PubMed Health⌕ Search

Biomedical subjects

Michael B Smith

Publications and source records attributed to Michael B Smith.

At least 19 recordsLinked to original sources
PubMed2007

Prospective comparison of R-mix shell vial system with direct antigen tests and conventional cell culture for respiratory virus detection.

BACKGROUND AND OBJECTIVES: Conventional cell culture (CC) has limited clinical utility as a result of the extended incubation period often required for virus isolation. Alternative methodologies have been introduced in an effort to improve turnaround times. One such system, the R-mix shell vial is discussed herein. The study objectives were: (a) to establish R-mix testing parameters as compared to direct antigen testing (DAT) and CC, and (b) to assess technical aspects and cost of R-mix in a high volume clinical virology laboratory. STUDY DESIGN: A prospective analysis of respiratory samples submitted to the clinical virology laboratory between November 2004 and April 2005 was performed. All specimens were inoculated onto R-mix shell vials (SV) and CC tubes; and a subset also underwent DAT for influenza A and B and/or RSV. A retrospective estimated cost analysis was made. RESULTS: A total of 563 samples were included in the study, which collectively revealed a total of 207 viruses. Sensitivity of R-mix for seven major respiratory viruses ranged from 45% to 83% compared to CC and DAT, while mean time to detection (TTD) varied from 1.1 to 1.4 days. In addition to these viruses, 23 picornaviruses, 11 CMV isolates and 5 HSV isolates were detected by CC alone. CONCLUSIONS: The R-mix system has similar sensitivity as CC for the detection of parainfluenza 1-3 and influenza A/B while dramatically reducing the TTD. Furthermore, it is significantly more sensitive and produces more timely results for RSV than CC; yet, neither method offers a diagnostic benefit over rapid DAT for RSV detection. The sensitivity of R-mix for adenovirus appears to be significantly lower than that of CC. Lastly, methodologies other than R-mix must remain in place under circumstances where identification of other potential viral respiratory pathogens, including herpesviruses and picornaviruses, is desired.

Adenoviruses, Human↗
PubMed2006

A diet-induced mouse model for glutaric aciduria type I.

In the autosomal recessive human disease, glutaric aciduria type I (GA-1), glutaryl-CoA dehydrogenase (GCDH) deficiency disrupts the mitochondrial catabolism of lysine and tryptophan. Affected individuals accumulate glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in the serum and often suffer acute striatal injury in childhood. Prior attempts to produce selective striatal vulnerability in an animal model have been unsuccessful. We hypothesized that acute striatal injury may be induced in GCDH-deficient (Gcdh-/-) mice by elevated dietary protein and lysine. Here, we show that high protein diets are lethal to 4-week-old and 8-week-old Gcdh-/- mice within 2-3 days and 7-8 days, respectively. High lysine alone resulted in vasogenic oedema and blood-brain barrier breakdown within the striatum, associated with serum and tissue GA accumulation, neuronal loss, haemorrhage, paralysis, seizures and death in 75% of 4-week-old Gcdh-/- mice after 3-12 days. In contrast, most 8-week-old Gcdh-/- mice survived on high lysine, but developed white matter lesions, reactive astrocytes and neuronal loss after 6 weeks. Thus, the Gcdh-/- mouse exposed to high protein or lysine may be a useful model of human GA-1 including developmentally dependent striatal vulnerability.

Amino Acid Metabolism, Inborn Errors↗
PubMed2006

Structures and biological activities of novel phosphatidylethanolamine lipids of Porphyromonas gingivalis.

The Gram-negative periodontal pathogen Porphyromonas gingivalis synthesizes several classes of novel phosphorylated complex lipids, including the recently characterized phosphorylated dihydroceramides. These sphingolipids promote the interleukin-1 (IL-1)-mediated secretion of inflammatory mediators from fibroblasts, including prostaglandin E2 and 6-keto prostaglandin F2alpha, and alter gingival fibroblast morphology in culture. This report demonstrates that one additional class of phosphorylated complex lipids of P. gingivalis promotes IL-1-mediated secretory responses and morphological changes in cultured fibroblasts. Structural characterization identified the new phospholipid class as 1,2-diacyl phosphatidylethanolamine, which substituted predominantly with isobranched C15:0 and C13:0 fatty acids. The isobranched fatty acids, rather than unbranched fatty acids, and the phosphoethanolamine head group were identified as the essential structural elements required for the promotion of IL-1-mediated secretory responses. These structural components are also observed in specific phosphorylated sphingolipids of P. gingivalis and likely contribute to the biological activity of these substances, in addition to the phosphatidylethanolamine lipids described in this report.

