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1

Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery  

SciTech Connect

Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output.

Engelsman, M.; Lu, H.-M.; Herrup, D.; Bussiere, M.; Kooy, H. M. [Department of Radiation Oncology, Francis H. Burr Proton Therapy Center, Massachusetts General Hospital, Boston, Massachusetts 02114 (United States) and Harvard Medical School, Boston, Massachusetts 02114 (United States)

2009-06-15

2

The accurate diagnosis and treatment of lipodermatosclerosis.  

PubMed

Patients attending hospital expect to receive effective evidence-based treatment that improves health and minimises the risk of harm. Clinicians working in acute hospitals are often under pressured to treat people quickly and in such circumstances, some conditions can be misdiagnosed and inappropriately treated. This article uses a case study approach to illustrate the important differences in clinical presentation and treatment of acute and chronic lipodermatosclerosis and cellulitis. It also highlights the importance of clinicians receiving ongoing education so that they can improve their knowledge and provide appropriate care for older people. The article also recommends that national guidelines are developed to enable clinicians to differentiate between infective disorders such as cellulitis and venous disorders so that patients receive prompt effective evidence-based treatment. PMID:19543156

Nazarko, Linda

3

How accurate are patients in reporting their antidepressant treatment history?  

Microsoft Academic Search

Background: A patient’s report of their antidepressant treatment history is one of the most important pieces of information used in selecting an antidepressant regimen. It is currently unknown how accurate patients are in describing and characterizing their antidepressant treatment history. Methods: Seventy-three patients receiving treatment for depression at our outpatient psychiatric practice were interviewed by an independent evaluator who was

Michael A Posternak; Mark Zimmerman

2003-01-01

4

Platelets as delivery systems for disease treatments  

PubMed Central

Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets and utilizing platelets as delivery systems for disease treatment would be a logical approach. This paper reviews the genetic therapy for inherited bleeding disorders utilizing platelets as delivery system, with a particular focus on platelet-derived FVIII for hemophilia A treatment.

Shi, Qizhen; Montgomery, Robert R.

2010-01-01

5

Towards an accurate treatment of ?? ? ? transitions: Moving onto N6.-  

NASA Astrophysics Data System (ADS)

Dimeric ?? radical anions are ubiquitous, and their formation, spectroscopy and outcome can often be elucidated by density functional theory. But for shorter interfragment distances, three-electron two-center systems can be reluctant to a single-determinant description, such as the hexanitrogen radical anion. For N6.-, we show that multireference configuration interactions calculations are required to recover its characteristic electronic excitation energy, while TDDFT fails even with modern exchange-correlation functionals. The effects of vibronic couplings on the absorption spectrum are delineated based on a full quantum mechanical dynamical treatment; this study opens the door towards an accurate description of the subtle solvatochromism of hemi-bonded systems.

Dumont, Élise; Ferré, Nicolas; Monari, Antonio

2013-08-01

6

Accurate functional volume definition in PET for radiotherapy treatment planning  

Microsoft Academic Search

Accurate volume contouring in PET is now considered crucial in radiotherapy as the use of functional imaging allows improved gross tumour volume (GTV) definition. On the other hand, an accurate delineation of the GTV as well as the definition of variable activity accumulation regions inside the tumour itself may facilitate the applications of “dose painting” for optimization of dosimetry. The

M. Hatt; A. Dekker; D. De Ruysscher; M. Oellers; P. Lambin; C. Roux; D. Visvikis

2008-01-01

7

New oral delivery systems for treatment of inflammatory bowel disease  

Microsoft Academic Search

Inflammatory bowel disease (IBD) is often localized to specific sites in the gastrointestinal tract (GIT). As a result, this disease can be treated with oral site-specific (targeted) drug delivery systems. Targeted delivery systems for treatment of IBD are designed to increase local tissue concentrations of antiinflammatory drugs from lower doses compared with systemic administration. This review addresses the impact disease

David R. Friend

2005-01-01

8

Transdermal delivery of drugs for the treatment of bone diseases  

Microsoft Academic Search

The current status of transdermal drug delivery for the treatment of bone diseases is described in this review. The structure, physiology and function of skin and their importance in determining delivery into and across skin are discussed. Special emphasis has been devoted to a description of the major pathways of transport across the skin and the quite continuing controversy over

Chandrasekharan Ramachandran; David Fleisher

2000-01-01

9

Translation research: from accurate diagnosis to appropriate treatment  

PubMed Central

This review article focuses on the various aspects of translational research, where research on human subjects can ultimately enhance the diagnosis and treatment of future patients. While we will use specific examples relating to the asbestos related cancer mesothelioma, it should be stressed that the general approach outlined throughout this review is readily applicable to other diseases with an underlying molecular basis. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, we now have the ability to identify clinically applicable "genotype"-"phenotype" associations across cohorts of patients that can rapidly be translated into useful diagnostic and treatment strategies. This review will touch on the various steps in the translational pipeline, and highlight some of the most essential elements as well as possible roadblocks that can impact success of the program. Critical issues with regard to Institutional Review Board (IRB) and Health Insurance Portability and Accountability Act (HIPAA) compliance, data standardization, sample procurement, quality control (QC), quality assurance (QA), data analysis, preclinical models and clinical trials are addressed. The various facets of the translational pipeline have been incorporated into a fully integrated computational system, appropriately named Dx2Tx. This system readily allows for the identification of new diagnostic tests, the discovery of biomarkers and drugable targets, and prediction of optimal treatments based upon the underlying molecular basis of the disease.

Webb, Craig P; Pass, Harvey I

2004-01-01

10

Gated Treatment Delivery Verification With On-Line Megavoltage Fluoroscopy  

SciTech Connect

Purpose: To develop and clinically demonstrate the use of on-line real-time megavoltage (MV) fluoroscopy for gated treatment delivery verification. Methods and Materials: Megavoltage fluoroscopy (MVF) image sequences were acquired using a flat panel equipped for MV cone-beam CT in synchrony with the respiratory signal obtained from the Anzai gating device. The MVF images can be obtained immediately before or during gated treatment delivery. A prototype software tool (named RTReg4D) was developed to register MVF images with phase-sequenced digitally reconstructed radiograph images generated from the treatment planning system based on four-dimensional CT. The image registration can be used to reposition the patient before or during treatment delivery. To demonstrate the reliability and clinical usefulness, the system was first tested using a thoracic phantom and then prospectively in actual patient treatments under an institutional review board-approved protocol. Results: The quality of the MVF images for lung tumors is adequate for image registration with phase-sequenced digitally reconstructed radiographs. The MVF was found to be useful for monitoring inter- and intrafractional variations of tumor positions. With the planning target volume contour displayed on the MVF images, the system can verify whether the moving target stays within the planning target volume margin during gated delivery. Conclusions: The use of MVF images was found to be clinically effective in detecting discrepancies in tumor location before and during respiration-gated treatment delivery. The tools and process developed can be useful for gated treatment delivery verification.

Tai An, E-mail: atai@mcw.ed [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Christensen, James D.; Gore, Elizabeth [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Khamene, Ali [Imaging and Visualization Department, Siemens AG, Princeton, NJ (United States); Boettger, Thomas [Oncology Care Systems, Siemens AG, Heidelberg (Germany); Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States)

2010-04-15

11

EVALUATION OF INTENSITY MODULATED RADIATION THERAPY (IMRT) DELIVERY ERROR DUE TO IMRT TREATMENT PLAN COMPLEXITY AND IMPROPERLY MATCHED DOSIMETRY DATA  

Microsoft Academic Search

Intensity modulated radiation therapy (IMRT) is a technique that delivers a highly conformal dose distribution to a target volume while attempting to maximally spare the surrounding normal tissues. IMRT is a common treatment modality used for treating head and neck (H&N) cancers, and the presence of many critical structures in this region requires accurate treatment delivery. The Radiological Physics Center

Jacqueline R Tonigan

2011-01-01

12

Advances in the delivery of treatments for Parkinson's disease.  

PubMed

Innovative drug delivery in Parkinson's disease (PD) has the potential to reduce or avoid many side effects of current treatment, such as wearing-off type fluctuations, dyskinesia, on-off phenomena or bouts of motor freezing. The traditional orally administered formulations of l-dihydroxyphenylalanine combined with a peripheral aromatic acid decarboxylase inhibitor remain the mainstay of treatments for PD. However, such combination therapies have been further formulated to extend their duration of action by including a catechol-O-methyltransferase inhibitor. Preventing the breakdown of dopamine has also been achieved by monoamine oxidase-B inhibition; this approach now having been formulated for sublingual use (Zelapar, Valeant Pharmaceuticals). An alternative approach bypasses the oral route of administration and instead relies on continuous duodenal infusion (Duodopa, Solvay, NeoPharma AB) for better therapeutic effect. The clinical use of dopamine agonists as antiparkinsonian drugs now incorporates a variety of delivery techniques. For example, apomorphine, which relies on parenteral administration for maximum bioavailability, may be delivered via rectal, intranasal, sublingual and subcutaneous (e.g., Apokyn, Mylan Bertek) routes. Meanwhile, rotigotine and lisuride have both been formulated for delivery via skin patches. Finally, the authors examine more experimental delivery techniques, including the delivery of genes via viral vectors or liposomes, intracranial transplant of a variety of cells and of L-dihydroxyphenylalanine by prodrug-dispensing liposomes or pulmonary delivery (AIR, Alkermes). The advent and application of these varied technologies will help encourage patient-specific means of treatment for PD. PMID:16296809

Johnston, Tom H; Fox, Susan H; Brotchie, Jonathan M

2005-11-01

13

Accurate Aerial Delivery System.  

National Technical Information Service (NTIS)

The Coast Guard, as a part of their sea rescue mission, are frequently required to aid distressed boats by dropping from an airplane a package containing emergency pumping equipment. The boats usually are unable to maneuver, making it necessary to accompl...

W. L. Black B. W. Jezek J. S. Taylor R. D. Mikesell E. A. Thomassen

1969-01-01

14

Delivery systems and cost recovery in Mectizan treatment for onchocerciasis.  

PubMed

The efficiency of on-going delivery systems and cost recovery in Mectizan (ivermectin, MSD) treatment for onchocerciasis are reviewed. The search is on for an effective system of Mectizan delivery, involving drug procurement, delivery from port to districts and distribution to eligible persons, which can be sustained by the endemic countries for many years. The mechanisms for procuring and clearing the drug at the ports, and the drug's integration into the existing delivery systems of each national health service, need to be improved. Although large-scale treatments by mobile teams or community-based methods evidently achieve high and satisfactory rates of coverage, they also incur high recurrent costs which have to be covered by external partners and are not sustainable by national health services. Cost-sharing is considered an important factor in a sustainable delivery system and community-directed treatment, in which the community shares the cost and ownership of local distribution and is empowered to design and implement it, is likely to be more cost-effective and sustainable. PMID:9861264

Amazigo, U; Noma, M; Boatin, B A; Etya'alé, D E; Sékétéli, A; Dadzie, K Y

1998-04-01

15

Substance Abuse Treatment Clinician Opinions and Infectious Disease Service Delivery  

Microsoft Academic Search

Substance abuse treatment programs are an important platform for delivery of services for infectious diseases associated with drug and alcohol use. However, important components of infectious disease care are not universally provided. Clinician training often focuses on information about infectious diseases and less attention is paid to provider opinions and attitudes that may be barriers to providing infectious diseases services.

Kathlene Tracy; Lawrence S. Brown; Steven Kritz; Donald Alderson; Jim Robinson; Edmund J. Bini; Michael Levy; Donald Calsyn; Traci Rieckmann; Bret Fuller; Pat McAuliffe; John Rotrosen

2009-01-01

16

Improved treatment of nicotine addiction and emerging pulmonary drug delivery.  

PubMed

Nicotine addiction remains the leading cause of death and disease in developed and developing nations and a major cause of mortality around the world. Currently, nicotine replacement therapies (NRTs), bupropion, and varenicline are approved by the regulatory agencies as first-line treatments for nicotine addiction. Emerging evidence indicates that varenicline and bupropion have some therapeutic limitations for treating nicotine addiction with oral route of administration. Thus, continued investigation of innovative drug delivery for nicotine addiction remains a critical priority. This review will discuss some novel strategies and future directions for pulmonary drug delivery, an emerging route of administration for smoking cessation. It is anticipated that the advancement of knowledge on pulmonary drug delivery will provide better management for nicotine addiction and other addictive disorders. PMID:22890202

Islam, Nazrul; Rahman, Shafiqur

2012-06-01

17

Drug delivery with carbon nanotubes for in vivo cancer treatment.  

PubMed

Chemically functionalized single-walled carbon nanotubes (SWNT) have shown promise in tumor-targeted accumulation in mice and exhibit biocompatibility, excretion, and little toxicity. Here, we show in vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug, to branched polyethylene glycol chains on SWNTs via a cleavable ester bond to obtain a water-soluble SWNT-PTX conjugate. SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol in a murine 4T1 breast cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention. Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses. PMID:18701489

Liu, Zhuang; Chen, Kai; Davis, Corrine; Sherlock, Sarah; Cao, Qizhen; Chen, Xiaoyuan; Dai, Hongjie

2008-08-15

18

Drug delivery options for the treatment of ocular inflammation.  

PubMed

Treatments available for ocular inflammatory diseases and their associated complications have expanded significantly over the course of the last ten years. While corticosteroids are a mainstay of therapy for uveitis and macular edema, the methods of delivering corticosteroids have evolved. Intravitreal triamcinolone acetonide provides a local therapy for persistent cystoid macular edema (CME) and posterior uveitis. Other intravitreal therapies, such as bevacizumab and methotrexate, have also been used successfully in uveitic CME. Sustained release intravitreal implants, including the fluocinolone acetonide implant and the dexamethasone drug delivery system, offer an alternative therapy for chronic, recalcitrant posterior uveitis and CME. Their design was inspired by the ganciclovir implant, which prevented the progression of CMV retinitis in AIDS patients. Technological advances in drug delivery have supplied new treatments for patients with ocular inflammatory disease. PMID:21091013

Lobo, Ann-Marie; Sobrin, Lucia; Papaliodis, George N

19

Intrauterine Drug Delivery for Contraception and Gynaecological Treatment: Novel Approaches  

Microsoft Academic Search

\\u000a This chapter describes the development of new intrauterine drug delivery products, which are designed to provide improved\\u000a methods for the prevention and treatment of gynaecological conditions, improvements to birth control methods, and higher levels\\u000a of safety, user acceptability, compliance, and quality of life for women. The development of frameless intrauterine systems\\u000a is such an attempt to improve on the performance

Dirk Wildemeersch

20

Hollow waveguide delivery system for the ophthalmology treatment  

NASA Astrophysics Data System (ADS)

For the purpose of the ophthalmology treatments a special hollow waveguide based delivery instrument was developed. It consists of a 2 m long cyclic olefin polymer coated silver hollow glass waveguide (inner diameter 700 ?m) and the special cap allowing the contact of the waveguide with the wet eye tissues. The transmission characteristics for a delivery of a mid-infrared Er:YAG radiation (2.94 ?m) was measured. Then the pre-clinical interaction experiments of the Er:YAG laser radiation with the eye tissue (cornea, lens, and sclera) were performed with this delivery instrument. A comparison of two types of interactions results - the action of Er:YAG free running - 40 ?s long pulses and giant 450 ns long pulses were made. The human eye tissues (in vitro) were cut and samples (cornea, lens, and sclera) were gradually irradiated by the mid-infrared radiation with the energy of 7 mJ (the corresponding spot size diameter was equal ~ 700 ?m). The laser energy density used in this experiment was 1.8 J/cm2. From results it can be concluded that the giant pulses are more efficient in the ablation of the cornea, they are comparable with the free-running long pulses in the case of lens grinding, and they are less functioning for the sclera perforation. As concern the hollow waveguide delivery system, it has been proved that the energy delivered by this system was sufficient and suitable in both cases Ð for delivery of long - free-running pulses, and short - giant pulses as well.

Jelinkova, Helena; Nemec, Michal; Sulc, Jan; Cech, Miroslav; Miyagi, Mitsunobu; Iwai, Katsumasa; Shi, Yi-Wei; Matsuura, Yuji; Pašta, Jiri

2003-07-01

21

Convection-enhanced delivery for the treatment of brain tumors  

PubMed Central

The brain is highly accessible for nutrients and oxygen, however delivery of drugs to malignant brain tumors is a very challenging task. Convection-enhanced delivery (CED) has been designed to overcome some of the difficulties so that pharmacological agents that would not normally cross the BBB can be used for treatment. Drugs are delivered through one to several catheters placed stereotactically directly within the tumor mass or around the tumor or the resection cavity. Several classes of drugs are amenable to this technology including standard chemotherapeutics or novel experimental targeted drugs. The first Phase III trial for CED-delivered, molecularly targeted cytotoxin in the treatment of recurrent glioblastoma multiforme has been accomplished and demonstrated objective clinical efficacy. The lessons learned from more than a decade of attempts at exploiting CED for brain cancer treatment weigh critically for its future clinical applications. The main issues center around the type of catheters used, number of catheters and their exact placement; pharmacological formulation of drugs, prescreening patients undergoing treatment and monitoring the distribution of drugs in tumors and the tumor-infiltrated brain. It is expected that optimizing CED will make this technology a permanent addition to clinical management of brain malignancies.

Debinski, Waldemar; Tatter, Stephen B

2013-01-01

22

Drug delivery with carbon nanotubes for in vivo cancer treatment  

PubMed Central

Chemically functionalized single-walled carbon nanotubes (SWNTs) have shown promise in tumor targeted accumulation in mice and exhibit biocompatibility, excretion and little toxicity. Here, we demonstrate in-vivo SWNT drug delivery for tumor suppression in mice. We conjugate paclitaxel (PTX), a widely used cancer chemotherapy drug to branched polyethylene-glycol (PEG) chains on SWNTs via a cleavable ester bond to obtain a water soluble SWNT-paclitaxel conjugate (SWNT-PTX). SWNT-PTX affords higher efficacy in suppressing tumor growth than clinical Taxol® in a murine 4T1 breast-cancer model, owing to prolonged blood circulation and 10-fold higher tumor PTX uptake by SWNT delivery likely through enhanced permeability and retention (EPR). Drug molecules carried into the reticuloendothelial system are released from SWNTs and excreted via biliary pathway without causing obvious toxic effects to normal organs. Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses.

Liu, Zhuang; Chen, Kai; Davis, Corrine; Sherlock, Sarah; Cao, Qizhen; Chen, Xiaoyuan; Dai, Hongjie

2008-01-01

23

Sustained Release Intraocular Drug Delivery Devices for Treatment of Uveitis  

PubMed Central

Corticosteroids have been the mainstay of uveitis therapy. When intraocular inflammation is unresponsive to steroids, or steroid related side effects become a concern, steroid-sparing medications may be administered which can be classified into immunosuppressive and immunomodulatory agents. Uveitis treatment can be delivered systemically, topically, periocularly or intraocularly. All of the above mentioned medications can entail significant systemic side effects, particularly if administered for prolonged durations, which may become treatment-limiting. Some medications, particularly hydrophobic compounds, may poorly cross the blood–retinal barrier. Topical medications, which have the least side effects, do not penetrate well into the posterior segment and are unsuitable for posterior uveitis which is often sight-threatening. Intraocular or periocular injections can deliver relatively high doses of drug to the eye with few or no systemic side effects. However, such injections are associated with significant complications and must often be repeated at regular intervals. Compliance with any form of regular medication can be a problem, particularly if its administration is associated with discomfort or if side effects are unpleasant. To overcome the above-mentioned limitations, an increasing number of sustained-release drug delivery devices using different mechanisms and containing a variety of agents have been developed to treat uveitis. This review discusses various current and future sustained-release ophthalmic drug delivery systems for treatment of uveitis.

Haghjou, Nahid; Soheilian, Masoud; Abdekhodaie, Mohammad Jafar

2011-01-01

24

Can radiation therapy treatment planning system accurately predict surface doses in postmastectomy radiation therapy patients?  

SciTech Connect

Skin doses have been an important factor in the dose prescription for breast radiotherapy. Recent advances in radiotherapy treatment techniques, such as intensity-modulated radiation therapy (IMRT) and new treatment schemes such as hypofractionated breast therapy have made the precise determination of the surface dose necessary. Detailed information of the dose at various depths of the skin is also critical in designing new treatment strategies. The purpose of this work was to assess the accuracy of surface dose calculation by a clinically used treatment planning system and those measured by thermoluminescence dosimeters (TLDs) in a customized chest wall phantom. This study involved the construction of a chest wall phantom for skin dose assessment. Seven TLDs were distributed throughout each right chest wall phantom to give adequate representation of measured radiation doses. Point doses from the CMS Xio Registered-Sign treatment planning system (TPS) were calculated for each relevant TLD positions and results correlated. There were no significant difference between measured absorbed dose by TLD and calculated doses by the TPS (p > 0.05 (1-tailed). Dose accuracy of up to 2.21% was found. The deviations from the calculated absorbed doses were overall larger (3.4%) when wedges and bolus were used. 3D radiotherapy TPS is a useful and accurate tool to assess the accuracy of surface dose. Our studies have shown that radiation treatment accuracy expressed as a comparison between calculated doses (by TPS) and measured doses (by TLD dosimetry) can be accurately predicted for tangential treatment of the chest wall after mastectomy.

Wong, Sharon [National University of Singapore, Yong Loo Lin School of Medicine (Singapore); Back, Michael [Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales (Australia); Tan, Poh Wee; Lee, Khai Mun; Baggarley, Shaun [National University, Cancer Institute, Department of Radiation Oncology, National University, Hospital, Tower Block (Singapore); Lu, Jaide Jay, E-mail: mdcljj@nus.edu.sg [National University of Singapore, Yong Loo Lin School of Medicine (Singapore); National University, Cancer Institute, Department of Radiation Oncology, National University, Hospital, Tower Block (Singapore)

2012-07-01

25

Intranasal delivery of antiepileptic medications for treatment of seizures.  

PubMed

Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are all deemed medical emergencies. Mortality and worse neurologic outcome are directly associated with the duration of seizure activity. A number of recent reviews have described consensus statements regarding the pharmacologic treatment protocols for seizures when patients are in pre-hospital, institutional, and home-bound settings. Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection. Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures in the pre-hospital setting, when actively seizing patients arrive in the emergency room, and at home where caregivers treat their dependents. This review summarizes factors to consider when choosing a benzodiazepine for intranasal administration, including formulation and device considerations, pharmacology and pharmacokinetic/pharmacodynamic profiles. A review of the most relevant clinical studies in epilepsy patients will provide context for the relative success of this technique with a number of benzodiazepines and relatively less sophisticated nasal preparations. Neuropeptides delivered intranasally, crossing the blood-brain barrier via the olfactory system, may increase the availability of medications for treatment of epilepsy. Consequently, there remains a significant unmet medical need to serve the pharamcotherapeutic requirements of epilepsy patients through commercial development and marketing of intranasal antiepileptic products. PMID:19332330

Wermeling, Daniel P

2009-04-01

26

Dosimetric Impact of Interplay Effect on RapidArc Lung Stereotactic Treatment Delivery  

SciTech Connect

Purpose: Volumetric modulated arc therapy (RapidArc; Varian Medical Systems, Palo Alto, CA) allows fast delivery of stereotactic radiotherapy for Stage I lung tumors. We investigated discrepancies between the calculated and delivered dose distributions, as well as the dosimetric impact of leaf interplay with breathing-induced tumor motion. Methods and Materials: In 20 consecutive patients with Stage I lung cancer who completed RapidArc delivery, 15 had tumor motion exceeding 5 mm on four-dimensional computed tomography scan. Static and dynamic measurements were performed with Gafchromic EBT film (International Specialty Products Inc., Wayne, NJ) in a Quasar motion phantom (Modus Medical Devices, London, Ontario, Canada). Static measurements were compared with calculated dose distributions, and dynamic measurements were compared with the convolution of static measurements with sinusoidal motion patterns. Besides clinical treatment plans, additional cases were optimized to create excessive multileaf collimator modulation and delivered on the phantom with peak-to-peak motions of up to 25 mm. {gamma} Analysis with a 3% dose difference and 2- or 1-mm distance to agreement was used to evaluate the accuracy of delivery and the dosimetric impact of the interplay effect. Results: In static mode film dosimetry of the two-arc delivery in the phantom showed that, on average, fewer than 3% of measurements had {gamma} greater than 1. Dynamic measurements of clinical plans showed a high degree of agreement with the convolutions: for double-arc plans, 99.5% met the {gamma} criterion. The degree of agreement was 98.5% for the plans with excessive multileaf collimator modulations and 25 mm of motion. Conclusions: Film dosimetry shows that RapidArc accurately delivers the calculated dose distribution and that interplay between leaves and tumor motion is not significant for single-fraction treatments when RapidArc is delivered with two different arcs.

Ong, Chin Loon, E-mail: c.ong@vumc.n [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Verbakel, Wilko F.A.R.; Cuijpers, Johan P.; Slotman, Ben J.; Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)

2011-01-01

27

Clinical Practice Guideline for Accurate Diagnosis and Effective Treatment of Gastrointestinal Stromal Tumor in Korea  

PubMed Central

Despite their rarity in incidence and prevalence, gastrointestinal stromal tumors (GISTs) have emerged as a distinct and noteworthy pathogenetic entity. The clinical management of GISTs has rapidly evolved due to the recent elucidation of their oncogenic signal transduction pathway and the introduction of molecular-targeted therapies. Successful management of GISTs requires a multidisciplinary approach firmly based on an accurate histopathologic diagnosis. In 2007, the Korean GIST study group published the first guideline for optimal diagnosis and treatment of GISTs in Korea. The second version of the guideline was published in 2010. Herein, we provide the results of relevant clinical studies for the purpose of further revision to the guideline. We expect this new guideline will enhance the accuracy of diagnosis, as performed by members of the Korean associate of physicians involved in GIST patient care, thus improving the efficacy of treatment.

Kang, Hye Jin; Kim, Kyoung-Mee; Sohn, Taesung; Choi, Dongil; Ryu, Min-Hee; Kim, Woo Ho; Yang, Han-Kwang

2012-01-01

28

Novel periodontal drug delivery system for treatment of periodontitis.  

PubMed

A conceptually novel periodontal drug delivery system (DDS) is described that is intended for treatment of microbial infections associated with periodontitis. The DDS is a composite wafer with surface layers possessing adhesive properties, while the bulk layer consists of antimicrobial agents, biodegradable polymers, and matrix polymers. The wafers contain poly(lactic-co-glycolic acid) as the main bioerodible component used in the bulk layer and ethyl cellulose applied as a matrix polymer enabling diffusion-controlled release. Starch and other polymers in combination with AgNO(3) serve as coatings adhesive to the teeth. In vitro experiments demonstrate that the wafers are capable of zero-order release of antimicrobial agents such as silver nitrate, benzylpenicillin, and tetracycline, for over 4 weeks. PMID:11295218

Bromberg, L E; Buxton, D K; Friden, P M

2001-04-28

29

The use of a realistic VMAT delivery emulator to optimize dynamic machine parameters for improved treatment efficiency  

NASA Astrophysics Data System (ADS)

The delivery of volumetric modulated arc therapy (VMAT) requires the simultaneous movement of the linear accelerator gantry, multi-leaf collimators and jaws while the dose rate is varied. In this study, a VMAT delivery emulator was developed to accurately predict the characteristics of a given treatment plan, incorporating realistic parameters for gantry inertia and the variation in leaf speed with respect to gravity. The emulator was used to assess the impact of dynamic machine parameters on the delivery efficiency, using a set of prostate and head and neck VMAT plans. Initially, assuming a VMAT system with fixed dose rate bins, the allowable leaf and jaw speeds were increased and a significant improvement in treatment time and average dose rate was observed. The software was then adapted to simulate a VMAT system with continuously varying dose rate, and the increase in delivery efficiency was quantified, along with the impact of an increased leaf and jaw speed. Finally, a set of optimal dynamic machine parameters was derived assuming an idealized scenario in which the treatment is delivered in a single arc at constant maximum gantry speed.

Boylan, C. J.; Rowbottom, C. G.; Mackay, R. I.

2011-07-01

30

Simulation of gentamicin delivery for the local treatment of osteomyelitis.  

PubMed

In order to understand the effect of antibiotics delivery to bone tissue, by biodegradable polymeric drug disc, for the treatment of osteomyelitis, a three-dimensional simulation model is developed. The simulation investigates the effect of pressure-induced convection on drug distribution, by taking into account the pressure gradient that exists between capillaries and interstitial space, and also as a result of the surgical opening. The clotting process at the surgical opening is incorporated into the simulation, and the effect of clotting duration is investigated. The clotting duration for the baseline simulation is 2 days and it is observed that increasing this duration depresses the mean drug concentration in the marrow and cortical bone. The effect of double burst release profile is also studied and it is observed that drug concentration drops too rapidly after the first burst to provide any therapeutic effect. However, it is shown that the drug concentration after the second burst stays above the minimum inhibitory concentration of the bacteria for a longer period of time, than would have been observed for a mono-burst release. Inserting non-biodegradable polymethylmethacrylate (PMMA) beads into bone seems to cause a higher average concentration of drug in the marrow. However, this could be brought about by the difference in the geometry between the disc and the bead, and the amount of drug packed in each bead. Further simulations on the management of dead space shows the ineffectiveness of having the void filled up with surgical gel as it becomes an additional barrier to drug delivery to the infected tissues. PMID:15981276

Lee, Chian Guan; Fu, Yin-Chih; Wang, Chi-Hwa

2005-09-01

31

Asthma control cost-utility randomized trial evaluation (ACCURATE): the goals of asthma treatment  

PubMed Central

Background Despite the availability of effective therapies, asthma remains a source of significant morbidity and use of health care resources. The central research question of the ACCURATE trial is whether maximal doses of (combination) therapy should be used for long periods in an attempt to achieve complete control of all features of asthma. An additional question is whether patients and society value the potential incremental benefit, if any, sufficiently to concur with such a treatment approach. We assessed patient preferences and cost-effectiveness of three treatment strategies aimed at achieving different levels of clinical control: 1. sufficiently controlled asthma 2. strictly controlled asthma 3. strictly controlled asthma based on exhaled nitric oxide as an additional disease marker Design 720 Patients with mild to moderate persistent asthma from general practices with a practice nurse, age 18-50 yr, daily treatment with inhaled corticosteroids (more then 3 months usage of inhaled corticosteroids in the previous year), will be identified via patient registries of general practices in the Leiden, Nijmegen, and Amsterdam areas in The Netherlands. The design is a 12-month cluster-randomised parallel trial with 40 general practices in each of the three arms. The patients will visit the general practice at baseline, 3, 6, 9, and 12 months. At each planned and unplanned visit to the general practice treatment will be adjusted with support of an internet-based asthma monitoring system supervised by a central coordinating specialist nurse. Patient preferences and utilities will be assessed by questionnaire and interview. Data on asthma control, treatment step, adherence to treatment, utilities and costs will be obtained every 3 months and at each unplanned visit. Differences in societal costs (medication, other (health) care and productivity) will be compared to differences in the number of limited activity days and in quality adjusted life years (Dutch EQ5D, SF6D, e-TTO, VAS). This is the first study to assess patient preferences and cost-effectiveness of asthma treatment strategies driven by different target levels of asthma control. Trial registration Netherlands Trial Register (NTR): NTR1756

2011-01-01

32

[Treatment of rheumatic diseases with intraarticular drug delivery systems].  

PubMed

Present work provides an overall study about the types and the medicinal treatment of the rheumatic diseases especially the intraarticular formulations. Due to the localized nature of the joint, intraarticular injections are very favourable drug delivery systems. It has a big advantage over the oral medication; the systemic side effects are kept away. The review shows two types of the rheumatic diseases on the example of the healthy joint: the joint damage (osteoarthritis) and the inflamed joint (rheumatoid arthritis). There are many active ingredients for the treatment of the rheumatic diseases but the number of the intraarticular products is limited. At present are only formulations with hyaluronic acid or glucocorticoid on the market. Several physiological and biopharmaceutical aspects must be considered for the design of intraarticular injections. During and after the production many quality requirements have to be complied. On the market the formulations in solution or in suspension are available, which provide a short-term effect. The aim of the developments is to achieve long-term effect based on nano- or microparticles. PMID:21800713

Szabó, Andrea; Zelkó, Romána; Antal, István

2011-01-01

33

A new transdermal delivery system for pilocarpine in glaucoma treatment.  

PubMed

We studied the intraocular pressure (IOP)-lowering effect and the side effects of a new transdermal delivery system (TDS) containing pilocarpine. After giving their written informed consent, patients were randomly assigned to receive a pilocarpine TDS or a placebo TDS. Two patches, each containing 30 mg of pilocarpine or placebo, were applied to the supraclavicular skin of 24 patients. The IOP was recorded before and at +12, 16, and 20 h after application. Plasma samples were analyzed for pilocarpine before treatment and 12 and 20 h later via high-performance liquid chromatography. The amount of drug remaining on the dermal patches was analyzed at 20 h. The mean IOP recorded before application was 22.7 +/- 5.8 mmHg. As compared with the placebo TDS, the pilocarpine TDS did not significantly reduce IOP at 12, 16, or 20 h after application (P = 0.42). The mean plasma concentrations were 2.9 ng/ml at 12 h and 1.3 ng/ml at 20 h. The verum TDS showed a residual mean drug concentration of 35.3 mg pilocarpine on the TDS. A substantial amount of pilocarpine was released from the TDS to the dermis, causing detectable plasma levels of pilocarpine at 12 and 20 h after administration. The pilocarpine TDS is a new nonocular pharmaceutical device that should avoid the side effects well known in glaucoma treatment when conventional eye drops are used. PMID:8911949

Dinslage, S; Diestelhorst, M; Hille, T; Otto, K

1996-09-01

34

An accurate calibration method of the multileaf collimator valid for conformal and intensity modulated radiation treatments  

NASA Astrophysics Data System (ADS)

Because for IMRT treatments the required accuracy on leaf positioning is high, conventional calibration methods may not be appropriate. The aim of this study was to develop the tools for an accurate MLC calibration valid for conventional and IMRT treatments and to investigate the stability of the MLC. A strip test consisting of nine adjacent segments 2 cm wide, separated by 1 mm and exposed on Kodak X-Omat V films at Dmax depth, was used for detecting leaf-positioning errors. Dose profiles along the leaf-axis were taken for each leaf-pair. We measured the dose variation on each abutment to quantify the relative positioning error (RPE) and the absolute position of the abutment to quantify the absolute positioning error (APE). The accuracy of determining the APE and RPE was 0.15 and 0.04 mm, respectively. Using the RPE and the APE the MLC calibration parameters were calculated in order to obtain a flat profile on the abutment at the correct position. A conventionally calibrated Elekta MLC was re-calibrated using the strip test. The stability of the MLC and leaf-positioning reproducibility was investigated exposing films with 25 adjacent segments 1 cm wide during three months and measuring the standard deviation of the RPE values. A maximum shift over the three months of 0.27 mm was observed and the standard deviation of the RPE values was 0.11 mm.

Sastre-Padro, Maria; van der Heide, Uulke A.; Welleweerd, Hans

2004-06-01

35

Reconstruction of applicator positions from multiple-view images for accurate superficial hyperthermia treatment planning.  

PubMed

In the current clinical practice, prior to superficial hyperthermia treatments (HT), temperature probes are placed in tissue to document a thermal dose. To investigate whether the painful procedure of catheter placement can be replaced by superficial HT planning, we study if the specific absorption rate (SAR) coverage is predictive for treatment outcome. An absolute requirement for such a study is the accurate reconstruction of the applicator setup. The purpose of this study was to investigate the feasibility of the applicator setup reconstruction from multiple-view images. The accuracy of the multiple-view reconstruction method has been assessed for two experimental setups using six lucite cone applicators (LCAs) representing the largest array applied at our clinic and also the most difficult scenario for the reconstruction. For the two experimental setups and 112 distances, the mean difference between photogrametry reconstructed and manually measured distances was 0.25 ± 0.79 mm (mean±1 standard deviation). By a parameter study of translation T (mm) and rotation R (°) of LCAs, we showed that these inaccuracies are clinically acceptable, i.e. they are either from ±1.02 mm error in translation or ±0.48° in rotation, or combinations expressed by 4.35R(2) + 0.97T(2) = 1. We anticipate that such small errors will not have a relevant influence on the SAR distribution in the treated region. The clinical applicability of the procedure is shown on a patient with a breast cancer recurrence treated with reirradiation plus superficial hyperthermia using the six-LCA array. The total reconstruction procedure of six LCAs from a set of ten photos currently takes around 1.5 h. We conclude that the reconstruction of superficial HT setup from multiple-view images is feasible and only minor errors are found that will have a negligible influence on treatment planning quality. PMID:22493169

Drizdal, T; Paulides, M M; Linthorst, M; van Rhoon, G C

2012-04-11

36

CPR methodology with new steady-state criterion and more accurate statistical treatment of channel bow  

SciTech Connect

An overview is given of existing CPR design criteria and the methods used in BWR reload analysis to evaluate the impact of channel bow on CPR margins. Potential weaknesses in today's methodologies are discussed. Westinghouse in collaboration with KKL and Axpo - operator and owner of the Leibstadt NPP - has developed an optimized CPR methodology based on a new criterion to protect against dryout during normal operation and with a more rigorous treatment of channel bow. The new steady-state criterion is expressed in terms of an upper limit of 0.01 for the dryout failure probability per year. This is considered a meaningful and appropriate criterion that can be directly related to the probabilistic criteria set-up for the analyses of Anticipated Operation Occurrences (AOOs) and accidents. In the Monte Carlo approach a statistical modeling of channel bow and an accurate evaluation of CPR response functions allow the associated CPR penalties to be included directly in the plant SLMCPR and OLMCPR in a best-estimate manner. In this way, the treatment of channel bow is equivalent to all other uncertainties affecting CPR. Emphasis is put on quantifying the statistical distribution of channel bow throughout the core using measurement data. The optimized CPR methodology has been implemented in the Westinghouse Monte Carlo code, McSLAP. The methodology improves the quality of dryout safety assessments by supplying more valuable information and better control of conservatisms in establishing operational limits for CPR. The methodology is demonstrated with application examples from the introduction at KKL. (authors)

Baumgartner, S. [Axpo AG, Parkstrasse 23, CH-5401 Baden (Switzerland); Bieli, R. [Kernkraftwerk Leibstadt AG, CH-5325 Leibstadt (Switzerland); Bergmann, U. C. [Westinghouse Electric Sweden AB, SE-721 63 Vaesteraas (Sweden)

2012-07-01

37

Development of a geometrically accurate imaging protocol at 3 Tesla MRI for stereotactic radiosurgery treatment planning  

NASA Astrophysics Data System (ADS)

The purpose of this study is to develop a geometrically accurate imaging protocol at 3 T magnetic resonance imaging (MRI) for stereotactic radiosurgery (SRS) treatment planning. In order to achieve this purpose, a methodology is developed to investigate the geometric accuracy and stability of 3 T MRI for SRS in phantom and patient evaluations. Forty patients were enrolled on a prospective clinical trial. After frame placement prior to SRS, each patient underwent 3 T MRI after 1.5 T MRI and CT. MR imaging protocols included a T1-weighted gradient echo sequence and a T2-weighted spin echo sequence. Phantom imaging was performed on 3 T prior to patient imaging using the same set-up and imaging protocols. Geometric accuracy in patients and phantoms yielded comparable results for external fiducial reference deviations and internal landmarks between 3 T and 1.5 T MRI (mean <=0.6 mm; standard deviation <=0.3 mm). Mean stereotactic reference deviations between phantoms and patients correlated well (T1: R = 0.79; T2: R = 0.84). Statistical process control analysis on phantom QA data demonstrated the stability of our SRS imaging protocols, where the geometric accuracy of the 3 T SRS imaging protocol is operating within the appropriate tolerance. Our data provide evidence supporting the spatial validity of 3 T MRI for targeting SRS under imaging conditions investigated. We have developed a systematic approach to achieve confidence on the geometric integrity of a given imaging system/technique for clinical integration in SRS application.

Zhang, B.; MacFadden, D.; Damyanovich, A. Z.; Rieker, M.; Stainsby, J.; Bernstein, M.; Jaffray, D. A.; Mikulis, D.; Ménard, C.

2010-11-01

38

A Monte Carlo tool for evaluating VMAT and DIMRT treatment deliveries including planar detectors.  

PubMed

The aim of this work is to describe and validate a new general research tool that performs Monte Carlo (MC) simulations for volumetric modulated arc therapy (VMAT) and dynamic intensity modulated radiation therapy (DIMRT), simultaneously tracking dose deposition in both the patient CT geometry and an arbitrary planar detector system. The tool is generalized to handle either entrance or exit detectors and provides the simulated dose for the individual control-points of the time-dependent VMAT and DIMRT deliveries. The MC simulation tool was developed with the EGSnrc radiation transport. For the individual control point simulation, we rotate the patient/phantom volume only (i.e. independent of the gantry and planar detector geometries) using the gantry angle in the treatment planning system (TPS) DICOM RP file such that each control point has its own unique phantom file. After MC simulation, we obtained the total dose to the phantom by summing dose contributions for all control points. Scored dose to the sensitive layer of the planar detector is available for each control point. To validate the tool, three clinical treatment plans were used including VMAT plans for a prostate case and a head-and-neck case, and a DIMRT plan for a head-and-neck case. An electronic portal imaging device operated in 'movie' mode was used with the VMAT plans delivered to cylindrical and anthropomorphic phantoms to validate the code using an exit detector. The DIMRT plan was delivered to a novel transmission detector, to validate the code using an entrance detector. The total MC 3D absolute doses in patient/phantom were compared with the TPS doses, while 2D MC doses were compared with planar detector doses for all individual control points, using the gamma evaluation test with 3%/3 mm criteria. The MC 3D absolute doses demonstrated excellent agreement with the TPS doses for all the tested plans, with about 95% of voxels having ? <1 for the plans. For planar dosimetry image comparisons, we defined an acceptable pass rate of >90% of percentage pixels with ? <1. We found that over 90% of control points in the plans passed this criterion. In general, our results indicate that the simulation tool is suitable for accurately calculating both patient/phantom doses and planar doses for VMAT dose delivery. The tool will be valuable to check performance and advance the development of in vivo planar detectors for use in measurement-based VMAT dose verification. In addition, the tool can be useful as an independent research tool for VMAT commissioning of the TPS and delivery system. PMID:23640066

Asuni, G; van Beek, T A; Venkataraman, S; Popescu, I A; McCurdy, B M C

2013-05-02

39

Large-scale extraction of accurate drug-disease treatment pairs from biomedical literature for drug repurposing  

PubMed Central

Background A large-scale, highly accurate, machine-understandable drug-disease treatment relationship knowledge base is important for computational approaches to drug repurposing. The large body of published biomedical research articles and clinical case reports available on MEDLINE is a rich source of FDA-approved drug-disease indication as well as drug-repurposing knowledge that is crucial for applying FDA-approved drugs for new diseases. However, much of this information is buried in free text and not captured in any existing databases. The goal of this study is to extract a large number of accurate drug-disease treatment pairs from published literature. Results In this study, we developed a simple but highly accurate pattern-learning approach to extract treatment-specific drug-disease pairs from 20 million biomedical abstracts available on MEDLINE. We extracted a total of 34,305 unique drug-disease treatment pairs, the majority of which are not included in existing structured databases. Our algorithm achieved a precision of 0.904 and a recall of 0.131 in extracting all pairs, and a precision of 0.904 and a recall of 0.842 in extracting frequent pairs. In addition, we have shown that the extracted pairs strongly correlate with both drug target genes and therapeutic classes, therefore may have high potential in drug discovery. Conclusions We demonstrated that our simple pattern-learning relationship extraction algorithm is able to accurately extract many drug-disease pairs from the free text of biomedical literature that are not captured in structured databases. The large-scale, accurate, machine-understandable drug-disease treatment knowledge base that is resultant of our study, in combination with pairs from structured databases, will have high potential in computational drug repurposing tasks.

2013-01-01

40

Designated case managers as facilitators of medical and psychosocial service delivery in addiction treatment programs  

Microsoft Academic Search

This study examines whether having designated case management staff facilitates delivery of comprehensive medical and psychosocial services in substance abuse treatment programs. A multilevel, prospective cohort study of 2829 clients admitted to selected substance abuse treatment programs was used to study clients from long-term residential, outpatient, and methadone treatment modalities. Program directors reported whether the program had staff designated as

Peter D. Friedmann; James C. Hendrickson; Dean R. Gerstein; Zhiwei Zhang

2004-01-01

41

Delivery.  

PubMed

Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry. PMID:23852646

Miller, Thomas A

2013-08-09

42

Direct gene delivery strategies for the treatment of rheumatoid arthritis.  

PubMed

Gene therapy offers a novel and innovative approach to the delivery of therapeutic proteins to the joints of patients with arthritis. Several viral vectors, including adenovirus, adeno-associated virus, retrovirus and herpes simplex virus, are capable of delivering exogenous cDNAs to the synovial lining, enabling effective levels of intra-articular transgene expression following direct injection to the joint. The expression of certain gene products has proven to be sufficient to inhibit the progression of disease in animals with experimental arthritis. Non-viral methods of gene transfer, however, are less satisfactory, and are limited by toxicity and transience of expression. Although the principle of direct gene delivery to the joint has been demonstrated, maintaining persistent intra-articular transgene expression remains a challenge. PMID:11182599

Ghivizzani, S C.; Oligino, T J.; Glorioso, J C.; Robbins, P D.; Evans, C H.

2001-03-01

43

Airways delivery of rifampicin microparticles for the treatment of tuberculosis  

Microsoft Academic Search

A Mycobacterium tuberculosis (H37Rv)-infected guinea pig model was used to screen for targeted delivery to the lungs by insufflation (with lactose excipient) or nebulization, of either rifampicin alone, rifampicin within poly(lactide-co-glycolide) microspheres (R-PLGA) or polymer microparticles alone (PLGA). Animals treated with single and double doses of R-PLGA microspheres exhibited significantly reduced numbers of viable bacteria, inflamma- tion and lung damage

Sandra Suarez; Patrick O'Hara; Masha Kazantseva; Christian E. Newcomer; Roy Hopfer; David N. McMurray; Anthony J. Hickey

2001-01-01

44

Direct gene delivery strategies for the treatment of rheumatoid arthritis  

Microsoft Academic Search

Gene therapy offers a novel and innovative approach to the delivery of therapeutic proteins to the joints of patients with arthritis. Several viral vectors, including adenovirus, adeno-associated virus, retrovirus and herpes simplex virus, are capable of delivering exogenous cDNAs to the synovial lining, enabling effective levels of intra-articular transgene expression following direct injection to the joint. The expression of certain

Steven C Ghivizzani; Thomas J Oligino; Joseph C Glorioso; Paul D Robbins; Christopher H Evans

2001-01-01

45

Skin laser treatments enhancing transdermal delivery of ALA.  

PubMed

Drug delivery across skin has been limited due to barrier properties of the skin, especially those of the stratum corneum (SC). Use of the laser radiation has been suggested for the controlled removal of the SC. The purpose of this study was to study in vitro the influence of infrared radiation from the erbium:yttrium-aluminum-garnet (Er:YAG) laser (??=?2940 ?nm), and visible from the 2nd harmonic of a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (??=?532? nm) on transdermal delivery of 5-aminolevulinic acid (ALA). Pinna skin of the inner side of rabbit ear was used for skin permeation. The light sources were an Er:YAG laser (Key III Plus KaVo) and a Q-switched Nd:YAG laser (Lotis TII SL-2132). Permeation study, morphological and structural skin examination by histology and differential scanning calorimetry (DSC) were carried out. Permeation profiles and histological observations obtained after irradiation with infrared and visible laser radiation differed due to different biophysical effects on irradiated skin. Wavelength of 2940 ?nm required lower energy contribution to produce the same level of permeation than visible radiation at 532 ?nm. Structural analysis by DSC shows a selective impact on the lipidic structure. Laser pretreatment enhanced the delivery of ALA trough the skin by SC ablation. PMID:20589948

Gómez, Clara; Costela, Ángel; García-Moreno, Inmaculada; Llanes, Felipe; Teijón, José M; Blanco, M Dolores

2010-06-29

46

Polymeric nanoparticles-based topical delivery systems for the treatment of dermatological diseases.  

PubMed

Human skin not only functions as a permeation barrier (mainly because of the stratum corneum layer) but also provides a unique delivery pathway for therapeutic and other active agents. These compounds penetrate via intercellular, intracellular, and transappendageal routes, resulting in topical delivery (into skin strata) and transdermal delivery (to subcutaneous tissues and into the systemic circulation). Passive and active permeation enhancement methods have been widely applied to increase the cutaneous penetration. The pathology, pathogenesis, and topical treatment approaches of dermatological diseases, such as psoriasis, contact dermatitis, and skin cancer, are then discussed. Recent literature has demonstrated that nanoparticles-based topical delivery systems can be successful in treating these skin conditions. The studies are reviewed starting with the nanoparticles based on natural polymers especially chitosan, followed by those made of synthetic, degradable (aliphatic polyesters), and nondegradable (polyacrylates) polymers; emphasis is given to nanospheres made of polymers derived from naturally occurring metabolites, the tyrosine-derived nanospheres (TyroSpheres™). In summary, the nanoparticles-based topical delivery systems combine the advantages of both the nanosized drug carriers and the topical approach, and are promising for the treatment of skin diseases. For the perspectives, the penetration of ultra-small nanoparticles (size smaller than 40 nm) into skin strata, the targeted delivery of the encapsulated drugs to hair follicle stem cells, and the combination of nanoparticles and microneedle array technologies for special applications such as vaccine delivery are discussed. PMID:23386536

Zhang, Zheng; Tsai, Pei-Chin; Ramezanli, Tannaz; Michniak-Kohn, Bozena B

2013-02-05

47

Aerosol delivery devices in the treatment of asthma.  

PubMed

Nebulizers convert solutions or suspensions into aerosols with a particle size that can be inhaled into the lower respiratory tract. There are pneumatic jet nebulizers, ultrasonic nebulizers, and mesh nebulizers. Newer nebulizer designs are breath-enhanced, breath-actuated, or have aerosol-storage bags to minimize aerosol loss during exhalation. Nebulizers can be used with helium-oxygen mixture and can be used for continuous aerosol delivery. Increased attention has recently been paid to issues related to the use of a facemask with a nebulizer. The pressurized metered-dose inhaler (pMDI) is a very commonly used device for aerosol delivery. There are press-and-breathe and breath-actuated pMDI designs. Issues related to pMDIs that have received increasing attention are the conversion to hydrofluoroalkane propellant and the use of dose counters. Many patients have poor pMDI technique. Valved holding chambers and spacers are used to improve pMDI technique and to decrease aerosol deposition in the upper airway. In recent years increasing attention has been paid to the issues of electrostatic charge and facemasks related to valved holding chambers. Many newer formulations for inhalation have been released in dry-powder inhalers, which are either unit-dose or multi-dose inhalers. Systematic reviews and meta-analyses have suggested that each of these aerosol delivery devices can work equally well in patients who can use them correctly. However, many patients use these devices incorrectly, so proper patient education in their use is critical. PMID:18501026

Hess, Dean R

2008-06-01

48

Advanced radiation treatment planning and delivery approaches for treatment of lung cancer.  

