Pulsed Delivery Research Articles

Microwave Synthesis of Zeolites: Effect of Power Delivery

The effect of microwave power magnitude and pulsing frequency on the synthesis enhancement of zeolites, silicoaluminophosphate SAPO-11, silicalite, and NaY, was studied. Pulsing the microwave power compared to continuous delivery at the same averaged fed microwave power showed no effect on the nucleation and crystallization rates of SAPO-11, silicalite, or NaY. However, SAPO-11 synthesized with continuous microwave power delivery produced larger particles compared to pulsed microwave power with the same reaction time (3.77 microm for continuous versus 2.49 microm for pulsed 1 s on; 3 s off). Further, pulsed microwave power delivery used lower steady state power to maintain the same reaction temperature compared to continuous power delivery (55 W compared to 65 W, respectively). The microwave power used to heat the reaction precursors of SAPO-11 and silicalite was varied by applying cooling gas at various rates while maintaining the reaction temperatures. Significant enhancement of the crystallization rate for SAPO-11 was observed with increasing the fed microwave power (0.014 min(-1) at 65 W, 0.030 min(-1) at 130 W, and 0.066 min(-1) at 210 W), with little effect on the nucleation time. The crystallization rate to microwave power relation was found to obey a power curve (y = 0.4259x(2) - 0.2776x + 0.8517). Lower microwave power produced larger crystals but required longer reaction time to complete crystallization (3.77 microm at 65 W compared to 2.04 microm at 210 W). Conversely, silicalite synthesis at 150 degrees C was found to be independent of the magnitude of the applied microwave power.

Temperature Distributions within Zeolite Precursor Solutions in the Presence of Microwaves

While microwave enhancement of chemical syntheses has been demonstrated for a broad variety of chemical reactions, there is no accepted universal mechanism. Is the enhancement due to more efficient heating, to overheating, to nonuniform heating, or to nonthermal effects? Analyses are complicated due to the often significant spatial and temporal temperature variations in microwave reactor systems, particularly within microwave ovens. To address this, we employ multiple fiber-optic temperature probes throughout a cylindrical reactor with a focus on zeolite synthesis solutions being the dielectric medium. First, we vary the modes of power delivery (pulsed versus continuous) to quantify differences in local temperatures within a reaction vessel with water being the dielectric medium. The temperature distribution at steady state in the center of the water increased by 10 degrees C in pulsed delivery mode compared to the temperature distribution obtained in continuous delivery mode at the same average power. Then, we measured the temperature distributions for several zeolite synthesis solutions (NaY, silicalite, and SAPO-11) and water under microwave heating to investigate the temperature variations within these dielectric media. These measured temperature variations were found to be significant, depending on the dielectric permittivities of the reaction medium and their changes with temperature. Temperature profiles also depend on the microwave delivery mode and reactor configuration, i.e., the microwave reactor engineering. NaY synthesis solution exhibited the smallest penetration depth (2.6 mm at room temperature and 2.45 GHz); as a result, the solution temperature near the wall increased by 65 degrees C over the target temperature when the temperature at the center of the solution was targeted to 60 degrees C. To demonstrate the effect of overheating on zeolite synthesis, we synthesized NaY zeolite at 95 degrees C by controlling the temperature of the reaction near the wall, close to the penetration depth, and in the center away from the penetration depth. Controlling the center temperature results in greater overheating and consequently reduced nucleation time by 80 min, from 130 to 50 min.

First Experiences for Pulmonary Vein Isolation with the High‐Density Mesh Ablator (HDMA): A Novel Mesh Electrode Catheter for Both Mapping and Radiofrequency Delivery in a Single Unit

