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PubMed2005

Soft tissue response of the larynx to silicone, Gore-Tex, and irradiated cartilage implants.

OBJECTIVE: The aim of the study is to compare the efficiency of three different materials (Silicone, Gore-Tex, and irradiated cartilage) used in medialization laryngoplasty. Local tissue reaction to implants in laryngeal skeleton has been examined for this purpose. STUDY DESIGN AND METHODS: In this prospective study, New Zealand rabbits were used. Different materials have been implanted in the paraglottic space of both sides of the larynx to enable a better comparison of the different materials used. Limited medialization was applied. Special care has been taken not to narrow the airway and cause breathing problems. The reaction of the tissue in this region against the materials used has been studied. Each material was implanted 14 times in total. The rabbits were killed 6 months after the implementation to study their larynx. For each material, the fibrous capsule formation, histiocyte infiltration, foreign body giant cell infiltration, eosinophil infiltration, neutrophil infiltration, and lymphoplasmacytic infiltration levels were investigated histologically. RESULTS: Best fibrous capsule formation has been observed around silicone. Allergic reactions and inflammatory responses were minimal for this material. Fibrous capsule formation was more limited with Gore-Tex. Some degree of chronic inflammatory response (in few cases) has been observed against this material. Severe allergic response was observed against irradiated cartilage, and the implant material was resorbed completely in most cases. CONCLUSION: According to histopathologic results of this study (tissue compatibility of three materials), silicone is the most suited material among the study materials for medialization. Gore-Tex can also be used for this purpose. Irradiated cartilage, on the other hand, appears not to be a suitable material for medialization laryngoplasty.

Absorbable Implants↗
PubMed2006

Physical parameters affecting ultrasound/microbubble-mediated gene delivery efficiency in vitro.

Ultrasound (US)/microbubble-mediated gene delivery is a technology with many potential advantages suited to clinical application. Previous studies have demonstrated transfection but many are unsatisfactory in respect to the exposure apparatus, lack of definition of the US field or the limitations on parameters that can be explored using clinical diagnostic US machines. We investigated individual exposure parameters using a system minimising experimental artefacts and allowing control of many parameters of the US field. Using a 1-MHz transducer we systematically varied US parameters, the duration of exposure and the microbubble and DNA concentrations to optimise gene delivery. Delivery was achieved, using lipid microbubbles (SonoVue) and clinically acceptable US exposures, to adherent cells at efficiencies of approximately 4%. The acoustic pressure amplitude (0.25 MPa peak-negative), pulse repetition frequency (1-kHz) and duration of exposure (10 s) were important in optimising gene delivery with minimal impact on cell viability. These findings support the hypothesis that varying the physical parameters of US-mediated gene delivery has an affect on both efficiency and cell viability. These data are the first in terms of their thorough exploration of the US parameter space and will be the basis for more-informed approaches to developing clinical applications of this technology.

Animals↗
PubMed2004

Lensless imaging of magnetic nanostructures by X-ray spectro-holography.

Our knowledge of the structure of matter is largely based on X-ray diffraction studies of periodic structures and the successful transformation (inversion) of the diffraction patterns into real-space atomic maps. But the determination of non-periodic nanoscale structures by X-rays is much more difficult. Inversion of the measured diffuse X-ray intensity patterns suffers from the intrinsic loss of phase information, and direct imaging methods are limited in resolution by the available X-ray optics. Here we demonstrate a versatile technique for imaging nanostructures, based on the use of resonantly tuned soft X-rays for scattering contrast and the direct Fourier inversion of a holographically formed interference pattern. Our implementation places the sample behind a lithographically manufactured mask with a micrometre-sized sample aperture and a nanometre-sized hole that defines a reference beam. As an example, we have used the resonant X-ray magnetic circular dichroism effect to image the random magnetic domain structure in a Co/Pt multilayer film with a spatial resolution of 50 nm. Our technique, which is a form of Fourier transform holography, is transferable to a wide variety of specimens, appears scalable to diffraction-limited resolution, and is well suited for ultrafast single-shot imaging with coherent X-ray free-electron laser sources.

Journal Article↗
PubMed1990

The Edridge-Green lecture vision at low light levels: role of spatial, temporal and contrast filters.

