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Biomedical subjects

Richard Gilbert

Publications and source records attributed to Richard Gilbert.

15 recordsLinked to original sources
PubMed2006

Electric field mediated DNA motion model.

Understanding the motion and the governing equations of a molecule's path in tissue is an ultimate requirement for the repeatable, site specific delivery of molecules [Joseph D. Hickey. Modelling the Motion of Ions and Molecules in Electroporation and Electrophoresis Field Conditions. University of South Florida, College of Arts and Sciences, Department of Physics, Tampa, Florida, 2003., Joseph D. Hickey and Richard Gilbert. Modeling the electromobility of ions in a target tissue. DNA and Cell Biology, 22 (12) (2003) 823-828.]. This paper describes a computationally efficient mathematical model and simulation technique for the examination of DNA fragments in a 1% agarose gel. The speed of the individual DNA fragments through the agarose gel was described through two parts. The maximum velocity was calculated using the Coulombic force divided by Stoke's law and that value was retarded by an exponential rate equation. The simulation utilizes previously published techniques modified for this specific application [Joseph D. Hickey and Richard Gilbert. Fluid flow electrophoresis model. Bioelectrochemistry, 63 (2) (2004) 365-367., Joseph D. Hickey and Richard Gilbert. Modeling the electromobility of ions in a target tissue. DNA and Cell Biology, 22 (12) (2003) 823-828.]. Five representative DNA fragment sizes that span the resolution of a 1% agarose gel were chosen for this analysis. The speeds corresponding to these five DNA fragment sizes were converted into discrete values and used in a 50 step simulation. The resultant error comparing the simulation with experimental distance was 7.76%. Through a 1-D optimization procedure, this error was reduced to 3.02% for a 52 step simulation.

Algorithms↗
PubMed2006

Comparison of 2-dimensional and 3-dimensional acquisition for 18F-FDG PET oncology studies performed on an LSO-based scanner.

UNLABELLED: Three-dimensional (3D) PET acquisition has the potential to reduce image noise but the advantage of 3D PET for studies outside the brain has not been well established. To compare the performance of 2-dimensional (2D) and 3D acquisition for whole-body (18)F-FDG applications, a series of patient studies were performed using a lutetium oxyorthosilicate (LSO)-based tomograph. METHODS: Comparative 2D and 3D images were acquired for 27 oncology patients using an LSO-based tomograph. Data acquisition (350-650 keV, 6 ns) started 99 +/- 12 min (mean +/- SD) after injection of 624 +/- 76 MBq (18)F-FDG. Bias caused by tracer redistribution and decay was eliminated by acquiring dynamic data over a single-bed position using a protocol that alternated between septa-in and septa-out modes (2D, 3D, 2D, 3D, 2D, 3D). Frames were combined to form 8 statistically independent sinograms: four 2D replicates (105 s) and four 3D replicates (90 s). The different frame durations in 2D and 3D compensated for the different number of overlapping bed positions required for an 85-cm whole-body study. Images were reconstructed with either 2D or fully 3D ordered-subsets expectation maximization (2 iterations and 8 subsets; 2D 6-mm gaussian, 3D 5- and 6-mm gaussian). Image target-to-background ratio was assessed by dividing the lesion maximum by the mean within a neighboring background region. Image noise was assessed by applying background regions of interest to the replicate images and calculating the within-patient coefficient of variation. RESULTS: The difference in target-to-background ratio between the 2D and 3D images, when they were filtered with 6-mm and 5-mm gaussian filters, respectively, was not highly statistically significant (P = 0.16). The mean ratio of 3D to 2D image values was 0.94 with 95% limits of agreement of 0.63-1.41. The within-patient coefficients of variation for the 2D and 3D images were 13% +/- 15% and 9% +/- 10%, respectively (P = 0.0005). CONCLUSION: Under conditions of matched target to-to-background ratios, the 3D mode was found to produce images with significantly less variability than the 2D mode. These data provide support for the use of 3D acquisition with LSO detectors to reduce scan times in whole-body (18)F-FDG applications.

Equipment Design↗
PubMed2005

The proportion of general practitioner referrals to a hospital Respiratory Medicine clinic suitable to be seen in a GPwSI Respiratory Clinic.