PubMed

Great technologic progress has been made in the last decade in the radiation treatment of lung cancer. In particular, the widespread use of 3D conformal therapy has the potential to escalate the dose to the tumor while sparing dose to normal tissue. Current technology, however, has yet to impact local control and survival. It could be hypothesized that this is due to geographic misses because of poor target definition, movement of the tumor due to respiration, and dose/ fractionation levels. Several emerging technologies that are described in this article have the potential to address these problems, with results expected in the near future. The technical delivery of radiation has not reached its limit. PMID:15005291

Martel, Mary K

2004-02-01

49

Convection-enhanced delivery of camptothecin-loaded polymer nanoparticles for treatment of intracranial tumors  

Microsoft Academic Search

Direct delivery of chemotherapy agents to the brain via degradable polymer delivery systems—such as Gliadel®—is a clinically\\u000a proven method for treatment of glioblastoma multiforme, but there are important limitations with the current technology—including\\u000a the requirement for surgery, profound local tissue toxicity, and limitations in diffusional penetration of agents—that limit\\u000a its application and effectiveness. Here, we demonstrate another technique for direct,

Andrew J. Sawyer; Jennifer K. Saucier-Sawyer; Carmen J. Booth; Jie Liu; Toral Patel; Joseph M. Piepmeier; W. Mark Saltzman

2011-01-01

50

Image-guided convection-enhanced delivery platform in the treatment of neurological diseases  

Microsoft Academic Search

Summary  Convection-enhanced delivery (CED) of substances within the human brain is becoming a more frequent experimental treatment\\u000a option in the management of brain tumors, and more recently in phase 1 trials for gene therapy in Parkinson’s disease (PD).\\u000a Benefits of this intracranial drug-transfer technology include a more efficient delivery of large volumes of therapeutic agent\\u000a to the target region when compared

Massimo S. Fiandaca; John R. Forsayeth; Peter J. Dickinson; Krystof S. Bankiewicz

2008-01-01

51

The Impact of Advanced Technologies on Treatment Deviations in Radiation Treatment Delivery  

SciTech Connect

Purpose: To assess the impact of new technologies on deviation rates in radiation therapy (RT). Methods and Materials: Treatment delivery deviations in RT were prospectively monitored during a time of technology upgrade. In January 2003, our department had three accelerators, none with 'modern' technologies (e.g., without multileaf collimators [MLC]). In 2003 to 2004, we upgraded to five new accelerators, four with MLC, and associated advanced capabilities. The deviation rates among patients treated on 'high-technology' versus 'low-technology' machines (defined as those with vs. without MLC) were compared over time using the two-tailed Fisher's exact test. Results: In 2003, there was no significant difference between the deviation rate in the 'high-technology' versus 'low-technology' groups (0.16% vs. 0.11%, p = 0.45). In 2005 to 2006, the deviation rate for the 'high-technology' groups was lower than the 'low-technology' (0.083% vs. 0.21%, p = 0.009). This difference was caused by a decline in deviations on the 'high-technology' machines over time (p = 0.053), as well as an unexpected trend toward an increase in deviations over time on the 'low-technology' machines (p = 0.15). Conclusions: Advances in RT delivery systems appear to reduce the rate of treatment deviations. Deviation rates on 'high-technology' machines with MLC decline over time, suggesting a learning curve after the introduction of new technologies. Associated with the adoption of 'high-technology' was an unexpected increase in the deviation rate with 'low-technology' approaches, which may reflect an over-reliance on tools inherent to 'high-technology' machines. With the introduction of new technologies, continued diligence is needed to ensure that staff remain proficient with 'low-technology' approaches.

Marks, Lawrence B. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)], E-mail: lawrence.marks@duke.edu; Light, Kim L.; Hubbs, Jessica L.; Georgas, Debra L.; Jones, Ellen L. [Department of Radiation Oncology, Duke University Medical Center, Durham, C (United States); Wright, Melanie C. [Department of Anesthesiology, Duke University Medical Center, Durham, NC (United States); Willett, Christopher G.; Yin Fangfang [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2007-12-01

52

Delays in treatment of pediatric appendicitis: a more accurate variable for measuring pediatric healthcare inequalities?  

PubMed

Racial and socioeconomic factors may cause barriers to healthcare access that result in delayed treatment. Because perforated appendicitis (PA) in children is thought to result from delays in treatment, it is often used as an index of barrier to access. Recent literature suggests that PA is not an inevitable consequence of delayed treatment, so it may not be the best marker for evaluating such barriers. Therefore we investigated whether racial and socioeconomic factors led directly to delays in treatment. We performed a retrospective study of 667 children undergoing appendectomy in a tertiary care center over 12.5 years. Univariate and multivariable regression analyses were used to determine if racial and socioeconomic variables were associated with increased risk of PA and increased risk of symptom duration greater than 48 hours. Hispanic children have higher rates of PA regardless of delays in treatment whereas Black children had higher PA rates likely due to delays in treatment. These differences were not from socioeconomic factors in our cohort. PA, a heterogeneous disease whose course is determined by multiple factors, is not a good metric for evaluation healthcare disparities in the pediatric population. Delays in treatment may be a more appropriate measure of healthcare inequalities in children. PMID:24069980

Ladd, Mitchell R; Pajewski, Nicholas M; Becher, Robert D; Swanson, John M; Gallaher, Jared R; Pranikoff, Thomas; Neff, Lucas P

2013-09-01

53

Maimonides: an early but accurate view on the treatment of haemorrhoids  

PubMed Central

Moses Maimonides was not only one of the most influential religious figures of the middle ages, but also a pioneer in a wide variety of medical practices. A brief history of his life, and what is known about his medical education, is given here. His paper on haemorrhoids is summarised, as well as a review of the current understanding of the pathogenesis, prevention and treatment of this common condition. The comparison of Maimonides' writings to modern understanding of not only the prevention and treatment of haemorrhoids, but also his approach to the patient as a whole in terms of pre? and postoperative care, demonstrate how ahead of his time this great philosopher was.

Magrill, Dan; Sekaran, Prabhu

2007-01-01

54

Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy  

SciTech Connect

Purpose: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. Methods: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. Results: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 {+-} 35 patients. Conclusions: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use factor of beam delivery parameters varies by disease site. Further improvements in efficiency may be realized in the equipment- and patient-related processes of treatment.

Suzuki, Kazumichi; Gillin, Michael T.; Sahoo, Narayan; Zhu, X. Ronald; Lee, Andrew K.; Lippy, Denise [Departments of Radiation Physics and Radiation Oncology, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); The Proton Therapy Center Houston, Ltd., L.L.P., 1840 Old Spanish Trail, Houston, Texas 77054 (United States)

2011-07-15

55

Anorexia nervosa and bulimia in dancers. Accurate diagnosis and treatment planning.  

PubMed

Ballet dancers have an increased risk of developing anorexia nervosa, perhaps because of their preoccupation with appearance and body shape related to their career. The author lists the early warning signs of anorexia nervosa and bulimia in dancers. Techniques are described to assist the practitioner in differentiating the normal dieting dancer from the anorectic dancer. The author emphasizes strategic treatment planning with anorectic dancers who initially deny the severity of their illness. PMID:6580964

Maloney, M J

1983-11-01

56

Transdermal delivery of sumatriptan for the treatment of acute migraine  

Microsoft Academic Search

Summary  Migraine is a common, multisymptom disorder that can severely impact the daily activities of migraineurs. Triptans (primarily\\u000a sumatriptan) are the most commonly prescribed treatment for migraine and are considered a relatively safe and effective initial\\u000a therapy. Unfortunately, current sumatriptan formulations (i.e., oral, nasal, subcutaneous) may be associated with limitations\\u000a that can result in patients’ delaying or avoiding treatment. For oral

Mark W. Pierce

2010-01-01

57

Pancreatic Cancer: Pathobiology, Treatment Options, and Drug Delivery  

Microsoft Academic Search

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. The high mortality rate is partly due to\\u000a lack of effective treatments. This review summarizes the pathobiology and current treatment options for pancreatic cancer.\\u000a Moreover, the review discusses the opportunities of developing novel therapies for pancreatic cancer provided by the progress\\u000a in understanding the genetic mutations, tumor

Jing Li; M. Guillaume Wientjes; Jessie L.-S. Au

2010-01-01

58

[Antenatal corticosteroids in respiratory distress syndrome prevention: efficacy in relation to treatment--delivery interval].  

PubMed

Antenatal corticosteroids given to women, who are 24 to 34 weeks pregnant and may deliver within the next 24 hours to 7 days, are associated with significant reduction in rates of respiratory distress syndrome, intraventricular hemorrhage and mortality of pre-term babies. The aim of this study is assessment of antenatal corticosteroid effectiveness in reduction of RDS incidence in optimal delivery-treatment interval, in comparison to babies delivered before and after the optimal treatment interval has elapsed. This investigation included 80 pre-term babies between 26 and 34 gestational weeks whose mothers received corticosteroids before delivery. Control group consisted of 92 children of the same gestational age, whose mothers did not received corticosteroids antenatally. Babies of diabetic mothers, babies with IUGR and babies with congenital abnormalities were excluded. RDS was significantly less frequent in babies antenatally treated by corticosteroids (x2 31,473 p < 0.0001 coefficient contingency 0.366) then in babies whose mothers did not received corticosteroids before delivery. The majority of babies, 54.67% (p < 0.01) were born in optimal interval, 24 hours to 7 days from the beginning of the treatment, 32.0% (24/75) children were born within 24 hours and 13.3% (10/75) were born more then 7 days after the start of treatment. Comparing the incidence of RDS between groups of children born in optimal treatment-delivery interval (1 -7 days) and in the group of children born within 24 hours or after 7 days from the beginning of the treatment, no significant difference was found. The effect was clinically comparable, which suggests the possibility of reduction treatment-delivery interval in acute clinical conditions. PMID:20088174

Helji?, Suada; Maksi?, Hajrija; Misanovi?, Verica; Dizdarevi?, Jadranka

2009-01-01

59

Transdermal delivery of treatment for Alzheimer's disease: development, clinical performance and future prospects.  

PubMed

There is increasing interest in the potential of transdermal drug delivery systems for the treatment of neurological disorders, especially in the elderly. In this population, the higher incidence of chronic diseases, such as diabetes mellitus, cardiovascular disease, neurological disease and chronic pain, has dramatically increased the need for long-term medications. Additionally, elderly patients often have a combination of several chronic diseases, meaning drug delivery, drug-drug interactions, absorption/blood concentrations, toxicity and compliance are of concern for patients as well as for their caregivers and physicians. Recent efforts have focused on developing pharmaceutical preparations that overcome these issues. For example, rate-controlled drug delivery systems have been under active development. Transdermal drug delivery systems have been developed to deliver phenserine, rivastigmine, nicotine and estradiol for the management of cognitive and behavioural dysfunctions in patients with Alzheimer's disease because this form of administration has several advantages, including maintenance of sustained therapeutic plasma concentrations of drugs, easy application and reduced systemic adverse effects. Thus, transdermal drug delivery for elderly patients offers promise as the ideal therapeutic approach to treating Alzheimer's disease.This article reviews the technical principles underlying the development of transdermal drug delivery systems, focusing on cholinesterase inhibitors, and the prospects for future development. The clinical performance of transdermal patches, again with emphasis on cholinesterase inhibitors, is also reviewed. PMID:18729547

Chan, Agnes L F; Chien, Yie W; Jin Lin, Shun

2008-01-01

60

An Efficient and Accurate Formalism for the Treatment of Large Amplitude Intramolecular Motion  

PubMed Central

We propose a general approach to describe large amplitude motions (LAM) with multiple degrees of freedom (DOF) in molecules or reaction intermediates, which is useful for the computation of thermochemical or kinetic data. The kinetic part of the LAM Lagrangian is derived using a Z-matrix internal coordinate representation within a new numerical procedure. This derivation is exact for a classical system, and the uncertainties on the prediction of observable quantities largely arise from uncertainties on the LAM potential energy surface (PES) itself. In order to rigorously account for these uncertainties, we present an approach based on Bayesian theory to infer a parametrized physical model of the PES using ab initio calculations. This framework allows for quantification of uncertainties associated with a PES model as well as the forward propagation of these uncertainties to the quantity of interest. A selection and generalization of some treatments accounting for the coupling of the LAM with other internal or external DOF are also presented. Finally, we discuss and validate the approach with two applications: the calculation of the partition function of 1,3-butadiene and the calculation of the high-pressure reaction rate of the CH3 + H ? CH4 recombination.

2012-01-01

61

Risk, Need, and Responsivity: Unrealized Potential for the International Delivery of Substance Abuse Treatment in Prison  

Microsoft Academic Search

Drawing from a strong Canadian and U.S. base of literature and an emergent base of scholarship from the United Kingdom, this article examines the delivery of substance abuse treatment in prisons and the determinants of prisoner access to and use of services. To date, multidisciplinary research provides evidence of supply-side programs driven by organizational factors that affect access and use;

Jennifer M. Jolley; John J. Kerbs

2010-01-01

62

Radio-Frequency Energy Delivery to the Anal Canal for the Treatment of Fecal Incontinence  

Microsoft Academic Search

PURPOSE: In this prospective study we investigated the feasibility, safety, and efficacy of radio-frequency energy delivery deep to the mucosa of the anal canal for the treatment of fecal incontinence. METHODS: We studied ten patients with fecal incontinence of varying causes. All patients underwent anoscopy, anorectal manometry, endorectal ultrasound, and pudendal nerve terminal motor latency testing at baseline and six

Takeshi Takahashi; Sandra Garcia-Osogobio; MiguelAngel Valdovinos; Wilbert Mass; Ramiro Jimenez; LuisAlfonso Jauregui; Juan Bobadilla; Carlos Belmonte; Peter S. Edelstein; David S. Utley

2002-01-01

63

Treatment Strategies for Self-Injurious Behavior in a Large Service-Delivery Network.  

ERIC Educational Resources Information Center

|The scope of psychoactive drug use within a statewide (Texas) institutional service delivery network was examined, with a focus on its role in the treatment of self-injurious behavior and other aberrant behaviors in the retarded. Insufficient use of behavioral technology and overuse of physical and chemical restraints were indicated. (Author/DB)|

Altmeyer, Bernd K.; And Others

1987-01-01

64

A system for percutaneous delivery of treatment with a fluoroscopically-guided robot  

Microsoft Academic Search

This manuscript discusses a prototype image-guided robotic system that is currently under development at The Johns Hopkins University. This system is intended to allow percutaneous delivery of surgical devices as well as therapeutic agents to soft tissue and bone lesions. The proposed system has many potential applications including the treatment of liver cancer, which is an attractive application of the

S. Schreiner; James H. Anderson; Russell H. Taylor; Janez Funda; Andrew Bzostek; Aaron C. Barnes

1997-01-01

65

QA Issues for Computer-Controlled Treatment Delivery: This Isn't Your Old R/V System Any More !  

PubMed Central

State of the art radiotherapy treatment delivery has changed dramatically over the last decade, moving from manual individual field setup and treatment to automated computer-controlled delivery of complex treatments including intensity modulated radiation therapy (IMRT) and other similarly complex delivery strategies. However, the quality assurance (QA) methods typically used to make sure treatment is performed precisely and correctly have not evolved in a similarly dramatic way. This paper reviews the old manual treatment process and use of record and verify systems, and describes differences with modern computer-controlled treatment delivery (CCTD). The process and technology used for CCTD are analyzed in terms of potential (and actual) problems as well as relevant published guidance on QA. The potential for improved QA for computer-controlled delivery is discussed.

Fraass, Benedick A.

2009-01-01

66

Intranasal delivery of antiepileptic medications for treatment of seizures  

Microsoft Academic Search

Summary  Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are all deemed medical emergencies. Mortality\\u000a and worse neurologic outcome are directly associated with the duration of seizure activity. A number of recent reviews have\\u000a described consensus statements regarding the pharmacologic treatment protocols for seizures when patients are in pre-hospital,\\u000a institutional, and home-bound settings. Benzodiazepines, such as lorazepam, diazepam, midazolam,

Daniel P. Wermeling

2009-01-01

67

A Novel Transdermal Plasmid-Dimethylsulfoxide Delivery Technique for Treatment of Psoriasis  

Microsoft Academic Search

Background: Psoriasis is a chronic and relapsing inflammatory skin disease associated with various immunologic abnormalities. Repeated subcutaneous injection of interleukin-4 (IL-4) has been established as an effective treatment to counteract psoriasis. Objective: We investigated whether gene therapy using IL-4 expression plasmid (pIL-4) via transdermal delivery was an alternative treatment for psoriasis. In our experiment, dimethylsulfoxide (DMSO) was used as a

Yan Zhang; Jiong Li; Chang-Yong Liu; Xi-Kun Zhou; Ji Qiu; Yin-Bing Zhang; Nong-Yu Huang; You Li; Xiang-Jun Chen; Xiao-Lei Li; Yong-Sheng Wang; Han-Suo Yang; Xian-Cheng Chen; Bing Kan; Yong-Qiu Mao; Hong-Xin Deng; Li Yang; Yan-Jun Wen; Xia Zhao; Yu-Quan Wei

2010-01-01

68

Social workers and delivery of evidence-based psychosocial treatments for substance use disorders.  

PubMed

Social workers encounter individuals with substance use disorders (SUDs) in a variety of settings. With changes in health care policy and a movement toward integration of health and behavioral health services, social workers will play an increased role vis-á-vis SUD. As direct service providers, administrators, care managers, and policy makers, they will select, deliver, or advocate for delivery of evidence-based SUD treatment practices. This article provides an overview of effective psychosocial SUD treatment approaches. In addition to describing the treatments, the article discusses empirical support, populations for whom the treatments are known to be efficacious, and implementation issues. PMID:23731420

Wells, Elizabeth A; Kristman-Valente, Allison N; Peavy, K Michelle; Jackson, T Ron

2013-01-01

69

Improved delivery of magnetic nanoparticles with chemotherapy cancer treatment  

NASA Astrophysics Data System (ADS)

Most nanoparticle-based cancer therapeutic strategies seek to develop an effective individual cancer cell or metastatic tumor treatment. Critical to the success of these therapies is to direct as much of the agent as possible to the targeted tissue while avoiding unacceptable normal tissue complications. In this light, three different cisplatinum/magnetic nanoparticle (mNP) administration regimens were investigated. The most important finding suggests that clinically relevant doses of cisplatinum result in a significant increase in the tumor uptake of systemically delivered mNP. This enhancement of mNP tumor uptake creates the potential for an even greater therapeutic ratio through the addition of mNP based, intracellular hyperthermia.

Petryk, Alicia A.; Giustini, Andrew J.; Gottesman, Rachel E.; Hoopes, P. Jack

2013-02-01

70

Local drug delivery for treatment of coronary and peripheral artery disease.  

PubMed

Local drug delivery (LDD), the direct application of a therapeutic agent to a focal location, has been used in cardiovascular interventions to prophylactically reduce neointimal hyperplasia and relieve clot burden. LDD allows targeted use of drugs whose toxicities inhibit their systemic use while stent delivery allows for consistent and prolonged delivery. Stents eluting limus family drugs or paclitaxel inhibit vascular smooth muscle cell hyperplasia and migration and clinical use of such stents have reduced restenosis rates after percutaneous coronary procedures. However, associated with the increased efficacy is an increased rate of late stent thrombosis associated with death and myocardial infarction. Recent innovations, including bioabsorbable polymers and completely bioabsorbable stents may expand the use of drug-eluting stents. In this review, we discuss the development, the clinical use, and the effects of LDD from balloon and stent-based platforms in the treatment of restenosis and thrombus. PMID:20553281

Gertz, Zachary M; Wilensky, Robert L

2010-06-11

71

Office laser delivery systems for the treatment of hypertrophic turbinates  

NASA Astrophysics Data System (ADS)

We present two different methods to treat hypertrophic turbinates in an office environment: (a) with the aid of 1 mm thin hollow waveguides transmitting a CO2 laser beam to produce char-free ablation of turbinate mucosa, and (b) with the aid of a 800 micron thin optical fiber transmitting low power Nd:YAG laser radiation to interstitially coagulate and shrink submucosal tissue. Char-free ablation of mucusal tissue: An office CO2 laser regularly used for LAUP in the treatment of snoring problems is operated in the Superpulse mode (peak power 350 W) at 8 W average power. The optical beam is coupled to angled and straight hollow waveguides. Ablation of inferior turbinates is performed within a few minutes under topical or local anesthesia. No post operative packing is required and the patient can return to normal activities. Healing is fast due to the highly controlled superficial thermal damage. Interstitial coagulation of inferior turbinates: Submucosal coagulation of tissue is attained with a flat 800 (mu) fiber longitudinally pushed and pulled while operating an Nd:YAG laser at 8 W power level. A 4 - 6 mm thin coagulated and shrunken volume of cylindrical shape is being produced with no damage to bones or mucosa. The procedure is fast and performed under local anesthesia. An analysis of both surgical techniques and clinical results with over 100 patients will be presented.

Krespi, Y. P.; Slatkine, Michael

1995-05-01

72

Intranasal clobazam delivery in the treatment of status epilepticus.  

PubMed

The aim of the present investigation was to prepare and characterize clobazam mucoadhesive microemulsion (CZMME) to assess brain drug uptake and protection against pentylenetetrazole (PTZ)-induced convulsions in mice. Clobazam microemulsion (CZME) and CZMME were prepared by titration method and characterized. Brain uptake and pharmacokinetic parameters were calculated from drug concentration in mice brain versus time plots following intranasal administration of radiolabeled CZME and CZMME, intravenous and intranasal administration of radiolabeled clobazam solution. Gamma scintigraphy imaging of rabbit brain following intranasal administration was performed. Formulations were investigated for the onset of seizures in PTZ-challenged mice. Brain targeting efficiency and direct nose-to-brain transport percentage for mucoadhesive microemulsion suggested an improved brain uptake following intranasal administration. The findings were supported by gamma scintigraphy images. Delay in onset of PTZ-induced seizures with CZMME compared with positive control and placebo-treated groups confirmed the improved brain uptake. However, extensive animal studies followed by clinical trials are necessary to develop a product suitable for emergencies of acute seizures in status epilepticus and patients suffering from drug tolerance and hepatic impairment on long-term use in treatment of epilepsy, schizophrenia, and anxiety. PMID:20799366

Florence, Kiruba; Manisha, Lalan; Kumar, Babbar Anil; Ankur, Kaul; Kumar, Mishra Anil; Ambikanandan, Misra

2010-08-26

73

Energy modulated electron therapy: Design, implementation, and evaluation of a novel method of treatment planning and delivery  

NASA Astrophysics Data System (ADS)

Energy modulated electron therapy (EMET) is a promising treatment modality that has the fundamental capabilities to enhance the treatment planning and delivery of superficially located targets. Although it offers advantages over x-ray intensity modulated radiation therapy (IMRT), EMET has not been widely implemented to the same level of accuracy, automation, and clinical routine as its x-ray counterpart. This lack of implementation is attributed to the absence of a remotely automated beam shaping system as well as the deficiency in dosimetric accuracy of clinical electron pencil beam algorithms in the presence of beam modifiers and tissue heterogeneities. In this study, we present a novel technique for treatment planning and delivery of EMET. The delivery is achieved using a prototype of an automated "few leaf electron collimator" (FLEC). It consists of four copper leaves driven by stepper motors which are synchronized with the x-ray jaws in order to form a series of collimated rectangular openings or "fieldlets". Based on Monte Carlo studies, the FLEC has been designed to serve as an accessory tool to the current accelerator equipment. The FLEC was constructed and its operation was fully automated and integrated with the accelerator through an in-house assembled control unit. The control unit is a portable computer system accompanied with customized software that delivers EMET plans after acquiring them from the optimization station. EMET plans are produced based on dose volume constraints that employ Monte Carlo pre-generated and patient-specific kernels which are utilized by an in-house developed optimization algorithm. The structure of the optimization software is demonstrated. Using Monte Carlo techniques to calculate dose allows for accurate modeling of the collimation system as well as the patient heterogeneous geometry and take into account their impact on optimization. The Monte Carlo calculations were validated by comparing them against output measurements with an ionization chamber. Comparisons with measurements using nearly energy-independent radiochromic films were performed to confirm the Monte Carlo calculation accuracy for 1-D and 2-D dose distributions. We investigated the clinical significance of EMET on cancer sites that are inherently difficult to plan with IMRT. Several parameters were used to analyze treatment plans where they show that EMET provides significant overall improvements over IMRT.

Al-Yahya, Khalid

74

The case for intraocular delivery of PPAR agonists in the treatment of diabetic retinopathy  

PubMed Central

Background Systemic therapeutics targeting the peroxisome proliferator-activated receptors have been found to be beneficial in the treatment of diabetic retinopathy. In this paper, we provide a rationale for the use of these therapeutics as intraocular agents. In addition, we introduce the peroxisome proliferator-activated receptors and describe their functions in response to the drugs. Discussion Based on the evidence of large-scale clinical studies investigating the systemic administration of fenofibrate, this ligand for peroxisome proliferator-activated receptor-? is potentially a good candidate for intraocular delivery. Here, we describe the mechanisms by which it might be acting to improve diabetic retinopathy, its relative safety and we speculate on how it could be developed for intraocular delivery. Summary In this paper, we provide a rationale for the further investigation of peroxisome proliferator-activated receptor-? agonists as intraocular agents for the treatment of diabetic retinopathy.

2012-01-01

75

Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors  

Microsoft Academic Search

The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin\\u000a in combination with radiotherapy for treatment of the F98 rat glioma. Tumor cells were implanted stereotactically into the\\u000a brains of syngeneic Fischer rats, and 13 or 17 d. later carboplatin (20 ?g\\/10 ?l) was administered by either CED over 30 min\\u000a or by Alzet

Weilian Yang; Tianyao Huo; Rolf F. Barth; Nilendu Gupta; Michael Weldon; John C. Grecula; Brian D. Ross; Benjamin A. Hoff; Ting-Chao Chou; Julia Rousseau; Hélène Elleaume

2011-01-01

76

Novel superparamagnetic core-shell nanoparticles for magnetic targeted drug delivery and hyperthermia treatment  

Microsoft Academic Search

The last few decades have witnessed a tremendous increase in the interest to use ferrofluids and ferrofluid-drug conjugates in magnetically guided drug delivery in loco regional treatment of cancer\\/tumor. In this paper, experiments on iron oxide (maghemite, ?-Fe2O3)-gold superparamagnetic core-shell nanoparticles conjugated to human serum albumin-drug complex are presented. Coating these nanoparticles with gold varies the shell thickness resulting in

P. Gangopadhyay; T. Verbiest; S. Gallet; E. Franz; A. Persoons

2005-01-01

77

Investigating end-to-end accuracy of image guided radiation treatment delivery using a micro-irradiator  

NASA Astrophysics Data System (ADS)

There is significant interest in delivering precisely targeted small-volume radiation treatments, in the pre-clinical setting, to study dose–volume relationships with tumour control and normal tissue damage. For these studies it is vital that image guidance systems and target positioning are accurately aligned (IGRT), in order to deliver dose precisely and accurately according to the treatment plan. In this work we investigate the IGRT targeting accuracy of the X-RAD 225 Cx system from Precision X-Ray using high-resolution 3D dosimetry techniques. Small cylindrical PRESAGE® dosimeters were used with optical-CT readout (DMOS) to verify the accuracy of 2.5, 1.0, and 5.0 mm X-RAD cone attachments. The dosimeters were equipped with four target points, visible on both CBCT and optical-CT, at which a 7-field coplanar treatment plan was delivered with the respective cone. Targeting accuracy (distance to agreement between the target point and delivery isocenter) and cone alignment (isocenter precision under gantry rotation) were measured using the optical-CT images. Optical-CT readout of the first 2.5 mm cone dosimeter revealed a significant targeting error of 2.1 ± 0.6 mm and a cone misalignment of 1.3 ± 0.1 mm. After the IGRT hardware and software had been recalibrated, these errors were reduced to 0.5 ± 0.1 and 0.18 ± 0.04 mm respectively, within the manufacturer specified 0.5 mm. Results from the 1.0 mm cone were 0.5 ± 0.3 mm targeting accuracy and 0.4 ± 0.1 mm cone misalignment, within the 0.5 mm specification. The results from the 5.0 mm cone were 1.0 ± 0.2 mm targeting accuracy and 0.18 ± 0.06 mm cone misalignment, outside of accuracy specifications. Quality assurance of small field IGRT targeting and delivery accuracy is a challenging task. The use of a 3D dosimetry technique, where targets are visible on both CBCT and optical-CT, enabled identification and quantification of a targeting error in 3D. After correction, the targeting accuracy of the irradiator was verified to be within 0.5 mm (or 1.0 mm for the 5.0 mm cone) and the cone alignment was verified to be within 0.2 mm (or 0.4 mm for the 1.0 mm cone). The PRESAGE®/DMOS system proved valuable for end-to-end verification of small field IGRT capabilities.

Rankine, L. J.; Newton, J.; Bache, S. T.; Das, S. K.; Adamovics, J.; Kirsch, D. G.; Oldham, M.

2013-11-01

78

Investigating end-to-end accuracy of image guided radiation treatment delivery using a micro-irradiator.  

PubMed

There is significant interest in delivering precisely targeted small-volume radiation treatments, in the pre-clinical setting, to study dose-volume relationships with tumour control and normal tissue damage. For these studies it is vital that image guidance systems and target positioning are accurately aligned (IGRT), in order to deliver dose precisely and accurately according to the treatment plan. In this work we investigate the IGRT targeting accuracy of the X-RAD 225 Cx system from Precision X-Ray using high-resolution 3D dosimetry techniques. Small cylindrical PRESAGE® dosimeters were used with optical-CT readout (DMOS) to verify the accuracy of 2.5, 1.0, and 5.0 mm X-RAD cone attachments. The dosimeters were equipped with four target points, visible on both CBCT and optical-CT, at which a 7-field coplanar treatment plan was delivered with the respective cone. Targeting accuracy (distance to agreement between the target point and delivery isocenter) and cone alignment (isocenter precision under gantry rotation) were measured using the optical-CT images. Optical-CT readout of the first 2.5 mm cone dosimeter revealed a significant targeting error of 2.1 ± 0.6 mm and a cone misalignment of 1.3 ± 0.1 mm. After the IGRT hardware and software had been recalibrated, these errors were reduced to 0.5 ± 0.1 and 0.18 ± 0.04 mm respectively, within the manufacturer specified 0.5 mm. Results from the 1.0 mm cone were 0.5 ± 0.3 mm targeting accuracy and 0.4 ± 0.1 mm cone misalignment, within the 0.5 mm specification. The results from the 5.0 mm cone were 1.0 ± 0.2 mm targeting accuracy and 0.18 ± 0.06 mm cone misalignment, outside of accuracy specifications. Quality assurance of small field IGRT targeting and delivery accuracy is a challenging task. The use of a 3D dosimetry technique, where targets are visible on both CBCT and optical-CT, enabled identification and quantification of a targeting error in 3D. After correction, the targeting accuracy of the irradiator was verified to be within 0.5 mm (or 1.0 mm for the 5.0 mm cone) and the cone alignment was verified to be within 0.2 mm (or 0.4 mm for the 1.0 mm cone). The PRESAGE®/DMOS system proved valuable for end-to-end verification of small field IGRT capabilities. PMID:24140983

Rankine, L J; Newton, J; Bache, S T; Das, S K; Adamovics, J; Kirsch, D G; Oldham, M

2013-10-18

79

Feasibility of automating insulin delivery for the treatment of type 1 diabetes.  

PubMed

An automated closed-loop insulin delivery system based on subcutaneous glucose sensing and subcutaneous insulin delivery was evaluated in 10 subjects with type 1 diabetes (2 men, 8 women, mean [+/-SD] age 43.4 +/- 11.4 years, duration of diabetes 18.2 +/- 13.5 years). Closed-loop control was assessed over approximately 30 h and compared with open-loop control assessed over 3 days. Closed-loop insulin delivery was calculated using a model of the beta-cell's multiphasic insulin response to glucose. Plasma glucose was 160 +/- 66 mg/dl at the start of closed loop and was thereafter reduced to 71 +/- 19 by 1:00 p.m. (preprandial lunch). Fasting glucose the subsequent morning on closed loop was not different from target (124 +/- 25 vs. 120 mg/dl, respectively; P > 0.05). Mean glucose levels were not different between the open and closed loop (133 +/- 63 vs. 133 +/- 52 mg/dl, respectively; P > 0.65). However, glucose was within the range 70-180 mg/dl 75% of the time under closed loop versus 63% for open loop. Incidence of biochemical hypoglycemia (blood glucose <60 mg/dl) was similar under the two treatments. There were no episodes of severe hypoglycemia. The data provide proof of concept that glycemic control can be achieved by a completely automated external closed-loop insulin delivery system. PMID:17130478

Steil, Garry M; Rebrin, Kerstin; Darwin, Christine; Hariri, Farzam; Saad, Mohammed F

2006-12-01

80

Postoperative Irradiation of Gynecologic Malignancies: Improving Treatment Delivery Using Aperture-Based Intensity-Modulated Radiotherapy  

SciTech Connect

Purpose: To evaluate dosimetric and treatment delivery advantages of aperture-based intensity-modulated radiotherapy (AB-IMRT) for the treatment of patients receiving whole pelvic radiotherapy for gynecologic malignancies. Methods and Materials: Nineteen patients undergoing pelvic radiotherapy after resection of endometrial cancers were selected. A 45-Gy dose was prescribed to the target volume delineated on a planning CT scan. An in-house inverse planning system, Ballista, was used to develop a treatment plan using aperture-based multileaf collimator segments. This approach was compared with conventional four-field, enlarged four-field, and static beamlet-based IMRT (BB-IMRT) techniques in terms of target coverage, dose-volume histogram statistics for surrounding normal tissues, and numbers of segments and monitor units (MU). Results: Three quarters (76.4%) of the planning target volume received the prescription dose with conventional four-field plans. With adequate target coverage, the Ballista plans significantly reduced the volume of bowel and bladder irradiated at the prescribed dose (p < 0.001), whereas the two approaches provided equivalent results for the rectum (p 0.5). On the other hand, AB-IMRT and BB-IMRT plans showed only small differences in dose-volume histogram statistics of unknown clinical impact, whereas Ballista plan delivery required on average 73% and 59% fewer segments and MU, respectively. Conclusion: With respect to conventional techniques, AB-IMRT for the treatment of gynecologic malignancies provides dosimetric advantages similar to those with BB-IMRT but with clear treatment delivery improvements.

Nadeau, Sylvain [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada) and Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada)]. E-mail: sylvainn@rrsb.nb.ca; Bouchard, Myriam [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Germain, Isabelle [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Raymond, Paul-Emile [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Beaulieu, Frederic [Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Beaulieu, Luc [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada); Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada); Roy, Rene [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada); Gingras, Luc [Departement de physique, de genie physique et d'optique, Universite Laval, Quebec, QC (Canada); Departement de radio-oncologie et Centre de recherche de l'Hotel-Dieu de Quebec, Centre Hospitalier Universitaire de Quebec, Hotel-Dieu de Quebec, Quebec, QC (Canada)

2007-06-01

81

Comparative analysis of the methods of drug and protein delivery for the treatment of cancer, genetic diseases and diagnostics.  

PubMed

The methods of protein and drug delivery for the treatment of cancer, genetic diseases and diagnostics were summarized. The potential of protein transduction is discussed and the recent developments in the field are reviewed. An overview is provided of the non-viral delivery methods such as liposomes, polymer-based delivery, cell-penetrating peptides, bacterial secretion, cells, virosomes, physical methods including electroporation, microinjection, osmotic lysis, nanoparticles, sonoporation to locally inject therapeutic molecules. The characteristic properties of non-viral vectors and their use for the delivery of therapeutic molecules for the diagnosis and treatment of disorders and to target tumors are also discussed. The potential of the transduced peptides and proteins was used as new therapeutic compounds against infectious diseases, to complement deficiencies in specific genes, to specifically kill tumour cells, for gene therapy. The protein delivery vectors can enhance the transfection at low concentrations and help to develop future gene delivery systems with reduced toxicity. Vitamin B12, folic acid, biotin, and riboflavin are essential in the treatment of cancer. Ultrasound has a potential in the delivery of therapeutic agents. The new developing technologies of drug delivery and targeting offer the possibility to improve the therapeutic possibilities of the existing drugs and to develop novel therapeutics. PMID:21864112

Todorova, Roumiana

2011-08-24

82

GLP-1 gene delivery for the treatment of type 2 diabetes.  

PubMed

Glucagon-like peptide-1 (GLP-1) is a potent insulinotrophic hormone, which makes GLP-1 an attractive candidate for the treatment of type 2 diabetes. However, the short plasma half-life of the active forms of GLP-1 poses an obstacle to the sustained delivery of this peptide. In this study, we evaluated the effect of GLP-1 gene delivery both in vitro and in vivo using a new plasmid constructed with a modified GLP-1 (7-37) cDNA. This cDNA contains a furin cleavage site between the start codon and the GLP-1 coding region. The expression of the GLP-1 gene was driven by a chicken beta-actin promoter (pbetaGLP1). The level of the GLP-1 mRNA was evaluated by RT-PCR 24 h after transfection. The in vitro results showed a dose-dependent expression of GLP-1. Coculture assay of the GLP-1 plasmid-transfected cells with isolated rat islet cells demonstrated that GLP-1 increased insulin secretion by twofold, compared to controls during a hyperglycemic challenge. A single injection of polyethyleneimine/pbetaGLP1 complex into ZDF rats resulted in increasing insulin secretion and decreasing blood glucose level that was maintained for 2 weeks. This GLP-1 gene delivery system may provide an effective and safe treatment modality for type 2 diabetes. PMID:12727110

Oh, Seungjoon; Lee, Minhyung; Ko, Kyung Soo; Choi, Suna; Kim, Sung Wan

2003-04-01

83

Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs  

PubMed Central

Controlled-release delivery of 6-?-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. Microneedle pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6 fold enhancement in steady state plasma concentration was observed in vivo with MN treated skin with NTXOL·HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible non-lipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application.

Banks, Stan L.; Pinninti, Raghotham R.; Gill, Harvinder S.; Paudel, Kalpana S.; Crooks, Peter A.; Brogden, Nicole K.; Prausnitz, Mark R.; Stinchcomb, Audra L.

2010-01-01

84

An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds.  

PubMed

We developed a multi-functional construct capable of controlled delivery of bioactive substances that can improve wound repair by supporting the intrinsic ability of the skin to heal. We synthesized electrospun scaffolds-composed of a blend of the degradable polymers poly(l-lactide) (PLA) or polycaprolactone (PCL)-that produce highly efficient non-viral in vivo gene delivery to cells in the wound bed, provide a protective barrier during early wound healing, and support cell migration and growth. This multi-functional material was tested for its influence on wound healing: scaffolds were loaded with plasmids encoding keratinocyte growth factor (KGF) and applied to full-thickness wounds in mice. Compared to scaffolds with control plasmids, animals receiving the KGF plasmid-loaded scaffold produced significant enhancements in wound healing, which was quantified by improvements in the rate of wound re-epithelialization, keratinocyte proliferation, and granulation response. Further, we quantified the expression level of endogenous and plasmid-derived KGF in wound samples: qRT-PCR on wound sections revealed a correlation between the levels of plasmid-derived protein expression and histological analysis of wound healing, revealing an inverse relationship between the expression level of exogenous KGF and the size of the unhealed epithelial layer in wounds. Our findings suggest that engineered nanofiber PLA/PCL scaffolds are capable of highly efficient controlled DNA delivery and are promising materials for treatment of cutaneous wounds. PMID:23453058

Kobsa, Serge; Kristofik, Nina J; Sawyer, Andrew J; Bothwell, Alfred L M; Kyriakides, Themis R; Saltzman, W Mark

2013-02-27

85

Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment  

PubMed Central

Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood–brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood–brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring.

Chen, Pin-Yuan; Liu, Hao-Li; Hua, Mu-Yi; Yang, Hung-Wei; Huang, Chiung-Yin; Chu, Po-Chun; Lyu, Lee-Ang; Tseng, I-Chou; Feng, Li-Ying; Tsai, Hong-Chieh; Chen, Shu-Mei; Lu, Yu-Jen; Wang, Jiun-Jie; Yen, Tzu-Chen; Ma, Yunn-Hwa; Wu, Tony; Chen, Jyh-Ping; Chuang, Jih-Ing; Shin, Jyh-Wei; Hsueh, Chuen; Wei, Kuo-Chen

2010-01-01

86

Dosimetric variances anticipated from breathing- induced tumor motion during tomotherapy treatment delivery  

NASA Astrophysics Data System (ADS)

In their classic paper, Yu et al (1998 Phys. Med. Biol. 43 91) investigated the interplay between tumor motion caused by breathing and dynamically collimated, intensity-modulated radiation delivery. The paper's analytic model assumed an idealized, sinusoidal pattern of motion. In this work, we investigate the effect of tumor motion based on patients' breathing patterns for typical tomotherapy treatments with field widths of 1.0 and 2.5 cm. The measured breathing patterns of 52 lung- and upper-abdominal-cancer patients were used to model a one-dimensional motion. A convolution of the measured beam-dose profiles with the motion model was used to compute the dose-distribution errors, and the positive and negative dose errors were recorded for each simulation. The dose errors increased with increasing motion magnitude, until the motion was similar in magnitude to the field width. For the 1.0 cm and 2.5 cm field widths, the maximum dose-error magnitude exceeded 10% in some simulations, even with breathing-motion magnitudes as small as 5 mm and 10 mm, respectively. Dose errors also increased slightly with increasing couch speed. We propose that the errors were due to subtle drifts in the amplitude and frequency of breathing motion, as well as changes in baseline (exhalation) position, causing both over- and under-dosing of the target. The results of this study highlight potential breathing-motion-induced dose delivery errors in tomotherapy. However, for conventionally fractionated treatments, the dose delivery errors may not be co-located and may average out over many fractions, although this may not be true for hypofractionated treatments.

Chaudhari, S. R.; Goddu, S. M.; Rangaraj, D.; Pechenaya, O. L.; Lu, W.; Kintzel, E.; Malinowski, K.; Parikh, P. J.; Bradley, J. D.; Low, D. A.

2009-04-01

87

Aerosol-based efficient delivery of azithromycin to alveolar macrophages for treatment of respiratory infections.  

PubMed

The efficacy of aerosol-based delivery of azithromycin (AZM) for the treatment of respiratory infections caused by pathogenic microorganisms infected in alveolar macrophages (AMs) was evaluated by comparison with oral administration. The aerosol formulation of AZM (0.2?mg/kg) was administered to rat lungs using a Liquid MicroSprayer(®). The oral formulation of AZM (50?mg/kg) was used for comparison. Time-courses of concentrations of AZM in AMs following administration were obtained, and then the therapeutic availability (TA) was calculated. In addition, the area under the concentrations of AZM in AMs - time curve/minimum inhibitory concentration at which 90% of isolates ratio (AUC/MIC90) were calculated to estimate the antibacterial effects in AMs. The TA of AZM in AMs following administration of aerosol formulation was markedly greater than that following administration of oral formulation. In addition, the AUC/MIC90 of AZM in AMs was markedly higher than the effective values. This indicates that the aerosol formulation could be useful for the treatment of respiratory infections caused by pathogenic microorganisms infected in AMs. This study suggests that aerosolized AZM is an effective pulmonary drug delivery system for the treatment of respiratory infections. PMID:22812381

Togami, Kohei; Chono, Sumio; Morimoto, Kazuhiro

2012-07-20

88

Evaluating intra-articular drug delivery for the treatment of osteoarthritis in a rat model.  

PubMed

Osteoarthritis (OA) is a degenerative joint disease that can result in joint pain, loss of joint function, and deleterious effects on activity levels and lifestyle habits. Current therapies for OA are largely aimed at symptomatic relief and may have limited effects on the underlying cascade of joint degradation. Local drug delivery strategies may provide for the development of more successful OA treatment outcomes that have potential to reduce local joint inflammation, reduce joint destruction, offer pain relief, and restore patient activity levels and joint function. As increasing interest turns toward intra-articular drug delivery routes, parallel interest has emerged in evaluating drug biodistribution, safety, and efficacy in preclinical models. Rodent models provide major advantages for the development of drug delivery strategies, chiefly because of lower cost, successful replication of human OA-like characteristics, rapid disease development, and small joint volumes that enable use of lower total drug amounts during protocol development. These models, however, also offer the potential to investigate the therapeutic effects of local drug therapy on animal behavior, including pain sensitivity thresholds and locomotion characteristics. Herein, we describe a translational paradigm for the evaluation of an intra-articular drug delivery strategy in a rat OA model. This model, a rat interleukin-1beta overexpression model, offers the ability to evaluate anti-interleukin-1 therapeutics for drug biodistribution, activity, and safety as well as the therapeutic relief of disease symptoms. Once the action against interleukin-1 is confirmed in vivo, the newly developed anti-inflammatory drug can be evaluated for evidence of disease-modifying effects in more complex preclinical models. PMID:19943805

Allen, Kyle D; Adams, Samuel B; Setton, Lori A

2010-02-01

89

Treatment Planning to Improve Delivery Accuracy and Patient Throughput in Helical Tomotherapy  

SciTech Connect

Purpose: To investigate delivery quality assurance (DQA) discrepancies observed for a subset of helical tomotherapy patients. Methods and Materials: Six tomotherapy patient plans were selected for analysis. Three had passing DQA ion chamber (IC) measurements, whereas 3 had measurements deviating from the expected dose by more than 3.0%. All plans used similar parameters, including: 2.5 cm field-width, 15-s gantry period, and pitch values ranging from 0.143 to 0.215. Preliminary analysis suggested discrepancies were associated with plans having predominantly small leaf open times (LOTs). To test this, patients with failing DQA measurements were replanned using an increased pitch of 0.287. New DQA plans were generated and IC measurements performed. Exit fluence data were also collected during DQA delivery for dose reconstruction purposes. Results: Sinogram analysis showed increases in mean LOTs ranging from 29.8% to 83.1% for the increased pitch replans. IC measurements for these plans showed a reduction in dose discrepancies, bringing all measurements within {+-}3.0%. The replans were also more efficient to deliver, resulting in reduced treatment times. Dose reconstruction results were in excellent agreement with IC measurements, illustrating the impact of leaf-timing inaccuracies on plans having predominantly small LOTs. Conclusions: The impact of leaf-timing inaccuracies on plans with small mean LOTs can be considerable. These inaccuracies result from deviations in multileaf collimator latency from the linear approximation used by the treatment planning system and can be important for plans having a 15-s gantry period. The ability to reduce this effect while improving delivery efficiency by increasing the pitch is demonstrated.

Westerly, David C. [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States)], E-mail: westerly@wisc.edu; Soisson, Emilie [Department of Human Oncology, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Chen Quan [Department of TomoTherapy, Inc., Madison, WI (United States); Woch, Katherine [Department of Human Oncology, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Schubert, Leah [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Olivera, Gustavo [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Department of TomoTherapy, Inc., Madison, WI (United States); Mackie, Thomas R. [Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Department of Human Oncology, University of Wisconsin, School of Medicine and Public Health, Madison, WI (United States); Department of TomoTherapy, Inc., Madison, WI (United States)

2009-07-15

90

Treatment planning to improve delivery accuracy and patient throughput in helical tomotherapy  

PubMed Central

Purpose To investigate delivery quality assurance (DQA) discrepancies observed for a subset of helical tomotherapy patients. Methods and Materials Six tomotherapy patient plans were selected for analysis. Three had passing DQA ion chamber (IC) measurements while three had measurements deviating from the expected dose by more than 3.0%. All plans utilized similar parameters, including: 2.5 cm field-width, 15 s gantry period, and pitch values ranging from 0.143–0.215. Preliminary analysis suggested discrepancies were associated with plans having predominantly small leaf open times (LOTs). To test this, patients with failing DQA measurements were replanned using an increased pitch of 0.287. New DQA plans were generated and IC measurements performed. Exit fluence data was also collected during DQA delivery for dose reconstruction purposes. Results Sinogram analysis showed increases in mean LOTs ranging from 29.8–83.1% for the increased pitch replans. IC measurements for these plans showed a reduction in dose discrepancies, bringing all measurements within ±3.0%. The replans were also more efficient to deliver, resulting in reduced treatment times. Dose reconstruction results were in excellent agreement with IC measurements, illustrating the impact of leaf-timing inaccuracies on plans having predominantly small LOTs. Conclusions The impact of leaf-timing inaccuracies on plans with small mean LOTs can be considerable. These inaccuracies result from deviations in MLC leaf latency from the linear approximation used by the treatment planning system and can be important for plans having a 15 s gantry period. The ability to reduce this effect while improving delivery efficiency by increasing the pitch is demonstrated.

Westerly, David C.; Soisson, Emilie; Chen, Quan; Woch, Katherine; Schubert, Leah; Olivera, Gustavo; Mackie, Thomas R.

2009-01-01

91

Assessing fidelity of treatment delivery in group and individual 12-step facilitation.  

PubMed

Twelve step facilitation (TSF) is an emerging, empirically supported treatment, the study of which will be strengthened by rigorous fidelity assessment. This report describes the development, reliability and concurrent validity of the Twelve Step Facilitation Adherence Competence Empathy Scale (TSF ACES), a comprehensive fidelity rating scale for group and individual TSF treatment developed for the National Drug Abuse Treatment Clinical Trials Network study, Stimulant Abuser Groups to Engage in 12-Step. Independent raters used TSF ACES to rate treatment delivery fidelity of 966 (97% of total) TSF group and individual sessions. TSF ACES summary measures assessed therapist treatment adherence, competence, proscribed behaviors, empathy and overall session performance. TSF ACES showed fair to good overall reliability; weighted kappa coefficients for 59 co-rated sessions ranged from .31 to 1.00, with a mean of .69. Reliability ratings for session summary measures were good to excellent (.69-.91). Internal consistency for the instrument was variable (.47-.71). Relationships of the TSF ACES summary measures with each other, as well as relationships of the summary measures with a measure of therapeutic alliance provided support for concurrent and convergent validity. Implications and future directions for the use of TSF ACES in clinical trials and community treatment implementation are discussed. PMID:22944595

Campbell, Barbara K; Manuel, Jennifer K; Manser, Sarah Turcotte; Peavy, K Michelle; Stelmokas, Julija; McCarty, Dennis; Guydish, Joseph R

2012-09-01

92

Chronotherapeutics--a chronopharmaceutical approach to drug delivery in the treatment of asthma.  

PubMed

Bronchial asthma is a chronic inflammatory disorder of the airways associated with airflow obstruction that is reversible spontaneously or with treatment. Bronchial asthma is a disease based on established circadian rhythm. The symptoms of asthma worsen during midnight to early morning and therefore it is required to deliver the drug in such fashion that effective treatment can be obtained during the time of asthma attacks. Chronotherapy is an approach that fulfills the criteria of drug delivery at a specific time as per the pathophysiological need of the disease, to improve patient compliance. The current article focuses on the chronotherapy of bronchial asthma, methodologies involved for the existing systems, recent updates and different chronopharmaceutical technologies currently available in the market. Chronotherapy with different categories of bronchial asthma medications also has been reviewed. PMID:23022979

Nainwal, Nidhi

2012-09-27

93

The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors  

Microsoft Academic Search

Our laboratories have been working together in close collaboration for over 10 years concerning the design and performance of lipid-based drug delivery systems. Over the past 3 years we have conceived of, developed, and tested pre-clinically, a new liposome-based temperature-sensitive drug delivery system for the treatment of solid tumors. This work is reported in a series of four publications: ‘J.

David Needham; Mark W Dewhirst

2001-01-01

94

Energy modulated electron therapy: Design, implementation, and evaluation of a novel method of treatment planning and delivery  

Microsoft Academic Search

Energy modulated electron therapy (EMET) is a promising treatment modality that has the fundamental capabilities to enhance the treatment planning and delivery of superficially located targets. Although it offers advantages over x-ray intensity modulated radiation therapy (IMRT), EMET has not been widely implemented to the same level of accuracy, automation, and clinical routine as its x-ray counterpart. This lack of

Khalid Al-Yahya

2007-01-01

95

Therapist predictors of treatment delivery fidelity in a community-based trial of 12-step facilitation.  