One of the most impressive features of our vision is the fact that we see with good sensitivity over such a large range of light levels. This process is usually termed light adaptation by which it is meant that the sensitivity of individual neurones within the retina automatically adapts to suit the prevailing lighting conditions. Although this is usually thought about in terms of single neurones, its effectiveness is greatly enhanced by the fact that individual neurones have distinctive properties. The fact that individual neurones can be considered as acting as neural filters along the dimensions of size, time, orientation and contrast means that visual information is distributed across the whole neuronal population which in turn plays an important role in extending our dynamic range. In this paper the distributed nature of visual processing is emphasized and its role in extending the range of light levels over which we can see is highlighted.

Adaptation, Ocular↗
PubMed1995

Reflectance spectroscopy of ferric sulfate-bearing montmorillonites as Mars soil analog materials.

Spectroscopic analyses have shown that smectites enhanced in the laboratory with additional ferric species exhibit important similarities to those of the soils on Mars. Ferrihydrite in these chemically treated smectites has features in the visible to near-infrared region that resemble the energies and band strengths of features in reflectance spectra observed for several bright regions on Mars. New samples have been prepared with sulfate as well, because S was found by Viking to be a major component in the surface material on Mars. A suite of ferrihydrite-bearing and ferric sulfate-bearing montmorillonites, prepared with variable Fe3+ and S concentrations and variable pH conditions, has been analyzed using reflectance spectroscopy in the visible and infrared regions, Mössbauer spectroscopy at room temperature and 4 K, differential thermal analysis, and X-ray diffraction. These analyses support the formation of ferrihydrite of variable crystallinity in the ferrihydrite-bearing montmorillonites and a combination of schwertmannite and ferrihydrite in the ferric sulfate-bearing montmorillonites. Small quantities of poorly crystalline or nanophase forms of other ferric materials may also be present in these samples. The chemical formation conditions of the ferrihydrite-bearing and ferric sulfate-bearing montmorillonites influence the character of the low temperature Mössbauer sextets and the visible reflectance spectra. An absorption minimum is observed at 0.88-0.89 micrometers in spectra of the ferric sulfate-bearing samples, and at 0.89-0.92 micrometers in spectra of the ferrihydrate-bearing montmorillonites. Mössbauer spectra of the ferric sulfate-bearing montmorillonites indicate variable concentrations of ferrihydrite and schwertmannite in the interlaminar spaces and along grain surfaces. Dehydration under reduced atmospheric pressure conditions induces a greater effect on the adsorbed and interlayer water in ferrihydrite-bearing montmorillonite than on the water in ferric sulfate-bearing montmorillonite. Reflectance spectra of ferric sulfate-bearing montmorillonite include a strong 3-micrometers band that is more resistant to dry atmospheric conditions than the 3-micrometers band in spectra of similarly prepared ferrihydrite-bearing montmorillonites.

Aluminum Silicates↗
PubMed2000

Fluoroscopically triggered contrast-enhanced 3D MR DSA and 3D time-of-flight turbo MRA of the carotid arteries: first clinical experiences in correlation with ultrasound, x-ray angiography, and endarterectomy findings.

The aim of this article was to obtain initial experiences with fluoroscopically triggered contrast-enhanced (CE) 3D MR DSA with elliptical centric k-space order and 3D time-of-flight (TOF) turbo MRA of the carotid arteries. In this prospective study we examined 16 consecutive patients with suspicion of atherosclerotic disease involving the carotid arteries. Ultrasound was available in all, x-ray angiography in 12, surgical correlation in 9, and intraoperative x-ray angiography in 4 patients. All examinations were done on a 1.5 T unit applying: transverse plain 3D TOF turbo MRA and coronal CE MRA with fluoroscopic triggering. Combining head and neck array coils allowed the visualization of supraaortic arteries from the aortic arch to the circle of Willis. MRA results (maximum intensity projections) were compared with x-ray angiography, ultrasound, and inspection of endarterectomy specimens. Volume rendering was performed in selected cases additionally. Agreement between CE MRA, 3D TOF turbo MRA and x-ray angiography regarding stenoses of the internal and external carotid artery was very good. CE MRA was able to detect correctly intracranial stenoses, but delineation of the aortic arch and proximal common carotid arteries was sometimes reduced. Volume rendering was suited for visualization of MRA images providing a realistic three-dimensional impression. In conclusion, high-resolution fluoroscopically triggered CE MRA as non-invasive technique is another important step on the way to replace invasive x-ray angiography for the evaluation of atherosclerotic carotid artery disease. High resolution 3D TOF turbo MRA might be a helpful adjunct to increase the diagnostic reliability for the carotid bifurcation.