AIMS: The purpose of this study was to examine the proportion of general practitioner (GP) referrals to a hospital Respiratory Medicine clinic which might be suitable for a General Practitioner with a Special Interest (GPwSI) Respiratory Clinic. METHOD: All GP referral letters to the Respiratory Medicine Department of a teaching hospital, apart from urgent cancer referrals, were identified from two two-week periods. All patient and practice identifications were removed. Two GPs and one Consultant Respiratory Physician assessed each of the anonymised referral letters to determine the patient's suitability to be seen in a GPwSI Respiratory Clinic, assuming such a clinic had a predetermined range of investigative facilities. RESULTS: Out of 96 referrals covering a wide range of respiratory conditions apart from lung cancer, 22 (23%) were considered by all assessors to be suitable for a GPwSI clinic, and there was full agreement that 40 referrals (42%) were unsuitable. The other 34 referrals (35%) had varying degrees of agreement on suitability. The largest groups of patient referrals considered suitable for a GPwSI clinic were those with chronic obstructive pulmonary disease (COPD) or cough as the main presenting clinical problem. The commonest groups considered unsuitable were referrals of patients with an abnormal chest radiograph, haemoptysis, or possible interstitial lung disease. CONCLUSION: This small study has shown that at least a fifth of GP referrals to a hospital Respiratory Medicine clinic could be seen in a suitably resourced GPwSI clinic, with consequent reductions in hospital outpatient waiting lists and improved accessibility for patients. This finding will be of interest to potential commissioners of GPwSI services especially with the advent of Practice-based Commissioning.

Journal Article↗
PubMed2005

Development of an integrated microfluidic platform for dynamic oxygen sensing and delivery in a flowing medium.

This paper describes a platform for real-time sensing of dissolved oxygen in a flowing microfluidic environment using an oxygen-sensitive luminescent dye (platinum octaethylporphyrin ketone) integrated into a micro-oxygenator device. Using a phase-based detection method, the luminescent decay lifetime of the dye was consistent with the linear Stern-Volmer relationship using both gaseous and aqueous samples. Maximum sensor resolution varied between 120-780 ppb across a range of dissolved oxygen (DO) concentrations ranging from 0-42.5 ppm. The sensor was subsequently used to determine the convective mass-transfer characteristics of a multi-layer polydimethylsiloxane (PDMS) microfluidic oxygenator. The membrane-based oxygenator showed excellent agreement with an analytical convection model, and the integrated oxygen sensor was accurate across a wide range of tested flow rates (0.05-5 mL min(-1)). The device is unique for its ease of fabrication and highly flexible configuration, as well as the novel incorporation of oxygen delivery and detection in a single micro-device. Potential applications include tissue engineering, cell culturing, and miniaturized bio-assays that require the delivery and/or detection of precise quantities of oxygen within a microfluidic construct.

Biological Assay↗
PubMed2004

Fluid flow electrophoresis model.

Molecular delivery via electroporation is typically done via molecular diffusion and tissue perfusion. The inherent variability in those distribution methods limits the efficacy of this medical and laboratory technique. Electrophoresis has been shown to improve the distribution and placement of the molecule [Gene Therapy 9 (2002) 1286]. This paper presents a fluid flow model for electrophoresis in tissues. Parallel plate and four-needle needle array electrodes are the electrodes modeled as the delivery devices. The parallel plate electrode produces a homogeneous distribution of the analyte but the needle array electrode creates a peak where the electric field effects diminish.

Animals↗
PubMed2004

New imaging techniques: integrating structural and functional imaging in the head and neck.

Traditionally, the mainstay of head and neck MR imaging has been the identification of structural alterations resulting from pathology. Now, the advent of fast MR imaging techniques provides the opportunity for radiologists to integrate structural and functional imaging in the head and neck. This article highlights functional imaging techniques that provide a means toward a complete evaluation of structural integrity and function in various systems of the head and neck.

Journal Article↗
PubMed2003

Cumulative irritancy comparison of adapalene gel 0.1% versus other retinoid products when applied in combination with topical antimicrobial agents.

