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Biomedical subjects

M R Bailey

Publications and source records attributed to M R Bailey.

At least 19 recordsLinked to original sources

Strategies for improved shock wave lithotripsy.

Research in lithotripsy that started with the effort to characterize acute shock wave damage to the kidney has led to advances on several fronts, including discovery of strategies that have improved clinical treatment. It is appreciated now that shock wave trauma is primarily a vascular lesion, that injury is dose dependent, and that hemorrhage can be severe and can lead to a permanent loss of functional renal mass. Studies of the renal functional response to lithotripsy have shown that shock wave treatment triggers vasoconstriction in the kidney. This finding has been turned to advantage, and it is now known that when treatment is begun using low amplitude pulses, subsequent high amplitude shock waves are far less damaging. Thus, when shock waves are delivered judiciously, treatment can have a protective effect. The finding that cavitation is a key mechanism in vessel rupture has led to the development of novel experimental methods of shock wave delivery that can suppress bubble expansion and minimize tissue damage. Progress has also been made in understanding the physical mechanisms involved in stone comminution, and it is seen that the forces generated by cavitation, shear stress and circumferential squeezing act synergistically to fragment stones. Recent work suggests that a broad focal zone may be an advantage, allowing stones to be broken with lower amplitude pulses. Cavitation has been shown to play a critical role in reducing stone fragments to a size that can be voided. Cavitation is also the factor that limits the rate at which treatment can be performed, as stones break significantly better at slow rate than at fast ratean observation from basic research that is now appreciated in clinical practice. The current environment in lithotripsy research is encouraging. There is great interest in developing new technology, and in finding ways to improve how lithotripsy is performed.

Animals↗

Radionuclide biokinetics database (RBDATA-EULEP): an update.

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.

Body Burden↗

Improved recovery of active recombinant laccase from maize seed.

Lignolytic enzymes such as laccase have been difficult to over-express in an active form. This paper describes the expression, characterization, and application of a fungal laccase in maize seed. The transgenic seed contains immobilized and extractable laccase. Fifty ppm dry weight of aqueously extractable laccase was obtained, and the remaining solids contained a significant amount of immobilized laccase that was active. Although a portion of the extractable laccase was produced as inactive apoenzyme, laccase activity was recovered by treatment with copper and chloride. In addition to allowing the apoenzyme to regain activity, treatment with copper also provided a partial purification step by precipitating other endogenous corn proteins while leaving >90% of the laccase in solution. The data also demonstrate the application of maize-produced laccase as a polymerization agent. The apparent concentration of laccase in ground, defatted corn germ is approximately 0.20% of dry weight.

Apoenzymes↗

Scientific basis and development of internal dosimetry models (BIODOS).

Assessments of doses and risks to workers and members of the public exposed to radionuclides require biokinetic and dosimetric models which describe the behaviour of the radionuclides and provide tools for dose calculations. The overall objective of BIODOS is to improve the scientific basis of existing models and to provide new or improved models. One part aims to provide models targeting specific uncertainties, including estimates of doses and risks from radionuclides ingested by adults and children; estimates of the transfer of radionuclides to breast milk and doses to infants; development of systemic models to improve the interpretation of bioassays; and studies of the importance of heterogeneous distribution of dose within tissues and cells. The other part forms a comprehensive research programme on the inhalation of radionuclides and addresses four areas of uncertainty, namely ultrafine particles, inter-subject variation, absorption into blood and clearance mechanisms.

Adult↗

RBDATA-EULEP: providing information to improve internal dosimetry.

The overall aim of the concerted action RBDATA-EULEP is to provide information to improve the assessments of intakes of radionuclides and of the resulting doses. This involves a review of the behaviour of radionuclides following intake, and the transfer of expertise on methodology by organising small training workshops. The main activity is the development of an electronic database, effectively an annotated bibliography, but the electronic format used facilitates extension, updating and information retrieval. It consists of linked tables of references and experiments, with details and comments on the materials, procedures and results. By June 2002 it contained information on 524 inhalation, 282 ingestion and 164 injection experiments from 391 references. It will be extended, and Internet access provided. Prospective users include groups developing standards for internal dosimetry, scientists conducting research on radionuclide biokinetics and health physicists assessing the consequences of accidental intakes.