PubMed

Abstract Background and aims: Therapist characteristics may be associated with variation in consistency, quality and effectiveness of treatment delivery. We examined associations between treatment fidelity and therapist education, experience, treatment orientation and perceived skills in a randomized, multi-site trial of Twelve Step Facilitation (TSF). Methods: Raters scored audio-recorded, TSF sessions (n?=?966; 97% of TSF sessions) from 32 community-based, trained therapists for adherence, competence, empathy and global session performance. Results: Therapists with graduate degrees had significantly higher adherence and global performance fidelity ratings. Therapists reporting more positive attitudes toward 12-Step groups had lower adherence ratings. Being in recovery was associated with lower fidelity in univariate tests, but higher adherence in multivariate analysis. Fidelity was higher for therapists reporting self-efficacy in basic counseling skills and lower for self-efficacy in addiction-specific counseling skills. Fidelity was also superior in group relative to individual TSF sessions. Conclusions: Results have implications for therapist selection, training and supervision in community-based, effectiveness trials and community implementation of evidence-based treatments. To obtain high fidelity and improve outcomes, it may be preferable to choose masters level therapists who are open to learning new treatments and have good, general counseling skills. PMID:23837717

Campbell, Barbara K; Buti, Allison; Fussell, Holly E; Srikanth, Priya; McCarty, Dennis; Guydish, Joseph R

2013-07-09

96

Increased caseloads in methadone treatment programs: Implications for the delivery of services and retention in treatment  

Microsoft Academic Search

Changes in caseload and in the provision of counseling and comprehensive services were examined among 27 outpatient methadone programs across England between 1995 and 1999. The number of patients treated at the programs doubled during this time and average waiting times increased. More patients presented for treatment with alcohol and stimulant problems, dual diagnosis, and involvement in the Criminal Justice

Duncan Stewart; Michael Gossop; John Marsden

2004-01-01

97

PEGylated estradiol benzoate liposomes as a potential local vascular delivery system for treatment of restenosis.  

PubMed

This study was directed towards the preparation and optimization of PEGylated (PEG, poly(ethylene glycol)) estradiol benzoate (ESB)-loaded liposomes to be used for the treatment of restenosis by local vascular delivery. Various liposomal formulations were prepared by thin film hydration method followed by sonication. Response surface methodology was applied to study the influence of three different independent variables, on the response of entrapment efficiency (%EE). Liposomes were characterized in terms of size, zeta potential, %EE and release profile. Incorporation of ESB was higher in egg phosphatidylcholine (EPC) liposomes, whereas the drug was displaced from liposomes, as the cholesterol (Chol) content of liposome increased. The optimum formulation composed of EPC/dioleyloxy trimethylammonium propane/distearoylphosphatidylethanolamine-PEG2000 with a molar proportion of 8.5:1:0.5 had the highest EE. In vivo studies in the balloon-injured rat carotid arteries revealed the potential of ESB-loaded liposomes as efficient local and controlled drug delivery systems to reduce restenosis. PMID:22047547

Haeri, Azadeh; Sadeghian, Saeed; Rabbani, Shahram; Anvari, Maryam Sotoudeh; Erfan, Mohammad; Dadashzadeh, Simin

2011-11-02

98

Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems  

PubMed Central

Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease(AD), are a group of pathologies characterized by a progressive and specific loss of certain brain cell populations. Oxidative stress, mitochondrial dysfunction, and apoptosis play interrelated roles in these disorders. It is well documented that free radical oxidative damage, particularly on neuronal lipids, proteins, DNA, and RNA, is extensive in PD and AD brains. Moreover, alterations of glutathione (GSH) metabolism in brain have been implicated in oxidative stress and neurodegenerative diseases. As a consequence, the reduced GSH levels observed in these pathologies have stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. Unfortunately, GSH delivery to the central nervous system (CNS) is limited due to a poor stability and low bioavailability. Medicinal-chemistry- and technology-based approaches are commonly used to improve physicochemical, biopharmaceutical, and drug delivery properties of therapeutic agents. This paper will focus primarily on these approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases. Here, we discuss the beneficial properties of these approaches and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically from PD and AD.

Cacciatore, Ivana; Baldassarre, Leonardo; Fornasari, Erika; Mollica, Adriano; Pinnen, Francesco

2012-01-01

99

Glucagon-like peptide-1 plasmid construction and delivery for the treatment of type 2 diabetes.  

PubMed

Glucagon-like peptide-1 (GLP-1) is a 30-amino-acid hormone produced by intestinal L cells. It has been proposed that GLP-1 can be used as a new treatment for type 2 diabetes mellitus because it acts to augment insulin secretion and its effectiveness is maintained in type 2 diabetic patients. Despite its many remarkable advantages as a therapeutic agent for diabetes, GLP-1 is not immediately clinically applicable because of its extremely short half-life. One way to overcome this drawback is GLP1 gene delivery, which enables GLP-1 production in the body. In this study, the effect of GLP1 gene delivery was evaluated both in vitro and in vivo using a new plasmid constructed with a GLP1 (7-37) cDNA. The expression of the GLP1 gene was driven by a SV40 promoter/enhancer. To increase the expression level of GLP-1, nuclear factor kappaB binding sites were introduced. The in vitro results showed expression of GLP-1 and in vitro activity of GLP-1, which is a glucose-dependent insulinotropic action. A single systemic administration of polyethyleneimine/pSIGLP1NFkappaB complex into DIO mice resulted in increasing insulin secretion and decreasing blood glucose levels for a duration longer than 2 weeks. PMID:16039908

Choi, Suna; Oh, Seungjoon; Lee, Minhyung; Kim, Sung Wan

2005-07-21

100

Pulmonary delivery of cisplatin-hyaluronan conjugates via endotracheal instillation for the treatment of lung cancer  

PubMed Central

Cisplatin (CDDP) intravenous treatments suffer several dose-limiting toxicity issues. Hyaluronan (HA), a naturally occurring biopolymer in the interstitium, is primarily cleared by the lymphatic system. An alteration in input rate and administration route through pulmonary delivery of hyaluronan-cisplatin conjugate (HA-Pt) may increase local lung CDDP concentrations and decrease systemic toxicity. Sprague-Dawley rats were split into four groups: i.v. CDDP (3.5 mg/kg), i.v. HA-Pt conjugate (3.5 mg/kg equivalent CDDP), lung instillation CDDP and lung instillation HA-Pt conjugate. Total platinum level in the lungs of the HA-Pt lung instillation group was 5.7-fold and 1.2-fold higher than the CDDP intravenous group at 24 h and 96 h, respectively. A 1.1-fold increase of Pt accumulation in lung draining nodes for the HA-Pt lung instillation group was achieved at 24 h relative to the CDDP i.v. group. In the brain and kidneys, the CDDP i.v. group had higher tissue/plasma ratios compared to the HA-Pt lung instillation group. Augmented tissue distribution from CDDP i.v. could translate into enhanced tissue toxicity compared to the altered input rate and distribution of the intrapulmonary nanoformulation. In conclusion, a local pulmonary CDDP delivery system was developed with increased platinum concentration in the lungs and draining nodes compared to i.v. therapy.

Xie, Yumei; Aillon, Kristin L.; Cai, Shuang; Christian, Jason M.; Davies, Neal M.; Berkland, Cory J.; Forrest, M. Laird

2010-01-01

101

TREATMENT Validation of a Scale for Rating the Delivery of PsychoSocial Treatments for Alcohol Dependence and Misuse: The UKATT Process Rating Scale (PRS)  

Microsoft Academic Search

Aim: The aim of this study was to describe the development and validation of the UK Alcohol Treatment Trial Process Rating Scale (UKATT PRS), a manual based method for monitoring and rating the delivery of psychosocial treatments of alcohol dependence and misuse. Methods: Following adaptation and further development of a validated rating scale, the ability of the UKATT PRS to

Gillian Tober; Wendy Clyne; Olwyn Finnegan; Amanda Farrin; Ian Russell

102

Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer.  

PubMed

Camptothecins are a family of alkaloids originally extracted from the Chinese tree Camptotheca acuminata, Nyssaceae, exhibiting a strong activity against colorectal cancer (CRC). CRC is a common malignancy worlwide. Despite significant developments in the treatment of this disease, it still causes considerable morbidity and mortality. Recent advances include both newer cytotoxic chemotherapies and novel biological agents including the more hydrosoluble camptothecin derivative, namely irinotecan. Camptothecin and irinotecan are selective human topoisomerase I inhibitors but their application for curing CRC is compromised by their intrinsic high toxicity, insolubility and instability. Furthermore, pharmacology studies have determined that continuously and prolonged schedules of administration are required. The aim of this work is to review the state of the art of camptothecin and its derivative irinotecan's delivery methods. PMID:22283650

Mollica, Adriano; Stefanucci, Azzurra; Feliciani, Federica; Cacciatore, Ivana; Cornacchia, Catia; Pinnen, Francesco

2012-03-01

103

Is community treatment best? a randomised trial comparing delivery of cancer treatment in the hospital, home and GP surgery.  

PubMed

Background:Care closer to home is being explored as a means of improving patient experience as well as efficiency in terms of cost savings. Evidence that community cancer services improve care quality and/or generate cost savings is currently limited. A randomised study was undertaken to compare delivery of cancer treatment in the hospital with two different community settings.Methods:Ninety-seven patients being offered outpatient-based cancer treatment were randomised to treatment delivered in a hospital day unit, at the patient's home or in local general practice (GP) surgeries. The primary outcome was patient-perceived benefits, using the emotional function domain of the EORTC quality of life (QOL) QLQC30 questionnaire evaluated after 12 weeks. Secondary outcomes included additional QOL measures, patient satisfaction, safety and health economics.Results:There was no statistically significant QOL difference between treatment in the combined community locations relative to hospital (difference of -7.2, 95% confidence interval: -19·5 to +5·2, P=0.25). There was a significant difference between the two community locations in favour of home (+15·2, 1·3 to 29·1, P=0.033). Hospital anxiety and depression scale scores were consistent with the primary outcome measure. There was no evidence that community treatment compromised patient safety and no significant difference between treatment arms in terms of overall costs or Quality Adjusted Life Year. Seventy-eight percent of patients expressed satisfaction with their treatment whatever their location, whereas 57% of patients preferred future treatment to continue at the hospital, 81% at GP surgeries and 90% at home. Although initial pre-trial interviews revealed concerns among health-care professionals and some patients regarding community treatment, opinions were largely more favourable in post-trial interviews.Interpretation:Patient QOL favours delivering cancer treatment in the home rather than GP surgeries. Nevertheless, both community settings were acceptable to and preferred by patients compared with hospital, were safe, with no detrimental impact on overall health-care costs. PMID:23989945

Corrie, P G; Moody, A M; Armstrong, G; Nolasco, S; Lao-Sirieix, S-H; Bavister, L; Prevost, A T; Parker, R; Sabes-Figuera, R; McCrone, P; Balsdon, H; McKinnon, K; Hounsell, A; O'Sullivan, B; Barclay, S

2013-08-29

104

Is community treatment best? a randomised trial comparing delivery of cancer treatment in the hospital, home and GP surgery  

PubMed Central

Background: Care closer to home is being explored as a means of improving patient experience as well as efficiency in terms of cost savings. Evidence that community cancer services improve care quality and/or generate cost savings is currently limited. A randomised study was undertaken to compare delivery of cancer treatment in the hospital with two different community settings. Methods: Ninety-seven patients being offered outpatient-based cancer treatment were randomised to treatment delivered in a hospital day unit, at the patient's home or in local general practice (GP) surgeries. The primary outcome was patient-perceived benefits, using the emotional function domain of the EORTC quality of life (QOL) QLQC30 questionnaire evaluated after 12 weeks. Secondary outcomes included additional QOL measures, patient satisfaction, safety and health economics. Results: There was no statistically significant QOL difference between treatment in the combined community locations relative to hospital (difference of ?7.2, 95% confidence interval: ?19·5 to +5·2, P=0.25). There was a significant difference between the two community locations in favour of home (+15·2, 1·3 to 29·1, P=0.033). Hospital anxiety and depression scale scores were consistent with the primary outcome measure. There was no evidence that community treatment compromised patient safety and no significant difference between treatment arms in terms of overall costs or Quality Adjusted Life Year. Seventy-eight percent of patients expressed satisfaction with their treatment whatever their location, whereas 57% of patients preferred future treatment to continue at the hospital, 81% at GP surgeries and 90% at home. Although initial pre-trial interviews revealed concerns among health-care professionals and some patients regarding community treatment, opinions were largely more favourable in post-trial interviews. Interpretation: Patient QOL favours delivering cancer treatment in the home rather than GP surgeries. Nevertheless, both community settings were acceptable to and preferred by patients compared with hospital, were safe, with no detrimental impact on overall health-care costs.

Corrie, P G; Moody, A M; Armstrong, G; Nolasco, S; Lao-Sirieix, S-H; Bavister, L; Prevost, A T; Parker, R; Sabes-Figuera, R; McCrone, P; Balsdon, H; McKinnon, K; Hounsell, A; O'Sullivan, B; Barclay, S

2013-01-01

105

Combinational Spinal GAD65 Gene Delivery and Systemic GABA-Mimetic Treatment for Modulation of Spasticity  

PubMed Central

Background Loss of GABA-mediated pre-synaptic inhibition after spinal injury plays a key role in the progressive increase in spinal reflexes and the appearance of spasticity. Clinical studies show that the use of baclofen (GABAB receptor agonist), while effective in modulating spasticity is associated with major side effects such as general sedation and progressive tolerance development. The goal of the present study was to assess if a combined therapy composed of spinal segment-specific upregulation of GAD65 (glutamate decarboxylase) gene once combined with systemic treatment with tiagabine (GABA uptake inhibitor) will lead to an antispasticity effect and whether such an effect will only be present in GAD65 gene over-expressing spinal segments. Methods/Principal Findings Adult Sprague-Dawley (SD) rats were exposed to transient spinal ischemia (10 min) to induce muscle spasticity. Animals then received lumbar injection of HIV1-CMV-GAD65 lentivirus (LVs) targeting ventral ?-motoneuronal pools. At 2–3 weeks after lentivirus delivery animals were treated systemically with tiagabine (4, 10, 20 or 40 mg/kg or vehicle) and the degree of spasticity response measured. In a separate experiment the expression of GAD65 gene after spinal parenchymal delivery of GAD65-lentivirus in naive minipigs was studied. Spastic SD rats receiving spinal injections of the GAD65 gene and treated with systemic tiagabine showed potent and tiagabine-dose-dependent alleviation of spasticity. Neither treatment alone (i.e., GAD65-LVs injection only or tiagabine treatment only) had any significant antispasticity effect nor had any detectable side effect. Measured antispasticity effect correlated with increase in spinal parenchymal GABA synthesis and was restricted to spinal segments overexpressing GAD65 gene. Conclusions/Significance These data show that treatment with orally bioavailable GABA-mimetic drugs if combined with spinal-segment-specific GAD65 gene overexpression can represent a novel and highly effective anti-spasticity treatment which is associated with minimal side effects and is restricted to GAD65-gene over-expressing spinal segments.

Kakinohana, Osamu; Hefferan, Michael P.; Miyanohara, Atsushi; Nejime, Tetsuya; Marsala, Silvia; Juhas, Stefan; Juhasova, Jana; Motlik, Jan; Kucharova, Karolina; Strnadel, Jan; Platoshyn, Oleksandr; Lazar, Peter; Galik, Jan; Vinay, Laurent; Marsala, Martin

2012-01-01

106

Advances in the psychosocial treatment of addiction: the role of technology in the delivery of evidence-based psychosocial treatment.  

PubMed

The clinical community has a growing array of psychosocial interventions with a strong evidence base available for the treatment of SUDs. Considerable opportunity exists for leveraging technology in the delivery of evidence-based interventions to promote widespread reach and impact of evidence-based care. Data from this line of research to date are promising, and underscore the potential public health impact of technology-based therapeutic tools. To fully realize the potential of technology-delivered interventions, several areas of inquiry remain important. First, scientifically sound strategies should be explored to ensure technology-based interventions are optimally designed to produce maximal behavior change. Second, efficient and effective methods should be identified to integrate technology-based interventions into systems of care in a manner that is most responsive to the needs of individual users. Third, payment, privacy, and regulatory systems should be refined and extended to go beyond electronic medical records and telehealth/distance care models, and support the deployment of technology-based systems to enhance the quality, efficiency and cost-effectiveness of care. Fourth, the mechanisms underlying behavior change derived from technology-based treatments should be explicated, including new mechanisms that may be tapped via novel, technology-based tools. Such work will be critical in isolating mechanisms that are useful in predicting treatment response, and in ensuring that key ingredients are present in technology-based interventions as they are made widely available. PMID:22640767

Marsch, Lisa A; Dallery, Jesse

2012-04-11

107

Increased caseloads in methadone treatment programs: implications for the delivery of services and retention in treatment.  

PubMed

Changes in caseload and in the provision of counseling and comprehensive services were examined among 27 outpatient methadone programs across England between 1995 and 1999. The number of patients treated at the programs doubled during this time and average waiting times increased. More patients presented for treatment with alcohol and stimulant problems, dual diagnosis, and involvement in the Criminal Justice System. Provision of individual counseling and comprehensive services was high at both points, although services for family/relationship problems were reduced at followup. Changes were reported in disciplinary procedures. Drug positive urine tests were more likely to result in loss of patient privileges, and there was a significant increase in discharges for breaking program rules, missing appointments, and consuming alcohol. The study allows only tentative conclusions to be drawn, but these changes may be indicative of increased pressures placed on the programs and their staff. PMID:15610831

Stewart, Duncan; Gossop, Michael; Marsden, John

2004-12-01

108

Long term impact of large scale community-directed delivery of doxycycline for the treatment of onchocerciasis  

PubMed Central

Background Anti-Wolbachia treatment with doxycycline is effective in sterilising and killing adult Onchocerca volvulus nematodes, proving superior to ivermectin and of great potential as an alternative approach for the treatment and control of onchocerciasis, particularly in areas of Loa loa co-endemicity. Nevertheless, the length of the required treatment poses potential logistical problems and risk of poor compliance, raising a barrier to the use of doxycycline in Mass Drug Administration (MDA) strategies. In 2007 and 2008 a feasibility trial of community-directed treatment with doxycycline was carried out in two health districts in Cameroon, co-endemic for O. volvulus and L. loa. With 17,519 eligible subjects, the therapeutic coverage was 73.8% with 97.5% compliance, encouraging the feasibility of using doxycycline community-directed delivery in restricted populations of this size. The current study evaluated the effectiveness of this community-directed delivery of doxycycline four years after delivery. Findings Infection with O. volvulus was evaluated by skin biopsy and nodule palpation. Of the 507 subjects recruited, 375 had completed the treatment with doxycycline followed by one or two rounds of annual ivermectin MDA and 132 received one or two rounds of annual ivermectin MDA alone. Statistically significant lower microfilarial prevalence (17.0% [doxycycline plus ivermectin group], 27.0% [ivermectin only group], p = 0.014) and load (p = 0.012) were found in people that had received doxycycline followed by ivermectin compared to those who received ivermectin only. Conclusions This study demonstrates the long-term effectiveness of doxycycline treatment delivered with a community-directed strategy even when evaluated four years after delivery in an area of ongoing transmission. This finding shows that a multi-week course of treatment is not a barrier to community-delivery of MDA in restricted populations of this size and supports its implementation to compliment existing control strategies for onchocerciasis, where needed.

2012-01-01

109

Innovative delivery systems for migraine: the clinical utility of a transdermal patch for the acute treatment of migraine.  

PubMed

Migraine is a disabling, painful primary headache disorder that is associated with various combinations of neurological, gastrointestinal, autonomic and pain symptoms. Gastrointestinal disturbances associated with migraine, including nausea and vomiting, affect a majority of migraineurs and often result in a delay in taking or avoidance of pharmacological intervention. Gastric stasis and vomiting may lead to delayed or inconsistent absorption of orally administered medications. Many migraineurs awake early in the morning with their attack progressing and already associated with nausea and vomiting. As a result, there is a need for a novel, non-invasive, non-oral delivery system for fast and effective acute treatment of migraine. There are two non-oral delivery systems currently available in the US for the acute treatment of migraine: three nasal sprays and two injectable formulations. Although nasal sprays depend partially on nasal mucosal absorption, a significant amount of drug is swallowed, transits the stomach and is absorbed in the small intestine, which is not as rapid or effective a route of delivery for those migraineurs with gastric stasis. Sumatriptan is rapidly absorbed by subcutaneous injection with or without a needle, but the invasiveness and discomfort of the delivery, the high incidence of adverse events and the high recurrence rate all limit its use for many patients. Iontophoretic delivery of medication is a non-invasive transdermal approach that uses small amounts of electrical current to promote rapid movement of the ionized drug through the skin and into the systemic circulation. This delivery bypasses hepatic first-pass metabolism and also avoids gastric transit delay and slowing of small intestinal absorption associated with gastrointestinal stasis in migraineurs. Two pharmacokinetic studies have demonstrated that iontophoretic transdermal delivery of sumatriptan results in rapid and consistent achievement of therapeutic plasma concentrations. These studies also suggest that, by avoiding patient exposure to a rapid rise in and high plasma concentrations of sumatriptan as seen with injectable sumatriptan, transdermal delivery using iontophoresis may significantly reduce typical triptan-related adverse events. A large, randomized, double-blind, placebo-controlled, multicentre clinical trial showed statistically significant efficacy, good tolerability and virtually no triptan-related adverse events. Iontophoretic delivery of sumatriptan, with a novel transdermal patch device, offers patients a migraine-specific medication that is non-invasive and non-oral. Clinically, transdermal delivery provides rapid and effective relief of migraine while bypassing the gastrointestinal tract, with minimal classic triptan-related adverse effects. This unique approach facilitates the rapid absorption of this migraine-specific triptan, which should improve the chances of consistently achieving a therapeutic plasma concentration of sumatriptan, resulting in effective migraine relief. PMID:20932065

Rapoport, Alan M; Freitag, Fred; Pearlman, Starr H

2010-11-01

110

Constant dopaminergic stimulation by transdermal delivery of dopaminergic drugs: a new treatment paradigm in Parkinson's disease.  

PubMed

Current dopaminergic therapies for the treatment of Parkinson's disease are associated with the development of long-term motor complications. Abnormal pulsatile stimulation of dopamine receptors is thought to underlie the development of motor complications. There is thus a need for therapies that mimic the normal physiological state more closely by resulting in constant dopaminergic stimulation (CDS). Several studies support the hypothesis that CDS can reverse levodopa-induced motor complications. Other potential benefits of CDS include alleviating nocturnal disturbances, minimizing daytime sleepiness, avoiding priming for motor fluctuations and dyskinesia, preventing the development of gastrointestinal dysfunction and reducing the risk of developing psychosis or behavioural disturbances. Continuous infusion of dopaminergic therapies is impractical for the routine treatment of large numbers of patients. Although catechol-O-methyltransferase inhibitors or sustained-release preparations of levodopa may be beneficial, they do not entirely eliminate pulsatile stimulation of dopamine receptors. A new dopamine agonist (rotigotine), delivered over 24 h by a once-daily transdermal patch, has been investigated in several clinical trials. Continuous delivery of rotigotine has been shown to provide 'true' CDS in animal models. The potential of true CDS therapy to prevent or reduce long-term motor and non-motor complications requires investigation in appropriately designed clinical trials. PMID:18042245

Steiger, M

2007-11-27

111

Treatment planning and delivery in neutron radiotherapy of soft tissue sarcomas.  

PubMed

Well differentiated soft tissue sarcomas may benefit from fast neutron radiotherapy, in particular inoperable and recurrent tumors and tumors with residual disease after non-radical surgery. Treatment planning in a multidisciplinary pretherapeutic approach has to be based on tumor size and site and histopathology. Target volume definitions for potential microscopic spread and for the high risk region of local recurrence have to consider the preoperative tumor localization (imaging), the biological behavior and the extent of surgery. GI/II, T1-3 tumors after intralesional or marginal resection are indications for neutron therapy. Treatment planning and delivery has to take into account the narrow therapeutic range of fast neutrons and include individual immobilization devices, manufacturing of bolus and CT based computed dose calculations. Neutron radiotherapy techniques at the d, T generator are comparable to photon techniques except individual beam shaping, field size and portal verification. Total dose is 16 Gy neutrons in the high risk region and 12 to 13 Gy in the region of potential microscopic spread. PMID:2105534

Pötter, R; Knocke, T H; Haverkamp, U; Al-Dandashi, C

1990-01-01

112

Pharmacological and non pharmacological treatment for relief of perineal pain after vaginal delivery Tratamento farmacológico e não farmacológico no alívio da dor perineal pós-parto normal  

Microsoft Academic Search

Objective: To identify the types of pharmacological and non- pharmacological treatments used during hospitalization, in the relief of perineal pain after vaginal deliveries. Methods: Data were obtained from medical files of patients who had vaginal deliveries during 2007. results: The mean age of mothers was 32.4 years, and 97.7% of them suffered perineal trauma. As to treatment for relief of

Joyce Hasegawa; Lucila Coca Leventhal

113

Tratamento farmacológico e não farmacológico no alívio da dor perineal pós-parto normal Pharmacological and non pharmacological treatment for relief of perineal pain after vaginal delivery  

Microsoft Academic Search

objective: To identify the types of pharmacological and non- pharmacological treatments used during hospitalization, in the relief of perineal pain after vaginal deliveries. Methods: Data were obtained from medical files of patients who had vaginal deliveries during 2007. results: The mean age of mothers was 32.4 years, and 97.7% of them suffered perineal trauma. As to treatment for relief of

Joyce Hasegawa; Lucila Coca Leventhal

114

A biodegradable antibiotic delivery system based on poly-(trimethylene carbonate) for the treatment of osteomyelitis  

PubMed Central

Background and purpose Many investigations on biodegradable materials acting as an antibiotic carrier for local drug delivery are based on poly(lactide). However, the use of poly(lactide) implants in bone has been disputed because of poor bone regeneration at the site of implantation. Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polymer that does not produce acidic degradation products. We explored the suitability of PTMC as an antibiotic releasing polymer for the local treatment of osteomyelitis. Methods This study addressed 2 separate attributes of PTMC: (1) the release kinetics of gentamicin-loaded PTMC and (2) its behavior in inhibiting biofilm formation. Both of these characteristics were compared with those of commercially available gentamicin-loaded poly(methylmethacrylate) (PMMA) beads, which are commonly used in the local treatment of osteomyelitis. Results In a lipase solution that mimics the in vivo situation, PTMC discs with gentamicin incorporated were degraded by surface erosion and released 60% of the gentamicin within 14 days. This is similar to the gentamicin release from clinically used PMMA beads. Moreover, biofilm formation by Staphylococcus aureus was inhibited by approximately 80% over at least 14 days in the presence of gentamicin-loaded PTMC discs. This is similar to the effect of gentamicin-loaded PMMA beads. In the absence of the lipase, surface erosion of PTMC discs did not occur and gentamicin release and biofilm inhibition were limited. Interpretation Since gentamicin-loaded PTMC discs show antibiotic release characteristics and biofilm inhibition characteristics similar to those of gentamicin-loaded PMMA beads, PTMC appears to be a promising biodegradable carrier in the local treatment of osteomyelitis.

2009-01-01

115

Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria.  

PubMed

In the context of an Intermittent preventive treatment (IPTp) trial for pregnant women in Malawi, Plasmodium falciparum samples from 85 women at enrollment and 35 women at delivery were genotyped for mutations associated with sulfadoxine-pyrimethamine resistance. The prevalence of the highly resistant haplotype with mutations at codons 51 and 108 of dihydrofolate reductase (dhfr) and codons 437 and 540 of dihydropteroate synthase (dhps) increased from 81% at enrollment to 100% at delivery (P = 0.01). Pregnant women who were smear-positive at enrollment were more likely to have P. falciparum parasitemia at delivery. These results lend support to concerns that IPTp use may lead to increased drug resistance in pregnant women during pregnancy and emphasise the importance of screening pregnant women for malaria parasites in areas with prevalent SP resistance even when they are already on IPTp. PMID:23198734

Lin, Jessica T; Mbewe, Bernard; Taylor, Steve M; Luntamo, Mari; Meshnick, Steven R; Ashorn, Per

2012-11-30

116

A new era of cancer treatment: carbon nanotubes as drug delivery tools  

PubMed Central

Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology.

Madani, Seyed Yazdan; Naderi, Naghmeh; Dissanayake, Oshani; Tan, Aaron; Seifalian, Alexander M

2011-01-01

117

Nanoparticulate delivery of LHRH analogue for the treatment of prostate cancer.  

PubMed

Goserelin acetate (Gos) is a luteinizing hormone-releasing hormone agonist, used in treatment of prostate cancer in which desired concentration of Gos in blood is maintained for longer duration. The aim of this study is to improve the efficacy of Gos targeted at the site of action and eliminate the need for frequent administration. Gos-encapsulated nanoparticles were fabricated by double emulsification process. The physicochemical traits of the nanoparticles including morphology, particle size, zeta-potential, entrapment efficiency, and in-vitro release profile were studied. The in-vitro cytotoxicity of the blank nanoparticles and Gos-loaded nanoparticles were also evaluated on LNCaP cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Blank methoxy PEG-poly(?-caprolactone) (mPEG-PCL) nanoparticles exhibited low cytotoxicity, which increased with increase in concentration of Gos-loaded nanoparticles. Serum Gos and testosterone levels were analyzed after subcutaneous administration in Wistar rats. In-vivo study showed that a sustained serum level of Gos successfully suppressed the plasma testosterone concentration to castration level. So, it can be concluded that mPEG-PCL nanoparticles might prove to be useful for site specific and sustain protein delivery. PMID:22380019

Tomar, Priti; Jain, Neeti; Dixit, Vinod Kumar

2012-03-02

118

Herpes simplex virus vector-mediated gene delivery for the treatment of lower urinary tract pain  

PubMed Central

Interstitial cystitis (IC)/painful bladder syndrome (PBS) is a painful debilitating chronic visceral pain disorder of unknown etiology that affects an estimated 1 million people in the, United States alone. It is characterized by inflammation of the bladder that results in chronic pelvic pain associated with bladder symptoms of urinary frequency and urgency. Regardless of the etiology, IC/PBS involves either increased and/or abnormal activity in afferent nociceptive sensory neurons. Pain-related symptoms in patients with IC/PBS are often very difficult to treat. Both medical and surgical therapies have had limited clinical utility in this debilitating disease and numerous drug treatments, such as heparin, dimethylsulfoxide and amitriptyline, have proven to be palliative at best, and in some IC/PBS patients provide no relief whatsoever. Although opiate narcotics have been employed to help alleviate IC/PBS pain, this strategy is fraught with problems as systemic narcotic administration causes multiple unwanted side effects including mental status change and constipation. Moreover, chronic systemic narcotic use leads to dependency and need for dose escalation due to tolerance: therefore, new therapies are desperately needed to treat refractory IC/PBS. This has led our group to develop a gene therapy strategy that could potentially alleviate chronic pelvic pain using the herpes simplex virus-directed delivery of analgesic proteins to the bladder.

Goins, WF; Goss, JR; Chancellor, MB; de Groat, WC; Glorioso, JC; Yoshimura, N

2009-01-01

119

A biodegradable drug delivery system for the treatment of postoperative inflammation.  

PubMed

Cataract surgery is often performed in patients suffering from associated pathologies. Our goal is to develop a biodegradable drug delivery system (DDS) combined with the artificial intraocular lens (IOL). DDS were manufactured using poly(D,L-lactide-co-glycolide), or PLGA, and were loaded with triamcinolone acetonide (TA). The loading capacity was approximately 1050 microg of TA per DDS. The higher the molecular weight of PLGA (34,000, 48,000 and 80,000Da), the slower was the release of TA in vitro. Cataract surgery was performed on the right eye of rabbits. IOL was inserted with (i) no DDS, (ii) unloaded DDS PLGA48000, (iii) one loaded DDS PLGA48000, (iv) two loaded DDS. The number of inflammatory cells and the protein concentration were measured in the aqueous humor (AH). Unloaded DDS showed good ocular biocompatibility. One DDS PLGA48000 loaded with TA significantly reduced postoperative ocular inflammation. Two loaded DDS PLGA48000 was even more effective in inhibiting such inflammation. On long-term observation (days 63 and 84), reduction of inflammation could be obtained by insertion of one DDS PLGA48000 and a second DDS PLGA80000. Therefore, our "all in one" system is very promising since it could replace oral treatment and reduce the number of intraocular injections. PMID:18093765

Eperon, S; Bossy-Nobs, L; Petropoulos, I K; Gurny, R; Guex-Crosier, Y

2007-11-17

120

Validation of Pinnacle treatment planning system for use with Novalis delivery unit.  

PubMed

For an institution that already owns the licenses, it is economically advantageous and technically feasible to use Pinnacle TPS (Philips Radiation Oncology Systems, Fitchburg, WI) with the BrainLab Novalis delivery system (BrainLAB A.G., Heimstetten, Germany). This takes advantage of the improved accuracy of the convolution algorithm in the presence of heterogeneities compared with the pencil beam calculation, which is particularly significant for lung SBRT treatments. The reference patient positioning DRRs still have to be generated by the BrainLab software from the CT images and isocenter coordinates transferred from Pinnacle. We validated this process with the end-to-end hidden target test, which showed an isocenter positioning error within one standard deviation from the previously established mean value. The Novalis treatment table attenuation is substantial (up to 6.2% for a beam directed straight up and up to 8.4% for oblique incidence) and has to be accounted for in calculations. A simple single-contour treatment table model was developed, resulting in mean differences between the measured and calculated attenuation factors of 0.0%-0.2%, depending on the field size. The maximum difference for a single incidence angle is 1.1%. The BrainLab micro-MLC (mMLC) leaf tip, although not geometrically round, can be represented in Pinnacle by an arch with satisfactory dosimetric accuracy. Subsequently, step-and-shoot (direct machine parameter optimization) IMRT dosimetric agreement is excellent. VMAT (called "SmartArc" in Pinnacle) treatments with constant gantry speed and dose rate are feasible without any modifications to the accelerator. Due to the 3 mm-wide mMLC leaves, the use of a 2 mm calculation grid is recommended. When dual arcs are used for the more complex cases, the overall dosimetric agreement for the SmartArc plans compares favorably with the previously reported results for other implementations of VMAT: gamma(3%,3mm) for absolute dose obtained with the biplanar diode array passing rates above 97% with the mean of 98.6%. However, a larger than expected dose error with the single-arc plans, confined predominantly to the isocenter region, requires further investigation. PMID:20717094

Faygelman, Vladimir; Hunt, Dylan; Walker, Luke; Mueller, Richard; Demarco, Mary Lou; Dilling, Thomas; Stevens, Craig; Zhang, Geoffrey

2010-06-15

121

Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.  

PubMed

Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC. PMID:22681390

Krishnaiah, Yellela S R; Khan, Mansoor A

2012-06-08

122

Treatment planning system and dose delivery accuracy in extracranial stereotactic radiotherapy using Elekta body frame  

NASA Astrophysics Data System (ADS)

The purpose of this study was to measure the photon beam transmission through the Elekta Stereotactic Body Frame (ESBF) and treatment couch, to determine the dose calculations accuracy of the MasterPlan Treatment Planning System (TPS) using Pencil Beam (PBA) and Collapsed Cone (CCA) algorithms during the use of Elekta Stereotactic Body Frame (ESBF), and to demonstrate a simple calculation method to put this transmission into account during the treatment planning dose calculations. The dose was measured at the center of an in-house custom-built inhomogeneous PMMA thorax phantom with and without ‘the frame + treatment couch’. The phantom was CT-imaged inside the ESBF and planned with multiple 3D-CRT fields using PBA and CCA for photon beams of energies 6 MV and 10 MV. There were two treatment plans for dose calculations. In the first plan, the ‘frame + couch’ were included in the body contour and, therefore, included in the TPS dose calculations. In the second plan, the ‘frame + couch’ were not included in the body contour and, therefore, not included in the calculations. Transmission of the ‘frame + couch’ was determined by the ratio of the dose measurements with the ‘frame + couch’ to the measurements without them. To validate the accuracy of the calculation model, plans with and without the ‘frame + couch’ surrounding the phantoms were compared with their corresponding measurements. The transmission of the ‘frame + couch’ varies from 90.23-97.54% depending on the energy, field size, the angle of the beams and whether the beams also intercept them. The validation accuracy of the Pencil Beam (PBA) and Collapsed Cone (CCA) algorithms were within 5.33% and 4.04% respectively for the individual measurements for all gantry angles under this study. The results showed that both PBA and CCA algorithms can calculate the dose to the target within 4.25% and 1.95% of the average measured value. The attenuation caused by the ESBF and couch must be accounted into the planning process. For MasterPlan, the ‘frame + couch’ should be contoured and included in all calculations. This can be done easily and accurately.

Dawod, Tamer; Bremer, Michael; Karstens, Johann H.; Werner, Martin

2010-01-01

123

Design, Fabrication and Analysis of Silicon Hollow Microneedles for Transdermal Drug Delivery System for Treatment of Hemodynamic Dysfunctions  

Microsoft Academic Search

In this paper, we present design, fabrication and coupled multifield analysis of hollow out-of-plane silicon microneedles\\u000a with piezoelectrically actuated microfluidic device for transdermal drug delivery (TDD) system for treatment of cardiovascular\\u000a or hemodynamic disorders such as hypertension. The mask layout design and fabrication process of silicon microneedles and\\u000a reservoir involving deep reactive ion etching (DRIE) is first presented. This is

M. W. Ashraf; S. Tayyaba; A. Nisar; N. Afzulpurkar; D. W. Bodhale; T. Lomas; A. Poyai; A. Tuantranont

2010-01-01

124

Ophthalmic delivery of sparfloxacin from in situ gel formulation for treatment of experimentally induced bacterial keratitis.  

PubMed

The objective of the present work was (1) to develop an in situ gelling ophthalmic delivery system by combining pluronic F127 and pluronic F68, with sparfloxacin; and (2) to examine the influence of incorporating a mucoadhesive polysaccharide such as sodium hyaluronate on the healing property due to bacterial keratitis. The formulations (F1-F6) were sterilized by gamma irradiated using Co(60) . Ultraviolet (UV) and infrared (IR) spectra studies were performed on sterilized and non-sterilized formulae. The formulations were evaluated for rheological characteristics, in vitro release behavior, and efficacy against induced bacterial conjunctivitis in rats' eyes. Moreover, histopathological evaluations were also done. All the samples passed sterility tests, and no change in physical appearance of the formulae due to gamma radiation was observed. The IR spectra of the formulae before and after sterilization showed similar peaks which confirmed that no ingredient was affected by gamma radiation. The formulations showed a flow index of 0.116-0.493 indicating pseudoplastic flow behavior. The release behavior of all formulae was non-Fickian anomalous release. The different formulae used to overcome the pathological alterations, produced by bacteria infections varied among each other depending on the duration of treatment; however, the effectiveness of formulation was arranged as F5, F4 and F3, respectively. The developed formulations were therapeutically efficacious, and provided sustained release of the drug over a 24-hour period. A better improvement in artificially induced bacterial conjunctivitis in rats' cornea was observed with the developed formulae; thus it can be considered as a viable alternative to conventional eye drops. PMID:21322120

Nesseem, Demiana I

2010-10-28

125

Efficacy of intracerebral delivery of cisplatin in combination with photon irradiation for treatment of brain tumors  

PubMed Central

We have evaluated the efficacy of intracerebral (i.c.) convection-enhanced delivery (CED) of cisplatin in combination with photon irradiation for the treatment of F98 glioma-bearing rats. One thousand glioma cells were stereotactically implanted into the brains of Fischer rats and 13 days later cisplatin (6?g/20?L) was administered i.c. by CED at a flow rate of 0.5?L/min. On the following day the animals were irradiated with a single 15 Gy dose of X-rays, administered by a linear accelerator (LINAC) or 78.8 keV synchrotron X-rays at the European Synchrotron Radiation Facility (ESRF). Untreated controls had a mean survival time (MST) ± standard error of 24 ± 1 d. compared to > 59 ± 13 d. for rats that received cisplatin alone with 13% of the latter surviving >200 d. Rats that received cisplatin in combination with either 6 MV (LINAC) or 78.8 keV (synchrotron) X-rays had almost identical MSTs of > 75±18 d. and > 74±19 d., respectively with 17% and 18% long term survivors. Microscopic examination of the brains of long term surviving rats revealed an absence of viable tumor cells and cystic areas at the presumptive site of the tumor. Our data demonstrate that i.c. CED of cisplatin in combination with external X-irradiation significantly enhanced the survival of F98 glioma-bearing rats. This was independent of the X-ray beam energy and probably was not due to the production of Auger electrons as we previously had postulated. Our data provide strong support for the approach of concomitantly administering platinum based chemotherapy in combination with radiotherapy for the treatment of brain tumors. Since a conventional LINAC can be used as the radiation source, this should significantly broaden the clinical applicability of this approach compared to synchrotron radiotherapy, which could only be carried out at a very small number of specialized facilities.

Rousseau, Julia; Barth, Rolf F.; Fernandez, Manuel; Adam, Jean-Francois; Balosso, Jacques; Esteve, Francois; Elleaume, Helene

2010-01-01

126

Treatment Planning and Delivery of External Beam Radiotherapy for Pediatric Sarcoma: The St. Jude Children's Research Hospital Experience  

SciTech Connect

Purpose: To describe and review the radiotherapy (RT) treatment planning and delivery techniques used for pediatric sarcoma patients at St. Jude Children's Research Hospital. The treatment characteristics serve as a baseline for future comparison with developing treatment modalities. Patients and Methods: Since January 2003, we have prospectively treated pediatric and young-adult patients with soft-tissue and bone sarcomas on an institutional Phase II protocol evaluating local control and RT-related treatment effects from external-beam RT (conformal or intensity-modulated RT; 83.4%), low-dose-rate brachytherapy (8.3%), or both (8.3%). Here we describe the treatment dosimetry and delivery parameters of the initial 72 patients (median, 11.6 years; range, 1.4-21.6 years). Results: Cumulative doses from all RT modalities ranged from 41.4 to 70.2 Gy (median, 50.4 Gy). Median D{sub 95} and V{sub 95} of the planning target volume of external-beam RT plans were, respectively, 93.4% of the prescribed dose and 94.6% of the target volume for the primary phase and 97.8% and 99.2% for the cone-down/boost phase. The dose-volume histogram statistics for 27 critical organs varied greatly. The spinal cord in 13 of 36 patients received dose >45 Gy (up to 52 Gy in 1 cc) because of tumor proximity. Conclusions: Planning and delivery of complex multifield external beam RT is feasible in pediatric patients with sarcomas. Improvements on conformity and dose gradients are still desired in many cases with sensitive adjacent critical structures. Long-term follow-up will determine the risk of local failure and the benefit of normal tissue avoidance for this population.

Hua Chiaho [Division of Radiation Oncology, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN (United States)], E-mail: Chia-Ho.Hua@stjude.org; Gray, Jonathan M.; Merchant, Thomas E.; Kun, Larry E.; Krasin, Matthew J. [Division of Radiation Oncology, Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN (United States)

2008-04-01

127

Liposomes as drug delivery system in the treatment of infectious diseases potential applications and clinical experience  

Microsoft Academic Search

Summary Liposomes are microscopic, closed lipid vesicles able to entrap hydrophilic as well as lipophilic compounds. They constitute a versatile drug delivery system. When injected by the intravenous route, liposomes are taken up by macrophages in the liver and in the spleen. Investigation of several animal models of infections has shown that liposome-entrapped anti-infectious drugs are active against infections due

A. Coune

1988-01-01

128

Seed treatment technology: An attractive delivery system for controlling root parasitic weed Striga with mycoherbicide  

Microsoft Academic Search

Coating sorghum seeds with Fusarium oxysporum (Foxy 2) for control of the root parasitic weed Striga, appears to be an attractive option for minimizing the inoculum amount, establishing the biocontrol agent in the potential infection zone of the host plants, and offering a simple, easy and economical delivery system. Our investigations resulted in the selection of appropriate seed coating materials

Abuelgasim Elzein; Juergen Kroschel; Vibeke Leth

2006-01-01

129

Functional Analysis and Treatment of Rumination Using Fixed-Time Delivery of a Flavor Spray  

ERIC Educational Resources Information Center

|A functional analysis suggested that rumination exhibited by an adult with autism was maintained by automatic reinforcement. Next, a preference assessment with three flavor sprays (i.e., flavored sprays used by dieters) showed that apple pie spray was most preferred. Finally, the effects of fixed-time delivery of the apple pie spray on levels of…

Wilder, David A.; Register, Martisa; Register, Stanley; Bajagic, Vedrana; Neidert, Pamela L.

2009-01-01

130

Closed-loop insulin delivery for treatment of type 1 diabetes  

PubMed Central

Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas) is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed.

2011-01-01

131

Investigating the Temporal Effects of Respiratory-Gated and Intensity-Modulated Radiotherapy Treatment Delivery on In Vitro Survival: An Experimental and Theoretical Study  

SciTech Connect

Purpose: To experimentally and theoretically investigate the temporal effects of respiratory-gated and intensity-modulated radiotherapy (IMRT) treatment delivery on in vitro survival. Methods and Materials: Experiments were designed to isolate the effects of periodic irradiation (gating), partial tumor irradiation (IMRT), and extended treatment time (gating and IMRT). V79 Chinese hamster lung fibroblast cells were irradiated to 2 Gy with four delivery methods and a clonogenic assay performed. Theoretical incomplete repair model calculations were performed using the incomplete repair model. Results: Treatment times ranged from 1.67 min (conformal radiotherapy, CRT) to 15 min (gated IMRT). Survival fraction calculations ranged from 68.2% for CRT to 68.7% for gated IMRT. For the same treatment time (5 min), gated delivery alone and IMRT delivery alone both had a calculated survival fraction of 68.3%. The experimental values ranged from 65.7% {+-} 1.0% to 67.3% {+-} 1.3%, indicating no significant difference between the experimental observations and theoretical calculations. Conclusion: The theoretical results predicted that of the three temporal effects of radiation delivery caused by gating and IMRT, extended treatment time was the dominant effect. Care should be taken clinically to ensure that the use of gated IMRT does not significantly increase treatment times, by evaluating appropriate respiratory gating duty cycles and IMRT delivery complexity.

Keall, Paul J. [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)], E-mail: Paul.Keall@stanford.edu; Chang, Michael [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Benedict, Stanley [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Thames, Howard [Department of Biomathematics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Vedam, S. Sastry [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Lin, Peck-Sun [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

2008-08-01

132

Probenecid Treatment Enhances Retinal and Brain Delivery of N-4-Benzoylaminophenylsulfonylglycine, An Anionic Aldose Reductase Inhibitor  

PubMed Central

Anion efflux transporters are expected to minimize target tissue delivery of N-[4-(benzoylaminophenyl)sulfonyl]glycine (BAPSG), a novel carboxylic acid aldose reductase inhibitor, which exists as a monocarboxylate anion at physiological conditions. Therefore, the objective of this study was to determine whether BAPSG delivery to various eye tissues including the retina and the brain can be enhanced by probenecid, a competitive inhibitor of anion transporters. To determine the influence of probenecid on eye and brain distribution of BAPSG, probenecid was administered intraperitoneally (120 mg/kg body weight; i.p.) 20 minutes prior to BAPSG (50 mg/kg; i.p.) administration. Drug disposition in various eye tissues including the retina and the brain was determined at 15 min, 1, 2 and 4 hr after BAPSG dose in male Sprauge-Dawley rats. To determine whether probenecid alters plasma clearance of BAPSG, influence of probenecid (120 mg/kg; i.p.) on the plasma pharmacokinetics of intravenously administered BAPSG (15 mg/kg) was studied as well. Finally, the effect of probenecid co-administration on the ocular tissue distribution of BAPSG was assessed in rabbits following topical (eye drop) administration. Following pretreatment with probenecid in the rat study, retinal delivery at 1 hr was increased by about 11 fold (2580 vs 244 ng/gm; p<0.05). Further, following probenecid pretreatment, significant BAPSG levels were detectable in the brain (45 ± 20 ng/gm) at 1 hr, unlike controls where the drug was not detectable. Plasma concentrations, plasma elimination half-life, and total body clearance of intravenously administered BAPSG were not altered by i.p. probenecid pretreatment. In the topical dosing study, a significant decline in BAPSG delivery was observed in the iris-ciliary body but no significant changes were observed in other tissues of the anterior segment of the eye including tears. Thus, inhibition of anion transporters is a useful approach to elevate retinal and brain delivery of BAPSG.

Sunkara, Gangadhar; Ayalasomayajula, Surya P.; DeRuiter, Jack; Kompella, Uday B.

2009-01-01

133

Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.  

PubMed

Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered. PMID:20199661

Bhaskar, Sonu; Tian, Furong; Stoeger, Tobias; Kreyling, Wolfgang; de la Fuente, Jesús M; Grazú, Valeria; Borm, Paul; Estrada, Giovani; Ntziachristos, Vasilis; Razansky, Daniel

2010-03-03

134

The neuroscientist's melting pot: immunology, cell transplantation and other delivery systems, and enlightenment of disease etiology and treatment.  

PubMed

A snapshot of the current state of play with respect to a number of neurological disease causes and their potential treatments from a cell transplantation perspective, was provided at the 14th annual meeting of American Society for Neural Therapy and Repair (ASNTR). Parkinson's disease and related studies were heavily featured, with Alzheimer's disease, aging and spinal cord injury also proving to be well represented. A number of studies looked at different delivery systems including stem cells or adeno-associated virus vectors, both as proof-of-principles and also their potential as treatments, delivering neurotrophic factors. 'Simple' ways to help battle these disorders, such as dietary modification or supplementation were also revealed. Transplantation was explored both in vivo and in cell culture, where ways to improve cell survival or cause differentiation were investigated. A few reports also shed light on the likelihood of an immune response following transplantation, an important consideration for any potential treatment. PMID:18522907

Eve, David J; Sanberg, Paul R

135

Multifunctional Tumor-Targeted Polymer-Peptide-Drug Delivery System for Treatment of Primary and Metastatic Cancers  

Microsoft Academic Search

Purpose  In order to improve drug delivery to drug-resistant ovarian tumors, we constructed a multifunctional polymer-peptide-drug\\u000a conjugate (PPDC) system for effective treatment of primary and metastatic ovarian cancers.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The PPDC consists of the poly(Ethylene Glycol) (PEG) polymeric carrier conjugated via citric acid spacers to anticancer drug\\u000a (Camptothecin, CPT), tumor targeting moiety (LRHR, a synthetic analog of luteinizing hormone-releasing hormone) and a

Pooja Chandna; Jayant J. Khandare; Elizabeth Ber; Lorna Rodriguez-Rodriguez; Tamara Minko

2010-01-01

136

Investigation of Pitch and Jaw Width to Decrease Delivery Time of Helical Tomotherapy Treatments for Head and Neck Cancer  

SciTech Connect

Helical tomotherapy plans using a combination of pitch and jaw width settings were developed for 3 patients previously treated for head and neck cancer. Three jaw widths (5, 2.5, and 1 cm) and 4 pitches (0.86, 0.43, 0.287, and 0.215) were used with a (maximum) modulation factor setting of 4. Twelve plans were generated for each patient using an identical optimization procedure (e.g., number of iterations, objective weights, and penalties, etc.), based on recommendations from TomoTherapy (Madison, WI). The plans were compared using isodose plots, dose volume histograms, dose homogeneity indexes, conformity indexes, radiobiological models, and treatment times. Smaller pitches and jaw widths showed better target dose homogeneity and sparing of normal tissue, as expected. However, the treatment time increased inversely proportional to the jaw width, resulting in delivery times of 24 {+-} 1.9 min for the 1-cm jaw width. Although treatment plans produced with the 2.5-cm jaw were dosimetrically superior to plans produced with the 5-cm jaw, subsequent calculations of tumor control probabilities and normal tissue complication probabilities suggest that these differences may not be radiobiologically meaningful. Because treatment plans produced with the 5-cm jaw can be delivered in approximately half the time of plans produced with the 2.5-cm jaw (5.1 {+-} 0.6 min vs. 9.5 {+-} 1.1 min), use of the 5-cm jaw in routine treatment planning may be a viable approach to decreasing treatment delivery times from helical tomotherapy units.