Interventional therapy of atrial fibrillation (AF) is often associated with long examination and fluoroscopy times. The use of mapping catheters in addition to the ablation catheter requires multiple transseptal sheaths for left atrial access. The purpose of this prospective study was to evaluate feasibility and safety of pulmonary vein (PV) isolation using the high-density mesh ablator (HDMA), a novel single, expandable electrode catheter for both mapping and radiofrequency (RF) delivery at the left atrium/PV junctions. Twenty-six patients with highly symptomatic paroxysmal AF (14, 53.8%) and persistent AF (12, 46.2%) were studied. Segmental PV isolation via the HDMA was performed using a customized pulsed RF energy delivery program (target temperature 55-60 degrees C, power 70-100 W, 600-900 seconds RF application time/PV). All 104 PVs in 26 patients could be ablated by the HDMA. Segmental PV isolation was achieved with a mean of 3.25 +/- 1.4 RF applications for a mean of 603 +/- 185 seconds. Entrance conduction block was obtained in 94.2% of all PV. The mean total procedure and fluoroscopy time was 159.0 +/- 32 minutes and 33.5 +/- 8.6 minutes, respectively. None of the patients experienced severe acute complications. After 3 months no PV stenosis was observed, and 85.6% and 41.6% of the patients with PAF and persistent AF, respectively, did not report symptomatic AF. In this first study of PV isolation using the HDMA, our findings suggest that this method is safe and yields good primary success rates. The HDMA simplifies AF ablation, favorably impacting procedure and fluoroscopy times.

Bulk-quantity synthesis and electrical properties of SnO 2 nanowires prepared by pulsed delivery

Tin dioxide nanowires have been realized via pulsed laser deposition techniques based on a sintered cassiterite SnO 2 target, being deposited on Si (1 0 0) substrates at room temperature. X-ray diffraction indicated that the nanowires show the tetragonal rutile structure in the form of SnO 2. Transmission electron microscopy revealed that the nanowires are structurally perfect and uniform, and diameters range from 10 nm to 30 nm, and lengths of several hundreds nanometers to a few micrometers. Selected area electron diffraction and high-resolution transmission electron microscopy verified that the nanowires grow along the [1 1 0] growth direction. Electric properties were investigated by connecting a single SnO 2 nanowire in field-effect transistor configuration. The SnO 2 nanowires based on field-effect transistor devices exhibited that the SnO 2 nanowires prepared by our method hold better electrical properties.

Effect of Pulsed or Continuous Delivery of Salt on Sensory Perception Over Short Time Intervals

Salt in the human diet is a major risk factor for hypertension and many countries have set targets to reduce salt consumption. Technological solutions are being sought to lower the salt content of processed foods without altering their taste. In this study, the approach was to deliver salt solutions in pulses of different concentrations to determine whether a pulsed delivery profile affected sensory perception of salt. Nine different salt profiles were delivered by a Dynataste device and a trained panel assessed their saltiness using time–intensity and single-score sensory techniques. The profile duration (15 s) was designed to match eating conditions and the effects of intensity and duration of the pulses on sensory perception were investigated. Sensory results from the profiles delivered in either water or in a bouillon base were not statistically different. Maximum perceived salt intensities and the area under the time–intensity curves correlated well with the overall perceived saltiness intensity despite the stimulus being delivered as several pulses. The overall saltiness scores for profiles delivering the same overall amount of sodium were statistically not different from one another suggesting that, in this system, pulsed delivery did not enhance salt perception but the overall amount of salt delivered in each profile did affect sensory perception.

In vivo effects of low level laser therapy on inducible nitric oxide synthase

Low level laser therapy (LLLT) has been demonstrated to modulate inflammatory processes with evidence suggesting that treatment protocol, such as wavelength, total energy, and number of treatments determine the clinical efficacy. In this study, the effects of LLLT mediated by different wavelengths and continuous versus pulsed delivery mode were quantified in a transgenic murine model with the luciferase gene under control of the inducible nitric oxide synthase (iNOS) expression. LLLT modulated iNOS gene expressed in the acute Zymosan-induced inflammation model is quantified using transgenic mice (FVB/N-Tg(iNOS-luc)). Here an energy density of 5 J cm(-2) at either 635, 660, 690, and 905 nm in continuous wave mode and at 905 nm for short pulse delivery were evaluated. Age of the animals was determined as additional modulating the inflammatory response and the LLLT efficacy for some treatment protocols. Animals younger than 15 weeks showed mostly reduction of iNOS expression, while older animals showed increased iNOS expression for some LLLT protocols. Intensity and time course of inducible nitric oxide expression was found to not only depend on wavelength, but also on the mode of delivery, continuous, or pulsed irradiation. LLLT exhibit different effects in induced inflammatory process according to different wavelengths and wave mode. Upregulation of iNOS gene following 905 nm pulsed wave suggests a different mechanism in activating the inflammatory pathway response when compared to the continuous wave.

