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PubMed2005

MRI in guiding and assessing intramyocardial therapy.

Cardiovascular intervention, using MRI guidance, is challenging for clinical applications. Real-time imaging sequences with high spatial resolution are needed for monitoring intramyocardial delivery of drug, gene, or stem cell therapies. New generation MR scanners make local intramyocardial and vascular wall therapies feasible. Contrast-enhanced MRI is used for assessing myocardial ischemia, infarction, and scar tissue. Active (microcoils) and passive (T1 and T2* mechanisms) tracking methods have been used for visualization of endovascular catheters. Safety issues related to potential heating of endovascular devices is still a major obstacle for MRI-guided interventions. Fabrication of MRI-compatible interventional devices is limited. Noninvasive imaging strategies will be critical in defining spatial and temporal characteristics of angiogenesis and myocardial repair as well as in assessing the efficacy of new therapies in ischemic heart disease. MRI contrast media improve the capability of MRI by delineating the target and vascular tree. Labeling stem cells enables MRI to trace distribution, differentiation, and survival in myocardium and vascular wall. In the long term, MRI in guiding and assessing intramyocardial therapy may circumvent the limitations of peripherally administered cell therapy, X-ray angiography, and nuclear imaging. MRI represents a highly attractive discipline whose systematic development will foster the implementation of new cardiac and vascular therapies.

Cardiomyopathies↗

PubMed2003

Clinical usefulness of carotid arterial wave intensity in assessing left ventricular systolic and early diastolic performance.

Wave intensity (WI) is a novel hemodynamic index, which is defined as (d P/d t) x (d U/d t) at any site of the circulation, where d P/d t and d U/d t are the derivatives of blood pressure and velocity with respect to time, respectively. However, the pathophysiological meanings of this index have not been fully elucidated in the clinical setting. Accordingly, we investigated this issue in 64 patients who underwent invasive evaluation of left ventricular (LV) function. WI was obtained at the right carotid artery using a color Doppler system for blood velocity measurement combined with an echo-tracking method for detecting vessel diameter changes. The vessel diameter changes were automatically converted to pressure waveforms by calibrating its peak and minimum values by systolic and diastolic brachial blood pressures. The WI of the patients showed two sharp positive peaks. The first peak was found at the very early phase of LV ejection, while the second peak was observed near end-ejection. The magnitude of the first peak of WI significantly correlated with the maximum rate of LV pressure rise (LV max. d P/d t) (r = 0.74, P << 0.001). The amplitude of the second peak of WI significantly correlated with the time constant of LV relaxation (r = -0.77, P << 0.001). The amplitude of the second peak was significantly greater in patients with the inertia force of late systolic aortic flow than in those without the inertia force (3,080 +/- 1,741 vs 1,890 +/- 1,291 mmHg m s(-3), P << 0.01). These findings demonstrate that the magnitude of the first peak of WI reflects LV contractile performance, and the amplitude of the second peak of WI is determined by LV behavior during the period from late systole to isovolumic relaxation. WI is a noninvasively obtained, clinically useful parameter for the evaluation of LV systolic and early diastolic performance at the same time.

Adult↗

PubMed2005

Mechanical frequency and stimulation-site-related differences in vibrotactile detection capacity along the lip vermilion in young adults.

Accurate clinical assessment of the infraorbital and mental branch of the trigeminal nerve is aided by an appreciation of the variations in sensitivity that may exist along the surface of the perioral region under examination. The purpose of this investigation was to map the mediolateral spatial and frequency variations in vibrotactile detection capacity to inputs delivered to the upper lip (UL) and lower lip (LL) vermilion. Mechanical vibrotactile inputs at frequencies of 5, 10, 50, and 150 Hz were delivered to three locations on the vermilion of the UL and LL: midsagittally and laterally (left and right) at a point halfway between the midsagittal plane and the oral angle. An adapted staircase tracking method was used to converge upon a threshold value for each test frequency at each stimulation site. The results indicated that midsagittal vermilion sites were significantly more sensitive to our range of vibrotactile inputs compared to lateral vermilion locations. In addition, no significant differences in sensitivity as a function of laterality or between the UL and LL vermilion sites were noted. Greater midline sensitivity to vibrotactile stimulation suggests that receptive fields at this location may be of greater density and/or demonstrate greater overlap compared to lateral vermilion sites.

Adult↗

PubMed2006

Two-dimensional dynamic simulation of platelet activation during mechanical heart valve closure.