Aged↗
PubMedDate not supplied

Information technology and public health management of disasters--a model for South Asian countries.

This paper highlights the use of information technology (IT) in disaster management and public health management of disasters. Effective health response to disasters will depend on three important lines of action: (1) disaster preparedness; (2) emergency relief; and (3) management of disasters. This is facilitated by the presence of modern communication and space technology, especially the Internet and remote sensing satellites. This has made the use of databases, knowledge bases, geographic information systems (GIS), management information systems (MIS), information transfer, and online connectivity possible in the area of disaster management and medicine. This paper suggests a conceptual model called, "The Model for Public Health Management of Disasters for South Asia". This Model visualizes the use of IT in the public health management of disasters by setting up the Health and Disaster Information Network and Internet Community Centers, which will facilitate cooperation among all those in the areas of disaster management and emergency medicine. The suggested infrastructure would benefit the governments, non-government organizations, and institutions working in the areas of disaster and emergency medicine, professionals, the community, and all others associated with disaster management and emergency medicine. The creation of such an infrastructure will enable the rapid transfer of information, data, knowledge, and online connectivity from top officials to the grassroots organizations, and also among these countries regionally. This Model may be debated, modified, and tested further in the field to suit the national and local conditions. It is hoped that this exercise will result in a viable and practical model for use in public health management of disasters by South Asian countries.

Artificial Intelligence↗
PubMed2005

GenClust: a genetic algorithm for clustering gene expression data.

BACKGROUND: Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering. RESULTS: GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means. CONCLUSION: Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology.

Algorithms↗
PubMed1993

A preliminary report: postoperative fertility assessment in nerve-sparing RPLND patients.

Nerve-sparing RPLND is a procedure suited to patients with clinical stage I nonseminoma. Additionally, nerve-sparing techniques are applicable to patients with higher stage disease. Although ejaculation is reliably preserved with nerve-sparing techniques, the question of these patients' fertility has remained. Fertility was assessed in these patients by two techniques: laboratory analysis of semen and a post-RPLND questionnaire. Semen analyses and DNA histograms suggested fertility in > 70%; in addition, 43 of 53 (81%) patients who have tried to father children post RPLND have been successful. Nerve-sparing RPLND appears to be able to preserve fertility potential in these patients.

DNA, Neoplasm↗
PubMed2004

Implantable flow-through capillary-type microdialyzers for continuous in situ monitoring of environmentally relevant parameters.

In this paper, a simple, flexible, and cost-effective flow-through microdialyzer hyphenated with a miniaturized differential potentiometric detector is proposed for continuous diffusion-controlled sampling of analytes of environmental interest. The analytical performance of the dedicated configuration involving merely a single cellulose regenerated hollow fiber is critically compared with that of commercially available concentric probes commonly exploited for in vivo monitoring of the extracellular space in living tissues and that of large dialysis-based probes furnished with flat membranes. The outstanding feature of the capillary-type design is the ability of adapting the extraction fractions (EF) to the requirements of the assays and flow-through detectors by selection of appropriate membrane length/perfusion rate ratios. Passive sampling under steady-state conditions (EF approximately 100%) has proven feasible for environmentally relevant ions, such as chloride, by perfusing a 3-cm-long capillary with water at a flow rate of 2.0 microL/min. Hence, there is no need for recalibration of the flow setup after implantation of the purpose-made probe. The effect of physical and chemical variables on the diffusive flux is discussed in detail for the various flow-through membrane separation devices assessed. Effective means to attain identical dialysate concentrations of target species under dynamic regime irrespective of the matrix ingredients are also presented. The dedicated microdialyzer features extreme tolerance to high molecular weight interfering matrix compounds (> or =5000 mg/L humic acid) at the 5% interference level, which makes it especially suited for the interference-free potentiometric determination of ionic species in environmental samples containing high levels of organic matter. The potentials of the membrane separation unit were assessed for continuous monitoring of chemical changes in the interstitial/pore water of organic soils via stimulus-response strategies.