Pulsing influences photoradiation outcomes in cell culture

Skin pigmentation can adversely affect phototherapy outcomes. Delivering pulsed light has been suggested as a means of enhancing efficacy. Suitable pulse frequencies remain indeterminate, often being selected empirically. This study was undertaken to determine whether pulsed light delivery mitigates the filtering effect of melanin pigment on photomodulation in vitro. Human HEP-2 cells were cultured in complete DMEM media. Photoradiation was delivered through 0.025% melanin filters at 670 nm (5.0 J/cm(2)/treatment/24 hours) for 72 hours at different pulse rates. Group A received no light treatment. Group B received treatments without pulsing. Groups C, D, E, F, and G received treatments at 6, 18, 36, 100, and 600 Hz. Cell proliferation was assessed by MTT assay and oxidative burst was measured using the 2.7 dichloro-fluorescein-diacetate assay. Cell proliferation was maximally stimulated at 100 Hz at 48 and 72 hours (n = 4, P< or =0.05). Oxidative burst was maximally stimulated at 600 Hz (n = 4, P< or =0.05). All frequencies were stimulatory at 48 and 72 hours (n = 4, P< or =0.05). This investigation suggests that light pulsing may improve outcomes by mitigating the filtration effects of cutaneous melanin. Further studies to further define these effects are warranted.

Abstract 4109: First experiences for Pulmonary Vein Isolation with the High Density Mesh Ablator

Interventional therapy of atrial fibrillation (AF) still is a complex procedure often associated with long examination- and fluoroscopy times. The use of mapping catheters in addition to the ablation catheter requires multiple transseptal sheats for left atrial access. The purpose of this prospective study was to evaluate feasibility and safety of pulmonary vein (PV) isolation using the high density mesh ablator (HDMA), a novel single, expandable electrode catheter for both mapping and radiofrequency (RF) delivery at the left atrium/PV junctions. 26 patients (PTS) with highly symptomatic paroxysmal AF (14, 53.8%) and persistent AF (12, 46.2%) were studied. Segmental PV isolation via the HDMA was performed using a customized pulsed RF energy delivery program (target temperature 55– 60 degrees, power 70 –100 Watt, 600 –900 seconds RFapplication time/PV). All 104 PV in 26 PTS could successfully be ablated by the HDMA. Segmental PV isolation was achieved with a mean of 3.25±1.4 RF applications for a mean of 603±185 sec. Entrance conduction block was obtained in &gt;94% of all PV. Mean total procedure and fluoroscopy time was 159.0±32 min and 33.5±8.6 min respectively. None of the PTS experienced severe complications. In this first study of PV isolation using the HDMA, our findings suggest that this method is safe and yields good primary success rates. Anatomical orientation and signal quality were good, allowing for excellent electrophysiological control. The HDMA simplifies the complex procedure of AF ablation, favorably impacting procedure and fluoroscopy times. Further studies are required to assess the long-term outcome.

Characterization and Application of Controllable Local Chemical Changes Produced by Reagent Delivery from a Nanopipet

We introduce a versatile method that allows local and repeatable delivery (or depletion) of any water-soluble reagent from a nanopipet in ionic solution to make localized controlled changes in reagent concentration at a surface. In this work, Na(+) or OH(-) ions were dosed from the pipet using pulsed voltage-driven delivery. Total internal reflection fluorescence from CoroNa Green dye in the bath for Na(+) ions or fluorescein in the bath for pH quantified the resulting changes in local surface concentration. These changes had a time response as short as 10 ms and a radius of 1-30 microm and depended on the diameter of the pipet used, the applied voltage, and the pipet-surface separation. After the pipet dosing was characterized in detail, two proof-of-concept experiments on single cells and single molecules were then performed. We demonstrated local control of the sodium-sensitive flagellar motor in single Escherichia coli chimera on the time scale of 1 s by dosing sodium and monitoring the rotation of a 1 microm diameter bead fixed to the flagellum. We also demonstrated triggered single-molecule unfolding by dosing acid from the pipet to locally melt individual molecules of duplex DNA, as observed using fluorescent resonance energy transfer.