Moldovan, Monica [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Fontenot, Jonas D., E-mail: jfontenot@marybird.com [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Gibbons, John P. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States); Lee, Tae Kyu [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Rosen, Isaac I. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States); Fields, Robert S. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Hogstrom, Kenneth R. [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA (United States)

2011-01-01

137

Localized striatal delivery of GDNF as a treatment for Parkinson disease  

Microsoft Academic Search

Te n years ago, a glial cell line-derived neurotrophic factor (GDNF) that has prominent actions on nigral dopaminergic neurons, both in vitro and in animal models of Parkinson disease (PD), was discov- ered. A recently published open-label clinical trial now reports that long-term intracerebral delivery of GDNF may also markedly improve symptoms in patients with PD. Here we review the

Biljana Georgievska; Anders Björklund; Deniz Kirik

2004-01-01

138

Fentanyl pectin nasal spray: a novel intranasal delivery method for the treatment of breakthrough cancer pain.  

PubMed

Fentanyl pectin nasal spray is a novel intranasal formulation for the management of breakthrough cancer pain in patients taking and tolerant to opioids for persistent cancer pain. The pectin-based delivery modulates the product's transmucosal absorption. Nasal delivery allows fentanyl pectin nasal spray to achieve a greater maximum plasma concentration than oral transmucosal fentanyl products and at a much faster rate. Compared with intranasal fentanyl compounded with aqueous solutions, the pectin-based system decreases the maximum plasma concentration and prolongs exposure to more closely match the time course of a typical breakthrough cancer pain episode. Throughout all phases of clinical studies, it was shown to be safe and effective in doses between 100 and 800 µg per breakthrough pain episode. Fentanyl pectin nasal spray is the only proprietary intranasal fentanyl formulation in the USA and one of two in Europe. Owing to the medication's delivery system, the pharmacokinetics and subsequent dosing are unique to this product and should not be interchanged with any other proprietary or compounded fentanyl product. PMID:23272789

Bulloch, Marilyn N; Hutchison, Amber M

2013-01-01

139

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy?  

PubMed

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1-100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law-healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines. PMID:20149882

Kateb, Babak; Chiu, Katherine; Black, Keith L; Yamamoto, Vicky; Khalsa, Bhavraj; Ljubimova, Julia Y; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio; Modo, Mike; Moore, David F; Farahani, Keyvan; Okun, Michael S; Prakash, Neal; Neman, Josh; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D

2010-02-10

140

Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: What should be the policy?  

PubMed Central

Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1–100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law–healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.

Kateb, Babak; Chiu, Katherine; Black, Keith L.; Yamamoto, Vicky; Khalsa, Bhavraj; Ljubimova, Julia Y.; Ding, Hui; Patil, Rameshwar; Portilla-Arias, Jose Antonio; Modo, Mike; Moore, David F.; Farahani, Keyvan; Okun, Michael S.; Prakash, Neal; Neman, Josh; Ahdoot, Daniel; Grundfest, Warren; Nikzad, Shouleh; Heiss, John D.

2012-01-01

141

Focused ultrasound induced blood-brain barrier disruption to enhance chemotherapeutic drugs (BCNU) delivery for glioblastoma treatment  

NASA Astrophysics Data System (ADS)

Focused ultrasound has been recently found to capable of temporally and reversibly disrupt local blood-brain barrier (BBB) and opens new frontier in delivering varies type of drugs into brain for central nerve system (CNS) disorder treatment. In this study, we aim to investigate the feasibility of delivering 1, 3-bits (2-chloroethyl) -1-nitrosourea (BCNU) to treat glioblastoma in animal models and evaluate whether this approach would gain treatment efficacy. Under the presence of microbubbles administration, a 400-kHz focused ultrasound was employed to deliver burst-tone ultrasonic energy stimulation to disrupt BBB in animal brains transcranially, and in-vivo monitored by magnetic-resonance imaging (MRI). C6-glioma cells were cultured and implanted into Sprague-Dawley rats as the brain-tumor model. BCNU deposited in brain was quantified by using high-performance liquid chromatography (HPLC), and brain tissues were examined histologically. MRI was employed to longitudinal evaluate the brain tumor treatment including the analysis of tumor progression and animal survival. We confirmed that the focused ultrasound, under the secure ultrasonic energy level, can significantly enhance the BCNU penetration through BBB over 300% than control without cause hemorrhage. Apparent improvement of treatment efficacy achieved by combining focused ultrasound with BCNU delivery, including significant suppression of tumor growth and a prolonged animal survival. This study highly support that this treatment strategy could be clinically-relevant and may help to provide another potential strategy in increasing local chemotherapeutic drugs for brain-tumor treatment.

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Huang, Chiung-Yin; Wang, Jiun-Jie; Wei, Kuo-Chen

2010-03-01

142

Design and evaluation of cyclodextrin-based delivery systems to incorporate poorly soluble curcumin analogs for the treatment of melanoma.  

PubMed

Various analogs of curcumin show high in vitro cytotoxic activity and are potential candidates for treating a deadly skin disease, melanoma. Due to the low solubility of the drugs, a new delivery agent, namely a cationic gemini surfactant-conjugated ?-cyclodextrin, was designed to incorporate novel drug candidates of the 1,5-diaryl-3-oxo-1,4-pentadienyl family. Based on physicochemical parameters, such as particle size and zeta potential, a schematic model for the potential interaction of the drug with the delivery agent was developed. The drug formulations were highly efficient in inhibiting the growth of melanoma cells, with IC(50) values significantly lower than melphalan, the drug currently used for the treatment of in-transit melanoma. CDgemini formulations showed excellent cellular selectivity, triggering apoptosis in the A375 cell line while showing no cytotoxicity to healthy human epidermal keratinocytes. The goal is to develop this novel nanoparticle approach into a non-invasive therapy for in-transit melanoma metastasis that lacks adequate treatment to date. PMID:22531300

Michel, Deborah; Chitanda, Jackson M; Balogh, Réka; Yang, Peng; Singh, Jagbir; Das, Umashankar; El-Aneed, Anas; Dimmock, Jonathan; Verrall, Ronald; Badea, Ildiko

2012-04-17

143

A hydrogel composite system for sustained epi-cortical delivery of Cyclosporin A to the brain for treatment of stroke.  

PubMed

Stimulation of endogenous neural stem/progenitor cells (NSPCs) with therapeutic factors holds potential for the treatment of stroke. Cyclosporin A (CsA) is a particularly promising candidate molecule because it has been shown to act as a survival factor for these cells over a period of weeks both in vitro and in vivo; however, systemically-delivered CsA compromises the entire immune system, necessitating sustained localized delivery. Herein we describe a local delivery strategy for CsA using an epi-cortical hydrogel of hyaluronan-methylcellulose (HAMC) as the drug reservoir. Three methods of incorporating the drug into the hydrogel (solubilized, particulate, and poly(lactic-co-glycolic) acid (PLGA) microsphere-encapsulated) resulted in tunable release, spanning a period of hours to weeks. Importantly, PLGA-encapsulated CsA released from the hydrogel had equivalent bioactivity to fresh drug as measured by the neurosphere assay. Moreover, when CsA was released from the PLGA/HAMC composite that was injected on the cortex of adult mice, CsA was detected in the NSPC niche at a constant concentration for at least 24days post-implant. Thus this hydrogel composite system may be promising for the treatment of stroke. PMID:23306024

Caicco, Matthew J; Cooke, Michael J; Wang, Yuanfei; Tuladhar, Anup; Morshead, Cindi M; Shoichet, Molly S

2013-01-08

144

Unit Costs for Delivery of Antiretroviral Treatment and Prevention of Mother-to-Child Transmission of HIV: A Systematic Review for Low and Middle-Income Countries  

Microsoft Academic Search

As antiretroviral treatment (ART) for HIV\\/AIDS is scaled up globally, information on per-person costs is critical to improve efficiency in service delivery and to maximize coverage and health impact. The objective of this study was to review studies on unit costs for delivery of adult and paediatric ART per patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair

Omar Galrraga; Veronika J. Wirtz; Alejandro Figueroa-Lara; Yared Santa-Ana-Tellez; Ibrahima Coulibaly; Kirsi Viisainen; Antonieta Medina-Lara; Eline L. Korenromp

2011-01-01

145

Reversibly crosslinked nanocarriers for on-demand drug delivery in cancer treatment  

PubMed Central

Polymer micelles have proven to be one of the most versatile nanocarriers for anticancer drug delivery. However, the in vitro and in vivo stability of micelles remains a challenge due to the dynamic nature of these self-assembled systems, which leads to premature drug release and nonspecific biodistribution in vivo. Recently, reversibly crosslinked micelles have been developed to provide solutions to stabilize nanocarriers in blood circulation. Increased stability allows nanoparticles to accumulate at tumor sites efficiently via passive and/or active tumor targeting, while cleavage of the micelle crosslinkages, through internal or external stimuli, facilitates on-demand drug release. In this review, various crosslinking chemistries as well as the choices for reversible linkages in these nanocarriers will be introduced. Then, the development of reversibly crosslinked micelles for on-demand drug release in response to single or dual stimuli in the tumor microenvironment is discussed, for example, acidic pH, reducing microenvironment, enzymatic microenvironment, photoirradiation and the administration of competitive reagents postmicelle delivery.

Shao, Yu; Huang, Wenzhe; Shi, Changying; Atkinson, Sean T; Luo, Juntao

2013-01-01

146

Enhanced Topical Delivery of Tetrandrine by Ethosomes for Treatment of Arthritis  

PubMed Central

The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pKa = 7.06) with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund's complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin.

Fan, Chao; Li, Xinru; Zhou, Yanxia; Zhao, Yong; Ma, Shujin; Li, Wenjing; Liu, Yan; Li, Guiling

2013-01-01

147

Aerosol-Based Delivery of Fibroblast Cells for Treatment of Lung Diseases.  

PubMed

Abstract Background: Cell-based therapy has great potential to treat patients with lung diseases. The administration of cells into an injured lung is one method of repairing and replacing lost lung tissue. However, different types of delivery have been studied and compared, and none of the techniques resulted in engraftment of a high number of cells into the targeted organ. In this in vitro study, a novel method of cell delivery was introduced to investigate the possibility of delivering aerosolized skin-derived fibroblasts. Methods: Skin-derived fibroblasts were trypsinized and resuspended in growth medium. A syringe filled with cells (10(5) cells/mL) was attached to MicroSprayer(®) Aerosolizer, a device that can modify a liquid into an aerosol. The tip of the MicroSprayer Aerosolizer was channeled into a T25 flask containing growth medium. Survivability following aerosolization was observed on a daily basis. HeLa cells were used for comparison. The same aerosolization and culture methods were used to treat HeLa cells. Results: One day following aerosolization, skin-derived fibroblasts showed no sign of vacuolation due to cell stress. They attached to the surface of the flask, indicating that most of them survived aerosolization. The surviving cells were also able to proliferate rapidly, forming a confluent monolayer of cells at day 4. In contrast, HeLa cells were unable to proliferate even after 21 days of culture. Conclusions: This study provides the first evidence that cells can be aerosolized without the risk of low cell survivability and stress. The high survival rate of fibroblast cells following aerosolization illustrates the potential for delivering of such cells in future aerosol cell-based therapy to treat lung diseases. PMID:23409833

Kardia, E; Yusoff, N M; Zakaria, Z; Yahaya, B

2013-02-14

148

Helical Tomotherapy-Based STAT Stereotactic Body Radiation Therapy: Dosimetric Evaluation for a Real-Time SBRT Treatment Planning and Delivery Program  

SciTech Connect

Stereotactic body radiation therapy (SBRT) treatments have high-dose gradients and even slight patient misalignment from the simulation to treatment could lead to target underdosing or organ at risk (OAR) overdosing. Daily real-time SBRT treatment planning could minimize the risk of geographic miss. As an initial step toward determining the clinical feasibility of developing real-time SBRT treatment planning, we determined the calculation time of helical TomoTherapy-based STAT radiation therapy (RT) treatment plans for simple liver, lung, and spine SBRT treatments to assess whether the planning process was fast enough for practical clinical implementation. Representative SBRT planning target volumes for hypothetical liver, peripheral lung, and thoracic spine lesions and adjacent OARs were contoured onto a planning computed tomography scan (CT) of an anthropomorphic phantom. Treatment plans were generated using both STAT RT 'full scatter' and conventional helical TomoTherapy 'beamlet' algorithms. Optimized plans were compared with respect to conformality index (CI), heterogeneity index (HI), and maximum dose to regional OARs to determine clinical equivalence and the number of required STAT RT optimization iterations and calculation times were determined. The liver and lung dosimetry for the STAT RT and standard planning algorithms were clinically and statistically equivalent. For the liver lesions, 'full scatter' and 'beamlet' algorithms showed a CI of 1.04 and 1.04 and HI of 1.03 and 1.03, respectively. For the lung lesions, 'full scatter' and 'beamlet' algorithms showed a CI of 1.05 and 1.03 and HI of 1.05and 1.05, respectively. For spine lesions, 'full scatter' and 'beamlet' algorithms showed a CI of 1.15 and 1.14 and HI of 1.22 and 1.14, respectively. There was no difference between treatment algorithms with respect to maximum doses to the OARs. The STAT RT iteration time with current treatment planning systems is 45 sec, and the treatment planning required 3 iterations or 135 sec for STAT RT liver and lung SBRT plans and 7 iterations or 315 sec for STAT RT spine SBRT plans. Helical TomoTherapy-based STAT RT treatment planning with the 'full scatter' algorithm provides levels of dosimetric conformality, heterogeneity, and OAR avoidance for SBRT treatments that are clinically equivalent to those generated with the Helical TomoTherapy 'beamlet' algorithm. STAT RT calculation times for simple SBRT treatments are fast enough to warrant further investigation into their potential incorporation into an SBRT program with daily real-time planning. Development of methods for accurate target and OAR determination on megavoltage computed tomography scans incorporating high-resolution diagnostic image co-registration software and CT detector-based exit dose measurement for quality assurance are necessary to build a real-time SBRT planning and delivery program.

Dunlap, Neal; McIntosh, Alyson; Sheng Ke; Yang Wensha; Turner, Benton; Shoushtari, Asal [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Sheehan, Jason [Department of Neurosurgery, University of Virginia, Charlottesville, VA (United States); Jones, David R. [Department of Surgery, University of Virginia, Charlottesville, VA (United States); Lu Weigo; Ruchala, Keneth; Olivera, Gustavo; Parnell, Donald [TomoTherapy, Inc., Madison, WI (United States); Larner, James L.; Benedict, Stanley H. [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States); Read, Paul W., E-mail: pwr3u@virginia.ed [Department of Radiation Oncology, University of Virginia, Charlottesville, VA (United States)

2010-01-01

149

Non-antibiotic treatment recommendations: delivery formats and implications for parent resistance  

Microsoft Academic Search

This study draws on a database of 570 community-based acute pediatric encounters in the USA and uses conversation analysis as a methodology to identify two formats physicians use to recommend non-antibiotic treatment in acute pediatric care (using a subset of 309 cases): recommendations for particular treatment (e.g., “I’m gonna give her some cough medicine.”) and recommendations against particular treatment (e.g.,

Tanya Stivers

2005-01-01

150

On-demand drug delivery from self-assembled nanofibrous gels: a new approach for treatment of proteolytic disease.  

PubMed

Local delivery of drugs offers the potential for high local drug concentration while minimizing systemic toxicity, which is often observed with oral dosing. However, local depots are typically administered less frequently and include an initial burst followed by a continuous release. To maximize efficiency of therapy, it is critical to ensure that drug is only released when needed. One of the hallmarks of rheumatoid arthritis, for example, is its variable disease activity consisting of exacerbations of inflammation punctuated by periods of remission. This presents significant challenges for matching localized drug delivery with disease activity. An optimal system would be nontoxic and only release drugs during the period of exacerbation, self-titrating in response to the level of inflammation. We report the development of an injectable self-assembled nanofibrous hydrogel, from a generally recognized as safe material, which is capable of encapsulation and release of agents in response to specific enzymes that are significantly upregulated in a diseased state including matrix metalloproteinases (MMP-2 and MMP-9) and esterases. We show that these self-assembled nanofibrous gels can withstand shear forces that may be experienced in dynamic environments such as joints, can remain stable following injection into healthy joints of mice, and can disassemble in vitro to release encapsulated agents in response to synovial fluid from arthritic patients. This novel approach represents a next-generation therapeutic strategy for localized treatment of proteolytic diseases. PMID:21404422

Vemula, Praveen Kumar; Boilard, Eric; Syed, Abdullah; Campbell, Nathaniel R; Muluneh, Melaku; Weitz, David A; Lee, David M; Karp, Jeffrey M

2011-03-14

151

Intra-articular drug delivery systems for the treatment of rheumatic diseases: a review of the factors influencing their performance.  

PubMed

Osteoarthritis and rheumatoid arthritis are rheumatic diseases for which a curative treatment does not currently exist. Their management is directed towards pain relief achieved with different classes of drugs among which non-steroidal and steroidal anti-inflammatory substances are the most frequently used agents. Nevertheless, the oral or systemic administration of such drugs is hindered by numerous side effects, which could be overcome by their intra-articular (i-a.) administration as dosage forms capable of gradually releasing the active substance. The present review article summarises the research done in the field of drug delivery systems for i-a. injection vs. current management of osteoarthritis or rheumatoid arthritis. Aspects such as the influence of size, shape, polymer matrix or targeted drug on the i-a. retention time, phagocytosis and biological activity will be discussed. Finally, we will comment on the need for adapted delivery systems for the novel and very potent anti-inflammatory drugs, such as inhibitors of the p38 mitogen-activated protein kinase or the IL-1beta conversion enzyme, which to date cannot be properly used due to the severe side effects associated with their systemic administration. PMID:19545624

Butoescu, N; Jordan, O; Doelker, E

2009-06-21

152

Patient Satisfaction with HIV/AIDS Care and Treatment in the Decentralization of Services Delivery in Vietnam  

PubMed Central

Objective We evaluated the patient satisfaction with HIV/AIDS care and treatment and its determinants across levels of health service administration in Vietnam. Methods We interviewed 1016 patients at 7 hospitals and health centers in three epicenters, including Hanoi, Hai Phong, and Ho Chi Minh City. The Satisfaction with HIV/AIDS Treatment Interview Scale (SATIS) was developed, and 3 dimensions were constructed using factor analysis, namely “Quality and Convenience”; “Availability and Responsiveness”; and “Competence of health care workers”. Results In a band score of (0; 10), the mean scores of all domains were large; it was the highest in “Competence of health workers” (9.34±0.84), and the lowest in “Quality and Convenience” (9.03±1.04). The percentages of respondents completely satisfied with overall service quality and treatment outcomes were 42.4% and 18.8%, respectively. In multivariate analysis, factors related to higher satisfaction included female sex, older age, and living with spouses or partners. Meanwhile, lower satisfaction was found among patients who were attending provincial and district clinics; in the richest group; had higher CD4 count; and drug users. Conclusion This study highlights the importance of improving the quality of HIV/AIDS services at the provincial and district clinics. Potential strategies include capacity building for health workers, integrative service delivery, engagements of family members in treatment supports, and additional attention and comprehensive care for drug users with HIV/AIDS.

Tran, Bach Xuan; Nguyen, Nhung Phuong Thi

2012-01-01

153

Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study.  

PubMed

The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment. PMID:23527068

Wei, Kuo-Chen; Chu, Po-Chun; Wang, Hay-Yan Jack; Huang, Chiung-Yin; Chen, Pin-Yuan; Tsai, Hong-Chieh; Lu, Yu-Jen; Lee, Pei-Yun; Tseng, I-Chou; Feng, Li-Ying; Hsu, Peng-Wei; Yen, Tzu-Chen; Liu, Hao-Li

2013-03-19

154

A Controlled Study of a Lecithinized Delivery System of Curcumin (Meriva®) to Alleviate the Adverse Effects of Cancer Treatment.  

PubMed

A proprietary lecithin delivery system of curcumin (Meriva) was evaluated in a controlled study to assess its efficacy in alleviating the side effects of cancer chemo- and radiotherapy in 160 patients undergoing these treatments. In both cases, a semi-quantitative evaluation of the side effects was carried out using a visual analogue scale, assessing also the plasma free radical status in all patients. Results showed that lecithinized curcumin might alleviate the burden of side effects associated to chemo- and radiotherapy, suggesting that the anecdotal use of various preparations of curcumin as a supportive agent for cancer treatment is well worth a systematic investigation in larger scale clinical trials. The capacity of curcumin to upregulate anti-oxidative responses and downregulate inflammatory pathways could explain its beneficial effect in tempering the prolonged and systemic oxidative and inflammatory effects of cancer treatment, and the beneficial effects observed in the plasma oxidative status in all patients of the treatment group support this view. © 2013 The Authors. Phytotherapy Research published by John Wiley & Sons, Ltd. PMID:23775598

Belcaro, Gianni; Hosoi, Morio; Pellegrini, Luciano; Appendino, Giovanni; Ippolito, Edmondo; Ricci, Andrea; Ledda, Andrea; Dugall, Mark; Cesarone, Maria Rosaria; Maione, Claudia; Ciammaichella, Giovanna; Genovesi, Domenico; Togni, Stefano

2013-06-15

155

Infertility Treatment, ART and IUI Procedures and Delivery Outcomes: How Important is Selection?  

Microsoft Academic Search

Medical treatments such as Intra-Uterine Insemination (IUI) and Assisted Reproduction Technology (ART) that help otherwise infertile couples to get pregnant are highly successful and widely used these days. While highly successful, there have been concerns regarding the safety of these procedures and their effect on maternal and neonatal outcomes. Specifically, it has been observed that these treatments significantly increase the

Pooja G. Mookim; Randall P. Ellis; Ariella Kahn-Lang

2010-01-01

156

Improving drug abuse treatment delivery through adoption of harmonized electronic health record systems  

PubMed Central

A great divide currently exists between mainstream health care and specialty substance use disorders (SUD) treatment, concerning the coordination of care and sharing of medical information. Improving the coordination of SUD treatment with other disciplines of medicine will benefit SUD patients. The development and use of harmonized electronic health record systems (EHR) containing standardized person-level information will enable improved coordination of healthcare services. We attempt here to illuminate the urgent public health need to develop and implement at the national level harmonized EHR including data fields containing standardized vocabulary/terminologies relevant to SUD treatment. The many advantages and barriers to harmonized EHR implementation in SUD treatment service groups, and pathways to their successful implementation, are also discussed. As the US Federal Government incentivizes Medicare and Medicaid Service providers nationwide for “meaningful use” of health information technology (HIT) systems, relevant stakeholders may face relatively large and time-consuming processes to conform their local practices to meet the federal government’s “meaningful use” criteria unless they proactively implement data standards and elements consistent with those criteria. Incorporating consensus-based common data elements and standards relevant to SUD screening, diagnosis, and treatment into the federal government’s “meaningful use” criteria is an essential first step to develop necessary infrastructure for effective coordination of HIT systems among SUD treatment and other healthcare service providers to promote collaborative-care implementation of cost-effective, evidence-based treatments and to support program evaluations.

Ghitza, Udi E; Sparenborg, Steven; Tai, Betty

2011-01-01

157

Development of polysaccharide-based colon targeted drug delivery systems for the treatment of amoebiasis.  

PubMed

The main focus of this study is to develop colon targeted drug delivery systems for metronidazole (MTZ). Tablets were prepared using various polysaccharides or indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan, beta-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been selected and evaluated. The prepared tablets were tested in vitro for their suitability as colon-specific drug delivery systems. To further improve the colon specificity, some selected tablet formulations were enteric coated with Eudragit-L 100 to give protection in an acidic environment. Drug release studies were performed in simulated gastric fluid (SGF) for 2 hr followed by simulated intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate of drug release is dependent upon the nature and concentration of polysaccharide/polymer used in the formulations. Uncoated tablets containing xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug release during the initial 4-5 hr, whereas for tablets containing GG with the graft copolymer, it was 70%. After enteric coating, the release was drastically reduced to 18-24%. The other polysaccharides were unable to protect drug release under similar conditions. Preparations with xanthan gum as a matrix showed the time-dependent release behavior. Further, in vitro release was performed in the dissolution media with rat caecal contents. Results indicated an enhanced release when compared to formulations studied in dissolution media without rat caecal contents, because of microbial degradation or polymer solubilization. The nature of drug transport was found to be non-Fickian in case of uncoated formulations, whereas for the coated formulations, it was found to be super-Case-II. Statistical analyses of release data indicated that MTZ release is significantly affected by the nature of the polysaccharide used and enteric coating of the tablet. Differential scanning calorimetry indicated the presence of crystalline nature of drug in the formulations. PMID:17454058

Mundargi, Raghavendra C; Patil, Sangamesh A; Agnihotri, Sunil A; Aminabhavi, Tejraj M

2007-03-01

158

Delivery of Multiple siRNAs Using Lipid-coated PLGA Nanoparticles for Treatment of Prostate Cancer  

PubMed Central

Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called PRINT (Particle Replication In Nonwetting Templates). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32–46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer.

Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S.; Enlow, Elizabeth M.; Luft, J. Christopher; Tian, Shaomin; Napier, Mary E.; Pohlhaus, Patrick D.; Rolland, Jason P.; DeSimone, Joseph M.

2012-01-01

159

Description of a method: computer generated virtual model for accurate localisation of tumour margins, standardised resection, and planning of radiation treatment in head & neck cancer surgery.  

PubMed

Communication between the surgeon, the pathologist and the radiation oncologist is improved by a virtual model of the final resection combining 3D imaging with computer aided navigation. The pathologist localises any questionable margins and the oncologist plans focussed delivery of radiation to native tissue in an area of complex anatomy. PMID:23245946

Bittermann, Gido; Scheifele, Christian; Prokic, Vesna; Bhatt, Vyomesh; Henke, Michael; Grosu, Anca-Ligia; Schmelzeisen, Rainer; Metzger, Marc Christian

2012-12-12

160

Intracochlear Drug Delivery Systems  

PubMed Central

Introduction Advances in molecular biology and in the basic understanding of the mechanisms associated with sensorineural hearing loss and other diseases of the inner ear, are paving the way towards new approaches for treatments for millions of patients. However, the cochlea is a particularly challenging target for drug therapy, and new technologies will be required to provide safe and efficacious delivery of these compounds. Emerging delivery systems based on microfluidic technologies are showing promise as a means for direct intracochlear delivery. Ultimately, these systems may serve as a means for extended delivery of regenerative compounds to restore hearing in patients suffering from a host of auditory diseases. Areas covered in this review Recent progress in the development of drug delivery systems capable of direct intracochlear delivery is reviewed, including passive systems such as osmotic pumps, active microfluidic devices, and systems combined with currently available devices such as cochlear implants. The aim of this article is to provide a concise review of intracochlear drug delivery systems currently under development, and ultimately capable of being combined with emerging therapeutic compounds for the treatment of inner ear diseases. Expert Opinion Safe and efficacious treatment of auditory diseases will require the development of microscale delivery devices, capable of extended operation and direct application to the inner ear. These advances will require miniaturization and integration of multiple functions, including drug storage, delivery, power management and sensing, ultimately enabling closed-loop control and timed-sequence delivery devices for treatment of these diseases.

Borenstein, Jeffrey T.

2011-01-01

161

Reactor beam calculations to determine optimum delivery of epithermal neutrons for treatment of brain tumors.  

National Technical Information Service (NTIS)

Studies were performed to assess theoretical tumor control probability (TCP) for brain-tumor treatment with boron neutron capture therapy (BNCT) using epithermal neutron sources from reactors. The existing epithermal-neutron beams at the Brookhaven Medica...

F. J. Wheeler D. W. Nigg J. Capala

1997-01-01

162

Treatment of Breast Tumors using Pulsed HIFU for Delivery and Activation of Sonosensitizers.  

National Technical Information Service (NTIS)

High intensity focused ultrasound (HIFU) has been combined with a Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than...

B. E. O'Neill

2010-01-01

163

Treatment of Breast Tumors using Pulsed HIFU for Delivery and Activation of Sonosensitizers.  

National Technical Information Service (NTIS)

High intensity focused ultrasound (HIFU) has been combined with a Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than...

B. E. O'Neill

2009-01-01

164

Development and Optimization of Targeted Nanoscale Iron Delivery Methods for Treatment of NAPL Source Zones.  

National Technical Information Service (NTIS)

This project was designed to develop and evaluate innovative nanoscale zero valent iron (nZVI) technologies for application to the treatment of dense nonaqueous phase liquid (DNAPL) source zones. An integrated research program, that combined multi-scale l...

A. Ramsburg K. Pennell L. Abriola

2011-01-01

165

Telemedicine for Improved Delivery of Psychosocial Treatments for Post Traumatic Stress Disorder.  

National Technical Information Service (NTIS)

Posttraumatic stress disorder (PTSD) is considered a major public health problem in the U.S. because it has fairly high prevalence and because people with PTSD often have problems with their work, relationships, and health. There are effective treatments ...

N. Shah S. R. Thorp Z. Agha

2011-01-01

166

Competence in aspects of behavioral treatment and consultation: implications for service delivery and graduate training.  

PubMed Central

This study examined the extent to which competence in applying behavioral procedures (time-out from positive reinforcement) was sufficient to establish competence in teaching others to apply the same procedures. During baseline, graduate students attempted to instruct parents with a history of child abuse and neglect in the use of time-out. Students were then instructed in the use of time-out until they achieved proficiency in a role-play context. They then reattempted to instruct the parents. Finally, the students were instructed in certain consultation skills (i.e., teaching others to apply behavioral procedures) and again attempted to instruct parents in the application of time-out. Observations of students' consultation skills, parents' proficiency at administering time-out, and children's compliance to parental instructions revealed that explicit training in behavioral consulting skills was necessary to produce improvements in these behaviors. Students proficiency at administering time-out was insufficient to enable them to instruct others in its application. These results were corroborated by surveys of both students and staff. The implications for graduate training and service delivery are discussed.

McGimsey, J F; Greene, B F; Lutzker, J R

1995-01-01

167

Treatment planning and delivery of shell dose distribution for precision irradiation  

NASA Astrophysics Data System (ADS)

The motivation for shell dose irradiation is to deliver a high therapeutic dose to the surrounding supplying blood-vessels of a lesion. Our approach's main utility is in enabling laboratory experiments to test the much disputed hypothesis about tumor vascular damage. That is, at high doses, tumor control is driven by damage to the tumor vascular supply and not the damage to the tumor cells themselves. There is new evidence that bone marrow derived cells can reconstitute tumor blood vessels in mice after irradiation. Shell dosimetry is also of interest to study the effect of radiation on neurogenic stem cells that reside in small niche surface of the mouse ventricles, a generalized form of shell. The type of surface that we are considering as a shell is a sphere which is created by intersection of cylinders. The results are then extended to create the contours of different organ shapes. Specifically, we present a routine to identify the 3-D structure of a mouse brain, project it into 2-D contours and convert the contours into trajectories that can be executed by our platform. We use the Small Animal Radiation Research Platform (SARRP) to demonstrate the dose delivery procedure. The SARRP is a portable system for precision irradiation with beam sizes down to 0.5 mm and optimally planned radiation with on-board cone-beam CT guidance.

Matinfar, Mohammad; Iyer, Santosh; Ford, Eric; Wong, John; Kazanzides, Peter

2010-03-01

168

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study  

Microsoft Academic Search

BACKGROUND: Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health

Saidi Egwaga; Abdallah Mkopi; Nyagosya Range; Vera Haag-Arbenz; Amuri Baraka; Penny Grewal; Frank Cobelens; Hassan Mshinda; Fred Lwilla; Frank van Leth

2009-01-01

169

Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is influenced by treatment center, treatment schedule, and gender and is prognostic parameter for local control: Results of study CAO/ARO/AIO-94  

SciTech Connect

Purpose: The impact of the delivery of radiotherapy (RT) on treatment results in rectal cancer patients is unknown. Methods and Materials: The data from 788 patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III trial were analyzed concerning the impact of the delivery of RT (adequate RT: minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were analyzed as endpoints in multivariate analysis. Results: A significant difference was found between the centers and the delivery of RT. The overall delivery of RT was a prognostic factor for the LRR (no RT, 29.6% {+-} 7.8%; inadequate RT, 21.2% {+-} 5.6%; adequate RT, 6.8% {+-} 1.4%; p = 0.0001) and DFS (no RT, 55.1% {+-} 9.1%; inadequate RT, 57.4% {+-} 6.3%; adequate RT, 69.1% {+-} 2.3%; p = 0.02). Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate analysis (together with pathologic stage) but not for DFS (independent parameters, pathologic stage and age). Preoperatively, on multivariate analysis, pathologic stage, but not delivery of RT, was an independent prognostic parameter for LRR and DFS (together with adequate chemotherapy). On multivariate analysis, the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and gender were prognostic parameters for adequate RT. Conclusion: Delivery of RT should be regarded as a prognostic factor for LRR in rectal cancer and is influenced by the treatment center, treatment schedule, and patient gender.

Fietkau, Rainer [Department of Radiation Therapy, University of Rostock, Rostock (Germany)]. E-mail: rainer.fietkau@med.uni-rostock.de; Roedel, Claus [Departments of Radiation Therapy and Surgery, University of Erlangen, Erlangen (Germany); Hohenberger, Werner [Departments of Radiation Therapy and Surgery, University of Erlangen, Erlangen (Germany); Raab, Rudolf [Department of Surgery, Klinikum Oldenburg, Oldenburg (Germany); Hess, Clemens [Departments of Radiation Therapy and General Surgery, University of Goettingen, Goettingen (Germany); Liersch, Torsten [Departments of Radiation Therapy and General Surgery, University of Goettingen, Goettingen (Germany); Becker, Heinz [Departments of Radiation Therapy and General Surgery, University of Goettingen, Goettingen (Germany); Wittekind, Christian [Institute of Pathology, University of Leipzig, Leipzig (Germany); Hutter, Matthias [Department of Radiation Therapy, Krankenhaus Nordwest Frankfurt, Frankfurt (Germany); Hager, Eva [Department of Radiation Therapy, Krankenhaus Klagenfurt, Klagenfurt (Austria); Karstens, Johann [Department of Radiation Therapy, University of Hannover, Hannover (Germany); Ewald, Hermann [Department of Radiation Therapy, University of Schleswig-Holstein, Campus Kiel, Kiel (Germany); Christen, Norbert [Department of Radiation Therapy, Krankenhaus Dresden-Friedrichstadt, Dresden (Germany); Jagoditsch, Michael [Department of Surgery, Klinikum St. Veit, St. Veit (Austria); Martus, Peter [Institute of Biostatistics and Clinical Epidemiology, Charite Universitary Medicine Berlin, Berlin (Germany); Sauer, Rolf [Departments of Radiation Therapy and Surgery, University of Erlangen, Erlangen (Germany)

2007-03-15

170

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study  

PubMed Central

Background Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health system, Tanzania introduced patient centred treatment (PCT). PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice. The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken. The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes Methods Cohort analysis comparing patients treated under the PCT strategy (registered April-September 2006) with patients treated under health-facility-based DOT (registered April-September 2005). The primary outcome was the cure rate. Differences were assessed by calculating the risk ratios. Associations between characteristics of the supporters and treatment outcomes in the group of patients opting for home-based DOT were assessed through logistic regression. Results In the PCT cohort there were 1208 patients and 1417 were included in the historic cohort. There was no significant difference in cure rates between the cohorts (risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.96-1.16). In the PCT cohort, significantly more patients had successful treatment (cure or treatment completed; RR: 1.10; 95%CI: 1.01-1.15). There were no characteristics of supporters that were associated with treatment outcome. Conclusion The PCT approach showed similar cure rates and better treatment success rates compared to daily health-facility DOT. The results indicate that there are no specific prerequisites for the supporter chosen by the patient. The programmatic setting of the study lends strong support for scaling-up of TB treatment observation outside the health facility.

2009-01-01

171

Imaging revolution and radiation oncology: use of CT ultrasound, and NMR for localization, treatment planning and treatment delivery  

SciTech Connect

The explosion of new imaging technologies such as X ray computed tomography (CT), ultrasound (US), positron emission tomography (PET), and nuclear magnetic resonance imaging (NMR) has forced a major change in radiation therapy treatment planning philosophy and procedures. Modern computer technology has been wedded to these new imaging modalities, making possible sophisticated radiation therapy treatment planning using both the detailed anatomical and density information that is made available by CT and the other imaging modalities. This had forced a revolution in the way treatments are planned, with the result that actual beam configurations are typically both more complex and more carefully tailored to the desired target volume. This increase in precision and accuracy will presumably improve the results of radiation therapy.

Glatstein, E.; Lichter, A.S.; Fraass, B.A.; Kelly, B.A.; van de Geijn, J.

1985-02-01

172

Various Non-Injectable Delivery Systems for the Treatment of Diabetes Mellitus  

Microsoft Academic Search

Diabetes mellitus (diabetes) is suffered by more than 180 million people and is responsible for approximately 2.9 million deaths each year. This mortality rate is expected to increase by 50 % in the next decade. Due to the inconven- ience of the traditional treatment of diabetes by subcutaneous administration of insulin injection, various attempts are made in the production, purification,

Neha Yadav; Gordon Morris; S. E. Harding; Shirley Ang; G. G. Adams

2009-01-01

173

Treatment guidelines and techniques in delivery of postmastectomy radiotherapy in management of operable breast cancer.  

PubMed

Radiation therapy has been shown to statistically significantly reduce the risk of locoregional recurrence in high-risk patients with operable breast cancer following mastectomy and systemic therapy. Recent trials have also demonstrated a significant survival benefit following radiotherapy in high-risk patients. Therefore, it is important to identify the patients who could potentially derive that survival benefit and to not offer treatment to those patients who are not at increased risk for failure. Established risk factors that predict for increased rates of locoregional recurrence include axillary lymph node involvement and T3 (or T4) disease. While treatment-related factors, such as the extent of the axillary dissection and extent of lymph nodal positivity, also undoubtedly affect locoregional recurrence, additional studies are needed to define the magnitude of their risk. Locoregional patterns of failure have identified the chest wall and supraclavicular/infraclavicular regions to be the most common sites of locoregional failure following mastectomy, which justifies treatment to these regions. While long-term complications are uncommon following locoregional radiotherapy, careful treatment planning is critical to minimize cardiac (and pulmonary) toxicity. PMID:11773304

Pierce, L J

2001-01-01

174

A novel drug delivery system: A biodegradable gel for the treatment of inner ear diseases  

Microsoft Academic Search

Objectives: Recent experimental studies have demonstrated the efficacy of various agents including neurotrophins for the treatment of inner ear diseases. However, clinical application of these findings has rarely been realized. One possible reason for this is that the strategy for application of these agents has not been established. In this study, we examined the efficacy of the biodegradable gel for

Tsuyoshi Endo; Takayuki Nakagawa; Tomoko Kita; Tae Soo Kim; Fukuichiro Iguchi; Yasushi Naito; Yasuhiko Tabata; Juichi Ito

2004-01-01

175

Predictors of Placement Outcomes in Treatment Foster Care: Implications for Foster Parent Selection and Service Delivery  

Microsoft Academic Search

Treatment foster care (TFC) is a normalizing environment in which to treat those children whose particular needs are not addressed in traditional foster care and for whom an institutional setting is a restrictive and unnecessary alternative. However, when the foster care placements of these emotionally and behaviorally disturbed children fail, as they often do, the children are shifted from one

Richard E. Redding; Carrie Fried; Preston A. Britner

2000-01-01

176

The developmental psychopathology of perinatal depression: implications for psychosocial treatment development and delivery in pregnancy.  

PubMed

Taking a developmental psychopathology perspective, our objective was to identify ways in which psychosocial treatment of depression during pregnancy may be enhanced. We first consider the state of evidence on psychosocial interventions for antenatal depression, next define key developmental psychopathology concepts that are relevant to antenatal depression, and finally discuss implications for clinical practice and research. We found a limited, but promising, evidence base for effective psychosocial interventions for depression during pregnancy. Examining antenatal depression from a developmental psychopathology perspective revealed suggestions for improving treatment. A developmental psychopathology perspective suggests that treatment of depression during pregnancy may be improved by attention to the continuum of depression, from subclinical to severe major depressive disorder; personalized care based on individual women's pattern of risk and resilience factors and correlated risks; consideration of the potential benefits of treating the couple's relationship, the mother's qualities of parenting, and infants' and children's mental health needs; and, including a detailed understanding of the developmental pathways to antenatal depression for each patient in treatment planning. PMID:23073030

Goodman, Sherryl H; Dimidjian, Sona

2012-09-01

177

Long-Term Effects of Methylphenidate Transdermal Delivery System Treatment of ADHD on Growth  

ERIC Educational Resources Information Center

|Objective: To examine the long-term effects of the methylphenidate transdermal system (MTS) on the growth of children being treated for attention-deficit/hyperactivity disorder. Method: Height, weight, and body mass index (BMI) were measured in 127 children ages 6 to 12 at longitudinal assessments for up to 36 months of treatment with MTS. These…

Faraone, Stephen V.; Giefer, Eldred E.

2007-01-01

178

Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation  

Microsoft Academic Search

Over the last decade a new cancer treatment modality, electrochemotherapy, has emerged. By using short, intense electric pulses that surpass the capacitance of the cell membrane, permeabilization can occur (electroporation). Thus, molecules that are otherwise non-permeant can gain direct access to the cytosol of cells in the treated area.A highly toxic molecule that does not usually pass the membrane barrier

Anita Gothelf; Lluis M Mir; Julie Gehl

2003-01-01

179

Biological evaluation of a novel chitosan-PVA-based local delivery system for treatment of periodontitis.  

PubMed

In the study, we intend to design a suitable localized drug delivery system (LDDS) with chitosan and poly vinyl alcohol (PVA) for treating serve periodontitis. For that, a novel formulation based on the incorporation of chitosan-based microspheres into PVA film was prepared. As the core parts of the novel formulation, chitosan-based microspheres were prepared form chitosan and/or carboxymethyl-chitosan (CM-chitosan) by using water-in-oil emulsification method. Then basic in vitro and in vivo experiments focusing on biocompatibility and biodegradability of the two chitosan-based microspheres were carried out to evaluate the feasibility of the novel LDDS. In vitro tests, besides having no hemolysis, chitosan microsphere (Cs1-Ms), and CM-chitosan microsphere (Cs2-Ms) have adsorbed little proteins on their surfaces. Moreover, plasma proteins adsorbed on Cs2-Ms, most of which can easily desorbed, are much less than that adsorbed on Cs1-Ms. This indicates that Cs2-Ms perhaps has better biocompatibility than Cs1-Ms. In vivo tests, Cs1-Ms and Cs2-Ms were subcutaneously implanted in rat to investigate the host tissue inflammatory response. Implantations of Cs1-Ms and Cs2-Ms induced a little more severe inflammation when compared with the implantation of PVA film. However, the difference on in vivo biocompatibility between Cs1-Ms and Cs2-Ms could not be confirmed by the implantation model of our experiments. Both Cs1-Ms and Cs2-Ms had suffered bioerosion when they were subcutaneously implanted. The hard and compact matrixes of Cs1-Ms were degraded very slowly, and only some trifling degradation had been found until 4 weeks of implantation. In contrast, Cs2-Ms is soft and more hydrophilic, and can be quickly degraded in a form of diffluence by the physiological circumstance. All these results suggested that Cs2-Ms had better potentials used as core parts of the novel designed LDDS in the future developments. PMID:19107793

Wang, Ling Chong; Wu, Hao; Chen, Xi Guang; De Li, Li; Ji, Qiu Xia; Liu, Cheng Sheng; Yu, Le Jun; Ran, Chao; Zhao, Qing Sheng

2009-12-15

180

Estimation of Skin Target Site Acyclovir Concentrations Following Controlled (Trans)dermal Drug Delivery in Topical and Systemic Treatment of Cutaneous HSV1 Infections in Hairless Mice  

Microsoft Academic Search

The use of controlled transdermal delivery of acyclovir (AC V) in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice was investigated. Using an in vivoanimal model (A. Gonsho, et al. Int. J. Pharm. 65:183–194 (1990)) made it possible to quantify both, the topical and the systemic antiviral efficacy of ACV transdermal patches as a function

George Imanidis; Wei-qi Song; Paul H. Lee; Muh-Hwan Su; Earl R. Kern; William I. Higuchi

1994-01-01

181

American Academy of Periodontology Statement on Local Delivery of Sustained or Controlled Release Antimicrobials as Adjunctive Therapy in the Treatment of Periodontitis  

Microsoft Academic Search

S ustained or controlled release local delivery antimicrobial agents (LDAs) are available for use as adjuncts to scaling and root planing (SRP) in the treatment of periodontitis. These prod- ucts are placed into periodontal pockets in order to reduce subgingival bacterial flora and clinical signs of periodontitis. This therapy cannot correct ana- tomical deformities caused by the disease process. Use

2006-01-01

182

Intraosseous infusion is unreliable for adenosine delivery in the treatment of supraventricular tachycardia.  

PubMed

Supraventricular tachycardia (SVT) is a common tachyarrhythmia in the pediatric population that can necessitate immediate treatment. Adenosine has been well studied as a mainstay treatment, but the methods of adenosine administration have not been very well delineated. The intraosseous technique has presented itself as a possible method of administration. We describe 2 cases in which adenosine was administered through bone marrow infusion to convert SVT without success. The cases we describe show that intraosseous is not a reliable method of administering adenosine to stop SVT. Both patients presented with SVT refractory to vagal maneuvers and difficult intravenous placement. Intraosseous access was achieved, but administration of adenosine at increasing doses was unable to successfully convert the arrhythmia. PMID:22217885

Goodman, Ian Scott; Lu, Christina Jennifer

2012-01-01

183

Gene therapy delivery of endostatin enhances the treatment efficacy of radiation  

Microsoft Academic Search

Backgroundandpurpose: To evaluate whether sustained expression of mouse endostatin by adeno-associated virus (AAV)-mediated gene transfer can enhance the treatment efficacy of ionizing radiation.Materialsandmethods: Mouse endostatin was cloned into recombinant AAV (rAAV) under the control of CMV ?-actin promoter. Recombinant mouse endostatin expressed via AAV gene transfer was tested for biological activity in endothelial cells. The impact of elevated serum levels

Wenyin Shi; Christian Teschendorf; Nicholas Muzyczka; Dietmar W Siemann

2003-01-01

184

Long-Term Results of Radiofrequency Energy Delivery for the Treatment of GERD: Results of a Prospective 48-Month Study  

PubMed Central

Since 2000, radiofrequency (RF) energy treatment has been increasingly offered as an alternative option to invasive surgical procedures for selected patients with gastroesophageal reflux disease (GERD). Out of 69 patients treated since June 2002 to December 2007 with the Stretta procedure, 56 of them reached by the end of 2010 a 48-month followup. RF treatment significantly improved heartburn scores, GERD-specific quality of life scores, and general quality of life scores at 24 and 48 months in 52 out of 56 patients (92,8%). At each control time both mean heartburn and GERD HRQL scores decreased (P = 0.001 and P = 0.003, resp.) and both mental SF-36 and physical SF-36 ameliorated (P = 0.001 and 0.05, resp.). At 48 months, 41 out of 56 patients (72,3%) were completely off PPIs. Morbidity was minimal, with only one relevant but transient complication. According to other literature data, this study shows that RF delivery to LES is safe and durably improves symptoms and quality of life in well-selected GERD patients.

Dughera, Luca; Navino, Monica; Cassolino, Paola; De Cento, Mariella; Cacciotella, Luca; Cisaro, Fabio; Chiaverina, Michele

2011-01-01

185

Intrafraction tumor motion management techniques in imaging, treatment planning, and IMRT delivery  

NASA Astrophysics Data System (ADS)

Anatomic motion can affect the radiation treatment of disease sites in the thorax and abdomen. With four dimensional (4D) imaging modalities, respiratory motion can be defined on a patient specific basis. From 4D data sets, radiotherapy techniques can be devised to account for tissue motion. Systematic and random uncertainties must be characterized for each 4D imaging modality utilized. Some modalities, such as 4D-CT, require multiple motion trajectories in order to fully define the uncertainties associated with the imaging system. This is investigated in this work for a clinical 4D-CT scanning protocol and the methods used can be applied to any 4D imaging modality. Once all of the relevant tissues and their associated motion have been defined, with corrections to account for any associated uncertainties in the 4D data sets, treatment plans can be generated. For lung cancer, unique challenges arise when inverse planning is used, typically in the case of IMRT, because density differences between lung tissue and other tissues can result in quite different dose distributions. Because inverse planning is an optimization algorithm, the degree of optimization is dependent on the input parameters. One important input factor is the image set that is used for the dose calculation. For three image sets supplied to a commercial inverse planning algorithm (Average Image and an exhale phase image with motion envelope defined from a maximum intensity projection image, both with and without a density override to the motion envelope), dose calculated on the Average Image was found to be in best agreement with the dose calculated on the 4D-CT. Finally, when IMRT is delivered to mobile tumors, it is possible for the dose to the tumor to vary from treatment to treatment. Therefore, numerous methods have been investigated in order to reduce this variation. A computer simulation algorithm has been developed to predict the variation on a two spatial dimension plane and comparisons are made with measured data in a similar configuration. Variable tumor motion has also been considered in this respect.

Ehler, Eric Drew

186

Drug delivery through the skin barrier enhanced by treatment with tissue-tolerable plasma.  

PubMed

Most treatments in dermatology and cosmetology are based on the penetration of topically applied drugs into the skin or through the skin barrier to the target structure in the living tissue. In the case of healthy skin, scarcely 1% of the applied drugs pass the skin barrier, depending on their chemical properties. Therefore, different physical and chemical methods have been developed to stimulate the penetration process. All these methods are based on the partial destruction of the barrier. In this study, an electrical tissue-tolerable plasma (TTP) was used to increase the penetration of a topically applied model drug (fluorescent dye) through the skin barrier. Using laser scanning microscopy, the distribution of the model drug in different depths of the skin was investigated. It was found that the plasma treatment of the skin is a very efficient process to deliver topically applied substances into the living tissue. In the case of the non-plasma-treated skin, it was found that the fluorescent dye could be detected exclusively on the skin surface. If the dye was applied to the TTP-treated skin, it could be observed in high concentration also in deeper parts of the skin extending down to the stratum basale and the papillary structure. PMID:21371126

Lademann, Olaf; Richter, Heike; Meinke, Martina C; Patzelt, Alexa; Kramer, Axel; Hinz, Peter; Weltmann, Klaus-Dieter; Hartmann, Bernd; Koch, Stefan

2011-03-03

187

Iontophoretic delivery of apomorphine  

Microsoft Academic Search

Apomorphine is a mixed dopamine D1\\/D2 receptor agonist which is potentially useful in the treatment of Parkinson’s disease. The delivery of apomorphine is however complicated because it is not absorbed orally and other delivery routes with the exception of the intravenous route seem to fail. The most interesting route for controlled delivery of apomorphine is transdermal iontophoresis because this could

H. E Junginger

2002-01-01

188

Adaptive radiation therapy for compensation of errors in patient setup and treatment delivery  

SciTech Connect

In this paper, an adaptive radiation therapy algorithm is derived and evaluated using numerical simulations. Patient setup errors are considered and an off-line adaptive method to compensate for the effect of these is provided. The method consists of two parts, one for correction of patient position to account for the systematic error, and one for modulation of the fluence profiles to account for the random errors. The method is based on standard control theory for linear systems. It is investigated if this adaptive method can replace the use of a planning target volume (PTV) and therefore increase the possibilities to escalate the dose. Numerical simulations of treatments of a prostate patient indicate that this is the case. The simulations show that better organ-at-risk protection can be achieved when using the adaptation algorithm to correct for the geometrical uncertainties than when using a PTV.