Body Burden↗

Practical application of the ICRP Human Respiratory Tract Model.

The ICRP Publication 66 Human Respiratory Tract Model (HRTM) has been applied to calculate dose coefficients and bioassay functions using default values of parameters relating to the material and the subjects. The ICRP Task Group on Internal Dosimetry (INDOS) has developed a guidance document on application of the HRTM in situations where using specific information can improve dose assessments. INDOS is now revising the worker exposure documents (ICRP Publications 68 and 78). Application of the HRTM requires a review of the lung-to-blood absorption characteristics of inhaled radionuclides. Where appropriate, compound-specific absorption parameter values will be derived, and other compounds will be assigned to default Types using current information. Although no major changes to the HRTM are envisaged, this revision provides an opportunity for some refining and updating in the light of experience and new information.

Aerosols↗

Determination of the physical and chemical properties, biokinetics, and dose coefficients of uranium compounds handled during nuclear fuel fabrication in France.

The introduction of new ICRP recommendations, especially the new Human Respiratory Tract Model (HRTM) in ICRP Publication 66 led us to focus on some specific parameters related to industrial uranium aerosols collected between 1990 and 1999 at French nuclear fuel fabrication facilities operated by COGEMA, FBFC, and the CEA. Among these parameters, the activity median aerodynamic diameter (AMAD), specific surface area (SSA), and parameters describing absorption to blood f(r), s(r) and s(s) defined in ICRP Publication 66 were identified as the most relevant influencing dose assessment. This study reviewed the data for 25 pure and impure uranium compounds. The average value of AMAD obtained was 5.7 microm (range 1.1-8.5 microm), which strongly supports the choice of 5 microm as the default value of AMAD for occupational exposures. The SSA varied between 0.4 and 18.3 m2 g(-1). For most materials, values of the absorption parameters f(r), s(r), and s(s) derived from the in vitro experiments were generally consistent with those derived from the in vivo experiments. Using average values for each pure compound allowed us to classify UO2 and U3O8 as Type S, mixed oxides, UF4, UO3 and ADU as Type M, and UO4 as Type F based on the ICRP Publication 71 criteria. Dose coefficients were also calculated for each pure compound, and average values for each type of pure compound were compared with those derived using default values. Finally, the lung retention kinetics and urinary excretion rates for inhaled U03 were compared using material-specific and default absorption parameters, in order to give a practical example of the application of this study.

Adsorption↗

Plant-based vaccines: unique advantages.

Numerous studies have shown that viral epitopes and subunits of bacterial toxins can be expressed and correctly processed in transgenic plants. The recombinant proteins induce immune responses and have several benefits over current vaccine technologies, including increased safety, economy, stability, versatility and efficacy. Antigens expressed in corn are particularly advantageous since the seed can be produced in vast quantities and shipped over long distances at ambient temperature, potentially allowing global vaccination. We have expressed the B-subunit of Escherichia coli heat-labile enterotoxin and the spike protein of swine transmissible gastroenteritis virus at high levels in corn, and demonstrate that these antigens delivered in the seed elicit protective immune responses.

Animals↗

Real-time visualization of high-intensity focused ultrasound treatment using ultrasound imaging.

High-intensity focused ultrasound (HIFU) and conventional B-mode ultrasound (US) imaging were synchronized to develop a system for real-time visualization of HIFU treatment. The system was tested in vivo in pig liver. The HIFU application resulted in the appearance of a hyperechoic spot at the focus that faded gradually after cessation of HIFU exposure. The duration of HIFU exposure needed for a hyperechoic spot to appear, was inversely related to the HIFU intensity. The threshold intensity required to produce a hyperechoic spot in liver in < 1 s was 970 W/cm(2), in situ. At this HIFU dose, no immediate cellular damage was observed, providing a potential for pretreatment targeting. The real-time visualization method was used in hemostasis of actively bleeding internal pelvic vessels, allowing targeting and monitoring of successful treatment. Real-time US imaging may provide a useful tool for image-guided HIFU therapy.