The best of both worlds – A novel approach to macromolecular STM studies

The advent of scanning tunnelling microscopy (STM) and its younger sibling atomic force microscopy (AFM) have fundamentally changed the way we investigate phenomena on the molecular scale. Direct visualisation is routine and atomic and molecular level imaging is an expectation of most researchers, if not their supervisors. It might therefore be surprising to learn that whole classes of systems cannot be readily visualised using either technique. AFM is in principle the more versatile technique and ultrahigh vacuum (UHV) studies have demonstrated atomic resolution on surfaces [1] and more recently an ability to distinguish between different surface atoms [2]. However, without significant advances in force sensor technology [3] the prospect for routine molecular (not to mention sub-molecular) imaging is poor. STM, the elder sibling, is itself not without limitations. Apart from the obvious requirement of conducting substrates, it is also important to minimise resolution loss due to unwanted mixing between molecular and substrate electronic levels. In the quest to image large molecular and polymer systems using STM most researchers are faced with deciding between an ambient or UHV approach, including the oftentimes difficult task of developing appropriate sample handling and preparation procedures. Ambient STM studies typically employ gold or graphite substrates and for which samples are typically deposited directly from solution. This approach works well for a broad range of soluble molecular and polymer systems but imaging is often unstable and contamination and artefacts can be problematic [4]. The alternative UHV approach offers more stable tunnelling conditions, together with an atomically clean substrate lattice that provides an in-situ reference for structure analysis. The latter approach, however, is not amenable to systems with ultra-low vapour pressures or which decompose or denature at elevated preparation temperatures. On page XXX of this issue Laracuente and co-workers [5] describe an innovative approach to this problem that combines the best of UHV STM imaging with solution-based sample processing. Starting from a UHV prepared Si(100) surface, the authors formed a passivated H-termination by exposure to atomic hydrogen [6]. H-terminated Si(100) surfaces are stable, exceptionally well ordered and are routinely imaged with atomic resolution [7]. Transferring the H-terminated Si(100) substrate to a nitrogen-purged load-lock, samples were then drop-cast from solution onto the surface, and quickly transferred back to the STM for analysis. CDCl3 was found to be the most suitable solvent for their particular system (a pentiptycene-based polymer) and was chosen following a careful study of the contamination and oxidation levels on the H-terminated Si(100) surface after treatment with different solvents [5]. The beauty of this approach is that it overcomes the vexing problem of sample deposition by eliminating the need for Knudsen cells or even more sophisticated pulsed valve delivery systems, while at the same time provides the full benefits of

Novel Hydrogels for Rhythmic Pulsatile Drug Delivery

AbstractSummary: We are investigating an autonomous glucose‐driven hydrogel/enzyme‐based device prototype for rhythmic, pulsed delivery of gonadotropin releasing hormone (GnRH). The device employs a pH‐sensitive hydrogel membrane in conjunction with the enzyme glucose oxidase. This system delivers GnRH in rhythmic pulses when exposed to a constant level of glucose. These pulses result from autonomous pH oscillations inside the device that are created by an unstable nonlinear feedback between hydrogel permeability to glucose and production of acid by glucose oxidase. Previous versions of this prototype utilized p(N‐isopropylacrylamide‐co‐methylacrylic acid) p(NIPA‐co‐MAA) hydrogels, with 10 mol% MAA incorporated. With this membrane, which undergoes a volume transition (VT) near pH 5, pH oscillations centered around pH 5 are observed. This range is too low to sustain oscillations in physiologically buffered media. To shift the operating pH of oscillations closer to physiologic pH, we have sought ways to increase the pH of the volume transition. In this study we show that increasing the side chain length of the α‐alkylacrylic acid (RAA) comonomer enhances the overall hydrophobicity of the copolymer, and shifts the VT pH closer to physiological pH values. We also demonstrate the ability of such membranes to affect an alkaline shift in the range of oscillations in the prototype oscillator device.