This randomized, investigator-blinded study evaluated the level of skin tolerance to adapalene gel 0.1%, tretinoin cream 0.025%, or tretinoin microsphere gel 0.1% when applied in combination with clindamycin phosphate lotion 1%, erythromycin gel 2%, benzoyl peroxide gel 5%, or erythromycin-benzoyl peroxide gel. A total of 37 subjects underwent daily application of the topical antimicrobial and retinoid products to sites on their upper back under protective patches for approximately 16 hours each day; Friday patches were left in place over the weekend. Testing continued daily for 3 weeks or until discontinuation caused by a severe adverse reaction to any of the test products or to the patch. Adapalene gel 0.1% demonstrated statistically significantly (P <.001) less irritation after repeated application under occlusive conditions than tretinoin cream 0.025% or tretinoin microsphere gel 0.1%. Moreover, the application of adapalene gel 0.1% under these conditions, concomitantly with various antimicrobial agents, was safe and well tolerated in this subject population. In view of its low irritation potential and its efficacy, adapalene gel 0.1%, in combination with antimicrobial agents should be considered for the treatment of acne vulgaris.

Acne Vulgaris↗
PubMed2003

Modeling the electromobility of ions in a target tissue.

Electroporation is a clinical and laboratory technique for the delivery of molecules to cells. This method imposes electric fields onto cells or tissues through the use of electrodes and a set of electrical parameters to ultimately incorporate molecules into the cells. Clinical applications may include using directional fields to bring therapeutics to the target tissues before triggering an electroporation event. The choice of applicator may also have a significant influence on this molecular flow. Modeling ionic flow in tissues will yield insight into selecting the appropriate parameters or electroporation signature for a desired target application. In this paper, the motion of tissue injected ions was modeled for two common electroporation applicator configurations-the parallel plate, and the four needle electrodes. This electric field induced fluid flow model predicts that the parallel plate applicator ultimately directs the movement of an ionic therapeutic in a forward manner with side motion due only to obstruction, while the four-needle applicator directs anisotropic flow within the field ultimately forcing the therapeutic into a mound at the fringes of the induced electric field.

Cell Physiological Phenomena↗
PubMed2003

Cumulative irritation comparison of adapalene gel and solution with 2 tazarotene gels and 3 tretinoin formulations.

Forty-two subjects with normal skin were enrolled in a single-center study to assess the cumulative irritancy potential of adapalene (Differin gel 0.1% and Differin solution 0.1%) compared with tazarotene (Tazorac gels 0.05% and 0.1%), tretinoin (Retin-A Micro gel 0.1%, Avita cream 0.025%, and Avita gel 0.025%), and white petrolatum (negative control). All test materials were applied randomly, under occlusion, to sites located on either side of the midline--the mid thoracic area of the subjects' backs. All patches were applied daily, Monday through Friday, to the same sites, unless the degree of reaction to a test product or adhesive necessitated removal (grade 3). Thirty-eight of the 42 subjects (90.5%) completed the study. Thirty-four of those 38 subjects (89.5%) had to discontinue using both tazarotene concentrations due to intolerance. Patch discontinuations for the remaining test materials were as follows: 7 subjects discontinued use of tretinoin microsphere gel 0.1%, 3 discontinued tretinoin cream 0.025%, 1 discontinued tretinoin gel 0.025%, and 1 discontinued adapalene gel 0.1%. None of the subjects discontinued use of the white petrolatum or the adapalene solution 0.1%. Adapalene gel and solution 0.1% were statistically (P<.01) less irritating than both tazarotene gels 0.1% and 0.05%, tretinoin microsphere gel 0.1%, and tretinoin gel 0.025%, and they were not statistically different from tretinoin gel 0.025%.

Adapalene↗
PubMed2003

Cumulative irritancy potential of adapalene cream 0.1% compared with adapalene gel 0.1% and several tretinoin formulations.