Rehbinder, Henrik; Forsgren, Camilla; Loef, Johan [RaySearch Laboratories AB, Stockholm (Sweden)

2004-12-01

189

Targeted delivery of albumin bound paclitaxel in the treatment of advanced breast cancer  

PubMed Central

Taxanes are chemotherapeutic agents with a large spectrum of antitumor activity when used as monotherapy or in combination regimens. Paclitaxel and docetaxel have poor solubility and require a complex solvent system for their commercial formulation, Cremophor EL® (CrEL) and Tween 80® respectively. Both these biological surfactants have recently been implicated as contributing not only to the hypersensitivity reactions, but also to the degree of peripheral neurotoxicity and myelosuppression, and may antagonize the cytotoxicity. Nab-paclitaxel, or nanoparticle albumin-bound paclitaxel (ABI-007; Abraxane®), is a novel formulation of paclitaxel that does not employ the CrEL solvent system. Nab-paclitaxel demonstrates greater efficacy and a favorable safety profile compared with standard paclitaxel in patients with advanced disease (breast cancer, non-small cell lung cancer, melanoma, ovarian cancer). Clinical studies in breast cancer have shown that nab-paclitaxel is significantly more effective than standard paclitaxel in terms of overall objective response rate (ORR) and time to progression. Nab-paclitaxel in combination with gemcitabine, capecitabine or bevacizumab has been shown to be very active in patients with advanced breast cancer. An economic analysis showed that nab-paclitaxel would be an economically reasonable alternative to docetaxel or standard paclitaxel in metastatic breast cancer. Favorable tumor ORR and manageable toxicities have been reported for nab-paclitaxel as monotherapy or in combination treatment in advanced breast cancer.

Di Costanzo, Francesco; Gasperoni, Silvia; Rotella, Virginia; Di Costanzo, Federica

2009-01-01

190

Reactor beam calculations to determine optimum delivery of epithermal neutrons for treatment of brain tumors  

SciTech Connect

Studies were performed to assess theoretical tumor control probability (TCP) for brain-tumor treatment with boron neutron capture therapy (BNCT) using epithermal neutron sources from reactors. The existing epithermal-neutron beams at the Brookhaven Medical Research Reactor Facility (BMRR), the Petten High Flux Reactor Facility (HWR) and the Finnish Research Reactor 1 (FIR1) have been analyzed and characterized using common analytical and measurement methods allowing for this inter-comparison. Each of these three facilities is unique and each offers an advantage in some aspect of BNCT, but none of these existing facilities excel in all neutron-beam attributes as related to BNCT. A comparison is therefore also shown for a near-optimum reactor beam which does not currently exist but which would be feasible with existing technology. This hypothetical beam is designated BNCT-1 and has a spectrum similar to the FIR-1, the mono-directionality of the HFR and the intensity of the BMRR. A beam very similar to the BNCT-1 could perhaps be achieved with modification of the BMRR, HFR, or FIR, and could certainly be realized in a new facility with today`s technology.

Wheeler, F.J.; Nigg, D.W. [Idaho National Engineering & Environmental Lab., Idaho Falls, ID (United States); Capala, J. [Brookhaven National Lab., Upton, NY (United States)] [and others

1997-10-01

191

Fentanyl Buccal Tablet for the Treatment of Breakthrough Pain: Pharmacokinetics of Buccal Mucosa Delivery and Clinical Efficacy  

PubMed Central

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA®, Cephalon, Inc.) employs OraVescent® drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP.

Darwish, Mona; Hamed, Ehab; Messina, John

2010-01-01

192

Fentanyl buccal tablet for the treatment of breakthrough pain: pharmacokinetics of buccal mucosa delivery and clinical efficacy.  

PubMed

The treatment of breakthrough pain (BTP), a transitory exacerbation of pain that occurs on a background of otherwise-controlled, persistent pain, requires an opioid formulation and/or method of administration that can provide rapid and extensive systemic exposure. Fentanyl buccal tablet (FBT; FENTORA((R)), Cephalon, Inc.) employs OraVescent((R)) drug delivery technology, which enhances the rate and extent of fentanyl absorption. OraVescent technology enhances the oral dissolution and buccal absorption of fentanyl, which facilitates rapid uptake of fentanyl into the bloodstream, reducing gastrointestinal absorption and minimizing extensive first-pass metabolism. The resulting pharmacokinetic profile of FBT is characterized by greater bioavailability and a higher early systemic exposure compared with the earlier oral transmucosal fentanyl citrate formulation. In clinical studies of opioid-tolerant patients with cancer-related and noncancer-related BTP, FBT has provided consistent and clinically relevant improvements in pain intensity and pain relief relative to placebo, with a safety and tolerability profile that is generally typical of that observed with other potent opioids. The pharmacokinetic properties of FBT allow for meaningful clinical efficacy, with an onset of action that closely matches the onset of BTP. PMID:20634985

Darwish, Mona; Hamed, Ehab; Messina, John

2010-06-04

193

Are mobile phones and handheld computers being used to enhance delivery of psychiatric treatment? A systematic review.  

PubMed

The rapid diffusion of communication technology has provided opportunities to enhance the delivery of mental health care. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct a qualitative review of randomized controlled trials that reported on the efficacy of mobile phones or handheld computers used to enhance the treatment of psychiatric disorders. We identified eight randomized controlled trials. Five studies used mobile phones to target smoking cessation. Those receiving the smoking cessation intervention were significantly more likely to achieve abstinence compared with those under the control condition. Three studies used non-personal digital assistant (PDA) handheld computers targeting anxiety. Compared with those in the control condition, those who received the non-PDA handheld computer intervention had significant improvement in anxiety outcomes in only one of the three studies. The limited number of rigorous evaluations of mobile phone, PDA, or smartphone interventions for mental health problems underscores the opportunities to enhance our interventions using the available tools of contemporary technology. PMID:22048142

Ehrenreich, Benjamin; Righter, Bryan; Rocke, Di Andra; Dixon, Lisa; Himelhoch, Seth

2011-11-01

194

Biopolymeric mucoadhesive bilayer patch of pravastatin sodium for buccal delivery and treatment of patients with atherosclerosis.  

PubMed

Mucoadhesive bilayer buccal patch has been developed to improve the bioavailability and therapeutic efficacy along with providing sustained release of pravastatin sodium. Buccal patches comprising of varying composition of Carbopol 934P and HPMC K4M were designed and characterized for surface pH, swelling index, in vitro bioadhesion, mechanical properties, in vitro drug release and in vivo pharmacokinetic and pharmacodynamics performance. All formulations exhibited satisfactory technological parameters and followed non-fickian drug release mechanism. Bilayer buccal patch containing Carbopol 934P and HPMC K4M in 4:6 ratio (PBP5) was considered optimum in terms of swelling, mucoadhesion, mechanical properties and in vitro release profile. Pharmacokinetic studies in rabbits showed significantly higher (p < 0.05) Cmax (75.63 ± 6.98 ng/mL), AUC(0-8) (311.10 ± 5.89 ng/mL/h) and AUC(0-?) (909.42 ± 5.89 ng/mL/h) than pravastatin oral tablet (Cmax - 67.40 ± 9.23 ng/mL, AUC(0-8)-130.33 ± 10.25 ng/mL/h and AUC(0-?)-417.17 ± 5.89 ng/mL/h)). While, increased tmax of buccal patch indicated its sustained release property in comparison to oral tablet. Pharmacodynamic studies in rabbits showed statistically significant difference (p < 0.005) in the reduction of TG (131.10 ± 10.23 mg/dL), VLDL (26.00 ± 2.56 mg/dL) and LDL level (8.99 ± 3.01 mg/dL) as compared to oral conventional tablet. In conclusion, bioavailability from the developed buccal patch of pravastatin was 2.38 times higher than the oral dosage form, indicating its therapeutic potential in the treatment of atherosclerosis. PMID:22630116

Yedurkar, Pramod; Dhiman, Munish Kumar; Petkar, Kailash; Sawant, Krutika

2012-05-26

195

Molecular target validation, antimicrobial delivery, and potential treatment of Toxoplasma gondii infections.  

PubMed

Toxoplasma gondii persistently infects over two billion people worldwide. It can cause substantial morbidity and mortality. Existing treatments have associated toxicities and hypersensitivity and do not eliminate encysted bradyzoites that recrudesce. New, improved medicines are needed. Transductive peptides carry small molecule cargos across multiple membranes to enter intracellular tachyzoites and encysted bradyzoites. They also carry cargos into retina when applied topically to eyes, and cross blood brain barrier when administered intravenously. Phosphorodiamidate morpholino oligomers (PMO) inhibit gene expression in a sequence-specific manner. Herein, effect of transductive peptide conjugated PMO (PPMO) on tachyzoite protein expression and replication in vitro and in vivo was studied. Initially, sequence-specific PPMO successfully reduced transfected T. gondii's fluorescence and luminescence. PPMO directed against T. gondii's dihydrofolate reductase (DHFR), an enzyme necessary for folate synthesis, limited tachyzoite replication. Rescue with exogenous folate demonstrated DHFR PPMO's specificity. PPMO directed against enoyl-ACP reductase (ENR), an enzyme of type II fatty acid synthesis that is structurally distinct in T. gondii from ENR in mammalian cells was investigated. PPMO directed against plant-like Apetela 2 (AP2) domain transcription factor XI-3 (AP2XI-3), not present in human cells, was characterized. ENR and AP2XI-3 PPMO each restricted intracellular parasite replication validating these molecular targets in tachyzoites. DHFR-specific PPMO administered to infected mice diminished parasite burden. Thus, these antisense oligomers are a versatile approach to validate T. gondii molecular targets, reduce essential T. gondii proteins in vitro and in vivo, and have potential for development as curative medicines. PMID:22891343

Lai, Bo-Shiun; Witola, William H; El Bissati, Kamal; Zhou, Ying; Mui, Ernest; Fomovska, Alina; McLeod, Rima

2012-08-13

196

Molecular target validation, antimicrobial delivery, and potential treatment of Toxoplasma gondii infections  

PubMed Central

Toxoplasma gondii persistently infects over two billion people worldwide. It can cause substantial morbidity and mortality. Existing treatments have associated toxicities and hypersensitivity and do not eliminate encysted bradyzoites that recrudesce. New, improved medicines are needed. Transductive peptides carry small molecule cargos across multiple membranes to enter intracellular tachyzoites and encysted bradyzoites. They also carry cargos into retina when applied topically to eyes, and cross blood brain barrier when administered intravenously. Phosphorodiamidate morpholino oligomers (PMO) inhibit gene expression in a sequence-specific manner. Herein, effect of transductive peptide conjugated PMO (PPMO) on tachyzoite protein expression and replication in vitro and in vivo was studied. Initially, sequence-specific PPMO successfully reduced transfected T. gondii’s fluorescence and luminescence. PPMO directed against T. gondii’s dihydrofolate reductase (DHFR), an enzyme necessary for folate synthesis, limited tachyzoite replication. Rescue with exogenous folate demonstrated DHFR PPMO‘s specificity. PPMO directed against enoyl-ACP reductase (ENR), an enzyme of type II fatty acid synthesis that is structurally distinct in T. gondii from ENR in mammalian cells was investigated. PPMO directed against plant-like Apetela 2 (AP2) domain transcription factor XI-3 (AP2XI-3), not present in human cells, was characterized. ENR and AP2XI-3 PPMO each restricted intracellular parasite replication validating these molecular targets in tachyzoites. DHFR-specific PPMO administered to infected mice diminished parasite burden. Thus, these antisense oligomers are a versatile approach to validate T. gondii molecular targets, reduce essential T. gondii proteins in vitro and in vivo, and have potential for development as curative medicines.

Lai, Bo-Shiun; Witola, William H.; El Bissati, Kamal; Zhou, Ying; Mui, Ernest; Fomovska, Alina; McLeod, Rima

2012-01-01

197

Selective Delivery of a Therapeutic Gene for Treatment of Head and Neck Squamous Cell Carcinoma Using Human Neural Stem Cells  

PubMed Central

Objectives Based on studies of the extensive tropism of neural stem cells (NSCs) toward malignant brain tumor, we hypothesized that NSCs could also target head and neck squamous cell carcinoma (HNSCC) and could be used as a cellular therapeutic delivery system. Methods To apply this strategy to the treatment of HNSCC, we used a human NSC line expressing cytosine deaminase (HB1.F3-CD), an enzyme that converts 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), an anticancer agent. HB1. F3-CD in combination with 5-FC were cocultured with the HNSCC (SNU-1041) to examine the cytotoxicity on target tumor cells in vitro. For in vivo studies, an HNSCC mouse model was created by subcutaneous implantation of human HNSCC cells into athymic nude mice. HB1.F3-CD cells were injected into mice using tumoral, peritumoral, or intravenous injections, followed by systemic 5-FC administration. Results In vitro, the HB1.F3-CD cells significantly inhibited the growth of an HNSCC cell line in the presence of the 5-FC. Independent of the method of injection, the HB1.F3-CD cells migrated to the HNSCC tumor, causing a significant reduction in tumor volume. In comparison to 5-FU administration, HB1.F3-CD cell injection followed by 5-FC administration reduced systemic toxicity, but achieved the same level of therapeutic efficacy. Conclusion Transplantation of human NSCs that express the suicide enzyme cytosine deaminase combined with systemic administration of the prodrug 5-FC may be an effective regimen for the treatment of HNSCC.

Kim, Seung U; Song, Jae-Jun; Cho, Chang Gun; Park, Seok-Won

2013-01-01

198

Co-delivery of docetaxel and endostatin by a biodegradable nanoparticle for the synergistic treatment of cervical cancer.  

PubMed

Cervical cancer remains a major problem in women's health worldwide. In this research, a novel biodegradable d-?-tocopheryl polyethylene glycol 1000 succinate-b-poly(?-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was developed as a co-delivery system of docetaxel and endostatin for the synergistic treatment of cervical cancer. Docetaxel-loaded TPGS-b-(PCL-ran-PGA) NPs were prepared and further modified by polyethyleneimine for coating plasmid pShuttle2-endostatin. All NPs were characterized in size, surface charge, morphology, and in vitro release of docetaxel and pDNA. The uptake of coumarin 6-loaded TPGS-b-(PCL-ran-PGA)/PEI-pDsRED by HeLa cells was observed via fluorescent microscopy and confocal laser scanning microscopy. Endostatin expression in HeLa cells transfected by TPGS-b-(PCL-ran-PGA)/PEI-pShuttle2-endostatin NPs was detected using Western blot analysis, and the cell viability of different NP-treated HeLa cells was determined by MTT assay. The HeLa cells from the tumor model, nude mice, were treated with various NPs including docetaxel-loaded-TPGS-b-(PCL-ran-PGA)/PEI-endostatin NPs, and their survival time, tumor volume and body weight were monitored during regimen process. The tumor tissue histopathology was analyzed using hematoxylin and eosin staining, and microvessel density in tumor tissue was evaluated immunohistochemically. The results showed that the TPGS-b-(PCL-ran-PGA)/PEI NPs can efficiently and simultaneously deliver both coumarin-6 and plasmids into HeLa cells, and the expression of endostatin was verified via Western blot analysis. Compared with control groups, the TPGS-b-(PCL-ran-PGA)/PEI-pShuttle2-endostatin NPs significantly decreased the cell viability of HeLa cells (p < 0.01), inhibited the growth of tumors, and even eradicated the tumors. The underlying mechanism is attributed to synergistic anti-tumor effects by the combined use of docetaxel, endostatin, and TPGS released from NPs. The TPGS-b-(PCL-ran-PGA) NPs could function as multifunctional carrier for chemotherapeutic drugs and genetic material delivery, and offer considerable potential as an ideal candidate for in vivo cancer therapy. PMID:23216701

Qiu, Bo; Ji, Minghui; Song, Xiaosong; Zhu, Yongqiang; Wang, Zhongyuan; Zhang, Xudong; Wu, Shu; Chen, Hongbo; Mei, Lin; Zheng, Yi

2012-12-06

199

Co-delivery of docetaxel and endostatin by a biodegradable nanoparticle for the synergistic treatment of cervical cancer  

PubMed Central

Cervical cancer remains a major problem in women's health worldwide. In this research, a novel biodegradable d-?-tocopheryl polyethylene glycol 1000 succinate-b-poly(?-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was developed as a co-delivery system of docetaxel and endostatin for the synergistic treatment of cervical cancer. Docetaxel-loaded TPGS-b-(PCL-ran-PGA) NPs were prepared and further modified by polyethyleneimine for coating plasmid pShuttle2-endostatin. All NPs were characterized in size, surface charge, morphology, and in vitro release of docetaxel and pDNA. The uptake of coumarin 6-loaded TPGS-b-(PCL-ran-PGA)/PEI-pDsRED by HeLa cells was observed via fluorescent microscopy and confocal laser scanning microscopy. Endostatin expression in HeLa cells transfected by TPGS-b-(PCL-ran-PGA)/PEI-pShuttle2-endostatin NPs was detected using Western blot analysis, and the cell viability of different NP-treated HeLa cells was determined by MTT assay. The HeLa cells from the tumor model, nude mice, were treated with various NPs including docetaxel-loaded-TPGS-b-(PCL-ran-PGA)/PEI-endostatin NPs, and their survival time, tumor volume and body weight were monitored during regimen process. The tumor tissue histopathology was analyzed using hematoxylin and eosin staining, and microvessel density in tumor tissue was evaluated immunohistochemically. The results showed that the TPGS-b-(PCL-ran-PGA)/PEI NPs can efficiently and simultaneously deliver both coumarin-6 and plasmids into HeLa cells, and the expression of endostatin was verified via Western blot analysis. Compared with control groups, the TPGS-b-(PCL-ran-PGA)/PEI-pShuttle2-endostatin NPs significantly decreased the cell viability of HeLa cells (p < 0.01), inhibited the growth of tumors, and even eradicated the tumors. The underlying mechanism is attributed to synergistic anti-tumor effects by the combined use of docetaxel, endostatin, and TPGS released from NPs. The TPGS-b-(PCL-ran-PGA) NPs could function as multifunctional carrier for chemotherapeutic drugs and genetic material delivery, and offer considerable potential as an ideal candidate for in vivo cancer therapy.

2012-01-01

200

Co-delivery of docetaxel and endostatin by a biodegradable nanoparticle for the synergistic treatment of cervical cancer  

NASA Astrophysics Data System (ADS)

Cervical cancer remains a major problem in women's health worldwide. In this research, a novel biodegradable d-?-tocopheryl polyethylene glycol 1000 succinate- b-poly(?-caprolactone- ran-glycolide) (TPGS- b-(PCL- ran-PGA)) nanoparticle (NP) was developed as a co-delivery system of docetaxel and endostatin for the synergistic treatment of cervical cancer. Docetaxel-loaded TPGS- b-(PCL- ran-PGA) NPs were prepared and further modified by polyethyleneimine for coating plasmid pShuttle2-endostatin. All NPs were characterized in size, surface charge, morphology, and in vitro release of docetaxel and pDNA. The uptake of coumarin 6-loaded TPGS- b-(PCL- ran-PGA)/PEI-pDsRED by HeLa cells was observed via fluorescent microscopy and confocal laser scanning microscopy. Endostatin expression in HeLa cells transfected by TPGS- b-(PCL- ran-PGA)/PEI-pShuttle2-endostatin NPs was detected using Western blot analysis, and the cell viability of different NP-treated HeLa cells was determined by MTT assay. The HeLa cells from the tumor model, nude mice, were treated with various NPs including docetaxel-loaded-TPGS- b-(PCL- ran-PGA)/PEI-endostatin NPs, and their survival time, tumor volume and body weight were monitored during regimen process. The tumor tissue histopathology was analyzed using hematoxylin and eosin staining, and microvessel density in tumor tissue was evaluated immunohistochemically. The results showed that the TPGS- b-(PCL- ran-PGA)/PEI NPs can efficiently and simultaneously deliver both coumarin-6 and plasmids into HeLa cells, and the expression of endostatin was verified via Western blot analysis. Compared with control groups, the TPGS- b-(PCL- ran-PGA)/PEI-pShuttle2-endostatin NPs significantly decreased the cell viability of HeLa cells ( p < 0.01), inhibited the growth of tumors, and even eradicated the tumors. The underlying mechanism is attributed to synergistic anti-tumor effects by the combined use of docetaxel, endostatin, and TPGS released from NPs. The TPGS- b-(PCL- ran-PGA) NPs could function as multifunctional carrier for chemotherapeutic drugs and genetic material delivery, and offer considerable potential as an ideal candidate for in vivo cancer therapy.

Qiu, Bo; Ji, Minghui; Song, Xiaosong; Zhu, Yongqiang; Wang, Zhongyuan; Zhang, Xudong; Wu, Shu; Chen, Hongbo; Mei, Lin; Zheng, Yi

2012-12-01

201

A fully electronic intensity-modulated radiation therapy quality assurance (IMRT QA) process implemented in a network comprised of independent treatment planning, record and verify, and delivery systems  

PubMed Central

Background The purpose of this study is to implement an electronic method to perform and analyze intensity-modulated radiation therapy quality assurance (IMRT QA) using an aSi megavoltage electronic portal imaging device in a network comprised of independent treatment planning, record and verify (R&V), and delivery systems. Methods A verification plan was generated in the treatment planning system using the actual treatment plan of a patient. After exporting the treatment fields to the R&V system, the fields were delivered in QA mode with the aSi imager deployed. The resulting dosimetric images are automatically stored in a DICOM-RT format in the delivery system treatment console computer. The relative dose density images are subsequently pushed to the R&V system. The absolute dose images are then transferred electronically from the treatment console computer to the treatment planning system and imported into the verification plan in the dosimetry work space for further analysis. Screen shots of the gamma evaluation and isodose comparison are imported into the R&V system as an electronic file (e.g. PDF) to be reviewed prior to initiation of patient treatment. A relative dose image predicted by the treatment planning system can also be sent to the R&V system to be compared with the relative dose density image measured with the aSi imager. Results Our department does not have integrated planning, R&V, and delivery systems. In spite of this, we are able to fully implement a paperless and filmless IMRT QA process, allowing subsequent analysis and approval to be more efficient, while the QA document is directly attached to its specific patient chart in the R&V system in electronic form. The calculated and measured relative dose images can be compared electronically within the R&V system to analyze the density differences and ensure proper dose delivery to patients. Conclusions In the absence of an integrated planning, verifying, and delivery system, we have shown that it is nevertheless possible to develop a completely electronic IMRT QA process.

Bailey, Daniel W; Kumaraswamy, Lalith; Podgorsak, Matthew B

2010-01-01

202

Dosimetric verification and clinical evaluation of a new commercially available Monte Carlo-based dose algorithm for application in stereotactic body radiation therapy (SBRT) treatment planning  

Microsoft Academic Search

Modern cancer treatment techniques, such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT), have greatly increased the demand for more accurate treatment planning (structure definition, dose calculation, etc) and dose delivery. The ability to use fast and accurate Monte Carlo (MC)-based dose calculations within a commercial treatment planning system (TPS) in the clinical setting is now becoming

Margarida Fragoso; Ning Wen; Sanath Kumar; Dezhi Liu; Samuel Ryu; Benjamin Movsas; Ajlouni Munther; Indrin J. Chetty

2010-01-01

203

Severe primary postpartum hemorrhage due to genital tract laceration after operative vaginal delivery: successful treatment with transcatheter arterial embolization  

Microsoft Academic Search

The purpose of this study was to report our experience in the management of severe primary postpartum hemorrhage due to genital\\u000a tract laceration following operative vaginal delivery with forceps using pelvic transcatheter arterial embolization (TAE).\\u000a Ten women (mean age, 31.9 years) with severe primary postpartum hemorrhage due to genital tract laceration after operative\\u000a delivery with forceps were treated with TAE. TAE

Yann Fargeaudou; Philippe Soyer; Olivier Morel; Marc Sirol; Olivier le Dref; Mourad Boudiaf; Henri Dahan; Roland Rymer

2009-01-01

204

Extended Two-Year Results of Radio-Frequency Energy Delivery for the Treatment of Fecal Incontinence (the Secca Procedure)  

Microsoft Academic Search

PURPOSE: This study evaluated the durability and long-term safety of radio-frequency energy delivery for fecal incontinence (Secca procedure). METHODS: This was an extended follow-up of a prospective study in which patients with fecal incontinence of various causes underwent radio-frequency energy delivery to the anal canal muscle. The Cleveland Clinic Florida Fecal Incontinence Scale (0–20), fecal incontinence–related quality-of-life score, and Medical

Takeshi Takahashi; Sandra Garcia-Osogobio; Miguel A. Valdovinos; Carlos Belmonte; Camilo Barreto; Liliana Velasco

2003-01-01

205

Prediction of convection-enhanced drug delivery to the human brain  

Microsoft Academic Search

The treatment for many neurodegenerative diseases of the central nervous system (CNS) involves the delivery of large molecular weight drugs to the brain. The blood brain barrier, however, prevents many therapeutic molecules from entering the CNS. Despite much effort in studying drug dispersion with animal models, accurate drug targeting in humans remains a challenge. This article proposes an engineering approach

Andreas A. Linninger; Mahadevabharath R. Somayaji; Megan Mekarski; Libin Zhang

2008-01-01

206

Treatment planning and delivery evaluation of volumetric modulated arc therapy for stereotactic body radiotherapy of spinal tumours: impact of arc discretization in planning system.  

PubMed

The purpose of this study was to compare single arc volumetric modulated arc therapy (VMAT) to intensity modulated radiotherapy (IMRT) for spine SBRT in terms of target coverage, organ at risk (OAR) sparing and delivery performance. VMAT plans with 91 control points (VMAT-91CP) were generated for 15 spine metastases patients previously treated with a nine-field IMRT technique. VMAT and IMRT plans were compared based on target coverage, maximum spinal cord dose, maximum plan dose and volume of normal tissue receiving 20% to 80% of the prescribed dose. Treatment delivery time and monitor units (MU) were measured to determine delivery efficiency. To assess the impact of arc discretization in the treatment planning system (TPS), the VMAT-91CP plans were modified by almost doubling the number of CPs (VMAT-181CP). Planned-to-delivered dose agreement for both techniques was assessed using two types of 3D detector arrays.VMAT-91CP target coverage was equivalent to IMRT while maintaining or improving spinal cord sparing. This was achieved without increasing the volume of normal tissue receiving low or intermediate dose levels. Planned-to-delivered dose agreement equivalent to IMRT was achieved with VMAT, but required decreasing the CP angular spacing from 4° to 2° (VMAT-181CP plans). On average, VMAT-181CP plans reduced delivery time by 53% compared to IMRT. Single-arc VMAT for spine SBRT improved delivery efficiency while maintaining target coverage and OAR sparing compared to IMRT. VMAT plans generated with a CP gantry angular spacing of 2° is recommended to avoid a discretization effect in the TPS and ensure acceptable planned-to-delivered dose agreement. PMID:22712602

Marchand, E L; Sahgal, A; Zhang, T J; Millar, B A; Sharpe, M; Moseley, D; Letourneau, D

2012-06-15

207

Targeted and intracellular triggered delivery of therapeutics to cancer cells and the tumor microenvironment: impact on the treatment of breast cancer  

Microsoft Academic Search

Limiting tumor invasion to the surrounding healthy tissues has proven to be clinically relevant for anticancer treatment options.\\u000a We have demonstrated that, within a solid tumor, it is possible to achieve such a goal with the same nanoparticle by intracellular\\u000a and triggered targeted drug delivery to more than one cell population. We have identified the nucleolin receptor in endothelial\\u000a and

Vera Moura; Manuela Lacerda; Paulo Figueiredo; Maria L. Corvo; Maria E. M. Cruz; Raquel Soares; Maria C. Pedroso de Lima; Sérgio Simões; João N. Moreira

208

An acetylated polysaccharide-PTFE membrane-covered stent for the delivery of gemcitabine for treatment of gastrointestinal cancer and related stenosis  

Microsoft Academic Search

Gemcitabine (Gem) eluting metal stents were prepared for potential application as drug delivery systems for localized treatment of malignant tumors. Pullulan, a natural polysaccharide, was chemically acetylated (pullulan acetate; PA) by different degrees (1.18, 1.71, and 2.10 acetyl groups per glucose unit of pullulan), layered on polytetrafluoroethylene (PTFE), and applied as part of a Gem-loaded controlled-release membrane for drug-eluting non-vascular

Sumi Moon; Su-Geun Yang; Kun Na

2011-01-01

209

Efficacy of a portable oxygen concentrator with pulsed delivery for treatment of hypoxemia during anesthesia of wildlife.  

PubMed

Portable battery-driven oxygen concentrators provide an alternative to the use of oxygen cylinders for treatment of hypoxemia during field anesthesia. The aim of this study was to evaluate the use of the EverGo Portable Oxygen Concentrator (Respironics, Murrysville, Pennsylvania 15668, USA) with pulse-dose delivery for improvement of arterial oxygenation during anesthesia of wildlife. This concentrator delivers oxygen in a pulsed flow with pulse volumes from 12 to 70 ml, up to a maximum capacity of 1.05 L/min. The pulse-dose setting shall be adjusted according to the respiratory rate of the animal, e.g., setting 6 for a respiratory rate < or = 15/min. The study included 16 free-ranging brown bears (Ursus arctos), 18 free-ranging bighorn sheep (Ovis canadensis), and five captive reindeer (Rangifer tarandus). Oxygen was administered via two nasal lines that were inserted through the nostrils to the level of the medial canthus of the eyes. Arterial blood samples were collected before, during, and after oxygen therapy and immediately analyzed. When providing oxygen from the portable concentrator, the arterial oxygenation markedly improved in all brown bears and some reindeer, whereas no or minor improvement was seen in the bighorn sheep. The mean +/- SD (range) PaO2 during oxygen supplementation was 134 +/- 29 (90-185) mmHg in the brown bears, 52 +/- 11 (32-67) mmHg in the bighorn sheep, and 79 +/- 19 (61-110) mmHg in the reindeer. The efficacy of the evaluated method may be influenced by ambient temperature, altitude, pulse-dose setting on the concentrator, the animal's respiratory rate, and species-specific physiology during anesthesia. Advantages of the portable oxygen concentrator included small size and low weight, ease of operate, and rechargeablity. PMID:22448511

Fahlman, Asa; Caulkett, Nigel; Arnemo, Jon M; Neuhaus, Peter; Ruckstuhl, Kathreen E

2012-03-01

210

Cetuximab conjugated vitamin E TPGS micelles for targeted delivery of docetaxel for treatment of triple negative breast cancers.  

PubMed

We developed a system of Cetuximab-conjugated micelles of vitamin E TPGS for targeted delivery of docetaxel as a model anticancer drug for treatment of the triple negative breast cancer (TNBC), which shows no expression of either one of the hormone progesterone receptor (PR), estrogen receptor (ER) and epidermal growth factor receptor 2 (HER2) and is thus more difficult to be treated than the positive breast cancer. Such micelles are of desired particle size, drug loading, drug encapsulation efficiency and drug release profile. Their surface morphology, surface charge and surface chemistry were also characterized. The fibroblast cells (NIH3T3), HER2 overexpressed breast cancer cells (SK-BR-3), ER and PR overexpressed breast cancer cells (MCF7), and TNBC cells of high, moderate and low EGFR expression (MDA MB 468, MDA MB 231 and HCC38) were employed to access in vitro cellular uptake of the coumarin 6 loaded TPGS micelles and cytotoxicity of docetaxel formulated in the micelles. The high IC50 value, which is the drug concentration needed to kill 50% of the cells in a designated period such as 24 h, obtained from Taxotere(®) showed that the TNBC cells are indeed more resistant to the free drug than the positive breast cancer cells. However, the therapeutic effects of docetaxel could be greatly enhanced by the formulation of Cetuximab conjugated TPGS micelles, which demonstrated 205.6 and 223.8 fold higher efficiency than Taxotere(®) for the MDA MB 468 and MDA MB 231 cell lines respectively. PMID:24090836

Kutty, Rajaletchumy Veloo; Feng, Si-Shen

2013-10-03

211

Grading More Accurately  

ERIC Educational Resources Information Center

|Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…

Rom, Mark Carl

2011-01-01

212

Positive, accurate animal identification  

Microsoft Academic Search

Positive, accurate identification of animals and their products would be very helpful in livestock commerce, prevention of theft and fraud and in tracing animals and products to origin. Food safety, animal health, and prevention of epidemics, would be enhanced by combining identification with location. Identification may be by electronic chips, iris or retinal scans, antibody or DNA analysis. A cross

Philip Dziuk

2003-01-01

213

Systemic delivery of AAV8 in utero results in gene expression in diaphragm and limb muscle: Treatment implications for muscle disorders  

PubMed Central

One of the major challenges in the treatment of primary muscle disorders, which often affect many muscle groups, is achieving efficient, widespread transgene expression in muscle. In utero gene transfer can potentially address this problem by accomplishing gene delivery when the tissue mass is small and the immune system is immature. Previous studies with systemic in utero adeno-associated viral (AAV) vector serotype 1 gene delivery to embryonic day 16 (E-16) pups resulted in high levels of transduction in diaphragm and intercostal muscles, but no detectable transgene expression in limb muscles. Recently newer AAV serotypes such as AAV8 have demonstrated widespread and high transgene expression in skeletal muscles and diaphragm by systemic delivery in adult and neonatal mice. We tested AAV8 vector gene delivery by intraperitoneal administration in E-16 mice in utero. Using an AAV8 vector carrying a lacZ reporter gene, we observed high level transduction of diaphragm and intercostal muscles and more moderate transduction of multiple limb muscles and heart. Our current studies demonstrate the potential of AAV8 to achieve widespread muscle transduction in utero and suggest its therapeutic potential for primary muscle disorders.

Koppanati, Bhanu Munil; Li, Juan; Xiao, Xiao; Clemens, Paula R.

2009-01-01

214

Oral delivery of oil-based formulation for a novel synthetic cationic peptide of GnRH (gonadotropin-releasing hormone) antagonist for prostate cancer treatment.  

PubMed

LXT-101, a cationic peptide is a novel antagonist of gonadotropin-releasing hormone (GnRH) for prostate cancer treatment. However, effective delivery of peptide drugs into the body by the oral route remains a major challenge due to their origin properties with high molecular weights, strong polarity and low stability in the gastrointestinal (GI) tract. In this study, we have developed a novel oral delivery of oil-based formulation in which therapeutic peptide LXT-101 are solubilized in oils and with this solution as oil phase, an optimum formulation of self-microemulsifying drug delivery system (SMEDDS) was developed. The peptide stability with the SMEDDS formulation in artificial gastric and intestinal fluid was tested in vitro. On the other hand, the testosterone level and plasma concentration of LXT-101 in rats after oral administration of the SMEDDS formulation were investigated in vivo. The data in vitro indicated that LXT-101 in the SMEDDS formulation was stable over 8 h in artificial gastric and intestinal fluid. LXT-101 can be absorbed in vivo and suppression of testosterone maintained in castration level within 12 h can be achieved effectively after SMEDDS formulation administered orally at a dose of 3.5 mg/kg. The approach can provide a potential way for delivery peptides by oral. PMID:23623791

Zhang, Guiying; Wang, Tao; Gao, Lijun; Quan, Dongqin

2013-04-24

215

Microencapsulation: A promising technique for controlled drug delivery  

PubMed Central

Microparticles offer various significant advantages as drug delivery systems, including: (i) an effective protection of the encapsulated active agent against (e.g. enzymatic) degradation, (ii) the possibility to accurately control the release rate of the incorporated drug over periods of hours to months, (iii) an easy administration (compared to alternative parenteral controlled release dosage forms, such as macro-sized implants), and (iv) Desired, pre-programmed drug release profiles can be provided which match the therapeutic needs of the patient. This article gives an overview on the general aspects and recent advances in drug-loaded microparticles to improve the efficiency of various medical treatments. An appropriately designed controlled release drug delivery system can be a foot ahead towards solving problems concerning to the targeting of drug to a specific organ or tissue, and controlling the rate of drug delivery to the target site. The development of oral controlled release systems has been a challenge to formulation scientist due to their inability to restrain and localize the system at targeted areas of gastrointestinal tract. Microparticulate drug delivery systems are an interesting and promising option when developing an oral controlled release system. The objective of this paper is to take a closer look at microparticles as drug delivery devices for increasing efficiency of drug delivery, improving the release profile and drug targeting. In order to appreciate the application possibilities of microcapsules in drug delivery, some fundamental aspects are briefly reviewed.

Singh, M.N.; Hemant, K.S.Y.; Ram, M.; Shivakumar, H.G.

2010-01-01

216

Long-wave explicit and Short-wave implicit (LESI) treatment of the barotropic mode to accurately calculate slow modes in ocean models  

NASA Astrophysics Data System (ADS)

Many ocean models are primarily concerned with calculating currents of slowly propagating modes that are dynamically associated with buoyancy, Coriolis, field accelerations, and slowly-varying forcing. Calculating such slow modes involves adjustments by the very much faster barotropic mode. In order to minimize the computational cost, two approaches are commonly used. The split-explicit method solves for both fast and slow modes explicitly but with different time steps. The semi-implicit method uses the same time step for fast and slow modes but treats the fast barotropic waves implicitly and the slow modes explicitly. The present work demonstrates a refinement to the semi-implicit method. Weighted Jacobi iterations are used to low-pass filter the fast barotropic mode so that long wavelengths can be treated explicitly. The short-wave part of the fast barotopic mode is still treated implicitly. Damping of the fast barotropic modes is less severe than for the corresponding implicit calculation. Importantly, tests show that a slow internal wave is accurately modelled and the solution is stable, even with the addition of barotropic noise. The method is demonstrated using a three-dimensional model of a lagoon system.

Sanderson, Brian G.

217

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation  

PubMed Central

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

Burke, Caitlin W.; Price, Richard J.

2010-01-01

218

Breech delivery.  

PubMed

Fetuses that present by the breech are at increased risk of trauma and hypoxia during delivery. The threshold for Caesarean section for breech presentation had been low for several years. The result of the term breech trial confirms that planned Caesarean section is the best method of delivering the singleton frank or complete breech at term. The best mode of delivery for the pre-term breech is less clear. Vaginal breech delivery will be unavoidable in certain circumstances and it is therefore important to be adept with the techniques of vaginal breech delivery. The atraumatic technique of delivery of the baby presenting by the breech at times of Caesarean section is similar to that of assisted vaginal breech delivery. The number of vaginal breech deliveries is falling, and regular teaching using video clips or practising with mannequins will be necessary to preserve the skills of vaginal breech delivery. PMID:11866495

Mukhopadhyay, Sambit; Arulkumaran, Sabaratnam

2002-02-01

219

Accurate Unlexicalized Parsing  

Microsoft Academic Search

We demonstrate that an unlexicalized PCFG can parse much more accurately than previously shown, by making use of simple, linguistically motivated state splits, which break down false independence assumptions latent in a vanilla treebank grammar. Indeed, its performance of 86.36% (LP\\/LR F PCFG models, and surprisingly close to the current state-of-the-art. This result has potential uses beyond establishing a strong

Dan Klein; Christopher D. Manning

2003-01-01

220

Motivational Enhancement Therapy Coupled with Cognitive Behavioral Therapy versus Brief Advice; A Randomized Trial for Treatment of Hazardous Substance Use in Pregnancy and After Delivery  

PubMed Central

Objective To compare the efficacy of motivational enhancement therapy coupled with cognitive behavioral therapy (MET-CBT) to brief advice for treatment of substance use in pregnancy. Method This was a randomized, parallel, controlled trial that was yoked to prenatal care and delivered at hospital outpatient clinics. We enrolled 168 substance using women who had not yet completed an estimated 28 weeks of pregnancy. Obstetrical clinicians provided brief advice and study nurses administered manualized MET-CBT. The primary outcome was percentage of days in the prior 28 days, that alcohol and/or drugs were used immediately before and three months post delivery. Results There were no significant differences across groups in terms of self-reported percentage of days that drugs or alcohol were used prior to and three months post delivery. Biological measures showed similar results. There was a trend (p=0.08) for lower risk of preterm birth among those who received MET-CBT. Conclusions The tested interventions had similar therapeutic effects. Hence, both treatments may be suitable for pregnant substance users, depending on the population, setting, and provider availability. Interventions that are intensified after delivery may decrease postpartum ‘rebound’ effects in substance misuse.

Yonkers, Kimberly A.; Forray, Ariadna; Howell, Heather B.; Gotman, Nathan; Kershaw, Trace; Rounsaville, Bruce J.; Carroll, Kathleen M.

2012-01-01

221

Quality assurance of serial tomotherapy for head and neck patient treatments  

Microsoft Academic Search

Purpose: A commercial serial tomotherapy intensity-modulated radiation therapy (IMRT) treatment planning (Peacock, NOMOS Corp., Sewickley, PA) and delivery system is in clinical use. The dose distributions are highly conformal, with large dose gradients often surrounding critical structures, and require accurate localization and dose delivery. Accelerator and patient-specific quality assurance (QA) procedures have been developed that address the localization, normalization, and

Daniel A Low; K. S. Clifford Chao; Sasa Mutic; Russell L Gerber; Carlos A Perez; James A Purdy

1998-01-01

222

Molecular Bacterial Load Assay, a Culture-Free Biomarker for Rapid and Accurate Quantification of Sputum Mycobacterium tuberculosis Bacillary Load during Treatment ? #  

PubMed Central

A molecular assay to quantify Mycobacterium tuberculosis is described. In vitro, 98% (n = 96) of sputum samples with a known number of bacilli (107 to 102 bacilli) could be enumerated within 0.5 log10. In comparison to culture, the molecular bacterial load (MBL) assay is unaffected by other microorganisms present in the sample, results are obtained more quickly (within 24 h) and are seldom inhibited (0.7% samples), and the MBL assay critically shows the same biphasic decline as observed longitudinally during treatment. As a biomarker of treatment response, the MBL assay responds rapidly, with a mean decline in bacterial load for 111 subjects of 0.99 log10 (95% confidence interval [95% CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant association between the rate of bacterial decline during the same 3 days and bacilli ml?1 sputum at day 0 (linear regression, P = 0.0003) and a 3.62 increased odds ratio of relapse for every 1 log10 increase in pretreatment bacterial load (95% CI, 1.53 to 8.59).

Honeyborne, Isobella; McHugh, Timothy D.; Phillips, Patrick P. J.; Bannoo, Selina; Bateson, Anna; Carroll, Nora; Perrin, Felicity M.; Ronacher, Katharina; Wright, Laura; van Helden, Paul D.; Walzl, Gerhard; Gillespie, Stephen H.

2011-01-01

223

Explaining Glaciers, Accurately  

NSDL National Science Digital Library

What happens when a geology graduate student and two fourth-grade teachers collaborate on lessons for the classroom? They discover interesting and practical ways to explore geology and other scientific concepts, that's what! Here they share the glacial erosion lessons that grew out of the geologist's frustration at finding glacial erosion labs erroneously showing glaciers eroding by pushing rocks. Their goal was to find a way to show and explain glacial erosion more accurately and in a way that elementary age students could understand.

Tate, Mari; Faw, Mary; Scott, Nancy

2009-04-01

224

Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery  

PubMed Central

Background In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients. Study design Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events. Results Chemotherapy delivery was suboptimal (with a relative dose intensity ? 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis. Conclusions In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.

2010-01-01

225

Development and testing of gold nanoparticles for drug delivery and treatment of heart failure: a theranostic potential for PPP cardiology  

PubMed Central

Introduction Nanoscale gold particles (AuNPs) have wide perspectives for biomedical applications because of their unique biological properties, as antioxidative activity and potentials for drug delivery. Aims and objectives The aim was to test effects of AuNPs using suggested heart failure rat model to compare with proved medication Simdax, to test gold nanoparticle for drug delivery, and to test sonoporation effect to increase nanoparticles delivery into myocardial cells. Material and methods We performed biosafety and biocompatibility tests for AuNPs and conjugate with Simdax. For in vivo tests, we included Wistar rats weighing 180–200 g (n = 54), received doxorubicin in cumulative dose of 12.0 mg/kg to model advance heart failure, registered by ultrasonography. We formed six groups: the first three groups of animals received, respectively, 0.06 ml Simdax, AuNPs, and conjugate (AuNPs-Simdax), intrapleurally, and the second three received them intravenously. The seventh group was control (saline). We performed dynamic assessment of heart failure regression in vivo measuring hydrothorax. Sonoporation of gold nanoparticles to cardiomyocytes was tested. Results We designed and constructed colloidal, spherical gold nanoparticles, AuNPs-Simdax conjugate, both founded biosafety (in cytotoxicity, genotoxicity, and immunoreactivity). In all animals of the six groups after the third day post-medication injection, no ascites and liver enlargement were registered (P < 0.001 vs controls). Conjugate injection showed significantly higher hydrothorax reduction than Simdax injection only (P < 0.01); gold nanoparticle injection showed significantly higher results than Simdax injection (P < 0.05). AuNPs and conjugate showed no significant difference for rat recovery. Difference in rat life continuity was significant between Simdax vs AuNPs (P < 0.05) and Simdax vs conjugate (P < 0.05). Sonoporation enhances AuNP transfer into the cell and mitochondria that were highly localized, superior to controls (P < 0.01 for both). Conclusions Gold nanoparticles of 30 nm and its AuNPs-Simdax conjugate gave positive results in biosafety and biocompatibility in vitro and in vivo. AuNPs-Simdax and AuNPs have similar significant cardioprotective effects in rats with doxorubicin-induced heart failure, higher than that of Simdax. Intrapleural (local) delivery is preferred over intravenous (systemic) delivery according to all tested parameters. Sonoporation is able to enhance gold nanoparticle delivery to myocardial cells in vivo.

2013-01-01

226

Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery.  

PubMed

Cilengitide is a cyclic pentapeptide that is a specific inhibitor of the ?v?3 and ?v?5 integrins. Preclinical studies demonstrate antiangiogenic activity and anti-invasive activity in a number of glioma models. This study was designed to evaluate the efficacy and tumor delivery of cilengitide in patients with recurrent glioblastoma. Patients with recurrent glioblastoma who require a surgical resection for optimal clinical care received 3 intravenous doses of cilengitide at either 500 or 2000 mg (day -8, -4, -1) prior to undergoing tumor resection with corresponding blood samples for plasma to tumor comparisons. After recovery from surgery, patients were treated with cilengitide (2000 mg i.v. twice weekly, maximum of 2 years of treatment). The study accrued 30 patients with recurrent glioblastoma, 26 were evaluable for efficacy. The 6-month progression free survival rate was 12%. Cilengitide was detected in all tumor specimens with higher levels in the group receiving 2000 mg dosing while corresponding plasma concentrations were low, often below the lower limit of detection. These results confirm drug delivery and possibly retention in tumor. This study provides evidence that with established dosing, cilengitide is adequately delivered to the tumor, although as a single agent, efficacy in recurrent glioblastoma is modest. However, these results demonstrating drug delivery to tumor do support continued investigation of this agent as preliminary results from recent studies combining cilengitide with cytotoxic therapies are promising. PMID:21739168

Gilbert, Mark R; Kuhn, John; Lamborn, Kathleen R; Lieberman, Frank; Wen, Patrick Y; Mehta, Minesh; Cloughesy, Timothy; Lassman, Andrew B; Deangelis, Lisa M; Chang, Susan; Prados, Michael

2011-07-08

227

Women and Heart Disease - Physiologic Regulation of Gene Delivery and Expression: Bioreducible Polymers and Ischemia-Inducible Gene Therapies for the Treatment of Ischemic Heart Disease  

PubMed Central

Ischemic heart disease (IHD) is the leading cause of death in the United States today. This year over 750,000 women will have a new or recurrent myocardial infarction. Currently, the mainstay of therapy for IHD is revascularization. Increasing evidence, however, suggests that revascularization alone is insufficient for the longer-term management of many patients with IHD. To address these issues, innovative therapies that extend beyond revascularization to protection of the myocyte and preservation of ventricular function are required. The emergence of gene therapy and proteomics offers the potential for innovative prophylactic and treatment strategies for IHD. The goal of our research is to develop therapeutic gene constructs for the treatment of myocardial ischemia that are clinically safe and effective. Toward this end, we describe the development of physiologic regulation of gene delivery and expression using bioreducible polymers and ischemia-inducible gene therapies for the potential treatment of ischemic heart disease in women.

Yockman, James W.; Bull, David A.

2009-01-01

228

Accurate measurement of time  

NASA Astrophysics Data System (ADS)

The paper discusses current methods for accurate measurements of time by conventional atomic clocks, with particular attention given to the principles of operation of atomic-beam frequency standards, atomic hydrogen masers, and atomic fountain and to the potential use of strings of trapped mercury ions as a time device more stable than conventional atomic clocks. The areas of application of the ultraprecise and ultrastable time-measuring devices that tax the capacity of modern atomic clocks include radio astronomy and tests of relativity. The paper also discusses practical applications of ultraprecise clocks, such as navigation of space vehicles and pinpointing the exact position of ships and other objects on earth using the GPS.

Itano, Wayne M.; Ramsey, Norman F.

1993-07-01

229

Nanoclays for polymer nanocomposites, paints, inks, greases and cosmetics formulations, drug delivery vehicle and waste water treatment  

Microsoft Academic Search

An overview of nanoclays or organically modified layered silicates (organoclays) is presented with emphasis placed on the\\u000a use of nanoclays as the reinforcement phase in polymer matrices for preparation of polymer\\/layered silicates nanocomposites,\\u000a rheological modifier for paints, inks and greases, drug delivery vehicle for controlled release of therapeutic agents, and\\u000a nanoclays for industrial waste water as well as potable water

Hasmukh A. Patel; Rajesh S. Somani; Hari C. Bajaj; Raksh V. Jasra

2006-01-01

230

Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment  

Microsoft Academic Search

Catheter-based local delivery of biodegradable nanoparticles (NP) with sustained release characteristics represents a therapeutic approach to reduce restenosis. Paclitaxel-loaded NP consisting of poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) (PVA-g-PLGA) with varying PLGA chain length as well as poly(lactide-co-glycolide) (PLGA), were prepared by a solvent evaporation technique. NP of <180 nm in diameter characterized by photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and atomic force

Ulrich Westedt; Marc Kalinowski; Matthias Wittmar; Thomas Merdan; Florian Unger; Jutta Fuchs; Susann Schäller; Udo Bakowsky; Thomas Kissel

2007-01-01

231

Combined therapy with human cord blood cell transplantation and basic fibroblast growth factor delivery for treatment of myocardial infarction  

Microsoft Academic Search

Background: Transplanting cord blood-derived cells has been shown to augment neovascularization in ischaemic tissue. Aim: To test whether sustained delivery of basic fibroblast growth factor (bFGF) enhances the efficacy of angiogenic cord blood mononuclear cell (CBMNC) transplantation therapy in treating myocardial infarction. Methods: Three weeks after myocardial infarction, Sprague-Dawley rats were randomised to either injection of medium only (control), CBMNC

Seung-Woo Cho; Il-Kwon Kim; Suk Ho Bhang; Boyoung Joung; Young Jin Kim; Kyung Jong Yoo; Yoon-Sun Yang; Cha Yong Choi; Byung-Soo Kim

232

Treatment of postoperative nausea and vomiting after spinal anesthesia for cesarean delivery: A randomized, double-blinded comparison of midazolam, ondansetron, and a combination  

PubMed Central

Background: The antiemetic efficacy of midazolam and ondansetron was shown before. The aim of the present study was to compare efficacy of using intravenous midazoalm, ondansetron, and midazolam in combination with ondansetron for treatment of nausea and vomiting after cesarean delivery in parturient underwent spinal anesthesia. Materials and Methods: One hundred thirty two parturients were randomly allocated to one of three groups: group M (n = 44) that received intravenous midazoalm 30 ?g/kg; group O (n = 44) that received intravenous ondansetron 8 mg; group MO (n = 44) that received intravenous midazoalm 30 ?g/kg combined with intravenous ondansetron 8 mg if patients had vomiting or VAS of nausea ? 3 during surgery (after umbilical cord clamping) and 24 hours after that. The incidence and severity of vomiting episodes and nausea with visual analog scale (VAS) > 3 were evaluated at 2 hours, 6 hours, and 24 hours after injection of study drugs. Results: The incidence of nausea was significantly less in group MO compared with group M and group O at 6 hours postoperatively (P = 0.01). This variable was not significantly different in three groups at 2 hours and 24 hours after operation. The severity of nausea and vomiting was significantly different in three groups at 6 hours after operation (P < 0.05). Conclusion: Our study showed that using intravenous midazolam 30 ?g/kg in combination with intravenous ondansetron 8 mg was superior to administering single drug in treatment of emetic symptoms after cesarean delivery under spinal anesthesia.