A major drawback in the operation of mechanical heart valve prostheses is thrombus formation in the near valve region. Detailed flow analysis in this region during the valve closure phase is of interest in understanding the relationship between shear stress and platelet activation. A fixed-grid Cartesian mesh flow solver is used to simulate the blood flow through a bi-leaflet mechanical valve employing a two-dimensional geometry of the leaflet with a pivot point representing the hinge region. A local mesh refinement algorithm allows efficient and fast flow computations with mesh adaptation based on the gradients of the flow field in the leaflet-housing gap at the instant of valve closure. Leaflet motion is calculated dynamically based on the fluid forces acting on it employing a fluid-structure interaction algorithm. Platelets are modeled and tracked as point particles by a Lagrangian particle tracking method which incorporates the hemodynamic forces on the particles. A platelet activation model is included to predict regions which are prone to platelet activation. Closure time of the leaflet is validated against experimental studies. Results show that the orientation of the jet flow through the gap between the housing and the leaflet causes the boundary layer from the valve housing to be drawn in by the shear layer separating from the leaflet. The interaction between the separating shear layers is seen to cause a region of intensely rotating flow with high shear stress and high residence time of particles leading to high likelihood of platelet activation in that region.

Algorithms↗

PubMed1990

Genetic studies of variation in Rayleigh and photometric matches in normal trichromats.

The inheritance of Rayleigh match midpoints and photometric matches (551-667 nm) was studied in observers with normal color vision. An analysis was performed to evaluate whether the measured interobserver variations in these two traits were consistent with single gene allelic variation, polygenic variation, or environmental factors. A bipartite 2 deg field and a computerized tracking method were used to obtain Rayleigh matches; a new photometric technique, termed heterochromatic modulation photometry (HMP), was used to obtain photometric matches. Data were collected from 72 nonrelated males to determine distribution characteristics for the normal population. The distributions were analyzed for evidence of multimodality and the results indicated that the distributions for Rayleigh match midpoints and HMP matches obtained in this study were unimodal and symmetrical. Data from 52 observers from 5 families were used to study the transmission of the two traits in pedigrees. Statistical analysis of the pedigree data suggested that the major source of variations for Rayleigh match midpoints and for HMP matches were each due to allelic variation at single gene loci; that is, each may be determined by a single gene. Results were inconclusive as to whether variation in the two traits could be determined by the same gene.

Adolescent↗

PubMed1987

The effects of ethanol on eye tracking in rhesus monkeys and humans.

The effects of ethanol on eye tracking function were compared in rhesus monkeys and humans using a similar experimental procedure. In Experiment 1, 3 rhesus monkeys were trained to visually track a projected image of a disk that oscillated sinusoidally along a horizontal plane on a screen. This training was accomplished using a procedure in which responses on a lever resulted in the delivery of water when the central area of the projected disk image was dimmed for a brief period. Intragastric administrations of ethanol at doses of 0.25 to 2 g/kg were tested during one-day test sessions using a cumulative dose procedure. Pursuit eye movements were disrupted at doses of 0.5 g/kg while lever pressing behavior was not disrupted until a dose of 2 g/kg was reached. In Experiment 2, pursuit eye movements of 6 humans were not disrupted when ethanol was given orally at cumulative doses of 0.25 to 1 g/kg, while microswitch pressing behavior was disrupted in some of the subjects at a dose of 0.5 g/kg. Blood ethanol levels increased in a dose-dependent manner in both species with higher levels in humans than in monkeys. The dose dependent effects observed in both species and qualitative similarities in some of the effects such as saccadic pursuit eye movements suggest that the eye tracking method employing monkeys is useful for predicting drug effects on sensory motor function in humans.

Adult↗

PubMed1984

Binaural masking-level difference as a function of masker and test-signal duration.

The binaural masking-level difference (BMLD) is measured as a function of duration of the masker (uniform masking noise) and of the test tone (400 and 800 Hz). Four observers used a Békésy tracking method which proved to be a time-saving procedure for BMLD measurements. Although the masked threshold depends on the test-tone duration, the BMLD does not. The latter, however, increases from about 5 to 10 dB as the masker duration increases from 10 to 200 ms.

Auditory Threshold↗

PubMed2005

Understanding the mechanisms creating false positive lumpectomy margins.