Animals↗

Use of overpressure to assess the role of bubbles in focused ultrasound lesion shape in vitro.

Overpressure--elevated hydrostatic pressure--was used to assess the role of gas or vapor bubbles in distorting the shape and position of a high-intensity focused ultrasound (HIFU) lesion in tissue. The shift from a cigar-shaped lesion to a tadpole-shaped lesion can mean that the wrong area is treated. Overpressure minimizes bubbles and bubble activity by dissolving gas bubbles, restricting bubble oscillation and raising the boiling temperature. Therefore, comparison with and without overpressure is a tool to assess the role of bubbles. Dissolution rates, bubble dynamics and boiling temperatures were determined as functions of pressure. Experiments were made first in a low-overpressure chamber (0.7 MPa maximum) that permitted imaging by B-mode ultrasound (US). Pieces of excised beef liver (8 cm thick) were treated in the chamber with 3.5 MHz for 1 to 7 s (50% duty cycle). In situ intensities (I(SP)) were 600 to 3000 W/cm(2). B-mode US imaging detected a hyperechoic region at the HIFU treatment site. The dissipation of this hyperechoic region following HIFU cessation corresponded well with calculated bubble dissolution rates; thus, suggesting that bubbles were present. Lesion shape was then tested in a high-pressure chamber. Intensities were 1300 and 1750 W/cm(2) ( +/- 20%) at 1 MHz for 30 s. Hydrostatic pressures were 0.1 or 5.6 MPa. At 1300 W/cm(2), lesions were cigar-shaped, and no difference was observed between lesions formed with or without overpressure. At 1750 W/cm(2), lesions formed with no overpressure were tadpole-shaped, but lesions formed with high overpressure (5.6 MPa) remained cigar-shaped. Data support the hypothesis that bubbles contribute to the lesion distortion.

Animals↗

Use of a dual-pulse lithotripter to generate a localized and intensified cavitation field.

Localizing cavitation to the kidney stone in extracorporeal shock wave lithotripsy may be desirable since cavitation appears to play a major role in both stone comminution and renal tissue damage. A method has been developed to localize and intensify cavitation damage in vitro. Cavitation fields in water were filmed with a high-speed digital video camera. In a conventional lithotripter (CL), the shock wave produced by a single source creates a 2 x 10 cm cylindrical cloud of bubbles in water. Bubbles in the CL field collapse simultaneously along the focal axis to produce a nearly uniform 1-mm x 8-cm line of pits in 25-microm-thick aluminum foil. Our dual-pulse lithotripter (DPL) uses two shock wave sources, facing each other, confocal, and triggered simultaneously to create a 4 x 5 cm cylindrical cloud of bubbles that collapse over a range of times and strengths such that the greatest pit damage on foils is contained within a few square millimeters of the focus. The time for bubbles to grow and collapse was measured with a focused hydrophone and compared with calculations based on the Gilmore equation. Pressure doubling due to synchronous arrival of the two pulses at the focus created increased bubble growth and increased foil pit depth. Asynchronous timing between the two pulses elsewhere in the DPL field resulted in disruption of radial dynamics and negligible pitting to foils. Translation of bubbles was also investigated, both numerically and experimentally. While net translation was calculated to be <0.3 mm in all cases, the rapid acceleration of bubbles in a small region may contribute to their premature destruction in that region. Overall, radial dynamics were found to be largely responsible for the observed pattern of cavitation in the dual-pulse lithotripsy field.

Acoustics↗

A BAC-based physical map of the major autosomes of Drosophila melanogaster.

