC radius was also measured (R(meas)). Mitral regurgitant volume was then calculated according to the FC method using both R(calc) and R(meas). Aortic and mitral electromagnetic (EM) flow probes and meters were balanced against each other to determine the reference standard MRV. RESULTS: Mitral regurgitant volume calculated from R(calc) and R(meas) correlated well with EM-MRV (y = 0.83x + 5.17, r = 0.90 and y = 1.04x + 0.91, r = 0.91, respectively, p < 0.001 for both). However, both methods resulted in slight overestimation of EM-MRV (Delta was 3.3 +/- 2.1 ml for R(calc) and 1.3 +/- 2.3 ml for R(meas)). CONCLUSIONS: Good correlation was observed between MRV derived from R(calc) (IAD method) and EM-MRV, similar to that observed with R(meas) (conventional FC method) and EM-MRV. The R(calc) using the IAD method has an advantage over conventional R(meas) in that it does not require spatial localization of the regurgitant orifice and can be performed semiautomatedly.

Animals↗

Right atrial spontaneous echo contrast and thrombi in atrial fibrillation: a transesophageal echocardiography study.

BACKGROUND: Previous studies have reported the clinical and echocardiographic findings of patients with left atrial spontaneous echo contrast (SEC) and thrombi. We sought to study these characteristics in patients with right atrial SEC and thrombi. METHODS: We reviewed 580 consecutive patients from the ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) Registry and found 79 patients (14%, aged 67 +/-13 years, 67 male) with transesophageal echocardiography (TEE) findings of right atrial SEC or thrombi (group 1). This group was compared with a control group of 75 consecutive patients (group 2) (aged 68 +/- 13 years, P = not significant; 49 male, P <.005) from the registry with no TEE findings of SEC or thrombi in the left or right atrium. RESULTS: Atrial fibrillation was present in 60 of 79 group 1 patients (76%). Five right atrial (6%) and 11 left atrial (14%) thrombi were identified. Both left ventricular ejection fraction (39% +/- 16% versus 47% +/- 14%; P =.0005) and presence of right ventricular dysfunction (n = 44 versus 18; P =.0001) differed significantly between groups 1 and 2, respectively. Right atrial area (24 +/- 6 cm(2) versus 22 +/- 6 cm(2); P = .02) was larger in patients in group 1. Left atrial SEC was present in 68 of 79 group 1 patients (86%). Patients with right atrial thrombi and right atrial SEC had a longer duration of arrhythmia (524 +/-812 days versus 147 +/-368 days, P <.05) than patients with right atrial SEC only. CONCLUSIONS: Right atrial SEC has a prevalence of 14% in patients with atrial arrhythmia who undergo TEE-guided cardioversion. Right atrial thrombi are a rare finding and were seen in fewer than 1% (5/580) of patients with atrial arrhythmia. Right atrial thrombi among patients on anticoagulation therapy were not associated with clinically significant pulmonary embolism.

Adult↗

Comparison of MPEG-1 digital videotape with digitized sVHS videotape for quantitative echocardiographic measurements.

Digital format is rapidly emerging as a preferred method for displaying and retrieving echocardiographic studies. The qualitative diagnostic accuracy of Moving Pictures Experts Group (MPEG-1) compressed digital echocardiographic studies has been previously reported. The goals of the present study were to compare quantitative measurements derived from MPEG-1 recordings with the super-VHS (sVHS) videotape clinical standard. Six reviewers performed blinded measurements from still-frame images selected from 20 echocardiographic studies that were simultaneously acquired in sVHS and MPEG-1 formats. Measurements were obtainable in 1401 (95%) of 1486 MPEG-1 variables compared with 1356 (91%) of 1486 sVHS variables (P <.001). Excellent agreement existed between MPEG-1 and sVHS 2-dimensional linear measurements (r = 0.97; MPEG-1 = 0.95[sVHS] + 1.1 mm; P <.001; Delta = 9% +/- 10%), 2-dimensional area measurements (r = 0.89), color jet areas (r = 0.87, p <.001), and Doppler velocities (r = 0.92, p <.001). Interobserver variability was similar for both sVHS and MPEG-1 readings. Our results indicate that quantitative off-line measurements from MPEG-1 digitized echocardiographic studies are feasible and comparable to those obtained from sVHS.

Echocardiography↗

Respiratory variation of mitral and pulmonary venous Doppler flow velocities in constrictive pericarditis before and after pericardiectomy.

The objective of this study was to determine whether Doppler echocardiography is useful in assessing the effects of pericardiectomy in patients with constrictive pericarditis by studying the postoperative change in the respiratory variation of mitral inflow and pulmonary venous Doppler flows. The study population consisted of 35 cases with surgically proven constrictive pericarditis. Thirty-five patients had preoperative Doppler echocardiography, whereas 4 patients died of non-cardiac causes and 1 patient had a heart transplant before follow-up. Postoperative studies were performed at a mean of 1081 +/- 84 days (range 120-2700 days) after pericardiectomy. The mean (+/- SD) respiratory variation changed after surgery from a baseline value of 17% +/- 14% to 8% +/- 8% for peak mitral E velocity (P <.01); from 25% +/- 18% to 7% +/- 13% (P <.001) for pulmonary venous (PV) peak diastolic flow velocity, and from 21% +/- 13% to 11% +/- 13% (P =.009) for PV peak systolic flow velocity. The 23 patients who became asymptomatic after surgery had a significantly lower mean mitral and PV respiratory variation than the 7 patients who were NYHA class II (4% +/- 4% and 6% +/- 4% vs 21% +/- 6% and 19% +/- 10%, respectively, P <.0001 for both). Pulsed Doppler echocardiographic assessment of respiratory variation is useful for evaluating the outcome of pericardiectomy.

Aged↗

Prediction of coronary artery disease in patients undergoing operations for mitral valve degeneration.

OBJECTIVES: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. METHODS: A total of 722 patients (67% men; age, 61 +/- 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (< or =5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. CONCLUSION: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided.

Algorithms↗