The Impact of H2 Addition on Dechlorinating Microbial Communities

ABSTRACT Laboratory-scale column experiments were performed to investigate the effects of membrane-supplied H2 on tetrachloroethene (PCE) dechlorination and microbial community composition. Columns were filled with aquifer material from one of two TCE-contaminated sites and fed a PCE-spiked anaerobic minimal medium for approximately 1 year. For each experiment, one or more experimental columns were supplied with H2 via gas-permeable hollow-fiber membranes with one control column not receiving any H2. After approximately 1 year of operation, aquifer material samples were collected along the length of the columns. Bacterial communities in the samples were analyzed by amplifying the highly variable V3 region of the 16S rRNA gene and separating amplicons using denaturing gradient gel electrophoresis. Microbial community profiles in H2-fed (continuous or pulsed delivery) columns were compared with those in untreated control columns and microbial community profiles were also compared with dechlorination profiles. Selected bands were sequenced for identification. Supply of the simple electron donor H2, changed the microbial community composition, but did not decrease overall diversity. Continuous H2 addition via hollow-fiber membranes enriched for Dehalococcoides-like species, whose relative abundance correlated with enhanced dechlorination activity. PCE was completely dechlorinated to ethene in columns packed with aquifer material from Cape Canaveral, Florida; PCE was dechlorinated to only cis-dichloroethene, however, in columns packed with aquifer material from a TCE-contaminated wetland near Minneapolis, Minnesota. Unexpectedly, Dehalococcoides-like populations were detected in samples from both sets of column experiments. These results suggest that the mere detection of Dehalococcoides-like species in a sample of aquifer material is not a sufficient indicator of the potential to dechlorinate PCE to ethene via biostimulation by H2.

Preparation of fast response superabsorbent hydrogels by radiation polymerization and crosslinking of N-isopropylacrylamide in solution

Macroporous temperature-responsive poly( N-isopropylacrylamide) (PNIPAAm) hydrogels with high equilibrium swelling and fast response rates were obtained by a 60Co γ- and electron beam (EB) irradiation of aqueous N-isopropylacrylamide (NIPAAm) monomer solutions. The effect of irradiation temperatures, the dose, the addition of a pore-forming agent on the swelling ratio, and the kinetics of swelling and shrinking of the PNIPAAm gels was studied. The gels synthesized above the LCST exhibited the highest equilibrium swelling (300–400) and fastest response rate measured by minutes. Scanning electron microscope (SEM) pictures revealed that the gels synthesized above the LCST have larger pores than those prepared at temperatures below the LCST. The gels showed a reversible response to cyclical changes in temperature and might be used in a pulsed drug delivery device. The gels synthesized above the LCST exhibited the highest testosterone propionate release.

Interstitial Photodynamic Therapy of the Canine Prostate Using Intra-Arterial Administration of Photosensitizer and Computerized Pulsed Light Delivery