6-Ketoprostaglandin F1 alpha↗
PubMed2006

Manipulation of image intensity distribution at 7.0 T: passive RF shimming and focusing with dielectric materials.

PURPOSE: To investigate the effects of high dielectric material padding on RF field distribution in the human head at 7.0 T, and demonstrate the feasibility and effectiveness of RF passive shimming and focusing with such an approach. MATERIALS AND METHODS: The intensity distribution changes of gradient-recalled-echo (GRE) and spin-echo (SE) images of a human head acquired with water pads (dielectric constant = 78) placed in specified configurations around the head at 7.0 T were evaluated and compared with computer simulation results using the finite difference time domain (FDTD) method. The contributions to the B(1) field distribution change from the displacement current and conductive current of a given configuration of dielectric padding were determined with computer simulations. RESULTS: MR image intensity distribution in the human head with an RF coil at 7.0 T can be changed drastically by placing water pads around the head. Computer simulations reveal that the high permittivity of water pads results in a strong displacement current that enhances image intensity in the nearby region and alters the intensity distribution of the entire brain. CONCLUSION: The image intensity distribution in the human head at ultra-high field strengths can be effectively manipulated with high permittivity padding. Utilizing this effect, the B(1) field inside the human head of a given RF coil can be adjusted to reduce the B(1) field inhomogeneity artifact associated with the wave behavior (RF passive shimming) or to locally enhance the signal-to-noise ratio (SNR) in targeted regions of interest (ROIs; RF field focusing).

Brain↗
PubMed2006

Consideration of magnetically-induced and conservative electric fields within a loaded gradient coil.

We present a method to calculate the electric (E)-fields within and surrounding a human body in a gradient coil, including E-fields induced by the changing magnetic fields and "conservative" E-fields originating with the scalar electrical potential in the coil windings. In agreement with previous numerical calculations, it is shown that magnetically-induced E-fields within the human body show no real concentration near the surface of the body, where nerve stimulation most often occurs. Both the magnetically-induced and conservative E-fields are shown to be considerably stronger just outside the human body than inside it, and under some circumstances the conservative E-fields just outside the body can be much larger than the magnetically-induced E-fields there. The order of gradient winding and the presence of conductive RF shield can greatly affect the conservative E-field distribution in these cases. Though the E-fields against the outer surface of the body are not commonly considered, understanding gradient E-fields may be important for reasons other than peripheral nerve stimulation (PNS), such as potential interaction with electrical equipment.

Computer Simulation↗
PubMed2006

Factors influencing flip angle mapping in MRI: RF pulse shape, slice-select gradients, off-resonance excitation, and B0 inhomogeneities.

To understand the various effects that influence actual flip angles, and correct for these effects, it is important to precisely quantify the MRI parameters (such as T1, T2, and perfusion). In this paper actual flip angle maps are calculated using a conventional gradient-echo (GRE) sequence with different radiofrequency (RF) pulse shapes (Gaussian, sinc, and truncated-sinc), slice-selection gradients, off-resonance excitations, and B0 field inhomogeneities. The experimental results demonstrate that RF pulse shapes significantly affect the flip angle distribution and calibration factors. Off-resonance RF excitations, B0 nonuniformities, and slice-selection gradients can lead to degradations in the signal intensities of the images used to map the flip angle, and potentially introduce a bias and increased variance in the measured flip angles.

Algorithms↗
PubMed2006

Exploring the limits of RF shimming for high-field MRI of the human head.

Several methods have been proposed for overcoming the effects of radiofrequency (RF) magnetic field inhomogeneity in high-field MRI. Some of these methods rely at least in part on the ability to independently control magnitude and phase of different drives in either one multielement RF coil or in different RF coils in a transmit array. The adjustment of these drive magnitudes and phases alone to create uniform RF magnetic (B(1)) fields has been called RF shimming, and has certain limits at every frequency as dictated by possible solutions to Maxwell's equations. Here we use numerical calculations to explore the limits of RF shimming in the human head. We found that a 16-element array can effectively shim a single slice at frequencies up to 600 MHz and the whole brain at up to 300 MHz, while an 80-element array can shim the whole brain at up to 600 MHz.