OBJECTIVE: All breast surgeons deal with the frustration of initial pathologic close or positive margins that have no residual cancer upon re-excision. To understand the mechanisms that create false positive margins, specimen handling was standardized in a single surgeon's practice and margin issues were tracked. METHODS: Prospectively over a 3.5-year period, needle-localized lumpectomies for the management of early-stage breast cancer were standardized in all aspects of specimen handling, including surgeon inking and specimen compression for specimen radiography for quality assurance. The current study reviews 220 such cases where the original lumpectomy included a small piece of overlying skin from over the target lesion. All specimen radiography was performed with compression at the skin to deep level to bias the "pancaking" effect of pushing tumor to specimen surface to the deep margin. RESULTS: Of the 220 therapeutic lumpectomies performed for clinical stage 0-2 breast cancer in this fashion, 175 (79.5%) had negative margins by a distance of 10 mm or more. Margins less than 10 mm were classified as close and were present in 20 (9.1%) of cases. These were heavily biased toward margins closer than 2 mm. Positive initial margins accounted for 25 (11.4%) of cases. Of the 45 close or positive margin cases, 12 involved the deep margin only, and on re-excision none was found to have residual tumor. When other single margins were involved, re-excision found tumor in 5 of 14 cases (35.7%). When multiple margins were close or positive, 9 of 19 cases (47.3%) were found to have residual tumor at re-excision. CONCLUSIONS: Specimen compression increases the incidence of false margin positivity. The best predictors of true margin positivity are multiple close or positive margins or margin positivity in a direction not associated with specimen ex vivo compression.

Breast Neoplasms↗

PubMed2006

Quantum-dot based nanoparticles for targeted silencing of HER2/neu gene via RNA interference.

Gene silencing using short interfering RNA (siRNA) is fast becoming an attractive approach to probe gene function in mammalian cells. Although there have been some success in the delivery of siRNA using various methods, tracking their delivery and monitoring their transfection efficiency prove to be hard without a suitable tracking agent. Therefore, a challenge lies with the design of an efficient and at the same time, self-tracking, transfection agent for RNA interference. In this paper, chitosan nanoparticles (NPs) with encapsulated quantum dots (QDs) were synthesized and used to deliver HER2/neu siRNA. Using such a construct, the delivery and transfection of the siRNA can be monitored by the presence of fluorescent QDs in the chitosan NPs. Targeted delivery of HER2 siRNA to HER2-overexpressing SKBR3 breast cancer cells was shown to be specific with chitosan/QD NP surface labeled with HER2 antibody targeting the HER2 receptors on SKBR3 cells. Gene-silencing effects of the conjugated siRNA was also established using the luciferase and HER2 ELISA assays. These self-tracking siRNA delivery NPs will also aid in the monitoring of future gene silencing studies in vivo.

Biocompatible Materials↗

PubMed2005

Effects of nicotine on hippocampal and cingulate activity during smooth pursuit eye movement in schizophrenia.

BACKGROUND: Abnormal smooth pursuit eye movement (SPEM) in schizophrenic patients is a well known phenomenon, but the neurophysiological mechanisms underlying the deficit are unknown. Nicotine temporarily improves SPEM and has been associated with reduced hippocampal hemodynamic activity in schizophrenics. Nicotine's effect on brain activity in control subjects performing SPEM has not been studied. The purpose of this work was to determine if nicotine differentially affects brain activity in schizophrenic and control subjects during pursuit eye tracking. METHODS: 16 subjects with schizophrenia and 16 control subjects underwent functional MR imaging during SPEM after receiving placebo or nicotine gum. Four brain regions were analyzed for main effects of group, drug, and interactions: hippocampus, cingulate gyrus, frontal eye fields, and area MT. RESULTS: Nicotine reduced hippocampal activity in both groups, but the effect was greater in control subjects. A group by drug interaction was observed in the anterior cingulate gyrus, where nicotine decreased activity in control subjects and increased activity in schizophrenic subjects. There were no significant effects of group, drug, or interactions in frontal eye fields or area MT. CONCLUSIONS: Nicotine may improve SPEM performance in people with schizophrenia through cholinergic stimulation of the hippocampus and cingulate gyrus. Potential mechanisms include improved inhibitory function and attention.

Administration, Oral↗

PubMed2005

Visual evoked potentials discrimination based on adaptive zero-tracking neural network.

A non-linear classifier is proposed to discriminate visual evoked potentials (VEP). It combines two techniques: the zero-tracking method and a multi-layer network. The first method consists of processing the VEP data through an adaptive linear prediction filter aiming at extracting the appropriate feature vector to be fed into the neural network. 105 VEPs collected from 48 healthy people and 57 patients are analysed to test the performances of the proposed classifier. The results obtained with a back-propagation network revealed a total success rate equal to 89%. It is also found more accurate than the latency method used in hospitals.

Algorithms↗

PubMed2006

Uranium levels in the diet of São Paulo City residents.