We determined the feasibility of complete treatment of the canine prostate and long-term effectiveness of interstitial photodynamic therapy using the intra-arterial photosensitizer QLT0074 (benzoporphyrin derivative 1,3-diene C,D-diethylene glycol ester A ring) (QLT, Vancouver, British Columbia, Canada) administration and pulsed light delivery. The prostate gland of 11 dogs were infused with QLT0074 via the prostatovesical arteries (2 mg drug per artery bilaterally) under fluoroscopic guidance. Immediately following infusion the prostate was surgically exposed and 7 optical fibers with 1.5 cm cylindrical diffusers in after loading sheaths were inserted into the prostate through a template. Light was delivered sequentially to the optic fibers via a computer driven switch system. One dog was sacrificed 6 days after photodynamic therapy to assess acute tissue effects. The other 10 dogs were monitored for clinical tolerance and urinary function, and sacrificed at between 3 and 11 months. Prostate specimens were examined microscopically to evaluate long-term tissue reactions. Comprehensive destruction of the prostate was noted in the acute dog. Except for urinary retention and mild hematuria no other perioperative complications were observed in the chronic dogs. Urodynamic examination did not reveal deleterious bladder and urethral function. Average prostate volume decreased 71% at 3 months and 56% after 6 months (p=0.007 and 0.014, respectively). Microscopic evaluation revealed prostate glandular epithelial atrophy, stromal fibrosis and mononuclear cell infiltration. Interstitial photodynamic therapy using intra-arterial QLT0074 and pulsed light delivery is safe and feasible for comprehensive destruction of the canine prostate. Clinical trials are required to confirm it for managing prostate diseases.

Pulsed mode versus near-continuous mode delivery of diode laser photocoagulation for high-risk retinopathy of prematurity

To compare structural and functional outcomes and efficiency of diode laser photocoagulation for retinopathy of prematurity (ROP) when delivered in a pulsed mode versus a near-continuous mode. A retrospective study was conducted of 138 patients who underwent diode laser photocoagulation for threshold ROP using either pulsed or near-continuous delivery. Laser-related complications and structural and functional outcomes were analyzed. Prospectively, time efficiency and total energy used were evaluated in nine infants with bilateral symmetric high-risk prethreshold ROP in which one eye of each infant was randomized to pulsed and the fellow eye to near-continuous delivery. There was no significant difference between groups with regards to prevalence of posterior disease (Zone 1 or posterior Zone 2) (p = 0.11), postoperative vitreous haze (p = 0.60), postoperative complications (p = 0.38), retinal detachment (p = 0.90), strabismus (p = 0.73), amblyopia (p = 0.69), or refractive error (p = 0.95). Mean time for treatment was 23 minutes using pulsed delivery versus 14 minutes per eye with near-continuous delivery (p < 0.001). The mean total power used per eye with pulsed mode delivery was 1.5 x 10(5) W versus 1.1 x 10(5) W with near-continuous delivery (p = 0.015). No differences in complications, functional outcome, or structural outcome were found between using pulsed mode and near-continuous mode diode laser delivery for high-risk ROP. Near-continuous laser delivery, in our hands, was more time-efficient and used less total power.

Stimuli-induced Pulsatile or Triggered Release Delivery Systems for Bioactive Compounds

As is frequently found in the living body, many vital functions are regulated by pulsed or triggered release of bioactive substances at a specific site and time. Thus it is important to develop new drug delivery devices to achieve pulsed delivery of a certain amount of drugs in order to mimic the function of the living systems to minimize the undesired side effects. The pulsed or triggered delivery systems are designed to alter their rate of drug delivery in response to stimuli such as changes in a specific molecule, a magnetic or electric field, temperature, light or mechanical forces. Such systems are suitable for the release of therapeutics that benefit from non-constant plasma concentrations. In this article, several types of drug delivery systems which cause the pulsed or triggered release of bioactive compounds due to certain external stimuli, mostly focuses on thermally-, electrically- and magnetically- induced release are described in detail. The recent patents on various delivery systems which release the active compounds only with the external stimuli are described in detail. Keywords: Pulsatile release, triggered release, bioactive compounds, reservoir devices, thermo-responsive, electro-responsive

Time-Controlled Pulsatile Delivery Systems for Bioactive Compounds

In the body under physiological conditions, many vital functions are regulated by pulsed or transient release of bioactive substances at a specific time and site. Thus, to mimic the function of living systems, it is important to develop new drug delivery devices to achieve pulsed delivery of a certain amount of a bioactive compound at predetermined time intervals. The ability to deliver bioactive compounds and/or therapeutic agents to a patient in a pulsatile or staggered release profile has been a major goal in drug delivery research over the last two decades. The plasma peak is obtained at an optimal time by timing the drug administration. The number of doses per day can be reduced. Based on the relevance of potential therapeutic applications, a variety of design strategies have been formulated in the pursuit of pulsatile release. Overall, these systems can be categorized into reservoir, capsular and osmotic devices. In this review article, several types of dosage forms, including microparticles, coarse particulates, large solid implants, hydrogels, osmotic pumps and liposomes, for time-controlled pulsatile release are discussed. This review describes the recent patents related to pre-programmed delivery systems, such as systems with eroding, soluble or rupturable barrier coatings, and systems with capsular structures.