We constructed a bacterial artificial chromosome (BAC)-based physical map of chromosomes 2 and 3 of Drosophila melanogaster, which constitute 81% of the genome. Sequence tagged site (STS) content, restriction fingerprinting, and polytene chromosome in situ hybridization approaches were integrated to produce a map spanning the euchromatin. Three of five remaining gaps are in repeat-rich regions near the centromeres. A tiling path of clones spanning this map and STS maps of chromosomes X and 4 was sequenced to low coverage; the maps and tiling path sequence were used to support and verify the whole-genome sequence assembly, and tiling path BACs were used as templates in sequence finishing.

Animals↗

A dual passive cavitation detector for localized detection of lithotripsy-induced cavitation in vitro.

A passive cavitation detector (PCD) identifies cavitation events by sensing acoustic emissions generated by the collapse of bubbles. In this work, a dual passive cavitation detector (dual PCD), consisting of a pair of orthogonal confocal receivers, is described for use in shock wave lithotripsy. Cavitation events are detected by both receivers and can be localized to within 5 mm by the nature of the small intersecting volume of the focal areas of the two receivers in association with a coincidence detection algorithm. A calibration technique, based on the impulse response of the transducer, was employed to estimate radiated pressures at collapse near the bubble. Results are presented for the in vitro cavitation fields of both a clinical and a research electrohydraulic lithotripter. The measured lifetime of the primary growth-and-collapse of the cavitation bubbles increased from 180 to 420 microseconds as the power setting was increased from 12 to 24 kV. The measured lifetime compared well with calculations based on the Gilmore-Akulichev formulation for bubble dynamics. The radiated acoustic pressure 10 mm from the collapsing cavitation bubble was measured to vary from 4 to 16 MPa with increasing power setting; although the trends agreed with calculations, the predicted values were four times larger than measured values. The axial length of the cavitation field correlated well with the 6-dB region of the acoustic field. However, the width of the cavitation field (10 mm) was significantly narrower than the acoustic field (25 mm) as bubbles appeared to be drawn to the acoustic axis during the collapse. The dual PCD also detected signals from "rebounds," secondary and tertiary growth-and-collapse cycles. The measured rebound time did not agree with calculations from the single-bubble model. The rebounds could be fitted to a Rayleigh collapse model by considering the entire bubble cloud as an effective single bubble. The results from the dual PCD agreed well with images from high-speed photography. The results indicate that single-bubble theory is sufficient to model lithotripsy cavitation dynamics up to time of the main collapse, but that upon collapse bubble cloud dynamics becomes important.

Auditory Perception↗

Effect of macroscopic air bubbles on cell lysis by shock wave lithotripsy in vitro.

In studies of cells or stones in vitro, the material to be exposed to shock waves (SWs) is commonly contained in plastic vials. It is difficult to remove all air bubbles from such vials. Because SWs reflect at an air-fluid interface, and because existing gas bubbles can serve as nuclei for cavitation events, we sought to determine in our system whether the inclusion of small, visible bubbles in the specimen vial has an effect on SW-induced cell lysis. We found that even small bubbles led to increased lysis of red blood cells (1- to 3-mm diameter bubbles, 9.8+/-0.5% lysis, n = 7; no bubbles, 4.4+/-0.8%, n = 4), and that the degree of lysis increased with bubble size. Damage could not be reduced by centrifuging the cells to the opposite end of the vial, away from the bubble. B-scan ultrasound imaging of blood in polypropylene pipette bulbs showed that, with each SW, bubbles were recruited from the air interface, mixing throughout the fluid volume, and these appeared to serve as nuclei for increased echogenicity during impact by subsequent SWs; thus, bubble effects in vials could involve the proliferation of cavitation nuclei from existing bubbles. Whereas injury to red blood cells was greatly increased by the presence of bubbles in vials, lytic injury to cultured epithelial cells (LLC-PK1, which have a more complex cytoarchitecture than red blood cells) was not increased by the presence of small air bubbles. This suggests different susceptibility to SW damage for different types of cells. Thus, the presence of even a small air bubble can increase SW-induced cell damage, perhaps by increasing the number of cavitation nuclei throughout the vial, but this effect is variable with cell type.