Chlorides↗
PubMedDate not supplied

Exploratory chemoinformatic analysis of cell type-selective anticancer drug targeting.

In pharmaceutical development, structure-activity relationship studies aim to identify characteristics of chemical structures associated with well-defined activity end points. While this goal-driven approach is ideally suited for lead development purposes, a more exploration-driven approach is needed to discover cell type-selective drug targeting mechanisms in complex data sets. Growth inhibition profiles across different cancer cell lines are potentially informative with respect to molecular mechanisms targeting the activity of anticancer agents to specific tumor cells, yet only a small number of mechanistic associations between chemical structure and growth inhibition profiles have been discovered to date. Here, we have applied an exhaustive statistical analysis strategy to more than 10000 compounds in the NCI's anticancer agent database to identify molecular substructures associated with specific cytotoxicity signatures against a panel of human tumor-derived cancer cell lines (the Developmental Therapeutics Program 60-cell line panel). Some of the most significant substructures conferring cell type-selective cytotoxic activity include a large family of delocalized lipophilic cations; chloropurines, chloropyrimidines, and thiazoles; organosulfur chelators and organometallic complexes; and an unexpectedly related family of alkyl-lysophospholipids and phosphate prodrugs. Information from cell-based assays and gene expression measurements have been related to substructures represented in the chemical space covered by the library, yielding several candidate targeting mechanisms.

Antineoplastic Agents↗
PubMed1983

Ionic currents in single isolated bullfrog atrial cells.

Enzymatic dispersion has been used to yield single cells from segments of bullfrog atrium. Previous data (Hume and Giles, 1981) have shown that these individual cells are quiescent and have normal resting potentials and action potentials. The minimum DC space constant is approximately 920 microns. The major goals of the present study were: (a) to develop and refine techniques for making quantitative measurements of the transmembrane ionic currents, and (b) to identify the individual components of ionic current which generate different phases of the action potential. Initial voltage-clamp experiments made using a conventional two-microelectrode technique revealed a small tetrodotoxin (TTX)-insensitive inward current. The small size of this current (2.5-3.0 X 10(-10)A) and the technical difficulty of the two-microelectrode experiments prompted the development of a one-microelectrode voltage-clamp technique which requires impalements using a low-resistance (0.5-2 M omega) micropipette. Voltage-clamp experiments using this new technique in isolated single atrial cells reveal five distinct ionic currents: (a) a conventional transient Na+ current, (b) a TTX-resistant transient inward current, carried mainly by Ca++, (c) a component of persistent inward current, (d) a slowly developing outward K+ current, and (e) an inwardly rectifying time-independent background current. The single suction micropipette technique appears well-suited for use in the quantitative study of ionic currents in these cardiac cells, and in other small cells having similar electrophysiological properties.

Animals↗
PubMed2006

Chemical loading into surface water along a hydrological, biogeochemical, and land use gradient: a holistic watershed approach.

Identifying the sources and impacts of organic and inorganic contaminants at the watershed scale is a complex challenge because of the multitude of processes occurring in time and space. Investigation of geochemical transformations requires a systematic evaluation of hydrologic, landscape, and anthropogenic factors. The 1160 km2 Boulder Creek Watershed in the Colorado Front Range encompasses a gradient of geology, ecotypes, climate, and urbanization. Streamflow originates primarily as snowmelt and shows substantial annual variation. Water samples were collected along a 70-km transect during spring-runoff and base-flow conditions, and analyzed for major elements, trace elements, bulk organics, organic wastewater contaminants (OWCs), and pesticides. Major-element and trace-element concentrations were low in the headwaters, increased through the urban corridor, and had a step increase downstream from the first major wastewater treatment plant (WWTP). Boron, gadolinium, and lithium were useful inorganic tracers of anthropogenic inputs. Effluent from the WWTP accounted for as much as 75% of the flow in Boulder Creek and was the largest chemical input. Under both hydrological conditions, OWCs and pesticides were detected in Boulder Creek downstream from the WWTP outfall as well as in the headwater region, and loads of anthropogenic-derived contaminants increased as basin population density increased. This report documents a suite of potential endocrine-disrupting chemicals in a reach of stream with native fish populations showing indication of endocrine disruption.

Colorado↗
PubMed1990

Calculation of site affinity constants and cooperativity coefficients for binding of ligands and/or protons to macromolecules. I. Generation of partition functions and mass balance equations.