Computer Simulation↗
PubMed2006

Use of the Coccidioides posadasii Deltachs5 strain for quality control in the ACCUPROBE culture identification test for Coccidioides immitis.

Coccidioides posadasii Deltachs5 is a strain that is excluded from the select agent list. Sixteen assays using test reagents from three different ACCUPROBE Coccidioides immitis culture identification test lots had an average of 132,998 relative light units (RLU), which is well beyond the 50,000-RLU positive cutoff value for the test. Coccidioides posadasii Deltachs5 is a satisfactory quality control isolate in the ACCUPROBE culture identification test for Coccidioides immitis.

Animals↗
PubMed2005

Neuroinflammation and both cytotoxic and vasogenic edema are reduced in interleukin-1 type 1 receptor-deficient mice conferring neuroprotection.

BACKGROUND AND PURPOSE: Interleukin-1 (IL-1) is a proinflammatory cytokine implicated in multiple neurodegenerative diseases, including stroke. However, to date, there is no consensus regarding which receptor(s) mediates the detrimental effects of IL-1. We hypothesized that abrogating IL-1 type 1 receptor (IL-1R1) signaling would reduce edema, chemokine expression, and leukocyte infiltration; lower levels of iNOS; and, consequently, decrease free radical damage after mild hypoxia/ischemia (H/I), thus preserving brain cells. METHODS: IL-1R1 null mice and wild-type mice were subjected to a mild H/I insult. MRI was used to measure the area affected at 30 minutes and 48 hours after H/I. An RNAse protection assay was used to evaluate changes in chemokine mRNA expression. RT-PCR was used to assess inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase mRNA levels. Immunohistochemistry was used to assess leukocyte infiltration. Western blots were used to assess iNOS and glutamate aspartate transporter protein levels. RESULTS: IL-1R1 null mice had reduced cytotoxic and vasogenic edema. The volume of hyperintense signal on T2-weighted images was reduced on average by 90% at 48 hours after H/I. The induction of multiple chemokine mRNAs was significantly reduced in IL-1R1 null mice compared with wild-type mice at 18 and 72 hours after H/I, which correlated with fewer infiltrating CD3+ leukocytes. Levels of iNOS protein and mRNA (but not glutamate aspartate transporter) were significantly reduced in the IL-1R1 mouse brain. CONCLUSIONS: These findings indicate that abrogating IL-1R1 signaling could protect brain cells subsequent to a mild stroke by reducing edema and immune cell recruitment, as well as by limiting iNOS-mediated free radical damage.

Amino Acid Transport System X-AG↗
PubMed2005

Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076].

BACKGROUND: Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay. METHODS: The study was a randomized, double-blind controlled trial of aerosolized racemic epinephrine compared to salbutamol every one to 4 hours in previously well children aged 6 weeks to < or = 2 years of age hospitalized with bronchiolitis. The primary outcome was symptom improvement as measured by the Respiratory Distress Assessment Instrument (RDAI); secondary outcomes were length of stay in hospital, adverse events, and report of symptoms by structured parental telephone interview one week after discharge. RESULTS: 62 children with a mean age of 6.4 months were enrolled; 80% of children had Respiratory Syncytial Virus (RSV). Racemic epinephrine resulted in significant improvement in wheezing and the total RDAI score on day 2 and over the entire stay (p < 0.05). The mean LOS in the epinephrine arm was 2.6 days (95% CI 2, 3.2) v. 3.4 days in those in the salbutamol group (95% CI 2.6, 4.2) (p > 0.05). Adverse events were not significantly different in the two arms. At one week post-discharge, over half of parents reported that their child still had a respiratory symptom and 40% had less than normal feeding. CONCLUSION: Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay. Morbidity associated with bronchiolitis as identified by parents persists for at least one week after hospital discharge in most infants.

Administration, Inhalation↗
PubMed2005

Central brightening due to constructive interference with, without, and despite dielectric resonance.