Jabalameli, Mitra; Honarmand, Azim; Safavi, Mohammadreza; Chitsaz, Mohsen

2012-01-01

233

Enhanced delivery of topically-applied formulations following skin pre-treatment with a hand-applied, plastic microneedle array.  

PubMed

The purpose of this work is to characterize microchannels created by polymeric microneedles, applied by hand, and to demonstrate enhanced delivery of topically applied formulations of lidocaine hydrochloride and methylprednisolone sodium succinate (MPSS). 3M's Microstructured Transdermal System (MTS) arrays were applied to domestic swine to demonstrate reliability of penetration, depth of penetration and durability of the structures to repeat application and high force. Tissue levels of lidocaine and MPSS following topical application with and without microneedle pretreatment were determined by HPLC-MS analysis following digestion of biopsies. Almost all microneedles penetrate the stratum corneum upon hand force application. The depth of penetration varies from <100µm to nearly 150µm depending on the application force and the firmness of the underlying tissue. The arrays show excellent durability to repeated in-vivo application, with less than 5% of the structures evidencing even minimal tip bending after 16 applications. Under extreme force against a rigid surface, the microneedles bend but do not break. A lidocaine hydrochloride formulation applied topically in-vivo showed ~340% increase in local tissue levels when the MTS arrays were used to twice pre-treat the skin prior to applying the drug. Local delivery of a topically applied formulation of MPSS was over one order of magnitude higher when the application site was twice pre-treated with the MTS array. 3M's MTS array (marketed as 3M(TM) Microchannel Skin System) provides repeatable and robust penetration of the stratum corneum and epidermis and enhances delivery of some formulations such as lidocaine hydrochloride. PMID:21696356

Duan, Dan; Moeckly, Craig; Gysbers, Jerry; Novak, Chris; Prochnow, Gayatri; Siebenaler, Kris; Albers, Leila; Hansen, Kris

2011-09-01

234

Inhalable Antibiotic Delivery Using a Dry Powder Co-delivering Recombinant Deoxyribonuclease and Ciprofloxacin for Treatment of Cystic Fibrosis  

Microsoft Academic Search

Purpose  To achieve efficient antibiotic delivery to the cystic fibrosis (CF) airway using a single inhalable powder co-encapsulating\\u000a a mucolytic and an antibiotic.\\u000a \\u000a \\u000a \\u000a Methods  Inhalable dry powders containing deoxyribonuclease and\\/or ciprofloxacin (DNase, Cipro, and DNase\\/Cipro powders) were produced\\u000a by spray-drying with dipalmitylphosphatidylcholine, albumin, and lactose as excipients, and their antibacterial effects were\\u000a evaluated using the artificial sputum model.\\u000a \\u000a \\u000a \\u000a Results  All powders showed mass

Yan Yang; Michael D. Tsifansky; Chia-Jung Wu; Hae In Yang; Gudrun Schmidt; Yoon Yeo

2010-01-01

235

Peptide and protein delivery using new drug delivery systems.  

PubMed

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery. PMID:23662604

Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

236

Phantoms for IMRT Dose Distribution Measurement and Treatment Verification  

Microsoft Academic Search

Background: The verification of intensity-modulated radiation therapy (IMRT) patient treatment dose distributions is currently based on custom-built or modified dose measurement phantoms. The only commercially available IMRT treatment planning and delivery system (Peacock, NOMOS Corp.) is supplied with a film phantom that allows accurate spatial localization of the dose distribution using radiographic film. However, measurements using other dosimeters are necessary

Daniel A Low; Russell L Gerber; Sasa Mutic; James A Purdy

1998-01-01

237

Accurate Optical Reference Catalogs  

NASA Astrophysics Data System (ADS)

Current and near future all-sky astrometric catalogs on the ICRF are reviewed with the emphasis on reference star data at optical wavelengths for user applications. The standard error of a Hipparcos Catalogue star position is now about 15 mas per coordinate. For the Tycho-2 data it is typically 20 to 100 mas, depending on magnitude. The USNO CCD Astrograph Catalog (UCAC) observing program was completed in 2004 and reductions toward the final UCAC3 release are in progress. This all-sky reference catalogue will have positional errors of 15 to 70 mas for stars in the 10 to 16 mag range, with a high degree of completeness. Proper motions for the about 60 million UCAC stars will be derived by combining UCAC astrometry with available early epoch data, including yet unpublished scans of the complete set of AGK2, Hamburg Zone astrograph and USNO Black Birch programs. Accurate positional and proper motion data are combined in the Naval Observatory Merged Astrometric Dataset (NOMAD) which includes Hipparcos, Tycho-2, UCAC2, USNO-B1, NPM+SPM plate scan data for astrometry, and is supplemented by multi-band optical photometry as well as 2MASS near infrared photometry. The Milli-Arcsecond Pathfinder Survey (MAPS) mission is currently being planned at USNO. This is a micro-satellite to obtain 1 mas positions, parallaxes, and 1 mas/yr proper motions for all bright stars down to about 15th magnitude. This program will be supplemented by a ground-based program to reach 18th magnitude on the 5 mas level.

Zacharias, N.

2006-08-01

238

Tumor-targeted Chlorotoxin-coupled Nanoparticles for Nucleic Acid Delivery to Glioblastoma Cells: A Promising System for Glioblastoma Treatment.  

PubMed

The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery of nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), a peptide reported to bind selectively to glioma cells while showing no affinity for non-neoplastic cells, was covalently coupled to liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). The resulting targeted nanoparticles, designated CTX-coupled stable nucleic acid lipid particles (SNALPs), exhibited excellent features for in vivo application, namely small size (<180?nm) and neutral surface charge. Cellular association and internalization studies revealed that attachment of CTX onto the liposomal surface enhanced particle internalization into glioma cells, whereas no significant internalization was observed in noncancer cells. Moreover, nanoparticle-mediated miR-21 silencing in U87 human GBM and GL261 mouse glioma cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Preliminary in vivo studies revealed that CTX enhances particle internalization into established intracranial tumors. Overall, our results indicate that the developed targeted nanoparticles represent a valuable tool for targeted nucleic acid delivery to cancer cells. Combined with a drug-based therapy, nanoparticle-mediated miR-21 silencing constitutes a promising multimodal therapeutic approach towards GBM.Molecular Therapy-Nucleic Acids (2013) 2, e100; doi:10.1038/mtna.2013.30; published online 18 June 2013. PMID:23778499

Costa, Pedro M; Cardoso, Ana L; Mendonça, Liliana S; Serani, Angelo; Custódia, Carlos; Conceição, Mariana; Simões, Sérgio; Moreira, João N; Pereira de Almeida, Luís; Pedroso de Lima, Maria C

2013-06-18

239

A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy  

PubMed Central

Background Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. Methods The capacity of AAV1, AAV6 or AAV8 to cross the vascular endothelial barrier carrying a micro-dystrophin cDNA was compared under identical conditions with delivery through a catheter placed in the femoral artery of the mdx mouse. Transduction efficiency was assessed by immuno-staining using an antibody (Manex1a) that recognizes the N-terminus of micro-dystrophin. The degree of physiologic correction was assessed by measuring tetanic force and protection from eccentric contraction in the extensor digitorum longus muscle (EDL). The vascular delivery paradigm found successful in the mouse was carried to the non-human primate to test its potential translation to boys with DMD. Results Regional vascular delivery resulted in transduction by rAAV8.micro-dystrophin reaching 94.5 ± 0.9 (1 month), 91.3 ± 3.1 (2 months), and 89.6 ± 1.6% (3 months). rAAV6.micro-dystrophin treated animals demonstrated 87.7 ± 6.8 (1 month), 78.9 ± 7.4 (2 months), and 81.2 ± 6.2% (3 months) transduction. In striking contrast, rAAV1 demonstrated very low transduction efficiency [0.9 ± 0.3 (1 month), 2.1 ± 0.8 (2 months), and 2.1 ± 0.7% (3 months)] by vascular delivery. Micro-dystrophin delivered by rAAV8 and rAAV6 through the femoral artery significantly improved tetanic force and protected against eccentric contraction. Mouse studies translated to the hindlimb of cynamologous macaques using a similar vascular delivery paradigm. rAAV8 carrying eGFP in doses proportional to the mouse (5 × 1012 vg/kg in mouse vs 2 × 1012 vg/kg in monkey) demonstrated widespread gene expression [medial gastrocnemius – 63.8 ± 4.9%, lateral gastrocnemius – 66.0 ± 4.5%, EDL – 80.2 ± 3.1%, soleus – 86.4 ± 1.9%, TA – 72.2 ± 4.0%. Conclusion These studies demonstrate regional vascular gene delivery with AAV serotype(s) in mouse and non-human primate at doses, pressures and volumes applicable for clinical trials in children with DMD.

Rodino-Klapac, Louise R; Janssen, Paul ML; Montgomery, Chrystal L; Coley, Brian D; Chicoine, Louis G; Clark, K Reed; Mendell, Jerry R

2007-01-01

240

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases  

Microsoft Academic Search

Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases.

Stephanie H. Kim; Robert J. Lutz; Nam Sun Wang; Michael R. Robinson

2007-01-01

241

The application of electron beam delivery using dose rate variation and dynamic couch motion in conformal treatment of the cranial-spinal axis  

SciTech Connect

Radiation therapy to the cranial-spinal axis is typically targeted to the spinal cord and to the cerebrospinal fluid (CSF) in the subarachnoid space adjacent to the spinal cord and brain. Standard techniques employed in the treatment of the whole central nervous system do little to compensate for the varying depths of spinal cord along the length of the spinal field. Lateral simulation films, sagittal magnetic resonance imaging (MRI), or computerized tomography (CT) are used to estimate an average prescription depth for treatment along the spine field. However, due to the varying depth of the target along the spinal axis, even with the use of physical compensators, there can be considerable dose inhomogeneity along the spine field. With the advent of treatment machines that have full dynamic capabilities, a technique has been devised that will allow for more conformal dose distribution along the full length of the spinal field. This project simulates this technique utilizing computer-controlled couch motion to deliver multiple small electron beams of differing energies and intensities. CT planning determines target depth along the entire spine volume. The ability to conform dose along the complete length of the treatment field is investigated through the application of superpositioning of the fields as energies and intensities change. The positioning of each beam is registered with the treatment couch dynamic motion. This allows for 1 setup in the treatment room rather than multiple setups for each treatment position, which would have been previously required. Dose-volume histograms are utilized to evaluate the dose delivered to structures in the beam exit region. This technique will allow for precise localization and delivery of a homogeneous dose to the entire CSF space.

Chapek, Julie; Watson, Gordon; Smith, Lynn M.; Leavitt, Dennis

2002-12-31

242

The application of electron beam delivery using dose rate variation and dynamic couch motion in conformal treatment of the cranial-spinal axis.  

PubMed

Radiation therapy to the cranial-spinal axis is typically targeted to the spinal cord and to the cerebrospinal fluid (CSF) in the subarachnoid space adjacent to the spinal cord and brain. Standard techniques employed in the treatment of the whole central nervous system do little to compensate for the varying depths of spinal cord along the length of the spinal field. Lateral simulation films, sagittal magnetic resonance imaging (MRI), or computerized tomography (CT) are used to estimate an average prescription depth for treatment along the spine field. However, due to the varying depth of the target along the spinal axis, even with the use of physical compensators, there can be considerable dose inhomogeneity along the spine field. With the advent of treatment machines that have full dynamic capabilities, a technique has been devised that will allow for more conformal dose distribution along the full length of the spinal field. This project simulates this technique utilizing computer-controlled couch motion to deliver multiple small electron beams of differing energies and intensities. CT planning determines target depth along the entire spine volume. The ability to conform dose along the complete length of the treatment field is investigated through the application of superpositioning of the fields as energies and intensities change. The positioning of each beam is registered with the treatment couch dynamic motion. This allows for I setup in the treatment room rather than multiple setups for each treatment position, which would have been previously required. Dose-volume histograms are utilized to evaluate the dose delivered to structures in the beam exit region. This technique will allow for precise localization and delivery of a homogeneous dose to the entire CSF space. PMID:12521071

Chapek, Julie; Watson, Gordon; Smith, Lynn M; Leavitt, Dennis D

2002-01-01

243

An analysis of breast motion using high-frequency, dense surface points captured by an optical sensor during radiotherapy treatment delivery  

NASA Astrophysics Data System (ADS)

Patient motion is an important factor affecting the quality of external beam radiotherapy in breast patients. We analyse the motion of a dense set of surface points on breast patients throughout their treatment schedule to assess the magnitude and stability of motion, in particular, with respect to breast volume. We use an optical sensor to measure the surface motion of 13 breast cancer patients. Patients were divided into two cohorts dependent upon breast volume. Measurements were made during radiotherapy treatment beam delivery for an average of 12 fractions per patient (total 158 datasets). The motion of each surface point is parameterized in terms of its period, amplitude and relative phase. Inter-comparison of the motion parameters across treatment schedules and between patients is made through the creation of corresponding regions on the breast surfaces. The motion period is spatially uniform and is similar in both patient groups (mean 4 s), with the small volume cohort exhibiting greater inter-fraction period variability. The mean motion amplitude is also similar in both groups with a range between 2 mm and 4 mm and an inter-fraction variability generally less than 1 mm. There is a phase lag of up to 0.4 s across the breast, led by the sternum. Breast patient motion is reasonably stable between and during treatment fractions, with the large volume cohort exhibiting greater repeatability than the small volume one.

Price, G. J.; Sharrock, P. J.; Marchant, T. E.; Parkhurst, J. M.; Burton, D.; Jain, P.; Price, P.; Moore, C. J.

2009-11-01

244

Advances in Drug Delivery  

NASA Astrophysics Data System (ADS)

In this article, we review critical aspects in the area of drug delivery. Specifically, delivery of siRNA, remote-controlled delivery, noninvasive delivery, and nanotechnology in drug delivery are reviewed.

Timko, Brian P.; Whitehead, Kathryn; Gao, Weiwei; Kohane, Daniel S.; Farokhzad, Omid; Anderson, Daniel; Langer, Robert

2011-08-01

245

Rotational IMRT delivery using a digital linear accelerator in very high dose rate 'burst mode'.  

PubMed

Recently, there has been a resurgence of interest in arc-based IMRT, through the use of 'conventional' multileaf collimator (MLC) systems that can treat large tumor volumes in a single, or very few pass(es) of the gantry. Here we present a novel 'burst mode' modulated arc delivery approach, wherein 2000 monitor units per minute (MU min(-1)) high dose rate bursts of dose are facilitated by a flattening-filter-free treatment beam on a Siemens Artiste (Oncology Care Systems, Siemens Medical Solutions, Concord, CA, USA) digital linear accelerator in a non-clinical configuration. Burst mode delivery differs from continuous mode delivery, used by Elekta's VMAT (Elekta Ltd, Crawley, UK) and Varian's RapidArc (Varian Medical Systems, Palo Alto, CA, USA) implementations, in that dose is not delivered while MLC leaves are moving. Instead, dose is delivered in bursts over very short arc angles and only after an MLC segment shape has been completely formed and verified by the controller. The new system was confirmed to be capable of delivering a wide array of clinically relevant treatment plans, without machine fault or other delivery anomalies. Dosimetric accuracy of the modulated arc platform, as well as the Prowess (Prowess Inc., Concord, CA, USA) prototype treatment planning version utilized here, was quantified and confirmed, and delivery times were measured as significantly brief, even with large hypofractionated doses. The burst mode modulated arc approach evaluated here appears to represent a capable, accurate and efficient delivery approach. PMID:21364260

Salter, Bill J; Sarkar, Vikren; Wang, Brian; Shukla, Himanshu; Szegedi, Martin; Rassiah-Szegedi, Prema

2011-03-02

246

Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis  

PubMed Central

Background In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model. Methods Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation. Results The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR and ELISA. Human eNOS ELISA levels were significantly raised 24 hours after transfection compared to controls (125 pg eNOS compared to <50 pg for all controls including naked DNA). Local eNOS production suppressed smooth muscle cell proliferation and promoted re-endothelialization of the artery showing a significant reduction in restenosis of 1.75 neointima/media ratio for stents with lipoplexes encoding eNOS compared with 2.3 neointima/media ratio for stents with lipoplexes encosing an empty vector. Conclusions These results support the hypothesis that a potent non-viral gene vector encoding for eNOS coated onto a stent can inhibit restenosis through inhibition of smooth muscle cell growth and promotion of a healthy endothelium.

2010-01-01

247

A magnetic chitosan hydrogel for sustained and prolonged delivery of Bacillus Calmette-Guérin in the treatment of bladder cancer.  

PubMed

The aim of this study was to develop a magnetic thermosensitive hydrogel as intravesical Bacillus Calmette-Guérin (BCG) delivery system, which was formulated with chitosan (CS), ?-glycerophosphate (GP) and Fe3O4 magnetic nanoparticle (Fe3O4-MNP). The gelation time and magnetic response of the gel system were investigated. The morphology of the gel was displayed by scanning electron microscope. Frozen section examination was creatively employed for exhibiting the structure of the gel and determining its intravesical residence time. The antitumor effect and local immune activity of BCG loaded magnetic gel were evaluated. The flowing solution of CS/GP under room temperature could gelate rapidly at body temperature both in vitro and in vivo. The magnetic injectable hydrogels significantly prolonged intravesical BCG residence time under an applied magnetic field. In comparison to traditional BCG therapy for superficial bladder tumor, BCG delivered by the gel system induced a stronger Th1 immune response and revealed higher antitumor efficacy. PMID:24070571

Zhang, Dong; Sun, Peng; Li, Peng; Xue, Aibing; Zhang, Xiaokai; Zhang, Haiyang; Jin, Xunbo

2013-09-24

248

Studies on the development of colon targeted oral drug delivery systems for ornidazole in the treatment of amoebiasis.  

PubMed

The aim of the present study is to develop colon-targeted drug delivery systems for ornidazole using guar gum as a carrier. The core formulation containing ornidazole was directly compressed. Compression-coated tablets of ornidazole containing various proportions of guar gum in the coat were prepared. All the formulations were evaluated for hardness and drug content uniformity and were subjected to in vitro drug release studies. The amount of ornidazole released from tablets at different time intervals was estimated by the HPLC method. The compression-coated formulations released less than 8% of ornidazole in the physiological environment of stomach and small intestine. The compression-coated tablets with 85%, 75%, and 65% of guar gum coat released about 21%, 38%, and 73% of ornidazole, respectively, in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression-coated ornidazole tablets with either 65% (OLV-65) or 75% (OLV-75) of guar gum coat are most likely to provide targeting of ornidazole for local action in the colon owing to its minimal release of the drug in the first 5 hr. The ornidazole compression-coated tablets showed no change in physical appearance, drug content, or in dissolution pattern after storage at 40 degrees C/75% relative humidity for 6 months. PMID:12746057

Krishnaiah, Y S R; Muzib, Y Indira; Rao, G Srinivasa; Bhaskar, P; Satyanarayana, V

249

What is the best treatment for fluctuating Parkinson's disease: continuous drug delivery or deep brain stimulation of the subthalamic nucleus?  

PubMed

Motor complications impair quality of life and cause severe disability in patients with advanced Parkinson's disease (PD). Since they are often refractory to medical therapy, interventional therapies have been developed, which can provide a considerable reduction of daily off-time and dopaminergic dyskinesias. Continuous dopaminergic drug delivery (CDD) is based on the steady stimulation of striatal dopamine receptors by subcutaneous apomorphine or duodenal L: -DOPA infusions via portable minipumps. Advances in the understanding of basal ganglia functioning and in neurosurgical, electrophysiological and neuroimaging techniques have led to a renaissance of neurosurgery for advanced PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most invasive procedure promising great benefit and the highest level of independency for suitable patients, but is definitely associated with surgical risks and DBS-related side effects. Each of these more or less invasive therapy options has its own profile, and a thorough consideration of its advantages and drawbacks for the individual situation is mandatory. In this paper, we summarize relevant facts for this decision and provide some guidelines for a responsible counseling of eligible patients. PMID:21188435

Hilker, Rüdiger; Antonini, Angelo; Odin, Per

2010-12-25

250

Optimal Control of Hepatitis C Antiviral Treatment Programme Delivery for Prevention amongst a Population of Injecting Drug Users  

PubMed Central

In most developed countries, HCV is primarily transmitted by injecting drug users (IDUs). HCV antiviral treatment is effective, and deemed cost-effective for those with no re-infection risk. However, few active IDUs are currently treated. Previous modelling studies have shown antiviral treatment for active IDUs could reduce HCV prevalence, and there is emerging interest in developing targeted IDU treatment programmes. However, the optimal timing and scale-up of treatment is unknown, given the real-world constraints commonly existing for health programmes. We explore how the optimal programme is affected by a variety of policy objectives, budget constraints, and prevalence settings. We develop a model of HCV transmission and treatment amongst active IDUs, determine the optimal treatment programme strategy over 10 years for two baseline chronic HCV prevalence scenarios (30% and 45%), a range of maximum annual budgets (50,000–300,000 per 1,000 IDUs), and a variety of objectives: minimising health service costs and health utility losses; minimising prevalence at 10 years; minimising health service costs and health utility losses with a final time prevalence target; minimising health service costs with a final time prevalence target but neglecting health utility losses. The largest programme allowed for a given budget is the programme which minimises both prevalence at 10 years, and HCV health utility loss and heath service costs, with higher budgets resulting in greater cost-effectiveness (measured by cost per QALY gained compared to no treatment). However, if the objective is to achieve a 20% relative prevalence reduction at 10 years, while minimising both health service costs and losses in health utility, the optimal treatment strategy is an immediate expansion of coverage over 5–8 years, and is less cost-effective. By contrast, if the objective is only to minimise costs to the health service while attaining the 20% prevalence reduction, the programme is deferred until the final years of the decade, and is the least cost-effective of the scenarios.

Vickerman, Peter; Vassall, Anna; Hickman, Matthew

2011-01-01

251

Twin delivery.  

PubMed

The incidence of twin pregnancy has increased worldwide over the past 10 years largely as a consequence of the assisted reproductive technologies. Issues such as intrapartum monitoring and operative interventions, especially with regard to the second twin, provide a unique challenge in labour and delivery. Epidemiological data suggest that the term twin has a threefold higher mortality rate than the singleton. It is the authors' view that many aspects of twin delivery deserve as much import as those features of twin gestations such as pre-term birth and intrauterine growth restriction that, to date, have received much of the research and clinical interest in this area. Indications for elective Caesarean section are presented, incorporating new data derived from the delivery of the term singleton breech, and implications on the timing thereof are discussed. Vaginal delivery of both twins presenting by the vertex is recommended as safe as long as guidelines for the conduct of such delivery are followed. The recommended time interval between twins as well as the use of epidural, fetal monitoring and ultrasound in the delivery room are discussed. The second twin presenting as a non-vertex presents an urgent dilemma for accoucheurs. Data suggest that internal version and breech extractions are safer than external cephalic version provided that the appropriate techniques are applied. It is revealed, however, that the use of elective Caesarean section in this group of babies has not been subject to randomized controlled studies of sufficient power to determine the best method of delivery of the second twin - particularly in the low-birth-weight baby. PMID:11866496

Barrett, J F R; Ritchie, W Knox

2002-02-01

252

Patient navigation for American Indians undergoing cancer treatment: utilization and impact on care delivery in a regional health care center  

PubMed Central

Purpose To assess patient navigation (PN) utilization and its impact on treatment interruptions and clinical trial enrollment among American Indian (AI) cancer patients. Methods Between February 2004 and September 2009, 332 AI cancer patients received PN services throughout cancer treatment. The PN program provided culturally-competent navigators to assist patients with navigating cancer therapy, obtaining medications, insurance issues, communicating with medical providers, and travel and lodging logistics. Data on utilization and trial enrollment were prospectively collected. Data for a historical control group of 70 AI patients who did not receive PN services were used to compare treatment interruptions among those undergoing PN during curative radiation therapy (subgroup of 123 patients). Results The median number of contacts with a navigator was 12 (range, 1-119). The median time spent with the navigator at first contact was 40 minutes (range 10-250 min.) and 15 min for subsequent contacts. Patients treated with radiation therapy with curative intent who underwent PN had fewer days of treatment interruption (mean, 1.7 days; 95% CI, 1.1-2.2 days) than historical controls who did not receive PN services (mean, 4.9 days; 95% CI, 2.9-6.9 days). Of the 332 patients, 72 (22%; 95% CI, 17-26%) were enrolled on a clinical treatment trial or cancer control protocol. Conclusions PN was associated with fewer treatment interruptions and relatively high rates of clinical trial enrollment among AI cancer patients compared to national reports.

Guadagnolo, B. Ashleigh; Boylan, Amy; Sargent, Michelle; Koop, David; Brunette, Deb; Kanekar, Shalini; Shortbull, Vanessa; Molloy, Kevin; Petereit, Daniel G.

2010-01-01

253

Studies on the development of oral colon targeted drug delivery systems for metronidazole in the treatment of amoebiasis.  

PubMed

The aim of the present study is to develop colon targeted drug delivery systems for metronidazole using guar gum as a carrier. Matrix, multilayer and compression coated tablets of metronidazole containing various proportions of guar gum were prepared. All the formulations were evaluated for the hardness, drug content uniformity, and were subjected to in vitro drug release studies. The amount of metronidazole released from tablets at different time intervals was estimated by high performance liquid chromatography method. Matrix tablets and multilayer tablets of metronidazole released 43-52% and 25-44% of the metronidazole, respectively, in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. Both the formulations failed to control the drug release within 5 h of the dissolution study in the physiological environment of stomach and small intestine. The compression coated formulations released less than 1% of metronidazole in the physiological environment of stomach and small intestine. When the dissolution study was continued in simulated colonic fluids, the compression coated tablet with 275 mg of guar gum coat released another 61% of metronidazole after degradation by colonic bacteria at the end of 24 h of the dissolution study. The compression coated tablets with 350 and 435 mg of guar gum coat released about 45 and 20% of metronidazole, respectively, in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that compression coated metronidazole tablets with either 275 or 350 mg of guar gum coat is most likely to provide targeting of metronidazole for local action in the colon owing to its minimal release of the drug in the first 5 h. The metronidazole compression coated tablets showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6 months. PMID:11891069

Krishnaiah, Y S R; Bhaskar Reddy, P R; Satyanarayana, V; Karthikeyan, R S

2002-04-01

254

European guidelines for topical photodynamic therapy part 1: treatment delivery and current indications - actinic keratoses, Bowen's disease, basal cell carcinoma.  

PubMed

Topical photodynamic therapy (PDT) is a widely used non-invasive treatment for certain non-melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High efficacy is demonstrated for PDT using standardized protocols in non-hyperkeratotic actinic keratoses, Bowen's disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain-minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses. PMID:23181594

Morton, C A; Szeimies, R-M; Sidoroff, A; Braathen, L R

2012-11-26

255

Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene  

Microsoft Academic Search

Osteoarthritis in horses and in humans is a significant social and economic problem and continued research and improvements in therapy are needed. Because horses have naturally occurring osteoarthritis, which is similar to that of humans, the horse was chosen as a species with which to investigate gene transfer as a potential therapeutic modality for the clinical treatment of osteoarthritis. Using

DD Frisbie; SC Ghivizzani; PD Robbins; CH Evans; CW McIlwraith

2002-01-01

256

Intra-articular drug delivery systems for the treatment of rheumatic diseases: A review of the factors influencing their performance  

Microsoft Academic Search

Osteoarthritis and rheumatoid arthritis are rheumatic diseases for which a curative treatment does not currently exist. Their management is directed towards pain relief achieved with different classes of drugs among which non-steroidal and steroidal anti-inflammatory substances are the most frequently used agents. Nevertheless, the oral or systemic administration of such drugs is hindered by numerous side effects, which could be

N. Butoescu; O. Jordan; E. Doelker

2009-01-01

257

Efficacy of a Combined Intracerebral and Systemic Gene Delivery Approach for the Treatment of a Severe Lysosomal Storage Disorder  

PubMed Central

Multiple sulfatase deficiency (MSD), a severe autosomal recessive disease is caused by mutations in the sulfatase modifying factor 1 gene (Sumf1). We have previously shown that in the Sumf1 knockout mouse model (Sumf1?/?) sulfatase activities are completely absent and, similarly to MSD patients, this mouse model displays growth retardation and early mortality. The severity of the phenotype makes MSD unsuitable to be treated by enzyme replacement or bone marrow transplantation, hence the importance of testing the efficacy of novel treatment strategies. Here we show that recombinant adeno-associated virus serotype 9 (rAAV9) vector injected into the cerebral ventricles of neonatal mice resulted in efficient and widespread transduction of the brain parenchyma. In addition, we compared a combined, intracerebral ventricles and systemic, administration of an rAAV9 vector encoding SUMF1 gene to the single administrations—either directly in brain, or systemic alone —in MSD mice. The combined treatment resulted in the global activation of sulfatases, near-complete clearance of glycosaminoglycans (GAGs) and decrease of inflammation in both the central nervous system (CNS) and visceral organs. Furthermore, behavioral abilities were improved by the combined treatment. These results underscore that the “combined” mode of rAAV9 vector administration is an efficient option for the treatment of severe whole-body disorders.

Spampanato, Carmine; De Leonibus, Elvira; Dama, Paola; Gargiulo, Annagiusi; Fraldi, Alessandro; Sorrentino, Nicolina Cristina; Russo, Fabio; Nusco, Edoardo; Auricchio, Alberto; Surace, Enrico M; Ballabio, Andrea

2011-01-01

258

Uniformity of Evidence-Based Treatments in Practice? Therapist Effects in the Delivery of Cognitive Processing Therapy for PTSD  

ERIC Educational Resources Information Center

|Objective: Various factors contribute to the effective implementation of evidence-based treatments (EBTs). In this study, cognitive processing therapy (CPT) was administered in a Veterans Affairs (VA) posttraumatic stress disorder (PTSD) specialty clinic in which training and supervision were provided following VA implementation guidelines. The…

Laska, Kevin M.; Smith, Tracey L.; Wislocki, Andrew P.; Minami, Takuya; Wampold, Bruce E.

2013-01-01

259

Immune activation and target organ damage are consequences of hydrodynamic treatment but not delivery of naked siRNAs in mice.  

PubMed

Short-interfering RNAs (siRNAs), key mediators of RNA interference comprise a promising therapeutic tool, although side effects such as interferon (IFN) response are still not perfectly understood. Further, delivery to target organs is a major challenge, possibly associated with side effects including immune activation or organ damage. We investigated whether immune activation as a consequence of double-stranded RNA induced IFN response (Jak/STAT pathway activation or cytokine production) or target organ damage is induced by in vivo low-volume (LV) or high-volume (HV) hydrodynamic delivery or treatment with naked siRNA. NMRI mice were injected with naked siRNAs or saline by hydrodynamic injection (HDI) and positive control mice received polyinosinic-polycytidilic acid (poly I:C). LV (1?mL/mouse) and HV (10% of body weight) HDI were compared. After LV HDI, STAT1 and OAS1 gene expression inflammatory cytokine plasma levels and target organ injury were assessed. LV HDI induced slight alanine aminotransferase elevation and mild hepatocyte injury, whereas HV HDI resulted in high ALAT level and extensive hepatocyte necrosis. STAT1 or OAS1 was not induced by LV siRNA; however, HV saline led to a time-dependent slight increase in gene expression. Inflammatory cytokine plasma level and organ histology and functional parameters demonstrated no damage following LV HDI with or without siRNA. Our data demonstrate that naked siRNAs may be harnessed, without the induction of IFN response or immune activation, and that LV HDI is preferable, because HV HDI may cause organ damage. PMID:21749298

Rácz, Zsuzsanna; Godó, Mária; Révész, Csaba; Hamar, Péter

2011-06-01

260

Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy: a 12-month follow-up study  

PubMed Central

Background The therapeutic effects of Meriva®, a curcumin-phospholipid (lecithin) delivery system (formulated as Norflo® tablets), on visual acuity and retinal thickness in patients with acute and chronic central serous chorioretinopathy was previously investigated in a six-month open-label study. Methods In this follow-up study, visual acuity was again assessed by ophthalmologic evaluation and retinal thickness by optical coherence tomography (OCT). Norflo tablets were administered twice daily to patients with central serous chorioretinopathy. The study group consisted of 12 patients (total 18 eyes) who completed 12 months of follow-up. The primary endpoint was change in visual acuity before and after treatment with Norflo, and change in neuroretinal or retinal pigment epithelium detachment on OCT was the secondary endpoint. Results After 12 months of therapy, no eyes showed further reduction in visual acuity, 39% showed stabilization, and 61% showed statistically significant improvement (P = 0.0001 by Student’s t-test and P = 0.0005 by Wilcoxon signed rank test). Ninety-five percent of eyes showed a reduction in neuroretinal or retinal pigment epithelium detachment and 5% showed stabilization. The difference in retinal thickness after 12 months was statistically significant (P = 0.0001 by Student’s t-test and P = 0.0004 by Wilcoxon signed rank test). Conclusion These results, albeit preliminary, confirm our previous finding that this curcumin delivery system is effective in the management of central serous chorioretinopathy. When administered in a bioavailable formulation, curcumin is worth considering as a therapeutic agent for the management of inflammatory and degenerative eye conditions involving activation of retinal microglial cells.

Mazzolani, Fabio; Togni, Stefano

2013-01-01

261

Targeted co-delivery of docetaxel, cisplatin and herceptin by vitamin E TPGS-cisplatin prodrug nanoparticles for multimodality treatment of cancer.  

PubMed

We developed a nanocarrier system of herceptin-conjugated nanoparticles of d-alpha-tocopheryl-co-poly(ethylene glycol) 1000 succinate (TPGS)-cisplatin prodrug (HTCP NPs) for targeted co-delivery of cisplatin, docetaxel and herceptin for multimodality treatment of breast cancer of high human epidermal growth factor receptor 2 (HER2) overexpression. Co-polymers poly(lactic acid)-TPGS (PLA-TPGS) and carboxyl group-terminated TPGS (TPGS-COOH) were also added in the polymeric matrix to stabilize the prodrug nanoparticles and to facilitate herceptin conjugation. The HTCP NPs of high, moderate and low docetaxel versus cisplatin ratio were prepared by the nanoprecipitation method, which showed a pH-sensitive release for both anticancer drugs. The therapeutic effects of HTCP NPs were evaluated in vitro and compared with Taxotere® and cisplatin. The HTCP NPs of high docetaxel versus cisplatin ratio were found to have better efficacy than those of moderate and low docetaxel versus cisplatin ratio. The targeting effects of the HTCP NPs were demonstrated by a much lower IC50 value of 0.0201+0.00780+0.1629?g/mL of docetaxel+cisplatin+herceptin for SK-BR-3 cells, which are of high HER2 overexpression, than that of 0.225+0.0875+1.827?g/mL for NIH3T3 cells, which are of low HER2 overexpression, after 24h incubation. The same design of TPGS prodrug nanoparticles can also be applied for targeted co-delivery of other hydrophilic and hydrophobic drugs. PMID:23403395

Mi, Yu; Zhao, Jing; Feng, Si-Shen

2013-02-10

262

Accurate Computation of Ballistic Trajectory Using Least Square Approximation with Crout's Method  

Microsoft Academic Search

Ballistic Trajectory Computation Program is a part of weapon delivery system and it is responsible for accurate delivery of the weapon. Mach number (M) and Coefficient of drag (Cd) are critical parameters in external Ballistic computation and are used in computation of Impact Point. Cd Vs M relation is not available in a functional form. These data are available in

V. Verma; B. Somani

2009-01-01

263

Focused ultrasound induced blood-brain barrier disruption to enhance chemotherapeutic drugs (BCNU) delivery for glioblastoma treatment  

Microsoft Academic Search

Focused ultrasound has been recently found to capable of temporally and reversibly disrupt local blood-brain barrier (BBB) and opens new frontier in delivering varies type of drugs into brain for central nerve system (CNS) disorder treatment. In this study, we aim to investigate the feasibility of delivering 1, 3-bits (2-chloroethyl) -1-nitrosourea (BCNU) to treat glioblastoma in animal models and evaluate

Hao-Li Liu; Mu-Yi Hua; Pin-Yuan Chen; Chiung-Yin Huang; Jiun-Jie Wang; Kuo-Chen Wei

2010-01-01

264

Benchmarking treatment of schizophrenia: a comparison of service delivery by the national government and by state and local providers.  

PubMed

This study compared treatment of schizophrenia in two types of organization: a national, government-operated health care system, the Department of Veterans Affairs (VA), and in hospitals and clinics operated by state and local providers. Between 1994 and 1996, 746 male patients with a clinical diagnosis of schizophrenia residing in two states in the Southeast and Midwest were surveyed: 192 VA inpatients were compared with 96 non-VA inpatients, and 274 VA outpatients were compared with 184 non-VA outpatients. VA patients were older and had higher incomes than non-VA patients but did not differ significantly on measures of clinical status, satisfaction with providers, or community adjustment. VA outpatients were more likely to have been hospitalized during the previous year than non-VA outpatients and were less likely to have received services from a day hospital, from a case manager or social worker, or to have received crisis intervention services. On 5 of 26 Schizophrenic Patient Outcomes Research Team treatment recommendations, a smaller proportion of VA than non-VA patients adhered to standards. Four of these reflected reduced access among VA patients to psychosocial services such as work therapy, job training, or case management services. Cross-sectional surveys can be used to compare quality of care across service systems. VA care was associated with similar satisfaction and clinical outcomes but greater reliance on hospital treatment and less use of community-based psychosocial services. PMID:10789997

Rosenheck, R A; Desai, R; Steinwachs, D; Lehman, A

2000-04-01

265

Efficacy of Intracerebral Delivery of Carboplatin in Combination With Photon Irradiation for Treatment of F98 Glioma-Bearing Rats  

SciTech Connect

Purpose: To evaluate the efficacy of prolonged intracerebral (i.c.) administration of carboplatin by means of ALZET osmotic pumps, in combination with radiotherapy for the treatment of intracranial F98 glioma in rats. Methods and Materials: Seven days after stereotactic implantation of F98 glioma cells into the brains of Fischer rats, carboplatin was administrated i.c. by means of ALZET pumps over 6 days. Rats were treated at the European Synchrotron Radiation Facility with a single 15-Gy X-ray dose, either given alone or 24 h after administration of carboplatin. Results: Untreated rats had a mean survival time (MST) {+-} SE of 23 {+-} 1 days, compared with 44 {+-} 3 days for X-irradiated animals and 69 {+-} 20 days for rats that received carboplatin alone, with 3 of 13 of these surviving >195 days. Rats that received carboplatin followed by X-irradiation had a MST of >142 {+-} 21 days and a median survival time of >195 days, with 6 of 11 rats (55%) still alive at the end of the study. The corresponding percentage increases in lifespan, based on median survival times, were 25%, 85%, and 713%, respectively, for carboplatin alone, radiotherapy alone, or the combination. Conclusions: Our data demonstrate that i.c. infusion of carboplatin by means of ALZET pumps in combination with X-irradiation is highly effective for the treatment of the F98 glioma. They provide strong support for the approach of concomitantly administering chemo- and radiotherapy for the treatment of brain tumors.

Rousseau, Julia [Institut National de la Sante et de la Recherche Medicale U836, Equipe 6, Grenoble (France); Universite Joseph Fourier, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Barth, Rolf F.; Moeschberger, Melvin L. [Department of Pathology and Division of Biostatistics, Ohio State University, Columbus, OH (United States); Elleaume, Helene [Institut National de la Sante et de la Recherche Medicale U836, Equipe 6, Grenoble (France); Universite Joseph Fourier, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Centre Hospitalier Universitaire, Grenoble (France)], E-mail: h.elleaume@esrf.fr

2009-02-01

266

The effectiveness of community-based delivery of an evidence-based treatment for adolescent substance use  

PubMed Central

This study evaluates the effectiveness of Motivational Enhancement Therapy/Cognitive Behavioral Therapy-5 (MET/CBT-5) when delivered in community practice settings relative to standard community-based adolescent treatment. A quasi-experimental strategy was used to adjust for pre-treatment differences between the MET/CBT-5 sample (n = 2293) and those who received standard care (n = 458). Results suggest that youth who received MET/CBT-5 fared better than comparable youth in the control group on five out of six 12-month outcomes. A low follow-up rate (54%) in the MET/CBT-5 sample raised concerns about nonresponse bias in the treatment effect estimates. Sensitivity analyses suggest that while modest differences in outcomes between the MET/CBT-5 nonrespondents and respondents would yield no significant differences between the two groups on two of the six outcomes, very large differences in outcomes between responders and nonresponders would be required for youth receiving MET/CBT-5 to have fared better had they received standard outpatient care.

Hunter, Sarah B.; Ramchand, Rajeev; Griffin, Beth Ann; Suttorp, Marika J; McCaffrey, Daniel; Morral, Andrew

2011-01-01

267

Delivery parameter variations and early clinical outcomes of volumetric modulated arc therapy for 31 prostate cancer patients: an intercomparison of three treatment planning systems.  

PubMed

We created volumetric modulated arc therapy (VMAT) plans for 31 prostate cancer patients using one of three treatment planning systems (TPSs)--ERGO++, Monaco, or Pinnacle--and then treated those patients. A dose of 74 Gy was prescribed to the planning target volume (PTV). The rectum, bladder, and femur were chosen as organs at risk (OARs) with specified dose-volume constraints. Dose volume histograms (DVHs), the mean dose rate, the beam-on time, and early treatment outcomes were evaluated and compared. The DVHs calculated for the three TPSs were comparable. The mean dose rates and beam-on times for Ergo++, Monaco, and SmartArc were, respectively, 174.3?±?17.7, 149.7?±?8.4, and 185.8?±?15.6?MU/min and 132.7?±?8.4, 217.6?±?13.1, and 127.5?±?27.1?sec. During a follow-up period of 486.2?±?289.9 days, local recurrence was not observed, but distant metastasis was observed in a single patient. Adverse events of grade 3 to grade 4 were not observed. The mean dose rate for Monaco was significantly lower than that for ERGO++ and SmartArc (P < 0.0001), and the beam-on time for Monaco was significantly longer than that for ERGO++ and SmartArc (P < 0.0001). Each TPS was successfully used for prostate VMAT planning without significant differences in early clinical outcomes despite significant TPS-specific delivery parameter variations. PMID:23401667

Tsutsumi, Shinichi; Hosono, Masako N; Tatsumi, Daisaku; Miki, Yoshitaka; Masuoka, Yutaka; Ogino, Ryo; Ishii, Kentaro; Shimatani, Yasuhiko; Miki, Yukio

2013-01-15

268

Ethosomes® and transfersomes® containing linoleic acid: physicochemical and technological features of topical drug delivery carriers for the potential treatment of melasma disorders.  

PubMed

Two vesicular colloidal carriers, ethosomes® and transfersomes® were proposed for the topical delivery of linoleic acid, an active compound used in the therapeutic treatment of hyperpigmentation disorders, i.e. melasma, which is characterized by an increase of the melanin production in the epidermis. Dynamic light scattering was used for the physicochemical characterization of vesicles and mean size, size distribution and zeta potential were evaluated. The stability of formulations was also evaluated using the Turbiscan Lab® Expert based on the analysis of sample transmittance and photon backscattering. Ethosomes® and transfersomes® were prepared using Phospholipon 100 G®, as the lecithin component, and ethanol and sodium cholate, as edge activator agents, respectively. Linoleic acid at 0.05% and 0.1% (w/v) was used as the active ingredient and entrapped in colloidal vesicles. Technological parameters, i.e. entrapment efficacy, drug release and permeation profiles, were also investigated. Experimental findings showed that physicochemical and technological features of ethosomes® and transfersomes® were influenced by the lipid composition of the carriers. The percutaneous permeation experiments of linoleic acid-loaded ethosomes® and transfersomes® through human stratum corneum-epidermidis membranes showed that both carriers are accumulated in the skin membrane model as a function of their lipid compositions. The findings reported in this investigation showed that both vesicular carriers could represent a potential system for the topical treatment of hyperpigmentation disorders. PMID:21960035

Celia, Christian; Cilurzo, Felisa; Trapasso, Elena; Cosco, Donato; Fresta, Massimo; Paolino, Donatella

2012-02-01

269

Signaling, Delivery and Age as Emerging Issues in the Benefit/Risk Ratio Outcome of tPA For Treatment of CNS Ischemic Disorders  

PubMed Central

Stroke is a leading cause of morbidity and mortality. While tissue-type plasminogen activator (tPA) remains the only FDA approved treatment for ischemic stroke, clinical use of tPA has been constrained to roughly 3% of eligible patients because of the danger of intracranial hemorrhage and a narrow 3h time window for safe administration. Basic science studies indicate that tPA enhances excitotoxic neuronal cell death. In this review, the beneficial and deleterious effects of tPA in ischemic brain are discussed along with emphasis on development of new approaches towards treatment of patients with acute ischemic stroke. In particular, roles of tPA induced signaling and a novel delivery system for tPA administration based on tPA coupling to carrier red blood cells will be considered as therapeutic modalities for increasing tPA benefit/risk ratio. The concept of the neurovascular unit will be discussed in the context of dynamic relationships between tPA-induced changes in cerebral hemodynamics and histopathologic outcome of CNS ischemia. Additionally, the role of age will be considered since thrombolytic therapy is being increasingly used in the pediatric population, but there are few basic science studies of CNS injury in pediatric animals.

Armstead, William M; Ganguly, Kumkum; Kiessling, JW; Riley, John; Chen, Xiao-Han; Smith, Douglas H; Stein, Sherman C.; Higazi, Abd AR; Cines, Douglas B; Bdeir, Khalil; Zaitsev, Sergei; Muzykantov, Vladimir R.

2010-01-01

270

Signaling, delivery and age as emerging issues in the benefit/risk ratio outcome of tPA For treatment of CNS ischemic disorders.  

PubMed

Stroke is a leading cause of morbidity and mortality. While tissue-type plasminogen activator (tPA) remains the only FDA-approved treatment for ischemic stroke, clinical use of tPA has been constrained to roughly 3% of eligible patients because of the danger of intracranial hemorrhage and a narrow 3 h time window for safe administration. Basic science studies indicate that tPA enhances excitotoxic neuronal cell death. In this review, the beneficial and deleterious effects of tPA in ischemic brain are discussed along with emphasis on development of new approaches toward treatment of patients with acute ischemic stroke. In particular, roles of tPA-induced signaling and a novel delivery system for tPA administration based on tPA coupling to carrier red blood cells will be considered as therapeutic modalities for increasing tPA benefit/risk ratio. The concept of the neurovascular unit will be discussed in the context of dynamic relationships between tPA-induced changes in cerebral hemodynamics and histopathologic outcome of CNS ischemia. Additionally, the role of age will be considered since thrombolytic therapy is being increasingly used in the pediatric population, but there are few basic science studies of CNS injury in pediatric animals. PMID:20405577

Armstead, William M; Ganguly, Kumkum; Kiessling, J W; Riley, John; Chen, Xiao-Han; Smith, Douglas H; Stein, Sherman C; Higazi, Abd A R; Cines, Douglas B; Bdeir, Khalil; Zaitsev, Sergei; Muzykantov, Vladimir R

2010-04-01

271

Delivery Parameter Variations and Early Clinical Outcomes of Volumetric Modulated Arc Therapy for 31 Prostate Cancer Patients: An Intercomparison of Three Treatment Planning Systems  

PubMed Central

We created volumetric modulated arc therapy (VMAT) plans for 31 prostate cancer patients using one of three treatment planning systems (TPSs)—ERGO++, Monaco, or Pinnacle—and then treated those patients. A dose of 74 Gy was prescribed to the planning target volume (PTV). The rectum, bladder, and femur were chosen as organs at risk (OARs) with specified dose-volume constraints. Dose volume histograms (DVHs), the mean dose rate, the beam-on time, and early treatment outcomes were evaluated and compared. The DVHs calculated for the three TPSs were comparable. The mean dose rates and beam-on times for Ergo++, Monaco, and SmartArc were, respectively, 174.3?±?17.7, 149.7?±?8.4, and 185.8?±?15.6?MU/min and 132.7?±?8.4, 217.6?±?13.1, and 127.5?±?27.1?sec. During a follow-up period of 486.2?±?289.9 days, local recurrence was not observed, but distant metastasis was observed in a single patient. Adverse events of grade 3 to grade 4 were not observed. The mean dose rate for Monaco was significantly lower than that for ERGO++ and SmartArc (P < 0.0001), and the beam-on time for Monaco was significantly longer than that for ERGO++ and SmartArc (P < 0.0001). Each TPS was successfully used for prostate VMAT planning without significant differences in early clinical outcomes despite significant TPS-specific delivery parameter variations.

Tsutsumi, Shinichi; Hosono, Masako N.; Tatsumi, Daisaku; Miki, Yoshitaka; Masuoka, Yutaka; Ogino, Ryo; Ishii, Kentaro; Shimatani, Yasuhiko; Miki, Yukio

2013-01-01

272

Breech delivery  

Microsoft Academic Search

Fetuses that present by the breech are at increased risk of trauma and hypoxia during delivery. The threshold for Caesarean section for breech presentation had been low for several years. The result of the term breech trial confirms that planned Caesarean section is the best method of delivering the singleton frank or complete breech at term. The best mode of

Sambit Mukhopadhyay; Sabaratnam Arulkumaran

2002-01-01

273

Twin delivery  

Microsoft Academic Search

The incidence of twin pregnancy has increased worldwide over the past 10 years largely as a consequence of the assisted reproductive technologies. Issues such as intrapartum monitoring and operative interventions, especially with regard to the second twin, provide a unique challenge in labour and delivery. Epidemiological data suggest that the term twin has a threefold higher mortality rate than the

J. F. R. Barrett; W. Knox Ritchie

2002-01-01

274

The effectiveness of community-based delivery of an evidence-based treatment for adolescent substance use.  