The thermodynamics of binding of a ligand A and/or proton H to a macromolecule M is treated by the partition function method. In complex systems, the representation of the equilibria by means of cumulative constants beta PQR used as coefficients in partition functions ZM, ZA, and ZH is ill-suited to least-squares refinement procedures because the cumulative constants are interrelated by common cooperativity functions gamma j(i) and common site affinity constants kappa j. There is therefore the need to express ZM, ZA, ZH as functions of site constants kappa j and cooperativity coefficients bj. This is done by developing an algebra of partition functions based on the following concepts: (i) factorability of partition functions; (ii) binary generating function Jj = (1 + kappa j[Y])i tau for each class j of sites, represented by column (Jj) and row (Jj) vectors; (iii) cooperativity between sites of one class described by functions gamma j(i), represented by diagonal matrices gamma j; (iv) probability of finding microspecies represented by elements of tensor product matrix Ll = (J1)[J2]; (v) statistical factors mij obtained from Newton polynomials, Jj; (vi) power operators Oi', O(i-l)', and O(i tau-l)', transforming vectors Jj; and (vii) operators Oi or O(i-l) indicating tensor products of i or (i-l) vectors Jj. Vectors Jj combined in tensors Ll give rise to both an affinity/cooperativity space and a parallel index space. The partition functions ZM, ZA, and ZH and the total amounts TM, TA, and TH can be obtained as an appropriate sum of elements of matrices Ll, each of which is represented in an index space by a combination p1, p2,...q1, q2,...r1, r2,... of indices ij. From these indices the contribution of that element to partition function ZM, ZA, or ZH and to total amount TM, TA, or TH is calculated in the affinity/cooperativity space as product of factors: [i tau !/i !(i tau-i)!]kappa ij(exp[bj (i-1)i])[X]i, i being any index p, q, r and X any component M, A, or H. Future applications of this algorithm to practical problems of macromolecule-ligand-proton equilibria are outlined.

Binding Sites↗
PubMed2002

Reliable, responsive pacemaking and pattern generation with minimal cell numbers: the crustacean cardiac ganglion.

Investigations of the electrophysiology of crustacean cardiac ganglia over the last half-century are reviewed for their contributions to elucidating the cellular mechanisms and interactions by which a small (as few as nine cells) neuronal network accomplishes extremely reliable, rhythmical, patterned activation of muscular activity-in this case, beating of the neurogenic heart. This ganglion is thus a model for pacemaking and central pattern generation. Favorable anatomy has permitted voltage- and space-clamp analyses of voltage-dependent ionic currents that endow each neuron with the intrinsic ability to respond with rhythmical, patterned impulse activity to nonpatterned stimulation. The crustacean soma and initial axon segment do not support impulse generation but integrate input from stretch-sensitive dendrites and electrotonic and chemically mediated synapses on axonal processes in neuropils. The soma and initial axon produce a depolarization-activated, calcium-mediated, sustained potential, the "driver potential," so-called because it drives a train of impulses at the "trigger zone" of the axon. Extreme reliability results from redundancy and the electrotonic coupling and synaptic interaction among all the neurons. Complex modulation by central nervous system inputs and by neurohormones to adjust heart pumping to physiological demands has long been demonstrated, but much remains to be learned about the cellular and molecular mechanisms of action. The continuing relevance of the crustacean cardiac ganglion as a relatively simple model for pacemaking and central pattern generation is confirmed by the rapidly widening documentation of intrinsic potentials such as plateau potentials in neurons of all major animal groups. The suite of ionic currents (a slowly inactivating calcium current and various potassium currents, with variations) observed for the crustacean cardiac ganglion have been implicated in or proven to underlie a majority of the intrinsic potentials of neurons involved in pattern generation.

Animals↗
PubMed2002

Simplified computation of third-rank image aberrations of electron-optical systems with curved axis.