PURPOSE: To aid in discussion about the mechanism for central brightening in high field magnetic resonance imaging (MRI), especially regarding the appropriateness of using the term dielectric resonance to describe the central brightening seen in images of the human head. MATERIALS AND METHODS: We present both numerical calculations and experimental images at 3 T of a 35-cm-diameter spherical phantom of varying salinity both with one surface coil and with two surface coils on opposite sides, and further numerical calculations at frequencies corresponding to dielectric resonances for the sphere. RESULTS: With two strategically placed surface coils it is possible to create central brightening even when one coil alone excites an image intensity pattern either bright on one side only or bright on both sides with central darkening. This central brightening can be created with strategic coil placement even when the resonant pattern would favor central darkening. Results in a conductive sample show that central brightening can similarly be achieved in weakly conductive dielectric materials where any true resonances would be heavily damped, such as in human tissues. CONCLUSION: Constructive interference and wavelength effects are likely bigger contributors to central brightening in MR images of weakly conductive biological samples than is true dielectric resonance.

Electromagnetic Fields↗
PubMed2005

Measurement and correction of transmitter and receiver induced nonuniformities in vivo.

Signal intensity nonuniformities in high field MR imaging limit the ability of MRI to provide quantitative information and can negatively impact diagnostic scan quality. In this paper, a simple method is described for correcting these effects based on in vivo measurement of the transmission field B1+ and reception sensitivity maps. These maps can be obtained in vivo with either gradient echo (GE) or spin echo (SE) imaging sequences, but the SE approach exhibits an advantage over the GE approach for correcting images over a range of flip angles. In a uniform phantom, this approach reduced the ratio of the signal SD to its mean from around 30% before correction to approximately 6% for the SE approach and 9% for the GE approach after correction. The application of the SE approach for correcting intensity nonuniformities is demonstrated in vivo with human brain images obtained using a conventional spin echo sequence at 3.0 T. Furthermore, it is also shown that this in vivo B1+ and reception sensitivity mapping can be performed using segmented echo planar imaging sequences providing acquisition times of less than 2 min. Although the correction presented here is demonstrated with a simultaneous transmit and receive volume coil, it can be extended to the case of separate transmission and reception coils, including surface and phase array coils.

Algorithms↗
PubMed2005

Hexagonal zero mode TEM coil: a single-channel coil design for imaging multiple small animals.

A novel hexagonal coil design for simultaneous imaging of multiple small animals is presented. The design is based on a coaxial cavity and utilizes the magnetic field formed between two coaxial conductors with hexagonal cross-sections. An analytical solution describing the B(1) field between conductors of the hexagonal coil was found from the Biot-Savart law. Both experimental results and analytical calculations showed a variation in the B(1) field within the imaging region of less than 10%. Numerical calculations predicted approximately 35% improvement in B(1) field homogeneity with the hexagonal coil design compared to a cylindrical coaxial cavity design. The experimentally-measured signal-to-noise ratio (SNR) of the hexagonal coil loaded with six 50-mM phantoms was only 4-5% lower than that of a single parallel plate resonator loaded with one phantom. In vivo spin-echo (SE) images of six 7-day-old rat pups acquired simultaneously demonstrated sufficient SNR for microimaging. The construction scheme of the coil, simple methods for tuning and matching, and an anesthesia device and animal holder designed for the coil are described. The hexagonal coil design utilizes a single receiver and allows for simultaneous imaging of six small animals with no significant compromise in SNR.

Animals↗
PubMed2005

B(1) destructive interferences and spatial phase patterns at 7 T with a head transceiver array coil.

RF behavior in the human head becomes complex at ultrahigh magnetic fields. A bright center and a weak periphery are observed in images obtained with volume coils, while surface coils provide strong signal in the periphery. Intensity patterns reported with volume coils are often loosely referred to as "dielectric resonances," while modeling studies ascribe them to superposition of traveling waves greatly dampened in lossy brain tissues, raising questions regarding the usage of this term. Here we address this question experimentally, taking full advantage of a transceiver coil array that was used in volume transmit mode, multiple receiver mode, or single transmit surface coil mode. We demonstrate with an appropriately conductive sphere phantom that destructive interferences are responsible for a weak B(1) in the periphery, without a significant standing wave pattern. The relative spatial phase of receive and transmit B(1) proved remarkably similar for the different coil elements, although with opposite rotational direction. Additional simulation data closely matched our phantom results. In the human brain the phase patterns were more complex but still exhibited similarities between coil elements. Our results suggest that measuring spatial B(1) phase could help, within an MR session, to perform RF shimming in order to obtain more homogeneous B(1) in user-defined areas of the brain.