PubMed

This study evaluates the effectiveness of motivational enhancement therapy/cognitive behavioral therapy-5 (MET/CBT-5) when delivered in community practice settings relative to standard community-based adolescent treatment. A quasi-experimental strategy was used to adjust for pretreatment differences between the MET/CBT-5 sample (n = 2,293) and those who received standard care (n = 458). Results suggest that youth who received MET/CBT-5 fared better than comparable youth in the control group on five of six 12-month outcomes. A low follow-up rate (54%) in the MET/CBT-5 sample raised concerns about nonresponse bias in the treatment effect estimates. Sensitivity analyses suggest that although modest differences in outcomes between the MET/CBT-5 nonrespondents and respondents would yield no significant differences between the two groups on two of the six outcomes, very large differences in outcomes between responders and nonresponders would be required for youth receiving MET/CBT-5 to have fared better had they received standard outpatient care. PMID:22209657

Hunter, Sarah B; Ramchand, Rajeev; Griffin, Beth Ann; Suttorp, Marika J; McCaffrey, Daniel; Morral, Andrew

2011-12-29

275

Novel Delivery Strategies for Glioblastoma  

PubMed Central

Brain tumors—particularly glioblastoma multiforme (GBM)—pose an important public health problem in the US. Despite surgical and medical advances, the prognosis for patients with malignant gliomas remains grim: current therapy for is insufficient with nearly universal recurrence. A major reason for this failure is the difficulty of delivering therapeutic agents to the brain: better delivery approaches are needed to improve treatment. In this article, we summarize recent progress in drug delivery to the brain, with an emphasis on convection-enhanced delivery of nanocarriers. We examine the potential of new delivery methods to permit novel drug- and gene-based therapies that target brain cancer stem cells (BCSCs) and discuss the use of nanomaterials for imaging of tumors and drug delivery.

Zhou, Jiangbing; Atsina, Kofi-Buaku; Himes, Benjamin T.; Strohbehn, Garth W.; Saltzman, W. Mark

2012-01-01

276

Using In-Service and Coaching to Increase Teachers' Accurate Use of Research-Based Strategies  

ERIC Educational Resources Information Center

Increasing the accurate use of research-based practices in classrooms is a critical issue. Professional development is one of the most practical ways to provide practicing teachers with training related to research-based practices. This study examined the effects of in-service plus follow-up coaching on first grade teachers' accurate delivery of…

Kretlow, Allison G.; Cooke, Nancy L.; Wood, Charles L.

2012-01-01

277

Multiparticulate Formulation .. Approach to Colon Specific Drug Delivery: Current Perspectives  

Microsoft Academic Search

Colon specific drug delivery has gained increased importance not just for the delivery of drugs for the treatment of local diseases associated with the colon but also as potential site for the systemic delivery of therapeutic peptide and proteins. To achieve successful colon targeted drug delivery, a drug needs to be protected from degradation, release and\\/or absorption in the upper

Laila Fatima; Ali Asghar; Sajeev Chandran

278

Drug delivery to the ear.  

PubMed

Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Ménière's disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966-2012), Embase (1988-2012), the Cochrane Library and Ovid (1966-2012), using search terms 'drug delivery', 'middle ear', 'inner ear' and 'transtympanic'. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions. PMID:23323784

Hoskison, E; Daniel, M; Al-Zahid, S; Shakesheff, K M; Bayston, R; Birchall, J P

2013-01-01

279

In vivo delivery of human acid ceramidase via cord blood transplantation and direct injection of lentivirus as novel treatment approaches for Farber disease  

PubMed Central

Farber disease is a rare lysosomal storage disorder (LSD) caused by a deficiency of acid ceramidase (AC) activity and subsequent accumulation of ceramide. Currently, there is no treatment for Farber disease beyond palliative care and most patients succumb to the disorder at a very young age. Previously, our group showed that gene therapy using oncoretroviral vectors (RV) could restore enzyme activity in Farber patient cells. The studies described here employ novel RV and lentiviral (LV) vectors that engineer co-expression of AC and a cell surface marking transgene product, human CD25 (huCD25). Transduction of Farber patient fibroblasts and B cells with these vectors resulted in overexpression of AC and led to a 90% and 50% reduction in the accumulation of ceramide, respectively. Vectors were also evaluated in human hematopoietic stem/progenitor cells (HSPCs) and by direct in vivo delivery in mouse models. In a xenotransplantation model using NOD/SCID mice, we found that transduced CD34+ cells could repopulate irradiated recipient animals, as measured by CD25 expression. When virus was injected intravenously into mice, soluble CD25 was detected in the plasma and increased AC activity was present in the liver up to 14 weeks post-injection. These findings suggest that vector and transgene expression can persist long-term and offer the potential of a lasting cure. To our knowledge, this is the first report of in vivo testing of direct gene therapy strategies for Farber disease.

Ramsubir, Shobha; Nonaka, Takahiro; Girbes, Carmen Bedia; Carpentier, Stephane; Levade, Thierry; Medin, Jeffrey A.

2008-01-01

280

Intracerebral delivery of Carboplatin in combination with either 6 MV Photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma  

PubMed Central

Background The purpose of the present study was to compare side-by-side the therapeutic efficacy of a 6-day infusion of carboplatin, followed by X-irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K-edge of Pt, for treatment of F98 glioma bearing rats. Methods Carboplatin was administered intracerebrally (i.c.) to F98 glioma bearing rats over 6?days using AlzetTM osmotic pumps starting 7?days after tumor implantation. Radiotherapy was delivered in a single 15?Gy fraction on day 14 using a conventional 6 MV linear accelerator (LINAC) or 78.8?keV synchrotron X-rays. Results Untreated control animals had a median survival time (MeST) of 33?days. Animals that received either carboplatin alone or irradiation alone with either 78.8?keV or 6 MV had a MeSTs 38 and 33?days, respectively. Animals that received carboplatin in combination with X-irradiation had a MeST of?>?180?days with a 55% cure rate, irrespective of whether they were irradiated with either 78.8 KeV synchrotron X-rays or 6MV photons. Conclusions These studies have conclusively demonstrated the equivalency of i.c. delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays.

2012-01-01

281

GENE DELIVERY TO BONE  

PubMed Central

Gene delivery to bone is useful both as an experimental tool and as a potential therapeutic strategy. Among its advantages over protein delivery are the potential for directed, sustained and regulated expression of authentically processed, nascent proteins. Although no clinical trials have been initiated, there is a substantial pre-clinical literature documenting the successful transfer of genes to bone, and their intraosseous expression. Recombinant vectors derived from adenovirus, retrovirus and lentivirus, as well as non-viral vectors, have been used for this purpose. Both ex vivo and in vivo strategies, including gene-activated matrices, have been explored. Ex vivo delivery has often employed mesenchymal stem cells (MSCs), partly because of their ability to differentiate into osteoblasts. MSCs also have the potential to home to bone after systemic administration, which could serve as a useful way to deliver transgenes in a disseminated fashion for the treatment of diseases affecting the whole skeleton, such as osteoporosis or osteogenesis imperfecta. Local delivery of osteogenic transgenes, particularly those encoding bone morphogenetic proteins, has shown great promise in a number of applications where it is necessary to regenerate bone. These include healing large segmental defects in long bones and the cranium, as well as spinal fusion and treating avascular necrosis.

Evans, C. H.

2012-01-01

282

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study  

PubMed Central

Background Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS?+?SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS?+?SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p?treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

2012-01-01

283

Malaria risk factors in women on intermittent preventive treatment at delivery and their effects on pregnancy outcome in sanaga-maritime, cameroon.  

PubMed

Malaria is known to have a negative impact on pregnant women and their foetuses. The efficacy of Sulfadoxine-Pyrimethamine (SP) used for intermittent preventive treatment (IPT) is being threatened by increasing levels of resistance. This study assessed malaria risk factors in women on intermittent preventive treatment with SP (IPTp-SP) at delivery and their effects on pregnancy outcome in Sanaga-Maritime Division, Cameroon. Socio-economic and obstetrical data of mothers and neonate birth weights were documented. Peripheral blood from 201 mothers and newborns as well as placental and cord blood were used to prepare thick and thin blood films. Maternal haemoglobin concentration was measured. The overall malaria parasite prevalence was 22.9% and 6.0% in mothers and newborns respectively. Monthly income lower than 28000 FCFA and young age were significantly associated with higher prevalence of placental malaria infection (p?=?0.0048 and p?=?0.019 respectively). Maternal infection significantly increased the risk of infection in newborns (OR?=?48.4; p<0.0001). Haemoglobin concentration and birth weight were lower in infected mothers, although not significant. HIV infection was recorded in 6.0% of mothers and increased by 5-folds the risk of malaria parasite infection (OR?=?5.38, p?=?0.007). Attendance at antenatal clinic and level of education significantly influenced the utilisation of IPTp-SP (p<0.0001 and p?=?0.018 respectively). Use of SP and mosquito net resulted in improved pregnancy outcome especially in primiparous, though the difference was not significant. Malaria infection in pregnancy is common and increases the risk of neonatal malaria infection. Preventive strategies are poorly implemented and their utilization has overall reasonable effect on malaria infection and pregnancy outcome. PMID:23762446

Tonga, Calvin; Kimbi, Helen Kuokuo; Anchang-Kimbi, Judith Kuoh; Nyabeyeu, Hervé Nyabeyeu; Bissemou, Zacharie Bissemou; Lehman, Léopold G

2013-06-06

284

More accurate time from the Heathkit most accurate clock  

Microsoft Academic Search

The addition of an auxiliary circuit to the Heathkit GC-1000 clock is described. The circuit, which consists of two integrated circuits, two resistors, and three capacitors, will supply a more accurate timing pulse to the computer. The circuit contains two input signals and produces one output; the inputs are multiplexed seven-digit displays (two digits for hour, minute, and second, and

M. V. Tollefson; R. H. Bloomer Jr.

1986-01-01

285

Drug delivery from jet nebulisers  

Microsoft Academic Search

Maximising the rate of drug delivered in particles small enough to reach the lower respiratory tract from jet nebulisers may allow treatment times to be reduced and thus improve the acceptability of this form of treatment, particularly in very young patients. The role of various technical factors such as driving gas flow (DGF) in determining the rate of drug delivery

M L Everard; A R Clark; A D Milner

1992-01-01

286

Accurate measurements in volume data  

Microsoft Academic Search

An algorithm for very accurate visualization of an iso- surface in a 3D medical dataset has been developed in the past few years. This technique is extended in this paper to several kinds of measurements in which exact geometric information of a selected iso-surface is used to derive volume, length, curvature, connectivity and similar geometric information from an object of

Javier Olivan; Marco K. Bosma; Jaap Smit; S. K. Mun

2001-01-01

287

Method of accurizing rail guns  

Microsoft Academic Search

In space, projectiles with hypervelocity can deliver large amounts of energy to the target. Long range and high accuracy are essential. This report presents a method of improving the accuracy of hypervelocity vehicles by measuring the output velocity and correcting the direction by impulse from a laser beam normal to the projectile flight path. The accurizer is described, trajectory-correction calculations

Farnum

1984-01-01

288

Accurate, inexpensive, thermal expansion microtranslator  

Microsoft Academic Search

We have developed an accurate, inexpensive translator utilizing the thermal expansion of an electrically heated wire. The resistance of the wire, measured in a Wheatstone bridge, provides a readout of the length of the wire based on its temperature coefficient of resistance.

James J. Snyder

1993-01-01

289

Quantification of Horseradish Peroxidase Delivery into the Arterial Wall In Vivo as a Model of Local Drug Treatment: Comparison Between a Porous and a Gel-Coated Balloon Catheter  

SciTech Connect

Purpose: To quantify horseradish peroxidase (HRP) delivery into the arterial wall, as a model of local drug delivery, and to compare two different percutaneous delivery balloons. Methods: Perforated and hydrophilic hydrogel-coated balloon catheters were used to deliver HRP in aqueous solution into the wall of porcine iliac arteries in vivo. HRP solutions of 1 mg/ml were used together with both perforated and hydrophilic hydrogel-coated balloon catheters and 40 mg/ml HRP solutions were used with the hydrogel-coated balloon only. The amount of HRP deposited in the arterial wall was then determined photospectrometrically. Results: Using the 1 mg/ml HRP solution, the hydrogel-coated balloon absorbed 0.047 mg HRP into the coating. Treatment with this balloon resulted in a mean vessel wall concentration of 7.4 {mu}g HRP/g tissue {+-} 93% (standard deviation) (n 7). Treatment with the hydrogel-coated balloon that had absorbed 1.88 mg HRP into the coating (using the 40 mg/ml HRP solution) led to a mean vessel wall concentration of 69.5 {mu}g HRP/g tissue {+-} 74% (n = 7). Treatment with the perforated balloon using 1 mg/ml aqueous HRP solution led to a mean vessel wall concentration of 174 {mu}g/g {+-} 81% (n = 7). Differences between the hydrogel-coated and perforated balloons (1 mg/g solutions of HRP) and between hydrogel-coated balloons (0.047 mg vs 1.88 mg absorbed into the balloon coating) were significant (p < 0.05; two-sided Wilcoxon test). Conclusions: The use of a perforated balloon catheter allowed the delivery of a higher total amount of HRP compared with the hydrogel-coated balloon, but at the cost of a higher systemic HRP application. To deliver 174 {mu}g HRP per gram of vessel wall with the perforated balloon, 6.5 {+-} 1.5 mg HRP were lost into the arterial blood (delivery efficiency range = 0.2%-0.3%). With 0.047 mg HRP loaded into the coating of the hydrogel balloon, 7.4 {mu}g HRP could be applied to 1 g of vessel wall (delivery efficiency 1.7%), and with 1.88 mg HRP loaded into the coating of the hydrogel balloon, 69.5 {mu}g HRP could be applied per gram of vessel wall (delivery efficiency 0.6%)

Dick, Armin; Kromen, Wolfgang [Department of Diagnostic Radiology, University of Technology Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Juengling, Eberhard [Department of Physiology, University of Technology Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Grosskortenhaus, Stephanie [Department of Diagnostic Radiology, University of Technology Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Kammermeier, Helmut [Department of Physiology, University of Technology Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany); Vorwerk, Dierk; Guenther, Rolf W. [Department of Diagnostic Radiology, University of Technology Aachen, Pauwelsstrasse 30, D-52057 Aachen (Germany)

1999-09-15

290

Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. I. Preparation and drug release.  

PubMed

Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug-loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes, and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the CAP phase, decreasing from monocalcium phosphate to monetite to amorphous CAP and calcium pyrophosphate to hydroxyapatite. The sustained release of the two model drugs was shown to be directly relatable to the degradation rate of CAP carriers. It was demonstrated that the degradation rate of the carrier and the drug release kinetics could be made tunable within the time scale of 1-2 h for the most soluble CAP phase, monocalcium phosphate, to 1-2 years for the least soluble one, hydroxyapatite. From the standpoint of antibiotic therapy for osteomyelitis, typically lasting for 6 weeks, the most prospective CAP powder was amorphous CAP with its release time scale for a small organic molecule, the same category to which antibiotics belong, of 1-2 months under the conditions applied in our experiments. By combining these different CAP phases in various proportions, drug release profiles could be tailored to the therapeutic occasion. PMID:23115118

Uskokovi?, Vuk; Desai, Tejal A

2012-10-31

291

Targeted and intracellular triggered delivery of therapeutics to cancer cells and the tumor microenvironment: impact on the treatment of breast cancer.  

PubMed

Limiting tumor invasion to the surrounding healthy tissues has proven to be clinically relevant for anticancer treatment options. We have demonstrated that, within a solid tumor, it is possible to achieve such a goal with the same nanoparticle by intracellular and triggered targeted drug delivery to more than one cell population. We have identified the nucleolin receptor in endothelial and cancer cells in tissue samples from breast cancer patients, which enabled the design of a F3-peptide-targeted sterically stabilized pH-sensitive liposome. The clinical potential of such strategy was demonstrated by the successful specific cellular association by breast cancer cells harvested from tumors of patients submitted to mastectomy. In vitro, the nanoparticle targeted the nucleolin receptor on a cell and ligand-specific manner and improved cytotoxicity of doxorubicin (used as a model drug) towards breast cancer and endothelial cells by 177- and 162-fold, respectively, relative to the commercially available non-targeted non-pH-sensitive liposomes. Moreover, active accumulation of F3-targeted pH-sensitive liposomes into human orthotopic tumors, implanted in the mammary fat pad of nude mice, was registered for a time point as short as 4 h, reaching 48% of the injected dose/g of tissue. Twenty-four hours post-injection the accumulation of the dual-targeted pH-sensitive nanoparticle in the tumor tissue was 33-fold higher than the non-targeted non-pH-sensitive counterpart. In mice treated with the developed targeted nanoparticle significant decrease of the tumor viable rim area and microvascular density, as well as limited invasion to surrounding healthy tissues were observed (as opposed to other tested controls), which may increase the probability of tumors falling in the category of "negative margins" with reduced risk of relapse. PMID:21805188

Moura, Vera; Lacerda, Manuela; Figueiredo, Paulo; Corvo, Maria L; Cruz, Maria E M; Soares, Raquel; de Lima, Maria C Pedroso; Simões, Sérgio; Moreira, João N

2011-07-30

292

Accurate Accident Reconstruction in VANET  

Microsoft Academic Search

\\u000a We propose a forensic VANET application to aid an accurate accident reconstruction. Our application provides a new source\\u000a of objective real-time data impossible to collect using existing methods. By leveraging inter-vehicle communications, we compile\\u000a digital evidence describing events before, during, and after an accident in its entirety. In addition to sensors data and\\u000a major components’ status, we provide relative positions

Yuliya Kopylova; Csilla Farkas; Wenyuan Xu

293

Accelerated Partial Breast Irradiation: Using the CyberKnife as the Radiation Delivery Platform in the Treatment of Early Breast Cancer  

PubMed Central

We evaluate the CyberKnife (Accuray Incorporated, Sunnyvale, CA, USA) for non-invasive delivery of accelerated partial breast irradiation (APBI) in early breast cancer patients. Between 6/2009 and 5/2011, nine patients were treated with CyberKnife APBI. Normal tissue constraints were imposed as outlined in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 (NSABP/RTOG) Protocol (Vicini and White, 2007). Patients received a total dose of 30?Gy in five fractions (group 1, n?=?2) or 34?Gy in 10 fractions (group 2, n?=?7) delivered to the planning treatment volume (PTV) defined as the clinical target volume (CTV) +2?mm. The CTV was defined as either the lumpectomy cavity plus 10?mm (n?=?2) or 15?mm (n?=?7). The cavity was defined by a T2-weighted non-contrast breast MRI fused to a planning non-contrast thoracic CT. The CyberKnife Synchrony system tracked gold fiducials sutured into the cavity wall during lumpectomy. Treatments started 4–5?weeks after lumpectomy. The mean PTV was 100?cm3 (range, 92–108?cm3) and 105?cm3 (range, 49–241?cm3) and the mean PTV isodose prescription line was 70% for groups 1 and 2, respectively. The mean percent of whole breast reference volume receiving 100 and 50% of the dose (V100 and V50) for group 1 was 11% (range, 8–13%) and 23% (range, 16–30%) and for group 2 was 11% (range, 7–14%) and 26% (range, 21–35.0%), respectively. At a median 7?months follow-up (range, 4–26?months), no acute toxicities were seen. Acute cosmetic outcomes were excellent or good in all patients; for those patients with more than 12?months follow-up the late cosmesis outcomes were excellent or good. In conclusion, the lack of observable acute side effects and current excellent/good cosmetic outcomes is promising. We believe this suggests the CyberKnife is a suitable non-invasive radiation platform for delivering APBI with achievable normal tissue constraints.

Vermeulen, Sandra; Cotrutz, Cristian; Morris, Astrid; Meier, Robert; Buchanan, Claire; Dawson, Patricia; Porter, Bruce

2011-01-01

294

More accurate time from the Heathkit most accurate clock  

NASA Astrophysics Data System (ADS)

The addition of an auxiliary circuit to the Heathkit GC-1000 clock is described. The circuit, which consists of two integrated circuits, two resistors, and three capacitors, will supply a more accurate timing pulse to the computer. The circuit contains two input signals and produces one output; the inputs are multiplexed seven-digit displays (two digits for hour, minute, and second, and one for tenths of a second) and the output appears as a string of about 10 low-going pulses about 1.25 ms in duration. Low pass filters (R1 and C1) are utilized to eliminate extraneous pulses. The materials and procedures for attaching the circuit to the clock are examined. The software for the data set ready signal, and the method for accurate timing of data collection are discussed. The accuracy of the clock is evaluated and it is observed that the circuit improves the correct time provided by the clock from + or - 29 ms to + or - 5 ms.

Tollefson, M. V.; Bloomer, R. H., Jr.

1986-05-01

295

A robust MRI-compatible system to facilitate highly accurate stereotactic administration of therapeutic agents to targets within the brain of a large animal model  

Microsoft Academic Search

Achieving accurate intracranial electrode or catheter placement is critical in clinical practice in order to maximise the efficacy of deep brain stimulation and drug delivery respectively as well as to minimise side-effects. We have developed a highly accurate and robust method for MRI-guided, stereotactic delivery of catheters and electrodes to deep target structures in the brain of pigs. This study

E. White; M. Woolley; A. Bienemann; D. E. Johnson; M. Wyatt; G. Murray; H. Taylor; S. S. Gill

2011-01-01

296

38 CFR 4.46 - Accurate measurement.  

Code of Federal Regulations, 2013 CFR

...RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.46 Accurate measurement. Accurate measurement...examinations conducted within the Department of Veterans Affairs. Muscle atrophy must also be accurately measured and reported....

2013-07-01

297

Chronotherapeutic drug delivery.  

PubMed

Living organisms follow a circadian rhythm in which physiological processes such as hormonal secretion, metabolism, heart rate, and renal output are affected by the time of day. Chronotherapy coordinates drug delivery with the circadian rhythm to enhance effectiveness and mitigate adverse effects and is achieved by delivering a drug when the system is most susceptible. Cancer is a chronotherapeutic disorder. Cancer treatment requires high doses of intravenous medication to kill cancerous cells; however, normal cells are also killed, creating intolerable side effects. This review shows that chronotherapy can play a vital role in the quality of life and survival rate for oncology patients. PMID:22955155

Librodo, Paul; Buckley, Mitchell; Luk, Marilyn; Bisso, Andrea

298

Development and evaluation of colloidal modified nanolipid carrier: application to topical delivery of tacrolimus, Part II - in vivo assessment, drug targeting, efficacy, and safety in treatment for atopic dermatitis.  

PubMed

In atopic dermatitis (AD), topical anti-inflammatory therapy with skin barrier restoration to prevent repeated inflammatory episodes leads to long-term therapeutic success. Tacrolimus, although effective against AD, is a challenging molecule due to low solubility, low-penetration, poor-bioavailability, and toxicity. Part I of this paper, reported novel modified nanolipid carrier system for topical delivery of tacrolimus (T-MNLC), offering great opportunity to load low-solubility drug with improved entrapment efficiency, enhanced stability and improved skin deposition. Present investigation focused on restoration of skin barrier, site-specific delivery, therapeutic effectiveness, and safety of novel T-MNLC. T-MNLC greatly enhanced occlusive properties, skin hydration potential and reduced transepidermal water loss. This might help to reduce the number of flares and better control the disease. Cutaneous uptake and drug deposition in albino rats by HPLC and confocal laser scanning microscopy revealed prominently elevated drug levels in all skin strata with T-MNLC as compared to reference. T-MNLC demonstrated efficient suppression of inflammatory responses in BALB/c mice model of AD. Safety assessment by acute and repeated-dose dermal toxicity demonstrated mild keratosis and collagenous mass infiltration at the treatment area with repeated application of reference. Interestingly, T-MNLC showed no evident toxicity exhibiting safe drug delivery. Thus, novel T-MNLC would be a safe, effective, and esthetically appealing alternative to conventional vehicles for treatment for AD. PMID:23246619

Pople, Pallavi V; Singh, Kamalinder K

2012-12-12

299

Forceps Delivery  

MedlinePLUS

... imperfecta, or has a bleeding disorder, such as hemophilia Your baby's head hasn't yet moved past ... ring rather than a hard surface. Consider complementary treatments. Some research suggests that lavender might help relieve ...

300

Characterization of responses of 2d array seven29 detector and its combined use with octavius phantom for the patient-specific quality assurance in rapidarc treatment delivery  

SciTech Connect

A commercial 2D array seven29 detector has been characterized and its performance has been evaluated. 2D array ionization chamber equipped with 729 ionization chambers uniformly arranged in a 27 Multiplication-Sign 27 matrix with an active area of 27 Multiplication-Sign 27 cm{sup 2} was used for the study. An octagon-shaped phantom (Octavius Phantom) with a central cavity is used to insert the 2D ion chamber array. All measurements were done with a linear accelerator. The detector dose linearity, reproducibility, output factors, dose rate, source to surface distance (SSD), and directional dependency has been studied. The performance of the 2D array, when measuring clinical dose maps, was also investigated. For pretreatment quality assurance, 10 different RapidArc plans conforming to the clinical standards were selected. The 2D array demonstrates an excellent short-term output reproducibility. The long-term reproducibility was found to be within {+-}1% over a period of 5 months. Output factor measurements for the central chamber of the array showed no considerable deviation from ion chamber measurements. We found that the 2D array exhibits directional dependency for static fields. Measurement of beam profiles and wedge-modulated fields with the 2D array matched very well with the ion chamber measurements in the water phantom. The study shows that 2D array seven29 is a reliable and accurate dosimeter and a useful tool for quality assurance. The combination of the 2D array with the Octavius phantom proved to be a fast and reliable method for pretreatment verification of rotational treatments.

Syamkumar, S.A., E-mail: skppm@rediffmail.com [Department of Medical Physics, Cancer Institute (WIA), Chennai (India); Padmanabhan, Sriram; Sukumar, Prabakar; Nagarajan, Vivekanandan [Department of Medical Physics, Cancer Institute (WIA), Chennai (India)

2012-04-01

301

Delivery system for molten salt oxidation of solid waste  

Microsoft Academic Search

The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a

William A. Brummond; Dwight V. Squire; Jeffrey A. Robinson; Palmer A. House

2002-01-01

302

Measurements of lateral penumbra for uniform scanning proton beams under various beam delivery conditions and comparison to the XiO treatment planning system.  

PubMed

Purpose: The main purposes of this study were to (1) investigate the dependency of lateral penumbra (80%-20% distance) of uniform scanning proton beams on various factors such as air gap, proton range, modulation width, compensator thickness, and depth, and (2) compare the lateral penumbra calculated by a treatment planning system (TPS) with measurements.Methods: First, lateral penumbra was measured using solid-water phantom and radiographic films for (a) air gap, ranged from 0 to 35 cm, (b) proton range, ranged from 8 to 30 cm, (c) modulation, ranged from 2 to 10 cm, (d) compensator thickness, ranged from 0 to 20 cm, and (e) depth, ranged from 7 to 15 cm. Second, dose calculations were computed in a virtual water phantom using the XiO TPS with pencil beam algorithm for identical beam conditions and geometrical configurations that were used for the measurements. The calculated lateral penumbra was then compared with the measured one for both the horizontal and vertical scanning magnets of our uniform scanning proton beam delivery system.Results: The results in the current study showed that the lateral penumbra of horizontal scanning magnet was larger (up to 1.4 mm for measurement and up to 1.0 mm for TPS) compared to that of vertical scanning magnet. Both the TPS and measurements showed an almost linear increase in lateral penumbra with increasing air gap as it produced the greatest effect on lateral penumbra. Lateral penumbra was dependent on the depth and proton range. Specifically, the width of lateral penumbra was found to be always lower at shallower depth than at deeper depth within the spread out Bragg peak (SOBP) region. The lateral penumbra results were less sensitive to the variation in the thickness of compensator, whereas lateral penumbra was independent of modulation. Overall, the comparison between the results of TPS with that of measurements indicates a good agreement for lateral penumbra, with TPS predicting higher values compared to measurements.Conclusions: Lateral penumbra of uniform scanning proton beams depends on air gap, proton range, compensator thickness, and depth, whereas lateral penumbra is not dependent on modulation. The XiO TPS typically overpredicted lateral penumbra compared to measurements, within 1 mm for most cases, but the difference could be up to 2.5 mm at a deep depth and large air gap. PMID:24007141

Rana, Suresh; Zeidan, Omar; Ramirez, Eric; Rains, Michael; Gao, Junfang; Zheng, Yuanshui

2013-09-01

303

Intra-Arterial Catheter for Drug Delivery.  

National Technical Information Service (NTIS)

The present invention provides a catheter, a drug delivery system and methods for the localized delivery of therapeutic or diagnostic agent to a target location in a subject and methods for the treatment of a pathological disorder in a subject using the s...

S. Joshi

2004-01-01

304

COLON TARGETED DRUG DELIVERY SYSTEMS  

Microsoft Academic Search

Colon targeted drug delivery systems have the potential to deliver drugs for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. In recent years, various pharmaceutical approaches have been developed for targeting the drugs to the colon include, formation of prodrugs, coating of pH-sensitive polymers, use of colon

Ceyda Tuba

305

Accurate Targeting of Liver Tumors in Stereotactic Radiation Therapy  

Microsoft Academic Search

This doctoral thesis concerns the treatment of liver cancer patients using\\u000aexternal beam radiotherapy. The quality of this treatment greatly depends\\u000aon delivering a high radiation dose to the tumor while keeping the dose as\\u000alow as possible to surrounding healthy tissues. One of the major\\u000achallenges is locating the tumor at the moment of dose delivery. In this \\u000aork,

W. Wunderink

2011-01-01

306

Physically facilitating drug-delivery systems  

PubMed Central

Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years.

Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

2012-01-01

307

Transdermal drug delivery  

Microsoft Academic Search

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted

Mark R Prausnitz; Robert Langer

2008-01-01

308

An Extension of the `MLR' Potential Function Form which Allows for AN Accurate Dpf Treatment of Li_2(1^3?^+_g), which Couples to Two Other States Near Their Asymptotes  

NASA Astrophysics Data System (ADS)

The only potential energy functions for the 1^3?^+_g state of Li_2 published to date were conventional RKR curves based on experimental data for the vibrational levels v=1-7, and they do not yield realistic predictions for the very weakly bound levels v=62 - 89 for ^{7,7}Li_2 and v=59 - 79 for ^{6,6}Li_2, which were subsequently observed using photoassociation spectroscopy (PAS). A recent analysis of data for the 1 ^3?_g^+ -a ^3?_u^+ and 2 ^3?_g -a ^3?_u^+ systems of Li_2 was unable to incorporate these PAS data, and this was due to the lack of a potential function form with the ability to accurately describe the behaviour of the potential for a molecule which becomes coupled to two other distinct states near the dissociation asymptote. The current work presents and tests an extension of the `Morse/Long-Range' (MLR) potential function form which does provide an accurate description of the 1^3?^+_g- state potential at all internuclear distances, including the long-range region where the three-state coupling occurs. The extension is based on expressions reported by Aubert-Frécon and co-workers, which show that the long-range tail of this potential is one of the eigenvalues of a 3x3 Hamiltonian matrix. Accordingly, this extension requires the diagonalization of this matrix at each internuclear distance r. Although this can be done analytically, we show that the diagonalization is in fact computed more efficiently numerically, and leads to a more accurate potential energy function. F. Martin et al., Spectrochimica Acta 44A, 1369 (1988) C. Linton et al., J. Chem. Phys. 91, 6036 (1989). W.I. McAlexander et al., Phys. Rev. A 51, R871 (1995) E.R.I. Abraham et al. J. Chem. Phys. 103, 7773 (1995) N.S. Dattani, et al., 63rd Ohio State University Int. Symp. on Molec. Spec. (2008), paper RC11. R.J. Le Roy and R.D.E. Henderson, Mol. Phys. 105, 663 (2007) R.J. Le Roy et al., J. Chem. Phys. (2009, submitted). Martin et al., Phys, Rev. A 55, 3458 (1997) M. Aubert-Frecon et al., J. Mol. Spectrosc. 192, 239 (1998).

Dattani, Nikesh S.; Le Roy, Robert J.; Ross, Amanda J.; Linton, Colan

2009-06-01

309

Targeted Spinal Cord Therapeutics Delivery: Stabilized Platform and Microelectrode Recording Guidance Validation  

Microsoft Academic Search

Background\\/Aims: No validated delivery technique exists for accurate, reproducible delivery of biological therapies to discrete spinal cord targets. To address this unmet need, we have constructed a stabilized platform capable of supporting physiologic mapping, through microelectrode recording, and cellular or viral payload delivery to the ventral horn. Methods: A porcine animal model (n = 7) has been chosen based upon

Jonathan Riley; John Butler; Kenneth B. Baker; Shearwood McClelland III; Qingshan Teng; Jun Yang; Mary Garrity-Moses; Thais Federici; Nicholas M. Boulis

2008-01-01

310

Nanoparticles as 'smart' pharmaceutical delivery.  

PubMed

Pharmaceuticals in conjunction with nanoparticle delivery systems are growing towards new heights. The aim of this review is to gain a thorough understanding of different types and characteristics of nanoparticle based delivery systems, important properties of delivery systems, pharmaceutical ingredient loading and release in the nanoparticle delivery systems. In this review, we have also highlighted about the promising pharmaceutical deliveries like brain targeted delivery, ocular delivery, oral delivery, dermal and transdermal delivery, cancer chemotherapy, vaccine delivery, nucleic acids delivery and delivery system coupling to implants. A snapshot of the nanoparticle mediated drug deliveries which are commercially available and ongoing clinical trials have been provided. PMID:23747865

Chakraborty, Chiranjib; Pal, Soumen; Doss, George Priya C; Wen, Zhi-Hong; Lin, Chan-Shing

2013-06-01

311

Accurate ab Initio Spin Densities  

PubMed Central

We present an approach for the calculation of spin density distributions for molecules that require very large active spaces for a qualitatively correct description of their electronic structure. Our approach is based on the density-matrix renormalization group (DMRG) algorithm to calculate the spin density matrix elements as a basic quantity for the spatially resolved spin density distribution. The spin density matrix elements are directly determined from the second-quantized elementary operators optimized by the DMRG algorithm. As an analytic convergence criterion for the spin density distribution, we employ our recently developed sampling-reconstruction scheme [J. Chem. Phys.2011, 134, 224101] to build an accurate complete-active-space configuration-interaction (CASCI) wave function from the optimized matrix product states. The spin density matrix elements can then also be determined as an expectation value employing the reconstructed wave function expansion. Furthermore, the explicit reconstruction of a CASCI-type wave function provides insight into chemically interesting features of the molecule under study such as the distribution of ? and ? electrons in terms of Slater determinants, CI coefficients, and natural orbitals. The methodology is applied to an iron nitrosyl complex which we have identified as a challenging system for standard approaches [J. Chem. Theory Comput.2011, 7, 2740].

2012-01-01

312

How accurate is peer grading?  

PubMed

Previously we showed that weekly, written, timed, and peer-graded practice exams help increase student performance on written exams and decrease failure rates in an introductory biology course. Here we analyze the accuracy of peer grading, based on a comparison of student scores to those assigned by a professional grader. When students graded practice exams by themselves, they were significantly easier graders than a professional; overall, students awarded ?25% more points than the professional did. This difference represented ?1.33 points on a 10-point exercise, or 0.27 points on each of the five 2-point questions posed. When students graded practice exams as a group of four, the same student-expert difference occurred. The student-professional gap was wider for questions that demanded higher-order versus lower-order cognitive skills. Thus, students not only have a harder time answering questions on the upper levels of Bloom's taxonomy, they have a harder time grading them. Our results suggest that peer grading may be accurate enough for low-risk assessments in introductory biology. Peer grading can help relieve the burden on instructional staff posed by grading written answers-making it possible to add practice opportunities that increase student performance on actual exams. PMID:21123695

Freeman, Scott; Parks, John W

2010-01-01

313

How Accurate Is Peer Grading?  

PubMed Central

Previously we showed that weekly, written, timed, and peer-graded practice exams help increase student performance on written exams and decrease failure rates in an introductory biology course. Here we analyze the accuracy of peer grading, based on a comparison of student scores to those assigned by a professional grader. When students graded practice exams by themselves, they were significantly easier graders than a professional; overall, students awarded ?25% more points than the professional did. This difference represented ?1.33 points on a 10-point exercise, or 0.27 points on each of the five 2-point questions posed. When students graded practice exams as a group of four, the same student-expert difference occurred. The student-professional gap was wider for questions that demanded higher-order versus lower-order cognitive skills. Thus, students not only have a harder time answering questions on the upper levels of Bloom's taxonomy, they have a harder time grading them. Our results suggest that peer grading may be accurate enough for low-risk assessments in introductory biology. Peer grading can help relieve the burden on instructional staff posed by grading written answers—making it possible to add practice opportunities that increase student performance on actual exams.

Parks, John W.

2010-01-01

314

Ultrahighly accurate 3D profilometer  

NASA Astrophysics Data System (ADS)

We have developed an Ultrahigh-Accurate 3-D Profilometer (UA3P), which, using a new, in-house-developed atomic force probe, has an accuracy of 10 nm. It is capable of measuring corners as small as 2 micro meter in radius and can cover an area up to 400 x 400 x 90 (mm), providing a powerful boost to nano-level processing. A commercial product was introduced in 1994. Examples of the key components made possible by this technology include aspherical lenses (used for a Blu-ray Disc device, a next-generation DVD, digital cameras, cellular phones, optical communications), free form lenses (used for frennel lens common to CD and DVD, laser printer lens, multi focus glass lens, cubic phase plate to extend depth of focus), gigabit semiconductor wafers, hard discs, air conditioner scroll vanes, DVC cylinders. The premiere ultra high-precision three-dimensional profilometer delivers superb performance using a variety of micro-measurements for a wide range of applications.

Tsutsumi, Hideki; Yoshizumi, Keiichi; Takeuchi, Hiroyuki

2005-02-01

315

Nanobiotechnology-Based Drug Delivery to the Central Nervous System  

Microsoft Academic Search

Background: Drug delivery across the blood-brain barrier (BBB) is a major limitation in the treatment of central nervous system (CNS) disorders. Several approaches are being investigated to improve drug delivery across the BBB. Objective\\/Methods: This review deals with the role of nanobiotechnology in CNS drug delivery. The small size of the nanoparticles enables them to penetrate the BBB and facilitate

K. K. Jain

2007-01-01

316

Pulmonary drug delivery systems for antimicrobial agents: facts and myths  

Microsoft Academic Search

Inhaled antimicrobial agents are used for the treatment of respiratory tract infections due to Gram-negative bacteria, mainly Pseudomonas aeruginosa. The effectiveness of the inhaled antimicrobial therapy is believed to correlate with the delivery system used. The objective of this review was to search for data supporting differentiation in clinical effectiveness between systems used for pulmonary delivery of antibiotics, including delivery

Matthew E. Falagas; Argyris Michalopoulos; Eugenios I. Metaxas

2010-01-01

317

Successful treatment of osseous lesion associated with palatoradicular groove using local drug delivery and guided tissue regeneration: A report of two cases  

PubMed Central

Developmental grooves are not rare and often appear on maxillary lateral and central incisors and are an important predisposing factor to localized periodontal disease. Various techniques have been adopted to eliminate the groove and regenerate lost periodontium. This report of two cases describes the technique of using the local drug delivery system with chlorehexidine and the guided tissue regeneration (GTR) to control the disease progression and regeneration.

Gadagi, Jayaprakash S.; Elavarasu, Sugumari; Ananda, Divya; Murugan, Thamaraiselvan

2012-01-01

318

What is the best treatment for fluctuating Parkinson’s disease: continuous drug delivery or deep brain stimulation of the subthalamic nucleus?  

Microsoft Academic Search

Motor complications impair quality of life and cause severe disability in patients with advanced Parkinson’s disease (PD).\\u000a Since they are often refractory to medical therapy, interventional therapies have been developed, which can provide a considerable\\u000a reduction of daily off-time and dopaminergic dyskinesias. Continuous dopaminergic drug delivery (CDD) is based on the steady\\u000a stimulation of striatal dopamine receptors by subcutaneous apomorphine

Rüdiger Hilker; Angelo Antonini; Per Odin

2011-01-01

319

A thermally responsive biopolymer for intra-articular drug delivery  

Microsoft Academic Search

Intra-articular drug delivery is the preferred standard for targeting pharmacologic treatment directly to joints to reduce undesirable side effects associated with systemic drug delivery. In this study, a biologically based drug delivery vehicle was designed for intra-articular drug delivery using elastin-like polypeptides (ELPs), a biopolymer composed of repeating pentapeptides that undergo a phase transition to form aggregates above their transition

Helawe Betre; Wenge Liu; Michael R. Zalutsky; Ashutosh Chilkoti; Virginia B. Kraus; Lori A. Setton

2006-01-01

320

4D imaging and 4D radiation therapy: a New Era of therapy design and delivery.  

PubMed

Recently developed 4D CT imaging technologies have shown that significant organ motion can occur within radiotherapy fields during treatment. Most often a result of respiration, this motion can cause dose delivery errors that are clinically significant when unmanaged, as demonstrated in many recent investigations. Motion during the regular breathing cycling is important, but day-to-day breathing variations, as may be caused by changes in residual tidal volume, can cause systematic shifts in tumor position. These may cause delivery misalignments because the tumor is not in the same average location at each treatment. Approaches to management of this motion may involve motion-inclusive planning, gating or tracking. 4D CT has been instrumental in most of these approaches. Given the state of treatment planning software, it is not possible to preplan whether a specific patient would benefit from one or another of these methods. Daily imaging (or use of a nonimage-based system such as Calypso) is necessary to locate the tumor, and the location must be correlated with measurements from a system that tracks breathing motion during treatment delivery. This is typically done using an independent metric that characterizes the breathing cycle (e.g. the height of the abdomen). Only then can the treatment plan be accurately implemented. There are many methods to manage tumor motion, though most are challenging to implement and remain poorly supported by vendors. When determining which system to use, an important distinction between competing approaches is whether they are amplitude- or phase-based. Some implementations may use different approaches for different parts of the treatment planning and delivery process, potentially introducing errors in the characterization of breathing motion. While many advances have been achieved and are discussed here, the development of solid, stable and robust processes to effectively manage breathing motion remains a foremost and continuing challenge in radiotherapy. PMID:21625150

Low, Daniel

2011-05-20

321

Dental Delivery Systems Terminology.  

National Technical Information Service (NTIS)

In order to facilitate communications among those involved in the study of dental services delivery the Delivery Systems Branch, Division of Dentistry prepared this glossary of the terms they use. They define dental health services as nonclinical services...

1976-01-01

322

Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.  

PubMed

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III. PMID:18045346

Jahnke, A; Hirschberger, J; Fischer, C; Brill, T; Köstlin, R; Plank, C; Küchenhoff, H; Krieger, S; Kamenica, K; Schillinger, U

2007-12-01

323

Drug delivery systems from nose to brain.  

PubMed

The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed. PMID:23016642

Misra, Ambikanandan; Kher, Gitanjali

2012-09-01

324

Verification of helical tomotherapy delivery using autoassociative kernel regression  

SciTech Connect

Quality assurance (QA) is a topic of major concern in the field of intensity modulated radiation therapy (IMRT). The standard of practice for IMRT is to perform QA testing for individual patients to verify that the dose distribution will be delivered to the patient. The purpose of this study was to develop a new technique that could eventually be used to automatically evaluate helical tomotherapy treatments during delivery using exit detector data. This technique uses an autoassociative kernel regression (AAKR) model to detect errors in tomotherapy delivery. AAKR is a novel nonparametric model that is known to predict a group of correct sensor values when supplied a group of sensor values that is usually corrupted or contains faults such as machine failure. This modeling scheme is especially suited for the problem of monitoring the fluence values found in the exit detector data because it is able to learn the complex detector data relationships. This scheme still applies when detector data are summed over many frames with a low temporal resolution and a variable beam attenuation resulting from patient movement. Delivery sequences from three archived patients (prostate, lung, and head and neck) were used in this study. Each delivery sequence was modified by reducing the opening time for random individual multileaf collimator (MLC) leaves by random amounts. The error and error-free treatments were delivered with different phantoms in the path of the beam. Multiple autoassociative kernel regression (AAKR) models were developed and tested by the investigators using combinations of the stored exit detector data sets from each delivery. The models proved robust and were able to predict the correct or error-free values for a projection, which had a single MLC leaf decrease its opening time by less than 10 msec. The model also was able to determine machine output errors. The average uncertainty value for the unfaulted projections ranged from 0.4% to 1.8% of the detector signal. The low model uncertainty indicates that the AAKR model is extremely accurate in its predictions and also suggests that the model may be able to detect errors that cause the fluence to change by less than 2%. However, additional evaluation of the AAKR technique is needed to determine the minimum detectable error threshold from the compressed helical tomotherapy detector data. Further research also needs to explore applying this technique to electronic portal imaging detector data.

Seibert, Rebecca M.; Ramsey, Chester R.; Garvey, Dustin R.; Wesley Hines, J.; Robison, Ben H.; Outten, Samuel S. [Department of Nuclear Engineering, The University of Tennessee, Knoxville, Tennessee 37996 and Department of Radiation Oncology, Thompson Cancer Survival Center, Knoxville, Tennessee 37916 (United States); Department of Nuclear Engineering, The University of Tennessee, Knoxville, Tennessee 37996 (United States); Department of Nuclear Engineering, The University of Tennessee, Knoxville, Tennessee 37996 and Department of Radiation Oncology, Thompson Cancer Survival Center, Knoxville, Tennessee 37916 (United States); Department of Radiation Oncology, Thompson Cancer Survival Center, Knoxville, Tennessee 37916 (United States)

2007-08-15

325

Gene Expression Profiling Can Accurately Diagnose Burkitt's Lymphoma  

Cancer.gov

Gene profiling, a molecular technique that examines many genes simultaneously, can accurately distinguish between two types of immune cell tumors, Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL). Burkitt's lymphoma and DLBCL appear similar when viewed under a microscope but correct diagnosis is critical because each requires very different treatments.

326

Mobile Drug-Delivery for Ambient Assisted Living: Implantable and Extracorporeal Devices  

Microsoft Academic Search

Miniaturized smart drug delivery devices pave the way for a personalized treatment of many diseases by un- skilled persons outside the hospital. Many therapies require a repetitive delivery of a defined amount of drug in well defined time slots. Innovative drug delivery systems constitute an important prerequisite for ambient as- sisted living: The reliable delivery of drugs, in time and

S. Haeberle; R. Gronmaier; T. Goettsche; M Vosseler; A. Kain; M. Reiterer; D. Hradetzky; C. Mueller; S. Messner; R. Zengerle

327

Formulations for trans-tympanic antibiotic delivery.  

PubMed

We have developed a drug delivery system for prolonged trans-tympanic antibiotic delivery from a single dose administration. Increased permeability to ciprofloxacin of the intact tympanic membrane (TM) was achieved by chemical permeation enhancers (CPEs--bupivacaine, limonene, sodium dodecyl sulfate); this was also seen by CPEs contained within a hydrogel (poloxamer 407) to maintain the formulation at the TM. The CPE-hydrogel formulation had minimal effects on auditory thresholds and tissue response in vivo. CPE-hydrogel formulations have potential for ototopical delivery of ciprofloxacin for the treatment of acute otitis media (AOM) and other middle ear diseases. PMID:23146430

Khoo, Xiaojuan; Simons, Emmanuel J; Chiang, Homer H; Hickey, Julia M; Sabharwal, Vishakha; Pelton, Stephen I; Rosowski, John J; Langer, Robert; Kohane, Daniel S

2012-11-09

328

Influence of heat treatment on spray-dried mixtures of Amioca starch and Carbopol 974P used as carriers for nasal drug delivery.  

PubMed

A mucoadhesive spray-dried starch/poly(acrylic acid) powder underwent different heat treatments in order to induce cross-linking between the functional groups of starch (Amioca) and poly(acrylic acid) (Carbopol 974P). After heat treatment the water-absorbing capacity, viscosity and elasticity of the mucoadhesive powder increased. NMR analysis in combination with FT-IR indicated that heat treatment induced a low degree of cross-linking between the polymers. Nasal administration of Amioca/Carbopol 974P powders without heat treatment resulted in an absolute bioavailability in rabbits of 8.2+/-3.0% for insulin. Due to the difference in water-absorbing capacity (which opened the tight junctions of the nasal mucosa), elasticity and plasticity (which reduced mucociliairy clearance and prolonged residence time) heat treatment at 120 degrees C improved the bioavailability: 26.4+/-21.9, 36.5+/-11.0 and 19.3+/-17.3% after heat treatment during 30 min, 1 h and 4 h, respectively. Heat treatment at 60 degrees C was less efficient. This study demonstrated that the nasal insulin absorption improved via heat treatment of the Amioca/Carbopol 974P powder (prior to the addition of insulin). The bioavailability-enhancing effect of a 1 h heat treatment at 120 degrees C was confirmed using the same polymer matrix in combination with different drugs (salmon calcitonin, human growth hormone and metoprolol tartrate). PMID:19477256

Coucke, D; Pringels, E; Foreman, P; Adriaensens, P; Carleer, R; Remon, J P; Vervaet, C

2009-05-27

329

Colloidal drug delivery systems in vaccine delivery.  

PubMed

Vaccines play a vital role in the field of community medicine to combat against several diseases of human existence. Vaccines primarily trigger the acquired immune system to develop long-lasting immunity against pathogens. Conventional approaches for vaccine delivery lacks potential to target a particular antigen to develop acquired immunity by specific antibodies. Recent advancements in vaccine delivery showed that inclusion of adjuvants in vaccine formulations or delivery of them in a carrier helps in achieving desired targeting ability, reducing the immunogenicity and significant augmentation in the immune response. Colloidal carriers (liposomes, niosomes, microspheres, proteosomes, virosomes and virus like particles (VLPs), antigen cochleates, dendrimers and carbon nanotubes) have been widely explored for vaccine delivery. Further, surface engineering of these carriers with ligands, functional moieties and monoclonal antibodies tend to enhance the immune recognition potential of vaccines by differentiation of antigen specific memory T-cells. The current review, therefore, provides an updated account on the recent advancements in various colloidal delivery systems in vaccine delivery, outlining the mechanism of immune response initiated by them along with potential applications and marketed instances in an explicit manner. PMID:23072326

Beg, Sarwar; Samad, Abdus; Nazish, Iram; Sultana, Ruksar; Rahman, Mahfoozur; Ahmad, Md Zaki; Akbar, Md

2013-01-01

330

Temporal characterization and in vitro comparison of cell survival following the delivery of 3D-conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)  

NASA Astrophysics Data System (ADS)

A phantom was designed and implemented for the delivery of treatment plans to cells in vitro. Single beam, 3D-conformal radiotherapy (3D-CRT) plans, inverse planned five-field intensity-modulated radiation therapy (IMRT), nine-field IMRT, single-arc volumetric modulated arc therapy (VMAT) and dual-arc VMAT plans were created on a CT scan of the phantom to deliver 3 Gy to the cell layer and verified using a Farmer chamber, 2D ionization chamber array and gafchromic film. Each plan was delivered to a 2D ionization chamber array to assess the temporal characteristics of the plan including delivery time and 'cell's eye view' for the central ionization chamber. The effective fraction time, defined as the percentage of the fraction time where any dose is delivered to each point examined, was also assessed across 120 ionization chambers. Each plan was delivered to human prostate cancer DU-145 cells and normal primary AGO-1522b fibroblast cells. Uniform beams were delivered to each cell line with the delivery time varying from 0.5 to 20.54 min. Effective fraction time was found to increase with a decreasing number of beams or arcs. For a uniform beam delivery, AGO-1552b cells exhibited a statistically significant trend towards increased survival with increased delivery time. This trend was not repeated when the different modulated clinical delivery methods were used. Less sensitive DU-145 cells did not exhibit a significant trend towards increased survival with increased delivery time for either the uniform or clinical deliveries. These results confirm that dose rate effects are most prevalent in more radiosensitive cells. Cell survival data generated from uniform beam deliveries over a range of dose rates and delivery times may not always be accurate in predicting response to more complex delivery techniques, such as IMRT and VMAT.

McGarry, Conor K.; Butterworth, Karl T.; Trainor, Colman; O'Sullivan, Joe M.; Prise, Kevin M.; Hounsell, Alan R.

2011-04-01

331

Considerations in insulin delivery device selection.  