Epithelial Cells↗

Effect of high-intensity focused ultrasound on whole blood with and without microbubble contrast agent.

Using human whole blood samples with and without contrast agent (CA), we evaluated the effect of exposures to focused, continuous wave (CW) 1.1-MHz ultrasound for durations of 10 ms to 1 s at spatial average intensities of 560 to 2360 W/cm2. Cavitation was monitored with a passive cavitation detector and hemolysis was determined with spectroscopy. In whole blood alone, no significant cavitation, heating or hemolysis was detected at any exposure condition. Conversely, cavitation and hemolysis, but not heating, were detected in whole blood with CA. A CA concentration as low as 0.28 microL CA per mL whole blood at an intensity of 2360 W/cm2 for 1 s resulted in measurable cavitation and a 6-fold increase in hemolysis compared to shams. Cavitation and hemolysis increased proportional to the concentration of CA and duration of exposure. In samples containing 4.2 microL CA per mL whole blood exposed for 1 s, a threshold was seen at 1750 W/cm2 where cavitation and hemolysis increased 10-fold compared to exposures at lower intensities. HIFU exposure of whole blood containing CA leads to significant hemolysis in vitro and may lead to clinically significant hemolysis in vivo.

Albumins↗

Comparison of electrohydraulic lithotripters with rigid and pressure-release ellipsoidal reflectors. II. Cavitation fields.

Dramatically different cavitation was produced by two separate acoustic pulses that had different shapes but similar duration, frequency content, and peak positive and negative pressure. Both pulses were produced by a Dornier HM-3 style lithotripter: one pulse when the ellipsoidal reflector was rigid, the other when the reflector was pressure release. The cavitation, or bubble action, generated by the conventional rigid-reflector pulse was nearly 50 times longer lived and 3-13 times stronger than that produced by the pressure-release-reflector pulse. Cavitation durations measured by passive acoustic detection and high-speed video agreed with calculations based on the Gilmore equation. Cavitation intensity, or destructive potential, was judged (1) experimentally by the size of pits in aluminum foil detectors and (2) numerically by the calculated amplitude of the shock wave emitted by a collapsing bubble. The results indicate that the trailing positive spike in the pressure-release-reflector waveform stifles bubble growth and mitigates the collapse, whereas the trough after the positive spike in the rigid-reflector waveform triggers inertially driven growth and collapse. The two reflectors therefore provide a tool to compare effects in weakly and strongly cavitating fields and thereby help assess cavitation's role in lithotripsy.

Acoustics↗

Comparison of electrohydraulic lithotripters with rigid and pressure-release ellipsoidal reflectors. I. Acoustic fields.

The most common lithotripter, a Dornier HM-3, utilizes an underwater spark to generate an acoustic pulse and a rigid ellipsoidal reflector to focus the pulse on the kidney stone to be comminuted. The pulse measured in water with a PVDF membrane hydrophone at the external focus of the ellipsoid was a 1-microsecond positive-pressure spike followed by a 3-microsecond negative-pressure trough. When we replaced the rigid reflector in our experimental lithotripter with a pressure-release reflector, the pulse was a 1.6-microsecond trough followed by a 0.6-microsecond positive spike. The waveforms are nearly time inverses (i.e., their spikes and troughs are reversed). The frequency spectra, the maximum peak positive pressures P+ (42 MPa, rigid and 43 MPa, pressure-release), and the maximum peak negative pressures P- (-12 MPa and -14 MPa) are comparable. The maximum P- occurred 20 mm closer to the reflector than did the maximum P+, for both reflectors. However, the spatial maxima of the peak pressures (P+ and P-) produced by the pressure-release reflector were located 20 mm nearer to the reflector than those produced by the rigid reflector. Qualitative explanation of the waveforms and the location of pressure maxima as well as comparison to previous theoretical and experimental results is given. The alternate waveform produced by the pressure-release reflector may be a tool in determining the role of cavitation in lithotripsy because cavitation is highly sensitive to waveform.

Acoustics↗