Algorithms↗
PubMed2005

Combination of optimized transmit arrays and some receive array reconstruction methods can yield homogeneous images at very high frequencies.

Image inhomogeneity related to high radiofrequencies is one of the major challenges for high field imaging. This inhomogeneity can be thought of as having 2 radiofrequency-field related contributors: the transmit field distribution and the reception field distribution. Adjusting magnitude and phase of currents in elements of a transmit array can significantly improve flip angle homogeneity at high field. Effective application of some well-known parallel imaging and other receive array post-processing methods removes receptivity patterns from the intensity distribution in the final image, though noise then becomes a function of position in the final image. Here simulations are used to show that, assuming high signal-to-noise ratio, very homogeneous images in the human head can be acquired with the combination of transmit arrays and some receive array reconstruction methods at frequencies as high as 600 MHz.

Algorithms↗
PubMed2005

Interleukin-1 and the interleukin-1 type 1 receptor are essential for the progressive neurodegeneration that ensues subsequent to a mild hypoxic/ischemic injury.

Excessive inflammation has been implicated in the progressive neurodegeneration that occurs in multiple neurological diseases, including cerebral ischemia, and elevated levels of the proinflammatory cytokine interleukin-1 (IL-1) have been shown to exacerbate brain damage, whereas diminishing IL-1 levels limits the extent of injury. However, to date there is no consensus regarding which receptor(s) mediates the detrimental effects of IL-1. Because we have previously demonstrated that signaling through the IL-1 type 1 receptor (IL-1R1) is necessary for microglial activation and because results from other studies have implicated microglia as effectors of neurodegeneration, we hypothesized that inactivating the IL-1R1 would decrease the extent of damage caused by a hypoxic-ischemic (H/I) insult. It is shown that a mild insult initiates progressive neurodegeneration that leads to cystic infarcts, which can be prevented by inactivating the IL-1R1. The IL-1R1 null mice also show preserved sensorimotor function at 1 month's recovery. The mild insult induces multiple proinflammatory cytokines and activates microglia, and these responses are dramatically curtailed in mice lacking the IL-1R1. Importantly, the neuroinflammation precedes the progressive enlargement of the infarct, suggesting that the inflammation is causal rather than a consequence of the brain damage. These findings show that abrogating the inflammation consequent to a mild H/I insult will prevent brain damage and preserve neurological function. Additionally, these data incriminate the IL-1R1 as a master proinflammatory cytokine receptor.

Animals↗
PubMed2005

Functional magnetic resonance imaging study of human olfaction and normal aging.

BACKGROUND: The function of human olfaction declines with advancing age. An important question centers on whether functional alterations to olfactory brain structures accompany age-related behavioral changes. In the present study, we tested the hypothesis that aged adults have intact though reduced activity in the central olfactory system using functional magnetic resonance imaging (fMRI). METHODS: University of Pennsylvania Smell Identification Test (UPSIT) was used to test the smell function of 11 young (23.9 +/- 1.6 years) and 8 aged (66.4 +/- 4.4 years) healthy participants. Then, the participants received fMRI at 3.0 T with lavender and spearmint as stimulants. After fMRI, the participants provided ratings for the odorants' intensity and pleasantness. RESULTS: The average UPSIT score of the aged adults was 34.1 +/- 1.5, which was significantly lower than that of the young adults (37.3 +/- 1.1) (p =.0004). Both age groups showed significant activation in major olfactory brain structures, including the primary olfactory cortex, entorhinal cortex, hippocampus and parahippocampal cortex, thalamus, hypothalamus, orbitofrontal cortex, and insular cortex and its extension into the inferior lateral frontal region. The aged adults showed less brain activity in olfactory structures (p =.022), consistent with lower ratings of odor intensity and UPSIT scores. Activation intensity in bilateral primary olfactory cortex areas and right insular cortex was also comparatively weaker (p <.019). CONCLUSION: Results demonstrate that significant activation in aged adults can be observed in all the olfactory brain structures that are activated in young adults, but with lower activation volume and intensity. This finding provides a necessary baseline for further investigations in olfaction and aging.

Adult↗