Natural levels of uranium in the diet of São Paulo City residents were studied, and radionuclide concentrations were measured by the fission track method on samples of typical adult food items. This information was used to evaluate the daily intake of uranium in individuals living in São Paulo City which is, according to our findings, around 0.97 microg U/day. Using the ICRP Uranium-model, we estimated the uranium accumulation and committed doses in some tissues and organs, as function of time. We compared the output of the ICRP uranium biokinetic model, tailored for the conditions prevailing in São Paulo, with experimental data from other localities. Such comparison was possible by means of a simple method we developed, which allows normalization among experimental results from different regions where distinct values of chronic daily intake are observed.

Adult↗

PubMed2006

Linkage Group Selection--a fast approach to the genetic analysis of malaria parasites.

Genetic analysis of malaria parasites has shown that the mechanisms of inheritance in these organisms are classically Mendelian. In other words, alleles of genes at different loci recombine, and alleles at the same gene locus segregate, in the progeny of a genetic cross between two genetically distinct lines of malaria parasite. Importantly, such progeny are haploid in the first filial generation following genetic crossing. Consequently, genetic analysis, including linkage analysis, can be done directly upon the cloned cross progeny. Linkage analysis conducted upon the progeny of genetic crosses between malaria parasites can lead to the location of a single gene controlling a specific phenotype, as has been achieved to identify the gene for chloroquine resistance in Plasmodium falciparum. The work involved, however, is extremely labour intensive. It involves the generation of many hundreds, to a thousand or so, of independent recombinant clones from the cross progeny and the biological characterisation, and genetic typing for hundreds of molecular genetic markers of each such clone. We discuss here a fast-track method for identifying genes controlling specific phenotypes, e.g. drug resistance/sensitivity. It involves the mass screening with quantitative molecular genetic markers of the uncloned progeny of a genetic cross following its growth under a selection pressure representing the phenotype of interest. We have called the method Linkage Group Selection.

Animals↗

PubMed2006

Eye movements and prospective memory: what the eyes can tell us about prospective memory.

In this study we used eye tracking methodology in combination with multi-element displays to examine the processes underlying event-based prospective memory in a visual search paradigm. In the task individuals searched for a different target stimulus (i.e., a letter) on each trial that could be present or absent, and made prospective responses to the letters D or M. The response accuracy data revealed that target hits were more frequent than prospective hits, and that there was no difference in response time for target and prospective responses. The eye tracking data revealed that both first and total fixation durations increased from distractors (stimuli that were neither targets nor prospective cues) to targets to prospective cues when a target or prospective response was made. These measures also revealed that the presence of a target in the display served to disrupt prospective memory. In addition, prospective memory misses resulted from a combination of failures to fixate the prospective cues and failures to engage in strategic processing of the prospective cues. These data demonstrate the utility of eye tracking methods in examining the processes underlying event-based prospective memory.

Analysis of Variance↗

PubMed2006

Impact of a school-based dating violence prevention program among Latino teens: randomized controlled effectiveness trial.

PURPOSE: Given the high rate of dating violence between teens and associated deleterious outcomes, the need for effective prevention and early intervention programs is clear. Break the Cycle's Ending Violence curriculum, a three-class-session prevention program focused on legal issues, is evaluated here for its impact on Latino/a youth. METHODS: Tracks within large urban high schools that had at least 80% Latino/a students were randomized to immediate or delayed curriculum. Classrooms were randomly selected within tracks and individual student outcomes were assessed pre- and postintervention and six months later. RESULTS: Students in intervention classrooms showed improved knowledge, less acceptance of female-on-male aggression, and enhanced perception of the helpfulness and likelihood of seeking assistance from a number of sources immediately after the program. Improved knowledge and perceived helpfulness of an attorney were maintained six months later. There were no differences in recent abusive/fearful dating experiences or violence victimization or perpetration. CONCLUSIONS: The Ending Violence curriculum has an impact on teen norms, knowledge, and help-seeking proclivities that may aid in early intervention for dating violence among Latino/a students.

Adolescent↗

PubMed2006

Microbial source tracking by DNA sequence analysis of the Escherichia coli malate dehydrogenase gene.