Thirty-one subjects (8 males and 23 females; mean age, 49.8 years) were enrolled in a single-center study to assess the irritancy potential of adapalene (Differin cream 0.1% and Differin gel 0.1%) and tretinoin (Avita cream 0.025%, Retin-A cream 0.025%, Retin-A cream 0.05%, Retin-A Micro gel 0.1%, and generic cream 0.025%) as compared with white petrolatum when applied under occlusive conditions. All test materials were applied randomly under occlusion to sites located on the upper area of the subject's back under protective patches. All patches were applied to the same sites unless the degree of reaction to a test product or the adhesive necessitated removal (grade 3). Each test material was applied daily, Monday through Friday, for approximately 24 hours, with the Friday patches left in place over the weekend. Twenty-six of the 31 subjects (84%) completed the study. No subject discontinued because of an adverse event. Five subjects voluntarily discontinued the study early for reasons unrelated to study treatment (4 subject request and 1 lost to follow-up). In the statistical comparison of the 7 test products, the mean cumulative irritancy index of both adapalene cream 0.1% and gel 0.1% was statistically significantly (P<.05) lower than for all of the tretinoin products used and was not significantly higher than the negative control product (white petrolatum).

Adapalene↗
PubMed2002

New imaging techniques: integrating structural and functional imaging in the head and neck.

The application of fast MRI techniques provides the opportunity to image function in various systems of the head and neck. Incorporating fMRI techniques into head and neck imaging protocols provides the potential for the head and neck radiologist to investigate structural integrity and function and thus play a central role in the diagnostic and prognostic work-up of the patient.

Animals↗
PubMed2002

Electric field enhanced plasmid delivery to liver hepatocellular carcinomas.

Electric field enhanced molecular delivery for cancer research and treatment is a new technology that has demonstrated its effectiveness in clinical trials using bleomycin or cisplatin (Heller, R., Gilbert, R., Jaroszeski, M. J. Clinical applications of electrochemotherapy, Advanced Drug Delivery Reviews 35,119-129, 1999), as chemotherapeutic agents. The technology is being investigated in research applications for applicability as a method to enhance gene expression in a target tumor. Success is predicated on an appropriate effective electric field mediated delivery protocol that triggers significant appropriate gene expression duration and levels. An electric field mediated delivery protocol includes a set of conditions associated with the electric field, the electroporation signature, as well as parameters associated with the plasmid and the electric field applicator. Manipulation of the electrical parameters within the electroporation signature generates different gene expression levels in liver hepatocellular carcinomas. Statistically significant gene expression levels were obtained that differed by an order of magnitude when two different electric field strength and duration conditions were employed.

Animals↗
PubMed2002

Effect of electrochemotherapy on muscle and skin.

The efficient delivery of drugs to tumors is an important tool for the treatment of a variety of cancers. Electric pulses have been shown to facilitate the uptake of molecules through the cell membrane. This procedure has been successful in increasing the effectiveness of anti-tumor agents (electrochemotherapy; ECT). Response rates of >80% have been obtained in both animal and human trials for several types of skin malignancies. The study reported here examined the effect of ECT on normal tissue. The hind limbs of Sprague Dawley rats were treated with 1-3 electroporation sequences in the presence or absence of the drug (bleomycin) which was administered at 4, 8 or 16 units/ml. The treated sites were examined histologically 3, 14 and 56 days later. Limb function was not affected by the treatment and skin and muscle necrosis was only seen at the higher doses.

Animals↗
PubMed2002

Evolutionary computational methods to predict oral bioavailability QSPRs.

This review discusses evolutionary and adaptive methods for predicting oral bioavailability (OB) from chemical structure. Genetic Programming (GP), a specific form of evolutionary computing, is compared with some other advanced computational methods for OB prediction. The results show that classifying drugs into 'high' and 'low' OB classes on the basis of their structure alone is solvable, and initial models are already producing output that would be useful for pharmaceutical research. The results also suggest that quantitative prediction of OB will be tractable. Critical aspects of the solution will involve the use of techniques that can: (i) handle problems with a very large number of variables (high dimensionality); (ii) cope with 'noisy' data; and (iii) implement binary choices to sub-classify molecules with behavior that are qualitatively different. Detailed quantitative predictions will emerge from more refined models that are hybrids derived from mechanistic models of the biology of oral absorption and the power of advanced computing techniques to predict the behavior of the components of those models in silico.

Animals↗