PubMed

Recent guidelines from the American Diabetes Association and the European Association for the Study of Diabetes promote the use of insulin sooner rather than later in patients with type 2 diabetes to achieve goal range glucose control (< 7%) but remain silent on a recommendation for delivery system. Even though there is widespread consensus among experts and payers that people with type 2 diabetes should use insulin earlier to achieve tight control, it still remains an elusive goal. Benefits of pen-type delivery devices include accurate dosing, faster and easier setting of dose and injection times, and increased patient acceptance and adherence. Before healthcare professionals can recommend a delivery device, it is critical they understand not only the medication in the device but also the various features and benefits to the different devices available and how those impact the patient. We will present considerations to assist in making appropriate device selection, to optimize patient success. PMID:20515315

Valentine, Virginia; Kruger, Davida F

2010-06-01

332

Accurate, reproducible measurement of blood pressure.  

PubMed Central

The diagnosis of mild hypertension and the treatment of hypertension require accurate measurement of blood pressure. Blood pressure readings are altered by various factors that influence the patient, the techniques used and the accuracy of the sphygmomanometer. The variability of readings can be reduced if informed patients prepare in advance by emptying their bladder and bowel, by avoiding over-the-counter vasoactive drugs the day of measurement and by avoiding exposure to cold, caffeine consumption, smoking and physical exertion within half an hour before measurement. The use of standardized techniques to measure blood pressure will help to avoid large systematic errors. Poor technique can account for differences in readings of more than 15 mm Hg and ultimately misdiagnosis. Most of the recommended procedures are simple and, when routinely incorporated into clinical practice, require little additional time. The equipment must be appropriate and in good condition. Physicians should have a suitable selection of cuff sizes readily available; the use of the correct cuff size is essential to minimize systematic errors in blood pressure measurement. Semiannual calibration of aneroid sphygmomanometers and annual inspection of mercury sphygmomanometers and blood pressure cuffs are recommended. We review the methods recommended for measuring blood pressure and discuss the factors known to produce large differences in blood pressure readings.

Campbell, N R; Chockalingam, A; Fodor, J G; McKay, D W

1990-01-01

333

Extending Use of Direct Behavior Rating beyond Student Assessment: Applications to Treatment Integrity Assessment within a Multi-Tiered Model of School-Based Intervention Delivery  

ERIC Educational Resources Information Center

|To make valid decisions about intervention effectiveness in a tiered intervention system, it is essential to formatively assess treatment integrity along with student outcomes. Despite significant advances in technologies for ongoing assessment of student outcomes, research regarding treatment integrity assessment has not shared the same progress…

Hagermoser Sanetti, Lisa M.; Chafouleas, Sandra M.; Christ, Theodore J.; Gritter, Katie L.

2009-01-01

334

Community-directed delivery of doxycycline for the treatment of onchocerciasis in areas of co-endemicity with loiasis in Cameroon  

Microsoft Academic Search

BACKGROUND: Severe side effects following ivermectin treatment of onchocerciasis in areas of co-endemicity with loaisis have been an impediment for the work of the African Programme for Onchocerciasis Control (APOC) in forested regions of several countries. Doxycycline has been shown to be effective in the treatment of onchocerciasis and has the added advantages of killing adult Onchocerca volvulus but neither

Samuel Wanji; Nicholas Tendongfor; Theolbald Nji; Mathias Esum; Julious N Che; Armand Nkwescheu; Fifen Alassa; Geremy Kamnang; Peter A Enyong; Mark J Taylor; Achim Hoerauf; David W Taylor

2009-01-01

335

Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer  

PubMed Central

Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly(å-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly(å-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of ?25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect.

Gao, Xiang; Wang, BiLan; Wei, XiaWei; Rao, Wang; Ai, Fang; Zhao, Fen; Men, Ke; Yang, Bowen; Liu, Xingyu; Huang, Meijuan; Gou, Maling; Qian, ZhiYong; Huang, Ning; Wei, Yuquan

2013-01-01

336

Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer.  

PubMed

Star-shaped polymer micelles have good stability against dilution with water, showing promising application in drug delivery. In this work, biodegradable micelles made from star-shaped poly(?-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer were prepared and used to deliver doxorubicin (Dox) in vitro and in vivo. First, an acrylated monomethoxy poly (ethylene glycol)-poly(?-caprolactone) (MPEG-PCL) diblock copolymer was synthesized, which then self-assembled into micelles, with a core-shell structure, in water. Then, the double bonds at the end of the PCL blocks were conjugated together by radical polymerization, forming star-shaped MPEG-PCL (SSMPEG-PCL) micelles. These SSMPEG-PCL micelles were monodispersed (polydispersity index = 0.11), with mean diameter of ?25 nm, in water. Blank SSMPEG-PCL micelles had little cytotoxicity and did not induce obvious hemolysis in vitro. The critical micelle concentration of the SSMPEG-PCL micelles was five times lower than that of the MPEG-PCL micelles. Dox was directly loaded into SSMPEG-PCL micelles by a pH-induced self-assembly method. Dox loading did not significantly affect the particle size of SSMPEG-PCL micelles. Dox-loaded SSMPEG-PCL (Dox/SSMPEG-PCL) micelles slowly released Dox in vitro, and the Dox release at pH 5.5 was faster than that at pH 7.0. Also, encapsulation of Dox in SSMPEG-PCL micelles enhanced the anticancer activity of Dox in vitro. Furthermore, the therapeutic efficiency of Dox/SSMPEG-PCL on colon cancer mouse model was evaluated. Dox/SSMPEG-PCL caused a more significant inhibitory effect on tumor growth than did free Dox or controls (P < 0.05), which indicated that Dox/SSMPEG-PCL had enhanced anticolon cancer activity in vivo. Analysis with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) showed that Dox/SSMPEG-PCL induced more tumor cell apoptosis than free Dox or controls. These results suggested that SSMPEG-PCL micelles have promising application in doxorubicin delivery for the enhancement of anticancer effect. PMID:23493403

Gao, Xiang; Wang, BiLan; Wei, XiaWei; Rao, Wang; Ai, Fang; Zhao, Fen; Men, Ke; Yang, Bowen; Liu, Xingyu; Huang, Meijuan; Gou, Maling; Qian, ZhiYong; Huang, Ning; Wei, Yuquan

2013-03-08

337

An Accurate Method for Measuring Activation Energy  

Microsoft Academic Search

In this letter, we present an accurate method for the measurement of activation energy. This method combined the excitation power dependent photoluminescence and temperature dependent photoluminescence together to obtain activation energy. We found with increasing temperature, there is a step transition from one emission mechanism to another. This step transition gives us an accurate measurement of activation energy. Using this

Xiang-Bai Chen; Jesse Huso; John L. Morrison; Leah Bergman

2005-01-01

338

Quantification of Horseradish Peroxidase Delivery into the Arterial Wall In Vivo as a Model of Local Drug Treatment: Comparison Between a Porous and a Gel-Coated Balloon Catheter  

Microsoft Academic Search

Purpose: To quantify horseradish peroxidase (HRP) delivery into the arterial wall, as a model of local drug delivery, and to compare two different percutaneous delivery balloons. Methods: Perforated and hydrophilic hydrogel-coated balloon catheters were used to deliver HRP in aqueous solution into the wall of porcine iliac arteries in vivo. HRP solutions of 1 mg\\/ml were used together with both

Armin Dick; Wolfgang Kromen; Eberhard Juengling; Stephanie Grosskortenhaus; Helmut Kammermeier; Dierk Vorwerk; Rolf W. Guenther

1999-01-01

339

Delivery system for molten salt oxidation of solid waste  

DOEpatents

The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

Brummond, William A. (Livermore, CA); Squire, Dwight V. (Livermore, CA); Robinson, Jeffrey A. (Manteca, CA); House, Palmer A. (Walnut Creek, CA)

2002-01-01

340

Optimal oxygen titration in patients with chronic obstructive pulmonary disease: a role for automated oxygen delivery?  

PubMed

Oxygen therapy can be life-saving for patients with chronic obstructive pulmonary disease (COPD) and is the backbone of any acute COPD treatment strategy. Although largely considered to be a benign drug, many publications have highlighted the need to accurately adjust oxygen delivery to avoid both hypoxemia and the problem of hyperoxia-induced hypercapnia. Recent clinical data have shown that the deleterious effects of excess oxygen treatment can not only alter carbon dioxide levels (which has been known for more than 60 years) but can also lead to an increase in mortality. Nevertheless, despite the extensive literature, the risks associated with hyperoxia are often overlooked and published clinical recommendations are largely ignored. This failure in knowledge translation has become increasingly important not only because of the desire to reduce medical error, but in a society with limited health care resources, the economic burden of COPD is such that it cannot afford to make preventable medical mistakes. Recently, novel devices have been developed to automatically adjust oxygen flow rates to maintain stable oxygen saturations. These closed-loop oxygen delivery systems have the potential to reduce medical error, improve morbidity and mortality, and reduce health care costs. Preliminary data in this field are promising and will require a significant amount of research in the coming years to determine the precise indications for these systems. The importance of appropriate oxygen dosing and the current literature regarding novel oxygen delivery systems are reviewed. PMID:23936881

Lellouche, François; Lipes, Jed; L'Her, Erwan

341

Oral insulin delivery: how far are we?  

PubMed

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The mainbarriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

2013-03-01

342

Nanoparticles as Smart Treatment-delivery Systems in Plants: Assessment of Different Techniques of Microscopy for their Visualization in Plant Tissues  

PubMed Central

Background and Aims The great potential of using nanodevices as delivery systems to specific targets in living organisms was first explored for medical uses. In plants, the same principles can be applied for a broad range of uses, in particular to tackle infections. Nanoparticles tagged to agrochemicals or other substances could reduce the damage to other plant tissues and the amount of chemicals released into the environment. To explore the benefits of applying nanotechnology to agriculture, the first stage is to work out the correct penetration and transport of the nanoparticles into plants. This research is aimed (a) to put forward a number of tools for the detection and analysis of core-shell magnetic nanoparticles introduced into plants and (b) to assess the use of such magnetic nanoparticles for their concentration in selected plant tissues by magnetic field gradients. Methods Cucurbita pepo plants were cultivated in vitro and treated with carbon-coated Fe nanoparticles. Different microscopy techniques were used for the detection and analysis of these magnetic nanoparticles, ranging from conventional light microscopy to confocal and electron microscopy. Key Results Penetration and translocation of magnetic nanoparticles in whole living plants and into plant cells were determined. The magnetic character allowed nanoparticles to be positioned in the desired plant tissue by applying a magnetic field gradient there; also the graphitic shell made good visualization possible using different microscopy techniques. Conclusions The results open a wide range of possibilities for using magnetic nanoparticles in general plant research and agronomy. The nanoparticles can be charged with different substances, introduced within the plants and, if necessary, concentrated into localized areas by using magnets. Also simple or more complex microscopical techniques can be used in localization studies.

Gonzalez-Melendi, P.; Fernandez-Pacheco, R.; Coronado, M. J.; Corredor, E.; Testillano, P. S.; Risueno, M. C.; Marquina, C.; Ibarra, M. R.; Rubiales, D.; Perez-de-Luque, A.

2008-01-01

343

Nanoparticles of 2-deoxy-d-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment.  

PubMed

Based on the facilitative glucose transporter (GLUT) over-expression on both blood-brain barrier (BBB) and glioma cells, 2-deoxy-d-glucose modified poly(ethylene glycol)-co-poly(trimethylene carbonate) nanoparticles (dGlu-NP) were developed as a potential dual-targeted drug delivery system for enhancing the BBB penetration via GLUT-mediated transcytosis and improving the drug accumulation in the glioma via GLUT-mediated endocytosis. In vitro physicochemical characterization of the dual-targeted nanoparticulate system presented satisfactory size of 71 nm with uniform distribution, high encapsulation efficiency and adequate loading capacity of paclitaxel (PTX). Compared with non-glucosylated nanoparticles (NP), a significantly higher amount of dGlu-NP was internalized by RG-2 glioma cells through caveolae-mediated and clathrin-mediated endocytosis. Both of the transport ratios across the in vitro BBB model and the cytotoxicity of RG-2 cells after crossing the BBB were significantly greater of dGlu-NP/PTX than that of NP/PTX. In vivo fluorescent image indicated that dGlu-NP had high specificity and efficiency in intracranial tumor accumulation. The anti-glioblastoma efficacy of dGlu-NP/PTX was significantly enhanced in comparison with that of Taxol and NP/PTX. Preliminary safety tests showed no acute toxicity to hematological system, liver, kidney, heart, lung and spleen in mice after intravenous administration at a dose of 100 mg/kg blank dGlu-NP per day for a week. Therefore, these results indicated that dGlu-NP developed in this study could be a potential dual-targeted vehicle for brain glioma therapy. PMID:24125772

Jiang, Xinyi; Xin, Hongliang; Ren, Qiuyue; Gu, Jijin; Zhu, Lingjun; Du, Fengyi; Feng, Chunlai; Xie, Yike; Sha, Xianyi; Fang, Xiaoling

2013-10-11

344

Recovering Delivery for Digital Rhetoric  

Microsoft Academic Search

This article develops a rhetorical theory of delivery for Internet-based communications. Delivery, one of the five key canons of classical rhetoric, is still an important topic for rhetorical analysis and production. However, delivery needs to be re-theorized for the digital age. In Part 1, the article notes the importance of delivery in traditional rhetoric and argues that delivery should be

James E. Porter

2009-01-01

345

Colon Targeted Drug Delivery Systems: A Review on Primary and Novel Approaches  

Microsoft Academic Search

The colon is a site where both local and systemic delivery of drugs can take place. Local delivery allows topical treatment of inflammatory bowel disease. However, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reducing the systemic side effects. This review, mainly compares the primary approaches for CDDS (Colon Specific Drug Delivery)

Anil K. Philip; Betty Philip

2010-01-01

346

Importance of novel drug delivery systems in herbal medicines  

PubMed Central

Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems. However, modern phytopharmaceutical research can solve the scientific needs (such as determination of pharmacokinetics, mechanism of action, site of action, accurate dose required etc.) of herbal medicines to be incorporated in novel drug delivery system, such as nanoparticles, microemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on. This article summarizes various drug delivery technologies, which can be used for herbal actives together with some examples.

Devi, V. Kusum; Jain, Nimisha; Valli, Kusum S.

2010-01-01

347

Polymeric vectors for ocular gene delivery  

PubMed Central

Gene therapy holds promise for the treatment of many inherited and acquired diseases of the eye. Successful ocular to targeted cells with minimal toxicity. A major gene therapy interventions depend on challenge is to overcome both intracellular and extracellular barriers associated with ocular gene delivery. Numerous viral and nonviral vectors were explored to improve transfection efficiency. Among nonviral delivery systems, polymeric vectors have gained significant attention in recent years owing to their nontoxic and non-immunogenic nature. Polyplexes or nanoparticles can be prepared by interaction of cationic polymers with DNA, which facilitate cellular uptake, endolysosomal escape and nuclear entry through active mechanisms. Chemical modification of these polymers allows for the generation of flexible delivery vectors with desirable properties. In this article several synthetic and natural polymeric systems utilized for ocular gene delivery are discussed.

Tamboli, Viral; Mishra, Gyan P; Mitra, Ashim K

2011-01-01

348

Intermittent preventive treatment of malaria in pregnancy: Evaluation of a new delivery approach and the policy implications for malaria control in Uganda  

Microsoft Academic Search

The impact of intermittent preventive treatment (IPT) on malaria in pregnancy is well known. In countries where this policy is implemented, poor access and low compliance to this intervention has been widely reported. A study was designed to assess a new approach to deliver IPT to pregnant women through traditional birth attendants (TBAs), drug-shop vendors (DSVs), community reproductive health workers

Anthony K. Mbonye; Ib Bygbjerg; Pascal Magnussen

2007-01-01

349

Comparing Two Service Delivery Models for Homeless Individuals With Complex Behavioral Health Needs: Preliminary Data From Two SAMHSA Treatment for Homeless Studies  

Microsoft Academic Search

Assertive Community Treatment (ACT) and the Comprehensive, Continuous, Integrated System of Care (CCISC) are two models for delivering services to homeless persons with complex behavioral health needs. This quasi-experimental study presents preliminary data comparing these two programs. The first program was based out of a community mental health center and utilized the ACT model of care with supported housing (ACT-SH),

M. Scott Young; Colleen Clark; Kathleen Moore; Blake Barrett

2009-01-01

350

[The moon and delivery].  

PubMed

In different cultures and mythologies, the moon is related with fertility, pregnancy and delivery. Professional obstetricians also notice an increase in care demands on the days when the moon is full. Many studies have been made which try to correlate delivery processes to the phases of the moon with contradictory results. The authors plan to try to find any basis in fact which support these popular beliefs and to discover if lunar phases bear an influence on the distribution of deliveries. They carried out a descriptive transversal study on a total of 1715 unassisted deliveries over the course of ten complete lunar cycles. The authors have carried out a descriptive and inferential analysis, a one way ANOVA and a Kruskal Wallis test on their three data bases which are general, primipara and multipara in which they contemplated the total number of deliveries per phase, the mean of each phase, as well as the central day in each phase of the lunar cycle. The differences found in the distribution of deliveries over the four lunar phases, along with the comparison of the means and the comparison of the number of deliveries on the central day in each phase are not statistically significant. The different phases in the lunar cycle and especially the full moon do not appear to have any influence over the distribution of deliveries in this study. PMID:15648892

Romero Martínez, Jorge; Guerrero Guijo, Inmaculada; Artura Serrano, Antonio

2004-11-01

351

A generalized a priori dose uncertainty model of IMRT delivery  

SciTech Connect

Multileaf collimator-based intensity modulated radiation therapy (IMRT) is complex because each intensity modulated field consists of hundreds of subfields, each of which is associated with an intricate interplay of uncertainties. In this study, the authors have revised the previously introduced uncertainty model to provide an a priori accurate prediction of dose uncertainty during treatment planning in IMRT. In the previous model, the dose uncertainties were categorized into space-oriented dose uncertainty (SOU) and nonspace-oriented dose uncertainty (NOU). The revised model further divided the uncertainty sources into planning and delivery. SOU and NOU associated with a planning system were defined as inherent dose uncertainty. A convolution method with seven degrees of freedom was also newly applied to generalize the model for practical clinical cases. The model parameters were quantified through a set of measurements, accumulated routine quality assurance (QA) data, and peer-reviewed publications. The predicted uncertainty maps were compared with dose difference distributions between computations and 108 simple open-field measurements using a two-dimensional diode array detector to verify the validity of the model parameters and robustness of the generalized model. To examine the applicability of the model to overall dose uncertainty prediction in IMRT, a retrospective analysis of QA measurements using the diode array detector for 32 clinical IM fields was also performed. A scatter diagram and a correlation coefficient were employed to investigate a correlation of the predicted dose uncertainty distribution with the dose discrepancy distribution between calculation and delivery. In addition, a {gamma} test was performed to correlate failed regions in dose verification with the dose uncertainty map. The quantified model parameters well correlated the predicted dose uncertainty with the probable dose difference between calculations and measurements. It was visually validated with the scatter diagrams. The average correlation coefficient between uncertainty and dose difference of 108 verification measurements was 0.80{+-}0.04, indicating a strong linear correlation. In the clinical IM field studies, the dose uncertainty map mimicked the probable dose difference distribution. The average correlation coefficient between the overall dose uncertainty and the dose difference of 32 QA measurements (total 13 184 comparison points) was 0.75{+-}0.07, which also indicated a strong linear correlation between them. The failed regions of the {gamma} test remarkably corresponded to relatively high dose uncertainty. In conclusion, the dose uncertainty map was able to highlight high dose uncertainty regions, where more care should be taken during the treatment plan. The a priori accurate prediction of dose uncertainty in IMRT will significantly improve the treatment plan evaluation process, thus improving the quality of radiation treatments.

Jin, Hosang; Palta, Jatinder; Suh, Tae-Suk; Kim, Siyong [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, Florida 32611 (United States); Department of Radiation Oncology, University of Florida, Gainesville, Florida 32610 (United States); Department of Biomedical Engineering, Catholic Medical University, Seoul (Korea, Republic of); Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida 32224 (United States)

2008-03-15

352

Convection-enhanced intraparenchymal delivery (CEID) of cytosine arabinoside (AraC) for the treatment of HIV-related progressive multifocal leukoencephalopathy (PML)  

Microsoft Academic Search

AIDS-related PML continues to be a relatively common and rapidly fatal infection in patients with AIDS, and no effective therapy\\u000a has been established to alleviate the effects of this disease. Through the years, isolated reports and small case studies\\u000a have shown somewhat encouraging results using cytosine arabinoside (AraC) in the treatment of PML. The optimism behind the\\u000a use AraC for

Robert M. Levy; Eugene Major; Mir Jafer Ali; Bruce Cohen; Dennis Groothius

2001-01-01

353

Intermittent preventive treatment of malaria in pregnancy: a new delivery system and its effect on maternal health and pregnancy outcomes in Uganda  

Microsoft Academic Search

Objective To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. Methods A non-randomized community trial was implemented in 21 community clusters (intervention) and four clusters where health units provided routine IPTp (control). The primary outcome measures were access and adherence to

A K Mbonye; I C Bygbjerg; P Magnussen

354

Separating therapeutic efficacy from glucocorticoid side-effects in rodent arthritis using novel, liposomal delivery of dexamethasone phosphate: long-term suppression of arthritis facilitates interval treatment  

Microsoft Academic Search

INTRODUCTION: Glucocorticoids have extensively been used in the treatment of rheumatoid arthritis and other inflammatory diseases. However, their side-effects remain the major limitation in clinical use and an improved therapeutic index is needed. METHODS: Therapeutic efficacy and persistence of free and liposomal dexamethasone phosphate (DXM-P) were determined in mouse collagen-induced arthritis. For regimens with equal therapeutic benefit, the side-effect profiles

Una Rauchhaus; Franz Werner Schwaiger; Steffen Panzner

2009-01-01

355

Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.  

PubMed

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing. PMID:18338834

Hüttinger, Cornelia; Hirschberger, Johannes; Jahnke, Anika; Köstlin, Roberto; Brill, Thomas; Plank, Christian; Küchenhoff, Helmut; Krieger, Stefan; Schillinger, Ulrike

2008-06-01

356

Development of a Microfluidics-Based Intracochlear Drug Delivery Device  

Microsoft Academic Search

Background: Direct delivery of drugs and other agents into the inner ear will be important for many emerging therapies, including the treatment of degenerative disorders and guiding regeneration. Methods: We have taken a microfluidics\\/MEMS (MicroElectroMechanical Systems) technology approach to develop a fully implantable reciprocating inner-ear drug-delivery system capable of timed and sequenced delivery of agents directly into perilymph of the

William F. Sewell; Jeffrey T. Borenstein; Zhiqiang Chen; Jason Fiering; Ophir Handzel; Maria Holmboe; Ernest S. Kim; Sharon G. Kujawa; Michael J. McKenna; Mark M. Mescher; Brian Murphy; Erin E. Leary Swan; Marcello Peppi; Sarah Tao

2009-01-01

357

Proton treatment room concepts for precision and efficiency.  

PubMed

Proton radiation therapy involves accurate delivery of proton beams to targets inside the body without direct visual control of the internal anatomy. Targeting of the tumor and avoidance of critical structures within the patient have to be both accurate and precise to achieve the desired therapeutic results. Good understanding of proton radiation delivery and patient alignment concepts in the treatment room is essential to achieve this goal. This overview article presents treatment room concepts that will ensure precise proton beam delivery and, at the same time, guarantee an efficient patient throughput. Concepts discussed include effective patient immobilization, image-guided alignment verification, appropriate training of radiotherapists, and the physician's integrative role in understanding the complex spatial relationships between tumor, organs at risk, treatment beam configuration, and application of proton radiation dose. It will be demonstrated that in addition to the technical armamentarium, now commonplace in modern radiation oncology departments, the interaction between radiation oncologist, medical physicist and radiotherapist is important for efficient operation of a proton treatment facility. PMID:17668953

Schulte, Reinhard W

2007-08-01

358

MODIFICATION AND CHARACTERIZATION OF DRY MATERIAL FEEDER FOR DELIVERY OF RED AND VIOLET DYE MIXTURES  

EPA Science Inventory

Uniform delivery of dry material for stable concentrations of aerosols in inhalation exposure chambers is essential in inhalation experiments. his paper characterizes an AccuRate dry material feeder with modifications, for different helix sizes, actuation rates, nozzle types and ...

359

Novel gene delivery systems  

PubMed Central

Gene therapy is an emerging field in medical and pharmaceutical sciences because of its potential in treating chronic diseases like cancer, viral infections, myocardial infarctions, and genetic disorders. Application of gene therapy is limited because of lack of suitable methods for proper introduction of genes into cells and therefore, this is an area of interest for most of the researchers. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors. Several nonviral and viral gene transfer methods have been developed. Even though the viral agents have a high transferring efficiency, they are difficult to handle due to their toxicity. To overcome the safety problems of the viral counterpart, several nonviral in vitro and in vivo gene delivery systems are developed. Out of these, the most promising and latest systems include polymer-based nonviral gene carriers, dendrimers, and physical means like electroporation, microinjection, etc., Shunning of possible immunogenicity and toxicity, and the feasibility of repeated administration are some of the merits of nonviral gene delivery systems over viral gene delivery. An ideal nonviral gene carrying system should possess all these merits without any compromise to its gene transferring efficiency. The viral gene delivery systems include lytic and nonlytic vectors for drug delivery. Inspite of its toxicity they are still preferred because of their long term expression, stability, and integrity. This review explores the recent developments and relevancy of the novel gene delivery systems in gene therapy.

Manjila, Steffy B; Baby, Jomon N; Bijin, Elambilan N; Constantine, Icey; Pramod, Kannissery; Valsalakumari, Janardhanan

2013-01-01

360

Delivery quality assurance with ArcCHECK.  

PubMed

Radiation therapy requires delivery quality assurance (DQA) to ensure that treatment is accurate and closely follows the plan. We report our experience with the ArcCHECK phantom and investigate its potential optimization for the DQA process. One-hundred seventy DQA plans from 84 patients were studied. Plans were classified into 2 groups: those with the target situated on the diodes of the ArcCHECK (D plans) and those with the target situated at the center (C plans). Gamma pass rates for 8 target sites were examined. The parameters used to analyze the data included 3%/3 mm with the Van Dyk percent difference criteria (VD) on, 3%/3 mm with the VD off, 2%/2 mm with the VD on, and x/3 mm with the VD on and the percentage dosimetric agreement "x" for diode plans adjusted. D plans typically displayed maximum planned dose (MPD) on the cylindrical surface containing ArcCHECK diodes than center plans, resulting in inflated gamma pass rates. When this was taken into account by adjusting the percentage dosimetric agreement, C plans outperformed D plans by an average of 3.5%. ArcCHECK can streamline the DQA process, consuming less time and resources than radiographic films. It is unnecessary to generate 2 DQA plans for each patient; a single center plan will suffice. Six of 8 target sites consistently displayed pass rates well within our acceptance criteria; the lesser performance of head and neck and spinal sites can be attributed to marginally lower doses and increased high gradient of plans. PMID:22917964

Neilson, Christopher; Klein, Michael; Barnett, Rob; Yartsev, Slav

2012-08-21

361

Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues  

PubMed Central

Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair.

Nichols, Scott P.; Storm, Wesley L.; Koh, Ahyeon; Schoenfisch, Mark H.

2012-01-01

362

Machine learning algorithms for accurate flow-based network traffic classification: Evaluation and comparison  

Microsoft Academic Search

The task of network management and monitoring relies on an accurate characterization of network traffic generated by different applications and network protocols. We employ three supervised machine learning (ML) algorithms, Bayesian Networks, Decision Trees and Multilayer Perceptrons for the flow-based classification of six different types of Internet traffic including peer-to-peer (P2P) and content delivery (Akamai) traffic. The dependency of the

Murat Soysal; Ece Guran Schmidt

2010-01-01

363

Vacuum-assisted delivery.  

PubMed

The literature seems to allow certain general conclusions regarding the choice of instrument for assisted vaginal delivery. Both forceps and vacuum extraction offer certain advantages and drawbacks. Forceps are more difficult to apply, more prone to potentially significant facial injuries, require generally better maternal analgesia, and are associated with increased maternal soft tissue trauma. Vacuum extractors in general are easier to apply, are more likely to result in scalp trauma, and may be associated with increased rates of intracranial trauma. It seems likely that factors particular to each patient may play a significant role in the genesis of delivery associated with maternal and neonatal morbidity. Because of the ease of application, vacuum extractors may be used potentially in circumstances in which forceps assistance would not be attempted, allowing an operator of average experience to perform rotational deliveries. The use of vacuum extraction does appear to decrease the incidence of cesarean section in delivery populations. Given the apparent association between difficult assisted deliveries and increased neonatal morbidity, it is incumbent on the operator to attempt delivery only when vaginal delivery seems to be a safe option. Furthermore, the operator in such circumstances must be willing to reassess the attempt if initial attempts are not met with success. The minimal rates of significant intracranial injury associated with vacuum extraction in randomized studies of the method demonstrate the relative safety of the vacuum extraction when used judiciously. The ultimate choice of the route of delivery and method of assisted delivery should reflect a consideration of the fetal station, presentation, and maternal and fetal circumstances. It is hoped that further investigations in this area may clarify some of the issues discussed in this article. PMID:8665766

Williams, M C

1995-12-01

364

Quantification of horseradish peroxidase delivery into the arterial wall in vivo as a model of local drug treatment: Comparison between a porous and a gel-coated balloon catheter  

Microsoft Academic Search

Purpose: To quantify horseradish peroxidase (HRP) delivery into the arterial wall, as a model of local drug delivery, and to compare\\u000a two different percutaneous delivery balloons.\\u000a \\u000a \\u000a Methods: Perforated and hydrophilic hydrogel-coated balloon catheters were used to deliver HRP in aqueous solution into the wall of\\u000a porcine iliac arteries in vivo. HRP solutions of 1 mg\\/ml were used together with both

Armin Dick; Wolfgang Kromen; Eberhard Jüngling; Stephanie Grosskortenhaus; Helmut Kammerrmeier; Dierk Vorwerk; Rolf W. Günther

1999-01-01

365

UC Davis researchers refine nanoparticles for more accurate delivery of cancer drugs:  

Cancer.gov

A new class of nanoparticles, synthesized by a UC Davis research team to prevent premature drug release, holds promise for greater accuracy and effectiveness in delivering cancer drugs to tumors. The work is published in the current issue of Angewandte Chemie, a leading international chemistry journal.

366

Accurate delivery of single biomolecules by polyethylene glycol coated submicrometer pipettes  

NASA Astrophysics Data System (ADS)

There is a great interest to quantitatively manipulate, separate, and deliver low concentrations or even single biomolecules in submicrometer-sized channels. We report the use of cross-linked four-star polyethylene glycol (PEG) as a new coating technique for microchannels. PEG-coating efficiently reduces the electroosmotic flow (EOF) and non-specific adsorption to the glass walls. Our results demonstrate that individual fluorescently labeled hydrophobic cell adhesion proteins (fibronectin molecules) can be drawn through PEG-coated submicrometer pipettes in aqueous solution by electrokinetic forces without the addition of detergents or other additives which potentially deteriorate the activity and specificity of biomolecules.

Park, Chong-Woo; Knemeyer, Jens-Peter; Marmé, Nicole; Möller, Martin; Spatz, Joachim; Wolfrum, Jürgen; Sauer, Markus

2004-05-01

367

Treatment  

Microsoft Academic Search

Few clinical issues have been more hotly contested than the treatment of ADHD, particularly the relative value of medication\\u000a versus behavioral\\/psychosocial treatments (DuPaul & Power, 2008; Toplak, Connors, Shuster, Knezevic, & Parks, 2008; Wauschbusch\\u000a & Hill, 2003). Treatment decisions are often complicated by biases reflecting media coverage of diagnostic and treatment controversies,\\u000a cultural background, previous experiences or anecdotal stories from

Stephen E. Brock; Shane R. Jimerson; Robin L. Hansen

368

The formulation and delivery of curcumin with solid lipid nanoparticles for the treatment of on non-small cell lung cancer both in vitro and in vivo.  

PubMed

Curcumin was determined to have anticancer potency on several kinds of carcinoma. However, its medical application was limited because of its poor bioavailability, unsatisfying dispersity and rapid metabolism in vivo. In this study, curcumin was delivered by solid lipid nanoparticles (SLN) for lung cancer treatment. The physiochemical characters of SLN-curcumin were detected by HPLC, TEM, Zeta potential analysis and FTIR, and the anticancer efficiency on lung cancer was determined both in vitro and in vivo. SLN-curcumin was synthesized by sol-gel method with the size ranged from 20 to 80nm. After being loaded in SLN, the IC50 of SLN-curcumin on A549 cells was 4?M, only 1/20 of plain drug. The plasmid concentration of curcumin was highly increased in mice via i.p. after loaded with SLN. Furthermore, SLN-curcumin enhanced the targeting of curcumin to lung and tumor, which finally increased the inhibition efficiency of curcumin from 19.5% to 69.3%. The Flow Cytometry (FCM) analysis and immuno staining confirmed that the inhibition effect mostly came from apoptosis, but not necrosis. The tumor targeting and profound tumor inhibition effect of SLN-curcumin indicated its medical application on lung cancer treatment, and also provided a novel method for new anticancer agents' development. PMID:24094190

Wang, Ping; Zhang, Libin; Peng, Hao; Li, Yongwu; Xiong, Jian; Xu, Zheyuan

2013-08-14

369

Microsponge delivery system.  

PubMed

Microsponges are polymeric delivery systems consisting of porous microspheres having a size range in between 5 to 300 microm depending upon the degree of smoothness or after feel required for the end formulations. Microsponge Delivery System MDS is a unique technology for controlled delivery of drug. The present review introduces Microsponge technology along with its synthesis, characterization, programmable parameters and release mechanism of MDS. Wide ranges of applications are also suggested to develop drug or cosmetic products with enhanced safety and efficacy. MDS can provide increased efficacy for topically active agents with enhanced safety, extended product stability and improved aesthetic properties in an efficient and novel manner. PMID:17456031

Chadawar, Vikrant; Shaji, Jessy

2007-04-01

370

Persistent Expression of FLAG-tagged Micro dystrophin in Nonhuman Primates Following Intramuscular and Vascular Delivery  

Microsoft Academic Search

Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct

Louise R Rodino-Klapac; Chrystal L Montgomery; William G Bremer; Kimberly M Shontz; Vinod Malik; Nancy Davis; Spencer Sprinkle; Katherine J Campbell; Zarife Sahenk; K Reed Clark; Christopher M Walker; Jerry R Mendell; Louis G Chicoine

2010-01-01

371

Clinical effect of continuous corrective force delivery in the non-operative treatment of idiopathic scoliosis: a prospective cohort study of the triac-brace  

PubMed Central

A prospective cohort study of skeletally immature idiopathic scoliotic patients treated with the TriaC brace. To determine if the TriaC brace is effective in preventing curve progression in immature adolescent idiopathic scoliotic patients with a very high risk of curve progression based on reported natural history data. The aim of the newly introduced TriaC brace is to reverse the pathologic transverse force pattern by externally applied and continuously present orthotic forces. In the frontal plane the force system used in the TriaC brace is similar to the force system of the conventional braces. However, in the sagittal plane the force system acts only on the thoracic region. In addition, the brace allows upper trunk flexibility without affecting the corrective forces during body motion. In a preliminary study it is demonstrated that the brace prevents further progression of both the Cobb angle and axial rotation in idiopathic scoliosis. Skeletally immature patients with idiopathic scoliosis with curves between 20 and 40° were studied prospectively. Skeletally immature was defined as a Risser sign 0 or 1 for both boys and girls, or pre-menarche or less than 1-year post-menarche for girls. Curves of less than 30° had to have documented progression before entry. The mean age of the patients at the start of treatment was 11.3 ± 3.1 years. All measurements were collected by a single observer, and all patients were followed up to skeletal maturity. Treatment was complete for all participants when they had reached Risser sign 4 and did not show any further growth at length measurements. This was at a mean age of 15.6 ± 1.1 years, with a mean follow-up of 1.6 years post bracing. In our study a successful outcome was obtained in 76% of patients treated with the TriaC brace. Comparing our data to literature data on natural history of a similar cohort shows that the TriaC brace significantly alters the predicted natural history. The current study demonstrates that treatment with the TriaC brace reduces the scoliosis, and that the achieved correction is maintained in some degree after skeletal maturity is reached and bracing is discontinued. It also prevents further progression of the Cobb angle in idiopathic scoliosis. The new brace does not differ from the conventional braces as far as maintaining the deformity is concerned.

Veldhuizen, Albert G.; Nijenbanning, Gert

2007-01-01

372

Clinical effect of continuous corrective force delivery in the non-operative treatment of idiopathic scoliosis: a prospective cohort study of the TriaC-brace.  

PubMed

A prospective cohort study of skeletally immature idiopathic scoliotic patients treated with the TriaC brace. To determine if the TriaC brace is effective in preventing curve progression in immature adolescent idiopathic scoliotic patients with a very high risk of curve progression based on reported natural history data. The aim of the newly introduced TriaC brace is to reverse the pathologic transverse force pattern by externally applied and continuously present orthotic forces. In the frontal plane the force system used in the TriaC brace is similar to the force system of the conventional braces. However, in the sagittal plane the force system acts only on the thoracic region. In addition, the brace allows upper trunk flexibility without affecting the corrective forces during body motion. In a preliminary study it is demonstrated that the brace prevents further progression of both the Cobb angle and axial rotation in idiopathic scoliosis. Skeletally immature patients with idiopathic scoliosis with curves between 20 and 40 degrees were studied prospectively. Skeletally immature was defined as a Risser sign 0 or 1 for both boys and girls, or pre-menarche or less than 1-year post-menarche for girls. Curves of less than 30 degrees had to have documented progression before entry. The mean age of the patients at the start of treatment was 11.3 +/- 3.1 years. All measurements were collected by a single observer, and all patients were followed up to skeletal maturity. Treatment was complete for all participants when they had reached Risser sign 4 and did not show any further growth at length measurements. This was at a mean age of 15.6 +/- 1.1 years, with a mean follow-up of 1.6 years post bracing. In our study a successful outcome was obtained in 76% of patients treated with the TriaC brace. Comparing our data to literature data on natural history of a similar cohort shows that the TriaC brace significantly alters the predicted natural history. The current study demonstrates that treatment with the TriaC brace reduces the scoliosis, and that the achieved correction is maintained in some degree after skeletal maturity is reached and bracing is discontinued. It also prevents further progression of the Cobb angle in idiopathic scoliosis. The new brace does not differ from the conventional braces as far as maintaining the deformity is concerned. PMID:17926071

Bulthuis, Gerben J; Veldhuizen, Albert G; Nijenbanning, Gert

2007-10-10

373

Drug delivery to the Lungs 21.  

PubMed

Drug Delivery to the Lungs 21 was focused exclusively on delivery technologies of medicines for the treatment of diseases that are 'local' to the respiratory tract or for wider 'systemic' distribution. Therefore, the range of diseases that can be treated via delivering drugs to the lungs is large and diverse. This diversity means that the delivery technologies (device and/or formulation) are also very varied. Moreover, the patient is critically involved when using drug-delivery technologies to the lungs as their inhalation and 'user' characteristics are pivotal in ensuring that the correct dose is given and reaches the appropriate part of the respiratory tract. Thus, Drug Delivery to the Lungs 21 was a wide-ranging conference, ideal for an overview of current and future inhaled-delivery technologies. The conference was split into various themed sections and supported by approximately 65 posters. Furthermore, the conference was preceded by a workshop organized by the European Pharmaceutical Aerosol Group on abbreviated impactor measurement, which is a tool currently of much interest in assessing aerosol products (see separate summary). The conference initiated a number of innovations this year, including a Facebook page on which delegates and organizers could follow and 'chat' about conference proceedings. PMID:22834000

Mitchell, Jolyon P; Nichols, Steve C

2011-03-01

374

Non-invasive photonics-based diagnostic imaging, monitoring, and light delivery techniques for the recognition, quantification, and treatment of malignant and chronic inflammatory conditions  

NASA Astrophysics Data System (ADS)

We report firsthand on innovative developments in non-invasive, biophotonic techniques for a wide range of diagnostic, imaging and treatment options, including the recognition and quantification of cancerous, pre-cancerous cells and chronic inflammatory conditions. These techniques have benefited from the ability to target the affected site by both monochromatic light and broad multiple wavelength spectra. The employment of such wavelength or color-specific properties embraces the fluorescence stimulation of various photosensitizing drugs, and the instigation and detection of identified fluorescence signatures attendant upon laser induced fluorescence (LIF) phenomena as transmitted and propagated by precancerous, cancerous and normal tissue. In terms of tumor imaging and therapeutic and treatment options, we have exploited the abilities of various wavelengths to penetrate to different depths, through different types of tissues, and have explored quantifiable absorption and reflection characteristics upon which diagnostic assumptions can be reliably based and formulated. These biophotonic-based diagnostic, sensing and imaging techniques have also benefited from, and have been further enhanced by, the integrated ability to provide various power levels to be employed at various stages in the procedure. Applications are myriad, including non-invasive, non destructive diagnosis of in vivo cell characteristics and functions; light-based tissue analysis; real-time monitoring and mapping of brain function and of tumor growth; real time monitoring of the surgical completeness of tumor removal during laser-imaged/guided brain resection; diagnostic procedures based on fluorescence life-time monitoring, the monitoring of chronic inflammatory conditions (including rheumatoid arthritis), and continuous blood glucose monitoring in the control of diabetes.

Davies, N.; Davies-Shaw, D.; Shaw, J. D.

2007-03-01

375

Application of Sterylglucoside-Containing Particles for Drug Delivery  

Microsoft Academic Search

Recent advances in biotechnology have promoted biomolecular targeting of drugs, peptides and genes in the treatment and management of major diseases and infections. Therapeutic development of drugs and delivery systems may have various objectives: Systemic drugs require optimal delivery and uptake at target sites; peptide drugs require alternative routes of administration, such as nasal or intestinal absorption; gene medicines need

Yoshie Maitani; Koji Nakamura; Kumi Kawano

376

Current status and future potential of transdermal drug delivery  

Microsoft Academic Search

The past twenty five years have seen an explosion in the creation and discovery of new medicinal agents. Related innovations in drug delivery systems have not only enabled the successful implementation of many of these novel pharmaceuticals, but have also permitted the development of new medical treatments with existing drugs. The creation of transdermal delivery systems has been one of

Mark R. Prausnitz; Samir Mitragotri; Robert Langer

2004-01-01

377

Tripartite complex for axonal transport drug delivery achieves pharmacological effect  

Microsoft Academic Search

BACKGROUND: Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy

Aaron G Filler; Garth T Whiteside; Mark Bacon; Martyn Frederickson; Franklyn A Howe; Miri D Rabinowitz; Alan J Sokoloff; Terrence W Deacon; Chris Abell; Raj Munglani; John R Griffiths; B Anthony Bell; Andrew ML Lever

2010-01-01

378

Local Delivery of Tobramycin from Injectable Biodegradable Polyurethane Scaffolds  

Microsoft Academic Search

Infections often compromise the healing of open fractures. While local antibiotic delivery from PMMA beads is an established clinical treatment of infected fractures, surgical removal of the beads is required before implanting a bone graft. A more ideal therapy would comprise a scaffold and antibiotic delivery system administered in one procedure. Biodegradable polyurethane (PUR) scaffolds have been shown in previous

Andrea E. Hafeman; Katarzyna J. Zienkiewicz; Erin Carney; Brandon Litzner; Charles Stratton; Joseph C. Wenke; Scott A. Guelcher

2010-01-01

379

Micro- and nano-fabricated implantable drug-delivery systems  

PubMed Central

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentrations over entire treatment durations in order to optimize drug action. This article focuses on new drug administration modalities achieved using implantable drug-delivery systems that are enabled by micro- and nano-fabrication technologies, and microfluidics. Recent advances in drug administration technologies are discussed and remaining challenges are highlighted.

Meng, Ellis; Hoang, Tuan

2013-01-01

380

Review article IMRT: delivery techniques and quality assurance  

Microsoft Academic Search

Intensity modulated radiotherapy (IMRT) is a major development in the delivery of radiation therapy that has the potential to improve patient outcome by reducing morbidity or increasing local tumour control. Delivery techniques include those based on purpose built devices and treatment machines together with those utilizing the capabilities of computer controlled multileaf collimators which are more widely available. The complexity

P C WILLIAMS

2003-01-01

381

Educational Telecommunications Delivery Systems.  

National Technical Information Service (NTIS)

This monograph is a single volume reference manual providing an overall review of the current status and likely near future application of six major educational telecommunications delivery technologies. The introduction provides an overview to the usage a...

J. A. Curtis J. M. Biedenbach

1979-01-01

382

Implantable Insulin Delivery System.  

National Technical Information Service (NTIS)

An insulin delivery system suitable for experimental implants and external use has been developed to study glucose control for diabetics. The programmable system developed at Sandia National Laboratories, in conjunction with the University of New Mexico S...

J. T. Love J. I. Gaona

1981-01-01

383

Project Delivery Methods.  

ERIC Educational Resources Information Center

|Describes project delivery methods that are replacing the traditional Design/Bid/Build linear approach to the management, design, and construction of new facilities. These variations can enhance construction management and teamwork. (SLD)|

Dolan, Thomas G.

2003-01-01

384

Integrated Service Delivery Report.  

National Technical Information Service (NTIS)

A demonstration project undertaken by the State of Washington Department of Social and Health Services to determine the value of integrated service delivery systems in terms of the appropriateness, accessibility, effectiveness, and cost of services is doc...

1975-01-01

385

Customised birthweight standards accurately predict perinatal morbidity  

PubMed Central

Objective Fetal growth restriction is associated with adverse perinatal outcome but is often not recognised antenatally, and low birthweight centiles based on population norms are used as a proxy instead. This study compared the association between neonatal morbidity and fetal growth status at birth as determined by customised birthweight centiles and currently used centiles based on population standards. Design Retrospective cohort study. Setting Referral hospital, Barcelona, Spain. Patients A cohort of 13?661 non?malformed singleton deliveries. Interventions Both population?based and customised standards for birth weight were applied to the study cohort. Customised weight centiles were calculated by adjusting for maternal height, booking weight, parity, ethnic origin, gestational age at delivery and fetal sex. Main outcome measures Newborn morbidity and perinatal death. Results The association between smallness for gestational age (SGA) and perinatal morbidity was stronger when birthweight limits were customised, and resulted in an additional 4.1% (n?=?565) neonates being classified as SGA. Compared with non?SGA neonates, this newly identified group had an increased risk of perinatal mortality (OR 3.2; 95% CI 1.6 to 6.2), neurological morbidity (OR 3.2; 95% CI 1.7 to 6.1) and non?neurological morbidity (OR 8; 95% CI 4.8 to 13.6). Conclusion Customised standards improve the prediction of adverse neonatal outcome. The association between SGA and adverse outcome is independent of the gestational age at delivery.

Figueras, Francesc; Figueras, Josep; Meler, Eva; Eixarch, Elisenda; Coll, Oriol; Gratacos, Eduard; Gardosi, Jason; Carbonell, Xavier

2007-01-01

386

Evaluating water delivery in tertiary units Part l: Method  

Microsoft Academic Search

In most irrigated areas, the present desire for rehabilitation raises the need for an accurate analysis of the actual situation. We present a new method to evaluate the quality of water delivery and the origin of water deficits (and irrigation water losses) in an irrigated area, based on the simultaneous analysis of distribution rules and actual irrigation events. First, a

Luc Gilot

1997-01-01

387

In situ delivery of cytokines by genetically engineered Lactococcus lactis  

Microsoft Academic Search

The development of novel approaches that allow for accurate targeting of therapeutics to the bowel mucosa is a priority in the research on inflammatory bowel disease. We have engineered Lactococcus lactis to secrete soluble, fully active, correctly processed cytokines. We have used these live, recombinant strains for the in situ delivery of mouse interleukin (mIL)-2, -6 and -10 at airway

Lothar Steidler

2002-01-01

388

Accurate force measurement using optical interferometer  

NASA Astrophysics Data System (ADS)

The present status and the future prospects of a method for accurate force measurement, the levitation mass method (LMM), is reviewed. The LMM has been proposed and improved by the authors. In the LMM, the inertial force of a mass levitated using an aero-static linear bearing is used as the reference/known force applied to the objects under test, such as force transducers, materials or structures. The inertial force of the levitated mass is measured using an optical interferometer. Since the force is one of the most major physical quantities, the application of the LMM as the most accurate dynamic force measurement method is very wide.

Fujii, Yusaku

2012-06-01

389

Bacterial delivery system  

US Patent & Trademark Office Database

We describe a bacterial delivery system for the delivery of DNA and antigens into cells. We constructed an attenuated bacterial vector which enters mammalian cells and ruptures delivering functional plasmid DNA and antigens into the cell cytoplasm. This Shigella vector was designed to deliver DNA to colonic surfaces, thus opening the possibility of oral and other mucosal DNA immunization and gene therapy strategies. The attenuated Shigella is also useful as a vaccine for reducing disease symptoms caused by Shigella.

Branstrom; Arthur A. (Rockville, MD); Sizemore; Donata R. (Gaithersburg, MD); Sadoff; Jerald C. (Washington, DC)

2006-05-16

390

Nanoparticles for Pulmonary Delivery  

Microsoft Academic Search

\\u000a This chapter aims to provide a rational for the use of nanoparticles in pulmonary delivery as well as an overview of strategies\\u000a and physiological implications of nanoparticle delivery to the lungs. Formulation aspects of nanoparticle systems in the form\\u000a of liquid dispersions and inhaled dry powders are also reviewed. The chapter also addresses the expanse of lung toxicology\\u000a research surrounding

Alan B. Watts; Robert O. Williams

391

Vacuum actuated gas delivery  

Microsoft Academic Search

The new Vacuum Actuated Cylinder (VACTM) gas source provides sub-atmospheric pressure delivery of the metal fluorides commonly used as dopants for ion implant. The VAC gas source is a mechanical system based on an embedded pressure control device located inside the cylinder. A pre-set sub-atmospheric pressure must be achieved in the delivery manifold before flow is permitted from the cylinder.

W. K. Olander; M. Donatucci; J. Mayer; L. Wang

2000-01-01

392

Failed Operative Vaginal Delivery  

PubMed Central

Objective To compare maternal and neonatal outcomes in women undergoing a second stage cesarean after a trial of operative vaginal delivery with women undergoing a second stage cesarean without such an attempt. Methods This study is a secondary analysis of the women who underwent second stage cesarean. .The maternal outcomes examined included blood transfusion, endometritis, wound complication, anesthesia use, and maternal death. Infant outcomes examined included umbilical artery pH < 7.0, Apgar of 3 or less at 5 minutes, seizures within 24 hours of birth, hypoxic ischemic encephalopathy (HIE), stillbirth, skull fracture, and neonatal death. Results Of 3189 women who underwent second stage cesarean, operative vaginal delivery was attempted in 640. Labor characteristics were similar in the two groups with the exception of the admission to delivery time and cesarean indication. Those with an attempted operative vaginal delivery were more likely to undergo cesarean delivery for a non-reassuring fetal heart rate tracing (18.0% vs 13.9%, p=.01), have a wound complication (2.7% vs 1.0%; OR 2.65 95% CI 1.43–4.91), and require general anesthesia (8.0% vs 4.1%, OR 2.05 95% CI 1.44–2.91). Neonatal outcomes including umbilical artery pH less than 7.0, Apgar at or below 3 at 5 minutes, and hypoxic ischemic encephalopathy were more common for those with an attempted operative vaginal delivery. This was not significant when cases with a non-reassuring fetal heart rate tracing were removed. Conclusion Cesarean delivery after an attempt at operative vaginal delivery was not associated with adverse neonatal outcomes in the absence of a non-reassuring fetal heart rate tracin