Criteria for sub-typing of microbial organisms by DNA sequencing proposed by Olive and Bean were applied to several genes in Escherichia coli to identify targets for the development of microbial source tracking assays. Based on the aforementioned criteria, the icd (isocitrate dehydrogenase), and putP (proline permease) genes were excluded as potential targets due to their high rates of horizontal gene transfer; the rrs (16S rRNA) gene was excluded as a target due to the presence of multiple gene copies, with different sequences in a single genome. Based on the above criteria, the mdh (malate dehydrogenase) gene was selected as a target for development of a microbial source tracking assay. The mdh assay was optimized to analyze a 150 bp fragment corresponding to residues G191 to R240 (helices H10 and H11) of the Mdh catalytic domain. 295 fecal isolates (52 horse, 50 deer, 72 dog, 52 seagull and 69 human isolates) were sequenced and analyzed. Target DNA sequences for isolates from horse, dog plus deer, and seagull formed identifiable groupings. Sequences from human isolates, aside from a low level (ca. 15%) human specific sequence, did not group; nevertheless, other hosts could be distinguished from human. Positive and negative predictive values for two- and three-way host comparisons ranged from 60% to 90% depending on the focus host. False positive rates were below 10%. Multiple E. coli isolates from individual fecal samples exhibited high levels of sequence homogeneity, i.e. typically only one to two mdh sequences were observed per up to five E. coli isolates from a single fecal sample. Among all isolates sequenced from fecal samples from each host, sequence homogeneity decreased in the following order: horse>dog>deer>human and gull. For in-library isolates, blind analysis of fecal isolates (n=12) from four hosts known to contain host specific target sequences was 100% accurate and 100% reproducible for both DNA sequence and host identification. For blind analysis of non-library isolates, 18/19 isolates (94.7%) matched one or more library sequences for the corresponding host. Ten of eleven geographical outlier fecal isolates from Florida had mdh sequences that were identical to in-library sequences for the corresponding host from California. The mdh assay was successfully applied to environmental isolates from an underground telephone vault in California, with 4 of 5 isolates matching sequences in the mdh library. 146 sequences of the 645bp mdh fragment from five host sources were translated into protein sequence and aligned. Seven unique Mdh protein sequences, which contained eight polymorphic sites, were identified. Six of the polymorphic sites were in the NAD+ binding domain and two were in the catalytic domain. All of the polymorphic sites were located in surface exposed regions of the protein. None of the non-silent mutations of the Mdh protein were in the 150bp mdh target. The advantages and disadvantages of the assay compared to established source tracking methods are discussed.

Animals↗

PubMed2005

Cardiovascular interventional MR imaging: a new road for therapy and repair in the heart.

Over the last 5 years, interventional MR imaging has been fertile ground for research. Real-time MR imaging, combined with recent advances in other MR imaging modalities such as perfusion imaging and intravascular imaging, has opened up new paths for cardiac therapy. The recent reports on cardiac stem cell therapy guided and monitored by MR imaging suggest that we are already seeing the establishment of an important role for cardiac MR imaging in cardiac restoration. The collaborative effort from a multidisciplinary team of basic biologists, engineers, and clinicians will refine stem cell incubation and labeling for MR-guided transcatheter endomyocardial injections, and this in turn may facilitate new studies in humans. Several groups have demonstrated in animal studies the feasibility of MR-guided catheter interventions for the treatment of congenital heart disease and arrythmia therapy. Hence, applications in humans remain the challenge for the next years. Although there have been first reports of cardiac catheterizations in humans by combined use of x-ray fluoroscopy and MR imaging, there are no reports in the literature suggesting that active tracking methods by MR imaging have been applied to humans. Safety issues (namely, heating of catheters and wires) hamper clinical use, particularly in infants and children. Current reports are promising that these limitations will be overcome in the near future and will eventually reduce x-ray usage during catheterization. In its current state, cardiac MR imaging offers a unique opportunity to investigate new therapeutic strategies for the treatment of congenital and acquired heart disease.

Cardiac Catheterization↗

PubMed2005

Automated video analysis of age-related motor deficits in monkeys using EthoVision.

Previous studies comparing age-related changes in locomotor function in nonhuman primates have generally relied on subjective human observations or rudimentary infrared motion sensors. Here, we used the automated video-tracking system EthoVision to objectively quantify locomotor activity in 6 young, 6 middle-aged and 12 aged female rhesus monkeys. The video records were analyzed for distance traveled, movement speed and vertical activity. Our results showed that the young monkeys (4.9 +/- 0.1 years old) traveled twice the distance and moved 48% faster than the middle-aged monkeys (15.7 +/- 0.5 years old), and traveled thrice the distance and moved 67% faster than the aged monkeys (26.3 +/- 0.9 years old). In addition, young monkeys were vertically more active (20/60 min) than both the middle-aged (7/60 min) and the aged (1/60 min) monkeys. Furthermore, the locomotor performance of the individual animals significantly correlated with increasing age for all three measures. We conclude that EthoVision is a reliable and objective tracking method for detecting age-related differences in locomotor movements in rhesus macaques, and possibly in humans.

Aging↗