Self‐Rupturing and Hollow Microcapsules Prepared from Bio‐polyelectrolyte‐Coated Microgels

AbstractThis paper reports on microcapsules obtained by layer‐by‐layer deposition of bio‐polyelectrolyte multilayers at the surface of biodegradable dextran microgels. The behavior of the layer‐by‐layer coating upon degradation of the microgel core strongly depends on the bio‐polyelectrolytes used. Two types of microcapsules, “self‐rupturing” microcapsules and “hollow” microcapsules, are presented. Self‐rupturing microcapsules are obtained when the swelling pressure of the degrading microgel core is strong enough to rupture the surrounding bio‐polyelectrolyte membrane. Self‐rupturing microcapsules could be of interest as a pulsed drug delivery system. Hollow microcapsules are obtained after applying multiple layers of bio‐polyelectrolyte that can withstand the swelling pressure of the degrading microgel core. Biomacromolecules (such as albumin and dextran) spontaneously accumulate in the hollow microcapsules prepared from dex‐HEMA microgels, which could be of interest for drug‐encapsulation purposes.

Comparison between pulsed and continuous radiofrequency delivery

Potentials arising in the pulmonary veins (PV) have been proposed to be a trigger of atrial fibrillation. Percutaneously, the best results for curative treatment of atrial fibrillation have been achieved by segmental or circumferential isolation of the PV. The purpose of our study was to determine the feasibility of ostial pulmonary vein isolation and to compare continuous radiofrequency (RF) with pulsed RF concerning homogeneity and transmurality of produced lesions. In vivo tests were performed in seven anesthetized and ventilated pigs. Under fluoroscopy and guided by intracardiac electrograms each of the 28 pulmonary veins was targeted for circumferential isolation near its ostium. After the continuous energy application in one PV-ostium the catheter was placed into the next PV-ostium and the same procedure was repeated using pulsed energy. The ablations were performed with an octapolar circumferential ablation catheter, with either continuous RF energy delivery to each electrode for 120 s or pulsed energy delivery to four electrodes simultaneously with a 5 ms duty cycle. Lesion diameter was measured with a microcaliper and homogeneity classified from 1 (highest) to 4 (least). More homogeneous lesions were produced in significantly less time with pulsed rather than with continuous energy delivery. There were no significant differences in impedance or temperature of the electrodes. We did not observe tissue carbonization or "popping," pulmonary vein stenosis, pericardial effusion/perforation at any time. Ostial ablation of the PV with pulsed energy delivery proved feasible. It was the faster and more reliable method of creating linear circumferential lesions with a maximum amount of homogeneity and transmurality. We observed no elevated risk of PV stenosis during our experiments.

On the possible increase in local tumour control probability for gliomas exhibiting low dose hyper-radiosensitivity using a pulsed schedule

Using modelling, we have developed a treatment strategy for gliomas exhibiting low dose hyper-radiosensitivity (HRS) that employs both a reduced dose-rate and pulsed treatment dose delivery. The model exploits the low dose hypersensitivity observed in some glioma cell lines at low radiation doses. We show, based on in vitro data, that a pulsed delivery of external beam radiation therapy could yield significant increases in local control. We therefore propose a pulsed delivery scheme for the treatment of gliomas in which the daily treatment fraction is delivered using 0.20 Gy pulses, separated by three minutes for a time-averaged dose-rate of 0.0667 Gy/min. The dose per pulse of 0.2 Gy is near or below the transition dose observed in vitro for four of the five glioma cell lines we have studied. Using five established glioma cell lines our modelling demonstrates that our pulsed delivery scheme yields a substantial increase in tumour control probability (TCP).