Using the classical perturbation theory only the image aberrations of second rank of an electron-optical system with a curved axis are easy to obtain. Analytical integral expressions of these second-rank aberrations were already published in German by Plies and Typke (Z. Naturforsch. 33a (1978) 1361, 35a (1980) 566). They employed the eikonal method in the case of arbitrary electrostatic and stationary magnetic fields without space charge and currents in the beam region. Their results are repeated briefly in English and a method is discussed of how a magnetic round lens field can be considered in the case of a system with a single-section symmetry, i.e., an orthogonal system with no torsion of the curved optic axis. Then the important second-rank fundamental trajectories are introduced which are directly related to the integral expressions already given in Plies and Typke (1978). Then the secondary aberrations (obtained by the second step of the successive approximation method) and the complexity of the third-rank aberrations are discussed. After that two new methods are proposed for a simplified calculation of the third-rank image aberrations. Both proposals use the second-rank fundamental trajectories and the second proposed method additionally uses the spatial potential and field achieved by using a three-dimensional field solver. Since these two simplified computation methods are still rather complicated an additional method based on ray tracing is discussed. For this purpose a trajectory equation with respect to the curved optic axis and well suited for numerical integration with high accuracy is derived. This offers the possibility of exact numerical ray tracing of selected and representative axial and field rays. After subtracting from such a ray the known first- and second-rank ray with the same trajectory parameters (aperture, off-axial coordinate, energy deviation) one obtains the complete residual aberration.

Journal Article↗
PubMed1975

Techniques for termination of reverberating spreading depression in rats.

Reverberation of cortical spreading depression (CSD) around a circular obstacle (thermocoagulation lesion) in the frontal cortex of anesthetized rats was elicited by appropriately timed and spaced applications of KCl. The probability of continued reverberation was increased by a pyrrolopyrimidine drug BW 58-271 (10 mg/kg) from 0.93 to 0.98. Three methods of reverberation arrest were tested: a) CSD propagation was blocked by an interfering CSD wave which was initiated in the rear of the reverberating wave, passing through a narrow segment of the circular pathway, and collided with the reverberating wave on the opposite side of the obstacle; b) CSD propagation through a part of the circular pathway was blocked by a 10-min application of 10% MgCl2 on the exposed cortical surface; c) 1-min asphyxia stopped RCSD by increasing the overall refractoriness of cortical tissue. Least reliable was the interference method which stopped reverberation, even with optimum timing, only in 42% of the trials. The magnesium blockade was reliable but slow, the reverberation stopping only 30 min after MgCl2 application. Asphyxia evoked in any phase of the reverberation cycle stopped RCSD reliably and immediately. The results obtained with the interference method confirm the predictions of the mathematical model of impulse reverberation in sheets of excitable tissue. Anoxia seems best suited for practical control of CSD reverberation in functional decortication studies.

Animals↗
PubMed1998

Liposphere local anesthetic timed-release for perineural site application.

PURPOSE: This investigation determines the drug delivery capacity of Lipospheres, which are drug-containing solid-filled vesicles made of triglyceride with a phospholipid outer covering, to release local anesthetic in vitro and to produce sustained peripheral nerve block in vivo. METHODS: The local anesthetic, bupivacaine, was loaded into Lipospheres in several dosage forms, characterized, and measured for in vitro release. In rats, Lipospheres were administered into a large space between muscle layers surrounding the sciatic nerve to assess sensory and motor block in vivo. RESULTS: The particle size of Lipospheres was determined to be between 5 and 15 microm, with over 90% surface phospholopid. Lipospheres released bupivacaine over two days under ideal sink conditions. Liposphere nerve application produced dose-dependent and reversible block. Indeed, sustained local anesthetic block (SLAB) was observed for 1-3 days in various in vivo tests: a) Hind paw withdrawal latency to noxious heat was increased over 50% for 96 hr period after application of 3.6% or 5.6% bupivacaine-Lipospheres. The 3.6% and 5.6% doses were estimated to release bupivacaine at 200 and 311 microg drug/ hr, respectively, based on release spanning 72 hr. Application of 1.6% bupivacaine-Lipospheres increased withdraw latency 25-250% but for only a 24 hr duration; b) Similarly, vocalization threshold to hind paw stimulation was increased 25-50% for 72 hr following application of 3.6% bupivacaine-Lipospheres; c) Finally, sensory blockade outlasted or equaled corresponding motor block duration for all Liposphere drug dosages. CONCLUSIONS: Liposphere delivery of local anesthetic drugs may be well suited for site-specific pharmacotherapy of neural tissue to produce SLAB. Dose-dependent effects in duration of action may include lipophilic tissue storage.

Anesthetics, Local↗